SECOND EDITION
Edited by
Michael G. Gelder
Emeritus Professor of Psychiatry, 
Warneford Hospital, University of Oxford,Oxford, UK
Nancy C. Andreasen
Director, Mental Health Clinical Research Centre,University of Iowa Hospital and Clinic,Iowa City, USA
Juan J. López-Ibor Jr.
Professor of Psychiatry, Complutense University, Madrid, Spain
and
John R. Geddes
Professor of Epidemiological PsychiatryUniversity of Oxford, Warneford Hospital,Oxford, UKNew Oxford Textbook of 
Psychiatry
1VOLUME 1

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Preface to the second edition
This new edition, like the ﬁ  rst, aims to present a comprehensive 
account of clinical psychiatry with reference to its scientiﬁ  c basis 
and to the ill person’s perspective. As in the ﬁ  rst edition, the authors 
are drawn from many countries, including the UK, the USA, 12 countries in continental Europe, and Australasia. The favourable reception of the ﬁ  rst edition has led us to invite many of the 
original authors to revise their chapters for this second edition but 50 chapters are the work of new authors, many concerned with subjects that appeared in the ﬁ  rst edition, while others are com-
pletely new. The forensic psychiatry section has the most new chap-ters, followed by the section on psychology as a scientiﬁ  c basis of 
psychiatry.
The overall plan of the book resembles that of the ﬁ  rst edition 
(see preface to the 1st edition, reprinted on pages vii and viii). One 
important feature is that information about treatment appears in

important feature is that information about treatment appears in 
more than one place. The commonly used physical and psycho-logical treatments are described in Section 6. Their use in the treat-ment of any particular disorder is considered in the chapter con-cerned with that disorder and the account is in two parts. The ﬁ  rst 
part is a review of evidence about the effects of each of the treat-ments when used for that disorder. The second part, called Management, combines evidence from clinical trials with accumu-lated clinical experience to produce practical advice about the day to day care of people with the disorder.
Although much information can now be obtained from internet 
searches, textbooks are still needed to provide the comprehensive account of established knowledge into which new information can be ﬁ  tted and against which recent ﬁ  ndings can be evaluated.

searches, textbooks are still needed to provide the comprehensive account of established knowledge into which new information can be ﬁ  tted and against which recent ﬁ  ndings can be evaluated. 
As well as seeking to provide an authoritative account of essential knowledge, each chapter in the new edition includes a brief list of sources of further information, including where appropriate, regularly updated web sites.
An essential component of good practice is the need to be aware 
of patients’ perspectives, to respect their wishes, and to work with them, and often their families, as partners. The book opens with an important chapter on the experience of being a patient, and there are chapters on stigma, ethics, and the developing topic of values-based practice.
We are grateful to the following who advised us about parts 
of the book; Professor John Bancroft (Psychosexual Disorders), 
Professor T om Burns (Social and Community Psychiatry), Professor

Professor T om Burns (Social and Community Psychiatry), Professor 
William Fraser (Intellectual Disability), Professor Keith Hawton (Suicide and Deliberate Self Harm), Professor Susan Iversen (Psychology), Professor Robin Jacoby (Old Age Psychiatry), Professor Paul Mullen (Forensic Psychiatry), Sir Michael Rutter (Child and Adolescent Psychiatry), and Professor Gregory Stores (Sleep Disorders).
The editors

Preface to the ﬁ  rst edition
Three themes can be discerned in contemporary psychiatry: the 
growing unity of the subject, the pace of scientiﬁ  c advance, and the 
growth of practice in the community. We have sought to reﬂ  ect 
these themes in the New Oxford Textbook of Psychiatry  and to pres-
ent the state of psychiatry at the start of the new millennium. The book is written for psychiatrists engaged in continuous education and recertification; the previous, shorter, Oxford Textbook of 
Psychiatry  remains available for psychiatrists in training. The book 
is intended to be suitable also as a work of reference for psychia-trists of all levels of experience, and for other professionals whose work involves them in the problems of psychiatry.
The growing unity of psychiatry

The growing unity in psychiatry is evident in several ways. Biological and psychosocial approaches have been largely reconciled with a gen-eral recognition that genetic and environmental factors interact, and that psychological processes are based in and can inﬂ  uence neurobio-
logical mechanisms. At the same time, the common ground between the different psychodynamic theories has been recognized, and is widely accepted as more valuable than the differences between them.
The practice of psychiatry is increasingly similar in different 
countries, with the remaining variations related more to differences between national systems of health care and the resources available to clinicians, than to differences in the aims of the psychiatrists working in these countries. This unity of approach is reﬂ  ected in 
this book whose authors practise in many different countries and yet present a common approach. In this respect this textbook dif-

fers importantly from others which present the views of authors 
drawn predominantly from a single country or region.
Greater agreement about diagnosis and nosology has led to a 
better understanding of how different treatment approaches are effective in different disorders. The relative speciﬁ  city of psycho-
pharmacological treatments is being matched increasingly by the speciﬁ  city of some of the recently developed psychological treat-
ments, so that psychological treatment should no longer be applied without reference to diagnosis, as was sometimes done in the past.
The pace of scientiﬁ  c advance
Advances in genetics and in the neurosciences have already 
increased knowledge of the basic mechanisms of the brain and are beginning to uncover the neurobiological mechanisms involved in

increased knowledge of the basic mechanisms of the brain and are beginning to uncover the neurobiological mechanisms involved in 
psychiatric disorder. Striking progress has been achieved in the understanding of Alzheimer’s disease, for example, and there are indications that similar progress will follow in uncovering the causes of mood disorder, schizophrenia, and autism. Knowledge of genetics and the neurosciences is so extensive and the pace of change is so rapid that it is difﬁ  cult to present a complete account 
within the limited space available in a textbook of clinical psychiatry. We have selected aspects of these sciences that seem, to us and the authors, to have contributed signiﬁ  cantly to psychiatry or to be 
likely to do so before long.
Psychological and social sciences and epidemiology are essential

Psychological and social sciences and epidemiology are essential 
methods of investigation in psychiatry. Although the pace of advance in these sciences may not be as great as in the neurosciences, the findings generally have a more direct relation to clinical phenomena. Moreover, the mechanisms by which psychological and social factors interact with genetic, biochemical, and structural ones will continue to be important however great the progress in these other sciences. Among the advances in the psychological and social sciences that are relevant to clinical phenomena, we have included accounts of memory, psychological development, research on life events, and the effects of culture. Epidemiological studies continue to be crucial for deﬁ  ning psychiatric disorders, following 
their course, and identifying their causes.
Psychiatry in the community

In most countries, psychiatry is now practised in the community rather than in institutions, and where this change has yet be completed, it is generally recognized that it should take place. The change has done much more than transfer the locus of care; it has converted patients from passive recipients of care to active partici-pants with individual needs and preferences. Psychiatrists are now involved in the planning, provision, and evaluation of services for whole communities, which may include members of ethnic minor-ities, homeless people, and refugees. Responsibility for a commu-nity has underlined the importance of the prevention as well as the treatment of mental disorder and of the role of agencies other than health services in both. Care in the community has also drawn attention to the many people with psychiatric disorder who are treated in primary care, and has led to new ways of working between psychiatrists and physicians. At the same time, psychiatrists have

viii
worked more in general hospitals, helping patients with both 
medical and psychiatric problems. Others have provided care for offenders.
The organization of the book
In most ways, the organization of this book is along conventional lines. However, some matters require explanation.
Part 1 contains a variety of diverse topics brought together 
under the general heading of the subject matter and approach to psychiatry. Phenomenology, assessment, classiﬁ  cation, and ethical 
problems are included, together with the role of the psychiatrist as educator and as manager. Public health aspects of psychiatry are considered together with public attitudes to psychiatry and to psychiatric patients. Part 1 ends with a chapter on the links between science and practice. It begins with a topic that is central to good practice—the understanding of the experience of becoming a psychiatric patient.
Part 2 is concerned with the scientiﬁ  c foundations of psychiatry

Part 2 is concerned with the scientiﬁ  c foundations of psychiatry 
grouped under the headings neurosciences, genetics, psychological 
sciences, social sciences, and epidemiology. The chapters contain general information about these sciences; ﬁ  ndings speciﬁ  c to a 
particular disorder are described in the chapter on that disorder. Brain imaging techniques are discussed here because they link basic sciences with clinical research. As explained above, the chapters are selective and, in some, readers who wish to study the subjects in greater detail will ﬁ  nd suggestions for further reading.
Part 3 is concerned with dynamic approaches to psychiatry. The 
principal schools of thought are presented as alternative ways of understanding the inﬂ  uence of life experience on personality and

principal schools of thought are presented as alternative ways of understanding the inﬂ  uence of life experience on personality and 
on responses to stressful events and to illness. Some reference is made to dynamic psychotherapy in these accounts, but the main account of these treatments is in Part 6. This arrangement sepa-rates the chapters on the practice of dynamic psychotherapy from those on psychodynamic theory, but we consider that this disad-vantage is outweighed by the beneﬁ  t of considering together the 
commonly used forms of psychotherapy.
Part 4 is long, with chapters on the clinical syndromes of adult

Part 4 is long, with chapters on the clinical syndromes of adult 
psychiatry, with the exception of somatoform disorders which appear in Part 5, Psychiatry and Medicine. This latter contains more than a traditional account of psychosomatic medicine. It also includes a review of psychiatric disorders that may cause medical symptoms unexplained by physical pathology, the medical, surgi-cal, gynaecological, and obstetric conditions most often associated with psychiatric disorder, health psychology, and the treatment of psychiatric disorder in medically ill patients.
Information about treatment appears in more than one part 
of the book. Part 6 contains descriptions of the physical and

of the book. Part 6 contains descriptions of the physical and 
psychological treatments in common use in psychiatry. Dynamic psychotherapy and psychoanalysis are described alongside counselling and cognitive behavioural techniques. This part of the book contains general descriptions of the treatments; their use for a particular disorder is considered in the chapter on that disorder. In the latter, the account is generally in two parts: a review of 
evidence about the efﬁ  cacy of the treatment, followed by advice 
on man agement in which available evidence is supplemented, where necessary, with clinical experience. Treatment methods designed specially for children and adolescents, for people with mental retardation (learning disability), and for patients within the forensic services are considered in Parts 9, 10, and 11 
respectively.
Social psychiatry and service provision are described in Part 7.

Social psychiatry and service provision are described in Part 7. 
Public policy issues, as well as the planning, delivery, and evalua-tion of services, are discussed here. Psychiatry in primary care is an important topic in this part of the book. There are chapters on the special problems of members of ethnic minorities, homeless people, and refugees, and the effects of culture on the provision and uptake of services.
Child and adolescent psychiatry, old age psychiatry, and mental

retardation are described in Parts 8, 9, and 10. These accounts are less detailed than might be found in textbooks intended for specialists working exclusively in the relevant subspecialty. Rather, they are written for readers experienced in another branch of psy-chiatry who wish to improve their knowledge of the special subject. We are aware of the controversy surrounding our choice of the title of Part 10. We have selected the term ‘mental retardation’ because it is used in both ICD-10 and DSM-IV . In some countries this term has been replaced by another that is thought to be less stigmatizing and more acceptable to patients and families. For example, in the United Kingdom the preferred term is ‘learning disability’ . While we sympathize with the aims of those who adopt this and other alternative terms, the book is intended for an international reader-ship and it seems best to use the term chosen by the World Health Organization as most generally understood. Thus the term mental

retardation is used unless there is a special reason to use another.
In Part 11, Forensic Psychiatry, it has been especially difﬁ  cult to 
present a general account of the subject that is not tied to practice in a single country. This is because systems of law differ between countries and the practice of forensic psychiatry has to conform with the local legal system. Although many of the examples in this part of the book may at ﬁ  rst seem restricted in their relevance 
because they are described in the context of English law, we hope 
that readers will be able to transfer the principles described in these chapters to the legal tradition in which they work.
Finally, readers should note that the history of psychiatry is pre-

sented in more than one part of the book. The history of psychiatry as a medical specialty is described in Part 1. The history of ideas about the various psychiatric disorders appears, where relevant, in the chapters on these disorders, where they can be considered in relation to present-day concepts. The history of ideas about aetiology is considered in Part 2, which covers the scientiﬁ  c basis of 
psychiatric aetiology, while the historical development of dynamic psychiatry is described in Part 3.
Michael Gelder
Juan López-Ibor
Nancy Andreasen
preface

Acknowledgements from the 
ﬁ rst edition
We are grateful to the many colleagues who have advised us about 
certain parts of the book.
The following helped us to plan specialized parts of the book: 
Dr Jeremy Holmes (Section 3, Psychodynamic Contributions to Psychiatry); Professor Richard Mayou (Section 5, Psychiatry and Medicine); Professor Robin Jacoby (Section 8, Psychiatry of Old Age); Sir Michael Rutter (Section 9, Child and Adolescent Psychiatry); Professor William Fraser (Section 10,  Intellectual Disablity); Professor Robert Bluglass (Section 11, Forensic Psychiatry).
The following helped us to plan certain sections within Section 4, 
General Psychiatry: Professor Alwyn Lishman (delirium, dementia, amnestic syndrome, and other cognitive disorders); Professor Grifﬁ  th Edwards (alcohol use disorders); Dr Philip Robson (other substance use disorders); Professor Guy Goodwin (mood disorders);

Professor John Bancroft (sexuality, gender identity, and their disorders); Professor Gregory Stores (sleep–wake disorders); Professor Keith Hawton (suicide and attempted suicide). In Section 6, 
Professor Philip Cowen advised about somatic treatments, 
Dr Jeremy Holmes about psychodynamic treatments, and Professor David Clark about cognitive behavioural therapy. Dr Max Marshall provided helpful advice about forensic issues for Section 7. We also thank the many other colleagues whose helpful suggestions about speciﬁ  c problems aided the planning of the 
book.
Finally, we record our special gratitude to the authors and to the 
staff of Oxford University Press.

Contents
Volume 1
  Preface to the second edition  v
  Preface to the ﬁ  rst edition  vii
  Acknowledgements from the ﬁ  rst edition  ix
  Contributors list  xxi
Section 1 The Subject Matter 
of and Approach to Psychiatry
 1.1 The patient’s perspective  3
Kay Redﬁ  eld Jamison, Richard Jed 
Wyatt, and Adam Ian Kaplin
 1.2 Public attitudes and the challenge of stigma  5
Graham Thornicroft, Elaine Brohan, and Aliya Kassam
 1.3 Psychiatry as a worldwide 
public health problem  10
 1.3.1 Mental disorders as a worldwide 
public health issue  10
Benedetto Saraceno
 1.3.2 Transcultural psychiatry  13
Julian Leff
 1.4 The history of psychiatry as a 
medical specialty  17
Pierre Pichot
 1.5 Ethics and values   28
 1.5.1 Psychiatric ethics  28
Sidney Bloch and Stephen Green
 1.5.2 Values and values-based practice 
in clinical psychiatry  32
K. W. M. Fulford
 1.6 The psychiatrist as a manager  39
Juan J. López-Ibor Jr. and Costas Stefanis 1.7 Descriptive phenomenology  47
Andrew Sims

 1.8 Assessment  62
 1.8.1 The principles of clinical assessment in general psychiatry  
62
John E. Cooper and Margaret Oates
 1.8.2 Assessment of personality  78
C. Robert Cloninger
 1.8.3 Cognitive assessment  85
Graham E. Powell
 1.8.4 Questionnaire, rating, and behavioural methods of assessment  
94
John N. Hall
 1.9 Diagnosis and classiﬁ  cation  99
Michael B. First and Harold Alan Pincus
 1.10 From science to practice  122
Section 2  The Scientiﬁ  c Basis 
of Psychiatric Aetiology
 2.1 Brain and mind  133
Martin Davies
 2.2 Statistics and the design of experiments 
and surveys  137
Graham Dunn
 2.3 The contribution of neurosciences  144
  2.3.1 Neuroanatomy  144
R. C. A. Pearson
  2.3.2 Neurodevelopment  156
Karl Zilles
  2.3.3 Neuroendocrinology  160
Charles B. Nemeroff and Gretchen N. Neigh

xii
  2.3.4 Neurotransmitters and signalling  168
Trevor Sharp
  2.3.5 Neuropathology  177
Peter Falkai and Bernhard Bogerts
  2.3.6 Functional position emission 
tomography in psychiatry  185
P . M. Grasby
  2.3.7 Structural magnetic resonance imaging  
191
J. Suckling and E. T. Bullmore
  2.3.8 Functional magnetic resonance imaging  196
E. T. Bullmore and J. Suckling
  2.3.9 Neuronal networks, epilepsy, and other brain dysfunctions  
201
John G. R. Jefferys
 2.3.10 Psychoneuroimmunology  205
Robert Dantzer and Keith W. Kelley
 2.4 The contribution of genetics  212
 2.4.1 Quantitative genetics  212
Anita Thapar and Peter McGufﬁ  n
 2.4.2 Molecular genetics  222
Jonathan Flint
 2.5 The contribution of psychological science   234
 2.5.1 Development psychology through infancy, childhood, and adolescence  
234
William Yule and Matt Woolgar
 2.5.2 Psychology of attention  245
Elizabeth Coulthard and Masud Husain
 2.5.3 Psychology and biology of memory  249

234
Andreas Meyer-Lindenberg and Terry E. Goldberg
 2.5.4 The anatomy of human emotion  257
R. J. Dolan
 2.5.5 Neuropsychological basis of neuropsychiatry  
262
L. Clark, B. J. Sahakian, and T. W. Robbins
 2.6 The contribution of social sciences   268
 2.6.1 Medical sociology and issues of aetiology  268
George W. Brown
 2.6.2 Social and cultural anthropology: salience for psychiatry  
275
Arthur Kleinman
 2.7 The contribution of epidemiology 
to psychiatric aetiology  280
Scott HendersonSection 3  Psychodynamic 
Contributions to Psychiatry
 3.1 Psychoanalysis: Freud’s theories and their 
contemporary development  293
Otto F. Kernberg
 3.2 Object relations, attachment theory, self-psychology, and interpersonal psychoanalysis  
306
Jeremy Holmes
 3.3 Current psychodynamic approaches to psychiatry  
313
Glen O. Gabbard

3.2 Object relations, attachment theory, self-psychology, and interpersonal psychoanalysis  
306
313
Section 4  Clinical Syndromes 
of Adult Psychiatry
 4.1 Delirium, dementia, amnesia, and 
other cognitive disorders   325
 4.1.1 Delirium   325
David Meagher and Paula Trzepacz
 4.1.2 Dementia: Alzheimer’s disease   333
Simon Lovestone
 4.1.3 Frontotemporal dementias  344
Lars Gustafson and Arne Brun
 4.1.4 Prion disease  351
John Collinge
 4.1.5 Dementia with Lewy bodies  361
I. G. McKeith
 4.1.6 Dementia in Parkinson’s disease  368
R. H. S. Mindham and T. A. Hughes
 4.1.7 Dementia due to Huntington’s disease  371
Susan Folstein and Russell L. Margolis
 4.1.8 Vascular dementia  375
Timo Erkinjuntti
 4.1.9 Dementia due to HIV disease  384
Mario Maj
 4.1.10 The neuropsychiatry of head injury  387
Simon Fleminger
 4.1.11 Alcohol-related dementia (alcohol-induced

Mario Maj
 4.1.11 Alcohol-related dementia (alcohol-induced 
dementia; alcohol-related brain damage)  399
Jane Marshall
 4.1.12 Amnesic syndromes  403
Michael D. Kopelman
 4.1.13 The management of dementia  411
John-Paul Taylor and Simon Fleminger
 4.1.14 Remediation of memory disorders  419
Jonathan J. Evanscontents

xiii
 4.2 Substance use disorders  426
 4.2.1 Pharmacological and psychological 
aspects of drugs abuse  426
David J. Nutt and Fergus D. Law
 4.2.2 Alcohol use disorders  432
 4.2.2.1 Aetiology of alcohol problems   432
Juan C. Negrete and Kathryn J. Gill
 4.2.2.2 Alcohol dependence and alcohol problems   437
 4.2.2.3 Alcohol and psychiatric and physical disorders   442
Karl F. Mann and Falk Kiefer
 4.2.2.4 Treatment of alcohol dependence   447
Jonathan Chick
 4.2.2.5 Services for alcohol use disorders   459
D. Colin Drummond
 4.2.2.6 Prevention of alcohol-related problems   467
Robin Room
 4.2.3 Other substance use disorders  472
 4.2.3.1 Opioids: heroin, methadone, and 
buprenorphine   473
Soraya Mayet, Adam R. Winstock, and John Strang
 4.2.3.2 Disorders relating to the use of 
amphetamine and cocaine   482
Nicholas Seivewright and Robert Fung
 4.2.3.3 Disorders relating to use of PCP 
and hallucinogens   486
Henry David Abraham
 4.2.3.4 Misuse of benzodiazepines   490

Sarah Welch and Michael Farrell
 4.2.3.5 Disorders relating to the use of ecstasy 
and other ‘party drugs ’  494
Adam R. Winstock and Fabrizio Schifano
 4.2.3.6 Disorders relating to the use of 
volatile substances   502
Richard Ives
 4.2.3.7 The mental health effects of cannabis use   507
Wayne Hall
 4.2.3.8 Nicotine dependence and treatment   510
Ma Inés López-Ibor
 4.2.4 Assessing need and organizing services 
for drug misuse problems  515
John Marsden, Colin Bradbury, and John Strang
 4.3 Schizophrenia and acute transient 
psychotic disorders  521
 4.3.1 Schizophrenia: a conceptual history  521
 4.3.2 Descriptive clinical features of schizophrenia  526
Peter F. Liddle
 4.3.3 The clinical neuropsychology of schizophrenia  531
Philip D. Harvey and Christopher R. Bowie

 4.3.4 Diagnosis, classiﬁ  cation, and differential 
diagnosis of schizophrenia  534
Anthony S. David 4.3.5 Epidemiology of schizophrenia  540
Assen Jablensky
 4.3.6 Aetiology  553
 4.3.6.1 Genetic and environmental risk 
factors for schizophrenia   553
R. M. Murray and D. J. Castle
 4.3.6.2 The neurobiology of schizophrenia   561
Paul J. Harrison
 4.3.7 Course and outcome of schizophrenia 
and their prediction  568
 4.3.8 Treatment and management of schizophrenia  
578
D. G. Cunningham Owens and E. C. Johnstone
 4.3.9 Schizoaffective and schizotypal disorders  595
Ming T. Tsuang, William S. Stone, and 
Stephen V. Faraone
 4.3.10 Acute and transient psychotic disorders  602
J. Garrabé and F.-R. Cousin
 4.4 Persistent delusional symptoms 
and disorders  609
Alistair Munro

 4.5 Mood disorders  629
 4.5.1 Introduction to mood disorders  629
  4.5.2 Clinical features of mood 
disorders and mania  632
Per Bech
  4.5.3 Diagnosis, classiﬁ  cation, and differential diagnosis of the mood disorders  
637
Gordon Parker
  4.5.4 Epidemiology of mood disorders  645
Peter R. Joyce
 4.5.5 Genetic aetiology of mood disorders  650
Pierre Oswald, Daniel Souery, and Julien Mendlewicz
 4.5.6 Neurobiological aetiology of mood disorders  658
Guy Goodwin
  4.5.7 Course and prognosis of mood disorders  665
Jules Angst
  4.5.8 Treatment of mood disorders  669
E. S. Paykel and J. Scott
  4.5.9 Dysthymia, cyclothymia, and hyperthymia  680
Hagop S. Akiskal
 4.6 Stress-related and adjustment disorders  693
  4.6.1 Acute stress reactions  693
Anke Ehlers, Allison G. Harvey and Richard A. Bryant

  4.6.2 Post-traumatic stress disorder  700
Anke Ehlerscontents

xiv
  4.6.3 Recovered memories and false memories  713
Chris R. Brewin
  4.6.4 Adjustment disorders  716
James J. Strain, Kimberly Klipstein, and 
Jeffrey Newcorm
  4.6.5 Bereavement  724
Beverley Raphael, Sally Wooding, and Julie Dunsmore
 4.7 Anxiety disorders  729
4.7.1 Generalized anxiety disorders   729
Stella Bitran, David H. Barlow, and David A. Spiegel
4.7.2  Social anxiety disorder and speciﬁ  c
phobias   739
Michelle A. Blackmore, Brigette A. Erwin, 
Richard G. Heimberg, Leanne Magee, and David M. Fresco
4.7.3 Panic disorder and agoraphobia   750
James C. Ballenger
 4.8 Obsessive–compulsive disorder  765
Joseph Zohar, Leah Fostick, and Elizabeth
Juven-Wetzler
 4.9 Depersonalization disorder  774
Nick Medford, Mauricio Sierra, and Anthony S. David
 4.10 Disorders of eating  777
 4.10.1 Anorexia nervosa  777
Gerald Russell
 4.10.2 Bulimia nervosa  800
Christopher G. Fairburn, 
Zafra Cooper, and Rebecca Murphy
 4.11 Sexuality, gender identity, and their
disorders  812

4.10.1 Anorexia nervosa  777
 4.11.1 Normal sexual function  812
Roy J. Levin
 4.11.2 The sexual dysfunctions  821
Cynthia A. Graham and John Bancroft
 4.11.3 The paraphilias  832
J. Paul Fedoroff
 4.11.4 Gender identity disorder in adults  842
Richard Green
 4.12 Personality disorders  847
 4.12.1 Personality disorders: an 
introductory perspective  847
 4.12.2 Diagnosis and classiﬁ  cation of personality disorders  
855
James Reich and Giovanni de Girolamo 4.12.3 Speciﬁ  c types of personality disorder  861
Jos´e Luis Carrasco and Dusica Lecic-Tosevski
 4.12.4 Epidemiology of personality disorders  881
Francesca Guzzetta and Giovanni de Girolamo
 4.12.5 Neuropsychological templates for 
abnormal personalities: from genes to biodevelopmental pathways  
886
Adolf Tobeña

886
 4.12.6 Psychotherapy for personality disorder  892
Anthony W. Bateman and Peter Fonagy
 4.12.7 Management of personality disorder  901
Giles Newton-Howes and Kate Davidson
 4.13 Habit and impulse control disorders  911
 4.13.1 Impulse control disorders  911
Susan L. McElroy and Paul E. Keck Jr.
 4.13.2 Special psychiatric problems relating to gambling  
919
Emanuel Moran
 4.14 Sleep–wake disorders  924
 4.14.1 Basic aspects of sleep–wake disorders  924
Gregory Stores
 4.14.2 Insomnias  933
Colin A. Espie and Delwyn J. Bartlett
 4.14.3 Excessive sleepiness  938
Michel Billiard
 4.14.4 Parasomnias  943
Carlos H. Schenck and Mark W. Mahowald
 4.15 Suicide  951
 4.15.1 Epidemiology and causes of suicide  951
Jouko K. Lonnqvist
 4.15.2 Deliberate self-harm: epidemiology and risk factors  
957

957
Ella Arensman and Ad J. F. M. Kerkhof
 4.15.3 Biological aspects of suicidal behaviour  963
J. John Mann and Dianne Currier
 4.15.4 Treatment of suicide attempters and prevention of suicide and attempted suicide  
969
Keith Hawton and Tatiana Taylor
 4.16 Culture-related speciﬁ  c psychiatric 
syndromes  979
Wen-Shing Tseng
  Indexcontents

Preface to the second edition  v
  Acknowledgements  ix
Section 5  Psychiatry and Medicine
 5.1 Mind–body dualism, psychiatry, 
and medicine  989
Michael Sharpe and Jane Walker
 5.2 Somatoform disorders and other causes of medically unexplained symptoms  
992
 5.2.1 Somatoform disorders and 
functional symptoms  992
Richard Mayou
 5.2.2 Epidemiology of somatoform disorders and other causes of unexplained medical symptoms  
995
Gregory Simon
 5.2.3 Somatization disorder and related disorders  999
Per Fink
 5.2.4 Conversion and dissociation disorders  1011
Christopher Bass
 5.2.5 Hypochondriasis (health anxiety)  1021
Russell Noyes Jr.
 5.2.6 Pain disorder  1029
Sidney Benjamin and Stella Morris
 5.2.7 Chronic fatigue syndrome  1035
Michael Sharpe and Simon Wessely
 5.2.8 Body dysmorphic disorder  1043
Katharine A. Phillips
 5.2.9 Factitious disorder and malingering  1049

5.2.7 Chronic fatigue syndrome  1035
Christopher Bass and David Gill 5.2.10 Neurasthenia  1059
Felice Lieh Mak
 5.3 Medical and surgical conditions 
and treatments associated with psychiatric disorders  
1065
 5.3.1 Adjustment to illness and handicap  1065
Allan House
 5.3.2 Psychiatric aspects of 
neurological disease  1071
Maria A. Ron
 5.3.3 Epilepsy  1076
Brian Toone
 5.3.4 Medical conditions associated with psychiatric disorder   
1081
James R. Rundell
 5.3.5 Psychiatric aspects of infections  1090
José-Luis Ayuso-Mateos
 5.3.6 Psychiatric aspects of surgery (including transplantation)  
1096
S. A. Hales, S. E. Abbey, and G. M. Rodin
 5.3.7 Psychiatric aspects of cancer  1100
Jimmie C. Holland and Jessica Stiles
 5.3.8 Psychiatric aspects of accidents, burns, and other physical trauma  
1105
Ulrik Fredrik Malt

5.3.7 Psychiatric aspects of cancer  1100
1105
 5.4 Obstetric and gynaecological conditions 
associated with psychiatric disorder  1114
Ian Brockington
 5.5 Management of psychiatric disorders in medically ill patients, including emergencies  
1128
Pier Maria Furlan and Luca OstacoliContents
Volume 2

xvi
 5.6 Health psychology  1135
John Weinman and Keith J. Petrie
 5.7 The organization of psychiatric services 
for general hospital departments  1144
Frits J. Huyse, Roger G. Kathol, 
Wolfgang Söllner, and Lawson Wulsin
Section 6  Treatment 
Methods in Psychiatry
 6.1 The evaluation of treatments  1151
 6.1.1 The evaluation of physical treatments  1151
Clive E. Adams
 6.1.2 The evaluation of psychological treatment  1158
Paul Crits-Christoph and 
Mary Beth Connolly Gibbons
 6.2 Somatic treatments  1168
 6.2.1 General principles of drug 
therapy in psychiatry  1168
J. K. Aronson
 6.2.2 Anxiolytics and hypnotics  1178
Malcolm Lader
 6.2.3 Antidepressants  1185
Zubin Bhagwagar and George R. Heninger
 6.2.4 Lithium and related mood stabilizers  1198
Robert M. Post
 6.2.5 Antipsychotic and anticholinergic drugs  1208
Herbert Y. Meltzer and William V. Bobo
 6.2.6 Antiepileptic drugs  1231
Brian P . Brennan and Harrison G. Pope Jr.
 6.2.7 Drugs for cognitive disorders  1240
Leslie Iversen

 6.2.8 Drugs used in the treatment of the addictions  
1242
Fergus D. Law and David J. Nutt
 6.2.9 Complementary medicines  1247
Ursula Werneke
 6.2.10 Non-pharmacological somatic treatments  1251
6.2.10.1 Electroconvulsive therapy   1251
Max Fink
6.2.10.2 Phototherapy   1260
Philip J. Cowen
6.2.10.3 Transcranial magnetic stimulation   1263
Declan McLoughlin and Andrew Mogg
6.2.10.4 Neurosurgery for psychiatric disorders   1266
Keith Matthews and David Christmas
 6.3 Psychological treatments  1272
 6.3.1 Counselling  1272
Diana Sanders 6.3.2 Cognitive behaviour therapy  1285
 6.3.2.1 Cognitive behaviour therapy for 
anxiety disorders   1285
David M. Clark
 6.3.2.2 Cognitive behaviour therapy for 
eating disorders   1298
Zafra Cooper, Rebecca Murphy, and 
Christopher G. Fairburn

 6.3.2.3 Cognitive behaviour therapy for 
depressive disorders   1304
Melanie J. V. Fennell
 6.3.2.4 Cognitive behaviour therapy 
for schizophrenia   1313
Max Birchwood and Elizabeth Spencer
 6.3.3  Interpersonal psychotherapy for 
depression and other disorders  1318
Carlos Blanco, John C. Markowitz, 
and Myrna M. Weissman
 6.3.4  Brief individual psychodynamic 
psychotherapy  1327
Amy M. Ursano and Robert J. Ursano
 6.3.5  Psychoanalysis and other long-term dynamic psychotherapies  
1337
Peter Fonagy and Horst Kächele
 6.3.6  Group methods in adult psychiatry  1350
John Schlapobersky and Malcolm Pines
 6.3.7  Psychotherapy with couples  1369
Michael Crowe
 6.3.8  Family therapy in the adult psychiatric setting  
1380
Sidney Bloch and Edwin Harari
 6.3.9 Therapeutic communities  1391
David Kennard and Rex Haigh

1380
 6.4 Treatment by other professions  1399
 6.4.1  Rehabilitation techniques  1399
W. Rössler
 6.4.2  Psychiatric nursing techniques  1403
Kevin Gournay
 6.4.3  Social work approaches to mental health work: international trends  
1408
Shulamit Ramon
 6.4.4  Art therapy  1413
Diane Waller
 6.5 Indigenous, folk healing practices  1418
Section 7  Social Psychiatry 
and Service Provision
 7.1 Public policy and mental health  1425
Matt Muijen and Andrew McCullochcontents

xvii
 7.2 Service needs of individuals and populations  1432
Mike Slade, Michele Tansella, and Graham Thornicroft
 7.3 Cultural differences care pathways, service use, 
and outcome  1438
Jim van Os and Kwame McKenzie
 7.4 Primary prevention of mental disorders  1446
J. M. Bertolote
 7.5 Planning and providing mental health services for a community  
1452
Tom Burns
 7.6 Evaluation of mental health services  1463
Michele Tansella and Graham Thornicroft
 7.7 Economic analysis of mental health services  1473
Martin Knapp and Dan Chisholm
 7.8 Psychiatry in primary care  1480
David Goldberg, André Tylee, and Paul Walters
 7.9 The role of the voluntary sector  1490
Vanessa Pinfold and Mary Teasdale
 7.10 Special problems  1493
7.10.1 The special psychiatric problems of refugees  1493
Richard F. Mollica, Melissa A. Culhane, 
and Daniel H. Hovelson
7.10.2 Mental health services for homeless 
mentally ill people  1500
Tom K. J. Craig 
7.10.3 Mental health services for ethnic minorities  1502

Tom K. J. Craig and Dinesh Bhugra 
Section 8  The Psychiatry of Old Age
 8.1 The biology of ageing  1507
Alan H. Bittles
 8.2 Sociology of normal ageing  1512
Sarah Harper
 8.3 The ageing population and the epidemiology 
of mental disorders among the elderly  1517
Scott Henderson and Laura Fratiglioni
 8.4 Assessment of mental disorder in older patients  
1524
Robin Jacoby
 8.5 Special features of clinical syndromes in the elderly  
1530
 8.5.1 Delirium in the elderly  1530
James Lindesay
 8.5.1.1 Mild cognitive impairment   1534
Claudia Jacova and Howard H. Feldman 8.5.2 Substance use disorders in older people  1540
Henry O’Connell and Brian Lawlor
 8.5.3 Schizophrenia and paranoid 
disorders in late life  1546
Barton W. Palmer, Gauri N. Savla, 
and Thomas W. Meeks
 8.5.4 Mood disorders in the elderly  1550

Robert Baldwin
 8.5.5 Stress-related, anxiety, and obsessional 
disorders in elderly people  1558
 8.5.6 Personality disorders in the elderly  1561
Suzanne Holroyd
 8.5.7 Suicide and deliberate self-harm in elderly people  
1564
 8.5.8 Sex in old age  1567
John Kellett and Catherine Oppenheimer
 8.6 Special features of psychiatric 
treatment for the elderly  1571
Catherine Oppenheimer
 8.7 The planning and organization of services for older adults  
1579
Pamela S. Melding
Section 9  Child and 
Adolescent Psychiatry
 9.1 General issues   1589
 9.1.1 Developmental psychopathology and 
classiﬁ  cation in childhood and adolescence  
1589
Stephen Scott
 9.1.2 Epidemiology of psychiatric disorder in childhood and adolescence  
1594
E. Jane Costello and Adrian Angold

1589
1594
 9.1.3 Assessment in child and adolescent psychiatry  
1600
Jeff Bostic and Andrés Martin
 9.1.4 Prevention of mental disorder in childhood and other public health issues  
1606
Rhoshel Lenroot
 9.2 Clinical syndromes   1612
 9.2.1 Neuropsychiatric disorders  1612
James C. Harris
 9.2.2 Speciﬁ  c developmental disorders in 
childhood and adolescence  1622
Helmut Remschmidt and 
Gerd Schulte-Körnecontents

xviii
  9.2.3 Autism and the pervasive 
developmental disorders  1633
Fred R. Volkmar and Ami Klin
  9.2.4 Attention deﬁ  cit and hyperkinetic disorders in childhood and adolescence  
1643
Eric Taylor
  9.2.5 Conduct disorders in childhood and adolescence  
1654
  9.2.6 Anxiety disorders in childhood and adolescence  
1664
Daniel S. Pine
  9.2.7 Paediatric mood disorders  1669
David Brent and Boris Birmaher
  9.2.8 Obsessive–compulsive disorder and tics in children and adolescents  
1680
Martine F. Flament and Philippe Robaey
  9.2.9 Sleep disorders in children and adolescents  
1693
 9.2.10 Suicide and attempted suicide in children and adolescents  
1702
David Shaffer, Cynthia R. Pfeffer, and 
Jennifer Gutstein
 9.2.11 Children’s speech and 
language difﬁ  culties  1710
Judy Clegg
 9.2.12 Gender identity disorder in children and adolescents  
1718
 9.3 Situations affecting child mental health   1724
 9.3.1 The inﬂ  uence of family, school,

Judy Clegg
1718
 9.3.1 The inﬂ  uence of family, school, 
and the environment  1724
Barbara Maughan
 9.3.2 Child trauma  1728
David Trickey and Dora Black
 9.3.3 Child abuse and neglect  1731
David P . H. Jones
 9.3.4 The relationship between physical and mental health in children and adolescents  
1740
Julia Gledhill and M. Elena Garralda
 9.3.5 The effects on child and adult mental health of adoption and foster care  
1747
June Thoburn
 9.3.6 Effects of parental psychiatric and physcial illness on child development  
1752
Paul Ramchandani, Alan Stein, and Lynne Murray 9.3.7 The effects of bereavement in childhood  1758
Dora Black and David Trickey
 9.4 The child as witness  1761
Anne E. Thompson and John B. Pearce
 9.5 Treatment methods for children 
and adolescents   1764
 9.5.1 Counselling and psychotherapy 
for children  1764
John B. Pearce

9.4 The child as witness  1761
 9.5.2 Psychodynamic child psychotherapy   1769
Peter Fonagy and Mary Target
 9.5.3 Cognitive behaviour therapies for children and families  
1777
Philip Graham
 9.5.4 Caregiver-mediated interventions for children and families   
1787
Philip A. Fisher and Elizabeth A. Stormshak
 9.5.5 Medication for children and adolescents: current issues   
1793
Paramala J. Santosh
 9.5.6 Residential care for social reasons  1799
Leslie Hicks and Ian Sinclair
 9.5.7 Organization of services for children and adolescents with mental health problems  
1802
Miranda Wolpert
 9.5.8 The management of child and adolescent psychiatric emergencies  
1807
Gillian Forrest
 9.5.9 The child psychiatrist as consultant to schools and colleges  
1811
Simon G. Gowers and Sian Thomas
Section 10  Intellectual Disability

1807
1811
Section 10  Intellectual Disability 
(Mental Retardation)
 10.1  Classiﬁ  cation, diagnosis, psychiatric 
assessment, and needs assessment  1819
A. J. Holland
 10.2  Prevalence of intellectual disabilities and epidemiology of mental ill-health in adults with intellectual disabilities  
1825
Sally-Ann Cooper and Elita Smiley
 10.3  Aetiology of intellectual disability: general issues and prevention  
1830
Markus Kaski
 10.4  Syndromes causing intellectual disability  1838
David M. Clarke and Shoumitro Debcontents

xix
 10.5  Psychiatric and behaviour disorders 
among mentally retarded people  1849
 10.5.1 Psychiatric and behaviour disorders among 
children and adolescents with intellectual disability  
1849
Bruce J. Tonge
 10.5.2 Psychiatric and behaviour disorders among adult persons with intellectual disability  
1854
Anton Došen
 10.5.3 Epilepsy and epilepsy-related behaviour disorders among people with intellectual disability  
1860
Matti Iivanainen
 10.6 Methods of treatment  1871
T. P. Berney
 10.7  Special needs of adolescents and elderly 
people with intellectual disability  1878
Jane Hubert and Sheila Hollins
 10.8  Families with a member with intellectual disability and their needs  
1883
Ann Gath and Jane McCarthy
 10.9  The planning and provision of psychiatric services for adults with intellectual disability  
1887
Nick Bouras and Geraldine Holt
Section 11  Forensic Psychiatry
 11.1 General principles of law relating to people with mental disorder  
1895
Michael Gunn and Kay Wheat

1887
1895
 11.2 Psychosocial causes of offending  1908
David P . Farrington
 11.3 Associations between psychiatric disorder and offending  
1917
 11.3.1 Associations between psychiatric 
disorder and offending  1917
Lindsay Thomson and Rajan Darjee
 11.3.2 Offending, substance misuse, and mental disorder  
1926
Andrew Johns
 11.3.3 Cognitive disorders, epilepsy, ADHD, and offending  
1928
Norbert Nedopil 11.4 Mental disorders among offenders 
in correctional settings  1933
James R. P . Ogloff
 11.5 Homicide offenders including mass murder and infanticide  
1937
Nicola Swinson and Jennifer Shaw
 11.6 Fraud, deception, and thieves  1941
David V. James
 11.7 Juvenile delinquency and serious antisocial behaviour  
1945
Susan Bailey
 11.8 Child molesters and other sex offenders  
1960
Stephen Hucker

1945
1960
 11.9 Arson (ﬁ  re-raising)  1965
Herschel Prins
 11.10 Stalking  1970
Paul E. Mullen
 11.11 Querulous behaviour: vexatious litigation, 
abnormally persistent complaining and petitioning  
1977
 11.12 Domestic violence  1981
Gillian C. Mezey
 11.13 The impact of criminal victimization  1984
Gillian C. Mezey and lan Robbins
 11.14 Assessing and managing the risks of violence towards others  
1991
Paul E. Mullen and James R. P . Ogloff
 11.15  The expert witness in the  Criminal Court: assessment, reports, and testimony  
2003
John O’Grady
 11.16 Managing offenders with psychiatric disorders in general psychiatric sevices  
2009
 11.17 Management of offenders with mental disorder in specialist forensic mental health services  
2015
Pamela J. Taylor and Emma Dunn
  Index  contents

Contributors list
S.E.  Abbey  Associate Professor of Psychiatry, University of T oronto, 
T oronto, Canada
Chapter 5.3.6
Henry David Abraham  Distinguished Life Fellow, American Psychiatric 
Association
Chapter 4.2.3.3
Clive E. Adams  Cochrane Schizophrenia Group, University of Oxford 
Department of Psychiatry, Warneford Hospital, Oxford, UK
Chapter 6.1.1
Hagop S. Akiskal  Professor of Psychiatry and Director of the International 
Mood Center, University of California at San Diego, California, USA
Chapter 4.5.9
Nancy C. Andreasen  Dept of Psychiatry, University of Iowa Hospitals & 
Clinics, Iowa City, USA 
Chapter 4.3.1
Adrian Angold  Associate Professor of Child and Adolescent 
Psychiatry, Duke University Medical Center, Durham, North Carolina, USA
Chapter 9.1.2
Jules Angst Emeritus Professor of Psychiatry, Zurich University
Chapter 4.5.7
Ella Arensman Director of Research, National Suicide Research Foundation, 
Ireland
Chapter 4.15.2

Ireland
J.K. Aronson Reader in Clinical Pharmacology, University Department of 
Primary Health Care, Headington, Oxford
Chapter 6.2.1
José-Luis Ayuso-Mateos  Chairman, Department of Psychiatry, Universidad 
Autónoma de Madrid, Hospital Universitario de la Princesa, Spain
Chapter 5.3.5
Susan Bailey  Consultant Child and Adolescent Forensic Psychiatrist, 
Salford NHS Trust and Maudsley NHS Trust; Senior Research Fellow, University of Manchester, UK
Chapter 11.7
Robert Baldwin  Consultant, Old Age Psychiatrist, and Honorary Senior 
Lecturer, Manchester Royal Inﬁ  rmary, UK
Chapter 8.5.4James C. Ballenger Retired Professor and Chairman, Department of 
Psychiatry and Behavioral Sciences and Director, Institute of Psychiatry, Medical University of South Carolina
Chapter 4.7.3

John Bancroft , The Kinsey Institute for Research in Sex, Gender, & 
Reproduction and Department of Psychiatry, University of Oxford
Chapter 4.11.2
David H. Barlow  Center for Anxiety and Related Disorders at Boston 
University, Massachusetts, USA
Chapter 4.7.1
Delwyn J. Bartlett Woolcock Institute of Medical Research, Sydney, Australia 
Chapter 4.14.2
Christopher Bass  Consultant in Liaison Psychiatry, John Radcliffe 
Hospital, Oxford, UK
Chapters 5.2.4 and 5.2.9
Antony W. Bateman  Halliwick Psychotherapy Dept, St Ann’s Hospital, 
London, UK 
Chapter 4.12.6
Per Bech  Professor of Psychiatry and Head of Psychiatric Research 
Unit, WHO Collaborating Centre, Frederiksborg General Hospital, Hillerød, Denmark
Chapter 4.5.2
Sidney Benjamin  Senior Lecturer, University of Manchester, UK
Chapter 5.2.6
Thomas P . Berney  Consultant Developmental Psychiatrist Honorary

Thomas P . Berney  Consultant Developmental Psychiatrist Honorary 
Research Associate, University of Newcastle upon Tyne
Chapter 10.6
Jose M. Bertolote  Chief, Mental Disorders Control Unit, World 
Health Organization, Geneva; Associate Professor, Department of Psychogeriatrics, University of Lausanne, Switzerland
Chapter 7.4
Zubin Bhagwagar  CT Mental Health Center, Y ale University, New Haven 
CT, USA 
Chapter 6.2.3
Mary Beth Connolly Gibbons  Assistant Professor of Psychology in 
Psychiatry Department of Psychiatry, University of Pennsylvania, Pennsylvania, USA 
Chapter 6.1.2

xxii
Dinesh Bhugra Professor of Mental Health and Cultural Diversity, King’s 
College London, Institute of Psychiatry, London, UK
Chapter 7.10.3
Michel Billiard Professor of Neurology, School of Medicine, Guide Chauliac 
Hospital, Montpellier, France
Chapter 4.14.3
Max Birchwood  Director, Early Intervention Service, Northern 
Birmingham Mental Health Trust, and University of Birmingham, UK
Chapter 6.3.2.4
Boris Birmaher  UPMC Western Psychiatric Institute, Pittsburgh, USA 
Chapter 9.2.7
Stella Bitran , Center for Anxiety and Related Disorders, Boston University, 
Beacon, MA 
Alan H. Bittles Centre for Comparative Genomics, Murdoch University, 
Perth, Australia
Chapter 8.1
Dora Black  Honorary Consultant, Child and Adolescent Psychiatry, 
Traumatic Stress Clinic, London; Honorary Lecturer, University of London, UK
Chapters 9.3.2 and 9.3.7
Michelle A. Blackmore , Doctoral Student of Clinical Psychology

Michelle A. Blackmore , Doctoral Student of Clinical Psychology 
Adult Anxiety Clinic at T emple University, Philadelphia, Pennsylvania, USA 
Chapter 4.7.2
Carlos Blanco New Y ork State Psychiatric Institute, New Y ork, 
Chapter 6.3.3
Sidney Bloch  Professor of Psychiatry, University of Melbourne; 
Senior Psychiatrist, St Vincent’s Hospital, Melbourne, Australia
Chapters 1.5 and 6.3.8
William V . Bobo Assistant Professor of Psychiatry, Vanderbilt University 
School of Medicine Nashville, T ennessee (USA) 
Chapter 6.2.5
Bernhard Bogerts  Department of Psychiatry, University of Magdeburg, 
Germany
Chapter 2.3.5
Jeff Bostic  School of Psychiatry, Harvard Medical School, Cambridge MA, 
USA
Chapter 9.1.3
Nick Bouras  Professor, Institute of Psychiatry - King’s College London
MHiLD - Y ork Clinic, London, UK
Chapter 10.9
Christopher R. Bowie Department of Psychiatry, Mount Sinai School of

Christopher R. Bowie Department of Psychiatry, Mount Sinai School of 
Medicine, New Y ork, USA 
Chapter 4.3.3
Colin Bradbury Department of Psychological Medicine, Institute of 
Psychiatry, De Crespigny Park, London, UK 
Chapter 4.2.4
Brian P . Brennan Instructor in Psychiatry, Harvard Medical School and 
Associate Director for Translational Neuroscience Research, Biological Psychiatry Laboratory, McLean Hospital, Belmont, MA 
Chapter 6.2.6David Brent Dept of Psychiatry, University of Pittsburgh Medical School, 
Pittsburgh PA, USA 
Chris R. Brewin  Research Dept of Clinical, Educational & Health 
Psychology, University College London, UK
Chapter 4.6.3
Elaine Brohan Institute of Psychiatry, David Goldberg Centre, 
De Crespigny Park, London, UK 
Chapter 1.2
Ian Brockington  Professor of Psychiatry, University of Birmingham, UK
Chapter 5.4

George W. Brown  Professor of Sociology, Academic Department of 
Psychiatry, St Thomas’s Hospital, London, UK
Chapter 2.6.1
Arne Brun  Professor of Neuropathology. Department of Pathology, 
Lund University Hospital, Lund, Sweden 
Chapter 4.1.3
Richard A. Bryant  School of Psychology, University of New South Wales, 
Sydney NSW, Australia 
Chapter 4.6.1
E.T. Bullmore  Institute of Psychiatry, King’s College London, UK
Chapters 2.3.7 and 2.3.8
T om Burns Professor of social psychiatry, Dept of Psychiatry, University of 
Oxford, Warneford Hospital, Oxford, UK 
Chapter 7.5
Jos´e Luis Carrasco  Professor of Psychiatry, Hospital Fundacion Jimenez 
Diaz, Universidad Autonoma, Madrid, Spain
Chapter 4.12.3
D.J. Castle  University of Western Australia, Fremantle, Australia
Chapter 4.3.6.1

Jonathan Chick  Consultant Psychiatrist, NHS Lothian, and Senior Lecturer, 
Department of Psychiatry, University of Edinburgh
Chapter 4.2.2.4
Daniel Chisholm  Department of Health System Financing, Health 
Systems and Services, World Health Organization, Geneva, Switzerland
Chapter 7.7
David Christmas  Dept of Psychiatry, University of Dundee, Dundee, UK 
Chapter 6.2.10.4
David M. Clarke  Consultant Psychiatrist, Lea Castle Centre, Kidderminster 
DY10 3PP
Chapters 6.3.3.1 and 10.4
L. Clark  Dept of Experimental Psychology, University of Cambridge, 
Cambridge, UK 
Chapter 2.5.5
Judy Clegg  Lecturer, Speech and language therapist, HPC, RCSLT 
Department of Human Communication Sciences University of Shefﬁ  eld, UK
Chapter 9.2.11
C. Robert Cloninger  Dept of Psychiatry, Washington University School of 
Medicine, St Louis MO, USA

Medicine, St Louis MO, USA 
Chapter 1.8.2contributors list

xxiii
John Collinge  Head of the Department of Neurodegenerative Disease at the 
Institute of Neurology, University College London and the Director of 
the UK Medical Research Council’s Prion Unit, London, UK
Chapter 4.1.4
Henry O’Connell Consultant Psychiatrist, Co. Tipperary, Ireland
Chapter 8.5.2
Melissa A. Culhane  Harvard Program in Refugee Trauma, Department of 
Psychiatry, Massachusetts General Hospital, Cambridge, USA 
Chapter 7.10.1
John E. Cooper Emeritus Professor of Psychiatry, University of 
Nottingham, UK 
Chapter 1.8.1
Sally-Ann Cooper  Professor of Learning Disabilities, Division of 
Community Based Sciences, Faculty of Medicine, University of Glasgow 
Chapter 10.2
Zafra Cooper Principal Research Psychologist, Oxford University 
Department of Psychiatry, Warneford Hospital, Oxford, UK 
Chapters 4.10.2 and 6.3.2.2
E. Jane Costello  Department of Psychiatry and Behavioral Sciences, 
Duke University Medical Center, Brightleaf Square, Durham NC 

Elizabeth Coulthard  Institute of Neurology, University College 
London, UK 
Chapter 2.5.2
F.-R. Cousin  Psychiatrist, Centre Hospitalier Saint-Anne, Paris, France
Chapter 4.3.10
Philip J. Cowen  Professor of Psychopharmacology, Department of 
Psychiatry, University of Oxford
Chapter 6.2.10.2
T om K.J. Craig Professor of Social Psychiatry, King’s College London, 
Institute of Psychiatry, London UK
Chapters 7.10.2 and 7.10.3
Paul Crits-Christoph  Professor of Psychology in Psychiatry Director, 
Center for Psychotherapy Research Department of Psychiatry, University of Pennsylvania. Pennsylvania, USA
Michael Crowe  Consultant Psychiatrist, South London and 
Maudsley NHS Trust; Honorary Senior Lecturer, Institute of Psychiatry, King’s College London, UK
Chapter 6.3.7

D.G. Cunningham Owens  Reader in Psychiatry, Department of Psychiatry, 
University of Edinburgh, UK
Chapter 4.3.8
Dianne Currier  Division of Molectular Imaging & Neuropathology, 
Department of Psychiatry, Columbia University 
Chapter 4.15.3
Robert Dantzer  Integrative Immunology and Behavior Program, University 
of Illinois at Urbana-Champaign, Edward R. Madigan Laboratory, West Gregory Drive, Urbana, IL, USA 
Chapter 2.3.10
Rajan Darjee Division of Psychiatry, University of Edinburgh, Edinburgh, UK 
Chapter 11.3.1Anthony S. David  Professor of Cognitive Neuropsychiatry, Institute of 
Psychiatry, King’s College London, UK
Chapters 4.3.4 and 4.9
Kate Davidson  Senior Research Psychologist, Department 
of Psychological Medicine, University of Glasgow, UK
Chapter 4.12.7

Martin Davies  Dept of Experimental Psychology, University of Oxford, 
Oxford, UK 
Chapter 2.1
Giovanni de Girolamo  Health Care Research Agency, Emilia-Romagna 
Region, Bologna, Italy
Chapters 4.12.2 and 4.12.4
Shoumitro Deb Clinical Professor of Neuropsychiatry & Intellectual 
Disability, Division of Neuroscience, University of Birmingham, UK
Chapter 10.4
R.J. Dolan Institute of Neurology, University College London, UK 
Chapter 2.5.4
Anton Došen  Emeritus Professor of Psychiatric Aspects of Intellectual 
Disability at the Radboud University, Nijmegen, The Netherlands
Chapter 10.5.2
D. Colin Drummond Professor of Addiction Psychiatry, Section of Alcohol 
Research, National Addiction Centre, Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King’s College London

Chapter 4.2.2.5
Emma Dunn  School of Medicine, Cardiff University, Cardiff, UK 
Chapter 11.17
Graham Dunn Professor of Biomedical Statistics, Health Methodology 
Research Group, School of Community Based Medicine, University of Manchester
Chapter 2.2
Julie Dunsmore Honorary Clinical Associate, SciMHA Unit, University of 
Western Sydney, Australia 
Chapter 4.6.5
Anke Ehlers  Department of Psychiatry, University of Oxford, UK
Chapters 4.6.1 and 4.6.2
Timo Erkinjuntti Professor of Neurology, Head of the University 
Department of Neurological Sciences, University of Helsinki and Head Physician, Department of Neurology and Memory Research Unit, Helsinki University Central Hospital, Finland
Chapter 4.1.8
Brigette A. Erwin  Adult Anxiety Clinic of T emple University, Philadelphia, 
Pennsylvania, USA

Colin A. Espie  Professor of Clinical Psychology and Head of Department of 
Psychological Medicine, University of Glasgow, UK
Jonathan J. Evans Section of Psychological Medicine, University of Glasgow, 
Glasgow, UK 
Chapter 4.1.14
Christopher G. Fairburn  Wellcome Principal Research Fellow and 
Professor of Psychiatry, University of Oxford, UK
Chapters 4.10.2 and 6.3.2.2contributors list

xxiv
Peter Falkai  Professor of Medical Psychology, Rheinische 
Friedrich-Wilhelms-Universität, Bonn, Germany
Stephen V . Faraone  Director, Medical Genetics Research, Professor of 
Psychiatry and of Neuroscience & Physiology, Director, Child and Adolescent Psychiatry Research, SUNY Upstate Medical University, New York
Chapter 4.3.9
Michael Farrell  Senior Lecturer and Consultant Psychiatrist, National 
Addiction Centre, South London and Maudsley NHS Trust, London, UK
Chapter 4.2.3.4
David P . Farrington  Professor of Psychological Criminology, University of 
Cambridge, UK
Chapter 11.2
J. Paul Fedoroff  Director, Sexual Behaviors Clinic Royal Ottawa Mental 
Health Centre and Director of Forensic Research University of Ottawa Institute of Mental Health Research 
Chapter 4.11.3
Howard H. Feldman  Professor and Head, Division of Neurology, 
Department of Medicine, University of British Columbia, Vancouver, BC, Canada 
Chapter 8.5.1.1

Melanie J.V . Fennell  Consultant Clinical Psychologist; Director, Oxford 
Diploma in Cognitive Therapy, University of Oxford Department of Psychiatry, Warneford Hospital, Oxford, UK
Chapter 6.3.2.3
Max Fink  Emeritus Professor of Psychiatry and Neurology, State University 
of New Y ork at Stony Brook; Professor of Psychiatry, Albert Einstein College of Medicine; Attending Psychiatrist, Long Island Jewish Medical Center, New Y ork, USA
Chapter 6.2.10.1
Michael B. First  Columbia University, New Y ork, USA 
Chapter 1.9
Per Fink  Director, Research Unit for Functional Disorders, Aarhus 
University Hospital, Risskov, Denmark
Chapter 5.2.3
Philip A. Fisher  Research Scientist, Oregon Social Learning Center, 
Eugene, Oregon, USA
Chapter 9.5.4
Martine F. Flament  Chargée de Récherche INSERM, CNRS UMR 7593, 
Paris, France

Chapter 9.2.8
Simon Fleminger Consultant Neuropsychiatries, Lishman Brain Injury 
Unit, Maudsley Hospital, London, UK
Chapters 4.1.10 and 4.1.13
Jonathan Flint Wellcome Trust Centre for Human Genetics Roosevelt 
Drive, Oxford
Chapter 2.4.2
Susan Folstein Professor of Psychiatry and Behavioral Sciences, 
Johns Hopkins School of Medicine, Baltimore, USA
Chapter 4.1.7
Peter Fonagy  Freud Memorial Professor of Psychoanalysis, University 
College London; Director of Research, Anna Freud Centre, London, UK; Director, Child and Family Center and Clinical Protocols and 
Outcomes Center, Menninger Clinic, T opeka, Kansas, USA
Chapters 4.12.6, 6.3.5 and 9.5.2
Gillian C. Forrest  Consultant Child and Adolescent Psychiatrist 
Chapter 9.5.8

Leah Fostick Department of Psychiatry, Chaim Sheba Medical Centre, 
T el Hashomer, Israel 
Chapter 4.8
W. Fraser  Division of Psychological Medicine, University of Wales College 
of Medicine, Cardiff, UK
Introduction to Section 10
Laura Fratiglioni Aging Research Centre, Karolinska Institute, 
Stockholm, Sweden 
Chapter 8.3
David M. Fresco  Adult Anxiety Clinic of T emple University, 
Philadelphia, Pennsylvania, USA
K.W.M. Fulford  Professor of Philosophy and Mental Health, 
University of Warwick; Honorary Consultant Psychiatrist, University of Oxford, UK
Chapter 1.5.2
Robert Fung , Specialist Registrar in Psychiatry, Shefﬁ  eld Care 
NHS Trust, UK 
Chapter 4.2.3.2
Pier Maria Furlan Director of Department of Mental Health San Luigi 
Gonzaga Hospital - University of T orino, Italy 
Chapter 5.5

Glen O. Gabbard  Bessie Walker Callaway Distinguished Professor of 
Psychoanalysis and Education in the Kansas School of Psychiatry, Menninger Clinic, T opeka; Clinical Professor of Psychiatry of Kansas School of Medicine, Wichita, Kansas, USA
Chapter 3.3
Jean Garrabé  Honorary President of L’Evolution psychiatrique, Paris
M. Elena Garralda  Professor of Child and Adolescent Psychiatry, Imperial 
College of Medicine, London, UK
Chapter 9.3.4
Ann Gath  Formerly of University College London, UK
Chapter 10.8
John R. Geddes Professor of Epidemiological Psychiatry, Department of 
Psychiatry, University of Oxford, Warneford Hospital, Oxford
Chapters 1.10 and 4.5.1
David Gill  Research Fellow, Department of Psychiatry, University of 
Oxford, UK
Chapters 5.2.9

Oxford, UK
Kathryn J. Gill  MUHB Addictions Unit, McGill University, Montreal QC, 
Canada
Chapter 4.2.2.1
Julia Gledhill  Clinical Research Fellow, Imperial College of Medicine, 
London, UK
David Goldberg  Director of Research and Development, Institute of 
Chapter 7.8contributors list

xxv
T erry E. Goldberg The Zucker Hillside Hospital, Glen Oaks NY, USA 
Chapter 2.5.3
Guy Goodwin Professor, University Department, Warneford Hospital, 
Oxford
Chapter 4.5.6
Kevin Gournay Emeritus Professor, Institute of Psychiatry, King’s College 
London
Chapter 6.4.2
Simon G. Gowers Professor of Adolescent Psychiatry, University of 
Liverpool 
Chapter 9.5.9
Cynthia A. Graham , Oxford Doctoral Course in Clinical Psychology 
Warneford Hospital, Oxford and The Kinsey Institute for Research in Sex, Gender, & Reproduction 
Philip Graham  Emeritus Professor of Child Psychiatry, Institute of Child 
Health, London 
Chapter 9.5.3
P .M. Grasby  Senior Lecturer, MRC Cyclotron Unit, Hammersmith Hospital, 
London, UK
Chapter 2.3.6
Richard Green  Head, Gender Identity Clinic, and Visiting Professor of 
Psychiatry, Imperial College of Medicine at Charing Cross Hospital, London, UK; Emeritus Professor of Psychiatry, University of California, Los Angeles, California, USA

Chapters 4.11.4 and 9.2.12
Stephen Green  Clinical Professor of Psychiatry, Georgetown University 
School of Medicine, Washington, D.C. 
Chapter 1.5.1 
Michael Gunn  Professor of Law and Head of Department, Department 
of Academic Legal Studies, Nottingham Law School, Nottingham Trent University, UK
Chapter 11.1
Lars Gustafson  Professor of Geriatric Psychiatry, Lund University Hospital, 
Lund, Sweden
Francesca Guzzetta  Bologna, Italy 
Chapter 4.12.4
Jennifer Gutstein  Department of Child Psychiatry, College of Physicians 
and Surgeons, Columbia University, New Y ork, USA
Chapter 9.2.10
Sarah Harper  Oxford Institute for Aging, University of Oxford, 
Oxford, UK 
Chapter 8.2
Rex Haigh Project Lead, Community of Communities, Centre for Quality

Oxford, UK 
Rex Haigh Project Lead, Community of Communities, Centre for Quality 
Improvement, Royal College of Psychiatrists, London; Consultant Psychiatrist, Berkshire Healthcare NHS Foundation Trust 
Chapter 6.3.9
S.A. Hales  Psychiatry Fellow, Princess Margaret Hospital, University Health 
Network, T oronto, Canada
John N. Hall  Professor of Mental Health, School of Health and Social Care, 
Oxford Brookes University, Oxford, UK
Chapter 1.8.3W ayne Hall  Professor of Public Health Policy, University of Queensland, 
Herston, Australia
Chapter 4.2.3.7
Edwin Harari  Consultant Psychiatrist, St Vincent’s Hospital, Melbourne, 
Australia
Chapter 6.3.8
Sarah Harper  Oxford Institute for Aging, University of Oxford, Oxford, UK
James C. Harris Director Developmental Neuropsychiatry Clinic, Professor

Australia
James C. Harris Director Developmental Neuropsychiatry Clinic, Professor 
of Psychiatry and Behavioral Sciences, Pediatrics, and Mental Hygiene, The Johns Hopkins University School of Medicine
Chapter 9.2.1
Paul J. Harrison  Clinical Reader in Psychiatry, University of 
Oxford Department of Psychiatry, Warneford Hospital, Oxford, UK
Chapter 4.3.6.2
Allison G. Harvey  Department of Experimental Psychology, 
University of Oxford, UK
Philip D. Harvey Professor of Psychiatry and Behavioral Sciences, Emory 
University School of Medicine, Woodruff Memorial Building, Atlanta, GA, USA 
Keith Hawton  Director, Centre for Suicide Research, University 
Department of Psychiatry, Warneford Hospital, Oxford
Chapter 4.15.4
Richard G. Heimberg  Adult Anxiety Clinic of T emple University, 

Scott Henderson Emeritus Professor, The Australian National University, 
Canberra, Australia
Chapters 2.7 and 8.3
George R. Heninger  Professor, Department of Psychiatry, Y ale University 
School of Medicine, New Haven, Connecticut, USA
Leslie Hicks , University of Y ork, UK 
Chapter 9.5.6
A.J. Holland  Lecturer, Department of Psychiatry, University of Cambridge, UK
Chapter 10.1
Jimmie C. Holland Wayne E. Chapman Chair in Psychiatric Oncology, 
Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New Y ork, USA
Chapter 5.3.7
Sheila Hollins  Professor of Psychiatry of Learning Disability, Department 
of Psychiatry and Disability, St George’s Hospital Medical School, University of London, UK
Chapter 10.7
Jeremy Holmes  Consultant Psychiatrist/Psychotherapist,

Jeremy Holmes  Consultant Psychiatrist/Psychotherapist, 
North Devon District Hospital, Barnstaple; Senior Lecturer, University of Bristol, UK
Chapter 3.2
Suzanne Holroyd Professor, Director of Geriatric Psychiatry, Department 
of Psychiatry and Neurobehavioral Science, University of Virginia, Charlottesville V A
Chapter 8.5.6contributors list

xxvi
Geraldine Holt Honorary Senior Lecturer in Psychiatry at the Institute of 
Allan House  Professor of Liaison Psychiatry, University of Leeds, UK
Chapter 5.3.1
Daniel H. Hovelson The Harvard program in refugee trauma, 
Massachusetts general hospital, Dept of psychiatry. 
Jane Hubert  Senior Lecturer in Social Anthropology, Department of 
Psychiatry and Disability, St George’s Hospital Medical School, University of London, UK
Stephen Hucker University of T oronto, T oronto, Canada 
Chapter 11.8
T. A. Hughes Consultant Psychiatrist, St Mary’s Hospital, Leeds, UK 
Chapter 4.1.6 
Masud Husain Institute of Neurology & Institute of Cognitive 
Neuroscience, UCL, London and National Hospital for Neurology & Neurosurgery, London 
Frits J. Huyse Psychiatrist, Consultant integrated care, Department of 
General Internal Medicine, University Medical Centre Groningen (UMCG), Groningen, The Netherlands

Chapter 5.7
Matti Iivanainen  Professor, Department of Child Neurology, University of 
Helsinki, Finland
Chapter 10.5.3
Leslie Iversen  Visting Professor, Department of Pharmacology, University 
of Oxford, UK
Chapter 6.2.7
Richard Ives  National Children’s Bureau, London, UK
Chapter 4.2.3.6
Assen Jablensky  Professor of Psychiatry, University of Western Australia, 
Chapters 4.3.5 and 4.3.7
Robin Jacoby  Clinical Reader in the Psychiatry of Old Age, University of 
Oxford, UK
Chapters 8.4 and 8.5.7
Claudia Jacova  Assistant Professor, Division of Neurology, Department of 
Medicine, University of British Columbia, Vancouver, BC, Canada
David V . James Consultant Forensic Psychiatrist, North London Forensic 
Service and Fixated Threat Assessment Centre 
Chapter 11.6

Kay Redﬁ  eld Jamison  Professor of Psychiatry, Johns Hopkins School of 
Medicine, Baltimore, Maryland, USA
Chapter 1.1
John G.R. Jefferys  Department of Neurophysiology, Division of 
Neuroscience, University of Birmingham, UK
Chapter 2.3.9
Andrew Johns  Consultant Forensic Psychiatry and Honorary Senior 
Lecturer, Maudsley Hospital, London, UK
Chapter 11.3.2.E.C. Johnstone  Professor of Psychiatry and Head, Department of 
Psychiatry, University of Edinburgh, UK
David P .H. Jones  Senior Clinical Lecturer in Child Psychiatry, 
Park Hospital for Children, University of Oxford, UK
Chapter 9.3.3
Peter R. Joyce  Professor, Department of Psychological Medicine, 
Christchurch School of Medicine, Christchurch, New Zealand
Chapter 4.5.4
Elizabeth Juven-W etzler Department of Psychiatry, Chaim Sheba Medical

Elizabeth Juven-W etzler Department of Psychiatry, Chaim Sheba Medical 
Centre, T el Hashomer, Israel 
Horst Kachele Universita ¨tsklinik Psychosomatische Medizin and 
Psychotherapie Universita ¨tsklinik Ulm, Germany
Chapter 6.3.5
Adam Ian Kaplin Assistant Professor, Departments of Psychiatry and 
Neurology, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, MD
Markus Kaski  Director, Rinnekoti Research Foundation, Director and 
Chief Physician of Rinnekoti Foundation, Espoo, Finland
Chapter 10.3
Aliya Kassam Institute of Psychiatry, David Glodberg Centre,
Roger G. Kathol , Adjunct Professor of Internal Medicine and Psychiatry, 
University of Minnesota, President, Cartesian Solutions, Inc. Burnsville, MN, USA 
Paul E. Keck Jr.  Lindner Center of HOPE, Mason, and Department of

Paul E. Keck Jr.  Lindner Center of HOPE, Mason, and Department of 
Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, USA 
Chapter 4.13.1
John Kellett  St George’s Hospital Medical School, London, UK
Chapter 8.5.8
Keith W. Kelley Department of Animal Sciences, University of Illinois, 
Urbana-Champaign, USA 
David Kennard Chair of the UK Network of the International Society for 
the Psychological Treatments of the Schizophrenias and other psychoses (ISPS UK); former Head of Psychology Services, The Retreat, Y ork, UK
Ad.J.F.M. Kerkhof  Professor of Clinical Psychology, Vrije Universiteit, 
Amsterdam, The Netherlands
Otto F . Kernberg  Professor of Psychiatry, Cornell University Medical 
College, New Y ork; Training and Supervising Analyst, Columbia University Center for Psychoanalytic Training and Research, New Y ork, USA

Chapter 3.1
Falk Kiefer Professor of Addiction Research, Deputy Director, Department 
of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health CIMH, University of Heidelberg, Mannheim, Germany 
Chapter 4.2.2.3contributors list

xxvii
Arthur Kleinman  Presley Professor of Anthropology and Psychiatry, 
Harvard University; Chair, Department of Social Medicine, 
Harvard Medical School, Cambridge, Massachusetts, USA
Chapter 2.6.2
Ami Klin  Y ale University, New Haven, Connecticut, USA
Chapter 9.2.3
Kimberly Klipstein  Department of Psychiatry, Mount Sinai School of 
Chapter 4.6.4
Martin Knapp  Institute of Psychiatry, King’s College London; 
London School of Economics and Political Science, University of London, UK
Michael D. Kopelman Professor of Neuropsychiatry at King’s College 
London, Institute of Psychiatry, UK
Chapter 4.1.12
Malcolm Lader Emeritus Professor of Clinical Psychopharmacology, King’s 
College London, Institute of Psychiatry, Denmark Hill, London, UK
Chapter 6.2.2
Fergus D. Law  Honorary Senior Registrar and Clinical Lecturer, 
Psychopharmacology Unit, University of Bristol, UK
Chapters 4.2.1 and 6.2.8

Brian Lawlor  Conolly Norman Professor of Old Age Psychiatry, St. James’s 
Hospital & Trinity College, Dublin, Ireland 
Dusica Lecic-T osevski Professor of Psychiatry, Institute of Mental Health, 
School of Medicine, University of Belgrade, Belgrade, Serbia
Julian Leff Emeritus Professor, Department of Psychological Medicine, 
Institute of Psychiatry, King’s College London, UK
Chapter 1.3.2
R.J. Levin  Department of Biomedical Science, University of Shefﬁ  eld, UK
Chapter 4.11.1
Rhohel Lenroot Child Psychiatry Branch, NIMH, Bethesda MD, USA 
Chapter 9.1.4
Peter F . Liddle  Professor of Psychiatry, University of British Columbia, 
Vancouver, British Columbia, Canada
Chapter 4.3.2
Felice Lieh Mak  Emeritus Professor, Department of Psychiatry, University 
of Hong Kong, Hong Kong
Chapter 5.2.10

James Lindesay  Professor of Psychiatry for the Elderly, University of 
Leicester, UK
Chapters 8.5.1 and 8.5.5
Jouko K. Lonnqvist  Professor, National Public Health Institute, 
Chapter 4.15.1
Juan J. López-Ibor Jr.  Chairman, Department of Psychiatry, San Carlos 
University Hospital, Complutense University, Madrid, Spain
Chapters 1.6 and 4.12.1
Ma Inés López-Ibor Madrid, Spain 
Chapter 4.2.3.8Simon Lovestone Professor of Old Age Psychiatry, NIHR Biomedical 
Research Centre for Mental Health, MRC Centre for Neurodegeneration 
Research, Departments of Psychological Medicine and Neuroscience, King’s College London, Institute of Psychiatry, London, UK
Chapter 4.1.2
Leanne Magee  T emple University, Philadelphia, Pennsylvania, USA 
Andrew McCulloch  The Mental Health Foundation, London, UK

Andrew McCulloch  The Mental Health Foundation, London, UK 
Chapter 7.1
Jane McCarthy  Division of Mental Health, St George’s Hospital, 
London, UK 
Susan L. McElroy  Lindner Center of HOPE, Mason, and Department of 
Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA 
Peter McGufﬁ  n Director and Professor of Psychiatric Genetics, Institute of 
Chapter 2.4.1
I.G. McKeith Clinical Director, Institute for Ageing and Health, Newcastle 
University, Newcastle Upon Tyne, UK
Chapter 4.1.5
Kwame McKenzie Centre for Addictions and Mental Health, T oronto, 
Canada; University of T oronto, Canada; University of Central Lancashire, UK
Chapter 7.3
Declan McLoughlin Institute of Psychiatry, King’s College London, UK 
Chapter 6.2.10.3
Mark W. Mahowald  Director, Minnesota Regional Sleep Disorders Center,

Mark W. Mahowald  Director, Minnesota Regional Sleep Disorders Center, 
Hennepin County Medical Center; Professor of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota, USA
Chapter 4.14.4
Mario Maj  Institute of Psychiatry, University of Naples, Italy
Chapter 4.1.9
Ulrik Fredrik Malt  Professor of Psychiatry (Psychosomatic Medicine), 
National Hospital, University of Oslo, Norway
Chapter 5.3.8
J. John Mann Vice Chair for Research Scientiﬁ  c Director, Kreitchman PET 
Center, Columbia University and Chief, Division of Molecular Imaging & Neuropathology, New Y ork State Psychiatric Institute, USA
Karl F. Mann Professor and Chair in Addiction Research, Deputy Director 
Central Institute of Mental Health (CIMH), University of Heidelberg, Mannheim, Germany
Chapter 4.2.2.3
Russell L. Margolis Professor of Psychiatry and Neurology Director,

Russell L. Margolis Professor of Psychiatry and Neurology Director, 
Johns Hopkins Schizophrenia Program Director, Laboratory of Genetic Neurobiology Division of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, USA 
John C. Markowitz  Associate Professor of Psychiatry, Weill Medical College 
of Cornell University; Director, Psychotherapy Clinic, Payne Whitney Clinic, New Y ork Presbyterian Hospital, New Y ork, USA
Chapter 6.3.3contributors list

xxviii
John Marsden  Lecturer, Institute of Psychiatry, King’s College London, UK
Jane Marshall  Senior Lecturer in the Addictions, National Addiction 
Centre, Institute of Psychiatry, King’s College London, UK
Chapters 4.1.11 and 4.2.2.2
Andrés Martin Professor of Child Psychiatry, Child Study Center Y ale 
University School of Medicine, New Haven, Connecticut, USA 
Keith Matthews Dept of Psychiatry, University of Dundee, Dundee, UK 
Barbara Maughan  MRC Child Psychiatry Unit, Institute of Psychiatry, 
King’s College London, UK
Chapter 9.3.1
Soraya Mayet  National Addiction Centre, Institute of Psychiatry, King’s 
College London, UK 
Chapter 4.2.3.1
Richard Mayou  Emeritus Professor of Psychiatry, University of Oxford, UK
Chapter 5.2.1
Nick Medford  Institute of Psychiatry, King’s College London, UK 
Chapter 4.9
David Meagher  Dept of Adult Psychiatry, Midwestern Regional Hospital, 
Limerick, Ireland 
Chapter 4.1.1

Thomas W. Meeks  Division of Geriatric Psychiatry, University of California 
San Diego, La Jolla CA, USA 
Chapter 8.5.3
Pamela S. Melding  Honorary Senior Lecturer, Department of Psychological 
Medicine, University of Auckland, New Zealand and Consultant in Psychiatry of Old Age, Mental Health Serviced, North Shore Hospital, Waitemata District Health Board, Takapuna, North Shore City, Auckland, New Zealand 
Chapter 8.7 
Herbert Y . Meltzer  Bixler/May/Johnaon Professor of Psychiatry, Professor 
of Pharmacoloqy Vanderbilt University School of Medicine, Nashville, T ennessee, USA
Julien Mendlewicz  Department of Psychiatry, University Clinics of Brussels, 
Erasme Hospital, Brussels, Belgium
Chapter 4.5.5
Andreas Meyer-Lindenberg  Dept of Psychiatry, Central Institute of Mental

Andreas Meyer-Lindenberg  Dept of Psychiatry, Central Institute of Mental 
Health, Mannheim, Germany 
Gillian C. Mezey  Consultant and Senior Lecturer in Forensic Psychiatry, 
Traumatic Stress Service, St George’s Hospital Medical School, London, UK
Chapters 11.12 and 11.13
R.H.S. Mindham  Emeritus Professor of Psychiatry, University of Leeds, UK
Chapter 4.1.6
Andrew Mogg Institute of Psychiatry, King’s College London, UK 
Richard F. Mollica  Director, Harvard Program in Refugee Trauma; 
Associate Professor of Psychiatry, Harvard Medical School and Harvard School of Public Health, Cambridge, Massachusetts, USA
Chapter 7.10.1Emanuel Moran  Consultant Psychiatrist, Grovelands Priory Hospital, 
London, UK
Chapter 4.13.2
Stella Morris  Dept of Psychological Medicine, Hull Royal Inﬁ  rmary, Hull, UK 
Matt Muijen  WHO Regional Ofﬁ  ce for Europe, Copenhagen, Denmark 

London, UK
Paul E. Mullen  Professor of Forensic Psychiatry, Monash University; 
Clinical Director, Victorian Institute of Forensic Mental Health, Monash University, Melbourne, Australia
Chapters 11.10, 11.11 and 11.14
Alistair Munro  Emeritus Professor of Psychiatry, Dalhousie University, 
Halifax, Nova Scotia, Canada
Chapter 4.4
Rebecca Murphy  Research Psychologist, Oxford University Department of 
Psychiatry, Warneford Hospital, Oxford, UK 
Lynne Murray  Winnicott Research Unit, University of Reading, 
Reading, UK 
Chapter 9.3.6
R.M. Murray  Institute of Psychiatry, King’s College London, UK
Norbert Nedopil Professor of Forensic Psychiatry, Head of the Department

Norbert Nedopil Professor of Forensic Psychiatry, Head of the Department 
of Forensic Psychiatry at the Psychiatric Hospital of the University of Munich, Munich, Germany 
Chapter 11.3.3
Juan C. Negrete  Professor and Head, Addictions Psychiatry Program, 
University of T oronto, Canada
Gretchen N. Neigh Dept of Psychiatry and Behavioral Sciences, Emory 
University, Atlanta GA, USA 
Chapter 2.3.3
Charles B. Nemeroff  Reunette W. Harris Professor and Chairman, 
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
Giles Newton-Howes  Division of Neurosciences and Mental Health, 
Imperial College School of Medicine, London, UL 
Jeffrey Newcorm  Mount Sinai School of Medicine, New Y ork, USA
Russell Noyes Jr.  Department of Psychiatry, University of Iowa College of

Russell Noyes Jr.  Department of Psychiatry, University of Iowa College of 
Medicine, Iowa City, Iowa, USA
Chapter 5.2.5
David J. Nutt  Professor of Psychopharmacology and Head of Clinical 
Medicine, University of Bristol, UK
Margaret Oates  Senior Lecturer in Psychiatry, University of Nottingham, UK
James R.P . Ogloff  Victorian Institute of Forensic Mental Health, Thomas 
Embling Hospital, Fairﬁ  eld VIC, Australia 
Chapters 11.4 ,11.14, and 11.16 contributors list

xxix
John O’Grady  Knowle Hospital, Fareham, UK 
Chapter 11.15
Catherine Oppenheimer  Consultant Psychiatrist, Warneford Hospital, 
Oxford, UK
Chapter 8.5.8 and 8.6
Luca Ostacoli  Liaison Psychiatry and Psychosomatic Unit, Department of 
Mental Health, San Luigi Gonzaga Hospital - University of T orino, Italy 
Pierre Oswald  Dept of Psychiatry, ULB Erasme, Brussels, Belgium 
Barton W. Palmer Veterans Affairs Medical Center, University of California, 
San Diego CA, USA 
Gordon Parker Professor, University of New South Wales; and Executive 
Director, Black Dog Institute, Australia
Chapter 4.5.3
E.S. Paykel  Emeritus Professor of Psychiatry, Department of Psychiatry, 
University of Cambridge, UK
Chapter 4.5.8
John B. Pearce  Emeritus Professor of Child and Adolescent Psychiatry, 
University of Nottingham, UK
Chapters 9.4 and 9.5.1
†R.C.A. Pearson  Department of Biomedical Science, University of 
Shefﬁ  eld, UK
Chapter 2.3.1

Keith J. Petrie  Associate Professor, School of Medicine,University of 
Auckland, New Zealand
Chapter 5.6
Cynthia R. Pfeffer  Weill Medical College of Cornell University, 
New Y ork Presbyterian Hospital-Westchester Division, White Plains, New Y ork, USA
Katharine A. Phillips Professor of Psychiatry and Human Behavior, The 
Warren Alpert Medical School of Brown University; Director, Body Dysmorphic Disorder Program, Butler Hospital, Providence, USA
Chapter 5.2.8
Pierre Pichot  Académie Nationale de Médecine, Paris, France
Chapter 1.4
Harold Alan Pincus Columbia University, New Y ork, USA 
V anessa Pinfold  ‘Rethink’ , London, UK 
Chapter 7.9
Daniel S. Pine  Division of Intramural Research Programs, National 
Institutes of Health, Bethesda, USA 
Chapter 9.2.6

Malcolm Pines  Founding Member, Institute of Group Analysis, 
London, UK
Chapter 6.3.6
Harrison G. Pope Jr.  Professor of Psychiatry, Harvard Medical School, 
Boston; Chief, Biological Psychiatry Laboratory, McClean Hospital, Belmont, Massachusetts, USA
Chapter 6.2.6Robert M. Post  Chief, Biological Psychiatry Branch, National Institute of 
Mental Health, Bethesda, Maryland, USA
Chapter 6.2.4
Graham E. Powell  Psychology Services, Powell Campbell Edelmann, 
London, UK
Chapter 1.8.3
Herschel Prins  Professor, Midlands Centre for Criminology and Criminal 
Justice, University of Loughborough, UK
Chapter 11.9
Paul Ramchandani  Dept of Psychiatry, University of Oxford, 
Warneford Hospital, Oxford, UK 
Shulamit Ramon  Professor of Interprofessional Health and Social Studies,

Shulamit Ramon  Professor of Interprofessional Health and Social Studies, 
Anglia Polytechnic University, Cambridge, UK
Chapter 6.4.3
Beverley Raphael University of Western Sydney Medical School, 
James Reich Clinical Professor of Psychiatry, University of California, 
San Francisco Medical School and Adjunct Associate Professor of Psychiatry, Stanford School of Medicine
Chapter 4.12.2
Helmut Remschmidt  Director, Department of Child and Adolescent 
Psychiatry, Philipps Universität, Marburg, Germany
Chapter 9.2.2
Philippe Robaey  Institute of Mental Health Research, Royal Ottawa 
Hospital, Ottawa, Canada 
Ian Robbins  Consultant Clinical Psychologist, St George’s Hospital, 
London, UK
Chapter 11.13
T.W. Robbins Section of Forensic Psychiatry, St George’s Hospital Medical 
School, London, UK 

London, UK
G.M. Rodin  Professor of Psychiatry, University of T oronto, 
Maria A. Ron  Professor of Neuropsychiatry, Institute of Neurology, 
University College London, UK
Chapter 5.3.2
Robin Room Professor, School of Population Health, University of 
Melbourne; and Director, AER Centre for Alcohol Policy Research, Turning Point Alcohol and Drug Centre, Fitzroy, Victoria, Australia
Chapter 4.2.2.6
W. Rössler  Professor of Clinical Psychiatry and Psychology, University of 
Zürich, Switzerland
Chapter 6.4.1
James R. Rundell Department of Psychiatry and Psychology, Mayo Clinic 
Professor of Psychiatry, Mayo Clinic College of Medicine
Chapter 5.3.4
Gerald Russell  Emeritus Professor of Psychiatry, Director of the Eating 
Disorders Unit, Hayes Grove Priory Hospital, Hayes, Kent, UK
Chapter 4.10.1contributors list

xxx
B.J. Sahakian Dept of Psychiatry, University of Cambridge, 
Diana Sanders Chartered Counselling Psychologist, working in 
Psychological Medicine in Oxford, UK
Chapter 6.3.1
Paramala J. Santosh Great Ormond Street Hospital for Sick Children, 
London, UK 
Chapter 9.5.5
Benedetto Saraceno  Director of Department of Mental Health and 
Substance Abuse, World Health Organization WHO 
Chapter 1.3.1
Gauri N. Savla,  Veterans Affairs Medical Center, University of California, 
Carlos H. Schenck  Staff Psychiatrist, Minnesota Regional Sleep 
Disorders Center, Hennepin County Medical Center; Associate Professor of Psychiatry, University of Minnesota Medical School, Minneapolis, Minnesota, USA
John Schlapobersky  Consultant Psychotherapist, Trumatic Stress Clinic 
Middlesex/University College Hospital, formerly also of The Medical Foundation for the Care of Victims of T orture London, UK

Fabrizio Schiffano , Chair in Clinical Pharmacology and Therapeutics 
Associate Dean, Postgraduate Medical School, Hon Consultant Psychiatrist Addictions, University of Hertfordshire, School of Pharmacy, College Lane Campus, Hatﬁ  eld, UK 
Chapter 4.2.3.5
Gerd Schulte-Körne Director of the Department of Child and Adolescent 
Psychiatry, Psychosomatics and Psychotherapy, University of Munich, Pettenkoferstr, München/Germany 
J. Scott Professor of Psychological Medicine, University of Newcastle & 
Honorary Professor, Psychological Treatments Research, Institute of Psychiatry, London and University Department of Psychiatry, Leazes Wing, Royal Victoria Inﬁ  rmary, Newcastle upon Tyne, England
Stephen Scott Professor of Child Health & Behaviour, King’s College

Stephen Scott Professor of Child Health & Behaviour, King’s College 
London, Institute of Psychiatry, and Director of Research National Academy for Parenting Practitioners, London, UK
Chapters 9.1.1 and 9.2.5
Nicholas Seivewright  Consultant Psychiatrist in Substance Misuse, 
Community Health Shefﬁ  eld NHS Trust, Shefﬁ  eld, UK
David Shaffer  Department of Child Psychiatry, College of Physicians and 
Surgeons, Columbia University, New Y ork, USA
Trevor Sharp  Dept of Pharmacology, University of Oxford, Oxford, UK
Chapter 2.3.4
Michael Sharpe Professor of Psychological Medicine & Symptoms Research, 
Chapters 5.1 and 5.2.7Jennifer Shaw  Centre for Suicide Prevention, The School of Medicine, 
University of Manchester, UK 
Chapter 11.5
Mauricio Sierra  Institute of Psychiatry, King’s College London, UK 
Gregory Simon  Investigator, Center for Health Studies, Group Health

Gregory Simon  Investigator, Center for Health Studies, Group Health 
Cooperative, Seattle, Washington, USA
Chapter 5.2.2
Andrew Sims  Professor of Psychiatry, University of Leeds, UK
Chapter 1.7
Ian Sinclair  Professor of Social Work, University of Y ork, UK
Mike Slade  Health Service and Population Research Department 
and Institute of Psychiatry, King’s College London, UK 
Chapter 7.2
Elita Smiley Consultant Psychiatrist and Clinical Senior Lecturer, 
Division of Community Based Sciences, Faculty of Medicine, University of Glasgow, UK 
Wolfgang Söllner  Department of Psychosomatic Medicine and 
Psychotherapy General Hospital Nuremberg, Prof.Ernst-Nathan-Str. 1, Nürnberg, Germany 
Daniel Souery  Department of Psychiatry, University Clinics of Brussels, 

Elizabeth Spencer  Senior Clinical Medical Ofﬁ  cer, Early Intervention 
Service, Northern Birmingham Mental Health Trust, Birmingham, UK
David A. Spiegel  Center for Anxiety and Related Disorders at Boston 
University, Boston, Massachusetts, USA
Costas Stefanis Honorary Professor of Psychiatry, University of Athens, 
Greece
Chapter 1.6
Alan Stein  Royal Free and University College Medical School, University 
College London, and Tavistock Clinic, London, UK
Jessica Stiles Department of Psychiatry and Behavioral Sciences, Memorial 
Sloan Kettering Cancer Center, New Y ork, USA 
William S. Stone Assistant Professor of Psychology, Director of

William S. Stone Assistant Professor of Psychology, Director of 
Neuropsychology Training and Clinical Services, Department of Psychiatry, Harvard Medical School, Massachusetts Mental Health Center Public Psychiatry, Division of the Beth Israel Deaconess Medical Center, Boston, USA
Gregory Stores  Emeritus Professor of Developmental Neuropsychiatry, 
Chapters 4.14.1 and 9.2.9contributors list

xxxi
Elizabeth A. Stormshak  Assistant Professor, University of Oregon, Eugene, 
Oregon, USA
James J. Strain  Professor/Director, Behavioral Medicine and Consultation 
Psychiatry, Mount Sinai School of Medicine, New Y ork, USA
John Strang National Addiction Centre, Institute of Psychiatry, King’s 
College London, UK
Chapters 4.2.3.1 and 4.2.4
J. Suckling Brain Mapping Unit, Department of Psychiatry, University of 
Cambridge, Addenbrookes Hospital, Cambridge, UK
Nicola Swinson  Centre for Sucide Prevention, The School of Medicine, 
Michele T ansella  Professor of Psychiatry and Chairman, Department 
of Medicine and Public Health, Section of Psychiatry, University of Verona, Italy
Chapters 7.2 and 7.6
Mary Target  Senior Lecturer in Psychoanalysis, Psychoanalysis Unit, 
University College London; Deputy Director of Research, Anna Freud Centre, London, UK
Chapter 9.5.2

Eric T aylor Head of Department, Child & Adolescent Psychiatry, King’s 
College London, Institute of Psychiatry 
Chapter 9.2.4
John-Paul T aylor  Academic Specialist Registrar, Institute for Ageing 
and Health Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK 
Chapter 4.1.13
Pamela J. T aylor  School of Medicine, Cardiff University, Cardiff, UK 
T atiana T aylor  Dept of Psychiatry, University of Oxford, Warneford 
Hospital, Oxford, UK 
Chapter 4.15. 4
Mary T easdale  ‘Rethink’ , London, UK 
Anita Thapar Department of Psychological Medicine, School of Medicine, 
Cardiff University, UK
June Thoburn  Emeritus Professor of Social Work, University of East Anglia, 
Norwich, UK
Chapter 9.3.5

Sian Thomas  Chester Y oung People’s Centre, Shester, UK 
Lindsay Thomson Division of Psychiatry, University of Edinburgh, 
Edinburgh, UK 
Chapter 11.3.1
Anne E. Thompson Emeritus Professor Child and Adolescent Psychiatry, 
Chapter 9.4Graham Thornicroft  Professor of Community Psychiatry, Institute of 
Chapters 1.2, 7.2 and 7.6
Adolf T obeña Professor of Psychiatry, Director of the Dept. of Psychiatry 
and Forensic Medicine, Autonomous University of Barcelona, Bellaterra (Barcelona), Spain
Chapter 4.12.5
Bruce J. T onge Head Monash University School of Psychology Psychiatry & 
Psychological Medicine, Monash Medical Centre, Clayton, Victoria, Australia
Chapter 10.5.1
Brian T oone  Consultant, Maudsley Hospital; Honorary Senior Lecturer,

Brian T oone  Consultant, Maudsley Hospital; Honorary Senior Lecturer, 
Chapter 5.3.3
David Trickey  Leicester Royal Inﬁ  rmary, Leicestershire Partnership 
NHS Trust, UK
Paula Trzepacz  Eli Lilly & Co, USA 
W en-Shing Tseng Professor at Department of Psychiatry, University of 
Hawaii School of Medicine, USA 
Chapters 4.16 and 6.5
Ming T. Tsuang Behavioral Genomics Endowed Chair and University 
Professor, University of California; Distinguished Professor of Psychiatry and Director, Center for Behavioral Genomics, Department of Psychiatry, University of California, San Diego, CA, USA
André Tylee  Director, Royal College of General Practitioners Unit for 
Mental Health Education in Primary Care, Institute of Psychiatry, King’s College London, UK
Chapter 7.8

Amy M. Ursano  Department of Psychiatry, University of North Carolina at 
Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
Chapter 6.3.4
Robert J. Ursano  Professor and Chairman, Department of Psychiatry, 
Uniformed Services University of the Health Sciences, F. Edward Herbert School of Medicine, Bethesda, Maryland, USA
Jim van Os Professor of Psychiatric Epidemiology, Maastricht University, 
Maastricht, The Netherlands and Visiting Professor of Psychiatric Epidemiology Institute of Psychiatry, London, UK
Fred R. V olkmar  Y ale University, New Haven, Connecticut, USA
Jane Walker  Clinical Lecturer and Honorary Specialist Registrar in Liaison

Jane Walker  Clinical Lecturer and Honorary Specialist Registrar in Liaison 
Psychiatry, Psychological Medicine & Symptoms Research Group, School of Molecular & Clinical Medicine, University of Edinburgh, UK 
Chapter 5.1
Diane W aller Professor of Art Psychotherapy, Goldsmiths, 
University of London 
Chapter 6.4.4contributors list

xxxii
Paul Walters  MRC Fellow & Specialist Psychiatrist , Programme Leader MSc 
in Mental Health Services Research, Section of Primary Care Mental Health, Health Service and Population Research Department, David Goldberg Centre, Institute of Psychiatry, London, UK 
John W einmann Professor of Psychology as applied to Medicine, 
Myrna M. W eissman  Professor of Epidemiology in Psychiatry, 
College of Physicians and Surgeons of Columbia University; Chief, Division of Clinical and Genetic Epidemiology, New Y ork State Psychiatric Institute, New Y ork, USA
Sarah W elch Gloucestershire Partnership NHS Foundation Trust, UK
Ursula W erneke Consultant Psychiatrist, Norrkoping, Sweden 
Chapter 6.2.9
Simon W essely  Professor of Epidemiological and Liaison Psychiatry, 
Chapter 5.2.7

Kay Wheat  Senior Lecturer in Law, Department of Academic Legal Studies, 
Nottingham Law School, Nottingham Trent University, UK
Adam R. Winstock Senior Staff Specialist, Drug Health Services, 
Conjoint Senior Lecturer, National Drug and Alcohol Research Centre, UNSW
Chapters 4.2.3.1 and 4.2.3.5Sally W ooding  Senior Research Fellow, SciMHA Unit, University of Western 
Sydney, Australia 
Matt Woolgar  Institute of Psychiatry, King’s College London, UK 
Chapter 2.5.1
Miranda Wolpert Director of Child and Adolescent Mental Health Services, 
Evidence Based Practice Unit, University College London and Anna Freud Centre, UK 
Chapter 9.5.7
Lawson Wulsin  Professor of Psychiatry and Family Medicine, 
University of Cincinnati, OH, USA 
Richard Jed Wyatt† National Institutes of Mental Health, Bethesda,

Richard Jed Wyatt† National Institutes of Mental Health, Bethesda, 
Maryland, USA
William Yule  Professor of Applied Child Psychology, Institute of Psychiatry, 
Karl Zilles Professor, Institute of Neuroscience and Biophysics, INB-3 
Research Centre, Jülich and C.&O. Vogt Institute of Brain Research, University Düsseldorf, Germany
Chapter 2.3.2
Joseph Zohar  Psychiatric Medical Center, Sheba Medical Center, T el 
Hashomer and Sackler School of Medicine, T el Aviv University, Israel
Chapter 4.8contributors list

SECTION 1
The Subject Matter 
 1.3 Psychiatry as a worldwide public 
health problem  10
K. W. M. Fulford 1.6 The psychiatrist as a manager  39
Juan J. López-Ibor Jr. and Costas Stefanis
 1.7 Descriptive phenomenology  47
62

62
94

1.1
The patient’s perspective
Kay Redﬁ  eld Jamison, Richard Jed Wyatt,† 
and Adam Ian Kaplin
It is difﬁ  cult to be a psychiatric patient, but a good doctor can make 
it less so. Confusion and fear can be overcome by knowledge and compassion, and resistance to treatment is often, although by no means always, amenable to change by intelligent persuasion. The devil, as the ﬁ  ery melancholic Byron knew, is in the details.
Patients, when ﬁ  rst given a psychiatric diagnosis, are commonly

Patients, when ﬁ  rst given a psychiatric diagnosis, are commonly 
both relieved and frightened—relieved because often they have been in pain and anxiety for a considerable period of time, and frightened because they do not know what the diagnosis means or what the treatment will entail. They do not know if they will return to the way they once were, whether the treatment they have been prescribed will or will not work, and, even if it does work, at what cost it will be to them in terms of their notions of themselves, potentially unpleasant side-effects, and the reactions of their family 
members, friends, colleagues, and employers. Perhaps most dis-
turbing, they do not know if their depression, psychosis, anxieties, or compulsions will return to become a permanent part of their lives. Caught in a state often characterized by personal anguish, social isolation and confusion, newly diagnosed patients ﬁ  nd them-

selves on a quest to regain a sense of mastery of themselves and their surroundings. One of the main goals of therapies of all types is to empower the patient and give them some control back over their world.
The speciﬁ  cs of what the doctor says, and the manner in which 
he or she says it, are critically important. Most patients who com-plain about receiving poor psychiatric care do so on several grounds: their doctors, they feel, spend too little time explaining the nature of their illnesses and treatment; they are reluctant to consult with or actively involve family members; they are patron-izing, and do not adequately listen to what the patient has to say; they do not encourage questions or sufﬁ  ciently address the con-
cerns of the patient; they do not discuss alternative treatments, the risks of treatment, and the risks of no treatment; and they do not thoroughly forewarn about side-effects of medications.
Most of these complaints are avoidable. Time, although difﬁ  cult

Most of these complaints are avoidable. Time, although difﬁ  cult 
to come by, is well spent early on in the course of treatment when confusion and hopelessness are greatest, non-adherence is highest, and the possibility of suicide substantially increased. Hope can be realistically extended to patients and family members, and its explicit extension is vital to those whose illnesses have robbed them not only of hope, but of belief in themselves and their futures. The hope provided needs to be tempered, however, by an explication of possible difﬁ  culties yet to be encountered: unpleasant side-
effects from medications, a rocky time course to meaningful recov-ery which will often consist of many discouraging cycles of feeling well, only to become ill again, and the probable personal, profes-sional, and ﬁ  nancial repercussions that come in the wake of having 
a psychiatric illness.
It is terrifying to lose one’s sanity or to be seized by a paralysing

It is terrifying to lose one’s sanity or to be seized by a paralysing 
depression. No medication alone can substitute for a good doctor’s clinical expertise and the kindness of a doctor who understands both the medical and psychological sides of mental illness. Nor can any medication alone substitute for a good doctor’s capacity to listen 
to the fears and despair of patients trying to come to terms with 
what has happened to them. A good doctor is a therapeutic optimist who is able to instill hope and conﬁ  dence to combat confusion 
and despair. Great doctors are able to provide the unwavering care to their patients that they would want a member of their own family to receive, blending empathy, and compassion with expertise.
Doctors need to be direct in answering questions, to acknowl-

edge the limits of their understanding, and to encourage specialist consultations when the clinical situation warrants it. They also need to create a therapeutic climate in which patients and their families feel free, when necessary, to express their concerns about treatment or to request a second opinion. Treatment non-adherence, one of the major causes of unnecessary suffering, relapse, hospital-ization, and suicide, must be addressed head-on. Y oung males, early in the course of their illness, are particularly likely to stop medication against medical advice, and the results can be lethal.
(1,2)
Unfortunately, doctors are notoriously variable in their ability to assess and predict adherence in their patients.
(3)
Asking directly and often about medication concerns and

(1,2)
(3)
Asking directly and often about medication concerns and 
side-effects, scheduling frequent follow-up visits after the initial diagnostic evaluation and treatment recommendation, and encour-aging adjunctive psychotherapy, or involvement in patient support groups, can make a crucial difference in whether or not a patient takes medication in a way that is most effective. Aggressive treatment of unpleasant or intolerable side-effects, minimizing the dosage and number of doses, and providing ongoing, frequently repetitive 
†Deceased.

SECTION 1  the subject matter of and approach to psychiatry 4
education about the illness and its treatment are likewise essential, 
if common-sense, ways to avert or minimize non-adherence.
Education is, of course, integral to the good treatment of any 
illness, but this is especially true when the illnesses are chronic. The term ‘doctor’ derives originally from the Latin word for teacher, and it is in their roles as teachers that doctors provide patients with the knowledge and understanding to combat the confusion and unpredictability that surrounds mental illness. Patients and their family members should be encouraged to write down any ques-
tions they may have, as many individuals are intimidated once they 
ﬁ nd themselves in a doctor’s ofﬁ  ce. Any information that is given 
orally to patients should be repeated as often as necessary (due to the cognitive difﬁ  culties experienced by many psychiatric patients,

orally to patients should be repeated as often as necessary (due to the cognitive difﬁ  culties experienced by many psychiatric patients, 
especially when acutely ill or recovering from an acute episode) and, whenever feasible, provided in written form as well. Additional information is available to patients and family members in books and pamphlets obtainable from libraries, bookstores, and patient support groups, as well as from audiotapes, videotapes, and the Internet.
(2,4) Visual aids, such as charts portraying the natural 
course of the treated and untreated illness, or the causes and results of sleep deprivation and medication cessation, are also helpful to many.
(5–7) Finally, providing the patients with self-report scales

(5–7) Finally, providing the patients with self-report scales 
to monitor their daily progress, such as mood charts in affective disorder, not only provides invaluable clinical data, but also teaches patients to better understand their own illness and its response to therapeutic interventions as well as exacerbating stressors. Patients, when they are well, often beneﬁ  t from a meeting with 
their family members and their doctor, which focuses upon drawing up contingency plans in case their illness should recur. These meetings also provide an opportunity to shore up the sup-port system the patient has by educating their caregivers about the nature, cause, manifestations, and treatment of their loved one’s mental illness. Such meetings may also include what is to be done in the event that hospitalization is required and the patient refuses voluntary admission, a discussion of early warning signs of impending psychotic or depressive episodes, methods for regular-

izing sleep and activity patterns, techniques to protect patients 
ﬁ nancially, and ways to manage suicidal behaviour should it occur. 
Suicide is the major cause of premature death in the severe psychi-atric illnesses,
(8,9) and its prevention is of ﬁ  rst concern. Those 
illnesses most likely to result in suicide (the mood disorders, comorbid alcohol and drug abuse, and schizophrenia) need to be treated early, aggressively, and often for an indeﬁ  nite period of 
time.
(2,10) The increasing evidence that treatment early in psychiatric 
illness may improve the long-term course needs to be considered in light of the reluctance of many patients to stay in treatment.
(10,11)
No one who has treated or suffered from mental illness would 
minimize the difﬁ  culties involved in successful treatment. Modern

(10,11)
minimize the difﬁ  culties involved in successful treatment. Modern 
medicine gives options that did not exist even 10 years ago, and there is every reason to expect that improvements in psychophar-macology, psychotherapy, and diagnostic techniques will continue to develop at a galloping pace. Still, the relationship between the 
patient and doctor will remain central to the treatment, as Morag 
Coate wrote 35 years ago in Beyond All Reason :
(12)
Because the doctors cared, and because one of them still believed 
in me when I believed in nothing, I have survived to tell the tale. It is not only the doctors who perform hazardous operations or give life-

saving drugs in obvious emergencies who hold the scales at times between life and death. T o sit quietly in a consulting room and talk to someone would not appear to the general public as a heroic or dramatic thing to do. In medicine there are many different ways of saving lives. This is one of them.
Further information
Non-Governmental Mental Health Websites: US
http://www.nami.org/
http://www.dbsalliance.org/site/PageServer?pagename =home
Governmental Mental Health Websites: US
http://www.nimh.nih.gov/
http://www.hhs.gov/samhsa/mentalhealth/
Non-Governmental Mental Health Websites: UK
http://www.mentalhealth.org.uk/
http://www.depressionalliance.org/index.html
http://www.dh.gov.uk/en/Healthcare/NationalServiceFrameworks/
Mentalhealth/index.html
http://www.mentalhealthcare.org.uk/
References

 1. Jamison, K.R., Gerner, R.H., and Goodwin, F.K. (1979). Patient and 
physician attitudes toward lithium: relationship to compliance. Archives of General Psychiatry ,36, 866–9.
 2. Goodwin, F.K. and Jamison, K.R. (2007). Manic-depressive illness 
(2nd edn.). Oxford University Press, New Y ork.
 3. Osterberg, L. and Blaschke, T. (2005). Adherence to medication. 
The New England Journal of Medicine ,353, 487–97.
 4. Wyatt, R.J. and Chew, R.H. (2005). Practical psychiatric practice. 
Forms and protocols for clinical use  (3rd edn). American Psychiatric 
Association, Washington, DC.
 5. Post, R.M., Rubinow, D.R., and Ballenger, J.C. (1986). Conditioning 
and sensitisation in the longitudinal course of affective illness. The British Journal of Psychiatry ,149, 191–201.

5. Post, R.M., Rubinow, D.R., and Ballenger, J.C. (1986). Conditioning 
 6. Wehr, T.A., Sack, D.A., and Rosenthal, N.E. (1987). Sleep reduction as 
a ﬁ nal common pathway in the genesis of mania. The American Journal 
of Psychiatry ,144, 201–4.
 7. Baldessarini, R.J., T ondo, L., and Hennen, J. (2003). Lithium treatment 
and suicide risk in major affective disorders: update and new ﬁ  ndings. 
The Journal of Clinical Psychiatry ,64(Suppl. 5), 44–52.
 8. Harris, E.C. and Barraclough, B. (1997). Suicide as an outcome for 
mental disorders. A meta-analysis. The British Journal of Psychiatry ,
170, 205–28.
 9. Institute of Medicine (IoM). (2002). Reducing suicide: a national 
imperative . National Academy Press, Washington, DC.
10. Wyatt, R.J. (1995). Early intervention for schizophrenia: can the course 
of the illness be altered? Biological Psychiatry ,38, 1–3.

11. Berger, G., Dell’Olio, M., Amminger, P ., et al. (2007). Neuroprotection 
in emerging psychotic disorders. Early Intervention in Psychiatry ,1,
114–27.
12. Coate, M. (1964). Beyond all reason . Constable, London.

1.2
Introduction
The starting point for this discussion is the idea of stigma. This 
term (plural stigmata) was originally used to refer to an indelible dot left on the skin after stinging with a sharp instrument, some-times used to identify vagabonds or slaves.
(1–4) In modern times 
stigma has come to mean ‘any attribute, trait or disorder that marks an individual as being unacceptably different from the ‘normal’ people with whom he or she routinely interacts, and that elicits some form of community sanction.’
(5–7)
Understanding stigma
There is now a voluminous literature on stigma.(5,8) (9–13,13–19)
The most complete model of the component processes of stigmati-zation has four key components:
(20)
 i) Labelling, in which personal characteristics, which are 
signalled or noticed as conveying an important difference.
 ii) Stereoty ping, which is the linkage of these differences to 
undesirable characteristics.
 iii) Separating, the categorical distinction between the main-

ii) Stereoty ping, which is the linkage of these differences to 
stream/normal group and the labelled group as in some respects fundamentally different.
 iv) Status loss and discrimination: devaluing, rejecting, and 
excluding the labelled group. Interestingly, more recently the authors of this model have added a revision to include the emotional reactions which may accompany each of these stages.
(21,22)
Shortcomings of work on stigma
Five key features have limited the usefulness of stigma theories. First, while these processes are undoubtedly complex, academic writings on stigma (which in the ﬁ  eld of mental health have almost 
entirely focused upon schizophrenia) have made relatively few connections with legislation concerning disability rights policy
(23)

(23)
or clinical practice. Second, most work on mental illness and stigma has been descriptive, overwhelmingly describing attitude surveys or the portrayal of mental illness by the media. Very little is known about effective interventions to reduce stigma. Third, 
there have been notably few direct contributions to this literature by service users.
(24) Fourth, there has been an underlying pessi-
mism that stigma is deeply historically rooted and difﬁ  cult to 
change. This has been one of the reasons for the reluctance to use the results of research in designing and implementing action plans. Fifth, stigma theories have de-emphasized cultural factors and paid little attention to the issues related to human rights and social structures.
Recently there have been early signs of a developing focus upon

Recently there have been early signs of a developing focus upon 
discrimination. This can be seen as the behavioural consequences of stigma, which act to the disadvantage of people who are stigma-tized.
(23,25–27)  The importance of discriminatory behaviour has 
been clear for many years in terms of the personal experiences of service users, in terms of devastating effects upon personal rela-tionships, parenting and childcare, education, training, work, and housing.
(28) Indeed, these voices have said that the rejecting behav-
iour of others may bring greater disadvantage than the primary condition itself.
Stigma can therefore be seen as an overarching term that 
contains three important elements: 
(29)
◆ problems of knowledge ignorance
◆ problems of attitudes prejudice
◆ problems of behaviour discrimination
Ignorance: the problem of knowledge

(29)
At a time when there is an unprecedented volume of information in the public domain, the level of accurate knowledge about mental illnesses (sometime called ‘mental health literacy’) is meagre.
(30)
In a population survey in England, for example, most people (55 per cent) believe that the statement ‘someone who cannot be held responsible for his or her own actions’ describes a person who is mentally ill.
(31) Most (63 per cent) thought that fewer than 
10 per cent of the population would experience a mental illness at some time in their lives.
There is evidence that deliberate interventions to improve public 
knowledge about depression can be successful, and can reduce the effects of stigmatization. At the national level, social marketing Public attitudes and the 
challenge of stigma

Graham Thornicroft, Elaine Brohan, and 
Aliya Kassam

6
campaigns have produced positive changes in public attitudes 
towards people with mental illness, as shown recently in New Zealand and Scotland.
(32,33)  In a campaign in Australia to increase 
knowledge about depression and its treatment, some states and territories received this intensive, co-ordinated programme, while others did not. In the former, people more often recognized the features of depression, were more likely to support help seeking for depression, or to accept treatment with counselling and medication.
(34)
Prejudice: the problem of negative attitudes

(34)
Although the term prejudice is used to refer to many social groups, which experience disadvantage, for example minority ethnic groups, it is employed rarely in relation to people with mental illness. The reactions of a host majority to act with prejudice in rejecting a minority group usually involve not just negative thoughts but also emotion such as anxiety, anger, resentment, hostility, distaste, or disgust. In fact prejudice may more strongly predict discrimination than do stereotypes. Interestingly, there is almost nothing published about emotional reactions to people with mental illness apart from that which describes a fear of violence.
(35)
Discrimination: the problem of rejecting and 
avoidant behaviour
Surveys of attitude and social distance (unwillingness to have social

(35)
Surveys of attitude and social distance (unwillingness to have social 
contact) usually ask either students or members of the general public what they would do in imaginary situations or what they think ‘most people’ who do, for example, when faced with a neigh-bour or work colleague with mental illness. Important lessons have ﬂ  owed from these ﬁ  ndings. This work has emphasized what 
‘normal’ people say without exploring the actual experiences of people with mental illness themselves about the behaviour of nor-mal people towards them. Further it has been assumed that such statements (usually on knowledge, attitudes, or behavioural inten-tions) are congruent with actual behaviour, without assessing such behaviour directly. Such research has usually focussed on hypo-thetical rather than real situations, neglecting emotions, and the social context, thus producing very little guidance about interven-

tions that could reduce social rejection. In short, most work on 
stigma has been beside the point.
Global patterns
Do we know if discrimination varies between countries and cultures? The evidence here is stronger, but still frustratingly patchy.
(36) Although studies on stigma and mental illness have 
been carried out in many countries, few have been comparison of two or more places, or have included non-Western nations.
(37)
In Africa one study described attitudes to mentally ill people in 
rural sites in Ethiopia. Among almost 200 relatives of people with diagnoses of schizophrenia or mood disorders, 75 per cent said that they had experienced stigma due to the presence of mental illness in the family, and a third (37 per cent) wanted to conceal the fact that a relative was ill. Most family members (65 per cent) said that praying was their preferred of treating the condition.
(38) Among 
the general population in Ethiopia schizophrenia was judged to be

(38) Among 
the general population in Ethiopia schizophrenia was judged to be 
the most severe problem, and talkativeness, aggression, and strange behaviour were rated as the most common symptoms of mental illness.
(39) The authors concluded that it was important to work 
closely with traditional healers.
In South Africa,(40,41)  a survey was conducted of over 600 mem-
bers of the public on their knowledge and attitudes towards people with mental illness.
(42) Different vignettes, portraying depression, 
schizophrenia, panic disorder, or substance misuse were presented to each person. Most thought that these conditions were either related to stress or to a lack of willpower, rather than seeing them as medical disorders.
(43) Similar work in Turkey,(44) and in Siberia 
and Mongolia(45) suggests that people in such countries may be 
more ready to make the individual responsible for his or her men-tal illness and less willing to grant the beneﬁ  ts of the sick role.

Most of the published work on stigma is by authors in the 
USA and Canada,
(11,27,46,47) but there are also a few reports from 
elsewhere in the Americas and in the Caribbean.(48) In a review of 
studies from Argentina, Brazil, Dominica, Mexico, and Nicaragua, mainly from urban sites, a number of common themes emerged. The conditions most often rated as ‘mental illnesses’ were the psychotic disorders, especially schizophrenia. People with higher levels of education tended to have more favourable attitudes to people with mental illness. Alcoholism was considered to be the most common type of mental disorder. Most people thought that a health professional needs to be consulted by people with mental illnesses.
(49)
A great deal of work has studied the question of stigma

(49)
A great deal of work has studied the question of stigma 
towards mentally ill people in Asian countries and cultures.(50–52)
Within China,(53) a large scale survey was undertaken of over 
600 people with a diagnosis of schizophrenia and over 900 family members.
(54) Over half of the family members said that stigma 
had an important effect on them and their family, and levels of stigma were higher in urban areas and for people who were more highly educated.
In the ﬁ  eld of stigma research we ﬁ  nd that schizophrenia is the

In the ﬁ  eld of stigma research we ﬁ  nd that schizophrenia is the 
primary focus of interest. It is remarkable that there are almost no studies, for example, on bipolar disorder and stigma. A comparison of attitudes to schizophrenia was undertaken in England and Hong Kong. As predicted, the Chinese respondents expressed more nega-tive attitudes and beliefs about schizophrenia, and preferred a more social model to explain its causation. In both countries most par-ticipants, whatever their educational level, showed great ignorance about this condition.
(55) This may be why most of population in 
Hong Kong are very concerned about their mental health and hold rather negative views about mentally ill people.
(56) Less favourable 
attitudes were common in those with less direct personal contact with people with mental illness (as in most Western studies), and by women (the opposite of what has been found in many Western reports).
(57)

(57)
Little research on stigma has been conducted in India. Among 
relatives of people with schizophrenia in Chennai (Madras) in Southern India, their main concerns were: effects on marital pros-pects, fear of rejection by neighbours, and the need to hide the condition from others. Higher levels of stigma were reported by women and by younger people with the condition. 
(58) Women 
who have mental illness appear to be at a particular disadvantage in India. If they are divorced, sometimes related to concerns about heredity,
(59) then they often receive no ﬁ  nancial support from their 
former husbands, and they and their families experience intense distress from the additional stigma of being separated or divorced.
(60)SECTION 1  the subject matter of and approach to psychiatry

7
In Japan mental illnesses are seen to reﬂ  ect a loss of control, and 
so are not subject to the force of will power, both of which lead to a sense of shame.
(61–63)  Although, it is tempting to generalize about 
the degree of stigma in different countries, reality may not allow such simpliﬁ  cations. A comparison of attitudes to mentally ill 
people in Japan and Bali, for example showed that views towards people with schizophrenia were less favourable in Japan, but that people with depression and obsessive-compulsive disorder were seen to be less acceptable in Bali.
(64)
What different countries do often share is a high level of ignorance 
and misinformation about mental illnesses. A survey of teachers’ opinions in Japan and Taiwan showed that relatively few could describe the main features of schizophrenia with any accuracy. The general proﬁ  le of knowledge, beliefs, and attitudes was similar to

that found in most Western countries, although the degree of social rejection was somewhat greater in Japan.
(65)
In a unique move aimed to reduce social rejection, the name 
for schizophrenia has been changed in Japan. Following a decade of pressure from family member groups, including Zenkaren, the name for this condition was changed from seishi buntetsu 
byo (split-mind disorder) to togo shiccho sho  (loss of co-ordination 
disorder).
(66,67) The previous term went against the grain of 
traditional, culturally-valued concepts of personal autonomy, as a result of which only 20 per cent of people with this condi-tion were told the diagnosis by their doctors.
(68–70)  There are 
indications from service users and family members that the new term is seen as less stigmatizing and is more often discussed openly.
Little is written in the English language literature on stigma in 
Islamic communities, but despite earlier indications that the intensity of stigma may be relatively low,

(52) detailed studies 
indicate that on balance, it is no less than we have seen described elsewhere.
(71–74)  A study of family members in Morocco found 
that 76 per cent had no knowledge about the condition, and many considered it chronic (80 per cent), handicapping (48 per cent), incurable (39 per cent), or linked with sorcery (25 per cent). Most said that they had ‘hard lives’ because of the diagnosis.
(75)
Turning to religious authority ﬁ  gures is reported to be common 
in some Moslem countries.(76,77) Some studies have found that 
direct personal contact was not associated with more favour-able attitudes to people with mental illness,
(78,79)  especially 
where behaviour is seen to threaten the social fabric of the community.
(80,44)
What sense can we make of all these fragments of information?

(80,44)
What sense can we make of all these fragments of information? 
Several points are clear. First there is no known country, society, or culture in which people with mental illness are considered to have the same value and to be as acceptable as people who do not have mental illness. Second, the quality of information that we have is relatively poor, with very few comparative studies between coun-tries or over time. Third, there do seem to be clear links between popular understandings of mental illness, if people in mental dis-tress want to seek help, and whether they feel able to disclose their problems.
(81) The core experiences of shame (to oneself and for 
others) and blame (from others) are common everywhere stigma has been studied, but to differing extents. Where comparisons with other conditions have been made, then mental illnesses are more, or far more, stigmatized,

(82,83) and have been referred to as the 
‘ultimate stigma’ (9). Finally, rejection and avoidance of people with 
mental illness appear to be universal phenomena.Conclusions
If we deliberately shift focus from stigma to discrimination, there are a number of distinct advantages. First attention moves from attitudes to actual behaviour, not if an employer would  hire a person 
with mental illness, but if he or she does. Second, interventions can 
be tried and tested to see if they change behaviour towards people with mental illness, without necessarily  changing knowledge or 
feelings. The key candidates as active ingredients to reduce stigma are: (i) at the local level, direct social contact with people with mental illness;
(84–86) and (ii) social marketing techniques at the 
national level. Third, people who have a diagnosis of mental illness can expect to beneﬁ  t from all the relevant anti-discrimination

national level. Third, people who have a diagnosis of mental illness can expect to beneﬁ  t from all the relevant anti-discrimination 
policies and laws in their country or jurisdiction, on a basis of parity with people with physical disabilities. Fourth, a discrimina-tion perspective requires us to focus not upon the ‘stigmatized’ but upon the ‘stigmatizer’ . In sum, this means sharpening our sights upon human rights, upon injustice, and upon discrimination as actually experienced by people with mental illness.
(7,24,87,88)
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Hinshaw, S. (2007). The mark of shame: stigma of mental illness and an 
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9
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185, 277–9.1.2 public attitudes and the challenge of stigma

1.3
Psychiatry as a worldwide 
public health problem
Contents
public health issue
 1.3.2 Transcultural psychiatry
1.3.1 Mental disorders as a 
worldwide public health issue
Magnitude and burden of mental disorders
The twentieth century has witnessed signiﬁ  cant improvements in 
somatic health in most countries. A number of key public health threats have been eradicated or brought under control under the leadership of WHO. Priority was given to communicable diseases in view of their inherent potential to spreading.
At the present time, a focus on non-communicable diseases and

At the present time, a focus on non-communicable diseases and 
mental health would now appear as the next natural step in public health priorities. In the case of mental health, this is due to the capacity of mental disorders to proliferate not only as a result of complex and multiple biological, psychological but also social determinants. WHO estimates that at any given time 450 million people suffer from some form of mental or brain disorder, includ-ing alcohol and substance use disorders. In other words, one in four of the world’s population suffer from different forms of 
mental, behavioural, and neurological disorders.
(1)
The World Development Report: investing in health(2) and the 
development of the disability-adjusted life-year for estimating the global burden of disease, including years lost because of disability
(3,4)

(3,4)
and the World Health Report 2001, have all raised the awareness of the global burden of mental disorders. Mental disorders already account for more than 13.46 per cent of the GBD. Furthermore, it is estimated that by the year 2015, the GBD from all neuropsychiatric illnesses will reach 14.14 per cent and by 2030, 14.42 per cent. 
According to WHO, mental disorders accounted for 6 of the 20 leading causes of disability worldwide for  the 15–44 age group, the most productive section of the population.
(1) While a greater

(1) While a greater 
proportion of the burden is found in high-income countries (21.4 per cent) including those with formerly socialist economies (16.4 per cent), low- and middle-income countries are greatly affected and are likely to see a disproportionately large increase in the burden attributable to mental disorders in the coming decades as infectious diseases are brought under better control and as the population ages. The growing burden of mental, neurological, and substance use disorders is exacerbated in low and middle-income countries due to a projected increase in the number of young people entering the age of risk for the onset of certain mental disorders. An estimated 849 000 people commit suicide every year. This ﬁ  gure represents 1.4 per cent of the global burden of disease as

estimated using Disability Adjusted Life Y ears (DALY) methodology. The proportion of the global disease burden due to suicide varies from 0.2 per cent in Africa up to 2.5 per cent in the Western Paciﬁ  c 
region. In the European, South East Asian, and Western Paciﬁ  c 
regions, this proportion exceeds the world average. Suicide among young people is of signiﬁ  cant concern; in some regions, suicide is 
the third leading cause of death in the age group of 15–35 years. Suicide is the leading cause of death for this age group in China and the second in the European region. Alcohol consumption alone is responsible for 4 per cent of the global disease burden.
(5) In 2000,

(5) In 2000, 
the global use of alcohol was estimated to have caused 1.8 million deaths or 3.2 per cent of the total deaths from all causes that year. It is estimated that 2.2 million people died from alcohol-related causes in 2005 and increase of 22 per cent from 2000. The popula-tion of injecting drug users comprises approximately 10 million people worldwide. Globally, 4–12 per cent of all HIV cases are due to injection drug use, a driving force behind the HIV/AIDS epidemic in many parts of the world.
Economic and social costs of 
mental disorders
The economic and social costs of mental disorders fall on societies, 
governments, people with mental disorders, and their carers and families. Given the long-term nature of mental disorders, the most

11
evident economic burden is that of direct treatment costs. For 
example, the most important contributor to direct costs of depres-sion is hospitalization, accounting for around half of the total in the United Kingdom and three-quarters in the United States.
(6)
However a common ﬁ  nding from studies of the economic burden 
of mental disorders in high-income countries is that the ‘indirect’ costs of lost productivity and premature mortality outweigh the ‘direct’ costs of treatment and care.
(7) Three recent mental health 
economic studies carried out in India have likewise shown that lost production and other time costs greatly exceed the costs of targeted clinical intervention.
(8–10)
In most countries, families bear a signiﬁ  cant proportion of these

(8–10)
In most countries, families bear a signiﬁ  cant proportion of these 
economic costs because of the absence of publicly funded compre-hensive mental health service networks. However, ulti mately gov-ernments and societies pay a price in terms of reduced national income and increased expenditure on social welfare programmes. Thus, the economic logic for societies and countries is simple: treating mental disorders is expensive but leaving them untreated can be more expensive.
In addition to the obvious suffering caused by mental disorders

In addition to the obvious suffering caused by mental disorders 
there is a hidden burden of stigma and discrimination and human rights violations. Rejection, unfair denial of employment opportu-nities and discrimination in access to services, health insurance, and housing are common as are violations of basic human rights and freedoms, as well as denials of civil, political, economic, and social rights, in both institutions and communities. Much of this goes unreported and therefore the burden remains unquantiﬁ  ed. 
Families and primary care providers also incur social costs, such as the emotional burden of looking after disabled family members, diminished quality of life, social exclusion, stigmatization, and loss of future opportunities for self-improvement.
Global resources for mental health
The WHO survey of mental health resources (Project Atlas) highlighted the huge existent gap between the burden of mental disorders and available resources.
(11,12)

(11,12)
Mental health policy and legislation
Mental health services and strategies must be well coordinated with other services, such as social security, education, and public inter-ventions in employment and housing through an adequate mental health policy. In spite of this, only 62 per cent of countries have a policy in the mental health ﬁ  eld (see Table 1.3.1.1). Mental health 
legislation is essential to guarantee the dignity of patients and protect their fundamental human rights, though 22 per cent of countries do not have legislation in the ﬁ  eld of mental health.
Mental health budget
In spite of the importance of mental health burden in the world 
(representing more than 13.46 per cent of global burden of diseases), out of only 101 countries that reported having a speciﬁ  c

(representing more than 13.46 per cent of global burden of diseases), out of only 101 countries that reported having a speciﬁ  c 
budget, 25 per cent spend less than 1 per cent of the total health budget on mental health (Fig. 1.3.1.1).
Methods of ﬁ  nancing mental health care
The tax-based method is the preferred method for ﬁ  nancing men-
tal health care present in 63 per cent of countries (Fig. 1.3.1.2), while all the countries with out-of-pocket ﬁ  nancing as the primary 
method are low- or middle-income countries. However, families of people with severe chronic mental disorders are often among the poorer and, in addition to the family burden, can access to basic mental health care.
Community care for mental health

Community care has a better effect than institutional treatment on the outcome and quality of life of individuals with chronic mental disorders. Globally, 68 per cent of countries reported to have at least some community care facilities for mental health. Community care facilities in mental health are only present in 52 per cent of the low-income countries versus 97 per cent of high-income countries.
Though community-based services are recognized to be most 
effective, 65 per cent of all psychiatric beds are still in mental hos-pitals—eating away the already meagre budgets while providing largely custodial care in an environment that violates basic human rights of inmates.
(10)Fig. 1.3.1.1 Percentage of total health budget spent on mental 
health—countries (%) ( N = 101). Taken from The World health report 
2001–Mental Health: New Understanding, New Hope © 2001, World Health Organization, www.who.int25%
39%28%8%
0–1%
1–5%
5–10%
>10%

39%28%8%
0–1%
1–5%
5–10%
>10%
Percentage of total health
budget spent on mental health 
Table 1.3.1.1  Policy and legislation on mental health in WHO 
regions and the world—countries (%)
WHO regions Policy (N: 190) Legislation (N: 173)
Africa 50% 80%
Americas 73% 75%Eastern Mediterranean 73% 57%Europe 71% 92%South-East Asia 55% 64%Western Paciﬁ  c 48% 76%World 62% 78%
Source: The World health report 2001–Mental Health: New Understanding, New Hope, 
© 2001, World Health Organization, www.who.int  Fig. 1.3.1.2 Methods of ﬁ  nancing mental health care in the world—countries 
(%) ( N = 180). Taken from The World health report 2001–Mental Health: New 
Understanding, New Hope, © 2001, World Health Organization, www.who.int
1.3.1 mental disorders as a worldwide public health issue

SECTION 1  the subject matter of and approach to psychiatry 12
Psychiatric beds
The distribution of psychiatric beds by setting across different 
income countries also varies. In low-income countries 74 per cent of the psychiatric beds are located in mental hospitals, while in high-income countries only 55 per cent. Across different regions, south-east Asia has 83 per cent of its psychiatric beds in mental hospitals compared with 64 per cent in the European region (see Table 1.3.1.2). The Western Paciﬁ  c region has the highest propor-

tion of psychiatric beds in general hospitals (35 per cent), followed by Europe with 22 per cent of their total psychiatric beds. In approximately 41 per cent of countries there is less than one psychiatric bed per 10 000 of the population. The proportion of beds which are not located in mental hospitals or in general hospitals includes those in private and military hospitals, hospitals for special groups of population or long-term rehabilitation centres.
Professionals working in mental health
All the countries in the south-east Asia region and most of countries in the African region have less than one psychiatrist per 100 000 population compared to 10 psychiatrist per 100 000 populations in the European region (see Table 1.3.1.3).
The median number of psychiatric nurses per 100 000 popula-
tion varies from 0.10 in the south-east Asia region to 25 in the European region.
The median number of psychologists in mental health per 100 000

population varies from 0.03 in the south-east Asia and Western Paciﬁ  c region to 3.10 in the European region and 2.80 in the 
American region.
In the world there is less than one psychologist per 100 000 pop-
ulation in 61.6 per cent of countries and in low-income countries almost all the population has access to less than one psychologist 
per 100 000.
The median number of social workers working in mental health 
per 100 000 population varies from 0.04 in the south-east Asian region to 1.50 in the European region. In about 64 per cent of countries there is less than one social worker per 100 000 population. In the African and Eastern Mediterranean regions more than 85 per cent of the population has access to less than one social worker per 100 000 population.Treatment gap for mental disorders

A large proportion of the individuals who suffer from mental disorders do not receive any health care for their condition. The treatment gap for most mental disorders is high. According to a recent review done by WHO from published sources, originating from the United States, Europe, Brazil, Chile, China, India, Zimbabwe, and others,
(13) the percentages of people in need for 
treatment not receiving it are as follows (see Table 1.3.1.4).
Improving mental health care
The mental health infrastructure and services in most countries is grossly insufﬁ  cient for the large and growing needs. In order to 
deliver a high standard of mental health treatment and care, WHO emphasizes the adoption of an integrated system of service delivery which attempts to comprehensively address the full range of psychosocial needs of people with mental disorders. A number of policy recommendations for service organizations have been highlighted in the World Health Report 2001.
(1) They include

(1) They include 
(i) shifting care away from large psychiatric hospitals, (ii) develop-ing community mental health services, and (iii) integrating mental health care into general health services.Table 1.3.1.2  Psychiatric beds per 10 000 population and 
proportion of psychiatric beds in mental hospitals in WHO regions and the world ( N = 185)
WHO regions Median per 10,000 
populationMental hospitals (%)
Africa 0.34 73.0
Americas 2.60 80.6Eastern Mediterranean 1.07 83.0Europe 8.00 63.5South-East Asia 0.33 82.7Western Paciﬁ  c 1.06 60.1World 1.69 68.6
Source: Taken from The World health report 2001–Mental Health: New Understanding, 
New Hope, © 2001, World Health Organization, www.who.int
Table 1.3.1.3  Median number of psychiatrists, psychiatric nurses, psyc hologists and social workers working in mental health per 100 000 
population in WHO regions and the world
WHO regions Psychiatrists (N=176) Psychiatric nurses (N=187) Psychologists in mental 
health (N=177)Social workers in

health (N=177)Social workers in 
mental health (N=161)
Africa 0.04 0.2 0.05 0.05
Americas 2 2.6 2.80 1.00Eastern Mediterranean 0.95 1.25 0.60 0.40Europe 9.8 24.8 3.10 1.50South-East Asia 0.2 0.1 0.03 0.04Western Paciﬁ  c 0.32 0.5 0.03 0.05World 1.2 2 0.60 0.40
Source: Taken from The World health report 2001–Mental Health: New Understanding, New Hope, © 2001, World Health Organization, www.who.int

13
Essentially, ethical and scientiﬁ  c considerations have given impe-
tus to the movement to transfer mental health care from mental hospitals to primary health care, general hospitals, and a range of community services in the expectation of enhancing accessibility and acceptability of services, achieving better ‘mental’ and ‘physical’ health outcomes, and also a better rationalization of resources.
A large part of mental health care can be self-managed and/or 
managed by informal community mental health services and low-cost resources can be made available in the community to this effect. Where additional expertise and support is needed a more formal-ized network of services is required. In ascending order these include primary care services, followed by psychiatric services based in gen-eral hospitals and formal community mental health services and lastly by specialist and long stay mental health services.
The mental health ﬁ  eld is developing rapidly. There is an evolv-

ing information base to guide policy, legislation, service develop-ment, and clinical practice. However, there remains a gap between what we know in terms of what works and what is actually occur-ring in practice in countries around the world. This gap needs to be closed by continued advocacy efforts to raise mental health on the agenda of governments, by continued dissemination of informa-tion on effective policies, service development and clinical practice, and the dissemination of international human right standards.
Acknowledgements
M. Garrido Cumbrera has contributed to this publication providing signiﬁ  cant comments and technical assistance during the prepara-
tion of this manuscript.
Disclaimer

B. Saraceno is a staff member of the World Health Organization. The author alone is responsible for the views expressed in this pub-lication and they do not necessarily represent the decisions, policy or views of the World Health Organization.
WHO Mental Health website: http://www.who.int/mental_health/en/
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2001: mental health: new understanding, new hope . World Health 
Organization, Geneva.
2. World Bank (1993). World Development Report: investing in health .
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Oxford University Press, New Y ork. 3. Murray, C.J.L. and Lopez, A.D. (1996). The global burden of diseases: 
a comprehensive assessment of mortality and disability from diseases, injuries and risk factors in 1990 and projected to 2020 . Harvard School of 
Public Health, World Health Organization and World Bank, Boston.
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reﬁ ning the global burden of disease approach: a response to Williams. 
Health Economics ,9, 69–82.
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 7. Hu, T-W. (2004). An International Review of the Economic Costs 
of Mental Illness. Disease Control Priorities Project. Working Paper No. 31. University of California, Berkeley. Available at: http://www.dcp2.org/ﬁ  le/45/wp31.pdf
 8. Chisholm, D., Sekar, K., Kumar, K.K., et al. (2000). Integration 
of mental health care into primary care. Demonstration cost-outcome study in India and Pakistan. The British Journal of Psychiatry ,
176, 581–8.
 9. Patel, V ., Chisholm, D., Rabe-Hesketh, S., et al.  (2003). Efﬁ  cacy and cost-
effectiveness of drug and psychological treatments for common mental disorders in general health care in Goa, India: a randomised, controlled trial. Lancet ,361(9351), 33–9.
10. Srinivasa Murthy, R., Kishore Kumar, K.V ., Chisholm, D., et al.  (2005).

10. Srinivasa Murthy, R., Kishore Kumar, K.V ., Chisholm, D., et al.  (2005). 
Community outreach for untreated schizophrenia in rural India: a follow-up study of symptoms, disability, family burden and costs. 
Psychological Medicine ,35(3), 341–51.
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12. Saxena, S., Sharan, P ., Garrido Cumbrera, M., et al.  (2006). World 
Health Organization’s mental health atlas 2005: implications for policy 
development. World Psychiatry ,5(3): 179–84.
13. Kohn, R., Saxena, S., Levav, I., et al.  (2004). The treatment gap in 
mental health care. Bulletin of the World Health Organization ,82(11): 
856–66.
1.3.2 Transcultural psychiatry
Clinical relevance of transcultural 
psychiatry
With the mass movements of populations that have characterized

856–66.
With the mass movements of populations that have characterized 
the second half of the twentieth century, there can be few psychia-trists who do not encounter members of an ethnic minority group in their practice. The principles of transcultural psychiatry are obviously of relevance to this type of psychiatrist–patient interac-tion, but they are also of central importance even when the psychiatrist and patient share the same ethnic background. This is 
because within a particular ethnic group there are invariably many subcultures, for example based on religious afﬁ  liation, which

because within a particular ethnic group there are invariably many subcultures, for example based on religious afﬁ  liation, which 
encompass a diversity of beliefs. It is essential that the psychiatrist be aware of the common belief systems likely to be encountered, not simply to enhance rapport with patients and relatives, but in order to avoid serious mistakes in ascribing pathology to experi-ences that are accepted as normal by the subculture. For example, it is important to be aware that between 10 and 17.5 per cent of the Table 1.3.1.4  Treatment gap for some mental and substance use 
disorders
Schizophrenia 32.2%
Depression 56.3%Bipolar disorder 50.2%Panic disorder 55.9%Obsessive compulsive disorder 57.3%Alcohol abuse and dependence 78.1%
New Hope, © 2001, World Health Organization, www.who.int1.3.2 transcultural psychiatry

SECTION 1  the subject matter of and approach to psychiatry 14
general population report experiencing psychotic symptoms.(1,2)
The political repercussions of ignorance of such subcultural phe-
nomena are illustrated by the accusations of misdiagnosis of Black patients by White psychiatrists which have come from both outside and within the profession. It is somewhat reassuring that the only published scientiﬁ  c study of this contention fails to support it.
(3)
There are two main streams of thought and enquiry that have

(3)
There are two main streams of thought and enquiry that have 
shaped the development of transcultural psychiatry: social anthro-pology and psychiatric epidemiology. In a number of ways these disciplines are opposed; the former is concerned with qualitative data and emphasizes cultural relativity (see Chapter 2.6.2.), while the latter relies on quantitative data and prioritizes a search for universal disease categories (see Chapter 2.7). The tools of the epidemiologist are standardized interview schedules which are linked with deﬁ  nitions of symptoms and signs, and rules for 
reaching a diagnosis. These have been introduced in an attempt to reduce the subjectivity of the psychiatrist’s judgement to a minimum. By contrast, it is the person’s subjective experience of illness that is the prime focus of the anthropologist. Consequently the use of standardized psychiatric interviews has been criticized by anthropologists as imposing a western biomedical model of

disease on the rich variety of experience of illness and distress. The 
two approaches are not mutually exclusive and are best viewed as contributing complementary material to our understanding of psychiatric morbidity.
(4)
The contribution of psychiatric 
epidemiology
Cultural inﬂ  uences on the psychoses
Epidemiologists have been keen to discover whether psychiatric 
conditions are universal and appear with the same incidence across human populations. Universality would minimize the role of culture in shaping the form of a condition, while a uniform inci-dence would indicate that biological factors played a major role in aetiology. Schizophrenia has been the focus of many epidemiologi-cal surveys, especially the cross-national studies conducted by the World Health Organization (WHO). The International Pilot Study of Schizophrenia
(5) showed that it was possible to conduct a psy-
chiatric epidemiological study across a wide variety of cultures and languages.

(6) The use of standardized assessment and diagnostic 
techniques revealed that the core symptoms of schizophrenia were subject to few cultural variations. The most striking difference in the form of the illness was that catatonic symptoms were relatively frequent in patients from developing countries, but rare in the other centres.
The success of this study led to an even more ambitious project—
the Determinants of the Outcome of Severe Mental Disorders. The main aim was to collect epidemiologically based samples of psychotic patients making a ﬁ  rst contact with health services in centres 
around the world. It was found that the incidence of narrowly deﬁ ned schizophrenia was remarkably uniform across a diversity 
of countries.
(7) However, when patients with a broad diagnosis

(7) However, when patients with a broad diagnosis 
of schizophrenia but lacking the core Schneiderian symptoms were considered, the incidence rates across centres showed a three-fold difference which was highly signiﬁ  cant. This suggests that 
socio-cultural factors are likely to play a much greater role in the aetiology of non-Schneiderian schizophrenia than in the narrowly deﬁ ned form, although the nature of these factors remains to be 
determined.
Dramatic differences in outcome at a 2-year follow-up were 
found, patients with schizophrenia in developing centres faring considerably better than those in developed centres despite a paucity of psychiatric personnel and facilities. This was not explained by a higher proportion of cases with an acute onset in the developing centres, raising intriguing questions about the beneﬁ  cial aspects of

traditional cultures. Explanations that have been proposed include beliefs that the causes of illness are external to the patient, the low demands for productivity and punctuality in an agrarian economy enabling the employment of disabled patients, and the quality of traditional family life. Only the latter has been investigated and appears to make an important contribution, since family carers in India are far less critical and more tolerant of patients with schizo-phrenia than their counterparts in Britain.
(8)
The existence of relatively large populations of people of ethnic 
minority status in developed countries has facilitated the study of cultural inﬂ  uences on psychoses. Such research has revealed a 
remarkably elevated incidence of both schizophrenia and mania in some of these groups.
(9,10) Of a number of possible explanations, 
the most likely lie in the social environment.(11)
Mania has been the focus of much less transcultural research

Mania has been the focus of much less transcultural research 
than schizophrenia, but what little there is suggests that psychotic experiences are more common in Nigerian and African–Caribbean patients than in patients from European countries.
(12,13)
Cultural inﬂ  uences on the neuroses
(a) Variations in frequency across cultures
Whereas neither the form nor the incidence of psychoses vary 
much across cultures, neuroses show dramatic variations in both respects. So-called culture-bound syndromes are an extreme example of variation in frequency since it is claimed that they are conﬁ  ned to speciﬁ  c cultural groups (see Chapter 4.16.). It is an 
error to think of these as exotic manifestations in traditional soci-eties, since eating disorders, while increasingly common in devel-oped countries are infrequent elsewhere.
(14) Even with common

(14) Even with common 
conditions such as depression, the range of prevalence rates from studies across cultures is extremely wide.
(15) This is partly attribut-
able to a greater focus on bodily symptoms in patients in develop-ing countries. The signiﬁ  cance of somatic symptoms may well be 
missed by standardized interviews designed to detect the cognitive experiences of depression.
The emphasis on the measurement of prevalence of neuroses as

The emphasis on the measurement of prevalence of neuroses as 
opposed to incidence is due to the small proportion of new cases of neurosis that present to psychiatric services. In order to detect the majority of new cases of neuroses it is necessary to conduct popu-lation surveys, which are costly in terms of time and trained per-sonnel. The few population surveys that have been conducted in both developed and developing countries using the same methods of interviewing and case ascertainment have shown either no dif-ference in the prevalence of neuroses
(16,17)  or a higher rate in the 
developing country.(18,19)
(b) Variations in form across cultures

One of the most striking transcultural aspects of the neuroses is the great variation in the frequency of classical conversion hysteria. Whereas this condition is rarely seen in psychiatric and neurologi-cal services in developed countries today, it is still a common form

15
of presentation in developing countries.(20) This is another mani-
festation of the tendency to present emotional distress in bodily terms that prevails in those cultures. Somatization is by no means uncommon in patients in developed countries, particularly in indi-viduals of lower socio-economic status, but somatic symptoms are more likely to dominate the picture in patients in a developing country. This is determined partly by beliefs about illness (see Chapter 2.6.2.) and partly by mutual expectations of patients and doctors and of traditional healers, who treat the majority of people with neuroses in developing countries.
Contributions of anthropology
Help-seeking behaviour

In general people seek help from healers who hold the same beliefs as they do (see Chapter 7.3). Traditional healers in developing countries have the advantage of sharing the same belief system about illness with their clients, so that they can take for granted a great deal of common ground and do not need to embark on long explanations. Clients of traditional healers often present their dis-tress in terms of somatic symptoms. Skilled healers are adept at understanding the relationship problems that underlie the client’s bodily complaints, and their prescription of rituals is aimed at involving the client’s social network and regularizing relation-ships.
(21) Problems in communication arise when the patient brings 
somatic symptoms to the western trained doctor, who may fail to detect the emotional distress generating the symptoms
(22) and is 
unable to recognize the relationship difﬁ  culties that have prompted 
the comlaints.

(22) and is 
Traditional healers are by no means conﬁ  ned to developing coun-
tries or to ethnic minority groups in developed countries. Alternative medicine ﬂ  ourishes where western biomedicine is per-
ceived by the public to be ineffective, and psychiatry is one of those areas. Patients with psychiatric conditions are very likely to seek help from acupuncture, spiritual healing, homeopathy, or herbal remedies, in addition to consulting the general practitioner or psy-chiatrist. Sympathetic questioning of psychiatric patients will elicit their use of a number of sources of alternative medicine in their neighbourhood.
The concept of depression
At the same time as the evidence for a biological basis for depression appears to be strengthening, the western concept of depression has been criticized by transcultural researchers. Obeyesekere
(23) considers that each culture has developed its own

(23) considers that each culture has developed its own 
methods for dealing with painful emotions, for example, the Buddhists of Sri Lanka cope with the loss of a loved person by med-itating on the illusory nature of the world of sense, pleasure, and domesticity. Obeyesekere
(23) refers to these coping measures 
as ‘the work of culture’ and views the construction of a disease known as depression as a western cultural resource. Its incorpora-tion into international classiﬁ  cations of diseases could be viewed 
as ‘the imposition of western cultural standards that are presented as universal and inseparable parts of an emerging new world order’ .
(24) If a biological basis for the neuroses was ﬁ  rmly estab-
lished such a formulation could be readily dismissed, but the efﬁ cacy of non-biological treatments for depression and anxiety, 
such as cognitive therapy, couple therapy, and behaviour therapy, indicates that Obeyesekere’s view deserves serious consideration.

such as cognitive therapy, couple therapy, and behaviour therapy, indicates that Obeyesekere’s view deserves serious consideration. 
It represents a speciﬁ  c example of the general premise that western 
biomedicine is itself a cultural construction and needs to be seen as one of many different ways of dealing with the experience of illness and distress.
(24) The achievement of biomedicine in ridding the 
world of smallpox and other fatal diseases is undeniable, but in the ﬁ  eld of psychiatry in particular we need to remain open to the 
ways other cultures have developed for helping people with what we would term psychiatric illness.
Kleinman, A. (1988). Patients and healers in the context of culture: an 
exploration of the borderland between anthropology, medicine and psychiatry . University of California Press, Berkeley.
Swartz, L. (2000). Culture and mental health: a Southern African view .
Oxford University Press, Oxford.

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psychotic symptoms in the general population. Results from the 
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psychiatrist evaluates diagnoses at a London psychiatric hospital. British 
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manifestations, incidence and course in different cultures: a World 
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schizophrenia in North India. II. Distribution of expressed emotion 
components among relatives of schizophrenic patients in Aarhus 
and Chandigarh. British Journal of Psychiatry ,151, 160–5.
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 9. Cantor-Graae, E., Pedersen, C.B., McNeil, T.F., et al.  (2003). Migration as 
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10. Fearon, P ., Kirkbride, J. B., Morgan, C., et al.  (2006) Incidence of 
schizophrenia and other psychoses in ethnic minority groups: results from the MRC AESOP study. Psychological Medicine, 36, 1541–50.
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ethnicity and schizophrenia: a case control study. Social Psychiatry 
and Psychiatric Epidemiology ,37, 329–35.
12. Leff, J.P ., Fischer, M., and Bertelsen, A. (1976). A cross-national 
epidemiological study of mania. British Journal of Psychiatry ,
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13. Makanjuola, R.O. (1982). Manic disorder in Nigerians. British Journal of 
Psychiatry ,141, 459–63.
14. Greenberg, L., Cwikel, J., and Mirsky, J. (2007). Cultural correlates of

14. Greenberg, L., Cwikel, J., and Mirsky, J. (2007). Cultural correlates of 
eating attitudes: a comparison between native-born and immigrant 
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International Journal of Eating Disorders ,
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health care . Wiley, New Y ork.
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20. Wig, N.N. and Pershad, D. (1975–1977). Triennial statistical report .

Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.21. Nichter, M. (1981). Negotiation of the illness experience: ayurvedic 
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1.4
The history of psychiatry 
as a medical specialty
In 1918, Emil Kraepelin wrote:(1)
A hundred years ago, they were practically no alienists. The care of the 
mental patients was nearly everywhere in the hands of head supervi-sors, attendants and administrators of the houses for the mentally ill and the role of the physicians was limited to the treatment of the physical illnesses of the patients.
He pointed out that, in the ﬁ  rst decades of the 19th century, 
many of the books dealing with psychiatric themes were still written by medical doctors, such as Reil (who coined the word psychiatry), who had few contacts with mental patients or even by philosophers and theologians, and that only in the great scientiﬁ  c 
centres had specialists appeared ‘who had decided to spend their life in the study and treatment of mental diseases’ .
The history of psychiatry as a medical specialty has to be distin-

guished from the history of psychiatric medical knowledge which began in ancient Greece with the birth of medicine as a science. For more than 2000 years, only physicians observed and treated mental illnesses, and institutions were created in which the ‘lunatics’ and the ‘insane’ were received. But, as rightly pointed out by Kraepelin, the truth is that psychiatry was not really a medical specialty. One 
can argue about the precise date of the appearance of psychiatry as a speciﬁ  c ﬁ eld of medicine and of the psychiatrist as a specialist,

can argue about the precise date of the appearance of psychiatry as a speciﬁ  c ﬁ eld of medicine and of the psychiatrist as a specialist, 
devoting his professional competence exclusively to the care of the mentally ill. Denis Leigh recognizes that ‘some degree of specializa-tion occurred [in England] among respectable physicians’ in the middle of the eighteenth century when the monopoly of Bethlem was broken and new ‘lunatic hospitals’ , such as St Luke’s were opened.
(2) On the other hand, the American historian Jan Goldstein 
stresses that in France the language, as an exact reﬂ  ection of the 
underlying reality, began to use expressions such as homme spécial
to describe a physician specializing in a branch of medicine such as psychiatry only around 1830.
(3)
Pinel and the birth of psychiatry as a branch 
of medicine
Despite those divergences, it is generally accepted that the work of

(3)
Despite those divergences, it is generally accepted that the work of 
Philippe Pinel constitutes a turning point. His role has several aspects. He is known worldwide as the physician who ‘liberated the insane from their chains’ in a dramatic initiative he started in 1793, 
at the height of the French revolution, at the Bicêtre asylum, and completed 3 years later at the Salpêtrière asylum. However, the reality is more complex.
Pinel, who was born in 1745, had studied medicine, translated 
Cullen’s books into French, and published scientiﬁ  c papers on vari-
ous subjects. He acted as a physician in a small Parisian ‘madhouse’ , the Pension Belhomme, in which wealthy lunatics were conﬁ  ned at 
the request of their families. At that time most of the Parisian insanes were conﬁ  ned for a few weeks in the general hospital––the

the request of their families. At that time most of the Parisian insanes were conﬁ  ned for a few weeks in the general hospital––the 
Hôtel Dieu. If their state did not rapidly improve, they were considered as incurable and send to Bicêtre or the Salpêtrière, built a century before, which also received other social deviants like beggars and prostitutes. Pinel, who was known by his politically inﬂ uential friends for his progressive scientiﬁ  c ideas, was appointed 
physician to Bicêtre. The division for the insane was under the direction of an overseer ( surveillant ), Pussin, who had already 
introduced humanitarian reforms in the care of the patients. Pinel’s 
merit was to approve and systematically develop Pussin’s empirical measures and to propose an explicit scientiﬁ  c theory for their 
mode of action. Inspired by Crichton’s views about the nature of the ‘passions’ by Condillac’s psychology, and by the ideas of Jean-Jacques Rousseau, he created the traitement moral  which

mode of action. Inspired by Crichton’s views about the nature of the ‘passions’ by Condillac’s psychology, and by the ideas of Jean-Jacques Rousseau, he created the traitement moral  which 
he claimed to be effective with patients previously considered as incurably ill.
The improvement of the conditions in which the insane were

The improvement of the conditions in which the insane were 
cared for, supported and expanded by Pinel, was not an isolated French phenomenon. In Tuscany, Chiarugi in 1789 had already asserted that the basis of the extensive reforms he had introduced in the local asylum for the insane was that ‘it is a supreme moral duty and a medical obligation to respect the mental patient as a person’ . In England, where public had been shocked by the inhu-man treatment to which King George III had been submitted dur-ing his mental illness; and where, a pious Quaker, William Tuke, deeply affected by the conditions in which the wife of a member of the Society of Friends had died in Y ork lunatic asylum, decided to set up a special institution under the government of the Friends ‘for the care and accommodation of their own members’ . At the Retreat, opened in 1796 near Y ork, physical restraints were largely abolished, and religious and moral values were emphasized in relations with the patients.

SECTION 1  the subject matter of and approach to psychiatry 18
Chiarurgi’s reforms did not survive the upheavals caused by sub-
sequent wars and the political divisions of Italy, and Tuke’s creation 
of the Retreat had not been prompted by medical considerations but was the expression of religious humanitarian purposes. The role played by Pinel was decisive, not so much because of the changes he promoted in the conditions of the patients, although they had a profound inﬂ  uence, but because he made the study and 
treatment of mental disorders a branch of medicine.
In 1801, Pinel published the Medico-philosophical Treatise on 
Mental Alienation . In it, he presented the various clinical manifes-

tations he had observed; proposed a simple nosological system largely borrowed from older authors; examined possible aetiologi-cal factors; and described his ‘moral treatment’ in detail. The book has remained a landmark in the history of psychiatry, even being considered by the philosopher Hegel as a ‘moment of capital importance in the history of humanity’ . For Pinel, insanity was a disease and the patient affected by it remained, despite the loss of his reason, a human being. Its study, like the rest of medicine, had to be ‘a science which consists of carefully observed facts’ . Goldstein
(3) has shown that Pinel’s main preoccupation was to 
prove this scientiﬁ  c nature of the new medical specialty by repudi-

ating the previous practices of the ‘empirics’ and ‘charlatans’––the two terms being practically synonymous. He had accepted the method Pussin had developed empirically and transformed it in his moral treatment by providing a scientiﬁ  c theory of its mode of 
action. A curiously premonitory aspect of his emphasis on the necessity of a scientiﬁ  c methodology is to be found in his Tables to 
Determine How Probable is the Curability of Alienation , published 
in 1808. He provided statistical data on the efﬁ  cacy of his therapeu-
tic method according to the types of mental disorders and in comparison with spontaneous evolution, and concluded that med-icine can only be a true science through the use of the calculus of probability!
Psychiatry as a profession: Esquirol 
and the clinical approach
If, because of the international inﬂ  uence of the ideas expressed in

If, because of the international inﬂ  uence of the ideas expressed in 
his book, Pinel is the founder of psychiatry as a medical discipline, he was not a psychiatric specialist in the strict meaning of the term. Although he retained his position at the Salpêtrière until his death in 1826 and is known today for his contributions to mental medicine, he had many other medical interests which gave him, in his time, a leading position among the Paris physicians; his Philosophical Nosology , published in 1796 and a classical reference for

several decades, deals with general pathology. The case of his pupil and successor, Esquirol, who became the prototype of the psychiat-ric specialist was very different. At the Salpêtrière he was only in charge of the ‘section of the insane’ . He was later appointed medical director of the Charenton psychiatric asylum near Paris and owned in addition a small clinic, in which he treated his private patients. 
All his activities were exclusively dedicated to the study and treat-
ment of mental disorders and the teaching of psychiatry. His book, On Mental Diseases  published in 1838, in which he collected his 
previous publications, acquired a fame as great as Pinel’s Treatise .

In 1913, Karl Jaspers recognized that the later great representatives of German psychiatry, such as Griesinger and Kraepelin, were strongly indebted to Esquirol. He, and the school he founded, effectively developed one of the basic tenets of the new medical specialty. For Esquirol, careful objective observation and analysis

of the symptoms and the behaviour of the patients were funda-mental. He originated the descriptive clinical approach expanded by his pupils. Even more than Pinel, he was suspicious of unproved theories and when he eventually suggested relations between path-ogenic factors and syndromes, he remained extremely cautious in his interpretations. Zilboorg, the psychoanalytically oriented historian of psychiatry, has accused this predominantly descriptive approach of creating a ‘psychiatry without psychology’ because, lacking psychodynamic concepts, its attempted objectivity remained at an allegedly superﬁ  cial level.
(4) The truth is that it laid the foundations 
of the present description of the mental disorders. The ‘atheoretical’ descriptive approach adopted in the present nosological systems—both the American Diagnostic and Statistical Manual  and the 
International Classiﬁ  cation of Diseases —whose proclaimed purpose

International Classiﬁ  cation of Diseases —whose proclaimed purpose 
is to emphasize the medical character of psychiatry is, in this respect, a return to Esquirol’s principles.
The social aspects of psychiatry 
and the asylum system
By the end of the eighteenth century it was recognized that the 
study of mental alienation was part of medicine. However, mental diseases were of such a nature that it was not possible to treat the insane in the same conditions as patients affected by other diseases. Their most obvious manifestations had social consequences. According to the prevailing philosophical view, the mentally ill were deprived of free-will by their illness. In practice, they were unable to participate in the normal life of the society and were often considered as potentially dangerous. Because of this, they had generally been conﬁ  ned in madhouses of various kinds. One of the

aspects of the reforms initiated by Pinel had been to make more explicit the difference in nature between the socially deviant behav-iour of the insane, which, being the consequence of an illness, belonged exclusively to medicine, and the other deviations which 
society had to control and eventually to repress. The implementa-tion of this fundamental distinction during the ﬁ  rst half of the 
19th century helped to give psychiatry its speciﬁ  c shape as a profes-
sion by being at the origin of forensic psychiatry and by leading to the formulation of precise rules concerning the commitment of the insane to institutions of a strictly medical character.
The legal code promulgated by Napoleon in 1810 stipulated that

The legal code promulgated by Napoleon in 1810 stipulated that 
‘no crime or delict exists if commited in a state of dementia’ , with the old term dementia being used as a synonym of Pinel’s mental alienation. This legal provision, introduced in similar forms in other countries, opened an important domain of activity to the medical profession of psychiatrist. Because of their now recognized specialized knowledge, the alienists were to help the judges in determining whether the mental state of an individual convicted of a ‘crime or delict’ was normal or pathological, with decisive conse-quences on the subsequent decision. The title of Esquirol’s Treatise
mentions explicitly that it describes mental diseases ‘in their medical, hygienic and medico-legal aspects’ . The conﬂ  ict (which still exists)

mentions explicitly that it describes mental diseases ‘in their medical, hygienic and medico-legal aspects’ . The conﬂ  ict (which still exists) 
between the judges, usually supported by public opinion, who took a restrictive view of the concept of mental disease; and the psychiatrists, who tended to expand it to include new types of devi-ant behaviour, is illustrated by the violent controversies provoked by Esquirol’s description of ‘homicidal monomania’ . They had an even more famous counterpart in England. J.C. Pritchard, an admirer of

19
Esquirol, had isolated ‘moral insanity’ as a speciﬁ  c mental disorder 
in two books published in 1837 and 1842; in the second, he exam-
ined its ‘relations to jurisprudence’ . Half a century later, in 1897, Henry Maudsley, who was in favour of the use of this diagnosis, recognized that this category, although internationally accepted by the psychiatrists, corresponded to
. . . a form of mental alienation which has so much the look of vice and crime that may persons regard it as an unfounded medical invention’ . Judges have repeatedly denounced it from the bench as a ‘most dan-gerous medical doctrine’ , ‘a dangerous innovation’ which, in the inter-est of society, should be reprobated.
The general acceptance of the new medical concept of mental

The general acceptance of the new medical concept of mental 
alienation implied the existence of adequate facilities for the treat-ment of the patients. The creation of new asylums—the term was retained—and the reorganization of the old ones were the answers. The French law of 1838 that ﬁ  xed the detailed rules for the expan-
sion of the new system to the whole country and for its functioning and ﬁ  nancial support had a model character. Similar results were 
obtained in, for example, England with the Asylum Act 1828 and the Lunacy Act 1845. Outwardly, the new system was the extension, under more humane conditions, of the previous institutional practices. However, it had radically original features. While recog-nizing the necessity of protecting society, it stressed the fact that the insane had a fundamental right to be protected and medically treated in a competent way. The deprivation of liberty for the 
patients which it still implied, was strictly controlled to prevent

patients which it still implied, was strictly controlled to prevent 
possible misuse and was anyway justiﬁ  ed, according to Esquirol 
and most contemporary psychiatrists, not only by the loss of free will, which was a consequence of the illness, but also by the thera-peutic value of separation from a pathogenic milieu.
The asylum system became the central element of psychiatric

care and was both the consequence and determining factor of the emergence of psychiatry as a medical specialty to which it gave, until the end of the 19th century and even beyond, an original character. The asylums acquired a quasi-monopoly in the care of the mentally ill. The few private institutions reserved for the wealthier members of the population, which often belonged to alienists in charge of the asylum, were generally submitted to the same legal rules. Private practice with ambulatory patients, as exist-ing today, was exceptional or dealt with cases which were not then considered to belong to mental alienation. As a result, the study of mental illness was predominantly restricted to the more severe forms of disorder. Another consequence was that the alienists in charge of patients committed to the asylums had a dual function, a fact that differentiated them from other hospital physicians. In addition to their medical duties, they were involved in legal procedures which

committed to the asylums had a dual function, a fact that differentiated them from other hospital physicians. In addition to their medical duties, they were involved in legal procedures which determined the conditions of admission, stay, and eventually release of the mentally ill. As superintendents, they also often had economic and ﬁ  nancial responsibilities, being in

charge of the material as well as the medical aspects of the func-
tioning of their institutions.
Despite the fact that the laws now strictly differentiated the nature 
of the limitations of liberty in asylums and in prisons, the participa-
tion of the alienist in a form of social control was eventually per-
ceived negatively by the public, and often by other physicians, and contributed to accentuating the speciﬁ  city of psychiatry inside 
medicine. During the third and the fourth decades of the 19th cen-tury, which saw the birth of the asylum system, the psychiatrists became really conscious of their identity as a professional group. In England, France, Germany, and the United States they founded 
societies and began to publish journals with specialized scientiﬁ  c 
goals. Such a description oversimpliﬁ  es an evolution which was

goals. Such a description oversimpliﬁ  es an evolution which was 
progressive and in some cases took different directions. The creation and the extension of the asylum system took many years; it did not reach its classical form until the last part of the century, as testiﬁ  ed 
by the famous campaign conducted in the United States during the 1840s by Dorothea Dix who complained that many of the mentally ill were still incarcerated in almshouses and prisons. The moral treatment practized in the institutions was eventually used to justify brutal measures, alleged to be therapeutic, and the behaviour of the attendants, who were not usually medically trained (signiﬁ  cantly, 
they were known as surveillants  in France), was too often of a purely 
repressive character. It was a long time before the proposals made in 1856 by the British psychiatrist John Conolly in his book, The

Treatment of the Insane without Mechanical Restraints  were put into 
practice everywhere.
The biological and the psychological model
The clinical orientation of Pinel, Esquirol, and their followers was basically empirical. By concentrating on describing observable symptoms and abnormal behaviours, it avoided theoretical controversies. However, many believed that if psychiatry was to become a branch of the medical sciences and to progress, it had to adopt models similar to those accepted by the rest of medicine. According to the anatomoclinical perspective, which was now dominant, diseases were distinct entities. Each disease was deﬁ  ned

by a characteristic pattern of symptoms provoked by a lesion or eventually, a dysfunction of an organ to be discovered at autopsy. In 1821, Bayle, following this scheme, described the typical clinical symptoms and lesions of the brain in the general paralysis of the insane. Despite the disappointing results of the further anatomo-pathological studies (brain lesions were observed in only a small proportion of cases), there was increasing conviction that, with 
better investigation methods, mental disorders, like other diseases, 
could be explained by somatic causes. The degeneration theory, proposed in 1857 by Morel, which attributed many forms of insan-ity to the hereditary transmission of dysfunction of the nervous system produced by the noxious effects of environmental factors, and whose inﬂ  uence lasted until Kraepelin, is another expression 
of this biological orientation whose aim was to give psychiatry an undisputed medical status.

The biological and the purely clinical approaches were concerned 
with different conceptual levels—the discovery of the causes of insanity and the description of its manifestations respectively. Therefore, they could easily coexist. Even when the followers of Pinel and Esquirol expressed reservations about the applicability of the biological model to every type of mental disorder, they still believed in the medical nature of psychiatry. The situation created in the German-speaking countries by the school of the ‘mentalists’ (the term Psychiker  by which they were known means ‘psychologi-
cally oriented’), who were predominant during the ﬁ  rst half of the 
19th century, was very different. Inﬂ  uenced by philosophical,

19th century, was very different. Inﬂ  uenced by philosophical, 
religious, and romantic trends, these psychiatrists took a radical dualistic position, postulating the absolute difference between the physical body and the spiritual soul. The soul was the source of the whole psychic life and hence eventually of its abnormal aspect—insanity. A term such as disease, appropriate for the somatic illness, 1.4 the history of psychiatry as a medical specialty

SECTION 1  the subject matter of and approach to psychiatry 20
could only be used metaphorically in psychiatry. The sins of the 
patients were the origin of the mental disorders, and psychiatry 
belonged more to moral philosophy than to medicine. These ideas were developed in various related forms by the majority of the German psychiatrists of the period (Heinroth, Ideler, Langerman, and many others). Their ideological position had two consequenc-es: scientiﬁ  c relations with other schools, such as the French and 
the English who saw in the publications of the mentalists obscure philosophical theories devoid of medical character, were largely cut off, and they provoked a violent reaction in Germany itself. The most extreme representatives of the contending group of ‘somatists’ ( Somatiker ), such as Jakobi and Friedreich, saw the

mental disorders as symptoms of somatic diseases, not necessarily of the brain. In fact for them mental diseases as such did not exist. They defended aggressively their biological and sometimes bizarre hypotheses, such as the aetiological role of intestinal worms, against the mentalists. Finally, around 1850, they gained the upper hand. The publication in 1845 of Pathology and Therapy of the Nervous 
Diseases  by Wilhelm Griesinger, an heir to their school who was 
also inﬂ  uenced by the French alienists, is a landmark in the history 
of the German psychiatry. With his appointment in 1865 as profes-sor of psychiatry in Berlin, where he succeeded the mentalist Ideler, medical psychiatry was deﬁ  nitely established in Germany as a 
branch of the natural sciences.
The rise of neuropsychiatry
Romberg’s Lehrbuch der Nervenkrankheiten  symbolizes the birth

Romberg’s Lehrbuch der Nervenkrankheiten  symbolizes the birth 
of neurology as an autonomous medical specialty studying and treating the diseases of the nervous system. It was published 5 years after Griesinger’s Textbook  in which, adopting and expanding 
Bayle’s anatomoclinical model he had afﬁ  rmed: ‘Mental diseases 
are diseases of the brain’ . If both psychiatric and neurological symptoms originated in the nervous system, some form of associa-tion between the two specialties was a logical step, at least at the conceptual level. One aspect of their complex relationship was the creation of neuropsychiatry which developed its most characteristic aspects in the German-speaking countries.
The universities acquired considerable power and inﬂ  uence in 
the second half of the 19th century. From the 1850s on, chairs were created for the teaching of the new common discipline and special

the second half of the 19th century. From the 1850s on, chairs were created for the teaching of the new common discipline and special 
institutions, the university clinics, were built with hospital beds 
for psychiatric patients (if their disorders became chronic they were sent to the nearest asylum), laboratories for research on neurophysiology and neuroanatomy, and special wards for the neurological cases were developed. Griesinger’s ﬁ  rst move when he 
took over the chair of psychiatry at Berlin was the creation of neurological wards at the Charité. The leading neuropsychiatrists in charge of these institutions often performed research in both ﬁ elds with equal competence, as shown by the work of Wernicke 
and Westphal, and later of Kleist and Bonhöffer, in Germany and of Meynert in Austria.
The concept of neuropsychiatry, appearing at a period during 
which the German school was progressively gaining inﬂ  uence, had

which the German school was progressively gaining inﬂ  uence, had 
a deep impact on psychiatric thought and on the psychiatric pro-
fession, even if its institutional driving force, the university clinic system, was not developed everywhere to the same extent as in Germany. For example, it was conspicuously absent in England, despite the fact that the theoretical position taken by the most important psychiatrist of the time, Henry Maudsley, was very close 
to that of Griesinger. The National Hospital in Queen’s Square, London, founded in 1860, retained a virtual monopoly on the teaching of neurology for many decades, and psychiatry, taught essentially in hospitals, was not represented at university level until the 1930s. However, in most countries, neuropsychiatric 
institutions coexisted with the asylums where the alienists had

institutions coexisted with the asylums where the alienists had 
the unenviable task of caring for chronic mental patients, often with inadequate means. The concept of neuropsychiatry reﬂ  ected a 
basically biological perspective on the aetiology of the mental ill-nesses, expressed in the creation of a new specialty associating competence in the two previously separated domains of medicine. However, it provoked ideological and professional tension between the ‘pure’ psychiatrists, mainly those in charge of asylums, and the neuropsychiatrists, predominantly involved in teaching and research. In the long term, this conﬂ  ict was one of the factors which 
ﬁ nally led, in the 1960s, to the almost complete administrative and 
institutional separation of the two specialties in countries such as France where they had been, at least formally, associated. But many traces of the old situation remain. The most inﬂ  uential scientiﬁ  c

journal published in German, Nervenarzt , still deals equally with 
neurology and psychiatry, and the term ‘neuropsychiatric’ survives in the titles of many teaching and research institutions.
The neuroses and the birth of the 
psychotherapies
The study of the neuroses, in which the relation between psychiatry 
and neurology was also involved, resulted in completely different, but equally important changes to psychiatry as a medical specialty. The term neurosis had been coined in 1769 by Cullen to describe a class of diseases he attributed to a dysfunction of the nervous system. In this very heterogenous group, two entities of very ancient origin, hysteria and hypochondriasis, had predominantly psycho-logical manifestations. Since the affected patients were not usually commited to asylums, they were not normally studied by alienists, but by specialists in internal medicine such as Briquet, who in 1859, wrote the classical Treatise on Hysteria . Because of the assumed

nature of the neuroses, the new discipline of neurology rapidly took an interest in them.
Charcot, the founder of the French neurological school, was 
responsible for the internal medicine wards at the Salpêtrière—they 
were not associated with the ‘divisions of the insane’ at the same hospital, the domain of the alienists. In about 1880, he became interested in hysterical patients who, because of their seizures, were admitted to the same ward as the epileptics. He developed a purely neurological theory of the disease which he described and studied using hypnosis. This was the former ‘animal magnetism’ , long fallen into disrepute, but to which he gave a new scientiﬁ  c status. 
Charcot’s descriptions of the grande hystérie , which he demonstrated

Charcot’s descriptions of the grande hystérie , which he demonstrated 
on selected patients in his famous public lectures, were justly criti-cized later, but his international fame attracted students from all over the world. One of them, was a young lecturer in neuropathol-ogy at the University of Vienna, Sigmund Freud, who, impressed by Charcot’s lectures, decided to devote all his energies to the study and the treatment of the neuroses. Another was a French professor of philosophy (psychology was then a branch of philosophy), Pierre Janet, who had become interested in the psychological aspects of the neuroses. He was later to develop, in parallel with Freud, a

21
psychopathological theory which, despite the traces it has left (the 
concepts of psychasthenia and the dissociative processes in hyste-
ria) was not to be as internationally successful as Freud’s psychoa-nalysis. Charcot’s ideas were opposed by Bernheim, the professor of internal medicine at the Nancy Medical School and also an adept of hypnosis. He attacked the neurological interpretations of the Salpêtrière and claimed that suggestion played a central role in the phenomena described by Charcot.
The general interest in the neuroses, which extended beyond 
medicine to ﬁ n de siècle  literature, was an international phenome-
non. In 1880, Beard, an American neurologist, described a new neurosis, neurasthenia, which soon aroused even more interest than Charcot’s hysteria. Psychiatry had played almost no part in this evolution, but this was to change under the inﬂ  uence of three

related developments: the changes which took place within the concept of neurosis, the birth of the psychotherapies, and the incorporation in the ﬁ  eld of psychiatry of psychopathological 
manifestations, even if they were of minor intensity.
The transformation of the concept of neurosis is apparent in the 
position taken by Kraepelin in the 1904 edition of his Textbook . He 
introduced a chapter,‘The psychogenic neuroses’ , on the grounds that ‘among the neuroses, to which belong epilepsy and chorea, one must isolate a sub-group characterized by the purely psychological cause of the apparition of the symptoms’ . The disintegration of the old concept left to neurology, which from now on abandoned the generic term, diseases (such as epilepsy and chorea) whose somatic manifestations could be shown to express a dysfunction of a precise part of the nervous system. Psychiatry took charge of hysteria, 
hypochondriasis, neurasthenia, and the related phobic, obsessional,

hypochondriasis, neurasthenia, and the related phobic, obsessional, 
and anxious disorders, which constituted the new neuroses. This concept was justiﬁ  ed by the psychological nature of the symptoms 
and the causes recognized even by a biologically oriented psychia-trist such as Kraepelin. This redrawing of the frontier between the neurological and psychiatric specialties also testiﬁ  ed to the 
extension of the limits of psychiatry. Pinel’s insanity, until then deﬁ ned by the necessity of commitment to special institutions, 
was replaced by a broader concept. A new class corresponding to our present personality disorders had already appeared in the 1894 edition of Kraepelin’s Textbook . It had been isolated for the ﬁ  rst 
time in 1872–1874 by the psychiatrist Koch. Like the neuroses, the cases were rarely observed in asylums but, nevertheless, they were now considered as belonging to the psychiatric ﬁ  eld of study.

This ﬁ  eld was further modiﬁ  ed by the birth of the psychothera pies. 
In fact, they had a long history. In 1803, one of the ﬁ  rst German 
mentalists, Reil, had described under the name of ‘psychic therapy’ (psychische Curmethode ) a number of procedures, including 
very violent somatic ones, which could inﬂ  uence the ‘perturbed 
passions of the soul’ , and Pinel’s moral therapy contained psycho-therapeutic elements. However, psychotherapies as techniques whose formal rules were based on an explicit theory about their 
psychological mechanisms of action, derived mainly from Mesmer’s 
animal magnetism as rehabilitated by Charcot. The emergence of the psychotherapies, characteristic of the last decades of the 
19th century, was intimately related to the renewed study of the

19th century, was intimately related to the renewed study of the 
neuroses. After he had abandoned hypnosis, Freud developed psychoanalysis, but many other techniques evolved during the 
same period, which were as well or even better known at the time, 
although they were to have a less lasting success. One of these was the method of Janet, who still occasionally used hypnosis. In 1904, Dubois, a Swiss neuropathologist from Bern, introduced a 
technique inﬂ  uenced by Bernheim’s theory of suggestion in The 
Psychoneuroses and their Moral Treatment , and claimed to produce 
a ‘psychological re-education’ by a combination of rational and

a ‘psychological re-education’ by a combination of rational and 
persuasive elements. His international reputation brought him patients from all over the world. The ‘rest cure’ , proposed in 1877 by the American neurologist S. Weir Mitchell for the treatment of hysteria and later of neurasthenia, was combined with Dubois’ method by Dejerine, Charcot’s successor as the professor of neurol-ogy in Paris.
This very incomplete summary illustrates the striking fact that,

This very incomplete summary illustrates the striking fact that, 
because of their intimate connections with the neuroses, the psychotherapies originated inside neurology. When the study and treatment of the neuroses were incorporated into psychiatry, the psychiatrists considered that they were an integral part of their activity and tried to retain the monopoly of their practice. They never completely succeeded. Already Freud had, according to his biographer Jones, ‘warmly welcomed the incursion in the thera-peutic ﬁ  eld of suitable people from another walk of life than 
medicine’ . The problem of the ‘lay analysts’ , a source of conﬂ  ict 
within the psychoanalytic movement, is only an aspect of a broader question which was later to involve the relations of the medical specialty of psychiatry with the new professional group of clinical psychologists.
From the beginning of the 20th century to 
the Second World War
During the ﬁ  rst half of the 20th century, psychiatry developed in

During the ﬁ  rst half of the 20th century, psychiatry developed in 
many directions. Kraepelin’s monumental synthesis(5) established 
around 1900, a nosological system which, in its broad outlines, has remained valid until today. Without being radically altered it was completed, to mention only a few contributions, in 1911, by Bleuler’s description of schizophrenia and in 1913, by Jaspers’ psychopathological perspective, developed by the Heidelberg school and Kurt Schneider, and by other psychiatrists working in academic institutions. However, the old conﬂ  ict between the 
‘mentalists’ and the ‘somatists’ reappeared in a modiﬁ  ed form. The 
mainstream of psychiatry had abandoned the extreme positions of the ‘brain pathologists’ of the Meynert-Wernicke type but, while recognizing a limited inﬂ  uence of psychological factors, admitted

mainstream of psychiatry had abandoned the extreme positions of the ‘brain pathologists’ of the Meynert-Wernicke type but, while recognizing a limited inﬂ  uence of psychological factors, admitted 
in a general way the biological origin of the more severe mental disorders—the psychoses. The empirical discoveries of biological 
treatments—of general paralysis by malaria therapy (Wagner von

Jauregg in 1917), of schizophrenia by insulin coma (Sakel in 1933) or by chemically induced seizures (von Meduna in 1935), and of depression by electroconvulsive therapy (Cerletti in 1938)—not only helped to dispel the prevailing therapeutic pessimism, but provided supporting arguments. However, an opposing ideological current represented by psychoanalysis had arisen from the study of the neuroses. Its attention was concentrated on the study of com-plex psychopathological mechanisms postulated to be at the origin of the neurotic, and later also of the psychotic symptoms, favoured psychogenetic aetiological theories, and advocated psychotherapy as the fundamental form of treatment. Psychoanalysis expanded steadily during this period and gained enthusiastic adherents in many countries. However, partly because of the suspicion and even hostility of many members of the psychiatric establishment, they remained isolated in close-knit groups with their own teaching 1.4 the history of

However, partly because of the suspicion and even hostility of many members of the psychiatric establishment, they remained isolated in close-knit groups with their own teaching 1.4 the history of psychiatry as a medical specialty

SECTION 1  the subject matter of and approach to psychiatry 22
system independent of the ofﬁ  cial medical curriculum, and the use 
of their therapeutic technique was restricted to a small number of mostly neurotic patients seen in outpatient clinics or, more often, in private practice.
The great majority of patients suffering from mental disorders 
were still conﬁ  ned in asylums, and the enormous increase in their 
number, mainly related to the social changes accompanying indus-trialization and urbanization, although other factors have been invoked, was striking. In Great Britain it grew from 16 000 in 1860 to 98 000 in 1910, three times more rapidly than the population. A similar phenomenon was observed in all countries and persisted until the end of the 1940s despite the introduction of the ﬁ  rst

biological therapies. In the United States, there were already 188 000 patients in mental hospitals in 1910, and by the end of the Second World War, 850 000 were lodged in huge institutions which were overpopulated, understaffed, and could only provide custodial care. This obvious degeneracy of the asylum system, contrasting with the progresses in the scientiﬁ  c ﬁ eld, stimulated efforts to improve 
the practice of psychiatry and its institutional framework. Most of these improvements took place after 1920 and, although their results remained relatively limited, they were the forerunners of later more drastic changes.
The education of psychiatric specialists, which had varied widely

The education of psychiatric specialists, which had varied widely 
from country to country, was improved and systematized. A con-vergence of evolution is apparent during this period which can be said, to some extent, to have seen the formal administrative recog-nition of psychiatry as a medical specialty. Educational programmes and controls of the level of competence were introduced which extended beyond psychiatrists in academic positions. A limited teaching of psychiatry became compulsory even in the general medical curriculum. In France, psychiatrists for public asylums and, in some cases, residents in psychiatry were selected by a competitive examination system. In England, the Board of Control recommended in 1918, that a leading position in a psychiatric insti-tution could only be occupied by a physician who had obtained a Diploma in Psychological Medicine awarded by the Royal College of Physicians and by ﬁ  ve universities. In the United States, the

moving force behind the reforms was Adolf Meyer, the Director of the Henry Phipps Clinic at Johns Hopkins University from 1913 to 1939, who organized a systematic residency system and promot-ed the creation of the Board of Neurology and Psychiatry. This Board was established in 1936 and awarded a diploma which it became necessary to hold, to be recognized as a specialist.
The changes were reﬂ  ected in the vocabulary. The term psychia-
try, originating in the German-speaking countries and mostly used there, was adopted everywhere at the beginning of the century. In France, the health authorities ofﬁ  cially substituted ‘ hôpital psychi-
atrique ’ for ‘ asile d’aliénés ’ and ‘ psychiatre ’ for ‘ aliéniste ’ in the 1930s. 
In England, a Royal Commission used the words ‘hospital’ , ‘nurse’ , and ‘patient’ instead of ‘asylum’ , ‘attendant’ , and ‘lunatic’ for the ﬁ  rst

In England, a Royal Commission used the words ‘hospital’ , ‘nurse’ , and ‘patient’ instead of ‘asylum’ , ‘attendant’ , and ‘lunatic’ for the ﬁ  rst 
time between 1924 and 1926. However, efforts were also made to dissociate, when possible, the social protection function of the insti-tutions from their medical role by allowing them to admit patients under the same conditions as the general hospitals. In 1923, a special section was created in the Paris Sainte-Anne asylum which provided 
treatment to voluntary patients and had both hospital beds and a 
large outpatient department. In England, the Mental Health Act of 1930 made voluntary admissions to psychiatric hospitals possible; by 1938, they already constituted 35 per cent of all admissions.Social considerations had always been evident in psychiatry, but 
their traditional expressions had mainly been of a negative nature, i.e., the conﬁ  nement of patients in asylums. The new possibility of

their traditional expressions had mainly been of a negative nature, i.e., the conﬁ  nement of patients in asylums. The new possibility of 
free admissions reﬂ  ected an increase in tolerance towards the dis-
turbing character of mental illness. At the same time, a differently oriented and broader social perspective appeared. The concept of mental hygiene originated in the United States in 1919 with the creation by a former patient, Clifford Beers, of an organization whose internationally growing inﬂ  uence was manifested by well-
attended congresses held in Washington in 1930 and in Paris in 1937. From its beginning, the movement was not purely medical and was inﬂ  uenced by various humanitarian philosophical trends.

attended congresses held in Washington in 1930 and in Paris in 1937. From its beginning, the movement was not purely medical and was inﬂ  uenced by various humanitarian philosophical trends. 
It emphasized the role of social factors, such as living conditions or educational practices, in the origin of mental disturbances and promoted their prevention and treatment by the close co-operation of psychiatrists and nurses with non-medical groups in the community. One of the institutional consequences of these ideas was the creation of the profession of social worker. They began their activity in Adolf Meyer’s clinic (Adolf Meyer had been an early supporter of the mental hygiene movement whose princi-ples converged with his own ideas) at the Sainte-Anne Hospital in Paris, in England where the London School of Economics opened a special training course in 1929, and elsewhere.
Contemporary with the emergence of psychiatric social work

Contemporary with the emergence of psychiatric social work 
was the expansion of clinical psychology. The Binet-Simon scale for the measurement of intelligence, developed in 1905, was the ﬁ rst application to psychiatry of the new discipline of experimental 
psychology which had originated at the end of the previous century.This initial contribution led to the creation of a professional class of clinical psychologists who were initially concerned with the development and use of psychological assessment instruments and with theoretical research in a few psychiatric centres. Their number initially remained low; in 1945 the United States, where they were most numerous, had about 4 000 psychiatrists but only 200 clinical psychologists.
The expansion of psychiatry after 1945

The Second World War coincided with a major transformation of the psychiatric specialty. The war had vividly demonstrated the frequency of mental disorders in the United States; they had proved to be the leading cause of medical discharges from the military ser-vice and the primary cause of almost 40 per cent of selective service rejections. The previously prevailing view that psychiatry was a minor and often somewhat despised medical discipline, concerned primarily with the custodial care of psychologically deviant and potentially troublesome individuals, was progressively dispelled. The preservation and the restoration of mental health—an expression from now on often used by national and interna-tional institutions—began to be considered by governments as an important task. The fundamental changes which took place after 1945 and shaped psychiatry as we know it today were the result of

this new atmosphere and of the emergence of new perspectives in 
the three traditional domains— the psychological, the social, and the biological. Some appeared in slightly different forms at different 
times, their relative inﬂ  uence was submitted to variations, and 
eventually they came into conﬂ  ict. The result has been an impressive 
expansion and increase of the efﬁ  cacy of psychiatry, profound 
institutional transformations, and successive ideological waves

23
which have had a major impact on the professional position of the 
psychiatrist.
The demographic data reﬂ  ect the new importance of psychiatry 
in medicine. In the United States, the proportion of psychiatrists in the medical profession was 0.7 per cent in 1920, 1.4 per cent in 1940, and 5.5 per cent in 1970, the rate of growth having doubled after the Second World War. In France, at present there are 18 psychiatrists for 100 000 habitants; they constitute 6 per cent of all physicians. Similar levels were reached during the postwar dec-ades in the developed countries and remain relatively stable today. Even before this spectacular increase in numbers, psychiatrists had been becoming conscious of the necessity to afﬁ  rm the identity of

their discipline. The First World Congress of Psychiatry, held in Paris in 1950, has been followed by periodic meetings and by the creation of the World Psychiatric Association to which almost every national society of psychiatry belongs. The health authorities of various countries have become conscious of the necessity to provide adequate ﬁ  nancial means to support research and training 
in the discipline. In 1946, the United States government created the National Institutes of Mental Health for such a purpose, and simi-lar efforts were made in many countries although the structures of the organizations formed were different. T o promote the same goals at the international level, the World Health Organization, created immediately after the Second World War, had a Section (later Division) of Mental Health which, among other co-ordinating
activities, tried to overcome the difﬁ  culties of communication 
between the national schools by establishing a common nosologi-cal language.

While the changes affected almost all countries, they were most 
spectacular in the United States. From the end of the 19th century until the 1930s, the concepts developed in the German-speaking countries had been the most inﬂ  uential. This disappeared with the 
advent of the National Socialist regime which, under cover of racist theories, expelled many of the leading psychiatrists from Germany and Austria, introduced compulsory sterilization for several variet-ies of mental illnesses, and promoted the voluntary killing in psychiatric hospitals of mentally-retarded children and chronic patients. The United States, which had emerged from the Second World War as the most powerful country in the world, began to exert a widespread inﬂ  uence in psychiatry as in the rest of medicine.

Because of the prestige of its research and teaching institutions and the worldwide inﬂ  uence of its scientiﬁ  c publications, reinforced by 
the progressive adoption of English as the language of international scientiﬁ  c communication, American psychiatry became a model in 
many countries, even though many of the theoretical trends and technical advances it adopted and developed had originated in Europe. However, in the United States, with a local colouring, they took on a special intensity.
The psychodynamic wave

An important factor in the spread of the doctrine of psychoanalysis was the emigration of a relatively large number of German and Austrian psychoanalysts to the United States from 1933 onwards. They had been compelled to leave their home countries for racial reasons—psychoanalysis had been condemned by the National Socialist regime as Jewish and Freud’s books had been publicly burned. Many of the young psychiatrists trained in large numbers to answer the demands of the armed forces adopted psychoanalysis under the inﬂ  uence of some of those in charge of the programmes. For a generation, until the end of the 1960s, psychoanalysis became 
the dominant ideology in American psychiatry.
The American form of psychodynamism often deviated from

The American form of psychodynamism often deviated from 
Freudian orthodoxy, but it emphasized the role of psychogenetic factors, the value of the study of intrapsychic mechanisms, and the basic importance of psychotherapy, while giving little consider-ation to the traditional clinical approach and to nosology. The domination of this essentially psychological orientation, some-times compared with the success of the German mentalist school during the ﬁ  rst half of the 19th century, had important conse-
quences. Although the disorders of hospitalized psychotics were eventually interpreted according to psychoanalytic theory, psycho-
therapy was mostly used, as it has been since its beginning, on 
ambulatory neurotic patients. As early as 1951–1952, 3 000 of the 7 500 American psychiatrists identiﬁ  ed private practice as their

ambulatory neurotic patients. As early as 1951–1952, 3 000 of the 7 500 American psychiatrists identiﬁ  ed private practice as their 
main activity, and in 1954, the number of private psychiatrists exceeded that of their salaried colleagues for the ﬁ  rst time, with 
a quarter of the former devoted exclusively to psychotherapy. However, with the initial encouragement of ofﬁ  cial institutions 
such as the Veterans Administration, the clinical psychologists began to engage in psychotherapeutic activities. The number of members of the Clinical Psychology Section of the American Psychological Association reached 20 000 in 1980, at a time when they were 26 000 psychiatrists in the United States. In public opinion, and to a certain extent in general medical opinion also, psychiatry was assumed to consist only of psychotherapy and psychology.
In most other countries the developments that occurred in the

In most other countries the developments that occurred in the 
United States were not as intense, generally appeared later, and were modiﬁ  ed by local traditions and inﬂ  uences. In the German-
speaking countries they were delayed by the still powerful neuro-psychiatric perspective and the temporary vogue for existential phenomenology. In the United Kingdom, the eclectic current fos-tered by the inﬂ  uential London Institute of Psychiatry during the 
decades following the war restricted the advance of psychodyna-mism; in 1956, Time Magazine  could afﬁ  rm, as a conclusion of 
a survey, that ‘all of Great Britain [had] half as many analysts as New Y ork City’ . In France, the psychoanalyst Jacques Lacan gave the doctrine a special colouring. On the whole, however, the rise of psychodynamism was a general phenomenon, except in the 
communist countries where Freud’s doctrine had been condemned on ideological grounds.
A reaction began in the 1960s with the successes of the new phar-

macotherapies. Clinical psychologists had developed alternative radically different psychotherapeutic methods based on learning theories, especially the behaviour therapy introduced in 1958 by Wolpe, supported in the United Kingdom by Eysenck, and the cog-nitive therapy often associated with it. These methods competed successfully with the psychodynamic techniques and conquered a large part of the ﬁ  eld. Psychodynamism did not disappear; many of 
its concepts retained their place in psychiatry and psychotherapeu-
tic methods continued to be practized, but it lost its predominant 
ideological position. In addition to its theoretical contributions, when its inﬂ  uence on the professional aspect of psychiatry is con-

sidered from a historical perspective, it has been an important factor in the further expansion of the activity of psychiatrists in the treatment of relatively minor disorders and has also encour-aged clinical psychologists to play an active and independent role in this ﬁ  eld.1.4 the history of psychiatry as a medical specialty

SECTION 1  the subject matter of and approach to psychiatry 24
The social wave
At the end of the Second World War there was a great desire for 
social change; one of its aspects was the belief that everyone had a ‘right to health’ or at least the right to receive adequate medical care regardless of the ability to pay. This resulted in the creation of the National Health Service in the United Kingdom in 1948 and the Social Security system in France, together with similar develop-ments in other countries. The social perspective, which was one of the basic principles underlying these developments, initiated major institutional changes in psychiatry. They were the result of a number of factors—the necessity to give to the whole population an easy access to psychiatric care, and also the belief that social elements played an important role in the aetiology of the mental

disorders and that they could greatly contribute to the healing pro-cess, with the aim of progressively reintegrating the patient in the 
community.
The most spectacular aspect of the new policy was the decline of

the asylum system, still in a dominant position in psychiatry; in fact, the number of patients in psychiatric hospitals in the devel-oped countries reached its peak in 1955. The criticisms of the ‘degeneration’ of the functioning of psychiatric hospitals and the segregation of patients in institutions, often located far from their homes and families, were not new. However, the previous partial improvements, such as the decrease in the number of compulsory commitments or the creation of outpatient departments, were replaced by the creation of completely new structures. Ideally, the country would be divided into geographical zones or sectors with a population of about 100 000, and each zone would have a multidis-ciplinary team of psychiatrists, nurses, clinical psychologists, social workers, and occupational therapists responsible for mental health. Visits and therapeutic interventions in the patient’s home and eas-ily accessible outpatient departments were to play an increasingly

and occupational therapists responsible for mental health. Visits and therapeutic interventions in the patient’s home and eas-ily accessible outpatient departments were to play an increasingly important role. If hospitalization was necessary, it should be as far as possible in small units located in a general hospital where the time of stay was to be reduced to the absolute minimum. Special institutions such as day hospitals, night hospitals, and specially adapted workshops would contribute to the progressive readapta-tion of the patient to the life in the community. The introduction of this ‘community care’ , which was expected to work in close co-operation with general practitioners and various public and

private institutions, would result in the disappearance of the tradi-
tional psychiatric hospital and to ‘deinstitutionalize’ psychiatry. The new system was introduced in various forms in most countries after 1969. In the United States, the Community Mental Health Center Act was promulgated in 1967. In the United Kingdom, which had strong traditions of social psychiatry, plans for the implementation of community care were discussed in the 1960s, and in 1975, the Government White Paper Better Services for the 
Mentally Ill  encouraged the formation of multidisciplinary ‘primary 
care teams’ which also included general practitioners. In France, an ofﬁ cial directive in 1960 created the psychiatrie de secteur  which 
was expected to result in the progressive elimination of hospitalo-
centrisme . The World Health Organization (WHO) encouraged all 
its member countries to adopt similar practices.
Although, in the last 40 years community care has become the

Although, in the last 40 years community care has become the 
ofﬁ cial doctrine everywhere, except in Japan where the rate of hos-
pitalization in mostly private hospitals has grown continuously, its implementation has not been easy despite the major therapeutic improvements brought about by pharmacotherapy. In some parts of the United States, the sudden closure of public psychiatric hos-
pitals combined with the inadequacies of the Community Mental Health Centers were for a time at the origin of an appalling lack of care for a number of mentally ill people. The expected ‘fading out’ of hospitalization has been slow. According to the WHO, in 1976 the number of mental health beds (including beds for the mentally retarded) per 1 000 population was 6.5 in Sweden, 5.5 in the United Kingdom, 3 in France, and 2 in Germany. These ﬁ  gures have since

decreased and the types of hospitalization have changed. In 1955, 77 per cent of the ‘psychiatric care episodes’ in the United States occurred in public psychiatric hospitals, compared with 20 per cent in 1990. In 1994, 1.4 million mental patients were hospitalized, but only 35 per cent in public psychiatric hospitals compared with 43 per cent in general hospitals and 11 per cent in private psychiat-ric hospitals, which increased in number from 150 in 1970 to 444 in 1988. In France, where the total number of psychiatric patients treated in public institutions (including children) is now about a million, 60 per cent are seen exclusively on an ambulatory basis, but the number of hospital beds has only been reduced by half.
Reﬂ ecting the increasing inﬂ  uence of social perspectives, the 
organizational changes modiﬁ  ed psychiatry as a profession. The

organizational changes modiﬁ  ed psychiatry as a profession. The 
increase in the number of psychiatrists in private practice was paralleled, in general to a lesser extent, by an increase in the public sector where their role was modiﬁ  ed. In the traditional asylum, the

authority of the psychiatrist was unchallenged and limited only by the legal provisions related to the procedures of commitment. The nurses, and later the clinical psychologists, social workers, and occupational therapists, were ‘paramedical auxiliaries’ in a subordi-nate position. The creation of multidisciplinary teams, working in various settings, gave the psychiatrist a function of co-ordination made increasingly complex by the claims of professional autonomy made by the former auxiliaries. In some cases, such as in the American Mental Health Centers, the psychiatrists who were a small minority in the team and had less and less control over its functioning, resented what they considered to be the loss of their medical status.
The importance given to social factors was not limited to the 
system by which care was delivered. Sometimes, combined with radical ideological and political attitudes, it took more extreme forms. The criticisms, which ﬁ  rst centred on the inadequacies of

system by which care was delivered. Sometimes, combined with radical ideological and political attitudes, it took more extreme forms. The criticisms, which ﬁ  rst centred on the inadequacies of 
the existing institutions, extended to the concept of mental disease itself. The antipsychiatric movement claimed that mental diseases were artiﬁ  cial constructs which were not related to diseases in the 
medical meaning of the term. The allegedly pathological behav-iours, such as those conceptualized as schizophrenia, were in fact normal reactions to an inadequate social system. The so-called 
treatments were techniques used by the ruling classes to preserve 
the social order of which they were the beneﬁ  ciaries. The only

the social order of which they were the beneﬁ  ciaries. The only 
solution was a drastic reform of society. Such theses varied in their content and in the arguments used. They were developed by authors such as Szasz, Laing, and Cooper in the English-speaking world, the philosopher Foucault in France, and the psychiatrist Basaglia in Italy. They reached their greatest inﬂ  uence in the 1960s and a 
few attempts were made to put their ideological principles into 
practice. Although they attracted much attention at the time, they were very limited and short lived. One of the few countries where this movement had a practical impact was Italy. Basaglia’s strongly politically oriented theories were inﬂ  uential in the later legal reform 
of the antiquated asylum system, but, despite the apparently

25
revolutionary character of some of the new administrative provi-
sions, the changes made were very similar to those taking place in other countries.
The biological wave
Psychotropic drugs, such as opium, had been used since the origin of the medical treatment of psychiatric patients. During the 19th and the ﬁ  rst half of the 20th century, synthetic drugs such as the

bromides, the barbiturates, and the amphetamines were developed. Some of them, especially the sedatives and hypnotics, had a real but in practice, marginal value in alleviating some symptoms. They had never constituted an effective treatment of mental disorders. Modern psychopharmacology not only initiated what has been rightly called a therapeutic revolution in psychiatry but also gave a powerful new impulse to the biological perspective. Its date of birth is usually considered to be 1952, when the remarkable activity of chlorpromazine on the symptoms of schizophrenia and mania was discovered. This had been preceded in 1949 by the demonstra-tion of the value of lithium salts in manic states. A few years later, it was shown that the continuous administration of lithium salts prevented the recurrence of manic and depressive phases in the mood disorders. This was followed by the introduction of drugs acting on the depressive manifestations (imipramine and the monoamine oxidase

the recurrence of manic and depressive phases in the mood disorders. This was followed by the introduction of drugs acting on the depressive manifestations (imipramine and the monoamine oxidase inhibitors in 1957) and on anxiety (including chlorediazepoxide, the prototype of the benzodiazepines, in 1960). In one decade, clinicians had empirically discovered the ﬁ  elds

of application of the main classes of psychoactive drugs—the neuroleptics, the antidepressants, the anxiolytics, and the mood stabilizers—which had been synthesized by biochemists and previ-ously tested by pharmacologists on animal models. The scale and rapidity of the spread of their use had major repercussions.
The ﬁ  rst was a modiﬁ  cation of the image of psychiatry. The lay-
man generally expected a physician to prescribe drugs to treat the disease from which he suffered. In part, because it did not conform to the expected therapeutic behaviour, psychiatry had been seen as an atypical and almost non-medical specialty. In addition to the speciﬁ  city of the institutions in which it was generally practized,

psychological techniques were unknown in the rest of medicine, and even the recently introduced biological techniques (the shock therapies and the lobotomy) had a somewhat strange and frighten-ing character. The establishment of pharmacotherapy contributed strongly to modifying this perception, even if it did not completely remove the traditional prejudices.
The second consequence was even more important. There were, 
at least initially, controversies about the roles of pharmacotherapy and of the new social perspectives in the restructuring of the 
mental health care system. In fact, the number of inpatients in 
psychiatric hospitals began to decrease from 1955 on, and it seems obvious that the main cause was the therapeutic efﬁ  cacy of the 
drugs. They reduced the mean length of hospitalization and even-tually even made it unnecessary. Although some types of patients did not beneﬁ  t from them and the mental state of others was only

drugs. They reduced the mean length of hospitalization and even-tually even made it unnecessary. Although some types of patients did not beneﬁ  t from them and the mental state of others was only 
improved, many who had previously been condemned to long stays in the hospital were able to return to the community, with their treatment eventually being continued in rehabilitation settings and often on an ambulatory basis. Pharmacotherapy had made possible the practical implementation of social trends. In addition to this basic contribution to the ‘deinstitutionalization’ movement, pharmacotherapy was an essential factor in the growth of private practice. The success of psychotherapy had been one contribution

to this, but the complexity of its techniques, the length of the treat-ment, its applicability to only a few types of disorders, and the uncertainty of the results limited its use to a relatively small num-ber of selected patients, even in the United States during the period of the greatest popularity of psychodynamism. Pharmacotherapy 
could be used much more easily, on a much larger number of 
patients, and did not require a long and complex training. Some of the drugs, such as the anxiolytics, had an immediate sympto-matic effect, and others (the antidepressants and the neuroleptics) could attenuate or suppress the pathological manifestations in a few weeks and, outside the acute phase requiring hospitalization, could be used on an ambulatory basis. It was not only private psychiatrists who were able to treat many of their patients success-fully; general practitioners also began to prescribe psychotropic drugs on a large scale.

The third consequence was the explosive development of bio-
logical research in psychiatry. The ﬁ  rst therapeutic discoveries were 
largely empirical, but new biochemical techniques allowed some of the modes of action of the drugs to be elucidated. From 1960 on, studies of the inﬂ  uence of these drugs on various aspects of neuro-
transmission in the brain stimulated hypotheses about the abnor-mal biochemical mechanisms considered to be the physical sub-strate of the mental disorders. Meanwhile new methods had been introduced for examination of morphological modiﬁ  cations of the

living brain and even of the nature and localization of the bio-chemical processes taking place in its different parts. The discovery by Watson and Crick in 1953, of the chemical basis of heredity and the subsequent spectacular advances in molecular biology gave a fresh impulse to psychiatric genetics, which had been partly dis-credited by their misuse by the National Socialist regime. Under the name of neurosciences, these new ﬁ  elds of enquiry progressively 
acquired a dominant role in psychiatric research at the same time as the introduction of an ever-increasing number of drugs, eventu-ally more potent, usually with less inconvenient side-effects, and sometimes with new therapeutic indications.
‘Remedicalization’ of psychiatry
In 1983, Melvin Sabshin, the Director of the American Psychiatric Association, summarized the overlapping chronologies of the psychodynamic, biological, and social waves as follows:
(6)

(6)
Psychoanalysis surged through the United States during the 1940s and the 1950s. During the 1950s, a new psychopharmacological approach emerged which had great impact on psychiatric practice generally . . . The 1960s saw the dawning of a community psychiatric approach which attempted to accomplish a massive desinstitutionalization of patients from public psychiatric hospitals.
Although less radical and not strictly identical, the general picture 
was similar in other countries. The 1960s saw an often uneasy coexistence of three schools. ‘During that decade’ , wrote Sabshin, ‘American psychiatry enlarged its boundaries and its practices so broadly that many critics grew increasingly concerned with the ‘bottomless pit’ of the ﬁ  eld’ . The extension of the practice of

psychotherapy, frequently to cases with no clear pathological character, tended to blur the limits of the mental disease concept and to neglect the traditional diagnostic approach. Social work was also tempted to concern itself with problems with no obvious med-ical nature, such as those still described in 1978 in the United States by the President’s Commission of Mental Health, which asserted 1.4 the history of psychiatry as a medical specialty

SECTION 1  the subject matter of and approach to psychiatry 26
that ‘American mental health cannot be deﬁ  ned only in terms of 
disabling mental illness and identiﬁ  ed mental disorders’ and identi-
ﬁ ed as a domain of concern for workers in the ﬁ  eld ‘unrelenting 
poverty and unemployment and the institutionalized discrimina-tion that occurs on the basis of race, sex, class, age . . .’ . In sharp contrast, the new biological psychiatry recognized only a strictly medical model, stressing the necessity of an accurate diagnosis for the prescription of the drugs and for the testing of their efﬁ  cacy, and 
advocated restrictive limits in the deﬁ  nition of the mental diseases.
Around 1970, a profound change took place. Although the insti-
tutional modiﬁ  cations of the care system favoured by the general-
ization of drug therapy continued and expanded under its various forms everywhere, the inﬂ  uence of psychodynamism began to

ization of drug therapy continued and expanded under its various forms everywhere, the inﬂ  uence of psychodynamism began to 
decline within the psychiatric profession. According to the Director of the National Institutes for Mental Health ‘it was nearly impossible in 1945 for a non-psychoanalyst to become Chairman of a Department of Psychiatry (in the United States)’ but by the mid-1970s the situation was reversed. The publication by the American Psychiatric Association of the Third Revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) is often consid-ered as the symbolic expression of the change. This took place in 1980, but its origins were more than a decade previously, and it was signiﬁ  cantly presented by its apologists, such as Klerman, as 
‘a decisive turning point in the history of American psychiatry . . . an afﬁ  rmation of its medical identity’ . The new nosology, which

‘a decisive turning point in the history of American psychiatry . . . an afﬁ  rmation of its medical identity’ . The new nosology, which 
was categorical in nature and which introduced diagnostic criteria borrowed from experimental psychology in the delimitation of the categories, did not allow any reference to ‘unproven’ aetiological factors or pathogenic mechanisms, unless ‘scientiﬁ  cally demon-
strated’ . It claimed to be purely descriptive and therefore acceptable as a means of communication by all psychiatrists, whatever their individual orientation may be. It was in fact perceived, not only in its country of origin, as a reaction against the extreme socio-psychological positions—the deletion of the term neurosis because of its usual association with the psychoanalytic theory of intra-psychic conﬂ  icts raised violent controversies—and, despite its

proclaimed ‘a-theorism’ , as favouring the biological medical model. Although initially exclusively devised for the use of the American psychiatrists, to the surprise of its authors it was rapidly accepted in all countries and the WHO adopted ﬁ  nally its principles in its own 
nosological system, the International Classiﬁ  cation of Diseases. 
Originally the result of a brutal reversal of trends in the American psychiatry, it expressed a general change of direction in the psychi-atric way of thinking towards the afﬁ  rmation, against the forces 
believed to threaten it of the medical character of psychiatry.
Crisis in psychiatry?
At ﬁ rst glance, the new status of psychiatry seems to have taken 
ﬁ rm root in the last three decades. It rests on the general acceptance 
of the medical deﬁ  nition of the concept of mental disease and of 
the progressive realization of a diversiﬁ  ed but co-ordinated institu-

tional system of mental health care. The biological perspective, even if it has taken a prominent place in research and therapy, is now combined with psychological and social approaches in the bio-psychosocial model. The psychiatrist, in accordance with his medical professional responsibilities, occupies a central position in a multidisciplinary team whose members contribute their special competences to the common goal.This idyllic picture is far from a reﬂ  ection of reality, even in the

developed countries, and the existence of a crisis in psychiatry is evoked with increasing frequency. An indication of the loss of prestige of psychiatry in the medical profession is the alarming decrease of the proportion of American medical students choosing a psychiatric residency; it fell to 2 per cent in 1990, a level much too low to ensure the maintenance of the present demography. Under the pressure of economic constraints, efforts are made everywhere to control the rising burden of medical care. They have taken different forms according to the country—from the managed care system in the United States to the numerus clausus  system in France, 
in which the number of internships available is determined by 
the government—but their common aim is to limit the number of

psychiatrists and the cost of their activities. Paradoxically, the recognition of the frequency of the mental disorders and the growing demand for psychiatric treatments has been associated with a reduction in the domain of action of psychiatrists, who are now often vastly outnumbered by clinical psychologists and social workers. In the United States, by 1990, 80 000 ‘clinical’ social work-ers were active in the psychiatric socio-psychological domain, a quarter of them in part- or full-time private practice. The claims of these powerful professional groups are not limited to a completely autonomous status but, in the case of the clinical psychologists, extend to the demand for a legal recognition of such typical ‘medical privileges’ as the right to hospitalize patients and to prescribe drugs. Even within medicine, psychiatry is under attack. In Germany, a medical psychotherapeutic specialty distinct from psychiatry has been created. The most impressive change has been in the

drugs. Even within medicine, psychiatry is under attack. In Germany, a medical psychotherapeutic specialty distinct from psychiatry has been created. The most impressive change has been in the proportion of mental disorders being now treated by general practitioners as a result of the availability of psychotropic drugs with fewer side-effects; in France, 60 per cent of antidepressants are now prescribed by general practitioners. These examples may not be a fair representation of the global picture, but there is undoubtedly a movement towards a limitation of the psychiatric specialty to the care of the most severe cases—in practice, the psychotic cases. However, some neuroscientists raise doubts about the usefulness of maintaining psychiatry as a specialty even in this ﬁ eld. Inﬂ  uential biologically oriented psychiatrists have recently

proposed on theoretical and practical grounds, that psychiatry should be absorbed into a new medical discipline, akin to the former neuropsychiatry, and all or most of its socio-psychological aspects should be left to non-medical professions.
Since psychiatry has emerged as a specialty, it has been submitted 
to conﬂ  icting forces. The demands of society, changes in the con-
cept of mental disorder and of its limits, variations in the role played by different theoretical perspectives, and successive scientiﬁ  c 
discoveries have been responsible for an evolution reﬂ  ected in the 
professional status and role of the psychiatrist. Displacements of the centre of gravity of a complex structure in which biological, psychological, and social factors interact have modiﬁ  ed the image 
of psychiatry. The threat of being incorporated in other medical specialties or being deprived of its medical character is but another transitory episode in its history.

Hunter, R. and Macalpine, I. (1963). Three hundred years of psychiatry 
1535–1860 . Oxford University Press, London.
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Postel, J. and Questel, U. (ed.) (1994). Nouvelle histoire de la psychiatrie .
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Shorter, E.A. (1997). History of psychiatry: from the era of the asylum to the 
age of Prozac . Wiley, New Y ork.
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gesamte Neurologie und Psychiatrie ,38, 161–275.2. Leigh, D. (1961). The historical development of British psychiatry . Vol. I, 
Eighteenth and nineteenth centuries . Pergamon Press, Oxford.
3. Goldstein, J. (1987). Console and classify: the French psychiatric profession 
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4. Zilboorg, G. (1941). A history of medical psychology . Norton, New York.
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6. Sabshin, M. (1983). Preface. In International perspectives on DSM-III
(ed. R.L. Spitzer, J.B.W. Williams, and A.E. Skodol). American Psychiatric Press, Washington, DC.1.4 the history of psychiatry as a medical specialty

Contents
 1.5.1 Psychiatric ethics
in clinical psychiatry
1.5.1 Psychiatric ethics
A myriad of ethical problems pervade clinical practice and research 
in psychiatry. Y et with few exceptions,(1–3) psychiatric ethics has 
generally been regarded as an addendum to mainstream bioethics. An assumption has been made that ‘tools’ developed to deal with issues like assisted reproduction or transplant surgery can be used essentially unmodiﬁ  ed in psychiatry. These tools certainly help the 
psychiatrist but the hand-me-down approach has meant that salient features of psychiatric ethics have been prone to misunder-standing. Psychiatric ethics is concerned with the application of moral rules to situations and relationships speciﬁ  c to the ﬁ  eld of

mental health practice. We will focus on ethical aspects of diagnosis and treatment that challenge psychiatrists, and on codes of ethics. Resolution of ethical dilemmas requires deliberation grounded in a moral theoretical framework that serves clinical decision-making, and we conclude with our preferred theoretical perspective.
Diagnostic issues
Conferring a diagnosis of mental illness on a person has profound ethical sequelae since the process may embody substantive adverse effects, notably stigma, prejudice, and discrimination (e.g. limited job prospects, inequitable insurance coverage). Furthermore, those deemed at risk to harm themselves or others may have their civil rights abridged. These consequences justify Reich’s
(4) call for the 
most thorough ethical examination of what he terms the clinician’s ‘prerogative to diagnose’ .Psychiatrists strive to diagnose by using as objective criteria as

most thorough ethical examination of what he terms the clinician’s ‘prerogative to diagnose’ .Psychiatrists strive to diagnose by using as objective criteria as 
possible and information gained from previous clinical encounters. The process is relatively straightforward when ﬁ  ndings such as 
gross memory impairment and life-threatening social withdrawal strongly suggest severe depression. Other situations are not so obvious. For instance, the distress felt by a bereaved person may incline one clinician towards diagnosing clinical depression where-as another may construe the picture as normal grief. Expertise, peer review, and benevolence combine to protect against arbitrariness and idiosyncrasy. Notwithstanding, psychiatrists must, to some extent, apply what might be termed as ‘reasoned subjectivism’ . Thus, speciﬁ  ed criteria in the American Psychiatric Association’s 
(APA) DSM-IV
(5) and the World Health Organization’s ICD-10(6)

do not preclude debate about the preciseness or legitimacy of syn-dromes like Attention Deﬁ  cit Hyperactivity Disorder (ADHD) and 
sexual orientation disturbance. Concern about the intrusion of value judgements into contemporary classiﬁ  cation has led to the 
contention that some diagnoses reﬂ  ect pejorative labelling rather 
than scientiﬁ  c decisions. For example, charges of sexism were lev-
eled against DSM-III
(7) on the grounds that masculine-based 
assumptions shaped criteria, resulting in women receiving unwar-ranted diagnoses like premenstrual dysphoria.
(8)
The issue central to this debate is whether certain mental states 
are grounded in fact or value judgements. Szasz(9) takes a radical 
position, arguing that disordered thinking and behaviour are due to objective abnormalities of the brain whereas mental illness per se

is a ‘myth’ , created by society in tandem with the medical profession in order to exert social control. The ‘anti-psychiatrist movement’
(10,11)
posits that mental illnesses are social constructs, reﬂ  ecting devia-
tions from societal norms. This argument is supported by the role of values in both deﬁ  ning homosexuality in the past as a psychiatric 
disorder, then reversing that position, in the case of American psy-chiatry through a ballot among members of the APA in 1973.
(12)
Legitimate diagnoses necessarily combine aspects of fact and value, as Wakeﬁ  eld
(13) avows in his conception of ‘harmful dysfunction’ . 
He views ‘dysfunction’ as a scientiﬁ  c and factual term, based in biol-

ogy, which refers to the failure of an internal evolutionary mecha-nism to perform a natural function for which it is designed and ‘harmful’ as a value-oriented term which covers the consequences of the dysfunction deemed detrimental in socio-cultural terms. Applying this notion to mental functioning, Wakeﬁ  eld describes 
beneﬁ  cial effects of natural mechanisms like those mediating 1.5
Ethics and values

29
cognition and emotional regulation, and judges their dysfunction 
harmful when it yields effects disvalued by society (e.g. self-destructive acts). Diagnosable conditions occur when the inability of an inter-nal mechanism to perform its natural function causes harm to the person. DSM-IV
(5) rightly emphasizes that mental disorders should 
not be diagnosed solely by reference to so cial norms. The deteriora-
tion of functioning by which schizophre nia is (partly) deﬁ  ned under 
Criterion B, or the norm violations of antisocial personality disor-der, must therefore be, in DSM-IVs phrase, ‘clinically signiﬁ  cant’ . 
What this amounts to, then, is that a negative value judgement is insufﬁ  cient to diagnose. The repercussions of these issues can be 
considerable, (e.g. exposing children erroneously labelled as ADHD to long-term medication with its attendant risks).
(14) A related

(14) A related 
matter, so-called ‘cosmetic psychopharmacology’ , involves the use of medication to enhance psychological functioning. As Kramer
(15)
notes, ﬂ  uoxetine may modulate emotions like anxiety, guilt, and 
shame, raising ethical questions regarding a person’s capacity to possess ‘two senses of self’ . Psychiatric diagnosis may also mitigate legal and personal results of one’s actions (e.g. interpreting exces-sive sexual activity as a variant of obsessive-compulsive disorder rather than as wilful).
Some of the worst perversions of psychiatry, in which it has been 
deployed as a form of social control, have been driven by misuse of its diagnostic concepts. In the former Soviet Union, for example, thousands of political, religious, and other dissidents were com mitted

to psychiatric hospitals on the basis of ‘delusions of reformism’ and other similar tainted concepts.
(16)
Treatment issues
Assessing and treating patients require a working alliance in con-junction with informed consent. Many psychiatric patients are in a position to understand and appreciate the nuances of treatment options, to express an informed preference, and to feel allied with a therapist in the task. When the process of informed consent is responsibly handled, particularly with reference to beneﬁ  ts and 
risks of therapeutic options, mentally ill people are in a comparable position to their counterparts in general medicine. This compara-bility is grounded in two concepts—competence
(17) and volun-
tarism. (18) The former satisﬁ  es the required criterion that the

tarism. (18) The former satisﬁ  es the required criterion that the 
person facing choices in treatment has the ‘critical faculties’ to appreciate the implications of each course of action. Voluntarism refers to a state in which the process of consent is devoid of any form of coercion. Obviously, given that the organ of decision-making is the same one that is impaired in many psychiatric condi-tions, profound ethical complications may ensue when seeking informed consent.
Other issues also present themselves in this context; these have 
been conveniently examined as a series of rights—to treatment, effective treatment, and refusal of treatment—and involuntary treatment.
The right to treatment
The asylum revealed tragically how this right was never actualized; the overcrowded institution became little more than a ware-house.
(19) Its custodial nature persisted even after the advent of 
psychotropics and psychosocial therapies. It took a plaintiff(20) to

psychotropics and psychosocial therapies. It took a plaintiff(20) to 
determine that a person committed involuntarily had the ‘right to receive treatment that would offer him a reasonable opportunity to be cured or to improve his mental condition’ . Diagnosed with 
schizophrenia in 1957, Kenneth Donaldson received minimal treatment for the next decade and a half. The US Supreme Court concluded in 1975 that a patient who does not pose a danger to himself or to others and who is not receiving treatment should be released into the community.
The right to effective treatment
The right to treatment has been revisited in subsequent judge-ments, predominantly in the United States.
(21) However, the right 
has lacked a guarantee that patients will receive effective treatment, reﬂ ected vividly in Osheroff v Chestnut Lodge (a private psychiat-

ric hospital in the United States). In this case, the plaintiff sued the staff for their failure to provide antidepressant treatment in the face of his deteriorating depression. Klerman
(22) subsequently 
argued that the clinician is duty-bound to use only’ ‘treatments for which there is substantial evidence’ ‘or seek a second opinion in the absence of a clinical response. Stone
(23) countered this 
position which he averred was tantamount to ‘. . . promulgating more uniformed scientiﬁ  c standards of treatment in psychiatry,

position which he averred was tantamount to ‘. . . promulgating more uniformed scientiﬁ  c standards of treatment in psychiatry, 
based on . . . opinion about science and clinical practice’ . Moreover, he posited that legal standards of care should not be established by one ‘school’ for the whole profession, even if enveloped in science. Instead, we should depend on ‘the collective sense’ of psychiatry, as well as apply the ‘respectable minority rule’ , namely that a relatively small group within psychiatry can legitimately devise novel therapies.
The right to refuse treatment

As a voluntary patient, Osheroff could have refused treatment of any type as part of informed consent. He pinpointed the institu-tion’s alleged failure to offer him an alternative treatment in the face of his worsening state with the therapy that was administered. If principles of informed consent had been applied correctly, his freedom to choose one treatment over others, and to withdraw consent at any stage thereafter, would have prevailed.
The situation differs radically when the patient is committed 
involuntarily to hospital or community treatment. The right to refuse treatment then looms large.
(24) A key event in this context 
was another US legal judgement when a court ruled that detained patients have a right to refuse treatment.
(25) This coincided with 
changing commitment laws in many jurisdictions from criteria 
linked to need for treatment to those highlighting the danger posed

linked to need for treatment to those highlighting the danger posed 
to oneself and/or others. The ethical repercussions are profound. 
If psychiatrists are empowered to detain a patient, is it not a con-
tradiction if they are then powerless to provide treatment should 
the person refuse? The argument rests on the premise that some-
one disturbed enough to warrant involuntary admission is axiom-atically entitled to treatment, and the psychiatrist well placed to give it. Without this arrangement, the psychiatrist’s functions are reduced to the custodial.
A countervailing argument is grounded in constitutional rights. 
Merely because people are committed does not mean they are inca-pable of participating in the process of informed consent. In the event they cannot appreciate the rationale for a course of action, a

Merely because people are committed does not mean they are inca-pable of participating in the process of informed consent. In the event they cannot appreciate the rationale for a course of action, a 
form of substituted judgement should be employed thereby ensur-ing that their rights remain prominent.
An assortment of legal remedies has emerged in response to this 
ethical quandary, ranging from a full adversarial process to reliance 1.5.1 psychiatric ethics

SECTION 1  the subject matter of and approach to psychiatry 30
on a guardian. Appelbaum(24) has contributed a lucid account of 
available options and a predilection for a treatment-driven model 
in which patients are committed because their capacity to decide about their medical care is lacking as part of their disturbed mental functioning. His own research demonstrates that most ‘refusing’ patients voluntarily accept treatment within 24 h.
(26)
In another pragmatically oriented account Stone(27) proposes 
that presumption of competence should be dealt with before admis-sion to hospital. Dealing with commitment and competence together obviates the problem of compulsory admission without the powers to treat. The snag is the ﬂ  uidity of the mental state. What patients 
think about treatment during the maelstrom of being detained may well change once they settle in and are suitably cared for.
Involuntary treatment

A consensus has prevailed universally that a proportion of psychi-atric patients lack the capacity for self-determination. They are prone to harming themselves and/or others, acting in ways they will later regret (e.g. a manic patient’s sexual indiscretions); and suffer from self-neglect (e.g. malnourished and physically ill schizo-phrenic patients). What is not universally agreed is how best to deal with such vulnerable people. Society has, generally, devised laws as the vehicle to respond to the thorny issue of how to protect this group. However, variations in legislation and its application are legion, reﬂ  ecting, in part, the ethical underpinnings of the process. 
Psychiatrists and society need to establish coherent arguments concerning relevant moral principles. A good start is Mill’s
(28)

(28)
contention that the ‘only purpose for which power can be rightfully exercised over any member of a civilized community, against his will, is to prevent harm to others. His own good, either physical or moral, is not a sufﬁ  cient warrant’ . Mill’s caveat that an exception 
must be made in the case of children and mentally disturbed people (i.e. ‘delirious’ or in a ‘state of excitement or absorption incompatible with the full use of the reﬂ  ecting faculty’) suggests 
they can legitimately be assisted.
Chodoff 
(29) has addressed the awesome question of compulso-
rily treating a person on the grounds of mental illness. He ﬁ  nds

Chodoff 
rily treating a person on the grounds of mental illness. He ﬁ  nds 
classical moral theory wanting and therefore proposes a ‘chastened and self-critical’ paternalism, one ‘willing to commit to strong safeguards against abuse’ . This humanism is epitomized in a con-cluding sentiment: involuntary treatment is not a conﬂ  ict of right 
versus wrong but one over the right to remain at liberty against the right ‘to be free from dehumanizing disease’ .
Our account hitherto has referred to patients as a homogeneous 
group. Loss of critical faculties may be a unifying feature but ethical factors will vary according to particulars of the clinical state. One noteworthy example is suicidal behaviour. Szasz
(30) sees

(30) sees 
suicide as the act of a moral agent. The State should therefore not assume power to prevent self-killing although it may opt to advise for or against. This argument is a libertarian one, with the corollary that everyone should have the right to end their life. Szasz has, however, neglected Mill’s
(28) point that when respecting a person’s 
right to liberty, a possible exception is loss of critical faculties. This is not to aver that all suicidal behaviour is the product of a disor-dered mind. Suicide in the wake of debilitating illness and a long-standing commitment to euthanasia, seems rational—for example, the British author, Arthur Koestler, left a suicide note demonstrat-ing that he arrived at his decision authentically and competently in terms of psychological function.
(31)The suicidal patient epitomizes the psychiatrist’s dilemma in 
having no choice but to impose treatment in various circumstances

having no choice but to impose treatment in various circumstances 
and having to declare a person’s incapacity, by dint of mental illness, to make rational judgements about what is in their best interests.
(32) Van Staden and Kruger(33) cover this topic by high-
lighting its dimensions, namely the failure to understand relevant information, choose decisively between options, and accept that the need for treatment prevails. They refer to the utility of a ‘functional approach’ in determining capacity, especially the temporal factor, so that a patient incapable of consenting at one point in their illness may become able at another. Ethical argu-ments to justify detention in a hospital can be extrapolated into the community setting. Similar restrictions on liberty lie at the heart of the moral dilemma and the psychiatrist again has to con-sider patients’ competence. Munetz and his colleagues
(34) apply

(34) apply 
three ethical arguments in a compelling fashion—utilitarian, com-munitarian, and beneﬁ  cence—concluding that all three support 
the use of compulsory treatment in the community setting. Advance directives are a means to obviate some of the ethical com-plications of compulsory treatment. In summary, patients prone to recurrence of their illness during which they may be too disturbed to provide informed consent reach an agreement with their psy-chiatrist about what constitutes the best course of action should they suffer an episode in the future and be unable to decide appro-priately what treatment is in their best interest. Given that several mental illnesses have a recurring course and are associated with incapacity, advanced directives would appear, on the face of it, to have a useful role. Empirical studies to examine this potential are a 
clear option; promising results have been achieved in work carried 
out hitherto.
(35)
Codes of ethics

(35)
The development of codes of ethics in the history of medicine reﬂ ects their possible role in promoting sound clinical practice 
(and research). Some codes have been a direct response to the collapse of professional standards—the Nuremberg Statement, for instance, was formulated in the aftermath of the Nazi medical crimes—but they obviously also have positive functions.
Promoting professional cohesion is one such function. Despite

Promoting professional cohesion is one such function. Despite 
George Bernard Shaw’s depiction of professions as ‘conspiracies against the laity’ and the risk that professional codes may indeed be self-serving—a charter for restrictive practices, protectionist rather than protective—a profession can only function effectively if it is cohesive and acts in a collegial way. Thus, a code which sets out its members’ obligations to one another can contribute substantially to achieving this goal. Most codes have emphasized medicine’s 
tradition of commitment and dedication to society; some even call 
for ‘whistle blowing’ in appropriate circumstances.
A second function of codes is to enhance high standards of prac-
tice. Professions are characterized, in part, by a corpus of special-ized knowledge and skills, not readily available to others, and offered to a dependent, often vulnerable clientele.
(36) T o the extent,

(36) T o the extent, 
therefore, that it takes an expert to judge relevant expertise, a degree of self-regulation is essential. But this must be balanced by external 
monitoring. Where bad practice becomes the norm, self-regulation may reinforce it: the abuse of psychiatry to suppress dissent in the 
former Soviet Union was, in effect, promoted by leaders of the pro-fession.
(16) It can be argued that a prescriptive ethical code is

31
unnecessary, since implicit discipline and a shared ethos sufﬁ  ce to 
maintain standards. As we have noted, history contradicts this, with 
codes often appearing as a response to compromised care. What kind of codes best promote sound practice will vary with circum-stances. They have therefore differed widely in form and content, ranging from aspirational principles to practice guidelines which are set out in considerable detail. The latter are pertinent, especially for education and training. The code of the Royal Australian and New Zealand College of Psychiatrists
(37) and the American 
Psychiatric Association(38) combine general principles with a series 
of annotations on speciﬁ  c areas such as conﬁ  dentiality, respect for

of annotations on speciﬁ  c areas such as conﬁ  dentiality, respect for 
professional boundaries, and informed consent. Codes also vary in ethical focus, some are virtue-driven, emphasizing character traits which support best possible practice whereas others are duty-based in that they lay out speciﬁ  c responsibilities and obligations.
Codes thus have several meritorious purposes. Furthermore, 
these support one other. For instance, their inherent educational quality serves to enhance sound ethical clinical practice and their stipulation of potential hazards in ethical decision-making may prevent compromised care, even misuse of expert knowledge.
Conclusion

We have readily noted how the psychiatrist faces ethical quandaries at several levels, both diagnostically and therapeutically, and the potential role of codes of ethics to grapple with them. Diverse moral theories have also been promulgated to aid the practitioner
(1,2)
and we conclude with our own preferred approach, a combination of principlism
(39) and care ethics.(40) Principlism (or principle-
based ethics) relies on a set of well-recognized moral principles to identify and analyse ethical problems: respect for autonomy (liter-ally self-government), non-maleﬁ  cence (ﬁ  rst of all, do no harm), 
beneﬁ  cence (acting in peoples’ best interests), and justice (treating 
people fairly). The essence of care ethics revolves around the ‘natural’ propensity of health professionals to extend care to depen-dent, vulnerable people and to react with such ‘moral’ feelings as compassion, sensitivity, and trustworthiness.
(40) The approach ﬁ  ts

(40) The approach ﬁ  ts 
well with psychiatry since its practitioners depend day in, day out, on empathy in order to understand the interests and needs of patients and their families. A synthesis of care ethics and princi-plism permits sound moral reﬂ  ection within an emotionally based 
environment in which connectedness between patient and thera-pist is paramount. We believe this approach, a complementarity between feeling and reason, acknowledges and best exploits the role of ‘moral emotions’
(41) when clinicians are presented with the 
many, nuanced ethical conundrums of psychiatric practice.
Bloch, S. and Green, S. (eds.) (1999). Psychiatric ethics  (3rd edn). 
Green, S. and Bloch, S. (2006). An anthology of psychiatric ethics .
Post, S. (ed.) (2004). Encyclopedia of bioethics  (3rd edn). Macmillan, 
New Y ork.

New Y ork.
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 3. Dickenson, D. and Fulford, W. (2001). In two minds: a casebook of 
psychiatric ethics . Oxford University Press, Oxford.
 4. Reich, W. (1999). Psychiatric diagnosis as an ethical problem. 
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Chicago.
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12. Stoller, R., Marmor, J., Bieber, I., et al.  (1973). A symposium: should 
homosexuality be in the APA nomenclature. American Journal of 
Psychiatry ,130,1207–16.
13. Wakeﬁ  eld, J. (1992). The concept of mental disorder: on the boundary 
between biological facts and social values. American Psychologist ,47,
373–88.
14. Halasz, G. (2002). A symposium of attention deﬁ  cit hyperactivity

373–88.
14. Halasz, G. (2002). A symposium of attention deﬁ  cit hyperactivity 
disorder (ADHD): an ethical perspective. Australian and New Zealand 
Journal of Psychiatry ,36, 472–5.
15. Kramer, P . (1993). Listening to Prozac . Viking, New Y ork.
16. Bloch, S. and Reddaway, P . (1977). Russia’s political hospitals .
Gollancz, London (Published in the US as Psychiatric Terror ,
New Y ork: Basic Books).
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study of decision making in psychiatry . Guilford, New Y ork.
18. Roberts, L. (2002). Informed consent and the capacity for voluntarism. 
American Journal of Psychiatry ,159, 705–12.
19. Bloch, S. and Pargiter, R. (2002). A history of psychiatric ethics. 
Psychiatric Clinics of North America ,25, 509–24.
20. Donaldson v O’Connor, F. 2d 5th Cir, decided Apr. 26, 1974; 
O’Connor v Donaldson 422US. 563, 1975.

21. Wyatt v Stickney 325F Supp 781 (1971); Wyatt v Stickney 344F Supp 
373, 376, 379–85 (1972).
22. Klerman, G. (1990). The psychiatric patient’s right to effective 
treatment: implications of Osheroff v Chestnut Lodge. American 
Journal of Psychiatry ,147, 419–27.
23. Stone, A. (1990). Law, science, and psychiatric malpractice: a response 
to Klerman’s indictment on psychoanalytic psychiatry. American 
24. Appelbaum, P . (1988). The right to refuse treatment with antipsychotic 
medications: retrospect and prospect. American Journal of Psychiatry ,
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25. Rogers v Okin, 478F Supp 1342 (D Mass, 1979); Rogers v 
Commissioner of the Department of Mental Health, 458NE 2d 308 
(Mass Sup Jud Ct, 1983).
26. Appelbaum, P . and Gutheil, T. (1979). ‘Rotting with their rights on’:

26. Appelbaum, P . and Gutheil, T. (1979). ‘Rotting with their rights on’: 
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27. Stone, A. (1981). The right to refuse treatment: why psychiatrists 
should and can make it work. Archives of General Psychiatry ,
38, 358–62.
28. Mill, J.S. (1976). On liberty. In Three essays . Oxford University Press, 
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29. Chodoff, P . (1984). Involuntary hospitalisation of the mentally ill as a 
moral issue. American Journal of Psychiatry ,141, 384–9.
30. Szasz, T. (1986). The case against suicide prevention. American 
Psychologist ,41, 806–12.
31. Cesarani, D. (1998). Arthur Koestler: the homeless mind . Heinemann, 
London.
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ethics  (ed. S. Bloch, P . Chodoff, and S. Green) (3rd edn). Oxford 
University Press, Oxford, pp. 441–60.
33. Van Staden, C. and Kruger, C. (2003). Incapacity to give informed 
consent owing to mental disorder. Journal of Medical Ethics ,29, 41–3.
34. Munetz, M., Galon, P ., and Frese, F. (2003). The ethics of mandatory 
community treatment. Journal of the American Academy of Psychiatry 
and the Law ,31,173–83.
35. Green, S. and Bloch, S. (2006). An anthology of psychiatric ethics .
Oxford University Press, Oxford. pp. 183–84.

36. Fullinwinder, R. (1994). Codes of ethics and the professions
(ed. M. Coady, S. Bloch). Melbourne University Press, Melbourne, pp. 72–87.
37. Royal Australian and New Zealand College of Psychiatrists. (2001). 
Code of ethics  (3rd edn). Melbourne.
38. American Psychiatric Association. (2001). Principles of medical 
ethics with annotations especially applicable to psychiatry  (5th edn). 
APA, Washington, DC.
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(5th edn). Oxford University Press, New Y ork.
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the moral compass  (ed. C. Calhoun). Oxford University Press, New Y ork, 
pp. 176–88.
41. Hume, D. (1969). A treatise of human nature . Penguin, 
Harmondsworth.
1.5.2 Values and values-based 
practice in clinical psychiatry

Values-based practice is a new skills-based approach to working 
more effectively with complex and conﬂ  icting values in health 
and social care. This chapter illustrates some of the ways in which combining values-based with evidence-based approaches supports the day-to-day practice of the clinical psychiatrist, particularly in the context of multidisciplinary teamwork.
What are values?

Perhaps one of the most familiar ways in which values impact medicine is by way of ethics. But values are wider than ethics. Ethical values are indeed one kind of value. But there are many other kinds of values, such as aesthetic and prudential values. Values also extend to needs, wishes, preferences, indeed to any and all of the many different ways in which we express negative or posi-tive evaluations and value judgments. Within each and all of these areas, moreover, there are wide differences in the particular values held by different individuals, by different cultures, and at different historical periods.Given the breadth and complexity of values, it is small wonder 
that the term ‘values’ means different things to different people. This is illustrated by Table 1.5.2.1 which lists the responses of a group of trainee psychiatrists when asked, at the start of a training session on val ues-based practice, to write down three words or short

phrases that they associate with ‘values’ . As the table shows, although there is some overlap, every member of the group came up with a different set of associations.
If our values are diverse, however, they are not completely idiosyn-
cratic. T o the contrary, there are many values that are widely shared, at least within a given group at a particular period. The values of patient autonomy (freedom of choice) and of acting in the patient’s best interests, for example, are shared values that underpin con-temporary medical ethics, and these two values are indeed among the values evident in Table 1.5.2.1.
It is the diversity of human values, and how this can be linked with 
the shared ethical values underpinning clinical practice, that is the starting point for values-based practice. There is a sense in which medicine has always been values-based just as there is a sense in which it has always been evidence-based.
(1) The need for values-

based practice in contemporary practice, again like the need for evidence-based practice, arises from the growing complexity of medicine; the growing complexity of the evidence underpinning med-icine has led to the need for the new tools of evidence-based medi-cine; the growing complexity of the values underpinning medicine has led to the need for the new tools of values-based medicine.
The growing complexity of values, as well as evidence, is particu-
larly evident in psychiatry. ‘Autonomy’ and ‘best interests’ , for example, although both shared ethical values, are often in tension. In the past, most people were content to allow doctors to decide what is in their best interests and this is still the case in many parts of the world.
(2) Increasingly though, at least in Europe and North 
Table 1.5.2.1  What are values?
Faith
Internalization
Acting in best interestsHow we treat people
Attitudes
Principles
Autonomy
Integrity
Conscience
Best interests

Faith
Attitudes
Autonomy
Integrity
AutonomyLove
Relationships
Respect
Personal
Difference . . . diversityNon-violence
Compassion
Dialogue
Beliefs
Right/wrong to me
What I amResponsibility
Accountability
Belief
PrinciplesThings held dearWhat I believe
What makes me tickWhat I won’t compromise
Subjective merits
Meanings
Person-centred care‘Objective’ core
Conﬁ  dentiality
Autonomy
A standard  for the way I conduct myself
Belief about how things should  be
Things you would not want to changeSigniﬁ  cant
Standards
Truth

33
America, a growing emphasis on patient autonomy has led to 
complex interactions between these two values in clinical care. 
In particular, autonomy and best interests come into direct conﬂ  ict 
in relation to issues of compulsory treatment (Chapter 1.5.1). Then 
again, even considered in isolation, ‘best interests’ have highly com-plex applications in practice, in the sense that what is ‘best’ for one person may be very different from what is ‘best’ for another, according to differences in their personal values and the values of others concerned. Establishing ‘best interests’ thus presents particular challenges in areas such as old age psychiatry, for example, where patients may lack the decision-making capacity to exercise genuine autonomy on their own behalf.
One response to the growing complexity of the values bearing on 
clinical practice is to write ever more detailed rules aimed at ﬁ  xing

clinical practice is to write ever more detailed rules aimed at ﬁ  xing 
in advance the ‘right outcomes’ for any given clinical situation. It is this response that is driving the growing volume of ethical codes and regulatory bodies concerned with medicine. Values-based practice offers quite a different albeit complementary response. It switches the focus from pre-set right outcomes  to a reliance on 
good process . Values-based practice, that is to say, focuses not so 
much on what  is done but on how it is done. Starting from the 
‘democratic’ ethical premise of respect for differences of values, values-based practice relies on good process (in particular good clinical skills, see below) to support balanced decision-making within the framework of shared values deﬁ  ned by codes of ethical 
practice.
(3)
Values-based and evidence-based medicine

practice.
(3)
Values-based and evidence-based medicine 
As a process-based approach to clinical decision-making, values-based practice is complementary not only to regulatory ethics but also to evidence-based practice. The processes of values-based practice and of evidence-based practice are of course very different. Evidence-based practice, as John Geddes describes (Chapter 1.10), relies on statistical and other methods for combining evidence from methodologically sound research. Values-based practice, by contrast, relies primarily on learnable clinical skills. There are other components of the process of values-based practice, including a number of speciﬁ  c links between values-based and evidence-based 
practice.
(3) But at the heart of values-based practice are four areas 
of clinical skill. As set out more fully in Table 1.5.2.2, these are, raised awareness of values and of differences of values, reasoning about values, knowledge of values, and communication skills.

The close interdependence of values-based and evidence-based 
approaches has been well recognized by many of those involved in the development of evidence-based medicine. Indeed, there is per-haps no clearer statement of this inter-dependence than the very deﬁ nition of evidence-based medicine given by David Sackett and 
his colleagues in their book, Evidence-Based Medicine: How to 
Practice and Teach EBM .
(1) Evidence-based medicine is standardly 
thought to be concerned only with research evidence, as outlined above. T o the contrary, Sackett et al . say (p. 1), evidence-based 
medicine combines three distinct elements. The ﬁ  rst element is,

medicine combines three distinct elements. The ﬁ  rst element is, 
certainly, best research evidence. In clinical practice, however, best research evidence has to be combined with the experience and skills of practitioners, and, crucially, with patients’ values. ‘By patients’ values’ , Sackett et al . continue, ‘we mean the unique preferences, 
concerns and expectations each patient brings to a clinical encounter and which must be integrated into clinical decisions if they are to serve the patient’ . Furthermore, they conclude, it is only ‘when these 
three elements (best research ‘evidence, clinicians’ experience and patients’ values) are integrated, (that) clinicians and patients form a diagnostic and therapeutic alliance which optimizes clinical out-comes and quality of life.’
Values in the multidisciplinary team

In many parts of the world, psychiatric services are increasingly delivered through multidisciplinary and multi agency teams (Chapter 1.8.1). The move to  multidisciplinary team-working 
reﬂ ects a broadly evidence-based recognition that different profes-
sional groups offer different but complementary resources of knowledge and skills. It was realized early on, however, that differ-ences of perspective (which include different value perspectives) between different profes sional groups may lead to communication and other problems of effective team-working.
(4,5) This is where

(4,5) This is where 
values-based practice can help to support the leadership role of the clinical psychiatrist in the multidisciplinary team. T o anticipate a little, values-based practice, as we will see in this section and the next, 1) helps to make differences of perspective between team members more transparent, thus improving communication and shared decision-making; and 2) converts these differences of per-spective between team members from a barrier into a positive resource for de cision-maki ng that is sensitive to the particular and Table 1.5.2.2  The four key skills areas underpinning values-based 
practice
Skills area Applications in values-based practice
1.  Raising 
Awareness of 
ValuesValues, our own and those of others, are often implicit: 
thus a ﬁ  rst step towards balanced decision-making is to raise awareness,
1) of values as such,
2) of differences of values,
(See text)
2.  Reasoning 
about ValuesIn ethics and law, various methods of reasoning are used

(See text)
about ValuesIn ethics and law, various methods of reasoning are used 
to derive ethical conclusions.
In values-based practice, the same range of methods is 
used but primarily to explore and open up the range of 
values bearing on a given situation.
These include principles, casuistry (case-based 
reasoning), utilitarianism (balancing utilities, used 
especially in health economics), and deontology 
(rule-based reasoning, used especially in law).
(See Further information)
3.  Knowledge of 
ValuesValues-based practice draws on evidence about values 
derived from,
1) the full range of empirical methods (including 
qualitative social science methods),
2) a range of philosophical methods,
3) combined methods (see text, also Further Reading).
4.  Communication 
SkillsIn values-based practice, communication skills are 
central to,
1) eliciting and unders tanding individual values,

2) resolving conﬂ  icts of values, for example by 
negotiation and conﬂ  ict resolution (see text).1.5.2 values and values-based practice in clinical psychiatry

SECTION 1  the subject matter of and approach to psychiatry 34
often very different values—the needs, wishes, preferences, etc.—of 
individual patients and their families.
First, then, what are the differences of perspective between dif-
ferent team members? The perhaps surprising extent of these dif-ferences is illustrated by Table 1.5.2.3. This is based on a study, led by the British social scientist, Anthony Colombo, of multidisci-plinary teams in the UK concerned with the community care of people with long-term schizophrenia.
(6) T o understand the signiﬁ  -
cance of Table 1.5.2.3, we need to look brieﬂ  y at the background to 
Colombo’s study and how it was carried out.
Colombo was interested in implicit models of disorder and 
how such models might inﬂ  uence the processes of decision-making

how such models might inﬂ  uence the processes of decision-making 
in day-to-day clinical care within multidisciplinary teams. Asked directly, most team members, from whatever professional background, will indicate that they share much the same broadly biopsychosocial model of schizophrenia. This is their shared explicit
model, then. The hypothesis guiding Colombo’s study, however, was that, notwithstanding their explicit commitment to a shared biopsychosocial model, in actual practice different team members would be guided by different implicit  models. These different implicit 
models reﬂ  ected different weightings or priorities (hence values), 
in turn reﬂ  ecting differences of professional background and training,

in turn reﬂ  ecting differences of professional background and training, 
that different team members might attach to the different aspects of a given case. Their different implicit models, furthermore, just in being implicit rather than explicit, could help explain the difﬁ  cul-
ties of communication and other problems of shared decision-making within multidisciplinary teams that had been identiﬁ  ed in 
the literature (as above).
The aim of Colombo’s study, therefore, was to access the implicit

models (including values) guiding different professional groups in their responses to patients with schizophrenia. Colombo’s method, correspondingly, was indirect rather than direct. He presented subjects with a standardized case vignette, of a man called ‘T om’ , with features of schizophrenia (though without using that term as such), and then explored their responses using a semi-structured interview and carefully validated scoring system. In previous work, Colombo had shown how different models of disorder (six of which are represented by the columns in Table 1.5.2.3) could be analysed 
Table 1.5.2.3  Comparison of models grids for psychiatrists and social workers (shared elements of models shown highlighted)
Models - Psychiatrists
Elements Medical (Organic) Social stress Cognitive behaviour Psychotherapeutic Family (interaction) Political
 1. Diagnosis/Description P

 2. Interpretation of Behaviour P 3. Labels P 4. Aetiology P 5. Treatment P 6. Function of the Hospital PP P
 7. Hospitality & Community P
 8. Prognosis P 9. Rights of the Patient P
 10. Rights of Society P
 11. Duties of the Patient P P
 12. Duties of Society P
Models - Social Workers
 1. Diagnosis/Description S
 2. Interpretation of Behaviour S 3. Labels S
 4. Etiology S
 5. Treatment S S 6. Function of the hospital SS S
 7. Hospitality & Community S S
 8. Prognosis S
 9. Rights of the Patient S S S
 10. Rights of Society S
 11. Duties of the Patient S
 12. Duties of Society S

35
and compared along 12 key dimensions (diagnosis, causal factors, 
etc.) as represented by the lines in Table 1.5.2.3. Responses to the 
semi-structured interview thus allowed a proﬁ  le to be developed 
for each subject, and cumulatively for each professional group, of their implicit models. These proﬁ  les, or ‘models grids’ , gave an 
overall picture of the implicit model on which an individual or group was drawing in their responses to T om.
It is the ‘models grids’ for psychiatrists and psychiatric social 
workers respectively that are compared in Table 1.5.2.3. As this shows, notwithstanding their shared explicit commitment to a bio-psychosocial model, psychiatrists and social workers, working in similar teams in the same area of the UK, had widely different implicit  models. Direct comparison of the two models grids shows

that psychiatrists and approved social workers coincided on only six out of a total possible of 72 elements! Small wonder, then, given that team members were unaware of these differences of implicit models, that difﬁ  culties of communication and of shared decision-
making often arose. They all accepted an explicitly biopsychosocial approach. But their different professional perspectives, including value perspectives, led them to attach very different priorities to different aspects of ‘T om’ , and, by extension, to the real patients with whom they were concerned in the real world of day-to-day multidisciplinary care.
Values-based practice in the 
multidisciplinary team
Colombo’s study illustrates how careful research may improve our 
knowledge of values (skills area 3, Table 1.5.2.2 above) and his research has subsequently been adapted and developed as part of a training manual for values-based practice.
(7) Research is as impor-

tant in values-based practice as in any other aspect of medicine. There is a widespread assumption that understanding each other’s values is a matter of relatively transparent intuition. But in addition to empirical studies, surveys,
(8) patient narratives,(9) and 
other sources all point to the extent to which our perceptions of each other’s values are often misperceptions. Colombo’s study also 
illustrates the inter-dependence of the four skills areas. As a contri-bution to skills area 3 (knowledge), the study also contributes to raising awareness of values and of differences of values (skills area 1) in the speciﬁ  c context of multidisciplinary team working.
Merely raising awareness of differences of implicit models may

Merely raising awareness of differences of implicit models may 
itself be enough to improve communication between team members and hence, shared decision-making as the basis of effective multi-disciplinary care. There are circumstances, however, in which rais-ing awareness may not be sufﬁ  cient. Where team values are directly 
conﬂ  icting, for example, raising awareness may even have the effect 
of accentuating rather than reducing difﬁ  culties of shared decision-
making. So, how should differences of values be managed? Different 
responses are possible here. One approach is to try to create a homog-
enized composite model. At a relatively abstract level, this is what the biopsychosocial model offers. A different response is to seek to estab-lish a ‘top’ model that takes priority over all other models. It is a natu-ral enough assumption of any given professio nal group that their 
own particular model should be the ‘top’ model.

Rather than either a composite model or a ‘top’ model, values-
based practice suggests that differences of value perspective, as incorporated into implicit models of disorder, far from being sup-pressed should be acknowledged and built on as a positive resource for effective multidisciplinary teamwork. This is essentially because, 
as the models grids in Table 1.5.2.4 show, differences in implicit models between different team members reﬂ  ect corresponding dif-
ferences among patients themselves .
The models grids in Table 1.5.2.4 were derived in Colombo’s

The models grids in Table 1.5.2.4 were derived in Colombo’s 
study using precisely the same methods as the models grids for the professional groups (i.e., using the same standardized case vignette, interview schedule, etc.). The patients involved in Colombo’s study, however, were not recruited through multidisciplinary teams. Rather, they were recruited as volunteers from local MIND, a mental health NGO in the UK that ‘advocates for patients’ rights. T o volunteer for the study, a patient had to have had a diagnosis of schizophrenia for at least three years. There was no requirement that they should agree with the diagnosis. Rather, the aim was to explore the implicit models of a group of subjects who had had this diagnosis ‘willing or no’ for an extended period. The expecta-tion in the study was that this group of patients, recruited in this way, would include a signiﬁ  cant number with a ‘political’ , or

‘anti-psychiatric’ , model of disorder, represented by the right-hand column of the models grids. In fact, as Table 1.5.2.4 shows, the patient group divided naturally into two sub-groups, one with implicit models very close to those of the psychiatrists in the study, the other with implicit models very close to those of the social workers.
The correlation in Colombo’s study between different profes-
sional models and different patient models, gives a whole new values-based rationale for multidisciplinary teamwork. From an evidence-based perspective, multidisciplinary team working offers a diversity of knowledge and skills in meeting patients’ needs. From 
a values-based perspective, multidisciplinary team working brings,

a values-based perspective, multidisciplinary team working brings, 
in addition to different knowledge and skills, different value perspectives. In a well-functioning multidisciplinary team, these different value perspectives can help to ensure that professionals’ knowledge and skills are matched appropriately to the different values—the needs, wishes, preferences, etc.—of individual patients and their families.
In helping to bring together the different perspectives of team

In helping to bring together the different perspectives of team 
members in a positive and well-balanced way, values-based prac-tice thus, directly supports the leadership role of the consultant psychiatrist in the multidisciplinary team. Again, all four skills areas of values-based practice are closely interdependent here. In addition to knowledge of values, the reasoning skills noted in Table 1.5.2.2 may be helpful. Good communication skills are also crucial. As Table 1.5.2.2 indicates, these include in particular, skills for eliciting and understanding values, and where values conﬂ  ict, 
skills of negotiation and conﬂ  ict resolution.
Conclusions
This chapter has introduced a number of key points about values-
based practice (summarized in Table 1.5.2.5) as a new skills-based approach to working more effectively with complex and conﬂ  icting

based practice (summarized in Table 1.5.2.5) as a new skills-based approach to working more effectively with complex and conﬂ  icting 
values. The importance of values-based as well as evidence-based approaches has been illustrated particularly by reference to the leadership role of the consultant psychiatrist in the multidisci-plinary team. Multidisciplinary team-working is of course not unique in its requirement for values-based as well as evidence-based approac hes. As Sackett et al.
(1) reminded us at the start of this 
chapter, it is only by combining best research evidence with practi-tioners’ knowledge and skills and with patients’ values, that we can 1.5.2 values and values-based practice in clinical psychiatry

SECTION 1  the subject matter of and approach to psychiatry 36
build the ‘diagnostic and therapeutic alliance’ on which in any area 
of medicine, good clinical care crucially depends.
Two further points are worth adding in conclusion. The ﬁ  rst is 
that values-based practice as introduced here, as being based pri-marily on learnable clinical skills, is only one among a number of new disciplinary resources supporting more effective ways of work-ing with complex and conﬂ  icting values in healthcare. Further and 
quite different resources are provided by such empir ical disciplines as decision theory,
(10) for example, and health economics, an inno-
vative use of which has recently been developed by a group at the Centre for Value-Based Medicine in the States.
(11) Values-based

(11) Values-based 
practice itself is so underpinned by a branch of analytic philosophy, called philosophical value theory (see Further Reading, below) that, as an analytic discipline, it is a natural partner both of empirical research, as in Colombo’s study,
(12) and of other philosophical disci-
plines more familiar in psychiatry, notably phenomenology.(13) As 
Andreasen(14) has argued, these and other philosophical disciplines, have a growing practical importance not only in clinical psychiatry, 
as illustrated in this chapter, but also in the new neurosciences.
The second concluding point has to do with the place of psychia-

try as a science-led medical discipline in the 21st century. As the most value-laden area of medicine, psychiatry was widely stigmatized in the 20th century as being, at best, scientiﬁ  cally underdeveloped,
(15)
at worst outwith medicine altogether;(16) and debates about elimi-
nate values from psychiatric diagnostic concepts continue in the context of current revisions of the ICD and DSM classiﬁ  cations.
(17, 18)
Philosophical value theory, as the discipline underpinning values-
based practice, shows to the contrary that the value-ladenness of psychiatry, far from reﬂ  ecting any deﬁ  ciency in its science, is a

based practice, shows to the contrary that the value-ladenness of psychiatry, far from reﬂ  ecting any deﬁ  ciency in its science, is a 
direct consequence of the fact that psychiatry, in being concerned with the higher functions of emotion, desire, volition, sexuality, and so forth, is by the same token concerned with areas of experi-ence and behaviour where human value themselves are highly diverse (
(19), especially chapters 4 and 5, building on(20)).Table 1.5.2.4  Comparison of models grids for two groups of Patients—Group 1 similar to Medical Psychiatrists (Pt-Med), Group 2 similar to 
Social Workers (Pt-SW) (See also Table 1.5.2.3)
Models - Group 1 (similar to psychiatrists)
Elements Medical (Organic) Social stress Cognitive behaviour Psycho-therapeutic Family (interaction) Political
 1. Diagnosis/Description Pt-Med

 2. Interpretation of Behaviour Pt-Med Pt-Med 3. Labels Pt-Med 4. Aetiology Pt-Med 5. Treatment Pt-Med 6. Function of the hospital Pt-Med Pt-Med Pt-Med 7. Hospitality & Community Pt-Med Pt-Med 8. Prognosis Pt-Med 9. Rights of the Patient Pt-Med Pt-Med
 10. Rights of Society Pt-Med 11. Duties of the Patient Pt-Med Pt-Med 12. Duties of Society Pt-Med Pt-Med Pt-Med
Models - Group 2 (similar to social workers)
 1. Diagnosis/Description Pt-SW 2. Interpretation of Behaviour Pt-SW 3. Labels Pt-SW Pt-SW 4. Aetiology Pt-SW
 5. Treatment Pt-SW Pt-SW 6. Function of the hospital Pt-SW Pt-SW
 7. Hospitality & Community Pt-SW Pt-SW 8. Prognosis Pt-SW
 9. Rights of the Patient Pt-SW Pt-SW Pt-SW 10. Rights of Society Pt-SW 11. Duties of the Patient Pt-SW Pt-SW 12. Duties of Society Pt-SW Pt-SW

37
Psychiatry, therefore, in addition to being scientiﬁ  cally  complex, 
is shown by philosophical value theory to be evaluatively  complex. 
This is why it has been appropriate that values-based practice, as a skills-based approach to working with complex and conﬂ  icting 
values, should have developed ﬁ  rst in psychiatry. But with the 
growing complexity of the values bearing on all areas of medicine, 
it seems likely that, as Sackett et al. anticipated (as above), values-
based as well as evidence-based approaches will become increas-ingly crucial in the 21st century not only in psychiatry but across the board. The effect of this will be to reverse the 20th century stigmatization of psychiatry. Instead of being perceived as a scien-tiﬁ c also-ran, psychiatry, by being ﬁ  rst in the ﬁ  eld with values-based practice as an essential partner to evidence-based practice, will be 
seen to have led the way with a 21st century model of medicine that

seen to have led the way with a 21st century model of medicine that 
is not only fully science-based but also genuinely patient-centred.
Acknowledgments
The information on which Tables 1.5.2.3 and 1.5.2.4 are based is 
derived from the study of models of disorder described in the text and ﬁ  rst published in Colombo et al.  2003. 
(6)
1) Skills training for values-based practice
Woodbridge, K., and Fulford, K.W.M. (2004). Whose Values? A workbook for 
values-based practice in mental health care . London: Sainsbury Centre 
for Mental Health. (see website www.scmh.org.uk); also by mail from The Sainsbury Centre for Mental Health, 134–8, Borough High Street, London SE1 1LB
2) The theory of values-based practice
Fulford, K.W.M. (1989, reprinted 1995 and 1999). Moral Theory and 
Medical Practice . Cambridge: Cambridge University Press.
Fulford, K.W.M. (2004). T en Principles of Values-Based Medicine. Ch 14 In

Fulford, K.W.M. (2004). T en Principles of Values-Based Medicine. Ch 14 In 
The Philosophy of Psychiatry: A Companion  (ed. J. Radden), pp. 205–34. 
New Y ork: Oxford University Press. (Describes the links between values-based and evidence-based approaches in clinical decision-making).
3)  Values-based practice and the new philosophy of 
Fulford, K.W.M., Thornton, T., and Graham, G. (2006). The Oxford 
Textbook of Philosophy and Psychiatry . Oxford: Oxford University Press. 
(see especially chapter 18, setting values-based practice in context with more familiar approaches to ethics; and chapter 21, showing how values-based alongside evidence-based approaches are important 
in diagnostic assessment as well as in treatment and care 
planning).
 1. Sackett, D.L., Straus, S.E., Scott Richardson, W., et al. (2000). Evidence-

Based Medicine: How to Practice and Teach EBM (2nd edn.). Edinburgh and London: Churchill Livingstone.
 2. Okasha, A. (2000). Ethics of Psychiatric Practice: Consent, Compulsion 
and Conﬁ  dentiality. Curr Op in Psychiatry ,13, 693–8.
 3. Fulford, K.W.M. (2004). T en Principles of Values-Based Medicine. 
Ch 14 In The Philosophy of Psychiatry: A Companion  (ed. J. Radden), 
pp. 205–34. New Y ork: Oxford University Press.
 4. Clunis Report: North East Thames and South East Thames Regional 
Health Authorities. (1994). The Report of The Enquiry into the Care tnd 
Treatment of Christopher Clunis.  London: HMSO.
 5. Department of Health. (1999). Still Building Bridges: The Report 
of a National Inspection of Arrangements for the Integration of Care 
Programme Approach with Care Management . London: Department of 
Health.

Health.
 6. Colombo, A., Bendelow, G., Fulford, K.W.M., et al. (2003). Evaluating 
the inﬂ  uence of implicit models of mental disorder on processes of 
shared decision making within community-based multi-disciplinary teams. Social Science and Medicine ,56, 1557–70.
 7. Woodbridge, K., and Fulford, K.W.M. (2004). Whose Values? 
A workbook for values-based practice in mental health care . London: 
Sainsbury Centre for Mental Health.
 8.  Rogers, A., Pilgrim, D. and Lacey, R., (1993). Experiencing Psychiatry: 
Users’ Views of Services . London: The Macmillan Press.Table 1.5.2.5  Key points about values-based practice for clinical 
 1.  Values are wider than ethics and include all the many ways in which we 
express positive and negative evaluations, i.e., preferences, needs, wishes, 
etc. as well as ethical values

 2.  Values-Based Practice is a new skills-based approach to working with 
complex and conﬂ  icting values in medicine
 3.  Ethical principles provide a framework of shared values – such as ‘best 
interests’ and ‘autonomy of patient choice’ - that guide the outcomes  of 
clinical decision-making supported by codes of practice and regulatory 
bodies
 4.  Values-based practice is complementary to regulatory ethics in focusing 
on the process  of clinical decision-making: ethics focuses on ‘right 
outcomes’ (reﬂ  ecting shared values); values-based practice focuses on 
‘good process’ (reﬂ  ecting complex/conﬂ  icting values)
 5.  In focusing on process rather than outcomes, values-based practice

 5.  In focusing on process rather than outcomes, values-based practice 
(concerned with complex and conﬂ  icting values) is fully complementary to evidence-based practice (concerned with complex and conﬂ  icting 
evidence) in clinical decision-making
 6.  At the heart of the ‘good process’ on which values-based practice depends 
are four key areas of clinical skills: 1) awareness of values and of diversity 
of values, 2) reasoning about values, 3) knowledge of values, and 4) 
communication skills (including skills in such areas as negotiation and conﬂ  ict resolution)
 7.  Among other applications, values-based practice supports the role of 
the consultant psychiatrist in multidisciplinary teams by, 1) improving 
understanding of differences of values between different team members (thus improving communication and shared decision-making), and 2) 
improving understanding of the particular and often very different values

improving understanding of the particular and often very different values 
of individual patients and carers (thus improving the extent to which care and treatment are appropriately matched to the particular needs, 
preferences and wishes of each individual patient and their families)
 8.  Values-based practice is research-based, drawing in particular on the 
resources of philosophical value theory and a number of other areas of the philosophy of psychiatry, such as phenomenology, in addition to empirical 
social science methods, patient narratives and other sources
 9.  In clinical work, values-based practice is supported by a wide range of 
training materials and is the basis of a number of both national and 
international developments in psychiatry aimed at building a strong 
diagnostic and therapeutic alliance between professionals and patients in mental health and social care
10.  The skills-based approach of values-based practice is one of a number of

10.  The skills-based approach of values-based practice is one of a number of 
disciplinary resources for working with complex and conﬂ  icting values in 
medicine: in addition to ethics, other important disciplines include health economics and decision theory1.5.2 values and values-based practice in clinical psychiatry

SECTION 1  the subject matter of and approach to psychiatry 38
 9. Fulford, K.W.M., Dickenson, D. and Murray, T.H. (eds.) (2002) 
Healthcare Ethics and Human Values: An Introductory Text with Readings 
and Case Studies . Malden, USA, and Oxford, UK: Blackwell Publishers.
10. Hunink, M., Glasziou, P ., Siegel, J., et al. (2001). Decision Making in 
Health and Medicine: Integrating Evidence and Values . Cambridge: 
Cambridge University Press.
11. Brown, M. M., Brown, G.C. and Sharma, S. (2005). Evidence-Based 
to Value-Based Medicine . Chicago: American Medical Association 
Press.
12. Fulford, K.W.M. and Colombo, A. (2004). Six Models of Mental 
Disorder: A Study Combining Linguistic-Analytic and Empirical 
Methods.  Philosophy, Psychiatry, & Psychology, 11/2 , 129–44.
13. Stanghellini, G. (2004). Deanimated bodies and disembodied spirits. 
In Essays on the Psychopathology of Common Sense . Oxford: Oxford 
University Press.

14. Andreasen, N.C. (2001). Brave New Brain: Conquering Mental Illness in 
the Era of the Genome . Oxford: Oxford University Press.15. Kendell, R.E. (1975). The concept of disease and its implications for 
psychiatry. British Journal of Psychiatry ,127, 305–15.
16. Szasz, T.S. (1961; revised 1974). The Myth of Mental Illness .
Foundations of a Theory of Personal Conduct. New Y ork, USA: Harper and Row.
17. Sadler, J.Z. (2004). Values and Psychiatric Diagnosis . Oxford: Oxford 
18. Wakeﬁ  eld, J.C. (2000). Aristotle as Sociobiologist: The ‘Function of a 
Human Being’ Argument, Black Box Essentialism, and the Concept of Mental Disorder. Philosophy, Psychiatry, & Psychology, 7/1,
17–44.
19. Fulford, K.W.M. (1989, reprinted 1995 and 1999). Moral Theory and 

17–44.
20. Hare, R.M. (1952). The Language of Morals . Oxford: Oxford University 
Press.
21. Fulford, K.W.M., Thornton, T., and Graham, G. (2006). The Oxford 
Textbook of Philosophy and Psychiatry.  Oxford: Oxford University Press.

1.6
The psychiatrist as a manager
Introduction: integrating two perspectives
The past years have witnessed the introduction and implementa-
tion of strict macro and micro economical principles in the plan-ning and delivery of health care. The change is a consequence of the limitation of resources and the obligation to optimize their utilization in the delivery of health care to those in need. This has led to the birth of a new domain of management science dealing with hard choices and with the selection of priorities in the delivery of health care.
(1) Even Western European countries, where a tradi-
tion of equity presides over health care and developing countries, with a tradition of care based on welfare system are adopting strat-
egies built upon managed care principles. Of course, the private health care present in many forms in the different countries has been a driving force in this movement.

The new management perspective is based on the standards of 
management discipline but has to adapt to the main ethical concerns of delivery of care to suffering human beings. Because management has oftentimes been imposed as an ‘external’ mandate to the clinical community, clinicians, lacking understanding for the basics behind management, are reluctant to accept it; they often feel degraded by managers and develop negative attitudes towards them.
The objective of the present chapter is to provide clinicians with 
some input on how to manage the resources at hand and how to understand and communicate with managers in order to reach priorities closer to the needs of patients.
Health professionals and managers differ in many aspects. 
They belong to two different cultures which are summarized in 
Table 1.6.1.

However, many managerial skills are extremely useful to deal

However, many managerial skills are extremely useful to deal 
with psychiatric diseases, because they are chronic, they are accom-panied by high degrees of disability, they require an interdisciplin-ary perspective, and they have important interactions with the social environment. Nowadays, most psychiatrists work as mem-bers of a multidisciplinary team, need to develop collaborative working relationships with other professionals, should have an understanding of the roles and the limits and extent of involve-ment of other agencies, and lastly, of the lines of accountability. Furthermore, the concerns about the competence of psychiatrists that is the framework for training programmes include some such as: the psychiatrist is a medical expert, a communicator, a collaborator, a manager, a health promoter, a professional and somebody able to tolerate ambiguity and uncertainty. In most of those, managerial

skills are essential. Unfortunately, those skills are not taught in most medical schools.
There are three levels at which there is a parallel between a 
manager and a psychiatrist: a) the psychiatrist as a manager of the interventions needed to implement an individualized treat-ment plan for his patient, b) the psychiatrist as a manager of the involvement of other professionals in clinical settings, and c) the psychiatrist as a manager of health care resources available to his practice.
The psychiatrist as a manager of his patient’s needs is a conse-

quence of the introduction of processes of disease and patient management by most health care organizations. These play an increasing emphasis on prioritizing health care provision on the basis of limited resources and increased sensitivity to specialized patient needs. Therefore, the clinician has to keep a delicate balance between cost containment principles and quality in care provided. It is crucial for the psychiatrist to be able to identify and implement practices that assure quality of care without sacriﬁ  cing this to any 
external pressures for containment of cost within his clinical practice. 
The Madrid Declaration  of the World Psychiatric Association 
(WPA)
(2) has one item on the rights of psychiatrists that in essence 
Table 1.6.1  Two different cultures
Health professionals Managers
Values Health and ﬁ  ghting 
diseasesEconomy and 
administration
Main interest 1. Patients
2. The profession1. Organization

2. Management
Principal loyalty The profession The institutionMain concern Patients Health policyPersons are Patients Clients, stakeholdersTerminology Medical Business-likeTraining in management No YesClinical training Yes NoWorries about costs No YesStability in working places Long Short

SECTION 1  the subject matter of and approach to psychiatry 40
declares that the ﬁ  rst right of the psychiatrist is to be able to prac-
tice the profession without external constraints of any kind.
The psychiatrist as a manager of other professionals in clinical 
settings is consequently working as an element of a multidisci-plinary team. Everybody in a team should at least possess an under-standing of the essence, the extent and the limitations of cooperation and accountability. Managing other professional also largely refers to managing other psychiatrists within the same clinical settings. Management goes beyond the simple ‘coordination’ of various roles and steps in the process of providing health care, in the professional education of colleagues, the training of young professionals and the sharing of experience.
The psychiatrist as a manager of health care services has to

The psychiatrist as a manager of health care services has to 
struggle to reach a satisfactory degree of equity and in order to do so, the clinician has to become familiar with issues such as human resource management, customer satisfaction and change, crisis and conﬂ  ict management.
What is management?
The word management derives from the Italian maneggiare  ‘to 
handle’ (i.e., a horse), from mano  ‘hand’ , from Latin manus .
Management is ‘the art of getting things done through people’;(3) it 
is the act (sometimes the art) of conducting or supervizing some-thing (initially a business) and the thoughtful use of means to accomplish an end. Management needs to direct and to control a group of people or entities for the purpose of coordinating and harmonizing that group towards accomplishing a goal and it often encompasses the deployment and handling of human, ﬁ  nancial, 
technological, and other resources.
Management in health care is not new. Physicians have a long

Management in health care is not new. Physicians have a long 
tradition of being supervisors or conductors of a team. The simplest 
form of management is the partnership, an essential model for the doctor–patient relationship.
Management can also refer to the person or people who perform 
the acts of management; in this sense management has to do 
with power by position, whereas leadership involves power by 
inﬂ uence.
From a functional perspective, management consists of measur-
ing a quantity on a regular basis and of adjusting some initial plan in order to reach an intended goal. This applies even in situations where planning does not take place.
Functions of management
Management has several functions, which are summarized as following:
 Planning : deciding what needs to happen in the future and 
generating plans for action.
 Organizing : making optimum use of the resources required to 
enable the successful carrying out of plans.

Planning : deciding what needs to happen in the future and 
 Leading and motivating : exhibiting skills in these areas for 
getting others to play an effective part in achieving plans.
 Coordinating : making different people or equipments work 
together for a goal or effect.
 Controlling  (monitoring ): checking progress against plans, 
which may need modiﬁ  cation based on feedback.Basic managerial concepts
Although in the following paragraphs we will, as often as possible, 
replace managerial jargon by one more pleasant to clinicians, there some basic concepts which need a deﬁ  nition.
Efﬁ cacy  is the ability to produce a desired effect and it is mea-
sured by the closeness to an achievable goal.
In clinical settings, efﬁ  cacy is the degree of the beneﬁ  t for patients,

In clinical settings, efﬁ  cacy is the degree of the beneﬁ  t for patients, 
induced by an intervention (treatment, procedure or service) in ideal research conditions (i.e., in a controlled trial). It indicates that the therapeutic effect is acceptable. ‘Acceptable’ refers to a consen-sus that it is at least as good as other available interventions to which it will have ideally been compared to in a clinical trial.
Effectiveness , on the contrary, refers to the impact in real world 
situations.
Efﬁ ciency  is the achieved results or effects related to the effort 
invested in terms of money, time and other resources. It is the max-imization of some desired output or effect for the least amount of input, means or effort. Usually, the larger the ratio, the greater the efﬁ ciency.
Efﬁ ciency is not a pure scientiﬁ  c concept as it carries a value

Efﬁ ciency is not a pure scientiﬁ  c concept as it carries a value 
judgement. Efﬁ  ciency is achieved through design, the process by 
which intelligence is substituted for matter and energy in techno-logical systems. 
Productivity  is a measure of efﬁ  ciency; it is the amount of out-
put created (in terms of goods produced or services rendered) per unit input used. For instance, labour productivity is measured as output per worker or output per labour-hour.
Equity  is social justice, the way of providing services according 
to the needs of each individual in a deﬁ  ned population. It is not an 
equalitarian principle because each individual should not get the same, but what he or she would need in a speciﬁ  c situation.
The light bulb example: the efﬁ  cacy is the amount of visible light 
measured in lumens; the efﬁ  ciency is the ratio of lumens to the

measured in lumens; the efﬁ  ciency is the ratio of lumens to the 
amount of energy consumed to produce them, measured in Watts. Equity will measure the reach of the lumens to the needs of, let’s say, the passers by on a street.
Ethical aspects of management in 
clinical settings
Health care and economic management are two different cultures. 
Cultures are deﬁ  ned by their values and peculiarities, among them 
ethics. Speciﬁ  c values are part of the property of a culture and 
belong to the identity of every social group.
There are three stages in the development of medical ethics,(4)
each one adding value to the previous one without replacing it totally. In each one of them particular managerial skills are helpful.
The ethics of welfare  is the traditional medical ethics, ﬁ  rst

The ethics of welfare  is the traditional medical ethics, ﬁ  rst 
appeared in Hippocratic writings. According to it, the doctor’s primary goal and duty are the well-being of the patient and as much as possible, harm avoidance. The doctor is perceived and behaves as a good father, to be fully trusted, convinced that the physician will act adequately to the beneﬁ  t of the patient. T o meet 
this obligation, the doctor has to increase to the maximum his own medical knowledge and to assume a series of obligations. The scientiﬁ  c advances increase the paternalism of the professional who 
has to learn how to manage information. The Madrid Declaration

41
of the WPA expressed this notion in the following way: Psychiatry 
is a medical discipline concerned with the provision of the best treat-ment for mental disorders. Psychiatrists serve patients by providing the best therapy available consistent with accepted scientiﬁ  c knowl-edge and ethical principles. It is the duty of psychiatrists to keep abreast scientiﬁ  c developments of the specialty.
The USA inﬂ  uence, with its strong emphasis on autonomy and 
individualism, has lead to the ethics of autonomy . The ethics of

individualism, has lead to the ethics of autonomy . The ethics of 
autonomy considers the patient as an autonomous human being, adult and free and consequently, able to take his/her own decisions. The values and beliefs of the patient are the background for the moral responsibilities of the doctor. As a consequence, doctors have to truly inform patients about all possible diagnoses and treatments so that patients are able to decide. The basic element of this new way of establishing the doctor-patient relationship is the informed consent.
(5) From this perspective, patient-doctor relationship is 
deﬁ ned in new terms: The patient should be accepted as a partner by

deﬁ ned in new terms: The patient should be accepted as a partner by 
right in therapeutic process. The therapist-patient relationship must be based on mutual trust and respect to allow the patient to make free and informed decisions. It is the duty of psychiatrists to provide the patient with relevant information so as to empower the patient to come to a rational decision according to his or her personal values and preferences  (WPA Madrid Declaration ).
The ethics of equity  is a consequence of the impact of economic 
factors in medicine. The need of equal access to health care resources for all patients, including those suffering from mental illnesses and the principle of equity in a period of intrinsic and extrinsic limita-tions to health care cost, is leading to a third stage of bioethics which has also been called the ethics of management . The main 
reasons for the increase or imbalance of the costs are partially due

reasons for the increase or imbalance of the costs are partially due 
to the successful developments of modern medicine: health care by itself is increasingly expensive (implementation of new and expen-sive technologies, incorporation of new professions into medicine, ﬁ nancing research in biomedical sciences, and applying resources 
for the training of physicians and specialists); the better control of acute diseases which increases the proportion of chronic illness requiring care; the increased demand due to ageing of the popula-tion and in social security systems, the change in the population pyramid, decreases the population of those paying compared to those making the expenses.
Resources to be invested in health care are limited. The ﬁ  rst one 
to ask for limits was President Carter in the USA, during his ﬁ  rst

to ask for limits was President Carter in the USA, during his ﬁ  rst 
public speech after assuming the presidency, when he claimed for a ceiling of the 7 per cent of the GNP to be devoted to health care. This was in 1977. But, why such a limit? Why could it not be possible for an enlightened society to decide to devote 10, 20 or even 50 per cent of its GNP to health care and less, for instance, to defence? President Carter expressed it very well: too much spend-ing in this area would decrease investments in education and care of the environment, which would lead to a deterioration of health.
(8) In Europe, the cost of brain disorders (to be precise brain 
diseases and mental disorders) is more than the double of the cost 
of all cancers and diabetes together.(7)
The fact that more is not better is evident when comparing health

The fact that more is not better is evident when comparing health 
indexes, and among them the bottom line, which is life expectancy. This is much lower in the US which dedicate over twice the per-centage of their GNP to health care, than countries such as Japan, France, Italy, or Spain.Economic factors can limit the access to health care, either 
because individuals lack sufﬁ  cient insurance coverage or because 
of waiting lists. In the last few years, limitations have been imposed by governments which through different approaches try to control the access of patients to interventions which are not considered economically worthy. Again the WPA has addressed these issues in several documents such as the Hawaii Declaration  (rev.), the 
WPA Statement and Viewpoints on the Rights and Legal Safeguards of the Mentally Ill , the ﬁ  rst ofﬁ  cial document on the rights of men-

tally ill, and the Madrid Declaration  of the WPA. This last code of 
ethics states ‘As members of society, psychiatrists must advocate for 
fair and equal treatment of the mentally ill, for social justice and equity for all. While doing so, psychiatrists should be aware of and concerned 
with the equitable allocation of health resources’.
Therefore, the goal of cost control should not be considered in

Therefore, the goal of cost control should not be considered in 
isolation from other goals, such as quality assurance and equity. Here a managerial approach is useful, when based on three pillars: Information (to know what we physicians do, how patients behave on long-term outcome of medical interventions and on the impact on quality of life), consensus (on the right approaches to decide interventions), and a new social contract on sustainable health care. This approach is not limited to health care, it has a great inﬂ  uence on the culture of modern enterprises and in post-
modern perspectives.
(9,10)
Nature of managerial activity

(9,10)
Nature of managerial activity 
Workplace democracy has become more common and advocated. Management is based on classical military type of command-and-control but it should not throw itself to the other extreme here all management functions are distributed among all workers, each of whom takes on a portion of the work, and the institution is run by assemblies of staff and of patients as was common in some anti-psychiatry experiences. Management relies increasingly more on facilitating, promoting and supporting collaborative activity, which is essential in health care. Modern management embraces democratic principles, in that, in the long term, workers must give majority support to management; otherwise they leave to ﬁ  nd 
other work, or go on strike.
In for-proﬁ  t organizations, the primary function of management 
is the satisfaction of a range of stakeholders. This typically means making proﬁ  t (for the shareholders), creating valued products

is the satisfaction of a range of stakeholders. This typically means making proﬁ  t (for the shareholders), creating valued products 
at a reasonable cost (for customers), and providing rewarding employment opportunities (for employees). In non-proﬁ  t man-
agement, other functions are added, such as keeping the faith of donors, attaining social and political goals such as increasing health and ﬁ  ghting diseases.
In most models of management, shareholders vote for the board 
of directors, and the board then appoints senior management. This model is rarely applied in health care (or in Academic life).
Management also has the task of innovating and improving the 
functioning of organizations.
Categories of management
There are many categories of management. The most important are: human resource management, production (operations) man-agement, strategic management, marketing management, ﬁ  nancial

There are many categories of management. The most important are: human resource management, production (operations) man-agement, strategic management, marketing management, ﬁ  nancial 
management, and information technology management. 1.6 the psychiatrist as a manager

SECTION 1  the subject matter of and approach to psychiatry 42
Nevertheless, as more and more processes simultaneously involve 
several categories, it is better to think in terms of the various pro-cesses, tasks, and objects subject to management.
Management science and organizational 
psychology
Whether management is rightly claiming a scientiﬁ  c status is 
debatable. It is more appropriate to classify it as a branch of eco-nomic sciences often confounded with its practical arm, operations research. Management science is the discipline of using analytical methods, to help make better decisions. Among others methods are decision-making analysis, optimization, simulation, forecasting, game theory
(11) (which had a strong impact in psychotherapy(12)), 
network (transportation) forecasting models, mathematical modelling, data mining, probability and statistics, morphological analysis, resources allocation, and project management.

Industrial and organizational psychology consists of the applica-
tion of psychological theories, research methods, and intervention strategies to workplace issues in order to hire suitable employees for the job, to reduce absenteeism, to improve communication and to increase job satisfaction.
Information systems 
An information system is the array of persons, data records and activi-ties that process the data and information in a given organization, including manual processes or automated processes. Information systems are also social systems whose behaviour is heavily inﬂ  uenced 
by the goals, values and beliefs of individuals and groups, as well as the performance of the technology. An information system consists of three components: human, technology, and organization.
(13)

(13)
The systems rely on data from the unit as well as data acquired 
outside it (such as literature research, scientiﬁ  c meetings, consen-
sus documents and others) and data provided by others (i.e. the Health Care System, partners, suppliers, and customers).
A computer based information system is a technologically 
implemented medium for recording, storing, and disseminating linguistic expressions, as well as for drawing conclusions from such expressions.
(14)
Managerial levels and styles
The management of a large organization usually has three self-evident levels: senior management, middle management, and low-level management.
There are several management styles that can be applied depend-

ing on the nature of the activity, the type of the task, the character-istics of the workforce, and the personality and skills of the leaders. As the style of leadership is dependent upon the prevailing circum-stance, leaders should exercise a range of leadership styles and should deploy them as appropriate.
(15)
An autocratic  or authoritarian manager makes all the decisions 
and keeps the information and decision-making among the senior management. Objectives and tasks are set and the workforce is expected to do exactly as required. The communication involved with this method is mainly downward, from the leader to the subor-dinate. The main advantage of this style is that the direction of the business is stable and the decisions are similar and comparable. This in turn projects the image of a trustworthy and well managed business. However, this method can lead to a decrease in motivation

of employees and subordinates who may become highly dependant 
on the leaders and close supervision may be unavoidable.
Apaternalistic  approach is also dictatorial; however, the deci-
sions tend to be in the best interests of the employees rather than 
the business. This can help balance out the lack of worker motiva-tion caused by an autocratic management style. Feedback is again generally downward; however, feedback to the management will occur in order for the employees to be kept happy. This style can be highly advantageous, and can engender loyalty from the employ-ees, leading to a lower labour turnover, thanks to the emphasis on social needs. It shares the same disadvantages of the authoritarian style; employees becoming highly dependant on the leader, and if 
wrong decisions are made, then employees may become dissatisﬁ  ed 
with the leader.
In a democratic  style, the manager allows the employees to take

In a democratic  style, the manager allows the employees to take 
part in decision-making; therefore everything is agreed by the majority. The communication is extensive in both directions (from subordinates to leaders and vice-versa). This style can be particu-larly useful when complex decisions that require a range of special-ized skills need to be made. From the overall business point of view, job satisfaction and quality of work will improve. However, the decision-making process is severely slowed down, and the need of a consensus may avoid taking the ‘best’ decision for the business. It can go against a better choice of action.
In a laissez-faire  leadership style, the leader’s role is peripheral

In a laissez-faire  leadership style, the leader’s role is peripheral 
and the staffs manage their own areas of the business; the leader therefore evades the duties of management leading to an uncoordi-nated delegation. The communication in this style is horizontal, meaning that it is equal in both directions; however, very little communication occurs in comparison with other styles. The style brings out the best in highly professional and creative groups of employees; however, in many cases it is not deliberate and is simply a result of poor management. This leads to a lack of staff focus and sense of direction, which in turn leads to much dissatisfaction, and a poor company image.
Roles and responsibilities of heads of clinical 
units and leaders
The head of a clinical unit is a managing director. In business, 
the principal leader is the Managing Director, who is in charge of the deﬁ  nition, the development and implementation of the strate-

gic plan of their unit or service in the most cost-effective and time-efﬁ cient manner.
The managing director is responsible for both the day-to-day 
running of the company and developing business plans for the long-term future of the organization. In business, the managing director is accountable to the board and the shareholders of the company. It is the board that grants the managing director the authority to run the company. In clinical settings, the head of a unit is accountable to and gets the power from the health authorities.
A head of a unit may or may not have direct clinical responsibili-
ties and is usually burdened by much ofﬁ  ce-based work, but he or 
she is the leader of the organization, chairing different sorts of

she is the leader of the organization, chairing different sorts of 
meetings, motivating the workforce and developing the culture and style of the organization.
As the title suggests, the managing director needs to manage 
everything. This includes the staff, the patients, the budget and the

43
resources to make the best use of them and increase the company’s 
proﬁ tability.
Strategic planning
Strategic planning is the process of deﬁ  ning the goal of an organi-
zation and of making decisions on allocating resources to pursue the goal. In order to determine where it is going, the organization needs to know exactly where it stands, then determine where it wants to go (over the next years, typically 3 to 5) and how it will get there.
(16) The resulting document is called the ‘strategic plan’ .
Strategic planning deals with at least one of three key questions: 
1 ‘What do we do?’ 2. ‘For whom do we do it?’ and 3. ‘How do we excel?’
There are many approaches to strategic planning. Typically it is 
done in a stepwise manner:
1 Vision (deﬁ  ne the vision and set a mission statement with a 
hierarchy of goals);
2 SWOT analysis (strengths, weaknesses, opportunities and 
threats);
3 Formulation (of the actions and processes to be taken to attain 
these goals);

threats);
4 Implementation (of the agreed upon processes);
5 Controlling (to get full control of the operation); and
6 Monitoring (to get feedback from implemented processes).
(17)
Situational analysis . When developing strategies it is important 
to analyze the organization and its environment in the present moment and how it may develop in the future. The analysis has to be executed both at internal as well as at external levels to identify all opportunities and threats of the new strategy. Analysis of the external environment normally focuses on the customer (the needs of patients).
Goals, objectives and targets: Vision, mission and values.  These 
are essential components of strategic planning. They are speciﬁ  c,

are essential components of strategic planning. They are speciﬁ  c, 
time-bound statements of intended future results, and general and continuing statements of intended future results.
AVision statement  outlines what a clinical unit wants to be in 
the future; it is a source of inspiration and provides clear decision-making criteria. It reﬂ  ects the optimistic, perhaps utopic view of 
the organization’s future.
AMission statement  describes what the unit or service is at 
present. It deﬁ  nes the customers (kinds of patients), critical pro-
cesses and it informs about the desired level of performance.
A vision statement is different from a mission statement. The 
Vision describes a future identity and the Mission describes why it will be achieved.
AV alues statement  describes the main values protected by the 
organization during the progression, reﬂ  ecting the organization’s 
culture and priorities.

Management by objectives
Management by Objectives (MBO)(18) is a method of agreeing on 
objectives within an organization. The management and the head of clinical units reach a consensus on the objectives to attain in a certain time period (typically one year). The objectives have to comply with some criteria, usually described by the acronym SMART (Speciﬁ  c, Measurable, Achievable, Realistic, and Time-
Speciﬁ  c). They usually represent an increased level of performance

Speciﬁ  c). They usually represent an increased level of performance 
than the one attained during the previous period of time. The objectives of each clinical unit are part of the global objectives of the hospital or the higher level organization (i.e., the health care area) which are the result of the consensus between the organiza-tion and the health care authorities. Some objectives are collective, while others can be individualized. Ideally, the responsible of a clinical unit shares and divides the objectives among the respon-sible staff under his authority.
(19)
The achievement (or non-achievement) of the objectives should 
lead to incentives (or penalties). In health care, signiﬁ  cant pay 
incentives (bonuses) are not common, and this is an advantage because high bonuses trigger unethical behaviour such as distort-ing ﬁ  nancial ﬁ  gures to achieve short term individual targets. This is 
the main criticism of management by objectives.
Quality management

Quality management is an exceptionally useful tool for the running of clinical services. It is based on scientiﬁ  c excellence which includes 
research on efﬁ  cacy and efﬁ  ciency. In can include systems to con-
trol costs but accompanied by methods to sustain and increase quality. The basic assumption is that cost control and quality of care can run in parallel. Of the several approaches, we have chosen for this chapter, the European Foundation for Quality Management (EFQM)
(20) model, because it is increasingly been used by health 
care administration in many countries and not only by Europeans, and although developed for the management of very large companies it soon became evidence of their advantages for the public sector.
The EFQM model relies on the strive over Excellence, which is 
deﬁ ned as the outstanding practice in managing the organization

deﬁ ned as the outstanding practice in managing the organization 
and achieving results . Truly Excellent organizations are those that 
strive to satisfy their stakeholders by what they achieve, how they achieve it, what they are likely to achieve, and the conﬁ  dence 
they have that the results will be sustained in the future. Being excellent requires total leadership commitment and acceptance of the fundamental concepts, a set of principles on which the organization bases its behaviours, activities, and initiatives.
Excellence relies on a few fundamental concepts (Fig. 1.6.1):
1 Results Orientation: Excellence is achieving results that delight 
all the organization’s stakeholders.
2 Customer Focus: Excellence is creating sustainable customer 
(patient) value.
3 Leadership and Constancy of Purpose: Excellence is visionary and 
inspirational leadership, coupled with constancy of purpose.

4 Management by Processes and Facts: Excellence is managing the 
organization through a set of interdependant and interrelated systems, processes and facts.
5 People Development and Involvement: Excellence is maximizing 
the contribution of employees through their development and involvement.
6 Continuous Learning, Innovation and Improvement: Excellence 
is challenging the status quo and effecting change by utilizing learning to create innovation and improvement opportunities.
7 Partnership Development: Excellence is developing and main-
taining value-adding partnerships.1.6 the psychiatrist as a manager

SECTION 1  the subject matter of and approach to psychiatry 44
8 Corporate Social Responsibility: Excellence is exceeding 
the minimum regulatory framework in which the organization operates and strives to understand and respond to the expecta-tions of their stakeholders in society.
The EFQM Excellence Model is a practical tool that can be used 
in a number of different ways: as a tool for self-assessment; as a way to benchmark with other organizations; as a guide to identify areas for improvement; as the basis for a common vocabulary and a way of thinking; as a structure for the organization’s management system.
The EFQM Excellence Model is a non-prescriptive framework 
based on nine criteria (Fig. 1.6.2). Five of these are ‘Enablers’ and four are ‘Results’ . The ‘Enabler’ criteria covers what an organization does. The ‘Results’ criteria covers what an organization achieves. ‘Results’ are caused by ‘Enablers’ and ‘Enablers’ are improved using feedback from ‘Results’ .
Risk management

Risk management is a discipline for living with the possibility that future events may cause adverse effects. The term is increasingly been used in the health sector.
Risk analysis  includes risk assessment (identifying sources of 
potential harm, assessing the likelihood that harm will occur and the consequences if harm does occur), risk management (evalua-tion of the risks identiﬁ  ed that require action and selection and 
implementation of the procedures to control those risks), and risk communication (interactive dialogue between all parties involved in the risk).
There are seven principles in the management of risk:
1 Global perspective (recognizing both the potential value of 
opportunities and the potential impact of adverse effects);
2 Forward-looking view (identifying uncertainties, anticipating 
potential outcomes);
3 Open communication (encouraging free-ﬂ  owing information at 
and between all levels);

4 Integrated management (risk management is an integral part of 
management);
5 Continuity (maintaining constant vigilance);
6 Shared vision (common purpose, collective communication, and 
focusing on results); and
7 T eamwork (pooling talents, skills, and knowledge).The experience of psychiatrists in disaster and traumatic events 
has made them highly valuable experts in risk management.
Types of health care and management 
systems
Health Systems throughout the world share the same, although 
sometime distant, goals: accessibility, equity, and extensive range of coverage. But there is also a wide array of organizational and ﬁ  nanc-
ing types (taxation, employer-employee based private insurance, mixed), which have a strong impact on their efﬁ  ciency, effectiveness,

ing types (taxation, employer-employee based private insurance, mixed), which have a strong impact on their efﬁ  ciency, effectiveness, 
equity, and productivity. On the basis of ﬁ  nancial policy, the follow-
ing three main health care systems can be distinguished:
1 The social insurance system: It is also known as Bismarck model. 
It is based on obligatory insurance funded by both the employer and the employees. It guarantees collectivity, bilateral consent, and social solidarity. There is only marginal interference by the state, which however, is the main provider of health care facili-ties. Patients are free to choose their primary care physician, who is either a free professional or salaried to an insurance agency. In some countries, this system has evolved into the next one.
2 Government-state controlled through taxation system:

2 Government-state controlled through taxation system: 
Introduced by Beveridge in the U.K., it guarantees free of charge access of all citizens to health care services. Planning, program-ming, ﬁ  nancing, and administration of services, as well as pre-
vention and public health policy are centrally controlled. The system is ﬁ  nanced through taxes as health care is considered 
a right of the citizens. Interestingly enough, it often co-exists with a non-negligible private insurance sector, which offers reduced waiting lists, better accommodation facilities, a more free election of the doctors and other privileges. In both cases, there are some limitations to access such as, having the primary care physician as the ﬁ  rst contact and gate-keeper.
3 The private health system: The system is financed either

3 The private health system: The system is financed either 
through private insurance or by direct (out of the pocket) pay-ment by the patient. Population insurance is not obligatory. Both, the patients and the physicians preserve the right of choice and payment is based on fee per service. The private system ﬂ ourishes in the USA where about 2/3 of Health Services belong Fig. 1.6.1 Concepts of excellence.Results orientation
Customer focus
Leadership and
constancy of purpose 
Management by processes
and facts 
People development and involvementContinuous learning, improvement
and innovationPartnership developmentPublic responsibility
Fig. 1.6.2 European Foundation for Quality Management.LeadershipPersons
Policy
and
strategy
Alliances
and
resourcesResults on
persons
Key
resultsResults on
clients
Results on
the society ProcessesEnablers Results
Innovation and learning

45
to private or to managed care for proﬁ  t or non-proﬁ  t organiza-
tions. Governmental contribution to health care free of charge for patients is limited to the uninsured, very poor, and elderly as well as to patients in emergency through the Medicare and Medicaid Federal Government programs.
The more recent trend is towards adopting a mixed system of 
ﬁ nancing of health services, with an increasing collaboration of 
the private sector both in ﬁ  nancing the services and in providing 
medical care.
Managed care

Managed care is the use of business managerial principles, strate-gies and techniques in health care. As it started in the USA during the presidency of Ronald Reagan, in a restricted sense is only applied to this country as a way to control Medicare and Health Maintenance Organizations’ (HMO’s) payouts. However, nowa-days every system including those more controlled by governments use the same approach to control costs. Governmental run systems are just big nationwide HMO’s and confront clinicians with the same restrictions to their work, patients with limitations of access, be it only waiting lists, conﬂ  icts of interests and confrontation of 
cultures. Essentially, it is a reform of health care from its longstand-ing not-for-proﬁ  t business principles into a for-proﬁ  t model that

cultures. Essentially, it is a reform of health care from its longstand-ing not-for-proﬁ  t business principles into a for-proﬁ  t model that 
would be driven by the insurance industry or governmental bodies ruled by the same principles.
The reason for the beginning of managed care is the need to 
control cost and to reduce the so-called medical inﬂ  ation which in 
the 1980s and 90s, was running at twice or thrice the general inﬂ  ation 
rate. Nevertheless, managed care has not been so successful at this role, but has brought rationality in the use of public resources in health care, and often into attracting private resources to a success-ful for-proﬁ  t business model.
There are several forms of managed care. Plans range from more 
restrictive to less restrictive, and include:
Health Maintenance Organization (HMO)

An HMO is an insurance plan under which an insurance company gears most aspects of the health care of the insured person. Each insured person is assigned a ‘gatekeeper’ , usually a primary care physician who is responsible for the overall care of members assigned to him/her. Specialty services require a speciﬁ  c referral 
from the primary care physician to the specialist. Non-emergency hospital admissions also require speciﬁ  c pre-authorization by the 
PCP . Typically, services are not covered if performed by a provider not an employee of or speciﬁ  cally approved by the HMO, unless it 
is an emergency as deﬁ  ned by the HMO. The HMO concept was 
introduced in 1960 by Dr. Paul Elwood
(21) and was adopted by the 
Nixon Administration.
Preferred Provider Organization (PPO)

PPO is a coinsurance system, which provides patients a co payment (generally around 80 per cent) of the costs of care, for an insurance 
fee. The deductible is the ﬁ  rst part of the coverage and is paid 
by the patient. After the deductible is met, the coinsurance portion applies. Because the patient is picking up a substantial portion of the ‘ﬁ  rst dollars’ of coverage, PPO is the least expensive type 
of coverage.Point of Service (POS)
A POS plan utilizes some of the features of each of the above plans. Members of a POS plan do not make a choice about which system to use until the point at which the serv ice is being used. For example,

if the patient stays in a network of providers and seeks a referral to use a specialist, they may have a co payment only. However, if they use a network provider, but do not seek a referral, they will pay more.
It is clear that the modern role of both the physicians, in general, and psychiatrists, in particular, requires intensive decision-making which is helped by management principles.
Psychiatrists, in addition to their clinical qualiﬁ  cations and skills 
are asked to occupy positions and undertake responsibilities as clinical executives, directors of health care facilities, administrators of Academic units and even Mental Health Commissioners, all of them requiring managerial knowledge and leadership qualities.
Increased pressure by patients for improved quality of services

Increased pressure by patients for improved quality of services 
and access to new and innovative treatments needs to be balanced against the expectation of the health care system of the physician to act ‘economically’ , following cost containment guidelines and staying within expenditure ceilings.
Such decisions require specialized knowledge and a deep under-
standing of the principles and the functions of management and

standing of the principles and the functions of management and 
health economics. Such knowledge is only gained through special-ized training by introducing management teaching, either at the undergraduate level or preferably at the residency level, as part of the core curriculum or as an elective which may include items such as administration principles, quality assurance, budgeting, resource allocation, accreditation procedures and what is close to the psy-chiatrist’s clinical background the personnel management. This may be extended to ongoing professional education programmes for psychiatrists who are already active in the ﬁ  eld.
Harvard Business Review http://harvardbusinessonline.hbsp.harvard.edu
World Psychiatric Association Section on Mental Health Economics Prof.

World Psychiatric Association Section on Mental Health Economics Prof. 
Katarzyna Prot, Chair Institute of Psychiatry & Neurology. IV Dept. of Psychiatry Ceglowska 80. Warsaw, Poland 01-809 T: (40-21) 230-0653; 
F: (40-21) 230-7832 prot@bukareszt.ro; http://www.wpanet.org
1. Porter, M.E. and T eisberg, E.O. (2006). Redeﬁ  ning Health Care: Creating 
Value-Based Competition on Results . Harvard Business School Press, 
Boston.
2. World Psychiatric Association (1998). The Madrid Declaration. Current 
Opinion in Psychiatry ,11, 1.
3. Follett, M. P . (1951). Creative Experience . Peter Smith, New Y ork.
4. López-Ibor, J.J. and Crespo Hervás, M.D. (2000). A West Mediterranean 
Perspective. In Ethics, Culture and Psychiatry. International Perspectives .
(eds. A. Okasha, J. Arboleda-Florez, and N. Sartorius). American Psychiatric Press, Inc. Washington, DC.

5. López-Ibor, J.J. and Crespo Hervás, M.D. (1996). Informed Consent in 
Spain. In Informed Consent in Psychiatry. European Perspectives 
of Ethics, Law and Clinical Practice . (eds. H.G. Koch, S. Reiter-Theil, 
and H. Helmchen), pp. 233–7. Medizin in Recht und Ethik, Band 33, 
Nomos, Baden-Baden.1.6 the psychiatrist as a manager

SECTION 1  the subject matter of and approach to psychiatry 46
 6. López-Ibor, J.J. (1997). Psychiatric Care under the Present Economic Era. 
An International Perspective. European Psychiatry ,12 (suppl 2), 
88–91.
 7. Andlin-Sobocki, P ., Jonsson, B., Wittchen, H.U., et al. (2005). Cost of 
disorders of the Brain in Europe. European Journal of Neurology ,
Jun. 12 (suppl 1), 1–27.
 8. World Psychiatric Association (1990). The WPA Bulletin  VI N.2–3.
 9. Naisbitt, J. (1982). Megatrends: Ten New Directions Transforming our 
Lives . Macdonald.
10. Callahan, P . (1991). What kind of Life . Simon & Schuster, New Y ork.
11. Morgenstern, O. and von Neumann, J. (1947). The Theory of Games and 
Economic Behavior . Princeton University Press 
12. Berne, E. (1964). Games People Play – The Basic Hand Book of 
Transactional Analysis . New Y ork: Ballantine Books.
13. Angell, I.O. and Smithson, S. (1991). Information Systems Management:

13. Angell, I.O. and Smithson, S. (1991). Information Systems Management: 
Opportunities and Risks . Macmillan, London.14. Langefors B. (1973). Theoretical Analysis of Information Systems .
Philadelphia, Auerbach Publishers.
15. Tannenbaum, R.and Schmidt, W.H. (1985). How to Choose a 
Leadership Pattern. Harvard Bussines Review , March–April, 
95–101.
16. Bradford, R.W., Duncan, P . and Tarcy, B. (2000). Simpliﬁ  ed Strategic 
Planning . Chandler House Press, Worcester, MA. 
17. Fahe, L. and Narayanan, V .K. (1986). Macroenvironmental Analysis 
for Strategic Management . West Publishing Company, 
New York. 
18. Drucker, P . (1964). Managemet for Results . Harper & Row, New Y ork.
19. Goldratt, E.M. and Cox, J. (2004). The Goal: A Process of Ongoing 
Improvement . North River Press, Great Barrington, MA.

20. http:// www.efqm.org21. Ellwood, P .M. Jr., Anderson, N.N., Billings, J.E., et al. (1971). Health 
maintenance strategy. Medical Care ,9(3), 291–8.

1.7
Descriptive phenomenology
Principles of descriptive phenomenology
Deﬁ nitions and explanations
Psychopathology is the systematic study of abnormal experience, 
cognition, and behaviour. It includes the explanatory psychopa-
thologies , where there are assumed causative factors according 
to theoretical constructs, and descriptive psychopathology , which 
precisely describes and categorizes abnormal experiences as recounted by the patient and observed in his behaviour.
(1) Therefore 
the two components of descriptive psychopathology are the obser-vation of behaviour and the empathic assessment of subjective experience. The latter is referred to by Jaspers as phenomenology ,
(2)
and implies that the patient is able to introspect and describe what

(2)
and implies that the patient is able to introspect and describe what 
these internal experiences are, and the doctor responds by recog-nizing and understanding this description. Descriptive phenome-nology, as described here, is synonymous with pheno menological psychopathology, and involves the observation and categorization of abnormal psychological events, the internal experiences of the patient, and consequent behaviour. The attempt is made to observe and understand this psychological event or phenomenon  so that 
the observer can, as far as possible, know what the patient’s experi-ence must feel like.
Mental phenomena in health and cultural variation
It is not surprising that the identiﬁ  cation and classiﬁ  cation of 
the phenomena of mental illness is a difﬁ  cult task as there is no

the phenomena of mental illness is a difﬁ  cult task as there is no 
consensus concerning what would be acceptable as normal healthy experiences. Mental illness has variously been considered as the products of a diseased brain, the symptoms that doctors treat, or a statistical variation from the norm carrying biological disadvan-tage, and mental illness often has legal implications. It is best to retain the use of the word ‘normal’ in a statistical sense; thus a phenomenon, such as hypnagogic hallucination, may be statisti-cally abnormal but not an indicator of ill health or mental disease. Similarly, it is unwise to extrapolate from a population of mentally ill people and make assertions about the origins of behaviour in 
those who are not mentally ill.
It is important to recognize the effect of culture  on subjective

It is important to recognize the effect of culture  on subjective 
experience, the expression of psychological symptoms, and their manifestation in behaviour. In some cultures the very expression of subjective experience and emotion is discouraged and censored, in others feelings tend to be somatized, and in yet others the 
subjective experience of the individual tends to be subjugated to the sense of well being of the immediate social group. There are speciﬁ  c culture-bound expressions of subjective distress concern-

ing body image in those who suffer from anxiety disorders. For delusions of passivity, although the psychopathological form remains relatively constant, the description of content will vary according to culture; for example, ‘the djinn made me do it’ , ‘my thoughts are controlled by the television’ . Similarly, for possession state, although the psychopathological description remains similar, the actual cultural expression is very different between a member of a fundamentalist sect in the American Appalachian Mountains and a Buddhist girl in Sri Lanka.
Understanding the patient’s symptoms
Although in internal medicine a clear distinction is made between symptom  (the complaint which the patient makes) and sign  (the 
indicator of speciﬁ  c disease observed or elicited on examination),

indicator of speciﬁ  c disease observed or elicited on examination), 
in psychiatry both are contained within the speech of the patient. He complains about his unpleasant mood state, therefore identify-ing the symptom ; he ascribes the cause of the pain in his knee to 
alien forces outside himself, thus revealing a sign of psychotic ill-
ness. Because both symptoms and signs emanate from the patient’s conversation, in psychiatric practice the term symptom is often used to include both. For a symptom to be used diagnostically, its occurrence must be typical of that condition and it must occur relatively frequently.
Fundamental to psychiatric examination is the use of empathic
understanding  to explore and clarify the patient’s subjective 
experiences. The method of empathy implies using the ability

experiences. The method of empathy implies using the ability 
to ‘feel oneself into’ the situation of the other by proceeding through an organized series of questions, rephrasing, and reiterat-ing where necessary until one is quite sure of what is being described by the patient. The ﬁ  nal stage is recounting back to the patient 
what you, the psychiatrist, believe the patient’s experience to be, and the patient recognizing that as indeed an accurate representa-tion of their own internal state. Empathy uses the psychiatrist’s capacity, as a fellow human being, to experience what the patient’s subjective state must feel like as it arises from a combi-nation of external environmental and internal personal circumstances.

SECTION 1  the subject matter of and approach to psychiatry 48
Identifying phenomena as speciﬁ  c indicators of deﬁ  ned psycho-
pathology may be difﬁ  cult. It may require hearing much conversa-
tion from the patient for signiﬁ  cant words and sentences to be 
revealed. The psychiatrist, when in the role of psychopathologist, has to assume that all speech of the patient, all behaviour of the patient, and every nuance has meaning, at least to the patient at the time the speech or behaviour takes place; it is not just an epiphe-nomenon of brain functioning.
Jaspers has contrasted understanding  with explaining ; descrip-

tive phenomenology is concerned with the former. Understanding is the perception of personal meaning of the patient’s subjective experience and involves the human capacity for empathy. That is, I understand because I am able to put myself into my patient’s situation and know for myself how he is feeling, I feel those feelings of misery myself. Explanation is concerned with observation from outside and working out causal connections as in scientiﬁ  c method. 
In psychopathology, the terms primary  and secondary  are based

In psychopathology, the terms primary  and secondary  are based 
upon this important distinction between meaningful and causal connections. That which is primary can be reduced no further by understanding, i.e. by empathy. What is secondary emerges from the primary in a way which can be understood by putting oneself into the patient’s situation at the time; that is, if I were as pro-foundly depressed as my patient, I could have such a bleak feeling that I believed the world had come to an end—a nihilistic second-ary delusion.
Subjective experience and its categorization
Within certain limits subjective experience is both predictive and quantiﬁ  able. When an individual loses a close relative it can be

Within certain limits subjective experience is both predictive and quantiﬁ  able. When an individual loses a close relative it can be 
predicted that he or she will experience misery and loss. It is possi-ble to quantify depressive symptoms and compare the degree of depression at different times in the same individual or differences between individuals at the same time. An important distinction for psychopathology is that between form and content. The form
of psychological experience is the description of its structure in phenomenological terms (e.g. a delusion). Its content  is the psy-
chosocial environmental context within which the patient describes this abnormal form: ‘Nurses are coming into the house and stealing my money’ . The form is dependent upon the nature of the mental illness, and ultimately upon whatever are the aetiological factors of that condition. Content is dependent upon the life situation,

culture, and society within which the patient exists. The distinction 
is important for diagnosis and treatment; determining the psycho-pathological form is necessary for accurate diagnosis, whereas demonstrating the patient’s current signiﬁ  cant concerns from the 
content of symptoms will be helpful in constructing a well-directed treatment regime.
Whereas most science is concerned with objectivity and with 
trying to eliminate the observer as far as possible from being a vari-able within the experiment, descriptive phenomenology tries to make evaluation of the subjective both quantiﬁ  able and scientiﬁ  c.

It is a mistake to discredit subjectivity in our clinical practice. Inevitably we use it all the time and we should learn to use it skil-fully and reliably. When I make an assessment that my patient is depressed, I am, at least to some extent, making a subjective judge-ment based upon the experienced and disciplined use of empathy: ‘If I felt as my patient looks and describes himself to be, I would be feeling sad’ . In psychopathology the distinction is also made between development , where a change of thinking or behaviour can be seen as emerging from previous patterns by understanding 
what the individual’s subjective experience is, and process , where

what the individual’s subjective experience is, and process , where 
an event is imposed from outside and this cannot be understood in terms of a natural progression from the previous state. Anxiety symptoms could be seen as a development in a person with anan-kastic personality confronted with entirely new external circum-stances; epilepsy and its psychiatric symptoms would be a process imposed upon the individual and not understandable in terms of previous life history.
Theoretical bases of descriptive phenomenology
There are important theoretical differences from dynamic psycho-pathology. Descriptive psychopathology does not propose explanations accounting for subjective experience or behaviour, but simply observes and describes them. Psychoanalytic psychopa-thology studies the roots of current behaviour and conscious experience through postulated unconscious conﬂ  icts and under-

stands abnormalities in terms of previously described theoretical processes. The distinction between form and content and between process and development is not seen as important in psychoanaly-sis, but symptoms are considered to have an unconscious psycho-logical basis. Descriptive phenomenology makes no comment upon the unconscious mind. It depends upon the subject being able to describe internal experiences, i.e. conscious material. Descriptive psychopathology is not dependent upon brain localiza-tion but on clarifying the nature of the subjective phenomena in discussion with the patient; if links can then be shown between certain phenomena and speciﬁ  c brain lesions, that is, of course, 
highly advantageous in furthering psychiatric knowledge. Descriptive phenomenology can be a unifying factor between concepts of brain and mind; it does not depend on philosophical stance on the nature of mind or brain.
Disorders of perception

Perception is not restricted to the screening of physical signals by sense organs but implies the processing of these data to represent reality. Ideas from the philosophy of mind have inﬂ  uenced psychi-
atric concepts of perception and the constitution of reality. Recently the distinction between sensory screening and interpretation has been conﬁ  rmed by neurocognitive research.
Hundert
(3) used the philosophical idea contained in the Kantian 
distinction between a priori  categories and a posteriori  experiences 
as a framework for differentiating perception by the sense organs from the secondary evaluation process. Kant’s emphasis on the interplay between ‘distal’ perception and ‘proximal’ conceptualiza-tion can be exempliﬁ  ed by the perception and recognition of faces,

disturbed in the Capgras syndrome and to a lesser degree in schizo-phrenia. The processing of visual perception is organized on at least four levels of complexity: the retina, the lateral geniculate body, the occipital visual cortex, and the hippocampus. The occipi-tal cortex, where we actually ‘see’ , does not contain an image any more than do the preceding levels; rather, it holds a database composed of signals from speciﬁ  c neurones for edges, angles, 
curves, sudden movements, and so on. Compared with the percep-tual screen of the retina, these signals are ‘scrambled’ but even so 
they form a notion of what we perceive as reality. Recognition of 
faces needs further processing, probably in the hippocampal area where associations from other cortical ﬁ  elds are integrated with the

49
visual information (e.g. the voice belonging to the face). In psychi-
atry we deal with heterogeneous aetiologies, and perceptual distur-bances may originate from different levels of processing, usually from a more integrated level than in neurological disease, and fur-ther from the immediate screening of physical stimuli by the sense organs. Thus, psychiatric disorders of perception affect different stages of information processing—from disturbances in the sense organs to complex phenomena involving feelings and ideas.
Here we shall mainly focus on hallucinations and some related 
phenomena, which are relevant for psychiatric illnesses.
Deﬁ nitions of perceptual disturbances
Cutting(4) deﬁ nes hallucination  as ‘perception without an object 
or as the appearance of an individual thing in the world without any corresponding material event’ . The problem with this deﬁ  ni-

tion is that although some hallucinating patients mistake a halluci-natory perception for a real one, others can differentiate them: as demonstrated experimentally by Zucker,
(5) there is an ‘as if’ quality 
even when patients assert that they perceive real objects or events. Voices described in detail by hallucinating patients were imitated and presented to the patients without warning. They had no difﬁ  -
culty in discriminating these external voices from their hallucinations. For this reason Janzarik
(6) deﬁ ned hallucinations, without associat-

ing them with perception at all, as ‘free running psychic contents’ (using a concept similar to Jackson’s disinhibition). In keeping with this idea, lack of perception may facilitate hallucinations as in sen-sory deprivation or in the oneiroid states of paraplegic patients.
(7)
The perceptual quality of hallucinations differs from similarity 
to sensory experiences, as in delirium, to the bizarre apprehensions of some with schizophrenia. Also, the extent to which the person is affected varies from descriptions of hallucinations as ﬁ  lm-like in 
amphetamine psychoses to the affectively overwhelming experi-ences of hallucinations associated with delusional mood.
The term pseudohallucination , sometimes, is used to describe a 
perception recognized as unreal . Jaspers
(8) deﬁ ned hallucination as

(8) deﬁ ned hallucination as 
corporeal and tangible; pseudohallucination lacks this quality. According to Jaspers, pseudohallucinations are not tangible and real as hallucinatory perceptions; they appear spontaneously; they are discernible from real perception; and, they are difﬁ  cult, but not 
impossible, to overcome voluntarily. Kandinsky illustrated Jaspers’ deﬁ nition of pseudohallucination: spontaneously arising images 
of acquaintances arose when a patient kept his eyes closed. He was fully aware of the unrealistic character of this experience and could abandon it by opening his eyes. Thus, to Jaspers, pseudohal-lucinations are close to imagined images except that they arise spontaneously and are more vivid. Jaspers’ deﬁ  nition is not used 
consistently; in some Anglo–American literature it has been sufﬁ cient for the deﬁ  nition of pseudohallucination that there be

consistently; in some Anglo–American literature it has been sufﬁ cient for the deﬁ  nition of pseudohallucination that there be 
subjective awareness that the percept lacks a real external equivalent 
and arises from the subject.
Imagery  describes vivid visual experiences, which can be produced 
and manipulated voluntarily. It occurs in trance states when the perceptions are produced voluntarily, but are more real and last longer than in a normal state.
Illusions  differ from hallucinations in being based on a misin-
terpretation of a real object or event, often associated with a mood. Illusions have to be distinguished from delusional perceptions which are percepts based on real objects to which an incorrect meaning has been attached. In delusional perceptions this ‘error’ cannot be corrected by the patient; in illusions the patient can 
recognize the true meaning.
Kurt Schneider described Gedankenlautwerden  (écho de la pensée ,

or thoughts heard aloud) as a transitional phenomenon between vivid imagination and auditory hallucination. The patient recog-nizes that the words he hears are his own thoughts, but he cannot voluntarily control them. Gedankenlautwerden  can disturb concen-
tration when talking to other people. It can be differentiated from 
thought insertion and from auditory hallucinations in that there is a lesser degree of alienation.
Klosterkötter
(9) has described transitions from elementary

(9) has described transitions from elementary 
unformed hallucinatory sensations, like a crack, bump, or hiss, through more meaningful perceptions which still can be localized ‘inside’ the head, to complex hallucinations which become part of a delusional cognitive structure. These transitions were related to increasingly affective involvement in the themes of the hallucina-tion. Klosterkötter’s observations support Janzarik’s interpretation of hallucinations as ‘free running psychic contents’ , as do experi-mental studies of model psychoses which show a regular sequence of three psychopathological states: vegetative arousal, affective change, and ‘productive’ phenomena-like hallucinations and delusions.
Some misperceptions, found mainly in schizophrenic patients,

Some misperceptions, found mainly in schizophrenic patients, 
are less complex than hallucinations, appear to be more closely related to neuropsychological disturbances, and include less systematization. They include optical distortions  of size, colour, 
distance, and perspective, which can resemble experiences reported by people taking cannabis or other psychoactive drugs. These ﬂ  uc-
tuating, circumscribed misperceptions exemplify the way in which a more complex phenomenon of psychopathology can be built upon something more basic. Krause et al .
(10) videotaped the

(10) videotaped the 
non-verbal behaviour of schizophrenic patients and their healthy partners in a conversation. Brief non-verbal cues play an important part in dialogue. Schizophrenic patients miss these non-verbal brief cues and are poor at judging the intentions of others; their own non-verbal communication is poorly co-ordinated. The ensu-ing dysfunction diminishes social competence. Schizophrenic painters, trained before the onset of their illness, have been shown to misperceive perspective.
(11)
Sensory modalities
Hallucinations can affect every sense modality. The most common, in the idiopathic psychoses, are auditory hallucinations , usually

(11)
Hallucinations can affect every sense modality. The most common, in the idiopathic psychoses, are auditory hallucinations , usually 
in the form of voices, although other kinds of sound may be asso-ciated with delusional contents. Voices talking to each other about the patient, and voices commenting about the patient’s ongoing acting or thinking, are considered to be typical of, but not speciﬁ  c 
to, schizophrenia.
(12) Voices calling the patient’s name or talking 
without comments to the patient are diagnostically non-speciﬁ  c.
Visual hallucinations  are most frequently found in organic 
psychosis, particularly delirium, in which they may occur for only a couple of hours during the night if the syndrome is not full blown. Visual hallucinations, more often than those in other sensory modalities, depict animals and scenes with several persons. In alcoholic delirium in particular, optical hallucinations of ﬁ  ne

structures (such as hairs, threads, or spider webs) occur, and are especially likely to appear if the patient stares at a white wall. A typical, although not speciﬁ  c, combination of hallucination and 
delusion in organic psychosis is the ‘siege experience’ , in which 1.7 descriptive phenomenology

SECTION 1  the subject matter of and approach to psychiatry 50
patients believe they are besieged by enemies and have to bar their 
doors and windows.
Bodily, tactile, or coenaesthetic hallucinations  are associated 
more often with schizophrenia than with affective or organic psy-choses. The phenomenology includes simple tactile sensations of the skin, sexual sensations, sensations of the contraction, expan-sion, or rotation of inner organs, or atypical pain. Usually these sensations are associated with delusional explanations. Tactile hallucinations localized in the skin can underlie the delusion of 
parasitosis . Elderly patients in the early stages of organic cerebral 
alterations are at highest risk.
Coenaesthesia  is a bodily misperception, which may last for 
minutes to days. It ﬂ  uctuates (sometimes in relation to stress), and is 
usually not attributed to external agents or explained by delusional ideas. Patients seldom report them spontaneously. Klosterkötter
(9)

(9)
suggests that when coenaesthesia is attributed strongly to external inﬂ uences, it is likely to be followed by schizophrenia.
Hallucinations may be gustatory  or olfactory , for example, a 
smell of gas (perhaps thought to emanate from neighbours trying to kill the patient). Blunting of gustatory sensations or mispercep-tion of food as oversalted or overspiced is occasionally reported by melancholic patients.
Aetiological theories of hallucination
Aetiological theories are of three kinds:
1 overstimulation affecting different levels of information 
processing;
2 failure of inhibition of mental functions;
3 distortion of the processing of sensory information at the inter-
pretive level.
The work of Penﬁ  eld and Perot(13) has suggested that overstimu-
lation  may be a pathogenic mechanism. They stimulated the tem-

poral regions of 500 patients, of whom 8 per cent reported scenic hallucinations, some in several modalities. Stimulation of the visual occipital cortex led to simple hallucinations-like ﬂ  ashes, 
circles, stars, or lines. This phenomenon has been observed in drug-induced experimental psychosis. It is interesting that schizophrenic patients can usually distinguish drug-induced hallucinations from those arising from their disorder. Using neural network theories, Emrich
(14) simulated hallucinations by using Hopﬁ  eld networks; 
overloading the storage capacity of the network generated what appeared to be the equivalent of hallucinations.
Disinhibition  theory originated with Hughlings Jackson, who

Disinhibition  theory originated with Hughlings Jackson, who 
considered that productive symptoms were caused by the disinhi-bition of controlling neural activities, while negative symptoms resulted from damage to the systems, which generate the produc-tive symptoms. More recently, sensory deprivation research has yielded inconsistent results; hallucinations, narrowly defined, seldom occur after deprivation, which may be of greater relevance to vivid, usually visual, imaginative experiences. Disinhibition may also underlie the ‘hypnagogic hallucinations’ which can occur in healthy subjects shortly before they fall asleep.
The role in the production of hallucinations of post-sensory 
interpretation and evaluation of stimuli is uncertain. In these 
terms, hallucinations are a sort of deception, but this is not a sufﬁ  -

cient description of their nature. Recent neurophysiological hypotheses and ﬁ  ndings from neuroimaging studies have suggested that there is an ‘inner censorship’ involved in clarifying ambiguities 
of perception.
(14)
Disorders of thinking
Types of thinking
Three types of thinking can be distinguished which represent a continuum, without sharp boundaries, and intertwined in everyday life, from low to high regard for external reality and goal-directness: fantasy thinking, imaginative thinking, and rational thinking.
(15) Since each of these types can predominate under 
some conditions, this distinction is useful to understand certain abnormal phenomena.
Fantasy thinking  (also called dereistic or autistic thinking) pro-

duces ideas, which have no external reality. This process can be completely non-goal-directed, even if the subject is to some extent aware of the mood, affect, or drive, which motivates it. In other cases fantasy serves to exclude reality, which may require material with which the subject does not want to engage. This type of fan-tasy thinking is directed. Its goal is not to solve a problem but to avoid it via neglect, denial, or distortion of reality. Normal subjects use fantasy thinking deliberately and sporadically. However, if its content becomes subjectively accepted as fact, it becomes abnor-mal. This pathological exclusion of reality can remain limited in 
extent (e.g. in hysterical conversion and dissociation, pseudologia phantastica, and some delusions) or it may be manifested as with-
drawal from the real world.

Rational (conceptual) thinking  attempts to resolve a problem 
through the use of logic, excluding fantasy. The accuracy of this endeavour depends on the person’s intelligence, which can be affected by various disturbances of the different components involved in understanding and reasoning.
Imaginative thinking  comes between fantasy thinking and

Imaginative thinking  comes between fantasy thinking and 
rational thinking. It is a process of forming a representation of an object or a situation using fantasy but without going beyond the rational and possible. This thinking is goal-directed but frequently leads to more general plans than the solution of immediate problems. Imaginative thinking becomes pathological if the person attaches more weight to his representation of events than to other objectively equally possible interpretations. In overvalued ideas, the imagined interpretation surpasses other interpretations in strength; in delusions, all other possibilities are excluded.
Delusions
The term ‘delusion’ signiﬁ  es a complex ediﬁ  ce of thinking in 
which ‘delusional ideas’ are linked with other (‘normal’) thoughts. Delusions are communicated to others in the form of judgement. 
In this context, the term ‘delusional idea’ customarily refers to

In this context, the term ‘delusional idea’ customarily refers to 
pathologically false judgement for which three criteria have been proposed: the unrivalled conviction with which they are held, their lack of amenability to experien ces or compelling c ounter-a rgum ents, 
and the impossibility of their content.
(16) The last criterion must be 
discarded for two reasons. Firstly, collective beliefs derived from the socio-cultural setting of a person can be considered, in other surroundings, as false or impossible. Taking this into account, delusion is often deﬁ  ned as a ‘false unshakable belief, which is out 
of keeping with the patient’s social and cultural background’ .
(15)
Secondly, in certain delusions (e.g. delusional jealousy) the content

51
does not go beyond the possible. Thus delusions are best deﬁ  ned as 
overriding, rigid, convictions which create a self-evident, private, and isolating reality requiring no proof.
(17)
(a) The genesis of delusions
Jaspers(18) introduced a distinction between primary and second-
ary delusions. He supposed that the ﬁ  rst, called true delusional 
ideas , are characterized by their ‘psychological irreducibility’ , 
whereas the second, called delusion-like ideas , emerge understand-
ably from disturbing life experiences or from other morbid phe-nomena, such as pathological mood state or misperception. This led to the assumption that primary delusions are the direct expres-sion of the underlying condition considered to be the basis of schizophrenia. Four types of primary delusion have been distin-guished in this perspective.
1Delusional intuition  (autochthonous delusion), occurring 
spontaneously, ‘out of the blue’ .
2Delusional percept , in which a normal perception acquires

2Delusional percept , in which a normal perception acquires 
a delusional signiﬁ  cance. Schneider
(19) assumed that ‘psycho -
logical irreducibility’ was clearly evident in this process, and included delusional percept  among his ‘ﬁ  rst-rank symptoms’ of 
schizophrenia.
3Delusional memory  can be distorted or false memory coming 
spontaneously into the mind, like delusional intuition. In other cases they occur, like delusional percept, in two stages, which means that normal memories are interpreted with delusional meaning.
4Delusional atmosphere  refers to an ensemble of minuscule

4Delusional atmosphere  refers to an ensemble of minuscule 
and almost unnoticed experiences, which impart a new and bewildering aspect to a situation. The world seems to have been subtly altered; something uncanny seems to be going on in which the subject feels personally involved, but without knowing how. From this uncertainty evolves ﬁ  rst certainty of self-reference, and 
then the formation of fully structured and speciﬁ  c delusional 
meaning. The apparent change in the surrounding situation is accompanied by tension, depression, or suspicion, and by anxious or even exciting expectations, so that it is often called ‘delusional mood’ .
The primary–secondary distinction assumes that the delusional

The primary–secondary distinction assumes that the delusional 
atmosphere is part of the process underlying all primary delusional phenomena. If this preliminary disturbance is not perceived clearly or is not communicated by the patient as a general change in the situation, delusion may be manifested only as delusional percept, intuition, or memory. When the initial change in atmosphere is experienced clearly, a subsequent alteration in the environment, or 
a fully formed delusional idea, can lead to release from the preced-
ing perplexity. The origin of primary delusions is commonly attributed to a basic cognitive anomaly disturbing information-processing, which reduces the inﬂ  uence of past experience on current 
perception. This is considered to entail a heightened awareness of irrelevant stimuli and an ambiguous unstructured sensory input allowing the intrusion of unexpected and unintended material from long-term memory.
(20)
(b) The content of delusions

(20)
The content of delusions is determined by the mood in which they emerge and evolve, by the patient’s personality and socio-cultural background, and by previous life experiences. In principle, the con-
tent can embrace all kinds of presumptions in separate categories. The following six delusional themes are usually distinguished:
◆delusion of persecution  based on the assumption that the 
patient is pursued, spied upon, or harassed
◆delusional jealousy
◆delusion of love  characterized by the patient’s conviction that 
another person is in love with him or her
◆delusion of guilt , unworthiness, and poverty which may some-
times reach the degree of ‘nihilistic delusion’ , in which the patient believes the real world has disappeared completely
◆grandiose delusion  in which patients are convinced that they 
have great talents, are prominent in society, or possess supernat-ural powers
◆hypochondriacal delusion  founded on the conviction of having

◆hypochondriacal delusion  founded on the conviction of having 
a serious disease.
The mood state when delusional ideas emerge favours certain 
themes. Delusion of guilt, or unworthiness, and hypochondriacal delusion are strongly linked with depression. Grandiose and erotic delusion generally occurs in excited or manic states. Delusions of persecution and jealousy emerge most frequently from suspicious mood states or a delusional atmosphere, but may occur in depressed subjects.
Some further speciﬁ  c contents of delusions are:
◆religious delusion , which may occur with grandiose delusion or 
delusion of guilt
◆delusion of infestation , a subtype of hypochondriacal delusion, 
and characterized by the conviction of infestation by small organisms
◆delusional misidentiﬁ  cation  in which the patient believes, on

◆delusional misidentiﬁ  cation  in which the patient believes, on 
the basis of a delusional percept, that a perceived person has been replaced by an imposter, or in which he is convinced that another person has been physically transformed into his own self
◆delusion of control  in which the patient experiences sensations, 
feelings, drives, volition, or thoughts as made  or inﬂ  uenced by 
others (this schizophrenic delusion is believed to result from cognitive dysfunction consisting of a failure of the system which monitors willed intentions).
(21)
(c) The structure of delusions
1 The alternatives, ‘logical’ or ‘paralogical’ , indicate whether or not 
the connection of ideas is consistent with logical thinking.
2 The notions, ‘organized’ or ‘unorganized’ , indicate whether or not 
the delusional idea is integrated into a formed concept. Highly organized, logical delusions are described as systematized .

3 The relationship between delusion and reality varies:
◆ in polarized delusion , delusional reality is inextricably inter-
mingled with actual fact
◆ if the delusional belief and reality exist side by side without 
inﬂ uencing each other, we speak of juxtaposition
◆ in autistic delusion  the patient takes no account of reality 
and lives in a delusional world.1.7 descriptive phenomenology

SECTION 1  the subject matter of and approach to psychiatry 52
Overvalued idea
An overvalued idea is an acceptable, comprehensible idea pursued 
beyond the bounds of reason.(22) Overvalued idea causes disturbed 
functioning or suffering to the person himself or others.
Overvalued ideas of prejudice (overvalued paranoid ideas) 
are characterized by an underlying self-referent interpretation of the behaviour or sayings of others; patients assume themselves to be overlooked, slighted, unfairly treated, provoked, or loved. Overvalued apprehension may become apparent as morbid jeal-ousy, hypochondriacal phobia (e.g. parasitophobia), or dysmor-phophobia, in which patients assume that they attract attention because of a real or presumed bodily defect. In anorexia nervosa subjects are preoccupied by the endeavour to remain thin, and in 
transsexualism by the desire to change gender because they feel that they belong to the opposite sex.

Overvalued ideas generally occur with abnormal personality 
under stressful situations. Those with paranoid personality traits may develop, on the basis of a presumed injustice, querulous, or litiginous overvalued idea. Sometimes ideas become overvalued only during abnormal mood states (of various origins) which set aside counterbalancing inﬂ  uences.
Thinking in mood disorders
The content of thought in mood disorders is coloured by affect. 
Negative thinking about self, the future, and the world prevails.(23)
Mishaps and failures are attributed to personal faults; success is attributed to the action of other people. This depressive thinking spreads from the starting point of negative life events to more gen-eral events, and it tends to become long lasting. The ﬁ  xed view-

point that emerges is called ‘cognitive schema’ . After recovery from an acute episode this schema may become latent, but it can be reactivated by distressing life events. It can also prolong symp-toms. Negative thinking started by minor misfortunes can become autonomous, driving down mood—which in turn intensiﬁ  es neg-
ative thinking. The negative schema can prolong a depressive epi-sode or precipitate a new one. It is probable that such schemas are activated by both cognitions and emotions. Guilty thoughts are closely connected with this type of thinking, and may reach the 
intensity of a delusion. T o a degree, guilty thinking in depression is dependent on culture. In mania, the content of thought is related

intensity of a delusion. T o a degree, guilty thinking in depression is dependent on culture. In mania, the content of thought is related 
to the mood of elation, with diminished self-criticism and exces-sive self-importance. In phobic and other anxiety states, thinking centres on situations leading to anxiety. Typical contents of delu-sional thinking in depression concern guilt, religious failure, condemnation, personal insufﬁ  ciency, impoverishment, hypo-
chondriasis, and nihilistic ideas. In mania, delusional ideas may be feelings of spiritual or economic power. In contrast with schizo-phrenic delusions, affective delusions grow out of the underlying, excessive mood and do not appear as something new and alien to the personality.
Phobic and anankastic phenomena
Phobic and anankastic (obsessional) phenomena have in common that the patient experiences them as unwanted, but cannot sup-press them. They often occur together.
(a) Phobia

(a) Phobia
Phobias are inappropriate, exaggerated fears which are not under voluntary control, cannot be reasoned away, and entail avoidance behaviour.
(24) The fears are kindled by particular stimuli. These 
may either be perceived objects, such as animals (animal phobia) or pustules (in some illness phobias), or situa tions such as open places (agoraphobia) or conﬁ  ned rooms (claustrophobia).
Phobias initially triggered by a very speciﬁ  c stimulus can eventu-

ally generalize. Thus, an elevator phobia may become extended to all kinds of closed rooms. Some phobias are linked with broader circumstances from the beginning. In social phobia, for instance, patients avoid meeting people because they fear that they will be noticed. Identical types of fears can be triggered by different stimuli in different subjects. Thus, illness phobia is activated in some patients by observed body changes, but in others by situations involving the risk of infection.
Phobias are characterized by avoidance behaviour: patients 
avoid anxiety-provoking objects or situations. Because of stimulus generalization, this can lead to severe impairment; for instance, they cannot leave home.
(b) Anankastic symptoms
Anankastic phenomena occur as obsessions or compulsions:
1 Obsessions occur as repeated thoughts, memories, images,

1 Obsessions occur as repeated thoughts, memories, images, 
ruminations, or impulses that patients know to be their own but are unable to prevent. The content of these ideas is often unpleasant, terrifying, obscure, or aggressive.
2 Compulsions are actions, rituals, or behaviours that the patient 
recognizes as part of his own behaviour, but cannot resist.
(c) Combined syndromes
In phobic–anankastic syndromes patients attempt to reduce their phobic fears by certain actions, such as hand washing in the case of an infection phobia. If obsessional thoughts or impulses induce anxiety (e.g. obscene ideas during worship, or the impulse to lean too far over a balustrade) and entail the avoidance of the situations that provoke them, the term anankastic–phobic syn-drome is used.
Phobias, obsessions, and compulsions result most frequently 
from neurotic conﬂ  icts, but they also occur with functional or

from neurotic conﬂ  icts, but they also occur with functional or 
organic mental disorders. Anankastic personalities, characterized by perfectionism, rigidity, sensitivity, and indecisiveness, are especially prone to develop obsessions and compulsions.
Disorder of the thinking process
Disturbance of thinking may be recognized by the patient himself or deduced by an observer from the subject’s speech.
Impairments of thought production are conventionally named 
‘formal thought disorder’ and contrast with abnormalities of the ‘content of thought’ observed in delusions. In the deviant reality-testing of deluded patients there is always a disturbance of the form of thinking.
(a) Disorders of the ﬂ  ow of thinking
Each remembered idea is linked with a number of other notions, 
related closely as well as distantly. In rational thinking, a ‘determin-ing tendency’
(25) guides the ﬂ  ow of ideas in the chosen direction

(25) guides the ﬂ  ow of ideas in the chosen direction 
and excludes associations which do not conform with this goal. This procedure can be disturbed in various ways which are commonly grouped together under the heading of ‘formal thought disorder’ .

53
(i) Disturbances of the speed of thinking
In acceleration  of thinking, associations are still formed normally 
but at grossly accelerated speed. The goal is not maintained for long and the intervention of new thoughts produces ‘ﬂ  ight of ideas’ .
Retardation  refers to a slowing down of the thinking process, 
which hampers formation of associations and may prevent reach-ing the original goal of thoughts. This results in difﬁ  culties in con-
centration and decision-making.
Acceleration and retardation of thinking are due to a change of 
affect, and are characteristic of mood disorders.
(ii) Circumstantiality
In circumstantiality the determining tendency is maintained but the

In circumstantiality the determining tendency is maintained but the 
patient can reach the goal only after having exhaustively explored unnecessary associations arising in his mind. When answering a question, he relates many irrelevant details before returning to the point. This inability to exclude unimportant associations occurs in organic mental disorders and in mental retardation.
(iii) Perseveration
Perseveration is found in organic mental disorders and is deﬁ  ned 
as an inability to shift from one theme to another; a thought is retained long after it has become inappropriate in the given con-text. For example, a patient may give a correct answer to the ﬁ  rst 
question, but repeats the same response to a subsequent, completely different inquiry.
(iv) Interruptions in the ﬂ  ow of thinking
Thought blocking  is a sudden unintended cessation in the train of

Thought blocking  is a sudden unintended cessation in the train of 
thought, experienced by the patient as ‘snapping off’ . After this break, which may occur in the middle of a sentence, the previous thought may be taken up again or replaced by another. Thought blocking occurs in organic states, in depression, and frequently in schizophrenia where it is described as part of negative thought disorder.
In loosening of association  the ﬂ  ow of thinking is interrupted 
by deviation towards distant or unrelated thought, in contrast with ﬂ ight of ideas in which there is only a speeding up of access to 
nearby associations. Loosening of association is a type of formal thought disorder. In tangentiality  the ideas deviate towards an 
obliquely related theme. In fusion , different kinds of association

obliquely related theme. In fusion , different kinds of association 
evoked by an original thought are blended to produce a word or 
sentence. Derailment  is characterized by the interpolation of ideas 
which neither the patient nor the observer can link with the previ-ous stream of thought. Muddling  designates an extreme degree 
of derailment and fusion.
In organic states, incoherent thinking, which is clinically similar 
to derailment, may be attributable to a primary intellectual impair-ment and not to an increased spread of associations.
(b) Overinclusive thinking
This kind of thought disorder is not based on an interruption of the ﬂ  ow of thought but on an inability to preserve conceptual 
boundaries; ideas only distantly related to the concept under con-sideration become incorporated within it,
(26) for example, when 
asked to indicate the essential components of a room ,table  might 
be included as well as ceiling ,wall, and ﬂ oor.
(c) Concrete and abstract thinking

In organic mental disorders and mental retardation, inability to 
think abstractly may be attributed to a diminished capacity to structure a concept. There have been various theories used 
to explain the concrete thinking  of schizophrenia, involving 
memory, conceptualization, and intrusion of delusions. The pro-cess may be enhanced by loosening of associations. The fact that schizophrenia sometimes manifests excessively abstract think-
ing may also be explained by a disturbance of working memory 
such that the concrete meaning of the initial thought is not retained.
(d) Disorder of control of thinking
In obsessions  and compulsions  the subject recognizes his 
thoughts as being produced by himself but is unable to control them.
In passivity of thought , the patient experiences his thoughts

In passivity of thought , the patient experiences his thoughts 
as manipulated by outside influences. The interpretation resulting from this feeling is described as ‘thought withdrawal’ , ‘thought insertion’ , or ‘thought broadcasting’ (which denotes the patient’s conviction that his thoughts are diffused to other people). These ‘delusions of the control of thought’ were included by Schneider
(27) among his ‘ﬁ  rst-rank symptoms’ of 
A particular variation of thought insertion occurring in 
schizophrenia is crowding of thoughts . In this condition, the 
patient experiences an excessive increase in the amount of thoughts imposed from the outside and compressed in his mind.
Language and speech disorder
‘Speech disorder’ refers to defects in the ability to generate

‘Speech disorder’ refers to defects in the ability to generate 
and articulate verbal statements, whereas ‘language disorder’ designates deﬁ  cits in the use of language. The terms ‘aphasia’ 
and ‘dysphasia’ are often used interchangeably for speech disorders.
(a) Disturbed generation and articulation of words
Aphonia  designates the inability to vocalize. Thus, whispering 
occurs in somatic illnesses (paralysis of cranial nerve IX or disease of the vocal cords) and hysteria. Dysphonia  is a somatic impairment 
with hoarseness.
Dysarthria  refers to disorders of articulation occurring in various 
malformations or diseases, which impair the mechanisms of phonation, in lesions of the brain stem, in schizophrenia, and in psychogenic disorders.
The causes of stuttering and stammering  are unclear, but are 
sometimes considered to be of neurotic origin. Logoclonia  (the 
spastic repetition of syllables) occurs in Parkinsonism.
(b) Disturbance in talking

‘Disturbances in talking’ was proposed by Scharfetter(28) as a 
generic term for disorders of speech or language not belonging to the preceding group of disturbances.
Changes in volume of sound and in intonation  occur in 
affective and schizophrenic states, and refer to loud excited and quiet monotonous speech.
Bradyphasia  (decelerated talking) and tachyphasia  (accelerated 
talking) occur in mood disorders, schizophrenia, and organic dysphasias.
Logorrhea  (verbosity) is observed in various disorders, especially 
in manic states.
Alogia  (poverty of speech) is a decrease in spontaneous talking; 
it occurs in depression and schizophrenia.1.7 descriptive phenomenology

SECTION 1  the subject matter of and approach to psychiatry 54
In poverty of content of speech , the amount of speech is 
adequate but conveys little information. This is often related to schizophrenic disorganization of thinking.
V erbigeration  is the monotonous repetition of syllables and 
words observed in organic language disorders, schizophrenia, and agitated depression.
Echolalia  is the repetition of words or parts of sentences that are 
spoken by others. It can be observed in schizophrenia, organic states, and subnormality.
Sometimes patients give approximate answers : i.e. they avoid 
giving the correct answer to a question that they have understood, just missing being correct. This occurs in organic disorders, schizo-phrenia, and hysteria.
Paraphasia  denotes the enunciation of an inappropriate sound 
instead of a word or phrase. This happens in organic speech disorders but may also have psychogenic causes.
Speech may be unintelligible for various reasons. Para-

grammatism  and parasyntax  (loss of grammatical and syntactical 
coherence) occur in organic mental disorders and excited manic states, and in schizophrenia, when severe thought derailments become manifest as ‘word salad’ . Private symbolism  can be 
observed in schizophrenia in three forms: use of existing words with a particular symbolic meaning, creation of ‘neologisms’ (new words with an idiosyncratic meaning), and production of a private incomprehensible language, which may be spoken (cryptolalia) or written (cryptographia).
Mutism  (refraining from speech) may be found in various kinds 
of psychiatric disorder. It is a cardinal feature of stupor and also occurs as an ‘hysterical’ reaction to stress.
Pseudologia fantastica  is characterized by ﬂ  uent lying, which is

Pseudologia fantastica  is characterized by ﬂ  uent lying, which is 
developed into a fantastic construct. This ‘mythomania’ occurs in histrionic and asocial personality disorders.
(c) Organic language disorders
This refers to impairments of spontaneous language, naming, writing, and reading, occurring as a result of brain dysfunction. These disorders can be divided into ‘sensory’ (receptive), ‘motor’ (expressive) defects, or both combined, containing the following principal subcategories:
(i) Sensory language disorders
In primary sensory dysphasia  the patient cannot understand the 
speech of others. His own speech remains ﬂ  uent, but contains

speech of others. His own speech remains ﬂ  uent, but contains 
errors in the use of words, syntax, and grammar. Writing and reading are also impaired. If, in this condition, the patient’s speech becomes unintelligible, the disturbance is called ‘jargon aphasia’ . If only the repetition of a message is disturbed, the disorder is named ‘conduction dysphasia’ .
In pure word-deafness  speech, reading, and writing are ﬂ  uent 
and correct. The patient hears words as sounds, but cannot recog-nize their meaning. In pure word-blindness  (alexia) speech 
and writing are normal but the patient cannot read with under-standing.
(ii) Motor language disorders
In primary motor dysphasia  the verbal or written expression of 
words and the construction of sentences is disturbed, but the understanding of speech and writing are preserved.
In pure word-dumbness  the disturbance is limited to an inabil-

ity to produce and repeat words at will. Pure agraphia  is an isolated inability to write. Nominal dysphasia  is an inability to produce 
names and nouns.
Disorders of intellectual performance
(a) Conceptualization of intelligence
‘Intelligence’ refers to the capacity to solve problems, to cope with new situations, to acquire skills through learning and experience, to establish logical deductions, and to form abstract concepts. There has been a classical debate amongst psychologists as to whether intelligence represents different and speciﬁ  c abilities or a 
unitary, general factor of intelligence.
(b) Measurements of intelligence
Individual intellectual capacity is graded by reference to the intel-ligence quotient ( IQ), which is deﬁ  ned as the ratio of a subject’s

Individual intellectual capacity is graded by reference to the intel-ligence quotient ( IQ), which is deﬁ  ned as the ratio of a subject’s 
intelligence to the average intelligence for his or her age. The assess-ment of intelligence is considered in Chapter 1.8.3.
In addition to the global assessment of intelligence, numerous 
tests have been developed to assess organic impairment, scholastic achievement, and aptitude.
(c) Mental retardation (learning disability)
If the development of intellectual performance does not reach an IQ level of 70, the condition is designated ‘mental retardation’ . This is subdivided according to severity, with four levels recognized in ICD-10:
◆ mild (IQ 50–69)
◆ moderate (IQ 35–49)
◆ severe (IQ 20–34)
◆ profound (IQ below 20).
The causes of mental retardation are considered in Section 10.
Disorders of later onset
In these disorders normally developed intellectual performance

In these disorders normally developed intellectual performance 
declines. This can occur as a result of organic brain disorders, and in psychotic and affective disorders.
Organic disorders may have toxic, traumatic, inﬂ  ammatory, or 
hypoxic causes. If these conditions are treated successfully, the dis-turbance can be arrested or even reversed.
In dementia there is a progressive disintegration of intellectual 
function, which usually begins insidiously and is often ﬁ  rst recog-
nized through an impairment of memory.
In psychotic states the distorted testing and evaluation of reality 
can impair intellectual performance. In schizophrenia, formal thought disorder may contribute to this effect.
Severe affective disorder can impair perception, attention, 
and motivation, leading to poor intellectual performance. These

and motivation, leading to poor intellectual performance. These 
disturbances are observed more often in depression, but can occur 
in manic mood.
Disorders of mood
This section outlines the psychopathological elements comprising mood disorders, in particular the different varieties of depression, mania, anxiety state, and depersonalization.
Mood  is a state of mind, which is longer lasting than affect or 
feeling. Mood encompasses all mental processes; it is not inﬂ  uenced

55
by will, and is strongly related to values. Heidegger(29) has consid-
ered mood as the fundamental expression of an individual’s being. Kierkegaard
(30) emphasized the role of existential orientation in 
determining mood, especially general anxiety.
The extent and type of deviation of mood is important in 
affective disorders. Although there are no sharp boundaries between the normal variations and pathological states of mood, severe states are clearly abnormal and difﬁ  cult to understand. Mood 
can be abnormal in several ways: sad or anxious in depressive dis-orders; euphoric in mania; irritated in mania or agitated depres-sion; dysphoric in depression or in mixed manic—depressive disorders; morose in chronic-depressed states, often with a compo-nent of resentment; blunted (the feeling of ‘having no feelings’ or ‘petriﬁ  ed’ feelings) in prolonged, severe depressive disorder. 
Stanghellini
(31) analysed depressed patients and described how

(31) analysed depressed patients and described how 
morose affect may emerge when the patient struggles against declining abilities and experiences resistance. In such cases feelings of timidity and despair may contrast with an outward appearance of hostility.
Two types of euphoria  should be differentiated: one shows 
elation and feelings of increased spiritual, intellectual, or physical power, and the other results from disinhibition in organic states and dementia. This second type, rather than elation, may show lack of interest and an attitude of negligence towards the patient’s actual situation.
These abnormal moods are related to altered bodily feelings  and 
thinking.
Abnormal somatic  symptoms can be divided into physical symp-
toms, such as cardiovascular dysregulation, increased sweating, and 
feeling cold, and hypochondriacal symptoms, such as headache

feeling cold, and hypochondriacal symptoms, such as headache 
and feeling of tightness in the chest, heavy limbs, being choked, or difﬁ culty in swallowing. These latter symptoms are related to feel-
ing of loss of energy.
Lopez-Ibor
(32) suggested the term ‘depression-equivalent’ for 
conditions in which somatic symptoms (e.g. headaches which vary on a diurnal pattern) dominate the clinical picture. Cross-cultural research has found higher rates of such somatic symptoms in depression in Africa
(33) and South America,(34) and a lower rate of 
guilt compared with Western industrialized countries. However, the results are not wholly consistent and variation may reﬂ  ect cul-
tural differences or differing patterns of consultation with doctors, and what patients expect doctors to treat.
A feedback loop may develop between anxiety and physical

A feedback loop may develop between anxiety and physical 
arousal , e.g. palpitations, which accompanies it.
(35,36) The pre-
valence of mitral valve prolapse is higher in anxiety disorder (37 per cent) than in the general population (5 per cent).
(37) This 
ﬁ nding is consistent with the idea that palpitation may lead to a 
conditioned anxiety response. The behaviour therapy technique of exposure aims to decondition this reﬂ  ex. In social phobia and 
panic disorder anxiety is often complicated by anxiety-provoking situations which may lead to severe social disablement. Somatic symptoms of anxiety may be so prominent in some depressive states that patients are misdiagnosed as medically ill, with loss of weight, atypical pain, or sensory or motor disturbances. This type of depression has been called ‘depressio sine depressione’ , or ‘somatoform depression’ .

Disturbances of diurnal rhythm  can inﬂ  uence all the other 
symptoms of mood disorder.
(38) There are changes associated with sleep in the electroencephalogram, with shorter REM latency 
(phase advance), and also changes in endocrine and cardiovascular circadian rhythms. In depression, sleep disturbance is characterized by early awakening, whereas falling asleep in the evening is often undisturbed. About 70 per cent of melancholic patients show diurnal distribution of mood, psychomotor activity, somatic symptoms, and slowed and impoverished thinking.
Psychomotor retardation or acceleration  is one of the most

Psychomotor retardation or acceleration  is one of the most 
prominent symptoms of mood disorder. Often the patient’s appear-ance and expressive movements reveal more than words. The retarded patient’s movements are slow, the limbs are rigid, the body is bent, and the expression is sad or anxious, and does not respond to the situation. The subjective feeling may be of emptiness, weak-ness, and tension. If the condition is severe, it can be difﬁ  cult to 
discriminate between depressive and catatonic stupor; patients 
with depressive stupor seldom have increased muscular tension or 
rigidity. Increased psychomotor activity can appear in depression as agitation, i.e. restlessness without the ability to attain goals or organize behaviour. In mania, increased psychomotor activity is also seen in sexual excesses and extravagant spending.
Psychomotor retardation, and probably also acceleration, may be 
accompanied by a changed experience of time.
(39) Depressed

(39) Depressed 
patients overemphasize the past, remembering guilt-connected events; manic patients feel that the future is immanent. Inability to distinguish wishes from reality results in poor decision-making in both depression and mania. Some depressives are unable even to decide how to dress in the morning. A manic patient’s workroom can reﬂ  ect the dissolution of his ability to give priority to impor-
tant things, for example tools for immediate and frequent use and those seldom used. Extreme retardation is seen in depressive stupor when patients do not move, speak, eat, or drink. Extreme accelera-tion occurs in mania (‘boiling over’) and may be accompanied by a sense of confusion.
Retardation and acceleration are closely related to depressive 
and manic thought disorder . In depression the ﬂ  ow of associations 
is reduced and slowed, and short-term memory can appear

is reduced and slowed, and short-term memory can appear 
impaired (pseudodementia). Depressed patients often ruminate 
about negative topics and have difﬁ  culty in terminating these 
thoughts. In mania, acceleration of thinking leads to a plethora of associations, ‘ﬂ  ight of ideas’ , and pressure of speech. Unlike patients 
with schizophrenic thought disorder, depressed patients retain logical connections.
Depersonalization  (see later) can occur alone or as part of a 
depressive state. In the latter, part of the body, the self, the mind, actions, or thinking are sensed as being alienated—not belonging to the self. In mood disorders, depersonalization does not usually reach the intensity of delusion, as it can in schizophrenia.
Although anxiety disorders and major depression have been 
deﬁ ned by operational criteria in the diagnostic manuals, the

deﬁ ned by operational criteria in the diagnostic manuals, the 
clinical symptoms of mood states vary considerably. Attempts have been made to deﬁ  ne a core syndrome by using factor analysis 
to identify latent trait symptom proﬁ  les derived from several 
assessment scales and from different samples of depressed patients. Cross-cultural comparisons of symptom proﬁ  les can also help to 
identify core symptoms. Among the latent traits, retardation was found most often, together with loss of interest and alteration of diurnal rhythm. Guilt, death wish, and affective reactivity occurred inconsistently.
(40)1.7 descriptive phenomenology

SECTION 1  the subject matter of and approach to psychiatry 56
Disorders of self and body image
Disorders of self
These describe the abnormal inner experiences of I-ness and 
my-ness which occur in psychiatric disorders. Scharfetter has added the characteristic of awareness of being or ego vitality to the four formal characteristics previously described by Jaspers: feeling of awareness of activity, awareness of unity, awareness of identity, and awareness of the boundaries of self.
(41,42)
(a) Disorder of the awareness of being
This is demonstrated by nihilistic delusions , which frequently 
occur in severe depressive illness and are a feature of the epony-mous Cotard’s syndrome.
(43) Non-psychotic abnormality is exem-
pliﬁ ed by depersonalization  in which the sufferer experiences his 
mental activity, body, or surroundings as changed in quality to become unreal, remote, or automatized.
(b) Disorder of awareness of activity

Disorder of the awareness of activity occurs with neurological lesions, such as some dyspraxias, and also in psychotic conditions in which the individual believes that no action has occurred when it has, or vice versa. This does not include action that the patient knows he has executed but with a belief it was under the inﬂ  uence 
of another. Non-psychotic disorder of activity occurs when an individual believes that he has no freedom of action and that his range of choice is limited by external circumstances, for instance a person with depressive symptoms who believes that he is inevitably incompetent.
(c) Disorder of awareness of singleness
In health, one assumes that ‘I am one person’ . Disorder occurs in the rare visual perceptual experience of autoscopy .
(44) Non-

(44) Non-
psychotic examples of disorder of singleness include the double phenomenon, described by Jaspers,
(45) and multiple personality 
disorder,  which is the apparent existence of two or more distinct 
personalities within an individual, only one of them being evident at any time. The double phenomenon  is much more frequent, and 
describes the self-experience of those who feel that there are two different parts of themselves in conﬂ  ict with each other; they are 
fully aware of both at the same time.
(d) Disorder of awareness of identity
Disorder of identity occurs in delusion of control  or passivity 
experience , in which the sufferer believes that he has been taken

experience , in which the sufferer believes that he has been taken 
over by an alien, with the belief that there is a break in continuity from ‘myself’ who was there before. Non-psychotic disorder of awareness of identity is exempliﬁ  ed by possession disorder , in 
which there is a temporary loss of the sense of personal identity and the individual may act as if they have been taken over by another 
personality, spirit, or force.
(e) Disorder of the awareness of boundaries of self
Disorder of boundaries of self occurs in ﬁ  rst-rank symptoms of 
schizophrenia such as thought withdrawal, control, and diffusion.(46)
The patient believes that thoughts ‘are being taken out of me, inﬂ  u-

enced by an outside source’ . Non-psychotic disorder of the bound-aries of self occurs in ecstasy states, characteristically described as an ‘as if’ experience. There is disturbance of boundaries of self in that the individual may feel that there is no limit between self and 
the outside world.
Depersonalization and derealization
Depersonalization is the experience of one’s own feelings and experiences being detached, distant, not one’s own, lost or altered. Derealization is the same range of subjectivity describing awareness of the outside world. The sufferer recognizes that this is a subjective change and is not imposed by outside forces. Because the sufferer ﬁ  nds it difﬁ  cult to describe, this experience tends to be

underdiagnosed, but the misery it causes and the disturbance in functioning is considerable; it is experienced as being so subjec-tively unpleasant that not uncommonly deliberate self-harm results.
Insight
The clinical assessment of a patient’s capacity to understand the nature, signiﬁ  cance, and severity of his or her own illness has been 
called insight. There is current interest in describing its characteris-tics and establishing how it correlates with other measures of illness.
(47) The attitude of patients towards their illness has clear

(47) The attitude of patients towards their illness has clear 
clinical implications, and the assessment of insight tries to investi-gate the patient’s awareness concerning the impact their illness has, and their capacity to adapt to the changes brought about by illness. The patient’s awareness of illness and the extent to which it is inter-fering with function affects compliance for prescribed treatment. David has proposed that insight implies the ability to relabel unusual mental events as pathological , the recognition that one has 
mental illness, and compliance with treatment. Some parallels have been drawn between the loss of insight in psychiatric patients and the denial of disease or loss of function that occurs in certain neurological conditions.
Because of its importance for clinical management, there have 
been many attempts over recent years to measure insight, all of which depend upon a precise operational deﬁ  nition of the concept. 
McEvoy et al.

(48) developed a questionnaire to measure the patients’ 
awareness of the pathological nature of their experiences and also their acceptance of the need for treatment. The measure constructed by David et al.
(49) added the ability to relabel unusual mental events 
as ‘pathological’ to the recognition of mental illness and compli-ance with treatment.
The relationship between impairment of insight and the pres-
ence of other aspects of psychopathology is complicated; there is no clear association between impairment of insight and intellectual or neuropsychological deﬁ  cit.
(50) Not surprisingly, patients with 
unimpaired insight are found to be signiﬁ  cantly less likely to 
require readmission to hospital, tend to be more compliant with treatment, and show an improved prognosis.
(51) Surprisingly, and

(51) Surprisingly, and 
this shows how little is known about this subject, many patients are prepared to comply with treatment, even though they do not believe themselves to be ill, if the social milieu is conducive to receiving treatment.
(48)
Insight is a multifaceted phenomenon with considerable clinical 
signiﬁ  cance as it predicts the likelihood of patients complying with 
treatment. Most studies of insight have been concerned with patients suffering from schizophrenia, and it is important to extend work to other serious mental illnesses.

57
Disorders of awareness of the body
(a) Bodily complaint without organic cause
Such conditions create difficulties for psychopathological 
understanding.
1 Aetiology is often obscure, sometimes with doubt that there may 
be an unrevealed physical cause.
2 The descriptive terms used come from different theoretical back-
grounds and have changed their meaning over the years.
3 There is often discrepancy between the meanings attached to the 
symptoms by the patient and by the doctor.
‘Somatoform disorders’ , which include both somatization and 
hypochondriacal disorders(52) are, characteristically, repeated 
presentation of physical symptoms with persistent requests for medical investigation, despite negative ﬁ  ndings, and reassurance by 
doctors that the symptoms have no physical basis. The patient with somatization  as the prominent disorder complains of multiple

doctors that the symptoms have no physical basis. The patient with somatization  as the prominent disorder complains of multiple 
recurrent, and often changing, physical symptoms in different bodily systems over a prolonged time. The patient with hypochon-
driasis  has a persistent preoccupation with bodily function, the 
possibility of illness, and the seriousness with which symptoms should be treated. Not infrequently these two groups of symptoms overlap. Co-morbid anxiety and depression is quite frequent with both somatization and hypochondriasis. The content of hypochon-driasis may take the form of delusion, overvalued ideas, hallucina-tion, anxious or depressive rumination, or anxious preoccupation.
The term ‘Dissociative (conversion) disorder’ has replaced the 
confusing, but graphic, hysteria. Conversion symptoms  can be

confusing, but graphic, hysteria. Conversion symptoms  can be 
categorized as motor, sensory (including pain), or psychological. Motor symptoms include weakness or paralysis of limbs or part of a limb and abnormality of gait; sensory symptoms include glove, and stocking anaesthesia. Amongst the psychological symptoms is a narrowing of the ﬁ  eld of consciousness with selective amnesia 
such as may occur in fugue states. For conversion disorder, or hys-teria, to be diagnosed, symptoms should appear to be psychogenic in nature, causation should be considered unconscious, symptoms may carry some sort of advantage to the patient, and they occur by the mediation of the processes of conversion or dissociation.
Artefactual illness  includes two categories: elaboration  of 
physical symptoms for psychological reasons, and intentional pro-duction or feigning  of symptoms or disabilities, either physical or

physical symptoms for psychological reasons, and intentional pro-duction or feigning  of symptoms or disabilities, either physical or 
psychological. Conversion symptoms are believed to arise without the patient’s conscious involvement, but artefactual illness implies that the illness, lesion, or complaint is ultimately the individual’s own conscious production. Malingering  implies feigning or pro-
ducing symptoms expressly for the social advantages of being regarded as ill, while the broader category of artefactual illness includes other motivations and simply describes the behaviour.
Narcissism  is an exaggerated concern with one’s self-image, 
especially with personal appearance. This absorption with self is usually associated with feelings of insecurity and ambivalence con-cerning the self and feelings of threat to one’s integrity.
Dislike of the body  and distortion of body image are subjectively

Dislike of the body  and distortion of body image are subjectively 
different experiences but often occur together, for example in anorexia nervosa or with gross obesity. In dysmorphophobia  the 
primary symptom is the patient’s belief that he or she is unattractive. Sufferers believe themselves to have a physical defect, such as the size of their nose or breasts, that is noticeable to other people, but 
objectively their appearance may lie within normal limits. The con-tent disorder of dysmorphophobia is an overvalued idea in which the degree of concern and consequent distress is clearly out of pro-portion and comes to dominate the whole of life. The overvalued idea of dysmorphophobia may be associated with an underlying personality disorder of anankastic or dependent type, or with other psychiatric disorders.
Awareness of body size  and disturbance of eating  frequently

Awareness of body size  and disturbance of eating  frequently 
occur together; alteration of body image is associated with eating disorder. Obesity in adolescence, in diet-conscious Western societ-ies, frequently results in self-loathing, more frequently in girls than boys, with overestimation of body fatness. Disturbance of body image occurs in sufferers from anorexia nervosa, characteristically 
an overestimate of width with an accurate estimation of height or the width of inanimate objects. The more ‘over-fat’ an individual 
considers herself to be, the more dissatisfaction with herself she will experience.
(53) Such disorders of self-image, with signiﬁ  cant 
overestimation of size and discrepancy between perceived and desired size, also occur in bulimia nervosa, and may be associated with depression of mood and feelings of guilt and unworthiness.
(b) Organic changes in body image

Organic change may result from either damage to the conceptual-ized object (e.g. following amputation, with a phantom limb) or damage to the process of conceptualization (e.g. section of the cor-pus callosum). Hyperschemazia, pathological accentuation of body image, occurs when physical illness or neurological lesion causes enhancement of perception of an organ. Diminished or absent body image (hyposchemazia, aschemazia) may occur with loss of innervation, or with parietal lobe lesions. The diminution of body image may be simple (e.g. loss or neglect of a limb) or complex. There may also be distortions of the body image (paraschemazia), in which enhancement or diminution of parts of the body may occur.
(c) Disorder of gender and sexuality
Core gender identity is established very early in life and then retained; it is biologically influenced and socially reinforced. Transsexualism  is a disorder of gender identity, much more com-

mon in biological males, in which there is discrepancy between anatomical sex and the gender that the person assigns to himself. The subjective belief is an overvalued idea. Other disorders of sexu-ality are considered elsewhere. (See Chapter 4.11.3)
(d) Pain as a psychopathological entity

Pain is a subjective experience, which is hard to describe and categorize; it is not well-charted phenomenologically. It appears to have more in common with mood than perception. Pain associated with psychiatric illness tends to be more diffuse and less well local-ized and to spread with non-anatomical distribution. It also tends to be complained of constantly, becoming even more severe at times but persisting without remission. It may clearly be seen to be associated with underlying disturbance of mood, which appears to be primary in time and causation. Psychogenic pain tends to progress in severity and extent over time. Persistent, severe, and distressing pain, which cannot be explained fully by a physiological process or physical disorder has been designated persistent 
somatoform pain disorder . (See Chapter 5.2.6.)1.7 descriptive phenomenology

SECTION 1  the subject matter of and approach to psychiatry 58
Motor symptoms and signs
Motor symptoms and signs may be due to a neurological disorder 
causing organic brain syndrome, such as rigidity in Parkinson’s disease, or may be related to emotional states such as restlessness or tremor in anxiety. However, there is a further group of symp-toms, which affect voluntary movements and often occur in functional psychoses. These symptoms are neither unequivocally neurological nor clearly psychogenic in origin and are termed motility disorder  by some authors. Table 1.7.1 gives a glossary of 
disordered motility. Whether patients are unable or unwilling to move normally is still a matter of debate. The origin of motility symptoms may well be a functional (rather than a morphological) abnormality of basal ganglia.
A further classiﬁ  cation of motility disorder distinguishes psy-

chomotor hyperphenomena (e.g. tic disorder), hypophenomena (e.g. stupor), and paraphenomena (e.g. mannerism). Tics are rapid, 
irregular movements involving groups of facial or limb muscles. Stupor  is a state in which a patient does not communicate, i.e. does 
not speak (mutism) or move (akinesia), although he or she is alert. Mannerisms  are uncommon; they are conspicuous expressions by 
gesture, speech, or objects (e.g. dress) that seem to have a particular meaning, often delusional.
Catatonia  is a psychopathological syndrome of disturbed motor 
behaviour. It is generally reversible, and it occurs with mood disor-ders, general medical conditions, toxic and psychotic states, and 
neurological disorders. Brain tumour, encephalitis, endocrine, and

neurological disorders. Brain tumour, encephalitis, endocrine, and 
metabolic disorders may elicit catatonic symptoms. In Western countries catatonia is considered, nowadays, to be uncommon in general psychiatric practice, however, some catatonic symptoms have been found to occur in 5–10 per cent of acute psychiatric in-patients.
(54)Stupor ,mutism , and negativism  are the classical triad of symp-
toms demarcating the catatonia syndrome, and automatic obedi-ence and stimulus-bound behaviour, stereotypy, and catalepsy contribute to the syndrome in manic patients.
(55) Lesser symptoms 
may occur, and catatonia may take the form of hypomobility, with stupor only in extreme cases. Patients in stupor remain persistently unresponsive for hours, days, or even longer. They appear to be unaware of events around them and are mute.
Catatonic excitement presents as excessive motor activity. Such 
patients may talk incessantly, especially when in an ‘exalted stage’ .
(56)

(56)
There may be outbursts of talking, singing, dancing, and removing their clothes. Such states carry the risk of exhaustion, dehydration, and injury; it may be harmful and dangerous to the patient and to others.
In negativism  the patient resists the examiner’s manipulations 
with force equal to that applied by the examiner. In catalepsy  (pos-
turing), the patient maintains posture for long periods. These include facial postures, such as grimacing or schnauzkrampf  (lips in 
a pucker); body postures, such as psychological pillow  (lying on his 
back with head elevated as if on a pillow); lying in a ‘jack-knife’ posi-tion; and many other uncomfortable and bizarre postures main-tained against gravity or attempts to rectify them. An examiner trying to move a cataleptic limb passively will notice waxy ﬂ  exibility , in

which initial resistance to an induced movement changes to gradu-ally allowing the imposition of a posture, like bending a candle.
Stereotypy  is non-goal directed, repetitive behaviour, the verbal 
form of which is called verbigeration , endless repetition of phrases 
and sentences. Automatic obedience  occurs when, despite instruc-
tions to the contrary, the patient permits the examiner to move his limbs into a new posture. This may then be maintained against instructions to the contrary. In ambitendency  the patient appears 
stuck in indecisiveness, resisting the examiner’s non-verbal signals, but showing hesitancy in doing so.
Echo phenomena  may occur when the patient is interacting 
with another person and present as echolalia  (imitation of the 
speech of others) or echopraxia  (imitation of the actions of others). 
Mannerisms  are strange but purposeful movements characteristic 
of that person. They may be exaggerated caricatures of ordinary movements.

Disordered speech  may also be regarded as a sign of disordered 
motility, as in mutism or verbigeration.
In delirium , tremor often occurs. Anxiety is accompanied by 
restlessness. In a particular motor pattern in delirium tremens (alcohol withdrawal delirium) the patient appears to be collecting objects or brushing away dust. Typically, the movements never seem to achieve what they are meant to and, of necessity therefore, are repetitive. Suggestibility in delirium may lead to movements, which are based on erroneous assumptions, such as trying to take hold of a proffered, but non-existent, thread. Patients may develop panic and try to ﬂ  ee. Speech may be hurried and indistinct. In some 
cases of delirium, such as that due to hepatic failure, patients may 
be hypoactive before becoming drowsy and comatose. Hepatic

be hypoactive before becoming drowsy and comatose. Hepatic 
failure may also result in catatonic disorder.
Many conditions, such as brain tumour, encephalitis, and endo-
crine and metabolic disorders, may elicit catatonic symptoms. Patients with a variety of mental disorders may show abnormal movements that are of histrionic nature. They may throw themselves to the ground, seek and maintain bodily contact, or show psychomo-tor agitation. Alternatively, there may be psychogenic paresis.Table  1.7.1  Symptoms and signs of motility disorder
Catalepsy (synonym; waxy 
ﬂ  exibility, ﬂ  exibilitas cerea)Maintaining uncomfortable positions against 
resistance
Posturing Maintaining uncomfortable positions that may 
have a delusional meaning

Stupor Inability to communicate despite being awakeAkinesia Inability to moveMutism Inability to speakEcholatia Repetition of another person’s speechEchopraxia Repetition of another person’s actsMannerism Uncommon conspicuous expression by 
gestures, speech, or objects
Grimacing Uncommon conspicuous facial expressionStereotypy Repetition of actionsVerbigeration Repetition of speechTic Rapid movements of facial or limb musclesAkathisia Inability to remain seated or standingPsychomotor retardation Slowing of mental and motor activityPsychomotor agitation Arousal of mental and motor activity (typically 
by anxiety)

59
In dementia there may be general disturbance of psychomotor 
functions leading to disturbed co-ordination and clumsiness. During the further progress of dementia, lethargy, and akinesia may occur.
Sequelae of encephalitis are known to include a number of 
motor symptoms apart from parkinsonism, as seen in the epidemic of encephalitis lethargica that occurred around 1920. Ta r d i ve 
dyskinesia  is a side-effect of neuroleptic therapy. However, since 
signs of tardive dyskinesia such as perioral hyperkinesia and dysto-nias were described before the introduction of neuroleptics,
(57) it is 
also a motor symptom of mental disorder in its own right.
Disorders of memory
The psychology of memory is discussed in Chapter 2.5.3.
Memory may be differentiated into short-term or recent memory

Memory may be differentiated into short-term or recent memory 
and long-term or remote memory. Furthermore, ultra-short-term memory may be distinguished from short-term memory. Ultra-short-term memory encompasses immediate registration within the span of attention. Short-term memory reﬂ  ects new learning. 
Long-term memory is usually associated with earlier data or other information that has been stored for months or years.
Additional terms describing memory functions are declarative
and procedural  memory. Declarative memory contains facts, which 
may be consciously recalled, whereas procedural memory contains skills and automatic activities. In dementia—both degenerative (Alzheimer type) and vascular (multi-infarct dementia)—recent memory is usually impaired earlier than remote memory.
Biographical memory is the recall of events in a person’s past,

Biographical memory is the recall of events in a person’s past, 
which have an emotional loading, and therefore an impact on 
understanding depression.
Amnesia is a period of time, which cannot be recalled, and it may 
be global or partial. With regard to time it may be retrograde—an expression derived from the idea that one is looking backwards from an event (such as brain trauma or electroconvulsive therapy) to ﬁ nd the period that is deleted before the event. Correspondingly, 
anterograde amnesia means a period of deleted memory after an event. Although it is difﬁ  cult to distinguish between types of 
amnesia, focal lesions in the hippocampus seem to affect remote memory less than recent memory, whereas diffuse brain disease often affects both. In psychogenic amnesia it is sometimes possible to recognize speciﬁ  c personal meaning in the events which cannot 
be recalled.
(58) Amnestic disorders should strongly alert the 
examiner to the possibility of cerebral pathology.

Disorders of memory are closely connected with other disorders, 
such as disorders of consciousness; there is often amnesia for episodes of disturbed consciousness.
Some patients are aware of memory disorder and complain 
about it; others tend to neglect their memory deﬁ  cits and manifest 
secondary signs such as confabulation. Confabulations are inven-tions, which substitute for missing contents in gaps of memory; the patient is not aware that they are not true memories.
A disorder of short-term memory, as in Korsakoff’s syndrome or 
transient global amnesia, is often neglected by the patient. Behaviour appears normal, and it often seems that the personality is intact. Such a patient may be engaged in lively conversation or 
seemingly purposeful actions, and only after further investigation

seemingly purposeful actions, and only after further investigation 
does it become obvious that these activities are not based on facts. This memory disorder can be assessed directly by examining the patient. Other forms become apparent retrospectively on taking 
the patient’s history. In these cases the patient complains about 
periods of global or partial amnesia. Memory for certain events may have faded or become obscured by layers of other events (palimpsest); this is typical of repeated amnestic periods following bouts of drinking. In mood disorder there may be complaints about impaired memory, although no memory deﬁ  cit is found in 
objective tests. Examples of false memory (paramnesia) are déjà vu ,
an erroneous feeling of familiarity with, for example, a person or a room, and jamais vu, a feeling of unfamiliarity for a well-known object. Déjà vu  may occur in temporal lobe epilepsy, although it 
is not speciﬁ  c for that disorder. Delusional memories are also

is not speciﬁ  c for that disorder. Delusional memories are also 
examples of paramnesia.
Disorders of consciousness
Consciousness is the sum of various mental functions—in the words of Jaspers
(59) ‘the whole of present mental life’ . Lipowski,(60)
who regards the concept of consciousness to be ‘completely redun-dant’ , describes what is commonly meant by clouding of conscious-ness on the basis of a number of behavioural features (Table 1.7.2). In contrast with Lipowski, the concept of consciousness has recently elicited fresh interest in philosophy and clinical neurology. (See Chapter 2.1)
Consciousness is a mode of relatedness between mind and world. 
Disordered consciousness may occur on a dimension of severity, which ranges from lucidity via clouding and then towards uncon-sciousness. The latter represents a state of coma. In addition, consciousness may be assessed on a dimension of vigilance.
(61)
Ey(62) regards consciousness as an attribute of wakefulness. Indeed,

(61)
Ey(62) regards consciousness as an attribute of wakefulness. Indeed, 
sleepiness implies a reduction in consciousness; but consciousness may also be reduced despite normal vigilance. Likewise, con-sciousness is impaired by a disorder of memory, orientation, or coherence, as in the clouded consciousness of delirium.
When consciousness is impaired there is clouding of perception, 
ideas, and images. The intensity of perception is diminished and there is a disintegration of order in the perceptive ﬁ  eld. Accordingly, 
patients become disoriented.
The term ‘confusional state’ is a synonym for delirium that 
emphasizes thought disorder and disorientation. Disorientation
may concern time, place, or person. T emporal and geographical disorientation are common. Remote contents are better remem-bered than recent ones; name or date of birth is usually more available than age, or name of the hospital. It is useful, after a polite

excuse, to ask direct questions concerning orientation, even if they 
sound trivial, since some patients are skilful in avoiding topics that show the degree of their disorientation.
Table 1.7.2  Behavioural features indicating clouding of 
consciousness
The person is awake but may be drowsy
Awareness of the self and the environment is reducedBoth immediate and recent memory are impairedThinking is disorganized, and may be dreamlike; for instance perception is 
faulty and misperceptions may occur
The ability to (learn new material is reduced) learnThe person is unable to overcome this state by deliberate effort1.7 descriptive phenomenology

SECTION 1  the subject matter of and approach to psychiatry 60
Another abnormality is described by the term narrowing of 
consciousness , which means that awareness of a person’s environ-
ment is restricted, for example, owing to an abnormal affective or delusional state.
In epileptic aura or after taking certain drugs, consciousness 
may be experienced as heightened with increased intensity of awareness.
Twilight state  is a well-deﬁ  ned interruption of the continuity of 
consciousness. Consciousness is clouded and sometimes narrowed. Despite the disorder of consciousness, the patient is able to per-form certain actions, such as dressing, driving, or walking around. Subsequently, there is amnesia for this state. Twilight states may occur in epilepsy, alcoholism ( mania à potu  is a twilight state), 
brain trauma, general paresis, and dissociative disorder. Mania à 
potu  describes the situation where a person reacts excessively by

potu  describes the situation where a person reacts excessively by 
developing twilight state with small amounts of alcohol. Often these patients have an increased vulnerability due to pre-existing organic brain pathology. Twilight state occasionally leads to violent behaviour.
In an oneiroid state  the patient experiences narrowing of con-
sciousness together with multiple scenic hallucinations. Oneiroid states may occur in schizophrenia, but are also observed in patients who have to be totally passive and dependent on others. The atmo-sphere is perceived as strange and dreamlike. Accordingly patients may be aloof and behave like dreamers.
(63) Unlike twilight states, 
the contents of oneiroid states are often remembered.
Disorders of attention and concentration

Attention and concentration imply the directing of mental activities towards a particular object. Attention is associated with present alertness, and concentration with longer lasting achievement and performance; there is a distinction between selective  and shared
attention. Attention and concentration may be impaired by clouded consciousness or individual aspects, such as sleepiness, incoher-ence, or memory deﬁ  cit. However, there may be other reasons for 
inattention such as hallucination or mood disturbances. Attention deﬁ cit is a permanent feature in the childhood disorder, attention-
deﬁ cit hyperactivity disorder.
Assessment of attention and concentration may consist of simple

Assessment of attention and concentration may consist of simple 
arithmetical tasks and include psychometric performance test in addition to the clinical examination. Psychometric performance tests are also valuable tools in assessing disorder of memory and 
consciousness.
Disorders of sleep  are described in Chapter 4.14.
Disorder of personality
It is the expression of disordered personality which is the consider-
ation of descriptive phenomenology, the observation of character-istic behaviour and the subject’s self description. Schneider has deﬁ ned personality as ‘the unique quality of the individual, his 
feelings and personal goals’
(64)Abnormality of personality  is present 
when a characteristic or trait of clinical relevance is developed in 
the patient to a statistically abnormal extent, that is either deﬁ  cient 
or excessive. Personality disorder  is present when that abnormality

or excessive. Personality disorder  is present when that abnormality 
causes suffering to the patient or to other people. A person with antisocial personality disorder not uncommonly causes discomfort to other people; with obsessive-compulsive personality disorder the abnormal characteristics may frequently cause distress to the 
individual himself.
Both ICD 10 and DSM-IV are derived from Schneider’s des-
cription of personality types. The advantage of such a typological approach is that it does not imply any speciﬁ  c theory of causation.

cription of personality types. The advantage of such a typological approach is that it does not imply any speciﬁ  c theory of causation. 
The accurate description of personality characteristics and type is valuable in clinical practice for diagnosis, prognosis and the rational planning of treatment. The skills of psychopathology are ideally suited to the observation of consistent personality traits, and forming an opinion unprejudiced by preconceived theoretical considerations. Descriptions of different personality types and disorders are developed elsewhere.
This revised chapter, prepared by Andrew Sims, is based on that in the ﬁ  rst edition by Andrew Sims, Christoph Mundt, Peter Berner, 
and Arnd Barocka. The contributions of these authors to the origi-nal text is gratefully acknowledged.
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M.W. Hamilton, 1958). Cassell, London.1.7 descriptive phenomenology

1.8
Assessment
Contents
 1.8.1. The principles of clinical assessment 
in general psychiatry
 1.8.2 Assessment of personality
 1.8.3 Cognitive assessment
 1.8.4 Questionnaire, rating, and behavioural methods of assessment
1.8.1. The principles of clinical 
assessment in general psychiatry
This chapter is focused on the needs of the clinician in a service

This chapter is focused on the needs of the clinician in a service 
for general adult psychiatry, who has to carry-out the initial assessment of the patient and family, working either in the con-text of a multi-disciplinary team or independently. Within this quite wide remit, the discussion is limited to general principles that guide the practice of all types of psychiatry. The chapter does not include the special procedures and techniques also needed for assessment of children and adolescents, the elderly, persons with mental retardation, persons with forensic problems, and persons requiring assessment for suitability for special types of psychotherapy.
It is assumed that the reader has already had signiﬁ  cant experi-
ence of clinical psychiatry and has completed the ﬁ  rst stages of

ence of clinical psychiatry and has completed the ﬁ  rst stages of 
a postgraduate psychiatric training programme. Therefore details of the basic methods recommended in commonly used textbooks 
or manuals of instruction for obtaining and recording information on essentials such as the history, personal development, mental state, and behaviour of the patient are not included in this chapter.
(1)
Three topics have been given special attention. These are assess-
ment by means of a multi-disciplinary team , the trio of concepts 
diseases, illness, and sickness , and the development of structured 
interviewing and rating schedules . The ﬁ  rst two have a special 
connection that justiﬁ  es emphasis in view of the recent increase in

connection that justiﬁ  es emphasis in view of the recent increase in 
multi-disciplinary styles of assessment. For instance, when differ-ent members of the team appear to be in disagreement about what should be done, it is usually a good idea to ask the question: ‘What is being discussed—is it the patient’s possible physical disease, the patient’s personal experience of symptoms and distress, or the interference of these with social activities?’ It will then often become apparent that the issues in question are legitimate differences in emphasis and priority of interest, rather than disagreements. The third topic is given prominence in order to illustrate some aspects of the background of the large number of such schedules (or 
‘instruments’) that are now available. They are usually given the

‘instruments’) that are now available. They are usually given the 
shortest possible mention in research reports, but since most advances in clinical methods and service developments come from studies in which an assessment instrument has been used, 
clinicians should know something about them.
The aim of the initial clinical assessment is to allow the clinician 
and team to arrive at a comprehensive plan for treatment and management that has both short-term and longer-term components. The achievement of this will be discussed under the following headings.
◆ Concepts underlying the procedures of assessment
◆ Contextual inﬂ  uences on assessment procedures
◆ Assessment as a multi-disciplinary activity
◆ Instruments for assessment
◆ The condensation and recording of information
◆ Making a prognosis
◆ Reviews
◆ Writing reports

63
Concepts underlying the procedures 
of assessment
The separation of form from content, and from 
effects on activities
In psychiatric practice more than in other medical disciplines, 
the key items of information that allow the identiﬁ  cation of signs 
and symptoms of psychiatric disorders are often embedded in a mixture of complaints about disturbed personal and social rela-tionships, together with descriptions of problems to do with work, housing, and money. These complaints and problems may be a contributing cause or a result of the symptoms of psychiatric disorders, or they may simply exist in parallel with the symptoms. A preliminary sorting out into overall categories of information is therefore essential.
The distinction between the form and the content of the symp-
toms is particularly important, together with the differentiation of both of these from their effects upon the functioning of the patient 
(function is used here in a general sense as applying to all activities,

(function is used here in a general sense as applying to all activities, 
in contrast to the speciﬁ  c meaning given to it in the classiﬁ  cation 
of disablements). This differentiation is discussed in Chapter 1.7, so only a brief mention is needed here.
The presenting complaint of the patient is often the interference 
with functions, but enquiry about the reasons for this should then reveal the contents of the patient’s thoughts and feelings. The form of the symptoms (i.e. the technical term, such as phobia or delusion used to identify a recurring pattern of experience or behaviour known to be important) allows the identiﬁ  cation of the 
psychiatric disorder. Knowledge of the effects on functions is essen-tial for decisions about the management of patient and family, and is an important aspect of the severity of the disorder.
This sorting into different types of information often implies 
a conﬂ  ict of priorities during the interview. The clinician must

a conﬂ  ict of priorities during the interview. The clinician must 
be seen to acknowledge the concerns and distress of the patient, but also must ask questions that will allow the identiﬁ  cation of 
symptoms. Learning to balance this conﬂ  ict of interest is an essen-
tial part of clinical training, and has been well recognized by previ-ous generations of descriptive psychiatrists, including Jaspers. The separation of the social effects of a symptom from the symptom itself is also a necessary part of the assessment process. Further comments on this and related issues have been made by Post
(2) and 
by McHugh and Slavney.(3)
Categories of information: subjective, objective, 
and scientiﬁ  c
Is there such a thing as a truly objective account of events? If

(2) and 
Is there such a thing as a truly objective account of events? If 
‘objective’ is intended to mean absolutely true and independent of all observers, the answer must be negative. Students and trainee psychiatrists often come to psychiatric clinical work from medical and surgical disciplines where they have been encouraged to ‘search for the facts’ with the implication that ‘true’ facts exist. They may need to be reminded that the supposed facts of all medical histo-ries, even those of clearly physical illnesses, depend upon the perceptions, opinions, and memories of individuals who may give different versions of the same events at different times.
‘Objective’ has several shades of meaning in ordinary usage, but

‘Objective’ has several shades of meaning in ordinary usage, but 
in clinical assessment it’s most useful meaning is that an account of an event or behaviour is based on agreement between two or more persons or sources. In contrast, ‘subjective’ can be used to indicate 
that the account comes from only one person. Objective informa-tion is likely to be safer to act upon than subjective, so efforts should always be put into raising as much as possible of the infor-mation about a patient into the objective category. Nevertheless, many of the most important symptoms in psychiatry can only be subjective, since they refer to the inner experience of the one 
person who can describe them.
When assessing the reliability and usefulness of other types 
of information, such as the results of treatment or possible expla-nations of causes, a further useful distinction can be made between objective deﬁ  ned as above and ‘scientiﬁ  c’ , taking this to mean that

systematic efforts have been made to obtain evidence based upon comparisons (or ‘controls’) which demonstrate that one explana-tion can be preferred out of several possibilities that have been considered.
Simple deﬁ  nitions such as these are useful in clinical discussions, 
but it must be remembered that in the background are many complicated and unsolved problems of philosophy and semantics. Some of these suggestions on the status of information in clinical work are based upon the writings and clinical teaching of Kraupl Taylor.
(4)
Disease, illness, and sickness
These concepts have existed in the medical and sociological literature for many years, and are best regarded as useful but inexact concepts that refer to different but related aspects of the person affected, namely pathology (disease), personal experience (illness), and social consequences (sickness), respectively.
(5) They

(5) They 
are useful as a trio because they serve as a reminder that all three levels should be considered in a clinical assessment, even though for different patients they will vary greatly in relative importance. There are no simple answers to questions about how they are best deﬁ ned and how exactly they are related to each other, but time 
spent on these issues is not wasted because they reﬂ  ect quite 
naturally some of the different interests and priorities of the differ-ent health professions (and are therefore often the basis of different viewpoints put forward by various members of a multi-disciplinary team).
Another reason for being familiar with these concepts is that 
in legal and administrative settings, simple and categorical pro-nouncements about the presence of mental illness or mental 
disease and their causes and effects may be required whatever 
the medical viewpoint might be about the complexity of these concepts.

Clinicians of any medical discipline know from everyday experi-
ence that the complete sequence of disease—illness—sickness does not apply to many patients. Although disease usually causes the patient to feel ill and the state of illness then usually interferes with many personal and social activities, in practice there are many exceptions. Potentially serious physical, biochemical, or physiologi-cal abnormalities (disease) may be discovered in surveys of apparently healthy persons before any symptoms, distress, or inter-ference with personal activities (illness) have developed, and some patients may have either or both of illness and sickness (interfer-ence with social activities) without any detectable disease.
A number of sociologists, anthropologists, and philosophers 
have joined psychiatrists in trying to deﬁ  ne mental illness and

have joined psychiatrists in trying to deﬁ  ne mental illness and 
mental health, but without achieving much clariﬁ  cation. Aubrey 1.8.1 the principles of clinical assessment in general psychiatry

SECTION 1  the subject matter of and approach to psychiatry 64
Lewis(6) and Barbara Wootton,(7) although writing from the differ-
ent contexts of clinical psychiatry and sociology, both arrived at the conclusion that neither mental illness nor mental health could be given precise deﬁ  nitions, although they are useful terms in every-
day language (and the same applies equally to physical health and physical illness).
More positive conclusions have resulted from attempts to deﬁ  ne 
disease, in that Scadding (a general physician) has suggested that it should be deﬁ  ned as an abnormality of structure or function that 
results in ‘a biological disadvantage’ .
(8,9) This seems reasonable if

(8,9) This seems reasonable if 
one is dealing only with conditions that have a clear physical basis, but if applied in psychiatry it implies that, for instance, behaviours such as homosexuality that reduce the likelihood of reproduction would have to be regarded as diseases alongside infections, carcinoma, and suchlike. This seems to be stretching a traditional concept too far, and different approaches clearly need to be explored.
One way forward is to accept that simple deﬁ  nitions and con-
cepts encompassed by one word cannot cope with complicated ideas such as disease or health, and to take care to differentiate between deﬁ  nitions of these as concepts in their own right, and 
attempts to develop models of medical practice . The debate noted 
above refers to concepts of health, disease, and disorder, and it has been continued more recently with respect to psychiatry in two 
quite extensive reviews, in terms of the types of concepts,

(10) and of 
their possible contents.(11) What follows below is better regarded as 
about models of medical practice , and two points are suggested as a 
basis for the discussion. First, more than one dimension or aspect of the person affected always needs to be included in descriptions of health status. Second, models of medical practice and thinking do not necessarily have to start with the assumption that physical abnormalities (diseases) are the basic concept from which all others are derived.
Regarding the ﬁ  rst point (of more than one aspect or dimen-
sion), soon after the contribution of Susser and Watson
(5) noted 
above, Eisenberg, a psychiatrist with social and anthropological interests,
(12) made a plea for all doctors, but particularly psychia-

(5) noted 
trists, to recognize the importance of appropriate illness behaviours in addition to giving the necessary attention to the diagnoses and treatment of serious and dangerous disorders.
(13) He gave special 
emphasis to the need to minimize problems that may arise from discrepancies between disease as it is conceptualized by the physi-cian and illness as it is experienced by the patient: ‘when physicians dismiss illness because ascertainable disease is absent, they fail to meet their socially assigned responsibilities’ . A similar model with a more overtly three-dimensional structure usually referred to as ‘bio-psychosocial’ has also been described by Engel.
(14) and also by 
Susser.(15) Historically, all these can be regarded as variations on 
and explicit developments of a theme that has been accepted

and explicit developments of a theme that has been accepted 
implicitly by generations of psychiatrists inﬂ  uenced by the ‘psycho-
biology’ of Adolf Meyer and his many distinguished pupils, mani-fest in the importance given to the construction of the traditional clinical formulation.
The second point, to do with the disease level not being the best 
starting point for conceptual models of medical practice, is of more recent and speciﬁ  cally psychiatric origin. Both Kraupl Taylor
(16)
and, more recently, Fulford(17) give detailed arguments for the con-
clusion that the illness experience of the patient is the most satis-factory starting point from which to develop a model of medical practice. Taylor presents his case as a matter of logic, and Fulford 
works through lengthy philosophical and ethical justiﬁ  cations. This

works through lengthy philosophical and ethical justiﬁ  cations. This 
new viewpoint has the virtue of starting with the encounter between patient and doctor, which has the strength of being one of the few things that is common to all types of clinical practice. In Taylor’s terms, by describing symptoms and distress the patient arouses ‘therapeutic concern’ in the doctor and so ﬁ  rst establishes 
‘patienthood’ . Whether or not a diagnosis is reached or a disease is later found to be present, and whether or not the social activities of the patient are also interfered with, are other issues of great impor-tance, but they do not diminish the primary importance of the ﬁ  rst 
interaction; in this, both patient and doctor play their appropriate roles according to their personal, social, cultural, and scientiﬁ  c 
backgrounds.
If medical training and practice are guided by this model, there

If medical training and practice are guided by this model, there 
is no interference with the essential obligation of the doctor to identify and treat any serious disease that may be present. However, a parallel obligation to satisfy the patient and family that the illness (comprising complaints and distress) and the sickness (interfer-ence with activities) have also been recognized and will be given attention, is equally clear.
How to answer questions by the patient and family about wheth-
er the patient has a mental illness or not, and what this implies, needs careful discussion. Within a multi-disciplinary team it is usu-ally best for the team to reach early agreement on a particular way of describing the patient’s illness so that conﬂ  icting statements will

not be made inadvertently by different members if asked about it. This is because the patient or family may expect this type of state-ment, and not because distinctions between, for instance, mental illness and physical illness, or between nervous illness and emo-tional upset, are regarded as fundamental from a psychiatric view-point. This difﬁ  cult issue will be made easier if something about 
the patient’s ideas about the nature and implications of terms such as ‘mental illness’ and ‘nervous breakdown’ is always included as part of the initial assessment information. Similarly, all members of the team need to be familiar with the concept of illness behav-iour and the way this is determined by cultural inﬂ  uences
(18) (see 
Chapter 2.6.2).
The diagnostic process: disorders and diagnoses

(18) (see 
Psychiatrists learn during their general medical training that the search for a diagnosis underlying the presenting symptoms is one of the central purposes of medical assessment. This is because if an underlying cause can be found, powerful and logically based treat-ments may be available. But even in general medicine, as Scadding pointed out ‘the diagnostic process and the meaning of the diagno-sis which emerges are subject to great variation . . . the diagnosis which is the end-point of the process may state no more than the resemblance of the symptoms and signs to a previously recognized pattern’ .
(8,9) In psychiatry, ‘may’ becomes ‘usually’ , and this has been 
recognized by the compilers of both ICD-10 and DSM-IV , in that these are presented not as classiﬁ  cations of diagnoses, but of disor-
ders. These classiﬁ  cations use similar deﬁ  nitions of a disorder; the

ders. These classiﬁ  cations use similar deﬁ  nitions of a disorder; the 
key phrases in ICD-10 are ‘the existence of a clinically recognizable set of symptoms or behaviour associated in most cases with dis-tress and with interference with personal functions’ , and in DSM-IV ‘a clinically signiﬁ  cant behavioural or psychological syndrome 
or pattern that occurs in an individual and that is associated with present distress or disability . . . ’ .

65
The use of such broad deﬁ  nitions is necessary because of the 
present limited knowledge of the causes of most psychiatric disor-ders, and a similarly limited under standing of proc esses that un derlie 
their constituent symptoms. T o avoid overoptimistic assumptions, there is much to be said for psychiatrists avoiding the use of the term ‘diagnosis’ except for the comparatively small minority of instances in which it can be used in the strict sense of indicating knowledge of something underlying the symptoms. A consequence of this viewpoint is that the currently used ‘diagnostic criteria’ in both these classiﬁ  cations should be relabelled as ‘criteria for the 
identiﬁ  cation of disorders’ .
In spite of this, it must be accepted that the patient and family

In spite of this, it must be accepted that the patient and family 
are likely to expect statements to be made about the cause of their distress and symptoms. The members of all human groups expect their healers to discover the causes of their misfortunes (i.e. to make a diagnosis), and to provide remedies. This is so whether the group is a sophisticated and scientiﬁ  cally oriented modern society, 
or a non-industrialized society that relies on ethnic healers and folk remedies. The obvious relief of a patient or family on the pro-nouncement of an ‘ofﬁ  cial’ diagnosis is often evident in any type of 
healing activity, even though the diagnostic terms themselves mean very little. The pronouncement of an ofﬁ  cial diagnosis is taken to

healing activity, even though the diagnostic terms themselves mean very little. The pronouncement of an ofﬁ  cial diagnosis is taken to 
show that the doctor knows what is wrong, and therefore will be able to provide successful treatment or advice. If the diagnosis is expressed in terms that the patient can understand, it will have additional power as an explanatory force.
The readiness of ethnic healers and practitioners of complemen-
tary (or alternative) medicine to provide a diagnosis and treatment 
in terms that have a meaning and therefore a powerful appeal to their customers is probably one of the main reasons for their con-tinued survival and popularity alongside scientiﬁ  cally based medi-
cine. This is a separate issue from the question of whether or not the treatments of complementary practitioners are successful in the sense of having effects that could be demonstrated by means of a controlled clinical trial.
Within psychiatry and clinical psychology, the medical habit of

Within psychiatry and clinical psychology, the medical habit of 
searching for a diagnosis has at times been misunderstood as an unjustiﬁ  ed preoccupation with the presence of physical disease as a 
cause of mental disorders. This was most marked in the United States during the 1950s and 1960s, expressed particularly in the writings of Menninger in which the diagnostic process and attempts to classify patients were dismissed as a waste of time.
(19) This view-
point ignores two points made here and by many others; ﬁ  rst, the 
choice of a diagnostic term is only one part of the overall process of assessment that leads also to a personal formulation. Second, any assessment of a person, whether made as statements about psycho-dynamic processes, as statements about structural and biochemical abnormalities, or as statements about interference with activities, is unavoidably an act of classiﬁ  cation of some sort.
More detailed discussions about the importance of diagnosis

More detailed discussions about the importance of diagnosis 
have been provided by Scadding
(8) as a general physician, and by 
Kendell(20) and Cooper.(21) as psychiatrists.
Concepts of disablement
Disablement will be used here as an overall term to cover any type of interference with activities by illness. This is often of more con-cern to the patient than the symptoms of the illness itself, since the fear of long-term dependence upon others is usually present, even though not voiced in the early stages. The question arises whether to leave the description and assessment of disablement to different 
members of the team as it arises in various forms, or whether in addition to encourage reference to one of the systematic descriptive schemes that are now available. Even if not used as fully as their authors intend, these have the merit of serving as checklists or reminders for the whole team, to ensure that the many different effects of the illness have been considered.

Two widely used descriptive schema are the International 
Classiﬁ  cation of Functioning, Disability and Health  (ICF),
(22) and a 
broadly similar framework described by Nagi(23) that is often used 
in the United States, particularly by neurologists. These are best regarded as descriptive conceptual frameworks rather than classiﬁ  -
cations, sharing a basic structure of several levels of concepts. For the ICIDH, these are functioning ,disability , and the contextual 
factors (both environmental and personal)  relevant to what is 
being assessed. These terms and concepts are deﬁ  ned in the manu-
als published by WHO Geneva. The ICF is published as both a short and a long version, and it is probably wise for interested users to start by examining the short version. As noted in Fig. 1.8.1.1, these three concepts can be put alongside the sequence of ideas that leads from complaints, through symptoms to the identiﬁ  cation of

disorders or diagnoses. This may represent a causal sequence in some individuals, and this is clearest in acute physically based ill-nesses. But for many patients encountered in psychiatric practice, 
whose illnesses often have prominent social components, causal 
relationships may be absent or even in the opposite direction. For instance, sudden bereavement, i.e. loss of a social relationship, may be the clear cause of interference with the ability to perform daily activities (disability), and also of uncontrolled weeping (an impairment of the normal control of emotions). Social handicaps can also be imposed unjustiﬁ  ably by other persons, as when a 
patient who is partly or fully recovered from long-standing psychi-atric illness and quite able to work is refused employment due to the prejudice of a potential employer.
Many mental health workers ﬁ  nd that to use a scheme such as

Many mental health workers ﬁ  nd that to use a scheme such as 
Fig. 1.8.1.1 or the ICF helps to clarify how different aspects of a patient’s problems ﬁ  t together. Similarly, the different members of 
the team may be able to see more clearly how their activities with the patient and family complement one another, since the different concepts in the framework correspond approximately with the interests of different health disciplines. Social workers will focus on assessment of work and social relationships, occupational thera-pists will have a special expertise in the assessment of daily activi-ties, and clinical psychologists are skilled in the assessment of cog-nitive and other psychological functions. Researchers in the various health disciplines have naturally devised rating scales that reﬂ  ect

their own interests and ideas, independently of the ICF or other overall schema, but it is usually found that such scales correspond quite closely with one or other of the concepts just discussed. 
The reluctance of both researchers and clinicians to adopt a 
standard set of terms to cover the various levels or concepts contin-ues to be a problem; the reader needs to be aware that the terms 
impairment, disability, and handicap are often used synonymously 
by different authors.
The description of social and interpersonal relationships is 
in principle included in comprehensive schemas such as the ICF and that of Nagi, but many separate instruments that cover relationships in great detail have been devised over the years by psychotherapists, family therapists, and others.
(24–26)1.8.1 the principles of clinical assessment in general psychiatry

SECTION 1  the subject matter of and approach to psychiatry 66
The sequence of assessment: collection, analysis, 
synthesis, and review
As information accumulates and is discussed, several different but 
related aspects of the patient and the illness have to be kept in 
mind. Good psychiatric practice is a part of what is sometimes 
referred to as ‘whole-person medicine’ in which at different times 
the contrasting but complementary processes of both analysis and 
synthesis of the information available will be needed. The patient 
must be seen both as an individual with a variety of attributes, abil-
ities, problems, and experiences, and as a member of a group that is 
subject to family, social, and cultural inﬂ  uences; at different stages 
in the process of assessment each of these aspects will need separate 
consideration.
Analysis is needed to identify those attributes, experiences, and 
problems of the patient and the family that might require speciﬁ  c

problems of the patient and the family that might require speciﬁ  c 
interventions by different members of the team. This must then be 
followed by several types of synthesis (or bringing together of 
information) to enable attempts to understand both subjective and 
objective relationships between the patient and the illness. First, 
possible interventions must be placed in order of priority for 
action. Second, the whole programme needs to be reviewed at 
intervals so as to assess progress and decide about any additional 
interventions that are required. At these times of review, and 
particularly towards the end of the whole episode of illness, global 
statements about ‘overall improvement’ , or changes in ‘quality of 
life’ may be additional useful ways of summarizing and evaluating 
what has been happening from the viewpoint of the patient.
From complaints to formulation

Figure 1.8.1.1 demonstrates how the information contained in the 
complaints presented by the patient needs to be sorted out into dif-
ferent conceptual categories so that it can form the basis of actions 
by the various members of the multi-disciplinary team.
The top box represents the complaints. Unpleasant symptoms 
are likely to head the list, but inability to do everyday activities or a 
description of problems with relationships may well come ﬁ  rst. 
Symptoms that give a clue to disorders, diagnoses, and possible 
treatments may not be identiﬁ  ed without close questioning by 
someone who knows what to ask about.
The second box indicates that the complaints need to be sorted 
out into symptoms and impairments (an impairment in this sense 
is interference with a normal physiological or psychological func-

tion, as explained below). Some complaints are both symptoms 
and impairments: symptoms because it is known that they can 
contribute towards the recognition of an underlying diagnosis or 
towards the identiﬁ  cation of a disorder, and impairments because 
they indicate measurable interference with the function of a part of 
the body or of a particular organ. For instance, inability to remem-
ber the time of the day is a symptom (disorientation in time) 
that may contribute towards a diagnosis of some kind of dementia. 
It is also an impairment of cognitive functioning that is likely to 
interfere with the performance of everyday activities such as get-
ting up and going to bed at the correct time, and organizing house-
work.
The left-hand side of Fig. 1.8.1.1 represents the progress towards

work.
The left-hand side of Fig. 1.8.1.1 represents the progress towards 
the identiﬁ  cation of a disorder and perhaps even an underlying 
diagnosis. These are important concepts because they may indicate 
useful treatments and likely eventual outcomes. The right-hand side shows the progression from impairment of functions of parts 
of the body or organs, through interference with personal and daily 
activities to interference with participation in social activities.
A clinical assessment is not complete until all the components of 
both sides of Fig. 1.8.1.1 have been considered. In doing this, the 
different components and the two pathways of concepts will need 
to be given widely varying emphasis for different patients, and also 
for the same patient at different times. For instance, if there is a 
physical cause for a disturbance of behaviour, an accurate diagnosis

physical cause for a disturbance of behaviour, an accurate diagnosis 
of this will lead to the best possible chance of rapid and successful 
treatment. In contrast, if a disturbance of social behaviour has its 
origin in personal relationships or has been imposed upon the 
patient by the social prejudices of others, the correct diagnostic cat-
egory is unlikely to add much. An assessment of social networks 
and supportive relationships will be more relevant to deciding 
upon useful actions.
Life events and illness
For clarity, the right-hand side of Fig. 1.8.1.1 is given in a very com-
pressed form, but in practice it is likely to need dividing into sev-
eral components. The possibility of discovering relationships in 
time between life events and the onset of symptoms or interference 
with activities, particularly if repeated, should always be kept in

with activities, particularly if repeated, should always be kept in 
mind, since this may be relevant to management plans and the Fig. 1.8.1.1 Analysis and integration of information.

67
assessment of prognosis. The best guide to this will be a lifechart. 
The opinions of patients and families about the causes of illness must be listened to with respect, while bearing in mind that the attribution of illness to the effects of unpleasant experiences is a more or less universal human assumption that often has no logical justiﬁ  cation. Clinicians have to arrive at their own conclusions 
about such relationships by means of experience, common sense, and some acquaintance with research ﬁ  ndings. Researchers seeking 
robust evidence on this topic are faced with a very difﬁ  cult task, 
since the assessment of vulnerability to life events is a surprisingly complicated and controversial issue. The leading method in this ﬁ eld is the Life Events and Difﬁ  culties Schedule developed by

Brown and Harris; a bulky training manual has to be mastered during a special course, and this then serves as a guide to an inter-view which may last for several hours. The length and detail of these procedures illustrate well the technical and conceptual prob-lems that have to be faced.
(27–29)
Psychodynamics and the life story
‘Psychodynamics’ refers in a general sense to the interactions between discrete life events, personal relationships, and personality attributes, in addition to its use to cover internal psychological processes (such as defence mechanisms and coping strategies). All of these need to be examined when trying to understand which of several possible causes of an illness at a particular time is the most likely.
A mixture of knowledge about local social and cultural inﬂ  u-

ences and more technical psychological issues is needed for this appraisal of the patient’s life story, and suggestions about different components of the overall pattern may well come from different members of the team.
The internal psychodynamics of the patient often need to be 
considered in detail, and one way to do this would be to construct a 
subdivision of the right-hand side of Fig. 1.8.1.1 to show interper-
sonal relationships and psychodynamic processes. In some patients a major conclusion of the initial assessment will be that these aspects are paramount, indicating the need for referral to a special-ist psychotherapy service. The assessment of suitability for speciﬁ  c 
forms of psychotherapy and cognitive behavioural approaches are dealt with in section 6.
Contextual inﬂ  uences on assessment 
procedures
The place of assessment should not be regarded as automatically

The place of assessment should not be regarded as automatically 
ﬁ xed in the outpatient or other clinical premises. One or more 
assessment interviews at home should be considered,(30) since the 
patient and family may feel much more at ease and therefore likely to express themselves more freely in familiar surroundings, but with the proviso that privacy may be more difﬁ  cult to achieve. The 
assessor will often be surprised how much useful information about the home and family circumstances is gained from an inter-view at home, even when there appeared to be no special reason for this at ﬁ  rst. In addition, the behaviour of both the patient and fam-
ily members in the clinic or hospital is often different from that observed in familiar home surroundings. There are also obvious advantages to both assessment and care at home for mothers who have psychiatric disorders in the puerperium.
(31)

(31)
Interviews on primary care premises are also often appreciated 
by patients who dislike going to hospitals of any sort, and the ease of consultation with the general practitioner is an additional 
advantage. The adoption of regular visits by a consultant psychia-trist to primary care premises as a major element in cooperation between psychiatrists and general practitioners is a style of work that seems to be spreading, with advantages to all concerned.
(32)
Privacy of interviewing  and conﬁ  dentiality  of what is discussed

(32)
Privacy of interviewing  and conﬁ  dentiality  of what is discussed 
needs careful consideration; there are few absolute rules, but the following points of procedure should be explained clearly to both patient and relatives from the start. First, the patient and any mem-ber of the family should know that if they wish they are entitled to speak to the doctor in private, and they must be able to feel that what they say will not be conveyed to any other member of the family unless they request this. Second, in addition to the usual rules of professional secrecy, the patient must agree not to question other family members about what they said to the doctor, and vice versa. These may seem to be elementary points to trained profes-sionals, but they are often not appreciated by patients or relatives who may be in fear of each other, or at least apprehensive about the reaction of the other on learning that statements they might con-

strue as critical have been made about them. These are all points by 
which trust is established and maintained between patient and doctor, and for the same reason any attempts by relatives to seek interviews on condition that the occasion is kept secret from the patient should be ﬁ  rmly resisted.
An interpreter  should always be sought if the patient cannot 
speak ﬂ  uently in the language of the interviewer. Mental health 
professionals who can also act as interpreters are increasingly avail-able nowadays due to the presence of almost all communities of sizeable ethnic minorities. Because of the issues of conﬁ  dentiality 
noted above, a professional of the same sex as the patient should always be preferred to family members when interpretation is needed.
Language barriers are usually, but not always, accompanied by a

Language barriers are usually, but not always, accompanied by a 
cultural difference. The interviewer must remember that the concept of a private interview between two strangers in which personal and often unpleasant events and experiences are discussed freely comes from ‘middle-class western’ culture, and is not necessarily shared by persons from other cultures. A discussion of this point before the interview with a mental health professional familiar with the patient’s background will help the interviewer to determine what to aim at in terms of intimate or possibly distressing information.
Multiple sources of information are always an advantage for 
those topics (mainly events) for which objective accounts are possible. Clinical experience is the best guide as to which account to use when conﬂ  icts of information arise. Serious conﬂ  icts of

those topics (mainly events) for which objective accounts are possible. Clinical experience is the best guide as to which account to use when conﬂ  icts of information arise. Serious conﬂ  icts of 
information arising during the initial assessment that involve the 
patient’s account of events are best resolved by trying to obtain 
more information. Confrontation of the patient with important conﬂ  icts of information should be avoided since it easily leads to 
misunderstandings. If done at all, confrontation should be reserved for later stages in the overall management when it forms part of a planned intervention with a special purpose.
Assessment as a multi-disciplinary activity
Multi-disciplinary teams can take many forms, varying from the tightly organized and necessarily hierarchical surgical theatre team in which the role of each member is clearly deﬁ  ned and unchang-

ing, to loosely knit groups in other types of health service in which 1.8.1 the principles of clinical assessment in general psychiatry

SECTION 1  the subject matter of and approach to psychiatry 68
only some of those attending meetings about patients regard what 
is taking place as a team event. For the purposes of discussion of the types of multi-disciplinary teamwork increasingly to be found in the mental health services, it is useful to differentiate between multi-disciplinary practice, familiar to many generations of mental health workers, and the more recently evolved multi-disciplinary teamwork. Both of these styles of work have many variations, but they both have some key features that need to be recognized by those involved.
In multi-disciplinary practice  the consultant or most senior

In multi-disciplinary practice  the consultant or most senior 
doctor present at clinical meetings or ‘ward rounds’ is accepted by all as the leader of the group, and listens to (and usually depends upon) the views of the senior nurses and other health professionals who may or may not be present. But the decisions about treatment and management are clearly acknowledged to be the responsibility of the doctors present. In most settings the only essential attendees at these meetings are the doctors and nurses; attendance of other health professionals is usually welcomed and valued, but they are not regarded as necessary members of the group.
Multi-disciplinary teamwork  has probably developed in

Multi-disciplinary teamwork  has probably developed in 
response to a marked increase in the number of social workers, occupational therapists, clinical psychologists, and others, in those medical services in which patients and families with multiple needs are the rule rather than the exception. Clinical skills and techniques that were not previously available are now available, and the health professionals offering these expect quite naturally to be given increased personal and professional recognition; this can usually be found as a member of a multi-disciplinary team of the sort described here. The most fully developed style of multi-disciplinary teamwork involves a very signiﬁ  cant commitment of professional 
time by each member so that all the team meetings can be attended, in addition to the time spent directly with the patient and family.
Some sharing of responsibilities and blurring of roles is needed,

Some sharing of responsibilities and blurring of roles is needed, 
but each member also must be seen as retaining the professional skills of their parent discipline. Role blurring is most obvious in the information-gathering and information-sharing phases of assess-ment, and in the team discussions that lead to agreement about the content of a programme of activities.
Leadership
The concept of a team implies that a team leader is recognized, but a leader does not have to be an obviously dominant speaker and decision maker. Many successful team leaders ‘lead from behind’ to great effect and to everyone’s satisfaction. The main reasons for having an agreed leader are, ﬁ  rst, to keep discussions acceptably 
brief and to a practical timetable; second, to facilitate decisions between reasonable alternatives; and third, to arbitrate when insoluble disagreements arise between team members.
There are a number of settings within the mental health services

There are a number of settings within the mental health services 
in which there may be no need for the leader for everyday purposes to be a doctor. This occurs most frequently in special crisis intervention and emergency units, in rehabilitation units, and in services for those with mental retardation. However, members of such teams have to acknowledge that decisions about the presence 
of physical illness, and the need for medication or laboratory 
investigations, can only be made by a medically qualiﬁ  ed person. 
The team then has to accept the authority of the doctor on these occasions because of the unique ethical and legal responsibilities that accompany a medical qualiﬁ  cation.In teams running an inpatient unit such as an acute admission 
ward, there is a clear need for the whole team to accept that medical and nursing members have free a ccess to all the pat ients for purposes

ward, there is a clear need for the whole team to accept that medical and nursing members have free a ccess to all the pat ients for purposes 
of physical examination, laboratory investigations, the administra-tion of medication, and a variety of nursing procedures.
Key workers and the planning of care
The allocation of a team member as key worker (or case manager) for each patient being assessed is the usual method of work in teams of this sort. Which member becomes key worker for which patient depends upon the ability of the team to match the needs of each patient with the skills available amongst the team members, according to their training. Although all patients are discussed in detail at team meetings, and any team member can contribute suggestions and viewpoints, it is usually accepted that once a programme of activities is identiﬁ  ed and agreed upon, most if not

all of the contacts with the patient and family will be made by the key worker. The key worker also has the responsibility of reporting back to the team about progress, and about problems encountered which might require new major decisions or changes in the 
programme.
In the United Kingdom, due to yet another recent reorganization 
of primary care and hospital services, the situation with respect to urgent assessments and psychiatric emergencies has recently become complicated. Fundamental structural changes are taking place as a result of administrative and ﬁ  nancial pressures rather

than because of evidence from studies of the previous pattern of services. There is, however, now an element common to all areas in that the provision of a written plan for the care proposed is now a statutory responsibility for all patients. Further changes seem likely, and it is beyond the remit of the general principles of assess-ment described here to try to describe the present situation in the United Kingdom in detail. Reviews by Burns
(33) and others(34) are 
very helpful guides through the complexities and terms used to cover some of these developments in the United Kingdom.
In addition to the speciﬁ  c medical responsibilities noted above,

In addition to the speciﬁ  c medical responsibilities noted above, 
psychiatrists as members of a multi-disciplinary team have other important areas of expertise that should be recognized by the other members. Experienced psychiatrists are likely to have special skills in the assessment of dangerousness and risks of various sorts, and psychiatrists at any stage in their training should be able to show that they are specially trained to summarize information by the production of an overall formulation  that reflects the agreed 
policies of the team.
T o be an efﬁ  cient and accepted long-term member of a multi-
disciplinary team of this type requires personal characteristics not 
necessarily possessed by all mental health professionals. T olerance

necessarily possessed by all mental health professionals. T olerance 
of the different viewpoints of other team members is essential, in addition to the professional skills needed to carry-out the work required.
The frequency of team meetings is determined by the size and 
nature of the workload. Special meetings to discuss topics not directly related to the patients are also usually found to be neces-sary, so as to deal with issues such as team policies, recruitment and appointments, relationships with outside agencies (for instance about too few, too many, or inappropriate referrals), interpersonal problems between team members, and work-related stress in the team members. This last problem is particularly important in teams dealing with crisis intervention and psychiatric emergencies

69
because of the need to maintain a rapid turnover of patients and 
families who are seen over only a limited period of time.
A different type of problem that may need sensitive handling by 
the team leader and others in authority outside the team itself is the relationship between the team members and their immediate supe-riors (or ‘line managers’) in the hierarchy of their own discipline. Each team member has to strike a balance between personal needs for professional supervision and training, and the ability to make decisions within the team because of special skills not possessed by other team members. This type of problem will be minimized if team members are comparatively senior and experienced within their parent discipline. Student health workers are not appropriate as team members, but they can beneﬁ  t greatly if attached to the

team as observers. They will have the opportunity to learn some-thing about how other disciplines operate, which is an aspect of training usually absent from the rest of their training.
Disagreements often arise within a team about the best time 
for patients to be discharged from care, or about the precise time for referral when it is in the patient’s interests to be assessed by another service. In c ountries where outpatient services and inpatient

services are staffed by different teams under different organizations, there will be many such breaks in care, and multi-disciplinary teamwork can become frustrating. But where continuity of care between different parts of the general psychiatric services is the norm, the most frequent changes of care result from the need for the patient to be assessed for more specialized treatment such as rehabilitation, cognitive behavioural therapy, or intensive psy-chotherapy. The team needs to develop agreed policies for these occasions, and these will depend largely upon the structure of the local services available.
Although no systematic information is available, there is little

Although no systematic information is available, there is little 
doubt that the style of multi-disciplinary teamwork just described has become accepted in the mental health services in many coun-tries. Its popularity and success are probably due to the recognition of multiple rather than single needs in a large proportion of psychiatric patients and families, plus an increased job satisfaction experienced by the non-medical team members. Multi-disciplinary styles of working are especially important in emergency psychiatric services and crisis intervention units.
(35,36)
Instruments for assessment
Reasons for the development of structured 
interviewing and rating instruments
The training of all mental health professionals includes instruction

(35,36)
The training of all mental health professionals includes instruction 
in some system of information-gathering and recording based upon a conceptual structure that helps them to organize the large amount of information they usually need to collect. With training, the list of headings under which this information is collected becomes incorporated in the professional’s mind as an automati-cally available guide to the conduct of assessment interviews. For research purposes, however, it is necessary to demonstrate overtly that the essential topics have been covered in a comprehensive and systematic manner. In many types of research not only the head-ings covered but the detailed items also need to be recorded so that others studying the results of the research can be conﬁ  dent that

nothing was missed, and that the information obtained was not a biased selection of the total that might have been available. It has also been generally recognized since the 1950s that for purposes of communication between researchers in different centres, conclu-
sions must be based upon information that has been shown to have a satisfactory inter-rater reliability.
With these aims in mind, detailed and comprehensive structured 
interviewing and rating schedules for recording many varieties of information have been developed (nowadays these are usually called ‘instruments’; for brevity this term will be used to cover any sort of published interviewing and rating schedule). The most common types cover the present mental state and behaviour. Most of these instruments are not appropriate for use in everyday clinical work because they have been designed for research studies, but nevertheless it is useful for clinicians to know something about how they originated.
(37)

(37)
Since the ﬁ  rst appearance of partly or fully structured psychiatric 
rating instruments in the 1950s, there has been a steady increase in their number, type, and complexity. In the discussion that follows, some of the most widely used instruments are commented upon as examples but many others are available that are not mentioned. Comprehensive lists of such instruments can be found in catalogues of instruments and reviews by the WHO and others.
(38–42)
A word of warning is needed about the use of these instruments 
in ordinary clinical work. Any of them can be used as useful check-lists by clinicians to improve the range of information collected. But this does not mean that the quality of information recorded will necessarily be high. Most instruments were originally designed for use in research studies in which they were used by researchers specially trained in their use, and occasional use by untrained staff will not produce information of the same quality and usefulness.

Instruments for the assessment of mental state 
and behaviour
The instruments now available can be grouped according to the 
main purposes for which they were designed.
Screening instruments such as the General Health 
Questionnaire(43) are needed for the identiﬁ  cation of likely cases or 
high-risk individuals amongst large populations. These tend to be short and economical in use, since they have to be administered to large numbers of subjects. They are designed to generate a simple score that indicates the status of the subject in relation to the popu-lations upon which the instrument was developed and validated. This is essential for screening and for epidemiological studies, but this single score does not convey much about the details of the subject’s feelings or behaviour, and so is of limited interest to the clinician.
Screening instruments are often questionnaires, deﬁ  ning this to

Screening instruments are often questionnaires, deﬁ  ning this to 
mean that they are simply a means of recording the answers to a set of questions, without any further questions or enquiry about the extent to which the subject understands the question or wishes to 
qualify answers given. Questionnaires are usually ﬁ  lled in by the 
subject as a ‘paper-and-pencil’ exercise, as in the General Health Questionnaire, but one widely used questionnaire that has a very detailed content (the Composite International Diagnostic 
Interview
(44,45) ) is completed by an interviewer.
Detailed instruments may contain the following:
1 Symptoms of only one type, as in Hamilton’s rating scale for 
depression,(46) or the Scale for Assessment of Negative 
Symptoms.(47)1.8.1 the principles of clinical assessment in general psychiatry

SECTION 1  the subject matter of and approach to psychiatry 70
2 A selection of symptoms for the study of the relationships 
between two closely related types, such as depressive and schizo-phrenic symptoms in the Schedule for Affective Disorders and Schizophrenia.
(48)
3 A limited number of items covering different symptoms and 
behaviour selected as being of special importance, as in the recently developed Health of the Nation Scales of the United Kingdom.
(49)
4 A more or less comprehensive array of symptoms that allows 
the study of the relative distribution of symptoms of many different types, such as Schedules for Clinical Assessment in Neuropsychiatry
(50) and the Composite International Diagnostic 
Interview.(44,45) Other widely used but less tightly structured 
instruments with a comprehensive cont ent are the Brief Psychiatric 
Rating Scale(51) and the Comprehensive Psychopathological 
Rating Scale,(52) aimed at measuring change.

The source and method for collection of information is usually 
speciﬁ  ed by the designers of an instrument. These can include 
interviews with patients, relatives, and carers, observation of the patient, extracts from other documents, and any combination of these.
The more detailed instruments usually depend upon an inter-

view, and the style of interviewing recommended and the training needed to achieve this depend upon both the quality of the infor-mation required and the type of research interviewer for whom the instrument is designed. These vary widely; for instance, Schedules for Clinical Assessment in Neuropsychiatry require a clinical professional training plus a special course for the instrument itself; the Comprehensive Psychopathological Rating scale, the Brief Psychiatric Rating scale, and the Structured Clinical Interview for 
DSM
(53) assume a clinical professional training only. The Composite 
International Diagnostic Interview requires experience in inter-viewing such as market research plus a special course for the instru-ment itself, but no clinical professional training.

The time period covered varies from a cross-sectional picture of 
the present mental state and behaviour (‘present’ usually being taken to mean the immediately recent period of 2 or 4 weeks), to longer periods of follow-up, personal history, and development, and lifetime histories of psychiatric disorders. The more compli-cated and lengthy instruments that cover these longer periods are usually designed for particular studies, so are rarely suitable for general use.
Developments since the 1950s
A historical approach is helpful in trying to understand how and why the many instruments now available have developed. Hamilton’s Rating Scale for Depression, published in 1959, is a good example of the ﬁ  rst generation of instruments, most of which 
are comparatively short and simple.

(46) Its contents can easily be 
printed on one page, and comprise the following:
1 the names of the symptoms to be rated
2 a rating scale, the same for all the symptoms, by which the presence 
or absence and the severity of each symptom is recorded
3 a box in which the rating of each symptom is placed
No special recommendations about length and style of interview 
are given, and no explanations or deﬁ  nitions of the symptoms are given other than what is provided on the rating sheet itself. In other 
words, the interpretation of the ratings is based on the assumption that the raters have sufﬁ  cient experience and training to know what

words, the interpretation of the ratings is based on the assumption that the raters have sufﬁ  cient experience and training to know what 
most of their contemporaries also mean by the named symptoms. Data analysis is left to the user, other than recommendations about the likely meaning of the sum of the ratings with respect to severity of illness and ‘caseness’ . This and other early instruments were not tied to the use of any particular set of diagnostic categories, proba-bly because the diagnostic classiﬁ  cations that were available in the 
1950s and 1960s were not widely used.
The ﬁ  rst generation of instruments made it much easier for

The ﬁ  rst generation of instruments made it much easier for 
researchers to communicate the detailed results of their clinical studies to others, mainly by facilitating the study of changes in symptoms over comparatively short periods of time. The need for this was no doubt connected with the increasing numbers of psychotropic medicines that became available around that time. Measurement of change in symptoms is more immediately useful for the study of response to treatment than reliance upon statements about overall improvement or waiting for a change in diagnosis. But in the absence of guidance about how the symptoms are deﬁ  ned, problems still remain in the interpretation of the 
results.
Improvements in more recent instruments leading to better 
quality and meaning of the data they collect have been of two main 
types, in that the structure and the associated procedures of the

types, in that the structure and the associated procedures of the 
instruments have become more elaborate as time has passed. First, the input has been improved by the provision of written descrip-tions and deﬁ  nitions of symptoms, and by recommending particu-
lar styles of interviewing. This implies that researchers using the instrument should carry-out preliminary training work so that satisfactory levels of inter-rater reliability are achieved before starting the main study. Second, the output has been improved by the use of computers to organize and summarize the symptom ratings, allied with the development of widely used psychiatric classiﬁ  cations.
Computer programs based upon decision trees (algorithms) ﬁ  rst 
appeared in the 1970s, and are now commonplace. They allow the speciﬁ  cation of sets of symptoms that identify disorders or indicate

appeared in the 1970s, and are now commonplace. They allow the speciﬁ  cation of sets of symptoms that identify disorders or indicate 
diagnoses, so that the resulting statements about symptom proﬁ  les 
or the presence of disorders or diagnoses are free from errors of human judgement such as carelessness, simple forgetting, and personal variations from one occasion to the next. But the biases and assumptions built into the programs by their authors still remain, and these may be a problem to others with different opinions.
Programs can also be written to assign disorders and diagnoses 
according to a selected classiﬁ  cation, such as ICD-10 or DSM-IV , 
and some of the most recently developed instruments such as Schedules for Clinical Assessment in Neuropsychiatry and the 
Comprehensive International Diagnostic Interview are of this type.

Comprehensive International Diagnostic Interview are of this type. 
When used as intended, the data output from these more recent structured instruments is versatile and of high reliability, but to 
obtain these beneﬁ  ts the researcher has to pay the penalty of work-
ing hard to achieve and to maintain inter-rater reliability.
There are, of course, still plenty of uses for the simpler types of 
instruments; it is up to those designing and carrying out a study to decide what type of information they need and why, and to select their instruments accordingly. For the sake of those who will be interested in trying to interpret the results, a justiﬁ  cation of the

71
quality of the information obtained should always be included in 
the description of the ﬁ  ndings.
Once an instrument (or often a related group of instruments) 
has demonstrated its usefulness it is likely to stay in use for many years, while at the same time being subject to extensions and improvements. Families of instruments and traditions of inter-viewing style therefore develop and persist in the major research centres and groups, and it is possible to identify some of these and follow them over the years.
Three such traditions of instrument development are selected

Three such traditions of instrument development are selected 
for mention so as to illustrate the continuity and close relation-ships that sometimes exist between different instruments; these relationships may not be apparent from reports of studies in which they have been used. Three research centres that have produced particularly prominent sets of instruments are the Medical Research Council Social Psychiatry Unit at the Institute of Psychiatry in London, Biometrics Research at the New Y ork State Psychiatric Institute at Columbia University, New Y ork, and the Department of Psychiatry at Washington University, St Louis, Missouri. The instru-ments mentioned below are only a small proportion of the many in the literature, but they are well known because of their association with some large collaborative international research studies and with widely used classiﬁ  cations of psychiatric disorders such as 
ICD-8, ICD-9, and ICD-10, and DSM-III, DSM-IIIR, and DSM-IV .

At approximately the same time in the early 1960s, but indepen-
dently, research groups headed by John Wing, at the Institute of Psychiatry of the University of London (at the Maudsley Hospital), 
and by Robert Spitzer, at the Biometrics Research Unit at the New 
Y ork State Psychiatric Institute at Columbia University, began to produce structured interviewing and rating schedules that provid-ed extensive coverage of symptoms and were accompanied by recommendations for training procedures.
The present state examination
The present state examination ( PSE)(54) is a semi-structured pro-

cedure, based upon an interview schedule containing items that are rated as the interview proceeds. The content of the PSE has always been more or less comprehensive and it contains a number of symptoms, such as worry, muscular tension, restlessness, etc. that are not associated with particular diagnoses. These symptoms are included because they are often clinically obvious and also important to the patient (see comments below on ‘bottom-up’ and ‘top-down’ organization of interview schedules).
The ratings made by the interviewer do not depend entirely upon 
the immediate reply of the subject, but represent the interviewer’s clinical judgement as to whether or not the subject has the symp-toms as described in the glossary of deﬁ  nitions learned during the 
interview training. Questions are provided for all the symptoms and items and are used whenever possible in the order provided,

interview training. Questions are provided for all the symptoms and items and are used whenever possible in the order provided, 
but the order may be varied if the interviewer thinks ﬁ  t. The inter-
viewer is also encouraged to ask any other questions that seem relevant to determine the timing, frequency, and severity of the symptoms, as in an ordinary clinical interview. In other words, the interviewer aims to conduct a clinical interview that has been structured as much as possible so as to allow symptoms to be rated with high inter-rater reliability, but without seeming to be unpleas-antly rigid to either the subject or the interviewer. Much practice and training are required before these aims can be achieved, but there is no doubt that it is possible.The PSE was not developed with any particular diagnostic 
classiﬁ  cation in mind. It was intended from the start simply to be a 
means of arriving at a comprehensive and deﬁ  ned set of symptoms

means of arriving at a comprehensive and deﬁ  ned set of symptoms 
described in a reliable manner, with the user being left to decide whether and how to condense the symptoms into groups and what to do with the results. This is sometimes referred to as a ‘bottom-up’ style of instrument organization. Versions 7 and 8 of the PSE were ﬁ  rst used on a large scale in two studies that involved inter-
national collaboration and comparisons, namely the United States–United Kingdom Diagnostic Project between London and New Yo r k ,
(55,56) and the International Pilot Study of Schizophrenia 
coordinated by the WHO, Geneva.(57) Since then its content has 
been revised and extended as versions 9 and 10, but the techniques of interviewing and rating remain the same. PSE-10 is one of the main components of Schedules for Clinical Assessment in Neuropsychiatry.
Schedule for affective disorders and schizophrenia, and

Schedule for affective disorders and schizophrenia, and 
the structured clinical interview for DSM
The series of instruments developed by Spitzer and his colleagues 
at Biometrics of the New Y ork State Psychiatric Institute have been of several different kinds and, in the early years at least, had a much more rigid structure than the PSE. Users of the Mental Status Schedule and the longer Psychiatric Status Schedule were instruct-ed to follow the order of the questions as printed in the schedule, the only deviation from this being a repetition of the same questions if thought necessary by the interviewer. However, later instruments such as the Schedule for Affective Disorders and Schizophrenia
(48) and, more recently, the Structured Clinical 
Interview for DSM-III and DSM-IV(53) allow more ﬂ  exibility for

Interview for DSM-III and DSM-IV(53) allow more ﬂ  exibility for 
the interviewer in both interview style and the choice of a little or a lot of training (despite its length, the Structured Clinical Interview for DSM is recommended for clinical use as well as for research). There has also been an increasing tendency for instruments from the New Y ork group to be dedicated to a particular purpose. For instance, the content of the Schedule for Affective Disorders and Schizophrenia is keyed towards the study of relationships between schizophrenia and affective disorders, and the Structured Clinical Interview for DSM contains only those items that are necessary for identifying disorders present in the corresponding DSM. Like the Diagnostic Interview Schedule mentioned in the next section, the Schedule for Affective Disorders and Schizophrenia and the Structured Clinical Interview for DSM have a ‘top-down’ structure,

meaning that their content is determined from the start by an 
already existing set of criteria or symptoms.
The instruments produced by these two centres in the 1960s and 
1970s have been used widely in many countries, and their success led to the production of many similar instruments by other researchers. The adoption of the PSE for use by the WHO in a number of international collaborative studies also led to its being translated into more than 25 languages, with varying but never extensive degrees of adaptation to ﬁ  t the different cultures and 
social settings involved.
The diagnostic interview schedule
The third major research group is based at Washington University, St Louis, Missouri, and is well known as the originator of the ﬁ  rst 
widely used sets of Diagnostic Criteria for Research .
(58) Following 
the publication of DSM-III in 1980, there was considerable interest 1.8.1 the principles of clinical assessment in general psychiatry

SECTION 1  the subject matter of and approach to psychiatry 72
in discovering how the disorders it contained were distributed in 
the American population. Supported by the National Institute of Mental Health, Lee Robins and her colleagues designed the Diagnostic Interview Schedule ( DIS)
(59) for this purpose. This is 
composed of questions covering the symptoms required to identify 
what were considered to be the 15 most important disorders in DSM-III. The Epidemiological Catchment Area study of the National Institute of Mental Health, the very large study in which the DIS was ﬁ  rst used, included a population sample of more than 
18 000 subjects in ﬁ  ve largely urban areas.
(60)
So as to avoid the costs and other problems involved in employ-

(60)
ing trained psychiatrists or psychologists as interviewers, the DIS was designed as a highly structured questionnaire adminis-tered as an interview by lay interviewers. The interviewers, usually already experienced in interviewing for market research, had to undergo a week-long intensive training course on the DIS. The DIS questions must be given in the order printed in the schedule. Possible symptoms are not rated as present if in the opinion of the subject they may be due to physical disorders, but there is no free questioning about timing, severity, and other details of the symptoms. Questions may be repeated, but only questions provided in the schedule may be asked of the subject. This is a very different concept from that of the PSE technique, and it is based upon the assumption made by the designers of the DIS that by

controlling the interviewer in this way, the DIS would ‘enable the 
interviewer to obtain psychiatric diagnoses comparable to those a psychiatrist would obtain’ .
(60) Put in another way, this is an assump-
tion that expressed complaints can be used as near equivalents of inferred symptoms for the purposes of identifying psychiatric disorders.
Schedules of clinical assessment for neuropsychiatry 
and the composite international diagnostic interview
Although originating from different groups with different tradi-
tions and purposes, the PSE and the DIS have now given rise to direct descendants, namely the Schedules of Clinical Assessment for Neuropsychiatry ( SCAN ) and the Composite International 
Diagnostic Interview ( CIDI ), that are closely connected. During 
the early 1980s, a collaborative programme of work between WHO and the National Institute of Mental Health of the United States (known as the Joint Project) resulted in the transformation of DIS into CIDI

(61) by increasing its contents by adding large parts of ﬁ  rst 
DSM-IIIR and then of the drafts of ICD-10 and DSM-IV . This was matched by the evolution of PSE-9 into PSE-10, the centrepiece of SCAN,
(50) whose content similarly covers almost all of both 
ICD-10 and DSM-IV . The only sections of ICD-10 and DSM-IV not now covered by SCAN and CIDI are those dealing with disor-ders of adult personality, disorders of childhood and adolescence, and mental retardation.
The coordination by WHO of the development of the ﬁ  nal stages

The coordination by WHO of the development of the ﬁ  nal stages 
of SCAN and CIDI has been aimed at the production of two instru-ments with different but complementary uses in epidemiological studies. CIDI can be administered to comparatively large numbers of subjects in the community since the use of lay interviewers keeps costs to a minimum. SCAN is more suitable for the professional (and therefore more expensive) assessment of subjects with obvi-ous or severe disorders, whether these have been selected from a larger population by means of CIDI or other screening instru-ments, or whether they are being studied clinically for other reasons. The latest development in this long-term programme has 
been the establishment of WHO-sponsored training centres in a number of countries. Psychiatrists and other mental health profes-sionals can now obtain the necessary training for both SCAN and CIDI in English, French, German, Spanish, Chinese, Japanese, and Arabic.
(61)

(61)
These and other instruments will no doubt be developed further, 
but every new instrument and every change to an existing one carries with it problems of data interpretation. Even though the content of changed or new instruments may seem to be the same as their predecessors, quite small changes in the method or the sequence of questions may have important effects, particularly for highly structured instruments in which the ratings are not ﬁ  ltered 
through the clinical judgement of a trained mental health profes-sional. For instance, a recent report from the United States
(62)
discusses the possibility that the differences in prevalence rates for some disorders found between the Epidemiological Catchment Area study
(60) and the more recent Co-morbidity Study(63) are due 
at least in part to changes in the ‘stem questions’ that introduce other speciﬁ  c questions rather than being due to real differences in 
the community subjects.

There are also unsolved problems in the study of individuals in 
the community, who have not sought professional help, by means of instruments originally designed for the study of psychiatric patients already in contact with services. T o fulﬁ  l the criteria for 
a psychiatric disorder does not necessarily indicate a need for treatment, since the assessment of ‘caseness’ requires more than a simple count of symptoms. The debate about this problem has now stretched over 20 years, but needs to continue,
(64,65) together 
with further examination of the closely related topic of clinical validity.
(66)
Other selected issues
The importance of negative symptoms  in the assessment of indi-

(66)
viduals with schizophrenic syndromes has led to the development of instruments devoted to these symptoms; the Scale for the Assessment of Negative Symptoms
(47) is one of the most widely 
used, particularly in the United States. The Psychological Impairments Rating Scale (WHO/PIRS)
(67) has been found to be 
acceptable in a variety of cultural settings, and has been used in several large international collaborative studies coordinated by the WHO. Both these instruments and a variety of others are useful as checklists for ordinary clinical purposes.
(68) However, because of 
the nature of the symptoms being assessed, most of them are still beset with signiﬁ  cant problems about inter-rater reliability and the 
exact meaning of their constituent items.

The assessment of personality  poses special problems because 
to obtain a satisfactory account of a individual’s personality, how-ever the concept is deﬁ  ned, requires much more than the views of 
that individual; additional accounts of personal development and relationships from relatives or close friends are needed for comparison. Current concepts of personality disorders as listed in ICD-10 and DSM-IV also have serious limitations; the problems are well illustrated by a recent large international collaborative study coordinated by the WHO, using the International Personality Disorder Examination (IPDE).
(61) Several hours of skilled inter-

viewing are required, with at least two informants, to cover the content of the items that are needed to identify the disorders of adult personality contained in both the above classiﬁ  cations.

73
This study and others with similar aims have found that if an indi-
vidual fulﬁ  ls the criteria for one disorder of personality, they are 
quite likely to fulﬁ  l the criteria for at least one more. This implies 
that the present categories reﬂ  ect only parts of the overall personal-
ity; this may be quite useful, but a fairly drastic overhaul of the currently used categories is clearly needed.
Clinically, it is useful to assess three aspects of personality, 
according to the salience of personal characteristics and problems arising from them. First, one or more of the personality disorders described in ICD-10 or DSM-IV should be used only if there are quite clear accounts of repeated problems and behaviours as speciﬁ  ed, and they are not due to symptoms of any other disorders

that may be present. Second, for less severe but repeated problems and behaviours, the concept of ‘accentuated personality type’ is often useful, described simply by a short list of ordinary adjectives. These indicate recurring behaviours and attitudes likely to cause a variety of mild interpersonal or social problems, again not attributable to symptoms of other disorders. Finally, even though neither of these ﬁ  rst two types of personality disturbance is pres-
ent, it is always worthwhile describing the usual characteristics of the patient by means of a few adjectives (such as ‘a worrier’ , some-what shy and socially inhibited, deﬁ  nitely gregarious, etc.). Vaguely 
optimistic terms commonly offered by friends and relatives, such as ‘happy-go-lucky’ , should be avoided.
Multiaxial descriptive systems  (often optimistically called 
classiﬁ  cations) have been available for many years,
(69) and now

(69) and now 
apply to both ICD-10 and DSM-IV . Multiaxial systems describe several aspects of the person in addition to the disorder, and can be regarded as providing a systematized formulation that facilitates the coded recording of several aspects of the person concerned. Most of them have been designed more for research than for every-day clinical use, but they can all serve as very useful checklists when preparing for clinical reviews. DSM-IV , like DSM-III, is presented as a multiaxial scheme covering ﬁ  ve aspects of the subject (Axis I, 
clinical disorders; Axis II, personality disorders and mental retarda-tion; Axis III, General Medical Conditions; Axis IV , Psychosocial and Environmental Problems; Axis V , Global Assessment of Functioning). Similar instruments are now available for ICD-10,
(70)

(70)
covering general adult psychiatry and the psychiatry of childhood and adolescence (see Chapter 1.9 and 9.1.1).
Quality of life  has come to the fore in recent years, but in the 
same way as for multiaxial assessment, to use this term does no more than make explicit something that has always been implicit in a good clinical assessment. Examination of the content of the many assessment instruments that are now available with this title shows that they contain various mixtures of almost every possible attri-bute of the person, the illness, and the environment. There is no point in using a new term when the information collected refers only to already familiar problems such as symptoms, disablements, 
how the patient’s time is occupied, and contacts with medical 
services. There is even a considerable literature on the ‘quality of life’ of whole communities and countries, in which indices are 
calculated from national or regional statistics about, for instance,

calculated from national or regional statistics about, for instance, 
standards of housing, education, transport, and consumption of material resources. Such indices are of value to economists and demographers, but are far removed from clinical assessments. There is much to be said for using the term in clinical work only when it indicates ‘higher-level’ value-judgements and concepts such as personal satisfaction, self-fulﬁ  lment, and freedom from distress. Most of these are subjective and difﬁ  cult to measure, but 
in many ways they reﬂ  ect the ultimate aims of all medical care. 
An excellent recent review of this topic from the viewpoint of psychiatry is available,
(71) which illustrates well the wide range of 
subjects now covered by the term.
Service research into the closely related needs assessment  has

Service research into the closely related needs assessment  has 
resulted in the production of some detailed instruments that, again, are of interest to clinicians largely as potential checklists. A good example from the United Kingdom is the MRC Needs for Care Assessment.
(72)
Administrative pressure to provide some sort of quantiﬁ  cation 
of clinical outcome  has resulted in several comparatively brief 
instruments designed for clinical use. Two widely used examples are the Global Assessment of Functioning ( GAF ) scale (Axis V of 
DSM-IV) and, in the United Kingdom, the recently developed Health of the Nation Outcome Scale ( HONOS ).
(49)
In both of these, the assessor uses whatever information is avail-

(49)
able about the patient to make judgements about the presence and severity of symptoms and troublesome behaviour, and the extent to which these interfere with activities, relationships, and social performance. In the GAF scale this is expressed as a single overall score. In HONOS, 12 separate ratings are made which can be used independently, or added together to give an overall score if required. This type of instrument is likely to become increasingly important as the demand for ‘evidence-based medicine’ spreads, since they are designed for use by virtually any health professional in almost any setting. So long as precautions are always taken to ensure that the ratings made are as reliable and as valid as the setting permits, and likely sources of bias and error are kept in mind, their use can be a valuable aid to many forms of clinical assessment.
One further example of a comprehensive assessment instrument

should be mentioned because it was designed for both research and clinical purposes, and it has been at times widely used in a number of European countries. The ADMP (an acronym in both German and English for the Association of Methodology and Documentation in Psychiatry) exists in English, German, French, Spanish, and Japanese versions, covering virtually all the information needed for a comprehensive assessment by means of lists of items to be coded as present or absent. It is up to the user to decide the meaning of each item, and how much to train with fellow raters (or not) so as to improve inter-rater reliability.
(73)
The condensation and recording of 
information
Summary and formulation
The skills required to produce summaries and formulations should

The skills required to produce summaries and formulations should 
be acquired early on in professional training, since they are central to the process of getting the information about the patient into a form which facilitates the making of decisions and the allocation of priorities for actions. Useful preliminaries to the writing of both summary and formulation are the preparation of a problem list and a lifechart; how to prepare these should also be covered in the early stages of training. The summary for an individual patient should be more or less the same whoever prepares it, since it should be a simple record of what is known, arranged under conventional headings. A ‘telegram’ style of writing is acceptable for the sake of brevity. In contrast, a formulation should be written as a gram-matically correct narrative, and there is no necessary expectation 1.8.1 the principles of clinical assessment in general psychiatry

SECTION 1  the subject matter of and approach to psychiatry 74
that two different clinicians using the same summary about a 
patient would arrive at exactly the same conclusions in their for-mulations. This is because a formulation is an attempt by the writer to understand, and therefore to some extent to interpret, what has been inﬂ  uencing (and perhaps causing) the feelings and behaviour 
of the patient, and what relationships might exist between life events, illness, and contact with medical services.
Like the rest of the written medical records, the summary, 
formulation, and problem lists should be regarded as being as much for future readers as for the present carers. A clearly written summary and a well-argued formulation recorded in the case records will ensure that the reasons for treatments and decisions to do with the present illness are clear, and will be of great help to others if the patient has to be assessed in subsequent episodes of illness.

Summaries and formulations written by psychiatric members of 
a multi-disciplinary team should be freely available to all the team, so that they can be discussed before the meetings at which a diag-nosis is agreed and care programmes are set-up. But it is not usu-ally appropriate to send summaries and formulations made for hospital and team purposes to general practitioners or to consul-tants in other specialties. Specially written and shorter letters are best for this, taking into account the possibility that the patient or family may gain sight of, or even be shown, documents about them sent to other medical professionals.
Differential, main, subsidiary, and alternative 
diagnoses
A differential diagnosis should be placed in the case records in

diagnoses
A differential diagnosis should be placed in the case records in 
a prominent place, with a clear indication of who made it (‘diagnosis’ will be used in this section because of current conven-tions, but the difference between identifying a disorder and infer-ring an underlying diagnosis already noted must be kept in mind). When the patient suffers from more than one disorder it is usually possible to select one as the main diagnosis and specify the other(s) as additional or subsidiary diagnoses. The main diagnosis will usu-ally be the one that is leading to immediate action, but the choice may depend upon the purposes for which the diagnoses are being recorded. Usually it reﬂ  ects the reason for the current contact with 
services or admission but there are patients and occasions when, for instance, it makes more sense to record a lifetime diagnosis (such as schizophrenia or bipolar disorder) as the main diagnosis,

services or admission but there are patients and occasions when, for instance, it makes more sense to record a lifetime diagnosis (such as schizophrenia or bipolar disorder) as the main diagnosis, 
even though something else such as anxiety or a phobic disorder is 
the reason for the current episode of care.
When one main diagnosis clearly applies yet does not account 
for some symptoms which, although a signiﬁ  cant part of the 
clinical picture, still fall short of fulﬁ  lling the criteria for another

clinical picture, still fall short of fulﬁ  lling the criteria for another 
disorder, it is useful to record these simply as ‘additional symptoms’ (for instance, depressive disorder with some obsessional symptoms; agoraphobia with some depressive symptoms, etc.). Neither ICD-10 nor DSM-IV mention this way of recording symptoms ‘leftover’ after the main disorder has been accounted for, even though it is a useful clinical custom familiar to many generations of clinicians in a variety of countries. However, omission from formal classiﬁ  cations should not be allowed to inhibit clinicians from 
following clinical habits they ﬁ  nd useful.
When there is reasonable debate about what is the best diagnosis

When there is reasonable debate about what is the best diagnosis 
out of two or more possibilities, one must be chosen provisionally as the main diagnosis as a basis for action but the other should be recorded as an alternative diagnosis. It is also good practice in quite 
early stages of the assessment process to record provisional diagno-ses, which can then be changed as more information becomes available. About a third of psychiatric patients fulﬁ  l the criteria for 
more than one disorder as deﬁ  ned in current classiﬁ  cations, but as 
already noted, this does not carry the same implications about underlying morbid physiological, psychological, or anatomical processes as would a statement about the presence of the same number of medical or surgical diagnoses.
Making a prognosis
The ﬁ  nal statement in the formulation should be the prognosis.

The ﬁ  nal statement in the formulation should be the prognosis. 
This attempt to predict what will happen to the patient in the future should be expressed as clear statements about likely outcomes, avoiding vague comments such as ‘the prognosis is guarded’ (found all too often in case records). The patient and family usually hope to be told about the prospects for recovery and the likelihood of relapse. Efforts should be made to do this, but with due care to emphasize that a prognosis is only an estimate that may be proved wrong by events. A prognostic statement should contain predictions of such things as:
1 immediate response to treatment, assuming compliance2 duration of this episode of illness and/or stay in hospital3 degree of recovery from this illness (i.e. partial or complete) in 
terms of both symptoms and return to previous activities
4 risk of recurrence, stated as the likely position at speciﬁ  c points

4 risk of recurrence, stated as the likely position at speciﬁ  c points 
in time, depending upon the circumstances of the case (6 months, 
1 year, and 2 years from the present are often appropriate)
However difﬁ  cult it may seem, attempts should be made to 
record a prognosis in these terms, and to sign it. T o do this will fulﬁ l the legitimate expectations of the patient and family, and the 
clinician will make possible a uniquely valuable learning experi-ence when faced in the future with such statements about those patients seen in further episodes of care.
Reviews

Reviews
The initial assessment should produce a list of agreed actions to be carried out in a stated order of priority by the various members of the team. Division into immediate and medium-term actions will help the whole process, and also indicate the timescale of reviews to assess progress. One of the main functions of the acknowledged team leader is to keep an eye on the progress of all the patients in the care of the team, discussing with each key worker both outside and within team meetings the best timing of the next review. Review meetings should be recorded as such in the case documents, with conclusions about progress made and any changes in plans or objectives. It is particularly important, again for future readers of the records, to write down clearly whether there was any response treatment (it is very frustrating to read in a case record of treat-ments given in the past, and then to ﬁ  nd no indication of the 
result.)
Writing reports

result.)
Consultant psychiatrists are often asked by external agencies to provide written reports on patients for whom they have a current

75
clinical responsibility, and requests may also be received for a report 
on a patient they have not seen previously. The purpose of these external reports is usually different to that of the usual clinical communications undertaken in the ordinary clinical care of the patient, in that the request is usually for an opinion about one speciﬁ  c issue. These requests frequently involve an opinion on the 
risk posed to others by the patient’s inability to perform certain skills, or by the positive adverse effect of the patient’s problems on others. An opinion on the capacity of the patient to understand and competently agree about important issues is also frequently requested.
The purposes of reports
Reports requested by individuals or agencies (both judicial and non-judicial) will usually fall into one of four broad groups:
1 Protection of the public or an institution:
(a) life assurance and mortgage companies who are interested in

(a) life assurance and mortgage companies who are interested in 
the risk of suicide, or loss of earnings due to future illnesses;
(b) lice nsing authorities and transport companies who are 
concerned with ﬁ  tness to drive or risks due to the public, 
due to impairment of skills and judgement consequent upon psychiatric illness;
(c) employment and beneﬁ  t agencies who are concerned with 
ﬁ tness to work;
(d) e mployers or occupational health physicians who are 
concerned about the risk posed by the patient’s psychiatric disorder to an institution’s clients, or about the likelihood of periods of absence because of sick leave.
2 Protection of the patient:
(a) solicitors or courts may require reports on the competence 
of individual patients to conduct their ﬁ  nancial affairs, to 
protect themselves from exploitation, and to engage in civil contracts;
(b) bodies concerned with the Mental Health Act (in the United

(b) bodies concerned with the Mental Health Act (in the United 
Kingdom the Mental Health Act Commission and Mental Health Review Tribunals) may require reports on the com-petence of individuals to give informed consent to non-voluntary psychiatric treatment or inpatient care, and the risk to the safety and well-being of the individual patient posed by such treatment.
3 Child protection:
(a) Social Services Child Care Departments and others involved 
in the welfare of children may request reports of the super-vising psychiatrist for Child Protection Case Conferences on the contribution of a psychiatric disorder to the childcare problem, and on the likely impact of the psychiatric disorder on the future parenting of the patient;
(b) solicitors acting for all parties in childcare proceedings (the

(b) solicitors acting for all parties in childcare proceedings (the 
child, the Social Services Department, and the patient) may ask for a psychiatric report on a mentally ill parent about the likely risk to the child of suffering signiﬁ  cant physical, devel-
opmental, or emotional harm from the patient in question.
4 Medico-legal and compensation proceedings: lawyers acting for 
either the patient or an agency being sued may ask for a report on the impact of the event on the mental health of the patient, 
together with the nature of the psychiatric disorder and its prog-nosis. Such reports may be requested of the supervising consul-
tant, or of another psychiatrist as an independent expert.
Reports for forensic or criminal proceedings are dealt with in 
Chapter 11.15.
Guiding principles

The general principles noted below apply to all reports, whether the psychiatrist knows the patient because of current or previous clinical responsibility, or whether the report is on a patient whom the psychiatrist has not seen before (this latter is known as pro-viding an ‘expert opinion’).
(a) Conﬁ  dentiality
In most situations written consent must be obtained from the

In most situations written consent must be obtained from the 
patient before personal information can be given to an outside agency. In almost all situations involving the writing of a report on an individual to an outside agency, that individual will gain sight of the report or will be entitled to do so. It is therefore good clinical practice for the patient to be aware of the content of the report, and particularly of any opinions or recommendations it may contain. Nevertheless, there are certain situations where the duty of care to the public or to a child overrides the duty of conﬁ  dentiality, and 
in such circumstances the psychiatrist may write the report even without the patient’s consent.
(b) Partiality
The opinion of the psychiatrist is being sought as an expert profes-sional. The report should not be biased in favour of one side or another and should not be inﬂ  uenced unduly by the interests of the

commissioning agency or the psychiatrist’s view of the best inter-ests of their patient. This may cause difﬁ  culties if the patient is in 
the personal care of the psychiatrist because in most clinical situa-
tions psychiatrists try to be non-critical, non-judgemental, and supportive, tending to encourage rather than to prevent. But the 
best interests of the patient will not be served by being put in a situ-ation where the likely outcomes are failure to do what is expected or to function at a suboptimal level.
Structure of reports

All reports should have three main sections. First, the report should begin with the patient’s personal details and the reasons for which the report has been requested, together with the identity of the commissioning agency. It should also specify the relationship between the writer and the patient. If the patient is or was in the clinical care of the writer the duration of the care should be noted, and the date of the last occasion the patient was seen should be given. If a special interview had to be arranged with a patient not previously known, the duration and date of the interview should be stated. The sources of information other than the patient used to prepare the report should then be detailed, plus any other documents that have been read. Reports for civil, judicial, and child protection proceedings will also require a short paragraph on the current employment and status of the author of the report, and a note of any special experience of relevance.

The second section should describe in appropriate detail the 
patient’s personal, social, medical, and psychiatric history, the mental 1.8.1 the principles of clinical assessment in general psychiatry

SECTION 1  the subject matter of and approach to psychiatry 76
state and behaviour at examination, the diagnosis and differential

state and behaviour at examination, the diagnosis and differential 
diagnosis, and comments upon aetiology, management, and progno-sis. In almost all reports, the prognosis is the primary concern, so this should be given special attention. It is important to remember that one of the most reliable predictors of the recurrence of behaviours or episodes of illness in the future is the frequency of their occurrence in the past. Similarly, the vulnerability of the patient in the past (that is, any enduring predisposing factors and patterns of past precipi-tants) will tend to predict future vulnerability and the likelihood of further episodes of illness. Some mention of the past will therefore always be necessary, but in many instances this can be brief and reduced to a commentary of a few lines. But in other situations, par-ticularly those involving civil court actions or childcare proceedings, a more detailed account of the past will be necessary.

Certain aspects of the patient’s past history and previous levels 
of functioning will need to be highlighted depending upon the purposes of the report and the nature of the questions asked of the psychiatrist. For example, if the report has been requested by an occupational physician about the ﬁ  tness of a patient to return to

work, then attention will need to be paid in the report to the dura-tion of illnesses in the past and the amount of sick leave that has been taken. Detail will need to be given about the impact, if any, that the patient’s ill health has had on the past to his or her capacity to work. If the report has been requested in relation to the safety of the patient to care for a child, then information will need to be given in the past history of the patient about the previous impact of the patient’s illness on his or her capacity to care for children or any risks that the patient posed to a child in the past. Life assurance and mortgage companies are likely to be particularly interested in suicidal behaviour.
The last section should contain the opinion of the psychiatrist 
about the speciﬁ  c questions posed by the commissioning agent.

about the speciﬁ  c questions posed by the commissioning agent. 
These questions may be unrealistically simple or there may be requests for categorical assertions of outcome that are simply not possible. The writer must avoid falling into the trap of complying with unreasonable requests about certainties. One way of avoiding this is to give opinions about risks or outcomes by stating criteria that would indicate different outcomes with different likelihoods, expressed by words such as possible, probable, and deﬁ  nite.
In situations where one of the variables involved in the patient’s

In situations where one of the variables involved in the patient’s 
prognosis is the response of helping agencies and the availability of resources, great care must be exercised on the part of the report writer to ensure that this contingency is made clear. If possible, suggestions should be made as to how the availability of the required resources can be assured. When considering the likely impact of a future breakdown in the mental health of a patient on some other person, such as a child, consideration should be given not only to the direct impact of the illness but also to the indirect consequences and the presence or absence of other protective factors. For example, if a woman with schizophrenia lives with her parents who can safely take over the care of her child, then the impact of a further episode on that child may be much less than if 
she is living alone and the child needs to be removed into the care 
of the local authority.

An opinion is often requested on whether an accident or an 
act of omission such as medical negligence caused the current psychiatric disorder or disabilities of the patient. If the psychiatrist concludes that the accident or omission was deﬁ  nitely a contribut-
ing cause but not in itself sufﬁ  cient to cause all aspects of the existingdisorder and disability, then further comments will be expected on 
other possible contributing influences, such as predisposing personal traits, or special vulnerability to current adversities. In such circumstances, there should be an attempt to weigh the contributing factors in order of their aetiological importance.
The last section of the report is usually the best place to list

The last section of the report is usually the best place to list 
the sources of information used for the report, making clear distinctions between personal observations and information obtained by the writer, opinions and observations made by other team members, and written information obtained from other documents. There should always be a clear distinction between opinions based upon objective information and direct examina-tion, and suppositions based upon interpretations, speculation, and past clinical experience. If opinions based upon research conducted by others are given, then the sources of this information should be acknowledged and referenced in the usual manner.
The language of the report should be appropriate to the commis-
sioning agency. If the report has been requested by an occupational physician or medical ofﬁ  cer working for a company, then it is

sioning agency. If the report has been requested by an occupational physician or medical ofﬁ  cer working for a company, then it is 
appropriate to use accepted medical and psychiatric terminology. If the report has been requested by a civil or judicial authority, non-technical language should be used wherever possible and any medical or psychiatric terms used should be deﬁ  ned. At all times 
when writing psychiatric reports it is important to use psychiatric terms in an appropriate fashion according to a stated international classiﬁ  cation, and to avoid idiosyncrasies.
Moller, H.J., Engel, R.R., and Helmsley, D.R. (2001). Standardised 
measurement instruments in psychiatry. In Contemporary psychiatry. 
Foundations of psychiatry , Vol. 1 (eds. H. Henn, N. Sartorius, 
H. Helmchen, and H. Lauter), pp. 113–35. Springer-Verlag, Berlin.
Grounds, A. (1993). Psychiatric reports for legal purposes in

Grounds, A. (1993). Psychiatric reports for legal purposes in 
forensic psychiatry. In Clinical, legal and ethical issues  (eds. J. Gunn and 
P .J. Taylor), Chap. 22, p. 826–55. Butterworth—Heineman Ltd, Oxford.
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Handbook of psychiatry , Vol. 1 (eds. M. Shepherd and O.L. Zangwill), 
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1.8.2 Assessment of personality
The assessment of personality provides the context needed to

The assessment of personality provides the context needed to 
understand someone as a whole person with particular goals and values that they pursue with a unique emotional style. A person’s way of adapting to life experience can tell an experienced clinician much about his level of well-being and his vulnerability to various forms of psychopathology. Knowing a person’s personality well can allow a psychiatrist to predict what other mental and physical disorders are likely to occur in the same person or in the same fam-
ily. For example, individuals with antisocial personality are more 
likely to have substance abuse and less likely to have Parkinson’s disease than others.
(1) On the other hand, if you learn someone has 
substance abuse, then you can reasonably suspect that they may be

substance abuse, then you can reasonably suspect that they may be 
impulsive or novelty seeking. Recognition of the many associations between personality and psychopathology can greatly enhance clinical assessment and differential diagnosis in general.
Assessment of personality also helps to establish a therapeutic

Assessment of personality also helps to establish a therapeutic 
alliance and mutual respect, because it involves the sharing of unique personal and social information that distinguishes one person’s style of life from others. Patients feel understood and appreciated when their psychiatrist understands their motivation and can predict their reactions to different situations and people. On the other hand, no one likes to be reduced to a ‘case’ or a ‘label’ . Everyone is unique, and yet it is possible to explore the mystery of each person’s uniqueness in a systematic way. Consequently, effec-tive clinical assessment of personality is designed to understand a person’s emotions, goals and values, strengths and weaknesses in 
the context of the narrative of his life.
Understanding personality also helps in treatment planning

Understanding personality also helps in treatment planning 
because people differ markedly in the types of treatments to which they respond and with which they will comply. For example, personality traits predict much of the variability in response to antidepressants, whereas the symptoms of depression or other psychopathology do not.
(2,3)
Fortunately, personality can be well assessed clinically without 
psychometric testing in ways that are simple and brief as part of routine history taking and mental status examination. The clinical assessment of personality requires little extra time if the clinician is alert to non-verbal cues in a person’s general appearance, expres-sions, and behavior, as well as to the signiﬁ  cance of what is said and 
how it is said. Only brief questions to clarify complaints and their context may be needed.
Personality develops over time in response to a changing internal

Personality develops over time in response to a changing internal 
and external environment. As a result, the longitudinal course of a person’s development of personality and psychopathology is a key element in the clinical assessment of personality. Speciﬁ  cally, it is 
highly informative to know what a patient’s personality was like as a child when assessing him in the presence of additional psycho-
pathology, like a depression or anxiety state that modiﬁ  es his 
emotions, thoughts, and behaviour. However, personality traits are not ﬁ  xed and completely stable. Rather, each of us has a range of

emotions, thoughts, and behaviour. However, personality traits are not ﬁ  xed and completely stable. Rather, each of us has a range of 
thoughts, feelings, and behaviours at any given point in time. As a result, our personality traits frequently vary within that range and occasionally change by moving beyond the previous range in response to particular internal and external events. Understanding the course of a person’s development during his life is what allows the psychiatrist to understand him as a unique person.
In this chapter, I will try to explain the basic constructs and 
methods of personality assessment, so that a clinician can apply this knowledge in a ﬂ  exible and practical manner. If you have to ask 
standardized questions that are not tailored to opportunities that arise in the course of an interview, then you don’t understand the basic constructs adequately. On the other hand, some clinical features about personality traits are sufﬁ  ciently high in yield and

diagnostic value, that they should be assessed in a ﬁ  nal review 
if they haven’t been come up more spontaneously during the interview.

79
What is personality?
In order to assess something it is crucial to have a good understanding
of what it is and what it is not. People differ markedly from one another in their outlook on life, in the way they interpret their experiences, and in their emotional and behavioral responses to those experiences. These differences in outlook, thoughts, emo-tions, and are what actions characterize an individual’s personality. More generally, personality can be deﬁ  ned as the dynamic organi-
zation within the individual of the psychobiological systems that modulate his or her unique adaptations to a changing internal and external environment.
(4) Each part of this deﬁ  nition is important 
for a clinician to appreciate. Personality is ‘dynamic’ , meaning, it is constantly changing and adapting in response to experience, rather than being a set of ﬁ  xed traits. Inﬂ  exibility of personality is actually

an indicator of personality disorder. Personality is regulated by ‘psychobiological’ systems, meaning, personality is inﬂ  uenced by 
both biological and psychological variables. Consequently, treat-ment of personality disorders requires growth in psychological self-understanding and not just treatment with medications, although these can be helpful adjuncts to therapy.
(5,6) These sys-
tems involve interactions among many internal processes, so that each person’s pattern of adjustment is ‘unique’ to them, even though they follow general rules and principles of development as complex adaptive systems.
(7) Finally, to understand personality

(7) Finally, to understand personality 
and its development, we must pay attention to both the ‘internal’ and ‘external’ processes by which an individual interacts with and adapts to his own internal milieu and external situation. For exam-ple, when a person is under stress, he is likely to think and feel differently about himself and other people. On the other hand, when he is calm and encouraged, he may act more maturely and happily. Everyone has personal sensitivities or ‘rough spots’ that surface when they are under stress. Everyone has ‘good days’ and ‘bad days’ , and this pattern of variability over time is what charac-terizes a person’s unique personality conﬁ  guration.
An individual’s personality can only be adequately characterized 
in terms of interactions among different internal and external forces that inﬂ  uence a person’s emotions, thoughts, and behaviour.

in terms of interactions among different internal and external forces that inﬂ  uence a person’s emotions, thoughts, and behaviour. 
A person may feel and act differently on a date, at work, with trusted friends, at school, or in church. His personality doesn’t change, rather his personality can only be adequately assessed when the psychosocial context is speciﬁ  ed. Some traits are strong and perva-
sive regardless of the situation, but other aspects of personality may be markedly affected by the situation. Furthermore, the internal processes may modify a person’s outlook, as when his outlook is inﬂ uenced by prior or anticipated events, or when his goals and

values allow him to change his outlook in ways that are not predict-able by what he has previously done. Human beings have an amaz-ing ability to change their outlook for the better or the worse in ways that are unpredicted by their past or present circumstances. Personality traits can be described in ways that are moderately stable over time and situations, but a prudent clinician must never mistake average probabilities with predictive certainty.
Five major types of situations are useful to distinguish for human 
beings: Sexual situations involving reproduction and sexuality; Material situations involving the quest for material possessions and power; Emotional situations involving emotions and social attach-ments; Intellectual situations involving communication and cul-ture; Spiritual situations involving the quest for what is beyond individual human existence. The average person is concerned with material situations most of the time—obtaining food, clothing,

shelter, transportation, and striving for power and wealth. However, to understand a person fully it is essential to recognize his feelings, thoughts, and intuitions in other types of situations ranging from the sexual to the spiritual. The way a person adapts to these ﬁ  ve 
different types of situations correspond to layers of an individual’s personality. The treatment of psychopathology can be viewed as a working-through of problems and blind spots in these ﬁ  ve layers of 
everyone’s personality, enabling the development of self-awareness in the full range of life situations.
(8)
Personality involves much more than the description of a ﬁ  xed 
set of traits that allow the prediction of a person’s behavior. Personality involves the interaction of internal and external forces that inﬂ  uence the development of a person’s behavior, but

set of traits that allow the prediction of a person’s behavior. Personality involves the interaction of internal and external forces that inﬂ  uence the development of a person’s behavior, but 
nevertheless allow for the potential of a person to grow in self-awareness and thereby change in ways that cannot be predicted from his past behavior.
(9)
How can personality be described quantitatively?
Personality refers to the motivational systems within  a person, not

(9)
Personality refers to the motivational systems within  a person, not 
between individuals. In other words, to understand what motivates a person we need to recognize empathically what he is thinking and feeling within his own being. We need a model of the dynamic psychobiological processes within a human being. Unfortunately, the people who have developed most personality tests often treat each person as a black box that emits self-reports. As a result, most personality psychologists have failed to understand the internal dynamics underlying the thoughts and feelings of the people they assess. However, it is possible to describe a person’s internal pro-cesses, which interact with his or her external situations. In order to account for both the internal and the external inﬂ  uences on per-
sonality, it is essential to distinguish the dimensions of a person’s temperament and those of his character.
(4)

(4)
The temperament traits are biases in emotional responses that 
are fully developed early in life and relatively stable thereafter. On the other hand, character involves higher cognitive processes that develop in a stepwise manner over the life course to enable a person to regulate his emotions, achieve certain goals, and maintain par-ticular values and virtues. Initially, it was thought that character was less heritable than temperament, but empirical studies have shown that both are moderately heritable. The key difference is the difference in the pattern of learning and memory: the proce-dural learning of habits and skills inﬂ  uences the conditioning of 
temperament, whereas propositional learning of goals and values inﬂ uences the development of character. Both procedural and

temperament, whereas propositional learning of goals and values inﬂ uences the development of character. Both procedural and 
propositional learning interact with one another in self-aware consciousness so that a person can maintain a personal sense of 
continuity throughout many episodes of experience as the story of 
his life unfolds.
T emperament can be assessed in terms of four quantiﬁ  able 
dimensions, as measured by the T emperament and Character Inventory.
(4) These are described in Table 1.8.2.1, which shows that

(4) These are described in Table 1.8.2.1, which shows that 
each trait is manifested in slightly different ways depending on the situation. A situation necessarily depends on both the person’s out-look and the external circumstances themselves. For example, a person is described as high in Harm Avoidance if he is easily fatigued, fearful, shy, pessimistic, and inhibited. On the other hand, a person is described as low in Harm Avoidance if he is vigorous, risk-taking, beguiling, optimistic, and uninhibited.1.8.2 assessment of personality

SECTION 1  the subject matter of and approach to psychiatry 80
However, the level of Harm Avoidance varies moderately between 
situations. For example, some people who are shy are not easily fatigued, and some people who are shy meeting strangers are risk-takers when driving an automobile. The components of Harm Avoidance that are manifested in different situations are moder-ately correlated, and so it is useful to consider all these as part of a higher order trait that is moderately heritable and moderately stable across time and situations. Likewise, Novelty Seeking, Reward Dependence, Persistence are also moderately heritable and stable dimensions of temperament.
Likewise, there are three dimensions of character, which quantify

Likewise, there are three dimensions of character, which quantify 
the nature of a person’s goals and values (Table 1.8.2.2). Each of these character traits is comprised of components that are expressed in different situations. The character dimensions also correspond to key functions of a person’s mental self-government. As a result, character traits provide a rich description of key features of the mental status examination, including insight and judgment.
Insight refers to the depth of a person’s ability to recognize and 
understand the inner nature of things, rather than basing opinions 
on superﬁ  cial appearances. Insight is quantiﬁ  able as the character 
trait of Self-transcendence. A person with deep insight is respectful, mindful, and holistic in perspective, whereas one with little insight 
is unrealistic, shallow, and fragmented in perspective.
Judgment refers to a person’s legislative ability to cooperate

Judgment refers to a person’s legislative ability to cooperate 
and get along with others in ways that are appropriate and ﬂ  exible, 
and can be quantiﬁ  ed as the character trait of Cooperativeness. 
A person with good judgment is cooperative and principled, whereas a person who has poor judgment is uncooperative and opportunistic.
Foresight refers to a person’s executive ability to anticipate what 
will be satisfying in the long-term or in the future. This executive 
function allows a person to follow a life path that maintains

function allows a person to follow a life path that maintains 
well-being. A person who is far-sighted is responsible, purposeful, resilient, and resourceful, whereas one who learns from hindsight only is irresponsible, aimless, fragile, and inadequate. In addition, foresight leads to cheerfulness and spontaneity, whereas reliance on hindsight is associated with moodiness and conventionality. Accordingly, the degree of a person’s foresight provides important clinical information about a person’s ability to appreciate what is real, meaningful, and satisfying. As a result, a person’s self-directedness is an important indicator of reality testing, maturity, and vulnerability to mood disturbance. Self-directedness is high Table 1.8.2.1  Descriptions of temperaments according to emotional responses elicited by particular external situations and internal outlooks

Temperament Sexual situations Material situations Emotional situations Intellectual situations Spiritual situations
Harm Avoidance Fatigable
vs
VigorousFearful
vs
Risk-takingShy
vs
BeguilingPessimistic
vs
OptimisticInhibited
vs
Uninhibited
Novelty Seeking Craving
vs
ReservedExtravagant
vs
FrugalIrritable
vs
StoicalImpulsive
vs
RigidExploratory
vs
Immobile
Reward Dependence Insecure
vsIndependentSympathetic
vsAloofSociable
vs
DistantSentimental
vsIndifferentAttached
vs
Detached
Persistence Ambitious
vsApatheticOverachieving
vsUnderachievingLoyal
vsFickleDetermined
vsAmbivalentPerfectionistic
vsPragmatic
Table 1.8.2.2  Descriptions of the three dimensions of character according to the ﬁ  ve layers of everyone’s personality, which are deﬁ  ned by  the 
predominant focus of the person’s internal perspective on the external situation. Within each layer of personality, maturation and integration

predominant focus of the person’s internal perspective on the external situation. Within each layer of personality, maturation and integration 
involves increasing each of the three character dimensions, which describe the functions of insight, judgment, and foresight. I ntegration of the 
whole person requires working through these functions in each of the layers of personality
Cognitive function 
(Character dimension)Characteristics of the 
sexual layerCharacteristics of the 
material layerCharacteristics of the 
emotional layerCharacteristics of the 
intellectual layerCharacteristics of the 
spiritual layer
Insight (Self-Transcendence)Trustful
vs
Alienated
(prelogical categorizing)Free-Flowing
vs
Compulsive
(concrete-vivid logic)Identifying
vs
Avoiding
(emotive imagery)Creative
vs
Imitative
(abstract symbols)Intuitive
vs
Conventional
(preverbal  schemas)
Judgment
(Cooperativeness)Tolerant
vs PrejudicedForgiving
vs
RevengefulEmpathic
vs
InconsiderateHelpful
vs
UnhelpfulPrincipled
vs

vs
Judgment
vs
vs
vs
vs
Opportunistic
Foresight
(Self-Directedness)Responsible
vsIrresponsiblePurposeful
vs AimlessResilient
vs MoodyResourceful
vs InadequateSpontaneous
vsPredetermined

81
in people who are mature and happy, whereas it is low in people 
with personality disorders and in those vulnerable to psychoses and mood disorders.
Psychometric testing of personality traits
A wide variety of psychometric tests can be used to describe per-sonality traits, so it is useful for a clinician to understand the relationships among alternative measures. The number and content of traits describing personality vary but there is actually extensive overlap among the traits measured. Hans Eysenck popularized tests that measured three factors called Neuroticism, Extraversion, and Psychoticism.
(10) The Eysenck Personality Questionnaire also 
includes validity measure called ‘Lie’ . Nearly all tests subsequently developed include factors corresponding closely to Neuroticism and Extraversion at least. Later, Jeffrey Gray showed that individual differences in rates of learning corresponded to weighted combina-tions of Neuroticism and Extraversion.
(11) In other words, people

(11) In other words, people 
who are most prone to anxiety and respond most sensitively to punishment are neurotic introverts (that is, they are high in Neuroticism and low in Extraversion). On the other hand, people who are most impulsive and respond most sensitively to rewards are stable extraverts (that is, they are low in Neuroticism and high in Extraversion). As a result, both Zuckerman and Cloninger developed tests that correspond to these individual differences in learning and vulnerability to psychopathology, as summarized in Table 1.8.2.3. Essentially, people who are most prone to anxiety are those who are described as neurotic introverts by Eysenck, neurotic or anxiety-prone by Zuckerman and Gray, and harm-avoidant by Cloninger. On the other hand, people who are most prone to impulsivity, anger, and substance abuse are called stable extraverts 
by Eysenck, impulsive sensation-seekers by Zuckerman and Gray, 
and Novelty seekers by Cloninger.

Later, Cloninger and others showed that all seven of the dimen-
sions of his T emperament and Character Inventory had unique genetic determinants and unique brain processes, suggesting that a seven dimensional model is needed to account for the dynamic processes within each individual that regulates his personality. Nevertheless, ﬁ  ve factor models like Zuckerman and Kuhlman’s 
Personality Qeustionnaire or Costa and McCrae’s NEO personality inventory can capture most of the information about personality 
in a statistical sense, even though they ignore the non-linear structure of personality resulting from its complex evolutionary history. Tables 1.8.2.3 and 1.8.2.4 and 4 show the correlations between measures of Cloninger’s seven factor model and alterna-tive ﬁ  ve factor models (Zuckerman’s ZKPQ in Table 1.8.2.3, Costa’s

NEO-PI in Table 1.8.2.4). As in Eysenck’s Neuroticism factor, Neuroticism in ﬁ  ve factor models is a composite of anxiety-proneness 
(as measured by high Harm Avoidance) and personality disorder (as measured by low Self-directedness). Extraversion is a composite of intrapsychic processes involving risk-taking (as measured by low Harm Avoidance), impulsivity (as measured by high Novelty Seeking), and sociability (as measured by high Reward Dependence), and personality maturity (as measured by hig h Self-direc tedness).
(12)
Essentially, Neuroticism and Extraversion are composites of traits 
leading to maladaptive and adaptive emotional styles. Five factor models now also distinguish traits related to agreeability and socia-bility (as measured by TCI Reward Dependence and Cooperativeness, low ZKPQ hostility, and high NEO agreeability). There is also con-sistent recognition of a trait variously identiﬁ  ed as conscientious-

ness, persistence, and vigorous activity, which has been identiﬁ  ed 
by a speciﬁ  c resistance to extinction of intermittently reinforced 
behaviour regulated by speciﬁ  c brain circuitry in rodents and 
humans.
(13)
Beyond these four personality traits (anxiety-proneness, impul-
sive anger-proneness, social attachment, and persistence), alterna-tive models of personality vary according to how the remaining features of personality are measured. Five factor models like the ZKPQ and NEO do not measure the personality trait underlying self-awareness, which leads to insight, creativity, and spirituality; however, this trait is measured as Self-transcendence in the TCI. Individual differences in serotonergic receptor function has been found to be strongly related to Self-transcendence.
(14)
No consensus is possible to choose among alternative structures 
derived from factor analysis because an inﬁ  nity of alternative rota-

(14)
tions are statistically equivalent. Information beyond statistics is needed to choose among alternative models, as has been done by Gray, Zuckerman, and Cloninger. Such information includes brain imaging, genetics, development, or utility for developing insight 
Table 1.8.2.3  Correlations (r x 100) between the Temperament and Character Inventory (TCI) scales and those of the Eysenck Personality 
Questionnaire (EPQ-revised) and the Zuckerman-Kuhlman Personality Questionnaire (correlations over 0.4 in bold, signiﬁ  cant cor relations 
only shown, n = 207. Reprinted from Personality and Individual Differences, 21, Zuckerman, M. and Cloninger, C.R. Relationship between 
Coninger’s, Zuckerman’s, and Eysenck’s dimensions of personality, 283–5. Copyright 1996, with permission from Elsevier.

Harm avoidance Novelty seeking Reward dependence Pe rsistence Self-directed Cooperative Self-transcendent
EPQ Neuroticism 59 – 45
EPQ Extraversion – 53 44 23 18
EPQ Psychoticism 41 –45 –29 –31 – 42
EPQ Lie –21 25 34ZKPQ Neuroticism 66 –49
ZKPQ Impulsive 
Sensation–39 68 –20 28
ZKPQ Hostility –27 –32 – 60
ZKPQ Sociability –38 37 31ZKPQ Activity –29 46 361.8.2 assessment of personality

SECTION 1  the subject matter of and approach to psychiatry 82
into intrapsychic processes, as described in more detail elsewhere. (7)
Fortunately, familiarity with the strong relationships among 
alternative measures will allow the clinician to interpret ﬂ  exibly 
whatever information is available.
The assessment of personality can also be based upon abnormal 
traits indicative of personality disorder, as has been done by Livesley and others.
(15) Whether the starting point is normal or abnormal 
personality traits, the same structure of personality is observed.(11,16)
This shows that personality disorders are particular conﬁ  gurations 
of traits that vary quantitatively in the general population, not qualitatively in discrete disorders.
Clinical assessment of personality

Personality can be well assessed by allowing the patient to tell his life story and conducting a standard mental status examination. A checklist of signs and symptoms is not adequate for the assessment of personality because narratives only provide an account of a per-son’s continuity of self-awareness over his lifespan. Within the life story, the key elements on which temperament ratings are made are the narrative account of emotional style, particularly in childhood, and general appearance and behaviour on mental status examina-
tion. The key elements on which character ratings are based are the 
range of a person’s thoughts, the nature of his interpersonal rela-tionships, and his insight and judgment. The clinician must con-sider not only the words of the patient, which may involve little or

no cognitive insight or self-awareness, but also recognize the sig-
niﬁ cance of non-verbal signs from body posture, facial expression, 
and gestures to understand his way of perceiving and relating to others.
The level of a person’s foresight reﬂ  ects all of these other sources 
of information. Lack of foresight is the cardinal feature of person-ality disorder. Other consistent features of personality disorders are summarized in Table 1.8.2.5.
T emperament involves emotional biases that can be directly 
observed and felt by an experienced clinician. The tendency of a person to elicit strong emotions from others or ‘to get under the skin’ of another is a sign of extreme temperament traits or person-ality disorder. For example, the person with extreme temperament may elicit an urge to be rescued or hostility in the examiner. His 
general appearance and behavior may be ingratiating or negativistic. 
Speciﬁ  c features of temperament that distinguish subtypes of

Speciﬁ  c features of temperament that distinguish subtypes of 
personality disorders are summarized in Table 1.8.2.6.Character traits are assessed partly on intuitive recognition and 
partly on history. A person who frequently blames others or elicits strong emotional responses in the examiner should be suspected of having a personality disorder. The ratings of character are more precisely based on observations of key functions of self-awareness obtained in the life narrative and the mental status examination. The most informative ﬁ  nding concerns the level of a person’s 
self-awareness, as described in Table 1.8.2.7. The presence of per-sonality disorder means essentially that a person is usually not self-aware (stage 0 in Tab le 1.8.2.7). M ost adults are in the ﬁ  rst 
stage of self-awar eness most of the time: they are responsible, 
have initiative, and are able to delay gratiﬁ  cation if they want, but

have initiative, and are able to delay gratiﬁ  cation if they want, but 
are egocentric. As previously mentioned, they are preoccupied with material concerns. Such individuals may have problems with jealousy or pride, but are sufﬁ  ciently self-aware so that they are 
not considered personality disordered. Elsewhere, a simple exercise to evaluate level of self-awareness is described as the Silence of the Mind meditation.
(7) It can also be used to help a person improve 
his level of self-awareness, so it is useful for both assessment and treatment. The ability to reach the second or third stage of self-awareness is the key to improvement in psychotherapy, as described in detail elsewhere.
(3) Such growth in self-awareness or Table 1.8.2.4  Correlations between the scales of Temperament and Character Inventory-Revised (TCI-R) and the NEO-PI-Revised (correlations

(3) Such growth in self-awareness or Table 1.8.2.4  Correlations between the scales of Temperament and Character Inventory-Revised (TCI-R) and the NEO-PI-Revised (correlations 
over 0.4 in bold, signiﬁ  cant correlations only shown, multiple correlation also shown, n = 662, adults in the USA)
Harm avoidance Novelty seeking Reward dependence Persistence Self-directed Cooperative Self-transcendent mR
NEO Neuroticism 63 –20 – 62 –28 75
NEO Extraversion – 55 40 52 40 25 22 77
NEO Openness –25 43 25 37 54
NEO Conscience –26 –34 51 41 70
NEO Agreeability –23 40 31 61 20 66
mR 76 65 68 60 67 65 45
Table 1.8.2.5  Qualitative description of personality disorders
Discriminating features
 A maladaptive pattern of responses to personal and social stress that is
  stable and enduring since teens
  inﬂ  exible and pervasive
  causing subjective distress  and/or impaired work and/or social relations
Consistent features
  lack of foresight (that is, the ability to anticipate what will be satisfying

causing subjective distress  and/or impaired work and/or social relations
  lack of foresight (that is, the ability to anticipate what will be satisfying 
   in the long run)
  strong emotional reactions elicited from others 
 (like anger or urge to rescue)
  efforts to blame and change others, rather than oneself
Variable features
  odd, eccentric  erratic, impulsive  anxious, fearful

83
character traits corresponds closely to the stages of cognitive and 
character development as described by Piaget, Freud, and Erikson (Table 1.8.2.8). For example, the ﬁ  rst stage of self-awareness corre-
sponds to the presence of initiative in Erikson’s terms. The second stage involves the presence of generativity. More ﬁ  ne-grained 
ways to quantify the range of a person’s thoughts and human relationships are also described elsewhere.
(3) Such reﬁ  ned ratings 
are important for treatment but not for initial diagnosis.Insight and judgment are also important for assessing character

are important for treatment but not for initial diagnosis.Insight and judgment are also important for assessing character 
because they are really simply alternative terms for describing the character traits of Self-transcendence and Cooperativeness, as pre-viously discussed. The person’s history about his family of rearing, education, marriage, and work history provide the key information for evaluating character. It is important to inquire about a person’s goals and his hobbies and recreational activities, whether someone has secure friends, particularly anyone they fully trust and can conﬁ  de in now or in the past, is important to know as a measure of 
capacity for intimacy and as a predictor of capacity for forming a therapeutic alliance. Relationships with prior counselors, as well as history of disability claims and law-suits provide important infor-mation about personality.
Remember that it is often important with psychiatric patients to

Remember that it is often important with psychiatric patients to 
assess their personality when they were children or adolescents. In other words, it is as important to evaluate their personality retro-spectively as well as in practical, particularly at an age before the onset of other psychopathology, like substance abuse or depression. Current anxiety or depression is expected to inﬂ  ate Harm Avoidance 
ratings. Stress or intoxication tends to release temperaments from higher cortical control by character. Likewise, chronic substance abuse, depression, or psychosis arrest character development while active, so early onset of mental disorders is often associated with character deﬁ  cits. It is usually easy for a patient to provide mean-
ingful information about his childhood personality if the clinician simply asks about the child’s early relationships with parents, 
siblings, schoolmates, and other childhood friends.
Remember also that the single most important dimension of

Remember also that the single most important dimension of 
personality to assess in rating a person’s level of maturity is his degree of foresight, measured as his Self-directedness. Is the person responsible, or does he tend to blame his problems on other people on unfortunate circumstances? Is the person purposeful, or does he lack clear goals in his life? Is he resourceful, or does he feel inade-quate himself and depends on others to solve his problems for him? Assessment of Self-directedness alone is sufﬁ  cient to determine if a 
person has a personality disorder of at least moderate severity.
(2,4)
In contrast, the ﬁ  nding of high Neuroticism is not the same as 
ﬁ nding of low Self-directedness, even though they are strongly 
correlated: a person with anxiety or mood disorder and no personality disorder may be high in Neuroticism but not low in Self-directedness.
Some mild personality disorders also require consideration of

Some mild personality disorders also require consideration of 
the person’s capacity to get along with others, as measured by his Cooperativeness. In addition, high functioning individuals who do not merit a diagnosis of personality disorder may nevertheless have speciﬁ  c blind spots in their insight and judgment that leads 
to severe problems. For example, a competent physician may usu-ally be self-aware but lacks a capacity for intimacy or a sense of fairness in business. Such speciﬁ  c deﬁ  cits may have severe impair-
ment, even if a person is self-aware in other situations. As a result, 
it is important to consider the overall proﬁ  le of a person’s life in 
all ﬁ ve types of situations mentioned earlier. Simply deciding 
whether or not a person has a personality disorder is insufﬁ  cient 
for an assessment of his personality and risk for psychopathology.

for an assessment of his personality and risk for psychopathology. 
An adequate initial assessment of a person’s personality should allow ratings of all four dimensions of temperament and three dimensions of character, which in turn provide a basis for under-standing a person’s capacity for well-being and vulnerability to psychopathology.Table 1.8.2.7  Three stages of self-awareness on the path to well-
being (Reproduced from Cloniger, C.R. (2004). Feeling Good: The 
Science of Well Being , with permission of Oxford University Press, 
New York)
Stage Description Psychological characteristics
0 unaware irresponsible, seeking immediate gratiﬁ  cation
(‘child-like’ ego-state)
1 average adult purposeful but egocentric
cognition able to delay gratiﬁ  cation, but has frequent negative
emotions (anxiety, anger, disgust)
(‘adult’ ego-state)
2 meta-cognition resourceful and allocentric

aware of own subconscious thinkingcalm and patient,so able to supervise conﬂ  icts and relationships(‘parental’ ego-state, ‘mindfulness’)
3 contemplation creative and holistic perspective
wise, spontaneous, and lovingable to access what was previously unconscious
 as needed without effort or distress
able to anticipate what will be satisfying in future(‘state of well-being’, ‘foresight’)Table 1.8.2.6  Qualitative clusters and subtypes of personality 
disorders according to the American Psychiatric Association (DSM-IV, 1994)
Cluster Subtype Discriminating 
features
Odd/Eccentric (Low Reward Dependence)
Schizoid socially indifferent
Paranoid suspicious
Schizotypal eccentric
Erratic/Impulsive (High Novelty Seeking)
Antisocial disagreeable
Borderline unstable
Histrionic attention-seeking
Narcissistic self-centered

Anxious/Fearful (High Harm Avoidance)
Avoidant inhibitedDependent submissive
Obsessive perfectionistic
Not otherwise speciﬁ  ed
Passive-Aggressive negativistic
Depressive pessimistic1.8.2 assessment of personality

SECTION 1  the subject matter of and approach to psychiatry 84
Clinical value of psychometric testing
Most experienced clinicians should be able to make valid personality 
assessments without psychometric testing. However, psychometric testing may still be useful for at least three reasons. First, it helps the clinician to reﬁ  ne his or her clinical assessments by asking more 
questions with comparisons to normative data than is usually practical during a clinical session. Second, it provides the patient written feedback that can be studied and reﬂ  ected upon, which 
does not depend on the clinicians’ subjective biases—it reﬂ  ects

does not depend on the clinicians’ subjective biases—it reﬂ  ects 
back to the patient what was said and provides a language that can be used for accurate communication between the patient and the doctor. Third, it provides a standard for comparison to later assessments as a means of measuring growth. As a result, it is often useful to supplement clinical impression with documentation that allows the patient to describe himself or herself without reliance 
on the judgment of anyone else. The patient’s effort to describe 
himself or herself often has the therapeutic value of stimulating the patient to begin to understand the motives underlying the pattern of his behaviour. In addition, comparison of psychometric test scores with clinical impression is a helpful way for the clinicians to train themselves in the art of personality assessment.
The Washington University Center for Well-Being: psychobiology.wustl.edu
The Anthropaideia Foundation: aidwellbeing.org

 1. Kaasinen, V ., and Aalto, S. et al. (2004). Insular dopamine D2 receptors 
and novelty seeking personality in Parkinson’s disease. Movement 
Disorders ,19(11), 1348–51. 2. Cloninger, C. R. (2000). A practical way to diagnose personality 
disorder: A proposal. Journal of Personality Disorders ,14(2), 
99–108.
 3. Joyce, P . R., Mulder, R. T. et al. (1994). T emperament predicts 
clomipramine and desipramine response in major depression. Journal of Affective Disorders ,30, 35–46.
 4. Cloninger, C. R., Svrakic, D. M. et al. (1993). A psychobiological 
model of temperament and character. Archives of General Psychiatry ,
50, 975–90.
 5. Joyce, P . R., Mulder, R. T. et al. (2003). Borderline personality 
disorder in major depression: differential drug response, and 6-month outcome. Comprehensive Psychiatry ,44(1), 35–43.

5. Joyce, P . R., Mulder, R. T. et al. (2003). Borderline personality 
 6. Oldham, J. M., Gabbard, G. O. et al. (2001). Practice guidelines for the 
treatment of patients with borderline personality disorder . Washington, 
DC., American Psychiatric Press.
 7. Cloninger, C. R. (2004). Feeling Good: The Science of Well Being .
New Y ork, Oxford University Press.
 8. Perls, F. S. (1969). Gestalt Therapy Verbatim . Lafayette, California, Real 
People Press.
 9. Lowen, A. (2003). The language of the body: Physical dynamics of 
character structure . Alchua, Florida, Bioenergetics Press.
10. Eysenck, H. J., (ed.) (1981). A Model of Personality . New York, 
Springer-Verlag.
11. Gray, J. A. (1981). A critique of Eysenck’s Theory of Personality. 
A Model of Personality . H. J. Eysenck. New Y ork, Springer-Verlag: 
246–76.

246–76.
12. Zuckerman, M. and Cloninger, C. R. (1996). Relationships between 
Cloninger’s, Zuckerman’s, and Eysenck’s dimensions of personality.Personality & Individual Differences ,21, 283–5.
13. Gusnard, D. A., Ollinger, J. M. et al. (2003). Persistence and brain 
circuitry. Proceedings of the National Academy of Sciences USA ,
100(6), 3479–84.
14. Borg, J., Andree, B. et al. (2003). The serotonin system and spiritual 
experiences. American Journal of Psychiatry ,160(11), 
1965–1969.Table 1.8.2.8  Comparison of different descriptions of character development
Stage of character 
developmentStage of Piaget Stage of Freud Stage of Erikson Judgment 
(Cooperative)Insight 
(Self-Transcendent)Foresight 
(Self-directed)
 0 Reﬂ  exive
 1 Enactive Tolerance 2O r a l T r u s t T r u s t 3 Responsible

 0 Reﬂ  exive
 4 Intuitive Anal Autonomy Forgiving 5 Phallic Initiative Free-Flowing Productivity 6 Concrete
OperationsLatency Industry Purposeful
 7 Early Genital Empathic
 8 Transpersonal Identiﬁ  cation
 9 Abstract Operations Identity Resilient10 Later Genital Intimacy Helpful11 Keeper of Meaning Creativity12 Resourceful
13 Integrity Principled14 Holistic Intuition
15 Spontaneous

85
15. Livesley, W. J., Jang, K. L. et al. (1998). Phenotypic and genetic structure 
of traits delineating personality disorder. Archives of General Psychiatry
55, 941–48.
16. Strack, S., (ed.) (2006). Differentiating normal and abnormal 
personality . Springer Publishing, New Y ork.
1.8.3 Cognitive assessment
Principles of assessment
Assessment, testing, or measurement is the evaluation of the indi-

vidual in numerical or categorical terms, adhering to a range of statistical and psychometric principles. Examples of measurement are, assigning people or behaviour to categories, using scales to obtain self-ratings or self-reports, using tests of ability and perfor-mance, or collecting psychophysiological readings. Even diagnosis is a form of measurement and should have various psychometric properties such as satisfactory reliability and validity. In this chapter we concentrate on cognitive or neuropsychological assess-ment, which typically employs standardized psychometric tests, but it is axiomatic that the basic principles are applicable to all forms of measurement without exception. For example, stating that a patient does or does not have a symptom is potentially just as much of a measurement as stating his or her IQ. It should be noted

that this account is of English language tests, and readers elsewhere should note the principles but ask local psychologists what tests 
they use.
Psychometric tests aim to measure a real quantity—the degree 
to which an individual possesses or does not possess some feature or trait, such as social anxiety or spelling ability or spatial memo-ry. This real quantity is known in classical test theory as the true 
score t, and the score that is actually obtained on the given test is 
the observed score x. It is assumed that the observed score is a 
function of two values, the true score plus a certain amount of error e, because no test is perfect. Therefore we have the most 
basic equation in psychometrics: x = t + e. The statistical aim of

basic equation in psychometrics: x = t + e. The statistical aim of 
psychometric measurement is to keep the error term to an abso-lute minimum so that the observed score is equal to the true score, which happens when the error term is reduced to zero. Of course, this is never achieved, but the error term can be reduced to the minimum by making the test as reliable as possible, where reliability is simply the notion that the test gives the same answer twice.
In practice, of course, if a test were repeated many times, each

In practice, of course, if a test were repeated many times, each 
occasion would give a slightly different result, depending on how the person felt, the precise way questions were asked, the details of how answers were scored, or whether there has been any lucky guessing. In other words, observed scores would cluster around the true score. Like the distribution of any variable, the distribution of observed scores would have a mean and a standard deviation. The mean is obviously the true score, and this standard deviation is called the standard error of measurement (SEM) . The aim of a 
good test is to keep the SEM as near as possible to zero, and test 
manuals should state the actual SEM.There is a relationship between SEM and the reliability of the 
test:
 SEM = SD √(1 − r
11)
where SD is the standard deviation of the test and r11 is the test–
retest reliability of the test (expressed as a correlation coefﬁ  cient

test:
11)
retest reliability of the test (expressed as a correlation coefﬁ  cient 
ranging from −1 to +1). If the reliability of the test is perfect (+1), as can be seen the SEM will be zero:
 SEM = SD √(1−1) = SD √0 = 0.
Thus a test should be as reliable as possible because then the 
observed score will be the true score and the standard error of measurement will be zero.
An unreliable test is always useless, but if reliability can be 
achieved then it is worth considering the test score and, more speciﬁ  cally, what it measures. The degree to which a test measures 
what it is supposed to measure is known as validity . There may be

what it is supposed to measure is known as validity . There may be 
various threats to validity. For example, a test of numeracy may be so stressful that scores are highly dependent upon the patient’s anxiety level rather than on his or her ability, or a test of social comprehension may have questions which are culturally biased and so scores may depend in part upon the person’s ethnic background.
In practice, there are various types of reliability and validity, 
and these are summarized in Tables 1.8.3.1 and 1.8.3.2. Further dis-cussion can be found in Kline.
(1)
Having used a reliable and valid test, the next issue is how the 
numbers are analysed and expressed. It has to be noted ﬁ  rst that 
there are three types of scale of measurement. A nominal  scale is

there are three types of scale of measurement. A nominal  scale is 
when numbers are assigned to various categories simply to label the categories in a manner suitable for entry onto a computer database—the categories actually bear no logical numerical rela-tionship to each other. Examples would be marital test status or ethnic background or whether one’s parents were divorced or not. Nominal scales are used to split people into groups and all statistics 1.8.3 cognitive assessment
Table 1.8.3.1  Types of reliability
Scorer or rater 
reliabilityThe probability that two judges will (i) give the same score 
to a given answer, (ii) rate a given behaviour in the same 
way, or (iii) add up the score properly. Scorer reliability 
should be near perfect.
Test–retest 
reliabilityThe degree to which a test will give the same result on 
two different occasions separated in time, normally

two different occasions separated in time, normally 
expressed as a correlation coefﬁ  cient. A reliability of 
less than 0.8 is dubious.
Parallel-form 
reliabilityThe degree to which two equivalent versions of a test give 
the same result (usually used when a test cannot be exactly 
repeated because, say, of large practice effects).
Split-half 
reliabilityIf a test cannot be repeated and there are no parallel forms, 
a test can be notionally split in two and the two halves 
correlated with each other (e.g. odd items versus even 
items). There is also a mathematical formula for computing the mean of all possible split halves (the Kuder–Richardson 
method).
Internal 
consistencyThe degree to which one test item correlates with all 
other test items, i.e. an ‘intraclass correlation’ such as the a 
coefﬁ  cient, which should not drop below 0.7.

SECTION 1  the subject matter of and approach to psychiatry 86
are based on the frequency of people in each group. The relation-
ship or association between groups can be examined using χ2
statistics, for example to test whether there is a relationship between 
being divorced and having parents who divorced. Next there is an 
ordinal  scale, in which larger numbers indicate greater possession 
of the property in question. Rather like the order of winning a race, no assumptions are made about the magnitude of the difference between any two scale points; it does not matter whether the race is won by an inch or a mile. Ordinal scales allow people to be rank ordered and numerical scales can be subjected to non-parametric statistical analysis (which is that branch of statistics which makes minimal assumptions about intervals and distributions), including the comparison of means and distributions and the computation of certain correlation coefﬁ  cients. Finally comes the interval  scale

in which each scale point is a ﬁ  xed interval from the previous one, 
like height or speed. The types of test described in this chapter for 
the most part aspire to be interval scales, allowing use of the full 
range of parametric statistics (which assume equal intervals and normally distributed variables).
Having obtained a test score for someone, that score then has to 
be interpreted in the light of how the general population or various patient groups generally perform on that test. There are two gen-eral characteristics of a scale that have to be remembered. The ﬁ  rst is the measure of central tendency. Typically one would consider 
the mean (the arithmetic average), but it is also sometimes useful to consider the median (the middle score) and the mode (the most frequently obtained score). This will be the ﬁ  rst hint as to whether

the score is normal or whether it is more typical of one group than another. However, in order to gauge precisely how typical a given score is, it is necessary to take into account the standard deviation 
(SD)  of the test (other measures relating to the dispersion of test 
scores, such as the range or skew, can be considered but are not of such immediate relevance).
As long as the mean and SD of the test are known, it is possible to 
work out exactly what percentage of people obtain up to the observed score x. This is done by converting the observed score 
into a standard score z and converting the z-score to a percentile .
A standard score is simply the number of SDs away from the mean m, and it will have both negative and positive values (because an 
observed score can be either below or above the mean, respectively). In other words, z = (x−m)/SD. For reference, Table 1.8.3.3 gives 
some of the main values of z and what percentage of people score

some of the main values of z and what percentage of people score 
up to those values. It is this percentage that is known as the percen-tile and it is obtained from statistical tables. For example, a score at the 25th percentile means that 25 per cent of people score lower than that speciﬁ  c score. Obviously, the 50th percentile is the mean 
of the test. For illustration, the equivalent IQ scores (IQ scores have a mean of 100 and SD of 15) and broad verbal descriptors are also given in Table 1.8.3.3.
A knowledge of percentile scores can help to decide to which 
category a patient may belong. For example, if a patient completes a token test of dysphasia and scores at the 5th percentile for normal controls and the 63rd percentile for a group of dysphasics, the score is clearly more typical of the dysphasic group.
However, in clinical practice it is often not just a comparison

However, in clinical practice it is often not just a comparison 
with others that is needed, but a comparison between two of the patient’s own scores. For example, verbal IQ might seem depressed Table 1.8.3.2 Types of validity
Face validity Whether a test seems sensible to the person completing it; i.e. 
does it appear to measure what it is meant to be measuring? 
This is in fact not a statistical concept, but without reasonable 
face validity, a patient may see little point in co-operating with 
a test that seems stupid.
Content 
validityThe degree to which the test measures all the aspects of the 
quality that is being assessed. Again, this is not a statistical 
concept but more a question of expert judgement.
Concurrent 
validityWhether scores on a test discriminate between people who 
are differentiated on some criterion (e.g. are scores on a test of neuroticism higher in those people with a neurotic disorder 
than in those without such a disorder!). Also, whether scores

than in those without such a disorder!). Also, whether scores 
on a test correlate with scores on a test known to measure the same or similar quality.
Predictive 
validityThe degree to which a test predicts whether some criterion is 
achieved in the future (e.g. whether a child’s IQ test predicts 
adult occupational success; whether a test of psychological coping predicts later psychiatric breakdown). For obvious 
reasons, these last two types of validity are often jointly 
referred to as criterion-reiated validity.
Construct 
validityWhether a test measures some speciﬁ  ed hypothetical 
construct, i.e. the ‘meaning’ of test scores. For example, if a test 
is measuring one construct, there should not be clusters of 
items that seem to measure different things; the test should 
correlate with other measures of the construct ( convergent

correlate with other measures of the construct ( convergent 
validity ); it should not correlate with measures that are 
irrelevant to the construct ( divergent validity ).
Factorial 
validityIf a test breaks down into various subfactors, then the number 
and nature of these factors should remain stable across time 
and different subject populations.
Incremental 
validityWhether the test result improves decision-making (e.g. 
whether knowledge of neuropsychological test results 
improves the detection of brain injury).
Table 1.8.3.3  z-scores, percentiles, IQ scores, and descriptions
z-score Percentile IQ Description
–2.00 2.5th 70 Scores below the 2.5th percentile are 
deﬁ  cient or in the mentally retarded range
–1.67 5th 75–1.33 10th 80 Scores between the 2.5th and 10th 
percentile are borderline
–1.00 16th 85–0.67 25th 90 Scores between the 10th and 25th

–1.00 16th 85–0.67 25th 90 Scores between the 10th and 25th 
percentile are low average
–0.33 37th 95
0.00 50th 100 The mean score
+0.33 63rd 105+0.67 75th 110 Scores between the 25th and 75th 
percentile are in the average range
+1.00 84th 115
1.33 90th 120 Scores between the 75th and 90th 
percentile are high average
120+ Scores over the 90th percentile are superior

87
in comparison with spatial IQ, or the patient’s memory quotient 
might seem too low for his or her IQ. These are known as difference 
scores , and their analysis is a crucial part of the statistical analysis of 
a patient’s proﬁ  le. There are two key concepts: the reliability of dif-
ference scores  and the abnormality of difference scores . Failure to 
distinguish between these two leads to all manner of erroneous con-clusions. In brief, a reliable difference is one that is unlikely to be due to chance factors, so that if the person were to be retested then the difference would again be found. If the test is very reliable (see the previous discussion of reliability), even a small difference score, may be reliable. As a concrete example, the manual of the Wechsler Adult Intelligence Scale—Third Edition ( W AIS-III )
(1) indicates that 
a difference of about nine points between verbal IQ and perfor-mance IQ is statistically reliable at the 95 per cent level of certainty.

However, although a difference of this size would be reliable, this 
does not necessarily mean that it is abnormal and therefore indica-tive of pathology. The abnormality of a difference score is the per-centage of the general population that has a difference score of this size or greater. Published tables,
(2) show that 18 per cent of adults 
have a discrepancy of at least 10 points between verbal and perfor-mance IQ, so a difference of 10 points is not at all unusual. In fact, to obtain an abnormal difference between verbal and performance IQ the discrepancy has to be of the order of 22 points for adults and 26 points for children (i.e. less than 5 per cent of adults or chil-dren have discrepancy scores of this size).
Having introduced the basic concepts of psychometric assess-

ment, this is an appropriate point, prior to the description of speciﬁ  c tests, at which to summarize the information that can 
(or should) be found in a typical test manual, and this is set out in Table 1.8.3.4.
Tests of cognitive and neuropsychological 
functioning
General ability and intelligence
A very useful broad screening test, especially when it is suspected that
mental functions are severely compromised, is the Mini-Mental State Examination.
(3,4) It is brief, to the point, and can be repeated

(3,4) It is brief, to the point, and can be repeated 
over time to gauge change. It measures general orientation in time and place, basic naming, language and memory functions, and basic non-verbal skills, and has good norms for a middle age range, especially the elderly, with appropriate adjustment for age. The maximum score is 30, and a score of 24 or less raises the possibility of dementia in older persons, especially if they have had nine or more years of education (a score of 24 is at about the 10th percen-tile for people aged 65 and older).
However, the Mini-Mental State Examination is only a screening 
test and the presence or nature of cognitive impairment cannot be diagnosed on the basis of this test alone. A detailed cognitive assessment is provided by the Wechsler scales, i.e. the Wechsler Adult Intelligence Scale—Third Edition UK Version ( W AIS-III
UK),(1)

UK),(1)
the Wechsler Intelligence Scale for Children—IV UK Version 
(WISC-IVUK),(5) or the Wechsler Preschool and Primary Scale of 
Intelligence—Revised ( WPPSI-III ).(6) Outlines of the WAIS-IIIUK
and WISC-IVUK are given in Table 1.8.3.5.
IQ scores themselves are very broad measures, drawing upon a 
wide range of functions. This does not only mean that the scores are very stable (reliable), but also that the IQ score is relatively insensitive to anything except quite gross brain damage. Rather, a 
careful analysis of subtest scores is needed, always bearing in mind the concepts of reliability and abnormality of difference scores. For example, it takes a subtest range of 11 to 12 points to be considered abnormal (i.e. found in less than 5 per cent of people) on the WAIS-III
UK and the WISC-IVUK.
Sometimes the patient may have a language disorder or English 
may not be his or her ﬁ  rst language. In such circumstances Raven’s

may not be his or her ﬁ  rst language. In such circumstances Raven’s 
Progressive Matrices T est,(7) which is a non-verbal test of inductive 
reasoning (non-verbal in the sense that it requires no verbal instructions and no verbal or written answers), can be used. The present author avoids the new norms because they were not col-lected in the normal fashion (i.e. not in a formal test session under the direct supervision of a psychologist), but the old norms are good. The Matrices T est has the additional advantage of having an advanced version for people in the highest range of ability.
(8) No 
non-English versions of the WAIS-IIIUK or the WISC-IVUK are 
available, but the non-verbal scores can be used with caution as there may be unexpected cross-cultural effects.
Speed of processing
Reasoning is not just about solving difﬁ  cult problems, but also

Reasoning is not just about solving difﬁ  cult problems, but also 
about solving them quickly; the difference between power and speed. IQ tests as above do have timed subtests sensitive to speed, but it can be useful to administer speciﬁ  c tests that are not quite so 
confounded with intellectual ability.
One example, particularly sensitive to even quite mild concussion, 
is the Paced Auditory Serial Addition T est ( PASAT ).
(9,10) Here, the Table 1.8.3.4  What to expect in a good test manual
Theory The history of the development of the concept and earlier 
 versions of the test
The nature of the construct and the purpose of measuring it
Standardization Characteristics of the standardization sample, how the 
 sampling was carried out. and how well these 
 characteristics match those of the general populationSimilar data on any criterion groups

sampling was carried out. and how well these 
Similar data for each age range if the test is for children
Administration How to administer the test in a standard fashion so as to 
 minimize variability of administration as a factor in the  error term
Scoring How to score the test, and criteria for awarding different 
 scores, so as to minimize scorer error
Statistical 
propertiesMeans and standard deviations of all groups
Reliability coefﬁ  cients and how they were obtainedValidity measures and how they were derived
Standard error of measurement
Reliability of difference scoresAbnormality of difference scores
Other data on the scatter of subtest scores
Scores of criterion groups
Special 
considerationsGroups for whom the test is not suitable or less suitable, 
 i.e. the range of convenience of the tests
Ceiling effects: at what point does the test begin to fail to

Special 
Ceiling effects: at what point does the test begin to fail to 
 discriminate between high scorers?
Floor effects: at what point does the test begin to fail to 
 discriminate between low scorers?1.8.3 cognitive assessment

SECTION 1  the subject matter of and approach to psychiatry 88
client is read a list of numbers, and as each one is read out so it has to 
be added to the previous number and the answer spoken aloud (Table 1.8.3.6). This has to be done quickly or the next number will come along. There are several trials in which the numbers are deliv-
ered at a faster and faster pace, from one number every 2.4 s down to 
every 1.2 s. It sounds easy but in actuality is very demanding; even at 
the slowest speed the average score is only about 70 per cent correct, and this falls away to only about 40 per cent at the fastest speed. Indeed, if a patient has any signiﬁ  cant mental slowing, they often 
cannot do the test at all. Obviously the test cannot be used if the patient has a stammer, or is dysarthric or innumerate.
A less stressful test of mental speed is the Speed of Comprehension 
T est,
(11) in which the person indicates as fast as possible whether sim-

T est,
ple sentences are true or false (e.g. tomato soup is a liquid, grapes are people). The test can be given orally for patients who cannot read.
Two visual tests of mental speed are Map Search (looking for target 
symbols on a map as fast as possible) and T elephone Search (look-
ing for various symbols on a page from a telephone directory).
(12)
One test that tries to disentangle the relative contribution of 
slowed motor speed versus slowed mental speed, often a crucial issue in patients with motor deﬁ  cits, is the Adult Memory and 
Information Processing Battery,(13) which has two useful timed 
tests of cancelling target digits.
Attention and concentration

There are various aspects of attention and concentration: the ability to focus resources, the ability to focus on the right aspect, the ability to sustain this attention, the ability to ignore extraneous Table 1.8.3.5  Outline of the WAIS-III
UK and WISC -IVUK
WAIS-IIIUKWISC -IVUK
Age range 16–89 years 6.0–16.11 years
Verbal subtests Vocabulary Similarities
Similarities Digit span
Arithmetic Vocabulary
Digit span Letter-number sequencing
Information ComprehensionComprehension Information
Letter-number sequencing Arithmetic
Word reasoning
Non-verbal or spatial subtests Picture completion Block design
Digit symbol Picture concepts
Block design Coding
Matrix reasoning Matrix reasoningPicture arrangement Symbol search
Symbol search Picture completion
Object assembly Cancellation
IQ score Verbal IQ (VIQ) Full scale IQ (FSIQ)
Performance IQ (PIQ)

Full scale IQ (FSIQ)
Index scores Verbal comprehension Verbal comprehension
Perceptual organization Perceptual reasoning
Working memory Freedom from distractibilityProcessing speed Processing speed
Mean IQ or index scores 100 (SD of 15) 100 (SD of 15)
Mean subtest scores 10 (SD of 3) 10 (SD of 3)Test–retest reliability of IQ 0.98 for Full scale IQ 0.97 for Full scale IQStandard error of measurement of FSIQ About 2.5, so all scores are about ±5 points
aAbout 2.68, so all scores are about ±5 points
Reliable differences ( p <.05) About 9 points between VIQ and PIQ About 11 points between VCI and PRI
Abnormal differences ( p <.05) About 22 points between VIQ and PIQ About 26 points between VCI and PRI
Validity Highly related to other tests of ability and to criteria

Validity Highly related to other tests of ability and to criteria 
related to abilityHighly related to other tests of ability and to 
criterion groups
a95% of the time, true scores are the observed score ±1.96 SEM. In other words, the likely true score is within the range deﬁ  ned by about 2 SEMs either side of the score obtained.
Table 1.8.3.6  Sample from PASAT
Number on tape (Mental process) Patient says
7
5 (5+7) 121 (1+5) 64 (4+1) 59 (9+4) 13

89
information or distracting events, and the ability to divide atten-
tion between different tasks. The tests on speed listed above are of course also measures of attention, because highly focused and selective attention has to be sustained for the duration of a pressured task. Digit span on the WAIS-III
UK is also a test of attention, as any 
lapse in attending to the incoming digits will necessarily result in a wrong answer.
However, in addition to these tests, a battery may be used, such 
as the T est of Everyday Attention
(12) which has eight different 
subtests. T est–retest reliability is quite good, over 0.83 for Map Search and T elephone Search, for example. In terms of validity, the tests are very sensitive to the effects of head injury and stroke.
Memory

Memory
Memory is a complex set of processes whereby the person registers, stores, and retrieves information within different modalities (e.g. verbal memory versus spatial memory) and across different time periods (e.g. primary or shorter-term memory versus secondary or longer-term memory or learning). Therefore, as with intelligence, various batteries have evolved with subtests that tap these various aspects. Two examples of batteries are the Wechsler Memory Scale—Third Edition
(14) for adults and the Children’s Memory 
Scale,(15) which are both summarized in Table 1.8.3.7. Another bat-
tery, which makes a special effort to reﬂ  ect real-life tasks, is the 
Rivermead Behavioural Memory T est,(16) which also has a child’s 
version.(17)
Sometimes time constraints make it difﬁ  cult to give complete

Sometimes time constraints make it difﬁ  cult to give complete 
memory batteries. Often, just a few key subtests are selected, or other individual tests may be given. For example, to gauge verbal learning the Rey Auditory-Verbal Learning T est is well researched,
(18)
a test of visual memory is the Rey–Osterrieth Complex Figure T est
(19); and a forced choice recognition tests for words and faces is 
the Recognition Memory T est.(20) If the ability of the patient to 
recall details of his or her past life is an issue, the Autobiographical Memory Interview can be used.
(21)
Language
Commonly used batteries for the assessment of language deﬁ  cits 
are the Boston Diagnostic Aphasia Examination(22) and the closely 
related Western Aphasia Battery.(23) The Boston Examination

related Western Aphasia Battery.(23) The Boston Examination 
covers auditory comprehension, oral expression, understanding written language, and writing. These tests can take a long time to give and so brief screening tests are often used, such as the Boston Naming T est
(24) or the Graded Naming T est,(25) which both assess 
word ﬁ  nding, or the T oken T est,(26) which assesses verbal compre-
hension. Finally, a good test to gauge reading and spelling ability is the Wechsler Objective Reading Dimensions T est
(27) which will 
produce reading and spelling ages, and give the abnormality of difference scores between IQ and reading or spelling scores.
Frontal and executive functions
The term executive function derives from the theory that there is a supervisory system exerting executive control of attention. Deﬁ  cits

The term executive function derives from the theory that there is a supervisory system exerting executive control of attention. Deﬁ  cits 
of this system cause broad patterns of cognitive and behavioural 
change called the dysexecutive syndrome,
(28) which includes 
changes in volition, poor planning, a disruption of purposive action, and reduced efﬁ  cacy of performance. One of the most 
frequent causes of this syndrome is damage to the frontal lobes (frontal-lobe syndrome is a dysexecutive syndrome) but it may also 
be caused by other patterns of lesion. Table 1.8.3.8 lists some of the features of the dysexecutive syndrome, and examples of tests that are sensitive to them.
Some clinical issues
Sources of tests and test data
A good summary of the principles of test theory is given by Halligan et al.
(36) Information about tests and where to order them from can 
be found in Lezak’s Neuropsychological Assessment ,(37) Strauss’s

be found in Lezak’s Neuropsychological Assessment ,(37) Strauss’s 
Compendium of Neuropsychological Tests(2) and Mitrushina’s(38)
Handbook of Normative Data .
Understanding tests
The onus is upon the test user to be sufﬁ  ciently knowledgeable 
about test theory to gauge the strengths and limitations of tests. Common problems with tests are small standardization sample sizes, unknown or unstable factor structure, poor or no theoretical adequacy, poor or no use of criterion groups, vague scoring Table 1.8.3.7  Summary of two memory batteries
Wechsler memory
Scale-IIIChildren’s memory scale
Age range 16–89 years 5–16 years
Subtests Information and orientation
Logical memorya
Facesa
Verbal paired associatesa
Family picturesa
Word listsa
Visual reproductiona
Letter—number sequencingSpatial span
Mental control
Digit span(Means typically 10, SDs 
typically 3)Dot locations
a
Storiesa
Facesa
Word pairsa

a
Storiesa
Facesa
Numbers
Sequences
Picture locations
(Means of 10, SDs of 3)
Index Scores Auditory immediate
Visual immediate
Immediate memory
Auditory delayedVisual delayed
Auditory recognition delayed
General memory
Working memory
(Means of 100, SDs of 15)Verbal immediate
Verbal delayed
Verbal delayed recognition
LearningVisual immediate
Visual delayed
Attention/concentrationGeneral memory
(Means of 100, SDs of 15)
Reliability 0.60–0.87 for the index scores 
(i.e. rather low, and note a 
practice effect of up to 15 
points across 5 weeks)0.76–0.91 for the index 
scores (note a large practice 
effect of about 10–15 points 
across a 2-month interval)
Standard error 
of measurement3.88–7.40 (so true scores are 
at best ±8 points from the 
observed score)4.5–7.4 (so true scores are

observed score)4.5–7.4 (so true scores are 
at best ±9 points from the 
observed score)
Validity See manual for content, 
criterion-related, construct, and other types of validitySee manual for content, 
construct, and criterion-related validity
aAlso delayed trial.1.8.3 cognitive assessment

SECTION 1  the subject matter of and approach to psychiatry 90
criteria, and poor or no information on difference scores within or 
between tests.
Even a well-normed and proven test may not actually be 
applicable to the particular patient at hand; tests only have a cer-tain range of convenience. T ests have to be very carefully chosen when confounding factors are present, such as when English is not the patient’s ﬁ  rst language or when there is a sensory or motor 
deﬁ cit.
Indeed, there are a range of potentially confounding variables 
even in those patients who are within the range of convenience of the test. These include effects of medication, fatigue as the testing progresses, motivation, mental state, disturbed behaviour, cultural background and beliefs, and educational background. T est manuals may provide information on such potentially confounding vari-
ables, but often it is necessary to know the primary research on the 
test and its sensitivity to such factors.

Assessing children
Special issues arise in the assessment of children because the neu-ropsychology theory and conceptual framework are different, the effects of speciﬁ  ed lesions change with age, the pattern of recovery 
of function varies with age, extensive developmental norms, cover-ing the age range, are needed, and children may be more stressed by tests or may ﬁ  nd it harder to cooperate with test procedures. These 
and other issues are fully discussed in texts on developmental neu-ropsychology,
(39) paediatric neuropsychology,(40) and head injury 
in children.(41) Several children’s tests have already been cited by name in preceding sections, and many of the adult tests cited have

in children.(41) Several children’s tests have already been cited by name in preceding sections, and many of the adult tests cited have 
also been standardized on children, often in subsequent research studies not necessarily carried out by the original test author. Examples of tests with children’s norms are word ﬂ  uency, design 
ﬂ uency, auditory verbal learning, the original Wechsler Memory 
Scale, the Stroop T est, the T oken T est, the Trail-making T est, Wisconsin Card Sorting, the Paced Serial Addition T est, and the Progressive Matrices T est.
Assessing premorbid ability
In order to understand the effects of a brain injury, to gauge intellectual loss, to plan rehabilitation, and to advise on issues relat-ing to personal injury compensation, it is necessary to estimate premorbid intelligence. A summary of strategies for estimating premorbid IQ is given in Table 1.8.3.9.
Capacity

Capacity
Within the context of intellectual and cognitive functioning, a person is incapable of managing his or her own affairs if two Table 1.8.3.8  Features and tests of the dysexecutive syndrome
Features Tests
Behavioural change The Dysexecutive Questionnaire (DEX), both 
self-report and other report(29)
Planning and impulsivity Mazes subtest of the WISC -IVUK(7)
Fluency Of generating words and designs, the DKEFS(30)
Concept formations and 
ability to shift mental setModiﬁ  ed Card Sorting Test(31) 
Rule Shift Cards Test(33)
Estimation Of various amounts, the Cognitive 
Estimates Test(32,33)
Temporal Judgement Test of time estimation
(29)
Alternating plans Switching between plans based on numbers or 
letters, the Trail Making Test, see DKEFS(30)
Screening out distracting informationThe Stroop Test,
(34) e.g. reading the word 
‘BLUE’ when it is printed in red ink
Suppression of competing 
responsesThe Hayling Test(35) which requires patients to

responsesThe Hayling Test(35) which requires patients to 
choose connected or unconnected words to 
ﬁ  nish a sentence
Rule attainment Brixton Test, requiring the patient to learn the 
rule whereby a pattern changes(35)
Planning Action Program Test, to use given materials to 
achieve a given end(29) 
Zoo Map Test of organizing a route(29)
Modiﬁ  ed Six Elements Test of planning the 
order of tasks according to rules(29)Table 1.8.3.9  Strategies for estimating premorbid IQ
Strategy Test and/or comment
Assume highest subtest 
score on the WAIS-III 
represents original levelNormal individuals have a proﬁ  le of abilities 
and show quite a wide range of subtest scores. 
It makes no sense at all to say that a person’s 
best score is his or her ‘real’ potential. Anyone using this method will grossly over-estimate 
IQ loss
Consider scores on subtests 
thought to be relatively

IQ loss
thought to be relatively 
insensitive to the effects of 
brain injuryVocabulary is highly correlated with IQ and 
is also such a deeply ingrained ability that it 
is relatively insensitive to the affects of brain 
injury. Therefore, scores on the Vocabulary subtest can indeed be a guide to premorbid IQ
Gauge IQ from educational 
recordThis is reasonable as long as the person had (i) 
full access to education, and (ii) the motivation 
to take and pass exams. Gauging ability band is made easier now that national statistics on 
examination pass rates are published annually 
in the UK
Gauge IQ from occupational 
recordAgain this is reasonable as a broad 
approximation, but cultural and sociological 
constraints on choice of work or progress in 
work have to be taken into account
Tests of overlearned skills

Tests of overlearned skills 
such as readingReading ability is highly correlated with IQ, and 
is a very overlearned skill, not easily affected by 
brain injury. This is the best and safest method, 
as long as the patient had no history of dyslexia and is not currently dysphasic. Tests include 
the Wechsler Test of Adult Reading
(42) and the 
Spot the Word Test(11)
Genetic endowment If the patient was damaged at birth, or if the 
damage caused gross physical deﬁ  cits adversely 
affecting educational and occupational 
potential, then the ability and educational and occupational record of natural parents and 
siblings may be considered

91
criteria are met. First, they must have an objective deﬁ  cit likely to 
impair problem-solving and decision-making. Second, they must be incapable of sensibly delegating or of appropriately seeking advice. Cognitive assessment obviously bears upon both of these issues. In the ﬁ  rst instance assessment can help gauge whether 
there is a deﬁ  cit at all, and if so its severity and precise nature. For 
example, most people would be able to manage their own lives despite some mild reduction in intellectual efﬁ  ciency or some 
mild memory problem—after all, this is in any case the course of natural ageing but it is much more difﬁ  cult to cope with a severe 
memory deﬁ  cit. In the second instance, cognitive assessment can 
point to deﬁ  cits which make it unlikely that the person can appro-

priately delegate certain responsibilities. For example, those with dysexecutive syndrome may be gullible or impulsive over whom to approach for advice, or may be reluctant to accept advice, may del-egate only inconsistently, or may say they accept certain advice but then do the opposite. In short, they cannot plan to delegate, or if they do make such plans, the plans are poorly monitored and inconsistently implemented.
Malingering
There is no single test of malingering (i.e. consciously motivated deliberate underperformance on tests). Rather, a pattern builds up which gradually raises the suspicion of malingering.
(2) Features of 
test performance which raise the issue are as follows:
 1 a degree of deﬁ  cit that is disproportionate to the severity 
of the injury;
 2 bizarre errors not typically seen in patients with genuine 
deﬁ cits;

1 a degree of deﬁ  cit that is disproportionate to the severity 
deﬁ cits;
 3 patterns of test performance that do not make sense;
 4 not showing expected patterns;
 5 inconsistencies between test performance and behaviour in real 
life;
 6 inexplicable claims of remote memory loss even for 
important life events like weddings;
 7 random responding on forced-choice tests; 8 below random responding on forced-driven tests; 9 poor performance on effort tests that look hard but are in 
fact easy;
10 the absence of severe anxiety or profoundly low mood such as 
might cause a collapse in performance;
11 after head injury, the absence of any improvement or indeed a 
worsening of performance over time;
12 failure to report deﬁ  cits following a brain injury when in 
retrospect those deﬁ  cits are claimed to have been severe;
13 relative absence of a history of somatization or related 
disorders.

Typical clinical neuropsychological assessment
Having set out the theory, tests, and issues, we can build up a picture of a typical clinical neuropsychological assessment, as given in Table 1.8.3.10.Table 1.8.3.10 Typical protocol for a clinical neuropsychological 
assessment and report
Aims The purpose of the assessment, e.g. to describe deﬁ  cits. 
monitor improvement, inform rehabilitation planning, 
address certain speciﬁ  c issues
Background of 
patientInformation relevant to the interpretation of test 
ﬁ  ndings, e.g. language, handedness, age, educational 
history, occupational history, medical and psychiatric history
Nature of the 
brain injuryFor example, time since injury, age at injury, mechanisms 
of injury, retrograde amnesia, loss of consciousness,

of injury, retrograde amnesia, loss of consciousness, 
post-traumatic amnesia, results of neurological examination, results of scans
Behaviour and 
mental stateMotivation, co-operation with procedures, anxiety, 
mood, any aspect that threatens reliability or validity, a 
clear statement as to whether or not reliability has been compromised
Intelligence Verbal, non-verbal, skills proﬁ  leSpeed Verbal, non-verbal, motorAttention and 
concentrationVerbal/spatial tasks
General behaviour and lapses on tests
Memory Verbal/non-verbal
Immediate/delayed recallLearning
Language Reading
Screening tests for dysphasia
Aphasia battery if needed
Construction 
skillsRefer to performance subtests
Copying a complex ﬁ  gure
Sensory deﬁ  cits Note gross deﬁ  cits and subjective account
Record problems noted on testsRefer to neurological examination
Tests of spatial neglect
Tests of visual agnosia

Motor deﬁ  cits Note gross problems and subjective accounts
Record problems noted on tests
Refer to neurological examination
Tests of apraxia
Executive
functionsFluency
Planning
Estimation
Personality/behaviourRecord dysexecutive problems noted on other tests
Life situation Way of life, typical day, leisure activities
Nature and amount of any support
Impact of deﬁ  cits upon everyday living
Interview with 
other informantAn observer’s account of deﬁ  cits, changes, coping, etc.
Formulation A coherent account of the injury and its repercussions, 
taking all information into account, focusing on the aims of the assessment1.8.3 cognitive assessment

SECTION 1  the subject matter of and approach to psychiatry 92
Generalizability theory and 
ecological validity
There is a broad issue how to generalize from an observation made 
in one context to what might be observed in other contexts. Traditional divisions between reliability and validity become blurred because they are both expressions of the degree to which a score can be generalized. This sweeps away the notion of a true score, to be replaced by the notion of a universe score, which is the mean of all possible observations under all possible conditions. Classical test theory is replaced by generalizability theory, in which variance in a test score is apportioned to various factors. However, in practice generalizability theory informs test construction rather than replacing classical test theory.
(15)
There is one very important aspect of generalizability, and this

(15)
There is one very important aspect of generalizability, and this 
is ecological validity or the degree to which a test score predicts real-life functioning. Some of the various threats to ecological validity are listed in Table 1.8.3.11 (see Long
(43) for a fuller discus-
sion), but the recent trend is to make neuropsychological tests increasingly a distillation of real-life tasks so as to lessen this gener-alizability problem.
(12,16,29)Cognitive assessment of psychiatric 
disorders
It is possible to give only a summary of ﬁ  ndings from the cognitive 
assessment of psychiatric and neuropsychiatric disorders. A fuller account is given by Grant and Adams
(44) and McCaffrey.(45)
Epilepsy

Epilepsy
There is no single cognitive proﬁ  le of people with epilepsy. The relationship between epilepsy and the presence of mental retardation (learning disability) will mainly be mediated by the original brain damage causing both the epilepsy and the mental retardation. However, some patients do deteriorate intellectually if seizures are frequent or uncontrolled or if there are lapses into status epilepticus. In terms of partial seizures, the most common pattern is disturbance of verbal memory if there is a left temporal (dominant) focus and of non-verbal memory if there is a right focus. Anticonvulsants themselves may mildly impair perfor-mance on a wide variety of intellectual, cognitive, and speeded tasks.
Parkinsonism
The pattern of deﬁ  cits in patients without overt dementia is mem-
ory disturbance and dysexecutive syndrome (e.g. reduced ﬂ  uency,

ory disturbance and dysexecutive syndrome (e.g. reduced ﬂ  uency, 
concept formation, ability to shift set). If there is an overt (subcor-tical) dementia, aphasia, agnosia, and severe amnesia are relatively uncommon, but mood change is frequent.
Dementia
The most common early sign of Alzheimer’s disease is poor perfor-mance on delayed verbal memory, possibly with dysexecutive signs, eventually joined by a deterioration in the meaningfulness of speech with a breakdown in semantic relationships and under-standing; speech becomes empty of content and frontal dysexecu-tive deﬁ  cits emerge.
Depression
In younger neurologically intact persons, depression affects 
attention and memory. After head injury, the presence of anxiety or depression can make a signiﬁ  cant to test scores, including IQ, 
mental speed, and verbal and spatial memory.
Alcohol

Alcohol
There is a typical neurocognitive proﬁ  le found in chronic detoxiﬁ  ed 
alcoholics after 2 to 4 weeks abstinence: intact IQ and verbal skills, but impairment of novel problem-solving, abstract reasoning, learning and memory, visual spatial analysis, and complex percep-tual–motor integration. If severe thiamine deficiency arises, Wernicke–Korsakoff syndrome may ensue, with profound antero-grade amnesia.
Other drugs(37)
Findings regarding the long-term neuropsychological effects of marijuana are equivocal, but if there are long-term changes they probably involve attention. Long-term cocaine use may also affect attention and memory. There are conﬂ  icting reports about the

long-term use of opiates, but there may be a diffuse effect upon visuospatial and visuomotor activities. Chronic solvent abuse Table 1.8.3.11  Threats to the ecological validity of test results
The assessment 
sessionData are collected in a quiet sterile focused environment, 
whereas real life is noisy and full of distractions
Type of test Cognitive tests are often constructed to measure a single 
pure aspect of processing, whereas real-life tasks are 
multidimensional
Type of 
interactionThe behaviour of the patient is constrained by the 
nature of the examiner-patient relationship, and is unlike 
spontaneous behaviour
Content of 
testsThe limited number and content of tests that can 
be given may not tap the real-life problems that are complained of (e.g. reduced sense of humour)
Confounding 
factorsTest anxiety
Motivation to co-operate with the assessment or to 
perform in a certain way
Short test sessions to avoid fatigue whereas most

Short test sessions to avoid fatigue whereas most 
problems are reported when the patient is fatigued
Over-reliance 
on test dataBlinkered adherence to numbers to the exclusion of 
background information, general observation, information 
from others, and common sense
Failure to 
consider ecological 
validityLack of understanding of the issue
Failure to follow up patients in such a way as to obtain feedback on the ecological validity of the original 
assessment, which is necessary to shape ecologically valid 
assessment procedures
Solutions Use tests of concentration and distraction
Develop new tests or new versions of tests reﬂ  ecting 
real-life tasks
Find sources of information about real-life behaviourContinue to widen the range of tests available, focusing 
test development on clinical need
Estimate effects of confounding factors
Treat numbers as only one form of data

Speciﬁ  cally address ecological issues in the ﬁ  nal report

93
leads to cerebellar ataxia and also some impairment of IQ and 
memory.
Schizophrenia
There is a growing awareness of dysexecutive deﬁ  cits in the aetiol-
ogy of schizophrenic symptoms, relating to disorders of willed action for example. Patients with schizophrenia score poorly on the Behavioural Assessment of the Dysexecutive Syndrome and show other dysexecutive features.
Summary, conclusion, and future directions
Psychometric methods based on classical test theory have permit-ted the development of reliable and valid tests assessing a wide range of intellectual and cognitive functions. T est results assist in formulation and diagnosis, guide rehabilitation and management, provide baseline measures to detect change, and generally assist clinical decision-making regarding such issues as capacity. T ests and assessment procedures are being further developed so as to improve their ecological validity, enabling better prediction of real-life behaviour and functioning.

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SECTION 1  the subject matter of and approach to psychiatry 94
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1.8.4 Questionnaire, 
rating, and behavioural methods of assessment
The earliest forms of psychiatric assessment were based on direct

The earliest forms of psychiatric assessment were based on direct 
interviews with patients, on reported observations by those who knew the patient, and on direct observations by attendants—later nurses—in the care setting. Attempts to codify these forms of assessment had begun over 90 years ago, as illustrated by the ‘Behavior Chart’ of Kempf.
(1) The present range of structured psy-

chiatric assessment methods grew from the 1950s in association with the introduction of neuroleptic medication and the develop-ment of psychiatric rehabilitation programmes. The two most fre-quently used types of systematic and structured assessment used in both clinical practice and research continue to be questionnaires and ratings. Their value lies in the systematic coverage of relevant content, and the potential for comparing scores across individuals and groups and over time.
This section covers assessment methods that are appropriate for 
both self-report by patients and others—questionnaires—and 
observations and judgements made by others about the patient 
and their immediate circumstances—rating methods. This section will also brieﬂ  y describe behavioural approaches to assessment of 
clinical relevance.
Questionnaires offer the respondent a preset range of written

Questionnaires offer the respondent a preset range of written 
questions covering the area of clinical interest, such as depression. The questions are usually completed by marking one of a set of provided response categories ( forced-choice  questions), but may 
be completed by the patient writing their own response in free text. Self-report  and ‘self-monitoring’ methods are similar to the latter 
form of questionnaire, in that the patient completes a diary or pre-marked sheets. These are more open-ended, and any associated thoughts of the patient may be included. Self-report measures are used widely in cognitive behavioural interventions.
Ratings are judgements about the quality or characteristics of
 a deﬁ  ned attribute or behaviour, completed subjectively, or on

 a deﬁ  ned attribute or behaviour, completed subjectively, or on 
the basis of direct observation of the behaviour in question. While questionnaires are usually self-completed, ratings may be completed by one person with respect to another person. In psy-chiatric practice, ratings include those made by professional staff, often a nurse or care worker, or by a family member or informal carer, about a patient.
Ratings and behavioural measures have a special use in the 
assessment of disturbed or bizarre behaviour, where the patient may have little insight or knowledge of the nature or degree of their disturbance, which may pose a major ongoing management prob-lem, or a barrier to their placement in the community. An example of such a measure is the Aberrant Behavior Checklist.
(2) This is a 
58-item behavioural rating scale completed by an informant, with the content covering ﬁ  ve subscales: irritability, agitation, and

58-item behavioural rating scale completed by an informant, with the content covering ﬁ  ve subscales: irritability, agitation, and 
crying; social withdrawal and lethargy; stereotyped behaviour; hyperactivity and non-compliance; and inappropriate speech.
The purpose of questionnaire, rating, and 
behavioural assessments
Scales may be used for a number of purposes:
◆ for the initial assessment of a patient as part of a clinical 
formulation
◆ for ongoing monitoring during the course of treatment
◆ as outcome measures
◆ for assigning patients from a larger population to a particular 
therapeutic regime
◆ for service planning
Normally an assessment will focus on the presented or referred

Normally an assessment will focus on the presented or referred 
patient. However, it may be helpful to either focus on a family member or on a formal or informal direct carer of the patient. Another potential focus is the patient’s environment. The range of behaviour a patient can display is limited by the physical nature of their environment, by the range of equipment or materials avail-able to the patient, and by the social rules of the setting (such as rules against smoking). A rating of environmental restrictiveness would then survey both environmental constraints and the range of formal institutional regulations and informal rules followed by care staff.
Most measures simply describe the current functioning of the

Most measures simply describe the current functioning of the 
patient, without offering a framework for translating the obtained scores into clinical priorities for treatment. An important development in rating methodology has been the ‘needs assessment’ approach that incorporates the views of patients and carers when taking into account the extent to which their needs have been met, or remain unmet. The Camberwell Assessment of Need (CAN) family of measures
(3) has adopted a consistent set of content domains, which 
has been applied to separate need assessment schedules which can now be applied to adults, older adults, people with learning dis-abilities, and in forensic settings.

95
Scale content
A questionnaire or rating is deﬁ  ned by both overall content  and 
item format . The content of a measure should logically be deter-
mined by its purpose. One model of assessment(4) suggests that 
there are four main content areas for assessment, including cogni-tion, affect (including verbal-subjective components of behaviour), physiological activity, and overt behaviour. The content should cover all the domains of clinical relevance, including current and past behaviour, and psychopathology. While most rating scales cover a relatively limited number of functional areas, and are often designed for use with a speciﬁ  c client group or clinical population, 
some measures are designed for wider use.
The format of each item typically consists of an item stem , or 
question, followed by a set of response options . The item stem and

question, followed by a set of response options . The item stem and 
responses should be grammatically complementary, and the total set of response options for each item should together cover all logi-cally possible response options. Responses should use exact fre-quencies (such as ‘twice a day’ or ‘at least every hour’) rather than vague terms such as ‘often’ or ‘frequently’ . Response options may be set out verbally, or may have a numerical value attached. Usually the responses for each item will be laid out in sequence to form a graded series of increasing or decreasing severity or quality of response. These items may be set out in unipolar (where one end is 
‘zero’ or nil occurrence) or bipolar  (with the mid-point being neu-
tral or ‘normal’) form. In general, if an item has more than ﬁ  ve

tral or ‘normal’) form. In general, if an item has more than ﬁ  ve 
response options there is a risk of poor reliability. Figure 1.8.4.1 illustrates the most common individual item formats.
Most items in questionnaires and rating scales are designed to 
produce ordinal scores—that is, the score simply gives the relative order of items, without implying any mathematical equality of the differences between scores. This limits the statistical methods that can be used with the scores arising from these measures.
Criteria for evaluating questionnaires and 
rating scales
There are a number of technical and practical factors to bear 
in mind in appraising and selecting a measure. Anyone using a published questionnaire or rating scale should examine the techni-

cal qualities of the measure, which should be included in the origi-nal publication or on a scale manual. This is both to critically assess whether or not a speciﬁ  c measure is suitable for the intended pur-
pose, and also to understand how best to use the scale in practice—including any training requirements.
Psychometric adequacy
Psychometric criteria are the most important technical ways to evaluate the quality of a measure. Chapter 1.8.3 outlines those minimum psychometric principles and properties that are applicable to all psychological measures, including the classical approaches to scaling, reliability, validity, and sensitivity to change, 
as well as generalizability approaches. The most widely known psy-

chometric requirements of any scale are validity and reliability: neither of these are inherent properties of a scale. Scales are valid for speciﬁ  c purposes, which should be clearly described in the 
original published article about a scale.
The form of reliability most characteristic of rating scales, and 
of other behavioural measures, is inter-rater or inter-observer reli-ability, which examines the similarity of scores when two or more different raters administer a scale. Ideally the manual for a scale should describe a rater training procedure. If not, it is always sensible to carry out some basic rater training, carrying out some assessments prior to the main study, analyzing score discrepancies, and ensuring that raters have discussed these differences and why 
they arose.
Typically, ratings may be completed after an observation period

Typically, ratings may be completed after an observation period 
varying from a few minutes or hours, to a few days. For those ratings based on observation periods of more than a day, there is then a variable delay between the relevant observations and the completion of the rating, and also any one observer will only have been present or on duty for a proportion of the observation period. Unless the observer against whom reliability is being assessed is observing for exactly the same period, the periods of observation will not be coincident. Under these circumstances a double rating may not be strictly a reliability check, but more of a check of the stability of the behaviour. Patel et al .
(5) discuss how the use of a 
simple checklist of the occurrence of key events can substantially improve the reliability of this type of scale.
A further technical issue for observer-based scales is that of reac-

tivity, which is the change in behaviour due to the patient’s aware-ness of the presence of an observer. Any live observer will induce 
some reactivity effects, and this issue is often ignored. Reactivity factors may be reduced by making the observation procedure as minimally intrusive as possible by, for example, careful siting of the observer.
Practical factors and an example
Because of their apparent simplicity, the limitations of question-naires are not always considered. Bowling
(6) has reviewed the 
main sources of variation in data quality between four modes of administering questionnaires, comparing face-to-face inter-views, telephone interviews, self-administration, and electronic procedures. The quality of data was deﬁ  ned in terms of overall

response rates, item response rates, response accuracy, and social desirability response bias. These different ways of administering questionnaires have differing cognitive demands on respondents, 
Fig. 1.8.4.1 Examples of item formats .Direct frequency count
How many cigarettes a day do you smoke? ....Dichotomous or binary item  (used in checklists)
Have you ever smoked a cigarette?          Y es               NoThree or more response optionsa. Nominal scaling:  please describe your marital status
Single       Married       Separated/divorced       Widowedb. Ordinal Unipolar:  how often do you feel constipated?
Never     Between 1 and 3 times a week     4 or more times a weekc. Ordinal Bipolar:  how good are you as a car driver?
Above average       average       below averageLinear  or Visual analogue  scale (the line is usually 10 cm long)
What quality of care have you received?
Very poor Very good1.8.4 questionnaire, rating, and behavioural methods of assessment

SECTION 1  the subject matter of and approach to psychiatry 96
so that face-to-face interviews tend to yield higher quality 
data. Regier et al.(7) point out the need to standardize measures for 
both clinical and epidemiological work, given the ‘drift’ or ‘muta-tions’ that can occur with repeated use of even the most carefully designed measures, with major consequences, for example, for public health and policy if prevalence estimates cannot be made reliably.
Practically, scales should be written at the level of vocabulary

Practically, scales should be written at the level of vocabulary 
simple enough for the lowest level of educational attainment likely to be found among scale users. Usually one type of item format is used throughout the scale: sometimes the wish to have one format means that some items are then not easy to understand because that one format is not suited to the content of every item. Shorter scales are usually preferred to longer ones. Some scales are in the public domain. Others are copyright and payments should then be made each time a copy of the scale is used.
There are several steps involved in creating a questionnaire or 
rating scale. The creation of the original item pool is the ﬁ  rst step in designing a new measure, and often existing measures provide some of the items, as well as those identiﬁ  ed from any

rating scale. The creation of the original item pool is the ﬁ  rst step in designing a new measure, and often existing measures provide some of the items, as well as those identiﬁ  ed from any 
other surveys or studies. Individual items must be selected from this pool, implying, making judgements about the most impor-tant topics to cover, and about the bandwidth of the possible range of response options from ‘normal’ to the most extreme likely to be found.
McGuire et al.
(8) give a very clear description of the construction 
of a new rating scale to assess the quality of the clinician–patient therapeutic relationship in community care. They describe the four stages in the creation of the scale:
◆ generating an item pool
• conducting semi-structured interviews with clinicians and 
patients
• reviewing the content of existing scales covering the same 
phenomena
◆ identifying factors and items in the new scale
• original pool of items rated by clinicians and patients

patients
phenomena
• rating scores subjected to principal components factor 
analysis
◆ conducting a test–retest reliability study of the new scale
◆ testing the factorial structure of the revised new scale in a new 
sample of clinicians and patients
Multiple measures
In both clinical practice and research, the concurrent use of several different measures may be helpful, addressing different categories of functioning and behaviour, with care taken to consider the overall assessment load on any one staff member in the light of their other clinical commitments. Rutter,
(9) in reviewing changes

(9) in reviewing changes 
in child psychiatry, pays particular attention to the importance of sound measurement by contrasting standardized interviews and checklists, and points out that multiple measures involving dif-ferent informants, which are repeated over time, are necessary to reduce error and minimize rater bias. Self-completed question-naires may supplement observer-completed ratings or checklists in the assessment of speciﬁ  c behavioural problems. Deale et al.
(10)
in evaluating the outcome of a treatment trial for chronic fatigue, 
used 10 outcome measures, namely: three functional impairment measures; two fatigue measures; two psychological distress questionnaires or inventories; and three other variables, including a global self-rating and a self-written statement of illness attributions.
Behavioural and observational 
assessment methods
A number of existing simple observational methods were reﬁ  ned

A number of existing simple observational methods were reﬁ  ned 
alongside the clinical introduction of behaviour therapy procedures in the 1960s, and these continue to be associated with contempo-rary cognitive behavioural interventions (see Fig. 1.8.4.2).
These methods focus on current overt behaviour, and are used 
for the immediate recording of events, for example counting the number of times an event occurs (leading to frequency counts), or coding observed event by using a set of prescribed behavioural categories that exhaustively and mutually exclusively cover all anticipated possibilities. Direct observation methods can be used in a standardized manner for a group of patients. But they also lend themselves to ﬂ  exible modiﬁ  cation, so that the frequency and the 
duration of observation periods, and coding systems, can be chosen to suit the requirements of the behavioural difﬁ  culties of an 
individual.
Functional analysis

The term ‘functional analysis’ generally refers to attempts to dis-
cern the variables controlling or maintaining a phenomenon. It usually describes the observation of an individual’s behaviour of clinical signiﬁ  cance, linked to the observation of those events in the 
immediate environment that directly preceded, were concurrently associated with, and followed, the target behaviour. This sequence of antecedent environmental events, target behaviour  and concur-
rent events, and consequent  environmental events, is often called 
anABC  analysis. For example, incidents of aggression by a particu-
lar client in a day-setting may be a function of who is near them or talking to them, so that a record of their presence or absence would be important.
Sampling

Sampling
A key issue with both rating and direct observational methods is the spread of observation periods over the waking day. Since many behaviours vary in their natural frequency during the waking day, many events should, theoretically, be observed continuously throughout the day. However, since the time needed for continual observation is usually unavailable, a representative sample of the whole day should be observed. Ideally, a random sample of time 
Fig. 1.8.4.2. Categories of behavioural and observational assessment methods.Functional analysis
Event samplingTime samplingResponse codingSelf-report and self-monitoring methodsPsychophysiological methods

97
periods throughout the day should be observed. When events of 
clinical interest are very complex, it may take too long to code each event fully, so then only, say, every ﬁ  fth or tenth event is coded in 
detail—this is termed as event sampling . When events are happen-
ing very rapidly, or if they tend to happen at about the same rate during the day, it is time-wasting to observe all the time, so obser-vations may then be made only every 15 or 30 min—this is termed astime sampling .
Response coding
A set of qualitative coding categories should cover all the most likely 
events, using clear and unambiguous language, coding categories should be simple enough to be entered quickly. When continuous observation is used, especially for high rates of behaviour, the observer must be allowed regular rest periods.
Psychophysiological methods

These methods typically involve the use of surface sensors to mea-sure changes in, for example, skin electrical conductivity (as in mea-suring changes in sweating), in light transmission (as in measuring changes in ﬁ  nger blood ﬂ  ow), and in volume (as in plethysmogra-
phy). These sensors are now always electronic, so the electrical sig-nals from them are calibrated with the associated physical change, which is taken as a proxy measure for the assumed underlying change in physiological arousal. The small size, low weight, and the sophisti-cation and reliability of electronic recording equipment, including hand-held electronic event recorders, now allows the immediate and unobtrusive recording of events, with concurrent data analysis.
Standard or individualized measures?
There are many standard ratings and questionnaires already in 
existence covering most areas of clinical interest. However, the fact

existence covering most areas of clinical interest. However, the fact 
that a scale is well used does not necessarily mean that it is psycho-
metrically sound, or that the content covered is appropriate for a 
given clinical or research purpose. Rating scales may continue to be used widely when they are no longer the best scales technically, but 
because the volume of published research in which they have been used permits comparisons with other studies.
Solutions to this dilemma are either to create a totally new mea-
sure, making sure it is better than its predecessor, or to improve 
systematically the properties of an existing measure. Parker et al .
(11) describe a modiﬁ  cation of the well-established parental

(11) describe a modiﬁ  cation of the well-established parental 
bonding instrument to include abusive parenting, which was omitted in the original version. Their article demonstrates both how to modify an original measure to improve item wording, and at the same time incorporate additional material to increase the value of the measure. An unsound solution is to change the mea-sure in an ad hoc  way—scale vandalization!—with no awareness 
of the principles of sound scale and item construction. This only results in an instrument that will then be of poor or unknown reli-ability or validity.
The value of rating and questionnaire methods is that they can be used by a variety of assessors who do not need to be qualiﬁ  ed mental 
health professionals—although the need for at least some training in rating methods should not be overlooked. They can be presented in

health professionals—although the need for at least some training in rating methods should not be overlooked. They can be presented in 
very short versions therefore making minimal demands on both assessors and patients, and so can lead to high levels of compliance. Since they can be used by patients, they can themselves be tools to increase engagement and to give patients direct feedback about their own current state. Behavioural and observational assessment mea-sures constitute a clinically useful subgroup of methods, which potentially have high validity with respect to day-to-day functioning. However, the apparent simplicity of all of these methods masks the need for care in their construction, the importance of training in their use, and caution in over-sophisticated interpretation of data arising from their use.
There are a number of helpful core  texts, describ ing general technical 
issues in questionnaire and rating scale design (see Streiner & Norman

(a) and McDowell(b)). Similarly Haynes & O’Brien(c) and 
Hersen(d) cover the general principles of behavioural assessment. 
Andrews et al.(e) give an excellent review of outcome measures in 
mental health, covering many of the most commonly used rating scales. McDowell
(b) and Bowling(f) include extensive lists of the 
most commonly used scales in health and social care, including those covering mental health issues.
(a) Streiner, D.L. and Norman, G.R. (2003). Health measurement scales .
(b) McDowell, I. (2006). Measuring health: a guide to rating scales and 
questionnaires . Oxford University Press, Oxford.
(c) Haynes, S.N. & O’Brien, W.H. (2000). Principles and practice of 
behavioural assessment . Springer, New Y ork.

(d) Hersen, M. (2005). Clinician’s handbook of adult behavioral assessment .
Academic Press, New Y ork.
(e) Andrews, G., Peters, L., and T eesson, M. (1994). The measurement of 
consumer outcome in mental health: a report to the National Mental Health Information Strategy Committee . Clinical Research Unit for 
Anxiety Disorder, Sydney, Australia.
(f) Bowling, A. (2004). Measuring health . Open University Press, 
Maidenhead.
 1. Kempf, E.J. (1915). The behavior chart in mental diseases. American 
Journal of Insanity ,71, 761–72.
 2. Aman, M.G., Singh, N.N., and Stewart, A.W. (1985). The aberrant 
behavior checklist: a behavior rating scale for the assessment of treatment effects. American Journal of Mental Deﬁ  ciency ,89,
485–91.

485–91.
 3. See www.iop.kcl.ac.uk/hsr/prism/can 4. Eifert, G.H. and Wilson, P .H. (1991). The triple response approach to 
assessment: a conceptual and methodological reappraisal. Behaviour 
Research and Therapy ,29, 283–92.
 5. Patel, V ., Hope, T., Hall, J.N., et al.  (1995). Three methodological 
issues in the development of observer-rated behaviour rating scales: 
experience from the development of the rating scale for aggressive 
behaviour in the elderly. International Journal of Methods in Psychiatric 
Research ,5, 21–7.
 6. Bowling, A. (2005). Mode of questionnaire administration can have 
serious effects on data quality. Journal of Public Health ,27,
281–91.1.8.4 questionnaire, rating, and behavioural methods of assessment

SECTION 1  the subject matter of and approach to psychiatry 98
 7. Regier, D.A., Kaelber, C.T., Rae, D.S., et al. (1998). Limitations of 
diagnostic criteria and assessment instruments for mental disorders. Archives of General Psychiatry ,55, 109–15.
 8. McGuire-Snieckus, R., McCabe, R., Catty, R., et al.  (2007). A new scale 
to assess the therapeutic relationship in community mental health care: STAR. Psychological Medicine ,37, 85–95.
 9. Rutter, M. (1997). Child psychiatric disorder: measures, causal 
mechanisms, and interventions. Archives of General Psychiatry ,54, 785–9.10. Deale, A., Chalder, T., Marks, I., et al.  (1997). Cognitive behaviour 
therapy for chronic fatigue syndrome: a randomized controlled trial. American Journal of Psychiatry ,154, 408–14.
11. Parker, G., Roussos, J., Hadzi-Pavlovic, D., et al.  (1997). The 
development of a reﬁ  ned measure of 
dysfunctional parenting

dysfunctional parenting 
and assessment of its relevance in patients with affective disorders. Psychological Medicine, 27,
1193–203.

1.9
Diagnosis and classiﬁ  cation
Michael B. First, and Harold Alan Pincus
In Psychiatry, as in all of medicine, diagnosis is a key function and 
central to developing a plan of treatment for patients. Psychiatry, however, faces special challenges. The etiopathogenesis of most psychiatric disorders is not known. For the most part, a clinician must rely on reports from, and direct observation of patients to gather the necessary information to determine a diagnosis. Until very recently, laboratory tests had little relevance. Even diagnostic information found in medical records may not be useful, since the clinician cannot ascertain whether the historically recorded diag-noses of previous clinicians were based on reliable observations, the application of similar diagnostic approaches, or even the same system of classiﬁ  cation. These special challenges faced by the ﬁ  eld 
have ensured that diagnosis and classiﬁ  cation in psychiatry has a 
long and rich history.
Deﬁ nitions

The term ‘diagnosis’ can mean both the name of a particular 
disease as well as the process of determining or ‘making’ a diagnosis. In medicine, generally, various terms are used to describe a patho-logical entity. When there is the presence of objective pathology or the presumed understanding of aetiology, the term ‘disease’ is gen-erally used, e.g., pancreatic cancer, strep throat, Alzheimer’s disease. In instances of unknown aetiology or when the disease process is not apparent, the term ‘disorder ’ is usually applied with a syndromic 
characterization, i.e., deﬁ  nition based on symptom presentation, 
history, and sometimes, associated laboratory ﬁ  ndings. Other terms

history, and sometimes, associated laboratory ﬁ  ndings. Other terms 
are also used in common parlance, such as ‘illness’ for an individual’s subjective awareness of distress and ‘sickness’ for the inability to perform usual social roles. For the most part, in psychiatry, the term ‘disorder’ is used.
Classification represents the process of placing diagnostic 
entities into various groupings in a systematic way, based on a set of principles with regard to the similarities and differences among these categories. Depending upon the principles and conceptual framework underlying the categorization process, classiﬁ  cations 
can be very different.
Goals of the classiﬁ  cation
In some ways, the most important question may be ‘whose needs 
is the classiﬁ  cation primarily intended to address?’ Clinicians want

is the classiﬁ  cation primarily intended to address?’ Clinicians want 
a classiﬁ  cation that can categorize as many people that come in for help as possible. They want the classiﬁ  cation to facilitate the identi-
ﬁ cation and treatment of patients and provide guidance on prog-
nosis and cause. Researchers want to have groupings that are highly 
homogeneous in order to test the efﬁ  cacy of speciﬁ  c treatments and 
to better understand the aetiology of speciﬁ  c disorders. Educators 
want a classiﬁ  cation system to offer a structure for teaching about

want a classiﬁ  cation system to offer a structure for teaching about 
psychopathology and differential diagnosis. Public health adminis-trators want to track epidemiology, health utilization, and costs over time. Some argue that psychiatric diagnosis is a reductionistic labelling of individual differences or social deviance and exposes individuals to potential stigma. At a minimum, they would like a psychiatric diagnostic system to be less prone to misuse. Ultimately, most classiﬁ  cations attempt to balance among those competing 
priorities, not always successfully. In some cases, e.g., the ICD-10, different products are developed for different target groups, i.e., research diagnostic criteria for investigators, a simpler, more aggregated classiﬁ  cation for primary care providers, etc.
Conceptual issues
A range of conceptual issues and their resolution determines the

A range of conceptual issues and their resolution determines the 
principles and rules governing a system of classiﬁ  cation. It is 
important to note, however, that classiﬁ  cation systems do not 
necessarily apply these rules in a consistent manner. Some of the issues noted below may not be resolved in an absolute manner, but in a way that employs compromises among multiple priorities, e.g. balancing the needs of clinicians, researchers, educators, and public health administrators or having some diagnostic groupings based on a descriptive approach and others on a theory-based approach.
Descriptive v. theory-based:  Do the classiﬁ  cation principles emanate 
from a theory regarding the aetiology or mechanisms of psychopa-thology (e.g. psychodynamics, behavioural, neurobiological) or does the classiﬁ  cation attempt to provide a theoretical heuristic 
framework for describing syndromic entities?
 Pathology v. normalcy:  What assumptions underlie distinguish-

ing what constitutes a ‘mental disorder’ or ‘caseness’ from nor-mative behavior?
 Categorical v. dimensional:  Does the classification assume 
discrete categories with sharp boundaries or does it assume that psychopathology lies on a continuum across a range of dimen-sions (and if so, what dimensions and how were they chosen?)

SECTION 1  the subject matter of and approach to psychiatry 100
 Lumping v. splitting:  Does the classiﬁ  cations system establish a 
smaller number of broad, relatively heterogeneous categories or numerous homogeneous categories?
 Multiple v. single diagnosis:  Is there a hierarchy where certain 
diagnoses have priority and ‘trump’ other diagnoses if an individ-ual ﬁ ts into more than one category or are multiple simultaneous 
diagnoses (i.e. comorbidity) encouraged to communicate more complete diagnostic information?
The development of modern classiﬁ  cations
The first international classification of diseases in 1855 was 
concerned with a nomenclature of causes of death.(1) After many 
revisions this list was adopted by the World Health Organization (WHO) in 1948 and the so-called Sixth Revision of the International 
Statistical Classiﬁ  cation of Diseases, Injuries and Causes of Death(ICD-6) was produced.
(2) The sixth edition of the ICD included for

(2) The sixth edition of the ICD included for 
the first time a classification of mental disorders, containing 10 categories of psychoses, nine categories of psychoneurosis, and seven categories of character, behaviour, and intelligence. A num-ber of problems with this classiﬁ  cation (e.g., many important cat-
egories such as the dementias, many personality disorders, and adjustment disorders were not included) rendered it unsatisfactory for use in most countries; only ﬁ  ve countries, including the United 
Kingdom, adopted it ofﬁ  cially. The ﬁ  rst edition of the American 
Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-I)
(3) was published in the United States as 
an alternative to ICD-6. For the ﬁ  rst time in an ofﬁ  cial classiﬁ  ca-
tion, glossary deﬁ  nitions of the various disorders were included in 
addition to the names of the disorders.

Work on ICD-8 began in 1959 with the goal of developing a 
classiﬁ  cation system that would be acceptable to all of its member 
nations. The resulting system, ICD-8, went into effect in 1968, and in 1974 added a glossary which was largely based on British views about diagnostic concepts.
(4) Coincident with the develop-
ment of ICD-8, the American Psychiatric Association prepared a second edition of its DSM based on ICD-8, deﬁ  ning each disorder 
for use in the United States.
(5)
 The early 1970s saw the introduction of explicit operationalized 
diagnostic criteria that were developed for research purposes. Although the glossary deﬁ  nitions of disorders in DSM-II and

(5)
diagnostic criteria that were developed for research purposes. Although the glossary deﬁ  nitions of disorders in DSM-II and 
ICD-8 were an improvement over just having a list of diagnostic categories, these brief descriptions were too vague to be useful in identifying diagnostically homogeneous populations for study. Researchers responded to this need by developing their own opera-tionalized criteria. The ﬁ  rst set of diagnostic criteria that covered 
a wide range of disorders was developed by Robins and Guze at Washington University in St. Louis
(6) with the stated purpose of 
‘provid[ing] common ground for different research groups so that diagnostic deﬁ  nitions can be emended constructively as further 
studies are completed’ . (p. 57). They were known as the ‘Feighner criteria’ after the ﬁ  rst author of the paper that presented them.

studies are completed’ . (p. 57). They were known as the ‘Feighner criteria’ after the ﬁ  rst author of the paper that presented them. 
Criteria sets for 16 disorders were presented and listed those features required for each diagnosis (known as ‘inclusion criteria’) as well as features whose presence would rule out the disorder (known as ‘exclusion criteria’). The Feighner criteria proved to be enormously useful to the research community as illustrated by the large number of times they were cited in other papers (i.e. 1650 citations from 1972 to 1982 as compared to the typical average of 2.1 citations per paper). Several years later, an expanded set 
of research criteria based on the Feighner criteria was developed to meet the needs of a National Institute of Mental Health-sponsored collaborative project on the psychobiology of depression.
(7) These 
criteria, known as the Research Diagnostic Criteria (RDC) subse-

(7) These 
quently became very popular among researchers and were heavily used, especially in research on mood and psychotic disorders. 
 T o develop the mental disorders section for ICD-9, WHO initi-
ated an intensive program to identify problems encountered by psychiatrists in different countries in the use of the mental disor-ders section of ICD-8 and to formulate recommendations for their solution. A series of eight international seminars were held annu-ally from 1965 to 1972, each of which focussed on a recognized problem in psychiatric diagnosis. The outcome of the seminars formed the basis for the recommendations made for ICD-9,
(8)
which was ultimately published in 1978. 
As work progressed on the development of ICD-9, the American 
Psychiatric Association decided to develop a third edition of its diagnostic manual, DSM-III.
(9) This decision was made both

(9) This decision was made both 
because of identiﬁ  ed inadequacies of the ICD-9 for research and 
clinical use, and because the ICD-9 did not include important inno-vations that had already been demonstrated by researchers to be both technically feasible and useful, like operationalized diagnostic criteria. Under the leadership of Robert L. Spitzer, successive drafts of DSM-III were prepared by 14 advisory committees, with the drafts being distributed among both American and international psychiatrists for comments and review. Many of the DSM-III crite-ria sets were based on the RDC criteria, with the rest developed based on expert consensus. 
The improvement in reliability over DSM-II (which provided 
only glossary deﬁ  nitions) was demonstrated by a large NIMH-
supported ﬁ  eld trial in which clinicians were asked to indepen-

dently evaluate patients using drafts of the DSM-III criteria.
(10)
The explicit diagnostic criteria provided for each of the disorders 
in the classiﬁ  cation were based on the symptomatic presentation of

(10)
in the classiﬁ  cation were based on the symptomatic presentation of 
the disorder rather than on theories about the underlying cause. Even though the DSM-III was a product of the American Psychiatric Association, its adoption of this ‘descriptive approach’ resulted in its widespread acceptance by all mental health professionals in the United States, regardless of their theoretical orientation. For exam-ple, clinicians from different orientations might have very different understandings of what causes panic attacks; a cognitively-oriented clinician might attribute a panic attack to the person’s tendency to catastrophize in response to normal physical sensations like increased heart rate; a neurobiologically-oriented clinician might consider panic attacks to be due to overactivity of brain circuitry 
involved in ﬁ  ght-or-ﬂ  ight responses, and a psychodynamically-

oriented clinician might see panic as a consequence of the break-down of the defense organization at various levels. Despite these 
divergent hypotheses, however, all of these clinicians can agree on 
how a panic attack presents (i.e. a discrete period of apprehension or fear with at least four symptoms such as shortness of breath, palpitations, chest pain, choking, dizziness, etc), thus facilitating communication among them. 
DSM-III also introduced the use of a multiaxial system for 
recording the diagnostic evaluation. The multiaxial system facilitated the use of a biopsychosocial model of evaluation by separating (and thereby calling attention to) developmental and personality disorders (Axis II), physical conditions (Axis III), stressors (Axis IV),

101
and degree of adaptive functioning (Axis V) from the usually more 
ﬂ orid presenting diagnoses (Axis I).
Despite initial opposition among some psychiatrists (most 
especially those with a psychoanalytic orientation), DSM-III proved to be a great success, becoming the common language of mental health clinicians and researchers for communicating about mental disorders. Although it was intended primarily for use in the United States, it was translated into 13 languages and was widely used by the international research community.
Experience with DSM-III in the few years after its publication in 
1980, revealed a number of inconsistencies and lack of clarity in the diagnostic criteria sets. Furthermore, research conducted in the early 1980’s demonstrated errors in some of the assumptions that went into the construction of the DSM-III criteria sets. For exam ple,

the DSM-III prohibition against giving an additional diagnosis of Panic Disorder to individuals with both Major Depressive Disorder and panic attacks was shown to be incorrect based on data demonstrating that relatives of individuals with both Major Depressive Disorder and Panic Attacks can have either Major Depressive or Panic Disorder.
(11) For these reasons, work began on 
a revision of the DSM-III, which was published as DSM-III-R in 1987.
(12)
Initial work began on the development of the psychiatric section 
of the 10th Revision of the International Classiﬁ  cation of Diseases
(ICD-10), in 1982 under the chairmanship of Norman Sartorius. After a meeting of WHO representatives and consultants together with representatives of the American Drug and Mental Health Administration in Copenhagen in 1982, several further meetings took place (e.g. in Djakarta and in Geneva in 1984) in which a pro-visional psychiatric classiﬁ  cation was designed. It was decided that

the ICD-10 classiﬁ  cation of mental disorders would be produced 
in several versions. The ﬁ  rst of these is to be used, as are other 
parts of the International Classiﬁ  cation of Diseases, mainly for sta-
tistical purposes, and included a short glossary deﬁ  nition for each 
category.
(13) This is the version that was ofﬁ  cially approved by the 
World Health Assembly and thus, is the version for which interna-tional compatibility is mandated by treaty agreements. The second version, Clinical Descriptions and Diagnostic Guidelines is for the use of the practicing clinician.
(14) Each category in this version has 
a detailed deﬁ  nition specifying the main features of the disorder 
followed by diagnostic guidelines. The third version, the Diagnostic Criteria for Research is primarily intended for research and con-tains diagnostic criteria which are stricter in form than those in the clinical diagnostic guidelines from which they were derived.
(15) For

(15) For 
example, while the guidelines may indicate that a particular disor-der ‘usually starts in early childhood’ , the diagnostic criteria for research would specify that the diagnosis ‘should not be made if the onset is after the age of 30’ , The decision to separate the criteria for research from the clinical guidelines was made because clinicians in 
their daily work do not observe overly strict rules when making 
diagnoses, which are of cardinal importance for research.
(16)
Finally, a version of the mental disorders section was produced for use in primary care settings.
(17) It contains a much smaller number 
of categories (i.e. those that are frequently encountered in every day general practice) as well as treatment guidelines corresponding to these categories.
By 1986, a ﬁ  rst draft of the psychiatric chapter, including details

By 1986, a ﬁ  rst draft of the psychiatric chapter, including details 
of the categories, code numbers, diagnostic guidelines, and precise diagnostic criteria for research had been written, and by June 1987, the clinical diagnostic guidelines were being circulated by WHO’s 
division of mental health for ﬁ  eld trials in 194 different centers 
in 55 different countries.
(18) In 1989, the International Revision 
Conference, attended by representatives of the health ministries 
of a majority of WHO member states gave formal approval to the basic categories and text. A draft of the diagnostic criteria for research was produced in 1990 and ﬁ  eld trials to evaluate 
inter-rater agreement, conﬁ  dence in diagnosis, and ease of use 
began later in the year.
(19) Finally, in 1990, the World Health 
Assembly formally approved its introduction in member states starting in January 1, 1993.
The American Psychiatric Association started work on the

The American Psychiatric Association started work on the 
development of DSM-IV in 1988, shortly after the publication of DSM-III-R, spurred on by the need to coordinate its development with the already ongoing development of ICD-10. DSM-IV contin-ued the descriptive atheoretical approach advanced by both DSM-III and DSM-III-R, but this time also incorporated a meta-analytic data-based revision process to guide changes.
(20,21) This 
was in contrast to both DSM-III and DSM-III-R which by necessi-ty, given the paucity of available empirical data, relied almost exclu-sively on expert consensus. The DSM-IV workgroups began their deliberations by identifying a series of diagnostic questions to be considered and problems to be addressed and employed a three-stage empirical review process to address, these questions. The ﬁ  rst

stage involved a systematic comprehensive review of the published literature guided by literature searches using rules established at a DSM-IV methods conference. The second stage involved supple-menting the literature reviews with a data reanalysis project funded by the MacArthur foundation in which existing data sets collected for other studies were combined and analyzed using meta-analytic methods. These data reanalyses were useful in answering a number of diagnostic questions (e.g. determining the minimum number 
of panic attacks required in order to justify a diagnosis of panic 
disorder) but were unfortunately limited by incompatibilities in the data sets and the fact that the data needed to answer speciﬁ  c 
diagnostic questions often had not been collected. Proposed criteria sets formulated based on the literature reviews and data reanalyses were then tested in 15 NIMH-funded multi-site ﬁ  eld trials. The

entire empirical review process and the reasons underlying the decisions made by the DSM-IV workgroups have been document-ed in the four volume DSM-IV Sourcebook.
(22–25)
In order to increase compatibility between ICD-10 and DSM-IV , 
a collaborative relationship was established between the DSM-IV workgroups and the developers of ICD-10. Two meetings were convened in which the respective workgroups joined forces with the goal of minimizing the differences between diagnostic deﬁ  ni-
tions in the two systems. Unfortunately, the potential to make the two systems identical was seriously constrained by differences in the timelines between the two revision processes. By the time the 
DSM-IV workgroups were ﬁ  rst convened in 1989, the categories 
and basic text of the ICD-10 had already been settled by the International Revision Conference.
(26) Thus, although final

(26) Thus, although final 
DSM-IV and ICD-10 systems were much more similar than were DSM-III and ICD-9, a number of mostly small differences in crite-ria sets persist. While some of the discrepancies are the result of genuine differences in diagnostic outlook (e.g., the one month duration of ICD-10 schizophrenia vs. 6 month duration of DSM-IV schizophrenia), the overwhelming majority appear not to have any justiﬁ  cation.
(27)1.9 diagnosis and classification

SECTION 1  the subject matter of and approach to psychiatry 102
One of the most important uses of the DSM-IV has been as an 
educational tool. This is especially true of the descriptive text that accompanies the criteria sets for the DSM-IV disorders. Given that the interval between DSM-IV and DSM-V was being extended from seven years between DSM-III and DSM-III-R, and between DSM-III-R and DSM-IV to at least 12 years, concerns were raised that the information in the text would become increasingly out-of-date over time. Therefore, in order to bridge the span between DSM-IV and DSM-V , a revision of the DSM-IV text was under-taken.
(28) The primary goal of the DSM-IV-TR was to maintain the 
currency of the DSM-IV text, which reflected the empirical literature up to 1992. Thus, most of the major changes in DSM-IV-TR were conﬁ  ned to the descriptive text. Changes were made to 
a handful of criteria sets in order to correct errors identiﬁ  ed in

a handful of criteria sets in order to correct errors identiﬁ  ed in 
DSM-IV . In addition, some of the diagnostic codes were changed to reﬂ  ect updates to the ICD-9-CM coding system adopted by the 
U.S. Government.
Differences between DSM-IV and ICD-10
A fundamental difference between the ICD-10 and the DSM-IV reﬂ ects the different purposes of the two systems, i.e., that ICD-10 
is set up as a classiﬁ  cation system whereas DSM-IV is a diagnostic

is set up as a classiﬁ  cation system whereas DSM-IV is a diagnostic 
nomenclature. The primary goal of the ICD is to facilitate the col-lection of statistics about those individuals who present themselves to a health care professional. Thus, the ICD has been designed to provide the coder with an unambiguous choice of diagnostic cate-gory given a particular case. The main rule for deciding whether to include a diagnostic category in the ICD is its common interna-tional usage. Inclusion of a category in the ICD carries with it no implication of diagnostic validity—in fact, a number of categories included in ICD-10 were considered for inclusion in DSM-IV— but were not added because of concerns about their validity (e.g., mixed anxiety depression). In contrast, inclusion of a category in 
the DSM implies that the category has been ofﬁ  cially sanctioned by

the DSM implies that the category has been ofﬁ  cially sanctioned by 
the American Psychiatric Association as appropriate for clinical and research usage, i.e., the category has both clinical utility and is backed up by an empirical data base. It should be noted, however, that the empirical data base is not equivalent for all of the categories—to minimize disruption, diagnostic categories, that were included in earlier editions of the DSM have been ‘grand-fathered’ in. Starting with DSM-IV , new categories were only added if they met these higher standards.
Another important difference between the DSM and ICD 
approach is the role of impairment in the deﬁ  nition of a disorder. 
With only a few exceptions (e.g., dementia, phobias), mental disorders in ICD-10 are deﬁ  ned exclusively by the symptomatic

With only a few exceptions (e.g., dementia, phobias), mental disorders in ICD-10 are deﬁ  ned exclusively by the symptomatic 
presentations—there is no requirement that the symptoms cause any impairment in the individual’s level of functioning. Impairment in functioning caused by the symptoms is indicated in ICD-10 by using an orthogonal scale, the International Classiﬁ  cation of 
Functioning.
(29) In contrast, most of the DSM-IV criteria sets 
include a criterion (known as the ‘clinical signiﬁ  cance criterion’) 
requiring that the disturbance causes clinically signiﬁ  cant distress

requiring that the disturbance causes clinically signiﬁ  cant distress 
or impairment in social, occupational, or other important areas of functioning. According to the introduction of the DSM-IV , this criterion has been included to help establish ‘the threshold for the diagnosis of a disorder in those situations in which the symptom-atic presentation by itself (particularly in its milder forms) is not inherently pathological and may be encountered in individuals 
for whom a diagnosis of ‘mental disorder’ would be inappropriate’ . (p. 8). Accordingly, the only diagnoses that do not include this criterion are those whose symptomatic presentations are considered to be inherently indicative of psychopathology (e.g., the psychotic disorders).
The diagnostic implications of this difference can be illustrated

The diagnostic implications of this difference can be illustrated 
in the different ways that speciﬁ  c phobia is deﬁ  ned in DSM-IV and 
ICD-10. In DSM-IV , a phobia is diagnosed only if ‘the avoidance, anxious anticipation, or distress in the feared situation interferes 
signiﬁ  cantly with the person’s normal routine, occupational (or 
academic) functioning or social activities or relationships, or there is marked distress about having the phobia’ . (p. 449, DSM-IV-TR). ICD-10 has no such requirement; the phobia is diagnosed so long as there is a marked fear or avoidance of a speciﬁ  c object or

situation. Thus, an individual residing in New Y ork City who has a snake phobia but who never has any occasion to encounter a snake would not be diagnosed as having a mental disorder in DSM-IV-TR because the phobia does not have any impact on the person’s func-tioning whereas in ICD-10 such an individual would be diagnosed as having a snake phobia because the person would react with fear or avoidance if he or she had the occasion to be confronted with a snake.
Separating symptoms from the functional impairment that

Separating symptoms from the functional impairment that 
results from them certainly makes conceptual sense. In other areas of medicine, the diagnosis of a disorder is based solely on the pres-ence of pathology and not on the effect that the pathology exerts on a person’s life (e.g., a patient is diagnosed with pneumococcal pneumonia if the patient’s lungs are infected with the pneumococ-cus bacillus regardless of the impact of the pneumonia on the patient’s level of functioning). The problem with diagnosing mental disorders in this way is that it is not currently possible to deﬁ ne the presence of a mental disorder based on the identiﬁ  cation 
of its underlying pathology. The descriptive symptoms that make up the deﬁ  nitions of mental disorders in the DSM-IV and ICD-10 
are not speciﬁ  c to mental disorders but can and do occur in 
individuals without any mental disorder. Thus, deﬁ  ning disorders 
exclusively in terms of presenting symptomatology, much of which

exclusively in terms of presenting symptomatology, much of which 
can occur in normal individuals, can lead to false positive diag-
noses. For this reason, in order to avoid false positive diagnoses in the absence of objective evidence of disease, DSM relies on func-tional impairment or distress to help set the diagnostic threshold between normality and disorder.
The structure of ICD-10, (Chapter V)
The psychiatric classification is part of the general medical classiﬁ  cation. There are 21 chapters, each designated by a Roman 
numeral. The psychiatric disorders are included in Chapter V which is also identiﬁ  ed by the letter F. The letter F is followed by

numeral. The psychiatric disorders are included in Chapter V which is also identiﬁ  ed by the letter F. The letter F is followed by 
Arabic numbers, the so-called second digit for the larger diagnostic groups and the third digit for more special groups. Thus the use of three digits allows a choice of 100 diagnostic possibilities. Proceeding further with a fourth digit, 1000 possible diagnoses are available, of which about one-third are used at present. This system is thus designed to allow the addition of new diagnoses in future without having to change substantial parts of the classiﬁ  cation.
Furthermore, it is possible to code the course over time or charac-
teristic features of a disorder by using a ﬁ  fth or sixth digit. By using 
codes from other chapters of ICD-10, such as X, Y, and Z, additional

103
circumstances (e.g. suicide) or special symptoms (e.g. nausea) as well 
as psychosocial factors can be coded. Somatic comorbidity is coded from the related chapters, for example diseases of ear, nose, and throat from Chapter VIII headed by the letter H (e.g. tinnitus H93.1) or diseases of the gastrointestinal system from Chapter XI headed by the letter K (e.g. alcohol gastritis K29.2). The speciﬁ  c challenges 
encountered in diagnosing psychiatric disorders reliably over the years has led WHO to include short deﬁ  nitions plus inclusion and 
exclusion terms for all psychiatric disorders in Chapter V (F). In all other chapters, diagnoses are named without further explanation.
As described earlier in this chapter, Chapter V of ICD-10 is not

As described earlier in this chapter, Chapter V of ICD-10 is not 
just a catalogue of disorders for statistical purposes, but is also a clinical manual, a textbook of diagnoses, and an instrument for research for different users. Therefore, a group of texts had to be produced to serve the various purposes—the so-called ‘ICD-10 family of documents’
The Short Glossary of ICD-10, Chapter V (F)  is part of the basic 
work known as the International Statistical Classiﬁ  cation of Diseases 
and Related Health Problems  The Short Glossary is part of the ﬁ  rst 
of three volumes, the general systematic classiﬁ  cation, and gives 
short deﬁ  nitions which are useful not only for medical personnel 
but also for statisticians, health insurance clerks, and others who are not in medical or related professions.
The Clinical Descriptions and Diagnostic Guidelines (CDDG 
Version) , known as the Blue Book because of the colour of its cover,

Version) , known as the Blue Book because of the colour of its cover, 
was developed ﬁ  rst and can be regarded as the central part of the 
psychiatric classiﬁ  cation
(14) intended for use by psychiatric clini-
cians in their daily practice. The Diagnostic Criteria for Research
(DCR), known as the Green Book, has been developed for scientiﬁ  c 
use(15) and is intended to be used together with the diagnostic 
guidelines. Compared with the Blue Book, the symptom criteria are more clearly deﬁ  ned, the time criteria are stricter, and the inclu-
sion and exclusion criteria are more precise in the Green Book. Thus, many unclear cases which are unsuitable for research are excluded. However, despite its title, this book is also useful for diag-nosticians in clinical practice. 
The multiaxial version  of the ICD-10 classiﬁ  cation of mental

The multiaxial version  of the ICD-10 classiﬁ  cation of mental 
disorders allows different aspects of the patient’s health and social situation to be assessed. Introduced by Rutter and colleagues,
(30)
multiaxial diagnosis has been employed for many years in child and adolescent psychiatry. It contains clinical syndromes, problems of development, intelligence, somatic disorders, and psychosocial prob-lems. T o a considerable degree, the multiaxial version of ICD-10 is comparable with that of DSM-IV . However, in DSM-IV , axis I is for psychiatric clinical disorders, axis II is for personality disorders and intellectual disability, and axis III is for general medical conditions. In ICD-10, axis I includes all disorders. Thus, psychiatric disorders (F1–F5), personality disorders (F6) and intellectual disability (F7), and the chapters on somatic comorbidity all use one axis.
Axis II of ICD-10 is for disability. T o facilitate its use, WHO devel-

oped an instrument, the short disability assessment schedule (WHO DAS-S), which helps to describe and assess the consequences of axis I disorders.
(31) Axis II corresponds to the widely used DSM-IV 
axis V , Global Assessment of Functioning (GAF). In connection with the disability axis, the International Classiﬁ  cation of Functioning 
created by WHO for the whole of rehabilitative medicine, of which psychiatry is only a part, should be mentioned.
(29) Axis III of 
ICD-10 covers psychosocial and other problems, and corresponds to DSM-IV axis IV (psychosocial and environmental problems).Theprimary health care  (PHC) version of the ICD-10 classiﬁ  cation 
of mental disorders was developed because of the great importance of psychiatric disorders in general practice, for example the high prevalence of depressions, anxiety disorders, and dependence on alcohol and psychotropic drugs.
(17) There are 24 syndromes,

(17) There are 24 syndromes, 
including dementia, delirium, depression, etc. Each disorder is understood in a rather broad sense, and not subdivided, and the descriptions are simpler than those in the main classiﬁ  cation. 
A ﬂ ipcard containing symptoms, diagnostic criteria, differential 
diagnoses, and counselling and treatment of the patient and the family is provided for every syndrome.
At ﬁ rst glance, the structure of ICD-10, Chapter V (F), follows 
that of ICD-8 or ICD-9 (See Appendix 1). The classiﬁ  cation begins 
with the ‘organic disorders’ , followed by disorders due to the abuse of psychoactive substances. The next section of the classiﬁ  cation 
contains schizophrenia and other psychotic disorders. This is fol-lowed by affective disorders and then neurotic and personality dis-orders. The chapter ends with intellectual disability and disorders of childhood and adolescence. Closer examination of the classiﬁ  ca-

tion reveals that the traditio nal dualistic principle—psychoses on 
the one hand (in ICD-9: codes 290–299) and neuroses on the other (in ICD-9: codes 300–310)—has been abandoned. The diagnostic terms now used take a more phenomenological descriptive approach. According to the authors of ICD-10, the same psychiat-ric disorder may show both psychotic and non-psychotic symp-toms. ‘Psychotic’ is deﬁ  ned as the manifestation of productive 
symptoms. The term ‘neurosis’ did not appear in the ﬁ  rst drafts of

symptoms. The term ‘neurosis’ did not appear in the ﬁ  rst drafts of 
ICD-10 because it is used in different and contradictory ways and is supposedly based on theories of intrapsychic processes which many of the WHO experts regarded as not generally accepted. However, after protests and objections by many clinicians world-wide, it was concluded that ‘psychotic’ and ‘neurotic’ should be used, although only as descriptive terms and not as diagnostic rubrics. Thus the term ‘neurotic disorders’ follows the traditional use of the word but does not imply an etiological theory.
(a) Organic, including symptomatic, mental disorders
Disorders of organic aetiology are grouped in this subchapter, independent of whether they contain psychotic or non-psychotic symptoms. However, the use of the term ‘organic’ does not imply that conditions elsewhere in the classiﬁ  cation are non-organic in 
the sense of having no cerebral substrate.
(b)  Mental and behavioural disorders due to psychoactive

(b)  Mental and behavioural disorders due to psychoactive 
substance use
An improvement over ICD-9 is the compilation of all mental and 
behavioural disorders due to psychoactive substances within a single subchapter. The third digit indicates which substance or class of substances (e.g. F10 Alcohol) is responsible for the disorder, which is coded as a fourth digit (e.g. F10.3 Alcohol withdrawal state) or a ﬁ  fth digit (e.g. F10.31 Alcohol withdrawal state with 
convulsions). It is possible to differentiate acute intoxication, harm-ful use, dependence syndrome, withdrawal state with or without delirium, different psychotic disorders, amnesic syndrome, and a number of other disorders. Thus, the psychopathological syndrome can be described and related to the dominant substance class.
(c) Schizophrenia, schizotypal, and delusional disorders

This subchapter covers schizophrenia, acute psychotic disorders, schizoaffective disorders, delusional disorders, and schizotypal 1.9 diagnosis and classification

SECTION 1  the subject matter of and approach to psychiatry 104
disorders. Before schizophrenia can be diagnosed the symptoms 
have to be observed for at least one month, unlike DSM-IV where symptoms should be observed for six months before using this diagnosis. Special care is taken with the description of short-lasting psychoses, since acute and transient psychotic disorders are of par-ticular interest to psychiatrists fr om developing c ountries where 
short-lasting acute psychoses with a good prognosis are observed 
quite frequently.
(d) Mood (affective) disorders

All mood disorders are combined in this subchapter, which repre-sents a considerable change compared with ICD-9. The disorders previously known as endogenous and neurotic depressions are coded in this subchapter; the differentiation between these catego-ries has been abandoned. The ICD-9 category of neurotic depres-sion (300.4) is no longer found in ICD-10; most of these cases are now coded as dysthymia (F34.1). Single manic episodes are coded as F30, while recurrent manic episodes are now coded as bipolar affective disorder (F31), regardless of whether or not there has been a previous depressive episode.
(e) Neurotic, stress-related, and somatoform disorders

The disorders in this subchapter are divided into a large number of categories. For instance, dissociative disorders are divided into seven subcategories, some of which represent rather rare disorders. The term hysteria is no longer used. In this subchapter, reactions to severe stress and adjustment disorders are enumerated according to time criteria and severity. Here, aetiology is generally accepted to mean exceptional mental stress or special life events. A new group of disorders in this classiﬁ  cation are the somatoform disorders, 
which are of particular importance in developing countries. The traditional term neurasthenia is still maintained for a special cate-gory, in contrast with DSM-IV .
(f)  Behavioural syndromes associated with physiological 
disturbances and physical factors
This subchapter brings together eating disorders, non-organic sleep

This subchapter brings together eating disorders, non-organic sleep 
disorders, sexual dysfunction, mental and behavioural disorders associated with the puerperium, and abuse of non-dependence-producing substances. In ICD-9, all sexual disorders were contained in one subchapter. In ICD-10, only disorders of sexual dysfunction are in F5; disorders of gender identity and sexual pref-erence have been assigned to two different sections in subchapter F6 on personality disorders. The special code F54, psychological and behavioural factors associated with disorders or diseases classi-ﬁ ed elsewhere, allows classiﬁ  cation of psychosomatic disorders by 
coding an additional somatic diagnosis.
(g) Disorders of adult personality and behaviour

Specific personality disorders are coded in this subchapter. Cyclothymic personality is not included, but an equivalent appears in F3 as cyclothymia. Also, schizotypal disorders could have been assigned to this subchapter but appear instead in F2 (as F21). The emotionally unstable personality disorder is found in this sub-chapter, where it is subdivided into an impulsive type (F60.30) and a borderline type (F60.31). A new entity is the factitious disorder, i.e. the intentional production or feigning of symptoms or disabilities, either physical or psychological (F68.1). If desired, narcissistic personality disorder and passive–aggressive personality disorder may be coded by using the criteria in Annex 1 of the Diagnostic Criteria for Research.An important aspect of this subchapter is the inclusion of

enduring personality changes after catastrophic experience (F62.0) or after psychiatric illness (F62.1). Personality changes after surviv-ing a concentration camp or torture are coded under the ﬁ  rst 
of these.
(h) Remaining subchapters
F7 intellectual disability, F8 Disorders of psychological develop-ment, and F9 Behavioural and emotional disorders with onset during childhood and adolescence are 
The structure of DSM-IV-TR
The ‘DSM-IV-TR Classiﬁ  cation of Mental Disorders’ refers to the 
comprehensive listing of the ofﬁ  cial diagnostic codes, categories, 
subtypes, and speciﬁ  ers (see Appendix 2). It is divided into various 
‘diagnostic classes’ which group disorders together based on com-mon presenting symptoms (e.g., mood disorders, anxiety disor-ders), typical age-at-onset (e.g., disorders usually ﬁ  rst diagnosed 
in infancy, childhood, and adolescence), and aetiology (e.g., sub-stance-related disorders, mental disorders due to a general medical condition).

Disorders usually ﬁ  rst diagnosed in infancy, 
childhood, or adolescence
The DSM-IV-TR classiﬁ  cation begins with disorders usually ﬁ  rst 
diagnosed in infancy, childhood, or adolescence. The inclusion of a separate ‘childhood disorders’ section in DSM-IV-TR is only for convenience—some of these conditions are sometimes diagnosed for the ﬁ  rst time in adulthood (e.g., attention-deﬁ  cit/
hyperactivity disorder) and many disorders included in the rest of DSM-IV-TR can start in childhood (e.g., major depressive disorder,

hyperactivity disorder) and many disorders included in the rest of DSM-IV-TR can start in childhood (e.g., major depressive disorder, 
schizophrenia). Thus, a psychiatrist doing a diagnostic assessment of a child or adolescent should not only focus on those disorders listed in this section but also consider disorders from throughout the DSM-IV-TR. Similarly, when evaluating an adult, the psychia-trist should also consider the disorders in this section since many of them persist into adulthood (e.g., stuttering, learning disorders, tic disorders).
While the ﬁ  rst set of disorders included in this section (i.e., 
intellectual disability learning and motor skills disorders, and

intellectual disability learning and motor skills disorders, and 
communication disorders) are not, strictly speaking, regarded as mental disorders they are included in the DSM-IV-TR to facilitate differential diagnosis. Autism and other pervasive developmental disorders are characterized by gross qualitative impairment in social relatedness, in language, and in repertoire of interests and activities and include autistic disorder, Asperger’s disorder, Rett’s disorder, and childhood disintegrative disorder. The Disruptive Behaviour Disorders (i.e. Attention-deﬁ  cit/hyperactivity disorder, 
conduct disorder, and oppositional-deﬁ  ant disorder) are grouped

conduct disorder, and oppositional-deﬁ  ant disorder) are grouped 
together because they are all characterized (at least in their child-hood presentations) by disruptive behavior. The Feeding Disorders of Infancy and Early Childhood include the DSM-IV-TR categories of pica, rumination disorder, and feeding disorder of infancy and early childhood (also known as failure to thrive). Tic disorders, elimination disorders, and other disorders of infancy and early child-hood (which include separation anxiety disorder, selective mutism, reactive attachment disorder, and stereotypic movement disorder) round out the childhood section.

105
Delirium, dementia, amnestic disorder, and 
other cognitive disorders
In DSM-III-R, delirium, dementia, amnestic disorder, and other 
cognitive disorders, along with substance-induced mental disor-ders and mental disorder due to a general medical condition, were included in a section called ‘organic mental disorders’ , which contained all disorders that were due to either a general medical condition or substance use. In DSM-IV , the term ‘organic’ was completely eliminated from the classiﬁ  cation because of the mis-
leading implication that disorders not included in that section (e.g., schizophrenia, bipolar disorder) did not have an organic component
(32). In fact, virtually all mental disorders have both psy-
chological and biological components, and to designate some dis-orders as ‘organic’ and the remaining disorders in the DSM-IV as ‘non-organic’ reﬂ  ected a reductionistic mind-body dualism.
As a result of the elimination of the Organic Mental Disorder

As a result of the elimination of the Organic Mental Disorder 
diagnostic grouping, those disorders originally included in that section had to be redistributed throughout DSM-IV into other diagnostic classes. Delirium, dementia, and amnestic disorder were thus grouped together into a major diagnostic class because of their central roles in the differential diagnosis of cognitive impairment. Although both delirium and dementia are characterized by multi-ple cognitive impairments, delirium is distinguished by the presence of clouding of consciousness which is manifested by an inability to appropriately maintain or shift attention. Three types of delirium 
are included in DSM-IV based on causative factors: delirium due 
to a general medical condition, substance-induced delirium, and delirium due to multiple etiologies.
Dementia is deﬁ  ned by clinically signiﬁ  cant memory impairment

Dementia is deﬁ  ned by clinically signiﬁ  cant memory impairment 
accompanied by impairment in one or more other areas of cogni-tive functioning (e.g. language, executive functioning). DSM-IV-TR includes several types of dementia based on aetiology, including dementia of the Alzheimer’s type, vascular dementia, a variety of dementia due to general medical and neurological conditions (e.g., HIV , Parkinson’s disease), substance-induced persisting dementia, and dementia due to multiple etiologies. In contrast to dementia, amnestic disorder is characterized by memory impairment occur-ring in the absence of other cognitive impairments. Two types are included in DSM-IV: amnestic disorder due to a general medical condition and substance-induced persisting amnestic disorder.
Mental disorders due to a general medical 
condition not elsewhere classiﬁ  ed

In DSM-IV-TR, most of the mental disorders due to a general medi-
cal condition have been distributed alongside their ‘non-organic’ counterparts in the classiﬁ  cation (e.g. mood disorder due to a gen-
eral medical condition and substance-induced mood disorder was included in the mood disorders section). Two speciﬁ  c types of men-
tal disorders due to a general medical condition (i.e. catatonic disor-der due to a general medical condition and personality change due to a general medical condition) do not ﬁ  t into any of the other diagnos-
tic classes and therefore, are included here in this diagnostic class.
Substance-related disorders
In DSM-IV , substance-related disorders include psychiatric distur-bances that result from medication side effects and the consequences of toxin exposure, in addition to those that arise due to drug and

alcohol abuse. Two types of substance-related disorders are includ-ed in DSM-IV: substance use disorders (dependence and abuse), which focus on the maladaptive nature of the pattern of substance use; and substance-induced disorders, which cover psychopatho-logical processes caused by the direct effects of substances (including toxins and medications) on the central nervous system.
Schizophrenia and other psychotic disorders
Included in this grouping are those disorders in which psychosis is the primary characteristic symptom (i.e. schizophrenia, schizo-phreniform disorder, schizoaffective disorder, delusional disorder, shared psychotic disorder and brief psychotic disorder). It should be noted that other disorders that may have psychotic features are not included in this grouping (e.g. mood disorders with psychotic features, delirium).
Mood disorders

This diagnostic class includes disorders in which the predominant disturbance is in the individual’s mood. Although the term ‘mood’ is generally considered to include emotions such as depression, euphoria, anger, and anxiety, DSM-IV includes in this section only disorders characterized by depressed, elevated, or irritable mood. This diagnostic class is further divided into depressive and bipolar disorders. The term ‘bipolar’ is misleading because the name implies the presence of both ‘down’ and ‘up’ moods. In fact, bipolar disorder is deﬁ  ned by the presence of one or more manic or hypo-
manic episodes. Thus, patients with multiple manic episodes (i.e. unipolar mania) are considered to be bipolar despite the lack of the second ‘pole’ .
Anxiety disorders
The common thread tying together disorders in this section is the fact that the clinical presentation of these disorders is typically characterized by signiﬁ  cant anxiety. The rationale for this grouping

has been criticized because of evidence suggesting that at least some of the disorders are likely to be etiologically distinct from the others. For example, it has been argued that obsessive-compulsive disorder is most likely part of an obsessive-compulsive spectrum that might include tic disorders, hypochondriasis, body dysmorphic disorder, and perhaps trichotillomania.
(33)
Somatoform disorders

(33)
Somatoform disorders are characterized by their presentation in gen-eral medical settings by individuals who do not consider themselves to be suffering from a mental disorder. Individuals with somatoform disorders present with somatic complaints or bodily concerns that are not adequately explained by an underlying general medical condition. Conceptually, the somatoform disorders can be divided into three general types: 1) those in which the individual’s focus is on the physi-cal symptoms themselves (somatization disorder, undifferentiated somatoform disorder, pain disorder, and conversion disorder); 2) those who are preoccupied by the belief that one has a serious physi-cal illness despite medical reassurance (hypochondriasis); and 3) 
those who are preoccupied by the belief that a part or parts of their 
body are physically defective (body dysmorphic disorder).1.9 diagnosis and classification

SECTION 1  the subject matter of and approach to psychiatry 106
Factitious disorders
Individuals with a factitious disorder intentionally produce or feign 
a physical or psychological symptom, motivated by the psychologicalneed to assume the sick role and be taken care of. This is in contrast to malingering (which is not considered to be a mental disorder) in which the person is motivated by secondary gain (e.g. to evade criminal responsibility, to receive disability beneﬁ  ts).
Dissociative disorders
Dissociation is the core element of this group of disorders, which is 
deﬁ ned as a disruption in the usually integrated functions of 
consciousness, memory, identity, and perception. Four speciﬁ  c 
disorders are included (dissociative amnesia, dissociative fugue, dissociative identity disorder, and depersonalization disorder).
Sexual and gender identity disorders

This diagnostic class groups together disorders involving three relatively distinct aspects of human sexuality: sexual dysfunctions, which involve disturbances in sexual desire or functioning, para-philias which involve unusual sexual preferences that interfere with functioning (or in the case of preferences that involve harm to others like paedophilia, merely acting on those preferences), and gender identity disorder that entail one’s internal identity of maleness and femaleness (gender identity) being at odds with one’s anatomical sexual characteristics.
Eating disorders

Disorders in this section involve abnormal eating behavior; either the refusal to maintain adequate body weight (anorexia nervosa) or discrete episodes of uncontrolled eating accompanied by excessive effects to counteract the effects of these binges (bulimia nervosa).
Sleep disorders
Sleep disorders are subdivided into four groups based on presumed aetiology (primary, related to another mental disorder, due to a general medical condition, and substance induced). Two types of primary sleep disorders have been included: dyssomnias (problems in regulation of amount and quality of sleep) and parasomnias (events that occur during sleep). The dyssomnias include primary insomnia, primary hypersomnia, circadian rhythm sleep disorder, narcolepsy, and breathing-related sleep disorder, whereas the parasomnias include nightmare disorder, sleep terror disorder, and sleepwalking disorder.
Impulse control disorders not 
elsewhere classiﬁ  ed

Many disorders in the DSM-IV-TR are characterized by problems 
with impulse control (e.g. borderline personality disorder, substance dependence, attention-deﬁ  cit/hyperactivity disorder). This diag-
nostic grouping is for those impulse-control disorders not included in other sections of the DSM-IV-TR. Included are problems controlling angry impulses (intermittent explosive disorder), problems controlling impulses to steal (kleptomania) or set ﬁ  res 
(pyromania), problems controlling impulses to pull out one’s hair (trichotillomania) and problems controlling impulses to gamble 
(pathological gambling).
Adjustment disorders
This diagnostic class is for presentations that do not meet criteria for speciﬁ  c disorders (i.e. subthreshold presentations) that represent

This diagnostic class is for presentations that do not meet criteria for speciﬁ  c disorders (i.e. subthreshold presentations) that represent 
a maladaptive response to a stressor. For example, if depression occurring after a job loss is severe enough to meet full symptomatic criteria for a major depressive episode, then major depressive disorder would be diagnosed. If the job-loss-related depression falls symptomatically short of this diagnostic threshold, then adjustment disorder with depressed mood is diagnosed.
Personality disorders
Each of us has a personality, that is our characteristic way of experiencing and processing the world and ourselves. When an individual’s characteristic patterns of relating, feeling, and thinking are so inﬂ  exible and maladaptive that they interfere

with his or her functioning, then that person is considered to have a personality disorder. 10 specific personality disorders are included in DSM-IV-TR: paranoid personality disorder (pervasive distrust and suspiciousness of others), schizoid personality dis-order (lack of desire for social relationships and a restricted expression of emotions), schizotypal personality disorder (acute discomfort with close relationships, odd beliefs, perceptual distor-tions, and eccentricities of behaviour), antisocial personality disor-der (disregard for the rights of others), borderline personality disorder (instability of personal relationships and self-image, fears of abandonment, and marked impulsivity), histrionic personality disorder (extensive emotionality and attention seeking), narcissis-tic personality disorder (grandiosity, need for admiration, and lack of empathy), avoidant personality disorder (social inhibition, and hypersensitivity to negative evaluation), dependent personality

personality disorder (grandiosity, need for admiration, and lack of empathy), avoidant personality disorder (social inhibition, and hypersensitivity to negative evaluation), dependent personality disorder (excessive need to be taken care of), and obsessive-compulsive personality disorder (preoccupation with orderliness, perfectionism, stubbornness).

Research planning for DSM-V 
and ICD-11
It is currently anticipated that the DSM-V will be published in 2012 
and that the ICD-11, although likely to be in a ﬁ  nal draft form around 
the same time, will be ofﬁ  cially published a few years later after 
approval by the WHO Assembly. When the last major revision of the DSM, DSM-IV , was published in 1994, the American Psychiatric Association decided to hold off on starting work on the next revision of the DSM until at least 2010, at least partly in response to the criti-cism that the seven year interval between prior versions of the DSM was too short.
(34) Similarly, resistance to the implementation of ICD-

10 by many countries (including the United States) ensured that the next revision of the ICD would also be put off for a number of years. The American Psychiatric Association decided to take advantage of this delay in the diagnostic revision process by partnering with the National Institute of Mental Health and the World Health Organization in order to initiate a research planning process with the aim of stimu-lating potentially informative research prior to the formal beginning of the DSM-V and ICD-11 revision processes.

107
Part of the impetus for encouraging research in advance of the 
next diagnostic revision is the general frustration felt by both researchers and clinicians with the superficially descriptive approach taken by DSM-IV and ICD-10. Although the operation-alized criteria in DSM-III were developed based largely on expert consensus, there was a general understanding that the categories would continually be revised and improved in future editions of the DSM, ultimately culminating in the identiﬁ  cation of the under-
lying disease processes.
Unfortunately, in the more than 25 years since the publication of 
DSM-III, the goal of validating these syndromes and discovering the underlying pathophysiology has remained elusive. Despite many proposed candidates, not one laboratory marker has been found to be diagnostically useful for any DSM category.
(35) Epidemiological

(35) Epidemiological 
and clinical studies have shown extremely high rates of comorbidi-ties among the disorders, undermining the hypotheses that these syndromes represent distinct etiologies. Regarding treatment, lack of treatment speciﬁ  city is the rule: SSRI’s effective for treating disor-
ders across the diagnostic spectrum (e.g. depression, panic, general-ized anxiety disorder, posttraumatic stress disorder, social anxiety, body dysmorphic disorder, obsessive-compulsive disorder, patho-logical gambling, trichotillomania, borderline personality disorder, etc.). Results of twin studies have also contradicted DSM-IV’s assumptions that separate syndromes have a distinct underlying genetic basis (e.g. major depressive disorder and generalized anxiety disorder have the same genetic risk factors).
The considerable limitations of the DSM paradigm have fueled 
the desire that DSM-V and ICD-11 would be etiologically-based

the desire that DSM-V and ICD-11 would be etiologically-based 
rather just descriptive. The main barrier to making DSM-V and ICD-11 more etiological is, of course, the enormous gaps in our understanding of the pathophysiology of mental disorders. Therefore, in order to help move the ﬁ  eld forward towards the goal 
of a primarily etiological classiﬁ  cation, a series of ‘white papers’

of a primarily etiological classiﬁ  cation, a series of ‘white papers’ 
was commissioned under joint sponsorship of the American Psychiatric Association, the National Institute of Mental Health (NIMH), National Institute for Alcoholism and Alcohol Abuse (NIAAA), and the National Institute for Drug Abuse (NIDA). Research planning workgroups responsible for the development of these white papers were constituted for two primary reasons: 1) to stimulate research that will enrich the empirical data base prior to the start of the DSM-V revision process; and 2) to devise a research and analytic agenda that would facilitate the integration of ﬁ  ndings 
from animal studies, genetics, neuroscience, epidemiology, clinical research, cross-cultural research, and clinical services research, which will lead to the eventual development of an etiologically-based, scientiﬁ  cally-sound classiﬁ  cation system. In order to encour-

age thinking beyond the current DSM-IV framework, most of the workgroup members had not been closely involved in the DSM-IV development process. Furthermore, rather than organizing the 
white paper workgroups around the traditional diagnostic catego-
ries, the workgroups focused instead on cross-cutting issues, which included 1) a basic nomenclature workgroup, focusing on a variety of issues that had to do with the way disorders are classiﬁ  ed in the 
DSM; 2) a neuroscience and genetics workgroup whose focus was to develop a basic and clinical neuroscience and genetics research 
agenda to guide the development of a future pathophysiologically-
based classiﬁ  cation; 3) a developmental science workgroup which 
outlined a research agenda to inform developmental aspects of the diagnostic classiﬁ  cation; 4) a workgroup focusing on two major gaps in the DSM-IV , namely inadequacies in the classiﬁ  cation 
of personality disorders and of relational disorders; 5) a mental

of personality disorders and of relational disorders; 5) a mental 
disorders and disability workgroup which focused on disentangling the concepts of symptom severity and disability; and 6) a culture and psychiatric diagnosis workgroup which considered cross-cultural issues in diagnosis and classiﬁ  cation. It should be noted 
that given the breakthrough nature of the suggested research and the relatively short time frame leading up to the anticipated publi-cation of DSM-V and ICD-11, it was understood that most of the proposed research agenda was unlikely to bear fruit until DSM-VI/ICD-12 or later.
The six white papers were published by American Psychiatric 
Publishing, Inc. in 2002 in a monograph entitled ‘A Research Agenda for DSM-V’ .
(36) Three additional white papers, one focus-

ing on gender issues, one focusing on diagnostic issues in the geri-atric population, and one focusing on mental disorders in infants and young children were commissioned subsequently and appear in a second volume of the research agenda.
(37)
The second phase of the DSM-V Research Planning Process con-
sisted of 11 research planning conferences (plus a methods confer-ence) that occurred from 2004 to 2007. These conferences were being organized with the assistance and support of the World Health Organization and are co-funded by APA, NIMH, NIAAA, and NIDA. Unlike the white papers in the ﬁ  rst phase which focused 
on general cross-cutting issues, these conferences for the most part focussed on speciﬁ  c diagnostic topics. The primary goals of these

on general cross-cutting issues, these conferences for the most part focussed on speciﬁ  c diagnostic topics. The primary goals of these 
conferences were to stimulate the empirical research necessary to allow informed decision-making regarding crucial diagnostic deﬁ  -
ciencies identiﬁ  ed in DSM-IV and ICD-10, and to promote inter-
national collaboration in order to increase the likelihood of devel-oping a future uniﬁ  ed DSM/ICD (i.e. each conference had two 
co-chairs, one from the United States and the other outside the US, 
each conference included an equal number of the US and interna-

tional participants, and half the conferences took place outside the US). Conference topics were selected after consultation with the US and international experts. Finite resources necessitated that the number of conferences be limited to a total of 11 (and the number of participants to 25); thus a number of potentially important top-ics could not be included. The 11 diagnostic-topic focused confer-ences covered Dimensional Approaches Personality Disorders (December 2004, Arlington, V A);
(38) Substance-Related Disorders 
(February 2005, Rockville, MD);(39) Stress-Induced and Fear 
Circuitry Disorders (June 2005, Arlington, V A); Dementia (September 2005, Geneva, Switzerland),
(40) Deconstructing 
Psychosis (February 2006, Arlington, V A);(41) Obsessive-Compulsive 
Spectrum Disorders (June 2006, Arlington, V A);(33) Dimensional

Spectrum Disorders (June 2006, Arlington, V A);(33) Dimensional 
Approaches to Diagnosis (July 2006, Bethesda, MD);(42) Somatic 
Presentations (September 2006, Beijing, China); Externalizing Disorders of Childhood (February 2007, Mexico City); Comorbidity 
of Anxiety and Depression (June 2007, London, UK), and Public 
Health Implications (September 2007, Geneva, Switzerland). An additional conference on Autism spectrum disorders was also con-vened in Sacramento, CA in February 2008. Summaries of the  conferences are available on the DSM-V website: www.dsm5.org.
The future
Despite the ubiquitous desire to move from a descriptive classiﬁ  ca-
tion system to an etiologically-based classiﬁ  cation system deﬁ  ned 1.9 diagnosis and classification

SECTION 1  the subject matter of and approach to psychiatry 108
by objective laboratory ﬁ  ndings, results of the research planning 
process indicate that disorders in DSM-V and ICD-11 will continue to be deﬁ  ned based on descriptive symptomatology. Despite the 
advances in neuroimaging, genetics, and biological markers over the past 10 years, it is unlikely that any objective laboratory ﬁ  ndings will 
be part of the deﬁ  nition of any DSM-V or ICD-11 disorder, with the 
one exception being polysomnography ﬁ  ndings to deﬁ  ne sleep dis-
orders given that such ﬁ  ndings are already part of the diagnostic 
deﬁ nitions of sleep disorders in the International Classiﬁ  cation of 
Sleep Disorders – 2nd Edition (ICSD-2).
(43) Although research 
studies have reliably demonstrated differences in a wide variety of objective measures between groups of affected individuals and con-trols (for example, brain ventricular size in individuals with schizo-phrenia as compared to unaffected controls),

(44) when it comes 
down to applying the ﬁ  ndings to a particular individual for the pur-
pose of making a diagnosis, none of these ﬁ  ndings have been shown 
to be sufﬁ  ciently sensitive or speciﬁ  c.
A central question being raised as part of the DSM-V/ICD-11 
revision process is whether psychiatric diagnosis would be better served by a dimensional approach rather than the cur rent cat egorical 
approach. This topic was the exclusive focus of one of the 11 research planning conferences being held in advance of the DSM-V/ICD-11 revision (i.e. ‘Dimensional Approaches in Diagnostic Classiﬁ  cation: A Critical Appraisal’ , held in Arlington V A, July 27–
28, 2006)
(42), was the main focus of the Personality Disorders 
Research Planning conference which proposed a research agenda for adopting a dimensional approach to personality disorders
(45)

28, 2006)
(45)
and was a important component of the other diagnostic-related conferences (e.g. ‘Should there be both categorical and dimensional criteria for the substance use disorders in DSM-V’ .
(46)) Much of the 
impetus for moving toward a dimensional approach comes from dissatisfaction with categorical diagnoses expressed by the research community.
(47–58) There are a number of persuasive arguments 
for the superiority of a dimensional approach over a categorical one, including, 1) the lack of evidence for discrete breaks or demar-cations in distributions of symptoms; 2) evidence of a superior ﬁ  t

of empirical data to latent structuring models that correspond to dimensional vs. categorical approaches; 3) higher levels of diag-nostic reliability and stability over time; and 4) elimination of the problematic artifacts of the categorical system, like excessive diagnostic comorbidity and arbitrary diagnostic thresholds.
(59)
On the other hand, a categorical approach to diagnosis remains critically important because of its clinical and administrative utility. Clinicians typically must make dichotomous decisions in everyday practice (i.e. whether to treat or not treat, to hospitalize or not hospitalize, to refer or not refer, etc.) and need to assign diagnostic categories to their patients for the purposes of reimbursement.
(60) Categorical labels also facilitate clinical com-
munication by providing a convenient shorthand when discussing 
a patient’s diagnosis (e.g. it is more efﬁ  cient for a clinician to use a

a patient’s diagnosis (e.g. it is more efﬁ  cient for a clinician to use a 
single diagnostic term when talking about a patient who has a borderline personality disorder rather than having to describe all the dimensions that went into that summary judgment). Given the relative advantages of each approach, DSM-V and ICD-11 will most likely adopt some sort of hybrid approach, retaining the categorical diagnoses for communication and decision-making purposes but also providing accompanying dimensions.
Finally, there is a strong push for DSM-V and ICD-11 to become 
more developmentally focused. ICD-10 and DSM-IV provide deﬁ nitions of mental disorders that, as far as possible, are applica-
ble across age groups. Given that most disorders can occur at any time during an individual’s lifespan, for the most part, the deﬁ  ni-

tions of disorder ignore developmental variations in presentation. It should be noted that DSM-IV does include some age-appropri-ate modiﬁ  cations in the diagnostic deﬁ  nitions (e.g. in PTSD, crite-
rion B(1), ‘recurrent and intrusive distressing recollections of the event, including images, thoughts, or perceptions’ is supplemented by ‘in young children, repetitive play may occur in which themes or aspects of the trauma are expressed’), these modiﬁ  cations are the 
exceptions. It is anticipated that DSM-IV and ICD-11 will pay con-siderably more attention to these issues, reviewing longitudinal studies that track the evolution of disorders across the lifespan and also consider whether deﬁ  nitions should be modiﬁ  ed to take into 
account developmental context.
Appendix 1
International classiﬁ  cation of diseases, 10th revision

Appendix 1
F00–F09 Organic, including symptomatic, mental disorders
F00 Dementia in Alzheimer’s disease
F00.0 Dementia in Alzheimer’s disease with early onset
F00.1 Dementia in Alzheimer’s disease with late onsetF00.2 Dementia in Alzheimer’s disease, atypical or mixed typeF00.9 Dementia in Alzheimer’s disease, unspeciﬁ  ed
F01 Vascular dementia
F01.0 Vascular dementia of acute onset
F01.1 Multi-infarct dementiaF01.2 Subcortical vascular dementiaF01.3 Mixed cortical and subcortical vascular dementiaF01.8 Other vascular dementiaF01.9 Vascular dementia, unspeciﬁ  ed
F02 Dementia in other diseases classiﬁ  ed elsewhere
F02.0 Dementia in Pick’s disease
F02.1 Dementia in Creutzfeldt–Jakob diseaseF02.2 Dementia in Huntington’s diseaseF02.3 Dementia in Parkinson’s diseaseF02.4 Dementia in human immunodeficiency virus (HIV) 
disease
F02.8 Dementia in other speciﬁ  ed diseases classiﬁ  ed elsewhere

disease
F03 Unspeciﬁ  ed dementia
A ﬁ fth character may be added to specify dementia in F00–F03, 
as follows:
.x0 Without additional symptoms
.xl Other symptoms, predominantly delusional
.x2 Other symptoms, predominantly hallucinatory
.x3 Other symptoms, predominantly depressive
.x4 Other mixed symptoms
F04 Organic amnesic syndrome, not induced by alcohol and 
other psychoactive substances
F05 Delirium, not induced by alcohol and other psychoactive 
substances
F05.0 Delirium, not superimposed on dementia, so described
F05.1 Delirium, superimposed on dementiaF05.8 Other deliriumF05.9 Delirium, unspeciﬁ  ed

109
F06 Other mental disorders due to brain damage and 
dysfunction and to physical disease
F06.0 Organic hallucinosis
F06.1 Organic catatonic disorderF06.2 Organic delusional (schizophrenia-like) disorderF06.3 Organic mood (affective) disorders
.30 Organic manic disorder.31 Organic bipolar disorder.32 Organic depressive disorder.33 Organic mixed affective disorder
F06.4 Organic anxiety disorder
F06.5 Organic dissociative disorder
F06.6 Organic emotionally labile (asthenic) disorderF06.7 Mild cognitive disorderF06.8 Other speciﬁ  ed mental disorders due to brain damage 
and dysfunction and to physical diseaseF06.9 Unspeciﬁ  ed mental disorder due to brain damage and 
F09 Unspeciﬁ  ed organic or symptomatic mental disorder
F07 Personality and behavioural disorders due to brain disease, 
damage and dysfunction
F07.0 Organic personality disorder

F07.1 Postencephalitic syndromeF07.2 Postconcussional syndromeF07.8 Other organic personality and behavioural disorders due 
to brain disease, damage, and dysfunction
F07.9 Unspeciﬁ  ed organic personality and behavioural disorder 
due to brain disease, damage, and dysfunction
F10–F19 Mental and behavioural disorders due to psychoactive 
F10 Mental and behavioural disorders due to use of alcohol

F11 Mental and behavioural disorders due to use of opioidsF12 Mental and behavioural disorders due to use of cannabinoidsF13 Mental and behavioural disorders due to use of sedatives or hypnoticsF14 Mental and behavioural disorders due to use of cocaineF15 Mental and behavioural disorders due to use of other stim-ulants, including caffeineF16 Mental and behavioural disorders due to use of hallucinogensF17 Mental and behavioural disorders due to use of tobaccoF18 Mental and behavioural disorders due to use of volatile solventsF19 Mental and behavioural disorders due to multiple drug use and use of other psychoactive substances
Four- and ﬁ  ve-character categories may be used to specify the 
clinical conditions, as follows
F1x.0 Acute intoxication

.00 Uncomplicated.01 With trauma or other bodily injury.02 With other medical complications.03 With delirium.04 With perceptual distortions.05 With coma.06 With convulsions.07 Pathological intoxication
F1x.1 Harmful use
F1x.2 Dependence syndrome
.20 Currently abstinent.21 Currently abstinent, but in a protected environment
.22 Currently on a clinically supervised maintenance or replacement regime (controlled dependence).23 Currently abstinent, but receiving treatment with aversive or blocking drugs.24 Currently using the substance (active dependence).25 Continuous use.26 Episodic use (dipsomania)
F1x.3 Withdrawal state
.30 Uncomplicated.31 Convulsions
F1x.4 Withdrawal state with delirium
.40 Without convulsions.41 With convulsions
F1x.5 Psychotic disorder

.50 Schizophrenia-like.51 Predominantly delusional.52 Predominantly hallucinatory.53 Predominantly polymorphic.54 Predominantly depressive symptoms.55 Predominantly manic symptoms.56 Mixed
F1x.6 Amnesic syndrome
F1x.7 Residual and late-onset psychotic disorder
.70 Flashbacks.71 Personality or behaviour disorder.72 Residual affective disorder.73 Dementia.74 Other persisting cognitive impairment.75 Late-onset psychotic disorder
F1x.8 Other mental and behavioural disorders
F1x.9 Unspeciﬁ  ed mental and behavioural disorder
F20–F29 Schizophrenia, schizotypal, and delusional disorders
F20 Schizophrenia
F20.0 Paranoid schizophrenia

F20.1 Hebephrenic schizophreniaF20.2 Catatonic schizophreniaF20.3 Undifferentiated schizophreniaF20.4 Post-schizophrenic depressionF20.5 Residual schizophreniaF20.6 Simple schizophreniaF20.8 Other schizophreniaF20.9 Schizophrenia, unspeciﬁ  ed
A ﬁ fth character may be used to classify course
 x0 Continuous
.x1 Episodic with progressive deﬁ  cit
.x2 Episodic with stable deﬁ  cit
.x3 Episodic remittent
.x4 Incomplete remission
.x5 Complete remission
.x8 Other
.x9 Period of observation less than one year
F21 Schizotypal disorder
F22 Persistent delusional disorders
F22.0 Delusional disorder
F22.8 Other persistent delusional disordersF22.9 Persistent delusional disorder, unspeciﬁ  ed1.9 diagnosis and classification

SECTION 1  the subject matter of and approach to psychiatry 110
F23 Acute and transient psychotic disorders
F23.0 Acute polymorphic psychotic disorder without symptoms 
of schizophreniaF23.1 Acute polymorphic psychotic disorder with symptoms of schizophreniaF23.2 Acute schizophrenia-like psychotic disorderF23.3 Other acute predominantly delusional psychotic disordersF23.8 Other acute and transient psychotic disordersF23.9 Acute and transient psychotic disorders unspeciﬁ  ed
A ﬁ fth character may be used to identify the presence or absence of 
associated acute stress
.x0 Without associated acute stress
.x1 With associated acute stress
F24 Induced delusional disorder
F25 Schizoaffective disorders
F25.0 Schizoaffective disorder, manic type
F25.1 Schizoaffective disorder, depressive typeF25.2 Schizoaffective disorder, mixed typeF25.8 Other schizoaffective disordersF25.9 Schizoaffective disorder, unspeciﬁ  ed
F28 Other non-organic psychotic disorders
F29 Unspeciﬁ  ed non-organic psychosis

F30–F39 Mood (affective) disorders
F30 Manic episode
F30.0 HypomaniaF30.1 Mania without psychotic symptomsF30.2 Mania with psychotic symptomsF30.8 Other manic episodesF30.9 Manic episode, unspeciﬁ  ed
F31 Bipolar affective disorder
F31.0 Bipolar affective disorder, current episode hypomanic
F31.1 Bipolar affective disorder, current episode manic without psychotic symptomsF31.2 Bipolar affective disorder, current episode manic with psychotic symptomsF31.3 Bipolar affective disorder, current episode mild or moder-ate depression
.30 Without somatic symptoms.31 With somatic symptoms
F31.4 Bipolar affective disorder, current episode severe depres-sion without psychotic symptomsF31.5 Bipolar affective disorder, current episode severe depres-sion with psychotic symptomsF31.6 Bipolar affective disorder, current episode mixed
F31.7 Bipolar affective disorder, currently in remission

F31.8 Other bipolar affective disordersF31.9 Bipolar affective disorder, unspeciﬁ  ed
F32 Depressive episode
F32.0 Mild depressive episode
.00 Without somatic symptoms.01 With somatic symptoms
F32.1 Moderate depressive episode
.10 Without somatic symptoms.11 With somatic symptoms
F32.2 Severe depressive episode without psychotic symptomsF32.3 Severe depressive episode with psychotic symptomsF32.8 Other depressive episodes
F32.9 Depressive episode, unspeciﬁ  ed
F33 Recurrent depressive disorder
F33.0 Recurrent depressive disorder, current episode mild
F33.1 Recurrent depressive disorder, current episode moderate

F33.2 Recurrent depressive disorder, current episode severe without psychotic symptomsF33.3 Recurrent depressive disorder, current episode severe with psychotic symptomsF33.4 Recurrent depressive disorder, currently in remissionF33.8 Other recurrent depressive disordersF33.9 Recurrent depressive disorder, unspeciﬁ  ed
F34 Persistent mood (affective) disorders
F34.0 Cyclothymia
F34.1 DysthymiaF34.8 Other persistent mood (affective) disordersF34.9 Persistent mood (affective) disorder, unspeciﬁ  ed
F38 Other mood (affective) disorders
F38.0 Other single mood (affective) disorders
.00 Mixed affective episode
F38.1 Other recurrent mood (affective) disorders
.10 Recurrent brief depressive disorder
F38.8 Other speciﬁ  ed mood (affective) disorders
F39 Unspeciﬁ  ed mood (affective) disorder

F40–F48 Neurotic, stress-related, and somatoform disorders
F40 Phobic anxiety disorders
F40.0 Agoraphobia
.00 Without panic disorder.01 With panic disorder
F40.1 Social phobiasF40.2 Speciﬁ  c (isolated) phobias
F40.8 Other phobic anxiety disordersF40.9 Phobic anxiety disorder, unspeciﬁ  ed
F41 Other anxiety disorders
F41.0 Panic disorder (episodic paroxysmal anxiety)
F41.1 Generalized anxiety disorderF41.2 Mixed anxiety and depressive disorderF41.3 Other mixed anxiety disordersF41.8 Other speciﬁ  ed anxiety disorders
F41.9 Anxiety disorder, unspeciﬁ  ed
F42 Obsessive-compulsive disorder
F42.0 Predominantly obsessional thoughts or ruminations

F42.1 Predominantly compulsive acts (obsessional rituals)F42.2 Mixed obsessional thoughts and actsF42.8 Other obsessive-compulsive disordersF42.9 Obsessive-compulsive disorder, unspeciﬁ  ed
F43 Reaction to severe stress, and adjustment disorders
F43.0 Acute stress reaction
F43.1 Post-traumatic stress disorderF43.2 Adjustment disorders
.20 Brief depressive reaction

111
.21 Prolonged depressive reaction
.22 Mixed anxiety and depressive reaction.23 With predominant disturbance of other emotions.24 With predominant disturbance of conduct.25 With mixed disturbance of emotions and conduct.28 With other speciﬁ  ed predominant symptoms
F43.8 Other reactions to severe stressF43.9 Reaction to severe stress, unspeciﬁ  ed
F44 Dissociative (conversion) disorders
F44.0 Dissociative amnesia
F44.1 Dissociative fugueF44.2 Dissociative stuporF44.3 Trance and possession disordersF44.4 Dissociative motor disordersF44.5 Dissociative convulsionsF44.6 Dissociative anaesthesia and sensory lossF44.7 Mixed dissociative (conversion) disordersF44.8 Other dissociative (conversion) disorders
.80 Ganser’s syndrome.81 Multiple personality disorder.82 Transient dissociate (conversion) disorders occurring in childhood and adolescence.88 Other speciﬁ  ed dissociative (conversion) disorders
F44.9 Dissociative (conversion) disorder, unspeciﬁ  ed
F45 Somatoform disorders

F45.0 Somatization disorder
F45.1 Undifferentiated somatoform disorderF45.2 Hypochondriacal disorderF45.3 Somatoform autonomic dysfunction
.30 Heart and cardiovascular system.31 Upper gastrointestinal tract.32 Lower gastrointestinal tract.33 Respiratory system.34 Genitourinary system.38 Other organ or system
F45.4 Persistent somatoform pain disorderF45.8 Other somatoform disordersF45.9 Somatoform disorder, unspeciﬁ  ed
F48 Other neurotic disorders
F48.0 Neurasthenia
F48.1 Depersonalization-derealization syndromeF48.8 Other speciﬁ  ed neurotic disorders
F48.9 Neurotic disorder, unspeciﬁ  ed
F50–F59 Behavioural syndromes associated with physiological 
F50 Eating disorders
F50.0 Anorexia nervosa

F50.1 Atypical anorexia nervosaF50.2 Bulimia nervosaF50.3 Atypical bulimia nervosaF50.4 Overeating associated with other psychological disturbancesF50.5 Vomiting associated with other psychological disturbancesF50.8 Other eating disordersF50.9 Eating disorder, unspeciﬁ  ed
F51 Non-organic sleep disorders
F51.0 Non-organic insomniaF51.1 Non-organic hypersomnia
F51.2 Non-organic disorder of the sleep-wake scheduleF51.3 Sleepwalking (somnambulism)F51.4 Sleep terrors (night terrors)
F51.5 Nightmares
F51.8 Other non-organic sleep disordersF51.9 Non-organic sleep disorder, unspeciﬁ  ed
F52 Sexual dysfunction, not caused by organic disorder or 
disease
F52.0 Lack or loss of sexual desire
F52.1 Sexual aversion and lack of sexual enjoyment
.10 Sexual aversion.11 Lack of sexual enjoyment

disease
F52.2 Failure of genital responseF52.3 Orgasmic dysfunctionF52.4 Premature ejaculationF52.5 Non-organic vaginismusF52.6 Non-organic dyspareuniaF52.7 Excessive sexual driveF52.8 Other sexual dysfunction, not caused by organic disorders or diseaseF52.9 Unspeciﬁ  ed sexual dysfunction, not caused by organic 
disorder or disease
F53 Mental and behavioural disorders associated with the 
puerperium, not elsewhere classiﬁ  ed
F53.0 Mild mental and behavioural disorders associated with the 
F53.1 Severe mental and behavioural disorders associated with the puerperium, not elsewhere classiﬁ  ed
F53.8 Other mental and behavioural disorders associated with the puerperium, not elsewhere classiﬁ  ed
F53.9 Puerperal mental disorder, unspeciﬁ  ed
F54 Psychological and behavioural factors associated with

F54 Psychological and behavioural factors associated with 
disorders or diseases classiﬁ  ed elsewhere
F55 Abuse of non-dependence-producing substances
F55.0 Antidepressants
F55.1 LaxativesF55.2 AnalgesicsF55.3 AntacidsF55.4 VitaminsF55.5 Steroids or hormonesF55.6 Speciﬁ  c herbal or folk remedies
F55.8 Other substances that do not produce dependenceF55.9 Unspeciﬁ  ed
F59 Unspeciﬁ  ed behavioural syndromes associated with 
physiological disturbances and physical factors
F60–F69 Disorders of adult personality and behaviour
F60 Speciﬁ  c personality disorders
F60.0 Paranoid personality disorderF60.1 Schizoid personality disorderF60.2 Dissocial personality disorderF60.3 Emotionally unstable personality disorder
.30 Impulsive type.31 Borderline type
F60.4 Histrionic personality disorderF60.5 Anankastic personality disorder1.9 diagnosis and classification

SECTION 1  the subject matter of and approach to psychiatry 112
F60.6 Anxious (avoidant) personality disorder
F60.7 Dependent personality disorderF60.8 Other speciﬁ  c personality disorders
F60.9 Personality disorder, unspeciﬁ  ed
F61 Mixed and other personality disorders
F61.0 Mixed personality disorders
F61.1 Troublesome personality changes
F62 Enduring personality changes, not attributable to brain 
damage and disease
F62.0 Enduring personality change after catastrophic experience
F62.1 Enduring personality change after psychiatric illnessF62.8 Other enduring personality changesF62.9 Enduring personality change, unspeciﬁ  ed
F63 Habit and impulse disorders
F63.0 Pathological gambling
F63.1 Pathological ﬁ  re-setting (pyromania)
F63.2 Pathological stealing (kleptomania)F63.3 TrichotillomaniaF63.8 Other habit and impulse disordersF63.9 Habit and impulse disorder, unspeciﬁ  ed
F64 Gender identity disorders
F64.0 Transsexualism

F64.1 Dual-role transvestismF64.2 Gender identity disorder of childhood
F64.8 Other gender identity disordersF64.9 Gender identity disorder, unspeciﬁ  ed
F65 Disorders of sexual preference
F65.0 Fetishism
F65.1 Fetishistic transvestismF65.2 ExhibitionismF65.3 VoyeurismF65.4 PaedophiliaF65.5 SadomasochismF65.6 Multiple disorders of sexual preferenceF65.8 Other disorders of sexual preferenceF65.9 Disorder of sexual preference, unspeciﬁ  ed
F66 Psychological and behavioural disorders associated with 
sexual development and orientation
F66.0 Sexual maturation disorder
F66.1 Egodystonic sexual orientation
F66.2 Sexual relationship disorder
F66.8 Other psychosexual development disordersF66.9 Psychosexual development disorder, unspeciﬁ  ed

A ﬁ fth character may be used to indicate association with:
.x0 Heterosexuality
.xl Homosexuality
.x2 Bisexuality
.x8 Other, including prepubertal
F68 Other disorders of adult personality and behaviour
F68.0 Elaboration of physical symptoms for psychological 
reasonsF68.1 Intentional production or feigning of symptoms or dis-abilities, either physical or psychological (factitious disorder)F68.8 Other speciﬁ  ed disorders of adult personality and behaviour
F69 Unspeciﬁ  ed disorder of adult personality and behaviourF70–F79 Mental retardation (intellectual disability)

F70 Mild mental retardation (intellectual disability)F71 Moderate mental retardation (intellectual disability)F72 Severe mental retardation (intellectual disability)F73 Profound mental retardation (intellectual disability)F78 Other mental retardation (intellectual disability)F79 Unspeciﬁ  ed mental retardation (intellectual disability)
A fourth character may be used to specify the extent of associated 
behavioural impairment:
F7x.0 No, or minimal, impairment of behaviourF7x.1 Signiﬁ  cant impairment of behaviour requiring attention 
or treatmentF7x.8 Other impairments of behaviourF7x.9 Without mention of impairment of behaviour
F80–F89 Disorders of psychological development
F80 speciﬁ  c developmental disorders of speech and language
F80.0 Speciﬁ  c speech articulation disorder

F80.1 Expressive language disorderF80.2 Receptive language disorderF80.3 Acquired aphasia with epilepsy (Landau-Kleffner syndrome)F80.8 Other developmental disorders of speech and languageF80.9 Developmental disorder of speech and language, unspeciﬁ  ed
F81 Speciﬁ  c developmental disorders of scholastic skills
F81.0 Speciﬁ  c reading disorder
F81.1 Speciﬁ  c spelling disorder
F81.2 Speciﬁ  c disorder of arithmetical skills
F81.3 Mixed disorder of scholastic skillsF81.8 Other developmental disorders of scholastic skillsF81.9 Developmental disorder of scholastic skills, unspeciﬁ  ed
F82 Speciﬁ  c developmental disorder of motor function
F83 Mixed speciﬁ  c developmental disorders
F84 Pervasive developmental disorders
F84.0 Childhood autism

F84.1 Atypical autismF84.2 Rett’s syndromeF84.3 Other childhood disintegrative disorderF84.4 Overactive disorder associated with mental retardation and stereotyped movementsF84.5 Asperger’s syndromeF84.8 Other pervasive developmental disordersF84.9 Pervasive developmental disorder, unspeciﬁ  ed
F88 Other disorders of psychological development
F89 Unspeciﬁ  ed disorder of psychological development
F90–F98 Behavioural and emotional disorders with onset 
usually occurring in childhood and adolescence
F90 Hyperkinetic disorders
F90.0 Disturbance of activity and attention
F90.1 Hyperkinetic conduct disorderF90.8 Other hyperkinetic disordersF90.9 Hyperkinetic disorder, unspeciﬁ  ed
F91 Conduct disorders
F91.0 Conduct disorder conﬁ  ned to the family context
F91.1 Unsocialized conduct disorder

113
F91.2 Socialized conduct disorder
F91.3 Oppositional deﬁ  ant disorder
F91.8 Other conduct disordersF91.9 Conduct disorder, unspeciﬁ  ed
F92 Mixed disorders of conduct and emotions
F92.0 Depressive conduct disorder
F92.8 Other mixed disorders of conduct and emotionsF92.9 Mixed disorder of conduct and emotions, unspeciﬁ  ed
F93 Emotional disorders with onset speciﬁ  c to childhood
F93.0 Separation anxiety disorder of childhood
F93.1 Phobic anxiety disorder of childhoodF93.2 Social anxiety disorder of childhoodF93.3 Sibling rivalry disorderF93.8 Other childhood emotional disordersF93.9 Childhood emotional disorder, unspeciﬁ  ed
F94 Disorders of social functioning with onset speciﬁ  c to 
childhood and adolescence
F94.0 Elective mutism
F94.1 Reactive attachment disorder of childhoodF94.2 Disinhibited attachment disorder of childhoodF94.8 Other childhood disorders of social functioningF94.9 Childhood disorders of social functioning, unspeciﬁ  ed
F95 Tic disorders

F95.0 Transient tic disorder
F95.1 Chronic motor or vocal tic disorderF95.2 Combined vocal and multiple motor tic disorder (de la T ourette’s syndrome)F95.8 Other tic disordersF95.9 Tic disorder, unspeciﬁ  ed
F98 Other behavioural and emotional disorders with onset 
F98.0 Non-organic enuresis
F98.1 Non-organic encopresisF98.2 Feeding disorder of infancy and childhoodF98.3 Pica of infancy and childhoodF98.4 Stereotyped movement disordersF98.5 Stuttering (stammering)F98.6 ClutteringF98.8 Other speciﬁ  ed behavioural and emotional disorders with 
onset usually occurring in childhood and adolescenceF98.9 Unspeciﬁ  ed behavioural and emotional disorders with 
onset usually occurring in childhood and adolescence
F99 Unspeciﬁ  ed mental disorder
F99 Mental disorder, not otherwise speciﬁ  ed
Appendix 2
Diagnostic and Statistical Manual of Mental 
Disorders (4th edition)
NOS = Not Otherwise Speciﬁ  ed.

Appendix 2
An x appearing in a diagnostic code indicates that a speciﬁ  c code 
number is required.
An ellipsis (. . .) is used in the names of certain disorders to indi-
cate that the name of a speciﬁ  c mental disorder or general medical condition should be inserted when recording the name (e.g., 293.0 
Delirium Due to Hypothyroidism).
If criteria are currently met, one of the following severity speci-
ﬁ ers may be noted after the diagnosis
MildModerateSevereIf criteria are no longer met, one of the following speciﬁ  ers may 
be noted
In Partial RemissionIn Full RemissionPrior History
Mental retardation
Note: These are coded on Axis II.
317 Mild Mental Retardation

318.0 Moderate Mental Retardation318.1 Severe Mental Retardation318.2 Profound Mental Retardation319 Mental Retardation, Severity Unspeciﬁ  ed
Learning disorders
315.00 Reading Disorder
315.1 Mathematics Disorder315.2 Disorder of Written Expression315.9 Learning Disorder NOS
Motor skills disorder
315.4 Developmental Coordination Disorder
Communication disorders
315.31 Expressive Language Disorder315.32 Mixed Receptive–Expressive Language Disorder315.39 Phonological Disorder307.0 Stuttering307.9 Communication Disorder NOS
Pervasive Developmental disorders
299.00 Autistic Disorder299.80 Rett’s Disorder299.10 Childhood Disintegrative Disorder299.80 Asperger’s Disorder299.80 Pervasive Developmental Disorder NOS
Attention-deﬁ  cit and disruptive behaviour disorders
314.xx Attention-Deﬁ  cit/Hyperactivity Disorder

.01 Combined Type.00 Predominantly Inattentive Type.01 Predominantly Hyperactive-Impulsive Type
314.9 Attention-Deﬁ  cit/Hyperactivity Disorder NOS
312.xx Conduct Disorder
.81 Childhood-Onset Type.82 Adolescent-Onset Type.89 Unspeciﬁ  ed Onset1.9 diagnosis and classification

SECTION 1  the subject matter of and approach to psychiatry 114
313.81 Oppositional-Deﬁ  ant Disorder
312.9 Disruptive Behaviour Disorder NOS
Feeding and eating disorders of infancy or early 
childhood
307.52 Pica
307.53 Rumination Disorder307.59 Feeding Disorder of Infancy or Early Childhood
Tic disorders
307.23 T ourette’s Disorder307.22 Chronic Motor or Vocal Tic Disorder307.21 Transient Tic DisorderSpecify if : Single Episode/Recurrent
307.20 Tic Disorder NOS
Elimination disorders
—.— Encopresis
787.6 With Constipation and Overﬂ  ow Incontinence
307.7 Without Constipation and Overﬂ  ow Incontinence
307.6 Enuresis (Not Due to a General Medical Condition)Specify type : Nocturnal Only/Diurnal Only/Nocturnal and 
Diurnal
Other disorders of infancy, childhood, or adolescence
309.21 Separation Anxiety DisorderSpecify if : Early Onset
313.23 Selective Mutism313.89 Reactive Attachment Disorder of Infancy or Early ChildhoodSpecify type : Inhibited Type/Disinhibited Type

307.3 Stereotypic Movement DisorderSpecify if : With Self-Injurious Behaviuor
313.9 Disorder of Infancy, Childhood, or Adolescence NOS
Delirium, dementia and amnestic and other 
cognitive disorders
Delirium
293.0 Delirium Due to . . . [Indicate the General Medical 
Condition]—.— Substance Intoxication Delirium (refer to Substance-
Related Disorders for substance-speciﬁ  c codes)
—.— Substance Withdrawal Delirium (refer to Substance-Related Disorders for substance-speciﬁ  c codes)
—.— Delirium Due to Multiple Etiologies (code each of the speciﬁ  c etiologies)
780.09 Delirium NOS
Dementia
294.xx Dementia of the Alzheimer’s Type, With Early Onset (also code 331.0 Alzheimer’s disease on Axis III)
.10 Without Behavioural Disturbance.11 With Behavioural Disturbance

Dementia
294.xx Dementia of the Alzheimer’s Type, With Late Onset (also code 331.0 Alzheimer’s disease on Axis III)
.10 Without Behavioural Disturbance.11 With Behavioural Disturbance290.xx Vascular Dementia
.40 Uncomplicated.41 With Delirium.42 With Delusions.43 With Depressed Mood
Specify if :With Behavioural Disturbance
Code presence or absence of a behavioural disturbance in the ﬁ  fth 
digit for Dementia Due to a General Medical Condition:
294.10 = Without Behavioural Disturbance
294.11 = With Behavioural Disturbance
294.1x Dementia Due to HIV Disease ( also code 042 HIV on Axis III )
294.1x Dementia Due to Head Trauma ( also code 854.00 head 
injury on Axis III )
294.1x Dementia Due to Parkinson’s Disease ( also code 331.82 
Dementia with Lewy Bodies on Axis III )

294.1x Dementia Due to Huntington’s Disease ( also code 333.4 
Huntington’s disease on Axis III )
294.1x Dementia Due to Pick’s Disease ( also code 331.11 Pick’s 
disease on Axis III )
294.1x Dementia Due to Creutzfeldt–Jakob Disease ( also code 
046.1 Creutzfeldt–Jakob disease on Axis III )
294.1x Dementia Due to . . . [ Indicate the General Medical 
Condition not listed above ] (also code the general medical 
condition on Axis III )
—.— Substance-Induced Persisting Dementia ( refer to Substance-
Related Disorders for substance-speciﬁ  c codes )
—.— Dementia Due to Multiple Etiologies ( code each of the 
speciﬁ  c etiologies )
294.8 Dementia NOS
Amnestic disorders
294.0 Amnestic Disorder Due to . . . [ Indicate the General Medical 
Condition ]
Specify if : Transient/Chronic

—.— Substance-Induced Persisting Amnestic Disorder ( refer to 
Substance-Related Disorders for substance-speciﬁ  c codes )
294.8 Amnestic Disorder NOS
Other cognitive disorder
294.9 Cognitive Disorder NOS
293.89 Catatonic Disorder Due to . . . [ Indicate the General 
Medical Condition ]
310.1 Personality Change Due to . . . [ Indicate the General Medical 
Specify type : Labile Type/Disinhibited Type/Aggressive Type/
Apathetic Type/Paranoid Type/Other Type/Combined Type/Unspeciﬁ  ed Type
293.9 Mental Disorder NOS Due to . . . [ Indicate the General 
The following speciﬁ  ers apply to Substance Dependence as noted:
aWith Physiological Dependence/Without Physiological 
Dependence

115
bEarly Full Remission/Early Partial Remission Sustained Full 
Remission/Sustained Partial Remission
cIn a Controlled Environment
dOn Agonist Therapy/
The following speciﬁ  ers apply to Substance-Induced Disorders 
as noted:
IWith Onset During Intoxication/WWith Onset During 
Withdrawal
Alcohol-related disorders
Alcohol use disorders
303.90 Alcohol Dependencea,b,c305.00 Alcohol Abuse
Alcohol-induced disorders
303.00 Alcohol Intoxication291.81 Alcohol WithdrawalSpecify if : With Perceptual Disturbances
291.0 Alcohol Intoxication Delirium291.0 Alcohol Withdrawal Delirium291.2 Alcohol-Induced Persisting Dementia291.1 Alcohol-Induced Persisting Amnestic Disorder291.x Alcohol-Induced Psychotic Disorder
.5 With Delusions
I,W
.3 With HallucinationsI,W
291.89 Alcohol-Induced Mood DisorderI,W
291.89 Alcohol-Induced Anxiety DisorderI,W
291.89 Alcohol-Induced Sexual DysfunctionI
291.82 Alcohol-Induced Sleep DisorderI,W
291.9 Alcohol-Related Disorder NOS

Amphetamine (or Amphetamine-like)-related 
disorders
Amphetamine use disorders
304.40 Amphetamine Dependencea,b,c
305.70 Amphetamine Abuse
Amphetamine-Induced Disorders
292.89 Amphetamine Intoxication
Specify if : With Perceptual Disturbances
292.0 Amphetamine Withdrawal292.81 Amphetamine Intoxication Delirium292.xx Amphetamine-Induced Psychotic Disorder
.11 With Delusions
I
.12 With HallucinationsI
292.84 Amphetamine-Induced Mood DisorderI,W
292.89 Amphetamine-Induced Anxiety DisorderI
292.89 Amphetamine-Induced Sexual DysfunctionI
292.85 Amphetamine-Induced Sleep DisorderI,W
292.9 Amphetamine-Related Disorder NOS
Caffeine-related disorders
Caffeine-induced disorders
305.90 Caffeine Intoxication292.89 Caffeine-Induced Anxiety Disorder
I
292.85 Caffeine-Induced Sleep DisorderI

I
292.9 Caffeine-Related Disorder NOSCannabis-related disorders
Cannabis use disorders
304.30 Cannabis Dependencea,b,c
305.20 Cannabis Abuse
Cannabis-induced disorders
292.89 Cannabis IntoxicationSpecify if : With Perceptual Disturbances
292.81 Cannabis Intoxication Delirium292.xx Cannabis-Induced Psychotic Disorder
I
292.89 Cannabis-Induced Anxiety DisorderI
292.9 Cannabis-Related Disorder NOS
Cocaine-related disorders
Cocaine use disorders
304.20 Cocaine Dependencea,b,c305.60 Cocaine Abuse
Cocaine-induced disorders
292.89 Cocaine IntoxicationSpecify if : With Perceptual Disturbances
292.0 Cocaine Withdrawal292.81 Cocaine Intoxication Delirium292.xx Cocaine-Induced Psychotic Disorder
I
292.84 Cocaine-Induced Mood DisorderI,W

I
292.89 Cocaine-Induced Anxiety DisorderI,W
292.89 Cocaine-Induced Sexual DysfunctionI
292.85 Cocaine-Induced Sleep DisorderI,W
292.9 Cocaine-Related Disorder NOS
Hallucinogen-related disorders
Hallucinogen use disorders
304.50 Hallucinogen Dependenceb,c
305.30 Hallucinogen Abuse
Hallucinogen-induced disorders
292.89 Hallucinogen Intoxication292.89 Hallucinogen Persisting Perception Disorder (Flashbacks)292.81 Hallucinogen Intoxication Delirium292.xx Hallucinogen-Induced Psychotic Disorder
I
292.84 Hallucinogen-Induced Mood DisorderI
292.89 Hallucinogen-Induced Anxiety DisorderI
292.9 Hallucinogen-Related Disorder NOS
Inhalant-related disorders
Inhalant use disorders
304.60 Inhalant Dependenceb,c
305.90 Inhalant Abuse
Inhalant-induced disorders

292.89 Inhalant Intoxication292.81 Inhalant Intoxication Delirium292.82 Inhalant-Induced Persisting Dementia1.9 diagnosis and classification

SECTION 1  the subject matter of and approach to psychiatry 116
292.xx Inhalant-Induced Psychotic Disorder
.11 With DelusionsI
292.84 Inhalant-Induced Mood DisorderI
292.89 Inhalant-Induced Anxiety DisorderI
292.9 Inhalant-Related Disorder NOS
Nicotine-related disorders
Nicotine use disorder
305.1 Nicotine Dependencea,b
Nicotine-induced disorders
292.0 Nicotine Withdrawal292.9 Nicotine-Related Disorder NOS
Opioid-related disorders
Opioid use disorders
304.00 Opioid Dependencea,b,c,d
305.50 Opioid Abuse
Opioid-induced disorders
292.89 Opioid IntoxicationSpecify if : With Perceptual Disturbances
292.0 Opioid Withdrawal292.81 Opioid Intoxication Delirium292.xx Opioid-Induced Psychotic Disorder
I
292.84 Opioid-Induced Mood DisorderI
292.89 Opioid-Induced Sexual DysfunctionI
292.85 Opioid-Induced Sleep DisorderI,W
292.9 Opioid-Related Disorder NOS
Phencyclidine (or Phencyclidine-like)-related disorders

Phencyclidine use disorders
304.60 Phencyclidine Dependenceb,c
305.90 Phencyclidine Abuse
Phencyclidine-induced disorders
292.89 Phencyclidine IntoxicationSpecify if : With Perceptual Disturbances
292.81 Phencyclidine Intoxication Delirium292.xx Phencyclidine-Induced Psychotic Disorder
I
292.84 Phencyclidine-Induced Mood DisorderI
292.89 Phencyclidine-Induced Anxiety DisorderI
292.9 Phencyclidine-Related Disorder NOS
Sedative-, Hypnotic-, Oranxiolytic-related disorders
Sedative, Hypnotic, or Anxiolytic use disorders
304.10 Sedative, Hypnotic, or Anxiolytic Dependencea,b,c
305.40 Sedative, Hypnotic, or Anxiolytic Abuse
Sedative-, Hypnotic-, or Anxiolytic-induced disorders

292.89 Sedative, Hypnotic, or Anxiolytic Intoxication292.0 Sedative, Hypnotic, or Anxiolytic WithdrawalSpecify it : With Perceptual Disturbances
292.81 Sedative, Hypnotic, or Anxiolytic Intoxication Delirium292.81 Sedative, Hypnotic, or Anxiolytic Withdrawal Delirium292.82 Sedative-, Hypnotic-, or Anxiolytic-Induced Persisting 
Dementia292.83 Sedative-, Hypnotic-, or Anxiolytic-Induced Persisting Amnestic Disorder292.xx Sedative-, Hypnotic-, or Anxiolytic-Induced Psychotic Disorder
I,W
.12 With HallucinationsI,W
292.84 Sedative-, Hypnotic-, or Anxiolytic-Induced Mood Disorder
I,W
292.89 Sedative-, Hypnotic-, or Anxiolytic-Induced Anxiety Disorder
W
292.89 Sedative-, Hypnotic-, or Anxiolytic-Induced Sexual Dysfunction
1
292.85 Sedative-, Hypnotic-, or Anxiolytic-Induced Sleep Disorder
I,W

W
1
I,W
292.9 Sedative-, Hypnotic-, or Anxiolytic-Related Disorder NOS
Polysubstance-related disorder
304.80 Polysubstance Dependencea,b,c,d
Other (or Unknown) substance-related disorders
Other (or Unknown) substance use disorders
304.90 Other (or Unknown) Substance Dependencea,b,c,d
305.90 Other (or Unknown) Substance Abuse
Other (or Unknown) substance-induced disorders
292.89 Other (or Unknown) Substance IntoxicationSpecify it : With Perceptual Disturbances
292.0 Other (or Unknown) Substance WithdrawalSpecify it : With Perceptual Disturbances
292.81 Other (or Unknown) Substance-Induced Delirium292.82 Other (or Unknown) Substance-Induced Persisting Dementia292.83 Other (or Unknown) Substance-Induced Persisting Amnestic Disorder292.xx Other (or Unknown) Substance-Induced Psychotic Disorder
I,W

I,W
292.84 Other (or Unknown) Substance-Induced Mood Disorder
I,W
292.89 Other (or Unknown) Substance-Induced Anxiety Disorder
I,W
292.89 Other (or Unknown) Substance-Induced Sexual Dysfunction
1
292.85 Other (or Unknown) Substance-Induced Sleep Disorder
I,W
292.9 Other (or Unknown) Substance-Related Disorder NOS
295.xx Schizophrenia
The following Classiﬁ  cation of Longitudinal Course applies to all subtypes of Schizophrenia .
Episodic With Interepisode Residual Symptoms ( specify if : With 
Prominent Negative Symptoms)/Episodic With No Interepisode Residual Symptoms/Continuous ( specify if : With Prominent 
Negative Symptoms)

117
Single Episode In Partial Remission ( specify if : With Prominent 
Negative Symptoms)/Single Episode In Full Remission
Other or Unspeciﬁ  ed Pattern
.30 Paranoid Type.10 Disorganized Type.20 Catatonic Type.90 Undifferentiated Type.60 Residual Type
295.40 Schizophreniform DisorderSpecify it : Without Good Prognostic Features/With Good 
Prognostic Features295.70 Schizoaffective DisorderSpecify type : Bipolar Type/Depressive Type
297.1 Delusional DisorderSpecify type : Erotomanic Type/Grandiose Type/Jealous Type/
Persecutory Type/Somatic Type/Mixed Type/Unspecified Type298.8 Brief Psychotic DisorderSpecify it : With Marked Stressor(s)/Without Marked Stressor(s)/
With Postpartum Onset297.3 Shared Psychotic Disorder293.xx Psychotic Disorder Due to . . . [Indicate the General Medical Condition]
.81 With Delusions.82 With Hallucinations
—.— Substance-Induced Psychotic Disorder (refer to Substance-Related Disorders for substance-speciﬁ  c codes)

Specify it : With Onset During Intoxication/With Onset During 
Withdrawal298.9 Psychotic Disorder NOS
Code current state of Major Depressive Disorder or Bipolar I 
Disorder in ﬁ  fth digit :
1= Mild
2= Moderate
3= Severe Without Psychotic Features
4= Severe With Psychotic Features
Specify : Mood-Congruent Psychotic Features/Mood-Incongruent 
Psychotic Features
5= In Partial Remission
6= In Full Remission
0= Unspeciﬁ  ed
The following speciﬁ  ers apply (for current or most recent episode) to 
Mood Disorders as noted
aSeverity/Psychotic/Remission Specifiers/bChronic/cWith 
Catatonic Features/dWith Melancholic Features/eWith Atypical 
Features/fWith Postpartum Onset
The following speciﬁ  ers apply to Mood Disorders as noted :
gWith or Without Full Interepisode Recovery/hWith Seasonal 
Pattern/iWith Rapid Cycling

Depressive disorders
296.xx Major Depressive Disorder,
.2x Single Episodea,b,c,d,e,f.3x Recurrenta,b,c,d,e,f,g,h
300.4 Dysthymic Disorder
Specify it : Early Onset/Late Onset Specify: With Atypical Features
311 Depressive Disorder NOS
Bipolar disorders
296.xx Bipolar I Disorder,
.0x Single Manic Episodea,c,f
Specify if : Mixed
.40 Most Recent Episode Hypomanicg,h,i
.4x Most Recent Episode Manica,c,f,g,h,i
.6x Most Recent Episode Mixeda,c,f,g,h,i
.5x Most Recent Episode Depresseda,b,c,d,e,f,g,h,i
.7 Most Recent Episode Unspeciﬁ  edg,h,i
296.89 Bipolar II Disordera,b,c,d,e,f,g,h,i
Specify (current or most recent episode) : Hypomanic/Depressed
301.13 Cyclothymic Disorder296.80 Bipolar Disorder NOS293.83 Mood Disorder Due to . . . [ Indicate the General Medical 

Specify type : With Depressive Features/With Major Depressive-
like Episode/With Manic Features/With Mixed Features—.— Substance-Induced Mood Disorder ( refer to Substance-
Specify type : With Depressive Features/With Manic Features/
With Mixed FeaturesSpecify if : With Onset During Intoxication/With Onset During 
296.90 Mood Disorder NOS
Anxiety Disorders
300.01 Panic Disorder Without Agoraphobia
300.21 Panic Disorder With Agoraphobia300.22 Agoraphobia Without History of Panic Disorder300.29 Speciﬁ  c Phobia
Specify type : Animal Type/Natural Environment Type/Blood-
Injection-Injury Type/Situational Type/Other Type300.23 Social PhobiaSpecify if : Generalized
300.3 Obsessive–Compulsive DisorderSpecify if : With Poor Insight

309.81 Posttraumatic Stress DisorderSpecify if : Acute/Chronic
Specify if : With Delayed Onset
308.3 Acute Stress Disorder
300.02 Generalized Anxiety Disorder
293.89 Anxiety Disorder Due to . . . [ Indicate the General Medical 
Specify if : With Generalized Anxiety/ With Panic Attacks/With 
Obsessive–Compulsive Symptoms—.— Substance-Induced Anxiety Disorder ( refer to Substance-
Obsessive–Compulsive Symptoms/With Phobic SymptomsSpecify if : With Onset During Intoxication/With Onset During 
Withdrawal300.00 Anxiety Disorder NOS
300.81 Somatization Disorder1.9 diagnosis and classification

SECTION 1  the subject matter of and approach to psychiatry 118
300.82 Undifferentiated Somatoform Disorder
300.11 Conversion DisorderSpecify type : With Motor Symptom or Deﬁ  cit/With Sensory 
Symptom or Deﬁ  cit/With Seizures or Convulsions/With Mixed 
Presentation307.xx Pain Disorder
.80 Associated With Psychological Factors.89 Associated With Both Psychological Factors and a General 
Medical ConditionSpecify if : Acute/Chronic
300.7 HypochondriasisSpecify if : With Poor Insight
300.7 Body Dysmorphic Disorder300.82 Somatoform Disorder NOS
300.xx Factitious Disorder
.16 With Predominantly Psychological signs and Symptoms.19 With Predominantly Physical Signs and Symptoms.19 With Combined Psychological and Physical Signs and Symptoms
300.19 Factitious Disorder NOS
300.12 Dissociative Amnesia300.13 Dissociative Fugue300.14 Dissociative Identity Disorder300.6 Depersonalization Disorder300.15 Dissociative Disorder NOS

Sexual dysfunctions
The following speciﬁ  ers apply to all primary Sexual Dysfunctions :
Lifelong Type/Acquired Type Generalized Type/Situational Type 
Due to Psychological Factors/Due to Combined Factors
Sexual desire disorders
302.71 Hypoactive Sexual Desire Disorder302.79 Sexual Aversion Disorder
Sexual arousal disorders
302.72 Female Sexual Arousal Disorder302.72 Male Erectile Disorder
Orgasmic disorders
302.73 Female Orgasmic Disorder302.74 Male Orgasmic Disorder
302.75 Premature Ejaculation
Sexual pain disorders
302.76 Dyspareunia (Not Due to a General Medical Condition)
306.51 Vaginismus (Not Due to a General Medical Condition)
Sexual dysfunction due to a general medical condition

625.8 Female Hypoactive Sexual Desire Disorder Due to . . . [Indicate the General Medical Condition ]608.89 Male Hypoactive Sexual Desire Disorder Due to . . . 
[Indicate the General Medical Condition ]
607.84 Male Erectile Disorder Due to . . . [ Indicate the General 
625.0 Female Dyspareunia Due to . . . [ Indicate the General 
608.89 Male Dyspareunia Due to . . . [ Indicate the General Medical 
625.8 Other Female Sexual Dysfunction Due to . . . [ Indicate the 
General Medical Condition ]
608.89 Other Male Sexual Dysfunction Due to . . . Indicate the 
—.— Substance-Induced Sexual Dysfunction ( refer to Substance-

Specify if : With Impaired Desire/With Impaired Arousal/With 
Impaired Orgasm/With Sexual PainSpecify if : With Onset During Intoxication
302.70 Sexual Dysfunction NOS
Paraphilias
302.4 Exhibitionism302.81 Fetishism302.89 Frotteurism302.2 PedophiliaSpecify if : Sexually Attracted to Males/Sexually Attracted to 
Females/Sexually Attracted to BothSpecify if : Limited to Incest
Specify type : Exclusive Type/Nonexclusive Type
302.83 Sexual Masochism302.84 Sexual Sadism302.3 Transvestic FetishismSpecify if : With Gender Dysphoria
302.82 Voyeurism302.9 Paraphilia NOS
Gender identity disorders
302.xx Gender Identity Disorder
.6 in Children.85 in Adolescents or Adults
Specify if : Sexually Attracted to Males/Sexually Attracted to 
Females/Sexually Attracted to Both/Sexually Attracted to Neither302.6 Gender Identity Disorder NOS302.9 Sexual Disorder NOS

307.1 Anorexia NervosaSpecify type : Restricting Type; Binge-Eating/Purging Type
307.51 Bulimia NervosaSpecify type : Purging Type/Nonpurging Type
307.50 Eating Disorder NOS
Primary sleep disorders
Dyssomnias
307.42 Primary Insomnia307.44 Primary HypersomniaSpecify if : Recurrent

119
347.00 Narcolepsy
780.57 Breathing-Related Sleep Disorder327.3X Circadian Rhythm Sleep Disorders   .31 Delayed Sleep Phase Type   .35 Jet Lag Type   .36 Shift Work Type   .30 Unspeciﬁ  ed Type
Type/Unspeciﬁ  ed Type
307.47 Dyssomnia NOS
Parasomnias
307.47 Nightmare Disorder307.46 Sleep T error Disorder307.46 Sleepwalking Disorder307.47 Parasomnia NOS
Sleep disorders related to another mental disorder
327.02 Insomnia Related to . . . [ Indicate the Axis I or Axis II 
Disorder ]
327.15 Hypersomnia Related to . . . [ Indicate the Axis I or Axis II 
Disorder ]
Other sleep disorders
780.xx Sleep Disorder Due to . . . [ Indicate the General Medical 
.52 Insomnia Type.54 Hypersomnia Type.59 Parasomnia Type.59 Mixed Type
—.— Substance-Induced Sleep Disorder ( refer to Substance-
Specify type : Insomnia Type/Hypersomnia Type/Parasomnia 
Type/ Mixed TypeSpecify if : With Onset During Intoxication/With Onset During 

Impulse control disorders not elsewhere 
classiﬁ  ed
312.34 Intermittent Explosive Disorder
312.32 Kleptomania312.33 Pyromania312.31 Pathological Gambling312.39 Trichotillomania312.30 Impulse-Control Disorder NOS
309.xx Adjustment Disorder
.0 With Depressed Mood.24 With Anxiety.28 With Mixed Anxiety and Depressed Mood.3 With Disturbance of Conduct.4 With Mixed Disturbance of Emotions and Conduct.9 Unspeciﬁ  ed
Specify if : Acute/Chronic
Note: These are coded on Axis II
301.0 Paranoid Personality Disorder301.20 Schizoid Personality Disorder

301.22 Schizotypal Personality Disorder301.7 Antisocial Personality Disorder301.83 Borderline Personality Disorder301.50 Histrionic Personality Disorder301.81 Narcissistic Personality Disorder301.82 Avoidant Personality Disorder301.6 Dependent Personality Disorder301.4 Obsessive–Compulsive Personality Disorder
301.9 Personality Disorder NOS
Other conditions that may be a focus of 
clinical attention
Psychological factors affecting medical condition
316 . . . [ Speciﬁ  ed Psychological Factor ]
Affecting . . . [ Indicate the General Medical Condition ]
Choose name based on nature of factors :
Mental Disorder Affecting Medical Condition
Psychological Symptoms Affecting Medical Condition
Personality Traits or Coping Style Affecting Medical Condition
Maladaptive Health Behaviours Affecting Medical Condition

Stress-Related Physiological Response Affecting Medical 
ConditionOther or Unspeciﬁ  ed Psychological Factors Affecting Medical 
Condition
Medication-induced movement disorders
332.1 Neuroleptic-Induced Parkinsonism333.92 Neuroleptic Malignant Syndrome333.7 Neuroleptic-Induced Acute Dystonia333.99 Neuroleptic-Induced Acute Akathisia333.82 Neuroleptic-Induced Tardive Dyskinesia333.1 Medication-Induced Postural Tremor333.90 Medication-Induced Movement Disorder NOS
Other medication-induced disorder
995.2 Adverse Effects of Medication NOS
Relational problems
V61.9 Relational Problem Related to a Mental Disorder or General Medical ConditionV61.20 Parent–Child Relational ProblemV61.10 Partner Relational ProblemV61.8 Sibling Relational ProblemV62.81 Relational Problem NOS
Problems related to abuse or neglect

V61.21 Physical Abuse of Child ( code 995.54 if focus of attention 
is on victim )
V61.21 Sexual Abuse of Child ( code 995.53 if focus of attention is 
on victim )
V61.21 Neglect of Child ( code 995.52 if focus of attention is on 
victim )
—.— Physical Abuse of AdultV61.12 (if by partner)V62.83 (if by person other than partner) ( code 995.83 if focus of 
attention is on victim )1.9 diagnosis and classification

SECTION 1  the subject matter of and approach to psychiatry 120
—.— Sexual Abuse of Adult
V61.12 (if by partner)V62.83 (if by person other than partner) ( code 995.83 if focus of 
attention is on victim )
Additional conditions that may be a focus of clinical 
attention
V15.81 Noncompliance With Treatment
V65.2 MalingeringV71.01 Adult Antisocial BehaviourV71.02 Child or Adolescent Antisocial BehaviourV62.89 Borderline Intellectual Functioning
Note: This is coded on Axis II
780.93 Age-Related Cognitive Decline
V62.82 BereavementV62.3 Academic ProblemV62.2 Occupational Problem313.82 Identity ProblemV62.89 Religious or Spiritual ProblemV62.4 Acculturation ProblemV62.89 Phase of Life Problem
Additional codes
300.9 Unspeciﬁ  ed Mental Disorder (nonpsychotic)
V71.09 No Diagnosis or Condition on Axis I
799.9 Diagnosis or Condition Deferred on Axis I
V71.09 No Diagnosis on Axis II
799.9 Diagnosis Deferred on Axis II
Acknowledgement

ICD-10 section of the chapter prepared by Michael B. First and Harold Alan Pincus is adapted from Delling’s original text. The contribution of the author to the original text is gratefully acknowledged.
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42. Helzer, J., Kraemer, H., Krueger, R., et al. (eds.) (2008). Dimensional 
Approaches in Diagnostic Classiﬁ  cation: Reﬁ  ning the Research Agenda for 
DSM-V .  American Psychiatric Association, Arlington, V A.
43. American Sleep Disorders Association. (2005). Diagnostic Classiﬁ  cation 
Steering Committee. International Classiﬁ  cation of Sleep Disorders: 
Diagnostic and Coding Manual.  American Academy of Sleep Medicine, 
Westchester, IL.
44. Andreasen, N., Olsen, S., Dennert, J., et al. (1982). Ventricular

44. Andreasen, N., Olsen, S., Dennert, J., et al. (1982). Ventricular 
enlargement in schizophrenia: relationship to positive and 
negative symptoms. American Journal of Psychiatry, 139, 
297–302.
45. Widiger, T., Simonsen, E., Krueger, R., et al.  (2005). Personality disorder 
research agenda for the DSM-V . Journal of Personality Disorder, 19(3), 
315–38.46. Helzer, J., Van den Brink, W. and Guth, S. (2006). Should there be both 
categorical and dimensional criteria for the substance use disorders in DSM-V . Addiction, 101(suppl. 1), 17–22.
47. Krueger, R., Watson, D. and Barlow, D. (2005). Introduction 
to the Special Section: toward a dimensionally-based taxonomy of psychopathology. Journal of Abnormal Psychology, 114,
491–3.
48. Cloninger, C. (1998). A new conceptual paradigm from genetics and 
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resolving the endophenotype. Behaviour and Research Therapy, 37(3), 
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50. Livesley, W. and Jang, K. (2000). T oward an empirically-based 
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1.10
From science to practice
The difﬁ  culties in keeping up to date
Clinicians need accurate and up-to-date information about emerg-
ing knowledge on assessment and treatment as well as other devel-
opments in practice. The presentation of this knowledge needs to 
be timely, accurate, and unbiased. In an ideal world, every psychia-
trist would have instantaneuous access to the original scientiﬁ  c 
articles. As this is not feasible because clinicians are busy and the 
skills needed for an adequate systematic search, critical appraisal, 
and interpretation of research articles are not routinely available. 
Further, the volume of research articles is staggering: about 2 mil-
lion papers are published in 20 000 biomedical journals every 
year,(1) and even if a psychiatrist restricted her reading to those 
clinical psychiatry journals it would be necessary to read about 
5500 papers each year—equivalent to 15 papers every day.(2)

Clearly, a strategy is required for efﬁ  cient and timely identiﬁ  cation 
of research that is both methodologically sound and clinically 
relevant.
Traditionally, clinicians have used a number of methods of keep-
ing up to date with research, including consulting colleagues and 
reading textbooks and journals. Smith(3) reviewed the research on 
the information needs of doctors and rated sources of information 
on several dimensions: their relevance to clinical practice, their sci-
entiﬁ  c validity, how easy they were to use, and an overall estimate 
of their usefulness. Most of the sources that scored highly on all 
dimensions (such as regularly updated evidence-based textbooks) 
were of limited availability. Traditional methods of obtaining infor-

mation (such as conventional textbooks and lecture-based con-
tinuing medical education) were more widely available, but of 
limited validity.
The difficulty in accessing reliable information means that 
many clinical decisions are made with a greater degree of uncer-
tainty than is necessary. The gap between research and clinical 
practice is often ﬁ  lled by an unsystematic combination of beliefs, 
opinions, and clinical experience, which inevitably leads to unnec-
essary variations in clinical practice. These have been widely 
documented in psychiatry and include variations in the use of elec-
troconvulsive therapy,(4,5) the use of antipsychotics,(6,7) and the 
treatment of depression.(8–10) The existence of these variations 
can only mean that some patients are not receiving the optimum 
treatment.Methods of improving use of best

treatment.Methods of improving use of best 
available evidence
A coherent set of strategies designed as a clinical tool to link the 
best available evidence directly to the care of individual patients 
was first formulated at McMaster University in Canada—an 
approach called evidence-based medicine .(11) Evidence-based 
medicine is problem-based and splits the process of linking research 
to practice into ﬁ  ve stages (Fig. 1.10.1) plus the identiﬁ  cation of 
clinical questions in need of more research.
T o make evidence-based practice feasible in real-life clinical 
practice, a number of problems need to be solved at each stage of 
the process.
Formulating a structured clinical question
When uncertainty arises in clinical practice, the clinician needs to 
formulate a structured clinical question. This step is fundamental

formulate a structured clinical question. This step is fundamental 
to the process of evidence-based medicine because it allows the 
Fig. 1.10.1 The ﬁ  ve stages of evidence-based medicine.

123
clinician ﬁ  rst to classify the question, second to identify the research 
architecture that is most likely to yield a reliable result, and ﬁ  nally 
to determine the most efﬁ  cient way of looking for the most reliable 
research.
(a) Example
Consider a patient who has suffered from two episodes of major depressive disorder both of which have caused substantial func-tional impairment. On each occasion his symptoms have respond-ed to treatment with a selective serotonin reuptake inhibitor. Following remission of symptoms, the patient has been advised to continue treatment for 6 months before gradually discontinuing the drugs. His psychiatrist is now considering whether or not to advise long-term treatment with antidepressant medication to reduce the risk of relapse. The patient wants to know the risk of relapse without treatment and how much this would be reduced by continuing the drugs. The process of rapidly ﬁ  nding the best answer 
begins by formulating a clinical question:

1 in patients with major depressive disorder who have responded 
to drug treatment (the problem )
2 how effective are antidepressants (the intervention )
3 compared with alternative treatments (including none) 
(the comparison intervention )
4 in preventing relapse (the outcome )?
The next step is to classify the question. This example clearly 
concerns a question about therapy. Most of the questions that arise in clinical practice concern therapy, diagnosis, prognosis, or aetiol-ogy. Once the question has been formulated and classiﬁ  ed, this 
suggests the most reliable research architecture (Table 1.10.1)
Finding evidence and advances in the organization of 
clinical knowledge
Identiﬁ  cation of the nature of the clinical question and the most 
reliable study design enables the clinician to do a focused and efﬁ  -

cient literature search. One of the main advances of evidence-based medicine has been the development of methods of research syn-thesis, or the process of identifying, appraising, and summarizing primary research studies into clinically usable knowledge. There are two main approaches to research synthesis—systematic reviews and clinical practice guidelines. Both these approaches are based on an explicit methodology that begins with the construction of a hierarchy of evidence in which certain forms of research architec-ture are considered to be reliable than others. The methodology is most clearly developed for questions about therapy and these will be the focus here.
(b) Levels of evidence
A commonly used hierarchy of evidence for studies of treatments is as follows:
Ia Evidence from a systematic review of randomized controlled

Ia Evidence from a systematic review of randomized controlled 
trials,
Ib Evidence from at least one randomized controlled trial,IIa Evidence from at least one controlled study without 
randomization,
IIb Evidence from at least one other type of quasi-experimental 
study,III Evidence from non-experimental descriptive studies, such as 
comparative studies, correlation studies, and case-control studies,
IV Evidence from expert committee reports or opinions and/or 
clinical experience of respected authorities.
In this hierarchy, randomized evidence is considered, on average, 
to be more reliable thsan non-randomized evidence, and a system-atic review of randomized evidence is considered to be the best defence against systematic bias.
Hierarchies of evidence have also been formulated for non-

therapeutic studies, such as studies of aetiology, diagnosis, and prognosis. Again, the fundamental feature of these hierarchies is that the study architectures with the least susceptibility to bias are considered most reliable. The study design considered most reliable for each type of clinical question is shown in Table 1.10.1.
(c) Systematic reviews
The need for systematic reviews and the methodology used are described in Chapter 6.1.1.2. The recognition of the need for sys-tematic reviews of randomized controlled trials, and the develop-ment of the scientiﬁ  c methodology of reviews, has been one of the 
most striking advances in health services research over the last decade. One key development was the founding of the Cochrane Collaboration, an international organization with the objective of Table  1.10.1  Types of clinical question and most reliable study 
architecture
Type of

Type of 
questionForm of the question Most reliable study architecture
Diagnosis How likely is a patient 
  who has a particular 
symptom, sign, or 
diagnostic test result to have a speciﬁ  c 
disorder?A cross-sectional study of patients 
  suspected of having the disorder 
comparing the proportion of the 
patients who really have the disorder who have a positive test result with 
the proportion of patients who do 
not have the disorder who have a positive test result.
Treatment Is the treatment of 
  interest more 
effective in producing a desired outcome than an alternative treatment (including no treatment)?Randomized evidence in which the 
  patients are randomly allocated 
to receive either the treatment of interest or the alternative: this is 
usually a systematic review of RCTs 
or a single high-quality RCT.
Prognosis What is the probability 
  of a speciﬁ  c 
outcome in this 
patient?A study in which an inception cohort 
  (patients at a common stage in

  (patients at a common stage in 
the development of the illness—
especially ﬁ  rst onset) are followed up 
for an adequate length of time.
Aetiology What has caused the 
 disorder?A study comparing the frequency of 
  an exposure in a group of persons 
with the disease (cases) of interest with a group of persons without 
the disease (controls)—this may be 
an RCT, a case-control study. or a cohort study.
RCT, randomized controlled trial.1.10 from science to practice

SECTION 1  the subject matter of and approach to psychiatry 124
producing regularly updated systematic reviews of the effectiveness 
of all health care interventions.(12)
(d) Clinical practice guidelines
In some areas of health care there is sufﬁ  cient evidence, coexisting 
with substantial clinical uncertainty, that it is worth developing clinical practice guidelines. Clinical practice guidelines have been deﬁ ned as ‘systematically developed statements to assist practitio-
ner decisions about appropriate health care for speciﬁ  c clinical cir-
cumstances’ .
(13) Guidelines have been developed for several years,

(13) Guidelines have been developed for several years, 
but there have been recent advances in the methodology of pro-ducing explicitly evidence-based guidelines. Evidence-based clini-cal practice guidelines are developed by a guideline development group consisting of key stakeholders who decide on the precise clinical questions to be answered. The evidence is then systemati-cally reviewed and classiﬁ  ed according to a hierarchy of evidence 
(see above) and presented to the guideline development group. The group then makes recommendations as appropriate. The degree to which the recommendations are directly based on the evidence is described using a second level of classiﬁ  cation
(14):
1 directly based on category I evidence;2 directly based on category II evidence or extrapolated 
recommendation from category I evidence;
3 directly based on category III evidence or extrapolated

3 directly based on category III evidence or extrapolated 
recommendation from category I or II evidence;
4 directly based on category IV evidence or extrapolated 
recommendation from category I, II, or III evidence.
Clinical practice guidelines are usually developed at a national 
level and need tailoring to suit local circumstances. Professional and scientiﬁ  c bodies such as the American Psychiatric Association 
and the British Association for Psychopharmacology often take the 
lead in developing national guidelines. Increasingly, health care 
providing organizations are developing clinical practice guidelines as a way of assuring quality, increasing standardization of care and

providing organizations are developing clinical practice guidelines as a way of assuring quality, increasing standardization of care and 
controlling costs. For example, in the United Kingdom, the National Institute for Health and Clinical Excellence (NICE) is now the main body producing guidelines across all disease areas. These guidelines are extremely rigorous in terms of methodology and also routinely include economic analyses of the cost-effectiveness of health care technologies. At their best, these guidelines produce the most accu-rate syntheses of current knowledge available. NICE also produces Health T echnology Appraisals (HTAs) of single interventions to determine the cost-effectiveness of new technologies (mainly medicines) prior to their introduction into the taxpayer-funded National Health Service. Cost-effectiveness analysis requires the translation of disease-speciﬁ  c estimates of clinical effectiveness

into the common metric of Quality Adjusted Life Y ears (QALYs) using sophisticated modelling techniques. Decisions about whether to allow reimbursement of the treatment depends on the cost per 
QALY (incremental cost-effectiveness ratio, ICER): a treatment 
with an ICER of more than £30 000 is unlikely to be approved. NICEs HTA decisions are particularly likely to be controversial when there is some evidence that the treatment works, but that the ICER is found to be too high—for example, in the case of acetyl-cholinesterase inhibitors in Alzheimer’s disease.
There are several limitations to clinical practice guidelines. 
Firstly, evidence-based clinical practice guidelines are expensive and time consuming to produce and rapidly become out of date. 
Secondly, to inﬂ  uence practice, evidence-based clinical practice 
guidelines need to be actively disseminated and implemented. Guidelines that are developed nationally and passively sent out to doctors are often not used.

(15) A number of active approaches are 
effective in helping change clinicians’ behaviour:(16)
◆ outreach visits (also known as academic detailing)
◆ local opinion leaders
◆ patient-mediated interventions (including patient education)
◆ multifaceted interventions involving a range of techniques.
There is some evidence that guidelines can improve patient out-
comes by their effect on clinical practice, especially when they are made relevant to local circumstances.
(15) In one study in the United 
States, 217 patients with depressive disorders were randomly assigned to usual care or a multifaceted intervention designed to achieve the Agency for Health Care Policy and Research guidelines on management of depression.
(17) Patients in the intervention

(17) Patients in the intervention 
group were much more likely to be treated in accordance with the guidelines, and this led to improved outcomes in patients with major depressive disorder (more than 50 per cent reduction on the Symptom Checklist-90 Depressive Symptom Scale at 4 months in 74 per cent of experimental patients compared with 44 per cent of control patients).
Understandably, clinicians also seek guidance in important 
clinical questions that are poorly served by high-quality, especially randomized, evidence. T o assist in these clinical decisions, Frances and his colleagues have developed an innovative method of guide-line development based on a systematic survey of the views of clinical experts.
(18,19)
(e) Use of electronic communication and the Internet

(18,19)
The development of the Internet—or World Wide Web—during the 1990s facilitated the development of evidence-based practice. The Internet has now become a vast information resource for doctors and patients. Improved access to information afforded to patients means that they are often very well informed about their condition. This is one of the factors contributing to the need for doctors to improve their own access to information. The Internet has several drawbacks including the disorganization of the information and the lack of quality control.
(20,21) Web portals have 
been developed that provide organized and indexed access to critically appraised websites (e.g. www.nelh.nhs.uk). The Web has now become the main medium for transmitting and storing knowledge.
(f) Improving current awareness

Another area of improvement has been the development of tools to assist doctors to maintain their current awareness of advances in research. The idea of review and abstracting journals is not new, but there has been a recognition that such journals also need a meth-odology to allow them to identify the most reliable and clinically important research studies.
A number of new journals have been produced with the aim of 
improving the availability of high-quality evidence to clinicians. The ﬁ  rst of these was ACP Journal Club  (targeted primarily at gen-
eral physicians), followed by Evidence-Based Medicine  (targeted 
primarily at family doctors) and, more recently, Evidence-Based Mental Health (aimed at mental health clinicians of all disciplines).

125
Evidence-Based Mental Health scans over 200 journals regularly 
and selects only those articles that both meet explicit methodologi-cal criteria (see Box 1.10.1) and are clinically important. The articles are then summarized in structured abstracts and published on one page with an accompanying commentary by a clinical expert.
A systematic approach to searching for the best 
The developments in the organization of clinical knowledge make 
it possible for a clinician to search rapidly and efﬁ  ciently for 
current best evidence using a standard approach (Fig. 1.10.2). This approach will change as new methods of organizing knowledge are developed.
(a) Example (continued)
Although a recent clinical guideline has been produced by NICE, it does not include sufﬁ  cient quantitative information to answer 
the patient’s question.
Geddes, J.R., Carney, S.M., Davies, C., Furukawa, T.A.,

Geddes, J.R., Carney, S.M., Davies, C., Furukawa, T.A., 
Kupfer, D.J., Frank, E., Goodwin. G.M. Relapse prevention with antidepressant drug treatment in depressive disorders. Lancet  2003, 
361: 653–61.
(22)
This is a systematic review of randomized controlled trials com-
paring a number of antidepressants (including tricyclics, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, and low-dose antipsychotics) with placebo in the prevention of relapse in depressive disorder.
Fig. 1.10.2 A systematic approach to identifying the best evidence about 
a therapy.
Box 1.10.1 Examples of the criteria for selection and review of 
articles for abstracting in Evidence-Based Mental Health
Articles are considered for abstracting if they meet the follow-
ing criteria
Basic criteria
◆ Original or review articles
◆ In English
◆ About humans
◆ About topics that are important to the practice of clinicians in 
the broad ﬁ  eld of mental health

Studies of prevention or treatment must meet these additional 
criteria
◆ Random allocation of participants to comparison groups
◆ Follow-up (endpoint assessment) of at least 80% of those 
entering the investigation
◆ Outcome measure of known or probable clinical importance
◆ Analysis consistent with study design
Studies of diagnosis must meet these additional criteria
◆ Clearly identiﬁ  ed comparison groups, at least one of which is 
free of the disorder or derangement of interest
◆ Interpretation of diagnostic standard without knowledge 
of test results
◆ Interpretation of test without knowledge of diagnostic 
standard result
◆ Diagnostic(gold) standard(e.g. diagnosis according to DSM-
IV or ICD-10 criteria after assessment by clinically qualiﬁ  ed

IV or ICD-10 criteria after assessment by clinically qualiﬁ  ed 
interviewer) preferably with documentation of reproducible criteria for subjectively interpreted diagnostic standard(e.g. report of statistically signiﬁ  cant measure of agreement among 
observers)
◆ Analysis consistent with study design.Studies of prognosis must meet additional criteria
◆ Inception cohort (ﬁ  rst onset or assembled at a uniform point 
in the development of the disease) of individuals, all initially free of the outcome of the interest
◆ Follow-up of at least 80% of patients until the occurrence of a 
major study endpoint
◆ Or to the end of the study
◆ Analysis consistent with study design.
Studies of causation must meet these additional criteria
◆ Clearly identiﬁ  ed comparison group for those at risk of, or

◆ Clearly identiﬁ  ed comparison group for those at risk of, or 
having, the outcome of interest (i.e. randomized controlled trial quasi-randomized controlled trial, non-randomized con-trolled trial, cohort analytical study with case by-case match-ing, or statistical adjustment to create comparable groups, case-control study)
◆ Masking of observers of outcomes to exposures (this criterion 
is assumed to be met if the outcome is objective), observers of exposures masked to outcomes for case-control studies, or masking of subjects to exposure for all other study designs
◆ Analysis consistent with study design.1.10 from science to practice

SECTION 1  the subject matter of and approach to psychiatry 126
Critical appraisal of research articles
Once the evidence has been found, it needs to be critically appraised 
for its reliability and usefulness. Psychiatrists need to be able to assess the scientiﬁ  c value and clinical importance of a study. This 
requires a range of epidemiological and biostatistical skills that have not traditionally been considered to be key skills for psychiatrists. In the United Kingdom, the Royal College of Psychiatrists intro-duced in 1999 a new part of the main professional examination that is designed to test these skills, recognizing their fundamental importance for clinical psychiatrists.
(23)
Structured critical appraisal is an active process that involves a

(23)
Structured critical appraisal is an active process that involves a 
systematic assessment of the key methodological aspects of the paper. In particular, critical appraisal focuses systematically on those aspects of the study methodology that are most likely to lead to unreliability of results. A number of checklists, designed to make the appraisal quicker and more systematic, have been produced for different research study designs.
(24) For example, the critical 
appraisal of a systematic review involves an assessment of those aspects of methodology described in Chapter 6.1.1.2. A commonly used checklist for systematic reviews is shown in Table 1.10.2.
Using the checklist, the review can be quickly critically appraised. It is a review of the efﬁ  cacy of antidepressant drugs in preventing

Using the checklist, the review can be quickly critically appraised. It is a review of the efﬁ  cacy of antidepressant drugs in preventing 
recurrence of depression in patients who responded to acute phase therapy with antidepressants and so appears relevant to the clinical question. The authors have only included randomized controlled trials, and this will make systematic error less likely and improve the reliability of the review. The literature search strategy is clearly documented and included electronic databases (Medline, Psyclit, Embase, Lilacs, and the Cochrane Library), hand searching of jour-nals, and correspondence with researchers active in the ﬁ  eld and 
drug companies. The quality of the randomized controlled trials was rated both from the description of the allocation of treatment and by assessing other methodological issues such as whether the primary analysis was done as an intention-to-treat analysis and the

degree of blinding of the clinician and patient. It can be concluded 
that the reviewers have made a reasonable effort to identify the pri-mary studies, although it is possible that other studies, perhaps with negative results, have not been published (publication bias, see Chapter 6.1.1.2).
The results of the primary studies are shown graphically as odds 
ratios (see Glossary) in Fig. 1.10.3. Odds ratios falling to the left of the vertical line indicate that the outcome (relapse of depressive symptoms) occurred less frequently in patients who continued treatment with an antidepressant. The smaller the odd ratio, the larger the treatment effect found in that particular study. For each study, the central diamond represents the most likely value of the relative risk and the box around the relative risk shows the 95 per cent conﬁ dence interval ( CI). The larger studies (e.g. **Rouillon et al.
(25))
have narrower conﬁ  dence intervals because they are larger and

(25))
have narrower conﬁ  dence intervals because they are larger and 
therefore have less random error and greater precision.
From the ﬁ  gure, it can be seen that, the odds ratio of the all 
the studies included fall on the left-hand side of the line and there-fore found the same direction of treatment effect. There is consid-erable overlap in the conﬁ  dence intervals from study to study and, 
although there is some statistically signiﬁ  cant hetero geneity between 
them (see Chapter 6.1.1.2), this appears to be in the size—rather than the nature—of the positive treatment effect. At the bottom of the ﬁ  gure is the estimate of the combined treatment effect of 
the trials. This is expressed as a pooled odds ratio. Combining the 
study results produces a more precise estimate of the drug’s relative effectiveness, with tighter conﬁ  dence intervals. The overall pooled 
odds ratio of relapse for patients taking antidepressants compared

odds ratio of relapse for patients taking antidepressants compared 
with placebo is 0.30 (95 per cent CI (see Glossary), 0.22–0.38).
Methods of using research ﬁ  ndings at the level of 
individual patients
After the study has been critically appraised for its validity, the 
clinician needs to determine what the results are, and their importance for the patient. Patients in research studies are always different from those in real-life clinical practice in ways that may be difﬁ  cult to determine even only if because they–or at least the Table 1.10.2  Checklist to assist the critical appraisal of a systematic 
review
Validity
1. Did the review address a clearly focused clinical question?
Did the review describe:
 the population studied?
 the intervention given?
 the outcomes considered?
2. Did the authors select the right sort of studies for the review?
The right studies would:
 address the review’s question have an adequate study design (e.g. for a question re therapy, an RCT)

3. Were the important relevant studies included in the review?
 Which bibliographic databases were used?
 Personal contact with experts Search for unpublished as well as published studies
 Search for non-English language studies
4. Did the review’s authors assess the quality of the included studies?
Did they use:
 description of randomization?
 a rating scale?
Results
5. Were the results similar from study to study?
 Are the results of all the included studies clearly displayed? Are the results from different studies similar?
 If not, are the reasons for variations between studies discussed?
6. What is the overall result of the review?
 Is there a clear clinical conclusion (a clinical bottom-line)? What is it?
 What is the numerical result?
7. How precise are the results?

 Is there a conﬁ  dence interval?
Clinical relevance of the results
8. Can I apply the results to my patient?
 Is this patient so different from those in the trial that the results do not   apply?
9. Should I apply the results to my patient?
 How great would the beneﬁ  t of therapy be for this particular patient? Is the intervention consistent with my patient’s values and preferences?
 Were all the clinically important outcomes considered?
 Are the beneﬁ  ts worth the harms and costs?
RCT, randomized controlled trial.

127
episode of illness–was in the past rather than the present. Therefore, 
the use of results from research studies in clinical practice should 
be cautious and always requires a degree of extrapolation. The con-
tribution of clinical epidemiology is in developing methods of 
applying research results to individual patients that are biologically 
and statistically robust and are explicit about any assumptions 
made. One of the most useful questions to ask when applying the 
results of a research study is: ‘Is my patient so different from those 
in the study that the results cannot be used’? The next step is to try 
to interpret the study results for a particular patient, in terms of his 
or her clinical characteristics and treatment preferences.
An alternative measure of treatment effect which many ﬁ  nd 
more clinically useful than the relative risk or odds ratio is the 
number needed to treat ( NNT ).(26,27)  The NNT is an estimate of

number needed to treat ( NNT ).(26,27)  The NNT is an estimate of 
the number of patients that would need to be treated with the 
intervention of interest, compared with the alternative, in order to 
achieve one good outcome or to avoid one harmful outcome. The 
NNT is calculated by taking the reciprocal of the difference between 
the rates of the outcome of interest in the experimental and control 
groups.
Although the review supports the general conclusion that contin-
ued therapy with the same antidepressant that was effective in acute 
phase therapy is very much likely to decrease the risk of relapse, a 
clinician may wish to check the evidence for a speciﬁ  c drug. For 
example, how strong is the evidence for reboxetine? The systematic 
review identiﬁ  es one trial that directly answers this question(28).

This was a multicentre trial performed in centres in Europe and 
South America. The trial recruited 358 outpatients who met DSM-
IIIR criteria for an acute recurrence of major depressive disorder 
to open-label reboxetine and randomized the 285 patients who 
achieved >50 per cent reduction in baseline depressive symptoms 
on the Hamilton Depression Rating Scale to either continued 
reboxetine or placebo (mean age reboxetine 43.4 years, placebo 
42.3 years, women 79.3 per cent reboxetine: 67.4 per cent men). One group of 145 patients were allocated to reboxetine, 4 mg b.d. 
and 141 patients were allocated to placebo. Treatment was contin-
ued for a further 46 weeks and the primary outcome was relapse 
(increase in the Hamilton Depression Rating Scale of 50 per cent or 
more and/or a total score of ≥18 points).

(i) Appraising the validity of a randomized controlled trial
The appraisal of an individual randomized controlled trial also 
addresses issues of internal and external validity. The main differ-
ence compared with the appraisal of a systematic review is that the 
reader can appraise the trial directly, rather than relying on the 
author of the review to have made an adequate assessment of 
the quality of the studies included. The most important questions 
to answer during the appraisal of the article are those relating to 
methodological issues that have been randomly shown to affect the 
reliability of the results (Table 1.10.3).
This study(28) was a randomized controlled trial . The method 
of randomization is not stated and no details are provided about

of randomization is not stated and no details are provided about 
the concealment of treatment allocation . Concealment of 
allocation is one of the most important features to appraise in 
a randomized controlled trial, and refers to how well the treatment 
allocation of the next patient was concealed from the participating 
clinician.(29) If a clinician has deﬁ  nite knowledge of, or can reason-
ably predict, the next allocation, he may decide not to enter a 
patient if he favours either treatment in that speciﬁ  c case. This 
would obviously lead to a subversion of randomization and biased 
results. This is why methods of quasi-randomization, such as alter-
nate allocation, are often unsatisfactory. The most satisfactory 
methods of random allocation are when allocation is performed by 
a third party following entry of the patient into the study, for

a third party following entry of the patient into the study, for 
example using a centralized telephone service. Concealment of 
allocation should be distinguished from blinding  of treatment 
allocation. Blinding refers to whether the patient ( single blind ), or 
both the patient and the clinician ( double blind ), are kept unaware 
of which arm of the study the patient has been allocated to follow-
ing randomization. Blinding protects against bias in the treatment 
during the trial and in the assessment of subjective outcomes, but 
can be difﬁ  cult to maintain when the experimental treatment 
has characteristic side-effects (e.g. antidepressants). This study 
was reported to be double blind; however, it is difﬁ  cult to tell how 
effective the blinding was and whether this affected the treatment 
that the patients received or the ratings of outcome.

Of the patients who were randomized, 79/145 (54 per cent) of 
those allocated to reboxetine and 65/141 (46 per cent) of those 
allocated to placebo completed the trial. The reasons for drop-out 
are clearly stated and all the patients who entered the study are 
accounted for. Patients who drop out of a study may be different 
from those who complete it—this is a particular problem if there 
Table 1.10.3  Questions that must be answered during the appraisal 
of an article
1. Was the assignment of the patients randomized?
2. Was the randomization list concealed?
3. Were all the subjects who entered the trial accounted for at its conclusion?
4. Were they analysed in the groups to which they were randomized?
5. Were subjects and clinicians ‘blind’ to which treatment was being received?

6. Other than the experimental treatment, were the groups treated equally?
7. Were the groups similar at the start of the trial?Fig. 1.10.3 Antidepressant versus placebo for the prevention of relapse in 
depressive disorder. (Reprinted from the Lancet , 361, Geddes, J.R., Carney, S.M., 
Davies, C., et al. (2003), Relapse prevention with antidepressant drug treatment in 
depressive disorders, 653–61 Copyright 2003, with permission from Elsevier).(22)
1.10 from science to practice

SECTION 1  the subject matter of and approach to psychiatry 128
isdifferential drop-out  between the arms of the study. For this 
reason, the most statistically reliable and clinically useful method of analysis is to include all patients who were randomized in the analysis. This is called an intention-to-treat analysis (ITT) . In the 
reboxetine trial
(28) the primary analysis was done on an ITT basis 
(although three patients who dropped out before the ﬁ  rst follow-

up assessment were excluded from the primary analysis—these were included in the systematic review), and the patients were ana-lysed in the groups to which they were randomized. Lastly, although randomization will avoid bias in treatment allocation, it is possible that, by chance, the groups will be unbalanced on some key prog-nostic factors such as age, sex, duration, and severity of illness. Therefore it is important to assess the baseline characteristics of the patients to identify any obvious differences. In Versiani et al.
(28)
the patients were reasonably similar on baseline characteristics 
at entry into the trial, although the proportion of females was a little higher in the reboxetine group.
(ii) Are the results relevant for your patient?

T o determine the relevance of the study to real-life patients, it is important to examine the inclusion and exclusion criteria of the trial. The main inclusion criteria are discussed above. Patients excluded from the trial were those with coexisting psychotic fea-tures or chronic depression, those with a ﬁ  rst episode at the time of 
screening and patients with a history of seizures, serious brain injury, clinically signiﬁ  cant haemopoietic or cardiovascular disease, 
urinary retention, or glaucoma. The user of the study results will have to take these inclusion and exclusion criteria into account, and the clinician needs to judge the relevance of the results for the individual patient.
(iii) What are the results?

Of the 145 patients treated with reboxetine, 29 relapsed, giving an experimental event rate ( EER ), of 20 per cent or a probability 
of relapse of 0.2. In the placebo-treated group 73 of 141 patients relapsed giving a control event rate ( CER ) of 52 per cent. Therefore 
the absolute difference between the rates was
 EER − CER = 32 per cent
and the difference between the probabilities is 0.32. This means 
that for every 100 patients treated with reboxetine, compared with placebo, 32 fewer relapsed. Therefore, to prevent one relapse over 46 weeks, 100/32, or about three patients, would need to be treated (NNT) with reboxetine.
(b) Interpretation of numbers needed to treat
The clinical interpretation of NNT depends on the seriousness of the outcome and the nature (and cost) of the intervention.
For example, if the number needed to treat with aspirin following

For example, if the number needed to treat with aspirin following 
acute stroke to avoid one death in the short-term is 100, this seems a very useful intervention because death is such a serious outcome that it is worth treating a lot of patients to save a few from dying—especially as aspirin is very cheap. Some examples of NNTs are given in Table 1.10.4.
Critical appraisal of other research designs
The approach taken to the appraisal of research designs applied to other clinical questions is similar to that outlined above. Rather than passively reading the article or abstract, the clinician actively searches out the most important methodological features to

determine the reliability of the study. By applying the methods developed by clinical epidemiologists, the results presented in the paper can be used to calculate more clinically meaningful measures. These can, in turn, be tailored to suit the characteristics of the individual patient. The clinician needs to develop a practical knowledge of the tools to allow him to use them routinely and quickly in clinical practice and also to develop sufﬁ  cient familiarity 
to be able describe the results of studies to colleagues and patients.
Glossary
◆Absolute risk reduction (risk difference)  is the absolute 
arithmetic difference in the risk of the adverse outcome between control group (CER) and experimental group (EER). When an intervention increases the probability of a beneﬁ  cial outcome it 
is known as the absolute beneﬁ  t increase (ABI).
◆Conﬁ  dence interval (CI)  is the range within which the true value

◆Conﬁ  dence interval (CI)  is the range within which the true value 
of a statistical measure can be expected to lie. The CI is usually accompanied by a percentage value (usually 95 per cent) which shows the level of conﬁ  dence that the true value lies within this 
range.
◆Event rate  is the proportion of patients in a group in whom the 
event is observed. In control patients, this is called the control event rate (CER) and in experimental patients it is called the experimental event rate (EER). The patient expected event rate (PEER) refers to the rate of events that would be expected in a patient who received no treatment or conventional treatment.
◆Number needed to treat (NNT)  is the reciprocal of the absolute 
risk reduction and is the number of patients that need to be treated to prevent one bad outcome or to achieve one beneﬁ  cial 
outcome.
◆Odds ratio  is the odds of the outcome in the experimental group

outcome.
◆Odds ratio  is the odds of the outcome in the experimental group 
divided by the odds of the outcome in the control group. The odds ratio is often reported in meta-analyses because of its useful statistical properties.
◆Relative risk  is the risk of the outcome in the experimental group 
divide by the risk of the outcome in the control group. The risk ratio is increasingly reported in meta-analyses because it is easier to interpret clinically than the odds ratio.Table 1.10.4  Examples of numbers needed to treat for interventions 
in psychiatry assessment and report
Intervention Outcome NNT 95% Cl Reference
Cognitive therapy in 
bulimia nervosaLong-term 
remission23 0
Antidepressants in 
dysthymic disorderClinical response 5 3–10 31
Family therapy in 
schizophreniaRelapse at 1 year 7 4–14 32
SSRIs compared with 
TCAs in depressive 
disorderRemain in 
treatment at 
6 weeks39 20–426 28
SSRI, selective serotonin reuptake inhibitor, TCA tricyclic antidepressant.

129
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310, 1433–8.1.10 from science to practice

2.1 Brain and mind  133
†R. C. A. Pearson
  2.3.7 Structural magnetic resonance imaging  191
201
Robert Dantzer and Keith W. Kelley 2.4 The contribution of genetics  212

 2.5.1 Development psychology through infancy, childhood, and adolescence   
234
R. J. Dolan
 2.5.5 Neuropsychological basis of neuropsychiatry  262
 2.6.2 Social and cultural anthropology: 
salience for psychiatry  275
Scott HendersonSECTION 2
The Scientiﬁ  c Basis of

The Scientiﬁ  c Basis of 
Psychiatric Aetiology

2.1
Brain and mind
History of the mind–brain relation
The thesis that the brain, rather than the heart, is the seat of the 
mind was already widely accepted by the ancient Greeks; but it was not universally accepted—Aristotle was an exception. Many issues in psychiatry resonate with the ancient debates over the roles of the heart and the brain. But a brief review of modern thinking about the mind–brain relation can begin two millennia later with René Descartes, who held that minds are real things of a fundamentally different kind from material bodies.
(1)
Dualism: Descartes
Descartes’s world-view included bodies or material things, whose essence is to be extended in space, and minds, which are immaterial things whose essence is thinking. According to Cartesian dualism ,

the mind is not literally housed within the body, because spatial properties belong to matter and not to mind. But, when he talked about the way we experience the states of our own body, Descartes sometimes spoke of the mind being ‘mixed up with’ the body.
Early theories of the brain as the seat of the mind assigned an 
important role to the ventricles. On Descartes’s view, mechanical operations involving the release of animal spirits in the ventricles were adequate to explain animal behaviour but intelligent human action required something more. He postulated that the immate-rial mind could modulate processes in the material brain by way of 
a causal interaction operating through the pineal gland.
The motion of bodies and the completeness of physics

Dualist interactionism  is challenged by theories about the motion 
of bodies. According to Descartes’s own theory, quantity of motion (deﬁ ned as mass times speed) is conserved. Because motion is not a 
directional notion, this conservation law allowed that the immate-rial mind could bend the trajectory of a physical particle in the pinealgland. But Gottfried Leibniz’s superior theory, with conservation laws for momentum (a directional notion) and kinetic energy, had the consequence that only impacts with other bodies could cause changes in the direction or speed of physical particles. This left no room for immaterial causes of material changes and, while Leibniz was a dualist, he was not an interactionist dualist but believed, instead, in a pre-established harmony  between the material and 
immaterial worlds.By departing from the idea that impact was the only force on

immaterial worlds.By departing from the idea that impact was the only force on 
bodies, and allowing action at a distance, Isaac Newton reopened the possibility of distinctively mental forces affecting the trajectory of bodies. These forces were not even ruled out by the law of con-servation of energy, which was widely accepted by the middle of the nineteenth century, but advances in biochemistry and neuro-physiology during the ﬁ  rst half of the twentieth century made 
appeal to vital and mental forces seem increasingly unmotivated. Since around 1950, the dominant theories of the mind–brain rela-tion have been compatible with a broadly physicalist world-view and with the completeness of physics: physical effects have wholly physical causes.
(2)
Behaviourism: Ryle

(2)
From the 1920s to the 1950s, particularly in the United States, behaviourism was a dominant approach within psychology. This was not just methodological behaviourism, which is a restriction on the kinds of evidence that can be used, but a radical reconcep-tion of psychology as the science of behaviour rather than the science of the mind. In philosophy, analytical behaviourism  was a 
doctrine about the meaning of our mental discourse. The idea was to analyse or translate our mental talk into talk about patterns of behaviour.
Gilbert Ryle promoted behaviourism as a response to what he 
called ‘Descartes’s myth’ of ‘the ghost in the machine’ .
(3) A dualist

(3) A dualist 
would regard talk about being in love, or wanting to visit Paris, as talk about an immaterial mind whose states lie hidden behind observable bodily behaviour. Ryle proposed to analyse this mental talk as being about the observable behaviour itself. He did not, however, aim to replace all mental terms by terms appropriate to the science of material bodies moving through space. He analysed 
believing that the ice is thin as, in part, being ‘prone to skate warily’ 
and it was enough, for his purposes, that skating warily is an observ-
able and recognizable kind of behaviour, even if it is not readily 
deﬁ ned in terms of the trajectories of body parts.
Because action is explained in terms of what the agent believes 
and what the agent wants, analytical behaviourism faces a major

and what the agent wants, analytical behaviourism faces a major 
objection of principle. There is no pattern of behaviour associated with a belief, by itself. Someone who believes that the ice is thin but has an unusual desire to be immersed in ice-cold water may not skate warily. So there is no prospect of analysing any belief in terms

134
of behaviour. We might elevate this point into a general requirement 
on the description of any creature as having beliefs. Attributions of beliefs are not warranted if they merely summarize the creature’s dispositions to exhibit patterns of behaviour. A belief is a mental state that can ﬁ  gure in the explanation of indeﬁ  nitely many differ-
ent actions in pursuit of different goals.
The identity theory: Place and Smart
Ryle’s behaviourism involved a clear rejection of Descartes’s duality of material and immaterial substances, but central state materialism
(also known as the identity theory ) encapsulated a more thorough-
going commitment to the physicalist world-view. If the physical effects of our experiences, thoughts, and volitions have wholly physical causes then there is no causal work left for distinct mental items to do. T o avoid epiphenomenalism, mental states, processes and events were to be identiﬁ  ed with physical states, processes and

events, and mental properties with physical properties. Place advanced a precursor of the identity theory, restricted to the case of conscious experiences,
(4) and this was generalized by Smart, 
who identiﬁ  ed beliefs and desires, intentions and hopes, as well as 
sensations and experiences, with brain states or processes.(5)
The identity theory defends the idea of mental causation  by 
identifying each mental state with a physical state that is a locus of causal powers. But, taken literally, the identity theory is bound to seem chauvinistic. No being with a physical constitution radically different from ours could be described as feeling anything, or thinking anything, or wanting anything.
Functionalism: Putnam and Lewis

The functionalist response to the identity theory is that what a system does is more important than what it is made from. Physically different computing machines can run the same software and one version of the functionalist theory of the mind–brain relation is that the mind is the software of the brain.
(6)
In an early version of functionalism , Hilary Putnam proposed 
that mental states are functional states like the states of an abstractly deﬁ ned Turing machine rather than physical states like the states of 
a human brain.
(7) This machine functionalism  had the advantage 
of not tying mental states to a particular physical substrate but also a disadvantage. Since a Turing machine is in only one state at a time, machine states are not analogous to mental states like being in love or wanting to visit Paris.
The dominant version of contemporary functionalism, attribut-
able to David Lewis, is analytical functionalism .
(8) The leading idea

(8) The leading idea 
is that commonsense speciﬁ  cations of the interconnected causal 
roles of mental states can be taken as interlocking analyses of mental state terms. For any physical being with a mind, there will be physi-cal states playing each of the mental state causal roles but different physical states may play the same causal role in physically different minded beings—in human beings and Martians, for example.
Functionalism thus avoids the apparent chauvinism of the iden-
tity theory by allowing that a human being may be in the same mental state as a being with a very different physical constitution. But functionalism faces the opposite problem of apparently being too liberal. It seems to be possible to make up examples in which physical states play the causal roles that are supposed to deﬁ  ne

mental states, yet where, intuitively, there is no intelligence and no mental life.
(9)Challenges to functionalism
The dominant contemporary theories of the mind–brain relation are compatible with a broadly physicalist world-view and analytical functionalism, in particular, is consistent with a version of physi-calism, a priori physicalism , that is both ontologically and concep-
tually reductionist .
(10)
Ontologically , analytical functionalism is like the identity theory 
in its commitment to types of physical state that realize  mental 
states. Functionalism does not quite say that being in pain is to be identiﬁ  ed with having C-ﬁ  bres ﬁ  ring (the standard example for the 
identity theory); but it does say that the causal role of the mental state of being in pain is played, in human beings, by the physical state of having C-ﬁ  bres ﬁ  ring.
Despite this ontological similarity to the identity the ory, analytical

Despite this ontological similarity to the identity the ory, analytical 
functionalism is conceptually  more like analytical behaviourism in 
being a thesis about the meanings of our mental terms. According to behaviourism, it is a matter of meaning, or conceptual analysis ,
that being in a mental state is being disposed to produce particular patterns of behaviour. According to functionalism, it is equally a matter of meaning that being in a mental state is being in a state 
that plays a particular causal role. Consequently, analytical func-
tionalism is conceptually reductionist . The mental facts, as conceived 
by the functionalist, are entailed a priori  by the physical facts.
As we shall now see, both the ontological and the conceptual 
commitments of analytical functionalism face challenges.
Rylean behaviourism revisited
A theorist of the mind–brain relation who was sympathetic to Rylean behaviourism might challenge the ontological  commitments

A theorist of the mind–brain relation who was sympathetic to Rylean behaviourism might challenge the ontological  commitments 
that are shared by functionalism and the identity theory. The neo-behaviourist might accept the idea that if a system has a disposition to exhibit a particular pattern of behaviour then there must be a basis for this disposition in the system’s inner constitution. But he might argue that identifying individual mental states with physical states, or insisting that mental states are individually realized by physical states, goes beyond what is required by this idea.
Dispositions do not ﬂ  oat free of inner constitution and the 
behavioural dispositions of human beings are, presumably, under-pinned by states and processes of the brain. But it is not obviously required that there must be a single brain state that underpins precisely the dispositions that are associated with the attribution of

a single mental state. This neo-behaviourism may draw support 
from remarks made by Wittgenstein.
(11)
Neo-behaviourism will be open to objection so long as it retains 
the unattainable commitment to an analysis of belief attributions in behavioural terms. But there is an alternative view that abandons those analytical ambitions. The interpretationist  says that mental-
istic interpretation is answerable to a creature’s behaviour in various actual and hypothetical circumstances, but that this answerability is a matter of ‘making sense’ of the creature and cannot be codiﬁ  ed 
mental state by mental state.
(12) Rather, the interpreter casts a net

(12) Rather, the interpreter casts a net 
of psychological description—‘X is in pain; X is in love; X wants to visit Paris; X believes that the ice is thin; …’—over a writhing mass of behaviour. Tracts of human behaviour normally support this interpretive project and, presumably, the behaviour is susceptible of causal explanation. But we should not assume that the physical causes of behaviour must have an articulation that matches the structure of the interpreter’s description.
(13)SECTION 2  the scientific basis of psychiatric aetiology

135
Interpretationism is compatible with a broadly physicalist world-
view but it involves some departure from apparently plausible claims about mental reality and mental causation. The interpreta-tionist is not committed to the claim that there are individual men tal 
states—for example, individual beliefs such as my belief that there is a bottle of white wine in the refrigerator, or that I have an appointment at 9 a.m.—that are bearers of causal powers.
Consciousness and the explanatory gap
The conceptual  commitments of analytical functionalism are 
challenged by our conception of conscious mental states .
According to functionalism, all mental states are realized by physi-
cal, speciﬁ  cally neural, states and the phenomenal properties of con-

scious mental states are physical properties of those neural states. We can ask what makes the difference between conscious mental states and unconscious mental states. Is there, for example, something dis-tinctive about the neural underpinnings of conscious mental states? If we had a plausible answer to that question, there would be the further question why mental states with that dis tinctive neural nature 
are conscious  mental states. This question is apt to seem puzzling and 
even unanswerable. But, according to analytical functionalism, there would be no puzzling ‘why?’ question about consciousness. All the 
mental facts, including the facts about consciousness and 
phenomenology, are entailed a priori by the physical facts.
A powerful intuition thus speaks against the conceptual

A powerful intuition thus speaks against the conceptual 
commitments of analytical functionalism. For it seems that even the full physical story about the world would not settle a priori the question whether a creature was in a conscious mental state. It seems to be conceivable (not ruled out a priori) that there could be a creature physically just like one of us yet lacking consciousness—a zombie —or even a complete physical duplicate of our world from 
which consciousness was totally absent—a zombie world .
(14)
Between the physical sciences and the facts of consciousness there 
seems to be an explanatory gap .(15)
Thomas Nagel has drawn attention to a difference between two 
kinds of conception. Conceptions of conscious mental states are subjective ; they are accessible from some, but not all, points of

kinds of conception. Conceptions of conscious mental states are subjective ; they are accessible from some, but not all, points of 
view. The conscious mental states that we can conceive  are limited 
to relatively modest imaginative extensions from the conscious mental states that we ourselves undergo . In contrast, the conceptions 
deployed in grasping theories in the physical sciences are objective ;
they are accessible from many different points of view. The physical theories that we can grasp are limited, not by our sensory experience, but by our intellectual powers.
(16) Many contemporary philoso-
phers of consciousness argue that the explanatory gap is a product of this duality of conceptions. There is no a priori entailment from the physical and functional facts objectively conceived  to the 
phenomenal facts subjectively conceived .
The majority of these philosophers maintain that a duality of

The majority of these philosophers maintain that a duality of 
conceptions does not require an ontological dualism of substances, states, or properties and that the explanatory gap is consistent with physicalism as an ontological doctrine. But there is an impor-tant minority view that acceptance of an explanatory gap must lead to a rejection of physicalism. David Chalmers, beginning from the intuition of an explanatory gap, recommends a return to some form of dualism.
(17) Others argue in the opposite direction, 
embracing physicalism, denying that there is an explanatory gap, and accepting the counterintuitive conceptual reductionism of analytical functionalism.Personal and subpersonal levels of 
description and explanation
The mind–brain relation is an aspect of a more encompassing rela-
tionship between persons and the physical systems of which they are constituted, including systems of neural information processing.

tionship between persons and the physical systems of which they are constituted, including systems of neural information processing. 
Our conception of persons as such is a conception of subjects 
and agents. At the personal level of description and explanation, we describe what people feel, think, want and do, and we explain what people do in terms of their sensations, beliefs, and desires. As the case of conscious mental states illustrates, our personal-level 
descriptions  are not always entailed a priori by physical and func-
tional descriptions of the systems that constitute us. Personal-level descriptions involve subjective and normative concepts that are different from the objective and descriptive concepts that ﬁ  gure in 
the physical sciences.
Our personal-level explanatory practices  seem to be different in 
kind from our scientiﬁ  c practices of explaining the operation of

kind from our scientiﬁ  c practices of explaining the operation of 
mechanical systems. McDowell describes personal-level explana-tions as ‘explanations in which things are made intelligible by being revealed to be, or to approximate to being, as they rationally ought to be’ .
(18) In a similar spirit, Dennett describes them as ‘non-
mechanistic’ . A mechanistic account of what happens when a per-son feels, thinks, wants, and acts would belong at a quite different level of description and explanation, not the ‘level of people and their sensations and activities’ , but ‘the subpersonal  level of brains 
and events in the nervous system’ .
(19)
One extreme view of the relationship between the personal and

(19)
One extreme view of the relationship between the personal and 
subpersonal levels highlights what is distinctive about the personal level and regards it as substantially independent from the subpersonal level. This view might encourage the interpretationist account of per-sonal-level psychological descriptions, minimizing the ontological and causal commitments of personal-level discourse to avoid con-straints on that discourse from the subpersonal level of neuroscience.
The opposite extreme view is the conceptually reductionist view 
of analytical functionalism. The personal level is the level of mental states whose causal roles are revealed by conceptual analysis while the subpersonal level is the level of neural states that play those roles. There are no explanatory gaps. All that is true at the personal level is entailed a priori by physical truths at the subpersonal level.
According to an attractive view that is intermediate between

According to an attractive view that is intermediate between 
these two extremes, the relationship between the personal and 
subpersonal levels is one of interaction without reduction .
(20)
As against the ﬁ  rst extreme view, the personal level is not indepen-
dent of the subpersonal level but constrained by it, because our 
personal-level descriptions—cast in terms of experience, thought, 
planning, and agency—carry commitments about causal structure 
in the brain. But, as against the second extreme view, there are also explanatory gaps that reveal themselves when we try to construct illuminating accounts of those personal-level notions using only the subpersonal-level resources of neuroscience.
Descartes’s ontological dualism of mind and body made it difﬁ  cult 
for him to describe the phenomenology of embodiment, the way we experience our own body. Contemporary theories of the mind–

brain relation are predominantly physicalist, rather than dualist, in their ontology. But the duality of objective and subjective conceptions 2.1 brain and mind

SECTION 2  the scientific basis of psychiatric aetiology 136
still presents a challenge for the sciences of the mind. Persons 
understood as such, partly from the ﬁ  rst-person perspective—
persons conceived as subjects and agents, with their experiences, thoughts, plans and actions—will not be visible in a purely objective, scientiﬁ  c story of the physical world.
Anthology
Chalmers, D.J. (ed.) (2002). Philosophy of mind: classical and contemporary 
readings . Oxford University Press, Oxford.
Textbook
Braddon-Mitchell, D. and Jackson, F.C. (2007). Philosophy of mind and 
cognition: an introduction  (2nd edn). Blackwell Publishing, Oxford.
1. Descartes, R. (1641). Meditations on ﬁ  rst philosophy  In Descartes, R. 
(1988). Selected philosophical writings  (trans. eds. J. Cottingham, 
R. Stoothoff, and D. Murdoch). Cambridge University Press, Cambridge, UK.
2. Papineau, D. (2002). Thinking about consciousness , Appendix. Oxford 
University Press, Oxford.

3. Ryle, G. (1949). Descartes’ myth. In The concept of mind , Chap. 1. 
Penguin Books, Harmondsworth.
4. Place, U.T. (1956). Is consciousness a brain process? The British Journal 
of Psychology ,47, 44–50.
5. Smart, J.C.C. (1959). Sensations and brain processes. Philosophical 
Review ,68, 141–56.
6. Block, N. (1995). The mind as the software of the brain. In 
An invitation to cognitive science  (2nd edn), Vol. 3 (eds. E.E. Smith 
and D.N. Osherson), pp. 377–425. MIT Press, Cambridge, MA.
7. Putnam, H. (1967). The nature of mental states. Originally titled 
‘Psychological predicates’ . In Art, mind, and religion  (eds. W.H. Capitan 
and D.D. Merrill), pp. 37–48. University of Pittsburgh Press, 
Pittsburgh, PA. 8. Lewis, D. (1972). Psychophysical and theoretical identiﬁ  cations.

Pittsburgh, PA. 8. Lewis, D. (1972). Psychophysical and theoretical identiﬁ  cations. 
Australasian Journal of Philosophy ,50, 249–58.
 9. Block, N. (1978). Troubles with functionalism. In Minnesota studies 
in the philosophy of science , Vol. 9 (ed. C. Wade Savage), pp. 261–325. 
University of Minnesota Press, Minneapolis, MN.
10. Jackson, F.C. (2005). The case for a priori physicalism. In Philosophy—
science—scientiﬁ  c philosophy: main lectures and colloquia of GAP.5
(eds. C. Nimtz and A. Beckermann), pp. 251–65. Fifth International Congress of the Society for Analytical Philosophy, Bielefeld, 22–26 September 2003. Mentis, Paderborn.
11. Wittgenstein, L. (1981). Zettel , (eds. G.E.M. Anscombe and 
G.H. von Wright, trans. G.E.M. Anscombe), Sections 608–9. Basil Blackwell, Oxford.
12. Davidson, D. (1973). Radical interpretation. Dialectica ,27,
313–28. Reprinted in Davidson, D. (1984). Inquiries into truth and

313–28. Reprinted in Davidson, D. (1984). Inquiries into truth and 
interpretation , pp. 125–39. Oxford University Press, Oxford.
13. Dennett, D.C. (1987). True believers: the intentional strategy and why it 
works. In The intentional stance , pp. 13–35. MIT Press, Cambridge, MA.
14. Chalmers, D.J. (1996). The conscious mind: in search of a fundamental 
theory.  Oxford University Press, Oxford.
15. Levine, J. (1983). Materialism and qualia: the explanatory gap. Paciﬁ  c 
Philosophical Quarterly ,64, 354–61.
16. Nagel, T. (1974). What is it like to be a bat? Philosophical Review ,83,
435–50. Reprinted in Nagel, T. (1979). Mortal questions , pp. 165–80. 
Cambridge University Press, Cambridge, UK.
17. Chalmers, D.J. (2007). Naturalistic dualism. In The Blackwell 
companion to consciousness (eds. M. Velmans and S. Schneider), pp. 
359–68. Blackwell Publishing, Oxford.

18. McDowell, J. (1985). Functionalism and anomalous monism. 
In Actions and events: perspectives on the philosophy of Donald Davidson
(eds. E. LePore and B.P . McLaughlin), pp. 387–98. Basil Blackwell, Oxford.
19. Dennett, D.C. (1969). 
Content and consciousness , pp. 91–4. Routledge 
and Kegan Paul, London.
20. Davies, M. (2000). Interaction without reduction: the relationship 
between personal and sub-personal levels of description. Mind and 
Society ,1, 87–105.

2.2
Research into mental illness uses a much wider variety of statistical 
methods than those familiar to a typical medical statistician. In many ways there is more similarity to the statistical toolbox of the sociologist or educationalist. It would be a pointless exercise to try to describe this variety here but, instead, we shall cover a few areas that are especially characteristic of psychiatry. The ﬁ  rst 
and perhaps the most obvious is the problem of measurement. Measurement reliability and its estimation are discussed in the next section. Misclassiﬁ  cation errors are a concern of the third section, a 
major part of which is concerned with the estimation of prevalence through the use of fallible screening questionnaires. This is followed by a discussion of both measurement error and misclassiﬁ  cation 
error in the context of modelling patterns of risk.
Another major concern is the presence of missing data. Although

Another major concern is the presence of missing data. Although 
this is common to all areas of medical research, it is of particular 
interest to the psychiatric epidemiologist because there is a long tradition (since the early 1970s) of introducing missing data by design. Here we are thinking of two-phase or double sampling (often confusingly called two-stage sampling by psychiatrists and other clinical research workers). In this design a ﬁ  rst-phase sample 
are all given a screen questionnaire. They are then stratiﬁ  ed on the 
basis of the results of the screen (usually, but not necessarily, using two strata—likely cases and likely non-cases) and subsampled for a second-phase diagnostic interview. This is the major topic of the third section.
If we are interested in modelling patterns of risk, however, we are

If we are interested in modelling patterns of risk, however, we are 
not usually merely interested in describing patterns of association. Typically we want to know if genetic or environmental exposures have a causal effect on the development of illness. Similarly, a clini-cian is concerned with answers to the question ‘What is the causal effect of treatment on outcome?’ How do we deﬁ  ne a causal effect? 
How do we measure or estimate it? How do we design studies in order that we can get a valid estimate of a causal effect of treatment? Here we are concerned with the design and analysis of randomized controlled trials (RCTs). This is the focus of the fourth section of the present chapter.
Finally, at the end of this chapter pointers are given to where the 
interested reader might ﬁ  nd other relevant and useful material on 
psychiatric statistics.Reliability of instruments
In this section we consider two questions:
◆ What is meant by ‘reliability’?
◆ How do we estimate reliabilities?

Models and deﬁ  nitions
Most clinicians have an intuitive idea of what the concept of reliabil-
ity means, and that being able to demonstrate that one’s measuring instruments have high reliability is a good thing. Reliability concerns the consistency of repeated measurements, where the repetitions might be repeated interviews by the same interviewer, alternative ratings of the same interview (as a video recording) by different raters, alternative forms or repeated administration of a question-naire, or even different subscales of a single questionnaire, and so on. One learns from elementary texts that reliability is estimated by a correlation coefﬁ  cient (in the case of a quantitative rating) or a 
kappa ( κ) or weighted κ statistic (in the case of a qualitative judge-

ment such as a diagnosis). Rarely are clinicians aware of either the formal deﬁ  nition of reliability or of its estimation through the use of 
various forms of intraclass correlation coefﬁ  cient rho ( ρ).
First consider a quantitative measurement X. We start with the 
assumption that it is fallible and that it is the sum of two compo-nents: the ‘truth’ T and ‘error’ E. If T and E are statistically inde-
pendent (uncorrelated), then it can be shown that
Var( X) = Var( T) + Var( E) (2.2.1)
where Var( X) is the variance of X (i.e. the square of its standard 
deviation), and so on. The reliability ρ
x of X is deﬁ  ned as the pro-
portion of the total variability of X (i.e. Var( X)) that is explained by 
the variability of the true scores (i.e. Var( T)):
ρx  =Var( T)  =Var( T)
       Var( X)       Var( T)+ Var( E) (2.2.2)
This ratio will approach zero as the variability of the measurement

This ratio will approach zero as the variability of the measurement 
errors increases compared with that of the truth. Alternatively, it will approach one as the variability of the errors decreases. The standard deviation of the measurement errors (i.e. the square root of Var( E)) is usually known as the instrument’s standard error of 
measurement. Note that reliability is not a ﬁ  xed characteristic of Statistics and the design of 
experiments and surveys

138
an instrument, even when its standard error of measurement (i.e. 
its precision) is ﬁ  xed. When the instrument is used on a population 
that is relatively homogeneous (low values of Var( T)), it will have a 
relatively low reliability. However, as Var( T) increases then so does 
the instrument’s reliability. In many ways the standard error of measurement is a much more useful summary of an instrument’s performance, but one should always bear in mind that it too might vary from one population to another—a possibility that must be carefully checked by both the developers and users of the instrument.
Now let us complicate matters slightly. Suppose that a rating 
depends not only on the subject’s so-called true score T and random 
measurement error E, but also on the identity R, say, of the inter-
viewer or rater R. That is, each rater has his or her own charac-

teristic bias (constant from assessment to another) and the biases can be thought of as varying randomly from one rater to another. Again, assuming statistical independence, we can show that, if X = 
T + R + E, then
Var( X) = Var( T) + Var( R) + Var( E) (2.2.3)
But what is the instrument’s reliability? It depends. If subjects 
in a survey or experiment, for example, are each going to be assessed by a rater randomly selected from a large pool of possible raters, then
ρ
xa =Var( T)  =Var( T)
            Var( X)       Var( T) + Var( R) + Var( E) (2.2.4)
However, if only a single rater is to be used for all subjects in the 
proposed study, there will be no variation due to the rater and the reliability now becomes
ρ
xb  =Var( T)
              Var( T) + Var( E) (2.2.5)
Of course, ρxb > ρxa. Again, the value of the instrument’s reliability

ρ
xb  =Var( T)
Of course, ρxb > ρxa. Again, the value of the instrument’s reliability 
depends on the context of its use. This is the essence of generaliza-bility theory.
(1) The three versions of ρ given above are all intraclass 
correlation coefﬁ  cients and are also examples of what generaliza-
bility theorists refer to as generalizability coefﬁ  cients.
Designs
Now consider two simple designs for reliability (generalizability) 
studies. The ﬁ  rst involves each subject of the study being independ-

Designs
ently assessed by two (or more) raters but that the raters for any given subject have been randomly selected from a very large pool of potential raters. The second design again involves each subject of the study being independently assessed by two (or more) raters, but in this case the raters are the same for all subjects. Equations (2.2.1) and (2.2.2) are relevant to the analysis of data arising from the ﬁ  rst design, whilst eqns (2.2.3–2.2.5) are relevant 
to the analysis of data from the second design.
Estimation of r and k from ANOVA  tables
When we come to analyse the data it is usually appropriate to carry 
out an analysis of variance ( ANOV A ). For the ﬁ  rst design we carry 
out a one-way anova  (X by subject) and for the second we perform 
a two-way anova  (X by rater and subject). In the latter case we

a two-way anova  (X by rater and subject). In the latter case we 
assume that there is no subject by rater interaction and accordingly constrain the corresponding sum of squares to be zero. We assume that readers are reasonably familiar with an analysis of variance table. Each subject has been assessed by, say, k raters. The one-way 
anova  yields a mean square for between-subjects variation ( BMS )
and a mean square for within-subjects variation ( WMS ). WMS is 
an estimate of Var( E) in eqn. (2.2.1). Therefore, the square root of 
WMS provides an estimate of the instrument’s standard error of measurement. The corresponding estimate of ρ
x is given by
rx  =BMS − WMS
             BMS + ( k−1)WMS (2.2.6)
where rx is used to represent the estimate of ρx rather than the true, 
but unknown, value. In the case of k = 2, rx becomes
             BMS + WMS (2.2.7)

In the slightly more complex two-way anova , the anova  table pro-
vides values of mean squares for subjects or patients ( PMS ), raters 
(RMS ), and error ( EMS ). We shall not concentrate on the details 
of estimation of the components of eqn. (2.2.3) (see Fleiss(2) or 
Streiner and Norman(3)) but simply note that ρxa is estimated by
rxa  =n(PMS − EMS)
n× PMS + k× RMS + ( nk− n− k)EMS (2.2.8)
where n is the number of subjects (patients) in the study.
In reporting the results of a reliability study, it is important that 
investigators give some idea of the precision of their estimates of reliability, for example by giving an appropriate standard error or, even better, an appropriate conﬁ  dence interval. The subject is 
beyond the scope of this chapter, however, and the interested reader is referred to Fleiss

(2) or Dunn(4) for further illumination.
Finally, what about qualitative measures? We shall not discuss the 
estimation and interpretation of κ in any detail here but simply 
point out that for a binary (yes/no) measure one can also carry out a two-way analysis of variance (but ignore any signiﬁ  cance tests 
since they are not valid for binary data) and estimate r
xa as above. 
In large samples rxa is equivalent to κ.(3) A corollary of this is that κ
is another form of reliability coefﬁ  cient and, like any of the reliabil-
ity coefﬁ  cients described above, will vary from one population to 
another (i.e. it is dependent on the prevalence of the symptom or characteristic being assessed).
Prevalence estimation
Following Dunn and Everitt,(5) we ask the following questions of 
a survey report.
◆ Do the authors clearly deﬁ  ne the sampled population?

◆ Do the authors discuss similarities and possible differences 
between their sampled population and the stated target population?
◆ Do the authors report what sampling mechanism has been used?
◆ Is the sampling mechanism random? If not, why not?
◆ Exactly what sort of random sampling mechanism has been 
used?
◆ Do the methods of data analysis make allowances for the 
sampling mechanism used?SECTION 2  the scientific basis of psychiatric aetiology

139
Of course, it is vital that what counts as a case should be explained 
in absolute detail, including the method of eliciting symptoms (e.g. structured interview schedule), screening items, additional impair-ment criteria, and so on, as well as operational criteria or algorithms used in making a diagnosis. In the following we concentrate on the statistical issues. First, we consider survey design (and the asso-
ciated sampling mechanisms), and then we move on to discuss the 
implications of design for the subsequent analysis of the results.
Survey design

Here we are concerned with the estimation of a simple proportion (or percentage). We calculate this proportion using data from the sample and use it to infer the corresponding proportion in the underlying population. One vital component of this process is to ensure that the sampled population from which we have drawn our subjects is as close as possible to that of the target population about which we want to draw conclusions. We also require the sample to be drawn from the sample population in an objective and unbiased way. The best way of achieving this is through some sort of random sampling mechanism. Random sampling implies that whether or not a subject ﬁ  nishes up in the sample is determined by chance. 
Shufﬂ  ing and dealing a hand of playing cards is an example of a

Shufﬂ  ing and dealing a hand of playing cards is an example of a 
random selection process called simple random sampling. Here every possible hand of, say, ﬁ  ve cards has the same probability of 
occurring as any other. If we can list all possible samples of a ﬁ  xed 
size, then simple random sampling implies that they all have the 
same probability of ﬁ  nishing up in our survey. It also implies that 
each possible subject has the same probability of being selected. But note that the latter condition is not sufﬁ  cient to deﬁ  ne a simple 
random sample. In a systematic random sample, for example, we have a list of possible people to select (the sampling frame) and we simply select one of the ﬁ  rst 10 (say) subjects at random and

random sample. In a systematic random sample, for example, we have a list of possible people to select (the sampling frame) and we simply select one of the ﬁ  rst 10 (say) subjects at random and 
then systematically select every tenth subject from then on. All subjects have the same probability of selection, but there are many samples which are impossible to draw using this mechanism. For example, we can select either subject 2 or subject 3 with the same probability (1/10), but it is impossible to draw a sample which contains both.
What other forms of random sampling mechanisms might be 
used? Perhaps the most common is a stratiﬁ  ed random sample. 
Here we divide our sampled population into mutually exclusive groups or strata (e.g. men and women, or ﬁ  ve separate age groups).

Here we divide our sampled population into mutually exclusive groups or strata (e.g. men and women, or ﬁ  ve separate age groups). 
Having chosen the strata, we proceed, for example, to take a sepa-rate simple random sample from each. The proportion of subjects sampled from each of the strata (i.e. the sampling fraction) might be constant across all strata (ensuring that the overall sample has the same composition as the original population), or we might decide that one or more strata (e.g. the elderly) might have a higher representation. Another commonly used sampling mechanism is multistage cluster sampling. For example, in a national prevalence survey we might chose ﬁ  rst to sample health regions or districts, 
then to sample post codes within the districts, and ﬁ  nally to select 
patients randomly from each selected post code. (See Kessler
(6) and 
Jenkins et al .(7) for discussions of complex multistage surveys of

(6) and 
Jenkins et al .(7) for discussions of complex multistage surveys of 
psychiatric morbidity.)
One particular design that has been used quite often in surveys 
designed to estimate the prevalence of psychiatric disorders is called two-phase or double sampling. Psychiatrists frequently refer to this as two-stage sampling. This is unfortunate, since it confuses the two-phase design with simple forms of cluster sampling in which the ﬁ  rst-stage involves drawing a random sample of clusters 
and the second-stage a random sample of subjects from within each of the clusters. In two-phase sampling, however, we ﬁ  rst draw 
a preliminary sample (which may be simple, stratiﬁ  ed, and/or clus-
tered) and then administer a ﬁ  rst-phase screening questionnaire 
such as the General Health Questionnaire (see Chapter 1.8.1). On the basis of the screen results we then stratify the ﬁ  rst-phase

such as the General Health Questionnaire (see Chapter 1.8.1). On the basis of the screen results we then stratify the ﬁ  rst-phase 
sample. Note that we are not restricted to two strata (likely cases 
versus the rest), although this is perhaps the most common form of 
the design. We then draw a second-phase sample from each of the ﬁ rst-phase strata and proceed to give these subjects a deﬁ  nitive 
psychiatric assessment. The point of this design is that we do not waste expensive resources interviewing large numbers of subjects who not appear (on the basis of the ﬁ  rst-phase screen) to have 
any problems. Accordingly, the sampling fractions usually differ across the ﬁ  rst-phase strata. However, it is vital that each of the 
ﬁ rst-phase strata have a reasonable representation in the second-
phase, and it is particularly important that all of the ﬁ  rst-phase

phase, and it is particularly important that all of the ﬁ  rst-phase 
strata provide some second-phase subjects. The reader is referred to Pickles and Dunn
(8) for further discussion of design issues in 
two-phase sampling (including discussion of whether it is worth the bother).
Analysis of the results
Here we are particularly concerned with the last of the questions posed at the beginning of the section. In fact, it is a question that should be asked not only of prevalence surveys but of all investiga-tions whether they are epidemiological surveys, intervention studies, 
or laboratory experiments. How was the design incorporated in the analysis? Frequently the required information is missing. Either the authors are ignorant of the implications of the design, or the journal editor has insisted that technical details are stripped from the report, or both.
Consider a hypothetical sample of 100 participants who have

Consider a hypothetical sample of 100 participants who have 
contributed to an estimate of prevalence of, say, depression using a deﬁ nitive psychiatric interview.
Seventy of the participants have been given a diagnosis of depres-
sion. What is a valid estimate of prevalence? What is the standard error of the estimate? Assuming that the data have arisen through 
simple random sampling, the prevalence p is estimated by 0.70 
and its variance is given by
Var( p)  =1
np(1− p) (2.2.9)
where n is the sample size. The standard error is then given by the 
square root of this expression.
Suppose that we are now told that the results were obtained from 
a two-phase survey. The size of the ﬁ  rst-phase sample was 300. Of 
these, 100 were screen positive and 200 were screen negative. The second-phase sample consisted of 70 screen positives, of whom 65 were found to be depressed on interview, together with 30 screen negatives, of whom 5 were found to be depressed on interview. The

estimate of prevalence is given by
p=P(screen +ve)  ×  P(interview +ve|screen +ve) + P(screen − ve) 
×  P(interview +ve|screen −ve)
   = (100/300) ×  (65/70) + (200/300)  ×  (5/30)
   = 0.42 (2.2.10)2.2 statistics and the design of experiments and surveys

SECTION 2  the scientific basis of psychiatric aetiology 140
where P(A) should be read as ‘probability of A’ and P(A|B) should 
be read as ‘probability of A given B’ or ‘probability of A conditional 
onB having occurred’ . The vertical ‘|’ should not be confused with 
division, represented by ‘/’ .
The prevalence estimate from the two-phase survey is consider-
ably lower than if simple random sampling had been assumed. How has this arisen? Obviously the second-phase sample has been enriched for people who are likely to be depressed. The sampling fraction for the screen positives is 70/100, that is each second-phase participant can be thought of as representing 100/70 of screen positives from the original sample. Similarly, the sampling fraction for the screen negatives is 30/200, and each second-phase partici-pant represents 200/30 screen-negative participants from the ﬁ rst-phase sample. The reciprocal of the sampling fraction is called

the sampling weight. The total weighted second-phase sample size is 70 × (100/70) + 30 × (200/30) = 300, the ﬁ  rst-phase sample. 
Similarly, the total weighted number of cases of depression is 65 × (100/70) + 5 × (200/30) ≈ 126. The latter is the estimate of the 
number of cases in the ﬁ  rst-phase sample. Hence the estimate of 
prevalence is 126/300 = 0.42, as before. T o recapitulate in a slightly 
more technical way, if the ith individual in the second-phase sam-
ple is assigned a sampling weight w
i, and if the interview outcome 
yi has a value of 1 if the ith subject is a case and is 0 otherwise, then 
the weighted prevalence estimate is given by
p = Σwiyi/Σwi (2.2.11)
where Σ means ‘sum over all observations in the second-phase 
sample’ and xi is simply an indicator that the observation is, indeed, 
a second-phase observation ( xi = 1 for everyone). This estimator is 
an example of the well-known Horwitz–Thompson estimator from the sampling survey literature

(9) but it is not particular familiar to 
psychiatrists or medical statisticians. We shall discuss the use of weighting adjustments again below.
Returning to our original two-phase calculations, let A = P(screen 
+ve) and B = 1– A = P(screen –ve). Also, let p = P(interview 
+ve|screen +ve) and q = P(interview +ve|screen –ve), so that eqn. 
(2.2.10) becomes
p = Ap + Bq (2.2.12)
The variance of the estimate of prevalence from the two-phase 
design is given by
(10)
Var( p) =A2p(1−p)  +B2q(1−q)  +(p−q)2AB
n1 n2 n3 (2.2.13)
where n1 is the number of ﬁ  rst-phase screen positives and n2 is the 
number of ﬁ  rst-phase screen negatives (and n = n1+n2 is the total 
(ﬁ rst phase) sample size).
Validation of screening questionnaires
It is frequently the case that data from a two-phase survey which

It is frequently the case that data from a two-phase survey which 
has been designed to estimate prevalence are also used to examine the characteristics of the screen questionnaire (in particular, sensi-tivity and speciﬁ  city). Readers who are unfamiliar with these 
concepts are referred to Chapter 2.7 or to Goldberg and Williams.
(11)
Sensitivity is the proportion of true cases who are screen positive. Speciﬁ  city is the proportion of true non-cases who are screen 
negative. The trouble is caused because we used the screen ﬁ  rst and 
then differentially subsampled to carry out the deﬁ  nitive diagnostic interview. Readers familiar with the use of Bayes’ theorem will real-
ize how to solve the problem, but here we use another version of the Horwitz–Thompson estimator:
Sensitivity = Σw
iyizi/wiyi (2.2.14)
and
1−speciﬁ  city = Σwi(1−yi)zi/Σwi(1−yi) (2.2.15)

and
where, as before, yi indicates whether the ith subject was a true case 
of depression (1 = yes, 0 = no). This ensures that the calculations in eqn (2.2.14) are only being carried out on the true cases and, similarly, that the calculations in (2.2.15) are only being carried out on the non-cases. Again, w
i is the second-phase sampling weight. 
The new variable zi indicates whether the screen result was positive

The new variable zi indicates whether the screen result was positive 
(1 = yes, 0 = no). An alternative, and perhaps easier, approach is to split the second-phase sample into two: cases and non-cases. Estimation of sensitivity and specificity in these two subfiles (assuming that they are being stored on a computer) is then com-putationally exactly the same as the weighted estimation of preva-lence discussed in the previous section. In the ﬁ  rst ﬁ  le, sensitivity is 
simply the weighted sum of the screen positives divided by the weighted sum of the cases. Similarly, in the second ﬁ  le, speciﬁ  city is 
the weighted sum of the screen negatives divided by the weighted sum of the non-cases.
Many readers will be familiar with the idea of choosing a range 
of cut-points for the screen questionnaire and then estimating sensitivity and speciﬁ  city at each of the choices. A plot of sensitivity

of cut-points for the screen questionnaire and then estimating sensitivity and speciﬁ  city at each of the choices. A plot of sensitivity 
against 1—speciﬁ  city is called a receiver operating characteristic 
(ROC ) curve. If the screen is of no use, then the plot will be a 
straight line through the origin with unit slope. A good screen will produce a convex curve (the greater the area between the observed curve and that indicated by a straight line with unit slope, the better the screen is at discriminating between cases and non-cases). It is sometimes said that one cannot investigate ROC curves using two-phase data. This view is, in fact, mistaken. One can think of the two-phase sampling design as a mechanism by which one can deliberately introduce the analogues of veriﬁ  cation bias.
(12) Note 
that there is no necessity to restrict the ﬁ  rst-phase stratiﬁ  cation 
to just two strata (potential cases versus non-cases) to deﬁ  ne the

(12) Note 
to just two strata (potential cases versus non-cases) to deﬁ  ne the 
sampling fractions for the second-phase of the survey. We start by calculating observed sampling fractions for each discrete outcome of the screening questionnaire. These deﬁ  ne the corresponding 
sampling weights. We then consider all the possibilities for deﬁ  ning 
z
i in eqns (2.2.14) and (2.2.15)—there is no need for the zi to 
correspond to the way that the second-phase sampling fractions were determined. We then repeatedly use eqns (2.2.14) and (2.2.15), keeping the weights constant as we change the deﬁ  nition of the z
i.
One important point to bear in mind is that if the characteristics of the screen are not fairly well known beforehand and if one of the major aims of the survey is to carry out an ROC analysis, then this is not a particularly efﬁ  cient design to use. It would be better to go

back to the simple random sample—all subjects assessed by both screen and interview.
If one needs, say, conﬁ  dence intervals for estimates of sensitivity 
and speciﬁ  city, it is relatively straightforward to do this via a 
weighted logistic regression (see next section). The ﬁ  le can be split 
into cases and non-cases and then, using appropriate software (see below), one ﬁ  ts a logistic model containing a predictor variable

141
which has the value of 1 for all subjects (i.e. just ﬁ  tting a constant). 
One then obtains the conﬁ  dence interval for the intercept term in 
the output. Finally, the inverse of the logistic transformation of the lower and upper conﬁ  dence limits will yield the corresponding 
limits for the sensitivity (speciﬁ  city) itself. Note that the interval 
will be asymmetric and will be within the permitted bounds of zero and unity.
Modelling patterns of risk
Henderson (see Chapter 2.7) has introduced the idea of an odds ratio to measure the association between a suspected risk factor and disease. In a linear logistic model the response variable is the natural logarithm of the odds (of disease). Therefore the difference between two groups on this logistic scale (i.e. log( a/b)–log( c/d)
using Henderson’s notation) is equivalent to the logarithm of the odds ratio (i.e. log( ad/bc)). This provides us with an easy way to 
calculate conﬁ  dence intervals for odds ratio: log(odds ratio) or

calculate conﬁ  dence intervals for odds ratio: log(odds ratio) or 
log(ad/bc) is normally distributed with variance 1/ a + 1/ b + 1/ c + 
1/d (the corresponding standard error is the square root of this 
variance). The 95 per cent conﬁ  dence interval for the log(odds 
ratio), for example, is then the point estimate plus or minus 1.96 standard errors. Taking exponents (antilogarithms) of these limits provides the corresponding limits for the odds ratio itself. The exponent of the parameter estimate in the output of the logistic regression run provides the point estimate for the corresponding odds ratio.
The great advantage of logistic regression is that it enables us to

The great advantage of logistic regression is that it enables us to 
model the potential effects of several risk factors simultaneously. It allows us to adjust for the effects of suspected confounder(s) in assessing the effects of a risk factor of interest. Logistic regression can also be generalized to cope with the use of sampling weights, either to cope with data missing by design (as in a two-phase sur-vey) or to allow for non-response and/or attrition.
(13) However, 
one must be very wary of using weights in software packages that do not explicitly deal with sampling weights. Many packages have weighting functions but these are interpreted as frequency weights—the number of times the observation has been made instead of the number of times it might have been made (as in the case of a sampling weight). The use of frequency weights, as opposed to sampling weights, produces standard errors, and conﬁ  -

dence intervals that are far too small. This is not a subtle effect; it can make an enormous difference to a P value, giving the impres-
sion of a highly signiﬁ  cant effect when, in reality, there is little or 
nothing there.
(14) We illustrate this point by reference to a two-
phase survey of psychiatric morbidity in Cantabria in Northern Spain.
(15, 16)  The weighted prevalence estimate from these data is 
31 per cent. The appropriate 95 per cent conﬁ  dence interval ( CI), 
obtained using sampling weights is (26 per cent, 40 per cent). The naive use of frequency weights produces a 95 per cent CI of (28 per cent, 35 per cent), which is much too narrow. The odds 
ratio indicating how much higher the prevalence of disorder is in

ratio indicating how much higher the prevalence of disorder is in 
women compared with men is 2.02 with a 95 per cent CI of (0.86, 4.74). The naive use of frequency weights gives the same point estimate (2.02), but here the 95 per cent CI is (1.45, 2.77); again, this is much too narrow. In the analysis of a similar study from Verona in Northern Italy, Dunn et al .
(14) found a corresponding 
odds ratio of 2.85 with a 95 per cent CI of (1.31, 6.19). The P value 
for this odds ratio is about 0.008. The incorrect use of frequency weights gives us a 95 per cent CI of (2.31, 3.53) and a correspond-
ingP value of less than 0.00001—at least an 800-fold difference!
Evaluating treatment effects
Readers will be familiar with the challenges posed by confounding

Readers will be familiar with the challenges posed by confounding 
in trying to validly infer an effect of an exposure on the develop-ment of illness from data arising from an observational study (or epidemiological survey). We can model patterns of risk (as in the above section) but we can never be sure that we have allowed for all possible sources of confounding (i.e. the effects of unmeasured variables that are associated with the exposure of interest and also inﬂ uence outcome) in assessing the effect of a particular risk factor. 
The same challenges apply to the use of observational data to the evaluation of the effect of a treatment or other intervention. Although it may be possible to obtain valid treatment effect estimates from observational data,
(17, 18) the ideal is to use a randomized

(17, 18) the ideal is to use a randomized 
experiment. Allocation of treatments by randomization ensures that there are no systematic selection effects (i.e. no biases arising from hidden confounding) and enables the investigator to obtain valid measurements of uncertainty (i.e. valid p-values, standard errors, and conﬁ  dence intervals).
How do we define a causal effect of treatment? Following 
Rubin
(19) we deﬁ  ne it as the comparison between potential out-
comes or counterfactuals. For a patient who has received treatment we deﬁ  ne the treatment effect as a comparison between the outcome 
that we have observed after the receipt of treatment ( Y
t, say) with 
that we would have observed if, contrary to fact, the same patient had not received the treatment ( Y
c, say the subscript c indicating a 
control condition). For a patient who has not received treatment we compared the observed outcome ( Y
c, in this case) with the

c, in this case) with the 
unobserved counterfactual ( Yt). Typically, we might be interested in 
the difference ( Yt–Yc) but ratios might also be of interest. We deﬁ  ne 
the Average Causal Effect (ACE) of treatment as the average ( Ave—
over the whole of the population of interest) of the individual treatment effects, that is
ACE = Ave( Y
t−Yc) (2.2.16)
But, of course we can only ever observe either Yt or Yc, not both. 
We can never observe an individual treatment effect and therefore cannot obtain a direct estimate of the average. But we note that
ACE = Ave( Y
t)− Ave( Yc) (2.2.17)
and if we could obtain valid estimates of Ave( Yt) and Ave( Yc) then

ACE = Ave( Y
and if we could obtain valid estimates of Ave( Yt) and Ave( Yc) then 
the problem would be solved. The only sure way of knowing that we have a valid estimate of these two averages (i.e. no selection biases) is to make sure that the allocation of treatment is completely random. Hence the Randomized Controlled Trial (RCT). Of course, we have to ensure that we have eliminated or reduced all other potential sources of bias (e.g. by masking treatment allocation from the people assessing outcomes) and one must not automatically assume that randomization has led to a perfect trial. In the critical appraisal of a clinical trial report, one might ask:
◆ What is the target population for the evaluation of the treatment, 
and were the trial participants representative of this population?
◆ Were the treatment and control conditions clearly defined

◆ Were the treatment and control conditions clearly defined 
and operationalized? In particular, was the control condition convincing?2.2 statistics and the design of experiments and surveys

SECTION 2  the scientific basis of psychiatric aetiology 142
◆ Were outcomes clearly deﬁ  ned and reliably measured?
◆ Was the trial adequately powered (i.e. was the number of 
randomized participants adequate for the job at hand)?
◆ Was randomization used to allocate treatment and how was the 
randomization actually implemented?
◆ Was it possible to blind mask treatment allocation from all those 
concerned with the assessment of outcomes? What evidence has been provided to indicate that masking has been effective?
◆ What methods were used to estimate the treatment effects and 
their precision? Were they fully compatible with the trial design (the randomization procedure)? Did the analysis take account of everyone randomized? In particular, did the analysis deal adequately with missing outcome data?
◆ If the trial used a non-standard design (randomization of groups

◆ If the trial used a non-standard design (randomization of groups 
of participants rather than of individuals; use of group-based therapies; and so on) were the power calculations and methods of statistical analysis appropriate for this design?
Estimation of treatment efﬁ  cacy in the presence of 
non-compliance
What if the trial participants, despite giving their consent to be 
randomized, do not receive the treatment to which they were allo-cated? In a drug trial the participants may not take the tablets, or take less than the prescribed amount. They may even receive the active medication despite being allocated to the placebo (control) condition. In a psychotherapy trial they may not turn up to all or even any of the planned sessions of therapy. The standard method of analysis (and justiﬁ  ably so) is based on the so-called Intention-

to-Treat (ITT) principle: we analyse as randomized. We evaluate the effect of the offer of treatment as opposed to its receipt. But what do we do if we wish to evaluate (estimate) the effect of the treatment actually received? Two commonly used methods of analysis are called per Protocol and As Treated estimators. In the ﬁ rst method the effect of randomization is evaluated after ﬁ  rst 
discarding the people who did not adhere to (or comply with) their 
allocated treatment. In the second, we compare the outcomes of all those who receive the treatment with all of those who received the control condition, regardless of their random allocation. Both methods are potentially ﬂ  awed—they take no account of possible

selection effects (confounding). A much better approach is to esti-mate the effect of randomization in that subgroup of participants who would always have complied with their treatment allocation whatever the outcome of the randomization. We call this subgroup the Compliers (the rest being non-compliers), and we aim to estimate the Complier-Average Causal Effect of Treatment (CACE).
(20,21)  In effect we are obtaining an ITT effect for the 
Compliers. Randomization ensures that, on average, the propor-tion ( P) of Compliers is the same in each arm of the trial. The 
overall ITT effect is a weighted average of the ITT effect in the Compliers and the ITT effect in the non-compliers (the weights being P and 1- P, respectively). If we are prepared to assume that 
there is no direct effect of randomization on outcome (in particu-lar, there is no effect of randomization on outcome in the non-compliers) then
ITT
All = P.ITTCompliers+(1−P).ITTnon-compliers

ITT
          = P.ITTCompliers (2.2.18)It follows that
CACE = ITTcompliers  =ITTAll
P (2.2.19)
It is easy to show that in a trial in which no-one allocated to the 
control condition gets access to the (potentially) active treatment the proportion of Compliers ( P) is estimated by the proportion 
of Compliers in the treatment group (this follows directly from randomization). In the situation in which participants allocated to the control condition can get access to treatment P is estimated by 
the difference between the two randomized groups with respect to the proportion of participants receiving treatment. Considering everyone randomized, eqn (2.2.19) is the ratio of the ITT effect on outcome to the ITT effect on receipt of treatment. Note that ITT
All

All
and CACE (ITTCompliers) share the same null hypothesis (when 
one is zero, so is the other) and a signiﬁ  cance test for one of them is 
equivalent to the corresponding signiﬁ  cance test for the other. The 
estimation of the CACE is simply a way of adjusting the overall ITT estimate to allow to attenuation in the presence of non-compliance. It will not reveal a signiﬁ  cant treatment effect when we already have 
a non-signiﬁ  cant ITT estimate.
We do not advocate the replacement of ITT estimates by 
CACE estimation, but we do recommend that investigators supple-ment their primary ITT analyses with more detailed explanatory methods, particularly when there are situations in which non-compliance is strongly associated with subsequent loss to follow-up (i.e. missing outcome data). Valid ITT (and any other) estimates are particularly difﬁ  cult to obtain in the presence of missing data. 
This is an active area of theoretical development in medical

This is an active area of theoretical development in medical 
statistics, but the more easily understood methods are now begin-ning to make the transition to the more easily accessible clinical journals. For example, a relatively non-technical discussion of the potential application to mental health trials is provided by Dunn et al.
(22,23)
We refer readers to Everitt and Wessely(24) and Dunn(25) for a 
much more detailed discussion of the methodological pitfalls for RCTs in psychiatry. One important point needs stressing again, however. It is vital that RCTs involve the randomization of sufﬁ  -
cient numbers of subjects to be conﬁ  dent that the trial has sufﬁ  -
cient power to detect the minimum  treatment effect that still has 
clinical  (as opposed to statistical) signiﬁ  cance. This minimum effect 
should be deﬁ  ned in terms of its importance and not by naively 
observing the results of previous trials or pilot investigations.

The recently published Encyclopedia of Biostatistics(26) comprises of

The recently published Encyclopedia of Biostatistics(26) comprises of 
six large volumes of chapters such as this one, covering every area of conceivable interest to the statistically interested clinical research worker. Therefore it is inevitable that this chapter should be very restricted. Inevitably, the choice of topics might be thought to be rather idiosyncratic. Areas which might have been covered, but have been ignored, include survival modelling (particularly recent developments in so-called frailty modelling), longitudinal data analysis (with special reference to modelling patterns of attrition), genetics, and a whole range of classical multivariate methods such as principal components and factor analysis, discriminant analysis (although logistic modelling is one of the better methods of discri-minant analysis), multidimensional scaling, and cluster analysis.

143
Henderson (see Chapter 2.7) has also mentioned exciting possibili-
ties for the development of latent trait (item response theory) and latent class models. Several years ago I was often asked to teach trainee psychiatrists all they needed to know about statistics in two 2-h sessions. The ﬁ  rst was to cover univariate methods, and the 
second, multivariate analysis. It cannot be done!

So, where should the reader go from here? Which are the most use-ful textbooks? In terms of general medical statistics, the obvious choice is Armitage, Berry, and Matthews. Everitt and Dunn and Everitt provide general introductions to multivariate methodology. Measurement error problems, including structural equation model-ling, are covered by Dunn. The role of statistics in genetics is well covered by Sham. Although there are many texts on the use of statistics in psychology and education (e.g. Plewis which includes an introduction to multilevel modelling), the only specialist reference for psychiatrists appears to be that by Dunn.
Armitage, P ., Berry, G., and Matthews, J.N.S. (2002). Statistical methods in 
medical research  (4th edn). Blackwell Science, Oxford.
Everitt, B.S. and Dunn, G. (2001). Applied multivariate data analysis
(2nd edn). Arnold, London.

Everitt, B.S. (1996). Making sense of statistics in psychology . Oxford 
Sham, P . (1998). Statistics in human genetics . Arnold, London.
Dunn, G. (1999). Statistics in psychiatry . Arnold, London.
Plewis, I. (1997). Statistics in education . Arnold, London.
1. Shavelson, R.J. and Webb, N.M. (1991). Generalizability theory: 
a primer . Sage, Thousand Oaks, CA.
2. Fleiss, J.L. (1987). The design and analysis of clinical experiments . Wiley, 
New Y ork.
3. Streiner, D.L. and Norman, G.R. (2003). Health measurement scales: a 
practical guide to their development and use  (3rd edn). Oxford University 
4. Dunn, G. (2004). Statistical evaluation of measurement errors: design and 
analysis of reliability studies  (2nd edn). Arnold, London.

5. Dunn, G. and Everitt, B.S. (1995). Clinical biostatistics: an introduction to 
evidence based medicine , Chap. 4. Arnold, London.
6. Kessler, R.C. (1994). The National Comorbidity Survey of the United 
States. International Review of Psychiatry ,6, 365–76.
7. Jenkins, R., Bebbington, P ., Brugha, T., et al. (1997). The National 
Psychiatric Morbidity Surveys of Great Britain—strategy and methods. Psychological Medicine ,27, 765–74. 8. Pickles, A. and Dunn, G. (1998). Prevalence of disease, estimation from 
screening data. In Encyclopedia of biostatistics , Vol. 5 (eds. P . Armitage 
and T. Colton), pp. 3484–90. Wiley, Chichester.
 9. Lehtonen, R. and Pahkinen, E.J. (1995). Practical methods for design and 
analysis of complex surveys . Wiley, Chichester.
10. Cochran, W.G. (1977). Sampling techniques  (3rd edn). Wiley, New Y ork.

11. Goldberg, D.P . and Williams, P . (1988). A user’s guide to the General 
Health Questionnaire . NFER-Nelson, Windsor.
12. Begg, C.B. and Greenes, R.A. (1983). Assessment of diagnostic tests 
when disease veriﬁ  cation is subject to selection bias. Biometrics ,
39, 207–15.
13. Dunn, G. (1998). Compensating for missing data in psychiatric surveys. 
Epidemiologia e Psichiatria Sociale ,6, 159–62.
14. Dunn, G., Pickles, A., Tansella, M., et al.  (1999). The role of two-phase 
epidemiological surveys in psychiatric research. The British Journal of 
Psychiatry ,174, 95–100.
15. Pickles, A., Dunn, G., and Vázquez-Barquero, J.L. (1995). Screening 
for stratiﬁ  cation in two-phase (‘two-stage’) epidemiological surveys. 
Statistical Methods in Medical Research ,4, 75–91.
16. Vázquez-Barquero, J.L., Garcia, J., Artal Simón, J., et al. (1997). Mental

16. Vázquez-Barquero, J.L., Garcia, J., Artal Simón, J., et al. (1997). Mental 
health in primary care: an epidemiological study of morbidity and use of health resources. The British Journal of Psychiatry ,170, 529–35.
17. Rubin, D.B. (2007). The design versus the analysis of observational 
studies for causal effects: parallels with the design of randomized trials. 
Statistics in Medicine ,26, 20–36.
18.. Luellin, J.K., Shadish, W.R., and Clark, M.H. (2005). Propensity scores: 
an introduction and experimental test. Evaluation Review ,29, 530–58.
19. Rubin, D.B. (1974). Estimating causal effects of treatments in 
randomized and non-randomized studies. Journal of Educational 
Psychology ,66, 688–701.
20. Bloom, H.S. (1984). Accounting for no-shows in experimental 
evaluation designs. Evaluation Review ,8, 225–46.
21. Angrist, J.D., Imbens, G.W., and Rubin, D.B. (1996). Identiﬁ  cation of

21. Angrist, J.D., Imbens, G.W., and Rubin, D.B. (1996). Identiﬁ  cation of 
causal effects using instrumental variables (with discussion). Journal of 
the American Statistical Association ,91, 444–72.
22. Dunn, G. Maracy, M., Dowrick, C., et al. Estimating psychological 
treatment effects from an RCT with both non-compliance and loss to 
follow-up. The British Journal of Psychiatry ,183, 323–31.
23. Dunn, G., Maracy, M., and T omenson, B. (2005). Estimating treatment 
effects from randomized clinical trials with non-compliance and loss to follow-up: the role of instrumental variable methods. Statistical 
Methods in Medical Research ,14, 369–95.
24. Everitt, B.S. and Wessely, S. (2004). Clinical trials in psychiatry . Oxford 
25. Dunn, G. (2006). Psychotherapy for depression. In Textbook of clinical

25. Dunn, G. (2006). Psychotherapy for depression. In Textbook of clinical 
trials  (2nd edn) (eds. D. Machin, S. Day, and S. Green), pp. 377–93. 
John Wiley & Sons, Chichester.
26. Armitage, P . and Colton, T. (eds.) (1998, 2nd edn 2005). Encyclopedia of 
biostatistics . Wiley, Chichester.2.2 statistics and the design of experiments and surveys

2.3
The contribution of 
neurosciences
Contents
 2.3.1 Neuroanatomy
†R. C. A.   Pearson
 2.3.2 Neurodevelopment
 2.3.3 Neuroendocrinology
 2.3.4 Neurotransmitters and signalling
 2.3.5 Neuropathology
 2.3.6 Functional positron emission 
tomography in psychiatry
 2.3.7 Structural magnetic resonance imaging
 2.3.8 Functional magnetic resonance imaging
 2.3.9 Neuronal networks, epilepsy, and other brain dysfunctions
 2.3.10 Psychoneuroimmunology
2.3.1 Neuroanatomy
The symptoms, signs, and syndromes of psychiatry, whether organic 
or biological psychiatric disease or not, in the main reﬂ  ect altera-

tions in functions which reside in the cerebral cortex, including the limbic lobe, and those structures and pathways closely related to 
the cortex. These cortical manifestations of psychiatric disease include alterations in thought, language, perception, mood, mem-ory, motivation, personality, behaviour, and intellect. Therefore, this brief account of brain structures and pathways that are impor-tant in psychiatry will concentrate on the cerebral cortex and related structures and pathways. Readers who require a fuller account of central nervous system anatomy are referred to the many standard texts, which give a more complete coverage of the subject.
Broadly speaking, neuroanatomy can be subdivided into two

Broadly speaking, neuroanatomy can be subdivided into two 
parts—the topographical organization of the brain and spinal cord, and the anatomical connections forming functional pathways in the central nervous system. The former is of vital importance clini-cally, since pathologies rarely respect the boundaries of functional systems, and knowledge of the spatial relationships of different brain structures is increasingly useful as modern imaging methods more accurately visualize detailed brain structure in vivo . However, it 
is the second subdivision of the subject which makes the greater con-tribution to understanding the biological basis of psychiatric disease, and it is this that will be at the centre of the present account.
The structure and organization of the 
cerebral cortex
The lobes of the cerebral cortex
A variable pattern of ﬁ  ssures (sulci) and folds (gyri), many of which 
have speciﬁ  c names, extensively groove the surface of the cerebral

have speciﬁ  c names, extensively groove the surface of the cerebral 
hemisphere. A few are relatively constant and are used to subdividethe cerebral hemisphere into lobes, named for the bones of the skull which they underlie (Fig. 2.3.1.1 ).
The deep lateral sulcus, also called the Sylvian ﬁ  ssure, extends 
from the uncus, anteriorly and medially, to the parietal lobe, poste-riorly and medially. It has a short stem, and anterior, ascending, and posterior rami. The anterior and ascending rami embrace the pars triangularis of the frontal lobe, which houses Broca’s motor speech area. The much longer posterior ramus is used in deﬁ  ning 
the lobes of the hemisphere. The central sulcus is prominent approximately midway along the anteroposterior extent of the 
† Dr. Pearson died while this new edition was being prepared. The editors pay

† Dr. Pearson died while this new edition was being prepared. The editors pay 
tribute to his scientiﬁ  c achievements and to his contributions to this book.

145
lateral surface of the hemisphere and, most commonly, extends 
over the medial margin, where its inferomedial tip is embraced by 
the U-shaped paracentral lobule. On the lateral surface, it passes 
from the medial margin, forwards and laterally, to reach the lateral 
sulcus. The line of the central sulcus closely approximates the line 
of the coronal suture of the adult skull, i.e. the junction between 
the frontal and parietal bones; consequently, the sulcus separates 
the frontal and parietal lobes. The demarcation of the occipital lobe 
is the parieto-occipital sulcus dorsally and medially, and the pre-
occipital sulcus ventrally and laterally, with an imaginary line con-
necting the two and intersecting the posterior tip of the lateral 
sulcus. The temporal lobe lies anterior to this line and inferior (ven-
tral) to the lateral sulcus. The deep lateral sulcus broadens out at its 
fundus, with an area of cortex forming the extensive ﬂ  oor of the

fundus, with an area of cortex forming the extensive ﬂ  oor of the 
sulcus, particularly in its anterior two-thirds. This cortex is the insu-
la, which does not form part of any of the lobes mentioned above. 
The insula is surrounded by the circular sulcus, and is overhung by 
the frontal and parietal opercula superiorly, and the temporal oper-
culum inferiorly (ventrally). The anatomical borders of the lobes of 
the cerebral cortex, and other sulcal and gyral landmarks, are only 
loosely paralleled by functional boundaries. However, lobar termi-
nology is so ﬁ  rmly embedded in clinical and non-clinical neuro-
science that consideration of their anatomical features is essential.
(a) The frontal lobe (Fig. 2.3.1.2)
The precentral gyrus, immediately in front of the central sulcus 
and continuing onto the medial surface, contains the primary 
motor cortex. The precentral sulcus usually deﬁ  nes the anterior

motor cortex. The precentral sulcus usually deﬁ  nes the anterior 
boundary, and in front of this lies the premotor cortex. The inferior 
Fig. 2.3.1.2 Motor areas of the frontal lobe: TP , temporal pole; PHG, parahippocampal gyrus; FEF, frontal eyeﬁ  elds.Fig. 2.3.1.1 The lobes of the cerebral cortex.
Frontal
FrontalParietal
ParietalOccipital
OccipitalTemporal
Temporal(a)
(b)2.3.1 neuroanatomy

SECTION 2  the scientific basis of psychiatric aetiology 146
margin of the sulcus runs into the pars triangularis, which includes 
Broca’s motor speech area. On the medial margin and surface, the cortex includes the supplementary motor area. The lateral prefron-tal cortex, in front of these motor and associated areas, is usually grooved by two major horizontal sulci, deﬁ  ning the superior, mid-
dle, and inferior frontal gyri. The cortex on the medial surface of the frontal lobe anterior to the prefrontal gyrus forms the medial prefrontal cortex. The concave inferior surface of the frontal lobe, overlying the bony orbit in vivo , is the orbitofrontal cortex.
(b) The parietal lobe (Fig. 2.3.1.3)
Behind the central sulcus, the primary somatic sensory cortex (SI),

Behind the central sulcus, the primary somatic sensory cortex (SI), 
extending onto the medial surface to occupy the posterior part of the paracentral lobule, where the sacral spinal segments are repre-sented, occupies the postcentral gyrus. The postcentral sulcus lim-its the postcentral gyrus posteriorly. Behind this, the sulcal pattern is variable, but one or more horizontal intraparietal sulci divide the lobe into superior and inferior parts. The second somatic sensory cortex (SII) is located in the parietal operculum, close behind the inferolateral tip of the central sulcus. Speciﬁ  c sulcal patterns in the 
transition region between the parietal lobe and the occipital and temporal lobes (the supramarginal and angular gyri) are important landmarks for the detailed localization of language functions.
(c) The occipital lobe (Fig. 2.3.1.4)

The occipital lobe is predominantly involved in vision and visual perception. The medial surface is grooved by the deep horizontal calcarine sulcus, which typically reaches the posterior pole of the hemisphere. Within its walls is the primary visual cortex. This area 
(area 17 of Brodmann) is often called the striate cortex; in the freshly sliced brain, a thin band of white matter, the stria of Gennari, is clearly visible running in the centre of the cortical grey ribbon. The extent of this stria precisely demarcates the primary visual cortex. Surrounding areas of the medial and lateral surface, the prestriate and peristriate cortex, contain some of the numerous separate visual association areas.
(d) The temporal lobe (Figs 2.3.1.5 and 2.3.1.6)

Two horizontal sulci, the superior and inferior temporal sulci, divide the lateral surface of the temporal lobe into the superior, middle, and inferior gyri. The latter, extending onto the inferior surface, is also known as the inferotemporal cortex. On the medial surface, the collateral sulcus runs from close to the temporal pole to the calcarine sulcus posteriorly. Medial to this is the parahippoc-ampal gyrus. Anteriorly, this curves dorsally and caudally to form the hook-shaped uncus. The entorhinal cortex occupies approxi-mately the anterior third of the parahippocampal gyrus. Lateral to this, in the walls of the rhinal sulcus, lies the perirhinal cortex. The uncus closely overlies the amygdala; the primary olfactory cortex, the piriform cortex, lies immediately in front. The choroid ﬁ  ssure 
limits the parahippocampal gyrus medially. Passing into the ﬂ  oor

limits the parahippocampal gyrus medially. Passing into the ﬂ  oor 
of the lateral ventricle, the subicular areas of cortex lead to the hip-pocampus proper. A detailed consideration of the anatomy of the 
hippocampus is given below.
The cortex of the temporal operculum contains Heschl’s gyri, 
within which lies the primary auditory cortex. Diverse auditory 
Fig. 2.3.1.3 (a) Areas of the parietal lobe; (b) somatic sensory association pathways. TP , temporal pole; PHG, parahippocampal gyrus; MTG, m iddle temporal gyrus.

147
Fig. 2.3.1.4 The occipital lobe: (a) visual areas; (b) visual association pathways. TP , temporal pole; IT, inferotemporal cortex;
PHG, parahippocampal gyrus; STG, superior temporal gyrus; MTG, middle temporal gyrus; Ant, anterior; Post, posterior.
Fig. 2.3.1.5 Auditory association connections. TP , temporal pole; PHG, 
parahippocampal gyrus.Fig. 2.3.1.6 Olfactory and limbic structures: (a) ventral surface of the brain;
(b) medial temporal lobe. 1, Association cortex to parahippocampal gyrus; 
2, parahippocampal gyrus to entorhinal cortex; 3, entorhinal cortex to 
hippocampus (perforant path).
2.3.1 neuroanatomy

SECTION 2  the scientific basis of psychiatric aetiology 148
association areas surround this, extending into the superior tem-
poral gyrus. The functions of the cortex of the middle temporal 
gyrus are uncertain, but include complex visual, auditory, and somatic sensory association areas. The inferotemporal cortex is largely concerned with visual perception and cognition. The ana-tomical pathways that underlie these functions are considered below.
(e) The insula
The anterior margin of the insula, where the cortex becomes con-tinuous with the anterior perforated substance, is known as the limen insulae. Above and below, where the insular cortex rolls round onto the opercula, lies the circular sulcus, the superior and inferior rami of which fuse posterosuperiorly to form the apex of the insula. Several variable sulci mark the insula, but little is known of the functional subdivisions of this cortex; gustatory, somatic sensory, and auditory areas have been described.

The structure of the neocortex
The neocortical grey matter is usually described as having six layers (Plate 1(a)). Wide variation in the nature of this microscopic lamina-tion underlies the subdivision of neocortex into a multiplicity of (usually numbered) areas. At its simplest, two types of neurones make up the grey matter—pyramidal and non-pyramidal (or granu-lar) cells. An apparent predominance of one or other type gives the 
extremes of granular and agranular cortex, equating with sensory 
areas (granular) and the motor cortex (agranular). In fact, the pro-portion of different cell types is constant in all areas. Indeed, with the single exception of the primary visual cortex, the numbers of neu-rones under a ﬁ  xed surface area is also constant in all cortical areas. 
Variations in the size of pyramidal cells in particular lead to an appar-ent change in proportions. These variations probably reﬂ  ect differ-
ences in the axonal volume of individual pyramidal cells, reﬂ  ecting

ences in the axonal volume of individual pyramidal cells, reﬂ  ecting 
the distance and volume of projection ﬁ  bres from a cortical area.
Pyramidal cells have a single main apical dendrite ascending 
towards the pial surface, and several horizontally spreading basal dendrites. All dendrites bear dendritic spines, which receive syn-apses (Plate 1(b)). All pyramidal cells use excitatory amino acids as neurotransmitters and have axons which enter the subcortical white matter; hence they are all projection neurones. They consti-tute approximately 60 per cent of all the neurones in the cortex. A second spiny neuronal type, the spiny stellate cells, is the next most numerous. These also use an excitatory amino acid, most probably glutamate, as their neurotransmitter. Unlike pyramidal cells, however, their axons remain conﬁ  ned to the cortical grey

matter; they are interneurones, accounting for a further 25 per cent of cortical neurones. All the other neurones are inhibitory interneu-rones, using γ-aminobutyric acid (GABA) as their major neuro-
transmitter. Many also contain one or more neuropeptides, and their content of speciﬁ  c calcium-binding proteins varies. They have 
a wide range of axonal and dendritic forms, and have been multi-ply classiﬁ  ed in the past. Broadly speaking, they can be grouped 
into those with horizontal axonal arborizations, those whose axons 
ramify at right angles to the pial surface, i.e. through the depth of the cortex, and those with radial axons (Fig. 2.3.1.7).
The structure of the allocortex

The allocortex comprises a number of different areas, all with very different structures. They are either limbic or olfactory (or both) and are found predominantly in the medial temporal lobe. The largest of these regions is the hippocampus. Essentially, this includes the three-layered cortex of the hippocampus, together with the transitional areas between it and neocortex, which are variably said to have three, four, ﬁ  ve, or six laminae. The hippocampal formation comprises the 
dentate gyrus, Ammon’s horn (CA ﬁ  elds), and the subiculum. Both 
the dentate gyrus and the CA ﬁ  elds have a prominent single layer of 
neurones, with an overlying molecular layer and a subjacent poly-morphic layer.  In the dentate gyrus, the cells are granule cells, whereas in the CA ﬁ  elds they are predominantly large pyramidal cells—the

stratum pyramidale. Both cell types are excitatory and are projection neurones. Scattered populations of GABA-ergic inhibitory interneu-rones are found immediately subjacent to the main cellular laminae and in the molecular layers. The CA ﬁ  elds are numbered 1, 2, and 3, 
from the subiculum to the dentate gyrus. The subiculum is the zone of transition between the three-layered hippocampus proper, and the entorhinal cortex and cortex of the parahippocampal gyrus laterally. It is sometimes further subdivided into subzones including the pre-subiculum, between the lateral cortex and the subiculum, and the prosubiculum, between the subiculum proper and CA1 of the hip-pocampus. The histological appearance of the hippocampus and adjacent areas are shown in Fig. 2.3.1.8, and their connections are considered in detail below.
Fig. 2.3.1.7 Inhibitory (GABA-ergic) neurones of the neocortex: (a) vertical; 
(b) horizontal.

149
The general pattern of connectivity of the cortex
All cortical areas share a broadly similar pattern of connections. 
What differs is the relative quantity of connections in each category, 
as well as the precise detail of origin and termination. The broad 
categories of connections which all cortical areas share are most 
easily seen in a table (Table 2.3.1.1). These will be dealt in detail in 
subsequent sections.
A central feature of the connections of the neocortex is their 
organization relative to the cortical laminae (Plate 1(a)). For sim-
plicity, it can generally be assumed that the forward-ﬂ  owing stream 
of connections for perception and action use the central laminae, 
descending projections originate in deeper layers, and feedback 
and non-speciﬁ  c afferents terminate in both superﬁ  cial and deep 
laminae. Thus, in primary sensory areas the thalamic input from 
the principal nuclei (e.g. the lateral geniculate nucleus in the visual

the principal nuclei (e.g. the lateral geniculate nucleus in the visual 
cortex) terminates in layer IV . Projections to higher association 
areas originate from pyramidal cells immediately adjacent, in 
layer III. As the ipsilateral association pathway progresses from area 
to area, the association ﬁ  bres terminate in this central region, and 
the thalamic afferents end in superficial and deep laminae. 
Projections to subcortical nuclei, such as the striatum, arise in 
layer V , and corticothalamic axons come from layer VI. It is as if 
the input of major importance, requiring detailed, focused, and 
faithful transmission, arrives in layer IV and is passed on from the 
deeper part of layer III. Inputs which moderate or modulate this 
pass to either side of the central layers, and outputs which are not 
directly part of this progression arise from deeper layers.Fig. 2.3.1.8 (a) Hippocampal

directly part of this progression arise from deeper layers.Fig. 2.3.1.8 (a) Hippocampal 
formation in the temporal lobe; (b) 
subdivisions of the hippocampal 
formation; (c) organization of the 
hippocampus.
Table 2.3.1.1 General connections of the cerebral cortex
Nucleus/area Afferents Efferents
Subcortical
Thalamus
 Principal
 Intralaminar
Locus coeruleus (NA)
Raphe (serotonin)
Basal nucleus (ACh)
Hypothalamus (histamine)
SN and VTA (dopamine)
Claustrum
Striatum
Pons
Superior colliculus and reticular formation
Speciﬁ  c (e.g. corticospinal)+
+
+
+
+
+
+
+
−
−
−
−+
+
−
−
−
−
−
+
+
+
+
(+/−)
Cortical
Contra lateral
 Homotopic
 Heterotopic
Ipsilateral
 Short
 Long+
+
+
++
+
+
+
NA, noradrenaline; ACh, acetylcholine; SN, substantia nigra; VTA, ventral tegmental area.2.3.1 neuroanatomy

SECTION 2  the scientific basis of psychiatric aetiology 150
There is a general principle in the organization of connectivity 
with the cerebral cortex of overlapping connectivity of functionally 
related areas throughout the range of connections made. In other words, functionally related cortical areas, which are connected with each other, also tend to have overlapping or interdigitating connections with other structures. This is seen on the striatum, the thalamus, the claustrum, the cholinergic basal forebrain, and the pontine nuclei.
Subcortical afferents to the cerebral cortex
The thalamus (Plate 2)
Thalamic nuclei can be classiﬁ  ed as speciﬁ  c (principal) or non-
speciﬁ  c. In general, the speciﬁ  c nuclei degenerate completely when 
the cortex is removed, whereas the non-speciﬁ  c nuclei do not. This 
is because the sole major projection of the speciﬁ  c nuclei is to the

is because the sole major projection of the speciﬁ  c nuclei is to the 
cerebral cortex. The non-specific nuclei are the intralaminar and midline nuclei, which project to the basal ganglia as well as to cortex, and the reticular nucleus, which projects only to other thalamic nuclei.
All cortical areas receive afferents from at least one speciﬁ  c 
thalamic nucleus, and an additional input from the intralaminar/midline nuclei. Corticothalamic ﬁ  bres reciprocate all thalamocort ical
projections, probably without exception.
(a) Speciﬁ  c nuclei
The cortical projections of the speciﬁ  c nuclei are shown in Plate 2. 
Subclassiﬁ  cation of the speciﬁ  c thalamic nuclei depends upon their

Subclassiﬁ  cation of the speciﬁ  c thalamic nuclei depends upon their 
afferent subcortical connections. The primary relay nuclei receive the major sensory pathways—the lateral and medial geniculate nuclei for the optic tract and auditory pathway respectively, and the ventral posterior nucleus for the somatic sensory pathways. 
The secondary relay nuclei are those which receive a known major subcortical pathway which is not sensory. These are usually taken to include the caudal subdivision of the ventral lateral nucleus, which receives the cerebellar pathway, the anterior division of the ventral lateral nucleus and the ventral anterior nucleus, which both receive ﬁ  bres from the internal segment of the globus pallidus, and 
the anterior nuclei, which receive the mammillothalamic tract. The 
association nuclei are those which were not previously understood

association nuclei are those which were not previously understood 
to receive a major subcortical pathway, predominantly the medial nucleus and the pulvinar. This view is no longer really tenable, since 
the pulvinar is now known to receive a major input from the supe-
rior colliculus, and the various subdivisions of the medial nucleus receive ﬁ  bres from the ventral pallidum and the olfactory pathway, 
amongst others. The subcortical afferents to the principal thalamic 
nuclei are shown in Plate 2(a).
(b) The non-speciﬁ  c nuclei
The reticular nucleus lies lateral to the main body of the thalamus, 
separated from it by the external medullary lamina. Cells in the 
nucleus are inhibitory, using GABA as their neurotransmitter. 
Excitatory thalamocortical and corticothalamic ﬁ  bres, passing to

Excitatory thalamocortical and corticothalamic ﬁ  bres, passing to 
and from the main nuclei, traverse the reticular nucleus and give axon collaterals to the reticular nucleus cells. There is a very tight 
arrangement, whereby the branches of axons from the thalamus to 
a particular cortical area terminate in the reticular nucleus in close proximity to the corticothalamic axons from the same cortical area. The reticular nucleus cells in turn send their inhibitory axons into the thalamus, to terminate precisely in the nuclei from which they 
receive a collateral input.
The intralaminar and midline nuclei receive afferents from the 
major pathways to their adjacent principal nuclei and project tothe striatum (caudate, putamen, and ventral striatum) as well as to 
the cortex. There is a broad topographic relationship in their projec-

tion to both areas. The midline nuclei innervate the ventral striatum (nucleus accumbens) and the limbic cortex, including the hippoc-ampal formation. The anterior intralaminar nuclei connect with the 
prefrontal, parietal, occipital, and temporal cortex, and project to all 
parts of the caudate. The posterior intralaminar nuclei, of which the 
centromedian nucleus is the largest, project to the putamen and are reciprocally related to the motor, premotor, and supplementary 
motor areas of cortex in the frontal lobe. Many axons to the cortex from the intralaminar nuclei are collateral branches of thalamostri-ate axons. The cortical and striatal areas to which they each project 
are precisely those parts of the cortex and striatum which are them-selves directly connected by corticostriate ﬁ  bres.
Non-thalamic subcortical afferents to the 

A variety of nuclei send afferents to the cerebral cortex. These fall 
into two categories: ﬁ  bres from the so-called isodendritic core of 
the brainstem and basal forebrain, which are non-reciprocal and 
aminergic, and the two-way interconnections with the claustrum.
Acetylcholine and the basal forebrain
A system of cholinergic nuclei extend from the septum verum ante-riorly, through the nuclei of the diagonal band of Broca to the basal 
nucleus of Meynert in the substantia innominata, ventral to the 
globus pallidus, most posteriorly. From these, cholinergic ﬁ  bres 
pass to the entire cerebral cortex. Alternative nomenclature for these nuclei uses a numeric system, (Ch1 to Ch4). The anterior cell 
groups project to the hippocampus and entorhinal cortex, and to

groups project to the hippocampus and entorhinal cortex, and to 
the olfactory bulb and cortex. There is an approximate topographic 
relationship in the projection of the basal nucleus to the neocortex, but with considerable overlap; adjacent or overlapping regions of the nucleus project to widely separated but functionally related and 
interconnected areas of neocortex. Degeneration of this system is associated with the dementias of Alzheimer’s disease and Lewy 
body disease.
Cholinergic cells in the pedunculopontine nucleus of the mid-
brain project to the thalamus, particularly to the midline and 
intralaminar nuclei.
(a)  Serotonin, noradrenaline (norepinephrine) and adrenaline 
(epinephrine): the raphe and associated nuclei
The median group of nuclei of the brainstem reticular formation is

The median group of nuclei of the brainstem reticular formation is 
made up largely of the various raphe nuclei, all of which use serot-
onin (5-hydroxytryptamine) as their neurotransmitter. Their 
projections are very widespread throughout the central nervous 
system. Broadly speaking, there is a rostrocaudal topography to the 
efferent projections of these nuclei. The most rostral, notably the 
dorsal median raphe nucleus in the midbrain tegmentum, send 
projections to the entire cerebral cortex and striatum. There is a prominent projection to the thalamus, notably to the midline 
nuclei which in turn project in part to the hippocampal formation.

151
The serotoninergic raphe-spinal tract, which has important func-
tions in the gating of pain, arises from the most rostral nuclei, the raphe obscurus and the raphe magnus.
The locus coeruleus lies in the dorsolateral pons, immediately 
deep to the ventricular ependyma. T ogether with the subceruleus 
immediately deep to it, this nucleus supplies noradrenergic ﬁ  bres 
to most of the central nervous system. Ascending ﬁ  bres pass to the 
thalamus and hypothalamus, the entire cerebral cortex (neo- and allocortex), the amygdala, the septal nuclei, and the olfactory bulb. Adrenergic cells in the brainstem do not appear to send ascending projections to the cortex.
(b) Dopamine: the substantia nigra and adjacent nuclei

The major dopaminergic cell group of the midbrain is the pars compacta of the substantia nigra, which projects to the striatum (caudate, putamen, nucleus accumbens, and olfactory tubercle). Two other adjacent nuclei, the ventral tegmental area of Tsai and the pigmented parabrachial nucleus, are also dopaminergic. 
T ogether, these three cell groups project rostrally in the medial 
forebrain bundle to innervate the thalamus and hypothalamus, 
the hippocampal formation, the entorhinal cortex and amygdala, 
and widespread areas of the neocortex, especially the prefrontal, orbitofrontal, and cingulate cortex.
(c) Histamine and the posterior hypothalamus
The entire cerebral cortex, including the limbic lobe, receives a histaminergic projection from the tuberomamillary nucleus of the posterior hypothalamus. Postsynaptic receptors appear to be of 
two types, H1 and H2, with broadly opposing effects.
(d) The cortex and the claustrum

The claustrum is a thin plate of grey matter lying immediately deep to the cortex of the insula, and separated from it by the white 
mat
ter of the extreme capsule. Medially, the external capsule 
(Fig. 2.3.1.8(a)) separates it from the putamen. The nucleus receives ﬁ bres from and projects to the whole cortex, including the allocor-
tex. The reciprocal connection is topographically organized, but with overlapping zones projecting to widely separated but func-tionally related and interconnected cortical areas. Many of the neurones of the claustrum have branching axons with collaterals going to two or more such interconnected areas. For example, the superior parietal cortex (area 5) is widely separated from the pre-motor cortex (area 6) but is connected to it by ipsilateral associa-tion ﬁ  bres, and the two areas are functionally closely related. Both

these areas project to and receive from an overlapping zone of the claustrum, and many axons of claustral cells in this zone may branch to both areas.
(e)  Modulation of cortical activation and the anatomy of the 
reticular activating system
Speciﬁ  c information to the cerebral cortex, for example relating to 
sensory stimuli in the periphery, is relayed via the main thalamic nuclei. The other, diffusely projecting, systems are most likely to be involved in the regulation of cortical responsivity. Such a role has been demonstrated electrophysiologically for the claustrum, and the pharmacology of the antihistamines indicates a role for this trans-mitter system in the regulation of cortical arousal. The cholinergic input from the basal forebrain is necessary for the proper function-ing of the cortex, and its degeneration is associated with cognitive decline and memory impairment. The possible relationship of mesolimbic dopamine pathways to schizophrenia is well known.

Similarly, the psychopharmacology of serotonin also implies a major role for this transmitter system in the proper functioning of the cortex. There are two routes by which these ‘non-speciﬁ  c’ path-
ways affect the cortex: direct projections, and an indirect pathway through the thalamus. Brainstem nuclei send ﬁ  bres to the intrala-
minar and midline nuclei, which in turn send ﬁ  bres to the entire 
cortex including the hippocampus. The cholinergic input from the interpeduncular nucleus to the intralaminar nuclei is prominent. Serotonin is particularly concentrated in the midline nuclei. There are other reticular formation projections to these nuclei, but the transmitters remain uncertain. This latter indirect route by which the reticular formation of the brainstem impinges on the cerebral cortex via the thalamus constitutes the reticular activating system. The role of this system in cortical arousal is well documented.
Corticocortical connections

(a)  The corpus callosum and the commissural connections of 
the cerebral cortex
All cortical areas, both send ﬁ  bres to and receive ﬁ  bres from the 
opposite hemisphere, although the connections are not necessarily throughout the whole area. In most of the cortex, commissural ﬁ bres pass to the contralateral side in the corpus callosum. The 
anterior commissure carries ﬁ  bres that interconnect the anterior 
third or so of the temporal lobe with its partner, as well as ﬁ  bres 
that interconnect the olfactory bulbs on each side. Some ﬁ  bres in 
the fornix cross the midline, the so-called commissure of the for-nix, to interconnect the two hippocampal formations. Commissural ﬁ bres are of two types, homotopic and heterotopic. Homotopic 
ﬁ bres pass from one area of cortex to the same area on the other side. 
Heterotopic ﬁ  bres pass from one area to a different, although, often

Heterotopic ﬁ  bres pass from one area to a different, although, often 
functionally related, area on the other side. As a generalization, the functions of the commissures can be subdivided into two 
categories. First, they serve to interconnect representations of the 
contralateral sensory surround across the midline, for example, the representations of the two halves of the body, the two visual hemi-ﬁ elds, and so on. In areas containing a lateralized sensory represen-
tation, of either the body or the visual ﬁ  eld, the callosal ﬁ  bres are 
conﬁ  ned, in both origin and termination, to the parts of the area 
containing a representation of midline and adjacent regions. Thus the representation of the trunk in somatic sensory areas sends and receives commissural ﬁ  bres, whereas the hand and foot representa-

tions are not connected across the midline. Similarly, the vertical meridians in visuotopic representations are interconnected by callosal ﬁ  bres, whereas the periphery is not. In contrast, the second 
function of the commissures is to connect areas in one hemisphere with areas on the other side, where the functions of each are repre-sented on only one side, i.e. they are lateralized. Of course, this is most apparent for language areas; for example, objects held in the non-dominant hand cannot be named following callosal section because the sensory cortex of the non-dominant hemisphere can-not communicate across the midline with the language and speech areas in the dominant hemisphere.
(b) Ipsilateral corticocortical association connections
All cortical areas interconnect with other areas in the same hemi-sphere. The primary sensory areas are in the parietal, occipital, and temporal lobes. From these, parallel pathways emanate in an 2.3.1 neuroanatomy

SECTION 2  the scientific basis of psychiatric aetiology 152
approximately hierarchical sequence through multiple areas in the 
adjacent association cortex, passing towards the medial temporal lobe where all pathways converge on the parahippocampal gyrus and the cortex of the temporal pole. In general, three ‘tiers’ of asso-ciation areas can be recognized in this sequence; the ﬁ  rst tier receives

from the core sensory areas, and the third projects into the tempo-ral pole and the parahippocampal gyrus. Connections passing in the direction of the medial temporal cortex from the primary sensory areas have a feedforward pattern of termination, whereas the reciprocal connections have a feedback character. Although the interconnections of the multiple areas along this sequence of con-nections are complex, a broad pattern common to all the sensory pathways can be discerned. Essentially, each sensory modality has a core zone in the cortex, comprising three areas. Each of these is linked to the relevant main thalamic nuclei and contains a com-plete representation of the sensory surround. They are linked together by short association connections passing forwards from the ﬁ  rst thalamo-recipient zone in a stepwise fashion to the other

two. Two streams of connections, dealing with different aspects of sensory perception, emanate from these into the surrounding association areas. One of these, the ventral stream (the ‘stimulus-relevant’ or ‘what’ system), is primarily concerned with a detailed perception and characterization of the  stimulus. The second, the dorsal stream (the ‘self-relevant’ or ‘where’ system), is concerned mainly with spatial location, particularly in extrapersonal space. Each area in this sensory hierarchy is reciprocally connected to a part of the frontal lobe, where the dual-pathway streams are repre-sented by a dorsal and a ventral prefrontal subdivision, feeding onto the supplementary and premotor cortex, and so to the motor cortex.
(c) Cortical association pathways for vision (Fig. 2.3.1.4)

The three core visual areas are V1 (the primary visual cortex, striate cortex), V2 which surrounds V1 and is contained within Brodmann’s area 18, and outside this the V3 complex which is probably still within area 18. From these, feedforward projections pass to areas in the inferior parietal and superior temporal cortices, as the dorsal stream, and to V4, within Brodmann’s area 19, at the junction of the occipital association cortex with the inferior tem-poral gyrus on the medial surface, forming the ventral pathway. Areas in the superior temporal sulcus and middle temporal gyrus form the next two tiers of association cortex for the dorsal pathway. The ventral route progresses via the posterior inferotemporal cor-tex on to the anterior inferotemporal cortex. Both the anterior inferotemporal and middle temporal cortical areas at the distal end of these two visual association pathways project to the cortex of the

temporal pole, and to the parahippocampal gyrus. The parahip-
pocampal gyrus projects to the entorhinal cortex more anteriorly, and the temporal pole connects with the amygdala. The entorhinal cortex provides a major input to the dentate gyrus of the hippoc-ampus via the perforant path as seen in the ﬁ  gure. Similarly, the 
amygdala projects into the hippocampal formation.
(d)  Cortical association pathways for somatic sensation 
(Fig. 2.3.1.3)
The three core areas for the somatic sensory cortex are Brodmann’s 
areas 3, 1, and 2 on the postcentral gyrus, together constituting the classical primary somatic sensory cortex. Each receives a major input from the ventral posterior nucleus of the thalamus and con-tains a complete representation of the body. Area 3 projects forwards to areas 1 and 2, and area 1 projects similarly to area 2. All three 
areas project in a feedforward fashion to the second somatic sen-sory area in the parietal operculum. This represents the ﬁ  rst step on

areas project in a feedforward fashion to the second somatic sen-sory area in the parietal operculum. This represents the ﬁ  rst step on 
the ventral association pathway. The dorsal pathway begins with the projection of all subdivisions of the primary somatic sensory cortex to Brodmann’s area 5 in the superior parietal cortex. Further steps along the ventral pathway are areas in the insula. In the ven-tral pathway, information ﬂ  ows from the superior to the inferior 
parietal cortex, and so to the middle temporal gyrus. Areas at the ends of both these paths project onto the parahippocampal gyrus and the temporal pole.
(e) Cortical association pathways for hearing (Fig. 2.3.1.5)

The association pathways from the auditory cortex are less well understood. The three core areas lie along Heschl’s gyrus in the temporal operculum, with the classical primary auditory area (AI) most posterior, the rostral auditory area (AII) more anterior, and the rostrotemporal auditory area in front of that. Each of these contains a complete representation of the auditory surround, organized tonotopically, and connects with the medial geniculate nucleus. On either side of these lie multiple auditory association areas, termed the medial and lateral belt areas, representing the ﬁ  rst 
steps along the two association streams of connections, although it is unclear which is ‘dorsal’ and which is ‘ventral’ in a functional sense. The medial belt areas have connections with parts of the insula, whereas the lateral belt areas project into the association cortex of the superior temporal gyrus. The ﬁ  rst association path-

way probably continues through areas of the anterior part of the 
superior temporal gyrus, and so to the parahippocampal gyrus and the temporal pole. The second continues from the superior to the middle temporal gyrus, and thence to the parahippocampal cortex and the temporal pole.
(f ) The olfactory pathway to the cerebral cortex (Fig. 2.3.1.6)
The olfactory pathway is unique among the sensory modalities in having direct access to the cerebral cortex without passing through the thalamus. The primary olfactory receptor neurones of the olfactory mucosa send their axons (the ﬁ  la olfactaria) through the

cribriform plate of the ethmoid bone directly into the overlying olfactory bulb, where they contact the mitral cells in synaptic glomeruli. Axons of the mitral cells pass caudally in the olfactory tract to the anterior perforated substance. Here the olfactory tract splits into medial and lateral olfactory striae. All the mitral cell axons pass in the lateral stria. The medial stria contains axons mainly from the anterior olfactory nucleus, which are destined for the contralateral olfactory bulb by way of the anterior commissure. The lateral olfactory stria passes to the medial temporal lobe, where the axons terminate in the anterior margin of the entorhinal cor-
tex, the pyriform cortex, and the corticomedial subdivision of the

tex, the pyriform cortex, and the corticomedial subdivision of the 
amygdala. All three termination zones interconnect. The olfactory entorhinal cortex and the olfactory amygdala both have connec-tions with their non-olfactory partners, i.e. with the more posterior entorhinal subdivisions and the basolateral part of the amygdala respectively.
(g) The limbic cortex and the amygdala (Figs 2.3.1.6 and 2.3.1.8)
The latter stages of the sensory association pathways all converge on the entorhinal cortex, the perirhinal cortex, and the amygdala, which are themselves interconnected. These in turn project to the hippocampus. The perirhinal cortex lies lateral to the entorhinal

153
cortex in the banks of the rhinal ﬁ  ssure. It appears to receive 
afferents from the later stages of the sensory association pathways, 
notably from the temporal pole, and is extensively interconnected 
with the amygdala, the entorhinal cortex, and the hippocampus. 
The amygdala projects to the CA pyramidal cells, notably to CA1. 
The entorhinal input to the hippocampus arises from cell clusters 
in layer II and forms the perforant pathway, with axons terminat-
ing on the dendrites of granule cells of the dentate gyrus. Additional 
entorhinal ﬁ  bres pass to the CA pyramidal cells. Axons of the 
dentate gyrus granule cells pass out into the molecular layer of the 
CA ﬁ  elds, notably CA3, where they synapse on the apical dendrites 
of pyramidal neurones. CA3 pyramidal cells project out via the 
ﬁ mbria, but also send collateral axons to synapse with the pyrami-
dal cells of CA1 in particular. The activity of pyramidal neurones in

dal cells of CA1 in particular. The activity of pyramidal neurones in 
the CA ﬁ  elds is regulated by inhibitory GABA-ergic interneurones 
in the molecular layer and by the basket cells, which are also GABA-
ergic, sited immediately subjacent to the pyramidal layer. The latter 
inhibitory neurones have axons that branch around the pyramidal 
cell bodies, forming the baskets of terminal ﬁ  bres from which they 
are named. CA1 sends some ﬁ  bres into the fornix, but projects 
heavily to the subicular complex. The major output of the hippoc-
ampal formation comes from the subicular complex, and passes 
out into the fornix via the alveus and ﬁ  mbria. The projection of 
ﬁ bres in the fornix to the hypothalamus, including the mamillary 
nuclei, is considered below. However, some hippocampal efferent 
ﬁ bres bypass these nuclei and enter the mamillothalamic tract

ﬁ bres bypass these nuclei and enter the mamillothalamic tract 
without synapsing. Rather they pass directly to the anterior 
thalamic nuclei, where they terminate. From the anterior thalamic 
nuclei, of which there are several subdivisions, axons project to the 
cortex of the cingulate gyrus along the whole of its length, extend-
ing into the parahippocampal gyrus inferiorly. Fibres forming the 
cingulum bundle interconnect these medial cortical areas, running 
predominantly from anterior to posterior and ending in the para-
hippocampal gyrus, so that they reach the entorhinal cortex. This 
completes Papez’s circuit and deﬁ  nes the structures of the limbic 
lobe—hippocampal formation, mamillary nuclei and anterior 
thalamus, cingulate cortex, parahippocampal gyrus and cingulate 
cortex. The term ‘limbic system’ is often extended to include struc-

tures, such as the amygdala, which have strong connections with 
these components.
(h) Association connections of the frontal lobe (Fig. 2.3.1.2)
The hierarchical sequence of connections in the sensory associa-
tion pathways outlined above is reﬂ  ected in a similar sequence 
passing from association areas of the prefrontal cortex back towards 
the primary motor cortex of the precentral gyrus. The two streams 
of connections are tightly linked together by long association 
pathways, with each tier of connections in the sensory association 
pathways interconnected with an area of the frontal lobe. The 
medial temporal areas, including the entorhinal cortex, the perirhi-
nal cortex and the parahippocampal gyrus are closely intercon-

nected with areas in the orbitofrontal cortex. The temporal pole is 
reciprocally connected with the frontal pole (Brodmann’s area 10). 
The tiers of sensory association areas in the parietal, occipital, 
and temporal cortex are interconnected with the dorsolateral and 
ventrolateral prefrontal association cortex, occupying Brodmann’s 
areas 9, 46, and 45. Broadly speaking, the association areas on the 
dorsal stream of connections for each modality interconnect with 
the dorsolateral prefrontal areas 9 and 46. In contrast, the ventral stream areas interconnect with the ventrolateral prefrontal cortex 
in areas 45 and 46. Like the sensory association areas, these regions 
seem to separate functionally into a dorsal hierarchy, dealing with

seem to separate functionally into a dorsal hierarchy, dealing with 
internally generated actions, and a ventral hierarchy related to 
externally guided behaviours. Connections from the dorsolateral 
prefrontal cortex pass preferentially to the supplementary motor 
cortex, whereas the more ventrally placed prefrontal cortex feeds 
into the premotor cortex. Both the supplementary and the premo-
tor cortex feed into the primary motor cortex of the precentral 
gyrus. The frontal eye-ﬁ  eld (Brodmann’s area 8), which has major 
ipsilateral association connections with the visual areas in the 
occipital lobe, is strategically placed between the prefrontal and 
premotor areas. It also receives ipsilateral association connections 
from the dorsolateral and ventrolateral prefrontal association 
areas.
(i) Speech areas of the cerebral cortex
Because speech and language are not present in the subhuman

areas.
Because speech and language are not present in the subhuman 
primate species commonly used for neuroanatomical investigation 
of cortical connections, little is known about the connections of 
these in the human. The posterior speech area (Wernicke’s area) 
occupies a large extent of the posterior temporal and inferior 
parietal cortex at the posterior limits of the superior temporal and 
lateral sulci, and is often taken as extending anteriorly along the 
superior temporal gyrus. It includes the angular and supramarginal 
gyri (Fig. 2.3.1.9). This would represent a region where the associa-
tion pathways of all three modalities—somatic sensation, vision, 
and hearing—lie close together. It would include many auditory 
association areas along the superior temporal gyrus. Within the 
frontal lobe, Broca’s area occupies the pars triangularis between the

frontal lobe, Broca’s area occupies the pars triangularis between the 
anterior and ascending rami of the lateral sulcus. It is closely 
adjacent to the face area in the lateral premotor cortex. Similarly, 
the medial speech area lies on the medial surface immediately in 
front of the face representation in the supplementary motor cortex. 
It is, perhaps, not unreasonable to suppose that these two areas 
function to some extent as the premotor and supplementary motor 
speech areas.
Fig. 2.3.1.9 Auditory association cortex and Wernicke’s sensory speech area.

SECTION 2  the scientific basis of psychiatric aetiology 154
Subcortical efferent pathways of the 
The corticostriate pathway and the basal 
ganglia (Fig. 2.3.1.10)
The anatomical deﬁ  nition of the basal ganglia comprises those 
deep grey matter nuclei that develop from the telencephalic (cere-
bral) vesicle. Strictly, this would include the components of the 
striatum, the globus pallidus, the amygdala, and the claustrum. 
Because these latter two are better considered with the cortex 
and limbic system respectively, they are usually excluded from the 
term basal ganglia. Similarly, because of their close anatomical and 
functional relationship with the striatum and globus pallidus, the 
substantia nigra and subthalamic nucleus are usually included with 
the basal ganglia. The caudate and putamen are developmentally, 
anatomically, pharmacologically, and functionally a single struc-
ture, secondarily subdivided by the development of the internal

ture, secondarily subdivided by the development of the internal 
capsule. The two fuse below the inferior margin of the anterior 
limb of the internal capsule to form the nucleus accumbens. This 
fusion comes to the surface of the hemisphere at the anterior perfo-
rated substance, an area sometimes called the olfactory tubercle. 
T ogether, the caudate, putamen, nucleus accumbens, and olfactory 
tubercle make up the striatum. The globus pallidus consists of two 
parts, an external segment (GPe) and an internal segment (GPi), 
separated by a thin white-matter lamina. Both segments extend 
ventrally in the region of the substantia innominata, below the 
anterior commissure, to form the ventral pallidum. The pars retic-
ulata of the substantia nigra (SNpr) is developmentally, anatomically, pharmacologically and functionally a part of the internal

ulata of the substantia nigra (SNpr) is developmentally, anatomically, pharmacologically and functionally a part of the internal 
segment of the globus pallidus, which has been separated off by 
the development of the ﬁ  bres of the internal capsule passing into 
the crus cerebri of the midbrain. Therefore, in this account the basal 
ganglia and related nuclei will comprise the striatum, GPe, GPi-
SNpr, and the subthalamic nucleus (see Fig. 2.3.1.10).
The entire cerebral cortex projects to the striatum. The putamen 
receives predominantly from the sensorimotor cortex around the 
central sulcus. The caudate receives the input from most of the 
parietal, occipital, temporal, and frontal lobes. The limbic areas, 
including the entorhinal and perirhinal cortex, the hippocampus, 
and the amygdala, project to the ventral striatum (nucleus 
accumbens and olfactory tubercle) and the adjacent ventral por-

tion of the head of the caudate. The corticostriate pathway arises 
from pyramidal cells predominantly in layer V of the cortex and is 
excitatory, using glutamate as its neurotransmitter. The termina-
tion of the pathway is broadly topographically organized, but with 
considerable interdigitation or overlap of the projections from 
different cortical areas. Individual cortical areas project to a longi-
tudinal strip of striatum orientated anteroposteriorly. The strips 
receiving from the frontal lobe extend more rostrally, whereas those 
receiving from the parietal, occipital, and temporal lobes extend 
more caudally. Anteriorly, zones receiving projections from 
interconnected areas in the frontal lobe interdigitate or overlap; 
centrally, zones receiving from frontal areas overlap with zones

centrally, zones receiving from frontal areas overlap with zones 
connected to areas within the parietal, temporal, or occipital cortex 
with which the frontal areas are connected by ipsilateral association 
ﬁ bres. More posteriorly, interconnected sensory association areas 
Fig. 2.3.1.10 The corticostriate pathway and the basal ganglia: (a) component nuclei of the basal ganglia; (b) striatum;
(c) major pathways through the basal ganglia. GPe, external segment of the globus pallidus; STN, subthalamic nucleus; GPi, 
internal segment of the globus pallidus; SNpr, pars reticula of the substantia nigra.

155
project to overlapping zones in the striatum. The striatum itself is 
compartmentalized, on the basis of acetylcholinesterase (AChE) histochemistry, into AChE-poor patches (striosomes) and AChE-rich matrix. The cortex projects into both compartments, but with a slightly different laminar origin. Pyramidal neurones in the deeper part of lamina V project to the patches, whereas more super-ﬁ cial lamina V cells and some lamina III cells project to the matrix.

It is possible that apparently overlapping corticostriate projections from different cortical areas are segregated into the different compartments. The projection from a single cortical area may switch between compartments along the anteroposterior length of its zone of termination. The intralaminar nuclei of the thalamus sends excitatory (glutamatergic) axons to the entire striatum. The nuclei project to those parts of the caudate or putamen which receive from the cortical areas and to which the particular intrala-minar nucleus projects. Many, if not all, interconnected areas in the frontal, parietal, occipital, and temporal lobes also receive a shared projection from a single intralaminar nucleus. Thus, there is a tightly organized but complex topographical relationship between the connections of functionally related cortical areas with each other, with the striatum, and with the intralaminar nuclei of the thalamus. A closely similar relationship is seen in the cortical con-nections

of functionally related cortical areas with each other, with the striatum, and with the intralaminar nuclei of the thalamus. A closely similar relationship is seen in the cortical con-nections of the claustrum and the basal forebrain, and possibly even in the cortical projection to the pontine nuclei. Another major projection to the striatum is dopaminergic and comes from the pars compacta of the substantia nigra and adjacent nuclei. There is some topography in this projection, with the lateral and central parts of pars compacta of the substantia nigra projecting to the caudate and putamen. The medial part and the adjacent nuclei, such as the ventral tegmental area, project to the ventral striatum. The effect of dopamine on striatal neurones appears to be different in the two compartments. Additional striatal afferents come from the brainstem raphe nuclei (serotonin) and the amygdala (to the ventral striatum and the head of the caudate).

The output of the striatum passes to all parts of the globus 
pallidus (the ventral pallidum, GPe, and GPi-SNpr). These ﬁ  bres 
are inhibitory, using GABA as their neurotransmitter. Here, the pathway through the basal ganglia separates into a direct and an indirect route, ultimately passing to the thalamus. Fibres from the striosomes (patches) of the striatum are rich in substance P (as well as being GABA-ergic) and project to GPi. Axons from GPi go directly to the anterior part of the ventral lateral nucleus and the adjacent ventral anterior nucleus of the thalamus, forming the direct route. Neurones in the striatal matrix compartment contain enkephalin as a cotransmitter with GABA and project to GPe. Axons from GPe go to the subthalamic nucleus, which in turn projects to GPi (the indirect pathway). The ventral pallidum has equivalent pathways, but the ﬁ  nal destination of the pallidal output

is the mediodorsal nucleus of the thalamus. All efferents from the globus pallidus are GABA-ergic and inhibitory. The neurones of the subthalamic nucleus are glutamatergic and excitatory. Activation of the striatal output through the direct pathway leads to a reduced tonic inhibition of the thalamus. In contrast, activa-tion via the indirect pathway leads to increased activation of GPi, and hence increased inhibition of the thalamus. The balance 
between these opposite effects is crucial in the normal functioning 
of the basal ganglia. Disruption of this balance is used to explain much of the pathophysiology of the extrapyramidal disorders. The ventral anterior and rostral ventral lateral nuclei of the thalamus project mainly to the premotor and supplementary motor areas 
of the frontal lobe. The ventral pallidal pathway through the mediodorsal thalamus feeds onto the prefrontal association areas. The major pathways through the basal ganglia are summarized in Fig. 2.3.1.10(c)).

The corticopontine pathway and the cerebellum
There is a major projection from the cortex to the pontine nuclei. The extent to which individual cortical areas contribute to this pathway varies. The greatest projection comes from the regions around the central sulcus, which also contribute to the pyramidal tract (see below). However, there is a substantial projection from the prefrontal cortex and a signiﬁ  cant number of ﬁ  bres from the 
occipital lobe. Many fewer corticopontine axons arise from tempo-ral neocortex, although some areas send some and it is possible that most areas send at least a few.
The pontine nuclei send their axons to the cerebellar cortex of 
the lateral parts of the posterior lobe. They terminate as mossy ﬁ bres, contacting granule cells. Axon collaterals pass, in addition, to 
the lateral dentate deep cerebellar nucleus. The anterior lobe and the midline and paramedian region of the posterior lobe are related

the lateral dentate deep cerebellar nucleus. The anterior lobe and the midline and paramedian region of the posterior lobe are related 
to the spinocerebellar inputs. The ﬂ  occulonodular lobe is connected 
to the vestibular pathway. The Purkinje cells of the cerebellar cortex send inhibitory ﬁ  bres to the deep cerebellar nuclei, and it is from 
these that the output of the cerebellum arises. The intermediate (globose and emboliform) and medial (fastigial) deep nuclei project to the red nucleus and the vestibular nuclei and reticular forma-tion. The dentate nucleus projects to the posterior part of the ven-tral lateral nucleus of the thalamus. This in turn provides the major thalamic input to the primary motor cortex of the precentral gyrus. In this way, the neocortical input to the cerebellum is transmitted via the pontine nuclei,and to the motor cortex via the thalamus.
The fornix and the cortical projection 
to the hypothalamus

Fibres leaving and entering the hippocampus form a thin white-
matter covering on the ventricular surface, deep to the ependyma, called the alveus. These ﬁ  bres pass into the fornix via the ﬁ  mbria. 
The fornix passes initially posteriorly and superiorly, then anteriorly, curving around the outer curve of the lateral ventricle and angling towards the midline in its course. The fornices of the two sides come together at about the junction of the posterior third and 
anterior two-thirds of the corpus callosum. Many ﬁ  bres pass across 
the midline, the commissure of the fornix, and turn caudally to enter the contralateral hippocampus. The two fornices, united in the midline, are suspended from the corpus callosum by the sep-
tum pellucidum as they arch over the roof of the third ventricle and the choroid ﬁ  ssure of the body of the lateral ventricle. They

tum pellucidum as they arch over the roof of the third ventricle and the choroid ﬁ  ssure of the body of the lateral ventricle. They 
turn ventrally, immediately in front of the interventricular foramen of Monroe. The two fornices separate, and each divides into an anterior and a posterior column, passing in front of and behind the anterior commissure. The anterior column carries axons to and from the septal nuclei CA3, CA1, and the subiculum project to 
the lateral septal nucleus. This has diverse efferent projections 
to the hypothalamus, the epithalamus, and the midline thalamus, but also projects to the adjacent medial septal nucleus. The medial septal nucleus is the major source of cholinergic ﬁ  bres to the hip-
pocampus via the fornix. The posterior column of the fornix curves posteriorly through the hypothalamus, giving off many ﬁ  bres to 2.3.1 neuroanatomy

SECTION 2  the scientific basis of psychiatric aetiology 156
medial and lateral hypothalamic nuclei. It ends in the mamillary 
nuclei, which in turn project via the mamillothalamic tract to the anterior thalamus. This projection is partially bilateral.
There is a major input to the hypothalamus from the amygdala, 
via the stria terminalis, a white-matter tract that follows the curve of the caudate nucleus around the lateral ventricle, lying between the caudate and the thalamus. The connections between the hypothalamus and amygdala are reciprocal.
Direct projections to the cortex from the hypothalamus have 
been discussed earlier. Direct projections from neocortex to the hypothalamus have been described, but their extent and distribu-tion are disputed. If they exist in the human, they probably arise from the prefrontal/orbitofrontal and insular cortex.
The corticobulbar and corticospinal pathways

The direct projection of the cortex to the brainstem and spinal cord, the pyramidal tract, arises from the cortex in front of and behind the central sulcus. About 40 per cent of ﬁ  bres arise from the 
primary somatic sensory cortex and the adjacent superior parietal lobe. In the frontal lobe, axons arise from the primary motor, pre-motor, and supplementary motor areas. Apart from the direct innervation of the spinal cord and motor nuclei of the cranial nerves, direct cortical ﬁ  bres innervate the red nucleus, the vestibu-
lar nuclei, the reticular formation, and the superior colliculus. In the case of the ﬁ  rst two of these, the origin of the ﬁ  bres is prob-
ably very similar to the areas of origin of the pyramidal tract. In contrast, the cortical projections to the reticular formation and superior colliculus have a much wider origin, and may include most neocortical areas to a greater or lesser degree.
The contribution of neuroanatomy

The contribution of neuroanatomy 
to psychiatry
The above is a necessarily abbreviated account of the anatomy 
of the central nervous system, centring on the organization and connections of the cortex including the limbic lobe. T opographical neuroanatomy has been ignored, despite its importance in the reading of modern images of the brain in living patients. For psy-chiatry, the importance of the connectionist view of the brain lies in the contribution it can make to the understanding of the normal and pathological functioning of the central nervous system. Present-day neuropsychology and cognitive neuroscience are aimed towards understanding the highest levels of central nervous system processing and function. It is these areas or systems that are commonly involved in the signs and symptoms of major psychiatric disease. It is to the pathways underlying cognition, perception, memory, mood, and attention that the psychiatrist interested in the

pathophysiology of mental illness must turn his or her attention, 
and it is this area that the above account has attempted to review.
Gloor, P . (1977). The temporal lobe and limbic system . Oxford University 
Press.
Pearson, R.C.A. (1995). Dorsal thalamus. In Gray’s anatomy  (38th edn) 
(ed. P .L. Williams, L.H. Bannister, M.M. Berry, et al.), pp. 1080–91. 
Churchill Livingstone, Edinburgh.
Pearson, R.C.A. (1995). Cerebral cortex. In Gray’s anatomy  (38th edn) 
(ed. P .L. Williams, L.H. Bannister, M.M. Berry, et al.), pp. 1141–71. 
Churchill Livingstone, Edinburgh.Passingham, R. (1993). The frontal lobes and voluntary action . Oxford 
Paxinos, G. (ed.) (1990). The human nervous system . Academic Press, 
San Diego, CA.
T ovée, M.J. (1996). An introduction to the visual system . Cambridge 
Zeki, S. (1993). A vision of the brain . Blackwell Science, Oxford.
2.3.2 Neurodevelopment
Neural induction

The central nervous system originates from the midline region of 
the embryo as a specialized area of ectoderm, the neuroectoderm, or neural plate. FGF (ﬁ  broblast growth factor) signalling and BMP 
(bone morphogenetic protein) as well as Wnt (wingless gene) inhi-bition are required as steps for neural induction.
(1) However, the 
complete set of factors and their respective interactions are pre-sently not sufﬁ  ciently understood in the mammalian embryo. As

complete set of factors and their respective interactions are pre-sently not sufﬁ  ciently understood in the mammalian embryo. As 
the neuroectodermal cells proliferate the neural plate is trans-formed into an indentation, the neural groove. The lateral parts of this groove approach each other and join in the midline, forming the neural tube. The folds begin to fuse in the central part of the groove but the most rostral and caudal parts close only later, leav-ing initially rostral and caudal neuropores. A small transitional zone between the neural plate and the surrounding ectoderm pro-vides the cells of the neural crest, which develop into the postgan-glionic cells of the sympathetic and parasympathetic nervous sys-tem, the sensory neurons of the spinal ganglia and ganglia of cranial nerves, Schwann cells, and chromafﬁ  ne cells of the supra-
renal glands.
Neural tube formation requires a controlled expression of cell

Neural tube formation requires a controlled expression of cell 
adhesion molecules in the lateral folds of the neural groove. If the rostral neuropore fails to close, the development of the forebrain is impaired leading to anencephaly. If the caudal neuropore fails to close, the most severe result is rachischisis, a malformation with a dorsally exposed neural groove. The mildest result is spina biﬁ  da 
occulta which is a cleft of a vertebral arch covered by epidermis.
As development continues, the neural tube and crest move to a 
position between the ectoderm and the notochord. The rostral part of the neural tube differentiates into the brain; the caudal part (behind the ﬁ  fth somite) differentiates into the spinal cord.
Organogenesis of the central nervous system
The embryonic brain has three vesicular enlargements: the forebrain,

The embryonic brain has three vesicular enlargements: the forebrain, 
telencephalon and diencephalon, the midbrain, mesencephalon, and the hindbrain, rhombencephalon. Because the brain grows much faster than the rest of the embryo, it becomes deﬂ  ected ven-
trally. A dorsally convex cephalic ﬂ  exure marks the border between 
hindbrain and midbrain, and a cervical ﬂ  exure marks the border 
between spinal cord and hindbrain (Fig. 2.3.2.1). The ventrally convex pontine ﬂ  exure forms the hindbrain. During week 5, the 
forebrain differentiates further into the rostral telencephalon and the more caudal diencephalon. The telencephalon consists of two

157
hemispheric vesicles connected by a thin lamina terminalis, the 
most dorsal part of which develops into the commissural plate, 
theAnlage  of the corpus callosum. The ventral part of the lamina 
terminalis differentiates into the anterior commissure. The central 
cavity of the diencephalon (the third ventricle) is connected with 
the cavities of the hemispheric vesicles (the lateral ventricles) by 
the interventricular foramen. The diencephalon develops bilateral 
evaginations, the eye vesicles, which differentiate into the retina 
and the optic nerve. Meanwhile the hindbrain becomes subdivided 
into a rostral metencephalon and a caudal myelencephalon.
The cerebellum starts to develop from the metencephalon dur-
ing week 6 (Fig. 2.3.2.1). At ﬁ  rst, the enlarged central cavity of the 
neural tube (the future fourth ventricle) has a thin roof plate 
bordered by two thickenings of the neural tube, the rhomboid lips, 
which merge in the midline. These thickenings develop into the

which merge in the midline. These thickenings develop into the 
cerebellar hemispheres, while the midline part develops into the 
vermis of the cerebellum. Fissures appear in the cerebellar hemi-
spheres, forming the anterior and posterior lobes and the uvula.
The rhombencephalon is temporarily divided into eight rhom-
bomeres,(2) whose borders are speciﬁ  ed by speciﬁ  c combinations 
of transcription factors (e.g. Hox, Krox, Wnt genes) disappear during
further development. Local expression of homeobox genes leads to 
the formation of the pallium and the ganglionic hill in the forebr ain.
The hindbrain develops in close association with the visceral 
archs, which appear during week 4. It innervates these archs and 
the organs derived from them by a group of branchial nerves, 
which later become the trigeminal (V), facial (VII), glossopharyn-

geal (IX), vagal (X), and accessory (XI) cranial nerves. Other cranial 
nerves develop connections between the hindbrain and peripheral 
organs not derived from the visceral archs. They are the oculomo-
tor (III), trochlear (IV), abducens (VI), vestibulocochlear (VIII), 
and hypoglossal (XII) nerves. The olfactory (I) and optic (II) nerves 
arise separately as evaginations of the forebrain.
Histogenesis of the spinal cord
The neural tube initially consists of a single layer of neuroepithelial 
cells surrounding a central canal ﬁ  lled with the cerebrospinal ﬂ  uid. 
The outer surface of the future spinal cord has an external limiting 
membrane, and the inner surface bordering the central canal has 
an inner limiting membrane. The entire wall of the early neural

an inner limiting membrane. The entire wall of the early neural 
tube is called the ventricular zone.(3)
The cells of the ventricular zone proliferate, and the surface of 
the spinal cord enlarges. The cord then thickens as cells divide fur-
ther to produce a multilayered epithelium. The daughter cells have 
different potentialities: one type of cell (the neuroblast) retains the 
capability for mitosis, whereas another type (the proneurone) is 
postmitotic and represents an immature neurone. The prolifera-
tion of neurones is almost complete around birth.
Some neuroepithelial cells develop into precursors of glial cells, 
glioblasts, which differentiate into astroglial, oligodendroglial, and 
microglial cells. The first glioblasts differentiate into radially 
extended cells spanning the entire width of the wall of the spinal

extended cells spanning the entire width of the wall of the spinal 
cord (the same occurs in the cerebral hemispheres and the cerebel-
lar cortex as described below). During later development these cells 
are transformed into ependymal cells and astroglia.
The histogenesis of the spinal cord starts at the cervical level and 
progresses in a caudal direction. After week 3, a longitudinal sulcus 
limitans is recognizable on the inner surface of the neural tube, dividing the wall into dorsal (alar) and ventral (basal) plates. The 
dorsal plates of both sides are connected by a thin roof plate, and 
the ventral plates by a thin ﬂ  oor plate. The dorsal plate differenti-
ates into a sensory zone, the dorsal horn of the adult spinal cord, 
and the ventral plate differentiates into a motor zone, the ventral 
horn. The sympathetic preganglionic neurones form the lateral

horn. The sympathetic preganglionic neurones form the lateral 
horn, which is present only at thoracic levels. The subdivision into 
dorsal and ventral plates is functionally important not only in the 
spinal cord, but also in the brainstem (see below).
During week 5, three concentrically organized zones—a cell-
dense ventricular zone, a less-dense intermediate or mantle zone, 
and a superﬁ  cially located marginal zone free of neuronal cells—
develop in the wall of the spinal cord. Proneurones leave the ven-
tricular zone and migrate along radial glial cells into the intermedi-
ate zone where they become organized into cell groups, nuclei. The 
motor neurones develop the axons of the ventral root, and the 
processes from spinal ganglionic cells grow into the spinal cord to Fig. 2.3.2.1 Development of the human brain. Brains of (a) 4 mm, (b) 10.4 mm

processes from spinal ganglionic cells grow into the spinal cord to Fig. 2.3.2.1 Development of the human brain. Brains of (a) 4 mm, (b) 10.4 mm 
(c), 13.8 mm, and (d) 53 mm human embryos, and (e) 21 week and (f ) 24 week 
fetuses. C, cerebellum or cerebellar Anlage ; CEF, cervical ﬂ  exure; CF, cephalic ﬂ  exure; 
CS, central sulcus; D, diencephalon; ES, eye stalk; EV, eye vesicle; FL, frontal lobe; 
H, hindbrain; HV, hemispheric vesicle; IL, insular lobe; LF, lateral ﬁ  ssure; LT, lamina 
terminalis; M, mesencephalon; MO, medulla oblongata; N.II, optic nerve; N.V, 
trigeminal nerve; N. VII, facial nerve; OL, occipital lobe; OLB, olfactory bulb; P , pons; 
PF, pontine ﬂ  exure; PL, parietal lobe; T, telencephalon; TE, tectum; TL, temporal 
lobe; IV.V, fourth ventricle.
2.3.2 neurodevelopment

SECTION 2  the scientific basis of psychiatric aetiology 158
form the dorsal roots. Synapses develop ﬁ  rst in the motor zone, and 
later in the sensory zone, during the weeks 10 to 13.
During the third month, the ventricular zone is reduced to a 
small rim surrounding the central canal and is ﬁ  nally transformed 
into the ependymal cell layer. The intermediate zone becomes organized into dorsal, ventral, and (at thoracic levels) lateral horns. The ascending and descending ﬁ  bre tracts of the spinal cord are 
increased in size in the marginal zone. During weeks 14 and 15, oligodendrocytes begin to myelinate these ﬁ  bre tracts. The corti-
cospinal, or pyramidal, tract is visible for the ﬁ  rst time during week 
14 and reaches its target neurones, mainly motor neurones of the ventral horn, between weeks 17 and 29. The myelination of the pyramidal tract is completed between the ﬁ  rst and second postna-

tal years. This late myelination explains the presence of the Babinski reﬂ ex in newborns and its disappearance during the ﬁ  rst 2 years.
Histogenesis of the brainstem and 
cerebellum
At the level of the fourth ventricle the various zones of the hind-
brain are arranged in a lateral-to-medial sequence (somatosenso-ry-viscerosensory-visceromotor-somatomotor). In the hindbrain, proneurones not only migrate radially, as in the spinal cord, but also tangentially and longitudinally. This complex migration and the growth of ﬁ  bre tracts lead to changes of the lateral-to-medial 
sequence of cranial nerve nuclei (e.g. the facial nucleus) in the adult.
In the cerebellum, between weeks 10 and 11, neuroblasts migrate

In the cerebellum, between weeks 10 and 11, neuroblasts migrate 
from the ventricular zone through the intermediate zone into an area (the external granular layer) at the surface of the marginal zone. During weeks 12 and 13, proneurones from the ventricular zone begin to migrate along radially extended glial cells, Bergmann glia, into a region below this external granular layer, where they 
form the Purkinje cells of the ganglionic layer of the cerebellar cor-
tex. Other proneurones from the ventricular zone develop into the cerebellar nuclei. Proneurones from the external granular layer then migrate inwards to form the internal granular layer and the basket and star cells of the molecular layer. The migration of cere-bellar proneurones is not completed until the ﬁ  rst postnatal year. 
During weeks 16 and 26, synapses develop and afferent ﬁ  bre sys-

tems begin to form. The external granular layer ﬁ  nally disappears 
during the ﬁ  rst 2 years of life, leaving the three-layered organiza-
tion (molecular, ganglionic, and internal granular layers) of the adult cerebellar cortex.
Histogenesis of the cerebral cortex
Initially, the entire wall of the hemispheric vesicle consists of very densely packed mitotic cells. These cells undergo more than 28 mitotic rounds in the human brain.
(4) In week 5, this develops into 
an inner cell-dense periventricular zone and an outer cell-poor marginal zone. In week 6, postmitotic proneurones leave the inner periventricular zone and form an intermediate (mantle) zone between the marginal and periventricular zones. By the end of week 6, the periventricular zone is further subdivided into a cell-dense ventricular zone and a less cell-dense subventricular zone.
During week 8, the cortical plate between the marginal and inter-

mediate zones is formed by proneurones which have migrated along radial glial cells from the ventricular and subventricular 
zones through the intermediate zone.
(3–7) A single radial glial cell 
can span the entire distance between the ventricular and pial sur-faces. As the proneurones ‘climb’ to the cortical plate along the processes of the radial glial cell, they produce a vertically oriented cortical cell column. This radially guided migration is responsible for the architectonic organization of cortical layers II–VI. It is a prototype of the cortical map of the adult brain.
(8) A further fea-
ture of cortical migration is the inside-to-outside layering, with the earliest proneurones being found in the deepest layers of the corti-cal plate and the latest in the most superﬁ  cial layers. Thus layers V

and VI of the adult cortex are generated before layer IV , and layer IV is generated before layers III and II. When cortical proneurones are migrating radially, their ‘stop signal’ is Reelin, produced by spe-cialized cells (Cajal–Retzius cells) in the marginal layer. In this way, Reelin organizes the inside-to-outside layering of the cortex.
(4) In 
addition to Reelin, the microtubule-associated protein (LIS1), Doublecortin (DCX), and the tumour-suppressor p73 are crucial for the normal migration of the proneurones. These radially migrat-ing cells develop into the glutamatergic projection neurones 
(pyramidal neurones) of the cortex. At the same time there is much tangential migration of cells born in the ganglionic eminence, migrating into the cortical Anlage , and developing into γ-aminobu-
tyric acid producing (GABAergic) cortical interneurones.
(4,9)
Regional differences in the development of the cortical plate sub-

(4,9)
divide the hemisphere into segments. The lateral segment, with a well-developed cortical plate and presubplate, develops into the neocortex. The mediodorsal segment, with a wide marginal zone and a thin-folded cortical plate, develops into the archicortex, including the hippocampus. The mediobasal segment, with its inconspiciously developed cortical plate, is the precursor of the palaeocortex. The basolateral segment, ganglionic eminence, gen-erates cortical interneurones (see above) and develops into the cor-pus striatum, the amygdala, and the septum.
During weeks 10 and 12, the axons of the serotoninergic and 
noradrenergic neurones contribute to the ﬁ  rst synapses in the 
marginal and presubplate zones, where neurotrophin receptors (see below) are expressed. During the following 3 weeks, the sub-

plate zone develops as axons grow in from the basal forebrain 
and thalamus, dendrites enlarge, and synapses form. From weeks 16 to 24, the cortical Anlage  has a small marginal zone, a wide cell-
dense cortical plate, and a very wide and less cell-dense  subplate.
The transformation into the adult neocortical pattern starts 
between weeks 25 and 34 as the migration and proliferation of proneurones diminishes. Dendrites begin to differentiate and syn-apses begin to develop in the deepest cortical layers, progressing to the most superﬁ  cial layer. Before birth, six cortical layers can be 
recognized in all regions of the neocortex. In the postnatal period, layer IV (inner granular layer) disappears as part of the differentia-tion of the motor cortex, leaving the ﬁ  ve-layered agranular neocor-

tex of the motor region.
(10) Shortly before birth, the subplate, the 
subventricular zone, and most of the ventricular zone disappear, 
neuronal proliferation ceases, and the intermediate zone is trans-formed into the white matter of the pallium. The remaining ven-tricular zone contributes to the ependymal layer of the ventricular surface.
Dendritic and axonal differentiation continues after birth and 
into adult life. Synaptogenesis reaches a maximum during the ﬁ  rst

159
postnatal year, but continues at a lower rate during childhood. The 
myelination of the vestibular system is ﬁ  nished shortly before birth, 
that of the somatosensory, visual, auditory, pyramidal, and extrapy-
ramidal ﬁ  bre tracts is nearly complete by the end of the third post-
natal year, and that of the associative ﬁ  bre tracts in the cerebral 
hemispheres is continued until the second decade.(11) The key 
change in synapses after birth is pruning; the density of synapses in 
the adult brain is half that in neonates.
The development of the neocortex is summarized in Fig. 2.3.2.2.
Hemispheric shape and the formation 
of gyri
The spherical shape of the early foetal hemisphere is transformed 
into the adult shape by differing rates of growth in the various 
regions of the telencephalon (Fig. 2.3.2.1). The future insular lobe 
grows less than other telencephalic regions, so that by the eighth 
month it is covered by the frontal, parietal, and temporal lobes. In

month it is covered by the frontal, parietal, and temporal lobes. In 
the adult brain the insula is completely buried in the depth of the 
lateral ﬁ  ssure.
The extensive growth of the parieto-occipito-temporal associa-
tion cortex leads to a bend in the temporal lobe around the lateral 
ﬁ ssure. At the same time the temporal pole is pushed rostrally. 
This direction of growth (Fig. 2.3.2.1(d)) also affects the struc-
tures situated dorsomedially, i.e. the archicortex with the hippoc-
ampus, the corpus striatum, and the lateral ventricles. The corpus 
striatum is split by the ingrowing ﬁ  bres of the internal capsule 
into the caudate nucleus and the putamen. The head of the cau-date is situated ventrolaterally to the corpus callosum in the fron-
tal lobe, and the tail of the caudate is located in the temporal lobe 
dorsal to the inferior horn of the lateral ventricle. The hippocam-

pus forms its largest extension (the retrocommisssural part) 
in the temporal lobe, bends around the posterior end (splenium) 
of the corpus callosum, and reaches a position on top of the cor-
pus callosum (the supracommissural part). The precommissural 
part of the hippocampus ends in front of the genu of the corpus 
callosum.
After the appearance of the lateral ﬁ  ssure, the neocortical surface 
develops many sulci and gyri. The central, collateral, cingulate, 
parieto-occipital, superior temporal, and calcarine sulci appear 
between weeks 16 and 21, followed by the pre- and postcentral, 
frontal, temporal, and intraparietal sulci. Highly variable secondary 
and tertiary sulci develop between week 29 and birth, when all sulci 
have been formed.(12,13)
The reasons for the formation of gyri in many mammalian

The reasons for the formation of gyri in many mammalian 
brains, including the human brain, are not completely understood. 
Since the basic organization of the cerebral cortex is vertically ori-
ented, with cell columns positioned side by side, growth of the cor-
tex inevitably leads to a considerable enlargement of the cortical 
surface. A large unfolded cortical surface would have two disadvan-
tages: the volume of the skull would increase to such a degree dur-
ing foetal development that a normal delivery would be impossible; 
the distance between cortical regions interconnected by intrahemi-
spheric projection ﬁ  bres would increase and with it the informa-
tion transmission time. Gyri allow the maximal cortical surface in 
the minimal volume, and they increase the speed of neural trans-
mission between neighbouring cortical areas. Recent measure-

ments show that gyriﬁ  cation is greatest in the association cortices. 
Although all gyri and sulci are present at birth, the depth of the 
sulci increases until two-thirds of the cortical surface is hidden in 
them.(12)
Genetic factors during development
The co-ordinated expression, in space and time, of many genes 
underlies neurodevelopment. Mutations in these ‘neurodevelop-
mental genes’ are increasingly being recognized as causes of 
developmental neurological disorders such as cortical dysplasia 
and epilepsy; they may also be relevant to learning disability and 
schizophrenia. Different gene families are involved in the major 
component processes of neurodevelopment, such as organogenesis, 
neurogenesis, neuronal migration, synaptogenesis, and program-

med cell death (apoptosis).(14, 15) The details are beyond the scope 
of this book, but a few examples are given here.
Neurotrophins (growth factors) are genes which, as their name 
suggests, are critical for neuronal growth and survival, especially 
via their inﬂ  uence on apoptosis which is promoted by insufﬁ  ency 
of neurotrophins such as nerve growth factor and inhibited by 
enhanced nerve growth factor functioning. The effects of neuro-
trophins are mediated by speciﬁ  c tyrosine kinase (Trk) receptors 
(Table 2.3.2.1). Classical neurotransmitters and their receptors are 
also involved in neurodevelopment, both directly in the formation 
of synaptic connections and indirectly through regulation of neu-
rotrophins and Trk receptors; particular roles have been shown

rotrophins and Trk receptors; particular roles have been shown 
for glutamate, acting via N-methyl- d-aspartate receptors, as well as 
forγ-aminobutyric acid (GABA) and acetylcholine.Fig. 2.3.2.2 Development of the neocortex between 4 weeks of gestation 
and adulthood. Roman numerals indicate the six cytoarchitectonically deﬁ  ned 
layers of the neocortex, which originate from the marginal zone (layer I) and the 
cortical plate. CP , cortical plate; IZ, intermediate zone; MZ, marginal zone; SP , 
subplate; SVZ, subventricular zone; VZ, ventricular zone; WM, white matter.

SECTION 2  the scientific basis of psychiatric aetiology 160
Rao, M.S. and Jacobson, M. (eds.) (2005). Developmental neurobiology .
Sanes, D.H., Reh, T.H. and Harris, W.A. (2006). Development of the nervous 
system  (2nd edn). Academic Press, Amsterdam.
Squire, L.R., Bloom, F.E., McConnell, S.K., et al.  (eds.) (2005). Fundamental 
neuroscience  (2nd edn), chapters 14–21. Academic Press, 
Amsterdam.
 1. Ladher, R. and Schoenwolf, G.C. (2005). Making a neural tube: 
neural induction and neurulation. In Developmental neurobiology
(eds. M.S. Rao and M. Jacobson), pp. 1–20. Kluwer Academic/Plenum Publishers, New Y ork.
 2. Lumsden, A. and Krumlauf, R. (1996). Patterning the vertebrate 
neuraxis. Science ,274, 1109–15.
 3. Kostovic, I. (1990). Zentralnervensystem. In Humanembryologie
(ed. K.V . Hinrichsen), pp. 381–448. Springer-Verlag, Berlin.
 4. Meyer, G. (2007). Genetic control of neuronal migrations in human

3. Kostovic, I. (1990). Zentralnervensystem. In Humanembryologie
 4. Meyer, G. (2007). Genetic control of neuronal migrations in human 
cortical development. Advances in Anatomy Embryology and Cell 
Biology ,189, 1–114.
 5. Levitt, P . and Rakic, P . (1980). Immunoperoxidase localization of glial 
ﬁ brillary acid protein in radial glial cells and astrocytes of the developing 
rhesus monkey brain. Journal of Comparative Neurology ,193, 815–40.
 6. Rakic, P . (1985). Limits of neurogenesis in primates. Science ,227,
154–6.
 7. Supèr, H., Soriano, E., and Uylings, H.B.M. (1998). The functions of 
the preplate in development and evolution of the neocortex and hippocampus. Brain Research Reviews ,26, 40–64.
 8. Rakic, P . (1988). Speciﬁ  cation of cerebral cortical areas. Science ,241,
170–6.
 9. Rakic, P . (1995). Radial versus tangential migration of neuronal clones

8. Rakic, P . (1988). Speciﬁ  cation of cerebral cortical areas. Science ,241,
170–6.
 9. Rakic, P . (1995). Radial versus tangential migration of neuronal clones 
in the developing cerebral cortex. Proceedings of the National Academy 
of Sciences of the United States of America ,92, 11323–7.
10. Brodmann, K. (1909). Vergleichende Lokalisationslehre der Großhirnrinde 
in ihren Prinzipien dargestellt auf Grund des Zellenbaues . Barth, 
Leipzig.
11. Y akovlev, P .I. and Lecours, A.-R. (1967). The myelogenetic cycles of 
regional maturation of the brain. In Regional development of the brain in early life  (ed. A. Minkowski), pp. 3–70. Blackwell Science, 
Oxford.
12. Zilles, K., Armstrong, E., Schleicher, A., et al.  (1988). The human 
pattern of gyriﬁ  cation in the cerebral cortex. Anatomy and Embryology ,
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13. Armstrong, E., Zilles, K., Omran, H., et al.  (1995). The ontogeny of 
human gyriﬁ  cation. Cerebral Cortex ,5, 56–63.

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speciﬁ  cation of the cerebral cortex. Annual Review of Neuroscience ,
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15. Lambert de Rouvroit, C. and Gofﬁ  net, A.M. (1998). A new view of 
early cortical development. Biochemical Pharmacology ,56,
1403–9.
2.3.3 Neuroendocrinology
Deﬁ nitions and principles
In the late 1950s, a controversy arose in endocrinology and neuro-
science concerning whether neurones are capable of manufactur-ing and secreting hormones; that is to say, is it possible that certain neurones subserve endocrine functions? Much of the ensuing debate, which persisted for approximately two decades, was centred on two major ﬁ  ndings. First, led by a husband and wife team, the

Scharrers, a number of neurohistologists working with mammalian as well as with lower vertebrate and invertebrate species documented the presence—by both light and electron microscopy—of neurones that had all the characteristics of previously studied endocrine cells. They stained positive with the Gomori stain, which is claimed to be speciﬁ  c to endocrine tissues, and they incorporated granules 
or vesicles containing the endocrine substance purportedly released by these cells. The second major avenue of investigation centred 
around the brain’s control of the secretion of the pituitary trophic

around the brain’s control of the secretion of the pituitary trophic 
hormones, which in turn were long known to control the secretion of the peripheral target endocrine hormones such as thyroid hor-mones, gonadal steroids, adrenal steroids, etc. A critical observation by several investigators had earlier demonstrated the existence of a vital neuroendocrine system, namely the magnocellular cells of the paraventricular nucleus of the hypothalamus that synthesized vasopressin and oxytocin, the nonapeptides that are transported down the axon to the nerve terminals of these neurones in the pos-terior pituitary (neurohypophysis) and released in response to physiological stimuli. For example, the release of vasopressin, or the antidiuretic hormone, as it is commonly named, acts as a criti-cal regulator of ﬂ  uid balance, and oxytocin is known to regulate 
the milk-letdown reﬂ  ex during breast feeding.
It is now ﬁ  rmly established that neurones are indeed capable of

It is now ﬁ  rmly established that neurones are indeed capable of 
functioning as true endocrine tissues, synthesizing and releasing substances, known as (neuro)hormones, which are released directly into the circulatory system and transported to distant sites of action. The release of vasopressin from the posterior pituitary gland and its action on the kidney is one often cited example; the action of the hypothalamic release and release-inhibiting factors on the anterior pituitary trophic hormone-producing cells is another.Table 2.3.2.1  Important neurotrophins, their sites of synthesis in 
the central nervous system, receptors, and target structures
Neurotrophin Site of synthesis Receptors Target structures
NGF Hippocampus 
NeocortexTrkA, p76NTR Cholinergic neurones in 
the basal forebrain
BDNF Hippocampus 
NeocortexTrkB. p75NTR Dopaminergic neurones 
in the midbrain; 
retinal ganglionic cells;

retinal ganglionic cells; 
cholinergic neurones in the basal forebrain
NT-3 Hippocampus 
CerebellumTrkC, p75
NTRDopaminergic neurones 
neurones of the nucleus 
mesencephalicus nervi trigemini; neurones of 
origin of the pyramidal 
tract
NGF, nerve growth factor; BDNF, brain-derived neurotrophic factor; NT-3, neurotrophin 3.

161
Pleiotropic roles—endocrine factors and 
neurotransmitters
Although, it was clearly important to document the ability of 
neurones to function as neuroendocrine cells, particularly those in the central nervous system (CNS), the focus on an artiﬁ  cial classiﬁ  -
cation system with clear demarcations of endocrine versus neuro-nal versus neuroendocrine, quickly lost its heuristic value. Indeed, we now recognize that the very same substance, often function at one site as an endocrine substance and at another as a neurotrans-mitter. Thus, adrenaline (epinephrine) functions as a hormone in the adrenal medulla and as a conventional neurotransmitter sub-stance in the mammalian CNS. Similarly corticotrophin-releasing factor (CRF) functions as a true hormone in its role as a hypotha-lamic hypophysiotrophic factor in the hypothalamic anterior pituitary complex, yet it is apparently a ‘conventional’ neurotrans-mitter in cortical and limbic brain areas. It may act as a paracrine

substance in the adrenal medulla (see Fig. 2.3.3.1). Thus, the ﬁ  eld 
has progressed to the stage where we now strive to characterize the role of a particular chemical messenger in a particular region or endocrine axis. The traditional endocrine and neurotransmitter roles for several peptides alluded to above are ﬁ  rmly established, 
but the equally important paracrine roles for such substances, namely the secretion of a substance from one cell where it acts upon nearby cells, remain largely unexplored. This is, perhaps, best illustrated in the gastrointestinal tract where several peptides that function as hormones or neurotransmitter substances in other sites, including the CNS, act to inﬂ  uence local cellular function. 
Examples would include vasoactive intestinal peptide, cholecysto-kinin, and somatostatin.
Neuroendocrinology

Neuroendocrinology thus, comprises the study of the endocrine role of neuronal or glial cells as well as the neural regulation of endocrine secretion, with a major portion of the latter consisting of the biology of the various hypothalamic-pituitary-end-organ axes and the major neurohypophyseal hormones, vasopressin and oxytocin. Because of the elegant and precise regulation of periph-eral endocrine hormone secretion, afforded in part by the feedback of peripherally secreted hormones at pituitary and a variety of CNS sites, the actions of such hormones on the brain has become an integral part of this discipline. The related discipline of psycho-
neuroendocrinology  arose with the realization that there are bind-

ing sites (receptors) for peripheral hormones within the CNS that have little to do with the feedback regulation of the hypothalamic-pituitary-end-organ axes, and the further recognition of the semi-
nal role of the CNS in regulating endocrine function, for example 
in the effect of stress on several such measures. Often cited as begin-

ning with the pioneering observations of Berthold, who reported that removing roosters’ testosterone-secreting gonads abolished their sexual behaviour, psychoneuroendocrinology has been expanded to include the effects of hormones on behaviour, as well as the study of endocrine alterations in psychiatric disorders and, the converse, psychiatric symptomatology in endocrine disorders. Indeed, this stepchild of neuroendocrinology and psychosomatic medicine has been one of the most rapidly growing areas of research in psychiatry, now boasting an international society (International Society of Psychoneuroendocrinology), an annual meeting, and its own journal (Psychoneuroendocrinology).Neuroendocrine window

One of the most commonly used strategies in the 1970s and 1980s, still in occasional use today, is the so-called neuroendocrine ‘window’ strategy. Until the relatively recent development and availability of functional brain-imaging techniques, the brain remained relatively inaccessible for study, with the exception of cerebrospinal ﬂ  uid (CSF) and postmortem tissue studies. With the 
emergence of the monoamine theories of mood disorders and schizophrenia, many investigators attempted to draw conclusions about the activity of noradrenergic, serotonergic, and dopaminergic circuits in patients with various psychiatric disorders by measuring the basal and stimulated secretion of pituitary and end-organ hormones in plasma. There is little doubt that such an approach has severe limitations, but the results, now coupled with more modern approaches, have contributed to the substantial progress 
made in elucidating the pathophysiology of mood and anxiety

made in elucidating the pathophysiology of mood and anxiety 
disorders and, to a considerably lesser extent, schizophrenia. One assumption of the neuroendocrine window strategy is that the monoamine-containing neurones that regulate endocrine secre-tion are disordered (or not disordered) to the same extent as those monoamine circuits posited to be involved in the pathophysiology of the disorder under study. Such an assumption may well be true in neural circuits in which the cells of origin are found in a circum-scribed area and project to widely diffused areas of the CNS (for example, the serotonergic and noradrenergic projections to the forebrain from the raphe and locus coeruleus cells in the brainstem, 
respectively). In contrast are the various dopaminergic circuits in the CNS, with their well-known topographic point-to-point Fig. 2.3.3.1 Hormones of the hypothalamic-pituitary-end-organ axes: CRF,

respectively). In contrast are the various dopaminergic circuits in the CNS, with their well-known topographic point-to-point Fig. 2.3.3.1 Hormones of the hypothalamic-pituitary-end-organ axes: CRF, 
corticotrophin-releasing factor; TRH, thyrotrophin-releasing hormone; TSH, thyroid-stimulating hormone; T
3, tri-iodothyronine; T4, thyroxine; PRL, prolactin; 
GHRH, growth-hormone releasing hormone; GH, growth hormone; LH, luteinizing hormone; FSH, follicle-stimulating hormone.Hypothalamic
hypophysiotropic
factorAnterior
pituitary
harmone
CRF
(41 amino acids)
Somatostatin
(14 amino acids)inhibitsstimulatesinhibitsacts onstimulatesstimulates stimulates
Somatomedin C
Insulin-likegrowth
factor(16F-1)
Oestradiol
TestosteroneInhibinMammary glandCortisol
stimulatesT
3 and T4
stimulates
stimulatesLH, FSHPRLACTH
TSH
GHstimulates
stimulatesDopamine
Gonadotrophin-
releasing
hormone
(10 amino acids)GHRH
(44 amino acids)TRH
(3 amino acids)Endocrine
target
hormone2.3.3 neuroendocrinology

SECTION 2  the scientific basis of psychiatric aetiology 162
distribution. Thus, there is little reason to believe that the activity 
of the major dopamine-containing hypothalamic projection, the 
tuberoinfundibular system, with perikarya in the arcuate and peri-ventricular hypothalamic nuclei and projections to the median eminence, is in any way related to the activity of the mes-olimbicocortical dopamine pathway, with cell bodies in the ventral tegmentum of the midbrain and projections to the nucleus accumbens, amygdala, and cortical regions. This latter pathway has been implicated in the pathophysiology of schizophrenia. Thus, the study of the dopamine modulation of prolactin secre-tion in schizophrenia is unlikely to inform about the nature of limbic and cortical dopamine neuronal alterations in this devas-tating disorder.
Hypothalamic-pituitary-end-organ axes

Because a large portion of neuroendocrinology relevant to psychi-atry is concerned with the hypothalamic-pituitary-end-organ axes, alterations in each of these systems in patients with a major psychi-atric disorder are described later in this chapter. T o avoid repeti-tion, a generic description of the hierarchical organization of the various components of these systems is brieﬂ  y outlined here. More 
comprehensive reviews of this subject are available.
(1) In general,

(1) In general, 
the hypothalamus contains neurones that synthesize release and release-inhibiting factors. These peptide hormones, summarized in Fig. 2.3.3.1, are synthesized by a process beginning with transcrip-tion of the DNA sequence for the peptide prohormone. After trans-lation in the endoplasmic reticulum and processing during axonal transport and packaging in the vesicles in the nerve terminals, the now biologically active peptide is released from nerve terminals in the median eminence and secreted into the primary plexus of the hypothalamohypophyseal portal vessels. They are transported 
humorally to the sinusoids of the adenohypophysis where they act on speciﬁ  c membrane receptors on their speciﬁ  c target: the pitui-

tary trophic hormone-producing cells. Activation of their receptors results in the release or inhibition of release of the pituitary trophic hormone. The increase or decrease in pituitary trophic hormone secretion produces a corresponding increase or decrease in end-organ hormone secretion. Thus gonadotrophin-releasing 
hormone  (GnRH ), a decapeptide, induces the release of the 
gona dotrophins, luteinizing hormone, and follicle-stimulating hormone from the anterior pituitary gland, which in turn stimu-late the secretion of oestrogen and progesterone in women, and testosterone in men. The exogenous, intravenous administration of GnRH, comprises the GnRH stimulation test, a very sensitive test of hypothalamic-pituitary-gonadal ( HPG ) axis activity. Such stim-
ulation tests are thought to be a sensitive measure of the activity of

ulation tests are thought to be a sensitive measure of the activity of 
the axis because it is inﬂ  uenced by GnRH secretion, gonadotrophin 
secretion, and feedback at the pituitary and brain by gonadal steroids. The organization of, and major feedback mechanisms thus far demonstrated in the hypothalamic–anterior pituitary–end-organ axes are illustrated in Fig. 2.3.3.2.
In summary, neuroendocrinology (and the related discipline 
psychoneuroendocrinology) broadly encompasses the study of the following:
◆ the neural regulation of peripheral, target-organ hormone 
secretions, pituitary trophic hormone secretions, and secretions of the hypothalamic-hypophysiotrophic hormones;
◆ the role of neurotransmitter systems in the regulation of the 
above;
Fig. 2.3.3.2 Relationships between 
brain neurotransmitter systems, hypothalamic peptidergic (releasing-factor) neurones, anterior pituitary, and peripheral endocrine organs, 
illustrating established feedback loops:

illustrating established feedback loops: 
LHRH, luteinizing-hormone releasing hormone; SRIF, somatostatin; MIF, melanotrophin release-inhibiting factor; GHRF, growth-hormone releasing factor. Other abbreviations as in Fig. 2.3.3.1.

163
◆ the hormone effects of each of the endocrine axes on the CNS, 
alterations in the activity of the various endocrine axes in major psychiatric disorders, and conversely the behavioural conse-quences of endocrinopathies;
◆ the effects of target gland hormones on the CNS in normal 
individuals—for instance, the effects of synthetic glucocorticoids on memory processes.
The hypothalamic-pituitary-thyroid axis
It has been recognized for more than a century that adult patients with hypothyroidism exhibit profound disturbances in CNS func-tion, including cognitive impairment and depression. In more recent years, attention has focused on more subtle alterations of the hypothalamic-pituitary-thyroid ( HPT ) axis in depressed patients. 
Hypothyroidism  is most frequently subclassiﬁ  ed as in four grades 
◆ Grade 1 hypothyroidism is classic primary hypothyroidism 
(increased thyroid-stimulating hormone  (TSH ), decreased

(increased thyroid-stimulating hormone  (TSH ), decreased 
peripheral thyroid hormone concentrations, and an increased TSH response to thyrotrophin-releasing hormone  (TRH )).
◆ Grade 2 hypothyroidism is characterized by normal, basal 
thyroid-hormone concentrations, but an increase in basal TSH concentrations and an exaggerated TSH response to TRH.
◆ Grade 3 hypothyroidism can only be detected by a TRH-
stimulation test; patients have a normal basal thyroid hormone 
and TSH concentrations, but an exaggerated TSH response to TRH.
◆ Grade 4 hypothyroidism is deﬁ  ned as normal ﬁ  ndings on the 
three thyroid axis function tests noted above, but the patients have antithyroid antibodies.
Left untreated, most, if not all, patients’ progress from grade 4 to

Left untreated, most, if not all, patients’ progress from grade 4 to 
grade 1 hypothyroidism. Several studies have revealed an inordi-nately high rate of HPT axis dysfunction, largely hypothyroidism, in patients with major depression. In our pilot study, patients with comorbid depression and anxiety were especially likely to exhibit HPT axis abnormalities, especially the presence of grade 4 hypo-thyroidism, i.e. symptomless autoimmune thyroiditis. Patients with other major psychiatric diagnoses including schizophrenia and anxiety disorders appear to exhibit normal HPT axis function. For patients who require thyroid hormone replacement secondary to thyroid ablation, Bunevicius et al .
(2) recently reported that treat-
ment with a combination of tri-iodothyronine  (T3) and thyrox-
ine (T4) is optimal for mood and cognitive function, rather than 
the standard medication of T4 alone.

In addition, a blunted TSH response to TRH is observed in 
approximately 25 per cent of patients with major depression. This observation, ﬁ  rst reported by Prange et al .
(3) and Kastin et al .,(4)
more than 25 years ago, has been replicated in many studies. 
Unfortunately, the pathophysiological underpinnings of this obser-vation remain obscure, though there is considerable evidence that it may be due, at least in part, to chronic hypersecretion of TRH and subsequent TRH-receptor downregulation in the anterior pituitary gland. Indeed, our group
(5) and others have reported elevated TRH 
concentrations in the CSF of drug-free depressed patients.
TRH was the first of the hypothalamic-releasing factors to

TRH was the first of the hypothalamic-releasing factors to 
be chemically characterized. Immunohistochemical and radio-immunoassay methods revealed a heterogeneous brain dis-
tribution of TRH. This was the ﬁ  rst in a series of experimental 
results that led to the inexorable conclusion that this peptide, and, as discussed below, other release and release-inhibiting hormones, function in extrahypothalamic brain regions as neurotransmitter substances. Thus, TRH has been shown to produce direct brain effects, independent of its action on the pituitary thyrotrophs. Antidepressant effects of intravenously and intrathecally applied TRH have been reported,
(3) but the results have not been conﬁ  rmed 
in large, controlled clinical trials.(6) In contrast, several reports over 
the last 30 years have documented the efﬁ  cacy of T3 (25–50 mg

the last 30 years have documented the efﬁ  cacy of T3 (25–50 mg 
daily) in both accelerating the rate of onset of antidepressant response,
(7) and in converting antidepressant non responders to 
responders,(8) the later conﬁ  rmed in the recent NIMH-funded 
STAR-D trial.(9) Studies also suggest that T4 (100–300 μg daily) 
supplementation is a viable strategy for increasing the response to antidepressants.
(10) These studies were initiated when it became

(10) These studies were initiated when it became 
apparent that patients (and laboratory animals) with hypothyroid-ism do not respond to antidepressant agents. This led to the hypothesis that patients with subtle forms of hypothyroidism (grades 2–4) may not respond optimally to antidepressants unless they are adequately treated with exogenous thyroid hormone. With the cloning of the thyroid hormone receptor and its localization within the CNS, studies of its regulation in depression, as well as the regulation of TRH biosynthesis, can now be conducted in postmortem brain tissue.
The hypothalamic-pituitary-adrenal axis
Although, ﬁ  rst identiﬁ  ed in crude form in 1955 by Saffran et al.,(11)
corticotrophin-releasing factor  (CRF ) was not chemically 
identiﬁ  ed until 1981 by Vale and colleagues.(12) This discovery 
ﬁ nally permitted the comprehensive assessment of hypothalamic-

pituitary-adrenal ( HPA ) axis activity, and also led to scrutiny of 
the role of this peptide, which is now known to co-ordinate the endocrine, immune, autonomic, and behavioural effects of stress in a variety of psychiatric disorders.
CRF hypothesis of depression
Most investigators would agree that the most important ﬁ  nding 
in all of biological psychiatry is the hyperactivity of the HPA axis observed in a signiﬁ  cant subgroup of patients with major depression. 
The magnitude of HPA axis hyperactivity has been reported to be correlated to the severity of the depression.
(13) Literally thousands

(13) Literally thousands 
of reports on this subject have appeared since the original and independent observations of research groups led by Board, Bunney, and Hamburg, as well as by Carroll, Sachar, Stokes, and Besser. These studies, conducted from the late 1950s to the 1980s, applied the tests largely developed for the diagnosis of Cushing’s syndrome to patients with major depression and other psychiatric disorders. A panoply of such tests, ranging from urinary free-cortisol, to CSF levels of cortisol, to the dexamethasone suppression test led to the inexorable conclusion that a sizeable percentage of depressed patients exhibited HPA axis hyperactivity. Our group and others, focusing on the mechanism(s) responsible for these ﬁ  ndings, 
documented adrenocortical enlargement
(14) and pituitary gland 
enlargement(15) in depressed patients, using CT and magnetic

enlargement(15) in depressed patients, using CT and magnetic 
resonance imaging ( MRI ) respectively. The hypersecretion of cor-
tisol is associated with hypersecretion of ACTH (and its co-secreted 2.3.3 neuroendocrinology

SECTION 2  the scientific basis of psychiatric aetiology 164
product of the precursor pro-opiomelanocortin), which due to its 
trophic properties also causes adrenocortical gland enlargement. 
Both direct measurements of CRF in CSF,(16) and of CRF and gene 
expression for CRF (CRF mRNA expression) in postmortem tissue conﬁ  rmed the hypothesized hypersecretion of CRF in depressed 
patients.
(17) In addition, CRF hypersecretion results in CRF1 recep-
tor downregulation observed in both receptor binding studies(18)
and CRF mRNA expression studies conducted on post-mortem tissue from suicide victims.
(19) Like the hypersecretion of cortisol, 
CRF hypersecretion normalizes upon recovery from depression. Indeed, there is now considerable evidence, derived from both preclinical and clinical studies, that CRF neuronal hyperactivity is reduced by treatment with several antidepressants including paroxetine and ﬂ  uoxetine, the selective serotonin-reuptake inhibi-

tors ( SSRIs ), reboxetine (the noradrenaline-reuptake inhibitor), 
venlafaxine (the dual noradrenaline/serotonin-reuptake inhibitor), desipramine (the tricyclic antidepressant), and tranylcypromine (the monoamine oxidase inhibitor), as well as by electroconvulsive therapy.
(20)
When patients who are drug free but depressed are given CRF

(20)
When patients who are drug free but depressed are given CRF 
intravenously, they exhibit, as a group, a blunted ACTH response compared with normal control subjects. This is believed to be secondary to either the downregulation of CRF receptors on the corticotrophs after long-standing CRF hypersecretion and/or intact negative feedback of the hypersecreted cortisol at anterior pituitary and higher CNS centres. As with the other measures of HPA axis function, this endocrine abnormality normalizes upon recovery from depression. Indeed, persistent alterations in HPA axis func-tion, whether due to dexamethasone non-suppression or CSF-CRF hypersecretion, is the harbinger of a poor response to antidepres-sant treatment. In recent years, Holsboer et al.
(21) have pioneered 
the use of the combined dexamethasone-CRF test , in which

the use of the combined dexamethasone-CRF test , in which 
patients are given the synthetic glucocorticoid and the following day receive a standardized CRF stimulation test. The results reveal that this test has a much greater sensitivity in detecting increases in HPA axis activity; it has now been used to detect axis alterations in the ﬁ  rst-degree relatives of depressed patients who have never 
been symptomatic, raising for the ﬁ  rst time the question of a trait 
(vulnerability) component to this measure.
(22)
Space constraints preclude a more comprehensive discussion of

(22)
Space constraints preclude a more comprehensive discussion of 
this rich literature, but a few additional points are certainly worth interjecting. First, a robust preclinical literature has documented the depressogenic and anxiogenic effects of exogenously adminis-tered CRF in laboratory animals. When CRF was directly injected into the central nervous system it produced effects reminiscent of the cardinal symptoms of depression in patients, including decreased libido, reduced appetite and weight loss, sleep distur-bances, and neophobia. Indeed, newly developed CRF1-receptor antagonists represent a novel putative class of antidepressants. Such compounds exhibit activity in virtually every preclinical screen for 
antidepressants and anxiolytics currently employed, and in an 
open study a CRF1 receptor antagonist was shown to possess anti-depressant properties.

(23) A second CRF receptor, the CRF2 receptor, 
exhibits genetic polymorphism (i.e. it occurs in more than one naturally occurring isoform or splice variant), and it is believed to utilize the urocortins as endogenous ligands. The long-term conse-quences of cortisol hypersecretion in depression are just now being scrutinized. One such sequela appears to be neuronal loss in the hippocampus, one of the major feedback sites for glucocorticoids 
in the CNS. This has now been documented by structural brain-imaging studies that utilized MRI techniques.
(24) If the degenera-

tion of neurones that represent glucocorticoid feedback sites indeed occur in depressed patients, then this should further increase HPA axis hyperactivity, which would explain the many reports of increas-ing adrenocortical hyperactivity of elderly depressed patients when compared with matched younger depressed patients.
Future studies will focus on the development of positron emis-
sion tomography ( PET ) ligands for both the glucocorticoid recep-
tor and the CRF receptor, the role of the CRF binding protein—a unique protein which binds CRF in extracellular ﬂ  uid and in plas-

ma, preventing its availability to act on its receptor—and the role of the CRF peptidase, which degrades the peptide, in normal and pathological states. Finally, are the studies from our group and others, which have documented the long-term persistent increases in the HPA axis and extrahypothalamic CRF neuronal activity after exposure to early untoward life events—for example, child abuse and neglect in both laboratory animals (rats and non-human primates) as well as in both male and female patients.
(20,25,26) This 
phenomenon has been posited to underlie the now well-documented association between early abuse and neglect and increased vulner-ability to mood disorders.
(27–29) Indeed, we have recently demon-

strated single nucleotide polymorphisms (SNPs) of the CRF1 receptor that confer vulnerability or resistance to the development of depression after exposure to child abuse.
(30) An early interven-
tion strategy using CRF receptor antagonists may prevent such long-term alterations in the central nervous system.
HPA axis and other psychiatric disorders

HPA axis alterations have also been investigated in other psychiatric disorders. When depression is comorbid with a variety of other dis-orders such as multiple sclerosis, Alzheimer’s disease, multi-infarct dementia, Huntington’s disease, and others, both CRF hypersecre-tion and HPA axis hyperactivity are common. There is little evi-dence for HPA axis dysfunction in schizophrenia. In contrast, at least one anxiety disorder, post-traumatic stress disorder, is associ-ated with extrahypothalamic CRF hypersecretion, as evidenced by elevated CSF concentrations of CRF,
(31) but normal or reduced 
measures of adrenocortical activity. Finally, CRF neuronal degen-eration is now well known to occur in the cerebral cortex of patients with Alzheimer’s disease,
(32, 33)  an effect which temporally occurs

(32, 33)  an effect which temporally occurs 
prior to the better-studied cholinergic neuronal involvement. With the reduction in CRF concentrations in the cerebral cortex there is a reciprocal increase in CRF receptor density. Whether modiﬁ  cation of the disease-associated effects on the CRF neuronal 
system in the cortex and hippocampus represents a novel strategy for the treatment of this common dementing disorder remains unclear at the present time.
The hypothalamic-growth hormone axis
Although the HPA and HPT axes have been more closely scrutinized in patients with psychiatric disorders, there is virtually universal agreement that the blunted growth-hormone response to a variety of provocative stimuli (particularly clonidine, an α2-adrenergic 
agonist) in depressed patients is the most consistent ﬁ  nding in 
affective disorders research.
(34) The mechanism underlying this

165
phenomenon remains obscure, but it is of particular interest that, 
at least in some studies, it appears to persist upon recovery from 
depression, suggesting that it is a trait marker for depression vulnerability. There are reports of similar ﬁ  ndings with other 
growth hormone-provocative stimuli, such as the use of apomor-
phine, desipramine, or levodopa. In addition, the blunted growth-hormone response to clonidine in depressed patients is particularly robust in those who have recently attempted suicide. Clearly, further work in this area is warranted, especially in the context of several reports of alterations in basal growth-hormone secretion in this disorder. The nature of this alteration is a reduction in the normal nocturnal rise in growth-hormone secretion, though this is not a universally agreed-upon ﬁ  nding. Alterations in growth-

hormone secretion in other psychiatric disorders (particularly schizophrenia) have also been reported, though the results may have largely been due to long-term treatment of such patients with dopamine-receptor antagonists, antipsychotic drugs.
The secretion of growth hormone and the regulation of this 
axis are distinct from that of the other endocrine axes for several reasons. First, this is the one axis in which two hypothalamic-hypophysiotrophic hormones have unequivocally been shown to play a physiological role. The ﬁ  rst discovered was somatostatin
orgrowth hormone-inhibiting hormone . It is distributed in the

orgrowth hormone-inhibiting hormone . It is distributed in the 
CNS not only in cells of the periventricular nucleus of the hypo-thalamus, which projects to the median eminence, but in a variety of extrahypothalamic areas as well. Indeed, somatostatin is known to function as a CNS neurotransmitter and is of particular interest to psychiatrists because of its early involvement in the Alzheimer’s disease process. Our group and others have documented the marked reduction in somatostatin concentrations in this dementing disorder.
(33) In addition, somatostatin concentrations 
are markedly elevated in the basal ganglia of patients with Huntington’s disease;
(35) the pathological implications of this 
ﬁ nding remain obscure. In contrast to the other peptide receptors 
described above in which one or at most two receptor subtypes have been identiﬁ  ed, several distinct somatostatin receptor sub-
types have now been structurally identiﬁ  ed. Such diversity suggests

types have now been structurally identiﬁ  ed. Such diversity suggests 
the possibility of speciﬁ  c receptor-subtype agonists and antagonists 
as putative therapeutic agents.
Several years after the elucidation of the structure of somatosta-
tin, the long-postulated growth hormone-releasing factor  (GHRF )
was found. This peptide has the most limited CNS distribution of all the hypothalamic-releasing hormones thus far studied. The vast majority of the peptide is found in the arcuate nucleus of the hypo-thalamus from where it projects nerve terminals to the median eminence. Unlike the other axes, the growth-hormone axis is also 
unique in not having a single target endocrine gland. Indeed, 
growth hormone does stimulate the release of somatomedin C

from the liver and it also exerts direct effects on a variety of targets including bone and muscle. Most, but not all, investigators have reported a blunted growth-hormone response to GHRF in depressed patients, but the total number of patients studied pales in comparison to the TRH- and CRF-stimulation test data. There are no data published on somatomedin C responses to GHRF in depressed patients. No published studies are available in which GHRF concentrations or GHRF-mRNA expression have been stud-ied in postmortem tissue of depressed patients and matched con-trols, an obvious study in view of the data reviewed above.The hypothalamic-pituitary-gonadal axis

In view of the remarkable gender differences in the prevalence rate of depression, the relatively high rates of postpartum depression, as well as the reduction in libido that is so characteristic of depres-sion, it is plausible to posit a reduction in HPG axis activity in depressed patients. Therefore, it is somewhat surprising that so little research has been conducted on HPG axis activity in depression and other psychiatric disorders. Indeed, a comprehensive database on this extraordinarily important area is simply not available, but the ﬁ eld has been reviewed.
(36) A series of older studies documented 
no differences in basal gonadotrophin levels in depressed patients when compared to controls. The gonadotrophin-releasing hor-
mone  (GnRH ) stimulation test has only been administered to a 
relatively small number of depressed patients; although the results revealed a blunted or normal response, no ﬁ  rm conclusions can be

relatively small number of depressed patients; although the results revealed a blunted or normal response, no ﬁ  rm conclusions can be 
drawn from this limited data set. Indeed, such studies require control for menopausal status, menstrual-cycle phase, use of oral contraceptives, as well as the measurement of baseline progester-one, oestrogen, and gonadotrophin plasma concentrations. One remarkable ﬁ  nding relevant to these questions is the remarkable 
effectiveness of the GnRH agonist, leuprolide, in the treatment of the premenstrual syndrome. It is believed to act by producing a chemical ovariectomy through a marked downregulation of 
adenohypophyseal GnRH receptors and the expected resultant

adenohypophyseal GnRH receptors and the expected resultant 
reduction in gonadotrophin and gonadal steroid secretion. Long-term treatment with this compound could theoretically result in bone-density reductions and a risk of cardiovascular disease. Therefore, supplementation with oestrogen and progesterone has been suggested in combination with leuprolide, though there are reports that such a strategy reduces the effectiveness of the treatment.
GnRH was the second of the hypothalamic-hypophysiotrophic

GnRH was the second of the hypothalamic-hypophysiotrophic 
hormones to be chemically characterized. It is relatively limited in distribution to hypothalamic regions and to the preoptic area and septum. It stimulates the secretion of both luteinizing hormone and follicle-stimulating hormone in both men and women. GnRH is known to act by stimulating GnRH receptors in the anterior pituitary gland, which results in the increased synthesis and release of the pituitary gonadotrophins, in turn causing the release of oestrogen and progesterone in women and testosterone in men. There is some evidence that oestrogens, which have receptors local-ized extensively throughout the CNS, may possess some antide-pressant activity, in perimenopausal and postpartum depression, though the data is far from clear.
(37) There are hints from the clini-
cal trial literature that postmenopausal women on oestrogen replacement may respond better to treatment with ﬂ  uoxetine than

cal trial literature that postmenopausal women on oestrogen replacement may respond better to treatment with ﬂ  uoxetine than 
women who are not receiving such treatment,
(38) though the data-
base is small and fraught with many confounds. Further, emphasiz-ing the potential role of sex steroids in affective disorders is the clini-cal study that demonstrates that in hypogonadal depressed men, testosterone treatment possessed antidepressant properties.
(39)
The hypothalamic-prolactin axis
Prolactin, a pituitary hormone which acts on the mammary gland, plays a critical role in lactation. Unlike the other axes described, this axis is unique in having a non-peptide release-inhibiting factor, dopamine. In addition, although there is relatively strong 2.3.3 neuroendocrinology

SECTION 2  the scientific basis of psychiatric aetiology 166
evidence for the existence of a prolactin-releasing factor, its isola-
tion and characterization has not yet been realized. One of the difﬁ culties in completing this task is the presence of TRH, which is 
a potent prolactin-releasing factor, and may in fact function physi-ologically in this regard. Interestingly, although the TSH response to TRH in depressed patients is often blunted, the prolactin response is not. Although the results are not unequivocal, most studies have not observed alterations of prolactin secretion in depressed patients.
(40) In contrast to this small database is a remark-
ably large database on the use of provocative tests of prolactin secretion in patients with psychiatric disorders. T o summarize brieﬂ  y, the prolactin response to agents that increase serotonergic 
neurotransmission such as l-tryptophan, 5-hydroxytryptophan (5-HTP), l-( +)- and d-( +)-fenﬂ  uramine, clomipramine, and also

neurotransmission such as l-tryptophan, 5-hydroxytryptophan (5-HTP), l-( +)- and d-( +)-fenﬂ  uramine, clomipramine, and also 
to direct serotonin-receptor agonists, is blunted in depressed patients, as well as in patients with cluster-B personality disorder and borderline personality disorder. The available data would sug-gest that this blunted prolactin response is mediated by alterations in 5-HT1A-receptor responsiveness.
Discussion and summary
Although, the hypothesis that the neuroendocrine window strategy would ultimately provide the long searched for information con-cerning the nature of monoamine circuit alterations in patients with psychiatric disorders has never been realized, the approach has led to major advances in biological psychiatry. It has led to the CRF hypothesis of depression , which is supported by a consider-
able multidisciplinary database, and this in turn has directed the ﬁ eld towards the development of novel therapeutic approaches,

able multidisciplinary database, and this in turn has directed the ﬁ eld towards the development of novel therapeutic approaches, 
namely CRF receptor antagonists. It also apparently explains the neurobiological mechanisms responsible for the increase in depres-sion (ﬁ  rst postulated by Freud in the early part of the 20th century) 
in patients exposed to trauma during their early life. If CRF is indeed the ‘black bile’ of depression, responsible for the endo-crinopathy of depression, as well as several of the other cardinal 
features of this disorder, then CRF-receptor antagonists should 
represent a novel class of antidepressants that will be a welcome addition to the armamentarium. Indeed, a number of pharmaceutical companies are now testing CRF-receptor antagonists as novel anxio-lytics and antidepressants in preclinical studies and clinical trials.
In addition to the now widely replicated HPA axis and CRF

In addition to the now widely replicated HPA axis and CRF 
alterations in depression, are the HPT axis abnormalities. Most depressed patients, in fact, exhibit alterations in one of these two axes. Furthermore, there is the widely replicated blunting of the growth-hormone response to clonidine and other provocative stimuli and the blunted prolactin response to serotonergic stimuli in depressed patients. The vast majority of studies have focused on patients with mood disorders, particularly unipolar depression. Clearly other disorders, including eating disorders, anxiety disor-ders, schizophrenia, and axis II diagnoses should also be critically evaluated and compared to the literature on depression. The original neuroendocrine window strategy may well have failed in terms of gleaning information about monoamine-circuit activity, but the mechanistic studies that followed have been remarkably fruitful. As repeatedly noted above, the availability of ligands that

can be utilized with positron-emission tomography to deter mine 
peptide-receptor alterations in the brain and pituitary of patients with psychiatric disorders will advance the field, as will the long-elusive ability to measure receptors for the endocrine target 
hormones (glucocorticoids, oestrogens, thyroid hormones, etc.) in the brains of patients with these severe mental illnesses.
Finally, it is important to note the increasing database suggesting 
that depression is a systemic disease with major implications for vulnerability to other disorders. Thus, depressed patients are much more likely to develop coronary artery disease and stroke, and perhaps cancer. They have been shown to have reduced bone 
density, rendering them more at risk for hip fracture and increasing 
a variety of measures of inﬂ  ammation. Such ﬁ  ndings may well be

a variety of measures of inﬂ  ammation. Such ﬁ  ndings may well be 
mediated by the described endocrine alterations in depression. This should provide a further impetus for investigating the neuroendocrinology of psychiatric disorders.
Psychoneuroendocrinology  http://www.elsevier.com/wps/ﬁ  nd/
journaldescription.cws_home/473/description#description
Hormones and Behavior  http://www.elsevier.com/wps/ﬁ  nd/
journaldescription.cws_home/622842/description#description
Neuroendocrinology  http://content.karger.com/ProdukteDB/produkte.
asp?Aktion =JournalHome&ProduktNr =223855
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Nemeroff, Charles B (3-27-08)
Research Grants
NIH
Scientiﬁ  c Advisory Board
AFSP; AstraZeneca; Forest Laboratories; NARSAD; Quintiles; Janssen/
Ortho-McNeil, PharmaNeuroboost, Mt. Cook Pharma, Inc 
Stockholder or Equity
Corcept; Revaax; NovaDel Pharma; CeNeRx, PharmaNeuroboost
Board of Directors
American Foundation for Suicide Prevention (AFSP); George West Mental 
Health Foundation; NovaDel Pharma, Mt. Cook Pharma, Inc
Patents

Patents
Method and devices for transdermal delivery of lithium (US 6,375,990 B1)
Method to estimate serotonin and norepinephrine transporter occupancy 
after drug treatment using patient or animal serum (provisional ﬁ  ling 
April, 2001)
Neigh, Gretchen N. (7-11-08)
NIH, NARSAD, AHA2.3.3 neuroendocrinology

SECTION 2  the scientific basis of psychiatric aetiology 168
2.3.4 Neurotransmitters 
and signalling
By the end of the 19th century it was recognized that signalling 
from one neurone to the next occurs at specialized contacts – Sherrington coined the term ‘synapse’ . It took another 50 years for scientists to accept that information passes between neurones prin-cipally through the movement across synapses of chemicals and not electrical current. T oday changes in chemical transmission at brain synapses are accepted as being key to the successful drug treatment, and cause, of many forms of psychiatric illness. This article focuses on general aspects of chemical transmission and describes some recent advances relevant to psychiatry that point the direction of future research.
Otto Loewi identiﬁ  ed the ﬁ  rst chemical neurotransmitter, acetyl-

choline, in 1921. T oday evidence suggests that there are many tens if not hundreds of molecules in the brain that have neurotransmit-ter properties. These molecules include not only the three major 
classes of neurotransmitters—amines, amino acids and neuropep-
tides—but also speciﬁ  c purines, trophic factors, inﬂ  ammatory 
mediators (chemokines and cytokines), lipids, and even gases. Examples of molecules that serve neurotransmitter functions in the brain are listed in Table 2.3.4.1. This list is not exhaustive and more are likely to be discovered.
Basic principles of chemical transmission
Typically a molecule is classiﬁ  ed as a neurotransmitter if it is local-

ized in neurones, released from nerve terminals (and often soma and dendrites) on membrane depolarization, and exerts physiolog-ical and molecular effects through acting on postsynaptic receptors. However, the degree to which a particular molecule satisﬁ  es these 
criteria may vary. For example, the term ‘neurotransmitter’ was once used to cover only those molecules that exert fast synaptic effects, whereas molecules that exerted slow synaptic effects were termed ‘neuromodulators’ . These distinctions are less useful today (and will not be used herein) as it is recognized that many molecules are capable of exerting both fast and slow synaptic effects, depending on the receptor activated. Moreover, it is now recognized that certain molecules transfer information at a synapse in a ‘retrograde’ direction. In this case the molecules are located

in the postsynaptic neurone and, when their synthesis is activated, 
the molecule diffuses across the synapse to act presynaptically.
The general principles of the chemical transmission at central 
synapses are similar across all neurotransmitter molecules but there are often important differences between molecules especially across molecules of different size, in particular small molecule transmitters such as amines and amino acids, and peptides (Fig. 2.3.4.1).
(1)
Small molecule neurotransmitters
Typically small neurotransmitter molecules such as amines and amino acids are synthesized at the nerve terminal by one or a few enzymatic steps and packaged in small vesicles via proton-coupled vesicular transporters, prior to release into the synapse on arrival of

a depolarizing action potential. After release, the neurotransmitter diffuses across the synapse to interact with receptors on the post-synaptic neurone to trigger electrical and/or biochemical changes in the postsynaptic cell. Small molecule neurotransmitters are also released from the soma and dendrites of neurones, one purpose being to interact with presynaptic receptors that signal negative feedback to the neurone.
Once released the small neurotransmitters are selectively 
taken up by sodium-coupled transporters that are located in the plasma membrane of the nerve terminal or neighbouring cells (neurones or glial cells). This transport terminates transmission at the postsynaptic receptor, maintains low extracellular levels of transmitter, and allows reuse of the neurotransmitter by the neurone. Transport into the nerve terminal also presents the trans-
mitter to catabolic enzymes to generate biologically inactive metab-

olites, for instance, monoamine oxidase in the case of the amine transmitters.
Neurotransmitter transporters
Advances in cloning technology has lead to new discoveries regard-ing the structural and pharmacological identity of transporters located on the plasma membrane, as well as vesicular transporters Table 2.3.4.1  Examples of neurotransmitters in the brain
Chemical class Example
Amines Dopamine
Noradrenaline
5-hydroxytryptamine
HistamineMelatonin
Acetylcholine
Amino acids γ-aminobutyric acid (GABA)
Glutamate
Glycine
Neuropeptides Substance P
Leu- and Met-enkephalin
Galanin
Purines Adenosine
Adenosine triphosphate (ATP)
Neurotrophic factors
#Neurotrophins (e.g. BDNF, NGF)
Insulin-like growth factor (IGF)
Vascular endothelial growth factor (VEGF)
Cytokines* Interleukin-1 (IL-1)
Tumor necrosis factor- α (TNF- α)
Chemokines* CC Chemokines (e.g. Interleukin-8 [IL-8])
CXC Chemokines
Endocannabinoids#Anandamide

2-Arachidonyl-glycerol (2-AG)
Gases#Nitric oxide (NO)
Carbon monoxide (CO)
*Putative class of neurotransmitters.
#Retrograde messengers.

169
located inside the nerve terminal.(2) The latter transporters 
concentrate transmitters in synaptic vesicles prior to release and play a key role in determining the neurotransmitter phenotype of a neurone.
(3) A summary of plasma membrane and vesicular 
transporters is given in Table 2.3.4.2.
Plasma membrane transporters
Speciﬁ  c plasma membrane transporters for the amine neurotrans-
mitters, dopamine (DAT), noradrenaline (NET), 5-HT (SERT), have been identiﬁ  ed, sequenced and, investigated in detail at the 
molecular level because they are the site of action of stimulants such as amphetamines and cocaine, as well as many antidepressant drugs.
(2) Indeed, the drug-binding site and the precise molecular 
mechanism of transporter inhibition by tricyclic antidepressant drugs have recently been revealed.
(4)Molecular cloning techniques have uncovered the genes for four

(4)Molecular cloning techniques have uncovered the genes for four 
transporters for the inhibitory neurotransmitter GABA; GAT-1, GAT-2, GAT-3 and BTG-1, the latter being localized primarily in the kidney. These transporters are highly homologous but pharma-cologically distinct, with GAT-1 and GAT-3 being the most abun-dant subtypes and present on both neurones and glial cells. Although the signiﬁ  cance of these transporters is yet to be fully 
understood, they display overlapping but different expression pat-terns in the CNS, suggesting distinct functional roles. The anticon-vulsant effect of tiagabine is likely mediated by blockade of GAT-1, and there is much scope for new GABA uptake inhibitors of as yet unclear utility.
Glycine, another inhibitory amino acid transmitter, also has spe-
ciﬁ c transporters located preferentially on the plasma membranes

ciﬁ c transporters located preferentially on the plasma membranes 
of glial cells in the forebrain (GLYT1) and neurones of the hind-
brain and spinal cord (GLYT2). Interestingly, glycine is a positive 
allosteric co-modulator of glutamate NMDA receptors, and glycine Fig. 2.3.4.1 Summary of the principal steps involved in chemical neurotransmission in the brain. Neuropeptides are 
synthesized in the cell body and then packaged in large dense core vesicles (LDCVs) that are transported into axons and dendrites (1). Small ‘classic’ neurotransmitters (e.g. amines and a mino acids), are synthesized at the nerve terminal and store d 
in synaptic vesicles, and released into the synaptic cleft (2). LDCVs contain proteolytic enzymes (convertases) that generate 
the active neuropeptide from the precursor. Neurotransmitter receptors are either of the G-protein-coupled (metabotropic)

or ligand-gated ion channel (ionotropic) type and are present on cell soma, dendrites, axons, and nerve endings (1,4). The small neurotransmitters are released during low and high frequency ﬁ  ring, whereas neuropeptides are preferentially released under burst or high frequency ﬁ  ring (2–4). Small transmitters have reuptake mechanisms (transporters) at both the plasma membrane and the vesicle membrane (5), which terminate neurotransmitter action and allow recycling (4). In contrast, neuropeptides are broken down by extracellular peptidases (6), and replacement occurs via axonal transport. Glial cells can express neurotransmitter receptors and transporters (7). Receptors are trafﬁ  cked to and from the cell membrane by G-protein interacting proteins (8). Reprinted from The Lancet Neurology, 2, Hokfelt T, Bratfai T, Bloom F, Neuropeptides: opportunities for drug discovery, 465, copyright 2003, with permission from Elsevier.
Somatic
releaseDendritic
release
Break
downGlial
cells1
2
36

Somatic
release
Break
downGlial
cells1
2
36
45
8
LDCV
Synaptic vesicle with classic transmitter
GPCR for peptide or classic transmitter
Transporter for classic transmitter
Ionotropic receptor for classic transmitter7
Dendritic
peptide
synthesis
Low
frequency
Low frequencyHigh
frequencyor burst firing
High frequency
burst firingExtrasynaptic
release
Synapse
Postsynaptic
density
Classic
transmitter2.3.4 neurotransmitters and signalling

SECTION 2  the scientific basis of psychiatric aetiology 170
transport blockade may offer a means to facilitate the functioning 
of this receptor without incurring excitotoxic effects. The antipsy-chotic potential of glycine transport blockers is currently under investigation because of consistent evidence of a link between the symptoms of schizophrenia and low glutamate function.
(2)
Four transporters for the excitatory amino acid neurotransmit-
ter, glutamate, have been cloned; EAAT1 (excitatory amino acid transporter1; synonym GLAST), EAAT2 (synonym GLT1), EAAT3, EAAT4, and EAAT5.
(5) These transporters are located on both neu-
rones (EAAT3) and glial cells (predominantly EAAT1/2) and serve 
to maintain low extracellular concentrations of glutamate, as well as providing a source of intracellular glutamate for metabolism. Whilst pharmacological blockade of glutamate transport increases excitotoxicity, pharmacologically enhanced EAAT expression appears to be neuroprotective.
(6)

(6)
Vesicular transporters
Vesicular monoamine transporter 2 (VMAT2) has been identiﬁ  ed 
and shown to be present in neurones of dopamine, noradrenaline and 5-HT (and histamine). In addition, vesicular monoamine 
transporter 1 (VMAT1) is an integral protein in the membrane of 
secretory vesicles of neuroendocrine and endocrine cells. Reserpine is a blocker of VMAT and causes depletion of amines, and the drug’s tranquillizer effects are directly linked to this action. Acetylcholine is loaded into synaptic vesicles by a distinct trans-porter, V AchT.
Three homologous vesicular transporters for glutamate, 
VGLUT1, VGLUT2, and VGLUT3, have been cloned and character-ized at the molecular level. Whilst all possess similar molecular 
properties, they are expressed on different neurone populations.
(3)

(3)
Interestingly, VGLUT3 is found in amine-containing neurones, raising the possibility of glutamate being a co-transmitter in these neurones. The vesicular transporter for GABA is VGAT. Loss of VGAT causes a drastic reduction in release of not only GABA but also glycine, indicating that glycinergic neurones do not express a separate vesicular glycine transporter.
Neuropeptides
Following the chemical identiﬁ  cation of the ﬁ  rst neuropeptide 
Substance P in 1971, evidence has accumulated that numerous peptides play neurotransmitter roles in the brain.
(1) Some examples 
are shown in Table 2.3.4.3. The neuropeptides comprise 3–100 a mino

acids and together with other putative signalling peptides such as growth factors and cytokines, are synthesized in the nucleus by DNA transcription followed by translation from mRNA into precursor polypeptides (Fig. 2.3.4.1). These precursors typically undergo extensive post-translational processing that includes cleavage into smaller peptides by endopeptidases as well as other enzymic modi-ﬁ cations. The precursor peptide usually contain an N-terminal 
signal sequence that directs the transport of newly synthesized pro-tein to the lumen of the endoplasmic reticulum, and then the Golgi complex where the peptide is packaged into vesicles (so called large dense core vesicles) that are transported along the axon to the synapse. This obviates the need for neuropeptide vesicular transporters.

Proteolytic processing of a single precursor peptide often gener-
ates not one but a family of biologically active peptides, although the proteolytic steps may be tissue-speciﬁ  c. The opioid peptides provide 
one of the best worked out examples of this form of processing. Proopiomelanocortin (POMC) is a hypothalamic precursor opioid peptide whose structure contains sequences for adrenocorticotropic hormone (ACTH), α-melanocyte stimulating hormone ( α-MSH)
andβ-endorphin. In the anterior lobe of the pituitary gland POMC 
is processed to form ACTH, whilst in the intermediate lobe POMC is processed to form α-MSH and β-endorphin. On the other hand,

is processed to form ACTH, whilst in the intermediate lobe POMC is processed to form α-MSH and β-endorphin. On the other hand, 
post-translational processing of the opioid precursor peptide, pro-enkephalin, gives rise to multiple copies of the pentapeptide met-enkephalin as well as a copy of leu-enkephalin, whilst a third opioid precursor, prodynorphin, gives rise to dynorphin. In total, the 3 separate opioid peptide genes give rise to at least 18 endogenous peptides with opiate-like activity.
Multiple proteolytic enzymes have been cloned and extensively 
characterized, including prohormone convertases that produce striking phenotypic effects when genetically manipulated in mutant mouse models.
(7) The therapeutic utility of pharmacological

(7) The therapeutic utility of pharmacological 
manipulation of neuropeptide synthesis and degradation in the brain has yet to be realized. However, the success of inhibitors of the prohormone convertase that synthesizes angiotensin in the periphery (ACE inhibitors), for the treatment of hypertension, sets an important precedent.
Another mechanism to generate neuropeptide diversity is 
through alternative RNA splicing of a single gene. For example, in the case of the tachykinins alternative splicing of preprotachykinin gene A mRNA results in 3 splice variants which, after translation and post-translational processing, collectively generate the ﬁ  ve 
biologically active peptides of the tachykinin family (including Substance P).Table 2.3.4.2  Example of neurotransmitter transporters in the brain
Neurotransmitter Transporter name

Dopamine
5-Hydroxytryptamine
GABA
Glutamate
Glycine
Acetylcholine (choline)DAT
NET
SERT
GAT-1
GAT-2
GAT-3
BGT-1 (primarily in kidney)EAAT-1 (GLAST1)
EAAT-2 (GLT-1)
EAAT-3 (EAAC1)EAAT-4
EAAT-5
GLYT-1GLYT-2
CHT
Monoamines (dopamine, noradrenaline, 5-HT, histamine)
GABA
Glutamate
AcetylcholineVMAT1
VMAT2
VGAT
VGLUT1
VGLUT2
VGLUT3
VAchT

171
T o date, there is little evidence that neuropeptides are cleared 
from the synapse by transporters in the plasma membrane, indicat-ing that these particular transmitters are not recycled after release. 
Rather, evidence suggests that their action is terminated by peptidases that are thought to be located on extracellular mem-branes. Thus, replenishment of neuropeptides during high levels of synaptic activity is dependent on the proteolytic enzymes that generate the active peptides in the neurones.
A feature of most if not all neuropeptides is their co-localization 
with classic neurotransmitters. Some of the best examples include co-localization between GABA/dynorphin in movement control pathways (striatonigral neurones), CCK/dopamine in reward path-ways (mesoaccumbens neurones), and glutamate/Substance P in pain pathways (dorsal root ganglion neurones). The functional signiﬁ  cance of this co-localization is not fully clear but evidence

suggests that peptide release requires higher frequencies of neuro-nal discharge than classic transmitters, and once released the neu-
ropeptide either facilitates or opposes the function of the co-localized 
transmitter.
(1) In a recent example, co-localization between 5-HT 
and galanin in midbrain raphe neurones was investigated to reveal an action of the peptide on 5-HT feedback mechanisms. This knowledge has been exploited to develop galanin ligands that are under development as novel antidepressant strategies.
(8)
Neurotrophic factors are brain peptides that were originally recog-nized for their role in supporting growth, differentiation and sur-vival of neurones but today are thought to possess many of the properties of neurotransmitters including neuronal localization and release, and an ability to modulate synaptic function. Moreover, there is evidence that trophic factors signal in a retrograde fashion

(see later). Neurotrophic factors are currently named according to the action with which they were originally characterized (brain-derived neurotrophic factor — BDNF, nerve growth factor — NGF) and they comprise many families.
(9)
Certain features distinguish neurotrophic factors from neuro-
peptides (see above). In particular, neurotrophic factors are larger molecules; for example, BDNF has a molecular size of 14 kDa whereas neuropeptides are typically much smaller peptides. Also whilst neuropeptides signal via G-protein coupled receptors (see below), neurotrophic factors signal via direct activation of a class of transmembrane spanning protein kinases called protein tyrosine kinases (Trk receptors) of which four types have been identiﬁ  ed so 
far (TrkA, TrkB, TrkC and p75), and that phosphorylate proteins on tyrosine residues.
(10) In some cases, the neurotrophic factor

(10) In some cases, the neurotrophic factor 
receptor and protein tyrosine kinase reside in the same protein, while in other cases, the receptor recruits an intracellular protein tyrosine kinase. Speciﬁ  c neurotrophic factors signal via speciﬁ  c 
protein kinases (e.g. NGF – via TrkA, BDNF – via TrkB). Activation of the protein tyrosine kinase triggers cascades of further protein phosphorylation that produce not only trophic effects but also changes in synaptic transmission.
Much recent interest in neurotrophic factors derives from ﬁ  nd-

ings that they regulate synaptic transmission in the adult brain, and that neurotrophic factor expression can be modulated through interactions with amine and amino acid neurotransmitters. For example, evidence suggests that repeated administration with amine-targeted antidepressants increases BDNF expression in animal models and depressed patients, whereas decreases in BDNF have been linked to depression. These data contribute to a currently popular hypothesis that changes in BDNF are important to the symptoms of depression as well as the relief of these symptoms by antidepressant drug treatment.
(11, 12)
Chemokines and cytokines
Chemokines and cytokines comprise large families of homologous small proteins (6–10 kDa) and differ from neuropeptides and neu-rotrophic factors in that they are key signalling molecules of the immune system. However, recent ﬁ  ndings suggest that these mole-

cules and some of their receptors are also present in the brain in both glial cells and neurones, raising the possibility that they might also have neurotransmitter-like functions. Although the evidence is incomplete, data show that chemokine and cytokine molecules have several of the characteristics that deﬁ  ne neurotransmitters 
including modulation of release of other neurotransmitters or neu-ropeptides.
(13) The pharmacological development of agonists and 
antagonists that are selective for chemokine and cytokine receptors and can cross the blood-brain barrier, would open an intriguing new era of research in neuroscience.
Retrograde messengers

It is now recognized that in contrast to classical neurotransmitters and neuropeptides, a small number of brain molecules signal infor-mation at a synapse in a ‘retrograde’ direction that is released from the postsynaptic neurone to act on the presynaptic neurone. Molecules falling into this category include certain neurotrophic factors (see above), gaseous molecules and lipid messengers.Table 2.3.4.3  Examples of families of neuropeptides
Opioid peptides Leu-enkephalin
Met-enkephalin
Dynorphin
β-endorphin
Nociceptin
Tachykinins Substance P
Neurokinin A
Neurokinin B
Hypothalamic releasing factors Thyrotrophin releasing factor (TRH)
Corticotrophin releasing factor (CRF)
Growth hormone releasing hormone (GHRH)
Gut-brain peptides Cholecystokinin (CCK)
Galanin
Insulin

Galanin
Insulin
NeurotensinNeuropeptide Y (NPY)
Vasointestinal polypeptide (VIP)
Other peptides Bradykinin
Calcitonin gene-related peptideMelanin concentrating hormone (MCH)
Melanocortin
OrexinOxytocin
Vasopressin2.3.4 neurotransmitters and signalling

SECTION 2  the scientific basis of psychiatric aetiology 172
Nitric oxide
One putative retrograde gaseous messenger is nitric oxide (NO) 
that is produced in neurones from the amino acid L-arginine by a neurone-speciﬁ  c isoform of NO synthase (NOS), which has a 
widespread abundance in the brain. The ﬁ  rst evidence of a role for 
NO as a neurotransmitter came from ﬁ  ndings that stimulation of 
glutamate NMDA receptors by glutamate caused the release of a diffusible messenger, which was subsequently identiﬁ  ed as NO.
(14)
The current thinking is that increased glutamatergic activity trig-

(14)
gers in postsynaptic neurones an NMDA-mediated activation of NOS, and then increased synthesis of NO that diffuses across the synapse to enhance presynaptic transmission. The latter occurs at least in part through NO acting on guanylate cyclase to increase production of the second messenger cGMP . In postsynaptic neu-rones, NO regulates certain protein kinase pathways and gene transcription factors, and also changes cell signalling events by S-nitrosylation.
On the basis of studies on the effects of NO donors, and pharma-
cological and genetic modulation of NOS, increased NO production is associated with a range of CNS functions including cognition, induction and maintenance of synaptic plasticity, and NO may be neuroprotective under some conditions.
(15) However, because

(15) However, because 
excess NO has neurotoxic potential, and because of the difﬁ  culty of 
delivering NO to the CNS without inducing side effects through the many actions of NO on peripheral tissues, the development of NO-based therapies for the treatment of CNS disorders will be very challenging.
Endocannabinoids
Examples of lipid retrograde messengers are the endocannabinoids, which are a recently discovered family of naturally occurring lipids (including anandamide) that interact with cell surface receptors that are targeted by Δ
9-tetrahydrocannabinol (THC). The latter is 
the principle biologically active constituent of marijuana, the dried leaves of the cannabis plant.
(16) In essence, endocannabinoids 
appear to be to THC what opiate peptides are to morphine.
It is now apparent that endocannabinoids are synthesized enzy-

mically on demand within the postsynaptic neurone and once pro-duced, diffuse across the synapse in a retrograde direction. Endocannabinoids then suppress neurotransmitter release through activation of presynaptic cannabinoid receptors, the main type in the brain being classiﬁ  ed CB
1 (analogous in terms of structure and 
function to opiate receptors but quite distinct pharmacologically).
Many of the central effects of THC, including analgesia, increased 
appetite and euphoria, are thought to be mediated by CB1 receptors. 
Since CB1 receptors have a powerful inﬂ  uence on synaptic transmis-
sion in the brain and have limited distribution in the periphery (although CB
2 receptors are abundant in the immune system),

2 receptors are abundant in the immune system), 
drugs targeting these receptors and/or the enzymes involved in endocannabinoid synthesis and metabolism may have interesting therapeutic possibilities. Such drugs are currently under investiga-tion as analgesic and anorectic agents, amongst many others.
Neurotransmitter receptors
Neurotransmitter receptors are located on the cell surface of both pre- and postsynaptic neurones, and as a general rule can be divided into two main types; one type activates an ion channel that is intrinsic to the receptor (ligand-gated ion channel, sometimes

called ionotropic receptor), the other type activates a GTP binding protein which acts as a transducer between the receptor and effec-tor system (G-protein coupled receptor [GPCR], sometimes called metabotropic receptor). An exceptions to this general rule are certain trophic factors and cytokines which signal via direct activation of a unique class of protein kinases, protein tyrosine kinases. In addi-tion, steroid hormones signal in the brain by crossing the plasma membrane and activating receptors in the neuronal cytoplasm that translocate to the nucleus where they bind DNA and function as transcription factors.
Ligand-gated ion channels typically comprise a multimeric plas-
ma membrane receptor complex (4–5 subunits each with 4 trans-membrane spanning domains) that gate the inﬂ  ux of ions to evoke

ma membrane receptor complex (4–5 subunits each with 4 trans-membrane spanning domains) that gate the inﬂ  ux of ions to evoke 
fast changes in synaptic signalling. GPCRs comprise a superfamily of single proteins (7 transmembrane spanning domains) that evoke slower changes in synaptic signalling through the generation of second messengers and interactions with intracellular signalling pathways.
One of the most remarkable advances in molecular neurophar-
macology in the last 20 years, which has been made possible through advances in molecular cloning technology and the virtual completion of the human genome project, has been the discovery of huge diversity in neurotransmitter receptors. This complexity takes the form of not only several hundred GPCRs
(17) but also con-
siderable heterogeneity in ligand-gated ion channels produced through the assembly of multiple receptor subunits.
(18, 19)

(18, 19)
Most, and probably all, neurotransmitters have more than one 
receptor type, which were once classiﬁ  ed solely according to their 
pharmacological properties, but today are grouped more precisely in terms of their pharmacological, functional, and structural proper-ties. Many neurotransmitter receptor subtypes have been cloned and their distribution within the brain is known; the challenge is to turn these advances at the molecular level into a better understanding of synaptic function, and novel therapies. Neurotransmitter receptors are too numerous to describe individually but examples are shown in Table 2.3.4.4 and recent detailed reviews are available elsewhere.
(10)
Ligand-gated ion channels

(10)
The amino acids glutamate and GABA are, respectively, the princi-pal fast excitatory and inhibitory transmitters in the brain and exert their effects via ligand-gated ion channels. However, other trans-mitters are also capable of fast transmission via ligand-gated ion channels and these include acetylcholine (nicotinic receptors), 5-HT (5-HT
3) and ATP (P2X). However, to date there is no known 
neuropeptide with a ligand-gated ion channel.
Ligand-gated ion channels for glutamate
Glutamate elicits fast excitatory effects by activating ligand-gated ion channels on postsynaptic membranes of which there are three types; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 
(AMPA) receptors, N-methyl-d-aspartate (NMDA) receptors and 
less abundant kainate receptors, all of which were originally named 
according to their preferred synthetic agonist and gate cations (Na
+,
K+, and Ca2+) with varying degrees of selectivity. There is likely to

+,
K+, and Ca2+) with varying degrees of selectivity. There is likely to 
be additional heterogeneity because each receptor can be assem-bled as a tetramer of one or more of multiple subunits. For instance, AMPA receptors can be formed from tetramers of combinations of

173
Table 2.3.4.4  Examples of neurotransmitter receptors
Transmitter Receptor Signal transduction
Dopamine D1 family (Dopamine D1, D5)
D2 family (Dopamine D2, D3, D4)Adenylate cyclase (Gs)
Adenylate cyclase (Gi/o)
Noradrenaline α1 family ( α1A,B,D )
α2 family ( α2A,B,C)
β family ( β1,2,3)Phospholipase C (Gq)
Adenylate cyclase (Gs)
5-hydroxytryptamine 5-HT1 family (5-HT1A, B, D,E, F)
5-HT2 family (5-HT2A, B, C)
5-HT3
5-HT4
5-HT5 family (5-HT5A, B)
5-HT6
5-HT7Adenylate cyclase (Gi/o)
Phospholipase C (Gq)
Cation channelAdenylate cyclase (G
s)
Not certain
Acetylcholine M1 (muscarinic)
M2
M3
M4
M5
Nicotinic ( α1–10, β1–4, δ, ε, γ)Phospholipase C (Gq)
Cation channel
GABA GABAA (α1–6, β1–3, γ1–3, σ1–3, δ, ε, π, o)
GABABChloride channelAdenylate cyclase (G
i/o)
Glutamate AMPA (GluR1–4)
NMDA (NR1, NR2A–D, NR3A–B)

i/o)
Kainate (GluR5–7, KA1, KA2)
Group I family (mGluR1/5)
Group II family (mGluR2–3)
Group III family (mGluR4,6,7,8)Cation channel
Tachykinin (including  substance P) NK1
NK2
NK3Phospholipase C (Gq)
Opioid δ
κ
μAdenylate cyclase (Gi/o)
Galanin GAL1
GAL2GAL3Adenylate cyclase (G
i/o)
Adenosine A1
A2 family (A2A, B)
A3Adenylate cyclase (Gi/o)
ATP P2X family (P2X1-7)
P2Y1
P2Y2
P2Y4
P2Y6
P2Y11
P2Y12
P2Y13
P2Y14Cation channelPhospholipase C (G
q)

P2Y1
P2Y2
P2Y4
P2Y6
P2Y11
P2Y12
P2Y13
q)
Cannabinoid CB1
CB2Adenylate cyclase (Gi/o)
Adenylate cyclase (Gi/o)2.3.4 neurotransmitters and signalling

SECTION 2  the scientific basis of psychiatric aetiology 174
four subunits (GluR1−GluR4) and NMDA receptors from two 
subunits (NR1, NR2). There are a large number of naturally occur-ring variants of both AMPA and NMDA subunits generated through RNA editing and alternative splicing.
The pharmacological and functional signiﬁ  cance of this com-
plexity is not yet clear although evidence suggests that certain agents are able to distinguish between different receptor assem-blies.
(10) Interestingly, recent data suggest that changes in AMPA 
receptor subunit composition at the postsynaptic membrane cause differences in ion (Ca
2+) permeability that change synaptic efﬁ  cacy, 
the best-characterized form of which is long-term potentiation (LTP), a widely accepted neurophysiological correlate of learning and memory.
(19)
An interesting feature of many ligand-gated ion channels is the

(19)
An interesting feature of many ligand-gated ion channels is the 
presence of multiple chemically-sensitive sites (allosteric modula-tory sites), in addition to the site(s) which bind the natural trans-mitter ligand. This is the case for both the AMPA and NMDA receptors. Thus, in addition to the glutamate binding site AMPA receptors are sensitive to ‘AMPAkines’ which comprise a chemically diverse group of agents that potentiate the function of the receptor inin vitro  models, and elicit associated procognitive effects 
in vivo .
(20) Non-glutamate sites on the NMDA receptor include a 
site for Mg2+ that is the source of a voltage-dependent NMDA

in vivo .
site for Mg2+ that is the source of a voltage-dependent NMDA 
receptor block which requires membrane depolarization to open, as well as positive modulatory sites for glycine and polyamines. Whilst glutamate is released from presynaptic terminals in an activ-ity-dependent fashion and acts as a neurotransmitter, glycine and the polyamines act as extracellular modulators that are present at more constant levels. The latter binding sites are under investiga-tion as a possible source of NMDA receptor enhancing agents that do not suffer the potential excitotoxic effects of agonists at the glutamate site.
(21)
Ligand-gated ion channels for GABA
GABA elicits fast inhibitory effects by activating the GABAA receptor 
ion channel complex. GABAA receptors are heteropentameric mem-
brane proteins that form a GABA-gated chloride channel. There are at least 18 types of GABA
A receptor subunits ( α1–6, β1–3, γ1–3, ∏,

δ, θ and p1–3). Although studies co-expressing different GABAA
receptor subunits indicate the potential for several hundreds if 
not thousands of GABAA receptor subunit combinations, studies on 
GABAA receptor subunit distribution and abundance in native brain 
tissue indicate that the number of naturally occurring types of GABA
A receptors may be of the order of 10 or fewer.(22)
As with the glutamate ionotropic receptors, GABAA receptors 
have a number of allosteric modulatory sites including those sensi-tive to certain endogenous steroids, anaesthetic agents (for example alfaxalone) and alcohol (ethanol). However, the vast majority of GABA
A receptors are characterized by their sensitivity to benzodi-

azepines. Both genetic and medicinal chemistry approaches have been used to identify the pharmacological signiﬁ  cance of GABA
A
receptor subtypes, and speciﬁ  cally to determine whether the mul-
tiple behavioural effects of benzodiazepines such as diazepam (sedation, anxiolysis, amnesia, motor in-coordination etc.) can be attributed to speciﬁ  c GABA
A receptor subunit combinations.(18)
In particular, studies with point-mutated mice have revealed that 
the sedative effect of diazepam is mediated by α1-containing 
GABAA receptors, whereas the anxiolytic action is mediated by α2/
α3-containing GABAA receptors. Moreover, ﬁ  ndings that ligands with selective actions at α2- and/or α3-containing GABAA receptors 
display anxiolytic activity, raise the possibility of future benzo-diazepines with behaviourally selective actions. Interestingly, α5-containing GABA
A receptors may be an important site of action

A receptors may be an important site of action 
of alcohol. The GABAA receptor subunit(s) targeted by steroids 
and anaesthetics to produce the CNS inhibitory effects of these agents are currently under investigation.
G-protein coupled receptors
Almost all neurotransmitters signal effects via GPCRs and most neurotransmitters signal via more than one type of GPCR. For example, the amine 5-HT possesses 14 receptor subtypes (comprising seven receptor families, 5-HT
1–7), 13 of which are 
GPCRs and one is a ligand-gated ion channel. Each 5-HT GPCR has high afﬁ  nity and selectivity for 5-HT but individually the recep-
tors demonstrate different selectivity for other ligands, arise from different (but homologous) genes, and are formed from different protein sequences with different distributions and signalling effects.

(23) Since several 5-HT GPCRs can co-localize at a single 
synapse, the signal received by a postsynaptic neurone may be quite complicated. This complexity for 5-HT can be seen in many other transmitters including dopamine (D
1–5), glutamate (mGluR1–8), 
noradrenaline ( α1A,B,D ,α2A,B,C ,β1–3), endocannabinoids (CB1–2)
and neuropeptides (Table 2.3.4.4).
Typically GPCRs comprise a single membrane protein with seven 
transmembrane spanning domains, an N-terminus facing the extracellular space, a C-terminus facing the cytoplasm, and several intracellular transmembrane domain linking loops. The N-terminus of some GPCRs (mGluR
1–8, GABAB) contains the ligand binding 
site, while for most GPCRs the predicted ligand binding site lies within the transmembrane domains. Both the C-terminus and the third transmembrane intracellular loops are targets for phosphory-lation by protein kinases; the third intracellular loop is the main site of G-protein interaction.
G-proteins

Each G-protein is a heterotrimer comprised of α,β and γ subunits 
that dissociate on binding of ligand to the GPCR. On dissocia-tion, the α subunit binds GTP and through intrinsic GTPase 
activity directly regulates a number of specific downstream effector enzymes and ion channels. The β/γ subunits are also bio-
logically active and regulate some of the same effector proteins.
There are four major types of G-proteins, Gs, Gi, Gq and G
0 that 
produce the following signalling effects; activation of adenylate cyclase, inhibition of adenylate cyclase, activation of phospholipase C and interaction with Ca
2+ and K+ channels, respectively. Changes 
in the activity of adenylate cyclase results in altered intracellular levels of the ‘second messenger’ cyclic adenosine monophosphate (cAMP). Similarly, phospholipase C (PLC) alters intracellular lev-els of inositol triphosphate (IP
3) and diacyl glycerol (DAG). Altered

3) and diacyl glycerol (DAG). Altered 
levels of these second messengers trigger changes in activity of spe-ciﬁ c signalling cascades and ultimately changes in physiological 
responses (see below).
The opening of ion channels in response to neurotransmitter-
induced GPCR activation leads to direct effects (excitatory or inhibitory) on the electrical properties of neurones, albeit on a slightly slower timescale than effects produced by ligand-gated ion channels. Almost all neurotransmitter classes are able to evoke

175
changes in ion channel opening via GPCRs, and some may be 
clinically important. For example, the α2-adrenoceptor-induced 
opening of K+ channels on noradrenaline neurones that causes 
a fall in noradrenergic activity and release, may contribute to the anxiolytic and sedative properties of α
2-adrenoceptor agonists 
such as clonidine. On the other hand, the 5-HT2A receptor-induced 
closing of K+ channels on cortical neurones that causes an increase 
in cortical neurone activity, may underlie the psychotic effects of LSD and related hallucinogens.
(23)
GPCR regulation
Recent discoveries of interactions between GPCRs and other intra-cellular proteins have lead to a new understanding of how the recep-tors are regulated and trafﬁ  cked to and from the plasma membrane. 
Studies commencing on the β-adrenceptor, have identiﬁ  ed two 
families of regulatory proteins called β-arrestins and GPCR kinases

(GRKs). Within seconds of being activated by an agonist the GPCR is phosphorylated by a GRK on the C-terminal cytoplasmic tail and other intracellular domains. This phosphorylation promotes the interaction of β-arrestins with the GPCR, which limits the signal 
duration, and causes loss of sensitivity to agonist activation, and then receptor internalization from the cell surface.
(24)
In addition to β-arrestins the C-termini of GPCRs associate 
with a large variety of transmembrane or soluble proteins, termed ‘GPCR-interacting proteins’ (GIPs). Some GIPs are themselves GPCRs that form homo- or heterodimers, while other GIPs are ionic channels, ionotropic receptors and proteins that control 
GPCR trafﬁ  cking
(25). One interesting example of a GIP is the 
molecule p11, which reportedly functions to trafﬁ  c a 5-HT GPCR

molecule p11, which reportedly functions to trafﬁ  c a 5-HT GPCR 
(5-HT1B) to the plasma membrane. Evidence suggests that p11 
expression is reduced in postmortem brain of patients committing suicide, and that mice with genetic deletion of p11 have a depressive-like phenotype.
(26)
Small G proteins
In addition to the G-proteins associated with GPCRs, there is a super family of ‘small G-proteins’ which also bind GTP and possess intrinsic GTPase activity but these are not modulated by agonist binding. Rather, small G-proteins function as molecular switches that control several cellular processes ranging from vesicle trafﬁ  ck-

ing and exocytosis (e.g. Rab) to assembly of cytoskeletal structures (e.g. Rho). Among the best characterized small G-proteins are those that comprise the Ras family. Numerous types of cell signals including those of most neurotrophic factors converge on Ras and related proteins to regulate MAP-kinase pathways.
Second messengers
The generation of the second messengers cAMP and DAG by ade-nylate cyclase and phospholipase C, respectively, leads to activation of protein kinases that add phosphate groups to speciﬁ  c protein 
targets to change their activity and ultimately trigger diverse physi-ological responses (Fig. 2.3.4.2). Enzymes called phosphatases, 
Fig. 2.3.4.2 Diagrammatic representation of ligand-gated ion channel and G-protein coupled receptors. Ligand-gated

Fig. 2.3.4.2 Diagrammatic representation of ligand-gated ion channel and G-protein coupled receptors. Ligand-gated 
ion channels comprise multiple protein subunits that form a central pore in the plasma membrane. On binding of the neurotransmitter, this receptor mediates fast excitatory or inhibitory transmission depending on whether the pore gates cations or chloride ions, respectively. G-protein coupled receptors comprise a single membrane spanning protein. On binding 
of the neurotransmitter, this receptor mediates slow transmission by enabling the dissociation of the G-protein into α subunit 
monomer and β/γ subunit dimer, both of which may activate an effector enzyme to generate a second messenger. Also, the 
β/γ subunit dimer may directly interact with ion channels. Second messengers may also indirectly modulate ion channels

β/γ subunit dimer may directly interact with ion channels. Second messengers may also indirectly modulate ion channels 
through phosphorylation by activating protein kinases. Reproduced from Nestler EJ, Hyman SE and Malenka RC (2001) Molecular Neuropharmacology , p. 64, Copyright 2001, McGraw-Hill, New York.
Ligand-gated ion channel G protein-coupled receptor
TransmitterReceptor
ChannelTransmitter
Receptor
G proteinGDP
GTPPGate
Second
messenger
generating
enzyme
Second
messenger
Extracellular side
Cytoplasmic side1
2
3
CProtein
kinaseEffector
function Extracellular side
Cytoplasmic sideGate
N
C
ααα
α
δββ
β
γγ
γ2.3.4 neurotransmitters and signalling

SECTION 2  the scientific basis of psychiatric aetiology 176
which remove the phosphate groups, oppose these signalling 
effects. Guanylate cyclase is a cytosolic enzyme which also gener-ates a second messenger, cGMP . As noted above, guanylate cyclase is activated by NO to produce effects on presynaptic function.
Based on molecular cloning studies, nine forms of adenylate 
cyclase have been identiﬁ  ed (I–IX) and each exhibits a distinct 
distribution in brain and peripheral tissues.
(27) The full implica-
tion of this complexity is not yet understood but it suggests that regulation of cAMP formation varies depending on the form of adenylyl cyclase expressed in neuronal cells.
Both cAMP and cGMP are degraded by phosphodiesterases 
(PDEs) which are expressed in numerous forms (types 1–11) in brain and periperal tissues.
(10) At high concentrations, caffeine and

(10) At high concentrations, caffeine and 
related methylxanthines inhibit PDE and this action contributes to the pharmacological effects of these drugs. Much effort is being made to develop inhibitors that are selective for brain-speciﬁ  c 
forms of PDE. Rolipram inhibits all isoforms of PDE4; this drug showed promise as an antidepressant, but its clinical utility was limited by peripheral side effects. However, because the PDE4 enzymes comprise a number of isoforms, an inhibitor of one isoform may lead to the development of an effective antidepressant without the side effects of rolipram.
GPCR-induced activation of PLC causes the breakdown of phos-
phatidylinositol, resulting in the generation and recycling of the second messengers, IP
3 and DAG (phosphoinositide cycle). Both 
IP3 and DAG produce downstream signalling effects, IP3 through

IP3 and DAG produce downstream signalling effects, IP3 through 
the mobilization of intracellular calcium stores and DAG through activating a protein kinase. There are two major isoforms of PLC in brain, β and γ, the β isoform being predominantly responsible for 
mediating the effects of GPCRs linked to Gq.
After its formation, IP
3 is recycled via a series of dephosphory-
lations to form inositol which is used in the regeneration of phosphatidylinositol. Interestingly, lithium, which is an important drug in the treatment of manic depressive illness, inhibits one of the enyzymes involved in the recycling of IP
3 (inositol-1-mono-

phosphatase) and causes inositol depletion. Because inositol does not easily enter the blood-brain-barrier, brain inositol levels are thought to fall and production of the second messengers diminishes. It is a popular hypothesis that inositol depletion is responsible for lithium’s clinical effects but this remains unproven. Indeed, lithium is known to interact with a range of signalling systems including various ion channels, adenlyate cyclases and protein kinases. Recent interest has focussed on the inhibition by lithium and mood stabi-lizing anticonvulsants such as valproat e, of glycogen synthase kinase 
3β that has a range of targets and effects ranging from formation of 
inositol to trophic mechanisms.
(28)
Downstream signalling cascades

(28)
The activation or inhibition of second messenger signalling cascades by GPCRs can profoundly change the intracellular environment of a neurone by regulating the activity of protein kinases and other proteins, including gene transcription factors and even enzymes involved in regulation of chromatin structure. Consequently, these cascades may regulate gene transcription and protein synthesis and activate multiple downstream effectors, including those that form the cytoskeleton or contribute to mechanisms underlying synaptic plasticity. Such effects can have long-lasting effects on neuronal function. Increasing evidence suggests that the neuroadaptive responses to repeated psychotropic drug administration are under-
pinned by changes in gene expr ession that result in the remodelling of

pinned by changes in gene expr ession that result in the remodelling of 
synaptic function and structure. T his thinking has been applied to 
explain a range of processes incl uding compulsive recreational drug 
use as well as the therapeutic action of antipsychotic drugs.
As an example, the past decade has seen the evolution of a fasci-
nating theory to explain the delayed onset of antidepressant effect of drugs like ﬂ  uoxetine and imipramine that act to inhibit plasma 
membrane amine transporters (see above). This theory posits that elevated amine levels trigger GPCR signalling cascades that activate gene programmes to enhance neuronal survival and connectivity, the latter having failed because of the adverse effects of stress and other environmental factors.
(11, 29, 30) Some of the key genes

(11, 29, 30) Some of the key genes 
involved in this process include trophic factors such as BDNF, which may be a trigger for the production of newly formed neu-rones (Fig. 2.3.4.3). Although this line of thought is driving prom-ising pharmacological strategies for improved antidepressant therapies, our knowledge of the key molecules that are changed by antidepressants to bring about the relief of the symptoms of depression is far from complete.
Concluding remarks
Until recently, studies on the chemistry of synaptic neurotransmis-sion have focused on a small number of neurotransmitters and a narrow group of proteins involved in neurotransmitter function, 
Fig. 2.3.4.3 Hypothetical signal transduction pathways regulated by

Fig. 2.3.4.3 Hypothetical signal transduction pathways regulated by 
antidepressant drugs leading to increased neurotrophic factor expression and neurogenesis. Antidepressant treatment increases synaptic amine levels that stimulate GPCRs (Gs) linked to adenylyl cyclase (AC). The subsequent increase in cAMP levels activates cAMP-dependent protein kinase (PKA) which, possibly 
together with Ca
2+-dependent protein kinases, increases the function and 
expression of the gene transcription factor, cAMP response element binding protein (CREB). CREB enhances the expression of brain derived neurotrophic factor (BDNF) that may underpin trophic effects of antidepressant treatment, including 
synaptic remodeling and increased neurogenesis. Reprinted by permission from 
Macmillan Publishers Ltd: Molecular Psychiatry, DOI: 10.1038/sj/mp/4001016.Antidepressant Treatment
Inhibit 5-HT and NE
reuptake or breakdown
RRGs
PDE
InhibitorcAMP
PKA
CREB
BDNF Gene
ExpressionTrophic actions: altered

RRGs
PDE
PKA
CREB
BDNF Gene
neuronal plasticity and
cellular morphologyCa2+-dependent kinases
nucleusACGx

177
speciﬁ  cally neurotransmitter receptors, transporters and enzymes 
which bring about neurotransmitter synthesis or degradation. T oday, powerful molecular and genetic approaches are being used to identify and understand new proteins and mechanisms involved in neurotransmitter function and control. So far, just a few tens of perhaps thousands of neurotransmitter-related proteins, have been successfully targeted by pharmacological agents that have translated into important treatments of psychiatric disorder but there is promise of many more such treatments to come. Moreover, this huge diversity of neurotransmitter-related proteins is now emerg-ing as a large resource for studies of genetic risk factors of psychiat-ric disorder and investigations of biological markers of illness diagnosis and progression, and treatment outcome.
International Union of Basic and Clinical Pharmacology (IUPHAR) 
committee ofﬁ  cial database on receptor nomenclature and drug

committee ofﬁ  cial database on receptor nomenclature and drug 
classiﬁ  cation, http://www.iuphar-db.org/index.jsp.
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2.3.5 Neuropathology
The traditional domains of neuropathology are well-deﬁ  ned

The traditional domains of neuropathology are well-deﬁ  ned 
organic brain diseases with an obvious pathology, such as tumours, infections, vascular diseases, trauma, or toxic and hypox-emic changes, as well as degenerative brain diseases (e.g. Alzheimer’s disease, Parkinson’s disease, and Huntington’s cho-rea). Neuropathological investigations of these brain disorders have been rewarding, because patients with any of these condi-tions can be expected to have gross morphological or more or less speciﬁ  c neurohistological anomalies related to the clinical symp-
toms of the disorders. Moreover, the type of brain pathology of these well-deﬁ  ned disease entities is quite homogenous. For 
example, it is highly unlikely that a patient with Parkinson’s dis-ease would not exhibit morphological changes and Lewy bodies 2.3.4 neurotransmitters and signalling

SECTION 2  the scientific basis of psychiatric aetiology 178
in the nigrostriatal system, just as much a person with Huntington’s 
chorea would have a normal striatum, or a patient with Pick’sor Alzheimer’s disease would have no changes in the cerebralcortex.
In contrast, the history of the neuropathology of psychiatric 
disorders outside primary degenerative diseases is much more controversial, because no such obvious and homogenous types of brain pathology (as seen in neurological disorders) have yet been detected for the major psychiatric illnesses such as schizophrenia, affective disorders, substance-related disorders, or personality disorders.
The scope of this chapter is to summarize the neuropathological 
ﬁ ndings in schizophrenia, affective disorders, and alcoholism. 
Tables 2.3.5.1, 2.3.5.2, 2.3.5.3, and 2.3.5.4 highlight the signiﬁ  cant 
ﬁ ndings. It goes beyond the scope of this chapter to review the

large body of literature on the dementias, including specifi-cally Alzheimer’s disease. Concerning this matter, the reader is referred to several comprehensive reviews (e.g. Jellinger and Bancher 1998).
(1)Schizophrenia and other psychotic disorders
Studies between 1898 and 1975
In 1898, Alois Alzheimer (1898)(2) described subtle changes in the 
neocortex of patients with schizophrenia. Subsequently to Alzheimer, Southard reported cortical atrophy in schizophrenia and mentioned association areas of the cerebral cortex to be most affected in this disorder.
(4) Vogt and Vogt and their coworkers 
reported cellular alterations in the cortex, thalamus, and basal gan-glia of schizophrenics.
(5) These considerable efforts on the part of

(5) These considerable efforts on the part of 
many well-known neuroanatomists and neuro pathologists to prove schizophrenia to be a primary brain disorder ended in inconsistent and unsubstantiated ﬁ  ndings.
(6) T o a large extent, these inconsist-
encies can be attributed to a variety of methodological inadequa-cies including diagnostic uncertainties, inadequate control samples, ﬂ awed tissue-handling procedures, variable choice of brain regions 
for neuropathological studies, limitations in the sensitivity and speciﬁ  city of classical histological stains, as well as lack of quantita-
tive methods to delineate and analyse subtle brain abnormalities.
(7)
Table 2.3.5.1  Gross morphometric ﬁ  ndings in schizophrenia
Region/parameter Finding
General
Brain length (↓)
Brain weight ↓
Ventricular area/volume ↑
Cortex thickness ↓
Temporal lobe

(7)
General
Lobar area/volume ⎯
Hippocampal area/volume ↓
Parahippocampal area/volume ↓
Parahippocampal cortical thickness ↓
Amygdala area/volume ⎯
Sylvian ﬁ  ssure length, planum temporal volume ↓
Sulcogyral pattern Abnormal
Frontal, parietal, and occipital lobes
Cingulate cortical thickness ⎯
Insula area/volume ⎯
Corpus callosum thickness (↑)
Internal capsula area/volume ⎯
Basal ganglia
Globus pallidum area/volume (↓)
Nucleus accumbens area/volume ↓
Cautdate-putamen area/volume ↑
Thalamus
Mediodorsal nucleus area/volume (↓)
Whole and various nuclei area/volume ⎯
Cerebellum
Anterior vermis area ↓
Brainstem
Substantia nigra volume ↓
Locus coeruleus volume ⎯
Periventricular grey volume ↓
In comparison with controls: ↓, reduced; ↑, increased; —, no difference; ( ), ﬁ  nding not or 
only partially replicated.

Adapted from Arnold and Trojanowski.(3)Table 2.3.5.2 Neuronal morphometric ﬁ  ndings in schizophrenia
Superior temporal gyrus (Tpt) neurone density ↓
Hippocampal neurone density (↓)
Hippocampal neurone size (↓)
Entorhinal cortex neurone density (↓)
Entorhinal cortex neurone size ↓
Amygdala neurone density (basolateral n.) ⎯
Frontal lobe
Prefrontal cortex pyramidal neurone density ↑
Prefrontal cortex interneurone density (↓)
Prefrontal cortex neurone size ↓
Cingulate (anterior) pyramidal neurone density ↓
Cingulate interneurone density ↓
Cingulate neurone size ↓
Motor cortex neurone density (↓)
Motor cortex neurone size ⎯
Globus pallidus neurone counts ⎯
Nucleus accumbens neurone counts ↓
Nucleus basalis of Meynert neurone counts ⎯
Thalamus

Thalamus
Mediodorsal nucleus neurone counts (↓)
Purkinje cell density ↓
Brainstem
Substantia nigra neurone density ↓
Substantia nigra neurone size ⎯
Locus coeruleus neurone densityLocus coeruleus neurone sizePedunculopontine nucleus neurone density ↓
Adapted from Arnold and Trojanowski.(3)

179
Neuropathological ﬁ  ndings in schizophrenia 
since 1975
Advances in the last 30 years have produced more reliable psychiatric 
diagnostic criteria, improved structural and functional neuroimag-ing techniques, a large array of highly sensitive and speciﬁ  c molecular
probes and labeling procedures, suitable for use in neuropathologicalstudies, and computer-assisted image analysis methodologies. For these and other reasons, there has been a resurgence of interest in the neurobiological substrates of schizophrenia, and contemporary neuropathological studies have enumerated many findings in the brains of patients with schizophrenia (for reviews see
(7, 8, 9) ). 
Finally, the recent description of the first risk genes like Neuregulin-1 or Dysbindin has provided this ﬁ  eld with reliable 
research targets.
(8, 9) T o identify the role of these genes for the 
pathophysiology of schizophrenia their expression pattern in human brain tissue has to be established in the near future.

(a) Diagnostic neuropathology
Stevens (1982)(10) surveyed the brains of 28 schizophrenic patients 
for gross and microscopic abnormalities using standard diagnostic stains. She discovered no abnormalities in temporal (including the amygdalohippocampal region), frontal, or parietal lobes or in the thalamus, but detected assorted abnormalities in other regions, including neuronal loss or infarction in the globus pallidus in ﬁ  ve 
patients, increased cerebellar white matter gliosis in ﬁ  ve patients, 
excessive Purkinje cell loss in 13 cases, and, most notably, increased ﬁ brillary gliosis in periventricular, periaqueductal, and basal fore-
brain regions bilaterally.
In another prospectively accrued series,
(10) she found that of

(10) she found that of 
56 schizophrenics ﬁ  ve were afﬂ  icted with other distinct neurologi-
cal illnesses (multiple sclerosis, Friedreich’s ataxia, epilepsy, stroke) and three had been treated with prefrontal leukotomies. The remaining 48 showed no differences to controls in the frequency of large- or small-vessel cerebrovascular disease, senile plaques, or neuroﬁ  brillary degeneration. However, there was an ‘increased 
incidence of unexpected pathology in the schizophrenic group compared with the control group’ . Of these 48 schizophrenics, 21 exhibited some degree of focal pathology compared to 12 of 56 controls, but these abnormalities were diverse in nature and 
location. Holzer staining suggested a signiﬁ  cant increase in ﬁ  brous

location. Holzer staining suggested a signiﬁ  cant increase in ﬁ  brous 
gliosis in the cortex, white matter, and periventricular structures, but generally for those brains showing other focal pathology. After removal of these cases, the ‘adjusted’ group showed no evidence of increased gliosis.
In a series of 101 elderly schizophrenics,
(12) Golier et al . found 
only 10 with deﬁ  nite or probable Alzheimer’s disease by modern 
neuropathological diagnostic criteria, 29 with senile plaques, 15 with vascular lesions, two with Parkinson’s disease, three with unspeciﬁ  ed tumour, and ﬁ  ve with ‘other’ ﬁ  ndings.
Another review concluded extensive neuropathological investi-
gations due to lack of any evidence of neurodegeneration or neural injury beyond what typically is observed in brains of individuals without neuropsychiatric illness.
(8)
(b) Morphometric studies
Macroscopic ﬁ  ndings (Table 2.3.5.1)

(8)
Several planimetric postmortem studies of the entire cortex have been performed, some reporting signiﬁ  cant reduction of cortical 
volume (12 per cent) and central grey matter (6 per cent), and others reporting no difference in volumes of cortex, white matter and whole hemispheres between schizophrenics and controls. Others that measured general brain parameters have shown reduced brain length, brain weight, and increased ventricular area/volume.
Since the publication of the ﬁ  rst report of reduced tissue volume 
in temporolimbic structures of schizophrenics,
(13, 14) numerous

(13, 14) numerous 
quantitative or qualitative anatomical postmortem studies on limbic structures of schizophrenics have been conducted. The majority of these studies substantiated subtle structural changes (15–20 per cent mean volume reduction) in at least one of the inves-tigated areas, whereas only a few yielded entirely negative results. The ﬁ  ndings comprise reduced volumes or cross-sectional areas of 
the hippocampus, amygdala, parahippocampal gyrus, which were later corroborated by morphometric magnetic resonance imaging (MRI) studies. Figure 2.3.5.1 demonstrates the subtle bilateral vol-ume reduction of the hippocampus in schizophrenics and further-more visualizes the kind of hypoplastic appearance of the anterior hippocampus, which can be seen in about one third of the patients 2.3.5 neuropathology

Fig. 2.3.5.1 Left side: hippocampal volumes in schizophrenic patients and co ntrols; Right side: lippocampal atrophy macroscopically seen in about one-third of patients 
with schizophrenia (upper row) compared to control subjects (lower row) (from Bogerts 1990).

SECTION 2  the scientific basis of psychiatric aetiology 180
(lower row of the photographs). Other ﬁ  ndings in limbic brain 
regions are left temporal horn enlargement, white-matter reduc-tions in parahippocampal gyrus or hippocampus, and an increased incidence of a cavum septi pellucidi.
Unchanged volumes of the striatum and external pallidum but a 
subtle volume decrease in the internal pallidal segment were found in brains from the preneuroleptic era. Pallidal volume reduction was due to a reduction in the catatonic subgroup.
(15) These initial 
ﬁ ndings have to be pursued, as longitudinal MRI studies suggest 
that enlargement of basal ganglia can be seen in schizophrenia as a consequence of treatment with classical neuroleptics, which can be reversed by the use of atypical substances.
(16)
After initially ﬁ  nding no volumetric changes in the thalamic 
nuclei, subsequently the area/volume of the mediodorsal nucleus and anteroventral thalamic nucleus were found to be decreased.

(16)
(17)
Changes in area measurements of the corpus callosum were 
described in some studies. The ﬁ  ndings, however, are inconsistent; 
there are reports of increased as well as of decreased midline areas. More consistent are reports of shape abnormalities, in that the sex difference in anterior and posterior callosal thickness in normal con-trols seems to be reversed in schizophrenics and the mean curvature in the corpus callosum is bent upwards.
(18)
Findings of decreased volume of the substantia nigra and the 
periventricular grey matter as well as no volumetric change in the locus coeruleus await replication.
Microscopic ﬁ  ndings (Table 2.3.5.2)

There are a number of studies of neurone number, density, and size in schizophrenia. As summarized in Table 2.3.5.2, the majority of these have focused on the ventromedial temporal and frontal lobes.
In the lateral prefrontal cortex, an increase in neurone density has 
been reported inconsistently, which may relate to the observed decrease in neurone size (with decreased dendritic arborization and a decreased neuropil compartment).
(20) In the anterior cingulate 
could be observed decreased pyramidal and local circuit neurone density accompanied by increased vertical axon density and altered dopaminergic innervation. These ﬁ  ndings have been interpreted as 
representing disturbed connections in the anterior cingulate.
Within the ventromedial temporal lobe, reduced cell numbers or

Within the ventromedial temporal lobe, reduced cell numbers or 
cell size and abnormal cell arrangements in the hippocampus or entorhinal cortex were described. However, some groups could not conﬁ  rm cellular disarray in the hippocampus
(21) just as little ﬁ  nd 
signiﬁ  cant volume and cell number reductions in the hippocam-
pus and entorhinal cortex.(22)
Original studies demonstrating decreased neuronal counts in 
the mediodorsal and anteriorventral nucleus of the thalamus have been partially supported by subsequent investigations.
(17)
The lateral (nigrostriatal) and medial (mesolimbic) parts of the 
mesencephalic dopaminergic systems have been evaluated and the size of the nerve cell bodies found to be signiﬁ  cantly reduced

(17)
mesencephalic dopaminergic systems have been evaluated and the size of the nerve cell bodies found to be signiﬁ  cantly reduced 
in the medial part by 16 per cent, while the cell numbers were unchanged. The reduced cell size of the medial, mesolimbic neurones were taken to indicate dopaminergic underactivity. Two qualitative reports on degenerative changes in cholinergic cells in the basal nucleus of Meynert of schizophrenics have been pub-lished; more recent quantitative studies found normal cell numbers in the basal nucleus of schizophrenics. Volume measurements and cell counts in the noradrenergic locus coeruleus revealed a trend for decreased locus coeruleus volume without loss of neurones, 
indicat ing a reduction of neuropil in schizophrenics. These results

indicat ing a reduction of neuropil in schizophrenics. These results 
appear comparable to those described in the substantia nigra, as mentioned above. Investigating the brainstem reticular formation revealed a twofold increased number of the cholinergic neurones of the pedunculopontine nucleus and the dorsal tegmental nucleus as well as a reduced cell size in the locus coeruleus.
(23,24)  However, 
these results are not undisputed as newer studies using state of the art stereology demonstrate opposite ﬁ  ndings.
(25)
Schizophrenia as a disorder of brain maturation
There is evidence from clinical research implicating aberrant 
neurodevelopmental processes in the pathophysiology of schizo-phrenia,
(26) but there is also a growing literature suggestive of pro-
gressive deterioration in the disease for a substantial proportion of patients.
(27) It should be noted that abnormal neurodevelopmental

(27) It should be noted that abnormal neurodevelopmental 
processes are not mutually exclusive of neurodegenerative mecha-nisms in the pathogenesis of complex neuropsychiatric disorders. Indeed, while some genetic disorders are mainly developmental (e.g. fragile X syndrome) and others mainly neurodegenerative (e.g. Huntington’s disease), some have both developmental and degenerative pathologies (e.g. Down syndrome). Based on the neuropathological literature of the last 30 years some suggestions can be made concerning the pathophysiology of schizophrenia.
(c) Gliosis

Glial cells, mainly astrocytes (Figs. 2.3.5.2 and 2.3.5.3), show changes in response to almost every type of injury or disease in the central nervous system. Therefore, in typical degenerative brain disorders such as Alzheimer’s disease or Huntington’s chorea increased glial cell densities are found. Most studies using glial cell counts, neuron-to-glial ratios and glial cell nuclear volumes found no difference between schizophrenics and controls in temporolimbic structures, the thalamus, and cingulate co rtex. In our own larg e-scale
study we counted the number of astrocytes in several key regions such as the area surrounding the temporal horn and found no evi-dence for astrogliosis in schizophrenia (Fig. 2.3.5.3).
(28) Although 
the question of ﬁ  brous gliosis (i.e. increase in glial cell ﬁ  bres) 
remains more controversial, the well-controlled study by Bruton et al . (1990)
(11) also rejects fibrous gliosis in schizophrenia.

(11) also rejects fibrous gliosis in schizophrenia. 
Fig. 2.3.5.2 Macroglia in a control subject: Glial ﬁ  brillary acid protein (GFAP) 
positive astrocyte in the human cortex.

181
Therefore, it seems unlikely that the majority of schizophrenic 
patients show a considerable degree of astrogliosis. There is, on the contrary, some evidence demonstrating reduced macroglial densi-ties in major depression and schizophrenia.
(29) In this respect, spe-
ciﬁ cally the oligodendroglia demonstrates qualitative and quanti-
tative changes in schizophrenia(30) which is an interesting view of 
the riskgene Neuregulin-1 regulating myelin thickness via these cells. Some recent studies found evidence for the activation of microglia in the cortex of patients with schizophrenia.
(31, 32, 33) As 
microglia respond to neuronal injury within 24 to 48 hours, studies are needed to link psychopathology with these markers. The exam-ination of apoptic processes constitutes another interesting line of research supporting atypical degeneration with schizophrenia. Some recent studies demonstrate low-grade apoptotic processes in circumscribed brain regions in schizophrenia

(34, 35)  which is in line 
with other degenerative disorders showing similar features.(36)
(d)  Neurohistological indications of disturbed brain 
development
Subtle cytoarchitectural anomalies were described in the hippoc-
ampal formation, frontal cortex, cingulate gyrus, and entorhinal cortex in patients suffering from schizophrenia compared with control subjects. For example, signiﬁ  cant cellular disarray in the 
CA3-CA4 interface was described in the left and replicated in the right hippocampus.
(37) This was interpreted as a bilateral migra-
tional abnormality and broadly correlated with the degree of disease severity. One subsequent study was not able to fully repli-cate these ﬁ  ndings, but did conﬁ  rm a within-case correlation with 
severity; whereas another examination did not ﬁ  nd any signiﬁ  cant 
disarray distinguishing schizophrenics from controls. Another prominent ﬁ  nding was of an abnormal sulcogyral pattern or abnor-

mal gross conﬁ  guration of the temporal lobe and cytoarchitectonic 
abnormalities of the rostral entorhinal region as well as of the ventral insular cortex of schizophrenics.
(38, 39)  The cytoarchitec-
tonic abnormalities of the rostral entorhinal region consisted of heterotopic pre- α-cells in the pre- β-layer (layer III), which would 
normally belong to the pre- α-layer (layer II). This observation 
stimulated considerable research, with some studies supporting these ﬁ  ndings,
(40, 41) while others did not.(42)
In conclusion, cytoarchitectonic abnormalities recently described

In conclusion, cytoarchitectonic abnormalities recently described 
in different limbic structures in schizophrenia are very subtle and can easily be missed using classical neuropathological methods. Quantifying them often needs sophisticated staining methods, for example, immunohistochemistry, serial sections and a matched control group and even then replicating original ﬁ  ndings seems difﬁ cult, as outlined above. These ﬁ  ndings can be interpreted as 
a sign for disturbed late neuronal migration or could mirror dis-turbed programmed cell death as heterotopias are frequently found in the temporal cortex of autopsied children, which seem to disappear in adults.
(e) Summary and pathophysiological conclusions

There is growing evidence for pathomorphological abnormalities in the postmortem brains of patients suffering from schizophrenia. The changes are focused on the frontal lobe and temporolimbic regions. They are subtle, lacking the typical signs of degeneration, and point to problems in prenatal (cell migration) and postnatal (connectivity) periods of brain development. Currently, underly-ing causes remain ambiguous, but the interaction between genetic and non-genetic factors (e.g. birth complications) is presently dis-cussed on the basis of the recently found risk genes like Neuregulin-1 or Dysbindin.
Mood disorders (Table 2.3.5.3)
The number of published pathoanatomical studies in schizophre-nia contrasts with the scant number of neuropathological exami-nations in affective disorders. In reviewing the world literature up to 1988, Jeste et al. (1988)
(43)counted 15 neuropathological studies

(43)counted 15 neuropathological studies 
on affective disorders. Seven of them were published between 1949 and 1969, attended to less than four cases, and utilized qualitative tissue evaluation. Searching for ‘unipolar depression and neuropa-thology’ and ‘bipolar depression’ , resulted in 56 and 77 hits in pubmed up to 2007, proving this ﬁ  eld of research to speed up lately. 
Comprehensive reviews
(44, 45, 46) highlight several aspects in more 
detail and are suggested for further reading. Table 2.3.5.3 summa-rizes the most relevant ﬁ  ndings from morphometric post-mortem 
studies.
Macroscopic ﬁ  ndings
Four studies examined macroscopic measures such as the gross 
brain morphology,(47) brain weight and ventricular volume,(48)
and the area or volume of speciﬁ  c regions such as the hippocam-
pus, parahippocampal gyrus (Altshuler et al . 1990), striatum, 
globus pallidus, and corpus callosum.(48, 49)  In comparison to

globus pallidus, and corpus callosum.(48, 49)  In comparison to 
schizophrenic patients and/or non-psychiatric control subjects, patients with affective disorders revealed caudate lesions,
(47)
reduced area of the right parahippocampal gyrus,(50) increased 
brain and reduced ventricular volume.(48)
Microscopic ﬁ  ndings
Several studies examined the cytoarchitecture and nerve cell, 
interneuronal or glial numbers of the pre- and orbitofrontalcortex,
(51, 52, 53)  entorhinal and insular cortex,(54, 55)  anterior cingu-
lated(56, 57) cerebellum,(58) brainstem(49, 59) and the peripheral 
nervous system.(60) Findings in patients with affective disorders

nervous system.(60) Findings in patients with affective disorders 
included overall reduced neuronal numbers, together with disurbed cytoarchitecture of entorhinal cortex, reduced neuronal and glial numbers in the prefrontal cortex, the rostroventral insula and dor-sal raphe, reduced Purkinje cells in anterior and posterior vermis and hemispheres of the cerebellum, reduced interneuronal num-bers in layer II of the cingulate, but increased neuronal numbers of the locus coeruleus and peripheral motor neurone branching. In a series of studies focusing on the hypothalamus in affective disor-ders, the number of nitric o xide synthase (NOS) positive cells was 2.3.5 neuropathology
Fig. 2.3.5.3 No signiﬁ  cant increase of GFAP positive cells around the left 
temporal horn in schizophrenia.

SECTION 2  the scientific basis of psychiatric aetiology 182
reduced in the nucleus suprachiasmaticus(61)and the paraventricu-
lar nucleus(62) in patients with affective dis order stressing the 
importance of this anatomical region for these illnesses.
Summary and pathophysiological conclusions
In summary, the number of postmortem studies on mood disor-ders is still limited but growing. There is some evidence for changes in key cortical regions, the basalganglia, the hypothalamus and brainstem. Structural brain imaging studies support the notion of mood disorders being associated with regional structural brain abnormalities, in particular regions involved in mood regulation. Because small numbers of subjects were studied, only some post-mortem studies distinguished between unipolar and bipolar depression.
(49) Nevertheless, recent structural imaging studies

(49) Nevertheless, recent structural imaging studies 
regarded this distinction worthwhile. The main abnormalities found in unipolar depression are smaller basal ganglia, cerebellum, frontal lobe and hippocampus, which may reflect disease-course-related atrophy. Bipolar disorder appears to be associated with larger third ventricle, smaller cerebellum, possibly smaller temporal lobe, and perhaps increased amygdala volume on the right side. In both groups, there seems to be an increased rate of subcortical white-matter lesions and periventricular hyperintensit ies. 
Whether the rate of subcortical white-matter lesions and peri-ventricular hyperintensities are predictive of a later development of Alzheimer´s disease is yet unclear. Hippocampal plaques and tan-gles are increased in patients with Alzheimer´s disease with a life-time history of major depression.
(63) Further studies are needed, combining endocrine/biochemical parameters with structural

(63) Further studies are needed, combining endocrine/biochemical parameters with structural 
parameters to identify the key regions involved in processes central to mood disorders such as changes in the regulation of the hypothalamic-pituitary-adrenal axis.
Alcoholism (Table 2.3.5.4)
The best known neuropathological feature of alcoholism is Wernicke’s encephalopathy, which is characterized by degenerative changes including gliosis and small hemorrhages in structures surrounding the third ventricle and aqueduct (i.e. the mamillary bodies, hypotha-lamus, mediodorsal thalamic nucleus, colliculi, and midbrain teg-mentum), as well as cerebellar atrophy. Most of the clinical features associated with the Wernicke-Korsakoff syndrome including oph-thalmoplegia, nystagmus, ataxia, and mental symptoms such as con-fusion, disorientation, and even coma can be related to damaged functional systems in the hypothalamus, midbrain, and cerebel-lum.

(64) Other important neuropathological manifestations of 
chronic alcoholism are central pontine myelinolysis, Marchiafava syndrome, and foetal alcohol syndrome (see Chapter 4.2.2.3).
Studies on alcohol-speciﬁ  c brain damage
Most of the changes mentioned above occur in association with 
thiamin deﬁ  ciency, which is frequently, but not always, correlated 
with the long-term use of excessive amounts of alcohol. One major challenge is to identify those lesions caused by alcohol itself (uncomplicated alcoholism)
(65) and those caused by other common 
Table 2.3.5.3  Morphometric post-mortem studies in affective disorders
Study Number of patients/controls Region/parameter Finding
General
Jellinger (1977)(46)4/15 Entire brain Caudate lesions
Altshuler et al.  (1990)(49)12/27 Hippocampal area ⎯
Parahippocampal area ↓
Beckmann and Jakob (1991)(53)4/0 Cytoarchitecture of entorhinal cortex Disturbed
Rostroventral insula nerve cell number ↓

Casanova et al.  (1991)(54)5/10 Entorhinal cortex neuronal numbers ↓
Other cortical and subcortical regions
Brown et al.  (1986)(47) 70/32 Lobar structures ⎯
Callosal thickness ⎯
Corpus striatum ⎯
Brain weight ↑
Lateral ventricles ↓
Diekmann et al.  (1998)(55)12/12 Cingulate cortex (interneurones in layer II) ↓
Baumann et al.  (1999)(48) 8/8 Accumbens, putamen, caudate, external pallidal volumes ↓
Bernstein et al.  (1998)(62) NOS positive cells in the nucleus paraventricularis ↓
Bernstein et al.  (2002)(61)NOS positive cells in the nucleus suprachiasmaticus ↓
Lohr and Jeste (1986)(57) 12/23 Cerebellum: Purkinje cells in anterior and posterior vermis and 
hemispheres⎯
Brainstem
Hankoff and Peress (1981)(58)4/26 Brainstem ⎯

Brainstem
Baumann et al.  (1999)(48)12/12 Locus coeruleus neuronal number ↑
Peripheral nervous system
Ross-Stanton and Meltzer (1981)(60)Motor neurone branching (peripheral) ↑
In comparison with controls: ↓, reduced; ↑, increased; —, no difference; ( ), ﬁ  nding not or only partially replicated.

183
alcohol-related factors, principally thiamin deﬁ  ciency. The follow-
ing paragraph summarizes recent results in this ﬁ  eld, which has 
been reviewed in detail by others.(65, 66)  Brain shrinkage can be 
found in uncomplicated alcoholism, which can largely be accounted for by loss of white matter. Some of this damage appears to be reversible. However, alcohol-related neuronal loss has been docu-mented in speciﬁ  c regions of the cerebral cortex (superior frontal 
association cortex), hypothalamus (supraoptic and paraventricular nuclei), and cerebellum. The data are conﬂ  icting for the hippocam-
pus, amygdala, and locus coeruleus. No changes are found in the basal ganglia, nucleus basalis, or serotonergic raphe nuclei. Concerning the prefrontal lobe it is interesting to note that although alcohol related pathology affects both neuronal and glial cells, the effects on glia are more dramatic than on neurones.
(52) The cellular

(52) The cellular 
changes are more prominent and spread across cortical layers in alcohol dependent subjects compared to subjects with mood disorders.
(52) As pointed out above, many of the regions being 
normal in uncomplicated alcoholics are damaged in those with Wernicke-Korsakoff syndrome. Dendritic and synaptic changes have been documented in uncomplicated alcoholics, and these, together with receptor and transmitter changes, may explain functional changes and cognitive deﬁ  cits that precede the more 
severe structural neuronal changes.
Summary and pathophysiological considerations
In summary, there is neuropathological evidence showing that alcohol per se  causes damage to both grey and white matter. White-
matter damage is predominant and results in a reduction in brain volume. A component of the white-matter loss appears to be revers-ible in some cases, given a signiﬁ  cant period of abstinence. The

matter damage is predominant and results in a reduction in brain volume. A component of the white-matter loss appears to be revers-ible in some cases, given a signiﬁ  cant period of abstinence. The 
grey-matter damage appears to be regionally selective, but many areas of the brain appear to be resistant to damage.
Thiamin deﬁ  ciency accounts for a major component of the brain 
damage in alcoholics. Animal models suggest the distribution and extent of neuronal loss to be dependent on the duration of alcohol exposure, the magnitude and mode of exposure (ingestion, inhala-
tion, etc.), the genetic susceptibility of the species, and the strain of 
animals studied.
(65) It has been suggested that alcohol withdrawal 
may play a role in brain damage, evidenced by the fact that a number of workers have shown loss of granule cells in the dentate gyrus of the hippocampus continuing even after alcohol exposure stops.
(67) It was furthermore suggested that up-regulation of N-

methyl-d-aspartate receptors may lead to withdrawal seizures and enhanced susceptibility to excitotoxicity, which may explain the continuing damage described.
(68)
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General
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Ventricular volume ↑
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General
Hippocampal neuronal numbers (↓)
Amygdala neuronal numbers ↓
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Primary motor cortex, neuronal numbers (BA 4) ⎯
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Purkinje cell densities ↓
Brainstem
Locus coeruleus noradrenergic, neuronal numbers (↓)

Brainstem
Median and dorsal raphe nuclei, neuronal numbers ⎯
Other brain structures
Basal nucleus, neuronal structures ⎯

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721–6.2.3.6 Functional positron emission 
Positron emission tomography ( PET ) and single-photon emission 
tomography ( SPET ) are powerful tools for investigating the patho-

physiology of psychiatric illnesses and the action of psychotropic drugs. With these techniques monoaminergic, cholinergic, opioid and benzodiazepine receptors, regional cerebral blood ﬂ  ow, glucose 
and oxygen metabolism can be measured in the living brain (Table 2.3.6.1). Thus, neural function of direct relevance to neurochemical 
and anatomical theories of psychiatric illnesses can be sampled.
Methodology of PET and SPET(1)
In brief, PET and SPET comprise the following:
◆ The production and incorporation of a positron or gamma-
emitting radio-isotope into a molecule of biological interest to form a radiotracer administered to humans (Plate 3).
◆ The use of PET or SPET cameras to detect the emitted gamma

◆ The use of PET or SPET cameras to detect the emitted gamma 
radiation from the decaying radio-isotope and hence the 3D dis-tribution of the radiotracer, over minutes to hours, in living human brain (Plate 4).
◆ Quantiﬁ  cation of a physiological parameter of interest, such as 
number of available receptors or regional cerebral blood ﬂ  ow, 
from the mathematical modeling of the measured radio-activity in the brain over time (Plates 5 and 6).
Production of isotopes
Common PET radio-isotopes, produced by a cyclotron, are oxy-gen-15 (
(15)O), carbon-11 ((11)C), and ﬂ  uorine-18 ((18)F) (with 
half-lives of 2.03 min, 20.4 min, and 109.8 min respectively) whilst SPET radio-isotopes include technetium (
(99m) Tc) and iodine-123 
((123)I) (with half-lives of 6.02 h and 13.2 h respectively). With

((123)I) (with half-lives of 6.02 h and 13.2 h respectively). With 
appropriate radiochemistry, isotopes can be incorporated into speciﬁ  c molecules to make radiotracers. Following quality control 
procedures, to estimate speciﬁ  c activity and radiochemical purity, 
the radiotracer is injected intravenously into subjects lying in the PET camera (Plate 3). Importantly, the total mass of radiotracer injected is very small (typically less than 5 μg) and therefore the radiotracer has no pharmacological effect itself.
PET versus SPET

SPET radiotracers are less diverse than PET tracers. However, SPET is cheaper than PET and less technically demanding, making it more readily available in hospitals and research centres. PET radio-chemical procedures require in-house automated rapid synthetic chemistry facilities in dedicated hot cells, whereas SPET chemistry is more straight-forward and does not require such extensive facili-ties. For research and quantitation purposes, PET is far superior to SPET, although any widespread commercial/clinical application is 2.3.6 functional positron emission tomography in psychiatry

SECTION 2  the scientific basis of psychiatric aetiology 186
likely to be SPET based because of the technology restraints and 
costs associated with PET scanning.
Imaging of radiotracer, data collection, and 
analysis
PET utilizes the disintegration of positrons emitted from unstable 
nuclei such as(11)C (Plate 4). Emitted positrons travel a short distance 
in tissue before annihilation by collision with an electron.(1) On anni-
hilation, two high-energy gamma rays are generated with a separation angle of 180
º (Plate 4). Radiation detectors (e.g. bismuth germanate), 
180º apart and linked in electronic coincidence circuits, detect the 
resulting gamma radiation and therefore localize the source of radia-tion to a volume between any two detectors (Plate 3). By arranging rings of detectors around the subject’s head and using computer-based back-projection techniques, the distribution of radiotracer within tomographic slices of the brain can be obtained.
(1) SPET

(1) SPET 
radioisotopes, in contrast, decay by emitting a single gamma ray and therefore the radiation detectors are not linked in coincidence circuits. State-of-the-art PET and SPET cameras have transaxial spatial resolu-tions of the order of 4 to 5 mm and can detect subnanomolar concen-trations of receptors.
(1)
Positron-emitting isotopes can be incorporated into molecules 
associated with diverse biochemical processes in the brain. For exam-ple, the positron emitter
(11)C can be incorporated into a molecule 
WAY 100635, which selectively binds to 5-HT1A receptors, and injected intravenously in tracer amounts. Brain regions will show 
different proﬁ  les of radio-activity accumulation over time as the 
radiotracer binds in areas with a high density of 5-HT1A receptors 
(medial temporal cortex) whilst in regions with no or sparse recep-tors (cerebellum), it will be washed out (Plate 5). By this means, speciﬁ  c and non-speciﬁ  c binding can be distinguished. With an

appropriate model of the radiotracer’s history in tissue over time, a quantitative measurement of 5-HT
1A receptor number in tomo-
graphic slices of the human brain can be obtained.(1) With some 
radiotracers (e.g. [11C]diprenorphine to label opiate receptors) it may be necessary to undertake radial artery cannulation to obtain an ‘input function’
(1) that describes the time course of presentation of 
radiotracer to the brain (Plate 6), whereas others tracers can be mod-eled with a ‘pseudo’ input function from a reference region.
Technical and practical limitations of PET 
and SPET compared with other imaging modalities
PET and SPET excel in the measurement of neurochemical param-
eters in vivo  at very low (subnanomolar) concentration. Such sen-
sitivity cannot be matched by other in vivo  methods such as proton

sitivity cannot be matched by other in vivo  methods such as proton 
magnetic resonance spectroscopy (millimolar range). However, radiation dosimetry limits the number of scans that subjects may receive. Full quantitation can often be achieved with PET, unlike Table 2.3.6.1  Established and novel radiotracers for psychiatry
Radiotracer Application Comments
PET radiotracers
H215O Blood ﬂ  ow Used to map dysfunctional brain areas involved in psychiatric illnesses. Effectively replaced by 
functional MRI techniques such as BOLD.
18F-FDG Glucose metabolism Used for many resting state studies and nowadays to deﬁ  ne psychotropic drug effects.
11C -SCH 23390
11C -NNC 112Dopamine D1 receptor Receptor occupancy studies with neuroleptics. Reports of altered cortical D1 receptors in drug naive 
schizophrenics.

11C -Raclopride Dopamine D2 receptor Robust demonstration of no elevation of striatal D2 receptors in drug naive schizophrenics. Striatal 
D2 receptor occupancy studies with many neuroleptics. Frequently used to index dopamine release.
11C -FLB-457 Dopamine D2 receptor High afﬁ  nity ligand; enabling extrastriatal D2 populations to be measured. Studies in schizophrenia 
in progress. Binding may be sensitive to endogenous dopamine release.
18F-Fallypride Dopamine D2 receptor High afﬁ  nity ligand; enabling striatal and extrastriatal D2 populations to be measured. Binding may 
be sensitive to endogenous dopamine release.
18F-Fluorodopa Dopamine synthesis capacity Radiotracer predominantly imageable in basal ganglia, cortical signal weak. Consistent r eports of 
raised 18FDOPA in schizophrenia.

11C -Flumazenil Central benzodiazepine receptors Labels all subtypes of central receptor.
11C -MDL-100907 5-HT2A receptors Most suitable ligand for imaging 5-HT2 receptors.
11C -WAY 100635
11C -desmethyl WAY
11C – FCWAY
18F - MPPF5-HT1A receptors Reports of reduced 5-HT1A availability in depressive and anxiety disorders
11C- DA S B
11C -McN 56525-HT transporter Studies in depressive illness. Occupancy studies of SSRIs.
Used to examine effects of ecstasy
SPECT radiotracers
99mTcHMPAO Blood ﬂ  ow Many resting state and two scan activation studies in psychosis.
123I-Iodobenzamide Dopamine D2 receptors Occupancy and dopamine release studies in schizophrenia
123I-Epidepride Dopamine D2 receptors Striatal and Extrastriatal D2 receptors. Used to show ‘limbic selectivity’ of certain neurolep tics

123I-QNB Muscarinic acetycholine receptors
123I-CIT Dopamine and 5-HT reuptake sites Studies in depressive illness

187
SPET. However, for imaging blood ﬂ  ow change, or its correlates 
such as BOLD arterial spin labeling (ASL) and functional magnetic resonance imaging (fMRI), now offer the possibility of repeated measures (without radiation exposure) that far exceed that possible with PET- and SPET-based methods of ﬂ  ow mapping. Full quanti-
tation of blood ﬂ  ow is not yet readily achievable with functional 
MRI without injection of contrast agents. In contrast, MRI based ASL can achieve full quantiﬁ  cation. One disadvantage of functional 
MRI over PET, for some subjects, is the noisy claustrophobic environment of the scanner, but generally subjects and paradigms studied with PET ﬂ  ow mapping can be readily investigated with 
functional MRI (see Chapter 2.3.8), although all test materials in the vicinity of the scanner have to be non-magnetic.
Structural MRI scanning is often used in conjunction with PET

Structural MRI scanning is often used in conjunction with PET 
activation and ligand binding techniques. The high-resolution anatomical information contained in MRI images can be used to precisely deﬁ  ne areas of activation or radiotracer binding observed 
in PET studies from single subjects.
PET and SPET, and even functional MRI, have relatively poor 
temporal resolution (seconds) compared with electrophysiological methods such as EEG, event-related potentials, and magnetoen-cephalography (milliseconds), but these methods in turn suffer from poor spatial resolution. Attempts to integrate information from these different modalities are a major focus of methodological research in many imaging centres.
PET and SPET imaging strategies in 
These techniques (see Table 2.3.6.2) are used to either measure

These techniques (see Table 2.3.6.2) are used to either measure 
brain receptors and neurochemistry, or map functional brain activ-ity via the indices of regional blood ﬂ  ow and glucose utilization. Each approach attempts to deﬁ  ne trait and state abnormalities of 
psychiatric illnesses or the effect of psychotropic drug action.
Because of the technical complexities, it is important to bear in 
mind the following questions when judging experimental results.
◆ What assumptions are made about the behaviour of the radio-
tracer in vivo ?
◆ Has the radiotracer been well validated for the apparent physio-
logical parameter measured ?
◆ Does the mathematical model of the radiotracer’s behaviour give 
a good ﬁ  t to the raw data?
◆ Is the spatial resolution of the PET camera sufﬁ  cient for the 
regions measured?
◆ What is the test-test reliability for the PET radiotracer measure?

◆ How have the raw PET images been modiﬁ  ed/treated in the data 
analysis?
◆ How have regions of interest been deﬁ  ned?
◆ Is there a possibility of observer bias in the measurements made?
◆ What statistical techniques have been used, and are the statistical 
thresholds appropriate?
◆ Do the statistics reﬂ  ect ﬁ  xed or random effects and the multiple 
comparisons made?
Measuring brain receptors and neurochemisty
Many neurochemical hypotheses, generated by post-mortem and animal data, can be rigorously tested with PET and SPET in the living brain whilst avoiding many of the confounding variables inherent in in vitro  techniques. Many receptor systems can be

studied (Table 2.3.6.1). For receptor mapping, particular successes in this area are the range of tracers available to image select compo-nents of dopaminergic and serotoninergic neurotransmission. For example, with presently available radiotracers it is possible to measure Dopamine D
1, striatal D2, extrastriatal D2, Dopamine reuptake 
sites, index Dopamine synthesis and endogenous dopamine release. For the serotonin system, 5-HT
1A, 5-HT2A and 5-HT transporters 
can be readily measured. However, the rate of discovery of new radiotracers, suitable for use in humans, is relatively slow. Many 
conditions have to be satisﬁ  ed to produce a suitable radiotracer for 
human use including blood-brain barrier permeability, high speciﬁ  c binding, receptor selectivity, absence of radioactive metab-

olites in brain, and adequate modelling of tracer kinetics (Plate 6). Practically, the increasing use of PET neuroreceptor mapping in the pharmaceutical sector should lead to a greater range of tracer avail-ability due to the large chemical libraries within the industry.
Mapping brain activity by imaging blood ﬂ  ow and 
glucose metabolism
Regional cerebral blood ﬂ  ow and glucose metabolism are indica-
tors of regional neuronal synaptic activity.(2) Radiotracers for these 
processes, such as H2(15)O to index blood ﬂ  ow, are used to image 
brain activity in psychiatric illness. Glucose metabolic mapping using [
(18)F]deoxyglucose has some disadvantages over flow 
mapping. Radiation dosimetry limits for [(18)F]deoxyglucose and 
the long half-life of the tracer restrict repeated measurement in a subject over a short time-scale. In contrast,

(15)O-based methods 
allow, for example, 12 measurements of regional blood ﬂ  ow over 
a 3 h period in a single subject.Table 2.3.6.2  Summary of PET functional brain imaging approaches
Functional brain mapping:  rCBF or metabolism is measured as an index of local 
neural activity
(a)  Studies in normal volunteers in which ‘activation’ paradigms are used to 
identify functional anatomy that is relevant to psychiatric disorders
(b)  Activation studies in patients who are compared with matched control 
subjects
(c)  Studies in which the biological variable (e.g. rCBF) is correlated with a 
relevant clinical variable (e.g. hallucinations) within the patient group
(d)  The longitudinal comparison of patients before and after various 
treatments and into clinical recovery

(e)  Cross-sectional studies of resting-state brain activity in patient groups in 
comparison with appropriate controls
Radioligand imaging : the speciﬁ  c uptake and binding of radiolabelled tracer 
compounds is measured
(a)  To estimate baseline radioligand uptake at rest in patient groups in 
comparison with controls
(b)  Within-patient group correlations between radioligand uptake and 
particular symptoms/signs
(c)  Longitudinal comparison of radioligand uptake in patients before and after 
various treatments and into clinical recovery
(d)  ‘Displacement’ or radioligand activation studies designed to detect 
changes in the levels of intrasynapcic neurotransmitters in response to a pharmacological or cognitive challenge
(e)  Investigation of the receptor binding and occupancy characteristics of

(e)  Investigation of the receptor binding and occupancy characteristics of 
psychotropic drugs
rCBF, regional cerebral blood ﬂ  ow.2.3.6 functional positron emission tomography in psychiatry

SECTION 2  the scientific basis of psychiatric aetiology 188
The rapid development of PET cameras and automated data 
analysis techniques in the last few decades has established ﬂ  ow-
based functional imaging as a large and active research activity.(2)
As the techniques of regional cerebral blood ﬂ  ow mapping have 
advanced there has been an equivalent sophistication of experi-mental design with rest state studies being overshadowed by activa-tion paradigms.
(2) In an activation design, subjects are engaged in 
a speciﬁ  c cognitive task whilst being scanned, for instance generat-
ing words, and the blood ﬂ  ow pattern is compared with ﬂ  ow pres-
ent in a baseline condition such as repeating words. PET activation experiments may involve categorical, correlational, and factorial designs.
(2) Although, the more recent advent of fMRI-

based methods is now surpassing PET-based methods for functional brain activation mapping, there are certain situations where PET-based methods may be preferred. These include functional mea-surements in brain areas prone to susceptabilty artifacts in fMRI such as the temporal poles/basal frontal areas. In addition, PET [
(18)F]deoxyglucose remains a more direct measure of neural 
activation than all ﬂ  ow-related methods including fMRI and ASL, 
a potentially important consideration when investigating the central functional effects of CNS drugs that might also alter blood ﬂ ow directly.
Novel designs and data analysis for PET studies
Developments in this area have been very rapid.(2) Examples would

Developments in this area have been very rapid.(2) Examples would 
include the use of principal components technique to analyze PET activation data sets and attempts to determine measures of func-tional and effective connectivity between brain regions activated by a given task. For PET receptor studies, the use of cluster analysis, parametric approaches and simpliﬁ  ed reference region models 
are of considerable interest and are now in common use.
(3)
Furthermore, attempts are being made to relate PET neurochemi-cal measures to other imaging modalities and genetic factors. Examples of studies in these areas would include explorations of the relationship between densities of 5-HT
1A receptors and amy-
gdala reactivity during emotional processing,(4) and inﬂ  uence of 
genetic polymorphisms on 5-HT1A receptor expression.(5)
Imaging pathophysiology: examples from 
schizophrenia research
Imaging dopamine receptors

Much research effort has focused on in vivo  PET/SPET measure-
ment of striatal dopamine D2-receptor number in schizophrenia 
following the initial post-mortem reports of increased striatal dopamine receptor number. Initially, using [
(11)C]N-methyl-
spiperone as a radiotracer, a two- to threefold raised striatal D
2-receptor number in drug-naive schizophrenics was reported.(6)
However, subsequently other investigators using [(11)C]raclopride, 
[(11)C]N-methylspiperone, [(123)I]iodobenzamide, [(76)Br]bromo-
lisuride failed to detect such elevations of striatal dopamine D2-
receptor number.(7,8) The different radiotracer methodologies 
used, the selectivity of radiotracers for dopamine D2, D3, and D4

receptor subtypes, and the clinical characteristics of the patients studied have been advanced as possible explanations for the failure to replicate raised striatal dopamine D
2-receptor number. However, 
given these conﬂ  icting but essentially negative results, attention 
has shifted in recent years to reports of increased presynaptic dopaminergic function measured with [(18)F]dopa(9) and cortical 
dopamine D1 receptors measured with [(11)C]SCH 23390 and 
[(11)C]NNC 112(10) in schizophrenia. Most recently low density 
extrastriatal D2 receptors are being imaged with [(11)C]FLB-457 
and [(18)F]Fallypride. However, the newer patient studies reporting 
changes of cortical D1 and extrastriatal D2 receptors await further 
replication.

A novel extension to studies utilizing PET/SPET radiotracers for 
imaging dopamine D2 receptors has been to index dopamine release 
during a pharmacological challenge in schizophrenia. Theoretically, PET/SPET has the potential to detect neurotransmitter release asso-ciated with behavioural and pharmacological challenges if sufﬁ  cient 
endogenous neurotransmitter is released to cause appreciable change (via receptor occupancy) in the number of ‘available’ receptors that can be ‘seen’ by a radioligand. For example, pre-dosing animals and human subjects with d-amphetamine, which releases dopamine, results in decreased [
(11)C]raclopride and [(123)I]iodobenzamide
binding to dopamine D2 receptors.(11) Enhanced release of striatal

binding to dopamine D2 receptors.(11) Enhanced release of striatal 
dopamine in acutely symptomatic patients with schizophrenia following pharmacological challenge has been reported in a large cohort.
(10, 12) In these studies, the displacement of radiotracer (pre-
sumably reﬂ  ecting increased release of dopamine) correlated with 
worsening of positive symptoms. This important ﬁ  nding of increased 
dopaminergic responsivity, together with the consistent reports of raised [
(18)F] FDOPA uptake, provide some of the most convincing 
in vivo  evidence to support the hypothesis of subcortical dopamine 
overactivity in schizophrenia.
Imaging blood ﬂ  ow change, hypofrontality and 
cortical inefﬁ  ciency
From the outset of the functional neuroimaging of schizophrenia 
there has been discussion as to whether the frontal lobes of patients are ‘less active’ than those of normal subjects.
(13) However, hypo-

frontality, whether at rest or during cognitive challenge, has not been a universal ﬁ  nding in all studies, making it a somewhat unre-
liable trait marker of schizophrenia. It has been found in about 50 per cent of resting-state studies but more often in activation paradigms.
(14) Discrepant results might be attributable to the 
nature and demands of the task used, task performance, and the symptom proﬁ  les of patients studied. For example, Frith et al.
(15)
and Fletcher et al. used PET to study paced verbal ﬂ  uency activa-
tions in chronic and acute schizophrenic patients, on and off neu-roleptic medication, respectively, and failed to ﬁ  nd hypofrontality.

tions in chronic and acute schizophrenic patients, on and off neu-roleptic medication, respectively, and failed to ﬁ  nd hypofrontality. 
But pacing tasks could be criticized on the grounds that slowing the task so that patients and normal subjects perform equally, fails to address a dysfunction that may be expressed when patients are required to produce ‘normal’ levels of performance. This is a difﬁ  -
cult issue to resolve. Pacing patients and controls means that per-formance levels may be matched, and therefore differences of brain activation are not confounded by the patients’ failure to do the task. Y et it may be instructive to image patients attempting to perform a task that stresses (dysfunctional) cognitive processes, produces altered brain activity and hence impaired performance.
Many authors have suggested hypofrontality may be most pro-

nounced in schizophrenic patients who have predominantly ‘negative’ symptoms. This view has received support from a large cross-sectional study of chronically symptomatic patients where resting blood ﬂ  ow was measured in 30 patients.
(16) Within this

189
group of schizophrenic patients, greater hypofrontality was seen 
among those with the most pronounced negative symptoms as assessed by factor analysis. That symptoms and not the diagnosis of schizophrenia per se  may be an important factor in hypofron-
tality is apparent in one study where poverty of speech (a sign of psychomotor retardation or poverty) was associated with reduced regional cerebral blood ﬂ  ow in the left dorsolateral prefrontal cor-
tex, irrespective of diagnosis of depression or schizophrenia.
(17)
Some SPET and PET studies also suggest a relationship between hypofrontality and the presence of positive symptoms,
(18, 19) and 
hypofrontality (at rest or on activation) may resolve when symp-toms improve.
(20) Finally, contrary to the earlier notions of hypo-
frontality an alternative view of ‘cortical inefﬁ  ciency’ has been

frontality an alternative view of ‘cortical inefﬁ  ciency’ has been 
advocated whereby patients with schizophrenia are suggested to have over activation (i.e. hyperfrontality) of frontal areas. In these studies it has been suggested that when patients and controls are performing at similar levels, patients show enhanced cortical acti-vation reﬂ  ecting the inefﬁ  cient signal processing within the fron-
tal cortex.
(21)
depressive disorders
Imaging 5-hydroxytryptamine receptors
Impressive progress has seen the development of new radiotracers 
for the 5-hydroxytryptamine ( 5-HT ) system; hypothesized to be 
dysfunctional in affective illness and to be the prime target for many antidepressant treatments. In particular, radioligands for 5-HT
1A,5-HT2A receptors, and the 5-HT transporter, are now 
established (Table 2.3.6.1).
One notable success is the radioligand [(11)C]WAY 100635 for

One notable success is the radioligand [(11)C]WAY 100635 for 
imaging 5-HT1A receptors in the human brain.(22) As many antide-
pressant treatments alter 5-HT1A receptor function in rodents, and 
5-HT1A knock out mice are anxious this ligand is proving useful 
investigating 5-HT1A receptor populations in depressed or anxious 
patients before and after treatment. Studies in anxiety and depres-sion are now being reported with suggestions of reductions of 5-HT
1A availability in these conditions.(23)
[(11)C]N-methylspiperone, [(18)F]altanserin, [(18)F]ethyl-
spiperone, [(18)F]setoperone or [(18)F]altanserin, and the SPET 
tracer [(123)I]ketanserin have been used to measure 5-HT2 receptor 
number; a receptor implicated in depressive illness, suicidal behav-iour, and psychosis. Many of these 5-HT
2 ligands have been ham-
pered by either the lack of selectivity, or the relatively low ratio of

pered by either the lack of selectivity, or the relatively low ratio of 
speciﬁ  c to non-speciﬁ  c signal obtained in the human brain,(24)
although a few studies have appeared, reporting reduced 5-HT2
receptor number in drug-free depressed patients. Further studies 
are needed using more selective ligands with higher signal-to-noise ratios, such as [
(11)C]MDL 100907, a promising selective ligand for 
5-HT2A receptors (Table 2.3.6.1). For the serotonin transporter, of 
the available tracers, [(11)C]DASB gives a reasonable signal to noise 
ratio and studies have convincingly shown that standard efﬁ  cacious 
doses of SSRI antidepressants are associated with substantial occu-pancy at this site.
(25) Occupancy at the 5-HTT site occurs after ﬁ  rst 
dosing, and responders and non responders do not differ in terms of SSRI occupancy levels, suggesting 5-HTT occupancy is perhaps a necessary but not sufﬁ  cient explanation for the antidepressant

dosing, and responders and non responders do not differ in terms of SSRI occupancy levels, suggesting 5-HTT occupancy is perhaps a necessary but not sufﬁ  cient explanation for the antidepressant 
effect.Imaging blood-ﬂ  ow change in depressive disorder
Similarly to brain-mapping studies of patients with schizophrenia, 
regional deﬁ  cits of neural activity (indexed by cerebral blood 
ﬂ ow or glucose utilization) can be detected in the ‘resting’ brains 
of depressed patients.(26,27) Many resting-state studies have shown 
a reduction of regional brain functional activity, most frequently reported in the prefrontal cortex, compared with normal controls. However, the exact location of prefrontal change (dorsolateral, ventrolateral, orbitofrontal, and medial frontal areas) has been variably emphasized by different authors.
(26–28)
As demonstrated in schizophrenia, significant associations

(26–28)
As demonstrated in schizophrenia, significant associations 
between cortical activity and cognitive function, symptom clusters, including mood, and response to treatments are apparent.
(27,28)
Similar to schizophrenia, the resting-state functional brain abnor-malities may represent the physiological correlates of aspects of the depressed state such as depressed mood, retardation, or cognitive impairment rather than trait markers of the illness itself.
Psychological challenge paradigms have been applied in studies in 
depressed cohorts to test whether speciﬁ  c brain regions, subserving 
select cognitive processes, are impaired in depressed patients. Currently, however, the majority of challenge paradigms in depressed subjects are undertaken with fMRI methods.
Imaging psychotropic drug action
Of direct clinical relevance are imaging studies of antipsychotic drug action where clinical efﬁ  cacy and side-effects are related to 
receptor occupancy.
(29,30)

(29,30)
Many studies have investigated the occupancy of striatal 
dopamine D1 and D2 and cortical serotonin 5-HT2 receptors by 
neuroleptic drugs. Farde’s group ﬁ  rst demonstrated that clinically 
efﬁ cacious doses of a variety of classical antipsychotics cause 
between 65 per cent and 89 per cent occupancy of central dopa-mine D
2 receptors.(29) Higher receptor occupancy [(gt)85 per cent] 
is associated with an increased incidence of extrapyramidal side effects. Thus, there may be a therapeutic window for occupancy of between 65 per cent and 85 per cent, which is antipsychotic and yet less likely to cause extrapyramidal side effects. In contrast, treatment with classical antipsychotics produces variable levels of occupancy of striatal D
1 receptors. Interestingly, efﬁ  cacious doses

1 receptors. Interestingly, efﬁ  cacious doses 
of the atypical antipsychotic clozapine are associated with a rela-tively low D
2 receptor occupancy (38–63 per cent) and a D1 occu-
pancy of 38 to 52 per cent.(29) This unexpected ﬁ  nding of low D2
receptor occupancy, reproduced in different patient groups with 
both PET and SPET techniques, has challenged theories of a simple relationship between D
2 occupancy per se  and clinical efﬁ  cacy. 
Further evidence for this view comes from studies showing that schizophrenic antipsychotic non-responders have the same levels of dopamine D
2 occupancy as responders and that occupancy 
occurs as rapidly as 2 h after acute administration of the antipsy-chotic yet efﬁ  cacy takes weeks to appear.
PET/SPET is also proving useful in the characterization of 
atypical antipsychotics. The binding of antipsychotic drugs to central 5-HT
2 receptors is a possible candidate for the mechanism

2 receptors is a possible candidate for the mechanism 
of ‘atypicality’ and studies suggest high cortical 5-HT2 occupancy 
with many atypicals including risperidone (80 per cent) and clozapine (84–90 per cent).
(29,30)  Other targets for some atypical 
neuroleptics include the 5-HT1A receptor(31) and in addition, limbic 2.3.6 functional positron emission tomography in psychiatry

SECTION 2  the scientific basis of psychiatric aetiology 190
selectivity (i.e. neuroleptic limbic occupancy > striatal occupancy) 
is an actively researched explanation for atypicality.(32)
So far, the PET and SPET radiotracer techniques have been immediately valuable in assessing the receptor occupancy effects of antipsychotic drugs and of mapping the neural correlates of dys-functional cognitive processes and psychiatric symptoms. Although the applications described have not yielded a diagnostic test, the techniques are undoubtedly providing unique informa tion about the pathophysiology of psychiatric illnesses. Such information is likely to be key for the development of truly novel treatments.
www.crump.ucla.edu/lpp/lpphome.html  A website that gives more 
detailed information on the methodology of PET scanning and clinical applications. 
Journals publishing regular research articles on PET neuroscience include

Journals publishing regular research articles on PET neuroscience include 
Biological Psychiatry, Neuroimage, Synapse, Brain, Human Brain 
Mapping, Journal of Nuclear Medicine, Molecular Psychiatry and Neuropsychopharmacology  amongst others. Annual and biannual 
meetings of the Society of Nuclear Medicine, Organization for Human Brain Mapping and the Society of Cerebral Blood Flow and Metabolism include many ‘cutting edge’ PET neuroscience reports.
 1. Myers, R., Cunningham, V ., Bailey, D., et al. (1996). Quantiﬁ  cation of 
brain function using PET . Academic Press, London.
 2. Frackowiak, R.S.J., Friston, K.J., Frith, C.D., et al. (1997). Human brain 
function.  Academic Press, San Diego, CA.
 3. Gunn, R.N., Gunn S.R. and Cunningham, V .J. (2001). Positron 
emission tomography compartmental models. Journal of Cerebral Blood 
Flow and Metabolism, 6, 635–52.

3. Gunn, R.N., Gunn S.R. and Cunningham, V .J. (2001). Positron 
 4. Fischer, P .M., Meltzer, C.C., Ziolko, S.K., et al. (2006). Capacity for 
5-HT1A-mediated autoregulation predicts amygdala reactivity. Nature Neuroscience, 11, 1362–3.
 5. David, S.P ., Murthy, V .M., Rabiner, E.N., et al. (2005). A functional 
genetic variation of the serotonin (5-HT) transporter affects 
5-HT1A receptor binding in humans. Journal of Neuroscience ,
10, 2586–90.
 6. Wong, D.F., Wagner, H.N., Tune, L.E., et al. (1986). Positron emission 
tomography reveals elevated D2-dopamine receptors in drug-naïve schizophrenia. Science ,234, 1558–63.
 7. Farde, L., Wiesel, F.-A., Stone-Elander, S., et al. (1990). D2 dopamine 
receptors in neuroleptic naive schizophrenic patients. Archives of 
General Psychiatry ,47, 213–19.
 8. Sedvall, G. and Farde, L. (1995). Chemical brain anatomy in

 8. Sedvall, G. and Farde, L. (1995). Chemical brain anatomy in 
schizophrenia. Lancet ,346, 743–9.
 9. Hietala, J., Syvalahti, E., Vuorio, K., et al. (1995). Presynaptic 
dopamine function in striatum of neuroleptic naive schizophrenic patients. Lancet ,346, 1130–1.
10. Guillin, O., Abi-Dargham, A. and Laruelle, M. (2007). Neurobiology 
of Dopamine in Schizophrenia. International Review of Neurobiology ,
78, 1–39.
11. Volkow, N.D., Wang, G.-J., Fowler, J.S., et al. (1994). Imaging 
endogenous dopamine competition with 11C-raclopride in the human brain. Synapse ,16, 255–62
12. Laruelle, M., Abi-Dargham, A., van Dyck, C.H., et al. (1996). 
Single photon emission computerized tomography imaging of amphetamineinduced dopamine release in drug-free schizophrenia 
subjects. Proceedings of the National Academy of Sciences of the United 
States of America ,93, 9235–40.

13. Weinberger, D.R. and Berman, K.F. (1996). Prefrontal function in 
schizophrenia: confounds and controversies. Philosophical Transactions 
of the Royal Society of London. Series B: Biological Sciences ,351,
1495–503.
14. Chuam, S.E. and McKenna, P .J. (1996). Schizophrenia—a brain disease? 
A critical review of structural and functional cerebral abnormality in the disorder. British Journal of Psychiatry
,166, 563–82.
15. Frith, C.D., Friston, K.J., Herold, S., et al. (1995). Regional
brain activity in chronic schizophrenic patients during the performance of a verbal ﬂ  uency task. British Journal of Psychiatry ,
167, 343–9. 
16. Liddle, P .F., Friston, K.J., Frith, C.D., et al. (1992). Patterns of cerebral 
blood ﬂ  ow in schizophrenia. British Journal of Psychiatry ,160,
179–86.
17. Dolan, R.J., Bench, C.J., Liddle, P .F., et al. (1993). Dorsolateral

179–86.
17. Dolan, R.J., Bench, C.J., Liddle, P .F., et al. (1993). Dorsolateral 
prefrontal cortex dysfunction in the major psychoses; symptom or disease speciﬁ  city? Journal of Neurology, Neurosurgery and Psychiatry ,
56, 1290–4.
18. Andreasen, N.C., O’Leary, D.S., Flaum, M., et al. (1997). Hypofrontality 
in schizophrenia: distributed dysfunctional circuits in neurolepticnaive patients. Lancet ,349, 1730–4.
19. Sabri, O., Erkwoh, R., Schreckenberger, M., et al. (1997). Correlation of 
positive symptoms exclusively to hyperperfusion or hypoperfusion of cerebral cortex in never-treated schizophrenics. Lancet ,349,
1735–9.
20. Spence, S.A., Hirsch, S.R., Brooks, D.J., et al. (1998). Prefrontal cortex 
activity in people with schizophrenia and control subjects. Evidence from positron emission tomography for remission of ‘hypofrontality’ with recovery from acute schizophrenia. British Journal of Psychiatry ,
172, 316–23.

21. Callicott, J.H., Mattay, V .S., Verchinchi, B.A., et al. (2003). Complexity 
of prefrontal cortical dysfunction in schizophrenia: more than up or down. American Journal of Psychiatry ,12, 2209–15.
22. Pike, V ., McCarron, J.A., Lammerstma, A.A., et al. (1995). First 
delineation of 5-HT1A receptors in the living human brain using (11)CWAY-100635. European Journal of Pharmacology ,283,
R1–R3.
23. Sargent, P .A., Kjaer, K.H., Bench, C.J., et al. (2000). Brain serotonin1A 
receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Archives of General Psychiatry ,2, 174–80.
24. Pike, V . (1993). Positron emitting radioligands for studies 
in vivo— probes for human psychopharmacology. Journal of 
Psychopharmacology ,7, 139–58.
25. Meyer, J. (2007). Imaging the serotonin transporter during major 
depressive disorder and antidepressant treatment. Journal Psychiatry 
and Neuroscience ,2, 86–102.

26. Goodwin, G. (1996). Functional imaging, affective disorder and 
dementia. British Medical Bulletin ,52.
27. Drevets, W.C., Price, J.L., Simpson, J.R., et al. (1997). Subgenual 
prefrontal cortex abnormalities in mood disorders. Nature ,
386, 824–7.
28. Grasby, P .M. and Bench, C.J. (1997). Neuroimaging of mood disorders. 
Current Opinion in Psychiatry ,10, 73–8.
29. Farde, L., Nordstrom, A.-L., Wiesel, F.A., et al. (1992). Positron 
emission tomographic analysis of central D1 and D2 dopamine 
receptor occupancy in patients treated with classical neuroleptics and 
clozapine. Relation to extrapyramidal side effects. Archives of General 
Psychiatry ,49, 538–54.
30. Nyberg, S., Farde, L., and Erikson, L. (1993). 5-HT2 and D2 dopamine

30. Nyberg, S., Farde, L., and Erikson, L. (1993). 5-HT2 and D2 dopamine 
receptor occupancy in the living human brain: a PET study with 
risperidone. Psychopharmacology ,110, 265–72.

191
31. Bantick, R.A., Deacon, J.F., and Grasby, P .M. (2001) The 5-HT1A 
receptor in schizophrenia: a promising target for novel atypical neuroleptics? Journal of Psychopharmacology ,1,
 37–46.
32. Bressan, R.A., Erlandsson, K., Jones, H.M. et al. (2003) Optimizing 
limbic selective D2/D3 receptor occupancy by risperidone: a [123I]-epidepride SPET study. Journal of Clinical Psychopharmacology, 
1, 5–14.
2.3.7 Structural magnetic 
resonance imaging
Magnetic resonance imaging ( MRI ) is a versatile and evolving

1, 5–14.
Magnetic resonance imaging ( MRI ) is a versatile and evolving 
technology for visualizing the structure, function, and metabolism of the living human brain. All kinds of MRI data can be acquired without exposing subjects to ionizing radiation or radioactive iso-topes. Installing the hardware for MRI represents a major capital investment, of approximately £1.5 million. For these three reasons of versatility, safety, and (relative) affordability, MRI continues to be the dominant brain-imaging technique in psychiatric practice and research.
In this chapter, we introduce the principles and practicalities of 
MRI and describe common methods of structural MRI data acqui-sition and analysis. Chapter 2.3.8 on functional MRI provides greater detail on statistical issues arising in image analysis.
Magnetization
If iron ﬁ  lings are scattered on a piece of paper they will be oriented

If iron ﬁ  lings are scattered on a piece of paper they will be oriented 
at random. If a bar magnet is then placed under the paper, the iron ﬁ lings will align themselves so that each ﬁ  ling lies parallel to the 
magnetic ﬁ  eld produced by the magnet. More technically, we can 
say that iron ﬁ  lings have a susceptibility to be magnetized by a static 
magnetic ﬁ  eld.
Susceptibility refers both to the effect of a magnetic ﬁ  eld on an 
object, and the effect of that object on the ﬁ  eld. Paramagnetic 
materials, like some metals, tend to be attracted by magnets and cause a local increase in the magnetic ﬁ  eld strength. Diamagnetic 
materials, like carbon and many organic compounds, tend to be repulsed by magnets and cause a local decrease in ﬁ  eld strength.
The brain also has a susceptibility to be magnetized. It is largely 
composed of water and each molecule of water comprises, of course, two hydrogen atoms and one oxygen atom. The hydrogen

composed of water and each molecule of water comprises, of course, two hydrogen atoms and one oxygen atom. The hydrogen 
nucleus is a single positively charged proton, which has a dynamic 
property called spin. Like all moving charged particles, spinning protons generate a magnetic ﬁ  eld. The axis of the magnetic dipole 
generated by a spinning proton is sometimes called its magnetic moment, and is drawn as a vector.
When the brain is placed in a strong magnetic ﬁ  eld, the spinning 
protons align themselves with the external ﬁ  eld, just as iron ﬁ  lings 
align themselves to the ﬁ  eld of a bar magnet. The angle of align-
ment between each proton’s moment and the (longitudinal) axis of the external magnetic ﬁ  eld is α. Protons obey the laws of quantum 
mechanics, and so two modes of alignment or spin states are pos-sible, one with the magnetic moment in the direction of the ﬁ  eld

mechanics, and so two modes of alignment or spin states are pos-sible, one with the magnetic moment in the direction of the ﬁ  eld 
(α = 0°) and one with the moment in the opposite direction ( α = 
180°). Depending on the strength of the applied ﬁ  eld, the spin 
states have slightly different probabilities, with those protons aligned in the direction of the ﬁ  eld in excess by about 5 ppm at an 
external ﬁ  eld strength of 1.5 T. (Magnetic ﬁ  eld strength is meas-
ured in units of gauss ( G) or tesla ( T): 1 T = 10 000 G. The earth’s 
magnetic ﬁ  eld is approximately 0.5 G; a child’s toy magnet has a 
ﬁ eld of around 10 G.)
Thus, if the magnetic moments for all spinning protons are 
averaged, the net, or bulk, magnetization vector for the brain as a whole will have α = 0°. The length of the net magnetization 
vector then represents the strength of longitudinal magnetization (Fig. 2.3.7.1).
Protons aligned with a static magnetic ﬁ  eld are not static them-

selves, they rotate or precess at very high frequency around the axis of the external ﬁ  eld. The precession frequency, or Larmor 
frequency, is constant for a given type of atomic nucleus and exter-nal ﬁ  eld strength. For protons, the Larmor frequency at 1.5 T is 
63.9 MHz. However, although all hydrogen nuclei in the brain precess at the same frequency in the same ﬁ  eld, they will not all 
precess with the same phase. At any given time, different nuclei 
have reached a different point in their rotation around the external ﬁ eld axis.
Nuclear magnetic resonance
When a wineglass is tapped by a knife, it produces a high-pitched

When a wineglass is tapped by a knife, it produces a high-pitched 
sound of characteristic frequency. If a singer can exactly match that frequency with her voice then the glass will resonate and may break. The basic idea is that if an object has a characteristic frequency of oscillation, exposing it to energy precisely at that frequency will cause a change in physical state.
Analogously, if we supply a pulse of radio-frequency energy at 
(and only at) the Larmor frequency to a brain located in a mag-netic ﬁ  eld, the protons within the brain will absorb the energy and 
resonate—this is nuclear magnetic resonance ( NMR )—and their 
angle of alignment α with the external ﬁ  eld will increase. If sufﬁ  -
cient energy is supplied to cause α = 90 °, the radio-frequency pulse 
is called a ‘90 ° pulse’ . If the net magnetization vector is ﬂ  ipped to

is called a ‘90 ° pulse’ . If the net magnetization vector is ﬂ  ipped to 
an angle α = 180 °, the radio-frequency pulse is called a ‘180 ° pulse’ . 
At the same time as the angle of alignment is increased by radio-
frequency irradiation, the phase of precession becomes coherent over all protons. In other words, in place of the random variation in the phase of precession that existed before the radio-frequency pulse, protons are now ‘marching in step’ with each other around the axis of the external ﬁ  eld.
After the radio-frequency pulse has ceased, the resonating nuclei 
gradually relax back to the equilibrium state of random precession in alignment with the external ﬁ  eld. The two components of this 
relaxation process are characterized by relaxation times. The ﬁ  rst 
relaxation time ( T
1), also called the spin-lattice relaxation time,

1), also called the spin-lattice relaxation time, 
describes the time taken for the strength of longitudinal magneti-zation to return to 63 per cent of its value before radio-frequency irradiation. This is a measure of the time taken for α to return to 
zero having been ﬂ  ipped to 90 ° or 180 °.T
1 is determined by interac-
tions between protons and their long-range (molecular) environment 2.3.7 structural magnetic resonance imaging

SECTION 2  the scientific basis of psychiatric aetiology 192
or lattice. The second relaxation time ( T2), also called the spin–
spin relaxation time, describes the time taken for the ﬂ  ipped 
nuclei to stop ‘marching in step’ around the axis of the ﬁ  eld. 
This process of dephasing begins as soon as the radio-frequency 
pulse stops, but its rate is determined by the immediate (atomic) 
environment of the protons. Small variations in the applied mag-
netic ﬁ  eld accentuate spin–spin relaxation, resulting in an observed 
relaxation time T2* which is somewhat faster than the ‘true’ relaxa-
tion time T2 that would have been observed in an ideally homoge-
neous ﬁ  eld.As protons relax, they release the energy absorbed from the 
radio-frequency pulse in the form of a weak radio-frequency 
signal, which decays at a rate normally determined by T2*. This 
process is called free induction decay, and the emitted signal forms 
the data from which magnetic resonance images are ultimately

the data from which magnetic resonance images are ultimately 
constructed.
Magnetic resonance imaging
Spin echo sequence
A widely used MRI technique is the spin echo sequence. A 90 °
radio-frequency pulse is repetitively applied to the brain with a 
constant repetition time (TR ms) between consecutive pulses. 
Following each 90 ° pulse, protons are excited and then relax. The 
dephasing component of relaxation can be reversed by applying a 
second 180 ° pulse some time (TE/2 ms) after the 90 ° pulse. 
Following the ﬁ  rst 90 ° pulse, protons immediately begin to precess 
idiosyncratically and the emitted signal decays. By reversing this 
process, the 180 ° pulse causes rephasing and an increase in emitted 
signal which has a maximum or echo at TE ms (time to echo) after 
the initial 90 ° pulse (Fig. 2.3.7.2).

The spatial location of the radio-frequency signal emitted by free 
induction decay in a given volume of the brain is encoded in three 
spatial dimensions by slice-selective radio-frequency irradiation 
combined with frequency- and phase-encoding gradients. T o 
improve scan time, multiple slices can be excited in an interleaved 
fashion (multislice acquisition). This means that after the output 
signal is detected from one slice, and while the net magnetization 
vector is relaxing back to its equilibrium state, other slices can be 
excited. The in-plane resolution (voxel size) of the image is deter-
mined by the ﬁ  eld of view and the number of voxels in the image. 
Typically, in-plane resolution at 1.5 T is in the order of 0.5 to 2 mm, 
and slice thickness is 2 mm or more.
Tissue contrast

The outstanding advantage of MRI for the anatomical examination 
of the brain is the easily visible contrast in the images between grey 
matter, white matter, and cerebrospinal ﬂ  uid. In particular, contrast 
between parenchymal tissues (grey and white matter) has made 
MRI the imaging research tool of choice for identifying subtle 
cortical abnormalities in a wide variety of psychiatric disorders.
Tissue contrast in magnetic resonance images is determined by 
differences in the density of protons, and their physical and chemi-
cal environment. A tissue such as the cerebrospinal ﬂ  uid, that is 
Fig. 2.3.7.2 Spin echo pulse sequence. A 90 ° excitation pulse of radio-frequency 
energy is immediately followed by exponential decay of the T2-weighted signal.

energy is immediately followed by exponential decay of the T2-weighted signal. 
A 180 ° pulse TE/2 ms later causes rephasing of proton spins and an exponential 
increase in T2-weighted signal with maximum (echo) TE ms after the 90 ° 
pulse. Images are acquired at TE (thick arrow). The protons are allowed to relax 
completely before the next 90 ° pulse, TR ms after the previous excitation.
Fig. 2.3.7.1 Net magnetization vector.
(a) In a static magnetic ﬁ  eld, the vector is aligned parallel to the longitudinal z axis 
of the ﬁ  eld and a = 0.
(b) Immediately after a 90 ° excitation pulse of radio-frequency energy at Larmor 
frequency, the angle of alignment a is increased (transverse magnetization) and 
the phase of precession in the x–y plane is coherent over all protons in the brain. 
As protons relax following excitation, the angle of the net vector becomes smaller

As protons relax following excitation, the angle of the net vector becomes smaller 
(return of longitudinal magnetization) and the phase of precession becomes more 
variable from one proton to another (dephasing).

193
composed largely of water, will have a lower proton density than 
parenchymal brain tissues. The physicochemical environment of protons has a marked effect on spin-lattice relaxation. If protons are mainly in freely diffusing water molecules, as they are in cere-brospinal ﬂ  uid, T
1 will be prolonged, whereas if they are mainly 
bound to large macromolecules, as they are in fat, T1 will be short 
(Table 2.3.7.1). Since grey matter contains proportionally less fat than myelinated white matter, T
1 is longer for grey matter. Spin–
spin relaxation is likewise determined, in part, by the immediate physical environment of protons in the tissue; liquid tissues will have prolonged T
2 times compared with solid tissues. Other effects 
on apparent relaxation times ( T2*) include minute ﬂ  uctuations or 
inhomogeneities in the strength of the external magnetic ﬁ  eld, which 
may be due to the local paramagnetic effects of iron-containing compounds such as haemoglobin.

The parameters of the spin echo pulse sequence, repetition time 
(TR), and time to echo (TE), can be judiciously adjusted to acquire images that are sensitive to or weighted by one or other of these possible sources of tissue contrast.
If TR is long (>1000 ms) and TE is short (<20 ms), contrast in 
the images will be weighted by differences between tissues in pro-ton density. Proton-density-weighted images show good contrast between relatively hyperintense parenchymal tissue and hypoin-tense cerebrospinal ﬂ  uid (Plate 7).
If TR is short (<1000 ms) and TE is also short (<20 ms), contrast 
in the images will be weighted by tissue differences in spin-lattice 
relaxation. T
1-weighted images show excellent contrast between 
hyperintense white matter and relatively hypointense grey matter (Plate 7). For this reason, T

1-weighted images are widely used to 
measure quantitative abnormalities in size or shape of the cerebral cortex.
If TR is long (>1000 ms) and TE is also long (>20 ms), contrast 
in the images will be weighted by tissue differences in spin–spin relaxation. T
2-weighted images show strong contrast between 
hyperintense cerebrospinal ﬂ  uid and parenchymal tissues (Plate 7), 
unless there is congestion or oedema of the parenchyma, in which case the T
2-weighted signal will be increased. For this reason, T2-
weighted images are widely used to identify acute, inﬂ  ammatory, 
and ischaemic lesions.
Structural imaging sequences
An enormous range of sequences are available for brain imaging. For example, fast spin echo imaging provides a pair of dual-echo images with complementary tissue contrasts (proton density and T

2-weighted) for no increase in scan time over the spin-echo 
sequence. Spins can also be manipulated through changes in the applied magnetic ﬁ  eld gradients. These sequences yield images of high-spatial resolution and a range of contrasts. Additionally, there 
are methods for suppressing signals due to blood ﬂ  ow or fat, 
improving signals from pathology.
Diffusion-weighted imaging
Diffusion-weighted imaging can provide information about the organization of white matter tracts in the brain that cannot be obtained by other MRI methods.
The basic idea is that protons move within and between cells by

The basic idea is that protons move within and between cells by 
random motion. Typically, a proton may travel around 20 μm in 100 ms by this Brownian motion or diffusion. The rate of proton diffusion is related to how constrained they are by physical barriers such as myelinated cell membranes. The rate of diffusion affects the spin–spin relaxation time, with rapidly diffusing protons tend-ing to relax more quickly. T o acquire images that are weighted by differences in diffusion, two extra gradients are brieﬂ  y applied dur-
ing a spin echo sequence.
(1)
White matter is generally hyperintense in diffusion-weighted 
imaging because closely packed axonal tracts provide the greatest barrier to the free diffusion of water in the brain. Furthermore, it is possible to deduce from diffusion-weighted imaging data how compactly organized the white matter is, and even to estimate in what direction the ﬁ  bre tracts are oriented (Plate 8). This informa-

tion is of considerable interest to psychiatry, since the pathology of many psychiatric disorders may involve the axonal connections between multiple cortical areas.
(2)
Safety
MRI is absolutely contraindicated in patients who have any strongly magnetized metal object in their heads. This includes aneurysm clips, reconstructive metal plates, traumatically embedded metal fragments, or implanted electronic devices such as cardiac pace-makers. It is advisable to screen all subjects undergoing MRI by questionnaire for possible contraindications. A skull radiograph is a useful preliminary examination if there is any doubt about the presence of intracranial metal. All subjects need to provide informed consent in writing.
Static magnetic ﬁ  elds used in MRI cause no harmful effects to 
biological tissue. Rapid switching of ﬁ  eld gradients can induce

biological tissue. Rapid switching of ﬁ  eld gradients can induce 
electrical currents in tissue, but at the switching speeds used in MRI these induced currents are several times less than needed for muscle contraction. Since radio-frequency energy can cause heat-
ing, limits to the amounts of energy absorbed are set by national 
standards.
Artefacts
Quality assurance protocols and diligent hardware servicing are necessary to maintain high standards in MRI. Image artefacts refer to loss of image quality (i.e. spatial resolution or tissue contrast) owing to a speciﬁ  c cause. It is often possible to effect a remedy and 
an awareness of their causes can often pre-empt the problem.
Movement

Movement
Subject motion is the most common artefact and has two compo-nents: voluntary and involuntary (physiological). The result of voluntary motion during acquisition may be an obvious blurring (Plate 7). The cooperation of subjects is vital and special regard is Table  2.3.7.1  Relaxation times at 1.5 T for different tissue types
Tissue type T1 (ms) T2 (ms)
Grey matter 980–1040 64–71
White matter 740–770 64–70CSF >2000 >300Fat (at 1 T) 180 90
CSF, cerebrospinal ﬂ  uid.2.3.7 structural magnetic resonance imaging

SECTION 2  the scientific basis of psychiatric aetiology 194
required for children, the elderly, and those with neurological 
or psychiatric disorders who may ﬁ  nd the MRI environment dis-
concerting. The subject’s head may be physically restrained by additional padding and by Velcro straps placed across the fore-head. Involuntary motion arises primarily from the cardiorespira-tory cycle causing pulsation of the blood vessels and cerebrospinal ﬂ uid. This is most apparent in structural images showing major 
arteries.
Susceptibility
Where two materials with very different susceptibilities are closely adjacent, there may be severe distortion of the magnetic ﬁ  eld,

arteries.
Where two materials with very different susceptibilities are closely adjacent, there may be severe distortion of the magnetic ﬁ  eld, 
causing artefactual loss or exaggeration of the magnetic resonance signal. This is clearly seen in an image acquired with a metallic clip placed close to the scalp (Plate 7). Ferromagnetic (highly paramag-netic) materials that may cause artefacts include metallic dental ﬁ llings and plates, hairgrips, ear or nose rings, and even some 
cosmetics. A less obvious form of susceptibility artefact arises if more (diamagnetic) tissue is situated at one end of the image ﬁ  eld 
of view than the other. A ﬁ  eld gradient is set-up across the image 
resulting in signal loss. This is termed bulk susceptibility artefact and is often seen in images of both the head and neck (Plate 7).
Partial volume

Voxel sizes are larger than some scales of anatomical organization in the brain. A voxel may represent a heterogeneous mixture of tissue classes, or be only partially occupied by tissue of a single type. This partial volume artefact is particularly evident at the interface between cortical grey matter and sulcal cerebrospinal ﬂ  uid, and at 
the interface between cortical grey matter and central white matter. It causes error in the estimation of tissue class volumes.
MRI hardware
Superconducting magnet
The superconducting magnets used for MRI require liquid helium cooling equipment to keep the temperature low enough (4 K) for 
superconduction. Cooling consumes the majority of the supplied power. Only a small current is initially required to generate the ﬁ eld, which is then self-sustaining.

Small variations in the homogeneity of the magnetic ﬁ  eld give 
rise to distortions and artefacts. The ﬁ  eld is minutely adjusted to 
improve homogeneity using additional magnets in an automated procedure known as shimming.
Magnetic ﬁ  eld gradients are essential to MRI. Rapid switching 
of gradient coils produces the loud ‘knocking’ sound associated with magnetic resonance scanners. Three orthogonal gradients are available which are coupled to generate gradients in any direction.
Radio-frequency coil
The function of the radio-frequency coil is two-fold—to transmit the radio-frequency pulses of the imaging sequences and to receive the emitted signal. Head coils used for neuroimaging ﬁ  t snugly

The function of the radio-frequency coil is two-fold—to transmit the radio-frequency pulses of the imaging sequences and to receive the emitted signal. Head coils used for neuroimaging ﬁ  t snugly 
over the subject’s head, and are often of a three-dimensional design with good sensitivity throughout the volume they enclose. Surface coil designs are used to image small regions with high-spatial resolution, and phased-array coils combine several surface coils for more extensive coverage.Computers
MRI produces large quantities of data, which require rapid process-ing and storage so that images may be viewed and other sequences prescribed during the same session. The computer system is integral to the machine and contains specialized hardware and software for data acquisition and image reconstruction, as well as control of the scanner.
The scanner suite
The room housing the scanner must be specially designed. It must have a reinforced ﬂ  oor and be environmentally controlled to main-

tain a constant temperature and humidity. The walls and ceiling contain a magnetic shield, which both prevents leakage of the ﬁ  eld 
outside the room and stops FM radio broadcasts from being picked up by the radio-frequency coil.
MRI studies
Case-control design
Structural MRI studies in psychiatry have commonly adopted a cross-sectional or case-control design. This involves scanning two groups of subjects, patients, and matched controls, on a single occasion. The objective is generally to identify anatomical differ-ences in brain structure between cases and controls. In evaluating or planning such a study, it is important to pay attention to several design issues, some of which are summarized below.
Power

Power
What is the power of the study to refute the null hypothesis (zero anatomical difference between the case and control populations) when it is not true? In general, the power of a study is proportional to the sample size (the number of subjects scanned), the effect size (the anatomical difference between populations), and the probability threshold or p value adopted for hypothesis testing. The 
p value will often be decided in relation to the number of tests 
conducted—the greater the number of tests, the smaller is the appropriate p value. Therefore, the risk of low power and associated 
type 2 error is likely to be greatest when differences between two small groups have been multiply tested on the basis of many anatomical variables.
Representativeness

What population is represented by the sample of patients studied, and is this the population of interest? If the ambition of the study is to make inferences about the population of patients with, say, manic-depressive disorder, then it is important that the diagnosis is made according to standard and reliable criteria and that the sampling procedure is such that any patient in that population has an equal chance of being included in the study. This means that the authors of the study will need to sample cases from general practice and the community as well as from hospital clinics and wards. Sampling hospital patients is generally much easier; the patients 
are already well characterized and hospital treatment facilities are

are already well characterized and hospital treatment facilities are 
likely to be relatively few in number and close to the scanning unit. However, if only hospital patients are sampled, it follows that infer-ence can only be made about the population of hospital patients, rather than the larger and more general population of individuals with the disorder.

195
Heterogeneity
Diagnostic categories in psychiatry may subsume considerable 
heterogeneity in terms of phenomenology and aetiology. For example, patients with a diagnosis of schizophrenia may differ profoundly in terms of positive or negative symptom proﬁ  les, 
cognitive deﬁ  cit, and genetic or environmental risk factors. These 
natural sources of heterogeneity may be compounded by differ-ences in treatment. Any or all of these factors may affect brain structure. Studies that simply ignore heterogeneity, or attempt to deal with it by post hoc  statistical correction, may have less power 
to detect a group difference than studies which deﬁ  ne cases accord-
ing to reﬁ  ned or subdiagnostic criteria. Thus, studying a sample of 
schizophrenic patients with high negative symptom scores and marked working memory deﬁ  cits may be more likely to reveal ana-
tomical abnormalities of frontal cortex than studying an unreﬁ  ned 
sample of patients with schizophrenia.
Matching

Matching
Ideally, the control or comparison subjects should be indistinguish-able from the patients in every characteristic apart from features of the disorder. For example, it is important that cases and controls should be matched for age, handedness, and sex, since all of these factors may affect brain structure. Unfortunately, there are a number of other possible confounding factors that are not so obvi-ously unrelated to presence of the disorder. For example, an unre-ﬁ ned sample of patients with schizophrenia will generally have 
lower IQ and smaller head size than an age- and sex-matched group of comparison subjects. Should we try to correct these differences 
as if they were spurious (by either reﬁ  ned sampling or post hoc  sta-

tistical modelling), or should we accept that they represent real fea-tures of the disorder? In practice, most published studies tend to correct group differences on global variables by statistical model-ling in order to focus attention on regional differences that may be more interesting. A comparable problem arises in relation to medication.
Other designs
A probable future trend in psychiatric MRI research over the next few years is that the hypotheses under investigation will become more concerned with aetiological mechanisms and pathogenetic models and less concerned with the basic question of whether a given group of patients has abnormal brain structure. This shift in hypothetical interest will dictate a shift in design away from case-control or cross-sectional studies.
Longitudinal designs, in which a cohort of volunteers or patients

Longitudinal designs, in which a cohort of volunteers or patients 
are scanned repeatedly over a period of months or years, are a pow-erful way of demonstrating normal and abnormal developmental changes in brain structure.
(3) They have the obvious disadvantage 
that they are time consuming to complete and subjects may not attend for multiply repeated examination.
Genetic designs involve subjects that are deﬁ  ned genotypically, 
rather than phenotypically. Imaging studies of monozygotic twins discordant for a disorder,
(4) and of families multiply affected by a 
disorder, are examples of genetic designs in which there may be complete knowledge about the proportion of genetic information that is shared between subjects but incomplete knowledge about the genetic constitution of each subject.Overall, there is no single perfect design for an imaging study. 
Often designing a study will entail ﬁ  nding pragmatic and arguably

Often designing a study will entail ﬁ  nding pragmatic and arguably 
justiﬁ  able solutions to problems. Furthermore, the ‘goodness’ of a 
design can really only be judged in relation to the hypothesis under investigation and the methods of analysis applied to the data. The best imaging studies will convey a sense that the design is both ingenious and inevitable, given the hypothesis and available methods, and will also include a frank discussion of the limitations or implications of the particular design adopted.
Data analysis
Clinical analysis

Structural MRI is most often used in clinical practice to exclude non-psychiatric causes for psychopathology. Clinical examination of these cases may also sometimes reveal abnormalities such as hippocampal sclerosis or callosal agenesis which suggest that psy-chopathology has been determined by birth injury or abnormal development. In assessment of a patient with dementia, MRI may usefully demonstrate signs of vascular disease (such as infarcts or periventricular white matter changes), or a focal pattern of grey matter atrophy suggestive of Pick’s disease (frontal cortex) or Huntington’s disease (caudate nucleus and frontal cortex). All of these abnormalities may be detected simply by skilled visual exam-ination of the data. However, clinical diagnosis of the subtler abnor-malities associated with, say, schizophrenia, obsessive–compulsive disorder, or autism require quantitative analysis of the patient’s data and access to normative MRI measurements on appropriately matched samples of

with, say, schizophrenia, obsessive–compulsive disorder, or autism require quantitative analysis of the patient’s data and access to normative MRI measurements on appropriately matched samples of the general population. Neither quantitative analysis nor normative databases are widely used in current radio-logical practice, thus limiting the value of MRI to clinical psychia-try, but this may be expected to change in the future.

Quantitative analysis
There are broadly two requirements for quantitative analysis of structural MRI data. The ﬁ  rst is to measure the anatomical struc-
ture of the brain (this is often called morphometry). The second is to test hypotheses of interest on the basis of these morphometric variables.
(5) Here we shall focus on morphometry.
(a) Morphometry
A widely used method of measuring brain structure from magnetic resonance images is based on the hypothetical expectation that one or more anatomically deﬁ  ned regions of the brain are particularly 
relevant to the disorder.
(6) The area or volume of each of these 
regions of interest ( ROIs) can then be measured directly by drawing 
a line around the region on a computerized display of the data and counting the number of voxels enclosed by the line. Measurements of several ROIs may be combined to produce summary measures of asymmetry
(7) or of spatially distributed anatomical systems. The

(7) or of spatially distributed anatomical systems. The 
advantages of ROI morphometry are that it is conceptually simple and that it allows measurement of structures (e.g. the hippocam-pus) or parts of structures (e.g. segments of the corpus callosum) that may be difﬁ  cult to measure otherwise. Some familiar disadvan-
tages are that it is time consuming and imperfectly reliable. More fundamentally, ROI morphometry is of limited use if it is not obvi-ous in advance what the region of interest is, or there are several possible regions of abnormality (as is likely if the disorder is deter-mined by an insult early in the course of brain development).2.3.7 structural magnetic resonance imaging

SECTION 2  the scientific basis of psychiatric aetiology 196
Computerized techniques are varied, but commonly adopt an 
approach summarized in Plate 9. In this scheme, the ﬁ  rst step in 
image processing is removal of extracerebral tissues like skull and scalp leaving an image of the brain alone. The brain image is then segmented into the three main tissue classes. There are a variety of techniques for segmentation or brain tissue classiﬁ  cation,
(8) but gen-
erally the quality of segmentation is improved if multiple images of different contrasts (e.g. proton density, T
2-weighted) are available.
Once the brain image has been divided into its component classes,

Once the brain image has been divided into its component classes, 
or even prior to segmentation, it can be automatically registered in a standard anatomical space. The value of making this transforma-tion is potentially two-fold. First, it then becomes possible to com-pare brain structure between individuals at the spatial resolution of the image, that is in terms of the percentage occupancy of each voxel by each tissue class. This means that one is able ultimately to test anatomical differences between groups over the whole brain in detail, without having to assume a priori that pathological change is located in a particular region.
(9,10)  The second major advantage

(9,10)  The second major advantage 
of image registration is that the parameters of the transformation used to align the image with the template may themselves be used as measures of brain structure. Thus, if an image represents a brain that is structurally abnormal in some way, the mathematical defor-mation which must be applied to align it with a standard template may be abnormally great.
(11)
(b) Statistical testing
Morphometric variables can be used to test hypotheses by a variety of statistical analyses. For example, the null hypothesis of zero dif-ference in brain structure between two groups can be addressed by at-test of a single ROI or by many thousands of t-tests of, say, grey

matter occupancy measured at each and every voxel. Similarly hypotheses concerning the relationship between brain structure and psychological function can be addressed by testing the correla-tion between a morphometric variable and the subjects’ scores on a psychometric instrument. Alternatively, the relationships between several morphometric variables may be explored by multivariate methods such as partial least squares.
(12)
MRI theory and practice—McRobbie, D.W., Moore, E.A., Graves, M.J., et al.
(2007). MRI from picture to proton  (2nd edn). Cambridge University 
Press, Cambridge.
Reviews of structural imaging in psychiatry—Symms, M., Jager, H.R., 
Schmierer, K., et al.  (2004). A review of structural magnetic resonance 
neuroimaging. Journal of Neurology, Neurosurgery, and Psychiatry ,75,
1235–44.
Hyman, S.E. (2007). Can neuroscience be integrated into the DSM-V? 
Nature Reviews Neuroscience ,8, 725–32.

1235–44.
Online repository of methods and data—The Internet Brain Segmentation 
Repository (http://www.cma.mgh.harvard.edu/ibsr/) provides manually guided expert segmentation results along with magnetic resonance brain image data.
 1. Basser, P .J. and Jones, D.K. (2002). Diffusion tensor MRI: theory, 
experimental design and data analysis—a technical review. NMR in 
Biomedicine ,15, 456–67.
 2. Taylor, W.D., Hsu, E., Krishnan, K.R.R., et al.  (2004). Diffusion tensor 
imaging: background, potential and utility in psychiatric research. Biological Psychiatry ,55, 201–7. 3. Giedd, J.N., Blumenthal, J., Jeffries, N.O., et al. (1999). Brain 
development during childhood and adolescence: a longitudinal MRI 
study. Nature Neuroscience ,2, 861–3.

 4. McDonald, C., Bullmore, E.T., Sham, P .C., et al. (2004). Association 
of genetic risks for schizophrenia and bipolar disorder with speciﬁ  c 
and generic brain structural endophenotypes. Archives of General 
Psychiatry ,61, 974–84.
 5. Bullmore, E.T., Suckling, J., Overmeyer, S., et al.  (1999). Global, voxel 
and cluster tests, by theory and permutation, for a difference between two groups of structural MR images. IEEE Transactions on Medical 
Imaging ,18, 32–42.
 6. Wright, I.C., Rabe-Hesketh, S., Woodruff, P .W.R., et al.  (2000). The
American Journal of Psychiatry ,157, 16–25.
 7. Shenton, M.E., Dickey, C.C., Frumin, M., et al.  (2001). A review of MRI 
ﬁ ndings in schizophrenia. Schizophrenia Research ,49, 1–52.
 8. Zhang, Y., Brady, M., and Smith, S. (2001). Segmentation of brain 
MR images through a hidden Markov random ﬁ  eld model and the

MR images through a hidden Markov random ﬁ  eld model and the 
expectation-maximisation algorithm. IEEE Transactions on Medical 
Imaging ,20, 45–57.
 9. Ashburner, J. and Friston, K.J. (2000). Voxel-based morphometry—the 
methods. NeuroImage ,11, 805–21.
10. Ananth, H., Popescu, I., Critchley, H.D., et al.  (2002). Cortical and 
subcortical gray matter abnormalities in schizophrenia determined 
through structural magnetic resonance imaging with optimized voxel-based morphometry. The American Journal of Psychiatry ,159,
1497–505.
11. Chung, M.K., Worsley, K.J., Robbins, S., et al. (2003). Deformation-
based surface morphometry applied to gray matter deformation. 
NeuroImage ,18, 198–213.
12. Nestor, P .G., O’Donnell, B.F., McCarley, R.W., et al. (2002). A new

12. Nestor, P .G., O’Donnell, B.F., McCarley, R.W., et al. (2002). A new 
statistical method for testing hypotheses of neuropsychological/MRI relationships in schizophrenia: partial least squares analysis. Schizophrenia Research ,53, 57–66.
2.3.8 Functional magnetic 
Functional magnetic resonance imaging ( fMRI ) is a relatively new 
technique for measuring changes in cerebral blood ﬂ  ow. The ﬁ  rst 
fMRI studies, showing functional activation of the occipital cortex by visual stimulation and activation of the motor cortex by ﬁ  nger 
movement, were published in the early 1990s.
(1–3) In the years since

(1–3) In the years since 
then, fMRI has been used to investigate the physiological response to a wide variety of experimental procedures in both normal human subjects and diverse patient groups. In the next 10 years, fMRI will probably establish a role for itself in radiological and psychiatric practice; currently the clinical role of fMRI is limited to specialized applications such as assessment of hemispheric dominance prior to neurosurgery.
(4)
The outstanding advantage of fMRI over alternative methods 
of imaging cerebral blood ﬂ  ow, such as positron emission tomo-
graphy ( PET ) and single-photon emission computed tomography 
(SPECT ), is that it does not involve exposure to radioactivity. This 
means that a single subject can safely be examined by fMRI on

197
many occasions, and that the ethical problems of examining 
patients are minimized. Functional MRI also has superior spatial resolution (in the order of millimetres) and temporal resolution (in the order of seconds) compared with PET and SPECT.
In this chapter, we provide an introduction to technical issues 
relevant to fMRI data acquisition, study design, and analysis. An introduction to the basic physical principles of magnetization and nuclear magnetic resonance, and the technology, is given in Chapter 2.3.7.
Many excellent specialist texts covering all aspects of functional 
magnetic resonance imaging are available for the reader seeking more detailed treatment of the issues.
(5–7)
Cerebral activation and blood-ﬂ  ow changes
Try closing your eyes and then opening them again. At the moment

(5–7)
Try closing your eyes and then opening them again. At the moment 
that you open your eyes, neurones in the occipital cortex that are specialized for the perception of visual stimuli will show a sudden and dramatic increase in their rate of discharge. There is a short delay (approximately 100 ms) between the stimulus and neural response owing to the propagation of electrical activity from the retina via the optic nerves and tracts to the visual cortex. Later, some 3 to 8 s after stimulus onset, there will be an accompanying change in the local blood supply to the stimulated area of cortex. Blood ﬂ  ow increases without a commensurate increase in oxygen 
uptake by the visual cortex, leading to a local increase in the ratio of oxygenated to deoxygenated forms of haemoglobin.
The linkage between neural activity and regional cerebral blood 
ﬂ ow, sometimes called neurovascular coupling, has been known

ﬂ ow, sometimes called neurovascular coupling, has been known 
since Roy and Sherrington ﬁ  rst reported ‘changes in blood supply 
in accordance with local variations of functional activity’ in 1894. However, the biophysical and biochemical mechanisms for neuro-vascular coupling are complex and not yet completely deﬁ  ned 
in detail.
(7)
Endogenous contrast agents
The fact that neural activity is linked to local blood ﬂ  ow provides

in detail.
(7)
The fact that neural activity is linked to local blood ﬂ  ow provides 
the opportunity for functional MRI. The most common, and non-invasive, approach exploits the paramagnetic properties of iron in deoxygenated haemoglobin as an endogenous contrast agent. Neural activity causes a local reduction in the ratio of deoxygenated to oxygenated haemoglobin, so that the paramagnetic effects of deoxyhaemoglobin are ‘diluted’ . Since apparent spin–spin relaxation or dephasing is accelerated by microscopic inhomogeneities in the magnetic ﬁ  eld due to the presence of paramagnetic contrast agents, 
the net effect of diluting deoxyhaemoglobin will be to prolong 
T*2
times in areas of the brain that receive an increased blood ﬂ  ow as a 
consequence of neural activity. The haemodynamic effect on spin–spin relaxation can be measured by a 
T*2-weighted signal change (of 
3 per cent or less) which is blood oxygen level dependent ( BOLD ).

Imaging sequences for fMRI
Several different pulse sequences can be used to collect MRI data 
that are sensitive to functionally determined changes in signal strength. Here we will concentrate on gradient echo sequences which, combined with special techniques for very rapid data acqui-sition, are most widely used to date for fMRI. However, spin echo sequences can also be used for functional MRI data acquisition, 
and gradient echo sequences can be used for structural MRI.
Gradient echo sequence
The basic principle is similar to spin echo imaging. An initial excitation pulse of radiofrequency energy is supplied at the Larmor frequency to the brain in the presence of a powerful static magnetic ﬁ eld. Protons are excited to a state characterized by increased 
transverse magnetization and a coherent phase of precession around the axis of the external ﬁ  eld. Immediately the radiofre-

quency pulse has ceased, protons begin to relax back to their equi-librium state of maximum longitudinal magnetization and random phase of precession, emitting a radiofrequency signal by free induction decay.
In gradient echo imaging, the process of spin–spin relaxation 
(dephasing) is ﬁ  rst accelerated by brieﬂ  y applying a gradient to the 
magnetic ﬁ  eld shortly after the excitation pulse. Then, at some time 
(TE/2) after the excitation pulse, a second gradient is applied to 
reverse the process of dephasing, causing rephasing and a signal maximum or echo some time (TE) after excitation. The sequence is repetitively applied with a constant time interval between con-secutive excitations (TR).
The objective is to manipulate spin–spin relaxation by brief per-
turbations of the external magnetic ﬁ  eld rather than by supplying

turbations of the external magnetic ﬁ  eld rather than by supplying 
additional pulses of radiofrequency energy as in spin echo imaging. Frequency- and phase-encoding gradients are applied to locate the sources of signal in three-dimensional space (see Chapter 2.3.7).
One advantage of gradient echo imaging is that TE and TR can 
both be shorter than in spin echo imaging, allowing an overall reduction in scanning time. However, if TR is short, spoiler gradi-ents or radiofrequency pulses may be needed to ensure that the protons have returned to equilibrium before the next excitation pulse is supplied. The ﬂ  ip angle a induced by radiofrequency exci-
tation can be adjusted to generate images weighted by different sources of tissue contrast. T
1-weighted images are generated by 
radiofrequency pulses causing ﬂ  ip angles of the order of 10 ° to 
20°. For functionally sensitive T2-weighted images, more radiofre-

quency energy must be supplied in the excitation pulse to give a ﬂ  ip 
angle approaching 90 °.
Echoplanar imaging
The gradient echo sequence equivalent to a fast spin echo sequence

The gradient echo sequence equivalent to a fast spin echo sequence 
is obtained by rapidly applying, or blipping, a series of rephasing gradients following the excitation pulse and dephasing gradient. Gradient blipping is done extremely rapidly (<1 ms), and up to 128 echoes can be generated from a single excitation. Clearly, the advantage of such echoplanar imaging is the speed of acquisition. Multislice images of the entire cortex, with slice thickness of only a few millimetres, can be acquired in 2 s or less. Such high-speed imaging is highly desirable for functional MRI, where we wish to detect physiologically determined changes in magnetic resonance signal with the best possible temporal resolution. However, the hardware required for rapid gradient blipping has only become widely available in the last few years.
Artefacts

Artefacts
The main sources of artefact in functional MRI are the same as for structural MRI (see Chapter 2.3.7).2.3.8 functional magnetic resonance imaging

SECTION 2  the scientific basis of psychiatric aetiology 198
Movement
Movement of the subject’s head during fMRI data acquisition is 
inevitable, and attempts to eliminate it by ﬁ  xing the head in the 
scanner may paradoxically exacerbate the problem. The best approach of minimizing movement is to ensure that the subjects are not unduly anxious about the scanning procedure, that they understand clearly what they are being asked to do, and that they are comfortable in the scanner before data acquisition begins. Experiments should be designed so that they do not require the subject to move extensively; small ﬁ  nger movements required for 
button pressing do not generally cause severe head movement. However, even very small movements of the head (less than 1 mm) can cause signiﬁ  cant artefacts in fMRI data.
Involuntary or physiological movements are mostly due to the 
cardiorespiratory cycle causing pulsation of the cerebrospinal ﬂ  uid

cardiorespiratory cycle causing pulsation of the cerebrospinal ﬂ  uid 
and vascular spaces. Therefore, these movements often occur at a 
higher frequency than the frequency of image volume acquisition, 
and are aliased into the signal as a low frequency confound.

The susceptibility artefact is exaggerated by gradient echoplanar imaging, typically causing signal loss in inferior temporal and orbitofrontal brain regions close to bone or sinuses. The problem is further compounded if subjects are asked to speak during scan-ning, since slight deformations of the sinuses associated with overt articulation can cause changes in susceptibility artefact, which can mimic signal changes due to speech-related neural activity. If overt articulation is necessary to monitor the subject’s performance on the experimental task, then it is advisable to design the sequence so that images are not acquired while the subject is speaking.
Hardware
The hardware requirements for functional MRI include a supercon-ducting magnet, a radiofrequency coil, computers, and a purpose-built room, as described in Chapter 2.3.7.

Hardware
Gradient coils
The essential extra prerequisite is gradient coils capable of very rapidly blipping the external magnetic ﬁ  eld for echoplanar imag-
ing. The gradients required are small compared with the external ﬁ eld (1 to 10 mT/m) but may need to be applied for less than 1 ms. 
The speed with which the gradient is switched on, the slew rate, is necessarily fast (up to 200 mT/m/s). Such rapidly changing gradie nts 
can cause eddy currents in the gradient coils, adversely affecting the homogeneity of the ﬁ  eld. This problem is minimized by actively 
shielding the coils, which requires yet another set of coils.
Audiovisual equipment

It must be possible to present visual and auditory stimuli to sub-jects while they are lying with their heads in the bore of the magnet. Headphones are required to clearly present auditory stimuli in the presence of the loud background noise of gradient switching. Visual stimuli can be projected on to a screen, viewed through a periscope. The subject should have access to an alert button. In addition, it is generally useful for subjects to use a button-press device to indicate their response to cognitively demanding experimental tasks. These behavioural data will need to be monitored during scanning.Experimental design
The basic principle of experimental design in fMRI is to manipu-late the subject’s experience or behaviour in some way that is likely to produce a functionally speciﬁ  c neurovascular response. It is

usually important that the experiment should be designed to allow some other measure of response, for instance a button press, to be monitored simultaneously. We shall illustrate these and other principles by considering how one might design an experiment to identify the regions of the brain that are important in making a (semantic) decision about the meaning of words. As will become clear, no single design is ideal; each has its strengths and weaknesses, and the choice between them should also be considered carefully in the light of the particular hypothesis one is using fMRI to test.
Blocked periodic design
This experimental design, in its simplest form, involves alternately presenting the subject with two conditions: an activation (A) con-dition and a baseline (B) condition. Each condition is presented for an identical epoch of time. During each epoch, several stimuli are sequentially presented with an interstimulus interval ( ISI) that

is less than the epoch length. The cycle of alternation between A and B conditions is repeated a number of times over the course of each experiment.
For example, during each 30-s epoch of the A condition, we 
could visually present subjects with a series of 12 common concrete nouns (ISI = 2.5 s) and ask them to decide for each word whether it refers to an animate object (e.g. ‘goat’) or an inanimate object (e.g. ‘bucket’). The subjects could be asked to indicate their deci-sion by pressing one of two buttons: left for living objects and right 
for non-living objects. During each 30-s epoch of the B condition, we could present words at the same rate, but ask subjects to decide 
whether they are written in upper- or lowercase letters. This deci-sion could be monitored by button press as in the A condition. The two epochs could be presented alternately, beginning with the B condition, in ﬁ  ve cycles for a total experimental time of 5 min.

Functional MRI data would be acquired continuously throughout the experiment (
Fig. 2.3.8.1Fig. 2.3.8.1).
The rationale for this design is that the two conditions are 
matched in all respects apart from semantic analysis; words are visually presented at an identical rate, and subjects are asked to signal their decision by an identical device. But while condition A demands semantic analysis of the words (what do they mean?), condition B demands only orthographic analysis (what do they look like?). We assume that only those regions of the brain that are speciﬁ  cally responsible for semantic analysis will show an increased 
magnetic resonance signal during condition A; those regions responsible for visual perception and motor output will be activat-ed identically under both conditions, and so will not demonstrate a periodic signal change at the frequency of AB alternation. This set of assumptions is sometimes referred to as cognitive subtraction.

Blocked periodic designs can generate robust signal changes in 
fMRI, as long as the two conditions are not too closely matched. The drawbacks are that it is impossible to assess the response to a single stimulus and the critical assumption of cognitive subtraction may not always be valid. Sometimes two experimental tasks that appear to differ only in terms of one component process may actually invoke entirely different cognitive strategies and so cause activation of entirely different neurocognitive networks.

199
Parametric design
Parametric designs are so called because the same task is presented 
throughout the experiment but some continuously variable param-
eter of the task is experimentally manipulated. For example, we 
could ask subjects to perform the semantic analysis task for 5 min, 
but continuously vary the interval between consecutive stimuli 
(words) from 10 s at the start of the experiment to 1 s at the end. 
Here we are assuming that as the task becomes more difﬁ  cult, 
i.e. the interstimulus interval becomes shorter, blood ﬂ  ow to the 
regions specialized for semantic analysis will increase. The main 
advantage of this design is that it avoids the assumption of cognitive 
subtraction; the main disadvantage is that it may lack speciﬁ  city. 
Motor and visual cortex, as well as brain regions specialized for 
semantic analysis, will probably show an increased blood ﬂ  ow as 
the rate of stimulus presentation is increased.
Event-related design

Event-related designs are composed of a series of individual stimuli. 
They may be coupled with sequences for very rapid image acquisi-
tion so that the temporal pattern of response to a single event can 
be resolved in detail. An event-related design would be advanta-
geous for our semantic analysis experiment if we were particularly 
interested in correlating some aspect of the behavioural response 
to each stimulus, for instance accuracy of decision or reaction 
time, with the neurovascular response measured using fMRI. A dis-
advantage of such designs is that signal changes induced by a single 
trial are generally weak compared with the 2 to 5 per cent signal 
changes that are typical in blocked periodic experiments.
Beyond a single experiment
Generally, the hypothesis in question demands the investigation

Generally, the hypothesis in question demands the investigation 
of more than a few subjects and/or more than one experimental condition. When designing the studies it is important that ran-
domization should be used appropriately to eliminate confound-
ing effects of the order in which experiments are conducted, and 
of the order in which different subjects are scanned. Practice on a 
task may substantially alter the neurovascular response, and so all 
subjects should receive preliminary training on the task according 
to a standard protocol. If there is considerable variability between 
subjects in their ability to perform a task, consider adjusting the 
difﬁ culty of the task presented in the scanner so that each subject 
is performing at the same level in terms of accuracy or reaction 
time. The use of functional MRI to study longitudinal changes by

time. The use of functional MRI to study longitudinal changes by 
repeated examination of the same subject(s), for instance before 
and after the administration of a drug, will generally improve 
the statistical power to detect the effect of interest by controlling 
for idiosyncratic variability of functional response between 
subjects.
General principles of data analysis are reviewed here; for more 
detailed coverage of the issues and the methods implemented in a 
variety of software packages, see.(5–7)
Movement estimation and correction
The ﬁ  rst step in fMRI data analysis is to estimate the extent of head 
motion during data acquisition and to correct it. Due to the mul-
tislice acquisition protocols generally used for fMRI, the magnetic 
ﬁ eld to which the brain is exposed will change dramatically within 
the space of a few micrometres at the superior and inferior edges of

the space of a few micrometres at the superior and inferior edges of 
a selectively irradiated slice. This means that minute head move-
ments (<1 mm) can have disproportionately large effect on mag-
netic resonance signal.
Head movement occurring at the same time as time as experi-
mental stimuli are present, namely stimulus correlated motion, 
can artefactually exaggerate the neurovascular response. Head 
movement occurring randomly with respect to the experimental 
design is more likely to cause the opposite problem of artefactually 
attenuating the measured response. Therefore it is essential to use a 
computerized method for movement estimation and correction.
Statistical models for the neurovascular response
The next step in analysis is to estimate the strength of the experi-
mentally determined signal change in the time series of magnetic 
resonance signal measurements at each voxel in the image. This

resonance signal measurements at each voxel in the image. This 
requires some sort of model for the response. The simplest model, 
for a blocked periodic design, is a square wave at the same frequen-
cy as the experimental input function. This model assumes that a 
brain region activated speciﬁ  cally by condition A will show an 
immediate increase in signal intensity, which is sustained through-
out the epoch until the onset of condition B. The problem with this 
model is that the increase in magnetic resonance signal during 
condition A is due to changes in blood ﬂ  ow and oxygenation, which 
are dispersed and delayed by several seconds relative to the onset of 
condition A. Furthermore, this haemodynamic delay between 
stimulus onset and measurable response will be variable from one 
voxel to another. Therefore it is important that the experimental

voxel to another. Therefore it is important that the experimental 
effect should be modelled as an increase in signal intensity that 
is arbitrarily delayed relative to the onset of the activating 
stimulus. The most general way of achieving this is to convolve the 
Fig. 2.3.8.1 Design, response, and modelled response for a blocked periodic 
experiment. The experimental design or input function is represented by a square 
wave (solid line), which alternates periodically between a baseline (B) and an 
activation (A) condition. The B condition is presented ﬁ  rst, and the BA cycle is 
repeated ﬁ  ve times in the course of the experiment. Images are acquired every 
3 s during the experiment, and the T*2-weighted signal observed at an activated 
voxel is shown by points joined by a solid line. There is clearly a signal increase

voxel is shown by points joined by a solid line. There is clearly a signal increase 
during the A condition. The modelled response is shown by the broken line.2.3.8 functional magnetic resonance imaging

SECTION 2  the scientific basis of psychiatric aetiology 200
experimental input function (the vector coding changes in experi-
mental conditions) with a model of the haemodynamic response. The haemodynamically convolved input function can then be regressed on the fMRI time series at each voxel to estimate the neu-rovascular response to changing experimental conditions.
In ﬁ tting linear regression models to fMRI time series, one 
important technical issue is that the residuals of the regression will generally not be white noise or serially independent. Rather the residuals will typically have long-range dependency or long memory in time and this will need to be addressed for proper estimation of linear model parameters.
(8) There are probably sev-

eral possible artefactual sources of autocorrelation in fMRI time series residuals—including imperfectly modelled experimental activation, uncorrected head movement, and aliased cardiorespi-ratory pulsation. However, recently attention has focused on the role of low frequency, spatially coherent, endogenous oscillations of large neuronal ensembles as a source of long memory in fMRI time series.
(9) This hypothesis has encouraged studies of the 
univariate and multivariate properties of fMRI data recorded at rest, i.e. in the absence of experimentally controlled task processing.
(10,11)
Activation mapping
The next step in analysis is often to decide which of the several thousand voxels in the image have demonstrated such a strong response to the experiment that it is unlikely to be due to chance. In other words, we want to identify the signiﬁ  cantly activated vox-

els. Let us assume that we have estimated the neurovascular response by the magnitude of a linear model coefﬁ  cient at each and 
every voxel, and refer to this as our test statistic. The problem is then to assign a probability to each test statistic under the null hypothesis that the experiment had no effe ct on the brain.  T o do this 
we need to know the probability distribution of our test statistic under the null hypothesis. There are broadly two ways we can know this distribution: we can work it out from mathematical theory, or we can sample it by randomly permuting the data. Theoretical dis-tributions are quicker to evaluate than permutation distributions, 
but permutation entails many fewer assumptions and is the gold 
standard against which the validity of theoretical approximations should be checked.
Once we have a probability distribution for the test statistic, we 
still have to decide what p-value we wish to adopt as our threshold

still have to decide what p-value we wish to adopt as our threshold 
for activation. If we choose a small (conservative) p-value (e.g. 
<0.00001), only those voxels that demonstrate a very powerful response will be identiﬁ  ed as activated. There will be few false-
positive or type 1 errors, i.e. almost all the voxels we identify as activated will truly be activated. But there will probably be a large number of false-negative or type 2 errors, i.e. many voxels that are truly activated will not be identiﬁ  ed as such. Conversely, if we 
choose a large (lenient) p-value (e.g. <0.01), there will be a larger 
number of false-positive errors but a smaller number of false-negative errors. The choice of p-value should be informed by the 
search volume, or the number of voxels tested for signiﬁ  cance. The 
larger the search volume, the smaller the p-value will need to be for

larger the search volume, the smaller the p-value will need to be for 
an acceptable degree of type 1 error control. A rule of thumb is that thep-value should be approximately the reciprocal of the search 
volume. More elaborate methods have been advocated for correct-ingp-values for large numbers of tests on imaging data.
An alternative approach to testing tens of thousands of voxels 
against a suitably small probability threshold, with an associated risk of major type 2 error, is to combine information about the experi-
mental response over several voxels. For example, we can initially apply a lenient threshold ( p = 0.05) to the test statistics estimated at

mental response over several voxels. For example, we can initially apply a lenient threshold ( p = 0.05) to the test statistics estimated at 
each voxel, and set to zero any voxel that does not have a test statistic greater than the corresponding critical value. The result will be a map of several spatially contiguous clusters, ranging in size from a single voxel to several hundred voxels (Plate 10). We can ascertain the probability distribution for cluster size under the null hypothesis either by theory or permutation. Then we can proceed to identify signiﬁ  cantly activated clusters instead of voxels. The advantage of 
hypothesis testing at cluster level is a greater power to detect signiﬁ  -
cant foci of activation, partly because there will be many fewer clus-ters than voxels to test, so the p-value can be legitimately increased. 
The disadvantage is the loss of spatial resolution of activation.
Multivariate approaches

Many of the ‘higher-order’ cognitive tasks that are likely to be of greatest interest to psychiatric research do not activate a single modular region of the brain. Instead, they typically activate several spatially distinct or distributed regions that together comprise a large-scale neurocognitive network for performance of the task. It may then be of interest to investigate functional integration between different regions or nodes of the network. The simplest way to do this is by estimating the co rrelation betwee n a pair of fMRI 
time series observed at different voxels or regions. Large correla-tions, whether negative or positive, may be described as evidence for functional connectivity. Psychiatric disorders may be character-ized by abnormal functional relationships between coactivated regions, or functional dysconnectivity.
More sophisticated techniques for investigating functional

More sophisticated techniques for investigating functional 
relationships between large numbers of voxels or regions include 
multivariate methods such as principal component analysis, dis-criminant analysis, and path analysis. These methods are equally applicable to structural MRI data, where they may provide indirect evidence for anatomical connectivity between regions.
Within- and between-group analysis
Once a measure or parameter of experimental response has been estimated in each fMRI time series, the resulting parameter maps can be registered in standard space. There are many possible computational algorithms for spatial registration. The most com-monly used at present is an afﬁ  ne transformation, which applies a

global and linear rescaling in three dimensions to each individual image. A commonly adopted standard space is that represented in a stereotactic atlas of the brain originally written by Talairach and T ournoux to assist neurosurgeons in locating subcortical structures.
(12) In these systems, each voxel is assigned a set of { x,y,z}
coordinates which deﬁ  ne its position. In Talairach–T ournoux space, 
the coordinates are deﬁ  ned relative to the cerebral midline and a 
line is drawn between the anterior and posterior commissures (intercommissural or AC–PC line). After registration, parameter maps are usually smoothed by appl ying a two- or  three -dime nsional
Gaussian ﬁ  lter to accommodate variability in sulcogyral anatomy 
between subjects and error in spatial registration.
It is then possible to test a wide variety of hypotheses about the

It is then possible to test a wide variety of hypotheses about the 
response parameters measured over several subjects at each voxel in standard space. For example, one can test the null hypothesis that there is zero mean or median power of experimental response within a group, or the null hypothesis that there is zero difference in the power of response between two groups. It is also possible to

201
test for correlations between the power of functional response and 
some behavioural or symptom measure within a group.
Visualization
The ﬁ  nal result of fMRI data analysis will often be visualized as a 
map in standard space. The background for the map will generally be a grey-scale image of cerebral anatomy, such as a structural MRI dataset with ﬁ  ne spatial resolution and good tissue contrast between 
grey and white matter. In this case, one should beware of the poten-tial discrepancy in geometric distortion between images of the same brain acquired using different sequences.
The background image will often be combined with, or substi-
tuted by, a rectangular grid allowing any feature of interest to be referred directly to the appropriate atlas of standard anatomical space. If the image is displayed as a series of two-dimensional slices, the z coordinate for each slice in standard space should 
also be displayed and the left and right sides of the right clearly indicated.

Voxels or clusters that demonstrate a signiﬁ  cant effect are gener-
ally coloured against the grey-scale background image (Plate 11). A range of colours can be used to encode additional information. For example, the haemodynamic delay of response at each generically activated voxel may be colour coded by a continuous spectrum. Other strategies for visualization include use of three-dimensional rendering to show foci of activation in the context of the sulcogyral anatomy of a whole hemisphere, and ‘ﬂ  at mapping’ whereby the 
template image is deformed to a smooth sphere and then mapped to a plane before activation foci are superimposed on it.
Comprehensive background information on fMRI 
physiology, experimental design, and data analysis:
Jezzard, P ., Matthews, P .M., and Smith, S.M. (eds) (2003). Functional 
magnetic resonance imaging: an introduction to methods . (2nd edn)

magnetic resonance imaging: an introduction to methods . (2nd edn) 
The physiological origins of the BOLD effect:
Logothetis, N.K., Pauls, J., Augath, M.A., et al. (2001). Neurophysiological 
investigation of the basis of the fMRI signal. Nature ,412,
150–7.
Current perspectives of fMRI applications:
Matthews, P .M., Honey, G.D., and Bullmore, E.T. (2006). Applications of 
fMRI in translational medicine and clinical practice. Nature Reviews. 
Neuroscience ,7, 732–44.
Community web site for information about Brain Mapping and methods: 
www.brainmapping.org
1. Kwong, K.K., Belliveau, J.W., Chesler, D.A., et al. (1992). Dynamic 
magnetic resonance imaging of human brain activity during primary sensory stimulation. Proceedings of the National Academy of Sciences of 
the United States of America ,89, 5675–9.

2. Stehling, M.K., Turner, R., and Mansﬁ  eld, P . (1991). Echo-planar 
imaging: magnetic resonance imaging in a fraction of a second. Science ,
254, 43–50.
3. Le Bihan, D. and Karni, A. (1995). Applications of magnetic resonance 
imaging to the study of human brain function. Current Biology ,5, 231–7. 4. Matthews, P .M., Honey, G.D., and Bullmore, E.T. (2006). Applications 
of fMRI in translational medicine and clinical practice. Nature Reviews 
 5. Jezzard, P ., Matthews, P .M., and Smith S. (2001). Functional magnetic 
resonance imaging: an introduction to methods . Oxford University Press, 
Oxford.
 6. Frackowiak, R.S.J., Ashburner, J.T., Penny, W.D., et al. (2002). Human 
brain function . Academic Press, San Diego.

Oxford.
 7. Buxton, R.B. (2002). An introduction to functional magnetic resonance 
imaging: principles and techniques . Cambridge University Press, 
 8. Maxim, V ., Sendur, L., Fadili, J., et al. (2005). Fractional Gaussian 
noise, functional MRI and Alzheimer’s disease. NeuroImage ,25,
141–58.
 9. Leopold, D.A., Murayama, Y., and Logothetis, N.K. (2003). Very 
slow activity ﬂ  uctuations in monkey visual cortex: implications for 
functional brain imaging. Cerebral Cortex ,13, 422–33.
10. Greicius, M.D., Krasnow, B., Reiss, A.L., et al. (2003). Functional 
connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the 
United States of America ,101, 4637–42.
11. Achard, S., Salvador, R., Whitcher, B., et al. (2006). A resilient,

11. Achard, S., Salvador, R., Whitcher, B., et al. (2006). A resilient, 
low-frequency, small-world human brain functional network with 
highly connected association cortical hubs. The Journal of Neuroscience ,
26, 63–72.
12. Talairach, J. and T ournoux, P . (1988). Co-planar stereotaxic atlas of the 
human brain . Thieme, Stuttgart.
2.3.9 Neuronal networks, epilepsy, 
and other brain dysfunctions
The dynamics of highly interconnected networks of neurones 
are fundamental to both normal and pathological functioning of the brain.
(1, 2) Epilepsy is perhaps the most dramatic example of a 
dysfunctional neuronal network,(3) characterized by intense and 
highly synchronous neuronal activity, but more subtle dysfunction is associated with other conditions, such as schizophrenia.
(4)
This chapter will largely focus on the hippocampus, and to a

(4)
This chapter will largely focus on the hippocampus, and to a 
lesser degree on the neocortex. The hippocampal formation is implicated in several important psychiatric and neurological prob-lems. The hippocampus and amygdala are often the site of epileptic foci, which can lead to problems in learning and memory, emotion, anxiety, and other problems. This kind of epilepsy is variously known as temporal lobe epilepsy, complex partial seizures, or lim-bic epilepsy. The hippocampus and associated limbic areas have been linked both to affective disorders and to psychoses. This chap-ter will consider the cellular organization of the hippocampus and then outline aspects of the emergent properties of neuronal net-works in the hippocampus and speculative role in psychiatric dis-
orders. Cellular and network mechanisms of focal epilepsy, and

orders. Cellular and network mechanisms of focal epilepsy, and 
learning impairments associated with limbic epilepsy will be reviewed.2.3.9 neuronal networks, epilepsy, and other brain dysfunctions

SECTION 2  the scientific basis of psychiatric aetiology 202
Hippocampal organization
Anatomy
The hippocampus resembles the neocortex in containing a major-
ity of excitatory neurones, the pyramidal cells, and granule cells, 
which use glutamate as their neurotransmitter (E in Fig. 2.3.9.1).(1, 2)
Most of the remaining 10–20 per cent of neurones in the hippo-
campus are inhibitory, and use γ-aminobutyric acid (GABA) as 
their neurotransmitter (I in Fig. 2.3.9.1). The inhibitory neurones 
fall into several distinct subtypes according to where their axons 
go (and hence which cells they inhibit), where their cell bodies are, 
the shapes of their dendrites, whether they contain more than 
one transmitter, and whether they contain particular calcium-
binding proteins. This chapter will ignore most of the diversity of 
interneurones.(5)
There are many more excitatory pyramidal cells (E and triangles) 
than inhibitory interneurones (I and circles). As with most neu-

rones, they receive inputs onto their dendrites and somata (the latter 
contain the nucleus and are represented by a triangle or circle). The 
level of simpliﬁ  cation is clear from the observation that each 
pyramidal cell receives tens of thousands of synapses. Axons from 
other regions, known as afferents, make excitatory synapses (e) 
with both pyramidal cells and interneurones. Most of the interneu-
rones make inhibitory synapses (i) onto pyramidal cells. The inhi-
bition of the pyramidal cell is called ‘feed-forward’ (f.f.) when the 
interneurones were excited by afferent axons and ‘feed-back’ (f.b.) 
when they were excited by pyramidal cells. Interneurones also 
inhibit each other forming a mutually inhibitory network (m.i.); 
this network is important in some kinds of physiological network

this network is important in some kinds of physiological network 
oscillation (see text). Finally, pyramidal cells make excitatory syn-
apses onto each other (r.e.), which can lead to epileptic discharges 
if not held in check by inhibitory mechanisms.
Evoked responses
Each hippocampal (or neocortical) area receives ‘afferent’ synaptic 
inputs from other areas. Most afferents are excitatory; stimulating 
them provides a convenient tool to study the operation of the neu-
ronal circuits involved. The responses evoked in hippocampal neu-
rones typically start with an excitatory postsynaptic potential. If 
the excitatory postsynaptic potential is strong enough, it will result 
in an action potential triggered at a low-threshold zone near the

in an action potential triggered at a low-threshold zone near the 
cell body, probably a short distance down the axon. The excitatory postsynaptic potential is followed by a fast and a slow inhibitory 
postsynaptic potential. Both the fast inhibitory and excitatory post-
synaptic potentials are due to ligand-gated channels where the 
transmitter receptor is part of the same molecular structure as the 
ion channel. In the case of inhibition this is the GABAA receptor, 
which allows chloride ions to pass. In the case of excitation it is a 
variety of glutamate receptors, which are permeable to sodium, 
potassium, and in some cases calcium ions, and which are further 
subdivided into α-amino-3-hydroxy-5-methyl-4-isoxazolepropi-
onic acid (AMPA)/kainic acid, N-methyl- d-aspartate (NMDA) and 
other classes. The slow inhibitory postsynaptic potential is due to

other classes. The slow inhibitory postsynaptic potential is due to 
GABAB receptors, which are G protein coupled and use second 
messengers to open separate potassium channels. Many other kinds 
of G-protein couple receptors exist, and often are involved in mod-
ulating neuronal excitability or synaptic function.
Inhibitory neurones can be triggered both by activity in the 
principal cells (pyramidal or granule), resulting in recurrent or 
feedback inhibition, and directly by the incoming afferents, result-
ing in feed-forward inhibition. Experimentally, the synchrony of 
the stimulation of the afferent input imposes synchrony on the 
response with the useful consequence that the extracellular cur-
rents generated by the activity of individual pyramidal or granule 
cells can summate (because the cells are located in tight layers) and

cells can summate (because the cells are located in tight layers) and 
produce large ‘ﬁ  eld potentials’ comprising a population excitatory 
postsynaptic potential, followed by a population spike.
Field potentials evoked by local stimulation are over in 10 to 
20 ms and the slowest intracellular components end within a few 
100 ms to 1 s. However, stimulation can have much more prolonged 
effects. The best known of these is long-term potentiation, in which 
a brief train of stimuli can result in an increase, lasting hours 
or days, in the response to a ﬁ  xed test stimulus. The modest condi-
tioning event and the enduring consequence make long-term 
potentiation an attractive model of learning and memory, although 
the evidence that it really is the direct cellular substrate for learning 
remains circumstantial.(6) It is perhaps more likely that long-term

remains circumstantial.(6) It is perhaps more likely that long-term 
potentiation provides an artiﬁ  cial experimental tool that depends 
on cellular and molecular mechanisms that may also be involved in 
learning and/or other plastic changes in synaptic strength.
Local circuits
Hippocampal neurones are not just arranged as a simple synaptic 
relay where afferents excite target cells to produce an output 
depending on the size of the input and the state of inhibition at 
that time. Instead there exists a complex synaptic network, or local 
circuit, interlinking neurones of all kinds (Fig. 2.3.9.1 gives a very 
much simpliﬁ  ed illustration of some of the salient features of 
hippocampal local circuits). This chapter considers two kinds of 
emergent network activity that arise from this organization: focal 
epilepsy and gamma rhythms.
Experimental approaches

Unravelling the cellular and network mechanisms of emergent net-
work phenomena depends on a combination of electrophysiology, 
pharmacology, anatomy, and realistic computer simulations.(2,7)
Two practical issues may need a brief introduction.
Brain slices  have played a pivotal role in developing theories 
on the operation of neuronal networks. Slices about 0.4 mm thick 
are cut from the brains of deeply anaesthetized or recently killed 
experimental animals, or sometimes from humans undergoing 
 Fig. 2.3.9.1 Schematic illustration of hippocampal neuronal network.

203
neurosurgery. Brain slices can survive many hours in vitro  in an 
artiﬁ cial cerebrospinal ﬂ  uid, usually equilibrated with 95 per cent 
oxygen and 5 per cent carbon dioxide (with bicarbonate providing a pH buffer). If the slices are prepared under sterile conditions, they can survive for weeks as ‘organotypic slice cultures’ . In both cases the visualization of the anatomy of the living slice helps locate electrodes, the mechanical stability greatly simpliﬁ  es recordings 
from inside neurones, and the lack of a blood–brain barrier facili-tates drug applications and changes in ion concentrations. Brain slices have proved immensely popular and successful, but it is important to remember that they are only one tool in the armoury needed to study brain function, and that ultimately results from them must be put in the context of the whole organism.
Realistic computer simulations  provide the means to determine

Realistic computer simulations  provide the means to determine 
whether what we know at one level, for instance of the properties of individual neurones and their interconnections, are necessary and sufﬁ cient to explain the emergent properties at the next level, here 
of circuits of a few thousand neurones. The most useful models for this purpose are tightly constrained by experimental data, and ide-ally are used to make experimentally testable predictions. Mostly they consist of several ‘compartments’ to represent the anatomy of the neurone’s dendrites and soma. Each compartment consists of several differential equations representing speciﬁ  c ion channels, 
which may be gated by membrane potential, extracellular neuro-transmitters, or intracellular calcium. Large number of neurones can then be wired together in larger-scale simulations, using biologi-cally realistic anatomical connectivity and synaptic properties.
(2,7)
Emergent properties of hippocampal 
networks

(2,7)
networks
Hippocampal rhythms
The organization of hippocampal networks (Fig. 2.3.9.1) leads to 
several distinct kinds of oscillation, which can be considered as ‘emergent’ properties of the network. Perhaps the most prominent rhythm in the hippocampus is theta (3–7 Hz), which, at least in rats, is associated with spatial navigation,
(8) and may play a role in 
memory.(9) Theta results from interactions of the hippocampus 
with two other limbic structures, the septum and the entorhinal cortex. Often superimposed on theta is a faster rhythm known as gamma (30–100 Hz). The best evidence we have now is that gamma is generated by local circuits in the hippocampus and that inhibitory neurones play a crucial role.
(2) The role of gamma in the hippoc-
ampus remains unclear; in the neocortex it has been implicated in higher cognitive processes such as the ‘binding’ of individual sen-sory features into coherent perceived objects.
(10)

(10)
Networks for gamma rhythms
The ﬁ  rst strong clue that inhibitory neurones played a central role 
in gamma rhythms came from hippocampal and neocortical slices in which fast excitatory postsynaptic potentials had been blocked by drugs. Excitation by pulses of glutamate or agonist drugs acting at metabotropic (i.e. G-protein-coupled) glutamate receptors resulted in rhythmic inhibitory postsynaptic potentials in the 
gamma frequency band. A series of experimental tests of predic-
tions from realistic computer simulations showed that this gamma rhythm was generated by the mutual inhibition of inhibitory neurones, which produced a synchronous interruption of the fast discharge the metabotropic glutamate receptor activation would otherwise have evoked. These interruptions lasted for a time, of the

order of 25 ms, that depended on the time course of the inhibitory postsynaptic potentials in interneurones. We named this phenom-enon ‘interneuronal network gamma’ .
During interneuronal network gamma pyramidal cells generate 
rhythmic inhibitory postsynaptic potentials, but do not reach threshold unless they are driven by some other input. Another kind of gamma rhythm occurs when slices are exposed to cholinergic drugs such as carbachol, and/or to non-desensitizing glutamate agonist drugs such as kainic acid. Here each pyramidal cell ﬁ  res on 
some cycles of the rhythm,
(11, 12) so that on average some ﬂ  uctuat-
ing fraction of pyramidal cells ﬁ  res on each cycle. This is closer to 
the situation in vivo .(13)
Signiﬁ  cance of fast coherent 
cortical oscillations
Rhythms such as gamma have been linked with sensory processing

Rhythms such as gamma have been linked with sensory processing 
and with perception and other cognitive functions. They may be disrupted in people with some degree of cognitive impairment, for instance normal age-related cognitive decline,
(14) or there may be a 
more general disruption of cortical rhythms in more severe condi-tions such as schizophrenia.
(4) The complexity of the circuits 
responsible for cortical oscillations means that individuals with apparently normal number of neurones and neuronal organization may still have rather subtle changes on their synaptic networks that can have profound effects on collective oscillations and behaviour.
Gamma rhythms are intimately linked with epilepsy. Coherent

Gamma rhythms are intimately linked with epilepsy. Coherent 
neural activity at gamma frequencies is associated with some kinds of epileptic activity. Gamma rhythms are disrupted in at least one chronic model of epilepsy associated with learning impairments. Finally, the ideas behind the synaptic network mechanisms of the two kinds of phenomena have much in common.
Epilepsy—an emergent property of 
neuronal networks
Epileptic discharges typically involve excessively synchronous activ-

ity in principal neurones. In experimental focal epilepsy this exces-sive synchronization is due to the mutual excitation of pyramidal cells in the hippocampus, neocortex, or related areas. The essential idea is of a chain reaction. Areas that are especially prone to epilep-tic discharges have strong synaptic interconnections between their principal cells (e.g. the pyramidal cells of the CA3 region of the hippocampus or layers 3 and 5 of the neocortex). Activity in a few pyramidal cells can propagate through the synaptic network to recruit the whole population of neurones. Normally this propaga-tion is held in check by inhibitory neurones; if the control mecha-nism is ineffective then epileptic discharges result. In experimental models the balance of synchronization versus control is compro-mised by treatments that weaken inhibition (usually by drugs such

as bicuculline or picrotoxin), strengthen excitation (incubating 
brain slices in solutions lacking magnesium io ns) or strengthen syn-
aptic potentials in general (4-aminopyrid ine). Combined experi-
mental and theoretical studies of such models have led to some general principles.
(7) Synchronous epileptic discharges will result 
under the following conditions.
1 Connections between excitatory neurones are divergent, that is 
each connects to more than one postsynaptic excitatory neurone.2.3.9 neuronal networks, epilepsy, and other brain dysfunctions

SECTION 2  the scientific basis of psychiatric aetiology 204
2 Connections between excitatory neurones are powerful enough 
to make their postsynaptic cells ﬁ  re with a high probability. 
Precisely how high a probability can be depends on factors such as the connectivity and size of the network. The ‘intrinsic’ electrical properties of the neurones are important. Many epilep-sy-prone areas have cells with prominent voltage-sensitive calci-um currents, which are more prolonged than the classical volt-age-sensitive sodium currents of the axonal action potential, and which cause neurones to ﬁ  re bursts of fast sodium action poten-
tials. Such intrinsic bursts greatly amplify transmission between pyramidal cells.
3 The network is large enough to allow all the neurones to link

3 The network is large enough to allow all the neurones to link 
together. The critical mass for a network where the probability of any two cells being directly connected is 1 per cent, and the probability of one cell exciting its target cells is approximately 50 per cent, works out at about 1000 to 2000 neurones.
These features explain experimental brief epileptic discharges 
very effectively. The brain contains inhibitory mechanisms, both synaptic (inhibitory postsynaptic potentials, presynaptic inhibition) and intrinsic (voltage- and calcium-sensitive potassium channels), to terminate hypersynchronous discharges. Other mechanisms are needed to overcome the burst-termination mechanisms for the crucial transition to full-blown seizures lasting tens of seconds to minutes. These include slower synaptic mechanisms (both N-methyl- d-aspartate and metabotropic glutamate receptors,

GABA, which paradoxically can become depolarizing if present in excess), non-synaptic mechanisms (potassium accumulation, electric ﬁ  elds), and abnormal activity arising in axons (ectopic 
spikes, gap junctions).
Convulsant drugs can trigger seizures in normal brains. People 
with epilepsy have a reduced seizure threshold that means they have seizures without an obvious triggering chemical or event. The reasons are far from clear, but may include ab normalities in intrinsic 
properties of neurones or in the connectivity of the neurones. Improvements in non-invasive imaging and in neuropathology 
increasingly reveal misplaced neurones and other more or less 
subtle anatomical malformations in many focal epilepsies, which suggests that the local circuitry is disturbed.
Other kinds of epilepsy have very different mechanisms. Absence

Other kinds of epilepsy have very different mechanisms. Absence 
epilepsy is the other major class where cellular mechanisms are relatively well understood. They involve the interaction of the thalamus and neocortex, although the received wisdom on the underlying mechanism has recently been challenged by experi-ments on one of the key animal models of absence epilepsy.
(15)
Epilepsy—learning and memory

(15)
Patients with temporal lobe epilepsy can have problems with learn-ing and memory. Antiepileptic drugs can have marked side effects, but the observation that chronic animal models of temporal lobe epilepsy also have impairments in learning and memory suggests that this is not the only cause. Memory impairments could result from gross damage, such as hippocampal sclerosis. Gross hippoc-ampal pathology will have effects similar to experimental lesions of the hippocampus, but the observation that at least some of the chronic animal models lack gross hippocampal pathology does not support neuronal death as being the sole cause of impaired learn-ing and memory.At least two chronic experimental epilepsies have either limited

or no cell loss during their induction. These are kindling and ster-eotaxic injection of a minute dose of tetanus toxin. The tetanus toxin model results in a well-characterized and enduring impair-ment of learning and memory, which outlasts the active epileptic syndrome in all except a few rats that show relapse. The absence of medication and of gross cell loss suggest that the psychological impairments in this model have some functional cause. Long-term potentiation remains intact, at least over a period of up to an hour. There is an association of learning impairment with the size of population spikes recorded from the same rats in vivo  and under 
anaesthesia. Inhibition remains impaired in rats at a stage (>3 months after injection) when they had gained remission from epi-leptic seizures, but retained learning impairments.
(16,17)

(16,17)
Abnormalities of the cellular electrophysiology of the postepilep-tic phase can lead to disruption of network properties, including gamma rhythms, which may, in time, provide a link to the behav-ioural problem.
Humans with limbic epilepsy often do have substantial hippoc-
ampal damage, and this will contribute to learning impairments. The experimental evidence suggests that even in the absence of gross hippocampal damage learning impairments can arise as a result of functional disruption of the hippocampal network.

Understanding the operation of networks of neurones provides valuable insight into a range of neurological and psychiatric dis-eases. The role of synaptic networks of excitatory neurones in focal epilepsies is now well established. The ways in which brief epileptic discharges transform into events lasting as long as full seizures are starting to be clariﬁ  ed, and may offer new avenues for developing 
rational therapies. New ideas on the generation of physiological rhythms suggest novel models of psychiatric and neurological problems ranging from impairments in learning and memory in limbic epilepsies to (more speculatively) the disruption of sensory perception in psychoses. Real clinical cases will inevitably be much more complex, but the ideas and models outlined above will aid the understanding of the underlying mechanisms.
Traub, R.D., Jefferys, J.G.R., and Whittington, M.A. (1999). Fast

Traub, R.D., Jefferys, J.G.R., and Whittington, M.A. (1999). Fast 
oscillations in cortical circuits . The MIT Press, Cambridge, MA 
(ISBN 0-262-20118-6).
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T.A. Pedley, J. Aicardi, et al. ). Lippincott, Williams & Wilkins, 
Philadelphia (ISBN 978-0781757775).
Winterer, G. and Weinberger, D.R. (2003). Cortical signal-to-noise ratio: 
insight into the pathophysiology and genetics of schizophrenia. Clinical
Neuroscience Research ,3, 55–66.
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2.3.10 Psychoneuroimmunology
Mind-body literature, in the form of magazines and self-help books 
on stress and healing, is full of deﬁ  nitive claims for the existence of 
powerful inﬂ  uences of emotions and psychosocial stressors on the 
immune system, leading to onset or progression of cancers or infectious diseases. This literature often makes explicit reference to research in psychoneuroimmunology to support these claims. Psychoneuroimmunology is a multi-disciplinary ﬁ  eld that has 
grown rapidly during the last three decades at the crossroads of immunology, behavioural neurosciences, neuroendocrinology, and

grown rapidly during the last three decades at the crossroads of immunology, behavioural neurosciences, neuroendocrinology, and 
psychology. It studies mechanisms and functional aspects of bidi-rectional relationships between the brain and the immune system. Although still controversial, there is evidence that psychological events including emotions can and do inﬂ  uence the outcome of 
infectious, autoimmune, and neoplastic diseases via modulation of cells of the immune system. A surprising ﬁ  nding has been that

infectious, autoimmune, and neoplastic diseases via modulation of cells of the immune system. A surprising ﬁ  nding has been that 
immune events occurring in the periphery also affect mood, behav-iour, and metabolism by modulating brain functions, thereby pro-viding a biologically important link between the immune system and brain. The original discovery that activation of the innate immune system in the periphery causes clinical signs of sickness that are processed in the brain is now being extended to the involve-ment of the immune system in depressive disorders. This new information has solidiﬁ  ed the idea that neurotransmitters, neuro-
peptides, neural pathways, and immune-derived signals such as cytokines are the minimal essential elements that permit the immune system and brain to communicate with one another. These new data offer the unexpected conclusion that the immune 
system is likely to be involved in not only how emotions affect

system is likely to be involved in not only how emotions affect 
health but also how immune events regulate the development and expression of emotions.
Brain inﬂ  uences on immunity
Early investigations
The concept that stressors can have a negative impact on immunity 
and ultimately induce a reduction in host resistance to infectious pathogens and even to tumour progression is not new. As a follow-up of the early studies of Hans Selye on stress, several scientists demonstrated in the 1950s and 1960s that laboratory rodents exposed to various stressors, including inescapable painful electric shocks, displayed an altered resistance to viral, bacterial, and para-sitic infections. These effects of stressors were accompanied by decreases in antibody responses to the speciﬁ  c microbial pathogen

under study. In view of the already demonstrated immunosuppres-sive effects of glucocorticoids and the pivotal role of glucocorti-coids in the stress response, pathophysiological mechanisms of the immunosuppressive effects of stressors were easy to determine. However, it was already clear at that time that mechanisms of the 
effects of stressors on immunity were not that simple since decreas-
es as well as increases in immunity could be observed, depending on the immune response under study, the type of stressor and the time point at which the stressor took place during the mounting of the immune response. Furthermore, administration of glucocorti-coids at physiological instead of pharmacological doses had little effect on some aspects of immunity and evolution of the disease process.
There was little innovation in this ﬁ  eld until the 1980s when a

There was little innovation in this ﬁ  eld until the 1980s when a 
few pioneer immunologists and neuroscientists decided to work together in order to understand how the central nervous system communicates with the immune system. One impetus for this was the demonstration that immune responses can be submitted to Pavlovian conditioning in apparently the same way as the salivary response, as discovered by Robert Ader at the University of Rochester.
(1) Mice exposed to a new taste paired with an immuno-
suppressive agent such as cyclophosphamide during the develop-ment of an antibody response were found to display further decreases in antibody titres when re-exposed to the taste alone in 2.3.10  psychoneuroimmunology

SECTION 2  the scientific basis of psychiatric aetiology 206
the absence of any immunomodulating agent. For this to occur, 
there must be pathways of communication from the brain to the immune system that are activated by the taste paired with cyclo-phosphamide. The search for these pathways of communication resulted in the demonstration of innervation of the primary (thy-mus) and secondary (spleen and lymphoid nodes) lymphoid organs by the sympathetic nervous system.
(2) Sympathetic efferent 
nerves enter lymphoid organs with the vasculature but ultimately separate from blood vessels to innervate the parenchyma, where both B and T lymphocytes reside and can proliferate. Sympathetic ﬁ bres innervating lymphoid organs contain all the neurotransmit-

ter machinery of other sympathetic neurones, including noradren-aline and neuropeptides such as substance P , neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP). This implies that the chemical composition of the microenvironment in which lympho-cytes are present ultimately depends on activity of the autonomic nervous system. These ﬁ  ndings gained in prominence when it was 
discovered that speciﬁ  c subsets of leukocytes have receptors for 
these neuronal communication signals.
Receptors within the immune system

In addition to cytoplasmic receptors that bind steroid hormones including glucocorticoids and sex hormones, lymphocytes, and other cells of the immune system have been found to have mem-brane receptors that bind and respond to most neurotransmitters and neuropeptides and are quasi-identical to brain neurotransmit-ter and neuropeptide receptors. As supported by an important body of literature, activation of these receptors in leukocytes has functional consequences on immune responses whether immunity is measured in vivo or in vitro.
(3) As an typical example, growth 
hormone (GH), a pituitary hormone known for its growth-promoting activity and with no known immune function, was shown to restore the resistance of hypophysectomized rats to an infection with Salmonella typhimurium , with an efﬁ  cacy compara-

ble to that of a tetracycline antibiotic or the macrophage-stimulatingfactor interferon-gamma (IFN- γ).
(4,5) These results obtained in 
vivo were replicated in vitro.(6) GH activated highly puriﬁ  ed popu-
lations of pulmonary macrophages in the same way as IFN- γ. Both 
factors were able to prime macrophages triggered with opsonized zymosan to secrete superoxide anion O
−2, an index of macrophage 
activation, even if GH was less active in this system than IFN- γ.
Antibody blocking studies demonstrated that the priming activity of GH was independent of IFN- γ, and vice versa the activity of 
IFN- γ was distinct from that of GH. This priming had functional 
consequences since both IFN- γ and GH increased the capability of 
macrophages to kill Pasteurella multocida . Since most of the effects

macrophages to kill Pasteurella multocida . Since most of the effects 
of GH on its target cells are mediated by the local production of insulin-growth factors (IGF), the capability of IGF-I to prime alveolar macrophages in vitro was also tested and found to be similar to that of GH, although the priming effects of GH were independent of the local production of IGF-I.
(7) Other studies were 
showing at the same time that non-stimulated as well as immune-activated leukocytes were able to produce a GH-like peptide that was identical to pituitary GH,
(8) conferring credibility to the 
important hypothesis that communication signals originally iden-tiﬁ ed in the neuroendocrine system can actually be used by immune

important hypothesis that communication signals originally iden-tiﬁ ed in the neuroendocrine system can actually be used by immune 
cells. In the same vein, corticotropin-releasing hormone (CRH), the main regulator of the hypothalamic–pituitary–adrenal axis, has been identiﬁ  ed in the immune system in which it functions as an autocrine/paracrine mediator of inﬂ  ammation.
(9) In particular, 
CRH causes degranulation of mast cells and the release of histamine and several proinﬂ  ammatory mediators.
The neuropeptides that are contained in sympathetic nerve 
endings that innervate lymphoid organs can play an important role in the modulation of the ﬁ  ne balance between the different popula-
tions of T helper (Th) cells that regulate cellular and humoral immunity. Th1 cells normally produce IFN- γ and interleukin-2

tions of T helper (Th) cells that regulate cellular and humoral immunity. Th1 cells normally produce IFN- γ and interleukin-2 
(IL-2), and both promote cellular immunity. In contrast, Th2 cells normally produce IL-4 and IL-10 that down-regulate cellular immunity and promote humoral immunity. CGRP and NPY drive Th1 cells towards the production of IL-4 whereas Th2 cells are driven by somatostatin and CGRP to produce IL-2 and IFN- γ.
(10)
If these effects that were observed in vitro are also true under in 
vivo conditions, they provide a possible mechanism by which stress can polarize immune responses in the direction of either Th1 or Th2 cells.
A recent potentially important discovery is that of the inhibition 
exerted by the parasympathetic nervous system on the production of proinﬂ  ammatory cytokines by macrophages. Direct electrical 
stimulation of the peripheral vagus nerve that innervates the liver inhibited the production of proinﬂ  ammatory cytokines by Kupffer

stimulation of the peripheral vagus nerve that innervates the liver inhibited the production of proinﬂ  ammatory cytokines by Kupffer 
cells in response to a lethal dose of endotoxin and prevented devel-opment of septic shock.
(11) This vagal function was termed the 
cholinergic anti-inﬂ  ammatory pathway(12) and it is mediated by 
nicotinic acetylcholine receptors containing an alpha-7 subunit.
Neural inﬂ  uences on the immune system
Since the immune system makes use of communication signals 
and receptors that are identical to those used by the central nervous system, the immune system should be very sensitive to neural inﬂ  u-
ences. Besides the cholinergic anti-inﬂ  ammatory pathway already 
mentioned, many data attest to the fact that brain events have an impact on immune responses. For instance, lesions in the neuro-endocrine brain have profound inﬂ  uences on immunity. As an

mentioned, many data attest to the fact that brain events have an impact on immune responses. For instance, lesions in the neuro-endocrine brain have profound inﬂ  uences on immunity. As an 
example, destruction of the tubero-infandibular region of the hypothalamus in mice persistently abrogates natural killer cell cytotoxic activity without altering T and B cell populations, but cortical and sham lesions had only a short-lived effect.
(13) In other 
studies, ablation of the left sensori-motor cortex decreased cellular immunity whereas ablation of the right sensory-motor cortex increased it, showing that brain inﬂ  uences on immunity are lateral-
ized.
(14) This lateralization phenomenon was later demonstrated to 
exist in the absence of any lesion since left-handed mice, labelled as such based on their predominant use of the left paw to reach a food pellet in a tube that only enabled them to use one paw, displayed higher cellular immune responses than right-handed mice.
(15) The

(15) The 
mechanisms for this lateralized inﬂ  uence of the brain on immunity 
are still elusive.
The impact of stressors on immune responses represents another 
example of the inﬂ  uence of brain events on immunity. At the time 
these studies were carried out it was already well known that the inﬂ uence of psychosocial stressors on the hypothalamic–pituitary–
adrenal axis are not simply a function of the intensity and duration of the stressors but also depend upon their psychological features. Novelty, predictability, and controllability are the key factors that ultimately determine the neuroendocrine impact of stressors. It was therefore not surprising that the same psychological features were pivotal in the inﬂ  uence of stress on immunity. For instance,

207
rats exposed to inescapable electric shocks 24 h after injection of 
syngenic tumour cells displayed more rapid tumour growth and a higher mortality rate than rats exposed to controllable electric shocks, despite the fact that the intensity and duration of electric shocks were exactly the same in both groups.
(16) Lack of control 
had the same inﬂ  uence on the rejection of non-syngenic tumours(17)
and cellular immunity as measured by the proliferative response of 
lymphocytes to T-cell mitogens.(18) It cannot be inferred that 
uncontrollability is always immunosuppressive. Lack of control over the occurrence of electric shocks was later found to increase rather than decrease humoral immunity, as measured by antibody titres against sheep red blood cells injected into rats that were sub-mitted chronically to controllable or uncontrollable electric shocks.
(19) The same difference in the way the immune system 
responds to an uncontrollable stressor was conﬁ  rmed in an experi-

ment in which mice were exposed to the odour of a stressed conge-ner. A 24 h exposure to this stressor decreased the cellular immune response, as measured by proliferation of T cells to mitogens and natural killer cell cytotoxicity, but increased antibody titres against keyhole limpet haemocyanin.
(20)
Stress and the immune system
Studies of the inﬂ  uence of stress on the immune system have also 
been carried out in human subjects in experimental settings or in real-life conditions. In these studies, the immune end points are either measured on blood lymphocytes or deduced from the result of an already existing pathological process. The group of Janice Kiecolt-Glaser at Ohio State University in Columbus is certainly the pioneer in this ﬁ  eld. For instance, ﬁ  rst year medical

students were shown to display a reduction in the production of IFN- γ by circulating leukocytes and a reduced cytotoxicity 
of natural killer cells during the end of the year examination period, and these changes were independent on lifestyles.
(21) As a 
result of extensive studies on different populations at risk, such as spouses experiencing marital conﬂ  ict, caregivers of patients with 
Alzheimer’s disease, and aged subjects, Kiecolt-Glaser’s group pro-posed that negative emotions and stressful experiences can con-tribute to prolonged infection and delayed wound healing. In addi-tion, negative emotions were proposed to directly produce the production of proinﬂ  ammatory cytokines and therefore increase 
the risk for a spectrum of conditions associated with ageing, includ-ing cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, frailty and functional decline, and periodontal disease.
(22)

(22)
The inﬂ  uence of stressful life events on immune responses also 
appear to be modulated by coping strategies, as exempliﬁ  ed by a 
study carried out on susceptibility to upper respiratory tract illness in an adult population sample.
(23) In a little less than 30 per cent of 
a population sample of adults between 18 and 65 years of age, the occurrence of clinical episodes of upper respiratory tract illness over a 15-week period was more frequent in those individuals who experienced high life event stress both before and during the study period. The impact of life events was buffered by an avoidance coping style.
In accordance with the hypothesis that negative emotions nega-
tively impact the immune system, major depressive disorders were initially thought to be associated with depressed immune responses. This association has been conﬁ  rmed for the number of circulating

lymphocytes, proliferative response of lymphocytes to non-speciﬁ  c mitogens, and natural killer cell cytotoxicity.
(24,25) However, more 
recent studies have revealed signs of activation of the innate immune system in at least some forms of depression.
(25,26)
Although most of the literature deals with the inﬂ  uence of stress-
ors and negative emotions, positive emotions have also been studied in their relation to immune events. In graduate students vaccinated against hepatitis B, dispositional positive affect was associated with a greater antibody response to vaccination.
(27) The same trait 
was associated with decreased vulnerability to upper respiratory infections. Dispositional optimism, as deﬁ  ned by generalized posi-

tive expectations for the future, is positively related to measures of cellular immunity in cancer and HIV patients only when stressors are brief, relatively straightforward and controllable whereas the reverse relationship is observed when stressors are complex, persis-tent, and uncontrollable.
(28)
Mechanisms of the relationship between stressful life events,

(28)
Mechanisms of the relationship between stressful life events, 
emotions, and immunity are rarely investigated because of the many biobehavioural pathways that can be implicated in mediating relationship. In view of the postulated immunosuppressive effects of glucocorticoids, it has been important to demonstrate that not all effects of stress on immunity are mediated by activation of the hypothalamic–pituitary–adrenal axis. As an example, implantation of a corticosterone pellet after adrenalectomy in rats that were sub-mitted to inescapable electric shocks so as to prevent the stress-induced increases in plasma corticosterone did not alter the decreased proliferative response of blood lymphocytes observed in stressed rats.
(29) Evidence for a role of the sympathetic nervous

(29) Evidence for a role of the sympathetic nervous 
system was provided by experiments using beta-adrenergic recep-tor antagonists or sectioning of the sympathetic nerve innervating the spleen. For instance, administration of propranolol prevented the decreased lymphoproliferative response in rats re-exposed to the cage in which they had been previously exposed to inescap-able electric shocks.
(30) Other possible biological mediators are 
CRH and endogenous opioids. In the clinic, the search for possible biological mediators of the relationship between stress and immu-nity is not easily found, and often confounded by the impact of stress and negative emotions on illness behaviour, via for instance deterioration in health-promoting behaviour and alterations in symptom perception.
(31)
Susan Lutgendorf at the University of Iowa recently summarized

(31)
Susan Lutgendorf at the University of Iowa recently summarized 
the current view of interactions between health behaviours and psychosocial and biological factors that can combine to affect a multitude of disease outcomes in a biopsychosocial model (Fig. 2.3.10.1).
(32)
The immune system as a true sensory organ
In a recent longitudinal study on the relationship between positive affect and clinical signs during a bout of inﬂ  uenza in volunteers 
inoculated with rhinovirus or influenza virus, production of inﬂ ammatory mediators by cells of the innate immune system in 
the nasal secretions was associated with reduced positive affect.
(33)
Since 1-day lagged analyses showed that daily production of inﬂ  am-
matory mediators predicted lower positive affect on the next day, it was difﬁ  cult to interpret these ﬁ  ndings in terms of the previously

matory mediators predicted lower positive affect on the next day, it was difﬁ  cult to interpret these ﬁ  ndings in terms of the previously 
described relationship between emotions and immunity, negative emotions, or decreased positive affect increasing innate immunity. On the contrary, the authors interpreted their ﬁ  ndings as support-
ing a causal association between pathogen-induced local cytokine production and changes in positive affect.2.3.10  psychoneuroimmunology

SECTION 2  the scientific basis of psychiatric aetiology 208
Fig. 2.3.10.1  The ﬁ  gure illustrates the biopsychosocial model in health psychology. The interaction between psychosocial processes (Box A), biological factors (Box B), 
and health behaviours (Box C) leads to a vulnerability (or resistance) to illness (Box G), disease onset and symptoms (Box H), progression, exacerbation, recovery, with 
concomitant quality of life (Box I), and survival with concomitant quality of life (Box J) via processes involving neuroendocri ne and immune mechanisms (Box F). Effects 
of life stress (Box D) are ﬁ  ltered through psychosocial processes (Box A) and health behaviours (Box C) in their resultant eff ects on downstream mechanisms. Health 
psychology interventions (Box E) can modulate effects of psychosocial processes and health behaviours on neuroendocrine and imm une mechanisms and on resultant

psychology interventions (Box E) can modulate effects of psychosocial processes and health behaviours on neuroendocrine and imm une mechanisms and on resultant 
health outcomes. There are also pathways between biobehavio ural factors and disease outcomes not involving neuroendocrine or im mune mechanisms, but other 
pathways are not included in this ﬁ  gure. Psychosocial processes (A) encompass psychological and social factors, particularly t hose that involve interpretation of and 
response to life stressors. These include personality variables (e.g., optimism, hostility, and negative affect), mental health  and mood variables (e.g., depression and anxiety), 
coping, social support, spirituality, and sense of meaning. Health behaviours (C) include drug and alcohol use, smoking, sleep,  nutrition, exercise, adherence to medical

coping, social support, spirituality, and sense of meaning. Health behaviours (C) include drug and alcohol use, smoking, sleep,  nutrition, exercise, adherence to medical 
regimens, physical examinations, risk screenings, and risky sexual behaviours, among others. Health psychology interventions (E ) can be used to alter psychosocial 
processes (A: e.g., decrease depression, increase coping) or improve health behaviours (C: e.g,. smoking cessation) to provide a more positive inﬂ  uence on neuroendocrine 
and immune factors and perhaps slow disease progression/exacerbation. Interventions include cognitive behavioural stress manage ment (CBSM), relaxation, hypnosis, 
meditation, emotional disclosure, adherence-based interventions, sleep hygiene, exercise, social support groups, psychotherapy,  imagery, distraction, behavioural pain

meditation, emotional disclosure, adherence-based interventions, sleep hygiene, exercise, social support groups, psychotherapy,  imagery, distraction, behavioural pain 
management, yoga, massage, biofeedback, drug/alcohol prevention/rehabilitation, psychotherapy, and behavioural conditioning. Th ese interventions can be used 
at all points of the trajectory of the disease or condition. Box F shows selected mechanisms involved in the bidirectional inte ractions between neuroendocrine and 
immune axes that mediate the relationships between biobehavioural factors (A–D) and disease outcomes (G–J). This by no means is  an all-inclusive list of mechanisms, 
but it represents some of the commonly studied factors in this literature. Once vulnerability (G) has been established, continu ed interaction with positive or negative

but it represents some of the commonly studied factors in this literature. Once vulnerability (G) has been established, continu ed interaction with positive or negative 
psychosocial factors (A: e.g., depression/social support), dise ase factors (B), adaptive/maladaptive health behaviours (C) and stress (D) will contribute to expression (or 
lack thereof) of disease symptoms (H), disease-free intervals/progression/exacerbation, and quality of life (e.g., functional, physical, emotional, and social well-being) (I), 
and survival (J). HPA, hypothalamic–pituitary–adrenocortical axis; SAM, sympathoadrenomedullary axis; HPG, hypophyseal pituitar y gonadal axis; OT, oxytocin; DA, 
dopamine; 5HT, seratonin; GH, growth hormone; NKCC, natural killer cell cytotoxicity; CTLs, cytotoxic lymphocytes; MÐ, macrophage; IL-1, interleukin 1; IL-6, interleukin

dopamine; 5HT, seratonin; GH, growth hormone; NKCC, natural killer cell cytotoxicity; CTLs, cytotoxic lymphocytes; MÐ, macrophage; IL-1, interleukin 1; IL-6, interleukin 
6; TGFÐ, transforming growth factor beta; Ab, antibody; and VEGF, vascular endothelial growth factor. (Reprinted from Brain Beh aviour and Immunity, 17(4), ASK 
Lutgendorf and Es Costanzo, Psychoneuroimmunology and health psychology: an integrative model, 225–32, Copyright 2003, with per mission from Elsevier.)

209
T o understand this interpretation, it is necessary to replace the 
relationship between the immune system and the brain in the context of regulatory immunophysiology. If the brain communi-cates with the immune system via neuroendocrine factors and autonomic neuronal pathways, it is probably because the immune system needs the brain to regulate its function and do what it can-not do by itself, (i.e., engage the whole organism in the ﬁ  ght against 
microbial pathogens). If this is the case, then it ensues that the immune system needs to inform the brain of its state of activity. In other words, brain-to-immune communication pathways need to be activated by immune-to-brain communication pathways. This interpretation makes the immune system a true sensory organ, specialized in the detection of the non-self and able to transmit this information to the brain.
Looking through the mirror: immune modulation of 
emotions and mood

The isolation, cloning, and expression of proinﬂ  ammatory cyto-
kines and their receptors in the late 1980s, coupled with the dis-covery of pathogen-associated molecular patterns (PAMPs) and their pathogen recognition receptors (PRRs), are two of the major advances in immunology that set the stage for deﬁ  ning immune-
to-brain communication pathways. Interleukin-1 (IL-1) is a pro-typical proinﬂ  ammatory cytokine that is released from activated 
macrophages following activation of some PRRs. Other proinﬂ  am-
matory cytokines include tumour necrosis factor (TNF- α), IL-6,

matory cytokines include tumour necrosis factor (TNF- α), IL-6, 
and IL-8. Injection of IL-1 or TNF-í, either systemically in the form of intraperitoneal administration or centrally via an intracerebro-ventricular route, induces the classical signs of illness, including fever, activation of the hypothalamic–pituitary–adrenal axis, and sickness behaviour, as evidenced by decreased interaction with the physical and social environment, reduced appetite, disappear-
ance of body care activities, fatigue, malaise, and mild cognitive impairments.
(34–37) These actions take place in the brain since pre-
treatment of rats with the speciﬁ  c antagonist of IL-1 receptors into 
the lateral ventricles of the brain signiﬁ  cantly impairs the ability of 
systemic IL-1 to cause behavioural deﬁ  cits.
At the molecular and cellular levels, it is now clear that IL-1 and 
other proinﬂ  ammatory cytokines produced by activated innate

other proinﬂ  ammatory cytokines produced by activated innate 
immune cells in the periphery during the inﬂ  ammatory response 
induce expression of the same cytokines in innate immune cells of the brain, including meningeal and perivascular macrophages, microglial cells in the brain parenchyma and mast cells. Peripheral cytokines are relayed to the brain via a humoral pathway involving 
the action of PAMPs on PRRs located in circumventricular organs 
at the interface of the brain and periphery and a neural pathway involving activation of the afferent nerves that innervate the body region in which the inﬂ  ammatory response takes place. At the 
organism level, this central representation of the peripheral inﬂ  am-

matory response imposes a new mode of functioning on the brain so as to allow the organism to better cope with infection. The elevated body temperature actively maintained by the increased thermogenesis and decreased thermolysis that characterizes the fever response promotes a number of immune events and reduces microbial proliferation. At the same time, zinc and iron that are normally essential for cellular multiplication are sequestered and acute phase proteins including complement proteins are synthe-sized by hepatocytes to help killing microbial pathogens. The increased glucocorticoid levels that occur as a consequence of the 
hypothalamic effect of cytokines negatively feed back on activated innate immune cells and signiﬁ  cantly limit the intensity and dura-
tion of the inﬂ  ammatory response. Sickness behaviour itself helps

tion of the inﬂ  ammatory response. Sickness behaviour itself helps 
to reduce physical activities detrimental to thermogenesis and facilitates the reduction of thermolysis. It also limits the spread of infection within the social group by reducing social activities and reduces pain that is enhanced by proinﬂ  ammatory cytokines.
Once an infection, and therefore cytokine synthesis, resolves over 
the time course of a few days, behavioural symptoms of sickness normally disappear. However, if the infection does not resolve, or if there is ongoing autoimmune inﬂ  ammatory processes of a chronic 
nature, such as rheumatoid arthritis, multiple sclerosis, inﬂ  amma-
tory bowel disease, the synthesis of cytokines and their downstream products continues to be elevated. The chronic action of proin-ﬂ ammatory cytokines acting in the brain has now led to the

tory bowel disease, the synthesis of cytokines and their downstream products continues to be elevated. The chronic action of proin-ﬂ ammatory cytokines acting in the brain has now led to the 
hypothesis that these very same proteins are somehow involved in development of affective disorders such as depression. In the clinic, this hypothesis is supported by the high prevalence of major depressive disorders that is observed in patients with a chronic inflammatory condition
(38) and the observation that chronic 
administration of recombinant IL-2 and/or IFN- α to cancer or 
hepatitis C patients induces alterations in mood that are character-istic of depression. In the laboratory, acute or chronic activation of the peripheral immune system induces depression-like behaviour that is apparent even when sickness behaviour has dissipated.
(39)
A leading candidate protein for this effect is a cytokine-activated enzyme known as indoleamine 2,3 dioxygenase (IDO)
(40) which

(39)
(40) which 
has an ubiquitous cellular localization and is also present in the brain. This enzyme degrades tryptophan, an essential amino acid that is required for the synthesis of the mood-regulating neu-rotransmitter serotonin. Increased degradation of tryptophan associated with inﬂ  ammation results in a relative deﬁ  cit in brain 
serotonin neurotransmission that can precipitate depression and an increased production of tryptophan neuroactive derivatives, including kynurenine, 3-hydroxy kynurenine, and quinolinic acid. These molecules act as agonists or antagonists of the NMDA receptor. Since brain IDO enzymatic activity is increased during activation of the peripheral immune system, these molecules gain access to the brain because they freely cross the blood–brain barrier. In addition, these metabolites are also produced in the 
brain.

brain.
There is accumulating evidence that activation of immune-to-
brain communication pathways is responsible not only for the adaptive sickness behavioural response and the maladaptive syndrome of depression that develops in vulnerable individuals but also for the symptom burden that is experienced by physically ill patients, including fatigue
(41) (see Fig. 2.3.10.2), pain(42), sleep 
disorders,(43) and impaired learning and memory.(44)
Concluding comments
A few years ago, scientists who proffered the idea that mood disor-ders could be induced by an infective process were considered heretic. That view has changed considerably with the discovery that cytokines from the immune system act as elements that permit active communication between the brain and the rest of the body. Indeed, it was in 1984 when a pioneering scientist in psychoneuro-immunology, J. Edwin Blalock, proposed that the immune system 2.3.10  psychoneuroimmunology

SECTION 2  the scientific basis of psychiatric aetiology 210
is really a sixth sensory system.(45) Humans cannot see, smell, 
touch, hear, or taste pathogenic micro-organisms. However, cells of the immune system, whether they be T cells, B cells, macrophages, microglial cells, or dendritic cells are uniquely endowed with the molecular machinery to detect an endless array of pathogens. One way that the immune system informs the brain that a pathogen has entered the body is by immune cells recognizing these invaders. These leukocytes respond by releasing proinﬂ  ammatory cytokines, 
which act as messenger systems to alert the brain that something is amiss in the periphery. The foundation for this conceptual system has strengthened during the last 20 years. It forms the intellectual basis for the notion that emotions are regulated by the immune system, and the immune system affects expression of emotions.

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211
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2.4
The contribution of genetics
Contents
 2.4.1 Quantitative genetics
 2.4.2 Molecular genetics
2.4.1 Quantitative genetics
Patterns of inheritance
Our understanding of how traits and disorders are passed from one

2.4.2 Molecular genetics
Our understanding of how traits and disorders are passed from one 
generation to the next began with the work carried out by an Augustinian monk, Gregor Mendel. Although Mendel’s published work in 1866 was initially ignored, its rediscovery at the beginning of the twentieth century heralded the beginning of modern genet-ics. Mendel’s experiments on pea plants and his observations of the patterns of inheritance of certain characteristics led to the develop-ment of his particulate theory of inheritance. It was only later in 1909 that the units of inheritance that he had described were named genes and alternative forms of a gene were termed alleles. It was also at this time that the terms phenotype, used to describe the observed characteristic, and genotype, used to refer to the genetic endowment, were introduced.
Mendel’s laws

Mendel examined clear-cut dichotomous characteristics such as smooth versus wrinkled coats in peas. He ﬁ  rst noted that when 
parents of different types were crossed, the ﬁ  rst generation (F1) 
offspring displayed uniformity  of that characteristic. He inferred 
that this uniformity was due to one phenotype being dominant and the other being recessive. Thus, when homozygous parents AA and aa produced heterozygote Aa offspring, these offspring dis-played the phenotype of the AA parent rather than manifesting a phenotype intermediate to those of both parents.Mendel then demonstrated that when the F1 heterozygotes (Aa) 
were intercrossed (Aa × Aa), segregation  resulted in the second F2 
generation showing recessive and dominant phenotypes in the ratio of 1 to 3. He then inferred that this F2 generation consisted of three types (AA, Aa, and aA, aa) occurring with a probability of 1:2:1.
Finally, Mendel showed that when the transmission of two

Finally, Mendel showed that when the transmission of two 
different phenotypic traits was studied, they showed independent 
assortment . We now know that independent assortment occurs 
when the genes coding for these traits are either located far apart on the same chromosome or are on different chromosomes (see linkage).
Single-gene disorders
Although disorders showing a simple Mendelian pattern of inheritance are rare, they tend to be clinically severe and collec-tively impose a signiﬁ  cant burden.
For autosomal dominant  disorders to manifest themselves, only

For autosomal dominant  disorders to manifest themselves, only 
one disease allele is necessary, i.e. both heterozygotes as well as homozygotes (those who carry both disease genes) will be affected. In most instances, where there is one affected parent who is a het-erozygote for the disease, approximately 50 per cent of the offspring will show the disorder. Autosomal disorders tend to be severe and manifest themselves in every generation. Huntington’s disease and acute intermittent porphyria are examples of autosomal dominant conditions that are often present with psychiatric symptoms.
Autosomal recessive  conditions such as phenylketonuria require 
the presence of two disease alleles to show clinical manifestations 
of the disorder. Thus, they often appear to skip generations. These

of the disorder. Thus, they often appear to skip generations. These 
disorders usually occur in the offspring of two ‘carrier’ heterozy-gote parents and are more common where there is a high rate of consanguinity (e.g. marriages between cousins) as these inbred populations will show greater homozygosity at all loci.
The other group of single-gene disorders consists of sex-linked
conditions such as fragile X syndrome. Normal females have two X chromosomes whereas normal males have one X chromo-some and one Y chromosome. Thus, for recessive disorders on the X chromosome, if the mother is a carrier (X*X) and assuming that the father is unaffected (XY), half of her sons will manifest the disorder (X*Y) and half of her daughters will be carriers (X*X). Where the father is affected by an X-linked recessive condition, all the daughters will be carriers. As sons have to inherit their

213
X chromosome from their mother, there will be an absence of 
father to son transmission. X-linked dominant conditions are 
extremely rare.
Continuous traits
Mendel’s laws are based on the transmission of dichotomous 
characteristics, yet many important human phenotypes such as 
height, weight, and blood pressure are continuously distributed. 
However, we are able to show that Mendelian principles can also be 
applied for these types of quantitative traits.
Let us ﬁ  rst consider a phenotype measured on a continuous scale 
which results from the inﬂ  uence of a single gene with two alleles 
A1 and A2 (see Fig. 2.4.1.1). We can now describe the phenotypes of 
the three possible genotypes in terms of a quantitative value on the 
continuous scale. A1A1 has a value of − a; A2A2 has a value of + a;
and A1A2, the heterozygote, has a value of d. When d = 0, A1A2 lies 
exactly half way between A1A1 and A2A2, that is the genetic contri-

bution is entirely additive. When d = − a, A2 is recessive to A1and
when d = +a, A2 is dominant to A1.
At the simplest level, we assume that there are no dominance 
effects and that there is no mutation, selection, migration, or 
inbreeding in the population. If p is the frequency of allele A1and
q is the frequency of A2 in the population where p + q = 1 then the 
frequency of genotypes can be expressed as follows:
A1A1A1A2A2A2
p2 2pq q2
This is known as the Hardy–Weinberg equilibrium. If we now 
simplify further and state allelic frequencies where p = q = 0.5, then 
the phenotypic values of A1A1, A1A2, and A2A2 would be distrib-
uted in the population with relative frequencies of 1:2:1.
Now if we consider a trait which results from two genes each of 
which has two alleles of equal frequency and additive effect, there

which has two alleles of equal frequency and additive effect, there 
would be ﬁ  ve possible phenotypic values with relative frequencies 
of 1:4:6:4:1. Overall as the number of genetic loci ( n) increases, the 
number of phenotypic values increases (2 n + 1) and the distribu-
tion of phenotypic values more closely approximates a normal 
distribution. It is thought that most quantitative or continuous 
traits result from the additive action of genes at many loci which 
is otherwise known as polygenic  inheritance. Where familial 
transmission is explained by environmental factors as well as 
by multiple genes, we then call this a multifactorial  mode of 
inheritance.
Complex disorders and irregular phenotypes
(a) Polygenic/multifactorial threshold models
Most common human psychiatric and medical disorders such as

Most common human psychiatric and medical disorders such as 
schizophrenia, diabetes, and heart disease do not show a Mendelian 
pattern of inheritance. Neither can they be considered as continu ous 
traits in that people are described as being affected or unaffected. However, these conditions could be regarded as quasi-continuous 
in that those who are affected can be graded along a continuum of 
severity. It is possible to extend this to assume that there is an 
underlying liability to develop the disorder which is continuously 
distributed in the population. Those who pass a certain threshold 
manifest the condition. If the underlying liability to develop the 
disorder is inherited in a polygenic or multifactorial fashion, 
then we can assume that the distribution will be approximately 
normally distributed (Fig. 2.4.1.2). The genetic liability of relatives

normally distributed (Fig. 2.4.1.2). The genetic liability of relatives 
of affected individuals will be increased and their liability distribu-
tion will be shifted to the right (Fig. 2.4.1.2). Thus, the proportion 
of relatives above the disease threshold will be greater compared 
with the general population. If we know the proportion of affected 
relatives of probands and the proportion of those affected in the 
general population, it is possible to calculate the correlation in 
liability between pairs of relatives using this type of model.
(b)  Single major locus model and atypical patterns of 
Mendelian inheritance
An alternative to a polygenic model of complex disease is a single 
major locus model. Single-gene disorders do not always show typi-
cal Mendelian patterns of inheritance. For example familial trans-
mission can be modiﬁ  ed by variable expression  and penetrance .

Some conditions can show great variability in terms of clinical 
expression. For example neuroﬁ  bromatosis, an autosomal domi-
nant disorder can express itself as the full blown disorder or merely 
as a few café-au-lait spots. Penetrance is deﬁ  ned as the probability 
of manifesting the disorder given a particular genotype. For 
Mendelian disorders this is always 1 or 0, but irregular patterns of 
inheritance may occur because of incomplete penetrance where 
the probability of manifesting the disorder is greater than 0 but less 
than 1.
Finally, there are now molecular explanations for other types of 
unusual patterns of inheritance for single genes. Anticipation where 
disorders show a progressively earlier onset and greater severity

disorders show a progressively earlier onset and greater severity 
with subsequent generations is now known to be explained by her-
itable unstable nucleotide repeat sequences (see later). Huntington’s 
chorea and fragile X syndrome are examples of disorders caused 
by heritable unstable repeats. For some conditions such as the 
Angelman syndrome and the Prader–Willi syndrome, manifesta-
tion of the disorder depends on the parental origin of the gene. 
This is known as imprinting.
Fig. 2.4.1.2 A polygenic or multifactorial threshold model of disease 
transmission.
Fig. 2.4.1.1 A phenotype, measured on a continuous scale, resulting from a 
single gene with two alleles A1 and A2.
2.4.1 quantitative genetics

SECTION 2  the scientific basis of psychiatric aetiology 214
(c) Other models
Alternative explanations of how complex conditions such as 
psychiatric disorders are inherited include mixed and oligogenic patterns of transmission. A mixed model includes a major gene and a polygenic/multifactorial contribution. However, for many of these disorders, genes of major effect may not exist. It may be that these irregular phenotypes are best explained by oligogenic models where the co-action or interaction of a small number of genes contributes to the disorder. These issues remain to be resolved by molecular genetic studies (see later).
Components of phenotypic variation
We will now consider the different inﬂ  uences that contribute to 
phenotypic variation in a population. The total variation in an observed trait (phenotype v
p) at the simplest level (ignoring non-
additive effects) can be partitioned into a proportion due to genetic inﬂ uences ( v

g), a component explained by shared environmental 
factors ( vc), and a remainder accounted by non-shared environ-
mental factors which includes error ( ve):
vp=vg+vc+ve
Shared or common environmental inﬂ  uences are aspects of the 
environment that result in greater similarity of family members for a given phenotype. Non-shared environmental factors refer to environmental inﬂ  uences that have effects which are speciﬁ  c to 
individuals and that contribute to phenotypic differences between family members.
Although we have so far only considered one type of genetic con-
tribution, the genetic variance v
g can be further subdivided into 
variance due to additive genetic inﬂ  uences ( va) and dominance 
effects ( vd).
The relative inﬂ  uence of genetic factors is expressed as heritability
and when deﬁ  ned as the proportion of the total phenotypic variance

and when deﬁ  ned as the proportion of the total phenotypic variance 
attributable to additive genetic variance, is known as narrow-sense 
heritability :
hn2 = va/vp.
Heritability is also sometimes used to describe the proportion of 
variance explained by the total  genetic variance (additive and non-
additive genetic variance) and it is then known as broad-sense 
hb2 = va/vg.
Similarly we can estimate the proportion of the total phenotypic 
variance explained by shared environment where c2 = vc/vp and the 
remaining proportion attributable to non-shared environmental factors and error ( e
2).
It is important to remember that the estimate of heritability and

2).
It is important to remember that the estimate of heritability and 
the contribution of shared environment and non-shared environ-ment are proportions of total variation within a given population, i.e. these parameters tell us about sources of difference between individuals in a population and have no meaning at an individual level. For example, if an individual was selected from a population where IQ had been shown to have a heritability of 50 per cent, it could not be said that 50 per cent of that individual’s IQ was deter-mined by genes. Another important point is that these estimates are speciﬁ  c to the population studied and may differ for other 
populations. Finally, the contribution of genetic and environmen-tal inﬂ  uences to a phenotype does not allow any inferences about 
the extent to which that phenotype is modiﬁ  able by environmental

the extent to which that phenotype is modiﬁ  able by environmental 
factors. For example, phenylketonuria is a Mendelian condition that is determined by the presence of a single-gene mutation. Y et the clinical manifestations of the syndrome are prevented by dietary intervention.
Non-additive genetic effects
So far we have simplistically assumed that phenotypic variation is inﬂ uenced in an additive fashion. However, the contribution of 
genes and environment is more complex than this. We have already referred to genetic dominance  effects where there is non-additive 
interaction of alleles within a locus. Another potential source of inﬂ uence is the non-additive interaction between alleles at differ-
ent loci which is known as gene–gene interaction or epistasis .
Gene–environment interaction
Gene–environment interplay represents another important form of 
non-additive genetic contribution to complex phenotypes.(1) The

non-additive genetic contribution to complex phenotypes.(1) The 
term gene–environment interaction (G × E) is used here to refer to 
individual genetic differences in response to speciﬁ  c environmental 
factors. In the presence of gene–environment interaction, individu-
als who are at genetic risk of a disorder do not manifest the condi-
tion unless they are exposed to a speciﬁ  c environmental risk factor. 
Gene–environment interaction also means that not all those exposed 
to an environmental risk factor will show disorder. Later, we con-
sider direct investigation of gene–environment interaction through 
molecular genetic studies. Twin and adoption study designs have also been used to examine G × E, in an indirect way. Here, genetic 
liability is inferred by virtue of having affected relatives rather than through possession of a speciﬁ  c genetic risk variant.
Gene–environment correlation

Gene–environment correlation further adds to the complexity of

Gene–environment correlation further adds to the complexity of 
interplay between genes and environment. Gene–environment correlation arises when a person’s genotype is correlated with the environment that they are exposed to. For example, sociable par-ents not only endow their children with genes but also provide an environment that encourages greater sociability in their children (passive gene–environment correlation). Moreover, positive gene–environment correlation would result where a sociable child actively seeks out more situations where socializing occurs (active gene–environment correlation) or where he or she evokes friendly responses in others (evocative gene–environment correlation). There is evidence that many important environmental risk factors in psychiatry (for example, life events) do correlate with genetic risk for speciﬁ  c disorders (for example, depression). Where that is

the case, genetically sensitive designs are needed to investigate whether environmental risk factors have true environmentally mediated risk effects on disorder or whether the association has arisen because of genetic factors contributing to both the environ-mental risk exposure and disorder.
The presence of gene–environment interaction and gene–environ-
ment correlation highlights that the action of genes and environ-ment must be considered together. Another important point is that in traditional twin study designs, G × E and G − E correlation effects 
are subsumed within the heritability estimate or in some circum-stances the environmental variance component (see twin studies).

215
Research methods
Family, twin, and adoption studies
So far we have considered the theoretical basis of inheritance and 
possible sources of phenotypic variation and familial resemblance. Clearly, the investigation of the genetic basis of psychiatric disorders ﬁ  rst requires us to examine to what extent genes and 
environment contribute to a given disorder or trait. Secondly, we need to know how genes and environmental inﬂ  uences exert their 
risk effects and ﬁ  nally we have to investigate the genetic basis of 
disorders at a molecular level.
Traditional methods in psychiatric genetics research include family, 
twin, and adoption studies. Family studies enable us to examine to what extent a disorder or trait aggregates in families. Familiality of a disorder can of course by explained by shared environmental inﬂ  u-
ences as well as by shared genes. Twin and adoption studies allow us to disentangle the effects of genes and shared environment.
Family studies
(a) Methods

Family studies allow us to determine whether a disorder aggregates in families by examining the rate of disorder in the relatives of affected individuals (probands) and comparing this with the rate of disorder in the general population or in a control group. Alternatively we can compare the frequency of disorder in the relatives of probands with the frequency among relatives of a control group of normal individuals or those with another disorder.
There are two types of family studies. The family history  method 
is more economical in that the psychiatric history is taken from the proband. However, given that most individuals are unlikely to know as much about family members as about themselves, this method results in an underestimate of diagnoses in relatives. A more thorough but more time-consuming approach is the family study

method where all available relatives are directly interviewed.
(b) Ascertainment
An important issue is how a family study sample is ascertained. Ideally, probands should be ascertained independently from each 
other. This is unlikely to pose a problem for rare disorders. However, for more common conditions where a series of cases is collected, for example, by consecutive referrals of the disorder to a particular hospital, it is possible that families include d in a family study contain
more than one proband. This is known as multiple incomplete ascertainment. Complete ascertainment, where all affected indi-
viduals in a given population are included, is rarely possible and in 
most instances probands are identiﬁ  ed after some selection process 
(e.g. referrals to a particular hospital). Thus, factors inﬂ  uencing 
selection, such as comorbidity and help seeking may also inﬂ  uence 
observed patterns of familial aggregation.
(c) Age correction

For genetic studies, we are interested in the proportion of individuals who have ever had the disorder (lifetime prevalence) rather than the proportion who show the disorder at one point in time (point prevalence). However, a difﬁ  culty encountered when carrying out 
family studies is that the observed rates of disorder will also depend on the age of the individual, the risk period for the disorder, and whether or not the individual has lived through that risk period. Thus, some members may not yet have reached the age of risk for the disorder, some are currently unaffected but will become 
affected at some later point, and others may have died whilst still unaffected. The most appropriate method is to correct for age and express the rate of disorder in relatives as the morbid risk (MR)  or 
lifetime expectancy.

There are many methods of age correction, of which the Slater-
Stromgen adaption of Weinberg’s shorter method is the most straightforward. The MR of the disorder can be estimated as the number of affecteds (A) divided by the bezugsziffer  (BZ) where the 
BZ is calculated as:
Â
i[a1]wi+A
and where wi is the weight given to the ith unaffected individual 
based on their current age. The most accurate approach is to use an empirical age of onset distribution from a large separate sample, for example a national registry of psychiatric disorders, to obtain the cumulative frequency of disorder over a range of age bands, from which weights can be derived.
Another approach is to carry out life table analysis. The distribu-

tion of survival times (or times to becoming ill) is divided into a number of intervals. For each of these one can calculate the num-ber and proportion of subjects who entered the interval unaffected and the number and proportion of cases that became affected dur-ing that interval as well as the number of cases that were lost to follow-up (because they had died or had otherwise ‘disappeared from view’). Based on these, the numbers and proportions ‘failing’ 
or becoming ill over a certain time interval (usually taken as the

or becoming ill over a certain time interval (usually taken as the 
entire period of risk) can be calculated. A further alternative is to use a Kaplan Meier product limit estimator. This allows one to esti-mate the survival function directly from continuous survival or failure times instead of classifying observed survival times into a life table. Effectively this means creating a life table in which each time interval contains exactly one case. It therefore has an advan-tage over a life table method in that the results do not depend on grouping of the data.
Twin studies

Identical or monozygotic twins, by virtue of arising from the fertil-ization of one egg, share 100 per cent of their genes. Non-identical or dizygotic twins are from two fertilized eggs and like full biologi-cal siblings share on average 50 per cent of their genes. Thus, assuming that monozygotic twins and dizygotic twins share envi-ronment to the same extent, monozygotic twins would share great-er similarity than dizygotic twins for a disorder that is genetically inﬂ uenced. Twin studies are an important method for disentan-
gling the effects of genes and shared environment and can be used to estimate the contribution of genetic inﬂ  uences, shared environ-
mental factors and non-shared environmental factors to the total variation for a given trait or disorder.
For continuous traits, twin similarity is expressed as an intraclass 
correlation coefﬁ  cient where:
r
mz = h2+c2
rdz = 0.5 h2+c2
Thus, from observed monozygotic and dizygotic correlations for a

r
mz = h2+c2
Thus, from observed monozygotic and dizygotic correlations for a 
given trait we can calculate heritability from the above equations where h
2 = 2( rmz − rdz), c2 = 2 rdz − rmz, and e2 is the remaining 
variance = 1 − h2 − c2 (see path analysis below).2.4.1 quantitative genetics

SECTION 2  the scientific basis of psychiatric aetiology 216
For dichotomous characteristics (e.g. affected with a disorder 
and unaffected), twin similarity is expressed as concordance rates. Apairwise concordance rate  is estimated as the number of twin 
pairs who both have the disorder divided by the total number of pairs. However, where there has been systematic ascertainment, for example a twin register, it is preferable to report a probandwise 
concordance rate  which is calculated as the number of affected 
twins divided by the total number of cotwins.
(a) Ascertainment
One potential source of bias in twin studies stems from ascertain-ment procedures. For example, affected twins referred to a speciﬁ  c

One potential source of bias in twin studies stems from ascertain-ment procedures. For example, affected twins referred to a speciﬁ  c 
study or volunteer samples are likely to include more twin pairs who are monozygotic and who are concordant. Ascertainment of twin pairs through hospital registers overcomes this problem to some extent, but for some disorders may be biased by the process of referral. Population-based samples overcome these biases, although when examining disorders rather than traits extremely large sample sizes are required to obtain an adequate number of affected individuals.
(b) Zygosity

A further potential source of error is in the assignment of zygosity. Ideally zygosity should be determined by DNA typing. However, it may be more practical to use a twin similarity questionnaire which includes questions such as whether the twins share the same hair/eye colour, and whether they look alike as two peas in a pod. This method of assigning zygosity is simple and inexpensive with a reported accuracy of over 90 per cent.
(c) Equal environments assumption
It is sometimes argued that a major drawback to the twin study method is that monozygotic twins may experience a more similar environment and may be treated more similarly than dizygotic twins. However, where there is evidence that monozygotic twins share greater environmental similarity than dizygotic twins it is difﬁ cult to infer whether this contributes to their similarity for

the disorder or whether this is the consequence of greater genetic similarity. There have been several approaches adopted to further explore this issue.
In some studies questionnaire measures of environmental shar ing 
(e.g. being dressed alike as children, sharing friends) have been used. These suggest that environmental sharing is indeed greater for monozygotic twins than for dizygotic twins. However, it appears that for many traits and disorders such as cognitive ability, person-
ality, depressive symptoms, and depressive disorder this degree of 
similarity for childhood environment does not account for mono-zygotic twin similarity for the trait. One way of disentangling cause and effect is to use direct observational studies. Although this method has not been much used, one study of young twins sug-gested that the greater similarity of parental responses to monozy-gotic twins compared to dizygotic twins appeared to be elicited by the twins themselves.

An alternative method of examining the effects of environmental 
sharing is to study twins who are mistaken about their zygosity. However, most studies which have used this method suggest that perceived zygosity is a less important inﬂ  uence on twin similarity 
than true zygosity.
Finally, the most powerful means of examining the effects of 
environmental sharing is to look at monozygotic twins who have been reared apart. However, such twin pairs are rare and have 
mostly been ascertained in a biased fashion. Nevertheless, studies of reared-apart twins have informed us that there is a substantial genetic contribution to cognition, personality, and psychosis.
(d) Comparability of twins
The ﬁ  nal potential criticism of the twin method is whether twins

The ﬁ  nal potential criticism of the twin method is whether twins 
can be regarded as representative of the general population given some important differences. Twin births are relatively common (1 in 80 births), although the number of dizygotic twins varies in different countries and is inﬂ  uenced by factors such as maternal 
age and multiparity, a family history of twins and increasingly, the use of fertility drugs. Twins are more likely to experience greater intrauterine and perinatal adversity and the experience of being brought up as a twin is unusual in itself. There is also some evi-dence that depression is more common in mothers of young twins than among mothers of singletons. However, these differences are only important if they result in different rates of disorder or symp-toms in twins compared to singletons. So far there is little evidence to suggest that the rate of psychiatric disorder in twins is any higher 
than amongst singletons.

Adoption studies
Adoption studies provide another means of teasing apart the effects 
of genes and environment. The basic method of the adoption study lies in comparing the rates of disorder in biological relatives and adoptive relatives. There are three main types of adoption study.
1The adoptee study : Here the rate of disorder in the adopted-
away offspring of affected individuals is compared with the rate of disorder in control adoptees whose biological parents are unaffected.
2The adoptee’s family study : In this design, the rate of disorder in 
the biological relatives of affected adoptees is compared with that among the adopted relatives.
3The cross-fostering study : This allows us to examine gene-
environment interaction by comparing the rate of disorder in adoptees who have unaffected biological parents and affected adoptive parents with the rate of disorder in adoptees who have affected biological parents and unaffected adoptive parents.

Although adoption studies allow us to examine the effects of 
both genes and environment, there are several potential drawbacks to the method. First, adoption is in itself an unusual event and there is a tendency for higher rates of some psychiatric difﬁ  culties 
such as antisocial personality traits amongst adoptees. Second, adoptive placements are not random in that adoption agencies are likely to attempt to match adoptive and biological parents for physical, social, and other characteristics. Nevertheless, despite these difﬁ  culties, adoption evidence has given much support to the 
role of both genes and environment for traits and behaviours such as cognitive ability and criminality.
Methods of analysis
Although the statistical methods used in quantitative genetics may

Although the statistical methods used in quantitative genetics may 
seem complex, the principles are straightforward. We will now consider the methods of analyses that are most commonly used for examining the contribution of genetic and environmental factors, to psychiatric disorders and traits.

217
Path analysis
Path analysis provides a simple diagrammatic method of estimating 
the contribution of genetic and environmental factors. The basic path diagram in Fig. 2.4.1.3 shows the sources of resemblance for phenotypes (P
1 and P2) in a pair of siblings. Using the rules of path 
analysis, the correlation between the siblings ( rsib) is derived by 
multiplying the path coefﬁ  cients for each connecting path and then 
summing these coefﬁ  cients. Thus
rsib = h× rg× h + c× c.
The genetic correlation rg is 1 for monozygotic twins who share 
100 per cent of their genes in common and is 0.5 for full siblings or dizygotic twins. Thus, using path analysis we obtain the equations described earlier where
r
mz = h2+c2
rdz = 1/2h2+c2
Model ﬁ  tting
Although we can simply estimate h2,c2, and e2 from the equations 
above for more complex data, solving multiple linear equations becomes difﬁ  cult. We may also wish to test alternative models, for

above for more complex data, solving multiple linear equations becomes difﬁ  cult. We may also wish to test alternative models, for 
example one where there is no genetic contribution or one where shared environmental inﬂ  uences are dropped. Model ﬁ  tting allows 
us to ﬁ  rst statistically test how well a given model explains the 
observed data and to then compare different models.
Computer packages such as Mx
(2) are all based on the same prin-
ciples. The raw data are read into the program and the researcher supplies the initial starting values for the unknown parameters (h,c, and e for a full genetic model). The program then iterates 
with different parameter estimates until values are found which give an optimum ﬁ  t (usually this involves maximizing a likelihood 
function or minimizing a χ
2). The goodness of ﬁ  t of the model is 
then assessed by examining the χ2 goodness of ﬁ  t where a smaller

then assessed by examining the χ2 goodness of ﬁ  t where a smaller 
value indicates a better ﬁ  t.
The ﬁ  t of a reduced model ( R) can then be compared against the 
full model ( F) by subtracting the χ2 values ( R − F). Alternatively 
the ﬁ  t of models can be compared by using the likelihood ratio test 
where twice the difference between the log likelihoods for each model (this approximates a χ
2 distribution) is calculated.
(a) Application of model ﬁ  tting
So far we have considered the inﬂ  uence of genes and environment 
on variation in a single phenotype using a traditional twin design. This type of analysis is known as univariate genetic analysis. 
However the most interesting questions in psychiatry are best addressed by more testing more complex models (See Kendler and Prescott
(3) for excellent examples). Designs that involve measuring 
the same phenotype over time and several phenotypes at the same

the same phenotype over time and several phenotypes at the same 
time (e.g. depression and anxiety) have been used to investigate comorbidity, the aetiological contribution to developmentalchanges over time and diagnostic boundaries. Studies that have employed such methods have yielded interesting ﬁ  ndings. For 
example, there is evidence that the same set of genes, but different non-shared environmental factors inﬂ  uence anxiety and depressive 
disorders (and symptoms). The contribution of genetic factors to depressive symptoms and IQ has been found to increase in adoles-cence compared to childhood. Family and twin studies of autism suggest that there is familial and genetic loading for a broader cog-nitive and social phenotype in relatives of those with narrowly deﬁ ned autism.
There have also been imaginative extensions of the twin design

There have also been imaginative extensions of the twin design 
that have allowed investigation of different questions. Each type of design has its own set of strengths and weaknesses. Thus having a variety of available methods is invaluable. Examples of different but related designs include studies of the children of twins,
(4) studies 
combining twins, siblings, half siblings, step siblings, and families of twins.
(5)
(b) Multiple regression analysis
Another commonly used method of analysing twin data is multiple regression analyses.
(6) Here the score of the co-twin C is predicted 
by the score of the proband twin P, the coefﬁ  cient of the relation-
ship or zygosity R and an interaction term PR. The partial regres-
sion coefﬁ  cients provide direct estimates of heritability and shared

sion coefﬁ  cients provide direct estimates of heritability and shared 
environment. The advantage of this method is that it can then also be used to test whether the magnitude of genetic contribution of extreme scores for a continuous trait differs from scores within the normal range. For example, such analyses suggest that the contribution of genetic factors to variation in very low IQ scores is low, unlike the contribution to IQ variation across the ‘normal range’ .
Twin and adoption study methods for 
investigating gene–environment interplay
Traditional twin study designs and analysis of MZ twin similarity

Traditional twin study designs and analysis of MZ twin similarity 
and difference that include both measured aspects of the environ-ment (e.g. reported life events) and phenotype (e.g. depression) can be used to test the extent to which the association of environ-mental factors with psychopathology is mediated by genetic and environmental pathways (gene–environment correlation). For example, one twin study showed environmentally mediated risk effects of childhood maltreatment on antisocial behaviour but different findings for corporal punishment where there were genetically mediated effects.
(7) Twin studies have also been used 
to demonstrate the importance of G × E. Kendler and colleagues 
(1995)(8) showed that those at higher genetic risk of a major depres-

sive disorder (inferred by lifetime ever diagnosis of major depression in MZ and DZ co-twins) were more sensitive to the depressogenic effects of adverse life events.
Adoption study designs provide a useful method for testing 
gene–environment interaction as post-natal environmental risk Fig. 2.4.1.3 A single path model of the sources of resemblance between twins 
or pairs of siblings. G1 and G2 are genotypes with correlation B, CE is common 
environment, P1 and P2 are phenotypes, and h and c are path coefﬁ  cients.

SECTION 2  the scientific basis of psychiatric aetiology 218
factors (apart from the very earliest) are experimentally separated 
from genetic risk. Such studies have shown evidence that the risk of antisocial behaviour is much higher in those who are not only at higher genetic risk (by virtue of having a parent with antisocial behaviour) but who are also exposed to adverse rearing environ-ments in the adoptive home.
Gene mapping
A more direct approach to locating and identifying genes involved in psychiatric disorders is to attempt to map them. Gene mapping technology has advanced at an astonishing pace over the past 20 years. Early studies in psychiatric disorders such as schizophre-nia
(9) had to rely purely on ‘classical’ genetic markers such as HLA

(9) had to rely purely on ‘classical’ genetic markers such as HLA 
antigens blood groups and various protein polymorphisms. Capabilities in systematic gene mapping, which involves mount-ing a search throughout the whole genome (i.e. the 22 pairs of autosomes and the sex chromosomes), only became possible after the discovery of markers based on variation in DNA length. The ﬁ rst of these were the restriction fragment length polymorphisms 
and these have largely been supplanted by single nucleotide poly-morphisms (SNPs). Informative combinations of markers are known as haplotypes. The Human Genome Project has led to a detailed map of common variation in the human genome. This public database of more than one million SNPs
(10) provides infor-

mation about the patterns of linkage disequilibrium between these markers that can guide selection of ‘tagging SNPs’ for gene map-ping studies. Such marker maps allow the genes contributing to traits or diseases to be located. The methods for mapping are linkage and association. Gene mapping is discussed further in Section 2.4.2.
Gene regulation
The human genome is much more complex than previously thought.
(11) Gene activity and expression (the process by which 
proteins are made) is regulated by inherited DNA and RNA, non-inherited mechanisms (epigenetics), endogenous biological factors such as hormones and environmental factors operating externally to the individual organism (e.g. toxins, psychosocial stress).
For example, non-coding sequences of DNA were previously

For example, non-coding sequences of DNA were previously 
thought to be ‘junk DNA ’ . There is increasing evidence that this is not the case and that such regions may play an important role in regulating gene activity. Gene activity is also altered by environ-mental factors.
(11) Animal studies have now shown that environ-
mental factors can alter the genome through measurable biological mechanisms, that these changes can be passed onto the next gen-eration and be subject to modiﬁ  cation. For example, maternal care 
giving behaviour early in life, notably high levels of licking and grooming of rat pups, has an effect on brain glucocorticoid recep-tor expression and sensitivity to stress in the offspring.
(12) This 
effect is observable even when non-genetically related pups are fostered to mothers who have low levels of licking. This ‘program-ming effect’ appears to be mediated by structural modiﬁ  cations of

effect is observable even when non-genetically related pups are fostered to mothers who have low levels of licking. This ‘program-ming effect’ appears to be mediated by structural modiﬁ  cations of 
DNA. The molecular mechanisms explaining this ‘epigenetic marking’ are beginning to be identiﬁ  ed and include DNA methyla-
tion and histone acetylation. These non-inherited effectspersist over two generations and in animals appear to be possibly reversible.Linkage
In linkage studies, rather than just studying the segregation of a disease in families, the co-segregation of the disease and a set of genetic markers is investigated. The aims are, ﬁ  rst, to detect linkage, 
indicated by the disorder and the marker co-occurring more often than would be expected by chance (i.e. not showing Mendelian independent assortment) and, second, to estimate the distance between a linked marker and the gene conferring to susceptibility to the disorder.

It is possible to detect linkage only in families containing at least 
one parent who is a double heterozygote (i.e. heterozygous at both the marker and the disease loci). T echnically such families are referred to as double back-cross or intercross/intercross matings but, for simplicity, we will just focus on the double back-cross type (Table 2.4.1.1). The table shows a double heterozygote parent where the alleles A and B are on one chromosome with a and b on the 
other. Consequently offspring of the types aaBb  or Aabb  result 
from recombination or crossing over between the homologous pair of chromosomes during meiosis. These types of offspring are called recombinants . Offspring of the same type as the parents (i.e. AaBb 
aabb ) are non-recombinant. We can then simply deﬁ  ne the recom-
bination fraction, θ, as the number of recombinants divided by 
total number of offspring.
For two loci that are very widely separated on the same chromo-

some (and all pairs of loci carried on to two different chromo-somes) independent assortment occurs and θ = 1/2. When the two 
loci are close together dependent assortment may be observed indi-cated by a recombination fraction of less than a half. The size of the recombination fraction depends on the physical distance between the two loci and (within certain limits) is proportional to it, so that for loci that are very close together recombination rarely occurs andθ tends to zero. Genetic distances estimated by linkage studies

are measured in centimorgans (cM) with 1 cM the equivalent of a recombination fraction of 0.01. For reasons that are not fully understood, recombination occurs more frequently in female than in male meioses. Hence, the size of the female human genome expressed in centimorgans is larger than the male genome. The sex-averaged size of the human genome is about 3700 cM. With reasonable sample sizes major gene effects can be conﬁ  dently 
detected over distances of around 10 to 15 cM. Hence, a whole genome search can be carried out using 200 to 300 polymorphic markers, provided they are approximately evenly spaced. A poly-
morphism  can be deﬁ  ned as a gene or sequence of DNA that occurs 
in two or more common forms. Classically, ‘common’ means 
an allele frequency of at least 1 per cent. SNP markers are common 
Table  2.4.1.1  Double back-cross mating
Parent 1 x Parent 2
 AB/ab ab/ab
Offspring AB/ab
Non-
recombinantAb/ab
RecombinantaB/ab
Recombinant ab/ab
Non-
recombinant

Non-
Non-
No linkage 1/4 1/4 1/4 1/4Linkage (1–θ)/2 θ/2 θ/2 (1– θ)/2

219
and biallelic. Sometimes combinations of allelic variants across dif-
ferent markers (haplotypes) are analysed in gene mapping studies.
Linkage analysis
The standard method of carrying out linkage analysis in humans is the lod score approach devised by Morton.
(9,13) Essentially, for a 
given set of data, lod scores are calculated over a range of values of θ between 0 and 0.5. Where the lod score reaches a maximum, 
provides the best (or maximum likelihood) estimate of θ. The lod 
score is so called because it is the common log of the odds that θ
has a certain value θ′; rather than a value of 0.5, i.e.
lod = log
10probability ( θ = θ′) .
probability ( θ = 0.5) 
By convention, a lod of 3 or more is accepted indicating that 
linkage has been detected, while a lod of −2 or less indicates that linkage can be excluded at that particular value of θ. A lod of 3 cor-
responds to odds on linkage of 1000:1 and to a nominal P value

responds to odds on linkage of 1000:1 and to a nominal P value 
of 0.0001. This therefore seems at ﬁ  rst sight to be a very stringent 
criterion. However, linkage between two loci taken at random is inherently unlikely
(13) and Morton’s(9) original argument took into 
account the low prior probability of linkage to arrive at a criterion that gave a posterior probability, or reliability, of 95 per cent. More recently researchers have been concerned about the effects of carry ing 
out many statistical tests in a genome-wide search for linkage and have sought to set an approp riate level of lod score to compensate for this. In fact, as it turns out, the original suggestion of a lod of about 3 is close to recent calculations of what lod is required to conclude in favour of genome-wide signiﬁ  cance.
(13)
As originally devised, the lod method deals purely with regular

(13)
As originally devised, the lod method deals purely with regular 
Mendelian traits. However, it can be readily adapted for detection of single genes that have incomplete penetrance by applying the general single major locus model discussed earlier. The main draw-back is that the model (as speciﬁ  ed by the penetrance values, and 
less critically the gene frequency) must be known accurately. Where the model is mis-speciﬁ  ed there is a high risk that linkage will fail 
to be detected.
A further difﬁ  culty is that diseases may show locus heterogeneity, 
i.e. there may be two or more different (and unlinked) loci where mutations result in similar phenotypes. There are many instances of this among rare Mendelian diseases. A good example is Usher’s syndrome causing deafness and retinitis pigmentosa, which can result from mutations in any one of six different genes. Subforms 
of common diseases can also show locus heterogeneity, the most

of common diseases can also show locus heterogeneity, the most 
relevant to psychiatry being early onset familial Alzheimer’s disease where autosomal dominant forms can result from mutations in three different genes, called presenilin 1, presenilin 2, and amyloid precursor protein. Although methods exist for detecting linkage in the presence of heterogeneity these have not so far in practice been of great help in psychiatric or other common disorders. Rather, the most frequent general strategy has been to focus on multiplex families (i.e. those containing multiple members with the disorder under study) and to make the following simplifying assumptions.
1 There are major gene subforms of the disorder in at least some 
families.
2 Although the mode of transmission is unknown, a reasonable 
guess at the deﬁ  ning parameters can be made.3 Although there may be locus heterogeneity in the disorder as a 
whole, within any given family there is likely to be homogeneity.

This has worked very well for several disorders, including, as we 
have just mentioned, Alzheimer’s disease, but it initially produced a rather confusing set of results from studies of schizophrenia and bipolar disorder. The most likely cause of this is that assumption 1 is incorrect and that subforms of these conditions resulting from major genes are very rare or perhaps non-existent. Consequently most recent studies use other linkage methods that do not rely on any assumptions about the mode of transmission. These concen-trate on affected siblings or other pairs of relatives both affected by the disorder.
Methods based on relative pairs

The underlying principle of the affected sib-pair approach is simple. For any given locus the probabilities that siblings share 0, 1, or 2 alleles that are identical by descent from their parents is respec-tively ¼, ½, ¼. On the other hand, if both members of a sib pair are affected by the same disease and we are studying a locus close to a gene that confers susceptibility to that disease, there will be increased allele sharing. This will occur irrespective of the mode of transmission of the susceptibility gene and hence simple non-parametric statistics can be used to test whether there is any per-turbation of the expected identical-by-descent proportions. Affected sib-pair methods are therefore robust and are now gener-ally considered to be the method of choice in detecting linkage in oligogenic or polygenic disorders. In order to be certain that a pair of siblings share alleles identical by descent, one needs to know their parents’ genotypes. Otherwise it could be that a shared

oligogenic or polygenic disorders. In order to be certain that a pair of siblings share alleles identical by descent, one needs to know their parents’ genotypes. Otherwise it could be that a shared allele identical by state results from one of the pair having inherited it from the father and the other from the mother. However, an advan-tage of using highly polymorphic single sequence repeat polymor-phisms is that it may not always be necessary to genotype parents, i.e. where the population is reasonably homogenous and where gene frequencies can be estimated, it is possible to compute the likelihood that a pair who share one or two alleles identical by state are truly identical by descent. This means that in return for a fairly modest reduction in power (because one is now dealing with a probability rather than a certainty of counting alleles that are iden-tical by descent) there is a halving in the amount of genotyping that needs to be done.

(20) In our own experience, the other advan-
tage of being able to make do without parental genotypes is that they are often difﬁ  cult to obtain in adult-onset disorders such as 
schizophrenia. Signiﬁ  cant regions of genetic linkage for disorders, 
notably schizophrenia, bipolar disorder, and autism that have been shown across different studies or found in pooled analyses have now been identiﬁ  ed. Another use of sib-pair methods is in study-
ing continuous traits (e.g. height, weight, personality test scores) to attempt to detect the quantitative trait loci that contribute to their heritability.
(14) One approach is to select probands who have 
extreme scores on some quantitative measure and investigate the extent to which marker allele sharing by siblings predicts the regres-sion to the population mean of the siblings’ scores.
(14) This has

(14) This has 
been successfully used in mapping a quantitative trait locus contrib-uting to reading ability in children. Unfortunately the drawback of such methods and of sib-pair linkage approaches generally is that they are only capable of detecting moderately large effects. This means that a quantitative trait locus contributing less than about 2.4.1 quantitative genetics

SECTION 2  the scientific basis of psychiatric aetiology 220
10 per cent of the variance, or a disease susceptibility locus confer-
ring a relative risk of less than 2, will probably require very large samples running into several hundreds, perhaps thousands, of pairs. If we assume that most common diseases and complex behaviours involve the combined action of many genes of small effect, complementary strategies based on allelic association are required.
In their classic form, allelic association studies are more straight-forward to carry out than linkage studies. A sample of cases affected by a disorder (or subjects who have scores higher than a given threshold on a quantitative measure) is compared with controls who do not have the disorder (or subject whose scores are near average). The frequency of alleles at the marker locus is then com-pared in the two groups. The signiﬁ  cance of the difference can then

be compared in the usual way for contingency table analysis using a χ
2 test (or Fisher’s exact test if expected frequencies are small). In 
addition to signiﬁ  cance it is useful to have a measure of the strength 
of association. A variety of statistics can provide this but probably the most useful and intuitively appealing is the relative risk , i.e. the 
proportion of cases among those carrying the marker allele or risk factor, P
1, divided by the proportion of cases among those not 
carrying the factor, P2. As we can calculate from Table 2.4.1.2, RR = 
P1/P2 = ( a/(a + b))/(c/(c + d)). If the disorder is uncommon, 
i.e. a and c are small relative to b and d, RR can be approximated 
by another, easier-to-obtain statistic, the odds ratio, OR = a × d/
(b × c). If a positive marker disease association has been found the 
odds ratio will be signiﬁ  cantly greater than 1.
Before the current era of molecular genetics many association

Before the current era of molecular genetics many association 
studies of disease with classical markers were carried out most notably with blood groups and with the HLA system. One of the earliest well-replicated ﬁ  ndings was an association between blood 
group O and duodenal ulcer. The odds ratio was less than 2 in most studies and Edwards
(15) pointed out that the proportion of vari-

ance in liability to the disorder explained by the association was only about 1 per cent. Even though later disease association studies on HLA, with other diseases such as type I diabetes and various auto immune disorders were stronger, it has been pointed out that here too only a small proportion of variance is accounted for. Although this could in one respect be considered disappointing, it demonstrates that allelic association can detect small gene effects in polygenic or multifactorial traits and may therefore prove to be more useful than linkage.
How does allelic association arise and what does its detection tell 
us? There are three principal mechanisms of association. The ﬁ  rst 
is linkage disequilibrium. Normally pairs of alleles at two different loci occur together no more often than would be expected by

is linkage disequilibrium. Normally pairs of alleles at two different loci occur together no more often than would be expected by 
chance (i.e. they are in ‘equilibrium’). In most cases this is the result 
of independent assortment. However, even if loci are linked they will usually approach equilibrium very rapidly with the proportion of associated alleles decreasing by 1 − θ each generation. Only 
where the two loci are very close together does disequilibrium tend to persist. For example, where the distance is 1 cM corresponding to a recombination rate of one meiosis in 100, the time taken for an

association to go half way to equilibrium is 69 generations. For a distance of 0.1 cM the time taken is 693 generations, or about 20 000 years. The second cause of association is when a polymor-phism within a gene itself has a functional effect which results in susceptibility to a disease. The third, and in most cases least inter-esting, phenomenon is population stratiﬁ  cation. This occurs where 
there has been recent admixture of populations or two or more ethnically distinct populations living side by side with little inter-breeding. If the populations differ in terms of the frequency of alleles of the genetic markers and in the frequency of the disease being studied, marker disease associations can arise if there is not careful ethnic matching of patients and controls.
Another way of overcoming stratiﬁ  cation is not to study unrelated

Another way of overcoming stratiﬁ  cation is not to study unrelated 
cases and controls but to study families and derive the controls ‘internally’ . The most familiar method in current use is the trans-mission disequilibrium test.
(16) This requires affected individuals 
to have at least one parent who is heterozygous at the test locus. The affecteds can therefore each receive one of two alleles from such parents. A 2 × 2 contingency table can then be constructed on whether a particular allele is the transmitted or the non-transmitted allele. This is illustrated in Table 2.4.1.3 for a marker with two alleles, A
1 and A2. The entries in each cell of the table, a,b,c, and d
are counts of the number of parents transmitting or not transmit-ting each allele to their affected offspring. The signiﬁ  cance of the 
transmission disequilibrium test is simply assessed by a McNemar χ
2 test.
Finally, it is becoming increasingly accepted to actually test for

2 test.
Finally, it is becoming increasingly accepted to actually test for 
population stratiﬁ  cation in the laboratory by examining whether 
random gene variants not thought to be involved in disease, differ in cases and controls. Assuming that stratiﬁ  cation can be overcome 
there are broadly two ways to proceed with association studies. The ﬁ rst is candidate gene association studies and the second is whole 
genome association studies.
(a) Candidate gene association studies
Functional candidate gene studies concentrate on polymorphisms in or near genes that encode for proteins that are likely to be involved in the disorder. This has so far been the commonest type 
of association study in psychiatry as in most other common dis-
eases, and there are some interesting early results relating to, for example, polymorphisms at the serotonin 5-HT
2a receptor gene in

2a receptor gene in 
schizophrenia(17) and the dopamine D4 receptor gene in attention-
deﬁ cit-hyperactivity disorder.(18) Positional candidate gene studies 
involve selecting genes that are in regions implicated by linkage. 
Table  2.4.1.2  Case-control  allelic association
Marker N affected N unaffected
Present ab
Absent cdTable  2.4.1.3  Transmission disequilibrium test: affected subjects 
with at least one parent heterozygous for allele A
Non-transmitted
Transmitted A1A2
A1ab
A2 cd
X2.1 df = ( b–c)2/(b + c)

221
This approach, ﬁ  ne mapping using association to narrow down a 
region discovered by linkage, has for example resulted in identiﬁ  ca-
tion of a susceptibility locus, KIAA0319 ,(19) involved in reading 
disability. Another positional strategy involves obtaining clues about the potential position of a susceptibility gene from individu-al families who present with a disorder and have a speciﬁ  c region of 
a chromosome disrupted. For example, a study of Scottish families with translocations involving a region on chromosome 1 and schizophrenia and bipolar disorder led to identiﬁ  cation of a sus-
ceptibility gene DISC1  for schizophrenia.
(20)
(b) Whole genome association (WGA) studies
The second approach, which has only recently become technically

(20)
The second approach, which has only recently become technically 
feasible, is to attempt a systematic search through the entire genome with the aim of detecting linkage disequilibrium or direct associa-tion. It follows from what we have discussed earlier that a genome-wide search for linkage disequilibrium or direct association has a particular attraction in the study of polygenic disorders in that it should be capable of detecting genes of small effect. Very high throughput genetic analysis involves hydridizing DNA into many thousands of oligonucleotides on microarrays and allows a very large number of biallelic single nucleotide polymorphisms (SNPs) to be tested very rapidly and at comparatively low cost. Cost can be reduced even further by performing the initial screening by DNA pooling. Such methods
(21) combine samples from groups of

(21) combine samples from groups of 
patients and groups of controls processing them in batches. Positive ﬁ ndings can then be followed up by doing individual genotyping. 
Thus if pools consist of say 100 individuals, the initial cost of geno-typing is reduced 100-fold. Against this, some information is lost by DNA pooling and accurate construction of pools is difﬁ  cult and 
time consuming. The problem of multiple testing can be overcome either (as in the DNA pooling approach), by carrying out a two-stage analysis with fairly liberal test criteria in the ﬁ  rst stage fol-
lowed by stringent criteria in the second stage, or by simply setting a very stringent criterion at the beginning. It has been shown for example that, even with an alpha level set at 1 × 10
–6, detection of 
linkage disequilibrium with genes of small effect is feasible with realistic sample sizes.
As we write, WGA studies are being completed using commer-
cially available microarrays containing 500 000 SNPs.

(22) Such 
studies present formidable challenges including the need for very large samples of subjects to provide adequate power of detection and problems of multiple testing and handling of huge amounts of data. Nevertheless, WGA studies have already led to the identiﬁ  ca-
tion of susceptibility genes for common non psychiatric disorders (e.g. macular degeneration and diabetes) and the initial results of several WGA studies of psychiatric disorders including schizophre-nia, bipolar disorder, and ADHD will soon be available or have already been published.
(23)
Molecular genetic studies investigating 
gene–environment interplay and intermediate phenotypes
Genetic variants do not necessarily confer risk for a psychiatric 
disorder unless in the presence of a speciﬁ  c environmental risk

disorder unless in the presence of a speciﬁ  c environmental risk 
factor. Molecular genetic studies allow a direct test of whether the association of a speciﬁ  c gene variant with disorder is contingent 
upon exposure to a speciﬁ  c environmental factor. There are a number of important methodological issues that need to be con-
sidered when investigating G × E.
(24) Most importantly, in testing 
for G × E, there is the problem of multiple testing given the poten-
tial for testing a large number of gene variants and environmental risk factors. Thus, there need to be good a priori  hypotheses before 
selecting a specific gene variant and environmental measure. Despite these caveats, there is increasing evidence of the likely importance of G × E in psychiatry as a number of ﬁ  ndings have 
now been replicated. The presence of G × E also provides one

now been replicated. The presence of G × E also provides one 
potential explanation (amongst others) for non-replication of genetic association ﬁ  ndings across different studies.
T o date the strongest evidence of G × E has been for a gene vari-
ant that affects MAOA enzymatic activity and which appears to increase the risk of antisocial behaviour only in the presence of childhood maltreatment.
(25) There is also evidence to suggest that 
possession of a gene variant that affects function of the serotonin transporter (5HTT) increases the risk of depression in the presence of life events.
(26,27)  A potentially clinically important type of G × E 
research is pharmacogenetics. Here the aim is to identify genetic variants that inﬂ  uence clinical response and the risk of side-effects 
upon exposure to speciﬁ  c types of medication. The hope is that 
such approaches may lead to a more individually tailored approach to prescribing.

As gene variants associated with psychiatric disorder are identi-
ﬁ ed, and variants that affect gene function recognized, there is an 
increasing need to identify the intermediate biological pathways and mechanisms. This has led to an increasing amount of research on potential intermediate phenotypes that may account for the link between risk factor and psychiatric outcome. Most interest to date has focused on measures of brain function and structure, assessed through imaging studies
(28) as well as neurocognitive, biochemical,

(28) as well as neurocognitive, biochemical, 
and physiological traits. For example, the functional variant in the 5HTT that is associated with depression in the presence of adverse life events appears to be associated with amygdala hyper-responsivity to stress. There is also some evidence that a functional COMT gene variant plays an important role in dopamine clearance in the prefrontal cortex and is associated with prefrontal cortical func-tioning, assessed through cognitive task performance and fMRI. It is hoped that this new era of imaging genetics together with other areas of neurobiological research will help elucidate the risk path-ways that lead from genetic and environmental risk factors to psychiatric disorder.
Kendler, K.S. and Prescott, C.A. (2006). Genes, environment and 
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The transformation of the LOD score (an acronym for log of the

The transformation of the LOD score (an acronym for log of the 
odds ratio), from obscurity as a footnote in medical genetics, to celebrity as multiple choice test item in professional examinations in psychiatry, epitomizes the invasion of genetics, and particularly molecular genetics into psychiatric research. Moreover, like other celebrities caught up in fast moving ﬁ  elds, LOD scores are likely to 
return to their humble origins within a few years. As molecular genetic approaches to mental health move away from simply iden-tifying genes and DNA sequence variants towards functional stud-ies of increasing complexity, newcomers to the ﬁ  eld have to master 
an expanding literature that covers diverse ﬁ  elds: from quantitative 
genetics to cell biology, from LOD scores to epigenetics. This chap-ter takes on the task of making the reader sufﬁ  ciently familiar with

genetics to cell biology, from LOD scores to epigenetics. This chap-ter takes on the task of making the reader sufﬁ  ciently familiar with 
the broad range of subjects now required to follow the progress of psychiatric genetics in the primary literature.
A number of achievements have to be highlighted. Foremost 
among these is the completion of the human genome project. Announced annually from 2001
(1–3) and thereby begging the ques-
tion as to what constitutes completion, the human genome project is now an essential biological resource. As expected, the ability to sequence whole genomes has transformed the way genetics is car-ried out, perhaps most egregiously with the rise of bioinformatics as a core discipline: discovery now takes place using the internet rather than the laboratory. Anyone with an interest in human biology should look at the frequently updated information at http://www.ensembl.org or http://genome.ucsc.edu.
Without the human genome two other critical developments

Without the human genome two other critical developments 
would have been impossible: the ability to analyse the expression of every gene in the genome and the ability to analyse (theoretically at least) every sequence variant. Both developments also depend on miniaturization technologies that enable the manufacture and 
interrogation of initially thousands and then millions of segments 
of DNA. In addition, results from the International Haplotype Map (HapMap) project,
(4) which catalogues common variation in 
the human genome have been crucial in making it possible to take apart the genetic basis of common, complex disorders such as depression, schizophrenia, and anxiety.

223
Few disciplines are more burdened with jargon than molecular 
genetics. This is partly due to the proliferation of molecular techniques, but it is also partly intrinsic to the subject; the only unifying principle is evolution, which often operates in a very ad hoc fashion. Biological solutions to the problems posed by selec-tion result in the adaptation of existing structures to new uses, rather than to the invention of purpose-built systems. Consequently there are few general lessons to be learnt and the novice simply has to become adept at recognizing the acronyms and neologisms that decorate the literature. The material in this chapter aims to equip the reader with the necessary terminology. It begins with the struc-ture and function of DNA, an essential starting place for a number of reasons.
Nucleic acid structure and function
The chemical constituents of genetic information are deoxyribo-nucleic acid ( DNA ) and ribonucleic acid ( RNA ). Both molecules

The chemical constituents of genetic information are deoxyribo-nucleic acid ( DNA ) and ribonucleic acid ( RNA ). Both molecules 
consist of linear chains of nitrogenous bases bound to a sugar (ribose) and a phosphate backbone. Because of the way the sugars are joined together, one end of each nucleic acid strand will have a terminal sugar residue in which the carbon atom at position number 5 of the ribose molecule is not linked; the other end has a free carbon atom at position 3. These two ends are termed the 5 ′
(5 prime) and 3 ′ (3 prime) ends respectively.
It is usual to describe a DNA or RNA sequence by writing the 
order of bases in a single strand, in the 5 ′ to 3′ direction. DNA con-
tains four nitrogenous bases: adenine (A), guanine (G), cytosine (C), and thymine (T). RNA differs in that it contains uracil instead of thymine.
Two structural differences between DNA and RNA are impor-

tant for understanding nucleic acid function. First, DNA has a hydroxyl group on part of its sugar constituent whereas RNA has a hydrogen atom. The result is that, in most biological environments, RNA is much more unstable than DNA. Second, RNA normally exists as a single molecule, whereas DNA is a double helix in which two strands are held together by weak hydrogen bonds between opposed base pairs ( bp), C joined to G and A to T. The sequence 
of one strand can therefore be inferred from the other. The two strands are said to be complementary to each other, and this prop-erty is exploited whenever DNA is copied (during meiosis, mitosis, orin vitro  processes such as ampliﬁ  cation of DNA using a polymer-
ase chain reaction).
As beﬁ  ts an unstable molecule, RNA mediates the expression of

As beﬁ  ts an unstable molecule, RNA mediates the expression of 
genetic information; its production and degradation are tightly controlled. RNA is translated into a linear order of amino acids in proteins according to a three-letter code (e.g. GAA encodes the amino acid glutamine). DNA acts as a template for the production of RNA in a process termed as transcription. But DNA is more than a stable repository of encoded protein sequence information; it also contains information that controls the transcription of RNA.
Disorders of the template function of DNA are the molecular 
basis of inherited dispositions and illness, and are the subject mat-ter of genetics. By contrast, gene expression (the transcription and 
translation of RNA) is not entirely genetically predetermined. It is highly regulated, but in response to changes in the cellular environ-
ment which in turn reﬂ  ect changes in the state of the organism.

ment which in turn reﬂ  ect changes in the state of the organism. 
Disorders of gene regulation are now emerging as important causes of disease.Genome organization
DNA within cells is packaged into chromosomes in the cell nucleus, with a tiny amount (16 569 bases containing 37 genes) in the mito-chondria. Since mitochondria in the fertilized egg are maternally derived, mitochondrial inheritance is through the female lineage. Although small, mitochondrial disorders contribute substantially to degenerative disorders including ageing. More important is nuclear DNA.
As of 2007, the size of the nuclear genome is 3 253 037 807 bp 
(3.3 gigabases) containing 21 662 known and 1064 novel genes (http://www.ensembl.org). Packing such a large molecule into a cell is done at a number of levels, with profound consequences for gene function. At the ﬁ  rst level, 147 bp lengths of DNA are wrapped

around octamers of proteins known as histones. These nucleo-somes are the fundamental units of the state of packaged DNA known as chromatin.
Packaged DNA is itself organized into 22 autosomal chromo-
somes, one inherited from the mother and one from the father, and two sex chromosomes, X and Y. Each chromosome pair exchanges stretches of DNA during sexual division (meiosis) in a process called recombination (without which genetic mapping, the basic method of finding disease genes, would be impossible). Chromosomes have three functional elements: origins of replica-tion, centromeres, and telomeres. Replication origins are required to initiate DNA replication and maintain chromosome copy number. Their molecular structure is unknown. Centromeres are responsible for the segregation of chromosomes during cell divi-
sion. Their molecular nature is also not understood, but they are visible in light microscopy as a constriction where the duplicated

sion. Their molecular nature is also not understood, but they are visible in light microscopy as a constriction where the duplicated 
chromosomes (called chromatids) are held together. Chromosomes are said to have two arms, separated by the centromere which, despite its name, is not always at the centre. Short arms are termed p (petit ) and long arms q ( queue ). T elomeres are the ends of chro-
mosomes and their molecular nature is well understood. They consist of long stretches of the sequence TTAGGG without which the chromosome is unstable, tending to break apart and fuse with itself or to other chromosomes.
No one has found any general principles that organize genetic 
material within chromosomes. Rather than being an efﬁ  ciently

material within chromosomes. Rather than being an efﬁ  ciently 
organized plan of the organism consisting of precise drawings, the genome resembles a working copy written over countless rough drafts and discarded versions, among which there are literally thousands of jottings and scribbles, most irrelevant to the ﬁ  nal 
structure. While there are examples of gene families clustered in the same chromosomal location (for instance genes involved in immune regulation are clustered on chromosome 6p), more com-monly the position of genes on chromosomes does not reﬂ  ect 
functional similarity. For example, genes expressed only in one tissue, or at one stage of development, are often immediately adjacent to widely expressed housekeeping genes.
Genes and the regulation of gene expression

DNA is transcribed into RNA, which in turn is translated into protein. Transcription involves the excision of large portions of transcribed RNA (by RNA splicing enzymes) and modiﬁ  cations 
to the ends of the RNA molecule (capping of one end and polyade-nylation of the other). The ﬁ  nal product, messenger RNA ( mRNA ), 2.4.2 molecular genetics

SECTION 2  the scientific basis of psychiatric aetiology 224
contains a central section, translated into protein, and ﬂ  anking 
non-coding regions. The consequence of these manipulations is 
that DNA and mRNA are not coterminous; sections of DNA 
that encode mRNA (termed exons) are interrupted by often very 
large stretches of DNA that are not translated (termed introns) 
(Fig. 2.4.2.1).
Gene expression is controlled in a number of ways , predominantly 
at the level of transcription (but posttranscriptional processing 
and translational control are important for some genes). While 
knowledge in this area is still rudimentary, but advancing fast, it 
has already led to new insights in disease aetiology: understanding 
theories of the neurobiology of depression now requires familiarity 
with chromatin remodelling; epigenetic effects are often invoked in 
molecular biology of intellectual disability. Below I summarize 
information about the relevant molecular processes.

1.Transcription factors:  transcription factors exercise control 
over gene expression. Transcription occurs when RNA polymer-
ases manufacture RNA from the template DNA, a process that 
requires the help of transcription factors, proteins that recog-
nize and bind to speciﬁ  c DNA sequences (note that transcription factors can also repress transcription). Although transcription 
factor-binding sites are found close to a gene, at a 5 ′ region 
known as the promoter (see Fig. 2.4.2.1), they may also be situ-
ated far away, sometimes within other genes. The characteriza-
tion of these control elements remains a major challenge for 
genome research and is currently a focus of the ENCODE 
project, a continuation of the human genome project whose

project, a continuation of the human genome project whose 
aim is the comprehensive identiﬁ  cation of all the functional ele-
ments in our genome (http://genome.ucsc.edu/ENCODE/).
 Transcription factors typically control the expression of a 
number of genes, reﬂ  ecting the presence of a hierarchical struc-
ture of coordinated gene expression. Consequently mutations in 
transcription factors have effects on different, seemingly unre-
lated phenotypes, a phenomenon called pleiotropy. The constel-
lation of phenotypic abnormalities seen in intellectual disability 
syndromes can be explained in this way. For example mutations 
in the X-linked ATRX gene result in an anaemia ( α-thalassae mia), 
a characteristic facial appearance, profound developmental 
delay, neonatal hypotonia, and genital abnormalities.(5) The gene

delay, neonatal hypotonia, and genital abnormalities.(5) The gene 
contains sequence motifs indicating that it belongs to a group of 
proteins that bind to chromatin and is involved in chromatin 
remodelling, discussed below.(6)
2.DNA methylation:  gene inactivation is associated with DNA 
methylation, predominantly the addition of methyl groups to 
cytosine bases. DNA methylation occurs almost always at CpG 
dinucleotides, and most CpGs in the genome are methylated.(7)
DNA methylation represses gene expression in two ways: ﬁ  rst, 
modiﬁ  cation of cytosine inhibits the association of some DNA-
binding factors with their DNA recognition sequences, and sec-
ond proteins that recognize methyl-CpG can repress transcrip-
tion from the methylated DNA. Methylation of DNA does not 
change the DNA sequence itself, as it is reversible, but the meth-

ylation status is maintained when cells divide. Consequently the 
change is referred to as epigenetic modiﬁ  cation.
 DNA methylation is critical for imprinting, a form of gene regu-
lation in which transcripts are expressed from only one of the 
two parental chromosomes. Although there are relatively few 
imprinted genes (about 60 are currently documented, although 
sequence features in the region of known imprinted promoters 
implicate 600) imprinting is an important phenomenon in 
neurobiology for three reasons(8): (i) There is evidence from 
studies of embryos that maternally expressed genes enhance 
and paternally expressed genes reduce brain size, indicating that 
at least some imprinted genes are likely to be involved in neu-
rodevelopment.(9) (ii) Disorders of imprinting are important in

rodevelopment.(9) (ii) Disorders of imprinting are important in 
intellectual disability syndromes: Rett syndrome, Prader–Willi 
syndrome, Turner syndrome, and Angelman syndrome.(10)
(iii) Imprinting is involved in X chromosome inactivation, 
the mechanism by which cells compensate for males having just 
one copy of the X chromosome while females have two.(11) The 
X chromosome contains a disproportionately high density of 
loci affecting cognition and since males always inherit their 
X chromosome from their mother, the presence of X-linked 
imprinted genes is believed to contribute to sexually dimorphic 
effects.
 The biology of imprinting is complex and not fully understood. 
In germ cells and in pre-implantation embryos, all methylation Fig. 2.4.2.1 At the top of the ﬁ  gure the organization of a gene in genomic DNA

In germ cells and in pre-implantation embryos, all methylation Fig. 2.4.2.1 At the top of the ﬁ  gure the organization of a gene in genomic DNA 
is shown. Unshaded boxes correspond to coding regions (exons) and the two 
shaded boxes correspond to control regions. The control region immediately 5 ′; of 
the ﬁ  rst exon, where transcription is initiated, is known as the promoter and often 
has a characteristic sequence composition. In almost all ubiquitously expressed 
genes (and in many tissue-speciﬁ  c genes) it is unmethylated, GC rich, and has a 
relative excess of the dinucleotide CpG. The region, which typically contains the 
ﬁ  rst exon as well as the promoter, is called a CpG island. The boundaries between 
exons and introns are called splice sites and are conserved; introns virtually 
always start with the sequence GT and end with the sequence AG. The entire 
genomic region is transcribed into a primary transcript (bold arrow) which is then

genomic region is transcribed into a primary transcript (bold arrow) which is then 
processed to excise the introns. Many human genes undergo alternative splicing 
to yield a number of different mRNA products. Mature mRNA is then translated 
into a protein product.

225
patterns are removed, and then re-established.(12) About half of 
identiﬁ  ed imprinted genes are clustered within imprinting cen-
tres (IC) which carry the allele-speciﬁ  c methylation marks estab-
lished at this developmental stage. Most maternally silenced imprinted genes are repressed by promoter methylation. No protein-coding imprinted gene has been found that is repressed by paternal methylation derived from the sperm (presumably because of active demethylation of the paternal genome). Importantly, paternal repression is achieved, at least in some cases, by using a transcript on the opposite strand (an antisense transcript). Promoter methylation of the antisense transcript (usually resulting from oocyte-derived methylation) represses its transcription and thus activates the protein-coding gene epi-genetically.
 Some evidence, obtained by examining females with a single

Some evidence, obtained by examining females with a single 
X chromosome (Turner syndrome females), indicates that imprinted genes on the sex chromosomes inﬂ  uence brain struc-
ture and function.
(13) Since the single X chromosome is inher-
ited from either the mother or father, it is possible to compare the effects attributable to a maternally or paternally imprinted chromosome. Maternally expressed X-linked genes have been reported to inﬂ  uence hippocampal development, while pater-
nally expressed genes inﬂ  uence the normal development of the 
caudate nucleus and thalamus in females. Using Turner syn-drome patients, Skuse and colleagues have suggested that a paternally expressed allele is associated with enhanced social–cognitive abilities.
(14) A similar observation has been found in a 
mouse model of Turner syndrome, lending weight to the view that imprinted genes are involved in cognitive processes.
(15)
3.Chromatin remodelling:  the nucleosome forms a barrier to

(15)
3.Chromatin remodelling:  the nucleosome forms a barrier to 
transcription, primarily because DNA has to be free of nucleo-somes for it to be accessible to transcription factors and the large complex of proteins that constitutes RNA polymerase. T o some extent the organizational information of where nucleosomes are positioned is embedded within DNA sequence, in a nucleosome code; but the nucleosome is not a static unit. It too has dynamic properties and exerts an effect on transcription. Furthermore, like methylation, the effects are heritable, providing a second form of epigenetic modiﬁ  cation to DNA (X inactivation also 
involves this form of epigenetic modiﬁ  cation).
 Histones (the proteins that constitute nucleosomes) are subject 
to a large number of modiﬁ  cations (acetylation, ubiquitination,

to a large number of modiﬁ  cations (acetylation, ubiquitination, 
methylation, ADP-ribosylation, and sumolation of lysine resi-dues; and phosphorylation of serines and threonines) of which two, lysine acetylation and methylation, have been most heavily studied. Histone modiﬁ  cations can inﬂ  uence each other and 
may also interact with DNA methylation, in part through the activities of protein complexes that bind modiﬁ  ed histones or 
methylated cytosines. These, and other proteins that remodel chromatin, control genes involved in the development and activ-
ity of the central nervous system.
 Chromatin remodelling has attracted attention as a possible 
mechanism for bringing about persistent change subsequent to an environmental stressor.
(16) Two examples are relevant.

Chromatin remodelling has attracted attention as a possible 
(16) Two examples are relevant. 
Meaney and colleagues have reported that heritable differences in stress reactivity in rats depend on variation in parenting, not variation in DNA.
(17) Adult offspring of mothers that show higher levels of licking, grooming, and arched-back nursing 
(high-LG-ABN) are less fearful and show more modest hypoth-alamic-pituitary axis responses to stress than offspring of ‘low-LG-ABN’ mothers.
(18) How are these maternal effects, or other 
forms of environmental programming, sustained over the 
lifespan of the animal?
 Variations in maternal care were found to alter the methylation

 Variations in maternal care were found to alter the methylation 
status of a promoter of the glucocorticoid receptor gene. Central infusion of a histone de-acetylase inhibitor enhanced histone acetylation of the glucocorticoid receptor promoter in the off-spring of the low-LG-ABN mothers. Analysis of the promoter showed that CpG dinucleotides were hypomethylated. In conse-quence, the maternal effect on hippocampal glucocorticoid receptor expression and the hypothalamic-pituitary axis response to stress were both eliminated.
(19) This ﬁ  nding sug-
gests that there is a causal relation between epigenetic modiﬁ  ca-
tions, glucocorticoid receptor expression, and the maternal effect on stress responses.
(20)
 Nestler’s group invoked chromatin remodelling as an explanation 
for the long-lasting behavioural change induced by antidepres-sants.

(20)
(21) Chronic defeat stress in rodents is reversed by chronic 
(but not acute) antidepressant treatment, a model for the action of antidepressant action in our own species. Chronic defeat stress and chronic antidepressant treatment are associated with recipro-cal, long-lasting changes in expression levels of brain derived neu-rotrophic factor (BDNF). This is in turn associated with lasting changes in chromatin architecture at the corresponding BDNF gene promoter. Furthermore, down-regulation of a histone de-acetylase (Hdac5) by chronic antidepressant treatment was necessary for the therapeutic efﬁ  cacy of the antidepressant.
4.Small RNAs:  small RNAs include micro RNAs (miRNAs) and 
small interfering RNAs (siRNAs) directly or indirectly alter gene transcription.
(22, 23) siRNAs, derived from double-stranded

(22, 23) siRNAs, derived from double-stranded 
RNAs (dsRNAs), control cleavage of other transcripts and can themselves direct the production of dsRNA by RNA-dependent RNA polymerase; they are also implicated in recruiting hetero-chromatic modiﬁ  cation that leads to transcriptional silencing.
 The extent of siRNA involvement in eukaryotic gene regulation 
is still unclear. Micro RNAs specify posttranscriptional gene repression by base pairing to the messages of protein-coding genes. They represent nearly 1–5 per cent of all genes in higher eukaryotes and have been implicated in developmental timing and neuronal patterning. They are believed to facilitate the tran-sition between developmental stages and therefore are likely to have an effect on the expression and evolution of most mam-malian mRNAs.
 Only 3 per cent of the genome codes for protein.

Only 3 per cent of the genome codes for protein.
(24) However, 
that is not to say that the remaining 97 per cent is inactive; in fact the number of transcripts is at least 10 times as great as the number of genes.
(25,26)  What this means in terms of function is 
not clear, but along with the discovery of small RNAs it has forced a re-evaluation of what is meant by a gene. The idea that a gene is a section of DNA transcribed into RNA, which in turn encodes a protein, fails to capture the gamut of RNA species, some of known function (such miRNAs), some with only suspected function. The emerging complexity of gene function and the multiple species that need to be included in any deﬁ  nition of a 2.4.2 molecular genetics

SECTION 2  the scientific basis of psychiatric aetiology 226
gene has dramatically increased our understanding of molecular 
pathogenesis.
Genetics and genotyping
Chromosomes are not stable structures. They rearrange during meiosis, recombining material between the paternal and maternal chromosomes. The mechanisms of recombination are not relevant for understanding neurobiology, but without recombination we would not be able to track mutations. This section describes the basic methodologies currently used. T o follow it, and the many reports in the literature, it is essential to be familiar with genetic terminology. A brief reminder is provided next.
A position on a chromosome is called a locus, a general term 
which can refer to a gene or a segment of DNA with no known function. DNA sequences that differ at the same locus are called allelic variants. Since we have two copies of each chromosome, by deﬁ nition we have two alleles at each locus. If these alleles are iden-

tical the individual is said to be a homozygote; if they are different, 
the individual is a heterozygote. It follows that for a locus with two alleles (that is one which is di-allelic, as are the single nucleotide 
polymorphisms that form the basis of almost all genetic mapping experiments), then there are three possible genotypes. For example, if the alleles are either C or T, the possible genotypes are CC, CT, and TT, whose frequencies in a population, in the absence of migra-tion, mutation, natural selection, and assortative mating, are a sim-ple function of allele frequencies (this phenomenon is termed Hardy–Weinberg equilibrium).
The relationship between alleles at different loci is important for 
genetic mapping. Assume there are two loci on the same chromo-some, separated by approximately 1 megabase (Mb). The loci are again di-allelic, the ﬁ  rst with alleles C and T, the second with alleles

A and G, so that there are nine possible two-locus genotypes: ATCC, TTCG, AAGG etc. Consequently, the chromosomes of an individu-al with the two-locus genotype ATCG could be any of the following four: A-C, A-G, T-C, or T-G. This combination of alleles along a chromosome is known as a haplotype. If recombination occurs between the two loci it will break-up the haplotype, so that the off-spring of someone with the haplotype A-C on one chromosome and T-G on the other may inherit the novel haplotype A-G. The probability at which this occurs depends on the genetic distance between the two loci. For 1 Mb in the human genome this proba-bility is approximately 1 per cent per meiosis, or 1 cM.
Molecular mapping depends on the availability of genetic mark-

ers across the genome. The genome is replete with DNA sequence polymorphisms whose only known use is to enable geneticists to map disease genes. On average, every 1000 bp will contain 1.4 bases that differ between two randomly chosen individuals, almost all of which have no phenotypic consequence. In addition, there are small runs of repeated sequence (most commonly CA) which differ in length between individuals. At least one of these short tandem repeats ( STR s), or microsatellites , is found every 50 kilobases ( kb)
and they also have no known phenotypic consequences. There are other more complex sequence polymorphisms, but single nucleotide polymorphisms ( SNP s) and microsatellites are the most 
useful for identifying disease genes.
Genotyping of genetic markers almost always starts by amplifying

Genotyping of genetic markers almost always starts by amplifying 
DNA using the polymerase chain reaction (PCR). PCR requires the following reagents: a DNA polymerase; a pair of oligonucleotides (also referred to as primers), which are synthetic single-stranded

DNA using the polymerase chain reaction (PCR). PCR requires the following reagents: a DNA polymerase; a pair of oligonucleotides (also referred to as primers), which are synthetic single-stranded 
DNA, usually between 15 and 25 bases long, complementary to two sequences on opposite strands of the target DNA; the target DNA itself; all four nucleotides, usually present in excess; appropri-ate buffer and cofactors for the reaction. The reaction proceeds in a cycle of three steps: (1) the mixture is heated to over 90°C for 1 min to separate the complementary strands of target DNA, (2) the mixture is cooled, to about 50°C, so that the oligonucleotides anneal to their complementary sequence in the target DNA and allow the DNA polymerase to bind (oligonucleotides are required to prime the polymerase), and (3) the temperature is adjusted to allow the polymerase to function in the extension component of 
the reaction. Typically the polymerase is from a thermophilic

the reaction. Typically the polymerase is from a thermophilic 
bacterium with a permissive temperature of 72°C. Products from the ﬁ  rst cycle serve as targets for a second round of ampliﬁ  cation 
and so on, for up to about 40 cycles.
The method used to genotyping the PCR product depends on 
the nature of the sequence variant. Microsatellite genotyping involves discriminating the length of the PCR products, usually accomplished by separating the fragments by electrophoresis, in which an electrical current causes smaller fragments to migrate more quickly than larger fragments through a matrix. Typically a ﬂ uorescent label is incorporated into the ampliﬁ  ed DNA allowing 
the PCR products to be detected by a laser, a method that allows automated analysis.
SNP genotypes can also be worked out from differences in

SNP genotypes can also be worked out from differences in 
molecular weight. For example, the nucleotide added to a primer complementary to sequence immediately preceding a SNP in the PCR fragment will depend on the genotype of the individual. The small difference between a primer with a C nucleotide added to its end (reﬂ  ecting the presence of a G nucleotide in the PCR fragment) 
compared to the same primer with the addition of a T nucleotide, can be determined using a mass spectrometer. However, most high-throughput genotyping methodologies (required for whole genome association studies) exploit the speciﬁ  city of DNA hybridi-
zation: while two complementary single strands of DNA stick (or hybridize) together (ATTGAC will anneal to TAACTG) a single base mismatch will prevent hybridization (ATTGAC will not anneal to ATAGAC). Consequently, a SNP can be detected by determining

whether primers hybridize to the PCR fragment. By labelling 
the primers, for example, with a ﬂ  uorescent dye, the hybridization 
can be visualized, and, using the same technology that builds com-puter semiconductors, millions of primers can be manufactured on a small piece of glass, allowing the simultaneous detection of millions of SNPs.
Genetic mapping: linkage and association
For genetic disorders that arise from a mutation in a single gene, behaving in a Mendelian fashion (dominant, recessive, or sex-linked inheritance), disease gene identiﬁ  cation is conceptually straight-

forward. Marker alleles follow Mendelian laws of segregation so that it is possible to determine if a marker is co-segregating with a disease in a family and to test the result statistically using methods described in Chapter 2.4.1. The expected result is an estimate of the probability that an allele and a disease locus will recombine; the lower the probability, the closer together the two loci are on the chromosome. The statistical test gives the likelihood that the esti-mate of recombination distance between a marker and a mutation

227
is correct. If the likelihood is acceptably high, then the next task is 
to reduce the genetic interval as much as possible and to identify a causative mutation. Access to the human genome makes it straight-forward to identify all genes within a given interval (go to one of the two websites mentioned above) and the ease of DNA sequenc-ing (many companies make this service available) makes it possible to screen candidates by a brute force approach: enough is known about sequence codes to recognize a mutation that will disrupt gene expression, and this can be experimentally veriﬁ  ed by looking 
at the production and structure of mRNA.
A good example of the success of gene mapping in pedigrees is 
the identiﬁ  cation of a mutation in the FOXP2 gene in a family that 
has a language disorder. The phenotype is complex, including both verbal and non-verbal cognitive impairments. However, the inher-itance pattern is straightforward: it ﬁ  ts a model in which a single

mutation in one copy of the gene is sufﬁ  cient to cause disease. By 
using markers from across the genome, a region on chromosome 7 was identiﬁ  ed that co-segregated with the defect and a mutation in 
a transcription factor, FOXP2, subsequently identiﬁ  ed.
(27,28)
Pedigree-based linkage works well when the disease follows 
Mendelian laws of segregation and has led to the identiﬁ  cation of 
many genes involved in intellectual disability and dementia. However, pedigree-based methods for disorders where the genetics does not ﬁ  t a simple Mendelian pattern have been much less suc-

cessful. The methods (described in Chapter 2.4.1) typically ask whether affected siblings in a family (usually just a pair) share the same allele at a locus: the more often sharing is observed, the closer the markers locus is inferred to be to the disease gene. The relative failure of the affected sibling pair strategy is almost certainly because of the small contribution that each locus contributes to disease susceptibility.
Neil Risch and Kathleen Merikangas pointed out in 1996 that if 
the genetic effect size attributable to a single locus is small (that is to say it would increase the risk of developing the disease less than two-fold) then the number of families required using a pedigree method would be impractically large.
(29) However, a direct test of

(29) However, a direct test of 
association between genetic marker and disease gene had much greater power. Simply by genotyping a marker and determining whether the distribution of genotypes was signiﬁ  cantly different 
between a set of unrelated cases and unrelated controls, small effects could be detected with relatively small sample sizes. The drawback was the need to test variants in every gene, possibly requiring researchers to genotype a million individual markers. Surprisingly, Risch and Merikangas showed that the objection to mounting such a study was not statistical, but technological.
Two advances made whole genome association studies feasible. 
First, as described above, technologies are available for genotyping on an appropriate scale. Second, an enormous catalogue of SNPs has been compiled. As of April 2007, 11 577 475 SNPs have been 
identiﬁ  ed and mapped on the human genome. Fortunately, not all

identiﬁ  ed and mapped on the human genome. Fortunately, not all 
these variants need to be genotyped for mapping disease genes. It was found that many SNPs were highly correlated with each other, because recombination is less likely to disrupt haplotypes of closely linked markers than of more distantly spaced markers (a phenomenon termed linkage disequilibrium (LD)). Consequently, aetiological variants can be expected to be in LD with one or more SNPs. By genotyping a carefully selected set of markers (called ‘tagged SNPs’) most of the common variation in the genome can be assayed. However, for this strategy to be practical, a haplotype map of the genome was ﬁ  rst required that catalogues the distribu-
tion of LD in different populations (since LD patterns are a prod-uct of population history, as well as of recombination distance). Genotyping on an immense scale in multiple populations was undertaken by the International Haplotype Map (HapMap) con-sortium,

(4) and the results, regularly updated, are available on the 
internet (http://www.hapmap.org).
The molecular basis of psychiatric disorders: 
Mendelian disorders
There are a number of conditions in psychiatry that arise from 
mutations in single genes (Mendelian mutations). As a rule, such disorders are rare and, importantly, they account for very few, if any, instances of common disorders: depression has never been attributed to a Mendelian mutation (though some single muta-tions, such as Huntington disease, do include a mood disorder in their phenotype). Nevertheless, rare single gene mutations can pro-vide important clues to the aetiology of more common conditions: for example, mutations in neuroligins, identiﬁ  ed as a rare cause of 
autism, suggest that the pathophysiology lies in abnormalities of synaptic function.
In general, the molecular basis of Mendelian mutations in psy-

chiatry is typical of other human genetic disorders in that they arise primarily from changes to one, or a few, nucleotides. These are 
described below under the heading point mutations. However, 
there are two exotica: triplet repeats and imprinting defects.
Point mutations
Changes in a single base pair (e.g. from C to T) of the coding sequence of the gene may alter the function of the protein ( mis-
sense mutations ), result in premature termination of the protein 
product ( non-sense mutations ), or create or destroy a splice site.

product ( non-sense mutations ), or create or destroy a splice site. 
In addition, deletions (of a single base pair or many megabases of DNA) and insertions (again of any size) disrupt transcription and translation of a gene. Deletions or insertions that do not affect a multiple of three bases alter the way that the message is translated and are known as frame-shift mutations. While none of these mech-anisms is special to psychiatric genetics, describing the mutational basis of a genetic disorder is an initial step in understanding how the disorder arises; what the DNA sequence change does to the pro-tein gives a clue to the protein’s function (if unknown) and to the pathogenesis of the condition. Analysis of mutants causing demen-
tia, isolated by positional molecular cloning, are an example.
The presenilins are ubiquitously expressed transmembrane

The presenilins are ubiquitously expressed transmembrane 
proteins in which mutations give rise to about 40 per cent of famil ial 
Alzheimer’s disease.
(30) More than 160 mutations in the presenilin 
genes have been identiﬁ  ed. Almost all are mis-sense mutations. 
Why are there no frame-shift or non-sense mutants? Mis-sense mutants alter an amino acid in the protein and therefore can alter its function. One clue about the nature of the functional change comes from looking at where mutations occur within the protein, thereby discerning whether some parts of the molecule are more frequently involved than others. The distribution of mutations in the presenilins is indeed non-random; mutations occur at resi-dues which are the same in both presenilin genes, lying on one side of the α helix in transmembrane domains, predominantly in 
exon 8. Thus the mutational spectrum highlights key residues for 2.4.2 molecular genetics

SECTION 2  the scientific basis of psychiatric aetiology 228
understanding the protein’s functions.(31, 32) The mutations in 
presenilin result in a gain of function: they alter the ratio of the two forms of amyloid that constitute neuritic plaques, one of the histo-logical hallmarks of the Alzheimer’s disease.
(33, 34)
Where a gene’s function is known, the distribution of mutations 
may reveal the likely pathogenesis. For example, mutations in the tau gene cause frontotemporal dementia with Parkinsonism (Pick’s disease).
(35, 36) The most common mutation occurs in the 5 ′ splice 
site of exon 10, resulting in overproduction and accumulation of one form of tau; mutations in other regions of the gene lead to accumulation of a different form of the protein. The position of the mutations in tau indicate that they cause disruption of tau micro-tubule binding, which may cause cell death by the degeneration of microtubules or through an increase in unbound tau.
Triplet repeats

One mutational mechanism is unusual and deserves special com-ment: expansion of trinucleotide repeats.
(37) Its importance in psy-
chiatry is that it occurs in at least 16 neurological disorders, some with behavioural phenotypes (such as Huntington disease). No one knows why trinucleotide repeat expansions tend to be found in disorders of the central nervous system. The mechanism was ﬁ  rst 
discovered in 1991 as the cause of fragile X syndrome,
(38, 39) a com-
mon form of inherited X-linked intellectual disability.
The mechanism is important because it explains some otherwise 
unusual features of the phenotype. Table 2.4.2.1 lists the diseases associated with triplet repeats. At each locus there is a normal range of copy numbers above which the repeat array becomes unstable: 
the larger the number of copies, the more unstable the allele and in

the larger the number of copies, the more unstable the allele and in 
general the more severe the disease. Repeats increase and decrease in size both in somatic and germ line tissues, with two important consequences. First, it may not be possible to infer the severity of the condition from a blood test, since the repeat length in the brain may not be the same as in the lymphocytes (this is an example of somatic mosaicism). Second, as the repeat length increases in suc-cessive generations, the age of onset may decrease (this is called anticipation). For instance the age of onset of myotonic dystrophy ranges from birth to adulthood.
Genomic rearrangements and gene dosage effects
A number of disorders, primarily those associated with intellectual disability, have been found to be due to chromosomal rearrangeme nts. 
Down syndrome (trisomy 21) is by far the most common, account-ing for about a third of all cases with moderate to severe retarda-tion.

(40) Chromosomal rearrangements can be extremely complex, 
like the nomenclature used to describe them.
Abnormalities of the number of chromosomes result in aneuploidy. 
Deletion of part or an entire chromosome is termed a monosomy (or haploinsufﬁ  ciency); an extra copy of either part of or an entire 
chromosome is called trisomy. A general term to describe either loss or excess of chromosomal material is aneusomy. Most chro-mosomal abnormalities involve small regions of aneusomy and consequently are known as segmental aneusomy syndromes or contiguous gene syndromes.
(41)
Table 2.4.2 .1 Triplet repeat diseases
Disease Repeat unit Gene Normal repeat Expanded repeat Mechanism
Fragile X syndrome FRAXA (CGC)n FMRP 6–60 >200 Loss of function

(41)
Fragile XE syndrome FRAXE (CCG)n FMR2 4–39 200–900 Loss of functionFriedrich ataxia FRDA (GAA)n Frataxin 6–32 >200 Loss of functionMyotonic dystrophy type 1 DM1 (CTG)n DMPK 5–37 50–10 000 RNA-mediatedMyotonic dystrophy type 2 DM2 (CCTG)n ZNF9 10–26 >75 RNA-mediatedFragile X–associated tremor ataxia 
syndrome FXTAS (CGG)n FMR1 6–60 60–200 RNA-mediated

Huntington disease HD (CAG)n Huntingtin 6–34 36–121 Polyglutamine expansionSpinocerebellar ataxia SCA1 (CAG)n Ataxin1 6–44b 39–82 Polyglutamine expansionSpinocerebellar ataxia SCA2 (CAG)n Ataxin2 15–24 32–200 Polyglutamine expansionSpinocerebellar ataxia SCA3 (CAG)n Ataxin3 13–36 61–84 Polyglutamine expansionSpinocerebellar ataxia SCA6 (CAG)n CACNA1A 4–19 10–33 Polyglutamine expansionSpinocerebellar ataxia SCA7 (CAG)n Ataxin7 4–35 37–306 Polyglutamine expansionSpinocerebellar ataxia SCA17 (CAG)n TBP 25–42 47–63 Polyglutamine expansionSpinobulbar muscular atrophy SBMA (CAG)n Androgen receptor 9–36 38–62 Polyglutamine expansionDentatorubral-pallidoluysian atrophy DRPLA (CAG)n Atrophin 7–34 49–88 Polyglutamine expansionSpinocerebellar ataxia SCA8 (CTG)n SCA8 16–34 >74 UnknownSpinocerebellar ataxia SCA10 (ATTCT)n 10–20 500–4500 UnknownSpinocerebellar ataxia SCA12 (CAG)n PPP2R2B 7–45 55–78 UnknownHuntington disease-like 2 HDL2 (CTG)n Junctophilin 7–28 66–78 Unknown

229
The distribution of rearrangements in the genome is not random, 
reﬂ ecting instead the involvement of higher-order architectural 
features.(42) Regions susceptible to rearrangement are frequently 
ﬂ anked by, or contain, region-speciﬁ  c repeat sequences, or low-
copy repeats. In general, recurrent rearrangements, or those of 
common size and having clustered breakpoints, most frequently result from homologous recombination between repeats.
(43)
Chromosomal rearrangements in psychiatric patients other than 
those with intellectual disabilities are rare, but their occurrence has led to some important discoveries. Deletions on the end of chromosome 22q cause a syndrome that includes a psychosis often indistinguishable from schizophrenia, thus prompting an intense investigation of this region of the genome.
(44) Characterization of 
patients with translocations and psychosis also led to the identiﬁ  -
cation of a gene called DISC1 (for disrupted inschizophrenia)(45)

and screening for chromosomal rearrangements in patients with 
T ourette’s syndrome led to the identiﬁ  cation of mutations in a Slit 
and Trk-like family member 1 (SLITRK1) gene.(46)
The phenotypes of chromosomal rearrangements are thought to 
arise because of the loss, in the case of monosomy, or addition, in the case of trisomy, of dosage-sensitive genes, of unrelated func-tion, that happen to lie next to each other on the chromosome. However this is not always the case, as the examples of Prader–Willi syndrome and Angelman syndrome show.
Imprinting defects
A number of diseases can be attributed to a failure to establish, maintain, or recognize methylation. Rett syndrome is a progressive 
neurodevelopmental disorder that occurs almost exclusively in females, with an incidence of between 1/10 000 and 1/15 000 live births.

(47) Most females with Rett syndrome are usually hetero-
zygous for a de novo  mutation in methyl-CpG-binding protein 
MeCP2, a protein that induces the re cruitment of protein complex-
es involved in histone modiﬁ  cations and chromatin remodelling. 
Prader–Willi syndrome and Angelman syndrome are both caused by loss of function of imprinted genes on the proximal long arm of human chromosome 15.
(48) Prader–Willi syndrome occurs 
if the paternal chromosome 15 is missing, Angelman syndrome if the maternal. In a few per cent of patients the disorder is due to aberrant imprinting and gene silencing.
Non-coding RNA

The discovery that small RNA molecules regulate gene expression has occurred too recently for us to know the importance of mutations in this system as a cause of disease. Examples are however beginning to be reported: a point mutation was shown to create a new promoter, 
driving a novel transcript that in turn silenced a neighbouring 
gene.
(49) There is one example from neuro psychiatric genetics, in 
which mutations in the binding site for microRNA hsa-miR-189 have 
been identiﬁ  ed as a cause of T ourette’s syndrome.(46) These complex 
mechanisms are difﬁ  cult to detect without a detailed understanding 
of gene regulation, which is likely to come in future years.
complex disorders
Genetic attempts to dissect common psychiatric conditions have

Genetic attempts to dissect common psychiatric conditions have 
been very slow to yield robust results. For every paper that reports a positive association between a genetic variant and schizophrenia, 
anxiety or alcohol abuse, another can be found that fails to replicate 
the ﬁ  nding.(50) There are at least three explanations for the difﬁ  cul-
ties in arriving at agreement. One is that scientiﬁ  c journals afford 
more importance to positive than negative results; for example, 
there have been more than 40 studies investigating the relationship between a variant of the dopamine D2 receptor and alcohol abuse. By plotting the effect size of each study against the year of publica-tion, a clear and statistically signiﬁ  cant negative correlation is 
found: studies with the largest effects are published first.
(51)

(51)
Publication bias almost certainly exists in other studies, but has rarely been systematically examined.
Second, a number of commentators have pointed out that the 
sparse success of genetic linkage and association studies in complex traits can be explained by the low power of individual studies.
(52)
Meta-analytic techniques that make it possible to combine data from many individual studies have revealed that the odds ratios attributable to individual susceptibility loci are commonly less than 1.3.
(53) Analysis of obesity, Type 2 diabetes and breast cancer 
shows that it is possible to obtain association results that replicate, but that tens of thousands of subjects are required.
(54,55) There is 
no reason to believe that psychiatric disorders will be any different in this respect; it is simply that no study has reported data from enough cases.
A third reason for the inconsistencies is that interaction between

A third reason for the inconsistencies is that interaction between 
genes can obscure the signal attributable to the main effect of the locus.
(56) Gene interaction, or epistasis, means that the phenotype 
depends on the allelic conﬁ  guration of a number of loci. For example, 
if there are two alleles ( i and j) at a susceptibility locus on chro mosome 
1 and two alleles at a susceptibility locus on chromosome 2 ( l and m)
then in an epistatic interaction disease will only manifest in those individuals with allele i on chromosome 1 and allele m on chromo-
some 2. Imagine a population in which allele i on chromosome 1 is 
common. Genetic association tests of the effect of allele m on chro-
mosome 2 will detect an effect. But the same test, when carried out in a population where allele i is rare, will not detect an effect, even though 
allele m is present at equivalent frequencies in both populations.
Epistasis is suspected to be important, but there are currently no

Epistasis is suspected to be important, but there are currently no 
well-documented examples in psychiatric genetics. More attention, and more information, is available for a similar phenomenon 
called gene by environment interaction (GXE). Interaction between 
genes and environment is said to occur if disease manifests only when speciﬁ  c alleles are exposed to a given environment. For exam-
ple, individuals with one allele (called s (for short)) at the promoter 
of the serotonin transporter may have an increased chance of developing depression, but only if they have been exposed to stressful life events.
(57) Individuals with the l (for long) allele are

(57) Individuals with the l (for long) allele are 
protected against the effect of this environmental stressor and are less likely to become depressed. GXE hides genetic association in the same way as epistasis. In the presence of GXE, unless differences in the environmental stresses experienced by subjects are taken into consideration, contradictory results may be obtained from testing a genetic association between the serotonin transporter polymor-phism and depression in different populations.
The advent of whole genome association studies applied to large 
case-control cohorts is beginning to unravel the molecular basis of common complex diseases. These studies are proving to be success-ful, in that they are identifying small numbers of loci that can be replicated in independent samples. However, since most studies 2.4.2 molecular genetics

SECTION 2  the scientific basis of psychiatric aetiology 230
ﬁ nd at best a handful of loci contributing to disease susceptibility, 
the results show that the bulk of the genetic predisposition to com-plex disease is almost certainly due to loci with much smaller effects than those found to date. There are also indications that many of the variants will be extremely rare, possibly even private to indi-vidual families.
One important indicator of the importance of rare variants is

One important indicator of the importance of rare variants is 
the poor coincidence between the location of whole genome association hits and those from linkage studies. It is important to bear in mind that linkage and association are detecting different signals: linkage will detect an effect when there are multiple differ-ent variants in the same gene (allelic heterogeneity). However, allelic heterogeneity dramatically reduces the power of genetic association, so that signals will be missed. Re-sequencing of genes has also led to a greater appreciation of the role of rare variants. Although individually rare, non-synonymous sequence variants in certain genes are cumulatively frequent and are known to inﬂ  uence 
quantitative traits, such as plasma lipoprotein levels
(58); it may 
prove to be true also for behavioural phenotypes.
Finding rare non-synonymous variants in genes should not

Finding rare non-synonymous variants in genes should not 
obscure the importance of aetiological variants that lie outside genes. It had been thought that the spectrum of sequence variants in complex disease would be similar to mutations found from the analysis of Mendelian conditions: that is to say variants in the cod-ing regions of genes, the splice sites, or the promoters. However, SNPs with robust, replicated results for association with complex disease are usually found nowhere near coding regions; they are located outside genes, in regions not known to have any function. Furthermore, when genes implicated by genetic association in psy-chiatric disease have been entirely sequenced, no obvious abnor-malities are seen. This is true, for example, of the genes believed to be involved in schizophrenia (dysbindin and neuregulin).

Genome-scanning technologies have also uncovered an unex-
pectedly large amount of structural variation in the human genome, including deletions, duplications, and large-scale copy-number variants, as well as insertions, inversions, and translocations. A global survey of copy-number variants identiﬁ  ed 1447 regions, covering 
360 Mb (a remarkable 12 per cent of the genome), revealing a con-siderable contribution to overall genetic heterogeneity.
(59) Critically, 
these variants were found in supposedly disease-free populations. It is possible that copy-number variants play an important part in the aetiology of common psychiatric disorders. For example, genome-scanning of autism has found copy-number variants in 10 per cent of cases of sporadic autism and in only 1 per cent of controls.
(60)

(60)
The armamentarium of molecular genetics tools wielded in the onslaught on the genetic basis of psychiatric disorders is impres-sive, expensive, and at the same time relatively uninformative about the neurobiology of the illnesses. As genes are identiﬁ  ed an equally 
complex technology is being applied to working out what those genes do. The last section of this chapter provides a guide to the relevant molecular biology.
One of the most fruitful ways of investigating gene function is 
through genetic manipulation of animals, for example, by intro-ducing a copy of the gene into a mouse or mutating the mouse version of the gene. Both approaches work because exogenous DNA can integrate into chromosomes. If the site of integration can 
be targeted, rather than being random, the exogenous DNA can be used to create mutations in speciﬁ  c genes.
Transgenic mice are made by injecting DNA (usually, but not

Transgenic mice are made by injecting DNA (usually, but not 
necessarily, human) into fertilized mouse oocytes. Integration is a rare and random event and almost always involves multiple copies entering at a single site, making interpretation of some transgenic experiments difficult. More specific genetic manipulation is achieved by exploiting homologous recombination in embryonic stem ( ES) cells. DNA containing a mutated copy of the gene of 
interest in tandem with a selectable marker (e.g. an antibiotic resist-ance gene) is introduced into ES cells. In a small number of cases the exogenous DNA recombines with, and consequently replaces, the cell’s copy of the gene. ES cells are isolated from embryos and can be grown in ﬂ  asks while retaining the potential to develop

into any tissue. Once they have been genetically manipulated and re-injected back into a pregnant mouse, the resulting embryo is a mixture of mutant and normal cells. If some of the ES cells contribute to the germ line of the embryo, then its offspring will be heterozygote mutants, from which homozygotes can be bred.
One important reservation should be borne in mind when 
assessing studies that have used gene targeting: the genetic back-
ground of a mutant can have an effect on the mutant.
(61) Most tar-
geting experiments use the ES stem cells derived from substrain 129 mice, which are crossed with another inbred line. The choice of inbred line into which the mutation is bred can be critical because many inbred lines have speciﬁ  c behavioural phenotypes; 
for instance, the inbred strain DBA/2 shows poor hippocampal-dependent learning and C57BL/6 mice are poor avoidance learners.
(62)
Improvements in knockout technology have had a major impact

(62)
Improvements in knockout technology have had a major impact 
on neurobiology. Rather than simply knockout genes, homologous recombination can be used to change part of a gene, for example, by substituting one amino acid to another, a process referred to as a knock-in technology. The development of binary systems, where two engineered lines are crossed, has given experimenters remark-able control over gene expression: genes can now be turned on, or off, by feeding the animal a compound that penetrates to the cell nucleus, such as tetracycline.
(63) The tetracycline transactivator 
(tTA) is used as a transcriptional switch to drive the expression of a gene of interest. The tTA system requires the use of two lines of transgenic mice. In one line the expression of the tTA protein is driven by a tissue or cell-type-speciﬁ  c promoter; in the second, a

gene of interest is placed downstream of the tet operator (tetO) and a promoter. The tTA protein binds to the tetO sequence and induces transcription. However, when the tetracycline is present, it binds to tTA and prevents it from binding to tetO and this halts transcription.
Binary systems also make it possible to generate mutations that 
are restricted to speciﬁ  c cell or tissue-types. This is done by intro-
ducing sequences recognized by an enzyme, cre recombinase,on either side of the gene of interest. Cre is a site-speciﬁ  c DNA 
recombinase derived from a bacteriophage that recognizes 34 bp 
sequences termed loxP sites. Cre catalyses the deletion of DNA 
ﬂ anked by a pair of loxP sites (the DNA is said to be ﬂ  oxed). Again 
the experimental system requires two lines: in one the gene of inter-est is ﬂ  oxed; in the other, cre is driven by a tissue-speciﬁ  c promoter

the experimental system requires two lines: in one the gene of inter-est is ﬂ  oxed; in the other, cre is driven by a tissue-speciﬁ  c promoter 
so that its expression is restricted to the cells of interest. Consequently, the gene is only deleted in that subset of cells.

231
Targeted homologous recombination, combined with condi-
tional control, has proved so successful a method for investigating gene function, that three major mouse knockout programmes are underway worldwide, working together to mutate every gene in the mouse genome using this technology. I have chosen a few examples on the application of the technology to illustrate the remarkable power of the approach and reveal why it has generated such inter-est in the neuroscience research community.
One of the earliest was the genetic demonstration of the effect of 
a brain-subregion-restricted NMDA receptor knockout on spatial memory.
(64) Following the discovery that high-frequency stimula-
tion of the hippocampal input ﬁ  bres can result in long-lasting

tion of the hippocampal input ﬁ  bres can result in long-lasting 
enhancement of synaptic transmission, long-term potentiation (LTP) has been subject to extensive investigation. The induction of LTP is blocked by amino-phosphonovaleric acid (AP5), an antago-nist of the NMDA subset of glutamate receptors. A voltage-dependent magnesium block and high calcium permeability mean that the receptor can be opened by glutamate only when the postsynaptic neurone is depolarized, thereby allowing the receptor to function as a detector and integrator of coincident activity at the synapse. Unsurprisingly, the demonstration that infusion of AP5 into the ventricles of rats impaired spatial learning generated intense inter-est in the potential role of the NMDAR as a crucial component of memory. Furthermore, since disorders of working memory have

been documented in schizophrenia, NMDAR dysfunction has 
attracted the attention of psychosis researchers. The genes encoding the receptor were identiﬁ  ed in the early 1990s. There are seven 
subunits (NR1, NR2A–D, and NR3A and B), of which the NR1 subunit is the only one that is indispensable for the formation of a functional receptor.
Functional investigation of the NR1 receptor using gene knock-
out technology proved to be impossible because NR1-knockout mice do not survive for more than a day after birth: the receptor has a crucial role in the midbrain for breathing. This is a general problem with constitutive knockout technology: lethality before, or just after birth is common. T onegawa and colleagues used the conditional technology to get over this problem. They ﬂ  oxed the 
NR1 receptor and crossed the mouse to a line in which cre recom-binase was under the control of a promoter of a gene expressed in the hippocampus.
(65) Because the recombinase was predominantly

(65) Because the recombinase was predominantly 
active in the CA1 region of the hippocampus, the NR1 gene could be knocked out postnatally in CA1 pyramidal cells.
The mouse strain had apparently normal growth and was 
fertile, but was severely impaired in a test of spatial learning.
(65)
Furthermore, recording of neuronal activity indicated a loss of coherent spatial representation in the hippocampus.
(66) The condi-
tional knockout provided strong evidence that NMDAR activity and NMDAR-dependent synaptic plasticity in the hippocampus are crucial for spatial learning. The importance of CA1 NMDARs in the acquisition of hippocampus-dependent memory was subse-quently extended to various non-spatial tasks, including recogni-tion of novel objects, and fear conditioning.
Advances in genetic engineering have also been critical in shap-

ing views of the neurobiology of anxiety and depression. There are a large number of publications reporting anxiety phenotypes asso-ciated with constitutive knockouts, implicating so many genes that as one reviewer points out ‘the overall message one takes away from these studies is that normal anxiety requires normal neuronal func-tioning. Disrupt such functioning in any of a number of different ways and anxiety-like behaviour is likely to be disrupted—not a 
very speciﬁ  c or informative conclusion’ .
(67) Application of the more 
focused molecular technology has been more informative.
Benzodiazepines bind the α-subunit of the pentameric receptor, 
enhancing the efﬁ  cacy of GABA in activating the receptor. By intro-
ducing a histidine to arginine mutation into the genes encoding 
each of the α1, α2, and α3 subunits and by testing mutants for

each of the α1, α2, and α3 subunits and by testing mutants for 
behavioural abnormalities, it has been possible to determine that theα2 isoform is responsible for the anxiolytic effects, but not the 
sedative or amnesic, effects of benzodiazepines in mice.
(68–70) These 
results have encouraged a search for isoform-speciﬁ  c medications, 
since a drug speciﬁ  c for the α2 subunit might reduce anxiety while 
having little or no sedative effects.
The importance of developmental, as well as tissue-speciﬁ  c 
effects, has also emerged from the use of conditional knockouts. While knockouts of the 5-HT1A serotonin receptor indicated the importance of this gene in anxiety, the mechanism by which it exerts an effect was not appreciated until Hen and colleagues devel-oped a tissue-speciﬁ  c, inducible rescue of the 5-HT1A knock-
out.

out.
(71) A mutant line, in which the 5-HT1A promoter was replaced

with a tTA responsive element, was crossed with a line in which the tTA protein was under the control of a promoter expressed in the hippocampus and cortex (the CaMKII promoter). The tTA protein induced expression of the 5-HT1A receptor in postsynaptic target tissues, but not in the serotonergic neurones of the dorsal raphe nucleus. Rescue of the knockout restored normal anxiety-like behaviour, demonstrating that the lack of postsynaptic receptors, rather than presynaptic, causes the anxiety phenotype. Furthermore, by giving tetracycline only during adulthood, so that the 5-HT1A receptor was expressed only during development, it was found that the mice behaved like wild type animals. By contrast, when 5-HT1A receptor expression was ablated during development, it was not possible to rescue the phenotype in the adult, demonstrating that stimulation of postsynaptic 5-HT1A receptors during a develop-mental critical period is required to establish normal patterns of anxiety-like behaviour

the phenotype in the adult, demonstrating that stimulation of postsynaptic 5-HT1A receptors during a develop-mental critical period is required to establish normal patterns of anxiety-like behaviour that then persist into adulthood.

The creation of knockouts should not obscure an equally impor-
tant application of molecular genetic methods in neuroscience: to augment existing functional tools or to create entirely novel ones. The developments can be categorized into visualization tools and, more recently, tools for intervention.
The ability to visualize proteins in cells has transformed cellular 
neurobiology. Visualization is made possible by attaching a ﬂ  uores-
cent tag, usually green ﬂ  uorescent protein or one of its congeners, 
to the DNA encoding the relevant protein. The genome projects have made available complete libraries of cloned DNA, so that it is possible to obtain cloned DNA of any gene. By using homologous recombination in bacteria, any gene can be tagged, and then inserted into the mouse genome, either by targeting or random transgenesis.
(72, 73) This genetic tagging has made it possible to

(72, 73) This genetic tagging has made it possible to 
track gene products spatially and temporally at the highest level of resolution (ﬂ  uorescently tagged genes expressed in the mouse brain 
can be seen at http://www.gensat.org). One immediate application of this technology is the identiﬁ  cation of sequences that confer tissue-
speciﬁ  c gene expression, revealed by the expression of the ﬂ  uores-
cent protein. Genes expressed in a speciﬁ  c brain region can then be 
replaced, rather than tagged, making it possible to target proteins to brain regions.
(74) This is one of the key technical requirements 
for mounting an interventionist approach to neurobiology.2.4.2 molecular genetics

SECTION 2  the scientific basis of psychiatric aetiology 232
Interventionist tools are set to transform neurobiology from a 
discipline in which function is inferred by observing the connectiv-ity of the nervous system, into one in which a function can be 
directly tested by activating its component parts. Sensor proteins, 
that detect changes in the physiological states of neurones through the emission of light, and actuator proteins that effect such changes in response to an exogenous signal, can be genetically engineered and inserted into organisms using genetic targeting technolog ies.
(75,76)
The ability to activate specific cell types through genetically

(75,76)
The ability to activate specific cell types through genetically 
encoded sensors responsive to light will undoubtedly facilitate the exploration of neuronal circuits. These techniques, though still in their infancy and currently most useful in invertebrate model organisms, are likely to have broad applications in neurobiology and will be a critical tool for understanding the function of genes involved in psychiatric disease.
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75. Lima, S.Q. and Miesenbock, G. (2005). Remote control of behavior 
through genetically targeted photostimulation of neurons. Cell,
121, 141–52.
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induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2. Neuron ,54, 205–18.2.4.2 molecular genetics

2.5
psychological science
Contents
 2.5.1 Developmental psychology through 
infancy, childhood, and adolescence
 2.5.2 Psychology of attention
 2.5.3 Psychology and biology of memory
 2.5.4 The anatomy of human emotion
R. J. Dolan
 2.5.5 Neuropsychological basis of neuropsychiatry
2.5.1 Developmental 
psychology through infancy, childhood, and adolescence
The child is father to the man. This saying seems so obviously true 
that it may surprise some people that it needs to be analysed and certain assumptions inherent in it need to be challenged if psy-chiatric practice across the lifespan is to be properly informed by ﬁ ndings from developmental psychology. This chapter examines

different conceptualizations of children and childhood through the ages and the ideas and theoretical models that have shaped popu-
lar, as well as professional, views on how children develop. It notes that there are no overarching theories of child development, but rather a pot-pourri of smaller models, most of which address disparate aspects of development.
Developmental psychology is not just about charting the norms 
of development, although knowledge of such is essential in all clin-ical practice. Rather, there are many issues that need to be critically examined in trying to understand how individuals develop. Taking a developmental perspective is about integrating this knowledge and understanding the patient’s presenting problems within such a framework.
The signiﬁ  cance that the clinician will place on a particular 
piece of behaviour will depend not only on the child’s socio-cultural background, but also on the child’s developmental age. Cox and Rutter

(1) note four reasons for taking a developmental 
perspective:
1 Children behave differently at different ages. The clinician must 
be familiar with the range of behaviours and their age-appro-priateness in separating the normal from the abnormal. For instance, simple consonant substitutions are widespread in the speech of pre-school children, but indicate some delay or devia-tion in the speech of teenagers.
2 Many aspects of behaviour can be viewed as progressing through 
a normal sequence. Admittedly, discrete stages are over-
emphasized by stage theorists such as Freud, Piaget, and Bowlby,

emphasized by stage theorists such as Freud, Piaget, and Bowlby, 
whereas the continuities in development are more emphasized by social-learning theorists such as Staats, Bijou, and Baer. Either way, an understanding of the normal sequences and ages permits a judgement as to whether the child has deviated in his or her development.
3 Different stages of development are associated with different 
stresses and different developmental tasks. Bladder and bowel training are normally achieved between the ages of 2 and 4 years. Major stresses on the child or the family at the time may interfere with the achievement of proper bladder and bowel control. Mood swings are very common in adolescence, making it difﬁ  -
cult to diagnose the severity of depression at this stage.
(2, 3)
4 An understanding of the processes which underlie both normal

(2, 3)
4 An understanding of the processes which underlie both normal 
and abnormal development will help in the understanding of how the problems have arisen.
(4) Such an historical perspective 
can help explain to the parents why a particular problem devel-oped, as well as give possible clues for future programmes for prevention. A major implication of this for clinical practice is that it is always necessary to obtain a good account of the child’s developmental history.
5 A better understanding of the processes  underlying a child’s 
development will lead to far better interventions and prevention.

235
Once we have a better understanding of the distal  and proximal
causes of behaviour, better targeted interventions will follow.
Developmental theories and views
There is a bewildering set of mini-models and mini-theories of developmental processes, each trying to deal with changes in children’s functioning either at different periods in their lives or in different psychological functions such as perception, language, and memory. By and large, the different theories seem to ignore each other’s work—and many also seem keener on theories than on data that might test the theories.
For example, Piaget’s theories predominantly address how chil-
dren develop a cognitive understanding of their world. His was a biological view of development, and his cross-sectional methodol-ogy emphasized the separation between the stages he posited. Staats
(5) argued that most of the phenomena described by Piaget

(5) argued that most of the phenomena described by Piaget 
and his followers could be interpreted within a social learning theory framework that instead emphasized the continuity of devel-opment across stages.
Kohlberg’s theory of moral judgement is a stage theory that 
differs radically from Piaget’s in that the different forms of reason-ing said to typify different stages can coexist. However, the way in which children (or adults for that matter) judge an ethical dilemma does not necessarily determine how they behave. Most ﬁ  nanciers 
would have little difﬁ  culty in providing sophisticated moral judge-
ments on Kohlberg type tasks, but many ﬁ  nanciers also present the 
unacceptable face of capitalism in their ruthless dealings. It is not the case that the older we are, the wiser we behave.
In Freud’s theory of psychosexual development, children are seen 
as passively passing through stages, their development being

as passively passing through stages, their development being 
impeded by obstacles or even regressing in the face of trauma. This 
view owes more to literature than to science, and the evidence on children’s psychosexual development clearly shows that whatever Freud was unaware of during the latency period, children are cer-tainly far from inactive.
(6)
Apart from being stage theories, these three sets of inﬂ  uential

(6)
Apart from being stage theories, these three sets of inﬂ  uential 
theories really have very little in common. The psychological mech-anisms determining growth of cognitive understanding bear little relationship to any that supposedly underlie socio-emotional behaviour. None of the theories take into account all of the work done in perceptual development, language development, develop-ment of memory, development of peer relationships, development during adolescence, and so on. They pay little attention to the work on individual differences in personality or temperament, or to bio-logical development generally.
A totally biological, determinist view of development was anath-
ema to the new theorists of behaviour modiﬁ  cation and behaviour 
therapy in the 1960s. It was seen as too pessimistic, offering little hope of change. By ignoring the biological basis of behaviour and 
seeking explanations solely in the here-and-now (proximal) inﬂ  u-

ences on behaviour, they undoubtedly broke through to a much more optimistic era of interventions.
Simultaneously, child developmentalists were recognizing the 
contributions the child brought to all aspects of development. The child has increasingly been seen as an active participant in develop-ment. The direction of inﬂ  uence was not all one way: the child 
helped shape the environment. Thus, parents react to individual differences in children. Different children call out different responses from their social environment. As parents have known all along, 
children do have different temperaments from birth, and these shape how they develop.
(7,8)
The implications of this for child psychiatry are many. For 
example, it implies that clinicians must take into account a child’s temperament when planning treatment.
(7,9) Children who are

(7,8)
(7,9) Children who are 
extremely introvert react differently to praise and punishment than children who are extremely extrovert.
(9,10) They also respond 
to different teaching styles in the classroom. Such differences need to be accommodated in setting up individualized treatment programmes.
With young infants, it can be very reassuring to a parent to be 
told that anyone would ﬁ  nd their unpredictable child difﬁ  cult to 
rear. It can boost parental self-conﬁ  dence to be told (when true) 
that their parenting style is perfectly adequate for most children—just not effective with this particular one. This reassurance should greatly alter the way such a parent participates in parent training programmes that are increasingly part of primary and secondary level child mental health services.
(11)

(11)
All this is not to say that stage theories carry no implications 
for child mental health services. Far from it. It is very helpful to remember that young children think and reason about their worlds differently from older children. This has to be borne in mind when interviewing children, when trying to elicit their own understanding of their problem, and, equally, when giving them instructions, feedback, or explanations. However, it must again be emphasized that the stages should only ever be regarded as rough guidelines. We know that there are such wide individual differ-ences in the rate at which children develop that we should never make assumptions about the individual child knowing only his chronological age.
Let us take one example that increasingly confronts clinicians—
the issue of helping children deal with bereavement. It is not until around the age of 10 or 11 that most  children appreciate that 
death is both universal and irreversible.
(11–14) This helps explain

(11–14) This helps explain 
why some younger children show an almost casual, matter-of-fact interest in death of a loved one and are less upset by it than adults are.
(13) But it would be wrong to assume that all younger children 
fail to have an adult appreciation of the signiﬁ  cance of death, 
and indeed some children as young as 4 years old have been found to have a mature understanding. Knowledge of the broad outline of the development of the conceptualization of death helps clinicians formulate their questions, but the onus must always be on the clinician to check whether or not the individual child con-forms to the average. The adult’s task may not be ﬁ  nished when 
they have helped a young child to understand bereavement at the level the child can cope with. That same child will probably want to revisit the issue when she is older and can understand it in a more mature way.
(15) What is true of bereavement also holds true for

(15) What is true of bereavement also holds true for 
understanding any other major life event and its effects on the child.
Critical issues in development
When one takes a closer look at how children develop, one cannot help but be amazed at the complexities of the process. Children the world over start using words around their ﬁ  rst birthday and within 
a couple of years more, they are talking in complex sentences using complicated ideas. The contrast between the language development of most children and the minority who suffer a severe mental 2.5.1 developmental psychology through infancy, childhood, and adolescence

SECTION 2  the scientific basis of psychiatric aetiology 236
handicap is devastating. Likewise, blind children start to smile at 
the same time as sighted children; deaf children start to use a similar range of phonemes; children in Japan, France, and Britain all start uttering the same range of sounds only to have them nar-rowed down to those they need in their native language—with the later consequence that they may not even be able to discriminate some of the unused sounds, let alone incorporate them when learn-ing a foreign language. The broad developmental trajectory seems very similar across cultural groups, but particular children do not always follow the average in a smooth, predictable way.
Rutter and Rutter
(16) draw attention to a number of issues that

(16) draw attention to a number of issues that 
need to be considered when trying to understand developmental processes. Clinicians are understandably focused on trying to make sense of cases where something has gone wrong in development. Mostly in child psychiatry, abnormal behaviours of children are quantitatively different from normal rather than being qualitatively different. Disorders following brain damage or genetic/chromosomalabnormalities and many involving very severe degrees of mental handicap, including infantile autism, are increasingly recognized as being qualitatively different. Most of the other disorders seen in child and adolescent mental health services are probably best viewed as deviations lying at the extreme of a continuum. But why do some children break down under stress while others do not? Why are some more resilient than others? What factors protect 
children against environmental and social stressors? Is it really the

children against environmental and social stressors? Is it really the 
case that severe depression in late adolescence is just the extreme end of a continuum ranging from happiness through sadness to suicidality? In order to tackle these issues, it is necessary to clarify some of the concepts of development.
1 One should not assume that the same mechanisms underlie 
both normal and abnormal development.
2 A biological perspective is necessary to understand human 
development fully. The brain is clearly the most important organ concerned—the genetic inheritance, insults during criti-cal periods of brain growth, hormonal changes—all these have considerable inﬂ  uence on how children develop.
3 One has to expect both continuities  and discontinuities  in devel-
opment. At times, continuities are intrinsic to the particular process as in language development; at other times, continuit ies—
as in academic attainment—are in large part inﬂ  uenced by con-

tinuities imposed by the social environment. Parents concerned about education inﬂ  uence the choice of schools and provide 
support for learning.
4 The timing  of an experience is as important as its nature. The 
brain is most vulnerable to insult when it is developing most rapidly, at and shortly after birth. Severe disruptions in caretak-ing have their greatest effects from around 9 months to 2 or 3 years. Before then, the infant does not show the same quality of selec-
tive attachments; after language is well established, the child can 
better hold the memory of a loved one, and that may act as a protection against the separation.
5 Children are active  creatures. Not only do they call out responses

5 Children are active  creatures. Not only do they call out responses 
from others, but as they develop cognitively and linguistically, they actively seek to make sense of their world. They appraise threat from others, even if they do not always get it right. When 
they are involved in a major catastrophe, their assumptive 
world
(17) can be literally turned upside down and they take a long time to reconstruct the world as a safe place. The way the 
child interprets experience will come to determine in part how similar experiences are responded to in the future.
6 ‘Continuity may be heterotypic as well as homotypic’
(16) (p. 8). 
The brilliant idea developed in the New Y ork Longitudinal Study
(18) of temperament was that rather than seeking evidence

(18) of temperament was that rather than seeking evidence 
for predictability and continuity in particular infant behaviours across times when behaviour was developing rapidly, the inves-tigators looked instead at how a variety of topographically different behaviours were expressed and found considerable continuities in such aspects as regularity of functions, strength of response, and predominant reaction to new stimuli. Thus, they adduced evidence of temperamental characteristics that were independent of the speciﬁ  c behaviours shown, and moreo-
ver, these temperamental characteristics proved to be predictive of later behaviour and adjustment.
(16)
7 Both risk and protective factors, and the interactions between

(16)
7 Both risk and protective factors, and the interactions between 
them, must be considered. Not all apparently adverse experiences are necessarily wholly bad for healthy development. In the same way that exposure to a virus or infection can boost resistance to infection, so exposure to mild stressors may boost resistance to other stressful experiences later. In part, this is the basis for stress inoculation therapy.
(19) Some would argue that young 
children should have practice in separating from parents under enjoyable conditions so that in the event of a sudden, unexpected, or traumatic separation being necessary, the effects of experience will be mitigated.
8 As noted earlier, continuities may arise indirectly in that the way

8 As noted earlier, continuities may arise indirectly in that the way 
parents or society in general support attainment and in turn entry to the job market. The moderately high correlations between early attainment and later earning power are thereby in part determined and supported environmentally.
9 Similarly, the achievement of a particular behaviour may set in 
motion a chain of events. It is important to understand the processes underlying such a sequence. T oo often studies are short-term and cross-sectional in nature and despite being aware of the pitfall of confusing correlation with causality, investigators remain prone to identifying a correlate as being a causal agent. For example, in the early days of studies of reading difﬁ culties, it was noted that poor readers did badly on tests of 
visual perception. It was assumed that they therefore had a visual-perceptual deﬁ  cit and generations of poor readers were subjected

visual perception. It was assumed that they therefore had a visual-perceptual deﬁ  cit and generations of poor readers were subjected 
to hours of mindless tracing of lines and walking along benches. The end result was that they performed better on the particular visual-perceptual test but they were no better at reading! A dif-ferent experimental design was needed to demonstrate causal relationships between psychological processes and poor read-ing,
(20) and when that was understood, the way was open for 
better remedial work based on a proper understanding of causal mechanisms.
This can also be viewed as an error in confusing a risk indicator
with a risk process . Forty years ago, studies of the dehumanizing 
effects of institutionalization on adults and children
(21) found that 
poor living conditions and block treatment of residents were relat-
ed to a greater risk of behavioural and emotional problems. In one 
set of studies, a good indicator  of block treatment was whether

set of studies, a good indicator  of block treatment was whether 
patients had their own toothbrushes. Clearly, providing individual

237
toothbrushes to all would not make much difference if all the other 
aspects of institutionalization remained in force. A fuller under-standing of the process  of institutionalization is needed in order to 
be able to develop more humane care that improves development.
These critical issues demonstrate just how complicated the rela-
tionship between nature, experience, and development can be. But human beings are indeed very complicated, thank goodness, and so a proper appreciation of all these factors is needed in order to be able to understand how a particular child reached a particular point in development; to be able to predict what the future may hold for a child and to be able to develop rational interventions that have a hope of making a real difference to children’s lives.
Developmental psychopathology
Developmental psychopathology emerged in the 1980s to bridge the rift between academic and clinical child psychology.
(22, 23) ‘The

(22, 23) ‘The 
developmental psychopathologist is concerned with the time course of a given disorder, its varying manifestations with develop-ment, its precursors and sequelae, and its relation to non-disordered patterns of behaviour’ (p. 18).
(23) Developmental psychopatholo-
gists, like social learning theorists, look to normal development to illuminate pathological development. They are interested in conti-nuities and changes in behaviour across time. This ﬁ  ts in well with 
the tradition of risk research
(24) and attempts to answer questions 
not only about why some children are more vulnerable than others, but also about what protective factors operate to lessen the impact of stressors.
Sroufe and Rutter,
(23) following Santostefano,(25) articulated sev-

eral propositions that are broadly agreed across the many different theories alluded to above:
(a) Holism
‘The meaning of behaviour can only be determined within the total psychological context’ (p. 20).
(23) Thus, behaviour such as crying 
can only be evaluated according to the age of the child and the cir-cumstances in which it occurs. Crying on separation would be seen as usual for a 3-year-old, but unusual in a 15-year-old. One cannot simply judge the signiﬁ  cance of a behaviour simply on the basis of 
its physical, stimulus properties, but one has to evaluate it within the broader social context.
(b) Directedness
Children are not passive reactors to the demands of the environment. Development consists of a reorganization of previous elements, skills, and behaviour, not just a linear addition of skills.
(c) Differentiation of modes and goals

Over time, children’s reactions to their environment become both more ﬂ  exible and increasingly complex in organization. Thus, one 
sign of pathology is for children to get stuck in a particular way of trying to solve a problem.
(d) Mobility of behavioural functions
Earlier behaviour becomes integrated into later patterns, and ‘the individual does not operate only in terms of behaviours that deﬁ  ne 
a single stage. Especially in periods of stress, early modes of func-tioning may become manifest’ (p. 21).
(23) In other words, under 
stress, those patterns of behaviour that have most recently become integrated into the child’s repertoire are most susceptible of disruption. This is very different from the unsatisfactory concept of regression in which all skills achieved remain available in the child’s 
repertoire; some earlier ones also manifest at times of stress.
(e) The problem of continuity and change

Above all, development is seen as lawful, even though we are still far from understanding the processes involved in these laws. Sroufe and Rutter
(23) emphasize: ‘the continuity lies not in isomorphic 
behaviours over time but in lawful relations to later behaviour, however complex the links’ (p. 21). As noted, Thomas, Chess, and Birch
(18) were among the ﬁ  rst to demonstrate continuities in the 
style  of behaviour (temperament) rather than continuities of 
behaviour per se .
It is now recognized that there are many complex ways in which 
child behaviour is related to later and even adult adjustment.(26)

One of the most powerful predictors of later adult psychopathology is inadequate peer relations. The mechanism by which these work may be due to two interacting processes: (1) Poor peer relations are signs of failure to adapt during childhood, and that failure persists; (2) social support later acts as a buffer against adult stressors.
(23)
Clearly, this view of development, with its implications for

(23)
Clearly, this view of development, with its implications for 
psychopathology, is far removed from the lessons learned from the Skinner box. Y et what has been learned from the paradigms of classical and operant conditioning must also be integrated into ways that child therapists assess children’s problems if we are to provide better treatments. This holistic view manages to incorpo-rate ideas on the biological basis for behaviour and the notion of the child as an active participant interacting with his or her effective social environment within a broad social learning frame-work.
(27,28)  Understanding how a problem has arisen may provide 
useful guidance on what aspects to focus on, but the treatment will still focus on the present. There will be implications for main-taining treatment gains and preventing future problems, as well as implications for preventing such problems arising in other children.
For clinicians more used to working with adult patients, it is

For clinicians more used to working with adult patients, it is 
worth pointing out that children differ in many ways from their grown up counterparts. This has implications for improving diag-nostic classiﬁ  catory systems in that both DSM and ICD are still too 
adult oriented and pay insufﬁ  cient attention to developmental 
aspects of disorders.
(29–31)
Garber(32) makes the point that children differ from adults in 
cognition, language, physiology, and emotions. Such maturational differences may impact children’s abilities to experience or express certain affects, cognitions, or behaviours, and thus the manner in which symptoms are expressed may differ over the course of devel-opment (p. 32). Recent work on the effects of major disasters and acute stress on children’s adjustment, it became evident that children as young as 8 years old showed most of the symptoms of post-traumatic stress disorder ( PTSD )—with unpleasant thoughts,

poor concentration, and sleep disorders predominating.
(33,34)
Parents and teachers were often unaware of the nature and extent of the children’s subjective distress, and only sympathetic but direct questioning elicited the full spectrum of symptomatology.
The criteria for PTSD are less appropriate for children under 
8 years of age. Pre-school children often react with more repetitive play and drawing than older ones. Even the youngest children will report very disturbing, intrusive thoughts about the disaster. Scheeringa et al.
(35) suggest varying crit eria for making the diagnosis2.5.1 developmental psychology through infancy, childhood, and adolescence

SECTION 2  the scientific basis of psychiatric aetiology 238
of PTSD in young children. Leaving aside the logical problem of alter-
ing criteria but keeping the same name for the supposed underlying condition, this clearly is one aspect of the isomorphism mentioned earlier. It is also interesting to speculate whether the repetitive play seen in 6-year-olds is functionally equivalent to the intrusive thoughts seen in 10 year olds, and when the one changes into the other.
Garber also notes that some disorders, such as mental handicap 
and autism, ﬁ  rst manifest in childhood and persist into adulthood.

and autism, ﬁ  rst manifest in childhood and persist into adulthood. 
Others, such as encopresis and enuresis manifest in childhood, but rarely persist into adulthood unless part of a more global develop-mental delay. Some, such as anorexia and bulimia, are more typical of adolescence. Suicide, although rare before puberty, is rapidly becoming the major cause of death in adolescence, but peaks in old age. Major depression and schizophrenia are rare in childhood, although precursors are being more ﬁ  rmly established. While the 
wish to treat disorders in childhood so as to prevent them continu-ing to adulthood is laudable, treating them to improve adjustment during childhood is equally valid.
Linking developmental psychopathology to 
developing children
These exciting ideas need to be brought out of experimental settings

These exciting ideas need to be brought out of experimental settings 
and into clinics—the aim of developmental psychopathology theorists. In the second half of this chapter, some of the key aspects of child development relevant to clinical practice will be highlighted in this framework.
(a) Individual differences
Children differ in their personality, character, or temperament. European psychologists have always emphasized these individual differences and adduced evidence that many were based on bio-logically determined ways of responding to the world. While the three factor structure of personality developed by Eysenck evolved into the big ﬁ  ve structure of today, an issue remained as to how one 
could demonstrate continuity  in personality from a very early age.

could demonstrate continuity  in personality from a very early age. 
The same issue bedevilled studies seeking to establish continuity in differences in intellectual functioning—simply put, little babies show such a different repertoire of behaviour from mobile, talking pre-school children that it was impossible to test the same behaviours at different ages.
In part, the problem was solved in the New Y ork Longitudinal 
Study
(18) (see Box 2.5.1.1 One) by looking at differences in style of 
behaviour rather than differences in content or topography. By avoiding talking of biologically based personality, the ﬁ  ndings 
reawakened interest in the genetics of individual differences.
In the original sample of 78 babies, the investigators were able to 
demonstrate considerable individual differences in temperament. 
There was good inter-rater reliability in making these judgements

There was good inter-rater reliability in making these judgements 
and direct observations agreed well with reports from parents. The temperamental characteristics were found to be stable over both the short (2 years) and medium term and even predicted reasonably well into late childhood.
Three broad types of temperament were characterized—children 
who were regular, predictable, and showed generally positive reactions—the easy babies; those who were almost the opposite—whom Chess called the mother killers and a sizeable minority who were slow to warm up to new situations but who adjusted eventually. The difﬁ  cult children were over represented in those 
who developed behavioural problems in later childhood.(b) Cognitive development

One of the major aspects of development that exercises parents and teachers alike is how best to improve the intellectual functioning of children, be that in language, reading, memory, or general intelligence. T o what extent individual differences in these areas are predominantly related to heredity or to environment continues to be a popular, if sterile, source of argument. Clearly, the end result comes from an interaction between genetic predisposition and experience, but there remain issues of how best to manipulate the environment so as to help children gain their maximum potential. T o that end, an understanding of modern behavioural genetics is essential. Here, some of the methodological issues in assessing babies’ cognitive processes and ﬁ  ndings in cognitive development, 
language, and memory are considered.
(c) Getting inside the baby’s head

Until a baby starts to speak, it is difﬁ  cult to know what they are think-
ing. Fond parents interpret wind-driven grimaces as smiling; every child is seen as recognizing people and being smart from a young age. But how can one tell what really goes on inside a baby’s head?Box 2.5.1.1 Temperamental characteristics
The repertoire of infant behaviour is so different from that of 
the pre-school child that it proved very difﬁ  cult to examine 
whether there were any continuities of behaviour across the ages. Thomas et al.
(18) and their collaborators in the New Y ork 
Longitudinal Study were among the earliest to show continuities across the age, but continuities in style  of behaviour rather 
than content . Through a mixture of observation and exhaustive 
interviews with mothers, they originally developed nine differ-ent categories of behavioural style or temperament .
Mainly

Mainly
1. Active 1. Passive2. Regular: (e.g. in feeding  2. Irregular
 and sleeping habits)
3. Reacts intensely  3. Reacts mildly
 (strongly)
4. Shows approach behaviour  4. Shows withdrawal 
 to new people, places,    behaviour toys, foods, etc.
5. Adaptive—adapts fairly  5. Non-adaptive
 easily to change
6. Reacts easily to  6. Reactions slow
 small changes
7. Predominantly good  7. Predominantly bad
 moods—happy,    disposition—fretful, contented disposition   hard to please
8. Persistent in what  8. Non-persistent
 she/he is doing as regards  time, and in the  face of difﬁ  culties
9. Easily distracted from 9. Not easily distracted
 whatever she/he is doing

239
Robert Fantz(36) studied infants’ eye movements and used ﬁ  xation 
time as a measure of preference for different stimuli. Film record-ings were made of light reﬂ  ected off the baby’s eyes. In a study of 
30 infants tested weekly from 1 to 15 weeks of age, it was shown that the infants spent longer looking at complex than simple patterns. This demonstration of a clear perceptual preference in the ﬁ rst few weeks after birth gave the lie to the view that all begins as 
a big, booming confusion. Infants as young as one week show clear preference for human faces over other shapes presented to them some 10 in. away.
Fantz took advantage of the technology of the day. Since then, 
others have utilized measures of changes in temperature, in galvanic skin response and in heartbeat to provide behavioural indices of preferences. In addition, investigators have used various indices from learning and conditioning paradigms.
Results from such studies highlight the extent to which infants

Results from such studies highlight the extent to which infants 
enter the world ready for social interaction. Infants are highly dependent on their parents because of the cortical developments and increase in brain volume required to allow the special human cognitive characteristics to develop that take place after  the baby 
has made its way down the birth canal. Infant’s readiness to be part of a social interaction, imbued with intentionality, appears to serve a survival function.
The neonate has remarkable hard-wired skills that can be detect-
ed from within moments of birth, while the neonate is in a period of alert inactivity. However, there are limits to the extent of the early ability. Eyesight acuity is about 1/30th of adults at birth and 
develops over the next 4 years, although signiﬁ  cant improvements

develops over the next 4 years, although signiﬁ  cant improvements 
arise by the second month. Despite problems with visual acuity and focusing, even neonates can track objects, albeit jerkily, and scan for simple, visual features, such as linearity, luminance, and symmetry when stimuli are within about 10 in. of their face.
(37)
These intrinsic visual abilities combine with preferences for certain spatial forms found in the human face, e.g. a preference for vertical over horizontal symmetry. Fagan
(38) tested visual preference in 
7-month-old babies and later measured their intelligence when they were 3 and 5 years old. The time spent looking at the novel stimulus when a baby correlated 0.42 with performance on the later Picture Vocabulary T est. Thus, it is getting easier to measure various indices of baby’s reactions and some of these are found to be usefully predictive of later development and adjustment.
Hearing is pretty much complete by the 5th or 6th week of foetal

Hearing is pretty much complete by the 5th or 6th week of foetal 
life, with sophisticated auditory discrimination abilities along the dimensions of pitch, volume, tone, and duration. Hence neonates may come into the world already familiar with soap opera theme tunes, but so too are they familiar with their mother’s voice and are able to orientate towards them from the start. Neonates have a preference for women’s voices over men’s and unlike the speciﬁ  city 
shown towards the mother, appear to show little preference for 
their father’s voice compared with other men.
(39)
Bathed in amniotic ﬂ  uid in the womb, it is unclear whether the 
foetus has strictly speaking smelled  the mother before birth, although 
their olfactory system is well-developed in utero . Nonetheless, within 
hours of birth neonates demonstrate a preference for their mother’s smell and, within days, can reliably orient their head towards breast pads worn by their mothers over those worn by other women.
(40)

(40)
Meltzoff and colleagues have demonstrated that a neonate’s 
social sensitivity is not just a passive turning to stimuli, they can also actively imitate them.
(41) Indeed, within moments of birth, neonates are able to mirror adult’s facial expressions such as tongue 
protrusions or mouth openings. Quite how this process operates at a cognitive level is unclear. One can speculate on its function as a way to provide a satisfying contingency for a parent that helps imbue the infant with a sense of communication, agency, and personhood. Overall, neonate’s abilities to discriminate between stimuli and their hard-wired preferences for some constellations over others lead them to orient towards their caregivers, as the very beginnings of a selective attachment.
(d) Piaget and cognitive development
Piaget was a biologist who studied amoebas for his doctoral work. Biological models found useful for that purpose clearly inﬂ  uenced

Piaget was a biologist who studied amoebas for his doctoral work. Biological models found useful for that purpose clearly inﬂ  uenced 
the way he regarded cognitive development. He held to a sort of moving homeostasis—children develop a model of the world. New information that challenges that model is gradually assimilated and eventually the model accommodates the new ways of thinking—a bit like an amoeba reaching out to a piece of food, surrounding it and assimilating it.
According to this theory, the child passes through three broad 
stages of thinking (see Box 2.5.1.2): A sensori-motor stage, a long stage where they think in terms of what he called concrete opera-tions, and ﬁ  nally a stage where they can think logically.
Piaget’s stage theory has been very inﬂ  uential and helpfully

Piaget’s stage theory has been very inﬂ  uential and helpfully 
sparked off a great deal of research which has led to a much better understanding of how children develop cognitively. However, his original models were somewhat simplistic and to have seen only three major stages covering a period of such rapid development 
Box 2.5.1.2 Piaget’s stages of cognitive development
Birth to 18 months: sensori-motor stage
Cognition is based mainly on the child’s actions and six 
sub-stages were described. A key concept at this stage is that of object permanence—the ability to understand that an object continues to exist even when it is out of sight. Infants of 12 months will continue to look for an object where an experimenter hides it, even when they watch the experimenter move it. It is as if the object belongs only in a particular place.
18 months to 12 years: concrete operations
This is the stage of concrete oper ations. At the early stag e, language

develops rapidly. Children begin to demonstrate symbolic play, showing that they have memories and internal representations. Many ingenious little experiments were developed to illustrate how children’s thinking about their world develops. Various other conservation tasks—of length, mass, and number for instance—convince teachers that children think differently about the world than adults and this has had a major—if not always beneﬁ  cial—effect on ways of teaching.
12 years and over: formal operations
From around puberty onwards, the child is able to formulate and 
test hypotheses about the world. The child realizes that mass and volume can be altered in many ways, but they remain essentially unchanged. Children can examine their own thought processes and can begin to reason more logically.2.5.1 developmental psychology through infancy, childhood, and adolescence

SECTION 2  the scientific basis of psychiatric aetiology 240
strikes one as inadequate. Moreover, for the clinician, the question 
one often wants to raise is how can one use this understanding to bolster the reasoning of a child who is developmentally delayed—what Piaget witheringly dismissed as the American question. Piaget tended to argue that children could not be hurried through the stages. However, critics soon argued that some of the regularities that were apparently replicated in his work owed more to the manner in which the tasks were presented to the child than to any necessary underlying cohesion in types of thinking.
A typical experiment is to give a child two pieces of clay that are

A typical experiment is to give a child two pieces of clay that are 
identical. Then one is rolled out into a sausage and the child is asked if they remain the same. Alternatively, the child is shown two test tubes of differing diameters. The same amount of liquid is poured into each, but, of course, reaches different heights. Which test tube has more liquid? Not surprisingly, younger children make more errors than older ones and it has been shown that conserva-tion of mass (seeing that the quantity of material remains the same in spite of changes in shape) is acquired around 7 to 8 years, while conservation of weight  is not achieved until 9 or 10 years. It is not 
until 11 or 12 that the child typically thinks that each shape also occupies the same amount of space (i.e. achieves conservation of volume ).
Bruner was one of the earliest to demonstrate that children’s

Bruner was one of the earliest to demonstrate that children’s 
judgements could be radically manipulated by small changes in the ways the tasks were presented. For example, in the studies on conservation of volume, a screen was placed between the child and the test tubes so that only the tops showed but not the levels reached by the liquid. This simple change meant that many younger chil-dren now understood that by pouring liquid from one container to another—perhaps something done daily in the bath—nothing had changed. Some children as young as 4 years were able to perform the revised task, but once they had to make the judgement again without the screen, they reverted to the more primitive form of reasoning. In other words, young children are more at the mercy of their perceptual impressions, a ﬁ  nding that needs to be taken on 
board in many circumstances.
(e) Language development

Children communicate from the beginning. They signal their basic needs, often by crying. Parents soon learn to respond to the differ-ing signals. Their own child’s crying can be very aversive to most parents and so they quickly learn how to switch the noise off! Autistic and brain damaged children produce grossly abnormal cries, but often parents with little experience do not recognize the unusual nature of the cry. Whilst lower primates and other animals can communicate, none use language in the ﬂ  exible way that 
human infants come to do. Language—both spoken and written—is truly the most human of attributes.
Sophisticated social interaction is a precursor to the development 
of language. Though the infant is hard-wired for social interaction, it is not clear that these behaviours are strictly communicative in the sense of being intentional acts. What appears to be an early

communicative competence may be best understood in terms of a 
social releaser  model, where caregivers’ interactions are triggers 
that release hard-wired reﬂ  exes from the infant, little different from 
the familiar palmar grasp reﬂ  ex of the ﬁ  rst month that causes an 
infant to grip an adult’s thumb, even in their sleep. In this formula-tion there is no sense of a two-way communicative interaction being shared between carer and infant.From approximately 2 months of age, infants appear to be active 
participants in the interactions that caregivers and their babies 
regularly play. When carers adjust their speech to the infant’s pref-erences for high-pitched, rhythmic, and repetitive speech, often referred to as motherese  and hold their face about 12 in. away, with-

in the infants optimal focal range, a dynamic dance of turn-taking between carer and infant can be observed. The infant’s attention is held, shared smiling can occur, the pitch and tone of utterances becomes matched and the infant can be observed to make distinctive formations with their lips referred to as ‘pre-speech’ . Caregiver and infant certainly appear to be experiencing social reciprocity. Some clever experiments based on perturbing the reciprocal nature of the infant caregiver interaction have challenged the notion of a social releaser model and given support to the infant’s sophisticated early developing sensitivity to social reciprocity.
The still face paradigm requires the infant’s partner to disturb 
the relationship by substituting their dynamic interaction by hold-ing a still, expressionless face.
(42) Presented with this perturbation,

(42) Presented with this perturbation, 
infants will initially increase their gesturing, as if to draw the adult back in, but become increasingly distressed, crying, or grimacing as this unnatural state continues. Of course, this is a relatively gross perturbation and technological advances have allowed develop-mentalists to alter more subtle aspects of the real-time contingency between an infant and its mother using a video link. Murray and colleagues ﬁ  lmed mothers and infants interacting over a video link 
and then altered the contingency by replaying a segment of the mother’s interaction to the infant.
(43) Infants as young as 8 weeks

(43) Infants as young as 8 weeks 
were able to detect this perturbation, and initially showed reduced levels of engagement followed by distress and protest. The levels of engagement rose again when the link was switched back to a live interaction. The replay condition demonstrated that simply pre-senting caregiver behaviours that had been previously adequate to elicit sustained interaction were no longer appropriate when they were taken out of the context of the dynamic ﬂ  ow between infant 
and caregiver. Thus it was not simply the presentation of maternal signals that triggered the release of infant communicative behav-iours, but like a dance or a conversation, it was the to and fro sequence of behaviours between infant and caregiver that set the context of the ﬂ  ow of behaviours.
Language has not been the subject of serious study until the past

Language has not been the subject of serious study until the past 
50 years. Beginning with simple descriptive studies of the acquisi-
tion of words, the complexities of grammar and cross-cultural comparisons, studies of language development now encompass many other dimensions from neuropsychological, brain imaging, and genetics. What stands out is just how difﬁ  cult it is to affect the 
onset of language by manipulating the environment. It takes extraordinarily environmental deprivation to interfere with language development and even then, when the environment is normalized, considerable catch up occurs.
The grunts and single syllables of the ﬁ  rst couple of months 
soon give way to the production of the full range of phonemes and babbling between 2 and 4 months. States of feelings are communi-cated clearly by 3 to 7 months. From 6 months, the baby begins to 
imitate simple sounds and unreinforced phonemes disappear from

imitate simple sounds and unreinforced phonemes disappear from 
the vocabulary. By 8 months, the baby begins to utter two syllable combinations such as ma-ma and da-da—amongst the easiest to produce physically and, perhaps not coincidentally, the most emo-tionally evocative words parents want to hear. At around 12 months, the ﬁ  rst true word appears, usually as the infant takes his ﬁ  rst

241
step—girls reaching the milestone slightly ahead of boys. Vocabulary 
grows astronomically from one to three years and beyond. Children’s sentences get longer and more complex. A good working 
approximation is that the average length of sentences is in keeping with the number of years of age.
(46)
Studies in the 1960s and 1970s established that language

(46)
Studies in the 1960s and 1970s established that language 
development followed complicated underlying rules. The idea that children learned language by successive approximations to adult speech being differentially reinforced was quickly laid to rest. Such techniques have an important place in remedial intervention for children with deviant language development, but for ordinary children the sheer inevitability, speed, and beauty of acquisition is overwhelming. This led many to postulate that there is a genetically encoded Language Acquisition Device that guides communication, although not the particular form of language that a particular child will develop. That still depends on what language they are exposed to.
Early sentences are telegraphic with some words acting as pivots 
on which other words hang to form ﬂ  exible sentences. Thus, the

on which other words hang to form ﬂ  exible sentences. Thus, the 
pivot, ‘all-gone’ can have ‘sock’ , ‘milk’ , or ‘daddy’ added to create a 
whole range of meaningful simple sentences. Children develop 
rules for expression. A common error is for them to extract a rule and then overgeneralize it to a situation that is an exception in their particular language. For example, the present tense is used before the past tense. Instead of saying ‘I went’ children often form past participles by adding -ed to a stem and come up with the often heard ‘I goed’ . This shows they are learning a rule, even though they make some mistakes on the way.
Different ways of describing and classifying language disorders 
have been proposed in the past few years.
(44) Bishop’s(45) twin study 
ﬁ nds that when language disorder is deﬁ  ned as a discrepancy

ﬁ nds that when language disorder is deﬁ  ned as a discrepancy 
between non-verbal IQ and language score the heritability is far less than when language delay and disorder are considered without 
reference to IQ. This is important for clinicians in identifying chil-dren with such difﬁ  culties .
(f) Memory
One of the most intriguing observations in the current child devel-
opment literature is the contrast between the ever increasing evidence of just how complicated children’s cognitive development is and the phenomenon known as infantile amnesia. Basically, people have very few memories before the age of 3 years. Clearly from all that has been described earlier about the differential reactions of babies to speciﬁ  c stimuli, to their recognizing their mother’s voice or holding out their arms to their father rather than to a stranger,

children increasingly have some form of central representations that they can work on. Y et, these early memories are not accessible in later life. It is really not until language is well established that people have what is ordinarily termed memory for past events.
Clearly, infantile amnesia poses a major challenge to any theory 
of child development or personality that tries to link very early experiences with later adjustment. Y et, early experience does affect the way in which relationships are formed, so what are the mechanisms? As the different types of memory (See Box 2.5.1.4) are better understood, so better assessment of these functions is possible.
Some very recent work has looked at implicit and explicit mem-
ory as well as attentional processes in children with generalized anxiety disorder, PTSD and depression. Broadly speaking, the pre-liminary ﬁ  ndings are in accord with the voluminous ﬁ  ndings with

ory as well as attentional processes in children with generalized anxiety disorder, PTSD and depression. Broadly speaking, the pre-liminary ﬁ  ndings are in accord with the voluminous ﬁ  ndings with 
adult patients, namely that depressed children tend to have biases in memory for sad things, while anxious children do not. In con-trast, children with anxiety disorders (including PTSD) have biases in attention that make them attend more to threatening cues in their environment—or at least to threatening words projected on computer screens. Studies using these adult-generated paradigms but utilized within a developmental framework should greatly increase our understanding of why some children break down under stress and others do not. Biases in cognitive processing of 
Box 2.5.1.4 Memory
Goswami(48) summarizes many ingenious experiments that

Goswami(48) summarizes many ingenious experiments that 
establish the parameters of children’s memory. While parents and teachers often talk about children having problems with memory and even short-term memory, developmental psychol-ogists have worked on much more complex paradigms and identiﬁ  ed a number of different memory systems:
Recognition memory  is simply the ability to realize that a par-
ticular stimulus has been encountered before. Recognition is always easier than recall—as those learning a foreign language can testify. Once established in the ﬁ  rst year of life, recognition 
memory does not change much.
Implicit memory  is another term for memory without aware-
ness. Although not able to put it into words, people can act 
differently to previously exposed stimuli than to novel ones. This seems to be fully developed by around 4 years of age.
Episodic memory  involves awareness. It is this memory system

Episodic memory  involves awareness. It is this memory system 
that organizes memories into stories or scripts concerning 
similar activities. These scripts contain both temporal and causal 
information. The ability to learn sequences in a particular chain of events does develop with age. It is now that one realizes that there needs to be some mechanism to get rid of many of the memories for everyday activities, otherwise the whole memory will get clogged up with non-essential information. In other words, mem-ory processes are seen as being very active with some memory traces remaining in (technically) short-term memory for only a few seconds unless operated upon and stored in long-term store.
Eye witness memory  has taken on a special importance as

Eye witness memory  has taken on a special importance as 
children are expected to testify in court on things they have witnessed happening to themselves or to others. Children can Box 2.5.1.3 Language development
Vocabulary grows astronomically from 1 to 3 years and beyond. 
Children’s sentences get longer and more complex. A good work-ing approximation is that the average length of sentences is in keeping with the number of years of age:
Average length of sentences—2–5 years
Age in months 24 30 36 42 48 54 60
Average number of 
words per sentence1.7 2.4 3.3 4.0 4.3 4.7 4.6
From Smith.(46)2.5.1 developmental psychology through infancy, childhood, and adolescence

SECTION 2  the scientific basis of psychiatric aetiology 242
emotional reactions are implicated and can now be studied more 
readily.(47)
Social and emotional development
Alongside cognitive development, children are developing both socially and emotionally. It has been recognized for years that chil-dren brought up in institutions, away from their natural parents, often develop serious and subtle problems in social interactions and emotional development.
Arising in part from his studies of infants in institutions and his

Arising in part from his studies of infants in institutions and his 
collaborative studies of children’s reactions to being in hospital, as well as his dissatisfaction with contemporary psychoanalytic theory, Bowlby turned to ethology for an understanding of early infant relationships. He came to view the intense relationship between the infant and the caretaker, usually but not always the biological mother, as serving a biological survival value and as hav-ing been produced by natural selection. Bowlby proposed an attachment system that served to keep the child safe during the 
extended dependency of human infancy, by ensuring proximity to 
speciﬁ  c and reliable caregivers.
(50)
As memory develops in the ﬁ  rst year of life, and as the infant

(50)
As memory develops in the ﬁ  rst year of life, and as the infant 
becomes more able to express emotion and to move independently, so there is evidence for selective attachment. This is shown round about 6 to 8 months onwards by the upset at leaving the attach-ment ﬁ  gure, by seeking comfort when threatened and by a general 
wariness of strangers.
The idea that attachments were simply associative learning—the 
baby comes to love the person who feeds him—was quickly dism issed
by the evidence from Harlow’s studies of infant monkeys. They attached to the cuddly terry-towelling surrogate rather than the wire surrogate where they were fed. Rather, selective attachments in the human served to protect the infant during the prolonged period of helplessness. The function of attachment changes over 
the years, with children using an attachment ﬁ  gure as a secure base

the years, with children using an attachment ﬁ  gure as a secure base 
from which to explore. Thus, almost paradoxically, the well attached toddler may move away from the attachment ﬁ  gure more than the 
insecurely attached counterpart. Attachment is not the same as clinginess.
The attachment system is just one amongst several innate systems 
proposed to operate in infancy, and it is the interplay between com-peting behavioural systems that led to the gold standard measure of attachment in infancy. Mary Ainsworth’s based her Strange Situation Procedure ( SSP) around observations of infants in 
Uganda.
(51) The SSP pits the attachment system against the fear

Uganda.
(51) The SSP pits the attachment system against the fear 
and exploration systems, in a structured, unfamiliar situation com-prised of increasing levels of stress (e.g. strange room, strange adult, and separation from the caretaker). Observations are focused pri-marily on proximity seeking and contact maintaining behaviours during reunions with the caregiver. This measure is made possible by the development of stranger fear and mobility around the age of 9 months, and loses its validity by about 18 months as the infant’s cognitive development permits different responses to separation, e.g. symbolic representation and language. After this point attach-ment assessments become less about observed behaviours and more about language and play.
(52, 53)
The SSP originally suggested three types of infant classiﬁ  cation,

(52, 53)
The SSP originally suggested three types of infant classiﬁ  cation, 
representing organized responses to the prevailing environment: Insecure Avoidant (A) infants whose behaviour implied an attempt to minimize the importance of the attachment relationship and whose impoverished play and exploration functioned as a distrac-tion from their need of comfort from the caretaker; Secure (B) infants who sought sufﬁ  cient comfort from the caretaker to be able 
to quickly return to play and exploration; Insecure-Ambivalent, or Insecure-Resistant (C) infants whose behaviour suggested a maximization of the attachment relationship and an ambivalent recall things fairly accurately, as long as deliberate leadingquestions are not put to them.
(49) Three-year olds are more sug-

gestible than 5-year olds. Experienced adults—such as psychia-trists or judges—evaluate children’s responses to questioning about a real event using the child’s behaviour while giving their answer. Where children gave ﬁ  rm answers with lots of support-
ing details, they were judged to have clear and accurate memo-ries. Where children were uncertain and hesitant, they were seen as fabrication whereas they were hesitating because the questioner was asking the wrong questions—ones that were in conﬂ  ict with what had actually happened—they were the ones 
who were actually telling the truth. The younger, conﬁ  dent chil-
dren were often telling the adult what they wanted to hear! A great deal more needs to be done in relation to helping chil-dren recall what has happened to them without using leading questions.
Working memory  was seen by Baddeley and his co-workers as

Working memory  was seen by Baddeley and his co-workers as 
consisting of a central executive processing linked to two separate subsystems: a phonological loop and a visuospatial sketch pad. Information decays in the phonological loop in 1 or 2 s, unless it 
is actively rehearsed. It is thought that children predominantly 
use a visuospatial encoding until they switch to  the phonolog ical/
verbal system around the age of 5 years. Deaf children continue to rely on the visual encoding for much longer.
Box 2.5.1.5 Attachment
Ainsworth developed the theory and a method for detecting 
individual differences in attachment. She introduced the strange situations test in which an infant is left in the care of a stranger for a few minutes. The observer then notes how the infant copes both with the separation and with the reunion. These observa-tions led to a tripartite classiﬁ  cation of attachments:
◆Secure attachment:  The infant tends to seek proximity and

◆Secure attachment:  The infant tends to seek proximity and 
contact with the attachment ﬁ  gure, shows a preference for the 
mother over a stranger, and shows very little distress before and after separation.
◆Avoidant insecure:  The baby does not cling when held, avoids 
the mother (or caretaker) during the reunion, and does not differentiate greatly between the caretaker and a stranger.
◆Resistant insecurity:  The infant resists contact and interac-
tion with the mother. There is great distress at reunion.
◆Disorganized or avoidant insecurity:  This category had to be 
introduced when it was found that infants of severely depressed and abusive mothers showed a mixed pattern of attachments. The child shows contradictory patterns and unusual patterns of negative emotions.

243
preoccupation with the caretaker, at the expense of returning to play 
and exploration. Mary Main’s observations of children in high-risk environments, particularly those exposed to maltreatment or paren-tal psychopathology, led to an additional coding category, indepen-dent of, but complementing the tripartite Ainsworth system. Main noted a high rate of bizarre infant behaviours in the SSP of some children, which seemed to denote a lack of a clear, organized adap-tation to separation from the caregiver. There was also evidence of apprehension and fearful behaviour in the presence of the caregiver, these infants seemed disorganized/disoriented, and were catego-rized as an Insecure-Disorganized (D) attachment pattern.
(54)
A second innovation that Bowlby’s attachment theory brought 
to the study of child development was the notion that the experi-ence of the caregiving environment becomes represented as a cog-nitive heuristic or internal working model of attachment  (IWM ).

to the study of child development was the notion that the experi-ence of the caregiving environment becomes represented as a cog-nitive heuristic or internal working model of attachment  (IWM ). 
This model is a dynamic, lifelong work-in-progress , which evolves 
as environmental experience accumulates but which also guides the selection of current behaviour on the basis of past experiences. Thus the infant’s model of attachment is shaped by the experience of their caregiving environment, but simultaneously inﬂ  uences 
interactions with the infant’s environment by selecting the behav-iours most likely to achieve the goals, of say, proximity, based on what was previously successful. The IWM reﬂ  ects an adaptation to 
the current environment, but the ﬂ  exibility to adapt to changes in 
the environment is weighted by the accumulation of previous experience. So the possibility of fundamental change in attachment 
style is always possible but more difﬁ  cult the longer the old environ-

ment prevailed.
Bowlby proposed that as time goes on the IWM becomes less 
about selecting the appropriate behaviours to protect the dependent infant via maintaining proximity to a safe and reliable caretaker, but moves to a level of representation of the self in relation to others. There is evidence to support the idea that the quality of attachment in infancy has some degree of inﬂ  uence over a range of social and 
emotional outcomes in early childhood, with peers, teachers and even stretching into later adolescence and early adulthood with partners and, as parents, their own offspring.
(55) There is good 
evidence of some degree of continuity across the lifespan, but as Bowlby’s original thesis would predict, expectations of continuity should not be overstated, and the degree of continuity is particularly low in high-risk samples.
(56)
By the age of 3 to 4 years, most children show good evidence of

(56)
By the age of 3 to 4 years, most children show good evidence of 
having multiple attachment ﬁ  gures. By this age, their memories are 
so much greater that they are less dependent on the physical pres-ence of the attachment ﬁ  gure to provide security and comfort. 
Bowlby saw good attachments in infancy as laying the basis for future social and intimate relationships and there is currently an explosion of work re-examining psychiatric conditions from an attachment perspective. Thus, Bowlby saw the child as developing a cognitive model of his effective social world, in keeping with the views of other cognitive theorists such as George Kelly, Aaron Beck, and Ronnie Janoff-Bulmann.
(a)  Attachment, psychopathology, and ‘reactive 
attachment disorder’
There is sometimes confusion surrounding the ideas of the

There is sometimes confusion surrounding the ideas of the 
relationship between insecure attachment and psychopathology. An organized-insecure attachment is an appropriate response to a particular environment. At most an organized-insecure attachment might be a vulnerability factor for later problems, in the context of 
other risks, but by no means would it be a major risk factor for pathology in itself. In terms of outcomes such as behaviour prob-lems, the greatest inﬂ  uences still appear to be social risk factors, 
although attachment may confer some small additional risk.
(57)
There is stronger evidence for insecure-disorganized attachments predicting psychopathology. Aggressive behaviour problems in preschool are associated with insecure-disorganized classiﬁ  cations 
in infancy.
(58) One study has suggested some degree of homotypic

(58) One study has suggested some degree of homotypic 
continuity into late adolescence with elevated rates of dissociative phenomena echoing the bizarre stilling and freezing behaviours typical of a insecure disorganized classiﬁ  cation in infancy.
(59)
Of course, disorganized classiﬁ  cations most often occur in high-risk 
environments, so it is not always obvious if consequent psychopa-thology is a result of the attachment classiﬁ  cation or of the con-
tinuing impact of a high-risk environment. Clearer evidence for the enduring impact of disorganized attachment could be collected when the high-risk environment that has led to the disorganization is terminated.
A negative aspect of the focus on attachments has been the emer-
gence of an ill deﬁ  ned disorder described as reactive attachment

gence of an ill deﬁ  ned disorder described as reactive attachment 
disorder which seems to be diagnosable by the presence of any or all of a long list of symptoms and signs that haunted previous generations under such labels as Minimal Brain Dysfunction and the like. This has been associated in some countries with the use of assaultative holding therapies intended to break the child’s resis-
tance to forming attachments. Clearly, more careful studies need to 
be undertaken to try to pinpoint the subtle social difﬁ  culties 
presented by children whose early lives have been disrupted in fostering and adoption, but care also needs to be taken to adduce evidence for appropriate interventions.
Having good, supportive social relationships has been shown to

Having good, supportive social relationships has been shown to 
be a major protective factor in the aetiology and maintenance of many psychiatric disorders. The ability to make and maintain friends—initially of the same age and later of any age—is often related to the existence of disorders such as personality disorders, social anxiety disorders, depression, and even post-traumatic stress disorders. The emphasis on social skills training for socially inade-quate persons points to the early basis for such deﬁ  cits even though 
they may have their greatest impact in adulthood. Some children are less sensitive to social cues than others, and some children mis-interpret the intentions of other people. Both lead to difﬁ  culties, 
albeit of different sorts.
Boys and girls tend to develop different types of social relation-

ships. It may be inconveniently politically incorrect to note that children tend to prefer playing with others of the same gender when freed from adult inﬂ  uence. Boys tend to play in larger, looser 
groups in which issues of dominance and play ﬁ  ghting predomi-
nate; girls relate in smaller groups of more intense relationships, with best friends often changing.
Taking a developmental perspective to mental health issues should apply across the lifespan. Psychiatrists working with adults need to understand where their clients are coming from and where they are going to. They need to understand the pleasures and pressures that children bring to their parents, and where appropriate they should be considering the impact of parental illness on the children. The 2.5.1 developmental psychology through infancy, childhood, and adolescence

SECTION 2  the scientific basis of psychiatric aetiology 244
institutionalized separation of child and adult psychiatry (in terms 
of service delivery) should not lead to a separation in ways of con-sidering the developmental context of presenting problems.
This chapter has shown that there are many small, focused mod-
els of development that deal with discrete areas of development. Stage theories emphasize differences at different stages; social learning theories emphasize continuities on processes of develop-ment. As long as practitioners are aware that when they say a child is at a particular stage, this is but a rough guide to describing the child, which may be ﬁ  ne. It is when such models are taken literally, 
that oversimpliﬁ  cation leads to poor practice. There is no one over-
arching theory of child development and while this may be incon-venient for examiners, it truly reﬂ  ects the rich diversity of human

arching theory of child development and while this may be incon-venient for examiners, it truly reﬂ  ects the rich diversity of human 
development. By paying more attention to the interactions between biological, social, and psychological factors, a better understanding of healthy, normal development will emerge. Empirical studies will help identify risk and protective factors which in turn will lead to better mental health promotion and more effective interventions when mental disorders manifest.
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2.5.2 Psychology of attention
Attention is generally taken to be the process by which people are

Attention is generally taken to be the process by which people are 
able to concentrate on certain information or processes, while ignor-ing other events. It appears to be a fundamental attribute of human brain processing, although difﬁ  cult to pin down in terms of mecha-
nism. Psychologists have attempted to fractionate attention in many different ways, using ingenious behavioural paradigms. In this sec-tion we, too, will consider different aspects of attention: selective, phasic and sustained, divided and executive control of attention. However, it would be fair to say that all these aspects of attention do not normally operate in isolation. Instead they interact, and deﬁ  cien-

cies in one aspect of attention, for example, in a patient population, often to do not occur in isolation. Functional imaging and lesion studies of attention have proliferated in recent years, attempting to place a neurobiological framework to these varied processes. In gen-
eral, these studies also tend to conﬁ  rm the view that attention is like-
ly an emergent property of widespread brain networks, with a special emphasis on frontal and parietal regions of the human brain (Fig. 2.5.2.1). In this discussion we illustrate several aspects of attention with examples particularly from literature on visual attention, which is the most widely studied area, but it should be appreciated that many of the concepts discussed here extend to other domains. In fact, there is a good deal of evidence to suggest that several aspects of attention operate at a supra- or cross-modal level allowing integra-tion of information from different sources.

Recent studies suggest there are two fronto-parietal networks: 
(Fig. 2.5.2.1) a dorsal  parieto-frontal network involving the superi-
or parietal lobe (SPL) and dorsal frontal regions such as the frontal eye ﬁ  eld (FEF); and a ventral  network involving the inferior pari-
etal lobe (IPL), temporoparietal junction (TPJ) and inferior frontal gyrus (IFG). In addition, dorsomedial frontal areas, including the anterior cingulate cortex (ACC) and pre-supplementary area (pre-SMA) may play a key role in ﬂ  exible control of attention for 
strategic behaviour.
Selective attention
Selective attention refers to the processes involved in selecting relevant information and ﬁ  ltering out irrelevant items from the

Selective attention refers to the processes involved in selecting relevant information and ﬁ  ltering out irrelevant items from the 
vast array of information we are exposed to. The brain has limited capacity: it simply cannot process everything it is exposed to. Nor would it be sensible for it do so because the majority of sensory input to which it is exposed is not behaviourallyrelevant. Therefore there is a need for mechanisms to select the 2.5.2 psychology of attention

SECTION 2  the scientific basis of psychiatric aetiology 246
most behaviourally signiﬁ  cant and important material, and dispose 
of trivial, unimportant information. Such selection may occur‘bottom-up’ , driven by competition between sensory inputs, or ‘top-down’ , guided by the goals that an individual might have at any moment in time.
(1)
Thus if a ball is unexpectedly hurled towards an observer, his

(1)
Thus if a ball is unexpectedly hurled towards an observer, his 
attention is likely to be captured—‘bottom-up’—by the sensory input of a projectile moving at high velocity towards his head. In this case, selection has been driven by the most perceptually salient item in the external environment. ‘T op-down’ attention mechanisms, on the other hand, concern selection that is biased by internal goals. For example, consider the processes involved in looking for a friend in a busy, crowded train station. Here the selection process is driven by the features you are searching for: your friend’s hair colour, facial features, height all play a role in guiding this search. Importantly, under these circumstances, even perceptually very salient items may be ﬁ ltered out—or not attended—if they are irrelevant to the task.
But when does selection occur? Is it early or late in the processing

But when does selection occur? Is it early or late in the processing 
of sensory information? This is an issue that dominated attention research for many years. Some investigators proposed that selection occurs early, directly after analysis of the physical characteristics or features of sensory stimuli, but before they are fully identiﬁ  ed. According to this view, unattended information receives little or no 
further processing from this point on. By contrast, others argued that all stimuli are analysed up to the point that they are identiﬁ  ed.

further processing from this point on. By contrast, others argued that all stimuli are analysed up to the point that they are identiﬁ  ed. 
Selection occurs only after this, late in the processing stream. So items that are eventually ignored or unattended, i.e. those that are not selected, actually receive considerable processing before they are discarded. Note that this late selection model allows for the pos-sibility that items which are eventually ignored may nevertheless be processed to a deep level. Thus, even though they may not be attended to, they have the potential to inﬂ  uence our actions sub-
liminally. Most researchers would now agree that there is good evi-dence for both early and late selection systems in the human brain. 
In fact, whether selection occurs early or late is likely to be inﬂ  u-
enced by the speciﬁ  c demands of the task.
Two highly inﬂ  uential experimental paradigms used to study

Two highly inﬂ  uential experimental paradigms used to study 
selective attention in healthy humans and patients have both focused on spatial  attention in the visual system. Posner ﬁ  rst devel-
oped a spatial cueing task in which subjects view a display consist-ing of a central cross on which they are asked to maintain ﬁ  xation

oped a spatial cueing task in which subjects view a display consist-ing of a central cross on which they are asked to maintain ﬁ  xation 
throughout the trial. On either side of the cross, there are two square boxes. Participants are instructed to ignore a cue which consists of transient illumination of either the left or right box. At varying intervals after the cue, a target stimulus (an asterisk) appears in either left or right box and subjects are required to press a response button as quickly as possible. In 80 per cent of trials the cue is ‘valid’ in that it occurred at the location of the subsequent target. However, in the remaining 20 per cent of trials the cue is ‘invalid’ , appearing in the box opposite that in which the target subsequently appeared. In healthy volunteers, reaction times to tar-gets appearing where valid cues appear are signiﬁ  cantly shorter 
than when invalid cues are presented.
This critical ﬁ  nding suggests that attention can be spatially local-

ized like a beam or ‘spotlight’ . Moreover, attention can be captured by the abrupt onset of the cue so that visual processing is selec-tively oriented towards it, thereby improving responses if a target subsequently appears there. On invalid trials, Posner argued, atten-
tion would ﬁ  rst have to disengage from the invalidly cued location

tion would ﬁ  rst have to disengage from the invalidly cued location 
and then shift to the correct location before engaging it. Note that such shifts occur covertly in the absence of overt eye movements; they represent shifts of visual processing from one location to another across a representation of space in the brain. Subsequent studies have shown that the orienting of attention to a spatial loca-tion not only appears to speed up detection of a visual stimulus, as measured by reaction times, but also can improve discrimination of items from non-targets. The neurophysiological mechanisms underlying such boosting of performance are currently the subject of intense scrutiny.
(2)
The second experimental task that has proven to be extremely 
important in selective attention research is the visual search para-
digm developed by Treisman. In this task, subjects have to ﬁ  nd a

digm developed by Treisman. In this task, subjects have to ﬁ  nd a 
target shape embedded among distractors. In simple so-called ‘feature search’ , a target may be deﬁ  ned by a unique feature, e.g. 
a red circle among green circles is deﬁ  ned uniquely by its colour 
and therefore ‘pops-out’ among the distractors. Treisman has considered that such feature searches can occur pre-attentively  in 
parallel across the visual scene, without the need for a spotlight of visual attention. She argued that attention needs to be deployed in more complex tasks where a target may share one or more features with distractors, e.g. ﬁ  nding a red circle among green circles and Fig. 2.5.2.1 Lateral (a) and medial (b) regions in the right hemisphere involved in 
attention. (IPS intraparietal sulcus; MFG, middle frontal gyrus.)
(a)
(b)

247
red squares. In this case, a single feature (colour or shape) is not 
sufﬁ cient to deﬁ  ne the target. Instead, the visual system has to ﬁ  nd 
the unique conjunction of red colour and circular shape, and the target does not pop-out to the observer. Such ‘conjunction searches’ , Treisman argued, requires the spotlight of attention to shift serially from one location to the next, inspecting each item in turn. In her model, spatial attention acts to bind or glue together features occupying the same location in space, e.g. the colour, form, luminance, and other attributes that belong to an object at one location in space.
Both the Posner cueing task and Triesman’s conjunction task 
have been used in neuroimaging studies of healthy volunteers and patients with focal lesions on the brain.
(3) The results of such stud-

ies suggest that regions within the parietal and frontal cortex play a critical role in deploying spatial attention (Fig. 2.5.2.1). In general, dorsal regions of this parieto-frontal network have been implicated in the spatial shifts of processing attention that occupy such a key role in the models of selective attention developed by Posner and Treisman.
Phasic, sustained, and vigilant attention

Several groups have made a distinction between phasic alertness, sustained attention, and vigilance. In general, ‘phasic alertness’ is used to refer to improvements in performance that follow a warn-ing signal, e.g. an auditory tone or visual cue. The tasks used in such studies are often very simple, comparing the time to respond to a particular stimulus when it is preceded, or not, by a warning tone. Over the course of a few hundred milliseconds after such a warning signal, performance can alter appreciably, with reaction times ﬁ  rst declining in the interval from 100 to 500–1000 ms after 
the tone, and then increasing again thereafter. Thus, this attention-al facilitation is limited to a very narrow window in time and refers to the ability of the brain to respond better when warned to expect an upcoming cue to act.
By contrast, ‘vigilance’ is the term used to refer to the ability to be

By contrast, ‘vigilance’ is the term used to refer to the ability to be 
in a state of readiness to detect small, infrequent changes in the environment which occur at random intervals over prolonged
periods of time (often hours or tens of minutes). The early studies on vigilance were conducted to assess the ability of radar operators to detect infrequent signals on their screens in the Second World War. Over long ‘vigils’ the ability to detect rare changes falls—the so-called ‘vigilance decrement’—and this may be modulated by the frequency of target and non-target (distractor) stimuli as well as the memory load imposed on observers.
‘Sustained attention’ is best considered to be at the other end of 
the continuum from vigilance. Here, too, observers may have to respond over a prolonged period, but the information ﬂ  ow is rapid,

the continuum from vigilance. Here, too, observers may have to respond over a prolonged period, but the information ﬂ  ow is rapid, 
with a high frequency of events to monitor and respond to. An everyday, extreme example may be the interpreter who has to give a simultaneous translation of a press conference. In the laboratory, sustained attention may be studied using stimuli presented at a rapid rate, as in many continuous performance tests (CPTs). Such experiments reveal that even healthy subjects may show ‘lapses of attention’ under such circumstances, with errors of omission (fail-ing to respond to a target stimulus) or errors of commission (responding to a non-target), or increase in mean response time. Another measure that has attracted interest, of late, particularly in patient populations, is the variability of reaction times in such tests.Functional imaging and lesion studies of patients have empha-

sized the role of the right lateral frontal lobe in aspects of vigilance and sustained attention. However, it is clear that the inferior pari-etal lobe of the right hemisphere also has a critical role to play in these functions. The distinction between frontal and parietal con-tributions remains to be established but, unlike spatial attention studies, investigations of non-spatial vigilance and sustained atten-tion suggest that ventral —and not dorsal—frontal and parietal 
regions of the right hemisphere have a special role in these processes (Fig. 2.5.2.1).
(4)
Divided attention
Divided attention is the ability to concentrate on more than one activity at once. Although we often execute two tasks simultane-ously (‘dual task’), performance on one or both tasks may be impaired compared to doing either alone, e.g. when driving and having a phone conversation. Experimental ﬁ  ndings that demon-

strate such decrements in performance raise important questions regarding the mechanisms underlying attention. Many investiga-tors have proposed that if a second task leads to deterioration in performance of the ﬁ  rst, one may conclude that the two tasks 
depend on the same brain resources. Because such resources are limited, there will be a decrement in performance once resource limits are reached. Some authors have argued for a single, central resource while others have presented evidence for multiple 
resources, but the basic concept is the same across these accounts: 
tasks compete for ﬁ  nite brain resources and if they share those 
resources, performance suffers.
Other investigators have raised the possibility that it is not just 
‘resources’ that we need to consider but also processing limitations. Two tasks might be difﬁ  cult to perform simultaneously because

‘resources’ that we need to consider but also processing limitations. Two tasks might be difﬁ  cult to perform simultaneously because 
they both use a single processing channel or because the tasks inter-fere with each other. Different paradigms have suggested ‘bottle-necks’—mechanisms that are dedicated serially to only one task at a time or have limited resources to spread over two tasks. Such bot-tlenecks may exist at the level of attentional focus, storage in visual short-term memory (VSTM), and motor preparation.
(5) Consider 
ﬁ rst the issue of processing bottlenecks.
The attentional blink paradigm is used to investigate temporal 
limitations of attentional processing. Subjects view a stream of individually presented letters and are required to report when they see either of the two target letters (say X and Y). People generally struggle to report a second target if it falls within 360 ms of the ﬁ rst, despite being able to report the second target when not

attending to the ﬁ  rst. Processing the ﬁ  rst object before being free to 
process the next item appears to require up to 360 ms. Thus speed of attentional processing may act as a limiting factor in dual task processes. Functional imaging studies suggest, once again, that a fronto-parietal network is critical in this regard. Activity in fronto-parietal areas occurs only when the second stimulus is reported. 
In contrast, even when the second stimulus is undetected, there 
is still activity in the early visual areas. These ﬁ  ndings point to a 
bottleneck in attentional processes which occurs after basic visual processing has begun, but before conscious perception, consistent with pre-attentive and attentive stages of visual processing as discussed in the section on selective attention above.
The amount of information we can encode at any one time is

The amount of information we can encode at any one time is 
also limited. The capacity for holding objects in visual short-term memory (VSTM) is around four objects. Diversion of attention 2.5.2 psychology of attention

SECTION 2  the scientific basis of psychiatric aetiology 248
away from an object reduces the accuracy with which it can be 
encoded suggesting that attention is an important limiting factor in the number of items held in VSTM. Both electrophysiological and functional imaging experiments have suggested that the capac-ity for storage of objects in VSTM is related to posterior parietal and occipital cortex activity.
As well as these perceptual and memory limitations in capacity,

As well as these perceptual and memory limitations in capacity, 
there are limits at the motor selection stage of processing. The psy-chological refractory period (PRP) refers to the delay in the second response when a subject has to respond to two stimuli one after the other. The shorter the time difference between the two stimuli, the greater the delay in the second response. This bottleneck may be at the level of response selection rather than a pure perceptual or attentional slowing. However, although it is often the case that per-forming two simultaneous responses with a single effector (e.g. the hand) may be impossible, the PRP cannot simply be explained in terms of a motor selection bottleneck.
When subjects are asked to make two responses to the same 
attribute of an object (name the colour and press a button for the

attribute of an object (name the colour and press a button for the 
colour), they can select the appropriate responses at the same time. In addition the PRP is much longer when required to make an incongruent response (e.g. saying ‘A ’ in response visual presenta-tion of the number 1) than a congruent response (e.g. saying ‘one’ in response to visual presentation of number 1) to the second stimulus. Pashler has proposed that at any time we have a number of response selection rules, with each rule specifying condition-action linkages or associations, i.e. which condition is associated with which action. According to this view, the bottleneck is at the level of rule application, but each rule can specify multiple motor responses.
But how and where rules are selected and maintained?

But how and where rules are selected and maintained? 
Many studies have suggested a critical role for frontal—so-called ‘executive’—control systems when rules need to be applied, as we shall discuss in the next section. Performing two  well learned  or 
relatively automatic  tasks together might not lead to performance 
impairment because these tasks do not require input from such ‘executive’ control systems to implement rules and select appropri-ate responses.
In summary, there are multiple possible levels at which processing

In summary, there are multiple possible levels at which processing 
capacity may be limited. Both the speed of attentional processing and the number of items that can be attended to at once and held in memory are limited. In addition, supervisory or executive con-trol regions may regulate motor output perhaps by implementing goals or strategies. Whether these bottlenecks are due to one resource being serially applied to each stimulus or a limited capac-ity system shared simultaneously by two processes, but perhaps with a bias toward one, is currently unclear.
Executive control of attention
How are the subtypes of attention mentioned above organized so that they are activated at the appropriate time? Events in our envi-ronment reﬂ  exively engage attentional networks and this type of

How are the subtypes of attention mentioned above organized so that they are activated at the appropriate time? Events in our envi-ronment reﬂ  exively engage attentional networks and this type of 
stimulus-driven or bottom-up activation may underlie some pro-cesses such as rapid shifts in spatial attention to highly salient events. However, everyday experience tells us that rather than always reacting to our surroundings, we are able to generate and implement plans to complete complex tasks and sometimes ignore highly salient events. This has led to the idea of a supervisory or executive attentional control system. Evidence for the presence of such a system comes from patients with brain damage, particularly those with frontal damage.
Patients with frontal lesions have difﬁ  culty maintaining atten-
tion on a task. They may be highly distractable, or ﬁ  nd it difﬁ  cult to 
divide attention between competing task demands in an optimal

divide attention between competing task demands in an optimal 
way. Some patients also encounter problems shifting from one task 
type or task rule to another, often demonstrating perseveration—
Fig. 2.5.2.2 In the Wisconsin card 
sorting test (a), the patient has to place a new card alongside one of the visible cards according to a rule to match colour, suit or number. The 
rule changes during the task and the 
learning occurs by trial and error. Patients with frontal lobe damage fail to update the new rule. The Stroop task (b) requires subjects to give the colour of the text. In the ﬁ  rst box this is easy because the colour of the text and the meaning of the word are 
congruent (both red). The second and

congruent (both red). The second and 
third boxes illustrate the incongruent condition. This is more difﬁ  cult because the text colour is different from the meaning of the word. Normal individuals are slower to respond in the incongruent than congruent conditions.
(a) (b)

249
applying the ‘old’ task rule inappropriately when they should be 
applying the ‘new’ one. For example, on tasks such as the Wisconsin card sorting task, where subjects establish the criteria for grouping playing cards into sets (according to either colour, or suit, or number) and then have to change to a new grouping rule, such individuals have great difﬁ  culty shifting to a new rule (Fig. 2.5.2.2a). Multiple 
components of executive control including ﬂ  exible task-switching 
and response inhibition, as well as vigilance and error monitoring, are required to successfully sort the cards when the rule is switched.
Norman and Shallice developed a model of attention control

Norman and Shallice developed a model of attention control 
called the supervisory attention system that conceptualized how this behaviour might be organized. They proposed that routine or well-learned behaviour occurs because perceptual information activates a set of schemas that then triggers appropriate motor out-put. However, these perceptual-motor associations would no lon-ger be appropriate when the rule changed, for example when one had to sort according to suit rather than number in the Wisconsin card sorting task (Fig. 2.5.2.2a). Under these circumstances, they proposed that the supervisory attention network alters the bias of the schemas so that different motor outputs are triggered by per-ceptual events. Therefore, rather than processing simple stimulus-response associations such as always signalling the right foot to move from the brake to the accelerator when a green trafﬁ  c light

appears, brain regions within the supervisory network would respond to information at a more abstract level. When driving, for example, one might want to inhibit  the prepotent response associ-
ated with the green trafﬁ  c light (to press the accelerator) if confronted 
by a variety of visual inputs such as someone still crossing the road or a car stalled in front. Response inhibition  in this and other 
contexts is thought to be one of many abstract functions under-taken by the supervisory control systems.
What are these abstract processes and which regions of the brain

perform these supervisory operations? Both lesion studies and functional imaging work have contributed to understanding exec-utive functions. Functional imaging studies provide information about areas activated in association with certain processes while lesion investigations show which regions are critical for normal behaviour. In paradigms such as the Stroop task, subjects are asked to report either the colour of print used to type a word or read the word which can be the same (congruent) or a different (incongruent)colour to the print (Fig. 2.5.2.2b). T o avoid making errors in the incongruent condition one is required to focus attention on the target information and suppress the unwanted response. This is usually associated with a reaction time delay in the incongruent compared to the congruent condition. The delay is greater when subjects have to report the colour of the print and inhibit their reading of the word, presumably because word reading is a more hard-wired or automatic

congruent condition. The delay is greater when subjects have to report the colour of the print and inhibit their reading of the word, presumably because word reading is a more hard-wired or automatic than colour naming. Functional imaging and lesion data from subjects performing the Stroop tasks show that medial and lateral frontal as well as parietal areas appear to form a network for executive control of attention.

There is recent evidence that each of these regions has a distinct 
role within the executive control network. Speciﬁ  cally, the left 
lateral frontal cortex is thought to maintain and ﬂ  exibly update 
task rules, whereas, right lateral prefrontal cortex is critically involved in inhibiting  the prepotent response associated with a 
stimulus. Dorsomedial frontal regions (Fig. 2.5.2.1b) reliably acti-vate when executive control is required and are thought perhaps to play a key role in monitoring errors. In addition, part of this area—the anterior cingulate cortex—is considered by some investigators to be important for mediating the physiological autonomic response to demanding circumstances. More posterior regions including parietal cortex, may also contribute to attentional con-
trol but, to date, their role has been less well investigated. Research into how areas involved in executive control act and interact to

trol but, to date, their role has been less well investigated. Research into how areas involved in executive control act and interact to 
modulate attention is a rapidly expanding area of cognitive neuro-science, likely to yield important insight into mechanisms behind ﬂ exible and efﬁ  cient behaviour.
This work is funded by the Wellcome Trust.
Johnson, A. and Proctor, R.W. (2004). Attention theory and practice .
Sage Press, California.
Styles, E.A. (2006). The psychology of attention .  (2nd edn). Psychology Press, 
New Y ork.
Ward, A. (2004). Attention a neuropsychological approach . Psychology Press, 
Hove.
1. Desimone, R. and Duncan, J. (1995). Neural mechanisms of selective 
visual attention. Annual Review of Neuroscience ,18, 193–222.
2. Treue, S., (2001). Neural correlates of attention in primate visual 
cortex. Trends in Neurosciences ,24(5), 295–300.
3. Corbetta, M. and Shulman, G.L. (2002). Control of goal-directed and

3. Corbetta, M. and Shulman, G.L. (2002). Control of goal-directed and 
stimulus-driven attention in the brain. Nature Reviews Neuroscience ,
3, 215–29.
4. Husain, M. and Nachev, P . (2007). Space and the parietal cortex. Trends 
in Cognitive Sciences ,11, 30–36.
5. Marois, R. and Ivanoff, J. (2005) .Capacity limits of information 
processing in the brain. Trends in Cognitive Sciences ,9, 296–305.
2.5.3 Psychology and 
biology of memory
Andreas Meyer-Lindenberg 
and Terry E. Goldberg
Memory in psychiatric practice
Memory is the ability to store, retain, and retrieve information. 
This cognitive function plays a key role in psychiatry. Dementia and the amnesic disorders have memory dysfunction as a deﬁ  ning

This cognitive function plays a key role in psychiatry. Dementia and the amnesic disorders have memory dysfunction as a deﬁ  ning 
feature. Intrusive and recurrent emotional memories are one of the most distressing symptoms in post-traumatic stress disorder. Although not as obvious, problems with memory are also com-monly revealed on testing in schizophrenia. Remembered episodes are often a focus in psychotherapy, as is the acquisition of new habits and response patterns. An ability to understand and assess memory is therefore important for the practising psychiatrist. In this chapter, basic neurobiological and psychological information 2.5.3 psychology and biology of memory

SECTION 2  the scientific basis of psychiatric aetiology 250
on memory will be reviewed. We have tried to cover a very broad 
field in a concise manner and give the interested reader a sense of the key memory systems and subsystems that are thought to be important for human information processing in health and in disease. We have emphasized the conceptual over the theoretical and key ﬁ  ndings over the experimental details where possible. 
At times, we have not carefully separated the cognitive and neuro-anatomical levels of analysis, both because they are sometimes almost inextricably bound and because it made our explanations clearer not to do so. Necessarily but not happily, we have omitted many important and active areas of investigation.
Forms of memory
One of the key discoveries of cognitive neuroscience is that ‘memo-ry’ is not an unitary function, but consists of several forms that can be dissociated neurally and are differentially impacted by psychiat-ric disorders.

(1) Several approaches can be taken to subdivide 
memory. One of the most straightforward is by the duration over which information is retained. In this way, ultrashort-term, short-term, and long-term memory can be distinguished. Ultrashort-
term , also called sensoric  or echoic/iconic  memory, lasts from 
milliseconds to seconds and consists of a brief and modality-speciﬁ  c retention of sensory information. For example, most peo-
ple are able to ‘replay’ the auditory trace of the last second or so of a conversation, or brieﬂ  y maintain a scene visualized after they 
close their eyes. In contradistinction, short-term memory  has been 
shown to be relevant to a large number of psychiatric disorders. In short-term memory, information is brieﬂ  y (over a period from 
seconds to minutes) held in mind, often through a process of rehearsal. A typical example is remembering a phone number from reading it to dialing without writing it down. A key feature of short-

term memory is capacity limitation: most people are able to retain 
about seven items in short-term memory.
(2) A speciﬁ  c form of 
short-term memory that has received considerable interest is work-
ing memory : the ability to hold information in mind that is neces-
sary for a task at hand, but not present in the environment. This faculty is often regarded as a ‘mental workspace’ that is critical for information manipulation and goal-directed adaptive behavior, and the association of working memory with speciﬁ  c brain systems 
and psychiatric disorders has been widely studied. Rehearsal is also one important mechanism by which material is being transferred into long-term memory , which refers to the ability to retain infor-

mation for time periods lasting from minutes up to the life span of the individual. This form of memory, which is also of major clini-cal importance, is not clearly capacity limited and is thought to depend on more enduring changes in neuronal structure and con-
nectivity, raising the question of where in the brain these enduring 
memory traces, or ‘engrams’ , are stored, how they are encoded for storage and how they are retrieved from it.
A second important subdivision is whether the content of mem-
ory can be consciously and intentionally retrieved (this is called explicit or declarative  memory) or not (nondeclarative or implicit
memory) ( Fig. 2.5.3.1 ). Declarative memory is further subdivided in 
memory of facts and memory of events. Memory of events, which often includes recollection of temporal, spatial and emotional circumstances, is called episodic  memory. Questions such as ‘What

memory of facts and memory of events. Memory of events, which often includes recollection of temporal, spatial and emotional circumstances, is called episodic  memory. Questions such as ‘What 
did you have for breakfast this morning?’ or ‘Where did you go to school?’ access episodic memory. Several features of episodic mem-ory bear mention for their clinical relevance. For example, people can often say that they have seen a speciﬁ  c item before or that 
it ‘feels familiar’ without being able to recall the specifics of where and when (the episodic context). As discussed below, some evidence suggests that familiarity and recall may be supported by different brain regions. Intense feelings of familiarity without recall are experienced as déjà vu  in a psychiatric context. People can also 
be convinced to remember events that did not, in fact, happen. These so-called false memories  are also encountered in psychiatry.

be convinced to remember events that did not, in fact, happen. These so-called false memories  are also encountered in psychiatry. 
There has been much work on paradigms that produce false mem-ories in normal individuals that address how they develop and how and why they might be successfully rejected. In one canonical account of episodic memory, the medial temporal lobe system (MTL) stores or indexes contextual markers that serve to bind fea-ture information of a memory into an episodic conﬁ  guration.
In contradistinction to episodic memory, memory of facts is not 
connected to speciﬁ  c experience. It is called semantic  memory, and

connected to speciﬁ  c experience. It is called semantic  memory, and 
recollection of facts or vocabulary are examples of information that has become independent of episodic memory. Over time such material is thought to be stored in neocortex and can be retrieved without engagement of medial temporal lobe structures (MTL). Various models of the distinctions between semantic and episodic memory have proposed that while learning in the episodic system is rapid and can be based on a single trial or exposure, storage of information in the semantic system occurs slowly over time and only after multiple exposures or activations 
(3). Some accounts 
suggest that the MTL may also be involved in semantic memory, for example for separation or ‘decompression’ of stimuli previously learned as a unit.
(4, 5) We have chosen not to review semantic mem-

ory in further detail because of space limitations and its complex overlap with psycholinguistics.
Whereas the subdivision of declarative memory is comparatively 
simple, implicit memory encompasses quite a heterogeneous group of functions that are supported by different brain systems. Among them are procedural memory , which refer to the gradual acquisi-
tion of sensorimotor, perceptual or cognitive skills through repeated exposure, priming  (the facilitation of a response to an item if it was 
previously encountered), conditioning  as well as various phenom-
ena wherein a previously acquired response is gradually reduced or lost, such as extinction . Since the distinction between declarative

ena wherein a previously acquired response is gradually reduced or lost, such as extinction . Since the distinction between declarative 
and implicit depends on whether or not a memory process supports conscious recollection, clinicians must be careful not to 
confuse this with the properties of a given neuropsychological test; 
for example, a test of sentence completion requires conscious 
Fig. 2.5.3.1 Classiﬁ  cation of memory and associated neural systemsLong Term Memory
Explicit
(Declarative)
Facts
(Semantic)Events
(Episodic)PrimingProcedural
(Skills and Habits)Conditioning
and Extinction
Medical
Temporal LobeNeocortexStriatum
CerebellumAmygdalaImplicit
(Nondeclarative)

251
production of words, but performance may strongly depend on 
implicit processes such as priming.
Although a taxonomy of memory systems is useful, many 
everyday tasks require functionality from several memory domains, and even relatively subtle changes in task demands may disrupt the balance among those cognitive systems. More reﬁ  ned analysis of 
learning tasks suggests that a variety of learning systems may medi-ate performance,
(6) and that a given neural system participates in 
several forms of memory. For example, the hippocampal forma-tion (HF), which is critical for episodic memory, is also thought to play a role in learning sequences so that indirect relations can be speciﬁ  ed.
(7) Thus, the HF becomes critical not during a >b, b>c, 
and c >d discriminations, but for the discrimination of the critical 
indirect b >d probe (e.g. if John is taller than Bill and Bill is taller 
than Mary and Mary is taller than Ellen, then Bill must be taller than Ellen).

Cellular and molecular mechanisms of memory
Memory is one of the most impressive examples of neural plastic-ity: the ability of the nervous system for enduring change trig-gered by external events. Arguably the best-studied cellular mech-anisms underlying plasticity are long-term potentiation (LTP) and long-term plasticity (LTD), which mediate enduring changes on the level of the synapse.
(8) Both have been best characterized 
in the hippocampus, one of the key structures for declarative memory.
By stimulating presynaptic ﬁ  bres in the hippocampus (especially

By stimulating presynaptic ﬁ  bres in the hippocampus (especially 
the CA1 section) with a brief pulse of high-frequency electric impulses, a long-lasting increase in responsiveness of the postsynaptic cells to low-frequency stimulation is reliably observed that can last for weeks (Fig. 2.5.3.2) . This is called LTP . Initiation of this process 
depends on multiple second messenger mechanisms ( Fig. 2.5.3.2 ). 
One of the best studied pathways starts with calcium inﬂ  ux into the 
presynapse through a glutamate receptor, NMDA, which activates further molecular cascades involving cAMP and protein kinases such as CamKII (other receptors, such as the glutamate receptors AMPA and mGluR, also play a role). LTP is then maintained by 
changes in gene transcription factors, such as CREB, and changed

changes in gene transcription factors, such as CREB, and changed 
patterns of protein synthesis and phosphorylation, probably also dependent on protein kinase cascades. The time course of these processes can be used for a distinction between early phase LTP (the cellular signature of learning that occurs over seconds to min-utes) and late phase LTP , which involves protein synthesis and occurs over minutes to hours and is thought to be critical for con-solidation of new memoranda and would be linked to memory consolidation.
(9,10)
LTD is a closely related process that is triggered when presynaptic 
stimulation is lower, causing less calcium inﬂ  ux (again through

(9,10)
stimulation is lower, causing less calcium inﬂ  ux (again through 
NMDA receptors) and preferential activation of calcineurin, a pro-tein phosphatase. T ogether, LTP and LTD allow bidirectional enduring modulation of synaptic strength that could underlie formation and reversal of experience-dependent coupling in neural assemblies. Linking these synaptic changes to validated mechanisms underlying the complexities of human memory remains a challenge. However, the active ﬁ  eld of neural network 
modeling has shown that, in principle, such changes in synaptic efﬁ cacy can produce efﬁ  cient mechanisms to encode, store and 
retrieve information, a proposal ﬁ  rst made by the neurophysiologist 
Donald Hebb.Declarative/episodic memory
(a) Neural systems

Current evidence indicates that the HF and linked regions of the medial temporal lobe (MTL), in interactions with parts of the pre-frontal cortex, play a critical role in the encoding and retrieval of episodic memories, whereas engrams are stored in neocortex
(11)
(Fig. 2.5.3.3 ). Interactions of the HF with amygdala are important 
for emotional memories. The HF consists of the hippocampus proper, the entorhinal cortex, which provides the main port of entry for connections with the cortex, and the adjacent perirhinal and parahippocampal cortices, which interact with the entorhinal cortex and in turn receive projections from all other neocortical areas, with parietal, dorsal occipital and prefrontal regions primar-ily projecting to parahippocampal gyrus and temporal cortex to Fig. 2.5.3.2 Top: Long-term potentiation after a tetanic stimulation in the HF.

Bottom: molecular mediators of long-term potentiation.
0.4A
B1. Control
Mg2+
Ca2+
Phosphatases
Protein
kinases
PLCDAG
G P
mGIuRPLTD
LTPCa2+
Ca2+
[Ca2+]
Ca2+
IP3Ca2+
storesPVGCC
NMDA
AMPA
VGC C90 min Superimposed B2 B3Tetanus
0.2Slope (mV/ms)
0.0
0 30 60 90 1202.5.3 psychology and biology of memory

SECTION 2  the scientific basis of psychiatric aetiology 252
perirhinal cortex. In this way, the HF is bidirectionally connected 
with the rest of the brain. Although pertinent observations were already made at the end of the 19th century by Bechterew, the importance of the hippocampal formation for episodic memory was dramatically shown in 1953 by the case of patient H.M., in whom the HF and amygdala were resected bilaterally as a treatment for drug-resistant epilepsy
(12) (Fig. 2.5.3.4 ). This led to complete 
and enduring anterograde  amnesia (inability to form new episodic 
memories). In addition, he has some degree of retrograde  amnesia

memories). In addition, he has some degree of retrograde  amnesia 
(i.e. an inability to retrieve episodic information stored before the operation), while his working and procedural memory, as well as priming, is unimpaired. A similar pattern of memory impairment is observed in Wernicke encephalopathy/Korsakov’s syndrome or other neurological processes impacting on diencephalic structures, including the medial thalamus, mamillary body and the fornix, which project to the HF. This indicates that these structures may be viewed as a system that is critical for assigning a spatiotemporal (episodic) context. In rodents, a major role of the HF is indeed to function as a neural map of the environment;
(13) it is controversial 
to what degree this applies to humans. Neuroimaging studies conﬁ  rm that activation of the HF is observed during successful

to what degree this applies to humans. Neuroimaging studies conﬁ  rm that activation of the HF is observed during successful 
encoding and retrieval of episodic information.
(14)
A neurocognitive model system for examining the computational 
role of MTL subsystems involved in episodic memory may help the reader gain a sense of the interplay among various subprocessing modules.
(15) In this model, the MTL binds memories and their 
instance-speciﬁ  c context and then stores their code for later retrieval.

instance-speciﬁ  c context and then stores their code for later retrieval. 
The model described here is based on studies showing that the bulk of hippocampal (HC) cortical input is segregated over two pathways. One of these may convey spatial information; the other may convey information regarding items and objects. The two streams are interconnected at various levels within entorhinal cor-tex, which likely contributes to the integration of cortical inputs into a representation of their co-occurrence. The hippocampus proper may quickly associate a code to the conjunction of cortical inputs, such that similar entorhinal patterns come to be separated via their associated hippocampal patterns. These hippocampal pat-
terns are thus not directly associated with individual features, but serve to separate the large number of overlapping entorhinal pat-

terns, which is important to ensure that retrieval will be unambig-uous. The representational overlap in entorhinal cortex, combined with the pattern separation system in the hippocampus proper, enormously increases the storage capacity of the memory store and allows accurate recall of episodic memories. In this model, retrieval in this memory system can be sampled using cues, consisting of partial  input patterns; for instance, part of a context representation 
from a previously experienced episode. Initially, such a cue may activate only part of an associated entorhinal pattern, but if the set of activated entorhinal nodes sufﬁ  ciently resembles a stored represen-
tation, their combined ﬁ  ring will tend to activate associated hip-

pocampal nodes, through previously strengthened connections with these nodes. The hippocampal nodes, in turn, will recruit missing nodes of the entorhinal representation. This pattern com-pletion process will reinstate the original pattern in the entorhinal layer, which, in turn, can reinstate associated information in the input layers, namely, item representations that have been experi-enced in that particular context (feature extraction). Thus, all features of an episode can be recalled, even when only part of the input layers is cued.
The model was shown to be sensitive to various types of simu-
lated lesions including reductions of nodes (‘neurones’), addition of noise to the system, and perhaps most relevant for the modeling of schizophrenia, marked reductions in connectivity between the various modules. At the network level, this reduced connectivity

led to compromised cross-association of episodic features (i.e. item 
and context) and a superimposed, mild reduction of pattern separation in the system. The latter malfunction made some Fig. 2.5.3.4 Hippocampal damage in patient H.M., shown on a sagittal (top) and 
two coronal slices (below) of the patient’s MRI.
Fig. 2.5.3.3 (A) brain regions associated with dysfunction in episodic memory. 
(B) the hippocampal formation, view from below. (C) coronal section through the hippocampal formation.
(A) Brain  areas  associated  with declarative
 memory  disorders(B) Ventral  view of hippocampus  and related
 structures  with part of temporal  lobes  removed
(C) Hippocampus  in coronal  section
Optic  tractTail of
the caudate
nucleus
Inferior  horn
of the lateral
ventricle
HippocampusHippocampal
fissure
Inferior  portion
of the temporal
lobeThalamus Fornix
Basal
forebrain
Prefrontal
cortex
Mamillary
body
AmygdalaRhinal
cortexHippocampusOptic  nerve
Mammillary  body
Fornix
Corpus  callosum

fissure
Basal
forebrain
cortex
Mamillary
body
Fornix
Hippocampus
Lateral
ventricle
Temporal
lobe

253
patterns irretrievable, affecting all memory tasks including recog-
nition, albeit to a mild degree. The cross-association problem also attenuated ‘searching’ of the memory store, particularly with single-source cues. This preferentially affected tasks with a large retrieval demand, such as free recall. From an information process-ing standpoint, what appeared to be disproportionate failures in retrieval were due to compromised encoding.
Recent work has indicated that recollection is predominantely 
mediated by the hippocampus proper, whereas familiarity has been linked to perirhinal cortex.
(16) While this distinction is supported 
by functional neuroimaging studies of healthy individuals (e.g. Eldridge et al.
[17]), studies of patients with circumscribed lesions of 
the hippocampus have nevertheless found severe familiarity-based recognition memory impairments.
(18) These results do not neces-

sarily contradict a dual process distinction, but could rathersuggest that MTL regions comprise an integrated network that supports both processes.
There has been much interest in the precise role of episodic 
memory systems in the formation of associations between items that are entering memory. Several new studies suggest that the hip-pocampus is engaged preferentially when inter-item associations are formed in memory. While there have been several compelling accounts that speciﬁ  c subsystems in the MTL complex play different 
roles in single item encoding and associative encoding, the distinc-tion between the two may be relative, not absolute.
(11, 19)
Neuroimaging and lesion studies have suggested that interac-

(11, 19)
tions between the HF and the amygdala are relevant for emotional memories, especially if these have a fearful or aversive character.
(20)
Neuroimaging has also demonstrated that encoding and especially retrieval is associated with activation of the lateral prefrontal cortex, as well as with increased functional interactions of these regions with the HF that are supported by anatomical tracts such as the uncinate fascicle. In some studies, left prefrontal cortex is dif-ferentially more involved than right in encoding information into episodic memory, whereas right prefrontal cortex is differentially more involved than left in episodic memory retrieval.
(21) Compared

(21) Compared 
to encoding and retrieval, the evidence is much less clear with regard to the storage of the engrams themselves. Cases such as H.M. and the clinical picture of Korsakov’s syndrome show that the HF and diencephalic structures cannot be the store, since most episodic and semantic memories laid down before the onset of illness are spared. Current evidence suggests that the neocortex is the ultimate store of memories and that engrams reside in regions that are also specialized in processing stimuli to which they pertain. For example, circumscribed cortical lesions can result in category-speciﬁ  c impairments in retrieving object information, the so-called 
anomias, which have been described for classes such as people, tools, or living things, and neuroimaging studies show that similar regions are differentially activated during naming of these object 
classes. In each case, engrams are assumed to be stored in a distrib-

uted pattern of synaptic connections over a large group of neurones. It is an open question how the interaction of the HF and cortex accomplishes the encoding, and retrieval of information from these neural assemblies (but see above for a model). On the molecular level, glutamatergic neurotransmission is crucial to support the LTP mechanisms that support the neural plasticity essential for memory formation. In addition, acetylcholine is a neurotransmitter associated with declarative memory function since it is known that muscarinic receptor blockade impairs episodic memory and degeneration of cholinergic neurones in the basal nucleus (of 
Meynert) is a prominent ﬁ  nding in Alzheimer’s disease. It is likely 
that cholinergic mechanisms act on declarative memory by modu-lating glutamate-dependent LTP and LTD in MTL regions.
(b) Assessment and neuropsychology

Clinical assessment of memory systems is an important facet of neuropsychiatric and neuropsychologic test batteries. Assessments may vary widely in their depth and breadth and systematic approach. There are numerous tests of episodic memory that can be used for clinical purposes. Well known batteries include the Wechsler Memory Scale-III, which involves verbal memory for stories, verbal paired associates, and word lists, and visual memory for scenes, faces, and designs. Immediate and delayed recall of these tests is assessed. There are also many standardized verbal list learning tests that involve differing degrees of semantic relatedness among words (and perhaps requiring different degrees of strategic encoding) and minor differences in administration. These include the California Verbal Learning T est, the Hopkins Verbal Learning T est, and the Selective Reminding T est. These tests have alternate but equivalent

forms that reduce practice effects when tests are administered 
repeatedly. A comprehensive evaluation of memory should include multiple trials of a word list to assess learning rate or slope; mea-sures of immediate and delayed memory (e.g. recall after 30 min-utes); a recognition test in which a subject must decide whether an item had been studied or not (was old or new in order to minimize effortful retrieval); and tests of visual memory and verbal memory that preferentially engage the right or left MTL systems, which are thought to be material speciﬁ  c, at least to some degree.
Cognitively, there are several distinctions or processes in episodic 
memory that bear special comment. Most are still being actively investigated. One of the earliest and best replicated ﬁ  ndings in pro-
cessing oriented theories of memory suggests that the level at which an item is encoded is an important predictor of later recall.
(22) Thus, words that are encoded deeply (for example, after

(22) Thus, words that are encoded deeply (for example, after 
a semantic judgment about animacy) are remembered better than words encoded superﬁ  cially (for example, after a judgment about 
whether the word contains a speciﬁ  c orthographic feature). The 
exact cognitive mechanism by which this occurs is unclear, but could involve the creation of more cue-item associations so that a wider variety of different searches might have yield.
Another important area involves the distinction between a sense

Another important area involves the distinction between a sense 
of familiarity with an item at recall versus the recollection of an item, which implies knowledge about the spatiotemporal context in which the item was encoded. It is thought that memories may be retrieved through either of these two processes: recollection of a memory that involves adjunctive contextual information; or the feeling of knowing that an item, face, thing, etc. has been encoun-
tered before without memory of the surrounding context.
(23,24)
Rate of forgetting reﬂ  ects the degree to which memories that

(23,24)
Rate of forgetting reﬂ  ects the degree to which memories that 
were once successfully retrieved can no longer be retrieved after a delay. For healthy individuals savings (the inverse of rate of for-getting) may be at 80–90 per cent for several hours or more after initial recall. Several amnesic conditions, as well as a form of frontal temporal dementia, have been associated with increased rates of forgetting. In Alzheimer’s disease and Korsakov’s syndrome, sav-ings may be less than 50 per cent after delays of several minutes. Nevertheless, the situation is undoubtedly more complex psycho-metrically and cognitively than presented here.
(25,26)2.5.3 psychology and biology of memory

SECTION 2  the scientific basis of psychiatric aetiology 254
Implicit memory
(i) Procedural memory
Clinical experience shows that the acquisition of new visuomotor 
skills is often unimpaired in patients with deep amnesia due to medial temporal lobe lesions. Conversely, skill learning, but not declarative memory, is often impaired in patients with degenerative or vascular lesions of the basal ganglia (for example in Huntington’s) or cerebellum. Neuroimaging has conﬁ  rmed the importance of 
basal ganglia and cerebellum for procedural memory
(1) and has 
also demonstrated time-variant activation of primary and second-ary motor cortex during skill learning. The basal ganglia receive excitatory glutamatergic projections from the cortex and thalamus, integrate them with monoaminergic inputs and sends them via the globus pallidus and substantia nigra pars reticulata to the thala-mus, which projects back to prefrontal cortex.
(27) These parallel

(27) These parallel 
processing loops are critical for the integration of sensorimotor, cognitive and emotional information.
(27) It is usual to distinguish 
between a dorsal and a ventral subdivision of the striatum, and it is the dorsal striatum (caudate nucleus, putamen and globus pallidus) that is strongly interconnected with cortical areas relevant for motor planning and execution. The learning of repetitive sequence, as well as so-called ‘open loop’ tasks, in which visual feedback is delayed, especially depends on the integrity of the dorsal striatum and its interactions with cortex.
(28) This extends to skills that are 
not motor, for example the prediction of probabilistic sequences or the planning of complex tasks. Conversely, the importance of the cerebellum lies with ‘closed loop’ tasks that require continuous visuomotor feedback, as well as fast error control. The cerebellum has also been proposed to play a role in creating new stimulus-response mappings.
(ii) Priming

Neuroimaging suggests that the neural substrate of priming lies in neocortex. Speciﬁ  cally, a reduction of activation to a primed 
stimulus is consistently found, either in modality-speciﬁ  c regions 
(such as visual areas for visual repetition priming) or in ‘amodal’ cortical areas such as lateral temporal cortex for semantic priming. It has been hypothesized that this reduced activation represents neural assemblies that are optimized, by ‘pruning’ of unnecessary connections, for easier activation, and that this may underlie the facilitated response to a primed stimulus.
(29) Clinically, this leads to 
the prediction that priming should be altered in disorders that impair the integrity of the cortical regions involved, such as semantic priming in Alzheimer’s disease.
(iii) Fear conditioning and extinction

Conditioned fear is of high relevance in psychiatry in disorders ranging from simple phobias and generalized anxiety disorder to major depression. In conditioning, a fear response to an uncondi-tional stimulus (for example, an electric shock) is transferred to a conditional stimulus with which it is paired (CS, for example, a tone regularily preceding this shock). A large body of research has established a key role for the amygdala in this memory process.
(30)
Different subnuclei of this complicated structure are implicated in establishing and storing fear conditioning memory traces. An area of recent research interest concerns extinction, the process in which a conditioned fear response is gradually lost if the conditioned stimulus is repeatedly presented without adverse consequences. It is now clear that extinction is not a passive process, but depends 
on interactions between amygdala and the cingulate cortex.
(31)

(31)
This circuit has been implicated in depression and anxiety in humans, in which dysphoric mood and affect are abnormally maintained, i.e. not extinguished.
(32)
Despite at least 20 years of cognitive science research in implicit memory, procedural memory, or habit formation, there are no commercially available versions of these tests. In part, this may have to do with lack of psychometric evaluation of test-retest reliability, ceiling or ﬂ  oor effects, etc. or unclear relations to functional status

or outcome. It might be possible to adapt some instrumentation used experimentally (e.g. rotor pursuit) if there are adequate local normative data for the test. There are several forms of implicit learning, all of which are thought to involve learning or memory without conscious awareness of recall. Various motor skills can be learned incrementally, such as rotor pursuit or mirror tracing. Others involve motor sequences. Probabilistic learning can occur when there is acquisition of information or representations that reﬂ ect underlying structural regularities in the input, i.e. when 
there are statistical regularities between stimuli and responses.
(33)
This can occur in tasks as seemingly disparate as the so-called weather prediction task (characterized by probabilistic relation-ships between speciﬁ  c stimulus conﬁ  gurations and a response, in 
this case ‘sunshine’ or ‘rain’) and artiﬁ  cial grammar. Critically,

this case ‘sunshine’ or ‘rain’) and artiﬁ  cial grammar. Critically, 
implicit learning can occur even when the episodic system of recol-lection is dysfunctional.
Other types of implicit memory may be item speciﬁ  c, including 
some types of priming. Priming is thought to be an instance of memory without awareness. Such priming can be reﬂ  ected in 
improvements in accuracy or reaction time during testing. It can be demonstrated in a variety of tasks, some rather rareﬁ  ed, like 
word stem completion, and some rather simple and robust, like so-called repetition priming. In the latter paradigm, an item is repeated 
and access to it (usually measured in reaction time) is speeded
at the second presentation, while concomitantly, physiological measures, ranging from single cell activity to BOLD activation, demonstrate reductions in neocortical areas (e.g. for words, inferior prefrontal cortex). Some of these effects may be quite long, lived.

The degree to which episodic memory may also support some 
types of priming is sometimes unclear and may depend on the para-digm and experimental manipulations. Perhaps the best evidence that priming reﬂ  ects a dissociable memory system comes from 
amnesic patients in whom there is little chance that the episodic sys-tem is supporting priming (e.g. studies of priming in the amnesic patient HM 
(34)). Additionally, an important and critical review(35)
has proposed that some priming may not reﬂ  ect changes in the 
abstract representation of an item, but rather response learning.
Finally, conditioning (especially classical or Pavlovian) has also 
been considered a type of implicit learning. The neurobiological lit-erature on this phenomenon is quite extensive.
(36) The phenomenon 
itself might be relevant for understanding a wide range of behaviors, including anxiety (as a result of fear conditioning) and preferences.
(c) Working memory
(i) Neural systems

A large body of work has established the importance of dorsolat-eral prefrontal cortex (DLPFC) for working memory. Both the

255
simple maintenance of information over a delay and the manipula-
tion of that information require DLPFC function. In the inﬂ  uential 
model of Baddeley, a ‘central executive’ component of working memory works together with modality-speciﬁ  c storage systems, 
the ‘visuospatial scratchpad’ for visual information and the ‘pho-nological loop’ for auditory information.
(37) While the details of 
how this cognitive account reﬂ  ects neural organization are being 
debated, it is clear from a multitude of studies that DLPFC activa-tion is usually observed in conjunction with activity of posterior cortical areas that receive input from a variety of specialized sen-sory cortices.
(38) Chief among those is the inferior parietal lobule, a

(38) Chief among those is the inferior parietal lobule, a 
brain region strongly and bidirectionally connected with DLPFC that is likely to be important for item storage during working memory. Within DLPFC proper, some models propose a regional differentiation based on the modality of information stored (with more dorsal activation associated with visual, ventral with seman-tic items), while others propose a specialization based on cognitive operations (manipulation of memory items being performed more dorsally than pure maintenance). Clinically, large lesions of DLPFC are invariably associated with working memory impairment, how-ever, problems of similar magnitude are also observed in schizophre-nia, where only subtle structural abnormalities are found in this (as in any other) brain region.
(39) The asso ciation of working memory

(39) The asso ciation of working memory 
impairment with schizophrenia has driven an extensive programme of research aimed at understanding mechanisms underlying memo-ry impairments in this disorder. One well-validated ﬁ  nding from this 
work is the importance of the neurotransmitter, dopamine, for DLPFC function, which has been found to exhibit an ‘inverted u’ shaped relationship with working-memory related activation of DLPFC neurones and dopaminergic, especially D1-receptor, stimula-tion.
(40) It is believed that dopamin ergic tone is essential for optimiz-

ing signal to noise ratio, or tuning, in DLPFC, an essential network property for working memory maintenance. This is further support-ed by a modulation of working memory by a functional variant in the COMT gene which alters the protein’s thermolability and hence its ability to degrade dopamine in cortex, the impact of dextroam-phetamine on N Back driven BOLD activation in fMRI, and the COMT inhibitor tolcapone’s impact on N Back RT.
(41–43)
Interactions between DLPFC and hippocampus may also be 
disturbed in schizophrenia and reﬂ  ect an inability to disengage 
episodic memory processes during working memory.(44)
(ii) Assessment and neuropsychology

The classic test of simple working memory is digit span, which involves repetition of short sequences of digits. Span is assessed by increasing the length of the sequence that can be recalled. Nonverbal working memory often involves short sequences of locations (as in Visual Span in the WMS-R and the so-called Corsi blocks.) T ests thought to depend on simultaneous storage and manipulation of information are generally considered executive in nature. The Letter-Number Span is a good example of this class of tests. In it, the subject is asked to order a short random sequence of letters or numbers numerically and alphabetically. Interestingly, the test is highly correlated with a nonverbal, formally dissimilar, problem solving task, the Wisconsin Card Sort, providing evidence that both these tests engage executive processes. The Card Sort itself may be the best known executive test administered in clinical test batteries. It calls upon such executive abilities as abstraction, set

these tests engage executive processes. The Card Sort itself may be the best known executive test administered in clinical test batteries. It calls upon such executive abilities as abstraction, set shifting, and

response to examiner feedback.An exceptionally well validated computerized battery of ‘frontal 
lobe tests’ called the CANTAB is based on the comparative and pharmacologic challenge literature, as well as human lesion studies. All tests are nonverbal and may involve problem solving (as in T ower of London), various levels of set shifting (in the ID/ED task), and self-ordered pointing that demands that the subject remember his/her own actions.
A widely used test of cognitive control is the Stroop, for which there 
are several commercially available versions. In the critical interference condition, the subject must respond to words printed in incongruent colors (e.g. red) by naming the colour of the ink and simultaneously suppressing the prepotent response to read the word.
There are many experimental tests of working memory and

There are many experimental tests of working memory and 
executive that could in theory be adapted for clinical purposes provided these have adequate local normative data and adequate validity and psychometric characteristics. In general, many of the paradigms that have interested cognitive neuroscientists have not yet become part of routine clinical assessment.
The working memory (WM) system is thought to be a limited 
capacity system that holds information on line when the stimulus is no longer present (perhaps up to 40 seconds, as demonstrated in densely amnesic patients). The idea that WM is a capacity limited system comes from the work of G. Miller.
(2) Several compelling 
accounts now suggest that it may under some circumstance be smaller than Miller’s canonical ‘7±2.’ For instance, in studies of visual stimuli, Luck et al .
(45) have suggested that a visual store

(45) have suggested that a visual store 
may hold only four items. Subsystems include a slave system for short term memory of phonological information. This system includes an articulatory rehearsal mechanism and a phonological store. A visual spatial scratchpad processes visual, non-linguistic infor-mation. An episodic memory buffer is thought to play a role in the interface between working and episodic memory. A central execu-tive is involved in the allocation of cognitive resources during dual tasks and in the manipulation or transformation of information. The central executive may be involved in cognitive control, such that when there is response conﬂ  ict (e.g. during response selection 
in the Stroop task or Eriksen ﬂ  anker task) more resources can be 
made available for biasing decisions.
(46) More speciﬁ  cally, in this

(46) More speciﬁ  cally, in this 
account, cognitive conﬂ  ict is detected (by the anterior cingulate)

account, cognitive conﬂ  ict is detected (by the anterior cingulate) 
and signals are sent to executive areas (in DLPFC) that increase processing resources. The increase in resources is used to bias a response to one or another aspect of the stimulus’ features. Importantly, various computational models of this process have shown that a homunculus (i.e. a director or decider) is not neces-sary for a correct response to be made. There is ongoing interest in how best to characterize operations in the WM system. One view that posits a single algorithm that maintains a stable representation over a delay (although subsystems may be dedicated to spatial, object or verbal information) can be used to characterize the basic function of this system. Goldman Rakic and colleagues provided much neu-robiological evidence in favor of this argument. Another view holds 
that multiple computational algorithms perform a variety of

that multiple computational algorithms perform a variety of 
tasks.
(47,48)  Such functions as attentional set shifting, planning, and 
monitoring of sequences of responses (self or externally generated) can be brought to bear on a task, depending on its demands and are separable from basic mnemonic maintenance functions.
Updating of information in WM (i.e. registering information 
and dumping information from a buffer) and suppression of inter-2.5.3 psychology and biology of memory

SECTION 2  the scientific basis of psychiatric aetiology 256
ference may also engage the executive system and may be critical 
for reﬁ  ning goal-directed behavior.(49) In one version of a task that 
makes continual demands for updating and resistance to interfer-ence, a restricted set of numbers are displayed successively (and approximately every two seconds) and the subject views one while responding by pressing a button corresponding to a stimulus ‘one back’ . Thus, the subject must continuously update his/her working memory buffer in that a target-to-be must be shifted in status to a target prior to being ‘dumped’ from a computational buffer and interference from other similar stimuli must be sup-pressed. Recent data (see below) suggest that dopaminergic tone at the cortical level may be particularly important in this speciﬁ  c 
aspect of cognitive control.
Finally, there are several integrative accounts of goal directed

Finally, there are several integrative accounts of goal directed 
behaviour that are dependent on various working and executive functions. In perhaps the best known of these, a ‘script’ that engages multiple short-term and long-term memories bridges the temporal gap for projects that may be quite long temporally.
(50)
Future directions
As our understanding of neural systems involved in memory dysfunction in a variety of psychiatric disorders matures, it will be important to leverage that knowledge to identify new molecular treatment targets. One important recent development in this direction is the identiﬁ  cation of genes impacting on memory 
function. Genetic variation in the neurotrophic factor BDNF, for example, has been shown to impact on hippocampal function and episodic memory,
(51) as have several risk genes for schizophrenia.(52)

COMT, a gene that impacts on cortical dopamine concentrations, affects working memory performance and prefrontal activa-tion.
(41, 53)  Risk genes for depression and anxiety may affect amyg-
dala-cingulate and amygdala-hippocampal interactions that are important for fear extinction and emotional memory, respectively, providing neural mechanisms for gene by environment interac-tions mediating the effects of early adverse experience on riskfor psychiatric disorders.
(32, 54)  Translational strategies for drug 
development can arise from these ﬁ  ndings. The COMT inhibitor 
tolcapone has been shown to improve working memory in nor-mals.
(43) Data suggesting an impact of stress hormones such as

(43) Data suggesting an impact of stress hormones such as 
corticosteroids on hippocampal integrity in posttraumatic stress disorder suggest neuroprotective strategies to prevent development of disease before anticipated exposure, for example in battle. Finally, it has become clear that memory impairment is an important pre-dictor for treatment response in psychiatry, schizophrenia being an important example, and neurorehabilitative programs to improve memory are being explored. The study of the neurobiology of memory is therefore a promising avenue towards improved and speciﬁ  c therapies in psychiatry.
Miyake, A. and Shah, P . (eds.) (1999) Models of Working Memory: 
Mechanisms of Active Maintenance and Executive Control .
Cambridge University Press, New Y ork.
Squire, L.R. and Schachter, D.L. (eds.) (2002), Neuropsychology of Memory .

The Guildford Press, New Y ork.
Hippocampus  (the journal).
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2.5.4 The anatomy of 
human emotion
R. J. Dolan

R. J. Dolan
Emotions, uniquely among mental states, are characterized by psy-
chological and somatic referents. The former embody the subjec-tivity of all psychological states. The latter are evident in objectively measurable stereotyped behavioural patterns of facial expression, comportment, and states of autonomic arousal. These include unique patterns of response associated with discrete emotional states, as for example seen in the primary emotions of fear, anger, or disgust often thought of as emotion proper. Emotional states are also unique among psychological states in exerting global effects on virtually all aspects of cognition including attention, percep-tion, and memory. Emotion also exerts biasing inﬂ  uences on high 
level cognition including the decision-making processes that guide extended behaviour. An informed neurobiological account of emotion needs to incorporate how these wide ranging effects are 
mediated.

mediated.
Although much of what we can infer about emotional processing 
in the human brain is derived from clinic-pathological correla-tions, the advent of high resolution, non-invasive functional neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) has 2.5.4 the anatomy of human emotion

SECTION 2  the scientific basis of psychiatric aetiology 258
greatly expanded this knowledge base. This is particularly the case 
for emotion, as opposed to other areas of cognition, where norma-tive studies have provided a much richer account of the underlying neurobiology than that available on the basis of observations from pathology as in classical neuropsychology.
Emotion has historically been considered to reﬂ  ect the product 
of activity within the limbic system of the brain. The general utility of the concept of a limbic-based emotional system is limited by a lack of a consensus as to its precise anatomical extent and bound-aries, coupled with knowledge that emotion-related brain activity is, to a considerable degree, conﬁ  gured by behavioural context.

What this means is that brain regions engaged by, for example, an emotion of fear associated with seeing a snake can have both distinct and common features with an emotion of fear associated with a fearful recollection. Consequently, within this framework emotional states are not unique to any single brain region but are expressed in widespread patterns of brain activity, including activity within early sensory cortices, shaped by the emotion elicit-ing context. This perspective emphasizes a global propagation of emotional signals as opposed to a perspective of circumscribed limbic-mediated emotion-related activity.
The amygdala and emotion
The above considerations aside, the structure most closely afﬁ  liated 
with emotional processing is the amygdala. This structure is an anatomically and functionally heterogeneous, bilateral, collection of nuclei located in anterior medial temporal cortex. The impor-tance of the amygdala in emotional control was ﬁ  rst highlighted by

reports that rhesus monkeys with bilateral temporal lobe ablations no longer show appropriate fear or anger responses.
(1) The role 
of the amygdala in emotion has been subsequently extended by ﬁ ndings that humans with lesions to this structure have impaired 
emotional recognition, particularly for fear, and no longer acquire Pavlovian conditioned responses
(2) (see below). Finally, functional 
neuroimaging ﬁ  ndings show activation of amygdala in responses 
to face stimuli that depict a range of emotions, particularly fear but also other primary emotions.
(3, 4)
The importance of the amygdala in emotion derives in part from 
its extensive anatomical connections with all sensory processing cortices, as well as hippocampus, basal ganglia, cingulate cortex and the homeostatic regulatory regions of hypothalamus and brain stem.
(5) This widespread anatomical connectivity means that this

(5) This widespread anatomical connectivity means that this 
structure can access information processing in multiple brain regions and, in turn, can exert diffuse modulatory inﬂ  uences, 
including inﬂ  uences on effector autonomic and motor output sys-
tems. In this way activation of the amygdala by a sensory based emotional stimulus inﬂ  uences widespread brain regions including 
those that mediate homeostatic regulatory responses as expressed in altered autonomic state, such as change in heart rate, blood pres-sure and respiration.
Learning predictive emotional responses
A central role for emotion is to index value, speciﬁ  cally whether

A central role for emotion is to index value, speciﬁ  cally whether 
present or future sensory events or states of the environment that are likely to be associated with reward or punishment. From this perspective, all emotions are to a greater or lesser degree valanced. For example, an emotion of joy signals a likelihood of reward while an emotion of fear signals a likelihood of punishment. The fact that signals that predict such emotional occurrences are to some degree 
arbitrary means that the brain must have some means of associat-ing sensory cues with potential emotional outcomes, an ability that seems crucial for adaptive behaviour.
Associative learning provides a phylogenetically highly conserved

Associative learning provides a phylogenetically highly conserved 
means to predict future events of value, such as the likelihood of food or danger, on the basis of predictive sensory cues. The amygdala plays a crucial role in mediating this form of emotional learning as evidenced by deﬁ  cits seen with animal lesion data and 
learning-related effects seen in human functional neuroimaging experiments.
(6, 7) In its simplest form, Pavlovian conditioning is 
expressed when a previously neutral sensory stimulus (the condi-tioned stimulus, or CS +) acquires emotional predictive signiﬁ  cance 
through pairing with a biologically salient reinforcer (the uncondi-tioned stimulus, or UCS). With conditioning, the predictive stimu-lus (CS +) comes to elicit behaviour previously associated with the

UCS, but in the absence of UCS presentation. There is a wealth of animal and human data which now shows that the amygdala has a key role in this form of associative learning, for both appetitive and aversive outcomes.
How the brain updates predictions of 
emotional outcomes
While contingencies acquired on the basis of associative learning 
provide a basis for generation of predictions of future event of value in response to sensory cues, this form of learning lacks ﬂ  exi-

bility in optimizing future behaviour. For example, the value of future states associated with predictive cues may change in the absence of subsequent pairing with these cues. Thus, a cue that is associated with a particular food that is valued when a person is hungry has diminished relevance when the person is sated with that same food. Consequently, it is important for optimal adaptive behaviour to be able to maintain an updated representation of the current value of such sensory-predictive cues that does not slav-ishly depend on new learning in relation to that cue.
Reinforcer devaluation is a standard experimental methodology 
for examining how value representations accessed by predictive 
cues are updated. As indicated, in the case of food, its value can be 
decreased through what is termed sensory-speciﬁ  c satiety. In this

decreased through what is termed sensory-speciﬁ  c satiety. In this 
type of manipulation, the reward value of a food eaten to satiety is reduced (devalued) relative to foods that are not eaten to satiety. In humans, functional neuroimaging measured brain responses elicited by predictive stimuli (such as a CS +), that have been subject 
to devaluation, are associated with signiﬁ  cant response decrements 
in the OFC paralleling the behavioural effects of satiation.
(8) This 
response pattern within OFC indicates that this region is involved in representing reward value of predictive stimuli in a ﬂ  exible man-
ner, observations that also accord with extensive evidence from animal lesion data.
(9, 10)
The observation that neural responses evoked by a food predictive 
conditioned stimulus (a CS +) in OFC are directly modulated by

(9, 10)
conditioned stimulus (a CS +) in OFC are directly modulated by 
hunger states can inform an understanding of the behavioural impact of pathologies that impact on orbital-frontal cortex, especially the feeding abnormalities observed in both the Kluver-Bucy syndrome and fronto-temporal dementias. Patients with these conditions frequently show increased appetite, indiscriminate eating, food cramming, and change in food preference, hyperorality, and even attempts to eat non-food items. A dysfunctional network

259
involving OFC and amygdala would mean that food cues, and 
other predictive cues, are unable to recruit motivationally appro-priate representations of food-based reward value.
A computational account of emotional learning
Learning to predict reward or danger is a basic and highly con-served form of learning, as embodied in Pavlovian or associative learning. However, to be maximally adaptive, it is important that this form of learning is used not only to predict but also to shape optimal actions. The computational principles that underpin what is now referred to as value learning, involving prediction and opti-mization of action with respect to likely future outcomes, is more than an abstract issue and speaks to the critical issue of optimal control in decision-making.
One classical solution as to how associative learning is imple-

mented is by means of a signal, referred to as a prediction error, which registers a difference between a predicted and actual outcome. This type of solution to predictive learning has been formalized within what is known as the Rescorla-Wagner learning rule. T emporal difference learning (TD) provides a more sophisticated 
computational extension of this learning rule that accounts in a 
precise manner for how an organism learns to make predictions, as well as select optimal actions, in response to states of the envi-ronment so as to maximize long-term reward or avoid long-term punishment.
(11) As in the case of the Rescorla-Wagner model, when

(11) As in the case of the Rescorla-Wagner model, when 
a positive (or negative outcome) is not predicted there is a large prediction error which reduces to zero when this same outcome is fully predicted. The function of the prediction error is to act as a teaching signal that can both update future predictions as well as shape optimal policies or action choic es. In temporal difference 
learning (TD), credit is assigned by means of the difference between temporally successive predictions, rather than between a predictive stimulus and an outcome, such that learning occurs whenever there is a change in prediction over time.
The importance of the above theoretical considerations rests 
upon empirical observations that TD error-like responses have now been demonstrated in the response pattern of dopamine neurones recorded in monkeys during associative learning.
(12) Consequently,

(12) Consequently, 
in a classical conditioning context where a stimulus is followed by an unexpected reward it can be shown that dopamine neurones respond with a burst of action potentials after actual reward receipt. Over the course of learning, with repeated presentations of a pre-dictive stimulus and reward, dopamine neurones no longer respond to receipt of the reward. In this latter case, the reward is accurately predicted because of the occurrence of the preceding predictive stimulus. What is now observed is a prediction error at the time of the earliest predictor of this reward, for example at time of pres-entation of a predictive CS stimulus. Prediction error type brain responses have also been shown to occur in the human striatum and orbital-prefrontal cortex during both Pavlovian and Instrumental learning in humans, as measured by fMRI.
(13, 14)

(13, 14)
Indeed, a crucial link between a dopamine prediction error signal, human striate activity and reward-related choice behaviour in humans has also been shown using fMRI techniques. In this latter case, a reward outcome prediction error signal was enhanced by boosting the impact of dopamine using L-dopa (a precursor of dopamine), while a dopaminergic blocker Haloperidol led to an attenuation of a prediction error signal. Crucially, the former manipulation was associated with enhanced reward learning while the latter was associated with impaired reward learning in a man-
ner that indicates that a reward outcome prediction error is involved in shaping optimal behaviour.
(15)
How emotion inﬂ  uences memory
The cognitive domain where the modulatory inﬂ  uences of emotion

(15)
The cognitive domain where the modulatory inﬂ  uences of emotion 
have been best characterized is with respect to episodic memory, the type of memory that underpins autobiographical experience. Emotion enhances episodic memory function as seen in an enhancement for material that encompasses personal autobio-graphical, picture, and word based-items, an effect best seen in free recall tasks.
(16) The critical role played by the amygdala in this 
modulation is illustrated by functional neuro imaging experiments where amygdala activity during encoding predicts a beneﬁ  t in later 
recall of emotional material relative to neutral material.
(17) Thus, 
enhanced amygdala activity at encoding for both positive and neg-ative stimuli is predictive of later episodic memory function, dur-ing free recall tasks.
During encoding of emotional items there are bi-directional

During encoding of emotional items there are bi-directional 
interactions between amygdala and hippocampus, the latter struc-ture being a region essential for episodic memory formation. The bi-directional interaction between amygdala and hippocampus is inferred from the fact that an enhanced amygdala response, mea-sured using functional neuroimaging, to presentation of emotional items is dependent on inﬂ  uence from hippocampus. Conversely, an 
enhanced hippocampal response to emotional items is depend ent on inﬂ  uences from the amygdala.
(18) While these studies were car-
ried out at encoding it is important to acknowledge a role for the amygdala during retrieval of emotional items and contexts.
How emotion inﬂ  uences perception
Emotion often signals an environmental event of value. From an

Emotion often signals an environmental event of value. From an 
evolutionary perspective, it is important that such occurrences are amenable to privileged perceptual processing. There appears to be two distinct mechanisms by which emotion can inﬂ  uence percep-
tion of such event. One of these is through emotion grabbing atten-tion, leading to enhanced deployment of attention to an emotional eliciting stimulus. This would result in preferential detection of emotional events enabling appropriate adaptive responses to be enacted.
There is also evidence for a second means by which emotion can 
inﬂ uence perception that appears to operate independent of atten-
tion. For example, in visual backward masking paradigms, a target presented for a brief instance can be rendered invisible if it is immediately followed by a second ‘masking stimulus’ . In situations 
where the hidden target stimulus is an emotional item, for example,

where the hidden target stimulus is an emotional item, for example, 
a conditioned angry face or a spider, there is preserved processing. This is evident in differential skin conductance responses (SCRs) to fear-relevant compared to fear-irrelevant unseen targets.
(19) Similar 
ﬁ ndings are reported using what is referred to as an attentional blink 
paradigm. The latter refers to a situation where detection of an initial target stimulus, in a stimulus stream, leads to impaired awareness, or inattentional blindness, for a successive second tar-get. Critically, when this second target has emotional content there is an increased probability of its detection as opposed to the default attentional blindness.
(20)
In terms of anatomical substrates of these modulatory effects, 
there is compelling evidence to implicate the amygdala.  In functi onal 2.5.4 the anatomy of human emotion

SECTION 2  the scientific basis of psychiatric aetiology 260
neuroimaging experiments, using visual backward masking para-
digms, an amygdala response discriminates between unseen emo-tional and unseen non-emotional target.
(19) In other experiments 
that involve overt stimulus presentation, but where attention is sys-
tematically manipulated, such that emotional items are presented out of the window of attention, an amygdala response to emotional stimuli is independent of the concurrent attentional focus.
(21)
Likewise, in studies of patients with either blindsight (loss of primary visual cortex resulting in visual ﬁ  eld blindness) or visual 
extinction (a situation following a lesion to the right inferior pari-etal cortex whereby subjects cannot consciously represent stimuli in the contra-lesional visual field) demonstrate an amygdala response to emotional stimuli presented out of awareness in the damaged hemiﬁ  eld.
(22)

(22)
How pre-attentive processing of emotional events inﬂ  uence, and 
enhance, perception is an important mechanistic question. One possibility is that inputs from emotional processing regions, in par-ticular the amygdala, modulate the very regions involved in object perceptual processing, speciﬁ  cally when this relates to an emotion

eliciting object or event. Anatomically, the amygdala receives visual inputs from ventral visual pathways and sends feedback projections to all levels of this pathway. Neuroimaging data provide evidence for enhancement of the strength of connectivity between amygdala and extra-striate visual regions during processing of an emotional visual input. In patients with amygdala lesions, the enhancement of activity seen in early extra-striate visual areas during encoding of emotional items, for example faces, is no longer expressed. Crucially, neuropsychological data from patients with amygdala damage indicate that a perceptual enhancement seen in extra-striate visual 
cortex for emotional items is abolished following damage to this 
structure.
(23) This type of evidence is consistent with a proposal 
that boosting of activity in early sensory cortices, when an emotional stimulus is encountered, reﬂ  ects a direct modulatory 
inﬂ uence from the amygdala.

The neurobiology of subjective feeling states
Human emotion research often conflates the neurobiological 
mechanisms that index the perception or occurrence of an emotional event (representational aspects of emotion) with their subjective experiential counterparts, usually referred to as feeling states. Feelings can be formally deﬁ  ned as mental representations 
of physiological changes that characterize, and are consequent upon, processing an emotion eliciting object event or image.
(24)
This deﬁ  nition assigns an important causal role in the genesis of 
subjective feeling states to afferent feedback to the brain from the body, both sensory and neurochemical. At a broader level, feeling states can be thought of as reﬂ  ecting the operation of homeostatic

mechanisms that underlie survival of the organism. In a recent theoretical model, based on neurological observations, prime emphasis is given to the cerebral representation of bodily states as providing the substrate for the conscious awareness of feeling states.
(25)
A key neurobiological question is whether brain systems 
supporting emotional perception are distinct from those support-ing feelings states. Candidate structures that mediate feeling states encompass those involved in bodily homeostasis and that process information regarding the bodies internal milieu including brain stem peri-acqueductal grey (PAG) and parabrachial nuclei, tegmentum, hypothalamus, insula, somatosensory and cingulate 
cortices. Functional neuroimaging provides strong evidence that feeling states are mediated by distinct neuronal systems to those that support emotional perception.
(26) Thus, functional neuroim-
aging studies of volunteer subjects have shown that the central

aging studies of volunteer subjects have shown that the central 
generation and re-representation of peripheral autonomic states involve structures such as anterior cingulate and insular cortex. For example, recall of subjective feeling states associated with past emotional experiences engages regions encompassing the upper brainstem nuclei, hypothalamus, somatosensory, insular and orbi-tofrontal cortices. In subjects with pure autonomic failure (PAF), where there is absence of visceral afferent and information regard-ing the peripheral body state due to selective acquired peripheral 
autonomic damage, there is attenuation of subjective emotional 
feelings as well as emotion evoked neuronal activity in regions implicated in mediating feeling states, such as anterior cingulate and insula cortex.
(27)
Among the regions most strongly implicated in mediating

(27)
Among the regions most strongly implicated in mediating 
subjective feeling states is the insula cortex, an extensive region of cortex enfolded from the cortical surface within temporal lobes. Direct evidence for its role in representing subjective feeling states comes from investigations that tap awareness of internal bodily states, such as that required in performing a heartbeat detection task.
(28) In this task, subjects who have the ability to detect and 
accurately report their own heartbeat, which is seen as evidence of somatic awareness, show enhanced activity in the anterior insula cortex when performing such a task.
(29)
The proposal that the insula cortex area mediates subjective 
feeling states is bolstered by evidence that empathetic awareness of the subjective feeling states of others, for example, that engendered when one observes another person receiving pain, is reﬂ  ected 
in enhanced activity within anterior insula and cingulated cor-tex.

(30) These same regions are also engaged when a subject is 
exposed to a pain eliciting stimulus suggesting the same neural matrix that represents subjective feeling states is engaged when representing the subjective feeling states of another person.
(a) Imaging emotional inﬂ  uences on decision-making
Emotion is frequently invoked as inﬂ  uencing decision-making, 
often detrimentally, a view that tends to pit a hot ‘irrational’ emotional decision system in opposition to a cold ‘rational’ cogni-tive decision-making system. This dichotomy almost certainly represents a simpliﬁ  cation and there are compelling neurobiologi-
cal reasons to suggest multiple decision-making systems in the human brain with emotion in many instances facilitating optimal decision-making.
Real-life decision-making often involves choices between actions

Real-life decision-making often involves choices between actions 
which yield potential rewards or punishments, albeit with some element of uncertainty, for example, as manifest in varying proba-bilities and magnitudes of outcomes. Adaptive decisions that seek to optimize goal-oriented behaviour require an estimation of expect-ed future reward that will follow from choosing a particular action. 
This behaviour can be described as utility maximization. As out-
lined previously, reward prediction based on expected reward value can be studied through classical conditioning, in which an arbi-trary cue (or conditioned stimulus) takes on predictive value by association with subsequent delivery of an affectively signiﬁ  cant 
or unconditioned stimulus (which can be a reward or punishment, or strictly speaking, an appetitive or aversive stimulus).

261
Neuroimaging studies implicate OFC alongside structures such 
as amygdala and ventral striatum in prediction for reward and punishment.
(31) As described above, human neuroimaging studies 
of classical conditioning for reward have highlighted a prediction 
error signal in prominent target areas of dopamine neurones, including the striatum and OFC. The ﬁ  nding that a neural reward 
prediction error signal is expressed, present in OFC and striatum, and indeed throughout the reward network, is consistent with the idea that this signal provides a basis for ﬂ  exible learning and updat-
ing of stimulus-reward associations.
(33)
Accounts of human decision-making emphasize rationalistic

(33)
Accounts of human decision-making emphasize rationalistic 
perspectives which invoke analytic processes mediated by an execu-tive prefrontal cortex. An emotional or value based contribution to high level decision-making is evident following ventromedial pre-frontal cortex damage where, despite the absence of intellectual deﬁ cits, such patients often make real life decisions that are disad-
vantageous.
(33) The types of deﬁ  cits seen in these patients have

(33) The types of deﬁ  cits seen in these patients have 
been conceptualized as a myopia for the future, in which current needs (as opposed to an integration of current and future needs) dominate decision-making. Observations from patients with this type of lesion has led to the suggestion that this ventromedial OFC provides access to feeling states evoked by past decisions during contemplation of future decisions of a similar nature. Thus, evoca-tion of past feeling states biases the decision-making process, towards or away from a particular behavioural option.
(34) However, 
alternative frameworks that might explain behavioural deﬁ  cits seen 
following damage to this region include an inability to represent the value of competing options for action or extreme discounting of future rewards (a myopia for the future), leading to an overvalu-ing of current as opposed to future rewards.
It is well recognized that normative human decision-making

It is well recognized that normative human decision-making 
does not always accord with rationalistic perspectives of utility maximization. An inﬂ  uence of prior emotional experience on deci-
sion processes is captured by the consequences of an emotion such as regret. Regret is an emotion generated by counter-factual think-ing involved in comparing an obtained and foregone outcome which indicates to the subject that the latter, if chosen, would have been more advantageous. In this sense, regret is also a prototypical example of a secondary or higher order emotion, meaning that it 
emerges out of cognitive or higher order processing as opposed to

emerges out of cognitive or higher order processing as opposed to 
being stimulus elicited as in the case of fear or disgust (prototypical exemplars of primary emotions). It is known that subjects who experience regret as a consequence of a choice show a subsequent bias away from a rationalistic imperative that invokes a maximiza-tion of expected value when making similar choices, an effect that can be explained as regret minimization. This behavioural bias is associated with engagement of the amygdala and orbitofrontal cortices regions, that are also engaged by the actual experience of regret.
(35) This pattern of brain response is consistent with 
theories that suggest evocation of past emotions in the context of decision-making, providing a biasing inﬂ  uence on rational 
decision processes.
An additional tenet of rational behaviour is the idea that human

An additional tenet of rational behaviour is the idea that human 
decisions should be consistent regardless of how choices are pre-sented. One notable deviation from this axiom is described as a framing effect. In simple terms, the framing effect describes a bias in decision-making observed when choices are presented in terms of gain, leading to choices of a sure as opposed to a risky option, versus the same choices presented in a loss where subjects are biased to choose a risky option. Functional neuroimaging data show that 
a framing engendered bias in human decision-making, risk aver-siveness in the gain and risk seeking in the loss frame, is associated with enhanced amygdala activity at the point of decision-making.
(36) The suggestion here is that an emotional heuristic, 
mediated via key emotion processing brain regions, is invoked when humans make decisions under situations where information is incomplete or overly complex.

The neurobiology of human emotion has now undergone a radical revision with the development of sophisticated neuroimaging technologies. There is a clear evidence that it no longer makes sense to think of the brain in terms of simple dichotomies such as limbic and non-limbic. Emotion engages widespread regions of the brain with the precise regions being dynamically con
ﬁ gured as a function 
of behavioural context. Thus, patterns of brain activity evoked by the seeing a fear eliciting stimulus, such as a snake, are distinct from those evoked when seeing another person in pain. The former situations involve activation of the amygdala and through its modulatory effects it inﬂ  uences widespread interconnected regions,

including early sensory cortices. The latter situation results in engagement of distinct structures such as the insula and cingulate cortex. Learning about likely emotional occurrences involves a distinct teaching signal, a prediction error, expressed in widespread brain regions including the striatum and OFC, the latter region mediating a ﬂ  exible representation of the value of emotional occur-
rences including reward.
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2.5.5 Neuropsychological 
basis of neuropsychiatry
Neuropsychology makes an essential contribution to neuropsychi-

atry. It seeks objectively to characterize mental competence in com-ponent cognitive functions such as perception, attention, spatial cognition, memory, learning, language, thinking, and ‘executive’ function. Executive function is often associated with the functions of the frontal lobes, although these are not at all synonymous; we will pay special attention to this domain below, as it may be crucial to the understanding of several neuropsychiatric disorders. Neuropsychology is often conveniently divided into clinical neuro-psychology and cognitive neuropsychology. The former is primar-ily concerned with the methodology and psychometric theory that lies behind the selection, administration, and interpretation of standardized psychological tests aimed at assessing deviation from the norm and an individual patient’s proﬁ  le of strengths and weak-

nesses with a view to optimizing functional outcome and quality 
of life. Cognitive neuropsychology, by contrast is more concerned with the elucidation of cognitive processes through the study of patients, using both classical and newly devised tasks.
(1)
Neuropsychology also forms part of cognitive neuroscience, which has as its major goal the understanding of normal, as well as abnormal cognitive function, not only through the neuropsycho-logical study of patients and healthy controls, but also using other techniques, including functional neuroimaging and the use of tran-scranial magnetic stimulation or psychopharmacology. In practical

263
terms, a neuropsychological assessment is often made together 
with a psychiatric examination; in addition to contributing to diag-nosis it also helps to deﬁ  ne the functional status of the patient .
Functions of neuropsychological assessment
These are perhaps easiest to deﬁ  ne when there has been an organic 
brain injury causing a lesion; for example, due to a stroke, removal of a tumour, or a closed or penetrating head injury. It is clearly vital to have an accurate evaluation of a patient’s cognitive status so that his or her care can be optimized. This applies equally in neuropsy-chiatric disorders. In conditions like attention-deﬁ  cit/hyperactivity 
disorder (ADHD) or prodromal Alzheimer’s disease, the cognitive examination provides essential information for making a diagno-sis. Whilst acquired brain damage can lead to neuropsychiatric symptoms (e.g. depression or apathy), it may also be associated with speciﬁ  c patterns of cognitive deﬁ  cit. However, most neuropsy-

chiatric disorders are not associated with clearly deﬁ  ned brain 
injuries, but are instead hypothesized to result from the cumulative effects of neurodegenerative disease, neurotransmitter malfunc-tions, developmental hypoplasias, diffuse white matter lesions, or brain volume gains and losses. This is an important point, as it may require more sensitive new methodologies to characterize deﬁ  cits 
produced by regional overactivity , or deﬁ  cits associated with changes 
in regional connectivity , as distinct from brain lesions per se. In 
these examples, neuropsychology offers the opportunity to exam-ine underlying pathophysiological mechanisms, in combination with other methods such as structural and functional brain imag-ing and evoked brain potentials.
Cognitive deﬁ  cits (e.g. of memory) can exist in parallel to, and

Cognitive deﬁ  cits (e.g. of memory) can exist in parallel to, and 
independently of, psychiatric symptoms (e.g. of melancholia) but they may also be intrinsic to them. For example, part of the psychi-atric description of anxiety may emphasize abnormal attentional biases paid to threatening stimuli, which can be objectively assessed using cognitive testing.
(2) Furthermore, some psychological factors 
may inﬂ  uence performance across a number of distinct cognitive 
domains, producing a broad proﬁ  le of impairments from a relatively 
speciﬁ  c form of deﬁ  cit. For example, patients with depression may 
show a ‘catastrophic response’ to receiving error feedback during testing, such that they are then more likely to respond incorrectly on the subsequent trial.
(3) This interaction of emotional and social

(3) This interaction of emotional and social 
factors with cognitive processes forms an especially important part of neuropsychology as applied to psychiatry. Neuropsychology also enables the impact of neuropsychiatric symptoms to be assessed on functional status—whether the patient will be able to function in everyday life, and return to paid employment, and how rehabili-tation may be best achieved. It is becoming clear that the effective treatment of certain symptoms (e.g. psychotic symptoms) can sometimes unmask profound cognitive impairments that are actually the main barrier to rehabilitation, as has recently been shown in schizophrenia.
(4,5) Taking into account the corollary 
ﬁ nding that cognitive status may be the best predictor of functional 
outcome and return to paid employment, this has made cognitive disabilities a new target for pharmaceutical treatment. Of course, with schizophrenia again in mind, it is also necessary to ascertain that

medication is not associated with signiﬁ  cant cognitive toxicity, for 
example in terms of sedation, distractibility, or impaired judgement. 
Neuropsychology must play a major role in providing such evi-
dence. Sometimes neuropsychology may substantially contribute to the diagnosis itself of a psychiatric state, for example in 
dissociative disorders and in the study of fatigue disorders and malingering.
Principles of neuropsychological testing
Neuropsychological scores on most tests are standardized with respect to overall age, IQ, and ideally gender. Parallel forms of tests exist in different languages although cultural and ethnic factors are still difﬁ  cult to take account of adequately. T esting is generally done

in a quiet room without distraction by an experienced clinical neuropsychologist. Most tests have generally been shown to give consistent results when given by different testers and on different occasions to the same patient, when using standardized instruc-tions. These ‘inter-tester’ and ‘test–retest’ forms of reliability are often critical factors in situations where testing has to be repeated, for example, in drug trials, or epidemiological studies.
(6) Good 
test–retest reliability (i.e . r > 0.8) can be hindered by practice 
effects that markedly change how subjects approach the tasks. Such factors typically affect measures of executive function, where the subject may evolve strategies for dealing with the task over repeated test sessions. The various cognitive domains are usually tested in one or two sessions that contain an assortment of tests drawn from the types described above to provide a cognitive proﬁ  le of the

patient. The duration of the test sessions should be carefully considered in view of the concentration span and distractibility, or apathy of many patients. Neuropsychological test batteries normally comprise a selection of paper and pencil tests which are being supplemented increasingly with computerized elements. Computerized tasks beneﬁ  t from the ease and accuracy of record-
ing and analysing complex data (e.g. reaction times), and of stan-dardizing the presentation of the test materials and trial-by-trial

ing and analysing complex data (e.g. reaction times), and of stan-dardizing the presentation of the test materials and trial-by-trial 
feedback. The Cambridge Neuropsychological T est Automated Battery (CANTAB), for example, utilizes a touch sensitive screen that allows the subject to interact directly with the test materials and obviates the need for divided attention between a video moni-tor screen and keyboard or desktop. Other possible advantages of computerized testing include the removal of the ‘confrontational’ or ‘interrogative’ elements of conventional testing, which may be especially advantageous when testing, for example, schizophrenic patients. The construction of batteries may also be affected by other factors such as the need to translate ﬁ  ndings, presumably through

the use of non-verbal tests, across species, based on the extensive knowledge of underlying neurobiological mechanisms gained through studies of non-human primates. Alternatively, there is a trend to customize neuropsychological batteries so as to focus on typical deﬁ  cits in a given disorder, as illustrated by the recent 
derivation of the MATRICS battery for cognitive deficits in schizophrenia.
(7)
Domains and neuropsychological tests 
of cognitive function
Neuropsychological assessment is made generally with respect to 
the overall proﬁ  le of cognitive performance. For example, it is 
difﬁ cult to interpret an apparent memory deﬁ  cit if the subject has 
a profound impairment in perception or attention. An important index of overall performance is the intelligence quotient, or IQ. The structure of intelligence is still being debated; whether there is a distinction for example between Cattell’s ﬂ  uid and concrete 2.5.5 neuropsychological basis of neuropsychiatry

SECTION 2  the scientific basis of psychiatric aetiology 264
intelligence, and the possible existence of a general factor, 
Spearman’s g versus Thurstone’s more speciﬁ  c components.(8)
Regardless of these theoretical issues, it is still useful to classify an

Regardless of these theoretical issues, it is still useful to classify an 
individual in terms of their overall intelligence with a mean scaled score of 100 and a standard deviation of 15. IQ is often measured using sub-tests from the Wechsler Adult Intelligence Scale (or the child equivalent, the WISC), which broadly subdivides into verbal and non-verbal (‘performance’) components. The individual sub-tests include such categories as vocabulary, information, compre-hension, arithmetic, digit span, similarities, block design, picture arrangement, picture completion, object assembly, and digit sym-bol, which thus probe a range of abilities from general knowledge and basic language skills to memory span, working memory, visuo-spatial construction, and psychomotor speed. As the time taken to make all these assessments can be prohibitive, a ‘prorated’ score based on a smaller selection of the tests is often employed, justiﬁ  ed

by the relatively high inter-correlation of performance among the 12 sub-tests. Intelligence is also measured effectively by the Raven’s Matrices, a set of visuo-spatial problems based on analogies.
Frequently, it is useful to be able to gauge the patient’s premorbid 
intelligence level, before the onset of psychiatric symptoms. One way of estimating this is from years of education, as frequently employed in the United States. A second method depends on the National Adult Reading T est (NART), an instrument that depends on the subject’s ability to pronounce infrequent words; this corre-lates with educational level, and its utility was realized when it 
became apparent that patients with Alzheimer’s disease showed 
relative sparing of reading abilities, thus enabling their premorbid IQ to be captured by this test.
(9) Alongside its US analogue, the

(9) Alongside its US analogue, the 
Wechsler T est of Adult Reading (WTAR), the NART is now widely used to estimate premorbid intelligence in neuropsychiatric disorders including schizophrenia.
Superimposed on this general assessment of IQ is performance 
on tests of more speciﬁ  c abilities. The Wechsler Memory scale

on tests of more speciﬁ  c abilities. The Wechsler Memory scale 
provides a method by which memory can be assessed in the context of overall intelligence. Some of its components, such as the Logical Memory test are still much used. However, with our burgeoning theoretical understanding of the components of cognition has come the introduction of ever more sophisticated instruments for measuring sub-components of cognitive performance. This brief chapter can but summarize some of the consequences of this, and encyclopaedic compilations of the various tests are now avail-able, together with details of their mode of administration and 
interpretation.
(10) However, the main domains of function that are 
generally evaluated are now outlined.
Over and above basic clinical sensory testing, measures of higher

Over and above basic clinical sensory testing, measures of higher 
order perception in either the auditory or the visual modalities are available—for example, the Visual Object and Space Perception Battery.
(11) Memory function is a controversial and complicated 
area of assessment. Most rapid batteries include tests of recogni-tion memory, simply deciding whether or not a stimulus is familiar or not. Recent evidence, for example from the animal literature, suggests that such memory is relatively independent of hippocam-
pal function, and depends instead on such regions as the perirhinal 
cortex.
(12) Verbal recall, particularly a free recall, is considered to be

cortex.
(12) Verbal recall, particularly a free recall, is considered to be 
a more demanding form of memory, thought to require the coor-dinated functioning of medial temporal lobe and frontal lobe struc-tures. The frontal lobes are also implicated in retrieval of the temporal sequence or order of events, or the source of a particular 
memory in the past. Tulving’s distinction between episodic and semantic memory is still inﬂ  uential.
(13) Episodic memory generally 
refers to the subjective reminiscence of an event that has ‘what, where, and when’ qualities, almost invariably associated with a per-son’s autobiographical memory. By contrast, semantic memory reﬂ ects memory for facts that may well have a different form of 
representation within the temporal lobe and is importantly inﬂ  u-

enced by verbal processes. In addition to these various modalities of memory material, are speciﬁ  c memory processes that have to be 
evaluated, such as encoding and retrieval. The latter is often assessed efﬁ ciently by the so-called verbal ﬂ  uency tests, in which subjects 
have to retrieve words from a semantic category (e.g. animals) or beginning with a speciﬁ  c letter (e.g. F) in a set time period, usually

have to retrieve words from a semantic category (e.g. animals) or beginning with a speciﬁ  c letter (e.g. F) in a set time period, usually 
of 60 s. Standardized tests of learning of verbal or non-verbal forms of material are provided by the California Verbal Learning T est (CVLT), the Rey Auditory Verbal Learning T est (RAVLT), and the CANTAB Paired Associate Learning (PAL) test. Emotional memory, which almost certainly implicates such structures as the amygdala, is another area of memory research that requires urgent develop-ment for application to psychiatry, for such conditions as Post-Traumatic Stress Disorder (PTSD). However, it is difﬁ  cult to see 
how the current tests of traditional neuropsychology can be of much assistance here when the problem is to quantify the disrup-tive effect of a speciﬁ  c memory that has become over-salient rather 
than inaccessible.
Working memory is another important component of memory

Working memory is another important component of memory 
that refers to the coordination of various short-term memory stores to provide more permanent representations and aid in the solution of ongoing activities such as planning and discourse. Working memory comprises short-term visuo-spatial and verbal memory stores, with postulated rehearsal processes (e.g. the articu-latory ‘loop’) and a ‘central executive’ system. Perhaps a simple way of understanding what working memory accomplishes is to contrast digit span in a forward and backward modes (e.g. repeat back the sequence ‘5 2 3 7 1’ in either the same order, or in the reverse order). In the former case, it represents the buffer capacity of the verbal store, whereas in the latter case, the response sequence requires manipulation at output. Working memory reﬂ  ects the

active (‘conscious’) processing of memory traces whether at the encoding or retrieval stages and is clearly dependent on such factors as attention and arousal level.
Attention is a complex theoretical construct that has gained 
much in recent years from its analysis in terms of underlying neural systems.
(14) Unfortunately, despite the interest in attention 
from experimental psychology, there are not many standardized tests of attention in general use. A common distinction is between the automatic forms of ‘covert’ attention mediated by posterior cortical structures and voluntary forms engaged by anterior corti-cal (cingulate and prefrontal cortices).
(15) In practical terms, tests 
are usually provided of sustained attention , which might include 
detecting infrequent visual or auditory targets in ‘continuous performance’ tasks over a protracted period of several minutes. 
Vigilance , the capacity to detect rare targets over very long time

Vigilance , the capacity to detect rare targets over very long time 
periods, is rarely assessed, for obvious practical reasons. The capac-ity for selective attention  is very important to assess in psychiatry 
because of the evident distractibility of patients with anxiety, psychosis, or attentional deﬁ  cit/hyperactivity disorder. Selective

265
attention can be assessed with a variety of tests including the Stroop 
task, the Eriksen Flanker paradigm, or the Posner covert spatial attentional task. In the Stroop test, for example, the subject is required to name the ink colour of congruent or incongruent colour words (e.g. the word GREEN prinked in red ink). Resolution of response conﬂ  ict is a key feature of this test, which has been 
associated with anterior cortex function through extensive investi-gation with functional brain imaging.
(16) The Stroop test has been 
much used in psychiatry, both in its standard form and in various adapted forms with disorder-relevant stimuli. In the Alcohol Stroop, for example, alcohol-related stimuli (e.g. BOTTLE in red ink) may also interfere with naming of the ink colour in patients with alcohol-dependency problems.
There is, in fact, considerable overlap between tests of working

There is, in fact, considerable overlap between tests of working 
memory, attention, and what is termed executive function. The notion of a set of control functions that optimize performance is controversial but seemingly necessary in accounting for performance on complex tests involving planning and decision-making. Planning is generally measured by such tests as the 3-disc T ower of London task, which requires subjects to move discs in one array to match the goal arrangement of another. The test is especially useful in its form where the subjects are not allowed to move the discs but are required to visualize and plan the solution in their ‘mind’s eye’ . Validation of this test as being sensitive to frontal lobe function has come from the study of patients with neurosurgical lesions of the frontal lobe and also functional brain imaging.
(17) However, it should be realized that

(17) However, it should be realized that 
there is no such thing as a ‘frontal lobe’ test; this is evident for exam-ple from studies of patients with basal ganglia lesions and also from the demonstration of an extensive neural network that is activated during spatial planning performance. The T ower of London is a planning task where there is one goal only, whereas many real life situations that overwhelm psychiatric patients require the optimiza-tion of performance on several task simultaneously. This requires high level planning and scheduling of behaviour, as tapped by the ‘Six Elements T est’ in which six different tasks have to be completed.
A further cluster of executive tasks tap into higher-level emo-
tional and affective processes, which appear to be associated with the inferior parts of the frontal lobes including the ventromedial prefrontal cortex. Famous neurological case studies like Phineas

tional and affective processes, which appear to be associated with the inferior parts of the frontal lobes including the ventromedial prefrontal cortex. Famous neurological case studies like Phineas 
Gage and EVR displayed profound changes in personality, social behaviour, and judgement after lesions to this brain area. These processes are also often defective in psychiatric disorders such as

Gage and EVR displayed profound changes in personality, social behaviour, and judgement after lesions to this brain area. These processes are also often defective in psychiatric disorders such as 
bipolar disorder and schizophrenia, which resemble in some respects, the problems in everyday life encountered by patients with ventromedial prefrontal cortex lesions. The Iowa Gambling Task is a measure of emotional decision-making that was devel-oped for the assessment of such patients. The Iowa task allows sub-jects to ‘play’ with four decks of cards which vary in their pay-offs, such that two risky decks are associated with attractive short-term gains but with heavy occasional penalties over time. Typically, patients with ventromedial frontal lesions persist in selecting from these ‘dangerous’ decks, despite accruing considerable debt, and comparable neuropsychological deﬁ  cits have also been seen in neu-
ropsychiatric conditions, particularly drug dependence.
(18) These

(18) These 
tasks also draw on concepts of inhibitory control over behaviour, as there is a requirement to suppress responses that have either become dominant through repeated practice, or that are superﬁ  -
cially attractive by virtue of immediate reinforcement.Speciﬁ  c applications of neuropsychological tests to 
psychiatric disorders
(a)  Standardization of neuropsychological assessment in 
schizophrenia
Now that cognitive deﬁ  cits have been realized to be a core problem 
in schizophrenia, there is increasing attention being focused on the nature of these cognitive deﬁ  cits and how to remediate them, for 
example by novel pharmacological treatments. In order to facilitate this process, NIH funded researchers to perform a meta-analysis of the cognitive deﬁ  cits in schizophrenia in order to determine a pro-
ﬁ le of deﬁ  cits and to construct a battery that would be sensitive to 
those deﬁ  cits and to possible remediation.

(19) They provided a 
principal component analysis suggesting cognitive impairments to be present in seven major domains: attention and vigilance, visual long-term memory, verbal long-term memory, working memory, reasoning and problem solving, psychomotor speed, and social cognition.
(7) In fact, there was not very much published evidence 
for prominent deﬁ  cits in the latter, but the investigators felt that it 
was justiﬁ  ed to include it on the basis of clinical judgement. This

was justiﬁ  ed to include it on the basis of clinical judgement. This 
led secondarily to the construction of a test battery for those domains, with a major requirement being its test–retest reliability. This battery is being used now in clinical trials and so it is too early to assess its utility. As with many other initiatives to provide a stan-dard battery, this carries with it both advantages and disadvantages. A consensus battery is clearly of enormous value and aids the col-lection of data across multiple sites. Hard decisions do have to be made about the trade-off of reliability with validity and sensitivity and committees have to make compromises because of the difﬁ  cul-
ties of addressing these sometimes intangible issues. For example, the Wisconsin Card Sort test is clearly sensitive to deﬁ  cits in schizo-
phrenia, but it does have relatively poor test–retest reliability

phrenia, but it does have relatively poor test–retest reliability 
because of its intrinsic changes of contingency and requirement for 
cognitive shifting, and so has been excluded. However, it is possible that performance on such a test would be sensitive to cognitive enhancing drugs. Similarly, all tests using verbal material are prob-lematic because of the need to provide translated versions whose reliability and relationship to the existing test has to be reassessed to determine its validity. Once batteries such as MATRICS are adopted it is sometimes difﬁ  cult for innovative methods based on 
other theoretical perspectives, such as contemporary cognitive neuroscience to be developed. However, the recognition of a domain of cognitive function, social cognition, for which there are relatively few standardized instruments available has been useful for motivating new research and test development in that area. The ﬁ nal crucial issue, which has a much more general applicability

than the MATRICS battery, is the need to relate the proﬁ  le of 
deﬁ cits obtained to sensitive and reliable measures of functional 
outcome.
(b) Early detection of Alzheimer’s disease
Alzheimer’s Disease (AD) is a chronic and severe form of dementia that is increasing in prevalence as improved health care extends life expectancy. AD patients typically present with deﬁ  cits in episodic 
memory; that is, memory for speciﬁ  c events or experiences that 
can be deﬁ  ned in time and space. AD poses an important challenge 
to neuropsychologists, to facilitate the early detection of the illness, so that future generations of pharmacological interventions may be administered to patients at the earliest opportunity, so that the 2.5.5 neuropsychological basis of neuropsychiatry

SECTION 2  the scientific basis of psychiatric aetiology 266
rapid decline may be slowed, or eventually, halted. Individuals in 
the prodrome of AD often report subjective memory problems but do not fulﬁ  l clinical criteria for AD, in that activities of daily living 
and non-memory cognitive faculties are intact. This condition is referred to as Mild Cognitive Impairment (MCI) or ‘Questionable Dementia’ . There is accumulating evidence that the Paired Associates 
Learning test in the CANTAB assessment may be sensitive to the early stages of AD. PAL is a non-verbal test of learning and memory that requires the subject to associate abstract visual patterns with a series of box locations on a computer screen. Successful perfor-mance relies on learning the conjunction of shape and location; the task cannot be solved by learning either shape or location alone. The task increases in difﬁ  culty from one to eight patterns, and the

task is terminated if the subject fails repeatedly at a given stage.
PAL performance was previously shown to be defective in 
patients with mild Alzheimer’s disease, and test scores could discriminate AD from other neuropsychiatric conditions with sim-ilar symptom presentation, including Fronto-T emporal Dementia and unipolar depression.
(20) Recent studies of ‘at risk’ older adults 
with MCI or Questionable Dementia have reliably isolated a sub-group of cases who have an increased likelihood of converting to a full AD diagnosis by the time of a follow-up assessment. PAL per-formance in the baseline assessment could be used to accurately predict the conversion from Questionable Dementia to an AD diagnosis.
(21) Through a combination of age, PAL score, and per-
formance on the Graded Naming test, subjects with Questionable Dementia could be classiﬁ  ed with 100 per cent accuracy into those 
who did or did not convert to probable AD at a 32-month follow-up.

(22) These neuropsychological measures display both sensitivity, 
in reliably detecting the progression to AD in a subclinical sample, as well as specificity, in differentiating AD from depression. A strong programme of translational research with the PAL task suggests this utility may stem from the critical role of medial temporal lobe structures in visuo-spatial associative learning.
(c)  Relating neuropsychiatric disorders to speciﬁ  c impairments 
in executive function: ADHD, OCD, and mania
Recent biological analyses of such disorders as bipolar illness,

Recent biological analyses of such disorders as bipolar illness, 
ADHD, and OCD have focused on the importance of providing objective measures of performance that relate strongly to the clini-cal symptoms themselves, but that also provide sensitive indices of the underlying pathophysiology. These markers are often referred to as endophenotypes, a term that draws a further link to the putative genetic susceptibility to these conditions. One example is the profound deﬁ  cit in thinking and decision-making that is a 
characteristic symptom of mania—a recent study has been able to demonstrate deﬁ  cits in decision-making in patients with mania 
in the context of a gambling task.
(23) What was especially striking 
about that study was that one of the main measures of quality of decision-making correlated signiﬁ  cantly with symptom ratings on 
the Y oung Mania scale.

ADHD is a spectrum disorder with several sub-types that are 
characterized by the prominence of different clusters of symptoms 
that may be related to different underlying psychological constructs, 
neural and neurochemical substrates, and genetic factors.
(24)
Prominent among these is the so-called hyperactive/impulsive 
sub-type, which then requires sensitive and reliable measures of behavioural inhibition. One commonly used test is the Go-No-Go type task. In perhaps its most sophisticated form, this task measures 
the capability to countermand a speeded response (the ‘stop signal reaction time (SSRT) task). The speed of the SSRT has been related to the volume of damage in the right inferior frontal gyrus in patients with frontal damage.
(25) The task is also robustly

(25) The task is also robustly 
impaired in children and adults with ADHD, and this deﬁ  cit can 
be remediated by psychostimulant treatment with drugs such as methylphenidate.
(26)
OCD may also relate to pathology in executive functions. The 
compulsive component in particular may arise from the repeated selection of a response option long after that option has ceased to be beneﬁ  cial or contextually appropriate. This symptom may be 
operationalized in a neuropsychological setting in two comple-mentary ways. First, there may be a failure to suppress a previously reinforced response, comparable to the deﬁ  cit reported above in 
ADHD. Second, there may be a failure to ﬂ  exibly shift responding

ADHD. Second, there may be a failure to ﬂ  exibly shift responding 
to the newly-relevant mode. These processes can be assessed with some further tasks that are frequently employed in the assessment of psychiatric patients. For example, the Wisconsin Card Sorting test requires subjects to learn a rule on the basis of trial-and-error feedback and then to shift that rule according to altered feedback. OCD patients, like neurosurgical patients with frontal lobe lesions, 
display perseveration where they continue to sort cards according 
to the previously reinforced rule. Performance on a similar set-shifting test has been shown to be impaired not only in patients with OCD, but also in their ﬁ  rst-degree relatives, implying that this 
capacity for cognitive ﬂ  exibility may provide a suitable endophe-

notype for this disorder. Structural and functional neuroimaging data support a neuropsychological account that implicates the orbitofrontal region and interconnected (ventral) striatal circuitry in the pathophysiology of this condition.
(27)
Psychiatry is the science of psychopathology, and as such, the measurement of behaviour and cognition is central to its theory and methodology. Neuropsychology provides such measures, which can be used to augment the psychiatric interview and other clinical instruments, as well as to provide an interface with other important approaches including functional brain imaging (see Dolan, this volume), functional genomics, and clinical psychophar-macology. Clinical neuropsychology has developed via the need to assess brain-damaged patients, whereas in most neuropsychiatric disorders, such damage is much less well deﬁ  ned if it is present at all.

Thus, whilst there is growing information about speciﬁ  c brain 
abnormalities in many forms of neuropsychiatric disorder, the lesion model is not necessarily the most appropriate. Moreover, some of the deﬁ  cits in disorders such as depression and anxiety 
involve subtle interactions between speciﬁ  c emotional and atten-
tional mechanisms with cognitive function. Therefore, the study of 
neuropsychiatric patients has also enriched our understanding of clinical neuropsychology. We predict that these aspects of the disci-pline will develop considerably in the next few years, particularly in combination with data from other domains such as functional brain imaging and pharmacogenetics. Indeed, the speciﬁ  cation of 
speciﬁ  c neural systems implicated in core behavioural or cognitive 
processes may well aid the enterprise of psychiatric genetics by pro-viding more precise deﬁ  nitions of phenotypes (or endophenotypes)

267
than are currently feasible in nosology (e.g. as deﬁ  ned by the 
Diagnostic and Statistical Manual).
A further theme for the future that can readily be envisaged is 
the development of neuropsychological methods for children and adolescents that are more suitable in a psychiatric context. We can predict that there will be an increasing emphasis on ‘lifespan’ studies that potentially will enable the origins of many psychiatric disorders and prodromal states to be identiﬁ  ed. Thus, it will be

necessary to examine cognitive function, including under-researched areas such as ‘social cognition’ , in longitudinal terms with tests that can be administered appropriately at different points in the lifespan. Allied to this will be pressure to make tests less ‘laboratory-bound’ and more predictive of everyday functioning at school or in the workplace. One technological advance that may facilitate all of these requirements would be through the use of ‘virtual reality’ software, and also the collection of norms on a mas-sive scale by utilizing web-based data collection. It is to be hoped that psychiatry will encourage and embrace such developments, rather than rely on the traditional methods.
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29, 399–419.2.5.5 neuropsychological basis of neuropsychiatry

2.6
The contribution 
of social sciences
Contents
 2.6.1 Medical sociology and issues of aetiology
salience for psychiatry
2.6.1 Medical sociology 
and issues of aetiology
David Mechanic, in his pioneering textbook, Medical Sociology ,(1)
views human activity within an adaptive framework—as a strug-
gle of human beings to control their environment and life situa-tion. While this view informs the research to be outlined, there are a number of ways it differs in emphasis from much medical soci-ology. First, by its concern with particular disorders deﬁ  ned in 
medical terms. Second, by its use of the investigator rather than respondent to characterize phenomena—to decide, for example, whether an incident should be classiﬁ  ed as a life event. Third, by

medical terms. Second, by its use of the investigator rather than respondent to characterize phenomena—to decide, for example, whether an incident should be classiﬁ  ed as a life event. Third, by 
the importance placed on context. In order, for example, for an investigator to make a judgement about the likely meaning of an event such as a loss of a job it is essential to know whether it cast the person in a bad light; its impact on the person’s family; her chance of getting another job, and so on. It is such circumstances 
surrounding an event that usually give it meaning via the emotion 
they create. Finally, by recognizing that where appropriate such emotion should be taken into account: ‘A world experienced with-out any affect would be a pallid, meaningless world, and it is what gives us feedback about what is what is good or bad about our lives’ .
(2)Context and measurement

Concern with context in the social sciences was central to the prob-lem of meaning discussed widely in Germany in the late nineteenth century; and the ideas were introduced into sociology by Max Weber
(3) and into psychiatry by Karl Jaspers,(4) although no one 
showed how to apply the methods systematically to concrete exam-ples.
(5) Jaspers, in his Allegemeine Psychopathologie , emphasized 
the way in which Verstehen , or understanding, on the part of an 
investigator ‘depends primarily on the tangible facts’ (i.e. verbal contents, cultural factors, people’s acts, ways of life, and expressive gestures) in terms of which the connection is understood, and which provides the objective data.
(4) While this view inﬂ  uenced the

(4) While this view inﬂ  uenced the 
approach to meaning in what follows, there is a critical difference. No attempt has been made to make a judgement about the presence of a causal link between a set of circumstances and a psychiatric episode. The investigator has to judge only the likely meaning of a set of circumstances in the light of ‘tangible facts’ about a person’s past and present. Any link with disor der is explore d using esta blished 
scientiﬁ  c procedures.
As noted by Jaspers, it is possible to take note of cultural factors; 
for example, when rating the likely implications of a birth, as part of research among women in a black township in Zimbabwe, investigators took into account the cultural importance on a wife producing a male child for her husband and his family.
(6)
A second, more limited, use of context deals with the actual

(6)
A second, more limited, use of context deals with the actual 
observation of emotion. For example, the Camberwell Family Interview, by taking account of vocal (in contrast to verbal) aspects of speech, for example, establishes how far a parent’s talk about a child conveys ‘criticism’ rather than ‘dissatisfaction’ .
(7) The approach 
can be extended to deal with core sociological concepts such as role commitment. For example, mothers in North London have been shown to differ substantially in commitment to roles such as ‘mother’ or ‘wife’ judged by how enthusiastically associated activities are discussed.
(8) The relevant context is limited to the 
interview itself and what this conveys about a person’s emotional style. In everyday life we automatically make allowances for the fact, for example, that some people show warmth in a more open way and, by taking this into account, makes it is possible for different expressive styles to be treated as equivalent.

269
Some methodological considerations
These developments have enabled ‘soft’ variables to be quantiﬁ  ed. 
It has also been possible to make a reasonably persuasive case that signiﬁ  cant bias has not followed the use of the investigator as the 
measuring instrument. For example, Creed
(9) in a study of appen-
dectomy found a relationship between severely threatening events rated contextually and the onset of non-inﬂ  amed but not inﬂ  amed 
conditions. This result was persuasive for two reasons. First, on the basis of a detailed description of the event and surrounding circumstances a consensus rating team reached agreement about the likely degree of threat, blind to what the person conveyed she felt and to whether she was a patient. Second, Creed, who provided the team with this edited account, was blind to clinical details. (He consulted medical records after the ratings had been made.) Such ﬂ  exibility is difﬁ  cult, if not impossible, with a questionnaire-

based instrument which hands over the task of measurement to the respondent.
There are now a number of investigator-based instruments 
developed to deal with psychiatric issues covering areas ranging 
from ‘expressed emotion’ (e.g. critical comments, warmth, etc.), attitudes to self (e.g. self-esteem), plans and concerns (e.g. commit-ment to various roles), behavioural systems (e.g. styles of attach-ment), experience of adver sity in childhood (e.g. sexual and physical 
abuse), and characteristics of non-family groups (e.g. restrictive-ness of a psychiatric ward regimen). Around each a fair amount of replicable and theoretically relevant findings have emerged. Particularly important was the development in the 1960s of the clinically informed interview-based Present State Examination (PSE) by Wing et al .
(10) later amended to deal with a 12-month 
period,(11) and psychosocial measures such as that of ‘expressed 
emotion’(12) and the Life Events and Difﬁ  culties Schedule.(13) Part

emotion’(12) and the Life Events and Difﬁ  culties Schedule.(13) Part 
of the strength of the resulting research has been due to the levels of inter-rater reliability achieved and the ability of the approach to deal with time order. It is often overlooked that even with longi-tudinal designs it can be important to be able to establish what has happened between interviews.
Life events and building aetiological models
The characteristic features of the aetiological studies that have emerged can be illustrated by those dealing with life events. The signiﬁ  cance of ﬁ  ndings concerning depression is enhanced by the 
fact that most studies have produced broadly consistent ﬁ  ndings 
about the role of events.
(14–16)  Indeed, for some years the challenge

(14–16)  Indeed, for some years the challenge 
has been not so much to establish the presence of an effect, but to learn more about the nature of the events involved and to integrate ﬁ ndings into a more comprehensive aetiological model.
(17)
The role of life events in the aetiology of depression
(a) Measurement and meanings
The original version of the Life Events and Difﬁ  culties Schedule was 
developed to study schizophrenic episodes(18) and there has since 
been a good deal of research dealing with psychotic patients.(19) An 
early achievement in the study of depression was to make clear that the amount of change in activity as such appears to be irrelevant and that the impact of events results from their meaning.
(13) It has also 
been clear that attention needs to be given to ongoing difﬁ  culties that

been clear that attention needs to be given to ongoing difﬁ  culties that 
can either be brought about by an event (e.g. the death of husband leading to ﬁ  nancial problems) or lead to an event (e.g. a marital 
difﬁ culty eventually ending in a separation).
In dealing with meaning, two perspectives have proved productive. 
The ﬁ  rst is summed up by the statement that we cannot fully know 
the meaning of an event until we relate it in some manner to our 
concerns. One way of conceiving of these is in terms of the impact of a particular event on plans and purposes that stem from role activity caught up in the crisis: how, for example, being turned down for rehousing by a local authority thwarts a woman’s wish to move from an overcrowded and damp ﬂ  at to give her children 
‘a better start in life’ .
A second perspective concerning meaning assumes the likely

A second perspective concerning meaning assumes the likely 
presence of evolutionary-based response patterns that help to guide us in terms of what to want or to avoid, and that such systems are sensitive to a particular range of stimuli. The attachment system and fear responses are obvious examples.
(20, 21) Of course, such 
responses will be inﬂ  uenced by individual differences of various 
kinds and by cultural display rules concerning emotions, but there is good reason to believe that such systems are often involved in the development of psychiatric disorders. For example, the central importance in a number of cultures of ‘critical comments’ of a close relative rather than ‘dissatisfaction’ in a schizophrenic relapse prob-ably reﬂ  ects an evolutionary-based sensitivity to emotionally toned 
criticism interacting with some constitutional predisposition to the disorder.
(22)
The Life Events and Difﬁ  culties Schedule deals with both kinds of

(22)
The Life Events and Difﬁ  culties Schedule deals with both kinds of 
meaning. Blind consensus ratings usually based on four-point scales, made by several members of a team are employed to rule out report-ing artifacts using ‘edited’ accounts supplied by the person who car-ried out the interview as discussed earlier in relation to the study of appendectomy. General as well as speciﬁ  c kinds of threat are rated

in this way. They are contextual in the sense of taking into account a person’s likely concerns of relevance for the event insofar as these can be assessed from a person’s current circumstances and biogra-phy. In making such ratings no account is taken of reported feelings or whether a disorder followed the event. It deals not only with pos-sible bias on the part of raters, but also with the problem that the cognitive processes involved in the appraisal of an event are not nec-essarily ones a person is willing or able to report.
(23) General guide-
lines for rating severity of threat are given in an extensive manual containing thousands of examples listed in terms of a number of event categories (such as ‘demotion at work’ and ‘unplanned preg-nancy’). A similar procedure is followed for ongoing difﬁ  culties.
Some ﬁ  ndings concerning depression
The ﬁ  rst use of the Life Events and Difﬁ  culties Schedule to study

The ﬁ  rst use of the Life Events and Difﬁ  culties Schedule to study 
depressive conditions took place in the early 1970s and involved a patient series seen at the Maudsley Hospital together with a sample of women from the local Camberwell population. A threshold of ‘caseness’ reﬂ  ected what an outpatient psychiatrist would accept as 
a ‘case’ .
(13) This enquiry, and a number made later, have established 
that the majority of episodes of clinical relevance are preceded by a severely threatening event.
(14–16)  These at a minimum had to 
be judged to continue to convey threat for at least a further 10 to 14 days. Nothing emerged to suggest that events with only short-term threat play a role.
Table 2.6.1.1 gives a typical result from a prospective enquiry of 
400 women living in Islington in North London with at least one child at home. The table shows that 29 of the 32 onsets in the ﬁ  rst 2.6.1 medical sociology and issues of aetiology

SECTION 2  the scientific basis of psychiatric aetiology 270
follow-up year were preceded by at least one severe event in the 
prior 6 months with most occurring within a matter of weeks.(8,23)
For example, a woman experiencing a second miscarriage after persistent attempts to have her ﬁ  rst child would probably have the 
event rated severe, but a ﬁ  rst miscarriage shortly after marriage 
would most likely be rated upsetting but not severely so.
This ﬁ  nding emerged despite the use of contextual ratings that, 
as made clear, are based on a limited amount of information and deliberately designed to be approximate and probabilistic. It was also possible to obtain more direct evidence about the relevance of plans and purposes by a measure of emotional commitment to var-ious roles made at the time of the ﬁ  rst interview based on how they

were talked about. Where a severe event (e.g. a child’s delinquency) in the follow-up year ‘matched’ an area of high emotional commit-ment (e.g. to motherhood), risk of an onset was considerably 
increased when compared with a non-matching severe event.
(8)
The contextual approach has also been used to take account 
of more speciﬁ  c aspects of meaning. Severe events preceding 
an onset of depression generally involve loss, if this is deﬁ  ned 
broadly not only in terms of loss of a person but loss of a role or a cherished idea—the latter about oneself or someone close.
(24)
(In contrast, events preceding the onset of anxiety tend to involve ‘danger’—the threat of future loss.
(25)) However, although loss is 
typically present it may not be the factor of central aetiological importance. Table 2.6.1.2 illustrates this by the development of a more comprehensive rating scheme—again carried out by the

typically present it may not be the factor of central aetiological importance. Table 2.6.1.2 illustrates this by the development of a more comprehensive rating scheme—again carried out by the 
investigator. Four overall types of meaning are considered, cover-ing in all nine categories. The ratings are hierarchical. Where more 
than one rating is possible the highest on the scale is taken. The ﬁ  rst 
three categories concern possible types of humiliation , i.e. the like-
lihood of the event provoking a sense of being put down or a marked devaluation of self. The ﬁ  rst category, for example, covers 
separating from a partner or a lover where they either took the ini-
tiative or the respondent was ‘forced’ to leave or break off a rela-tionship because of violence or the discovery of inﬁ  delity.
Events associated with entrapment , the second main type, had

Events associated with entrapment , the second main type, had 
to have failed to meet criteria for one of the three humiliation categories. Such events emphasized the fact of being imprisoned in a punishing situation that had gone on for some time. The third type deals with four kinds of loss (in the absence of humiliation or 
entrapment) with the ﬁ  nal type, danger , involving threat of a 
future loss.
(24)
The table shows whether a particular severe event (or sequence

(24)
The table shows whether a particular severe event (or sequence 
of closely related events) was followed by an onset of depression, taking the event (or sequence) nearest to the onset when there was more than one event within 6 months of onset. Using a 2-year period for the Islington women, it shows that there were large differences in risk by event type. If events involving humiliation are combined with those of entrapment, risk was increased three-fold.
(24) The relatively low risk of depression associated with loss 
alone, except following a severe event involving a death, suggests that while the majority of events involve loss, something more than this is usually involved and that the experience of humiliation or entrapment associated with the loss is often critical.

So far I have discussed only studies dealing with depressive onsets in the general population, almost entirely of a ‘neurotic’ kind. In the Camberwell enquiry of psychiatric patients, while events were rather less frequent before ‘melancholic’ than before ‘neurotic’ depression, there was considerable overlap between the two types. This lack of a clear link between the presence of a provoking life event and type of diagnosis had been reported earlier
(26) and also 
in several subsequent studies.(27,28)
A recent study of North London psychiatric depressive patients 
has thrown possible light on this somewhat unexpected picture. When episode number was taken into account, those patients with both a melancholic/psychotic diagnosis and a prior episode of depression had a much smaller chance of experiencing a severe event before onset.
(29) A patient series from Pittsburgh produced 
consistent ﬁ  ndings.(30) These results, if conﬁ  rmed, may also help to

consistent ﬁ  ndings.(30) These results, if conﬁ  rmed, may also help to 
explain inconsistencies in published results since the proportion with a melancholic/psychotic picture and a prior episode is bound to vary by type of treatment centre. It is also of note that this same London study concluded that, despite detailed questioning, as many as one-tenth of patients  with a ‘neurotic’ depressive dis order 
gave no hint of being provoked by social adversity of any kind.
(24)
It is of interest that the smaller number with provoking events as 
episode number rises has also been found to relate to the course of bipolar conditions where there is some evidence for a sensitization or kindling mechanism.
(31) Important research continues to 
emerge about psychosocial risk factors and bipolar conditions(32)
and other psychiatric conditions.(33) However, for this brief review

and other psychiatric conditions.(33) However, for this brief review 
I will continue to focus on common depressive disorders.Table  2.6.1.1  Onset of depression within 6 months of a severe event 
or a severe difﬁ  culty among 303 women in Islington
Percentage onset
Severe event 22 (29/130)
Severe difﬁ  culty and no severe event  5 (1/20)Neither  1 (2/153)Total 11 (32/303)
Table 2.6.1.2  Onset by type of severe event over 2-year period in 
the Islington community series
Hierarchical event classiﬁ  cation No. of 
onsetsPercentage 
onset rate
(a) All ‘humiliation’ events 31/102 30

onset rate
Humiliation: separation 12/34 35Humiliation: other’s delinquency 7/36 19Humiliation: put down 12/32 38(b) All ‘trapped’ alone events (i.e. not (a)) 10/29 34(c) All ‘loss’ alone events (i.e. not (a) or (b)) 14/157 9Death 7/24 29Separation: subject initiated 2/18 11Other key loss 4/58 7Lesser loss 1/57 2(d) All ‘danger’ alone events (i.e. not (a), (b), or (c)) 3/89 3All severe events 58/377 15

271
Course and remission
Life-event research has also thrown some light on the processes 
involved in remission from depression. Evidence has begun to 
emerge that these often involve the reverse of the process leading 
to onset. A ‘positive’ event or the reduction in the level of a severe 
difﬁ culty (with or without an event) is commonly found to have 
been present in the 20-week period before any remission (or 
marked improvement). However, it is of interest that although the 
events involved were rated contextually as likely to have given 
renewed hope about the future, one-third were at the same time 
judged as severely threatening.(34)
In the Islington general population series somewhat over half 
of the remissions of episodes that had lasted 20 weeks or more 
were preceded by such an event. There was no such link with 
episodes lasting less than this. In the patient series the result 
was much the same, although the chances of a positive event or

was much the same, although the chances of a positive event or 
difﬁ culty reduction for those on antidepressant medication was 
somewhat less.(35)
A different approach to the issue of outcome concerns determi-
nants of the length of a particular episode. Here the presence of 
severe interpersonal difﬁ  culty at the point of onset (but no other 
difﬁ culty) was an important predictor of whether a depressive 
episode would go on to last for at least 1 year, and this held for a 
general population and patient series.(36, 37) Ongoing difﬁ  culties 
therefore need to be taken into account in terms both remission 
and in terms of whether an episode takes a chronic course.
Psychosocial vulnerability
The part played by severe events in depression has proved to be 
a particularly effective platform for exploring psychosocial vulner-

ability. The importance of this question was, in fact, illustrated in 
Table 2.6.1.1 where, despite the fact that the majority of onsets were 
preceded by a severe event, only one-ﬁ  fth of those who experienced 
a severe event developed depression. While, as already discussed, 
taking account of event type increases this to one-third, it is still 
necessary to ask why only a minority go on to develop clinically 
relevant depression following a severe event.
In the Islington series, two background factors present at the 
time of the ﬁ  rst interview proved highly predictive of onset: a nega-
tive environmental factor (negative interaction with others in the 
home and in addition, for single mothers, lack of a close conﬁ  dant 
seen fairly often) and a negative psychological factor (negative

seen fairly often) and a negative psychological factor (negative 
evaluation of self). (The presence of chronic anxiety or subclinical 
depressive symptoms has often been included in the latter index, 
but ﬁ  ndings are broadly similar with only negative evaluation 
of self.)
Their predictive power can be judged by the fact that, while only 
23 per cent of the women without depression at the time of ﬁ  rst 
contact had both, three-quarters of onsets in the 12-month follow-
up occurred among these women.(38) The result has recently been 
conﬁ  rmed in a second prospective enquiry.(39)
In terms of an overall aetiological model, the predictive power of 
the two indices appears to be largely a result of relating to a greater 
chance of a severe event occurring and to a lack of effective emotio nal 
support from a close conﬁ  dant once the event has occurred.(40–43)

Consideration of social support, of course, links the research, with 
social science concepts such as ‘social integration’ , ‘social bond’ , and 
‘social alienation’ .(5) The topic is too complex to pursue in any detail in the present brief review. Research has so far underlined 
the need to recognize that support at one point in time does not 
necessarily predict what will occur in a subsequent crisis and, 
indeed, that a signiﬁ  cant aspect of a number of severe events is the 
fact they involve the withdrawal of social support that up to that 
point had largely been taken for granted.(43, 44) There is also some 
indication that the ability of a woman to make supportive ties that 
can be used in a future crisis, and also to use them in such circum-
stances, is adversely inﬂ  uenced by the early experience of childhood

stances, is adversely inﬂ  uenced by the early experience of childhood 
abuse and neglect.(45, 46)
Figure 2.6.1.1, dealing with the Islington series, sums up research 
on the issue of vulnerability. It takes into account both event type 
and vulnerability and it shows that a severe event, however threat-
ening, was not enough to provoke depression without the presence 
of at least one of the two vulnerability risk factors. Subsequent 
research has conﬁ  rmed this general picture.
Gender differences
Most research on depression using the Life Events and Difﬁ  culties 
Schedule has dealt with women, although in the original 
Camberwell enquiry a small series of men gave similar results, as 
did a subsequent population enquiry.(24) However, recent research 
has gone further to suggest that the well recognized greater risk of 
a depressive onset among women may relate to their greater sensi-

tivity to severe events involving their role as mothers. In a study of 
couples experiencing a severe event in common, women were twice 
as likely to develop a depressive episode following events involving 
procreation, children, and housing; for other events, risk was much 
the same.(47) While this study requires replication, it does support 
the increasingly held opinion that the large gender difference in the 
experience of ‘neurotic’ depression is likely to have an essentially 
psychosocial explanation.(48)
A lifespan perspective
So far only current environmental circumstances have been taken 
into account. The Camberwell research also identiﬁ  ed loss of a 
mother before the age of 11 as a risk factor.(43) While there has been 
a good deal of controversy about this ﬁ  nding,(49, 50)  two further

a good deal of controversy about this ﬁ  nding,(49, 50)  two further 
population studies produced equally clear evidence with the added 
suggestion that such a loss between 11 and 17 may also increase 
Fig. 2.6.1.1 Onset rate among 130 Islington women with a severe event by type 
of event and number of background risk factors.
2.6.1 medical sociology and issues of aetiology

SECTION 2  the scientific basis of psychiatric aetiology 272
risk.(51, 52) The mode of the impact of such an early loss of mother 
for women is undoubtedly complex, but several studies have now 
established the critical importance of untoward experiences during 
childhood after  the loss and have downplayed the role of loss as 
such.(51) More important than the loss of the mother itself was the 
quality of replacement parental care (in terms of an index of 
parental indifference or lax control). Risk of adult depression was 
doubled for those positive on the index.In order to understand its 
link with later adult depression it has been necessary to trace the 
history of a woman from the loss itself to such depression in a way 
that makes it possible to gain some sense of a life trajectory. Certain 
early experiences are particularly associated with the chance of 
experiencing the kind of adult factors already discussed.(53)

A factor playing a critical mediating role was the experience of a 
premarital pregnancy, and, like the care index itself, this was found 
to be associated with the subsequent experience of severe events. 
What seemed to be crucial about these premarital pregnancies was 
that they often trapped women in relationships which they might 
well not otherwise have chosen and which became a source of 
ongoing problems—such as severe housing and ﬁ  nancial difﬁ  cul-
ties consequent upon a couple starting a family too young to have 
built up adequate savings, or marital difﬁ  culties with undependa-
ble partners. These women also emerged as less upwardly mobile, 
in terms of social class, than their peers without such pregnancies. 
In interpreting this complex of experiences, a conveyor belt of 
adversities was outlined, on which some women often appeared

adversities was outlined, on which some women often appeared 
to move inexorably from one crisis to another, starting with lack of 
care in childhood and passing via premarital pregnancy to current 
working-class status, lack of social support and high rates of severe 
events.(53)
Although it was often hard to see from the women’s accounts of 
their lives how they could have left this conveyor belt once their 
childhood had located them on it, a more personal element is likely 
to have played a role in many instances. Here the work of Quinton 
and Rutter(54–57)  has been particularly signiﬁ  cant in developing a 
lifespan perspective in this regard, and over this issue the results of 
the two research programmes have largely complemented each 
other.
The kind of early adverse experience just outlined was subse-

other.
quently incorporated into a broader index of childhood adversity 
that included severe physical abuse within the family and also 
severe sexual abuse in any setting.(58) This index not only relates to 
a doubling of the risk of a depressive onset in adult life, but also 
to a number of other adverse outcomes, for example to the quadru-
pling of risk of an episode taking a chronic course(59) and also to 
the risk of a depressive condition comorbid with anxiety disorder 
deﬁ ned by DSM-IIIR criteria (excluding simple phobias and mild 
agoraphobia).(60) It can be added that the retrospectives measures of 
early maltreatment used in these enquiries appear to be sufﬁ  ciently 
free of bias to enable the ﬁ  ndings to be taken seriously.(61, 62)
A population perspective
It is useful also to consider ‘neurotic’ conditions that form the bulk

It is useful also to consider ‘neurotic’ conditions that form the bulk 
of depressive disorders, even in patient series, in terms of a popula-
tion perspective. Figure 2.6.1.2 summarizes the ﬁ  ndings of six pop-
ulation studies of women aged between 18 and 65 carried out in a 
comparable manner, using the same semi-structured interview-
based measures as in the Islington survey, including the Present State Examination. The bottom half of Fig. 2.6.1.2 shows the rate 
of depressive ‘caseness’ in a 12-month period. Between the two 
extreme populations there is a 10-fold difference—3 per cent in 
a rural Basque-speaking population in Spain(63) and 30 per cent 
in a black urban population in Zimbabwe.(6, 64) In addition these 
rates are fairly closely paralleled by differences in the experience of 
severe events particularly likely to provoke depression (see top half 
of Fig. 2.6.1.2).

One of the implications of these results becomes clear in the 
context of a behavioural genetic perspective. A key point about the 
concept of heritability is that it is speciﬁ  c to a particular population 
and based on consideration of individual discrepancies from a 
population mean. While there may well be a genetic contribution 
in each of the six populations, this would reflect individual 
variability in risk within each population. Even if large, the genetic 
contribution would only be likely to be of relevance for explaining 
the substantial population differences in rates of depression if there 
were large population differences in the frequency of relevant genes. 
On present evidence the most plausible interpretation of such differ-
ences is that they are the result of psychosocial factors.(65)

There is, however, no inherent conflict between the two 
perspectives—they refer to different ways of looking at the 
‘variance’ of a condition.(66) The general point is that the study of 
individual variability within particular populations cannot rule 
out the possibility that the mean level of disorder is largely under 
environmental control; that it can be increased or decreased 
markedly by external changes quite uninﬂ  uenced by the genetic 
make-up of a population.
A population perspective is also concerned with variability in 
rates of disorder within populations in terms of social categories 
such as socio-economic status. Thus, the survey in Camberwell in 
South London in the early 1970s found that, while the rate of severe 
events was related to social class position, this explained compara-

tively little of the large class difference in prevalence of depression; 
of greater importance were background vulnerability factors such 
as an unsupportive marriage.(13) However, the picture has recently 
become more complex with the ﬁ  nding that severe events involving 
Fig. 2.6.1.2 Yearly rate of irregular or disruptive severe events per 100 women in 
six populations and prevalence of caseness of depression in year.

273
humiliation and entrapment are not only especially depressogenic 
but particularly common in high-risk populations (such as Harare) and within populations in high-risk subgroups (such as working-class women in London). In Islington such events were common among single mothers, a social category that has expanded dramat-ically in most western populations in recent years and among whom there is a high risk of depression.
(67)
Final comments
There are two ways of looking at the ﬁ  ndings that have been

(67)
There are two ways of looking at the ﬁ  ndings that have been 
reviewed. First, that the study of life events has been an effective way of opening up wider issues concerning psychosocial factors and the aetiology of depression. This has been possible because, given the presence of a substantial causal link, a platform is pro-vided for the study of a whole range of other experiences. As research has progressed it has pushed back in time to consider the aetiological role of early experiences of neglect and abuse which can have event-like characteristics. In more general terms the study of events has led to consideration of issues of vulnerability and protection, event production, chronicity, and course of particular episodes, and also issues not covered in this account such as coping and social support. It can be added that the work has also led to a good deal of research on other psychiatric conditions that have not 
been reviewed.
(9,18,68,69)

The second contribution of the findings reviewed involves 
the stimulation of cross-disciplinary research concerning the depression—event link itself. This is a complex issue because life events correlate with factors ranging from genetic/personality
(70)
to macrolevel/societal.(65) The growing literature on the role of the 
serotonin transporter gene in depression is of particular interest as evidence has emerged for an important interplay with life events. A recent study has documented an interaction of the s allele variant 
of 5-HTTLPR polymorphism and life events with young adults. It also reported that childhood maltreatment predicted depression only among those with the s allele.
(71) A somewhat similar ﬁ  nding 
with adult twins concerning life events has also been reported.(72)

It is intriguing that there is a possibility of an important develop-mental contribution: that the critical gene-environmental interplay occurs early in life perhaps involving experiences such as parental maltreatment.
(73) However, other studies have had more mixed 
findings with some showing no evidence of an interactive effect.
(74,75)  It is clearly too soon to review ﬁ  ndings with any conﬁ  -
dence—for example, some of the mix ﬁ  ndings may well relate to 
the general failure to utilize the kind of detailed investigator-based measure of life events reviewed earlier and a failure to restrict con-sideration to events occurring not long before onset. In most stud-ies the environmental measures fall a good way short of current best practice, although optimizing such assessments is essential for the detection of gene x environment interaction.
(76,77)  Nonetheless

(76,77)  Nonetheless 
the research is an exciting development and it seems possible that well-established ﬁ  ndings will emerge. But here my earlier com-
ments about the likely critical importance of psychosocial factors in explaining differences in rates  of disorder across populations 
should be kept in mind, although here there is some evidence that 
the genotype for 5-HTTLPR polymorphism may differ across pop-ulations.
(78) It will also be important to take into account diagnos-
tic issues. For example, it would be interesting to explore the fact, mentioned earlier, that it has been possible to isolate a small group of ‘endogenous’ neurotic depressive episodes.
(24) Also it should be

(24) Also it should be 
borne in mind that while this short review has largely restricted itself to work on depression, the life-event approach has been suc-cessfully employed with a number of other psychiatric and physical conditions and the possibility for collaborative research may well be much wider. For example, the s variant of 5-HTTLPR polymor-
phism also appears to be relevant for other psychiatric condi-tions.
(74) There are other relevant biological considerations. The 
ﬁ ndings concerning life events involving humiliation and entrap-
ment may need to be viewed from an evolutionary perspective, that is, that in some way a response pattern closely linked to issues surrounding defeat and exclusion, which has developed in group-living animals, may have functioned to promote survival.
(78,79) It is

(78,79) It is 
possible that clinically relevant depressive conditions are often a complication of essentially non-pathological submission and appeasement responses to defeat in group-living mammals. Therefore, the high rates of clinically relevant depression that appear to be possible in some populations may well be a result of the more highly developed cognitive developments of Homo 
sapiens  together with the event-creating potential of many societies 
experiencing periods of marked social change due to factors such as war, industrialization, technological development, urbanization, changing sexual mores.
(80)
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35. Brown, G.W. (1993). Life events and affective disorder: replications and 
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38. Brown, G.W., Bifulco, A., and Andrews, B. (1990). Self-esteem and 
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41. Edwards, A.C., Nazroo, J., and Brown, G.W. (1998). Gender difference 
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42. Veiel, H.O.F. and Baumann, U. (eds.) (1992). The meaning and 
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44. Andrews, B. and Brown, G.W. (1998). Marital violence in the 
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45. Harris, T.O., Brown, G.W., and Bifulco, A. (1986). Loss of parent in 
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48. Bebbington, P . (1996). The origins of sex differences in depressive

48. Bebbington, P . (1996). The origins of sex differences in depressive 
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51. Harris, T.O., Brown, G.W., and Bifulco, A. (1987). Loss of parent 
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52. Bifulco, A., Brown, G.W., and Harris, T.O. (1987). Childhood loss 
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53. Harris, T.O. (1988). Psycho-social vulnerability to depression: the 
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of depression. Journal of Health and Social Behavior ,43,
255–76.
2.6.2 Social and cultural 
anthropology: salience for psychiatry
Social and cultural anthropology

255–76.
One of the social sciences (together with history, economics, 
political science, sociology, and social psychology), social and cultural anthropology is principally concerned with the study of society, in almost all of its aspects. T ogether with linguistics, archae-ology, and biological anthropology, social and cultural anthropol-ogy formed the classic (and now considered overly ambitious) four-ﬁ  eld base of anthropology, the science of man. Y et still, in 
many universities, anthropology departments bridge the tradi-tional divisions of the humanities, social sciences, and natural sciences. From the outset, anthropologists deﬁ  ned their subject in 
holistic terms meant to contextualize women and men in a nested hierarchy of inﬂ  uential environments that ran from the human

holistic terms meant to contextualize women and men in a nested hierarchy of inﬂ  uential environments that ran from the human 
body to the social body, and that assumed that these levels were related to each other, so that individual and collective processes 
(biological, psychological, social relational, and cultural) intersected 
in some way. Social and cultural anthropology, in particular, took as its subject matter studies of communities, ranging from small-scale preliterate groups to neighbourhoods or institutions in megacities. Comparison of different societies, or different struc-tures and processes in those societies, is still seen as a deﬁ  ning 
approach, as is the analysis of cultural symbol systems (from lan-guages to aesthetics), history of kinship, and other systems of social relationship, as well as research on large-scale social changes such as our era’s globalization, ethnonationalism, and resurgence of religious fundamentalism.

Anthropology’s chief research methodology is ethnography, the 
close study of a local world—a village, an urban neighbourhood, an institution, a network. Ethnography privileges local language, conceptual categories, values, and practices. Its procedure is to begin with local deﬁ  nitions and perceptions of reality (sometimes 2.6.2 social and cultural anthropology: salience for psychiatry

SECTION 2  the scientific basis of psychiatric aetiology 276
called ‘emics’ , from phonemics), and only when these experience—
near patterns are understood in a particular context of everyday life (with the larger political, economic, and cultural forces that inﬂ  u-
ence it) are comparisons made with other local worlds in the framework of experience-distant scientiﬁ  c deﬁ  nitions of reality 
(referred to as ‘etics’ , from phonetics). Knowledge is generated by participant observation, informal interviews, and the use of more formal procedures from structured interviews to questionnaires. Cross-cultural comparison is another core mode of knowledge production. Both ethnography and cross-cultural comparisons draw on empirical data to engage larger questions in social theory, which itself is constantly being reorganized in this dialectical engagement.
In this century, social and cultural anthropology’s division of 
labour has spun off at least two subﬁ  elds that are of particular

labour has spun off at least two subﬁ  elds that are of particular 
relevance for psychiatry: psychological anthropology and medical anthropology.
Psychological anthropology
This subfield grew out of the culture and personality school (ca. 1930–1950), when psychoanalysts and anthropologists sought to collaborate to understand how mental processes differed or were similar across greatly different societies. Margaret Mead, Ruth Benedict, and Irving Hallowell are those anthropologists most often associated with this school. Although, most anthropologists became critical of the basis of the ﬁ  eld in psychoanalysis and a cor-

relation of individuals with entire cultures, a small group of social and cultural anthropologists continue, none the less, to pursue this direction, and over time they have developed broader ties with psychology, as can be readily seen by their leading research interests in cognition, lifecycle development, and ethnopsychological cate-gories. Anthropologists working in this tradition have studied self-concepts and self-images, emotion terms, interpersonal pro-
cesses and their relation to personhood, as well as experiences of 
childhood, child rearing, adolescence, midlife, and ageing. Psychological anthropology has been inﬂ  uential in recent years in 
psychology, where a sister subdiscipline called cultural psychology has started up in close connection to it.
Medical anthropology

Physicians were among the founders of anthropology, and some, like the British polymath W.H.R. Rivers, combined medicine and anthropology. Another source of medical anthropology was social medicine and public health; indeed the great German pathologist and social medicine advocate, Rudolph Virchow, was one of the ﬁ rst to use the term ‘medical anthropology’ . Thus, medical anthro-
pology’s early roots were applied. After the Second World War, the ﬁ eld took off as anthropologists developed an interest in the theo-

retical and empirical aspects of non-Western medical traditions, religious healing and its relation to medicine, and increasingly in experiences of suffering. In more recent years, medical anthropolo-gists, of whom there are several thousand worldwide, have devel-oped special interests in infectious diseases (especially diarrhoeal disease, malaria, tuberculosis, and AIDS), female reproductive life-
cycle problems, the health problems of children and the aged, 
substance abuse, cancer, diabetes, disabilities, medical ethics, and the economic and social transformation of health care. One of the earliest and abiding interests has been in psychiatric diagnosis, disorders, and treatments. This subﬁ  eld of social and cultural

anthropology has many ongoing relationships to cultural psychia-try (see Chapter 2.6.1) and has been active in recent years in the effort to introduce mental health concerns into international health (see Chapter 1.3.2 and 7.3). Indeed, the cultural sections of the DSM-IV were contributed by a taskforce that included both medi-cal anthropologists and cultural psychiatrists, in equal numbers.
Major contributions of anthropology 
Cultural critique of biomedicine
One of the crucial contributions of anthropology is theoretical,

One of the crucial contributions of anthropology is theoretical, 
namely a critique of the theoretical biases inherent in psychiatric science and clinical practice. This may seem self-evident because unlike any other branch of medicine, there is no blood test, biopsy, or radiograph to diagnose psychiatric disorder (leaving aside Alzheimer’s disease, which is after all a neurological disorder). That means that psychiatric diagnosis is based on the establishment of symptom and syndromal criteria, which are based in turn in lan-guage, lay categories, and everyday social experience. Cultural bias can enter this process in several ways. Anthropologists have shown that this can happen when diagnostic criteria that have been devel-oped in one society are applied to another where they lack validity. This is called a ‘category fallacy’ , a term introduced by Kleinman.
(1)

(1)
Classic examples include trance and possession states in many non-Western societies, which are frequently normative and normal experiences. Failure to recognize this phenomenon, and therefore the diagnosis of persons in religious trance as psychotic, creates a category fallacy in the application of the diagnostic criteria of psychosis to normal people. The cultural critique has been applied to personality disorders as well, because this category of disorder models self-processes on a Euro-American, middle-class, and usu-ally male behavioural type and lifestyle. Anthropologists argue for a much more ﬂ  exible and interactive understanding of subjectivity 
that changes in basic ways in response to different social circum-stances.
In the 1990s, cultural critique has been important in highlight-
ing the inﬂ  uence of institutional racism in psychiatric diagnosis,

ing the inﬂ  uence of institutional racism in psychiatric diagnosis, 
referral, and treatment. Leading examples are the overdiagnosis of African-Americans and African-Caribbean Britons with schizo-phrenia, the tendency to perceive them as more dangerous and less amenable to psychotherapy, and differences in the way their dis-charge and aftercare are organized. Anthropologists have examined how racism is unwittingly built into psychiatric categories and inﬁ ltrates the model cases used to illustrate diagnostic criteria, and 
also the way that psychiatrists are trained to replicate such patterns in the practice of triage.
Cultural critique, informed by the cross-cultural and international

Cultural critique, informed by the cross-cultural and international 
data, is the basis for anthropologists’ doubts about the validity of many of the psychiatric conditions detailed in DSM-IV and ICD-10. The ethnographic database strongly suggests that, apart from brain tumours and infections, Alzheimer’s disease, metabolic encepha-lopathy, substance abuse, and other well-documented brain-based disorders such as certain sleep disorders, only six psychiatric syndromes of adults can be found cross-culturally; i.e. only these have stability as syndromes outside the cultural mainstream of Euro-American societies. The conditions are schizophrenia, brief

277
reactive psychoses, major depression, bipolar disease, a range of 
anxiety disorders from panic states through phobias to obsessive–compulsive disorder, and trauma, whether understood as PTSD or in other categories. Most of the other hundreds of conditions described in DSM-IV , for example, are culture bound to Euro-America.
Related to these contributions of cultural critique, anthropolo-
gists have also contributed to the development of culturally informed diagnostic criteria, questionnaires, structured inter-views, and guidelines for working with translators. Globalizing and indigenizing psychiatric approaches is an even more general emphasis in anthropology. Anthropology contains numerous con-cepts and methods that might be tried out, but relatively few have been experimented with or adopted. Besides those described below, several examples of the concepts, methods, and ﬁ  ndings 
from anthropology that await trial in psychiatry are listed in Table 2.6.2.1.

Local moral worlds: interpersonal basis of 
illness experience
Ethnographies—hundreds of them, including many on psychiat-

ric topics—demonstrate, with great consistency, that most people and most patients are not isolated individuals but rather live their lives as active members of local worlds. By local worlds, ethnogra-phers mean villages, neighbourhoods, networks, and families, as well as particular social institutions, including hospitals and out-patient systems. These local worlds are differentiated by class, ethnicity, gender, age cohort, political faction, religious ties, and still other social differences. In any given local world crucial things are at stake that orient the attention and actions of partici-pants. What is at stake may be shared (status, resources, survival, transcendence), but it also can be as distinctive as the different meanings of ultimacy that make religions distinguishable from 
each other.
Illness experience and experiences of treatment are as much

Illness experience and experiences of treatment are as much 
caught up these stakes as experiences of normality. Thus, for anthropology how a person’s illness is encountered, coped with, understood, and lived is crucial for understanding the illness and the treatment. Therefore, anthropologists write about the social course of illness: meaning that local worlds shape the course of ill-ness so thoroughly that the same disease process (diabetes, AIDS, depression, schizophrenia) can take different trajectories. When sick people go for treatment, who they ﬁ  rst seek out, whether they 
comply with the therapeutic regime, how they assess their experi-ence of treatment—all are in one way or another inﬂ  uenced by 
what is most at stake for communities, families, networks, and individuals. The anthropological contribution here is to highlight the processes through which individuals relate to collectives. Thus, Estroff
(2) shows that collective and individual deﬁ  nitions of iden-

tity affect how schizophrenic patients live their schizophrenia as an illness identity, which in turn affects their careers as patients and their experiences in other domains (family, workplace, etc.).
Practical clinical relevance
Immigration processes have so altered national demographic patterns that most nation states today have plural populations representing distinctive ethnic backgrounds. In 1900, the popula-tion of the United States, for example, included only 13 per cent categorized as ethnic minority members. By 1990 that ﬁ  gure was 
greater than 25 per cent. The perce ntage is projected to be one-third 
in 2010, and by mid-century to reach an astonishing 50 per cent. In California, the largest American state, non-Hispanic white Americans are already in a minority.
Ethnic background has been shown empirically to inﬂ  uence

Ethnic background has been shown empirically to inﬂ  uence 
epidemiological rates of disease, patterns of access to healthcare, help-seeking, and patient–doctor interactions, often with negative outcomes such as delayed treatment, misdiagnosis, non-compliance, and treatment failure. Taking ethnicity into account in 
the provision of services means a variety of things, such as making 
translators available, putting up signs in several languages, holding clinics at times when working-class patients can attend, and paying attention to differences in cultural meanings and practices. The now popular idea of providing culturally informed and sensitive care is premised on anthropological concepts and methods. Several of these have been elaborated in the literature.
1 The distinctions between illness and disease: for medical anthro-

pologists illness is the patient’s experience of symptoms in the context of family, work, and community; disease is the practi-tioner’s model of the pathological process. Help-seeking is usu-ally orientated around the illness experience with respect to what is most at stake for the patient and signiﬁ  cant others. Care 
can founder when the patient’s primary concerns with the ill-ness experience conﬂ  icts with or is entirely different from the

can founder when the patient’s primary concerns with the ill-ness experience conﬂ  icts with or is entirely different from the 
physician’s focus on disease. Thus, many patients with chronic pain experience interrogation of the disease process by the scep-tical physician as delegitimizing their illness experience. This leads to high rates of dissatisfaction with care among this group of patients. When patients and families are from ethnic minor-ity backgrounds, differences in cultural meanings and practices intensify conﬂ  icts between patient and physician models.Table 2.6.2.1 Anthropological concepts, methods, and ﬁ  ndings that 
await trial in psychiatry
Ethnography
Ethnography as a research strategy in clinical and epidemiological research.
For example, as a means of studying the clustering of psychiatric conditions 
with social problems. Ethnography also has uses in evaluation research,

with social problems. Ethnography also has uses in evaluation research, 
in generating categories and questions in epidemiological studies, and in sociosomatic research. It is also a means of training researchers.
Ethnographic database
Ethnographic database as a routine source of knowledge about communities 
(foreign and domestic) for clinicians, mental health planners, and researchers.
Cross-cultural comparisons
Cross-cultural comparisons as a routine form of knowledge production. 
For example, cross-cultural comparisons of psychotherapy might help (a) to clarify what is common among religious, moral, and medical healing, 
(b) to determine how culture inﬂ  uences psychotherapeutic practice, and 
(c)  to develop psychotherapeutic techniques for use with patients and families 
from different minority, ethnic, and international populations.
Social theory

Systematic reading of social theory as a source of hypotheses for research in 
social psychiatry and as a means of preparing clinicians to practise community 
psychiatry. Concepts such as social and symbolic capital, globalization, 
marginalization. ethnic identity, and institutional racism, among many others, can be used to frame psychiatric research and clinical intervention.2.6.2 social and cultural anthropology: salience for psychiatry

SECTION 2  the scientific basis of psychiatric aetiology 278
2 Medical anthropology sponsors a method to reduce this explan-
atory gap and thereby to improve clinical relationships. Called the explanatory models’ methodology, it involves three steps.
(3)
(a) E licitation of patient and family explanatory models of 
the illness experience and treatment, which can be accom-plished by asking the following questions:
◆ What do you call your problem?
◆ What do you think caused it?
◆ Why did it start when it did?
◆ What course will it take from here on?
◆ How does it work in your body?
◆ What do you most fear about the illness?
◆ What kind of treatment do you desire for this illness?
◆ What do you most fear about the treatment?
(b) Prese ntation of the clinician’s explanatory model of the 
disease process.
(c) Negotiation of a mutually acceptable unders tanding of 
the clinical problem across patient, family, and physician models.

Closely related to this technique is the development of a mini-
ethnography. This is a brief description, based on interviewing the key parties about the impact of family and work context on the ill-ness experience and vice versa. The mini-ethnography and the explanatory models’ elicitation generally give rise to patient stories of the illness experience. The inﬂ  uence of cultural categories, val-
ues and practices on the illness and treatment can be assessed from this standpoint.
(4)
Revised cultural formulation
Appendix I to DSM-IV contains an outline of how psychiatric cases can be culturally formulated. This has recently been updated
(6) and 
includes:
◆ the ethnic identity of the individual
◆ what is at stake as patients and their loved ones face an episode 
of illness
◆ the illness narrative
◆ psychosocial stresses and social supports

includes:
of illness
◆ cultural elements of the relationship between the individual and 
the clinician
◆ an examination of the efﬁ  cacy of a cultural competency approach 
in the particular case
This is a feasible approach to routine patient care with members 
of ethnic minorities and recent immigrants and refugees that has a high likelihood of making that care culturally informed and cultur-ally sensitive. Key to it, as it is to anthropology’s core methodology, ethnography, is the display of genuine respect for patients, families, and their meanings and practices. That respect for the person and his or her illness experience is the indispensable condition of anthropologically informed care. It includes, as its ﬁ  rst step, the

ethical act of acknowledging the suffering of the other in his or her own terms as the basis for diagnosis and treatment. In this sense, it 
reverses the cultural preoccupation of the biomedical practitioner with the disease process, and establishes the interpersonal relation-
ship as the grounds of knowledge as well as caregiving.
Anthropology’s chief contribution to psychiatry is to emphasize the importance of the social world in diagnosis, prognosis, and treatment, and to provide concepts and methods that psychiatrists can apply (the appropriate cross-disciplinary translation ﬁ  rst being

made, however). But that is not the only contribution that anthro-pology offers. Ethnographers are aware that knowledge is positioned, facts and values are inseparable, and experience is simply too com-plex and robust to be easily boxed into tight analytical categories. Hence a sense of the fallibility of understanding, the limitation of practice, and irony and paradox in human conditions is the conse-quence of ethnography as a method of knowledge production.
Anthropology also complements the idea of psychosomatic 
relationships with evidence and theorizing about sociosomatic relationships. Here moral processes—namely what is at stake in 
local worlds—are shown to be closely linked with emotional pro-

cesses, which are frequently about experiences of loss, fear, vexation, and betrayal of what is collectively and individually at stake in interpersonal relationships. Change in the former can change the latter, and this can at times work in reverse as well. Examples include the way symptoms intensify or even arise in response to fear and vexation concerning threats perceived as serious dangers to what is most at stake.
The relationship of poverty to morbidity and mortality is a

The relationship of poverty to morbidity and mortality is a 
different example of sociosomatic processes. Poverty correlates with increased morbidity and mortality. Psychiatrists have often had trouble getting the point that public health and infectious disease experts have long understood. But it is not just diarrhoeal disease, tuberculosis, AIDS, heart disease, and cancer that demon-strate this powerful social epidemiological correlation—so do psychiatric conditions. Depression, substance abuse, violence, and their traumatic consequences not only occur at higher rates in the poorest local worlds, but also cluster together (much as do infectious diseases), and those vicious clusters deﬁ  ne a local place, 
usually a disintegrating inner-city community. Hence the ﬁ  ndings

usually a disintegrating inner-city community. Hence the ﬁ  ndings 
of the National Co-Morbidity Study in the United States of America that most psychiatric conditions occur as comorbidity is a step toward this ethnographic knowledge—that in the most vulnerable, dangerous, and broken local worlds, psychiatric diseases are not encountered as separate problems but as part of these sociosomatic clusters.
Finally, anthropology is also salient for policy and programme 
development in psychiatry. Against an overly narrow neurobiological
framing of psychiatric conditions as brain disorders, anthropology in psychiatry draws on cross-national, cross-ethnic, and disinte-grating community data to emphasize the relationship of increas-ing rates of mental health problems, especially among underserved, 
impoverished populations worldwide, and increasing problems in

impoverished populations worldwide, and increasing problems in 
the organization and delivery of mental health services to funda-mental transformations in political economy, institutions, and culture that are remaking our epoch. In so doing, anthropology projects a vision of psychiatry as a discipline central to social welfare and health policy. It argues as well against the profession’s ethnocentrism and for the ﬁ  eld as a larger component of interna-
tional health. Anthropology (together with economics, sociology,

279
and political science) also provides the tools for psychiatry to 
develop policies and programmes that address the close ties between social conditions and mental health conditions, and social policies and mental health policies.
(5) In this sense, anthropology 
urges psychiatry in a global direction, one in which psychiatric 
knowledge and practice, once altered to ﬁ  t in more culturally salient 
ways in local worlds around the globe, have a more important place at the policy table.
(6,7)
Jenkins, J. and Barrett, R. (eds.) (2004). Schizophrenia, culture, and 
subjectivity: the edge of experience . Cambridge University Press, 
Kleinman, A. and Good, B. (eds.) (1985). Culture and depression . University 
of California Press, Berkeley, CA.
Kleinman, A. (ed.) (2006). What really matters: living a moral life amidst 
uncertainty and danger.  Oxford Press, Oxford.
Luhrmann, T. (2000). Of two minds: the growing disorder in American

Luhrmann, T. (2000). Of two minds: the growing disorder in American 
psychiatry.  Knopf, New Y ork.References
 1. Kleinman, A. (1977). Depression, somatization and the new 
cross-cultural psychiatry. Social Science and Medicine ,11, 3–10.
 2. Estroff, S.E. (1993). Disability and schizophrenia. In Knowledge, 
power and practice: the anthropology of medicine and everyday life(eds. S. Lindenbaum and M. Lock), pp. 247–86. University of California Press, Berkeley, CA.
 3. Kleinman, A. (1988). The illness narratives . Basic Books, New Y ork.
 4. Kleinman, A. (1988). Rethinking psychiatry: from cultural category to 
personal experience.  Free Press, New Y ork.
 5. Lee, S. and Kleinman, A. (1997). Mental illness and social change in 
China. Harvard Review of Psychiatry ,5, 43–5.
 6. Kleinman, A. and Benson, P . (2006). Anthropology in the clinic:

5. Lee, S. and Kleinman, A. (1997). Mental illness and social change in 
 6. Kleinman, A. and Benson, P . (2006). Anthropology in the clinic: 
The problem of cultural competency and how to ﬁ  x it. PLoS Medicine ,
3, e294. www.plosmedicine.org.
 7. Desjarlais, R., Eisenberg, L., Good, B., et al. (ed.) (1995). World 
mental health: problems and priorities in low-income countries . Oxford 
University Press, New Y ork.2.6.2 social and cultural anthropology: salience for psychiatry

2.7
of epidemiology to psychiatric aetiology
Scott Henderson
Epidemiology deals with the overall patterns of disease. On one 
hand, people are unique with their own genetic endowment and life experiences. This idiographic paradigm is balanced by the nomothetic in which recurrent and predictable patterns are sought in the whole of humankind. It is the business of psychiatric epide-miology to determine the distribution of mental disorders in pop-ulations, the factors determining that distribution, and measures that may help in their prevention.
From their undergraduate years onward, clinicians see patients 
who have a disorder and who at the same time give a history of certain experiences from birth to their present. It may be tempting for both patient and doctor to accept that the patient’s recent expe-riences have some role in the onset of symptoms. But if the princi-ples of epidemiology are brought into play, some questions need

to be asked ﬁ  rst. Being unwell may itself bias the recall of recent or 
distant experiences. What proportion of the general population have had the same experiences but not developed the disorder? What proportions have the same disorder but have not had these experiences? What proportions have the same disorder but have not reached health services? A simple two-by-two table is the sim plest
way to think this through (Table 2.7.1).
The columns are made up of persons in a population who have 
or do not have a particular disorder. The rows are the numbers who have or have not had a certain exposure. That exposure is being considered as a putative risk factor. It may be biological or psychosocial and may have taken place at any time from conception 
to the present.T o establish a causal link between some factor and a disorder 
is a demanding but most engaging exercise. It is well worth reading the classic expositions by Hill
(1) and Susser(2) on how a cause can

(1) and Susser(2) on how a cause can 
reasonably be inferred from the data.
The uses of epidemiology
In his celebrated monograph bearing this title, Morris(3) described 
seven uses of epidemiology. It continues to give us a framework for assessing the state of psychiatric epidemiology in relation to the biological and psychosocial conditions of the contemporary world. Morris’s list can be reinterpreted for our use as follows.
Completing the clinical picture
This means knowing about all the ways in which a disorder may present and what its usual course is. But it also means relating sub-clinical cases to fully developed ones. An excellent example here would be the anxiety, depressive, or somatization states seen in general practice or ﬁ  eld surveys compared to the more severe syn-
dromes speciﬁ  ed in the international criteria and encountered by 
psychiatrists.
Community diagnosis

Here one obtains estimates of morbidity as it occurs at the general population level, not just in persons who have reached primary care or mental health services. Only by having such estimates of prevalence or incidence for whole populations can the size of the nation’s disease burden be determined. This is because community-based measures of morbidity include not only persons with treated conditions but also those who are symptomatic yet have not reached services.
Secular changes in incidence
This refers to the rise and fall of diseases in populations. For exam-ple, there is some evidence that schizophrenia has been dropping in incidence and becoming more benign in its clinical course; and it is likely that in many Western countries, depressive disorder has become more frequent in persons born since the Second World Table 2.7.1  Cases and exposure: a two-by-two table
 Case
Yes No

Case
Yes No
Exposed Yes ab
No cd
Letters refer to numbers of persons.

281
War.(4) The suicide rate of young persons has indisputably increased 
in many industrialized countries. It is likely that eating disorders 
have increased in frequency and it is certain that the use of illegal 
drugs and AIDS are new arrivals and will be a continuing burden.
The search for causes
Here, epidemiology is looking for aetiological clues. It is the 
substance of this chapter.
Applying population data to individual risk
In this, the focus moves from the population back to the individual. 
For example, if the annual incidence rate for schizophrenia is 
known in a population and if this information is age-speciﬁ  c, it is 
possible to estimate the probability that a person in a given age 
group will develop the disorder within the next year. This is the 
base rate, before one starts to consider risk factors such as family 
history. Next, by aggregating data on the course of schizophrenia, it 
is possible to estimate the chances of recovery for persons who are

is possible to estimate the chances of recovery for persons who are 
currently having their ﬁ  rst episode. The common principle is that 
data based on large numbers of persons are used to make probability 
estimates for individuals.
Delineation of syndromes
This is done by examining the distribution of clinical phenomena 
as they occur in the population. It ﬁ  ts well with recent experience 
of repetitive strain injury, chronic fatigue syndrome, and post-
traumatic stress disorder or its congeners.
Health services research
This begins with a determination of needs and of resources, then 
an analysis of services currently in action, and ends with attempts 
to evaluate them, including the costs. Research activity in this 
area has expanded greatly in recent years, driven by the forces of 
economic rationalism.
Prevention
T o Morris’s seven uses of epidemiology should be added preven-

tion, which Gruenberg(5) said was its ‘ultimate service’ . All other 
uses are subsidiary to this. Examples are the current activity in the 
prevention of suicide in young persons and of alcohol or drug abuse. In these, the traditional medical approach of targeting 
high-risk groups should be contrasted with the epidemiological 
and population-based approach described by Rose.(6) One under-
recognized fact is that knowledge about factors that determine 
the duration of a disorder can lead to prevention. This is because 
prevalence is the incidence rate times the duration. So shortening 
the duration will lower the prevalence. For example, if people with 
depressive disorder were treated earlier in primary care, the pre-
valence should fall. The prevention of a mental disorder is greatly

valence should fall. The prevention of a mental disorder is greatly 
helped by knowledge about aetiology, but it is not essential. 
For example, Snow did not know about the cholera vibrio when 
he had the water supply changed. Prevention is discussed further 
by Bertolotte in Chapter 7.4, prevention in child psychiatry by 
Lenroot in Chapter 9.1.4, and in intellectual disability by Kaski in 
Chapter 10.3.
Research on aetiology: three levels
Epidemiological methods can be applied at any of the three levels: 
to disorders as these present in hospitals and specialist health 
services, in primary care, or in the general population. These are 
represented diagrammatically in Fig. 2.7.1 as a three-dimensional 
cone, derived from the seminal volume on pathways to care by 
Goldberg and Huxley.(7) The base of the cone consists of those 
in the general population who have clinically signiﬁ  cant psycho-

logical symptoms (Stage 1). When these symptoms become 
unmanageable to self or to others, people seek help from their 
doctor or other health practitioners (Stage 2). But only some of 
them are recognized by the professional to have signiﬁ  cant mental 
health problems (Stage 3). A small proportion may be referred to 
mental health services (Stage 4), of whom an even smaller fraction 
are admitted to inpatient care (Stage 5). Note that most teaching 
and the diagnostic criteria in international use are largely based on 
their authors’ experience in Stages 4 and 5, where patients are more 
severely ill!
There are two very different ways to express morbidity. The most 
common, and easiest to obtain, is prevalence, either at the time 
of assessment (point prevalence), 1-month, 1-year, or lifetime

of assessment (point prevalence), 1-month, 1-year, or lifetime 
prevalence. The other is incidence, the number of new or fresh 
onset cases in a given period. For aetiological research, incident 
cases are emphatically preferable.
Fig. 2.7.1 Pathways to care. (Reproduced from D.P . Goldberg and P . Huxley, Mental illness in the community, Copyright © 1980, The Tavistock Institute. )
2.7 the contribution of epidemiology to psychiatric aetiology

SECTION 2  the scientific basis of psychiatric aetiology 282
Three main designs
At any of these levels, research directed at aetiology uses one of 
three designs: cross-sectional, prospective longitudinal, or case-control. A cross-sectional study is often an excellent start, because it provides a picture of how much morbidity is present at one point in time and the variables most closely associated with this. But because it is only a ‘snapshot’ , the cross-sectional study can rarely allow much to be said about causes. For example, in a community sample of several thousand adults, the data will show that persons 
with symptoms of anxiety or depression will tend to report having

with symptoms of anxiety or depression will tend to report having 
had more adversities. But it would be unwise to conclude that adversity contributes to the onset of symptoms. First, persons with anxiety or depression may be more inclined to report that they have had many troubles. This may be through selective recall of unpleasant events, because it is known that depressed people are more likely to remember bad times than good times.
(8) Another 
mechanism is effort after meaning, whereby people try to account for feeling psychologically unwell. Next, symptomatic persons may be more likely to have unpleasant things happen to them as a con-sequence of their mental state. Lastly, persons with anxiety or depression may have certain personality traits or lifestyles that make them more likely to have troubled lives and also be vulnera-ble to common mental disorders.
Such problems in methodology can be resolved to some extent

Such problems in methodology can be resolved to some extent 
by using a prospective longitudinal design  or cohort study. In this, a 
population sample is assessed at the start when most persons are psychologically well. In one type of cohort study, the sample may deliberately include a group who have had a particular exposure, such as a head injury or disaster, and an equivalent number who 
have not. At the start, data are obtained on personality, lifestyle,

have not. At the start, data are obtained on personality, lifestyle, 
past health, and family history. The cohort is then re-examined at least once after an appropriate interval. Some will have developed symptoms. The research question is whether the putative risk factors that were assessed at the start were more frequently present in those who later developed symptoms. A design of this type yields consid-erably more information about the causal processes likely to be at work, either those leading to mental disorders or protecting against them. It also overcomes the problem of a putative risk factor really being a consequence rather than an antecedent of a disorder. But it is obviously very demanding in resources—human, administrative, and ﬁ  nancial. It also takes a long time. For these reasons, epidemi-
ologists often use the case-control  method as a more practicable 
alternative.
Case-control designs have been underused in psychiatric

Case-control designs have been underused in psychiatric 
research, but they can be a powerful strategy for identifying risk factors for a speciﬁ  ed disorder.
(9,10)  The essence of the case-control 
design lies in obtaining data to complete the cells in Table 2.7.1. The aim is to ﬁ  nd a sample of all persons in a population who have

reached case level for a particular disorder and an equivalent num-ber of persons who are similar in age, gender, and other variables, but who do not have the disorder, at least not yet. The cases should ideally be ‘incident’ or recent in onset. If instead, the study has to have recourse to all the cases of the disorder known to the service, that is, the prevalent cases, some will be long-standing and some more recent. This could lead to misleading results because a puta-tive risk factor may show up as ‘positive’ not because it is a cause or true risk factor, but because it is associated with chronicity through prolonging the duration of the disorder. This problem can be avoided only by recruiting recent-onset or incident cases for case-control studies. The cases and controls are then asked about the various possible exposures. If the cases are unable to give informa-tion because they are cognitively impaired (as in dementia), at least one informant has to be found for each case,

asked about the various possible exposures. If the cases are unable to give informa-tion because they are cognitively impaired (as in dementia), at least one informant has to be found for each case, usually a partner or close family member.

In Table 2.7.1, the important question is whether there are more 
persons in cell a than would occur by chance. We do not know the 
incidence of the disorder in all persons in the population who were exposed to each risk factor, nor do we know the number not exposed. Likewise, we do not know how many people in the popu-lation have recently developed the disorder. As a consequence, we cannot compare the incidence in those exposed and not exposed for the whole population. All we have are the data from the cases examined, who are necessarily only a fraction of all incident cases in the population; and data from a fraction of all healthy persons. But we can proceed as follows. First, the relative risk is calculated from Table 2.7.1. The relative risk is a/(a + b)   divided by 
c/(c + d)
i.e.a/(a + b )
   c/ (c + d )
By simple algebra, this becomesa(c + d )
c(a + b )
Then something very helpful can be done. Where a disorder is

c/(c + d)
   c/ (c + d )
c(a + b )
Then something very helpful can be done. Where a disorder is 
fairly uncommon in the general population, a will be very small 
compared with b, and c will be small compared with d. If we assume 
a negligible contribution by a in the term a + b, and by c in the 
term c + d, the relative risk will be nearly equal to
ad
bc
This is the odds ratio, which is an expression of the strength of a 
risk factor.
Whom to study: principles of sampling
The essential principle is that everyone in the true denominator (usually the total population within a defined geographical or administrative area) must have an equal probability  of being

The essential principle is that everyone in the true denominator (usually the total population within a defined geographical or administrative area) must have an equal probability  of being 
included in the numerator. If this is not achieved, there is a likeli-hood of bias whereby the achieved sample may be systematically different in ways that could be important in the analysis. For exam-ple, the sample of cases should not differ from all the incident cases in that population in attributes such as level of education, age, or likelihood of having been exposed to a candidate exposure or risk factor. So in a study of the association between, say, sexual abuse in childhood and depressive disorder in adult life, the cases of depres-sion should ideally be representative of all those with depressive disorder in that community and not just those reaching a particu-lar service. See also Chapter 2.2 by Dunn.
Sample bias
In ﬁ eld surveys, it has long been accepted that not everyone who

In ﬁ eld surveys, it has long been accepted that not everyone who 
is in the ‘target sample’ will agree to be interviewed or will be available at the time the interviewer calls. It is common to ﬁ  nd that

283
only 70 to 90 per cent are actually assessed. Furthermore, those 
who refuse or are repeatedly not available are known to be more likely to have the mental disorder under investigation. For this reason, the prevalence that is found will often be an underestimate. A putative risk factor may itself increase the chances of a person’s not being in a sample in the ﬁ  rst place, of dropping out, or of dying 
during the study. Statistical methods are available for estimating how much error may have occurred due to refusals and how to correct for this in the conclusions drawn.
The other occasion when non-response is a problem is in longi-

tudinal studies, where a sample is followed over several years. If a disorder with an increased mortality is the topic, such as dementia or schizophrenia, it is recognized that some cases will be lost at follow-up. This means that those who are successfully re-exam-ined are a survival élite and are different in important ways from the original cohort. These distortions could lead to mistaken conclusions if the losses are not allowed for. Various techniques have been developed to handle these difficulties, including Bayesian methods which adjust ﬁ  nal estimates on the basis of 
prior knowledge.
(11)
Specifying the disorders
Diagnostic categories

(11)
The epidemiology of mental disorders could have made no real progress without methods for specifying the disorders to be inves-tigated, then measuring these. Only in this way can research data be comparable between research teams, within and between countries. Having consistency in diagnosis has been made much easier through the development of the diagnostic criteria now in wide international use. The two systems are the International Classification of Diseases (10th Revision) ( ICD-10 ) with its 
Classification of Mental and Behavioural Disorders ; and the 
Diagnostic and Statistical Manual , fourth edition ( DSM-IV ) of the 
American Psychiatric Association. These classifications are described further in Chapter 1.9. Both are under revision.
Continuous measures of morbidity
Reliable and valid case ascertainment might be assumed to be the sine qua non  for any progress in the epidemiology of mental disor-

ders. But to use the traditional expression ‘case ascertainment’ nicely illustrates the very problem that has to be re-thought, because it implies a categorical structure in the morbidity that we wish to study. In a population, there are traditionally cases and non-cases. But this is not really how morbidity shows itself. As expressed by Pickering,
(12) ‘Medicine in its present state can count up to two, but 
not beyond’ . He was referring to hypertension, but others have 
argued that mental disorders also have dimensional properties.(6)
The frequency distribution of their component symptoms such as

The frequency distribution of their component symptoms such as 
anxiety, depression, or cognitive impairment is usually a reversed J-shape, with most people having none or only a few symptoms and progressively fewer persons having higher counts. A committee of clinicians in Geneva or Washington, whose experience is largely derived from teaching hospitals, has decided by consensus where the cut-point should be placed for persons to be ‘cases’ . While this is entirely appropriate for some purposes, it may not always be a true representation of the underlying pathology. In statistical terms, it loses information.It is not disputed that mental disorders exist in categorical states

and that these have some utilitarian value: a depressive episode, Alzheimer’s disease, anorexia nervosa, or alcohol dependency are clinically realistic entities. What is proposed here is that, in epide-miological studies at the general population level, hypotheses about the aetiology require large numbers of respondents, solely because the base rates for such conditions are not large. But it is possible to identify persons with some  symptoms of depression, of cognitive 
impairment, of abnormal eating, or of alcohol misuse. The score 
on a scale of these symptoms can become the dependent variable in an analysis of candidate risk factors. So it is usually more powerful statistically to look for associations between a putative risk factor and morbidity expressed as a continuous variable, rather than as a dichotomy of cases and non-cases.
When a continuous measure of common psychological symp-
toms such as the General Health Questionnaire ( GHQ )
(13) (vide

(13) (vide 
infra ) is applied to a population, a unimodal distribution curve is 
found, with no break between so-called cases and normals. Rose(6)
argued that there are three important consequences from this approach to studying morbidity. First, a characteristic of the community as a whole emerges. This is the mean and standard deviation of its GHQ scores. Second, this collective characteristic may show significant differences between men and women, geographical regions, social strata, and income groups. These dif-ferences are based on shifts of the entire distribution. The third consequence is that differences between these groups in the preva-lence of probable cases (those with a score above a threshold) are related to different average scores in these groups. As Rose
(6)

(6)
concisely put it, ‘The visible part of the iceberg (prevalence) is a function of its total mass (the population average)’ .
He suggested that ‘ Psychiatrists, unlike sociologists, seem generally 
unaware of the existence and importance of mental health attributes of whole populations, their concern being only with sick individuals ’
(emphasis added). It is an appealing notion that populations, while they are made up of individuals, take on properties of their own, much as molecules acquire attributes not found in their constitu-ent atoms. The concept of populations having different frequency distributions of dimensional morbidity, not just different preva-lence rates for clinical cases, carries with it the implication that some factors are shifting the overall distribution in some popula-tions but not in others. An example is the societal forces that 
Durkheim
(14) proposed were related to national suicide rates.
Disablement

Durkheim
There is yet a further advantage in considering morbidity as a con-

tinuum in a population. Morbidity refers to symptoms, syndromes, or disorders. But there is a universe of discourse closely linked to this, namely disablement. This is the collective noun now used to refer to the impairment, disability, and social role handicap in daily life that disorders bring with them. The main categories of mental disorder, especially the psychoses, affective disorders, and demen-tias, are almost always associated with substantial disablement. But subclinical levels of mental disorders also carry with them a certain amount of disablement. From the point of view of a whole popula-tion, the cumulative amount of disablement from subclinical or milder conditions is considerable because such conditions have a high point prevalence. Therefore, from a public health perspective, the signiﬁ  cance of milder mental disorders is not trivial.2.7 the contribution of epidemiology to psychiatric aetiology

SECTION 2  the scientific basis of psychiatric aetiology 284
Measurement of disablement
The most comprehensive measure is the Disability Assessment 
Schedule (DAS)(15) that assesses an individual’s functioning in 
daily life. Its short form is suitable for survey use. Self-completion instruments are the Brief Disability Questionnaire (BDQ)
(16) and 
the SF-36(17) or its briefer version, the SF-12.
The measurement of psychiatric symptoms
Instruments for epidemiological research fall into two types: self-completed questionnaires and standardized interviews.
Questionnaires
The more simple type is a symptom scale which can be completed by respondents themselves or administered by an interviewer. The best-known instrument is the GHQ. The briefest version, the GHQ-12, is a highly efﬁ  cient screening tool. A score of 2 or more 
indicates that the person is likely to have one of what Goldberg and Huxley
(18) have usefully termed common mental disorders.

(18) have usefully termed common mental disorders. 
Another screening instrument is the Hopkins Symptom Checklist.
(19) For depressive states speciﬁ  cally, examples are the 
Center for Epidemiologic Studies Depression Scale ( CES-D )(20)
and the Beck Depression Inventory.(21)
The Alcohol Use Disorders Identiﬁ  cation T est ( AUDIT ) was 
developed by the WHO for population screening. This 10-item test has been shown to have satisfactory psychometric and predictive properties. The total score is 40 and a score of 8 or more (7 for women) is recommended for identifying persons likely to have adverse consequences of drinking.
(22)
For cognitive impairment, the Mini-Mental State Examination 
(MMSE )(23) gives a score for a person’s current cognitive function,

(22)
(MMSE )(23) gives a score for a person’s current cognitive function, 
or by applying a cut-point to that score, it can be used to identify persons who are likely to have a dementia. Like any other cognitive test, it cannot itself make a diagnosis of dementia. It detects cogni-tive impairment, not cognitive decline, which requires a history. The MMSE is known to be sensitive to education, in that persons with limited intelligence or education may have low scores without their having had any cognitive decline.
All these instruments can be used in two ways: by applying a 
cut-point to identify persons who are likely to be clinically signiﬁ  -
cant cases; or by using the score as a continuous variable. When a questionnaire or self-rated instrument is used in research, the investigators have to be conﬁ  dent about its psychometric proper-
ties. In addition to validity and reliability, there are two others: its

ties. In addition to validity and reliability, there are two others: its 
sensitivity and speciﬁ  city. These refer to its performance when 
compared with a criterion or ‘gold standard’ , such as a comprehen-sive psychiatric examination or a consensus diagnosis amongst experts. In Table 2.7.2, a sample of persons has been examined with both the screening instrument and a full examination. We consider the number of persons who are ‘cases’ according to both assess-ments ( a), according to one but not the other ( b or c), and accord-
ing to neither ( d).
Sensitivity is the proportion who screen positive and who 
are indeed cases by the criterion; that is: a/(a + c), while speciﬁ  city 
is the number who screen negative and who are indeed not cases: 
d/(b + d).
The sensitivity and speciﬁ  city of a test are expressed as a percent-
age and vary according to where the cut-point is placed on the scores. As sensitivity increases, speciﬁ  city tends to decrease, so that an

age and vary according to where the cut-point is placed on the scores. As sensitivity increases, speciﬁ  city tends to decrease, so that an 
appropriate balance between the two has to be determined. For some purposes, such as in screening for depression, it is more 
important to identify as many as possible of the true cases, but it does not matter if there are quite a few false-positives because these 
can be corrected by a more extensive second-stage examination. Under these conditions, one would want a highly sensitive screen-ing test that placed most of the true cases in cell a and few in c.
It matters rather less if quite a few of the true non-cases are incor-rectly placed in b. See also Chapter 2.2 by Dunn.
Standardized psychiatric interviews
Even the best-designed questionnaires with the best psychometric

Even the best-designed questionnaires with the best psychometric 
properties cannot be a substitute for a psychiatric interview. Only it can obtain the information that leads to a diagnosis, reached according to the international criteria. What is termed information variance is reduced by having interviewers ask about symptoms in the same way. Next is the reduction of criterion variance, where the symptoms or signs elicited are, like building bricks, assembled in exactly the same way, both within and across studies. This is achieved by applying to the data an algorithm that is a precise expression of the diagnostic criteria in ICD or DSM. The algorithm can be computerized so that the responses to each item in the interview are assembled automatically and invariably.
There are two types of standardized psychiatric examination. 
The Schedule for Clinical Assessment in Neuropsychiatry ( SCAN )

is a clinician’s instrument, requiring familiarity with the phenom-enology of mental disorders. It assumes that interviewers are comfortable in examining persons with a mental disorder. The sec-ond type, exempliﬁ  ed by the Composite International Diagnostic 
Interview ( CIDI ) is fully scripted and has been automated for 
interviewing on laptop computers so that it can be administered by laypersons after only a few days’ training. A very large body of survey data has now been collected using it. These instruments are fully described by Cooper and Oates in Chapter 1.8.1.
Validity issues

The quality of information these instruments obtain is clearly of central importance. We know that they do not obtain the same information as each other, nor do they identify the same persons as cases of a particular diagnostic category in the same sample. Their validity and the practical signiﬁ  cance is therefore important for 
administrators using the data obtained in large surveys to guide planning. But it is also a matter of interest for aetiological research.Table 2.7.2  Screening a population sample
Criterion (cases by full psychiatric assessment)
Yes No
Cases by 
screening testYes a b a+b
No c d c+d
a+c b+d

285
Typical prevalence estimates
The above instruments have been used in a large number of sur-
veys of the prevalence of the main mental disorders in the general population. Examples are shown in Table 2.7.3. The rates vary markedly, but little is known about why this is so. The differences may be due to differences in methods of case ascertainment; or they may indicate actual variation between countries. What is important is that they all attempt  to estimate the prevalence in the 
community of syndromes familiar to psychiatrists working in clin-ics and hospitals. Prevalence estimates provide evidence for the public health signiﬁ  cance of mental illnesses and their associated 
disablement. Their administrative impact has been considerable. So far, however, they have brought little to advance knowledge about aetiology.
(a) Possible causes of mental disorders: the domains
Having speciﬁ  ed the psychiatric disorder to be studied and having

Having speciﬁ  ed the psychiatric disorder to be studied and having 
developed methods to measure it, the next task is to identify what-ever factors might contribute to its onset or to its course. These lie in the traditional three domains: the biological, social, and psycho-logical. But in epidemiology, any variable is rarely speciﬁ  c to one 
domain. Some biological, some social, and some psychological fac-tors are often conﬂ  ated. For example, gender expresses biological 
differences but also different social experiences in the past, differ-ent social contexts in the present, and different psychological or intrapersonal differences in personality traits and behaviour. Likewise, age groups can reﬂ  ect social role, educational opportuni-
ties in the past, marital status, ﬁ  nancial concerns, and physical

ties in the past, marital status, ﬁ  nancial concerns, and physical 
health. It is therefore important not to be misled into thinking that a variable is tapping only what one is primarily interested in. 
Confounding is ever present.
(b) Sociodemographic variables
The level of psychiatric morbidity in a population may differ 
signiﬁ  cantly between age groups, gender, marital status, ethnic background, and socio-economic or educational level. Depressive 
disorders are consistently more prevalent in women(24) and demen-
tia has a higher prevalence, not only with increasing age, but also in those with lower education.
(25) Furthermore, there may be 
important interaction effects between variables in their relation to 
morbidity. For example, the average age of onset in schizophrenia is different in men and in women. This has proved to be a clue to causal processes.
(c) The social environment
This can be considered in two parts: ﬁ  rst is the individual’s imme-

diate social environment—what the sociologist Cooley(26) called 
the primary group—consisting of those around a person with whom there is both interaction and commitment. There is then the wider community with its standard of living, lifestyle, and cultural values. Plausibly, both may have some inﬂ  uence on the incidence of 
mental disorders and on their course. The hypothesis that social support protects against depression and other common mental disorders has proved hard to investigate.
(27, 28) This is because

(27, 28) This is because 
social support is probably influenced by some intrapersonal factors rather than being a product solely of the individual’s environment. Here is a good example of confounding: a major variable concerning the social environment of individuals turns out to be determined not solely by environmental factors, but partly by their own personality attributes. The evidence suggests that social support, stripped of these confounding factors, is not a powerful factor in aetiology.
(29) A separate issue is whether social 
support inﬂ  uences the outcome of psychiatric disorders once these 
have developed.
Societal (macrosocial) variables have long been suspected of

Societal (macrosocial) variables have long been suspected of 
playing an important role in aetiology. It was such a hypothesis that was investigated in the celebrated Stirling County Study in Canada by Dorothea and Alexander Leighton et al .
(30) with their 
concept of sociocultural disintegration. The current increase in depression and suicide in the young is popularly attributed to such macrosocial variables. On the other hand, work opportuni-ties, diet and use of drugs and alcohol have also changed appre-ciably over the last 50 years. There is no certain explanation so far.
Experiential variables

‘Experiential’ is a useful term to refer inclusively to all that indi-viduals have been exposed to, from conception to death. In epide-miological research, it includes intrauterine exposures—such as maternal influenza or malnutrition—and perinatal events. In infancy and childhood, social and interpersonal experiences have been the main focus of research. Maternal deprivation was inten-sively studied in both clinical and community samples for two decades. The expectation from Bowlby’s attachment theory was that loss or separation from the mother would be pathogenic for depression and possibly personality disorders.
(31) This hypothesis 
has proved very hard to test because of confounding by other fac-tors. Rutter
(32) concluded that ‘ . . . the residual effects of early expe-

riences on adult behaviour tend to be quite slight because of both the maturational changes that take place during middle and later childhood and also the effects of beneﬁ  cial and adverse experiences 
during all the years after infancy . . . ’Table 2.7.3  Some 12-month prevalence rates per 100 of population, 
all by DSM-IV criteria
Any 
disorder* (%)Anxiety 
disorderMood 
disorderAlcohol or substance 
use disorder
Australia 20.3 5.6 6.6 7.9
Canada 10.9 5.2 5.8 _China (Beijing) 9.1 3.2 2.5 2.6Colombia 17.8 10.0 6.8 2.8European 
countries (six)9.6 6.4 4.2 1.0 (alcohol only)
Iran
†17.1 8.4 4.3 nil
Lebanon 16.9 11.2 6.6 1.3New Zealand 20.7 14.8 8.0 3.5Nigeria 4.7 3.3 0.8 0.8Ukraine 20.5 7.1 9.1 6.4USA 26.4 18.2 9.6 3.8
*Includes disorders other than those listed.

Iran
†Only lifetime estimates were published.2.7 the contribution of epidemiology to psychiatric aetiology

SECTION 2  the scientific basis of psychiatric aetiology 286
Migration and schizophrenia
Migration is an excellent example of how epidemiological data lead 
to aetiological clues, straddling both the biological and social. People who have moved from one country to another have offered opportunities for aetiological research on schizophrenia for a long time, starting with the celebrated study in 1932 by Ödegaard. He found that Norwegian migrants to Minnesota had more mental disorders than those at home. Since then, migration has become increasingly common and some striking ﬁ  ndings have been made. 
An integrative review
(33) has found a relative risk of 2.7 for ﬁ  rst-

generation migrants and 4.5 for the second-generation. While a family history is the largest risk factor for schizophrenia, migration is the next compared with most others. It is not due to an artefact in diagnosis. The effect is unlikely to be due to any single factor. Both biological and social factors are probably implicated. In the latter, perception of social inequality is thought to be a plausible mechanism.
Parental style
Promising ﬁ  ndings have been obtained on the association between 
parenting style and depressive disorders in adulthood. Parker(34)
developed the Parental Bonding Instrument ( PBI) to measure two

developed the Parental Bonding Instrument ( PBI) to measure two 
fundamental dimensions of the manner in which parents behave towards their children: care and affection as one dimension and protectiveness as the other. The PBI is too lengthy for epidemio-logical research on community samples where the interview is often already extensive. Parker and his colleagues have subse-quently developed a briefer instrument, the Measure of Parenting Style ( MOPS ), which includes the experience of physical and 
sexual abuse.
(35) MOPS is likely to prove useful in case-control and 
prospective studies of psychiatric disorders for systematically obtaining information on exposures of theoretical relevance.
(a) Childhood abuse

It seems intuitively likely that children who have been physically or sexually abused have an increased risk of having anxiety, depres-sion, or other psychiatric disorders in adulthood. The ﬁ  ndings 
from epidemiological studies on unreferred samples (people in the community) point to the many other adverse experiences that accompany childhood sexual abuse, including physical violence, unstable and untrustworthy relationships with parents, and emotional deprivation. This topic is further considered in Chapter 9.3.3.
(b) Recent exposure to adversity

Adverse experiences have been very extensively studied for their contribution to the onset and course of psychiatric disorders. In epidemiological research, much attention has been accorded to issues that arise in the measurement of adversity. Some of these issues are equally relevant in clinical practice. They include the following:
◆ The duration of the stressor: acute or long-standing.
◆ Its magnitude and how to determine this independently of the 
person’s reaction to it.
◆ The independence of the event from the individual: some events 
are entirely independent while others may have come about because of the individual’s own behaviour or psychiatric state.◆ The personal context of the experience may augment or reduce 
its psychological impact.
◆ Confounding by personality traits that may be independently 
associated with psychiatric morbidity.
◆ The additive effect of multiple events, some of which may be 
causally linked in a chain.

◆ The quality of the event itself: a loss or a threat.
◆ Effort after meaning, whereby patients and doctors may attribute 
symptoms to a particular experience as a way to explain the onset of illness.
These issues are fully discussed in Chapter 2.6.1.
Personality variables
Although personality traits may contribute to how vulnerable indi-
viduals are to adverse experiences, it has not often been possible to measure personality traits in general populations, then follow the sample prospectively to demonstrate if the incidence of speciﬁ  c 
disorders is indeed higher in some types. Many measures of per-sonality are too lengthy to be used in surveys. One exception is the Eysenck Personality Questionnaire ( EPQ-R ) in which the trait of

disorders is indeed higher in some types. Many measures of per-sonality are too lengthy to be used in surveys. One exception is the Eysenck Personality Questionnaire ( EPQ-R ) in which the trait of 
neuroticism has been found to confer increased risk of anxiety, depression or later schizophrenia.
(36) The assessment of personality 
is considered in Chapter 1.8.2.
Molecular genetics and epidemiology

In the next few years, it can be expected that some personality traits will be found to occur more often in people with particular alleles in genes related to brain function. Amongst these, a pre-ferred group of candidates are genes with known polymorphisms that alter the function of neurotransmitter systems, either by affecting the metabolism of a transmitter or some aspect of its function such as transport, receptor binding, or signal transduc-tion. The attraction for psychiatric epidemiology is twofold: the promise of introducing to population studies a biological variable of fundamental signiﬁ  cance; and the possibility of looking for 
interaction between biologically based vulnerability and life expe-riences. The ﬁ  nding by Caspi et al .
(37) sparked great interest by

(37) sparked great interest by 
reporting an association between a 5-HTT polymorphism and depression, but only on persons who had been exposed to recent adversity. The finding has not been consistently replicated. Furthermore, the relevant polymorphisms may be rather more complicated than at ﬁ  rst assumed. What is signiﬁ  cant is that it is 
now feasible to study genotype and environment at the popula-tion level.
How epidemiologists think
We can now look back on the strategies used to ﬁ  nd causes of men-
tal disorders and how epidemiologists go about the task. T o ﬁ  nd 
aetiological clues, they look ﬁ  rstly for associations, some of which 
may later be shown to have a causal inﬂ  uence. This is often best

may later be shown to have a causal inﬂ  uence. This is often best 
done by working not with individual patients, nor even with a series of patients in one clinic. Instead it is better to have data that represent all cases of a disorder in a deﬁ  ned population. The way in 
which a candidate risk factor comes to be proposed is itself very interesting. There are three:

287Table 2.7.4  The search for causes: a matrix for epidemiological studies
Child 
psychiatric 
disordersAnxiety 
disordersAffective 
disordersSchizophrenia Dementias Personality 
disordersEating 
disordersAlcohol and 
substance 
abuseSuicide Parasuicide Intellectual 
disabilityPsychological 
well being
Sociodemographic 
factorsGender
AgeMarital status
Social class
EducationEmployment status
Urban/rural
World region
Experiential 
factorsSeason of birth
Parental age
Childhood separation
Parental styleCultural or subcultural 
 beliefs and attitudes
Adverse experiencesExtreme experiences
Bereavement
Expressed emotion  (for relapse)
Social support
Secular changes in 
 society
Other macrosocial  factors (economic 
 depression, war, 
 social cohesion)
Migration
Climate and daylightNoise
Environmental toxins
DietAlcohol and drugs
Medication
Infections
Physical illness
Interaction of two or 
 more factorsComorbidity
Genetics: major genes 
     quantitative 
trait loci

trait loci
No attempt has been made to be exhaustive in either the classes of morbidity or the putative causal factors.2.7 the contribution of epidemiology to psychiatric aetiology

SECTION 2  the scientific basis of psychiatric aetiology 288
1 The inspired hypothesis . A sharp-eyed clinician develops the 
idea that some factor—in any of the three domains—is present more often than by chance in a certain disorder; and that factor may contribute to the onset of the disorder. This is exactly what happened to the ophthalmologist Sir Norman Gregg in Sydney when he noticed that many disabled children had mothers who had contracted rubella during the pregnancy. The association was later conﬁ  rmed and shown to be causal. So here a hypothesis 
arising in the course of clinical work was taken out of the clinic and tested by epidemiological methods, then the knowledge applied in prevention.
2 A coarse observation . A second pathway to a hypothesis starts

2 A coarse observation . A second pathway to a hypothesis starts 
with a coarse observation of a link between a disorder and, say, some demographic variable. Here are two examples. In the aeti-ology of schizophrenia, a slight excess in winter birthdates was noticed in persons who later developed schizophrenia. Work on the 1946 birth cohort in Britain showed that persons who later developed schizophrenia had been recorded as children to have had more speech and educational problems, more social anxiety, and a preference for solitary play. Both observations point to a neurodevelopmental hypothesis for schizophrenia.
3 The enquiry is theory driven . A good example is what came

3 The enquiry is theory driven . A good example is what came 
from attachment theory. In epidemiological research on Alzheimer’s disease, it was theory that led to a search for puta-tive risk factors such as a family history of Down syndrome, alu-minium in drinking water, maternal age at the patient’s birth, and a history of previous head injury. It was also theory that led Jenkinson et al . to find an inverse association between 
Alzheimer’s disease and rheumatoid arthritis. This subsequently led to studies of people who had been treated with long-term anti-inﬂ  ammatory drugs.
4 The search for causes: a matrix for epidemiological studies . All

4 The search for causes: a matrix for epidemiological studies . All 
these three approaches can be brought together, and then used as the building material to construct a matrix. This can then drive a systematic search. In Table 2.7.4, the main categories of mental disorders are listed across the top to form the columns, while the rows are made up of those variables that may contribute to the onset or course of morbidity. The matrix proves to be a tidy way of organizing what information is already available; but it also acts heuristically by proposing associations that call for investiga-
tion but might not otherwise have been considered. The variables 
can be placed in categories: sociodemographic, experiential, intrapersonal (psychological), and biological. The alert observer will notice that interactions between two or more variables should be considered, because these can be of the greatest importance.

The epidemiology of psychiatric disorders has shown the extent to which these are present in all human populations. It has also provided a large body of knowledge about aetiology. Now that biological including genetic information can be added to data on environmental exposures, opportunities for further advancement carry much promise.
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3.1 Psychoanalysis: Freud’s theories and their 
306
 3.3 Current psychodynamic approaches to psychiatry  313
Glen O. GabbardSECTION 3
Psychodynamic 

3.1
Psychoanalysis is:
1 A personality theory, and, more generally, a theory of psycho-
logical functioning that focuses particularly on unconscious mental processes;
2 A method for the investigation of psychological functions based 
on the exploration of free associations within a special therapeu-tic setting;
3 A method for treatment of a broad spectrum of psychopatho-
logical conditions, including the symptomatic neuroses (anxiety states, characterological depression, obsessive–compulsive disorder, conversion hysteria, and dissociative hysterical pathology), sexual inhibitions and perversions (‘paraphilias’), and the personality disorders.
Psychoanalysis has also been applied, mostly in modiﬁ  ed versions, 
i.e. in psychoanalytic psychotherapies, to the treatment of severe personality disorders, psychosomatic conditions, and certain psy-chotic conditions, particularly a subgroup of patients with chronic schizophrenic illness.

All three aspects of psychoanalysis were originally developed by 
Freud
(1–3) whose theories of the dynamic unconscious, personality 
development, personality structure, psychopathology, methodology of psychoanalytic investigation, and method of treatment still largely inﬂ  uence the ﬁ  eld, both in the sense that many of his central 
ideas continue as the basis of contemporary psychoanalytic think-ing, and in that corresponding divergencies, controversies, and radical innovations still can be better understood in the light of the overall frame of his contributions. Freud’s concepts of dream anal-ysis, mechanisms of defence, and transference have become central aspects of many contemporary psychotherapeutic procedures.
Freud’s ideas about personality development and psychopatholo-
gy, the method of psychoanalytic investigation, and the analytic

gy, the method of psychoanalytic investigation, and the analytic 
approach to treatment gradually changed in the course of his dra-matically creative lifespan. Moreover, the theory of the structure of the mind that he assumed must underlie the events that he observed clinically changed in major respects, so that an overall summary of his views can hardly be undertaken without tracing the history of his thinking. The present overview will lead up to summaries of his ﬁ nal conclusions as to the structure of the mind and how this is 
reflected in personality development and psychopathology. Psychoanalysis will then be described as a method of treatment, as seen from the point of view of resolution of conﬂ  ict between impulse 
and defence, and from that of object-relations theory. We shall explore signiﬁ  cant changes that have occurred in all these domains,

and defence, and from that of object-relations theory. We shall explore signiﬁ  cant changes that have occurred in all these domains, 
and conclude with an overview of contemporary psychoanalysis, with particular emphasis upon the presently converging tendencies of contemporary psychoanalytic approaches, and new developments that remain controversial.
Freud’s theory of the mental apparatus: 
motivation, structure, and functioning
Unconscious mental processes: the topographic 
theory; defence mechanisms
Freud’s starting point(4) was his study of hysterical patients and the 
discovery that, when he found a way to help these patients piece together a coherent account of the antecedents of their conversion symptoms, dissociative phenomena, and pathological affective dis-positions, all these psychopathological phenomena could be traced to traumatic experiences in their past that had become uncon-scious. That is, these traumatic experiences continued to inﬂ  uence

the patients’ functioning despite an active defensive mechanism of ‘repression’ that excluded them from the patient’s conscious awareness. In the course of a few years, Freud abandoned his early efforts to recover repressed material by means of hypnosis, and replaced hypnosis with the technique of ‘free association’ , an essen-tial aspect of psychoanalytic technique until the present time. Freud instructed his patients to eliminate as much as possible all 
‘prepared agendas’ , and to try to express whatever came to mind, 
while attempting to exert as little censorship over this material as they could. He provided them with a non-judgemental and stable setting in which to carry out their task, inviting them to recline on a couch while he sat behind it. The sessions lasted for an hour and were conducted ﬁ  ve to six times a week. There has been little

change in the essentials of this format, except that sessions have been shortened to 45 to 50 min and are carried out three to Psychoanalysis: Freud’s 
theories and their contemporary development

SECTION 3  psychodynamic contributions to psychiatry 294
ﬁ ve times a week. The method of free association led to the gradual 
recovery of repressed memories of traumatic events. Originally, Freud thought that the recovery of such events into consciousness would permit their abreaction and elaboration, and thus resolve the patients’ symptoms.
Practicing this method led Freud to several lines of discovery. 
T o begin, he conceptualized unconscious mechanisms of defence that opposed the recovery of memories by free association. He described these mechanisms, namely, repression, negation, isolation, 
projection, introjection, transformation into the opposite, rational-

ization, intellectualization, and most important, reaction formation. The last of these involves overt chronic patterns of thought and behaviour that serve to disguise and disavow opposite tendencies linked to unconscious traumatic events and the intrapsychic con-ﬂ icts derived from them. The discovery of reaction formations led 
Freud to the psychoanalytic study of character pathology and nor-mal character formation, and still constitutes an important aspect of the contemporary psychoanalytic understanding and treatment of personality disorders (for practical purposes, character pathology and personality disorders are synonymous concepts).
A related line of development in Freud’s theories was the discovery

of the differential characteristics of conscious and unconscious thinking. Freud differentiated conscious thinking, the ‘secondary process’ , invested by ‘attention cathexis’ and dominated by sensory perception and ordinary logic in relating to the psychosocial envi-ronment, from the ‘primary process’ of the ‘dynamic unconscious’ . That part of the unconscious mind he referred to as ‘dynamic’ exerted constant pressure or influence on conscious processes, against the active barrier constituted by the various defensive operations, particularly repression. The dynamic unconscious, Freud proposed, presented a general mobility of affective investments, and was ruled by the ‘pleasure principle’ in contrast to the ‘reality principle’ of consciousness. The ‘primary process’ thinking of the dynamic unconscious was characterized by the absence of the princi-ple of contradiction and of ordinary logical thinking, the absence of negation and of the ordinary sense of time and space, the treatment

unconscious was characterized by the absence of the princi-ple of contradiction and of ordinary logical thinking, the absence of negation and of the ordinary sense of time and space, the treatment of a part as if it were equivalent to the whole, and a general tendency towards condensation of thoughts and the displacement of affective investments from one to another mental content.

Finally, Freud proposed a ‘preconscious’ , an intermediate zone 
between the dynamic unconscious and consciousness. It represent-ed the storehouse for retrievable memories and knowledge and for affective investments in general, and it was the seat of daydreaming, in which the reality principle of consciousness was loosened, and derivatives of the dynamic unconscious might emerge. Free asso-ciation, in fact, primarily tapped the preconscious as well as the layer of unconscious defensive operations opposing the emergence of material from the dynamic unconscious.
This model of the mind as a ‘place’ with unconscious, precon-
scious, and conscious ‘regions’ constituted Freud’s
(1) ‘topographic 
theory’ . He eventually replaced it with the ‘structural theory’ namely, the concept of three interacting psychic structures, the ego, the super-ego, and the id.
(5) This tripartite structural theory is still the model of

(5) This tripartite structural theory is still the model of 
the mind that dominates psychoanalytic thinking. A major determi-nant of the shift from the topographic to the structural model was 
Freud’s recognition that the ‘regions’ of conscious, preconscious, and 
unconscious were ﬂ  uid, and that the defence mechanisms directed 
against the emergence in consciousness of the dynamic unconscious were themselves unconscious. Another consideration was Freud’s
(6)discovery of a specialized unconscious system of infantile morality, the superego. What follows is a summary of the characteristics and contents of these structures, an analysis that will lead us directly into contemporary psychoanalytic formulations.
The structural theory, the dual-drive theory, 
and the Oedipus complex
The id: infantile sexuality and the Oedipus complex
The id is the mental structure that contains the mental representa-
tives of the ‘drives’ , that is, the ultimate intrapsychic motivations that Freud

(7) described in his ﬁ  nal, ‘dual-drive theory’ of libido and 
aggression, or metaphorically, the sexual or life drive and the destruction or death drive to be examined below. Behind this categorical formulation lies a complex set of discoveries regarding the patients’ unconscious experiences that Freud came across in the course of the application of the psychoanalytic method to the treat-ment of neurotic and characterological symptoms. In exploring unconscious mental processes, what at ﬁ  rst appeared to be speciﬁ  c 
traumatic life experiences turned out to reﬂ  ect surprisingly consi-
stent, repetitive intrapsychic experiences of a sexual and aggressive nature.
Freud
(4) was particularly impressed by the regularity with which 
his patients reported the emergence of childhood memories reﬂ  ect-

ing seductive and traumatic sexual experiences on one hand, and intense sexual desires and related guilt feelings, on the other. He dis-covered a continuity between the earliest wishes for dependency and being taken care of (the psychology, as he saw it, of the baby at the mother’s breast) during what he described as the ‘oral phase’ of development; the pleasure in exercising control and struggles around autonomy in the subsequent ‘anal phase’ of development (the psy-chology of toilet training); and, particularly, the sexual desire towards the parent of the opposite gender and the ambivalent rivalry for that parent’s exclusive love with the parent of the same gender. He described this latter state as characteristic of the ‘infantile genital stage’ (from the third or fourth to the sixth year of life) and called its characteristic constellation of wishes and conﬂ  icts the positive

Oedipus complex. He differentiated it from the negative Oedipus complex, i.e. the love for the parent of the same gender, and the corresponding ambivalent rivalry with the parent of the other gender. Freud proposed that Oedipal wishes came to dominate the infantile hierarchy of oral and anal wishes, becoming the fundamen-tal unconscious realm of desire.
Powerful fears motivated the repression of awareness of infantile

Powerful fears motivated the repression of awareness of infantile 
desire: the fear of loss of the object, and later of the loss of the object’s love was the basic fear of the oral phase, directed against libidinal wishes to possess the breast; the fear of destructive control and annihilation of the self or the object was the dominant fear of the anal phase directed against libidinal wishes of anal expulsion and retentiveness, and the fear of castration, ‘castration anxiety’ , the dominant fear of the Oedipal phase of development, directed against libidinal desire of the Oedipal object. Unconscious guilt was a dominant later fear, originating in the superego and generally directed against drive gratiﬁ  cation (see under super-
ego). Unconscious guilt over sexual impulses unconsciously equated with Oedipal desires constitute a major source of many types of pathology, such as sexual inhibition and related character pathology.

295
Prototypical intrapsychic infantile expe riences linked to the Oedipus 
complex were fantasies and perceptions around the sexual intimacy of the parents (the ‘primal scene’), and unconscious fantasies derived from experiences with primary caregivers (‘primal seduction’). In all these phases of infantile development of drive motivated wishes and fears, powerful aggressive strivings accompanied the libidinal ones, such as cannibalistic impulses during the oral phase of physical dependency on the breast and psychological dependency on mother, sadistic fantasies linked to the anal phase, and parricidal wishes and 
phantasies in the Oedipal stage of development.
Freud described the oral phase as essentially coinciding with the

Freud described the oral phase as essentially coinciding with the 
infantile stage of breast feeding, the anal phase as coinciding with struggles around sphincter control, and the Oedipal stage as devel-oping gradually during the second and through the fourth years, and culminating in the fourth and the ﬁ  fth years of life. This latter 
phase would then be followed by more general repressive processes under the dominance of the installation of the superego, leading to a ‘latency phase’ roughly corresponding to the school years, and ﬁ  nally, 
to a transitory reactivation of all unconscious childhood conﬂ  icts 
under the dominance of Oedipal issues during puberty and early adolescence.
The id: drives

The drives represent for human behaviour what the instincts constitute for the animal kingdom, i.e. the ultimate biological motivational system. The drives are constant, highly individualized, developmentally shaped motivational systems. Under the domi-nance of the drives and guided by the primary process, the id exerts an ongoing pressure towards gratiﬁ  cation, operating in accordance 
with the pleasure principle. Freud initially equated the drives with primitive affects. After discarding various other models of uncon-scious motivation, he ended up with the dual-drive theory of libido and aggression.
He described the libido or the sexual drive as having an ‘origin’ in

He described the libido or the sexual drive as having an ‘origin’ in 
the erotogenic nature of the leading oral, anal, and genital bodily zones; an ‘impulse’ expressing the quantitative intensity of the drive by the intensity of the corresponding affects; an ‘aim’ reﬂ  ected in the 
particular act of concrete gratiﬁ  cation of the drive; and an ‘object’ 
consisting of displacements from the dominant parental objects of desire.
The introduction of the idea of an aggressive or ‘death’ drive, 
arrived at later in Freud’s
(7, 8) writing, stemmed from his observa-
tions of the profound self-destructive urges particularly manifest in the psychopathology of major depression and suicide, and of the ‘repetition compulsion’ of impulse-driven behaviour that frequently seemed to run counter to the pleasure principle that supposedly governed unconscious drives. He never spelled out the details of the aggressive drive as to its origins. This issue was taken up later by Klein,

(9) Fairbairn,(10) Winnicott,(11) Jacobson,(12) and Mahler and 
her colleagues.(13) Freud described drives as intermediate between 
the body and the mind; the only thing we knew about them, Freud suggested,
(14) were ‘representations and affects’ .
The structure and functions of the ego
While the id is the seat of the unconscious drives, and functions according to the ‘primary process’ of the dynamic unconscious, the ego, Freud
(5) proposed, is the seat of consciousness as well as 
of unconscious defence mechanisms that, in the psychoanalytic treatment, appear as ‘resistances’ to free association. The ego

of unconscious defence mechanisms that, in the psychoanalytic treatment, appear as ‘resistances’ to free association. The ego 
functions according to the logical and reality-based principles of ‘secondary process’ , negotiating the relations between internal and external reality. Guided by the reality principle, it exerts control over perception and motility; it draws on preconscious material, controls ‘attention cathexes’ and permits motor delay as well as selection of imagery and perception. The ego is also the seat of basic affects, particularly anxiety as an alarm signal against the danger of emergence of unconscious, repressed impulses. This alarm signal may turn into a disorganized state of panic when the ego is ﬂ  ooded with external perceptions that activate unconscious 
desire and conﬂ  icts, or with overwhelming, traumatic experiences 
in reality that resonate with such repressed unconscious conﬂ  icts,

in reality that resonate with such repressed unconscious conﬂ  icts, 
and overwhelm the particularly sensitized ego in the process. The fact that the ego was seen by Freud as the seat of affects, and that affects had previously been described by him as discharge phenom-
ena reﬂ  ecting drives (together with their mental representations) 
tended to dissociate affects from drives in psychoanalytic theory, in contrast to their originally being equated in Freud’s early formula-tions. As we shall see, this issue, the centrality of affects in psychic reality and interactions, has gradually re-emerged as a major aspect of contemporary psychoanalytic thinking.
Freud originally equated the ‘I’ , i.e. the categorical self of the

Freud originally equated the ‘I’ , i.e. the categorical self of the 
philosophers, with consciousness; later, once he established the theory of the ego as an organization of both conscious and uncon-scious functions, he at times treated the ego as if it were the subjec-tive self, and at other times, as an impersonal organization of func-tions. Out of this ambiguity evolved the contemporary concept of the self within modern ego psychology as well as in British and American object relations and cultural psychoanalytic contribu-tions.
(15) An alternative theory of the self was proposed by Kohut(16)
the originator of the self-psychology approach within contemporary psychoanalysis.
Nowadays, an integrated concept of the self as the seat of subjec-

tivity is considered an essential structure of the ego, and the concept of ‘ego identity’ refers to the integration of the concept of the self: because of developmental processes in early infancy and childhood better understood today, an integrated self-concept usually goes hand-in-hand with the capacity for an integrated concept of signiﬁ  -
cant others. An unconscious tendency towards primitive dissociation or ‘splitting’ of the self-concept and of the concepts of signiﬁ  cant 
objects runs counter to such integration: we shall return to this pro-cess later. Already Freud,
(17) in one of his last contributions, described 
a process of splitting in the ego as a way of dealing with intolerable intrapsychic conﬂ  ict, thus opening up the road for considering

a process of splitting in the ego as a way of dealing with intolerable intrapsychic conﬂ  ict, thus opening up the road for considering 
splitting processes of the ego as an alternative, pathological defence against intolerable intrapsychic conﬂ  ict (alternative, that is, to the 
repression of that conﬂ  ict and to drawing important related ego 
functions into repression as well).
Character, from a psychoanalytic perspective, may be deﬁ  ned as 
constituting the behavioural aspects of ego identity (the self-concept) and the internal relations with signiﬁ  cant others (the 
internalized world of ‘object relations’). The sense of personal iden-tity and of an internal world of object relations, in turn, reﬂ  ect the 
subjective side of character. It was particularly the ego psychologi-cal approach—one of the dominant contemporary psychoanalytic 
schools—that developed the analysis of defensive operations of the

schools—that developed the analysis of defensive operations of the 
ego, and of pathological character formation as a stable defensive organization that needed to be explored and resolved in the 3.1 psychoanalysis: freud’s theories and their contemporary development

SECTION 3  psychodynamic contributions to psychiatry 296
psychoanalytic treatment. In the process, ego psychology contrib-
uted importantly to the psychoanalytic treatment of personality disorders.
Personality disorders reﬂ  ect typical constellations of pathological 
character traits derived from abnormal developmental processes under the inﬂ  uence of unconscious intrapsychic conﬂ  icts. The 
description of ‘reaction formation’ as one of the defences of the ego led Freud to the description of the ‘oral’ , ‘anal’ , and ‘genital’ charac-ters, particularly to the description of the obsessive–compulsive personality as a typical manifestation of reaction formations against anal drive derivatives. This was followed by the description by Abraham
(18) of the hysterical personality as a consequence

(18) of the hysterical personality as a consequence 
of multiple reaction formations against the female castration complex. Over the years, psychoanalytic explorations led to the description of a broad spectrum of pathological character con-stellations, which today are a part of the spectrum of personality disorders.
Perhaps the most important psychoanalytic contribution to char-
acter pathology and the personality disorders is the clinical descrip-tion of the narcissistic personality disorder. While Freud provided the basic elements that led to its eventual description, psychoanalytic understanding and treatment, it was not he who crystallized the concepts of normal and pathological narcissism. Freud
(19) conceptu-
alized narcissism as the libidinal investment of the ego or self, in contrast to the libidinal investment of signiﬁ  cant others (‘objects’).

alized narcissism as the libidinal investment of the ego or self, in contrast to the libidinal investment of signiﬁ  cant others (‘objects’). 
In proposing the possibility of a withdrawal of libidinal investment from others with an excessive investment in the self as the basic feature of narcissistic pathology, he pointed to a broad spectrum of psychopathology, and thus ﬁ  rst stimulated the contribution 
of Abraham,
(20) and later those of Klein,(21) Rosenfeld,(22)
Grunberger,(23) Kohut,(16) Jacobson,(12) and Kernberg.(24) Thus, 
crystallized the description of the narcissistic personality as a disor-der derived from a pathological integration of a grandiose self as a defence against unbearable aggressive conﬂ  icts, particularly around 
primitive envy.
The superego in normality and pathology
In his analysis of unconscious intrapsychic conﬂ  icts between drive

In his analysis of unconscious intrapsychic conﬂ  icts between drive 
and defence, Freud regularly encountered unconscious feelings of guilt in his patients, reﬂ  ecting an extremely strict, unconscious 
infantile morality, which he called the superego. This unconscious morality could lead to severe self-blame and self-attacks, and par-ticularly, to abnormal depressive reactions, which he came to regard as expressing the superego’s attacks on the ego. It was particularly in studying normal and pathological mourning, where Freud
(6)
arrived at the idea of excessive mourning and depression as reﬂ  ect-

(6)
ing the unconscious internalization of the representation of an ambivalently loved and hated lost object. In unconsciously identi-fying the self with that object introjected into the ego, the individual now attacked his or her own self in replacement of the previous unconscious hatred of the object; and the internalization of aspects of that object into the superego reinforced the strictness of the individual’s pre-existing unconscious infantile morality.
Freud traced the origins of the superego to the overcoming of the 
Oedipus complex via unconscious identiﬁ  cation with the parent of 
the same gender: in internalizing the Oedipal parent’s prohibition against the rivalry with him or her and the unconscious death wishes regularly connected with such a rivalry, and against the incestuous desire for the parent of the other gender, this internal-

ization crystallized an unconscious infantile morality. The super-ego, thus based upon prohibitions against incest and parricide, and a demand for submission to, and identiﬁ  cation with the Oedipal 
rival, became the guarantor of the capacity for identiﬁ  cation with 
moral and ethical values in general. In simple terms, the little boy renounces mother out of fear and love of father, takes father’s fantasized prohibition against the little boy’s sexuality into the superego as a fundamental prohibition, and establishes an identiﬁ  -
cation with his father in the consolidation of his character struc-ture. The little boy thus enacts the unconscious fantasy that, in identifying w ith father, he will gradually grow into his role, and 
satisfy his sexual desire in the distant future, by choosing another 
woman who, unconsciously and symbolically, will represent mother. The superego thus introduces a new time perspective into the functioning of the psychic apparatus.

Freud also described the internalization of the idealized represen-
tations of both parents into the superego in the form of the ‘ego ideal’ . He suggested that the earliest sources of self-esteem, derived from mother’s love, gradually ﬁ  xated by the baby’s and small child’s inter-

nalizations of the representations of the loving mother into the ego ideal, led to the parental demands becoming internalized as well. In other words, normally self-esteem is maintained both by living up to the expectations of the internalized idealized parental objects, and by submitting to their internalized prohibitions. This consider-ation of self-esteem regulation leads to the clinical concept of narcis-sism as normal or pathological self-esteem regulation, in contrast to the theoretical concept of narcissism as the libidinal investment of the self.
The superego, in summary, is a mental structure constituted by 
the internalized demands and prohibitions from the parental objects 
of childhood, the ‘heir to the Oedipal complex’ . This unconscious structure is of fundamental importance in determining unconscious 
‘ﬁ xations’ to infantile prohibitions against drive derivatives and

‘ﬁ xations’ to infantile prohibitions against drive derivatives and 
the corresponding unconscious motivation for the activation of a broad spectrum of ego defences against them, thus preventing the ego from responsibility-examining and reintegrating unresolved pathogenic conﬂ  icts from early childhood. In health, this internal 
sense of unconscious morality is the underpinning of moral and ethical systems. Excessive superego severity, usually derived from excessive parental strictness, determines excessive repressive mecha-nisms and ego inhibitions, irrational moralistic behaviour, or patho-logical activation of depression and loss of self-esteem.
Having thus summarized the basic psychoanalytic theory of 
motivation (drives), of development (the stages of development from the early oral phase to the dominance of the Oedipal complex), of structure (the tripartite model), and their implications for psychopathology, I shall now describe more speciﬁ  cally the contem-

porary psychoanalytic theory of psychopathology and of psychoana-lytic treatment.
Psychoanalytic treatment
The psychoanalytic theory of psychopathology
The psychoanalytic theory of psychopathology proposes that the clinical manifestations of the symptomatic neuroses, character pathology, perversions, sexual inhibitions, and selected types of psy-chosomatic and psychotic illness reﬂ  ect unconscious intrapsychic 
conﬂ icts between drive derivatives following the pleasure principle,

297
defensive operations reﬂ  ecting the reality principle, and the uncon-
scious motivations of the superego. Unconscious conﬂ  icts between 
impulse and defence are expressed in the form of structured con-ﬂ icts between the agencies of the tripartite structure: there are ego 
defences against impulses of the id; the superego motivates inhibi-tions and restrictions in the ego; at times the repetitive, dissociated expression of id impulses (‘repetition compulsion’) constitutes an effective id defence against superego pressures. The resolution of unconscious conﬂ  icts implies the analysis of all these intersystemic 
conﬂ icts.
All these conflicts are expressed clinically by three types of 
phenomena:
1 inhibitions of normal ego functions regarding sexuality, 
intimacy, social relations, work, and affect activation;
2 compromise formations between repressed impulses and the 
defences directed against them;
3 dissociative expression of impulse and defence.

The last category implies a dominance of the splitting mechanisms 
referred to before; these have acquired central importance in the understanding of severe character pathology as reﬂ  ected in contem-
porary psychoanalytic thinking.
The structural formulation of the 
psychoanalytic method
Psychoanalytic treatment consists, in essence, in facilitating the 
reactivation of the pathogenic unconscious conﬂ  icts in the treat-
ment situation by means of a systematic analysis of the defensive operations directed against them. This leads to the gradual emer-gence of repressed impulses, with the possibility of elaborating them in relation to the analyst, and their eventual adaptive integra-tion into the adult ego. Freud
(25) had described the concept of

(25) had described the concept of 
‘sublimation’ as an adaptive transformation of unconscious drives: drive derivatives, converted into a consciously tolerable form, are permitted gratiﬁ  cation in a symbolic way while their origin remains 
unconscious. The result of this process is an adaptive, non-defensive compromise formation between impulse and defence. In analysis, the gradual integration into the patient’s conscious ego of uncon-scious wishes and desires from the past and the understanding of the phantasized threats and dangers connected with them, facili-tates their gradual elaboration and sublimatory expression in the consulting room and in everyday life as well.
The object-relations theory formulation of 
psychoanalytic treatment
In the light of contemporary object-relations theory, the formula-
tion based upon the structural theory (resolution of unconscious conﬂ  icts between impulse and defence) has changed, in the sense

tion based upon the structural theory (resolution of unconscious conﬂ  icts between impulse and defence) has changed, in the sense 
that all unconscious conﬂ  icts are considered to be imbedded in 
unconscious internalized object relations. Such internalized object relations determine both the nature of the defensive operations and of the impulses against which they are directed. These inter-nalized object relations constitute, at the same time, the ‘building blocks’ of the tripartite structure of id, ego, and superego. Object-relations theory proposes that the gradual analysis of intersystemic conﬂ  icts between impulse and defence (structured into conﬂ  icts 
between ego, superego, and id) decomposes the tripartite structure into the constituent conflicting internalized object relations. These object relations are reactivated in the treatment situation in

the form of an unconscious relation between self and signiﬁ  cant 
others replicated in the relation between patient and analyst, i.e. the ‘transference’ .
The transference is the unconscious repetition in the ‘here and 
now’ of unconscious, conﬂ  icting pathogenic relationships from the 
past. The transference reﬂ  ects the reactivation of the past conﬂ  ict not 
in the form of a memory, but in the form of a repetition. This repeti-tion provides essential information about the past, but constitutes, at the same time, a defence in the sense that the patient repeats instead of remembering. Therefore, transference has important informative features that need to be facilitated in their development, and defen-sive features that need to be therapeutically resolved once their nature has been clariﬁ  ed. Transference analysis is the fundamental ingredient 
of the psychoanalytic treatment.
The psychoanalytic treatment process

The psychoanalytic treatment consists of the creation of an atmosphere of safety in which a patient is willing to try to express whatever comes to mind. In 45 to 50 min sessions, three to ﬁ  ve 
times per week, the patient usually reclines on a couch while the analyst, generally sitting behind the patient, helps the patient become aware of his or her defensive operations (‘resistances’) by means of interpretations. The systematic interpretation of resistances gradually permits an ever-growing freedom of free association, and helps the patient to become aware of his or her unconscious desires and fears, phantasies and terrors, traumatic situations, and unre-solved mourning. Defensive operations are usually classiﬁ  ed as ego

defences (in the form of the mechanisms listed earlier), superego defences in the form of excessive guilt feelings activated during the treatment, id resistances in the form of repetition compulsion, 
the development of secondary gain from symptoms as a powerful resistance, and, last and most importantly, the transference as the 
dominant resistance and source of information.
Gill,
(26) in a classical definition that is still relevant today, 
proposed the deﬁ  nition of psychoanalysis as a treatment that facili-
tates the development of a ‘regressive transference neurosis’ and its resolution by means of interpretation alone, carried out by the analyst from a position of technical neutrality. Let us deﬁ  ne these 
concepts.
‘Regression’ refers to the patient’s return to earlier experiences

concepts.
‘Regression’ refers to the patient’s return to earlier experiences 
(temporal regression), and modes of functioning (structural and formal regression) under the effect of the analysis of resistances, and is an expression of the reactivation of his unconscious conﬂ  icts from 
the past in the transference. In essence, the patient activates or enacts earlier object relations in the transference. Certain past stages of development where particular traumatic experiences occurred act as gathering points (‘ﬁ  xations’) that foster regression towards them. 
The concept of a regressive transference neurosis refers to the gradual 
gathering into the relationship with the analyst of the patient’s most important past pathogenic experiences and unconscious conﬂ  icts.

gathering into the relationship with the analyst of the patient’s most important past pathogenic experiences and unconscious conﬂ  icts. 
The concept of a regressive transference neurosis has been largely abandoned in practice because, particularly in patients with severe character pathology, transference regression occurs so early and consistently that the gradual development of a regressive transference neurosis is no longer a useful concept.
Gill’s proposal that the resolution of the transference be achieved 
‘by interpretation alone’ , refers to ‘interpretation’ as a set of the psychoanalyst’s interventions that starts with ‘clariﬁ  cation’ of the 3.1 psychoanalysis: freud’s theories and their contemporary development

SECTION 3  psychodynamic contributions to psychiatry 298
patient’s subjective experiences communicated by means of free 
association, expands with the tactful ‘confrontation’ of aspects of the patient’s patterns of behaviour that are expressed in a dissociated or split-off manner from his subjective awareness, and thus comple-ments the total expression of his intrapsychic life in the treatment situation, and ﬁ  nally evolves into ‘interpretation per se’ . Interpretation 
per se implies the formulation of hypotheses regarding the uncon-

scious meanings in the ‘here and now’ of the patient’s material, and the relation of these unconscious meanings with the ‘there and then’ of the patient’s unconscious, past pathogenic experiences. The analy-sis of the transference is ‘systematic’ , in the sense that all emerging transference dispositions are interpreted, ideally, in the natural sequence of their emergence in the analytic situation. Gill’s phrase, ‘by interpretation alone’ , implies that the psychoanalyst abstains from measures other than helping the patient to fully understand the unconscious conﬂ  icts activated in the here and now. Thus, providing 
guidance about life decisions, or attempting to modify the patient’s behaviour or state by means of praise, prohibition, or reward is not part of the psychoanalytic method of treatment.
The concept of ‘technical neutrality’ refers to the analyst’s impar-

tiality regarding both impulse and defence, with a concerned objec-tivity that provides a helpful collaboration with the patient’s efforts to come to grips with his intrapsychic conﬂ  icts.
This deﬁ  nition of the nature of psychoanalytic treatment needs to 
be complemented with the contemporary concepts of ‘transference’ , ‘countertransference’ , ‘acting out’ , and ‘working through’ .
An object-relations theory model of the 
transference and countertransference
Modern object-relations theory, further explored below, and pre-
sented in more detail in terms of particular schools in Chapter 3.2, proposes that, in the case of any particular conﬂ  ict around sexual 
or aggressive impulses, the conﬂ  ict is imbedded in an internalized

or aggressive impulses, the conﬂ  ict is imbedded in an internalized 
object relation, i.e. in a repressed or dissociated representation of the self (‘self-representation’) linked with a particular representa-tion of another who is a signiﬁ  cant object of desire or hatred 
(‘object representation’). Such units of self-representation, object representation, and the dominant sexual, dependent or aggressive affect linking them are the basic ‘dyadic units’ , whose consolidation will give rise to the tripartite structure. Internalized dyadic rela-tions dominated by sexual and aggressive impulses will constitute the id; internalized dyadic relations of an idealized or prohibitive nature the superego, and those related to developing psychosocial 
functioning and the preconscious and conscious experience,

functioning and the preconscious and conscious experience, 
together with their unconscious, defensive organization against unconscious impulses, the ego. These internalized object relations are activated in the transference  with an alternating role distribu-
tion, i.e. the patient enacts a self-representation while projecting the corresponding object representation onto the analyst at times, while at other times projecting his self-representation onto the analyst and identifying with the corresponding object representa-tion. The impulse or drive derivative is reﬂ  ected by a dominant, 
usually primitive affect disposition linking a particular dyadic 
object relation; the associated defensive operation is also represent-
ed unconsciously by a corresponding dyadic relation between a self-representation and an object representation under the domi-nance of a certain affect state.For example, a conﬂ  ict between unconscious aggression and

unconscious guilt feelings, respectively located in id and superego, is clinically represented by manifestations of a guilt-provoking object representation relating to a guilty self (the superego defence), and an enraged self-representation attempting to attack a threatening or frustrating object representation (the id impulse). The development of the transference, therefore, consists of a sequence of activation of such impulsively determined and defensively determined internal-ized object relations and their systematic clariﬁ  cation, confrontation, 
and interpretation by the analyst.
The concept of countertransference , originally coined by Freud as 
the unresolved, reactivated transference dispositions of the analyst is currently deﬁ  ned as the total affective disposition of the analyst in

the unresolved, reactivated transference dispositions of the analyst is currently deﬁ  ned as the total affective disposition of the analyst in 
response to the patient and his or her transference, shifting from moment to moment, and providing important data of information to the analyst. The countertransference, thus deﬁ  ned, may be par-
tially derived from unresolved problems of the analyst, but stems as well from the impact of the dominant transference reactions of the patient, from reality aspects of the patient’s life, and sometimes from aspects of the analyst’s life situation that are emotionally activated in the context of the transference developments. In general, the stron-ger the transference regression, the more the transference determines 
the countertransference; thus the countertransference becomes 
an important diagnostic tool. The countertransference includes both the analyst’s empathic identiﬁ  cation with a patient’s central

an important diagnostic tool. The countertransference includes both the analyst’s empathic identiﬁ  cation with a patient’s central 
subjective experience (‘concordant identiﬁ  cation’) and the analyst’s 
identification with the reciprocal object or self-representation (‘complementary identiﬁ  cation’) unconsciously activated in the 
patient as part of a certain dyadic unit, and projected onto the analyst.
(27) In other words, the analyst’s countertransference implies 
an identiﬁ  cation with what the patient cannot tolerate in him- or 
herself, and must dissociate, project, or repress.
At this point, it is important to refer to certain primitive defen-
sive operations that were described by Klein(9) and her school in

sive operations that were described by Klein(9) and her school in 
the context of the analysis of severe character pathology. Primitive defensive operations are characteristic of patients with severe per-sonality disorders, and emerge in other cases during periods of regression. They include splitting, projective identiﬁ  cation, denial, 
omnipotence, omnipotent control, primitive idealization, and devaluation (contempt). All these primitive defences centre around splitting, i.e. an active dissociation of contradictory ego (or self) experiences as a defence against unconscious intrapsychic conﬂ  ict. 
They represent a regression to the phase of development (the ﬁ  rst 2 
to 3 years of life) before repression and its related mechanisms mentioned are established.
Primitive defensive operations present important behavioural

Primitive defensive operations present important behavioural 
components that tend to induce behaviours or emotional reactions 
in the analyst, which, if the analyst manages to ‘contain’ them, permit 
him to diagnose in himself projected aspects of the patient’s experi-ence. Particularly ‘projective identiﬁ  cation’ is a process in which:
1 the patient unconsciously projects an intolerable aspect of self-
experience onto (or ‘into’) the analyst;
2 the analyst unconsciously enacts the corresponding experience 
(‘complementary identiﬁ  cation’);
3 the patient tries to control the analyst, who now is under the 
effect of this projected behaviour;
4 the patient meanwhile maintains empathy with what is projected.

299
This scenario is in contrast to the more mature mechanism of 
‘projection’ , secondary to repression, where there is no longer any conscious emotional contact with what is projected. Such comple-mentary identiﬁ  cation in the countertransference permits the analyst 
to identify him- or herself through his own experience with the aspects of the patient’s experience communicated by means of 
projective identiﬁ  cation. This information complements what the 
analyst has discovered about the patient by means of clariﬁ  cation 
and confrontation, and permits the analyst to integrate all this infor-mation in the form of a ‘selected fact’ that constitutes the object of interpretation. Interpretation is thus a complex technique that is very much concerned with the systematic analysis of both transference and countertransference.
Contemporary trends of the 
Contemporary psychoanalytic technique can be seen as having

Contemporary psychoanalytic technique can be seen as having 
evolved from a ‘one person psychology’ into a ‘two person psychol-ogy’ and then into a ‘three person psychology’ . The concept of ‘one person psychology’ refers to Freud’s original analysis of the patient’s unconscious intrapsychic conﬂ  icts by analysing the intrapsychic

defensive operations that oppose free association. The ‘two person psychology’ refers to the central focus on the analysis of transfer-ence and countertransference. In the views of the contemporary intersubjective, interpersonal, and self-psychology psychoanalytic schools, the relationship between transference and countertrans-ference is mutual, in the sense that the transference is at least in part a reaction to reality aspects of the analyst, who therefore must be acutely mindful of his contribution to the activation of the transference. The so-called ‘constructivist’ position regarding transference analysis assumes that it is impossible for the analyst 
to achieve a totally objective position outside the transference/countertransference bind.
In contrast, the contemporary ‘objectivist’ position, represented by 
the ‘three person psychology’ approaches of the Kleinian school, the 
French psychoanalytic mainstream, and signiﬁ  cant segments of con-

temporary ego psychology proposes that the analyst has to divide 
him- or herself between one part inﬂ  uenced by transference and 
countertransference developments, and another part that, by means of self-reﬂ  ection, maintains him- or herself outside this process, as 
an ‘excluded third party’ , who, symbolically, provides an early trian-
gulation to the dyadic regression that dominates transference devel-
opments. This triangulation in the treatment situation becomes par-ticularly important in the treatment of severe personality disorders.
The ‘enactment’ of pathogenic past internalized object relations in 
the form of both transference and countertransference developments needs to be differentiated from acting out , the replacement of self-

awareness by often dramatic, and at times, violent action. It is char-acteristic of patients with severe character pathology, and may occur in both patient and analyst under the inﬂ  uence of regression. Acting 
out may occur both during and outside the sessions. While it reﬂ  ects 
an intense defensive operation and resistance, it also offers the opportunity for a very fundamental exploration of a primitive conﬂ  ict, if dealt with by consistent interpretations in as much 
depth as possible. Acting out may also be considered an extreme, 
behavioural manifestation of ‘enactment’ as the usual experience of transference/countertransference manifestations.The repetition compulsion  as a resistance of the id is most prob-

ably a form of acting out as a defence against emotional containment of an extremely painful or traumatic set of experiences. W orking 
through  refers to the repeated elaboration of an unconscious con-
ﬂ ict in the psychoanalytic situation. It is a major task for the analyst, 
who has to be alert to the subtle variation in meanings and implica-tions of what on the surface may appear to be an endless repetition of the same conﬂ  ict in the transference. The patient elaboration of 
the conﬂ  ict that presents itself with these repetitive characteristics 
also implies the function of ‘holding’ originally described by Winnicott.
(11) It consists of the analyst’s capacity to withstand the

(11) It consists of the analyst’s capacity to withstand the 
onslaught of primitive transferences without retaliation, abandon-ment of the patient, or a self-devaluing giving up, and the mainte-nance of a working relationship (or ‘therapeutic alliance’) that addresses itself consistently to the healthy part of the patient, even when the latter is under the control of his most conﬂ  icting behav-
iours. Bion’s concept
(28) of ‘containing’ is complementary to ‘holding’ , 
in the sense that holding deals mostly with the affective disposition of the analyst, and containing with his cognitive capacity to maintain a concerned objectivity and focus on the ‘selected fact’ , permitting the integration in the analyst’s mind what the patient can only express in violently dispersed or split-off behaviour patterns.
Dream analysis  developed in the context of the method of free 
association, and constituted, in Freud’s

(29) view, a ‘royal road to the 
unconscious’ . Freud’s discovery of primary process thinking derived from his method of dream analysis. By now, psychoanalytic thinking has evolved into the view that there are many ‘royal roads’ to the unconscious. The analysis of character defences, for example, or of particular transference complications, may be equally important avenues of entry into the patient’s unconscious mind.
The technique of dream analysis consists, in essence, in asking the 
patient to free associate to elements of the ‘manifest content’ of the dream, in order to arrive at its ‘latent’ content, the unconscious wish defended against and distorted by the unconscious defensive mecha-nisms that constitute the ‘dream work’ , and have transformed the latent content into the manifest dream. The latent content is revealed

with the help of the simultaneous analysis of the way in which the 
dream is being communicated to the analyst, the ‘day residuals’ that may have triggered the dream, the unconscious conﬂ  icts revealed in 
it, and the dominant transference dispositions in the context of 
which the dream evolved. Dreams also provide some residual, uni-versal symbolic meanings that may facilitate the total understanding 
of the latent content.
The analysis of character  may be the single most important ele-
ment of the psychoanalytic method in bringing about fundamental characterological change. Character analysis is facilitated by the patient’s use of reaction formations, i.e. his defensively motivated character traits, as transference resistances. Thus, the activation of defensive behaviours in the transference, reﬂ  ecting the patient’s 
characterological patterns in all interpersonal interactions, facilitates both the analysis of the underlying unconscious conﬂ  icts, and in the

characterological patterns in all interpersonal interactions, facilitates both the analysis of the underlying unconscious conﬂ  icts, and in the 
process, the resolution of pathological character patterns. The result is an increase in the patient’s autonomy, ﬂ  exibility, and capacity for 
adaptation. Character analysis was originally developed by Reich
(30)
within an ego-psychology perspective, but has re-emerged in the work of Rosenfeld
(31) and Steiner(32) in the analysis of ‘pathological 
organizations’ in the transference, within the Kleinian school. Gray
(33) and Busch(34) within an ego-psychological perspective, have 3.1 psychoanalysis: freud’s theories and their contemporary development

SECTION 3  psychodynamic contributions to psychiatry 300
enriched further the technique of character analysis by means of 
detailed exploration of particular characterological defences in the transference.
Character analysis, although not always referred to under this 
speciﬁ  c heading, constitutes a major focus of contemporary psycho-
analytic treatment. In essence, its technique addresses repetitive, ego syntonic behaviour patterns in the transference, raising the patient’s curiosity about their function in the relationship with the analyst, and inviting the patient to associate about this behaviour. Gradually, their exploration makes character resistances ego dystonic, and facil-itates the discovery of the underlying internalized object relations condensed in these pathological character traits, both in their defen-sive and impulsive meanings. The question, to what extent such rigid behaviours should be analysed ﬁ  rst, in order to free the patient’s

capacity for analytic work, or to what extent they should be left for 
later, until more ﬂ  uid conﬂ  icts have been resolved, has been settled in 
favour of the general psychoanalytic technical principle of focusing interpretations upon what is affectively dominant in each hour.
(35)
Affective dominance refers once more to the ‘selected fact’ ,(36) to be 
interpreted. All interpretations are usually carried out from surface to depth, which in practice means ﬁ  rst analysing the object relation 
activated by the need for defence before analysing the corresponding object relation activated by impulse.
The overall objective of psychoanalytic treatment is not only the 
resolution of symptoms and pathological behaviour patterns or characteristics, but fundamental, structural change, that is the expansion and enrichment of ego functions as the consequence of resolution of unconscious conﬂ  ict and the integration of previ-

ously repressed and dynamically active id and superego pressures into ego potentialities. Such change is reﬂ  ected in the increasing 
capacity for both adaptation to and autonomy from psychosocial demands and expectations, and an increased capacity for gratifying and successful functioning in love and work.
Derived modalities of treatment
One of the most important contributions of psychoanalytic theory and technique to the contemporary treatment of a broad spectrum of patients with severe psychopathology who, for various reasons, cannot beneﬁ  t from psychoanalytic treatment proper, is the devel-
opment of psychoanalytic psychotherapy, also called expressive or exploratory psychotherapy, and of supportive psychotherapy (SP) based on psychoanalytic principles. These treatments are explored below.
Psychoanalytic psychotherapy
Psychoanalytic psychotherapy may be characterized by the same basic techniques as psychoanalysis, but with quantitative modiﬁ  ca-

tions that, in combination, result in a qualitative shift in the nature of the treatment. Any given session of psychoanalytic psychotherapy may be indistinguishable from a psychoanalytic session, but over time, the differences emerge quite clearly. Psychoanalytic psycho-therapy utilizes interpretation, but with patients with severe psy-chopathology, a good deal of time must be devoted to clariﬁ  cation 
and confrontation before interpretation can be effective; and inter-pretations of unconscious meanings in the ‘here and now’ occupy the foreground until late in the treatment, when genetic interpreta-tions in the ‘there and then’ become useful.
(15, 37)
In the treatment of patients with severe character pathology,

(15, 37)
In the treatment of patients with severe character pathology, 
transference analysis is the essential focus of psychoanalytic psychotherapy from the very beginning; it must be modiﬁ  ed, how-
ever, by active interpretive connection of transference analysis with exploration in depth of the patient’s daily life situation, an approach made necessary by the predominance of primitive defence opera-tions in these patients. Splitting operations in particular tend to dissociate the therapeutic situation from the patient’s external life, and may lead to severe, dissociated acting out either in the sessions or outside the sessions. Therefore, interpretive linkage between the patient’s external reality and transference developments in the hours becomes central.
In order to enable the therapist to analyse transference develop-
ments in sufﬁ  cient depth, psychoanalytic psychotherapy requires a

ments in sufﬁ  cient depth, psychoanalytic psychotherapy requires a 
minimum frequency of two sessions per week. It is usually carried out in ‘face-to-face’ sessions.
T echnical neutrality is an essential feature of analysis in general, 
but in the treatment of patients with severe character pathology, the need to set limits may necessitate abandoning neutrality again and again, in order to control life- or treatment-threatening acting out. The self-perpetuating nature of acting out in these cases may prove impossible to resolve interpretively without such structuring or setting limits. Whenever the analyst has to abandon technical neu-trality to protect the patient or the treatment, it is essential to explore 
the episode immediately. The transference implications of the thera-

pist’s structuring behaviour must be laid out, followed by the analysis of the transference implications of the patient’s behaviour that neces-sitated the imposition of limits or the initiation of a new structure in the treatment; this in turn is followed by the gradual resolution of the structure or limit setting by interpretive means, thus restoring technical neutrality. In short, technical neutrality in psychoanalytic psychotherapy is an ideal working state that is again and again pre-ventively abandoned and interpretively reinstated.
(15, 37, 38)
Supportive psychotherapy
Supportive psychotherapy based on psychoanalytic theory may also be deﬁ  ned in terms of the three major techniques of interpre-
tation, transference analysis, and technical neutrality. Supportive psychotherapy utilizes the preliminary steps of interpretive tech-nique, i.e. clariﬁ  cation and confrontation, but rarely uses interpre-

tation per se. It seeks to strengthen the ego by bolstering adaptive compromises between impulse and defence through the provision of cognitive support in the form of information, persuasion and advice, and emotional support via suggestion, reassurance, encour-agement, and praise. Supportive psychotherapy may call upon direct environmental intervention by the therapist, relatives, or other mental health personnel engaged in auxiliary therapeutic functions.
(39)
While the transference is seldom interpreted in supportive psycho-
therapy, it is not ignored either. Careful attention to transference developments helps the therapist to analyse any maladaptive trans-ference developments, to call the patient’s attention to the reproduction with the therapist of pathological interactions the patient generally engages in with signiﬁ  cant others, and to encourage the patient to

reduce such pathological behaviours. Pointing out the distorted, unproductive, destructive, or confusing nature of the patient’s behaviour is accompanied by clarifying the patient’s conscious reasons for his behaviour, followed by the transfer or ‘export’ of the knowledge thus achieved to the patient’s relationships outside the treatment. In short, supportive psychotherapy includes the clariﬁ  ca-
tion, reduction, and ‘export’ of the transference, thus contributing to

301
the re-educative functions of supportive psychotherapy together 
with the direct cognitive and affective support of adaptive combina-tions of impulse and defence, and direct supportive environmental interventions.
T echnical neutrality is systematically abandoned in supportive 
psychotherapy, the therapist taking a stance alternatively on the side of the ego, superego, id, or external reality, according to which agency represents, at a certain point, the more adaptive potential for the patient. The main dangers, of course, in supportive psychotherapy are, on the one hand, infantilizing the patient by an excessively sup-portive stance, and, on the other, countertransference acting out as a consequence of the abandonment of the position of technical neu-trality. The therapist carrying out supportive psychotherapy, there-fore, needs a heightened awareness of the risk of these complications. 
Like psychoanalytic psychotherapy, supportive psychotherapy is

Like psychoanalytic psychotherapy, supportive psychotherapy is 
carried out in ‘face-to-face’ sessions. It has the advantage of consider-able ﬂ  exibility regarding its frequency, from several sessions per week, 
to one session a week, or one or two sessions per month, according to the urgency of the patient’s present difﬁ  culties, the long-range objec-
tives of the treatment, and the patient’s ability to tolerate and use the relationship with the therapist.
Indications and contraindications for 
psychoanalysis and derived psychotherapies
The indications  for these three modalities of treatment remain

The indications  for these three modalities of treatment remain 
controversial: with the recognition of the limitations of psycho-analysis in many cases with severe, chronic, life-threatening self-destructive behaviour, such as chronic suicidal behaviour, severe eating disorders, dependence upon drugs or alcohol, and severely antisocial behaviour, psychoanalytic psychotherapy has proven to be a highly effective treatment for many but by no means all patients with these conditions. The differential diagnosis of a spec-trum of severity of antisocial behaviour and those cases of severe self-destructive and antisocial behaviour who are amenable to treatment with psychoanalytic psychotherapy has been one of the important side-products of the psychoanalytic exploration of these cases.
(37)
Supportive psychotherapy, originally conceived of as the treatment

(37)
Supportive psychotherapy, originally conceived of as the treatment 
of choice for patients with severe personality disorders, now may be considered the alternative treatment for those patients with severe personality disorders who are unable to participate in psychoanalytic psychotherapy. The Menninger Foundation Psychotherapy Research Project showed that patients with the least severe psychopathological disturbances tend to respond very positively to all three modalities derived from psychoanalytic theory, although best to standard psychoanalysis.
(40)
Standard psychoanalysis is the treatment of choice for patients 
with neurotic personality organization, that is with good identity integration and a repertoire of defences centring on repression along with sufﬁ  cient severity of illness to warrant such a major therapeutic

intervention. Psychoanalysis has also expanded its scope to some of the severe personality disorders, particularly a broad spectrum of patients with narcissistic personality disorders, patient with mixed hysterical-histrionic features, and selected cases of patients with severe paranoid, schizoid, and sado-masochistic features.
We are still lacking systematic studies of the relationship between 
particular types of psychopathology and outcome with the various psychotherapeutic treatments derived from psychoanalytic theory. As a tentative generalization it may be stated that there is a deﬁ  nite relationship between outcome and the severity of illness in any diag-

nostic category. The least severe cases will respond favourably to either brief psychoanalytic psychotherapy, supportive psychotherapy, or psychoanalysis. Psychoanalysis represents the opportunity for most improvement if the severity of the case warrants psychoana-lytic treatment. For cases of neurotic personality organization of moderate severity, psychoanalysis is the treatment of choice; deﬁ  -
nitely less can be expected in these cases from psychoanalytic psychotherapy. For the most severely ill patients (those with severe identity diffusion, predominance of primitive defences centring on splitting, and general ‘ego weakness’) psychoanalytic psychotherapy is the treatment of choice, with supportive psychotherapy a second choice if psychoanalytic psychotherapy is contraindicated. A few such cases may be able to participate in psychoanalysis and beneﬁ  t 
from it.
In all cases, individualized contraindications  for the respective

from it.
In all cases, individualized contraindications  for the respective 
treatment are important: in the case of psychoanalysis, individual contraindications depend on the questions of ego strength, motiva-tion, introspection or insight, secondary gain of illness, intelligence, and age. In the case of psychoanalytic psychotherapy, secondary gain, the impossibility of control of life- or treatment-threatening acting out, limited intelligence, signiﬁ  cant antisocial features, and a desper-
ate life situation may constitute individual contraindications, partic-ularly when they occur in combination. When psychoanalytic psychotherapy is contraindicated for such reasons, supportive psy-chotherapy becomes the treatment of choice. Participation in sup-portive psychotherapy requires a sufﬁ  cient capacity for commitment

to an ongoing treatment arrangement, and the absence of severe antisocial features as minimal individual requirements. This is not meant to be a complete list, but an illustration of the kind of criteria that become dominant in the individual decisions regarding the selection of the treatment and its contraindications.
Psychoanalytic object-relations theories: 
overview and critique
Given the centrality of object-relations theory in practically all 
contemporary psychoanalytic formulations and treatment approaches, the following summary is included. It should help the reader to further clarify the references made earlier to this theory.
Psychoanalytic object-relations theories may be deﬁ  ned as those

Psychoanalytic object-relations theories may be deﬁ  ned as those 
that place the internalization, structuralization, and reactivation in the transference and countertransference of the earliest dyadic object relations at the centre of their clinical formulations, and of their thinking about motivation, pathogenesis, development, and psychic structure. Internalization of object relations refers to the concept that, in all interactions of the infant and child with the sig-niﬁ cant parental ﬁ  gures, what the infant internalizes is not merely an 
image or representation of the other (‘the object’ of fear, hatred, or desire), but the relationship between the self and the other, in the 
form of a self-image or self-representation linked to an object image 
or object representation by the affect that dominates their interaction. This internal structure replicates in the intrapsychic world both real and phantasied relationships with signiﬁ  cant others.

Several major issues separate different object-relations theories, 
the most important of which is the extent to which the theory is perceived as harmonious with or in opposition to Freud’s traditional drive theory: i.e. whether object relations are seen as replacing drives as the motivational system for human behaviour. From this perspec-tive, Klein,
(9, 21)  Mahler et al.,(13) and Jacobson(12) occupy one pole. 3.1 psychoanalysis: freud’s theories and their contemporary development

SECTION 3  psychodynamic contributions to psychiatry 302
They combine Freud’s dual-drive theory with an object-relations 
theory. For Fairbairn,(10) and Sullivan,(41) on the other hand, object 
relations themselves replace Freud’s drives as the major motivational system. Here, the establishment of gratifying object relations in itself constitutes the major motivational system. Contemporary interper-sonal psychoanalysis as represented by Greenberg and Mitchell,
(42)
based upon an integration of principally Fairbairnian and Sullivanian concepts, asserts the essential incompatibility between drive- and object relations-based models of psychic motivational systems. Winnicott,
(11) Loewald,(43) Sandler,(44) and Sandler and Sandler,(45)
(each for different reasons) maintain an intermediate posture; they perceive the affective frame of the infant–mother relationship as a crucial determinant in shaping the development of drives. While adhering to Freud’s dual-drive theory, Kernberg

(15) considers drives 
supraordinate motivational systems, while affects are their constituent components.
A related controversy has to do with the origin and role of aggres-
sion as motivator of behaviour. Those theoreticians who reject the idea of inborn drives,
(41) or equate libido with the search for object 
relations,(10) conceptualize aggression as secondary to the frustration 
of libidinal needs, particularly traumatic experiences in the early mother–infant dyad. Theoreticians who adhere to Freud’s dual-drive theory, in contrast, believe aggression is inborn and plays an impor-tant part in shaping early interactions: this group includes Klein in particular, and to some extent Winnicott, and ego-psychology object-relations theoreticians such as Kernberg.
(37) Finally, contrast may be 
made between object-relations theories and French approaches, both Lacanian and (non-Lacanian) mainstream psychoanalysis. The French psychoanalytic mainstream,
(46, 47) has maintained close links

(46, 47) has maintained close links 
with traditional psychoanalysis, including the British object-relations theories. Insofar as Lacan
(48) conceptualizes the unconscious as a

(48) conceptualizes the unconscious as a 
natural language and focuses on the cognitive aspects of unconscious development, he underemphasizes affect—a dominant element of object-relations theories. At the same time, however, in postulating a very early Oedipal structuralization of all infant–mother interactions, Lacan emphasizes archaic Oedipal developments, which implicitly links his formulations with those of Kleinian object-relations theory in general. French mainstream analysis also focuses on archaic aspects of Oedipal developments, but places a traditional emphasis on Freud’s dual-drive theory and on the affective nature of the early ego-id. As neither French mainstream nor Lacanian psychoanalysis spells out speciﬁ  c structural consequences of dyadic internalized 
object relations, however, neither would ﬁ  t the deﬁ  nition that frames

object relations, however, neither would ﬁ  t the deﬁ  nition that frames 
the ﬁ eld of object-relations theory as proposed in this chapter.
All object-relations theories focus heavily on the enactment of 
internalized object relations in the transference, and on the analysis of countertransference in the development of interpretive strategies. They are particularly concerned with severe psychopathologies, including those psychotic patients who are approachable with psychoanalytic techniques, borderline conditions, severe narcissistic character pathology, and the perversions (‘paraphilias’). Object-relations theories explore primitive defensive operations and object relations both in cases of severe psychopathology and at points of severe regression with all patients, regarding such exploration as essential in facilitating transference analysis and conﬂ  ict resolution.
The contemporary re-evaluation of Freud’s dual-drive theory

The contemporary re-evaluation of Freud’s dual-drive theory 
that has occurred mostly in France is relevant to the relationship between object-relations theory and drive theory. Perhaps particu-larly the work of Laplanche
(49) and Green(46) has emphasized the central importance of unconscious destructive and self-destructive 
drive manifestations in the form of attacks on object relations, and the central role of unconscious erotization in the mother–infant relationship in libidinal development, all of which tends to link drive theory and object-relations theory in intimate ways.
Another important development within psychoanalytic theory 
has been the growing emphasis on affects as primary motivators, and the centrality of the communicative functions of affects in early development, particularly the infant–mother relationship.
(50) This

(50) This 
emphasis has linked affect theory and object-relations theory quite closely, despite the persistent controversy between those who see affect, particularly peak affect states, as essential representatives of the drives,
(50) and those who stress the psychophysiological nature of 
the affective response, and attempt to replace drive theory with an affect theory.
(51)
The basic (self-representation–object representation) units of

(51)
The basic (self-representation–object representation) units of 
internalized object relations include the representative affects, or else, the constituent affective components of the drives. One might say that the affect of sexual excitement is the central affect of libido, in the same way as the affect of primitive hatred constitutes the central affect of the aggressive or death drive. The id is conceptualized in this object-relations theory model as the sum total of repressed, desired, and feared primitive object relations. The gradual integration of successive layers of persecutory and idealized, prohibitive and demanding, internalized object relations become part of the primi-tive superego, while internalized object relations activated in the service of defence consolidate as part of an integrated self-structure surrounded by integrated representations of significant others. In short, the id or dynamic unconscious, the superego, and the ego

are constituted by different constellations of internalized object 
relations, so that the development of the drives and the development of the psychic apparatus—the tripartite structure—occur hand in hand.
Perhaps the most important practical implication of object-
relations theory is the conception of identiﬁ  cation as a series of 
internalization processes of dyadic units of self-representation and object representation linked by a dominant affect state, ranging from earliest introjections to identiﬁ  cations per se, to the develop-
ment of complex identity formation. Each step includes the inter-nalizing of both self and object representations and their affective interactions under the conditions that prevail at different develop-mental levels.
In the transference of healthier patients, with a well-consolidated

ego identity, the diverse self-representations are relatively stable in their coherent mutual linkage. This fosters the relatively consistent projection onto the analyst of the object representation aspect of the enacted object relationship. In contrast, patients with severe identity diffusion lack such linkage of self-representations into an integrated self. They tend to alternate rapidly between projection of self and object representations in the transference, so that the analytic situation seems chaotic. Systematic interpretation of how the same internal-ized object relation is enacted again and again with rapid role rever-sals between patient and analyst makes it possible to clarify the nature of the unconscious object relation, and the double splitting of self-representation from object representation and idealized from persecutory object relations. This process of interpretation promotes integration of the split representations, which characterize severe psychopathology and

object representation and idealized from persecutory object relations. This process of interpretation promotes integration of the split representations, which characterize severe psychopathology and account for the marked instability of the emo-tions, behaviour, and interpersonal relationships of these patients.

303
Kernberg(37) proposes that affects are the primary motivational 
system and that, internalized or ﬁ  xated as the very frame of inter-
nalized ‘good’ and ‘bad’ object relations, affects are gradually inte-grated into libidinal and aggressive drives to form hierarchically supraordinate motivational systems. In other words, primitive affects are the ‘building blocks’ of the drives. He sees unconscious intrapsychic conﬂ  icts as always between the following:
1 certain units of self and object representations under the impact 
of a particular drive derivative (clinically, a certain affect disposi-tion reﬂ  ecting the drive derivative side of the conﬂ  ict);
2 contradictory or opposing units of self and object representa-
tions and their respective affect dispositions reﬂ  ecting the defen-
sive structure.
Unconscious intrapsychic conﬂ  icts are never simply between 
impulse and defence; rather, both impulse and defence ﬁ  nd expres-

sion, respectively, through certain internalized object relations.
In patients with borderline personality organization and severe 
conﬂ  icts around early aggression, splitting mechanisms stabilize 
such dynamic structures within an ego-id matrix and permit the contradictory aspects of these conﬂ  icts to remain at least partially 
conscious, in the form of primitive, mutually split-off, idealized, and persecutory transferences. In contrast, patients with neurotic personality organization present impulse–defence conﬁ  gurations 
that contain speciﬁ  c unconscious wishes of an integrated though 
infantile self, reﬂ  ecting sexual and aggressive drive derivatives embed-

ded in unconscious phantasies relating to the Oedipal objects. Repressed unconscious wishes, however, always come in the form of corresponding units composed of self-representation and object representation and affect linking them.
Patients with neurotic personality organization present well-
integrated superego, ego, and id structures; within the psychoana-
lytic situation, the analysis of resistances brings about the activation, in the transference, ﬁ  rst of relatively global characteristics of these 
structures, and later, the internalized object relations of which they are composed. Oedipal conﬂ  icts dominate the dynamic unconscious 
of these patients. The analysis of drive derivatives occurs in the context of the analysis of the relation of the patient’s infantile self to signiﬁ  -
cant parental objects as projected onto the analyst.

Patients with severe personality disorders or borderline personality 
organization, in contrast, show a predominance of psychic represen-tations of pre-Oedipal conﬂ  icts, with pre-Oedipal aggression, in 
particular, condensed with representations of the Oedipal phase. Conﬂ  icts are not predominantly repressed and therefore uncon-
sciously dynamic: rather, they are avoided by being represented in mutually dissociated ego states reﬂ  ecting the defence of primitive 
dissociation or splitting. The activation of primitive object relations that predate the consolidation of ego, superego, and id is manifest in the transference as apparently chaotic affect states, which have to be analysed in sequential steps as follows:
1 the clariﬁ  cation of a dominant primitive object relation in the 
transference, with its corresponding self and object representa-tion, and the dominant affect linking them;

2 the analysis of the alternative projection of self and object repre-
sentation onto the therapist, while the patient identiﬁ  es with a 
reciprocal self or object representation of this object relation-ship, leading to the patient’s gradual capacity to become aware of his identiﬁ  cation with an object in that relationship;3 the interpretive integration of mutually split-off, idealized and per-
secutory ‘part object’ relations with the characteristics mentioned.
This analysis may gradually bring about a transformation of 
mutually split, (‘part object’) relations into ‘total object’ relations, or of primitive transferences (largely reﬂ  ecting Mahler’s stages

mutually split, (‘part object’) relations into ‘total object’ relations, or of primitive transferences (largely reﬂ  ecting Mahler’s stages 
of development that predate object constancy) into the advanced transferences of the Oedipal phase. In other words, a gradual integra-tion of self-representations into an integrated self-concept, and a parallel integration of signiﬁ  cant object representations into inte-
grated concepts of signiﬁ  cant others develop ﬁ  rst in the transference, 
and later generalize in the patient’s relations with significant others. The analyst’s exploration of his or her countertransference, including concordant and complementary identiﬁ  cations in the 
countertransference,
(27) facilitates transference analysis; and the 
analysis of primitive defensive operations, particularly splitting and projective identiﬁ  cation in the transference, also contributes to 
strengthening the patient’s ego.
Treatment results: research on outcome

The psychoanalytic profession has been slow in developing system-atic research on treatment process and results, let alone controlled randomized comparison of treatment methods evaluating efﬁ  cacy 
and efﬁ  ciency. The reasons are multiple: the complexity of the 
psychoanalytic treatment, and the changes in its technique; the long duration of treatment, making systematic research, and controlled comparison with other treatment methods difﬁ  cult; the 
private nature of psychoanalytic exploration in the context of patients’ regression, and the related concerns over disturbing the therapeutic relationship by recording or direct observation. In addition, the general methodology of psychotherapy research evolved to a degree of sophistication applicable to the evaluation of psychoanalytic treatment only in recent decades. With all these reservations, signiﬁ  cant progress has been made, and outcome

studies are beginning to be available.
The Menninger Psychotherapy Research Project, a naturalistic 
study comparing psychoanalysis, psychoanalytic psychotherapy, and SP , showed psychoanalysis to be the most effective of these approaches with patients presenting relatively good ego strength, while patients with severe ego weakness—what nowadays would be described as presenting severe personality disorders or borderline personality organization—improved most with psychoanalytic psychotherapy.
(39) This research also showed how important 
supportive elements were throughout all modalities of treatment.(52)
A comprehensive review of outcome studies on psychoanalytic psychotherapy and psychoanalysis by Bachrach et al.
(53) concluded 
that the improvement rates are in the 60 to 90 per cent, but it also pointed to limitations and problems in the methodology utilized.
Recently, studies regarding the treatment process and outcome of

Recently, studies regarding the treatment process and outcome of 
psychoanalysis and psychoanalytic psychotherapy have become more precise in deﬁ  ning the speciﬁ  c treatment variables of psychothera-
peutic and psychoanalytic treatments, and several systematic studies on psychoanalytic psychotherapies and psychoanalysis are in prog-ress.
(54) A recent study by the Stockholm Outcome of Psychoanalysis 
and Psychotherapy Project has found, on the basis of a relatively large patient population, that psychoanalytic treatment, in comparison with psychoanalytic psychotherapy, obtained a signiﬁ  cantly higher 
degree long-range symptomatic improvement.
(55) The extent 
to which the psychotherapist had years of experience linked with 3.1 psychoanalysis: freud’s theories and their contemporary development

SECTION 3  psychodynamic contributions to psychiatry 304
appropriate, long-term supervisory experiences, i.e. an ‘experiential 
learning cluster’ , was related to treatment outcome, in the sense that those therapists with long experiences in doing teaching or supervi-sion of psychotherapy had a signiﬁ  cantly better outcome than thera-
pists who only had been in superv ision or personal therapy for long 
periods. It also appeared that the maintenance of a rigid ‘psychoana-lytic’ attitude as part of a psychoanalytic psychotherapy was not as effective as a more ﬂ  exible shift in techniques in psychotherapy, but 
not in analysis proper.
(56) A manualized psychoanalytic psychother-
apy for a speciﬁ  c patient population, namely, the psychotherapy 
research project of the Cornell Personality Disorders Institute’s man-ualized treatment for borderline patients has provided evidence for the efﬁ  cacy of the treatment with severely ill patients. This treatment,

called Transference Focused Psychotherapy (TFP) was found to be more effective than treatments as usual (TAU) for borderline patients,
(38) and, compared to dialectic behaviour therapy (DBT), 
and supportive psychotherapy (SP) in a randomized controlled study, proved as effective as DBT and SP in improving depression, anxiety, global functioning, and social adjustment at the end of 1 year of treatment. It also was more effective in reducing aggression than DBT and SP , and the only one to improve reﬂ  ective function 
(RF), an index of mentalization, that is the patient’s capacity for self-reﬂ ection and appropriate assessment of others in depth.
(57,58)
(Bateman and Fonagy(59, 60) have found that mentalization-based 
therapy (MBT), another form of psychoanalytic psychotherapy was more effective than treatment as usual (TAU) in the treatment of borderline patients in a day hospital setting. Further developments of MBT research will be referred to in Sections 3, 5, and 6.

In summary, process research has predated outcome research 
on psychoanalysis and derived psychotherapies; major efforts at outcome research are being made, and should contribute to clarify the effects, not only of psychoanalysis proper, but also of the derived psychotherapeutic approaches now being carried out in clinical practice.
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BPD. Journal of Personality Disorders ,18, 36–51.3.1 psychoanalysis: freud’s theories and their contemporary development

3.2
Object relations, attachment 
theory, self-psychology, and interpersonal psychoanalysis
Despite many splits and schisms, dating back to Adler and Jung’s 
early break with Freud, there has been an enduring attempt within psychoanalysis to hold to a central psychodynamic vision and to ﬁ nd common ground between differing theoretical and clinical 
approaches. The aim of this chapter is to describe the work of some of the major ﬁ  gures who have extended and developed Freud’s 
ideas, pointing to areas of both conﬂ  ict and convergence, and, 
wherever possible, to relate their concepts to the everyday practice of psychiatry.
From drive theory to object relations

Psychoanalysis started its life as a ‘drive theory’ or ‘dual instinct’ theory—the idea that mental life and its pathologies could be understood in terms of the interplay between the erotic and death drives, and the ways in which these were repressed, or expressed either covertly via ‘conversion’ , or directly. As Freud’s thought evolved, so new paradigms began to emerge. Drive theory had little to say about relationships: other people appear merely as satisﬁ  ers 
or thwarters of an individual’s instinctual needs. Freud began to ask how children, and later adults, reconciled their own wishes and desires—their drives or instincts—with those of their care-givers and peers. Struggling with this problem, while remaining within the conﬁ  nes of drive theory, he now differentiated between

self-love, or narcissism, and other, or ‘anaclitic’ , love, directed out-wards. In this model, the individual gradually emerges from 
egg-like self-absorption and healthy narcissism into the world of 
relationships.
A further push towards a more relational theory came from 
Abraham, later to become Melanie Klein’s analyst, who noticed the parallels between the phenomena of grief and depression. The intense psychic pain and disruption associated with a loss suggested a much more intimate connection between relationships and the architecture of the psyche than drive theory would allow. ‘The unconscious’ is not so much a repository of drives and desires, but an inner world populated by signiﬁ  cant others or ‘objects’ . The self 
is forged out of these ‘objects’ with whom the individual has or has had important relationships: ‘the shadow of the object falls on the ego’ .

(1) A further theoretical move arose from considering the origins of conscience and ideals. It is a matter of observation that 
much of development depends on processes of imitation and identiﬁ  cation. The developing child internalizes, or ‘introjects’ , his 
or her parent’s values and standards. How, and where in the psyche, does this process take place? In Freud’s ‘tripartite model’ , the ‘superego’ , alongside the ego (i.e. executive and experienced self) and the id (the locus of desire and dreaming), is the focus for these internalized parental values and aspirations. The inner world now contained not just ‘objects’ , but value-based relations between 
them: prohibitions, encouragements, injunctions, and gratiﬁ  ca-
tions. Much of post-Freudian theory consists of attempts to develop and elaborate these ideas.

Object relations 1: Klein, Fairbairn, and 
their successors
This was the state of theoretical play in psychoanalysis when 
Melanie Klein  ﬁ rst burst on to the scene in the late 1920s. Like 
Freud, her work can be divided into a number of phases.(2, 3)
Psychoanalysis is concerned with early mental life, which it sees 
as the basis for much adult psychopathology. But how do we gain access to the thought processes of small children, whose verbal and introspective capacities are limited or non-existent? Klein’s great technical innovation was the introduction of play therapy. She pro-vided her little patients with play materials—paper and pencils, a doll house with ﬁ  gures, a sandpit, and farmyard animals—and

observed the pictures and games which the children set-up, making her interpretations around them. She used the methods of dream interpretation to formulate her ideas. What she observed in play—movement of ﬁ  gures in and out; bringing things together, often 
violently; separation and disruption—she took to represent the workings of the child’s mind. Still deeply inﬂ  uenced by drive theory, 
and by Freud’s insistence on the pre-eminence of sexuality and cas-
tration anxiety, she found sexual and aggressive meanings in all that was presented to her. Every vertical line or oriﬁ  ce-shaped circle 
drawn had a sexual signiﬁ  cance; every conjoining or emitted sound 
stood for parental intercourse, by which the child was both fasci-nated and frightened. Exploration and the drive to know were seen

307
as an expression of the desire to possess the mother’s body, and 
inhibitions of learning as manifestations of castration anxiety.
Here Klein began to depart from Freud. For him the Oedipus 
complex arose around the age of three, when the child begins to observe his or her parents’ relationship and to feel such emotions as passionate love, envy, fear, and jealous vengefulness. Klein, by contrast, saw Oedipal phenomena as arising much earlier in devel-opment. For example, the infant may experience weaning as a punishment or symbolic castration, and believe that his mother’s breast in his mouth has been displaced by the paternal penis in her vagina. Two other aspects of Kleinian thought emerge from this. First, in Klein’s schema the infant has an instinctual knowledge of the body and its relationships. There appears to be a reservoir of unconscious phantasy, which she saw as the mental accompani-
ment of bodily function: phantasies about the breast, the mouth,

ment of bodily function: phantasies about the breast, the mouth, 
the penis, the vagina, and their relationships that could not have arisen from direct observation, and therefore must be present from within, as correlates of the child’s bodily sensations, which Klein saw as dominating the early years of life. Unconscious phantasies are akin to Jungian archetypes or perhaps the ‘language acquisition devise’ postulated by linguists: preformed mental constructs unconsciously shaping experience and patterns of relationship.
Second, and closely related to unconscious phantasy, is the idea 
of internal objects—initially body parts, and later ‘whole objects’ that are salient to emotional life—the mother and her breast, the father and his penis, bellies and their contents such as unborn babies, faeces, and sphincters. These objects are endowed with motivational properties reﬂ  ecting the infant’s emotional life, which

Klein saw as dominated by persecutory fears. The ‘death instinct’ ensures that the child reacts to frustration with overwhelming feelings of hatred and destructiveness. These feelings are then pro-jected outwards on to the objects in the child’s emotional environ-ment, which are in turn reintrojected to populate the inner world. T o preserve good feelings from these terrifying bad objects, the child also projects goodness outwards. Thus a radical split arises between good and bad experiences, which are attributed to good and bad objects: ‘in the very earliest stage every unpleasant stimu-lus is related to the ‘bad’ , denying, persecuting breasts, every ‘good’ experience to the ‘good’ gratifying breasts’ .
(2)
Klein depicts early emotional life as dominated by the infant’s 
fears of annihilation from without, and the use of the mechanisms of splitting and projection to reduce these fears. She postulated the onset of a new type of anxiety towards the end of the ﬁ  rst year of

life. Here the infant is beginning to bring the image of the ‘good’ and the ‘bad’ breast together, and to realize that they are one and the same. With weaning, the child experiences his ﬁ  rst major loss. 
Now ‘depressive’ anxiety comes into the picture. The child believes that he is responsible for the loss, and that he has destroyed the good object with his aggression and sadism. He begins to feel guilt and remorse, and wants to repair the damage he believes he has inﬂ icted on his objects. His attempts at creation, the gifts he offers, 
and the charm with which he approaches his caregivers are all motivated by this sense of depressive despair and the wish to make 
reparation.
Klein thus described a developmental sequence: inherent aggres-
sion, annihilation anxiety, projection and splitting of the object into good and bad, loss, bringing together the split objects, depres-sive despair, concern for the object, and ﬁ  nally reparation. For

her this was a description of normal development, and she saw pathological states as resulting from developmental arrest along 
this line. The fulcrum of this sequence is the movement from what, drawing on Fairbairn’s term (see below) Klein now called the ‘paranoid–schizoid’ position  (PSP) to the ‘ depressive’ position’
(DP), a movement from splitting, blaming, and avoidance, to inte-
gration, responsibility, and concern for the object (see Hobson et al.
(4) for objective evidence of the validity of the PSP–DP distinc-
tion). Klein saw the struggle between PSP and DP as a lifelong process, an equilibrium driven one way or the other depending on life experience and constitutional endowment.
Klein was generally rather unconcerned about the impact of

Klein was generally rather unconcerned about the impact of 
external reality on psychological development (a point which, as we shall see, stimulated Bowlby’s divergence from her ideas). T o the extent that she did consider the real as opposed to the phantasized role of the parents, it was as benign ﬁ  gures whose job it is to miti-
gate the strength of the infant’s need to hate, project, and split. An important late theoretical contribution, however, concerned the role of envy in psychic life. One of the strengths of a psychoana-lytical approach to psychotherapy is that it takes seriously the phe-nomenon of resistance, and the fact that psychic growth is usually hard-won, often with much backsliding and self-defeatingness. 
With her emphasis on the dark side of human nature, Klein real-

ized that the infant may feel persecuted not just by frustration and separation, but also by the very capacity of the caregiver to satisfy his needs. The breast upon which the baby depends for satisfaction and pleasure can also be a source of envy and hatred in its pleni-tude and ability to create dependency. This envy  then becomes a 
basis for destructiveness within psychotherapy, and more generally: an explanation, perhaps, for the grafﬁ  ti which inevitably appear on 
beautiful buildings, or, at times, the fact that patients attack and seem to want to destroy the very help that is offered to them.
Another key Kleinian concept is that of projective identiﬁ  cation
(PI), a difﬁ  cult and perhaps misnamed concept, coined almost 
casually by Klein in an attempt to describe how parts of the ego may be split-off and projected not just on to  objects in the environ-

ment as visualized in Freud’s notion of projection, but into them. 
As originally conceived by Klein PI referred to the solipsistic world of the infant described above, in which unbearable feelings of rage and hatred are split-off, projected into the breast, which is then perceived by the child as ‘having’ properties that in fact originated in the self. Projective identiﬁ  cation here is a form of misperception

or delusional perception, which can be used both to explain the fact that normal adults’ experience of the world is inevitably col-oured by their emotional state (the gloomy or rose-tinted specta-cles with which we view the world), and to account for delusional ideas in psychosis, such as paranoid feelings of persecution which, it is hypothesized, originate in the subject’s own aggressive phanta-sies but are attributed, via projective identiﬁ  cation, to persecutors.
Projective identiﬁ  cation differs from simple projection in that 
the objects of PI are induced or controlled by the projection in such a way that they then enact  the phantasy, which has been transferred 
into them. Paranoid people have the capacity to make those around them behave in suspicious or hostile ways, and thus projective identiﬁ  cation can be thought of as a form of communication in

into them. Paranoid people have the capacity to make those around them behave in suspicious or hostile ways, and thus projective identiﬁ  cation can be thought of as a form of communication in 
which the recipient of the projection is induced to think or feel in ways that properly ‘belong’ to the projector. Post-Kleinian authors, notably Bion,
(5) Heimann,(6) and Ogden,(7) have extended the con-
cept of projective identiﬁ  cation, with an emp hasis on this commu-
nicative aspect, in that PI requires a recipient as well as a projector.3.2 object relations, attachment theory, self-psychology, and interpersonal psychoanalysis

SECTION 3  psychodynamic contributions to psychiatry 308
Bion , an analysand of Klein, realized that projective identiﬁ  ca-
tion also underlies normal empathy and fellow feeling. PI is 
‘primitive’ in the sense that preverbal children rely on it almost exclusively to communicate their feelings, but this denotes immaturity rather than pathology. Bion went on to develop his container-contained  theory of early emotional communication. 
Here the mother, or ‘breast’ , acts, via PI, as a recipient or container for the infant’s unmanageable feelings of fear, hatred, annihilation, etc. These feelings are contained or held by the mother, and ‘detoxiﬁ  ed’ before they are ‘returned’ to the infant through her 
understanding and empathic handling. She knows intuitively—through projective identiﬁ  cation—when her child cries whether it

understanding and empathic handling. She knows intuitively—through projective identiﬁ  cation—when her child cries whether it 
is hungry or cold, or bored or wet, etc., and responds appropriately. In this way the infant begins to build-up a sense of himself through thereﬂ ective awareness  of the mother. Disruptions of this process, 
for example through maternal depression or the violent use by the parent of the infant as a container ( role reversal ) as occurs in child 
abuse, may sow the seeds of disorders of identity found in border-line personality disorder in later life.
PI is important in the contemporary understanding of counter-
transference . Paula Heimann pointed out that the therapist’s 
reactions to the patient, while no doubt coloured to some extent by her own conﬂ  icts (Freud’s classical conceptualization of counter-
transference), also represent feelings induced by contact with the patient, that is to say they are a manifestation of projective identiﬁ  -

cation. By attending to these thoughts and feelings the therapist gains clues about the patient’s state of mind, which can then be put into words as interpretations. Here the therapist’s mind is the 
container for the patient’s split-off feelings. Sometimes this 
container-contained relationship fails, and the therapist is induced to enact some aspect of the patient’s inner world, for instance by forgetting an appointment with a patient who has felt neglected and overlooked as a child, or by expressing anger or boredom in his tone of voice, being himself moved by feelings which properly belong to the patient.
The ﬁ  rm boundaries of psychotherapy are, in part, designed to 
minimize these occurrences (although they are unavoidable, and often, if reﬂ  ected on, can be put to good use in the form of deep-

ened understanding), but in the much more uncontained setting of general psychiatric wards or community mental health centres such enactments are widespread. A common example would be the polarization which disturbed people with borderline personality disorder can induce in their carers, some seeing the patient as manipulative and demanding, others feeling intense sympathy, and the wish to repair past hurts on the patient’s behalf. Each perspec-tive represents a split-off aspect of the patient’s inner world that has been picked up via PI by different staff members. This is an essentially interactive process, since, no doubt, what determines which aspect depends on the carers’ own developmental history and defensive strategies.
Working in the relative isolation of Scotland, and coming to

Working in the relative isolation of Scotland, and coming to 
essentially similar conclusions to Klein about the importance of splitting, W.R.D. Fairbairn
(8) further developed this interpersonal 
perspective. For him drives were ‘a signpost to the object’ , the glue that held human beings together. Sex is what gets us close to those who matter, rather than vice versa, as originally conceived by Freud. Like Bion later, Fairbairn also placed great emphasis on the role of the mother and of environmental failure as a source of psychopa-thology. Frustration plays a central part in his schema. With a perfectly responsive mother, the child has no need to think or 
develop an inner world. When separation and frustration come into play, the child then builds up an image of the object, which is split into three parts: the ideal object  (one that would never cause 
frustration), the libidinal object  (one that could satisfy the child’s

frustration), the libidinal object  (one that could satisfy the child’s 
drive-related needs), and the anti-libidinal object  (the one that 
frustrates). This in turn sets up a split of the self into three corre-sponding parts—ideal self, libidinal self, and anti-libidinal self. The Fairbairnian model provides clarity in understanding some typical phenomena found in severe personality disturbance: the swing between idealization and denigration of therapists and partners (who become the anti-libidinal withholding object at that point), the self-destructiveness of the anti-libidinal self, or ‘internal saboteur’ , and the split-off search for pure libidinal satis-faction unrelated to persons represented by substance abuse and 
promiscuity.
Fairbairn’s notion of schizoid withdrawal was conceptualized 
as a typical interpersonal strategy in the face of frustration. John Steiner
(9) has developed a similar idea in his notion of the psychic

(9) has developed a similar idea in his notion of the psychic 
retreat, an inner place to which individuals with borderline person-ality may repair in the face of environmental trauma, and which may make them relatively inaccessible in therapy. Another impor-tant neo-Kleinian development has been Ronald Britton’s
(10)

(10)
attempt to link the Oedipus complex with the tolerance of sepa-rateness and loss implicit in the depressive position. Britton sees the ability, at times, to let go of the mother as the Oedipal stage is successfully negotiated—in which the child comes to see that his mother and father are sexually involved with one another and he is necessarily excluded—as an important developmental step towards the establishment of an inner world and the ability to see things from varying perspectives. This can be linked with Bion’s idea of creative thought in which ideas are brought together to create ‘conceptions’ , in contrast to the destructiveness of schizoid thinking in which, as a way of reducing anxiety, the links between things and ideas are attacked, and the world emptied of meaning. The restoration of meaning is a central task of psychotherapy. The 
dialectic of close involvement and repeated separation inherent in

dialectic of close involvement and repeated separation inherent in 
the therapeutic relationship fosters this capacity, enabling disturbed patients ﬁ  rst to ﬁ nd their experience mirrored  by the responsive 
therapist, then gradually to tolerate loss and envy , and so to gain 
the capacity to think and to feel more autonomously.
Object relations 2: Balint and Winnicott
The ‘Object relations’ school of psychoanalysis is a broad church. Klein’s view of the mind and of psychopathology was essentially a conﬂ  ictual  model: difﬁ  culty arises out of the inherent conﬂ  ict in 
an immature mind between love and hate, and attempts to avoid the inevitability of loss. For her, such conﬂ  ict was characteristic of 
normal development, and pathology merely an exaggeration of normal conﬂ  ict in which the environment has failed to mitigate its

normal development, and pathology merely an exaggeration of normal conﬂ  ict in which the environment has failed to mitigate its 
potentially destructive effects. By contrast, the non-Kleinian mem-bers of the ‘object relations’ school tend to espouse some variety of adeﬁ cit model, in which normal and abnormal development are 
more sharply differentiated, and the basis for psychopathology is a failure of the environment to provide the conditions needed for healthy psychic growth.
Michael Balint
(11) is perhaps best known for his work in raising 
psychological awareness among general practitioners through the

309
use of ‘Balint groups’ , but he was also a signiﬁ  cant ﬁ  gure in psy-
choanalysis, introducing a number of key terms and concepts. In 
contrast to Klein, who saw the newborn infant as wracked with fear and conﬂ  ict, Balint proposed a state of primary love  characterizing 
the early mother–infant relationship—which he described as a ‘har-
monious interpenetrative mix-up’ . Where, however, parenting was 
inadequate, due to neglect, overintrusiveness, aggression, or abuse he claimed that the child would be permanently scarred at the level of the ‘ basic fault ’ . His model of therapy implied a 
remedial , rather than purely interpretative  approach, with the

remedial , rather than purely interpretative  approach, with the 
therapist’s role including both quiet acceptance, and on occasion therapeutic ‘acting in’: Balint would sometimes gently hold the patient’s hand, and, famously, once encouraged a patient who stat-ed that she had never had the courage to do a somersault to try one out in the consulting room then and there (behaviour therapy meets psychoanalysis!).
Donald Winnicott,
(12) visualized an intermediate zone in the 
early years of life that was neither the realm of pure phantasy (as described by Klein), nor that of reality (to which adaptation by the ego was required, as described by Freud), although it partakes of both. In this intermediate, or transitional  zone the infant learns,

with the help of the mother, to play (another key Winnicottian theme). Here phantasies can become reality, at least for the dura-tion of the interactive play. In this transitional space Winnicott saw the origins of creativity and culture generally, and of a nascent sense of self. He suggested that the mother’s face is a kind of mirror in which the child sees his own feelings reﬂ  ected, and through this 
recognition begins to gain a sense of who he is. This process is disrupted if the mother is depressed or abusive, and here perhaps are the germs of borderline personality disorder, characterized by a 
deﬁ cient sense of self, and feelings of inner emptiness and sterility. 
Winnicott saw ‘learning to play’ as a key task in therapy in helping patients to regain their sense of self.
A related phenomenon is that of the transitional object —the

A related phenomenon is that of the transitional object —the 
special handkerchiefs, teddy bears, and precious playthings that toddlers often need for comfort and to help them sleep. Winnicott saw these as buffers against loss, objects that are invested with the properties of the primary object (the mother and her breast) but remain under the control of the child. They are ‘transitional’ in the sense that they lie between the ideal object of phantasy and the real, but potentially unreliable, objects of external reality.
The subtlety of Winnicott’s thought is exemplified by his 
notion of the good-enough mother . Unlike some psychoanalytical

notion of the good-enough mother . Unlike some psychoanalytical 
writers he did not attribute all the evils of mankind to parental failure. Winnicott realized that a ‘perfect’ mother, intrusively aware of her infant’s needs could inhibit rather than foster the develop-ment of a sense of oneself as a separate and autonomous being. Mothers (and presumably fathers) should be ‘good enough’ , not perfect, not least because through healthy protest about parental failure the child learns his own strength and ﬁ  nds limits, which 
reassure him that his parents can withstand his aggression and still love him.
Winnicott realized that developmental deﬁ  cit does not always 
take the form of neglect or overt violence. He noticed the ways in which parents, driven by their own unconscious needs, may subtly impose their will on a compliant child, thereby inhibiting the growth of a robust and distinct sense of self. The false-self-real-self

distinction tries to capture the ways in which children, and later personality disordered adults, may present an acceptable face to the world that is radically at variance with inner feelings of terror, 
emptiness, or rage. In his seminal, but today largely forgotten, classic The Divided Self , R.D. Laing
(13) took Winnicott’s false-self-
real-self distinction as a central theme in his psychodynamic account of schizophrenia, seeing delusions as representing a way of holding together, albeit ‘falsely’ , a disintegrating ‘real’ self and its inner world.
John Bowlby and attachment theory
Winnicott’s contemporary John Bowlby(14) life’s work was an 
attempt to bring logical and scientiﬁ  c rigour to psychoanalytical 
thought. Attachment theory, an empirically validated version of object relations theory, starts from Freud’s
(15) revised theory of 
anxiety, in which, rather than viewing it as the result of incomplete repression of incestual wishes, anxiety is conceptualized in inter-

personal terms as a response to the threat of the loss of a loved one. Based on his observations of delinquent youths, many of 
whom had suffered the loss of a parent during early childhood, and the depressive reactions of small children to separation from their parents on entering hospital, Bowlby saw that protection from dan-ger was a key component of the parent–child relationship, and that there were built-in psychological mechanisms to ensure the main-tenance of attachment bonds.
Attachment theory
(16) postulates that, when faced with threat, 
illness, or exhaustion, children will seek proximity to their caregiv-ers, or ‘ secure base ’ . A protective response from the caregiver

illness, or exhaustion, children will seek proximity to their caregiv-ers, or ‘ secure base ’ . A protective response from the caregiver 
assuages the child’s attachment needs, who can then return to play or exploratory behaviour, secure in the knowledge that help will once more be at hand if needed. This provides the conditions for secure attachment , and the child builds up an internal working 
model  (Bowlby’s preferred term for the inner world) of a secure 
robust self and responsive others.
Secure attachment arises out of responsive and sensitive 
parenting  and is contrasted with insecure attachment , which 
Bowlby saw as a factor predisposing to adult neurosis. Bowlby’s collaborator, Mary Ainsworth, and her students, have researched different patterns of insecure attachment and the conditions under 
which they arise.
(17) They delineate three main types of insecure 
attachment: insecure-avoidant, insecure-ambivalent, and

attachment: insecure-avoidant, insecure-ambivalent, and 
insecure-disorganized . The avoidant child has experienced 
brusque or aggressive parenting, and tends to avoid close contact with people, hovering near caregivers rather than openly express-ing need when faced with threat. The ambivalent child clings to his inconsistent parents, and ﬁ  nds exploratory play difﬁ  cult, even 
when the danger has past. Disorganized children behave in bizarre ways when threatened, and tend to have parents who are either emotionally intrusive or absent, often in the context of a parental history of abuse in their childhood. Disorganization is thought to be a severe form of insecure attachment and a possible precursor of severe personality disorder and dissociative phenomena in adolescence and early adulthood.
Mary Main
(18) has developed a psychodynamic interview 
schedule, the Adult Attachment Interview ( AAI), which is rated for

Mary Main
schedule, the Adult Attachment Interview ( AAI), which is rated for 
the interviewee’s narrative style, and, in long-term follow-up stud-
ies of children whose attachment patterns have been classiﬁ  ed in 
infancy, yields signiﬁ  cant links with these earlier patterns of attach-
ment. As with response to threat in childhood, adults’ ways of talking about themselves and their lives vary enormously. Some, in 3.2 object relations, attachment theory, self-psychology, and interpersonal psychoanalysis

SECTION 3  psychodynamic contributions to psychiatry 310
the secure-autonomous  style, talk freely about themselves and 
their past pain in a coherent and apposite way. The insecure-
dismissive  style minimizes problems and is characterized by 
unelaborated speech lacking in metaphor or vividness. The insecure-
preoccupied  style is rambling and emotionally laden, while an 
insecure-unresolved  pattern has evident breaks in continuity and 
logical ﬂ  ow. These insecure speech patterns are, it is suggested, 
manifestations of the underlying psychobiological relational dis-positions, which the various theories of object relations attempt to capture. The way we speak about ourselves reveals the state of our inner world. Peter Fonagy
(19) has suggested that the capacity to 
represent experience, which he calls reﬂ exive function , (a contem-

porary version of the classical psychoanalytic notion of ‘insight’), is a buffer against psychiatric disturbance. Once pain is represented in the mind the sufferer can distance himself from it, and consider alternative ways of responding. Enhancement of reﬂ  exive function 
is a generic psychotherapeutic strategy and applies as much to cognitive therapy (becoming aware of negative cognitions and automatic thoughts) as psychodynamic therapies.
Bowlby objected to what he saw as the hijacking of the term 
‘biological’ by organic psychiatry, since he believed the attachment relationship and its vicissitudes, adaptively shaped by evolutionary pressures, was no less ‘biological’ than the neurochemistry which presumably mediates it. For him human psychology was funda-mentally relational. He saw attachment needs as existing through-

out the life cycle, and put separation and loss as central to his view of the origins of psychiatric disturbance. In the attachment model, separation from a caregiver is a threat: we are biologically pro-
grammed to respond with shock, denial, anger, and searching behaviours when separated from a loved person or object. Loss is an irrevocable separation, and the early phases of the bereavement response are all vain attempts to restore the status quo. Despair and depression come with the recognition that separation is ﬁ  nal, 
and, beyond that, reorganization of internal working models, the recognition that although the loved one is lost in reality, good memories live on in the inner world.
The attachment perspective has implications for the day-to-day

The attachment perspective has implications for the day-to-day 
practice of psychiatry. One function of the psychiatric facilities and of mental health workers is to provide the patient with a ‘secure base’ , which in itself goes some way to reducing anxiety. Appropriate dependency is integral to the supportive psychotherapeutic relationship, which is such a key part of the psychotherapeutic dimension of psychiatry. Short-term, unresponsive, or rejecting relationships with psychiatrists and other mental health workers reinforce insecure attachment and may lead patients to redouble their efforts to cling on to the psychiatric institution—an all too familiar vicious circle.
The ego and its defences: Anna Freud, 
Hartmann, and Lacan
The role of the ego and of defence mechanisms was a particular 
concern of Anna Freud,(20) who represented a parallel tendency to

concern of Anna Freud,(20) who represented a parallel tendency to 
the object relations school. She elaborated a taxonomy of defences used by the ego to maintain its integrity in the face of both internal threat from the id, and the demands and impingements of external reality. Valliant
(21) groups Anna Freud’s defences into those that are 
immature  (like projective identiﬁ  cation and splitting), neurotic 
defences  (which include intellectualization, reaction formation, and identiﬁ  cation with the aggressor), and mature  ones (such as 
humour and sublimation).
Reaction formation  describes the ways in which the ego 
counteracts unconscious desires or impulses that threaten its equilibrium by consciously held views directly contrary to these: the militant paciﬁ  st who is out of touch with any feelings of aggres-

sion for example. Identiﬁ  cation with the aggressor  is frequently 
invoked in discussions of the psychological effects of childhood abuse. One way of dealing with the horr or of abuse is to  ‘dis-iden tify’ 
with oneself (a form of dissociation), and to put oneself in the place of the person who is attacking, thereby reducing feelings of pain and helplessness. This idea helps to explain how those who have been abused in childhood may become abusers themselves in adult life. A frequent experience in working with severely disturbed patients, many of whom are abuse survivors, is that health care workers may themselves feel attacked or symbolically ‘abused’ by these patients—seeing how the patient may have unconsciously identiﬁ  ed with their aggressor can help carers to a greater under-

standing of their patients’ problems and to respond less defensively to these attacks.
Valliant has found that men who use more mature defence 
mechanisms are less vulnerable to physical and psychological ill-ness, and an important aim of psychotherapy would be to help the patient move from the use of more- to less-primitive defence mechanisms. Defences are therefore legitimately seen as adaptive, and, from a developmental perspective, the earlier the presumed psychic trauma, the more likely are primitive defence mechanisms to be employed.
David Malan’s
(22) triangular model  of anxiety, defence, and 
‘hidden impulse’ is another variety of ego psychology, which has found favour in psychiatric circles. It provides a clear formula for thinking about neurotic difﬁ  culties: for example people suffering

from agoraphobia commonly defend against anxiety by avoidance and dependency; underlying this there may be hidden feelings of dissatisfaction and aggression, immediately towards a spouse, and in the past towards a controlling but unaffectionate mother. For Malan, the task of therapy is to allow the ego to tolerate and express the hidden feelings; note that cognitive therapy (q.v.) similarly helps the patient to become aware of and then counteract the automatic thoughts (equivalent to hidden feelings) that undermine the ego’s attempts to achieve conﬂ  ict-free functioning.
The self, meaning, and interpersonal 
psychoanalysis: Sullivan, Horney, and Kohut
Freud’s models of the mind were essentially intrapsychic, and 
couched in quasi-scientiﬁ  c language. Object relations retained this 
perspective but introduced a relational dimension never fully developed by Freud. Interpersonal psychoanalysis  in the United

perspective but introduced a relational dimension never fully developed by Freud. Interpersonal psychoanalysis  in the United 
States was even more radically interpersonal than object relations. Harry Stack Sullivan
(23) was a free thinker who emphasized this 
existential aspect of psychotherapy, while remaining within the psychoanalytical tradition. He worked particularly with people suffering from schizophrenia. Sullivan believed in close involve-ment with his psychotic patients. His mission was always to ﬁ  nd 
meaning in their experience, rather than dismiss it as an unintelli-gible manifestation of organic illness. He was a major inﬂ  uence on 
a generation of psychoanalytically informed psychiatrists including Harold Searles , Freida Fromm-Reichman , and Karen Horney.
(24)

311
The latter, like Sullivan, was critical of the patriarchal bias 
of psychoanalysis. For her, castration complex and penis envy were 
social rather than biological phenomena, manifestations of social relations that subjugated women, and from which, by appropriate action, including psychotherapy, they could be liberated. Horney’s contemporary, Eric Fromm , brought a Marxist inﬂ  uence into 
psychoanalysis, emphasizing the part played by capitalist produc-tion methods in contributing to isolation and anomie of modern men and women and their psychological troubles.
Although conventional psychoanalytical treatment for schizo-

phrenia is now largely discredited, there is increasing interest in the role of psychosocial interventions in psychosis. Here the Sullivanian principles of respect for the patient’s experience and its meaning, the need for a long-term supportive psychotherapeutic relation-ship, attention to the social precipitants of psychosis, and a focus on the ways in which the therapist may, through countertransfer-ence, foster recovery or reinforce pathology, are all highly relevant to contemporary psychiatry.
Heinz Kohut
(25) was concerned not so much with schizophrenia, 
but with that intermediate world between neurosis and psychosis which psychoanalysts call ‘borderline’ pathology, and which has entered the DSM as Borderline Personality Disorder. Like Sullivan, Kohut puts self-esteem and its disorders  at the centre of his psy-

chology, seeing the origins of self-esteem in the empathic respon-siveness of caregivers in the early years of life. For him there is a core of healthy narcissism , which is based on the grandiosity and 
omnipotence of the young child (‘his majesty the baby’ , as Freud put it), which is both accepted and fostered by effective parenting. Parents at this stage are ‘ self-objects ’ , a concept akin to Winnicott’s 
transitional objects, who partake both of the self and of the respon-sive environment, and which the infant believes, in his state of healthy delusion, to be there exclusively for his beneﬁ  t.
Like Winnicott, Kohut emphasizes ‘mirroring’ as a key interper-
sonal theme. For Winnicott parental mirroring helps the child to 
own his emotions and begin to know who he is. Kohut, by contrast, takes up the narcissistic aspect of the mirror: the child sees his reﬂ ected glory in the eyes of his admiring parents, and this contrib-

utes towards his own positive self-regard. As development proceeds there is a process of ‘optimal disillusionment’ , similar to the resolu-tion of the Oedipus complex, in which the child gradually learns that his objects have a life of their own. By this time, however, his sense of a valued and effective self will be sufﬁ  ciently developed, 
and residual narcissism will serve the useful functions of ambition, aspiration to success and admiration, a sense of duty and concern for others, and the capacity to invest in ones offspring.
Where the environment is unempathic, mirroring is deﬁ  cient,

Where the environment is unempathic, mirroring is deﬁ  cient, 
fragile grandiosity squashed, or disillusionment traumatic, the stage is set for borderline pathology, in which self-absorption, and the use of others as self-objects, appropriate to the infantile years, persists into adult life. Self-injurious behaviour such as drug abuse, eating disorders, and deliberate self-harm are ‘breakdown products’ of a disintegrated self, trying to use the environment as a self-object that will provide momentary and illusory satisfaction and self-afﬁ  rmation.
A therapeutic implication of Kohut’s approach is that the thera-
pist is more supportive than in classical analysis, tolerant of the patient’s grandiose designs, especially in the early stages of treat-ment. This contrasts with the approach of Otto Kernberg
(26) who 
synthesizes classical and Kleinian concepts, and advocates rigorous interpretation, especially of destructive and self-defeating behaviour

(26) who 
synthesizes classical and Kleinian concepts, and advocates rigorous interpretation, especially of destructive and self-defeating behaviour 
in borderline patients. Kohut’s and Kernberg’s theories reﬂ  ect the 
typical polarization that such patients evoke in clinical settings, perhaps mirroring an inner world rigidly split into good and bad objects. Effective treatment requires a synthesis: empathy and tol-erance is needed to form a working alliance, but ﬁ  rm limit-setting 
and confrontation of destructiveness is also essential. Another inter-personal synthesis is to be found in the work of Stephen Mitchell
(27)
whose approach reminds the therapist of the reci procity of the therapeutic relationship in what Robert Lang calls the ‘bipersonal ﬁ eld’: patient and therapist form a system of mutual inﬂ  uence, the 
job of the therapist being both to participate in this, and at the same time to be sufﬁ  ciently detached to be able to reﬂ  ect upon it.

The shift in interpersonal psychoanalysis away from the analyst 
as an objective and privileged observer to a co-participant has given rise to a contemporary interest in narrative or hermeneutic explanations in psychotherapy,
(28) in contrast to the scientiﬁ  c psy-

chology, which Freud originally hoped to establish. These authors argue the case for psychoanalysis as a hermeneutic discipline whose aim is to explore meaning rather than objective truth. If Freud is one of the intellectual founding fathers of modernism, their approach is ‘postmodern’ in the sense that it stresses the rela-tivism of values and meanings, and the importance of power in determining one’s view of the world. Here is a link—albeit so far rather distant—with the emerging ‘user’ movement in psychiatry, and the importance of giving as much weight to the client’s voice as to that of the professional. Psychological truths are inherently contextual, and without awareness of the social context they can be obfuscatory.

Many new perspectives have emerged in the century since psychoa-nalysis was conceived. Emphasis has shifted from the intrapsychic to the interpersonal. Kleinian psychoanalysis offers a unique vision of the ways in which interpersonal reality is inescapably coloured by the emotional state of the participants. Attachment theory pro-vides an account of human psychological development that both takes account of meaning and is empirically based. Psychoanalysis is emerging from its isolation and bridges have begun to be built with cognitive science: the inner world of phantasy is not unlike the world of schemata and assumptions that are the focus of cognitive therapy. There are, through modern neuroimaging techniques links to be forged with neurobiology: the impact of effective therapeutic interventions on brain architecture can now be visualized. Progress will depend on further theoretical syntheses and technological

advances, while holding ﬁ  rm to the humanistic emphasis on perso nal 
meaning and inner experience that is the fundamental contribution of psychoanalysis to contemporary psychiatry.
Bateman, A. and Holmes, J. (1995). Introduction to psychoanalysis: 
contemporary theory and practice . Routledge, London.
Cassidy, J. and Shaver, P . (eds.) (2007). Handbook of attachment  (2nd edn). 
Guilford, New Y ork.
Fonagy, P . and Target, M. (2002). Psychoanalytic theories. Perspectives from 
developmental psychopathology . Whurr, London.
Gabbard, G., Beck, J., and Holmes, J. (2005). Oxford textbook 
of psychotherapy . Oxford University Press, Oxford.3.2 object relations, attachment theory, self-psychology, and interpersonal psychoanalysis

SECTION 3  psychodynamic contributions to psychiatry 312
Mayes, L., Fonagy, P ., and Target, M. (eds.) (2007). Developmental science 
and psychoanalysis . Karnac, London.
 1. Freud, S. (1917). Mourning and melancholia. In Standard edition of the 
complete psychological works of Sigmund Freud , Vol. 14 (ed. J. Strachey), 
pp. 239–58. Hogarth Press, London, 1957.
 2. Klein, M. (1986). The selected Melanie Klein  (ed. J. Mitchell). Penguin, 
 3. Spillius, E. (1988). Melanie Klein today . Routledge, London.
 4. Hobson, R.P ., Patrick, M., and Valentine, J. (1998). Objectivity in 
psychoanalytic judgements. The British Journal of Psychiatry ,173,
172–7.
 5. Bion, W. (1988).  Attacks on linking. In Melanie Klein today  (ed. 
E. Spillius), pp. 178–86. Routledge, London.
 6. Heimann, P . (1950). On countertransference. International Journal of 
Psychoanalysis ,31, 81–4.
 7. Ogden, T. (1979). On projective identiﬁ  cation. International Journal of

6. Heimann, P . (1950). On countertransference. International Journal of 
 7. Ogden, T. (1979). On projective identiﬁ  cation. International Journal of 
Psychoanalysis ,60, 357–73.
 8. Fairbairn, W.R. (1952). Psychoanalytic studies of the personality .
 9. Steiner, J. (1993). Psychic retreats . Routledge, London.
10. Britton, R., Feldman, M., and O’Shaughnessy, E. (1989). The Oedipus 
complex todsay. Karnac Press, London. 
11. Balint, M. (1968). The basic fault . Tavistock Press, London.
12. Winnicott, D. (1971). Playing and reality . Penguin, Harmondsworth.
13. Laing, R. (1961). The divided self . Penguin, Harmondsworth.
14. Bowlby, J. (1988). A secure base: clinical applications of attachment 
theory . Routledge, London.15. Freud, S. (1926). Inhibitions, symptoms, and anxiety. In Standard 
edition of the complete psychological works of Sigmund Freud , Vol. 20 
(ed. J. Strachey). Hogarth Press, London.

16. Cassidy, J. and Shaver, P . (eds.) (2007). Handbook of attachment
(2nd edn). Guilford, New Y ork.
17. Holmes, J. (2001). The search for the secure base: attachment theory 
and psychotherapy. Routledge, London.
18. Main, M. (1995). In Attachment theory: social, development and clinical 
perspective  (eds. S. Goldbery, R. Muir and J. Kerr), pp. 407–74. Analytic 
Press. New Y ork.
19. Fonagy, P . (1995). In Attachment theory: social, development and 
clinical perspective (eds S. Goldbery, R. Muir and J. Kerr), pp. 233–78. Analytic Press. New Y ork.
20. Freud, A. (1936). The ego and the mechanisms of defense . Hogarth Press, 
London.
21. Valliant, G. (1992). Ego mechanisms of defense: a guide for clinicians and 
researchers . American Psychiatric Press, Washington, DC.
22. Malan, D. and Coughlin Della Selva, P . (2006). Lives transformed .
Karnac, London.

23. Sullivan, H.S. (1962). Schizophrenia as a human process.  Norton, 
New Y ork.
24. Horney, K. (1939). New ways in psychoanalysis.  Norton, New Y ork.
25. Kohut, H. (1977). The restoration of the self . International Universities 
26. Kernberg, O. (1996). A psychoanalytic theory of personality disorders. 
In Major theories of personality disorder
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M. Lenzenweger), pp. 116–137. Guilford Press, New Y ork.
27. Mitchell, S. (1988). Relational concepts in psychoanalysis: an integration .
Harvard Universities Press, Cambridge, MA.
28. Roberts, G. and Holmes, J. (eds.) (1998). Healing stories: narrative in 
psychiatry and psychotherapy . Oxford University Press, Oxford.

3.3
Current psychodynamic 
approaches to psychiatry
Psychodynamic psychiatry is broadly deﬁ  ned today. In fact, the 
term psychodynamic is now used almost synonymously with psychoanalytical. Freud originally used the term psychodynamic to emphasize the conﬂ  ict between opposing intrapsychic forces: a 
wish was opposed by a defence, and different intrapsychic agencies, such as ego, id, and superego, were in conﬂ  ict with one another. 
Indeed, for much of the twentieth century psychoanalytical theory was dominated by the drive-defence model, often referred to as ego psychology.
In the last decades of the twentieth century, however, psychoana-
lytical theory expanded beyond the notion of conﬂ  ict among 
intrapsychic agencies. Internal object relations became paramount in models deriving from these sources. In addition, a deﬁ  cit model

intrapsychic agencies. Internal object relations became paramount in models deriving from these sources. In addition, a deﬁ  cit model 
of symptomatology arose from the work of the British object-relation theorists, such as Balint and Winnicott. In the United States, Kohut’s self-psychology also developed a model based on developmental deﬁ  cits. In other words, disturbed patients who 
came to treatment were seen as suffering from absent or weakened psychic structures based on developmental failures by parents or caretakers in the early childhood environment. (See Chapter 3.1 for an account of the development and modern practice of psychoanalysis.)
The typical psychodynamic psychiatrist then uses multiple mod-
els to assist in the understanding of a particular patient. 
Developments in neuroscience must also be taken into account. Moreover, the diagnostic and treatment approach to an individual

Developments in neuroscience must also be taken into account. Moreover, the diagnostic and treatment approach to an individual 
patient is psychodynamically informed even when a decision has been made to forego psychodynamic psychotherapy. Psychodynamic thinking provides a conceptual framework within which all treatments are prescribed, including pharmacotherapy, psycho-therapy, inpatient or partial hospital treatment, and group or family modalities. Psychodynamic psychiatry is not synonymous with psychodynamic psychotherapy.
A comprehensive definition of current psychodynamic 
psychiatry is the following:
(1)
Psychodynamic psychiatry is an approach to diagnosis and 
treatment characterized by a way of thinking about both patient and clinician that includes unconscious conﬂ  ict, deﬁ  cits, and dis-

(1)
tortions of intrapsychic structures, and internal object relations, and that integrates these element with contemporary ﬁ  ndings from 
the neurosciences.Basic principles
A set of time-honoured basic principles, all derived from psycho-analytical technique and theory, deﬁ  ne the overall approach of the 
dynamic psychiatrists (Table 3.3.1).
The unconscious
A fundamental premise of psychodynamic psychiatry is that mental activity going on outside our awareness can be profoundly inﬂ uential. Freud saw signs of the unconscious in two major types

A fundamental premise of psychodynamic psychiatry is that mental activity going on outside our awareness can be profoundly inﬂ uential. Freud saw signs of the unconscious in two major types 
of clinical evidence: parapraxes and dreams. Parapraxes, commonly referred to as slips of the tongue or ‘Freudian slips’ , involve substi-tuting one word for another. For example, a patient who intends to say ‘Protestant’ , may unwittingly say ‘prostitute’ . Parapraxes may also involve actions, such as forgetting, or executing one action when intending to do another.
Freud regarded dreams as the ‘Royal Road’ to the understanding 
of the unconscious. Another primary way that the unconscious manifests itself in the clinical setting is the patient’s behaviour toward the clinician. Certain characteristic patterns of relatedness to others set in childhood become internalized and are manifested 
automatically and unconsciously as part of the patient’s character.

automatically and unconsciously as part of the patient’s character. 
Hence certain patients may consistently act deferentially toward the clinician, while others will behave in a highly rebellious way. This type of procedural memory is closely linked to Squire’s
(2)
notion of implicit memory, which occurs outside the realm of verbal narrative memory.
While declarative or autobiographical memory involves 
remembered events and narratives of one’s life, procedural memory 
Table  3.3.1  Basic principles of psychodynamic psychiatry
Psychic determinism
Developmental orientation
Emphasis on the uniqueness of the individual 
rather than how the individual is like others
Transference
Countertransference
Resistance

SECTION 3  psychodynamic contributions to psychiatry 314
stores the ‘how’ of executing sequences of actions, such as motor 
skills. Once guitar-playing or bicycle-riding has been mastered, no conscious recall is necessary when one sits down with a guitar or jumps on a bicycle. The schema referred to as unconscious internal object relations are to some extent procedural memories repeated again and again in a variety of interpersonal situations. They are non-conscious, but not dynamically unconscious, in the sense of being defensively banished from conscious awareness.
The notion that much of mental life is unconscious is one 
that is often challenged by psychoanalytical critics, but it is also one that is extensively validated by literature from experimental psychology.
(3) Repression of memory has even been demonstrated 
in fMRI research.(4) The active effort to ‘forget’ unwanted past

in fMRI research.(4) The active effort to ‘forget’ unwanted past 
experiences involves a novel form of reciprocal interaction between the prefrontal cortex and the hippocampus. When subjects control unwanted memories, there is increased dorsolateral prefrontal activation associated with reduced hippocampal activation. The magnitude of forgetting is predicted by prefrontal, cortical, and right hippocampal activations.
The notion of psychic determinism is intimately linked with the construct of the unconscious. Freud felt that behaviour and mental life were related to multiple and complex causation.
(5) The term 
overdetermination implies that a variety of intrapsychic and unconscious factors come together to produce speciﬁ  c symptoms

overdetermination implies that a variety of intrapsychic and unconscious factors come together to produce speciﬁ  c symptoms 
or behaviours. The notion of multiple causation implies that there can be alternate sets of sufficient conditions, some involving primarily unconscious conﬂ  icting forces, others stemming from 
biological and environmental inﬂ  uences that ultimately produce 
similar symptoms or behaviours.
Regardless of which psychoanalytical theory seems to ﬁ  t best with a particular patient, the dynamic psychiatrist always thinks in terms of developmental models. Patterns of relatedness estab-lished in childhood are repeated in adult relationships. Modern dynamic psychiatrists avoid the early psychoanalytical reduction-ism that attempted to link an adult psychopathological syndrome to a speciﬁ  c developmental arrest or ﬁ  xation in childhood. T oday, 
full account is taken of genetic contributions to personality and

full account is taken of genetic contributions to personality and 
to psychiatric disorders. Environmental inﬂ  uences and genetic 
factors interact with one another reciprocally to shape the human 
being in health and illness. Still, the wisdom of the psychodynamic approach is that within each of us is a child yearning to complete 
some unﬁ  nished business from earlier in life.
Emphasis on the uniqueness of the individual
In much of descriptive psychiatry the major focus is on taxono-
my—speciﬁ  cally: How do groups of patients ﬁ  t together under one 
classiﬁ  cation? In psychodynamic psychiatry, by contrast, there is 
great interest in how a particular patient is unique—in other words, different from others. The subjective experience of the individual has been forged through an idiosyncratic narrative that is different from all other life stories and involves a speciﬁ  c interaction between 
genetic predisposition, intrapsychic factors, and environmental inﬂ uence.Transference

Intrinsic to the developmental model of mental organization is 
that adults are constantly repeating childhood patterns in the present. Transference is the best-known example of this phenome-non. The patient unconsciously experiences the doctor as a sig-niﬁ cant ﬁ  gure from the past and reacts to the doctor based on a 
set of unconscious attributions based on those past experiences. Transference has undergone considerable revision in more recent writings, so that today much more emphasis is placed on the clini-cian’s contributions to the patient’s transference. In other words, if a clinician is silent and remote, the patient may experience that clinician as disengaged and cold. While an internal template of past experiences with authority ﬁ  gures may correlate with that percep-

tion, we would also recognize that the clinician’s real behaviour contributes to that precise transference paradigm. In that regard, 
a more contemporary view of transference would be that every treatment relationship is a mixture of new features based on real characteristics of the clinician and old experiences from the patient’s past. Psychodynamic clinicians also recognize a bidimen-sional quality to transference: while one dimension involves repeti-tion of the past, another dimension is seeking an experience with a new object to facilitate further emotional growth.
Central to the psychodynamic viewpoint is that the clinician and the patient bring their own separate subjectivities to an encounter, and mutually inﬂ  uence one another. Countertransference, in this

respect, is the counterpart of transference. In other words, as Freud originally used the term, it referred to the analyst’s attribution of certain qualities to the patient based on the analyst’s past experi-ences with similar ﬁ  gures. This perspective, often referred to as the 
narrow view of countertransference, regarded the phenomenon as an obstacle to be removed because it interfered with the analyst’s objectivity.
Subsequent contributors to the literature on countertransfer-
ence
(6, 7) noted that countertransference with severely disturbed

ence
(6, 7) noted that countertransference with severely disturbed 
patients often involves an objective component. The patient behaves in such a provocative manner that virtually anyone would respond with a certain set of emotional reactions to that patient. This way of looking at countertransference is often regarded as the broad or totalistic view. Inherent in this perspective is that the clinician’s reaction has much less to do with his or her own indi-vidual past than with the speciﬁ  c characteristics of the patient and 
that patient’s capacity to induce strong reactions in others.
As the deﬁ  nition has continued to evolve, countertransference is 
now generally regarded as involving both the narrow and the broad 
characteristics. In other words, most theoretical perspectives view

characteristics. In other words, most theoretical perspectives view 
countertransference as entailing a jointly created reaction in the clinician that stems, in part, from contributions of the clinician’s past and, in part, from feelings induced by the patient’s behaviour.
(8)
In some cases the emphasis may be more on the contributions of the clinician than the patient, while in other cases the reverse may be true. This model also regards countertransference as something of a unique construction that varies depending on the two subjec-tivities involved (see Box 3.3.1). In this contemporary perspective, countertransference is both a source of valuable information about the patient’s internal world and something of an interference with the treatment.

315
In 1912 Freud(9) wrote, ‘The resistance accompanies the treatment

step by step. Every single association, every act of the person under treatment must reckon with the resistance and represents a com-promise between the forces that are striving towards recovery and the opposing ones’ . The patient’s resistance defends the patient’s ill-ness from the clinician’s attempt to treat it and change it. Resistance may be conscious, preconscious, or unconscious. It may take many forms, including not taking medication as prescribed, forgetting appointments with the psychiatrist, changing the subject in the middle of an appointment to something trivial, and discount ing every insight the psychiatrist offers. The patient’s characteristic defence mechanisms are often transformed into resistances in the treatment situation. The dynamic psychiatrist knows that all progress will be accompanied by some degree of resistance, and the explora-tion of resistance is a major part of therapeutic work. Resistance is intimately related to transference because the patient

progress will be accompanied by some degree of resistance, and the explora-tion of resistance is a major part of therapeutic work. Resistance is intimately related to transference because the patient often rebels against the doctor resulting from unconscious transference conﬁ  gu-

rations that lead the patient to oppose the doctor’s help.
The mind–brain interface
The psychodynamic psychiatrist eschews reductionism. Recognizing 
that mental life and psychiatric symptoms are both overdetermined and multiply caused, psychodynamic clinicians are always interest-ed in the interface between the biological and the psychosocial. Psychodynamic psychiatry is not antibiological. The psychody-namic psychiatrist is the integrator par excellence. Avoiding Cartesian dualism, the mind is seen as the expression of the activity of the brain.
(10) Subjective experience affects the brain just as

(10) Subjective experience affects the brain just as 
mental phenomena arise from the brain. Every treatment interven-tion is seen as being biopsychosocial in nature. Medications have psychological effects. Psychotherapeutic interpretations affect the brain. Moreover, psychodynamic psychotherapy and medications may work synergistically to provide better outcomes for patients. For example, a patient with a bipolar disorder who is denying that he has an illness and refusing to take lithium may ultimately have better compliance with the medication if the clinician explores the meaning of his denial and his reluctance to consider himself as someone requiring treatment.
The comprehensive mind–brain strategy of the contemporary 
psychodynamic psychiatrist ﬁ  ts well with our growing knowledge 
of the interaction between genes and the environment. In an inspired series of experiments with the marine snail Aplysia ,
Kandel
(11,12) has demonstrated that synaptic connections are

Kandel
(11,12) has demonstrated that synaptic connections are 
strengthened and permanently altered through regulation of gene expression connected with learning from the environment. In Aplysia  the number of synapses actually double or triple as a result

strengthened and permanently altered through regulation of gene expression connected with learning from the environment. In Aplysia  the number of synapses actually double or triple as a result 
of learning. Kandel has suggested that psychotherapy might make similar neuroanatomical changes in the synapses. He argues that just as representations of self and others are malleable, the brain itself is a dynamic and plastic structure. He postulates that psycho-therapy is a form of learning that produces alteration of gene expression and thereby alters the strength of synaptic connections. While the template function or the sequence of the gene is not affected by environmental experience, the transcriptional function of the gene (namely the ability of a given gene to direct the manu-facture of speciﬁ  c proteins) is highly regulated and responsive to 
environmental factors.
Antisocial personality disorder may be a model disorder with

Antisocial personality disorder may be a model disorder with 
which to examine the interaction of genes and environment. In a perspective study based in Dunedin,
(13) a birth cohort of 1037

(13) a birth cohort of 1037 
children was followed prospectively. By the age of 26, 96 per cent of the sample was contacted and evaluated. Between the ages of 3 and 11 years, 8 per cent experienced ‘severe’ maltreatment, 28 per cent experienced ‘probable’ maltreatment, and 64 per cent experienced no maltreatment. The investigators determined that a functional polymorphism in the gene responsible for the neurotransmitter metabolizing enzyme monoamine oxidase-A (MAO-A) was found to moderate the effect of maltreatment. Males with low MAO-A activity genotype who were maltreated in childhood had elevated antisocial scores. Males with high MAO-A activity did not have elevated antisocial scores, even when they had experienced child-hood maltreatment. Of males with both low MAO-A activity geno-type and severe maltreatment, 85 per cent developed antisocial 
behaviour.
(13)

(13)
The research summarized here points to the dynamic interplay 
between genetic expression and the environment. Gene expression cannot be considered static. It is a dynamic phenomenon that interacts with and reacts to environmental experiences. Heritable characteristics of children actually shape their relationships with their parents and siblings.
(14) In turn, the response of family 
members to the child affect the genetic expression. Hence genetic inﬂ uences on some types of psychopathology may be dependent 
on the mediation of social processes. A child’s genetic endowment will inﬂ  uence the way parents relate to a child, and the way the 
parents treat the child will then inﬂ  uence that child’s developing 
brain. Biological and psychosocial processes are constantly inter-twined, and neither is prior.
In many major psychiatric disorders, such as depression, genetic 
factors appear to inﬂ  uence whether a stressor produces an episode 
of illness.

(15) From a psychodynamic perspective, the meaning of 
stressors must also be incorporated. Some stressors that may seem mild to one individual are overwhelming to another because of their idiosyncratic conscious or unconscious meaning. In addition, the presence of biologically generated symptoms in no way dimin-ishes the importance of meaning. Pre-existing psychodynamic conﬂ  icts may attach themselves to biologically driven symptoms, 
and the symptoms then function as a vehicle for the expression of the conﬂ  icts.
(16) Auditory hallucinations are generated by altera-
tions in neurotransmitters in persons with schizophrenia, but Box 3.3.1 Changing views of countertransference
Narrow  The original Freudian view connoting the analyst’s

Narrow  The original Freudian view connoting the analyst’s 
transference to the patient: an obstacle to be removed through careful analysis of the clinician.Broad or totalistic  All the feelings experienced towards the 
patient, some of which are induced by the patient’s behaviour.Joint creation  The contemporary perspective that emphasizes 
mutual contributions from the patient’s behaviour toward the clinician and the clinician’s past experiences with similar ﬁ  gures. 
This perspective emphasizes countertransference as a source of valuable information in addition to being an interference.3.3 current psychodynamic approaches to psychiatry

SECTION 3  psychodynamic contributions to psychiatry 316
the content of the hallucination often has speciﬁ  c meanings based 
on the patient’s psychodynamic conﬂ  icts. Hence a patient who is 
being told that he is a failure and should kill himself by a halluci-nated voice may be tormented by a sense that his life is shattered by his illness and that he no longer has any purpose in living.
Development of personality
Another key component of the psychodynamic approach is that the clinician treats the person and not just the illness. In practice, that perspective means taking the personality into account in every case. The interface of the biological and the psychosocial is particu-larly apparent in the area of personality. The psychobiological model of personality developed by Cloninger et al.
(17) recognizes

(17) recognizes 
an equal contribution of biological and environmental factors (see Table 3.3.2). The four dimensions of temperament are roughly 50 to 60 per cent heritable independently of one another. They all manifest themselves early in life, and they involve preconceptual biases, habit formation, and perceptual memory. They include the following:
1 novelty-seeking: characterized by active avoidance of frustration, 
quick loss of temper, impulsive decision-making, frequent exploratory activity in response to novelty, and extravagance in the approach to cues and rewards
2 harm-avoidance: which involves pessimistic worry about the 
future, passive avoidant behaviour such as fear of uncertainty, shyness regarding strangers, and rapid fatiguability
3 reward-dependence: characterized by sentimentality, social 
attachment, and dependence on the approval of others
4 persistence: which refers to the capacity to persevere despite 
fatigue and frustration

Certain of these temperament dimensions appear to correlate 
with speciﬁ  c types of personality disorders. The cluster A person-
alities in DSM-IV , for example, are strongly associated with low reward-dependence. Cluster B personality disorders have been shown to be high in novelty-seeking, while cluster C personality disorder patients tend to rate high in harm-avoidance.
The other component of personality in this model is character. 
While temperament is genetically based, character is shaped by environmental experiences, such as family relationships, peer relationships, trauma, and neglect. These dimensions appear to make up about 50 per cent of personality. There have been three dimensions of character identiﬁ  ed that appear to mature in adult-
hood. These dimensions inﬂ  uence social and personal effectiveness

hood. These dimensions inﬂ  uence social and personal effectiveness 
by insight-learning about self-concepts. The three character dimen-sions are self-directedness, cooperativeness, and self-transcendence.
Low self-directedness and low cooperativeness are associated 
with all categories of personality disorder in the DSM-IV sys-tem.
(17) Self-transcendence, on the other hand, does not differentiate 
patients with personality disorders from those without personality disorders.
Self-directedness and cooperativeness reﬂ  ect two fundamental 
tasks in personality development as deﬁ  ned by Blatt et al.
(18): the

(18): the 
achievement of a stable, differential, realistic, and positive identity, and the establishment of enduring, mutually gratifying relation-ships with others. These two dimensions evolve in a dialectical and synergistic relationship to one another throughout the life cycle. Patients with character pathology tend to divide into two groups: introjective types, who are primarily focused on self-deﬁ  nition; 
and anaclitic types, who are more concerned about relatedness.
The character dimensions readily lend themselves to typical psy-

chodynamic constructs. The self-directedness dimension is closely linked to what are often called ego functions or self-structures. The dimension of cooperativeness is a direct measure of a person’s characteristic pattern of internal object relations as they are exter-nalized in relationships with others. In one’s assessment of a 
patient’s personality, the transference–countertransference dimen-
sions of the clinical interaction provide a privileged glimpse of the typical patterns of relatedness that cause difﬁ  culties in the patient’s 
outside relationships.
(19) The patient is involved in an ongoing 
attempt to actualize certain patterns of relatedness that reﬂ  ect vari-
ous wishes in the patient’s unconscious. Through the patient’s behaviour, he or she subtly tries to impose on the clinician a certain way of responding and experiencing.
(20)

(20)
An individual internalizes a self-representation in interaction 
with an object representation connected by an affect through a series of repetitive interactions in childhood. This pattern ulti-mately leads to an internalized set of self- and object representa-tions in interaction with one another. The adult individual repeats these patterns again and again as an effort to fulﬁ  ll an unconscious 
wish. Even abusive or painful relationships involving a ‘bad’ or tor-menting object may be wished for because of the safety and afﬁ  r-
mation such relationships provide. In other words, a child who has been abused has internalized a highly conﬂ  ictual abusive relation-

ship as a predictable and familiar pattern. Having an abusive object may be preferable to having no object at all or being abandoned. Many patients with histories of an abusive childhood become con-vinced that the only way to remain connected to a signiﬁ  cant per-
son is to maintain an abuser–victim relationship.
The repetitive interactions seen in patients with personality dis-
order may reﬂ  ect actual relationships with real objects in the past, 
but they may also involve wished-for relationships, such as those often seen in patients with childhood trauma who seek a rescuer. Clinicians who are inﬂ  uenced by the patient’s interpersonal pres-
sure to respond in a particular way may unconsciously accept the role in which they have been cast. When this phenomenon occurs, it is often referred to as projective identiﬁ  cation.
(8) In other words,

(8) In other words, 
the patient may ‘nudge’ the therapist into assuming the role of an abuser in response to the patient’s ‘victim’ role, and the therapist may feel countertransference hate or anger and begin to make sar-castic or demeaning comments to the patient.Table 3.3.2  Development of personality
 Personality  
Temperament
(50% contribution)Character
(50% contribution)
Novelty-seeking Self-directedness
Harm-avoidance Co-operativeness
Reward-dependence Self-transcendence
Persistence
Reproduced from Cloniger, C.R., Svarik, D.M. and Pryzbeck, T.R. (1993). A Psychobiological 
model of temperament and character. Archives of General Psychiatry , 50, 975−90. 
Copyright 2003, The American Medical Association.

317
In addition to this pattern of object relations, the other major 
component of character, from a psychodynamic perspective, is the particular constellation of defence mechanisms that characterizes the individual patient.
(21) While defences were traditionally regard-
ed as intrapsychic mechanisms designed to prevent awareness of unconscious aggressive or sexual wishes, the current understand-ing of defence mechanisms has been expanded far beyond Freud’s dual-drive theory. We now understand that defences also preserve a sense of self-esteem in the face of narcissistic vulnerability, assure safety when one feels dangerously threatened by abandonment, and serve to insulate one from external dangers through, for exam-ple, denial or minimization.
Different personality types or disorders use characteristic sets of

Different personality types or disorders use characteristic sets of 
defence mechanisms. For example, the paranoid personality may typically use projection as a way of disavowing unacknowledged feelings and attributing them to others. Patients with obsessive–compulsive personality disorder may use defensive operations such as isolation of affect, intellectualization, and reaction formation to control affective states that are highly threatening. In the relation-ship with the clinician, as noted previously, these defences will manifest themselves as resistances. Hence, if a patient with an obsessive–compulsive personality disorder uses intellectualization as a defence against painful affects, when the patient comes to treat-ment, intellectualization will be used as a resistance to avoid getting at feelings in psychotherapy.
Dynamic pharmacotherapy

The commonly used psychodynamic constructs, such as therapeu-tic alliance, transference, countertransference, and resistance apply to all modalities of psychiatric treatment, even though their usage is generally associated with psychodynamic psychotherapy. In a study of the relationship between the therapeutic alliance and the outcome of 250 depressed outpatients in the National Institute of Mental Health Treatment of Depression Study,
(22) the therapeutic

(22) the therapeutic 
alliance was found to be of extraordinary importance. The patients had been randomly assigned to one of four conditions: brief inter-personal therapy, brief cognitive behavioural therapy, imipramine plus clinical management, or placebo plus clinical management. The researchers found that the therapeutic alliance was just as important for drug therapy as for psychotherapy. In all four treat-ment cells, the therapeutic alliance counted for more of the vari-ance of treatment outcome than the treatment method itself. This was the ﬁ  rst empirical study to show the importance of the thera-
peutic alliance in psychotherapy, pharmacotherapy, and placebo outcome.
Non-compliance is one of the most challenging problems facing 
psychiatric practitioners. Many factors go into compliance. 
Although many patients blame side effects, they often uncon-

sciously undermine the treatment plan. The patient may have a negative transference to the prescribing clinician related to atti-tudes toward parents and other authority ﬁ  gures that lead the 
patient to rebel and defy the doctor’s orders. Some clinicians may have countertransference reactions to speciﬁ  c patients that lead 
them to prescribe in a highly authoritarian manner or a tentative and ambivalent manner, giving unconscious messages to the patient that reﬂ  ect the doctor’s attitude about the medication. Patients 
who feel the doctor is bullying them to take the medication may not comply. Similarly, patients who sense their doctor is ambivalent about the value of the medication may also choose not to 
ﬁ ll the prescription. Unconscious resistance is frequently a major

ﬁ ll the prescription. Unconscious resistance is frequently a major 
factor in non-compliance. Medications may have idiosyncratic meanings to patients based on unconscious identiﬁ  cations with 
family members who have taken the same medication, views of psychiatric illness as moral weakness, or fears about the effects of the medication. Sometimes a pill or capsule may serve as a transi-tional object that substitutes for the person of the prescriber when the physician is unavailable. The colour or shape of a tablet may take on special signiﬁ  cance for some patients, making them reluc-
tant to change dosage or switch to another medication.
Multiple-treater settings
In inpatient units and partial hospital settings, psychodynamic concepts are of considerable value in understanding the patient’s psychopathology as it unfolds in a group setting. Patients re-create their internal object relations in the inpatient or partial hospital milieu.

(23) The conﬂ  icts that occur in their family context will re-
emerge in their relationships with hospital staff members. Through projective identiﬁ  cation the patient subtly pressures various staff 
members to play the roles that are in keeping with the patient’s internal world. Hence a patient who has been physically and/or sexually abused by a parent will behave in such a way toward a cer-tain nurse, for example, that the nurse begins to feel abusive toward the patient. The same patient may treat another nurse as an ideal-ized rescuer ﬁ  gure, eliciting loving and protective feelings from that 
nurse. This form of splitting
(23) may create extraordinary conﬂ  icts 
between staff members over the best treatment approach to the patient. Therefore failure to attend to the transference–counter-transference dimensions of the milieu treatment may lead to a total disruption of the staff members’ capacity to be effective with cer-tain patients.

Moreover, individual patients often act out covert staff conﬂ  icts. 
Psychodynamically informed hospital treatment may help to iden-tify these conﬂ  icts and allow staff to process them in such a way 
that the patients no longer need to enact them. When covert con-ﬂ icts between staff members become overt and open to discussion, 
the patient’s disruptive behaviour often settles down.
(23) This 
observation reﬂ  ects how the dynamics of the patient group and 
staff group often parallel each other. The psychodynamic clinician also understands that individuals behave differently in groups than they do alone or in a one-to-one context. Powerful group forces, such as scapegoating, can be recognized and processed so they do not become destructive to treatment. Similarly, the patient’s recur-rent problems in groups can be diagnosed, in part, by a careful study of the transference and countertransference responses.
Two-person context of treatment

One of the major shifts in psychodynamic thinking in recent years has been a greater acknowledgement of the inﬂ  uence of the clini-
cian’s perspective on the observations about the patient. Postmodern contributions from intersubjectivity and social constructivism have challenged the view that the clinician assesses the patient from a detached and objective frame of reference. Fundamental to this perspective is that clinicians can never transcend their irreducible subjectivity.
(24) The psychiatrist in this context can never fully 
know how his or her subjectivity is inﬂ  uencing the diagnostic 3.3 current psychodynamic approaches to psychiatry

SECTION 3  psychodynamic contributions to psychiatry 318
assessment or the treatment process. Countertransference is viewed 
as both unconscious and continuous, so that a therapist cannot possibly be capable of keeping up with every emotional reaction of the patient.
(25)
This two-person model of the treatment situation has contrib-
uted to the demise of the classical psychoanalytical view of the therapist or analyst as a blank screen or a dispassionate observer. The inﬂ  uence of the clinician’s biases and unconscious feelings 
toward the patient may have far-reaching implications for a variety of situations in psychiatry. Frustration about a patient’s non-responsiveness to treatment, for example, can lead a clinician to recommend electroconvulsive therapy as a reaction to despair, rather than as a result of systematic decision trees or algorithms about refractory depression. Even in the case of physician-assisted suicide, countertransference may play a major, though hidden, role.

(26) Within this context the patient’s wish to die may stem from 
a self-concept as worthless and a burden to others that is, in part, a reﬂ ection of what the physician brings to the encounter. Similarly, 
the doctor’s death-anxiety might underlie an omnipotent need to triumph over death through the prescription of physician-assisted suicide that strives to preserve an illusion of control and mastery. In the worst scenario, a clinician’s intense countertransference hate toward a patient may lead to a wish to kill that is transposed into a recommendation for physician-assisted suicide.
Psychodynamic psychotherapy for 
speciﬁ  c disorders
A psychodynamic approach is relevant to the treatment of the vast

A psychodynamic approach is relevant to the treatment of the vast 
majority of psychiatric disorders encountered in clinical practice. Depending on the nature of the illness, the setting in which the ill-ness is treated, and the psychological mindedness of the patient, psychodynamic strategies may be the major emphasis in the treat-ment plan or a relatively minor contribution. Psychodynamicpsychotherapy per se is generally divided into short-term psy-chodynamic psychotherapy (STPP) and long-term psychodynamic psychotherapy (LTPP). The former is generally regarded as involv-ing fewer than 24 sessions or 6 months’ duration, while the latter is viewed as a therapy lasting more than 6 months.
(27) Psychodynamic 
psychotherapy, whether long-term or short-term, is often deﬁ  ned

psychotherapy, whether long-term or short-term, is often deﬁ  ned 
as ‘a therapy that involves careful attention to the therapist–patient interaction, with thoughtfully timed interpretation of transference and resistance embedded in the sophisticated appreciation of the therapist’s contribution to the two-person ﬁ  eld’ .
(28) This form of 
psychotherapy is also conceptualized as operating on an expressive-supportive continuum. The highly expressive forms of psychodynamic psychotherapy offer more interpretation of unconscious conﬂ  ict, while the forms that are more supportive 
focus on bolstering adaptive defences and building self-esteem. The continuum of interventions from the most expressive to the most 
supportive (see Table 3.3.3) guide the psychotherapist in how to intervene with any given patient.
Short-term psychodynamic psychotherapy
A recent meta-analysis of STPP(29) found that this modality made

A recent meta-analysis of STPP(29) found that this modality made 
signiﬁ  cant changes in general psychiatric symptoms, target prob-
lem, and social functioning. The treatment also yielded signiﬁ  cant 
and large pre-treatment—post-treatment effect sizes. The effect sizes were stable and tended to increase at follow-up. No signiﬁ  cant 
differences were found between STPP and other forms of psycho-therapy. Evidence from randomized controlled trials supports the use of STPP for major depressive disorder, panic disorder, social phobia, and post-traumatic stress disorder. In addition, the treat-ment has also been efﬁ  cacious in somatoform disorders, bulimia 
nervosa, and substance-related disorders in association with drug counseling.
Long-term psychodynamic psychotherapy

Research on LTPP has been more limited than for STPP because the gold standard of the randomized controlled trial is more difﬁ cult to implement when studying LTPP . One must ﬁ  nd a suit-
able control group where an alternative extended treatment or a placebo condition can be implemented. The most rigorous controlled condition is an alternative extended treatment, although some investigations have used treatment as usual as well.
(30) The 
dropout rate can also be problematic in long-term studies. In addi-tion, intervening life events, Axis I conditions, and medication shifts can inﬂ  uence outcome. Nevertheless, despite the obstacles 
to designing and implementing rigorous research on LTPP , there are a number of studies that have appeared in recent years that suggest that LTPP is an efﬁ  cacious treatment.

Two randomized controlled trials have shown LTPP to be efﬁ  ca-
cious with Cluster C personality disorders. Included in this group are avoidant, dependent, and obsessive–compulsive personality disorders. One study compared 40 sessions of psychodynamic ther-apy to control patients on a waiting list and found substantially better outcomes than those who received the dynamic therapy.
(31)
In a more rigorously designed study,(32) 40 sessions of dynamic 
psychotherapy were compared to 40 sessions of cogniti ve behaviour 
therapy. While both treatments were effective, the dynamic therapy resulted in continued improvement after termination of treatment, suggesting that patients internalized the therapeutic dialogue and used it to deal with problems as they arose.

Borderline personality disorder has also been subjected to rigorous
trials of long-term psychodynamic psychotherapy. In one head-to-head comparison between a form of LTPP known as transference-
focused psychotherapy (TFP), dialectical behaviour therapy (DBT), 
and supportive psychotherapy (SPT),
(33, 34)  all three modalities 
Table 3.3.3 An expressive–supportive continuum of interventions
                        E n c o u r a g e m e n t       A d v i c e
  I n t e r p r e t a t i o n    C o n f r o n t a t i o n           t o     E m p a t h i c    a n d
        O b s e r v a t i o n      C l a r i ﬁ  c a t i o n   E l a b o r a t e    V a l i d a t i o n   P r a i s e
E x p r e s s i v e                                     S u p p o r t i v e
(Data modiﬁ  ed from Gabbard, G.O. (2004), Long-term psychodynamic psychotherapy: a basic text , American Psychiatric Publishing, Arlington, VA.)

319
showed general improvement. However, TFP showed improve-
ments that were not demonstrated by either SPT or DBT. Participants in the study who received TFP were more likely to move from an insecure attachment classiﬁ  cation to a secure one, 
show greater changes in mentalizing capacity, and have more extensive symptomatic improvement than the other two groups. Only TFP made signiﬁ  cant changes in impulsivity, irritability, ver-
bal assault, and direct assault. Suicidality was reduced to an equal extent by TFP and DBT.
A psychoanalytically oriented partial hospitalization treatment 
for patients with borderline personality disorder was compared to a treatment-as-usual approach.
(35,36)  In the treatment group, the 
major difference was the provision of individual and group psy-chotherapy compared to the control condition. The treatment lasted a maximum of 18 months, and was signiﬁ  cantly superior

major difference was the provision of individual and group psy-chotherapy compared to the control condition. The treatment lasted a maximum of 18 months, and was signiﬁ  cantly superior 
to standard psychiatric care, both at the end of therapy and at the 18-month follow-up.
A randomized controlled trial for children with learning dis-
abilities
(37) compared intensive psychodynamic therapy (four times 
a week) to once-a-week sessions. This trial on featured treatments had lasted longer than 1 year. In the follow-up assessment, chil-dren who had sessions four times a week showed much greater improvement.

The psychodynamic model continues to enrich the patient’s understanding and the psychiatrist’s practice. The time-honoured principles elaborated here serve as windows into the murky recesses of the unconscious and illuminate human motivation. They also provide the clinician with a ‘second sight’ that helps make sense out of bewildering and complex clinical situations.The evidence regarding the impact of psychotherapy on the brain opens up new lines of investigation to enhance our understanding of psychopathology and treatment. These include the following:
1 the mechanisms of action of psychotherapy2 the interrelationships between the mechanisms of action of psy-
chotherapy and medication
3 a clearer understanding of pathogenesis itself and the malleabil-
ity of some components of the pathogenetic mechanisms of major psychiatric disorder
Research is sorely needed on psychodynamic treatments because

Research is sorely needed on psychodynamic treatments because 
there is only a modest empirical base for psychodynamic therapy. Many more studies are needed, especially those with a randomized controlled design targeted at speciﬁ  c disorders. Studies investigat-
ing extended dynamic therapy of a year or more are needed to demonstrate which patients beneﬁ  t from the additional investment 
of time and money. In the current climate of cost containment, practitioners of psychodynamic therap y must take c ost-effectiveness 
into account.
The optimal treatment for many psychiatric patients involves a

The optimal treatment for many psychiatric patients involves a 
combination of medication and psychotherapy, but research support for this view is also rather modest. Controlled studies of combined treatment versus single modalities are needed for personality disor-ders and anxiety disorders. In addition, the role of psychodynamic thinking in compliance problems needs rigorous investigation.
In the meantime, the psychodynamic model continues to focus 
on the uniqueness of the individual patient. Psychodynamic psychiatry, above all, is interested in the person with illness rather 
than the illness alone.
Gabbard, G.O. (2004). Long-term psychodynamic psychotherapy: a basic text .
American Psychiatric Publishing, Arlington, V A.
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4.1 Delirium, dementia, amnesia, and 
Mario Maj

Jonathan J. Evans 4.2 Substance use disorders  426
 4.2.1 Pharmacological and psychological aspects of drugs abuse  
426
Robin Room

Robin Room
and other ‘party drugs’   494
Wayne HallSECTION 4
Clinical Syndromes 

322
Anthony S. David
 4.3.5 Epidemiology of schizophrenia  540
578

578
Per Bech
637
Peter R. Joyce 4.5.5 Genetic aetiology of mood disorders  650

Anke Ehlers, Allison G. Harvey, and Richard A. Bryant
Anke Ehlers
  4.7.1 Generalized anxiety disorders  729
  4.7.2 Social anxiety disorder and speciﬁ  c
phobias  739
Michelle A. Blackmore, Brigette A. Erwin,

4.7.1 Generalized anxiety disorders  729
  4.7.3 Panic disorder and agoraphobia  750

4.11.2 The sexual dysfunctions  821
855
James Reich and Giovanni de Girolamo
 4.12.3 Speciﬁ  c types of personality disorder  861
886

4.12.7 Management of personality disorder  901
Susan L. McElroy and Paul E. Keck Jr. 4.13.2 Special psychiatric problems relating to gambling  
919
957
969

969

Delirium, dementia, amnesia, 
and other cognitive disorders4.1
4.1.1 Delirium
Delirium is an acute or subacute, usually reversible syndrome of 
impaired higher cortical functions hallmarked by generalized cog-nitive disturbance and caused by one or more aetiologies. It is most common in medical-surgical patients, especially in intensive care units, and those in hospice and nursing homes. The term ‘delirium’ derives from the Latin ‘ lira’ meaning literally to wander from the 
furrow. Prior to DSM-III (1980) such disturbances were described by a plethora of labels (acute organic brain syndrome, acute confu-sional state, brain failure, toxic encephalopathy, intensive care psychosis), before Lipowski advocated for the umbrella term delir-ium to subsume these multiple synonyms. This engendered a more scientiﬁ  c research effort and consistent approach to detection and

management. Though delirium has been recognized for at least two millenia, it is only now beginning to receive the attention that 
it warrants, with increasing appreciation of the considerable impact 
upon outcomes and independent need for treatment as a brain dis-order beyond only treating its underlying aetiological precipitants.
Inattention is the cardinal disturbance, including distractibility, 
reduced vigilance or concentration, and impaired environmental awareness. This contrasts with dementia, another disorder of generalized cognitive deﬁ  cits, where memory deﬁ  cits are cardinal.

reduced vigilance or concentration, and impaired environmental awareness. This contrasts with dementia, another disorder of generalized cognitive deﬁ  cits, where memory deﬁ  cits are cardinal. 
While full-blown episodes are easier to diagnose, its prodrome, subclinical presentation, and potential persistence present unre-solved dilemmas regarding diagnostic boundaries of delirium. Further, comorbidity with dementia presents challenges for detec-tion and attribution of progressive impairments in the elderly. Though delirium occurs at any age, there is a dearth of research in younger age groups such that it is unclear whether research ﬁ  nd-
ings from geriatric studies can be generalized to other age groups (e.g. regarding risk factors and outcomes). Studies that clarify com-mon features such as phenomenology, neural circuitry or electro-
physiology are thus critical.Contents
 4.1.1 Delirium
 4.1.2 Dementia: Alzheimer’s disease

 4.1.3 Frontotemporal dementias
 4.1.4 Prion disease
 4.1.5 Dementia with Lewy bodies
 4.1.6 Dementia in Parkinson’s disease
 4.1.7 Dementia due to Huntington’s disease
 4.1.8 Vascular dementia
 4.1.9 Dementia due to HIV disease
Mario Maj
 4.1.10 The neuropsychiatry of head injury
dementia; alcohol-related brain damage)
 4.1.12 Amnesic syndromes
 4.1.13 The management of dementia
 4.1.14 Remediation of memory disorders
Jonathan J. Evans

SECTION 4  clinical syndromes of adult psychiatry 326
Clinical features
Delirium is a complex neuropsychiatric syndrome with a broad 
range of cognitive and neurobehavioural symptoms which is why it can be misattributed to other psychiatric disorders by nonspecial-ists. Symptoms involve cognition, thought, language, sleep-wake cycle, perception, affect, and motor behaviour. The constellation of symptoms—along with the cardinal symptom of inattention and acute onset and ﬂ  uctuating temporal course—are characteristic of 
delirium and when comorbid with dementia, delirium dominates the clinical presentation.
(1) Phenomenology studies (mostly cross-
sectional) suggest that ‘core’ symptoms occur with greater frequency while other less consistent ‘associated’ symptoms may reﬂ  ect the 
biochemical inﬂ  uence of particular aetiologies or genetic, neuronal

biochemical inﬂ  uence of particular aetiologies or genetic, neuronal 
or physiological vulnerabilities (see Table 4.1.1.1). Accumulating evidence indicates three core domains of delirium phenomenology: ‘Cognition’ comprising of inattention and other cognitive deﬁ  cits; ‘Higher Level Thinking Processes’ including impaired executive 
function, semantic expression, and comprehension; and ‘Circadian Rhythm’ including fragmented sleep-wake cycle.
(2) The underlying 
neural support for these domains is consistent with neuroanatomi cal 
findings in lesion and functional neuroimaging studies that implicate certain brain regions and neural circuitry.
Delirium occurs as a stage of consciousness in the continuum

Delirium occurs as a stage of consciousness in the continuum 
between normal awakeness/alertness and stupor or coma. During the 20th century, delirium was described as a ‘clouding of conscious-ness’ but this rather nebulous concept has been replaced by a better understanding of the components of phenomenology that culminate in severely impaired higher order brain functions. Speciﬁ  cally, a disproportionate disturbance of attentional processes, 
including environmental awareness difﬁ  culties, along with impaired 
higher level thinking reﬂ  ected in irrelevant, unfocused or illogical 
thought processes and impaired abstraction and comprehension
(i.e. executive cognition and semantic language function) typiﬁ  es the 
delirious state. Sleep-wake cycle fragmentation belies a circadian dis-turbance that may contribute to the abnormal level  of consciousness

delirious state. Sleep-wake cycle fragmentation belies a circadian dis-turbance that may contribute to the abnormal level  of consciousness 
and alterations in motor behaviour, where hypoactivity contributes to difﬁ  culties in differential diagnosis of delirium from stupor. 
Delirium is distinguished from stuporose states by the presence of arousability. The majority of intensive care unit patients emerging from comatose states experience a period of diagnosable delirium.
(3)
Inattention  is the cardinal and required symptom to diagnose 
delirium and is noticeable on interview by distractibility, spatial inattention, and inability to sustain attention. More formal testing can be assessed using months of the year backwards or digit span. The Cognitive T est for Delirium (CTD)
(4) allows for separate visual

(4) allows for separate visual 
digit span and vigilance testing. Memory impairment—of both short and long term—can be affected by inattention but appears to be independently impaired. Visuospatial impairment can be assessed by observing patient behaviour in their immediate environment e.g. losing their way or getting lost. Constructional ability can be tested formally by copying ﬁ  gures; clock face drawing 
assesses not only proportions and de tails but also involves prefrontal 
executive functions for placing the minute hand correctly. Delirious patients have executive dysfunction affecting abstraction, initiation/perseveration, switching mental sets, working memory, temporal sequencing and organization, insight and judgment. Poor perfor-mance on the Trailmaking Part B test distinguishes delirious from nondelirious patients and requires not only spatial attention and

concentration but also switching mental sets. Though none of these cognitive deﬁ  cits is speciﬁ  c to delirium, the array and pattern is 
highly suggestive.
Thought process abnormalities  in delirium range from circum-
stantiality and tangentiality to frank loose associations in more severe cases. Naming impairment is common though more severe cases can mimic ﬂ  uent dysphasia with semantic deﬁ  cits being 
characteristic such that communication is wrought with deﬁ  cits 
of meaningfulness. Interestingly, the dysphasia can be mistaken for Wernicke’s aphasia and possible stroke but is reversible when the delirium clears. Careful assessment can usually distinguish between semantic deﬁ  cits (language impairment) and loose associations 
(thought process disorder) except with word salad.
Disruption of sleep-wake cycle  is essentially ubiquitous in delirium

Disruption of sleep-wake cycle  is essentially ubiquitous in delirium 
except in the briefest episodes (e.g. concussion) and often predates the appearance of a full-blown episode. Minor disturbances with insomnia or excessive daytime somnolence may be hard toTable 4.1.1.1  Symptoms of delirium
Diffuse cognitive deﬁ  cits
 Attention
 Orientation (time, place, person) Memory (short- and long-term; verbal and visual) Visuoconstructional ability Executive functions
Temporal course
 Acute/abrupt onset Fluctuating severity of symptoms over 24-hr period Usually reversible Subclinical syndrome may precede and/or follow the episode
Psychosis
  Perceptual disturbances (especially visual), including illusions, hallucinations, 
metamorphosias
 Delusions (usually paranoid and poorly formed) Thought disorder (tangentiality, circumstantiality, loose associations)
Sleep-wake disturbance

 Fragmented throughout 24-hr period Reversal of normal cycle Sleeplessness
Psychomotor behavior
 Hyperactive Hypoactive Mixed
Language impairment
 Word-ﬁ  nding difﬁ  culty/dysnomia/paraphasia Dysgraphia Altered semantic content Severe forms can mimic expressive or receptive aphasia
Altered or labile affect
 Any mood can occur, usually incongruent to context Anger or increased irritability common Hypoactive delirium often mislabeled as depression Lability (rapid shifts) common Unrelated to mood preceding delirium
(Reproduced from Trzepacz, P . T., Meagher, D.J. Delirium, Chapter 11 in American Psychiatric 
Publishing Textbook of Neuropsychiatry , (5th edn) eds. S. Yudofsky and R. Hales, copyright 
2007, American Psychiatric Publishing, Inc., Washington DC.)

327
distinguish from other medically ill patients without delirium, but 
more substantial alterations involve sleep fragmentation or even complete sleep-wake cycle reversal that reﬂ  ect disturbed circadian 
rhythm regulation. The relationship of circadian disturbances to the characteristic ﬂ  uctuating severity of delirium symptoms over 
a 24 hr period or to motor disturbance is unknown.
Motor activity alterations  are very common in delirium. They 
have been used to deﬁ  ne clinical subtypes (hypoactive, hyperactive, 
mixed) though studies are inconsistent as to the prevalence of these subtypes and often include nonmotor symptoms in descriptions. Cognitive impairments and EEG slowing are comparable in hyper-active and hypoactive patients though other symptoms may vary. Psychotic symptoms occur in both although the prevailing stereo-type suggests that they only occur in hyperactive cases. Hypoactive 
cases are prone to non detection or misdiagnosis as depression.

cases are prone to non detection or misdiagnosis as depression. 
A range of studies suggest that motor subtypes differ regarding underlying pathophysiology, treatment needs, and prognosis for function and mortality though inconsistent subtype deﬁ  nitions 
and delayed/poorer detection of hypoactives impacts interpreta-tion of these ﬁ  ndings.
Psychotic symptoms  occur in up to 50 per cent of patients with 
delirium. Thought content abnormalities include suspiciousness, overvalued ideation and frank delusions. Delusions are typically poorly-formed and less stereotyped than in schizophrenia or Alzheimer’s disease. They usually relate to persecutory themes of impending danger or threat in the immediate environment (e.g. being poisoned by nurses), and less commonly to grandiose themes. Misperceptions include depersonalization, delusional misidentiﬁ  -

cations, illusions and hallucinations. Hallucinations and illusions are primarily visual though they can be tactile and auditory where-as auditory modalities tend to dominate in psychosis in mood and primary psychotic disorders. Formications suggest dopamine or anticholinergic toxicity.
Delirium may be abrupt as with concussion, drug intoxication or 
stroke, or can be preceded by a prodromal period characterized by anxiety, sleep disturbance, cognitive impairments and increased lev-els of perceived distress. Symptom proﬁ  le appears similar across age 
groups
(5) but delirium is understudied in pediatric patients. The 
propensity for particular aetiologies to shape clinical presentation is also understudied. Unfortunately, delirium tremens (with ﬂ  orid

propensity for particular aetiologies to shape clinical presentation is also understudied. Unfortunately, delirium tremens (with ﬂ  orid 
psychosis and agitation) is the dominant clinical stereotype even though many cases present with relative hypoactivity especially in the elderly, those with concomitant dementia, or where delirium is related to metabolic causes or organ failure. This misleading stereo-type is one of the reasons for the poor recognition of delirium where typically 50 per cent of cases are missed in routine clinical practice.
Diagnosis and differential diagnosis
ICD-10 and DSM-IV share key features used to diagnose delirium (i.e. acute onset, ﬂ  uctuating course, inattention, and disorganized

ICD-10 and DSM-IV share key features used to diagnose delirium (i.e. acute onset, ﬂ  uctuating course, inattention, and disorganized 
thinking) although the ICD-10 description gives better account of the breadth of symptoms that can occur (e.g. disturbances of sleep and motor activity). DSM IV is more inclusive and preferred in research studies, though may be less rigorous than ICD-10 when used by less skilled clinicians. DSM-IV classiﬁ  es cases according to presumed aeti-
ological cause, though a single aetiology occurs in less than half of cases and no aetiology is identiﬁ  ed in around 10 per cent. Delirium is 
also subclassiﬁ  ed according to its relatio nship to dementia.Delirium is poorly detected in clinical practice by nonpsychia-
trists with more than 50 per cent of cases missed, misdiagnosed, or diagnosed late. This is due to multiple factors: the complex and ﬂ  uctuating nature of delirium symptoms, inadequate educa-

tion and interview skills of nonpsychiatrists, underappreciation of the prognostic signiﬁ  cance of delirium, and inadequate routine 
cognitive screening in real world practice. Delirium can be the ﬁ rst indicator of serious physical morbidity (e.g. stroke) and repre-
sents a medical emergency. It is not surprising therefore that non-detection is associated with poorer outcomes that include elevated mortality.
(6) Poor outcomes in hypoactive patients may be in part 
due to nondetection.
The course of delirium is highly variable reﬂ  ecting the heteroge-

neity of aetiology and patient populations in which deliriumoccurs, with recent studies emphasizing that it is frequently notthe benign and transient condition that was previously thought. While in many cases, delirium is brief (hours to days), representsa transitional state from unconsciousness or is a benign reactionto treatment exposures, in other cases it can be more prolonged (e.g. after traumatic brain injury) or associated with seriouscomplications and persistent cognitive difﬁ  culties where differen-
tiation from dementia becomes difﬁ  cult. Rudberg et al.
(7) studied 
elderly medical-surg ical inpatients with delirium and found that 
episode duration was 24 hrs or less in over two-thirds of patients. Conversely, Sylvestre et al .
(8) studied elderly medical admissions

(8) studied elderly medical admissions 
over two-month follow-up and identiﬁ  ed ﬁ  ve separate patterns of 
recovery, with fast improvement in only 11 per cent of patients. Greater clarity regarding the factors that shape these varying courses is needed.
Delirium diagnosis is complicated by comorbidity  where over 
50 per cent of cases are superimposed on dementia or other pre-existing cognitive impairments. Distinguishing delirium from the neuropsychiatric symptoms of dementia can be challenging but acute onset, ﬂ  uctuating course, temporal relationship to an identi-
ﬁ able physical precipitant, prominent inattention and altered level 
of consciousness usually allow differentiation. Third party infor-mants and previous medical charts can be crucial in clarifying the trajectory of cognitive impairment. Studies comparing symptoms

of consciousness usually allow differentiation. Third party infor-mants and previous medical charts can be crucial in clarifying the trajectory of cognitive impairment. Studies comparing symptoms 
of delirium and dementia indicate that where they coexist, deliri-
um symptoms dominate the clinical picture. Given the poor prog-nostic implications of delirium, a management hierarchy applies with delirium taking diagnostic precedence over other neuropsy-chiatric disorders so that any acute alteration in mental state is pre-sumed to be delirium until otherwise established.
Some symptoms of delirium also overlap with primary psychiatric 
disorders . Major depressive disorder can be misdiagnosed

disorders . Major depressive disorder can be misdiagnosed 
in hypoactive presentations or when affective lability includes tearfulness and sad mood. Agitated depression or severe mania (‘Bell’s mania’) can mimic hyperactive delirium but the affective lability and incongruent moods of delirium contrast with more sustained alterations in mood and effect in major mood disorders. The character of psychotic symptoms in delirium differs from primary psychotic illness (see above). Ac ute schizophr enic psy chosis 
involves disorganized thoughts with delusions and hallucinations but inattention is less prominent. Acute schizophrenia can include marked cognitive impairment with perplexity that can mask or be mistaken for comorbid delirium and in such cases the EEG can be helpful. Table 4.1.1.2 describes key clinical features for differentiat-ing delirium from other neuropsychiatric conditions.4.1.1 delirium

SECTION 4  clinical syndromes of adult psychiatry 328
Nondetection of delirium  is particularly common in older patients 
with comorbid dementia, multiple medical problems and hypoactive motor presentations. Chronic subsyndromal delirium in the elderly is commonly related to low grade infections or medication adverse effects, where adjusting medications can signiﬁ  cantly improve cog-
nition. Monitoring for any acute deterioration from baseline func-tion coupled with regular formal assessment with simple cognitive tests such as the digit span, months of year backwards, serial sevens or clock drawing enables delirium detection. Unfortunately, over-reliance on orientation as a measure of cognition precludes more accurate detection. The emphasis on orientation, inconsistent administration, and ceiling effects limit the usefulness of the (MMSE) in measuring delirium. The Cognitive T est for Delirium was designed speciﬁ  cally for delirium and emphasizes attention, semantic com-

prehension, and nonverbal, right hemisphere cognitive functions. 
It is particularly useful in critically medically ill persons.
The Confusion Assessment Method  (CAM)
(9) is a screening tool 
to assess the presence or absence of four items from DSM-III-R delirium criteria to make a provisional diagnosis of delirium. It is especially suited to epidemiological studies and screening in high risk populations where neuropsychiatric differential diagnosis or broad phenomenological measurements are not needed. Its accuracy is enhanced if ratings are anchored by formal testing as in the CAM-ICU
(10) but is substantially reduced when used by nurses 
because they frequently miss inattention when it is present.
Psychiatrists and delirium specialists use more detailed instru-
ments  for more speciﬁ  c and sensitive detection of a broader range 
of symptoms. The Delirium Rating Scale-Revised-98 (DRS-R98)(11)
and the Memorial Delirium Rating Scale (MDAS)(12) are the most

and the Memorial Delirium Rating Scale (MDAS)(12) are the most 
widely used rating scales, and include measures of a wide breadth of symptoms. The MDAS is a severity scale used in conjunction with a DSM or ICD diagnosis whereas the DRS-R98 is both a diag-nostic and severity instrument where each item rating is anchored 
by phenomenological descriptions.
In clinically challenging situations, an EEG  can be used to help 
differentiate delirium from other neuropsychiatric disorders where generalized slowing of the dominant posterior rhythm is characteristic. Additionally, clues for speciﬁ  c disorders like com-
plex partial status epilepticus can be identiﬁ  ed.
Epidemiology and outcomes
Epidemiological studies have focused on elderly hospitalized

Epidemiological studies have focused on elderly hospitalized 
populations with far less research in younger age groups or the general population. Delirium occurs in all age groups but those at age extremes, with pre-existing cognitive impairment, cancer, and the critically ill have especially high rates. It is estimated that around 10 per cent to–15 per cent of general hospital patients have delirium upon admission with a further 10–40 per cent developing delirium during hospitalization. Overall frequency is estimated at 11 per cent to–42 per cent
(13) with the clinical rule of thumb that 
one in ﬁ  ve general hospital inpatients experience delirium at some

one in ﬁ  ve general hospital inpatients experience delirium at some 
time during hospitalization. Delirium incidence is expected to increase as demographics of the general population shift toward older ages and with higher prevalence of dementia and cerebrovas-cular and cardiovascular disorders, although improved medical care for elderly persons may offset this pattern. Presence of APOE-4 alleles may confer increased risk for poorer recovery from deliri-um, reﬂ  ecting vascular and neurodegenerative inﬂ  uences.
Delirium episodes are associated with elevated morbidity, longer 
hospital stays, greater costs of care, and higher frequency of complications.
(14) Moreover, in the elderly, reduced post hospital

(14) Moreover, in the elderly, reduced post hospital 
independence and elevated one year mortality rates occur. Although the latter is partly due to the effects of age, frailty, comorbid dementia, severity of medical comorbidities, and medication exposure, some Table 4.1.1.2  Differential diagnosis of delirium vs other common neuropsychiatric conditions
Delirium Dementia Depression Schizophrenia
Onset Acute InsidiousaVariable Variable
Course Fluctuating Often progressive Diurnal variation Variable
Reversibility FrequentlybNot usually Usually but can be recurrent Chronic relapsing and remitting course 
typical
Level of consciousness Impaired Unimpaired until late stages Generally unimpaired Unimpaired (perplexity in acute stage)
Attention/memory Inattention is primary with poor memoryPoor memory without 
marked inattention except

marked inattention except 
in end-stage illnessMild attention problems, 
inconsistent pattern – depressive 
pseudodementia, memory intact 
with formal testingPoor attention, inconsistent pattern, 
memory intact
Affect Lability No clear pattern Flattening Incongruity
Hallucinations Usually visual; can be auditory, tactile, gustatory, olfactoryCan be visual or auditory Usually auditory Usually auditory
Delusions Fleeting, fragmented, and 
usually persecutory often relate 
to immediate environment or 
impending dangerParanoid, often ﬁ  xed, relate 
to misconceptionsComplex and mood congruent 
e.g. themes of guilt or nihilismFrequent, complex, systematized, and 
often paranoid
aExcept for large strokes that can be abrupt and Lewy Body Dementia which can be subacute.
bCan be chronic (paraneoplastic syndrome, central nervous system adverse events of medications, severe brain damage).

329
epidemiological studies identify delirium as an independent 
predictor of poorer outcomes in the elderly. However, most studies have not adequately accounted for premorbid vulnerability and cognition, burden of medical problems, and pharmacological effects such that delirium may simply be a marker of underlying pathology causing poor outcomes. Delirium incidence or severity in 
the elderly can be improved by earlier specialist intervention includ-
ing the judicious use of haloperidol and more comprehensive delirium care, though the magnitude of this effect remains unclear.
Many report a new diagnosis of dementia after an episode 
of delirium.  Some evidence suggests that persistent cognitive 
impairment can occur after delirium even in those thought to be premorbidly cognitively intact
(15,16), while others ﬁ  nd that baseline

(15,16), while others ﬁ  nd that baseline 
status or medical burden predicts outcome and follow-up reveals progression of an incipient dementing process. Contributors to post delirium cognitive decline include baseline CNS vascular or neurodegenerative pathology, physical problems that also caused the delirium, toxic effects of or inability to comply and beneﬁ  t from 
treatments, unresolved delirium, an accelerating effect of delirium on cognitive decline, or possibly a direct neurotoxic effect of the delirious state itself. However, it is still unclear whether delirium plays a causal role or is simply a marker of medical morbidity and preexisting baseline vulnerabilities both of which are associated with delirium. Pharmacological effects (beneficial or adverse effects) are unaccounted for in most studies. The possibility that delirium itself is neurotoxic remains unproven, though could

theoretically involve the effects of neurochemical abnormalities 
associated with delirium (e.g. dysfunctional cellular metabolism or glutamatergic surges). Studies in younger age groups are needed to disentangle confounds from aging.
Elevated mortality  rates (ranging from 4 per cent to–65 per cent) 
during the index admission may reﬂ  ect a variety of factors including 
the impact of underlying physical causes of delirium, the consequences of reduced ability to cooperate with medical care, the complications that occur due to the delirium symptoms(e.g. pressure sores, infections, falls). Critical review of methodology 
suggests that delirium mostly carries an associated increased 
mortality risk during the year following an episode. Mortality risk is related to agedness, severity of underlying physical illness, presence of dementia, timing of diagnosis, motor presentation and 
delirium symptom severity. Mortality is elevated even when the con-

founding effects of age, medical morbidity, and medication exposure are accounted for.
(17,18)  Mortality is also elevated in hospitalized 
patients with up to four selected delirium symptoms (‘subsyndro-mal’) but without meeting syndromal criteria,
(19) highlighting the 
need for careful assessment and monitoring of patients at risk.
Risk factors
Delirium is a multifactorial condition. A typical episode reﬂ  ects the

Delirium is a multifactorial condition. A typical episode reﬂ  ects the 
cumulative effects of predisposing risk factors, individual patient vulnerabilities (including genetic), and precipitating aetiological insults. A wide range of patient, illness, and treatment variables increase the likelihood of developing delirium but preexisting cognitive impairment, any CNS disorder, age extremes, low serum albumin, and exposure to particular medications are particularly robust predictors of delirium across populations. Geriatric and paediatric medically ill patients may share risk factors such as more vulnerable cholinergic neurotransmission—related to aging effects and developmental immaturity, respectively. Some risk factors are also considered aetiologies (e.g. UTI, anticholinergic medications). 
Table 4.1.1.3 lists a variety of reported risk factors across a number 
of reports.

The interaction between predisposition (baseline vulnerability) 
and precipitating insults account for delirium incidence. Inouye and Charpentier
(20) developed a model of four common pre-
disposing and ﬁ  ve precipitating factors that predicted a 17-fold 
variation in delirium risk in elderly medical patients, which has been replicated in post-operative elderly patients.
(21) T o date most 
genetic studies have focussed on genotyes related to increased risk of alcohol withdrawal delirium, though APOE-4 allele genotype has been linked to longer duration of delirium in ICU patients.
(22)Table 4.1.1.3  Factors associated with an increased risk for delirium
1. Patient vulnerabilities
 Age extremes Pre-existing cognitive impairment e.g. dementia
 CNS disorder
 Genetic factors e.g. APOE genotype Visual deﬁ  cit
 Hearing deﬁ  cits
 Poor nutritional status
 Previous episode of delirium
2. Environmental

CNS disorder
 Social isolation Sensory extremes
 Immobility
 Novel environment Stress
 Use of restraints
 ICU stay
3. Medical
 Severe medical illness
 Burns
 HIV / AIDS Organ insufﬁ  ciency
 Infection (e.g. UTI)
 Hypoxemia
 Fracture
 Hypothermia / fever Metabolic disturbances
 Dehydration
 Elevated BUN Low serum albumin
 Nicotine withdrawal
 Increased blood-brain barrier permeability Uncontrolled pain
4. Procedure-related
 Peri-operative
 Type of surgery (e.g. hip) Emergency procedure
 Duration of operation
 Urinary Catheterization
 Artiﬁ  cial respiration
5. Drug-related
 Polypharmacy Drug / alcohol dependence
 Psychoactive drug use
 Speciﬁ  c agents (e.g. anticholinergics / opiates/ benzodiazepines)4.1.1 delirium

SECTION 4  clinical syndromes of adult psychiatry 330
Aetiology
Single-aetiology delirium is the exception with typically 3–4 signiﬁ  -
cant causative factors relevant during any single episode which interact and overlap sequentially to produce or sustain delirium symptoms. It is crucial that potential aetiologies are constantly reevaluated throughout a delirium episode and even after a single cause is identiﬁ  ed, efforts to unearth other factors should continue. 
Categories of delirium aetiologies include drug intoxication, drug withdrawal, metabolic/endocrine, traumatic brain injury, seizures, intracranial infection, systemic infection, intracranial neoplasm, extracranial neoplasm, cerebrovascular disorder, organ insufﬁ  ciency, 
other CNS disorder, and other systemic factors (heat stroke, 
radiation, hypothermia, etc). Table 4.1.1.4 lists clinical investiga-
tions recommended in routine evaluation of delirium and addi-tional tests indicated in particular cases.

Among the most common causes are infections and those related 
to illicit and prescribed drugs and alcohol, either in toxicity or withdrawal. Additionally, when serum albumin levels are low, more unbound drug is available to cause adverse events. Increased blood-brain barrier permeability (e.g. uremia, sepsis) can allow passage of drugs that ordinarily do not cross into the brain and delirium can result.
Neuropathogenesis
Delirium reﬂ  ects a generalized disturbance of brain function as 
evidenced by the broad range of neuropsychiatric symptoms, diffuse slowing on EEG, and widespread alterations in cerebral blood ﬂ  ow.
(23) Despite the range of underlying aetiologies, delirium presents with a relatively consistent clinical proﬁ  le and is thus 
considered a unitary syndrome reﬂ  ecting a ﬁ  nal common neural

considered a unitary syndrome reﬂ  ecting a ﬁ  nal common neural 
pathway for multiple diverse causes and pathophysiologies.(24,25)
When studying delirium pathophysiology, it is important to distin-guish between physiological mechanisms of aetiologies and neural pathology in the CNS that leads to characteristic delirium symp-toms. Figure 4.1.1.1 offers examples of areas to distinguish.
Many functions are typically not disturbed in delirium (e.g. pri-

mary motor or sensory functions) and certain neuropsychological functions are disproportionately impaired (e.g. attention) suggest-ing that particular neurobiological underpinnings are relevant to delirium neuropathogenesis. Neuroimaging and neuropsycho-logical studies suggest involvement of prefrontal cortex, thalamus, nondominant posterior parietal and fusiform cortices, and sub-cortical regions, especially right-sided pathways.
(24) Additionally, 
anterior and posterior portions of cingulate cortex may be involved in Cognition and Higher Level Thinking domains, while subcortical regions including thalamus, hypothalamus, basal fore-brain and brainstem may be involved in the Circadian Rhythm domain. Other features may be related indirectly to the underlying brain disturbances that cause domain abnormalities.
Evidence from preclinical studies, causation (e.g. exposure to

Evidence from preclinical studies, causation (e.g. exposure to 
anticholinergic and dopaminergic deliriogenic agents), direct studies of pathophysiology, and treatment with dopamine blockers point to a relative cholinergic deﬁ  cit and dopaminergic excess 
as the principal neurochemical disturbances underpinning delirium although other neurochemical systems (e.g. serotonergic, glutamateric, GABAergic, noradrenergic) are clearly implicated in delirium due to particular aetiologies, perhaps through their inter-
actions with dopaminergic and cholinergic systems. Synaptic, axo-
nal and glial abnormalities are implicated.
Altered oxidative metabolism, stress axis activation, and neuro-
inﬂ ammatory mechanisms may acutely impact neurotransmission.

inﬂ ammatory mechanisms may acutely impact neurotransmission. 
Further, neurostructural derangements previously thought to occur in chronic neurodegenerative disorders can occur acutely and tran-siently, and may underlie delirium. These include traumatic hyper-phosphorylation during anaesthesia or traumatic elevations of Abeta inducing synaptic morphological and functional alterations. 
Fig. 4.1.1.1. Examples of different aetiologies for delirium and a variety 
of pathophysiological mechanisms that can then alter brain function. The neuropathogenesis of delirium involves dysfunction of brain regions and circuitry which may ultimately result in characteristic symptoms of delirium despite a wide variety of aetiologies and pathophysiological insults to the brain.Aetiologies Pathophysiologies CNS Neuropathogenesis
•Hypoxemia
•Hepatic failure
•Infection
•Surgery-related
•Trauma

•Trauma
•Medications•Cytokines
•Low oxygenation
•Reduced
perfusion
•Axonal damage
•Excess Abeta•Neurotransmitter
activity
•Neural circuitry 
•Thalamic gating
•Glia
•Synaptic function
•Neurone destruction
Table 4.1.1.4  Clinical investigations recommended for delirium
1. Mandatory (recommended for all patients)
 Full blood count and differential
 Urea and electrolytes to include Mg, Ca, Po4
 Renal function Liver function tests to include serum albumin
 Urinalysis
 Random blood glucose Electrocardiogram
 Chest X-Ray
2.  As indicated (according to particular clinical circumstances—list not 
exhaustive)
 Drug screen (therapeutic and illicit) Blood alcohol concentration
 Blood cultures
 Cardiac enzymes Arterial blood gases
 Serum Folate / B12
 Thyroid function tests Erythrocyte sedimentation rate
 Cerebrospinal ﬂ  uid examination
 Syphilis serology
 CT brain MRI brain
 Electroencephalography (with nasopharyngeal leads)

Serum Folate / B12
 Polysomnography
 Prothrombin time Urinary porphyrins Screen for heavy metals and insecticides

331
The broad disturbance of CNS function that occurs in delirium 
inevitably involves alterations to many cortical and subcortical regions and their neural circuitry, via both direct and indirect (diaschesis) effects.
Management
Delirium is a medical urgency, yet the value of timely intervention in limiting the many deleterious effects of a delirium episode is underappreciated. Optimal management requires the collaborative efforts of primary treating physicians and nursing staff with deliri-um specialists. Both the underlying causes and the brain disorder need simultaneous assessment and treatment. Careful attention to reorientation strategies (e.g. clearly visible clock/calendar), safety in immediate surroundings and optimal level of environmental stimulation (e.g. natural levels of diurnal lighting) are fundamental to the management of delirium across treatment settings and populations.
(26) Relatives / loved ones can report changes in behav-

iour and mental state (‘not themselves’) and provide collateral information about baseline cognitive and independent functioning and risk factor exposure.
Delirium prevention  using multicomponent interventions to 
address modiﬁ  able risk factors can reduce the frequency and 
severity of delirium in elderly medical and post-operative populations.
(27,28) Common elements include elimination of 
unnecessary medications, careful attention to hydration and nutri-tional status, pain relief, correction of sensory deficits, sleep enhancement, early mobilization, and cognitive stimulation. Careful attention to reorientation strategies (e.g. clearly visible clock/calendar), safety in immediate surroiundings and optimal level of environmental stimulation (e.g. natural levels of diurnal lighting) are key elements of delirium care.
(26)
Recent studies of pharmacological prophylaxis of delirium

(26)
Recent studies of pharmacological prophylaxis of delirium 
in high-risk populations have been encouraging. Controlled studies using haloperidol,
(29) olanzapine,(30) donepezil(31) and riv-
astigmine(32) report signiﬁ  cant reductions in delirium incidence, 
severity and/or duration.
(a) Pharmacological management

Pharmacological management of delirium addresses the brain dysfunction itself while the underlying medical problems are being separately considered. This is akin to acute heart failure where treatment of cardiac function is concurrent with management of the aetiologies for the organ failure. Pharmacological manage-ment of delirium is based on empirical knowledge drawn from case reports, open label prospective studies and a small number of randomized trials some of which are comparator studies. Adequately powered double blind randomized placebo-controlled efficacy trials are needed because there is currently no medication with an indication for delirium treatment by any regulatory authority. The inherent ﬂ  uctuating nature, varying duration, spontaneous recov-

ery rate, and impact of medical treatments upon underlying causes render placebo-controlled studies especially important in evaluat-
ing therapeutic interventions. Nevertheless, there are over 20 well-
conducted prospective studies of antipsychotic agents used in acute treatment of delirium where more than two-thirds of treated delirious patients experience clinical improvement, typically within a week.
(33) A randomized controlled trial of haloperidol vs 
olanzapine vs non-drug treatment in elderly patients indicated similar response rates in those receiving haloperidol (87.5 per cent) and Olanzapine (82 per cent), which was signiﬁ  cantly greater 
than those in the non-drug treatment group (31 per cent).
(34)

(34)
Treatment response includes improved cognitive and noncognitive symptoms of delirium and does not appear to be closely linked to antipsychotic effect or sedative action. Y ounger patients with hyperactive presentations and patients without comorbid dementia respond more robustly to antipsychotics, but hypoactive patients also improve and deserve treatment given that delirium com prises many serious symptoms besides challenging motor behaviour.
(35,36)
Most pharmacological strategies are based upon the prevailing 
notion of a relative dopaminergic excess and cholinergic deﬁ  ciency 
as the principal neurochemical aberrations underlying delirium, and agents with either procholinergic or antidopaminergic effects are favoured. Haloperidol  remains the standard agent used to treat

as the principal neurochemical aberrations underlying delirium, and agents with either procholinergic or antidopaminergic effects are favoured. Haloperidol  remains the standard agent used to treat 
delirium and is available in oral, intramuscular, and intravenous preparations. However, intravenous haloperidol does not have any indicated use by a regulatory agency and carries a high risk for QTc prolongation and torsades de pointes tachyarrhythymia that can lead to sudden death. Suggested haloperidol doses are 1–2 mg every four hours as needed but with lower doses (e.g. 0.25–0.5 mg every four hours) in the elderly, very frail, or populations with neurolep-tic sensitivity—APA guidelines, 1999.
(37) Uncontrolled agitated

(37) Uncontrolled agitated 
delirium can be life threatening especially in critically ill intensive care unit patients where substantially higher doses have been reported without major adverse effects. Careful monitoring of ECG (telemetry with intravenous haloperidol), and maintaining normal serum potassium, calcium, and magnesium levels are recommended.
Accumulating evidence supports the use of atypical antipsychotic 
agents  in delirium (risperidone, olanzapine, quetiapine, aripirazole, 
ziprasidone, amisulpiride). Comparison studies suggest similar response rates to haloperidol for both risperidone and olanzapine but with reduced extrapyramidal side effects. In highly agitated patients where sedation is desirable, more sedative agents or com-bination with lorazepam may be considered. Given the importance of sleep-wake cycle disturbances in delirium, dose scheduling should encourage recovery of normal sleeping patterns.

Benzodiazepines  can act as either an alleviating or as a risk factor 
for delirium depending on the circumstances of exposure. Benzodiazepines can be associated w ith worsening of me ntal state
(38)
and increase delirium risk in ICU(39) and cancer patients.(40)
Moreover, therapeutic effects vary from anxiolytic to sedative 
to hypnotic with ascending doses. Conversely, benzodiazepines are first line treatment for delirium related to sedative and alcohol-withdrawal or seizures. Benzodiazepines can allow for lower neuroleptic doses where intolerance is a problem or where extra sedation is desired. Lorazepam is preferred due to its short acting nature and relatively predictable bioavailability when given intramuscularly. Lower doses are required in the elderly and those with respiratory or hepatic compromise or receiving drugs that undergo extensive hepatic oxidative metabolism. Unwanted effects of benzodiazepines can be rapidly reversed with ﬂ  umazenil.

The use of procholinergic agents  such as intravenous physostig-
mine has long been advocated for delirium due to toxicity with 
anticholinergic drugs, but routine delirium use is limited by 
gastrointestinal side effects, cardiac arrythmia and seizures. T o date there has been limited study of newer procholinergics in part because their long half-lives preclude reaching steady state for use 4.1.1 delirium

SECTION 4  clinical syndromes of adult psychiatry 332
in acute conditions, in contrast to parenteral physostigmine’s fast 
onset of action.
Anecdotal evidence also exists for the use of mianserin, traza-
done, melatonin, psychostimulants, and even ECT in the treatment of delirium but these strategies are not well-studied or applied in routine clinical practice.
(b) Risks, beneﬁ  ts, and dosing
Adequate drug treatment of delirium is limited by concerns over 
potential toxic effects in highly morbid, frail elderly whose delirium may actually herald bad outcome from medical illness. In assessing the risk-beneﬁ  t ratio of medication use one must consider the risk 
of nontreatment of delirium given its grave consequences. Dosing needs to take into account structural degenerative changes, reduced neurochemical ﬂ  exibility, less robust counter-regulatory homeo-

static mechanisms, reduced renal and hepatic function, lower water to fat ratio with reduced muscle mass, and reduced plasma esterase activity. In hypoactive or mechanically ventilated patients careful dose titration can be assisted by regular monitoring of sedation. With sedation, a beneficial effect of catching up from sleep deprivation also needs to be considered. Adverse events such as Parkinsonism or akathisia can be misattributed to agitation of delirium, though are uncommon in treatment studies perhaps 
reﬂ ecting a protective effect of the hypocholinergic state that fre-

quently underpins delirium. The potential for cardiac arrythmias can be reduced with ECG monitoring in high dose or intravenous haloperidol use or where patients have a cardiac history or baseline ECG shows QTc interval >450 mSec.
(c) Patients with concomitant dementia
Both pharmacological(35) and non-pharmacological strategies(28)
appear less effective in patients with concomitant dementia 
perhaps reﬂ  ecting the inherently poor outcome of elderly dement-
ed populations with high physical comorbidity. There are concerns regarding the small but increased risk of cerebrovascular events in demented patients chronically receiving neuroleptics, but the relative risks of short-term use in delirium must be proportional-ized against potential beneﬁ  ts. Lower doses should be used with 
careful monitoring for adverse effects and more prolonged use should not occur in the absence of clear beneﬁ  ts.

(d) Management after recovery
Depending on the degree of memory imprinting during an 
episode, patients experience signiﬁ  cant emotional distress after 
recovery(41) and many continue to have distressing recollections of 
delirium six months later, especially where the episode has involved psychotic symptoms. For families, disturbing recollections of ﬁ  nal 
contacts with loved ones can be enduringly distressing and associ-ated with complicated bereavement reactions. Some patients mini-mize their experiences fearing that they represent emerging senility or loss of competence. Explicit recognition allows clariﬁ  cation 
of the causes of delirium and reduction of future risk factors.
Delirium is a complex neuropsychiatric syndrome that occurs commonly across all age groups and healthcare settings. Signiﬁ  cant

Delirium is a complex neuropsychiatric syndrome that occurs commonly across all age groups and healthcare settings. Signiﬁ  cant 
adverse outcomes of delirium are increasingly recognized and can be reduced by a more consistent approach to detection that empha-sizes disturbances of attention. Optimal management requires the collaborative efforts of carers and healthcare staff and judicious 
use of pharmacological and nonpharmacological strategies that concurrently manage underlying physical causes and the delirium itself. Greater clarity is needed regarding the prognostic relation-ship to dementia, phenomenology of prodromal, subsyndromal and syndromal delirium, and how risk factors, vulnerabilities, and treatment may vary across populations and treatment settings.
The European Delirium Association  advocates for better research and aims

The European Delirium Association  advocates for better research and aims 
to foster research activity across all disciplines. Annual meeting details, educational materials and a discussion forum are available at www.europeandeliriumassociation.com
A US-based delirium organization aims to foster delirium care and research 
in critically ill patients and includes various teaching resources including protocols for assessment and treatment at www.icudelirium.org
The American Psychiatric Association website includes detailed delirium 
treatment guidelines, a quick reference guide as well as a patient and 
family guide (see www.psych.org/psych_pract/treatg/quick_ref_guide/DeliriumQRG_4-15-05.pdf)
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4.1.2 Dementia: 
Alzheimer’s disease
Alzheimer’s disease ( AD) and other dementias incur huge costs to

Alzheimer’s disease ( AD) and other dementias incur huge costs to 
society, to the families of those affected, and to the individuals themselves. Costs to society include both direct costs to health and social services and indirect economic costs in terms of lost produc-tivity, as carers are taken out of the workplace, and the economic costs to those families caring for or funding the care of their rela-tive. Increasingly, as treatments become available, these costs are targets for change and are part of the cost–beneﬁ  t analysis of new 
compounds, especially the largest single direct cost, that of the provision of nursing and other forms of continuing care. Apart from the ﬁ  nancial cost to families there is the emotional impact 
resulting in distress and psychiatric morbidity.
As the population ages, these costs pose substantial social and 
economic problems. Although lifespan itself has remained static,

economic problems. Although lifespan itself has remained static, 
the numbers of elderly in both developed and developing societies 
is increasing rapidly. In the developed world the sharpest projected growth is in the very elderly cohort—precisely the one that is at most risk of AD. Within the developing world, the total number of elderly people is projected to rise substantially, reﬂ  ecting to a

large part better child health and nutrition. For countries in South America and Asia, with large and growing populations, the costs involved in caring for people with dementia in the future will become an increasing burden on health and social services budgets. In the absence of such services families will inevitably shoulderthe main part of providing care, although the very process of devel-opment is associated with increasing urbanization and, to some 4.1.2 dementia: alzheimer’s disease

SECTION 4  clinical syndromes of adult psychiatry 334
degree, a diminution of the security provided by extended family 
structures.
From discovery towards understanding
In the early part of the twentieth century, Alois Alzheimer described his eponymous disorder in a middle-aged woman who suffered not only cognitive deterioration and functional decline but psychotic experiences, including delusions and auditory hallucinations. Neuropathology included gross atrophy and plaques and tangles on microscopy. Although all the important features of AD were described at this stage, two important developments came much later. First, in the 1960s with the studies of Roth and colleagues in Newcastle
(1) and others elsewhere, it was appreciated that much

(1) and others elsewhere, it was appreciated that much 
dementia in the elderly has an identical neuropathological appear-ance to that of AD in younger people. The other development was the rediscovery that AD has a rich phenomenology. The non-cognitive symptomatology of AD is integral to the clinical manifes-tation of this disease, and is a major cause of carer burden and medical intervention. This second phase of research—the recogni-tion that both the neuropathology and clinical phenomenology described by Alzheimer occur in what had previously been though of as senile dementia or, worse, just ageing, was accompanied by a growing understanding of the neurotransmitter deﬁ  cits in AD. 
The cholinergic hypothesis provided the ﬁ  rst glimpse of possible 
interventions, and remains the most important ﬁ  nding from this 
period of AD investigations. The third phase of AD research encompasses the use of molecular approaches to understanding

period of AD investigations. The third phase of AD research encompasses the use of molecular approaches to understanding 
pathogenesis. The techniques of molecular biology have been 
applied to understanding the formation of plaques and tangles, to a growing understanding of the genetic aetiology of much of AD, and, through the use of transgenic approaches, to developing animal and cellular models of pathogenesis.
Just as research can broadly be seen to have three phases—discovery, 
neuropathology, and molecular aspects—so too does the clinical response to AD. For many years cognitive impairment in the elderly was perceived as senility. As a process thought to be an inev-itable consequence of ageing it was difﬁ  culty to establish medical-

care models. Hence the needs of the elderly with AD were not seen as requiring specialist intervention, carers needs were not realized, and public appreciation of the impact of dementia on the elderly themselves or on the family was negligible. The change in percep-tion of AD from ‘just ageing’ to a disease was accompanied, and to some degree led, by the development of ‘old-age psychiatry’ as a specialism on the one hand and by the rapid growth of the AD societies on the other. During this second phase of AD treatment, the goals have been to ensure that the care needs of patients are met, that families’ concerns are addressed, and that behavioural disturbance is minimized. The third phase of AD treatment began with the arrival of speciﬁ  cally designed interventions. Compounds 
have been introduced that were designed to ameliorate some of the deﬁ cits incurred by the disease process, and other approaches are 
being developed to treat those disease processes themselves.

Cognitive impairment
Dementia is acquired cognitive decline in multiple areas resulting in functional impairment; AD is one cause of dementia and the core clinical symptom of AD is cognitive loss. However, as noted 
above, AD is clinically heterogeneous and includes diverse non-cognitive symptoms. Cognitive decline is manifested as amnesia, 
aphasia, agnosia, and apraxia (the 4As).
(a) Amnesia
Memory loss in AD is early and inevitable. Characteristically, recent 
memories are lost before remote memories. However, there is considerable individual variation, with some patients able to recall speciﬁ  c and detailed events of childhood and others apparently

memories are lost before remote memories. However, there is considerable individual variation, with some patients able to recall speciﬁ  c and detailed events of childhood and others apparently 
having few distant memories accessible. With disease progression, even remote and emotionally charged memories are lost. The dis-crepancy between recent and remote memory loss suggests that the primary problem is of acquisition or retrieval of memory rather than a destruction of memory, and this is conﬁ  rmed in early AD,
(2)
although as the disease progresses it is likely that all memory pro-
cesses are impaired. Retrieval of remote memory is assumed to be preserved for longer because of rehearsal over life.
(b) Aphasia
Language problems are found in many patients at presentation, although the language deﬁ  cits in AD are not as severe as those of 
the fronto-temporal degenerations
(3) and may only be apparent on 
detailed examination. Word-ﬁ  nding difﬁ  culties (nominal dyspha-

sia) are the earliest phenomena observed and are accompanied by circumlocutions and other responses, for example repetitions and alternative wordings. As the disorder progresses, syntax is affected and speech becomes increasingly paraphasic. Although harder to assess, receptive aphasia, or comprehension of speech, is almost certainly affected. In the ﬁ  nal stages of the disorder, speech is grossly 
deteriorated with decreased ﬂ  uency, preservation, echolalia, and 
abnormal non-speech utterances.
(c) Agnosia
Patients with AD may have difﬁ  culty in recognizing as well as nam-

ing objects. This can have implications for care needs and safety if the unrecognized objects are important for daily functioning. One particular agnosia encountered in AD is the loss of recognition of one’s own face (autoprosopagnosia). This distressing symptom is the underlying cause of perhaps the only clinical sign in AD—the mirror sign. Patients exhibiting this will interpret the face in the mirror as some other individual and respond by talking to it or by apparent fearfulness. Autoprosopagnosia can present as an apparent hallucinatory experience, until it is realized that the ‘hallucination’ is ﬁ  xed in both content and space, occurring only 
when self-reﬂ  ection can be seen.
(d) Apraxia
Difﬁ culties with complex tasks that are not due to motor impair-

ment become apparent in the moderate stages of AD. Typically, difﬁ culties with dressing or tasks in the kitchen are noticed ﬁ  rst, 
but these are inevitably preceded by loss of ability for more difﬁ  cult 
tasks. Strategies to avoid such tasks are often acquired as the disease progresses, and it is only when these fail that the dyspraxia becomes 
apparent.
Other cognitive impairment
There appear to be no cognitive functions that are truly preserved 
in AD. Visuospatial difﬁ  culties commonly occur in the middle stages 
of the disorder and may result in topographical disorientation,

335
wandering, and becoming lost. Difficulties with calculation, 
attention, and cognitive planning all occur.
Functional impairment
Although the cognitive decline in AD is the core symptom, it is the functional deterioration that has the most impact on the person themselves and it is the functional loss that necessitates most of the care needs of patients with AD, including nursing-home residency.
(4)
Increasingly, abilities to function in ordinary life (activities of daily living ( ADLs )) are lost, starting with the most subtle and easily 
avoided and progressing to the most basic and essential. In general, functional abilities decline alongside cognitive abilities. However, the precise correlation between these functions is not perfect, suggesting that factors other than disease severity account for part of the variance between patients.
(5) Functional abilities are related to

(5) Functional abilities are related to 
gender; for example, cooking abilities are rehearsed more frequently in women, and home-improvement skills in men. However, the over-all pattern shows some similarities between groups of patients with similar disease severity. This is exploited in the Functional Assessment Staging ( FAST ) Scale;
(6) in the original form, this is a seven-point 
scale of functional impairment, with stage 1 as no impairment and 
stage 7 as severe AD. A sequential decline is mapped by descriptions 
of the abilities that are lost: stage 2, difﬁ  culties with language and 
ﬁ nding objects; stage 4, difﬁ  culties with ﬁ  nances; stage 6, inconti-
nence and inability to dress or wash oneself.
ADLs are divided into those that relate to self-care and those that 
concern instrumental activities. Instrumental ADLs, those related to the use of objects or the outside world, are lost ﬁ  rst and can be 
subtle.
(7) A change in the ability to use the telephone properly or to

subtle.
(7) A change in the ability to use the telephone properly or to 
handle ﬁ  nances accurately may not be apparent. Self-care ADLs 
include dressing and personal hygiene and are also lost gradually; for example, untidiness in clothing progresses to difﬁ  culties in 
dressing. Personal hygiene becomes poor as dentures are not cleaned and baths taken less often, before ﬁ  nally assistance is 
required with all self-care tasks.
Neuropsychiatric symptoms
(a) Mood
The relationship between AD and depression is complex. Depression is a risk factor for AD, depression can be confused with dementia (pseudodementia), depression occurs as part of demen-tia, and cognitive impairments are found in depression. Depression occurring as a symptom of dementia will be considered here. Assessing the mood of a person with dementia is difﬁ  cult for obvi-

ous reasons. However, psychomotor retardation, apathy, crying, poor appetite, disturbed sleep, and expressions of unhappiness all occur frequently. The rates of depression found in cohorts of patients with AD vary widely, reﬂ  ecting changes in prevalence 
at different levels of severity and difﬁ  culties in the classiﬁ  cation 
of symptoms suggestive of depression in those with cognitive loss. A major depressive episode is found in approximately 10 per cent of patients, minor depressive episode in 25 per cent, some features of depression in 50 per cent, and an assessment of depression by
a carer in up to 85 per cent.
(8–12)  It is commonly believed that 
depression is more common in the early than in the later stages of AD, although this may reﬂ  ect the difﬁ  culties of assessing depression in 
the more severely affected and least communicative patients. Indeed, severely affected patients in nursing homes may be particularly prone to depression.

(13) Elation, disinhibition, and hypomania all occur 
in AD but are relatively infrequent, elevated mood being found in only 3.5 per cent of patients by Burns et al.
(10)
The underlying cause of mood change in AD is not known. 
However, loss of serotonergic and noradrenergic markers accom-panies cholinergic loss; some studies have found a greater loss of these markers at post-mortem in AD patients with depression than in non-depressed patients.
(14–16)
(b) Psychosis
Psychotic symptoms occur in many patients, although, as with depression, there is an inherent difﬁ  culty in determining the pres-

(14–16)
ence of delusions or hallucinatory experiences in the moderately to severely demented. In community-based surveys, between 20 and 70 per cent are reported to suffer from some form of psychotic symptom with delusions being more common than hallucina-tions.
(11,17,18) Delusions are frequently paranoid and the most 
common delusion is one of theft. In the context of the confusion and amnesia of dementia, it is easy to appreciate how the experi-ence of mislaying an object becomes translated into conviction of a theft. Other patients become convinced that someone, often a family member, is trying to harm them.
Hallucinations are only somewhat less frequent than delusions—
the median of one series of studies being 28 per cent.
(19) Visual

(19) Visual 
hallucinations are reported more commonly than auditory ones, and other modalities are rare. Most studies of the non-cognitive symptomatology of AD precede the wide recognition and accepted criteria of dementia with Lewy bodies, one of the cardinal symp-toms of which is visual hallucinations. It is probable that a large number of those AD patients experiencing visual hallucinations reported in the studies would now be classiﬁ  ed as having dementia 
with Lewy bodies.
Phenomena falling short of delusions or hallucinations, such as 
persecutory ideas or intrusive illusionary experiences, are common in AD as are misidentiﬁ  cation syndromes. Capgras’ syndrome may 
occur, but frequently the symptom is less fully evolved with the patient mistaking one person for another. Failure to recognize one’s

occur, but frequently the symptom is less fully evolved with the patient mistaking one person for another. Failure to recognize one’s 
own face may be due to visuospatial difﬁ  culties or to a true misiden-
tiﬁ cation syndrome—distinguishing between the two is difﬁ  cult.
Various factors have been associated with psychosis in AD, but few 
have been substantiated in multiple studies. Burns et al.
(20) found 
that more men than women suffered delusions of theft, although others ﬁ  nd that psychosis occurs more often or earlier in women. An 
association with polymorphic variation in serotonin receptors has been reported.
(21–23) The relationship between psychosis and demen-
tia severity is not as clear cut as that between functional ability and dementia severity. Psychosis can occur at any stage of the disease process, although most studies ﬁ  nd the maximal rate of psychosis in 
those with at least moderate dementia.
Although the biological basis of psychosis within AD is not

Although the biological basis of psychosis within AD is not 
fully understood,
(14) it is clear that psychosis symptoms impact 
upon carers causing increased distress,(24,25) and that underlying 
psychosis accounts for much of the behavioural disturbance and aggression encountered in AD.
(26)
(c) Personality
Changes in personality are an almost inevitable concomitant of AD. Indeed, it is difﬁ  cult to envisage how profound cognitive 
impairment resulting in the loss of recognition of loved ones, and 4.1.2 dementia: alzheimer’s disease

SECTION 4  clinical syndromes of adult psychiatry 336
an understanding of and ability to react with the outside world, 
could not result in a change in personality. Family members have described the loss of personality as a ‘living bereavement’—the body remains, but the person once known has gone. Personality change is most frequently one of loss of awareness and normal responsiveness to the environment. Individuals may become more anxious or fearful, there is a ﬂ  attening of affect, and a withdrawal 
from challenging situations. Catastrophic reactions are short-lived emotional reactions that occur when the patient is confronted, and cannot avoid, such a challenging situation. Less commonly, person-ality changes may be of disinhibition with inappropriate sexual behaviours or inappropriate affect. Aggressiveness is, as noted above, often accompanied by psychosis, but it may be part of a more general personality change.
(d) Other behavioural manifestations

Behavioural complications in AD have become a target of therapy. However, the term encompasses a wide range of behaviours, some of which include neuropsychiatric syndromes, some caused by neuropsychiatric syndromes, and some of which have little apparent relationship to mood or to thought content. Behavioural complication is itself a largely subjective term that relies to a great extent on informer evaluation: but behaviour may be a complica-tion in one context, although not in another.
Behaviours exhibited in AD include wandering, changes in 
eating habit, altered sleep or circadian rhythms, and incontinence. These behaviours are closely linked to disease severity and occur to some extent in the majority of patients with AD. Wandering may be a manifestation of topographical confusion, a need for the toilet, or it may reﬂ  ect hunger, boredom, or anxiety. Sleep is frequently 
disturbed, with many patients exhibiting altered sleep–wake cycles

disturbed, with many patients exhibiting altered sleep–wake cycles 
and others experiencing increased confusion towards evening (‘sundowning’). A central defect in the regulation of circadian rhythms underlying these phenomena is postulated.
(27) Excessive 
or inappropriate vocalizations (grunting and screaming) occur in the late stages.
Classiﬁ  cation
Alzheimer’s disease is classiﬁ  ed, as with all other disorders, by 
DSM-IV and by ICD-10. In addition, it also has a specialized clas-sification system resulting from the National Institute of Neurological and Communicative Disorders and Stroke–AD and Related Disorders Association ( NINCDS–ADRDA ).
(28) This clini-
cal diagnostic system is internationally accepted and widely observed. There are also classiﬁ  cation systems for neuropathologi-
cal diagnosis, most notably the Consortium to Establish a Registry for AD ( CERAD ) criteria.
(29)
DSM-IV stipulates that a dementia syndrome is characterized

(29)
DSM-IV stipulates that a dementia syndrome is characterized 
by deterioration in multiple cognitive deﬁ  cits, including amnesia, 
resulting in functional impairment. A gradual onset and decline in the absence of other conditions sufﬁ  cient to cause dementia 
indicates AD. ICD-10 shares with DSM-IV the deﬁ  nition of a 
dementia syndrome and notes that an insidious onset and slow decline in the absence of other disorders sufﬁ  cient to cause demen-
tia indicates AD. The NINCDS–ADRDA criteria deﬁ  nes possible, 
probable, and deﬁ  nite categories; the latter being restricted to neu-
ropathological conﬁ  rmation of a clinical diagnosis.
(28) It is impor-
tant to note that both clinical and neuropathological data are required—no single neuropathological lesion is pathognomonic of

tant to note that both clinical and neuropathological data are required—no single neuropathological lesion is pathognomonic of 
AD, and it is still uncertain how often or to what extent the neuro-pathological lesions of AD also occur in normal ageing.
(30) Probable 
AD, according to NINCDS–ADRDA, requires a dementia with pro-gressive decline in memory and other cognitive areas, cognitive impairment established by formal testing, no disturbance of consciousness, and absence of other disorders sufﬁ  cient to cause 
dementia. Supporting features include decline in function, change in behaviour, positive family history, and decline in speciﬁ  c cogni-
tive areas including aphasia, apraxia, and agnosia. Non-speciﬁ  c 
change on electroencephalography ( EEG ) and progressive changes

change on electroencephalography ( EEG ) and progressive changes 
on CT are supporting, but not necessary, features. Possible AD should be diagnosed if there are variations in the clinical presenta-tion, another disorder sufﬁ  cient to cause a dementia (even if it is 
not thought to do so in this case), or a restricted cognitive decline.
A number of studies have attempted to determine the accuracy 
of diagnostic criteria against post-mortem diagnosis. One of the 
difﬁ culties in these studies is that because AD is the most common 
dementia (by some way), such studies are very likely to ﬁ  nd a high-
positive predicative value. Kukull et al.
(31) found the speciﬁ  city of 
DSM-III to be higher than NINCDS–ADRDA (0.8 versus 0.65), but NINCDS–ADRDA had a higher sensitivity (0.92 versus 0.76), Mok et al . ﬁ nd broadly similar ﬁ  ndings for both primary care 
physicians and for neurologists;

(32) some others ﬁ  nd an even lower 
speciﬁ  city.(33)
Diagnosis
Alzheimer’s disease is the most common of the dementias, occur-
ring in some 60 to 70 per cent of cases. However, this oft-stated ﬁ gure must be treated with some caution for two reasons. First, 
cases that come to post-mortem represent a biased sample and in the community a large proportion (up to a third) of non-demented individuals have pathological signs of AD such as neuritic plaques.
(30) Second, even at post-mortem the distinction between

(30) Second, even at post-mortem the distinction between 
different dementias is not clear cut—many AD brains show the presence of Lewy bodies and others have considerable evidence of vascular damage. The proportion of mixed pathologies is actually rather high, between 15 and 30 per cent of all dementias. Thirdly, even the gold-standard of neuropathological diagnosis is not infal-lible. Neuropathologists show a very high degree of inter-rater agreement on the diagnosis of probable AD and Dementia with Lewy Bodies (DLB) but a rather lower rate of agreement when there is vascular damage, when the diagnosis is of fronto-temporal dementia (FTD) and on the more equivocal cases of AD.
(34)
History

(34)
History
Making a clinical diagnosis of AD is a positive process and not one of exclusion. The most valuable diagnostic assessment is a careful informant history, paying attention to the pattern and timing of onset and progression. In the research context, a family history interview conducted by telephone provides a degree of accuracy compatible with a full clinical assessment.
(35) Detailed semi-structured 
family informant diagnostic schedules are available, such as Cambridge Mental Disorders of the Elderly Examination (CAMDEX).
(36) A history should be taken for the presence of risk 
factors for AD (e.g. a positive family history) and vascular and other risk factors (e.g. hypertension and head injury). Taking a family history for late-onset disorders such as AD requires special

337
attention. Because of attrition due to other illness, many elderly 
people have had too few relatives reach the age of onset of demen-tia to make a pedigree analysis informative. The ages at death of all relatives should be established, together with cause of death and the presence or absence of dementia or memory problems in late life. The term ‘sporadic’ dementia should be avoided, and is mis-leading when applied to an individual with a dementia where one parent died young and where no sibling reached the age of 65 to 70 years. The history should also screen for the presence of other illnesses sufﬁ  cient to cause a dementia and for systemic health 
in general. The presence of any signiﬁ  cant physical illness, from 
chronic pain to delirium, may signiﬁ  cantly alter cognitive abilities 
in the elderly, and especially so in those with AD.
A careful history should also establish the presence of any behav-
ioural disturbance that has occurred. The relationship of aggres-

sion, wandering, agitation, or other behaviours to care tasks and other recent changes in the provision of the care package should be established. As the mainstay of the management of behavioural disturbance in all dementias is behavioural, establishing the antecedents to behaviour is an absolute prerequisite to effective management.
Examination
In addition to an examination of the mental state to establish the presence of disorders of mood and thought content, the examina-tion will establish the speciﬁ  c pattern of cognitive impairment and 
the degree of impairment. Screening tests used to establish the presence of cognitive impairments include the Mini Mental State Examination;
(37) this is a 30-point scale routinely used in all

(37) this is a 30-point scale routinely used in all 
clinical trials of drugs for the treatment of AD, which is also a use-ful proxy measure for severity. It should be accompanied by other cognitive testing, including supplementary examination for apha-sia and apraxias. Other cognitive and physical examinations will be necessary where the differential diagnosis is between a lobar dementia (e.g. FTD) or a subcortical dementia (e.g. that accompa-nying Huntington’s disease).
In addition to the cognitive examination, a physical examination 
should be conducted in all patients with AD, although this might not be most effectively and conveniently performed at the initial assessment. Physical illness, including chronic pain, infection, cardiac insufﬁ  ciency, or anaemia are all common in the elderly and

can both complicate the diagnosis of AD and increase confusion in 
those known to have AD.
Assessment of function
Clinical assessment of function can be performed by informant 
history and by direct observation. Key to an assessment of function is a careful informant history seeking to establish where there has been a functional decline and remembering that instrumental ADLs are lost before basic activities. Instrumental ADLs are highly individual and require careful interviewing to assess—one patient may have a modest decline in their ability to use information tech-nology whilst another may have trouble using all the appropriate settings on the central heating. The occupational therapist fulﬁ  ls an 
invaluable role in establishing the detailed functional ability of those with AD, in addition to implementing changes in the home designed to maximize function. The FAST Scale
(6) is based on the

(6) is based on the 
premise that the pattern of decline in function is relatively uniform in AD, and hence establishes a staging of severity on function rather than cognition. As in most instances functional severity is 
of more relevance for the provision of services, there is much to recommend such an approach. Scales used in research that can also be usefully employed in the clinic include the Bristol ADL Scale
(38)
and the Disability Assessment for Dementia.(39)
Global assessment
Driven largely by the United States Food and Drugs Administration, global assessment has become part of the assessment of all patients 
with AD in clinical trials and is ﬁ  nding its way into clinical practice.

with AD in clinical trials and is ﬁ  nding its way into clinical practice. 
The underlying premise is that an assessment by a clinician, often supplemented by an informant history, provides information on severity that neither a cognitive assessment nor a functional assess-ment alone can provide. Two scales, the Clinicians Interview of Change,
(40) and the Clinical Dementia Rating,(41) have become 
widely used in this context.
Investigations
At the initial assessment, patients with dementia should be investi-gated for other disorders that could complicate, exacerbate, or be confused with AD. A dementia screen might include routine bio-chemistry, thyroid function tests, vitamin B
12 and folate estima-
tions, and a full blood count; many would also include syphilis serology, although the frequency of abnormal ﬁ  ndings is low. 
Neuroimaging is recommended in all cases by expert guidelines,
(42)

(42)
and serves two purposes—to exclude reversible causes of dementia and to contribute towards a deﬁ  nitive diagnosis. Thus using struc-
tural imaging with CT or, increasingly, with magnetic resonance imaging (MRI), the hippocampal atrophy of AD, the frontal pre-dominant atrophy of FTD and the lesions of vascular dementia can be identiﬁ  ed, adding to the speciﬁ  city of diagnosis. In practice, 
neuroimaging is often omitted particularly when patients present with a typical history of a slowly progressive dementia of many years standing. Functional scanning (single-photon emission CT (SPECT) in particular) can be useful where regional dementias are suspected, and MRI should be the imaging modality of ﬁ  rst choice

where vascular dementia is a possibility. An EEG is nearly always non-specifically abnormal even in the early stages of AD, in 
contrast with fronto-temporal degenerations where an EEG 
remains unaffected at a broadly equivalent severity. This can help to distinguish the conditions, particularly where there is neuroim-aging evidence of regional insufﬁ  ciency.
Aetiology and molecular neurobiology
Alzheimer’s disease is the most common dementia, affecting more 
than 20 per cent of the population over the age of 85 years. Epidemiological evidence has suggested risk factors and putative protective factors, but the greatest advances in understanding its pathogenesis have come from the combination of molecular and epidemiological approaches.
Neuropathology

At post-mortem, the brain in AD is lighter than aged-unaffected controls with more prominent sulci and a larger ventricular volume. Microscopic examination reveals the most prominent lesions described by Alzheimer—the extracellular plaque and intracellular neurofibrillary tangle. No consensus has developed regarding which of these lesions is responsible for the cognitive impairment 4.1.2 dementia: alzheimer’s disease

SECTION 4  clinical syndromes of adult psychiatry 338
of AD. Plaques, or more precisely amyloid load, might correlate 
with the degree of cognitive impairment,(43) although a signiﬁ  cant 
amyloid deposition is also found in normal, unimpaired, aged indi-viduals.
(30) However, there is a high degree of correlation between 
dementia severity and neurofibrillary tangle formation,(44)
although it is possible that some of the features of AD are more 
stable than others; for example, extracellular neuroﬁ  brillary tangles 
persist after the neurone has died, whereas extracellular Lewy bod-ies are not found.
The plaque consists of an amyloid core surrounded by dystrophic 
neurites, which are themselves ﬁ  lled with highly phosphorylated 
tau protein. Studies of Down syndrome brains have suggesteda temporal course to plaque formation. First, peptides derivedfrom the amyloid precursor protein ( APP ) are deposited in a
diffuse plaque.
(45) Over time this becomes organized as the

amyloid peptides become ﬁ  brillar and form the amyloid deposit, 
neuritic change then occurs, and the plaque becomes fullymature.
Neuroﬁ  brillary tangles are composed of paired helical ﬁ  laments, 
structures which are also found in the dystrophic neurites around mature plaques, and together with straight ﬁ  laments, in neuropil 
threads. These ﬁ  laments are themselves composed of the microtu-
bule-associated protein, tau, which is present in a stably and highly phosphorylated state.
(46,47)  Tau is a neuronal-speciﬁ  c protein,

(46,47)  Tau is a neuronal-speciﬁ  c protein, 
found predominantly in the axon that functions to stabilize microtubules, a property that is regulated by phosphorylation. Phosphorylated tau is less effective in promoting tubulin polymer-ization into microtubules; normal adult brain a proportion of tau is highly phosphorylated, but this proportion is considerably great-er in AD. Tau deposits are a feature of other disorders, such asprogressive supranuclear palsy and some fronto-temporal degen-erations
(48) and together these tau-related disorders have been 
grouped together as the ‘tauopathies’ . Mutations have been found in fronto-temporal degenerations with parkinsonism (FTDP-17), and in other tauopathies thereby emphasizing the importance of this molecule to neurodegeneration.
(49)
Braak and Braak(50) studied large numbers of brains from indivi-

(49)
duals who died at various ages and at different stages of dementia severity, which has resulted in the wide acceptance of the neuropa-thological staging of AD. The very earliest stages, before the clinical manifestation of dementia, are characterized by the appearance of highly phosphorylated tau in the hippocampus. In later stages, neuroﬁ  brillary tangles appear in the same brain regions and then 
become more widely distributed.
(a) The cholinergic hypothesis
The pathological changes in AD are localized both structurally and functionally. Plaques and tangles ﬁ  rst occur in the hippocampus 
before spreading to involve other regions. Some areas of the brain are relatively preserved—the occipital lobe is affected relatively late and the cerebellum appears to be spared from neuritic change (neuroﬁ  brillary tangles and the fully matured plaques, although

diffuse amyloid deposits do occur). Functional localization was demonstrated by evidence of the relatively greater and earlier loss of cholinergic neurotransmission. At post-mortem there is evi-dence of signiﬁ  cantly greater neuronal loss in the cholinergic 
nucleus basalis of Meynert and loss of cholinergic markers.
(51)
These observations led to the cholinergic hypothesis, which stated that the cognitive impairment of AD was due to a disorderpredominantly affecting cholinergic neurones. It was this hypoth-
esis that led to the development of pharmacological strategies to rectify cholinergic loss and the introduction of the ﬁ  rst compounds 
speciﬁ  cally designed for and efﬁ  cacious in AD. However, the cho-
linergic hypothesis was something of a simpliﬁ  cation as other neu-
rotransmitter systems (e.g. serotonergic and noradrenergic) are also affected in AD.
(b) The amyloid cascade hypothesis

In 1984, the protein deposited in blood vessels (congophilic angi-opathy) in AD was shown to be a 4-kDa peptide known as β-amy-
loid. This peptide, which is identical to the amyloid in plaques, is derived from a larger peptide, APP , the gene for which is coded on chromosome 21. Subsequently, mutations in the APP  gene were 
found in a family with autosomal dominant early onset AD. These two discoveries—the identiﬁ  cation of β-amyloid and the discovery 
of mutations in the parent APP  gene—led the way to the amyloid 
cascade hypothesis, which has remained the dominant molecular model of the disorder (reviewed in Refs
(52–54)). Many subsequent 
molecular observations have been consistent with this model, which posits the formation of β-amyloid as the initiating, or at

molecular observations have been consistent with this model, which posits the formation of β-amyloid as the initiating, or at 
least early event, leading to all the other changes observed includ-ing tau aggregation and phosphorylation, neuronal loss, choliner-gic deﬁ  cits, and clinical symptoms. Perhaps the most convincing 
evidence that there is such a unidirectional cascade comes from the observation that mutations in the APP  gene give rise to plaque for-
mation and also to neuroﬁ  brillary tangle pathology, whereas muta-
tions in the tau gene give rise to tangle formation but not to plaque formation in the tauopathies.
Much subsequent research has concentrated upon understand-
ing the metabolism of APP and the formation of β-amyloid peptide. 
APP is a ubiquitous single-pass cell-membrane protein expressed in many cell lines with a high degree of evolutionary conservation. 
At least three putative secretases cleave APP
(55) and the metabolic

(55) and the metabolic 
products can be detected in individuals unaffected by AD; the pro-cessing is not pathological in AD, but the balance between different metabolic routes may be shifted in the disease state. α-Secretase cleaves APP at the outer cell-membrane surface at a 
site within the β;-amyloid moiety itself. Clearly, α-secretase cannot 
therefore yield intact β-amyloid, and this metabolic route, resulting 
in a secreted product, APPs, and other fragments, is termed non-amyloidogenic. On the other hand, amyloidogenic metabolism is the result of β-secretase (also known as Beta Amyloid Cleaving 
Enzyme or BACE) cleaving APP beyond the amino terminus of β-amyloid and of γ-secretase cleaving the resulting peptides at the 
carboxy terminus in the cell. The β-amyloid products vary in 
length, with predominant species having a length of 40 or 42 amino 
acids. The longer peptides are somewhat more prone to forming

acids. The longer peptides are somewhat more prone to forming 
aggregates in vitro  and it is probable that a relative increase in the 
longer peptides is critical in pathogenesis, and that mutations in theAPP  gene increase these longer amyloid peptides. Transgenic 
mice overexpressing the mutated APP  gene also produce more 
β-amyloid peptide and have amyloid deposits in brain.
(56)
Interestingly, these animals do not develop other aspects of AD 
pathology, in particular they lack tangle formation. The nature of the toxicity of β-amyloid peptide is not fully understood but 
increasingly it appears that it is small aggregates (oligomers) that damage neurones rather than the longer ﬁ  brils that form the core 
of the plaque.
(57)

339
(c) The presenilin genes
Mutations in presenilin-1 (PS-1)  and presenilin-2 (PS-2) , two very 
similar genes on chromosome 14 and chromosome 1 respectively, also cause early onset autosomal dominant AD. The proteins encoded by these genes are part of the γ-secretase complex that 
metabolizes APP to β-amyloid. In fact these unique proteins turn 
out to have very many substrates and function in relation to many 
of these to release an intracellular component of a membrane bound protein that then translocates to the nucleus and triggers gene transcription events.
(58) This is certainly the case for APP and 
also for Notch protein, which is also implicated in some other neu-rodegenerative conditions, for example. Mutations in the presenilin genes result in an increase in the production of β-amyloid probably 
through interfering with the normal γ-secretase complex.
Tangle formation and tau phosphorylation
Tangles are composed of paired helical filaments, themselves

Tangles are composed of paired helical filaments, themselves 
composed of aggregated and highly phosphorylated tau.(59–62)
There are other post-translational modiﬁ  cations in tau, including 
truncation, and it is not fully determined which of these are pri-mary events. However, in post-mortem studies, neuropathological evidence does suggest that highly phosphorylated tau accumulates in the brain before the formation of tangles, and before the clinical manifestation of AD suggesting that it is a early change in the path-ological process.
(63)
Protein phosphorylation is a product of kinase and phosphatase 
activity. It is likely that many such enzymes may participate in the regulation of tau phosphorylation in the brain, but two have been shown to be predominant. In cells, and in vitro , glycogen synthase

kinase-3 and cyclin-dependent kinase 5 (CDK5) seem to be the predominant tau-kinases and protein phosphatase 2A is probably the predominant tau phosphatase.
(64,65)
Molecular genetics
Mutations in three genes have been found to cause early onset famil-ial AD, which is inherited in an autosomal dominant fashion.
(66,67)
Mutations in the APP gene (on chromosome 21) are the least com-
mon, only affecting perhaps 20 families worldwide. Mutations in PS-1  (on chromosome 14) are somewhat more frequent, although 
are still a rare cause of AD. Mutations in PS-2  (on chromosome 1)

are still a rare cause of AD. Mutations in PS-2  (on chromosome 1) 
appear to be largely restricted to an ethnic German people residing in the United States, suggesting an individual founder effect. Individuals with Down’s syndrome are at extremely high risk of AD, with neuropathological evidence being present in virtually all indi-viduals living to middle age, probably because of trisomy APP (on chromosome 21). Mutations in other genes gives rise to disorders showing similarities to AD and much has been learnt from these ﬁ ndings about the overlap between neurodegenerative disorders. 
These genes include tau and progranulin , mutations in which give 
rise to FTD and related disorders.
The genetic component of late-onset AD has been demonstrated 
by epidemiological studies, showing that a family history of dementia is the largest single risk factor for AD.

(68) However many, 
perhaps most, patients with AD do not have a positive family history, thus giving rise to the idea of ‘sporadic’ AD with a separate aetiology to ‘familial’ AD. For late-onset AD this concept is outmoded and redundant. Many patients with AD do not have a family history because of attrition of family members due to death by other causes. For the cohort currently suffering from AD their parents were born

in the latter part of the nineteenth century or early years of the twen-tieth, lived through two major world wars, and reached adulthood before the discovery of antibiotics. It is not surprising that few patients with late-onset AD have two parents and more than one sibling living to the age of onset of AD, and if one parent died young and there are no elderly siblings then the family history is non-infor-mative. Risk ﬁ  gures for relatives of probands with late-onset AD 
have been calculated and can be useful in c ounselling families.
(69)
One gene has been unequivocally associated with late-onset AD, 
although even this gene accounts for only something like 50 per cent of the genetic variance.
(70) The apolipoprotein E  gene ( APOE , gene; 
apoE, protein) on chromosome 19 has three common alleles, coding for three protein isoforms that differ by the substitution of an amino acid at just two positions. Of the three alleles ε3 is the

apoE, protein) on chromosome 19 has three common alleles, coding for three protein isoforms that differ by the substitution of an amino acid at just two positions. Of the three alleles ε3 is the 
most frequent and ε2 the least; following linkage to chromosome 
18 it was demonstrated that the ε4 allele confers risk, whilst the ε2
may be protective.
(71,72)
The mechanism of action of the APOE  gene in increasing the 
risk of AD is not known. As APOE  variation is a major genetic 
inﬂ uence on serum cholesterol (people with the APOE ε4/* geno-
type have higher serum cholesterol levels), it is possible that an altered lipid metabolism—either peripherally or locally—might affect the pathogenesis of AD.
(73,74)  Alternative theories arise from 
in vitro  studies, which show a differential binding of APOE protein 
isoforms both to amyloid protein and to tau protein.
Other genes have been associated with AD, but none have been

Other genes have been associated with AD, but none have been 
replicated in as many studies as APOE . It is likely that a combina-
tion of linkage and association studies using large populations will identify the other genes that inﬂ  uence AD, either alone or in inter-
actions with other genes or the environment.
Treatment
For many conditions the goals of treatment or intervention are self-evident—cure, prevention of relapse, and resolution of symptoms. For AD, however, the goals of treatment can be less obvious and dif-fer between patients and for individual patients over time. Ultimately, the quality of life of the patient should be improved, but assessing quality of life is difﬁ  cult in those with dementia, and given the early 
loss of insight who is to judge such issues?
(75) Quality of life may

(75) Quality of life may 
appear poor—patients may have diminished emotional repertoires, few pleasurable activities, and considerable handicap—but they may share none of the negative cognitions experienced by others with a similarly questionable quality of life induced by differentillnesses. Other patients may appear content or happy, despite the loss of the autonomy and self-awareness normally considered an essential component of a good quality life. The needs of the patient can be difﬁ  cult to ascertain.
(76) Equally, the treatment unit in AD 
includes carers, and there are times when the patient’s quality of life is in conﬂ  ict with the quality of life for other members of the
family.
(77) Resolving such conﬂ  icts of interest and other moral and 
ethical issues is part of the treatment process in AD. With the arrival of speciﬁ  c treatments for AD and the prospect of disease-modifying

ethical issues is part of the treatment process in AD. With the arrival of speciﬁ  c treatments for AD and the prospect of disease-modifying 
therapies, an even harder question arises regarding prolonging life for those with dementia: if quality of life appears poor to observers, is it right to prolong the process, can quality of life in those with dementia truly be assessed, or should carers and families be allowed to assess for themselves the beneﬁ  ts and costs of treatment?4.1.2 dementia: alzheimer’s disease

SECTION 4  clinical syndromes of adult psychiatry 340
There is no single model of management of patients with AD. 
In many countries management is the role of the gerontologist 
or neurologist. In others, as in the United Kingdom, the old-age psychiatry team provides the core specialist services. Many, perhaps even the majority, of those with AD are managed within primary care with the support of social services. Referral from primary care to specialist services will be according to local agreements, but most would concur that behavioural disturbance or the use of speciﬁ  c 
drugs to treat AD warrant referral to secondary care. Interventions for AD, whether provided in primary or secondary care, can be thought of as directed towards the patient, the patient’s family, and the patient’s environment. Guidelines on the identiﬁ  cation and 
management of patients with dementia have been produced and may be a constructive approach to ensuring best clinical practice.
(78)
Managing the patient

(78)
Management of the patient with dementia is discussed in greater detail in Chapter 4.1.13. Management starts with the assessment and diagnosis, and perhaps the difﬁ  cult dilemma is how much of 
the diagnosis and prognosis to discuss with the patient.
(79–81)  Most 
practitioners do not discuss the diagnosis with the patient them-selves, although practice is changing and especially in the early stages a frank consultation can be beneﬁ  cial.
A large part of managing the patient is directed towards manag-

ing mood and behavioural disturbance. Accurate assessment of the disturbance is critical, and includes determining the antecedents and responses to the behaviour as well as a full description of the behaviour and any associated abnormalities in the mental state. Treatments of behavioural disturbance in AD are most often behavioural and sometimes restricted to giving information to carers. Evidence overwhelmingly suggests that anti-psychotic med-ication is relatively ineffective and has frequent adverse effects in dementia.
(82,83) They should be a treatment of last resort, if at all.
Speciﬁ  c treatments for AD have been developed, concentrating 
in clinical trials on ameliorating the core symptom of cognitive impairment. The ﬁ  rst to be licensed were the cholinesterase inhibi-
tors followed by memantine. Drug treatments for AD are described in Chapter 6.2.7.
Managing the family

Although patients may not appreciate or be able to follow a detailed discussion of the diagnosis and prognosis, their relatives, spouses, and other carers will. This is an important part of the treatment process; as the carer provides the main interventions for much of the period of the disease process, care should be taken to ensure that appropriate and sufﬁ  ciently complete information is given.
Caring for a patient with AD can be difﬁ  cult and stressful and 
some carers suffer accordingly and need, and may beneﬁ  t from 
support.
(84) The characteristics of both carers and patients inﬂ  uence 
the impact that this ‘burden’ of caring has on the carers themselves. Men in general, and husbands in particular, seem to be less vulner-able to the adverse effects of caring, possibly because of the response seen in many male carers of rapidly and effectively recruiting out-side help.

(85) Women may be socialized into accepting more caring 
roles themselves and therefore seek less help. Non-white carers appear to suffer from less adverse consequences of caring, perhaps because of cultural differences in the perception of family bonds.
(86)
Patient characteristics that increase the burden of caring include behavioural disturbances,(25) depression, and unawareness of 
cognitive impairment but not the cognitive impairment itself. 
Although the core outcome variable in clinical trials of AD drugs is the severity of cognitive impairment, it is not the variable that induces most stress in relatives nor is it the variable that predicts entry to residential care. Other variables are almost certainly pro-tective, and caring for a loved one with dementia is not a univer-sally negative experience. Much caring is done willingly, effectively, with love, and without complaint.
Carer support groups offer much to a person with a relative afﬂ  ict-

ed by AD. Through support groups, and especially through the national AD societies and the umbrella group—AD International—carers can obtain up-to-date and useful information regarding all aspects of AD. A support group can help individuals practically and emotionally through difﬁ  cult times. Many carers talk of the support 
group as a lifeline, although little empirical evidence exists as to the impact on carer well being.
One particular intervention for the family is that of genetic

One particular intervention for the family is that of genetic 
counselling. Many relatives are worried about inheriting AD. This concern might arise from two sources—the frequent discussion of genes ‘for’ AD in the media and the observation of familial occur-rence of AD in many individual families. For families with clinically apparent familial AD, advice, information, and where appropriate, genetic testing can be arranged through a genetics centre. Where predictive testing is contemplated for genes causing autosomal dominant, early onset AD this will adhere to guidelines established for Huntington’s disease. Genetic testing in late-onset AD is not recommended at the present time but is the subject of an ongoing 
research programme.
(87)
Managing the environment
The mainstay of interventions for AD are provided by social services.

(87)
The mainstay of interventions for AD are provided by social services. 
The goal of the provision of social care in people with AD is to provide an environment that is comfortable, stimulating, and, above all, safe. For most patients, and for all patients in the early stages, this means care at home, perhaps with the support of home-meal delivery and home-helps to provide shopping and cleaning assistance. Further home care may become necessary as the patient requires assistance with basic self-care tasks such as washing and dressing. The carer may require a sitting service, either for periods during the day to allow them time to themselves or in the evening to allow them to attend a carers group or for socializing. Safety issues are especially important for those with dementia living alone. There are inherent risks to the patient themselves if they wander out of the home and risks to others if the gas can be left on or ﬁ  res 
started.

started.
Day care is appropriate for many patients, ideally in a specialist 
unit. In a generic facility for elderly people those with early dementia can receive little input and those with moderate or advanced dementia can necessitate too much input from the day-centre staff. A good dementia specialist day-care facility will provide the staff-ing ratio appropriate to patients with a range of 70s, in addition to providing a varied programme of group and recreational facilities to maintain interest and stimulation. Day centres, where patients are arrayed around the edge of the room with a television as a focal point, are, or should be, consigned to history. Day care provides essential respite to many carers, and longer periods of occasional or regular respite can prolong the period a patient can remain in their own home.

341
The multidisciplinary team consisting of care workers, social ser-
vices, community psychiatric nurse occupational therapist, and 
psychologist can maintain patients at home more effectively and for longer periods than can clinicians alone. However, long-term care becomes a necessity for many patients at some point. The costs of providing nursing-home care are huge and far outweigh the costs of providing relatively intensive community care or relatively costly drugs. If treatments were shown to reduce the total length of stay in nursing homes then this would affect the cost–beneﬁ  t ratio 
of these compounds considerably.
Translational research in AD

The rapid and comprehensive advances in understanding the molecular basis of AD has led to the promise of advances in health care—translational or bench to bedside research. Most importantly are potential disease modifying therapies. These are distinguished from symptomatic therapies in that they are designed to halt or slow down the disease process itself. Designing trials to assess efﬁ  -
cacy of a potential treatment that might only slow down deteriora-tion, and differentiating symptomatic effects from disease-modifying effects is not easy.
(88) Two broad approaches are

(88) Two broad approaches are 
suggested—either a comparison of slopes of decline in which case a disease-modifying therapy would result in divergent slopes whereas a symptomatic therapy would result in parallel slopes, or strategies such as delayed start where in the case of a disease-modi-fying therapy the treatment arm of the delayed group never do quite as well as the early start group.
(89)
Many approaches to disease modiﬁ  cation are being pursued 
including therapeutics designed to alter APP processing—BACE inhibitors and γ-secretase inhibitors for example—or therapeutics 
designed to prevent β-amyloid from aggregating or for increasing 
the clearance of β-amyloid.
(90) Many such compounds are in early

(90) Many such compounds are in early 
stages of development and some were in phase III trials in 2007. Other potential therapies attempt to reduce tau phosphorylation or aggregation and yet other approaches are predicated onepidemiological ﬁ  ndings such as the observation that non-steroi-
dal anti-inﬂ  ammatory drugs reduce risk of AD or that diabetes 
increases risk. Primary preventative therapies are probably even further away than disease-modiﬁ  cation therapies but modifying 
cardiovascular risk or other approaches have been suggested. Secondary prevention, possibly in those with memory impairments not amounting to dementia (minimal cognitive impairment), isa more realistic prospect rendering the determination of thevery earliest signs of disease or evidence of a prodromal state ahigh priority.
A second signiﬁ  cant translational target in AD research close to

A second signiﬁ  cant translational target in AD research close to 
clinical utility is that of biomarkers.
(91,92) A marker is sought that 
might help in diagnosis, prediction or disease monitoring. For diagnosis a biomarker is sought that would make early or differential diagnosis more accurate, for prediction a biomarker that would help in predicting which elderly people were more likely to suffer from dementia or, more likely, which of those with mild cognitive impairment are more likely to convert to dementia. A marker of disease progression is sought that could supplement clinical assess-ments of deterioration. Of the many approaches to biomarkers, biochemical assays of tau and β-amyloid in CSF
(91,93) and serial 
quantitative MRI(94) are the most promising although markers in 
plasma appear promising.(95,96)Conclusions
For the foreseeable future, AD will remain a disorder afﬂ  icting a

For the foreseeable future, AD will remain a disorder afﬂ  icting a 
large proportion of the world’s elderly. The impact on developing countries especially will be considerable. Care for these patients will continue to be provided from many sources, with specialist services being necessary to compliment primary and generic services, particularly for those patients exhibiting the complex psychiatric phenomenology described by Alzheimer and for those patients where speciﬁ  c drugs are indicated. As the molecular patho-
genesis of AD is increasingly understood it is to be hoped that this is translated into treatments ever more effective in modifying or preventing the disease process itself.
http://www.alzforum.org/
http://www.alzheimers.org.uk/http://alzheimers-research.orghttp://www.alz.org/

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SECTION 4  clinical syndromes of adult psychiatry 344
4.1.3 Frontotemporal dementias
Nosological classiﬁ  cation of organic dementia is based on current 
knowledge and theories of aetiology, including genetics, clinical picture, the pathological substrate, and the predominant location of brain damage. This chapter is concerned with dementiasyndromes caused by a degenerative disease primarily affectingthe frontal and temporal lobes, named frontal-lobe dementia
(1)
or frontotemporal dementia ( FTD ).(2) The terminology should
be viewed from a historical perspective. The relationship between localized cortical atrophy in dementia and symptoms of aphasia was ﬁ  rst reported by Pick in 1892.
(3) The pathological account of 
this lobar degeneration by Alzheimer in 1911 described ‘ballooned’ neurones (Pick cells) and argentophilic globes (Pick bodies),
(4) and 
the clinicopathological entity was named Pick’s disease .

(4) and 
In the 1980s, attention was drawn to a larger group of
frontal-lobe dementias associated with frontotemporal cortical degeneration.
(5–7)  The Lund–Manchester consensus of 1994
delineated the prototypical clinical syndrome of FTD with three neuropathological constituents, frontal lobe degeneration ofnon-Alzheimer type ( FLD ),
(5) (alternatively designated ‘ dementia 
lacking distinctive histology ’),(8) Pick’s disease, and motor
neurone disease ( MND ) with dementia ( FTD-MND ).(2) The 1998 
consensus on clinical diagnostic criteria for frontotemporallobar degeneration ( FTLD )
(9) encompassed two additional demen-
tia syndromes; progressive non-ﬂ  uent aphasia ( PA),(10,11) and 
semantic dementia .(12) Corticobasal degeneration ( CBD ) and

semantic dementia .(12) Corticobasal degeneration ( CBD ) and 
progressive supranuclear palsy ( PSP) have also been associated 
with FTLD.(13) A changing clinical classification is shown in
Fig. 4.1.3.1. The addition of important genetic and histochemical characteristics has further added to the complex classiﬁ  cation of 
FTD and FTLD with a risk of developing numerous and partly competing deﬁ  nitions. FTLD may be further subclassiﬁ  ed into 
forms positive or negative for tau and ubiquitin. The ubiquitinated form will be referred to as FTD-U , which is synonymous to
FL TD-U .
(14)
On a neuropathological basis about two-thirds of the FTLD cases 
are of the type with ubiquitinated inclusions (FTD-U) or of FTD type without such inclusions (FLD), both lacking tau pathology.
(14,15)

(14,15)
In an attempt to classify FTD forms from a structural point of view, FLD might be appointed as a basic form, showing type and distri-bution of main pathological changes common to the majority of FTLD forms. T o this set of alterations are added further features 
proceeding in the description of frontotemporal degenerative 
disorders (Table 4.1.3.1).
In FLD, the cortex is the site of a simple  degenerative process 
resulting in a cortical atrophy which is frontotemporal with or with-out asymmetries, moderate or even at times mild. It involves corti-cal layers 1–3, showing neuronal loss, gliosis, and microvacuolation, seen also in the striatum in a small proportion of cases as well as a mild-to-moderate degeneration of the substantia nigra.
(5) DLDH

(5) DLDH 
has essentially the same pathology as FLD.(8)In FTD-U the ubiquitin-positive inclusions and dystrophic neu-
rites supplement the picture of FLD, as also described in FTD, linked to chromosome 3.
(16) The inclusions contain a ubiquitinat-
ed protein, also identiﬁ  ed in some other varieties of FTD such as 
FTD-MND.(17) Here there is also a degeneration of motor neu-
rones and paths. The language variants of FTLD show a mainly temporal degeneration in semantic dementia and an asymmetric frontotemporal degeneration with left-sided predominance in PA.
With a mainly frontal or frontotemporal including anterior cin-

gulate gyrus involvement FTD differs markedly from Alzheimer’s disease (AD) with its posterior temporal parietal, posterior cingu-late, and severe hippocampal involvement and also with Lewy bodies, amyloid, and plaque pathology not seen in FTD. So far mentioned FTD forms belong in the same histopathological group of non-tauopathies and further share a frequent and individually varyingly severe white-matter sclerosis, which is often predomi-nantly frontal and may be primary or secondary.
(18) It is also seen 
in the tauopathy group and in forms of vascular dementia.
The remaining, less common forms comprise the FTD-tau

The remaining, less common forms comprise the FTD-tau 
group. In Pick’s disease the degenerative process is more intense and partly involves all cortical layers, creating a severe circum-scribed or lobar frontotemporal atrophy referred to as ‘knife blade atrophy’ . Microscopically there are tau-positive neuronal inclusions and sometimes glial tangles and often ballooned nerve cells. The FTD with Parkinsonism (FTDP-17) group with a number of famil-ial disorders shares basic pathological features with the FLD but is Fig. 4.1.3.1 Clinical classiﬁ  cation of frontotemporal dementias.FTLDFTD
Progressive non-fluent aphasia
Semantic dementia
CBD, PSP, and othersFLD type
Pick type
MND typeClinical criteriaClinical/pathological criteria
Lund/Manchester 1994(2)
Neary et al 1998(9)
Table 4.1.3.1  Organic dementia with frontotemporal lobar 
degeneration (FTLD)

Pick type
Frontal lobe degeneration of non-Alzheimer type (FLD) (Dementia lacking 
distinctive histology) without ubiquitinated inclusions
FTD with ubiquitin-positive inclusions (FTD-U)
Familial FTD with chromosome 3 mutation (FTD-3)
FTD with motor neurone disease (FTD-MND)
Progressive non-ﬂ  uent aphasia (PA)Semantic dementia Pick’s diseaseFTD with Parkinsonism (FTDP-17)Corticobasal degeneration (CBD)Progressive supranuclear palsy (PSP)

345
regularly more severe in the basal ganglia and substantia nigra.(19)
Glial cells and neurones contain various types of tau-positive inclu-
sions. CBD is structurally and clinically heterogeneous, resulting in overlap with other diseases, especially PSP .
(20) These two may rep-
resent varieties of the same pathological process, less obviously belonging in the FTD group even if a similar laminar frontal cortical degeneration and related symptoms are part of the presen-tation. In CBD ballooned neurones, tau-positive inclusions in neuronal and glial cells, white-matter rarefaction and nigral degen-eration may be found. For PSP different forms and patterns are noted but it basically affects more widely the striatum, basal gan-glia, and hypothalamus. It also involves the brain stem including the substantia nigra as well as the cerebellum, again with silver- or tau-positive inclusions and tangles in neurones and glial cells.
(21)
Epidemiology

(21)
Most demographic data concern the grouping of FTD, not separat-ing FLD and Pick’s disease. Pick’s disease is rare, estimated at 24–60/100 000 in Minnesota and 30–60 in Switzerland.
(22) The cal-
culated prevalence of FTD in the Netherlands is 10.7 per million between 50 and 60 years of age and 28 between 60 and 70 years.
(23)
The prevalence of FTD in the province Zuid-Holland in the Netherlands was 3.6/100 000 at age 50–59, 9.4 at age 60–69 years, and 3.8 at age 70–79 years.
(24) Pasquier et al.(25) diagnosed FTD in 
4.8 per cent of all types of dementia. The marked geographic varia-tion of the prevalence might be due to genetic and environmental factors, but also inﬂ  uenced by differences in the diagnostic process 
and the age group studied. In a clinical study of a total catchments area of 20 million people in Germany the relative proportion of FTLD was 1.9 per cent.
(26) The prevalence of dementia in motor

(26) The prevalence of dementia in motor 
neurone disease has been estimated to 2–6 per cent.(27) The propor-
tion of FTD in relation to all types of dementia in different clinico-pathological studies varies between 5 and 18.9 per cent.
(7, 8, 28–30)
The ﬁ  rst clinical manifestations of FTD usually appear in the 
presenium, in some cases as early as 35 and seldom after 70 years of age. The mean age at onset in post-mortem veriﬁ  ed FLD cases is 
56 ± 7.6 years with a mean duration of 8 ± 3.4 years (range 3–17 years).
(31) The mean age of onset in Pick’s disease is similar, 
62 years, with a range of 40–80 years and a mean survival of 9.8 years with a range of 4.8–21.2 years.
(22) The large variations of

(22) The large variations of 
the duration of FLD and Pick’s disease are similar to that of early-onset AD. The clinical onset of MND dementia is usually in the sixth decade and the mean duration is about 30 months. Age at onset is similar in familial and sporadic cases of FTD and sometimes past 80 years.
(32) The Lund–Manchester consensus on 
clinical criteria for FTD is summarized in Table 4.1.3.2.
Disordered behaviour
The early stage of FLD and Pick’s disease is characterized by changes of personality and behaviour, affective symptoms, and a progressive reduction of expressive speech. The clinical onset is insidious with slow progression without ictal events. The changes of personality and behaviour are rather non-speciﬁ  c and easily

misinterpreted as a non-organic mental disease such as mood dis-order, stress reaction, schizophrenia, or other psychotic reaction. Loss of insight concerning the mental changes is an early and alarming manifestation of the disease. FTD patients may, however, 
consult a doctor referring to symptoms such as anxiety, tiredness, and strange somatic complaints combined with bizarre hypo-chondriacal ideas.
The early loss of personal and social awareness is seen as neglect 
of personal hygiene and grooming, and tactlessness and antisocial behaviour.
(6, 9) The impaired control of behaviour is seen as 
increased sentimentality, inadequate smiling, inappropriate joking, irritability, and acts of aggressiveness, leading to conﬂ  icts at home

increased sentimentality, inadequate smiling, inappropriate joking, irritability, and acts of aggressiveness, leading to conﬂ  icts at home 
and work. Craving for affection and sexual contact may be easily provoked, but usually expressions of sexual disinhibition are possible to divert. Impulse buying, shoplifting, indecency, and other disinhibited behaviour may, however, lead to rejection by the family and society. Such unpredictable and pseudopsychopathic Table 4.1.3.2  The Lund–Manchester consensus (1994) on clinical 
criteria for frontotemporal dementia (slightly modiﬁ  ed)
(2)
Core diagnostic features
Behavioural disorder Insidious onset and slow progression Early loss of insight into changes of own mental state
 Early loss of personal and social awareness

(2)
 Early signs of disinhibition and lack of judgement Mental rigidity and inﬂ  exibility Stereotyped, repetitive, and imitating behaviour Hyperorality, oral/dietary changes Utilization behaviour Distractibility, impulsivity, and impersistence
Affective symptoms
 Depression, anxiety, excessive sentimentality
 Hypochondriasis, bizarre somatic complaints
 Emotional bluntness, apathy, and lack of empathy Amimia
Speech disorder
 Progressive reduction of speech output Stereotypy of speech, perseveration Echolalia Late mutism
Spatial orientation, receptive speech, and praxis preserved
Physical signs
 Early primitive reﬂ  exes
 Early incontinence Late akinesia, rigidity, and tremor Low and labile blood pressure

 Normal EEG despite clinically evident dementia Brain imaging (structural and/or functional): predominant frontal and/or 
anterior temporal abnormality
 Neuropsychology: profound failure on ‘frontal-lobe’ tests in the absence of 
severe amnesia, or perceptual spatial disorder
Supportive diagnostic features
 Onset before 65 Positive family history of similar disorder in a ﬁ  rst-degree relative Bulbar palsy, muscular weakness and wasting, fasciculations (motor 
neurone disease)
(Reproduced from A. Brun, E. Englund, L. Gustafson, et al. Consensus statement—
clinical and neuropathological criteria for frontotemporal dementia, Journal of Neurology, 
Neurosurgery, and Psychiatry , 57, 416–18, copyright 1994, BMJ Publishing Group Ltd.)4.1.3 frontotemporal dementias

SECTION 4  clinical syndromes of adult psychiatry 346
behaviour imposes severe strain on the patient’s family, leading in 
some cases to economic problems, divorce, and even suicide in the family.
(33) Complications of this type are uncommon in families 
with an AD patient. FTD patients tend to become inattentive and careless and a danger to trafﬁ  c. Changes in drinking behaviour are 
sometimes reported. The patient starts to drink more frequently and in larger quantities than before. The changes of behaviour, which may lead to misdiagnosis of alcohol-induced dementia, can often be controlled by a ﬁ  rm attitude from relatives.
The FTD patient becomes emotionally shallow and blunt, showing 
less concern about family and friends. The patient is described as egocentric, rigid, and lacking empathy. The early emotional changes may be difﬁ  cult to differentiate from non-organic personality

less concern about family and friends. The patient is described as egocentric, rigid, and lacking empathy. The early emotional changes may be difﬁ  cult to differentiate from non-organic personality 
disorders and affective disorder. Mood changes towards euphoria, especially when associated with press of speech and overactivity, may at ﬁ  rst be mistaken for a hypomanic or manic state. Slowly 
developing apathy, in combination with sparse mimical movements and verbal aspontaneity, may be misdiagnosed as depression. During the depressive reactions, which are mostly of short dura-tion, the patient may become dysphoric, and dwell on suicidal thoughts. FTD patients are often diagnosed as depressed and treated with antidepressant medication during the early stage of the disease.
(32)
Early symptoms of dementia must be judged against information

(32)
Early symptoms of dementia must be judged against information 
about the patient’s premorbid personality, education, and social background. The vast majority of cases show normal premorbid personality although a few have previously manifested anxiety and restlessness. The emotional features in FTD do not seem primarily related to premorbid personality traits but rather to the distribution of brain pathology as shown at autopsy and brain imaging.
(34)
Other symptoms
A striking feature of FTD is the stereotyped and perseverative 
behaviour  seen as wandering, clapping, humming, dancing, and 
hoarding of objects, as well as complex rituals involving washing and dressing. Such behaviour sometimes reaches psychotic inten-sity. Imitative behaviour is frequent in FTD and occurs more often than in AD.
Hallucinations and delusions  are reported in about 20 per cent

Hallucinations and delusions  are reported in about 20 per cent 
of FTD and early-onset AD cases. The psychotic symptoms in FTD are often bizarre and the combination with emotional changes and stereotypy of speech and behaviour gives the impression of functional psychosis with schizophrenia as an early tentative diagnosis.
(6–8) The psychotic symptoms in early-onset AD seem 
more strongly related to the cognitive failure with memory failure, impaired recognition, and disorientation, and the degeneration of the temporoparietal association cortex.
(6)
The human counterpart of the Klüver–Bucy syndrome  has 
been reported in FLD and in Pick’s disease. The hyperorality and 
changes of oral/dietary behaviour are seen as overeating, food 
fads, excessive smoking, and alcohol consumption. Utilization behaviour, deﬁ  ned as an irresistible impulse to explore and use

fads, excessive smoking, and alcohol consumption. Utilization behaviour, deﬁ  ned as an irresistible impulse to explore and use 
objects in the visual environmental, shows important similarity to the hypermetamorphosis and distractibility of the Klüver–Bucy syndrome.
(35) The Klüver–Bucy syndrome in AD is usually less complete than in FTD with less hypersexuality and utilization 
behaviour, supporting the suggestion that frontal as well as tempo-ral limbic involvement is needed to produce the syndrome in 
humans.
(6)
Dissolution of language
A core feature of FTLD is progressive impairment of speech and language. In FTD, this has been described as dissolution du langage
orSprachverödung .
(6) Speech becomes aspontaneous with word-
ﬁ nding difﬁ  culties and frequent use of stereotyped comments and

ﬁ nding difﬁ  culties and frequent use of stereotyped comments and 
set phrases. During the early stage there may also be increased pres-sure of speech. The language dysfunction in FTD is dominated by dynamic expressive failure, which is in agreement with damage in the frontal cortex especially premotor areas. Echolalia is observed in about 50 per cent of FTD and Pick cases.
(31) Finally the patients become 
mute which in combination with the amimia makes communication extremely difﬁ  cult. The ability to understand information and instruc-

tions usually remains until comparatively late in the course of FTD, as does the ability to write. The handwriting may, however, change in magnitude, spelling, and speed of writing. These disturbances are unlike the temporoparietal type of dysgraphia and global dysphasia observed in AD. The symptom constellation of palilalia (stereotypy of speech), echolalia, mutism, and amimia (PEMA syndrome of Guiraud) is typical of FTD and seldom found in AD.
There are important similarities between the speech disorder 
of early FTD and the clinical spectrum of PA,
(10) characterized by

(10) characterized by 
effortful speech production in the context of preserved word comprehension and relative preservation of memory and practical abilities. Dementia often develops later in the course, and the underlying degenerative process may be similar to that of FLD, with a predominant and early involvement of the speech-dominant hemisphere. Semantic dementia, the ﬂ  uent language variant of 
FTLD is characterized by progressive loss of word retrieval and understanding, and recognition of sensory stimuli.
(36) The 
pathological substrate is bilateral, often asymmetric temporal lobe degeneration.
Few pathological somatic ﬁ  ndings including neurological symptom 
are reported early in FTD. However, primitive reﬂ  exes may appear

are reported early in FTD. However, primitive reﬂ  exes may appear 
early, while akinesia, rigidity, and tremor may emerge later in the course. Increased muscular tension is, however, signiﬁ  cantly more 
common in AD.
(6) The spectrum of FTLD also includes the syn-
drome of the disinhibition–dementia–parkinsonism–amyotrophy complex linked to chromosome 17 also named FTD-17.
(37)
Generalized epileptic seizures may appear in FTD although less 
prevalent than in AD, and myoclonic twitchings and logoclonia which are prevalent in early-onset Alzheimer’s cases are rare in FTD. Urinary incontinence, which is reported early in about 50 per cent of FTD cases, is a comparatively late feature in uncomplicated early-onset AD.
FTD patients in general have low and labile blood pressure with

FTD patients in general have low and labile blood pressure with 
a high prevalence (50 per cent) of orthostatic blood pressure drops and syncopal attacks. These symptoms are, however, also reported in early-onset AD (40 per cent) and late in the course of vascular dementia (50 per cent). The relationship between blood pressure changes and brain damage especially the white-matter changes in FTD is still unclear.
(18)

347
Dementia in motor neurone disease
The clinical picture of the dementia in motor neurone disease is 
similar to that in FLD with early changes of personality and behav-iour, emotional changes such as euphoria and apathy, and signs of disinhibition and hyperorality.
(38) Speech becomes stereotyped 
and perseverative, later developing into mutism. Receptive speech function, orientation, and practicable abilities remain relatively untouched by the degenerative process. The mental changes may appear early and even precede development of typical neurological features.
EEG
The EEG may be normal or only slightly pathological in FTD at a stage when dementia is strongly suspected or clinically evident, but it is usually pathological late in the course. This has been shown in FLD, Pick’s disease, and FTD-MND.
(39) By contrast, EEG is almost

(39) By contrast, EEG is almost 
always pathological in AD even at an early stage. Quantitative EEG mapping and repeated recordings may strongly improve the differential diagnosis between FTD and AD.
(32)
Brain imaging and other investigations
Structural and functional brain imaging has strongly improved the diagnosis and differential diagnosis of FTD, AD, and other dementias. Cortical atrophy with more or less frontal focal accen-tuation, sometimes asymmetrical, is shown with CT and magnetic resonance imaging ( MRI ).
(8,40) MRI may show signiﬁ  cantly more 
prevalent and severe frontal periventricular white-matter lesions in FTD patients than in matched normal controls. The anterior–posterior gradient of the atrophic changes may, however, contrib-ute to the differentiation from AD.
(18,40)  The differential diagnosis 
from vascular dementia with frontal subcortical lesions, but lack-ing large cortical infarctions, may be difﬁ  cult.

Functional brain imaging measuring regional cerebral blood 
ﬂ ow (rCBF) and metabolism with SPECT, PET, and other tech-
niques show frontal and frontotemporal ﬂ  ow pathology in FTD 
with better preserved perfusion in posterior areas.
(41,42) PET stud-
ies have indicated the ventromedial frontal cortex as the earliest site of imaging pathology.
(43) These changes may at an early stage 
be mild and asymmetric in accordance with the clinical picture.
Recently several biomarkers in the cerebrospinal ﬂ  uid (CSF) 
have been developed for differential diagnosis of dementia. Riemenschneider et al .
(44) reported signiﬁ  cantly higher CSF tau 
concentrations in FTD compared to healthy controls, but signiﬁ  -
cantly lower than in AD, while CSF Abeta42 levels were signiﬁ  cantly

cantly lower than in AD, while CSF Abeta42 levels were signiﬁ  cantly 
lower in FTD than in controls, but signiﬁ  cantly higher than in AD. 
Early diagnosis of FTD might in the future be based on a combina-tion of proﬁ  le and levels of CSF biomarkers such as tau, β-amyloid, 
and neurofilaments.
(45) Interestingly tau levels are dependent 
on lobar localization but independent of the degree of cerebral atrophy.
(44,46)
Assessment of cognitive impairment
The cognitive changes, which appear early in FTD, may be difﬁ  cult 
to evaluate due to the patient’s emotional and behavioural changes. 
Distractibility and slightly reduced recent memory are common 
ﬁ ndings and remote memory is also impaired although to a lesser extent than in AD. The patients show signiﬁ  cant impairment on

ﬁ ndings and remote memory is also impaired although to a lesser extent than in AD. The patients show signiﬁ  cant impairment on 
‘frontal-lobe’ tests such as the Wisconsin card sorting test, word ﬂ uency test, and the Stroop and trail-making tests. The early test 
proﬁ le is characterized by slow verbal production and relatively 
intact visuospatial ability, reasoning, and memory, while intellec-tual and motor speed are reduced.
(10,47) Early AD usually shows 
a relatively preserved verbal ability and simultaneous impairment of reasoning ability, verbal and spatial memory dysfunction, dysphasia, and dyspraxia.
(10,48,49) Difﬁ  culties in understanding 
instructions are found early only in a minority of FTD cases. Misspelling and dyscalculia are sometimes reported early in FTD.
Discrimination between FTD and AD can be based on a short

Discrimination between FTD and AD can be based on a short 
test-battery (verbal ability, visuospatial ability, and verbal memory), when used in the context of a neuropsychological evaluation of qualitative as well as quantitative aspects of test performance.
(47,49,50)
Using a screening instrument based on frontal release signs, aware-ness of social/ethical dilemma in a short story, and the number of preservation errors, FTD was classiﬁ  ed correctly in 83 per cent, 
validated against clinical diagnosis.
(51) The Mini-Mental State 
Examination does not reﬂ  ect the FTD patient’s true competence 
because of inﬂ  uence of motivational and behavioural factors.(52)
Differential diagnosis
Differential diagnosis between FTD and AD and other dementias is

Differential diagnosis between FTD and AD and other dementias is 
often possible based on a careful clinical history and examination, supported by diagnostic tests and brain imaging. Detailed neuropathology remains a gold standard for deﬁ  nite diagnosis 
of FTD and other disorders presenting with FTD-like clinic (Table 4.1.3.3).
The clinical differences between FTD and AD are often obvious

The clinical differences between FTD and AD are often obvious 
at an early stage. The initial stages of FTD are dominated by emo-tional and personality changes, and progressive reduction of speech. Consequently severe dyspraxia, memory failure, and spatial disorientation develop comparatively late with the relative sparing of the temporoparietal occipital cortical areas. In contrast, early-onset AD is characterized by memory failure, dyspraxia, dysgnosia, and impaired sense of locality, whereas habitual personality traits, social competence, and insight are better preserved in agreement 
with the consistent pattern of cortical involvement.
(6) A minority 
of AD cases, about 5 per cent, show a marked frontal-lobe involve-ment at an early stage and consequently also present a frontal-lobe clinical pattern in addition to the temporoparietal symptoms.
The Lund–Manchester consensus
(2) is recommended as a guide-

line for clinical recognition and differential diagnosis of FTD.(53–55)
Table 4.1.3.3  Clinical diagnostic alternatives to FTD
Alzheimer’s disease (AD) with frontal emphasis
Vascular dementia with frontal emphasis Selective white-matter infarction
 Binswanger’s disease
 Multiinfarct dementia with frontal emphasis Strategic infarct dementia (striatal, thalamic)Huntington’s diseaseCreutzfeldt–Jacob diseaseGeneral paresis4.1.3 frontotemporal dementias

SECTION 4  clinical syndromes of adult psychiatry 348
The NINCDS–ADRDA criteria for AD were originally formulated 
with the aim to differentiate between AD and vascular dementia. Varma et al.
(56) found a high sensitivity for probable AD, but also a 
low speciﬁ  city since 77 per cent of pathologically conﬁ  rmed FTD 
cases fulﬁ  lled the NINCDS–ADRDA criteria for AD.
Vascular dementia with frontal emphasis may be caused by 
selective incomplete white-matter infarction, Binswanger’s disease, and frontal and strategic thalamic infarctions. The frontal-lobe dysfunction caused by vascular lesions may closely mimic the course of FTD, when developing gradually without dramatic onset or ﬂ uctuations.
The clinical distinction between FTD and Huntington’s disease 
may be difﬁ  cult when personality changes and psychotic features

may be difﬁ  cult when personality changes and psychotic features 
dominate, and when neurological characteristics are less obvious or appear late in the course. Brain imaging showing striatal involve-ment and genetic analysis may contribute to the diagnosis.
PSP and the rare progressive subcortical gliosis may also show a 
frontal-lobe clinical and imaging pathology. CBD may also present with a dementia of frontal-lobe type in addition to the typical asymmetric akinetic-rigid dystonic syndrome.
(20) These three dis-
eases have grown increasingly important because of studies sug-gesting a linkage to chromosome 17.
(19)
Dementia of the frontal and frontal subcortical type is also found 
in Creutzfeldt–Jakob disease, in the AIDS dementia complex, and in general paresis.
Classiﬁ  cation dilemma
Classiﬁ  cation of frontotemporal dementias must be viewed in a

Classiﬁ  cation of frontotemporal dementias must be viewed in a 
historical perspective. The various clinicopathological entities have been identiﬁ  ed by presence of certain and absence of other clinical 
and pathological features. The current classiﬁ  cation and terminology 
of FTD illustrates, however, the difﬁ  culties of most one-dime nsional
diagnostic systems. A classiﬁ  cation on pure clinical grounds is 
unsatisfactory since symptoms depend more on the starting point in the brain or topography than type of changes, and also on the progression pattern of the disease among brain areas, factors which may vary between cases with structurally identical disorders. A diagnostic classiﬁ  cation should be clinically useful and valid, 
ﬂ exible and open to new ideas. There is a need for combination of 
classiﬁ  cations such as one based on phenomenological syndrome

classiﬁ  cations such as one based on phenomenological syndrome 
kept apart from, and combined with, aetiological including geno-
typical classiﬁ  cation. Hopefully new generations of classiﬁ  cations 
and new diagnostic techniques and treatment strategies will further increase the awareness of FTD in clinical practice and research.
DSM-IV
(1) and ICD-10(57) do not introduce the concepts of 
frontal-lobe dementia or FTD. DSM-IV presents Pick’s disease as ‘One of the pathologically distinct aetiologies among the heteroge-neous group of dementing processes that are associated with fron-totemporal brain atrophy’ . ICD-10 describes ‘dementia in Pick’s disease’ as an early-onset non-Alzheimer degenerative brain disease.
Aetiology and pathogenesis

The FTD is a heterogeneous disease group, but with important clinical features and probably also aetiological factors in common. The clinical and pathological similarities between familial and 
sporadic cases are, however, striking. About 40–50 per centof patients with FLD have a history of similar disorder in a ﬁ  rst-
degree relative.
(23,31) A family history study on 478 ﬁ  rst-degree 
relatives of 74 index patients suffering from FTD reported a 10-fold increase in the incidence of FTD compared with the incidence of FTD in a population study.
(58) A Swedish pedigree with FTD in 
10 out of 21 family members in three generations has been described.
(59)
Several genetic loci for FTD have been identiﬁ  ed at human 
chromosomes 3, 9, and 17 in familial forms of the disease. One FTDP-17 locus has been mapped to a region of chromosome 17 where the tau gene is located. So far 35 different mutations in around 100 families have been identified.
(36) However, tau

(36) However, tau 
mutations seem to be a rare cause of FTD. Dementia of frontal-lobe type has also been linked to chromosome 3p11–12 in a Danish family.
(16) Conﬂ  icting results exist concerning the relation of FTD-
MND to a locus on chromosome 9(60) and to chromosome 19 
and the ApoE-allele pattern.(61) There is no solid proof of an auto-
somal-dominant inheritance in the majority of studies with Pick disease.
Several research groups have recently found mutations in the 
progranulin (PGRN) gene close to the tau gene to result in a loss of function of the growth or maintenance factor PGRN. This leads to a shortage of PRGN and degenerative dementia of the FTD type, including autosomal-dominant FTLD-U linked to chromosome 17 as well as further tau-positive and tau-negative forms.
(17,62) Further 
research has shown that this mechanism may operate also in other neurodegenerative brain disorders including CBD and MND. MND is often linked to FTD-U by a common ubiquitinated protein

(17) and by a frequent concurrence. This protein TDP-43 
forms inclusions in a wide variety of functional brain areas in close correspondence to the symptomatology in the FTD spectrum, the clinical expression of which depends on the individual anatomical starting point and spread of the degeneration. The identiﬁ  cation 
of mutations in PGRN explains why multiple families linked to chromosome 17 lack tau mutations.
(62)
The pattern of degeneration in FTD may be related to a selective 
vulnerability of different brain regions to factors such as oxidative stress, environmental toxins, neurotransmitter dysfunction, and certain mutations. A retrospective study of risk for sporadic FTD reported a signiﬁ  cantly higher prevalence of head trauma and 
thyroid disease.

(63) A prion aetiology has been excluded in FLD and 
also in FTDP-17.
Neurochemical post-mortem studies of FTD have indicated 
abnormalities in serotonin metabolism but no alterations in cholinergic markers have been found.
(64,65)
Treatment and care
Early diagnosis is a prerequisite for adequate treatment and care of the patient and support for the family and other carers involved. It is essential to explain the nature of the patients’ changed behav-iour and current problems. It is important not to forget the children who may still be at school age. It is especially in the social interaction that the earliest signs of the brain disease emerge.
(33)
Alternative optimal placements must be arranged when the patient can no longer be taken care of at home because of disturbing

349
symptoms and lack of insight. T emporary and prolonged hospital 
admissions may be needed to make it possible for the family to cope with the situation. Being a spouse is both physically and emotionally exhausting, causing ill health and socio-economic problems for the family. FTD patients are often restless and stereo-typed with a strong need for physical activity such as walking long distances, which, as well as the comparatively preserved memory, spatial and practical abilities should be channeled in a meaningful way rather than restricted. A well-structured programme for daily activities considering the patients premorbid personality and interests, ‘routinizing therapy’
(66) may be rewarding and minimize 
the need for pharmacological treatment. Prevailing psychotic features and unpredictable aggressive behaviour should be managed by a special psychiatric or psychogeriatric services
(33) also responsible

(33) also responsible 
for support to the spouse and family members who often suffer from social isolation and loneliness.
There is presently no speciﬁ  c pharmacological treatment for the 
underlying degenerative disease in FTD but symptomatic treat-ment with serotonin-boosting antidepressants may be effective in treating some behavioural disturbances.
(67) There are no reports 
that acetylcholinesterase inhibitors improve cognition or behav-iour in FTD, and clinical experience is that the FTD patient may be extremely sensitive to psychotropic medication with disturbing side effects and paradoxical reactions. Various ways to improve progranulin levels may offer future pharmacological treatment for the FTD disorders.
Neary, D., Snowden, J., and Mann, D. (2005). Frontotemporal dementia. 
Lancet Neurology ,4, 771–80 [review].
Alzheimer Research Forum: http://www.alzforum.org/
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351
4.1.4 Prion disease
The human prion diseases, also known as the subacute spongiform 
encephalopathies, have been traditionally classified into Creutzfeldt–Jakob disease ( CJD ), Gerstmann–Sträussler syndrome 
(GSS) (also known as Gerstmann–Sträussler–Scheinker disease), 
and kuru . Although rare, affecting about 1–2 per million world-
wide per annum, remarkable attention has been recently focused on these diseases. This is because of the unique biology of the transmissible agent or prion, and also because bovine spongiform encephalopathy ( BSE), an epidemic bovine prion disease, appears 
to have transmitted to humans as variant CJD ( vCJD ), opening the 
possibility of a signiﬁ  cant threat to public health through dietary 
exposure to infected tissues.
The transmissibility of the human diseases was demonstrated 
with the transmission, by intracerebral inoculation with brain homogenates into chimpanzees, of ﬁ  rst kuru and then CJD in 1966

with the transmission, by intracerebral inoculation with brain homogenates into chimpanzees, of ﬁ  rst kuru and then CJD in 1966 
and 1968, respectively.
(1,2) Transmission of GSS followed in 1981. 
The prototypic prion disease is scrapie , a naturally occurring dis-
ease of sheep and goats, which has been recognized in Europe for over 200 years and which is present in the sheep ﬂ  ocks of many 
countries. Scrapie was demonstrated to be transmissible by inocu-lation in 1936
(3) and the recognition that kuru, and then CJD, 
resembled scrapie in its histopathological appearances led to the suggestion that these diseases may also be transmissible.
(4) Kuru

(4) Kuru 
reached epidemic proportions amongst the Fore linguistic group in the Eastern Highlands of Papua New Guinea and was transmitted by ritual cannibalism. Since the cessation of cannibalism in the 1950s the disease has declined but a few cases still occur as a result of the long incubation periods in this condition, which may exceed 50 years.
(5) The term Creutzfeldt–Jakob disease was introduced 
by Spielmeyer in 1922 bringing together the case reports published by Creutzfeldt and Jakob. Several of these cases would not meet modern diagnostic criteria for CJD and indeed it was not until the demonstration of transmissibility allowed diagnostic criteria to be reassessed and reﬁ  ned that a clear diagnostic entity developed.

All these diseases share common histopathological features; the classical triad of spongiform vacuolation (affecting any part of the cerebral grey matter), astrocytic proliferation, and neuronal loss, may be accompanied by the deposition of amyloid plaques.
Aetiology
Prion diseases of both humans and animals are associated with the accumulation in the brain of an abnormal, partially protease-resistant, isoform of a host-encoded glycoprotein known as prion protein (PrP). The disease-related isoform, PrP
Sc, is derived from 
its normal cellular precursor, PrPC, by a post-translational process 
that involves a conformational change. PrPC is rich in α-helical 
structure while PrPSc appears to be predominantly composed of 
β-sheet structure. According to the ‘protein-only’ hypothesis,(6) an 
abnormal PrP isoform(7) is the principal, and possibly the sole, 
constituent of the transmissible agent or prion. PrPSc is hypothe-

sized to act as a conformational template, promoting the conver-sion of PrP
C to further PrPSc. PrPC appears to be poised between two radically different folding states, and α- and β-forms of PrP 
can be inter-converted in suitable conditions.(8) Soluble β-PrP 
aggregates in physiological salt concentrations to form ﬁ  brils with 
morphological and biochemical characteristics closely similar to PrP
Sc. A molecular mechanism for prion propagation can now be 
proposed.(8) Prion replication, with recruitment of PrPC into the 
aggregated PrPSc isoform, may be initiated by a pathogenic muta-
tion (resulting in a PrPC predisposed to form β-PrP) in inherited 
prion diseases, by exposure to a ‘seed’ of PrPSc in acquired cases, 
or as a result of the spontaneous conversion of PrPC to β-PrP (and

or as a result of the spontaneous conversion of PrPC to β-PrP (and 
subsequent formation of aggregated material) as a rare stochastic event in sporadic prion disease.
The human PrP gene ( PRNP ) is a single copy gene located on the 
short arm of chromosome 20 and was an obvious candidate for genetic linkage studies in the familial forms of CJD and GSS, which both showed an autosomal dominant pattern of disease segrega-tion. A turning point in understanding the human prion diseases was the identiﬁ  cation of mutations in the prion protein gene  in 
familial CJD and GSS in 1989. The ﬁ  rst mutation to be identiﬁ  ed 
inPRNP  was in a family with CJD and constituted a 144 bp inser-
tion into the coding sequence.
(9) A second mutation was reported 
in two families with GSS and genetic linkage was confirmed between this missense variant at codon 102 and GSS, conﬁ  rming

in two families with GSS and genetic linkage was confirmed between this missense variant at codon 102 and GSS, conﬁ  rming 
that GSS was an autosomal dominant Mendelian disorder.
(10)
Uniquely, these diseases are therefore both inherited and transmis-sible. Current evidence suggests that around 15 per cent of prion diseases are inherited and over 30 coding mutations in PRNP  are 
now recognized.
With the exception of the rare iatrogenic CJD cases mentioned 
above, most prion disease occurs as sporadic CJD. While, by deﬁ  ni-

tion, there will not be a family history in sporadic cases, mutations are seen in occasional apparently sporadic cases, as with a late-onset disease the family history may not be apparent or non-paternity may occur. However, in the majority of sporadic CJD cases there is neither a coding mutation nor a history of iatrogenic exposure. Human prion diseases can therefore be subdivided into inherited, sporadic, and acquired forms. However, a common PrP polymor-phism at residue 129, where either methionine or valine can be encoded, is a key determinant of genetic susceptibility to acquired and sporadic prion diseases, the large majority of which occur in homozygous individuals.
(11,12)  This protective effect of PRNP
codon 129 heterozygosity is also seen in some of the inherited prion diseases.

The aetiology of sporadic CJD remains unclear. It has been 
speculated that these cases might arise from somatic mutation of PRNP  or spontaneous conversion of PrP
C to PrPSc as a rare 
stochastic event. The alternative hypothesis, in which such cases arise as a result of exposure to an environmental source of either human or animal prions, is not supported by epidemiological evidence.
(13)
A major problem for the ‘protein-only’ hypothesis of prion 
propagation has been how to explain the existence of multiple isolates or strains of prions, with distinct biological properties. Understanding how a protein-only infectious agent could encode such phenotypic information has been of considerable biological interest. However, it is now clear that prion strains can be distin-guished by differences in the biochemical properties of PrP
Sc. Prion

Sc. Prion 
strain diversity appears to be encoded by differences in PrPcon formation and pattern of glycosylation.
(14) A molecular strain 4.1.4 prion disease

SECTION 4  clinical syndromes of adult psychiatry 352
typing approach based on these characteristics has allowed the 
identiﬁ  cation of four main types amongst CJD cases, sporadic and 
iatrogenic CJD being of PrPSc types 1–3, while all vCJD cases are 
associated with a distinctive type 4 PrPSc type.(14,15) A similar PrPSc
type to that seen in vCJD is seen in BSE and BSE when transmitted 
to several other species. Such molecular strain typing strongly sup-ported the hypothesis that vCJD was human BSE. This conclusion was strengthened by subsequent transmission studies of vCJD into both transgenic and conventional mice which argued that cattle BSE and vCJD were caused by the same strain.
(16,17) Such studies 
are allowing a molecular classiﬁ  cation of human prion diseases. 
Two such classiﬁ  cations are in use: no internationally agreed clas-
siﬁ cation has yet emerged and it is likely that additional PrPSc types 
or strains will be identiﬁ  ed.(15,18) Molecular classiﬁ  cation may

or strains will be identiﬁ  ed.(15,18) Molecular classiﬁ  cation may 
well open new avenues of epidemiological investigation and offer insights into causes of ‘sporadic’ CJD. The ability of a protein to encode a disease phenotype has important implications in biology, as it represents a non-Mendelian form of transmission. It would be surprising if this mechanism had not been used more widely during evolution such that prion biology may prove to be of far wider relevance.
Transmission of prion diseases between different mammalian 
species is limited by a so-called ‘species barrier’ . Early studies of the molecular basis of the species barrier argued that it principally resided in differences in PrP primary structure between the species from which the inoculum was derived and the inoculated host. Transgenic mice expressing hamster PrP were, unlike wild-type mice, highly susceptible to infection with hamster prions.

(19) That 
most sporadic and acquired CJD occurred in individuals homozy-gous at PRNP  polymorphic codon 129 supported the view that 
prion propagation proceeded most efﬁ  ciently when the interacting 
PrP
Sc and PrPC were of identical primary structure.(12) However, it 
has been long recognized that prion strain type affects ease of transmission to another species. Interestingly, with BSE prions the strain component to the barrier seems to predominate, with BSE not only transmitting efﬁ  ciently to a range of species, but main-
taining its transmission characteristics even when passaged through an intermediate species with a distinct PrP gene.
(20) The term 
‘species-strain barrier’ or simply ‘transmission barrier’ may be preferable.
(21) Both PrP amino acid sequence and strain type affect 
the 3D structure of glycosylated PrP which will presumably, in turn, affect the efficiency of the protein–protein interactions thought to determine prion propagation.

Mammalian PrP genes are highly conserved. Presumably only a 
restricted number of different PrP
Sc conformations (that are highly 
stable and can therefore be serially propagated) will be permissible thermodynamically and will constitute the range of prion strains seen in mammals. While a signiﬁ  cant number of different such 
PrP
Sc conformations may be possible amongst the range of mam-
malian PrPs, only a subset of these would be allowable for a given single mammalian PrP . Substantial overlap between the favoured conformations for PrP
Sc derived from species A and species B 
might therefore result in relatively easy transmission of prion dis eases
between these two species, while two species with no preferred PrP
Sc conformations in common would have a large barrier to

Sc conformations in common would have a large barrier to 
transmission (and indeed transmission would necessitate a change of strain type). According to such a conformational selection model
(21)
of a prion transmission barrier, BSE may represent a thermody-
namically highly favoured PrPSc conformation that is permissive for PrP expressed in a wide range of different species, accounting 
for the remarkable promiscuity of this strain in mammals. Contribution of other components to the species barrier are possible and may involve interacting co-factors which mediate the efﬁ ciency of prion propagation, although no such factors have yet 
been identiﬁ  ed.
Additional data has further challenged our understanding of 
transmission barriers.
(22) The assessment of species barriers has

(22) The assessment of species barriers has 
relied on the development of a clinical disease in inoculated ani-mals. However, it is now clear that subclinical prion infections  are 
sometimes established on prion inoculation of a second species.
(23)
Such animals harbour high levels of prion infectivity but do not develop clinical disease during a normal lifespan. The existence of such subclinical carrier states of prion infection has important potential animal and public health implications and argues against direct neurotoxicity of prions.
The transmission barrier between cattle BSE and humans cannot 
be directly measured but can be modelled in transgenic mice expressing human PrP
C, which produce human PrPSc when chal-

lenged with human prions. Long-term transmission studies have been carried out using such ‘humanized’ mice to both to characterize the distinct prion strains causing human disease and to model human susceptibility to infection with BSE and other prions.
(24) While these transgenic mouse models have been able to 
faithfully propagate human prion strains(14,16,25) and recapitulate 
the characteristic neuropathology of vCJD,(26) there are important

the characteristic neuropathology of vCJD,(26) there are important 
caveats in extrapolating from such animal models to human susceptibility. However, these studies have found a much higher infection rate in transgenic mice expressing human PrP M129 than mice expressing human PrP V129 when challenged with either BSE or vCJD prions, and demonstrated that BSE prion infection can produce disease phenotypes resembling sporadic CJD infection of these mice and also novel prion strain phenotypes. Most recently, these studies have argued that the vCJD phenotype may only be expressed in the presence of the M form of human PrP .
(27) While

(27) While 
this would imply that only those humans expressing human PrP M129 may develop the vCJD phenotype, this does not mean that VV individuals are completely resistant to BSE prion infection—but rather that if infected they would show a different phenotype.
(27)
Modelling of susceptibility of the MV genotype suggests that several different phenotypes, all distinct from vCJD, may be possible when infected with BSE or vCJD prions.
(28)
Clinical features and diagnosis

(28)
The human prion diseases can be divided aetiologically into inherited, sporadic, and acquired forms with CJD, GSS, and kuru now seen as clinicopathological syndromes within a wider spec-trum of disease. Kindreds with inherited prion disease have been described with phenotypes of classical CJD, GSS, and also with other neurodegenerative syndromes including fatal familial insom-nia. Some kindreds show remarkable phenotypic variability which can encompass both CJD- and GSS-like cases as well as other cases which do not conform to either CJD or GSS phenotypes and which indeed readily mimic, and are frequently misdiagnosed as, many other neurodegenerative conditions. Inherited prion diseases are a frequent cause of pre-senile dementia and a family history is not always apparent: PRNP  should be analysed in all suspected cases of

CJD, and considered in all early-onset dementia and ataxias. Cases diagnosed by PRNP  analysis have been reported which are not only

353
clinically atypical but which lack the classical histological features 
entirely. Signiﬁ  cant clinical overlap exists with familial Alzheimer’s 
disease, Pick’s disease, frontal lobe degeneration of non-Alzheimer type, and amyotrophic lateral sclerosis with dementia. Although classical GSS is described below it now seems more sensible to designate the familial illnesses as inherited prion diseases and then to subclassify these according to mutation. Acquired prion diseases include iatrogenic CJD, kuru, and now vCJD. Sporadic prion dis-eases at present consist of CJD and atypical variants of CJD. Cases

lacking the characteristic histological features of CJD have been transmitted. As there are at present no equivalent aetiological diag-nostic markers for sporadic prion diseases to those for the inherited diseases, it cannot yet be excluded that more diverse phenotypic variants of sporadic prion disease exist. The key clinical features and investigations for the diagnosis of prion disease are given in the Table 4.1.4.1.
Sporadic prion disease
CJD
The core clinical syndrome of classic CJD is of a rapidly progressive multifocal dementia usually with myoclonus. The onset is usually in the 45–75-year age group with peak onset between 60 and 65 years. The clinical progression is typically over weeks progressing to aki-netic mutism and death often in 2–3 months. Around 70 per cent of cases die in under 6 months. Prodromal features, present in around a third of cases, include fatigue, insomnia, depression, weight loss, headaches, general malaise, and ill-deﬁ  ned pain sensa-

tions. In addition to mental deterioration and myoclonus, frequent additional neurological features include extrapyramidal signs, cerebellar ataxia, pyramidal signs, and cortical blindness. About 10 per cent of cases present initially with cerebellar ataxia.
Routine haematological and biochemical investigations are 
normal although occasional cases have been noted to have raised 
serum transaminases or alkaline phosphatase. There are no 
immunological markers and acute phase proteins are not elevated. Examination of the ce rebrospinal ﬂ  uid is normal 14-3-3 protein is 
usually elevated in CJD and is a useful adjunct to diagnosis in the appropriate clinical context.
(29) It is also positive in recent cerebral 
infarction or haemorrhage and in viral encephalitis, although these 
conditions do not usually present diagnostic confusion with CJD. 
It may also be elevated in rapidly progressive Alzheimer’s disease, which may be difﬁ  cult to clinically distinguish from CJD. Neuronal

It may also be elevated in rapidly progressive Alzheimer’s disease, which may be difﬁ  cult to clinically distinguish from CJD. Neuronal 
speciﬁ  c enolase (NSE) and S-100b may be also elevated although 
also are not speciﬁ  c for CJD and represent markers of neuronal 
injury
(30,31)  Neuroimaging with CT or MRI is crucial to exclude 
other causes of subacute neurological illness but MRI has become increasingly useful in diagnosis of sporadic CJD, showing high sig-nal in the striatum and/or cerebral cortex in FLAIR or diffusion-weighted images.
(32) Cerebral and cerebellar atrophy may be pres-
ent in longer duration cases. The electroencephalogram (EEG) may show characteristic pseudoperiodic sharp wave activity, which is very helpful in diagnosis but present only in around 70 per cent of cases. T o some extent demonstration of a typical EEG is dependent on the number of EEGs performed and serial EEG is indicated to try and demonstrate this appearance.

Prospective epidemiological studies have demonstrated that 
cases with a progressive dementia, and two or more of the follow-ing: myoclonus; cortical blindness; pyramidal, cerebellar, or extra-pyramidal signs; or akinetic mutism in the setting of a typical EEG nearly always turn out to be conﬁ  rmed as histologically deﬁ  nite 
CJD if neuropathological examination is performed.
Neuropathological conﬁ  rmation of CJD is by demonstration of 
spongiform change, neuronal loss, and astrocytosis. PrP amyloid 
plaques are usually not present in CJD although PrP immunohis-
tochemistry, using appropriate pre-treatments, will nearly always be positive. Protease resistant PrP , seen in all the currently recognized Table 4.1.4.1  Diagnosis of prion disease
Sporadic (classical) CJD
X  Rapidly progressive* dementia with two or more of myoclonus, cortical 
blindness, pyramidal signs, cerebellar signs, extrapyramidal signs, akinetic 
mutism
X Most cases age 45–75

mutism
X Serial EEG shows pseudoperiodic complexes in most cases
X CSF 14-3-3 protein usually positive
X  CT normal or atrophy, MRI may show high signal in the striatum and/or 
cerebral cortex in FLAIR or diffusion-weighted images
X  PRNP  analysis: no pathogenic mutations, most are 129 MM (VV and MV 
may be longer duration, clinically atypical and EEG less often positive)
X  Brain biopsy in highly selected cases (to exclude treatable alternative 
diagnoses): PrP immunocytochemistry or Western blot for PrPSc types 1–3
Iatrogenic CJD
X  Progressive cerebellar syndrome and behavioural disturbance or classical 
CJD-like syndrome with history of iatrogenic exposure to human prions 
(pituitary-derived hormones, tissue grafting, or neurosurgery)
X May be young

X EEG, CSF, and MRI generally less helpful than in sporadic cases
X  PRNP  analysis: no pathogenic mutations, most are 129 homozygotes
Variant CJD
X  Early features: depression, anxiety, social withdrawal, peripheral sensory 
symptoms
X  Cerebellar ataxia, chorea, or athetosis often precedes dementia, advanced 
disease as sporadic CJD
X Most in young adults; however, age at onset 12–74 years seen
X EEG non-speciﬁ  c slow waves, CSF 14-3-3 may be elevated or normal
X  MRI: pulvinar sign usually present (particularly using FLAIR sequence) but 
may be late feature
X PRNP  analysis: no mutations, all 129 MM to date
X  Tonsil biopsy: characteristic PrP immunostaining and PrPSc on Western blot

X  Tonsil biopsy: characteristic PrP immunostaining and PrPSc on Western blot 
(type 4t)
Iatrogenic vCJD
X  Has occurred in recipients of blood transfusion from a donor who 
subsequently developed clinical vCJD
X  Known recipients of implicated blood or blood products in the UK have 
been notiﬁ  ed of their risk status
X Clinical features and investigations as for primary vCJD
Inherited prion disease
X  Varied clinical syndromes between and within kindreds: should consider in 
all pre-senile dementias and ataxias irrespective of family history
X  PRNP  analysis: diagnostic, codon 129 genotype may predict age at onset in 
pre-symptomatic testing
* Clinical duration typically 6 months or less but high variability: type 1 PrPSc associated 
with short duration (~8 weeks); ~10% have duration >2 years.4.1.4 prion disease

SECTION 4  clinical syndromes of adult psychiatry 354
prion diseases, can be demonstrated by immunoblotting of brain 
homogenates. PRNP  analysis is important to exclude pathogenic 
mutations. Genetic susceptibility to CJD has been demonstrated in that most cases of classical CJD are homozygous with respect to the common 129 polymorphism of PrP (see aetiology).
Atypical forms of CJD

Atypical forms of CJD are well recognized. Around 10 per cent of cases of CJD have a much more prolonged clinical course with a disease duration of over 2 years. These cases may represent the occasional occurrence of CJD in individuals heterozygous for PrP polymorphisms. Around 10 per cent of CJD cases present withcerebellar ataxia rather than cognitive impairment, so-called ataxic CJD. Heidenhain’s variant of CJD refers to cases in which cortical blindness predominates with severe involvement of the occipital lobes. The panencephalopathic type of CJD refers to cases with extensive degeneration of the cerebral white matter in addition to spongiform vacuolation of the grey matter and has been predomi-nately reported from Japan.
Amyotrophic variants of CJD have been described with promi-
nent early muscle wasting. However, most cases of dementia with 
amyotrophy are not experimentally transmissible and their rela-

tionship with CJD is unclear. Most cases are probably variants of motor neurone disease with associated dementia. Amyotrophic features in CJD are usually seen in late disease when other features are well established.
Acquired prion diseases
While human prion diseases can be transmitted to experimental animals by inoculation, they are not contagious in humans. Documented case to case spread has only occurred during ritu-al cannibalistic practices (kuru) or following accidental inocu-lation with prions during medical or surgical procedures(iatrogenic CJD).
Kuru
Kuru reached epidemic proportions amongst a deﬁ  ned population 
living in the Eastern Highlands of Papua New Guinea.(33) The ear-

Kuru
liest cases are thought to date back to the early part of the century. Kuru affected the people of the Fore linguistic group and their neighbours with whom they intermarried. Kuru predominantly affected women and children (of both sexes), with only 2 per cent of cases in adult males and was the commonest cause of death 
amongst women in affected villages. It was the practice in these

amongst women in affected villages. It was the practice in these 
communities to engage in consumption of dead relatives as a mark of respect and mourning. Women and children predominantly ate the brain and internal organs, which is thought to explain the differential age and sex incidence. Preparation of the cadaver for consumption was performed by the women and children such that other routes of exposure may also have been relevant. It is thought that the epidemic related to a single sporadic CJD case occurring in the region some decades earlier. Epidemiological studies provided 
no evidence for vertical transmission, since most of the children

no evidence for vertical transmission, since most of the children 
born after 1956 (when cannibalism had effectively ceased) and all of those born after 1959 of mothers affected with or incubating kuru were unaffected. From the age of the youngest affected patient, the shortest incubation period is estimated as 4.5 years, although may have been shorter, since time of infection was usually unknown. The disease has gradually declined in incidence although a small 
number of cases have been documented in recent years with incu-bation periods which may exceed 50 years.
(5)
Kuru affects both sexes and onset of disease has ranged from age

(5)
Kuru affects both sexes and onset of disease has ranged from age 
5 to over 60. The mean clinical duration of illness is 12 months with a range of 3 months to 3 years; the course tends to be shorter in children. The central clinical feature is progressive cerebellar ataxia. In sharp contrast to CJD, dementia is usually absent, even in the latter stages, although in the terminal stages many patients have their faculties obtunded. The occasional case in which gross demen-tia occurs is in marked contrast to the clinical norm. Detailed clini-cal descriptions have been given by a number of observers and the disease does not appear to have changed in features at different stages of the epidemic. A prodrome and three clinical stages are recognized:
(a) Prodromal stage

Kuru typically begins with prodromal symptoms consisting of headache, aching of limbs, and joint pains, which can last for several months.
(b) Ambulatory stage
Kuru was frequently self-diagnosed by patients at the earliest onset of unsteadiness in standing or walking, or of dysarthria or diplopia. At this stage there may be no objective signs of disease. Gait ataxia however worsens and patients develop a broad-based gait, truncal instability, and titubation. A coarse postural tremor is usually present 
and accentuated by movement; patients characteristically hold

and accentuated by movement; patients characteristically hold 
their hands together in the midline to suppress this. Standing with feet together reveals clawing of toes to maintain posture. This marked clawing response is regarded as pathognomonic of kuru. Patients often become withdrawn at this stage and occasionally develop a severe reactive depression. Prodromal symptoms tend to disappear. Astasia and gait ataxia worsen and the patient requires a stick for walking. Intention tremor, dysmetria, hypotonia, and dysdiadochokinesis develop. Although eye movements are ataxic 
and jerky, nystagmus is rarely seen. Strabismus, usually convergent, 
may occur particularly in children. This strabismus does not appear to be concomitant or paralytic and may ﬂ  uctuate in both extent

may occur particularly in children. This strabismus does not appear to be concomitant or paralytic and may ﬂ  uctuate in both extent 
and type sometimes disappearing later in the clinical course. Photophobia is common and there may be an abnormal cold sensi-tivity with shivering and piloerection even in a warm environment. Te n do n  re ﬂ  exes are reduced or normal and plantar responses are 
ﬂ exor. Dysarthria usually occurs. As ataxia progresses the patient 
passes from the ﬁ  rst (ambulatory) stage to the second (sedentary) 
stage. The mean clinical duration of the ﬁ  rst stage is around 
8 months and correlates closely with total duration.
(c) Sedentary stage
At this stage patients are able to sit unsupported but cannot walk. Attempted walking with support leads to a high steppage, wide-based gait with reeling instability, and ﬂ  inging arm movements in 
an attempt to maintain posture. Hyperreﬂ  exia is seen although 
plantar responses usually remain ﬂ  exor with intact abdominal

plantar responses usually remain ﬂ  exor with intact abdominal 
reﬂ exes. Clonus is characteristically short-lived. Athetoid and cho-
reiform movements and Parkinsonian tremors may occur. There is no paralysis, although muscle power is reduced. Obesity is com-mon at this stage but may be present in early disease associated with bulimia. Characteristically, there is emotional lability and bizarre uncontrollable laughter, which has led to the disease being

355
referred to as ‘laughing death’ . There is no sensory impairment. 
In sharp contrast to CJD, myoclonic jerking is rarely seen. EEG is 
usually normal or may show non-speciﬁ  c changes. This stage lasts 
around 2–3 months. When truncal ataxia reaches the point where the patient is unable to sit unsupported, the third or tertiary stage is reached.
(d) Tertiary stage
Hypotonia and hyporeﬂ  exia develop and the terminal state is 
marked by ﬂ  accid muscle weakness. Plantar responses remain ﬂ  ex-
or and abdominal reﬂ  exes intact. Progressive dysphagia occurs and 
patients become incontinent of urine and faeces. Inanition and emaciation develop. Transient conjugate eye signs and dementia may occur. Primitive reﬂ  exes develop in occasional cases. Brainstem 
involvement and both bulbar and pseudobulbar signs occur. Respiratory failure and bronchopneumonia eventually lead to death. The tertiary stage lasts 1–2 months.

Iatrogenic transmission of CJD has occurred by accidental inocula-tion with human prions as a result of medical procedures. Such iatrogenic routes include the use of inadequately sterilized neuro-surgical instruments, dura mater and corneal grafting, and use of human cadaveric pituitary-derived growth hormone or gonado-trophin. It is of considerable interest that cases arising from intra-cerebral or optic inoculation manifest clinically as classical CJD, with a rapidly progressive dementia, while those resulting from peripheral inoculation, most notably following pituitary-derived growth hormone exposure, typically present with a progressive cerebellar syndrome, and are in that respect somewhat reminiscent of kuru. Unsurprisingly the incubation period in intracerebral cases is short (19–46 months for dura mater grafts) as compared to peripheral cases (typically 15 years or more). There is evidence for genetic susceptibility to iatrogenic CJD with an excess of codon 129 homozygotes

(11) (see aetiology).
Epidemiological studies have not shown increased risks of 
particular occupations that may be exposed to human or animal prions, although individual CJD cases in two histopathology technicians, a neuropathologist, and a neurosurgeon have been documented. While there have been concerns that CJD may be transmissible by blood transfusion, extensive epidemiological anal-ysis in the UK has found that the frequency of blood transfusion and donation was no different in over 200 cases of CJD and a matched control population.
(34) Recipients of blood transfusions 
who developed CJD had clinical presentations similar to those of sporadic CJD patients and not to the more kuru-like iatrogenic cases arising from peripheral exposure to human prions. Furthermore, experimental transmission studies have shown only weak evidence for infectivity in blood, even when inoculated via the most efﬁ  cient (intracerebral) route. Iatrogenic (secondary)

vCJD related to blood transfusion has however been recognized (see below).
In late 1995, two cases of sporadic CJD were reported in the UK in teenagers.
(35) Only four cases of sporadic CJD had previously been 
recorded in teenagers, and none of these cases occurred in the UK. In addition, both cases were unusual in having kuru-type plaques, a ﬁ nding seen in only around 5 per cent of CJD cases. Soon after-

wards a third very young sporadic CJD case occurred. These cases caused considerable concern and the possibility was raised that they might suggest a link with BSE. By March 1996, further extremely young onset cases were apparent and review of the his-tology of these cases showed a remarkably consistent and unique pattern. These cases were named ‘new variant’ CJD although it was clear that they were also rather atypical in their clinical presenta-tion; in fact most cases did not meet the accepted clinical diagnos-tic criteria for probable CJD. Extensive studies of archival cases of CJD or other prion diseases failed to show this picture and it seemed that it did represent the arrival of a new form of prion disease in the UK. The statistical probability of such cases occur-ring by chance was vanishingly small and ascertainment bias seemed most unlikely as an explanation. It was clear that a new risk factor for CJD had emerged and appeared to be speciﬁ  c to the UK.

The UK Government advisory committee on spongiform encepha-
lopathy (SEAC) concluded that, while there was no direct evidence for a link with BSE, exposure to speciﬁ  ed bovine offal (SBO) prior

to the ban on its inclusion in human foodstuffs in 1989, was the most likely explanation. A case of vCJD was soon after reported in France. Direct experimental evidence that vCJD is caused by BSE was provided by molecular analysis of human prion strains and transmission studies in transgenic and wild-type mice (see aetiol-ogy). While it is now clear that vCJD is caused by infection with BSE prions, it is unclear why this particular age group should be affected and why none of these cases had a pattern of unusual occupational or dietary exposure to BSE. However, very little is known of which foodstuffs contained high-titre bovine offal. It is possible that certain foods containing particularly high titres were eaten predominately by younger people. An alternative is that young people are more susceptible to BSE following dietary expo-sure or that they have shorter incubation periods. A possible age-related co-factor could be coexistent infection involving lymphoid tissue, for example

more susceptible to BSE following dietary expo-sure or that they have shorter incubation periods. A possible age-related co-factor could be coexistent infection involving lymphoid tissue, for example tonsillar infection. It is important to appreciate that BSE contaminated feed was fed to sheep, pigs, and poultry and that although there is no evidence of natural transmission to these species, it would be prudent to remain open minded about other dietary exposure to novel animal prions.

vCJD has an insidious clinical onset and its early features are 
highly non-speciﬁ  c. The clinical presentation is often with behav-
ioural and psychiatric disturbances and in some cases with sensory disturbance. Initial referral has frequently been to a psychiatrist and the most prominent feature is depression but anxiety, social withdrawal, and behavioural change is frequent. Suicidal ideation is infrequent and response to antidepressants poor. Delusions, which are complex and unsustained, are common. Other features include emotional lability, aggression, insomnia, and auditory and visual hallucinations. A prominent early feature in some is dysaes-thesiae or pain in the limbs or face or pain, which is persistent rather 
than intermittent and unrelated to anxiety levels. A minority of

than intermittent and unrelated to anxiety levels. A minority of 
cases have been noted to have forgetfulness or mild gait ataxia from an early stage but in most cases overt neurological features are not apparent until some months into the clinical course. In most patients a progressive cerebellar syndrome develops with gait and limb ataxia. Overt dementia then occurs with inevitable progres-sion to akinetic mutism. Myoclonus is seen in most patients, and chorea is often present which may be severe in some patients. Cortical blindness develops in a minority of patients in the late 4.1.4 prion disease

SECTION 4  clinical syndromes of adult psychiatry 356
stages of disease. Upgaze paresis, an uncommon feature of classical 
CJD, has been noted in some patients. The age at onset in the initial 14 cases reported ranged from 16 to 48 years (mean 29 years) and the clinical course was unusually prolonged (9–35 months, median 14 months). The age range of cases has since broadened, with ages at onset ranging from 12 to 74 years, although the mean remains around 28 years. The EEG is abnormal, most frequently showing generalized slow wave activity, but without the pseudoperiodic pat-tern seen in most sporadic CJD cases. Neuroimaging by CT is either normal or shows only mild atrophy. The most useful non-invasive investigation in advanced cases is MR neuroimaging, particularly the FLAIR sequence.
(36) Early case reports noted bilateral increased 
signal in the posterior thalamus (pulvinar) on T2-weighted images.(37)
A retrospective review of 36 histologically conﬁ  rmed cases of vCJD

A retrospective review of 36 histologically conﬁ  rmed cases of vCJD 
suggested that the ‘pulvinar sign’ occurred frequently in advanced cases of vCJD
(38) with a sensitivity and speciﬁ  city of up to 86 and 
96 per cent, respectively. However, this sign appears a late feature of the disease process. Histologically conﬁ  rmed cases of vCJD with 
minimal or absent pulvinar changes at a mean 10.5 months during an illness of mean 15 months duration were identiﬁ  ed in this series. 
Figures of 81 per cent sensitivity and 94 per cent speciﬁ  city have 
also been reported in a series including 27 cases of vCJD diagnosed by tonsil biopsy.
(39) As these studies suggest, the pulvinar sign is 
not speciﬁ  c for vCJD. These MRI appearances are described in

not speciﬁ  c for vCJD. These MRI appearances are described in 
sporadic CJD and paraneoplastic limbic encephalitis, both of which are important considerations in the differential diagnosis of patients with suspected vCJD. Pulvinar signal change on MRI is also report-ed in a number of rare conditions, which might otherwise bedistinguished from vCJD on clinical grounds such as benign intra-cranial hypertension, status epilepticus associated with cat scratch disease, Alpers’ disease, and post-infectious encephalitis. The absence of pulvinar sign does not exclude a diagnosis of vCJD.
T onsillar biopsy remains the most sensitive and speciﬁ  c diagnos-
tic procedure for vCJD.
(39–43) T onsillar PrPSc is uniformly present

(39–43) T onsillar PrPSc is uniformly present 
in clinically affected cases of vCJD but not in other forms of human prion disease, including iatrogenic CJD associated with use of human cadaveric-derived pituitary hormones, arguing that this distinctive pathogenesis relates to effect of prion strain rather than to a peripheral route of infection.
(41–43) As infection of lymphore-
ticular tissues is thought to precede neuroinvasion, and indeed has been detected in archived surgical samples removed prior to devel-opment of vCJD,
(44,45)  it is likely to allow ﬁ  rm diagnosis at the early 
clinical stage or indeed pre-clinically.(46) The PrPSc type detected

clinical stage or indeed pre-clinically.(46) The PrPSc type detected 
on Western blot in vCJD tonsil has a characteristic pattern desig-nated type 4t. A positive tonsil biopsy obviates the need for brain biopsy, which may otherwise be considered in such a clinical context to exclude alternative, potentially treatable diagnoses. CSF 14-3-3 protein may be elevated or normal. PRNP  analysis is essen-
tial to rule out pathogenic mutations, as the inherited prion dis-eases present in younger patients and may clinically mimic vCJD. It is particularly important to exclude mutations prior to tonsil biopsy. Remarkably, to date all clinical cases of vCJD have been of thePRNP  codon 129 MM genotype (see aetiology).
The neuropathological appearances of vCJD are striking and rela-

tively consistent, generally allowing differentiation from other forms of prion disease. While there is widespread spongiform change, gli-osis and neuronal loss, most severe in the basal ganglia and thala-mus, the most remarkable feature is abundant PrP amyloid plaques in cerebral and cerebellar cortex. These consist of kuru-like, ‘ﬂ  orid’ (surrounded by spongiform vacuoles) and multicentric plaque 
types. The ‘ﬂ  orid’ plaques, seen previously only in scrapie, are a 
consistent feature. There is also abundant pericellular PrP deposi-tion in the cerebral and cerebellar cortex. A further unusual feature is extensive PrP deposition in the molecular layer of the cerebel-lum. Western blot analysis (molecular strain typing, see aetiology) of brain tissue demonstrates PrP
Sc type 4, which is pathognomonic 
of vCJD.
Some of the features of vCJD are reminiscent of kuru, in which

of vCJD.
Some of the features of vCJD are reminiscent of kuru, in which 
behavioural changes and progressive ataxia predominate. In addi-tion, peripheral sensory disturbances are well recognized in the kuru prodrome. Kuru plaques are seen in around 70 per cent of cases and are especially abundant in younger kuru cases. The obser-vation that iatrogenic prion disease related to peripheral exposure to human prions has a more kuru-like than CJD-like clinical picture may well be relevant and would be consistent with a periph-eral prion exposure.
The relatively stereotyped clinical presentation and neuropathol-
ogy of vCJD contrasts sharply with sporadic CJD. This may be because vCJD is caused by a single prion strain and may also suggest that a relatively homogeneous genetically susceptible sub-
group of the population with short incubation periods to BSE has 
been selected to date.
Secondary (iatrogenic) vCJD

The prominent lymphoreticular involvement raised early concerns that vCJD may be transmissible by blood transfusion. Indeed the tissue distribution is similar to that of ovine scrapie where prionae-mia has been demonstrated experimentally. In 2004, two transfusion-associated cases of vCJD prion infection were reported amongst a small cohort of patients identiﬁ  ed as having received blood 
from a donor who subsequently developed vCJD. One patient had a typical clinical course of vCJD although the diagnosis was not made until autopsy, and had the PRNP  codon 129 MM genotype. 
The second, who died of an unrelated condition, was found to have prion infection at autopsy. This patient had the PRNP  codon

The second, who died of an unrelated condition, was found to have prion infection at autopsy. This patient had the PRNP  codon 
129 MV genotype which is associated with relative resistance to prion disease. Subsequently two further patients have been diag-nosed with vCJD dur ing life from this group of 23 known surviving 
recipients of implicated blood. That 4/23 patients have been infected, 
three dying of vCJD, in each case following transfusion with a single unit of implicated red cells, suggests the risk to recipients of blood from a silently infected donor is very substantial. The incubation period in the clinical cases was 6–7 years. Since 2003, all known recipients of implicated blood have been notiﬁ  ed of their status. 
Over 6000 individuals in the UK have been exposed to blood prod-ucts prepared from large donor pools containing blood from a donor who went on to develop vCJD. None of these individuals, predominantly haemophiliacs, have yet developed vCJD.

Inherited prion diseases
Gerstmann–Sträussler–Scheinker disease
The ﬁ  rst case was described by Gerstmann in 1928 and was followed 
by a more detailed report on seven other affected members of the same family in 1936. The classical presentation of GSS is with a chronic cerebellar ataxia accompanied by pyramidal features, with dementia occurring later in a much more prolonged clinical course than that seen in CJD. The mean duration is around 5 years, with

357
onset usually in either the third or fourth decades. Histologically, 
the hallmark is the presence of multicentric amyloid plaques. Spongiform change, neuronal loss, astrocytosis, and white matter loss are also usually present. Numerous GSS kindreds from several countries (including the original Austrian family described by Gerstmann, Sträussler, and Scheinker in 1936) have now been dem-onstrated to have mutations in the PrP gene. GSS is an autosomal dominant disorder which can now be classiﬁ  ed within the spectrum 
of inherited prion disease.
The identiﬁ  cation of one of the pathogenic PrP gene mutations in 
a case with neurodegenerative disease allows not only molecular diagnosis of an inherited prion disease but also its subclassiﬁ  cation

a case with neurodegenerative disease allows not only molecular diagnosis of an inherited prion disease but also its subclassiﬁ  cation 
according to mutation (see Fig. 4.1.4.1). Over 30 pathogenic muta-tions are reported in the human PrP gene and consist of two groups: (1) point mutations within the coding sequence resulting in amino acid substitutions in PrP or production of a stop codon resulting in expression of a truncated PrP; (2) insertions encoding additional integral copies of an octapeptide repeat present in a tandem array of ﬁ ve copies in the normal protein (octapeptide repeat insertion 
[OPRI]). A suggested notation for these diseases is ‘Inherited prion disease (PrP mutation)’ , for instance: Inherited prion disease (PrP 6 OPRI) or Inherited prion disease (PrP P102L). Brief details of the more commonly seen types are given below, for a more compre-hensive review see Ref.
(47)PRNP  analysis should be considered in

(47)PRNP  analysis should be considered in 
all early-onset dementing or ataxic disorders and is available from the UK National Prion Clinic (see websites).
(a) PrP P102L
This mutation was ﬁ  rst reported in 1989 in a UK and US family 
and has now been demonstrated in many other kindreds world-wide. Progressive ataxia is the dominant clinical feature, with dementia and pyramidal features. However, marked variability 
both at the clinical and neuropathological level is apparent in some families. A family with marked amyotrophic features has also been reported and cases with severe dementia in the absence of promi-nent ataxia are also recognized.
(b) PrP A117V
This mutation has been described in families from France, United States, and UK. The clinical features are pre-senile dementia associ-ated with pyramidal signs, parkinsonism, pseudobulbar features, and cerebellar signs. Parkinsonian features may predominate in the early stages and mimic Parkinson’s disease.
(c) PrP D178N

This mutation was originally described in two Finnish families with a CJD-like phenotype and has since been demonstrated in families in Hungary, the Netherlands, Canada, Finland, France, and the UK. This mutation was also reported in two unrelated families with fatal familial insomnia (FFI).
(48) The ﬁ  rst case described had a 
rapidly progressive disease characterized clinically by untreatable insomnia, dysautonomia and motor signs, and neuropathologically by selective atrophy of the anterior-ventral and medio-dorsal tha-lamic nuclei. Proteinase K treatment of extracted PrP
Sc from FFI 
cases has shown a different sized PrP band on Western blots than PrP
Sc from CJD cases suggesting that FFI may be caused by 
a distinct prion strain type. Goldfarb et al.(49) reported that in all

a distinct prion strain type. Goldfarb et al.(49) reported that in all 
the codon 178 families they studied with a CJD-like disease the codon 178 mutation was encoded on a valine 129 allele while all FFI kindreds encode the same codon 178 mutation on a methionine 129 allele. They suggested that the genotype at codon 129 determines phenotype. Insomnia is not uncommon in CJD patients and FFI and CJD may represent extremes of a spectrum of related disease phenotypes. An inherited case with the E200K 
Fig. 4.1.4.1 Pathogenic mutations (above) and polymorphic variants of the human prion protein gene.4.1.4 prion disease

SECTION 4  clinical syndromes of adult psychiatry 358
mutation, which is normally associated with a CJD-like phenotype, 
has been reported with an FFI phenotype. An Australian family has also been reported with the FFI genotype but in which affected family members have a range of phenotypes encompassing typical CJD, FFI, and an autosomal dominant cerebellar ataxia-like illness.
(d) PrP E200K
This mutation was ﬁ  rst described in families with CJD. Affected

This mutation was ﬁ  rst described in families with CJD. Affected 
individuals develop a rapidly progressive dementia with myoclo-nus and pyramidal, cerebellar or extrapyramidal signs, and a dura-tion of illness usually less than 12 months. In marked contrast to other variants of inherited prion disease, the EEG usually shows the characteristic pseudoperiodic sharp wave activity seen in spo-radic CJD. Interestingly, this mutation accounts for the three reported ethnogeographic clusters of CJD where the local incidence of CJD is around 100-fold higher than elsewhere (amongst Libyan Jews and in regions of Slovakia and Chile).
(50,51) Now that cases

(50,51) Now that cases 
can be diagnosed by PrP gene analysis, atypical forms of this condi-tion are being detected with phenotypes other than that of classical CJD. Of interest also are reports that peripheral neuropathy can occur in this disease. Elderly unaffected carriers of the mutation have been reported. Patients with this condition have now been reported in several other countries outside the well-recognized clusters, including the UK. At least one of the UK cases does not appear to related to the ethnogeographic clusters mentioned above suggesting a separate UK focus for this type of inherited prion disease.
(e) PrP 6 OPRI
This was the ﬁ  rst PrP mutation to be reported and was found in a 
small UK family with familial CJD(9) now known to form part of a

small UK family with familial CJD(9) now known to form part of a 
the largest known kindred with an inherited prion disease caused by an OPRI mutation. The diagnosis in the family had been based on an individual who died in the 1940s with a rapidly progressive illness characteristic of CJD. The reported duration of illness was 6 months. Pathologically there was gross status spongiosis and astrocytosis affecting the entire cerebral cortex, and this case is used to illustrate classic CJD histology in Greenﬁ  eld’s Neuropathology .
However, other family members had a much longer duration GSS-like illness. Histological features were also extremely variable. This observation led to screening of various case of neurodegenerative disease and to the identiﬁ  cation of a case classiﬁ  ed on clinical 
grounds as familial Alzheimer’s disease.
(52) More extensive screen-

ing work identiﬁ  ed further families with the same mutation which 
were then demonstrated by genealogical studies to form part of an extremely large kindred.
(53–55)  Clinical information has been col-

lected on over 80 affected individuals over seven generations. Affected individuals develop in the third to fourth decade onset of a progressive dementia associated with a varying combination of cerebellar ataxia and dysarthria, pyramidal signs, myoclonus and occasionally extrapyramidal signs, chorea and seizures. The demen-tia is often preceded by depression and aggressive behaviour. A number of cases have a long-standing personality disorder,characterized by aggression, irritability, antisocial and criminal activity, and hypersexuality, which may be present from early child-hood, long before overt neurodegenerative disease develops. The histological features vary from those of classical spongiform encephalopathy (with or without PrP amyloid plaques) to cases lacking any speciﬁ  c features of these conditions.

(56) Age at onset in this condition can be predicted according to genotype at polymor-
phic codon 129. Since this pathogenic insertional mutation occurs on a methionine 129 PrP allele, there are two possible codon 129 genotypes for affected individuals, methionine 129 homozygotes or methionine 129/valine 129 heterozygotes. Heterozygotes have an age at onset which is about a decade later than homozygotes.
(53)
Pre-symptomatic and antenatal testing
Direct gene testing allows unequivocal diagnosis in patients with inherited forms of the disease and pre-symptomatic testing of unaffected but at-risk family members, as well as antenatal test-ing.
(57) Because of the effect of PRNP  codon 129 genotype on the

(57) Because of the effect of PRNP  codon 129 genotype on the 
age of onset of disease associated with some mutations it is possible to determine within a family whether a carrier of a mutation will have an early or late onset of disease. Most of the mutations appear to be fully penetrant, however experience with some is extremely limited. In some families, for example with E200K or D178N (fatal familial insomnia), there are examples of elderly unaffected gene carriers who appear to have escaped the disease. Genetic counsel-ling is essential prior to pre-symptomatic testing and follows a pro-tocol similar to that established for Huntington’s disease. A positive PrP gene analysis has important consequences for other family members, and it is preferable to have discussed these issues with others in the immediate family before testing. Following the identi-ﬁ cation of a mutation the wider family should be referred for

genetic counselling. It is vital to counsel both those testing positive for mutations and those untested but at-risk that they should not 
be blood or organ donors and should inform surgeons, including dentists, of their risk status prior to signiﬁ  cant procedures as 
precautions may be necessary to minimize risk of iatrogenic transmission.

While prion diseases can be transmitted to experimental animals by inoculation, it is important to appreciate that they are not con-tagious in humans. Documented case-to-case spread has only occurred by cannibalism (kuru) or following accidental inocula-tion with prions. Such iatrogenic routes include the use of inade-quately sterilized intracerebral electrodes, dura mater, and corneal grafting, and from the use of human cadaveric pituitary-derived growth hormone or gonadotrophin. As discussed above, there is now evidence that vCJD prion infection is transmissible by blood transfusion. UK policy for some time has been to leucodeplete all whole blood and to source plasma for plasma products from out-side the UK. A further possible route of transmission of vCJD is via contaminated surgical and medical instruments. Prions resist conventional sterilization methods and neurosurgical instruments

are known to be able to act as a vector for prion transmission: 
several cases of iatrogenic transmission of sporadic CJD prions via neurosurgical instruments are documented.
(58,59) Recent evidence 
suggests that classical CJD may also be transmitted by other surgi-cal procedures.
(60) The wider tissue distribution of prions in 
vCJD(42) together with the potential that signiﬁ  cant numbers in the 
population may be silently infected has considerably increased these concerns.
Certain occupational groups are at risk of exposure to human 
prions, for instance neurosurgeons and other operating theatre staff, pathologists and morticians, histology technicians, as well as

359
an increasing number of laboratory workers. Because of the pro-
longed incubation periods to prions following administration to sites other than the central nervous system (CNS), which is associ-ated with clinically silent prion replication in the lymphoreticular tissue, treatments inhibiting prion replication in lymphoid organs may represent a viable strategy for rational secondary prophylaxis after accidental exposure. A preliminary suggested regimen is a short course of immunosuppression with oral corticosteroids in individuals with significant accidental exposure to human prions.
(61)
Prognosis and treatment
All recognized prion diseases are invariably fatal following a pro-gressive course.
The duration of illness in sporadic patients is very short with a 
mean duration of 3–4 months. However, in some of the inherited cases the duration can be 20 years or more. However, there have been signiﬁ  cant recent advances in understanding prion propaga-

tion and neurotoxicity and clear proof of principle studies of several therapeutic or secondary prophylactic approaches in ani-mal models suggesting effective therapeutics for human disease is realistic.
(62)
A variety of drugs have been tried in individual or small num-
bers of patients over many years. There is no clear evidence of efﬁ cacy of any agent, and controlled clinical trials are needed. Such

bers of patients over many years. There is no clear evidence of efﬁ cacy of any agent, and controlled clinical trials are needed. Such 
trials are highly challenging. Prion diseases are rare, often rapidly progressive and always fatal which may make randomization to placebo unacceptable. Patterns of disease overall extremely variable with clinical durations varying from weeks to more than 2 years in sporadic CJD, and more than 20 years in some inherited prion dis-eases. As ‘ﬁ  rst generation’ treatments proposed for prion disease 
are likely, at best, to have only a modest effect on disease progres-sion, even using survival duration as an outcome measure requires study of large numbers to reliably assess efﬁ  cacy. There is a lack of

systematic natural history studies of disease progression and an absence of biological markers of disease activity. In the United Kingdom, at the request of the Government’s Chief Medical Ofﬁ  cer, 
a clinical trial protocol (http://www.controlled-trials.com/
ISRCTN06722585/prion1) and infrastructure has been developed to rigorously assess the drug quinacrine
(63) and to provide a 
framework for assessment of novel therapeutics as these become available: the MRC PRION-1 trial. Importantly under these cir-cumstances, a formal consultation with patient’s representatives was organized to reﬁ  ne the protocol so that it would be acceptable 
to the majority of potential participants http://www.mrc.ac.uk/prn/pdf-cjd_workshop.pdf). Pentosan polyphosphate is another candidate anti-prion drug and has shown some efﬁ  cacy in animal

to the majority of potential participants http://www.mrc.ac.uk/prn/pdf-cjd_workshop.pdf). Pentosan polyphosphate is another candidate anti-prion drug and has shown some efﬁ  cacy in animal 
models. Unlike quinacrine, it does not enter the CNS readily and has been administered by intraventricular infusion in several patients. Major toxicity has been reported by this route in animal studies and such treatment was not supported by the UK’s Committee of Safety on Medicines or CJD Therapy Advisory Group. A report summarizing clinical experience to date with this 
treatment has been produced (http://www.mrc.ac.uk/Utilities/
Documentrecord/index.htm?d=MRC003453).
While the precise molecular events in prion propagation are not 
clear, it is clear that PrP
C is the essential substrate. Interference with 
PrPC expression in adult brain is without serious effect and blocks

PrPC expression in adult brain is without serious effect and blocks 
onset of neurological disease in animal models.(61) It should be possible to identify small molecules, which penetrate the CNS
to bind to PrPC and to prevent its recruitment into prions, or to
use one of a number of emerging technologies to reduce PrPC

expression in brain. If such methods are able to reduce prionpropagation rates to below those of natural clearance mechanisms it ought to be possible to cure prion infection. New methods for early diagnosis—and their timely use—will be crucial, as such methods will not reverse neuronal cell loss which is appreciableor severe by the time clinical diagnosis is typically reached. Proofof principle studies in animal models suggest that humanizedanti-PrP monoclonal antibodies could be used for passive immuni-zation in the early pathogenesis to block neuroinvasion. Thistreatment could be considered for known iatrogenically infected individuals.
(64)
UK National Prion Clinic, National Hospital for Neurology and 
Neurosurgery, London, http://www.nationalprionclinic.org
Medical Research Council Prion Unit, Institute of Neurology, London,

Medical Research Council Prion Unit, Institute of Neurology, London, 
http://www.prion.ucl.ac.uk/
UK CJD Surveillance Unit, Western General Hospital, Edinburgh, http:
//www.cjd.ed.ac.uk/
UK Department of Health, http://www.dh.gov.uk/PolicyAndGuidance/
HealthAndSocialCareT opics/CJD/fs/en
CJD Support Network, http://www.cjdsupport.net/
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4.1.5 Dementia with Lewy bodies
Lewy bodies are spherical neuronal inclusions, ﬁ  rst described by 
the German neuropathologist Friederich Lewy while working in Alzheimer’s laboratory in Munich in 1912. In 1961, Okazaki pub-lished case reports about two elderly men who presented with dementia and died shortly after with severe extrapyramidal rigidity. Autopsy showed Lewy bodies in their cerebral cortex.
(1) Over

(1) Over 
the next 20 years, 34 similar cases were reported, all by Japanese workers. Lewy body disease was thus considered to be a rare cause of dementia, until a series of studies in Europe and North America, in the late 1980s, identiﬁ  ed Lewy bodies in the brains of between 
15 and 20 per cent of elderly demented cases reaching autopsy.
(2,3)
Dementia with Lewy bodies (DLB) is unlikely to be a newly occur-ring disorder, since re-examination of autopsy material collected from elderly demented patients in Newcastle during the 1960s, reveals cortical Lewy bodies in 17 per cent of cases. The recent recognition of DLB as the second most common form of degenera-tive dementia in old age is largely due to the widespread use of improved neuropathological techniques, initially antiubiquitin immunocytochemistry, and more recently speciﬁ  c staining for 
alpha-synuclein which is a core constituent of Lewy bodies and related lesions.
The spectrum of Lewy body disease

The presence of Lewy bodies probably indicates neuronal dysfunc-tion which is usually indicative of neurological disease. The clinical presentation varies according to the site of Lewy body formation and associated neuronal loss. Three main clinicopathological syn-dromes have been described.
X Parkinson’s disease, an extrapyramidal movement disorder—
associated with degeneration of subcortical neurones, particu-larly in substantia nigra.X Dementia with Lewy bodies, a dementing disorder with promi-
nent neuropsychiatric features—associated with degeneration of cortical neurones, particularly in frontal, anterior cingulate, insular, and temporal regions.
X Autonomic failure with syncope and orthostatic hypotension—
associated with degeneration of sympathetic neurones in spinal cord.
In clinical practice, elderly patients often have heterogenous

In clinical practice, elderly patients often have heterogenous 
combinations of parkinsonism, dementia, and autonomic failure, reﬂ ecting pathological involvement at multiple locations.
Dementia is usually, but not always, the presenting feature of DLB. 
A minority of patients present with parkinsonism alone, some with psychiatric disorder in the absence of dementia, and others with orthostatic hypotension, falls, or transient disturbances of consciousness. Episodes of confusion, progressive cognitive decline, and dementia follow in due course. Fluctuation in cognitive performance and functional abilities, which is based in variations in attention and level of consciousness, is the most characteristic feature of DLB and the one which causes greatest diagnostic difﬁ culties. It is usually evident on a day-to-day basis, and often

apparent within much shorter periods. The marked amplitude between best and worst performance distinguishes it from the minor day-to-day variations that commonly occur in dementia of any aetiology. Transient disturbances of consciousness, in which patients are found mute and unresponsive for periods of several 
minutes, may represent the extreme of ﬂ  uctuation in attention 
and arousal and are often mistaken for transient ischaemic attacks despite a lack of focal neurological signs. Repeated visual hallucina-tions are present in about two-thirds of patients. They take the form of vivid, colourful, and sometimes fragmented ﬁ  gures of

people and animals, which are usually described in great detail. Emotional responses vary from intense fear to indifference or even amusement. Although patients may respond to their hallucinations, for example, trying to feed an imaginary dog, they later often have good insight into their unreality. Others develop elaborate system-atized delusions, usually persecutory or of a phantom boarder. Auditory hallucinations are much less frequent, and only a minor-ity of patients have olfactory or tactile experiences. Depressive symptoms are common and about 40 per cent of patients will have a major depressive episode, similar to the rate in Parkinson’s disease and signiﬁ  cantly greater than in Alzheimer’s disease (AD). 
The frequency and severity of spontaneous motor features of parkinsonism varies from one clinical setting to another due to referral biases. Postural instability and gait difﬁ  culty are the most

The frequency and severity of spontaneous motor features of parkinsonism varies from one clinical setting to another due to referral biases. Postural instability and gait difﬁ  culty are the most 
common manifestations, tremor dominant symptoms occurring in only 20 per cent or less.
(4) Less than half of DLB cases have parkin-
sonism at presentation and a quarter continue to have no evidence at any point in their illness. Clinicians must therefore be prepared to make the diagnosis of DLB in the absence of extrapyramidal motor features. If they do not, their case detection rates will be unacceptably low. Severe neuroleptic sensitivity reactions can precipitate irreversible parkinsonism, further impair consciousness level, and induce autonomic disturbances reminiscent of neurolep-tic malignant syndrome. They occur in 40 to 50 per cent of neuro-leptic-treated DLB cases and are associated with a two- to threefold 4.1.5 dementia with lewy bodies

SECTION 4  clinical syndromes of adult psychiatry 362
increased mortality.(5) Acute D2 receptor blockade is thought to 
mediate these effects; and, despite initial reports, atypical antipsy-chotics seem to be as likely to cause neuroleptic sensitivity reactions as older drugs.
(6) Sleep disorders have more recently been recog-
nized as common in DLB with daytime somnolence and rapid eye 
movement sleep behaviour disorder as prodromal features.(7)
Recurrent falls and syncope occur in up to a third of DLB cases, 
reﬂ ecting autonomic nervous system involvement which may also 
be evident as early urinary incontinence, constipation, and sexual dysfunction.
Pathological classiﬁ  cation
Lewy bodies are composed of intermediate neuroﬁ  lament proteins,

Lewy bodies are composed of intermediate neuroﬁ  lament proteins, 
which are abnormally truncated and phosphorylated. Their pres-ence indicates that a neurone is attempting to eliminate damaged proteins from its cytoplasm, a process which is usually followed by cell death. Ubiquitin, α-synuclein, α- and β-crystalin, and associ-
ated enzymes are the main chemical constituents. Subcortical Lewy bodies have a dense hyaline core surrounded by a halo of radiating ﬁ laments, and are easily seen with conventional histopathological 
techniques. Cortical Lewy bodies are more easily visualized using antiubiquitin staining but this lacks speciﬁ  city and immunohisto-
chemical staining for alpha-synuclein, is now the most sensitive and speciﬁ  c method currently available for detecting Lewy bodies

chemical staining for alpha-synuclein, is now the most sensitive and speciﬁ  c method currently available for detecting Lewy bodies 
and Lewy-related pathology. Current thinking is that Lewy bodies form within neurones as a cytoprotective response in an attempt 
to sequester toxic alpha-synuclein oligomers. Widely distributed aggregates of alpha-synuclein (Lewy neurites) probably represent 
an earlier stage in the neurodegenerative process than Lewy body formation itself. Lewy neurites are seen in the substantia nigra, hippocampal region CA2/3, dorsal vagal nucleus, basal nucleus of Meynert, and transentorhinal cortex. Ubiquitin immunocyto-chemistry and α-synuclein-speciﬁ  c monoclonal antibody stains

are beginning to reveal the extensive nature of these neuritic changes, which are probably more relevant for symptom formation than the relatively sparsely distributed Lewy bodies. The presence of Lewy neurites in presynaptic terminals is thought to have a par-ticularly severe impact on synaptic function.
(8)
Recommendations have been made(9) about which brain regions 
to examine for the presence of Lewy bodies and Lewy neurites and a simple semi-quantitative scoring system devised. These scores are added to generate three pathological categories:
1 Brainstem-predominant DLB: predilection sites are substantia 
nigra, locus coeruleus, and dorsal nucleus of vagus.
2 Limbic (or transitional) DLB: predilection sites are anterior 
cingulate and transtentorhinal cortex.
3 Neocortical DLB: predilection sites are frontal, temporal, and 
parietal cortex.
Of DLB cases presenting via psychiatric clinics, 69 per cent 
have extensive neocortical Lewy body pathology,
(10) but this is not

(10) but this is not 
essential for the development of dementia or other psychiatric symptoms, both of which may occur in the presence of disease limited to limbic structures (24 per cent of cases) or the brainstem 
(7 per cent).
Interpretation of the signiﬁ  cance of coexistent Alzheimer-type 
pathology is a major issue in the pathological assessment of DLB cases. High senile plaque counts are found in 80 to 90 per cent of DLB cases, diffuse and neuritic β-amyloid plaques occurring in sim-
ilar proportions as in pure AD. Signiﬁ  cant tau pathology is absent, 
however, in 80 to 90 per cent whether measured biochemically or by 
counting neocortical neuroﬁ  brillary tangles. Most DLB cases are 
therefore classiﬁ  ed as ‘the Lewy body variant of AD’
(2) if AD is 
deﬁ ned by increased plaque density. Conversely, if AD is deﬁ  ned by

(2) if AD is 
deﬁ ned by increased plaque density. Conversely, if AD is deﬁ  ned by 
frequent neocortical neuroﬁ  brillary tangles, equivalent to Braak 
stages 5 and 6, then 85 to 90 per cent of DLB cases will not fulﬁ  l such 
criteria.(11) (The pathological classiﬁ  cation of AD is also d iscussed in 
Chapter 4.1.2.) The most recent rev ision of pathologi cal diagnostic 
criteria for DLB suggests that both Lewy and Alzheimer pathologies should be fully reported. A probability matrix (see Table 4.1.5.1) is then used to predict the likelihood of the patient having presented with a DLB clinical syndrome, this being directly related to the severity of Lewy-related pathology, and inversely related to the severity of concurrent AD-type pathology.
(9) Minor vascular pathol-
ogy is additionally present in 30 per cent of DLB cases(10) and this is 
also likely to impact upon the clinical manifestations.
The relationship between DLB and

The relationship between DLB and 
Parkinson’s disease dementia
There has been extended debate about the classiﬁ  cation of patients 
who present with motor symptoms of Parkinson’s disease and later develop the typical features of DLB, sometimes after many years of severe motor disability. This is a common outcome reported in up to 78 per cent of PD patients followed over an 8-year period. No major differences between DLB and Parkinson’s disease dementia have been found in any variable examined including cog-nitive proﬁ  le, neuropsychiatric features, sleep disorders, autonomic

dysfunction, type and severity of parkinsonism, neuroleptic sensi-tivity, and responsiveness to cholinesterase inhibitors. It has been suggested that DLB should be diagnosed when dementia occurs before or concurrently with parkinsonism and Parkinson’s disease dementia should be used to describe dementia that occurs in the context of well-established Parkinson’s disease.
(9,12)  This distinc-
tion between DLB and Parkinson’s disease dementia has two dis-tinct clinical phenotypes, based solely on the temporal sequence of appearance of symptoms that has been criticized by those who regard the different clinical presentations as simply representing Table 4.1.5.1  Pathological criteria for DLB taking into account the 
relative contributions of Lewy body and Alzheimer type pathology 
as predictors of a probable DLB clinical presentation–high, 
intermediate, or low probability.
Alzheimer type pathology
NIA–Reagan 
Low (Braak 
stage 0-II)NIA–Reagan
Intermediate(Braak 
stage III-IV)NIA–Reagan

Low (Braak 
High(Braak 
stage V-VI)Lewy Body type 
pathologyBrainstem-predominantLow Low Low
Limbic 
(transitional)High Intermediate Low
Diffuse neocortical High High Intermediate

363
different points on a common spectrum of LB disease, itself under-
pinned by abnormalities in alpha-synuclein metabolism.
The neurobiological basis of dementia in Parkinson’s disease is 
discussed in detail in Chapter 4.1.6.
Clinical diagnosis of DLB
Patients with DLB may present to psychiatric services (cognitive impairment, psychosis, or behavioural disturbance), internal medi-cine (acute confusional states or syncope), or neurology (movement disorder or disturbed consciousness). The details of clinical assess-ment and differential diagnoses will, to a large extent, be shaped by these symptom and specialty biases. In all cases, a detailed history from the patient and reliable informants should document the time of onset of relevant key symptoms, the nature of their progression, and their effects on social, occupational, and personal function.
The recent consensus criteria for the clinical diagnosis of DLB

The recent consensus criteria for the clinical diagnosis of DLB 
are shown in Table 4.1.5.2. Particular emphasis needs to be given to recognizing the characteristic dementia syndrome. Attentional deﬁ cits and prominent frontosubcortical and visuo-perceptual dys-
function are the main features—symptoms of persistent or promi-nent memory impairment are not always present early in the course 
of illness, although they are likely to develop in most patients with 
disease progression. Patients with DLB perform better than Alzheimer’s disease on tests of verbal recall, but relatively worse on 
tests of copying and drawing. With the progression of dementia, the selective pattern of cognitive deﬁ  cits may be lost, making dif-
ferential diagnosis based on clinical examination difﬁ  cult during 
the later stages.
It is the evaluation of ﬂ  uctuation which causes greatest difﬁ  culty 
in clinical practice.
(13) Questions such as, ‘are there episodes when

(13) Questions such as, ‘are there episodes when 
his/her thinking seems quite clear and then becomes muddled?’ were previously suggested as useful probes, but two recent studies found 75 per cent of both AD and DLB carers to respond positively.
(14,15)  More detailed questioning and qualitative analysis 
of carers’ replies is therefore needed. The Clinician Assessment of Fluctuation Scale
(16) requires an experienced clinician to judge 
the severity and frequency of ‘ﬂ  uctuating confusion’ or ‘impaired 
consciousness’ over the previous month. The semi-structured One Day Fluctuation Assessment Scale
(16) can be administered by less 
experienced raters and generates a cut-off score to distinguish DLB from AD or VaD. The Mayo Fluctuations Composite Scale
(15)

(15)
requires three or more ‘yes’ responses from caregivers to structured questions about the presence of daytime drowsiness and lethargy, daytime sleep >2 h, staring into space for long periods or episodes of disorganized speech, as suggestive of DLB rather than AD. Recording variations in attentional performance using a computer-based test system offers an independent method of measuring ﬂ  uctuation, 
which is also sensitive to drug treatment effects.
(17) The assessment 
of extrapyramidal motor features may be complicated by the pres-ence of cognitive impairment. A simple, ﬁ  ve-item subscale of the 
Uniﬁ  ed PD Rating Scale
(18) contains only those items that can reli-

ably be assessed in DLB independent of severity of dementia (tremor at rest, action tremor, body bradykinesia, facial expression, rigidity). Standardized methods of assessing visual hallucinations and other 
visual pathologies in DLB are under development.
(19)
(a) Consensus criteria for DLB
Probable DLB can be diagnosed (Table 4.1.5.2) if any two of the three core features (ﬂ  uctuation, visual hallucinations, spontaneous Table 4.1.5.2  Consensus criteria for the clinical diagnosis of probable 
and possible dementia with Lewy bodies (DLB) (Reproduced from 
McKeith I., Dickson, D., Emre, M., et al. Dementia with Lewy bodies, 
3rd report of the dementia consortium, Neurology , 65, 1863–72, 
copyright 2005, AAN Enterprises, Inc.)
1 Central feature  (essential for a diagnosis of possible or probable DLB )
   Dementia deﬁ  ned as progressive cognitive decline of sufﬁ  cient magnitude

   Dementia deﬁ  ned as progressive cognitive decline of sufﬁ  cient magnitude 
to interfere with normal social or occupational function. Prominent or persistent memory impairment may not necessarily occur in the early 
stages but is usually evident with progression. Deﬁ  cits on tests of attention, 
executive function and visuo-spatial ability may be especially prominent.
2  Core features  (two core features are sufﬁ  cient for a diagnosis of probable 
DLB, one for possible DLB)
 Fluctuating cognition with pronounced variations in attention and alertness
  Recurrent visual hallucinations that are typically well formed and detailed  Spontaneous features of parkinsonism
3  Suggestive features  (if one or more of these is present in the presence of

Recurrent visual hallucinations that are typically well formed and detailed  Spontaneous features of parkinsonism
3  Suggestive features  (if one or more of these is present in the presence of 
one or more core features, a diagnosis of probable DLB can be made. In the absence of any core features, one or more suggestive features is sufﬁ  cient 
for possible DLB. Probable DLB should not be diagnosed on the basis of 
suggestive features alone)
   REM sleep behaviour disorder
   Severe neuroleptic sensitivity
   Low dopamine transporter uptake in basal ganglia demonstrated by SPECT 
or PET imaging
4  Supportive features  (commonly present but not proven to have diagnostic 
speciﬁ  city)
 Repeated falls and syncope
 Transient, unexplained loss of consciousness  Severe autonomic dysfunction e.g. orthostatic hypotension, urinary 
incontinence
 Hallucinations in other modalities
 Systematized delusions
 Depression Relative preservation of medial temporal lobe structures on CT/MRI scan

  Generalised low uptake on SPECT/PET perfusion scan with reduced 
occipital activity
 Abnormal (low uptake) MIBG myocardial scintigraphy
 Prominent slow wave activity on EEG with temporal lobe transient sharp waves
5 A diagnosis of DLB is less likely
  In the presence of cerebrovascular disease evident as focal neurological 
signs or on brain imaging
  In the presence of any other physical illness or brain disorder sufﬁ  cient to 
account in part or in total for the clinical picture
 If parkinsonism only appears for the ﬁ  rst time at a stage of severe dementia
6 Temporal sequence of symptoms
  DLB should be diagnosed when dementia occurs before or concurrently 
with parkinsonism (if it is present). The term Parkinson’s disease dementia

with parkinsonism (if it is present). The term Parkinson’s disease dementia 
(PDD) should be used to describe dementia that occurs in the context of well-established Parkinson’s disease. In a practice setting the term that 
is most appropriate to the clinical situation should be used and generic 
terms such as LB disease are often helpful. In research studies in which 
distinction needs to be made between DLB and PDD, the existing one-year 
rule between the onset of dementia and parkinsonism DLB continues to be recommended. Adoption of other time periods will simply confound 
data pooling or comparison between studies. In other research settings 
that may include clinico-pathologic studies and clinical trials, both clinical phenotypes may be considered collectively under categories such as LB 
disease or alpha-synucleinopathy.4.1.5 dementia with lewy bodies

SECTION 4  clinical syndromes of adult psychiatry 364
motor features of parkinsonism) are present. Probable DLB can 
also be diagnosed if one core feature is accompanied by one or more suggestive features (REM sleep behaviour disorder, severe neuroleptic sensitivity, low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging). Possible DLB can be diagnosed if there is one core feature alone or one or more suggestive features in the absence of any core features. Suggestive features are not in the light of current knowledge considered sufﬁ  -
cient, even in combination, to warrant a diagnosis of probable DLB in the absence of any core feature.
There are four main categories of disorder that should be consid-ered in the differential diagnosis of DLB (Table 4.1.5.3).
(a) Other causes of dementia
Of autopsy-conﬁ  rmed DLB cases, 65 per cent meet the NINCDS-
ADRDA clinical criteria for probable or possible AD,(20) and this is

ADRDA clinical criteria for probable or possible AD,(20) and this is 
the most frequent clinical misdiagnosis of DLB patients presenting with a primary dementia syndrome. This suggests DLB should routinely be excluded when making the diagnosis of AD. Up to 
one-third of DLB cases are additionally misclassiﬁ  ed as vascular 
dementia by virtue of items such as the ﬂ  uctuating nature and 
course of illness. Pyramidal and focal neurological signs are, how-ever, usually absent. The development of myoclonus in patients with a rapidly progressive form of DLB may lead the clinician to suspect Creutzfeldt–Jakob disease.
(b) Other causes of delirium
In patients with intermittent delirium, appropriate examination and laboratory tests should be performed during the acute phase to maximize the chances of detecting infective, metabolic, inﬂ  amma-

tory, or other aetiological factors. Pharmacological causes are par-ticularly common in elderly patients. Although the presence of any of these features makes a diagnosis of DLB less likely, comorbidity is not unusual in elderly patients and the diagnosis should not be excluded simply on this basis.(c) Other neurological syndromes
In patients with a prior diagnosis of Parkinson’s disease, the onset of visual hallucinations and ﬂ  uctuating cognitive impairment may

In patients with a prior diagnosis of Parkinson’s disease, the onset of visual hallucinations and ﬂ  uctuating cognitive impairment may 
be attributed to side-effects of antiparkinsonian medications, and this must be tested by dose reduction or withdrawal. Other atypical parkinsonian syndromes associated with poor levodopa response, cognitive impairment, and postural instability include progressive supranuclear palsy and multi-system atrophy. Syncopal episodes in DLB are often incorrectly attributed to transient ischaemic attacks, despite an absence of focal neurological signs. Recurrent disturbances in consciousness accompanied by complex visual hallucinations may suggest complex partial seizures (temporal lobe epilepsy), and vivid dreaming with violent movements during sleep may meet criteria for REM sleep behaviour disorder. Both these conditions have been reported as uncommon presenting symp-toms of autopsy-conﬁ  rmed DLB.
(21,22)
(d) Late-onset functional psychiatric disorder

(21,22)
DLB should be considered if a patient spontaneously develops 
parkinsonian features or cognitive decline (or shows excessive sensitivity to neuroleptic medication) in the course of late-onset delusional disorder, depressive psychosis, or mania.
(21)
Laboratory investigations including neuroimaging
Systemic and pharmacological causes of delirium need to be excluded. The standard EEG may show early slowing, epoch by epoch ﬂ  uctuation, and transient temporal slow wave activity.
(23)
There are as yet no clinically applicable genotypic or CSF markers 
to support a DLB diagnosis.(24) There are, however, sufﬁ  cient stud-
ies to conclude that neuroimaging investigations may be helpful in supporting the clinical diagnosis. Changes associated with DLB include preservation of hippocampal and medial temporal lobe volume on MRI
(25,26) and occipital hypo-perfusion on SPECT.(27)

Other features such as generalized atrophy, white matter chang-es,
(28) and rates of progression of whole brain atrophy(29) appear to 
be unhelpful in differential diagnosis. Dopamine transporter loss in the caudate and putamen, a marker of nigro-striatal degenera-tion can be detected by pre-synaptic dopaminergic SPECT. Preliminary studies suggesting high speciﬁ  city and sensitivity for 
predicting clinical
(30) and pathological diagnoses of DLB have been 
conﬁ  rmed in a large multi-centre trial which found 78 per cent 
sensitivity and 90 per cent speciﬁ  city for identifying probable 
DLB versus non-DLB dementia.(31) Diagnostic sensitivity based 
upon the presence of the three core clinical features alone has been estimated at below 50 per cent and speciﬁ  city at >90 per cent which 
suggests that dopaminergic imaging is most useful when signiﬁ  -
cant clinical diagnostic uncertainty exists.

In population-based clinical studies, prevalences of around 0.7 per cent for DLB in the 65+ age group have been reported suggesting that it could account for up to 10 per cent of all dementia cases, a 
ﬁ gure consistent with DLB rates of 10–15 per cent from hospital-
based autopsy series. A recent community study of 85+ year olds 
found 5.0 per cent to meet consensus criteria for DLB (3.3 per cent probable, 1.7 per cent possible) representing 22 per cent of all demented cases,
(32) similar to other clinical estimates and consis-
tent with estimates of Lewy body prevalence in a dementia case Table 4.1.5.3  Conditions to be considered in the differential 
diagnosis of dementia with Lewy bodies
Other causes of dementia
Vascular dementia
Creutzfeldt–Jakob disease
Other causes of delirium
Infective/pharmacological/metabolic/inﬂ  ammatory

Other neurological syndromes
Parkinson’s diseaseProgressive supranuclear palsy (Steele–Richardson–Olszewski syndrome)
Multisystem atrophy
Corticobasal degenerationRapid eye movement sleep behaviour disorder (RBD)
Recurrent syncope/unexplained falls
Transient disturbances of consciousness
Comlex partial seizures
Late-onset psychiatric disorders
Delusional disorder (late paraphrenia/late-onset schizophrenia)Depressive psychosis

365
register followed to autopsy.(33) One population-based, autopsy 
study found Lewy bodies to be evenly distributed between the demented and the non-demented, and this may be interpreted as evidence of a substantial pool of pre-clinical cases.
(34) Classical epi-
demiological studies to determine age and sex variation and poten-tial risk factors for DLB have not yet been reported.
Genetics
It is clear from several case studies that familial cases of DLB occur
(35,36) and that Lewy bodies are commonly seen in familial 
cases of Alzheimer’s disease.(37) There are recent reports that 
triplication of the alpha-synuclein gene (SNCA) can cause DLB, Parkinson’s disease, and Parkinson’s disease dementia whereas gene duplication is associated only with motor Parkinson’s disease sug-gesting a gene dose effect.
(38) However, SCNA multiplication is not 
found in most Lewy body disease patients.
Course and prognosis

Rate of cognitive decline in DLB is generally reported as similar to Alzheimer’s disease
(39) and survival from onset to death is reduced 
with self-reports of depression and the presence of extrapyramidal signs as important adverse predictors.
(40) The end stage is typically 
one of profound dementia and parkinsonism. Even in the early stages, personal and social function and performance in daily living skills may be markedly impaired by a combination of cognitive, psychiatric, and neurological disability to a degree signiﬁ  cantly greater than in 
patients with Alzheimer’s disease and comparable mental test scores.
(41) Psychotic symptoms, particularly visual hallucinations, 
tend to be very persistent throughout the whole course of illness. There have been three overlapping stages of the illness described.
(21)
The ﬁ  rst stage is often recognized only in retrospect, and may

(21)
The ﬁ  rst stage is often recognized only in retrospect, and may 
extend back 1 to 3 years’ prepresentation with occasional minor episodes of forgetfulness, sometimes described as lapses of concen-tration or ‘switching off’ . A brief period of delirium is sometimes noted for the ﬁ  rst time, often associated with genuine physical ill-
ness and/or surgical procedures. Disturbed sleep, nightmares, and daytime drowsiness often persist after recovery.
Progression to the second stage frequently prompts psychiatric 
or medical referral. A more sustained cognitive impairment is established, albeit with marked ﬂ  uctuations in severity. Recurrent 
confusional episodes are accompanied by vivid hallucinatory experiences, visual misidentiﬁ  cation syndromes, and topographical 
disorientation. Extensive medical screening is usually negative. Attentional deﬁ  cits are apparent as apathy, and daytime somno-
lence and sleep behaviour disorder
(17) may be severe. Gait disorder

(17) may be severe. Gait disorder 
and bradykinesia are often overlooked, particularly in elderly subjects. Frequent falls occur due to either postural instability or syncope.
The third and ﬁ  nal stage often begins with a sudden increase in 
behavioural disturbance, leading to requests for sedation or hospi-tal admission by perplexed and exhausted carers. The natural course from this point is variable and obscured by the high inci-dence of adverse reactions to neuroleptic medication. For patients not receiving, or not tolerating, neuroleptics a progressive decline 
into severe dementia with dysphasia and dyspraxia occurs over

into severe dementia with dysphasia and dyspraxia occurs over 
months or years, with death usually due to cardiac or pulmonary disease. During this terminal phase patients show continuing behavioural disturbance including vocal and motor responses to hallucinatory phenomena. Lucid intervals with some retention of 
recent memory function and insight may still be apparent. Neurological disability is often profound, with ﬁ  xed ﬂ  exion defor-
mities of the neck and trunk and severe gait impairment. Parkinsonian signs and paraplegia in ﬂ  exion may also occur in 
advanced AD and other dementias. Parkinsonism occurring for the ﬁ rst time late in the course of a dementia is therefore consistent 
with a diagnosis of DLB, but not speciﬁ  c for it.
Advice about management
Patient management in DLB is complex and includes: early

Patient management in DLB is complex and includes: early 
detection, investigation, diagnosis, and treatment of cognitive impairment; assessment and management of neuropsychiatric and behavioural symptoms; treatment of the movement disorder and monitoring and management of autonomic dysfunction, and sleep disorders. The evidence base for making recommendations about the management of DLB is limited and what follows is based upon consensus opinion of clinicians experienced in treating DLB.
(9)
The most important practice point in the management of a patient with DLB is caution in (or preferably avoidance of) the use of neuroleptic medications, which are the mainstay of antipsychotic treatment in other patient groups. Severe neuroleptic sensitivity reactions
(5,6) can precipitate irreversible parkinsonism, further

(5,6) can precipitate irreversible parkinsonism, further 
impair consciousness level, and induce autonomic disturbances reminiscent of neuroleptic malignant syndrome. They occur in 40 to 50 per cent of neuroleptic-treated DLB cases and are associ-ated with a two- to threefold increased mortality. Acute D
2 receptor 
blockade is thought to mediate these effects; and despite initial reports, atypical antipsychotics seem to be as likely to cause neuro-leptic sensitivity reactions as older drugs. A scheme for the management of the neuropsychiatric symptoms of DLB is suggested in Fig. 4.1.5.1.
Until safe and effective medications become available, there is no 
doubt that the mainstay of clinical management is to educate patients and carers about the nature of their symptoms and to suggest coping strategies. The clinician must ascertain which symp-toms are most troublesome for the sufferer and explain the risks and beneﬁ  ts associated with changes in medication. In these cir-

cumstances where the clinician is walking a therapeutic tightrope between parkinsonism and psychosis, the best outcome is invari-
ably a compromise between a relatively mobile but psychotic 
patient and a non-psychotic but immobile individual. The patient and his carers may only be able to decide which is the lesser of these evils after experiencing both states.
Non-pharmacological interventions
Non-pharmacological interventions have the potential to amelio-rate many of the symptoms and functional impairments associated with DLB, but none have yet been systematically evaluated. Cognitive dysfunction and associated symptoms such as VH can for example, be exacerbated by low levels of arousal and attention and strategies to increase these by social interaction and environ-mental novelty may reduce their presence and impact.
Pharmacological treatments
Pharmacological treatment strategies are based upon our knowl-edge of the neurochemical deﬁ  cits underlying speciﬁ  c symptoms

Pharmacological treatment strategies are based upon our knowl-edge of the neurochemical deﬁ  cits underlying speciﬁ  c symptoms 
in DLB. The most clearly established is a correlation between4.1.5 dementia with lewy bodies

SECTION 4  clinical syndromes of adult psychiatry 366
substantia nigra neurone loss and severity of parkinsonism. 
Levodopa responsiveness is less predictable in DLB than in Parkinson’s disease. Activity of the cholinergic enzyme choline 
acetyltransferase is lower in DLB than AD, particularly in temporal 
and parietal cortex.
(42) Clouding of consciousness, confusion, and 
visual hallucinations are recognized effects of anticholinergic drug toxicity, and the summative effects of subcortical and cortical cho-linergic dysfunction probably play a major role in the spontaneous generation of similar ﬂ  uctuating symptoms in DLB. Reductions in 
choline acetyltransferase activity are correlated with the severity of cognitive impairment, and hallucinations may be related to hypo-cholinergic and (relatively) hypermonoaminergic neocortical neu-rotransmitter function.
Levodopa can be used for the motor disorder of both DLB and 
PDD.
(43,44)  Medication should generally be introduced at low

PDD.
(43,44)  Medication should generally be introduced at low 
doses and increased slowly to the minimum required to mini-mize disability without exacerbating psychiatric symptoms. Anticholinergics should be avoided. Visual hallucinations are the most commonly experienced psychiatric symptom and are often accompanied by delusions, anxiety and behavioural disturbance. When pharmacological intervention is required the options 
include cholinesterase inhibitors or atypical antipsychotic medi-cations. Open label studies have demonstrated the effectiveness of 
all three generally available cholinesterase inhibitors in DLB but 
placebo controlled trial data is only available to date for rivastig-mine.
(45) The reported reduction in symptom frequency and

(45) The reported reduction in symptom frequency and 
intensity of VH appears to be mediated at least in part by improved attentional function and the presence of VH is associated with greater cognitive improvement. Cholinesterase inhibitors also improve cognitive impairment with an effect size that is generally larger than seen with the same drugs when used in AD.
(46) There is 
a risk of symptom of rebound on sudden withdrawal,(47) limited 
data on long term effects,(48) and none about possible disease 
modifying effects.
Side effects of cholinesterase inhibitors in DLB include hyper-
salivation, lacrimation, and urinary frequency, in addition to the usual gastro-intestinal symptoms and a dose dependent exacerba-tion of extrapyramidal motor features may occur in a minority.
(49)

(49)
There is no evidence that any one cholinesterase inhibitor is better 
than others.(50) If they are ineffective or if more acute symptom Fig. 4.1.5.1 Management of the neuropsychiatric symptoms of DLB.If psychotic symptoms persist despite the reduction or withdrawal of unwanted medications a
cholinesterase inhibitor should be gradually introduced in standard dose. Improvements aregenerally seen within the first few weeks and rapid relapse may occur if the drug is stoppedabruptly. CHOLINESTERASE INHIBITOR TRIAL
If psychotic symptoms still persist a cautious trial of an antipsychotic may be justified as long as
the patient and carer understand the potential risks of severe adverse side-effects.  Since most

neuroleptic sensitivity reactions occur during the first 2 weeks of treatment, it may be wise to
admit patients into hospital during initiation of neuroleptic therapy.  Since side-effects are dose
related, treatment should start with the lowest possible dose and slow titration.  Approximately
50% of patients are expected to tolerate medication.
NEUROLEPTIC TRIAL—VERY LOW DOSE AND SLOW TITRATION
Neuroleptics should be discontinued if parkinsonism appears for the first time in a DLB patient,
and the dose substantially reduced or stopped in patients whose pre-existing parkinsonismworsens. Severe neuroleptic sensitivity reactions should be treated as a medical emergencysimilar to neuroleptic malignant syndrome.
STOP IF NEUROLEPTIC SENSITIVITY IS SUSPECTED

Other psychotropic medications may offer short-term benefits.  Clonazepam can help nocturnal
hallucinations and behavioural disturbance. SSRIs and SRNIs may improve mood disorders.
CONSIDER ALTERNATIVE MEDICATIONSExplain hallucinations, delusions, and other neuropsychiatric symptoms of DLB to patient and
carer as an intrinsic part of the disorder. EDUCATION
Establish the nature and extent of cognitive impairment, neuropsychiatric features, sleep disorder,
autonomic dysfunction and motor parkinsonism by interview with patient and carer.Determine the extent to which of these impairs quality of life and requires active treatment.Record pretreatment scores for each using appropriate rating scales.
BASELINE ASSESSMENT
Gradually reduce, and if possible stop, antiparkinsonian medications in the following order :
anticholinergicsL-deprenylamantadinedirect  dopamine agonistsCOMT inhibitorslevodopa

Gradually reduce, and if possible stop other anticholinergics, sedatives and drugs which may
exacerbate confusional symptoms. REDUCE ANTI-PARKINSONIAN MEDICATIONS
After each drug change, repeat measures in all relevant symptom domains to monitor for
beneficial or adverse responses. MONITOR RESPONSE

367
control of behaviour is required, it may be difﬁ  cult to avoid a cau-
tious trial of an atypical antipsychotic. The clinician should warn both the carer and patient of the possibility of a severe sensitivity reaction.
(5) Second generation atypicals with potentially more 
favourable pharmacological properties, such as quetiapine, clozap-
ine, and aripiprazole may have theoretical advantages over tradi-tional agents in LB disease but controlled clinical trial data is lack-ing and clinicians should remain vigilant to the possibility of adverse side effects.
Depression is common in DLB and there have been no system-

atic studies of its management. At the present time SSRI and SNRIs are probably preferred pharmacological treatment. Tricylic antide-pressants and those with anticholinergic properties should gener-ally be avoided. Apathy is also common and may improve with cholinesterase inhibition. Sleep disorders are frequently seen in LB disease and may be an early feature. Rapid eye movement sleep behaviour disorder can be treated with clonazepam 0.25 mg at bed-time, melatonin 3 mg at bedtime, or quetiapine 12.5 mg at bedtime and titrated slowly monitoring for both efﬁ  cacy and side effects.
(7)
http://www.lewybodydementia.org/—US-based carer organization
http://lewybody.org/—UK-based carer organization
http://www.nlm.nih.gov/medlineplus/lewybodydisease.html—MEDLINE 
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Parkinson’s disease

Parkinson’s disease has been regarded as a neurological condition 
mainly affecting motor function and arising from specificlesions in the brain stem. The recognition of dementia inParkinson’s disease is of importance in management but thepossibility that motor and cognitive functions may be located in the same region of the brain is of theoretical importance.
The nature of dementia in 
There have been numerous reports of the impairment of speciﬁ  c 
cognitive functions in patients with Parkinson’s disease. Mortimer and colleagues reported cognitive impairment in 93 per cent of a substantial group of patients with Parkinson’s disease.
(1) Their data

(1) Their data 
showed neither a clear distinction between impaired groups nor the presence of subtypes of Parkinson’s disease in which cognitive impairment is a more frequent occurrence. They proposed that cognitive impairment in Parkinson’s disease lay on a continuum of severity, rather than as a feature of particular subgroups. The impairments identiﬁ  ed included deﬁ  cits in memory, language, 
visuospatial functioning, abstract reasoning, slowness in intellec-tual tasks, and difﬁ  culty in shifting from task to task. These deﬁ  cits 
are widespread among patients with Parkinson’s disease and can occur at an early stage of the disorder.
A proportion of patients with Parkinson’s disease show
impairment of a range of cognitive functions akin to the global impairment seen in Alzheimer’s disease.
(2) However, the pattern

of impairment is frequently less severe than in Alzheimer’sdisease where the pathological changes in the brain are knownto be widespread. Cognitive impairment in a range of disordersof movement where the main neuropathological changes
reside in the subcortical region of the brain led to the concept
of ‘subcortical dementia’ , a form of intellectual impairment oflesser degree than in Alzheimer’s disease, but affecting severalcognitive functions. Albert described a syndrome of which the main features were: emotional or personality changes,impaired memory, defective ability to manipulate acquiredknowledge, and a striking slowness in the rate of informationprocessing.
(3)
Many issues arose as to the nature of ‘subcortical dementia’ .

(3)
Many issues arose as to the nature of ‘subcortical dementia’ . 
Was it a clinical or a pathological concept? Was the difference between this and other forms of dementia simply one of degree? Did the pathological changes occur in the subcortical region of the brain alone? Was the syndrome of cognitive impairment distinctly different from other dementias or did the presence of motor features of the disorder simply give the intellectual impairment a distinct character? Was subcortical dementia a stable condition 
or a transitional state leading eventually to global dementia? Opinion has ranged from full acceptance of the concept to 
scepticism.
(4,5)

369
McHugh(6) suggested that the subcortical region subserves 
functions not only in motor control and cognitive function but also in the control and display of mood. He suggested that these form a ‘subcortical triad’ of symptoms most convincingly seen in Huntington’s disease. A notable difference between this concept and that of subcortical dementia was that the pathological distur-bance of mood is only intermittently present, whereas the motor and cognitive changes are persistent.
Cummings
(7) suggested that cognitive impairment in Parkinson’s

Cummings
(7) suggested that cognitive impairment in Parkinson’s 
disease takes three forms: one which is relatively mild and meets the criteria for subcortical dementia, a more severe form showing wider impairment of cognitive function but neuropathologically distinct from Alzheimer disease and a severe form which shows neuropathological changes in both the subcortical region of the brain, and in the cortex, the latter of Alzheimer type. This proposal provides a basis for viewing cognitive changes in Parkinson’s dis-ease, albeit provisional.
Many reports have suggested that global dementia occurs in 
Parkinson’s disease. Whether such a severe change in cognitive function can be regarded as an intrinsic feature of this disease, whether it implies an extension of a neuropathological process more widely in the brain, or whether it suggests a different neuro-
pathology from the outset is, as yet, uncertain. More recently the

pathology from the outset is, as yet, uncertain. More recently the 
debate has shifted to whether dementia in Parkinson’s disease, dementia with Lewy bodies and Alzheimer’s disease should be viewed as a spectrum, or as separate conditions with varying degrees of clinical and pathological overlap.
The methodology of studies of dementia in 
Research to establish the status of dementia in Parkinson’s disease 
has confronted a range of methodological issues.(8) A major problem 
is in the diagnosis of Parkinson’s disease itself. The original descrip-tion of paralysis agitans by Parkinson was the identiﬁ  cation of a 
syndrome rather than of a disease. The part played by such agents as heavy metals, infections, and vascular disease was subsequently recognized. In spite of the use of standardized methods, a substan-tial proportion of patients diagnosed as suffering from Parkinson’s disease in life do not show the expected ﬁ  ndings in the brain post-

mortem. In a follow-up study, 80 per cent of cases were shown to have neuropathological changes of Parkinson’s disease after death but over 20 per cent were diagnosed as having suffered from pro-gressive supranuclear palsy, multiple system atrophy, or Alzheimer’s disease.
(9) Furthermore, some dementing illnesses may show disor-
der of movement as a clinical feature.
Studies of dementia in Parkinson’s disease
Cases of dementia in Parkinson’s disease have been reported for over a hundred years. The frequency of dementia reported in cross-sectional or prevalence studies ranges from 0 to over 80 per cent. A recent review found a prevalence of between 28 and 44 per cent in community studies but in older samples of subjects the preva-lence was much higher.
(10)
Follow-up studies have great advantages in studying the frequency

(10)
Follow-up studies have great advantages in studying the frequency 
of dementia in Parkinson’s disease as they allow the diagnosis of Parkinson’s disease to be checked, repeated assessment reduces errors in the recognition of dementia, the pattern of evolution of dementia may be followed, the underestimation of dementia by 
selective loss through death is avoided, and they reveal the incidence rather than the prevalence of the condition. The choice of methods of diagnosis and assessment that will remain appropriate through-out the period of the follow-up remains a problem.
A prospective, controlled study in the United Kingdom reported 
an incidence of dementia of 19 per cent after 4.5 years observation. 
A later report on the same cohort of subjects showed an incidence 
of dementia of 38 per cent after 10 years of observation. The con-trol group showed cases of cognitive impairment but none amount-ing to dementia.
(11,12) A community based, prospective, controlled

(11,12) A community based, prospective, controlled 
study, in Norway, showed the risk of dementia was 5.9 times greater than in the control group.
(13) A prospective, controlled study in 
the United States showed that dementia was 3.7 times greater in the Parkinson’s disease group with severely affected, elderly patients especially at risk (Table 4.1.6.1).
(14,15)
Prediction of dementia in 
Those most likely to develop dementia are: older people, patients 
with Parkinson’s disease of longer duration, subjects who have a greater severity of motor symptoms and signs of Parkinson’s dis-ease, and those who show greater physical disability.
(11–15) Some

(11–15) Some 
studies have shown that male sex or late onset are associated with dementia. The apparent association between Parkinson’s disease treated with levodopa and dementia is probably due to improved survival.
The basic lesions are the degeneration of the pigmented neurones in the pars compacta of the substantia nigra in the brain stem; the presence of Lewy bodies  which are intracytoplasmic neuronal 
inclusions composed of abnormally phosphorylated neural ﬁ  la-
ment proteins aggregated with ubiquitin and alpha-synuclein; gliosis; and the formation of Lewy neurites  which are degenerating

ment proteins aggregated with ubiquitin and alpha-synuclein; gliosis; and the formation of Lewy neurites  which are degenerating 
neurites containing ubiquitin and alpha-synuclein. Alpha-synuclein may play an important role in the pathological process leading to the formation of Lewy bodies, but conclusive proof is lacking. Clinical Parkinson’s disease is not apparent until about 80 per cent of the nigro-striatal dopaminergic neurones have died. Lewy bodies had come to be regarded as pathognomonic of Parkinson’s disease, but are now known to be present in other diseases. An agreed though arbitrary difference between dementia in 
Parkinson’s disease and dementia with Lewy bodies is that in the 
latter, parkinsonian symptoms must not precede the occurrence of dementia by more than 12 months.
The degenerative changes in the substantia nigra are known to be

The degenerative changes in the substantia nigra are known to be 
closely linked with decreased dopaminergic neurotransmission in the brain, and this deﬁ  ciency leads to the main motor features 
of the disease, although other neurotransmitters are also deﬁ  cient. 
Some of these deﬁ  ciencies, which have been associated with cogni-
tive impairment in other disorders, include a deﬁ  ciency in acetyl-
cholinesterase in the cortex, a deﬁ  ciency of noradrenaline in the
cortex, and a deﬁ  ciency of serotonin in both striatum and cortex. 
The concentrations of a range of neuropeptides may also be altered.
The neuropathology of cases of Parkinson’s disease showing 
dementia is inconsistent; some show neuropathological changes 4.1.6 dementia in parkinson’s disease

SECTION 4  clinical syndromes of adult psychiatry 370
extending beyond the subcortical region, whereas in others neuro-
pathological changes are restricted to the subcortical region. Some studies have shown a correlation between the extent of Lewy body pathology and the severity of dementia, but others have not. Lewy bodies may be found in individuals without cognitive impairment and dementia may develop with only minimal cortical Lewy bodies.
(16) In some patients with dementia the neuropathological 
diagnosis is of Alzheimer’s disease or of other recognized degenera-tive conditions of the brain.
Just as there are difﬁ  culties in isolating Parkinson’s disease from 
other conditions, there are problems in understanding the interre-
lationships of dementing disorders. Several distinct neurodegener-ative diseases share some aetiological factors, which may represent

lationships of dementing disorders. Several distinct neurodegener-ative diseases share some aetiological factors, which may represent 
an interaction between environmental factors and the ageing process but with differing end results arising from factors speciﬁ  c 
to the process.
(17–19)  Problems in the diagnosis of Parkinson’s 
disease, the shrinking category of idiopathic Parkinson’s disease, and the difﬁ  culties occasionally encountered in explaining the 
development of dementia in the disease, suggests that the interrela-tionship between causative agents, the clinical features of disorders of movement, the occurrence of cognitive impairment, and the neuropathology of this group of disorders requires substantial further work before it is understood.
The inﬂ  uence of dementia on mortality
Dementia is associated with increased mortality. In Parkinson’s

Dementia is associated with increased mortality. In Parkinson’s 
disease increased mortality is associated with age, late age of onset of the disease, cognitive impairment, dementia, and, in some studies, male sex. Many of the studies that have been carried out have been methodologically faulty, making comparisons between 
studies and the identiﬁ  cation of the effect of particular factors, 
including dementia, problematic. One study showed a hazard ratio for Parkinson’s disease compared with controls of 1.64, in general, and of 1.94 for to Parkinson’s disease with dementia.
(20) In another 
study of mortality almost 50 per cent of those who died were demented compared with a quarter of those who survived.
(21)
Clinical aspects of Parkinson’s disease with 
dementia
The most important step in the recognition of dementia in 
Parkinson’s disease is to suspect its presence. The typical blank

(21)
dementia
Parkinson’s disease is to suspect its presence. The typical blank 
facial expression seen in Parkinson’s disease may obscure a decline 
in intellectual activity, slowness in movement may conceal intel-
lectual slowness, and sadness may suggest that morbid depression 
of mood is the reason for a reduction in liveliness. The clinical picture can usually be clariﬁ  ed by careful examination of the 
mental state. Standardized psychological tests may be useful in some cases.
The clinical importance of dementia in Parkinson’s disease is 
that there is a marked increase in disability, with problems arising in areas of functioning not previously affected by motor impair-ment alone. Dementia may be accompanied by an increased liability to confusional episodes from the toxic effects of drugs and other causes.
(22)

(22)
Management of dementia is similar to that for patients suffering 
from other dementing disorders (Chapter 4.1.3). Controlled trials suggest rivastigmine and donepezil have a moderate effect on cog-
nitive function, but tolerability can be a problem, with worsening Table 4.1.6.1 Some prospective studies of dementia in Parkinson’s disease, using control subjects and employing standardized methods of 
diagnosis and assessment
Study PD subjects (N) Control 
subjects (N)Length of 
follow-up 
(years)Diagnostic 
criteria for 
dementia  % of PD 
demented Number 
demented 
per 1000 person 
yearsDementia in PD v 
controls: relative risk 
(95% CI), †odds ratio, ‡hazard ratio
1. Biggins et al. 1992 (UK) 87 50 4.5 DSM-III-R 19 47.6  –
2. Hughes et al. 2000 (UK) 83 50 10 DSM-III-R 38 42.6  –
3. Aarsland et al. 2001 (Norway) 171 3062 4.2 DSM-III-R 33 95.3 †5.9 (3.9–9.1)
4. Levy et al. 2002 (USA) 180 180 3.6 DSM-III-R 28.9 79.9 ‡3.7 (2.1–6.3)

5. Aarsland et al. 2003 (Norway) 224 3295 8 DSM-III-R 78.2 – 2.8
6. Hobson & Meara 2004 (UK) 86 102 4 DSM-IV 35.3 107.1 5.1 (2.1–12.5)7. de Lau et al. 2005 (Holland) 139 6512 9 DSM-III-R 15.1 – ‡2.8 (1.8–4.4)
Notes on studies:
1. Prevalent cases of dementia at entry to study excluded from analysis; PD & controls assessed concurrently; DSM-III-R criteri a assessed blind; PD sample drawn from neurological clinics.
2. Same PD cohort and controls, same method of assessment as study 1.3. Community sample in Norway; controls from community sample in Demark assessed by different instruments and at different inte rvals. Prevalent cases of dementia excluded from entry 
to study. DSM-III-R criteria (dementia diagnosis) not assessed blind.

4. Community sample. Prevalent cases of dementia at entry to study excluded from analysis. Concurrent examination of PD and con trol groups using same instruments; DSM-III-R criteria 
not assessed blind.
5. Same PD cohort and controls, similar method of assessment, same method of diagnosis of dementia as study3. % PD demented inc ludes 26% cases prevalent at entry to study. Relative 
risk is for dementia in PD subjects at 4 years versus control subjects at 5 years.
6. Prevalent cases of dementia excluded from entry to study. Elderly sample. DSM-IV criteria not assessed blind.7. Community sample. Prevalent cases of dementia at entry to study excluded from analysis. DSM-III-R criteria not assessed blin d.

371
of parkinsonism and gastrointestinal upsets.(23) Rivastigmine 
is started at 1.5 mg twice daily, and increased by 3 mg per day at intervals of 4 weeks upto a maximum of 12 mg daily. Donepezil should be started at 5 mg in the evenings, increasing to 10 mg after 6 weeks, if tolerated.
http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/
CD004747/frame.html
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in Parkinson’s disease: a neuropsychological analysis. Brain and 
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 2. Pollack, M. and Hornabrook, R.W. (1966). The prevalence, natural 
history and dementia of Parkinson’s disease. Brain ,89, 429–48.
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its systems and implications for psychiatry and neurology. In Function 
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Stern), pp. 403–8. Lippincott, Williams & Wilkins, Philadelphia.
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diagnosis of idiopathic Parkinson’s disease: a clinico–pathlolgical study of 100 cases. Journal of Neurology, Neurosurgery, and Psychiatry ,55,
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longitudinal study of dementia in Parkinson’s disease. Journal of 
Neurology, Neurosurgery, and Psychiatry ,55, 566–71.
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in Parkinson’s disease: a community based, prospective study. Neurology ,56, 730–6.
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4.1.7 Dementia due to 
Huntington’s disease
Huntington’s disease (HD) was ﬁ  rst described in 1872 by an

Huntington’s disease (HD) was ﬁ  rst described in 1872 by an 
American physician living on Long Island, New Y ork. His father and grandfather practised medicine in the same community, so he had access to case notes from several generations of families who lived there. This long period of record keeping allowed him to document a hereditary form of chorea, similar to ‘common (Sydenham’s) chorea’ , but progressing over many years to death. Its sufferers had a tendency to insanity and suicide. Huntington’s brief essay, which also included a clear description of autosomal dominant inheritance, remains one of the classical descriptions of a medical disorder.
(1)
Clinical features and course of illness

(1)
Huntington’s disease is an inherited neuropsychiatric disorder mainly affecting the striatum and its direct connections. It is char-acterized by a triad of clinical features that are common to diseases of this region: a non-aphasic dementia ,depression  and other disor-
ders of mood, and a variety of dyskinesias , most typically chorea.
(2,3)
Chorea, from the Greek word for ‘dance’ , describes involuntary

(2,3)
Chorea, from the Greek word for ‘dance’ , describes involuntary 
non-stereotyped jerky movements. The illness, insidious in onset, may begin with all or any one of these three features. Patients who present initially to psychiatrists usually have dementia, loss of temper, or depression, often with suicidal thoughts or attempts. Symptoms may appear at any time from early childhood to old age, most frequently between 35 and 45 years of age. Once the illness begins, sufferers gradually deteriorate over many years in their cognitive and motor functioning and end in a persistent vegetative state with almost complete loss of voluntary motor 4.1.7 dementia due to huntington’s disease

SECTION 4  clinical syndromes of adult psychiatry 372
function. Death occurs after about 16 years and is usually caused 
by inanition or aspiration pneumonia. Some patients die earlier from suicide or subdural haematoma caused by a fall. Patients with early onset progress more rapidly than those whose symptoms begin later in life.
Pathology and genetics
The earliest visible neuropathology is in the striosomes of the caudate/putamen,
(4) followed by a dorsal-to-ventral progressive 
loss of almost all striatal output neurones. The deep layers of mult iple

cortical regions are also prominently affected, and there can also be milder neuronal loss in some brainstem nuclei. Protein aggre-gates, most easily detectable in neuronal nuclei, are prominent. Neuroimaging studies have shown that neuropathological changes typically begin before the onset of clinically detectable disease. In particular, the extent of striatal loss in presymptomatic individuals, as measured by MRI, correlates with the predicted time until dis-ease onset.
(5) Cortical thinning(6) and white matter loss and disor-
ganization(7,8) have also been detected in presymptomatic gene 
carriers. Subtle changes that may be related to abnormal brain development have also been reported.
The disorder, with a point prevalence of about 6/100 000,
(9) is

(9) is 
caused by the expansion of an unstable triplet repeat sequence (CAG) in the ﬁ  rst exon of a gene near the telomere of chromosome 
4p.
(10) It is transmitted as an autosomal dominant trait; if one

4p.
(10) It is transmitted as an autosomal dominant trait; if one 
parent is affected, each offspring (regardless of sex) has an indepen-dent 50 per cent chance of inheriting the abnormal gene. Normal repeat lengths range from about 7 to 28 triplets. Individuals with29–35 triplets will not develop HD but may pass an expanded allele to an offspring, while individuals with 40 or more triplets will develop HD. Repeat lengths of 36–39 triplets may or may not cause disease. The rate of mutation from a normal-length allele to an expanded one is low, so that most patients have an affected parent. Family history, however, can be obscured by multiple factors, including misdiagnosis of the parent, death of the parent before disease onset, adoption, and incorrect paternity. The repeat length does not remain stable at meio-sis. In HD, the number of CAG triplets is more likely to increase when the gene is transmitted by fathers. As the number of repeats increases,

the age at onset is earlier. Thus, paternal transmission is often associ-
ated with ‘anticipation’ , earlier onset in the subsequent generation; most individuals with childhood onset have affected fathers.
(11)
The pathogenesis of HD is not well understood but appears to be 
multifaceted. The gene, huntingtin , with the expanded repeat is 
expressed as a protein, huntingtin. The CAG repeat expansion is translated as an expanded polyglutamine tract, which appears to have neurotoxic properties. The region of the huntingtin protein with the polyglutamine tract may be cleaved from the rest of the pro-tein and adopt an abnormal conﬁ  guration. This in turn is thought to

lead to disruption of cellular functions, including transcriptional machinery, protein degradation processes, and cellular transport. It is also possible that the expansion mutation results in a partial loss of the normal functions of huntingtin, one of which is the stimula-tion of the neurotrophic factor BDNF; decreased BDNF may con-tribute to neurotoxicity.
(12)
Diagnosis
The most difﬁ  cult aspect of diagnosis is to think of HD in the 
differential. Diagnosis remains dependent on a thorough psychiatric history, including a detailed family history and history of changes 
in social adjustment, mental state examination, including a cogni-tive examination, and neurological examination. The features vary, depending on how long the patient has been ill.
(13) Once the dis-
ease is suspected, genetic testing, available through many commer-cial laboratories, provides the deﬁ  nitive diagnosis.
Diagnosis of patients with early symptoms

Patients with HD who initially consult psychiatrists present with a 
variety of psychiatric syndromes, including depression, bipolar dis-order, obsessive–compulsive disorder, schizophrenia, or excessive anxiety. Irritability is common with any of these or may appear outside the context of another syndrome. These psychiatric syn-dromes are clinically indistinguishable from idiopathic disorders and may be the only manifestation of HD for several years. It is during this prodromal phase that patients often commit suicide; this may occur even if the patient is unaware of his risk for HD.
(14)

(14)
Presenting symptoms and problems with functioning at work or at home must often be elicited from an informant; the patient may minimize them, be embarrassed, or even unaware of them. These include declines in work speed or accuracy, which may have result-ed in demotion or warnings from superiors; a tendency to become irritated or physically aggressive in response to annoying stimuli that would not have elicited such a response in the past; and a decreased interest in activities. Most of these symptoms and behav-iours are common in psychiatric disorders, but the cognitive inef-ﬁ ciency and irritability may seem to be out of proportion, relative 
to the patient’s other symptoms. On cognitive examination, the patient may have difﬁ  culty recalling dates of important life events 
and more difﬁ  culty than expected with ‘serial sevens’ . Usually, the 
cognitive changes are easier to notice after the psychiatric disorder

cognitive changes are easier to notice after the psychiatric disorder 
is treated, which can usually be accomplished using standard medications. However, unlike idiopathic disorders, cognitive inef-ﬁ ciency and difﬁ  culties at work, apathy (if present), and sometimes 
irritability remain even after the patient’s mood, energy, and sleep patterns have improved. When this happens in the course of treat-ment of depression, a dementia work-up should be considered and the family history further scrutinized through hospital records and other family informants.
On neurological examination, motor restlessness is usually present 
but is easily misinterpreted as a manifestation of anxiety. Motor signs may be subtle: slightly slow saccadic eye movements,
(15)
writhing movements of the protruded tongue or of the ﬁ  ngertips 
when the arms are held at 90 °, or mild disdiadochokinesis.

(15)
Diagnosis can be further complicated by the apparent lack of a 
family history of HD. The family may not have been informed about the affected parent’s diagnosis, or may know only that a parent died in a psychiatric institution or committed suicide. In other cases the paternity is uncertain. If the family history is actually negative (this is quite uncommon) or unobtainable (often the case for adopted individuals who frequently present in childhood), the diagnosis may be conﬁ  rmed by testing for the HD gene expansion.
(a) Diagnosis in childhood and adolescence
When HD starts in childhood or early adolescence,(16) motor signs

When HD starts in childhood or early adolescence,(16) motor signs 
include parkinsonian-like motor slowness of voluntary movement, with lead pipe or cogwheel rigidity and very slow saccades. Occasional children have a coarse tremor; later myoclonus isseen. Cognitively, the rate of learning in school slows, handwriting

373
deteriorates, and interest in school and social activities declines.(17)
Of the patients who present with a schizophrenic syndrome, most 
are adolescents. Psychosis and loss of cognitive capacity may be the only clinical features for several years before motor impairment begins. Children with HD often have seizures, which are usually grand mal. Sometimes myoclonus is mistaken for seizures.
(b) The importance of early diagnosis
Even though it can be difﬁ  cult, it is important to make the diagno-
sis of HD as early as possible, particularly in employed persons. Poor function at work (or in schoolwork or household duties) occurs early, and patients can lose their jobs, often on suspicion of drug or alcohol abuse. This is usually avoided if the diagnosis is made known to the family and employer, allowing modiﬁ  cation of

the work environment or retirement on the basis of disability. Prompt diagnosis does not mean that the patient needs to be informed of the diagnosis at that same time. Some patients are too depressed to do this safely; others indicate that they do not wish to be told. Treatment can usually proceed despite the patient’s reluctance to label the disorder.
Diagnosis of patients with well-established 
signs and symptoms
After a few years of illness, diagnosis is easier. The signs and symp-
toms will have worsened, and usually the motor disorder is obvi-ous. A typical patient who has been ill for about 5 to 7 years is unable to work or manage ﬁ  nances, but lives at home and is able to

toms will have worsened, and usually the motor disorder is obvi-ous. A typical patient who has been ill for about 5 to 7 years is unable to work or manage ﬁ  nances, but lives at home and is able to 
manage personal needs. Some patients remain active and energetic, continuing to participate as fully in life as their cognitive and motor disabilities allow; others are apathetic most of the time, but irrita-ble when disturbed; still others have severe depression with delu-sions, obsessions, or compulsions, and most are anxious and easily upset by changes of routine. An uncommon, but very troublesome, feature of HD is sexual abnormality. While most patients become impotent or uninterested in sex, a few are hypersexual and may develop paraphilias.
(18) It is important to inquire about these 
specifically because neither the patient nor spouse will likely mention it.
Cognitively, patients complain of forgetfulness and becoming

Cognitively, patients complain of forgetfulness and becoming 
easily distracted. Thinking is slow; patients have difficultyfollowing a conversation and cannot complete a multistaged task. On cognitive examination, Mini Mental State Examination scores
(19) may still be above the 23 cut-off score, but serial sevens 
will be very poor, and one or two items will be missed on recalling words after a distraction. On neuropsychological testing, IQwill be lower than expected for education, and there will bedifﬁ culty learning word lists and performing tests that require 
changing sets.
Most patients will have obvious involuntary choreic movements, 
as well as difﬁ  culty with control of voluntary motor movements,

as well as difﬁ  culty with control of voluntary motor movements, 
as seen by clumsiness, slowness, dysarthria, and an unsteady gait. The involuntary movements will wax and wane with the level of arousal; it can be worsened by performing serial 7 s or by ﬁ  ne motor 
tasks. Speech will have an irregular staccato, often laboured, quality. Saccadic eye movements will be slow or irregular, and the patient will be obviously clumsy on diadochokinesis and ﬁ  nger-thumb 
tapping, although ﬁ  nger-to-nose testing is normal. Gait will be 
wide based and irregular, with difﬁ  culty with tandem walking. 
Reﬂ exes are usually brisk, and a history of falls can be elicited.Diagnosis of patients with advanced disease
After 10 years of illness, dementia is more severe, with poor perfor-
mance on all aspects of the cognitive examination except naming. Speech is dysﬂ  uent with long lapses between the examiner’s ques-

tion and the patient’s reply, rather like Brocca’s aphasia. Some patients will be almost unable to speak, although language compre-hension is relatively preserved. Patients (if they are cooperative) can carry out simple commands and will recognize relatives and nursing staff. Patients may be irritable, particularly when their ver-bal requests cannot be understood or when routines are altered. Psychiatric syndromes are more difﬁ  cult to discern, but most can 
be diagnosed by observing behaviour such as hoarding, sleepless-ness, or diurnal variation in mood. Physical disabilities are much 
worse. Patients often need to be fed, toileted, and helped with most daily needs. They have difﬁ  culty walking and may fall, causing fur-
ther disability through broken limbs or subdural haematomas. Chorea often stabilizes or subsides,
(13) but the ability to carry out

(13) but the ability to carry out 
voluntary movements becomes seriously handicapping. If they survive long enough, patients become unable to initiate speech, swallow with great difﬁ  culty, are unable to walk, and have such 
severely rigid muscle tone that they may be nearly unable to move their bodies. Clonus and positive Babinski signs are present. Patients in this sort of ‘persistent vegetative state’
(20) are difﬁ  cult to 
distinguish from individuals with other advanced movement dis-orders or dementias; as in early disease, diagnosis will depend on eliciting a family history or genetic testing.
The differential diagnosis of HD is extensive,(3) but only a few of 
the disorders for which it can be mistaken are common.(2) These

the disorders for which it can be mistaken are common.(2) These 
include other dementias, other movement disorders, and other psychiatric disorders. The most frequent subcortical dementia is Parkinson’s disease , which has a similar motor slowness, but a pill-
rolling tremor and festinating gait are rare in HD. The dementia associated with late-life depression  can look very similar to HD, 
including motor slowness. Alzheimer’s disease  is easily distin-
guished by the lack of motor signs during the ﬁ  rst several years of 
illness and more prominent difﬁ  culty with memory and language, 
as opposed to attention and calculation. Perhaps most difﬁ  cult to 
distinguish clinically are the frontotemporal dementias , which 
present with prominent behavioural disturbances and a positive family history. The clinical presentation may be insufﬁ  cient to dis-

tinguish these various dementias in patients with advanced disease, since they all progress to a persistent vegetative state. The family 
history and the duration of illness (which is longer for HD than for 
Alzheimer’s disease or frontotemporal dementia) can be helpful.
Several other diseases classiﬁ  ed as movement disorders  include 
all the features of the subcortical triad. They often have an autoso-mal dominant inheritance pattern and expansion of unstable trimeric repeat sequences. These include Fahr’s syndrome (calciﬁ  -

cation of the striatum), some forms of spinocerebellar degenera-tion, chorea acanthocytosis, Huntington’s disease-like 2 (HDL2), and dentatorubropallidolusian atrophy (DRPLA). The latter three disorders, while much rarer than HD, can look so similar that they can only be distinguished by genetic testing and by a blood smear for acanthocytes. The most common movement disorder that resembles HD is tardive dyskinesia . Patients with HD occasionally 
have several years of hallucinations and delusions before the4.1.7 dementia due to huntington’s disease

SECTION 4  clinical syndromes of adult psychiatry 374
movement disorder begins. If they have been treated with neuro-
leptics, the subsequent onset of involuntary movements can be mistaken for tardive dyskinesia. On the other hand, the choreoath-etotic involuntary movements of severe tardive dyskinesia may involve the trunk and extremities as well as the face and can be mistaken for HD. Usually, it is possible to distinguish the patients with tardive dyskinesia by their normal saccadic eye movements, normal tandem gait, and ﬂ  uid and ﬂ  uent speech.
(21) However,

(21) However, 
genetic testing may be necessary in some cases. Wilson’s disease also presents with the subcortical triad and should be considered when neither of the parent is affected. It is recessively inherited, so that the only affected relatives are siblings. Very late-onset HD may be diagnosed as ‘senile chorea’ because the family history appears to be negative. Family members will also present symptoms only late in life and may have died before their manifestation.
The differential diagnosis of nearly all psychiatric disorders
includes HD, as described above.
Treatment and management
Currently, no treatment inﬂ  uences the course of illness of HD, but 
based on research on likely genetic mechanisms, clinical trials of agents protective against oxidants, excitotoxicity, and metabolic stress are underway. No agent yet tested has had a dramatic beneﬁ  t.

The development of biochemical assays and cell and animal models that mimic various aspects of HD can be used to screen for effec-tive therapies.
It is possible to alleviate some of the symptoms of HD. Small 
doses of neuroleptics can be helpful in decreasing involuntary movements in the ﬁ  rst stages of the illness, as can tetrabenazine 
and occasionally benzodiazepines. Doses of more than 5 mg. of haloperidol do not further decrease chorea and may worsen cogni-tion and cause motor stiffness and slowing.
(22) Persons with the 
advanced form of the disease are often unresponsive to neuroleptics. 
Treatment of psychiatric manifestations signiﬁ  cantly improves

Treatment of psychiatric manifestations signiﬁ  cantly improves 
quality of life for the patients and their families. Clinical experience suggests that depression, anxiety, and obsessive–compulsive disor-der associated with HD usually respond to the pharmacological treatments used for the similar idiopathic disorders. SSRIs can be particularly helpful. Because some patients seem unaware of their depressed mood (just as they can be unaware of their involuntary movements) an informant is often needed to elicit the symptoms. It is also important to distinguish depression (from which the patient is miserable and sleepless) and apathy, which does not cause distress. Occasionally, mood and anxiety disorders are chronic and unresponsive to treatment. Severe, unresponsive depression can be 
treated successfully with electroconvulsive therapy.
(23) Bipolar dis-

order in patients with HD does not usually respond to lithium, but may improve with carbamazepine or valproic acid. Valproic acid, serotonin speciﬁ  c reuptake inhibitors, and low dose antipsychotic 
agents may also be helpful in the treatment of irritability. Lithium is difﬁ cult to administer because patients require high ﬂ  uid intake and 
easily become lithium toxic if ﬂ  uid intake is insufﬁ  cient. In one case 
report, high doses of sertraline were effective for intractable aggres-sion.
(24) Schizophrenic symptoms can be difﬁ  cult to treat. Sometimes 
a combination of an antipsychotic, including clozaril, with an anti-
depressant will prove helpful. Muscle rigidity and consequent
contractions occur in late HD, causing pain and difﬁ  culty in posi-
tioning the patient to avoid pressure sores. Amantadine (which also has a positive effect on mood) can somewhat decrease the rigidity;

tioning the patient to avoid pressure sores. Amantadine (which also has a positive effect on mood) can somewhat decrease the rigidity; 
chairs and beds must be padded and tailored to each patient’s speciﬁ  c needs.
Family and environment
As with most dementias, psychopathology inﬂ  uences, and is inﬂ  u-
enced by, the patient’s environment. Patients do best in a calm, highly predictable environment where cognitive expectations are not too complicated. When the environment is too taxing, patients become irritable, especially towards their family. HD seriously damages family relationships, which in turn affects the patient. The well spouse becomes responsible for supporting the family, caring for children and the patient, and making family and ﬁ  nancial deci-
sions. Spouses’ lives are further complicated by patients’ unwilling-ness to relinquish ﬁ  nancial and family decision-making; patients

sions. Spouses’ lives are further complicated by patients’ unwilling-ness to relinquish ﬁ  nancial and family decision-making; patients 
usually make poor decisions that damage family relationships and ﬁ nances. Some patients neglect their children or treat them badly. 
If the other parent cannot prevent this, it is wisest to remove the patient from the home. There is no research on the treatment of sexual aggression, which occasionally occurs in males, but the author has successfully treated a few males with depot progester-one. Supportive psychotherapy for the patient should focus on minimizing demoralization at lost abilities. Spouses can be helped to reorganize family life in ways that maximize the predictability of the patient’s environment, diplomatically decrease patients’ domes-tic responsibilities. It is crucial that the spouse has time away from the patient.
Helping persons at risk for HD

People at risk for HD vary in their abilities to deal with the burden of uncertainty, depending on their personal attributes and their experience with the illness in a relative. A few consult physicians for reassurance, but most avoid doctors unless they become ill, and even then many resist medical attention, claiming against all evi-dence that they are perfectly well. Currently, a minority of asymp-tomatic persons at risk for HD decide to have genetic testing, but these individuals, skewed towards those whose anxiety is lessened by planning for the future, have usually handled the test results well, regardless of its outcome.
(25) When clinical trials are launched

(25) When clinical trials are launched 
for individuals with the HD mutation who are without detectable symptoms, the incentive for presymptomatic testing will likely increase, with a concomitant change in the nature of individuals seeking testing. Foetal and pre-implantation genetic testing are now available in some centers, each with its own set of potentially complicated ethical and practical issues to be sorted out prior to testing.
Presymptomatic genetic testing of any sort should always be 
preceded by genetic counselling, provided either by a genetic coun-selor or by a clinician familiar with HD genetics and the potential 
practical and psychological consequences of both positive and neg-ative test results. Counselling should include a discussion of the motivations for seeking testing, which may include decisions about childbearing, education, employment, ﬁ  nances, participation in 
clinical trials, or the potential at-risk status of offspring. Many

clinical trials, or the potential at-risk status of offspring. Many 
individuals who come for testing have not seriously considered the possibility that they will test positive for the mutation, so that role playing about various outcome scenarios is important. Occasionally, persons request testing who have learned only recently that they are

375
at risk for HD. Others apply who are depressed or under unusual 
stress for other reasons. Such persons should be encouraged to delay testing until their situation becomes more settled. Finally, some people who request testing already have symptoms of HD, yet do not wish to have a diagnosis. Considerable care is required to decide how best to support such individuals, and family members or close friends of the person should be consulted.
(26)
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4.1.8 Vascular dementia
Vascular dementia is the second most frequent cause of dementia.(1,2)
Because vascular causes of cognitive impairment are common, 
may be preventable, and the patients could beneﬁ  t from therapy, 
early detection, and accurate diagnosis of vascular dementia is desirable.
(3)
Vascular dementia is not only multi-infarct dementia, but is 
related to other vascular mechanisms and pathological changes in the brain, and has other causes and clinical manifestations. Vascular dementia is not a disease, but a syndrome. The origin of this syn-drome reﬂ  ects complex interactions between vascular aetiologies

(cerebrovascular disorders and vascular risk factors), changes in the brain (infarcts, white-matter lesions, atrophy), host factors (age, education), and cognition.
(4–8)
Conceptual issues related to of vascular dementia include the 
deﬁ nition of the cognitive syndrome (type, extent, and combina-
tion of impairments in different cognitive domains), and the vascular causes (vascular aetiologies and changes in the brain). Variations in these deﬁ  nitions has led to different estimates of point 
prevalence, to different groups of patients, and to reports of differ-ent types and distribution of brain lesions.
(9–11)  The cognitive 
syndrome of vascular dementia is characterized by predominate executive dysfunction rather than deﬁ  cits in memory and language 
function.
(12) Although the course of cognitive decline may be 4.1.8 vascular dementia

SECTION 4  clinical syndromes of adult psychiatry 376
stepwise, it is often slowly progressive, and may include periods of 
stability or even some improvement.
The relationship between vascular lesions in the brain and cog-
nitive impairment is important, but which type, extent, side, site, and tempo of vascular lesions in the brain relates to different types of vascular dementia is not established in detail.
(4–6,13)
Current criteria for vascular dementia are based on the concept 
of cerebral infarcts. For example the widely used NINDS-AIREN criteria include dementia, cerebrovascular disease, and a relation-ship between these two disorders. The main tools for the diagnosis include detailed history, neurological examination, mental state examination, relevant laboratory examinations, and preferably magnetic resonance imaging of the brain.
Vascular dementia research, until recently overshadowed by that

Vascular dementia research, until recently overshadowed by that 
into Alzheimer’s disease, is now developing rapidly. There is great promise for intervention. Developments in classiﬁ  cation, diagnosis, 
and treatment are likely.
Aetiology and pathophysiology
Aetiology
The main causes of vascular dementia are cerebrovascular disorders and their risk factors. The prevalent cerebrovascular disorders include large artery disease (artery-to-artery embolism, occlusion of an extra- or intracranial artery), cardiac embolic events, small-vessel disease (lacunar infarcts, ischaemic white-matter lesions) and haemodynamic mechanisms.
(13–15) Less frequent causes include 
speciﬁ  c arteriopathies including cerebral autosomal dominant

speciﬁ  c arteriopathies including cerebral autosomal dominant 
arteriopathy with subcortical infarcts and leucoencephalopathy (CADACIL) and cerebral amyloid angiopathy (CAA), haemor-rhage (intracranial haemorrhage, subarachnoidal haemorrhage), haematological factors, venous disease, and hereditary disorders. There may be as yet undiscovered causes.
In most patients diagnosed with vascular dementia, several 
aetiological factors are involved. However, the roles these factors play have not been identiﬁ  ed in detail, and it is not certain which 
of these mechanisms distinguish vascular dementia from cerebro-vascular disease without dementia.
(4,5,7,16,17)
Risk factors for vascular dementia can be divided into vascular 
factors (e.g. arterial hypertension, atrial ﬁ  brillation, myocardial

factors (e.g. arterial hypertension, atrial ﬁ  brillation, myocardial 
infarction, coronary heart disease, diabetes, generalized atheroscle-rosis, lipid abnormalities, smoking), demographic factors (e.g. age, education), genetic factors (e.g. family history, individual genetic features), and stroke-related factors (e.g. type of cerebrovascular disease, site and size of stroke).
(18,19) Hypoxic ischaemic events 
(cardiac arrhythmias, congestive heart failure, myocardial infarc-tion, seizures, pneumonia) may be an important risk factor for incident dementia in patients with stroke.
(20)
Changes in the brain
Vascular dementia is related to both ischaemic and non-ischaemic changes in the brain.
(4,5,13,14)  The ischaemic lesions include arterial 
territorial infarct, distal ﬁ  eld (watershed) infarct, lacunar infarct,

territorial infarct, distal ﬁ  eld (watershed) infarct, lacunar infarct, 
ischaemic white-matter lesions, and incomplete ischaemic injury. Incomplete ischaemic injury incorporates laminar necrosis, focal gliosis, granular atrophy, and incomplete white-matter infarction.
(21,22) In addition, both focal (around the ischaemic 
lesion) and remote (disconnection, diaschisis) functional ischaemic changes relate to vascular dementia, and the volume of functionally inactive tissue exceeds that of focal ischaemic lesions in vascular 
dementia.
(23) Limitation in current clinical methods have 
hampered the detection of both incomplete ischaemic injury and functional ischaemic changes related to vascular dementia. Atrophy is the non-ischaemic factor related to vascular dementia. However, there are no methods to distinguish between ischaemic and degen-erative causes of atrophy clinically.
Brain imaging ﬁ  ndings

Work on the relationship between brain lesions and cognition in 
vascular dementia has used varying deﬁ  nitions and measures of 
cognitive impairment, varying techniques to reveal brain changes, and varying criteria for the selection of patients.
(17)
CT and magnetic resonance imaging ( MRI ) studies on vascular 
dementia have shown that bilateral ischaemic lesions are impor-tant.
(4,5,7,17) Some studies emphasize deep infarcts in the frontal 
and limbic areas, while others report cortical lesions especially in the temporal and parietal areas. There is disagreement about the number and volume of the infarcts, as well as the extent and location of atrophy. Diffuse and extensive white-matter lesions have been suggested as an important factor leading to functional disconnection of cortical brain areas. Some general conclusions on brain lesions in vascular dementia may be drawn.
1 There is no single pathological feature, but a combination of

1 There is no single pathological feature, but a combination of 
infarcts, ischaemic white-matter lesions of varying size and type, and atrophy of varying degree and site.
2 Infarcts associated with vascular dementia tend to be bilateral, 
multiple (more than two), and located in the dominant hemi-sphere and in the limbic structures (frontolimbic or prefrontal–subcortical and medial–limbic or medial–hip pocampal cir cuits).
3 White-matter lesions on CT or magnetic resonance imaging 
(MRI) associated with vascular dementia are extensive, extend-ing in periventricular white matter, and conﬂ  uent to extending 
in the deep white matter.
4 It is doubtful whether a single small lesion on imaging can be 
accepted as evidence for vascular dementia.
5 Absence of cerebrovascular lesions on CT or MRI is contrary to a 
diagnosis of vascular dementia.
Pathophysiology

The extent to which pathological changes in the brain cause, com-pound, or only coexist with the vascular dementia syndrome is still uncertain. The vascular changes in the brain can be the main cause of cognitive impairment (as assumed in vascular dementia
(24,25) ), 
they can contribute to the clinical picture of other dementia syn-dromes including Alzheimer’s disease (AD),
(7,26) or they may be 
coincidental. The occurrence of infarcts may cause an earlier pre-sentation of clinical symptoms in a brain in which there is existing and progressive Alzheimer’s disease pathology.
(26)
It is not certain which are the critical changes in the brain leading

(26)
It is not certain which are the critical changes in the brain leading 
to the clinical picture of vascular dementia. The syndrome has been related to the volume of brain infarcts (with a critical threshold), the number of infarcts, the site of infarcts (bilateral, in strategic cortical or subcortical, or affecting white matter), to other isch-aemic factors (incomplete ischaemic injury, delayed neuronal death, functional changes), to the atrophic changes (origin, location, extent), and ﬁ  nally to the additive effects of other pathologies

377
(Alzheimer’s disease, Lewy body dementia, frontal lobe dementias). 
But it is uncertain which type, extent, side, site, and tempo of vascular lesions in the brain, and which combination with other pathologies, relate to vascular dementia.
(4–6,13)
Classiﬁ  cation and clinical criteria
Vascular dementia has been divided into subtypes on the basis of 
clinical, radiological, and neuropathological features. It is uncer-tain whether these subtypes are distinct disorders, with separate pathological and clinical features, and responses to therapy.
(27)
If homogenous subtypes could be identiﬁ  ed the comparability 
of research studies would be greater and multicentre studies easier.
(28)
The subtypes of vascular dementia included in most classiﬁ  cations 
include multi-infarct dementia (cortical lesions), small-vessel demen-tia or subcortical ischaemic vascular disease and dementia (SIVD) (subcortical deep lesions), and strategic infarct dementia.
(12,14,27,29–33)

Many include also hypoperfusion dementia.(12,14,30,34) Further sug-
gested subtypes include haemorrhagic dementia, hereditary vascular dementia, and combined or mixed dementia (Alzheimer’s disease with cerebrovascular disease).
DSM-IV
(35) does not specify subtypes. ICD-10(36) includes 
six subtypes (acute onset, multi-infarct, subcortical, mixed cortical and subcortical, other, and unspeciﬁ  ed). The NINDS-AIREN crite-
ria
(30) include, without detailed description, cortical vascular 
dementia, subcortical vascular dementia, Binswanger’s disease, 
and thalamic dementia. In addition separate research criteria for 
subcortical vascular dementia, the SIVD, have been proposed.(37)
Main subtypes
Multi-infarct dementia or cortical vascular dementia, and small-vessel dementia or subcortical vascular dementia are the two com-
mon subtypes, although their frequencies vary in different series.
(12,14,31)
Cortical vascular dementia  relates to large-vessel disease, cardi-

ac embolic events, and hypoperfusion. Infarcts are predominantly in the cortical and corticosubcortical arterial territories, and their distal ﬁ  elds (watershed). Typical clinical features are lateralized 
sensorimotor changes and the abrupt onset of cognitive impair-ment and aphasia.
(31) A combination of different cortical neuro-
psychological syndromes has been suggested to occur in cortical vascular dementia.
(38)
Subcortical vascular dementia , small-vessel dementia, the 
SIVD(33,37) incorporates the entities ‘lacunar state’ and ‘Binswanger’s 
disease’ . It relates to small-vessel disease and hypoperfusion, with predominately lacunar infarcts, focal and diffuse ischaemic white-matter lesions, and incomplete ischaemic injury.
(31,33,37–39)

Clinically, small-vessel dementia is characterized by pure motor hemiparesis, bulbar signs, dysarthria, depression, and emotional lability, and especially deﬁ  cits in executive functioning.
(38–41)
Clinical criteria
Since the 1970s several clinical criteria for vascular dementia have 
been published.(11,42,43) The most widely used include those in 
DSM-IV ,(35) ICD-10,(36) and NINDS-AIREN.(30)
The two cardinal elements of any clinical criteria for vascular 
dementia are the deﬁ  nition of the cognitive syndrome(44) and the deﬁ nition of the cause.(11,43,45) All clinical criteria are consensus 
criteria, derived neither from prospective community-based studies on vascular factors affecting the cognition, nor on detailed natural histories.

(28,30,42,43,46) All these criteria are based on the 
concept of ischaemic infarcts. They are designed to have high spec-iﬁ city, but have been poorly validated.
(42,46) An important conse-
quence of the different deﬁ  nitions of the dementia syndrome,(9,44)
and the vascular cause,(10,11) is that the different diagnostic criteria 
identify different populations.
The DSM-IV deﬁ  nition of vascular dementia (Table 4.1.8.1) 
requires focal neurological signs and symptoms or laboratory evi-dence of focal neurological damage clinically judged to be related to the disturbance.
(35) The course is speciﬁ  ed by sudden cognitive 
and functional losses. The DSM-IV criteria do not detail brain imaging requirements. The DSM-IV deﬁ  nition of vascular demen-
tia is reasonably broad and lacks detailed clinical and radiological guidelines.

The ICD-10 criteria
(36) (Table 4.1.8.2) require unequal distribu-
tion of cognitive deﬁ  cits, focal signs as evidence of focal brain dam-
age, and signiﬁ  cant cerebrovascular disease judged to be aetiologi-
cally related to the dementia. The criteria do not detail brain imaging requirements. The ICD-10 criteria specify six subtypes of vascular dementia (Table 4.1.8.3). The ICD-10 criteria for vascular dementia have been shown to be highly selective and only some of those fulﬁ  lling the general criteria for ICD-10 vascular dementia Table 4.1.8.1  The DSM-IV deﬁ  nition of vascular dementia
Focal neurological signs and symptoms (e.g. exaggeration of deep tendon 
 reﬂ  exes, extensor plantar response, pseudobulbar palsy, gait abnormalities, 
 weakness of an extremity, etc.)
or
Laboratory evidence of focal neurological damage (e.g. multiple infarctions 
 involving cortex and underlying white matter)

weakness of an extremity, etc.)
or
The cognitive deﬁ  cits cause signiﬁ  cant impairment in social or occupational 
 functioning and represent a signiﬁ  cant decline from a previously higher 
 level of functioning
The focal neurological signs, symptoms, and laboratory evidence are judged 
 to be aetiologically related to the disturbance
The deﬁ  cits do not occur exclusively during the course of deliriumCourse characterized by sustained periods of clinical stability punctuated by 
 sudden signiﬁ  cant cognitive and functional losses
Table 4.1.8.2  The ICD-10 criteria for vascular dementia
Unequal distribution of deﬁ  cits in higher cognitive functions with some 
 affected and others relatively spared. Thus, memory may be quite markedly 
 affected while thinking, reasoning, and information processing may show 
 only mild decline

affected and others relatively spared. Thus, memory may be quite markedly 
There is evidence for focal brain damage, manifest as at least one of the 
 following: unilateral spastic weakness of the limbs, unilaterally increased 
 tendon reﬂ  exes, an extensor plantar response, pseudobulbar palsy
There is evidence from the history, examination, or test of signiﬁ  cant 
 cerebrovascular disease, which may reasonably be judged to be 
 aetiologically related to the dementia (history of stroke, evidence of 
 cerebral infarction)4.1.8 vascular dementia

SECTION 4  clinical syndromes of adult psychiatry 378
can be classiﬁ  ed into one of the subtypes.(11,45) The shortcoming of 
these criteria include lack of detailed guidelines (e.g. of unequal cognitive deﬁ  cits and changes on neuroimaging), lack of aetio-
logical criteria, and heterogeneity.
(11,45)
The NINDS-AIREN research criteria for vascular dementia(30)
include a dementia syndrome, cerebrovascular disease, and a rela-tionship between these (Table 4.1.8.4). Cerebrovascular disease is deﬁ ned by the presence of focal neurological lesions and brain 
imaging evidence of ischaemic changes in the brain. A relationship between dementia and cerebrovascular disorder is inferred from the onset of dementia within 3 months following a recognized stroke, or on abrupt deterioration in cognitive functions, or ﬂ  uctu-
ating stepwise progression of cognitive deﬁ  cits. The criteria include

ating stepwise progression of cognitive deﬁ  cits. The criteria include 
a list of features consistent with the diagnosis, as well as a list of features that make the diagnosis uncertain or unlikely. Also, differ-ent levels of certainty of the clinical diagnosis (probable, possible, deﬁ nite) are included. The NINDS-AIREN criteria recognize het-
erogeneity
(47) of the syndrome and variability of the clinical course 
in vascular dementia, and highlight detection of ischaemic lesions and a relationship between lesion and cognition, as well as stroke and dementia onset.
The NINDS-AIREN criteria are currently most widely used in 
clinical drug trials on vascular dementia. In a neuropathological series, sensitivity of the NINDS-AIREN criteria was 58 per cent and speciﬁ  city 80 per cent.
(48) The criteria successfully excluded 
Alzheimer’s disease in 91 per cent of cases, and the proportion of combined cases misclassiﬁ  ed as probable vascular dementia was 
29 per cent.

(48) The inter-rater reliability of the NINDS-AIREN 
criteria is moderate to substantial ( κ = 0.46–0.72).(49)
These three sets of criteria for vascular dementia are not inter-
changeable; they identify different numbers and clusters of patients. The DSM-IV criteria are less restrictive than the ICD-10 and NINDS-AIREN criteria.
(11,50)Vascular cognitive impairment
Vascular cognitive impairment (VCI) is currently considered the most recent modiﬁ  cation of the terminology to reﬂ  ect the all-
encompassing effects of vascular disease or lesions on cognition and incorporates the complex interactions between vascular aetiologies, risk factors, and cellular changes within the brain and cognition.
(51,52)
VCI refers to all aetiologies of CVD including vascular risks

(51,52)
VCI refers to all aetiologies of CVD including vascular risks 
which can result in brain damage leading to cognitive impairment. The impairment encompasses all levels of cognitive decline, from the earliest deﬁ  cits to a severe and broad dementia-like cognitive 
syndrome.
(51,53)  VCI cases that do not meet the criteria for dementia 
can also be labelled as VCI with no dementia, vascular CIND.(54)
VCI may include cases with cognitive impairment related to 
hypertension, diabetes, or atherosclerosis, transient ischaemic 
attacks, multiple corticosubcortical infarcts, silent infarct, strategic Table 4.1.8.3  Characteristics of the vascular dementia subtypes 
in ICD-10
Acute onset (F01.0)
The dementia develops rapidly (i.e. usually within 1 month but within no 
  longer than 3 months) after a succession of strokes, or (rarely) after a single 
large infarction
Multi-infarct (F01.1)
The onset of the dementia is more gradual (i.e. within 3-6 months) following

longer than 3 months) after a succession of strokes, or (rarely) after a single 
The onset of the dementia is more gradual (i.e. within 3-6 months) following 
  a number of minor ischaemic episodes. Comments: it is presumed that 
there is an accumulation of infarcts in the cerebral parenchyma. Between 
the ischaemic episodes there may be periods of actual clinical improvement
Subcortical (F01.2)
A history of hypertension, and evidence from clinical examination and special 
  investigations of vascular disease located in the deep white matter of the 
cerebral hemispheres, with preservation of the cerebral cortex.
Mixed cortical and subcortical (F01.3)
Mixed cortical and subcortical components of vascular dementia may be 
 suspected from the clinical features, the results of investigation, or both
Other (F01.8)
Unspeciﬁ  ed (F01.9)
In the ICD-10 criteria no speciﬁ  c diagnostic guidelines are given for these

suspected from the clinical features, the results of investigation, or both
In the ICD-10 criteria no speciﬁ  c diagnostic guidelines are given for these 
 two vascular dementia sybtypesTable 4.1.8.4  The NINDS-AIREN criteria for probable vascular 
dementia
(I)  The criteria for the clinical diagnosis of PROBABLE vascular dementia 
 include all of the following
1 Dementia
2   Cerebrovascular disease,  deﬁ  ned by the presence of focal signs on 
  neurological examination, such as hemiparesis, lower facial weakness, 
Babinski sign, sensory deﬁ  cit, hemianopia, dysarthria, etc. consistent with 
stroke (with or without history of stroke), and evidence of relevant CVD by brain imaging (CT or MRI) including multiple large-vessel strokes 
or a single strategically placed infarct (angular gyrus, thalamus, basal

or a single strategically placed infarct (angular gyrus, thalamus, basal 
forebrain, PCA or ACA territories), as well as multiple basal ganglia and white-matter lacunes or extensive periventricular white-matter lesions, 
or combinations thereof
3  A relationship between the above two disorders,  manifested or 
  inferred by the presence of one or more of the following
  (a)  Onset of dementia within 3 months following a recognized stroke  (b)  Abrupt deterioration in cognitive functions, or ﬂ  uctuating stepwise 
progression of cognitive deﬁ  cits
(II)  Clinical features consistent with the diagnosis of PROBABLE vascular 
 dementia include the following
    (a)  Early presence of a gait disturbance (small-step gait or marche a 
petits-pas,  apraxic–ataxic or parkinsonian gait)
    (b) History of unsteadiness and frequent unprovoked falls    (c)  Early urinary frequency, urgency, and other urinary symptoms not 
explained by urological disease

(b) History of unsteadiness and frequent unprovoked falls    (c)  Early urinary frequency, urgency, and other urinary symptoms not 
    (d)  Personality and mood changes, abulia, depression, emotional 
incontinence, other subcortical deﬁ  cits including psychomotor retardation and abnormal executive function
(III)  Features that make the diagnosis of vascular dementia uncertain or 
 unlikely include the following
    (a)  Early onset of memory deﬁ  cit and progressive worsening of memory 
and other cognitive functions such as language (transcortical sensory aphasia), motor skills (apraxia), and perception (agnosia), in the 
absence of corresponding focal lesions on brain imaging
    (b)  Absence of focal neurological signs, other than cognitive 
disturbance
    (c) Absence of cerebrovascular lesions on brain CT or MRI
CVD, cerebrovascular disease; PCA, posterior cerebral artery; ACA, anterior cerebral artery.

379
infarcts, small-vessel disease with white-matter lesions an lacunae, 
as well as AS pathology with coexisting CVD.(55) The concept and 
deﬁ nitions of VCI and vascular CIND are still evolving, but it seems 
clear that the diagnosis should not be conﬁ  ned to a single aetiology 
comparable to the traditional ‘pure AD’ concept.(51,52)
Cognitive syndrome
The cognitive syndrome of vascular dementia is characterized by memory deﬁ  cit, dysexecutive syndrome, slowed information pro-
cessing, and mood and personality changes. These features are found especially among patients with subcortical lesions. Patients with cortical lesions often have additional cortical neuropsycho-logical syndromes.
(38)
The memory deﬁ  cit in vascular dementia is often less severe 
than in Alzheimer’s disease. It is characterized by impaired recall, rela-tively intact recognition, and more beneﬁ  t from cues.
(56) The dysex-

ecutive syndrome in vascular dementia includes impairment in goal formulation, initiation, planning, organizing, sequencing, executing, set-sifting and set-maintenance, as well as in abstracting.
(12,38,56)  The 
dysexecutive syndrome in vascular dementia relates to lesions affect-ing the prefrontal subcortical circuit including prefrontal cortex, caudate, pallidum, thalamus, and the thalamocortical circuit (capsu-lar genu, anterior capsule, anterior centrum semiovale, and anterior 
corona radiata).
(57) Typically, personality and insight are relatively 
preserved in mild and moderate cases of vascular dementia.
Features that make the diagnosis of vascular dementia disease 
uncertain or unlikely include early and progressive worsening 
of episodic memory, and other cognitive cortical deﬁ  cits in the

of episodic memory, and other cognitive cortical deﬁ  cits in the 
absence of corresponding focal lesions on brain imaging.(30)
Neurological ﬁ  ndings
Frequent neurological ﬁ  ndings indicating focal brain lesion early 
in the course of vascular dementia include mild motor or sensory deﬁ cits, decreased co-ordination, brisk tendon reﬂ  exes, Babinski’s 
sign, visual ﬁ  eld loss, bulbar signs including dysarthria and dyspha-
gia, extrapyramidal signs (mainly rigidity and akinesia), disordered gait (hemiplegic, apraxic–ataxic, or small-stepped), unsteadiness, unprovoked falls, and urinary frequency and urgency.
(30,31,39–41)
Features that make the diagnosis of vascular dementia uncertain or unlikely include absence of focal neurological signs, other than cognitive disturbance.
(30)
In cortical vascular dementia, typical clinical features are lateral-

(30)
ized sensorimotor changes and abrupt onset of cognitive impair-ment and aphasia, and in subcortical vascular dementia disease pure motor hemiparesis, bulbar signs, dysarthria, disordered gait and unsteadiness.
(31)
Behavioural and psychological symptoms of dementia
Depression, anxiety, emotional lability and incontinence, and other psychiatric symptoms are frequent in vascular dementia. Depression, abulia, emotional incontinence, and psychomotor retardation are especially frequent in subcortical vascular dementia disease.
(12,38)
(a) Ischaemic scores
Cardinal features of vascular dementia disease are incorporated in the Hachinski Ischaemia Score
(58) (Table 4.1.8.5). In a neuropa thological series, stepwise deterioration (odds ratio, 6.0), ﬂ  uctuating course

(58) (Table 4.1.8.5). In a neuropa thological series, stepwise deterioration (odds ratio, 6.0), ﬂ  uctuating course 
(odds ratio, 7.6), history of hypertension (odds ratio, 4.3), history of stroke (odds ratio, 4.3), and focal neurological symptoms (odds ratio, 4.4) differentiated patients with deﬁ  nite vascular dementia 
from those with deﬁ  nite Alzheimer’s disease.
(59) Nocturnal confu-
sion and depression did not discriminate. However, the ischaemia score was unable to differentiate the Alzheimer’s disease patients with cerebrovascular disease from those with vascular dementia.
Traditionally, vascular dementia has been characterized by a relative abrupt onset (days to weeks), a stepwise deterioration (some recovery after worsening), and ﬂ  uctuating course (e.g. differences

between days) of cognitive functions. These features are seen in patients with repeated lesions affecting cortical and corticosub-cortical brain structures, i.e. large-vessel multi-infarct vascular dementia, and with watershed infarcts related to haemodynamic problems. However, in patients with small-vessel dementia, i.e. subcortical vascular dementia, the onset is more insidious and course more slowly progressive.
(28,30,39,60)
The mean duration of vascular dementia is around 5 years.(2)
In most studies survival is less than for the general population or those with Alzheimer’s disease.
(61,62)  Surprisingly little is known 
about the rate and pattern of cognitive decline, either overall or among different subgroups of vascular dementia.
(63) This under-
lines the lack of studies detailing the natural history of vascular dementia.

The clinical evaluation of patients with memory impairment has two stages, the symptomatic diagnosis, i.e. evaluation of the type and extent of cognitive impairment, and the aetiological diagnosis, i.e. evaluation of vascular cause(s) and related factors. The symp-tomatic categories other than dementia include the more mild cognitive stages, i.e. VCI or vascular CIND, delirium, circumscribed Table 4.1.8.5  Hachinski ischaemia score
Item Score value
Abrupt onset 2
Stepwise deterioration 1Fluctuating course 2Nocturnal confusion 1Relative preservation of personality 1Depression 1Somatic complaints 1Emotional incontinence 1History of hypertension 1History of strokes 2Evidence of associated atherosclerosis 1Focal neurological symptoms 2Focal neurological signs 24.1.8 vascular dementia

SECTION 4  clinical syndromes of adult psychiatry 380
neuropsychological syndromes (e.g. aphasia) and functional 
psychiatric disorders (e.g. depression).(46) Stages of aetiological 
diagnosis include diagnosis of the speciﬁ  c causes, especially the 
potentially treatable conditions, evaluation of secondary factors able to affect the cognitive functioning, and more detailed differen-tiation between speciﬁ  c causes, especially that between vascular 
dementia disease and Alzheimer’s disease.
Clinical evaluation
The cornerstone in the evaluation of a patient with suspected vascular dementia is detailed clinical and neurological history and examination, including interview of a close informant. Assessment of social functions, activities of daily living, as well as psychiatric and behavioural symptoms, is part of the basic evaluation. These patients are challenging and enough time should be allocated time for the consultation, often 40 to 60 min.
Mental status examination

Bedside mental status examination includes the Mini-Mental State Examination.
(64) However, this has limitations as it emphasizes 
language, does not include timed elements and the recognition portion of the memory tests, is insensitive to mild deﬁ  cits, and is 
inﬂ uenced by education and age. Other proposed screening instru-
ments for vascular dementia include a 10-word memory test with delayed recall, cube drawing test for copy, verbal ﬂ  uency test (num-
ber of animals named in 1 min), Luria’s alternating hand sequence, or ﬁ nger rings and letter cancellation test (neglect).
(30) Other test 
include the Clox and Exit designed to screen the dysexecutive features.
(65)
Frequently a more detailed neuropsychological test is needed.

(65)
Frequently a more detailed neuropsychological test is needed. 
It should cover the main cognitive domains including memory functions (working memory, episodic memory, semantic memory), abstract thinking, judgement, aphasia, apraxia, agnosia, orienta-tion, attention, executive functions, and speed of information processing.
(44,66)
Brain imaging
Brain imaging should be performed at least once during the initial diagnostic workout. MRI is preferred because it has high sensitivity and the ability to demonstrate medial temporal lobe and basal forebrain areas. Depending on the criteria of vascular dementia used, focal brain infarcts have been revealed in 70 to 100 per cent, and more extensive white-matter lesions in 70 to 100 per cent of cases.
(13,25,30,67,68)
Single-photon emission CT and positron-emission tomography 
may reveal patchy reduction of regional blood ﬂ  ow and metabo-

lism, as well as decreased white-matter ﬂ  ow and metabolism.(69)
Other investigations
Chest X-ray, electrocardiography, and screening laboratory tests 
are part of the basic evaluation.(15,70,71)  In selected cases extended 
laboratory investigations, analysis of the cerebrospinal ﬂ  uid, and 
EEG are performed, as well as examinations of the extra- and intra-cranial arteries and detailed cardiological investigations.
(15,70,71)
In vascular dementia EEG is more often normal than in 
Alzheimer’s disease, and if abnormal more frequently suggests a focal abnormality. Abnormalities increase with more severe intel-lectual decline both in vascular dementia disease and Alzheimer’s disease.
(60)At present there is no specific laboratory test for vascular

(60)At present there is no specific laboratory test for vascular 
dementia. T ests may reveal risk factors and concomitant disorders such as hyperlipidaemia, diabetes, and cardiac abnormality.
(60)
Apolipoprotein E4 is a established risk factor for Alzheimer’s 
disease, but its relationship to vascular dementia has not been 
consistent.(72) Determination of apolipoprotein E status is currently 
not part of clinical evaluation in vascular dementia.
Differential diagnosis of vascular dementia disease
(a) Alzheimer’s disease
Typical Alzheimer’s disease is characterized by insidious onset and slowly progressive intellectual deterioration, absence of symptoms and signs indicating focal brain damage, and absence of any other speciﬁ  c disease affecting the brain.
(73) Alzheimer’s disease 
has typical clinical stages ranging from early changes to profound dementia.
(74,75)
When patients with vascular dementia have a clinical history,

(74,75)
When patients with vascular dementia have a clinical history, 
neurological examination, and brain imaging ﬁ  ndings compatible 
with ischaemic changes of the brain, the differentiation from Alzheimer’s disease can be made clinically.
(25)
Diagnostic problems arise when Alzheimer’s disease is combined 
with cerebrovascular disease. Difﬁ  cult clinical problems include 
stroke unmasking Alzheimer’s disease in patients with post-stroke dementia, insidious onset, and/or slow progressive course in vascu-lar dementia patients, and cases where it is difﬁ  cult to assess the

role of white-matter lesions or of infarcts found on neuroimaging. A solution to recognize patients with Alzheimer’s disease and cerebrovascular disease would be to discover reliable biological markers for clinical AD. Other potential markers include early prominent episodic memory impairment, early and signiﬁ  cant 
medial temporal lobe atrophy on magnetic resonance imaging, bilateral parietal hypoperfusion on single-photon emission com-puted tomography and low concentrations of cerebrospinal ﬂ  uid 
amyloid peptides with high tau protein concentrations. The dis-
tinction would be also less difﬁ  cult if there were more detailed 
knowledge of the sites, type, and extent of ischaemic brain changes critical for vascular dementia, and the extent and type of medial temporal lobe atrophy critical for Alzheimer’s disease.
Other important conditions to be differentiated from vascular 
dementia include normal pressure hydrocephalus,
(76) frontal lobe

(76) frontal lobe 
tumours and other intracranial masses,(15) Lewy body disease,(77)
frontotemporal degenerations,(78) Parkinson’s disease and 
dementia,(79) progressive supranuclear palsy,(80) and multisystem 
atrophy.(81)
Vascular dementia is the second most common cause of dementia accounting for 10 to 50 per cent of cases, depending on thegeographic location, patient population, and clinical methods used.
(1,2) The prevalence of vascular dementia is from 1.2 to 4.2 per 
cent of persons aged 65 years and older, and the incidence is6 to 12 cases per 1000 persons aged over 70 years per year.
(2)
The prevalence and the incidence of vascular dementia disease increases with increasing age, and men seem to have a higherprevalence of vascular dementia than women. Epidemiology of vascular dementia has been affected by variations in the deﬁ  nition

of the disorder, the clinical criteria used, and the clinical methods applied.
(18,82,83)

381
The frequency of vascular dementia disease has been higher than 
previously reported in recent series comprising older subjects.(10)
Stroke and cerebrovascular disorders relate also to a high risk of cognitive impairment and dementia.
(24,84)  Finally, vascular factors 
such as stroke and white-matter lesions have a clinical effect on 
Alzheimer’s disease.(26) Thus, vascular factors may even be the
leading cause of cognitive impairment worldwide especially when cognitive impairment as opposed to dementia is considered.
(51,85)
Treatment
The objectives of targeted treatment of vascular dementia include symptomatic improvement of core symptoms (e.g. cognitive, behavioural), slowing progression of the disorder, and treatment of secondary factors affecting cognition (e.g. depression, anxiety, agitation).
A number of drugs have been studied in the symptomatic treat-

ment of vascular dementia including cerebro- and vasoactive drugs, nootropics, and some calcium antagonists, but largely these studies have shown negative results.
(86) Studies on symptomatic improve-
ment in vascular dementia have mostly had small numbers, short treatment periods, variations in diagnostic criteria and tools, mixed populations, and have had variation in clinical endpoints applied.
First nimodipine,
(87) memantine,(88) and propentofylline(89)
raised expectations for a symptomatic treatment of vascular dementia. However, all the studies failed to fulﬁ  l the current 
requirement by the regulators for and treatment indication in vascular dementia.
(90,91)
More recently cholinesterase inhibitors (donepezil, galantamine,

(90,91)
More recently cholinesterase inhibitors (donepezil, galantamine, 
rivastigmine) have been tested in large randomized controlled trials in patients with probable vascular dementia. All showed sig-niﬁ cant cognitive improvement compared to placebo, but failed to 
show signiﬁ  cantly better global outcome with the Alzheimer-type 
measures. Accordingly, none of the acetylcholinesterase inhibitors have received marketing authorization for the treatment of vascu-lar dementia.
(91) Patients with Alzheimer’s disease with coexisting 
cerebrovascular disease show good beneﬁ  t from galantamine.(92)
Possibilities for prevention
For primary prevention the target is the brain at risk of cerebrovas-

cular disease and cognitive impairment. The methods relate to the treatment of putative risk factors of vascular dementia, and the promotion of potential protective factors. Risk factors include those related to cerebrovascular disorders and stroke, to vascular dementia, to post-stroke dementia, to white-matter lesions, and to cognitive impairment or dementia, and also those related to Alzheimer’s disease.
(8) The vascular risk factors include arterial 
hypertension, atrial ﬁ  brillation, myocardial infarction, coronary 
heart disease, diabetes, generalized atherosclerosis, lipid abnormal-ities, and smoking. The demographic factors include age and education. One putative protective factor is oestrogen.
(93)
Knowledge of effects of primary prevention on these risk factors

(93)
Knowledge of effects of primary prevention on these risk factors 
in populations free of cognitive impairment is still scant.(8,94)  In a 
European study, treatment of mild systolic hypertension decreased the incidence of dementia.
(95) Positive effects in primary preven-
tion of stroke support the idea that action on vascular risk factors could reduce the numbers of patients with vascular dementia.For secondary prevention the target is the brain already affected 
by cerebrovascular disease and at risk of vascular dementia. Actions

by cerebrovascular disease and at risk of vascular dementia. Actions 
include diagnosis and treatment of acute stroke in order to limit the extent of ischaemic brain changes, prevention of recurrence of stroke, and treatment of risk factors. Treatment is guided by the aetiology of cerebrovascular disorder such as large artery disease (e.g. aspirin, dipyridamole, carotid endarterectomy), cardiac embolic events (e.g. anticoagulation, aspirin), small-vessel disease (e.g. antiplatelet therapy), and haemodynamic mechanisms(e.g. control of hypotension and cardiac arrhythmias).
(15,29,46) A 
recent large study showed some beneﬁ  t from perindopril and inda-
pamide in the prevention of post-stroke dementia.(96) Hypoxic 
ischaemic events (cardiac arrhythmias, congestive heart failure, myocardial infarction, seizures, pneumonia) are an importantrisk factor for incident dementia in patients with stroke and should be taken into account in the secondary prevention of vascular dementia.
(20)

(20)
Detailed knowledge of the effects of secondary prevention of 
vascular dementia is lacking. In a small series of patients with established vascular dementia, control of high arterial blood pres-sure,
(97) cessation of smoking,(97) and use of aspirin(98) improved 
or stabilized cognition. It has been suggested that lowering of plasma viscosity could also have an effect in vascular dementia.
(99)
The absence of progressive cognitive decline in patients receiving placebo in treatment trials of vascular dementia may also reﬂ  ect 
an effect of intensiﬁ  ed risk factor control.
(89)
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163, 1069–75.4.1.8 vascular dementia

SECTION 4  clinical syndromes of adult psychiatry 384
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4.1.9 Dementia due to HIV disease
Mario Maj
The ﬁ  rst description of a syndrome consisting of cognitive, motor, 
and behavioural disturbances in patients with AIDS was published 
in 1986.(1) The syndrome was named ‘AIDS dementia complex’ . 
In 1990, the World Health Organization (WHO) introduced the term ‘HIV-associated dementia’ ,
(2) pointing out that subclinical or

(2) pointing out that subclinical or 
mild cognitive and/or motor dysfunctions without impairment of performance in daily living activities cannot be subsumed under the term ‘dementia’ . The expression ‘mild cognitive/motor disorder’ was proposed for those conditions. The same distinction was made in 1991 by the American Academy of Neurology,
(3) which identi-
ﬁ ed an ‘HIV-associated dementia complex’ and an ‘HIV-associated 
minor cognitive/motor disorder’ . The present chapter focuses on the dementia syndrome associated with HIV infection.

The onset of HIV-associated dementia is usually insidious. Early cog-nitive symptoms include forgetfulness, loss of concentration, mental slowing, and reduced performance on sequential mental activities of some complexity (the subject misses appointments, or needs lists to recall ordinary duties; loses track of conversations or his or her own train of thought; needs additional time and effort to organize thoughts and to complete daily tasks). Early behavioural symptoms include apathy, reduced spontaneity and emotional responsivity, and social withdrawal (the subject becomes indifferent to his or her per-sonal and professional responsibilities; his or her work production decreases, as well as the frequency of social interactions; the subject complains of early fatiguability, malaise, and loss of sexual drive). Depression, irritability or emotional lability, agitation, and psychotic symptoms may also occur. Early motor symptoms include loss of

balance and coordination, clumsiness, and leg weakness; the subject 
is less precise in normal hand activities, such as writing and eating, drops things more often than usual, trips and falls more frequently, and perceives the need to exercise more care in walking.
(1,4)
Routine mental status tests, in this early stage, may be normal or 
show only slowing in verbal or motor responses and/or difﬁ  culty in 
recalling a series of objects after 5 min or more. Neurological exam-ination may show tremor (best seen when the patient sustains a posture, such as holding the arms and ﬁ  ngers outstretched), hyper-
reﬂ exia (particularly of the lower extremities), ataxia (usually seen 
only on rapid turns or tandem gait), slowing of rapid alternating movements (of the ﬁ  ngers, wrists, or feet), frontal release signs 
(snout reﬂ  ex, palmar grasp), dysarthria. T ests of ocular motility may show interruption of smooth pursuits, and slowing or inac-
curacy of saccades.

In the late stages of the disease, there is usually a global deteriora-
tion of cognitive functions and a severe psychomotor retardation. Speech is slow and monotonous, with word-ﬁ  nding difﬁ  culties 
and possible progression to mutism. Patients become unable to walk, due to paraparesis, and usually lie in bed indifferent to their illness and their surroundings. Bladder and bowel incontinence are common. Myoclonus and seizures may occur. Pedal paraesthesias and hypersensitivity may appear, due to concurrent sensory neuropathy. The level of consciousness is usually preserved, except for occasional hypersomnolence.
The WHO criteria for HIV-associated dementia(2) are as follows:
1 The research criteria for dementia of the ICD-10 are met, with 
some modiﬁ  cations:

(a)  dec line in memory may not be severe enough to impair 
activities of daily living;
(b)  decline in motor function ma y be present, and is veriﬁ  ed 
by clinical examination and, when possible, formal neuro-psychological testing;
(c) the minimum requested duration of symptoms is 1 month;
(d) aphasia, agnosia, and apraxia are unusual.
2 Laboratory evidence for systemic HIV infection is present.3 No evidence of another aetiology from history, physical 
examination, or laboratory tests should be present (speciﬁ  cally, 
cerebrospinal ﬂ  uid analysis and either computed tomography 
(CT) or magnetic resonance imaging (MRI) should be done to exclude active central nervous system opportunistic processes).
The American Academy of Neurology criteria
(3) require the 
following:

1 Laboratory evidence for systemic HIV infection.2 Acquired abnormality in at least two of the following cognitive 
abilities (present for at least 1 month): attention/concentration, speed of processing of information, abstraction/reasoning, visuospatial skills, memory/learning, and speech/language.
3 At least one of the following:
(a) acquired abnormality in motor function or performance;
(b) decline in motivation or emotional control or change in 
social behaviour.
4 Absence of clouding of consciousness during a period long 
enough to establish the presence of 2.
5 Absence of evidence of another aetiology.
Both the WHO and the American Academy of Neurology criteria

Both the WHO and the American Academy of Neurology criteria 
distinguish three levels of severity of the dementia syndrome (mild, moderate, and severe), on the basis of the degree of the impairment in activities of daily living.
Neuropsychological tests
Neuropsychological examination supports the clinical diagnosis of HIV-associated dementia, by providing evidence of cognitive and

385
motor dysfunction. Moreover, it may be useful in the differential 
diagnosis with a depressive syndrome.
The most prominent impairment is observed on tests of ﬁ  ne 
motor control (ﬁ  nger tapping, grooved pegboard), rapid sequential 
problem solving (trail-making A and B, digit symbol), visuospatial problem solving (block design), spontaneity (verbal ﬂ  uency), and 
visual memory (visual reproduction). In contrast, naming and vocabulary skills are largely preserved even in the most advanced 
cases.
The signs that should alert to the possible presence of a depres-
sive ‘pseudodementia’ are as follows:
(5)
1 the intratest variability of performance (i.e. missing easy items 
and then correctly answering more difﬁ  cult questions);
2 mood-congruent complaints, which are at odds with objective 
performance (i.e. the subject complains of having difﬁ  culties 
with a test, whereas his or her performance is near perfect);
3 responses of ‘I don’t know’ or giving up, which are followed by

3 responses of ‘I don’t know’ or giving up, which are followed by 
the correct answer, when the subject is further urged to respond.
It should be considered, however, that dementia and depression 
may coexist in HIV-seropositive subjects.
Brain imaging provides additional support to the diagnosis of HIV-associated dementia, especially by excluding central nervous system opportunistic processes, in particular cerebral toxoplasmo-sis and primary central nervous system lymphoma.
The predominant ﬁ  nding in HIV-associated dementia is cerebral 
atrophy: both CT and MRI demonstrate widened cortical sulci and, less commonly, enlarged ventricles. Furthermore, MRI frequently shows high-intensity signal abnormalities on the T
2-weighted

2-weighted 
image (diffuse widespread involvement, patchy localized involve-ment, focal distinct areas of involvement, or punctuate white-matter hyperdensities). These lesions are without mass effect and are most commonly located in the periventricular white matter and the centrum semiovale (less frequently, in the basal ganglia or in the thalamus).
As to differential diagnosis, both CT and MRI are able to demon-
strate the multiple bilateral ring-enhancing lesions that are charac-teristic of cerebral toxoplasmosis, and the contrast-enhancing mass lesions of primary central nervous system lymphoma.
Cerebrospinal ﬂ  uid analysis
Cerebrospinal ﬂ  uid analysis can support the clinical diagnosis of

Cerebrospinal ﬂ  uid analysis can support the clinical diagnosis of 
HIV-associated dementia, especially by excluding several central nervous system opportunistic infections, in particular cryptococcal meningitis.
The most frequent cerebrospinal ﬂ  uid ﬁ  ndings in HIV-associated 
dementia are the increase of total proteins and of the IgG fraction 
and index. A mononuclear pleocytosis may occur. The presence of 
the HIV core antigen p24 can be detected, although this ﬁ  nding 
is possible also in neurologically normal subjects. HIV RNA can be demonstrated in the cerebrospinal ﬂ  uid by using the polymerase 
chain reaction. Increased cerebrospinal ﬂ  uid levels of neopterin, 
β
2-microglobulin, and quinolinic acid (non-speciﬁ  c markers of 
immune activation), soluble Fas and Fas ligand (associated with apoptosis), as well as several cytokines (interleukin 1 β, interleukin 6, 
tumour necrosis factor- α), have been reported, but may be detected

tumour necrosis factor- α), have been reported, but may be detected 
also during central nervous system opportunistic infections.As to differential diagnosis, Indian ink staining, cryptococcal 
antigen titres, and fungal culture can be decisive for the identiﬁ  ca-
tion of cryptococcal meningitis. Other central nervous system opportunistic infections that can be identiﬁ  ed by cerebrospinal 
ﬂ uid analysis include central nervous system tuberculosis, cyto-
megalovirus encephalitis, and neurosyphilis.
There has been a decrease in the incidence of HIV-associated dementia after the introduction of highly active antiretroviraltherapy (HAART): while between 1990 and 1992 the meanincidence was 21.1 cases per 1000 person-years, between 1996 and 1998 it decreased to 10.5 cases per 1000 person-years.
(6) However, 
the incidence seems to have increased again in 2003.(7) A post-

mortem neuropathologic study reported that, while severe HIV encephalopathy was not detected anymore in the HAART era, the prevalence of mild and moderate encephalopathy increased,probably reflecting the longer survival time after initial HIVinfection.
(8)
Pathogenesis
HIV crosses the blood-brain barrier by a Trojan-horse-type mech-anism, using the macrophages it infects.
(9) Once in the brain, 
it infects glial cells. Infected and activated macrophages and microglia release neurotoxins which lead to neuronal damage and apoptosis.
(10) It is possible that direct effects of viral proteins on 
neurones also contribute to neurodegeneration. Post-mortem studies have revealed the presence of HIV in frontal lobes, subcor-tical white matter and the basal ganglia.
(11)

(11)
In the pre-HAART era, HIV-associated dementia often progressed rapidly to severe deterioration and death, especially in patients with advanced systemic disease. T oday, many patients present an attenuated form which is slowly progressive or static. The mean survival, which was 5 months in 1993–1995, increased to 38.5 mo nths
in 1996–2000.
(12) Prominent psychomotor slowing, a history of 
intravenous drug use and low CD4 T-lymphocyte count seem to predict a more rapid progression.
(13)
Available treatments
Antiretrovirals are not always successful in crossing the blood-brain barrier, but, as mentioned above, have been able to reduce the incidence and modify the course of HIV-associated dementia. There is evidence that they can improve speciﬁ  c aspects of cogni-

tive functioning, such as psychomotor speed performance, in people with HIV-associated dementia.
(14) The optimal HAART 
regimen for the treatment of HIV-associated dementia has not been established.
Neuroprotective drugs whose beneficial effect on cognitive 
performance in patients with HIV infection has been preliminarily documented include the monoamine oxidase inhibitor deprenyl(a putative antioxidant and antiapoptotic agent) and peptideT (which blocks the HIV gp120 envelope protein). Other investiga-tional drugs include memantine and nitroglycerin (which areN-methyl- d-aspartate receptor antagonists), nimodipine (a calcium-
channel blocker), pentoxifylline (an inhibitor of the production 4.1.9 dementia due to hiv disease

SECTION 4  clinical syndromes of adult psychiatry 386
and activity of tumour necrosis factor- α), and lexipafant (an antag-
onist of platelet-activating factor).
The psychostimulant methylphenidate has been found to be use-
ful in treating apathy and cognitive slowing in patients with HIV-associated dementia, with relatively mild side effects. Only anec-dotal evidence is available concerning the usefulness of cholinesterase inhibitors such as donepezil.
Patients with AIDS, when treated with typical antipsychotic 
drugs for the presence of psychotic symptoms or behavioural dys-control, are particularly prone to develop extrapyramidal side effects and neuroleptic malignant syndrome. According to prelimi-nary research evidence, some atypical antipsychotics are well toler-ated even by patients who had to stop standard neuroleptics due to extrapyramidal side effects.
AIDS patients with depressed mood have been found to respond

AIDS patients with depressed mood have been found to respond 
to tricyclic antidepressants and selective serotonin reuptake inhibi-tors (SSRIs) as well as HIV-seronegative subjects. There is a pre-liminary evidence that SSRIs (or at least some of them) are better tolerated than tricyclic antidepressants, except in patients with 
diarrhoea.
Patients with HIV-associated dementia often have additional dis-
ease processes which may aggravate the cognitive impairment, including secondary infections and metabolic disturbances. These conditions should be adequately diagnosed and managed.
An appropriate HAART regimen should be implemented

An appropriate HAART regimen should be implemented 
and constantly monitored (taking into account that cognitive dys-function may have a negative impact on adherence to treatment). If psychotic symptoms, behavioural dyscontrol, or mood distur-bances are present, the same strategies which are used for other people with these problems should be implemented, taking into account that HIV-infected patients have an increased sensitivity to the side effects of antipsychotics and antidepressants, and that adverse interactions may occur between psychotropic drugs and antiretrovirals (for instance, the administration of St. John’s Wort 
induces the metabolism of the protease inhibitor indinavir, thus 
decreasing its serum concentration to levels which may cause treat-ment failure).
(15) Methylphenidate (5–20 mg/day) may be used to 
reduce apathy and psychomotor slowing.
Psychosocial interventions in HIV-associated dementia should

Psychosocial interventions in HIV-associated dementia should 
include maintenance of a structured daily schedule, titration of external stimuli, restriction to familiar environments, frequent orienting interactions with signiﬁ  cant others, and monitoring of 
personal and ﬁ  nancial affairs. Psychoeducational intervention with 
families and signiﬁ  cant others is also essential.
The care of patients with HIV-associated dementia will make 
increasing demands on health services, as well as on volunteer and 
community support systems. It is uncertain, at present, whether 
such care is best provided in specialized units (e.g. inpatient AIDS 
units), or within general psychiatric or medical services. Special 
management problems may arise when the behavioural distur-bance (e.g. poor impulse control, sexual acting-out behaviour) is such as to constitute a risk for other patients or staff members.

management problems may arise when the behavioural distur-bance (e.g. poor impulse control, sexual acting-out behaviour) is such as to constitute a risk for other patients or staff members. 
Placement of patients in the terminal stage of the disease may also 
represent a problem: the lack of appropriate options in the com-munity may obstruct their timely and humane discharge from the hospital.Further information
Dougherty, R.H., Skolasky, R.L., and McArthur, J.C. (2002). Progression 
of HIV-associated dementia treated with HAART. The AIDS Reader ,
12, 69–74.
Kaul, M. and Lipton, S.A. (2006). Mechanisms of neuronal injury and death 
in HIV-1 associated dementia. Current HIV Research ,4, 307–18.
Maj, M., Starace, F., and Sartorius, N. (1993). Mental disorders in HIV-1 
infection and AIDS . Hogrefe and Huber, Bern.
 1. Navia, B.A., Jordan, B.D., and Price, R.W. (1986). The AIDS dementia 
complex: I. clinical picture. Annals of Neurology ,19, 517–24.

 2. World Health Organization. (1990). Report of the Second Consultation 
on the Neuropsychiatric Aspects of HIV-1 Infection, Geneva, 11–13 January 1990. World Health Organization, Geneva.
 3. American Academy of Neurology AIDS Task Force. (1991). 
Nomenclature and research case deﬁ  nitions for the neurological 
manifestations of human immunodeﬁ  ciency virus type-1 infection. 
Neurology ,41, 778–85.
 4. Maj, M. (1990). Organic mental disorders in HIV-1 infection. AIDS ,
4, 831–40.
 5. Van Gorp, W.G., Satz, P ., Hinkin, C., et al. (1989). The 
neuropsychological aspects of HIV-1 spectrum disease. Psychiatric 
Medicine ,7, 59–78.
 6. Sacktor, N., Lyles, R.H., Skolasky, R., et al. (2001). HIV-associated

 6. Sacktor, N., Lyles, R.H., Skolasky, R., et al. (2001). HIV-associated 
neurologic disease incidence changes: multicenter AIDS cohort study, 1990–1998. Neurology ,56, 257–60.
 7. McArthur, J.C. (2004). HIV dementia: an evolving disease. Journal of 
Neuroimmunology ,157, 3–10.
 8. Neuenburg, J.K., Brodt, H.R., Herndier, B.G., et al. (2002). HIV-
related neuropathology, 1985 to 1999: rising prevalence of HIV encephalopathy in the era of highly active antiretroviral therapy. Journal of Acquired Immune Deﬁ  ciency Syndromes ,31, 171–7.
 9. Lawrence, D.M. and Major, E.O. (2002). HIV-1 and the brain: 
connections between HIV-1-associated dementia, neuropathology and neuroimmunology. Microbes and Infection ,4, 301–8.
10. Nath, A. (2002). Human immunodeﬁ  ciency virus (HIV) proteins in 
neuropathogenesis of HIV dementia. Journal of Infectious Diseases ,
186(Suppl. 2), S193–8.

11. Kaul, M., Garden, G.A., and Lipton, S.A. (2001). Pathways to neuronal 
injury and apoptosis in HIV-associated dementia. Nature ,410, 988–94.
12. Dore, G.J., McDonald, A., Li, Y., et al. (2003). Marked improvement in 
survival following AIDS dementia complex in the era of highly active 
antiretroviral therapy. AIDS ,17, 1539–45.
13. Bouwman, F.H., Skolasky, R., Hes, D., et al. (1998). Variable progression 
of HIV-associated dementia. Neurology ,50, 1814–20.
14. Sacktor, N.C., Lyles, R.H., Skolasky, R., et al. (1999). Combination 
antiretroviral therapy improves psychomotor speed performance in 
HIV-seropositive homosexual men. Neurology ,52, 1640–6.
15.     Piscitelli, S.C., Burstein, A.H., Chaitt, D., et al. (2000). Indinavir 
concentrations and St. John’s Wort. Lancet ,355, 547–8.

387
4.1.10 The neuropsychiatry 
of head injury
Head injury ‘imparts at a blow both physical and psychological 
trauma’ ,(1) and the consequences are often devastating and endur-
ing.(2) Not infrequently head injury leads to a psychiatric consulta-
tion, which will need to take into account the interplay between the 
brain and its injuries as well as the psychodynamic processes that 
follow from the injury.
In the immediate aftermath of the head injury, the management 
rests with the acute surgical and medical team.(3) The psychiatrist 
is usually not involved at this stage. Nevertheless, to understand the 
later neuropsychiatric effects of head injury it is ﬁ  rst necessary to 
know what happens to the brain when it is injured.
Open head injuries
In open head injuries there is penetration of the skull often with 
considerable destruction of brain tissue local to the trauma, but 
relatively less at a distance—particularly for lower velocity injuries

relatively less at a distance—particularly for lower velocity injuries 
such as stabbing. Open head injuries may therefore be associated 
with little, if any, loss of consciousness, which is generally a marker 
of diffuse brain injury.
Closed head injuries
(a) Contusions
In closed head injuries acceleratio n/deceleration forces and shearing
forces damage the brain. The soft brain moves within its hard bony 
box and is damaged. Contusion of the brain occurs, ranging from 
slight localized small vessel bleeding into surrounding tissue to 
almost complete local destruction of the brain.
The medial orbital frontal cortex and the tips and undersurface 
of the temporal lobes are particularly vulnerable to contusions 
(Fig. 4.1.10.1). The brain becomes traumatized on adjacent bone 
of the ﬂ  oor of the skull. Contrecoup localization of contusions is 
sometimes evident.
(b) Intracerebral haemorrhage

Localized haemorrhage into the brain occurs at the site of a contu-
sion. Scattered intracerebral haemorrhages found at the interface 
between grey and white matter are thought to be associated with 
diffuse axonal injury (see below). A large isolated haematoma sug-
gests that a blood vessel has ruptured.
In very severe injury haemorrhages are also found round the 
aqueduct in the brainstem, perhaps caused by distortion of the 
brainstem as a result of cerebral herniation into the posterior fossa 
due to raised intracranial pressure. They are associated with pro-
longed coma or death.
(c) Extradural and subdural haemorrhage
Haemorrhage into the extradural or subdural space will act as a 
space-occupying lesion and contribute to raised intracranial pres-

sure. The extradural haemorrhage, being under high pressure, can rapidly cause coma and death. The patient may ‘talk and die’ , 
regaining consciousness after the head injury, only to lapse a few 
hours later into severe coma. Without acute neurosurgical inter-
vention to drain the blood these patients will die.
Subdural haematomas tend to run a subacute course and as such 
are of more interest to the psychiatrist. They may present with a 
failure to improve, or ﬂ  uctuating drowsiness, weeks or months 
after the head injury. They may regress spontaneously or may 
require surgical drainage, but they do have a propensity to recur.
(d) Diffuse axonal injury
Diffuse axonal injury occurs in the white matter tracts of the 
cerebral hemispheres, including the corpus callosum, and the

cerebral hemispheres, including the corpus callosum, and the 
brainstem, particularly the cerebellar peduncles. Axons break up 
over the course of the ﬁ  rst 24 to 48 h following brain trauma with 
the formation of ‘retraction balls’-globular structures at the end of 
transected axons.(4)
(e) Oedema and ischaemia
Oedema of damaged brain occurs over the ﬁ  rst few hours follow-
ing brain injury. The resulting raised intracranial pressure compro-
mises the cerebral circulation and results in ischaemia, which may 
further contribute to brain injury. Cerebral oedema tends to resolve 
over the course of a few days or weeks.
(f) Neuronal death
Two fairly distinct processes result in neuronal death from 
traumatic brain injury.(4) Necrotic cell death occurs when there is 
massive cell disruption either from the direct effects of the trauma

massive cell disruption either from the direct effects of the trauma 
on the cell membrane or from anoxia. It is a relatively passive pro-
cess though may involve toxic effects of high levels of intracellular 
calcium, excitatory transmitters, and free radicals. On the other 
hand apoptotic cell death, ‘cell suicide’ , is a more active process 
triggered by various routes including ligand binding to cell death 
receptors. These activate, for example, endonucleases which attack 
cellular DNA. Markers of apoptotic cell death are elevated in the 
days and weeks after injury.
Fig. 4.1.10.1 A composite of the contusions found in 50 cases of people dying 
from head injury. (Reproduced with permission from Courville, C.B. (1937). 
Pathology of the central nervous system , Part IV. Paciﬁ  c Press, Mountain View, CA)4.1.10 the neuropsychiatry of head injury

SECTION 4  clinical syndromes of adult psychiatry 388
(g) Late effects
Ventriculomegaly may develop over the weeks and months follow-
ing injury. Often it is the result of atrophy of the white matter of the cerebral hemispheres, usually attributed to diffuse axonal injury, and is associated with atrophy of the corpus callosum. More local-ized atrophy is observed when contusions resolve to leave a loss of brain tissue.
Of greater importance is hydrocephalus resulting from the 
residual effects of subarachnoid blood interfering with the normal cerebrospinal ﬂ  uid ﬂ  ow and preventing it from escaping into the 
venous system. This may require insertion of a ventriculo-pe ritoneal 
shunt to prevent deterioration in cognitive function.
Fractures to the ﬂ  oor of the skull, particularly if they are associated 
with cerebrospinal ﬂ  uid leaks, may allow infection into the sub-

arachnoid space, causing meningitis sometimes years after injury. Cerebral abscesses may take months before they become clinically evident.
Loss of consciousness following head injury
The mechanism of loss of consciousness after mild blows to thehead is poorly understood. Based on animal work some researchers suggest it is produced by activation of cholinergic nuclei inthe pons.
(5)
Loss of consciousness lasting for more than a few minutes is 
likely to damage either cortical areas necessary for consciousness or the subcortical arousal systems. Raised intracranial pressure, partly as a result of compromising cerebral circulation, causes coma. Large or multiple haematomas are likely to be associated with a period of coma, particularly if they are associated with cerebral oedema.

Some patients, however, show prolonged coma with little
to be found on brain scan apart from some evidence ofgeneralized cerebral oedema. In these patients, diffuse axonalinjury may be the cause of their coma, possibly by damaging the white matter tracts that carry arousal signals from the brainstemto the cortex.
Remember that the head injury may have been caused by an 
accident triggered by a loss of consciousness, for example, due to 
hypoglycaemia, alcohol intoxication, or an epileptic ﬁ  t. Systemic 
effects (e.g. hypoxaemia or fat emboli) may exacerbate uncon-
sciousness due to head trauma, as may drug intoxication.
Head injury severity
It is surprisingly difﬁ  cult to predict the degree of brain injury from 
the size of the blow to the head. Some patients after a severe blow to 
the head sustain little injury to the brain. Others will suffer severe 
brain injury associated with prolonged unconsciousness, merely as

brain injury associated with prolonged unconsciousness, merely as 
a result of hitting their head on the ground by falling over from the 
standing position. Perhaps in the very occasional case signiﬁ  cant 
brain injury occurs when there is no, or only momentary, loss of consciousness (see post-concussion syndrome below). The pres-ence of a skull fracture says little about the severity of the brain injury incurred.
There are several clinical indicators of head injury severity 
(Box 4.1.10.1). Of these the duration of retrograde amnesia 
is probably the least valuable: it correlates very poorly with head injury severity.The duration of post-traumatic amnesia is probably the best 
marker of outcome,
(6) and is particularly useful because it can be

(6) and is particularly useful because it can be 
assessed retrospectively. Most patients with a post-traumatic amnesia of less than 1 week will be left with little if any disability, while a duration of more than 1 month indicates that there is likely to be enduring and signiﬁ  cant disability.
Predictors of a worse outcome after head injury are a previous
head injury, older age, APOE e4  positive status, and alcohol
dependence.
There is no universally accepted classiﬁ  cation of head injury severity. 
However, the most widely used grading system is based on the lowest rating of the Glasgow Coma Scale ( GCS )
(7) following injury.
X Mild: GCS score 13 to 15. Likely to be associated with a loss of 
consciousness of less than 30 min and a post-traumatic amnesia of less than 24 h. There must be clinical evidence of concussion.
X Moderate: GCS score 9 to 12. Likely to be associated with a loss

X Moderate: GCS score 9 to 12. Likely to be associated with a loss 
of consciousness of more than a few minutes but less than 6 h and a post-traumatic amnesia of more than 1 day but less than 2 weeks.
X Severe: GCS score 3 to 8. Likely to be associated with a loss of 
consciousness of more than 6 h or a post-traumatic amnesia of more than 2 weeks.
On average 200–300/100 000 population attend hospital with a head injury every year.
(8) About one-sixth of those attending 
hospital will be admitted. This reﬂ  ects the fact that about 80 per cent 
of head injuries are mild, 10 per cent moderate, and 10 per cent severe.
At greatest risk are 15- to 25-year-olds. The sex ratio is about two 
to three males to one female. Risk factors include alcohol misuse as well as lower socio-economic class. Road trafﬁ  c accidents are the

to three males to one female. Risk factors include alcohol misuse as well as lower socio-economic class. Road trafﬁ  c accidents are the 
largest single cause of head injury in most civilian cohorts, followed by assaults and falls. A signiﬁ  cant proportion will sustain their head 
injury as a result of deliberate self-harm.Box 4.1.10.1 Clinical indicators of head injury severity
X The duration of retrograde amnesia—the period leading up to 
the injury for which memories have been lost. T ends to shrink as the patient recovers.
X The depth of unconsciousness as assessed by the worst score 
on the Glasgow Coma Scale—a score of 3 indicates absent responses with severe coma, 15 is normal consciousness.
X The duration of coma—this may be difﬁ  cult to ascertain 
because of routine sedation and ventilation following severe head injuries.
X Neurological evidence of cerebral injury—abnormality on 
neuroimaging or EEG.
X The duration of post-traumatic amnesia—interval between

X The duration of post-traumatic amnesia—interval between 
injury and the return of normal day-to-day memories.

389
The prevalence rate for those experiencing considerable disability 
as a result of head injury is in the order of 100 per 100 000.
Neuroimaging
In the emergency room or on the trauma unit CT brain scanning is generally the preferred investigation, with its faster acquisition time and good visualization of subdural and extradural haematomas.
For later neuropsychiatric assessment magnetic resonance imag-
ing (MRI) is preferred.
(9) Cerebral contusions are often found near 
the bone–brain interface (see above) where the image quality of CT is reduced because of imaging artefacts from the adjacent bone. MRI has no such limitation and generally has better sensitivity and anatomical deﬁ  nition. MRI is able to detect, on T
2-weighted images,

2-weighted images, 
changes in signal associated with a diffuse axonal injury when the white matter would have appeared normal on CT brain imaging. Gradient echo MRI sequences should be performed to detect haemosiderin deposits from old small traumatic haemorrhages.
Despite its greater sensitivity a normal MRI does not rule out 
signiﬁ  cant brain injury. On the other hand, particularly in the 
elderly, MRI may detect abnormalities unrelated to the head injury. It may not be possible to perform an MRI scan if there is magnetic material present in the body (e.g. a pacemaker).
The MRI scan can be normal and yet functional imaging of cere-
bral metabolism using single-photon emission computed tomog-raphy or positron-emission tomography will detect abnormalities. In general, changes on functional imaging correlate better with 
neuropsychological test performance than do lesions found on 
structural imaging.
(10) However, abnormalities on functional imag-

ing are not necessarily due to brain injury. Hypometabolism may be seen in mental illness without brain injury, for example in depression. Marked hypometabolism on positron-emission tomog-
raphy imaging has been observed in a man with cognitive impair-
ment occurring immediately after a psychological trauma.
(11)
He had sustained no head injury.
Electroencephalography
Electroencephalography (EEG) may be useful in the investigation 
of a deteriorating conscious level or unexpectedly prolonged unconsciousness, and in the investigation of unusual behavioural disturbances that may be attributable to epilepsy. However, EEG is not a good predictor of post-traumatic epilepsy and is generally not useful as a guide to prognosis.
Neuropsychological assessment

A neuropsychological assessment is an invaluable accompaniment to the psychiatric history and examination, and good liaison with the neuropsychologist is essential. Areas of impaired performance can be documented and quantiﬁ  ed. This is often useful as a base-
line for future assessments and to guide rehabilitation.
The National Adult Reading T est, for people whose ﬁ  rst language 
is English, gives a good estimate of pre-injury IQ.
(12) This can then 
be compared with the present performance on cognitive testing, to estimate the impairment produced by the head injury.
Subtle neuropsychological impairments, which are often not 
obvious clinically, suggest that the patient may have more problems when they return to work than would otherwise have been expected. On the other hand, if there is clinical evidence ofunderperformance, and yet standard neuropsychological test

results are normal, then it is particularly important that executive function is tested.
(13)
Function and health
Psychological symptoms far outstrip neurophysical symptoms (e.g. hemiparesis or dysarthria) as determinants of chronic disabil-ity and suffering, both of the patient and their carer, following brain injury.
The ideas encapsulated in the International Classiﬁ  cation of 
Functioning, Disability and Health (ICF) (http://www3.who.int/icf/icftemplate.cfm) are important for understanding recovery from brain injury. ICF is so named because it wishes to emphasize health and functioning by moving away from a dichotomous distinction between those who are healthy and those who are disabled. ICF is a development of the earlier classiﬁ  cation ICIDH 
based on:
X Impairments—abnormalities of structure, or physiological or 
psychological function.
X Disability—concerned with performance of activities.
X Handicap—reﬂ  ects limitations fulﬁ  lling the person’s normal

X Handicap—reﬂ  ects limitations fulﬁ  lling the person’s normal 
social role and participation in society. It is very responsive to external, e.g. environmental and societal, factors.
In ICF an individual’s position on the spectrum between health 
and disability is considered according to (i) functioning and dis-ability and (ii) contextual factors. ICF details the environmental impacts on functioning, e.g. the consequences of living in an area prone to ﬂ  ooding in somebody who is wheelchair dependent. What 
a person can do in a standard environment (their capacity) is dis-tinguished from what they actually do in their usual environment (their performance).
Recovery and long-term outcome from 
head injury
Most recovery takes place in the ﬁ  rst year. As a general rule, the

Most recovery takes place in the ﬁ  rst year. As a general rule, the 
milder the head injury the sooner the patient achieves the asymp-tote of their recovery curve. After a mild head injury most patients will have fully recovered within 6 months. After very severe injury signiﬁ  cant further improvements in impairment may be seen after 
the ﬁ  rst year post-injury. Neuropsychological impairments tend to 
continue improving after neurophysical impairments are static. Nevertheless most of the recovery of cognitive function occurs within the ﬁ  rst year.
(14) Psychiatric symptoms, with their multifac-
torial aetiology, generally show no simple pattern of recovery.
Improvement in functioning and participation may continue 
long after the recovery of the underlying impairment has stopped. These further improvements often reﬂ  ect improved coping strate-

gies and environmental measures to facilitate independence. This will be the focus of the community rehabilitation team as they attempt to help minimize handicap, for example by improving access to local shops. Memory aids may enable the person to return to work. Continuing improvements in participation in social life and work can take place 5 to 10 years after head injury.
(15)
But sometimes early gains are made, for example as a result of 
being in a return-to-work rehabilitation programme, which are subsequently lost over the longer term. In one study,
(16) 25 per cent 4.1.10 the neuropsychiatry of head injury

SECTION 4  clinical syndromes of adult psychiatry 390
had deteriorated at 5 years follow-up, with a similar proportion 
improving compared with how they were at 6 months. Those who deteriorated were more depressed and anxious, had lower self-esteem and had more problems with alcohol than those who improved.
In the longer term, decades after injury, it has been suggested 
that the reduced reserve of the injured brain makes it particularly vulnerable to the effects of ageing. Some studies have found an accelerated cognitive decline compared with age matched controls, for example in head-injured soldiers 25 years later.
(17) Head injury 
may be a risk factor for the development of Alzheimer’s disease, particularly in men.
(18) However the evidence, both for an acceler-
ated cognitive decline and for an increased risk of Alzheimer’s disease, is inconsistent.
Aetiology of psychological sequelae

T o understand the mental symptoms that follow head injury it is necessary to know about the person who has been injured, what brain injuries they sustained, and the consequences. However, the interaction between these is complex and poorly understood.
Pre-traumatic factors
People who take risks or get into ﬁ  ghts are more likely to sustain a 
head injury; therefore these personality traits, present before injury, are over-represented in head-injury survivors. Y oung men are at high risk, as are those who have already had a head injury or have cognitive dysfunction.
(19)
The poor social adjustment of many patients before the head

(19)
The poor social adjustment of many patients before the head 
injury partly explains why so many run into behavioural problems afterwards. But premorbid characteristics do not strongly predict who will develop emotional and behavioural problems. Nevertheless, traumatic brain injury probably has the potential to 
turn pre-injury personality traits into post-injury personality 
The trauma
The extent of brain injury probably explains less than 10 per cent of the variance in the amount of psychiatric morbidity that follows brain injury.
(20) In general, early psychiatric symptoms, within 
weeks and months of the injury, correlate better with the extent and location of brain injury than do late psychiatric symptoms. Left hemisphere damage seems to be associated with greater psy-chiatric morbidity. Speciﬁ  c relationships between the location of 
brain injury and the psychiatric symptoms are discussed below.
But the head injury is also a psychological trauma. Amnesia for

But the head injury is also a psychological trauma. Amnesia for 
the event, as a result of the head injury, protects against post-traumatic stress disorder. However, it is a mistake to believe that amnesia for the event prevents a psychological stress reaction to the event itself.
X The meaning of the event may be distressing to the patient.(21)
In the case of assaults, the head injury may signal the potential for further assaults. An accident may have been life-threatening and a shocking reminder to the patient that they are mortal. They may feel aggrieved by an employer’s negligent action that caused the accident.
X The patient may be amnesic for the event, lacking explicit mem-
ories of what happened, but retain implicit memory of what happened. The consequences of these implicit memories may be 
akin to that observed in one of Claperède’s amnesic patients.(22)

The doctor shook the patient’s hand, pricking it while doing so with a concealed drawing pin. The next day the patient could not remember having met the doctor, but ﬂ  inched from shaking his 
hand when it was offered.
X They may have islets of intact memories that may be extremely 
frightening.(23)
Post-traumatic factors
Post-traumatic factors deserve special attention because they are most likely to be amenable to intervention. The psychiatrist needs to consider the patient’s reaction to any disability, as well as the consequences of the disability on the role of the patient in the fam-ily and society. There may be reinforcing cycles of maladaptive behaviour, and compensation claims may complicate the picture.

Cognitive impairment correlates with measures of head injury severity better than any of the other mental sequelae. For example, there is a strong correlation between the duration of post-traumatic amnesia and the severity of cognitive impairment.
Non-speciﬁ  c cognitive impairments include slowness and reduced 
concentration. The severely injured patient is likely to be stimulus bound, i.e. responding to each and every stimulus they are exposed to in a rather concrete way. At the same time they may show perse-veration, with previous responses inappropriately interfering with the answers to subsequent questions, or when the topic of a conver-sation has been changed.
Dysexecutive syndrome
More speciﬁ  c impairments, generally referred to as the dysexecu-
tive syndrome, result from a disturbance of the executive system responsible for organizing, planning, scheduling, prioritizing, and monitoring cognitive activities.

(24) In some patients with isolated 
medial orbito-frontal lesions or dorso-lateral prefrontal lesions, the dysexecutive syndrome may stand alone. Disturbance of the execu-tive system also results in difﬁ  culties in attending to two things at 
once, and distractibility.
Patients with the dysexecutive syndrome may be much more

Patients with the dysexecutive syndrome may be much more 
impaired in everyday life than is predicted by their performance on standard neuropsychological tests. They can manage with the clear instructions of the well-structured and constrained test situation. But in the real world these are absent; priorities have to be set, a strategy planned, decisions taken, and the unexpected dealt with, all without guidance. In the real world, impairment of the executive system may be catastrophic. T ests of the dysexecutive syndrome have been developed in order to be better predictors of these real-
life problems. 
(13)
Memory impairment
Memory impairment is perhaps the most common cognitive impairment that follows head injury, and can be very disabling.
(25)
People will have problems remembering where they put things, what to do next, how to get home from the shops, or what they did

391
yesterday. Anterograde amnesia refers to these enduring problems 
laying down new memories, and must be distinguished from retro-grade and post-traumatic amnesia (see Box 4.1.10.1).
No consistent pattern of brain injury is associated with antero-
grade amnesia and it seems likely that it is the combined damage to several areas which causes the amnesia. Frontal injury may be particularly implicated perhaps by interfering with the executive processes required for normal memory, for example in memory retrieval. As with most amnesic states the amnesia following brain injury is for explicit memories, namely those which are consciously remembered. Implicit memory, for example remembering and learning a motor skill, is relatively well preserved.
Anterograde amnesia is often characterized by distortions and 
inaccurate recall with poor monitoring and insight. Confabulations are often seen.
Communication

Dysphasia is quite common after head injury, and may be rather different from that seen after stroke. The more diffuse and wide-spread injury of traumatic brain injury results in additional cogni-tive impairments which colour the picture. Monitoring of language errors is often particularly poor and the patient may demonstrate a jargon aphasia such that they are apparently unaware that their speech is completely incomprehensible. Dysphasia often continues to improve even many years post-injury.
(26)
Dysprosody, in which the normal rhythms and intonations of 
speech are lost, is also seen, more so after right hemisphere damage. This interferes with social communication because the voice sounds ﬂ at and fails to convey emotion. Social communication is disrupted

for other reasons, for example the patient fails in the turn-taking necessary for normal conversation. Word-ﬁ  nding difﬁ  culties are 
common.
Visuospatial impairments
Visuospatial impairments may contribute to spatial disorientation. Visual agnosia is easy to miss in someone with quite widespread cognitive impairments. Hemi-neglect can be troublesome.
Personality change
Personality change after head injury results in more suffering than any other single sequel.
(27,28)  In general, personality change goes 
hand in hand with cognitive impairment. However, a severe per-sonality change is occasionally found in somebody with almost no impairment of cognitive function. Normal test scores for memory and intellect do not rule out brain injury as a cause of personality change after head injury.
Aetiology

Aetiology
It is not easy to predict who will develop a change in personality after head injury. Sometimes a personality trait present before the injury becomes much more troublesome, but often there is no obvi-ous predisposition. The site of the brain injury may play a role.
(29)
Lesions of the medial and lateral surfaces of the frontal lobe can produce impairments of drive. Whereas orbito-frontal lesions, on the undersurface of the frontal lobe, may cause a more troublesome personality change with impairments in social behaviour.
Post-traumatic factors also need to be considered. Some patients 
seem to learn maladaptive patterns of behaviour; for example the response of the carers may unwittingly reinforce unwanted behav-
iours. Chronic mental illness, aggravated by chronic psychosocial stressors, may be manifest as personality change. Dependence on drugs, particularly alcohol, frequently confounds the picture.
Characteristics of the personality change

Changes in personality(27) include apathy and impairment of moti-
vation and ambition. Patients are often described as childish; this covers a range of traits including impulsivity, poor tolerance of frustration, being demanding and self-centred, and generally lack-ing the ability to take on the adult role in terms of independent decision-making. Patients may be fatuous and facetious. Antisocial behaviours (see below) and disinhibition are severe handicaps that make integration back into the community difﬁ  cult. Sexual disin-
hibition of any type is particularly worrisome. A spectrum of sever-ity is seen, ranging from being inappropriately ﬂ  irtatious through 
to indiscriminate sexual assaults. Head injury is probably a risk fac-tor for borderline personality disorder.
(30)
In acquired antisocial personality disorder the person is often

(30)
In acquired antisocial personality disorder the person is often 
self-centred and relatively oblivious to the needs of others. They are likely to be tactless and, on occasion, offensively rude. Irritability and aggression and impulsive behaviour are seen. They may show a lack of remorse for violent behaviour. These personality traits often are accompanied by the dysexecutive syndrome. Thus not only does the person show disturbed social decision-making, resulting in antisocial behaviours, but also disruption of the planning and organizational skills needed for cognitive tasks. For example, helpful and supportive friends may be alienated in favour of dis-reputable acquaintances, at the same time as money is impulsively spent and lost, on risky projects without any attempt to weigh up the options.
Effects on family and carers

Families ﬁ  nd personality change particularly difﬁ  cult to cope 
with.(31) Children may be ignored and the partner’s needs, particu-
larly emotional needs, forgotten. The healthy balance of the rela-tionship with the partner may be destroyed, with the head-injured person now unable to take an effective part in the household. The partner becomes a carer and the change in roles may have a serious impact on the sexual relationship. Divorce not infrequently follows. However, parents may ﬁ  nd the childish personality of the brain-
injured person easier to cope with; they revert to taking on the parental role.
Personality change may deteriorate. Supportive social networks 
are lost and social isolation and ﬁ  nancial problems may contribute 
to depression or alcohol abuse, which then cause a deterioration in the behavioural problems associated with the personality change. Follow-up studies lend some support to this argument. Some

to depression or alcohol abuse, which then cause a deterioration in the behavioural problems associated with the personality change. Follow-up studies lend some support to this argument. Some 
behavioural problems are found to have deteriorated at 5 years 
after head injury,
(32) and family burden increases over this period.
Early mental symptoms following 
brain injury
On recovery of consciousness many patients after a severe head 
injury go through a period of delirium with clouding of conscious-ness. The clouding of consciousness may resolve, leaving a confu-sional state in clear consciousness with disorientation and thought 4.1.10 the neuropsychiatry of head injury

SECTION 4  clinical syndromes of adult psychiatry 392
disorder consisting of muddled thinking, rambling talk, and
perseverations. This state is often dominated by misperceptions and misrecollections as the patient ﬂ  its from one false observation 
to another.
(33) Fear is common.
Distortions of memory
Confabulations, brief-lived false memories, emerge at about this time. Confabulations occur particularly in association with memory disturbance associated with frontal injury. The patient almost invariably shows poor insight into their memory problems, and is likely to be disorientated.
Occasionally after a severe head injury there are islets of memory

Occasionally after a severe head injury there are islets of memory 
in the dense amnesic period immediately around the time of the injury. These may be recollections of something that was con-sciously experienced at the time. On the other hand, the memories may have been fabricated from information subsequently given to the patient about what happened, or the memories may have no basis in reality and be properly described as a delusional memory.
Alterations of mood and perception
In the early recovery period oneroid states may be seen. The patient may be perplexed. He or she may feel that the trauma never occurred and that the whole event, including being in hospital, is a fabrication. Derealization/depersonalization may be associated with prominent anxiety, with the patient constantly asking for reas-surance. Agitation occurs in about 10 per cent of patients with severe brain injury.
(34)
Hallucinations, particularly visual, are occasionally observed,

(34)
Hallucinations, particularly visual, are occasionally observed, 
whereas illusions of familiarity are quite common after brain injury. The patient may have a sense of déja vu , or that he or she has met 
clinical staff or patients before. Distortions of the sense of familiarity seem to be implicated in many of the delusions observed early after brain injury.
Apathetic states
In many patients the recovery period lacks the positive features described above and is dominated by an apathetic withdrawn state.
Psychosis after brain injury
Early psychotic symptoms
The vast majority of the delusions and hallucinations occurring during the recovery period will themselves remit spontaneously and not relapse. However, it has been shown that, in some patients who have recovered from these early delusions, amylobarbitone can produce a return of symptoms.
(35) This suggests that general-
ized disturbance of brain function plays an important part in the development of early delusions.

(a) Delusional misidentiﬁ  cation
Delusional misidentiﬁ  cations of place, persons, objects, and events 
may be observed early in the course of recovery. Of these the one that is most pathognomonic of brain injury, and which is also asso-ciated with other causes of organic mental disorder, is reduplicative paramnesia. The term reduplicative paramnesia covers a range of phenomena which involve duplication of events or places. Pick,
(36)
who introduced the term, used it to describe a patient who believed she had visited a duplicate hospital.Delusional disorientation for place may involve the belief that

(36)
who introduced the term, used it to describe a patient who believed she had visited a duplicate hospital.Delusional disorientation for place may involve the belief that 
the current location is a duplicate of the true location or in some way displaced, for example that the hospital is in a different country. The patient may have two incompatible attitudes to orientation; this is sometimes referred to as a double orientation. For example, a patient who lives in Edinburgh acknowledges that he is in a hos-pital in London, but says that his home is just a few yards down the road. A common delusional disorientation is the patient’s belief that they are still at work, despite the fact that they remain in hos-pital recovering from their injuries. Such patients lack insight into 
their injuries and report, for example, that they have been sent to 
complete some work assignment and that staff on the ward are colleagues from work.

Whereas isolated delusional misidentiﬁ  cations of place are rare 
in the absence of manifest organic brain disease, most cases of delusional misidentiﬁ  cation of person (e.g. Capgras syndrome) are 
to be found in schizophrenia. Delusional misidentiﬁ  cations of per-
son may also be observed following brain injury, often alongside a reduplicative paramnesia (see also Chapter 4.4).
Delusional misidentiﬁ  cation syndromes can best be understood as 
the result of an interaction between organic brain disease and psy-chological disorder.
(37) Lesions of the right hemisphere, often in 
combination with frontal injury or more diffuse evidence of brain disease, are particularly associated with delusional misidentiﬁ  cation.
Late psychosis
(a) Schizophrenia-like psychosis
A psychotic illness may develop long after the acute confusional state

A psychotic illness may develop long after the acute confusional state 
has resolved. The patient may develop a typical schizophrenia indis-tinguishable from idiopathic schizophrenia. Would he or she have developed schizophrenia regardless of having had a head injury?
Davison and Bagley, almost 40 years ago,
(38) estimated that 
patients after a head injury had a two- to three-fold increased risk of developing a schizophrenia-like psychosis compared with the general population. But there were large variations in the different studies they examined, and most were cohorts of war veterans who will have suffered open head injuries.
Any apparent association between head injury and schizophrenia

Any apparent association between head injury and schizophrenia 
might be explained by the fact that the period from late teens to early 20s is both the period of greatest risk of head injuries and the time when schizophrenia tends to start. In addition people at risk of schizophrenia may also be at increased risk of suffering a head injury (‘reverse causality’
(39)). Two large studies from Denmark(40)
and Sweden,(41) based on linkage of nation wide hospital case reg-
isters, have shown that there appears to be no elevated risk of being admitted to hospital with a diagnosis of schizophrenia in those who have previously suffered a head injury. However, the second study did suggest that other non-affective psychoses, not diagnosed as schizophrenia, might be more common after a head injury. This ﬁ ts with clinical experience; the patients whose psychosis seems

most convincingly related to their head injury are those with more severe injuries. They would be diagnosed as suffering an organic psychosis, not schizophrenia.
(b) Paranoid psychosis
Paranoid psychoses may emerge after brain injury. Not infrequently this occurs relatively early and in a patient with severe cognitive impairment and personality change. Memory impairment will facilitate the development of persecutory ideas; for example, the

393
patient believes that belongings have been stolen. Persecutory ideas 
or delusions of reference are a fairly common cause of aggression and may be hidden by communication difﬁ  culties.
Mood disorders, including anxiety disorders
The study of depression after head injury raises two fundamental 
questions about the nosological status of depression.(42) First, with 
a severe disability should the belief that life is not worth living be regarded as a symptom of depression or a ‘rational’ reaction to an intolerable predicament? Second, what is one to make of symptoms of apathy or anhedonia when the brain pathways involved in gen-erating spontaneous behaviour or the experience of pleasure have been damaged? Most of the biological symptoms of depression can be produced by brain injury.
The diagnosis of depression therefore relies heavily on identify-

ing a depressive mood. Symptoms like self-deprecation or guilt are also particularly helpful in diagnosis. Estimates of the prevalence of depression after head injury vary, partly because of the lack of uni-formity in deﬁ  ning depression. Perhaps 25 per cent of patients 
meet DSM-IIIR criteria for major depression 1 month after injury.
(43)
A similar rate of depression at 1 year is described in several studies, though perhaps the more conservative ﬁ  gure of 14 per cent
(44) is 
more realistic. Over the ﬁ  rst year many who are initially depressed 
recover, to be replaced by those previously not depressed who become depressed.
Aetiological factors include a personal history of depression,

Aetiological factors include a personal history of depression, 
which is twice as common in those who become depressed, and lack of social support. Depression after head injury interferes with rehabilitation, and is associated with aggression. It may exacerbate cognitive impairment and in some cases produce a pseudodementia.
Emotional lability may occur, particularly after severe head injury, 
and is frequently associated with the presence of depression.
Mania
Manic illness after head injury is much less common than depres-sion. It needs to be distinguished from the neurobehavioural symp-toms of, for example, disinhibition and fatuous behaviour that may follow frontal injury. Mania is particularly associated with aggres-sive and assaultative behaviour following brain injury.
Anxiety disorder
Symptoms of anxiety are common after head injury,(45) particu-

larly in those who have suffered mild injury. Generalized anxiety disorder occurs in perhaps 10–15 per cent of cases.
(46)
Early symptoms may be observed in relation to derealization/
depersonalization symptoms, or perplexity. Early on, the amnesic period surrounding the injury may cause great distress. In the cata-strophic reaction, which is observed in patients with moderate to severe cognitive impairment, sudden distress occurs when they fail to perform a task, or because of their inability to communicate.
Anxiety symptoms, particularly in those with a mild head injury, 
may develop over the weeks and months following a head injury. It is then more likely to be associated with depression, post-concussion syndrome, and with post-traumatic stress disorder. Phobic avoid-ance is seen, for example when there is travel anxiety followinga road trafﬁ  c accident. Apprehension is a common complaint,

perhaps reﬂ  ecting problems caused by cognitive impairments, and the person may be indecisive. Therefore anxiety symptoms may 
emerge on return to work. Anxiety symptoms will be inﬂ  ated in the 
presence of ﬁ  nancial or family stress.
Obsessive–compulsive disorder is recognized sequelae of head 
injury. This may partly reﬂ  ect the inﬂ  exibility and rigidity of the 
brain-injured person, or a response to doubt resulting from mem-ory disorder.
Suicide
The risk of suicide is increased following head injury occurring in about 1 per cent of cases over the ﬁ  rst 15 years or so after injury.
(47)
This represents about a three-fold increase in suicide rate com-
pared with the age matched population rates. There is no evidence of a speciﬁ  c at risk period. At least some of the increased risk is 
probably because those at increased risk of head injury also have a greater risk of suicide. Rates of attempted suicide are increased after head injury.
Agitation and aggression

The psychiatrist is more likely to be asked to advise about the man-agement of agitation and aggression following head injury than any other mental symptom.
Agitation in the early recovery period after severe brain injury 
will generally spontaneously improve over the course of days or weeks.
(34) Early agitation may be followed by more intractable 
aggressive behaviour.(48) A major predictor of aggression is antiso-
cial behaviour before the head injury.
If the aggressive behaviour emerges early, namely during the

If the aggressive behaviour emerges early, namely during the 
confusional state or shortly after it resolves, then this suggest that the aetiology is largely organic. A pattern of aggression that is highly stereotyped, or erupts over seconds with no or trivial triggers, or is bizarre, and is against a background of calm behaviour, suggests the possibility of epilepsy.
Other causes need to be considered. It is important to rule out 
any medical or surgical complications of the head injury, for exam-ple a subdural haematoma. Likewise pain and sources of infection, for example a UTI. The patient’s worries and fears need to be explored, and phobic anxiety disorder considered. Drugs may make agitation worse and paradoxical effects of sedative medication 
occur if the medication increases confusion or disinhibition, or

occur if the medication increases confusion or disinhibition, or 
results in akathisia. The patient may be in a withdrawal state having stopped a drug they were taking regularly before the head injury. Drug and alcohol dependence may be especially problematic. Symptoms of mental illness may not be immediately obvious because of communication difﬁ  culties. It is therefore necessary to 
search for evidence of persecutory delusions, mania, depression, and anxiety. Any mental illness should be treated before consider-ing medication speciﬁ  cally to treat agitation (see below).
Alcohol and head injury
Alcohol dependence complicates the management of the head-
injured person several-fold. The person may have suffered several previous head injuries, as well as the effects of alcoholic brain dam-age before the head injury. A blow to the head may result in much greater brain injury for reasons that are poorly understood.
(49)

(49)
Poor physical health is likely to prejudice immediate management after the head injury. Subdural haematomas may be problematic. 4.1.10 the neuropsychiatry of head injury

SECTION 4  clinical syndromes of adult psychiatry 394
Alcohol craving may interfere with medical care and rehabilita-
tion.(50) Social networks are often poor, thus complicating
discharge from hospital.
Very occasionally a head injury seems to cure the alcohol depen-
dence. Unfortunately alcohol dependence often gets worse, perhaps because the head injury has weakened impulse control. Indeed some patients develop alcohol dependence when they ﬁ  nd that 
alcohol relieves their anxiety symptoms.
Post-concussion syndrome
The post-concussion syndrome is poorly deﬁ  ned.(51) The term is

The post-concussion syndrome is poorly deﬁ  ned.(51) The term is 
perhaps most usefully reserved to describe a constellation of symp-toms that may result in surprisingly severe disability after mild head injury. These symptoms may be observed after moderate and severe head injuries, in which case they are likely to be in the com-pany of other symptoms more readily understood as resulting from brain injury. There is no consistent relationship between the preva-lence of post-concussion symptoms and injury severity.
Phenomenology
Early symptoms tend to have a more neurological ﬂ  avour and

Early symptoms tend to have a more neurological ﬂ  avour and 
include headache, dizziness, and for example diplopia. Mild head injury fairly consistently results, in the immediate aftermath, in impairment of speed of information processing and concentration. Fatigue is also evident from early on, along with symptoms of noise sensitivity. Anxiety, depression, and irritability are common and may appear after a latent period. The symptoms of post-concussion syndrome overlap with those of post-traumatic stress disorder, and chronic fatigue. Other symptoms occasionally reported include tinnitus, unsteadiness, and muscle pain.
In general after a mild to moderate injury symptoms will have 
recovered by 2 to 6 months. But a few patients, sometimes after a latent period, develop persistent symptoms that last for years. Psychological factors are likely to be important in such patients, 
particularly if their injury is mild.
Aetiology
(a) Brain injury

Aetiology
Several observations support the contribution of brain injury, even 
in those with mild injury. Microscopic lesions in the brain have been described at post-mortem, following mild head injury.
(52)
Imaging, particularly functional imaging with single-photon emission CT or positron-emission tomography, may show abnor-malities. Early after mild head injury there is evidence of cerebral dysfunction. One month after a mild head injury patients under-taking a working memory task showed more widespread activation of cerebral cortex compared to controls, even though their actual performance on the task was normal.
(53)
(b) Psychological factors

(53)
Psychosocial factors have also been found to play a part in post-concussion syndrome, more so in those with symptoms lasting longer than 1 year. If the accident occurs at work, particularly if the person blames their employer, symptoms are more likely. A meta-analysis of the effects of compensation on symptoms, any symp-tom, after head injury concluded that, on average, being involved in compensation claims increases symptoms by about 25 per cent.
(54)
This effect was larger in those with milder injuries.(c) Model of interaction
Lishman has proposed a model in which early disturbance of brain function after mild head injury results in the early symptoms of post-concussion syndrome.
(1) In most patients these gradually

(1) In most patients these gradually 
resolve and a good recovery is made. However, the post-concussion syndrome may develop if psychological effects interfere with the normal process of recovery. Anxiety is thought to play a large part in impeding recovery; the patient worries about the symptoms and focuses on them. These may be aggravated if the patient is vulner-able to somatization, or there are compensation issues at stake. The symptoms may cause secondary disability provoking yet more anxiety, which will be made worse if there are additional psychoso-cial stressors. The role of psychological factors is greatest in those with very mild head injuries and very chronic symptoms.
Post-traumatic epilepsy
Early ﬁ  ts, within the ﬁ  rst week, are relatively benign, sensitive to

Early ﬁ  ts, within the ﬁ  rst week, are relatively benign, sensitive to 
prophylactic anti-convulsants, and are only weak predictors of later epilepsy.
Only about 5 per cent of closed head injuries go on to develop 
late seizures, compared with 30 per cent after an open head injury. The majority of these late seizures start in the few years following injury. By the time 5 to 10 years have elapsed without seizures any subsequent seizure development may be unrelated to the head injury.
(55)
The likelihood of developing seizures in patients with a closed 
head injury is increased by the presence of a depressed skull fracture, intracranial haematoma, and early seizure, as well as by the severity of the injury. Mild head injuries result in only a small increased risk of epilepsy above population norms. The EEG is generally not a good predictor of post-traumatic epilepsy.
Post-traumatic epilepsy increases psychiatric morbidity,

Post-traumatic epilepsy increases psychiatric morbidity, 
particularly mood disorders, and may increase the risk of late dementia.
Prophylactic anti-convulsants have no effect on reducing 
the incidence of late post-traumatic epilepsy.
(56) Carbamazepine, 
rather than phenytoin, is the drug of choice if an anti-convulsant is needed because it has less effect on cognition.
(57) Half of all patients 
with post-traumatic epilepsy from open head injuries are found to be in remission by 5 to 10 years.
Head injury in children
Children, compared with adults, are more likely to suffer cerebral oedema and early post-traumatic epilepsy. They tend to develop a relatively stereotyped pattern of changes in personality with emo-tional lability, overactivity, reduced attention span, and irritability with outbursts of temper and rage. Apart from personality changes the commonest psychiatric disorders that follow childhood head injuries are attention-deﬁ  cit hyperactivity disorder, and obsessive–

compulsive disorder.
(58) Children who develop attention-deﬁ  cit 
hyperactivity disorder after head injury tend to demonstrate less hyperactivity than is seen in the idiopathic form.
It is sometimes said that the greater potential for plasticity which 
may be present in the younger person’s brain, results in a better outcome compared to adults. There is some evidence for this for mild and moderate head injuries. However, children with severe head injuries are likely to be left with persistent cognitive deﬁ  cits

395
and behavioural problems. Very young children with severe 
head injury suffer a double hazard(59) with both loss of acquired 
skills and interference with further development. This is often complicated by the fact that many of these children will have demonstrated pre-injury behavioural problems. The quality of parenting has a powerful effect on outcome; those with poor par-enting are much more likely to develop behavioural problems.
(60)
Boxing
In the past, when the average number of career bouts was about 300, 10 to 20 per cent of professional boxers went on to develop a chronic traumatic encephalopathy,
(61) the punch-drunk syndrome. 
However now, with an average boxing career of 13 bouts, cases are much less frequently seen.
(62)
Patients with chronic traumatic encephalopathy suffer damage to

(62)
Patients with chronic traumatic encephalopathy suffer damage to 
the extrapyramidal system as well as cerebellar and pyramidal path-ways. They are slow and ataxic. Cognitive impairment, in particular memory impairment, is a frequent accompaniment and about 50 per cent have dementia. Upper brainstem lesions may explain the neurological symptoms, while cerebral atrophy, white matter changes, and damage to diencephalic structures may account for cognitive changes. Perforation of the septum pellucidum, which separates the two lateral ventricles, is a characteristic ﬁ  nding. APOE e4  status 
increases vulnerability to the punch-drunk syndrome,
(63) and this is 
consistent with the ﬁ  nding that amyloid is often present.
Professional footballers may show evidence of subtle impair-

ments of thinking. This raises the possibility that repeated blows to the head from heading the ball may be sufﬁ  cient to cause slight 
brain injury; but a more likely explanation for any injury is head-to-head contact.
(64)
Management of early neurobehavioural 
problems
Interventions aimed at reducing the risk of enduring post-
concussional symptoms after milder injuries, using brief educa-tional, and supportive therapy in the early days post-injury, have been shown to be effective.
(65)
But there is little evidence to guide the management of behav-
ioural problems and mental symptoms arising in the days and weeks following a more severe brain injury. Such symptoms should be regarded as a ﬂ  ag to indicate the need to check on the progress

ioural problems and mental symptoms arising in the days and weeks following a more severe brain injury. Such symptoms should be regarded as a ﬂ  ag to indicate the need to check on the progress 
of recovery. The history needs to be reviewed, paying attention to the period leading up to injury. The patient will need to be exam-ined physically including a thorough neurological examination and checking for fever. It is essential to document the conscious level and orientation. Routine blood tests should be performed, and blood gases and a chest radiograph considered. Medication needs 
to be scrutinized. A neurological or neurosurgical opinion may be needed with a view to considering neuroimaging or an EEG. 
A lumbar puncture, for example looking for meningitis, should probably not be done without specialist advice.
Causes of deterioration after head injury are listed in Box 4.1.10.2. 
Once these have been excluded then the principle of care should be

Once these have been excluded then the principle of care should be 
to allow recovery to take place in a safe environment, paying atten-tion to the general principles of the care of the delirious or dement-ed patient as indicated. Explanation to the patient and his or her family as to what is happening, is required.Management of late mental sequelae
The reader is referred to Chapter 4.1.14 for many of the manage-ment principles relevant to patients with severe cognitive impair-ment after a head injury.
Psychological interventions
(a) Evidence of effectiveness
A small RCT has shown that cognitive behavioural treatment may be useful in those with persistent post-concussion syndrome.
(66)
Inpatient cognitive rehabilitation is probably needed only in those with more severe injuries.
(46) Community therapy can improve 
handicap.(67) The evidence that behavioural strategies can improve

handicap.(67) The evidence that behavioural strategies can improve 
behavioural problems, particularly aggression, in those with brain injury rests very largely on single case studies
(68) or case series 
showing marked improvement in patients with very long-standing symptoms.
(69)
(b) Principles of management
The ﬁ  rst step, after medical issues ha ve been excluded (Box 4.1.10.2),

(69)
The ﬁ  rst step, after medical issues ha ve been excluded (Box 4.1.10.2), 
is to ensure that the patient has received adequate rehabilitation. In those with severe cognitive impairment once the patient is medi-cally stable appropriate inpatient rehabilitation, perhaps on a locked unit, will probably be required. Problems arise if patients have to be sedated to ensure their safety, and the safety of other patients, while they remain inappropriately in an acute hospital bed. Timely access to rehabilitation is likely to reduce the risk of mental sequelae. Not infrequently psychological problems arise if any part of this process has not gone smoothly, or is perceived to have failed. Education, and access to information, is an important part of the care plan. Good advice on strategies for return to work can be invaluable, and some will require formal vocational reha-bilitation. A social worker should be asked to undertake a commu-

nity care assessment, which may identify the need for respite care 
or modiﬁ  cations to the home.
The management of any mental sequelae rests on a good under-
standing of the severity of the brain injury in order to estimatethe likely contribution of brain damage to the mental sequelae.Box 4.1.10.2  Causes of late deterioration in cognitive function 
after brain injury
Speciﬁ  c
X Subdural haematoma
X Hydrocephalus
X Epilepsy, particularly complex partial status
X Late intracranial infection, including cerebral abscess
Non-speciﬁ  c
X Systemic illness, including fat emboli and pain
X Drug intoxication
X Severe mental illness, in particular depression
X The patient ‘gives up’ as he or she gains insight
X Independent dementing process4.1.10 the neuropsychiatry of head injury

SECTION 4  clinical syndromes of adult psychiatry 396
A neuropsychological assessment, to determine injury severity and 
the pattern of impairments, may be needed. The severity of brain injury will suggest whether a particular symptom is mainly due to brain injury or to psychological processes. The degree of cognitive impairment may indicate whether or not the patient is capable of beneﬁ  ting from certain psychological therapies. Those with less 
severe impairments should be offered CBT as appropriate, for example to treat travel anxiety or depression. In addition, the indi-vidual and their family should have access to support and guidance as they try to adjust to the changes forced on them by the head injury. Sometimes carers or family will need advice on how to man-age challenging behaviours, particularly if their responses seem to be reinforcing the behaviour.
Pharmacological management
By and large patients should be given psychotropics only if absolutely necessary,

(70) attending to the principles described in Box 4.1.10.3 
and avoiding multiple drugs given concurrently. There is an emerging literature on drugs which may enhance cognition.
(71)
(a) Agitation and aggression
Evidence —There are no good trials of medication for agitation 
and aggression after brain injury.(72) Only β-blockers have been 
exposed to randomized controlled trials. These studies showed a slight effect in favour of medication. But despite this β-blockers are 
rarely used in the management of agitation and aggression. In the RCTs very large doses of β-blockers were used that will almost 
inevitably cause worrying side effects in most patients.
Management —Because of the lack of controlled trials, prescrib-

ing for agitation and aggression after brain injury is very much trial and error, requiring good monitoring and documentation of the behaviour. If there is no evidence of beneﬁ  t then the drug should 
be withdrawn and another drug tried. Be wary of responding to every episode of aggression by increasing the dose or adding a new 
drug.
For many psychiatrists, based on little more than anecdotal 
evidence, valproate, or carbamazepine are the drugs of ﬁ  rst choice 
for aggression after brain injury. They have the advantage of anti-convulsant as well as mood-stabilizing effects. Perhaps a third of patients will respond.
Antipsychotics should be used if delusions or persecutory ideas

Antipsychotics should be used if delusions or persecutory ideas 
of reference or fear are also present. But akathisia may perpetuate agitated behaviour which would otherwise have resolved spontane-ously. Atypical antipsychotics, having less risk of motor side effects, are to be recommended.
Antidepressants may be helpful particularly if symptoms of 
anxiety or depression are present. Selective serotonin-reuptake inhibitors should be given in preference to tricyclics. Trazodone given at night may be useful if there is sleep disturbance.
Benzodiazepines should be considered for agitation and
aggression during the early recovery from severe head injury. But be wary of increasing the confusion, and paradoxical violencedue to disinhibition. Because of the potential for addiction,benzodiazepines should not be given to a patient with a chronic aggressive disorder.
(b) Mood disorders and psychosis
Evidence —Good studies evaluating the efﬁ  cacy of medication for

Evidence —Good studies evaluating the efﬁ  cacy of medication for 
depression or psychosis after head injury are lacking.(71)
Management —Depression after a head injury is probably 
more difﬁ  cult to treat than in those without brain injury.(73)
However, some studies in head-injured depressed patients have 
found good response rates. The selection of an antidepressant is no different from that used to treat depression in the absence of brain injury, provided that the principles given in Box 4.1.10.3 are taken into account.
Confabulations and delusions early after brain injury should be 
allowed to resolve spontaneously where possible. For established psychotic symptoms atypical antipsychotics are probably to be recommended.
(c) Apathy

(c) Apathy
Bromocriptine and methylphenidate may be useful for treating apathetic states but controlled trials are lacking. Methylphenidate, with its risk of addiction and troublesome side effects, should only be prescribed if bromocriptine has not been successful, and under consultant supervision.
(d) Drugs which enhance memory and concentration
Evidence —Preliminary evidence supports the use of methylpheni-
date for deﬁ  cits in attention and speed of information processing,(74)
donepezil for attention and memory problems(75) and bromocrip-
tine for executive problems.(76)
Management —There is now a case for considering medication

Management —There is now a case for considering medication 
to enhance cognitive function after brain injury. Drugs are avail-able that may result in small improvements in attention, memory, and executive function. However in almost every case the evidence relies heavily on a single fairly small randomized controlled trial. Longer-term adverse consequences are uncertain. These drugs should only be considered:
X for patients with deﬁ  nite moderate to severe brain injury to 
account for their cognitive complaints,Box 4.1.10.3  Prescribing psychotropics in brain injury
No knee jerk reaction—if possible wait to see if the problem goes 
away spontaneouslySmall doses—start low, go slowOnly continue treatment if good evidence of effectDrug proﬁ  le—choose drugs with less potential for:
X Lowering seizure threshold—avoid clozapine
X Anticholinergic activity—to minimize potential for increasing

X Anticholinergic activity—to minimize potential for increasing 
confusion
X Extrapyramidal side-effects—especially akathisia, parkinson ism, 
and neuroleptic malignant syndrome
X Enzyme induction or other pharmacodynamic interaction 
with other drugs
Regular medication with long-acting anxiolytics, compared with 
short-acting drugs as required, is less likely to produce:
X Withdrawal syndrome
X Development of addiction
X Reinforcement of unwanted behaviour but may produce raised 
blood concentrations

397
X after discussion with the patient and their family about the 
uncertainties of treatment,
X if there is good reason to believe that a small increase in cognitive 
function can result in signiﬁ  cant improvement in handicap,
X with close monitoring of response and side effects.
Insight, capacity, and detention in hospital
Insight and capacity to consent to treatment should be assessed in 
all patients. Lack of awareness of deﬁ  cits is a common problem for 
the head-injured person(77) and affects compliance with, and

the head-injured person(77) and affects compliance with, and 
capacity to consent to treatment. The Mental Capacity Act, 2005 (http://www.opsi.gov.uk/acts/acts2005/20050009.htm or http://www.dca.gov.uk/menincap/legis.htm) governs decision-making on behalf of adults in England and Wales who lack capacity to consent to treatment and manage their affairs. In these patients if there is no family or friend to act on their behalf, an independent advocate may be needed. The clinical team will need to ensure that all rea-sonable measures have been taken to enable the patient to take part in any decision-making. Any decision to act in the patient’s ‘best interests’ should take into account what is known about their pre-vious views and opinions. Very occasionally advance decisions may be in place which dictate how the patient wishes to be treated.

The psychiatrist may be called when the patient demands to leave 
hospital against medical advice. Only the very exceptional patient 
who is demanding to leave hospital following a head injury, and 
who as a result would be putting his or her health severely at risk, will be found to be competent. If they are not, it may be necessary to consider detention under the Mental Health Act, 1983 (England and Wales) or equivalent.
Patients will also need to be assessed to see if they are capable of 
managing their ﬁ  nances and affairs. If they are not, appropriate 
legal arrangements should be made; in the United Kingdom a receiver may need to be appointed to protect their interests. The prospect of compensation should be considered and, if appropriate, they should be enabled to pursue a personal injury claim.
http://www.ninds.nih.gov/disorders/tbi/tbi.htm National Institute 
of Neurological Disorders and Stroke—Traumatic brain injury information page.

http://www.dh.gov.uk/en/Healthcare/NationalServiceFrameworks/Long-
termNeurologicalConditionsNSF/index.htm The National Service Framework on Long term (neurological) conditions. This provides guidance for health and social services on therapy and support for people with long term neurological conditions. The guidance is very relevant to patients with traumatic brain injury.
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4.1.11 Alcohol-related dementia 
(alcohol-induced dementia; alcohol-related brain damage)
Long-term heavy alcohol consumption causes signiﬁ  cant brain 
abnormalities and impairs cognitive functioning. A number of terms have been used to describe these effects, including: ‘alcohol-
related dementia’ , ‘alcohol-induced dementia’ , and ‘alcoholic 
dementia’ .
(1) The more pragmatic umbrella term ‘alcohol-related 
brain damage’ (ARBD) is also used. The literature is beset with limitations, in particular the lack of a diagnostic gold standard, and the difﬁ  culty in making a clinical diagnosis. Many individuals

labelled as having an alcohol-related dementia are, in fact, suffering from the Wernicke–Korsakoff syndrome (WKS).
(2) (This is a spe-
ciﬁ c neuropathological disease caused by thiamine deﬁ  ciency, 
which can occur secondary to alcohol misuse. It is considered in 
Chapter 4.1.12.) When considering the topic of ‘alcohol-related dementia’ it is probably sensible to take a broad clinically-based diagnostic view that includes both WKS and other cases of ‘dementia’ that appear to be alcohol-related.
(3)
Diagnostic criteria
Diagnostic criteria for ‘substance-induced persisting dementia’ are included in DSM-IV
(4) (Table 4.1.11.1), which also states that there 
must be evidence from the history, physical examination, or labo-ratory ﬁ  ndings that the deﬁ  cits are aetiologically related to the per-
sisting effects of substance use (in this case alcohol). No speciﬁ  c 
inclusion criteria are offered to distinguish alcohol-related demen-
tia from other dementias. In ICD-10,

(5) the Korsakoff syndrome is 
listed separately under the amnesic syndrome heading (F10.6) whereas alcohol-induced ‘dementia’ and ‘other persisting cognitive 
impairment’ are included under the ‘residual and late-onset psy-chotic disorder’ category (F10.73 and F10.74 respectively), where diagnostic guidelines can be found.
Diagnostic criteria for establishing a diagnosis of ‘alcohol-related 
dementia’ have been proposed, conceiving it as a spectrum of 
alcohol-related intellectual and neurological syndromes, ranging from moderate deﬁ  cits to the more severe Wernicke–Korsakoff 
syndrome.
(3) ‘Alcohol-related dementia’ is thus deﬁ  ned as a syn-
drome that results from several aetiological mechanisms including the direct neurotoxic effects of alcohol, metabolic dysfunction dur-

ing intoxication and withdrawal, trauma, vascular injury and thia-mine or other nutritional deﬁ  ciencies.
Table 4.1.11.1  DSM-IV diagnostic criteria for substance-induced 
persisting dementia
A. The development of multiple cognitive deﬁ  cits manifested by both
(1)  memory impairment (impaired ability to learn new information or to 
recall previously learned information)
(2)  one (or more) of the following cognitive disturbances:
(a) aphasia (language disturbance)
(b) apraxia (impaired ability to carry out motor activities despite 
intact motor function)
(c) agnosia (failure to recognize or identify objects despite intact 
motor sensory function)
(d) disturbance in executive functioning (i.e. planning, organization, 
sequencing, abstracting)

B. The cognitive deﬁ  cits in criteria A1 and A2 each cause signiﬁ  cant 
impairment in social or occupational functioning and represent a signiﬁ  cant decline from a previous level of functioning.
C. The deﬁ  cits do not occur exclusively during the course of a delirium and 
persist beyond the usual duration of substance intoxication or withdrawal
D. There is evidence from the history, physical examination, or laboratory 
ﬁ  ndings that the deﬁ  cits are aetiologically related to the persisting effects of substance use (e.g. a drug of abuse, a medication)4.1.11 alcohol-related dementia (alcohol-induced dementia; alcohol-related brain damage)

SECTION 4  clinical syndromes of adult psychiatry 400
Prevalence
Adequate epidemiological studies to determine the size of the 
problem have not been carried out. It has been estimatedthat ‘alcohol-related dementia’ accounts for 10 per cent of the dementia population.
(1) Indeed alcohol misuse may contribute
to as many as 21–24 per cent of all cases of cognitive impairmentin mid-adulthood.
(6) The prevalence is likely to be higher in areas 
of socio-economic deprivation, with most cases presentingbetween the ages of 50 and 60 years.
(7) Early onset has been associ-
ated with poorer prognosis and potential for recovery. Recent
evidence suggests that the prevalence of the Wernicke–Korsakoff 
syndrome, caused by thiamine deﬁ  ciency, may be increasing.(8,9)
Early identiﬁ  cation and intervention can help to maximize opti-
mum recovery.
Causal mechanisms
There is no single cause of ‘alcohol-related dementia’ . Individual susceptibility may be inﬂ  uenced by age; age of onset of drinking

There is no single cause of ‘alcohol-related dementia’ . Individual susceptibility may be inﬂ  uenced by age; age of onset of drinking 
and the drinking history; gender; genetic background; family his-tory of alcohol dependence; nutrition; alcohol exposure before birth; and general health status.
(10) Causal mechanisms include: the 
neurotoxic effect of alcohol and its metabolite acetaldehyde; repeat-ed episodes of intoxication and withdrawal; dietary neglect and vitamin deﬁ  ciencies; repeated episodes of head trauma; cerebro-
vascular events; and liver damage. In particular, thiamine depletion, and metabolic factors, such as hypoxia, electrolyte imbalance, and hypoglycaemia, all of which result from acute or chronic intoxica-tion and withdrawal, are important and interrelated. It is difﬁ  cult

to determine the relative contributions of these mechanisms. A number of theories have been advanced by Lishman and others to explain the mechanisms by which chronic alcohol use might lead to dementia.
(1, 6)
X The brain might be vulnerable to both thiamine depletion and 
alcohol neurotoxicity, the former affecting the basal brain regions and the latter both the basal brain and the frontal cortex.
(1)
Individual genetic vulnerability is likely to have a role in inﬂ  u-
encing these processes.
X Wernicke–Korsakoff pathological processes in the basal brain 
have the potential to damage nearby cholinergic fibresprojecting to the cerebral cortex: the so-called cholinergic hypothesis.
(1,6)
X Alcohol-induced brain pathology couples with other pro-
cesses including ‘ageing, trauma, vascular changes, andhepatic dysfunc tion’ leading to cognitive decline: the couplinghypothesis.
(1,6)
X Ethanol stimulates pituitary corticotrophin leading to elevated

(1,6)
X Ethanol stimulates pituitary corticotrophin leading to elevated 
corticosteroid levels and possible injury to the hippocampus.
X Recurrent alcohol withdrawal has been hypothesized to have 
a kindling effect.(11) During alcohol withdrawal there is increased 
N-methyl-d-aspartate (NMDA) function which is postulated to 
lead to increased neuronal excitability and to glutamate-induced neurotoxicity.
(12) The way in which alcohol interferes with 
glutamatergic neurotransmission, especially through the NMDA receptor, is probably central to an understanding of its long-term effects on the brain.
X Alcohol might lead to an accelerated ageing process.Areas of the brain affected
There is evidence that the frontal lobes and sub-cortical areas 
such as the limbic system, the thalamus and the basal forebrain are particularly vulnerable to alcohol-related damage. The cerebel-lum is also vulnerable. Alcohol-related brain changes in the frontal lobes become more prominent with age.

(13) Emotional processing 
is affected by long-standing heavy alcohol use and dependence, and probably reﬂ  ects abnormalities in the limbic system and the frontal 
lobes.
(14) This is manifested as difﬁ  culty with interpreting non-verbal 
emotional cues and recognizing facial expressions of emotion.
Alcohol-related brain damage has been studied using a variety of 
methods, ranging from the neuropathology of the post-mortem alcoholic brain to neuro-imaging techniques focusing on structural, functional and biochemical changes. There is also a considerable neuropsychological literature.
Early neuropathological studies of the alcoholic brain described fairly uniform cerebral atrophy, mainl y over the dorso-lateral frontal 
regions, widened sulci, a narrowed cortical ribbon, and enlarge-ment particularly of the anterior horns of the lateral ventricles.
(1)
The reduction in cerebral volume seen in the alcoholic

(1)
The reduction in cerebral volume seen in the alcoholic 
brain is due mainly to the loss of white matter in the cerebral hemispheres.
(15) The reduced white matter is not related to changes 
in hydration or changes in the chemical structure of the myelin. Selective neuronal loss in the superior frontal cortex was reported in one study
(15) but not conﬁ  rmed in another.(16) However, there is 
evidence that individual neurones are shrunken in regions where neuronal numbers are normal, such as the superior frontal, cingulate, and motor cortices.
(15,16)
Animal research suggests that alcohol has a direct neurotoxic 
effect on the brain. Chronic ingestion of ethanol by well-nourished rats has been shown to be toxic to cholinergic projection neurones
(17)
and to reduce the complexity of dendritic arborization in hippo-campal pyramidal neurones.

(17)
(18) In the former study, transplanta-
tion of cholinergic neurones into the hippocampus and neocortex corrected the cholinergic deﬁ  cits and memory abnormalities. In 
the latter, abstinence led to an increase in dendritic arborization.
Structural neuroimaging
Neuroimaging studies (CT and magnetic resonance imaging (MRI)) have compared recently detoxiﬁ  ed alcoholics without obvi-
ous cognitive impairment with age-matched controls. CT studies conﬁ  rmed diffuse atrophy of brain tissue, with the frontal lobes 
showing most extensive shrinkage.
(19) Follow-up studies showed 
that abstinence was associated with reversibility of brain shrink-age,
(19) particularly in younger individuals and in women.(20)
Structural MRI studies have reported reduced volume of both 
grey and white matter in the cerebral cortex, especially the frontal

grey and white matter in the cerebral cortex, especially the frontal 
lobes, which are used for reasoning, judgement, and problem solving,
(13) particularly in older age groups. Changes have also been 
shown in other structures involved in memory, such as the hippo-campus (in adolescents and adults), mammillary bodies, thalamus and cerebellar cortex.
(21–24)  Other abnormalities include thinning 
of the corpus callosum and reduced volume in the pons.(25)
Reduced white-matter volume is also seen in the temporal lobes(in alcohol dependent subjects with seizures) and in the cerebellar

401
vermis where the loss is associated with deﬁ  cits in postural stability.(26)
More recent MRI studies have not supported the idea of increased 
vulnerability among women. (27) Abstinence is associated with 
recovery of tissue volume.
Functional neuroimaging
Functional neuroimaging studies have reported hypometabolism 
in the frontal and parietal cortices of chronic alcoholics without major neurological impairment, when compared with normal controls.
(28–31) These abnormalities improve following 
abstinence,(31,32) mainly during the 16 to 30 days after the last 
use of alcohol. Metabolic recovery is most marked in the frontal area.
(31)
Proton magnetic resonance spectroscopy can be combined with 
MRI, allowing in vivo  insight into brain metabolism.(33–35)  The 
metabolic changes observed in the few magnetic resonance spec-troscopy studies that have been carried out suggest neuronal loss and compensatory gliosis.
Neuropsychology

Many individuals with a history of chronic excessive alcoholconsumption show evidence of moderate impairment in short- and long-term memory, learning, visuoperceptual abstraction, visuospatial organization, the maintenance of cognitive set,and impulse control.
(36) This tendency for alcoholics to show
proportionally greater visuospatial than language-relatedimpairments suggests that alcohol might have a selective effect on the right hemisphere: the so-called ‘right hemisphere hypothe-sis’ .
(37) However, right hemisphere functions also decline with
ageing and the current  view is that the functional lateralitiesof ‘alcoholics’ and ageing individuals are similar to normalcontrols.
(37)
Neuropsychological performance improves with abstinence.

(37)
Neuropsychological performance improves with abstinence. 
However, impairments can be detected in apparently healthy, abstinent alcohol dependent individuals
(38) and are still detectable 
even after 5 years of abstinence.(39) Performance on neuropsycho-
logical tests has generally been poorly correlated with structural imaging changes,
(19,40) particularly with changes in grey-matter 
volume. However, one MRI study reported signiﬁ  cant correlations 
between cortical (sulcal) and subcortical (ventricular) ﬂ  uid vol-
umes and some cognitive measures.(22) Another study, using a 
combination of structural (CT or MRI) and functional imaging (positron emission tomography) together with neuropsychological tests in older alcohol-dependent patients who were abstinent, found a signiﬁ  cant correlation between degree of atrophy/metabolic

functioning in the cingulate gyrus, and performance on the Wisconsin Card Sort T est.
(41)
Neuropsychological test scores do not predict outcome in 
alcohol-dependent patients.(42, 43)
Difﬁ culties in establishing a diagnosis of alcohol-related dementia/
brain damage mean that it remains an ‘invisible disability’(7),
usually goes unrecognized, and is often masked by other problems such as continuing alcohol consumption and withdrawal,physical ill-health, depression and associated traumatic braindamage.All dementia work-ups should include a history of past and pres-
ent alcohol use, conﬁ  rmed with a collateral history.
(6) Appropriate 
treatment of alcohol withdrawal syndromes, assessment and re-

assessment should be carried out over a two-year period. Ongoing assessment and care planning are important as these patients have the capacity to improve with abstinence. The possibility of Wernicke–Korsakoff pathology in cognitively impaired patients with an alcohol use disorder should prompt swift and appropriatetreatment with parenteral thiamine.
(44) Oral B vitam ins should be 
continued long-term.
The mainstay of long-term treatment in alcohol-related dementia 
is abstinence. This can be facilitated by a supportive non-drinking social network, and cognitive behavioural methods to teach recog-nition of factors that predispose to relapse and alternative coping strategies.
(6) Families and care-givers facilitate success and must be

(6) Families and care-givers facilitate success and must be 
actively educated and supported. A rehabilitation approach to activities of daily living and occupation is also a key factor.
Patients with alcohol-related dementia are younger and more 
physically active than the usual dementia population. They do not ﬁ t neatly into any category of care and are at risk of falling ‘through 
the net’ . Services lack the capacity to manage this population so they are passed between services and ﬁ  nd it difﬁ  cult to access 
specialist assessment or care.
Alcohol-related dementia should be recognized as a preventable condition. However, identiﬁ  cation is hampered by a lack of clarity 
in terminology, and a lack of standardized and specialized screen-ing instruments and assessment procedures.
(45) These individuals 
make repeated use of Accident and Emergency Departments, general medical, and long stay wards. Early identiﬁ  cation would

make repeated use of Accident and Emergency Departments, general medical, and long stay wards. Early identiﬁ  cation would 
reduce their need for these services. Abstinence is the key to recovery. Treatment services should be integrated and ﬂ  exible.
Baddeley, A.D., Kopelman, M/D., Wilson, B.A. (2003). The Handbook of 
Memory Disorders , (2nd edn.) Chichester: John Wiley and Sons Ltd.
Edwards, G., Marshall, E.J., Cook, C.C.H. (2003). The Treatment of Drinking 
Problems: a Guide for the Helping Professions , (4th edn.) Cambridge: 
Cambridge University Press
Lishman, W.A. (1998). Organic Psychiatry .The Psychological Consequences of 
Cerebral Disorder , (3rd edn). Oxford: Blackwell Science.
The National Institute of Alcohol Abuse and Alcoholism website has a 
portal which supports researchers and practitioners searching for 
information relating to alcohol research. It has a number of links to 
other databases: http://etoh.niaaa.nih.gov/

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403
4.1.12 Amnesic syndromes
Amnesic disorders can be broadly classiﬁ  ed across two orthogonal 
dimensions. Along the ﬁ  rst dimension, there can be transient or 
discrete episodes of amnesia as opposed to persistent memory impairment. On the second dimension, memory loss can result from either neurological damage or psychological causation, although admixtures of these factors are, of course, very common. The notion of confabulation has traditionally been associated with amnesic syndromes, particularly the Korsakoff syndrome, although it may have a separate basis, and false memories are now known to arise in a number of different situations. With the advent of drugs purporting to inﬂ  uence memory, there is increasing interest in the 
psychopharmacology of memory disorders. This chapter willconsider ﬁ  ndings from investigations of patients with memory

disorders and a few selected psychopharmacological studies ofrelevance. It will not review the extensive literature on functional imaging in normal subjects.
Transient amnesias
Transient global amnesia
Transient global amnesia (TGA) most commonly occurs in the mid-dle-aged or elderly, more frequently in men, and it results in a period of amnesia lasting several hours. It is characterized by repetitive ques-tioning, and there may be some confusion, but patients do not report any loss of personal identity (they know who they are). It is some-times preceded by headache or nausea, a stressful life event, a medical procedure, or vigorous exercise. Hodges and Ward
(1) found that the

(1) found that the 
mean duration of amnesia was 4 h and the maximum was 12 h. In 25 per cent of their sample, there was a past history of migraine, which was considered to have a possible aetiological role. In a further 7 per cent of the sample, the patients subsequently developed unequivocal features of epilepsy (there had been no focal signs or features of epi-lepsy during the original attack) and the memory loss was therefore attributed, in retrospect, to previously undiagnosed epilepsy. There was no association with either a past history of vascular disease, clini-cal signs suggestive of vascular pathology, or known risk factors for vascular disease. In particular, there was no association with transient ischaemic attacks. In 60 to 70 per cent of the sample, the underlying aetiology was unclear.
More recently, Quinette et al .
(2) reviewed the findings in

(2) reviewed the findings in 
1353 patients reported in the clinical literature since 1956 andtheir own data from 142 patients, seen between 1994 and 2004.In general, the ﬁ  ndings were consistent across the two sources. 
There was no sex bias, and the vast majority of attacks occurred between the ages of 50 and 80 (mean = 60.3 ± 9.6). Most patients 
had a single attack, but the annual rate of recurrence rangedfrom 2.9 per cent to 26.3 per cent (6.3 per cent in their own study). In the literature, the duration of attacks ranged from 15 min to 24 h and, in their own investigation, the range was 30 min to 16 h (mean = 5.6 h). These authors investigated putative predisposing and precipitating factors in great detail, concluding that TGA may encompass at least three different groups of patients: (i) younger patients with a history of migraine, in whom spreading neuro-

chemical depression may be implicated, (ii) women who have experienced acute emotional or physical stress, and often havea history of anxiety or depression, and (iii) men who, following physical exertion, develop venous congestion in the contextof insufﬁ  cient jugular vein valves and a precipitating Valsalva 
manoeuvre.
In instances of TGA where neuropsychological tests have been 
administered to patients during the acute episode of memory 
loss,
(1,3) the patients show a profound anterograde amnesia, as 
expected, on tests of both verbal and non-verbal memory. However, performance on tests of retrograde memory is variable. Follow-up studies show either complete or almost complete recovery ofmemories, several weeks to months after the acute attack. Ingeneral, retrograde amnesia recovers before anterogradeamnesia; the degree of shrinkage of retrograde amnesia isheterogeneous; and anterograde memory (new learning) recovers gradually.

The general consensus is that the amnesic disorder results from 
transient dysfunction in limbic-hippocampal circuits, crucial to memory formation. Medial temporal abnormalities have been reported bilaterally in terms of single-photon emission CT (SPECT) measures of perfusion, positron emission tomography (PET) meas-ures of metabolism, diffusion weighted imaging (DWI), and small hippocampal cavities on T2 reversed magnetic resonance imaging (MRI) images.
(4,5) In addition, venous duplex sonography has 
shown jugular vein valve insufﬁ  ciency in a proportion of cases.(5)
Transient epileptic amnesia
This term was coined by Kapur,(6) and it refers to the minority of 
patients with transient global amnesia in whom epilepsy appears to be the underlying cause of the syndrome.
(1) Where epilepsy has 
not previously been diagnosed, the main predictive factors for an epileptic aetiology are brief episodes of memory loss (an hour or less) with multiple attacks.

(1) It is important to note that standard 
electroencephalography (EEG) and CT ﬁ  ndings are often normal. 
However, an epileptic basis to the disorder may be revealed on sleep EEG recordings.
(1,7)
Patients with transient epileptic amnesia may show residual 
deﬁ cits in between their attacks, associated with their underlying 
neuropathology. Kopelman et al .(7) found a moderate degree of 
residual anterograde memory impairment in their patient, related to subsequent (unpublished) ﬁ  ndings of small foci of MRI signal alter-
ation and PET hypometabolism bilaterally in the medial temporal lobes. Several authors have reported patients who describe ‘gaps’ in past personal memories, and Manes et al.
(8) have reported dispro-

portionate inter-ictal retrograde amnesia. The latter group also reported abnormal long-term forgetting of verbal material, but whether these gaps in memory result from faulty encoding (because of subclinical ictal activity), impaired consolidation (giving rise to accelerated forgetting), or deﬁ  cits in retrieval remains controversial.
Epilepsy may, of course, give rise to automatisms or post-ictal

Epilepsy may, of course, give rise to automatisms or post-ictal 
confusional states. Where there is an automatism in such circum-stances, there is always bilateral involvement of the limbic struc-tures involved in memory formation, including the hippocampal and parahippocampal structures bilaterally as well as the mesial diencephalon. Consequently, amnesia for the period of automatic behaviour is always present and is usually complete.4.1.12 amnesic syndromes

SECTION 4  clinical syndromes of adult psychiatry 404
Head injury
In head injury, it is important to distinguish between a brief period 
of retrograde amnesia, which may last only a few seconds or min-utes but can be weeks or months, a longer period of post-traumatic amnesia, and islands of preserved memory within the amnesic gap.
(9) Occasionally post-traumatic amnesia may exist without any 
retrograde amnesia, although this is more common in cases ofpenetrating lesions. Sometimes there is a particularly vivid memo-ry for images or sounds occurring immediately before the injury, on regaining consciousness, or during a lucid interval between the injury and the onset of post-traumatic amnesia. These vividºmemories may become the intrusive ﬂ  ashbacks of a post-traumat-
ic stress disorder (PTSD) syndrome.
Post-traumatic amnesia (PTA) is generally assumed to reﬂ  ect the

Post-traumatic amnesia (PTA) is generally assumed to reﬂ  ect the 
degree of underlying diffuse brain pathology, in particular rota-tional forces giving rise to axonal tearing and generalized cognitive impairment. The length of PTA is predictive of eventual cognitive outcome, psychiatric outcome, and social outcome.
(10) However, 
the duration of PTA is often not well documented in medical records, and these relationships are often weaker than is generally assumed. In addition, contusion to the frontal and anterior tempo-ral lobes is a common consequence of head injury. The clinical fea-tures and underlying pathophysiology of head injury have recently been well described elsewhere.
(11)
Post-traumatic amnesia needs to be distinguished from the per-

(11)
sisting anterograde memory impairment, which may be detected on clinical assessment or cognitive testing long after the period of PTA has ended. Moreover, forgetfulness is a common com-plaint within the context of a post-traumatic syndrome, which may include anxiety, irritability, poor concentration, and various somatic complaints. Commonly, these complaints persist long after the settlement of any compensation issues.
(11)
Alcoholic blackouts
Alcoholic blackouts are discrete episodes of memory loss for signiﬁ  cant events, which should not be confused with withdrawal 
seizures or other ictal phenomena. Alcoholic blackouts are associated with severe intoxication, usually in the context of a history ofprolonged alcohol abuse. Goodwin et al.
(12) described two types of 
blackout—the fragmentary  and the en bloc . However, alcohol-induced

blackout—the fragmentary  and the en bloc . However, alcohol-induced 
state-dependent experiences can be viewed as related phenomena, and it has been suggested that the three represent gradations ofalcohol-induced memory impairment. In state-dependent effects, subjects when sober cannot remember events or facts from an epi-sode of intoxication, which they recall easily when they again become intoxicated. In fragmentary blackouts, the subjects are aware of their memory loss on being told later of an event; there are islands of pre-served memory; and the amnesia tends to recover partially through 
time by shrinkage of the amnesic gap. In en bloc  blackouts there is an 
abrupt beginning and end to the period of memory loss, and the lost memories are very seldom recovered. Blackouts may be more com-mon in binge drinkers, because they are related to a high blood alcohol level. Hypoglycaemia may also be a contributory factor, and blackouts

are more common where there is a history of previous head injuries.
After electroconvulsive therapy
This is an iatrogenic form of transient amnesia. Benzodiazepines 
and anticholinergic agents can also give rise to transient memory loss in more moderate form.
(13)Subjects tested within a few hours of electroconvulsive therapy 
(ECT) show a retrograde impairment for information from the preceding 1 to 3 years, a pronounced anterograde memory impair-ment on both recall and recognition memory tasks, and an accel-erated rate of forgetting.
(14) When retested approximately 6 to 
9 months after completion of a course of ECT, memory generally returns to normal on objective tests. However, complaints of mem-ory impairment can persist, and they may be evident three or more years after a course of ECT has been completed.
(15) It seems that 
patients with persistent complaints of memory loss tend to be those who have recovered least well from their depression,
(14,15) although

(14,15) although 
their complaints tend to focus upon the period for which there was an initial retrograde and anterograde amnesia. A recent American study suggested that sine wave stimulation induces cognitive slow-ing in terms of reaction time, and that multiple bilateral ECT administrations can produce impairments in autobiographical memory retrieval 6 months following treatment.
(16)
Verbal memory appears to be particularly sensitive to disruption.

(16)
Verbal memory appears to be particularly sensitive to disruption. 
Unilateral electroconvulsive therapy to the non-dominant hemi-sphere produces considerably less memory impairment than bilat-eral ECT, although it is important to identify the non-dominant hemisphere by a valid procedure. Attempts to minimize memory disruption by either making changes in premedication or the con-comitant administration of other substances—such as glycopyrrolate, physostigmine, thyroxine, dexamethasone, or acetylcholine—have produced limited or no beneﬁ  t.
Post-traumatic stress disorder
This clinically important syndrome is described in Chapter 4.6.2. 
Post-traumatic stress disorder (PTSD) is characterized by vivid, intrusive thoughts and memories (‘ﬂ  ashbacks’), avoidance and

Post-traumatic stress disorder (PTSD) is characterized by vivid, intrusive thoughts and memories (‘ﬂ  ashbacks’), avoidance and 
anxiety phenomena, and hyper-arousal and hyper-vigilance symp-toms. However, there may be instances of brief memory loss, dis-tortions, or even frank confabulations. For example, a victim of the Herald of Free Enterprise  disaster at Zeebruge described trying to 
rescue a close friend still on board the ship, when other witnesses reported that the close friend had, in fact, not been seen by the victim from the moment the ship turned over. Cases of PTSD may, of course, be confounded by other factors, such as head injury. Nevertheless, it is of interest that PTSD symptoms can occur even when a subject is completely amnesic for an episode.
(17) PTSD vic-
tims can show deﬁ  cits in anterograde memory on formal tasks

tims can show deﬁ  cits in anterograde memory on formal tasks 
many years after the original trauma, and there is also evidence that they may show loss of hippocampal volume on magnetic resonance imaging (MRI) brain scan, which has been attributed by some to a surge in glucocorticoid secretion. Brewin
(18) has recently reviewed 
four controversies in autobiographical memory for trauma. He found that qualitative and quantitative differences do exist between trauma and non-trauma memories in PTSD victims, and that memories for trauma can be either better or worse than non-trau-ma memories. In other words, some incidents may be recalledparticularly vividly, and others may be forgotten.
Psychogenic fugue

A fugue state is a syndrome consisting of a sudden loss of all auto-biographical memories and knowledge of personal identity, usually associated with a period of wandering, for which there is asubsequent amnesic gap on recovery. Characteristically, fuguestates last a few hours or days, up to about 3 weeks. There are also

405
descriptions in the literature of persisting autobiographical memo-
ry loss, in which personal identity has been ‘re-learned’ , and these are better known as ‘psychogenic focal retrograde amnesia’ .
(19)
However, whenever such complaints persist, the suspicion of simu-lation must arise. Fugue states differ from transient global amnesia or transient epileptic amnesia in that the subject does not know who he or she is, and repetitive questioning is not a characteristic feature in fugues.
As discussed elsewhere,
(20) fugue states are always preceded by a

(20) fugue states are always preceded by a 
severe precipitating stress. Second, depressed mood is also an extremely common antecedent for a psychogenic fugue state, and may be associated with manifest suicidal ideas just before orfollowing recovery from the fugue. Third, various authors have noted that there is often a past history of a previous transient neu-rological amnesia, such as epilepsy or head injury. In brief, it appears that patients who have experienced a previous transient organic amnesia, and who become depressed and/or suicidal, are particularly likely to go into a fugue in the face of a severe, precipi-tating stress. That stress may consist of marital or emotional dis-cord, bereavement, ﬁ  nancial problems, a criminal charge, or stress 
during wartime. Fugues have been described as a ‘ﬂ  ight from sui-
cide’ . Recent neuro-imaging investigations have examined people 
purportedly in a fugue state with very inconsistent results, probably

purportedly in a fugue state with very inconsistent results, probably 
because the delay until imaging, the imaging techniques employed, and the clinical situations themselves have varied considerably across studies.
Amnesia for offences
This is a phenomenon commonly brought to the attention of psychiatrists, particularly forensic psychiatrists, although the empirical literature on this disorder is scanty. Amnesia is claimed by 25 to 45 per cent of offenders in cases of homicide, approxi-mately 8 per cent of perpetrators of other violent crimes, and a small percentage of non-violent offenders.
(21) It is necessary to

(21) It is necessary to 
exclude underlying neurological or endocrine factors such as an epileptic automatism, post-ictal confusional state, head injury, sleepwalking, or hypoglycaemia. Underlying medical disorder can be grounds for a so-called ‘insane’ automatism in English law (if the result of an internal brain disease) or a ‘sane’ automatism (if the consequence of an external agent), but otherwise amnesia per se does not constitute grounds for alleviation of responsibility for an offence.
Amnesia for an offence is most commonly associated with the 
1 States of either extreme emotional arousal or peri-traumatic dis-
sociation, in which the offence is unpremeditated, and the victim usually a lover, wife, or family member. This is most commonly seen in homicide cases (‘crimes of passion’).
2 Alcohol intoxication (sometimes in association with other

2 Alcohol intoxication (sometimes in association with other 
substances), usually involving very high peak levels (‘alcoholic blackout’), and often a long history of alcohol abuse. The victim is not necessarily related to the offender, and the offence may vary from criminal damage, through assault, to homicide.
3 Florid psychotic states or depressed mood. Occasionally offenders 
describe a delusional account of what has happened, quite at odds with what was seen by other observers, and sometimes resulting in confessions to crimes that the person could not actually have committed (a paramnesia or delusional memory). In many other cases, depressed mood is associated with amnesia for an offence, 
just as it is a common associate of psychogenic fugue.
Pyszora et al.
(22) examined the psychiatric reports of all offenders

(22) examined the psychiatric reports of all offenders 
given a life sentence in England and Wales in 1994, 29 per cent of whom claimed amnesia. Detailed, follow-up reports at 3 years were also examined, and these suggested that approximately one-third of those who had claimed amnesia at trial reported complete recov-ery, one-third showed partial recovery, and one-third reported no change in their amnesias. Only about 2 per cent were thought to have been malingering.
Persistent memory disorder
The amnesic syndrome can be deﬁ  ned as follows:
An abnormal mental state in which memory and learning are affected 
out of all proportion to other cognitive functions in an otherwise alert and responsive patient.
(23)
The Korsakoff syndrome can be deﬁ  ned in the same way but 
with the addition of the following phrase:
 . . . resulting from nutritional depletion, notably thiamine deﬁ  ciency.

(23)
In fact, Victor et al.(23) used the ﬁ  rst description as a deﬁ  nition of 
the Korsakoff syndrome, but it is important to distinguish between amnesic syndromes in general (for which the Victor et al. deﬁ nition 
suffices) and the particular clinical condition described by Korsakoff,
(24) whose cases can all be viewed (with hindsight) as 
having suffered nutritional depletion, whether of alcoholic or non-alcoholic causation. Various disorders can give rise to an amnesic syndrome.
The Korsakoff syndrome
As mentioned, this is the result of nutritional depletion, namely a thiamine deficiency. Korsakoff
(24) described this condition as 
resulting from alcohol abuse or from a number of other causes, but by far the most common nowadays is alcohol abuse.
(a) Clinical

There are frequent misunderstandings about the nature of this dis-order. ‘Short-term memory’ , in the sense that psychologists employ it, is intact but learning over more prolonged periods is severely impaired, and there is usually a retrograde memory loss which characteristically extends back many years or decades.
(20) Korsakoff 
himself noted that his patients ‘reason about everything perfectly well, draw correct deductions from given premises, make witty remarks, play chess or a game of cards, in a word comport them-selves as mentally sound persons’ .
(24) However, he also noted repet-

itive questioning, the extensive nature of the retrograde memory loss, and a particular problem in remembering the temporal sequence of events, associated with severe disorientation in time. As will be discussed below, he gave examples of confabulation reﬂ ecting the problem with the temporal sequence memory, such 
that real memories were jumbled up and retrieved inappropriately, out of temporal context.
Many cases of the Korsakoff syndrome are diagnosed following 
an acute Wernicke encephalopathy, involving confusion, ataxia, nystagmus, and opthalmoplegia. Usually, not all these features are present, and the opthalmoplegia in particular responds rapidly to treatment with high-dose vitamins. These features are often associ-
ated with a peripheral neuropathy. However, the disorder can also 4.1.12 amnesic syndromes

SECTION 4  clinical syndromes of adult psychiatry 406
have an insidious onset, and such cases are more likely to come to 
the attention of psychiatrists; in these cases, there may be either no known history of or only a transient history of Wernicke features. There are also reports that the characteristic Wernicke–Korsakoff neuropathology is found much more commonly at autopsy in alco-holics than the diagnosis is made in life, implying that many cases are being missed.
Victor et al .
(23) reported that 25 per cent of patients with the 
Korsakoff syndrome ‘recover’ , 50 per cent show improvement through time, and 25 per cent remain unchanged. Whilst it is unlike-ly that any established patient shows complete recovery, the present author’s experience is that substantial improvement does occur over a matter of years if the patient remains abstinent. It is probablycorrect to say that 75 per cent of these patients show a variable degree of improvement, whilst 25 per cent show no change.

(20)
(b) Pathology
The characteristic neuropathology in what is often known as the Wernicke–Korsakoff syndrome consists of neuronal loss, micro-haemorrhages, and gliosis in the paraventricular and periaqueductal grey matter.
(23) However, there has been a debate as to which par-
ticular lesions are critical for the manifestation of chronic memory disorder. Victor et al .
(23) pointed out that all 24 of their cases in 
whom the medial dorsal nucleus of the thalamus was affected had a clinical history of persistent memory impairment (Korsakoff syn-drome), whereas ﬁ  ve cases in whom this nucleus was unaffected 
had a history of Wernicke features without any recorded clinical history of subsequent memory disorder. By contrast, the mammil-lary bodies were implicated in all the Wernicke cases, whether or not there was subsequent memory impairment. However, Mair et al .
(25) provided a careful pathological and neuropsychological

(25) provided a careful pathological and neuropsychological 
description of two patients with the Korsakoff syndrome, whose autopsies showed lesions in the mammillary bodies, the midline, and anterior portion of the thalamus, but not in the medial dorsal nuclei. Mayes et al.
(26) obtained very similar ﬁ  ndings in two further 
patients with the Korsakoff syndrome, who had also been very care-fully described both neuropsychologically and at autopsy. Harding et al.
(27) reported that pathology in the anterior principal thalamic 
nuclei was the critical difference between eight patients whosuffered a persistent Korsakoff syndrome, and ﬁ  ve others who expe-
rienced only a transient Wernicke episode. Taken together, these ﬁ ndings suggest that the mammillary bodies, the mammillothalam-
ic tract, and the anterior thalamus may be more important to mem-ory dysfunction than the medial dorsal nucleus of the thalamus.
There is also evidence of general cortical atrophy particularly

There is also evidence of general cortical atrophy particularly 
involving the frontal lobes in patients with the Korsakoff syndrome, and this is associated with neuropsychological evidence of ‘frontal’ or ‘executive’ test dysfunction in these patients.
(20)
There have been a number of neuro-imaging studies of the 
Korsakoff syndrome. CT scan studies indicated a general degree of cortical atrophy, particularly involving the frontal lobes.
(28) MRI 
studies have indicated more specific atrophy in diencephalic structures.
(29) PET investigations show variable ﬁ  ndings, but hypo-
metabolism has been reported in thalamic, orbito-medial frontal, and retrosplenial regions.
(30)
Herpes encephalitis
This can give rise to a particularly severe form of amnesic syn-drome.

(30)
(31) Many cases are said to be primary infections, although others may involve a reactivation of the virus. Characteristically, 
there is a fairly abrupt onset of acute fever, headache, andnausea. There may be behavioural changes. Seizures can occur.The fully developed clinical picture with neck rigidity, vomiting, and motor and sensory deﬁ  cits seldom occurs during the ﬁ  rst
week. Moreover, some cases commence more insidiously with behavioural change or psychiatric phenomena, the confusionand neurological features becoming evident only later. Diagnosisis by the PCR test or a raised titre of antibodies to the virus inthe cerebrospinal ﬂ  uid. A presumptive diagnosis is sometimes

made on the basis of the clinical picture as well as severe signal alteration, haemorrhaging, and atrophy in the temporal lobes on MRI brain imaging.
Neuropathological and neuro-imaging studies usually show 
extensive bilateral temporal lobe damage,
(29,32) although occasion-
ally the changes are surprisingly unilateral. There may be frontal changes, often in the orbito-frontal regions, and there may be focal changes elsewhere as well as a variable degree of general cortical atrophy. The medial temporal lobe structures are usually particularly severely affected, including the hippocampi, amygdalae, entorhinal, and perirhinal cortices, and other parahippocampal structures. Encephalitis, like head injury, can also implicate basal forebrain structures which give cholinergic outputs to the hippocampi; this may further exacerbate the damage.
The chronic memory disorder in herpes encephalitis is often very 
severe,
(31) but it shows many resemblances to that seen in the

severe,
(31) but it shows many resemblances to that seen in the 
Korsakoff syndrome, consistent with the fact that there are many neural connections between the thalami, mammillary bodies, and the hippocampi. Patients with herpes appear to have better ‘insight’ into the nature of their disorder, and a ‘ﬂ  atter’ temporal gradient to 
their retrograde memory loss (i.e. less sparing of early memories), and they may have a particularly severe deﬁ  cit in spatial memory 
when the right hippocampus is involved.
(20) However, the simi-
larities in the episodic memory disorder tend to outweigh the differences.
On the other hand, a more extensive involvement of semantic

On the other hand, a more extensive involvement of semantic 
memory is characteristic in herpes encephalitis, and this results from the widespread involvement of the lateral, inferior, and poste-rior regions of the temporal lobes. Semantic memory refers to a knowledge of facts, concepts, and language (see Chapter 2.5.3). Left temporal lobe pathology in herpes encephalitis commonly gives rise to an impairment in naming, reading (a so-called ‘surface dyslexia’), and other aspects of lexico-semantic memory. Right tem-poral lobe damage may lead to a particularly severe impairment in face recognition memory or knowledge of people.
Severe hypoxia

Severe hypoxia can give rise to an amnesic syndrome following car-bon monoxide poisoning, cardiac and respiratory arrests, or sui-cide attempts by hanging or poisoning with the exhaust gases from a car. Drug overdoses may precipitate prolonged unconsciousness and cerebral hypoxia, and this quite commonly occurs in heroin abusers. Zola–Morgan et al .
(33) described a patient with repeated 
episodes of hypoxia and/or cardiovascular problems who devel-oped a moderately severe anterograde amnesia. At autopsy 6 years later, this patient was shown to have a severe loss ofpyramidal cells in the CA1 region of the hippocampi bilaterally, with the rest of the brain appearing relatively normal. Hippocampal atrophy on MRI has found in hypoxic, amnesic patients,
(29)

407
and also thalamic hypometabolism on FDG–PET scanning.(34)
In brief, the memory disorder is likely to result from a combination 
of hippocampal and thalamic changes, related to the manycommon neural pathways between these two structures.However, Caine and Watson
(35) in an important review reported 
that less than 20 per cent of hypoxic patients described in theliterature show either a speciﬁ  c amnesic syndrome (in the absence 
of other cognitive deficits) or damage solely confined to thehippocampi.
Vascular disorders
Two types of speciﬁ  c vascular lesions can particularly affect memory, 
as opposed to general cognitive functioning, namely thalamic infarction and subarachnoid haemorrhage. However, memory dis-order may be the ﬁ  rst manifestation of the vascular form of ‘mild 
cognitive impairment’ .
In an elegant CT scan study, von Cramon et al.
(36) showed that

(36) showed that 
damage to the anterior thalamus was critical in producing an amnesic syndrome. When the pathology was conﬁ  ned to the more 
posterior regions of the thalamus, memory function was relatively unaffected. The anterior region of the thalamus is variably supplied by the polar or paramedian arteries in different individuals, both of which are, ultimately, branches of the posterior cerebral artery that also supplies the posterior region of the hippocampi. When there is a relatively pure lesion of the anterior thalamus, antero-grade amnesia without an extensive retrograde memory loss com-monly results. However, cases in whom there is also retrograde memory loss, or even a generalized dementia, have been described following thalamic infarction, and this presumably relates to the extent to which thalamic projections are also implicated in the infarction.

Subarachnoid haemorrhage following rupture of a berry aneu-
rysm can result in memory impairment, whether the anteriorcerebral or posterior cerebral circulation from the Circle of Willisis involved. Most commonly described in the neuropsychological literature have been ruptured aneurysms from the anterior com-municating arteries, because these affect ventro-medial frontal structures and the basal forebrain. Gade
(37) has argued that it is 
whether or not the septal nuclei of the basal forebrain are impli-cated in the ischaemia which determines whether a persistent amnesic syndrome occurs in such patients. Others have attributed the ﬂ  orid confabulation, which these patients often exhibit, to 
concomitant orbito-frontal damage.
(38)
As discussed above, severe head injury can produce a persistent 
amnesia which may or may not be associated with generalized

(38)
cognitive impairment. There may be direct trauma to the frontal and anterior temporal lobes, resulting in contusion and haemor-rhaging, contrecoup damage, intracranial haemorrhage, andaxonal tearing and gliosis following acceleration-decelerationor rotational forces. Memory function is commonly the lastcognitive function to improve following an acute trauma, and patients can show the characteristic features of an amnesic syn-drome. The phenomenon of ‘isolated retrograde amnesia’ hasbeen described: in such cases, it seems likely that a mild headinjury has precipitated a more purely psychiatric phenomenon. Traumatic head injury is considered in more detail in Chapter 4.1.10 and by Fleminger.
(11)Other causes of an amnesic syndrome

Deep midline cerebral tumours can give rise to an amnesic syn-drome, and this may be exacerbated by surgical or irradiation treat-ment for pituitary tumours. Other infections, such as tuberculous meningitis or HIV , may, on occasion, give rise to an amnesic syn-drome. Mild cognitive impairment and the very early stages of Alzheimer dementia may manifest themselves as a focal amnesic syndrome. Surgical treatment to the temporal lobes for epilepsy can result in profound amnesia, if there is bilateral involvement. There is increasing evidence that focal lesions in the frontal lobes can also produce severe memory impairment on aspects of antero-grade and retrograde memory.
(20) This can occur even in the 
absence of basal forebrain involvement, but it probably results from particular aspects of memory being implicated, including planning and organization, source and context monitoring, and particular aspects of retrieval processes.
(39)

(39)
Neuropsychological aspects
The terms ‘short-term’ and ‘long-term’ memory should be abol-ished from psychiatric discourse, as they cause confusion across disciplines. It is more useful to consider current or recent memory versus remote (or autobiographical) memory. In addition, ‘pro-spective memory’ refers to remembering to do something.
Concepts of memory are considered in Chapter 2.5.3. As des-
cribed in that chapter, a distinction is generally drawn between

cribed in that chapter, a distinction is generally drawn between 
so-called ‘working memory’ , which holds information for brief periods (a matter of several seconds) and allocates resources, and secondary memory, which holds different types of information on a permanent or semi-permanent basis. Secondary memory, in turn, can be subdivided into an episodic (or ‘explicit’) component, semantic memory, and implicit memory. Episodic memory refers to incidents or events from a person’s past, such that he/she can ‘travel back mentally in time’; this is characteristically severely affected in the amnesic syndrome. As mentioned previously, semantic memory refers to knowledge of facts, concepts, and lan-guage. The learning of new semantic memories is variably affected in the amnesic syndrome, although there is now some evidence

that new facts can be learned even in the presence of severe, bilateral medial temporal lobe damage. Other aspects of semantic 
memory, including naming, reading, and comprehension, are affected in disorders where there is concomitant widespread tem-poral lobe pathology, such as herpes encephalitis, Alzheimer dementia, or semantic dementia (a form of frontotemporal demen-tia). Implicit memory refers to procedural or perceptuomotor skills, and to the facilitation of responses in the absence of explicit memory, known as ‘priming’ . Both these aspects are characteristi-cally spared in the amnesic syndrome,
(40) although the precise 
extent of sparing does depend on particular features in the experi-mental design.
(41)
Over the years, there has been extensive debate concerning 
whether the primary deﬁ  cit in the amnesic syndrome lies in the

(41)
whether the primary deﬁ  cit in the amnesic syndrome lies in the 
initial encoding of information, or some kind of physiological ‘consolidation’ into secondary memory, or accelerated forgetting of that information, or in retrieval processes.
(20) There is still very 
little agreement about this debate, but, if anything, the consensus is that retrieval problems are secondary to initial acquisition and consolidation impairments, at least in anterograde amnesia. Retrieval deficits may be more important where there is an4.1.12 amnesic syndromes

SECTION 4  clinical syndromes of adult psychiatry 408
extensive retrograde memory loss,(20) which might account for why 
there is generally a poor correlation between scores on anterograde memory measures and retrograde memory measures.
Much recent research has focused on the speciﬁ  c function of the 
hippocampi, and how there their role is distinct from other struc-tures within the medial temporal lobes, more lateral temporal lobe regions, and the frontal lobes. Suggestions include a particular contribution to the binding of complex associations, relational memory, the binding of the distributed features of an episode into a coherent trace, novel or incremental learning, and a contribution to retrieval processes.
(20,42) Aggleton and Brown(43) have suggested

(20,42) Aggleton and Brown(43) have suggested 
that the hippocampi are critical to the recall of contextual richness and detail, involved in ‘remembering’ or ‘recollection’ , whereas the perirhinal cortex is particularly implicated in the familiarity judge-ments essential in recognition memory. The frontal lobes are generally thought to contribute to planning and organization in memory, aspects of context and source memory, awareness of memory performance (metamemory), prospective memory, and to particular aspects of retrieval processes.
(20,39)
There are also many controversies concerning the nature of the 
extensive retrograde memory loss found in many of the above dis-orders. Modern neuropsychological studies have conﬁ  rmed that

(20,39)
extensive retrograde memory loss found in many of the above dis-orders. Modern neuropsychological studies have conﬁ  rmed that 
this retrograde memory loss can extend back many years or decades, but that it often shows a ‘temporal gradient’ with relative sparing of early memories. The gradient is characteristically steeper in the amnesic syndrome than in dementing disorders such as Alzheimer dementia or Huntington’s disease. Differing patterns of retrograde memory loss can occur; left temporal lobe damage seems to affect memory for facts and for the more linguistic components of remote memory, whereas right temporal lobe damage may affect memory for the incidents in a person’s life.
(20) One theory of retrograde

(20) One theory of retrograde 
amnesia and of the temporal gradient is that, as memories become ‘consolidated’ through time, they become independent of the medial temporal lobes and are relatively protected against brain injury to these structures. A second theory is that, through time, episodic memories adopt a less vivid, more ‘semantic’ form, and this protects earlier memories from the effects of brain injury. A third theory suggests that the hippocampi are always involved in the retrieval and reactivation of memories, and that every time a memory is retrieved, a new trace is laid down, resulting in ‘multiple traces’ protecting against the effects of brain injury.
(44) These three 
theories make differing predictions and, at present, the underlying basis of retrograde amnesia remains hugely controversial.
Confabulation disorders

Confabulation can be subdivided into ‘spontaneous’ confabulation, in which there is a persistent, unprovoked outpouring of erroneous memories, and ‘momentary’ or ‘provoked’ confabulation, in which ﬂ eeting intrusion errors or distortions are seen in response to a 
challenge to memory, such as a memory test.
(20,45)
Confabulation is widely believed to be particularly associated 
with the Korsakoff syndrome, but this is incorrect. Spontaneous confabulation arises in confusional states and in frontal lobe disease.
(45) The link with frontal lobe pathology, particularly in the 
ventro-medial region, has been established in many investiga-tions.
(20,38) Spontaneous confabulation is often seen in the confu-

sional state of a Wernicke encephalopathy, but it is rare in the more chronic phases of the Korsakoff syndrome. On the other hand, ﬂ eeting intrusion errors or distortions (‘momentary confabula-
tion’) do occur in the chronic phase of a Korsakoff syndrome, when memory is challenged. However, such intrusion errors are also seen in healthy subjects when memory is ‘weak’ for any reason, such as a prolonged delay until recall.
(45) They are also seen in Alzheimer 
dementia and other clinical amnesic syndromes, and they are certainly not speciﬁ  c to the Korsakoff syndrome.
There has been considerable interest of late in the nature of 
spontaneous confabulations. Confabulation can extend across epi-sodic, personal semantic, and more general semantic memories.
(46)

(46)
A theory put forward by Korsakoff himself, as well as other author-ities,
(24) emphasizes problems in the temporal ordering of memo-
ries. In a particularly elegant study, Schnider et al.(47) found that a 
group of ‘spontaneous confabulators’ could be differentiated from other amnesic patients and controls on the basis of their errors on a temporal context memory task, but not on other memory or executive tests. More recently Schnider
(48) has interpreted these 
ﬁ ndings in terms of a failure in ‘reality monitoring’ . Somewhat simi-
larly, Johnson et al .(49) has argued that confabulation may reﬂ  ect 
an interaction between a vivid imagination, an inability to retrieve autobiographical memories systematically, and source or context monitoring deﬁ  cits. By contrast, Gilboa et al.

(38) found that a fail-
ure to make fine-grained distinctions within memory could account for Schnider’s observations. They argued that a failure in strategic retrieval and post-retrieval monitoring, related to ventro-medial and orbito-frontal pathology, is critical for spontaneous confabulation to arise. Somewhat similar hypotheses have been put forward by Burgess and Shallice
(50) It has also been argued that the 
content of confabulations may be heavily inﬂ  uenced by motiva-
tional factors.(51)
The notion of ‘confabulation’ or ‘false memory’ has now been

The notion of ‘confabulation’ or ‘false memory’ has now been 
extended to a variety of other disorders, including delusional mem-ory, confabulation in schizophrenia, false confessions, apparently false memories for child sexual abuse, pseudologia fantastica, and dissociative identity disorder. Whilst each of these can potentially be accounted for in terms of a general model of memory and exec-utive function, provided that the social context and some notion of ‘self’ is incorporated, there are likely to be differing mechanisms which give rise to these different types of false memory.
(20)
Neurochemistry and neuropharmacology of 
memory disorders
The Korsakoff syndrome is relatively unusual among memory dis-

(20)
orders in that there is a distinct neurochemical pathology with important implications for treatment. Since animal studies in the 1930s and 1940s, and the important observations of De Wardener and Lennox
(52) and others in malnourished prisoners of war, it has 
been known that thiamine depletion  is the mechanism which gives 
rise to the acute Wernicke episode, followed by a Korsakoff memory impairment. However, the genetic factor that predisposes a minor-ity of heavy drinkers to develop this syndrome before they develop hepatic or gastrointestinal complications of alcohol abuse remains unclear. Transketolase is the enzyme which requires thiamine pyrophosphate (TPP) as a cofactor. Thiamine depletion affects six 
neurotransmitter systems (including acetylcholine, glutamate, aspartate, and GABA), either by reduction of TPP-dependant

neurotransmitter systems (including acetylcholine, glutamate, aspartate, and GABA), either by reduction of TPP-dependant 
enzyme activity or by direct structural damage. Direct genomic PCR sequences of a high-affinity thiamine transporter gene

409
(SLC19A2) have identiﬁ  ed three genetic variants in the Wernicke–
Korsakoff syndrome.(53) Whatever the underlying gen etic mecha-
nism, treatment as soon as possible with high doses of parenterally administered multivitamins is essential in patients with the Wernicke–Korsakoff syndrome. The Wernicke features respond well to high-doses of vitamins, and such treatment can prevent the occurrence of a severe, chronic Korsakoff state.
(20,23) The small risk 
of anaphylaxis is completely outweighed by the high risk of severe brain damage and the appreciable risk of litigation if such treat-ment is not administered.
There has been an extensive literature on the effects of cholinergic 
antagonists  (such as scopolamine) upon memory. Kopelman 
and Corn
(54) found a pattern of impairment in anterograde mem-

and Corn
ory that closely resembled that seen in the amnesic syndrome. It has been argued that cholinergic blockade produces an effect upon the ‘central executive’ component of working memory, but Rusted
(55) has concluded that this is not sufﬁ  cient to account for 
the drug effect upon memory processes. Although some have argued that the predominant effect of scopolamine is on attention, it has been found that covarying for the sedation or psychomotor effects of the drug did not eliminate the strong drug effects on episodic memory tests.
(13,54)  The anticholinesterases, donepezil, 
rivastigmine, and galantamine are now widely used in the manage-ment of Alzheimer dementia.
Despite their very different pharmacological actions, the effects 
of the benzodiazepines  upon memory and attention are remark-

ably similar to those of scopolamine. When recall or recognition is tested after a delay, benzodiazepines produce a marked anterograde impairment in explicit or episodic memory, similar to scopol-amine.
(13) As with scopolamine, however, once learning has been 
accomplished, the rate of forgetting is normal, and benzodiazepines do not produce any retrograde deﬁ  cits.
(13) Procedural learning 
tasks after both benzodiazepine and scopolamine administration show similar effects, with learning curves on the active drug gener-ally paralleling those for placebo.
(13,54) Benzodiazepine effects 
can be attenuated by coadministration of the benzodiazepine antagonist, ﬂ  umazenil.
The effects of catecholamines  upon memory have been studied

The effects of catecholamines  upon memory have been studied 
for many years, but the general consensus is that they act upon ‘tonic attentional processes’ rather than directly upon thestorage or retrieval of memories. In an elegant study, Cahillet al .
(56) examined the effects of the β-adrenergic receptor
antagonist propranolol on memory for an emotionally arousing story, compared with a carefully matched neutral story. Asexpected, subjects given a placebo recalled more of the emotional than the neutral story, when tested 1 week later. Subjects givenpropranolol recalled the neutral story as well as the placebosubjects, but were impaired on the emotional story, whereasstimulation of noradrenaline (with yohimbine) produced some 
enhancement of the emotional elements, and benzodiazepines 
impaired memory equally for both the neutral and emotionalelements of the story.

(13)
Some years ago, there was interest in the serotonergic system
and alcohol-induced memory impairment. Early reports suggested that zimelidine, a serotonin reuptake inhibitor, reversed the memory impairment in healthy volunteers after the administration of ethanol. Later, it was claimed that ﬂ  uvoxamine improved memory 
performance in ﬁ  ve patients with the Korsakoff syndrome, and that 
the improvements correlated signiﬁ  cantly with reductions in a cerebrospinal ﬂ  uid breakdown product. The samples were small, 
and the beneﬁ  ts were minor. Nevertheless, 3,4-methylenedioxy-
methamphetamine (ecstasy) has been reported to produce memory impairments either by direct or indirect effects.
(57) Some of 
the apparent cognitive effects of serotonergic agents may be the by-product of their effects on mood.
(13)

(13)
Of forensic psychiatric importance are agents which produce 
transient but profound amnesia, and may be implicated in offences such as ‘date rape’ . These include ﬂ  unitrazepam (Rohypnol) and 
gammahydroxybutyrate (GHB), and this topic has recently been reviewed by Curran.
(58)
Systematic clinical descriptions of amnesic disorders and their underlying pathology have become more detailed and rigorous over the years. In particular, recent advances in neuro-imaging (structural, metabolic, and activation) have provided theopportunity to relate particular cognitive abnormalities to speciﬁ  c 
changes in brain function. The use of pharmacological agents,in parallel with such imaging techniques, may promote thedevelopment of pharmacological agents more potent than the meagre array that we have at present for the treatment of severe memory disorder.

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PCR sequencing of the high afﬁ  nity thiamine transporter (SLC19A2) 
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4.1.13 The management 
of dementia
The term dementia is used in two different ways. First there are the 
dementias . These are diseases  that cause progressive and diffuse 
cerebral damage, of which Alzheimer’s disease is the most common. Second, dementia can be used to refer to a clinical syndrome . Thus 
dementia is ‘an acquired global impairment of intellect, memory, and personality, but without impairment of consciousness’ .
(1) For 
clinicians this is the preferred usage, and the one adopted in this chapter. It demands that the cause of the dementia is explored, and makes no comment on the likely prognosis.
This chapter will focus on the management of dementia regard-

less of the cause; however given the burden of dementia in older age, the discussion will be invariably, but not exclusively, slanted towards the management of dementia in this age group. Aspects of management speciﬁ  c to individual diseases which produce demen-
tia will be avoided. In addition, a discourse on the management of cognitive and memory problems is excluded as these are described elsewhere (see Chapters 2.5.4 and 6.2.7). Patients who suffer the dementia before 18 years of age will, by and large, not be included; their needs are often best met by services provided for people with 
intellectual disability.
The newly diagnosed patient with dementia
Given that it is now possible to diagnose dementia early in the 
course of the disease it is important to consider when and how to disclose the diagnosis. This is often seen by clinicians as a difﬁ  cult

course of the disease it is important to consider when and how to disclose the diagnosis. This is often seen by clinicians as a difﬁ  cult 
task and one to be avoided until the diagnosis is absolutely certain. Stigma is associated with the diagnosis of dementia; it is perceived as a chronic debilitating illness, with a progressive deterioration in mental faculties that ultimately leads to a loss of self-identity and an unpleasant death. The clinician may believe there is not much to offer until later in disease, and so there is not much point in dis-closing the diagnosis at an early stage. Furthermore, they may ﬁ  nd it difﬁ  cult to break ‘bad news’ , particularly when an individual with 
dementia may not understand or retain information.
Nevertheless, leaving these discussions until the diagnosis is cer-

tain may be too late; the patient’s ability to take part in decisions about their future treatment, and their family’s future, may by then be jeopardized by cognitive decline. Only early in the course of the illness will they be able to make a power of attorney, settle their will, and discuss with their doctors how they wish to be treated once the disease is well advanced.
The way in which the diagnosis is given will affect how patients 
and their families cope and deal with the diagnosis in long-term. Although there are no speciﬁ  c strategies for disclosure of a demen-
tia diagnosis, techniques developed for breaking bad news in dis-closure of cancer diagnosis are probably applicable; for example, the excellent protocol devised by Baile et al.
(2)
Formal psychotherapy and counselling may help patients and

(2)
Formal psychotherapy and counselling may help patients and 
their families come to terms with the diagnosis.(3) Clear simple 
pamphlets or information sheets should be available so that patients and their families can assimilate the diagnosis and its consequences outside of the interview. Referrals can also be made to dementia support groups and local dementia societies; these can provide psy-choeducation, befriending services, and networking groups for patients and their families.
After initial meeting and disclosure, it is important that a follow-
up meeting is arranged; this will allow patients and families to take on board the diagnosis and formulate any questions they might have. Detailed management strategies are probably best discussed during follow-up appointments, as patients and their families might be overwhelmed at the initial appointment.
Genetic counselling and testing for dementia

Many patients and their families are concerned about the herit-ability of the condition and will ask if any genetic tests can be performed. But such a request needs to be considered carefully.
In only about 5–10 per cent of cases is the dementia directly due 
to a high penetrance genetic mutation (for example, early-onset Alzheimer’s, frontotemporal dementia, and dementia associated with Huntington’s disease). Low penetrance gene variants, such as the apolipoprotein E (APOE) genotype, while modulating, for example, the risk of development of Alzheimer’s dementia, do not adequately predict disease development. Consensus groups have therefore advised against using APOE predictive testing.
(4–6)
There are also signiﬁ  cant social ramiﬁ  cations of genetic testing

(4–6)
There are also signiﬁ  cant social ramiﬁ  cations of genetic testing 
for the relatives of patients with dementia; positive tests could have serious implications for employment, family planning, and insurance. Therefore access to appropriate pre-test counselling is important.
Box 4.1.13.1 shows a current modus operandi, based on United 
Kingdom guidelines produced by the National Institute of Clinical Excellence in dealing with this difﬁ  cult subject.
(4) However, the 
clinician is advised to keep abreast of current best practice given the likely rapid advances in this area.
The younger patient with dementia
The incidence of dementia under the age of 65 is rare. However dementia in younger people has signiﬁ  cant additional consequences. 
Often the younger person with dementia has dependents and con-siderable ﬁ  nancial commitments. Spouses may have to give up 4.1.13 the management of dementia

SECTION 4  clinical syndromes of adult psychiatry 412
work to care for their partners and there are very high rates of care-
giver burn-out.
Specialist service provision for the younger patient with dementia 
is often lacking. These patients have different life expectations than their elderly counterparts. Many will be physically ﬁ  t and often do 
not ﬁ  t easily into the service models provided for their elderly 
counterparts. Specialist multidisciplinary teams allied to traditional dementia services have been advocated
(4) although actual imple-
mentation is still required.
Driving
Decisions about whether or not a person with dementia should be allowed to drive are often difﬁ  cult. The patient’s right to autonomy

Driving
Decisions about whether or not a person with dementia should be allowed to drive are often difﬁ  cult. The patient’s right to autonomy 
needs to be balanced against their social and legal responsibilities. The clinician has a duty to consider the safety of other people on the road, as well as the patient themselves. But there is no clear consensus on the best way of making the decision, although a num-ber of regulatory authorities have issued guidance. As a rule of thumb, patients with moderate or severe dementia should not be driving; patients with mild dementia need a careful assessment.
Advice:  Begin with a history from family and relatives; this may

Advice:  Begin with a history from family and relatives; this may 
need to be done while the patient is not present. Have there been any accidents or near accidents? Do they feel the patient is unsafe and shouldn’t be driving? A cognitive assessment (especially of executive and visuospatial function, and psychomotor speed) and physical examination of the patient is of some value although not 
deﬁ nitive. The gold standard is a driving assessment on the road; a 
driving simulator test is an alternative.
Often, as in the United Kingdom, patients are legally obliged to 
inform their driving licensing authority about their diagnosis. The clinician should advise the patient and their relative of this, and 
document the discussion. Difﬁ  culties arise when a patient who is 
not ﬁ  t to drive fails to inform the authority and continues to drive. 
A written warning to stop driving is often sufﬁ  cient, particularly if

A written warning to stop driving is often sufﬁ  cient, particularly if 
the patient and their relatives are reminded that their car insurance policy is no longer valid. In some cases where the patient presents a real risk the clinician may need to break conﬁ  dentiality and inform 
the authorities.
If the patient is deemed ﬁ  t to continue driving, then they should 
be advised about risk reduction, for example keep to well-known routes and avoid busy roads, driving in bad weather conditions, or 
at night. They should be regularly reassessed with regard to their ﬁ tness to drive. Often this has to happen in any case because they 
will only be issued a short-term license (e.g. 1 year).
Behavioural and neuropsychiatric 
symptoms in dementia
Background
Behavioural and Psychological Symptoms in Dementia (BPSDs) 
have been deﬁ  ned by the International Psychogeriatric Association

have been deﬁ  ned by the International Psychogeriatric Association 
(1996) as ‘signs and symptoms of disturbed perception, thought content, mood, or behaviour that frequently occur in patients with dementia’ .
(7)
Identiﬁ  cation, assessment, and management of BPSDs are cen-
tral to good dementia care. These heterogeneous symptoms are highly prevalent in dementia; one study
(8) found that 61 per cent of 
329 patients with dementia exhibited BPSDs, with the most com-mon symptoms being apathy (27 per cent), depression (24 per cent), and agitation/aggression (24 per cent). The presence of BPSDs is cited by carers and relatives as being the most signiﬁ  cant determi-
nant in generating carer stress,
(9) carer burden,(10) and increasing 
the likelihood of subsequent institutionalization.(11)
There appears to be only a weak correlation between the level of

There appears to be only a weak correlation between the level of 
cognitive impairment and the occurrence and severity of BPSDs. Stronger associations have been noted between the presence of BPSDs and the degree of impairment in activities of daily living.
(12)
A complex interplay of factors can give rise to these symptoms 
and include intrinsic host attributes and extrinsic environmental inﬂ uences (Fig. 4.1.13.1). Therefore the same symptom in different

and include intrinsic host attributes and extrinsic environmental inﬂ uences (Fig. 4.1.13.1). Therefore the same symptom in different 
individuals may be due to different causes. For example, aggression may be the response to a delusion in one individual, and the reac-tion to a change in caregiver in another. Often several different problem behaviours are seen in the same patient, such as wandering and sleep disturbance. There may be causal links between different BPSDs, for example the presence of distressing auditory hallucina-tions and persecutory delusions is strongly associated with conse-quent aggression.
(13) Particular constellations of BPSDs are often 
associated with specific dementia syndromes (Table 4.1.13.1). BPSDs will change over time; for example aggression and psychosis 
tend to occur in the early to middle stages of Alzheimer’s dementia whereas incontinence is invariably a feature of late disease.

Of all the symptoms that patients with dementia suffer, it is the 
problems caused by BPSDs that are most likely to trigger a phar-macological intervention or institutionalization. But whether or not a BPSD is reported as being a problem depends heavily on the informant and the situation. For example, night-time wandering may be tolerated by the spouse with the patient in their own home, but not by nursing staff in an acute medical ward.

Assessment of a BPSD begins with a carefully taken informant history to assess the nature, history, and severity of the BPSD, and to garner the background medical, psychiatric, and social history. For example, there may be a history of phobic disorder, which is now manifest as agitation, or a lifelong tendency to aggression. Alcohol or other drug abuse must be addressed. The effect of recently prescribed, and recently stopped, medications needs to be Box 4.1.13.1  Guidelines for genetic testing for dementia
X People likely to have a genetic cause for their dementia (for 
example, familial autosomal dominant Alzheimer’s disease or frontotemporal dementia, cerebral autosomal dominant arte-riopathy with subcortical infarcts and leukoencephalopathy [CADASIL], or Huntington’s disease) and their unaffected relatives should be offered referral for genetic counselling and testing.
X All patients referred for testing should have appropriate

X All patients referred for testing should have appropriate 
counselling in helping deal with psychological and social consequences.
X If a speciﬁ  c genetic cause for dementia is not suspected, as is 
the case in late-onset dementia, genotyping should not be undertaken for clinical purposes.

413
considered. The impact of the BPSD on the patient and the carer 
should be determined. Consider environmental inﬂ  uences; ask 
when the BPSD ﬁ  rst occurred and whether it now occurs at any 
speciﬁ  c time, and whether it is related to any prior activity or 
antecedents. This will aid in formulation of speciﬁ  c behavioural 
management strategies (see below).
The mental state examination will look for evidence of anxiety, 
depression, or psychosis and persecutory delusions, and ascertain the patient’s insight and understanding of their behavioural/neuropsychiatric symptoms. With specific problem behaviours direct observation of the behaviour can be very useful. A thorough physical e xamination will be needed to exclude physical illnesses; if 
suspected then appropriate medical investigations should be consid-ered such as a midstream urine sample or chest X-ray. In agitated 
behaviours, sources of pain and fear should be considered, as well

as the possibility of sleep loss or constipation, cold, or hunger. The presence of any sensory depriv ation (e.g. hear ing loss) s hould be 
looked for. Conversely the patient may be over-stimulated, as com-
monly occurs on general medical or surgical wards because of the 
noise and hustle and bustle.Assessment scales
A range of objective instruments for the measurement of BPSDs 
now exist.(14) Some measure multiple domains, for example the 
Behavioural Pathology in Alzheimer’s Disease rating scale.(15)
Other instruments are speciﬁ  c for one symptom, such as the 
Cohen–Mansfield Agitation Inventory(16) or Cornell scale for 
depression in dementia.(17) There are several caveats to the use of 
such scales, including the large intra-individual variations in scale scores which reﬂ  ects the dynamic nature of BPSDs and variable

such scales, including the large intra-individual variations in scale scores which reﬂ  ects the dynamic nature of BPSDs and variable 
reporting patterns of different observers. Some scales take a long time to complete or require training to administer. Nevertheless in clinical practice, the judicious use of such scales can allow for more reliable assessment of the response to a speciﬁ  c behavioural or 
pharmacological intervention.
Management of agitation and challenging behaviour
Agitation includes behaviour that is aggressive or abusive and occurs at an inappropriate frequency or is socially inappropriate.
(18)
Challenging behaviour has been used as a ‘catch all’ for a number of different behaviours including aggression, combativeness and disruptive vocalizations and may or may not be associated with agitation.
(a) Behavioural interventions
Evidence:  Research into the effectiveness of behavioural techniques

Evidence:  Research into the effectiveness of behavioural techniques 
for agitation and challenging behaviour is based largely on studies using A–B–A–B or single-case design, and case series. Recent sys-tematic reviews suggest that individually tailored behavioural interventions are effective.
(19–22)
Advice:  An intervention programme would start with a situatio nal, 
or ABC, analysis:
X Antecedents—what was happening before the behaviour started?
X Behaviour—a clear description of the behaviour.Fig. 4.1.13.1 Interaction between intrinsic host factors, extrinsic factors, and caregiver factors in the aetiology of BPSDs.BPSDIntrinsic
Factors
E.g.
Physical statusMedicationUnderlying neuropathologyPremorbid personality Extrinsic
Factors
E.g.
Environmental settingLevel of stimulationActivity triggers such asdressing or washing 
Care giver
Factors
E.g.
Interpretation of BPSDCare giver stress vs. coping style

Factors
E.g.
Care giver
Factors
E.g.
Table 4.1.13.1  Common BPSDs in major dementia syndromes
Dementia Common BPSDs
Alzheimer’s dementia Agitation, apathy, depression, anxiety, delusions
Vascular dementia Depression, apathyDementia with Lewy bodies Visual hallucinations, delusions, depressionFrontotemporal dementia Disinhibition, repetitive behaviours, altered 
eating patterns, apathy4.1.13 the management of dementia

SECTION 4  clinical syndromes of adult psychiatry 414
X Consequences—what happened as a result of the behaviour, 
particularly looking for possible reinforcers of the behaviour?
The frequency and severity of the behaviour then need to be 
charted as a baseline before introducing the speciﬁ  c intervention. 
Many programmes rely on the differential reinforcement ofother behaviour ( DRO ); this involves positive reinforcement of 
other, appropriate behaviours, with the hope that these will then replace the challenging behaviour. A useful technique to beused alongside DRO is ‘time out on the spot’ ( TOOTS ), in which 
the unwanted behaviour is met with immediate withdrawal
of social contact; appropriate behaviours receive warm social
contact.
Unfortunately the limiting factor in use of behavioural inter-

contact.
ventions in dementia is the lack of trained individuals; often behav-ioural programmes can only be implemented in specialist units. In addition, the whole nursing/multidisciplinary team must be aware of the principles of reinforcement and extinction of behav-iour, because behavioural programmes are unlikely to be effective unless consistently applied across the team. Evidence for the effec-tiveness of educating carers/family members in behaviour manage-ment techniques is currently inconclusive.
(22) An alternative view

(22) An alternative view 
which is gaining prominence is that while some challengingbehaviours may not be amenable to interventions, it is possible to change the caregiver perception of the problem; this can lead to a reduction in caregiver distress and often by improving an aberrant interaction between caregiver and patient, there is a reduction in the challenging behaviour itself.(b) Psychosocial and environmental interventions
Evidence:  Despite numerous studies there is still a paucity of high 
quality evidence for the effectiveness of psychosocial and environ-mental interventions.
(19,20,22) Some interventions have shown some 
promise helping ameliorate aggressive or disruptive behaviours in dementia. A non-exhaustive selection of the major psychosocial interventions that have been used is shown in Table 4.1.13.2.
Advice:  The interventions should be tailored to the individual

Advice:  The interventions should be tailored to the individual 
person taking account of their level of function and response to the approach. Psychosocial interventions are best applied when there is no clear cause for the disruptive behaviour; they should be only considered when a thorough assessment of the behaviour has be carried out to exclude treatable causes, for example, pain or psy-chosis. Even though certain psychosocial approaches may only have modest efﬁ  cacy in decreasing disruptive behaviour, they may still 
be useful care adjuncts in improving general patient well-being.
(c) Antipsychotics
Evidence:  Short-term treatment with atypical antipsychotics is of 
beneﬁ  t in treating aggression, agitation, and psychosis, although 
the effect size is modest.(4,23,24) With regard to typical antipsychot-
ics, meta-analyses have suggested that haloperidol might improve symptoms of aggression.
(25,26) There is no evidence for beneﬁ  t of

(25,26) There is no evidence for beneﬁ  t of 
longer term treatment (i.e. greater than 3 months).
Adverse effects of antipsychotics may be troublesome, particu-
larly in the elderly; indeed outcomes from the Clinical Antipsychotic Trials of Intervention Effectiveness for Alzheimer’s disease suggested that the adverse effects of atypical antipsychotics offset treatment 
Table 4.1.13.2  Psychosocial interventions in dementia
Intervention Description Evidence for effectiveness
Psychoeducation to staff Educating staff about dementia, neuropsychiatric symptoms, and reduced use of 
restraintPossibly effective—might have sustained beneﬁ  ts
Reminiscence therapy Uses materials related to patient and their era for example, old photographs and 
news articles, to stimulate memories and allow sharing of experiencesPossibly effective

Cognitive stimulation Similar to reality orientation therapy, based on information processing rather than 
orientation knowledgePossibly effective—might have sustained beneﬁ  ts
Music therapy Can consistent of playing music as part of activity sessions or at speciﬁ  c times of 
the day. Music often of patient’s eraPossibly effective—but no evidence of prolonged 
beneﬁ  t
Snoezelen/multi-sensory 
therapyCombined relaxation and use of sensory stimuli e.g. sounds, lights, touch Possibly effective—but beneﬁ  t wears off quickly. 
Also time/staff intensive
Aromatherapy Mostly using lemon balm oil and lavender oil either inhaled or applied 
by massagePossibly effective for agitation and restlessness

Bright light therapy Sustained exposure to high levels of light (up to 10 000 lux) Possibly effective (may be more beneﬁ  t in sle ep 
disturbance than behavioral disturbance). Time/
staff intensive
Pet therapy Contact with animals InconclusiveExercise Walking or light exercise sessions InconclusiveSimulated presence Audiotape recorded by caregiver/family member played to patient where positive 
autobiographical memories are reiteratedNot effective
Reality orientation Regular provision of orientating information e.g. time, date, etc. Not effective
Validation therapy Rogerian-based therapy; allowing resolution of unﬁ  nished conﬂ  icts, the 
acceptance of the reality and the expression of feelingsNot effective

415
advantages in patients with Alzheimer’s disease.(24) Antipsychotic 
use is also an independent risk factor for falls in people with dementia.
(27) Confusion may deteriorate, particularly with drugs 
with anticholinergic effects, and sedation may be problematic. In 
addition, the risk of emergent extra-pyramidal symptoms appears to be signiﬁ  cantly increased with the use of haloperidol and ris-
peridone;
(28) these side-effects manifest even at low doses (for 
example, 1–2 mg of risperidone). Neuroleptic sensitivity is particu-larly evident in dementia with Lewy bodies; severe neuroleptic reactions can occur in up to 50 per cent of these patients.
(29)
There is some evidence for an increased mortality risk for 
olanzapine and risperidone. There may be an increased risk of cerebrovascular adverse events in people with dementia taking these medications.
(30) It is unclear whether this is drug speciﬁ  c or

(30) It is unclear whether this is drug speciﬁ  c or 
a class effect. Meta-analyses have indicated that there is a 1.5- to 1.7-fold increase in mortality risk for people with Alzheimer’s dis-ease treated with atypical neuroleptics. In 2005, the FDA asked the manufacturers of olanzapine, risperidone, aripiprazole, quetiapine, clozapine, and ziprasidone to include warning labels indicating increased risk of death on their products.
(31) In the United Kingdom, 
the Committee for the Safety of Medicines (2004) advised that risperidone and olanzapine should not be used for the treatment of behavioural symptoms of dementia.
(30) More recently, Wang et al.

(2005), reported increased mortality rates in patients over the age of 65 treated with typical neuroleptics compared with atypicals;the risk was greatest shortly after initiation of the treatment and when higher doses were used.
(32) Neuroleptic use has also been 
suggested to hasten cognitive decline although a more recent study refutes this.
(33)
Advice:  A high level of caution needs to applied to the use of 
antipsychotics in dementia. A careful weighing of beneﬁ  ts versus 
the risks is required. General principles for the use of antipsychotics (and other psychotropics) in dementia are similar to psychotropic prescribing for people with head injury (Box 4.1.10.3 in Chapter 4.1.10). Additionally, in dementia:
X Use drugs only if psychosocial or behavioural strategies have

X Use drugs only if psychosocial or behavioural strategies have 
failed, and only if absolutely necessary.
X Review prescriptions regularly looking for side-effects. Patients with 
dementia often have physical co-morbidities and as a consequence take multiple medications; do not allow cocktails to build up.
X Do not prescribe for prolonged periods. Regularly reassess the 
need for the drug; can alternative interventions be applied now the situation is containable?
X For mild to moderate behavioural disturbances, consider the use 
of cholinesterase inhibitors or memantine (see below).
(d) Benzodiazepines

Benzodiazepines can be effective in agitation, particularly if it is associated with anxiety, sleep disturbance, or restlessness. However side effects are frequently associated with benzodiazepine use in people with dementia including sedation, worsening of cognitive function, paradoxical increased agitation, and increased risk of falls. The use of benzodiazepines should therefore be judicious and on a needs only basis. Short-acting benzodiazepines, for example oxazepam or lorazepam, are recommended by some, particularly in the elderly, because they are less likely to result in steadily accu-mulating blood levels.(e) Mood stabilizers
There is limited evidence that carbamazepine may be beneﬁ  cial in

There is limited evidence that carbamazepine may be beneﬁ  cial in 
the treatment of agitation, although there are concerns about its safety in elderly patients given its propensity to induce haemato-logical abnormalities.
(23) High dose valproate does appear to reduce 
agitation, but, again, there is a significant risk of serious side effects.
(34)
(f) Cholinesterase inhibitors and memantine
Evidence:  In addition to providing beneﬁ  ts for cognition in 
dementia (see Chapter 6.2.7), cholinesterase inhibitors mayhelp reduce BPSDs in people with dementia (see Ballard and Howard, 2006, for discussion).
(28) However in most studies 
behaviour improvements have been secondary outcomes anda recent multi-centre 12-week trial of donepezil in patientswith Alzheimer’s disease found that donepezil was no moreeffective than placebo in treating agitation.
(35)One group who do 
appear to gain clear beneﬁ  t from cholinesterase inhibitor use

is people with Lewy body dementia. Rivastigmine at a dose ofup to 12 mg/day for 20 weeks appeared to signiﬁ  cantly reduce
psychotic symptoms in this group.
(36) There is conflicting
evidence for the use of memantine for the treatment ofbehavioural symptoms.
Advice:  In terms of prescribing, it is probably worth considering 
the use of cholinesterase inhibitors and memantine in BPSDs, given their low propensity for serious adverse side effects.
(g) Other agents
Trazodone, a sedative medication, in preliminary ﬁ  ndings appeared 
to be helpful in the treatment of behavioural disturbances. However more recent randomized control trials (RCTs) have refuted the beneﬁ  ts of this medication in dementia.
(28)
Citalopram, aside from its antidepressant properties may have 
some beneficial effects on irritability and restlessness.(37)

(28)
Propranolol has been considered; however, most trials for its effec-tiveness are from old, open label trials. If used, blood pressure and the ECG need to be closely monitored.
(h) Wandering
Many people with dementia will wander, and others will abscond or demand to leave. A risk assessment may be needed to determine their safety outside, for example assessing road safety and their ability to ﬁ  nd their way back home.
Evidence:  The use of two-dimensional grid patterns by the door 
of the ward, environmental sign-posting, or concealing the exit by use of a mirror may possibly reduce inappropriate exiting behav-iour; however the evidence for these strategies is relatively weak.
(22)
There is probably better evidence for behavioural interventions (see above).
(21)
Advice:  Number entry locks which the patient with dementia

(22)
(21)
Advice:  Number entry locks which the patient with dementia 
cannot use can be helpful although it may frustrate the patient. The use of identiﬁ  cation bracelets or tagging systems which sound 
an alarm if the patient leaves the unit is controversial and the sub-ject of ethical debate. An inpatient or residential unit will need both an ‘absent without leave’ policy, which will include the proto-col for informing family and police, and a locked door policy which must take into account what happens if there is a ﬁ  re. 
Detention under a mental health or mental capacity act may need to be considered.4.1.13 the management of dementia

SECTION 4  clinical syndromes of adult psychiatry 416
Mood disturbance
(a) Depression and apathy
Depression in people with dementia is quite common. Therefore it 
is important to consider depression as a cause for almost any change in function or behaviour, and to look for risk factors for depression, for example a recent bereavement, in the history. A screening test to detect depression may be appropriate (see above). Apathy, another common symptom in dementia, may be both a symptom of depression and a consequence of organic brain disease affecting those brain systems involved in motivation.
If the patient is depressed then review the general medical state, 
including any drugs that may produce depression. Make sure that 
all general psychosocial issues have been addressed, for example appropriate support services, leisure activities, and housing. Speciﬁ  c psychological therapy, for instance cognitive therapy, for

all general psychosocial issues have been addressed, for example appropriate support services, leisure activities, and housing. Speciﬁ  c psychological therapy, for instance cognitive therapy, for 
depression in people with dementia is generally unavailable. However there is some limited evidence that a cognitive behav-ioural approach may help in treating depressive symptoms in people with dementia and be of beneﬁ  t to carers.
(38)
(i) Evidence for pharmacological treatment
There is some suggestion that antidepressant treatment of depres-
sion in patients with dementia is effective, although the evidence is limited.
(39) The treatment of apathy in the absence of depression is 
less clear. The is some evidence that cholinesterase inhibitors improve apathy
(40) and case series suggest that bromocriptine and 
methylphenidate are effective, though clinical experience indicates that the effects may be short-lived.
(ii) Advice on pharmacological treatment

The choice of which antidepressant drug to use will depend heav-ily on their side-effect proﬁ  le. Newer antidepressants such as the 
serotonin reuptake inhibitors, having less anticholinergic activity and less cardiotoxicity, are generally preferred. Some method to evaluate the effectiveness of the treatment needs to be in place, preferably before treatment is started to get a baseline measure. For example, a measure of activities of daily living may be thetarget outcome to see whether it improves with antidepressant treatment.
Mania
Mania is rare in dementia, though there is possibly a speciﬁ  c asso-
ciation with Huntington’s chorea. There is no evidence to suggest that mania treatment in a person with dementia be any different from normal protocols.
Psychotic symptoms

The phenomenology of psychotic symptoms inﬂ  uences treatment 
choice. For example, the occurrence of auditory hallucinations with secondary persecutory delusions may be more responsive to antipsychotic therapy whereas delusions of theft, founded on memory impairment, may respond better to psychosocial inter-ventions such as strategies to help the person keep tags on where they put things.
Evidence:  There are few hard data on which to base decisions 
about pharmacological treatment for relieving psychotic symptoms in dementia although there is reasonable evidence that cholinester-ase inhibitors are successful in treating visual hallucinations in dementia with Lewy bodies.
(36)Advice:  The choice of which antipsychotic to use is likely to be 
determined by its proﬁ  le of side-effects. The same cautions and

determined by its proﬁ  le of side-effects. The same cautions and 
advice given for antipsychotic use in agitation in dementia (above) need to be applied for their use in treating psychotic symptoms.
Disorders of sexual behaviour
(a) Impotence or reduced libido
Reduced sexual activity and interest is the most common disorder of sexual behaviour associated with dementia, though it is the least likely to come to the attention of the clinician. It probably plays a part in the high rates of divorce seen, for example, in young couples after one partner has sustained a brain injury. Psychological effects, in particular the change in the patient’s role in the partnership as a result of dementia, as well as the physiological effects of brain dysfunction on erectile function, contribute to impotence and reduced libido.
The ﬁ  rst and most important step is to recognize the problem

The ﬁ  rst and most important step is to recognize the problem 
and talk about it. The couple may wish to be referred to a sexual disorders clinic. If reduced libido is part of a more generalized apathy or depression then it may respond when these features are appropriately treated (see above). Erectile dysfunction may respond to oral phosphodiesterase inhibitors such sildenaﬁ  l.
(b) Sexual disinhibition and overactivity
Any display of sexual disinhibition, although uncommon in 
dementia, is likely to become a major management issue and needs a thorough behaviour assessment. Occasionally it may be part of a Klüver–Bucy-like syndrome with hyperorality and excessive eating.
Sexual disinhibition may respond to behavioural/psychosocial

Sexual disinhibition may respond to behavioural/psychosocial 
strategies. It may, for example, be necessary to ensure that only men nurse the patient if all the sexual disinhibition is directed towards female staff. A full behavioural programme to try to extinguish the behaviour may be effective, but if the behaviour involves touching and groping then it is essential to discuss and monitor the pro-gramme with those involved in the hands-on care of the patient. Staff often ﬁ  nd such behaviour particularly upsetting.
Antipsychotics may reduce sexually disinhibited behaviour. The 
antiandrogens, cyproterone acetate, and medroxyprogesterone 
(Depo-Provera), may need to be tried if all else fails.
Sleep disturbance
Patients with dementia often have a disturbed sleep pattern and this is most troublesome when the sleep–wake cycle is inverted, with the patient asleep during the day but awake at night.
(a) Assessment

It is worth considering restless legs or rapid eye movement (REM-sleep) behaviour disorder as a cause of sleep disturbance. REM-sleep behaviour disorder, often a feature of dementia with Lewy bodies can be successfully treated with low dose clonazepam. Does the patient have to get up at night to empty his or her bladder because of prostatism or bladder dysfunction? Are there othermedical reasons why the patient may be waking at night, for exam-ple because of pain from a duodenal ulcer? Sleep apnoea, more common in the elderly, produces sleep disturbance and is a contra-indication for benzodiazepines and other drugs that may suppress respiration. Is the sleep disturbance due to depression? Has there

417
been any recent change to the sleeping arrangements? If so any 
sleep disturbance may be self-limiting.
(b) Management
Hypnotics are likely to have deleterious effects on cognition and functional abilities, and increase the risk of falls; these drugs should only be considered after techniques to improve sleep hygiene have been tried.
If sleep hygiene techniques fail, there is little deﬁ  nitive evidence 
to guide the clinician as to which hypnotic to select in patients with dementia. Benzodiazepines should, if possible, not be givenindeﬁ  nitely; particular caution is needed if the patient already 
shows disinhibition. Trazodone has been tried, particularly ifthere is co-morbid depression, although the evidence for itsefﬁ cacy is questionable (see above). It has been suggested that 
bright light therapy (Table 4.1.13.2) can resynchronize aberrant circadian rhythms, but there is no deﬁ  nite evidence that it is
effective.
Incontinence

Dementia in the elderly roughly doubles the risk of urinaryincontinence. T o minimize incontinence, toilets should be easily identiﬁ  able and readily accessible. Clothing may need attention
to ensure that it is easy to remove. For urinary incontinencereversible causes, such as urinary tract infection, constipation,and medication (such as diuretics or drugs with anticholinergic side-effects causing urinary retention and overﬂ  ow) should be 
excluded.
A diary recording frequency of voiding on the toilet and fre-

excluded.
quency of incontinence should be kept to see if toileting times can be adjusted to minimize incontinence. Prompted voiding (asking the person hourly if they want to go to the toilet and giving praise for successful toileting) is effective for some individuals. A behav-ioural programme may be needed for the patient who urinates or 
defecates in inappropriate places.
If incontinence persists get the advice of a continence advisor 
before considering drug treatment.
Risk management in dementia
Risk assessment is an important part of the management of patients with dementia and Table 4.1.13.3 suggests various areas of risk that need to be considered. A good history from carers and others involved in the patient’s care is essential for a full risk assessment, which is rarely complete without an assessment by an occupational therapist.
It is important to use the outcome of risk assessment to facilitate

It is important to use the outcome of risk assessment to facilitate 
independence. This is done by introducing appropriate strategies to minimize risk. In addition, a risk–beneﬁ  t analysis may demon-
strate that it is appropriate to run a risk of some adverse event hap-pening if there are clear beneﬁ  ts of doing so. For example, a patient 
may be at risk of wandering and getting lost from his or her home; however, if the strategy to prevent this involves moving the patient to new accommodation away from family and familiar surround-
ings, then this may itself be regarded as a sufﬁ  ciently adverse event 
to make transfer inappropriate. But before implementing such a strategy discuss it with other clinicians involved in the case, and with the carers, family and, if possible, the patient. Document the outcome of these discussions as well as the rationale for the man-
agement plan.Caregivers
The impact and burden of dementia on family and caregivers

The impact and burden of dementia on family and caregivers 
is profound. In addition to the burden of caring, caregivers may experience adverse ﬁ  nancial consequences, loss of independence, 
and social isolation. As a result, caregivers often exhibit high levels of psychological and physical morbidity.
The role of caregivers needs be acknowledged in maintaining 
individuals with dementia in the community. Signiﬁ  cant caregiver 
burden and stress drastically increases the likelihood of care home admission. Therefore support of the caregiver is intrinsic to good dementia care.
Evidence:  There have been a large number of studies examining 
the effectiveness of interventions to support the caregiver. Even though these various studies rarely used the same outcome meas ures a recent meta-analysis was able to show that caregiver interventions can be beneﬁ  cial in reducing caregiver psychological morbidity and, Table 4.1.13.3  Risk assessment in dementia

SECTION 4  clinical syndromes of adult psychiatry 418
importantly, might also delay nursing home admission.(41) Intensive 
interventions that focus on psychoeducation, stress management, and include the person with dementia, seem particularly effective.
Advice:  Support for the family and carers should consist of 
several components.
(4) Start with education about the cause of

(4) Start with education about the cause of 
the dementia, the possible prognosis, and the symptoms—both current and those that may develop. Family and friends need to understand that cognitive and behavioural symptoms arise from damage to the brain and are part of the illness. Caregivers need advice on the principles of care and skills training, for example ensuring that communication is simple and direct, avoidingchanges to routine, not arguing with the patient, but on the other hand not endorsing false beliefs. They will need guidance on when and how to call on professional advice. Caregivers may also need help in obtaining social services input, additional care at home (including cleaning, nursing, and meals-on-wheels), as well as legal and ﬁ  nancial advice. Voluntary organizations such as Alzheimer’s

Society UK (http://www.alzheimers.org.uk) and local self-help groups are often excellent sources of information and support for caregivers.
The burden of caring for someone with a dementia may result in 
depression and other signs of stress. The carer should have the opportunity of talking about any problems they have, if necessary getting their own psychiatric care.
Caregivers who are under stress are probably more likely to 
abuse, either physically or emotionally, the person with dementia. Try to ensure that any physical and emotional abuse of the demented person is picked up early. It helps if everybody involved in the person’s care knows how to report any concerns they may have about what is happening.
Management of end-stage dementia

Previously, little attention was given to the end stages of the neuro-degenerative dementias; most patients would die in hospital or long-term care facilities. However palliative care strategies are increasingly being used in dementia care. These emphasize physical, psychological, social, and spiritual aspects of care, with non-curative interventions aimed at maximizing quality of life. An important principle of treatment in palliative care is propor-tionality; any treatment should only be implemented if the balance of clinical beneﬁ  t outweighs the burden such a treatment imposes.
For patients with dementia good palliative care includes man-
agement of BPSDs. In addition there are a number of end of life issues relevant to dementia:
Swallowing difﬁ  culties and aspiration pneumonia:  These are 
common in end-stage dementia. Ethical consensus has indicated that the use of nasogastric and percutaneous endoscopic gastros-

tomy (PEG) tubes is seldom warranted in end-stage dementia 
although there may be individual cases in which the use of feeding tubes is not futile.
(42) The use of antibiotics is more controversial. 
Certainly in other branches of palliative care there is evidence that even in the terminal stages of illness, antibiotics can relieve the distress caused by infected bronchial secretions.
Pain:  Patients with dementia are often unable to communicate 
their distress. Be alert to the possibilities of pain; indeed always consider if a behavioural symptom is manifestation of pain. The management of pain in dementia is similar to pain management in other conditions. The aetiology of the pain should direct the choice of treatment. Adequate doses of analgesics to achieve good pain

relief should be prescribed.
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4.1.14 Remediation of 
Memory problems are a feature of the majority of psychiatric and

Memory problems are a feature of the majority of psychiatric and 
neurological conditions. Any condition that affects the physical or functional integrity of the brain is likely to have an impact on some aspect of a person’s ability to remember, as successful remember-ing involves many different interacting cognitive systems (seeChapter 2.5.3 on the neuropsychology of memory and Chapter 4.1.12 on the amnesic syndromes). Furthermore, mood disorders such as anxiety or depression, which impair concentration, also reduce the efﬁ  ciency of memory.
Remembering difficulties disrupt the ability to participate 
effectively in activities of daily living, as well as social, leisure,and vocational activities. For some, memory problems will bemild and cause only minor inconvenience in everyday life. Others, such as those with the amnesic syndrome that accompanies dys-

function in limbic system structures, may be severely disabled by 
their memory impairment. People forget to do things (e.g. take medication, turn-off the cooker, pay bills, attend appointments, pass on messages), forget what they have been told, forget people’s names, forget where they left things (e.g. keys, the car in the car park), ﬁ  nd it difﬁ  cult to remember routes or learn new procedures, 
have difﬁ  culty recollecting personal experiences, and so on. Such 
problems lead to frustration, lowered self-confidence, anddependence on others. As such they represent an importanttherapeutic target.4.1.14 remediation of memory disorders

SECTION 4  clinical syndromes of adult psychiatry 420
Assessment of the nature of the memory disorder and the func-
tional consequences for the individual should precede remediation intervention planning. As far as remediation of memory is con-cerned, although the future in terms of biological treatments is promising,
(1) for the present time pharmacological options remain 
limited (see Chapter 6.2.7). The most effective treatments are cog-nitive rehabilitation techniques. These include use of memory aids, which function as cognitive prostheses, and methods of learning that promote more effective acquisition of knowledge or skills.
Planning memory remediation—assessment
The World Health Organization International Classiﬁ  cation of 
Functioning, Disability and Health(2) provides a helpful framework 
for the assessment and remediation of cognitive deﬁ  cits including 
memory impairment.(3) ICF, which complements the diagnostic

memory impairment.(3) ICF, which complements the diagnostic 
approach of ICD, emphasiz es that health (or il lness) and functioning 
can be considered at the level of body structure (pathology), body function (impairment), activities, and participation. Application of this framework in relation to assessment of memory is illustrated in Box 4.1.14.1.
An assessment of memory should therefore address both the 
impairment and the functional consequences for the individual 
patient. This is important because treatment interventions will dif-fer depending on the form and severity of the memory impairment and the nature of the everyday problems. Such an assessment will of course typically be just one part of a broader assessment of 
cognition—memory impairment is the focus here, but the same principles apply to all other cognitive impairments.

Assessment of memory impairment
Memory impairment is assessed through the use of standardized neuropsychological assessment tools (see Chapter 1.8.3).
Assessment of functional consequences of memory 
impairment
Activity limitations arising from memory disorders can be assessed 
through clinical interview with the patient and proxy, but it can also be helpful to use a standardized questionnaire to aid informa-tion gathering. Several questionnaires exist for this purpose. The Prospective and Retrospective Memory Questionnaire
(4) is one

(4) is one 
example of a useful, brief questionnaire with self-rating and proxy-rating forms that address both prospective remembering (e.g. Do you fail to do something you were supposed to do a few minutes later even though it’s there in front of you, like take a pill or turn off the kettle?) and retrospective remembering (e.g. Do you fail to recall things that have happened to you in the last few days?). This questionnaire also has normative data for self-rating and proxy-ratings.
(5,6)
Awareness of the functional consequences of memory impair-
ment may be limited on the part of the patient and the carer(see section on assessment of awareness below). It is possible that functional consequences will also be minimized (again by patient and under some circumstances the carer). In some cases there may be signiﬁ  cant impairment of memory and associated limitations of

activity, but a spouse/family may take on most or all of the remem-bering responsibility and hence the signiﬁ  cant disability on the 
part of the patient may not represent a problem for patient or spouse/family. In this circumstance it is important to investigate whether there is adequate awareness of rehabilitation options.
Assessment of use of memory aids and strategies

Pre-morbid and current use of memory aids and strategies should also be discussed as part of the clinical interview. Given that the most effective approaches to memory rehabilitation are those that enable people with memory dysfunction to compensate for their impairment, it is important to understand what past experience of use of memory aids the patient has, and which aids/strategies are used currently. Some people will have made extensive use of mem-ory aids and strategies throughout their life, and continue to do so in response to onset of memory problems. Others may have used aids and strategies in the past, but then do not use them despite the onset of memory problems. Others have little previous experience. Some examples of aids and strategies to investigate, drawn from a survey of use of memory aids by people with memory impairment,
(7)
are shown in Box 4.1.14.2.
Assessment of awareness of memory deﬁ  cits

(7)
Awareness of impairment should also be examined as this will 
impact on the approach to remediation that will follow. T o what extent is the patient aware of his or her memory (and any other cognitive) problems? Insight and awareness is a complex issue. Clare
(8) presents a biopsychosocial model of the construction of 
awareness in Alzheimer’s disease, though the principles of the Box 4.1.14.1  The WHO ICF model and its relationship to 
assessment of memory
ICF classiﬁ  cation Example in relation to 
assessment of memoryApproaches to assessment/
investigation
Body structure 
(Pathology )Loss of cholinergic 
neurones in basal 
forebrain region affecting functioning of medial 
temporal lobe limbic 
system (Alzheimer’s disease)Physical investigations 
(e.g. routine medical and 
brain imaging investigations)
Body function 
(Impairment )Episodic memory deﬁ  cit Standardized 
neuropsychological assessment tools

neuropsychological assessment tools 
(e.g. Wechsler Memory 
Scales III; Rivermead Behavioural Memory Test)
Activities 
(Disability )Failure to remember 
to do important tasks, 
failure to remember 
events that have 
happened, or things previously toldClinical interview with 
patient and signiﬁ  cant 
other, questionnaires, and observation
Participation 
(Handicap )Inability to work; 
increased dependence 
on others; inability to participate in leisure 
activitiesClinical interview; quality of 
life measures

421
model apply to most neurological and indeed many psychiatric 
conditions. Another simple model, but one that is useful in clinical practice, is the hierarchical model of Crosson and colleagues
(9)
which suggests that awareness may be intellectual ,emergent , or 
anticipatory . Intellectual awareness refers to knowing that you have 
an impairment, but not necessarily recognizing the occurrence of problems as they occur. Emergent awareness refers to ‘online’ awareness of problems as they occur, whilst anticipatory awareness refers to using knowledge of deﬁ  cits to anticipate problems and 
taking steps to prevent problems occurring. This tripartite model of awareness can be helpful in formulating a patient’s level of awareness of memory problems. The extent to which the patient’s reporting of problems is discrepant from their relative’s account (in interview or on questionnaires), or from what might be expected on the basis of standardized test results will give some indication of

level of awareness. In addition it is useful to establish the extent to which the patient is aware of the type of memory problems that arise and the extent to which s/he makes attempt to compensate for the problems. Bear in mind that severe memory impairment may itself impact on awareness—patients may have difﬁ  culty remem-
bering that, or what, they forget.
Planning memory remediation—treatment 
approaches
Memory remediation interventions must take account of several 
factors, including the form and severity of memory impairment, the presence/absence of additional cognitive impairment, and awareness of the deﬁ  cit. With regard to form of impairment, the 
major distinction that is drawn is between primary/working memory and secondary/-term memory.
Remediation of primary/working memory
Primary/working memory refers to the process of brieﬂ  y holding

Primary/working memory refers to the process of brieﬂ  y holding 
verbal or visuospatial information in mind, and in the case of working memory, manipulating information in the mental work-space. Primary/working memory processes are reﬂ  ected in tasks 
such as digit span, with backward digit span seen as taxing working memory. Working memory is considered to be crucial for effective mental control and executive functions such as problem solving. There is some evidence, primarily from studies of patients with a diagnosis of schizophrenia that cognitive training (involving exten-sive practice on tasks, sometimes computerized, which make demands on working memory) improves working memoryper formance over and above control conditions.
(10,11)  Intervention

(10,11)  Intervention 
for working memory problems as part of a more comprehensive cognitive remediation programme should therefore be givenserious consideration, at least for patients with schizophrenia.
(12)
Perhaps ironically, given the acknowledgement that cognitive reha-bilitation for schizophrenia has its roots in neurorehabilitation for traumatic brain injury,
(10) there is a much more limited evidence 
base relating to the effectiveness of this type of intervention with other neurological conditions.
(13)
Remediation of secondary/long-term 
memory problems
Secondary or long-term memory refers to the process of encoding, 
storage, and retrieval of memories after a delay, where ‘delay’ means anything from a few minutes to a lifetime. Secondary memory is what is used to recall episodes, to acquire knowledge and toremember to do things. It is secondary memory that is impaired in amnesia. Box 4.1.14.3 provides a decision tree that reﬂ  ects some

of the processes involved in identifying memory remediationinterventions.
(a) Are there contributory factors?
As part of the assessment and formulation of memory disorders and their functional consequences, one must consider whether a range of other factors are contributing to the functional disability. If so, then one should include intervention for these factors in the treatment plan. This includes treatment of mood disorders, sleep disorders, management of fatigue and pain, or adjustment of medication where possible. In some patients, memory problems will be secondary to Box 4.1.14.2  Assessment of pre-morbid and current use of 
memory aids and strategies
Use of memory aids and strategies is a central component of 
memory rehabilitation. Investigation of prior experience, and current use, of aids and strategies is an important part of the assessment process. Below are examples of aids and strategies that are most commonly used by people with memory impair-
ment.

ment.
(3) This list is not exhaustive and it is important to ask 
whether any other aids/strategies are used.
X Wall calendar/chart/memo board
X Notebook
X Lists (e.g. things to do/shopping)
X Checklists (e.g. instructions for how to operate washing 
machine)
X Appointment diary/personal organizer (e.g. Filofax)
X Asking others to remind you to do something or of things that 
have happened
X Mental retracing (e.g. of steps when lost an object)
X Placing objects in unusual places (e.g. by door if need to take it 
when leaving or as reminder to do something)
X Leaving notes in special places
X Dosett box or other pill reminder
X Repetitive practice (learning something new by frequent 
repetition)
X Making associations
X Watch with date/alarm
X Having a daily routine
X Journal (a daily diary record of personal experiences)
X Daily timetable
X Alarm clock/timer
X Mobile phone (e.g. with alarm reminder/GPS navigation 
function)
X Electronic organizer (Personal Digital Assistant—PDA)

function)
X NeuroPage (paging-based reminding system)4.1.14 remediation of memory disorders

SECTION 4  clinical syndromes of adult psychiatry 422
impaired attention and concentration and if this is the case, then 
interventions to address these problems should be considered.
(b) Is the person aware of the problem?
The question of the patient’s awareness of memory problems should be addressed. If there is no awareness then it is important to consider means of improving awareness before pressing on with speciﬁ  c reme-
diation strateg ies. Improving awareness is sometimes straightforward 
and a question of providing basic information and feedback, but often it is more complex. Use of education and self/other monitoring of memory slips in conjunction with feedback can help. This must be done sensitively as minimizing of problems may be a psychological Memory problem evident from
neuropsychological and/or functional assessment
Are factors other than organic memory deficits contributing
to impaired remembering and everyday memory problems?
Ye s No

Ye s No
Does patient have at least some awareness of memory problem?Identify factors and treatment/
management options
e.g. Other cognitive deficits suchas attention or executive
impairment;mood/worry/anxiety; sleep;fatigue; pain; medication
Ye s No
Has awareness improved?
Ye s No
Consider modifications to environmentto reduce memory demands
e.g. establish consistent routines, use
signs and labels, prompting by carer.
Use of errorless learning strategies for
specific functional tasks (e.g. dressing,other activities of daily living or work
tasks) may be useful How severe is memory impairment?Consider whether approaches
to improve awareness likely to
be effective, e.g. education,feedback,  self/other
monitoring of memory slips.Consider Memory-Groupformat Mild Moderate/severe
Consider memory strategytraining e.g.

Consider memory strategytraining e.g. 
External aids (diaries, notebooks,
watches, mobile phones, PDAs)
External self-talk
Internal strategies (visual
imagery, association, number-
word mnemonics, spaced
retrieval)
Consider use of Memory-Group
formatIdentify priority ‘everyday’remembering needs andselect strategy to reflect need
e.g.Training in use of specific
external aids e.g. dosset box,memo board, diary orchecklists for specific tasks
Externally directed assistive
devices e.g. NeuroPage
Supported learning of
specific information (e.g.errorless learning for learning
names, routes, procedures)
Modifications to environment
Consider use of Memory-
Group format with additional1:1 supportBox 4.1.14.3  Guidelines for genetic testing for dementia

423
coping mechanism and insensitive con frontation may be threatening. 
Working with patients in a group format can contribute to improving awareness—patients can be supported to provide feedback to each other. Patients may feel more able to acknowledge problems if others are also doing this in the group context.
(14)If awareness cannot be 
improved  (which may be the case if memory problems are occurring in 
the context of more global and severe cognitive impairment) then the strategy of modifying the environment to reduce memory demands on the patient must be considered. Environmental modiﬁ  cations include 
the use of pro minent signs/labelling (e.g. of toilets, cupboards, draws, 
rooms) to support orientation in the physical environment. Establishing very ﬁ  xed daily routines can also help develop behav-

ioural habits. It may be the case that the patient requires prompting from carers. If this is the case then the minimal level of prompting required should be established and regularly monitored, and if possible prompting can be gradually reduced as behavioural sequences are learned.
(c) Strategies for mild problems
If the patient demonstrates at least some awareness of memory problems then the severity of the memory problem should be con-sidered. Systematic reviews of cognitive rehabilitation
(15,16)  have 
recommended that different approaches are required for different levels of severity of memory disorder. There is no evidence that ‘drill and repetitive practice’ without additional strategy training is effective in improving memory.
(17,18) However, in the context 
of mild memory impairment then memory strategy training is recommended.

(15) Memory strategy training can be carried out 
on a 1:1 basis or in a group. The aim is to provide informationand training in the use of a range of memory strategies whichthe patient learns to apply independently in speciﬁ  c situations in 
their own life, via homework tasks, over the course of the training programme. The patient is provided with a range of strategy options that s/he can select according to personal needs. This includes training in the use of external memory aids, such as many of those listed in Box 4.1.14.2. Internal memory strategies arealso trained. These include strategies to aid deeper encoding of information. It is a well-established principle that deeper (more meaningful, personally relevant, emotionally salient), multi-modal (i.e. visual and verbal) processing of information results in more effective learning and recollection of that information.

(19) For those 
with severe amnesia whether or not the information is processed deeply will make little difference, but for those with more mild impairment, strategies to enhance processing are more relevant. Strategies include visual imagery, categorization, association with established knowledge, motor movement (e.g. rehearsing in mind an action that has to be carried out at some later time) and spaced retrieval/expanding rehearsal (gradually increasing the time between successive trials of testing recollection of material to be learned). Craik and colleagues
(20) and Evans(1) discuss internal 
strategies further.
(d) Strategies for more severe problems
For those with more severe memory impairment general strategy training is unlikely to be effective as the demands of learning a range of strategies and applying them when required are too great.
(18) The approach recommended in this context is to try to 
map speciﬁ  c everyday remembering priorities to speciﬁ  c strategies.

map speciﬁ  c everyday remembering priorities to speciﬁ  c strategies. 
In other words, rather than providing a tool box of strategies and relying on the patient independently selecting the right tools for

In other words, rather than providing a tool box of strategies and relying on the patient independently selecting the right tools for 
the right task when needed, the clinician establishes with the patient and carer what is essential to be learned/remembered and then considers how can this be achieved. For some this will be just one task for which one remembering strategy will be established. For others a more complex ‘memory system’ can be constructed to allow several remembering tasks to be achieved. Some of the commonly used external aids (memory notebooks, diaries, memo boards) will be used. For people with more severe impairment, formal training in learning how to use these aids consistently is required. A number of studies have shown that comprehensive training approaches can lead to effective use of memory journals, even in people with severe amnesia.
(21–23) Kime(24) provides 
instruction on devising needs-led practical approaches to compen-sating for memory deﬁ  cits.

(e) Electronic memory aids
These aids offer the major advantage of having the facility to 
prompt an action using alarms and so are particularly valuable in relation to prospective memory (remembering to do things). They also provide a means of combining a number of different memory aid functions (e.g. alarmed reminders, schedule, contact informa-tion, to-do list) into one portable tool. The most extensively evaluated electronic reminding system is NeuroPage.
(25) Reminder 
messages are sent to standard alpha-numeric pagers worn by people with memory and/or planning problems, according to a pre-arranged schedule. This system has now been evaluated in randomized clinical trials and single case studies and shown to be very effective.
(25,26) In recent years there has been a massive world-

wide increase in use of mobile phones such that the vast majority of people acquiring cognitive impairment now will have had exposure to this technology before the onset of their memory deﬁ cit. This opens up the possibility of much greater use of porta-
ble reminding technology delivered via mobile phones, including the use of SMS text messaging.
(27,28)
(f) Errorless learning
Another approach to remediation can be applied when there is a need to learn speciﬁ  c information or a procedure. Errorless learn-
ing is based on the principle that for those with severe memory impairment, learning will be most effective if errors can be avoid-ed during the learning process. This is because memory-impaired patients may be more likely to repeat errors (as a result of intact implicit  memory processes), but are unable to recollect that a

response was an error. Thus errors become reinforced. Errorless learning techniques have been used for many years to teach new skills to people with learning disabilities and more recently this technique has been used with people with acquired neurological impairment and with schizophrenia. Baddeley and Wilson
(29)
published the ﬁ  rst study demonstrating that people with amnesia 
learn better when prevented from making mistakes during the learning process. This ﬁ  nding has been replicated with people 
with a diagnosis of schizophrenia.
(30) These were theoretical 
studies of word list learning. However, several single case and group studies have shown the beneﬁ  t of errorless learning meth-
ods in teaching more practical, everyday information including learning names of people important in a person’s life,
(31) work 
tasks.(32) Kessels and de Haan’s(33) meta-analysis concluded that

(31) work 
tasks.(32) Kessels and de Haan’s(33) meta-analysis concluded that 
errorless learning was more effective than standard, ‘trial and error’ conditions.4.1.14 remediation of memory disorders

SECTION 4  clinical syndromes of adult psychiatry 424
Many of the treatment interventions described here are relatively 
labour-intensive requiring a signiﬁ  cant amount of clinician/thera pist 
time for them to be successfully implemented. Occupational Therapists and Clinical Psychologists specializing in neuro-psychology have relevant training in the assessment and treatment of memory disorders and hence memory remediation should be considered within the interdisciplinary context.
Summary and conclusions
Memory disorders are frequently encountered in clinical practice and cause signiﬁ  cant disability. Memory should therefore be 
carefully assessed as part of routine clinical assessment. Restoration of normal functioning is not typically possible and remediation is therefore usually concerned w ith compensating for 
impaired memory. A range of treatment approac hes is available,

impaired memory. A range of treatment approac hes is available, 
and the treatment of choice will depend on the form and severity of memory disorder and the functional problems faced by the patient.
Clare, L. and Wilson, B.A. (1997) Coping with memory problems: a practical 
guide for people with memory impairments, their relatives, friends and carers . Harcourt, London.
Evans, J.J. (2004). Disorders of memory. In Clinical neuropsychology: a 
practical guide to assessment and management  (eds. L.H. Goldstein and 
J. McNeil), pp. 143–63. John Wiley & Sons, Chichester.
Kapur, N., Glisky, E., and Wilson, B.A. (2004). External memory aids and 
computers in memory rehabilitation. In The essential handbook of 
memory disorders for clinicians  (eds. A.D. Baddeley, M. Kopelman, and 
B.A. Wilson). John Wiley & Sons, Chichester.
Information on managing memory impairment is also available in
booklets from Headway, the brain injuries association (www.headway.org.uk/).

 1. Evans, J.J. (2006). Memory dysfunction. In Textbook of neural repair 
and rehabilitation  (eds. M.E. Selzer, M.D. Clarke, L.G. Cohen, P .W. 
Duncan, and F.H. Gage), pp. 461–74. Cambridge University Press, Cambridge.
 2. World Health Organization. (2001). International classiﬁ  cation of 
functioning, disability and health (ICF). WHO, Geneva.
 3. Wade, D. (2003). Applying the WHO ICF framework to the 
rehabilitation of patients with cognitive deﬁ  cits. In The effectiveness 
of rehabilitation for cognitive deﬁ  cits (eds. P . Halligan and D. Wade). 
 4. Smith, G., Della Sala, S., Logie, R.H., et al. (2000). Prospective and 
retrospective memory in normal ageing and dementia: a questionnaire study. Memory ,8, 311–21.

4. Smith, G., Della Sala, S., Logie, R.H., et al. (2000). Prospective and 
 5. Crawford, J.R., Smith, G., Maylor, E.A., et al. (2003). The Prospective 
and Retrospective Memory Questionnaire (PRMQ): normative data 
and latent structure in a large non-clinical sample. Memory ,
11, 261–75.
 6. Crawford, J.R., Henry, J.D., Ward, A.L., et al. (2006). The Prospective 
and Retrospective Memory Questionnaire (PRMQ): latent structure, normative data and discrepancy analyses for proxy-ratings. The British 
Journal of Clinical Psychology ,45, 83–104.
 7. Evans, J.J., Needham, P ., Wilson, B.A., et al. (2003). Which memory 
impaired people make good use of memory aids? Results of a survey of people with acquired brain injury. Journal of the International 
Neuropsychological Society ,9, 925–35. 8. Clare, L. (2004). The construction of awareness in early stage

Neuropsychological Society ,9, 925–35. 8. Clare, L. (2004). The construction of awareness in early stage 
Alzheimer’s disease: a review of concepts and models. The British 
Journal of Clinical Psychology ,43, 155–75.
 9. Crosson, B., Barco, P .P ., Velozo, C.A., et al. (1989). Awareness and 
compensation in post-acute head injury rehabilitation. The Journal of 
Head Trauma Rehabilitation ,4, 46–54.
10. Twamley, E.W., Jeste, D.V ., et al. (2003). A review of cognitive training 
in schizophrenia. Schizophrenia Bulletin ,29, 359–82.
11. Kurtz, M.M., Seltzer, J.C., Shagan, D.S., et al. (2007). Computer-assisted 
cognitive remediation in schizophrenia: what is the active ingredient? 
Schizophrenia Research ,89, 251–60.
12. Wykes, T. and Reeder, C. (2005). Cognitive remediation therapy for 
schizophrenia . Routledge, London.
13. Cicerone, K., Levin, H., Malec, J., et al. (2006). Cognitive rehabilitation

13. Cicerone, K., Levin, H., Malec, J., et al. (2006). Cognitive rehabilitation 
interventions for executive function: moving from bench to bedside in patients with traumatic brain injury. Journal of Cognitive Neuroscience ,
18, 1212–22.
14. Evans, J.J. and Wilson, B.A. (1992). A memory group for individuals 
with brain injury. Clinical Rehabilitation ,6, 75–81.
15. Cicerone, K.D., Dahlberg, C., Malec, J., et al. (2005). Evidence-based 
cognitive rehabilitation: updated review of the literature from 1998 through 2002. Archives of Physical Medicine and Rehabilitation ,
86, 1681–92.
16. Cappa, S., Benke, T., Clark, S., et al. (2005). EFNS guidelines on 
cognitive rehabilitation: report of an EFNS task force. European Journal 
of Neurology ,12, 665–80.
17. Cicerone, K.D., Dahlberg, C., Kalmar, K., et al. (2000). Evidence-based

17. Cicerone, K.D., Dahlberg, C., Kalmar, K., et al. (2000). Evidence-based 
cognitive rehabilitation: recommendations for clinical practice.
Archives of Physical Medicine and Rehabilitation ,81,
1596–615.
18. Clare, L., Woods, R.T., Moniz Cook, E.D., et al. (2003). Cognitive 
rehabilitation and cognitive training for early stage Alzheimer’s disease and vascular dementia (Cochrane Review). In The cochrane library , (4). 
John Wiley & Sons, Chichester, UK.
19. Craik, F.I.M. and Lockhart, R.S. (1972). Levels of processing: a 
framework for memory research. Journal of Verbal Learning and Verbal 
Behavior ,11, 671–84.
20. Craik, F.I.M., Winocur, G., Palmer, H., et al. (2007). Cognitive 
rehabilitation in the elderly: effects on memory. Journal of the 
International Neuropsychological Society ,13, 132–42.
21. Sohlberg, M.M. and Mateer, K. (1989). Introduction to cognitive

21. Sohlberg, M.M. and Mateer, K. (1989). Introduction to cognitive 
rehabilitation: theory and practice . The Guilford Press, New Y ork.
22. Donaghy, S. and Williams, W. (1998). A new protocol for training 
severely impaired patients in the usage of memory journals. 
Brain Injury ,12, 1061–77.
23. Kime, S.K., Lamb, D.G., and Wilson, B.A. (1996). Use of a 
comprehensive programme of external cueing to enhanceprocedural memory in a patient with dense amnesia. Brain Injury ,
10, 17–25.
24. Kime, S.K. (2006). Compensating for memory deﬁ  cits using a systematic 
approach . AOTA Press, Bethesda MD. (www.aota.org)
25. Wilson, B.A., Emslie, H., Quirk, K., et al. (2001). Reducing everyday 
memory and planning problems by means of a paging system: a randomised control crossover study. Journal of Neurology, Neurosurgery, 
and Psychiatry ,70, 477–82.

26. Evans, J.J., Emslie, H., and Wilson, B.A. (1998). External cueing systems 
in the rehabilitation of executive impairments of action. Journal of the 
International Neuropsychological Society ,4, 399–408.
27. Pijnenborg, G.H.M., Withaar, F.K., Evans, J.J., et al. (2007). SMS 
text messages as a prosthetic aid in the cognitive rehabilitation of schizophrenia. Rehabilitation Psychology ,52(2), 236–40.
28. Fish, J., Evans, J.J., Nimmo, M., et al. (2007). Rehabilitation of executive 
dysfunction following brain injury: Content-free cueing improves everyday prospective memory performance. Neuropsychologia ,
45
, 1318–30.

425
29. Baddeley, A.D. and Wilson, B.A. (1994). When implicit learning fails: 
amnesia and the problem of error elimination. Neuropsychologia ,
32, 53–68.
30. Pope, J.W. and Kern, R.S. (2006). An ‘errorful’ learning deﬁ  cit in 
schizophrenia? Journal of Clinical and Experimental Neuropsychology ,
28, 101–10.
31. Clare, L., Wilson, B.A., Breen, K., et al. (1999). Errorless learning of 
face-name associations in early Alzheimer’s disease. Neurocase ,5,
37–46.32. Kern, R.S., Green, M.F., Mintz, J., et al. (2003). Does ‘errorless learning’ 
compensate for neurocognitive impairments in the workrehabilitation of persons with schizophrenia? Psychological Medicine ,
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33. Kessels, R.P .C. and DeHaan, E.H.F. (2003). Implicit learning in memory 
rehabilitation: a meta analysis on errorless learning and vanishing cues methods. Journal of Clinical and Experimental Neuropsychology ,
25, 805–14.4.1.14 remediation of memory disorders

4.2
Substance use disorders
4.2.1 Pharmacological 
and psychological aspects of drugs abuse
Drug abuse, misuse, and addiction are major issues in society 
because of their enormous personal, social, and economic costs and their important psychiatric components.
(1) Many drug treat-
ment programmes are run by psychiatrists, and the evidence strongly supports the notion that a signiﬁ  cant proportion of severe 
drug abusers are psychiatrically ill. Moreover, drug misuse appears to be becoming more frequent in patients with other psychiatric disorders, where it can lead to problems in treatment and poorer outcomes. It is therefore essential for all psychiatrists and related health professionals to have a good understanding of the basis of drug misuse.
Why do people take drugs?
A very common misconception is that drug misuse is simply a search for fun . In fact, people take drugs for many reasons other

A very common misconception is that drug misuse is simply a search for fun . In fact, people take drugs for many reasons other 
than to get the buzz or high. Indeed, studies have shown that straightforward pleasure seeking is the primary reason for initia-tion of drug use in fewer than 20 per cent of individuals. Whilst the high or buzz is the most obvious pleasurable effect, many people also describe using drugs to feel comfortably numb, pleasantly drowsy, or full of energy and conﬁ  dence. Many others will be 
chasing the high or buzz that they ﬁ  rst experienced, always seek-
ing the intensity of their ﬁ  rst experience. Still others will be self-
medicating for anxiety, anger, pain, boredom, lack of motivation, Contents
aspects of drugs abuse
 4.2.2 Alcohol use disorders
 4.2.2.1 Aetiology of alcohol problems

 4.2.2.2 Alcohol dependence and alcohol
problems
 4.2.2.3 Alcohol and psychiatric and physical
disorders
 4.2.2.4 Treatment of alcohol dependence
 4.2.2.5 Services for alcohol use disorders
 4.2.2.6 Prevention of alcohol-related problems
Robin Room
 4.2.3 Other substance use disorders
buprenorphine  
amphetamine and cocaine
 4.2.3.3 Disorders relating to use of PCP and
hallucinogens
 4.2.3.4 Misuse of benzodiazepines  
 4.2.3.5 Disorders relating to the use of 
ecstasy and other ‘party drugs’  

4.2.3.4 Misuse of benzodiazepines  
 4.2.3.6 Disorders relating to the use of volatile
substances  
 4.2.3.7 The mental health effects of cannabis use
Wayne Hall 4.2.3.8 Nicotine dependence and treatment
for drug misuse problems

427
lack of self-conﬁ  dence, and many other aversive states including 
drug withdrawal.
The main reason to try to ascertain the reasons for drug use is that 
in many cases identiﬁ  cation of the cause can lead to effective inter-
ventions. For example, many alcoholics  will point to anxiety  as 
their reason for drinking;(2) indeed, social anxiety is one of the most 
common causes of alcoholism in young men.(3) If this can be treated 
(e.g. by selective serotonin reuptake inhibitors) then they are fre-quently able to become abstinent or even drink normally. Social
anxiety  and attention-deﬁ  cit disorder  are common reasons for the 
use of stimulants. Depression , is particularly likely to lead to excess 
alcohol intake, and a vicious cycle can develop because both alcohol and its withdrawal are depressogenic. Alcohol is also one of the most serious risk factors for suicide. There is increasing use of stimulants
and cannabis  by schizophrenic  patients. In part this reﬂ  ects the

and cannabis  by schizophrenic  patients. In part this reﬂ  ects the 
behaviour of their peer group but in part is because they can offset some of the more negative aspects of the illness and medication side effects. As both these types of drugs can worsen psychotic illness, dealing with drug misuse in this group is a priority.
Other factors affecting drug use may be less amenable to psychiat-
ric intervention, such as pressure from peers  or others. For instance, 
female opiate addicts often have a male partner who also uses drugs or even deals drugs. Should she stop use, relapse is almost certain to occur if she continues to live with this partner. Another reason for drug use is to reduce pain  or boredom , the latter being a common

reason given by disadvantaged youth in areas of high unemploy-ment and poor environmental quality such as inner cities or out-of-town housing estates. Other reasons for drug use, especially with the psychedelics, include the search for meaning  or for mystical expe-
riences . Whilst not directly relevant to psychiatry, this use can pre-
cipitate psychotic episodes in susceptible individuals and may trig-ger schizophrenia.
Finally, it is important to remember that the reasons for use of a 
speciﬁ  c drug are not static. An opiate addict may use the same dose 
of heroin  to get going in the morning, to ‘top off’ a pleasant experi-
ence later in the day, to deal with angry feelings when they occur, and to promote sleep at night. Similarly during a drug-using career

different motivations may become dominant. This has been well characterized in opiate users where for many the initial use was for pleasure or escape. Over months, as physical dependence becomes increasingly apparent, use becomes driven by the need to avoid withdrawal and to feel normal at almost any cost.
Drug use and misuse
It is possible to view the issue of drug abuse from different perspec-tives, which range from the molecular and genetic through the pharmacological to the psychological and social. Each view has its merits and is important, but there is little doubt that an integrated view is necessary, because for most drugs and for most societies no one perspective can explain all the known features of drug abuse. However, for the purpose of this chapter we have concentrated on the psychological and pharmacological.
(1,4–6)

(1,4–6)
Problem use, addiction, dependence, and craving
These are some of the most commonly used terms regarding drug misuse but at the same time they are also the most problematic. The use of drugs in any circumstance, therapeutic, or otherwise, can be associated with problems, although the nature and scale of 
this varies (see Table 4.2.1.1). The terms problem use and misuse usually refer to use of drugs (prescription or otherwise) for plea-sure but with disregard for the personal or social dangers. For example, alcohol misuse can lead to irresponsible behaviour whilst intoxicated and, if prolonged, to liver, gastric, and nervous system damage without the individual necessarily being addicted or dependent.
Addiction  is a term that had become so misused in general par-
lance and had acquired such a pejorative edge, that in the past two decades attempts have been made to remove it from the psychiatric lexicon. Unfortunately, the replacement terminology of depen-

dence , or the dependence syndrome, has been similarly devalued 
by popular usage. In fact there exists a spectrum of dependence ranging from physiological supplementation (as with insulin in 
diabetes mellitus) through to life-altering dependence on illicit 
drugs such as heroin (see Table 4.2.1.1). Addiction is still a useful construct if it is reserved for the collection of phenomena that 
occur at the extreme end of the dependence spectrum, and includes 
the concept of social and personal decline associated with drug 
use, as well as craving, tolerance , and withdrawal  symptoms 
(cf. DSM-IV and ICD-10).
Another area of some confusion is the distinction between phys-
ical and psychological dependence . When originally conceived,

ical and psychological dependence . When originally conceived, 
this distinction was helpful in that it emphasized that drug depen-
dence was more than just physical adaptation to drugs as manifest 
by withdrawal symptoms, and that psychological processes, espe-
cially drug liking, were also important. However, drugs without 
obvious physical withdrawal syndromes (e.g. stimulants) also result 
in measurable physiological withdrawal changes in sleep and activ-
ity as well as measurable psychological changes such as those in mood. In addition, new neuroimaging techniques such as PET, 
SPECT, and functional MRI  are beginning to reveal the brain 
circuits underlying the pleasurable effects of drugs, and this has Table 4.2.1 .1 Potential problems with drug use
Type of drug use and associated 
issuesExamples/effects
Therapeutic use

Adverse effects Sedation, poor drivingDrug interactions Increased drug levelsWithdrawal Convulsions, delirium tremensDrug use with pain Difﬁ  culty reducing opiate dose
Misuse/problem use
Illegality Criminal records; social stigmatization
Intoxication Physical/social damageExcessive regular use Physical/social damageInjecting drug use Infections, thromboses, Hepatitis C
Tolerance Dose escalationWithdrawal Physical dependenceUrge to use/cannot abstain Psychological dependenceCraving/drug seeking Drug dominates life
Drug becomes dominant life goal Personal/social decline
Reinstatement on relapse Cycles of dependency4.2.1 pharmacological and psychological aspects of drugs abuse

SECTION 4  clinical syndromes of adult psychiatry 428
resulted in a blurring of the distinction between physical and 
psychological processes. For example, the plate shows a PET scan of heroin addicts in which the brain regions showing increased blood ﬂ  ow activated by craving for heroin are illuminated using the 
radiotracer oxygen-15 (Plate 4.2.1.1). Similar studies have revealed the brain regions involved in the pleasurable effects of opiates and stimulants.
(7) Thus there is a clear convergence in terms of mecha-
nisms, but in terms of treatment regimens the distinction between physical and psychological remains.
Craving  is also a term that is widely used yet ill-deﬁ  ned. Craving

Craving  is also a term that is widely used yet ill-deﬁ  ned. Craving 
is a desire, which most commonly is taken to mean a strong and sometimes irresistible desire to use a drug. The emotional valence of craving is not necessarily pleasurable. Craving can reliably be elicited in situations of negative valence. It is commonly found in withdrawal, when it can lead to relapse. Craving can also be present as an urge or desire to use a drug although the sufferer may be actively denying or resisting its presence. The complex interplay of physical and psychological processes is well exempliﬁ  ed by the 
physical responses that craving can produce. For example when opiate-dependent subjects are shown drug-related paraphernalia 
they may experience emotions that range from pleasurable anti-

cipation to early withdrawal (shaking, tearing of the eyes, pupil dilatation, etc.). Each one of these experiences can lead to a desire to use the drug, that is craving.
Studies in both animals and humans have demonstrated
that conditioning  occurs to both the positive and negative
aspects of craving.
(8)T olerance  is to a large extent a conditioned
response, particularly related to the environmental context in which a drug has been taken.
(9) Thus an environmental context

(9) Thus an environmental context 
which is drug familiar results in physiological changes in thebrain in preparation for the drug effect, and thus less actual drug effect occurs (i.e. tolerance). However, in a novel context, suchpreparatory changes do not occur so that a standard drug dose will result in a larger drug effect and a potentially fatal outcome. Thus the lethality of a drug is largely dependent on the environment in which it is taken.
Attempts have been made to dissect out the subcomponents of 
craving using questionnaires. The best known of these are the set designed by Tiffany et al.
(10) who independently rate the ﬁ  ve main

(10) who independently rate the ﬁ  ve main 
subcomponents of craving—urges and desires to use, intention and planning to use, anticipation of positive outcome, anticipation of relief from withdrawal or negative outcome, and loss of control over use. Ongoing neuroimaging studies are beginning to support this multiprocess view of craving by revealing activation or inhibi-tion of different brain regions to be correlated with individual symptom clusters.
There is also increasing evidence that the particular cognitions
of patients may be important for treatment, especially during withdrawal. Just as panic disorder patients have catastrophic cogni-tions, addicted patients may have a high fear of craving and other withdrawal symptoms in association with related catastrophic cognitions. This detoxiﬁ  cation fear has been measured in opiate

addicts, and shown to predict outcome.
(11) Withdrawal expectations 
also play a signiﬁ  cant role,(12) and a 15 to 30 min explanation of 
what the opiate detoxiﬁ  cation involves may reduce the measured 
withdrawal distress by over one-third. Indeed, such is the strength of psychological factors in addiction treatment, there is little doubt that drug treatments should always be combined with the appro-priate psychological interventions.Psychological processes and 
treatment implications
One of the most inﬂ  uential models in addiction treatment is known 
as the stages of change model .(13) The stage of change that a per-

son can be identified as being at determines the therapeutic approach and type of treatment offered. Thus at the precontempla-tion stage where there is no recognition of a need for treatment, there is no point in offering intensive treatment interventions. Similarly, at the contemplation stage when treatment is being con-sidered, the appropriate intervention is to help the person clarify their views and build their motivation to change rather than offer-ing active treatment. Indeed, it is only in the decision and action stages that treatment should be actively offered and facilitated.
The brief counselling technique of motivational interviewing
(14–16)
has been proved to improve outcome effectively, and ties in well

(14–16)
has been proved to improve outcome effectively, and ties in well 
with the stages of change model. In the early stages the therapy is focused on encouraging the patient to reduce or resolve their ambivalence, which acts as their psychological barrier to treatment. The patient in this client-centred but focused therapy is facilitated to discover the solutions to their own problems themselves. This approach of accepting the client’s current level of thinking (rather than offering ready-made solutions, or confronting them, or trying to argue them into the solution) has been shown to be surprisingly effective in the clinical trials.
(16) The effectiveness of this technique 
has resulted in a new understanding of motivation, which is seen as a dynamic state rather than as a ﬁ  xed state, and one which can be 
inﬂ uenced by the therapeutic stance.
Other cognitive therapies also make signiﬁ  cant contributions to

Other cognitive therapies also make signiﬁ  cant contributions to 
treatment. Relapse prevention  involves the teaching of cognitive and 
behavioural strategies for dealing with high-risk situations and men-tal states.
(17,18) Other cognitive behavioural therapies , including 
extinction of conditioning, contingency management, community reinforcement techniques,
(19) and indeed Beck’s cognitive therapy,(20)
have been effectively applied to substance misuse. The very large Project MATCH (matching alcoholism treatments to client heteroge-neity) study of alcohol treatments compared three types of treatment and found that motivational enhancement, 12-step facilitation, and cognitive behavioural therapy were equally effective overall, although each therapy excelled in certain subgroups.
(21,22)  Based on these results 
it seems likely that speciﬁ  c therapies targeted at speciﬁ  c issues of

it seems likely that speciﬁ  c therapies targeted at speciﬁ  c issues of 
importance in patients with addiction are roughly equally effective overall, but that we do not yet know enough to conﬁ  dently match
speciﬁ  c patient subtypes to speciﬁ  c therapies.
A number of other therapies  have also been shown to be effective, 
particularly in the alcohol ﬁ  eld, including self-control training, 
self-help groups, marital and family therapy, coping and social skills training, anxiety and stress management, aversion therapies, and brief intervention strategies.
(23,24)  The Cochrane reviews found 
that there was insufﬁ  cient evidence to prove the effectiveness of 
psychosocial interventions used alone, but that there was added beneﬁ  t from combining such interventions with pharmacological 
treatments in both maintenance and detoxiﬁ  cation.
(4–6)
Personality variables and the genetics 
of addiction

(4–6)
The role of personality in addiction is a major issue, with some 
believing in an ‘addictive personality’ and others suggesting

429
different personality types might predispose to different aspects or 
forms of drug misuse.(1) In this highly controversial ﬁ  eld a few facts 
are generally agreed. Predisposition to experiment with both licitand illicit drugs is more likely in those with sensation-seeking or impulsive behaviour traits, and in extroverts rather than introverts. However, once drug dependence is established, those with obsess-ional, dependent, or anxious characteristics ﬁ  nd it hardest to stop.
(1)
The genetics of drug abuse are beginning to be unravelled and 
already these studies have thrown up some important insights in relation to personality. The best studied dependence is that on alco-hol, where the Scandinavian adoption studies have found the risk of alcoholism in male children of male alcoholics is the same regardless of whether the child is reared with the alcoholic father or by a non-drinking adoptive family. Building on these data, Cloninger
(25) has

(25) has 
identiﬁ  ed two main forms of alcoholism. Type I is the late-onset 
form that has low inheritance and is associated with anxiety and stress which drinking is used to relieve, often in binges. In contrast, Type II alcoholism starts at a younger age with a heavy regular intake and is associated with antisocial personality traits and criminality. This form is male limited, is associated with impulsivity, and may be related to underfunctioning of brain 5-hydroxytryptamine systems, as genetic polymorphisms of 5-hydroxytryptamine receptors and enzymes have been found in these subjects.
(26)
How abused substances affect the brain
The brain works by transmitting information between neurones using the primary neurotransmitters. The primary neurotrans mittersare glutamate, which is stimulatory (i.e. it turns neurones on), and 
the closely related amino acid γ-aminobutyric acid (GABA), which

the closely related amino acid γ-aminobutyric acid (GABA), which 
is inhibitory (i.e. it turns neurones off). The appropriate balance between these neurotransmitters leads to the brain processes underlying action, sensation, learning, and memory. Secondary 
transmitters  are the monoamines and peptides such as dopamine, 
5-hydroxytryptamine, noradrenaline (norepinephrine), acetylcho-
line, and endogenous opiates. These add the tone, valence, and emotion to the primary processes, and some such as noradrenaline are important in memory formation. All ‘drugs’ (probably even sol-vents through indirect effects) act by interfering with these neu-rotransmitters in ways summarized in Table 4.2.1.2. However, it is important to realize that the brain has its own endogenous ‘addic-
tive’ neurotransmitters . The best known are the endogenous opi-

oid peptides such as the endorphins and enkephalins, but there are also endogenous cannabinoids (anandamide) and probably others. It is not yet known whether these endogenous substances are medi-ators of addiction to cannabis or other drugs, although this would certainly seem possible.
(27–29)
What is certain is that some of the most addictive agents 
(especially the full agonist opiates such as heroin/morphine) act on the endogenous opioid neurotransmitter pathway , but with a 
much greater effect than the natural transmitter. The profound ability of opiates such as heroin to produce addiction is because these drugs highjack the natural transmitter system leaving normal levels of stimulation seeming tame by comparison. Treatment with partial agonist opiates such as buprenorphine  offer a compromise 
in that they are less addicting than heroin yet restore some of the 
Table 4.2.1.2  Drugs and transmitters

Drug class Endogenous transmitter Treatment implications
Mimic natural transmitters
Opiates (alcohol) Endorphins/enkephalins Antagonists (naltrexone)
Partial agonists (buprenorphine)
Cannabis Anandamide/others AntagonistsAlcohol GABA GABA modulator (? acamprosate)Benzodiazepines/barbiturates GABA Partial benzodiazepine agonists
Antagonists (ﬂ  umazenil)
Nicotine Acetylcholine Antagonists (mecamylamine)
Partial agonist (varenicline)
Release transmittersCocaine (buproprion) DA Other uptake site blockersAmphetamines DA D2-receptor antagonists/partial agonists
As cocaine
Nicotine DA As cocaineEcstasy 5-HT/DA 5-HT uptake blockers/antagonistsAlcohol, solvents? NA/DA NA/DA uptake blockersBlock transmittersAlcohol Glutamate Glutamate modulators (acamprosate)Barbiturates Glutamate Glutamate modulatorsLSD/other psychedelics 5-HT Antagonists

DA, dopamine; GABA, γ-aminobutyric acid; 5-HT, 5-hydroxytryptamine; NA, noradrenaline.4.2.1 pharmacological and psychological aspects of drugs abuse

SECTION 4  clinical syndromes of adult psychiatry 430
brain’s deﬁ  ciency of opiate tone. They also have the advantage of 
being much safer than full agonists in overdose and rarely cause death from respiratory depression.
(30) Other drugs, in particular 
alcohol, seem to act in part by indirectly stimulating the endoge-nous opioid system, which is why opioid antagonists such as naltrexone can be useful treatments.
(31)
Other drugs act on the natural stimulant transmitter dopamine .
Dopamine deﬁ  ciency (for instance in Parkinson’s disease) has long 
been known to limit motor behaviour. Stimulant drugs increase energy and stamina by increasing the synaptic levels of dopamine, either by increasing the release or by blocking its reuptake in the basal ganglia. Many drugs of addiction can also increase dopamine availability in other brain regions, the two most important being the nucleus accumbens and the prefrontal cortex.
(32) A huge body

(32) A huge body 
of evidence points to the nucleus accumbens as being a critical gateway in drug misuse. Most abused substances (with possible exceptions of opiates and be nzodiazepines) act to  increase dopamine 
release in this region. How they do this varies—cocaine and nico-tine act at the level of the dopamine terminals, whilst cannabis and alcohol activates the cell bodies in the brain stem. The net effect is to increase dopamine transmission out of the nucleus accumbens into the basal ganglia and thalamus, frontal cortex, amygdala, and hypothalamus.
(1)
This circuit is the one that was shown by Olds in the 1950s to 
sustain electrical self-stimulation in rats and is the brain’s own reward circuit . It is normally activated by positive reinforcers, such

sustain electrical self-stimulation in rats and is the brain’s own reward circuit . It is normally activated by positive reinforcers, such 
as food, water, and sex that are critical to survival. Because drugs of abuse produce greater effects than the natural reinforcers, the resul-tant effect is that the brain directs its normal drives away from the natural reinforcers and towards the more pleasurable drugs. In severe addiction, which frequently occurs with the most powerful reinforcers (such as heroin and cocaine), all natural drives may be subsumed to an overwhelming search for and use of the drug. Thus addicts may give up sex, grooming, hygiene, relationships, work, hardly eat or drink, and ignore health problems.
The routes and risks of addiction
In addition to its impact on the social aspects of life, drug misuse can lead to signiﬁ  cant medical problems. The dangers of drug

In addition to its impact on the social aspects of life, drug misuse can lead to signiﬁ  cant medical problems. The dangers of drug 
abuse relate to two main factors; the route of use of the drug and the effects the drug has outside of the reinforcement circuit of the brain.
For most drugs of abuse the faster the drugs reach their target 
site in the brain the better they are liked and the more psychologi-cally reinforcing they are. Indeed, the ‘pharmaceutical’ history of most abused drugs illustrates the progressive reﬁ  nement of their 
preparation, in order to accelerate their rate of entry into the brain. A good example is cocaine . The Andean Indians originally experi-
enced its effects from chewing coca leaves, which released low levels of cocaine slowly. An increase in vigour and a resistance to fatigue is produced, but little pleasure. Over the centuries cocaine has 
become more reﬁ  ned, ﬁ  rst to paste and then to cocaine hydrochlo-

ride powder (snow) which when taken nasally produces high levels in the brain within 5 to 10 min and a clear ‘high’ . Further reﬁ  ne-
ment to the free base produces a more lipophilic form (crack) that can be smoked, resulting in entry into the brain in seconds. Intravenous drug use also serves the same purpose of getting the drug to the active site very fast.A similar process of pharmaceutical reﬁ  nement to accelerate brain 
entry has taken place with the opiates . Smoking opium is a method 
of delivering morphine and related substances reasonably quickly but in low amounts. Reﬁ  ning opium into its active constituents (e.g.

of delivering morphine and related substances reasonably quickly but in low amounts. Reﬁ  ning opium into its active constituents (e.g. 
morphine) means that higher doses are more easily ingested. However, morphine crosses the blood–brain barrier relatively slowly and has therefore been largely supplanted by opiates such as heroin that cross more rapidly. Heroin is a diacetylated synthetic derivative of morphine that is more lipophilic, meaning that it is able to enter the brain more rapidly and give a better rush. Interestingly, the active form of heroin is morphine; heroin has to be deacetylated beforeit can act, which proves that pharmacokinetic differences are the critical variable with opiate preference. Similarly, codeine is alsoinactive until metabolized to morphine, but because this happens very slowly codeine has less abuse potential than morphine.
The benzodiazepines  were abused relatively rarely until the 
advent of gel-ﬁ  lled capsules of temazepam. These provided experi-

enced intravenous opiate users with a convenient source of a con-centrated drug, which they began to experiment with in the late 1980s. In an attempt to stop this, the drug was reformulated in wax, which led to users heating up the caplets until they melted and then injecting the hot solution into their veins (hot lining). Unfortunately at body temperature the wax solidiﬁ  ed, blocking the veins and 
arteries into which it was administered, leading to severe ischaemia that often lead to gangrene and the loss of the limb. Since there are no therapeutic advantages of temazepam over other benzodiaze-pines that are much less abusable, this drug has recently been put under a higher degree of regulatory control in the United Kingdom in order to deter its prescription and misuse.
As well as affecting the relative reinforcing actions of abused

As well as affecting the relative reinforcing actions of abused 
drugs, the rate of brain entry  also contributes to risk. A very rapid 
drug entry makes dose adjustments difﬁ  cult or impossible and so 
predisposes to overdose. This is most obvious for intravenous use of opiates where respiratory depression is the main cause of death, but is less common with smoked opiates as intake can more easily be titrated to the desired effect.
The route of use  also affects risk, most notably with the risk of 
infection from intravenous use, especially when needles are not cleaned or are shared. The majority of current intravenous users are Hepatitis C positive and we can therefore expect cirrhosis to become a major cause of their death in the next decade or so. This also raises ethical and economic issues; interferon treatment signiﬁ  cantly reduces the progression of the disease but is costly and

its routine use in addicts would be massively expensive and likely to cause public disquiet. The other main infections are hepatitis B and AIDS. The frightening rise of AIDS in drug abusers, where it occurred faster than in any other group, was the main impetus to the harm-reduction approach becoming the treatment style of the 1990s. Needle-exchange programmes and increased methadone 
availability were both proven to reduce the spread of AIDS and 
have become the cornerstone of treatment in many countries.
Relative risks of abused drugs
This is a critical issue in relation to directing legal as well as medical inputs into drug abuse. There are four main factors, which have to be taken into account in determining relative risk:
(33)
X risk due to the route of use
X risk of the drug itself

431
X extent to which the drug controls behaviour (addictiveness)
X ease of stopping
The risks due to the route have been covered above. The risks of 
the drugs themselves are determined by standard tests and clinical 
experience and can be encapsulated in concepts such as the thera-
peutic index . This is the ratio of toxic dose to therapeutic (or usual) 
dose. The ratio is very low for heroin and similar opiates, for cocaine especially crack, and for intravenous temazepam and oral ecstasy. It is quite high for psychedelics, cannabis, benzodiazepines, and orally used stimulants such as amphetamines. Another impor-tant consideration is the health complications  of long-term use, 
which by and large reﬂ  ects the therapeutic index. An exception to

which by and large reﬂ  ects the therapeutic index. An exception to 
this is the opiates, which, provided sterile administration is used, are thought to have little detrimental effect, even when used chron-ically and intravenously. Chronic cocaine can lead to cardiac dam-age, and heavy cannabis smoking causes precancerous change in the same way as tobacco smoking, as well as causing greater levels of chronic bronchitis.
The degree of control over behaviour  that the drug elicits is a 
major factor in drug dependence, and is the closest concept to addictiveness. Although the route of administration is another critical variable, we can make some reasonable generalizations. Strong opiates and cocaine are the most addictive, being overall as addictive as nicotine. The benzodiazepines, ecstasy, and psychedel-ics are the least addictive, and are signiﬁ  cantly less addictive than 
alcohol.
There are three main factors contributing to drugs gaining con-

alcohol.
trol over behaviour, all of which affect the ease with which a drug may be stopped. The ﬁ  rst is the pleasure a drug produces—the pos-
itive drive for use (pleasure giving and seeking). The others both involve the pain of abstinence—withdrawal in both physical and psychological terms—which leads to drug use to relieve it (discom-
fort escape). The pattern of drug use during an addiction career 
generally begins with the quest for pleasure and progressively evolves into the escape from withdrawal pain as neuroadaptive 
processes develop. In this context it may be thought that withdraw-al discomfort is best limited to symptoms with a clear physical symptomatology, that is the autonomic symptoms indicative of physical dependence. But in terms of addictiveness, psychological withdrawal may in fact be more important than physical with-drawal. This is illustrated by the ﬁ  nding that those dependent on

opiates for medical reasons, although physically dependent, experi-ence little craving and risk of relapse once detoxiﬁ  ed, provided the 
reason for being on the opiate resolves. The ease of stopping the drug thus depends on both the physical and psychologicalwithdrawal symptoms, as well as the ability of the drug to provide positive reinforcement.
It is possible to provide rough guides for these three processes
for each drug, so that the overall addictiveness potential can be gauged (Table 4.2.1.3). For completeness, the main licit drugsare also shown as well as another highly motivated behaviourwhich can produce a state of addiction/dependence, that isgambling.
Nutt, D.J., Robbins, T.W., Stimson, G.V ., et al. (2006). Drugs and the future: 
brain science, addiction and society . Elsevier, Burlington, MA.
NIDA (National Institute on Drug Abuse) www.nida.nih.gov
SAMHSA (Substance Abuse and Mental Health Services Administration) 
www.samhsa.gov

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Pleasure giving Physical 
withdrawal 
problemsPsychological 
problems
Opiates +++ +++ +++
Amphetamines ++ + +Crack/cocaine +++ ++ +++Cannabinoids + + +Barbiturates ++ +++ ++Benzodiazepines + ++ ++Ecstasy ++ + 0Psychedelics ++ + 0Cigarettes +++ + +++Alcohol ++ +++ ++Caffeine + + +Gambling ++ 0 ++

0 none; + slight; ++ moderate; +++ strong.4.2.1 pharmacological and psychological aspects of drugs abuse

SECTION 4  clinical syndromes of adult psychiatry 432
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369, 1047–53.4.2.2 Alcohol use disorders
4.2.2.1 Aetiology of alcohol problems
Approximately 8 out of every 10 persons living in Europe and the 
Americas would report consuming alcoholic beverages in their life-time,
(1) and the norm is for drinking to start in adolescence: in 
2003 the average age of ﬁ  rst drink in the United States was 14 years 
old.(2) Also in the year 2003, 79.3 per cent of persons aged 15 years

old.(2) Also in the year 2003, 79.3 per cent of persons aged 15 years 
or more in Canada reported to be current users of alcohol, and 22.6 per cent admitted to having exceeded the country’s safe drink-ing guidelines (i.e. no more than 14 units/week for males and 12 units/week for females). The same survey elicited a rate of ‘haz-ardous drinkers’ of 13.6 per cent, deﬁ  ned as all respondents who 
scored 8+ on the AUDIT screening questionnaire.
(3)
Epidemiological data in the United States indicates that roughly 
one in seven persons who start drinking will develop an alcohol dependence disorder in the course of their lives.
(4) The ﬁ  gure is 
higher among men when compared to women. Of course it is also higher if other clinical forms of alcohol misuse (i.e. alcohol abuse/harmful drinking) are included in the rates in addition to dependence.
A moderate level of alcohol use appears to be relatively harmless;

A moderate level of alcohol use appears to be relatively harmless; 
and there exist public health guidelines on ‘safe’ drinking practices. The recommendations vary considerably from country to country, but they all assume a greater vulnerability to alcohol effects in the female gender. In the United Kingdom, for instance, hazardous drinking is thought to start at 21 units/week for men and 16 units/week for women;
(5) and in the United States the equivalent guide-
lines are 14 and 7 drinks per week.(6) It is among alcohol users who 
exceed such guidelines that the prevalence of dependence is the highest; up to 40 per cent of the more frequent violators.
(7)
The expression ‘alcohol problems’ encompasses a wide range of

(7)
The expression ‘alcohol problems’ encompasses a wide range of 
untoward occurrences, from maladaptive, impaired, or harmful behaviour, to health complications and the condition of alcohol dependence. Alcohol problems are not incurred just by chronic excessive drinkers, but also by persons who drink heavily on isolated occasions (e.g. accidents, violence, poisoning, etc.). Given their Contents
 4.2.2.2 Alcohol dependence and alcohol problems
 4.2.2.3 Alcohol and psychiatric and physical disorders
Robin Room

433
high frequency and social costs, these consequences of acute ine-
briation represent the most signiﬁ  cant public health burden of 
drinking.(8) This section focuses rather on the causes of problems 
of a clinical nature, the ones presented by individuals who engage in patterns of repeated excessive drinking, i.e. ‘alcohol dependence’ and ‘alcohol abuse’ (DSM-IV nomenclature) or ‘harmful drinking’ (ICD-10 nomenclature).
The causality of alcohol misuse
Alcoholism is a bio-psychosocial phenomenon par excellence;it results from the contribution of multiple individual andenvironmental risk factors. The complex dynamics inﬂ  uencing its 
development have been well acknowledged in the literature. Theories have taken many disparate facts into consideration, from the effects of alcohol policy to the inﬂ  uence of familial and socio-

cultural environments across cultures and over time. Some ethnic groups, for instance, have traditionally had low rates of alcoholism (Asians, Jews, and some North American Aboriginals) and the prevalence is generally higher in males across both age cohortsand ethnicities. Another layer of complexity lies in the fact that alcoholism is a clinically heterogeneous disorder with variable age of onset, drinking patterns, severity, and comorbidity with other mental disorders. In general, alcoholics have one or more clinical 
diagnoses in addition to alcohol dependence, including drug

abuse, antisocial personality disorder, anxiety, and depression. The course of the disorder is variable with high rates of remissionand relapse; its manifestation changing in pattern and severityin response to life events (stressors) and other aspects of theenvironment. A summary of the etiological factors that havebeen shown to inﬂ  uence the development of alcoholism is shown 
in Box 4.2.2.1.1.
Sociocultural factors
Macrocultural inﬂ  uences such as values, beliefs, and mores; social 
role functions; local economy; customs and dietary habits; rapid social change; and cultural stress do shape and dictate the wayalcohol is used in human societies. But even within a single society, there is variance in the alcohol problems profile of differentsubgroups. For instance, drinking, heavy drinking, alcohol usedisorders, and treatment for alc oholism are more frequently 
recorded in men than women,

(1) the risk of hospital admission for 
alcoholic psychosis, acute intoxication, and liver cirrhosis iselevated in unskilled and blue-collar workers when compared with higher occupational categories; alcoholics are over-represented in occupations with ﬂ  exible work schedules, in those less supervised, 
and in the ones which facilitate access to alcohol,
(9,10)  and although 
there are a larger proportion of regular alcohol users among the older, the wealthier, and the better educated, frequency of heavy drinking (i.e. episodes of intoxication, 5+ drinks at a time) is inversely correlated with age, income, and level of education.
(3)
Cultural beliefs about drinking and related social norms largely

(3)
Cultural beliefs about drinking and related social norms largely 
determine the manner in which alcohol is used. Disorderly con-duct and drunken violence are more likely to occur in societies which, while allowing drinking, do view alcohol as an evil substance. Similar consequences can be expected if drunkenness is culturally considered as a ‘time out’ , when socially unacceptable behaviours are tolerated or excused.
(11) In fact, the social condoning of
drunkenness is considered as an epidemiological risk factor.The availability of alcohol and the social promotion of frequent or 
heavy drinking are examples of social risk. But environmentalfacilitation per se  does not explain the genesis of an alcohol
dependence disorder in speciﬁ  c individuals. This disorder is best 
understood as the result of social prompting and individualvulnerabilities.
Psychological factors

Alcoholics do not present a homogeneous premorbid personality proﬁ le. However, some distinctive trait clusters have been identi-
ﬁ ed which seem to characterize different types of alcoholics.
(12)
One such group (type 1) tend to score low in novelty seeking and 
high in harm avoidance and reward dependence. Another group (type 2) is formed by the natural thrill seekers, who appear to ignore harmful consequences and punitive responses. This latter cluster, which prevails mostly in males with early-onset alcoholism, Box 4.2.2.1.1  A bio-psychosocial model of the aetiology of 
alcoholism
The comunity/sociocultural environment
X policies affecting availability and price (temperance, prohibition, 
taxation)
X cultural patterns of consumption, social acceptability of 
drinking/drunkenness

taxation)
X availability of other reinforcers (sources of pleasure/recreation)
X employment and/or educational opportunities (anomie/
marginalization)
X peer inﬂ  uences/role models (afﬁ  liation with deviant subculture)
The family environment
X marital breakdown (lower socio-economic status, poor paren-
tal monitoring)
X family attitudes (availability of drugs/alcohol, modelling of 
siblings/parents)
X intrauterine exposure to alcohol/drugs (potential effects of 
alcohol, nicotine and other drugs on behaviour and cognition)
X familial substance abuse (poverty, violence, and increased 
rates of early life trauma including neglect and physical/sexual abuse)
Individual/host factors
X heritable genetic factors (genetic loading for alcohol/drug 
dependence, depression, anxiety disorders in first-degree relatives)

X differences in response to alcohol (low sensitivity in terms of 
physiological responses and subjective effects)
X metabolic differences (thiamine deﬁ  ciency, alcohol metaboliz-
ing enzymes)
X high risk taking behaviours (male sex)
X childhood psychopathology (conduct disorder, untreated 
ADHD)
X psychiatric disorders (bipolar, depression, anxiety, schizophrenia) 4.2.2.1 aetiology of alcohol problems

SECTION 4  clinical syndromes of adult psychiatry 434
is also typical of antisocial personalities. Of all personality features, 
conduct disorder and antisocial behaviour are the strongest predic-tors of alcohol misuse.
(13)
(a) Psychodynamic processes
Early psychodynamic writings portrayed alcoholism and other addictions as regressive behaviours caused by unconscious conﬂ  icts 
over libidinal pleasures, homosexuality, and aggression. More recent formulations emphasize ego and self-developmental prob-lems, and consider psychoactive substance abuse as a response to psychological suffering; an attempt at re-establishing homeostasis. This is known as the self-medication hypothesis  of addictions,
(14)
according to which, persons with self-regulatory deﬁ  ciencies in 
the areas of self-care, self-esteem, self-object relations, and affect tolerance, would drink to palliate their distress.
(b) Learning

Alcohol abuse as seen by some as a behavioural pattern which has been learned through mechanisms of classical (i.e. Pavlovian) and operant conditioning. According to this interpretation, the perpet-uation of heavy drinking results from its association with condi-tioned stimuli (cues), and from the action of positive (pleasant effects) or negative (stress reduction) behavioural reinforcement. Additional components of this equation are the so-called alcohol ‘expectancies’ . Alcohol abusers tend to overemphasize the pleasant aspects of drinking and to ignore the negative ones; the learning theory of alcoholism assumes that such a cognitive set is also acquired through social exposure. The Social Learning Theory posits that the positive expectancy of relaxation following a drink can facilitate more frequent alcohol use and thus contribute to the development of dependence.
(15)
(c) Psychiatric comorbidity
Community and clinical epidemiology ﬁ  ndings point to the pres-

(15)
ence of other psychiatric disorders as one of the most signiﬁ  cant 
psychological risk factors in alcoholism.(16) The co-occurrence is 
sometimes sequential, with the psychiatric disorder preceding alcoholism; in which case a causal role in the development of heavy/frequent drinking is attributed to the former. While this is often observed in cases of conduct disorder, social phobia, atten-tion deﬁ  cit-hyperactivity (untreated) and depression, there are 
other psychiatric disturbances such as panic disorder, generalized anxiety and dysthymia that often become clinically signiﬁ  cant only 
after the person has been abusing alcohol for sometime. Thesealcohol-induced  mood and anxiety disorders represent a sizeable 
proportion of the comorbidity rates.
(17) Whether or not it is 
‘primary’ , psychological stress is a widely recognized factor in alcoholism treatment failure and relapse.

Y et the comorbidity of some psychiatric disorders (e.g. bipolar 
disorder, schizophrenia) and alcoholism appears to develop in no predictable sequence, so that if not random, their co-occurrence could be assumed to result from common genetic inﬂ  uences (see 
below) and pathophysiological mechanisms. One such interpreta-tion is the ‘reward deﬁ  ciency syndrome’ hypothesis; it purports that 
both psychiatric disturbances (e.g. negative symptoms of schizo-phrenia) and the tendency to abuse addictive substances arise from a basic dysfunction of the dopamine mesocorticolimbic reward system.
(18) The ‘primary addiction’ theory is another such explana-

tion for comorbidity; it contends that a single neurobiologicaldeﬁ ciency—primary abnormalities in the hippocampus and the frontal cortex—facilitate the development of schizophrenic symp-
toms and the person’s toxicophilia in a parallel manner.
(19)
Genetic factors in the development 
of alcoholism
In recent decades the biological perspective on the aetiology
of alcoholism has gained considerable ground. Findings fromfamily, twin and adoption studies demonstrate that there issigniﬁ  cantly higher risk for alcoholism among individuals with an 
alcoholic biological parent or ﬁ  rst-degree relative.
(20–23) Meta-

analysis has been used to jointly analyze data from twin andadoption studies grouped by country of origin (Scandinavianversus United States of America). Based on all available data,genetic factors accounted for between 40 and 60 per cent of the variance in alcoholism risk, with the effects of environment (shared and non-shared) estimated between 15 and 33 per cent. In a meth-odologically rigorous study, Prescott and Kendler
(24) examined the 
concordance for alcoholism among a population-based sample from the Virginia Twin Registry. Monozygotic (MZ, n = 861) and 
dizygotic (DZ, n = 653) male twins were diagnosed using structured 
interviews and DSM criteria. Concordance rates for alcohol depen-dence were signiﬁ  cantly higher for MZ (48 per cent) compared to 
DZ (32 per cent) twins, and analyses indicated that 48–58 per cent of the variation in alcoholism liability could be attributed toadditive genetic factors.

Alcoholic males with family history of alcoholism (FHP) have 
been reported to have greater severity of alcoholic symptoms and poorer outcomes than alcoholics that are family history negative (FHN). Box 4.2.2.1.2 describes some characteristics of familial alcoholism. Onset of drinking prior to age 15 is associated higher 
rates of alcoholism,
(25) ADHD, conduct and anxiety disorders, as 
well as a host of other negative events including unintentional inju-ries, physical ﬁ  ghts, nicotine/drug dependence, and poor school 
performance. Children of alcoholics are signiﬁ  cantly more likely to 
be exposed to high-risk environments that include poor prenatal care (alcohol/nicotine exposure, nutritional deﬁ  ciencies), as well as 
homes in which there is more poverty and violence. Overall, it

homes in which there is more poverty and violence. Overall, it 
Box 4.2.2.1.2  Characteristics of familial alcoholism
Family history positive (FHP) alcoholism is associated with:
X Earlier onset (<15 at age ﬁ  rst drink is associated with increased 
rates of alcoholism, nicotine dependence, drug use, andconduct disorder. Early age of alcohol use is familial, heritable and may be related to transmission of disinhibitory psychopa-thology in males)
X Behavioural disturbances during childhood (conduct
dis order, emotional lability, aggressivity, low attention span, low soothability)
X More severe alcohol dependence (higher levels of physical 
dependence, negative consequences)
X Lower educational and occupational achievement
X Deﬁ  cits in executive cognitive functioning (poor problem 
solving, abstraction, and perceptual-motor skills)

435
appears likely that there are common genetic and environmental 
inﬂ uences on a host of externalizing disorders—as well as gene–
environment interactions.
Linkage studies to identify the genes 
underlying the heritability of alcoholism
A number of large-scale international linkage studies are currently 
underway that are aimed at mapping genes for alcoholism includ-ing the Irish Affected Sib Pair Study,
(26) and the Collaborative Study 
on the Genetics of Alcoholism (COGA).(27) COGA is a multi-center

on the Genetics of Alcoholism (COGA).(27) COGA is a multi-center 
program designed to detect and map susceptibility genes for alcoholism that is currently underway in the United States. Using a family-based linkage strategy, the study is examining a number of quantitative intermediary phenotypes (endophenotypes) includ-ing P300 evoked potentials, alcohol sensitivity, and personality traits (harm avoidance, novelty seeking, and reward dependence) in relation to both alcohol consumption, and alcohol dependence. In addition, the study is examining the association between polymorphisms in speciﬁ  c candidate genes such as alcohol dehy-
drogenase (ADH), monoamine oxidase (MAO
B), and the serotonin 
transporter and alcohol-related phenotypes. In early work, COGA-reported associations between alcoholism and regions on chromosomes 4 and 15 that encode genes for the inhibitory neu-rotransmitter, gamma-aminobutyric acid (GABA
A). Most recently,

A). Most recently, 
linkage and association genome scans for a broader ‘addiction’ vulnerability phenotype provided strong evidence for linkage to chromosome 4. Further assessment of single nucleotide polymor-phism (SNP) genotypes within the chromosome 4 region provided strongest support for the involvement of the GABA
A receptor α2
subunit (GABRA2 gene).(28) GABAA has been implicated in medi-
ating some of the psychopharmacological effects of alcohol,(29) and 
the genetic studies provide convergent evidence suggesting that the predisposition to alcoholism may be inherited as a general state of CNS disinhibition/hyperexcitability that results from an altered responsiveness to GABA. However, this remains to be conﬁ  rmed by 
additional genetic and experimental studies.
Other candidate genes and processes
It has been shown that genetic factors may inﬂ  uence a number

It has been shown that genetic factors may inﬂ  uence a number 
of important processes such as initial sensitivity to the effects of alcohol, as well as the development of tolerance, sensitization, and physical dependence (including withdrawal complications such as seizures and delirium tremens). Several lines of research have sug-gested that sensitivity to alcohol may inﬂ  uence the propensity to 
abuse. Sensitivity refers to drug effects such as intoxication, physi-ological reactivity, and activation (tendency towards stimulation versus depression following ingestion). For example, Schuckit
(30,31)
found that individuals with low sensitivity to alcohol as measured by lower psychomotor responses and less subjective intoxication following alcohol dosing were more  likely to be alcohol dependent 
at follow-up 10 years later.
Peripheral and central levels of alcohol metabolizing enzymes

Peripheral and central levels of alcohol metabolizing enzymes 
may be important modulators of the psychopharmacological response to alcohol. Ethyl alcohol (ethanol) is converted to acetal-dehyde via the actions of alcohol dehydrogenase (ADH). There is evidence for linkage of gene(s) located on chromosome 4 (as dis-cussed above) and two ADH genes closely linked on chromosome 4 (ADH1B and ADH1C) that encode for isozymes that differ in their 
kinetic properties. The allele ADH1B*2 (found largely in individuals of East Asian and Jewish descent) encodes a more active isozyme that has been associated with protection from alcohol dependence. Most recently Edenberg et al.
(32) genotyped 110 SNPs across seven ADH

(32) genotyped 110 SNPs across seven ADH 
genes in a COGA sample. There was strong evidence that variations in ADH4 were associated with alcoholism, and among African-Americans there was evidence that the ADH1B*3 allele wasprotective. Acetaldehyde produced by ethanol oxidation is rapidly metabolized by the enzyme aldehyde dehydrogenase (ALDH). Asingle base pair substitution in mitochondrial ALDH, termed the ‘ori-ental’ mutation (ALDH2*2 allele), is present in a large percentage of the Asian population. This mutation renders the enzyme inactive and produces a flushing response (warm-flushed face, tachycardia,nausea) following ingestion of small quantities of alcohol due to the buildup of acetaldehyde, particularly among ALDH2*2 homozygotes. Due to the aversive nature of the ﬂ  ushing response, the ALDH2*2 
mutation is a signiﬁ  cant protective factor against alcoholism.
In addition to the examination of metabolic factors that may

In addition to the examination of metabolic factors that may 
account for some of the genetic variance in the development of alco-hol dependence, there is an intense search for other neurogenetic factors related to the effects of alcohol in the brain. As shown inBox 4.2.2.1.3, a large number of candidate markers and putative genetic loci that have been investigated to date. For example, absti-nent alcoholics and approximately 35 per cent of sons of alcoholics have been shown to have lower amplitude of a P300 event-related brain potential. Analyses of COGA data indicate that P300 ampli-tude reduction (P3-AR) is heritable, but more recent analyses have demonstrated that the P3-AR is associated with risk for substance dependence generally (e.g. frequent use of cannabis).
(33)
The analysis of various neurotransmitters (including synthesis,

(33)
The analysis of various neurotransmitters (including synthesis, 
release, receptor density, second messengers, polymorphisms) in relation to alcoholism and other alcohol-related endophenotypes is a well-developed area of research. The high degree of comorbidity between alcoholism and other mental disorders suggests that there may be common neurobiological pathways, including those that Box 4.2.2.1.3  Potential candidate genes and markers for 
X Brain waves (P300 event-related brain potential)
X Brain enzymes (e.g. monoamine oxidase, adenylate cyclase)
X Alcohol and aldehyde metabolizing enzymes (ADH, catalase, 
ALDH, cytochrome P450IIE1)
X Opioids (e.g. kappa OPRK1receptor and prodynorphin 
ligand)
X Serotonin (e.g. polymorphisms of the 5-HT transporter and 
receptors (e.g. 5-HT1B, 5-HT2A, 5-HT2C), tryptophan hydroxylase TPH (218AC))
X Dopamine (polymorphisms of D2, D3, D4 receptors and the 
dopamine transporter (DAT))

X GABA (polymorphisms in receptor subunits, variants in 
glutamate decarboxylase-2 ( GAD2 ))
**Note that this list is not exhaustive. For a more complete review 
consult references 32–5.**4.2.2.1 aetiology of alcohol problems

SECTION 4  clinical syndromes of adult psychiatry 436
modulate reward, compulsive behaviour, anxiety, depression, and 
stress responses.(34) In this context, dysregulation of the serotonin 
(5HT) system has been implicated in the aetiology of a number of psychiatric disorders (depression, OCD, eating disorders) and alcoholism. In particular, polymorphisms in the promoter region of the 5HT transporter (5HTTLPR) producing the short (‘S’ allele) or long (‘L’ allele) variants differentially modulate transcriptional activity of the promoter, yielding differences in 5HT uptake activity in human platelets and brain. Most recently analyses conducted in the COGA sample have failed to ﬁ  nd an association between the 
5HTTLPR polymorphism and alcohol dependence. In a family-based association analyses ( n = 1913 Caucasians) there was 
evidence for association of the S allele with depression, but not with alcohol dependence.
(27)
Numerous studies have examined the association between alco-

(27)
hol dependence and the A1 allele of the dopamine D2 receptor (DRD2), however results have been debated for more than a decade. In general, the A1 allele is not consistently associated with alcohol-ism, and it does not consistently co-segregate in families with alcoholism. The effect size of this allele is likely to be very small. The human genes for the dopamine D3 and D4 receptors are polymorphic and studies are currently underway examining the potential relationship between various alleles of these receptors and substance dependence.
As noted above, synaptic actions of GABA have been implicated 
in the psychopharmacological effects of alcohol. Associations between variants in glutamate decarboxylase-2 ( GAD2 ), a gene

in the psychopharmacological effects of alcohol. Associations between variants in glutamate decarboxylase-2 ( GAD2 ), a gene 
encoding for a major enzyme in the synthesis of GABA have been reported. In particular a functional promoter GAD2  -243 A > G 
variant may inﬂ  uence risk for alcohol dependence in populations 
exhibiting severe alcoholism.
(35)
In summary, plausible candidate genes for alcoholism include 
loci associated with alcohol and aldehyde metabolism, as well as variants within the GABA, opiate, and serotonin systems. The strongest candidate to date is for the involvement of the GABA
A
receptor α2 subunit (GABRA2 gene) on chromosome 4. Notably,

A
receptor α2 subunit (GABRA2 gene) on chromosome 4. Notably, 
associations between various loci and alcoholism reported in the literature have not been consistently replicated. Discrepancies in the literature have beesn attributed to variations in sampling (ethnicity, diagnostic criteria, severity of alcoholism, sample sizes), as well as to the clinical and genetic heterogeneity of alcoholism. Thus in this context, it is important to note that possible mecha-nisms for indirect transmission of an alcoholism phenotype include personality traits, and comorbid psychopathology including anxiety, depression, and conduct disorder.
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4.2.2.2 Alcohol dependence 
and alcohol problems
The problem of excessive alcohol consumption is a major cause of 
public health concern in most countries of the world today. Heavy consumption, which involves far more than ‘dependence’ , can cause untold misery to the individual, who is usually affected by other physical, psychological, and social disabilities as well.
As early as 1950, the World Health Organization (WHO) viewed

As early as 1950, the World Health Organization (WHO) viewed 
the lack of a commonly accepted terminology as a serious obstacle to international action in the alcohol ﬁ  eld.
(1)
Deﬁ nitions of ‘alcoholism’ have been proposed by a range of 
professional and other bodies, from biomedical scientists, medical doctors and psychiatrists, psychologists, sociologists, patients in treatment, to the general public.
(2) T erms such as ‘alcoholism’ , ‘addic-
tion’ , and ‘chemical dependence’ , have passed into everyday speech, becoming ‘popularly enriched’ and ‘technically impoverished’ .
(2)
These terms mean different things to different people and often have pejorative connotations. The lack of a precise deﬁ  nition of ‘drinking 
problems’ has hampered interdisciplinary communication.In this section, the evolution of the term ‘alcohol dependence’

problems’ has hampered interdisciplinary communication.In this section, the evolution of the term ‘alcohol dependence’ 
will be traced and put into context as but one aspect of a wider spectrum of alcohol-related problems. The concept of the alcohol dependence syndrome (ADS)
(3) will be introduced and its
inﬂ uence on the 10th revision of the International Classiﬁ  cation
of Diseases  (ICD-10)(4) and the fourth edition of the Diagnostic
and Statistical Manual of Diseases  (DSM-IV) will be reviewed.(5)
The terms ‘harmful use’ (ICD-10) and ‘alcohol abuse’ (DSM-IV) 
will also be discussed. Finally ‘alcohol-related problems’ will be considered.
The development of classiﬁ  cation systems 
for alcohol use disorders
From the time of its inception in 1948, WHO played a major role in 
formulating public health deﬁ  nitions of ‘alcoholism’ , ‘addiction’ , 
and ‘dependence’ through a series of expert committees. Early deﬁ  -

nitions stressed the sociological rather than the physical aspects of dependence, and thus had limited utility for biological research and psychiatric classiﬁ  cation.
‘Alcoholism’ was classiﬁ  ed under ‘Other non-psychotic mental 
disorders’ in ICD-8.
(6) This deﬁ  nition of ‘alcoholism’ was generic, 
and included the subcategories of episodic excessive drinking, habitual excessive drinking, and alcohol addiction. Alcohol addic-tion was deﬁ  ned as:
(6)
a state of physical and emotional dependence on regular or periodic, 
heavy, and uncontrolled alcohol consumption, during which the per-son experiences a compulsion to drink. On cessation of alcohol intake there are withdrawal symptoms, which may be severe.
In ICD-9 the term ‘alcoholism’ was dropped in favour of the 
‘alcohol dependence syndrome’ .(7) It was, however, still classiﬁ  ed

‘alcohol dependence syndrome’ .(7) It was, however, still classiﬁ  ed 
under the category ‘Other non-psychotic mental disorders’ .
At the same time as WHO was formulating public health
deﬁ nitions of ‘alcoholism’ , ‘addiction’ , and ‘dependence’ , a trend 
towards formal diagnostic criteria was emerging in the United States. This was driven by practical considerations such as the need for better communication between clinicians, researchers, and the general public. Other inﬂ  uential factors included the growing need 
to categorize persons in an objective fashion for legal, medical, or psychiatric reasons, to collect and communicate accurate public health information, and to standardize practice nationally and internationally. The first two editions of the Diagnostic and 
Statistical Manual (DSM-I and DSM-II ), published in 1952 and 
1968 respectively, classiﬁ  ed ‘alcoholism’ as a category of personality

1968 respectively, classiﬁ  ed ‘alcoholism’ as a category of personality 
disorder. In DSM-III,
(8) it was included under a new and separate 
category of ‘Substance use disorders’ . The terms ‘alcoholism’ and ‘addiction’ were dropped and the terms ‘dependence’ and ‘alcohol abuse’ were used instead. Dependence was distinguished from abuse by the presence of tolerance or withdrawal symptoms.
By the mid-1980s, DSM-III and ICD-9 were undergoing reviews
for the purposes of revision. The diagnostic criteria for dependence were broadened in DSM-IIIR
(9) to incorporate the elements of the 
alcohol dependence syndrome as hypothesized by Edwards and Gross.
(3) The essential feature of the DSM-IIIR dependence catego-
ry was deﬁ  ned in the text as a ‘cluster of cognitive, behavioural, and

ry was deﬁ  ned in the text as a ‘cluster of cognitive, behavioural, and 
physiological  symptoms, indicating that the person has impaired control over drinking and continues to drink despite adverseconsequences’ .4.2.2.2 alcohol dependence and alcohol problems

SECTION 4  clinical syndromes of adult psychiatry 438
The alcohol dependence syndrome
Clinical description
In 1976, Edwards and Gross proposed the existence of alcohol depen-
dence within a syndrome model.(3) Their description was based on 
the clinical observation that certain heavy drinkers manifested an interrelated clustering of signs and symptoms. They hypothesized that dependence was not an all-or-nothing phenomenon but e xisted 
in degrees of severity. The elements of the syndrome, as orig inally 
formulated, are summarized in Table 4.2.2.2.1. Not all the elements need always be present, nor always present with the same intensity. Edwards and Gross
(3) also acknowledged the fact that not everyone 
who drinks too much is necessarily dependent on alcohol. They hypothesized that alcohol dependence should be conceptually dis-tinguished from alcohol-related problems.
By drawing a clear distinction between the alcohol dependence

By drawing a clear distinction between the alcohol dependence 
syndrome and alcohol-related problems, Edwards and Gross intro-duced the concept of a bi-axial model. This was described further in the report of a WHO scientiﬁ  c group published in 1977.
(10) Alcohol-
related problems are deﬁ  ned as comprising those physical, psycho-
logical, and social problems that are a consequence of excessivedrinking and dependence. Consumption may be viewed on a third axis.
The alcohol dependence syndrome was proposed in the ﬁ  rst 
instance as an empirical formulation that would require research to conﬁ  rm its assumptions. Unlike previous models of ‘alcoholism’ 
that had observational elements but no theoretical input, the alco-hol dependence syndrome was inﬂ  uenced by psychological theory 
and proposed as a synthesis of both general learning theory and speciﬁ  c conditioning models of dependence.
(11,12)
Establishment of the validity of the alcohol 
dependence syndrome

(11,12)
A considerable amount of scientiﬁ  c research evaluating the ADS 
has been carried out over the past 30 years, much of it supporting its validity.
(13) Studies have focused on the degree to which the 
elements of the syndrome co-occur.(14,15)  Other areas of research 
have included construct validity,(16) concurrent validity,(15,17,18)
and predictive validity.(19,20)  Field trials conducted as background 
to the preparation of ICD-10, DSM-IIIR, and DSM-IV , have all contributed to the body of research evidence.
(5, 21–25)  Difﬁ  culties 
have been encountered in operationalizing elements such asnarrowing of repertoire, subjective change, and reinstatement.
(25)
These studies have shown a remarkable similarity in terms of

(25)
the coherence and dimensionality of the syndrome, and areparticularly impressive because of the diversity of methods and populations used.
(11)Individual elements of the alcohol dependence 
syndrome
(a) Narrowing of the drinking repertoire
Most drinkers vary their alcohol consumption from day to day and 
week to week. The pattern of their drinking is inﬂ  uenced by a range

syndrome
week to week. The pattern of their drinking is inﬂ  uenced by a range 
of internal cues and external circumstances. Heavy drinkers may initially widen their drinking repertoire. As dependence advances, so a diminished variability in drinking behaviour emerges. The dependent person begins to drink in the same manner every day. The daily pattern established ensures that a relatively high blood-alcohol level is maintained and that symptoms of alcohol with-drawal are avoided. As drinking becomes stereotyped with advanced 
dependence, dependent drinkers are able to describe their drinking 
day in minute detail.
(b) Salience of drinking-seeking behaviour

With advancing dependence, individuals give priority to maintain-ing their alcohol intake. Alcohol consumption is maintained despite painful direct consequences such as physical illness, rejection by family, and lack of money. They will ‘beg, borrow, or steal’ to obtain money for alcohol.
(3)
(c) Increased tolerance to alcohol
Regular drinkers become tolerant to the central nervous system effects of alcohol and can sustain blood alcohol levels thatwould incapacitate the non-tolerant drinker. In short, they can ‘drink others under the table’ . T olerance may decrease in thelater stages of dependence, with individuals becoming intoxicated on much less alcohol than would previously have affected them. Cross-tolerance extends to other drugs, notably barbiturates and benzodiazepines.
(d) Withdrawal symptoms

The term ‘alcohol withdrawal’ describes a broad range of symptoms and signs, from the relatively trivial to the life-threatening. At ﬁ  rst 
the symptoms are intermittent and mild, but as the degree of depen-dence increases, so do the frequency and intensity of withdrawal symptoms. Symptoms vary from person to person and do notrequire abstinence to appear; they can occur when blood-alcohol concentrations are falling. When the picture is fully developed, the dependent drinker typically has severe multiple symptoms every morning on waking; these symptoms may wake him in the middleof the night. Those who are severely dependent usually experience mild withdrawal symptoms during the day whenever their alcohol levels fall.
Withdrawal symptoms cannot occur without a high degree of 
central nervous system tolerance, but tolerance can occur without 
clinically manifest withdrawal symptoms.
(3)
The spectrum of symptoms is wide, but the four key symptoms

(3)
The spectrum of symptoms is wide, but the four key symptoms 
are tremor, nausea, sweating, and mood disturbance. A range of other symptoms can also occur, including sensitivity to sound (hyperacusis), ringing in the ears (tinnitus), itching, muscle cramps, sleep disturbance, perceptual distortion, hallucinations, generalized (grand mal) seizures, and delirium tremens.
The four key symptoms will be described in further detail.
(i) Tremor
The ﬁ  rst experience of alcohol withdrawal tremor may be recalled 
vividly: ‘One afternoon I went to cut the grass at a friend’s house. She gave me a cup of tea and my hands kept shaking. I kept rattling Table 4.2.2.2.1 Key elements of the alcohol dependence syndrome
Narrowing of repertoire
Salience of drinking
Increased tolerance to alcohol
Withdrawal symptomsRelief or avoidance of withdrawal symptoms by further drinking

Subjective awareness of compulsion to drink
Reinstatement after abstinence
Reproduced from G. Edwards and M. M. Gross (1976). Alcohol dependence: provisional 
description of a clinical syndrome. British Medical Journal  1, 1058–61, copyright 1976, BMJ 
Publishing Group Ltd.

439
the cup on the saucer and couldn’t put the cup to my mouth. I had 
to put them down and pretend that I had ﬁ  nished.’ Men often ﬁ  nd 
it difﬁ  cult to shave ﬁ  rst thing in the morning and merely getting 
the ﬁ  rst drink of the day to the mouth may be an ordeal in itself.
(ii) Nausea
Dependent drinkers commonly say that their bodies want to 
vomit ﬁ  rst thing in the morning, but that they have nothing to 
bring up. This may be described as ‘dry retching’ or ‘the dry heaves’ . Typically they ﬁ  nd it difﬁ  cult to eat breakfast and to brush their 
teeth. The ﬁ  rst drink of the day is often vomited back.
(iii) Sweating
Dependent drinkers commonly describe waking up in the early 
morning (3 a.m. or 4 a.m.) to ﬁ  nd the bed sheets ‘drenched’ . In the 
earlier stages of dependence they may report feeling clammy.
(iv) Mood disturbance

This is an important feature of the withdrawal syndrome. Mildly dependent individuals may feel ‘a bit edgy’ . Severely dependent individuals may present with clinically signiﬁ  cant symptoms of 
anxiety and depression.
(e)  Relief or avoidance of withdrawal symptoms by further 
drinking
In the early stages of dependence, individuals may ﬁ  nd that they 
need a lunchtime drink to alleviate discomfort. As dependence progresses there emerges the need for an early morning drink to relieve the symptoms of alcohol withdrawal coming on after a night’s abstinence. Later, individuals may wake in the middle of the night for a drink, and alcohol is often kept by the bed. If they have to go for 3 or 4 hr without a drink during the day, they value the next drink for its relief effect.

Clues to the degree of dependence can be obtained by taking a 
detailed history of the ﬁ  rst drink of the day. The person drinking 
from a bottle kept by the side of the bed before they get up ismore dependent than the person who has breakfast and readsthe paper ﬁ  rst. The woman who pours whisky into her ﬁ  rst cup of 
tea is more dependent than the librarian who slips out to the
lavatory at midday to drink from a quarter bottle of vodka hidden 
in her handbag.
(f) Subjective awareness of compulsion to drink
This describes an altered subjective experience of an inability to limit drinking to an acceptable level. Although the familiar term ‘loss of control’ has been used to denote this element, it is more likely that control has been ‘impaired’ rather than lost.
Another complex experience is that of ‘craving’ , the subjective

Another complex experience is that of ‘craving’ , the subjective 
experience of which is greatly influenced by environment. Individuals can experience craving of very different intensities on different occasions. Cues for craving include the experience of intoxication, the withdrawal syndrome, mood (anger, depression, elation), or situational cues (being in a pub or (bar), passing an off-licence (liquor store).
Here the key experience may best be described as a compulsion 
to drink. The desire for a further drink is seen as irrational, and is resisted, but despite this a further drink is taken.
(g) Reinstatement after abstinence
Alcohol dependent individuals who begin to drink again after a period of abstinence invariably relapse back into the previous stage of the dependence syndrome. This process occurs over a variable time course, with moderately dependent individuals perhaps tak-
ing weeks or months and severely dependent individuals taking a couple of days.

Inﬂ uence of the alcohol dependence 
syndrome on ICD-10 and DSM-IV
Both DSM-IV and ICD-10 diagnostic approaches have drawn on 
the original concept of the alcohol dependence syndrome.(26,27)
Although they have undoubtedly contributed to the standardiza-tion of psychiatric practice nationally and internationally, they picture dependence as an all-or-nothing phenomenon rather than as a dimensional state.
(28)
ICD-10(4)
ICD-10 includes six items under dependence, most of which are similar to DSM-IV . For a diagnosis of dependence, three or more items should have occurred in the past year. The ‘strong desire or sense of compulsion to take the substance’ is viewed as a central descriptive characteristic of dependence in ICD-10. This compulsive-use indicator is not included in the DSM-IV concept of dependence (Table 4.2.2.2.2).
DSM-IV(5)

DSM-IV(5)
In view of the major changes in criteria that had occurred between 1980 and 1987, the DSM-IV Substance Use Disorders Work Group was reluctant to make any additional major changes to DSM-IIIR. The repetitive nature of the problem was highlighted in that three or more of the items should have occurred during the same 12-month period and the associated difﬁ  culties must have led to 
clinically signiﬁ  cant impairment or distress. DSM-IV also uniquely 
allows for the subtyping of dependence with and without physio-logical dependence (Table 4.2.2.2.2).
Alcohol abuse and harmful use
Alcohol abuse
DSM-III; DSM-IIIR; DSM-IV
The term ‘alcohol abuse’ appeared infrequently in the American
literature before 1970, when the United States National Instituteon Alcohol Abuse and Alcoholism was formed. It was adoptedas a formal diagnostic category by DSM-III,
(8) which deﬁ  ned abuse

(8) which deﬁ  ned abuse 
as a behavioural concept: ‘A pattern of pathological use for atleast a month that causes impairment in social or occupational functioning’ . Although enshrined in DSM-IIIR and DSM-IV ,the term ‘abuse’ has been variously regarded as ‘unscientiﬁ  c and 
pejorative’
(29) and ‘oppobrious’ and ‘vindictive’ .(30)
The DSM-IV Substance Use Disorders Workgroup carried out 
extensive analysis in an effort to define abuse more precisely. Accordingly, in DSM-IV , four separate items, not included independence, are listed for the diagnosis of abuse, focusing on social, physical, legal, and interpersonal problems associated with alcoholuse. These problems must have occurred repeatedly over a 12-month period, and caused ‘clinically signiﬁ  cant impairment or distress’ (Table

4.2.2.2.3). In practice, the DSM-IV alcohol abuse deﬁ  nition includes
a mixture of dependence and harm criteria which could be scaled along a single continuum of severity of alcohol dependence.4.2.2.2 alcohol dependence and alcohol problems

SECTION 4  clinical syndromes of adult psychiatry 440
Harmful use
(a) ICD-10
The ICD-10 criteria for harmful use of alcohol differ signiﬁ  cantly 
from the DSM-IV abuse classiﬁ  cation. An ICD-10 diagnosis of 
harmful drinking requires a pattern of drinking that has caused actual physical or psychological harm to the user. This deﬁ  nition 
excludes social harms such as marital problems and does not over-lap with the DSM-IV deﬁ  nition of alcohol abuse.
The future
Revision of the DSM and ICD classiﬁ  cation systems must address the 
fact that the current systems do not address the continuum of severity of alcohol use disorders (AUDs). Research is needed to explore the relationship between AUDs and the quantity, frequency, and pattern of drinking.
(31) Further reﬁ  nements of the alcohol dependence diag-
nosis should focus on the essential or core features of the disorder.
Alcohol-related problems

Not everyone experiencing an alcohol problem or alcohol-related disability will be suffering from alcohol dependence. Both dependent and non-dependent drinkers, particularly binge drinkers, are at risk of problems related to heavy alcohol consumption. Indeed, epi-demiological evidence supports the view that most alcohol-related Table 4.2.2.2.2  Comparison of ICD-10 and DSM-IV criteria for substance dependence
ICD-10 DSM-IV
A diagnosis of dependence should usually be made only if three or 
more of the following have been experienced or exhibited at some 
time during the previous year:
Evidence of tolerance such that increased doses of the psychoactive 
substance are required in order to achieve effects originally produced 
by lower doses
A physiological withdrawal state when substance use has ceased or 
been reduced, as evidenced by:

X the characteristic withdrawal syndrome for the substance or
X  use of the same (or a closely related) substance with the intention 
of relieving or avoiding withdrawal symptoms
A strong desire or sense of compulsion to take the substanceNo equivalent criterionDifﬁ  culties in controlling substance-taking behaviour in terms of its 
onset, termination, or levels of use
Progressive neglect of alternative pleasures or interests because of 
psychoactive substance use
Increased amount of time necessary to obtain or take the substance or 
recover from its effects
Persisting with substance use despite clear evidence of overtly harmful 
consequences. Efforts should be made to determine that the user was actually, or could be expected to be, aware of the nature and extent of

consequences. Efforts should be made to determine that the user was actually, or could be expected to be, aware of the nature and extent of 
the harmA maladaptive pattern of substance use, leading to clinically signiﬁ  cant impairment or 
distress, as manifested by three (or more) of the following at any time in the same 12-month period
Tolerance as deﬁ  ned by either of the following:
X  need for markedly increased amounts of the substance to achieve intoxication or 
desired effect
X  markedly diminished effect with continued use of the same amount of substance
Withdrawal as manifested by either of the following:
X the characteristic withdrawal syndrome for the substance
X  the same (or closely related) substance is taken to relieve or avoid withdrawal symptoms
No equivalent criterion
There is a persistent desire or unsuccessful efforts to cut down or control substance use
The substance is often taken in larger amounts or over a longer period than was intended

Important social, occupation or recreational activities are given up or reduced because of 
A great deal of time is spent in activities necessary to obtain the substance, use the 
substance, or recover from its effects
The substance use is continued despite knowledge of having a persistent or recurrent 
physical and psychological problem likely to have been caused or exacerbated by the 
substance.
Specify if:
With Physiological Dependence:  evidence of tolerance or withdrawal (either item is present)
Without Physiological Dependence:  no evidence of tolerance or withdrawal
Reproduced from ICD-10 and DSM-IV.(4, 5)
Table 4.2.2.2.3  Comparison of criteria for abuse or harmful use of 
ICD-10 criteria for harmful use

A pattern of psychoactive substance use that is causing damage to health, 
either physical or mental. The diagnosis requires that actual damage should 
have been caused to the mental or physical health of the user. Socially negative 
consequences, or the disapproval of others are not in themselves evidence of harmful use.
Harmful use should not be diagnosed if dependence syndrome, a psychotic 
disorder or another speciﬁ  c form of alcohol-related disorder is present.
DSM-IV criteria for substance abuse
A.
A maladaptive pattern of substance use leading to clinically signiﬁ  cant 
impairment or distress by one (or more) of the following occurring within a 
12-month period:
X  Recurrent substance use resulting in a failure to fulﬁ  ll major role obligations 
at work, school or home

X Recurrent substance use in situations in which it is physically hazardous
X Recurrent substance-related legal problems
X  Continued substance use despite having persistent or recurrent social 
or interpersonal problems caused or exacerbated by the effects of the 
substance
B.The symptoms have never met criteria for substance dependence

441
harm in the general population occurs in heavy non-dependent 
drinkers.
Alcohol-related problems are extremely diverse. They have been 
deﬁ ned as ‘those problems that may arise in individuals around 
their use of beverage alcohol, and that may require an appropriate treatment response for their optimum management’ .
(32) The phras-
es ‘alcohol problems’ or ‘alcohol-related problem’ contain an assumption of causality.
(33) This issue is a complex one, involving 
individual differences and the social context of drinking as well as the pattern, duration, and intensity of alcohol use.
Alcohol-related problems can be related to the acute or chronic

Alcohol-related problems can be related to the acute or chronic 
consumption of alcohol. A fractured ankle sustained by falling over while acutely intoxicated is an example of the former category. Cirrhosis of the liver is an example of a chronic problem. An indi-vidual who drinks in binges will experience different problems compared with someone who drinks the same amount of alcohol spread out over a week or a month or a year. The way in which a person behaves while intoxicated is another important factor determining the nature of alcohol-related problems. The social consequences of drinking such as job loss, imprisonment, marital and family break-up, and drunk-driving have profound effects on the well being of the drinker, their family, and society.
(33)
Types of alcohol-related problems
Although somewhat artiﬁ  cial, it is helpful to classify alcohol-related

(33)
Although somewhat artiﬁ  cial, it is helpful to classify alcohol-related 
problems in individuals into physical, psychological, and social categories. There is often considerable overlap between these three areas. The more severe the dependence, the greater the likelihood of problems of all three kinds.
(18)
Alcohol-related physical and psychological problems are discussed 
in the next section. Some of the social problems can be included here, for example the acute adverse consequences of drinking such as trauma resulting from road trafﬁ  c accidents, injuries from ﬁ  ghts, and 
death from overdose.
(33)
The social problems that can result from drinking are legion. 
Alcohol is involved in all types of accidents and contributes to trafﬁ  c deaths, home, and leisure injuries.
(33) It is associated with

(33) It is associated with 
domestic violence, child abuse, crime, homicide, and suicide and is also related to poor work performance, dismissal, unemployment, debt and housing problems, and crimes of violence.
There is a continuity between moderate and excessive drinking 
and between harmless drinking and drinking that results in harm or in problems. Such problem-clustering may reﬂ  ect alcohol depen-
dence, certainly amongst a proportion of these drinkers. Given this heterogeneity, no one form of treatment is likely to be effective for all individuals with alcohol problems.
(32) A range of treatments is 
required and it should be possible for non-specialists to offer brief interventions (see Chapter 4.2.2.4).
The study of alcohol-related problems remains underdeveloped, 
compared with the study of alcohol dependence.
(34) There may be

(34) There may be 
several reasons for this, not least the difﬁ  culties inherent in mea-
suring alcohol-related problems. Another important issue, central to these difﬁ  culties, is the extent to which alcohol is causally related 
to the problem.
Several questionnaires, measuring a variety of alcohol-related 
problems, have been developed. The Alcohol Problems Quest-ionnaire (APQ)
(34) is a standardized inventory, which includes
46 items covering eight problem domains: physical, psychological, friends, ﬁ  nances, police, marital, children, and work. All questions apply to the 6-month period prior to the completion of the
questionnaire. The shorter or core version includes the firstﬁ ve domains (23 items). This questionnaire can make a useful
contribution to the overall assessment, and is of potential value in outcome research.

An understanding of the concepts of alcohol dependence and alcohol-related problems is central to the therapeutic process with individual patients.
The development of diagnostic criteria has helped to standardize 
practice nationally and internationally, and aided interdisciplinary communication. The diagnostic criteria for dependence are imper-fect because they view the syndrome as an all-or-nothing phenom-enon rather than as a dimensional state. The concepts of abuse and harmful use need further reﬁ  nement. The totality of alcohol 
problems is a vast area with major implications for the general population, not just dependent drinkers.
Reports and reviews
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and treatment. Chapter 2 describes the categories of alcohol misuse, 
and sets them in the context of treatment and interventions to reduce alcohol-related harm.
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101, 1–173. A series of 18 articles commissioned by the Substance 
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Manual of Mental Disorders (DSM-V).

Marshall E. J, Farrell, M. Chapter editors. Addiction Psychiatry. Psychiatry, 5,
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4.2.2.3 Alcohol and psychiatric 
and physical disorders
Intoxication
Clinical symptoms of alcohol intoxication are associated with both, 
blood alcohol concentration ( BAC ), and the individual’s level of 
tolerance. Whereas in healthy persons without alcohol tolerance mild intoxication (BAC ≤ 100 mg per cent), medium intoxication

tolerance. Whereas in healthy persons without alcohol tolerance mild intoxication (BAC ≤ 100 mg per cent), medium intoxication 
(BAC 100–200 mg per cent), and severe intoxication (BAC >200 mg per cent) differ clinically, this schema does not work in patients suffering from alcoholism. In these people, different levels of tolerance can lead to completely different clinical pictures despite their having similar blood alcohol concentrations. Thus, psychopa-thology is more important than blood alcohol concentrations for estimating the severity of an acute intoxication state. With increasing BAC we observe elated mood, disinhibition, impaired judgement, belligerence, impaired social and occupational func-tioning, mood lability, cognitive impairment, reduced attention span, slurred speech, incoordination, unsteady gait, nystagmus, 
and stupor or coma.
The term ‘pathological intoxication’ can still be found in the older

The term ‘pathological intoxication’ can still be found in the older 
literature (reviewed by Lishman
(1)). It was described as an outburst 
of aggression and uncontrollable rage, which might have led to seri-ous destructions. As a rule, this behaviour, which was not typical for the individual, ended in terminal sleep and subsequent amnesia. However, since there is not enough empirical evidence for the exis-tence of this syndrome, it was no longer considered in DSM-IV .
(2)

443
Alcohol-induced amnesias (‘blackouts’)
This term refers to a transient state of amnesia after drinking excess. 
Usually patients’ behaviour is no different from their behaviour during other periods of intoxication without blackouts. Nevertheless, the memory gap usually lasts for hours, but may be as long as a day or more. In extreme cases, patients ﬁ  nd themselves in 
strange places with no recollection of how they got there.
Withdrawal without complications
When alcohol is used regularly and withdrawn rapidly, a character-istic withdrawal syndrome can develop. It includes autonomic hyperactivity like hand tremor, insomnia, sweating, tachycardia, hypertension, and anxiety. The symptoms generally occur between 6 and 12 h after the last alcohol consumption. Depending on their severity they may last for up to 4 or 5 days. The neurobiological basis for withdrawal is a gradual upregulation of N-methyl- d-
aspartate receptors under the inﬂ  uence of chronic alcohol use.

aspartate receptors under the inﬂ  uence of chronic alcohol use. 
As soon as the alcohol, which acts as a central nervous system depressant, is withdrawn, an overwhelming excitatory action in the brain mediated by the glutamatergic system is observed.
Withdrawal with perceptual disturbances
The individual usually experiences more discomfort and anxiety if transient visual, tactile, or auditory hallucinations or illusions are present. In this state, reality testing is still intact: the person still knows that the hallucinations are induced by the substance. If this is no longer true, a substance-induced psychotic disorder or a delirium tremens is likely.
Withdrawal with grand mal seizures (alcoholic 
convulsions, ‘rum ﬁ  ts’)
In about 30 per cent of the cases the typical grand mal seizures 
are followed by a delirium tremens. The electroencephalograph picture is only abnormal at the time of the ﬁ  ts, hence, alcohol con-
vulsions differ pathophysiologically from latent epilepsy.

Alcohol-induced psychosis (delirium tremens)

In delirium tremens the symptoms of alcohol withdrawal described earlier are accompanied by a reduced level of consciousness, disorientation in time and place, impairment of recent memory, insomnia, and perceptual disturbances. The latter include misin-terpretation of sensory stimuli and hallucinations; most are visual, but auditory and haptic hallucinations also occur. The hallucina-tions may be Lilliputian or of normal size, and may be of complex, frightening, and extremely realistic scenes. The patient is restless and fearful, and may become severely agitated. There is marked tremor, and ataxia when standing. Some patients experience vestibular disturbance. Autonomic disturbance includes sweating, tachycardia, raised blood pressure, and dilated pupils. There may be a mild pyrexia. Patients are usually dehydrated, often with abnormal electrolytes, leucocytosis, and impaired liver function.

As in other forms of delirium, symptoms are worse at night.
Delirium tremens is the most severe of the states following
withdrawal of alcohol, with a reported mortality of up to 5 per cent. In its fully developed form it is uncommon; the morefrequent states are acute tremulousness, transient hallucinations with tremor, and uncomplicated ﬁ  ts. Delirium tremens usually begins

after 3 to 4 days of abstinence from alcohol, although occasionally it starts while drinking continues. In the latter cases it is assumed that alcohol levels have fallen below a critical level. It is not known by what mechanism alcohol withdrawal leads to the clinical syndrome. Delirium tremens often appears to start suddenly, although close enquiry may reveal a prodromal stage of restlessness, anxiety, and insomnia. It usually lasts for 2 to 3 days, often ending with deep and prolonged sleep from which thepatient wakes symptom free andwith little memory of the period of delirium. Rarely, the patient is left with an amnesic syndrome, perhaps the consequence of previous undetected Wernicke’s encephalopathy.
Treatment is by sedation, usually with a benzodiazepine, together 
with ﬂ  uid replacement under close observation. The possibility of

with ﬂ  uid replacement under close observation. The possibility of 
accompanying head injury or infection should be investigated. Sedation should be adequate to prevent withdrawal seizures, with frequent monitoring of the response. High-potency vitaminsare usually given to prevent Wernicke’s encephalopathy. Ananticonvulsant is given when there have been withdrawal seizures in the past. Cardiovascular collapse and hyperthermia occuroccasionally and require urgent medical treatment.
Hallucinosis

Alcoholic hallucinosis is a rare condition in which auditory halluci-nations are present in clear consciousness and without autonomic overactivity, usually in a person who has been drinking excessively for many years. The hallucinations often begin as simple noises, but are gradually replaced by voices, which may threaten, abuse, or reproach the person. Usually the voices speak to the person, but sometimes they discuss him or her in the third person. The voices may be occasional or relentlessly persistent. They may command the patient, who may respond with unrestrained or suicidal behaviour. Delusions are secondary interpretations of the halluci-nations. Autochthonous hallucinations suggest schizophrenia, as do thought disorder or incongruity of affect. The patient is usually distressed, anxious, and restless.
In both ICD-10 and DSM-IV , the disorder is classiﬁ  ed as a 
substance-induced psychotic disorder and not, as has been suggest-

ed in the past, a form of schizophrenia (released by heavy drinking). The differential diagnosis includes transient auditory hallucinations occurring during withdrawal from a period of heavy drinking, and delirium tremens in which auditory hallucinations may accompany the more prominent visual ones. In both conditions the auditory hallucinations are transient and disorganized, and in the latter con-sciousness is impaired. In contrast, the auditory hallucinations of an alcoholic hallucinosis are persistent and organized, and occur in clear consciousness. Other differential diagnoses are depressive dis-order with psychotic symptoms and schizophrenia, both of which can be accompanied by heavy drinking.
The hallucinations usually respond rapidly to antipsychotic

The hallucinations usually respond rapidly to antipsychotic 
medication. The prognosis is good; usually the condition improves within days or a couple of weeks provided that the person remains abstinent. Symptoms that last for 6 months generally continuefor years.
(3)
Psychiatric disorders
Alcohol-dependent patients often present with symptoms of anxiety or depression. These states are generally referred to as 4.2.2.3 alcohol and psychiatric and physical disorders

SECTION 4  clinical syndromes of adult psychiatry 444
comorbid disorders or dual diagnosis. Alcoholism can be a conse-
quence of anxiety and mood disorders (‘secondary alcoholism’). It can develop independently after anxiety and depression,or it can precede anxiety and depressive symptoms (‘primary’).As the former are discussed elsewhere in this textbook, here we concentrate on the latter.
Alcohol-induced mood disorders
Alcohol is a central nervous system depressant. Taken regularly in high doses it may provoke feelings of sadness. Episodes of with-drawal or relative withdrawal can lead to excitability and nervous-ness, including anxiety. The more a person drinks, the more likely it is that these symptoms will occur. Finally in the stage of alcohol dependence, up to 80 per cent of people report depressive symp-toms at some time in their life. About one-third of male patients and up to 50 per cent of female patients have experienced longer periods of severe depression.

(4) These high prevalence rates 
are noteworthy, since more than 20 per cent of alcoholics have attempted suicide once or more and about 15 per cent die in their attempt. Besides depressive features, alcohol-induced mooddisorders may also comprise manic symptoms or mixed features. However, the diagnosis should only be used when the symptoms cause clinically significant impairment or distress in social,occupational, or other areas of functioning.
Concerning treatment, it is interesting to note that despite the 
vast majority of patients who present with depressive symptoms at the beginning of treatment for alcoholism, only very few need specific antidepressant medication or specific psychotherapy. In most other cases depressive symptoms disappear within weeks of controlled abstinence.
(5)
Alcohol-induced anxiety disorders

(5)
This diagnosis should only be used when anxiety symptoms are thought to be related to the direct physiological effects of alcohol. The symptomatology may involve anxiety, panic attacks, 
and phobias. Both alcohol-induced anxiety disorders and mood disorders can develop during intoxication, withdrawal, or up to 4 weeks after cessation of alcohol consumption. During intoxica-
tion or withdrawal, the diagnosis should only be given when the symptomatology clearly exceeds what would be expected from anxiety or depressive symptoms during a regular intoxication or withdrawal episode.
Anxiety disorders are among the most common groups of 
psychiatric disorders in the general population, with prevalence 
rates of up to 25 per cent.
(6) In clinical studies between 20 and 
70 per cent of patients with alcoholism also suffer from anxiety 
disorders.(7) On the other hand, between 20 and 45 per cent of

disorders.(7) On the other hand, between 20 and 45 per cent of 
patients with anxiety disorders also have histories of alcoholism.(8)
However, it has been argued that the comorbidity ﬁ  gures are over-
estimated, because in some of the studies the focus was on drinking 
patterns rather than on alcohol dependence or they describe anxi-
ety symptoms rather than disorders according to diagnostic crite-ria.
(9) Family studies analysing the comorbidity of alcoholism and 
anxiety disorders might be a means of clarifying this controversy. For instance, in the Y ale study the presence of anxiety disorders in the probands slightly increased the risk for alcohol dependence in their relatives, whereas alcohol dependence in the proband did not increase their relative’s risk for anxiety disorders.
(10) Similarly,

(10) Similarly, 
Maier et al .(11) demonstrated an increased risk of alcoholism in probands with panic disorders, but not the reverse. Kendler et al.(12)
in a study of female twins, found evidence that common genetic 
factors may underlie both alcoholism and panic disorder.
Effects on the brain
Cerebral cortex
Chronic alcohol consumption leads to structural and functional changes in the brain. Alcoholic dementia is dealt with in Chapter 4.1.11. Most of the tissue loss from the cerebral hemispheres in alcoholics is accounted for by a reduction in the volume of the cerebral white matter, additionally there is a slight reduction in the volume of the cerebral cortex. This has been demonstrated both pathologically
(13) and using magnetic resonance imaging with 
quantitative morphometry.(14)
Harper et al.(15) documented neuronal loss in alcoholics. There

Harper et al.(15) documented neuronal loss in alcoholics. There 
was a 22 per cent reduction in the number of neurones in thesuperior frontal cortex (Brodmann’s area 8), while survivingneurones showed shrinkage in the superior frontal, motor, and frontal cingulate cortices.
(16) This ﬁ  nding of cortical damage in 
alcoholics is consistent with neuroradiological studies.(14)
Ferrer et al.(17) examined the dendritic tree of cortical neurones 
in alcoholic subjects using Golgi-apparatus impregnation tech-niques. They described a signiﬁ  cant reduction in the basal dendritic 
tree of layer III pyramidal neurones in both the superior frontal and motor cortices. These studies suggest that, even though there is no signiﬁ  cant reduction in the numbers of cortical neurones in the 
motor cortex, there are cellular structural abnormalities that could have important functional implications.
Wernicke’s encephalopathy

The best-known features of heavy alcohol consumption in adults are Wernicke’s encephalopathy and Korsakoff’s syndrome. Wernicke’s encephalopathy is directly caused by thiamine deﬁ  ciency, 
which results from a combination of inadequate dietary intake, 
reduced gastrointestinal absorption, decreased hepatic storage, and 
impaired utilization. Only a subset of thiamine-deﬁ  cient alcoholics 
develop Wernicke’s encephalopathy, perhaps because they have 
inherited or acquired abnormalities of the thiamine-dependent 
enzyme transketolase, which reduces its afﬁ  nity for thiamine.

enzyme transketolase, which reduces its afﬁ  nity for thiamine. 
Wernicke’s encephalopathy is characterized by degenerative changes, including gliosis and small haemorrhages in structures surround-ing the third ventricle and aqueduct: namely, the mammillary bodies, hypothalamus, mediodorsal thalamic nucleus, colliculi, and midbrain tegmentum. Clinical features associated with the Wernicke–Korsakoff syndrome include memory deﬁ  cits, ocular 
signs, ataxia, and global confusional states. Most can be related to damaged functional systems in the hypothalamus, midbrain, and cerebellum. In a large Scandinavian neuropathological study, 12.5 per cent of all alcoholics exhibited signs of Wernicke’s encephalopathy.
(18)
Korsakoff’s syndrome

(18)
About 80 per cent of alcoholic patients recovering from Wernicke’s encephalopathy develop Korsakoff’s amnesic syndrome. It is characterized by marked deﬁ  cits in anterograde and retrograde 
memory, apathy, an intact sensorium, and relative preservationof other intellectual abilities. Korsakoff’s amnesic syndromemay also appear without an antecedent episode of Wernicke’s

445
encephalopathy. Acute lesions may be superimposed on chronic 
lesions, suggesting that subclinical episodes of Wernicke’s encepha-lopathy may culminate in Korsakoff’s amnesic syndrome. The memory disorder correlates best with the presence of histopatho-logical lesions in the dorsomedial thalamus. (Amnesic syndrome is considered further in Chapter 4.1.12.)
Cerebellar degeneration
Many alcoholic patients develop a chronic cerebellar syndrome related to the degeneration of Purkinje cells in the cerebellar cortex. Quantitative studies revealed a signiﬁ  cant loss of cerebellar Purkinje 
cells (by 10–35 per cent) and shrinkage of the cerebellar vermal, molecular, and granular cell layers.
(19) Evidence for a direct toxic 
effect caused by ethanol is provided by animal models.(20)
In neuroimaging studies, however, cerebellar ataxia in alcoholics does not correlate with the daily, annual, or lifetime consumption of ethanol. As in Wernicke’s encephalopathy, thiamine deﬁ  ciency

In neuroimaging studies, however, cerebellar ataxia in alcoholics does not correlate with the daily, annual, or lifetime consumption of ethanol. As in Wernicke’s encephalopathy, thiamine deﬁ  ciency 
due to poor nutrition has also been implicated. Cerebellar atrophy has been reported to occur in about 40 per cent of chronic alcoholics.
(19) In a clinical study of alcoholic inpatients, 49 per cent 
had at least discrete clinical signs of cerebellar atrophy.(21)
The diagnosis of alcoholic cerebellar ataxia is based on the 
clinical history and neurological examination. The ataxia affects the gait most severely. Limb ataxia and dysarthria occur more often than in Wernicke’s encephalopathy, whereas nystagmus is rare. Computed tomography or magnetic resonance imaging scans may show cerebellar cortical atrophy, but a considerable number of alcoholic patients with this ﬁ  nding are not ataxic on examination. Whether

these represent subclinical cases in which symptoms will develop subsequently is unclear. It is interesting to note that impaired cerebellar function improves significantly when abstinence is maintained.
(22)
Hepatocerebral degeneration
Hepatic encephalopathy develops in many alcoholics with liver 
disease, and is characterized by altered sensorium, frontal release signs, ‘metabolic’ ﬂ  apping tremor, hyperreﬂ  exia, extensor plantar 
responses, and occasional seizures. Whereas some patients progress from stupor to coma and then death, others recover and suffer recurrent episodes. The brains of patients with hepatic encepha-lopathy show enlargement and proliferation of protoplasmic astrocytes in the basal ganglia, thalamus, red nucleus, pons, and cerebellum, in the absence of neuronal loss or other glial changes.
(23)
Patients who do not recover fully after an episode of hepatic 
encephalopathy go on to develop a progressive syndrome of

(23)
encephalopathy go on to develop a progressive syndrome of 
tremor, choreoathetosis, dysarthria, gait ataxia, and dementia. 
Hepatocerebral degeneration may progress in a stepwise fashion, with incomplete recovery after each episode of hepatic encepha-lopathy, or slowly and inexorably, without a discrete episode of 
encephalopathy.
Rare disorders
The Marchiafava–Bignami syndrome  is a disorder of demyelin-
ation or necrosis of the corpus callosum and adjacent subcortical white matter. The course may be acute, subacute, or chronic, and is marked by dementia, spasticity, dysarthria, and an inability to walk. Patients may lapse into coma and die, survive for many years in a demential condition, or occasionally recover.Central pontine myelinolysis  is a disorder of the cerebral white

matter that usually affects alcoholics, but it also occurs innon-alcoholics with liver disease including Wilson’s disease,malnutrition, anorexia, burns, cancer, Addison’s disease, andsevere electrolyte disorders such as thiazide-induced hyponatrae-mia; however, the majority of cases occur in alcoholics, suggesting that alcoholism may contribute to the genesis of central pontine myelinolysis in, as yet, undeﬁ  ned ways.
(23) Myelinolytic lesions can 
be reduced experimentally by rapid correction of chronic hypona-traemia. Symptoms include loss of pain sensation in the limbs,bulbar palsy, quadriplegia, disordered eye movements, vomiting, confusion, and coma.
Reversibility of brain damage
Alcohol-related neuroanatomical brain changes have been shown to be partially reversible. These ﬁ  ndings created an ongoing debate 
on possible mechanisms and clinical correlates.
(22)
Foetal alcohol syndrome
The ﬁ  rst description of the foetal alcohol syndrome was given by

(22)
The ﬁ  rst description of the foetal alcohol syndrome was given by 
French scientists in 1968.(24) As a research paradigm, it has a major 
impact on our understanding of alcohol’s effects on the brain. Clinically the syndrome is characterized by: growth retardation involving height, weight, and head circumference; deﬁ  cient intel-
lectual and social performance and muscular coordination; minor structural anomalies of the face, together with more variable involvement of the limbs and the heart.
The basis of this pathology is a cascade of effects exerted
by alcohol on the developing cell. Under normal conditions growth factors enhance the growth of cells and their differen-tiation, but alcohol can diminish these effects.
(25) A second way 
of damaging the developing nerve cell is through the production of free radicals that allow calcium to accumulate in thecells.

(26) The induction of  a free-radical formation is induced
by alcohol. The result of both pathogenic processes is adecrease in the overall size of the brain and a diminution inthe thickness of the outer layers of the cortex, due to decreasesin the total numbers of cells. Impaired nerve cell migrationmight also play a role in the development of the foetal alcohol syndrome.
(27)
The effects of alcohol on the developing brain are clinically 
measured by assessing the head circumference, with a clear dose-
dependent effect.
The foetal alcohol syndrome is considered further in 
Chapter 9.2.7.
Effects on the body
Malnutrition and vitamin deﬁ  ciency
Malnutrition can be a consequence of deficient food intake.

More important in alcoholics seem to be maldigestion andmalabsorbtion (‘secondary malnutrition’). Apart from the direct toxic effect of alcohol on most body tissues, malnutrition isan important contributor to organ damage in alcoholics.
(28)
Vitamin metabolism may be profoundly affected by chronic alcohol consumption. As a consequence, many alcoholics havedeﬁ ciencies in vitamins B1 (thiamine), A, D, B6, and E, and folate. 
This can lead to a variety of physical consequences, includingdamage to different organs.4.2.2.3 alcohol and psychiatric and physical disorders

SECTION 4  clinical syndromes of adult psychiatry 446
Peripheral neuropathy
Besides its effect on the central nervous system, alcohol also dam-
ages motor, sensory, and autonomic nerves that control muscles and internal organs. Symptoms are weakness, numbness, pain, and a prickly feeling or burning of the skin, especially the feet. Usually on neurological examination, the tendon reﬂ  exes are diminished 
or have completely disappeared and skin sensibility is reduced, especially in the feet and in the lower limbs. When patients abstain from alcohol, the progression of the symptoms can be stopped and even partial recovery is possible.
Muscle
Alcohol is toxic to skeletal muscles in a dose-dependent way. Alcoholics often suffer from malnutrition, which adds to the chronic changes in muscles. Chronic myopathy can be found in 40 to 60 per cent of alcohol-dependent patients.
(29) Pathophysiological

(29) Pathophysiological 
mechanisms of muscle damage include alterations in membrane ﬂ uidity, ion channels, and pumps, as well as protein synthesis and 
hormonal dysfunction. Patients complain of pain and weakness. Swelling of the muscle can be easily detected. In chronic states, muscle atrophy is evident. There is no acute treatment for alcoholic myopathy other than abstinence, when acute myopathy can rapidly disappear; chronic myopathy usually only improves, leaving persis-tent weaknesses.
Liver
The effects of ethanol on the liver are among the ﬁ  rst and best-
known symptoms of alcoholism. The ﬁ  rst manifestatio n of alcoholic
liver diseases is the fatty liver. It is followed by early ﬁ  brosis, which 
can be associated with alcoholic hepatitis. If the process continues, irreversible damage leading to severe ﬁ  brosis and to cirrhosis is 
observed.
(30) These effects occur through heavy alcohol consump-
tion even in the absence of dietary deﬁ  ciencies.

observed.
Mortality from liver cirrhosis has long been an important corre-
late of the per capita consumption in a given population. Liver damage is also important because it produces an increase in liver enzymes such as aspartate transaminase, alanine transaminase, and γ-glutamyl transferase, which again are of great practical value as 
diagnostic markers of severe alcohol consumption. Alcohol accounts for more than 80 per cent of all cirrhosis deaths, a conse-quence that seems to be even more pronounced in women.
(31)
Pancreas
About 5 per cent of alcoholics develop chronic pancreatitis. Ethanol seems to damage the pancreas slowly. In general, it takes between 10 and 15 years of heavy drinking before pancreatitis becomes clinically apparent. In the presomatic phase certain changes such as ﬁ brosis, calcium deposits, and especially loss of functioning in

enzyme- and hormone-producing cells can be demonstrated. The acute symptoms are abdominal pain and vomiting. Chronic complications include weight loss, steatorrhoea, and diabetes mellitus.
(32)
Skin
Originally it was believed that skin alterations in alcoholics are due to alcoholic liver disease. However, more recent research has revealed that the skin may be affected much earlier by alcohol misuse.
(33) Whereas the palmar erythema and spider naevi are well-known consequences of alcoholic liver disease, which also 
serve as diagnostic markers for alcoholism, psoriasis and facial ery-thema have less often been linked with high alcohol consumption. Alcohol clearly has to be on the list of agents known to exacerbate psoriasis. One possible mechanism of the action of alcohol on the skin could be a defect in the immune system.
Heart

Heart
Cardiac myopathy is one of the oldest known physical consequences of high alcohol consumption. Similar to ethanol’s effects on skeletal muscles, the cells of the heart muscle are damaged by ethanol’s inﬂ  uence on ion channels and pumps etc. Atrophy leads 
to a dilatation of the heart as a whole.
Recently, the effect of alcohol on coronary heart disease has been 
widely discussed. Indeed, it seems that there is a beneﬁ  cial effect of 
moderate alcohol consumption. Although the reasons are currently under discussion, recent data suggest, that the combination of several actions including changes in lipid metabolism, antioxidant effects, changes in haemostasis and platelet aggregation, arterial vasodilatation mediated by NO release and the expression of cardioprotective proteins contribute to these ‘French Paradox’ .
(34)

(34)
It seems that an alcohol-induced increase in high-density lipopro-teins and a decrease in low density lipoproteins may play a role in this process—an alteration in platelet aggregation could be one possible mechanism of action. Besides cardiomyopathy, cardiac arrhythmias are prominent consequences of alcohol consumption. Close to one-third of all cardiomyopathies can be attributed to alcohol consumption.
Hypertension
A dose-response relationship between drinking and diastolicand systolic blood pressure has been shown consistently.
(31)
In alcohol consuming population, the amount of alcohol con-sumption is significantly associated with hypertension andcardiovascular as well as all cause mortality. It is not clear,however, whether this relationship can only be seen above athreshold level of consumption.
Cancer

Cancer
There is very clear evidence that alcohol increases the risk ofcancer at the upper bronchodigestive tract. This includes cancerof the mouth, pharynx, larynx, and oesophagus. Additionally,alcohol consumption correlates with primary liver cancer. Apossible link between alcohol and breast cancer is still a matterof debate: the association is not strong and not necessarily causative, at least for moderate consumption.
(35) The same seems 
to be true for the correlation between beer drinking and cancerof the rectum.
Schuckit, M.A. (2006). Drug and alcohol abuse: a clinical guide to diagnosis 
and treatment . Springer, Berlin.
Erickson, C. (2007). The science of addiction. From neurobiology to treatment .
W.W. Norton & Company, New Y ork.
Icon Health Publications. (2004). Alcohol addiction—a medical dictionary, 
bibliography, and annotated research guide to internet references . Icon 
Group International, San Diego.

Spanagel, R. and Mann, K. (2005). Drugs for relapse prevention of alcoholism .
Birkhäuser Verlag, Berlin.

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4.2.2.4 Treatment of alcohol dependence
A chronic relapsing disorder

Some people repeatedly put themselves or others at risk by drink-
ing. One view is that such people could drink sensibly if they were more considerate and used more will power. Another increasingly accepted view is that many such individuals are in a state, existing in degrees of severity, in which the freedom to decide whether to change their drinking, and to adhere to that decision, is reduced compared with other drinkers. This state partly depends on per-ceived pay-offs for changing, and on acquired dispositions, which are less accessible to conscious control. Such persons become aware of a wish, or urge, to drink, which overcomes rational thought. They may then make up an explanation, for example, ‘No wonder I feel like a drink, I’ve had a hard day’ .

Such individuals beneﬁ  t from help to unlearn those patterns, 
and to learn different approaches to problems. Discussion, care, 
and encouragement from others can bolster their will to do so. 
Assistance to set-up controls within or from outside themselves may help. Some people can do this without external help, and others with the help of Alcoholics Anonymous ( AA) alone.
(1)4.2.2.4 treatment of alcohol dependence

SECTION 4  clinical syndromes of adult psychiatry 448
This approach argues that dependence on alcohol should be 
managed like other relapsing disorders, such as diabetes and asthma,
(2) by using long-term monitoring coupled with intermit-
tent or continuous treatment.
Starting treatment
The initial interview
Assessment is the ﬁ  rst step of intervention; clumsy interviewing 
alienates an ambivalent patient. The key to success is accepting that the patient is probably in two minds about the interview and about changing his or her drinking habits. Avoid confrontation. The drinking has probably already shown its resistance to deterrence by fear or pain. Gently nudge the matrix of conﬂ  icting motivations in 
the direction of action.
Patients may or may not have been referred for help with alcohol 
problems. Even if they have, the interview should begin withenquiry into the patient’s current concerns. Reﬂ  ective listening
(3)

(3)
helps the patient to clarify these concerns, conveys empathy, and 
avoids premature closure. A spirit of collaborative enquiry helps patients to reach their own conclusions about the role of alcohol
in their troubles. This will be more convincing than a recitationof medical advice. People are more likely to believe what theyhear themselves say than what others tell them. The interviewis less likely to slip into confrontation if the doctor conveysrecognition that, for the patient, drinking alcohol has been pleasur-able. Therefore the assessment should not proceed in a series of closed questions, such as: ‘Do you drink more than you intend to?’ 
‘Does alcohol make you depressed?’ Instead, ask open-ended
questions: ‘T ell me about your pattern of drinking. What are the

questions: ‘T ell me about your pattern of drinking. What are the 
good aspects . . . and what are the disadvantages?’ ‘How does alco-
hol ﬁ  t in with these periods of hopelessness you describe?’ The 
patient may want it understood that at times alcohol has dulled pain. Only then will there be a concession that the cumulative effect 
has been to worsen mood.
A comment such as ‘I’m just a heavy social drinker, not an 
alcoholic’ is not a gauntlet to be seized—an argument about deﬁ  ni-
tions will distract from the work of clarifying and planning how to deal with the current problems. Instead, a response such as ‘I gather you don’t like labels’ may reveal pertinent fears and prejudices (e.g. that alcoholics are failures, who get locked up in hospital).
Denial permits dismissal of unpleasant or unwanted facts and

Denial permits dismissal of unpleasant or unwanted facts and 
feelings. It hurts to admit that you have lost your family’s respect, or that you will have to give up alcohol, which you enjoy. Alcohol problems still carry disgrace. In Islamic cultures, where alcohol is forbidden, denial from shame may be deepened by fear of punish-
ment from the authorities.
Explain symptoms
Help the patient to understand withdrawal symptoms and how 
they can abort attempts to reduce consumption. Patients frequently attribute withdrawal symptoms to other causes; for example, wak-ing at 4 a.m. with sweats and anxiety may be attributed to worry, and trembling hands in the morning to stress.
Informant
If the partner, a close friend, or a relative is present from the start, the salient points usually emerge more rapidly. However, the patient should also be seen alone because matters to do with the police, an employer, the bank, or a lover may still be unknown to the partner.

Relatives should hear the exchange between doctor and patient, otherwise the version they hear later from the patient may be diluted: ‘The doctor says I’m not an alcoholic’ . This can leave relatives even angrier than before, convinced that no one under-stands their distress and that the drinker has once again deceived the doctor.
Assessments
The use of a breathalyser or saliva test to measure blood alcohol concentration puts alcohol consumption ﬁ  rmly into the objective 
arena. Use the test before the individual starts to detail recent drinking, there is nothing to be gained from showing that the patient sometimes minimizes the drinking.
Physical signs may be helpful. Heavy drinking may cause 
excessive capillarization in the conjunctivae or in the skin of the nose and cheeks. The liver may be enlarged. Look for tremor in the outstretched tongue, which is less commonly concealed (or exag-gerated) than tremor in the ﬁ  ngers. Tachycardia is another useful

sign of withdrawal. In a hyperaroused fearful patient, who has already been without a drink for 24 h, a pulse of over 110 beats/min may presage delirium tremens.
Clinicians vary in how structured an assessment they prefer, but 
at some point in the ﬁ  rst one or two interviews the following should 
be noted: drinking patterns, history of withdrawal symptoms, previous attempts to stop drinking, use of drugs (prescribed and 
not prescribed), physical complications including head injuries, police, or Court involvement (past and current), dwelling arrange-ments, problems at home, trouble at work (specifying whether the employer has commented on drinking alcohol and/or started disciplinary action), psychiatric illness, family history, previous treatments, and experience of AA.
Medical assistance for withdrawal
Medical assistance to reduce the short-term discomfort of with-drawal can be the beginning of restructuring of thoughts and lifestyle towards long-term abstinence.

If dependence is severe, especially in an unplanned situation 
where a very heavy drinker is suddenly deprived of alcohol because of an accident, illness, or police arrest, care must be taken to pre-vent the life-threatening complications of convulsions or delirium. Anticipation is the key.
When dependence is less marked, withdrawal symptoms are mild 
and the person can stop drinking by gradual reduction, encour-aged by the physician or a friend.
When the patient’s aim is ‘controlled drinking’(see below), this 
may also entail an initial stage of withdrawal, as the ﬁ  nal goal is 
more likely to be achieved after abstinence for 2 or 3 months.
The setting
Controlled studies have shown that outpatient withdrawal is safe and effective for mild and moderately dependent alcoholics.
(4,5)

(4,5)
Advice for patients withdrawing at home is given in Box 4.2.2.4.1. Hayashida et al .
(4) randomly allocated 164 mild to moderately 
affected patients to either inpatient or outpatient detoxiﬁ  cation. 
Completion was successful in 95 per cent of the former and 72 per cent of the latter; inpatient care cost eight times more than outpatient care.

449
Admission to a hospital is indicated when the home social milieu 
is inimical to abstinence, or when there is a history of withdrawal convulsions or delirium; it is urgent when there are any signs of Wernicke’s encephalopathy.
A benzodiazepine(6) is prescribed for two reasons: ﬁ  rst, to reduce 
the risk of severe withdrawal symptoms with delirium or convul-sions (indicated if recent consumption has been more than15 units/day for more than 10 days); second, to assist theindividual whose wish to abstain or reduce drinking is overcome by longing for alcohol (craving), shaking, anxiety, insomnia, or nausea and vomiting.
A typical outpatient regimen would be chlordiazepoxide 20 to

A typical outpatient regimen would be chlordiazepoxide 20 to 
30 mg four times daily, reducing to zero over 5 days, with the larger doses given at night (Table 4.2.2.4.1). Medication is issued on the understanding that the patient does not also take alcohol. If there is any doubt that this instruction will be followed, medication is issued daily and a check made (ideally by breath or saliva tests) that drinking has not been resumed. Chlordiazepoxide is preferred to 
diazepam for outpatient use because it has a lower street value and 
is therefore less likely to be sold on. When managing severe with-drawal symptoms with marked agitation and tremor, or incipient delirium, diazepam (starting at 10 mg four times daily) is preferred because it has a more rapid action and can be given parenterally. 
A benzodiazepine with one metabolite only and a shorter half-life (e.g. oxazepam, lorazepam) is preferred if liver function is signiﬁ  -

cantly impaired (i.e. there is jaundice, ascites, oedema, low serum albumin, or raised serum bilirubin).
For inpatients, a benzodiazepine such as diazepam 10 mg may be 
given every hour until symptoms are controlled (symptom-triggered dosing). This procedure leads to lower total prescription of benzodiazepine, less oversedation, and quicker discharge from hospital.
(7)
If the patient is vomiting, give metoclopropamide 10 mg
intramuscularly 30 min before the first benzodiazepine tabletand/or perhaps choose a benzodiazepine that can be administered parenterally; lorazepam 1 mg is absorbed adequately from theintramuscular site, or diazepam 10 mg can be given intravenously (or rectally).
Treating convulsions
With the aim of preventing further convulsions, the patient who has just had a ﬁ  t or is in a ﬁ  t is given 10 mg diazepam. Consider giv-

ing 15 to 20 mg in a patient who has been taking benzodiazepines regularly prior to this event, or is much above average weight. It is illogical to commence an anticonvulsant, which may take 2 to 3 days to reach a therapeutic serum level. Rather, increase the dose of the benzodiazepines. A convulsion may presage delirium.
Preventing convulsions
Deaths have occurred in hospital, prison, and police cells from repeated alcohol withdrawal ﬁ  ts. When withdrawal is planned in 
patients with a history of ﬁ  ts of any cause the risk can be reduced 
by commencing phenytoin (300 mg daily) 4 days before the cessa-tion of drinking. In an acute situation, larger than normal doses of long-acting benzodiazepines are given in the ﬁ  rst 36 h without

by commencing phenytoin (300 mg daily) 4 days before the cessa-tion of drinking. In an acute situation, larger than normal doses of long-acting benzodiazepines are given in the ﬁ  rst 36 h without 
waiting until the blood alcohol level has fallen to zero. The benzo-diazepine should be started as soon as the blood alcohol level can be presumed to be falling, even though the patient still smells of alcohol or has a positive breath test, provided that he or she is sober enough to understand and cooperate with the procedure.
Treating delirium tremens
Increasing the dose of the benzodiazepine may be sufﬁ  cient to

control the agitation. If not, the slight epileptogenic effect of anti-psychotic drugs should not deter their use, especially if delusions and hallucinations have developed, provided that anticonvulsant protection by a benzodiazepine is in place. Parenteral haloperidol plus parenteral lorazepam is usually effective. When a patient’s Box 4.2.2.4.1  Advice to patient on withdrawing from alcohol at 
home
If you have been chemically dependent on alcohol, stopping 
drinking causes you to become tense, edgy, perhaps shaky or sweaty, and unable to sleep. There can be vomiting or diarrhoea. This ‘rebound’ of the nervous system can be severe. Medication controls the symptoms while the body adjusts to being without alcohol. This usually takes 3 to 7 days from the time of your last alcoholic drink. If you did not take medication, the symptoms would be worst in the ﬁ  rst 48 h, and then gradually disappear.

This is why the dose starts high and then reduces.
Y ou have agreed not to drink alcohol . Y ou may become thirsty. 
Drink fruit juices and water but do not overdo it. Y ou do not have to ‘ﬂ  ush’ alcohol out of the body. More than 3l of ﬂ  uid could 
be too much. Do not drink more than three cups of coffee or ﬁ  ve 
cups of tea. These contain caffeine, which disturbs sleep and causes nervousness.
Aim to avoid stress . The important task is not to give in to 
the urge to take alcohol. Help yourself relax by going for a walk, listening to music, or taking a bath.
Sleep . Y ou may ﬁ  nd that even people with capsules, or as they 
are reduced, your sleep is disturbed. Y ou need not worry about

are reduced, your sleep is disturbed. Y ou need not worry about 
this lack of sleep as it does not seriously harm you, but starting to drink again does. Y our sleep pattern will return to normal in a month or so. It is better not to take sleeping pills so that your natural sleep rhythm returns. Try going to bed later. Take a bed-time snack or milky drink. The capsules may make you drowsy so you must not drive or operate machinery. If you become drowsy, miss out a dose.
Meals . Even when you are not hungry, try to eat something. 
Y our appetite will return.Table  4.2.2.4.1  Example of a ﬁ  xed-dose regime for outpatient 
alcohol withdrawal using capsules of chlordiazepoxide 10 mg
First thing 12 noon 6 p.m. Bedtime
Day 1 3 3 3
Day 2 2 2 2 3
Day 3 2 1 1 2
Day 4 1 1 2Day 5 1 14.2.2.4 treatment of alcohol dependence

SECTION 4  clinical syndromes of adult psychiatry 450
behaviour is uncontrolled or dangerous, transfer to a secure unit 
may be needed. Authoritative calm nursing reduces the risk of aggression. Hospitals should have an emergency team of sufﬁ  cient 
personnel to manage disturbed patients.
Preventing delirium tremens
If confusion and hallucinations develop, this usually occurs 48 to 72 h after the last drink. Sufﬁ  cient benzodiazepine, given early in 
the withdrawal, reduces the risk, as does sensitive nursing in a quiet evenly-lit environment. Explaining symptoms and orientating the patient reduces anxiety, paranoia, and confusion.
Vitamin therapy
It is reasonable to prescribe thiamine 50 mg orally three times a day for 2 to 3 weeks, as thiamine stores may be depleted because of poor diet and alcohol-impaired gut absorption. Wernicke–Korsakoff syndrome is life-threatening and steps must be taken to avoid it developing.
(8) The malnourished patient, or the patient

(8) The malnourished patient, or the patient 
who shows any sign of Wernicke’s encephalopathy (confusion, ataxia, ophthalmoplegia, nystagmus—do not wait for the ‘triad’ of symptoms), must be given immediate parenteral B vitamins. Anaphylactic shock was a very rare complication of some older preparations. It is less likely with intramuscular than intravenous injection; infusion saline drip, when practicable, is probably prefer-able to slow bolus injection.
Interventions to reduce relapse
The evidence
With appropriate help, withdrawing from alcohol is not the dependent drinker’s main difﬁ  culty. The main difﬁ  culty is avoiding 
relapse into further problematic drinking or dependence.
Before the era of randomized controlled trials, psychiatrists 
typically would explore with patients possible personality or psychological causes of their excessive drinking—trying to ﬁ  nd out

typically would explore with patients possible personality or psychological causes of their excessive drinking—trying to ﬁ  nd out 
‘why?’ . However, evidence that this reduced relapse was lacking. Indeed, it may have sometimes had an adverse effect by reinforcing the drinkers’ perception of having a need to drink and by creating transference problems which might later trigger drinking.
(9) Non-
directive counselling may also sometimes have had negative effects, acting as a confessional, with a sense of absolution allowing further drinking.
In recent years, several systematic reviews and meta-analyses 
have been conducted of treatments to prevent relapse in alcohol dependence. Drawing on data from high quality trials a consensus has emerged.
(10–12)  Effective treatment are social skills training 
based on behavioural cognitive therapy principles,(13) motivational

based on behavioural cognitive therapy principles,(13) motivational 
enhancement(14) albeit tested sometimes in less severe groups of 
patients, the community reinforcement approach,(15) behaviour 
contracting, and behavioural marital therapy(16) and the pharma-
cotherapies described below.
Abstinence or ‘controlled drinking’?
Harmful or hazardous use of alcohol without severe dependence can sometimes revert to risk-free drinking. Patients with social supports (family and job) and without impulsive personalitiesand many social problems are most likely to succeed. For others, including most of those dependent on alcohol, the goal of absti-nence is better.
(29) Among patients attending specialized clinics,the proportion who can sustain problem-free drinking for at least 
1 year is small—5 per cent is a typical ﬁ  nding.(17–19) A randomized

1 year is small—5 per cent is a typical ﬁ  nding.(17–19) A randomized 
trial comparing the goals of controlled drinking and abstinence did not favour controlled drinking.
(20) However, for patients without 
established dependence, reduction programmes (whether or not towards abstinence) using FRAMES (Table 4.2.2.4.2) proved to be more effective than no intervention.
(21–23)  Interventions in primary 
care are discussed in Chapter 4.2.2.5.
If controlled drinking is the agreed goal, the patient and
physician collaborate to monitor the amount and pattern of the drinking as follows:
1 Limit number of days of drinking and number of drinks on any 
occasion.
2 Slow the rate of drinking, and/or reduce alcoholic strength of 
drinks.
3 Develop assertiveness skills for refusing drinks.
4 Design reward system when goals are achieved.

occasion.
drinks.
5 Develop awareness of triggers to overdrinking.6 Practise other ways of coping with triggers.7 Record pattern and amount of drinking, for example in a diary.8 Physician and patient monitor γ-glutamyl transferase blood test 
results.
Maintaining motivation and compliance
Enhancing motivation has a place not only at onset, but through-out the clinical contact. Treatment aimed only at enhancing motivation was for most outcome measures equal to cognitive behavioural therapy, and intensive intervention aimed at linking patients with AA.
(24) Randomized controlled studies have shown 
the advantage of motivational interviewing over traditional sup-portive therapy.
(10–12,25) The style of the opening interview using

(10–12,25) The style of the opening interview using 
motivational interviewing techniques has already been discussed. The patient is encouraged not to forget the harm that drinking caused and the beneﬁ  ts of abstinence, but the losses and problems 
of being sober are not denied. Strategies for maintaining abstinence emerge from collaborative dialogue, and are owned by patients rather than offered as advice from the clinician. If medication is part of the treatment plan, unwanted effects are actively enquired into, and are recognized and not dismissed, and remedies are sought. Any discrepancies that patients reveal between their pres-ent view of themselves and how they would like to be, or between what patients say they believe and how they actually behave, are Table  4.2.2.4.2  FRAMES: ingredients of a brief intervention

Feedback about personal risk or impairment
Responsibility: emphasis on personal responsibility for change
Advice to cut down or, if indicated because of severe dependence or harm, 
 to abstain
Menu of alternative options for changing drinking pattern
Empathic interviewing
Self-efﬁ  cacy: an interviewing style which enhances this
Reproduced with permission from T.H. Bein, et al.  (1993), Motivational interviewing with 
alcoholic outpatients, Behavioural and Cognitive Psychotherapy , 21, 347–56, copyright 
1993, with permission from Cambridge University Press.

451
used as a fulcrum for shifting attitudes and testing alternative 
strategies. These techniques were elaborated by Miller and 
Rollnick(3) and enshrined as motivational enhancement therapy(26)
by Project MATCH (see below).
Helping motivation: the social matrix
It is said that the only successful way to change your drinking is ‘to 
do it for yourself’ . Nevertheless, many of those dependent on alcohol 
start on the road to recovery because of pressure from outside. For 
example, if the person ﬁ  nds himself in Court, or has lost his driving 
licence, authorities may seek evidence that the offender has taken 
steps to alter harmful drinking patterns. Perhaps the partner is now 
being ﬁ  rmer, even demand a separation or divorce; or the employer 
has given a warning.
Friends, partners, colleagues at work, and even employers some-
times adopt an approach that they believe to be motivating but 
which has the opposite effect and enables the drinker to continue

which has the opposite effect and enables the drinker to continue 
drinking. For example, they may cover-up, gloss over, make excuses, 
or even blame themselves for what is going wrong. This cushions 
drinkers from experiencing the harmful consequences of their 
drinking or allows them to believe that alcohol is not the chief 
problem, despite evidence that alcohol is in fact the critical com-
mon factor in their downward spiral.
A physician can help the parties improve communication so that 
important messages are not lost. If the message from the employer 
or partner, or even the children, is clear and positive, it can have a 
powerful motivating effect: ‘We value our relationship with you. 
But the way you are drinking is harming that relationship and we 
will not tolerate it’ .
Some physicians are overcautious about conﬁ  dentiality in this

Some physicians are overcautious about conﬁ  dentiality in this 
situation. If a doctor is asked by a partner or an employer to com-
ment on the patient’s condition, he or she may or may not have 
permission, or feel it appropriate, to do so. But doctors can usefully 
help partners or employers clarify for themselves what they want, 
and then encourage a clear and ﬁ  rm, but positive message.
Sometimes doctors unwittingly collude in a cover-up. The 
smokescreen that can be set-up by a drinker who is severely depen-
dent and ambivalent about change can be hard to penetrate: ‘It’s 
depression, doctor’; ‘It’s stress at work’; ‘If only my wife was more 
understanding/my sleep was not so disturbed/I didn’t get these 
memory blanks which I think are some kind of stroke’ . The doctor 
may need to wait for that medical moment, perhaps a crisis, to help

may need to wait for that medical moment, perhaps a crisis, to help 
such an individual. Or, if the doctor has patience, the drip, drip of 
non-judgemental evidence, and perhaps some social pressure, may 
bring about the necessary change in the patient’s understanding 
and thus the perceived motivational pay-offs. Understanding may 
lead to action. However, as Fig. 4.2.2.4.1 shows, that action may not 
be sustained and the process of helping understanding may need to 
be repeated many times.(27)
There are few randomized controlled studies allocating patients 
to different intensities of external motivation. However, alcoholics 
coerced into treatment have medium-term outcomes similar to 
those who attend voluntarily.(28)
Coping skills therapies
When incentives are powerful, many newly abstinent patients are

When incentives are powerful, many newly abstinent patients are 
able to abstain for short periods. Others lack the skills to cope with 
the triggers to drinking even when their motivation to abstain has 
been strong. Cognitive behavioural therapies seem to improve the coping skills of these patients. If the triggers are in social situations, 
assertiveness, or conversation skills training can help. If the trigger 
is related to relationship of work problems, checking beliefs 
and attitudes, and reframing stressors may reduce the urge to use 
alcohol as a sedative.(13) Some patients are helped by learning to 
handle frustration and criticism without harbouring anger and 
resentments. Treatment can be in groups, where the opportunity to 
discuss these topics with others who have similar problems is 
appreciated. Groups also enable learning through role playing and

appreciated. Groups also enable learning through role playing and 
by modelling on others. ‘Relapse prevention therapy’ as originally 
formulated has not stood up to meta-analytic critique.(11)
Cue exposure
The smell or sight of alcoholic drinks can be a powerful stimulus to 
drinking. Initial studies(30) found that ‘deconditioning’ by exposing 
inpatients to the sight and smell of their preferred drinks in a labora-
tory setting, without drinking, was associated in the coming 6 months 
with a longer period without a relapse. However, this is not a stand-
alone treatment. Patients should not court danger by going into pubs 
and bars—these are places where people go to drink alcohol.
Couples should decide together whether or not to have 
alcohol in the house, but patients should not be encouraged to ‘test 
themselves’ .
Alcoholics Anonymous

There are many ingredients in the healing process of AA. Newcomers 
are helped to identify with others as members tell their stories. 
They see that it is possible to be frank about past errors and the 
hurt caused to others through the drinking. T elling their own story 
helps the members not to forget the harm that accrued from drink-
ing. This reduces complacency, which is one of the most common 
precursors of relapse.
Alcoholism is viewed by AA as a physical, psychological, and 
spiritual illness, which can be arrested (by avoiding another drink) 
but cannot be cured. The meetings offer a new social network. 
Emotional openness is encouraged. Members learn to express 
warmth, and to accept that they and others have failings. The AA 
advice on coping with emotions and relationship difﬁ  culties has

advice on coping with emotions and relationship difﬁ  culties has 
much in common with cognitive behavioural therapy and relapse 
prevention therapy. The method has some attractively simple 
concepts (‘Just don’t pick up that ﬁ  rst drink’; ‘HALT’—being alert 
to four of the most common triggers to relapse, i.e. hunger, anger, 
Fig. 4.2.2.4.1 Wheel of change. (Reproduced from J. Prochaska and C. DiClementi. 
Stages of change in the modiﬁ  cation of problem behaviours. In Progress in behavior 
modiﬁ  cation , Vol. 28 (eds. M. Hersen, R. Eisler, and P . Miller), pp. 183–218, copyright 
1984, Sage Publishing, Sycamore, IL.4.2.2.4 treatment of alcohol dependence

SECTION 4  clinical syndromes of adult psychiatry 452
loneliness, tiredness). There is a deeper aspect, which is to replace 
preoccupation with self by handing over to the group process, or to a ‘Higher Power’ .
Accepting that you are ‘powerless’ to control your drinking is the 
‘ﬁ rst step’ in AA. This entails ceasing the struggle and letting the 
‘Higher Power’ take over. Members vary in their interpretation of the ‘Higher Power’ , and avowed atheists should not be deterred from sampling AA. Residential, outpatient, and day programmes, which teach the AA approach are sometimes called 12-step pro-grammes (Box 4.2.2.4.2). One of their strengths is linking patients to the AA network. In Project MATCH,
(24)
A psychiatrist can introduce patients to AA through a contact

(24)
A psychiatrist can introduce patients to AA through a contact 
member who will tell the patient how AA works, will not ask per-sonal details, and will extend an invitation to a meeting. Doctors are welcome to attend ‘open’ AA meetings to see how it works. A contact number is given in local telephone directories. AA does not work for everyone, but since it is difﬁ  cult to predict who will 
be helped, it is good practice to offer contact to all patients with impaired control of their drinking.
A warning, often based on personal experience, may be given at 
AA meetings about transferring dependence from alcohol to other drugs. This usually refers to use of barbiturates or benzodiazepines, or to the danger of relying on a medication instead of adjusting one’s way of living. The use of prescribed medication is not formally disapproved of by AA.
Evidence of efﬁ  cacy
Naturalistic non-randomized studies have shown that treatment

Naturalistic non-randomized studies have shown that treatment 
programmes using the AA approach are associated with outcomes in drinking and overall functioning similar to those of programmes 
using the cognitive behavioural approach. Patients in 12-step programmes improve on self-efﬁ  cacy and coping skills scores much 
as patients treated by cognitive behavioural therapy.
(31) Following 
the steps of AA is associated with improving drinking and psycho-social outcomes.
(32)
Only two randomized controlled studies of 12-step programmes 
have been conducted. One compared inpatient treatment (with fewer hours of psychotherapy than many such programmes) with a 12-step inpatient programme (with slightly more hours of therapy). There was a non-signiﬁ  cant trend towards a greater total abstinence 
programme and less relapse in the 12-step programme.
(33) In

(33) In 
Project MATCH, patients were randomly allocated to cognitive behavioural therapy, motivational enhancement therapy, or ‘12-step facilitation’ , which instructed patients in the tenets of AA, and assisted and encouraged them to attend AA meetings. The three treatments resulted in similar outcomes after 1 and 3 years. However, for those who had been relatively free of psychiatric problems at entry to the study, 12-step facilitation was associated with slightly better outcomes after 1 year. After 3 years the 12-step facilitation led to better outcome for patients who, at entry to the study, had family, social, or work environments bringing them into frequent contact with drinking.
(34)
Help for the family
The family of someone with a drinking problem may suffer for years without recognition and can beneﬁ  t from advice and under-

(34)
standing. They are a vital monitor of the patient’s progress. Good family cohesion and low expressed emotion predict better out-come, even after controlling for the predictors of demographic variables and severity of alcohol dependence.
Life in the family becomes increasingly restricted. Finances 
dwindle. The children fear that the parent may be drunk, and so stop inviting friends to visit. They dread that arguments between mother and father will become violent. The drinker’s behaviour becomes slovenly. He or she may wet the bed. Despite these hurts, the drinker may still make the family believe that they are thereason he or she drinks.
The invitation to a family member or partner to attend with the 
patient may be rejected if the drinker is the messenger, and the

patient may be rejected if the drinker is the messenger, and the 
message is distorted to: ‘The doctor says you’re part of the problem’ . A direct letter or telephone call from the clinician requesting ‘your views on how I can assist’ reduces the partner’s fear of beingburdened with extra guilt or responsibility.
The clinician can help reduce family behaviours, such as hostility 
or cover-up, that are damaging to the family and counterproductive for the drinker’s recovery. Communication between the drinker and the spouse or children has often broken down. In many coun-tries family groups, such as Al-Anon, provide help to families.
Behavioural marital therapy

When the patient is in a relationship, its quality can be motivating or demotivating. Reciprocal contracts are aimed at making the rela-tionship more rewarding for each partner. Although abstinence is a prerequisite, speciﬁ  c agreements should not be contingent on the 
drinking
(35); otherwise, a relapse means that the partner ceases to 
work on the relationship. Another prerequisite might be that physi-cal violence is excluded. Contracting could start thus: ‘Although you Box 4.2.2.4.2  The 12 steps of Alcoholics Anonymous
 Step 1  We admitted we were powerless over alcohol-that our 
lives had become unmanageable.
 Step 2  Came to believe that a power greater than ourselves 
could restore us to sanity.
 Step 3  Made a decision to turn our will and our lives over to 
the care of God as we understood him .
 Step 4  Made a searching and fearless moral inventory of 
ourselves.
 Step 5  Admitted to God, to ourselves, and to another human

 Step 5  Admitted to God, to ourselves, and to another human 
being the exact nature of our wrongs.
 Step 6  Were entirely ready to have God remove all these defects 
of character.
 Step 7 Humbly asked him to remove our shortcomings.
 Step 8  Made a list of all persons we had harmed, and became 
willing to make amends to them all.
 Step 9  Made direct amends to such people wherever possible, 
except when to do so would injure them or others.
Step 10  Continued to take personal inventory and when we 
were wrong promptly to admit it.
Step 11  Sought through prayer and meditation to improve 
our conscious contact with God as we understood him ,
praying only for knowledge of his will for us and the power to carry that out.
Step 12  Having had a spiritual awakening as a result of these 
steps, we tried to carry this message to practice these principles in our affairs.

453
are responsible for not drinking, is there anything that your
partner could do more of, or less of, that would help you stickto the plan?’ Check that the requests are reasonable and available before the partner is asked to agree. The partner makes reciprocal requests and negotiation follows. Even requests for small changes can start the process.
The partners should give clear messages, owning their state-
ments: ‘This is what I would like’ , ‘It makes me feel good if you . . . ’ . They will need to be reminded to state the positives and to practise being good listeners, giving non-verbal signals that they are listen-ing, and not butting in with unsolicited good advice.
Violence in the partnership may require speciﬁ  c attention. If the

Violence in the partnership may require speciﬁ  c attention. If the 
drinker is intoxicated, the partner is advised to back off and avoid argument. Sometimes each partner is asked to sign an agreement that neither will threaten nor hit the other. If they do, time-out in another room is agreed in advance to permit slow-breathing to aid calming down, or one of them will leave the house and go to a designated place for 36 to 72 h.
When the partner ‘brings up the past’ , this can be a major irritant 
to the drinker. But this can be reframed as the partner ‘helping the couple not repeat their past’: the partner who feels heard and understood is more ready to look at changes that he or she might also make.
Efﬁ cacy
Behavioural marital therapy produces better outcomes of drinking

Efﬁ cacy
Behavioural marital therapy produces better outcomes of drinking 
and marital relations than individual counselling or similar control conditions. The superior effects last for 24 months after treatment. Outcome at 1 year is better if sessions of behavioural marital therapy continue after the end of treatment to reinforce what has been learnt and rehearse relapse prevention plans.
(36)
Deterrent medication
Disulﬁ  ram
If taken in a sufﬁ  cient dose for at least the preceding 3 to 4 days, 
disulﬁ  ram causes an unpleasant reaction to develop 15 to 20 min 
after alcohol enters the body. The reaction is due to accumulation of acetaldehyde, an intermediate metabolite of ethanol. The reac-tion includes ﬂ  ushing, headache, pounding in the chest or head,

after alcohol enters the body. The reaction is due to accumulation of acetaldehyde, an intermediate metabolite of ethanol. The reac-tion includes ﬂ  ushing, headache, pounding in the chest or head, 
tightness in breathing, nausea, and sometimes vomiting. Hypotension can occur and is potentially dangerous. (In some countries, calcium carbimide, which has the same action is also available.) The disulﬁ  ram–ethanol reaction varies in intensity. It is 
recognized practice to increase the dose of disulﬁ  ram up to 400 mg 
daily if the patient has tested the alcohol reaction and it has not been severe enough to act as a deterrent.
Disulﬁ  ram is an aid, not a cure. The individual can become used 
to life without alcohol. This allows time for conﬁ  dence to recover—
in the family, at work, or in the social services if there have been

in the family, at work, or in the social services if there have been 
concerns about the safety of children. Patients may object that it is weakness to take a deterrent, and they prefer to show that they can use will power. Explain to the patient that will power is not always there when most needed. With disulﬁ  ram a decision to drink or 
not still has to be made, but only once a day.
Unwanted effects which occur even when no alcohol is taken 
include drowsiness, bad breath, and headache. These make the drug unacceptable to some patients. Concerns that disulﬁ  ram can harm 
the liver are based on a few case reports (the risk is about 1 in 25 000 patient-years). It appears to be a hypersensitivity reaction, 
and if it is to occur it is likely to be in the ﬁ  rst month. Overall, 
disulﬁ  ram is associated with improved liver function tests com-
pared with control groups, presumably owing to reduction of drinking.

(37) Peripheral neuropathy (almost always reversible) has 
been reported following several months at doses of over 250 mg: the risk maybe greater when the patient takes other drugs suchas antidepressants which are metabolized in the liver. There are a few reports of psychosis induced by disulﬁ  ram, and psychotic
illness has been a formal contraindication in the licensing insome countries. The risk is so low and the need to help schizo-phrenic patients with alcohol problems is sometimes so great that in other countries this contraindication has been changed to a‘caution’ . There are many documented cases where improvement has occurred in psychotic patients while taking disulﬁ  ram, and
in a dose of up to 250 mg daily there are no problems from unwant-ed actions or interactions with medication for the psychiatricillness.
(38)
(a) Efﬁ  cacy

(38)
Disulﬁ  ram will only aid recovery if it is taken regularly in a sufﬁ  -
cient dose to deter. Earlier studies without attempts to increase adherence to the medication did not show efﬁ  cacy unlike studies in 
which enhanced compliance was enhanced by arranging supervi-sion. In some of these studies there was a degree of coercion; for example, if the patient ceased taking the disulﬁ  ram the partner 
might withdraw from some agreed item, or disciplinary action at work might be reinstated.
The disulﬁ  ram effect depends on the patient knowing that they 
have ingested the disulﬁ  ram, and so only single blind studies 
are appropriate to test its efﬁ  cacy. Single blind studies over 1 year 
have shown, in patients with a family member to supervise the medication, that disulﬁ  ram is associated with less relapse than 
acamprosate

(39) and naltrexone.(40)
(b) Suggested mode of use
Before prescribing, a physical examination and baseline liver function tests are performed. The patient is encouraged to ask the partner, a nurse, or welfare ofﬁ  cer at work or at the health centre, or 
a pharmacist to see that the disulﬁ  ram is taken. This can be daily, or 
three times a week, provided that the total weekly dose is sufﬁ  cient, 
i.e. at least 7 × 200 mg. Some specialist clinics have follow-up clinics thrice weekly to supervise disulﬁ  ram. A programme com-
mencing for the ﬁ  rst months with frequent clinic attendance, and 
thereafter encouragement to continue using disulﬁ  ram, reported 
abstinence rates of over 50 per cent in patients followed for up to 7 years.
(41) The product is available in a dispersible form to be taken 
in water so that it can be seen to be swallowed.

There should be medical follow-up, but there is no consensus 
as to whether monitoring of liver function tests should be carried out beyond the first month. However, monthly follow-up isappropriate to check for signs of drinking and of any unwanted effects.
It is common to prescribe disulﬁ  ram for 6 months, but many 
patients ask to continue for longer and there may be slipswhen disulfiram is withdrawn, even after long periods ofabstinence. Some patients keep a supply to use when they feelan increased risk of drinking, for example on a business trip or at a social event.4.2.2.4 treatment of alcohol dependence

SECTION 4  clinical syndromes of adult psychiatry 454
Speciﬁ  c neurotransmitter antagonists
(a) Acamprosate (calcium acetyl homotaurinate)
Acamprosate enhances γ-aminobutyric acid ( GABA ) transmission 
and antagonizes glutamate transmission, probably by antagonizing N-methyl- d-aspartate receptors (see Chapter 6.2.8). It reduces 
drinking in alcohol-dependent animals, and reduces the reinstate-
ment of drinking behaviour in animals re-exposed to alcohol after a period of abstinence. Animals do not seek out acamprosate as they do addictive substances, and it does not have mood-altering or drug-abuse potential in humans.
(42) It has no deterrent or 
disulﬁ  ram-like effect.
Acamprosate is excreted unchanged in the kidney. It has few

Acamprosate is excreted unchanged in the kidney. It has few 
unwanted effects; diarrhoea, and abdominal discomfort are the only ones reported in more than 10 per cent of patients (up to 20 per cent) and these are mild and transient. It does not exacer-bate psychomotor impairment caused by alcohol. There are no known drug interactions. Systematic follow-up after the end of acamprosate treatment shows no sudden relapse and no discon-tinuation symptoms in patients who have received the medication for up to 1 year.
(i) Efﬁ  cacy
Acamprosate has a dose-related effect of improving abstinence rates in recently detoxiﬁ  ed patients. There are no studies compar-
ing the advantages of differing lengths of treatment. Meta-analysis of published studies ﬁ  nds that acamprosate is associated with 
improvement in abstinence rate compared to placebo with an odds ratio of 1:88 and greater cumulative days of abstinence.
(43)

(43)
Acamprosate has only been tested in patients who intend to 
abstain from alcohol. It has not been tested formally in patients aiming for controlled drinking. However, in literature, patients who resume drinking, consume less alcohol in subsequent days
(44)
if they had been allocated to acamprosate than to placebo.
(ii) Suggested mode of use

(44)
Acamprosate is indicated for patients who have withdrawal symp-toms and relief drinking typical of severe alcohol dependence and requiring medical assistance to withdraw. It is started 2 to 7 days after the last drink (steady state pharmacokinetics are reached after 5 days). Patients who relapse while on acamprosate are advised to continue taking the medication and exert effort to limit the lapse. However, acamprosate is not normally continued in patients who relapse more than once despite regularly taking the drug. Those who appear to be beneﬁ  ting from it should continue the drug for at 
least 6 months, and up to 1 year if there has been a history of repeated relapsing while in treatment.
Several studies have shown that acamprosate reduces self-reported

Several studies have shown that acamprosate reduces self-reported 
craving for alcohol. Some newly abstinent patients experience strong craving, but others experience very little and there is no evidence that this should be a criteria for deciding to whom this 
medication should be offered.
Acamprosate may sometimes help prolong abstinence among 
patients who choose to take disulﬁ  ram.
(45)
(b) Opiate antagonists
Endorphins are released in one of ethanol’s many acute actions
on the limbic system. It has been suggested that this effect
contributes to loss of control.(46) Naltrexone (and nalmefene) anta-
gonize the neurotransmitter action of endogenous endorphins.Naltrexone has been shown to reduce ethanol-seeking in alcohol-
dependent animals. It does not exacerbate the psychomotorimpairment caused by alcohol.
Some patients who drink alcohol while taking naltrexone report

Some patients who drink alcohol while taking naltrexone report 
that they feel less of the ethanol ‘high’ . This could lead to less impulse to carry on drinking.
(47,48) However, some studies have 
reported an increase in total abstinence as well as a reduction of drinking overall.
(48,49) It is possible that the reduced craving for 
alcohol and the reduced likelihood of picking up the ﬁ  rst drink 
occur because the strength of the previous triggers—emotional, cognitive, or environmental—is attenuated.
Nausea following the ﬁ  rst few doses is the commonest unwanted

Nausea following the ﬁ  rst few doses is the commonest unwanted 
effect, occurring in about 10 per cent of patients. Concerns in the 1970s that naltrexone might cause dysphoria seemed to be sup-ported by statements from heroin addicts given naltrexone to help them abstain from opiates. However, laboratory studies andrandomized controlled trials in subjects who have not been opiate dependent have not found evidence of dysphoria or loss of feelings of pleasure.
(50)
Short-term administration of naltrexone reduced the rate of relapse to heavy drinking (odds ratio 0:62 in the meta-analysis of Bouza et al .
(43) but although individual studies have reported 
an advantage in rates of total abstinence, this is not upheld in meta-analysis.
(43)
Even though the dose is once daily, adherence has been low in 
some studies, and a beneﬁ  cial effect only demonstrable in compli-

(43)
ant patients.(51) Developed partly to improve compliance, a long-
acting injection given monthly has become available and found to be acceptable to patients. It was more effective in reducing relapse to heavy drinking than a monthly injection of the vehicle without active naltrexone.
(49)
When supervised oral naltrexone was compared to supervised 
disulﬁ  ram it was found to be less effective in preventing relapse 
to heavy drinking.(40) However, when oral naltrexone has been 
compared to acamprosate it was more effective.(52–54)

Opiate antagonists have a particular role in reducing relapse to heavy drinking in patients who will not or cannot attain abstinence. As well as prescribed as a daily dose, their targeted used has also been supported in patients trying to limit the amount consumed per session, when the patient takes a dose only on days when at risk of drinking or planning to drink.
(55,56)  Several studies have found 
that patient with a positive family history of alcohol dependence are more likely to beneﬁ  t from an opiate antagonist than those 
without.
Interactions. Opiate antagonists such as naltrexone will precipi-
tate an immediate opiate withdrawal syndrome if given to patients who are actively dependent on opiates, and will prevent pain relief of opiate analgesics.
Helping women with alcohol problems

It has been said that when a woman has an alcohol problem, there is a man in her life with a similar problem—usually her partner or her father. When the partner also drinks heavily, he should be invited to some joint therapy meetings. Some partners have adopted a controlling role, especially if the spouse has been unreliable in

455
managing the children or the money, or has driven while intoxicated. 
The patient may allow her resentment at this to fuel her drinking, and it may need months to help her to see how this has come about.
Low self-esteem is very common in such women, even in those 
who were conﬁ  dent before the drinking became problematic. The 
partner, while remaining ﬁ  rm about the unacceptability of her 
drinking, may need help to be more caring and positive, to show interest in what concerns her, and to show appreciation.
When helping women with alcohol dependence to abstain some 
of the following may be relevant:
X Help her to stop feeling taken for granted, and to know that she 
has a right to set limits on what others expect of her.
X Although guilt may be proportional to what she has put her 
family through by her drinking, it may not help. It may prevent her from asking for the conditions at home or work that would make it easier for her to stop drinking.
X Help her let go of resentments.

X Help her ﬁ  nd ways of recharging her batteries by, for example, 
taking up new interests or exercise.
X Talk with the partner, both alone and with her present. He may 
want to know that she acknowledges the strain on him. While still accepting complete responsibility for her drinking, she can let him know what he can do to help her.
X Self-help literature is available in many languages to help women 
improve self-conﬁ  dence and self-assertion.(57)
Treatment of coexisting disorders
Affective disorder
Depression is common in patients who are dependent on alcohol.

Depression is common in patients who are dependent on alcohol. 
The drinking may have alienated friends, family, or employer, with resulting feelings of hopelessness, guilt, and lack of direction. Alcohol can reduce appetite, energy, and sexual drive. The drinker wakes in the small hours of the night feeling anxious owing to the rebound wakefulness of alcohol withdrawal. Those signs and symp-toms suggesting depressive illness commonly clear with abstinence and help in tackling or tolerating personal problems and improv-ing relationships.
Sometimes (more often in women than in men) a depressive 
episode precedes the alcohol dependence, the patient begins to use alcohol as self-medication. Sometimes depressive symptoms continue despite abstinence. In these cases, antidepressants should be offered in the usual way.
(58,59) Relapsing alcoholism, secondary

(58,59) Relapsing alcoholism, secondary 
to depressive illness, is an indication for long-term antidepressants. Lithium is not a treatment for alcohol dependence itself, but is effective if alcohol dependence is secondary to manic–depressive disorder.
General practitioners and general psychiatrists often prescribe 
antidepressants to patients with alcohol dependence who are still drinking, because the patient has complained of low mood, insom-nia, or anxiety. There is no evidence that this will improve the drinking problem, and the period of alcohol withdrawal under benzodiazepine cover can be an occasion to withdraw the antide-pressant. Most depressive symptoms experienced while alcohol-dependent patients are drinking are alleviated with abstinence. Early-onset alcohol dependence, marked by novelty seeking and impulsivity, can be exacerbated by SSRIs.
(60,61)Anxiety and panic disorder

Some patients have had panic attacks for years before discovering that alcohol can end or prevent them. Others have a ﬁ  rst panic 
attack during alcohol withdrawal, but the attacks continue inde-pendently even during sustained abstinence. In this case, cognitive behavioural therapy and/or medication are indicated. Anxiety symptoms, which persist are predictive of relapse in the coming year.
(62) However, the majority of anxiety symptoms reported by 
alcohol-dependent patients resolve with abstinence(63,64)  and the 
weight of evidence is that adding speciﬁ  c psychological therapy 
aimed at the anxiety symptoms does not improve the drinking or the anxiety outcomes beyond that achieved by the treatment for the alcohol dependence.
(65,66) In Project MATCH, male patients

(65,66) In Project MATCH, male patients 
with social phobia allocated to 12-step facilitation (i.e. encourage-ment to attend AA) improved their drinking as much or even slightly more than those patients allocated to cognitive behaviour therapy (CBT) who would have received speciﬁ  c treatment for their 
phobia, though an advantage to CBT showed in female socially phobic patients.
(67)
One explanation for these ﬁ  ndings could be that attending to the 
anxiety might, for some patients, distract attention from the drink-ing, or could even seem to ‘justify’ their continuing to drink. It is also the case that some phobic patients report that attending AA helped them to overcome their social phobia.
Three studies suggest that the serotonin agonist buspirone can 
help reduce both drinking and anxiety.
(68) Tricyclic antidepressants

(68) Tricyclic antidepressants 
and selective serotonin-reuptake inhibitors ( SSRIs ) are prescribed 
to patients whose anxiety disorder persists despite abstinence. Some patients with long histories of alcohol dependence and severe panic disorder fail to respond to these medications or to CBT. For these patients the risk of complications from a prescription for a long-acting benzodiazepine such as chlordiazepoxide may be less than the harm that might accrue if bouts of excessive drinking persisted. If prescribed (and to do so is controversial), the benzodi-azepine should be dispensed in limited amounts. The prescription should be conditional on abstinence from alcohol, perhaps aided by disulﬁ  ram, if necessary. ‘As-required’ use (e.g. for travelling on

public transport) helps to limit the development of tolerance, even though in theory it may perpetuate phobic beliefs. This method 
probably commits the patient to long-term use and an enduring 
risk of escalation.
Treating alcohol-dependent patients with antipsychotic medica-
tion when there is no psychotic illness may increase their drinking and should be avoided.
(69,70)
Residential and inpatient treatment
It is debatable whether a period of inpatient treatment can improve the eventual outcome. Some studies have compared outcomes after patients have been randomly allocated to either inpatient or outpatient treatment. Usually no difference has been found. However, the interpretation of these results and their extrapolation to clinical reality has been debated. Finney et al.
(71) concluded that 
the studies often lacked statistical power. Furthermore, the more seriously affected patients had sometimes been excluded before randomization.

(72,73) While evidence that it is inpatient treatment 
rather than intensity of treatment which improves outcome is lacking,
(74,75)  admission to hospital can provide valuable respite for 
the drinker and the family when life is severely disorganized because 4.2.2.4 treatment of alcohol dependence

SECTION 4  clinical syndromes of adult psychiatry 456
drinking is out of control. Perhaps such respite need not be offered 
in a relatively expensive medical environment. However, if the patient has become suicidal as difﬁ  culties increase or has developed 
serious medical complications, then hospital admission may be indicated, ideally to specialized facilities. Longer stays in hospital are not supported by research. For example, Trent
(76) found no 
evidence of worse outcome when the United States Navy reduced the length of its inpatient alcoholism treatment programme from 6 to 4 weeks. The role of inpatient treatment is considered further in Chapter 4.2.2.5.
Matching patients to treatments

It is recognized that people with alcohol dependence present a range of problems, come from various backgrounds, and have dif-ferent personality characteristics. Some have no accompanying emotional disturbance; others have a psychiatric disorder. The poor outcomes of treatment for alcohol dependence have been attributed to their use with unsuitable patient, and better matching of patients to treatments has been sought. A North American study of 1726 outpatients (Project MATCH) set out to test hypotheses about matching treatments to patients. Three treatments were studied, each established in previous randomized controlled trials as more effective than ‘supportive therapy’: motivational enhancement therapy, cognitive behavioural therapy, and instruction in the AA approach with encouragement to take part in AA meetings (‘12-step facilitation’).
Few matching effects reached statistical signiﬁ  cance. In patients

Few matching effects reached statistical signiﬁ  cance. In patients 
recruited from outpatient clinics, those who scored high on anger at initial assessment averaged 85 per cent of abstinent days if they had been allocated to motivational enhancement therapy compared with 75 per cent if they had been allocated to 12-step facilitation or cognitive behavioural therapy.
(77) In the ﬁ  rst year of 
follow-up, patients with initially less severe psychiatric symptoms had more abstinent days after the 12-step facilitation than after cognitive behavioural therapy. Patients with critically high psychi-atric severity did no better with cognitive behavioural therapy.
(77)
Another marker of who beneﬁ  ts most from AA emerged in the 
3-year Project MATCH data. Patients who came from a social milieu where they mixed a lot with other drinkers owing to family, neighbourhood, or work inﬂ  uences did better if they had received

3-year Project MATCH data. Patients who came from a social milieu where they mixed a lot with other drinkers owing to family, neighbourhood, or work inﬂ  uences did better if they had received 
12-step facilitation than with either cognitive behavioural therapy or motivational enhancement therapy.
(34)
There are several reasons for the absence of evidence of other 
powerful predictors of treatment outcome in the Project MATCH data. Perhaps the key behaviour—not taking the ﬁ  rst drink—can 
be arrived at in different ways.
Some clinical situations
Morbid jealousy
This is discussed in Chapter 4.4.
The homeless alcohol-dependent person
It is difficult to conduct randomized controlled studies with adequate follow-up to test the efﬁ  cacy of interventions to reduce

It is difficult to conduct randomized controlled studies with adequate follow-up to test the efﬁ  cacy of interventions to reduce 
drinking and improve social conditions for the homeless, andfew answers have been found. A brief hospital admission to ‘dry out’ and assessment for transfer to residential care may result in transient improvement in physical health and is more humane than 
prison. However, supporting evidence is lacking. The structured intensive outpatient intervention, ‘community reinforcement approach’ , has been shown in a North American study to reduce drinking (corroborated by improvement in serum γ-glutamyl 
transferase) and increase the number of clients at work and in sat-
isfactory housing.
(78) The community reinforcement approach 
combined an offer of free housing, a place at a ‘job club’ to assist with ﬁ  nding employment, training in problem-solving skills, com-

munication, goal-setting, refusal of drinks, and independent living. Patients had access to an alcohol-free social club. The housing offer was contingent on sobriety and some evidence of saving money. Continuation in the housing was contingent on sobriety checked by breathalyser. Disulﬁ  ram had been shown to improve the effects 
of the community reinforcement approach.
(15,79)
Young people
There is a dearth of evaluation of programmes to help young peo-ple with alcohol problems. AA groups may have teenage members. When education or employment is in jeopardy, young people may accept disulﬁ  ram, supervised perhaps by the family. However, with-

out the support of a non-drinking peer group (which they would have in AA), most young people will try again and again to resume ‘social drinking’ . Job or marriage commitments sometimes alter the pay-off matrix sufﬁ  ciently for recovery to be sustained. Otherwise, 
it may not be until age 30 that the young person is sufﬁ  ciently con-
vinced that he or she cannot control drinking and takes serious steps to seek help.
Employment referrals
It is common for individuals to seek help when their drinking has put their job in jeopardy. Having a job helps recovery, and for the person to lose employment while paying only lip-service to treat-ment is common and disheartening for all. The psychiatrist should ﬁ nd out whether disciplinary procedures are in motion or threat-

ened. It can be helpful if the psychiatrist and the patient are told this directly by the employer. If the consultation is part of an under-taking under a company ‘alcohol and drugs policy’ , the patient may have given permission for the psychiatrist to answer the employer’s request to know whether he or she is attending and following advice.
Patients who are on the point of dismissal may offer to take 
disulﬁ  ram supervised in the company’s occupational health or wel-
fare department. This can bring about recovery and employment 
for as long as the threat of dismissal remains, and sometimes 
afterwards.
(80)
The liver transplant candidate

(80)
Some transplant centres require a demonstration of months of abstinence, to show commitment, before offering transplant to a patient with alcoholic liver disorder. Other centres have no such restrictions. From 6 to 80 per cent of transplant recipients, varying between centres, have recommenced drinking and exceeded safe limits by the end of the ﬁ  rst year. Their eventual outcome in terms 
of quality of life and psychiatric health is no worse than for other transplant patients, and there is no evidence to support demanding lengthy preoperative abstinence. However, patients who relapse to problematic drinking are more likely to have had a history of deﬁ nite alcohol dependence, and/or depressive illness.
(81,82)

457
Physicians as patients
Alcohol dependence is commoner among doctors than among 
most other occupational groups, other than those groups who are employed in the alcohol beverage manufacturing or retailing. Doctors’ outcome, once in treatment, tends to be good if they can return to their practice. This is probably partly due to the require-ment by the licensing body that ‘impaired physicians’ accept moni-toring by an independent specialist to corroborate that they are following advice and continuing to progress.
(83,84)
Doctors’ reluctance to accept help for their illnesses, and their

(83,84)
Doctors’ reluctance to accept help for their illnesses, and their 
tendency to treat themselves, is well known and true for substance misuse. Initial denial often means that problems escalate until there are disciplinary or Court proceedings and attempts to treat their own alcohol dependence may result in dependence on other sub-stances. In some instances, where there is any risk to safety of the doctor’s patients, the professional licensing body should be informed if not already involved.
The alcoholic doctor should be treated in the same way as a lay 
person. The partner should be invited to the interview. Ideally, information should be obtained from the employer or from a col-league about the nature of any problems at work or any disciplin-ary action, actual or threatened.
In some countries there are support groups for recovering doc-
tors and dentists who meet together and are ready to offer advice 
and encouragement to individuals and their families.
Follow-up

Follow-up
Systematic follow-up has been shown to improve outcomes.(17,85)
Early detection of relapse is important, and is aided by regular 
contact with the family or the workplace, a breathalyser test at interview, and tests for blood markers of drinking ( γ-glutamyl 
transferase or carbohydrate-deﬁ  cient transferrin).
(86) Objective 
markers are required when a patient requests a report for a Court, the driving licence authority, or an employer.
Some guiding principles
Research into alcoholism spanning 50 years has shown that the attitudes of the agency and the therapist inﬂ  uence patients’ out-
come, as they may do for many illnesses. The therapeutic alliance is a strong predictor of outcome in the treatment of alcohol depen-dence.
(87) However, agencies must also be prepared to set limits on

(87) However, agencies must also be prepared to set limits on 
drunken behaviour at the clinic and telephone calls when intoxi-cated. And for patients who repeatedly relapse, resumption of treatment should sometimes be made conditional on complying with a new treatment plan, such as supervision of medication.
(88)
Showing respect, enhancing dignity, conveying accurate empathy, 
adopting objective and not moral criteria, involving the family, 
and reducing hurdles to seeking help have been shown to improve 
compliance, and often outcome, for alcohol dependence.
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4.2.2.5 Services for alcohol use disorders
A spectrum of disorders needing a range of 
services
The provision of services for alcohol use disorders has been driven

services
The provision of services for alcohol use disorders has been driven 
by the prevailing view of their nature and prevalence. Following the Second World War, the disease concept of alcoholism gained increasing support in both the United States (US) and the United Kingdom (UK).
(1) According to this concept, alcoholism is an all-
or-nothing phenomenon affecting a relatively small subgroup of the population, and requires intensive specialist treatment. In the UK this led to the development of specialist alcohol treatment cen-tres with an emphasis on intensive inpatient treatment involving group therapy, often with close affiliation to the Alcoholics Anonymous ( AA) fellowship. Such programmes tended to be tar-
geted at relatively socially stable men, and catering for the more severely alcohol dependent.
(2)
In the 1970s and 1980s came a recognition that there existed a

(2)
In the 1970s and 1980s came a recognition that there existed a 
much wider range of alcohol-related problems in the population than would meet the narrow criteria of alcoholism or alcohol dependence, but which might nevertheless beneﬁ  t from inter-
vention. Research began to show that alcohol problems existed on a continuum of severity and thus might not necessarily require intensive specialist treatment with a lifelong goal of complete absti-nence from alcohol. Screening and brief intervention with pres-ymptomatic heavy drinkers in the primary care or general hospital medical ward setting could be effective in reducing excessive alco-hol consumption and alcohol-related harm.
(3,4) This led to the 
proposal that greater beneﬁ  t could be accrued from less intensive 4.2.2.5 services for alcohol use disorders

SECTION 4  clinical syndromes of adult psychiatry 460
approaches aimed at the large number of hazardous drinkers, 
than more intensive and expensive interventions catering for the minority of very heavy drinkers: the ‘preventive paradox’ .
(5)
In a ground-breaking report, the US Institute of Medicine advo-
cated ‘broadening the base of treatment for alcohol problems’ .(6)

(5)
Recognizing the potential for increased prevention and treatment activity in health care personnel without specialist addiction training (e.g. general practitioners, physicians, social workers), and the limitations of expanding specialist treatment given the high prevalence of alcohol misuse, the report emphasized the need for an expanded range of locations and methods of intervention, across the spectrum of alcohol use disorders (see Fig. 4.2.2.5.1). Importantly however, the report also recognized that alcohol use disorders are heterogeneous, and different types of disorders are likely to require different types or intensities of treatment, that is, the need to match treatments to the nature of the presenting problem.
Since this report there has been some progress made towards 
increasing the range and accessibility of treatment. However, in

increasing the range and accessibility of treatment. However, in 
some cases this has been disappointing. This chapter describes the 
range and organization of treatment approaches and explores the barriers to implementation of a comprehensive system of care for alcohol use disorders. The evidence suggests that we have a long way to go to deliver an optimal level of access to alcohol treatment for those in need. The evidence on the cost-effectiveness of alcohol treatment is discussed, and consideration is given to the needs of special groups in the population who may ﬁ  nd access to treatment more difﬁ  cult. The main conclusion is that on the basis of the exist-

ing research evidence there remain considerable opportunities to expand and improve treatment services for alcohol use disorders. This will require further training and dissemination initiatives and the political will and funding to achieve this throughout the health system.
Location and intensity of treatment
Brief interventions
There has been considerable research interest in the potential of brief interventions in primary care, and to a lesser extent in the general hospital.
(7) There are several potential advantages in con-
ducting treatment interventions in primary care. Patients with alcohol use disorders consult their general practitioner more fre-quently than other patients. Excessive drinkers identiﬁ  ed by screen-
ing in primary care are largely at an earlier stage in their drinking career and are potentially more likely to beneﬁ  t from brief early

ing in primary care are largely at an earlier stage in their drinking career and are potentially more likely to beneﬁ  t from brief early 
intervention than more severely dependent drinkers presenting to specialist treatment services. Further, primary care is often seen as less stigmatizing than a specialist clinic. Brief interventions typi-cally involve opportunistic screening using tools such as the AUDIT questionnaire
(8) or other shorter variants,(9) followed by 5–30 min. 
of brief intervention conducted by a practitioner who does not have training in specialist alcohol treatment.
Several studies have demonstrated the effectiveness of screening 
and brief intervention in hazardous drinkers in primary care. In a large randomized controlled trial, Wallace et al.
(4) found that brief 
intervention was more effective than a control treatment in reduc-ing alcohol consumption and γ-glutamyl transferase at 1-year 
follow-up. Similar ﬁ  ndings were obtained in a large World Health

follow-up. Similar ﬁ  ndings were obtained in a large World Health 
Organization multicentre trial.
(10)
Fewer screening and brief intervention studies have been con-
ducted in the general hospital setting. A recent meta-analysis of this literature showed no difference between intervention and con-trol in this setting.
(11) However, some recent studies have shown 
beneﬁ  ts of screening and brief intervention in accident and emer-
gency departments. One UK study showed reduced alcohol consumption and fewer reattendances in A&E attenders identiﬁ  ed 
by screening and referred to an alcohol health worker.
(12) Another 
UK study in young men with alcohol-related facial injuries found that brief intervention signiﬁ  cantly reduced alcohol consumption 
and alcohol-related problems.
(13)
Meta-analyses of brief interventions have mostly found advan-

(13)
tages of brief intervention over control treatments with effect sizes of 10–20 per cent on reduced alcohol consumption at 1 year.
(14–16)
Some earlier reviews concluded that brief interventions are at least as effective as more intensive specialist treatments. However, the populations studied in brief intervention trials are heteroge-neous.
(17) Most trials have been conducted with opportunistic 
screening in non-treatment seeking populations in primary care. A smaller number have compared brief interventions to more intensive treatments in specialist alcohol treatment settings. A recent review found that brief interventions are effective only in less severe alcohol disorders in the context of opportunistic screening.
(15)
There are barriers to implementation of brief intervention in 
non-specialist settings, which may limit its effectiveness. In a UK national survey,

(15)
(18,19) it was found that general practitioners and Fig. 4.2.2.5.1 A spectrum of responses to alcohol problems. 
(Reprinted from D. Raistrick, N. Heather, and C. Godfrey, (2006), Review of the 
effectiveness of treatment for alcohol problems , National Treatment Agency 
for Substance Misuse, London © 2001–2008 National Treatment Agency.) The triangle represents the general population, with the spectrum of alcohol 
problems experienced by the population shown along the upper side of the

problems experienced by the population shown along the upper side of the 
ﬁ  gure. Responses to these problems are shown along the lower side. The dotted lines suggest that primary prevention, simple brief intervention, extended brief intervention and less-intensive treatment may have effects beyond their main target area. Although the ﬁ  gure is not drawn to scale, the prevalence in the population of each of the categories of alcohol problem is approximated by the area of the triangle occupied; most people have no alcohol problems, a very large number show risky consumption but no current problems, many have 
risky consumption and less serious alcohol problems, some have moderate 
dependence and problems and a few have severe dependence or complicated alcohol problems.Alcohol problems None
Public health programmes - primary preventionSimple brief interventions in generalist settingsExtended brief interventions in generalist setting            Less-intensive treatment in

generalist or specialist settingsHazardous drinking
Harmful drinking
Severely dependent
       drinking
            More intensive
specialist treatmentModerately dependent
         drinking

461
primary care practice nurses were reluctant to engage in screening 
and brief interventions because of a perceived lack of training and support to carry-out this work. Effective implementation of large-scale screening and brief intervention programmes will require attention to the training and support needs of non-specialist personnel. Further, screening programmes will identify more severely alcohol dependent drinkers who may not respond to brief interventions alone. Thus, effective working arrangements between generalists and specialists are needed. Drummond
(20) has also 
questioned the generalizability of brief intervention researchﬁ ndings in the typical clinical setting, given the large number of 
exclusions in research studies and a lack of pragmatic trials.
Specialist treatment in inpatient settings

The main treatment response to alcohol use disorders continues to be delivered by specialists, although this is mostly delivered in the community rather than in inpatient settings. There has been exten-sive research on the location and intensity of specialist treatment. An early inﬂ  uential study was that of Edwards et al .
(21) in which 
100 alcohol-dependent men referred to the Maudsley Hospital in London were randomized to receive either intensive specialist treatment, including specialist inpatient care, or a single session of counselling. At 1-year follow-up there was no difference in outcome between the two treatments. It was concluded that the reliance on intensive treatments up to that time was called into question by the ﬁ  ndings. This controversial study gave rise to con-

siderable debate and several studies have subsequently investigated the same issues. Another British study attempted to replicate the Edwards study and found only modest differences between advice only and extended treatment in a randomized controlled trial at 2 years’ follow-up.
(22) There were, however, no differences between 
treatments in abstinence rates or alcohol consumption level during follow-up. However, a later follow-up of the Edwards cohort found that more severely dependent drinkers benefited more from intensive treatment.
(23)
In a larger study in the US, employees who were identiﬁ  ed as 
drinking excessively were randomized to one of the three options: compulsory inpatient treatment, compulsory AA attendance, or a choice of these two options.
(24) At 2-year follow-up there were no

(24) At 2-year follow-up there were no 
differences between the groups in terms of work-related outcome measures. However, drinking-related measures the inpatient group had the best, and the AA group the poorest outcome, with the choice group having an intermediate outcome. The compulsory AA group was more likely than the others to require subsequent inpatient treatment. However, the length of inpatient treatment does not appear to inﬂ  uence outcome signiﬁ  cantly.
(25,26)
Studies comparing inpatient versus outpatient alcohol detoxiﬁ  -
cation have generally found the two approaches to be equally effec-tive. For example, Hayashida et al .
(27) randomized male military 
veterans to inpatient and outpatient detoxiﬁ  cation. At 6 months’

veterans to inpatient and outpatient detoxiﬁ  cation. At 6 months’ 
follow-up no differences in outcome were found between the two groups. Indeed, outpatient detoxiﬁ  cation is generally regarded as 
the treatment of choice for the majority of patients. It should be noted, however, that studies comparing inpatient and outpatient treatment (including detoxiﬁ  cation) have tended to exclude patients 
with particularly poor prognosis (e.g. poor social circumstances, severe psychiatric or physical comorbidity, those at risk of harm to themselves or others). Hence, the clinician needs to interpret the research evidence with caution in applying it to patients in thetypical clinical setting. However, it is probably safe to assume that 
in less complicated alcohol dependence there is no evidence of an advantage of inpatient over outpatient treatment.
A recent randomized trial by Rychartic et al.
(28) assigned alcohol

(28) assigned alcohol 
dependent patients to inpatient, intensive outpatient, or standard 
outpatient treatment. Following treatment inpatients had reduced jail and subsequent inpatient episodes, and those with greater alcohol dependence or impaired cognitive function had better outcomes with inpatient treatment.
Overall, the majority of studies that have compared intensive

Overall, the majority of studies that have compared intensive 
specialist treatment with less intensive treatment have not supported the use of more intensive approaches. However, most of these studies excluded patients with more complex needs. Few studies have examined the interaction between treatment setting and problem severity. The emerging evidence now is that alcohol dependent patients with more complex needs (more severe alcohol dependence, psychiatric comorbidity, cognitive impairment, poor social circumstances, or support) are more likely to beneﬁ  t from 
inpatient treatment.
(9)
Community-based specialist treatments
The growth of studies questioning the value of specialist inpatient treatment and a move towards cost containment in health care have led to a shift in resources to treating alcohol use disorders in community settings. In the US for example 87 per cent of specialist alcohol treatment is delivered on an outpatient basis.
(29) A similar

(29) A similar 
survey in England found that 69 per cent of specialist alcohol treat-ment agencies were community based.
(30)
Apart from the potential advantage of lower cost, community-
based treatment provides the least social disruption for the indi-vidual and offers the opportunity to mobilize existing community resources to support sustained recovery. In the UK, the past 30 years have seen the widespread development of the community alcohol team (CAT) model of treatment following the original Maudsley Alcohol Pilot Project.
(31) The main principle of the CAT 
model is that the specialist multi-disciplinary team (typically con-sisting of specialist medical, nursing, social work, and psychology staff) work to train and support generic teams, mainly in primary care, to manage alcohol use disorders more effectively. In practice, CATs have tended to ﬁ  nd difﬁ  culty in avoiding becoming involved

in a more traditional specialist role, often providing direct care for alcohol use disorders in the face of reluctance on the part of primary care personnel to take on this work.
(32)
There has been remarkably little research conducted to evaluate 
the CAT model. One study randomly allocated 40 problem drink-ers referred to the specialist alcohol treatment clinic at the Maudsley Hospital to receive either routine specialist treatment or ‘shared care’ .
(33) Following specialist assessment, the shared care group was 
returned to the care of their general practitioner, who was then supported by the specialist CAT. Shared care within this model included advice and training for the general practitioner, a shared treatment plan, regular phone contact between specialist and gen-eral practitioner, and the offer of further specialist care should the patient remain unchanged or deteriorate. At 6 months’ follow-up the specialist and shared care groups both showed signiﬁ  cant

improvements, but there was no difference in outcome between the two groups.
Another study in Scotland evaluated the efﬁ  cacy of a home 
detoxiﬁ  cation service compared with minimal intervention in a 4.2.2.5 services for alcohol use disorders

SECTION 4  clinical syndromes of adult psychiatry 462
randomized controlled trial in 95 patients referred by their general 
practitioner.(34) At 6 months’ follow-up the home detoxiﬁ  cation 
group remained abstinent twice as long after treatment than the minimal intervention group.
The ‘community reinforcement approach’ has been demonstrated 
to have beneﬁ  ts in the treatment of alcohol dependence in the 
US.
(35) This approach aims to provide reinforcers for abstinence 
from alcohol including positive family support, help in ﬁ  nding 
employment, membership of an alcohol-free social club, and alcohol counselling. The specialist treatment input aims to ensure that these supports are put in place. There is some evidence from small-scale controlled trials
(35,36) that this approach is effective in 
reducing alcohol consumption and improving social adjustment compared to standard treatment, but it has not so far been fully evaluated, and has never been tested in the UK.

Another variant on the CAT approach has been the evaluation of 
community psychiatric nurse (CPN) aftercare following specialist inpatient treatment.
(37) One study in the UK evaluated the effec-
tiveness of regular CPN follow-up consisting of weekly 1 to 2 h visits to the patient’s home for a period of 6 weeks post-discharge from inpatient care, followed by less frequent visits up to 1 year. The home-based sessions involved advice, support, counselling, partner involvement, and encouragement to attend AA. This was compared to routine 6-weekly hospital appointments. The study, which involved a non-randomized design, found significant improvements in abstinence and engagement in support in the CPN approach compared to the routine aftercare group.
There is growing interest in the potential application of Assertive

There is growing interest in the potential application of Assertive 
Community Treatment (ACT) approaches for alcohol dependence, particularly for patients with more severe, complex and chronic problems who are difficult to engage in standard treatment approaches. This borrows from the experience of ACT in severe 
mental illness
(38) and acknowledges that for some patients, alcohol 
dependence is a chronic disorder that in these cases may be more suited to a ‘disease management’ model of care, commonplace in treatment of many physical illnesses such as diabetes or hyper-tension. Assertive approaches appear promising in alcohol depen-dence,
(39) but a deﬁ  nitive trial of ACT is needed.
In summary, the CAT model of alcohol service delivery has been

In summary, the CAT model of alcohol service delivery has been 
widely implemented in the UK in advance of clear evidence of its effectiveness. Evidence is emerging showing at least the equivalence, and in some cases, the superiority, of outcome from community-based services compared with more traditional inpatient treatment approaches. However, the CAT approach is implemented in a range of ways in the UK, and encompasses many different models and speciﬁ  c interventions. More research is needed to evaluate the 
cost-effectiveness of community alcohol team approaches and to identify the speciﬁ  c elements and methods that contribute to 
treatment effectiveness.
Matching and stepped care
The Institute of Medicine report emphasized the need to match the level of intervention to the severity and nature of the presenting problems.
(6) There is some empirical evidence of matching effects

(6) There is some empirical evidence of matching effects 
in relation to both inpatient and outpatient treatment.(40) Up until 
recently, however, matching effects have generally been explored in post hoc  analyses in studies that lacked sufﬁ  cient statistical power. 
The Project MATCH study in the US aimed to assess a wide range of matching hypotheses in a prospective design, but found no strong matching effects
(42) (see Chapter 4.2.2.4). However, it should 
be noted that most controlled trials, including MATCH, excluded the more complex patients, including those with limited socialsupport and those with severe psychiatric comorbidity. This tends to work against ﬁ  nding matching effects as the study sample
lacked clinical heterogeneity.
(43) Further, many of the patient
and treatment programme characteristics likely to mediatetreatment matching and treatment effectiveness, remain largely unresearched. The matching results of a similar trial in the UK are awaited.
(43)

(43)
Stepped care is an alternative method of matching treatments to 
patient needs that has become accepted in the ﬁ  elds of smoking 
intervention and general medicine. Until now it has received rela-tively scant attention in the alcohol ﬁ  eld. In essence, stepped care 
involves initially providing relatively low-intensity treatments, and only offering more intensive treatments to those who fail to respond.
(44) This provides a potentially resource-efﬁ  cient means 
of delivering treatment, and provides clinicians with clinical algorithms. A recent trial of alcohol screening in primary care compared stepped care intervention with minimal 5 min of advice delivered by a practice nurse.
(45) In the stepped care group received

(45) In the stepped care group received 
an initial 40 min session of Behaviour Change Counselling deliv-ered by a trained practice nurse who then followed up the patients (Step 1). Those who did not respond to Step 1 were referred to four sessions of Motivational Enhancement Therapy delivered by trained alcohol counsellors (Step 2). Finally those not responding to Step 2 were referred to more intensive treatment delivered by a CAT (Step 3). The study found no signiﬁ  cant difference in alcohol 
consumption at 6 months, which may in part be due to a small sample size. However, the stepped care intervention was more cost-effective than minimal intervention, mainly through reduced health care and criminal justice costs.
Overall, few community-based studies have found signiﬁ  cant 
treatment matching effects. But this may be in part due to exclu-
sion of the most severe cases. Some studies have found advantages

sion of the most severe cases. Some studies have found advantages 
of inpatient compared with community treatment for patients with more severe and complex needs as described above. A more prom-ising approach is stepped care, which is effectively pragmatic matching: that is patients not responding to less intensive treat-ments receive more intensive treatments. This now forms an important principle of the national framework for alcohol services in England.
(46)
Cost-effectiveness of alcohol treatment
With a trend towards containment of health care costs in industri-alized societies, there has been an increase in the application of health economic research in the alcohol treatment ﬁ  eld. It has been 
estimated that the annual cost to society of alcohol misuse is in the region of US$184 billion in the US
(47) and £20 billion in the UK.(48)

In comparison, the direct treatment costs of alcohol use disorders by specialist treatment agencies amounted to approximately US$7.5 billion in the US and about £217 million in the UK.
(47,30)
Thus there is a need to demonstrate the cost-effectiveness of treatments for alcohol use disorders.
Until recently, research on cost-effectiveness has been largely 
speculative and not based on direct estimates of cost beneﬁ  ts. 
In a landmark study, Holder et al.
(49) provided a ‘ﬁ  rst approxima-
tion’ of the cost-effectiveness of treatment. In their analysis they

463
used a combination of ﬁ  ndings of efﬁ  cacy from clinical trials, 
typical costs of different treatments, and recommendations from experts and treatment providers about appropriate treatment approaches. While noting the lack of studies directly assessing the cost-effectiveness of treatments, they concluded the cost of care was inversely correlated with evidence of effectiveness. They also noted that those treatments with the highest cost and lowest evidence of effectiveness were amongst the most prevalent in the North American treatment system. While this review has been criticized on methodological grounds, it has stimulated an impor-tant debate and has contributed to an increasing number of clini-cal trials including a health economic component in outcome evaluation.
Cost-effectiveness analysis, which takes a societal perspective

Cost-effectiveness analysis, which takes a societal perspective 
rather than a narrow intervention cost perspective, provides a better measure of the overall impact of an intervention. These wider costs include patient out-of-pocket costs, lost productivity, unplanned health care utilization (e.g. admissions with alcohol-related physical and mental illnesses, primary care utilization), criminal justice costs, accidents, premature deaths, social work involvement, childcare costs, and costs associated with illnesses in relatives and carers.
(50)
Also important in cost-effectiveness analysis is the estimation of 
improvements in quality of life following an intervention. This is beginning to be studied in the alcohol treatment ﬁ  eld. Quality

improvements in quality of life following an intervention. This is beginning to be studied in the alcohol treatment ﬁ  eld. Quality 
of life can be measured in a variety of ways (e.g. Euroqol, Short Form 36). In a randomized controlled trial an estimate of the difference in Quality Adjusted Life Y ears (QALYs) can be compared between treatment and control groups. The National Institute of Clinical Excellence (NICE) in the UK determines which treatments should be funded by the National Health Service (NHS) based on the available evidence. NICE regards a net cost per QALY, taking into account the costs of treatment and the savings to society, of £20 000 or less to be the maximum cost acceptable to implement the treatment in the NHS. Alcohol misusers typically have a much lower quality of life than non-alcohol misusers. One study com-
pared quality of life in alcohol dependent drinkers before treatment

pared quality of life in alcohol dependent drinkers before treatment 
with controls. Mean quality of life measured by the Euroqol (EQ5D) was 0.57 in the alcohol dependent group compared to age matched controls: 0.9 (1.0 being the best possible quality of life and 0 being death).
(43) However, a recent review found that while 
treatment signiﬁ  cantly reduces alcohol consumption and societal 
costs, it has a limited impact on quality of life.(9)
A recent review of cost-effectiveness examined the available lit-
erature on alcohol interventions.(9) In terms of intensive specialist 
alcohol treatment it was estimated that providing evidence-based alcohol interventions would result in a saving of £5 for the public sector for every £1 spent. However, it was noted that several studies showed an initial increase in costs in people newly entering alcohol treatment. This is likely to be because people not in treatment and in an active drinking phase ﬁ  nd it harder to access services, and

specialist alcohol services assist patients to address outstanding health and social care needs. Cost savings as a result of treatment therefore need to be examined over the longer term (>1 year). Comparing individual specialist interventions including pharmacotherapies and psychosocial interventions one review found the net health cost per death averted ranged from −£3073 to 
£2076 for most of the interventions that also provided signiﬁ  cant 
clinical improvements.
(51)There is now good evidence that brief intervention in hazardous/
harmful drinkers is highly cost-effective. Fleming et al .(52) found 
that, as well as reducing excessive drinking, there was a reduced length of hospitalization during the 12-month follow-up period. In addition, while brief intervention cost more than minimal intervention, this cost was more than offset by reductions in subse-quent health care, criminal justice, and road trafﬁ  c accident costs

(US$56 000 savings per US$10 000 intervention costs). An analysis of several brief intervention studies found the cost per life year g ained
was approximately £2000, well within the NICE deﬁ  nition.
(53)
There is considerable scope for further development of health 
economic research in the alcohol ﬁ  eld. This will prove important in 
providing health care commissioners with appropriate information to make rational decisions in the provision of cost-effective evi-dence-based services for alcohol use disorders. (For a further account of cost-effectiveness analysis, see Chapter 7.7.)
The availability of alcohol services
The availability of alcohol services is likely to affect the overall impact of treatment at a whole population level. There is some evi-dence that the availability of alcohol treatment services is related to the prevalence of alcohol use disorders at a population level. Mann et al .
(54) found that increased treatment services in Ontario,

(54) found that increased treatment services in Ontario, 
Canada, were associated with decreased hospital discharges for liver cirrhosis. A similar study in North Carolina examining the 20-year period between 1968 and 1987 found an association between increased alcohol treatment admissions and decreased cirrhosis mortality. Further, Mann et al .
(55) found a relationship 
between AA membership and alcohol-related problems including cirrhosis mortality rates in the US, Canada, and other countries. They estimated that a 1 per cent increase in AA membership was associated with a 0.06 per cent decrease in cirrhosis mortality. These studies of course demonstrate associations rather than causal links between treatment availability and prevalence, but do provide support to the hypothesis that access to treatment could have an impact at a population level.
The National Drug and Alcohol Treatment Utilization Survey 
(NDATUS ), which is a national census of public and private treat-

ment programmes in the US, provides a unique data set to study treatment availability. It has been conducted intermittently since 1979 and provides a method to study trends over time. An analysis 
by the Institute of Medicine found large regional variations in the 
availability of treatment places.
(6) There was no association found

(6) There was no association found 
between treatment place availability and prevalence of alcohol misuse across states in the US. This points to the importance of ‘needs assessment’ in the rational allocation of public resources to fund treatment services. This involves a variety of data sources as indicators of alcohol use disorder prevalence in a particular locality, including general population surveys, mortality statistics (e.g. deaths from alcoholic liver disease), crime statistics (e.g. public drunkenness and driving whilst intoxicated arrests), and alcohol-related hospital admissions. Such indicators provide measures of relative ‘need’ in different localities, gaps between need and access to treatment, and can be used to direct resource allocation.
Examining data from NDATUS surveys between 1982 and 1993, 
Weisner et al.
(56) found an increase in activity over this period of

(56) found an increase in activity over this period of 
147 per cent. In the US the impact of managed care organizations, which aim to limit access to treatment on the basis of individual 4.2.2.5 services for alcohol use disorders

SECTION 4  clinical syndromes of adult psychiatry 464
need and cost, has yet to be fully established in relation to overall 
access to alcohol services. Such measures are likely to reduce the availability of inpatient services and to reduce the rate of readmis-sion for those with chronic alcohol problems.
A recent national needs assessment in England examined inter 
alia the regional variation in the prevalence of alcohol use disor-
ders and access to specialist alcohol treatment services.
(30) The

(30) The 
prevalence of alcohol dependence in adults was 3.6 per cent overall (men: 6 per cent; women: 2 per cent), varying from 1.6 per cent to 5.2 per cent across regions. The overall level of access to treatment also varied across regions. In England overall, 1 in 18 people with alcohol dependence gained access to treatment per annum (the Prevalence–Service Utilization Ratio). But this varied from 1 in 12, to 1 in 108 between the best and worst served regions. A ratio of 1 in 10 is regarded as a ‘low’ level of access and 1 in 5 a ‘high’ level in North America.
(57) Factors associated with better access included a 
greater number of treatment agencies, greater overall spending on treatment, and shorter waiting times.
Special groups

Specialist alcohol treatment services typically attract younger, male, single patients of lower socio-economic and educational back-ground, with more severe alcohol dependence. Relative to the prevalence of alcohol use disorders in the general population, women, older people, and people from ethnic minorities are typically under-represented, as are the homeless. Further, there are limited specialist alcohol services for young people. This is of particular concern as the prevalence of alcohol use disorders is increasing in young people in the UK.
Women
Thom and Green have identiﬁ  ed three main factors that may 
account for the under-representation of women in alcohol treat-ment.
(58) Women tend to perceive their problems differently from

Women
(58) Women tend to perceive their problems differently from 
men, less often identifying themselves as ‘alcoholic’ . This may in part be related to negative public stereotypes of female drinking and negative attitudes towards female problem drinkers amongst professionals. Women have also been found to perceive the ‘costs’ of entering treatment differently from men. This is particularly in relation to the perceived social stigma as well as other costs, both ﬁ nancial, in relationships, and in terms of losing their children into 
the care system. Finally, women often ﬁ  nd the services offered to be

the care system. Finally, women often ﬁ  nd the services offered to be 
less appropriate in meeting their needs than do men. Often special-ist alcohol services do not offer childcare or ‘women-only’ facilities. However, an increasing number of women are seeking help for alcohol use disorders, both in the US and the UK on the basis of general population surveys and surveys of treatment populations. In England we found that women with alcohol dependence 
were 1.6 times more likely to access treatment than men.
(30) This 
suggests that some of the barriers to access identiﬁ  ed by Thom 
and Green have been overcome. Nevertheless, more still needs to be done to provide alcohol treatment services that are sensitive to women’s needs. Further, there is a need to develop services catering for pregnant women.
(59)
Ethnic minority groups
The evidence concerning help-seeking in ethnic minority groups is complex (see Chapter 7.3). Harrison et al .

(59)
(60) have provided a review of the evidence. In the US, Hispanics tend to be under-
represented and African–Americans are over-represented in alco-hol treatment compared with the general population prevalence. However, interpretation of the evidence is complicated by the fact that household surveys tend to under-represent socially disadvan-taged individuals from ethnic minorities. Marmot et al.
(61) found

(61) found 
that cirrhosis mortality rates were elevated compared to the nation-al average for men from the Asian subcontinent and from Ireland, but lower than average for African–Caribbean men. In women, cirrhosis mortality was lower than average in Asian and African–Caribbean women but higher in Irish women. However, there were few cirrhosis deaths in total in ethnic minorities, which may lead to large errors in extrapolation to the whole population alcohol misuse estimates. In terms of alcohol treatment populations, studies have tended to ﬁ  nd higher rates of admission (per 100 000 
population) in Indian-, Scottish- and Irish-born people than in those born in the Caribbean or Pakistan. Differences in culturally related health beliefs and help-seeking, as well as service factors such as the availability of interpreters or treatment personnel from 
appropriate ethnic minority groups, may account for some of these 
differences. There remain few speciﬁ  c services for people from

differences. There remain few speciﬁ  c services for people from 
ethnic minorities, although some examples of good practice exist in the UK.
(60)
The homeless
There is a high prevalence of alcohol use disorders (as well as men-tal and physical health and social problems) amongst the homeless population, a group that is not typically well catered for by main-stream alcohol services (see Chapter 7.10.2). The prevalence of alcohol problems in the homeless has been found to be as high as 38 per cent in the UK
(62) and between 2 and 86 per cent in the US; 
typically the prevalence is between 20 and 45 per cent in North American studies.
(59) This has contributed to the development of 
speciﬁ  c alcohol services for the homeless and street drinkers,

speciﬁ  c alcohol services for the homeless and street drinkers, 
notably ‘wet’ hostels. In the ‘wet’ hostel, residents are able to con-tinue drinking but are cared for in an environment that is designed to minimize the harm associated with heavy drinking and to tackle issues associated with homelessness.
(59,62) Such facilities tend to be 
restricted to large urban centres and have restricted places com-pared to the number of street drinkers. Similarly, outreach services and ‘crisis centres’ have been developed to attract alcohol-misusing homeless people into treatment facilities.
(63) Often those entering 
‘wet’ hostels can subsequently be persuaded to undergo alcohol detoxiﬁ  cation and progress to ‘dry’ (or alcohol-free) supported 
accommodation.

The prevalence of alcohol use disorders is increasing in young people, particularly young women in the UK.
(48) The young are 
over-represented in alcohol-related road trafﬁ  c accidents, and 
alcohol is a leading cause of accidental death in this group. Alcohol 
misuse is also associated with unprotected sexual activity. 
Nevertheless, there are few specialist alcohol services for young people. Most initiatives have been directed at prevention and
health promotion in this group, but the evidence to support
these is lacking. This has led to the proposal that individuallytargeted interventions, for e xample by the primary health care team 
or in accident and emergency departments, are more likely to be 
(64)

465
Relatives and carers
Relatives and carers of people with alcohol use disorders often 
experience signiﬁ  cant social and psychological problems related to 
the drinking of a ‘signiﬁ  cant other’ . Alcohol use disorders are
associated with a high level of domestic violence and child neglect and abuse. Many specialist treatment programmes provide help and support to relatives and carers, and Al-Anon (for adult carers and relatives) and Alateen (for the young), which are afﬁ  li-
ates of AA, provide a widely available source of mutual aid for these groups.
Services for individuals with comorbidity
There is an increasing recognition of the problems associated with alcohol and other drug misuse and mental illness (see Chapter 4.2.2.3). Often alcohol misuse is complicated by multiple substance misuse. For example, in the Epidemiologic Catchment Area Study half of all patients with schizophrenia also had a sub-stance use disorder,
(65) and a recent British survey of psychiatric

(65) and a recent British survey of psychiatric 
inpatients found that half had an alcohol use disorder.(66) However, 
there is currently no consensus on the most appropriate treatment services for patients with comorbidity.
(67) Alcohol and substance 
misuse can be particularly problematic in the context of mental illness, and is associated with higher rates of violence and poor treatment outcome. Such patients are often poorly engaged with, and disruptive in mental health services, and typically have difﬁ  culty in engaging in alcohol or drug services. Assertive 
community outreach and integrated service models, covering both mental illness and substance misuse, have been advocated, but 
more research is needed to evaluate the cost-effectiveness of these approaches.
The alcohol treatment ﬁ  eld has seen considerable change over

The alcohol treatment ﬁ  eld has seen considerable change over 
the past 30 years. Some of this has been evidence based, and some has been largely politically driven, particularly in the pursuitof containing health care costs. On the positive side, a shift inpolicy from a limited number of treatment services catering only for the small minority of severely dependent drinkers, to more community orientated services with a greater emphasis on early identification and intervention, is to be broadly welcomed. However, in some places a move towards services catering for early stage ‘at-risk’ drinkers has been at the expense of losing servicesfor those with more severe alcohol problems.
(40) While the evi-
dence in favour of matching treatments to individual needs is

still at a relatively early stage of development, and clear evidenceof matching effects is not yet available, clinical practice needs tobe guided by pragmatic principles by which more intensive treat-ments are provided to more complex patients, and/or in a stepped 
care paradigm. It must be concluded that, despite a large research 
effort in evaluating intensive versus less intensive alcohol interven-
tions, there is still a long way to go in developing pragmatic clinical 
trials that evaluate effectiveness and cost-effectiveness of treatment 
in a way that can best advise practitioners in the typical treatment setting.
On the positive side, research has begun to address fundamental

On the positive side, research has begun to address fundamental 
health economic issues that are highly relevant to the rational funding of treatment services. Important in this is the development of health economic analysis in randomized controlled trials.The assessment of the impact of treatment availability on the preva-
lence of alcohol-related harm also represents a signiﬁ  cant advance.
Health services research that does not inﬂ  uence clinical practice

Health services research that does not inﬂ  uence clinical practice 
fails in its fundamental aim. For example, while there is a now considerable evidence base in support of brief intervention in the primary care setting, there is a resistance within primary care to adopt such approaches, often despite exhortations from govern-ments and professional bodies. Part of the problem may lie in the disparity between the priorities of public health, which is directed towards population level beneﬁ  ts of an intervention, and the 
priorities of the individual practitioner, whose ﬁ  rst duty is to the 
patient in his or her care.
(17) If the individual practitioner remains 
unconvinced about the value of a particular intervention for the patient, such public health policies are likely to fail even if they are supported by research evidence.
Similarly, as Holder et al.
(49) have pointed out, often treatment

(49) have pointed out, often treatment 
programmes continue to provide alcohol services that are not supported by research evidence. On occasions, but not exclusively, this criticism is levelled at private for-proﬁ  t agencies, with the 
implication that their motivation is ﬁ  nancial rather than being 
principally for the beneﬁ  t of their patients. In many cases, however, 
the evidence base is lacking because the fundamental research has not yet been conducted. Or, as in the case of self-help organizations such as AA, the methodology necessary adequately to evaluate an intervention would be extremely complex, or perhaps impossible, to conduct to the standard typically expected in evidence-based medicine (i.e. a randomized controlled trial).
Nevertheless, treatment research cannot occur in a vacuum. 
Research needs to take account of the funding environment in 
which treatment takes place. Further, treatment research needs to

which treatment takes place. Further, treatment research needs to 
provide answers to the key issues facing commissioners of health care. With the gradual improvement in the quality of treatment research over the past three decades
(68) and the development of 
more advanced health economic methods to evaluate treatment, the treatment research community is in a much better position than ever before to provide evidence to guide the rational develop-ment of treatment services for alcohol use disorders.
While many differences between health care systems exist in

While many differences between health care systems exist in 
different countries, the evidence points to the need for a wide spectrum of services to cater for different needs. The development of low-threshold community-based services should not occur at the expense of more specialized services for more severe alcohol use disorders. Similarly, a treatment system that provides only specialist services for the minority of severe cases misses a signiﬁ  -
cant public health opportunity to reduce the prevalence of alcohol use disorders through early, brief interventions.
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4.2.2.6 Prevention of alcohol-
related problems
Robin Room
Alcohol consumption is widely distributed in the population in 
most parts of the world, with abstainers in a minority among adults in most developing societies but in a majority in many less developed societies.
(1,2) Those qualifying to be diagnosed with 
an alcohol use disorder are usually a relatively small minority of drinkers.
On the other hand, alcohol is causally implicated in a wide 
variety of health and social problems. The WHO Global Burden of 
Disease  (GBD ) study for 2000 estimated that alcohol accounted

Disease  (GBD ) study for 2000 estimated that alcohol accounted 
globally for 4 per cent of the total health-related loss of disability-adjusted life years (DALYs), for 6.8 per cent in developed societies like those in Western Europe and North America, and for 12.1 per cent in Eastern Europe and Central Asia.
(3) In terms of where this 
burden appears in the health system, while psychiatric conditions (including dependence) and chronic physical disease are both important, casualties often play a predominant role. The GBD  2000 
study calculated that injuries accounted for 40 per cent of the DALYs lost worldwide due to alcohol.
(3)
The public health importance of acute effects of a particular

(3)
The public health importance of acute effects of a particular 
episode of intoxication underlies what is often described as the ‘prevention paradox’ . In many societies, a fairly substantial propor-tion of the population (particularly of males) gets intoxicated at least occasionally, and by that fact is at risk of experiencing and causing social and health harm from drinking.
(4) Preventing 
alcohol problems thus requires looking beyond the considerably smaller segment of the population diagnosable with an alcohol use disorder, or the even smaller segment receiving treatment for such a disorder.
A complication in preventing alcohol problems is that there is 
also evidence of a health beneﬁ  t from drinking in terms of reduced 
cardiovascular disease. This beneﬁ  t is, however, important mainly

cardiovascular disease. This beneﬁ  t is, however, important mainly 
for men over 45 and women past menopause, and can be attained with a pattern of very light regular drinking, as little as a drink every second day.
(5) There is thus little potential conﬂ  ict between 
taking alcohol as a preventive heart medication and any prevention policy short of total prohibition.
Simplifying somewhat, there are seven main strategies to mini-
mize alcohol problems. One strategy is to educate or persuade people not to use or about ways to use so as to limit harm. A second strategy, a kind of negative persuasion, is to deter drinking-related behaviour with the threat of penalties. A third strategy, operating in the positive direction, is to provide alternatives to drinking or to 4.2.2.6 prevention of alcohol-related problems

SECTION 4  clinical syndromes of adult psychiatry 468
drink-connected activities. A fourth strategy is in one way or 
another to insulate the use from harm. A ﬁ  fth strategy is to regulate 
availability of the drug or the conditions of its use. Prohibition of supply may be regarded as a special case of such regulation. A sixth strategy is to work with social or religious movements oriented to reducing alcohol problems. And a seventh strategy is to treat or otherwise help people who are in trouble with their drinking. We will consider in turn these strategies and the evidence on their effectiveness in reducing rates of alcohol problems in the population.
Education and persuasion
In principle, education can be offered to any segment of the popu-lation in a variety of venues, but it is usually education of youth in schools, which ﬁ  rst comes to mind in the prevention of alcohol

problems. Community-based prevention programmes, which may be also directed at adults, often also include an educational component.
Education offers new information or ways of thinking about 
information, and leaves it to the listener to draw conclusions concerning beliefs and behaviour. However, most alcohol educa-tion programmes go beyond this. A commonplace of the North American evaluative literature on alcohol education is that ‘knowledge-only’ approaches do not result in changes in behav-iour.
(6) School-based alcohol education has thus usually had a per-
suasional element, aiming to inﬂ  uence students in a particular 
direction.
Persuasion is directly concerned with changing beliefs or 
behaviours, and may or may not also offer information. Mass-media campaigns aimed at persuasion have been a very common component of prevention programmes for alcohol-related prob-lems, but persuasion can be pursued also through other media and modalities.

In most societies, public health-oriented persuasion about alco-
hol must compete with a variety of other persuasional messages, including those intended to sell alcoholic beverages. The evidence that alcohol advertising inﬂ  uences teenagers and young adults 
towards increased drinking and problematic drinking is becoming 
stronger.
(7,8) Even where alcohol advertising is not allowed on the 
mass media, these messages are conveyed to consumers and poten-tial consumers in a variety of other ways.
Evidence on effectiveness
The literature on effectiveness of educational approaches is domi-nated by studies from the United States on school-based education. This means that the alcohol education has usually been in the context of drug and tobacco education, and that the emphasis has been on abstention,
(9) or at least on delaying the start of drinking,

(9) or at least on delaying the start of drinking, 
in cultural circumstances where the median age of actually starting drinking is about 13, while the minimum legal drinking age is 21. In general, despite the best efforts of a generation of researchers, this literature has had difﬁ  culty showing substantial and lasting 
effects.
(10) There is a good argument from general principles for 
alcohol education in the context of consumer and health educa-tion, but there is little evidence from the formal evaluation litera-ture at this point of its effectiveness beyond the short term.
Persuasional media campaigns have also been a favourite modality 
in many places in recent decades for the prevention of alcohol problems. In general, evaluations of such campaigns have been able

in many places in recent decades for the prevention of alcohol problems. In general, evaluations of such campaigns have been able 
to demonstrate impacts on knowledge and awareness about substance use problems, but little effect on drinking behaviour. As with school education approaches, there are hints in the litera-ture that success may come more from inﬂ  uencing the community 
environment around the drinker—in terms of attitudes of signiﬁ  -
cant others, or popular support for alcohol policy measures—than from directly persuading the drinker him/herself. Thus, media messages can be effective as agenda-setting mechanisms in the community, increasing or sustaining public support for other preventive strategies.
(11)
Deterrence

(11)
In its broadest sense, deterrence means simply the threat of nega-tive sanctions or incentives for behaviour—a form of negative persuasion. Criminal laws deter in two ways: by general deterrence, which is the effect of the law in preventing a prohibited behaviour in the population as a whole, and speciﬁ  c deterrence, which is the 
effect of the law in discouraging those who have been caught from doing it again.
(12) A law tends to have a greater preventive effect 
and to be cheaper to administer to the extent it has a strong general deterrence effect.
Prohibitions on driving after drinking more than a speciﬁ  ed 
amount are now in effect in most nations.
(13) In many societies,

(13) In many societies, 
there have also been laws against public drunkenness (being in a public place while intoxicated), and against obnoxious behaviour while intoxicated. Other common prohibitions are concerned with producing or selling alcoholic beverages outside state-regulated channels, and with aspects of drinking under a speciﬁ  ed 
minimum age.
Drinking-driving legislation, such as ‘per se’ laws outlawing driving while at or above a deﬁ  ned blood-alcohol level, has been shown to 
be effective in changing behaviour and reducing rates of alcohol-related problems (Babor et al.,
14 pp. 157–72). The effect is through 
both general and speciﬁ  c deterrence. The quickness and certainty 
of punishment, as well as its severity, are important in the deterrent value (too much severity tends to undercut its quickness and cer tainty).

of punishment, as well as its severity, are important in the deterrent value (too much severity tends to undercut its quickness and cer tainty). 
Drinking driving is an ideal area for applying general deterrence, since the gains from breaking the law are limited, and automobile drivers typically have something to lose by being caught.
Many English-speaking and Scandinavian countries have had a 
tradition of criminalizing drinking in public places or public drunkenness as such, but the trend has been to decriminalize pub-lic drunkenness. Though there are few speciﬁ  c studies, criminaliz-
ing public drunkenness is not very effective in changing behaviour, particularly of those who have little to lose (Parliament of Victoria, Drugs and Crime Prevention Committee,
15 pp. 309–20).
Providing and encouraging alternative 
activities
Another strategy, in principle involving positive incentives, is to

Another strategy, in principle involving positive incentives, is to 
provide and seek to encourage activities, which are an alternative to drinking or to activities closely associated with drinking. This includes such initiatives as making soft drinks available as an alter-native to alcoholic beverages, providing locations for sociability

469
as an alternative to taverns, and providing and encouraging recre-
ational activities as an alternative to leisure activities involving drinking. Job creation and skill development programmes are other examples.
‘Boredom’ and ‘because there’s nothing else to do’ are certainly among the reasons that are given for drinking by some drinkers. And there are often good reasons of general social policy for pro-viding and encouraging alternative activities. But it has been noted that the problem with alternatives to drinking is that drinking combines so well with so many of them. Soft drinks are indeed an alternative for quenching thirst, but they may also serve as a mixer in an alcoholic drink. Involvement in sports may go along with drinking as well as replace it. The few evaluation studies of provid-ing alternative activities, again from a restricted range of societies, have generally not shown lasting effects on drinking behav-iour,

(16,17) though they undoubtedly often serve a general social 
purpose in broadening opportunities for the disadvantaged.(18)
Insulating use from harm
A major social strategy for reducing alcohol-related problems in many societies has been measures to separate the drinking, and particularly heavy drinking, from potential harm. This separation can be physical (in terms of distance or walls), it can be temporal, or it can be cultural (e.g. deﬁ  ning the drinking occasion as ‘time-
out’ from normal responsibilities). These ‘harm reduction’ strate-
gies, as they are called in the context of illicit drugs, are often 
built into cultural arrangements around drinking, but can also be 
the object of purposive programmes and policies (Moore and 
Gerstein,
19 pp. 100–11).
A variety of modiﬁ  cations of the driving environment affect

Gerstein,
A variety of modiﬁ  cations of the driving environment affect 
casualties associated with drinking and driving, along with other casualties. These include mandatory use of seat belts, airbags, and improvements in the safety of road vehicles and roads. Many other practical measures tending to separate intoxication episodes from casualties and other adverse consequences have been put into practice, though usually without formal evaluation.
The main focus for self-conscious strategies of alcohol harm 
reduction in recent years has been on modifying the drinking environment, particularly in public drinking places, primarily by modifying the behaviour of alcohol servers through server training and enforcement of bans on serving those under age or already intoxicated (Babor et al.,
14 pp. 141–47).
Drinking-driving countermeasures are a prime example of an

Drinking-driving countermeasures are a prime example of an 
approach in terms of insulating drinking behaviour from harm, since they seek to reduce alcohol-related trafﬁ  c casualties without 
necessarily stopping or reducing alcohol use. There is substantial evi-dence of the success of a range of such countermeasures (Baboret al .,
14 pp. 159–68). Environmental measures which reduce road
casualties in general—e.g. requiring wearing of seat belts in cars,providing sidewalks separated from the road—may prevent casual-ties associated with intoxication at least as much as other casualties. 
While there is also evidence for the effectiveness of some other harm reduction approaches, there are also many examples of well-meaning efforts which proved ineffective (Room et al.,
2 pp. 186–92).Regulating the availability and conditions 
of use
In terms of the substantial harms to health and public order they

of use
In terms of the substantial harms to health and public order they 
can cause, alcoholic beverages are not ordinary commodities. Governments have thus often actively intervened in the markets for such beverages, far beyond usual levels of state intervention in markets for commodities.
T otal prohibition can be viewed as an extreme form of regulation 
of the market. In this circumstance, where no one is licensed to sell alcohol, the state has no formal control over the conditions of the sales, which nevertheless occur, and there are no legal sales interests, controlled through licensing, to cooperate with the state in the market’s regulation.
With a general prohibition, typically the consumption of alcohol 
does fall in the population, and there are declines also in the rates of the direct consequences of drinking such as cirrhosis or alcohol-related mental disorders.
(19,20) But prohibition also brings with it

(19,20) But prohibition also brings with it 
characteristic negative consequences, including the emergence and growth of an illicit market, and the crime associated with this. Partly for this reason, prohibition is not now a live option in any developed society, although it is in some other societies.
The features of alcohol control regimes, regulating the legal

market in alcohol, vary greatly. Special taxes on alcohol are very common, imposed often as much for revenue as for public health considerations. Many societies have minimum age limits forbid-ding sales to underage customers, and regulating forbidding sales to the already intoxicated. Often the regulations include limiting the number of sales outlets, restricting hours and days of sale, and limiting sales to special stores or drinking places. Rationing of alcohol purchases—limiting the amount individuals can buy in a given time-period—has also been used as a means of regulating availability. Regulations restricting or forbidding advertising of alcoholic beverages attempt to limit or channel efforts by private interests to increase demand for particular alcoholic beverage products. Such regulations potentially complement education and persuasion efforts. State monopolization of sales of some or all alcoholic beverages at the retail and/or wholesale level has also been commonly been

regulations potentially complement education and persuasion efforts. State monopolization of sales of some or all alcoholic beverages at the retail and/or wholesale level has also been commonly been used as a mechanism to minimize alcohol-related harm.

(21)
The effectiveness of speciﬁ  c types of regulation of 
availability
The last 25 years have seen the development of a burgeoning litera-
ture on the effects of alcohol control measures. Speciﬁ  c types of 
regulation of the alcohol market, and the evidence on their effec-tiveness, are discussed below.
(a) Minimum age limits
A minimum age limit is a partial prohibition, applied to one seg-ment of the population. There is a strong evaluation literature showing the effectiveness of establishing and enforcing minimum age limits in reducing alcohol-related problems (Babor et al .,
14
pp. 127–28). However, this literature has been primarily North 
America based, focuses mostly on youthful driving casualties, and mostly evaluates reduction from and increases to age 21 as the limit, a higher minimum age limit than in most societies. The applicability of the literature’s ﬁ  ndings in other societies and where

youth cultures are less automobile-focused has been little tested.4.2.2.6 prevention of alcohol-related problems

SECTION 4  clinical syndromes of adult psychiatry 470
(b) Taxes and other price increases
Generally, consumers show some response to the price of alcoholic 
beverages, as of all other commodities. If the price goes up, the drinker will drink less; data from developed societies suggests this is at least as true of the heavy drinker as of the occasional drinker (Babor et al .,
14 pp. 110–11). Studies have found that alcohol tax 
increases reduce the rates of trafﬁ  c casualties, of cirrhosis mortality, 
and of incidents of violence.(22,23)
(c) Limiting sales outlets, and hours and conditions of sale
There is a substantial literature showing that levels and patterns
of alcohol consumption, and rates of alcohol-related casualtiesand other problems, are inﬂ  uenced by such sales restrictions,
which typically make the purchase of alcoholic beveragesslightly inconvenient, or inﬂ  uence the setting of and after drinking 
(Babor et al .,
14 pp. 125–42). Enforcing rules inﬂ  uencing ‘house

14 pp. 125–42). Enforcing rules inﬂ  uencing ‘house 
policies’ in drinking places on not serving intoxicated customers, etc., has also been shown to have some effect (Babor et al .,
14
pp. 142–45).
(d) Monopolizing production or sale
Studies of the effects of privatizing retail alcohol monopolies have 
often shown some increase in levels of alcohol consumption and problems, in part because the number of outlets and hours of sale typically increase with privatization.
(24) From a public health 
perspective, it is the retail level which is important, while monopo-lization of the production or wholesale level may facilitate revenue collection and effective control of the market.
(e) Rationing sales
Rationing the amount of alcohol sold to an individual potentially

Rationing the amount of alcohol sold to an individual potentially 
directly impacts on heavy drinkers, and has been shown to reduce levels both of intoxication-related problems such as violence, and of drinking-history-related problems such as cirrhosis mortality.
(25,26) But while a form of rationing—the medical prescrip-
tion system—is well accepted in most societies for psychoactive medications, it has proved politically unacceptable nowadays for alcoholic beverages in developed societies.
(f) Advertising and promotion restrictions
Many societies have regulations on advertising and other promo-
tion of sales of alcoholic beverages.(13) As noted, the evidence on 
the effects of advertising and promotion on overall demand has become stronger in the recent literature.
(27) However, studies of 
the effects of advertising and promotion restrictions on alcohol consumption have so far found at best weak effects, at least in the short term (Babor et al.,
14 pp. 180–83).

Social and religious movements and 
community action
Substantial reductions in alcohol-related problems have often been 
the result of spontaneous social and religious movements, which put a major emphasis on quitting intoxication or drinking. In recent decades, there have also been efforts to form partnerships between state organizations and nongovernmental groups to work on alco-hol problems, often at the level of the local community. There has been an active tradition of community action projects on alcohol problems, often using a range of prevention strategies.
(28–31) School-
based prevention efforts have also moved increasingly to try to involve the community, in line with general perceptions that such 
multifaceted strategies will be more effective.(32)

While some of the biggest historical reductions in alcohol prob-
lems rates have resulted from spontaneous and autonomous social 
or religious movements, support or collaboration from a govern-ment can easily be perceived as ofﬁ  cial cooptation or manipula-
tion.
(33) Thus there is considerable question about the extent to 
which such movements can or should become an instrument of government prevention policies.
In the short term, movements of religious or cultural revival can be highly effective in reducing levels of drinking and of alcohol-related problems. Alcohol consumption in the United States fell by about one-half in the ﬁ  rst ﬂ  ush of temperance enthusiasm in 
1830–1845 (Moore and Gerstein,
19 p. 35). Rates of serious crime

19 p. 35). Rates of serious crime 
are reported to have fallen for a while to a fraction of their previous level in Ireland in the wake of Father Mathew’s temperance crusade.
(34) The enthusiasm which sustains such movements tends 
to decay over time, though they often leave behind new customs and institutions with much longer duration. For instance, though the days when the historic temperance movement in English-speaking societies was strong are long gone, the movement had the long-lasting effect of largely removing drinking from the workplace in these societies.
There are some good examples of well-evaluated community 
action projects with demonstrated effectiveness.
(30,31)  However, the 
strategies used in such projects should be guided by evidence on effectiveness; good intentions and effort in themselves offer no guarantee of effectiveness.
Treatment and other help
Providing effective treatment or other help for drinkers who ﬁ  nd

Providing effective treatment or other help for drinkers who ﬁ  nd 
they cannot control their drinking can be regarded as an obligation of a just and humane society. The help can take several forms: a speciﬁ  c treatment system for alcohol problems, professional help 
in general health or welfare systems, or non-professional assistance in mutual-help movements. T o the extent such help is effective, and it is also potentially a means of reducing rates of alcohol-related problems.
Treatments for alcohol problems need not be complex or 
expensive. The evaluation literature suggests that brief outpatient interventions aimed at changing cognitions and behaviour around drinking are as effective in most circumstances as longer and more intensive treatment.
(35,36)  Positive results from such interventions 
in a primary health care settings were shown in a WHO study including a number of countries.
(37)

(37)
In terms of the effects of treatment on those who come for it, there is good evidence of effectiveness of treatment for alcohol problem. Typically, the improvement rate from a single episode of treatment is about 20 per cent higher than the no-treatment condition. Further treatment episodes are often needed. Brief treatment interventions or mutual-help approaches usually result in net sav-ings in social and health costs associated with the heavy drinker (at least where health care is not self-paid), as well as improving the quality of life.
(38,39) However, evaluations of brief interventions

471
by medical general practitioners have not always found effects.(40)
Getting general practitioners to use the methods on a sustained 
basis has not proved easy,(41) and their patients are often unrecep-
tive(42) or recalcitrant.(43) It remains to be seen whether and in 
what sociocultural circumstances making brief interventions for 
problematic drinking a routine part of general medical practice is a feasible and effective strategy.
The effectiveness of providing treatment as a strategy for reduc-
ing rates of alcohol problems in a society is more equivocal. In a North American context, it has been argued that the steep increase in alcohol problems treatment provision and mutual-help group membership in recent decades has contributed to reducing alcohol problems rates.
(44) But the strength of the evidence for this conten-
tion is disputed.(45,46)  A treatment system for alcohol problems is

tion is disputed.(45,46)  A treatment system for alcohol problems is 
an important part of an integrated national alcohol policy, but as an instrument of prevention—of reducing societal rates of alcohol problems—it is probably not cost-effective.
Building an integrated societal 
alcohol policy
Often the different strategies for preventing alcohol problems 
appear to be synergistic in their effects.(47) Controls of availability, 
for instance, are more likely to be adopted, continued, and respected when the public has been successfully persuaded of their effects and effectiveness. But strategies can also work at cross-purposes: a prohibition policy, for instance, makes it difﬁ  cult to pursue meas-
ures which insulate drinking from harm.
In a society where alcohol is a regular item of consumption, in

In a society where alcohol is a regular item of consumption, in 
view of the resulting rates of alcohol-related social and health prob-lems, there is a strong justiﬁ  cation for adopting a comprehensive 
policy concerning alcohol, taking into account production, marketing and consumption, and the prevention and treatment of alcohol-related problems. But while the adoption of overall alcohol strategies or policies has become common,
(48) governments often 
tend to shy away from the most effective strategies.
In terms of strategies we have reviewed for managing and reduc-

ing the rates of alcohol problems in the society, there is clear evidence for effectiveness and cost-effectiveness of measures regu-lating the availability and conditions of use, and some such evidence for some measures which insulate use from harm. With respect to some aspects of alcohol problems, notably drinking-driving, deterrence measures also fall in the same category. The literature has begun to move beyond the question of effectiveness of these measures, and to consider questions of the relative cost-effectiveness of different measures in different societies.
(49)
Despite their perennial popularity, evidence of the effectiveness

(49)
Despite their perennial popularity, evidence of the effectiveness 
of education/persuasion and treatment strategies in reducing soci-etal rates of problems is limited at best. Education and treatment are good things for a society and a government to be doing about alcohol problems, but they do not constitute in themselves a public health policy on alcohol. These strategies will be nevertheless be pursued in most societies, and they can best pursued with attention to using cost-effective methods, and to integrating targets and mes-sages with other aspects of alcohol policy.
Physicians and other health workers observe the adverse effects 
of alcohol in their daily practice, and are well-positioned to argue for public health approaches to reducing the burden of alcohol problems. Reports by colleges of psychiatrists and other physicians have played an important role in such countries as Britain
(50) and 
Sweden(51) in putting a public health response to alcohol problems

(50) and 
Sweden(51) in putting a public health response to alcohol problems 
on the societal agenda.
References 2, 13, and 14 are useful also as sources of more general 
information.
Chikritzhs, T., Gray, D., Lyons, Z., et al. (2007). Restrictions on the sale 
and supply of alcohol: evidence and outcomes. National Drug Research Institute, Curtin University of Technology, Perth,  http://www.ndri.curtin.
edu.au/pdfs/publications/R207.pdf
WHO Expert Committee on Problems Related to Alcohol Consumption. 
(2007). Second report . WHO T echnical Report Series, No. 944, http://
www.who.int/substance_abuse/activities/expert_comm_alcohol_2nd_
report.pdf
 1. Rehm, J., Room, R., Monteiro, M., et al. (2004). Alcohol use. 
In Comparative quantiﬁ  cation of health risks. Global and regional burden 
of disease attributable to selected major risk factors , Vol. 1 (eds. M. Ezzati,

of disease attributable to selected major risk factors , Vol. 1 (eds. M. Ezzati, 
A.D. Lopez, A. Rodgers, and C.J.L. Murray), pp. 959–1108. World Health Organization, Geneva.
 2. Room, R., Jernigan, D., Carlini-Marlatt, B., et al. (2002). Alcohol 
and developing societies: A public health approach . World Health 
Organization, Finnish Foundation for Alcohol Studies & Geneva, Helsinki.
 3. Room, R., Babor, T., and Rehm, J. (2005). Alcohol and public health: a 
review. Lancet ,365, 519–30.
 4. Stockwell, T., Hawks, D., Lang, E., et al. (1996). Unravelling the 
preventive paradox. Drug and Alcohol Review ,15, 7–16.
 5. Bondy, S., Rehm, J., Ashley, M.J., et al. (1999). Low-risk drinking 
guidelines: the scientiﬁ  c evidence. Canadian Journal of Public Health ,
90, 272–6.
 6. Botvin, G.J. (1995). Principles of prevention. In Handbook on drug

90, 272–6.
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4.2.3 Other substance 
use disorders
Contents
buprenorphine

4.2.3.2 Disorders relating to the use of 
 4.2.3.4 Misuse of benzodiazepines
ecstasy and other ‘party drugs’

473
4.2.3.1 Opioids: heroin, methadone, 
and buprenorphine
Opium is derived from the seed of the opium poppy (Papaver som-
niferum) and has been used for thousands of years for its analgesic and euphoriant effects.
What are opioids?
Opioids are drugs which mimic endogenous opioid peptides (e.g. endorphins and enkephalins) and activate opioid receptors. Opioids include both naturally occurring opiates extracted from opium (morphine and codeine) and synthetic opioids (heroin and methadone). Heroin is the most common opioid to be misused partly because of its distinctive euphoriant effects.
Neurobiology of opioids
Opioid receptors are widely distributed throughout the central nervous system. Activation of opioid receptors inhibits activity of the dorsal horn. The three most important opioid receptors are μ-receptor, δ-receptor, and κ-receptor. The μ-receptor is concen-

trated in brain areas and is mostly involved in nocioception(pain sensation). μ-receptor and δ-receptor activation cause
hyperpolarization of neurones by activating K + channels involving 
G-proteins. Exogenous opioids such as heroin and methadone act at all opioid receptors but particularly at μ-receptors. Opioidreceptor antagonists such as naloxone reverse the effects of opioid agonists.
(1)
The precise mechanisms of tolerance and dependence to opioids 
are not clear. Short term use of opioids causing intoxicationmay not lead to neuroadaption of opioid receptors. However,continued use of opioids may lead to opioid receptor desensitiza-tion and dependency. Acutely, opioids lead to the inhibition of adenylate cyclase with reduced conversion of ATP to cAMP ,resulting in reduced ﬁ  ring at noradrenergic neurones located on

the locus coeruleus. Chronic opioid administration leads tocompensatory upregulation of cAMP , returning levels towards baseline. On cessation of opioid use (or following opioid receptor antagonism), withdrawal ensues, characterized by a massive surge in unopposed noradrenergic activity (termed the ‘noradrenergic storm’) from the locus coeruleus. This noradrenergic hyperactivity is thought to underlie many symptoms of opioid withdrawal,
and explains some of the efﬁ  cacy of the presynaptic α2 agonists
in the treatment of the symptoms of acute opioid withdrawal. Opioid receptors can readapt back to normal in the absenceof opioids.
(2)Both glutamate and γ-aminobutyric acid (GABA) are also likely

(2)Both glutamate and γ-aminobutyric acid (GABA) are also likely 
to be involved. Positive reinforcement is thought to be mediated via the dopaminergic mesolimbic system. In the ventral tegmental area, GABA inhibits dopaminergic neurones, which in turn are inhibited via μ-opioid receptor activation. Consequently, opioid use leads to increased dopaminergic activity which is thought to mediate the drive to use and its positive reinforcement.
Route of administration
Heroin may be administered by a number of routes including injecting (intravenous, intramuscular and subcutaneous ‘skin popping’), snorting and ‘chasing the dragon’ (inhaling after heating on tin foil).
(3) These different routes of administration have

(3) These different routes of administration have 
profound effects on bioavailability, speed of onset, severity of dependence and physical complications. Different types of heroin may be preferentially used by different routes of administration.
(4)
Brown heroin is poorly water soluble with a high oil content which ‘runs’ well on a heated foil making it better for ‘chasing’ . In contrast, white heroin tends to be more water soluble and better suited for intravenous use, although it may still be snorted or smoked after preparation.
Whilst smoking heroin (‘chasing the dragon’) is probably the 
most commonly used route of self-administration, it is not as effec-tive or efﬁ  cient as injecting. Consequently, as heroin users develop

most commonly used route of self-administration, it is not as effec-tive or efﬁ  cient as injecting. Consequently, as heroin users develop 
tolerance, many subsequently change to the intravenous route. Injecting heroin use is also associated with a greater risk of fatal overdose and hence reducing the transition from smoking to inject-ing may be associated with reduced harms. Although injecting in the upper limbs is the most common site for administration, 
as venous access becomes compromised increasingly risky sites such as the groin or neck my be used. However, non-injecting routes of administration are not without risks and may still result in dependence and similar treatment outcomes.
Opioid metabolism
The oral bioavailability of heroin (Diacetylmorphine) itself is poor due to complete ﬁ  rst pass metabolism, which is the reason it is

The oral bioavailability of heroin (Diacetylmorphine) itself is poor due to complete ﬁ  rst pass metabolism, which is the reason it is 
often administered by alternative routes. Following administration, heroin is rapidly metabolized to 6-monoacetylmorphine (6-MAM), which is the only metabolite that speciﬁ  cally indicates that heroin 
has been used. 6-MAM is metabolized to morphine, which is catalyzed in the liver. Morphine (either as a metabolite of heroin or given as a drug) is mostly metabolized by UDP-glucuronosyltrans-ferase (UGT) to the inactive metabolite morphine-3-glucuronide (M3G) and in lesser amounts to the active morphine-6-glucuronide (M6G). Morphine is also 
N-demethylated to normorphine by 
hepatic CYP3A4 and CYP2C8 enzymes (Fig. 4.2.3.1.1). Heroin and its metabolites can be monitored in the blood, hair, saliva and urine. 6-MAM is detectable up to 12 h post administration, whilst morphine can be detected in the urine for several days after use.
(5)

(5)
Methadone is primarily metabolized in the liver by CYP3A4 to the inactive metabolite 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrro-lidine (EDDP), then to 2-ethyl-5-methyl-3,3-diphenylpyraline (EMDP). Buprenorphine is metabolized to norbuprenorphine and to conjugated buprenorphine and norbuprenorphine.Codeine (3-methylmorphine) is synthesized from morphine and metabolized to codeine-6-glucuronide. Additionally codeine is  4.2.3.6 Disorders relating to the use of volatile substances
Wayne Hall
 4.2.3.8 Nicotine dependence and treatment
Ma Inés López-Ibor4.2.3.1 opioids: heroin, methadone, and buprenorphine

SECTION 4  clinical syndromes of adult psychiatry 474
metabolized to morphine by CYP2D6. Therefore a morphine posi-
tive result is possible after consuming codeine only.(5)
Dihydrocodeine is metabolized to nordihydrocodeine and dihy-dromorphine and cannot normally be metabolized to codeine or morphine.
The illicit nature of opioid use means that it is often difﬁ  cult to 
estimate the exact prevalence. The European Monitoring Centre for Drugs and Drug Addiction reports that heroin use in the general population is less than one per cent.
(6) Gender differences in opioid 
use have been reported with women accounting for approximately one third of all opioid users. Non-dependent recreational heroin use has been reported, but is rare. Dependence will often develop gradually over the ﬁ  rst few years, most commonly in the late teens

and early twenties. Treatment can alter the course of opioid depen-dence, by prolonging periods of abstinence and improving out-comes (see later sections). The risk of death from heroin depen-dence is approximately 12 times that of the general population, with most deaths occurring in males ( > 80 per cent). Opioid use has a 
major effect on crime and it has been estimated that half of all crime is drug related, with estimated costs within the UK criminal justice system at £1 billion per annum in 1996.
The effects of opioids
The effects of opioids are outlined in Table 4.2.3.2.1. The effects vary depending on dose and route.
Opioid dependence and withdrawal
Opioid dependence may be classiﬁ  ed according to the ICD-10

Opioid dependence may be classiﬁ  ed according to the ICD-10 
criteria (see appendix). Continued use of heroin (or other opioids) tends to lead to physiological dependence with the development of tolerance and withdrawal symptoms on discontinuing heroin. T olerance occurs when the same dose gives a reduced effect or con-versely, an increased opioid dose is required to have the same effect. Once physiological dependence is established, abrupt cessation or a marked reduction in dose will result in a withdrawal syndrome. 
During this time there is an ‘undoing’ of the neuroadaptation which had occurred during the development of tolerance. Withdrawal leads to ‘gooseﬂ  esh’ (piloerection) of the skin (which is

During this time there is an ‘undoing’ of the neuroadaptation which had occurred during the development of tolerance. Withdrawal leads to ‘gooseﬂ  esh’ (piloerection) of the skin (which is 
the reason behind the term ‘cold turkey’). Insomnia (with increase in Rapid Eye Movement sleep) and craving for the drug may persist for weeks. Most withdrawal symptoms appear within 4–12 h and peak at 48–72 h lasting 7–10 days. Longer acting opioids such as methadone may result in a more prolonged withdrawal. Opioid withdrawal is not usually considered to be life threatening.
Complications from opioid use
Complications may be biological, psychological, or social (Table 4.2.3.1.2).
Biological complications
Opioid overdose is the most common cause of death among opioid users, while blood-borne virus infection and other injecting related complications also contribute to increased morbidity and prema-ture deaths.
(a) Opioid overdose

Opioid overdose occurs when the opioid dose exceeds the individ-ual’s tolerance to the respiratory depressant effect of the drug.HeroinO
O
O
O
O
OOO
OHOH OH
NO
OOCOOH
OH
OHHOOH
HNOOH
OHCOOH
HOOH
OH
OHN
NO
O
O
ON
NPseudo-ChE
Pseudo-ChE6-Monoacetylmorphine
UGT1A1
UGT1A3UGT1A6UGT1A8UGT1A9UGT1A10UGT2B7Morphine
CYP3A4
CYP2C8UGT2B7
Morphine-3-Glucuronide Normorphine Morphine-6-GlucuronidehCE1
hCE2
hCE1
hCE2
Fig. 4.2.3.1.1 Major metabolic 
pathways of heroin and morphine in humans.
(6) Reproduced from Maurer, 
H.H., Sauer, C., Theobald, D.S. (2006). Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism 
of tetrahydrocannabinol, cocaine, 
heroin, morphine, and codeine. The Drug Monit. 2006 June; 28(3), 447–53, 
copyright 2006, Lippincott Williams & Wilkins
Table 4.2.3.1.1 Effects of opioids
Mood change (euphoria)
Analgesia
Drowsiness/Sleep
Respiratory depressionCough reﬂ  ex depression

Analgesia
Sensitization of the labyrinth with nausea and vomiting
Decreased sympathetic outﬂ  ow (bradycardia and hypotension)
Lowering of the body temperature
Pupillary constriction
Constipation

475
It is more common when other Central Nervous System depres-
sants are concurrently consumed. Respiratory depression iscaused by the opioid action on the brain stem nuclei and death can follow within minutes of injecting excessive amounts. Risk factors for opioid overdose are injecting use, return to opioid use follow-ing recent abstinence (such as following detoxification andrelease from prison), during the early stages of dependence and starting opioid substitution treatment.
(7) In addition, variability
in opioid purity, increased central depressant effects following polysubstance use and high levels of psychiatric co-morbiditymay increase the vulnerability for accidental or intentionaloverdose. Opioid overdose can be rapidly reversed if naloxone (opioid antagonist) is administered to the person who has over-dosed. The management of an opioid overdose is described later in the chapter.
(b) Blood borne virus transmission

The risk of viral transmission is high among injecting drug users,and routine testing with counseling should be available to thoseat risk. Tr ansmission of blood borne viruses is primarily related
to sharing injecting equipment and involvement in the sex indus-try. Needle sharing appears to occur less frequently than sharingof spoons and ﬁ  lters, but any shared equipment may pose the risk 
of viral transmission. The prison population is particularly at risk, as injecting is more common likely to involve sharing injecting equipment.
Opioid substitution treatment is one of the most effective inter-
ventions for reducing the extent of injecting, thereby also reducing both the spread of and morbidity from blood borne viruses. Stabilization on methadone/buprenoprehine with abstinence from injecting, needle and other injecting equipment sharing, and 
unprotected sex should be encouraged among all dependent heroin

unprotected sex should be encouraged among all dependent heroin 
users. Blood borne virus testing and referral to specialists for treatment is important. In addition, close liaison with medical and psychiatric services is important for improving outcomes and compliance with treatment.
(i) Human immunodeﬁ  ciency virus (HIV)
Rates of HIV seropositivity amongst current injecting drug users 
in England and Wales although low, have recently increased, with 
an incidence of 1.5 per cent reported in 2004 (the highest since 
1992), with higher rates reported in London.(8) The relatively low 
levels of HIV within the UK and elsewhere in Europe is believed to be due to the widespread availability of ‘needle-exchange’ services 
and provision of services focused towards ‘harm minimization’ .(9)
(ii) Hepatitis B & C

Screening of drug users in treatment has revealed prevalence rates of 20 per cent for Hepatitis B and more than 50 per cent for Hepatitis C. Intravenous drug users are likely to have higher rates estimated at 30 to 50 per cent (Hepatitis B) and up to 90 per cent (Hepatitis C).
(10) Prognosis is worsened by high levels of alcohol 
consumption and therefore liaison with hepatitis/gastroenterology services is important. Screening for Hepatitis B and C and targeted vaccination for Hepatitis B, in addition to education and harm-reduction provision, should be provided.
Psychological complications
Numerous large epidemiological studies have identified that co-morbid psychiatric illness is common among those with opioid dependence, with prevalence rates of about 50 per cent.
(11)

(11) 
Concurrent use of benzodiazepines, alcohol, and especially stimu-lant drugs increases psychiatric morbidity in addition to female gender, poor physical function, and difﬁ  culties in personal relation-
ships.
(12) Many of those with opioid dependence will have had 
childhood behavioural problems such as conduct disorder which may be a marker for subsequent drug use.
(13) The rate of suicide 
among heroin users is estimated at 14 times that of age matched peers with reports of 3–35 per cent of deaths related to suicide. Risk factors include a history of depression, poly substance use in addition to generic risk factors.
(14)
At entry into treatment, it may be difﬁ  cult to make an accurate

(14)
At entry into treatment, it may be difﬁ  cult to make an accurate 
determination of an opioid user’s psychiatric diagnosis and gener-ally assessment should be repeated once stability on a substitution medication or detoxiﬁ  cation has been achieved. Waiting to review 
a patient’s mental health once they are out of crisis can prevent early misdiagnosis since much of psychiatric distress dissipates rapidly on cessation of illicit use and stabilization. In one follow up study of opioid users entering treatment, baseline levels of depres-sion fell from 25 per cent at baseline to 11 per cent at 12 month follow up, with the observed decline being strongly related to treat-ment exposure.
(15) Follow-up and provision of treatment for

(15) Follow-up and provision of treatment for 
co-morbid disorders are thus essential. Enhancing compliance with prescribed medications through supervised dispensing or engage-ment of carers is useful. Treatment can be effective in reducing psychiatric distress observed on entry to treatment in this group. However, in a signiﬁ  cant proportion, even on cessation of use or 
abstinence, major psyc hiatric illnesses can persist. If left untreated, 
co-morbid conditions can lead to a poorer prognosis particularly in 
respect to relapse and suicide.
Social complications
The ramiﬁ  cations of heroin dependence upon individual func-

tioning and that individual’s ability to relate and function within their family and community are immense. Although high rates of socioeconomic disadvantage often precede entry into heroin use, it is the other associated problems of relatively poorer pre-morbid functional and educational attainment that frequently compound later efforts at rehabilitation. High rates of criminal activity, homelessness, and unemployment are associated with opioid addiction, although treatment can improve socio-economic status.Table 4.2.3.1.2  Complications of opioid use
Biological Psychological Social
– hepatitis and HIV
– bacterial endocarditis– septicaemia
– abscesses
– cellulitis
Cardiorespiratory– pulmonary emboli
– aspiration
– cardiac arrthymias
– respiratory depression

– overdose deathPsychiatric complications
– depression
– suicideCriminal behavior
– fund dependence
Loss of housing
UnemploymentLoss of family
– family breakdown4.2.3.1 opioids: heroin, methadone, and buprenorphine

SECTION 4  clinical syndromes of adult psychiatry 476
Treatment of opioid dependence
Opioid maintenance treatment
Opioid maintenance treatment generally involves substituting 
heroin for an oral long-acting opioid, thereby reducing the plasma level variability and stopping injecting drug use. Oral methadone and buprenorphine have been licensed in several countries for use in the treatment of opioid dependence and both are approved in the UK.
(16) The decision regarding whether methadone or buprenor-
phine is used should be based on individual factors estimating the risks and beneﬁ  ts and following discussion with the patient. If both 
drugs are equally suitable, cost-effectiveness examination by the National Institute of Clinical Excellence (NICE) concludes that methadone should be prescribed as the ﬁ  rst choice.
(16)
(a) Methadone maintenance treatment
Methadone is a synthetic orally active full opioid agonist with

(16)
Methadone is a synthetic orally active full opioid agonist with 
a half-life of 24–36 h, making it suitable for daily administration. This is an effective treatment for heroin dependence and has sig-niﬁ cantly better outcomes than non pharmacological substitution 
for retaining patients in treatment, decreasing heroin use, reducing crimes, reducing overdose deaths, reduced injecting and sharing of injecting equipment and consequent reduced risk behaviours leading to transmission of HIV .
(17) Higher doses of methadone
(60 to 120 mg/day) have been shown to be more effective than lower dosages
(18) and doses greater than 80 mg daily are believed to 
provide a reasonable level of opioid receptor blockade such that euphoria from illicit opioids is diminished.
Methadone steady state plasma levels take approximately 4 to

Methadone steady state plasma levels take approximately 4 to 
5 days and so there is potential for methadone accumulation (and overdose) when initiating treatment. Deaths have been recorded during the induction phase onto methadone especially when the recipient is not as tolerant as believed or is using other opioids or substances.
(19) Therefore, conﬁ  rmation of the patient’s depen-
dent status is paramount as described in the chapter and it is safer to start treatment at low doses (not more than 30 mg daily). Treatment should be initiated under supervision with oral metha-done liquid where consumption can be easily monitored. Doses should generally be increased slowly, and titrated against with-drawal symptoms. As methadone can accumulate, there should be increased observation over the ﬁ  rst few weeks of treatment.

Doses can then gradually be increased to within therapeutic levels (60–120 mg daily). Prescribing should follow the guidelines out-lined later in the chapter.
(b) Buprenorphine maintenance treatment
Buprenorphine (Subutex) is a synthetic partial opioid agonist which is given as a sublingual tablet and has a high afﬁ  nity at 
μ-opioid receptors. It is an effective treatment for use in maintenance treatment for heroin addiction, but is not more effective than methadone at adequate dosages.
(20)
Buprenorphine undergoes extensive ﬁ  rst metabolism. Therefore,

(20)
Buprenorphine undergoes extensive ﬁ  rst metabolism. Therefore, 
it is administered as sublingual tablets (2 mg and 8 mg) with bio-availability of between 30–40 per cent. Optimizing sublingual absorption while minimizing diversion is a practical challenge that supervised dispensing points still need to address. Taking 5–7 min-utes to dissolve, buprenorphine reaches a plateau on most physio-logical subjective effect at a daily dose of 4–16 mg. At higher doses, the duration of action increases, permitting less than daily dosing in about one-third of patients. Because of its high afﬁ  nity for the 
opioid receptor, buprenorphine will precipitate withdrawal if

opioid receptor, buprenorphine will precipitate withdrawal if 
administered to someone with an opioid agonist on board (typically within 8 h of heroin use or 24–36 h of methadone use). Therefore, patients are advised to wait until they are in mild withdrawal before commencing treatment. Finally, it is thought to be safer in overdose (with a ‘ceiling’ in the respiratory depression, unlike with full opi-oid agonists) and so induction can be quite rapid aiming for doses of between 8–16 mg by day 3.
It is an effective analgesic but may be less suitable than metha-

done for those with chronic pain. Although safer in overdose than methadone, fatal overdose can occur especially when taken in com-bination with other substances. As with methadone dose, reduc-tion in someone stable on maintenance should be done gradually (typically 2 mg ever 2 weeks) and only supported when there is evi-dence of continued abstinence from illicit opioid use. Continued dose reduction in the face of return to illicit use is likely to further destabilize the patient. In some countries (e.g. many European countries since 2007), another preparation has become available (Suboxone), in which buprenorphine has been combined with nal-oxone in a ratio of 4:1 to reduce the desirability of injecting diverted medication. When taken as directed (sublingual), the bioavailability of naloxone is very poor, whereas when injected by a dependent opi-ate user, a severe withdrawal reaction may be precipitated.

(c) Other opioid maintenance treatments
Injectable methadone and injectable heroin are rarely prescribed in the United Kingdom and at present there is insufﬁ  cient evidence to 
guide this use.
(21) However, it may be considered in some patients 
as a ‘second-line’ treatment option for whom an adequate trial (e.g. at least 6 months) of optimized methadone maintenance treatment (e.g. doses > 80 mg daily, regular supervised dosing, regular appoint-
ments and appropriate management of medical or psychiatric co-morbidity) is ineffective in controlling illicit injecting heroin use. This should only be initiated by a specialist. Both long-acting morphine and dihyrocodeine have been compared to methadone in two randomized controlled trials which have revealed broadly equivalent outcomes between the groups.
(23,23)
Opioid detoxiﬁ  cation
Detoxiﬁ  cation may be based on suppression of the ‘nor-adrenergic 
storm’ that accompanies opioid withdrawal, by prescribing either

(23,23)
storm’ that accompanies opioid withdrawal, by prescribing either 
α2-receptor agonists or a gradual reduction of an opioid agonist. 
When a patient is stable and motivated, a gradual reduction in the dose of opioid maintenance dose can be an effective means for attaining abstinence. However, it must be noted that detoxiﬁ  cation 
is generally associated with poor long term rates of abstinence and retention in treatment.
(a) Buprenorphine detoxiﬁ  cation
Buprenorphine has been found to be more effective than clonidine 
(below) for the management of opioid withdrawal. In addition, there is no signiﬁ  cant difference between buprenorphine and 
methadone in terms of completion of treatment, but withdrawal symptoms may resolve more quickly with buprenorphine.
(24) This

(24) This 
can be undertaken as an inpatient or outpatient. Buprenorphine should only be taken after cessation of heroin use as it canprecipitate withdrawal. Withdrawal may be achieved by theburpenorphine dose being stabilized according to withdrawal over

477
a 24–48 h period, after which a gradual dose reduction should 
occur over 5–21 days in the inpatient or outpatient setting.
(b) Methadone detoxiﬁ  cation
Methadone detoxification can be used for pharmacologically 
assisted opioid detoxiﬁ  cations. A review revealed that withdrawal 
programs vary widely with regard to duration, design and treatment objectives. This review conﬁ  rmed that slow tapering with tempo-
rary substitution of methadone accompanied by medical supervi-sion and ancillary medications can reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use.
(25)
(c) α2-Agonist assisted detoxiﬁ  cation
α2-agonists, such as lofexidine and clonidine, reduce pre -synaptic
nor adrenaline release alleviating many withdrawal symptoms asso-ciated with opioid withdrawal. The dose is titrated against the symptoms and signs of withdrawal whilst also avoiding hypotensive episodes. Detoxiﬁ  cation can occur in both outpatient and inpatient

settings. Lofexidine that has a lower incidence of hypotension than 
clonidine is the preferred non-opioid method of assisting opioid withdrawal. A review has concluded that there is no signiﬁ  cant dif-
ference in efﬁ  cacy for treatment regimes based on clonidine and 
lofexidine, compared to reducing doses of methadone over a period of around 10 days, for the management of opioid withdrawal.
(26)
(d) Naltrexone assisted detoxiﬁ  cation
Some research has been published suggesting that withdrawal may 
also be completed more quickly by additionally administering the long-acting opioid antagonist naltrexone. However, further research is still needed to conﬁ  rm effectiveness and safety of this treatment.
Naltrexone for relapse prevention
Oral naltrexone has recently been recommended in the UK for 
the management of opioid dependence. Naltrexone is relevant for highly motivated patients who have completed an opioid detoxiﬁ  -

cation. This may be combined with arrangements for supervision and should be given as part of a programme of supportive care. Regular reviews of effectiveness of naltrexone should be undertaken by the clinician and discontinuation of treatment should be considered if there is evidence of continued opiate misuse.
(27)
Psychosocial interventions for opioid dependence

(27)
There are numerous psychosocial approaches that are currently used in the management of substance misuse. Treatment based on a holistic approach encompassing biological, psychological and social aspects of care is likely to improve outcomes. Psychosocial treatments such as relapse prevention, motivational interviewing and contingency management are often used in the addiction set-ting. Cognitive behaviour therapy and other types of psychotherapy are also used particularly for those with a speciﬁ  c psychiatr ic disorder 
such as depression and can be referenced elsewhere in the book.
Relapse Prevention looks at identiﬁ  cation of triggers for craving 
(e.g. people, places, or moods) and uses learning techniques (dis-traction, relaxation) to handle high-risk situations.
(28) Motivational

(28) Motivational 
interviewing techniques can help patients move along a ‘cycle of change’ from pre-contemplation (no interest in changing behav-iour) to contemplator, to determination and action without confrontation.
(29) This is based on ﬁ  ve key pr inciples (Tab le 4.2.3.1.3)
which are often used in both addiction and eating disorders, but may also be used in any aspect of the doctor-patient relationship where the patient is ambivalent about change.
(30) Although used

(30) Although used 
rarely in the UK, Contingency Management (CM) has a stronger evidence base. This behavioural treatment uses rewards or other reinforcers to promote abstinence or other selected goals. Narcotics Anonymous is based on the 12-step program (the philosophy behind Alcoholics Anonymous) where the individual accepts they have a drug problem and uses 12 steps (Table 4.2.3.1.4) within the group setting, to attain abstinence.
(31)
Psychosocial interventions alone have not been shown to be 
more effective than no treatment.(32) However psychosocial inter-
ventions combined with pharmacological interventions have been shown to lead to better outcomes.
(33)
Educating the drug user about safe practices (including safer

(33)
Educating the drug user about safe practices (including safer 
injecting, not sharing equipment) and harm-reduction techniques is important, as is appropriate liaison with other agencies such as social services or voluntary sector supports. Therapeutic commu-nities, residential rehabilitation and ‘concept houses’ based on a religious or abstinent theme offer longer-term care.
Management of opioid dependence
The treatment plan should be made jointly between the clinician and patient. The actual management plan depends on whether the person has opioid dependence, the amount of opioids used, and the outcome of the mutually agreed treatment objectives and4.2.3.1 opioids: heroin, methadone, and buprenorphine
Table 4.2.3.1.3  Principles of motivational interviewing(30)
X express empathy
X help the client to see discrepancies in their behaviours
X avoid argument
X roll with resistance

X support the patient’s sense of self-efﬁ  cacy.
Reproduced from Miller, W. and Rollnick, S. Motivational Interviewing, copyright 1991, 
Guildford Press NY .
Table 4.2.3.1.4  12 Steps of Narcotics Anonymous(31)
 1.  We admitted that we were powerless over our addiction, that our lives 
had become unmanageable.
 2.  We came to believe that a Power greater than ourselves could restore us 
to sanity.
 3.  We made a decision to turn our will and our lives over to the care of 
God as we understood Him.
 4. We made a searching and fearless moral inventory of ourselves. 5.  We admitted to God, to ourselves, and to another human being the exact 
nature of our wrongs.
 6.  We were entirely ready to have God remove all these defects of character.
 7. We humbly asked Him to remove our shortcomings.

 8.  We made a list of all persons we had harmed, and became willing to make 
amends to them all.
 9.  We made direct amends to such people wherever possible, except when 
to do so would injure them or others.
10.  We continued to take personal inventory and when we were wrong 
promptly admitted it.
11.  We sought through prayer and meditation to improve our conscious 
contact with God as we understood Him, praying only for knowledge of 
His will for us and the power to carry that out.
12.  Having had a spiritual awakening as a result of these steps, we tried to carry 
this message to addicts, and to practice these principles in all our affairs.
Reprinted by permission of NA World Services, Inc. All rights reserved.

SECTION 4  clinical syndromes of adult psychiatry 478
treatment plan. Opioid dependence management is sometimes 
based on ‘abstinence’ , where the person refrains from taking drugs, but also needs to be based on the principles of harm reduction. Harm reduction aims to reduce harms from opioid use often in terms of reducing deaths, spread of blood-borne viruses or improv-ing psychosocial outcomes. This may optimally be achieved through cessation of injecting illicit opioid use by stabilizing the person on an opioid replacement.
Assessment of opioid use and dependence
A comprehensive assessment of opioid use patterns and associated risks forms the basis of any treatment plan. A suggested plan of enquiry that allows both accurate diagnosis and risk assessment is outlined below.
(a) Clinical assessment
1Current consumption:  How much heroin (or other opioid) is 
consumed on a typical day, in terms of either weight or money spent, and for how long has consumption been at this level? Are

consumed on a typical day, in terms of either weight or money spent, and for how long has consumption been at this level? Are 
opioids taken daily? What happens when no opioids are taken? The route of use (smoking, intravenous injection), number of adminis-trations per day, and the minimum amount of opioid required each day to avoid withdrawal symptoms should also be assessed. Enquiry should be made to determine if more than one type of opioid is being used (e.g. prescribed medication or street metha-done). All other substances being used should be identified(e.g. cocaine, benzodiazepines and alcohol) and their patterns of use.
2Typical day:  A systematic enquiry of the person’s typical day and

2Typical day:  A systematic enquiry of the person’s typical day and 
the use of opioids and other substances is particularly important for assessing evidence of withdrawal. This can also be useful for identifying risk activities that the user engages in to support their ongoing use, including criminal activity, high risk sex, or inject-ing practices.
3Drug use history:  A careful enquiry needs to be made to deter-
mine the temporal relationship between the onset of drug use and any psychological behaviors. The age of ﬁ  rst use and the psychoso-
cial precipitants of use should be established, as should the devel-opment of tolerance and craving through increased frequency of use, escalating dose, and where relevant, the onset of injecting.
4Biopsychosocial complications:  This should assess episodes of

4Biopsychosocial complications:  This should assess episodes of 
overdose (intentional or accidental), viral screening status and injecting behaviour including use of needle exchanges, sharing equipment and use of high-risk injection sites such as the groin and neck. Effects on family relationships, employment and crim-inal activity, and co-morbid psychiatric conditions related to opioid use should be assessed.
5Past treatments and abstinent periods:  Have they ever been in 
contact with treatment services, maintained on substitute medi-cation or undertaken a detoxiﬁ  cation? What was their longest 
period of abstinence? What has helped in the past? When and why did relapses occur? What are high-risk situations and other triggers for use?
6Motivation for change:  Why seek treatment now? What support 
is needed? Thinking of Livelihood (ﬁ  nancial), Life (physical 
health), Love life, Legal problems and Losing it (loss of control)

health), Love life, Legal problems and Losing it (loss of control) 
can be helpful as these are often precipitants for seeking treat-ment and can be used to encourage behavioural change.(b) Conﬁ  rmation of dependence
Although a diagnosis of opioid dependence can be made by taking a 
full history; dependence and tolerance to opioids should be corrobo-rated before commencing substitute treatment. Conﬁ  rmation of 
dependence and tolerance prior to commencing treatment is impor-
tant since the greatest risk associated with prescribing methadone is

tant since the greatest risk associated with prescribing methadone is 
the possibility of overdose following consumption of methadone by a non-tolerant individual. Corroborative information may come from urine drug screens and other health care practitioners such as the GP or criminal justice worker. Physical examination is essential and may reveal stigmata of injecting drug use such as evidence of recent intravenous injection sites or the more long-term ‘track marks’ (linear scarring along veins from repeated intravenous use) on the 
drug user’s limbs. All patients should be asked where they usually 
inject and recent injection sites should be examined. In those with poor upper limb veins, with evidence suggestive of ongoing illicit use, it may be appropriate to examine groin or neck sites.
Urines tests are supportive of use but not conﬁ  rmatory of depen-

dence. Sequential urine testing over a few days may allow theconﬁ  rmation of regular opioid (although not necessarily heroin) 
consumption. Measurement of withdrawal by using withdrawal scales (Table 4.2.3.1.5) in addition to examining for presence of tachycardia and hypertension, following a period of abstinence, is helpful in conﬁ  rming withdrawal. The Objective Opiate Withdrawal 
Scale (Table 4.2.3.1.5) is useful when assessing whether a person is in withdrawal before commencing opioid substitution treatment and useful after commencing treatment to aid assessing whether the opioid substitute dose is adequate. Partial or full reversal of with-drawal following a measured dose of opioids administered on site will provide some information of the patient’s level of tolerance.
Table 4.2.3.1.5  Objective opiate withdrawal scale
(27)
This is to be completed by clinician. A score should be given for each observation

(27)
This is to be completed by clinician. A score should be given for each observation 
within a 5 minute observation period.
Observations Scoring
1. Yawning 0 = no yawns 1 = ≥ 1 yawns
2. Rhinorrhoea 0 = <3 sniffs 1 = ≥3 sniffs
3.  Piloerection (observe arm) 
‘gooseﬂ  esh’0 = absent 1 = present
4. Perspiration 0 = absent 1 = present
5. Lacrimation 0 = absent 1 = present
6. Tremor 0 = absent 1 = present
7. Mydriasis 0 = absent 1 = ≥ 3mm
8. Hot and cold ﬂ  ushes 0 = absent 1 = shivering / huddling for warmth
9. Restlessness 0 = absent 1 = frequent shifts of position
10. Vomiting 0 = absent 1 = present
11. Muscle twitches 0 = absent 1 = present
12. Abdominal cramps 0 = absent 1 = Holding stomach
13. Anxiety 0 = absent 1 = mild – severe
TOTAL SCORE
National Institute for Health and Clinical Excellence (NICE) (2005) TA115 Drug 
misuse–naltrexone. London: NICE. Available from www.nice.org.uk/ TA115 Reproduced with permission.

479
Investigations for patients with opioid dependence
Heroin dependence is associated with high rates of physical and 
psychiatric morbidity. Since access to primary health care may be difﬁ cult, basic physical health checks should be a fundamental part 
of all drug treatment. The core assessment should include history, physical examination, routine blood tests, blood borne virus screening and vaccination where appropriate, and assessment of nutritional status, mental and dental health. Referral to appropri-ate specialist services should be facilitated through coordinated 
care planning which should form the cornerstone of structured 
drug treatment delivery.
Management options for opioid dependence
Following a careful and thorough assessment which allows conﬁ  rmation of dependence as outlined above, there are several

Following a careful and thorough assessment which allows conﬁ  rmation of dependence as outlined above, there are several 
treatment options. In the short term, opioid substitution treatments with methadone or buprenorphine may be offered. Opioid substi-tution treatment should be monitored closely, especially during the initial phase of treatment. Initiation of opioid substitution treat-ment usually takes place in the community setting, but may occur in an inpatient setting if there is a complicated history involving medical or psychiatric morbidity. Opioid maintenance treatment is continued in the community setting and can be continued as main-tenance for the long term, with some patients continuing treatment for over 50 years. Treatment for opioid dependence is likely to be improved when framed within a comprehensive treatment package including psychosocial and pharmacological interventions.
(32)

(32)
Relapse prevention and motivational interviewing can be carried out during regular appointments with health professionals. Community substance misuse teams often use keyworking as a model of care for opioid dependent patients. This is where one healthcare professional looks after the patients care and provides the main source of contact, often following up referrals and ensur-ing medical and psychosocial needs are met. Opioid maintenance treatment within the community substance team may continuein the long term or be a prelude to starting abstinence basedtreatments, with the aim of stopping all illicit heroin use.
Abstinence can be achieved by pharmacologically assisted with-
drawal from the opioid via a detoxiﬁ  cation with either lofexidine or 
an opioid substitute such as methadone or buprenorphine (as above). This usually takes 10–21 days but may be longer if withdrawal from 
a longer acting opioid is required. Opioid detoxiﬁ  cation may take

a longer acting opioid is required. Opioid detoxiﬁ  cation may take 
place in the inpatient or community setting, depending on the level of medical and psychiatric morbidity. Following opioid detoxiﬁ  ca-
tion patients may beneﬁ  t from treatment within a therapeutic 
community or residential rehabilitation centre where life skills for dealing with a world without opioids may be developed. For patients who do not enter rehabilitation centres, regular sessions with keyworkers using relapse prevention and motivational inter-viewing may also be beneﬁ  cial. Highly motivated patients may also 
beneﬁ  t from naltrexone to prevent relapse (described above).
Prescribing opioids for opioid dependence
In the United Kingdom, all doctors may prescribe methadone

In the United Kingdom, all doctors may prescribe methadone 
or buprenorphine for the treatment of dependence, although prescribing should generally be initiated by a specialist or special interest general practitioner. Prescriptions for opioid dependence should ideally be dispensed daily with supervised doses, particularly for the ﬁ  rst three months of treatment. After about three months,
if a patient is stable (based on psychosocial outcomes and illicit substance use) the number of dispensings per week and level of supervision may be reduced, although this may be varied when there are extenuating circumstances. UK guidelines advocate that no more than a week’s medication is dispensed at a time.
Liaison between the pharmacist, the general practitioner and 
the specialist is important to prevent double scripting, reduce

the specialist is important to prevent double scripting, reduce 
diversion and improve safety. Clinicians in all specialties should 
be aware of the potential for all opioid-containing analgesics to be diverted for abuse or develop into iatrogenic dependence. Repeat prescriptions of such analgesics should be carefully reviewed. Prescriptions for controlled drugs can only be for 28 days in total and the total prescribed amount must be written in words and ﬁ gures. It is recommended that the prescription should state the 
name of the pharmacy where the prescription is to be dispensed, how often the prescription should be dispensed and whether the dose should be consumed under supervision. Installment prescrip-tions for daily dispensing are available in the UK for burpenor-phine and methadone. Only doctors in possession of a Home Ofﬁ  ce 
license are able to prescribe heroin for the treatment of opioid dependence.
(34)

(34)
Opioid overdose management
Opioid overdose management training is particularly important as early recognition (Table 4.2.3.1.6) of an opioid overdose and prompt action (Table 4.2.3.1.7) can save lives. The antidote to her-oin is naloxone and this should be given if an opioid overdose is suspected. Although intravenous naloxone is quicker acting, venous access may be difﬁ  cult and therefore, intramuscular injection may 
be preferable and also results in a more gradual reversal of theoverdose which may be less likely to provoke aggression. Hospital monitoring should always be recommended, since the plasmahalf-life of naloxone is shorter ( <1 h) than the physiological effects

of heroin (4–6 h) and methadone (24–36 h). In addition many overdoses are a result of concomitant substance use—the effects of which will not be reversed by naloxone alone. Opioid overdoses involving buprenorphine (partial agonist) will not be readily be reversed by naloxone; however buprenorphine is believed to have 
much less respiratory depressant effects.
The supply of ‘take home’ emergency naloxone may help reduce 
opioid related overdose deaths. It has, therefore, been advocated that providing take-home naloxone in combination with opioid overdose management training to opioid using patients and their families may help reduce deaths.
(35)
Table 4.2.3.1.6  Recognition of an opioid overdose
Recognition
Respiratory Arrest with a pulse
Pinpoint pupils (unreactive to light)Snoring giving way to shallow respiration
Respiratory Depression ( <8 breaths per min)
Bradycardia and hypotensionVarying degrees of unconsiousness4.2.3.1 opioids: heroin, methadone, and buprenorphine

SECTION 4  clinical syndromes of adult psychiatry 480
Y oung people with opioid problems often have other emotional 
and/or behavioural problems, and frequently fall between the adult and child psychiatric services as well as addiction services, compounding the difﬁ  culties in providing effective services to this 
group. Increasingly dedicated services have recently been devel-oped and these integrated services focus as much on the family and re-integration with education as they do on substance use issues. Approaches effective for the adult population may be less effective in a group with less developed emotional and cognitive abilities. Separation of such a service from adult providers would also assist in preventing experienced drug users from inﬂ  uencing more naive 
users. Ultimately, a tiered approach would appear appropriate, since it would allow maximum utility of current services and focused

users. Ultimately, a tiered approach would appear appropriate, since it would allow maximum utility of current services and focused 
development of new services. Generic services in primary health 
care could provide accurate screening with initial referral to youth-oriented services within existing departments. Beyond this, referral to specialist and super-specialist regional services could be employed to provide secure environments with the option of resi-dential rehabilitation and therapeutic communities. Once engaged they may beneﬁ  t from a range of possible therapies from family 
work and cognitive behavioural therapy to pharmacotherapy and self-help groups.
Pregnancy and breastfeeding
Maternal opioid use poses a risk to both the mother and foetus. Pregnancy can be a speciﬁ  c point when women try to address their

Maternal opioid use poses a risk to both the mother and foetus. Pregnancy can be a speciﬁ  c point when women try to address their 
opioid use problem. The management of the pregnant opioid user should follow the same guiding principles as for other opioid users; additionally, there should be close liaison between addictions and maternity services, the general practitioner and other relevant agencies (Table 4.2.3.1.8).
Women who are already on methadone maintenance treatment 
can remain on methadone but should be encouraged to stop illicit opioid use. For women who are not prescribed methadone, the ﬁ  rst

can remain on methadone but should be encouraged to stop illicit opioid use. For women who are not prescribed methadone, the ﬁ  rst 
step is to initiate stabilization on methadone. Methadone mainte-nance may continue at a stable dose throughout pregnancy. During the third trimester, maternal metabolism may increase the need for methadone and so the dose may need to be increased or alterna-tively the daily dose could be split. Methadone increases the risk of respiratory depression in the neonate and should always be 
pre-considered for the delivery plan. Women prescribed opioids 
may also need increased pain relief during delivery. The long-term outcome in women who enter methadone treatment programmes during pregnancy is better in terms of their pregnancy, childbirth, and infant development, irrespective of continuing illicit drug use.
(36) Methadone is not contraindicated for breast feeding.

Some women prefer to be abstinent from opioids during 
pregnancy. These women will often need a gradual pharmacologically assisted detoxiﬁ  cation, which should be avoided in the ﬁ  rst trimester, 
ideally undertaken in the second trimester and undertaken with caution in the third trimester. Detoxiﬁ  cation is best under-
taken within a dedicated inpatient facility, however, this may not always be possible and therefore community detoxiﬁ  cation 
can be undertaken. During stabilization on methadone or detoxiﬁ  -
cation, it is important to prevent the pregnant woman experienc-ing opioid withdrawal as this is dangerous for both mother and fetus.
Currently, there is insufﬁ  cient evidence regarding the use of 
buprenorphine during pregnancy or breastfeeding to be able to deﬁ ne its safety proﬁ  le. However, women well maintained on 
buprenorphine prior to pregnancy refusing alternative pharmaco-

therapy could be kept on buprenorphine following full informed consent.
Forensic
It has been estimated that up to two-thirds of people arrested have taken substances prior to arrest, whilst approximately 15–50 per cent of the prison population were previously dependent on drugs or alcohol. It is difﬁ  cult to estimate exact opioid use and depen-
dence, but approximately one-ﬁ  fth of the prison population injects 
drugs. Access to illicit substances is not prevented by imprison-ment; indeed some users may increase or start using drugs whilst imprisoned.
(37) Improving identiﬁ  cation of drug users before sen-
tencing is important. In addition, identiﬁ  cation of drug related

tencing is important. In addition, identiﬁ  cation of drug related 
crimes and offering court diversion schemes with drug treatment interventions can be an alternative to a custodial sentence. Prisoners will beneﬁ  t from education, good primary health care, blood borne 
virus testing, and hepatitis vaccination. In addition, prisoners can undertake opioid detoxiﬁ  cation or commence/continue opioid 
maintenance treatment whilst in prison. Release from prison is associated with extremely high risk of opioid overdose death, particularly in the ﬁ  rst few weeks, and therefore quick access to 
drug services following release (or prior to release) may reduce deaths.Table 4.2.3.1.7  Management of an opioid overdose
Check area safe, then try to rouse overdose victim
If unrousable - Call for help/ambulanceCheck airway and breathing
a. If not breathing, give 2 rescue breaths
b. If breathing — place in recovery position

Administer 0.4 mg Naloxone Intramuscularly — Increase dose until adequate 
reversal achieved
Consider use of high ﬂ  ow oxygenPatient to have medical monitoring after naloxone, as opioid overdose may 
re-emerge.
Patients may need additional doses of naloxoneTable 4.2.3.1.8  Aims of managing the pregnant drug user
X Engage and maintain contact with the patient and partner.
X Aim to reduce risk-taking behaviours (sharing needles, prostitution).
X  Stabilize on oral methadone maintenance treatment (or extremely slow 
detoxiﬁ  cation, if required).
X Ensure that other drug and alcohol use are assessed routinely.
X  Provide health and psychosocial care including blood borne virus screening.
X  Close liaison with multi-agency teams including possible social work 
assessment.
X Social stability and provisions for motherhood.

481
Accessing treatment and the range 
of services
Those who experience problems with opioids may present to a 
wide range of professionals within the health-care, social, and legal systems. The range of treatment options available from statutory and non-statutory agencies in any particular area will vary, as will the provision of either maintenance or detoxiﬁ  cation for opioid 
dependents depending upon differing treatment philosophies and treatment settings.
Outcomes
Heroin dependence is a chronic relapsing condition and opioid use reduces morbidity and mortality more than any other drug use.
(38)
Treatment saves lives and improves psychosocial function as well as reducing risk to both the individual and the community. Outcomes are broadly comparable to those seen with other chronic medical conditions.
(39) Abstinence rates following treatment vary widely, 
but 10 to 40 per cent of treated patients are still drug free at 6 months.

(40) The majority of those who relapse following treat-
ment do so within 3 months of discharge. Longer treatment is asso-ciated with better outcomes and greater pre-treatment severity of psychopathology is associated with worse outcomes. Long-term follow-up studies suggest that successful and lasting cessation of opioid use can be a very slow process and becomes increasingly unlikely if users continue into their late thirties.
Results from three longitudinal studies ranging from 3–5 years 
based in the United Kingdom, Australia and United States of America have shown that treatment leads to better outcomes against all parameters as compared to no treatment.
(41,42,43)
Patients who enter drug treatment are more likely to signiﬁ  cantly

Patients who enter drug treatment are more likely to signiﬁ  cantly 
reduce use of heroin and other illicit drugs and longer treatment times have been associated with better treatment outcomes. Reductions in heroin use have also been mirrored by reductions in heroin overdose rates. Therefore opioid treatment increases morbidity and mortality in opioid users.
The Australian Treatment Outcome Study (ATOS) reported that 
half the number of opioid overdoses occurred in the participants in treatment at 1 year as compared to the same participants prior to entering treatment. In addition this study showed that levels of psychopathology reduced, physical health improved and crime rates in this population reduced following treatment.
(43) The National 
Treatment Outcome Research Study (NTORS) based in the UK had increased rates of abstinence, reduced heroin use and reduced injecting and sharing of injecting related equipment with both res-idential and community treatment.

(42) Findings from the Drug 
Abuse Treatment Outcome Studies (DATOS) based in the USA were similar to both the UK and Australia studies.
(41)
Longer term outcomes have been observed in a study following 
up 581 male heroin users since 1962. At the 33-year follow up, 284 subjects were dead and 242 were interviewed. Over a ﬁ  fth were 
still using heroin and 40.5 per cent admitted to using heroin inthe last year. There were high rates of health problems, mental health problems, and criminal justice system involvement. Heroin abstinence was associated with improved outcomes in all these domains. Deaths increased steadily over time with a relatively stable pattern of heroin use in the subjects.
(44) A further analysis of
the results assessed years of life lost through heroin use andconcluded that on average, 18.3 years of potential life were lost 
before the age 65, which is signiﬁ  cantly higher than that of US
population.(45)

Opioid dependence is a chronic relapsing and remitting disorder affecting a large proportion of people throughout the world with severe physical, psychological, and social consequences. Opioid overdose and spread of blood borne viruses are major causes of morbidity and mortality. Assessment of opioid use and dependence should be systematic and conﬁ  rmation of dependence is of para-
mount importance before initiating treatment. The prescription of substitute opioids should be managed carefully to prevent harm, diversion to others and improve safety. Management of opioid dependence can greatly improve outcomes and may be based on opioid maintenance stabilization or detoxiﬁ  cation combined with 
psychosocial interventions.
Department of Health (England) and the developed administrations. Drug

Department of Health (England) and the developed administrations. Drug 
misuse and dependence: UK guidelines on clinical management. 1999. HMSO, London. http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_4078198.pdf
National Treatment Agency for Substance Misuse website for guidelines. 
http://www.nta.nhs.uk/
The Cochrane Library for Cochrane Systematic Reviews on Opioids. http://
www3.interscience.wiley.com/cgi-bin/mrwhome/106568753/HOME
National Institute for Clinical Excellence. www.nice.org.uk/
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4.2.3.2 Disorders relating to the use 
of amphetamine and cocaine
Amphetamine and cocaine are classed as stimulant drugs, although

Amphetamine and cocaine are classed as stimulant drugs, although 
the distinction between stimulants and depressants can be criticized on the grounds that the same drug may have both actions in turn. This does indeed occur with amphetamine and cocaine, but the initial desired effects are increased energy and activity, and elevation in mood. These appear to be mainly due to enhanced central trans-mission of dopamine and noradrenaline (norepinephrine), with a similar enhancement of serotonin playing a less certain role.
Pharmaceutical preparations of amphetamine were previously 
widely used for treatment of depression and obesity, with some misuse of these occurring. In the period since the 1970s ofincreasing recreational drug use, the powder preparation of ‘street’

483
amphetamine (commonly known as ‘speed’ or ‘whizz’) has largely 
displaced the pharmaceutical forms to become a common drug of misuse in many countries. The powder is typically very impure and constitutes a racemic mixture of d- and l-isomers, with the l-form being relatively inactive. A stronger street preparation is the ‘base’ , sometimes more a moist paste, and both these forms of the drug may be swallowed (either on their own or in a drink), snorted, or injected. (For the methylated forms ‘ecstasy’ and ‘crystal meth’ , see Chapter 4.2.3.5.)
The coca shrub is indigenous to countries in South America,

The coca shrub is indigenous to countries in South America, 
where the leaf is chewed, and use of the derived cocaine powder has spread extensively to the United States and elsewhere. The powder may be injected, sometimes along with heroin, by polydrug users, or snorted, the image of which is sometimes linked with executive lifestyles. Cocaine has become more dangerous as usage has gradu-ally transferred in many countries to the ‘crack’ form, which is made from cocaine hydrochloride powder in a simple chemical process, and is more potent in its effects and withdrawal effects. Very rapid increases in blood levels of the drug can be achieved by smoking crack, and this is the usual route, although it is injected by committed intravenous drug users.

The effects and withdrawal effects of amphetamine and cocaine can be considered together, as the main features are equivalent. However, amphetamine has a slower onset of action than cocaine and longer elimination half-life, while crack is the most quickly absorbed of the cocaine preparations. This is reﬂ  ected not only in 
the generally more intense effects of cocaine than amphetamine, but in the timescales involved. Thus an amphetamine user may experience desired effects, unwanted mental effects, and withdrawal features over the course of a few days, while a crack user can report the same sequence occurring in a matter of hours or even less. The main effects and withdrawal effects of these two stimulant drugs are shown in Table 4.2.3.2.1. 
The list of effects can be seen as merging from the desired to the

The list of effects can be seen as merging from the desired to the 
undesired. These drugs are typically taken in situations where stim-ulation is the aim, with sleep and eating regarded as hindrances. Mood is elevated, but characteristically this progresses to suspicion, in which true paranoid symptoms may be experienced. This is usually recognized by the individual as indicating that the episode of use should be terminated, but if use persists symptoms may become severe, or a more confused state develop. After stopping the drugs there are typically withdrawal effects of depressed mood, hyperphagia, and hypersomnia; no consensus exists as to whether such features are best viewed as ‘rebound’ symptoms, a truer 
withdrawal syndrome, or simply users catching up on sleeping and eating after a period without either.
Such withdrawal features have been delineated most closely 
in relation to cocaine. A three-stage process has long been recognized

(1): initially agitation, anorexia, and acute craving; 
second, excessive tiredness, depression, and hyperphagia; ﬁ  nally, a 
normalization of most features, but a return of craving when triggered by environmental cues. This description is from before the escalation in crack use, and depression, craving, and agitation especially are often much more severe with this form of the drug. While environmental cues are clearly relevant in precipitating the use of any drug, a powerful surge of craving on encountering situations associated with previous use appears particularly charac-teristic of cocaine and crack.
(2) The three-stage description of with-
drawal features suggests that this phenomenon may occur after months or even years of abstinence.
Are amphetamine and cocaine addictive?

It is commonly observed that amphetamine and cocaine are non-addictive, or cause psychological but not physical dependence. Such observations rest on a distinction in which the condition of addiction, or physical dependence, requires visible bodily with-drawal symptoms, but critics claim this is of limited meaning now that there is an understanding of the neurobiological basis of drug withdrawal states. The current classiﬁ  cation systems do retain some 
distinctions between physical and psychological dependence, and the issue is largely one of deﬁ  nition and semantics. The credibility 
of the label ‘non-addictive’ is certainly tested by individuals who have injected amphetamine 10 or more times every day for many years, or who spend vast amounts of money using crack in a highly compulsive manner.

Table 4.2.3.2.2 shows the classiﬁ  cation within ICD-10 and DSM-
IV-TR of disorders that may relate to the use of cocaine. In both systems the same diagnoses can be applied to amphetamine, in ICD-10 within a category ‘other stimulants’ .
Importantly, the list of diagnoses in ICD-10 is a standard one to 
be used across all psychoactive substances, with the second digit of the code number simply changed according to substance, and so does not imply that all those conditions can be caused by amphet-amine or cocaine. The DSM-IV-TR listing is somewhat more speciﬁ  c, 
in that the diagnoses are selected from a wider general list of con-ditions which can apply to the range of substances. In this way the DSM-IV-TR classiﬁ  cation recognizes that cocaine and amphet-
amine can produce states of dependence and withdrawal, as well as psychosis, affective disorders, and the other conditions included.
Diagnosis

Diagnosis
The use of amphetamine or cocaine can be detected by drugscreening of a plain urine sample, in laboratory testing or with instant kits. The importance of urine testing as a relatively simple procedure to employ, in any setting, in cases where drug use is sus-pected must be emphasized, as it is surprisingly often neglected. The two main limitations are possible doubts about authenticity, where mouth swabs for oral mucosal transudate can be a useful Table 4.2.3.2.1  Effects and withdrawal effects of amphetamine and 
cocaine
Effects Withdrawal effects
Increased energy Depression
Hyperactivity IrritabilityEuphoria AgitationReduced appetite Craving
Insomnia Hyperphagia
Paranoid symptoms HypersomniaConfusion4.2.3.2 disorders relating to the use of amphetamine and cocaine

SECTION 4  clinical syndromes of adult psychiatry 484
alternative, and the short time for which drugs remain detectable 
in urine—as little as 24 h for cocaine. By contrast drugs remain in hair from the head or other parts of the body for the whole period of growth, but this technique which gives much longer-term infor-mation is a specialized one.
Obtaining a history and compliance with sampling may be 
particularly problematic in psychotic states. In such conditions it is also important to recognize that detected drug use may be incidentalrather than necessarily causative.
In most countries, the use of illicit drugs is commonest among young males of lower socio-economic status. Stimulant use overall reﬂ ects this, although of the various drugs of misuse, cocaine 
powder has been exceptional in the extent of usage also by more afﬂ uent individuals.
The biggest epidemic of cocaine use outside South America has 
been in the United States, where it peaked in the mid-1980s.

(3)
Household surveys at that time estimated that approximately one-tenth of the population had used the drug; the same epidemio-logical method has charted the subsequent general decline inoccasional use, but an increase in more dependent use of crack. Cocaine use in other countries has not generally spread as widely as was predicted from the United States experience. In Europe the pop-ulation lifetime prevalence of cocaine use has remained in low single-ﬁ gure percentages,
(4) much of it among inner-city polydrug users, 
although snorting cocaine powder is seemingly increasing among 
young people, rather displacing the recreational use of ‘ecstasy’ .Even in areas where stimulant use is common, such users tend

young people, rather displacing the recreational use of ‘ecstasy’ .Even in areas where stimulant use is common, such users tend 
to present relatively rarely to treatment services. Priority is gener-ally given to opioid substitution treatment of heroin addicts, and so service statistics will nearly always underestimate stimulant problems.
Aetiology
Broadly the same familial, social, and psychological factors are relevant in the aetiology of amphetamine and cocaine misuse as in other forms of drug misuse. Approximately half of the drug misus-ers are deemed in studies to have an underlying personality disorder,
(5)
usually of the antisocial type, although the ﬁ  gure has sometimes 
been found to be lower for stimulant misusers than for those dependent on opiates. This may be partly methodological, to do with the difﬁ  culty in distinguishing true personality characteristics

been found to be lower for stimulant misusers than for those dependent on opiates. This may be partly methodological, to do with the difﬁ  culty in distinguishing true personality characteristics 
from behaviours inherent in the activity of highly dependent drug misuse, but is probably also a reﬂ  ection of the use of stimulant 
drugs by a generally broader population.
Course
A far greater proportion of amphetamine and cocaine misuse than opiate misuse is recreational in nature, with few signiﬁ  cant compli-
cations if the medical harms are avoided. It is assumed that the vast majority of those who are identiﬁ  ed in school and teenage surveys as

cations if the medical harms are avoided. It is assumed that the vast majority of those who are identiﬁ  ed in school and teenage surveys as 
having used stimulants simply give them up in due course, although little systematic data is available. Complications and involvement with treatment services are more likely where there is dependent usage, and there may be psychiatric contact in episodes of psychosis. A very small proportion of amphetamine injectors progress to high-dose daily usage, while the heavy use of cocaine appears to be less sustainable and is therefore usually periodic in nature.
Other drug use

After being stimulated with amphetamine or cocaine, many individuals will use sedatives such as alcohol, benzodiazepines, or cannabis to ‘come down’ from their drug. Increasingly heroin is being used for this purpose, sometimes to the point of becoming dependent on the opiate and requiring substitution treatment.The use of cocaine in particular is commonly encountered as asecondary form of drug misuse in methadone patients,
(6) with 
some individuals undoubtedly switching their preferred illicit drug from heroin to cocaine when treatment is established.
Prognosis
The drug misuse literature in general would suggest that stimulant use is more likely to progress and become problematic in individu-als with associated personal or social difﬁ  culties or psychiatric
disorder. Usage by individuals with severe mental illness, which 
often contains an element of ‘self-medication’ of distress even

often contains an element of ‘self-medication’ of distress even 
though in the long run stimulants will render symptoms worse, can be particularly entrenched.
(7)
Complications
Many of the complications of amphetamine and cocaine misuse are complications of drug misuse in general, including those related to injecting. The range includes general physical decline, Table 4.2.3.2.2  Classiﬁ  cation of disorders relating to cocaine in 
ICD-10 and DSM-IV-TR
F14.0 Acute intoxication 292.89 Cocaine intoxication
292.81 Cocaine intoxication delirium
F14.1 Harmful use 305.60 Cocaine abuseF14.2 Dependence 
 syndrome304.20 Cocaine dependence
F14.3 Withdrawal state 292.0 Cocaine withdrawal
F14.4 Withdrawal state 
 with delirium
F14.5 Psychotic disorder 292.11 Cocaine-induced psychotic 
 disorder, with delusions
292.12 Cocaine-induced psychotic 
 disorder, with hallucinations

292.84 Cocaine-induced mood disorder292.89 Cocaine-induced anxiety disorder292.89 Cocaine-induced sexual 
 dysfunction
292.89 Cocaine-induced sleep disorder
F14.6 Amnesic syndromeF14.7 Residual and late-
 onset psychotic  disorder

485
weight loss, dental problems, infective complications ranging 
from abscesses to hepatitis and infection with the human immuno-deﬁ ciency virus (HIV), reduced foetal growth in pregnancy, mood 
disturbances, and various social problems. Complications in thefollowing areas are somewhat more speciﬁ  c to stimulant misuse:
X Cardiovascular—hypertension, arrhythmias, myocardial 
infarction, cerebrovascular accident
X Obstetric—premature labour, placental abruption
X Psychiatric—anxiety, depression, aggressive behaviours, psychosis
X Other—perforation of nasal septum (cocaine snorting)
The cardiovascular problems relate to increased catecholamine 
secretion, and represent the most serious hazard of cocaine abuse.(8)
With obstetric complications, it is difﬁ  cult to separate the effects of 
drugs from other risk factors such as poor diet, smoking, or adverse social conditions, but there appears to be a particular link between stimulants and placental abruption.

There are also various psychiatric disorders that are particularly 
associated with amphetamine and cocaine misuse. Anxiety as a symptom is common in relation to the agitation produced by the drugs, while depression is a classic withdrawal effect. An assessment of the true clinical signiﬁ  cance of these features therefore requires 
withdrawal from drugs, while in acute presentations both can be extremely distressing. Aggressive behaviour may be due to an underlying personality disorder, but it is also characteristic of with-drawal from crack cocaine when severe craving is experienced. Paranoid psychosis, sometimes indistinguishable from an acute 
schizophrenic episode, is the best-known complication of stimu-lant misuse. The earliest descriptions were of cases where symp-

toms quickly subsided after withdrawal of the drugs, but it is now recognized that through mechanisms which represent a kind of sensitization, symptoms which are drug-induced can persist and recur even with avoidance of substance use.
(9)
Treatment
Evidence
A very large number of medications have been investigated in cocaine misuse, mainly compounds which through actions on cat-echolamines or serotonin could be expected to alleviate withdrawal effects. After decades of such work the evidence is very discourag-ing, with no medications consistently found to reduce stimulant abuse.
(10) Inpatient programmes and psychological treatments 
basically represent modiﬁ  cations of those approaches used across

basically represent modiﬁ  cations of those approaches used across 
all forms of drug misuse, although cocaine abuse appears particu-larly amenable to the ‘contingency management’ approach of providing material incentives for abstinence.
(11)
Faced with the limitations in treatment for these forms of drug misuse that have high morbidity and mortality, drug services have had to consider how best to achieve some beneﬁ  ts in terms of very 
practical management.
(12) The factors that appear important in 
such provision are:
X speciﬁ  c outreach programmes
X harm-reduction approaches
X rapid response where necessaryX targeted use of treatments
X admission in severe cases
T o engage stimulant users at all can require outreach aimed at

T o engage stimulant users at all can require outreach aimed at 
the subcultural groups in whom usage is common. Basic harm-reduction measures must be offered, including drug information, education about health risks, advice to reduce damaging injecting practices, and the provision of clean equipment. Counselling of a 
supportive or more behavioural kind may be provided by various 
types of agency.
The periodic nature of stimulant problems means that rapid 
response can be important, for instance in states of acute crack withdrawal or psychiatric disturbance. Use of tranquillizers and antipsychotic medications may be necessary for some presenta-tions, while ﬂ  uoxetine appears to be increasingly favoured over

other antidepressants, due to a possible anticraving effect and good acceptability. Inpatient admission can be required in cases where no long-term measure is able to make much impact between acute crises. The possibility of any substitute prescribing in stimulant misuse is highly controversial, with some services seeing a role for oral dexamphetamine in heavily dependent amphetamine users experiencing extreme problems from injecting.
(13)
Drug-induced psychosis
The two aspects of management of this complication are the treat-ment of psychotic symptoms and the withdrawal of the drug which is thought to be causative. The latter can be very problematic other than as an inpatient, and is not guaranteed even then. In practice, ongoing low-grade psychotic states in individuals who have not completely stopped drug use are common, and treatment may have to be attempted in such circumstances. The use of antipsychotic medications does not differ signiﬁ  cantly from that in psychoses not

produced by drugs.
The prevention of drug misuse lies largely outside the clinical domain, in the areas of education, enforcement and social improve-ment. A more biological development in cocaine misuse of vaccination, whereby limited exposure produces antibodies to subsequently block the drug’s effects, remains experimental.
National Institute of Drug Addiction-Research Report for Cocaine 
Addiction: www.nida.nih.gov/ResearchReports/cocaine.html
Amphetamine Dependence: www.mentalhealth.com/dis/p20-sb02.html
Sadock, B.J. and Sadock, V .A. (2003). Kaplan and Sadock’s synopsis of 
psychiatry; Substance-related disorders, Chap. 12. Lippincott,Williams & Wilkins, Philadelphia.
European Monitoring Centre for Drugs and Drug Addiction. (2006). 
Annual report: the state of the drugs problem in Europe . Ofﬁ  ce for 
Ofﬁ cial Publications of the European Communities, Luxembourg.

Chapter 4, Amphetamines, ecstasy and other psychotropic drugs, and Chapter 5, Cocaine and crack cocaine.
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SECTION 4  clinical syndromes of adult psychiatry 486
 2. van de Laar, M.C., Licht, R., Franken, I.H.A., et al. (2004). Event-related 
potentials indicate motivational relevance of cocaine use in abstinent 
cocaine addicts. Psychopharmacology ,177, 121–9.
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abuse and dependence. Journal of Clinical Psychopharmacology ,15,
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Cocaine and crack cocaine. In Annual report: the state of the drugs 
problem in Europe . Ofﬁ  ce for Ofﬁ  cial Publications of the European 
Communities, Luxembourg.
 5. Grant, B.F., Stinson, F.S., Dawson, D.A., et al. (2004). Co-occurrence of 
12-month alcohol and drug use disorders and personality disorders in 
the United States. Archives of General Psychiatry ,61, 361–8.
 6. Williamson, A., Darke, S., Ross, J., et al. (2006). The association

 6. Williamson, A., Darke, S., Ross, J., et al. (2006). The association 
between cocaine use and short-term outcomes for the treatment of heroin dependence: ﬁ  ndings from the Australian treatment outcome 
study. Drug and Alcohol Review ,25, 141–8.
 7. Seivewright, N., Iqbal, M.Z., and Bourne, H. (2004). Treating patients 
with comorbidities. In Drug treatment: what works?  (eds. P . Bean and 
T. Nemitz), pp. 123–41. Routledge, London.
 8. Edgred, M. and Davis, G.K. (2005). Cocaine and the heart. Postgraduate 
Medical Journal ,81, 568–71.
 9. Curran, C., Byrappa, N., and McBride, A. (2004). Stimulant psychosis: 
systematic review. The British Journal of Psychiatry ,185, 196–204.
10. de Lima, M.S., de Oliveira Soares, B.G., Alves, A., et al. (2002). 
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11. Higgins, S.T., Heil, S.H., Dantona, R., et al. (2007). Effects of varying

11. Higgins, S.T., Heil, S.H., Dantona, R., et al. (2007). Effects of varying 
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12. Seivewright, N., McMahon, C., and Egleston, P . (2005). Stimulant use 
still going strong. Advances in Psychiatric Treatment ,2, 262–9.
13. Grabowski, J., Shearer, J., Merrill, J., et al. (2004). Agonist-like 
replacement pharmacotherapy for stimulant abuse dependence. Addictive Behaviors ,29, 1439–64.
4.2.3.3 Disorders relating to use 
of PCP and hallucinogens
PCP
Phencyclidine (PCP , ‘angel dust’) is an arylcyclohexylamine dissocia-
tive anaesthetic. It was ﬁ  rst abused in the United States in New Y ork 
and San Francisco in the 1960s, but abuse declined when a broad 
range of adverse complications was noted.(1)

While use of the unadulterated drug occurs, PCP is more frequently mixed with LSD or cannabis. The drug may be ingested or injected, 
but is more commonly smoked or snorted. Data suggest use in the United States and Europe. In the United States, a stable trend of 3 per cent of high school seniors have tried PCP at least once.
(2)
It trafﬁ  cs under a long and colourful list of street names. It has been 
suggested that any illicit smoked drug with an unrecognized street name (dust, mist, THC, embalming ﬂ  uid, inter alia ) should be 
considered PCP until proven otherwise.Acute physiological effects

The drug has a delayed onset of activity when taken orally. Unlike the major hallucinogens, PCP requires doses in milligrams to be effective, a factor facilitating toxicological identiﬁ  cation. When 
smoked, the onset of its main effects occurs immediately. The drug has particular afﬁ  nity for the sigma opioid receptor, and non-com-
petitively blocks the N-methyl- d-aspartate-type excitatory amino 
acid receptor. Other effects appear to be mediated indirectly by catecholamine release, cholinergic stimulation, and serotonergic receptors.
DSM-IV lists as criteria for acute  PCP intoxication the following:
X agitation
X belligerence
X impaired judgement
X nystagmus
X hyperacusis
X hypertension
X tachycardia
X numbness
X ataxia
X dysarthria
X rigidity
X salivation
X seizures
X coma

X numbness
X ataxia
X rigidity
X seizures
X coma
It is clear from this daunting inventory that impaired judgement 
is likely to be present beforehand in any person intentionally choos-ing to abuse this drug.
Adverse effects
PCP affects not only adults, but fetuses and nursing infants.(3)
Neurological consequences in infants include poor attention, hypertonia, and depressed neonatal reﬂ  exes.
(4)In vitro  studies show 
that PCP causes inhibited axon outgrowth, degeneration, and death in human fetal cerebral cortical neurones.
(5)
In adults signs of severe PCP toxicity include:
X hyperthermia
X opisthotonus
X cardiac arrhythmia
X stroke
PCP is capable of provoking extreme muscular agitation, rhab-
domyolysis and renal failure in 2.5 per cent of users.(6) DSM-IV

X stroke
domyolysis and renal failure in 2.5 per cent of users.(6) DSM-IV 
lists psychiatric effects of PCP including intoxication, delirium, PCP-induced psychotic, mood, and anxiety disorders, and PCP abuse and dependence. A criterion for diagnosis is the emergence of the disorder within a month of drug use.
PCP delirium
Unlike acute intoxication with other hallucinogens, PCP delirium is associated with neurological disturbances. A continuum of effects is noted depending on dose.
(7) Psychiatric symptoms occur early in

487
drug use, with stupor and coma occurring later. Shortly after drug 
use, patients appear confused and ataxic. Analgesia in ﬁ  ngers and 
toes may be described. PCP can produce complex hallucinations resembling LSD intoxication. Differentiating the two drugs in emergencies is important, since high-potency neuroleptics, which are useful in PCP toxicity, may exacerbate LSD, while the use of benzodiazepines, helpful in acute LSD toxicity, may disinhibit an assaultive PCP patient. Unlike LSD, PCP is readily identiﬁ  ed in

routine toxicological screening of blood and urine, but such data may not be readily available. One rapid bedside technique to differentiate the two drugs is the palm sign. The examiner asks the patient to describe the names of all the colours seen in the examiner’s outstretch palm. A typical LSD patient reports a vision of multiple colours and images. A PCP patient simply attacks the hand. Dexterity of the examiner is suggested. Unfocused aggression makes PCP delirium a particularly dangerous disorder. The spectrum of violence includes both suicide and homicide.
(8) The technique 
of ‘talking down’ acutely toxic patients is contraindicated. Environmental stimuli should be minimized, and the patient provided with protective supervision. The use of physical restraints is relatively contraindicated because of the potential for rhabdomyolysis.
Speciﬁ  c treatments involve:
X intravenous naloxone to rule out narcotics overdose
X activated charcoal

X acidiﬁ  cation of the patient’s urine with vitamin C, ammonium 
chloride, cranberry juice
X diuresis with frusemide (furosemide, Lasix)
X antihypertensives
X high-potency neuroleptics or barbiturates
PCP has mixed agonist and antagonist effects at cholinergic 
receptors. Anticholinergic drugs may precipitate a synergistic reaction with PCP , worsening delirium. Thus, low-potency neuro-leptics, tricyclic antidepressants, and the anticholinergic antipar-kinsonian drugs should be avoided.
PCP-induced psychotic disorder
PCP delirium may evolve into a chronic PCP psychosis that isdifferentiated from schizophrenia only with difﬁ  culty. Alternatively,

PCP delirium may evolve into a chronic PCP psychosis that isdifferentiated from schizophrenia only with difﬁ  culty. Alternatively, 
a PCP delirium may clear, only to be replaced by the insidiousonset of a post-PCP psychotic disorder. Certain features ofPCP psychosis, namely neurological abnormalities, dose-relatedseverity of symptoms, and regularity of the length of illness,are not noted with other psychedelic drugs, leading to thesuggestion that PCP psychosis is a toxic drug effect rather than a functional illness. Four classes of agents are reported to help PCP psychosis:
X benzodiazepines
X neuroleptics
X acetylcholinesterase inhibitors (physostigmine)
X catecholamine depleters (reserpine)
Otherwise, treatment considerations are those for PCP delirium. 
The long-term prognosis for this disorder appears to be poor, according to data from an 8-year follow-up of 10 patients.
(9)PCP abuse, dependence, and organic mental disorder

Rhesus monkeys will self-administer PCP in a dose-dependent way,
(10) suggesting that repeated abuse in humans may be associ-
ated with psychophysiological dependence. This in turn is likely to be associated with a decline in social and occupational function characteristic of other forms of addiction. Because of its wide-spread neuropsychological effects, any intentional, informed use of PCP should be considered maladaptive. For the habituated patient, long-term treatment is indicated. Issues that should be addressed in the process are:
X emotional lability
X cognitive defects
X depression
X possible PCP withdrawal
X nutritional status
Many of the treatments applicable to patients addicted to the

Many of the treatments applicable to patients addicted to the 
opiates, alcohol, and cocaine apply to this population. Several aspects of treating the PCP patient depart from the more conven-tional addiction treatments. A triad of confusion, decreased cogni-tive function, and assaultiveness mark an organic mental disorder associated with PCP use. Reduced cognition is a barrier to recovery that must be recognized and addressed in any prospective treat-ment plan. Neuropsychological assessment is helpful in this regard. Secondly, there is murine evidence that PCP is sequestered in fat and by melanin for at least 3 weeks following a single exposure.
(11)
Conditions associated with weight loss are likely to release long-held PCP into the blood and brain.
Hallucinogens

(11)
Agents that alter perception and mood without disorientation typify hallucinogenic drugs. They have been known and used for mil-lennia for purposes ranging from magical to medical. Anthropologists trace back the earliest use of hallucinogens to Paleolithic Europe, although 80 per cent of extant hallucinogenic plants are to be found in the New World. Galen ( ad 130–200) wrote that it was customary to 
give dinner guests hemp seeds to promote the evening’s proceedings. The ergot-bearing fungus Claviceps purpurea  infected rye in tenth-
century France and claimed 40 000 lives. Despite such calamities, ergot continued to be used by midwives in medieval Europe. In search of a benign ergot derivative for use in childbirth, Albert Hofmann synthe-sized lysergic acid diethylamide (LSD-25) in 1938, described in his 
classic monograph, LSD: my problem child .

In 1947, Stoll in Switzerland published the ﬁ  rst experimental use 
of LSD in psychiatry. Intelligence agencies worldwide seized on the 
misnomer of LSD as an instrument of ‘mind control’ . Academicians including Sandison and Elkes in England, Cohen and Eisner in the United States, Leuner in Germany, and Grof in Czechoslovakia engaged in human studies. But within a decade the drug the genie was out of the bottle, as the drug moved from the hands of scien-tists to clinicians, clergy, curious professors, and a widening num-ber of students on both sides of the Atlantic. Military investigators in the United States gave the drug surreptitiously to recruits. By the late 1960s LSD and cannabis led the way to a pandemic of drug abuse among the young.4.2.3.3 disorders relating to use of pcp and hallucinogens

SECTION 4  clinical syndromes of adult psychiatry 488
Drug preparations
Hallucinogenic drugs comprise not so much a single class of
compounds, but a multiple classes affecting different neuronalreceptors. Hofmann and Schultes describe 11 classes of hallucino-genic compounds which can be isolated from botanicals.
(12)
Hallucinogens are readily available. Botanicals are easily grown. Indole and phenethylamines can be easily synthesized, especially with the rise of the Internet. Chemically pure hallucinogens are psychoactive in microgram quantities, and are easily concealed, transported and sold, accounting for their enduring role asabusable substances.
LSD  is psychoactive in a single droplet of solvent. The drug is 
easily dissolved in an aqueous solution. Drops of the drug are placed on sugar cubes or blotting paper stamped with coloured cartoon ﬁ  gures to mark the drug’s location. Sheets of the paper are 
then distributed, and the ﬁ  gures ingested. Dosages commonly

then distributed, and the ﬁ  gures ingested. Dosages commonly 
range from 25 to 100 μg. A hallucinogenic trip can occur after 75 μg. Other hallucinogens, such as dimethyltryptamine, are injected. The serotonin-2A receptor has been shown to bind 
strongly to many hallucinogenic drugs, and these drugs appear to 
act as partial agonists.
(13)
Common botanical hallucinogens  include fungi and angio-
sperms (ﬂ  ower-bearing plants), of which approximately 100 are 
recognized with hallucinogenic properties. Ibogaine is derived from the root of the Tabernanthe iboga  plant cultivated in Gabon 
and eaten as a rite of passage. Ayahuasca is a tea of dimethyltrypt-amine from the Amazon vine, Banisteriopsis , potentiated by 
beta-carbolines which inhibit monoamine oxidase. Mescaline is a predominant hallucinogen in the cactus Lophophora williamsii .
Strips of cactus are cut from the plant, dried, and eaten. The Mexican mint, Salvia divinorum , contains a diterpene kappa-

opioid agonist. Salvia  is easily bought from the Internet from scores 
of Websites in the United States and Europe.
(14)
Hallucinogenic mushrooms  contain psilocybin and psilocin, 
which are phosphorylated hydroxylated congeners of dimethyl-tryptamine. Mushrooms are ingested for their effect, or brewed ﬁ rst and the broth consumed. Responses vary widely between
individuals and occasions. The American psychologist William James reported ingesting several dozen hallucinogenic mushrooms and only experiencing headache. Shulgin has synthesized andtested 179 phenylethylamines for hallucinogenic properties.Their effects on the human brain are complex and largely unknown.

Annual surveys in United States college students indicate that LSD use fell from 1995 to 2005 from a lifetime prevalence of 11.5 to 3.7 per cent. This was offset by an increase in the lifetime use of psilocybin mushrooms, from 6.5 to 10.6 per cent. This increase in the use of non-LSD hallucinogens is reﬂ  ected across secondary 
grades and young adults between 19 and 28 as well,
(1) and follows a 
period of rising LSD use in Germany, the United Kingdom, and the United States in the 1990s. Factors which may explain this decrease in LSD use include student reports of less availability, greater perceptions of risk, and the substitution of psilocybin and MDMA for LSD. A cross-sectional study of 904 women from 14 to 26 found that LSD users were more often Caucasian, victims of physical abuse, and suffering depression.
(15)Acute effects
The characteristic LSD trip comprises:
X autonomic arousal
X marked mydriasis
X sensory disturbances

Progressive modulations of visual imagery appear to be generated 
both from external objects and distortions of eidetic sources. Ordinarily benign objects may take on new emotional meanings. Geometric imagery may rise and fall before one’s eyes. A prevalent feeling one experiences is a sense of helplessness to control one’s streaming images and emotions, hence the hippie advice of ‘going with the ﬂ  ow’ . The loss of cognitive, perceptual, and affective 
control for some users leads to panic, which in turn results in the so-called ‘bad trip’ . As these effects decline, they may be replaced with a sense of oceanic well-being or residual paranoia.
Adverse reactions to hallucinogens include panic reactions associ-ated with a bad trip, hallucinogen persisting perception disorder, and prolonged psychoses.
(a) Panic reaction

Panic may arise during the acute drug experience. It is character-ized by a crescendo of rising anxiety accompanied by autonomic arousal in the context of streaming emotions and imagery. Mydriasis is greater than that seen in non-drug-induced panic. The use of an oral benzodiazepine such as diazepam 20 mg is utterly effective in stopping the panic within minutes.
(b) Hallucinogen persisting perception disorder (HPPD)
It became apparent within the ﬁ  rst few years of experimentation 
with LSD that this class of drugs was capable of inducing visual disturbances days to weeks following drug exposure. Subsequent research found that these disturbances, dubbed ‘ﬂ  ashbacks’ because

with LSD that this class of drugs was capable of inducing visual disturbances days to weeks following drug exposure. Subsequent research found that these disturbances, dubbed ‘ﬂ  ashbacks’ because 
of their evanescent visual appearance, appeared to be an intermit-tent form of post-drug visual disorder that in its extreme form was experienced continually. Thus, HPPD patients are capable of describing a range of visual disturbances that ﬂ  uctuate in intensity, 
but are observable from moment to moment (Abraham, 1983). Such imagery includes:
X geometric hallucinations
X false perceptions of movement
X afterimagery
X the perception of trails behind moving images
X pinpoint dots in the air (aeropsia)
Symptoms drawn by HPPD patients have been published on the 
Internet.(16) Patients also describe derealization and depersonaliza-
tion. Symptoms are intensiﬁ  ed by stimulation from:
X emergence into a dark environment
X marijuana
X amphetamines
X cocaine

489
X anxiety
X the stress of intercurrent illnesses
While recovery may occur over months and years following last drug 
use, approximately half of the patients so afﬂ  icted appear to develop a 
permanent alteration of the visual apparatus. Studies of psychophysics in HPPD patients reveal quantiﬁ  ed prolongations in afterimagery.
(17)
Neurophysiological studies conﬁ  rm cerebral disinhibition involving 
those regions of the cortex processing visual information.(18)
Management:  Because the disorder is exacerbated by psycho-
logical and physiological conditions of arousal, benzodiazepines have been helpful for management of visual symptoms.
(19) The 
results of these efforts are palliative at best, and complicated by the prospect of treating a drug abuser with an abusable substance. Recent case reports of treatment with sertraline, naltrexone, and clonidine are encouraging.
In addition to pharmacotherapy, HPPD patients often require

In addition to pharmacotherapy, HPPD patients often require 
supportive psychotherapy to deal with the issues of learning to cope with what may be a permanent alteration in perception. Therapy is also indicated to educate the patient, and prevent the development of common comorbid disorders in HPPD. These are:
X major depression
X panic disorder
X alcohol dependence from self-medication
(c) Psychosis
Evidence supporting the hypothesis that the use of potent hallucino-gens can trigger prolonged psychotic episodes is found in multiple longitudinal, cross-sectional, and case studies (Abraham et al. 1996).

Psychiatric patienthood appears to be a risk factor for the develop-ment of psychosis following LSD. The clinical picture of post-LSD psychosis resembles schizoaffective disorder more than it does schizo-phrenia, with the commonly added feature of chronic visual distur-bances. Clinically such patients resemble those with good-prognosis schizophrenia, since they possess more affect than those with poor prognosis, have less thought disorder, are more socially related, and appear to have fewer signs of negative schizophrenia. Mystical preoc-cupations reminiscent of acute drug experiences can predominate. Visual hallucinations often are of the variety that are seen in HPPD, although in contradistinction to such patients, psychotic patients 
may describe delusions and auditory hallucinations as well.
(20)
Management:  Atypical pharmacotherapies appear to have an

(20)
Management:  Atypical pharmacotherapies appear to have an 
important role in treatment, and in selected cases are preferable to dopamine-blocking neuroleptics. Reports in the literature describe cases responding to electroconvulsive therapy, lithium, anticonvul-sants, and the serotonin precursor, l-5-hydroxytryptophan. Long-term supportive psychotherapy is almost always indicated to help the patient and his family make painful adjustments to the patient’s chronic disappointments in relationships and employ-ment, frequently made all the more poignant by the illness’ pro-pensity to preserve the patient’s insight as it progresses. This last factor may partially explain the apparently high risk for suicide.
Human experimentation with hallucinogens
The discovery of the effects of LSD in 1943 led to a ﬂ  urry of experi-

mental activity with the drug in humans, at its worst with dubious methodology and indifferent to the protection of human subjects.But the ability of this unique class of drugs to alter perception, cogni-
tion, and affect has prompted a new wave of research with selected hal-lucinogens with regulatory oversight. Studies have examined the safety of peyote in religious use
(21); the psychological effects of psilocybin, 
dimethyltryptamine, and ketamine(22); their use as a tool in modelling 
the pathophysiology of psychosis,(23) and po ssible therapeutic uses.
Hallucinogens have been used as experimental psychoses. 
Vollenweider et al . have found increased metabolic activity in 
the frontal cortex of subjects on the dissociative anaesthetic ketamine,
(24) and in subjects during an experimental psychosis 
from psilocybin, increased serotonin-2 agonist activity.(25) Finally,

from psilocybin, increased serotonin-2 agonist activity.(25) Finally, 
the study of treatment with hallucinogens for psychiatric disorders has cautiously reemerged. In a randomized trial of ketamine for depression, Zarate et al. found that the drug had beneﬁ  ts for a week 
following a single dose.
(26)
Abraham, H.D. (1983). Visual phenomenology of the LSD ﬂ  ashback. 
Archives of General Psychiatry ,40, 884–9.
Abraham, H.D., Aldridge, A.M., and Gogia, P . (1996). The psychopharmacology 
of hallucinogens. Neuropsychopharmacology ,14, 285–98.
Hofmann, A. (1980). LSD: my problem child . McGraw-Hill, New Y ork.
McCarron, M.M., Schulze, B.W., Thompson, G.A., et al. (1981). Acute PCP 
intoxication: incidence of clinical ﬁ  ndings in 1000 cases. Annals of 
Emergency Medicine ,10, 237–42.

 1. McCarron, M.M., Schulze, B.W., Thompson, G.A., et al. (1981). Acute 
PCP intoxication: incidence of clinical ﬁ  ndings in 1000 cases. Annals of 
 2. Johnston, L.D., O’Malley, P .M., Bachman, J.G., et al. (2006). Monitoring 
the future national survey results on drug use, 1975–2005: secondary 
school students , Vol. I (NIH Publication No. 06-5883). National Institute 
on Drug Abuse, Bethesda, MD.
 3. Tabor, B.L., Smith-Wallace, T., and Y onekura, M.L. (1990). Perinatal 
outcome associated with PCP versus cocaine use. American Journal of 
Drug and Alcohol Abuse ,16, 337–48.
 4. Golden, N.L., Kuhnert, B.R., Sokol, R.J., et al. (1987). Neonatal 
manifestations of maternal PCP exposure. Journal of Perinatal 
Medicine ,15, 185–91.

 5. Mattson, M.P ., Rychlik, B., and Cheng, B. (1992). Degenerative and 
axon outgrowth-altering effects of PCP in human fetal cerebral cortical 
cells. Neuropharmacology ,31, 279–91.
 6. Akmal, M., Valdin, J.R., McCarron, M.M., et al. (1981). Rhabdomyolysis 
with and without acute renal failure in patients with PCP intoxication. American Journal of Nephrology ,1, 91–6.
 7. Milhorn, H.T.J. (1991). Diagnosis and management of PCP 
intoxication. American Family Physician ,43, 1290–302.
 8. Poklis, A., Graham, M., Maginn, D., et al. (1990). PCP and violent deaths 
in St. Louis, Missouri: a survey of medical examiners’ cases from 1977 through 1986. American Journal of Drug and Alcohol Abuse ,16, 265–74.
 9. Wright, H.H., Cole, E.A., Batey, S.R., et al. (1988). PCP-induced psychosis:

9. Wright, H.H., Cole, E.A., Batey, S.R., et al. (1988). PCP-induced psychosis: 
eight-year follow-up of ten cases. Southern Medical Journal ,81, 565–7.
10. Campbell, U.C., Thompson, S.S., and Carroll, M.E. (1998). Acquisition 
of oral PCP (PCP) self-administration in rhesus monkeys: effects of dose and an alternative non-drug reinforcer. Psychopharmacology
(Berlin ), 137, 132–8.
11. Misra, A.L., Pontani, R.B., and Bartolomeo, J. (1979). Persistence of PCP 
(PCP) and metabolites in brain and adipose tissue and implications for long-lasting behavioural effects. Research Communications in Chemistry, 
Pathology, and Pharmacology ,24, 431–45.4.2.3.3 disorders relating to use of pcp and hallucinogens

SECTION 4  clinical syndromes of adult psychiatry 490
12. Schultes, R. and Hofmann, A. (1980). The botany and chemistry of 
hallucinogens . Thomas, Springﬁ  eld, IL.
13. Glennon, R.A., Titeler, M., and McKenney, J.D. (1984). Evidence 
for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences ,35, 2505–11.
14. Prisinzano, T.E. (2005). Psychopharmacology of the hallucinogenic 
sage Salvia divinorum .Life Sciences ,78, 527–31.
15. Rickert, VI., Siqueira, L.M., Dale, T., et al. (2003). Prevalence and risk 
factors for LSD use among young women. Journal of Pediatric and 
Adolescent Gynecology ,16, 67–75.
16. Abraham, H.D. (2005). at http://www.drabraham.com/html/hppd.htm
17. Abraham, H.D. and Wolf, E. (1988). Visual function in past users 
of LSD: psychophysical ﬁ  ndings. Journal of Abnormal Psychology ,
97, 443–7.
18. Abraham, H.D. and Duffy, F.H. (1996). Stable quantitative EEG 
difference in post-LSD visual disorder by split-half analysis:

97, 443–7.
evidence for disinhibition. Psychiatry Research and Neuroimaging ,67,
173–87.
19. Lerner, A.G., Gelkopf, M., Skladman, I., et al. (2003). Clonazepam 
treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features. International 
Clinical Psychopharmacology ,18, 101–5.
20. Bowers, M.B. Jr (1977). Psychoses precipitated by psychotomimetic 
drugs: a follow up study. Archives of General Psychiatry ,34, 832–5.
21. Halpern, J.H., Sherwood, A.R., Hudson, J.I., et al (2005). Psychological 
and cognitive effects of long-term peyote use among Native Americans. Biological Psychiatry ,58, 624–31.
22. Gouzoulis-Mayfrank, E., Heekeren, K., Neukirch, A., et al. (2005). 
Psychological effects of (S)-ketamine and N,N-dimethyltryptamine

Psychological effects of (S)-ketamine and N,N-dimethyltryptamine 
(DMT): a double-blind, cross-over study in healthy volunteers. Pharmacopsychiatry ,38, 301–11.
23. Javitt, D.C. and Zukin, S.R. (1991). Recent advances in the PCP model 
of schizophrenia. The American Journal of Psychiatry ,148, 1301–8.
24. Vollenweider, F.X., Leenders, K.L., Scharfetter, C., et al. (1997). 
Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [
18F]ﬂ uorodeoxyglucose (FDG). European Neuropsychopharmacology ,
7, 9–24.
25. Vollenweider, F.X., Vollenweider-Scherpenhuyzen, M.F., Babler, A., et al.
(1998). Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport ,9, 3897–902.
26. Zarate, C.A. Jr, Singh, J.B., Carlson, P .J., et al. (2006). A randomized

trial of an N-methyl- d-aspartate antagonist in treatment-resistant 
major depression. Archives of General Psychiatry ,63, 856–64.
4.2.3.4 Misuse of benzodiazepines
Epidemiology and patterns of use
The rise in benzodiazepine prescribing in the United Kingdom in 
the 1960s and 1970s was a development that followed the previous period of prescribing of barbiturates and other sedatives. Concerns about the obvious toxicity of barbiturates, and previously other sedatives, in overdose, together with knowledge of their dependence-inducing characteristics, led to their replacement with the safer benzodiazepines as the commonly prescribed anxiolytic and hypnotic drugs. Case reports of patients who escalated their dose of benzodiazepines above the recommended dose, and who experi-enced convulsions and confusional states on stopping them, began to appear in the 1970s.

(1,2) In the mid-1970s and onward, regulatory 
bodies in the United Kingdom and United States began to recog-nize the abuse potential of benzodiazepines even in therapeutic doses. Dependence on benzodiazepines was well described in the early literature on the development of these drugs but surprisingly clinical dependence was not reported in the medical literature until the early 1980s.
(3,4) Dependence on therapeutic doses of 
prescribed benzodiazepines is covered in Chapter 6.2.2. In this chapter we are concerned with abuse of and dependence on high doses of benzodiazepines.
The upsurge in the drug epidemic in the 1980s was associated 
with an increase in misuse of hypnosedatives, and in the late 1980s there was a series of reports on the intravenous use of benzodiaze-pines, in particular temazepam.
(5,6) Because benzodiazepines are 
the most commonly prescribed anxiolytics and hypnotics it is not surprising to ﬁ  nd that they are also reported to be commonly mis-

used. However, patterns of misuse vary, from episodic use of non-prescribed medication with up to 15 per cent of young people reporting some experience with benzodiazepines, to continuous high-dose use. Since the mid-1980s there has been a substantial drop in the prescription of benzodiazepines as anxiolytic agents but use as hypnotics has remained relatively steady with the con-centration of long-term use being in the elderly population. Changes in prescribing practices are likely to inﬂ  uence diversion of 
benzodiazepines to the illicit market.
Reports indicate that supra-therapeutic dose misuse and depen-
dence is strongly associated with polydrug and alcohol abuse 
and dependence.
(7,8) This pattern of benzodiazepine misuse

(7,8) This pattern of benzodiazepine misuse 
and dependence is probably much less common than iatrogenic benzodiazepine dependence. However, it presents a substantial prob-lem to many clinicians in primary care and specialist settings. Inparticular, high-dose misuse is likely to be associated with  ‘doctor shopping’ and efforts to extract additional medication on top of that already prescribed. The high doses used present a particular risk because they are often used in combination with other substances such as alcohol, opiates, and stimulants. High-dose use may be inter-mittent in nature (in a ‘binge’ pattern), and not associated with dependence (in which case the initiation of a prescription may change a pattern of intermittent binge use to daily dependent use in a manner that entrenches polydrug use; see the section below on guidelines for management). Drug misusers use benzodiazepines in

a non-dependent fashion for a variety of reasons. For example, ben-
zodiazepines may be used to enhance the effect of other drugs (such as boosting the euphoria with heroin), or to alleviate unwanted effects from other drugs (to ‘cushion’ the ‘come-down’ from cocaine), or to help alleviate withdrawal symptoms when drugs such asheroin are unobtainable, or in attempts at self-detoxificationfrom other drugs. Misuse of benzodiazepines may also arise from injudicious patterns of prescribing for the treatment of alcohol dependence, or from attempts at self-treatment for alcohol depen-dence. Some drug users will also develop a dependent pattern of use of benzodiazepines in their own right. Benzodiazepine dependence may be a factor contributing to poor outcome for patients who are attempting opiate detoxiﬁ  cation.
High-dose use is associated with substantial tolerance to the

High-dose use is associated with substantial tolerance to the 
sedating effects of the medication but some of the other effects may not be equivalently protected by tolerance. Thus, some individuals may consume extraordinarily high doses, and not appear sedated, but experience profound amnesia for their actions. Such effects of

491
amnesia may also be associated with the reported high rates of 
risk-taking behaviour, and amnesia may be more pronounced in injecting benzodiazepine users, although there are no good data to conﬁ  rm this.
The potential of different benzodiazepines 
for misuse and dependence
In view of the frequency of prescribing of benzodiazepine drugs, it 
is an important question as to whether some benzodiazepines are more likely to be misused, or to lead to dependence, than others. The similarities between different benzodiazepines are much greater than the differences. Patients may maintain that they need a speciﬁ  c 
named benzodiazepine, but there is marked cross-tolerance, and patients changed to an equivalent dose of a different benzodiaze-pine under double-blind conditions show almost completecross-dependence (i.e. no difference in withdrawal symptoms from those whose medication has been unchanged).
(9) However, this

(9) However, this 
cross-dependence was shown for patients who were alreadybenzodiazepine dependent. It is possible that the properties ofcertain benzodiazepines lead to a stronger motivation for peopleto desire their effects, to escalate the dose, and to persist withtheir use.
Factors that have been considered to inﬂ  uence the liability to 
misuse and development of dependence include the relative potency of the drug, and its elimination half-life.
(10) Triazolam, a very short-

acting benzodiazepine prescribed for insomnia, was withdrawn from the British market following concerns about the severity of rebound anxiety experienced even after a single dose. Triazolam is a very potent benzodiazepine that binds very readily to benzodiazepine receptors, and experience with its use suggested that it had a more euphoriant effect than other benzodiazepines, resulting in greater potential for misuse and for the development of dependence. Other benzodiazepines that have high potency and have caused concern include flunitrazepam and lorazepam. Flunitrazepam is relatively rarely prescribed in the United Kingdom, but frequently reported as one of the most common benzodiaze-pines misused in many European countries and in Australia. It is not marketed in the United States. Concerns about its availability on the illicit market continue.

(11,12)  It has attracted media attention 
as a drug used to facilitate ‘date rape’; it is unclear why this particu-lar benzodiazepine should have this image, although it is a potent drug. Lorazepam, also a potent benzodiazepine, is much more widely prescribed in the United Kingdom, and alprazolam is used in the United States. Some studies suggest that lorazepam and alprazolam may be associated with an earlier and more difﬁ  cult 
withdrawal process than diazepam.
(9,13)  In one European study, 
triazolam and lorazepam were found to feature more highly among individuals dependent on high doses of benzodiazepine drugs than among those dependent on low or ‘therapeutic’ doses.
(14) In

(14) In 
summary, it appears that potency is a contributory factor in the abuse and dependence-inducing potential of benzodiazepine drugs. However, this picture is somewhat complicated by the fact that drugs such as lorazepam tend to have been marketed at higher equivalent doses than some other benzodiazepines. The elimina-tion half-life inﬂ  uences the nature of withdrawal; if it is short, 
withdrawal symptoms appear more rapidly and may appear more severe, although withdrawal of more insidious onset in longer-acting benzodiazepines may be just as problematic.As well as properties of the drugs themselves, the abuse potential

of different benzodiazepines is also associated with broader pre-scribing patterns which affect the potential for diversion to illicit market. Diazepam and temazepam have been the most widely pre-scribed benzodiazepines in the United Kingdom, and are therefore the most likely to be obtained by drug users and problem drinkers. Drugs such as clonazepam which tend to be prescribed much less widely, and generally for epilepsy rather than for anxiety or insomnia, seem infrequently to raise concerns about misuse
(10) but 
are frequently requested as the treatment of choice for those who are both epileptic and drug dependent. In other parts of Europe where ﬂ  unitrazepam is more commonly prescribed, there 
are reports of its high levels of misuse among the illicit drug-using population.
The potential for misuse by injecting
Over time, there have been reports of misuse of various benzodiaz-epines by injection.
(7) A number of factors have inﬂ  uenced this

(7) A number of factors have inﬂ  uenced this 
practice. These include the availability of the drug, its short-acting nature, and also the formulation of the drug. In the 1980s temaze-pam was marketed as a liquid-ﬁ  lled capsule, which enabled easy 
extraction of the contents to put into a syringe for injecting. The later gel formulation was also injected, by heating to liquidize the gel, resulting in very damaging injecting complications. Some medications that come in easily soluble form can also be converted into a form for injecting, such as liquid diazepam.
The injection of benzodiazepine drugs is associated with sub-
stantially more harmful drug misuse in a number of respects,
(15)
with increased rates of reported sharing of injecting equipment,(9,16)
increased risks of overdose, and poorer general health.(8)
Evidence-base for management of

(15)
Evidence-base for management of 
benzodiazepine misuse
The literature on management of ‘ordinary dose’ benzodiazepine 
dependence, relating mainly to patients prescribed benzodiazepines for treatment of psychiatric disorders, is far more extensive andsystematic than that concerning illicit drug users. At the time of writing, there are no meta-analyses or indeed well-conducted ran-domized controlled trials speciﬁ  cally addressing this problem. In

practice, the applicability of the ‘ordinary dose’ dependence litera-ture is affected not only by clinical differences, but also by concerns about abuse and diversion of prescribed supplies by illicit drug users. So far, no clear guidelines for management have been pro-duced, and the management principles covered in the section below are based on expert clinical consensus statements: these involve some extrapolation from the ‘ordinary dose’ benzodiazepine depen-dence literature, and some from established evidence-based princi-ples for management of misusers of other drugs such as opiates.
(17)

(17)
For example, unlike the established evidence that supervised substi-tute prescribing of methadone reduces injecting in intravenous her-oin users, there is no clear evidence that substitute prescribing of benzodiazepines reduces injecting behaviour in injecting misusers of these drugs. Nevertheless, prescribing of oral benzodiazepines with daily supervised consumption is sometimes instituted for this group of patients, especially if they are already established in super-vised treatment for concurrent intravenous heroin use (see section on concurrent opioid dependence below).4.2.3.4 misuse of benzodiazepines

SECTION 4  clinical syndromes of adult psychiatry 492
Guidelines for management of misuse of 
non-prescribed benzodiazepines
These are a complex group of patients to manage and in general 
such patients should be referred for specialist assessment.
Assessment should attempt to conﬁ  rm evidence for benzodiazepine 
dependence. Assessment over a number of visits should involve obtaining urine specimens to determine objectively the regularity (or intermittent nature) of benzodiazepine consumption. Part of the initial assessment process should identify underlying psychiat-ric disorders that may have been the trigger for a doctor initiating a prescription or for the patient obtaining drugs for the purpose of self-medication. High levels of psychiatric morbidity have been found among samples of patients with severe benzodiazepine dependence.
(18) The commonest conditions are probably anxiety

(18) The commonest conditions are probably anxiety 
disorders for which anxiolytics have been prescribed injudiciously; however, in some instances major depressive disorders may be treated or self-medicated with benzodiazepines. Thorough assess-ment should explore for evidence of major depression and if iden-tiﬁ ed, consideration should be given to the use of antidepressant 
medication combined with cognitive behavioural therapy.
Treatment

Treatment
In the presence of polydrug abuse or dependence, caution needs to be exercised about initiating a prescription for benzodiazepines (see section on opioid drug users). Where dependence is estab-lished, dose titration should aim to ameliorate withdrawal symp-toms rather than to match the large doses of medication that the patient reports consuming. Long-acting benzodiazepines such as diazepam are preferred (Chapter 6.2.2), and doses should rarely exceed 40 to 60 mg daily. Where large doses are prescribed these should ideally be dispensed on a daily pick-up basis from the com-munity pharmacist. The prescribing doctor should avoid succumb-ing to pressure from the patient to increase the dose without a 
thorough dose assessment and evidence of withdrawal symptoms. 
Prescriptions issued on a routine ‘repeat’ basis should be avoided, 
and the patient should be informed that lost medication will not be

and the patient should be informed that lost medication will not be 
replaced. Requests for replacement medication or additional medi-
cation should encourage the doctor to review the overall care plan and to consider reducing and stopping the benzodiazepine pre-
scription. Virtually all benzodiazepine prescriptions should be time 
limited and part of a detoxiﬁ  cation plan with gradual reduction 
over a clearly stated and negotiated time period. Alternatively, 
inpatient detoxiﬁ  cation, perhaps with longer admissions, may be 
the best course of action where reduction regimens fail in the com-

munity setting. Reduction regimens with benzodiazepines are very variable and many clinicians opt for a very gradual withdrawal with small dose reduction at wide intervals. There is no evidence to indi-cate that such a gradual approach is any more effective than 20 to 25 per cent reductions over a shorter, more clearly deﬁ  ned time 
(such as 6 weeks). Carbamazepine can also be effective in amelio-rating withdrawal symptoms and in seizure prevention, and may be used as an adjunct in withdrawal management in high-dose benzodiazepine dependence,
(19) though drug interactions need to 
be considered for patients who are also prescribed opioid substi-tute drugs for treatment of heroin dependence (see section on concurrent benzodiazepine and opioid dependence).Special considerations for managing 
concurrent benzodiazepine and alcohol dependence

There are high reported rates of alcohol dependence among the 
homeless, and there are substantial reports of benzodiazepine abuse and dependence in this population also. Cross-tolerance between benzodiazepines and alcohol permits individuals who are alcohol dependent to tolerate high doses of benzodiazepines. Patients may be prescribed benzodiazepines to manage alcohol withdrawal, but injudicious prescribing that is not targeted towards the manage-ment of alcohol withdrawal symptoms may result in iatrogenic benzodiazepine dependence.
The extensive research on pharmacological interventions
for management of alcohol withdrawal in alcohol-dependent patients has been examined in a meta-analysis by Mayo-Smith, who subsequently produced a systematic review with treatment guidelines.
(20) This review supports the use of benzodiazepines

as the treatment of choice for managing withdrawal symptomsfor patients whose symptoms are of sufﬁ  cient severity to warrant 
medication, and is consistent with a more recent Cochrane review.
(21) However, carbamazepine is established as an accep-
table alternative to benzodiazepine drugs in treatment of alcohol withdrawal, and is effective both in reducing withdrawal symptoms and in seizure prevention.
(17) Agents such as clomethiazole and
the barbiturate phenobarbital, are less well-supported by controlled trials than benzodiazepines, and carry higher risks of adverse effects.
The potential for misuse of benzodiazepines must be considered

The potential for misuse of benzodiazepines must be considered 
in alcohol-dependent patients. However, this is not an adequate reason for avoiding the use of benzodiazepines in the management of withdrawal in view of their superiority in effectiveness, and pos-sibly in potential for harmful misuse, over other treatments. Benzodiazepines with a slower onset of action such as chlordiaz-epoxide, appear to have less potential for misuse. The prolonged use of benzodiazepines in withdrawal is rarely necessary or helpful, and evidence for beneﬁ  ts of ‘substitute prescribing’ of benzodiaze-
pines for alcohol users in the longer term is lacking. Use of benzo-
diazepines to manage phobic and anxiety disorders associated with 
alcohol dependence should be avoided. For alcohol-dependent patients with a history of benzodiazepine misuse, especially where the patient wishes to avoid further benzodiazepine use, manage-ment of withdrawal using carbamazepine alone should be explored.

Special considerations for managing 
concurrent benzodiazepine and opioid drug dependence
Currently there is no evidence base for long maintenance prescrib-
ing of benzodiazepines for those who are high-dose injecting polydrug abusers. However, this intervention has not been subject to any structured evaluation and merits further study in the face of the difﬁ  culties of managing such patients. There are two particular 
areas of concern in managing opioid drug users who also misuse benzodiazepines. The ﬁ  rst is the potential for toxicity and overdose 
when combining illicit or prescribed opioid drugs with benzodiaz-epines, particularly because of the sedative and respiratory

493
depressant effect of both. Two studies comparing the effects of 
benzodiazepine use in conjunction with either methadone or buprenorphine treatment have reported higher subjectively reported opioid toxicity symptoms
(22) and greater peak effects on 
objectively assessed performance measures(23) for patients on

objectively assessed performance measures(23) for patients on 
methadone than for patients on buprenorphine. Where substitute prescribing for heroin or other opioid drug dependence is to be undertaken, the patient needs clear information about the effects of combining opioid and benzodiazepine drugs. Close supervision of prescribed medication (such as daily supervised consumption in the clinic or pharmacy) should be maintained in the early stages of treatment. As many opioid drug users use benzodiazepines some-what erratically, for example as a substitute when heroin is not available, then stabilization on either methadone or buprenorphine as a regular dose may allow them to stop benzodiazepine use with-out any other intervention. Initiation of any prescribing interven-tion addressing benzodiazepine dependence is usually best delayed until it is clear that dependent use has continued despite well-established treatment for opioid dependence. The second area of

concern is the potential poor prognosis of opioid withdrawal pro-
grammes for patients with concurrent benzodiazepine dependence. Opioid withdrawal symptoms may be more pronounced in patients with both problems, and treatment protocols may need to be adjusted to address this.
(24)
There is a valuable role for benzodiazepines, and a need for vigilance and care in their use, as well as active recognition and management of those who are dependent. However, there is a need for greater awareness of the risks of polydrug dependence with misuse of high doses of benzodiazepines in conjunction with both alcohol dependence and opiate dependence. Caution needs to be used in assessing patients, and benzodiazepine prescribing should be restricted to those where there is clear evidence of dependence.
The risk of synergistic effects with other drugs and consequent 
overdose should be explained to all patients who are identiﬁ  ed

overdose should be explained to all patients who are identiﬁ  ed 
as being involved in such behaviour. Community detoxiﬁ  cation
or inpatient detoxification is the best option based on theevidence of available research and evaluation of currentinterventions.
Seivewright, N. (2000). The case for other substitute drugs. Community 
treatment of drug misuse: more than methadone , pp. 49–81. Cambridge 
University Press, Cambridge, UK.
Lingford-Hughes, A.R., Welch, S., and Nutt, D. (2004). Evidence-based 
guidelines for the treatment of substance misuse, addiction and 
comorbidity: recommendations from the British Association for Psychopharmacology. Journal of Psychopharamacology ,18, 293–335.
 1. Woody, G.E., O’Brien, C.P ., and Greenstein, R. (1975). Misuse and 
abuse of diazepam: an increasingly common medical problem. International Journal of Addiction ,10, 843–8.

 2. Bliding, A. (1978). The abuse potential of benzodiazepines with special 
reference to oxazepam. Acta Psychiatrica Scandinavia Supplementum ,
274, 111–16. 3. Petursson, H. and Lader, M.H. (1981). Benzodiazepine dependence. 
British Journal of Addiction ,76, 133–45.
 4. Hallstrom, C. and Lader, M. (1981). Benzodiazepine withdrawal 
phenomena. International Pharmacopsychiatry ,16, 235–44.
 5. Farrell, M. and Strang, J. (1988). Misuse of temazepam. British Medical 
Journal ,297, 1402.
 6. Ruben, S.M. and Morrison, C.L. (1992). T emazepam misuse in a
group of injecting drug users. British Journal of Addiction ,
87, 1387–92.
 7. Strang, J., Seivewright, N., and Farrell, M. (1992). Intravenous and

 7. Strang, J., Seivewright, N., and Farrell, M. (1992). Intravenous and 
other novel abuses of benzodiazepines: the opening of Pandora’s box? British Journal of Addiction ,87, 1373–5.
 8. Ross, J., Darke, S., and Hall, W. (1997). Transitions between routes 
of benzodiazepine administration among heroin users in Sydney. Addiction ,92, 697–705.
 9. Murphy, S.M. and Tyrer, P . (1991). A double-blind comparison of the 
effects of gradual withdrawal of lorazepam, diazepam and bromazepam in benzodiazepine dependence. The British Journal of Psychiatry ,
158, 511–16.
10. Tyrer, P . (1993). Pharmacological differences in the dependence 
potential of benzodiazepines. In Benzodiazepine dependence
(ed. C. Hallstrom), pp. 77–90. Oxford University Press, Oxford.
11. Simmons, M.M. and Cupp, M.J. (1998). Use and abuse of 
ﬂ unitrazepam. Annals of Pharmacotherapy ,32, 117–19.

12. Woods, J.H. and Winger, G. (1997). Abuse liability of ﬂ  unitrazepam. 
Journal of Clinical Psychopharmacology ,17(Suppl. 2), 1S–57S.
13. Rickels, K., Case, W.G., Schweizer, E.E., et al. (1986). Low dose 
dependence in chronic benzodiazepine users; a preliminary report on 119 patients. Psychopharmacology Bulletin ,22, 415–17.
14. Martinez-Cano, H., Vela-Bueno, A., De Iceta, M., et al. (1996). 
Benzodiazepine types in high versus therapeutic dose dependence. Addiction ,91, 1179–86.
15. Darke, S., Hall, W., Ross, M., et al. (1992). Benzodiazepine use and HIV 
risk-taking behaviour among injecting drug users. Drug and Alcohol 
Dependence ,31, 31–6.
16. Klee, H., Faugier, J., Hayes, C., et al. (1990). AIDS-related risk 
behaviour, polydrug use and temazepam. British Journal of Addiction ,
85, 1125–32.

17. Lingford-Hughes, A.R., Welch, S., and Nutt, D. (2004). Evidence-
based guidelines for the treatment of substance misuse, addiction 
and comorbidity: recommendations from the British Association for 
Psychopharmacology. Journal of Psychopharamacology ,18, 293–335.
18. Busto, U.E., Romach, M.K., and Sellers, E.M. (1996). Multiple 
drug use and psychiatric comorbidity in patients admitted to the 
hospital with severe benzodiazepine dependence. Journal of Clinical 
Psychopharmacology ,16, 517.
19. Denis, C., Fatseas, M., Lavie, E., et al. (2006). Pharmacological 
interventions for benzodiazepine monodependence management in outpatient settings. Cochrane Database of Systematic Reviews ,
(3), CD005194.
20. Mayo-Smith, M.F. (1997). Pharmacological management of alcohol

20. Mayo-Smith, M.F. (1997). Pharmacological management of alcohol 
withdrawal: a meta-analysis and evidence-based practice guideline. The Journal of the American Medical Association ,278, 144–50.
21. Ntais, C., Pakos, E., Kysaz, P ., et al. (2005). Benzodiazepines for
alcohol withdrawal. Cochrane Database of Systematic Reviews , (3), 
CD005063.
22. Nielsen, S., Dietze, P ., Lee, N., et al. (2007). Concurrent buprenorphine 
and benzodiazepines use and self-reported toxicity in opioid substitution treatment. Addiction ,102, 616–22.
23. Lintzeris, N., Mitchell, T.B., Bond, A., et al. (2006). Interactions on 
mixing diazepam with methadone or buprenorphine in maintenance patients. Journal of Clinical Psychopharmacology ,26, 274–83.
24. de Wet, C., Reed, L., Glasper, A., et al. (2004). Benzodiazepine 
co-dependence exacerbates the opiate withdrawal syndrome. Drug and 
Alcohol Dependence ,76, 31–5.4.2.3.4 misuse of benzodiazepines

SECTION 4  clinical syndromes of adult psychiatry 494
4.2.3.5 Disorders relating to the use 
of ecstasy and other ‘party drugs’
Participation in the dance music/rave scene has been associated 
with an ever-growing range of primarily stimulant and hallucino-genic drugs since its inception in the Balearic Islands in the mid-1980s. The last two decades have seen the globalization of the dance music scene and the gradual adoption of these and other drugs by mainstream drug using populations. Although ‘Ecstasy’ ( MDMA ,
3,4-methylenedioxymethamphetamine) was the archetypical dance drug inducing both stimulant and empathogenic effects, dance drug use is polydrug use with cocaine, amphetamine, nitrates, ketamine, and GHB all being common.
(1) The use of this diverse 
group of drugs is now no longer conﬁ  ned to either young adults 
or the dance ﬂ  oor with use common for example, at house parties

or the dance ﬂ  oor with use common for example, at house parties 
or other more intimate social gatherings.(2) Although not typically 
identiﬁ  ed as dance drugs, alcohol and cannabis are of course highly 
prevalent among this group.
Ecstasy 
(3,4-methylenedioxymethamphetamine)
Incorrectly termed a designer drug (a drug whose chemical 
structure is modiﬁ  ed to avoid being included within a list of drugs/
chemical structures prohibited by legislation), MDMA was ﬁ  rst 
synthesized in 1912 by Merck Pharmaceuticals. It was never marketed and remained largely ignored until the 1950s when the United States Army explored its military potential. It was not until the late 1960s and early 1970s however that drug users on the west coast of America began to popularize its recreational use along with MDA (methylenedioxymethamphetamine).

Although MDMA may claim its place as the mother of dance 
drugs and possessor of the best branding in terms of name, MDMA is only one of a large number of synthetic amphetamine type drugs possessing varying degrees of stimulant, hallucinogenic, andempathogenic effects that are used within the dance scene. 
Characterized by its stimulant and prosocial effects the sought after 
experiences of disinhibition, euphoria, energy, and empathy are ideally suited to the ‘dance scene’ where energetic and prolonged dancing is commonplace. Indeed it may be that dancing offsetsthe psychomotor agitation that stimulants can induce or that MDMA-like drugs may enhance enjoyment and ability to dance to dance music. In the United Kingdom MDMA is classiﬁ  ed as a Class 
B drug.
Preparations, purity, and routes of use

B drug.
MDMA is most commonly taken orally though it may be snorted or injected. MDMA is most commonly sold as branded tablets (‘pills’), with different tablets being identiﬁ  ed by an imprinted logo 
(for example of a cartoon character, car manufacturer, or animal), but may also be found as capsules or powder. The average dose of an ecstasy tablet containing MDMA is about 70 mg (range 50–150 mg). The cost has reduced markedly over the last 20 years from 
£20/tablet in 1985 to as little at 50 pence/tablet when bought in bulk (typical price in the United Kingdom for a single tablet would be 2–5).
(3)
Because of the illicit nature of MDMA production, variation in

(3)
Because of the illicit nature of MDMA production, variation in 
precursor availability, and the large number of possible synthetic pathways for its production, tablets sold as ecstasy may contain a wide range of substances other than MDMA. In the United Kingdom and Europe especially in the 1990s, ecstasy tablets were often found to contain substances (usually psychoactive) other than MDMA. These included analogues of MDMA, such as methylenedioxyamphetamine ( MDEA ), N-methyl-1-(1,3-benzo-
dioxol-5-yl)-2-butanamine ( MBDB ), and methylenedioxyethyl-
amphetamine ( MDEA ), or combinations of stimulants such as 
ephedrine or amphetamine and hallucinogens such as LSD or ketamine.
(4) While these other psychoactive substances may 
be marketed as distinct substances with their own branding (e.g. 4-Bromo-2, 5-dimethoxyphenethylamine sold as 2CB and 4 MTA as ‘ﬂ atliners’) more commonly they and the MDMA analogues

be marketed as distinct substances with their own branding (e.g. 4-Bromo-2, 5-dimethoxyphenethylamine sold as 2CB and 4 MTA as ‘ﬂ atliners’) more commonly they and the MDMA analogues 
MDEA, MBDB, and MDA, which broadly share the effects of MDMA, are sold under the generic term ‘ecstasy’ . More recent evi-dence would suggest that the proportion of tablets sold as ecstasy that contains MDMA in the United Kingdom is very high, with purity levels of 80–90 per cent not being uncommon.
(5)
Pill testing

(5)
Some users utilize various pill testing methods (such as the Marquis test which gives colorimetric result by mixing the substance with a reagent) and websites (www.EcstasyData.org) which provide the contents of different pills following more elaborate analytical methods. Although it may be the case that these approaches may have some role in getting users to consider risks and promote the uptake of harm reduction practices, it is only on very few occasions that such methods have identiﬁ  ed potentially far riskier psychoac-
tive contents such as paramethoxyamphetamine (PMA).
(6) In such 
cases, early warning through such websites may be potentially help-ful. However, even with more  sophisticated analytic processes (e.g. 
GMS, HPLC), knowing the content of your tablet never guarantees the user a positive experience and does not guarantee that they will not experience severe adverse effects.
(4) In addition, most ecstasy-

related deaths have involved tablets containing MDMA. Most deaths have not been related to dose and would have been unpre-dictable from knowing the content of the tablet.
(3)
Prevalence and patterns of ecstasy use
British population studies show that 54 per cent of 20- to 22-year-olds have been offered ecstasy at some time and 15 per cent have tried it at least once.
(7) The prevalence of use appears higher in 
those associated with the dance music drug scene with over 90 per cent reporting ever use. Similar ﬁ  ndings have been reported from 
Europe,
(8) Australia,(9) and the United States.
The typical pattern of use in the United Kingdom and Europe is 
one to four tablets a night, though many users will often consume larger number of tablets during a binge session especially when holidaying in summer dance resort destinations. Regular users will use between once or twice a week to once every fortnight, though

there has been increasing recognition of a minority of users who 
take very large numbers of tablets (20 or 30) over a single session,

495
or with the availability of very cheap ‘pills’ extended periods of 
low-level daily use. Ecstasy, especially within the context of dance clubs is rarely taken in isolation and polydrug use is the norm, with different adjunctive substances taken at different times over the course of a night.
(1) For example, alcohol is taken with ecstasy at 
the beginning of the night to get a stronger/better high.(10) Cocaine,

the beginning of the night to get a stronger/better high.(10) Cocaine, 
amphetamines, and/or additional ecstasy tablets are taken to main-tain arousal and a state of alertness (the MDMA enactogenic effects fade away in 2–4 h). Finally depressants such as cannabis, alcohol, benzodiazepines, and more rarely opiates, may be taken in the last part of the night to calm down before going home, since the untoward after-effects of ecstasy (namely irritability, insomnia, and restlessness) may persist well beyond its ‘pleasurable’ effects. With a chronic high dosage, ecstasy users develop tolerance and experience a decrease in the desired effects over time, which could lead to exploration of use of other stimulants and hallucinogens.
(1)
Physical effects and complications

(1)
Physiologically sympathomimetic properties similar to amphet-amine predominate including tachycardia, anorexia, increased respiratory rate, blood pressure, increased motor activity, tremor, mydriasis, increased temperature, and sweating. Jaw tightening (bruxism), xerostomia, teeth grinding with molar erosion, may also be seen (see Table 4.2.3.5.1). Sleep architecture modiﬁ  cation
(11)
and sexual activity alteration(12,13)  have also been described.
After MDMA intake a number of untoward effects may commonly 
occur including nausea, vomiting, diarrhoea, tachycardia, and palpitations. Pathologies less commonly seen include arrhythmias, hypertension as well as potentially life-threatening, metabolic acido-sis, cerebral haemorrhages, convulsions, coma, rhabdomyoloysis, thrombocytopenia, disseminated intravascular coagulation, SIADH, acute kidney failure, acute liver failure, dehydration, and malignant hyperthermia.
(14–18)

(14–18)
Hyperthermia although enhanced by exertional activity and 
poorly ventilated environments may be somewhat independent from the setting in which the drug is taken, with MDMA having thermal dysregulation effects in its own right. Dehydration is com-mon and thirsty clubbers naturally tend to replace body ﬂ  uids lost 
during sweating sensibly with fruit juices, other isotonic ﬂ  uids or water, or less sensibly but quite commonly with alcohol. Very 
rarely excessive intake of hypotonic ﬂ  uids, coupled with an increase in vasopressin levels, has led to the occurrence of lethal hyponatraemia.
(19) Deaths as a result of SIADH are very rare
but can be fatal in association with excessive hypotonic ﬂ  uid
consumption with MDMA potentially impairing judgement or stimulating repetitive compulsive behaviours. In normal subjects who take ecstasy and do not develop SIADH there does appears to be an increase in both ADH and oxytocin levels,
(20) the latter

(20) the latter 
perhaps responsible for the drug’s prosocial effects. MDMA is a potentially damaging cardiac stimulant;
(21) with reports suggest-
ing long-term MDMA use may possibly lead to a fenﬂ  uramine-
like valvular heart disease condition. All users of ecstasy develop a (mild, in most cases) serotonin syndrome after acute drug intake.
(13,22)  Unfortunately although be ing reported by almost 
half ecstasy users, Verheyden and Henry(23) found that concerns 
about physical health are not perceived as important as concerns about mental health.
(23)
MDMA psychological effects and problems 
(see Table 4.2.3.5.1, adapted from Liester et al .(24))
Being structurally related to both amphetamine and mescaline, 
‘empathogens’ or ‘entactogens’(25) like MDMA possess both stimu-

lant and hallucinogenic properties which allow them to be discrim-inated from other related substances. After MDMA ingestion, enhanced mood, increased energy, openness, heightened sensory perception, and mild perception alterations are reported
(15,17)
(Table 4.2.3.5.1).
MDMA is described as evoking ‘an easily controlled altered state 
of consciousness with emotional and sensual overtones’ ,(26)

(15,17)
with the substance’s appeal resting in its ‘dramatic and consistent ability to induce in the user a profound feeling of attachment and connection’ . With this in mind it is perhaps not surprising that the Los Angeles dealer who coined the street name ‘ecstasy’ for MDMA would have preferred the name ‘empathy’ but he did not feel that his typical customer would know what it meant. It was also these qualities that led to the enthusiasm of a small number of physicians and therapists in the United States to explore its use within a clini-cal psychotherapeutic setting and more recently led to its approval as a research agent in the treatment of PTSD.
(27)
Acute psychological problems associated with 
MDMA use
There have been reports of acute episodes of anxiety, panic, para-

(27)
MDMA use
noia, and rarely brief psychotic episodes following consumption of MDMA by some users. Many users of MDMA report ‘midweek blues’ , with some individuals reporting clinically borderline levels of depression in the days following MDMA
(28) which could reﬂ  ect 
depletion of serotonin following the acute elevation that follows ingestion of MDMA. This could be seen as a parallel to the ‘crash’ reported after abstinence of cocaine use or as a hangover effect from all night dancing, excessive alcohol, and minimal sleep. Although depression, anxiety, and mood ﬂ  uctuations attributed 
to ecstasy are reported to be strongly related to the number of occasions of MDMA use,
(29,30)  Morgan et al.31 found that higher 
depression scores among current heavy ecstasy users, in compari-son to drug-naïve and polydrug controls, were no longer signiﬁ  -

cant after treating cannabis use as a covariate.Table 4.2.3.5.1  Psychological and physical effects of MDMA
Physical Psychological
Increase in physical and emotional energy Relaxation/euphoria
Dilated pupils, dry mouth Feelings of well-beingTachycardia, hypertension, increased 
 respiratory rateEnhanced closeness and 
sociability
Increased sweating, dehydration Heightened perceptual awarenessIncreased motor activity, tremor DisinhibitionBlurred/double vision Increased response to touch/
empathy
Anorexia, nausea, weight loss Anxiety/panic/paranoiaTeeth grinding, jaw clenching Agitation and restlessness4.2.3.5 disorders relating to the use of ecstasy and other ‘party drugs’

SECTION 4  clinical syndromes of adult psychiatry 496
Other consequences of use
(a)  Neurotoxicity and evidence for 5-HT disruption in humans 
(see Table 4.2.3.5.2)
Although, in humans, the relationship between MDMA intake, 
putative 5-HT neurotoxicity, and persistent functional conse-quences is somewhat controversial,
(32) the average single dose size 
consumed by humans approaches levels found to be neurotoxic in animals.
(10) Core ambient temperature and hydration status 
have been implicated as key factors in the development of neurotoxicity.
(13)
Although Colado et al.33 suggested that MDMAs ability to pro-

(13)
duce neurodegeneration of dopamine nerve endings is open to debate, MDMA is generally considered to be a selective 5-HT neu-rotoxin. After administration of MDMA, animals have reduced levels of 5-HT, 5-hydroxyindole acetic acid, and tryptophan hydroxylase. Abnormal 5-HT regrowth has been reported after MDMA-induced damage with a decrease in 5-HT terminal den-sity, suggestive of a ‘chemical axotomy’ . Pathological investigations suggest that 5-HT nerve terminals arising from the dorsal raphe 
nucleus are speciﬁ  cally involved. Duration and magnitude of these 
neurotoxic effects are dose dependent and are followed by differ-ential rates of recovery, with 5-HT damage persisting for up to a year in the rat, and dopaminergic damage for up to 3 years in the

neurotoxic effects are dose dependent and are followed by differ-ential rates of recovery, with 5-HT damage persisting for up to a year in the rat, and dopaminergic damage for up to 3 years in the 
rhesus monkey. These changes appear to be species speciﬁ  c with 
primates being more sensitive to the neurotoxic damage than rodents.
Markers for 5-HT damage may be sought either by direct 
assessment of metabolite levels or indirectly by assessing those functions thought to be dependent on an intact 5-HT system (see Table 4.2.3.5.2). MDMA users may show reduced brain 5-HTT (serotonin transporter) levels; there might be an association between degree of MDMA exposure and degree of reduction in 5-HTT ligand binding.
(34)
Further evidence for disruption of the 5-HT system comes 
from blunted neuroendocrine responses (cortisol and prolactin) to d-fenﬂ  uramine in former MDMA users;
(13) from cognitive distur-

(34)
bances in former MDMA users and from PET studies showing a decrease in a structural component of 5-HT neurones.
(b)  Neuropsychological impairment and psychiatric 
presentation of ecstasy users
MDMA users as a group demonstrate a range of cognitive deﬁ  -
cits in comparison to alcohol users, non-drug controls,and MDMA-naïve polydrug controls, including cannabis users.
(31,35)  Although the issue is somewhat controversial the most consistent neuropsyc hological ﬁ  nding in former MDMA 
users is a deﬁ  cit in verbal memory under both immediate- and 
delayed-recall conditions.(36) Deﬁ  cits in other areas of cognitive 
function, such as verbal fluency, executive function, impulse
control, reaction time, and processing speed have been reportedas well.

(31) Evidence for attentional deficits varies depending
on the task employed.(37) MDMA use may be associated with lon-
ger visual scanning times, reaction times, or planning times. Interpretation of these data is somewhat complicated by the fact that MDMA users typically use other drugs which may exert inde-pendent or interactive effects on cognitive performance.
(37)
MDMA intake may put users at signiﬁ  cant risk for developing 
psychiatric problems,(23) although some have suggested that this 
may occur only in vulnerable individuals.(39) Studies suggest that 
ecstasy users may report both childhood emotional/physical abuse
(40) and history of  familial depression, anxiety, and panic 
attacks(41) more frequently than ecstasy-naïve controls.
Thus although fraught with confounders, especially other

drug use and premorbid functioning, there does appear to bean association between MDMA use and increased rates ofanxiety,
(24) panic, major depressive disorder,(38) prolonged
depersonalization, psychosis, ﬂ  ashbacks, and even craving for 
chocolate.
(c) Depression and its management in ecstasy users
In the case of a patient presenting with psychological problems who has a history of MDMA use, the crucial assessment issues are the identiﬁ  cation of any premorbid disorders, where in the cycle of

In the case of a patient presenting with psychological problems who has a history of MDMA use, the crucial assessment issues are the identiﬁ  cation of any premorbid disorders, where in the cycle of 
use/post use they are, and the persistence of any symptoms beyond a 2–4 week period following cessation of use. As with amphet-amine use, in the days after taking MDMA there is a period char-acterized by symptoms attributable to monoamine depletion and subsequently repletion. A period of acute 5-HT depletion due to vesicular monoamine depletion (Tuesday blues), is likely to be the most potent cause for the relative reduction in monoamine neu-rotransmitters. Repeated use of MDMA over several days will be associated with markedly diminished effects. Recovery is delayed further by inhibition of the rate-limiting enzyme (tyrosine hydrox-ylase in the case of MDMA) and the relative absence especially in chronic users, of a good source of monoamine precursors follow-

ing stimulant-induced anorexia and malnutrition. It is likely that, as with other stimulant drugs, including cocaine, a period of 
extended but less intense withdrawal symptoms (mood, sleep) may be seen with persistent abstinence which may take weeks or months to recede and are associated with the more gradual rever-sal of neuroadaptive changes in dopaminergic receptor sensitivity/expression.
(42)
History taking should speciﬁ  cally endeavour to identify any pre-
existing/persistent depressive/other disorders and to ascertain the functionality of the use of MDMA and the consequences on under-lying mood and functioning in days following use. Antidepressant treatments should usually not be commenced until 2–4 weeks after cessation of MDMA use in order to allow for reassessment and conﬁ  rmation of any disorder. In addition, resolution of symptoms

with cessation of use may also act as powerful reinforcer of contin-ued abstinence if an individual’s mood recovers. Reassessment and treatment where necessary, is important since being depressed is associated with an enhanced initial response to stimulant drugs and higher relapse risk.Table 4.2.3.5.2  Clinical signs of intoxication with amphetamine
Physical Psychological Behavioural
Elevated P , BP , 
 temperatureEuphoria/energized Motor hyperactivity
Increased respiratory 
 rateAnxious/irritable Restless/twitching
Sweating/dehydrated Rapid thoughts Talkative, pressured speech
Dilated pupils Paranoia AggressiveTremor/shakiness Perceptual disturbance Stereotyped movements

497
In prescribing an antidepressant to a client with a previous
history of MDMA use, conﬁ  ning prescribing to only abstinent 
users is recommended since their effectiveness during a period of current use would be expected to be poor both as a result of poor compliance and monoamine depletion. In addition there are at least theoretical causes for concern over potentially fatal interac-tions between MDMA and selective serotonin reuptake inhibitors (SSRIs) that have very rarely been reported, possibly because some SSRIs (i.e. citalopram) can inhibit the CYP2D6 enzyme.
(22) The 
precise effects of combining SSRIs and MDMA appears to be related

(22) The 
precise effects of combining SSRIs and MDMA appears to be related 
to whether use of the SSRI was before or after the MDMA and whether SSRI dosing is acute or chronic. For example, SSRIs given acutely after MDMA (taken by users to intensify the ecstasyeffects) may theoretically increase the risk of precipitating a sero-toninergic syndrome. It is probable that SSRIs and other classesof antidepressant can be used effectively in this group if a diagnosis of responsive affective/anxiety disorder is conﬁ  rmed and abstinence
is maint ained. CBT may be useful in this group both to address
their underlying drug as well as to address any coexisting anxiety/depressive disorders.
Dependence with the development of heavy regular use patterns 
is possible, though there are unlikely to be any speciﬁ  c signs or 
symptoms that differentiate diagnosis of management signiﬁ  cantly 
from other forms of stimulant dependence.
Methamphetamine-‘crystalline

Methamphetamine-‘crystalline 
methamphetamine hydrochloride’ ice, crystal, shabu, yaba, meth, tina
Methamphetamine is one of number of synthetic amphetamine 
type stimulants that includes dex-amphetamine. Whilst its use has been problematic in SE Asian countries such as Thailand, Japan, and Korea for many years it is only in the last decade that it has 
become a signiﬁ  cant problem in eastern Europe, America, Australia, 
and elsewhere. In the United Kingdom methamphetamine was 
reclassiﬁ  ed as Class A drug in 2007.
Preparation, purity, and routes of use
Unlike illicit amphetamine sulphate powder (speed), methamphet-

amine is often of very high purity. Crystalline methamphetamine hydrochloride (known as ice-because it can resemble shards of glass) can be up to 80% pure. Base amphetamine (sometimes known as paste), is an oily, waxy intermediate product on the way the manufacture of the crystalline hydrochloride salt of metham-phetamine and has a lower purity of about 40–50 per cent. Methamphetamine is a versatile drug and can be smoked, snorted, injected, and taken orally.
Mechanism of action and metabolism

Methamphetamine closely resembles amphetamine sulphate (commonly referred to as speed) in structure and mechanism of action but is considerably more potent in its sympathomimetic effects and has a longer duration of action (half-life about 12 h). Methamphetamine has both direct sympathomimetic effects sec-ondary to disruption of vesicular storage of monoamines and inhi-bition of their breakdown by MAOIs and indirect actions through inhibition of central presynaptic reuptake of catecholamines.Prevalence and patterns of use
In the United Kingdom reports of its use are becoming more common, particularly in association with the gay and dancemusic scene but compared to the use of cocaine in all its forms, the prevalence of methamphetamine use at present is still low.
(43)

(43)
Sympathetic arousal induced by methamphetamine produces rapid and sometimes irregular heartbeat, sweating, pupillary dilation, hypertension, dry mouth, tremor and blurred vision, and increased body heat. Occasionally, serious medical complications arise including coronary artery syndrome, seizures, and cerebral bleeds (see Table 4.2.3.5.2).
Psychological effects and complications
Acute sought after-effects are similar to those of amphetamine and include euphoria, enhanced stamina, conﬁ  dence, disinhibition, 
reduced appetite, improved coordination, and heightened alertness and awareness.
(a) Dependence and withdrawal

Dependence may occur and is more common among heavymale users and in those who smoke or inject the drug. Although dependent users may use every day to avoid withdrawal, more typically users tend to consume a large amount of the drug(often several grams) over several days going out without sleep(a binge) before ceasing use through physical exhaustion oran exhaustion of funds. ‘Crashing’ refers to the period followinga binge, which is characterized by fatigue, hypersomnia, hyper-phagia, and low mood due to acute monoamine depletion. The crash and subsequent comedown period may last 2–7 days.If abstinence persists a longer term withdrawal period may be seen, characterized by craving, low mood, anergia, irritability, sleep, and appetite disturbance. Similar neurobiological mecha-nisms involving alterations in the function and activity of the

monoamine neurotransmitters are responsible for the overlap 
between the symptoms of depression and those of stimulant withdrawal.
(42,44)  Typically the withdrawal gradually diminishes 
over 2–4 weeks though dysphoric symptoms may persist for up to 10 weeks.
(b) Withdrawal, depression, and management
The frequency of depressive symptoms is highest during the with-drawal period. As with alcohol, there are a far fewer number of people who present with depression symptoms outside of stimulant use or withdrawal. Management of withdrawal is largely supportive and with a safe, well-supported home environment.In patient admission is rarely required other than in those with severe mental or physical illness. The patient should be placed in quiet surroundings for several days and allowed to sleep and eat as much as is needed. Because a signiﬁ  cant component of the

withdrawal syndrome is probably related to neurotransmitter deple-tion, recovery may be delayed because of anorexia associated with amphetamine use. It may be useful in some to provide nutritional supplements or a well-balanced diet rich in monoamine precursors: phenylalanine, tyrosine, l-tryp tophan for example, pumpkin seeds, 
chocolate, marmite, bananas. Benzodiazepines may be prescribed 4.2.3.5 disorders relating to the use of ecstasy and other ‘party drugs’

SECTION 4  clinical syndromes of adult psychiatry 498
on a short-term basis for agitation. Some patients may become 
markedly despondent during withdrawal and a suicide assessment may be necessary.
Since antidepressants have no speciﬁ  c anti-craving effects, and 
the efﬁ  cacy of antidepressants in reducing depression is conﬁ  ned to 
those stimulant users who are depressed, it is useful to wait until after they have stopped using for 2–4 weeks and reassess them for depressive symptoms. The advantages of waiting are improved diagnostic accuracy, avoidance of potentially unnecessary medica-tion, and probably an improvement in compliance and efﬁ  cacy. 
However the persistence of depressive symptoms beyond 2–4 weeks after stopping amphetamine use may suggest that there is an underlying depressive illness and this should be treated
(42) since

(42) since 
left unmanaged its presence represents a high risk for relapse. Psychosocial treatments for stimulant abuse and dependence have been found to be effective in reducing levels of use,
(45) but to date, 
no reliably effective pharmacological treatments have been identi-ﬁ ed and there are currently no widely accepted evidence-based 
pharmacotherapy regimes for the treatment of psychostimulant withdrawal.
(46)
(c) Stimulant-induced psychosis

(46)
The use of high doses of methamphetamine may lead to the induction of a temporary psychotic state that may be clinically indistinguishable from paranoid schizophrenia. First recognized in 1938 in association with Benzedrine nasal inhalers, it was not until Connell’s classic 1958 study that the syndrome was well described. Acute transient psychotic episodes (typically characterized by suspiciousness, unusual thought content, or hallucinations) occur in about 10–15 per cent of users. Psychotic episodes are more com-mon in dependent users, men, injectors, and smokers, polydrug users, those with past history and following a binge in association with prolonged insomnia.
(47)
Characterized by persecutory delusions and hallucinations

(47)
Characterized by persecutory delusions and hallucinations 
which are typically auditory but may be visual or tactile (which can be associated with secondary delusion of parasitic infestation) amphetamine-induced psychosis typically remit within few days or at most a few weeks. Little has changed in the way of management since Connell’s time who recommends ‘removal of the drug and appropriate sedation’ . Often, patients present with high levels of hostility and violence secondary to persecutory delusions or hallu-cinations, and safe containment and management of the disturbed individual can require enormous levels of both physical and chem-ical restraint. Benzodiazepines (often required in very high doses) should be the ﬁ  rst-line medication with antipsychotics used only 
where additional tranquilization is required. A diagnosis of a pos-sible underlying or persistent psychotic disorder must be deferred 
until a reassessment can be made in a drug-free state. These often

until a reassessment can be made in a drug-free state. These often 
ﬂ orid psychoses usually remit within a few days and the user returns 
to normal functioning, although some retain a vulnerability to such episodes.
(48) Only a minority (1–15 per cent) persist beyond 1 
month and many of these patients will have underlying psychiatric disorders.
(47)
The prognosis is variable with those who have experienced 
stimulant-induced psychotic episodes being more vulnerable to future episodes (possibly through behavioural sensitization) on re-exposure to the drug often at lower levels. Recent positron emission tomography (PET) imaging studies in chronic metham-phetamine users have demonstrated a reduction in dopamine transporter concentration and this reduction was signiﬁ  cantly 
associated with the duration of methamphetamine use and closely related to the severity of persistent psychiatric symptoms. Moreover, the severity of psychiatric symptoms was signiﬁ  cantly correlated

with the duration of methamphetamine use. Cessation is still potentially important since there does however appear to be some recovery of dopamine transporter function with abstinence.
Gamma hydroxy butyrate, GHB, GBH, 
fantasy, G, liquid ecstasy, and GBL
GHB is an endogenous short-chain fatty acid found in the CNS 
and elsewhere in the body. A putative neurotransmitter, its precise role is yet to be identiﬁ  ed although speciﬁ  c binding sites have been 
identiﬁ  ed in hippocampus (linked to DA neurones). Trace amounts 
may also be found in certain fruits such a guava. In the United Kingdom GHB is classiﬁ  ed as Class C drug.
Like ketamine, GHB was originally developed as an anaesthetic 
though the high incidence of tonic clinic seizures dampened enthusiasm among surgeons for its routine use. Subsequently it found clinical utility as a sedative, a treatment for narcolepsy, as a detoxiﬁ  cation agent (it is effective in the management of alcohol

withdrawal) and as a putative muscle growth enhancer for body builders (through its effect on increasing slow wave sleep). Since the 1990s however it has become best known for its place among the smorgasbord of drugs commonly used by those involved in the dance/rave scene. It has a reputation as a cheap stimulant drug of short duration with marked aphrodisiac properties but a narrow therapeutic threshold carrying a signiﬁ  cant risk of overdose espe-
cially in combination with alcohol.
(49)
Preparation (pro drugs), purity, and routes of use
Until the late 1990s GHB and its precursors including the psychoactive pro compounds GBL (gamma butyl-lactone) and 1,4 butanediol were widely available over the Internet. Because of its relative ease of manufacture attempts at home production were common, resulting in preparations of widely varying con-centrations. The resultant formulations were sometimes caustic, resulting in gastrointestinal discomfort, vomiting, aspiration, and coma.

GHB is sold most commonly as a free acid (a colourless and 
odourless liquid in its pure form, with a slightly salty, acidic taste) or as a sodium salt (usually a white powder). Although varying widely in concentration typically doses are sold in plastic vials holding 5–10 ml.
GHB readily cross the BBB and acutely leads to a transient decrease followed by increase in dopamine levels (accompanied by increase in endogenous opioid release). Increases in other neurotransmitters such as GABA, Ach, and 5-HT are also seen. At higher doses it exhib-its some partial GABA-b activity (epileptogenic). GHB is usually taken orally often mixed in fruit juice or alcoholic beverage. It has a very rapid onset of action with noticeable effects occurring within 15 min of administration it has a relatively short duration of action(t
1/2 27 min) with effects peaking at 30–60 min and being over with-
in 2–4 h, being eliminated though its breakdown to CO2 and H2O.

499
GHB exhibits a very narrow therapeutic index and as a result 
of wide interpersonal variation in tolerance and significantly enhanced toxicity (depressant effects) when combined with alcohol, overdose with GHB has been reported more widely than for any other dance drug,
(50,51) overdose should be suspected in

(50,51) overdose should be suspected in 
someone who presents with nystagmus, ataxia, nausea, vomiting, sedation, weakness, bradycardia, hypotension, and the rapid onset of unconsciousness (quite similar to severe alcohol intoxication but without alcohol on the breath). Management should include placing the person in the recovery position, airway management and pulse oximetry. GCS scores may be very low (<7). If oxygen saturation drops or they are so unconscious that they can tolerate a Guedels airways then ventilation should be considered. Overdoses are short lived and most awake somewhat aroused and disorienta-tion after a few hours. Other clinical presentations include agitation, anxiety, coma, amnesia, and collapse. These patients when in coma may require ventilation and typically suddenly emerge from their coma with high levels of agitation, arousal, and 
violence.
Although there have been press reports of GHB being commonly

violence.
Although there have been press reports of GHB being commonly 
used as ‘date rape drug’ , such cases are very rare and it is still the case that the most common drug used for such purposes is alcohol alone.
Consumption of GHB results in a dose-related euphoria and stim-ulation which gives way to sedation at higher doses. In combina-tion with stimulant drugs there may be an increase of precipitating a brief psychotic reaction, whilst with alcohol the risk of fatal overdose is the primary concern. There has been a single case report of Wernicke Korsakoff syndrome.

More recently there have been number of reports describing GHB dependence and withdrawal. The later may present as a rapid onset, prolonged alcohol withdrawal picture. Although associated with lower levels of autonomic arousal and seizure risk, patients may exhibit marked confusion, delirium, and hallucinations. Management may require doses of diazepam markedly in excess of those typically used to manage alcohol withdrawal with a waxing and waning clinical progression that may last 2 weeks.
(52)
Ketamine (K, Special K, Super K, Vitamin K, 
Green, Mean Green, Jet)
Ketamine (2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone)

(52)
Ketamine (2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone) 
and PCP (angel dust) are very similar drugs, the main difference being ketamine’s shorter half and less problematic ‘emergence phenomena’ . Ketamine has a range of useful clinical applications. It is used across several areas of medicine including paediatric analgesia and anaesthesia, emergency anaesthesia, obstetrics, and battle-zones
(53) and beneﬁ  ts from having a wide margin of safety in 
overdose. Ketamine is an NMDA antagonist and is almost unique as an anaesthetic in its ability to produce a ‘dissociative’ state, which results in higher brain structures in the brain centres being

overdose. Ketamine is an NMDA antagonist and is almost unique as an anaesthetic in its ability to produce a ‘dissociative’ state, which results in higher brain structures in the brain centres being 
prevented from perceiving auditory, visual or painful stimuli leading to ‘a lack of responsive awareness’ . Overall the effect has been described as somato-aesthetic sensory blockade with amnesia and analgesia. In recent years its non-medical use as a psychedelic has become more common. In the United Kingdom ketamine is classiﬁ  ed as Class C drug. For a recent review see Wolff and 
Winstock.
(54)
Ketamine has multiple actions at numerous receptor sites particularly affecting glutaminergic and monoaminergic neuro-transmission. The most signiﬁ  cant pharmacological action of

Ketamine has multiple actions at numerous receptor sites particularly affecting glutaminergic and monoaminergic neuro-transmission. The most signiﬁ  cant pharmacological action of 
ketamine is the non-competitive antagonist binding at the cation channel of the NMDA receptor and consequent interference with excitatory amino acid transmitters—glutamate and aspartate. As a research probe in the study of schizophrenia, ketamine has given increasing prominence to the role of glutamate in the aetiology of psychotic illness. Ketamine also enhances monoaminergic trans-mission resulting in marked sympathomimetic effects as well as modulating activity at opioid receptors, thought to be responsible for its analgesic and dysphoric effects.
Ketamine undergoes marked ﬁ  rst-pass metabolism and is fairly

Ketamine undergoes marked ﬁ  rst-pass metabolism and is fairly 
ineffective when taken orally (bioavailability may be <20 per cent). However, oral consumption does result in a two-fold higher concentration of its primary metabolite norketamine compared to, for example, intramuscular dosing. Norketamine is pharmacologi-cally active with anaesthetic potency approaching one-third that of the parent compound. Hence although the onset of effects following ingestion may be somewhat slower than by parental routes the duration of effects would almost certainly be longer. The majority of the parent drug will be eliminated from the body within 24 h, although prolonged effects due to the presence of active metabolites may occur.
Ketamine may be sold illicitly in a number of preparations; as crystalline powder for intranasal use (dose-100–400 mg), in liquid, tablet, powder, or capsular form (dose-350–500 mg) for ingestion.

Ketamine may be sold illicitly in a number of preparations; as crystalline powder for intranasal use (dose-100–400 mg), in liquid, tablet, powder, or capsular form (dose-350–500 mg) for ingestion. 
When obtained from diverted licit sources, the formulation of the 
drug is a solution prepared for intravenous use. This solution may be injected or swallowed, but more typically the solution is dried and taken intranasally.
(54) However, this process of desiccation may 
reduce the purity of the crystalline residue, and is an obvious point at which, via contamination, purity may be altered. Ketamine may be adequately absorbed via the intranasal, intravenous, subcutane-ous, intramuscular, and intrathecal routes, with snorting and injecting being the most common recreational routes of use. Reports of clinical use via the rectal and transdermal routes have also been described.
Prevalence and patterns of use

Far less common in the general population than MDMA, ketamine none the less has become increasingly popular among those associ-ated with the dance scene with a prevalence of about 20 per cent being reported among clubbers. Whilst ketamine maintains a good safety record within clinical settings, the increase in its unregulated use outside such controlled environments is a cause for concern 4.2.3.5 disorders relating to the use of ecstasy and other ‘party drugs’

SECTION 4  clinical syndromes of adult psychiatry 500
with its effects being highly sensitive to age, dose, route, set, and 
setting (see Table 4.2.3.5.3). Outside clinical settings ketamine is most commonly snorted or injected, with typically administered doses being small fractions of a gram (an eighth). Because of its short half-life (17 min) the psychedelic effects experienced are gen-erally short-lived with effect duration of about 1–2 h. The short duration of effect and rapid onset of action when taken by intrana-sal or intravenous routes often leads recreational users to adminis-ter repeated doses over the course of an evening (session) in order to maintain a desired psychoactive effect.
Because of its fast urinary excretion (within 2 h) the ability to iden-tify ketamine in urine screens is almost impossible and thus a level of clinical suspicion is required especially if a history of its use is not forthcoming.

(55) Detection by clinical examination relies on 
identifying mydriasis, moderate tachycardia, elevated BP , slurred speech, blunted affect, ataxia, delirium, nystagmus (less commonly than with PCP). Tachycardia is the most common ﬁ  nding on phys-
ical examination. Its short half-life of 17 min (see Table 4.2.3.5.3).
Admissions to hospital are most commonly for complaints 
related to sympathetic over activity with chest pain, palpitations and taccycardia, nausea, vomiting, difﬁ  culty breathing, ataxia, 
temporary paralysis/inability to speak, blurred vision, no awareness of pain as well as derealization/depersonalization, and amnesia. Other risks associated with its use include accidents, trauma, and risky sexual behaviours. Rarely more severe complica-tions are reported including severe agitation and rhabdomyolysis. Although relatively safe in overdose, in combination with ethanol 
or other CNS depressants the use of ketamine can result in death.
Clinical ﬁ  ndings and detection

(a) Psychological effects and complications
At low doses marked elevation in mood predominate. At
higher doses intense psychedelic effects commence with sensory and perceptual distortion, euphoria, and out of body and ﬂ  oating 
experiences (see Table 4.2.3.5.3). The Harvard academic,Timothy Leary, described it as ‘the ultimate psychedelic journey’ . Users describe entering the ‘K hole’ where they experience—visits 
to god, aliens, their birth, past lives and the ‘experiences of evolu-tion’ . Some users report taking issues of set and setting into careful consideration prior to using ketamine such preparation cannot be performed if the drug is consumed unwittingly when it has been marketed under the guise of another drug such as ecstasy. Being an amnestic it may become difﬁ  cult to remember the total doses 
consumed.
Ketamine can also produce a psychotic picture that can brieﬂ  y

consumed.
Ketamine can also produce a psychotic picture that can brieﬂ  y 
mimic schizophrenia. Both positive and negative symptoms of schizophrenia can be transiently seen in normal users and its use can exacerbate symptoms in those with pre-existing psychotic dis-orders. Other adverse effects can include frightening hallucinations/out of body experiences, thought disorder, confusion, and dissocia-tion. Such episodes tend to be short-lived, resolving in a few hours or at the most a few days. In many respects these are similar to those adverse effects seen LSD, though with ketamine they come on after a shorter period following use and recede more quickly.
Management is by supportive monitoring (cardiovascular) in a

Management is by supportive monitoring (cardiovascular) in a 
quiet low stimulation room with symptomatic treatment with benzodiazepines if needed. Unusually, the effects of benzodiaze-pines are inconsistent varying between compounds and dose. For instance, whilst lorazepam may reduce emotional distress, it appears to have little impact upon the psychosis or perceptual changes observed. Midazolam, on the other hand, is able to negate 
ketamine’s effect on thought process and perceptual disorder but 
has little impact upon mood problems. Interestingly haloperidol also has little effect upon the psychosis associated with ketamine, suggesting a role for receptors other than D2. Chlorpromazine should be avoided (anticholinergic effects).
(a)  Ketamine dependence and long-term cognitive 
Animal studies demonstrate the ability for intravenous ketamine

Animal studies demonstrate the ability for intravenous ketamine 
to produce dependence in rat models, with disruption of operant behaviour on withdrawal. Ketamine demonstrates reinforcing efﬁ cacy in animal self-administration models and is found to be a 
discriminative stimuli in operant tasks. Its effects are thus readily distinguishable from other drugs and may have abuse liability. However, ketamine is somewhat unusual in its pharmacodynamics, almost acting as a partial antagonist with regard to brain reward enhancements, being stimulatory at low doses, and inhibiting brain reward centres at higher doses.
Clinically ketamine dependence has been described, with 
compulsive use as primary symptom. Heavy habitual use has been described by Jansen (1990), and cases of dependence have also been reported among anaesthetic staff. Although tolerance

compulsive use as primary symptom. Heavy habitual use has been described by Jansen (1990), and cases of dependence have also been reported among anaesthetic staff. Although tolerance 
develops there are only a few case reports of a withdrawal syndrome 
occurring.
Longer-term follow-up studies suggest that any impairment of 
semantic memory may be reversible upon cessation of use but per-sistent deﬁ  cits may be seen in episodic memory and in subjective 
experience with one study suggesting persistence of schizotypal and perceptual changes after cessation of use.
(56)
(b)  New class of drugs
Tryptamine (1H-indole-3-ethanamine) is a naturally occurring metabolite of tryptophan. It forms the parent nucleus of a wide Table 4.2.3.5.3  Ketamine, psychological and physical effects
Psychological Physical
Rapid onset, short duration of action (1 h), 
 wide safety margin
Dissociative anaesthesia ‘somatosensory 
 blockade’ analgesiaDilated pupils

Perceptual distortion/hallucinations/near death Tachycardia
Out of body experience HypertensionThough disorder/synaethesia AtaxiaEmergence phenomena ParalysisCognitive impairment SweatingAmnesia HypersalivationDerealization/depersonalization Little effect on cough reﬂ  ex

501
range of hallucinogenic drugs, some entirely synthetic (LSD, N,N-
dimethyltryptamine) but many naturally occurring in plants, fungi (psilocybin—the psychoactive component of ‘magic mush-rooms’), and occasionally animals. It seems unlikely that many tryptamines other than LSD and psilocybin will be used undulyin dance clubs because they possess few stimulant properties,and need to be smoked or injected because most are inactiveby mouth unless taken with a monoamine oxidase inhibitor.An example of the latter is the combination of N,N-dimethyltrypt amine 
(the hallucinogen) and harmine (the activator) in the hallucino-genic drink ayahuasca or caapi used in rituals by South American Indians. Drugs such a N,N-dimethyltryptamine may have
adverse effects upon both the cardiovascular system and ontemperature regulation. They may induce unpleasant hallucino-genic experiences.
As described earlier the analogues MBDB, MDEA, and MDA

As described earlier the analogues MBDB, MDEA, and MDA 
all share similar properties with MDMA and at times have been marketed as distinct drugs. More recently 4-Bromo-2, 5-dimethoxy-phenethylamine (also known as 2C-B, Nexus) a drug with similar hallucinogenic properties as psilocybin and mescaline has become available within the dance scene in Europe. Others such a 2C-T2 (2,5-dimethoxy-4-ethylthio- β-phenethylamine) suggest that new 
additions to an expanding street pharmacy are unlikely to become 
a thing of the past any time soon. Newer drugs are likely to be less easily detected by toxicologist and may have unfamiliar or atypical clinical manifestations.

MDMA, methamphetamine, GHB, and ketamine are all capable of producing acute adverse psychological experiences in normal users and exacerbating symptoms in those with underlying psychological disorders. They also to varying degrees pose therisk of long-term neuropsychiatric consequences. Although dependent patterns of use are not commonly seen with thisgroup of drugs, me thamphetamines certainly can result in the very 
rapid development of severe dependence. M ost acute presenta-
tions are typical ly short-live d and self-limiting and are only very

tions are typical ly short-live d and self-limiting and are only very 
rarely life-threatening. The precipitation of an underlying psychi-atric disorder or an exacerbation of premorbid traits may well be one of the longer term consequences of heavy use of these drugs. In those who present with acute drug-related psychological symp-toms there should be an emphasis on follow-up since in some cases the symptoms will represent the onset of a persistent inde-
pendent disorder which requires treatment. Users who have expe-
rienced acute psychological problems should be encouraged to make the attribution that there may be something inherent in them that makes them susceptible to experiencing the unpleasant reactions with a drug and that they are likely to remain vulnerable to those adverse experiences. This may be difﬁ  cult to accept for

potentially vulnerable young people who may prefer to think that the experience was not enjoyable because the drugs were not good – ‘it was a bad pill’ .
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4.2.3.6 Disorders relating to the 
use of volatile substances

Volatile substance abuse ( VSA )—also known as ‘solvent abuse’ 
and ‘inhalant abuse’—is the deliberate inhalation of any of a range of products (see Table 4.2.3.6.1
(1)), to achieve intoxication. Amyl 
(pentyl) and isobutyl nitrites (‘poppers’) have different patterns of misuse, and are not discussed here.
(2)
VSA has dose-related effects similar to those of other hypnoseda-
tives. Small doses rapidly lead to ‘drunken’ behaviour similar to the

503
effects of alcohol, and may induce delusions and hallucinations. 
Some heavy misusers inhale large quantities; 6 l of adhesive weekly have been reported.
Long-term effects include listlessness, anorexia, and moodiness. 
The hair, breath, and clothing may smell of the substance(s) used, and empty product containers (e.g. glue cans, cigarette lighter 
reﬁ lls, and aerosol spray cans), and bags used to inhale from, may 
be found.
Being readily available, volatile substances are, along with 
alcohol and tobacco, the ﬁ  rst intoxicating substances some children 
try. However, most VSA is experimental and does not lead to the use of other psychoactive substances; problematic misusers have other difﬁ  culties in their lives.
(3)
History
Inhaling substances to achieve intoxication is not new. Inhaling 
ether and nitrous oxide (‘laughing gas’), as well as commercially available volatile products, has a long history.
Public concern is more recent. In the United States during

Public concern is more recent. In the United States during 
the 1950s and 1960s there was much publicity about glue snifﬁ  ng; 
this helped to publicize the possibilities of glue as an intoxicant.
(4)
Only in the 1970s did public concern about VSA emerge in the United Kingdom, to reach a peak in 1983 when there were more press cuttings on the subject than on all other drugs.
(5) Public anxiety 
has since waned, although the problem has not disappeared.
Prevalence of VSA
VSA is a worldwide problem. For an overview, see a WHO report,(6)
and a National Institute on Drug Abuse (NIDA) report.(7) The 
European Schools survey Project on Alcohol and other Drugs (ESPAD) report provides 2003 data from 35 European countries: lifetime experience of VSA (i.e. whether ever tried VSA) among

European Schools survey Project on Alcohol and other Drugs (ESPAD) report provides 2003 data from 35 European countries: lifetime experience of VSA (i.e. whether ever tried VSA) among 
15- to 16-year-olds varied from 2 per cent (in Romania) to 22 per cent (in Greenland). In the United Kingdom (and Iceland) 12 per cent reported trying VSA—nine countries had a higher prevalence. There was little difference between boys’ and girls’ lifetime prevalence.
(8) Although young people from all socio-economic 
groups experiment with volatile substances, for some among the poor and the dispossessed, VSA is the drug of choice.
(9) VSA is a 
particular problem among people living on the street. Chronic VSA is associated with poor socio-economic conditions, with delin-quency and illegal drug use,
(10) disrupted families, and other social 
and psychological problems.(11)
VSA deaths
Even for ﬁ  rst-time experimenters, death from VSA is an ever-

VSA deaths
present risk. Death may ensue from convulsions and coma, inhala-tion of vomit, or direct cardiac or central nervous system toxicity. Sudden deaths of young people should be thoroughly investigated, as VSA-related deaths can be overlooked. Post-mortem examina-tion usually reveals little, except perhaps acute lung congestion and possibly cold-induced burns to the mouth and throat. T oxicological examination of blood and tissue specimens is used to conﬁ  rm a 
diagnosis of VSA-related death.
(12)
A long-term study in the United Kingdom identified 2152 
VSA-related deaths between 1971 and 2004.(13) The death rate

(12)
VSA-related deaths between 1971 and 2004.(13) The death rate 
peaked in 1990 with 152 deaths, declining since, with 47 deaths being recorded in 2004. Under-18s make up half the deaths, although the age of death is increasing. Most are male, although the overall proportion of female deaths has risen and in the ﬁ  rst 5 years 
of the new millennium females comprised 22 per cent of the deaths (Table 4.2.3.6.2). Volatile-substance-related deaths occur in all social classes in the United Kingdom. However, ‘ . . . in deaths of Table 4.2.3.6.1  Some products which can be abused by inhalation
Product Major volatile components
Adhesives
Balsa wood cement Ethyl acetateContact adhesives Butanone, hexane, toluene, and estersCycle tyre repair cement Toluene, and xylenes
Woodworking adhesives Xylenes
Polyvinylchloride (PVC) 
cementAcetone, butanone, cyclohexanone, 
trichloroethylene
Aerosols

Aerosols
Air freshener LPG, DME, and/or ﬂ  uorocarbons
Deodorants, antiperspirants LPG, DME, and/or ﬂ  uorocarbons
Fly spray LPG, DME, and/or ﬂ  uorocarbonsHair lacquer LPG, DME, and/or ﬂ  uorocarbonsPaint sprayers LPG, DME, and/or ﬂ  uorocarbons and esters
Anaesthetics/analgesics
Inhalational Nitrous oxide, cyclopropane Diethyl ether, 
halothane, enﬂ  urane, isoﬂ  urane
Topical FC 11, FC 12, monochloroethane
Dust removers (air brushes)
DME, FC 22
Commercial dry cleaning and 
degreasing agents
Dichloromethane, FC 113, methanol, 1,1,1-tri- chloroethane, tetrachloroethylene, toluene,trichloroethylene (now rarely carbontetrachloride, 1,2-dichloropropane)
Domestic spot removers and 
dry cleaners
Dichloromethane, 1,1,1-Trichloroethane, tetrachloroethylene, trichloroethylene
Fire extinguishers
Bromochlorodiﬂ  uoromethane, FC 11, FC 12
Fuel gases

Fuel gases
Cigarette lighter reﬁ  lls LPG‘Butane’ LPG‘Propane’ Propane and butanes
Nail varnish/nail varnish 
remover
Acetone and esters
Paints/paint thinners
Acetone, butanone, esters, hexane, toluene, 
trichloroethylene, xylenes
Paint stripper
Dichloromethane, methanol, toluene
‘Room odorizer’
(Reproduced from B. Flanagan and R. Ives Volatile substance abuse, Bulletin on Narcotics , 
XLVI , 49–78, copyright 1994, UNODC.).4.2.3.6 disorders relating to the use of volatile substances

SECTION 4  clinical syndromes of adult psychiatry 504
those under 16, there was a marked difference in mortality between 
social classes I and V , with nearly four times as many deaths occur-ring in social class V . . . compared with social class I’ .
(14)
Health issues
Health effects of volatile substances include the following:
X A sensitization of the heart—so that cardiac arrhythmias may 
occur if VSA is followed by exertion or fright.
X Cooling of the throat tissues—caused by spraying substances 
directly into the mouth, which may causing swelling and suffocation.
X A risk of ﬁ  re—especially when combined with smoking; many 
products are inﬂ  ammable.
X Suffocation—a particular danger if large plastic bags are used.
X Most products are mixtures of chemicals, and manufacturers 
do not list the constituents. Changing product formulations make the dangers unpredictable.
X Using alone in an isolated place presents special hazards.

X When combined with alcohol or other drugs, the effects can be 
unpredictable.
X Intoxication itself has potential dangers, for example, greater 
recklessness, doing bizarre things in response to hallucinations, becoming unconscious, and choking on vomit.
Apart from the real risk of death, VSA rarely causes long-term 
damage. However, some products contain poisonous substances, such as lead in some petrol or n-hexane in some glues. Chronic

damage. However, some products contain poisonous substances, such as lead in some petrol or n-hexane in some glues. Chronic 
abuse of toluene-containing products and of chlorinated solvents such as 1,1,1-trichloroethane sometimes causes damage to the liver and kidneys. Damage to the lungs, bone marrow, and nervous system is also known, but is uncommon and generally reversible. Some people are more vulnerable (genetically or otherwise) than others to certain harmful effects. However, the long-term effects of snifﬁ  ng have not been thoroughly studied, and virtually all reports 
of chronic toxicity are case studies, so the actual morbidity from VSA is not known.
A review article looking at the possibility of cognitive impair-
ments concluded that: ‘the possibility that permanent structural brain damage, with accompanying psychiatric manifestations, results from solvent abuse remains inconclusive’ .
(15)

(15)
Users develop tolerance. Although no dependence syndrome 
exists, a few young people develop a more compulsive and long-term habit. The UK Advisory Council on the Misuse of Drugs suggested that: ‘There are . . . pharmacological reasons for suspect-ing that persistent exposure to volatile substances might be able to induce a dependence of the so-called depressant type’ .
(16)
Many volatile substance misusers are also users of other drugs, 
both legal and illegal. Poly-drug use may potentiate the effects of individual drugs and make it difﬁ  cult to assess the risks of individ-
ual substances.(17)
VSA during pregnancy is associated with increased maternal 
and foetal morbidity.(18) Paternal exposure to volatile substances 
may also have deleterious effects on their offspring.(19) But the

may also have deleterious effects on their offspring.(19) But the 
complexities of the chemicals involved—and the complexities of people’s lives—make it difﬁ  cult to identify speciﬁ  c causes of foetal 
damage difﬁ  cult.
Treatment of VSA-related disorders
Emergency treatment
The immediate treatment of an intoxicated person needs a calm 
and ﬁ  rm approach. The product being misused should be removed; 
although not if this would lead to conﬂ  ict—exertion or high emo-

tion may raise adrenaline to dangerous levels for an over-sensitized heart. Therefore, an intoxicated person should be kept calm and never chased. It is unlikely that it will be possible to have a serious conversation with an intoxicated misuser, but calming and reassur-ing talk may help. After 5 to 20 min without inhalation the abuser will sober up (unless alcohol or other drugs have also been used). Subsequently, medical help might be needed; a check-up may identify particular health problems.
Cessation

Cessation
No special regime is necessary when stopping misusing volatile substances. Although, being lipid-soluble, the chemicals may be detectable in the body tissues for some weeks after cessation of use, they do not have any psychoactive effect. There is no clearly deﬁ ned withdrawal syndrome and special detoxiﬁ  cation regimes 
are unnecessary, but rest, sleep, and good food may aid recovery.
Dealing with experimental misuse
Most teenagers never even try misusing volatile substances; those who do, do so only a few times, and even those who do so more frequently do not continue for long. Experimental or the occasional misuse of volatile substances occurs mainly from curiosity or as part of peer group activity. Appropriate intervention may simply involve a warning of the dangers, plus increased supervision. Specialist treatment is not required, and may be counterproductive, entrenching an otherwise transient activity.
Dealing with dependent misuse

Biology may predispose to dependent use, but chronic VSA is connected with other problems. As group of United Kingdom professionals put it:
(20)
Persistent misuse of volatile substances is a complex behaviour . . . frequently associated with low self-esteem, family problems, isolation and psychological difﬁ  culties. These are factors that may also be asso-
ciated with the problematic use of legal and illegal drugs, and indeed, Table 4.2.3.6.2  VSA-related deaths in the United Kingdom—selected years
Year 1983 1985 1987 1989 1990 1993 1996 1998 1999 2000 2001 2002 2003 2004
N 82 117 115 113 152 79 78 80 75 66 63 65 53 47
Reproduced from Field-Smith, M.E., Butland, B.K., Rarnsey, J.D.  and Anderson, H.R. Trends in deaths associated with abuse of vo latile substances 1971–2004, copyright 2006, St. George’s 
University of London, London.

505
a large proportion of people who misuse volatile substances also 
misuse other drugs. Chronic VSA is thus intertwined with social and psychological problems and with the misuse of illegal drugs. Therefore, counselling services for young people should not be narrowly focused on volatile substances, but should be able to deal with VSA in the context of a range of problematic behaviours.
Often, these other problems need attention ﬁ  rst, and until these

Often, these other problems need attention ﬁ  rst, and until these 
are dealt with, the misuser—even while recognizing the harm—may not give up. Consequently, generic services, which can deal more effectively with these broader problems, should lead on care, supported where necessary by specialist agencies. Mental health services, as well as drugs’ services, have an important role in giving this support, for example, in the treatment of psychiatric comor-bidity (dual diagnosis). Specialist services can also help to identify areas for intervention; implementation should take account of social and cultural patterns of the misuser’s life. Female volatile substance misusers may not readily present for treatment and can suffer additional stigmatization. Services for young people need to be specifically designed for their needs and cognizant of issues such as conﬁ  dentiality and consent. Families who struggle 
unaided with problematic VSA by a young family member may 
also need help.

The Modiﬁ  ed Social Stress Model, developed by the WHO Street 
Children Project, gives a framework for understanding substance use.
(21) Potential for change can be assessed using Prochaska 
and DiClemente’s ‘revolving door’ model of stages of change.(22)
Jumper-Thurman and colleagues point out that the treatment of volatile substance misusers:
(23)
has presented a particularly difﬁ  cult challenge . . . given the general 
lack of direction for effective treatment strategies. In addition to the physiological, neurological, and emotional challenges abusers face . . . [they] bring with them a multitude of other problems—academic, legal, social, and family issues.
Some groups (such as people living on the street, and indigenous

Some groups (such as people living on the street, and indigenous 
peoples) have special problems with substance use that require dif-ferent, more holistic, attention. Treatment should work ‘with the grain’ of the culture, rather than imposing inappropriate ‘alien’ treatment models. Indigenous peoples are beginning to insist that their cultures have useful perspectives and approaches that can be utilized in the treatment of people with drug and volatile substance problems.
(24)
Follow-up
After-care, long-term rehabilitation, social reinsertion, relapse management, and follow-up of discharged patients are important aspects of the treatment process.
Relapse, which is common, should be treated non-judgementally; 
not as ‘failure’ but as an opportunity for learning. Support in main-taining improvements may be helpful; for example, events for ex-users of volatile substances to help them to maintain abstinence and to utilize group support.
Harm minimization

Because of the unpredictable dangers of VSA, harm minimization advice should not be routinely given. However, very entrenched misusers may beneﬁ  t from careful individual guidance on mini-
mizing the risks, such as avoiding spraying gases directly into the mouth.Wider aspects
Chronic VSA is not an individual problem: it arises not only from individual pathology, but also from failures in social structures. Treatment, in the broadest sense, needs to help the healing of the family, the community, and to assist in making changes in society.
Measuring outcomes
Evaluation and monitoring need careful thought and planning. But treatment interventions have multiple aims and varied outcomes. Aims may alter and be adapted as the work develops, so that out-comes will be difﬁ  cult to assess in relation to the original aims.

Evaluation should handle this complexity: identifying ‘success’ requires measures beyond the simple calculation of reduction in, or abstention from, substance use.
Building evaluation in from the start, and using it to inform the 
intervention throughout, makes it part of the process of interven-tion; the reﬂ  ection that monitoring and evaluation encourages can 
increase the effectiveness of the intervention.
There are many different sniffable products, many possibilitiesfor substitution of one product for another, many differentchemicals involved, and insufﬁ  cient information about the relative 
harm of various products and practices. Volatile substancemisusers are generally young, and VSA-related deaths aresudden and unpredictable. All these factors make preventiondifﬁ cult.
Tackling the supply of products
This can be approached in several ways:
X Product elimination—while it is not possible to eliminate all

X Product elimination—while it is not possible to eliminate all 
volatile substances, some products are particularly dangerous, and have satisfactory substitutes.
X Product modiﬁ  cation—there are three possibilities (a review 
paper gives more details:(25))
• changing the formulation of the product to remove the 
intoxicating substance. There has been great success in Australian indigenous communities through substituting petrol with unsniffable ‘Opal’ , an unleaded fuel with low levels of aromatics
(26,27)
• adding a chemical to make the product unpalatable
(experiments with the bittering agent, Bitrex , have been
inconclusive)
• and modifying the container to make misuse difﬁ  cult.
X Warning labels—these may be helpful, although labelling draws 
attention to the potential for misuse. Many sniffable products in the United Kingdom carry the ‘SACKI’ warning, ‘Solvent Abuse Can Kill Instantly’ .
(28)

(28)
X Education for suppliers—retailers need information and
advice about a product’s potential for misuse. This is difﬁ  cult,
as the various products are sold through many retail outlets.
X Legal controls on the sale and supply of misusable products—
these exist in many countries but are difﬁ  cult to enforce.4.2.3.6 disorders relating to the use of volatile substances

SECTION 4  clinical syndromes of adult psychiatry 506
Tackling the demand for products
X Legal controls—in Japan, Singapore, and the Republic of Korea, 
VSA is an offence. However, this is not so in most countries because the criminalization of misusers of volatile substances is considered counterproductive.
X Information and education—this can be provided through
public advertising, leaﬂ  ets, helplines, in schools and informal 
education. Early education about volatile substances is essential; these products are in most people’s homes and therefore (unlike illegal drugs) they can be accessed by very young children. Because many parents are unaware of the misuse potential of household products, information should also be targeted atparents.
All these strategies should be considered; as the Advisory Council 
on the Misuse of Drugs pointed out, ‘good practice’ will constitute a layered series of alternative or multiple strategies rather than any one master stroke.
(29)

(29)
Advisory Council on the Misuse of Drugs. (1995). Volatile substance abuse .
HMSO, London.
Skellington Orr, K. and Shewan, D. (2006). Review of evidence relating to 
volatile substance abuse in Scotland . Scottish Executive
Substance Misuse Research Programme, Edinburgh(www.scotland.gov.uk/Resource/Doc/147377/0038818.pdf accessed 22-03-07).
The UK Government’s. (2005). Strategy for tackling volatile substance ( Out
of sight—Not out of mind. Children, young people and volatile substance 
abuse  (VSA )A framework for VSA ) can be downloaded from http://
www.dh.gov.uk/assetRoot/04/11/56/05/04115605.pdf.) (accessed 22-03-07).
Flanagan, R.J., Streete, P .J., and Ramsey, J.D. (1997). Volatile substance

Flanagan, R.J., Streete, P .J., and Ramsey, J.D. (1997). Volatile substance 
abuse: practical guidelines for the analytical investigation of suspected cases and interpretation of results . United Nations Drug Control 
Programme, Vienna.
Field-Smith, M.E., Butland, B.K., Ramsey, J.D., et al. (2006). Trends in deaths 
associated with abuse of volatile substances 1971–2004 . St George’s, 
Ron, M. (1986). Volatile substance abuse: a review of possible long-term 
neurological, intellectual and psychiatric sequelae. The British Journal 
of Psychiatry ,148, 235–46.
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Inhalants%20and%20solvents.pdf (accessed 22-03-07).
Information on UK VSA-related deaths: www.vsareport.org
USA National Inhalants Prevention Coalition: www.inhalants.org
1. Flanagan, B. and Ives, R. (1994). Volatile substance abuse. Bulletin on

1. Flanagan, B. and Ives, R. (1994). Volatile substance abuse. Bulletin on 
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2. Haverkos, H. and Dougherty, J. (eds.) (1988). Health hazards of nitrite 
inhalants, NIDA Research Monograph 83 . National Institute on Drug 
Abuse, Rockville, MD.
3. Davies, B., Thorley, A., and O’Connor, D. (1985). Progression of 
addiction careers in young adult solvent misusers. British Medical 
Journal ,290, 6482.
4. Brecher, E. (1972). How to launch a nation-wide drug menace. In 
Licit and illicit drugs , (eds. E.M. Brecher and the Editors of Consumer 
Report Magazine) pp. 321–34. Little, Brown, Boston, MA.
5. Ives, R. (1986). The rise and fall of the solvents panic. Druglink ,
1, 10–12. 6. WHO Programme on Substance Abuse. (1999). Volatile substance 
abuse: a global overview . WHO, Geneva.
 7. Kozel, N., Sloboda, Z., and De La Rosa, M. (eds.) (1995). Epidemiology

 7. Kozel, N., Sloboda, Z., and De La Rosa, M. (eds.) (1995). Epidemiology 
of inhalant abuse: an international perspective (NIDA Research 
Monograph series No. 148) . NIDA, Washington, DC.
 8. Ives, R. (2006). Volatile Substance Abuse: a review of ﬁ  ndings in ESPAD 
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 9. Beauvais, F., Wayman, J. C., Jumper-Thurman, P ., et al. (2004). Inhalant 
abuse among American Indian, Mexican American, and non-Latino 
white adolescents. The American Journal of Drug and Alcohol Abuse ,
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young adolescents  (USA ‘National Survey on Drug User and Health’) 
(http://oas.samhsa.gov/2k5/inhale/inhale.htm (accessed 22-03-2007)).
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Health Education Authority, London.

12. Flanagan, R.J., Streete, P .J., and Ramsey, J.D. (1997). Volatile substance 
abuse: practical guidelines for the analytical investigation of suspected cases and interpretation of results. United Nations Drug Control 
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deaths associated with abuse of volatile substances 1971–2004 .
St George’s, University of London, London.
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substance abuse in those under 18 years: results from a national 
epidemiological study. Archives of Disease in Childhood ,69, 356–60 
(see p. 358).
15. Ron, M. (1986). Volatile substance abuse: a review of possible

15. Ron, M. (1986). Volatile substance abuse: a review of possible 
long-term neurological, intellectual and psychiatric sequelae. The British Journal of Psychiatry ,148, 235–46.
16. Advisory Council on the Misuse of Drugs. (1995). Volatile substance 
abuse , paragraph 3.11. HMSO, London.
17. Ives, R. and Ghelani, P . (2006). Polydrug use (the use of drugs in 
combination): a brief review. Drugs: Education, Prevention and Policy ,
13, 225–32.
18. Wilkin, H. and Gabow, P . (1991). T oluene abuse during pregnancy: 
obstetric complications and perinatal outcomes. Obstetrics and 
Gynaecology ,77, 504–8.
19. Robaire, B. and Hales, B. (1993). Paternal exposure to chemicals before 
conception (editorial). British Medical Journal ,307, 341–2.
20. Network VSA. (1997). Network VSA statement about volatile substance 
misuse . Network VSA, Blackburn, Lancs.

21. WHO Programme on Substance Abuse. (1997). Street children, 
substance use and health: training for street educators , p. 48. 
22. Prochaska, J. and DiClemente, C. (1986). T owards a comprehensive 
model of change. In Treating addictive behaviours: processes of change
(eds. W. Miller and N. Heather), pp. 3–27. Plenum Press, New Y ork.
23. Jumper-Thurman, P ., Plested, B., and Beauvais, F. (1992). Treatment 
strategies for volatile substance abusers in the United States. In Inhalant 
abuse: a volatile research agenda  (eds. C. Sharpe, F. Beauvais, and 
R. Spence), NIDA Research Monograph 129. National Institute on Drug Abuse, Rockville, MD.
24. Brady, M. (1992). Heavy metal. The social meaning of petrol snifﬁ  ng in 
Australia . Aboriginal Studies Press, Canberra.

25. MacLean, S. and d’Abbs, P . (2006). Will modifying inhalants reduce 
volatile substance misuse? A review. Drugs: Education, Prevention and 
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scheme . Australian Government Department of Health and Human 
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abuse , paragraph 5.5. HMSO, London.

507
4.2.3.7 The mental health 
effects of cannabis use
Wayne Hall
Cannabis the drug
Cannabis products are derived from the female plant of 
Cannabis sativa  and contain the psychoactive constituent delta-9-
tetrahydrocannabinol ( THC ).(1) Marijuana (THC content typically 
0.5–5 per cent) is prepared from the dried ﬂ  owering tops and 
leaves of the plant. Hashish (THC content typically 2–20 per cent) consists of dried cannabis resin and compressed ﬂ  owers.
(1)
Cannabis is usually smoked in a ‘joint’ , like a tobacco cigarette, or 
in a water pipe, often mixed with tobacco. Although marijuana and hashish may be eaten, cannabis is usually smoked because this is the most efﬁ  cient way to achieve the desired effects.
(2)
THC acts on a widely distributed, speciﬁ  c receptor in brain 
regions that are involved in cognition, memory, reward, pain perception, and motor coordination.
(1) These receptors respond

(2)
(1) These receptors respond 
to an endogenous ligand, anandamide, which is considerably less potent and has a shorter duration of action than THC.
(1)
Patterns of cannabis use
Cannabis has been tried by many young adults in Europe, the United States, and Australia.
(3) Most cannabis users in these coun-
tries start in their mid to late teens and stop in their middle to late 20s.
(3,4) In the United States and Australia, about 10 per cent of 
those who ever use cannabis become daily users, and another 20 to 30 per cent use weekly.
(3) This pattern of use differs from that 
found in traditional cannabis-using countries, such as Egypt and India, where recreational cannabis use is uncommon and heavy cannabis use is conﬁ  ned to small, marginalized groups.
(3)

(3)
‘Heavy’ cannabis use is usually deﬁ  ned as daily or  near-dail y use.(5)
This pattern of use places users at the greatest risk of experiencing 
adverse psychological and physical consequences.(2,3) Daily cannabis 
users are also more likely to be regular users of alcohol and tobacco and to use amphetamines, hallucinogens, psychostimulants, sedatives, and opioids.
(2,3)
Acute psychological effects of cannabis use
Cannabis produces euphoria and relaxation, perceptual alterations, impaired short-term memory and attention, and intensiﬁ  cation of 
ordinary sensory experiences.
(2) The most common unpleasant 
psychological effects are anxiety and panic reactions,(2) that are 
most often reported by naive users and are a common reason for discontinuing use.
(2) Cannabis produces dose-related impairments

(2) Cannabis produces dose-related impairments 
in cognitive and behavioural functions that may impair ability to drive an automobile.
(6)
Chronic psychological effects of 
cannabis use
Cannabis dependence
Animals and humans develop tolerance to the effects of THC,(1)
and some heavy users experience withdrawal symptoms on the abrupt cessation of cannabis use.(7) During the 1990s there was an 
increase in the number of persons in the United States, Australia, and Europe seeking help to stop their cannabis use.
(3)
A cannabis-dependence syndrome occurs in heavy chronic users 
of cannabis who report problems in controlling their cannabis use, 
but who continue despite experiencing adverse personal and social consequences.
(8) The lifetime prevalence of cannabis abuse and 
dependence (as deﬁ  ned in DSM-IIIR) in the United States has been

dependence (as deﬁ  ned in DSM-IIIR) in the United States has been 
estimated at 4.4 per cent of adults.(9) Around 10 per cent of those 
who ever use cannabis will meet criteria for dependence at some point in their lives.
(2,9)
It is not clear how cannabis dependence is best managed. Roffman 
and Stephens,(10) in summarizing the results of controlled trials of 
cognitive behavioural, relapse prevention and other psychological approaches to treatment, report low rates of absti-nence at 12 months but substantial reductions in cannabis use and problems among those who continue to use cannabis.
Cannabis psychosis
High doses of THC have been reported to produce visual and auditory hallucinations, delusional ideas, and thought disorder in normal volunteers.
(2) In traditional cannabis-using cultures, such

(2) In traditional cannabis-using cultures, such 
as India, a ‘cannabis psychosis’ has been reported in which the symptoms are preceded by heavy cannabis use and remit after abstinence
(11) but the existence of a ‘cannabis psychosis’ in Western 
cultures is still a matter for debate.(11)
Cannabis and schizophrenia
Cannabis use and schizophrenia are associated(12,13) and there 
is consistent evidence from a series of prospective studies in a number of different countries suggesting that cannabis use can precipitate schizophrenia in persons who are vulnerable because of a personal or family history of this disorder,
(12,13) and possibly a 
genetic vulnerability.(14) This hypothesis is consistent with the 
stress-diathesis model of schizophrenia(15) and it is also biologi-

cally plausible because psychotic disorders involve disturbances in the dopamine neurotransmitter systems and cannabinoids, such as THC, increase dopamine release.
(1)
Individuals with psychotic symptoms who use cannabis should 
be encouraged to stop or, at the very least, to reduce their frequency of use. The major challenge is in ﬁ  nding ways to persuade individ-
uals with psychoses to stop doing something they enjoy and to help those who want to stop using cannabis but ﬁ  nd it difﬁ  cult to do so. 
Psychological interventions for cannabis dependence in individuals without psychoses produce modest rates of abstinence and many individuals with schizophrenia lack social support, may be cogni-tively impaired, are often unemployed, and may not comply with treatment. A recent Cochrane review
(16) found no clear evidence

(16) found no clear evidence 
that supported any type of substance abuse treatment in schizo-phrenia over standard care. The development of more effective pharmacologic and psychological methods of treatment for canna-bis dependence in persons with psychoses is a research priority.
Other disorders
Cannabis use acutely impairs cognitive functioning but long-term heavy use of cannabis does not appear to produce severe or grossly 4.2.3.7 the mental health effects of cannabis use

SECTION 4  clinical syndromes of adult psychiatry 508
debilitating impairment of cognitive function that is comparable to 
the impairments found in chronic heavy alcohol drinkers.(17) There 
is evidence that the long-term use of cannabis produces more sub-tle cognitive impairment in the higher cognitive functions of mem-ory, attention and organization, and the integration of complex information.
(16) This evidence suggests that, longer the period of 
heavy cannabis use, the more pronounced is the cognitive impair-ment.
(17) But it remains to be decided whether these cognitive 
impairments antedate cannabis use, reﬂ  ect poorer learning in non-
academically oriented young people, or reﬂ  ect neurotoxic effects of 
cannabis use that can be reversed after an extended period of abstinence.
(18)
An ‘amotivational syndrome’

(18)
Anecdotal reports that chronic heavy cannabis use impairs motiva-tion and social performance have been described in societies with a long history of cannabis use, such as Egypt, the Caribbean, and elsewhere.
(2) A similar pattern of behaviour among young 
Americans who were heavy cannabis users in the early 1970s was described as an ‘amotivational syndrome’ .
(19) Field studies of 
chronic heavy cannabis users in societies with a tradition of such use, for example Costa Rica and Jamaica,
(2) have produced

(2) have produced 
evidence that has usually been interpreted as failing to demonstrate the existence of the amotivational syndrome. Critics have argued that these studies are unconvincing because the chronic users stud-ied have come from socially marginal groups, so that the cognitive and motivational demands of their everyday lives were insufﬁ  cient 
to detect any impairment caused by chronic cannabis use.
(2)
The status of the amotivational syndrome remains contentious. 
Many clinicians find the cases of ‘amotivational syndrome’ compelling, while many researchers are more impressed by the largely negative ﬁ  ndings of the ﬁ  eld and epidemiological studies. 
Regular cannabis users can experience a loss of ambition and impaired school and occupational performance
(2) and former

(2) and former 
cannabis users report that impaired occupational performance was their reason for stopping.
(2) It may be more parsimonious to 
explain impaired motivation as a symptom of chronic cannabis intoxication and dependence than to invent a new syndrome.
(2,3)
Flashbacks
There are case reports of users experiencing cannabis ‘ﬂ  ashbacks’ , 
i.e. symptoms of cannabis intoxication days or weeks after the individual last used cannabis.
(20) Because of their rarity, and the 
fact that many affected individuals have also used other drugs, it is 
difﬁ cult to decide whether these are rare events that are coinciden-
tal with cannabis use, the effects of other drugs that are often taken 
together with cannabis, rare consequences of cannabis use that 
only occur at much higher than usual doses, experiences that require unusual forms of personal vulnerability, or the results of

only occur at much higher than usual doses, experiences that require unusual forms of personal vulnerability, or the results of 
interactions between cannabis and other drugs.
(2)
Behavioural effects in adolescence
There has been understandable societal concern about the effects of rising rates of cannabis use among adolescents on their school 
performance, mental health and adjustment, and their use of other more hazardous illicit drugs.
(3,21)
There is a strong cross-sectional association between heavy 
cannabis use in adolescence and the risk of discontinuing ahigh-school education and experiencing job instability in young 
adulthood.(20,22)  However, in longitudinal studies the strength of

adulthood.(20,22)  However, in longitudinal studies the strength of 
this association is reduced but not eliminated when statistical adjustments are made for the fact that heavy cannabis users have lower academic aspirations and poorer high-school performance prior to using cannabis than their peers.
(22)
There is some evidence that heavy cannabis use has adverse 
effects upon family formation, mental health, and involvement in drug-related crime.
(3) In each case, the strong associations in cross-
sectional studies are more modest in longitudinal studies after statistically controlling for associations between cannabis use and other pre-existing characteristics which independently predict these adverse outcomes.
(22) It remains uncertain to what degree 
these modest relationships represent residual confounding(22) or 
real relationships.

A consistent ﬁ  nding in the United States(23) has been the regular 
sequence of initiation into drug use, in which cannabis use has typi-cally preceded involvement with ‘harder’ illicit drugs such as stimu-lants and opioids. The interpretation of this sequence of events remains controversial.
(24) There is support for two hypotheses: (i) there 
is a selective recruitment into cannabis use of non-conforming ado-lescents who have a propensity to use a variety of other illicit drugs and (ii) once recruited to cannabis use, it is the social interaction with drug-using peers and greater access to illicit drug markets that increases the likelihood of using other illicit drugs.
(23)
A major public health challenge will be ﬁ  nding effective ways of

(23)
A major public health challenge will be ﬁ  nding effective ways of 
explaining the mental health risks of cannabis use to young people. In addition to a possible increased risk of psychosis, young people also need to be informed about the risks of developing dependence on cannabis, impairing their educational attainment, and possibly increasing their risk of depression.
(21)
School-based drug education programmes produce small, statis-
tically signiﬁ  cant reductions in cannabis use but their primary 
effect is on knowledge rather than behaviour change and most reductions in use occur among less frequent users rather than the heavier users who are at greater risk of adverse mental health effects.
(25,26)
Summary
The major adverse acute psychological effects of cannabis use are as follows:
X Anxiety, dysphoria, panic, and paranoia, especially in naive users
X Impairment of attention, memory, and psychomotor perfor-
mance while intoxicated

X An increased risk of accident if an intoxicated person attempts to 
drive a vehicle.
The major psychological effects of daily heavy cannabis use 
over many years remain contested but probably include the following:
(3)
X A cannabis-dependence syndrome
X Subtle forms of cognitive impairment that affect attention and 
memory and which persist while the user remains chronically intoxicated
X Impaired educational achievement in adolescents with a history 
of poor school performance, whose achievement may be limited

509
by the cognitive impairments produced by chronic intoxication 
with cannabis
X Among those who initiate cannabis use in the early teens, a higher 
risk of progressing to heavy cannabis and other illicit drug use, and becoming dependent on cannabis.
Some useful books
Castle, D.J. and Murray, R.M. (2004). Marijuana and madness . Cambridge 
Hall, W.D. and Pacula, R.L. (2003). Cannabis use and dependence: public 
health and public policy . Cambridge University Press, Cambridge.
Iversen, L. (2000). The science of marijuana . Oxford University Press, 
Oxford.
Kandel, D.B. (2002). Stages and pathways of drug involvement: examining the 
gateway hypothesis . Cambridge University Press, New Y ork.
Roffman, R.A. and Stephens, R.S. (2006). Cannabis dependence: its nature, 
consequences and treatment . Cambridge University Press, Cambridge.
Solowij, N. (1998). Cannabis and cognitive functioning . Cambridge 

Some useful websites
Commonwealth of Australia Department of Health and Ageing.
http://www.health.gov.au/internet/wcms/publishing.nsf/Content/
health-pubhlth-publicat-mono.htm (A monograph reviewing the health effects of cannabis that is periodically updated)
European Monitoring Centre for Drugs and Drug Addiction.
http://www.emcdda.europa.eu/ (Regularly reports data on patterns of 
cannabis use and cannabis related harm in Europe including treatment seeking)
National Drug and Alcohol Research Centre (Australia). http://ndarc.med.
unsw.edu.au/ (This site includes research and resources on the health effects of cannabis and the treatment of cannabis dependence)
National Institute on Drug Abuse (USA). http://www.nida.nih.gov/ 
(Provides regular research updates on the effects of cannabis and the

(Provides regular research updates on the effects of cannabis and the 
treatment of cannabis dependence)
Substance Abuse and Mental Health Services Administration (USA). 
http://www.samhsa.gov/(Provides regular updates of USA survey data on patterns of cannabis use)
Trimbos-Instituut/Netherlands Institute of Mental health and Addiction. 
http://www.trimbos.nl/ (A useful source for research on cannabis use and dependence in the Netherlands)
United Nations Ofﬁ  ce on Drugs and Crime (Vienna). World drug report.
http://www.unodc.org/pdf/WDR_2006/wdr2006_volume1.pdf. (A very 
useful overview of global trends in cannabis use and the global 
cannabis market)
World Health Organization. http://www.who.int/substance_abuse/
publications/psychoactives/en/index.html (This containsauthoritative reviews of the health effects of cannabis that are periodically updated)

 1. Adams, I.B. and Martin, B.R. (1996). Cannabis: pharmacology and 
toxicology in animals and humans. Addiction ,91, 1585–614.
 2. Hall, W.D., Degenhardt, L., and Lynskey. M.T. (2001). The health and 
psychological effects of cannabis use . Commonwealth Department of 
Health and Aged Care, Canberra.
 3. Hall, W.D. and Pacula, R.L. (2003). Cannabis use and dependence:
public health and public policy . Cambridge University Press,
Cambridge. 4. Chen, K. and Kandel, D.B. (1995). The natural history of drug use 
from adolescence to the mid-thirties in a general population sample. 
American Journal of Public Health ,85, 41–7.
 5. Kandel, D.B. and Davies, M. (1992). Progression to regular marijuana 
involvement: phenomenology and risk factors for near-daily use. In Vulnerability to drug abuse  (ed. M.D. Glantz), pp. 211–53. American

involvement: phenomenology and risk factors for near-daily use. In Vulnerability to drug abuse  (ed. M.D. Glantz), pp. 211–53. American 
 6. Ramaekers, J.G., Berghaus, G., van Laar, M., et al. (2004). Dose related 
risk of motor vehicle crashes after cannabis use. Drug and Alcohol 
Dependence ,73, 109–19.
 7. Lichtman, A.H. and Martin, B.R. (2006). Understanding the 
pharmacology and physiology of cannabis dependence. In Cannabis
dependence: its nature, consequences and treatment  (eds. R.A. Roffman 
and R.S. Stephens), pp. 37–57. Cambridge University Press, Cambridge, New Y ork.
 8. Babor, T. (2006). The diagnosis of cannabis dependence. In Cannabis
and R.S. Stephens), pp. 21–36. Cambridge University Press, 
Cambridge, New Y ork.
 9. Anthony, J.C., Warner, L., and Kessler, R. (1994). Comparative

 9. Anthony, J.C., Warner, L., and Kessler, R. (1994). Comparative 
epidemiology of dependence on tobacco, alcohol, controlled substances and inhalants: basic ﬁ  ndings from the National Comorbidity Survey. 
Experimental and Clinical Psychopharmacology ,2, 244–68.
10. Roffman, R.A. and Stephens, R.S. (2006). Cannabis dependence: its 
nature, consequences and treatment . Cambridge University Press, 
11. Hall, W.D. and Degenhardt, L. (2004). Is there a speciﬁ  c cannabis 
psychosis? In Marijuana and madness  (eds. D.J. Castle and 
R.M. Murray), pp. 89–100. Cambridge University Press, Cambridge.
12. Hall, W.D. and Degenhardt, L. (2006). What are the policy implications 
of the evidence on cannabis and psychosis? Canadian Journal of 
Psychiatry. La Revue Canadienne de Psychiatrie ,51, 15–23.
13. Arseneault, L., Cannon, M., Witton, J., et al. (2004). Causal association

13. Arseneault, L., Cannon, M., Witton, J., et al. (2004). Causal association 
between cannabis and psychosis: examination of the evidence. 
The British Journal of Psychiatry ,184, 110–7.
14. Caspi, A., Mofﬁ  tt, T.E., Cannon, M., et al. (2005). Moderation of 
the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol- O-methyltransferase gene: 
longitudinal evidence of a gene X environment interaction. Biological 
Psychiatry ,57, 1117–27.
15. Gottesman, I.I. (1991). Schizophrenia genesis: the origins of madness .
W.H. Freeman, New Y ork.
16. Jeffery, D.P ., Ley, A., and McLaren, S.N.S. (2004). Psychosocial 
treatment programmes for people with both severe mental illness and substance misuse. The Cochrane Database of Systematic Reviews ,
2000, CD001088.
17. Solowij, N. (1998). Cannabis and cognitive functioning . Cambridge 

18. Pope, H.G. Jr, Gruber, A.J., Hudson. J.I., et al. (2003). Early-onset 
cannabis use and cognitive deﬁ  cits: what is the nature of the 
association? Drug and Alcohol Dependence ,69, 303–10.
19. Cohen, S. (1982). Cannabis effects upon adolescent motivation. 
Marijuana and youth: clinical observations on motivation and learning .
National Institute on Drug Abuse, Rockville, MD.
20. Edwards, G. (1983). Psychopathology of a drug experience. The British 
Journal of Psychiatry ,143, 139–42.
21. Hall, W.D. (2006). Cannabis use and the mental health of young 
people. Australian and New Zealand Journal of Psychiatry ,40, 105–13.
22. Macleod, J., Oakes, R., Copello, A., et al. (2004). Psychological and 
social sequelae of cannabis and other illicit drug use by young people: 
a systematic review of longitudinal, general population studies. 
Lancet ,363, 1579–88.

23. Kandel, D.B. (2002). Stages and pathways of drug involvement: 
examining the gateway hypothesis . Cambridge University Press, 
New Y ork.4.2.3.7 the mental health effects of cannabis use

SECTION 4  clinical syndromes of adult psychiatry 510
24. Hall, W.D. and Lynskey, M. (2005). Is cannabis a gateway drug? 
T esting hypotheses about the relationship between cannabis use and 
the use of other illicit drugs. Drug and Alcohol Review ,24, 39–48.
25. White, D. and Pitts, M. (1998). Educating young people about drugs: a 
systematic review. Addiction ,93, 1475–87.
26. T obler, N.S., Lessard, T., Marshall, D., et al. (1999). Effectiveness of 
school-based drug prevention programs for marijuana use. School
Psychology International ,20, 105–37
4.2.3.8 Nicotine dependence 
and treatment
T obacco use is the single most important preventable health risk in 
the developed world, and an important cause of premature death worldwide.
(1) Smoking causes a wide range of diseases, including 
many types of cancer, chronic obstructive pulmonary disease, coronary heart disease, stroke, peripheral vascular disease, and peptic ulcer disease.

(2) According to the World Health Organization 
(WHO) smoking prevalence is estimated at around 28.6 per cent (40 per cent among males and 18.2 per cent among females),
(3)
it is therefore the most prevalent form of drug dependence in the world.
T obacco causes around 13 500 deaths per day, currently, approxi-
mately 5 million people are killed annually by tobacco use. In the last few years the standardized death rate for lung cancer among men across the European region has fallen but it has increased in women.
(3) By 2030, estimates based on current trends indicate that 
this number will increase to 10 million, with 70 per cent of deaths occurring in low- and middle-income countries.
(4)
T obacco remains the leading contributor to the disease burden

(4)
T obacco remains the leading contributor to the disease burden 
in the majority of the developed countries. According to the WHO tobacco-related health care costs between 1 per cent and 1.1 per cent of Gross Domestic Product (GDP) in many countries.
(5,6)
 Despite the considerable efforts made to ﬁ  ght smoking in the 
last few decades, there are still substantial number of people who, in full knowledge of the health hazards, begin smoking or continue smoking. Since 2002 many countries have implemented smoke-free policies, strengthening product regulation, restrictions on smoking in public places and in work places, which for the ﬁ  rst 
time are extended to bars and restaurants.
(7)
Traditionally, experimentation with and the initiation of the

(7)
Traditionally, experimentation with and the initiation of the 
smoking habit were related to issues such as rebellious adolescent behaviour, a need to afﬁ  rm maturity, challenging authority, imitat-
ing idols, peer group pressure (from friends or relatives who are smokers) and associating smoking with being successful from a professional, ﬁ  nancial, or sexual point of view. More recently, 
other perspectives, such as the speciﬁ  c personality pattern typiﬁ  ed 
by the search for challenges (sensation seeking behaviour) and the characteristics of neuropsychological development, also began to be considered.
(8)An other important issue is that smokers are 
much more likely than non-smokers to use or even to abuse other psychoactive drugs. Over 90 per cent of alcoholic persons smoke, drink more coffee, or take other drugs like cannabis, cocaine, or amphetamines. The reasons that smokers have such difﬁ  culty

in ceasing smoking are probably similar to those of organic dependence.
(9–11)
Cigarette smoking and nicotine dependence
Approximately one-third of those individuals who experiment with cigarettes become regular smokers.
(12) Once dependence 
develops, tobacco addiction can become a chronic relapsing disor-der with direct and serious medical consequences.
(13)
Nicotine dependence explains why approximately 70 per cent of 
smokers who want to quit smoking do not succeed. Of these, approximately one-third succeed for only 1 day and less than 10 per cent remain abstinent for 12 months.
(13) The deﬁ  nitive cessation 
of smoking generally occurs only after various attempts, and the relapse rate is very high, 88 per cent.
(14) The percentage of smokers 
in which relapse occurs is similar in almost all social classes, even when including individuals, such as health care professionals, who are more informed about tobacco-related diseases.

On the other hand, only a portion of smokers develop such 
dependence. Why is it that not all smokers follow the same course? This question about smoking relates to the wider one of why only some people exposed to drugs become addicted to them.
(15)
Why is nicotine so addictive?
The psychoactive component of tobacco is nicotine, which has its central nervous system effects by acting as agonist at the nicotine subtype of acetylcholine receptors. About 25 per cent of the nicotine inhaled when smoking a cigarette reaches the blood, and reaches the brain in about 15 s. The half-life of nicotine is about 2 h.
(13)
Nicotine is believed to have positive reinforcing and addictive

(13)
Nicotine is believed to have positive reinforcing and addictive 
properties because it activates the dopaminergic pathway project-ing from the ventral tegmental area to the cerebral cortex and the limbic system, the system that is affected by cocaine and amphet-amine. In addition to activating the reward system, nicotine causes an increase in the concentrations of circulating norepinephrine and epinephrine, and increased release of vasopressin, β-endorphin, 
adrenocorticothropine, and cortisol.
(16)
The development of dependence is enhanced by strong social 
factors that encourage smoking in some settings.(17)
Other central effects
The stimulatory effects of nicotine result in improved attention, learning, reaction time, and problem-solving ability. Nicotine also decreases psychological tension and lessens depressive feelings.
The effects of nicotine in the cerebral blood ﬂ  ow (CBF) have

The effects of nicotine in the cerebral blood ﬂ  ow (CBF) have 
been studied and results suggest that short-term nicotine exposure increases the CBF without changing cerebral oxygen metabolism but that long-term nicotine exposure is associated with decrease in the CBF.
(18)
Genetic issues
Epidemiological studies have shown that the genetic component can play a signiﬁ  cant role in the smoking habit, being responsible 
for 40 per cent to 60 per cent of the variability in the risk of addiction.
(19,20) The ﬁ  rst studies relating genetics to smoking date 
from 1958(21) when it was suggested that there were genes that, in

511
youth, predispose individuals to become smokers and, later, to 
present with lung cancer.(21)
Many twin concordance studies have indicated that genetic 
inheritance plays a role in smoking addiction.(22) Such studies have 
demonstrated a higher concordance rate in relation to smoking 
among monozygotic twins than among dizygotic twins, whether raised together or separately.
(23,24) More recent studies with larger 
study samples, a better classiﬁ  cation of phenotypes, and more 
sophisticated statistical models, point to a rather signiﬁ  cant inﬂ  u-
ence of the genome in determining the smoking phenotype.(25)
The most extensively studied genes of the dopaminergic pathway 
are those that regulate the ﬂ  ow of dopamine in the central nervous

are those that regulate the ﬂ  ow of dopamine in the central nervous 
system. Five different dopamine receptors are known, and the genes that encode them have been cloned (DRD1, DRD2, DRD3, DRD4, and DRD5). Among those, the DRD2 receptor has been studied most widely, because of its association with other addictive behav-iours, and because nicotine has a dopamine-releasing effect.
(26–28)
Smoking in psychiatric patients
Nicotine has been said to provide anxiety relief, oral gratiﬁ  cation, 
and self-medication of psychotic symptoms in psychiatric patients.
(29) Patients with schizophrenia and severe mental illness 
smoke cigarettes at rates that well exceed the general population.(30)

Little is known about the correlates and sequels of increased smok-ing severity on persons with severe mental illness. Greater smoking severity has however been associated with greater perceived stress, poorer overall subjective quality of life, and lower satisfaction with ﬁ nances, health, leisure activities, and social relationships, results 
that may lend support to a self-medication hypothesis.
(31)
Nicotine intoxication and withdrawal 
symptoms
The primary addictive substance in cigarette smoking is nicotine. 
Cigarette smoking is very efﬁ  cient nicotine delivery system because 
nicotine is nebulized and subsequently absorbed through the extensive pulmonary lung vessels. Consequently, smoking produces high arterial nicotine concentrations.
(12) These high arterial con-

centrations, higher than venous concentrations, deliver a bolus of 1–3 mg of nicotine rapidly to the brain, a few seconds after smoking. With nicotine receptor activation, neurotransmitters are released including dopamine, norepinephrine, serotonin, and endogenous opioids. The immediate positive reinforcing effects of smoking include a reduction in anxiety and increased alertness and 
concentration.
(32)
Nicotine’s half-life is 2 h; therefore, repeated administration is 
needed through the day to maintain its effects. Consequently 
smokers usually smoke at frequent intervals to maintain narrow range of nicotine concentration in the blood. Paradoxically, 
chronic administration of nicotine results in an increase in the 
number of nicotine receptors. This paradoxical effect is probably

number of nicotine receptors. This paradoxical effect is probably 
due to a chronic nicotine receptor desensitization and inactivation. An increased number of receptors may play a role in the withdrawal symptoms that many smokers experience with prolonged cigarette abstinence.
(33)
Nicotine is a highly toxic chemical; doses of 60 mg in adults 
are fatal secondary to respiratory paralysis (an average cigarette has an average dose of 0.5 mg). At low doses, symptoms of toxicity are nausea, vomiting, salivation, pallor due to peripheral vasoconstric-
tion, weakness, abdominal pain, diarrhoea, dizziness, headache, increased blood pressure, tachycardia, tremor, and cold sweats. T oxicity is also associated with inability to concentrate, confusion, and sensory disturbances. During pregnancy, smoking is associated with an increased incidence of low-weight-birth babies.
(32)

(32)
DSM-IV does not have a diagnostic category for nicotine intoxi-
cation; however, it has a category for nicotine withdrawal.(34)
ICD-10 does have a category for nicotine intoxication (F17.0, mental and behavioural disorders due to use of tobacco, acute intoxication).
(35) Withdrawal symptoms can develop within 2 h 
after having smoked the last cigarette. Withdrawal symptoms include dysphoria and depressed mood, insomnia, irritability, anxiety, frustration, difﬁ  culty in concentration and increase in 
appetite, and weight gain. Withdrawal symptoms peak within 24–36 h after cessation and usually diminish after 1 week of absti-nence but can last for much longer. Some individuals continue smoking to avoid the negative symptoms of withdrawal.
(36,37)
Nicotine dependence
The cumulative ﬁ  ndings of more than 2500 scientiﬁ  c papers were 
summarized in the 1988 Surgeons General’s Report on the Health 
Consequences of Smoking: Nicotine Addiction .(38) Nicotine has a

Consequences of Smoking: Nicotine Addiction .(38) Nicotine has a 
pronounced effect on the major stress hormones, and the dose-related effects of nicotine on neuroendocrine responses appear to constitute a critical component of its pharmacological action. Hypothalamic corticotrophin-releasing factor (CRF) is stimulated by nicotine, and levels of hypophyseal hormones including ACTH and arginine-vasopressin are increased in a dose-related manner. At higher doses, growth hormone (GH) and prolactin are entrained, and corticosteroid levels are related to plasma nicotine levels.
(15,39,40)
Treatment for tobacco dependence

Many of the adverse health effects of smoking are reversible, and smoking cessation treatments represent some of the most cost-effective of all health care interventions. Although the greatest beneﬁ  t accrues from ceasing smoking when young, even quitting in 
middle age avoids much of the excess health care risk associated with smoking.
(41–43)
In order to improve smoking cessation rates, effective behavioural 
and pharmacological treatments, coupled with professional coun-selling and advice, are required. Since smoking duration is the principal risk factor for smoking-related morbidity, the treatment goal should be early cessation and prevention of relapse.
(44,45)
The health beneﬁ  ts are various: smoking cessation has a major 
and immediate health beneﬁ  t for persons with or without smoking-

(44,45)
related diseases; former smokers live longer than those who con-tinue to smoke; smoking cessation decreases the risk of lung cancer, myocardial infarction, cerebrovascular diseases, and chronic lung diseases.
(46)
Non-pharmacological treatment
Physician counselling and pharmacotherapeutic interventions for smoking cessation are among the most cost-effective clinical inter-ventions. Several strategies can be used for smoking cessation, counselling differs according to the patient’s readiness to quit.For smokers who do not intend to quit smoking, physicians should 4.2.3.8 nicotine dependence and treatment

SECTION 4  clinical syndromes of adult psychiatry 512
inform and sensitize them about tobacco use and cessation. For 
smokers ready to quit, the physician should show strong support, help set a quit date, prescribe pharmaceutical therapies for nicotine dependence, if needed.
(47,48)
There is insufﬁ  cient information to know which elements of 
behavioural support are effective or whether one approach, such as motivational interviewing or cognitive behavioural therapy, is more effective than another. There is some evidence to suggest that group support may be more effective in general than one-to-one support
(49) and that it should involve multiple sessions.(50) There is 
also evidence that such sessions can be effective even if conducted over the telephone.
(51)
Of the many web-based support packages available on the 
Internet, only two have been evaluated in randomized controlled trials,
(52,53) these trials of tailored programmes enrolled smokers

(51)
(52,53) these trials of tailored programmes enrolled smokers 
who were using nicotine replacement. Both trials showed signiﬁ  -
cant beneﬁ  ts 10–12 weeks after the quit date.
There are a few adequate studies examining complementary 
therapies in smoking cessation. Meta-analysis of trials of acupunc-ture and hypnotherapy showed no beneﬁ  t but could not exclude 
small effects.
(54,55)
Nicotine replacement therapies
Nicotine replacement therapies (NRTs) were designed in order to enhance efﬁ  cacy rates during smoking cessation by replacing some 
of the nicotine usually delivered by smoking. All replacement therapies have shown to have high rates of efﬁ  cacy. The choice 
of NRT depends on patient’s preference, side effects, presence of concomitant medical conditions, and a history of previous success or failure.
(56,57)

(56,57)
(a) Nicotine gum and nicotine lozenge
Nicotine gum was the ﬁ  rst NRT marketed for smoking cessation, 
contains nicotine bound to an iron resin. The nicotine is slowly released into the mouth and is absorbed through the mucosa of the mouth, only 50 per cent of the nicotine in a piece of gum is systemically absorbed and concentrations reach a maximum peak in 30 min after onset of chewing.
(12) The staring dose for individu-
als who smoke 20 cigarettes a day should be 2 mg. The gum should not be prescribed in patients with temporo-mandibular joint dis-ease and those with dental or oral problems. The nicotine lozenge contains nicotine bound to a prolacrilex ion-exchange resin, does not require chewing and therefore is preferable to the gum for patients with dental problems.
(58)
(b) Transdermal nicotine

(58)
Transdermal nicotine, commonly known as the nicotine patch, produces a constant delivery of nicotine that is very useful for patients with poor treatment adherence. Eight weeks of treatment are generally sufﬁ  cient for smoking cessation.
(59)
Transdermal nicotine is available in a variety of formulations 
and dosing schedules (i.e. 15 mg/16 h; 7, 14, 21 mg/24 h). Peak nic-otine concentrations for the various systems are reached 2–6 h after application and steady state conditions occur 2–3 days after contin-ued patch use.
(59)
(c) Nicotine nasal spray and inhaler
Nicotine nasal spray delivers nicotine through the nasal mucosa. One advantage is that it relieves tobacco cravings quickly. It is avail-able only by prescription. One spray to each nostril constitutes a dose, approximately 1 mg nicotine. Patients should use one or two 
doses per hour; the nasal spray delivers nicotine rapidly, with venous nicotine peaking at 5–10 min after administration.

(60) Side 
effects include some initial irritation of the nasal mucosa should be 
avoided in patients with rhinitis, nasal polyps, or sinusitis.
Nicotine vapour inhaler is used by pufﬁ  ng through a cartridge 
inhaler, and may be useful for smoking cessation in some patients because its use is similar to the smoking ritual, and it delivers nico-tine rapidly. It is only available by prescription. The recommended treatment period is up to 24 weeks.
(45)

(45)
Considering that not all smokers respond well to nicotine replace-ment therapies and some smokers have comorbid symptoms there has been considerable interest in non-nicotine medications to treat nicotine dependence. The observations that some antidepressant-like bupropion and other selective serotonin-reuptake inhibitors (SSRIs) are useful as a treatment for smoking cessation, led to intensive research to study dopamine, serotonin, norepinephrine, glutamate, gamma-aminobutyric acid (GABA), nicotine, cannabi-noid, and opiod receptors.
(61,62)
Sustained-released bupropion
The sustained-released bupropion is currently considered as a ﬁ  rst-
line treatment for cigarette smokers. The mechanism of action of this antidepressant in the treatment of nicotine dependence likely involves blockade of dopamine and norepinephrine reuptake as well as antagonism of high-affinity nicotine acetylcholine receptors.
(63)

(63)
The goals of bupropion therapy for nicotine dependence are 
(1) cessation of smoking behaviour and (2) reduction of nicotine withdrawal symptoms. In addition, bupropion SR may delay cessation-induced weight gain.
(64)
A study by Hurt et al .(65) established the efﬁ  cacy and safety of 
bupropion SR for treatment of nicotine dependence, and led to its approval for this indication by the FDA in 1998. Bupropion treatment also reduces weight gain associated with smoking cessa-tion and signiﬁ  cantly reduced nicotine withdrawal symptoms at a 
dose of 150–300 mg/day. Major side effects are headache, dry mouth, nausea, vomiting, and insomnia.
(65)
Nortrityline
This tricycle antidepressant appears to have efﬁ  cacy rates similar to 
bupropion in smoking cessation.(66) The mechanism of action is

(65)
bupropion in smoking cessation.(66) The mechanism of action is 
thought to be related to its noradrenergic and serotoninergic reup-take blockade. Side effects are those of the typical tricyclic antide-pressants and include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortryptiline has been recommended as a second-line treatment.
(61,67)
Clonidine
Because clonidine appears to have some efﬁ  cacy for alcohol and 
opioid withdrawal, it has been evaluated for the treatment of nico-tine withdrawal. However, it has not proved to be as effective as other therapies. Several clinical trials used oral or transdermal clonidine in doses of 0.1–0.4 mg/day for 2–6 weeks with or without behaviour therapy. Most common side effects of clonidine are dry mouth, sedation, and constipation, postural hypotension, and depression.
(61)

513
Selective serotonin reuptake inhibitors
The available evidence provides little support for the use of SSRIs 
to assist in smoking cessation, either alone or in combination with other therapies. Placebo-controlled trials of ﬂ  uoxetine or paroxetine 
failed to show an increase in smoking cessation.
(61)
Varenicline
Varenicline is a selective alpha (4) beta (2) nicotinic acetylcholine recep-tor partial agonist and the ﬁ  rst non-nicotine-containing medication 
developed with the sole purpose of treating nicotine addiction.
(68)
Varenicline seems to be more efﬁ  cacious than bupropion 24 weeks 
after randomization to a 12-week treatment course and 1 year after randomization in an identical trial. There are no contraindications except hypersensitivity and the drug is generally well tolerated. Varenicline, which is recently approved for smoking cessation,

offers an option to patients who cannot tolerate the adverse effects associated with nicotine-replacement therapy and bupropion. It is also an alternative to consider for patients with contraindications to such therapies. Varenicline is completely absorbed orally and not affected by food. Steady state is reached within 4 days of 
administration.
(69,70)
Other pharmacological treatments
Several new therapies are emerging as possible treatment options for smoking cessation. Rimonabant, a selective cannabinoid antagonist, blocks dopamine release in the nucleus accumbens, a primary reward centre for the brain. Studies have found that Rimonabant may not only be effective as a smoking cessation aid but may also assist in the maintenance of nicotine abstinence. Rimonabant has also demonstrated a weight-loss beneﬁ  t, which 
may be attractive to smokers concerned with weight gain associated with smoking cessation.
(71–73)
Three nicotine vaccines are currently in development, each

(71–73)
Three nicotine vaccines are currently in development, each 
acting to sequester nicotine from the bloodstream, thereby pre-venting its penetration of the central nervous system. Ongoing studies will evaluate their use as established therapies for smoking cessation.
(74,75)
Despite the reality that smoking remains the most important preventable cause of death and disability, most clinicians under-perform in helping smokers quit. Nearly 70 per cent of smokers want to quit, and 42.5 per cent attempt to quit each year. The most effective smoking cessation programmes involve a combination of pharmacotherapy and behavioural and/or cognitive counselling to improve abstinence rates. Ways to counter clinicians’ pessimism about cessation include the knowledge that most smokers require multiple attempts before they succeed in quitting.

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Pharmacology & Therapeutics ,19(3), 205–9.
68. Stack, N.M. (2007). Smoking cessation: an overview of treatment 
options with a focus on varenicline. Pharmacotherapy ,27(11), 1550–7.
69. Potts, L.A. and Garwood, C.L. (2007). Varenicline: the newest agent 
for smoking cessation. American Journal of Health-System Pharmacy ,
64(13), 1381–4.
70. T onstad, S., Tønnesen, P ., Hajek, P ., et al. (2006). For the varenicline 
phase 3 study group. Effect of maintenance therapy with varenicline 
on smoking cessation: a randomized controlled trial. The Journal of the 
American Medical Association ,296, 64–71.
71. Garwood, C.L. and Potts, L.A. (2007). Emerging pharmacotherapy’s 
64(16), 1693–8.

72. Fowler, J.S., Volkow, N.D., Wang, G.J., et al. (1996). Brain monoamine 
oxidase. An inhibition in cigarette smokers. Proceedings of the National 
Academy of Sciences of the United States of America ,93(24), 14065–9.
73. Markou, A., Paterson, N.E., and Semenova, S. (2004). Role of 
gamma-aminobutyric acid (GABA) and metabolic glutamate receptors in nicotine reinforcement: potential pharmacotherapy for smoking 
cessation. Annals of the New York Academy of Sciences ,1025 , 491–503.
74. Dwoskin, L.P ., Joyce, B.M., Zheng, G., et al. (2007). Discovery of a novel 
nicotinic receptor antagonist for the treatment of nicotine addiction: 1-(3-Picolinium)-12-triethylammonium-dodecane dibromide (TMPD). Biochemical Pharmacology ,74(8), 1271–82. Epub 
21 July 2007.

75. Oliver, J.L., Pashmi, G., Barnett, P ., et al. (2007). Development of an 
anti-cotinine vaccine to potentiate nicotine-based smoking cessation strategies. Vaccine ,25(42), 7354–62. Epub 30 August 2007.
4.2.4 Assessing need and 
organizing services for drug misuse problems
John Marsden, Colin Bradbury, and John Strang*
In the present decade, there has been substantial investment in drug

In the present decade, there has been substantial investment in drug 
misuse treatment thereby expanding the workforce, the capacity of the treatment system and leading to reduced waiting times and better integration of local services. In 2006–07, an in-treatment population of approximately 200 000 individuals were recorded by the National Drug Treatment Monitoring System (NDTMS). Capture-recapture estimates suggest that there are approximately 327 000 users of opioids and/or crack cocaine.
About two-thirds of adults entering drug misuse treatment
services are dependent on illicit heroin—a clinical presentation complicated by between 20 per cent to 50 per cent of admissions by concurrent dependence on cocaine and other substances such

services are dependent on illicit heroin—a clinical presentation complicated by between 20 per cent to 50 per cent of admissions by concurrent dependence on cocaine and other substances such 
as the misuse of pharmaceutical medications (such as benzodiaze-pines). Cannabis is reported as the main problem drug for younger patients under 18 years of age. Overall, treatment services forclients of all ages are able to assess and provide interventionsacross all illicit drugs including amphetamine-type stimulants, sedative/hypnotics, cannabis, hallucinogens and volatile substances (solvents and inhalants). Hazardous and harmful alcohol use char-acterizes a signiﬁ  cant, but priority group of drug misuse treatment 
seekers.
In 2006, a revised national drug misuse treatment effectiveness

seekers.
In 2006, a revised national drug misuse treatment effectiveness 
strategy stressed the need for better local partnerships tocommission and organize local services and promote reintegration of treated patients into the community. A core component ofthe strategy was the creation of Criminal Justice IntegratedT eams (CJITS) who were given the role of treatment case coordi-nation for individuals involved in the justice system withidentiﬁ  ed drug misuse. Nevertheless, improvements to the reach, 
operation, and effectiveness of treatments remains a priority—particularly tackling high-risk behaviours linked to the acquisition and transmission of blood-borne infections and ensuring thatall service users receive good quality assessment and care
coordination.
Local coordination of treatment
Drug Action T eams (DATs) were originally set up in 1995 under a

Drug Action T eams (DATs) were originally set up in 1995 under a 
Government white paper on drug misuse. The purpose of the DAT was to co-ordinate the activity and spend of local statutary com-missioning agencies who have an interest in reducing the harm caused by illicit drug use to individuals, their families, and the com-munity. DATs and their membership typically consists of senior commissioning representatives from local Police, Health, Local Authority and Probation services. Increasingly, the Prison Service are represented following the announcement of a new Integrated Drug Treatment System for prisoners which seeks to ensure that the same appropriate and evidenced drug treatment interventions are available to individuals regardless of whether they are in prison or in the community. Under the Police Reform Act (2002), the pro-cess of combining the activity of DATs with their equivalent bodies

for crime (Crime and Disorder Reduction Partnerships (CDRPs) 
was started. Local areas organize their activity in differing ways, but the concept of co-ordination of action between the DAT and CDRP is now universal.
DATs are charged with consulting with and involving local com-
munities, stakeholders, treatment providers, and crucially—users and carers—in the development of their local commissioning strategies. DATs are allocated a hypothecated fund for improving capacity and quality of drug treatment services for their residents. This Pooled Treatment Budget is typically banked by a partner agency (usually the PCT) but is intended to be commissioned jointly (along with mainstream monies that partner agencies allocate for drug treatment) via the DAT Partnership structure. DAT Partnerships typically have a sub-group know as the Joint Commissioning Group (JCG) which seeks to operationalize the DAT’s agreed strategy for the locality.

The National Treatment Agency for Substance Misuse (NTA) is
a Special Health Authority set up in 2001 to oversee and perfor-mance manage the commissioning of effective drug treatment. 
* The views expressed in this chapter are those of the authors and do 
not necessarily reﬂ  ect the views of the National Treatment Agency. The 
commissioning, performance management and planning of drug treatment varies signiﬁ  cantly across the United Kingdom. Unless stipulated to the 
contrary, the following text applies speciﬁ  cally to England.4.2.4 assessing need and organizing services for drug misuse problems

SECTION 4  clinical syndromes of adult psychiatry 516
DAT Partnerships submit a treatment plan on an annual basis 
which is signed off by the NTA and other regional partners and performance monitored on a quarterly basis. Since 2005–06, the NTA has issued guidance on conducting a Needs Assessment for the local population and increasingly assessment of need is being seen as the centrepiece of DAT Partnership commissioning activity. DAT Partnerships are encouraged to set up expert groups which (in combination with available local data sources of prevalence and treatment) should be used to carefully consider available information and intelligence in order to inform the local Joint Commissioning Group of assessed levels of unmet need, therefore enabling them to set and update commissioning priorities on a cyclical basis.
Types of treatment

In the UK, treatment for substance use disorders vary on several core dimensions, as follows: (a) setting (outpatient/community or inpatient/residential), modality (pharmacological or behavioural); (b) content (e.g. cognitive behavioural therapy, motivational approaches, contingency management; couples therapy); (c) goals (harm reduction, partial or complete abstinence); (d) intensity (brief interventions or intensive therapeutic contact); (e) extent of external contingency (e.g. self-referral or criminal justice mandate); and (f) type of provider (NHS, non-governmental orga-niztion and private/commercial). In 2002, the NTA promulgated a national service framework for drug misuse services and updated this four years later. The framework uses a practical framework to aid rational and evidence-based commissioning of drug treatment in England with services for drug misusers grouped into four broad 
bands, or tiers.
Tier 1 interventions

This ﬁ  rst tier involves the provision of information, advice, screen-
ing and referral to drug users by generic medical and social care services (e.g. Accident and Emergency Departments, community retail pharmacies). It includes liaison and partnership working with specialist drug treatment services to provide speciﬁ  c interven-
tions (e.g. treatment of patients with health problems caused by Hepatitis C infection).
Tier 1 services for adults are not structured drug or alcohol 
treatment, but can be part of the local substance misuse treat-ment system. These services work with a wide range of clients including drug and alcohol misusers, but their sole purpose is not drug or alcohol treatment. Tier 1 services comprise a range of interventions which are not drug-speciﬁ  c, but offer a variety 
of generic health and social care interventions. In this context, 
the role of Tier 1 includes the provision of their own services

the role of Tier 1 includes the provision of their own services 
plus, as a minimum, screening drug misusers and referral tolocal drug and alcohol treatment services in Tiers 2 and 3. Tier 1 provision for drug and alcohol misusers may also includeassessment, services to reduce drug-related harm, and liaisonor joint working with Tiers 2 and 3 specialist drug and alcohol treatment services. Tier 1 services are crucial to providingservices in conjunction with more specialized drug and alcohol services (e.g. general medical care for drug mis users in commu-nity-based or residential substance misuse treatment, or housing support and aftercare for drug misusers leaving residential care or prison).Tier 2 interventions
The second tier describes interventions involving speciﬁ  c drug-

related information and advice to help drug users reduce or avoid hazardous and harmful patterns of use or attain and maintain abstain harm. Services are delivered from dedicated community locations as well as outreach and may also include brief, structured psychosocial interventions, various harm minimization interven-tions (including syringe and needle exchange) and aftercare sup-port. Tier 2 services may also provide triage assessment and linked referral to structured drug treatment and in this respect may oper-ated independently or in the same setting as a Tier 3 intervention team. Tier 2 interventions for adults provide accessible drug and alcohol specialist services for a wide range of drug and alcohol misusers referred from a variety of sources, including self-referrals. This tier is deﬁ  ned by its low threshold to access services, and lim-
ited requirements on drug and alcohol misusers to receive services.

ited requirements on drug and alcohol misusers to receive services. 
Often drug and alcohol misusers will access drug or alcohol 
services through Tier 2 and progress to higher tiers. Tier 2 inter-ventions include advice and information, drop-in services, needle exchange and motivational interviewing.
Tier 3 interventions
In terms of the volumes of people receiving treatment, this tier is at the centre of the system. It includes specialized care-planned pharmacotherapy (opioid agonist and antagonist and adjunctive medication prescribing to treat dependence) and a broad array of psychosocial interventions delivered by combined or separate teams in the community and primary care. There is an emphasis 
on high-quality assessment, care planning, liaison and review and regular contact with a clinical keyworker and other team members.

on high-quality assessment, care planning, liaison and review and regular contact with a clinical keyworker and other team members. 
The frequency of scheduled contact varies widely across Tier 3 ser-vices but is particularly indented to be intensive among users attending ‘structured day programmes’ . Tier 3 interventions for adults are provided solely for drug and alcohol misusers in structured programmes of care. Tier 3 structured services include psychotherapeutic interventions and structured counselling (e.g. cognitive behavioural therapy, motivational interventions), metha-done maintenance programmes, community detoxiﬁ  cation, or day

care provided either as a drug- and alcohol-free programme or as an adjunct to methadone treatment. Community-based aftercare programmes for drug and alcohol misusers leaving residential rehabilitation or prison are also included in Tier 3 interventions. There is interest in developing behaviour therapies to treatment drug dependence on contingency management. Psychoactive sub-stances can exert unconditioned reinforcing effects and repeated 
administration produce several conditioned responses. For exam-
ple, voucher-based reinforcement therapy uses vouchers of increas-ing value for goods and services with various bonus incentives to subjects who can provide drug-free urine tests. The National Institute for Health and Clinical Excellence (NICE) has produced guidelines for the effective delivery of various psychosocial treat-ment interventions tailored to the needs of drug misusers, includ-ing brief motivational interventions, contingency management and behavioural couples therapy.

Tier 4 interventions
The fourth tier of the treatment system denotes specialist inpatient (and general ward) inpatient services providing stabilization and

517
medically supervised withdrawal (detoxification), residential 
rehabilitation programmes (providing psychosocial and practical, vocational supports designed to maintain abstinence and promote long-term recovery) and a range of halfway houses and supportive accommodation. Some inpatient and residential programmes are directly linked. These services vary in duration from brief ( <10 
days), short-term ( <3 months) and long-term ( >3 months). Tier 4 
services are highly structured interventions underpinned by assess-ments and close monitoring of clinical progress. Rehabilitation programmes have been pioneered and then sustained chieﬂ  y in

services are highly structured interventions underpinned by assess-ments and close monitoring of clinical progress. Rehabilitation programmes have been pioneered and then sustained chieﬂ  y in 
the voluntary sector. Some adhere to or have adopted a therapeutic philosophy (e.g. 12-Step based on the Minnesota Model of addic-tion recovery developed in the USA) or therapeutic community model, while others operate as 'general houses’ —which seek tofoster responsible communal living and community reintegration. Tier 4 substance misuse interventions for adults are aimed at indi-viduals with a high level of presenting need and usually require a higher level of commitment from drug and alcohol misusers than is required for services in lower tiers. Tier 4 services are rarely accessed directly by clients. Referral is usually from Tiers 2 or 3 ser-vices or via community care assessment.
NICE has produced guidelines for the delivery of psychosocial

NICE has produced guidelines for the delivery of psychosocial 
interventions in residential rehabilitation services and also for the organization and delivery of opioid detoxiﬁ  cation services.
Commissioning treatment services
The national drugs strategy requires Crime and Drug Partnerships 
to commission services (or ensure access to) structured treatment (Tiers 3 and 4). The balance of lƒocal drug misuse treatment ser-vices and their detailed delivery mechanisms should be tailored to ﬁ t the needs of the local population; commissioners are encour-
aged to think systemically rather than focusing on putting in place individual services. Poorly deﬁ  ned care pathways between services

aged to think systemically rather than focusing on putting in place individual services. Poorly deﬁ  ned care pathways between services 
and the lack of a joined-up care planned approach is clearly an unsatisfactory situation. Many individuals may require the provi-sion of several different types of treatment service over time. It is quite common for an individual receiving treatment from one pro-vider to receive additional welfare support and other social inclu-sion services which are provided by other agencies (e.g. housing support, legal advice). These supports are important elements in an effective package of care services that can evolve over the course 
of an individual’s treatment. T ogether, the four tiers are meant to 
imply a continuum of care. Generic service providers and state agencies can refer an individual both up and down the four tiers to access appropriate treatment or support services.
Needs assessment

In the following section, we use an epidemiologically-based con-ceptualization of population treatment needs to discuss the organi-zation of treatment services and methods for assessing need. Needs assessment occupies an importance place in the evidenc e-based plan-
ning process for the design and delivery of substance misuseservices. It is the systematic collection of information about ageographically deﬁ  ned population and then applying this to make 
changes that will be beneﬁ  cial to health. In the drug misuse ﬁ  eld, 
there is a speciﬁ  c focus on two groups in the community: (a) those 
that are not in contact with services and treatment agencies and have unmet need; (b) those in contact with inefﬁ  cient, ineffective or inappropriate health care services who have unmet need or for

that are not in contact with services and treatment agencies and have unmet need; (b) those in contact with inefﬁ  cient, ineffective or inappropriate health care services who have unmet need or for 
whom outcomes could be improved. Good needs assessment practice involves the application of epidemiological (and some-times spatial geographical) techniques to estimate the number of people in the two groups above, clear understanding of the costs and beneﬁ  ts of interventions, a close collaboration with clinical 
services and the range of community stakeholders, and a planning and evaluation process to effect change. There is active encourage-ment for drug misuse partnerships and commissioners to under-take comprehensive needs assessments in the area of drug misuse with a speciﬁ  c target to assess the needs of young people. However, 
there have been few systematic quantitative and qualitative studies conducted in the drug misuse ﬁ  eld in the UK. In fact, most studies

there have been few systematic quantitative and qualitative studies conducted in the drug misuse ﬁ  eld in the UK. In fact, most studies 
in the mental health service ﬁ  eld have been mainly or exclusively 
qualitative, relying on focus group discussion material. Multiple indicator methods and capture-recapture techniques have enabled estimates to be derived of the number of problem drug users in local areas.
Target groups
At the level of the individual patient, several headline factors may be inﬂ  uential in the assessment and treatment planning process:

At the level of the individual patient, several headline factors may be inﬂ  uential in the assessment and treatment planning process: 
age, gender, race, and culture; pregnancy; familial pattern; quantity, frequency, and route of administration of psychoactive substances used; acute intoxication (overdose liability); extent of impairment and complications; social and occupational environmental supports and stressors—including acute housing need, training, and educa-tion. Complex cases will usually (but not always) be characterized by drug-related impairment, dependence, regular injecting, high tolerance levels and co-morbid problems across physical, psycho-logical and personal/social functioning domains. At the population level, we identify six, non-independent groups. The prevalence of these groups and their case-mix at the local level will have ramiﬁ  ca-
tions for the assessment of health care needs and the planning, com-

missioning, delivery and monitoring of treatment services.
(a) Non-dependent, hazardous substance users
This group comprises individuals who are experiencing drug-related 
problems but they do not meet the criteria for dependence. This group may include large numbers of younger users who have begun to use drugs relatively recently. Because members of this group (both adults and particularly young people) are at risk of advanc-ing their drug involvement to more serious levels they may be ideal clients for early intervention services.
(b) Drug injectors
This group comprises individuals who are injecting drugs and who may be at risk of acquiring and transmitting blood borne diseases. Community surveys suggest that less than 1:3 drug injectors share needles and syringes but 1:2 share injecting equipment (ﬁ  lters, 
spoons and ﬂ  ushing water). Research Individuals who inject drugs

spoons and ﬂ  ushing water). Research Individuals who inject drugs 
are much more likely to be dependent and experience drug-related harms. They constitute a priority group to be attracted to appropriate harm reduction and structured treatment programmes and retained in treatment as appropriate.
(c) Acutely intoxicated drug users
The speciﬁ  c needs of this group are identiﬁ  ed because of the 
morbidity and mortality risks to health due to adverse reactions and drug overdose. This sub-group may overlap with sub-group B 4.2.4 assessing need and organizing services for drug misuse problems

SECTION 4  clinical syndromes of adult psychiatry 518
(the IDU). There is evidence that some two-thirds of heroin users 
have experienced an overdose. Risk of overdose is increased for opiates users who have also consumed other central nervous system depressants—commonly other opiates, alcohol and benzo-diazepines. Preventing drug overdose and overdose mortality is a speciﬁ  c priority area. Acute intoxication is a discrete event although

an individual’s needs may advance to those associated with depen-dence, co-morbidity and withdrawal management and support. Most services provided to the intoxicated drug user will be found outside specialist drug or mental health services (e.g. accident and emergency departments, police custody). All services, which have contact with opiate users, should have prompt access to the inject-able opiate antagonist naloxone which may be administered intra-venously, intramuscularly or subcutaneously and can be life-saving in the event of an opiate overdose. There is now widespread recognition of the problem of drug dependence among the prison population and evidence from database linkage studies showing that newly released prisoners are at substantial risk of fatal over-dose. In a study of 48 771 male and female sentenced prisoners in England and Wales released during 1998–2000, there were 442 recorded deaths (59 per cent drug-related) in year following release. There were 342 observed male

male and female sentenced prisoners in England and Wales released during 1998–2000, there were 442 recorded deaths (59 per cent drug-related) in year following release. There were 342 observed male deaths (45.8 expected in the general population) and 100 observed female deaths (8.3 expected). Drug-related male deaths were relatively more likely to involve heroin and female deaths were relatively more likely to involve benzodiaz-epines, cocaine and tricyclic antidepressants.

(d) Dependent drug users
This group comprise individuals who have drug-related problems and meet ICD/DSM dependence criteria. Dependence ranges in severity and is characterized by substantial impairment in the ability to control the frequency and amount used and various neuro-adaptational aspects. The majority of people presenting to specialist drug misuse services are in this group. They will require carefully planned community (and often residential treatment) together with the offer of aftercare support and access to social inclusion services to assist problems with housing, employment and training.
(e) Drug users with psychiatric co-morbidity

There is widespread concern about improving services and out-comes for people who have co-morbid psychiatric and substance use disorders. There is currently no research and clinical evidence-base for the effective management and care of patients in psychiatric inpatient units with psychoactive substance misuse co-morbidity and this is an important development area. There is some evidence that people with substance use problems and co-morbid psychiat-ric disorders appear to have a relatively high contact with medical services and may require more intensive treatment. However, it would appear that substance use disorders amongst people admitted for psychiatric treatment are of a less severe nature than those entering treatment for primary substance use problems. It is also important to consider and plan for the possibility that people with drug misuse and severe mental illness will not respond well or

comply with traditional care plans and arrangements. In terms of 
client attributes, the presence of psychiatric co-morbidity in drug users entering treatment has been linked to poorer outcomes.Pre-treatment psychiatric severity has been found to be predictive of outcome and this should be taken into account when selecting appropriate treatments. The importance of providing social 
inclusion and reintegration services, particularly in the ﬁ  rst three 
months of treatment has been advocated for community-based treatment services. However, the intensity or comprehensiveness of services per se  is not consistently associated with improved out-
come. The matrix of client attributes and treatment factors and processes has important implications for referral, assessment and client treatment-placement activities.
(f) Drug users in recovery

This group denotes individuals who have achieved a state of absti-nence from their main problem drug (or all drugs), usually through successful completion of a health care treatment episode. This group may require residential rehabilitation services or community based aftercare programmes and other supports.
The process and techniques of needs assessment

Service commissioners should follow a sequence of steps to inform the needs assessment for their population requirements. The over-arching goal is to produce a strategic commissioning framework which can be agreed across the health, social, and criminal justice partners. This remains an evolving area with guidance available from the NTA to assist the commissioning and implementation of work in this area. The usual steps when conducting a needs assess-ment are as follows:
X Allocation of resources and establishment of an agreed plan/
methods.
X Prevalence estimation of target population and identiﬁ  cation 
and proﬁ  ling of sub-groups.
X Mapping of treatment services provided in the locality and an

methods.
X Mapping of treatment services provided in the locality and an 
audit of treatment commissioning purchasing from services located outside the geographical boundary of the drug misuse partnership (e.g. Social Services purchasing of residential rehabilitation) to determine the extent to which demand is being met elsewhere.
X Audit of the demand proﬁ  le of treatment services (capacity; 
number of episodes; estimated number in need).
X Personal interviews with key informants across commissioning, 
provision and advocacy sectors.
X Focus group discussions with key stakeholders (commissioners, 
clinicians, treatment providers, service users, carers of service users) to explore what they want from services.
X A ‘gaps’ analysis of current and desired profile of service

X A ‘gaps’ analysis of current and desired profile of service 
provision (often qualitative exercise involving estimation of desired range of services to increase coverage for speciﬁ  c special 
groups).
X Recommendations for increasing treatment coverage, purchas-
ing efficiency, and service effectiveness based on available evidence.
X Assessment of reactions to recommendations from strategists, 
commissioners, purchasers, services providers, and service users.
X Development of an implementation plan based on the identiﬁ  -
cation of activities, resources, and timetables.
People in the seven sub-groups summarized above are not all the 
same and it is necessary to characterize each group on the basis of

519
the severity of their problems (and extent of any complications). 
It is important to note that the above sub-categories are not mutu-ally exclusive. Indeed, it is likely that an individual patient will occupy more than one category at any particular point in time (e.g. the injecting dependent heroin user with co-morbidity of HBV infec-tion). The multiple occupation of different categories may also vary over time. In addition to these six primary groups, there is a further category which can be labelled ‘at risk’ . There is particular concern about segments of the younger population (see below) thought to be at risk; prevention initiatives and general educational pro-grammes are Drug misuse services and treatment modalities.
The appraisal of the healthcare needs of the target populations 
and commissioning of strategic service responses should be ﬂ  exible

and commissioning of strategic service responses should be ﬂ  exible 
and adaptive to changing circumstances in each locality, including: variations and new trends in drugs use and consumption patterns; the geographical distribution and concentration of drug use; variations in demand for services; the changing relationship between drug use and other conditions (notably HIV infection, and blood borne viral hepatitis); changes in the organization of health services and monitoring the evidence-base for current and new treatment services.
Needs assessment activities are potentially costly activities. 
Intensive surveys of the resident population in most areas will be time consuming and expensive. It is quite likely that most partner-ships will employ alternative (and less precise) estimation methods with which to inform the direction and success of commissioning strategies. A qualitative approach to needs assessment can be

undertaken relatively quickly and can answer important questions 
concerning what commissioners, purchasers, service providers and service users want from treatment services and supports. Service user satisfaction surveys may be a useful means of gathering infor-mation about the extent to which a programme is perceived to have met an individual’s treatment wants and needs. A range of issues has been examined including the accessibility, adequacy, content, and impact of services received. In addition to serving a simple monitoring function for treatment service providers and their commissioners, treatment satisfaction is argued to be a valuable indicator of treatment experience. Treatment satisfaction can act as a moderator of treatment outcome, since it is reasonable to assume that less satisﬁ  ed clients may leave treatment prematurely or have

different responses to interventions. Both users and carers should be routinely involved and consulted on service development and the setting of commissioning activities. Many DAT Partnerships (and the services they commission) now have good user/carer involvement mechanisms and guidance exists to enable the devel-opment of these mechanisms where they are still lacking.
Monitoring the impact of interventions
Drug interventions are from identical in their structure and operation, and outcome studies show that their level of effective-ness varies widely. Many service providers have been interested in monitoring their own outcomes reﬂ  ecting organizational learning 
and quality values. The National Treatment Agency has now fur-ther developed the NDTMS as a national outcomes monitoring system. There are several beneﬁ  ts from collecting assessment and 
outcome information. Firstly, many patients perceive that a struc-tured approach to assessment and recording outcome is a reﬂ  ec-

tion of a service that is committed to providing the best care.The feedback of information describing during-treatment 
changes to the patient (and his/her spouse/partner or carers) by clinical staff can be a powerful motivational inﬂ  uence to reinforce 
progress and assist in personal treatment goal setting. Secondly, clinical staff can monitor the characteristics and outcomes of their caseloads and identify areas of priority work. Thirdly, service man-agers can aggregate information across staff as an indicator of how well the agency is serving its patients. Fourthly, information on samples of cases of aggregate summaries across services can be pro-vided to funding bodies and other government agencies to show 
the overall impact of treatment provision for a particular area.
In 2007, the NTA launched a national outcome monitoring

In 2007, the NTA launched a national outcome monitoring 
system for substance misuse treatment services. A brief, outcome monitoring instrument—the Treatment Outcomes Proﬁ  le (TOP) 
has been validated for this purpose. The TOP contains 30 items in four domains and is shown in Table 4.2.4.1. From these, a subset of 20 items are compiled at a national level to assess the overall effectiveness of the treatment system.
Case mix and performance analysis
Prognostic models of treatment outcome have been developed in our health care arenas with some success but the approach is in its infancy in the substance use disorders ﬁ  eld. Essentially, a set of 
variables which predict a health or other outcome are identiﬁ  ed 
using a statistical technique. Various methods can then be used to rank individual treatment provider’s outcome performance can then be ranked against this averaged outcome. Having adjusted for

using a statistical technique. Various methods can then be used to rank individual treatment provider’s outcome performance can then be ranked against this averaged outcome. Having adjusted for 
Table 4.2.4.1  The Treatment Outcomes Proﬁ  le (TOP)
Domain/section Item—in past 28 days
Substance use Number of days used the following substances
alcohol; opiates; cocaine; crack cocaine; amphetamines; 
cannabis; other (named)
Typical quantity consumed on typical day (recorded as 
units, grams or amount spent)
Number of days injected drugs in past 28 daysWhether shared needles and syringes (direct receptive 
sharing); Yes/No
Whether injected using a spoon, water or ﬁ  lter used by 
someone else (indirect receptive sharing; yes/no)
Crime Days committed shop theft; days sold drugs
Whether committed theft from or of vehicle (yes/no)Whether committed other property theft (yes/no)Whether committed fraud, forgery handling stolen goods 
(yes/no)
Whether committed assault or violence (yes/no)

(yes/no)
Health and social 
functioningHad acute housing need (yes/no)
Was at risk of eviction (yes/no)
Number of days had paid work in past 28 daysNumber of days attended college or school in past
28 days
Subjective rating of physical health (0 [poor] to 20 [good])Subjective rating of psychological health (0 [poor] to 
20 [good])
Subjective rating of quality of life (0 [poor] to 20 [good])4.2.4 assessing need and organizing services for drug misuse problems

SECTION 4  clinical syndromes of adult psychiatry 520
patient case mix differences, the objective is then to isolate the 
characteristics of very successful service providers as well as the correlates of less successful delivery of care. The results of this processcan then be used to guide the development of the local treatment system.
For information on the UK drug misuse strategy and national treatment 
system in UK see the following websites: http://drugs.homeofﬁ  ce.gov.
uk/ http://www.nta.nhs.uk/
 1. Audit Commission (2004). Drug Misuse 2004: Reducing the Local 
Impact.  London:Audit Commission.
 2. NTA and Department of Health (2005). Statistics From the National 
Drug Treatment Monitoring System  (NDTMS), 1 April 2003, 31 March 
2004. London: DH.
 3.. Hay, G., Gannon, M., MacDougall, J., et al. (2006). Local and national

 3.. Hay, G., Gannon, M., MacDougall, J., et al. (2006). Local and national 
estimates of the prevalence of opiate use and/or crack cocaine use (2004/05). In: Measuring Different Aspects of Problem Drug Use:
Methodological Developments  (eds. N. Singleton, R. Murray & 
L. Tinsley). London: Home Ofﬁ  ce. http://www.homeofﬁ  ce.gov.uk/rds/
pdfs06/rdsolr1606.pdf.
 4. National Treatment Agency (2002). Models of Care for Treatment of 
Adult Drug Misusers . NTA, London.
 5. National Treatment Agency (2006). Models of Care for Treatment of 
Adult Drug Misusers:  update 2006.London: NTA.
 6. Higgins, S. T., Delaney, D. D., Budney, A. J., et al. (1991). A behavioral 
approach to achieving initial cocaine abstinence. American Journal of 
Psychiatry ,148, 1218–24.
 7. Silverman, K., Chutuape, M. A., Bigelow, G. E. et al. (1999).

 7. Silverman, K., Chutuape, M. A., Bigelow, G. E. et al. (1999). 
Voucher-based reinforcement of cocaine abstinence in treatment-resistant methadone patients: effects of reinforcement magnitude. Psychopharmacologia ,146, 128–38.
 8. National Institute for Health and Clinical Excellence (2007). Drug 
misuse: psychosocial interventions.NICE guideline (http://guidance.nice.org.uk/CG51). Accessed on 27.07.07.
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misuse: opioid detoxiﬁ  cation. NICE guideline (http://guidance.nice.
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2005. HPA, London.

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in Sydney, Australia: II. Responses to overdose. Addiction ,
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4.3
Schizophrenia and acute 
transient psychotic disorders
4.3.1 Schizophrenia: a 
conceptual history
We know that psychotic disorders have been present and publicly 
recognized at least since classical times because of their portrayals in literature: the madness of Medea, the frenzied behaviour in The Bacchae , or the paranoia of Othello. Perhaps the most ‘valid’ 
portrayal from a modern clinical perspective is the feigned madness of ‘Poor T om’ in King Lear. Poor T om is a ‘bedlam beggar’ who encounters Lear during the great scenes of madness, portrayed while the world itself is also in the midst of a terrible storm. T om’s speech is a classical example of schizophrenic thought disorder, but he also experiences delusions and visual hallucinations:
Who gives anything to poor T om? Whom the foul ﬁ  end hath led 
through ﬁ  re and through ﬂ  ame, and through ford and whirlpool, o’er

through ﬁ  re and through ﬂ  ame, and through ford and whirlpool, o’er 
bog and quagmire, that hast laid knives under his pillow, and halters in his pew; set ratsbane by his porridge; made him proud of heart, to ride on a bay trotting-horse over four-inch’d bridges, to course his own shadow for a traitor. Bless thy ﬁ  ve wits! T om’s a-cold, –O, do 
de, do de, do de. Bless thee from whirlwinds, star-blasting, and taking! Do poor T om some charity, whom the foul ﬁ  end vexes. There could 
I have him now, –and there, –and there again, and there. ( King Lear ,
III. iv. 51–60)
However, the deﬁ  nition and delineation of schizophrenia as a 
discrete disorder is a relatively recent phenomenon.
The founding fathers of the concept: 
Kraepelin and Bleuler
The earliest academic formulations of the concept of schizophrenia 
occurred in the mid-nineteenth century in the work of Bénédict-Auguste Morel and Karl Kahlbaum.

(1) Morel coined the term 
‘démence precoce’ to refer to a disorder that he observed in young people that was characterized by cognitive impairments and progressive degeneration. He did not develop the concept fully, however. Instead, under the inﬂ  uence of Darwinian thinking,
he became preoccupied with the general concept of hereditary Contents
 4.3.1 Schizophrenia: a conceptual history
 4.3.2 Descriptive clinical features of schizophrenia
 4.3.3 The clinical neuropsychology of
 4.3.4 Diagnosis, classiﬁ  cation, and differential diagnosis of schizophrenia
 4.3.5 Epidemiology of schizophrenia
 4.3.6 Aetiology
factors for schizophrenia

 4.3.6.2 The neurobiology of schizophrenia
and their prediction
 4.3.8 Treatment and management of schizophrenia
 4.3.9 Schizoaffective and schizotypal disorders
 4.3.10 Acute and transient psychotic disorders

SECTION 4  clinical syndromes of adult psychiatry 522
degeneration, which he described in disorders ranging from intel-
lectual disability to alcoholism. This general concept was highly inﬂ uential throughout the nineteenth and early twentieth century, 
which led to some of the earliest studies of the familiality of mental illnesses, and laid early foundations for later efforts to examine the role of genetic factors in schizophrenia. Kahlbaum’s seminal contribution was an emphasis on using course of illness (as opposed to symptoms) to deﬁ  ne discrete disorders. He objected to the 
concept that there was only one form of severe mental illness (‘unitary psychosis’ or ‘einheitspsychose’) and argued that various kinds of psychotic disorders could be differentiated from one another based on changing patterns of symptoms and long-term outcome. Kahlbaum identiﬁ  ed one type as ‘hebephrenia’ .
Our modern concept of schizophrenia primarily derives, how-

ever, from the interaction between two great clinicians early in the twentieth century: Emil Kraepelin and Eugen Bleuler.
Although his ideas were presaged by Morel and Kahlbaum, Emil 
Kraepelin was clearly the ﬁ  rst to give a detailed description of this 
syndrome and a compelling justification for its delineation. Kraepelin highlighted his concept of the key features of thedisorder in the name that he chose for it: It was an illness thattended to begin at an early age (‘praecox’) and to have a relatively 
chronic course characterized by signiﬁ  cant cognitive and social

chronic course characterized by signiﬁ  cant cognitive and social 
impairment (‘dementia’). Alois Alzheimer was a member of Kraepelin’s department in Munich and used the tools of neuropa-thology to study a similar dementia that began at a later age; exam-ination of the brains of these individuals at post-mortem revealed a characteristic neural signature—plaques and tangles. Kraepelin began to call this disorder Alzheimer’s disease and thus gave itits current name, as well as its differentiation from dementiapraecox. A similar neuropathological signature was sought for dementia praecox, but it was never found, although Kraepelin hypothesized that it must be a disease involving prefrontal and temporal regions
(2):

(2):
If it should be demonstrated that the disease attacks by preference the frontal areas of the brain, the central convolutions and the temporal lobes, this distribution would in a certain measure agree with our present views about the site of the psychic mechanisms which are principally injured by the disease. (p. 219)
Kraepelin did not select any speciﬁ  c clinical feature as patho-
gnomic, but he did stress the importance of several symptoms as characteristic:
. . . there are apparently two principal groups of disorders which characterise the malady. On the one hand we observe a weakening
of those emotional activities which permanently form the mainsprings of volition . In connection with this, mental activity and instinct for 
occupation become mute. The result of this part of the morbidprocess is emotional dullness, failure of mental activities, loss ofmastery over volition, of endeavor, and of ability for independent action.

The second group of disorders . . . consists in the loss of the inner unity
of the activities of intellect, emotion, and volition in themselves and among one another … the near connection between thinking and 
feeling, between deliberation and emotional activity on the one hand, and practical work on the other is more or less lost. Emotions do 
not correspond to ideas. The patients laugh and weep without recog-
nizable cause, without any relation to their circumstances and their experiences, smile while they narrate the tale of their attempts at suicide . . . (pp. 74–5).Thus, for Kraepelin, what we now refer to as negative sym-
ptoms and fragmenting of thought were two key features of the disorder.
Bleuler was a near contemporary of Kraepelin. During their

two long careers they maintained a dialogue between their native countries of Germany and Switzerland. Kraepelin was a thorough-going empiricist with a keen eye for detail, while Bleuler was primarily a high-level conceptualizer, although he clearly also had vast clinical experience. Bleuler chose to highlight fragmenting of thinking as the most fundamental feature of schizophrenia and designated it as the pathognomonic symptom. That is, he explicitly stated that this particular symptom (‘loosening of associations’) was present in all patients with schizophrenia and did not occur in other disorders. Because of the importance that he gave to this par-ticular symptom, he renamed the illness after it (schizophrenia = fragmenting of mind). T o this symptom, he added several others that he also considered to be of high importance. These included loss of volition, impairment in attention, ambivalence, autism, and affective blunting. He regarded these symptoms as basic or funda-mental and

considered to be of high importance. These included loss of volition, impairment in attention, ambivalence, autism, and affective blunting. He regarded these symptoms as basic or funda-mental and the other symptoms observed in the disorder, such as delusions or hallucinations, as secondary or accessory. He pointed out that these accessory symptoms tended to occur in a variety of

other conditions, such as manic-depressive illness, delirium, or 
dementia.
Certain symptoms of schizophrenia are present in every case and in every period of the illness even though, as with every other disease symptom, they must have attained a certain degree of intensity before they can be recognized with any certainty . . . Besides the specific permanent or fundamental symptoms, we can find a host of other, more accessory manifestations such as delusions, hallucinations, or catatonic symptoms . . . As far as we know, the fundamental symptoms are characteristic of schizophrenia, while the accessory symptoms may also appear in other types of illness (p. 13).
Bleuler’s conceptualization of the disorder captured the imagi-

nation of clinicians and investigators throughout the world, and the name he chose for the disorder eventually became the one that is now universally used. The prophecy of Kraepelin’s tomb-stone came true: ‘though his name will be forgotten, his work will live on’ . During the much of the twentieth century, Bleuler’s conceptualization and terminology prevailed. Although he drew on Kraepelinian concepts, very few people were aware of the magnitude of Kraepelin’s contributions. Students of schizophrenia used Bleuler’s name for the disorder and deﬁ  ned it in terms of 
‘the four A ’s’ (associations, autism, affect, and ambivalence).
Schneiderian symptoms, psychosis, and the 
dominance of diagnostic criteria
The Bleulerian emphasis slowly began to change, however, begin-

ning in the late 1960s and 1970s. This change in emphasis arose primarily from an interest in improving diagnostic precision and reliability. Because they are essentially ‘all or none’ phenomena, which are relatively easy to recognize and deﬁ  ne, ﬂ  orid psychotic 
symptoms such as delusions and hallucinations were steadily given greater prominence and indeed even placed at the forefront of the deﬁ  nition of schizophrenia. Bleuler’s secondary or accessory 
symptoms began to be treated as the pathognomonic symptoms.
The emphasis on ﬂ  orid psychotic symptoms arose because of the 
inﬂ uence of Kurt Schneider and the interpretation of his thinking

523
by inﬂ  uential British psychiatrists. Schneider was greatly inﬂ  uenced 
by the work of Karl Jaspers, who explored phenomenology and created a bridge between psychiatry and philosophy. Jaspers believed that the essence of psychosis was the experience of phenomena that were ‘nonunderstandable’—i.e. symptoms that a ‘normal’ person could not readily imagine experiencing. Schneider, like Bleuler, wished to identify symptoms that were fundamental. He concluded that one critical component was an inability to ﬁ  nd 
the boundaries between self and not-self and a loss of the sense of personal autonomy. This led him to discuss various ‘ﬁ  rst-rank’ 
symptoms that were characterized by this loss of autonomy, such as thought insertion or delusions of being controlled by outside forces.
(3–5)
Schneiderian ideas were introduced to the English-speaking 
world by British investigators and began to exert a powerful inﬂ  u-

(3–5)
ence on the concept of schizophrenia. An emphasis on Schneiderian ﬁ rst-rank symptoms satisﬁ  ed the fundamental need to ﬁ  nd an 
anchor in the perplexing ﬂ  ux of the phenomenology of schizo-
phrenia. Schneiderian symptoms were incorporated into the ﬁ  rst 
major structured interview developed for use in the International Pilot Study of Schizophrenia, the Present State Examination (PSE).
(6) From this major base, they were thereafter introduced 
into other standard diagnostic instruments such as the Schedule for Affective Disorders and Schizophrenia (SADS),
(7) Research 
Diagnostic Criteria (RDC),(8) and the Diagnostic and Statistical 
Manual  (DSM-III ).(9)
The emphasis on positive symptoms, and especially Schneiderian 
symptoms, derived from several concerns. The first was that Bleulerian symptoms were difﬁ  cult to deﬁ  ne and rate reliably.

symptoms, derived from several concerns. The first was that Bleulerian symptoms were difﬁ  cult to deﬁ  ne and rate reliably. 
They are often continuous with normality, while positive psychotic symptoms were clearly abnormal. In addition to concerns about reliability, work with the IPSS and the US/UK study also had indicated that in the United States the concept of schizophrenia had broadened to an excessive degree, particularly in the Northeastern parts of the United States. Thus, in the United States, there was clearly a need to narrow the concept of schizophrenia. Stressing ﬂ  orid psychotic symptoms, particularly Schneiderian 
symptoms, was a useful way to achieve this end, since it appeared that schizophrenia was often being diagnosed on the basis of mild Bleulerian symptoms. When diagnostic criteria such as the 
RDC and later DSM-III  were written, these placed a substantial

RDC and later DSM-III  were written, these placed a substantial 
emphasis on positive symptoms and minimized negative symptoms.
While there have been many good consequences of this progres-
sion and of the interest in Schneider’s work, there have also been problems.
From a Schneiderian perspective, Schneider’s work and point of 
view has been oversimplified and even misunderstood. As a Jasperian phenomenologist, Schneider was in fact deeply interested in the subjective experience of schizophrenia—in understanding the internal psychological processes that troubled his patients. For him, the fundamental core of the illness was not the speciﬁ  c 
ﬁ rst-rank symptoms themselves, but rather the internal cognitive 
and emotional state that they reﬂ  ected. It is somewhat ironic 
that he has become the symbol of objective quantiﬁ  cation and 
reductionism. He himself was a complex thinker who was con-cerned about individual patients.

The development of diagnostic criteria for schizophrenia has 
also had both advantages and disadvantages. When DSM-III  was originally developed, it was intended only as a ‘provisional consen-
sus agreement’ based on clinical judgement. The criteria were created by a small group of individuals who reached a decision about what to include based on a mixture of clinical experience and research data available up to that point. The criteria were chosen to serve as a gatekeeper that would include or exclude indi-vidual cases, and they were not intended to be a full description of the illness. Unfortunately, they are now sometimes treated as a textbook of psychiatry. Further, the criteria have become reiﬁ  ed 
and given a power that they originally were never intended to 
have.

have.
Diagnostic criteria have substantial and undeniable advantages, 
they improve reliability, provide a basis for cross-centre stand-ardization both nationally and internationally, improve clinical communication, and facilitate research. However, they may also have potential disadvantages and even abuses: they provide an oversimpliﬁ  ed and incomplete view of the clinical picture, discour-
age clinical sensitivity to individual patients and comprehensive history-taking, lead students and even clinicians to believe that ‘knowing the criteria is enough’ , reify an agreement that was only intended to be provisional, and discourage creative or innovative thinking about the psychological and neural mechanisms of schizophrenia.
The concept of positive and 
negative symptoms
Neither Kraepelin nor Bleuler actually used the terms ‘positive

Neither Kraepelin nor Bleuler actually used the terms ‘positive 
symptoms’ or ‘negative symptoms’ , although the concepts are embedded in their writings. While various sources for this term can be cited,
(10) one of the earliest and most prominent was Hughlings-
Jackson.(11) Although Jackson’s work was not published until much 
later, in the late nineteenth century Jackson speculated about the mechanisms that might underlie psychotic symptoms:
Disease is said to ‘cause’ the symptoms of insanity. I submit that dis-ease only produces negative mental symptoms, answering to the dissolution, and that all elaborate positive mental symptoms (illu-sions, hallucinations, delusions, and extravagant conduct) are the out-come of activity of nervous elements untouched by any pathological process; that they arise during activity on the lower level of evolution remaining.
Thus Jackson believed that some symptoms represented a

Thus Jackson believed that some symptoms represented a 
relatively pure loss of function (negative symptoms answer to the dissolution), while positive symptoms such as delusions and hallucinations represented an exaggeration of normal function and might represent release phenomena. Jackson presented these ideas at a time when Darwinian evolutionary theories were achiev-ing ascendance, and his concepts concerning the mechanisms that produced the various symptoms were clearly shaped by a Darwinian view that the brain is organized in hierarchical evolutionary layers. Positive symptoms represent aberrations in a primitive (perhaps limbic) substrate that is for some reason no longer monitoredby higher cortical functions. Thus Jackson’s concept of negative versus positive symptoms rather closely resembles thosewhich are currently discussed. Although today most investigators 
do not necessarily embrace the specific mechanism that he

proposed, they accept his view that they must be understood in terms of brain mechanisms, as well as his basic descriptivepsychopathology.4.3.1 schizophrenia: a conceptual history

SECTION 4  clinical syndromes of adult psychiatry 524
References to positive and negative symptoms occurred sporadi-
cally during the 1970s, sometimes making clear references to Jackson’s ideas and sometimes simply presenting notions about the clinical meaning of the distinction. Notable examples include the descriptions of Fish,
(3) a reference to the terms by Strauss 
and others,(12) and Iowa work on affective blunting and on thought 
disorder, classifying it as positive versus negative.(13, 14)
In 1980, Crow published an inﬂ  uential paper describing a two 
syndrome hypothesis of schizophrenia using the terms ‘positive’ and ‘negative’ symptoms.
(15) He proposed that schizophrenia could

(15) He proposed that schizophrenia could 
be divided into two different syndromes, which he referred to as Type I and Type II. Type I schizophrenia was characterized by prominent positive symptoms, an acute onset, good premorbid adjustment, a good response to treatment, intact cognition, intact brain structure, and an underlying mechanism that was neuro-chemical (dopaminergic) and therefore reversible. Type II schizo-phrenia was characterized by prominent negative symptoms, an insidious onset, poor premorbid adjustment, a poor response to treatment, impaired cognition, structural brain abnormalities (i.e. ventricular enlargement as visualized by Computerized T omography [CT]), and an underlying mechanism that was char-acterized by neuronal loss and therefore irreversible. This proposal was highly generative for research in schizophrenia during the 1980s, primarily because it combined speculations about clinical 
presentation and about underlying neural mechanisms within a

presentation and about underlying neural mechanisms within a 
single hypothesis.
Two major problems were inherent in Crow’s presentation 
of this hypothesis, however, which initially limited its empirical testing. One problem was its failure to specify a clear method for measuring positive and negative symptoms, and the second was its failure to indicate which of the broad array of variables associated with each of the two syndromes should be considered dependent or independent. Which symptoms of schizophrenia should be considered to be positive and which negative? Which variable—or group of variables—should be used to define the separate syndromes and test whether the hypothesized relationships were present?
Solutions to these problems were proposed by the investigative 
team at the University of Iowa.
(16) Reliable methods for deﬁ  ning

(16) Reliable methods for deﬁ  ning 
and differentiating positive and negative thought disorder and other negative symptoms such as affective blunting had already been developed at Iowa
(13, 14)  and the research group there also had 
a long tradition of developing diagnostic criteria. Consequently, we developed structured scales for the assessment of both positive and negative symptoms, the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS).
(16–18)  These scales were intended 
to provide a more comprehensive, reliable, and well-anchored set of measurements for the evaluation of psychopathology in schizo-phrenia than had been provided by standard instruments such as the Brief Psychiatric Rating Scale (BPRS).
(19) They were subjected

(19) They were subjected 
to rigorous assessment of their psychometric properties, including internal consistency, reliability, and validity. They were quickly translated into a variety of languages and widely used throughout the world.
In addition, a solution to the second problem was imple mented 
by using a standard strategy in the study of psychopathology: the core clinical syndrome would be treated as the independentvariable, while the various associated features would be(somewhat arbitrarily) designated as dependent. T o this end, crite-
ria were developed that could be used to classify schizophrenic patients as positive, negative, or mixed. Initial work with thesecriteria suggested that this strategy could be quite useful.
(16, 17)

(16, 17)
As Crow hypothesized, negative patients differed from positive patients in the predicted direction: larger ventricular brain ratio (VBR), poorer premorbid adjustment, lower educational achieve-ment, and poorer cognitive performance. Many subsequent studies continued to explore the two syndrome hypothesis, with themajority conﬁ  rming at least some aspects of it. However, other 
problems with this hypothesis also became evident. Perhaps the most vexing for the hypothesis, and for the application of criteria to categorize patients based on clinical presentation, was the large number of patients with a mixture of positive and negative symp-toms. The hypothesis had difﬁ  culty in explaining how patients who

were both positive and negative could have both reversible and irreversible abnormalities, good and poor premorbid adjustment, and other counterintuitive and contradictory ﬁ  ndings. For these 
reasons, most investigators have regretfully abandoned this
appealingly simple and heuristic hypothesis during recent years.
However, the clinical distinction between positive and negative 
symptoms has remained relatively robust. The tendency to distin-guish between these two classes of symptoms has become wide-spread, and the terms have passed into standard clinical usage. The alacrity with which the terms have been adopted suggests that they ﬁ ll a useful linguistic and conceptual niche. Negative symptoms

are an important component of schizophrenia, and the use of the ‘positive’ and ‘negative’ terminology gives them recognition and even equal weight. As the Bleulerian symptoms received de-emphasis because of concerns about reliability, they left a void in the descriptive lexicon. Patients were designated as having ‘recovered’ when their delusions and hallucinations were no longer present or prominent; yet many remained unemployed, unable to return to school, or socially isolated. What might explain this outcome if their symptoms were genuinely absent? Upon reﬂ  ec-
tion, it became evident that only some of their symptoms were absent, and that a group of ‘no name’ symptoms were the likely explanation. If these symptoms could be named ‘negative’ , grouped together, measured objectively and reliably, and related to outcome and treatment, an important mechanism for clinical description and communication was restored. Although the oversimpliﬁ  ed

distinction between positive and negative implied in the two syndrome hypothesis might be misleading, it was useful to recog-nize that some symptoms tend to get patients hospitalized and to call these ‘positive’ and that other symptoms tend to lead to psychosocial morbidity and to call these ‘negative’ . Thus the 
distinction at the level of symptoms (as opposed to syndromes or 
disease categories) is helpful descriptively.
The distinction has also persisted because standardized and

The distinction has also persisted because standardized and 
reliable methods have been developed for assessing these symp-toms and placing them in broad general classes. Instruments such as the SANS and SAPS have facilitated the persistence of the terminology because they have provided the tools for rating and measuring. Although tools were at hand for most positive symp-toms, no scale was available at all for negative symptoms priorto the SANS. The extensive and repeated documentation ofits reliability has quieted concerns that negative symptoms aretoo ‘soft’ to be assessed precisely, accurately, and objectively. Furthermore, other simpler scales, targeted primarily for use in

525
clinical drug trials, have also been developed.(20) By the time that 
DSM-IV(21) and ICD-10(22) were written, the concept of positive 
and negative symptoms was so widely accepted that negative symp-toms were included in their diagnostic criteria for the ﬁ  rst time.
Beyond diagnostic criteria and the search 
for fundamental mechanisms
As the present moves towards the future, corrective readjustments 
are continuing to occur. Paradoxically, these often occur by return-ing to the past and coming back full circle to the work of Kraepelin, Bleuler, Jackson, and Schneider.
Clinically, the emphasis on negative as well as psychotic symp-

toms is leading to increased interest in the full range of symptoms of schizophrenia and in developing methods for treating that full range. In particular, there has been a growing interest in developing improved treatments for negative symptoms. The interest in nega-tive symptoms has been complemented by a return to an interest in cognitive aspects of schizophrenia. Many negative symptoms are cognitive in nature—alogia (poverty of thought and speech), avolition (inability to formulate plans and pursue them), and attentional impairment. While their assessment may emphasize objective aspects of behaviour in order to achieve reliability, their 
underlying essence is in the domains of thought and emotion. 
Increasingly, therefore, investigators are returning to the original insights of Kraepelin and Bleuler that the core symptoms of schizophrenia represent a fundamental deﬁ  cit in cognition and 
emotion.

emotion.
Several prominent investigators have turned from a focus on 
explaining and ‘localizing’ the speciﬁ  c symptoms of schizophrenia 
to a search for more fundamental underlying cognitive mechanisms.
(23) Examples include Frith’s hypotheses concerning 
an inability to think in ‘metarepresentations’ ,(24) Goldman-Rakic’s 
studies of working memory,(25) our descriptions of cognitive 
dysmetria Andreasen,(26) or the work of Holzman,(27) Braff,(28)
Swerdlow and Geyer,(29) and Freedman(30) on information pro-
cessing and attention. These cognitive models provide a general theory of the disease that is consistent with its diversity of symp-toms, permit testing in human beings with a variety of convergent techniques (e.g. imaging, neurophysiology), and even permit modelling in animals. This efﬁ  cient and parsimonious approach 
offers consider hope for the future because it facilitates the search both for improved treatments and for molecular mechanisms.

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the role of dopamine. The British Journal of Psychiatry ,137, 383–6.
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21. American Psychiatric Association. (1994). Diagnostic and statistical

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disorders (including disorders of psychological development): diagnosis criteria for research. International classiﬁ  cation of diseases, 
tenth edition (ICD-10). Geneva.
23. Andreasen, N.C. (1997). Linking mind and brain in the study of mental 
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1586–93.
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in schizophrenia. The Journal of Neuropsychiatry and Clinical 
Neuroscience ,6(4), 348–57.

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27. Holzman, P .S., Levy, D.L., and Proctor, L.R. (1976). Smooth pursuit 
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SECTION 4  clinical syndromes of adult psychiatry 526
29. Swerdlow, N.R. and Geyer, M.A. (1993). Clozapine and haloperidol 
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neuronal dysfunctions in schizophrenia. Schizophrenia Research ,4(2), 
233–43.
4.3.2. Descriptive clinical 
features of schizophrenia
The clinical features of schizophrenia embrace a diverse range of 
disturbances of perception, thought, emotion, motivation, and motor activity. It is an illness in which episodes of ﬂ  orid distur-
bance are usually set against a background of sustained disability. The level of chronic disability ranges from a mild decrease in the ability to cope with stress, to a profound difﬁ  culty in initiating and 
organizing activity that can render patients unable to care for themselves.
Disorders of thought and perception

Delusions
Although there are no features that provide an unambiguousdistinction between the delusions of schizophrenia and thoseof other psychotic illnesses, the delusions most typical ofschizophrenia have an enigmatic character rarely seen in otherdisorders. In contrast to the delusions of affective psychosis,which usually have content consistent with the prevailing emotion-al state, in schizophrenia delusions often appear to reflect afragmented experience of reality. This fragmentation is manifest in several ways.
X There is a lack of logical consistency between the components 
of the belief, or between the belief and common understanding of what is possible. For example, a patient was very distressed by the belief that he had no head and also that there was blood all over his face.
X Behaviour bears an unpredictable relationship to the delusional

X Behaviour bears an unpredictable relationship to the delusional 
belief. In some instances, the patient believes he has a specialrole or identity, yet for the most part, lives a life that is scarcely influenced by the belief. In the words of Bleuler
(1): ‘Kings, 
Emperors, Popes, and Redeemers engage for the most part, in quite banal work, provided they still have any energy at all for activity’ .
X In the chronic phase of the illness, patients might acknowledge 
that a former delusion was not justiﬁ  ed, yet in the same inter-
view they reiterate the delusional belief. Bleuler(1) reported: 
‘sometimes the patients even produce thoughts which are only understandable if it is assumed that the delusions still retain some reality for these patients even though consciously they may reject them’ .
The mental mechanism of schizophrenic delusions remains to be

The mental mechanism of schizophrenic delusions remains to be 
ascertained. It is not a lack of capacity for logical thought; rather it appears that certain ideas acquire an attribute that exempts them from the normal processes of validation. This phenomenon is 
illustrated by the historic case of Daniel Schreber,
(2) a high-ranking 
judge from Leipzig, who suffered a late-onset schizophrenic illness. After obtaining a court order for discharge from his second hospi-tal admission he published his memoirs
(3) in a volume that includes

(3) in a volume that includes 
his own account of his beliefs, and also the report prepared by the asylum director, Dr Weber, opposing his discharge. For the purpose of understanding the nature of delusions in schizophrenia, Schreber’s account is of special value because we have access to his own perceptions of his condition in addition to detailed accounts by his physician. Dr Weber reported that Schreber exhibited lively interest in his social environment, a well-informed mind, and sound judgement, while nonetheless maintaining his delusional beliefs in a manner that would accept no contrary argument. Schreber himself agreed that his beliefs were unchangeable. He believed that he had a mission to redeem the world and restore humankind to its lost state of bliss. His system of delusions included the belief that he was being transformed into a voluptuous female partner of God. He considered that his beliefs belonged to a domain

that was exempt from normal logic: ‘I could even say with Jesus 
Christ: My kingdom is not of this world; my so-called delusions are concerned solely with God and the beyond’ . Furthermore, he maintained total conviction in his core beliefs despite recogniz-ing that his experiences earlier in his illness had been unrealistic. He stated:
Having lived for months among miracles, I was inclined to take more or less everything I saw for a miracle. Accordingly, I did not know whether to take the streets of Leipzig through which I traveled as only theatre props, perhaps in the fashion in which Prince Potemkin is said to have put them up for Empress Catherine II of Russia during her travels through the desolate country, so as to give the impression of a ﬂ ourishing countryside.
Thus, in the stable phase of his illness, Schreber recognized that 
his earlier experiences were unrealistic and that his current beliefs deﬁ ed normal logic, but appeared to regard them as exempt from

his earlier experiences were unrealistic and that his current beliefs deﬁ ed normal logic, but appeared to regard them as exempt from 
the need for validation. The late onset of his illness and his high level of professional achievement are unusual for an individual with schizophrenia, and raise questions about the diagnosis. However, the fact that he eventually suffered a marked deterioration in function during his third episode of illness strongly supports the diagnosis of schizophrenia.
In many instances, the delusions of schizophrenia appear to arise 
from an altered experience of self. The phenomena identiﬁ  ed by 
the German psychiatrist, Kurt Schneider
(4) as ﬁ rst-rank symptoms 
of schizophrenia (discussed in greater detail below) include several symptoms that entail an aberrant experience of ownership of one’s own thought, will, action, emotion, or bodily function, which the patient attributes to alien inﬂ  uence. In some cases, delusions might

arise from a delusional mood, i.e. an altered sense of reality in which the current circumstances acquire an indeﬁ  nable transcen-
dental quality.
Although the delusions most characteristic of schizophrenia have 
an incongruous quality, it is not uncommon for schizophrenic patients to have coherent delusions that are internally consistent and produce predictable behavioural responses. In particular, coherent persecutory delusions are common, and can lead to defen-sive actions such barricading oneself in one’s room with blinds drawn. Ideas of reference and delusions of reference are also prevalent. For example, a patient might report that television

527
programmes refer speciﬁ  cally to him or her. In the International 
Pilot Study of Schizophrenia(5) conducted by the World Health 
Organization, ideas of reference were reported in 70 per cent of cases, suspiciousness in 66 per cent, and delusions of persecution in 64 per cent.
Hallucinations
Hallucinations in any modality can occur, but auditory hallucina-tions are the most prevalent in schizophrenia. Hearing voices speaking in the third person is the most speciﬁ  c. This experience is 
listed among the Schneiderian ﬁ  rst-rank symptoms. Sometimes 
the content is mundane, as in the instance when a patient of Bleuler
(1) heard a voice saying ‘Now she is combing her hair’ while 
she was grooming in the morning. In other instances there is an implied criticism, as in the case reported by Schneider
(4) of a 
woman who heard a voice saying ‘Now she is eating; here she is munching again’ , whenever she wanted to eat.
Second-person auditory hallucinations are also common. In the

(4) of a 
Second-person auditory hallucinations are also common. In the 
International Pilot Study of Schizophrenia,
(5) voices speaking to 
the patient were reported in 65 per cent of cases. Voices might issue commands that the patient obeys. In some instances, the patient engages in a dialogue with the voices.
During the acute phase of illness, auditory hallucinations
usually have the same sensory quality as voices arising fromsources in the external world. In some instances the voice isattributed to a radio-transmitter implanted in the body,especially in the teeth. In the chronic phase, the voices are often recognized as coming from within the person’s own mind. Kraepelin
(6) reports: ‘at other times they do not appear to the

(6) reports: ‘at other times they do not appear to the 
patient as sense perceptions at all; they are ‘voices of conscience’; ‘voices which do not speak with words’’ . These experiences are pseudohallucinations, but nonetheless they are a signiﬁ  cant feature 
in many cases.
In schizophrenia, visual hallucinations are less common than 
auditory hallucinations, but do occur. Somatic hallucinations are also relatively common, and often are associated with a delusional misinterpretation. For example, a young man reported sensations in his belly that he attributed to a snake, which he believed had crawled up his anus.
Schneiderian ﬁ  rst-rank symptoms
Kurt Schneider(4) identiﬁ  ed a set of phenomena that he considered 
were strongly indicative of schizophrenia in the absence of overt brain disease. These symptoms, listed in Table 4.3.2.1, have become 
known as ﬁ  rst-rank symptoms. Schneider did not consider that
the diagnosis could be made simply on the presence of one such

the diagnosis could be made simply on the presence of one such 
symptom; on the contrary, he warned,
(4) ‘a psychotic phenomenon 
is not like a defective stone in an otherwise perfect mosaic’ . Schneider did not define the phenomena precisely, and clinicians haveinterpreted his writings differently. Mellor
(7) formulated a precise 
set of deﬁ  nitions and found that, according to these strict criteria, 
72 per cent of patients with schizophrenia exhibited at least one ﬁ rst-rank symptom. Applying the same criteria, O’Grady
(8) found 
that in a series of cases assessed at admission to hospital,73 per cent of schizophrenic patients exhibited at least one ﬁ  rst-
rank symptom, while no cases of affective psychosis did. However, applying less strict criteria, O’Grady found more broadly deﬁ  ned 
ﬁ rst-rank symptoms in 14 per cent of patients with affective

ﬁ rst-rank symptoms in 14 per cent of patients with affective 
psychosis.Three of the ﬁ  rst-rank symptoms (voices commenting, voices 
discussing, and audible thoughts) involve auditory hallucinations, while the remainder entail delusional attributions to experiences or perceptions. Although Schneider himself avoided speculating on the theoretical implications of these phenomena, it is notable that most of them involve a disorder of the sense of ownership of one’s own mental or physical activity. Thought broadcast, thought with-drawal, and thought insertion reﬂ  ect the experience of loss of 
autonomy over thought, while made will, made acts, made affect, and somatic passivity reﬂ  ect loss of autonomy over action, will, 
affect, and bodily function.
Mellor
(7) emphasizes that there are two aspects to these phenom-

Mellor
ena: the experience of loss of autonomy and the delusional attribution to alien inﬂ  uence. As an illustration of made acts, 
Mellor reports a patient who reported that his ﬁ  ngers moved to 
pick up objects ‘but I don’t control them … I sit there watching 
them move, and they are quite independent, what they do is noth-ing to do with me. I am just a puppet … I am just a puppet who is 
manipulated by cosmic strings’ . T o illustrate made affect, Mellor quotes a young woman: ‘I cry, tears roll down my cheeks and I look unhappy, but inside I have a cold anger because they are using me in this way, and it is not me who is unhappy, but they are projecting unhappiness into my brain’ .
Delusional perception, in which an entirely unwarranted conclu-

sion is drawn from a normal perception, illustrates the incongruity between a delusional idea and concurrent mental activity, which is characteristic of schizophrenia. However, the way in which delusional perceptions often crystallize from a delusional mood indicates that it is not merely a matter of illogical inference; the delusional idea is more like a divine revelation. Mellor
(7) gives the 
example of an Irishman who experienced a sense of foreboding Table 4.3.2.1  Schneiderian ﬁ  rst-rank symptoms
Voices commenting—a hallucinatory voice commenting on one’s actions in 
 the third person
Voices discussing or arguing—hallucinations of two or more voices discussing 
 or arguing about oneself
Audible thought—hearing one’s thoughts aloudThought insertion—the insertion, by an alien sources, of thoughts that are 
 experienced as not being one’s own
Thought withdrawal—the withdrawal of thoughts from one’s mind by an

experienced as not being one’s own
Thought withdrawal—the withdrawal of thoughts from one’s mind by an 
 alien agency
Thought broadcast—the experience that one’s thoughts are broadcast so as 
 to be accessible to others
Made will—the experience of one’s will being controlled by an alien inﬂ  uenceMade acts—the experience that acts executed by one’s own body are the 
 actions of an alien agency, rather than oneself
Made affect—the experience of emotion that is not one’s own, attributed to 
 an alien inﬂ  uence
Somatic passivity—bodily function is controlled by an alien inﬂ  uenceDelusional perception—the attribution of a totally unwarranted meaning to a 
 normal perception4.3.2. descriptive clinical features of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 528
while seated at the breakfast table in a lodging house. When another 
lodger innocently pushed the salt cellar towards him, he suddenly knew this meant that he must return home to greet the Pope who was visiting his family to thank them because Our Lord was to be born again to one of the women.
Disorders of the form and ﬂ  ow of thought
The speech of schizophrenic patients is often difﬁ  cult to understand 
because of abnormalities of form of the underlying thought. However, the clinical assessment of thought form disorder remains a major challenge. This is due in part to the fact the essential features of formal thought disorder in schizophrenia have yet to be defined in a fully satisfactory manner. Furthermore, thought disorder is usually manifest during spontaneous speech, making it difﬁ cult to create circumstances in which the phenomena can be 
elicited reliably.
Bleuler
(1) coined the term loosening of associations to describe

Bleuler
the weakening of the connections between words and ideas thatbind thoughts into a coherent whole. While this term is a useful label for one of the major types of disorder of the form of speech and thought, it does not encompass the entire range of such disorders.In addition to disordered connections between words and ideas,there are oddities in the use of language. One of the most compre-hensive catalogues is the Thought, Language, and Communication Scale compiled by Andreasen.
(9) This scale includes several items that 
involve different aspects of the loosening of associations:
X Derailment—wandering off the point during the free ﬂ  ow of
conversation
X Tangentiality—answers to questions that are off the point
X Incoherence—a breakdown of the relationships between words 
within a sentence so that the sentence no longer makes sense
X Loss of goal—failure to reach a conclusion or achieve a point.

The Thought, Language, and Communication Scale also includes 
several items that refer to unusual use of language:
X Metonyms—unusual uses of words (e.g. hand-shoe instead of 
glove)
X Neologisms—new words invented by the patient.
The various aspects of loosening of associations and peculiarities 
of language use are commonly regarded as positive thoughtdis order. The Thought, Language, and Communication Scale also include negative thought disorders that entail impoverishmentof thinking:
X Poverty of speech—a disorder of the ﬂ  ow of speech in which the 
rate of speech production is reduced
X Poverty of content—the amount of information conveyed is rela-
tively little in proportion to the number of words uttered.
The Thought, Language, and Communication Scale has proved to

The Thought, Language, and Communication Scale has proved to 
be one of the most successful of recent attempts to deﬁ  ne and quan-
tify formal thought disorder, but it has several limitations. Most important of these is that the positive thought disorder items deﬁ  ned 
in the scale do not discriminate well between manic thought disor-der and ﬂ  orid schizophrenic thought disorder.
(10) Secondly, the scale 
is not sensitive to the subtle thought form disorders that occur in ﬁ rst-degree relatives of schizophrenic patients.These limitations are dealt with, at least partially, in the Thought 
Disorder Index devised by Holzman.
(11) This scale employs ratings 
based on thought and speech elicited by the Rorschach inkblot ﬁ gures and during an assessment of IQ. Two categories of disorder,

based on thought and speech elicited by the Rorschach inkblot ﬁ gures and during an assessment of IQ. Two categories of disorder, 
disorganization (comprising vagueness, confusion, and incoher-ence) and idiosyncratic verbalizations, appear to discriminate fairly well between schizophrenic and manic thought.
(11) Unfortunately, 
this scale is too cumbersome for routine clinical use.
Positive formal thought disorder is usually a transient feature of 
acute episodes of illness. Nonetheless, after resolution of the acute episode there is often a subtle residual thought disorder that is man-ifest as vague, wandering speech, or minor idiosyncrasies of word usage or ideas. Negative formal thought disorder has a greater ten-dency to be persistent. Chronic poverty of speech is associated with impairment in several domains of cognition
(12) including abstract

(12) including abstract 
reasoning. It leads to impaired social relationships,(13) although it is 
also inﬂ  uenced by the social milieu. Transient poverty of speech can 
occur during acute episodes of illness. At its most severe, the patient is mute.
Insight
Lack of insight is one of the deﬁ  ning characteristics of psychotic ill-
ness. Lack of insight entails a failure to accept that one is ill and to appreciate that symptoms are due to illness. In the International Pilot Study of Schizophrenia
(5) lack of insight occurred in approxi-

mately 90 per cent of cases. Insight is often partial. In particular, even in instances in which a patient acknowledges suffering from an illness, he or she might fail to accept that psychotic symptoms such as delusions or hallucinations are a manifestation of that illness. Lack of insight is one factor that contributes to unwillingness to accept treatment. However, the clinician should be aware that other factors, including lack of appropriate education about the ill-ness and justiﬁ  ed fear of side-effects of treatment, can also impede 
the development of a therapeutic collaboration between physician and patient.
Impaired cognition
In addition to delusions and disorders of thought form, a wide range of cognitive deﬁ  cits occur in schizophrenia. These are dis cussed in 
Chapter 4.3.3. This chapter focuses on the relationship between cog-nitive impairment and other features of the illness.

In the acute phase of the illness, attentional impairment is com-
mon and is often associated with psychomotor excitation and/or formal thought disorder. It might also reﬂ  ect preoccupation with 
delusions and hallucinations.
During the chronic phase of illness, many schizophrenic patients 
exhibit persistent cognitive impairments. Longitudinal studies of individuals who subsequently develop schizophrenia reveal thatthe deficits are discernible during childhood, suggesting thatthese deﬁ  cits are an aspect of the predisposition to schizophrenia. 
The major cognitive impairments are in the realm of executive 
function, working memory, and long-term memory. Executive

dysfunction includes impaired ability to initiate and select self-generated mental activity. Impaired ability to form and initiate plans is associated with chronic poverty of speech, blunted affect, and lack of spontaneous activity, while impaired ability to inhibit inappropriate responses is associated with chronic formal thought disorder.
(12)

529
Disorders of emotion
An extensive range of disorders of emotion occur in schizophrenia. 
Blunted affect and inappropriate affect are the most characteristic, and also tend to be the most persistent, but transient excitation, irritability, lability, and depression are also common.
Blunted affect
Blunting of affect is manifest as decreased responsivenessto emotional issues, loss of vocal inflection, and diminished facial expression. These objective signs of affective bluntingare sometimes accompanied by awareness of loss of emotional tone that, paradoxically, patients find to be distressing. More commonly, there is a lack of concern and even a lack ofawareness of the problem. Affective blunting is one of thehallmarks of chronic schizophrenia. Bleuler
(1) remarked that 
when the affects disappear, the illness becomes chronic. While blunted affect is usually chronic, it can also be a feature of acute episodes of the illness that resolves as the acute episode resolves.

Inappropriate affect
Inappropriate or incongruous affect is the expression of affect that is inappropriate in the circumstances. At its most severe it takes the form of hollow laughter that is unrelated to any apparent stimulus.
Excitation and depression
During acute exacerbations of schizophrenia, excitation, manifest as irritability, sleeplessness, agitation, and motor overactivity, is common. Depression is also common around the time of an acute episode of schizophrenia,
(14) and is often a feature of the prodro-
mal phase of the illness.
Depression also occurs during the chronic phase of the illness. 
The cross-sectional rate is approximately 10 per cent in the chronic phase,
(15) while in a longitudinal study, Johnson(16) found that
65 per cent of schizophrenic patients exhibited an episode of depression in a period of 36 months after a ﬂ  orid psychotic
episode.
Motor disorders and catatonia

episode.
Subtle disturbance of motor co-ordination is common. Home videos of children who subsequently develop schizophrenia dem-onstrate that even in infancy they are noticeably more clumsy than their siblings, suggesting that disturbed motor co-ordination is an aspect of the predisposition to schizophrenia.
(17)
Catatonia is a term embracing disorders of the initiation or 
organization of voluntary movement or posture. The most charac-teristic catatonic phenomena are:
XImmobility —absence of motor activity
XPosturing —adopting an unusual body posture
XWaxy ﬂ  exibility —allowing an examiner to adjust one’s posture, 
yielding like a warm candle
XNegativism —resisting manipulation by an examiner, with force 
proportional to that applied by the examiner

XStereotypy —aimless repetitive motor behaviourXMannerisms —apparently purposeful actions that appear odd 
because they are exaggerated in form or occur out of the usual context
XEcho phenomena —repetition of an examiners utterances or 
movements
XExcitement —excessive motor activity, usually accompanied by 
excessive mental activity.
These disorders can occur not only in schizophrenia, but also 
in other psychiatric or neurological disorder such as bipolar mood disorder or encephalitis, or alone as a primary disorder of motility.
Kahlbaum
(18) provided the classic description of catatonia. 
He emphasized not only the typical phenomena but also a charac-teristic time course, in which a prodromal phase dominatedby melancholic symptoms evolved into a ﬂ  uctuating disorder

in which episodes of diminished motility typically lasting forseveral weeks or months, were interspersed in periods of nearnormal function, but with a tendency towards eventual dementia in many cases. Episodes were often accompanied by confusion and in some instances, a state of stupor. In some cases, episodes ofexcitation occurred as well. While Kahlbaum’s emphasis on both characteristic phenomena and time course laid a foundation for the subsequent delineation of major mental illnesses at the end of the nineteenth century and in particular, for Kraepelin’s delinea-tion of schizophrenia,
(7) it is probably best to regard catatonia as a 
cluster of clinical features that can occur within various different illnesses.
Two major forms are retarded catatonia, characterized by slowed

Two major forms are retarded catatonia, characterized by slowed 
or diminished activity; and excited catatonia in which the domi-nant feature is excessive motor activity. Many variants of catatonia differing in the relative prominence of the characteristic features; or in the associated features such as autonomic instability; or in time course, have been reported in the past 150 years. Fink and Taylor
(19) argue on the grounds similarity of clinical features and

(19) argue on the grounds similarity of clinical features and 
response to treatment (with benzodiazepines and/or ECT) that the variants of catatonia share a common brain pathophysiology, though different predisposing or precipitating factors might lead to variation in clinical features and time course. The variants include malignant catatonia, in which there is a sudden onset of excitation, associated with fever and autonomic instability, leading to fatal outcome in a substantial proportion of cases. The relationship between malignant catatonia and neuroleptic malignant syndrome (NMS), which is characterized by features very similar to malig-nant catatonia, but is triggered by antipsychotic medication, is an issue of practical clinical importance. A careful review nine cases of NMS and 17 cases of malignant catatonia by Carroll and Taylor
(20)
failed to ﬁ  nd differences in clinical features, supporting the conclu-
sion that NMS is a form of catatonia.
Disorders of volition

(20)
Among the most disabling of the clinical phenomena of schizo-phrenia are disruptions of motivation and will. Voluntary activity can be disjointed or weakened. Disjointed volition is manifest in poorly organized ill-judged activities which appear to be prompted by impulse. For example, an artistic, intelligent young woman felt cold so she lit a ﬁ  re on the carpet in her bedroom, even though she 
was able to appreciate that this was a dangerous thing to do. 4.3.2. descriptive clinical features of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 530
Weakened volition results in prolonged periods of underactivity. 
The patient might lie in bed or sit in an armchair for hours.
Anxiety and somatoform disorders
Various forms of anxiety and somatic symptoms are common in schizophrenia. Huber
(21) described a non-characteristic defect state 
which is dominated by anxiety and asthenia. Coenesthesia, in which the patient suffers unusual or debilitating bodily experiences that do not have an apparent somatic cause, occurs frequently.
Dimensions of psychopathology in 
Schizophrenia is heterogeneous in its clinical presentation, suggest-
ing that several different pathophysiological processes might contribute to the illness.
Positive and negative symptom dimensions
Positive symptoms are those that reﬂ  ect the presence of an abnor-
mal mental process, and include delusions, hallucinations, and formal thought disorder. Negative symptoms reﬂ  ect the diminu-

tion or absence of a normal mental function. They include poverty of speech and blunted affect. In schizophrenia, positive symptoms tend to be transient, while negative symptoms tend to be chronic. In an influential hypothesis, Crow
(22) proposed that positive 
symptoms arise from dopaminergic overactivity, while negative symptoms reﬂ  ect structural brain abnormality. While this hypoth-
esis is consistent with a substantial body of evidence, it does not account adequately for the complexity of the heterogeneity of the clinical features in schizophrenia.
Three dimensions of characteristic symptoms
The preponderance of evidence(12, 13, 23) from factor analysis of

The preponderance of evidence(12, 13, 23) from factor analysis of 
schizophrenic symptoms indicates that the characteristic symp-toms of schizophrenia segregate into three syndromes, as shown in Table 4.3.2.2. These syndromes do not reﬂ  ect separate illnesses, but 
different dimensions of illness, in the sense that a patient might exhibit more than one of the syndromes.
The three syndromes embrace only the characteristic symptoms 
that are given weight in making a diagnosis of schizophrenia. In addition, there are two affective syndromes, depression and psychomotor excitation, which are prevalent in schizophrenia,
(12)despite being more characteristic of mood disorders. These affec-tive syndromes are usually transient.
An accumulating body of evidence
(12) from brain imaging 
studies indicates that the three characteristic syndromes are associ-

ated with three distinguishable patterns of cerebral malfunction involving the areas of association cortex and related subcortical nuclei, which serve higher mental functions. In an individual case, several of these neural systems might be involved.
Although many details of the relationships between the diverse 
clinical features of schizophrenia remain uncertain, a growing understanding of the neural pathways involved is beginning to provide the foundation for understanding the protean manifesta-tions of this disorder.
Cutting, J. (2003). Descriptive psychopathology. In Schizophrenia , Chap. 2 
(2nd edn) (eds. S.R. Hirsch and D. Weinberger), pp. 15–24. Blackwell, Oxford.
Fuller, R.L.M., Schultz, S.K., and Andreasen, N.C. (2003). The symptoms of 
schizophrenia. In Schizophrenia , Chap. 3 (2nd edn) (eds. S.R. Hirsch

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12. Liddle, P .F. (1999). The multi-dimensional phenotype of schizophrenia. 
In Schizophrenia in a molecular age  (ed. C.A. Taminga), pp. 1–28. 
American Psychiatric Press, Washington, DC.
13. Liddle, P .F. (1987). The symptoms of chronic schizophrenia: a 
re-examination of the positive-negative dichotomy. The British Journal 
of Psychiatry ,151, 145–51.
14. Siris, S.G. (1991). Diagnosis of secondary depression in schizophrenia: 
implications for DSMIV . Schizophrenia Bulletin ,17, 75–98.
15. Barnes, T.R.E., Curson, D.A., Liddle, P .F., et al. (1989). The nature 
and prevalence of depression in chronic schizophrenic inpatients. The British Journal of Psychiatry ,154, 486–91.Table 4.3.2.2  Three syndromes of symptoms characteristic of 
Reality distortion
 Delusions Hallucinations
Disorganization

 Thought form disorder
 Inappropriate affect
 Bizarre behaviour
Psychomotor poverty (core negative symptoms)
 Poverty of speech Blunted affect Decreased spontaneous movement

531
16. Johnson, D.A.W. (1988). The signiﬁ  cance of depression in the 
prediction of relapse in chronic schizophrenia. The British Journal of 
Psychiatry ,152, 320–3.
17. Walker, E. and Lewine, R.J. (1990). Prediction of adult-onset 
schizophrenia from childhood home videos of the patients. The American Journal of Psychiatry ,89, 704–16.
18. Kahlbaum, K.L. (1874; translated 1973). Die Katatonie oder das 
Spannungsirresein . Verlag August Hirschwald, Berlin, 1874. Translated: 
Kahlbaum, K. Catatonia. Translated by Y. Levis and T. Pridon. Johns Hopkins University Press, Baltimore, 1973.
19. Fink, M. and Taylor, M.A. (2003). Catatonia. A clinicians guide to 
diagnosis and treatment . Cambridge University Press, Cambridge.
20. Carroll, B.T. and Taylor, B.E. (1997) The nondichotomy between lethal 
catatonia and neuroleptic malignant syndrome. Journal of Clinical 
Psychopharmacology ,17, 235–36.
21. Huber, G., Gross, G., and Schuttler, E. (1975). A long term follow-up

21. Huber, G., Gross, G., and Schuttler, E. (1975). A long term follow-up 
study of schizophrenia: psychiatric course of illness and prognosis. Acta Psychiatrica Scandinavica ,52, 49–57.
22. Crow, T.J. (1980). The molecular pathology of schizophrenia: more 
than one disease process. British Medical Journal ,280, 66–8.
23. Arndt, S., Andreasen, N.C., Flaum, M., et al. (1995). A longitudinal 
study of symptom dimensions in schizophrenia. Archives of General 
Psychiatry ,52, 352–60.
4.3.3 The clinical neuropsychology 
of schizophrenia
Impairments in a variety of cognitive functions are found in

Impairments in a variety of cognitive functions are found in 
patients with schizophrenia. These impairments affect a widearray of different cognitive abilities and are often quite severe,when compared to standards based on healthy individuals ofthe same age, education levels, and gender. Cognitive impairments appear to be present across the lifespan, detectable at the timeof the ﬁ  rst treatment episode, if not before, and to manifest a
generally stable course over time. Although the current knowl-edge base regarding cognition in schizophrenia is quite broad, additional research information is constantly accruing. The main purpose of this chapter is to provide a broad overview of the domains, severity, and course of cognitive impairments inschizophrenia, with a focus on functional relevance and treat-ment possibilities.
History

History
Cognitive impairments were reported by both Emil Kraepelin and 
Eugen Bleuer, both of whom noted that they believed thatcognitive impairments were amongst the core features of the
illness. The conception of dementia praecox introduced by Kraepelin focused on the cognitive and functional deﬁ  cits in the 
illness and likened the condition to a condition such as Alzheimer’s disease with an earlier onset age. Over the ﬁ  rst half of the twenti-
eth century research on cognition in schizophrenia focused on a variety of different topics, including memory, attention, andlanguage skills.
(1)Clinical neuropsychology and schizophrenia

The development of clinical neuropsychology and formalized neuropsychological (NP) tests led to a substantial increase in inter-est in cognition in schizophrenia. Classical NP ability domains, as well as the types of tests typically used to assess them are presented in Table 4.3.3.1. Clinical NP assessments develop an understanding of areas of relative strength and weakness, comparing current func-tioning following illness or injury to evidence or estimates regarding 
prior functioning.
(2) Then a proﬁ  le can be developed, contrasting 
better or more poorly performed ability areas. Performance across these ability areas can be converted to standard scores, considering demographic factors that influence performance such as age,education level, and sex.
(3) Thus, the results of a clinical NP assess-

ment provide a summary of relative strengths and weaknesses. Clinical NP assessment has moved away from earlier effortsto anatomically localize deficits through test performance or to distinguish ‘functional’ versus ‘organic’ impairments. The current conception of neuropsychological performance is largely based on the concept of functional neural networks, which link cortical and subcortical regions through patterns of linked activa-tion during task performance.
(4)
Table 4.3.3.1  Important cognitive ability domains and tests
Ability areas Tests
Perceptual skills Pattern recognition

(4)
Motor skills Manual dexterityAttention Sustained attention Continuous performance tests Selective attention Resistance to distractionWorking memory Spatial working memory Spatial delayed response tests Verbal working memory Measures of verbal memory spanEpisodic memory Verbal memory List learning; paragraph recall Non-verbal memory (spatial memory) Object learning tests Procedural memory Pursuit rotor; mirror writing Long-term semantic memory Word recognition readingExecutive functions Concept formation Comprehension tests Reasoning Proverb interpretation Problem-solving Wisconsin card sort; Tower of 
London
 Inhibition Stroop test Processing speed Trail-making ; digit symbolVerbal skills Naming Object naming test Verbal ﬂ  uency Animal naming4.3.3 the clinical neuropsychology of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 532
Cognitive impairment in schizophrenia
Severity
Patients with schizophrenia demonstrate impaired performance 
on NP tests measuring a variety of ability areas. As shown in Table 4.3.3.2, impairments across abilities range from mild to severe.
(5) Further, aspects of spared functioning are quite rare, with 
patients performing at levels worse than population means on nearly all domains other than reading skills, object naming, and recognition memory. These impairments are not due to poor motivation or the presence of psychosis
(6); it is well understood 
that patients demonstrate persistent NP impairments following recovery from acute psychotic episodes and that cognitive impair-ments are quite stable over time.
Proﬁ  le
It is important to consider that patients with schizophrenia show 
considerably smaller overall decline in intelligence than in some speciﬁ  c ability areas.
(7) The majority of these impaired domains

(7) The majority of these impaired domains 
are often seen to be those that are associated with the functions of the frontal lobe. However, the notion that the whole array of cognitive impairments seen in schizophrenia could originate from a single localized lesion is implausible, as impairments in cognitive functions that are impaired individuals with medial temporal-hippocampal lesions are also quite profound in patients with schizophrenia.
(8)There has been considerable debate about the structure of cog-
nitive deﬁ  cits in schizophrenia. This debate has focused on whether 
the proﬁ  le of relative deﬁ  cits is generalized, with similar severity 
across all components, or speciﬁ  c.(9) Proponents of the speciﬁ  c 
proﬁ le argument often site evidence of regional brain dysfunction 
detected with neuroimaging procedures(10) or more extreme deﬁ  -

cits on certain NP tests such as episodic memory.(8) There have 
been recent factor analytic studies that found complex solution with up to six factors
(11) and other studies that found a single 
factor characterized all of the cognitive data in large samples.(12)
It does seem that tests requiring cognitive capacity and processing speed are amongst the most poorly performed and that tests examining the ability to use information acquired prior to the onset of schizophrenia are performed best.
Onset
At the time of the ﬁ  rst treatment for schizophrenia, either inpatient 
or outpatient, people who receive the diagnosis perform in a manner that is nearly as impaired as more chronic patients, with a similar proﬁ  le of impairment.
(13) These data support the idea that 
cognitive impairment is not continuously progressive over the entire course of illness.

(14) It is clear, however, that cognitive impair-
ments may also be detectable in at least some people who are destined to develop schizophrenia. In population-based studies of apparently healthy individuals being screened for induction into compulsory military service, there are clear group differences in performance between individuals who eventually develop schizo-phrenia and those who do not.
(15) These impairments have some 
level of sensitivity and speciﬁ  city, but are clearly not diagnostic 
indicators at that stage. Findings of impairments in cognition prior to the patient’s meeting formal diagnostic criteria for the illness do provide additional suggestions that cognitive deﬁ  cits are central 
features of the illness.
Cognitive decline in schizophrenia?

While the course of cognitive impairments in schizophrenia appears generally stable over the lifespan, there is a substantial minority of patients with schizophrenia who manifest considerable cognitive impairments that worsen over time. The patients who show these changes tend to be older and with a chronic course of treatment-refractory positive symptoms, often accompanied by a lifetime of institutional care.
(16) Longitudinal studies have suggested 
that younger institutionalized patients with similarly severe positive do not show declines during similar follow-up periods,
(17)
suggesting that there may be age-associated vulnerability to decline. Studies from multiple research sites have found a low prevalence of neurodegenerative changes at post-mortem in older schizophrenia patients,
(18) suggesting that these abnormalities cannot be fully

(18) suggesting that these abnormalities cannot be fully 
explained by degenerative conditions. At present, there is no infor-mation on whether these changes could be due to the experience of institutionalization alone, but studies of patients who were released from chronic psychiatric care have not shown evidence of reversal of these cognitive impairments. As patients with schizo-phrenia have evidence of considerable reduction in their ‘cognitive reserve’ , based on the lower levels of premorbid functioning, it would expected that a variety of risk factors could lead to cognitive changes, including subclinical neurodegenerative pathology, vascu lar 
abnormalities, or other factors which can influence cognitive impairments in older individuals.Table 4.3.3.2  Level of impairment in cognitive abilities in 
Mild Moderate Severe
Perceptual skills X
Motor skills XAttention
 Sustained attention X
 Selective attention X
 Spatial working memory X

 Verbal working memory X
Episodic memory
 Verbal learning X Non-verbal memory (spatial memory) X Delayed recall X Delayed recognition X
Procedural memory XLong-term factual memory XExecutive functions XProcessing speed XVerbal skills
 Naming X
 Verbal ﬂ  uency X
See Heinrichs and Zakzanis(5) for a description of the methods used to evaluate these levels 
of impairment.

533
Presence in relatives and individuals with ‘spectrum’ 
conditions
Cognitive impairments are present in the relatives of people with 
schizophrenia and these impairments have evidence of heritability. Longitudinal studies have suggested that some aspects of cognitive impairment, such as attentional deﬁ  cits, predict the development 
of psychotic symptoms in high risk children with at least one schizophrenic parent.
(19) Further, individuals with schizophrenia 
spectrum conditions such as schizotypal personality disorder (SPD) show evidence of cognitive deﬁ  cits similar in proﬁ  le, yet 
reduced in severity compared to people with schizophrenia.
(20)

(20)
As patients with SPD do not have a markedly increased risk for schizophrenia, some aspects of cognitive functioning may repre-sent a stable correlate of some aspects of the predisposition to schizophrenia. While studies have been in process to identify candidate cognitive processes as potential genetically mediated intermediate phenotypes,
(21) speciﬁ  c gene-performance correla-
tions are not large enough in magnitude yet to demonstrate that any cognitive impairment is clearly related to speciﬁ  c susceptibility 
genes for schizophrenia.
Functional relevance
One of the reasons for the increased interest in NP impairment in schizophrenia over the past decade is the developing understand-ing of the functional relevance of NP impairment. In speciﬁ  c, NP

One of the reasons for the increased interest in NP impairment in schizophrenia over the past decade is the developing understand-ing of the functional relevance of NP impairment. In speciﬁ  c, NP 
impairment in schizophrenia is the single strongest correlate of impairments in everyday living skills, in social outcomes, and in seeking and maintaining employment or other productive activi-ties. This realization was spurred by several high-proﬁ  le reviews 
of the literature
(22) and a developing interest in both disability 
reduction and the direct measurement of disability. While the correlations between impairments in individual NP ability areas and speciﬁ  c aspects of everyday disability are only moderate in size, 
correlations between composite measures of multiple NP domains and global measures of outcome are often fairly substantial, in the range of Pearson correlations of r = 0.7 (reﬂ  ecting 50 per cent

correlations between composite measures of multiple NP domains and global measures of outcome are often fairly substantial, in the range of Pearson correlations of r = 0.7 (reﬂ  ecting 50 per cent 
shared variance). In contrast, in similar studies, the cross-sectional correlation between the severity of psychotic (i.e. positive) symp-toms is often closer to r = 0.1, reﬂ  ecting about 1 per cent shared 
variance.
(12) This difference in correlations is likely accentuated by 
the unstable and episodic nature of positive symptoms, in contrast to both functional disability and NP performance, which are both known to be quite stable over time.
Studies of the ability to perform skilled acts (i.e. independent 
living and social skills) in analogue situations have found that the correlation between impairment on NP tests and deﬁ  cits in 
‘functional capacity’ is greater than the correlation between NP performance and real world functional performance.
(23) This

(23) This 
difference in correlations is probably due to the fact that there are multiple factors other than ability that determine everyday outcomes. Opportunities, disability compensation, environmental support, and familial resources are all factors that could lead to discrepancies between what a person can do (i.e. their competence) and what they actually do (i.e. their everyday performance). The fact that disability, in terms of reduced competence, can be meas-ured directly with performance-based tests is quite important, as some of these measures could actually be used in everyday clinical practice or as outcomes in treatment studies.Treatment of cognitive impairment 
in schizophrenia
Although antipsychotic medications have been shown for years to

Although antipsychotic medications have been shown for years to 
be effective in reducing psychotic symptoms in about 70 per cent of patients with schizophrenia, effects on cognitive impairments are much smaller. Although cognitive impairments are apparently not worsened by conventional antipsychotic treatments, their beneﬁ  cial effects are small and limited to a subset of cognitive 
domains. Atypical antipsychotic treatment appears to have a some-what greater effect, suggested by meta-analyses and large-scale studies to be about 0.25 standard deviations.
(24) Given the substantial
magnitude of impairments in the illness, this level of improvement does not come close to normalization for most patients.
Targeted treatments aimed at cognitive functioning have come

Targeted treatments aimed at cognitive functioning have come 
from both pharmacological and cognitive remediation domains. Most pharmacological interventions have had quite modest effects, while the results of recent cognitive remediation interventionshave been more promising. At least three different interventions, using computerized interventions in randomized trials haveshown both cognitive improvements and generalization of impro-vement to functionally relevant aspects of everyday outcome.
(25)
Concurrent antipsychotic treatments may be responsible for the poor outcomes of pharmacological interventions, as some ofthese treatments that have shown minimal beneﬁ  ts in patients
with schizophrenia receiving antipsychotic treatments haveshown beneﬁ  cial effects in healthy individuals and in persons with

with schizophrenia receiving antipsychotic treatments haveshown beneﬁ  cial effects in healthy individuals and in persons with 
schizotypal personality disorder. This is an issue that will require further study.
Cognitive impairments in schizophrenia are related to the functional disability in the illness and may produce much of the morbidity associated with the condition. These impairments are wide ranging and are found in multiple important domains, with onset at the time of, or in many cases, prior to the ﬁ  rst episode 
of illness. No single focal lesion appears responsible for the array of deﬁ  cits seen. Relatives of people with schizophrenia and indi-
viduals with non-psychotic schizophrenia-spectrum conditions are also affected by these cognitive deﬁ  cits. Cognitive impairments 
have proven difﬁ  cult to treat, but multiple initiatives are under-

way to improve treatment success. Both pharmacological and cognitive remediation interventions are being studied in detail at this time.
Resources: National Association for Research in Schizophrenia and Affective 
Disorders (NARSAD). Promotes research on these topics for junior to distinguished investigators.
Websites: Schizophrenia Research Forum. The ultimate resource for new 
developments in schizophrenia. http://www.schizophreniaforum.org/
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schizophrenia . Appleton, Century, Crofts, New Y ork.
 2. Lezak, M.D., Howieson, D.B., and Loring, D.W. (2004). 
Neuropsychological assessment  (4th edn). Oxford, New Y ork.4.3.3 the clinical neuropsychology of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 534
 3. Heaton, R.K., Miller, S.W., Taylor, M.J., et al. (2005). Revised 
comprehensive norms for an expanded Halstead-Reitan Battery
(HRB): demographically adjusted neuropsychological norms for African American and Caucasian adults . Psychological Assessment Resources, 
Lutz, FL.
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aging cognition, and neuromodulation. Neuroscience and Biobehavioral 
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schizophrenia: a quantitative review of the evidence. Neuropsychology ,
12, 426–45.
 6. Elevevag, A. and Goldberg, T.E. (2000). Cognitive impairment 
in schizophrenia is the core of the disorder. Critical Reviews in 
Neurobiology ,14, 1–21.
 7. Weickert, T.W., Goldberg, T.E., Gold, J.M., et al. (2000). Cognitive

 7. Weickert, T.W., Goldberg, T.E., Gold, J.M., et al. (2000). Cognitive 
impairments in patients with schizophrenia displaying preservedand compromised intellect. Archives of General Psychiatry ,
57, 907–13.
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function in schizophrenia. Selective impairment in memory and learning. Archives of General Psychiatry ,48, 618–24.
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and speciﬁ  c cognitive deﬁ  cits in schizophrenia. Biological Psychiatry ,
55, 826–33.
10. Hazlett, E.A., Buchsbaum, M.S., Jeu, L.A., et al. (2000). Hypofrontality 
in unmedicated schizophrenia patients studied with PET during performance of a serial verbal learning task. Schizophrenia Research ,
43, 33–46.
11. Gladsjo, J.A., McAdams, L.A., Palmer, B.W., et al. (2004). A six-factor

43, 33–46.
11. Gladsjo, J.A., McAdams, L.A., Palmer, B.W., et al. (2004). A six-factor 
model of cognition in schizophrenia and related psychotic disorders: relationships with clinical symptoms and functional capacity. Schizophrenia Bulletin ,30, 739–54.
12. Keefe, R.S., Bilder, R.M., Harvey, P .D., et al. (2006). Baseline 
neurocognitive deﬁ  cits in the CATIE schizophrenia trial. 
Neuropsychopharmacology ,31, 2033–46.
13. Saykin, A.J., Shtasel, D.L., Gur, R.E., et al. (1994). Neuropsychological 
deﬁ cits in neuroleptic naive patients with ﬁ  rst-episode schizophrenia. 
Archives of General Psychiatry ,51, 124–31.
14. Heaton, R.K., Gladsjo, J.A., Palmer, B.W., et al. (2001). Stability and 
course of neuropsychological deﬁ  cits in schizophrenia. Archives of 
General Psychiatry ,58, 24–32.
15. Davidson, M., Reichenberg, A., Rabinowitz, J., et al
. (1999). Behavioral 
and intellectual markers for schizophrenia in apparently healthy male

and intellectual markers for schizophrenia in apparently healthy male 
adolescents. The American Journal of Psychiatry ,156, 1328–35.
16. Harvey, P .D., Silverman, J.M., Mohs, R.C., et al. (1999). Cognitive 
decline in late-life schizophrenia: a longitudinal study of geriatric chronically hospitalized patients. Biological Psychiatry ,45, 32–40.
17. Friedman, J.I., Harvey, P .D., Coleman, T., et al. (2001). Six-year 
follow-up study of cognitive and functional status across the lifespan in schizophrenia: a comparison with Alzheimer’s disease and normal aging. The American Journal of Psychiatry ,158, 1441–8.
18. Arnold, S.E., Gur, R.E., Shapiro, R.M., et al. (1995). Prospective 
clinicopathological studies of schizophrenia: accrual and assessment of patients. The American Journal of Psychiatry ,152, 731–7.

19. Cornblatt, B.A. and Erlenmeyer-Kimling, L. (1985). Global attentional 
deviance as a marker of risk for schizophrenia: speciﬁ  city and 
predictive validity. Journal of Abnormal Psychology ,94, 470–86.
20. Mitropoulou, V ., Harvey, P .D., Zegarelli, G., et al. (2005). 
Neuropsychological performance in schizotypal personality disorder: importance of working memory. The American Journal of Psychiatry ,
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21. Goldberg, T.E., Egan, M.F., Gscheidle, T., et al. (2003). Executive 
subprocesses in working memory: relationship to catechol-O-
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Determinants of real-world functional performance in schizophrenia subjects: correlations with cognition, functional capacity, and symptoms. The American Journal of Psychiatry ,163, 418–25.
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and supported employment for persons with severe mental illness: 
one-year results from a randomized controlled trial. Schizophrenia 
Bulletin ,31, 898–909.
4.3.4 Diagnosis, classiﬁ  cation, 
and differential diagnosis of schizophrenia
The diagnosis of schizophrenia

Until the early 1970s, the diagnosis of schizophrenia was one of the 
most contentious and fraught issues in the whole of psychiatry. Since then a massive international effort has been put in motion out of which explicit diagnostic criteria emerged. Some achieved widespread and even multinational agreement, allowing the pains-taking process of calculating diagnostic speciﬁ  city, sensitivity, 
reliability, and (perhaps) validity to begin. Although criticism of the diagnosis of schizophrenia continues, mostly from outside psychiatrists, the vast majority of psychiatrists look upon the major sets of diagnostic criteria with weary acceptance, seeing them as ﬂ awed but useful and possibly ‘as good as it gets’ given our current 
state of knowledge/ignorance.
Throughout the 1970s and early 1980s there was an overabun-

dance of criteria including the St. Louis criteria
(1) and the Research 
Diagnostic Criteria,(2) followed by the Present State Examination 
(PSE-CATEGO), the ICD-9, and the DSM-III. Perhaps because of the ‘cookbook’ explicitness of the DSM-III or the pervasive inﬂ uence of American psychiatric practice, dubbed by some ‘neo-
colonial’ , the DSM, in its fourth revision with a ﬁ  fth due in 2010, 
is the mostly widely used. The ICD-10 is also used throughout the world, but seldom in North America.
The signs and symptoms of schizophrenia and related disorders are discussed in detail in Chapter 4.3.2. Also, the diagnostic process is described in general in Chapter 1.8.1. As noted, the signs and symptoms, weighted in terms of their typicality or speciﬁ  city, com-

bined with additional clinical factors such as onset, duration, social consequences, etc., are used to make a diagnosis of schizophrenia and subsequently to classify the disorder into subtypes. The DSM and ICD criteria are described below (Tables 4.3.4.1–4.3.4.3).

535
Another group of psychotic disorders which may be distin-
guished on the basis of formal phenomenological properties are the delusional disorders
(3, 4) formally known as paranoia (see 
Chapter 4.4).
Basis of classiﬁ  cation
Atheoretical: Schneider’s ﬁ  rst-rank symptoms
These are still important for the diagnosis of schizophrenia using 
the ICD-10 frame of reference. They are too rare to achieve high levels of sensitivity and their specificity has been challenged. Nevertheless, ﬁ  rst-rank symptoms perform creditably on these 
parameters when compared to negative symptoms.
(5,6) On the other hand, the lack of aetiological and prognostic signiﬁ  cance of 
ﬁ rst-rank symptoms has undermined the prominence claimed for 
them.(7,8) The negative(9) or so-called deﬁ  cit syndrome(10) relates

them.(7,8) The negative(9) or so-called deﬁ  cit syndrome(10) relates 
more consistently to outcome/prognosis and shows more stability over time. The constituent symptoms such as social withdrawal, apathy, lack of initiative, and self-care, have rather poor diagnostic speciﬁ  city in isolation and must be distinguished from depression 
and parkinsonism, chronic drug dependence, and organic brain damage.
Theoretical
Attempts at a theoretical classiﬁ  cation have been made. The ﬁ  rst in 
the modern era was Crow’s Type I and Type II distinction,(11)Table  4.3.4.1  Major diagnostic criteria for schizophrenia
DSM-IV ICD-10
Characteristic symptoms
 One or more for 1 month 1. Bizarre delusions 1. Thought echo/insertion/ withdrawal/broadcasting
2. Commenting voice or voices conversing 2. Delusions of control
3. Hallucinatory voices
4. Persistent delusions
 Or two or more 1. Delusions 1. Persistent hallucinations

2. Hallucinations 2. Thought block/disorder3. Disorganized speech 3. Catatonia4. Grossly disorganized or catatonic behaviour 4. Negative symptoms5. Negative symptoms 5. Signiﬁ  cant personality change
Time course 1 month (‘signiﬁ  cant proportion’) for symptoms listed 
plus 6 months social/occupational disturbance1 month (most of the time)
Exclusions Schizoaffective disorder or brief mood disturbance
Direct effect of drugs of abuse/ medication or general 
medical conditionExtensive depressive/manic symptoms or diagnosis of schizoaffective disorder
Overt brain disease; drug intoxication/withdrawal
Table 4.3.4.2  Criteria for the diagnosis of schizophrenia subtypes
Schizophrenia subtypes DSM-IV ICD-10
Paranoid One or more delusions plus frequent auditory hallucinations; no

Paranoid One or more delusions plus frequent auditory hallucinations; no 
prominent thought disorder, catatonia, or negative symptomsDelusions, hallucinatory voices, hallucinations in other modalities; 
disturbances of affect, volition, and speech ‘inconspicuous’
Disorganized DSM
Hebephrenic ICDProminent disorganized speech behaviour and ﬂ  at/inappropriate 
affect; no catatoniaProminent disturbances of affect, volition, and thought; 2–3 
months duration; adolescents/young adults only
Catatonic Two of motoric immobility, excessive activity, negativism, peculiar 
voluntary movements, echolalia/ praxiaOne or more of stupor, excitement. posturing, negativism, rigidity, 
waxy ﬂ  exibility, automatic compliance and perserveration
Undifferentiated Meets criteria for schizophrenia but none of the above subtypes Meets criteria for schizophrenia but none of the  above subtypes

Undifferentiated Meets criteria for schizophrenia but none of the above subtypes Meets criteria for schizophrenia but none of the  above subtypes 
plus residual
Residual Absence of prominent characteristic symptoms (but two or more 
must be present in attenuated form); continuing evidence of 
disturbance including negative symptomsProminent negative symptoms; clear-cut episode(s) in past; at least 
1 year history; no dementia or depression etc.
Simple Slowly progressive negative symptoms without other psychotic 
symptoms(See schizoid personality disorder)4.3.4 diagnosis, classification, and differential diagnosis of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 536
although it echoes older notions of ‘process’-chronic and deterio-
rating versus ‘reactive’ (relapsing and remitting) typologies. The innovation was to link the distinction with proposed differences in dopamine receptor hyperactivity (Type I), associated with positive symptoms and good response to dopamine antagonist drugs, and on the other hand, to neurological damage (Type II) as evidenced by ventricular enlargement on Computerized T omography (CT) 
brain scans, associated with chronicity, poor premorbid function-ing, and poor response to treatment.
Building on this was the ‘aetiological classiﬁ  cation’ proposed by 
Murray et al .
(12) which contrasted cases with a presumed genetic

(12) which contrasted cases with a presumed genetic 
aetiology and those who had other putative risk factors such as early brain damage (see Chapter 4.3.6.1). Although these attempts have served as useful stimuli for research, they have not been found to aid clinical decision-making and in fact now appear to support a blurring of diagnostic boundaries rather than a sharpening or sub-division.
(13) In fact the search for ‘biological markers’ often called 
‘endophenotypes’ , which might validate diagnostic distinctions continues. Take for example, the presence of ventricular enlarge-ment or cortical thinning, ﬁ  rst detected using CT and now magnetic 
resonance imaging ( MRI ). Meta-analyses have conﬁ  rmed that 
indices of ‘cerebral atrophy’ are strongly associated with schizo-phrenia but the effect sizes are small.
(14) Medial temporal lobe

(14) Medial temporal lobe 
structures are the region of most grey matter volume loss. However, there is substantial overlap between normal controls and schizo-phrenia cases and MRI cannot be considered a useful diagnostic test. A host of genetic markers have been identiﬁ  ed in the last 
5 years, each of small effect and some showing overlap between the 
major schizophrenic and affective syndromes.
(15)
Positive family history remains an important ﬁ  nding in the 
psychiatric history of an individual patient. Although none of the diagnostic criteria permits the inﬂ  uence of family history, in clini-
cal settings, ‘odd’ or withdrawn behaviour takes on a very different 
meaning if seen in the ﬁ  rst-degree relative of someone with a ﬁ  rm 
schizophrenia diagnosis.
Early diagnosis?

The premorbid personality in schizophrenia is typically described as emotionally and socially detached. Such people have few friends, 
are often cold and aloof, and engage in solitary occupations. Their behaviour may be eccentric and they are indifferent to praise or criticism. Recent studies, including United Kingdom national cohort studies
(16) and a Swedish conscript cohort study(17) indicate 
that children who later develop schizophrenia are more likely to have lower IQs and educational achievements than other children. They are also more likely to have interpersonal and behavioural difﬁ culties. Parents recognize ‘preschizophrenic’ children as being

different from their other siblings. However, such characteristics are very common in the general population so have virtually no positive predictive value.
Early diagnosis is only successful when based on psychotic symp-
toms. Here the diagnosis of schizophreniform psychosis (DSM-IV) and the acute schizophrenia-like psychotic disorder of the ICD-10 are relevant. The former must last for more than 1 but less than 6 months (otherwise the diagnosis is brief reactive psychosis). Hence the disorder is substantial by any common-sense deﬁ  nition, 
and unsurprisingly many cases (70 per cent) go on to develop full-blown schizophrenia, affective disorder, or schizoaffective disorder.
(18) The temporal stability of the diagnosis is poor, with 
around 30 per cent recovering over follow-up periods averaging 16 months in one study.
New services have built up around ever earlier diagnosis with

New services have built up around ever earlier diagnosis with 
the explicit aim of secondary or even primary prevention. Criteria have been developed for the diagnosis of high-, ultra-high, or so-called ‘at-risk’ mental states based on transient psychotic experi-ences—even briefer than schizophreniform or more persistent disturbances in the sense of self (‘basic symptoms’) which fall short of true psychosis.
(19,20) One impetus to this being the discovery 
that most patients when ﬁ  rst ill endure a long duration—months 
or years—of untreated psychosis (DUP).
Other psychiatric disorders
(a) Other psychoses
It could be argued that distinguishing schizophrenia from schizoaf-fective disorder, schizophreniform disorder, delusional disorder, etc. is an academic exercise. Despite passing enthusiasms, treatment in psychiatry is largely symptom or syndrome based.
(21) Thus

(21) Thus 
manic symptoms respond to antimanic agents including lithium, psychotic symptoms respond to ‘neuroleptics’ or ﬁ  rst and now 
second-generation antipsychotic drugs (SGA), and depressive symptoms respond to antidepressants. Other ‘mood-stabilizing’ agents are also of value especially when combined with antipsy-chotics. Several SGAs are licensed for bipolar affective disorder and schizoaffective disorder although it is not clear whether they have distinct advantages over older drugs in this regard. Clozapine remains the only antipsychotic medication which is proven to be effective in at least some patients who are otherwise treatment resistant. However, it is possible that with increasing clinical expe-rience and research more speciﬁ  c indications for newer agents will 
emerge. This will depend on the preservation of skills in history 
taking and the mental state examination, and a careful attitude

taking and the mental state examination, and a careful attitude 
towards making a diagnosis rather than use of sloppy catch-all labels such as ‘serious mental illness’ favoured by healthcare planners.
The prognostic signiﬁ  cance of a diagnosis of schizophrenia 
(versus schizoaffective and affective disorders) has been discussed in Chapters 4.3.7 and 4.3.9. Although predicting outcome in indi-vidual patients is notoriously difﬁ  cult because of the inﬂ  uence Table 4.3.4.3  Terminology used to describe the course of 
schizophrenia in the DSM-IV and ICD-10 classiﬁ  cations
Continuous Continuous
Episodic with residual symptoms Episodic with stable deﬁ  citEpisodic with no interepisode symptoms Episodic remittent
Single episode in partial remission Incomplete remission
Single episode in full remission Complete remissionOther Other 
Episodic with progressive deﬁ  cit

aCourse speciﬁ  ers in both DSM-IV and ICD-10 require 1 year of observation.

537
of idiosyncratic factors such as services, relationships within the 
family, compliance, intelligence, personality, demographics, etc., the more a disorder approaches ‘typical’ schizophrenia, the poorer the prognosis tends to be.
That said, schizoaffective disorder is the closest disorder, 
phenomenologically, to schizophrenia but combines schizophrenic symptoms with affective symptoms. The criteria are discussed in Chapter 4.3.9. Schizophreniform (DSM-IV) or acute schizophrenia-like disorders (ICD-10) differ only in terms of duration, as operationally deﬁ  ned (see Chapter 4.3.10). Delusional disorders 
(Chapter 4.4) differ from schizophrenia in being based around‘non-bizarre’ delusions and few or no hallucinations. The onset and course are characteristically later and more benign respectively.
(b) Affective disorders
Typical presentations of either mania or depression usually cause few diagnostic difﬁ  culties. Overdiagnosis of schizoaffective disor-

der is to be resisted although the distinction from schizophrenia proper remains controversial and debatable. The guidelines given in DSM-IV attempt to exclude transient mood disturbances (<2 weeks) in people with psychosis as a basis for a schizoaffective diagnosis.
In practice reaching a diagnosis of schizophrenia in a person 
with evidence of one or more core symptoms of psychosis (listed under the DSM-IV and ICD-10) may be complicated for the following reasons.
(c)  The presence of mood-incongruent delusions 
(or hallucinations)
‘Congruence’ is somewhat in the eye of the beholder, especially

‘Congruence’ is somewhat in the eye of the beholder, especially 
where mood may be labile or where disturbed mood is suspected but fails to follow clinical stereotypes. The clinician should try to determine if a ‘grandiose’ delusion is being enjoyed by the patient, and whether the content (e.g. elevated status, magical powers, material riches) is seen as justiﬁ  ed by the patient. Similarly a delu-
sion of depressive content (e.g. physical illness, imminent death) must be seen as undeserved or inexplicable to be deemed ‘incongruent’ . Auditory hallucinations may be comforting, compli-mentary, or, more commonly, hostile and critical. It is probably their complexity and personiﬁ  cation which makes them ‘schizo-
phrenic’ rather than their mood-incongruent content.
(d) The duration and acuteness of onset criteria

A good history may simply not be available. Symptoms may wax and wane. Partial or successful treatment may modify or curtail a potentially long episode, and onset may be complicated by the use of psychoactive drugs.
(e) Social and occupational disturbance
This is critical to the diagnosis of schizophrenia, especially the DSM-IV criteria. Here the difﬁ  culty is in distinguishing ‘premorbid 
deﬁ cits’ , an illness prodrome and the illness itself. Premorbid

deﬁ cits’ , an illness prodrome and the illness itself. Premorbid 
personality factors will obscure or set in relief discontinuities in an individual’s social trajectory. Objective information and informant testimony is crucial as in most of the diagnostic process. Other individual differences such as intelligence will also shape the pre-sentation of schizophrenia. At the extreme, people with intellectual disability (learning disability) may manifest psychosis in less obvious ways (see Chapters 10.5.1 to 10.5.3). The old diagnosis of ‘simple schizophrenia’ , retained in the ICD-10 describes ‘insidious and progressive development of oddities of conduct’ and the 
‘inability to meet the demands of society’ that is, social disturbance of long duration. The progressive element distinguishes it from personality disorder although problems adjusting to changing social demands through the life cycle may give the appearance of progression in a ﬁ  xed personality disorder.
Organic conditions

Differentiation of a ‘primary’ psychotic illness from one secondary 
to an organic condition may arise in essentially two situations:
X a person with a clear-cut diagnosis of a medical or neurological 
syndrome in which psychosis is a recognized complication (e.g. epilepsy)
X a person with a presumptive diagnosis of schizophrenia in whom 
signiﬁ  cant abnormalities are detected usually following special 
investigation (e.g. CT brain scanning).
The list of medical conditions that could potentially give rise to 
psychosis is enormous. These have been the subject of extensive reviews.
(22, 23) While it appears that almost any disease that causes a 
cerebral perturbation can give rise to psychosis, abnormalities affecting the temporal lobes and diencephalon are somewhat more likely to do this.
The time course is obviously important in this context. Chronic 
inﬂ ammatory lesions (e.g. sarcoidosis), degenerative disorders (e.g.

inﬂ ammatory lesions (e.g. sarcoidosis), degenerative disorders (e.g. 
presenile dementias), chronic infections (e.g. neurosyphilis, AIDS), space-occupying lesions (e.g. tumour or abscesses), metabolic dis-orders (e.g. hyper- or hypothyroidism and vitamin deﬁ  ciencies)

may mimic schizophrenia by virtue of a gradual deterioration in social functioning and self-care punctuated perhaps by odd or inexplicable behaviour and rarely hallucinations and delusions. The features of the primary disease are usually evident. Rarer conditions may be misdiagnosed, for example, Wilson’s disease (hepatolenticular degeneration). This usually presents with a motor disorder with bulbar features and abnormal liver function, but personality changes and psychotic symptoms are also associated. Diagnosis is made on other associated clinical features (e.g. Kayser–Fleischer rings), copper studies, and liver biopsy. Huntington’s disease is characterized by chorea and cognitive decline. Affective disorder and occasionally psychotic symptoms may occur. The main differential diagnosis is with patients with chronic psychosis and tardive dyskinesia and is usually clariﬁ  ed by the family history,

inexorable progression, and caudate atrophy on CT or MRI. Neurosyphilis is still encountered from time to time and in the ‘general paralysis of the insane’ form, may present with chronic delusions (often grandiose) plus dementia. Diagnosis is by appro-priate serological testing of blood and cerebrospinal ﬂ  uid. Finally, 
metachromatic leukodystrophy, a rare inherited progressive demy-elinating condition, has recently been identiﬁ  ed as a cause of a 
schizophrenia-like psychosis, when onset is in childhood or early adult life.
(24) Arylsulphatase-A is a diagnostic marker detectable in 
peripheral white blood cells.
Acute disturbances following head trauma, acute infections (viral

Acute disturbances following head trauma, acute infections (viral 
encephalitis), cerebrovascular accidents, metabolic abnormalities (e.g. electrolyte disturbances, porphyria), or drug intoxication or withdrawal (including prescribed medication) (see below) may present with a florid psychotic picture, classically dominatedby visual distortions or hallucinations and ﬂ  uctuating levels of 4.3.4 diagnosis, classification, and differential diagnosis of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 538
alertness, rather than the stereotyped auditory hallucinations in 
clear consciousness which are characteristic of schizophrenia.(25)
In practice there are few common conditions that ever give rise 
to real diagnostic uncertainty. The most important is epilepsy . It is 
well established that epilepsy, particularly focal (complex partial 
or ‘temporal lobe epilepsy’) can give rise to psychosis and there are inter-ictal and post-ictal patterns (see Chapter 5.3.3). A survey from a large neurology clinic showed that the incidence of schizo-phrenia is about nine times that of the rest of the population.
(26)
Inter-ictal psychoses include the chronic schizophrenia-like 
psychoses described by Slater et al .(27) and Trimble.(28) These

(26)
psychoses described by Slater et al .(27) and Trimble.(28) These 
almost always arise in people with many years of well-established temporal lobe seizures, while the post-ictal variety occurs earlier in the life cycle but again in a person with previously diagnosed epi-lepsy. In post-ictal psychosis the temporal relationship to seizures, sometimes occurring in a cluster, is diagnostic, although a lucid interval is often observed. A clear history and independent descrip-tion of seizures is the foundation of a diagnosis of epilepsy, with EEG conﬁ  rmation. Resting EEGs show slight and subtle abnormal-
ities in a substantial minority of patients with schizophrenia which may be accentuated by antipsychotic medication. As such, the EEG may be of limited value in differential diagnosis unless pronounced slowing or frank seizure activity is picked up (see also Chapter 5.3.3.).
(a) Symptoms

Symptoms of schizophrenic psychosis in relative isolation may give rise to diagnostic difﬁ  culties.
Auditory hallucinations may occur in alcoholic hallucinosis (see 
below and Chapter 4.2.2.3). Hallucinations in the context of disso-ciation (voices representing ﬁ  gures from the patient’s past or 
embodiments of aspects of their personality) must also be distin-guished from typical schizophrenic hallucinations. These are often multimodal. Pure auditory hallucinations in organic conditions including epilepsy in the absence of other psychotic features are surprisingly rare.
Certain forms of delusion suggest alternative diagnoses. Transient 
ill-formed but usually paranoid delusions occur in the context of confusion, memory impairment, or dementia (i.e. things going missing, strange people loitering). Delusions of misidentiﬁ  cation 
are particularly associated with organic illness such as dementia or stroke.
Thought disorder may be confused with a ﬂ  uent aphasia follow-

ing stroke or cerebral tumours.
Personality deterioration and inappropriate or disinhibited 
behaviour can occur in many organic conditions in the absence of overt psychotic features. Isolated frontal lesions may cause diag-nostic problems since general cognitive impairments may be absent. The widespread availability of CT and MRI in the more developed world has reduced the likelihood of such patients being misdiagnosed.
A small proportion (approximately 5 per cent) of prevalent 
and incident cases of schizophrenia, if investigated thoroughly, are found to have a variety of ‘organic’ conditions which may contrib-ute to the illness.
(29) These include metabolic abnormalities,

(29) These include metabolic abnormalities, 
cerebral tumours, multisystem autoimmune disease, cerebrovascu-lar disease, etc. Some of these may be incidental; others may have precipitated the psychosis. The range of diseases counts against any speciﬁ  c aetiological mechanism. Similarly, the phenomenology found in such ‘organic’ patients is usually indistinguishable from 
their ‘functional’ counterparts.
(30)
Thanks to increased application of non-invasive neuroimaging 
techniques to psychiatric patients, particularly those with schizo-
phrenia, another class of organic abnormalities have been noted, namely cerebral anomalies which are often congenital. These include agenesis of the corpus callosum, cavum septum pellucidum, aque-duct stenosis, etc. Again, it is difﬁ  cult to know how often such

ﬁ ndings occur in the normal population and are asymptomatic, 
although the widespread use of MRI for ‘minor’ complaints such as mild head injury and headache is uncovering such anomalies. The examples above certainly appear to be associated with psychiatric disorders in general more than would be expected by chance. They tend to be associated with below-average IQ and other neurological problems (epilepsy in the cases of callosal agenesis).
Other factors to be taken into account in the differential diagno-

sis from organic conditions include the presence of a family history of schizophrenia, and abnormal premorbid personality, bothof which weight aetiological judgement in favour of the functional diagnosis. This applies to the psychoses of epilepsy and thoserelated to drug abuse especially. ‘Secondary’ schizophrenias also tend to have less pervasive effects on the person’s personality. Treatment is again based on symptoms with the added complica-tion that antipsychotic drugs lower the epileptic seizure threshold, and will tend to worsen extrapyramidal symptoms in patientswith primary movement disorders. Treatment of the primarycondition (if this has remained undiagnosed for some time) may be disappointing but should always be attempted especially in the case of chronic infections. Reversal of metabolic abnormalities,
even long-standing, can lead to dramatic improvements in the 
mental state.
(b) Drug-induced psychoses

Many drugs of abuse and prescribed drugs can cause psychotic 
symptoms. The associations are also considered in Chapters 4.2.3.1 to 4.2.3.9. In the context of a differential diagnosis, drugs of abuse—in adolescents and young adults—must be considered. Chronic amphetamine psychosis may be indistinguishable from schizophrenia. The psychosis is ﬂ  orid and may include visual and 
auditory hallucinations. Phencyclidine (PCP or angel dust) is a drug of abuse in the United States and causes an acute psychosis with prominent affective symptoms as well as perceptual distor-tions and depersonalization. Other psychotogenic drugs include cocaine, ecstasy, and Lysergic Acid Diethylamide(LSD).
Cannabis is widely used, especially in large metropolitan areas 
and by certain ethnic groups (e.g. African-Caribbeans). Cannabis intoxication is more characterized by perceptual distortions and

and by certain ethnic groups (e.g. African-Caribbeans). Cannabis intoxication is more characterized by perceptual distortions and 
depersonalization than frank psychosis. Clinical experience suggests 
that cannabis has a propensity to precipitate psychotic relapse in patients with established schizophrenia and a recent meta-analysis of cohort studies concludes that cannabis use is certainly a risk factor for schizophrenia, and other psychiatric disorders.
(31)
Delusions and hallucinations may occur rarely during states 
of alcohol intoxication but are more commonly associated with withdrawal syndromes (Chapter 4.2.2.2). Alcoholic hallucinosis is a chronic hallucinatory state of uncertain nosological status in which the patient with long-standing alcohol dependence often hears ‘voices’ which may be derogatory and commenting, in clear consciousness, after a lengthy withdrawal period.

539
(c) Prescribed medication
Again the list of agents that can cause psychotic reactions to be 
distinguished from schizophrenia is very long, and psychotropic drugs are particularly liable to cause psychotic reactions. Two classes of drug deserve mention because of their widespread use and rela-tively high incidence of major psychiatric adverse effects:
X steroids can cause a wide range of psychiatric disturbances 
including psychosis
X dopamine agonists used in the treatment of Parkinson’s disease 
and some pituitary adenomas.
Frank psychosis and affective disorders may be seen. In the
treatment of neurological diseases, such as Parkinson’s disease,and the use of steroids for diseases of the central nervous system, there is often an interaction between the agent and the underlying condition which increases the likelihood of a drug-inducedpsychosis.
The diagnostic process

It used to be argued that a diagnosis of schizophrenia in itself caused disability and morbidity due to social ‘labelling’ and stigma-tization. Evidence that this accounts for schizophrenic disability is lacking but the reality of the stigma of mental illness and negative attitudes towards ‘schizophrenics’ cannot be denied. This is espe-cially delicate in the case of early intervention with people present-ing without the full-blown schizophrenic syndrome since arguably, the balance of harms and beneﬁ  ts of diagnosis is tilted slightly away 
from beneﬁ  t. Hence, making a diagnosis of schizophrenia should 
not be taken lightly. In the author’s experience, very few psychia-trists spontaneously convey the diagnosis to the patient. If a patient asks whether he or she has schizophrenia, the clinician should ﬁ  rst

try to understand the motivation behind the question and the patient’s knowledge and understanding of the term. Ultimately there is seldom justiﬁ  cation in withholding the diagnosis if it is 
established. A schizophrenia diagnosis can be framed in a relatively positive light—this is a condition which we are now beginning to understand and for which there are effective treatments—and may lessen the burden of responsibility and blame that the patient and his or her family may carry for the disorder.
McKenna, P .J. (2007). Schizophrenia and related syndromes  (2nd edn). 
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SECTION 4  clinical syndromes of adult psychiatry 540
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4.3.5 Epidemiology of 

Epidemiological research into schizophrenia aims to answer four 
essential questions.
X What is the ‘true’ population frequency of the disorder in various 
populations and how is it distributed across the various groups within populations?
X Do the incidence, manifestations, and course of schizophrenia 
vary in relation to factors of the physical and social environment?
X Who is at risk and what forces determine or inﬂ  uence the risk of 
developing schizophrenia?X Can the answers to the above questions help explain what causes 
the disorder and how to prevent it?
The hallmark of the epidemiological method (see Chapter 2.7) 
is the referral of a measure (numerator) of the occurrence of a dis-order, or of any associated characteristics, to a population base

is the referral of a measure (numerator) of the occurrence of a dis-order, or of any associated characteristics, to a population base 
(denominator), such as person-years at risk . The epidemiological 
study of diseases usually proceeds from a description of its freque ncy 
and associations (establishing rates of occurrence) to testing hypo-theses about risk factors and causes by analysing ratios between rates.
Schizophrenia has been studied extensively from an epidemio-
logical perspective since Kraepelin
(1) introduced the concept of 
dementia praecox  in 1896. In the ﬁ  rst half of the twentieth century,

dementia praecox  in 1896. In the ﬁ  rst half of the twentieth century, 
epidemiological research into schizophrenia took two divergent paths. While European studies tended to focus on population dis-tributions and genetic risks, North American researchers investi-gated the social ecology of the disorder. A variety of methods were explored and successfully applied by the pioneers of psychiatric epidemiology, and the contours of the epidemiological map of schizophrenia in Europe and North America were effectively laid down between the two World Wars. The early studies were carried out by dedicated researchers who often spent months or years col-lecting data ‘door-to-door’ in small communities. Close knowledge of the respondents, access to multigenerational records from the local parish registers, and the cooperation of the community result-ed in studies that remain landmarks of psychiatric epidemiology 
(Table 4.3.5.1).

During the last several decades, the scope of epidemiological 
studies of schizophrenia has expanded to include populations in Asia, Africa, and South America about which little had been known previously. The World Health Organization ( WHO ) International 
Pilot Study of Schizophrenia and its successor, the WHO 10-country epidemiological study
(9,10)  were the ﬁ  rst systematic investigations 
of the comparative incidence, clinical manifestations, and course 
Table 4.3.5.1  Historical landmarks in the epidemiology of psychoses
Author Method Target population Case-ﬁ  nding Assessment
Koller (1895)(2)The ﬁ  rst epidemiological case-
 control study of psychosesProbands with psychoses ( n = 287) and 
 non-psychiatric controls ( n = 370)Records of psychiatric hospitals 
 and clinicsGenealogical inquiry
Luxenburger (1928)(3) Twin concordance/discordance 
 analysis; sampling designMonozygotic and dizygotic twin pairs Census of inpatients; search of

and clinicsGenealogical inquiry
 analysis; sampling designMonozygotic and dizygotic twin pairs Census of inpatients; search of 
 birth registers for twin birthsEmphasis on reliability of 
  diagnosis: ‘deﬁ  nite’ and 
‘probable’
Brugger (1931)(4) Census (door-to-door survey) Area in Thuringia, population 37 561 Records and key informants 
  consulted to detect ‘suspected’ 
casesPersonal examination of 
  ‘suspected’ cases and of a 
control sample
Klemperer (1933)(5)Birth cohort study Random sample ( n = 1000) from all 
 births in Munich, 1881–90Attempted tracing of all cohort 
  members, 44% successfully 
tracedPersonal examination or 
  key informant interview 
(271 examined)
Ödegaard (1946)(6) Cumulative national case register Entire population of Norway Registration of all ﬁ  rst-
  admissions 1926–35 
(n = 14 231)Statistical analysis of 
  hospital diagnoses and 
records
Essen-Möller et al. 
  (1956);(7) Hagnell

admissions 1926–35 
records
  (1956);(7) Hagnell 
(1966)(8)Census followed by repeated  follow-up surveysRural community, initial population 
  2550 (+1013 new residents in the 
course of follow-up)Complete census; tracing 
 of migrantsPersonal examination 
  (and re-examination) of 
all residents

541
of schizophrenia in both developing and developed countries. The 
WHO programme was an impetus for similar studies in India, China, the Caribbean, and Australia. Two major studies of psychi-atric morbidity in the United States, the Epidemiological Catchment Area project,
(11) and the National Comorbidity Survey,(12) gener-
ated data on the prevalence of DSM-III/IIIR schizophrenia and related disorders in representative population samples. In the 1980s and 1990s, epidemiological studies increasingly utilized existing large databases such as cumulative case registers or birth cohorts to test hypotheses about risk factors, and began to include methods of genetic epidemiology. There is a current tendency towards integrating epidemiological approaches with other types of aetio-logical research in schizophrenia. This predicts an important role for epidemiology in the era of molecular biology of mental disorders.
Epidemiological methods and instruments 
in the study of schizophrenia

The measurement of the prevalence, incidence, and disease expec-
tancy of schizophrenia depends critically on the sensitivity of the case-ﬁ  nding method (i.e. its capacity to identify all affected persons 
in a given population) and the availability of a diagnostic instru-ment or procedure that selects ‘true’ cases (i.e. those corresponding to an established clinical concept).
Case-ﬁ  nding
Case-ﬁ  nding designs fall into three broad groups: case detection in 
clinical populations, door-to-door surveys of population samples or whole communities, and birth cohort studies. Each method has its advantages and limitations.
While case-ﬁ  nding through the mental health services provides a 
relatively easy access to a substantial proportion of all persons with schizophrenia, the cases in treatment  may not be fully representa-

tive of all individuals with the disorder. Bias related to gender, marital status, socio-economic factors, culture, or ethnicity are known to affect the probability of being in treatment at a given time in a given setting, and generalizations about schizophrenia from hospital or clinic samples are liable to error. Some of the deﬁ  -
ciencies of case-ﬁ  nding through service contacts are avoided in 
cumulative national or regional psychiatric case registers, which 
cover large well-deﬁ  ned populations and can be linked to other 
population databases (e.g. birth records). This makes registers efﬁ cient research instruments in low-incidence disorders such as 
Surveys  involve accounting for every person at risk within a 
deﬁ ned community or a population sample in terms of either being

deﬁ ned community or a population sample in terms of either being 
or not being a case. Face-to-face interviews (and follow-up) of all residents in deﬁ  ned communities has been a feature of some high-
quality research, especially in the Scandinavian countries. However, since the size of the populations surveyed in this way is limited, the number of detected cases of schizophrenia is usually too small to generate stable estimates of epidemiological parameters. Surveys of large populations involve two basic designs: a single-phase survey of a probability sample drawn from the general population, and a two-phase survey where a validated screening test is ﬁ  rst applied 
to the entire population and only those scoring as screen-positive proceed to a full assessment. In the instance of schizophrenia, logistics dictates a choice between assessing large numbers less

to the entire population and only those scoring as screen-positive proceed to a full assessment. In the instance of schizophrenia, logistics dictates a choice between assessing large numbers less 
rigorously and investigating a smaller sample in greater depth. In the absence of a simple and valid screening procedure for schizo-phrenia, such as a biological or psychological test, the advantages of the two-phase survey may be offset by poor sensitivity or speciﬁ  city of the screening device which is usually a questionnaire 
or checklist.
The study of birth cohorts  at ages when their members have

The study of birth cohorts  at ages when their members have 
passed through the greater part of the period of risk for onset of schizophrenia is usually done by direct interviewing or by analys-ing available case register data. Well-characterized birth cohorts are among the best tools for the study of the incidence of schizo-phrenia and associated risk factors. However, even in settings where the population is stable and mortality and morbidity are adequately monitored, the size of birth cohorts with prospectively collected data may not be sufficient for conclusive epidemiological inferences.
All this suggests that there is no single ‘gold standard’ of case-
ﬁ nding for schizophrenia that could be applied across all possible 
settings, and the assets and liabilities of particular case-ﬁ  nding

settings, and the assets and liabilities of particular case-ﬁ  nding 
procedures need to be evaluated in the context of each study. This makes the detailed reporting of case-finding methods a mandatory prerequisite for an ‘evidence-based’ epidemiology of schizophrenia.
Diagnosis
Variation in diagnostic concepts and practices always explains a proportion of the variation in the results of schizophrenia studies, especially if they involve different populations or different periods. Until the 1960s, the diagnostic rules used in epidemiological research were seldom explicitly stated. In the late 1960s, the WHO International Pilot Study of Schizophrenia
(10) examined diagnostic 
variation in schizophrenia across nine countries by comparing the diagnoses made by psychiatrists using a semi-structured clinical interview with diagnostic classiﬁ  cation by a computer algorithm
(13)

(13)
utilizing the same interview data. The results demonstrated that 
in the majority of settings psychiatrists were using comparable diagnostic concepts in the Kraepelin–Bleuler tradition. The intro-duction of explicit diagnostic criteria and rules with the consecu-tive editions of DSM  and the WHO’s ICD-10  improved further 
the reliability of diagnosis but did not resolve all diagnostic issues with implications for epidemiology. While ICD-10 and DSM-IV tend to agree well on the core cases of schizophrenia, they agree less well on the classiﬁ  cation of atypical or milder cases. Such dif-
ferences may be less important in clinical practice but they present a problem for epidemiological and genetic studies. By providing more restrictive criteria for schizophrenia, both classiﬁ  cations aim 
to identify clinically similar cases and to minimize false-positive diagnoses. This is not an unequivocal advantage for epidemiology.

to identify clinically similar cases and to minimize false-positive diagnoses. This is not an unequivocal advantage for epidemiology. 
Applying such criteria at case-ﬁ  nding may result in the rejection of 
potential cases which fail to meet the full set of criteria at initial assessment. Therefore it is desirable to develop less restrictive screening versions of the DSM and ICD criteria for epidemiologi-cal research.
Instruments
The diagnostic instruments used in surveys which involve inter-viewing fall into two categories: fully structured interviews such as 4.3.5 epidemiology of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 542
the Diagnostic Interview Schedule ( DIS)(12) and the Composite 
International Diagnostic Interview ( CIDI )(14) both written to 
match exactly the diagnostic criteria of DSM-IIIR/IV and ICD-10, and semi-structured interview schedules such as the Present State Examination ( PSE)
(13) and the Schedules for Clinical Assessment 
in Neuropsychiatry ( SCAN ),(15) which cover a broad range of psy-
chopathology and elicit data that can be processed by alternative diagnostic algorithms.
The DIS/CIDI type of instrument is reliable and capable of 
generating standard diagnoses of common mental disorders in a single-phase survey design. Its clinical validity in schizophrenia is less certain because symptoms may not be reported accurately or impairment may be underestimated by the respondent. In contrast, the PSE/SCAN allows a greater amount of psychopathological data to be elicited in a ﬂ  exible clinical interview format, but its use in

epidemiological studies presupposes availability of clinically trained interviewers. While SCAN and other similar interviews are suitable as second-stage diagnostic instruments, there is still a need for a relatively simple and effective screening procedure for case-
ﬁ nding of schizophrenia in ﬁ  eld surveys.
Persons, place, time: descriptive 
epidemiology of schizophrenia
The epidemiological description of schizophrenia draws on 
extensive evidence available today on its frequency, age, and sex distribution in relatively large populations or geographical areas. Less than complete information is available on variations in its epidemiological characteristics that may be found in unusual or isolated populations, or on the temporal trends in its occurrence.
Prevalence, incidence, and disease expectancy
(a) Prevalence

Prevalence provides an estimate of the number of cases per 1000 persons at risk present in a population at a given time or over a deﬁ ned period. Point prevalence  refers to the ‘active’ (i.e. symp-
tomatic) cases on a given date, or within a brief census period. Since asymptomatic cases (e.g. persons in remission) will be missed in a point prevalence survey, it is useful to supplement the assess-ment of the present mental state with an enquiry about past episodes of the disorder to obtain a lifetime prevalence  index. 
In schizophrenia, which tends to a chronic course, estimates of point and lifetime prevalence will be closer to each other than in remitting illnesses.
An overview of selected prevalence studies of schizophrenia 
spanning nearly seven decades is presented in Table 4.3.5.2. The studies differ in many aspects of methodology but the majority of

spanning nearly seven decades is presented in Table 4.3.5.2. The studies differ in many aspects of methodology but the majority of 
them feature a high intensity of case-ﬁ  nding. Several studies are 
repeat surveys in which the original population was reinvestigated following an interval of 10 or more years (the resulting consecutive prevalence ﬁ  gures are indicated by arrows).
The majority of studies have produced point prevalence esti-
mates in the range 2.1 to 7.0 per 1000 population at risk and life-time prevalence of schizophrenia in the range 15.0 to 19.0 per 1000. The ﬁ  gures are not uniformly standardized, and should be com-
pared with caution because of demographic differences between populations related to factors such as age-speciﬁ  c mortality and 
migration. A systematic review  of 188 studies in 46 countries, published between 1965 and 2002,
(16) estimated the median value

(16) estimated the median value 
for point prevalence at 4.6 per 1000 persons and for lifetime preva-lence at 7.2 per 1000.
Certain populations and groups deviate markedly from the 
central tendency. Strikingly high prevalence of schizophrenia (two to three times the national or regional average) has been found in geographically and genetically isolated populations , including 
small communities in Northern Sweden and Finland, and several Western Paciﬁ  c islands (see Table 4.3.5.2). At the other extreme, a 
virtual absence of schizophrenia and a high rate of depression have been claimed for the Hutterites of South Dakota, a Protestant sect whose members live in close-knit endogamous communities 
sheltered from the outside world.
(33) Negative social selection for

(33) Negative social selection for 
schizoid individuals who fail to adjust to the lifestyle of the major-ity and eventually migrate without leaving progeny has been suggested (but not deﬁ  nitively proven) as an explanation. Results 
of two surveys in Taiwan,
(21) separated by 15 years, point to a fall-
ing prevalence of schizophrenia (from 2.1 to 1.4 per 1000) in the context of major socio-economic change and an overall increase in total mental morbidity in the population.
The question about the extent of true variation in the prevalence 
of schizophrenia across populations has no simple answer. Methodological differences among studies, related to sampling, case-ﬁ  nding, and diagnostic assessment are likely to account for a 
good deal of the observed variation. As an example, the high mean prevalence rate of DSM-III schizophrenia reported from the Epidemiologic Catchment Area study in the United States
(25) is

(25) is 
difﬁ cult to reconcile with inconsistencies, such as a 13-fold differ-
ence in the rates for age group 18–24 years across the various sites of the survey. One possible reason is that the principal diagnostic instrument of the survey (DIS), administered by lay interviewers, may produce both false-positive and false-negative diagnoses of schizophrenia in a number of cases. Similarly, computer-generated diagnoses of ‘non-affective psychosis’ in the National Comorbidity Survey,
(12) based on a version of the CIDI administered by lay 
interviewers, were found to agree poorly with clinicians’ diagnoses when a subsample of the respondents were re-interviewed over the telephone.
(34)
Notwithstanding such caveats in the interpretation of survey

(34)
Notwithstanding such caveats in the interpretation of survey 
ﬁ ndings, the prevalence rates are fairly similar in the majority of 
studies, though certain speciﬁ  c populations clearly deviate from 
the modal value. Even in those instances, however, the magnitude of the deviation is modest compared with the 10- to 30-fold dif-ferences in prevalence observed in other multifactorial diseases (e.g. diabetes, ischaemic heart disease, multiple sclerosis) across populations.
(b) Incidence
The incidence rate (an estimate of the annual number of ﬁ  rst-onset 
cases in a deﬁ  ned population per 1000 persons at risk) is of greater

cases in a deﬁ  ned population per 1000 persons at risk) is of greater 
interest for the study of risk factors than prevalence since it representsthe so-called force of morbidity (the probability of disease occur-rence) in a given population, and is closer in time to the action of antecedent or precipitating factors. The estimation of incidence depends critically on the ability to determine reliably the point of onset  of the disorder. In the case of schizophrenia, the long prodro-
mal period and the fuzzy boundary between premorbid state and onset of psychosis make this particularly difﬁ  cult. In the absence of 
an objective biomarker of the disease, onset is usually deﬁ  ned as

543
the point in time when clinical manifestations become recogniz-
able and diagnosable according to speciﬁ  ed criteria. The ﬁ  rst 
hospital admission, which has been used as a proxy for disease onset in many studies, is not a robust indicator because of the vari-able time lag between the earliest appearance of symptoms and the ﬁ rst-admission across treatment facilities and settings. A better 
approximation is provided by the ﬁ  rst-contact, i.e. the point at 
which any psychiatric, general medical, or alternative ‘helping’ agency is accessed by symptomatic individuals for the ﬁ  rst time. 
A limitation common to both ﬁ  rst-admission and ﬁ  rst-contact 
studies is that they produce rates of ‘treated’ incidence and miss symptomatic cases that do not present for assessment or treatment. This limitation can be overcome by periodically repeated door-to-door surveys of the same population or by longitudinal cohort 
studies (though both are difﬁ  cult to mount for reasons of cost and

studies (though both are difﬁ  cult to mount for reasons of cost and 
logistics).Table 4.3.5.3 summarizes the essential features of 12 selected 
incidence studies of schizophrenia. Studies using a ‘broad’ deﬁ  ni-
tion of schizophrenia (ICD-8 or ICD-9) estimate about three-fold difference in the variation of rates, in the range from 0.17 to 0.57 per 1000 population per year, for ﬁ  rst-admissions or ﬁ  rst contacts. 
Studies using more stringent criteria, such as the Research Diagnostic Criteria ( RDC ),
(121) DSM-IV , ICD-10, or Catego S+ ,(13)
have reported incidence rates two to three times lower than those 
based on ‘broad’ criteria. A systematic review  of data from some 
160 studies from 33 countries, published between 1965 and 2001,
(35) yielded a median value of 0.15 and mean value of 0.24 per 
1000, with a ﬁ  ve-fold range of the rates and a tendency for more 
recent studies to report lower rates.
Considering the methodological differences among individual

Considering the methodological differences among individual 
studies, generalizing about the incidence of schizophrenia from pooled data may be problematic. T o date, the only investigation Table 4.3.5.2  Selected prevalence studies of schizophrenia
Author Country Population Method Prevalence per 1000 
population at risk
Brugger (1931)(4) Germany Area in Thuringia ( n =37 561); age 10+ Census; interview of sample 2.4
Strömgren (1938)(17); 
  Bøjholm and Strömgren 
(1989)(18)Denmark Island population ( n = 50 000) Census interviews; repeat census 3.9→3..3
Böök (1953);(19) Böök 
 et al. (1978)(20)Sweden Genetic isolate ( n = 9000); age 15–50 Census interviews; repeat census 9.5→17.0
Essen-Möller et al. (1956);(7) 
 Hagnell (1966)(8)Sweden Community in Southern Sweden Census interviews; repeat census 6.7→4.5

Lin et al. (1989)(21)Taiwan Population sample Census interviews; repeat census 2.1→1.4
Crocetti et al. (1971)(22) Croatia Sample of 9201 households Census based on hospital records and 
 interviews5.9
Dube and Kumar (1972)(23)India Four areas in Agra ( n = 29 468) Census based on hospital and clinic records 2.6
Rotstein (1977)(24)Russia Population sample ( n = 35 590) Census based on hospital and clinic records 3.8
Keith et al.  (1991)(25)USA Aggregated data across ﬁ  ve ECA sites Sample survey; interviews 7.0 (point) 
15.0 (lifetime)
Jeffreys et al.  (1997)(26) UK London health district ( n = 112 127) Census; interview of sample ( n = 172) 5.1
Kebede et al.  (1999)(27) Ethiopia 25 districts of Addis Ababa 
 (n = 2 228 490)Screening by self-report questionnaire, 
 interviews of sample ( n = 2042)7.0 (point) 
9.0 (lifetime)

Jablensky et al.  (2000)(28)Australia Four urban areas ( n = 1 084 978) Census, screen for psychosis; interviews of 
 sample ( n = 980)3.1–5.9 (point)a 3.9–6.9 
(period, one year)b
Waldo et al.  (1999)(29) Micronesia Island of Kosrae Genetic isolate Screen of hospital records, interviews 6.8 (point)
Arajärvi et al.  (2005)(30) Finland Birth cohort ( n = 14 817) Genetic isolate Case register data; interviews of 55% of 
 register cases15.0 (lifetime) 
19.0c (lifetime)
Wu et al. (2006)(31)USA 
(California)Medicaid/Medicare health 
 insurance data20% random sample of insured subjects 5.1 (period, 1 year)
Perälä et al. (2007)(32)Finland National sample ( n = 8028) Screen for psychosis, interviews of sample; 
 register and case note data also used10.0 (lifetime) 
22.9d (lifetime)
aAll psychoses.

bSchizophrenia and other non-affective psychotic disorders.
cSchizophrenia spectrum disorders.
dNon-affective psychotic disorders.4.3.5 epidemiology of schizophrenia

544
that has applied a uniform design and common research tools to 
generate directly comparable incidence data for different popula-tions is the WHO 10-country study .
(9) Incidence counts in the 
WHO study were based on ﬁ  rst-in-lifetime contacts with any 
‘helping agency’ within deﬁ  ned areas (including traditional healers 
in the developing countries) which were monitored over a 2-year period. Potential cases and key informants were interviewed by clinicians using standardized instruments, and the timing of onset was ascertained for the majority of the patients. In 86 per cent of the 1022 patients the onset of diagnostic symptoms of schizophre-nia was within the year preceding the ﬁ  rst-contact, and therefore 
the ﬁ  rst-contact incidence rate was adopted as a reasonable approx-
imation to the ‘true’ onset rate. Two deﬁ  nitions of ‘caseness’ , dif-
fering in the degree of speciﬁ  city, were used to determine incidence:

fering in the degree of speciﬁ  city, were used to determine incidence: 
a ‘broad’ clinical definition comprising ICD-9 schizophrenia and paranoid psychoses, and a more restrictive deﬁ  nition of PSE/
Catego S+
(13) ‘nuclear’ schizophrenia manifesting with Schneiderian 
ﬁ rst-rank symptoms . The rates for eight of the catchment areas 
are shown in Table 4.3.5.4.
The differences between the area rates for ‘broadly’ deﬁ  ned 
schizophrenia (0.16–0.42 per 1000) were signiﬁ  cant ( p < 0.001) but 
those for ‘nuclear’ schizophrenia were not, suggesting that the frequency of this diagnostic subgroup varies less across different populations. No differences were found between cases meeting only ‘broad’ ICD-9 criteria and the Catego S+ cases with regard to age at onset, or 2-year course and outcome. Therefore it is unlikely that ‘nuclear’ and ‘broad’ schizophrenia deﬁ  ne two different clinical

illnesses.Replications of the design of the WHO 10-country study, includ-
ing its research procedures and instruments, have been carried out with very similar results in India, the Caribbean, and the United Kingdom (Table 4.3.5.3).
(c) Disease expectancy (morbid risk)
This is the probability (expressed as a percentage) that an individu-al born into a particular population will develop the disease if he or she survives the period of risk for that disease. In the instance of schizophrenia the period of risk  is usually deﬁ  ned as 15 to 54 years. 
If age- and sex-speciﬁ  c incidence rates are known, disease expec-
tancy can be estimated directly by a summation of the age-speciﬁ  c 
rates within the period of risk. Alternatively, disease expectancy can be estimated indirectly from prevalence data.
The estimates of disease expectancy produced by a number 
of studies are fairly consistent across populations and over time. Excluding outliers, such as the northern Swedish isolate,

(19,20)  they 
vary about ﬁ  ve-fold; in the WHO study, they range from 0.59 per cent 
(Aarhus) to 1.8 per cent (Chandigarh, rural area) for ICD-9 schizo-phrenia and from 0.26 per cent (Honolulu) to 0.54 per cent (Nottingham) for Catego S+ ‘nuclear’ schizophrenia. The frequently cited modal estimate of lifetime disease expectancy for broadly deﬁ ned schizophrenia at around 1 per cent seems to be consistent 
with the evidence.
(d) Associations with age and sex
Schizophrenia may have its onset at any age—in childhood as well as past middle age—although the vast majority of onsets fall within the 15 to 54 years of age interval. Onsets in men peak steeply in the SECTION 4  clinical syndromes of adult psychiatry
Table 4.3.5.3  Selected incidence studies of schizophrenia

Author Country Population Method Rate per 1000
Ödegaard (1946)(6) Norway Total population First-admissions 1926–35 ( n = 14 231) 0.24 (Hospital diagnoses)
Walsh (1969)(36) Ireland City of Dublin ( n = 720 000) First-admissions 0.57 (males, ICD-8); 0.46 
 (females, ICD-8)
Murphy and Raman 
 (1971)(37)Mauritius Total population ( n = 257 000) First-admissions 0.24 (Africans); 0.14 
  (Indian Hindus); 0.09
(Indian Moslems)
Lieberman (1974)(38) Russia Moscow district ( n = 248 000) Follow-back of prevalent cases 0.20 (males)
0.19 (females)
Helgason (1977)(39)Iceland Total population First-admissions (case register) 0.27 (ICD-8)
Lin et al. (1989)(21)Taiwan Three communities ( n = 39 024) Door-to-door survey 0.17 (‘Bleulerian’ criteria)
Castle et al. (1991)(40)UK London (Camberwell) First-admissions (case register) 0.25 (ICD-9); 0.17 (RDC); 
 0.08 (DSM-III)

Rajkumar et al. (1993)(41)India Area in Madras ( n = 43 097) Door-to-door survey and key informants 0.41 (ICD-9)
Wig et al. (1993)(42)India A rural area ( n = 1 036 868) and 
 an urban area ( n = 348 609) in 
 Northern IndiaCase-to-case ﬁ  nding and key informants 0.38 (urban, ICD-9); 0.09 
  (urban, Catego S+); 0.44
(rural, ICD-9); 0.12 
(rural, Catego S+)
Brewin et al. (1997)(43)UK Nottingham Two cohorts of ﬁ  rst contacts (1978–80 
 and 1992–94)0.25→0.29 (All psychoses, ICD-10); 
0.14→0.09 (ICD-10 schizophrenia)
Mahy et al. (1999)(44) Barbados Total population ( n = 262 000) First contacts; PSE interviews; Catego (0.32 ICD-9); (0.28 Catego S+)
Bresnahan et al. (2000)(45) USA (California) Birth cohort ( n = 12 094) Case register study; cumulative risk by 
 age 380.93 (males, DSM-IV) 
0.35 (females, DSM-IV)

545
age group 20 to 24 years; thereafter the rate of inception remains 
more or less constant at a lower level. In women, a less prominent peak in the age group 20 to 24 years is followed by another increase in incidence in age groups older than 35. While the age-speciﬁ  c 
incidence up to the mid-thirties is signiﬁ  cantly higher in men, the 
male-to-female ratio becomes inverted with age, reaching 1:1.9 for onsets after age 40 and 1:4 or even 1:6 for onsets after age 60. There seems to be no real ‘point of rarity’ between the symptomatology of late-onset schizophrenia and schizophrenia of an early onset.
The sex differences in mean age at onset are unlikely to be an 
invariant biological characteristic of schizophrenia. For example, within families carrying high-genetic risk (two or more affected members), no signiﬁ  cant differences in age at onset have been 
found between male and female siblings with schizophrenia. 
In some populations (e.g. India and China) the male predominance

In some populations (e.g. India and China) the male predominance 
in the frequency of onsets in the younger age groups is attenuated or even inverted.
(46,47)
The question of whether the total lifetime risks for men and 
women are about the same, or different, has not been answered deﬁ nitively. In the WHO 10-country study, the cumulated risks 
for males and females up to the of age 54 were found to be approx-imately equal. Scandinavian studies which followed up population cohorts into very old age (over 80) reported a higher cumulated lifetime risk in women than in men.
(48)
Male–female differences  have been described in relation to the

(48)
Male–female differences  have been described in relation to the 
premorbid history (better premorbid functioning in women), the occurrence of brain abnormalities (more frequent in men), course (a higher percentage of remitting illness episodes and shorter hospital stay in women), and outcome (higher survival rate in the community, less disability in women). However, there is no unequivocal evidence of consistent sex differences in the symptom proﬁ les of schizophrenia, including the frequency of positive and 
negative symptoms. Generally, the sex differences described in schizophrenia are more likely to result from normal sexual dimor-phism in brain development, as well as from gender-related social roles, rather than from sex-speciﬁ  c aetiological factors.
Fertility, mortality, and comorbidity
(a) Fertility
Earlier studies reported low fertility in both men and women diag-

nosed with schizophrenia. The mean number of children fathered by men with schizophrenia in Sweden was 0.9, and the average 
number of live births over the entire reproductive period of women treated for schizophrenia in Norway between 1936 and 1975 was 1.8, compared with 2.2 for the general female population.
(49)
Y et this phenomenon is neither universal nor consistent over time. In the WHO 10-country study,
(9) the fertility of women with

(49)
(9) the fertility of women with 
schizophrenia in India did not differ from that of women in the general population within the same age groups and geographic areas. Although men with schizophrenia continue to be reproduc-tively disadvantaged, the fertility of women with schizophrenia has increased over the last decades and this trend is likely to be sustained as a result of deinstitutionalization and the greater number of people with mental disorders being able to live in the community.
(b) Mortality

Excess mortality associated with schizophrenia has been well docu-mented by epidemiological studies on large cohorts. National case register data for Norway, 1926–1941 and 1950–1974, indicate that, while the total mortality of psychiatric patients was decreasing, the relative mortality of patients with schizophrenia remained unchanged at a level higher than twice that of the general popula-tion.
(6) Similar ﬁ  ndings have been reported from other European 
countries and North America, with standardized mortality ratios of 2:6 or higher for patients with schizophrenia, which corresponds to about 20 per cent reduction in life expectancy. A meta-analysis  of 
18 studies
(50) estimated a crude mortality rate of 189 deaths 
per 10 000 population per year and a 10-year survival rate of 81 per cent. Mortality among males was signiﬁ  cantly higher than

18 studies
per 10 000 population per year and a 10-year survival rate of 81 per cent. Mortality among males was signiﬁ  cantly higher than 
among females, and the difference was primarily due to an excess in suicides and accidents. Unnatural causes apart, the leading causes of death among schizophrenia patients are similar to those in the general population, with the exception of a signiﬁ  cantly lower than 
expected cancer morbidity and mortality, especially for tobacco-related malignancies in males with schizophrenia.
(51) This puzzling 
phenomenon has been replicated by several case register and record linkage studies
(52,53)  and does not appear to be an artifact. Its causes 
remain unknown, though protective effects of both genes and anti-psychotic pharmacological agents have been proposed.
The single most common cause of death among schizophrenia 
patients at present is suicide  (aggregated standardized mortality

patients at present is suicide  (aggregated standardized mortality 
ratios 9.6 for males and 6.8 for females) which accounts for 28 per cent Table 4.3.5.4  Incidence rates per 1000 population, age 15–54, for a ‘broad’ and a ‘narrow’ case deﬁ  nition of schizophrenia 
(WHO 10-country study)
Country Area ‘Broad’ deﬁ  nition (ICD-9) ‘Narrow’ deﬁ  nition (CATEGO S+)
Male Female All Male Female All
Denmark Aarhus 0.18 0.13 0.16 0.09 0.05 0.07
India Chandigarh (rural area) 0.37 0.48 0.42 0.13 0.09 0.11
Chandigarh (urban area) 0.34 0.35 0.35 0.08 0.11 0.09
Ireland Dublin 0.23 0.21 0.22 0.10 0.08 0.09Japan Nagasaki 0.23 0.18 0.20 0.11 0.09 0.10Russia Moscow 0.25 0.31 0.28 0.03 0.03 0.02United Kingdom Nottingham 0.28 0.15 0.22 0.17 0.12 0.14United States of America Honolulu 0.18 0.14 0.16 0.10 0.08 0.09

(Taken from Report of the international pilot study of schizophrenia, WHO 10-country study, © World Health Organization, www.wh o.int)4.3.5 epidemiology of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 546
of the excess mortality in schizophrenia.(54) The suicide rate in 
schizophrenia patients is at least equal to, or may indeed be higher, than the suicide rate in major depression. In China, the relative risk of suicide in individuals with schizophrenia compared to those without has been estimated at 23.8.
(47) Several risk factors, relatively 
speciﬁ  c to schizophrenia, have been suggested: being young and 
male, experiencing multiple relapses and remissions, comorbid substance use, awareness of the deteriorating course of the condi-tion, and loss of faith in treatment. Data from successive patient cohorts in Denmark,
(55) United Kingdom,(56) and Australia(57)
suggest an alarming trend of increasing mortality in first-admission patients with schizophrenia. In the Danish study,
(55) the

(55) the 
5-year cumulated standardized mortality ratios increased from 5.30 (males) and 2.27 (females) between 1971 and 1973 to 7.79 (males) and 4.52 (females) between 1980 and 1982. Particularly striking was the standardized mortality ratio of 16.4 for males with schizophrenia in the ﬁ  rst year after diagnosis. In the Australian 
study,
(57) suicide risk was highest in the ﬁ  rst 7 days after discharge 
from inpatient care. These trends seem to parallel the signiﬁ  cant 
reductions in the number of psychiatric beds. Whether the increases in suicide mortality are associated with the shift in the manage-ment of schizophrenia from hospital to community care remains to be established.
(c) Comorbidity: physical disease
There is signiﬁ  cant comorbidity in schizophrenia, comprising:

There is signiﬁ  cant comorbidity in schizophrenia, comprising: 
(i) common medical problems and diseases that affect schizophre-nia patients more frequently than attributable to chance; and (ii) certain rare conditions or abnormalities which tend to co-occur with the disorder.
Physical disease is common but tends to be seriously undetected 
and underdiagnosed. Between 46 per cent and 80 per cent of inpatients with schizophrenia, and between 20 per cent and 43 per cent of outpatients, have been found in different surveys to have concurrent medical illnesses.
(58) Persons with schizophrenia, and 
especially those who are homeless or injection drug users, are at increased risk for potentially life-threatening communicable dis-
eases , such as HIV/AIDS, hepatitis C, and tuberculosis.
(59, 60) Among 
the chronic non-communicable diseases, patients with schizophre-nia have signiﬁ  cantly higher than expected rates of epilepsy, diabe-

tes, arteriosclerosis, and ischaemic heart disease.
(61–63) Obesity and 
the concomitant metabolic syndrome  involving insulin resistance 
are becoming increasingly common problems in schizophrenia patients.
(64) Although a high incidence of diabetes  in schizophrenia 
patients had been described long before the introduction ofneuroleptic treatment, a contributing role for some of the second-generation antipsychotic agents has not been ruled out.
Some rare genetic or idiopathic disorders, such as metachromatic 
leucodystrophy, acute intermittent porphyria, and coeliac disease, as well as dysmorphic features such as high-steepled palate, malformed ears and other minor physical anomalies have also been reported to co-occur with schizophrenia.
(65,66)  On the other hand,

(65,66)  On the other hand, 
several studies have found a lower than expected rate of rheuma-toid arthritis in schizophrenia patients.
(67)
(d) Comorbidity: substance abuse
Substance abuse is at present by far the most common associated health problem among patients with schizophrenia
(68) and may 
involve any drug of abuse or a polydrug combination. It seems, however, that the addictive use of cannabis, stimulants, and nicotine 
is disproportionately high among schizophrenia patients and may be linked to the underlying neurobiology of the disorder.
(69,70) In a 
nationwide sample of patients with psychotic disorders in 
Australia,(28) a lifetime diagnosis of comorbid drug abuse, or depen-
dence was made in 36.3 per cent of males and 15.7 per cent of females with schizophrenia (compared to 3.1 per cent and 1.3 per cent respectively in the general population). In addition to poor prognosis of schizophrenia in patients with heavy cannabis use,
(71) a

(71) a 
systematic review  of published data on cannabis  exposure and the 
onset of schizophrenia(72) concluded that early use increased the 
risk of psychosis in a dose-related manner, especially in persons at high genetic risk of schizophrenia. Similarly, stimulants  tend to 
exacerbate acute psychotic symptoms in over 50 per cent of schizo-phrenia patients.
(73) The prevalence of cigarette smoking  among 
schizophrenia patients is, on the average, two to three times higher than in the general population,
(74) but the evidence regarding any 
adverse effects of nicotine use on the onset and course of schizo-phrenia is equivocal. A population cohort study
(75) found that 
smoking at ages 18–20 was associated with a lower risk of schizo-phrenia in later life and could have a speciﬁ  c neuroprotective effect 
independent of its overall harmful impact on health.
Geographical and cultural variation
T o date, no population or culture has been identiﬁ  ed in which

T o date, no population or culture has been identiﬁ  ed in which 
schizophrenic illnesses do not occur. Also, there is no strong evidence that the incidence of schizophrenia is either uniform, or varies widely across populations, provided that the populations being compared are large enough to minimize the effects of small-area variation. The evidence that speciﬁ  c psychosocial  or cultural 
factors play an aetiological role in schizophrenia is also inconsis-tent.
(76) However, there are well-replicated ﬁ  ndings of variations in 
the course and outcome of schizophrenia across populations and cultures that involve, above all, a higher rate of symptomatic recovery and a lower rate of social deterioration in traditional rural communities. Data supporting this conclusion were provided by the WHO studies
(9) which found a higher proportion of recovering

(9) which found a higher proportion of recovering 
or improving patients in developing countries such as India and Nigeria than in the developed countries. Sampling bias (e.g. a higher percentage of acute-onset schizophreniform illnesses of good prognosis among Third World patients) was not a likely explana-tion. A better outcome in the developing countries was found in patients with various modes of onset, and the initial symptoms of the disorder did not distinguish good-outcome from poor-outcome cases. What causes such differences in the prognosis of schizophrenia remains largely unknown. The follow-up in the WHO studies demonstrated that the outcome of paranoid psycho-ses and affective disorders was also better in the developing coun-tries. Such a general effect on the outcome of psychiatric disorders may result from psychosocial factors, such as availability of social 
support networks, non-stigmatizing beliefs about mental illness,

support networks, non-stigmatizing beliefs about mental illness, 
and positive expectations during the early stages of psychotic illness, as well as from unknown genetic or ecological (including nutritional) factors inﬂ  uencing brain development.
The disease and disability burden of schizophrenia
According to WHO estimates(77,78) no less than 25 per cent of the 
total ‘burden of disease’ in the established market economies is

547
at present attributable to neuropsychiatric conditions. Measured as 
proportion of the disability-adjusted life-years ( DALYs ) lost, 
schizophrenia, bipolar affective disorder, and major depression together account for 10.8 per cent of the total, i.e. they inﬂ  ict on 
most communities losses that are comparable to those due to cancer (15 per cent) and higher than the losses due to ischaemic heart disease (9 per cent).
An epidemiological perspective on risk 
factors and antecedents
Studies on clinical samples suggest a great variety of putative risk 
factors in schizophrenia. As clinical samples are rarely representa-tive and often vulnerable to bias, epidemiological evidence helps in evaluating the signiﬁ  cance of such conjectures. Genetic and envi-
ronmental risk factors are considered further in Chapter 4.3.6.1.
Genetic risk: necessary and sufﬁ  cient?
Family aggregation of schizophrenia is at present the only epide-

miologically well-established risk factor for the disorder, with a relative risk for ﬁ  rst-degree relatives of persons with schizophrenia 
in the range from 9 to 18. Allowing for diagnostic variation, the risk estimates generated by different studies are similar and suggest 
a general pattern of descending risk as the proportions of shared genes between any two individuals decrease.
(79,80)  Although heri-
tability  (commonly estimated at about 80 per cent) provides the 
basis for the search of speciﬁ  c genes and gene networks involved in 
schizophrenia causation, the extent to which genetic vulnerability alone is necessary and sufﬁ  cient to produce the disorder remains

schizophrenia causation, the extent to which genetic vulnerability alone is necessary and sufﬁ  cient to produce the disorder remains 
unclear. While an environmental contribution to the aetiology of schizophrenia is highly plausible, the evidence in support of it is inferential, typically proceeding from the observation that the con-cordance for schizophrenia in monozygotic twins (sharing 100 per cent of their genes) is only about 50 per cent. The majority of inves-tigators now agree that genes and environments should be studied jointly and three models of conjunction have been proposed
(81):
X The effects of predisposing genes and environmental factors are 
additive and increase the risk of disease in a linear fashion;
X Genes modulate the sensitivity of the brain to environmental 
insults;
X By fostering certain personality traits and associated behaviour, 
genes inﬂ  uence the likelihood of an individual’s exposure to 
stressful environments.

insults;
Epidemiological research into possible environmental contribu-
tions to the causation of schizophrenia focuses on three main areas: pre- and perinatal brain damage, factors affecting neurodevelop-ment from infancy to late adolescence, and factors of the social and urban ecology. (See also Chapter 4.3.6.1)
Factors maintaining the incidence of schizophrenia 
in populations
Since the ﬁ  rst epidemiological study on the reproduction patterns 
of people with psychoses,(82) reduced fertility among individuals 
with schizophrenia has been documented by numerous investiga-tors. Coupled with the evidence that the lifetime risk of the disor-der (about 1 per cent) is similar across populations and remains stable over time, the question about factors that sustain the inci-

dence of schizophrenia despite a reduced reproductive ﬁ  tness .
An early hypothesis was proposed in 1964 by Huxley et al.
(83) who 
argued that the high frequency of schizophrenia was evidence of 
‘genetic morphism’ (a balanced polymorphism) whereby the low fertility of affected individuals could be compensated for by a higher than average fertility of clinically unaffected ‘cryptoschizophrenic carriers’ who possessed some selective advantage, e.g. resistance to shock, autoimmune disease, or infection. However, attempts to demonstrate such advantage in terms of disease resistance, adaptability to extreme environments, or ability and creativity, have been unsuccessful. Importantly, the selective advantage hypothesis assumed that schizophrenia was a single-gene disorder with low penetrance, whereas the majority of investigators today agree that schizophrenia is a complex polygenic disorder  with

incomplete or variable expression of the genotype, and widespread locus and allelic heterogeneity. The polygenic model implies that loss of susceptibility alleles resulting from the lower reproductive ﬁ tness of affected individuals would have a negligible effect on the 
overall gene pool in the population. The more recent hypothesis, that de novo  germ-line mutations inherited from an ageing 
father
(84) may be responsible for a substantial proportion of inci-
dent cases of schizophrenia, is difﬁ  cult to reconcile with current 
knowledge that mutation rates for most human genes are within the range of 10
−6 to 10−5 per generation, i.e. their contribution to 
the maintenance of schizophrenia in the population would be insigniﬁ  cant. Considering that both multiple genes and multiple

the maintenance of schizophrenia in the population would be insigniﬁ  cant. Considering that both multiple genes and multiple 
exogenous factors are likely to be involved in the causation of schizophrenia, neither increased fertility in asymptomatic carriers of the risk genes, nor paternal inheritance of germ-line mutations appear to be necessary or sufﬁ  cient for the persistence of the
disorder.
Environmental insults during early development
(a) Season of birth
A 5 per cent to 8 per cent winter–spring excess of schizophrenic births was ﬁ  rst described in 1929
(85) and since then reported by 
numerous studies, mostly in the northern hemisphere (southern hemisphere data are less consistent). Though some of these studies did not have the sample size or statistical design needed to deﬁ  ni-
tively prove or rule out a seasonal effect, winter–spring births  were 
associated with a mild but signiﬁ  cant increase of the relative risk

associated with a mild but signiﬁ  cant increase of the relative risk 
for schizophrenia (RR = 1.11; CI 1.06–1.18) in a large population cohort from Denmark.
(86) Thus, birth seasonality appears to be a 
robust ﬁ  nding in the epidemiology of schizophrenia,(87) though 
few biologically plausible and testable causal hypotheses have been advanced to explain it. One of them is the seasonally increased risk of intrauterine exposure to viral infection.
(b) Prenatal exposure to infection
In utero  exposure to inﬂ uenza  has been implicated as a risk factor 
since a report that a signiﬁ  cant proportion of adult schizophrenia 
in Helsinki was associated with presumed second-trimester in utero
exposure to the 1957 A2 inﬂ  uenza epidemic.(88) Numerous studies, 
attempting to replicate the link between maternal inﬂ  uenza and 
schizophrenia, have since reached conﬂ  icting results, with negative

schizophrenia, have since reached conﬂ  icting results, with negative 
ﬁ ndings reported from an increasing number of studies based on 
large population samples,(89,90) as well as studies including data on 
schizophrenia risk in the offspring of women with prospectively 4.3.5 epidemiology of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 548
recorded inﬂ  uenza infection during pregnancy.(91) However, posi-
tive association between schizophrenia in the offspring and mater-nal infection during pregnancy has been reported for rubella
(92)
and toxoplasmosis(93) and the issue of prenatal infection contrib-
uting to schizophrenia risk merits further study.
(c) Pregnancy and birth complications
Maternal obstetric complications, ranging from placental 
abnormalities in the ﬁ  rst trimester of pregnancy to diabetes, pre-
eclampsia, perinatal hypoxia, and low birth weight, are widely regarded to be risk factors in schizophrenia. This view is supported by a number of studies of small to moderate size, typically using a case-control design and relying on maternal recall of adverse events during pregnancy.
(94) Population-based studies(95,96) using 
prospectively recorded obstetric data tend to report conﬂ  icting or

prospectively recorded obstetric data tend to report conﬂ  icting or 
inconclusive results, with generally small effect sizes (odds ratio less than two) for any positive ﬁ  ndings.
(97) However, several birth 
cohort studies with long-term follow-up have found signiﬁ  cantly 
increased risk of adult schizophrenia in individuals who had sur-vived severe, mainly hypoxic perinatal brain damage .
(98,99) Birth 
weight (adjusted for gestation) is another factor that may have a complex relationship with schizophrenia risk. A large cohort study in Sweden
(100) found a reverse J-shaped association between birth 
weight  and adult schizophrenia, with signiﬁ  cant hazard ratios of

weight  and adult schizophrenia, with signiﬁ  cant hazard ratios of 
7.03 for males of low birth weight (<2500 g) and 3.37 for those of high birth weight (>4000 g). It remains unclear, however, if severe obstetric complications, such as perinatal hypoxia or low birth weight, are capable of raising substantially the risk of schizophrenia in the adult in the absence of increased genetic risk. Maternal schizophrenia is associated with a higher rate of pregnancy compli-cations, including low birth weight,
(101) but it is not known if the

(101) but it is not known if the 
effects of genetic liability and obstetric complications on schizo-phrenia risk in the offspring are additive or interactive. It is also possible that genetic predisposition sensitizes the developing brain to lesions resulting from randomly occurring less severe obstetric complications. Such gaps in knowledge or inconsistencies among research ﬁ  ndings caution against an unqualiﬁ  ed acceptance of 
obstetric complication as a proven risk factor in schizophrenia. Clarification of their role remains an important priority for epidemiological research.
Further information about studies of obstetric complications 
and hypoxic-ischaemic damage as risk factors for schizophrenia can be found in Chapter 4.3.6.1.
Developmental antecedents of schizophrenia
(a) Brain development and neurobehavioural markers
Children at high genetic risk for schizophrenia (i.e. having parents or other ﬁ  rst-degree relatives with the disorder) tend to show early signs

Children at high genetic risk for schizophrenia (i.e. having parents or other ﬁ  rst-degree relatives with the disorder) tend to show early signs 
of aberrant neurodevelopment, including ventricular enlargement on computerized tomography
(102) and decreased activation in the 
prefrontal and parietal regions of the heteromodal association cortex on functional magnetic resonance imaging.
(103) Such imaging
studies are limited by small sample size and their results may not begeneralizable. However, population-based or cohort studies, such as the National Child Development Study in the United Kingdom have demonstrated a higher incidence of abnormal motor and speech 
development  before 2 years of age, and of soft neurological signs 
(poor motor control, coordination, and balance), non-right handed-ness and speech defects between ages 2–15.
(104)(b) Cognitive and neurophysiological markers

Deficits in verbal memory, sustained attention and executive functions, as well as abnormalities in event-related brain potentials and oculomotor control
(105–107) are common in patients with 
schizophrenia and antedate the onset of clinical symptoms. They also occur in a proportion of their clinically normal biological rela-tives, but are rare in control subjects drawn from the general popu-lation (see Chapter 4.3.3). Their speciﬁ  city to schizophrenia needs 
to be investigated in larger population samples. Should such endo-
phenotypes  be validated as biological markers of schizophrenia by 
epidemiological studies, the power of risk prediction at the level of the individual is likely to increase substantially.
(c) Premorbid intelligence (IQ)
In a cohort study from Sweden,(108) involving a 15-year follow-up

In a cohort study from Sweden,(108) involving a 15-year follow-up 
of 109 643 men conscripted into the army at age 18 to 20, the indi-viduals who subsequently developed schizophrenia were compared with the rest of the cohort on the performance of IQ-related tests and tasks at the time of conscription. Controlling for potential confounders, the risk of schizophrenia was found to increase linearly with the decrement of IQ. The effect was mainly attribut-able to poor performance on verbal tasks and tests of reasoning. Similar results have been reported from a study in Israel linking psychometric assessment data of the army draft board with the national psychiatric case register.
(109)
Premorbid social impairment
Individuals who develop schizophrenia as adults are more likelyto manifest difﬁ  culties in social interaction during childhood

(109)
and adolescence than individuals who do not develop schizophre-nia. Among children at increased genetic risk (having a parentwith schizophrenia), those who develop schizophrenia as adults have been found to show poorer social competence at age 7 to12 and more passivity and social isolation in adolescence, ascompared to those who do not develop the disorder.
(110) The
association between early ‘schizoid’ traits and risk of schizophrenia is not restricted to offsprings of parents with schizophrenia. Population-based evidence of early socialization difficulties
(school problems, social anxiety, and preference for solitary play) in children who develop schizophrenia as adults is provided by the prospective study of a national birth cohort in the United Kingdom.
(104) In the Swedish conscript study,(108) poor social

(104) In the Swedish conscript study,(108) poor social 
adjustment during childhood and adolescence was signiﬁ  cantly 
more common among those who subsequently developed schizo-phrenia than among those who did not. It should be noted, how-ever, that the early behavioural traits that tend to be associated with schizophrenia in adult life have low speciﬁ  city and their predictive 
value is limited.
Further information about studies of premorbid social impair-
ment can be found in Chapter 4.3.6.1.
The social and family environment
(a) Early rearing environment
Support for an effect of the early rearing family environment on the risk of developing schizophrenia is provided by a study of a Finnish sample of adopted children  born to mothers with schizo-
phrenia (a high-risk group) and a control sample of adoptees at no increased genetic risk.
(111) Though the rates of adult psychosis

549
or severe personality disorder were signiﬁ  cantly higher in the high-
risk group compared with the control group, the difference was entirely attributable to a subset of the high-risk children who grew up in dysfunctional or otherwise disturbed adoptive families—a result consistent with a gene-environment model of genetic inﬂ  uence 
on a person’s sensitivity to psychosocial adversity.
(b) The urban environment
Earlier hypotheses that urban environments increase the risk of psychosis, either by contributing to causation (the breeder effect) or by attracting vulnerable individuals (the drift effect), have been revived in the light of recent epidemiological ﬁ  ndings suggesting 
that urban birth is associated with a moderate but statistically signiﬁ  cant increase in the incidence of schizophrenia, affective 
psychoses, and other non-affective psychoses.
(112) It remains

(112) It remains 
unclear whether the effect is linked to a factor operating pre- or perinatally, or a factor inﬂ  uencing postnatal development (see also 
Chapter 4.3.6.1).
(c) Social class
Since the 1930s, numerous studies in North America and Europe have consistently found that the economically disadvantaged social groups contribute disproportionately to the ﬁ  rst-admission rate 
for schizophrenia. Two explanatory hypotheses, of social causation
(‘breeder’) and of social selection  (‘drift’), were originally pro-
posed.
(113) According to the social causation theory, the greater

posed.
(113) According to the social causation theory, the greater 
socio-economic adversity characteristic of lower-class living conditions could precipitate psychosis in genetically vulnerable individuals who have a restricted capacity to cope with complex or stressful situations. In the 1960s, this theory was considered to be refuted by a single study
(114) which found that the social class dis-

tribution of the fathers of schizophrenic patients did not deviate from that of the general population, and that the excess of low socio-economic status among schizophrenic patients was mainly attributable to individuals who had drifted down the occupational and social scale prior to the onset of psychosis. As a result, aetio-logical research in schizophrenia in recent decades has tended to ignore such ‘macrosocial’ variables. However, the possibility remains that social stratification, socio-economic status, and acculturation stress are contributing factors in the causation of schizophrenia.
(d) Migrants and ethnic minorities
An exceptionally high-incidence rate of schizophrenia (about 6.0 per 1000) has been found in the African–Caribbean population in the United Kingdom.
(115,116)  The excess morbidity is not restricted

(115,116)  The excess morbidity is not restricted 
to recent immigrants and is higher in the British-born second gen-eration of migrants. Similar ﬁ  ndings of nearly four-fold excess over 
the general population rate have been reported for the Dutch Antillean and Surinamese immigrants in Holland.
(117)
The causes of the phenomenon remain obscure. Incidence 
studies in the Caribbean do not indicate any excess morbidity in the indigenous populations from which migrants are recruited. Explanations in terms of biological risk factors have found little support.
(118,122) A ﬁ nding in need of replication is the signiﬁ  cant 
increase of schizophrenia among the siblings of second-generation African–Caribbean schizophrenia patients compared with the incidence of schizophrenia in the siblings of white patients.
(119)

(119)
Such ‘horizontal’ increase in the morbid risk suggests that an environmental factor may be modifying the penetrance of the genetic predisposition to schizophrenia carried by a proportion of 
the African–Caribbean population. Psychosocial hypotheses involving acculturation stress, demoralization due to racial discrimination, and blocked opportunities for upward social mobility have been suggested but not yet deﬁ  nitively tested (see 
also Chapter 4.3.6.1).
Epidemiological issues for the next decade

The unprecedented growth of basic knowledge about the brain and the human genome opens up novel perspectives and opportunities in the study of complex disorders such as schizophrenia, which integrate concepts and tools of genetics, neuroscience, and epide-miology. Several issues with wide implications for future research are already emerging.
Is schizophrenia a single disease or a group of 
aetiologically distinct disorders?
Schizophrenia is characterized by extensive phenotypic variability 
and likely genetic heterogeneity. These two factors may be contrib-uting disproportionately to the multitude of research ﬁ  ndings
that are inconsistent or difﬁ  cult to replicate and there is increasing 
concern that the categorical diagnostic concept of schizophrenia may not demarcate a biologically homogeneous entity.
(120) The 
likely existence of different subtypes  of the disorder (Bleuler’s

(120) The 
likely existence of different subtypes  of the disorder (Bleuler’s 
notion of a ‘group of schizophrenias’) is rarely considered ingenetic and other biological research into schizophrenia. Disaggregating a complex phenotype  by identifying intermediate 
(endo-) phenotypes and quantitative traits as covariates has been a successful strategy in the genetic study of disorders such as type I diabetes, asthma, and dementia. While the clinical concept of schizophrenia as a broad syndrome with some internal cohesion and a characteristic course over time is well supported by current epidemiological evidence, its dissection into modular endopheno-types with speciﬁ  c neurocognitive and neurophysiological under-
pinnings is beginning to be perceived as a promising approach in schizophrenia genetics. The study of endophenotypes cutting

pinnings is beginning to be perceived as a promising approach in schizophrenia genetics. The study of endophenotypes cutting 
across the conventional diagnostic boundaries may reveal unex-
pected patterns of associations with symptoms, personality traits or behaviours, as well as genetic polymorphisms, providing epide-miology with rich material for hypothesis testing at population level.
Molecular epidemiology of schizophrenia
Notwithstanding the difﬁ  culties accompanying the genetic dissection 
of complex disorders, novel methods of genetic analysis will 
eventually identify genomic regions, genes, and interacting gene 
networks  underlying the predisposition to schizophrenia. The

networks  underlying the predisposition to schizophrenia. The 
majority of genes involved are believed to be of small effect, although one cannot exclude the possibility that genes of moderate effects may also be found, especially in relation to the neurophysi-ological abnormalities associated with schizophrenia. Clarifying the function of such genes will be a complex task. Part of the solu-tion is likely to be found in the domain of epidemiology, since establishing their population frequency and associations with a variety of phenotypic expressions is a prerequisite for understand-ing their causal role. Thus the molecular epidemiology of schizo-phrenia is likely to be the next major chapter in the search for its causes and cures.4.3.5 epidemiology of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 550
Can schizophrenia be prevented?
The increasing investment in early diagnosis and treatment of ﬁ rst 
episodes  of schizophrenia has raised questions whether people 
likely to develop schizophrenia can be reliably recognized prior to the onset of symptoms, and whether early pharmacological, cognitive, or social intervention can prevent the development of the disorder. While early diagnosis and timely treatment of symp-tomatic cases may improve the short- or medium-term outcome, the detection of people at risk with a view to preventative interven-
tion is problematic. Screening young age groups in the population

tion is problematic. Screening young age groups in the population 
by using predictors such as family history of psychosis, obstetric complications, or abnormal eye tracking is likely to result in mul-tiple false-positive and false-negative results and a generally low positive predictive value. Other candidate risk factors have not been evaluated at all epidemiologically. Problems of reliability ofmeasurement apart, population-based screening will pose huge practical and ethical problems of having to treat a large number of individuals who do not have the disorder and missing many others who eventually will develop the disorder. From an epidemiological point of view, pre-symptomatic detection and preventative intervention in schizophrenia do not appear to be feasible for the time being.
After nearly a century of epidemiological research, essential ques-tions about the nature and causes of schizophrenia still await answers. Two major conclusions stand out.

X The clinical syndrome of schizophrenia is robust and can be 
identiﬁ  ed in diverse populations, regardless of wide-ranging 
demographic, ecological, and cultural differences among them. This suggests that a common pathophysiology is likely to under-lie the characteristic symptoms of schizophrenia. On balance, the evidence suggests that schizophrenia incidence and disease risk show relatively modest variation at the level of large population aggregates. However, the study of ‘atypical’ populations or pockets of very high or very low frequency of schizophrenia, such as in genetic isolates or minority groups, may provide novel clues
to the aetiology and pathogenesis of disorder.
X No single environmental risk factor of major effect on the inci-

dence of schizophrenia has yet been discovered. Further studies using large samples are required to evaluate potential risk factors, antecedents, and predictors for which the present evidence is inconclusive. Assuming that methodological pitfalls will be avoided by risk-factor epidemiology, and that multiple environ-mental risk factors of small to moderate effect will eventually be identiﬁ  ed, the results will complement those of genetic research 
which also implicate multiple genes and networks. All this sug-gests that the key to understanding schizophrenia is likely to be in the unraveling of complex gene-environment interactions .
Susser, E., Schwartz, S., Morabia, A., and Bromet, E. (eds.) (2006). 
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Psychiatry ,171, 145–7.4.3.6 Aetiology
4.3.6.1 Genetic and environmental 
risk factors for schizophrenia

One thing that is certain about the aetiology of schizophrenia is 
that there is no single cause. This might reﬂ  ect the fact that the 
schizophrenia construct itself is heterogeneous, such that speciﬁ  c 
subtypes might in the future be found to have speciﬁ  c causes. But 
it is more useful at this stage of our knowledge to conclude that, like other disorders such as ischaemic heart disease and diabetes mellitus, schizophrenia results from the cumulative effects of a number of risk factors. These may be crudely divided into the familial-genetic and the environmental, though there are clearly interactions between the two.
Familial–genetic risk
The most powerful risk factor for schizophrenia is having a relative afﬂ icted with the disorder. Numerous studies have shown that the 
lifetime risk for broadly deﬁ  ned schizophrenia increases from

lifetime risk for broadly deﬁ  ned schizophrenia increases from 
about one per cent in the general population to about 10 per cent cent in ﬁ  rst-degree relatives of patients with schizophrenia and to 
close to 50 per cent in those with two parents with the disorder.
(1)
However, familial aggregation does not prove that a condition is genetically transmitted; to look at this issue we need to turn to adoptee and twin studies.
Adoptee studies offer the opportunity of separating the effects of familiality from genetics. In the ﬁ  rst such study of schizophrenia, 
Heston and Denney
(2) demonstrated that ﬁ  ve out of 47 children of 
mothers with schizophrenia who were adopted away within a few days of their birth, later developed schizophrenia compared with none out of 50 adoptees with no family history of schizophrenia. Similar ﬁ  ndings were reported from the Danish-American Study 
of Rosenthal et al
(3) who found that a signiﬁ  cantly higher propor-

tion of the adopted-away offspring of parents with schizophrenia were classiﬁ  ed as having schizophrenia or ‘borderline schizophre-
nia’ , than were control adoptees. This study originated the concept of the schizophrenia spectrum disorder, which has come to include not only frank schizophrenia but also schizophreniform disorder, as well as schizotypal and possibly paranoid personality disorder.
In an extension of the Danish-American collaboration, Kety 
et al.
(4) took all adoptees in Denmark who had schizophrenia and 
examined their biological and adoptive relatives; unlike the earlier adoption studies this one also used operational deﬁ  nitions of the Contents
4.3.6.1 Genetic and environmental risk 
Paul J. Harrison4.3.6.1 genetic and environmental risk factors for schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 554
schizophrenia spectrum conditions. Fully 23.5 per cent of the biologi-
cal ﬁ rst-degree relatives received a schizophrenia spectrum diagno-
sis compared with only 4.7 per cent of the biological relatives of normal control adoptees; the adoptive relatives of both groups of adoptees had very low rates of spectrum disorders.
Finally, Wender et al.
(5) studied the grown-up children of normal 
individuals who, by mischance, had been placed with an adoptive parent who later developed schizophrenia, and found that they were at no increased risk of the disorder. Thus, adoption studies consistently indicate that the familial aggregation of schizophrenia is determined by individuals inheriting genes from someone with the disorder (or a related spectrum condition) rather than any effect of the intrafamilial culture (e.g. being brought up by a parent with schizophrenia).

Twin studies have come to the same conclusion. Gottesman,(1) who 
reviewed the literature, calculated the average probandwise con-cordance rate for broadly deﬁ  ned schizophrenia in monozygotic 
twins to be 46 per cent, compared with 14 per cent in dizygotic twins. This difference reﬂ  ects that while monozygotic twins share 
all their genes, dizygotic twins share, on average, only half. Further evidence of the effect of heredity comes from the evidence that the concordance rate in 12 pairs of monozygotic twins who were reared apart was 58 per cent.
(1)
The above twin studies preceded the introduction of operational 
deﬁ nitions of schizophrenia. When studies with such deﬁ  nitions 
were carried out, the rates for both monozygotic and dizygotic twins were both lower, but the disparity between the two remained. Cardno et al.
(6) examined 108 consecutive pairs of twins seen at the

(6) examined 108 consecutive pairs of twins seen at the 
Maudsley Hospital in London, and reported probandwise concor-dance rates for DSM-IIIR schizophrenia of 42.6 per cent in mono-zygotic twins and 0 per cent in dizygotic twins.
What is the range of the clinical phenotype 
transmitted?
The fact that an individual can have the same genes as their co-twin 
with schizophrenia but have a better than evens chance of remain-ing non-psychotic indicates that it is not schizophrenia per se  which 
is inherited but rather a susceptibility to it. Further evidence in support of this comes from a study which showed that the offspring of the identical but well co-twins of individuals with schizophrenia carry a risk of the disorder similar to that of the offspring of the affected twin.
(7) Thus, the predisposition is transmitted without 
being expressed as schizophrenia.
As noted earlier, sometimes the predisposition may be expressed

As noted earlier, sometimes the predisposition may be expressed 
as non-psychotic spectrum disorders. In addition, family studies show that relatives of people with schizophrenia also show an increased risk of other psychotic conditions such as schizoaffective disorder, atypical and schizophreniform psychoses, and affective psychosis with mood-incongruent delusions. Thus, the clinical phenotype transmitted encompasses a range of psychotic condi-tions, as well as schizotypal personality disorder and paranoid personality. Within schizophrenia, researchers have asked whether different subtypes are differentially inherited. The results have in general been negative which is not surprising since clinicians know that an individual patient can appear predominantly hebephrenic on one admission and schizoaffective on another. However, there has been a consensus that paranoid schizophrenia is less familial

than other types and is associated with a lower monozygotic twin concordance. Also, very late onset schizophrenia (late paraphrenia) appears to carry less genetic loading than early-onset types.
It has been repeatedly shown that schizophrenic symptoms can 
be summarized as three main factors: delusions and hallucinations (reality distortion), negative symptoms (psychomotor poverty), and disorganization or positive thought disorder.
(8,9) Is schizotypal 
personality particularly closely related to one of these three core syndromes? Mata et al .
(10) showed that schizotypal personality 
scores in non-psychotic relatives were signiﬁ  cantly correlated with

scores in non-psychotic relatives were signiﬁ  cantly correlated with 
the presence of delusions and hallucinations in the probands; indeed, they were also correlated with premorbid schizoptypal traits in the childhood of the probands. Thus, it seems that certain families transmit schizotypal traits which manifest themselves in childhood; some family members remain schizotypal throughout life but in others this predisposition is compounded by other (genetic or environmental) factors so that the individual passes a threshold for the expression of delusions and hallucinations.
Genetic models

From the data reviewed above, we can conclude that schizophrenia cannot be explained by the inheritance of a single major gene. In any case, such simple Mendelian inheritance would be hard to square with the persistence of schizophrenia in the population. Since people with schizophrenia tend to reproduce less frequently than the rest of the population, one would have expected that a single major gene with such damaging consequences would have been selected out of the gene pool.
The evidence is compatible with oligogenic inheritance (a small 
number of genes involved) but most parsimonious is a polygenic model which postulates that a number of genes of small effect are involved. Support for this model comes from the fact that the risk to an individual increases with the number of affected relatives
(1) and also that the monozygotic concordance rate is 
higher for those twins who had an early rather than late onset of psychosis.
(6)

(6)
Family studies also show that the relatives of probands with an 
early onset have a higher morbid risk of psychosis than the relatives of late-onset patients.
(11) These ﬁ  ndings are compatible with the 
idea that schizophrenia is in part a developmental disorder and that some of the susceptibility genes may be involved in the control of neurodevelopment.
(12)
Molecular genetic studies
Researchers have been using molecular techniques to seek the gene or genes that predispose to schizophrenia. The ﬁ  rst technique to 
be used was that of linkage in which large families with several members affected with schizophrenia are studied to try and ﬁ  nd 
a genetic marker that co-segregates with the disease. Two decades 
of linkage studies suggest that no gene can exist which increases the 
overall risk of schizophrenia by more than a factor of around three,

overall risk of schizophrenia by more than a factor of around three, 
and that, therefore, there are likely to be a number of susceptibility genes of small effect. This is the mode of transmission for other 
chronic disorders such as diabetes and hypertension, and, as with 
these disorders, the genetic basis of schizophrenia is beginning to be unravelled. In the past few years, ﬁ  ndings from linkage studies 
have led on to detailed mapping studies of certain chromosomal

555
regions which have in turn implicated specific genes. Those 
for which there is most evidence currently are neuregulin and dysbindin.
Neuregulin
(13): An association between schizophrenia and 
a multi marker haplotype (a pattern of DNA within a gene) of 
Neuregulin 1 ( NRG1 ) on chromosome 8p21–22 was found in an 
Icelandic sample in 2002 and soon replicated in a Scottish popula-tion. Subsequently, neuregulin has been implicated in other studies although the exact haplotype has varied in the different studies.
Dysbindin:  Also in 2002, Straub et al.
(14) reported, in Irish fami-
lies, association between schizophrenia and several SNPs (single nucleotide polymorphisms) and multimarker haplotypes spanning the gene encoding dystrobrevin-binding protein 1 ( DTNBP1 ), or 
dysbindin, located at chromosome 6p22.3. Some but not all other studies have replicated this association.
Another way of identifying susceptibility genes is through the study

Another way of identifying susceptibility genes is through the study 
of chromosomal rearrangements. Thus, Blackwood, et al.
(15) reported 
that a large Scottish pedigree showed strong evidence for linkage between a balanced chromosomal translocation (1, 11) (q42;q14.3) (two portions of the different chromosomes swapping positions with each other) and a broad phenotype consisting of schizophrenia,bipolar disorder, and recurrent depression. T his translocation caused 
the disruption of a gene, termed disrupted in schizophrenia 1 ( DISC1 ). 
Subsequent studies have examined DISC1 in Finnish and US samples, and have suggested that it may be a susceptibility gene for bothschizophrenia and bipolar disorder.
A third approach, that of association studies, takes a gene that is

A third approach, that of association studies, takes a gene that is 
suspected of involvement in the pathogenesis of the disorder and compares the frequency of its various alleles in a series of individuals with schizophrenia as opposed to a control group without schizo-
phrenia. One such gene is the catecholamine O-methyl transferase 
(COMT ) gene which has been extensively investigated because of its 
role in dopamine metabolism, especially in the prefrontal cortex.
(16, 17)
A mis-sense mutation (incorrect unit in the genetic code) generates a valine to methionine substitution at codon 158 (Val158Met), pro-ducing an unstable enzyme with reduced degradation of dopamine. The evidence that this polymorphism is in itself a susceptibility gene is uncertain but as we shall see later, it may compound other risk factors for schizophrenia.
Neuregulin, dysbindin, and DISC 1 are the most replicated

Neuregulin, dysbindin, and DISC 1 are the most replicated 
putative susceptibility genes for schizophrenia but other plausible candidate genes identiﬁ  ed by linkage and follow-up studies such as 
G72 (D–amino acid oxidase activator, DAOA), have been suggested. 
G72 and several of the other putative risk genes appear to carry not only an increased risk of schizophrenia but also of bipolar disorder, and are thus congruent with the results of a twin study 
which suggested substantial genetic overlap between the two major 
psychoses.
Nevertheless, none of the above genes can yet be said to be 
100 per cent proven as a cause of schizophrenia since there remain inconsistencies between the speciﬁ  c risk alleles and haplotypes

100 per cent proven as a cause of schizophrenia since there remain inconsistencies between the speciﬁ  c risk alleles and haplotypes 
among studies. It is unlikely that there is a simple relationship between carrying one risk allele and developing schizophrenia. Rather, an individual may need to carry a number of risk genes and be exposed to several environmental risk factors. In such a dynamic multifactorial model, several genes of small effect inter-act with each other and with time-speciﬁ  c exposure to environ-
mental risk factors contribute to both the onset and outcome of schizophrenia.Biological abnormalities in the relatives of people 
with schizophrenia
Relatives have been examined for some of the biological abnormal-

ities which are found in their kin with schizophrenia. Thus, in the Maudsley Study of families multiply affected with schizophrenia, both the members with schizophrenia and those unaffected rela-tives who appeared to be transmitting the liability to the disorder (so-called obligate carriers) showed larger lateral ventricles than controls.
(18, 19)  McDonald et al .(20) went on to show that such 
families transmit a grey matter pattern that shows deﬁ  cits in fron-
tal and temporal areas and that the greater the genetic liability, the greater the deﬁ  cit.
In the same Maudsley Family Study, the non-psychotic relatives 
exhibited other neurophysiological abnormalities such as an excess of delayed P300 event-related potentials; their prevalence was not as high as in the patients themselves but higher than in unaffected controls.
(21) Those patients who showed an excess of saccadic dis-

tractability errors tended to have relatives with the same eye-tracking abnormalities.
(22) The patients with schizophrenia and their well 
relatives from these multiply affected families also showed more integrative neurological abnormalities than controls.
(23)
These ﬁ  ndings suggest that what is being transmitted is not genes 
for schizophrenia per se  but rather genes for a variety of character-
istics (e.g. schizotypal personality, enlarged lateral ventricles, grey matter deﬁ  cit, delayed P300, integrative neurological abnor-
malities) which may increase the risk of schizophrenia or at least be markers thereof. Individuals can inherit these characteristics without being psychotic; perhaps schizophrenia only ensues when an individual inherits a number of such endophenotypic abnor-malities and passes a critical threshold of risk.
(24)
Advancing paternal age in non-familial schizophrenia

(24)
An interesting ﬁ  nding ﬁ  rst noted over 30 years ago is that schizo-
phrenia is commoner in those whose fathers were old at the time they were born. One of the largest studies to demonstrate this comes from Sipos et al.
(25) who studied the risk of schizophrenia 
in 7 54 330 people born in Sweden. The overall hazard ratio for developing schizophrenia increased with each 10 year increase in paternal age. This association between paternal age and schizo-phrenia has been repeatedly shown to be present in those with no family history of the disorder, but not in those with a positive family history. This stronger association between paternal age and schizophrenia in people without a family history raises the possi-bility that accumulation of de novo mutations in paternal sperm with ageing contributes to the risk of schizophrenia.
Environmental factors

It is evident from above that genes exert a probabilistic rather than a deterministic effect on the development of schizophrenia; envi-ronmental risk factors appear to be necessary for the disease to become manifest in many, if not all, cases.
(26) But what are these 
environmental risk factors?
Pre- and perinatal complications
More than 20 studies have shown that patients suffering from schizophrenia are more likely to have a history of pre- or perinatal complications (collectively termed obstetric complications) than 4.3.6.1 genetic and environmental risk factors for schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 556
are healthy subjects from the general population, patients with 
other psychiatric disorders, and their own healthy siblings.(27)
Some of the studies which reported these ﬁ  ndings were based upon 
interviews with patients’ mothers asking them to recall their preg-nancies; such interviews are obviously open to distortion by recall bias. However, similar ﬁ  ndings have been reported by studies 
examining data collected in obstetric records at the time of birth of patients and controls.
(28) Indeed a meta-analysis of large epide-
miologically sophisticated studies which used contemporary records conﬁ  rmed that there is modest but consistent effect of 
obstetric complications. 
(29)
Of course, it is possible that the excess obstetric complications

(29)
Of course, it is possible that the excess obstetric complications 
in schizophrenia may be the consequence of some pre-existing abnormality. Since the foetus plays an active role in the normal progress of pregnancy and labour, foetal impairment induced by earlier abnormality may itself result in some perinatal complications. Also, some studies have shown that women with schizophrenia who become pregnant tend to have more obstetric complications, possibly owing to their behaviour during pregnancy, for example smoking and not attending antenatal visits.
The term ‘obstetric complications’ covers a broad range of 
obstetric events. An international study on 700 schizophrenic patients and a similar number of controls found that low birth weight, prematurity, and resuscitation at birth were particularly increased in the schizophrenic patients;
(27) other complications

(27) other complications 
that have been implicated include retarded foetal growth and rhe-sus incompatability. Thus, a common characteristic of most of the obstetric complications implicated is that they increase the risk of hypoxia.
Could hypoxic–ischaemic damage be the mechanism that 
increases the risk of later schizophrenia? Children who were subject to cerebral hypoxia at or before birth show an excess of abnormali-ties on MRI scan, of minor neurological signs, and of cognitive and behavioural problems, characteristics also found in many preschizophrenic children.
(30) As one might predict, studies of 
monozygotic twins discordant for schizophrenia have shown that the affected twins have larger lateral ventricles and smaller hippoc-ampi than their well co-twins;
(31,32) furthermore, those twins who 
have been subjected to the most severe perinatal difﬁ  culties have 
the largest ventricles and smallest hippocampi.(33)

Similarly, Stefanis et al .(34) compared hippocampal volume in 
three groups, viz, schizophrenia patients with affected relatives but with no personal history of obstetric complications; schizophrenia patients with no affected relatives but who had a history of signiﬁ  -
cant obstetric complications; and normal controls. Hippocampal volume was normal in the ﬁ  rst schizophrenia group but reduced in 
the second group, implying that it is hypoxic-ischaemic damage rather than genetic predisposition alone that determines decreased hippocampal volume in schizophrenia.
Season of birth and maternal exposure to infection

Many studies have shown (in the Northern Hemisphere at least) that people born in late winter and spring are slightly more likely than expected to later develop schizophrenia. Since respiratory viral infections such as inﬂ  uenza tend to occur in autumn and winter, 
maternal infection might provide the explanation. A number of epidemiological studies have, therefore, addressed the question of whether maternal exposure to inﬂ  uenza during the second trimes-
ter of pregnancy is a risk factor for schizophrenia; some but not all studies have suggested that it is.
(35) One study(36) reported an asso-
ciation between the presence of antibodies to the inﬂ  uenza virus in 
ﬁ rst trimester blood, but not during the other trimesters. The pos-
sibility that prenatal exposure to rubella may have a similarrisk-increasing effect for schizophrenia has been raised, and a signiﬁ  -

cant association has been reported with serologically-documented rubella exposure in gestation
(37) Some studies have implicated 
other infectious agents such as herpes simplex, cytomegalovirus and toxoplasmosis, but there is as yet no consensus as to whether these ﬁ  ndings are replicable or not.
Severe prenatal malnutrion appears to have an effect. Thus, 
children born following the Dutch Hunger Winter when the Nazi occupiers systematically starved the population were shown to have a higher risk of schizophrenia and this ﬁ  nding has recently 
been replicated in a Chinese population.
(38,39)
Childhood risk factors

(38,39)
There is now a wealth of evidence attesting to the fact that a pro-portion of individuals who later manifest schizophrenia show abnormalities in their early development. The evidence for early developmental abnormalities in schizophrenia come from three main sorts of study:
X high-risk studies in which the offspring of parent(s) with schizo-
phrenia are examined;
X follow-back studies where cases of schizophrenia are ascertained, 
and their early developmental trajectory plotted with the help of history from the individual and family, sometimes also including such evidence as school reports; and
X cohort studies, where birth cohorts are followed up prospec-
tively, and individuals who later manifest schizophrenia are compared with the rest of the cohort in terms of their early development.
(a) High-risk studies

Studies of the offspring of mothers with schizophrenia, the so-called ‘high-risk studies’ , show that between a quarter to a half show some deviation from normal in terms of their early develop-ment (reviewed by Davies et al.
(40)) In the neonatal period, there is 
a tendency to hypotonia and decreased cuddliness; in infancy, milestones are delayed; in early childhood, there is poor motor co-ordination; and in later childhood, there are deﬁ  cits in attention 
and information processing. Fish et al.
(41) followed their cohort of 
12 high-risk infants into adulthood. One developed schizophrenia and six showed schizotypal or paranoid personality traits; these authors coined the term ‘pandysmaturation’ to describe the abnor-malities which included delayed motor milestones in the ﬁ  rst two 
years of life.
(b) Follow-back studies

High-risk studies have been criticized on the basis that they are unrepresentative because only a minority of people who develop schizophrenia have a mother with the same illness. Therefore, a separate set of studies of representative groups of patients with schizophrenia have used maternal recall to document the early development of adults with schizophrenia. These have shown impairment of cognitive and neuromotor development and inter-personal problems. These ﬁ  ndings are more commonly reported 
in males than females, and tend to be associated with an early onset of illness.
(42) The ﬁ  ndings are not speciﬁ  c to schizophrenia, being

557
reported also in the early development of some children who later 
manifest an affective psychosis.(43)
Of course, one of the major criticisms of follow-back studies is 
the likelihood of recall bias. Studies that have avoided this problem 
include those which have accessed IQ scores assessed prior to illness onset; these have shown that premorbid IQ is, on average, lower in those, particularly males, who later manifest schizophrenia.
(44, 45)
Another source of material mapping early development has been 
childhood home videos, which have been reviewed by researchers ‘blind’ to whether the individual later manifested schizophrenia.
(46)
In comparison with their healthy siblings, the preschizophrenic children showed higher rates of neuromotor abnormalities (pre-dominantly left-sided) and overall poorer motor skills; the group differences were signiﬁ  cant only at two years of age.
(c) Cohort studies
Cohort studies have overcome many of the criticisms of follow-

back studies. In an investigation of the 1958 British Perinatal Mortality cohort, comprising 98 per cent of all children ( n= 15 398) 
born in the United Kingdom in a certain week in March 1958, Done et al.
(47) compared those who later manifested schizophrenia 
(n= 40), affective psychosis ( n= 35), and neurotic illness ( n= 79) 
with each other as well as with 1 914 randomly selected individuals with no history of mental illness. At age seven years, teacher ratings showed the preschizophrenic children to have exhibited more social maladjustment than controls; the effect was most marked in boys. The preaffective children differed little from normal controls, whilst the preneurotic children (expressly girls) showed some mal-adjustment (over- and under-reaction) at age 11 years.
In a similar study of the 1946 British Birth Cohort, Jones et al.
(48)

(48)
determined that 30 out of 4 746 individuals had, in adulthood, devel-
oped schizophrenia. This group was more likely than the rest of the cohort to show delayed milestones and speech problems, to have a lower premorbid IQ and lower education test scores at ages 8, 11, and 15 years, and to prefer solitary play at ages 4 and 6 years. Perhaps the most inﬂ  uential of all the cohort studies has been the Dunedin Birth 
Cohort Study, which followed the development of 1 037 children through the ages of 3 to 15 years, and assessed them again at the ages of 18, 21, and 26 years.
(49) This study found that poorer motor

development, poorer receptive language, and a lower IQ all increased the risk of subsequently developing schizophreniform disorder by age 26 years. The Dunedin cohort additionally provided evidence that a proportion of children who develop schizophrenia are alreadyexperiencing ‘quasi-psychotic’ phenomena by age 11 years.
(50) These 
phenomena include beliefs that people are reading their minds orfollowing or spying on them, or they are already hearing voices. Children with strong evidence of quasi-psychotic symptomatology were up to 16-times more likely to develop schizophreniformdisorders by the age of 26 years; making these phenomena some of the most powerful early predictors of later psychosis.
T ogether, such studies provide compelling evidence for a

T ogether, such studies provide compelling evidence for a 
tendency of individuals with schizophrenia to show abnormalities in development which antedate the onset of illness. The ﬁ  ndings 
are compatible with the notion that subtle brain abnormalities (which may be genetically or environmentally mediated, or both) underpin schizophrenia. However, it is also possible that some of the childhood risk factors are independent and act in an additive manner to set individuals on an increasingly deviant trajectory towards schizophrenia.Social and geographic risk factors
Recent dogma about schizophrenia has held that the incidence does not vary by time or place, even though such an occurrence would have made schizophrenia unique among diseases! Now this curious belief has been disproved by a raft of studies. In particular, a systematic review by McGrath et al.
(50) concluded that the inci-

dence of schizophrenia shows prominent worldwide variation (up to ﬁ ve-fold), and that it is about 40 per cent greater in men than 
women.
In 1939, Faris and Dunham
(52) reported that an excess of indi-
viduals with schizophrenia was found in certain deprived inner-city areas. These authors suggested that social isolation in poor deprived parts of the city could precipitate schizophrenia. However, subse-quently, their results were interpreted as a consequence of social drift, i.e. the idea that individuals with this illness ‘drift’ down the social scale.
(53) This effect was postulated to result from not only 
the illness itself but also its prodroma and consequences such as loss of employment and estrangement from family. A related ﬁ  nd-
ing is that of lack of upward social mobility in individuals with schizophrenia. For example, Hollingshead and Redlich
(54) reported

(54) reported 
that individuals with schizophrenia to be less likely than expected to attain the socio-economic status of their fathers.
More recently, research has focused on the apparent excess of 
individuals who later manifest schizophrenia, who actually start life in a setting which appears to increase the subsequent risk of schizophrenia. Kohn
(55) stated that ‘... in all probability, lower class 
families produce a disproportionate number of schizophrenics’ but the evidence concerning such ‘social causation’ is contradictory. Thus, Turner and Wagenfeld
(56) reported fathers of schizophrenia 
patients to be themselves over-represented in lower socio-economic groups. However, Jones et al.
(48) did not ﬁ  nd this.
It may be that it is not so much poverty as being born or brought 
up in a city which increases the risk of the disorder. For example, Lewis et al.

(57) found that Swedish conscripts who later manifested 
schizophrenia were 1.65 times more likely to have been born in urban than rural areas. Similarly, Marcelis et al .
(58) reported that 
birth in an urban area of Holland carried twice the risk of later schizophrenia of birth in a rural area. Similar ﬁ  ndings have come 
from Denmark where those individuals born in Copenhagen appear to have twice the risk of schizophrenia of those born in rural areas.
(59) It is now generally accepted that the incidence is 
higher amongst those brought up in urban areas, and that the larger the town, and the longer the individual has lived in the city, the greater the risk. The exact mechanisms underlying this effect remain unclear.
Immigration
Since the classic study of Odegaard in 1932,(60) many studies have

Since the classic study of Odegaard in 1932,(60) many studies have 
reported that migrants are at increased risk of schizophrenia. A recent meta-analysis of 18 studies of migrants from different backgrounds conﬁ  rmed a weighted mean relative risk for ﬁ  rst-
generation migrants of 2.7 (95 per cent CI 2.3–3.2) and for second generation migrants, 4.5 (95 per cent CI 1.5–13.1). Risk was higher for migrants from lower socio-economic countries, and for black 
people moving into predominantly white societies.
(61)
A notable example has come from a series of studies of African-
Caribbeans resident in the United Kingdom, who show amarkedly higher rate of schizophrenia than do their white4.3.6.1 genetic and environmental risk factors for schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 558
British-born counterparts.(62)This is in the absence of any increased 
risk to Caribbeans who remain in the West Indies.(63) The increase 
is striking. The large and sophisticated AESOP study of three English cities demonstrated a ninefold increase in the incidence of schizophrenia among African Caribbeans, and a six-fold increase among those of African origin.
(64) Boydell et al.(65) further demon-
strated that migrants were especially vulnerable if relatively isolated in localities where their own ethnic group were in a small minority. Of particular interest is that this increased risk also pertains to British-born offspring of Caribbean migrants, discounting an explanation in terms of migration stress alone. Furthermore, there is a marked increased risk in the siblings but not the parents of this second generation;
(63) this suggests an environmental effect 
operating particularly upon this second generation.

Initial studies sought to ascertain any evidence of developmental 
disadvantage such as poor maternal nutrition, poor obstetric care, and possible maternal susceptibility to novel viruses. However, these studies have shown that, if anything, African-Caribbean schizophrenic patients in England show less evidence of neurode-velopmental insult than their white counterpart patients. Other research focuses on the possibility that a paranoid reaction to social disadvantage and discrimination may be one factor. The ﬁ  ndings 
relating to skin colour potentially support the notion of perceived or real discrimination being an important variable. Other work suggests that people in certain migrant communities are particu-larly likely to be exposed to risk-increasing factors such as child-hood adversity (e.g. parental separation) and adult social exclusion.
Life events

Brown and Birley(66) reported an excess of life events in the 
3 weeks preceding schizophrenic relapse. Further studies were conflicting in their findings, possibly due to methodological problems. The study of Bebbington et al .
(67) avoided many of 
the methodological pitfalls, assessing life events in 97 psychotic patients (52 with schizophrenia) and general population controls. There was a signiﬁ  cant relationship between life events and onset 
or relapse of schizophrenia, although it was not as strong as for depressive psychosis. One possibility is that certain types of schizo-phrenic patients are particularly vulnerable to relapse following adverse life events. For example, Bebbington et al.
(67) found females 
to be particularly prone, whilst van Os et al.(9) found life events to 
be associated with a less severe good-outcome illness.
There is also evidence that families who exhibit high ‘expressed

There is also evidence that families who exhibit high ‘expressed 
emotion’ (comprising critical comments, hostility, and/or over-involvement) can provide an environment which enhances the risk of relapse in a family member with schizophrenia. Again, cause and effect are difﬁ  cult to tease apart. Thus, it is possible that patients 
with more severe and intractable illnesses may induce more expressed emotion in their relatives. It is clear, though, that family interventions aimed at reducing levels of expressed emotion can be effective in reducing relapse rates in the individual.
Drug abuse

Drug abuse
Numerous studies attest to the fact that illicit substance use is more prevalent in patients with schizophrenia than in the general population; estimates of the prevalence of such comorbidity in individuals with schizophrenia range from 20 to 60 per cent, and are consistently higher than in well controls.
(68)Whether illicit substances actually cause schizophrenia has been 
very contentious. The most robust methodology to consider this issue is a cohort design, and a number of such studies have now investigated whether premorbid exposure to cannabis is associated with an increased later risk of schizophrenia. Arseneault et al .
(69)
reviewed these studies and concluded that cannabis could be con-

(69)
sidered a cumulative casual factor in some cases of schizophrenia, operating in consort with other predisposing factors to ‘tip the scales’ in some individuals who might not otherwise have mani-fested the disorder. This literature needs to be seen in the light of the fact that the vast majority of people who use cannabis do not develop schizophrenia, and the majority of cases of schizophrenia are not caused by cannabis; it has been estimated that the popula-tion attributable fraction for cannabis and schizophrenia is of the order of 5 per cent to 8 per cent.
Similarly, although clinical wisdom suggests that illicit substance 
use has a negative impact on the longitudinal course of schizophre-nia, there are few methodologically sound studies in this area.
(70, 71)
Indeed, even the ﬁ  nding of an excess of use, and the association of

(70, 71)
Indeed, even the ﬁ  nding of an excess of use, and the association of 
such use with a poor longitudinal course, is potentially explicable by confounding factors such as substance abuse by the patients who are more ill. On balance, though, it seems reasonable to con-clude that illicit substances make the longitudinal course of illness worse, and that patients with schizophrenia should be strongly advised to seek help to cease such behaviours.
Risk factors, age of onset, and outcome
Individuals who have been exposed to certain risk factors for schizophrenia tend have an earlier onset of psychosis than those who have not. Thus, age of onset is earlier in those whose relatives show a high morbid risk of schizophrenia;
(11) similarly, those 
twin pairs in which the schizophrenia has an early onset show the highest monozygotic concordance.
(6)
Schizophrenia patients with an early age at onset of psychosis

(6)
Schizophrenia patients with an early age at onset of psychosis 
are also more likely than those with later onset to have had a history of exposure to obstetric complications,
(72) while those who showed 
childhood deﬁ  cits such as low IQ also tend to have an early onset.(45)
Schizophrenia patients who abuse cannabis have also recently been 
shown to have an earlier onset than those who do not.
If a factor operates to increase the risk of schizophrenia and to

If a factor operates to increase the risk of schizophrenia and to 
bring on its onset, then it is logical to think that if it is still present then it will be associated with a poor outcome. Thus, a family his-tory of schizophrenia, a history of obstetric complication, child-hood low IQ, and continued drug abuse are all associated with a poor outcome. On the other hand, those patients who develop psychosis following stressful life-events tend to have a better out-come than those with no such precipitant.
(9)
The risk factor model: Gene–environment 
interaction
Thus, one way of construing the aetiology of schizophrenia is to see

(9)
Thus, one way of construing the aetiology of schizophrenia is to see 
individuals on a stress-vulnerability continuum in which genetic and environmental factors act in an additive manner until a thresh-old of liability for expression of psychosis is passed. An individual might, for instance, inherit a schizotypal personality but not develop frank psychosis unless exposed to some cerebral insult which

559
causes cognitive impairment; the sum of the two factors could 
produce the psychotic illness.
Assuming such a model in which a number of genes and envi-
ronmental factors of small effect act additively, then the heritability of schizophrenia can be calculated to be between 66 and 85 per cent (i.e. a high proportion of liability to the disorder is under genetic inﬂ uence). However, this assumes that the various factors operate 
additively, and much evidence is against this assumption. Rather, it seems that there is often an interaction between genetic suscepti-bility and environmental effects. As van Os and Marcelis
(26) point 
out, it seems that certain individuals exposed to an environmental risk factor have a high risk of developing schizophrenia while others with a different genotype are at low risk.
Thus, the quality of upbringing can interact with genetic predis-

position. For example, the Finnish Adoption Study has shown that when the offspring of women with schizophrenia are placed in a well-adjusted family, they have a lower risk of developing a schizo-phrenia spectrum disorder than if they are placed in a dysfunctional family, i.e the genotype renders the individual susceptible to the adverse effect of an adverse family environment.
(73) Obstetric com-
plications also appear to interact with, and compound, a genetic lia-bility; the offspring of parents with schizophrenia are more likely to develop increased ventricular size following obstetric complications.
Similarly, there is evidence that individuals with a family loading 
for schizophrenia may be more susceptible to psychosis following abuse of cannabis.
(74) The latter situation may be complicated by

(74) The latter situation may be complicated by 
the possibility that individuals who inherit certain personality characteristics may be more likely to take drugs such as cannabis, i.e. their genotype renders them more liable to expose themselves to a factor to which they are genetically susceptible. Caspi et al.
(75)
investigating the Dunedin birth cohort study, presented evidence 
of a gene by environment (G x E) interaction between a functional polymorphism in the catechol-O-methyltransferase gene (COMT) and exposure to cannabis. The enzyme COMT has an essential role in the breakdown of dopamine in the prefrontal cortex. Caspi and colleagues showed that COMT moderates the inﬂ  uence 
of adolescent cannabis use, with at least a ﬁ  ve-fold increased risk of

of adolescent cannabis use, with at least a ﬁ  ve-fold increased risk of 
developing schizophreniform disorder in cannabis users homozy-gous for the high activity Val allele (COMT); the Met/Met status offered relative protection (OR =1.1) while risk for heterozygotes 
was intermediate (OR =2.5). Furthermore, there was no correlation 
between the COMT genotype and cannabis use, indicating that COMT genotype does not inﬂ  uence cannabis consumption. This 
appears to be a the ﬁ  rst clear example of a speciﬁ  c gene x environ-
mental interaction predisposing for schizophrenia, but it remains 
to be replicated.
The implications
Having identiﬁ  ed various risk factors for schizophrenia, we can

Having identiﬁ  ed various risk factors for schizophrenia, we can 
proceed to consider the theoretical possibility of reducing the prevalence of certain risk factors and thus reducing the incidence of the disorder. From the point of view of public health, rare risk factors which have a big effect are much less important than common risk factors of even small effect. Thus, although familial risk has by far the biggest effect, it makes a smaller contribution to the total incidence of the disorder than environmental effects. Therefore, if all cases with an affected ﬁ  rst-degree relative could be 
prevented, we would eliminate only about 10 per cent of the total cases. However, because being born in an urban area is so common,

prevented, we would eliminate only about 10 per cent of the total cases. However, because being born in an urban area is so common, 
this small effect accounts for a much greater proportion of the population attributable fraction (33 per cent), i.e. if we could bring down the incidence of schizophrenia in cities to that in the coun-tryside, we could theoretically eliminate one-third of all cases of the disorder. Of course, we could only do this if we knew what the critical urban factors were!
The importance of the evidence that early developmental factors

The importance of the evidence that early developmental factors 
are involved in the aetiology of schizophrenia lies in the fact that at least some of these are preventable. For example, advances in ante-natal and perinatal care have reduced the frequency, and toxicity, of some obstetric complications. Similarly, vaccination programmes have reduced exposure to some viral infections in pregnancy and childhood. There could be a link between these developments and the decreased incidence of schizophrenia which has been observed in some western countries over recent decades.
(76)
Nevertheless, most babies who are exposed to even severe obstetric

(76)
Nevertheless, most babies who are exposed to even severe obstetric 
complications will not later suffer from schizophrenia. Thus, there is at present no sense in attempting to improve antenatal care with the aim of reducing the occurrence of schizophrenia. There is one important exception. It is indisputable that the children of schizo-phrenic mothers have a higher risk of the disease if they are also exposed to obstetric complications. Therefore those women with schizophrenia who conceive must have the best possible antenatal care during their pregnancy, and steps should be taken to avoid any event (e.g. prolonged labour) which might lead to hypoxic damage to 
the baby.
The fact that preschizophrenic children show a number of 
impairments raises the possibility that predisposed individuals could be identiﬁ  ed and ‘rescued’ by some intervention. Unfortunately, 
the childhood characteristics of such children are non-speciﬁ  c, and

the childhood characteristics of such children are non-speciﬁ  c, and 
their predictive value for the later manifestation of the illness is too low to be of value for any preventative intervention, i.e. many children who show such deviation from normal in terms of early development do not later manifest schizophrenia, whilst other children who later develop schizophrenia have perfectly ‘normal’ early development. Furthermore, any such abnormalities must be seen in the total context of development, and it should be remem-bered that many such abnormalities are not static, but may be evi-dent at some stages of development and not at others.
One might think that there is as yet little that can be done

One might think that there is as yet little that can be done 
systematically to reduce the incidence of schizophrenia. However, one area where prevention is possible concerns drug abuse. The evidence concerning the abuse of cannabis is clear. If the popula-tion could be persuaded to avoid heavy use of cannabis, particu-larly the more potent varieties, then it is likely that a small but nevertheless signiﬁ  cant proportion of cases of schizophrenia could 
be avoided.
Murray R.M., Jones P .B., Susser E., et al. (eds.) (2003) The Epidemiology 
of Schizophrenia . Cambridge: Cambridge University Press.
Van Os J., Marcelis, M. (1998) The ecogenetics of schizophrenia: a review. 
Schizophrenia Research ,32, 127–35.
Harrison, P .J., Owen, M.J. (2003) Genes for schizophrenia? Recent ﬁ  ndings 
and their pathophysiological implications. Lancet ,361, 417–419.
Jones, P ., Cannon, M. (1998) The new epidemiology of schizophrenia.

Jones, P ., Cannon, M. (1998) The new epidemiology of schizophrenia. 
Psychiatric Clinics of North America ,21, 1–25.4.3.6.1 genetic and environmental risk factors for schizophrenia

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4.3.6.2 The neurobiology 
The neurobiology of schizophrenia remains the subject of intense 
research activity. Here, the key issues and ﬁ  ndings are described, 
divided into functional and structural aspects, and followed by a summary of the major neurobiological theories. Where possible, meta-analyses and systematic reviews are cited in preference to individual studies.

Functional neurobiology of schizophrenia
Dopamine
The dopamine hypothesis of schizophrenia has been neurochemi-cally pre-eminent since the 1960s.
(1) It proposes that the symptoms 
of schizophrenia result from dopaminergic overactivity, whether due to excess dopamine, or to an elevated sensitivity to it, for example because of an increased number of dopamine receptors. The hypothesis originated with two complementary observations: that effective antipsychotics were dopamine (D
2) receptor antago-
nists, and that dopamine-releasing agents such as amphetamine produce a paranoid psychosis.
(2) It received support from various 4.3.6.2 the neurobiology of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 562
ﬁ ndings of increased dopamine content and higher densities of D2
receptors in post-mortem brain studies of schizophrenia, but 
proved difﬁ  cult to reﬁ  ne or refute, for two main reasons. First, 
predictably, antipsychotics have marked effects on the dopamine system, confounding all studies of drug-treated subjects. Second, molecular biology revealed an unexpected complexity and diversity of dopaminergic genes, increasing the number of potential sites of dysfunction and mechanisms by which it might occur. For example, soon after the D
4 subtype of dopamine receptor was cloned, there 
were high proﬁ  le reports that the receptor was up-regulated several-
fold in schizophrenia, and might also be relevant for the actions of clozapine. However, neither suggestion was conﬁ  rmed by further 
studies, and interest in this topic has subsided.
Despite these difﬁ  culties, substantial support for the dopamine

Despite these difﬁ  culties, substantial support for the dopamine 
hypothesis has now emerged, attributable largely to the availability of imaging-based methods to assess the dopamine system in the brain in vivo, free of medication, and post-mortem confounds. Notably, there is now strong evidence for a pre-synaptic dopamine abnormality, with several studies showing elevated dopamine synthesis, release, and higher dopamine receptor occupancy in the striatum.
(3) The findings indicate a dysregulation and hyper-

responsiveness of dopaminergic neurones in schizophrenia, sometimes referred to as ‘hyperdopaminergia’ . These abnormalities are present in patients with acute psychosis but not in patients in remission; recent data suggest that they may also occur in subjects in the prodrome of schizophrenia, and that they are localized to the associative parts of the striatum. It is not known whether the ﬁ ndings are speciﬁ  c to schizophrenia or common to other acute 
psychoses, whether they also affect dopamine pathways in the cerebral cortex, and whether they apply in all subjects with schizo-phrenia.
(4) Neither is the cause of the hyperdopaminergia under-
stood; one hypothesis is that it is downstream of a developmental deﬁ cit in the glutamatergic projections that regulate dopamine 
transmission,
(5) another that it involves an imbalance between 
phasic and tonic modes of dopamine release.(6)

In addition to the excessive dopamine function associated with 
acute psychosis, there is also increasing evidence that deﬁ  ciencies 
in dopamine transmission, especially in the dorsolateral prefrontal cortex, and genetically influenced, may underlie the working memory and allied cognitive deﬁ  cits that occur in the disorder.
(7)
The relationship between these two facets of dopaminergic involve-
ment in schizophrenia is not understood.
Glutamate
Phencyclidine and other non-competitive antagonists of the N-methyl- d-aspartate (NMDA) subtype of glutamate receptor 
produce a psychosis closely resembling schizophrenia.
(8) This has 
driven the hypothesis of glutamatergic dysfunction in the disorder, particularly a disturbance of NMDA receptor-mediated glutamate transmission.
(9) In support, drugs that enhance NMDA receptor

(9) In support, drugs that enhance NMDA receptor 
function (via a variety of indirect mechanisms, since direct ago-nists are toxic) have some beneﬁ  cial effects on positive, negative, 
and cognitive symptoms.
(10) Also, impairment of NMDA receptor 
function in animal models, induced by either genetic or pharmaco-logical manipulation, produces behavioural, structural, and neurochemical findings consistent with a ‘schizophrenia-like phenotype’ .
(11,12) There is also a range of alterations in parameters 
of glutamate transmission in subjects with schizophrenia, including levels of glutamate receptors and of endogenous glutamate recep-
tor modulators such as d-serine.(9,13)  Interest in the glutamate sys-

tem has been heightened with the realization that many of the putative susceptibility genes for schizophrenia have effects on NMDA receptors and their pathways
(14) (see below).
Other neurotransmitters
A 5-hydroxytryptamine (5-HT, serotonin) involvement in schizo-phrenia was suggested because the hallucinogen lysergic acid dieth-ylamide (LSD) is a 5-HT agonist. Recently, interest has focused on the 5-HT
2A receptor, for several reasons.(15) There is lowered 5-HT2A
receptor expression in the frontal cortex in schizophrenia, and a blunted neuroendocrine response to 5-HT
2 agonists; a high afﬁ  nity 
for the receptor may contribute to the proﬁ  le of atypical compared 
to typical antipsychotics, and variants in the gene are weakly asso-ciated with response to clozapine, and perhaps with schizophrenia. Elevated cortical 5-HT
1A receptors are also a replicated ﬁ  nding.

1A receptors are also a replicated ﬁ  nding. 
Explanations for 5-HT involvement in schizophrenia include the trophic role of the 5-HT system in neurodevelopment, interactions between 5-HT and dopaminergic neurones, and impaired 5-HT
2A
receptor-mediated activation of the prefrontal cortex.
GABA, the major inhibitory transmitter in the brain, has been 
implicated in schizophrenia, on the basis of ﬁ  ndings of alterations 
in speciﬁ  c markers of GABAergic neurones and their connections 
as well as changes in GABA receptors.(16,17) The position of these 
alterations in the pathogenesis of schizophrenia is not known, as is also the case for the many other neurochemical differences that have been reported, e.g. in neuropeptides, endocannabinoids, muscarinic receptors, etc.
(18)
Functional neuroimaging and cerebral activity

(18)
Cerebral activity in schizophrenia has been investigated by several methods, initially using positron emission tomography to measure regional cerebral blood ﬂ  ow and glucose utilization, and more 
recently using functional magnetic resonance imaging. The studies have addressed several questions: are there differences between cases and controls at rest, or correlations between patterns of activity and clinically deﬁ  ned groups of subjects, or does brain 
activation during the performance of cognitive tasks differ in those with and without the illness?
Hypofrontality—decreased activity in the frontal lobes—has been 
widely studied in schizophrenia since the ﬁ  rst report in 1974. Results 
have broadly supported the notion, but with several important qualiﬁ  cations. The current view is that, whilst hypofrontality does 
occur in unmedicated subjects,
(19) it is not an invariable ﬁ  nding,

(19) it is not an invariable ﬁ  nding, 
and may be related to clinical state.(20) Similarly, there are few other 
robust baseline differences in cerebral activity or perfusion between cases and controls. Instead, the focus has shifted towards the link between regional patterns of activation with speciﬁ  c symptoms, or 
with performance during cognitive tasks. Among the former cate-gory, a well-known example is that of Liddle et al.
(21) who found 
that each of the three subsyndromes of chronic schizophrenia they had identiﬁ  ed by factor analysis was associated with a different 
regional proﬁ  le of cerebral blood ﬂ  ow. A relationship between supe-
rior temporal gyrus metabolic activity and auditory hallucinations has often been reported, sometimes lateralized to the left hemi-sphere.
(22) Many other correlations between regional patterns of 
(de)activation and individual symptoms have also been reported.

563
A number of studies have investigated regional brain activation 
during the performance of various neuropsychological tests. For example, the hypofrontality of schizophrenia can be seen most clear-ly during working memory tasks, such as the Wisconsin Card Sort T est, which require activation of the frontal lobes, and at which patients are impaired. Conversely, when groups are matched for per-formance, subjects with schizophrenia show increased activation of these areas compared to controls, suggesting that they are less ‘efﬁ  -
cient’ in how the information is processed, and requir greater ‘effort’ to achieve the same result. These issues illustrate that the situation is more complex than simply hypo- (or hyper-) frontality, but rather that there is a dynamic disturbance of frontal cortex function and regulation.
(23) Beyond working memory and hypofrontality, a range 
of other speciﬁ  c correlations of this kind have been reported, but the

of other speciﬁ  c correlations of this kind have been reported, but the 
key conclusion of this research is that cerebral dysfunction in schizo-phrenia is better conceptualized not as reﬂ  ecting a static or single 
focal disorder, but as arising from abnormalities in distributedcircuits linking speciﬁ  c cortical areas and subcortical nuclei. A prom-
inent model is that of Andreasen,
(24) who proposed the concept
of ‘cognitive dysmetria’ , in which deﬁ  cits in activity in a circuit involv-
ing the cerebral cortex, thalamus, and cerebellum are key, and under-lie the memory difﬁ  culties of schizophrenia. The view of the disorder 
as one of disturbed neural connectivity affecting multiple brain regions and their integration is supported by structural imaging and neuropathological data (see below). The model also highlightstwo other recent research themes: ﬁ  rst, that brain areas beyond the

‘traditional’ ones (e.g. prefrontal cortex, hippocampus) and their interconnections are involved in the pathophysiology of the disor-der; the most notable region of this kind is the cerebellum, formerly overlooked because of the erroneous view that it is entirely involved in motor control.
(25) Second, the model places the cognitive deﬁ  cits 
of schizophrenia centre stage in its pathophysiology, a view that was neglected for many years, but has regained prominence and is now widely cepted (Refs
26–28; see Chapter 4.3.3).
Electrophysiology
A number of electrophysiological indices are altered in schizophre-nia, and are relevant to the understanding of its neurobiology.
(29)
First, evoked potentials (electrical activity in the brain measured after a brief sensory stimulus); in particular, the P300 component is reduced and delayed in response to auditory and visual stimuli, indicative of impaired sensory processing.
(30) Second, there is a

(30) Second, there is a 
high rate of eye movement abnormalities in schizophrenia, especially affecting smooth pursuit tracking, suggestive of impair-ment in the neural pathways subserving oculomotor control.
(29)
There are also differences in the cortical signal to noise ratio in the electroencephalogram, suggestive of an impairment of cortical information processing,
(31) and consistent with the hypothesized 
abnormalities in cortical neural circuitry.
Structural neurobiology of schizophrenia

Finding the neuropathology of schizophrenia has been one of the major quests of biological psychiatry for over 100 years. Indeed, Alzheimer wrote a paper on the subject in 1897, 10 years before he described the disease that bears his name. However, whilst funda-mental neuropathological discoveries were made in the dementias, there was no such progress for schizophrenia. In the past 20 years or so, the situation has changed. There is now compelling evidence that there is a neuropathology of schizophrenia, in the sense that

there are statistically robust structural differences in the brains of patients with the disorder compared to normal subjects, both on structural imaging and at post-mortem (Table 4.3.6.2.1). On the other hand, the details and meaning of these changes are still elusive, and they are of limited clinical utility—they are not diag-nostically speciﬁ  c, and they are only demonstrable when groups of 
cases and controls are compared.
Structural neuroimaging and macroscopic ﬁ  ndings
The landmark study of Johnstone and colleagues showed, using 
computerized tomography, enlargement of the lateral ventricles in schizophrenia.
(32) Although similar ﬁ  ndings had been reported by 
pneumoencephalography, it was this paper which stimulated the ﬁ eld. It has been followed by many imaging studies, mostly in the 
last 20 years using magnetic resonance imaging,
(33) and several

(33) and several 
meta-analyses. The latter show clearly that ventricular enlargement (with an average volume increase of ~40 per cent) is a feature of schizophrenia.
(34–36) Accompanying this change there are decreases 
in cortical and whole brain volume of ~3 per cent,(36, 37)  paralleled 
by a similar reduction of brain weight.(38) The regional localization 
of volume deﬁ  cits is less clear, with different studies and meta-
analyses implicating the hippocampus,(39) left superior temporal 
gyrus and medial temporal lobe (including hippocampus),(40)
other regions of cerebral cortex, and thalamus.(41) For a narrative 
review of structural MRI studies, see Shenton et al.(42)
Structural brain changes are present in ﬁ  rst episode patients.(43)
Some differences are also present in subjects before they develop

Some differences are also present in subjects before they develop 
psychosis,(44,45)  as well as in unaffected relatives,(46) indicating that 
part of the structural pathology is related to risk for schizophrenia (whether genetic or otherwise). Equally, other volumetric changes develop in high-risk subjects when they develop psychosis(e.g. hippocampal volume loss), suggesting that these changes are state-related rather than trait-related.
(45, 47)
Two issues regarding structural imaging in schizophrenia remain 
controversial. First, the extent to which changes are progressive Table 4.3.6.2.1  Morphological ﬁ  ndings in schizophrenia
Replicated positive ﬁ  ndings
 Enlarged lateral and third ventricles Decreased brain size and weight
 Decreased cortical volume, especially temporal lobes
 Fewer neurones in pulvinar thalamic nucleus Decreased synaptic markers

Enlarged lateral and third ventricles Decreased brain size and weight
Replicated negative ﬁ  ndings
 No increased incidence of Alzheimer’s disease
 No gliosis
Selected controversial ﬁ  ndings
 Increased density of cortical neurones
 Smaller neurones
 Reduced density of parvalbumin-positive interneurones
 Aberrant distribution of white matter neurones
 Fewer glia (oligodendrocytes) Smaller mediodorsal thalamus with fewer neurones
 Hemispheric asymmetry of pathology
 Decreased dendritic markers Effects of antipsychotic drugs on brain structure4.3.6.2 the neurobiology of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 564
after the onset of established illness.(48) The meta-analyses of the 
cross-sectional studies show no clear evidence of progression (in keeping with the stability of cognitive impairments, and the nature of the neuropathology to be described). On the other hand, several longitudinal studies do report greater shrinkage of various brain regions with time compared to control subjects, leading to patho-physiological theories related to aberrant plasticity and neuro-toxicity.
(49,50) The second controversy, which may be related to the 
ﬁ rst, concerns medication effects. Again, there is little consensus: 
there are positive and negative reports concerning effects of anti-psychotics on whole or regional brain volumes, and some suggest-ing differential effects of typical versus atypical antipsychotics.
(51)
Recent studies are using novel imaging methods to assess the

(51)
Recent studies are using novel imaging methods to assess the 
status of white matter tracts in schizophrenia, to investigate hypo-theses of aberrant anatomical connectivity.
(52) A number of abnor-
malities have been demonstrated, broadly consistent with these notions,
(53) although their interpretation (i.e. what is different 
functionally and/or anatomically) is not wholly clear.
The neuropathology is not degenerative
Despite the continuing uncertainties, the appreciation thatthere are structural brain changes in schizophrenia in terms of magnetic resonance imaging ﬁ  ndings helped stimulate a new
generation of morphometric and molecular post-mortem studies designed to determine the histological and cellular basis of the observations.
The most robust and important histological ﬁ  ndings in schizo-
phrenia are both negative.
(54) Firstly, the neuropathology is not 
degenerative(55–57) : there are no lesions such as neuroﬁ  brillary tan-

gles, amyloid plaques, or Lewy bodies, which would indicate the presence of any known neurodegenerative process.
(56,57)  Importantly, 
this conclusion even applies to the signiﬁ  cant subg roup of elderly 
patients who develop dementia; the neuropathological basis for the dementia of schizophrenia is entirely unexplained.
(56) Secondly, 
there is no excess of gliosis in the brains of patients with schizophre-nia.
(58) Gliosis, the proliferation and hypertrophy of astrocytes, is a 
sign of inﬂ  ammation, injury, or other ongoing pathological pro-

cesses. Hence the lack of gliosis is taken to denote that the disorder is likely to be neurodevelopmental in origin, affecting mechanisms involved in the normal maturation of the brain. Indeed, some recent studies suggest there is actually a decrease in the number or activity of some glial cells, an issue returned to later.
Morphometric and cytoarchitectural changes
Having ruled out these important possibilities, it has been difﬁ  cult 
to pin down just what the histological changes are, and therefore the cellular basis for decreases in regional brain volumes. Nevertheless, the positive ﬁ  ndings can be grouped together and 
viewed as broadly cytoarchitectural in nature—i.e. affecting 
the morphology and spatial organization of neurones and their 
processes (Ref.
(54); Table 4.3.6.2.1).
As a rule, the more dramatic (and well publicized) the initial

As a rule, the more dramatic (and well publicized) the initial 
ﬁ nding, the less robust it has proved to be. For example, dysplasia 
(disorganized, misplaced, and misshapen neurones) in the entorhi-nal cortex was reported in 1986. Such a ﬁ  nding would be strongly 
suggestive of a prenatal developmental anomaly. However, subsequent studies have, at best, only partially replicated this observation. Similarly, a report that pyramidal neurones in the hippocampus are not aligned in their usual regular orientation, also indicative of a developmental disturbance, has not been con-
sistently observed.
A decreased size of neurones, particularly in the hippocampus

A decreased size of neurones, particularly in the hippocampus 
and prefrontal cortex, has been found in several studies. The sizeof a neurone is related to the volume of axon and dendrites,which it has to support, and also to its metabolic activity. Thus,the finding of smaller neurones in schizophrenia suggests theneurones may be receiving and making fewer, abnormal, or less-active connections. Support for this interpretation comes fromstudies of synaptic and dendritic markers, which have been reason-ably consistent in showing decreases in the same brain areas.
(59) It is 
unclear as to which speciﬁ  c populations of neurones and synapses 
are most affected in schizophrenia, and it may vary from one region to another; in both hippocampus and prefrontal cortex, there is evi-dence for involvement of excitatory (glutamatergic) pathways
(60, 61) as 
well subtypes of inhibitory (GABAergic) ones,(16,17) especially the class

(60, 61) as 
well subtypes of inhibitory (GABAergic) ones,(16,17) especially the class 
of parvalbumin-positive interneurones.(17) In addition to the neuro-
nal pathology, several recent studies show reductions in markers of oligodendrocytes and their activity.
(62) This type of glial cell is inti-
mately involved in myelination, and contributes to synaptic homeo-stasis, and therefore their involvement in schizophrenia is in keeping with the occurrence of synaptic as well as white matter pathology.
A further area of interest is the thalamus, speciﬁ  cally the pulvinar 
and mediodorsal nuclei. Both have been found to be smaller and to contain fewer neurones in several studies of schizophrenia; in the case of the pulvinar nucleus, the evidence is amongst the mostcompelling of any brain region, coming from four methodologically rigorous studies (as well as complementary ﬁ  ndings in the imaging 
literature, noted above), and with no corresponding negativestudies.

(63) These thalamic nuclei have extensive reciprocal connec-
tions with the prefrontal and temporal association cortices, andit is assumed that there is some causal link between the changes in each thalamic nucleus and its cortical partner.
Neuropathology and medication effects
Most patients studied neuropathologically were treated in life with antipsychotic drugs, and so the ﬁ  ndings in schizophrenia are open 
to the criticism that they may have been caused by antipsychotic medication.
(64) However, as noted above, many imaging studies 
show that the pathology, at least in terms of the gross alterations summarized in Table 4.3.6.2.1, is present in ﬁ  rst episode and medi-
cation-naïve subjects. Also, in post-mortem studies, the reported neuropathological ﬁ  ndings rarely if ever correlate with the extent of

cation-naïve subjects. Also, in post-mortem studies, the reported neuropathological ﬁ  ndings rarely if ever correlate with the extent of 
antipsychotic exposure. In some instances it may also be that medi-cation ameliorates the disease effects. Nevertheless, the possibility that antipsychotic drugs have neuropathological effects should not be overlooked. Firstly, typical antipsychotics produce enlargement of, and synaptic structural alterations in, the basal ganglia (caudate, putamen, globus pallidus).
(64) Secondly, a recent monkey study 
found that chronic administration of haloperidol or olanzapine at therapeutic levels led to decreased brain volume
(65) along with 
increased neuronal density and decreased glial density,(66) thus 
reproducing several of the changes reported in schizophrenia.
Neurobiological theories of schizophrenia
Schizophrenia as a neurodevelopmental disorder
The neurodevelopmental model of schizophrenia is the prevailing pathogenic hypothesis.

(5,67–69)  Neurobiological data form an

565
important component of the evidence, along with epidemiological 
and other observations (Table 4.3.6.2.2). A speciﬁ  c version of the 
theory is that the pathology of schizophrenia originates in the second trimester in utero . An earlier timing is excluded since overt 
brain abnormalities would be seen if neurogenesis were affected, whilst the lack of gliosis has been taken to mean that the changes must have occurred prior to the third trimester when the gliotic response begins.
(57) Other forms of the neurodevelopmental 
theory advocate abnormalities in processes such as myelination, synaptic pruning, and apoptosis, all of which continue long into post-natal life. Overall, a parsimonious view is that the neuro-pathological data are indicative merely of a basically developmental, as opposed to degenerative, disease process, but do not, in isola-tion, point to a particular mechanism or timing.
Schizophrenia as a disorder of connectivity

The functional imaging and histological data summarized above have together contributed to the emerging consensus that the patho-physiological basis of schizophrenia is one of connectivity.
(24, 54, 70–72)
The nature of the ‘dysconnectivity’ is not a simple lack, or gross mis-routing, of connections, but likely a subtle change in a more ﬁ ne-grained aspect, such as the precise molecular composition, 
location, or activity of subpopulations of synapses.
(71) Both intrin-
sic (local) and extrinsic (long-range) connections may be affected. The extent to which there is a structural basis to the aberrant connectivity remains uncertain,
(73) but in so far as it exists, the

(73) but in so far as it exists, the 
histological basis of the syndrome is a difference in the circuitry, or ‘wiring’ of the brain, manifested by the cytoarchitectural differ-ences in the morphology and organization of neurones and their synapses. If there is indeed a structural basis to the pathophysiolo-gy of the syndrome, it would help explain why many of the cardinal features are trait rather than just state abnormalities, and perhaps why individuals are vulnerable to relapse, in that a ‘miswired’ brain may be less able to respond rapidly, appropriately, or fully to environmental stressors.Cerebral asymmetry and schizophrenia
Many neuropathological, neurochemical, neuropsychological, and electrophysiological studies of schizophrenia report lateralized abnormalities. Although there are also important negative ﬁ  ndings, 
reductions in normal brain asymmetries, and a left hemisphere preference of the pathology, do seem more common than one would expect by chance.

(74,75) Crow’s inﬂ  uential theory sees a 
fundamental connection between schizophrenia, asymmetry, handedness, and language, causally linked to each other and to the same gene.
(76) Alternatively, altered asymmetry in schizophrenia 
is viewed as an epiphenomenon of its developmental origins, a process which interferes with normal brain lateralization.
Susceptibility genes and neurobiology
Given its high heritability,(77) it can be assumed that genes are the 
major inﬂ  uence on the neurobiological features of schizophrenia, 
likely modiﬁ  ed by the various environmental risk factors (see 
Chapter 4.3.6.1). The recent discovery of several probable suscepti-
bility genes(14,78) now allows this question to be addressed more 
speciﬁ  cally, in terms of the normal functions of the genes, and how

speciﬁ  cally, in terms of the normal functions of the genes, and how 
this is altered in those carrying the risk variants of the genes.
Neuregulin 1 (NRG1) is the best established susceptibility 
gene.(79) It encodes a family of proteins that have multiple roles in 
the nervous system, ranging from cell fate determination, to neuro-nal migration, neuronal-glial signalling, and NMDA receptor functioning.
(80) As such, it is a good candidate gene for schizophre-
nia given the existing theories outlined above regarding aberra-tions in neurodevelopment, connectivity, and glutamate synaptic transmission. Equally, at present it is not clear which of these functions is actually affected in schizophrenia or explains the contribution that NRG1 plays in the disease process,
(81) and deter-
mining this will not be simple. Initial data suggest an impairment of NRG1 signalling via its receptors,
(82) and an alteration in the

(82) and an alteration in the 
expression of one speciﬁ  c subtype of NRG1.(83,84)
An interaction with synaptic neurotransmission is also seen for 
most of the other leading susceptibility genes (Table 4.3.6.2.3), leading to the notion that this effect is a point of pathophysiological convergence of the genes.
(14) Such a convergence is an attractive 
concept for several reasons, not least parsimony, but whilst there is some evidence to support it, it remains highly speculative. Indeed, Table 4.3.6.2.2  Evidence adduced for a neurodevelopmental basis 
to schizophrenia
X Usual age of onset in late adolescence and early adulthood
X Most environmental risk factors operate prenatally or in early childhood
X  Neuromotor, intellectual, and behavioural differences in children many years 
prior to onset

X  Structural brain changes and cognitive impairments present at, and prior to, 
onset of illness
X  Nature of the neuropathological ﬁ  ndings—lack of gliosis or 
neurodegeneration, plus cytoarchitectural disturbances
X Changes in expression of neurodevelopmental genes (e.g. reelin)
X  Minor physical anomalies—for example, craniofacial dysmorphology and 
dermatoglyphics. 
X  Animal models—early lesions or pharmacological interventions lead to 
delayed ‘schizophrenia-like’ phenotypes 
(Reprinted from P .J. Harrison, Schizophrenia susceptibility genes and neurodevelopment, 
Biological Psychiatry , 61, 1119–20, copyright 2007, with permission from Elsevier)
For reviews and other references, see text.Table 4.3.6.2.3  Susceptibility genes and their neurobiological 
functions
Gene symbol Functions include

functions
NRG1 Multiple roles in brain development, synaptic plasticity, and 
 glutamate signalling
DTNBP1 Glutamate releaseDISC -1 Multiple roles in development, cell functioning, and synaptic 
 signalling
PPP3CC Critical molecule for integration of dopamine and glutamate 
DAOA Affects metabolism of the NMDA receptor modulator 
D-serine
COMT Regulation of dopamine function in frontal cortex
NRG1, neuregulin 1; DTNBP1, dysbindin; DISC -1, disrupted in schizophrenia-1; PPP3CC, calcineurin 
Aγ subunit; DAOA, D-amino acid oxidase activator COMT, catechol- O-methyltransferase.4.3.6.2 the neurobiology of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 566
it will probably remain difﬁ  cult to determine in detail the genetic 
contribution to the neurobiology of schizophrenia, given that there are many genes, each of small and complex effects.
(85)
Summary
Signiﬁ  cant progress has been made in understanding the neurobi-

(85)
Summary
ology of schizophrenia over the past decade (Table 4.3.6.2.4). In particular, there is now good evidence for a dopaminergic dys-function, and for structural brain changes that are present at, and in part before, the onset of illness. There is also emerging evidence for several susceptibility genes, accompanied by data suggesting mechanisms by which these genes contribute to the neurodevelop-mental and other pathogenic processes that are thought to lead to schizophrenia. Whilst highlighting the progress, one must also acknowledge that much remains unknown (Table 4.3.6.2.5), and it is a moot point how and when the research advances will impact on the diagnosis, treatment, or prognosis of schizophrenia.

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Table 4.3.6.2.5  Current key questions to be addressed in the 
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X  Are there differing neurobiological substrates for the psychotic, cognitive, 
and negative components of schizophrenia?
X  How do the genes interact with each other, and with the environmental risk 
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Springer, Norwell, MA.4.3.7 Course and outcome of 
schizophrenia and their prediction

The course of schizophrenia is as variable as its symptoms. 
Systematic investigations of course of the psychoses were initiated by Kraepelin who believed that, in the absence of demonstrable brain pathology and aetiology, a common outcome into ‘psychic weakness’ of the clinical syndromes he grouped together as demen-
tia praecox  would provide a validity test for the disease entity. 
Later, Kraepelin revised his claim that the prognosis of dementia praecox was invariably poor and noted that ‘permanent cures’ had occurred in about 15 per cent of his cases.
(1) Subsequent 
longitudinal studies have conﬁ  rmed the striking variability of 
course as one of the salient characteristic of the ‘natural history’ of schizophrenia.
Methodological issues

The large number of studies on the course and outcome of schizophrenia published since the beginning of the twentieth century might suggest that the longitudinal aspects of the disorder are well established and exhaustively documented. Unfortunately, this is not the case since the methodological difficulties that accompany this type of research are complex and few studies have adequately dealt with all the major sources of error and confound-ing, including sample selection, deﬁ  nition of outcome, and diag-
nostic criteria used.
(2,3)
The studies of the course and outcome of schizophrenia comprise 
statistical reports on admissions and discharges, long-term follow-
back studies  (in which the initial features of the cases and the

back studies  (in which the initial features of the cases and the 
course of the disorder are reconstructed retrospectively from admission records), and prospective investigations (in which patients are enlisted at an early stage of the disorder and followed up for a varying length of time). Each design is vulnerable to bias: admission and discharge statistics usually comprise patients at different stages of disease progression; follow-back studies rely on prevalence samples in which chronic cases tend to be over-represented; and prospective studies , though superior to other 
designs, tend to exclude patients who initially have diagnoses other than schizophrenia but are subsequently re-diagnosed as schizophrenic. The methodological issues that need to be consid-
ered in interpreting the results from longitudinal research into

ered in interpreting the results from longitudinal research into 
schizophrenia include the following.
Diagnosis
The use of either ‘broad’ or ‘restrictive’ deﬁ  nitions of schizophrenia 
may result in vastly different samples on which follow-up data are reported. Systems with an inbuilt illness duration criterion, such as DSM-III ,DSM-IIIR , and DSM-IV  which require at least 6 months 
of unremitting symptoms and a decline in functioning, are likely to overselect patients already developing a chronic course. The result would be a greater homogeneity of outcome at the cost of a com-promised representativeness of the sample as regards the range of

569
possible outcomes of schizophrenia. Diagnostic systems which 
emphasize the cross-sectional features of the disorder, such as ICD-10  (which requires 1 month’s duration of clinically character-
istic symptoms) avoid this limitation, possibly at the expense of including some cases of good prognosis that may be aetiologically or pathogenetically different from poor prognosis schizophrenia. However, until aetiology is elucidated, or validating biomarkers are established, the decision as to what constitutes ‘true’ schizophrenia will remain arbitrary. With regard to prognostic studies, less restric-tive diagnostic systems have the advantage that a broad spectrum of outcomes would be available at the end point of prospective observation, allowing for subgroups to be identiﬁ  ed and their 
characteristics related to the initial manifestations of the disorder and various risk factors.
Deﬁ nitions and assessment of course and 
outcome variables

There is no single measure of course and outcome of a complex 
disorder such as schizophrenia. Blanket terms such as ‘recovery’ , ‘improvement’ , or ‘deterioration’ tend to conﬂ  ate substantially 
different aspects of the evolution of the disorder over time. Most investigators today agree that course (comprising the pathways or trajectories of the disorder) and outcome (the net balance of the clinical and functional descriptors at the end point of observation) are multivariate composites. As a minimum, three domains that need not co-vary over time should be independently assessed: symptom severity; functional impairments including cognitive deﬁ cits, and disablement in social and occupational role perfor-

mance. Each one of these can be further articulated into a number of areas or dimensions. In addition, one must consider extrinsic variables such as measures of environmental and treatment-related inﬂ uences on course and outcome, as well as subjective experiences 
commonly described as ‘quality of life’ . Standardized, reliable 
instruments (interviews, inventories, rating scales) are required for the assessment of most variables. Operational deﬁ  nitions  and 
criteria of relapse and remission have been proposed.
(4,5) It should 
not be forgotten, however, that some of the richest sources of infor-mation are the perceptive, in-depth clinical case studies based on personal patient contact over many years. Collectively, such single case observations can generate hypotheses for testing in epidemio-logically designed studies.
Length of follow-up

The evidence from previous research suggests that very different impressions of the course and outcome of schizophrenia would be gained depending on the duration of prospective observation and the degree of control over the inclusion of patients that are comparable in terms age and length of previous illness.
Cohort attrition
In any follow-up study, a proportion of cases will be lost toobservation because of death, migration, refusal of contact, or other reasons for untraceability. Since such loss of subjects islikely to correlate with particular patterns of course and outcome, it is essential to estimate its possible effect (e.g. by statisticalmodelling) on the interpretation of the ﬁ  nal results, especially
if cohort attrition is greater than 15–20 per cent of the original sample.Other aspects of study design

Variation in the sources of recruitment of cases (e.g. any admission to a treatment facility or catchment area sampling), and of infor-mation regarding course and outcome variables (e.g. face-to-face interviews or collateral data from case notes or informants), can obviously inﬂ  uence the results of any follow-up study. In addition, 
subtle variations in study design, such as whether investigators assessing patients’ symptoms and functioning at any point in time are ‘blind’ to data from previous assessments, can bias the ﬁ  nal 
results. Inclusion of a comparison group (e.g. patients with other psychotic disorders) would help evaluate the extent to which any observed patterns of course and outcome are speciﬁ  c to schizo-

phrenia, whereas appropriate controls drawn from the general population can provide reference points for assessing social vari-ables, such as occupational functioning, stressful life events, or habit-related behaviour such as substance use.
Statistical analysis
Longitudinal research poses a number of speciﬁ  c requirements 
with regard to data analysis. Thus, the problem of multiple com-
parisons  is likely to arise when examining the data for signiﬁ  cant

parisons  is likely to arise when examining the data for signiﬁ  cant 
associations; time series, survival, or path analysis may be required when observations are made and recorded at successive time points in the evolution of the disorder; and methods of unconfounding are called for at each step of the analysis of longitudinal data. While no single study up to date has met all the rigorous methodological requirements, a number of studies have succeeded in controlling at least some of the sources of bias and confounding. The results from previous research are, therefore, not strictly comparable in speciﬁ  c detail, but are informative as regards general trends and 
patterns.
The ‘natural history’ of schizophrenia before the 
neuroleptic era
Since the great majority of schizophrenic patients are today receiv-

patterns.
ing pharmacological treatment, current and recent studies may not reﬂ  ect the ‘natural’ course and outcome of the disorder. Studies 
in urban communities in Scotland
(6) and India,(7) and a study in a 
rural community in China(8) estimated the proportions of never

rural community in China(8) estimated the proportions of never 
hospitalized schizophrenic patients at 6.7 per cent, 28.7 per cent, and 30.6 per cent, respectively. About half of the Scottish patients had been prescribed neuroleptics by their general practitioners while the Indian and Chinese patients had been virtually untreated. In all three settings the outcomes of these interesting samples (which presumably approximate the ‘natural’ history of the disor-der) were heterogeneous but, except for a larger proportion of Chinese patients having marked psychotic symptoms, they did not differ much from the outcomes in the treated groups. In a histori-cal study of 70 Swedish patients with ﬁ  rst admissions in 1925, 
lifetime records were retrieved and re-diagnosed in accordance with DSM-III.
(9) None of these patients had received neuroleptics. 
The ﬁ  nal outcome was rated as good in 33 per cent (but no patient

The ﬁ  nal outcome was rated as good in 33 per cent (but no patient 
was considered as completely recovered), as ‘profoundly deterio-rated’ in 43 per cent, and as intermediate in 24 per cent.
A long-term perspective on the course of schizophrenia ove
 successive generations is provided by a meta-analysis of 320 out-come studies on schizophrenia or dementia praecox published between 1895 and 1992 and including a total of 51 800 subjects.
(10)4.3.7 course and outcome of schizophrenia and their prediction

SECTION 4  clinical syndromes of adult psychiatry 570
Overall, about 40 per cent of the patients were reported as improved 
after an average length of follow-up 5.6 years. There was a signiﬁ  -
cant increase in the rate of improvement during the period 1956–1985 compared to 1895–1955, clearly related to the introduction of neuroleptic treatment, but a secular trend towards better outcomes with every successive decade had been present for much longer. Coupled with the virtual disappearance of the most malignant or ‘catastrophic’ forms of schizophrenia resulting in a profound defect state after a ﬁ  rst psychotic episode, or death (‘lethal catatonia’),

these observations suggest that a transition to a less deteriorating course of the disorder had occurred prior to modern pharmaco-logical treatment. Among the factors explaining this shift one should consider improvements in general care, progressive changes in attitudes and hospital regime which occurred in a number of institutions on both sides of the Atlantic in the 1930s and 1940s, as well as heightened expectations that psychosocial measures such as psychotherapy or rehabilitation could result in a cure in some cases.
Long-term prognosis
Results of course and outcome studies published over the last six decades are shown in Table 4.3.7.1. The studies have been selected on the basis of the length of follow-up (>5 years), effective sample size (>50), and intensity of follow-up and assessment to provide a global overview of the long-term course of schizophrenia.Although the studies differ in their design (prospective, follow-

back, or retrospective), their results have much in common.
Manfred Bleuler’s monograph
(11) is the account of an intensive 
study of 208 patients ﬁ  rst admitted in 1942–1943 and personally 
followed up by the author for 22 years or until death. A recent 
re-interpretation of Bleuler’s diagnoses in terms of DSM-IIIR, DSM-IV , and ICD-10 diagnostic criteria concluded that although some 30 per cent of the original cases would today meet criteria for schizoaffective disorder, the distribution of the types of long-term course did not change signiﬁ  cantly.
(12) Another 23-year follow-up 
of 504 patients admitted in 1945–1959 has been completed by Ciompi,
(14) and Huber et al.(15) interviewed 289 surviving patients 
in Switzerland ﬁ  rst admitted between 1900 and 1962 (median 
follow-up length 36.9 years).
Notwithstanding methodological constraints which apply to 
these studies, their ﬁ  ndings are a unique record of what probably

these studies, their ﬁ  ndings are a unique record of what probably 
represents the closest approximation to the ‘natural history’ of schizophrenia. In summary, they indicate the following.
X Lasting recovery (‘complete cure’) occurred in 15 per cent to 
26 per cent of the cases; 43 per cent had either remitted or exhib-ited mild residual abnormalities which did not interfere with their living in the community.
X Forty-four per cent were still in hospital and severe chronic states 
had developed in 14 to 24 per cent.
Table 4.3.7.1  Results of selected course and outcome studies in schizophrenia, 1972–2005
Author Country Sample size Length of 
follow-up 
(years)Proportion good outcome*
Bleuler (1972)(11)Switzerland 208 23 20% Complete remission; 33% mild defect
Tsuang et al. (1979)(13)USA 186 35 46% Recovered or improved signiﬁ  cantly

follow-up 
Ciompi (1980)(14)Switzerland 289 37 20% Recovered; 43% deﬁ  nitely improved
Huber et al. (1980)(15)Germany 502 22 26% Recovered; 31% remission with mild defect
Harding et al. (1987)(16)USA 118 32 62% Recovered or improved signiﬁ  cantly
Ogawa et al. (1987)(17) Japan 140 21–27 31% Recovered; 46% improved
Shepherd et al. (1989)(18) UK 107  5 22% Recovered, no relapse
Johnstone et al. (1990)(19) UK 530  3–13 14% Excellent; 18.5% very good social adjustment
Carone et al. (1991)(20) USA  79  5 17% Complete remission
Marneros et al. (1992)(21) Germany 249 25 Full remission in 24% (‘broad’) or 7% (‘pure’) schizophrenia
Thara et al. (1994)(22) India  90 (ﬁ  rst-onset cases) 10 12% Complete recovery; 62% remission
Mason et al. (1995)(23) UK  67 13 17% Complete recovery; 52% remission

Wieselgren and Lindström (1996)(24) Sweden 120  5 30% Good outcome
Wiersma et al. (1998)(25) Holland  82 15 27% Complete; 50% partial remission
Ganev et al. (1998)(26) Bulgaria  60 16 32% Complete; 5% partial remission
Gureje and Bamidele (1999)(27) Nigeria 120 13 22% Unimpaired (social outcome); 19% some impairment
Finnerty et al. (2002)(28) Ireland  67 (ﬁ  rst-onset cases) 15 35% Complete remission; 46% partial remission
Thara (2004)(29) India  90 (ﬁ  rst-onset cases) 20  6% Complete recovery; 15% clinically stable
Lauronen et al. (2005)(30)Finland  91 (birth cohort members) To age 31 years  4% Complete recovery; 3% partial remission
*Descriptive categories used by the authors.

571
X In 50 per cent to 75 per cent of the patients, a clinically stable 
state set in after the ﬁ  fth year since onset, with no signiﬁ  cant fur-
ther deterioration.
X Remitting course with multiple episodes and full remissions 
characterized 22 per cent of the patients; catastrophic course (rapid onset of chronic deterioration) was observed in 1 per cent to 4 per cent.
X The 20-year suicide rate was 14 per cent to 22 per cent.
Two American studies largely concur with these ﬁ  ndings. In the 
Vermont study,(16) no less than 62 per cent of the cohort had 
achieved signiﬁ  cant improvement or recovery after an average 
length of follow-up 32 years; the corresponding proportion in the Iowa 500 study
(13) was 46 per cent.
The most striking ﬁ  nding from the long-term follow-up studies 
is the high proportion of patients who recover, either completely or with mild residual abnormalities, after decades of severe illness
(31)

(31)
This contrasts with the ingrained image of schizophrenia as an intractable, deteriorating illness that many clinicians tend to adopt on the basis of a limited follow-up horizon and patient samples selected for unfavourable course and treatment response. It is unlikely that the high percentage of recoveries in the long-term studies could be explained by cases of affective illness or brief transient psychoses misdiagnosed as schizophrenia (the retrospective re-diagnosis of cases according to DSM-III criteria in the American studies did not alter signiﬁ  cantly the results). Similarly unlikely

would be the attribution of all the good outcomes to the antipsy-chotic treatment many of these patients received in the later stages of their illnesses, since comparable proportions of improvement of recovery had been reported for patients who never received neuro-leptics.
(32) A tentative conclusion from such follow-up research 
would be that schizophrenia is not an invariably chronic deterio-rating disorder, and that the progression of the disease can be arrested or even reversed at any stage. The causes of such revers-ibility remain poorly understood, but research focusing speciﬁ  cally 
on the recovering cases will undoubtedly provide essential clues for understanding the nature of schizophrenia.
The results of longitudinal studies published in the last decade

The results of longitudinal studies published in the last decade 
generally tend to corroborate the pattern of outcomes outlined by the earlier studies. However, several recent studies suggest a trend of worsening clinical and social outcomes in patients with schizo-phrenia in both developed countries
(28,30)  and developing coun-
tries.(27,29)  A 13-year follow-up of 120 Nigerian patients(27)
reported much higher rates of severe impairment in social and occupational functioning than those found in the same region of the country by follow-up studies in the 1970–1980s.
Patterns and stages of the course of schizophrenia
The marked heterogeneity of the course of schizophrenia can be reduced to a limited number of patterns into which cases tend to cluster over time. In earlier long-term follow-up studies, eight different categories of course have been described by Bleuler
(11)

(11)
and by Ciompi,(14) and 12 by Huber et al.(15) These classiﬁ  cations 
were derived from empirical observation, rather than statistical modelling, and conﬂ  ated into single categories the mode of onset, 
longitudinal aspects such as frequency and duration of psychotic episodes, remissions, and end states. Treating these various aspects of the longitudinal proﬁ  le of the illness as independent dimensions has been recommended.
(19) However, the complexity of statistical 
modelling of the course of schizophrenia is such that the develop-ment of a classiﬁ  cation of course that would be both useful in 
clinical practice and rigorous in a statistical sense may not be easy to achieve. Therefore, a heuristic compromise between these two requirements should, as a minimum, deﬁ  ne operationally and

clinical practice and rigorous in a statistical sense may not be easy to achieve. Therefore, a heuristic compromise between these two requirements should, as a minimum, deﬁ  ne operationally and 
assess separately: (i) the number and duration of discrete episodes of illness; (ii) the predominant clinical features of each episode (e.g. psychotic or affective); (iii) the number and length of remis-sions and their quality (presence/absence of residual negative or deﬁ cit symptoms and signs). By combining these variables, several 
patterns of course have been derived that have found good empiri-cal support in international follow-up studies:
1 single psychotic episode followed by complete remission;2 single psychotic episode followed by incomplete remission;
3 two or more psychotic episodes, with complete remissions 
between episodes;
4 two or more psychotic episodes, with incomplete remissions 
5 continuous (unremitting) psychotic illness.

With some modiﬁ  cations, these longitudinal patterns have been 
incorporated into ICD-10 and DSM-IV as additional descriptors.
Although the components of the course patterns, such as epi-
sode, remission, residual symptomatology, etc. may not represent ‘pure’ dimensions, it is desirable to restrict the deﬁ  nition of pattern 
of course  to clinical variables only, in order to be able to examine 
its correlations with risk factors and predictors, such as premorbid impairments, mode of onset, or social outcomes. Assessing social functioning independently of the clinical pattern of course is criti-cal to the study of illness-environment interactions and the causes of disablement in schizophrenia.
At present it does not seem possible to deﬁ  ne with any precision 
discrete stages  in the progression of schizophrenic illnesses by

discrete stages  in the progression of schizophrenic illnesses by 
using combined clinical and pathological criteria, as in cancer or 
cardiovascular disease. Nevertheless, a ‘softer’ form of staging is feasible since there is on the whole a good agreement between the results of different studies on the general pattern of course in schizophrenia. On the basis of long-term follow-up studies, the lifetime course of schizophrenia can be articulated into a premor-bid phase (from birth to the onset of psychosis), a phase of acute or positive schizophrenic symptomatology, and a residual phase.
(21)
Various sub-stages have been proposed to describe in ﬁ  ner detail 
the pre-onset and early psychosis period.(33,34)  For most practical 
and research purposes, a three-stage classiﬁ  cation of post-onset 
course  has been proposed:(24)
1 an early deteriorating phase (the ﬁ  rst 5–10 years);

2 a middle (stabilization) phase;3 a gradual improvement phase.
This model agrees well with the empirical evidence and could be 
useful in the collection and summarizing of data on individual 
risks and prognosis.
Three prospective investigations initiated by the World Health 
Organization (WHO): the International Pilot Study on 4.3.7 course and outcome of schizophrenia and their prediction

SECTION 4  clinical syndromes of adult psychiatry 572
Schizophrenia  (IPSS);(35,36) the 10-country study on Determinants 
of Outcome of Severe Mental Disorders ;(37) and the study on 
Assessment and Reduction of Psychiatric Disability(38,39) laid the 
ground for a broad-based, cross-cultural evaluation of the course and outcome of schizophrenia. These studies comprise extensive initial and follow-up information on a total of 2736 patients in 16 countries, diagnosed with schizophrenia according to strict and comparable criteria. Identical or closely similar, standardized assessment procedures and instruments were employed, ensuring a high level of comparability across the multiple sites. Results of the WHO 10-country study (pooled data on 1070 patients in all the research sites) are presented in Table 4.3.7.2.
A more recent, transcultural investigation coordinated by WHO, 
the International Study of Schizophrenia  (ISoS) involving 18 
research centres in 14 countries,

(40,41)  achieved tracing 75 per cent 
of cases assessed in the earlier WHO studies referred to above, as well as additional cohorts from mainland China, Hong Kong, and India. Follow-up data were collected on a total of 1633 cases (surviving or dead), and 890 patients were re-interviewed at either 15- or 25-year follow-up since their ﬁ  rst assessment. Key ﬁ  ndings 
from this landmark study are presented in Table 4.3.7.3.
The following general conclusions can be drawn from the 
WHO studies.
1 There is a striking heterogeneity and variability of the course

and outcome of schizophrenia, both across and within popula-tions. Patients with similar clinical and diagnostic characteristics at baseline assessment develop a spectrum of outcomesranging from stable clinical and social recovery after a singlepsychotic episode to chronic unremitting psychosis andsevere impairment. Long-term follow-up studies lend credibility 
to the conclusion that a high proportion (over 30 per cent)of patients meeting the diagnostic criteria for schizophreniahave relatively favourable outcomes.
2 The frequencies of both relapses and remissions tend to increase 
over time: while at 2-year follow-up of the International Pilot Study of Schizophrenia (IPSS)
(35)11 per cent of the patients had

(35)11 per cent of the patients had 
experienced two or more psychotic episodes followed by com-plete remission, and another 18 per cent had two or more epi-sodes followed by residual symptoms and impairments, the 
corresponding proportions at 5-year follow-up were 15 per cent 
and 33 per cent.
(36) These trends are now bolstered by the ﬁ  nd-
ings of the International Study of Schizophrenia (ISoS)(40) which 
found a 48 per cent recovery rate at the 15-year follow-up and 54 per cent at the 25-year follow-up.
3 Regardless of the increasing relapse rate, the cumulative propor-
tion of follow-up time during which patients have psychotic symptoms (as a percentage of the total follow-up time), tends to remain stable or decrease. At the end of the 5-year follow-up, 57 per cent of the patients had experienced a total of less than

9 months of active psychosis; only 22 per cent had been psychotic 
for 45–60 months. At 15-year and 25-year follow-up, 43 per cent 
and 41 per cent, respectively, have been free of active psychotic 
symptoms for the past 2 years.
4 The levels of social impairment assessed at 2 years changed very 
little during the subsequent years of follow-up. Overall, most of the observed change in the clinical state and social functioning of patients between the 2-year follow-up and the 5-year follow-up Table 4.3.7.2  Two-year course and outcome features of 1070 
patients with schizophrenia in the WHO 10-country study
(37)
Course and outcome descriptor % Patients in 
developing 
countries1 
(n = 467)% Patients 
in developed 
countries2 
(n = 603)
Remitting, complete remissions 62.7 36.8

(37)
(n = 603)
Continuous or episodic, no complete remission 35.7 60.9Psychotic <5% of the follow-up 18.4 18.7Psychotic >75% of the follow-up 15.1 20.2No complete remission during follow-up 24.1 57.2Complete remission for >75% of the follow-up 38.3 22.3On antipsychotic medication >75% of the 
 follow-up15.9 60.8
No antipsychotic medication during follow-up  5.9  2.5
Hospitalized for >75% of follow-up  0.3  2.3Never hospitalized during follow-up 55.5  8.1Impaired social functioning throughout 
 follow-up15.7 41.6
Unimpaired social functioning >75% of 
 follow-up42.9 31.6
1 Colombia, India, Nigeria.
2 Czech Republic, Denmark, Ireland, Japan, Russia, United Kingdom, United States.Table 4.3.7.3  Long-term (15- and 25-year) outcome in patient 
cohorts assessed in the International Study of Schizophrenia (ISoS)

Outcome variable Incidence cohorts 
(N = 1171, including 
15-year follow-up of 
the WHO 10-country cohort)Prevalence cohorts 
(N = 462, including 
25-year follow-up of 
373 cases from the WHO IPSS)
Recovered at follow-up  (Bleuler’s criteria)48.1 53.5
Not psychotic in the 
 past 2 years42.8 40.8
GAF-S
1 > 60 54.0 56.7
Working most of past 
 2 years56.8 73.9
GAF-D2 > 60 50.7 60.3
SMR3 (range)  0.00–5.714 1.04–8.885
1 Global assessment of functioning—symptoms scale.
2 Global assessment of functioning—disability scale.
3 Standard mortality ratio.
4 Rochester (0.00), Moscow (1.41), Chandigarh urban (1.88), Prague (2.53), Chandigarh rural 
(3.02), Honolulu (3.13), Nottingham (3.31), Dublin (4.10), Nagasaki (5.71).
5 Soﬁ  a (1.04), Cali (1.31), Madras (1.90), Agra (1.86), Beijing (2.97), Prague IPSS (3.84), 
Mannheim (5.55), Hong Kong (5.76), Groningen (8.88).

573
was towards improvement rather than deterioration. This also is 
congruent with the ﬁ  ndings at 15-year and 25-year follow-up.
5 While the percentage of patients with continuous, deteriorating 
illness was similar across the sites of the WHO studies, there were signiﬁ  cant differences in the proportions of patients who 
achieved symptomatic and social recovery. In this respect, out-come was generally better in the developing countries. This unexpected ﬁ  nding of the ﬁ  rst follow-up of the International 
Pilot Study of Schizophrenia patients,
(35) who had been recruited 
from consecutive hospital admissions with the attendant possi-bilities of a selective bias, was subsequently replicated by the 10-country study which had an epidemiological design and recruited only ﬁ  rst-contact patients from delimited populations.
(37)
The better course and outcome in the developing country areas

(37)
The better course and outcome in the developing country areas 
could not be attributed to any particular subtype of the disorder, e.g. cases of acute onset, since it applied equally to the cases of slow, insidious onset. The main outcome difference across the study areas was in the occurrence and average length of symptom-free remissions. Remissions tended to be more frequent and to last longer in the developing countries. No single factor accounting for this difference could be identiﬁ  ed 
and it is likely that complex interactions between illness and environment are involved that may include both population differences in predisposing genes ,
(42) and environmental or 
cultural factors, such as relative absence of an institutionalized role of ‘the schizophrenic’ ,
(43) less intrafamilial expressed 
emotion  towards the affected family member,(44) or better inte-

gration of the mentally ill person in the domestic economy in traditional rural communities. It should be noted, however, that the long-term WHO follow-up studies include patients whose onset of psychotic illness occurred decades ago, and that increasing social and economic stresses experienced by both rural and urban communities in many developing countries may have eroded the traditional support systems, resulting in worse outcomes, as suggested by several recent studies.
Whether the better outcome of schizophrenia in the develop-
ing countries is ‘transportable’ following migration to othersettings, remains unclear. Data on immigrants treated for ﬁ  rst

ing countries is ‘transportable’ following migration to othersettings, remains unclear. Data on immigrants treated for ﬁ  rst 
episodes of schizophrenia in the United Kingdom suggest that while Asian patients have a lower relapse and readmission rate than British-born Whites, Afro-Caribbean’s show a higher rate.
(45) The marked social and family structure differences 
between the Asian and the Afro-Caribbean immigrant commu-nities suggest that the likelihood of a more benign course in the new setting may depend on the degree to which the immigrant group has retained its traditional values and intra-groupcohesion.
First episode psychosis
The recent focus on early detection and treatment of ﬁ  rst episodes

The recent focus on early detection and treatment of ﬁ  rst episodes 
of psychosis, driven by theoretical considerations and clinical concerns, is supported by evidence suggesting that the courseand outcome of the earliest stages of a schizophrenic illness may have a pathoplastic effect  on its subsequent course. Speciﬁ  cally, the 
period between the ﬁ  rst onset of psychotic symptoms and the 
initiation of treatment ( duration of untreated psychosis, DUP )
has been shown to correlate with increased time to remission and poor response to treatment.
(46,47) Plausible clinical considerations have been proposed in support of the view that the ﬁ  rst episode 
of psychosis represents a critical developmental transition that
may impact the subsequent course of schizophrenia, possibly by inducing neurotoxic alterations in neural networks, thus preparing the ground for chronic illness.
(48) An extension of this mode of

(48) An extension of this mode of 
thinking is the suggestion that a behavioural or pharmacological intervention prior to the onset of psychotic symptoms could delay or prevent the onset of schizophrenia.
(49)
None of these hypotheses has been conclusively tested. However, 
a number of studies focusing on the prodrome  and the earliest 
manifestations of psychosis have highlighted features such as a presymptomatic drop in cognitive performance and social functioning;
(50) early co-occurrence of ‘positive’ and ‘negative’ 
symptoms;(37) as well as a general malleability of such dysfunction 
in response to appropriate behavioural interventions and low-dose, time-limited pharmacological treatment.
(51–53) This suggests

(51–53) This suggests 
that clinical research bridging the gap between statistical investiga-tions of risk factors or antecedents of disease and individual pathways to psychotic illness may have an important role to play in understanding and, ultimately, inﬂ  uencing the development and 
course of schizophrenia.
Prognosis of speciﬁ  c clinical symptoms and syndromes
Longitudinal studies suggest that the characteristic symptoms of 
schizophrenia tend to ‘breed true’ , i.e. only a minority of patients are eventually reclassiﬁ  ed into other disease categories because of 
a signiﬁ  cant and lasting change in the predominant symptoms. 
However, the proportion of cases warranting a re-diagnosis seems to increase with the length of follow-up.
Depression in schizophrenia

In the WHO International Pilot Study of Schizophrenia,(35, 36)  the 
proportion of patients with initial schizophrenic symptomatology who developed non-schizophrenic (mostly affective) episodes in the course of time increased from 3 per cent in the ﬁ  rst 2 years to 
17 per cent at the end of the 5-year follow-up. In contrast, subse-quent episodes with schizophrenic features occurred in less than 10 per cent of the patients with an initial diagnosis of major depres-sion. Depression is the most common non-schizophrenic syn-drome co-ocurring with schizophrenia also in those patients who retain the essentially schizophrenic character of their illnesses. The proportion of patients who develop clear-cut episodes of major depression ranges from 15 per cent during a 5-year follow-up
(54) to

(54) to 
24 per cent during a 12-year follow-up.(55) This is a much higher 
period prevalence than depression in the general population, which 
suggests that mood disorder may be an intrinsic part of the clinical 
spectrum of schizophrenia. Based on such data, a diagnostic rubric of post-schizophrenic depression  has been added to the classiﬁ  ca-
tion of schizophrenia in ICD-10.
First-rank (schneiderian) symptoms
Subjective thought disorder phenomena, such as thought broad-
cast or insertion, passivity (‘replacement of will’) experiences, and particular type of auditory hallucinations (third-person or commenting ‘voices’) were attributed ‘ﬁ  rst-rank’ signiﬁ  cance in the 
differential diagnosis between schizophrenic and affective psycho-ses by Kurt Schneider.
(56) These symptoms are accorded special 
diagnostic weight in the current diagnostic criteria of both ICD-10 4.3.7 course and outcome of schizophrenia and their prediction

SECTION 4  clinical syndromes of adult psychiatry 574
and DSM-IV . Although Schneider explicitly disclaimed any partic-
ular prognostic value for the ﬁ  rst-rank symptoms, they have a 
strong tendency to recur in the course of schizophrenia. In the WHO 10-country study, patients with one or more ﬁ  rst-rank 
symptoms on the initial examination had a three-fold increased risk of recurrence of such symptoms in subsequent episodes compared to patients with no first-rank symptoms at initial examination.
(37)
Prognosis of schizophrenia subtypes
The evidence that each of the ‘classic’ subtypes of schizophrenia is associated with a characteristic pattern of course is generally weak but surprisingly good for some of the subtypes. Consistent differ-ences have been reported between paranoid ,hebephrenic , and 
undifferentiated  schizophrenia (diagnosed according to DSM-III) 
on a long-term follow-up of 19 years.
(57) Paranoid schizophrenia

(57) Paranoid schizophrenia 
tended to have a remittent course, and to be associated with less disability, in contrast to hebephrenia which had an insidious onset and poor long-term prognosis. Undifferentiated schizophrenia occupied an intermediate position. In the WHO International Pilot Study of Schizophrenia,
(35) four alternative groupings of the ICD-9 
subtypes were tested by a discriminant function for differences with regard to six course and outcome measures. Clear discrimina-tion was achieved between simple and hebephrenic schizophrenia grouped together, on the one hand, and the schizoaffective subtype on the other. However, the comparison of simple and hebephrenic schizophrenia with paranoid schizophrenia resulted in a considerable degree of overlap.
Better discrimination has been claimed for groups of patients 
diagnosed according to the criteria of Leonhard.

(58) A 5–13 years 
follow-up study of 178 patients admitted with a diagnosis of schizophrenia and re-diagnosed according to the Leonhard’s criteria as systematic schizophrenia , atypical (unsystematic) 
schizophrenia, cycloid psychosis , or reactive psychosis
(59) resulted 
in marked outcome differences on blind assessment. While only 10 per cent of the cases in the two schizophrenia groups were judged to have ‘recovered’ , the corresponding proportion in the cycloid and reactive psychoses group was 38 per cent. Conversely, the proportions of ‘unimproved’ cases were 49 per cent and 3 per cent.
The question whether good prognosis, remitting schizophrenia 
with an acute onset is a separate subtype that could be distinguished symptomatologically was addressed in the WHO 10-country study
(37) by comparing 274 patients with an initial ICD-9 diagnosis

(37) by comparing 274 patients with an initial ICD-9 diagnosis 
of acute schizophrenic episode and 752 patients with other schizo-phrenia subtypes. The group of acute cases tended to be younger and had a lower male/female ratio, but was no different from the rest of the schizophrenic patients with regard to initial symptomatology. This argues against acute schizophreniform  ill-
ness being a discrete syndrome, outside the clinical spectrum of schizophrenia.
The course and outcome data on schizoaffective  disorders seem 
to support their placement within the broad category of schizo-phrenia. A retrospective and prospective study of 150 schizoaffec-tive patients and 95 bipolar affective patients
(60) established general

(60) established general 
similarities between the two groups but the schizoaffective cases were less likely to achieve a full remission and more likely to devel-op a residual state (in 57 per cent compared to 24 per cent inthe bipolar group). An intermediate outcome between that of schizophrenia and bipolar affective disorder is a common ﬁ  nding 
in schizoaffective disorders.
Predictors of course and outcome

A wide range of variables have been explored as possible predictors of course and outcome in schizophrenia: (i) socio-demographic characteristics; (ii) features of the premorbid personality and premorbid functioning; (iii) family history of psychiatric disorder; (iv) history of past psychotic episodes and treatments; (v) sub-stance use; (vi) characteristics of the onset; (vii) features of the initial clinical state and treatment response; and (viii) variables related to brain morphology and neurocognitive functioning. Many predictors have been independently replicated by different investigators and there is reasonable agreement on the general direction of their effects. However, deﬁ  nitions of both the indepen-
dent (predictor) and the dependent (outcome) variable tend to vary across studies, and the statistical methods employed range 
from basic descriptive statistics (e.g. x per cent of the patients with

from basic descriptive statistics (e.g. x per cent of the patients with 
characteristic y developed outcome z) to complex statistical models 
with capacity to quantify the independent contribution of individ-ual variables to a speciﬁ  ed outcome.
Table 4.3.7.4 lists the best predictors of the 2-year outcome in 
the WHO 10-country study
(37) and Table 4.3.7.5 summarizes the 
ﬁ ndings about predictors of 15-year outcome for the subset of 
participants in the WHO 10-country study who were re-examined as part of the International Study of Schizophrenia.
(40) Apart from 
the variable ‘setting’ (i.e. research centre), which is a proxy for an unspeciﬁ  ed number of local area features ranging from population

the variable ‘setting’ (i.e. research centre), which is a proxy for an unspeciﬁ  ed number of local area features ranging from population 
genetic background to the multiple facets of ‘culture’ , the mode of onset of symptoms (acute versus insidious), drug abuse, and premorbid psychosocial functioning were the best predictors of the duration of psychotic episodes, achievement of remission, and social outcome at 2-year follow-up. Importantly, the total time with psychotic symptoms during the ﬁ  rst 2 years post-onset emerged 
as the best predictor of 15-year outcome, highlighting the potential importance of interventions aiming to contain and minimize active psychosis during this critical stage.
Limitations of clinical prediction

The explanatory power of any predictor in schizophrenia (in terms of accounting for a proportion of the outcome variance) varies depending on sample size, setting, homogeneity of patient groups, and measurement error, but generally tends to be limited (rarely exceeding 30 per cent of the outcome variance). This suggests that no single background or premorbid characteristic of the person, and no clinical symptom or sign among the initial manifestations of the disorder, is strongly associated with its prognosis in the longer-term. Similarly to the genetic epidemiology of schizophrenia, where non-shared environmental inﬂ  uences account for a greater 
amount of variance than the shared environment, person-speciﬁ  c, 
emergent life events or changes in the mental state may have a similar or even greater impact on the outcome as the initial or pre-morbid predictors. Indeed, variables such as negative symptoms

emergent life events or changes in the mental state may have a similar or even greater impact on the outcome as the initial or pre-morbid predictors. Indeed, variables such as negative symptoms 
have been shown to gain in predictive power if they are assessed 
two or more years after the onset, or after the patients have received 
adequate treatment. The predictive capacity of other variables, for 
example, mode of onset, or a high index of expressed emotion, tends to become attenuated in the course of time. Thus, there is

575
no ﬁ xed set of predictors of the course and outcome of schizophre-
nia, but rather a number of prognostic indicators which allow a judgement to be made about the probability of one or another type of course over a limited time period (usually not exceeding 5 years).
Short-term predictors
There is good agreement between different studies on the factors that help predict a relapse of psychotic symptoms after a period of stabilization or remission. By and large, the best predictor of relapse in the short-term remains the withdrawal of antipsychotic medication, usually due to non-compliance.
(61) Heavy cannabis 
use has been shown to be associated with an increased risk of relapse in a dose-response relationship.
(62) Other factors, such as 
stressful life events(63) and expressed emotion  (EE) within the 
family,(44) have attracted considerable interest, both as independent 
predictors and as modiﬁ  ers of the effects of pharmacological treat-

ment. A high expressed emotion index, assessing a key family member’s emotional over-involvement with, and concomitant criticism of the patient, has been found to be a reliable short-term predictor of psychotic relapse. However a limitation of the method is that it is only applicable to situations of intensive daily interac-
tion between a patient and a carer (typically a family member) which may not be the case for many people with schizophrenia living in hostels or marginal accommodation. Moreover, the cross-cultural validity of the expressed emotion index still remains to be established.
(64)
Medium- and long-range predictors
In ﬁ rst-episode cases, male sex, single marital status, premorbid

(64)
In ﬁ rst-episode cases, male sex, single marital status, premorbid 
social withdrawal and insidious onset have been shown to be relatively robust predictors of a poor outcome in the short- to medium-term (2–5 years), while female sex, being married, having social contacts outside the home, and acute onset predict a rela-tively good outcome. No consistent ﬁ  ndings have been reported 
for age at onset as a predictor, and the long-term follow-up studies do not lend support to the view that an early onset is always associated with a poor prognosis. Similarly, a history of psychotic illness (including schizophrenia) in a ﬁ  rst-degree relative does not 
necessarily predict a worse prognosis. On the contrary, in some studies
(65) patients with a high familial load were found on follow-
up to have a better outcome than ‘sporadic’ cases with no psychotic illness among their ﬁ  rst-degree relatives.

A consistent ﬁ  nding of many studies is that the clinical symp-
toms in either the early, or the advanced stages of schizophrenia, have limited capacity to predict future course and outcome. An exception is the modest predictive power of clear-cut negative symptoms appearing early in the course of the disorder, or when assessed under the conditions referred to above.
The socio-cultural setting , i.e. a developing country or a devel-
oped country, was found to be among the best predictors of 2-year and 5-year outcome in the WHO studies.
(35,36)  It remained a Table 4.3.7.4  Best predictors of 2-year course and outcome in the 
WHO 10-country study (log-linear analysis of 1078 cases)
Course and outcome variables
Predictor Pattern of 
course Time in 
psychosisRemission/no 
remissionSocial 

Age n.s. n.s. n.s. *
Sex * * ** **Marital status ** *** *** ***Acute versus 
 gradual onset*** *** *** ***
Time since 
  onset (duration 
of untreated psychosis)n.s. n.s. ** ***
First-rank 
  symptoms at 
baselinen.s. n.s. n.s. n.s.
Adjustment in 
 childhoodn.s. n.s. ** ***
 adolescence*** *** ***
Close friends * * *** ***
Street drug use * * *** ***Setting 
  (developing/
developed 
country)*** n.s. *** ***
n.s., Not signiﬁ  cant.
*Signiﬁ  cant at p ≤ 0.05.
**Signiﬁ  cant at p ≤ 0.01.
***Signiﬁ  cant at p ≤ 0.001.Table 4.3.7.5  Best predictors of 15-year outcome in the WHO 
10-country study (stepwise linear regression analysis of 766 cases 
included in ISoS)
Predictor GAF-S1 
(centre 
in the 
analysis)GAF-S (area 
variables in the 
analysis)GAF-D
2 
(centre 
in the

(centre 
in the 
2 
(centre 
in the 
analysis)GAF-D (area 
variables in 
the analysis)
Percentage of time 
psychotic (ﬁ  rst 2 years)** **
Setting (centre) * – * –
Blunted affect at initial 
examination–* –*
National health 
insurance available–– –*
Street drug use – – – *
Family involvement 
in care–– –*
* Signiﬁ  cant at p ≤ 0.05.
– Not signiﬁ  cant or not applicable.4.3.7 course and outcome of schizophrenia and their prediction

SECTION 4  clinical syndromes of adult psychiatry 576
signiﬁ  cant predictor of 15-year outcome in the International Study 
of Schizophrenia.(40) Exactly what factors may be underlying these 
marked cultural differences in the prognosis of schizophrenia remains an unresolved issue.
There is a growing interest in the predictive power of neuro-
cognitive functions , such as verbal memory, working memory, 
processing speed, and sustained attention. Though positive results have been reported from a number of studies, theproportion of variance in outcome measures that could be explained by such factors varies from low 14 per cent
(66) to as 
high as 60 per cent,(67) depending on sample selection, patients’

(66) to as 
high as 60 per cent,(67) depending on sample selection, patients’ 
age, and length of follow-up. Overall, there is increasing evidence that neuro cognitive functioning at the early stages of a schizo-phrenic illness predicts signiﬁ  cantly global psychosocial and occupational functioning in the medium-term. Neurocognition is therefore likely to be an increasingly important target for novel pharmacological and cognitive behavioural interventions in schizophrenia.
Recovery from schizophrenia

There is consistent evidence from longitudinal studies reviewed in this chapter that, notwithstanding the high risk of chronic disabil-ity, loss of developmental potential, and diminished quality of life associated with schizophrenia, there is a non-negligible proportion of people who meet the current diagnostic criteria for the disease but ultimately attain nearly complete recovery and a stable level of psychosocial functioning. The existence of a good outcome subgroup within schizophrenia has been known for a long time and the prevailing view is that it is not an artefact of misdiagnosis. Y et little focused research has been conducted to bring to light the characteristics and predictors of this clinical subpopulation. A retrospective study of 436 people diagnosed with schizophrenia in the United Kingdom
(68) found that over a follow-up period of

(68) found that over a follow-up period of 
6 years, 15.6 per cent had a single psychotic episode with complete remission. A 15-year prospective study of 145 patients in the United States
(69) revealed that up to 25 per cent of DSM-III diagnosed 
schizophrenia patients had ceased on their own accord antipsy-chotic medication since the ﬁ  rst 5 years of follow-up and the 
majority of them had remained symptom-free for the rest of follow-up. Common ﬁ  ndings in these two studies were that the 
non-relapsing, high-functioning patients were characterized by a higher level of premorbid occupational achievement and social competence, were less likely to use street drugs,
(68) had better 
insight and an internal ‘locus of control’ .(69) Further study of the 
implications of such indicators of better prognostic potential and internal resources should advance efforts to design management and treatment strategies reducing the disabling impact of the disorder.

Studies conducted over many decades consistently demonstrate that schizophrenia presents a broad spectrum of possible outcomes and course patterns, ranging from complete or nearly complete recovery after acute episodes of psychosis to continuous, unremit-ting illness leading to progressive deterioration of cognitive performance and social functioning. Between these extremes, a substantial proportion of patients show an episodic course with relapses of psychotic symptoms and partial remissions during which affective and cognitive impairments become increasingly 
conspicuous and may progress to gross deﬁ  cits. Although no less

conspicuous and may progress to gross deﬁ  cits. Although no less 
than one-third of all patients with schizophrenia have relatively benign outcomes, in the majority the illness still has a profound, lifelong impact on personal growth and development. The initial symptoms of the disorder are not strongly predictive of the pattern of course but the mode of onset (acute or insidious), the duration of illness prior to diagnosis and treatment, the presence or absence of comorbid substance use, as well as backgroundvariables such as premorbid adjustment (especially duringadolescence), educational and occupational achievement, marital status, and availability of a supportive social network allow areasonable accuracy of prediction in the short- to medium-term (2–5 years).
One of the most striking aspects of the longitudinal course of

One of the most striking aspects of the longitudinal course of 
schizophrenia is the so-called ‘terminal improvement’ . A relatively high proportion of patients tend to improve substantially with ageing. What determines this long-term outcome is far from clear but the stereotype view of schizophrenia as an invariably progressive, deteriorating disorder does not accord well with the evidence. Similarly, a model of schizophrenia as a static neurode-
velopmental encephalopathy  decompensating post-adolescence 
under the inﬂ  uence of a variety of stressors ﬁ  ts only part of the 
spectrum of course patterns. In a signiﬁ  cant proportion of cases, 
the disorder exhibits the unmistakable features of a shift-like 
process with acute exacerbations and remissions which may

progress to severe deterioration or come to a standstill at anystage. Whether a single underlying pathophysiology can explain the variety of clinical outcomes, or several different pathological processes are at work, remains obscure. It has been suggested that the longitudinal course of schizophrenia should be seen as an open-ended, dynamic life process with multiple, interacting bio-logical and psychosocial determinants. Obviously, such issues cannot be resolved by clinical follow-up studies alone, and require a strong involvement of neurobiological research in prospective investigations of representative samples of cases spanning the entire spectrum of course and outcomes. No such studies have been possible until recently, both because of the technical com-plexity of such an undertaking and because of the tendency to selectively recruit for biological investigations patients from the severe, deteriorating part of the spectrum. Overcoming such limi-tations will be essential to the

and because of the tendency to selectively recruit for biological investigations patients from the severe, deteriorating part of the spectrum. Overcoming such limi-tations will be essential to the uncovering of the mechanisms driv-ing the ‘natural history’ of schizophrenia.

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4.3.8 Treatment and 
management of schizophrenia
Historically, there was no shortage of interventions to ‘treat’ insanity,

Historically, there was no shortage of interventions to ‘treat’ insanity, 
and later, schizophrenia. Most were palliative, barely effective and often barbaric. It was only with the development of antipsychotic drugs and evolution of trial methodology in the 1950s that a new era of care arrived.
With chronic or recurrent psychiatric disorders, ‘treatment’ and 
‘management’ are not strictly synonymous. The former has a narrow, patient-speciﬁ  c and largely symptom  focus, comprising traditional 
medical tools, especially medications, while the latter can be deﬁ  ned 
as encompassing a broader range of targets with techniques less speciﬁ  cally part of traditional ‘medical’ repertoires, including

as encompassing a broader range of targets with techniques less speciﬁ  cally part of traditional ‘medical’ repertoires, including 
psychological, social, and behavioural interventions. In both its ‘treatment’ and ‘management’ aspects, schizophrenia has under-gone a concerted therapeutic assault in the past few years but rather 
than introducing clarity into care, the recent literature might 
indicate that certainties which seemed so recently within our grasp, remain elusive.
Evidence-based medicine (EBM) has had a major impact on 
care recommendations for those suffering from schizophrenia. A number of national and international ‘guidelines’ have been published
(1–3) and the Cochrane database provides reviews on a 
range of relevant issues. This move has been important in smooth-ing out variability in patient care but although inﬂ  uential and 
increasingly endorsed, the trend is not beyond criticism. Guidelines are largely derived from efficacy  data, which may translate

increasingly endorsed, the trend is not beyond criticism. Guidelines are largely derived from efficacy  data, which may translate 
awkwardly to real-life effectiveness , while considering solely the 
‘bottom lines’ of trials masks the qualitative problems inherent to design, execution, and analysis. Furthermore, over-adherence to guidelines diminishes the impact that individual variability  within 
the patient pool makes to optimizing treatment choices while deskilling those charged with care of a complex condition where ‘quality’ requires greater skill than is usually credited to those who do it well.

(chlorpromazine, thioridazine, triﬂ  uoperazine) cannot be bettered.
(4)
Although its conclusions referred speciﬁ  cally to phenothiazines ,
subsequent research justiﬁ  es the generalization of its ﬁ  ndings to 
‘antipsychotics’ , making this elegant study relevant still.
Five main points emerged:
1Antipsychotics produce a signiﬁ  cantly greater improvement in 
patients with acute schizophrenic symptomatology than placebo.This action on the positive (or ‘acute’) symptomatology is the primary class action  and is beyond doubt. Reviewing the ﬁ  rst two 
decades of antipsychotic use, Davis and Garver
(5) found that in 
86 per cent of controlled studies chlorpromazine was superior to placebo and that all 26 trials utilizing more than 500 mg/day 
reported deﬁ  nitely greater beneﬁ  t than placebo. In this dose 
range no trials found only marginal beneﬁ  ts. A similar view can 
be drawn regarding the efﬁ  cacy of licensed second-generation 
antipsychotics.

 LEARNING POINT: The antipsychotic effect of antipsychotic 
drugs (or the magnitude of that effect) is not shared by other 
types of psychotropic agent such as sedatives, is not in need of further replication, and forms a valid basis for classiﬁ  cation.
2Antipsychotics of  (three )different chemical types do not differ in 
efﬁ cacy . The conclusion that all antipsychotics have comparable 
‘acute’ efﬁ  cacy is not to say that clinically there is nothing to 
choose between them. Although sharing a primary class action, antipsychotics encompass diverse pharmacologies that in prac-tice can overshadow the action they share in common. There are therefore many ways of viewing class members apart from the traditional subgrouping by chemical structure—e.g. clinical adverse effect proﬁ  le, subdivided into general  or extrapyramidal

tolerability; pharmacodynamically in terms of potency, receptor-binding proﬁ  le or binding characteristics (‘loose’ or ‘tight’), etc. 
This is a large ‘extended’ family! LEARNING POINT: In choosing an antipsychotic drug 
for ‘acute’ treatment, tolerability not efficacy, is the key consideration.
3A substantial proportion of patients show limited or no response to 
antipsychotic drugs . Overall, 61 per cent of those on active drug 
were considered ‘improved’ to ‘very much improved’ .
(4) It has 
usually been agreed that standard drugs produce a satisfactory response in approximately 60–70 per cent of patients with ‘acute’ schizophrenia, while approximately 6–8 per cent do not respond at all.
(6) However, if one includes placebo response rates a less 
favourable picture emerges, suggesting that signiﬁ  cant beneﬁ  ts 
could be more realistically expected in approximately 40 per cent of patients (Table 4.3.8.1).
 Not all those non-responders could be classiﬁ  ed as ‘treatment

 Not all those non-responders could be classiﬁ  ed as ‘treatment 
resistant’ (this concept, now operationally defined, long post-dated the Collaborative Study), but it does mean that in the mixture of ﬁ  rst episode and relapsed patients presenting in 
routine practice, expectations for ‘acute’ (i.e. ‘positive’) symptom resolution must be realistic  and cannot necessarily be improved 
by increasingly aggressive drug treatments alone.
 LEARNING POINT: While providing a necessary foundation 
for clinical improvement to acute  psychotic symptomatology, 
expectations of antipsychotic drugs on this single domain must be realistic. Treatment objectives should be correspond-ingly broad-based.
4A rapid phase (over the ﬁ  rst week) of improvement is followed by a 
slower, more protracted pattern of improvement (over several weeks).This ﬁ  nding has recently been replicated but with a somewhat

slower, more protracted pattern of improvement (over several weeks).This ﬁ  nding has recently been replicated but with a somewhat 
different interpretation to that traditionally adopted. In a review of placebo-controlled studies, Agid et al.
(7) also found that stan-
dardized ratings of positive symptomatology began to decline in the ﬁ  rst week and improvement was signiﬁ  cantly greater in the 
ﬁ rst 2 weeks of treatment than in the subsequent two. This was 
interpreted as rejecting the conventional view that antipsychotic onset is delayed. In an early clinical test of the dopamine hypoth-esis, Johnstone et al.
(8) compared the two isomers of ﬂ  upenthixol 
(ﬂ upentixol), one a dopamine blocker, the other not. They found 
that antipsychotic efﬁ  cacy between the two groups, although evi-
dent in the ﬁ  rst week, only became signiﬁ  cant  in the third week,

dent in the ﬁ  rst week, only became signiﬁ  cant  in the third week, 
often taken as supportive of the delayed onset hypothesis. A com-promise between these two viewpoints comes from other data from this study, which showed that the ﬁ  rst week of treatment Table 4.3.8.1 Antipsychotic and placebo response rates in 
Antipsychotic Placebo %
Very much improved 16 1 15
Much improved 29 11 18Improved 16 10 6Slightly improved 31 31 0Not improved 6 15Worse 2 33
Data from NIMH Collaborative Study.(4)4.3.8 treatment and management of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 580
was also a time of signiﬁ  cant improvement in non-speciﬁ  c symp-
tomatology, especially anxiety, in those exposed to the antidopa-minergic isomer.
(9)
 LEARNING POINT: While early improvement on antipsy-
chotics may comprise a component of primary efﬁ  cacy, such 
early beneﬁ  ts should be interpreted circumspectly in treat-
ment planning, especially dose modiﬁ  cations, as they may 
reﬂ ect mainly  non-speciﬁ  c changes.
5Patients in placebo arms of antipsychotic drugs trials can —and 
do—show improvements in positive symptomatology . This is a 
standard ﬁ  nding in clinical trials often overlooked in routine 
practice. Non-speciﬁ  c beneﬁ  ts that can accrue from the environ-
ment where treatment is undertaken can contribute to maximiz-ing outcomes.
 LEARNING POINT: Drug effects have a context!Despite their limitations, antipsychotics are unquestionably 
the key element in acute treatment. In a unique study, May et al .

LEARNING POINT: Drug effects have a context!Despite their limitations, antipsychotics are unquestionably 
compared response rates and outcomes in a large group of schizo-phrenic patients randomly assigned to one of ﬁ  ve regimes: indi-
vidual psychotherapy, antipsychotics, individual psychotherapy plus antipsychotics, ECT, and ‘milieu’ therapy (ward environment). Patients who received physical treatments did better with increased rates of discharge, reduced lengths of stay, and decreased need for additional treatments.
(10) Two years after discharge, twice as many 
of those treated with antipsychotics as with psychotherapy were in employment, while in the 3 years post-discharge, drug-treated patients spent less time back in hospital.
(11)
(b) ‘Negative’ features
The issue of whether antipsychotics exert efﬁ  cacy  on negative

(11)
The issue of whether antipsychotics exert efﬁ  cacy  on negative 
schizophrenic features rose to prominence in the 1980s as a result of the implications of Crow’s Type 1/Type 2 hypothesis.
(12) The 
inference of this is that efﬁ  cacy is ‘unlikely’ owing to different 
pathophysiological substrates proposed for ‘positive’ and ‘negative’ states. Controversy has persisted, with claims that whatever the case 
may be for ﬁ  rst-generation drugs, new generation antipsychotics 
do possess this action. Recent reviews, however, have been increas-ingly circumspect.
(13)
One consequences of testing Crow’s proposal was that ‘negative’ 
schizophrenic symptomatology came to be viewed as something ratable cross-sectionally . This was a radical shift for traditionally the 
‘defect state’ was conceptualized as a set of phenomena evident mainly from longitudinal  appraisal, relating to complex behav-
ioural signs  such as psychosocial and occupational functioning.

ioural signs  such as psychosocial and occupational functioning. 
This switch assumed that the varied states that can underlie ‘nega-tive’ presentations can be distinguished using cross-sectional clini-cal means alone. This assumption has never been validated and seems to push at the limits of clinical examination.
A major confound in assessing trial data in this ﬁ  eld is the brady-
kinesia of drug-related parkinsonism, a common, pervasive feature in those exposed to antipsychotics yet one whose boundaries remain poorly deﬁ  ned, especially for its subjective  components.
(14)
Changing to drugs or doses with lower extrapyramidal liability, or

(14)
Changing to drugs or doses with lower extrapyramidal liability, or 
improving psychotic phenomena that may underlie social with-drawal is a therapeutic action of sorts, but hardly addresses the question. Likewise, utilizing elaborate statistics (e.g. path analysis) to support efﬁ  cacy for second-generation antipsychotics ignores 
the fact that the problem is clinical attribution, not analysis.Carpenter and colleagues
(15) raised awareness of this issue by 
emphasizing the varied clinical states that can present ‘negatively’ , thereby introducing a differential diagnosis (Table 4.3.8.2). Furthermore, by emphasizing ‘durability’ in their deﬁ  nition of 
‘deﬁ cit’ syndrome,
(16) they reintroduced a longitudinal component, 
aligning this more with the historical concept of schizophrenic negativity. Interestingly, this group found clozapine’s beneﬁ  ts on 
negative features to be conﬁ  ned to patients who did not conform to 
criteria for ‘deﬁ  cit’ state.
(17)

(17)
One cannot help wondering whether the quest for antipsychotic 
‘therapy’ of negative states has been a wild goose chase, predicated on assessment that was reliable—but lacking validity. This view will be controversial, as will our conclusion that Crow’s hypothesis has not yet been disproven—that it remains to be shown that 
antipsychotics as a class exert any therapeutic beneﬁ  ts on primary 
negative schizophrenic symptomatology.
(c) Cognitive ability
The importance of cognitive deﬁ  cits underlying the overt symp-
tomatology of schizophrenia is being increasingly highlighted. They comprise a valid endophenotype in predisposed individuals, general cognition suffers a decline in the shift to ﬂ  orid illness and 
speciﬁ  c cognitive impairments, especially in executive function and 
memory, may relate to structural changes in speciﬁ  c brain areas.
(18)

(18)
The pharmacological question is whether drug treatments can 
enhance cognitive performance and thereby promote beneﬁ  ts in 
other domains.
Evaluation of cognitive actions of antipsychotics faces major 
methodological problems and findings remain contradictory. Standard antipsychotics initially impair aspects of attention and motor behaviour which improve following continued exposure, though working memory and long-term recall do not appear to be fundamentally affected.
(19) Paced performance tests tend to be 
affected while those that are untimed tend to be insensitive, per-haps reﬂ  ecting subtle motor effects.
(20)
While new generation drugs may be associated with marginally 
less cognitive impairment than standard drugs, data are inadequate for ﬁ  rm conclusions.
(21) In the absence of consistent evidence of

(21) In the absence of consistent evidence of 
differential effects on a range of neuropsychological tests, it has been suggested that measurements of ‘social competence’ may represent a more appropriate target for study.
(22)
Furthermore, in studies evaluating cognitive-enhancing 
agents as ‘add on’ therapy no consistent evidence of utility has emerged.
(21,23)
(d) Non-speciﬁ  c symptomatology
Affective symptomatology is prominent in schizophrenia but the 
efﬁ cacy of antipsychotics on such features has received little attention. Table 4.3.8.2 The classiﬁ  cation of ‘negative’ states in schizophrenia
Primary Authentic schizophrenic state
Secondary Positive symptomatology
Depressed moodExtrapyramidal disorder
 Early dysphoria
 Bradykinesia
Psychosocial isolation
After Carpenter et al.(29)

581
Their utility in the treatment of anxiety  and other manifestations 
of ‘arousal’ in acute episodes of illness has not been systematically addressed and rests largely on clinical wisdom.
There is however, a tradition in Continental Europe of attri-
buting antidepressant  actions to low-dose antipsychotics
(24,25) (e.g. 
ﬂ upentixol, sulpiride l-enantiomer, amisulpride) when they may 
exert preferential actions at presynaptic (autoreceptor) dopaminer-gic sites. Data remain inconclusive but it is unlikely that such an action would be clinically useful, as presynaptic selectivity is lost at doses usually required for antipsychotic efﬁ  cacy.
Depression is a common feature of untreated schizophrenia 
and resolves as positive psychotic phenomena diminish.
(26) This 
probably does not reﬂ  ect an antidepressant action but symptom 
covariation. Of greater concern is what was formerly referred to as the ‘depressogenic’ action of antipsychotics.
(27) This again raises

(27) This again raises 
the difﬁ  culty of distinguishing between similar presentations of 
pathophysiologically different states. Van Putten and May described a dysphoric mood state in antipsychotic-treated patients (‘akinetic depression’),
(28) which resolved following administration of 
anticholinergic. This was most likely a subjective manifestation of bradykinesia.
(e) Behaviour
Behaviour can be variously disturbed in schizophrenia, though is seldom considered other than as part of a global assessment. While certain confrontational behaviours such as hostility, belligerence, and resistiveness do improve with antipsychotics,
(29) this is usually 
attributed to improvement in positive symptoms. There is, however, evidence that certain types of behavioural disorder correlate with negative, not positive, features and may represent a distinct domain of disorder.

(30) It seems likely that certain manifestations of behav-
ioural disorganization represent independent dimensions of pathology with their own, predominantly negative, prognostic implications.
(31)
(f) Maintenance
With mood disorders, ‘relapse’ (exacerbation of an ongoing episode) and ‘recurrence’ (emergence of a new episode) are well-deﬁ  ned. 
In schizophrenia, where full remission of acute symptomatology may not be a realistic treatment goal, the distinction is less clear. As the long-term aim is usually minimizing the likelihood of ﬂ  orid 
exacerbation in a disorder characterized by persisting symptom-atology, the term ‘maintenance’ is preferable to ‘prophylaxis’ .
The efﬁ  cacy of antipsychotic drugs in long-term maintenance of 
schizophrenic illness is beyond doubt.
(32) This applies to ﬁ  rst-episode 
patients and to those who have suffered multiple episodes. Nonetheless, it remains difﬁ  cult to quantify the effect as published

patients and to those who have suffered multiple episodes. Nonetheless, it remains difﬁ  cult to quantify the effect as published 
ﬁ gures vary widely. Reviewing relevant trials (covering variable 
follow-up intervals), Janicak et al. concluded that on average 55 per 
cent of those on placebo relapsed compared to 21 per cent on active medication, providing overwhelming statistical support for the maintenance effect.
(32) In qualiﬁ  cation, maintenance studies tend 
to be biased towards patients who have already shown a degree of response and it is likely that the magnitude of this effect, at least over 12–24 months, is less than trial-based analyses suggest.
A crucial question for clinicians is how long maintenance medi-
cation should be continued. The evidence is clear. Relapse rates have been shown to be similar following cessation in groups main-tained well for differing lengths of time, from months to years.
(33)

(33)
Furthermore, no difference in relapse has been found in those who responded well compared to those whose response was less good.(34)
The implication is that, no matter the duration  or the quality  of 
well-being on antipsychotic maintenance, relapse is inevitable
following discontinuation in those with an established relapsing-remitting illness pattern (i.e. two or more episodes), which com-prise the majority.
Not only is relapse a characteristic inherent to these illnesses, it 
seems so too is time  to relapse. Davis et al . showed that placebo 
relapses plotted over a 2-year period occurred along an exponential line, indicating a constant rate of relapse, calculated from pooled 
data at a steady 11.5 per cent per month.
(35)

(35)
Thus, the clinician’s position is clear—for maintenance of well-
being following second or subsequent acute episodes, ‘long-term’ antipsychotic maintenance means ‘lifelong’ . Should patients decide to discontinue, past experience can offer an invaluable tool in pre-dicting when relapse is likely.
Some patients see long-term maintenance as ‘well-being’ only of 
sorts, in which quality-of-life is unacceptably impaired. In such individuals, targeted intervention , where treatment is focused on 
prodromal relapse symptomatology, has intuitive appeal. Alas, the trial evidence does not support this as a general strategy. No con-trolled studies so far have found advantage in targeted intervention and in a meta-analysis, Davis et al . calculated 25 per cent relapse

rates in those continuously treated, rising to 50 per cent in the targeted group.
(36) While carefully selected individuals, who can 
work with family and psychiatrists, may prefer this approach, a fur-ther potential concern is that intermittent exposure to antipsychot-ics may increase liability to tardive dyskinesia.
(14)
Intermittent treatment is, of course, a feature of poor compliance 
(also known as ‘adherence’ or ‘concordance’), itself perhaps the
major contributor to relapse. In terms of major medical events, antipsychotics have a highly favourable risk:benefit ratio but in terms of medically trivial but unpleasant, intrusive adverse effects, the risk:beneﬁ  t ratio is unfavourable , something often over-
looked. Ensuring a maximally effective and tolerable maintenance 
regime is a joint exercise, from which the doctor cannot be excused.
The evidence that depot formulations enhance compliance is

The evidence that depot formulations enhance compliance is 
strong, if largely indirect. Support comes from ‘mirror image’ stud-ies, where time in hospital is compared prior to and after starting depot. Six such studies were unanimous in showing substantial reductions in time spent in the hospital after switching to depot 
(average reduction: 77.8 per cent).
(36) There is nothing to suggest 
that this reflects additional therapeutic  advantage inherent to 
depots, whose beneﬁ  t lies simply in facilitating regular administra-
tion and objective monitoring of compliance. Long-acting inject-able risperidone (not a ‘depot’ in the traditional sense) has so far received favourable assessment
(37) but it is too early to provide

(37) but it is too early to provide 
head-to-head comparative data with conventionally formulated depots. Dosages are also an important consideration in maintenance, as those compatible with maximizing long-term tolerability and well-being are likely to be considerably lower  than those necessary for 
acute symptom control. However, the data are insufﬁ  ciently clear to 
provide speciﬁ  c guidance. Kane et al. showed that relapse rates were 
signiﬁ  cantly higher in patients receiving ﬂ  uphenazine decanoate in a 
dose of 1.25 to 5 mg two weekly compared to those receiving 25 mg,
(38) yet Baldessarini et al . have calculated that in long-term 
treatment, half-maximal effective doses (ED 50) may be as low as 
one-ﬁ  fth to one-tenth those normally employed.(39) In the absence of 4.3.8 treatment and management of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 582
speciﬁ  cs, general principles must sufﬁ  ce. Kane and colleagues also 
showed that while relapse was more likely on low-dose regimes, neuro-logical tolerability and psy chosocial/qualit y-of-life parameters were 
superior.
(38) Gradual pursuit of the minimal effective dose is all that 
can be recommended. Bearing in mind the exponential pattern of relapses, with a modal point at 3–5 months,
(40) ‘gradual’ should 
equate to decrements at intervals of months , not weeks.
(g) Treatment resistance
The limitations of antipsychotic treatment in schizophrenia have 
been known since the 1960s but the concept of ‘treatment resistance’ only sprang to prominence with publication of the US multicentre clozapine study.
(41) Within an operationally deﬁ  ned framework

(41) Within an operationally deﬁ  ned framework 
of ‘resistance’ (failure to respond to at least two antipsychotics of different chemical type administered in adequate dose for a mini-mum of 8 weeks), Kane et al. showed that 30 per cent of those on 
clozapine improved, while only 4 per cent on chlorpromazine/benztropine did likewise ( P < 0.001).
(41)
This has been interpreted as proving that clozapine possesses 
superior efﬁ  cacy  over standard agents. While this is one interpre-
tation, it is not the only one. In this study, a chlorpromazine:clozapine dose equivalence of 2:1 was assumed, which might have disadvantaged chlorpromazine, allowing the interpretation that clozapine’s advantage lies in its unique neurological tolerability .
However, many other studies have conﬁ  rmed clozapine’s edge in

However, many other studies have conﬁ  rmed clozapine’s edge in 
patients who fail to respond satisfactorily to other antipsychotics and whatever the explanation, this is real added beneﬁ  t. It does not 
mean however, that clozapine is a ‘miracle’ drug. While 30 per cent of such patients improving is welcome, the criteria for ‘improve-ment’ here were modest and subsequent review has failed to show substantial long-term beneﬁ  ts in higher level functioning, such as 
occupational ability.
(42) Overall expectations of clozapine, a poten-
tially difﬁ  cult drug to administer, and for patients to tolerate, must 
be realistic.
Similar beneﬁ  t has been claimed for other second-generation 
antipsychotics. However, there is no conclusive evidence that such 
advantages can be attributed to any other antipsychotic agent.
Management: psychological and psychosocial 
interventions
While nowadays, there is no suggestion that the core intervention

While nowadays, there is no suggestion that the core intervention 
in schizophrenia should be anything but medication, the limitations of medication alone in symptomatic, relapse prevention, and satis-faction/quality-of-life terms have long prompted interest in wider forms of management. Randomized-controlled studies of psycho-logical and psychosocial interventions are complex and expensive to undertake and hold many potential problems—sample representa-tiveness, high drop-outs, appropriateness of controls, ﬁ  delity to the 
intervention, blindness, etc. As a result, there have been many fewer such studies than of drugs, though in recent years new work, evalu-ating especially psychological interventions, has been published.
The major types of intervention include:
XCognitive behaviour therapy
XPsychodynamic psychotherapy
XSocial skills training
XPsychoeducation

support its use, a place in management should be beyond doubt.
(43)
The fact is, however, that doubt does remain. A recent Cochrane 
review(44) found that CBT did not reduce relapse and readmission 
compared to standard care (though it did decrease the risk of staying in hospital) and while it improved mental state over the medium term, after a year these slight beneﬁ  ts had disappeared. 
Continuous measures on mental state did not demonstrate con-sistent effects. Compared to supportive psychotherapy, CBT had no effect on relapse and when combined with a psychoeducational approach, no signiﬁ  cant reduction in readmission rates relative to 
standard care alone could be demonstrated.
While some individual studies have shown impressive results, the

While some individual studies have shown impressive results, the 
powerful advocacy CBT has attracted as adjunctive management in schizophrenia seems, at this stage, disproportionate to the evi-dence base. Studies have been built around fundamental design ﬂ aws, most notably in relation to control conditions, allowing 
some to conclude that CBT can be shown to work only in poorly 
controlled trials and not in well controlled ones.
(45) Even between 
studies showing beneﬁ  t, it is difﬁ  cult to discern what the most 
appropriate target(s) should be and what components ought to comprise an/the ideal CBT package. A further problem, speciﬁ  c to 
assessing CBT in group contexts, is inappropriate data analysis where independence of observations is universally assumed, some-thing group interactions violate, with a resultant increase in Type 1 errors.
(46) While CBT may hold promise, widespread endorsement

(46) While CBT may hold promise, widespread endorsement 
of a resource intensive management would seem premature until more and better designed work reports.
A further application of CBT techniques in psychosis has been in 
enhancing compliance. While compliance therapy ,
(47) combining 
cognitive behaviour and motivational interviewing techniques, has shown promise, it has been insufﬁ  ciently evaluated to support 
robust recommendations. A recent Cochrane review
(48) identiﬁ  ed 
only one study comparing this with non-speciﬁ  c counselling. 
No signiﬁ  cant differences were found in overall ‘non-compliance’ 
rates or in mental state measures, attitudes to treatment, global functioning, or quality of life. Although at 1 and 2 year follow-ups, average number of days in hospital was reduced, this was not statis-tically signiﬁ  cant. This study did not show any effect on insight,

but other work has claimed that improvements can be achieved by short, insight-focused CBT interventions, but at the expense of increasing depression,
(49) an observation also reported with 
non-CBT approaches targeting insight.(50)
Cognitive remediation  (or rehabilitation), in which the desired 
end-point is not symptom reduction per se but improved global  functioning via amelioration of cognitive deﬁ  cits such as 
impaired vigilance, attention, and planning/decision-making, has also been applied in adjunctive management. Once again, while some individual findings are encouraging, data remain inconclusive.
(51)

583
LEARNING POINT: While present evidence does support the 
use of CBT led interventions in adjunctive management of schizo-phrenia, the research is ﬂ  awed and further, well controlled  stud-
ies are necessary to determine a precise role.
(b) Psychodynamic psychotherapy
Unlike Freud, many analysts of the early-mid twentieth century were undaunted in pursuit of psychodynamic understanding of, and management for, schizophrenia but theories were universally unsupported by evidence. When assessed against supportive psy-chotherapy, no advantages could be demonstrated.
(3) While some 
modest revival of interest may be detected, especially amongst advocates of ‘early intervention’ , a recent review provided no support for such revisionism.
(52) Furthermore, May’s study(10,11)
offers a cautionary warning of the potential for harm.LEARNING POINT: Insight-orientated dynamic psychotherapy has no current place in the management of schizophrenia.
(c) Social skills training

As a result of the early age of onset, relapsing nature, and persis-tence of many clinical features, schizophrenia can potently disrupt smooth acquisition and evolution of skills essential for developing mature interpersonal relationships, occupational competence, and independent living. Social  (or life) skills training  evolved in the con-
text of resettlement programmes aimed at discharging long-stay, institutionalized patients but in various forms remain widely prac-tised. It is based on a structured learning-orientated approach to the acquisition of skills relevant to the individual and the demands of his/her environment.
Unfortunately, social skills training is difﬁ  cult to evaluate, as this

Unfortunately, social skills training is difﬁ  cult to evaluate, as this 
has become a ‘blanket term’ covering a wide range of applications and targets. While some studies have focused on rehearsal of acti-vities of daily living, others concentrate on communication and 
conversational skills, and although some view improvement in 
symptoms as the underlying goal, for others the beneﬁ  t lies with 
cognitive ability. Blindness of assessments is a major problem, though can be easily achieved using blinded video techniques. Thus, while individual studies have found improvements in assertiveness, general social competence, and even speed of dis-charge, with beneﬁ  ts extending to a widened social network and 
that generalize, a recent Cochrane review failed to ﬁ  nd conclusive 
evidence of beneﬁ  t.
(53)
Illness self-management  is part of several social skills training

(53)
Illness self-management  is part of several social skills training 
programmes but has been singled out as the focus of specialized techniques, comprising video modelling, role-play, and speciﬁ  c 
problem-solving combined with homework. While promising results have been reported,
(54,55)  this intensive approach requires 
further evaluation.
Vocational training  (or rehabilitation) is not directly dependent 
on social skills training but is related to it. Although the majority of schizophrenic patients end up unemployed (up to 85 per cent in the US; 73 per cent in the UK),
(56) specialist vocational training 
remains a scarce component of long-term illness management in most services. A review
(56) concluded that supported employment
models were signiﬁ  cantly more effective than pre-vocational train-
ing in facilitating competitive employment, the latter being no better

ing in facilitating competitive employment, the latter being no better 
than standard community care. Supported employment was also associated with higher earnings and more hours working per month. It is sobering that even in trial contexts an average of only 34 per cent of individuals in supported employment were actually employed at 18 months, the comparable ﬁ  gure for those who 
received pre-vocational training being 12 per cent.
(56)
LEARNING POINT: Although intuitively sound and generally 
appreciated by patients and families, ‘social skills training’ can 
only be given a ﬁ  rm evidence base with further well controlled 
studies in which individual components of therapy are ‘teased out’ for separate evaluation and speciﬁ  c end-points are genuinely 
blindly assessed.
(d) Psychoeducation

Much of the above comprises an element of ‘education’ in the widest sense but programmes have been advocated in which 
information exchange is the key intention. Psychoeducation  can be 
targeted on the patient to improve outcomes, enhance compliance, and increase knowledge, including on early relapse recognition, thereby contributing to a better sense of well-being. Imparting factual material is also a fundamental component of many family interventions (see below).
In general, patients appreciate sessions in which their illness is 
explained, reinforcing the idea that some understanding is possible in situations which may seem incomprehensible. Furthermore, explaining bizarre experiences and beliefs in illness  terms can help 
de-stigmatize preconceptions they themselves may hold.

Like most psychological and social interventions advocated as 
adjunctive strategies for schizophrenia, ‘psychoeducation’ is not a single procedure with standardized delivery, something that inher-ently limits systematic reviewing. Nonetheless, it has a favourable review in the Cochrane Library,
(57) which found that relapse 
and readmission rates were signiﬁ  cantly reduced (NNT = 9) at 9 to 
18 months. Beyond this however, no effect was found on insight, medication-related attitudes or overall satisfaction with services by patients or families. Thus, while data to date are consistent with some overall  beneﬁ  ts from psychoeducation, those that are proven 
remain few.LEARNING POINT: Psychoeducation, as a blanket concept, is attractive to patients and carers and, because it is brief and inexpensive, to service providers, but its therapeutic  impact may 
be limited. Future studies must deﬁ  ne component elements and

be limited. Future studies must deﬁ  ne component elements and 
address complexities, such as the distinction between knowledge and understanding, and the vulnerability of learned material to degeneration.
(e) Family interventions
The therapeutics of schizophrenia broadened from sufferers to families and carers with the observation that criticism and hostility from a close relative (‘expressed emotion’: EE) was an important determinant of relapse. As families remain the key element of sup-port for most patients, development of positive, constructive ways of helping them provide this has rightly formed a considerable research focus over the past 30 years. With regard to EE, the con-sensus is that reduction reduces relapse risk when combined with maintenance medication.
(58) However, this appraisal is not unani-
mous and the importance of EE reduction is in need of modern systematic review.
Family interventions  have broadened to include not only educa-

tional input about the illness, its consequences and service avail-ability, but also psychosocial interventions aimed at developingan alliance (especially important during first presentations), reducing emotional distress, boundary setting, and instillation of realistic expectations of both patient and services. This component 4.3.8 treatment and management of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 584
heterogeneity again makes straight literature comparisons difﬁ  cult. 
A recently updated Cochrane review(59) reported somewhat more 
equivocal ﬁ  ndings than previously, suggesting that while family 
intervention may decrease relapse frequency, the number needed 
to be treated to prevent an episode of relapse (NNT) had risen from 
six in a previous review to eight. The authors emphasized that some negative studies may have been missed by their search, rendering even this ﬁ  gure tentative. There was clearer evidence of an effect in 
reducing hospital admission (NNT = 8) and a likely  beneﬁ  cial effect 
on compliance (NNT = 7). There was no effect on the tendency of individuals to drop out of care but a likely  improvement in general

on compliance (NNT = 7). There was no effect on the tendency of individuals to drop out of care but a likely  improvement in general 
social impairment and in levels of EE. The effect on  suicide seemed neutral. While this may be taken as an endorsement of family inter-ventions, the reviewers offer a salutary caution, suggesting that interested parties—clinicians, patients, policy makers—‘cannot be conﬁ  dent on the effects of family intervention from the ﬁ  ndings of 
this review’ .
LEARNING POINT: Families generally welcome professional 
input dedicated to them  and their  needs at distressing times such 
as ﬁ rst diagnosis and subsequently, with realization of the impli-
cations. As a quality-of-care issue, such involvement is beyond the beneﬁ  ts trial evaluation can provide. However, in proposing 
what works  therapeutically—and works best —further research 
is necessary to deﬁ  ne speciﬁ  c elements of interventions that

is necessary to deﬁ  ne speciﬁ  c elements of interventions that 
are not only appreciated but that contribute unequivocally to well-being of sufferers and family members.
So—using the evidence —what can be concluded from the above? 
In reviewing psychosocial management strategies advocated for those with schizophrenia and their relatives, two observations emerge. First, is a certain ‘regression to the mean’—the more inter-ventions are studied, the harder it becomes to replicate beneﬁ  ts 
enthusiastically identiﬁ  ed early on. The second might be viewed as 
cynical but is worth stating nonetheless—namely, that in our quest to maximize the care of those with this fell disorder, it has been conclusively established that drugs plus  ‘something’ produces better 
outcomes than drugs alone . What remains unclear is whether

outcomes than drugs alone . What remains unclear is whether 
‘something’ amounts to more than projecting high levels of profes-sionalism and/or a common humanity or whether there is indeed a speciﬁ  c  therapeutic component (or components) to any or all of 
these ‘somethings’ .
It is disappointing that after decades of research such a conclu-
sion is still possible and future studies not only need to address the standardization of component element(s) of psychosocial manage-ment but must establish a supremacy for it/them before psychia-
trists in routine practice and policy makers alike are able to invest 
not simply in services that others ‘like’ but that doctors can conﬁ  -
dently endorse as having ﬁ  rm evidence  of therapeutic beneﬁ  t.
(f) Service organization
The rationale of ‘community care’ in promoting independence and

The rationale of ‘community care’ in promoting independence and 
choice is noble but its implementation has frequently been found wanting. A major thrust in community care management has been the introduction of community mental health teams  (CMHTs), 
comprising a comprehensive range of disciplines that bring both collectivism to decision-making and varied expertise to service delivery. Compared to non-team care, CMHT management does promote a greater acceptance of treatment options but further advantages are hard to identify, though reductions in admission and suicides are possible  beneﬁ  ts.
(60)It has long been clinical experience that not all patients with 
acute psychoses, including schizophrenia, require hospitalization and, although the research base (speciﬁ  cally in relation to schizo-
phrenia) is slender, home treatment  programmes have vocal advo-

cates, partly because of the promise they hold for reduction in costly bed numbers. While patient satisfaction is usually high, early 
quality-of-life beneﬁ  ts may not be sustained and, owing to ongoing 
need for inpatient facilities, cost beneﬁ  ts may be limited long-
term.
(61,62)  These are difﬁ  cult services to organize, require intensive 
stafﬁ  ng and sophisticated multiagency working, and even then, 
staff morale can be hard to sustain.(63) They are highly selective in 
who they accept(64) and may work most effectively for those whose 
family units remain well-integrated and supportive,(65) such as 
adolescents, but doubts spanning all the potential beneﬁ  ts are suf-
ﬁ cient to suggest caution in making empirically based leaps to such 
radical service reorganization in the absence of further data.
The policy of institutional closures that began in most developed

The policy of institutional closures that began in most developed 
countries in the 1960s/1970s did not result in reduced patterns of acute bed usage. In fact, rising  admission rates caused concern that 
day and outpatient care alone were inadequate because of failure to maintain engagement or to meet complex needs. Case manage-ment and a variant, assertive community treatment (ACT), arose as ways of optimizing ongoing service involvement and ensuring coordination and delivery of care appropriate to individual clinical and social needs. Both aim to: maintain patients in contact with services; reduce frequency and durations of admissions; improve outcomes, especially social functioning and quality of life. Case 
management is essentially based on ‘brokerage’ , where an individual

member of the multi-disciplinary team is responsible for assessing needs, developing a care plan, arranging implementation and mon-itoring quality and engagement, and is also involved in an element of delivery. This is now seen as the least robust model and more complex variants have arisen. With ACT, the emphasis lies in team  working.
Systematically reviewed, case management  ensures that more 
people remain in contact with services but with the consequence of increased  admission rates.
(66) Furthermore, rather than shorten-
ing admissions, it may actually increase their duration. There isno evidence that it improves outcomes on any clinical or social variables. Compared to standard community care, patientsreceiving ACT are more likely to remain in contact with services, less likely to be admitted, and spend less time in hospital with other beneﬁ  ts in terms of accommodation, employment, and
satisfaction.

(67) However, mental state and social functioning are 
not improved and with overall costs accounted for, ACT is not less 
expensive. In comparison to case management, ACT has advan-tages in terms of reduced time in hospital but overall there are no cost beneﬁ  ts.
(67) Few other comparisons are possible due to inad-
equate data.
The impression that case management should be dropped and 
ACT ﬂ  ourish(67) is somewhat oversimpliﬁ  ed. The negative appraisal 
of case management as of ‘questionable value’ has been criticized(68)
while the ‘effectiveness’ of ACT seems to rest on the recurrent prob-lems of content and ﬁ  delity of delivery noted in relation to all the 
psychosocial interventions discussed here.LEARNING POINT: Like drugs, organizational structures operate in a social and service development context and what applies to one patient group in one national or local environment might not reap similar beneﬁ  ts in another. Community-based

585
or otherwise, the weakness in the care of those with chronic, 
relapsing-remitting disorders like schizophrenia, characterized by autistic withdrawal and social dislocation, is failure to main-tain engagement with specialist services. Any structure that fosters a proactive approach to engagement while maintaining staff morale is likely to be better appreciated and to provide better outcomes.
Treatment and management principles
The following is based on UK experience and may not translate completely across international borders where local traditions and organizational constraints may modify practice. It is only presented as an outline  of issues to be considered and cannot provide a uni-
versal blueprint for care. As will become apparent, the authors would argue that such ‘blueprints’ do not best serve the interests of patients or the expertise of those implementing care.
Doctors confronted with a patient believed to be acutely psychotic 
must address three preliminary questions:

1Does the patient require admission or can they be managed as an 
outpatient?
 Some of the issues were aired above but from the medical  point 
of view, there are a number of scenarios in which admission remains a priority (Table 4.3.8.3).
2Can the clinical situation be dealt with informally or are compul-
sory legal powers required? This will depend on the thorough risk assessment  that must be a 
part of every examination. This must, of course, include the health  risks, not solely those involving threat. The details of 
implementing compulsory detention for assessment and/or treatment will differ in different jurisdictions.
3What is the best ﬁ  rst step in treatment?
 There is no single ﬁ  rst–line drug for the treatment of acute 
schizophrenic episodes—nor, the authors would suggest, anyﬁ rst-line type of antipsychotic. Guidelines are fairly unanimous in

There is no single ﬁ  rst–line drug for the treatment of acute 
schizophrenic episodes—nor, the authors would suggest, anyﬁ rst-line type of antipsychotic. Guidelines are fairly unanimous in 
recommending ‘atypical’ antipsychotics, especially in firstepisodes, and any recommendation qualifying this requires justiﬁ  cation.
Despite its persistence, the term ‘atypical’ has never attained 
pharmacological  credibility. It rests on a single clinical  parameter—a 
perceived reduction in liability to promote extrapyramidal side-effects (EPS)— quite speciﬁ  cally , drug-induced parkinsonism. The 
problems surrounding a subclassiﬁ  cation based on such a vague 
parameter are multiple (e.g. the boundaries of parkinsonism; inadequacies of rating schedules; discrepancies in dose equiva-lences between trial and comparator agents) making ‘atypicality’ of dubious scientiﬁ  c validity.
(14) Carefully conducted trials, not spon-

sored by industry, have recently raised questions about putative advantages in EPS tolerability, even with high potency comparators such as haloperidol, when appropriate equivalence is used.
(69) With 
quality-of-life parameters no different after up to 1 year, and no detectable patient preference,
(70,71)  objectively it is hard to see 
‘atypicality’ as having any merits beyond product marketing. There is certainly little to support any inherent  value for clinical 
decision-making beyond the fact that new generation drugs extend the options.
However, there is now strong evidence  to challenge the blinkered 
‘algorithmic’ prescribing guidelines can foster, especially in relation to ‘atypical’ antipsychotics. Results of the Clinical Antipsychotic Trials of Clinical Effectiveness (CATIE) study raise important issues about the tolerability profiles of different new generation compounds in relation to ﬁ  rst-generation drugs
(72)

(72)
and challenge cost-effectiveness beneﬁ  ts.(73) These data form part 
of an emerging trend that, we contend, opens up once again the full
range  of antipsychotics—new and old—to consideration as 
treatment options.
An alternative to ‘algorithmic’ practice is to view guidelines as 
providing a framework  only, within which all clinical information 
can be brought to bear in prescribing decisions. This approach takes its cue from drug regulation, where the appropriateness of granting a license is based on an individual risk :beneﬁ  t appraisal .
This is a clinical  judgement, the outcome of which is dependent on 
context  (e.g. not simply adverse effect burden but availability of 
alternatives). Patients, psychotic illnesses and drugs to treat them are each diverse, harbouring far greater differences than the few similarities they share. These diversities should be entered into 
the individual risk:beneﬁ  t appraisal in making prescribing choices.

the individual risk:beneﬁ  t appraisal in making prescribing choices. 
So too should the phase  of illness one is planning for—acute 
through to maintenance—as the risk:beneﬁ  t appraisal may shift 
between these in particular individuals.
Some examples of issues for consideration in individual risk:
beneﬁ  t appraisals are shown in Table 4.3.8.4, but the professional ism 
psychiatry claims can only come from expertise in recognizing and accounting for the many varied possibilities.Table 4.3.8.3 Considerations in relation to admission policies in 
patients with acute schizophrenia
Supporting admission Supporting non-admission
Unstable mental state
 Rapidly extending content
 Variable affectMental state disorder stable/slowly
 evolving
Imperative auditory hallucinations
 To harm self
 To harm othersAbsent/no will to act
Marked affective change
 Suspiciousness, anger
 DepressionAffective change mild/amenable to
 reassurance
Behavioural disturbance
 Disorganization
 Dangerousness

To harm othersAbsent/no will to act
 Commission OmissionMinimal behavioural disturbance/risk
 of harm
Cognitive disturbance
 Lack of insight
 Impaired attention/distractability Inability to comprehend advice
 Hopelessness/suicidal ideationNo barrier to engagement
Inadequate social support
 Living alone Vagrancy/neglectGood social supports
Any (other) reason for 
 non-complianceLikelihood of compliance
Medical state
 Intercurrent physical illness
 Substance misuse/dependencyPhysically ﬁ  t
‘Asylum’ Aversion to inpatient care4.3.8 treatment and management of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 586
Identifying goals and deﬁ  ning structure
The key to avoiding confusion and ‘decision paralysis’ in dealing 
with the complex clinical situations schizophrenia presents is to 
delineate the structure  within which it is hoped to achieve a series 
of treatment/management goals . Although arbitrary, three ‘phases’ 
can be identiﬁ  ed:
XAcute
XPost-acute
XMaintenance
The acute phase
This encompasses treatment during the maximally ﬂ  orid symp-
tomatic period, corresponding to ﬁ  rst presentation or subsequent 
acute exacerbations (Fig. 4.3.8.1). It is characterized by a signiﬁ  cant 
shift to illness , though surprisingly, it remains unclear exactly what 
changes deﬁ  ne this shift.The goals include:
i) control of intrusive, non-speciﬁ  c symptomatology (e.g. anxiety, 
agitation, and especially insomnia);
ii) maximizing safety and well-being of the patient and others by 
containing chaotic, socially damaging behaviours;

iii) engag ing the patient in therapeutic recommendations and 
(mental state permitting) gaining consent for treatment plans;
iv) implementing an appropriate foundation drug regime;
v) stabilizing positive symptomatology;
vi) preventing, or if unavoidable, treating psychiatric emergencies.
The risk:beneﬁ  t appraisal at this early stage is driven by the ﬁ  rst 
four of these, for the ultimate goal of acute phase treatment—stabilization of positive symptomatology—is, as noted, likely to be delayed. It is important not to overlook other goals that can be 
achieved quickly, especially those that can be held up as evidence of progress, such as improved sleep.
These goals may be achieved using a single antipsychotic, 
which is the ideal . In this regard, low potency ﬁ  rst-generation

which is the ideal . In this regard, low potency ﬁ  rst-generation 
drugs, such as chlorpromazine, have appeal because of low cost, extensive usage, wide dose ﬂ  exibility and potent, if rapidly habitu-
ating, sedative properties. Flexible dose studies suggest the majority of responses will be achieved in the range of 500–600 mg/day
(5)
with some suggestion that ﬁ  rst-episode patients may respond at 
lower doses. While low potency drugs have a justiﬁ  ably admirable 
reputation in the treatment of presenting, acute phase symptom-atology, they are not generally ideal as sole long-term treatment in view of the often intrusive effects of lingering sedation. As patients who have experienced beneﬁ  t on a particular regime tend not to 
like changes, and such switches can be clinically problematic because of poor dose equivalence data, chlorpromazine alone is usually best reserved as an initial, short-term strategy.

High potency ﬁ  rst-generation drugs, especially haloperidol, have 
also been widely used, especially in the United States, and while effective, contain a potential problem. High potency drugs are safe and tend to be used in higher doses than low potency ones (in 
one study, 4–6 times the low potency equivalent
(74)). This undoubt-
edly follows from the fact that low potency compounds are inherently dose-limited by anti-autonomic and sedative actions. Unsurprisingly, liberal early use of high potency drugs is associated with higher rates of EPS (dys tonias, akathisia, and parkinso nism).
(14)
Two points should be borne in mind in using high potency ﬁ  rst-

(14)
generation antipsychotics. Firstly, it has been shown in both clinical and functional imaging (PET) studies using D2 occupancy levels that usual minimum effective daily doses of haloperidol lie some-where between 2 and 5 mg.
(75,76) Secondly, even utilizing slightly 
higher doses, EPS need present no greater problems with haloperi-dol than they do with placebo or olanzapine.
(69,75)
Nowadays, most clinicians tend to pursue a new generation drug 
as their ﬁ  rst choice and this does have some practical advantages, 
not least single dosing and orodispersable formulations. However, while most new generation drugs have some sedative properties, these are clinically less prominent than with low potency ﬁ  rst-
generation compounds, so achieving early acute phase goals can be protracted. Furthermore, these drugs usually now come with deﬁ ned protocols relating to starting doses and rate of increments

generation compounds, so achieving early acute phase goals can be protracted. Furthermore, these drugs usually now come with deﬁ ned protocols relating to starting doses and rate of increments 
which do not apply to older drugs. A number of guidelines address Table 4.3.8.4  Individual risk:beneﬁ  t appraisal in the use of 
antipsychotics : examples of some considerations
Presentation Possible Strategies Schedule
‘positive’ or ‘negative’ = 
arousalLow potency standard
(solo treatment)‘diminuendo’
or ‘crescendo’
Prominent non-
speciﬁ  c affective 
symptomatologyLow potency standard
Or
New generation + benzodiazepine 
(potentiation)Rapid ‘crescendo’ to 
tolerance
Marked insomnia New generation + 
benzodiazepine
Or low potency standard‘crescendo’ to 6–8 
hours nocturnal sleep + 
maximum of two hours 
in the day
High risk of psychiatric 
emergencyLow potency standard
(+/- additional 
medication)Slow ‘diminuendo’
Tenuous engagement
Poor past medication 
experiences

in the day
experiences 
(tolerability)Overfamiliarity with 
common regimesNew generation 
(solo treatment)Slow ‘crescendo’
Poor physical health
Overweight 
Family history of CV 
disease High potency standard ‘crescendo’
Middle aged
High CVS risk factorsHigh potency standard Low dose regime 
assessed without change 
over protracted period
Prior or present EPS 
symptomatology‘loose binding’ new 
generation (quetiapine)Slow ‘crescendo’
Established history 
of poor long-term engagement/
complianceLong-acting injectable Ultra-slow ‘crescendo’
‘diminuendo’ = starting with higher doses and tailing down to tolerability
‘crescendo’ = starting with lower doses and building up to tolerability

587
the potential impediment this introduces into achieving acute 
phase goals by recommending the adjunctive use of a sedative drug, 
especially benzodiazepines, to gain early control of intrusive non-
speciﬁ  c symptomatology.(77) While this is sound, there is another, 
more traditional, approach—namely, the addition of a second, 
sedative antipsychotic.
This introduces the issue of polypharmacy, against which the 
literature has long (and rightly) railed. However, notwithstanding 
these many cautions, it might seem more logical to treat non-speciﬁ  c 
symptomatology that is psychotically mediated  with an antipsy-
chotic, even if one’s goals are largely short-term and symptomatic, rather than to introduce a further class of medication whose
beneﬁ  ts will not contribute to the fundamental treatment issue 
(see below) and may cause their own, unrelated problems, includ-
ing behavioural ‘dyscontrol’ . Antipsychotic polypharmacy must

be reviewed regularly, justiﬁ  ed constantly and rationalized when 
possible. The real ‘sin’ of polypharmacy is its persistence in the 
treatment plan ‘by default’ . However, it must be acknowledged 
that behavioural disturbance and non-speciﬁ  c symptomatology 
may be so overwhelming that benzodiazepines may be useful
in order to avoid over-rapid, excessive escalations of antipsychotic 
doses.Fig. 4.3.8.1 Outline plan for treatment/ management of schizophrenia: APD, antipsychotic drug; BDP , benzodiazepine; ACH, anticholinergic; B- Block, ß-blocker; 
Amant, amantadine.
4.3.8 treatment and management of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 588
Even if not introduced as a ﬁ  xed part of early treatment recom-
mendations, prescription of additional antipsychotic on an ‘as required’ (or ‘PRN’) basis is virtually standard practice, allowing nursing staff to intervene at their discretion in the face of escalating symptomatology. This has no trial basis
(78) and although a pragmatic 
solution to inherently unstable situations, must be utilized with discretion. Indications, maximum doses, frequencies, and modes of administration must all be written up separately and unambigu-ously. Such regimes should not be viewed merely as a means of 
‘keeping the peace’ but should be used to inform judgementsabout how far short of practical requirements initial treatmentrecommendation fall, invaluable information to incorporate into each treatment review.
Antiparkinsonian medication should be automatically used with 
higher doses of high potency standard antipsychotics ( =/> 10 mgms

higher doses of high potency standard antipsychotics ( =/> 10 mgms 
haloperiod daily or equivalent)
(69)but not with lower doses or 
other acute phase choices.(14) While anticholinergics reduce the 
risk of acute EPS, only a minority will develop these to a clinically signiﬁ  cant degree and antiparkinsonian drugs will interact with 
antipsychotics to interfere with their actions. These drugs have their own proﬁ  le of antimuscarinic effects which can be minimized 
by choosing the most M1-selective compounds (e.g. biperiden, procyclidine) should be used.
(14)
A further point relates to goal (iii) above. Patients are often more 
experienced psychopharmacologists than their doctors! In decid-ing treatment regimes in those with past histories, be advised by the patient. Medications in which they have conﬁ  dence should 
always be one’s ﬁ  rst-line in treating acute relapses.

Prior to the emergence of goal (v) above, monitoring of acutely 
psychotic patients should be frequent , and preferably daily, each 
assessment resulting in a review and, if necessary, modiﬁ  cation of 
the treatment plan. At this stage it is rarely useful to commence formal psychosocial, including educational, programmes with patients, whose cognitive difﬁ  culties will make it hard to engage 
meaningfully, though as part of one’s ongoing dialogue, monitor-ing progress and addressing tolerability and compliance serves an elementary educational purpose. Likewise, one’s interactions with 
families are best restrained to exchange of such basic information 
as the patient will permit (e.g. diagnosis and treatment) and to general support.
The boundary of acute phase of treatment is not rigidly deﬁ  ned,

The boundary of acute phase of treatment is not rigidly deﬁ  ned, 
nor is it necessarily set by major symptomatic reversals. The ultimate aim is ‘stabilization’ , as evidenced by the psychotic process becom-ing less ‘active’ , delusions are recal led as yesterday’ s events,  halluci-
nations become less preoccupying, behaviour more amenable. It may also be that sedation, previously an ally, becomes intrusive and a source of complaint.
The post-acute phase
This is characterized by the re-emergence of stability in both mental state and behaviour. The following goals should be considered:
i) consolidation of clinical improvements;
ii) rationalization of treatment regimes;
iii) resocialization.
The different domains of schizophrenic symptomatology do
not all improve at the same rate and the ﬁ  rst signs of ameliora-

tion should not be taken as evidence that the tide has turned. Global improvements need to mature into speciﬁ  c  improvements 
in particular domains of symptomatology before this can be assumed. Practically, caution is important as over-rapid reductions in antipsychotic dosages before fundamental therapeutic changes have bedded down increases the risk of symptom exacerbation and although there is little evidence on the matter, clinical experience suggests that such very early setbacks are not only demoralizing but more difﬁ  cult to stabilize, requiring higher doses for longer periods 
to recapture previous gains.
Nonetheless, the transition from acute to post-acute phase usu-

ally marks a pivotal point when the balance of appraisal shifts towards the increasing contribution of ‘risk’ to the risk:beneﬁ  t 
assessment. Taking account of this shift is important in maximiz-ing compliance, both short and long term. So an important step of post-acute treatment is about gradual  change towards simplifying 
regimes and maximizing tolerability. The emphasis on ‘gradual’ is 
still important, as over-rapid reductions may be implemented 
ahead of relapse set in train by previous reductions.
In monitoring progress, two issues should be borne in mind. First, 
is a clear impression of the criteria  on which ‘improvement’ are to 
be based. The traditional medical emphasis is on sympto matology, especially positive symptoms, but elimination of all psychotic phe-
nomena, or development of full insight, may be unrealistic goals,

nomena, or development of full insight, may be unrealistic goals, 
particularly in those with established illness. Such attempts usually come at the expense of dose regimes signiﬁ  cantly higher—and with 
correspondingly greater long-term risks—than are necessary for a good quality of life and maximum compliance.
Secondly, patients and families—and those who pay for care—often 
have unrealistic expectations of the timescale over which outcomes can be assessed in acute schizophrenic episodes. Considering both psychopathology and ‘degree’ of remission, Lieberman et al. found 
that the median time to ‘remission’ was 11 weeks, with a mean  time of 
almost 37 weeks—and that, in a ﬁ  rst-episode sample!
(79) Other stud-
ies have produced similar ﬁ  ndings. Even if full ‘remission’ is not the 
goal of acute and post-acute treatment, the relatively protracted tim-escales over which ‘beneﬁ  t’ is to be consi dered must be taken into

goal of acute and post-acute treatment, the relatively protracted tim-escales over which ‘beneﬁ  t’ is to be consi dered must be taken into 
account. There is no evidence that this process can be speeded up by 
escalating doses, which on the contrary, may prolong the situation by introducing unnecessary and intrusive adverse effects.
In this regard, it is worth introducing another concept from past 
studies. In the 1960s a number of authors described a phenomenon of so-called ‘neuroleptic toxicity’ , an apparently paradoxical worsening of mental state with escalating antipsychotic doses.
(80)
In reviewing the dose–response literature, Baldessarini and colleagues suggested that the curvilinear relationships usually found may be explained by increasing extrapyramidal symptom-atology.
(39) Thus, with antipsychotic drugs, while ‘less’ may not 
necessarily be ‘more’ , ‘more is usually less’!
The post-acute phase is the time to introduce appropriate ele-

ments of wider ‘management’ . With the patient, this might include ‘education’ in a more formal sense than hitherto, tackling the nature of the condition and, most importantly, the key role of medication in its treatment, including addressing potential long-term recom-mendations. Regardless of one’s interpretation of the literature on its speciﬁ  c beneﬁ  ts, CBT principles  can be helpful in structuring 
goals and realistic pathways to attaining them and in re-instillinga sense of control and optimism. Families, too, can now moreproductively be brought into formal educational programmes, either singly or in groups.

589
The maintenance phase
The boundary between post-acute and maintenance phases is 
the least defined but is reached when remission—maximal improvements in all major domains of disorder—can reasonably be considered to have occurred. The major goals now are:
i) maximum well-being with minimum adverse effects;
ii) monitoring efﬁ  cacy/effectiveness and tolerability;
iii) continuing or extending rehabilitation and social integration.
Attempts to reduce medication should still be cautious but, 
over the longer term more determined, as one seeks the minimal 
effective dose . As noted, evidence suggests that maintenance regimes

effective dose . As noted, evidence suggests that maintenance regimes 
can be considerably lower than those utilized for acute treatment but this aspect of long-term care is often omitted, perhaps on the basis that no one wishes to ‘rock the boat’ . The result is that maintenance may be facilitated by unnecessarily high doses that, in turn, may impede compliance and increase the liability to long-term adverse effects. These need not be simply neurological but may extend to wider domains of functioning. In the Northwick Park First Episodes study signiﬁ  cantly more patients in the placebo 
group were found to have some clear achievement at 2-year follow-up compared to those on active antipsychotic.
(81)
This ﬁ  nding referred to small numbers but raises the important

(81)
This ﬁ  nding referred to small numbers but raises the important 
question of what are the most satisfactory criteria by which to gauge long-term treatment response-domain-speciﬁ  c criteria or 
global outcomes. Whichever is selected, a second important shift occurs in the risk:beneﬁ  t appraisal in this phase, the goal being the 
active elimination of as many components of ‘risk’ (i.e. side-effects) as possible.
Monitoring neurological tolerability should involve both 
enquiry into subjective  adverse effects as well as examination for 
signs,
(14) the most efﬁ  cient being simply an assessment of the patient 
walking.
The most ambitious aim of maintenance comprises engagement

signs,
walking.
The most ambitious aim of maintenance comprises engagement 
in management geared to attaining the highest possible level of psychosocial and, where possible, occupational functioning for the patient, with carers able to exert the greatest degree of under-standing and coping skills.
Depression, affecting up to 70 per cent of patients in the acute phase, 
tends to remit with the psychosis
(26,82) but as many as one-third 
will develop depression in the maintenance phase. This post-psychotic
(or post-schizophrenic) depression  is likely to be as aetiologically 
heterogeneous as depression in other contexts but has been poorly studied including from a therapeutic perspective. Despite initial pessimism, there is evidence that such mood states respond to tri-cyclic antidepressants
(83) though response is impeded in those

(83) though response is impeded in those 
experiencing residual or recurring psychotic symptoms on low maintenance antipsychotic regimes.
(84)
Negative symptoms are present throughout the course of
schizophrenia but are most likely to raise speciﬁ  c therapeutic issues 
during maintenance. An outline of care options is shown inTable 4.3.8.5.
Prodromes
Some would say the above is far from comprehensive, missing the
key element in the care of schizophrenia nowadays—prevention. In fact, they would argue, by concentrating on recommendations that only apply once the possibility of prevention has passed, we are submitting to traditional therapeutic pessimism, which is 
out-of-step with the optimism of the times.
Prodrome  refers to features that, for any illness, characterize the 
difference between well-being and the state of illness evolution. The patient is not unwell as such but the journey to illness has commenced.
In schizophrenia research, ‘prodrome’ applies to two scenarios.

In schizophrenia research, ‘prodrome’ applies to two scenarios. 
The ﬁ  rst, and perhaps most therapeutically relevant, relates to second 
and subsequent episodes where the clinical team may have a basis for prevention—not of the illness but of the episode (i.e. relapses ). 
The universally negative trial evidence in relation to targeted intervention on early relapse symptomatology has been mentioned but this may be one of those situations in which trial efﬁ  cacy
does not translate well to real-life  situations. Maybe the patients 
selected for such approaches must be ‘targeted’ as much as the symptomatology!
Early symptom recognition should certainly be a key part of the 
education of both patients and their families, a task helped by the fact that as a rule, psychotic episodes run ‘true to form’ . Non-speciﬁ  c

education of both patients and their families, a task helped by the fact that as a rule, psychotic episodes run ‘true to form’ . Non-speciﬁ  c 
and positive features recognized from an earlier episode can be recruited to help identify emergence of subsequent episodes. Especially sensitive, is a change in sleep pattern. As was noted,Table 4.3.8.5 Outline management of ‘negative’ states in 
Question Intervention
1 Is the patient actively psychotic? Start/increase antipsychotics
Reduce levels of stimulation
If not :
2  Is there evidence of
extrapyramidal side-effects?Anticholinergics
AmantadineReduce antipsychotic doses
Switch antipsychotic
 New generation
 Low ptency
If not :
3  Is there evidence of dysphoric
mood?Antidepressants
Anxiolytics
Reduce antipsychotics
Supportive managementSwitch to new-generation 
 antipsychotic
If not :
4 Has psychosis recently resolved? Supportive management
If not :
5 Is the environment impoverished? Resocialization
Rehabilitation
If not :

antipsychotic
If not :
If not :
If not :
6  Is the patient receiving long-term 
medication?Reduce to reasonable maintenance
 dose
Switch to new-generation
Clozapine
Then :
7 Is the problem a ‘deﬁ  cit’ state? Adapt expectations to the patient’s
 capabilities
After Carpenter et al. (29)4.3.8 treatment and management of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 590
if patients have stopped maintenance medication, knowledge of 
thetime  to relapse following previous cessations can be useful in 
high  lighting the ‘critical period’ for subsequent relapse. Such knowledge can be empowering, especially for families and carers and even though trial support is lacking, clinical experience sug-gests it can sometimes be use ful in facilitating swift reintroduction of 
medication or increasing dosages from maintenance to treatment levels.
Relapse prevention through early symptom recognition is not,
however, from where optimism currently springs. This comes from the second application of ‘prodrome’—to the early phase of illness ,
not episode, development.
The ‘ early intervention ’ movement has swelled to an inﬂ  uential

The ‘ early intervention ’ movement has swelled to an inﬂ  uential 
grouping within both the research and policy arms of psychiatry. Its origins lie in a very real concern—the delay that many schizo-phrenic patients experience between the ﬁ  rst signs of illness and 
entry into specialist care. This so-called ‘duration of untreated psy-chosis’ (DUP) is on average 1–2 years but can be longer
(85) and has 
been linked to adversity of outcome, initially on the theoretical basis of some factor mediating neurotoxicity,
(86) though this 
remains unsupported.
While a degree of consensus is possible on what the key elements 
might  comprise, it is as yet impossible to construct a valid model 
of what ‘early intervention’ should  comprise and thereafter to 
measure ﬁ  delity.(87) Nonetheless, its principles have been enthusi-

astically adopted and development of services is government policy in many countries, including the UK. This does however, remain controversial—not at the quality -of-care level, where the aims of 
improving awareness and service access are inherently sound, but at the scientiﬁ  c  level, where evidence supporting improved 
outcomes remains weak.
Recent systematic reviews do point to modest beneﬁ  ts in terms 
of a lower symptom burden and delayed readmission in the short-intermediate term.
(88,89) However, assessment of DUP is

(88,89) However, assessment of DUP is 
invari ably retrospective and although it may be done with reliabil-ity, validity remains suspect. Also, the link may be confounded by, for example, some illness characteristic that mediates both delay in entering services and poor outcome, making interpretation difﬁ cult. The authors’ own work with those at high risk of develop-
ing schizophrenia has pointed to the problems of attributing a ‘prodromal’ psychotic state solely to the emergence of what are tra-ditionally considered ‘psychotic’ symptoms and to the non-speciﬁ  c 
nature of those symptoms that do seem to point to a later formal diagnosis.
(90)
The precise delineation of pathway(s) to illness remains to be 
reﬁ ned to a degree that provides meaningful positive predictive

(90)
reﬁ ned to a degree that provides meaningful positive predictive 
values, thereby avoiding the awkward issue of unnecessary and potentially risky interventions in those whose ‘operationally deﬁ  ned 
normality’ is merely different, not necessarily prepsychotic. Continued investment in ‘early intervention’ services must for the present be driven more by quality-of-care considerations than an evidential base.
Psychiatric emergencies
In dealing with acutely ill psychotic patients, one must always bear in mind the ‘unpredictability factor’ and the potential  for 
aggressive or violent outbursts during acute symptomatic ‘shifts’ . Risk assessment of dangerousness is an imprecise science but should be incorporated into all routine clinical assessments during 
acute phase treatment—and conclusions documented . Caution

acute phase treatment—and conclusions documented . Caution 
should be exercised with patients who are profoundly suspicious, verbally aggressive, resistant to engagement, whose presentation does not allow for comprehensive mental state examination, whose clinical condition is complicated by substance misuse and especially, those who have a past history of assaultive or threatening behaviour.
Principles of wider management are crucial in avoiding  emergency 
situations including the quality of the (ward) environment,staff:patie nt ratios, etc., but even with high levels of vigilance,
pre-emptive plans and good quality management, emergency situations may still occur and must be dealt with decisively.
An outline plan relating to emergency situations is shown in 
Fig. 4.3.8.2.
Poor response and treatment resistance

Where a patient has not responded satisfactorily to an adequate dose (600–800 mg/day chlorpromazine or its equivalent) of anti-psychotic for an adequate period of time (at least 6–8 weeks) they might be considered a ‘poor responder’ but not yet ‘treat-ment resistant’ . Several strategies have been suggested in thissituation.
Antipsychotics
Conventionally, the ﬁ  rst approach is to modify the antipsychotic 
regime by:
1 increasing ﬁ  rst-choice drug to a high-dose schedule (up to 
1000 mg chlorpromazine or its equivalent) for 6–8 weeks;
2 changing to a drug of different chemical type in standard dose 
ranges for 6–8 weeks. (Current research would suggest this should include changes between not just old and new drugs, but in the other direction too);
3 increasing the dose of the second-choice drug to a high-dose 
schedule for 6–8 weeks.

As far as the literature is concerned, it is only when at least one, 
and preferably two, of these steps have failed that the illness should 
be considered ‘treatment resistant’ .
(41)
Despite adoption in routine practice, there is little evidence 
that such manoeuvrings are of themselves effective. More time  may 
still be the crucial factor. There is some evidence that in those switching from a new generation drug, slightly better results may be achieved with risperidone and olanzapine than quetiapine or ziprazidone,
(91) though this might be saying simply that, when tol-
erated, relatively high potency compounds do better than relatively low potency ones.
In clinical practice, especially when external pressures and a

In clinical practice, especially when external pressures and a 
sense of therapeutic confusion have clouded therapeutic goals, antipsychotic doses can escalate ‘by default’ . The issue of ‘neuro-leptic toxicity’ has been mentioned and where high-dose regimes cannot be speciﬁ  cally justiﬁ  ed , it is worth reducing  to average or 
low doses and assessing response. Furthermore, patients showing poor response may beneﬁ  t from addition of a depot , even when 
compliance is not in doubt, possible advantages perhaps relating to adverse pharmacokinetic parameters, such as poor absorption or enhanced metabolism with complex or high-dose oral regimes.

591
Adjunctive medications
Simplifying any complexities that may have entered into treatment 
is a useful strategy when response is poor, such as reducing or stop-ping anticholinergics or other drugs, such as antidepressants, where possible. For kinetic (and possibly dynamic) reasons, such drugs may be acting against the primary therapeutic aim.
While a number of other drugs have been recommended for 
adjunctive treatment of suboptimally responding schizophrenia, there is inadequate evidence to support any of them.
Lithium , independent of its actions on mood, is not ‘anti-
psychotic’
(92) but has been recommended for patients with 
schizoaffective disorders. The evidence is inconclusive and itsuse is best considered empirical in those with prominentaffective symptoms.
(93) There is some evidence of a more rapid 
improvement in symptoms with valproate  augmentation but any 
beneﬁ  ts seem to be transient.(94) This is more than can be said for

beneﬁ  ts seem to be transient.(94) This is more than can be said for 
carbamazepine , whose widespread adjunctive use comes with no 
supporting evidence, though such studies that have been done have 
been small.(95) A recent Cochrane review of the role of lamotrigine
did provide tentative support from small, poor quality studies, sug-gesting that PANSS total and positive and negative subscale scores 
significantly decline on lamotrigine compared to placebo.
(96)
Further work is required before clear recommendations can be made.
At one time, benzodiazepines  were advocated in both the sole and 
adjunctive treatment of schizophrenia, usually in high doses IMPENDING EMERGENCY
Non-drug intervention
Antipsychotic (with sedative properties) orally
 e.g. chlorpromazine 50 – 100mgs (liquid/tabs)
haloperidol 5 – 10mgms
Low-distribution benzodiazepine

e.g. lorazepam 1 – 2mgms•   Talking down
•   Distraction
•   Seclusion
Review 30 –60 minutes
If no response – repeat
Or
If no response or no initial co-operation
•   Talking down
•   Monitor physically
Revise treatment plan – start/increase baseline antipsychotic
If no response – repeat (with higher dose ranges, vital signs permitting)
Revise treatment plan
ESTABLISHED EMERGENCY
•   Monitor vital signs
Review 30 – 60 minutes
Repeat if necessary (vital signs permitting)
* should be used with care in the frail or drug naïveDrug intervention
(Sedative) antipsychotic IM
e.g. haloperidol 5-10mgs
       olanzapine 10mgms
       chlorpromazine 50-100mgms
           (with care in frail elderly or drug
           naïve)

           naïve)
e.g. lorazepam 1-2mgms
sedative antipsychotic IM (as above) in adequate dose
±
Low distribution benzodiazepine as above, administered
separately (depending on severity of incident)
Or
zuclopentixol acetate (Acuphase) IM *
High potency antipsychotic IV
e.g. haloperidol 5 – 10mgmsDrug intervention Non-drug intervention
Fig. 4.3.8.2 Outline plan for treatment/management of psychiatric emergencies.4.3.8 treatment and management of schizophrenia

SECTION 4  clinical syndromes of adult psychiatry 592
(~100 mg/day diazepam). Beneﬁ  ts beyond simple sedation have 
been hard to ﬁ  nd and systematic reviews highlight a small number 
of small, supporting studies.(97) While, as noted, benzodiazepines 
are widely used for treating psy chotically mediated acute behaviou-
ral disturbance, such evidence as there is suggests little difference 
between them and antipsychotics.(97)
Finally, it is worth remembering that the theory behind the intro-
duction of ECT, however ﬂ  awed, related to schizophrenia  and there 
is some evidence to support its use in this condition, especially when rapid global improvement is required and when antipsychotic response has been limited.
(98) However, as in depression, its beneﬁ  ts 
are usually short-lived and do not substitute for an effective long-term medication strategy.
When the patient satisﬁ  es criteria for ‘treatment resistance’ , 
the evidence is, as noted, overwhelming that clozapine  is better

the evidence is, as noted, overwhelming that clozapine  is better 
than any other drug regime.
(41) There is no evidence that any other 
antipsychotic, old or new, shares its edge and in this regard, clozap-ine remains a unique  compound.
Of the psychosocial interventions, only CBT has been suggested 
as possibly helpful in modifying symptoms and improving out-comes in those with ‘treatment resistance’
(99) though further work 
is required to conﬁ  rm these tentative ﬁ  ndings.
The above might be interpreted as inferring that nothing much 
has changed in the treatment and management of schizophrenia, which remains a somewhat pessimistic, even unrewarding, area of therapeutic endeavour: one that is regressing far less moving on. This is far from our experience and the opposite of the impression we wish to create.
Certainly, as far as drug treatments are concerned, no single

Certainly, as far as drug treatments are concerned, no single 
agent or type of agent now seems more satisfactory across the board than any other, but the challenge to ‘atypicality’ as a valid subgrouping of antipsychotics does not limit options—rather it broadens  them, restoring to the treatment repertoire the wide 
range of choices that is the key to individualized care planning. With psychosocial interventions, there does remain more work to be done in proving  absolute efﬁ  cacy and/or effectiveness and the rela-
tive place of each, but in service development and care planning, 
risk:beneﬁ  t appraisal is sophisticated enough to encompass what 
has qualitative value  as well as what is quantitatively proven .
As in all branches of medicine whe re chronic and relapsing disease

is encountered, restoring order on chaos, fostering engagement and lighting a way forward when none may be obvious are for the highest levels of skill, in which evidence-based practice can provide the direction but not yet the speciﬁ  c path. We are fortunate in now 
having available to us the greatest ever range of interventions to 
bring to the care of those who suffer from this most complex and fell disorder. None is comprehensive, all have limitations, but if we wish to provide quality care, care that accounts for the multi-farious manifestations patients present, it is our duty to apply not only the experience of others but of ourselves too.
There is no ‘quick ﬁ  x’ in gaining competence in the treatment and

There is no ‘quick ﬁ  x’ in gaining competence in the treatment and 
management of schizophrenia—and, as yet, no curative ‘holy grail’ either. But there is, more than ever, the opportunity for clinicians to demonstrate real expertise in moulding the range of therapeutics 
now at our disposal. If that is not reason for medical optimism, what is!Further information
There is at present a sense of ‘ﬂ  ux’ in care recommendations 
for those who suffer from schizophrenia and the authors would recommend that some of the articles below should be read  as 
opposed to just ‘referred to’ . Both the American
(2) and the 
Australian(3) guidelines are good examples of present trends in 
this approach, though illustrate the slight differences of emphasis that even ‘evidence’ permits. The CATIE study
(72) is seminal and 
mandatory reading for all those involved in treatment planning (the background to this is presented in Schizophrenia Bulletin
(2003, vol. 29(1))—the CUtLASS study likewise.

(71) Both mark a 
change from simply efﬁ  cacy-based studies to pragmatic, ‘everyday’ 
designs that is likely to intensify. For a background to the impor-tance of absolute doses of standard comparator drugs in efﬁ  cacy 
trials and dose equivalence issues, the studies of Rosenheck et 
al.
(69) and Strakowski et al .(70) are informative, as is that of 
Baldessarini et al.(74) from an earlier period. Crow’s original paper 
on the Type 1/Type 2 dichotomy(12) is historically important
(in the 1980s/1990s, the most cited source of research-testable hypotheses in psychiatry) and helpful in understanding whatwas being proposed and the limitations of subsequent efforts to disprove it.
The authors would contend that behind much of the confusion

The authors would contend that behind much of the confusion 
in the clinical psychopharmacology of the antipsychotic drugs in recent years lurks the long shadow of parkinsonism. This, rather than tardive dyskinesia, has always been the extrapyramidal side-effects issue, partly because of its pervasive presence but also because of its wide and ill-deﬁ  ned boundaries. Those wishing to 
familiarize themselves with more than just the basics are referred to the book by Owens,
(14) one of the few texts to speciﬁ  cally present 
drug-induced parkinsonism in both its subjective and objective components for primarily a psychiatric audience.
Finally, all practicing psychiatrists nowadays should be familiar

Finally, all practicing psychiatrists nowadays should be familiar 
with the address of the Cochrane Library (www.thecochraneli-brary.com) and its Database of Systematic Reviews and should feel comfortable referring to it themselves, not just second-hand. It presents quality syntheses of complex material of relevance to many key areas of psychiatric practice.
 1. National Institute for Clinical Excellence. (2002). Schizophrenia: core 
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 2. Lehman, A.F., Lieberman, J.A., Dixon, L.B., et al. (2004). Practice 
guideline for the treatment of patients with schizophrenia (2nd edn). 
The American Journal of Psychiatry ,161(Suppl. 2), 1–56.
 3. McGorry, P . (2005). Royal Australian and New Zealand College

 3. McGorry, P . (2005). Royal Australian and New Zealand College 
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 4. Cole, J.O. and the NIMH Psychopharmacology Service Center 
Collaborative Study Group. (1964). Phenothiazine treatment in acute schizophrenia. Archives of General Psychiatry ,10, 246–61.
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4.3.9 Schizoaffective and 
schizotypal disorders
Ming T. Tsuang, William S. Stone, 
and Stephen V. Faraone
This chapter focuses on two disorders in the schizophrenia

This chapter focuses on two disorders in the schizophrenia 
‘spectrum’: schizoaffective disorder and schizotypal personality disorder. The emphasis includes the clinical features, classiﬁ  cation, 
diagnosis, epidemiology, aetiology, course, prognosis, and possi-bilities for prevention for each disorder. Some aspects will be underscored to reﬂ  ect controversial issues, such as the heterogene-
ity apparent in each condition. Such issues relate to the accurate classiﬁ  cation of the disorders, which is important for at least two

ity apparent in each condition. Such issues relate to the accurate classiﬁ  cation of the disorders, which is important for at least two 
reasons. First, it is essential to develop reliable and valid diagnostic criteria in order to study the aetiology of the disorders and then utilize that knowledge to develop rational and testable intervention strategies. Heterogeneity adds variance to the process that reduces both the reliability of diagnosis and also the statistical power of experimental designs to detect intervention/treatment effects. 
Second, the development of newer generations of psychopharma-cological treatments holds the promise of matching more appro-
priate and efﬁ  cacious medications with speciﬁ  c syndromes or types

priate and efﬁ  cacious medications with speciﬁ  c syndromes or types 
of symptoms. This trend underscores the importance of differential diagnosis in determining what treatment a patient will receive. Heterogeneity within a diagnostic category complicates achieve-ment of this goal. Another area to be emphasized involves the goal of early interventions, in addition to palliative treatments for these disorders. In contrast, other areas such as the genetic aetiology of schizoaffective disorder and schizotypal personality disorder, and treatments for schizoaffective disorder, will receive less emphasis here, to avoid redundancies with other chapters in this volume. Each disorder will be considered separately, starting with a review of schizoaffective disorder, the more severe of the two spectrum conditions.
Schizoaffective disorder

Schizoaffective disorder afﬂ  icts patients having schizophrenic and 
affective symptoms. Either they have affective symptoms of sufﬁ cient severity and chronicity to exclude an uncomplicated 
diagnosis of schizophrenia, or they show features of schizophrenia that are sufﬁ  cient to exclude an uncomplicated diagnosis of an 
affective disorder.
(1) These types of symptoms may or may not 
occur simultaneously, which underscores the importance of view ing 
the course of the illness longitudinally in addition to its cross-sectional presentation. Symptom clusters that are primarily affec-tive or primarily schizophrenic predominate at different times.
Compared to patients with schizophrenia, patients with schizoaf-
fective disorder often (though not always) demonstrate relatively high levels of premorbid function,
(2,3) but nevertheless show 
signiﬁ  cant premorbid weaknesses in multiple cognitive and clinical

signiﬁ  cant premorbid weaknesses in multiple cognitive and clinical 
functions.(4) Patients with schizoaffective disorder also tend to 
show more identiﬁ  able precipitating events. The nature of the pre-
cipitating stressor may vary widely; for example it may be physical (e.g. recently giving birth or experiencing a head injury) or inter-personal (e.g. change in an important relationship). The clinical course of the disorder is often characterized by a periodic, rapid onset of symptoms that shows a relatively high degree of remission after several weeks or months. As Vaillant pointed out in the 1960s, many of these patients ‘recover’ completely after an episode, and resume their lives at premorbid levels of function.
(5) As will be

(5) As will be 
noted further below, the clinical features of some cases of schizoaf-fective disorder mainly resemble those of schizophrenia, while the features of other cases are more similar to those of bipolar disorder. Regardless of the subtype or variant of the disorder, however, the mortality rate is of special concern. Rates of death due mainly to suicide or accident show elevations in this disorder that are similar to those observed in schizophrenia and in major affective disorders.
(6)
In general, schizoaffective disorder is more common in females 
than in males.(3) The age of onset varies, but tends to be younger 
than that of unipolar or bipolar disorder. Tsuang et al . found
the median age of onset for schizoaffective disorder was 29 years, which was signiﬁ  cantly lower than groups with bipolar or unipolar 
affective disorder, but similar to a group with schizophrenia. 4.3.9 schizoaffective and schizotypal disorders

SECTION 4  clinical syndromes of adult psychiatry 596
Marneros et al .(2) also reported that a median age of onset of 29 
years for schizoaffective disorder was lower than the median age for groups w ith affective disorders (35 years), but reported that it was 
higher than a group with schizophrenia (24 years). In contrast, Reichenberg et al.
(4) reported no differences in the age of ﬁ  rst hos-
pitalization between patients with schizophrenia, schizoaffective disorder, or non-psychotic bipolar disorder. These differences between studies reﬂ  ect differences in both the diagnostic criteria 
employed, and the heterogeneity of the disorder.
The classiﬁ  cation of schizoaffective disorder has always been con-
troversial. Kraepelin reported in 1919 that patients with both affec-tive and schizophrenic symptoms complicated the differential diagnosis due to the ‘mingling of morbid symptoms of both psy-choses’ . Kasanin ﬁ  rst employed the term ‘acute schizophrenic psy-

choses’ in 1933 to describe a group of patients who experienced a rapid onset of emotional turmoil and psychotic symptoms, but who recovered after several weeks or months.
(3) In other words, the 
symptoms appeared similar to schizophrenia during periods of exacerbation, but unlike schizophrenia, they showed a greater tendency to remit between episodes. These features sparked an ongoing debate by the 1960s about the proper classification of schizoaffective disorder. Much of this discussion involved the following proposals:
1 It was a type of schizophrenia (e.g. ‘remitting schizophrenia’);2 It was a type of affective disorder;3 It was a unique disorder that was separate from both schizophre-
nia and bipolar disorder;
4 It reﬂ  ected an arbitrary categorization of clinical symptoms that 
masked a continuum of pathology between schizophrenia and affective illness;
5 It contained a heterogeneous collection of ‘interforms’ between

5 It contained a heterogeneous collection of ‘interforms’ between 
schizophrenia and affective disorder (i.e. symptoms of both disorders).
The last possibility is not mutually exclusive of the ﬁ  rst four; for 
example, one or more variants of schizoaffective disorder may be related closely to schizophrenia, while another may be related more closely to an affective disorder.
The puzzle has yet to be solved. Family and outcome studies pro-
vide useful ways of assessing the relative merits of each of the pos-sibilities outlined above. These approaches are informative and will be reviewed below, although interpretations of such studies are complicated at times by the use of different diagnostic criteria across investigations.
(a) Family studies

Family studies provide an important tool for assessing the relation-ship between disorders. They are a type of genetic study that assumes that related disorders will co-aggregate more frequently among biologically related individuals than they would in the gen-eral population. Thus, a disorder is more likely to be in the schizo-phrenia spectrum if it occurs more frequently among the relatives of schizophrenic patients, compared with suitable controls. Similarly, a disorder is more likely to be in the affective spectrum if it occurs more frequently among the relatives of patients with affective disorders. Evidence for the inclusion of schizoaffective disorder in the schizophrenia spectrum is discussed in greater 
detail elsewhere (see Chapter 4.3.6.1). Only representative ﬁ  ndings 
pertinent to the present discussion about the classiﬁ  cation of 
schizoaffective disorder will be summarized here.
Bertelsen and Gottesman
(7) summarized a series of seven family

(7) summarized a series of seven family 
studies published between 1979 and 1993, using structured diagnos-tic criteria. Analyses of risk to the development of schizophrenia, schizoaffective disorder, and affective disorder in the ﬁ  rst-degree 
relatives of patients with schizoaffective disorder, were included. In all seven studies, the relatives showed a higher risk of develop-ing an affective disorder than of developing schizoaffectivedisorder. In ﬁ  ve of the seven studies the risks of developing
schizophrenia was equal to or greater than the risk of developing schizoaffective disorder. Thus, the relatives of schizoaffective patients showed generally higher risks of developing disorders other than the one with which they were diagnosed. These ﬁ  nd-

ings were consistent with a heterogeneous view of schizoaffective disorder, in which individual cases represented subtypes of either 
schizophrenia or of affective disorder. The ﬁ  ndings were also con-
sistent with the possibility that schizoaffective disorder represents a chance collection of ‘interforms’ between schizophrenia and affective disorder.
These ﬁ  ndings were not consistent with the view that schizoaf-
fective disorder represented a continuum between the other two disorders, because in that case, the rate of schizoaffective disorder in ﬁ rst-degree relatives would have been higher, compared with the 
rates at which these relatives developed schizophrenia or affective disorder. The ﬁ  ndings were also inconsistent with the possibility 
that schizoaffective disorder represented a unique disorder that was independent of either schizophrenia or an affective disorder. In that case, the ﬁ  rst-degree relatives of patients with schizoaffec-

tive disorder should show relatively high rates of schizoaffective disorder itself, but relatively low rates of the other disorders. In the series of studies reviewed by Bertelsen and Gottesman,
(7) the 
morbid risk for schizoaffective disorder itself ranged from 1.8 to 6.1 per cent in ﬁ  rst-degree relatives of patients with schizoaffective 
disorder, which was still higher than the rate observed in the gen-eral population (see the section on epidemiology below). These results, taken together with the higher risks for both schizophrenia and affective disorder, suggest that schizoaffective disorder is a heterogeneous condition. Recent reviews of family studies, including those that considered depressed (i.e. unipolar) and bipolar subtypes, have also underscored both the heterogeneity of schizoaffective disorder, and the controversial nature of its classiﬁ  cation.
(8,9)
(b) Outcome studies
A majority of outcome studies show that schizoaffective disorder

(8,9)
A majority of outcome studies show that schizoaffective disorder 
has a better course than schizophrenia, but a poorer course than 
affective disorder.(10–12) For example, Tsuang and colleagues reviewed 
10 outcome studies reported between 1963 and 1987 that assessed 
patients with either schizoaffective disorder or schizophrenia.(10)
Global, marital, social, occupational, hospital course, and symptom 
dimensions of outcome were measured. In each category, patients 
with schizophrenia showed poorer outcomes. In contrast, their 
review of 11 outcome studies comparing schizoaffective disorder with affective disorder showed that affective disorder was associated with equal or better outcomes on almost all dimensions. Thus, despite differences in methodology and diagnostic criteria,

597
schizoaffective disorder was frequently associated with clinical 
outcomes that were intermediate between those associated with schizophrenia and those related to affective disorder.
Other researchers reported similar ﬁ  ndings. Kendler et al ., for 
example, showed intermediate levels of clinical impairment for schizoaffective disorder in an epidemiological family study.
(13)
Marneros et al . reported on outcomes as part of the Cologne 
Longitudinal study, using modified DSM-III-R diagnoses.(14)
The outcomes were measured by symptoms in ﬁ  ve dimensions

(13)
The outcomes were measured by symptoms in ﬁ  ve dimensions 
(psychotic symptoms, reduction of energetic potential, qualitative and quantitative disturbances of affect, and other disturbances of behaviour) that persisted for at least 3 years. Consistent with the pattern described thus far, poor outcomes in the schizoaffective group occurred at a rate (49.5 per cent of the sample) that was intermediate between those observed in the schizophrenic (93.2 per cent) and affective groups (35.8 per cent), and differed signiﬁ  cantly from both of them. In a more recent study, Jäger et al.
studied 241 patients at the time of their ﬁ  rst hospitalization, and 
then again 15 years later.
(15) Similar to these other examples,

(15) Similar to these other examples, 
schizoaffective subjects presented a clinical picture that was less impaired than the one shown by schizophrenic subjects, but more impaired than the one shown by affective subjects.
While these studies show schizoaffective disorder to have 
intermediate outcomes generally, there are categories in which it resembles schizophrenia or affective disorder more closely. For example, Samson et al .
(10) and Reinares et al .(12) noted that out-
comes for schizoaffective disorder were equivalent to those for affective disorder in several dimensions. Marneros et al ., showed 
that 70 per cent of a schizoaffective group was rated as good or excellent on a measure of social adjustment, which did not differ signiﬁ  cantly from 84 per cent of an affective group who received 
the same rating.
(12) Both groups differed signiﬁ  cantly from a

(12) Both groups differed signiﬁ  cantly from a 
schizophrenic group, however, in which only 44 per cent of the group demonstrated good or excellent outcomes. Moreover, the schizoaffective and affective disorder groups did not differ on a rating scale of psychological impairments (e.g. body language, affect display, conversation skills, and cooperation), although both were rated as signiﬁ  cantly less impaired than the schizophrenic 
group.
Other studies, however, such as Kendler et al .
(13) reported 
similarities between some types of psychotic symptoms in schizoaf-fective disorder and schizophrenia, including the severity of delusions and positive thought disorder, and the frequency of hallucinations. Each of these groups showed higher levels of these symptoms than an affective disorders group. Hizdon et al. showed

recently that individuals with schizoaffective disorder did not differ from individuals with schizophrenia on basic cognitive measures of executive function, memory, and processing speed, although the schizoaffective group did perform better on measures of social cognition.
(16)Reichenberg et al . showed that individuals with 
schizophrenia and schizoaffective disorder who were assessed premorbidly performed similar to each other but lower than indi-viduals who later developed non-psychotic bipolar disorder, on tests of non-verbal and verbal intellectual function, and on tests of basic reading and reading comprehension.
(4)
These overall differences in outcome serve to validate the classi-
ﬁ cation of schizoaffective disorder as a separate syndrome further. 
Its heterogeneity, however, raises the issue of whether such inter-mediate outcomes might reﬂ  ect the mean of a combination of mainly good and mainly poor outcomes. This in turn leads to the

Its heterogeneity, however, raises the issue of whether such inter-mediate outcomes might reﬂ  ect the mean of a combination of mainly good and mainly poor outcomes. This in turn leads to the 
question of whether schizoaffective disorder can be subtyped in a useful and valid manner. If so, are better and worse outcomes associated with different variants of the syndrome?
Vaillant suggested in the 1960s that prognostic indicators, 
including a good premorbid level of adjustment, the presenceof precipitating factors, an acute onset, confusion, the presenceof affective symptoms, and a familial history of affective disorder (or the absence of a schizophrenic history), could predict remission in approximately 80 per cent of cases of ‘remitting schizophre-
nia’ .
(17) The inclusion of affective symptoms and a positive family

nia’ .
(17) The inclusion of affective symptoms and a positive family 
history for affective illness on the list contributed (later) to hypoth-eses that variants of schizoaffective disorder were related toaffective illness and to better outcomes. In contrast, variants associ-ated more with schizophrenic symptoms or family history were associated more with schizophrenia and with relatively pooroutcomes.
(18)
There have been a variety of attempts to subtype schizoaffective 
disorders, based on whether affective or schizophrenic symptoms predominate. The validity of many of these attempts, however, is inconclusive. Bertelsen and Gottesman noted, for example, that at best, relatives of individuals with affective type schizoaffective disorder, or schizophrenic type schizoaffective disorder, showed only trends towards higher rates of affective disorder or schizo-phrenia, respectively.
(7) Similarly, Kendler et al . did not detect

(7) Similarly, Kendler et al . did not detect 
different rates of schizophrenia or affective illness in ﬁ  rst-degree 
relatives of patients with schizoaffective disorder when the patients were subtyped into bipolar and depressive subgroups.
(13) Moreover, 
the subtypes did not predict differences in outcomes.
Conversely, a latent class analysis of psychotic patients from the 
Roscommon study showed that most cases of DSM-III-R schizoaf-fective disorder were categorized in either a bipolar schizomania class ( n = 19), or in a schizodepression class ( n = 13), rather than in 
schizophrenia ( n = 1), major depression ( n = 0), schizophreniform 
(n = 3), or hebephrenia ( n = 3) classes.
(19) Moreover, Reinares et al.
reviewed evidence showing that bipolar and depressive subtypes differed from each other in ways consistent with differences between bipolar and unipolar affective disorders.
(12) For example,

(12) For example, 
the bipolar schizoaffective subtype was associated with more total episodes, more episodes with shorter periods and cycles, and higher frequency of cycles. Higher numbers of cycles were associated with poorer long-term outcomes. Taken together, these studies show at least some recent support for the subtyping of schizoaffective disorder into mainly affective and mainly schizo-phrenic variants.
Other factors associated with poor outcomes include poor 
inter-episode recoveries,
(13) persistent psychotic symptoms in the 
absence of affective features, poor premorbid social adjustment, chronicity, a higher number of schizophrenia-like symptoms,
(20)
and the presence of schizoaffective mixed states.(12)

(20)
The DSM-IV diagnosis of schizoaffective disorder(1) is listed in 
the category of ‘schizophrenia and other psychotic disorders’ . The major feature of the disorder is that, in addition to meeting the clinical criteria for schizophrenia (criterion A), an individual must also experience a major depressive, manic, or mixed episode concurrently. In addition, in the same period of illness, a patient must experience symptoms of psychosis (hallucinations and/or 4.3.9 schizoaffective and schizotypal disorders

SECTION 4  clinical syndromes of adult psychiatry 598
delusions) for a period of at least 2 weeks, in the absence of
mood-related symptoms (criterion B). Nevertheless, affective symptoms must comprise a substantial portion of total duration of the illness (criterion C), and symptoms may not be attributable to either substance use or to a major medical condition (criterion D). Two subtypes of the disorder, including bipolar type and depressive 
type, may be diagnosed.
The criteria for schizoaffective disorder in ICD-10 are similar to 
those in DSM-IV . The essential requirement is that prominent symptoms of affective disorder and prominent symptoms of schizophrenia are present together for at least 2 weeks. Depressive, manic, and mixed subtypes are recognized.
The differential diagnosis includes, most prominently, either

The differential diagnosis includes, most prominently, either 
schizophrenia or affective disorder, which may be differentiated in part by consideration of the longitudinal criteria (criteria B and C), in addition to the cross-sectional criteria (criterion A). The presence of conditions relating to general medication and substance use should also be considered in the differentialdiagnosis.
The epidemiological status of schizoaffective disorder is somewhat uncertain compared with schizophrenia, largely because of dilem-mas related to the diagnosis and classiﬁ  cation of the disorder. 
T o help in the standardization of data from different studies, representative incidence and prevalence estimates will be empha-sized from recent investigations that utilized research diagnostic, DSM-III-R or DSM-IV criteria.
(a) Incidence

Earlier studies showed that new cases of ‘schizomanic’ patients (i.e. manic patients who also demonstrated schizophrenic or paranoid symptoms) numbered approximately 1.7 per 100 000 per year.
(20)
This was less than the 4 per 100 000 per year shown by ‘schizode-
pressive’ patients. The number of schizoaffective cases in this study 
exceeded the number of manic patients, and made up half of the 
number of schizophrenic cases. Since then, Tien and Eaton anal-
ysed data from the Epidemiologic Catchment Area study for three non-overlapping groups with psychotic symptoms.
(21) One of

(21) One of 
these groups comprised individuals with ‘psychotic affective syn-drome’ , which was similar to schizoaffective disorder except that most members of the group (59 per cent) demonstrated psychotic symptoms only in conjunction with a mood disturbance (essen-tially DSM-III-R mood disturbance with psychotic symptoms). The incidence of this disorder was 1.7 per 1000 per year, which was approximately equal to the rate for schizophrenia (2.0 per 1000 per year). Even if the 59 per cent of the group who met the criteria for a mood disorder with psychotic features was excluded, the remain-ing 41 per cent would still comprise a higher incidence ratethan that detected by earlier studies. Differences in samplingprocedures (treated versus non-treated samples) may have contrib-uted to the differences observed in the rates. More importantly,

however, these studies showed that schizoaffective disorder 
occurred at 50 to 85 per cent of the rate of schizophrenia, thusconﬁ  rming that patients with this disorder comprise a clinically 
significant population. One current but long-standing issue involves questions about the temporal stability of incidence rates in schizophrenia-related disorders, as reﬂ  ected by reports of both 
increases and decreases.(b) Prevalence
Until recently, prevalence estimates for schizoaffective disorder relied mainly on samples that were treated in clinics or other psychiatric settings. Because a variety of factors inﬂ  uence the 
decision to enter and remain in treatment, the estimates varied substantially. For example, Okasha reviewed studies that reported rates varying between 2 and 29 per cent.
(8) A recent epidemiological

(8) A recent epidemiological 
study in Finland using 8028 people who were at least 30 years old showed a lifetime prevalence rate of 0.32 per cent for schizoaffec-tive disorder (compared to 0.87 per cent for schizophrenia), which accounted for 10.5 per cent of all psychotic disorders.
(22) This is 
a lower estimate than many earlier studies reported, and likely results from a combination of factors (including a narrowing of diagnostic criteria, and increased utilization of multiple sources of information such as case notes and registers, in addition to inter-view data) that together have improved diagnostic accuracy. Prevalence estimates of putative schizoaffective subtypes remain subject to the same inconsistencies of diagnosis and selection factors that affect schizoaffective disorder itself. Not surprisingly, there is little consensus about whether manic or schizophrenic subtypes predominate (see also Tsuang et al.
(20)).
(c) Review of evidence

(20)).
Treatments for schizoaffective disorder are the same as those for 
schizophrenia and affective disorders alone. As the nature and efﬁ cacy of those treatments are discussed elsewhere, they will not 
be considered here. Rather, this section will focus on management issues related to the need to treat symptoms of both disorders simultaneously, or sequentially.
The authors have found it useful to consider psychopharmacologi-cal treatment in terms of putative subtypes, including affective type schizoaffective disorder and schizophrenic type schizoaffective disorder.
Treatment of schizoaffective disorder, affective subtype, will

Treatment of schizoaffective disorder, affective subtype, will 
include antipsychotic medication (e.g. clozapine, risperidone quetiapine, ziprasidone, or olanzepine), particularly if psychotic symptoms are present. In addition, antidepressants, mood stabiliz-ers (e.g. lithium), or anticonvulsants (e.g. valproate or carbamaze-pine) may be useful with this group. It will be necessary in such cases to weigh the potential risks of such medications, such as elevated toxicity, against the potential beneﬁ  ts.
In schizoaffective disorder, schizophrenic subtype, combination 
treatments may also be more effective than a single treatment. 
We ﬁ  nd, however, that antipsychotic treatments alone may be more 
efﬁ cient in many cases. This is particularly true if affective symp-
toms (i.e. depression) are largely secondary to the experience of having a psychotic condition, and its attendant interpersonal, social, and ﬁ  nancial difﬁ  culties. In these cases, remediation of the

psychotic symptoms may also have the effect of easing the affective problems. For other cases, which include more of a treatment-refractory depression, antipsychotic medication may be augmented with lithium (or another mood stabilizer) or antidepressant medi-cation. Moreover, electroconvulsive therapy may reduce mortality rates in schizoaffective patients.
The authors note that it may be difﬁ  cult at times to distinguish 
the affective subtype from the schizophrenic subtype, especiallyin the presence of ﬂ  orid psychotic symptoms. In these cases,

599
treatment decisions may rest on the presenting symptoms of the 
patient. Treatment during intermorbid periods is in part depen-dent on the presence or absence of psychotic symptoms. As noted above, psychotic episodes in this period are associated withrelatively poorer outcomes, and are likely to require chronicantipsychotic therapy.
Schizotypal personality disorder
Like schizoaffective disorder, schizotypal personality disorder is a complex and chronic condition that includes some, but not all, of the features of schizoaffective disorder and schizophrenia. Most notably, persistent psychosis is not part of the syndrome, although mild forms of thought disorder may occur, such as magical think-ing or ideas of reference (as opposed to delusions of reference, which indicate psychosis). Moreover, brief episodes of psychosis may occur in times of stress, but will not persist.
Schizotypal patients show pervasive deﬁ  cits in social and inter-

personal traits. They often demonstrate aloofness, poor eye contact, affective constriction, and suspiciousness. Consequently, close interpersonal relationships are either avoided, or cause discomfort and anxiety. These individuals usually have few friends. Not surprisingly, schizotypal patients are often deﬁ  cient in accurately 
sensing social cues or affective signals from others. Although they can interact with people when necessary, they often prefer not
to, and do not become more comfortable in social situationswith time.
Schizotypal patients may also show magical thinking, ideas of 
reference, unusual perceptions (e.g. sensing the presence of another person, or that people are talking about them), and/or perceptual illusions (e.g. often perceiving a dimly lit lamp-post as a person). Both their social deﬁ  cits and these cognitive–perceptual problems

contribute to an overall impression of oddness. However, this fea-ture may occur independently of other clinical symptoms,
(23) and 
manifest itself in odd speech or unusual appearance. The oddness or eccentricities evident in these patients are often ego syntonic (i.e. they are not experienced as problems). Moreover, schizotypal patients show deﬁ  cits in attention, long-term verbal memory, and 
executive functions. These deﬁ  cits are qualitatively similar to those 
seen in schizophrenia (and schizoaffective disorder), but like many other clinical manifestations of this disorder, they are quantitatively milder.
Like schizophrenia, schizotypal personality disorder is often

Like schizophrenia, schizotypal personality disorder is often 
evident by early adulthood, but schizotypal traits may be evident in late childhood or adolescence. Once it appears, the disorder tends to show a chronic course, but one that includes periodic exacerba-tions and attenuations of symptoms. A recent study that followed individuals with schizotypal personality disorder for 2 years showed 
that paranoid thoughts and unusual perceptual experiences were 
among the most stable and least malleable DSM-IV symptoms, while the most changeable were odd behaviours and restricted affect.
(24) The former symptoms were thus more trait-like, and 
the latter were more intermittent. Consistent with these ﬁ  ndings, 
the same group also showed that in the course of 2 years (with treatment), 61 per cent of schizotypal patients no longer met DSM-IV diagnostic criteria for the disorder.
(25) With a more
stringent deﬁ  nition of improvement (12 months with two or less

stringent deﬁ  nition of improvement (12 months with two or less 
symptoms meeting criteria), the rate of remission droppedto 23 per cent. These studies show that both the severity and the 
expression of the disorder vary over time and probably, as afunction of treatment.
In contrast to the controversy surrounding the classiﬁ  cation of 
schizoaffective disorder, family, twin, and adoption studies clearly support the view that schizotypal personality disorder is best classi-ﬁ ed in the schizophrenia spectrum.
(26) Nevertheless, it is a complex 
and chronic disorder that in all likelihood, is also heterogeneous. Kendler pointed out that this heterogeneity was at least partly related to the two primary methods used to study the disorder.
(27)
One of these involves the ‘clinical method’ , which identiﬁ  es patients

(27)
One of these involves the ‘clinical method’ , which identiﬁ  es patients 
with mild forms of schizophrenic or psychotic-like symptoms. This type of patient, for example, is often characterized by relatively high levels of positive psychiatric symptoms (e.g. magical thinking and perceptual distortions).
In contrast, the ‘family research method’ identiﬁ  es relatives of 
patients with schizophrenia who have subtle, schizophrenia-like symptoms. Features associated more with familial than with clinical schizotypal personality disorder include a predominance of negative symptoms (e.g. social withdrawal and impairment, and higher levels of anxiety and poor rapport), cognitive impairments (e.g. impaired language comprehension, eye-tracking, and attentional dysfunctions), and elevated rates of schizophrenia and 
related disorders in family members.
(26) Thaker et al. reported that

(26) Thaker et al. reported that 
familial and clinical schizotypal personality disorders were similar on measures of physical or social anhedonia,
(28) and that some 
neuropsychological deficits were also associated with both groups.
(26)
The concept of familial schizotypal disorder is particularly 
important because it may share a common genetic basis with schizophrenia. Paul Meehl ﬁ  rst proposed the term ‘schizotaxia’ to

(26)
important because it may share a common genetic basis with schizophrenia. Paul Meehl ﬁ  rst proposed the term ‘schizotaxia’ to 
describe the genetic vulnerability to schizophrenia, and suggested that individuals with schizotaxia would eventually develop either schizotypal personality disorder or schizophrenia, depending on the protection or liability afforded by environmental circumstances. As the concept evolved, Meehl reformulated it to allow for the possibility that some people with schizotaxia would develop neither schizophrenia nor schizotypal personality disorder. In fact, evidence now shows that the clinical symptoms observed in many non-psychotic, ﬁ  rst-degree relatives of people with schizophrenia 
are similar to those observed in familial schizotypal personality dis-order.
(26) Psychiatric features in such relatives frequently include

(26) Psychiatric features in such relatives frequently include 
an aggregation of negative symptoms that are qualitatively similar to, but milder than, those often cited in schizophrenia.
(29) Positive 
symptoms, however, are usually less evident in these relatives than they are in schizophrenia or in schizotypal personality disorder. Neuropsychological impairments in biological relatives of people with schizophrenia are also qualitatively similar to, but milder than, those seen in people with schizophrenia.
(26) In particular, 
these neuropsychological deﬁ  cits frequently include problems 
in working memory/attention, long-term verbal memory, and concept formation/abstraction.
Faraone et al . recently suggested a reformulation of Meehl’s 
concept of schizotaxia that focuses on these features of negative symptoms and neuropsychological deﬁ  cits.
(26) Unlike schizotypal

(26) Unlike schizotypal 
personality disorder, which occurs in less than 10 per cent of the adult relatives of patients diagnosed with schizophrenia, the basic 4.3.9 schizoaffective and schizotypal disorders

SECTION 4  clinical syndromes of adult psychiatry 600
symptoms of schizotaxia occur in 20 to 50 per cent of adult
relatives, suggesting further that the genetic liability to schizophre-nia does not lead inevitably to schizophrenia, schizotypal personal-ity disorder, or schizoid personality disorder.
The DSM-IV criteria for schizotypal personality disorder include a ‘pervasive pattern of social deﬁ  cits’ and ‘cognitive or perceptual 
distortions’ and behavioural ‘eccentricities’ (criterion A).
(1) At least 
ﬁ ve of nine speciﬁ  c symptoms (e.g. ideas of reference, constricted 
affect, odd behaviour, or appearance) must be present to satisfy this criterion. These symptoms must occur by early adulthood. They must not occur exclusively during the course of four other conditions, including schizophrenia, a mood disorder with psychotic features, any other psychotic disorder, or a pervasive developmental disorder (criterion B).

The differential diagnosis includes a variety of other disorders. 
A key difference between schizotypal personality disorder and schizophrenia, a psychotic mood disorder, or another psychotic condition involves the transient nature of psychotic symptoms in schizotypal personality disorder. It may be distinguished from developmental communication disorders by a lack of compensa-
tory means (e.g. gestures) of communicating, and it may be 
distinguished from autistic or Asperger’s disorders by the relatively greater deﬁ  cits in social awareness and frequent presence of stereo-

typed behaviours in those syndromes. Schizotypal personality disorder may be confused with several other personality disorders, but can be distinguished from them. In particular, it differs from schizoid personality disorder by its pattern of cognitive–perceptual distortions, and by the odd appearance or behaviour shown frequently by schizotypal patients. The pattern of schizotypal symptoms also differs from that manifested in borderline personal-ity disorder, although there are similarities between these condi-tions. Schizotypal personality disorder differs from borderline personality disorder, however, in that psychotic-like symptoms and social isolation are more likely to persist in the absence of affective turmoil, and schizotypal individuals are less likely to display the impulsive and manipulative traits that are often associated with borderline personality disorder.

T o the authors’ knowledge, there continue to be no published incidence studies for schizotypal personality disorder.
(b) Prevalence
A review by Lyons showed that prevalence rates for schizotypal personality disorder in non-clinical samples ranged from0.7 to 5.1 per cent, with a median near 3.0 per cent.
(30) Higher 
rates occurred in clinical samples—2.0 to 64.0 per cent, with a median of 17.5 per cent. More recently, T orgersen et al . reported 
a rate of 0.6 per cent for DSM-III-R in a community sample, which is lower than the rates in studies reviewed by Lyons.
(31)
Similar to recent prevalence rates reported for schizoaffective disorder (described above), more recent studies have tended to show lower rates than earlier studies. In contrast to non-clinical samples, the prevalence of schizotypal personality disorder among the relatives of schizophrenic individuals is as high as10 per cent.
(32)Treatment
(a) Review of evidence

There is, unfortunately, a dearth of outcome studies involving psychotherapy, psychosocial, or psychopharmacological treatments for schizotypal personality disorder. Older published studies often show methodological limitations (e.g. small samples, subjects with mixed diagnoses, inadequate controls, and problems with internal validity), or provide outcome data on only limited aspects of the disorder. Despite these caveats, it is clear that few treatment gains are evident in earlier studies. This is particularly true of studies that utilized psychodynamically oriented psychotherapy, either 
alone or in combination with other treatments (e.g. group therapy 
or art therapy) as the primary treatment modality.
(33) Recent 
evidence for the efﬁ  cacy of psychotherapy for personality disorders 
is more promising, but is limited mainly to other personality disorders.
(34)
Several earlier studies investigated the usefulness of medications

(34)
Several earlier studies investigated the usefulness of medications 
in treating schizotypal personality disorder, although they typically employed small numbers of subjects, combined samples of schizo-typal and borderline personality disorders, and showed little clinical improvement.
(33) Typical antipsychotic drugs, in particular, 
were proposed to reduce positive symptoms or depressed mood in times of acute stress, but the high incidence of adverse side effects discouraged their widespread use at other times, including the more chronic stable (i.e. non-crisis) phases of the disorder. Other types of medication, including fluoxetine, have shown generally non-speciﬁ  c effects of treatment.
Hymowitz et al . administered a low dose of haloperidol, a 
ﬁ rst-generation antipsychotic medication, to 17 outpatients with 
DSM-III diagnoses of schizotypal personality disorder, for 6 weeks.

(35) The initial dose of 2.0 mg was intended to rise to 12.0 mg, 
but side effects prevented increases beyond a mean dose of 3.6 mg. Even with lower doses, 50 per cent of the sample withdrew from the study because of side effects. The 17 subjects who completed 2 weeks of the protocol improved somewhat in ratings of ideas of reference, odd communications, social isolation, and overall functioning.
More recently, Koenigsberg et al. employed a double-blind pro-
tocol to administer low doses of risperidone (0.25 mg/day—2.0 mg/day), a second-generation antipsychotic medication, to 25 patients with DSM-IV schizotypal personality disorder, for 9 weeks.
(36)
Compared to a placebo control group, patients who received risperidone demonstrated signiﬁ  cant reductions in positive and

(36)
Compared to a placebo control group, patients who received risperidone demonstrated signiﬁ  cant reductions in positive and 
negative symptoms, with no difference in dropout rates between groups. These findings are encouraging and consistent with evidence described above that schizotypal symptoms are amenable to change.
(24,25)  Hopefully, ﬁ  ndings like this will stimulate addi-
tional research into pharmacological treatments for this disorder.
Patients with schizotypal personality disorder often view their worlds as odd and threatening places and may require extended courses of treatment. Although trust and rapport with the therapist are often difﬁ  cult to establish in schizotypal personality disorder, 
the therapeutic relationship may be used to mitigate the marked deficits in interpersonal relationships that characterize this syndrome.
(37) The frequent occurrence of paranoia and suspicious-
ness, together with social aloofness and constricted affect, may

601
make exploratory psychotherapeutic approaches less effective than 
supportive cognitive behavioural therapies. In fact, these patients may only seek treatment to alleviate circumscribed problems,like anxiety or somatic complaints. Approaches that emphasizeconcrete, interim goals, and stipulate explicit means of attaining them, thus have the best chances of success. Because individuals 
with this disorder are vulnerable to decompensation during times of stress and may experience transient episodes of psychosis,
they may also beneﬁ  t from techniques to facilitate stress reduction 
(e.g. relaxation techniques, exercise, yoga, and meditation). Fortunately, some people with schizotypal features are likely toseek treatment in times of stress.
(38) In the short-term, brief
courses of antipsychotic treatment may be useful if symptoms of psychosis appear.
Cognitive problems are also frequently amenable to concrete 
goal-oriented approaches to treatment. Patients beneﬁ  t from

goal-oriented approaches to treatment. Patients beneﬁ  t from 
understanding their cognitive strengths and weaknesses because it helps them confront and cope with long-standing difﬁ  culties 
in their lives. For example, problems in attention, verbal memory, or organizational skills contribute to failures in educational, occupational, and social endeavours, while reinforcing negative self-images and increasing performance anxiety. Knowledge of circumscribed cognitive problems allows patients to reframe their difﬁ culties in a more positive manner, and facilitate selection of 
realistic personal, educational, and occupational goals. Moreover, speciﬁ  c cognitive deﬁ  cits are often subject to partial remediation. 
For example, standard procedures will attenuate deﬁ  cits in the

For example, standard procedures will attenuate deﬁ  cits in the 
acquisition, organization, and retrieval of new information (e.g. writing information down in a ‘memory notebook’ , using appoint-ment books or planners, and rehearsing new information, among others). In some instances, the documentation of speciﬁ  c cogni-
tive deﬁ  cits (e.g. attention) can lead to academic accommodations 
in school (e.g. more time to take exams), which will help individ-uals function closer to their intellectual potentials.
At present, most early intervention programmes involve secondary prevention, which includes the early identiﬁ  cation and treatment

At present, most early intervention programmes involve secondary prevention, which includes the early identiﬁ  cation and treatment 
of clinical (usually psychotic or psychotic-like) symptoms. While intervention is necessary to alleviate clinical symptoms at any point during the disorder, it is particularly important early on because it might alter the course of the illness. Patients treated with antipsy-chotic medication during their ﬁ  rst or second hospital admission, 
for example, show better outcomes than those who are not treated until later in the course of their disorders.
Primary prevention, which involves treatment before the disorder 
manifests itself clinically, is not yet available for schizoaffective disorder, schizotypal personality disorder, or other disorders in the schizophrenia spectrum. T o develop such treatments, it will be nec-essary to predict who is most likely to develop a disorder. There

are a few encouraging approaches, including ongoing ‘high-risk’ 
studies that follow the offspring of schizophrenic parents longitu-dinally.
(39) Such studies help to identify traits early in life that 
predict which individuals are most likely to experience emergent clinical symptoms in adulthood. This type of study is particularly important because it can facilitate the formation of homogeneous high-risk groups, which in turn can facilitate the development of focused prevention strategies.With our current knowledge, it is difﬁ  cult to justify preventive 
treatments—especially medication—for people without symp-toms. The authors have argued elsewhere, however, that if people in high-risk groups (like ﬁ  rst-degree biological relatives of patients 
with schizophrenia) show clinically meaningful symptoms that can be organized into valid liability syndromes, then intervention attempts may become appropriate.
(26) The authors proposed this

(26) The authors proposed this 
course of action for people with ‘schizotaxia’ , and suggested preliminary research guidelines.
(40)
Eventually, prevention will be a primary therapeutic approach 
for the treatment of disorders in the schizophrenia spectrum. While primary prevention has yet to occur, the authors are optimistic that high-risk studies, progress in secondary prevention, and progress in discovering the genetic aetiology of the schizophrenia spectrum, will facilitate primary prevention strategies eventually.
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4.3.10 Acute and transient 
psychotic disorders
Historic introduction
Acute and transient psychotic episodes have been described since 
the end of the nineteenth century. Descriptions have varied from one country to another, so that the exact nosology has not yet been established. The links between acute psychoses (generally deﬁ  ned 
as having brief obvious psychotic symptomatology) and chronic psychoses (schizophrenic psychoses and psychoses with persistent delusions) are still under discussion.
For instance, Sections F20 and F21 in ICD-10
(1) are devoted to

(1) are devoted to 
‘Schizophrenia, schizotypal and delusional disorders’ . A speciﬁ  c 
diagnostic category named ‘Acute and transient psychotic disor-ders’ is included, distinct from Schizophrenia (F20), Schizotypal disorder (F21), Persistent delusional disorder (F22), Induced delu-sional disorder (also called folie à deux ) (F24), and Schizoaffective 
disorder (F25).
In this textbook, the acute and transient psychotic disorders 
(Chapter 4.3.10) appear in the section dedicated to schizophrenia,

603
which also includes schizotypal disorders and schizoaffective disor-
ders (Chapter 4.3.9). However, this section is clearly distinguished from the chapter in which the persistent delusional disorders are discussed (Chapter 4.4). These taxonomic divergences are justiﬁ  ed 
more by the history of acute psychoses than by scientiﬁ  c ﬁ ndings.
In the nineteenth century, German psychiatrists had already 
described akute primäre Verruckheit ,
(2) termed paranoia acuta  by 
Karl Westphal. In 1876 (published in 1878), Westphal used this term to describe an acute form of paranoia with an outburst of perceptual hallucinations, consisting mostly of hallucinatory voices and delusions, with clouding of consciousness. In 1890, Meynert repeated the clinical description but named the condition amentia.
(3)
Sigmund Freud chose this type of acute delusion with hallucina-tions for his psychoanalytic conception of psychosis.
(4)
In the sixth edition of his textbook, published in 1899,

(3)
(4)
In the sixth edition of his textbook, published in 1899, 
Kraepelin(5) included all the paranoias under dementia praecox, 
and in the eighth edition (1908–1915) he combined manic and melancholic periodic disorders in a single group, leaving acute psy-chosis with no place between these two diagnostic categories.
In 1911, Bleuler
(6) replaced the single disease dementia praecox 
by the concept of a group of schizophrenias of various clinical forms. He noticed that schizophrenia often began with an acute excitatory episode lasting from a few hours to a few years. He described a wide variation of outcome of acute forms of psychosis, but he separated acute schizophrenias from simple schizophrenia as he believed that acute forms do not necessarily end in deterioration.
In 1916, based on Karl Jaspers’ psychopathology, the Danish 
psychiatrist Wimmer

(7) described psychogenic psychosis as a reac-
tive psychosis arising after psychosocial trauma. Mayer-Gross,(8)
who proposed an organic aetiology for schizophrenia, described ‘oneiroid states’ consisting of acute psychotic symptomatology with no other speciﬁ  c organic features.
In 1961, Leonhard
(9) used Kleist’s concept of marginal psychosis 
(Randpsychosen ) to develop his description of ‘cycloid psychoses’ as 
endogenous psychoses separate from schizophrenic psychoses and from manic and melancholic psychoses. These cycloid psychoses tend to have a benign and periodic course.
Earlier (1933), Kasanin
(10) had described ‘acute schizoaffective 
psychoses’ , raising questions about the links between schizophrenic and affective diseases.
Langfeldt
(11) suggested that observation for 5 years was required

Langfeldt
(11) suggested that observation for 5 years was required 
to be able to distinguish schizophrenia and what he called schizo-phreniform psychosis. This long-term observation is a reminder of the Bleulerian concept of acute schizophrenias which could last for several years. Epidemiological studies have led to the presence in modern classiﬁ  cations of a group of acute schizophreniform 
psychoses under the rubric ‘Schizophreniform disorder’ (DSM-IV Section 295.40) or ‘Acute psychotic disorder schizophrenic-like’ (ICD-10 Section F23.2).
In France, the concept of bouffée délirante  led naturally to a 
speciﬁ  c class of acute psychoses. In 1895, Magnan
(12) and his dis ciple
Legrain(13) described bouffée délirante  or délire d’emblée  (immediate

Legrain(13) described bouffée délirante  or délire d’emblée  (immediate 
delusion) within the polymorphic delusions of the chronic insane. This concept is based on Morel’s theory of degeneration, commonly accepted in the nineteenth century. The question of whether there is a susceptibility or a predisposition to the occurrence of an acute psychosis remains unanswered.
(14)
In 1954, Ey(15,16) described the development of the concept of 
bouffées délirantes  and of acute psychoses with hallucinations from the time of Magnan to a symposium devoted to the clinical subdi-
vision of schizophrenic psychoses held at the First World Congress of Psychiatry in 1950, where the various ideas were discussed by Langfeldt, Karl Leonhard, and Aubrey Lewis (Table 4.3.10.1).
Clinical description: psychopathology

The heterogeneous group of acute and transient psychotic disorders are characterized by three typical features, listed below in descend-ing order of priority:
X suddenness of onset (within 2 weeks or less);
X presence of typical syndromes with polymorphic (changing and 
variable) or schizophrenic symptoms;
X presence of associated acute stress (stressful events such as 
bereavement, job loss, psychological trauma, etc.).
The onset of the disorder is manifested by an obvious change to 
an abnormal psychotic state. This is considered to be abrupt when it occurs within 48 h or less. Abrupt onset often indicates a better outcome. Full recovery occurs within 3 months and often in a shorter time (a few days or weeks). However, a small number of patients develop persistent and disabling states.Table 4.3.10.1  Historical development of the terminology of acute 
and transient psychotic disorders
Historic term Current terminology
1876 Westphal

Akute primäre Verruckheit
Paranoia acutaF23.3 Other acute predominantly 
delusional psychotic disorder
1890 Meynert Amentia
1895 Magnan and Legrain
Bouffées délirantesF23.0 Acute polymorphic psychotic 
disorder without symptoms of schizophrenia
1899 Kraepelin
Dementia praecoxF20.0 Schizophrenia
1909–1913 Kraepelin Paranoia F22.0 Persistent delusional disorder
1911 Bleuler
Acute-onset forms of schizophreniaF23.1 Acute polymorphic psychotic 
disorder with symptoms of schizophrenia
F23.2 Acute schizophrenia-like psychotic 
disorder
1916 Wimmer
Psychogenic psychosisF23.3 Other acute predominantly 
psychotic disorder
1924 Mayer-Gross
Oneroide ErlebnisformF23.3 Acute schizophrenia-like psychotic 
disorder
1933 Kasanin
Acute schizoaffective psychosesF25 Schizoaffective disorders
1939 Langfeldt
Schizophreniform statesF23.2 Acute schizophrenia-like psychotic 
disorder
1954 Ey
Bouffées délirantes et psychoses

disorder
1954 Ey
Bouffées délirantes et psychoses 
hallucinatoires aiguesF23.0 Acute polymorphic psychotic 
disorder without symptoms of 
1961 Leonhard
Cycloid psychosesF23.0 Acute polymorphic psychotic 
schizophrenia4.3.10 acute and transient psychotic disorders

SECTION 4  clinical syndromes of adult psychiatry 604
The general (G) criteria for these acute disorders in DCR-10 
(Diagnostic Criteria Research of ICD) are as follows.
G1  There is acute onset of delusions, hallucinations, incompre-
hensible or incoherent speech, or any combination of these. The time interval between the ﬁ  rst appearance of any psy-
chotic symptoms and the presentation of the fully developed disorder should not exceed 2 weeks.
G2  If transient states of perplexity, misidentiﬁ  cation, or impair-
ment of attention and concentration are present, they do not fulﬁ l the criteria for organically caused clouding of con-
sciousness as speciﬁ  ed for F05, criterion A.
G3  The disorder does not satisfy the symptomatic criteria for 
manic episode (F30), depressive episode (F32), or recurrent depressive disorder (F33).
G4  There is insufﬁ  cient evidence of recent psychoactive sub-
stance use to satisfy the criteria for intoxication (F1x.0),

stance use to satisfy the criteria for intoxication (F1x.0), 
harmful use (F1x.1), dependence (F1x.2), or withdrawal 
states (F1x.3 and F1x.4). The continued moderate and large-ly unchanged use of alcohol or drugs in the amounts or with the frequency to which the individual is accustomed does not necessarily exclude the use of F23; this must be decided by clinical judgement and the requirements of the research project in question.
G5  There must be no organic mental disorder (F00–F09) or 
serious metabolic disturbances affecting the central nervous system (this does not include childbirth). (This is the most commonly used exclusion clause.)
A ﬁ fth character should be used to specify whether the acute onset 
of the disorder is associated with acute stress (occurring 2 weeks or 
less before evidence of ﬁ  rst psychotic symptoms):
X F23.x0 without associated acute stress and
X F23.x1 with associated acute stress.

For research purposes it is recommended that change of the 
disorder from a non-psychotic to a clearly psychotic state is further speciﬁ  ed as either abrupt (onset within 48 h) or acute (onset in 
more than 48 h but less than 2 weeks).
Six categories of acute psychoses are presented in ICD-10, and 
we shall discuss them in order.
F23.0 acute polymorphic psychotic disorder without 
symptoms of schizophrenia
The diagnostic criteria are based on the classical symptoms of the 
true bouffée délirante  described by Magnan and Legrain.
(a) Suddenness of onset
Bouffée délirante  occurs over a period of a few hours or days,

Bouffée délirante  occurs over a period of a few hours or days, 
usually to young adults and often women in their 30s. The onset of the delirious episode is ‘like a thunderbolt in a serene sky’ . This aphorism from Legrain has the same meaning as the French classi-cal expression délire d’emblée  (immediate delusion).
Although premonitory symptoms, such as increasing perplexity 
and anxiety, may occur, the delusions start suddenly and are always accompanied by a break-up in the individual psychic life. If the onset is preceded by a stressful or traumatic event, such as resettle-ment or acculturation, this may take place some months previously and the outburst of the delirious episode is delayed. The ﬁ  fth code character of category F23 is used to specify whether acute stress 
is associated with the onset of the disorder (e.g. F23.00 has no associated acute stress).
(b) Polymorphic psychotic symptoms

The delusional themes are varied and include grandeur, persecu-tion, inﬂ  uence, possession, body transformation (depersonaliza-
tion), derealization, or world alteration; these themes change with time and may combine. Other symptoms are also varied, including hallucinations, illusions, interpretations, and intuitions.
(c) The emotional state
As a consequence of the delusions the patient experiences mood change and emotional turmoil (happiness, ecstasy, anxiety, irrita-bility). However, the criteria for manic episode, depressive episode, schizoaffective disorder, and schizophrenia are not satisﬁ  ed.
Consciousness ﬂ  uctuates with the delirious convictions and 
changes of emotion. There is a speciﬁ  c disorientation with respect 
to time and place—the passage of time ( temps vécu  according to 
Eugène Minkowski) and ‘temporality’ ( Sein und Zeit  according to

Eugène Minkowski) and ‘temporality’ ( Sein und Zeit  according to 
Ludwig Binswanger) are disturbed. This disorientation, described by Karl Jaspers as a ‘ﬁ  rst delirious experience’ ( Erlebnisse ), has to be 
understood as a dream-like state.
Ey
(15,16) differentiated the acute psychoses in terms of the spe-
ciﬁ c alteration in the perception of time rather than their transient 
course. According to Jacksonian ideas, the acute psychoses are the expression of a destructuring of consciousness to levels related to each acute psychosis.
(d) The duration of the delirious experience
In ICD-10, the criterion of a duration of less than a month distin-guishes other categories from schizophrenia (F20) and manic or depressive episodes (F30 and F32).
(e) Short recovery time

In most cases recovery from the acute psychotic disorder occurs within a few weeks or months. However, long-term prognosis is difﬁ  cult because of the risk of relapse into either a repeated 
episode or a more chronic disease. If resolution of the symptoms has not occurred after 3 months, the diagnosis should be changed to persistent delusional disorder (F22) or non-organic psychotic disorder (F28).
(f) Suggested criteria
Pull et al .(17) have suggested the following empirical criteria for 
bouffée délirante .
X Abrupt or acute onset, with no previous psychiatric disorder 
except other similar episodes.
X Absence of chronicity: the active stages disappear completely 
in a few weeks or months. Relapses can occur, but there is no psychiatric disorder between consecutive episodes.

X Speciﬁ  c symptoms: delusions and/or any type of hallucination, dep-
ersonalization and/or derealization with or without confusion, and affective disturbance manifesting as depression or euphoria. The symptoms change from day to day and even from hour to hour.
X There is insufﬁ  cient evidence for organic mental disorder, alco-
holism, or drug addiction. The exclusion clauses are less restric-tive in ICD-10, since a moderate, continued, and unchanged use of alcohol or drugs in habituated individuals does not exclude the diagnosis.

605
X The true acute psychotic disorder occurs without any associated 
psychosocial stress factor. When psychosocial stress factors are found, there is only a temporal link with the so-called ‘reactive’ acute psychosis.
(g) Long-term evolution
Bleuler(6) described one-third of cases of acute schizophrenic 
psychoses as single episode, one-third as recurrent episodes with repetition of the same acute and transient psychoses (either manic or depressive), and one-third following a course which developed as schizophrenia.
Between 1976 and 1989, Metzger and Weiber
(18) studied 885 cases 
of acute psychoses. Using the criteria of Pull et al .(17) they found 
group 303 cases of genuine bouffée délirante  (two-thirds female, 
one-third male, average age of 32 years). They followed the course of 191 cases (over an average period of 6.2 years): 34 per cent did not relapse, 24 per cent had recurrent and transient episodes, 34 per cent developed schizophrenia, and over 7 per cent developed

a periodic affective disorder (manic and depressive states). The 
relapse or chronic course rate was higher in the group without triggering factors ( n = 92) than in the group with triggering factors 
(n = 99). The difference between true bouffée délirante  (no trigger-
ing factors) and other acute and transient psychotic disorders raises questions about their pathogenesis.
In the ﬁ  rst 2 years, it is essential to distinguish bouffée délirante
from schizophrenia
(19) and other acute psychoses.(20) Follow-up 
during this period must be very careful.
F23.1 acute polymorphic disorder with symptoms of 
schizophrenia ( bouffée délirante  or cycloid psychosis 
with symptoms of schizophrenia)
This diagnostic category combines the symptoms of acute

This diagnostic category combines the symptoms of acute 
polymorphic psychotic disorder with some typical symptoms of schizophrenia (F20) present for most of the time. However, the schizophrenic symptoms are not precisely listed. F23.1 can be a provisional diagnosis, which is changed to schizophrenia if the criteria of F20 persist more than a month.
Acute polymorphic disorder with symptoms of schizophrenia 
satisﬁ  es the general criteria for acute and transient psychotic 
disorders:
X acute onset of less than 2 weeks
X polymorphic delusions and hallucinations or perceptual distur-
bances leading to incomprehensible or incoherent speech
X clouding of consciousness with impairment of attention or 
concentration, disorientation, perplexity, etc.
X emotional turmoil and affective symptoms (depressed mood,

X emotional turmoil and affective symptoms (depressed mood, 
euphoria, anxiety, irritability) without the symptomatic criteria for manic–depressive or recurrent depressive disorders
X rapid changes of the type and intensity of symptoms
X no evidence of causation by organic or psychoactive substances.
It is also associated with some schizophrenic symptoms which 
are present most of the time:
X mental automatism (thought echo, insertion, withdrawal, or 
broadcasting)
X control, influence, passivity referred to body movements, 
thoughts, actions, or sensationsX hallucinations with commentary
X catatonic behaviour
X negative symptoms.
The ICD-10 clinical criteria give no information about psychotic 
or schizophrenic symptoms or about the action of antipsychotic drugs on these symptoms.
Leonhard
(9) described cycloid psychosis as an episode with

Leonhard
(9) described cycloid psychosis as an episode with 
clouding of consciousness and a marked alteration of thinking. Many authors have reported follow-up studies of cycloid psychoses,
(21–23) which conﬁ  rm the better prognosis of cycloid 
psychoses than of schizophrenias and schizoaffective disorders.
F23.2 acute schizophrenia-like psychotic disorder 
(schizophreniform psychosis)
This acute psychotic disorder lasts for less than a month and is 
mostly schizophrenic. The polymorphic psychotic symptoms are stable (no rapid changes, no emotional turmoil or confusion), sometimes with emotional instability.
The duration criterion is the most important. This category is a 
provisional diagnosis and appears to include such disparate descriptions as oneirophrenia (oneiroid states or Erlebnisform
(8)), 
schizophrenic reaction (DSM.IV 298.8, Brief reactive psychoses), and schizophreniform psychosis.

(8)), 
(11) In ICD-10, if the ﬁ  rst episode 
lasts for more than a month, it has to be considered as an acute onset of schizophrenia.
The Scandinavian psychiatric school
(24) justify the retention of 
this category because of the very good and rapid recovery, and have tried to determine factors in the personal and family history pre-dicting the onset of schizophrenia.
Schizophreniform disorder remains in DSM-IV (295.40) because 
the evidence linking it to typical schizophrenia remains unclear, but the duration criterion is less restrictive (up to 6 months). Features suggesting a good prognosis are onset within 4 weeks, confusion at the height of the psychotic episode, previously good social and occupational functioning, and absence of blunted or ﬂ  at 
affect.
F23.3 other acute predominantly delusional 
The main clinical features of this category are delusions and

affect.
The main clinical features of this category are delusions and 
hallucinations. The foreground delusions are mostly persecutory (delusions that the person or close relatives are being malevolently treated or are under external inﬂ  uence, with thought disturbances); 
auditory hallucinations are present in the background. Despite their stability, these psychotic features do not meet the criteria for schizophrenia (F20).
As for F23.0, the duration of this acute predominantly delusional 
psychotic episode must be less than 3 months. If the persecutory delusions persist for more than 3 months, the diagnosis changes to persistent delusional disorders (F22). This development from F23.3 to F22 is reminiscent of the classical paranoia acuta . Thus, 
both paranoid reaction and psychogenic paranoid psychosis are included in F23.3. Paranoid reaction must be distinguished from

both paranoid reaction and psychogenic paranoid psychosis are included in F23.3. Paranoid reaction must be distinguished from 
induced delusional disorder or folie à deux  (F24), in which the 
delusions of the ‘dominated’ patient disappear when the two people are separated (see Chapter 4.4).
If the background auditory hallucinations persist for more than 
3 months, the diagnosis is changed to other non-organic psychotic 4.3.10 acute and transient psychotic disorders

SECTION 4  clinical syndromes of adult psychiatry 606
disorders (F28). This diagnostic category is deﬁ  ned by exclusion: 
the persistent hallucinatory disorder does not meet the criteria for schizophrenia (F20), persistent delusional disorders (F22), acute and transient psychotic disorders (F23), psychotic types of manic episode (F30.2), or severe depressive episode (F32.3). F28 also corresponds to chronic hallucinatory psychosis, as explicitly noted in ICD-10.
F23.8 other acute and transient psychotic disorders
This category includes any other acute and transient psychotic disorders with no evidence of organic cause that are not classiﬁ  able 
under previous F23 categories, such as ephemeral delusions or hallucinations and undifferentiated excitement.
F23.9 acute and transient psychotic disorder 
unspeciﬁ  ed
Brief psychotic disorder (298.8) is deﬁ  ned in DSM-IV as an episode

Brief psychotic disorder (298.8) is deﬁ  ned in DSM-IV as an episode 
of acute and transient psychotic disorders (delusions and halluci-nations with disorganized speech and behaviour) which lasts at least a day but less than a month with eventual full return to previ-ous level of functioning. If the symptoms occur after stressful events in the person’s life, brief psychotic disorder with marked stressor(s) has to be speciﬁ  ed. If the symptoms occur within 
4 weeks post-partum, brief psychotic disorder with post-partum onset has to be speciﬁ  ed.
Cultural variants
Other forms of acute psychoses have been observed in both 
traditional and developing countries, with high prevalence in Asia, Africa, and Latin America. These brief psychotic episodes are culture-bound syndromes, often with immediate precipitating stress or life events.
(25) There is disorganized behaviour, delusions,

(25) There is disorganized behaviour, delusions, 
thought disorders, confusion, and mood disorders, usually with full recovery and no relapse in a 1-year follow-up.
The culture-speciﬁ  c disorders
(26) and their potentially related 
syndromes are often acute and transient. The status of these culture-reactive disorders is controversial and needs more clinical and epidemiological research. The mode of assignment to catego-ries in ICD-10 does not suggest category F23.
Appendix I of DSM-IV (Outline for cultural formulation and 
glossary of culture-bound syndromes) lists 25 syndromes, with a glossary mostly using the local terms (seven in Hispanic languages, ﬁ ve in English, and one in French). Bouffée délirante , described only 
in West Africa and Haiti, is deﬁ  ned as episodes resembling brief 
psychotic disorder and classiﬁ  ed in F23.0. Messich and Lin
(25) have

(25) have 
suggested that the whole group of culture-bound syndromes should be classiﬁ  ed as acute and transient psychotic disorders, 
although this is justiﬁ  ed only for a very few such as amok  (dissocia-
tive episode with persecutory ideas and aggressive behaviour from Malaysia), shin-byung  (Korean dissociation and possession), and 
spell (trance state in southern United States).
ICD-10 includes the two Malaysian syndromes koro and latah  as 
well as dhat  (India) in F48.8, Other speciﬁ  ed neurotic disorders.
International follow-up studies have shown that cultural factors

International follow-up studies have shown that cultural factors 
can influence the course and prognosis of acute psychoticdisorders. In 1979, the World Health Organization compared the course of schizophrenia (295), psychotic depression, mania, and other psychoses in different cultures, using the ICD-9 criteria for the diagnoses. The outcome for the schizophrenic group was better 
in emerging countries than in the industrialized world. These results probably explain the individualization of category F23 in ICD-10.
Some authors
(27) have suggested that short-lived psychotic 
episodes are expressions of overcharged mechanisms of defence, or of individual psychological fragility. The brief psychosis is an understandable development of the psychic life of the subject and has a cathartic effect.
Culturally related syndromes are discussed further in

Culturally related syndromes are discussed further in 
Chapter 4.16.
Treatment
Short-term treatment
Acute psychotic syndromes require early hospitalization in either an inpatient psychiatric unit or a crisis centre. These syndromes are to be considered as psychiatric emergencies. The decision to admit to hospital is taken in order to make a careful physical and mental examination clinical evaluation, to separate the patient from his or her environment, to provide a reassuring setting, and to prevent any suicidal or aggressive tendencies.
(28)
The goals are to prevent auto or heteroagressivity (suicidal 
potential, affective symptoms, agitation, aggressive behaviour,command hallucinations, etc.), to reduce the acute psychotic symptoms, to suppress the causal factors and to establish anearly therapeutic alliance with the patient and his family. Antipsychotic drugs medications are prescribed.
(29) Some clini-

cians wait for a day or two before starting neuroleptic therapyin order to eliminate an organic cause (a general medical condition or substance abuse disorder can be present with acute and transient psychoticsymptoms) and prescribe benzodiazepines rather than neuroleptics. More often, however, antipsychotic treatmentstarts immediately after physical, electrophysical, radiological assessments, and laboratory tests (CBC, blood electrolytes,cholesterol, triglycerides, toxicology screen, etc.) to evaluatehealth status.
The choice of antipsychotic medication depends on the 
clinician’s experience and the clinical features. Second-generation antipsychotic medications (amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone) are commonly prescribed 
as ﬁ rst-line treatment; clozapine is reserved to schizophrenia with

as ﬁ rst-line treatment; clozapine is reserved to schizophrenia with 
high suicidal potential or to resistant schizophrenia. First-generation antipsychotic medications (chlorpromazine, haloperidol, etc.) are second choice or adjunctive medications.
In cases of major anxiety or agitated behaviour, short-acting 
sedative drugs neuroleptics such as ﬁ  rst-generation antipsychotics 
chlorpromazine (100–500 mg/day), (loxapine: 50–300 mg/day), with or without benzodiazepines (lorazepam) can be prescribed or levomepromazine (25–300 mg/day) are chosen, or zuclopenthixol acetate (100–300 mg every 3 days by intramuscular injection) is used as a short-acting depot antipsychotic. Parenteral administra-tion (standard intramuscular administration) may be required if the patient refuses oral medication, or if a rapid effect is required because the patient is seriously uncooperative or is too dangerously disturbed.
Predominance of delusions and hallucinations indicates a

Predominance of delusions and hallucinations indicates a 
high-potency antipsychotic agent as haloperidol (5–15 mg/day) or ﬂ upenthixol (80–200 mg/day).

607
Benzodiazepines may be given to potentiate the action of the 
neuroleptics. Alprazolam (0.5–4 mg/day), clorazepate (50–200 mg/day), and lorazepam (2–5 mg/day) produce rapid sedation in acutely psychotic patients if they are used with a neuroleptic. Some clinicians prefer the combination of two neuroleptics (haloperidol–levomepromazine, haloperidol–cyamemazine).
New compounds with fewer adverse effects can be used (amisul-
pride, 800–1200 mg/day; olanzapine, 5–20 mg/day; quetiapine, 75–500 mg/day; risperidone, 2–10 mg/day).
In culture-bound syndromes the prescription of antidepressants 
is often recommended as primary treatment.
The dosage may be adjusted from low doses and gradually 
increased, or adjusted to the standard dose after a ﬁ  rst loading dose.

increased, or adjusted to the standard dose after a ﬁ  rst loading dose. 
Frequent monitoring to assess drug response and adverse effects (extrapyramidal side-effects, orthostatic hypotension, anticholin-ergic effects, and temperature dysregulation) is essential, and corrections and prophylactic prescriptions (e.g. antiparkinsonian medications) may be necessary.
Sociotherapy (occupational or intensive) and psychotherapy 
(reality–adaptive–supportive) are indicated depending on the state of the patient and his environment, with individual, family, or rehabilitation care.
Continuation treatment
The effectiveness of psychopharmacotherapy is usually manifested in the ﬁ  rst 6 weeks, with improved sleep, regression of agitation, 
recovery from anxiety and delusion, and ﬁ  nally disappearance of

recovery from anxiety and delusion, and ﬁ  nally disappearance of 
the psychotic features. When there is no recovery or improvement either another antipsychotic drug should be used or the dosage of the ﬁ  rst increased. Worsening of the symptoms, serious side-effects, 
or a poor response to pharmacotherapy may lead to the main indications for electroconvulsive therapy.
If mood disorders or cyclic episodes occur, treatment with 
antidepressants, mood stabilizers (lithium or valproate), or an anti-convulsant drug (carbamazepine) may be indicated. Care must be taken to distinguish between a post-neuroleptic depression and the development of a (schizo)affective disorder.
Prevention of recurrence
The possibility that psychotic symptoms may re-emerge has to be borne in mind during the ﬁ  rst 2 years of follow-up. Low-dosage

The possibility that psychotic symptoms may re-emerge has to be borne in mind during the ﬁ  rst 2 years of follow-up. Low-dosage 
pharmacotherapy must be maintained for 1 or 2 years after recovery. During this long-term follow-up, periodic assessment and effective clinical care with social and psychological therapy are essential.
Patients are often hospitalized under constraint because they do not acknowledge the disorder. The initial non-compliance leads to the frequent use of ﬁ  rst-generation antipsychotic medications 
classic intramuscular neuroleptics. After remission recovery, a switch to a second-generation antipsychotic medication newer antipsychotic drug, which is better tolerated, helps to ensure the acceptance of long-term treatment when the psychotic symptoms have disappeared.
In general, psychotherapy and psychosocial care are more effec-

tive in an outpatient setting after symptomatic remission recovery has started. A good relationship between patient and psychiatrist together with collaboration with the family practitioner and social workers improve the long-term prognosis. If resources allow, psy-
chotherapy by a trained practitioner, behavioural therapy, or family therapy may be combined with a low-dose pharmacotherapy.
(30)
There are no substantial sources of information in the English language. 
The following will be of use to those who read French or Spanish. Others should seek further information using an information retrieval system such as Medline.
Weibel, H. and Metzger, J.Y. (2007). Psychoses délirantes aiguës.
Encyclopédie Médico—chirurgicale. Psychiatrie , 37–230 A 1O 15
p. 142 ref.
Segarra, E.R., Eguiliz, U.I., and Gutierrez, F. (2007). Trastorno 
esquizofreniforme y trastorno esquizoafectivo. 158 ref. in Trastornos

p. 142 ref.
esquizofreniforme y trastorno esquizoafectivo. 158 ref. in Trastornos 
psicoticos  (457–592 ) Coordinador M. Roca Benassar. Fundacion 
española de Psiquiatria y Salud mental. Barcelona: Ars medica.
 1. World Health Organization. (1992). International statistical 
classiﬁ  cation of diseases and related health problems,  10th revision. 
 2. Bercherie, P . (1980). L’école d’Illenau. In Les fondements de la clinique
(ed. Le Seuil), pp. 119–28. Ornicar, Paris.
 3. Meynert, T. (1890). Klinische vorlesungen über psychiatrie auf 
wissenschaftlichen grundlagen . Braumüller, Vienna.
 4. Freud, S. (1917). Metapsychologie Ergänzung Zurtraumlehre. 
In Gesammelte werke . Internationales Psychoanalytischer Verlag, 
Leipzig, 1947.
 5. Kraepelin, E. (1899). Psychiatrie  (6th edn). Barth, Leipzig.
 6. Bleuler, E. (1911). Dementia praecox oder Gruppe der Schizophrenien.

 6. Bleuler, E. (1911). Dementia praecox oder Gruppe der Schizophrenien. 
In Aschaffenburg Handbuch des Psychiatrie . Deuticke, Leipzig.
 7. Wimmer, A. (1916). Psykogene sindssygdomsformer. In St. Hans 
Hospital, Jubilee Publication. Gad, Copenhagen.
 8. Mayer-Gross, W. (1924). Selbschilderungen der Verwirrtheit 
(Die oneroïde Erlebnisform). Stringler, Berlin.
 9. Leonhard, K. (1961). Cycloid psychoses: endogenous psychoses which 
are either schizophrenic or manic-depressive. Journal of Nervous and 
Mental Diseases ,107, 633–48.
10. Kasanin, J. (1933). The acute schizo-affective psychoses. American 
Journal of Psychiatry ,13, 97–126.
11. Langfeldt, G. (1939). The schizophreniform states . Oxford University 
Press, London.
12. Magnan, V . (1893). Leçons cliniques sur les maladies mentales .
Bataille, Paris.
13. Legrain, M. (1895). Du délire des dégénérés . Progrés Medical, Paris.

14. Samuel-Lajeunesse, B. and Heim, A. (1994). Psychoses délirantes 
aigues. In Encyclopedie de medecin et de chirurgie , 37 230, A10. 
Editions T echniques, Paris.
15. Ey, H. (1954). Bouffées délirantes et psychoses hallucinatoires aigues. 
In Etudes psychiatriques , Vol. III. Desclée de Brower, Paris.
16. Ey, H. (1955). Psychoses délirantes aigues (bouffées délirantes aigues, 
psychoses hallucinatoires aigues, états oniroïdes). In Encyclopedie
de medecin et de chirurgie , 37 230, A10, pp. 1–6. Editions 
T echniques, Paris.
17. Pull, C.B., Pull, M.C., and Pichot, P . (1987). Des critères empiriques 
français pour les psychoses. II-Consensus des psychiatres français et déﬁ nitions provisoires. Encéphale ,13, 53–7.
18. Metzger, J.-Y. and Weibel, H. (1991). Les bouffées délirantes. Congrès de

18. Metzger, J.-Y. and Weibel, H. (1991). Les bouffées délirantes. Congrès de 
psychiatrie et de neurologie de langue française . Masson, Paris.
19. World Health Organization. (1979). Schizophrenia: an international 
20. Guilloux, J. (1987). Psychoses délirantes aigues. Statut nosologique et 
evolution. Revue Française de Psychiatrie ,5, 9–13.4.3.10 acute and transient psychotic disorders

SECTION 4  clinical syndromes of adult psychiatry 608
21. Perris, L. (1974). A study of cycloid psychoses. Acta Psychiatrica 
Scandinavica ,253(Suppl.), 1–75.
22. Brockington, I.F., Perris, L., Kendell, R.E., et al. (1982). The course and 
outcome of cycloid psychoses. Psychiatry in Medicine ,12, 97–105.
23. Barcia, D. (1998). Psicosis cicloides (psicosis marginales, bouffées 
délirantes) . Triacastela, Madrid.
24. Strömgren, E. (1963). Schizophreniform psychosis. Acta Psychiatrica 
Scandinavica ,41, 483–9.
25. Messich, J. and Lin, K.M. (1995). Acute and transient psychotic 
disorders and culture-bound syndromes. In Comprehensive textbook 
of psychiatry  (eds. H. Kaplan and B. Sadock) (6th edn), Vol. 1, 
pp. 1049–57. Williams and Wilkins, Baltimore, MD.
26. World Health Organization. (1993). The ICD-10 classiﬁ  cation of mental 
and behavioural disorders-diagnostic criteria for research, Annex 2 .

World Health Organization, Geneva.27. Cousin, F.R. and Vanelle, J.M. (1987). Défense et illustration du concept 
de bouffée délirante aiguë. Information Psychiatrique ,63, 315–21.
28. American Psychiatric Association (2004). Practice guideline for the 
treatment of patients with schizophrenia. Supplement to the American 
Journal of Psychiatry ,161.
29. Janicak, P ., Davis, J., Preskorn, S., et al. (1997). Management of 
acute psychosis. In Principles and practice of psychopharmacotherapy
(eds. P .G. Janicak, J.M. Davis, S.H. Preskorn, and F.J. Ayd) (2nd edn), pp. 110–39. Williams and Wilkins, Baltimore, MD.
30. Rochet, T., Daléry, J., and De Villard, R. (1995). Troubles psychotiques 
aigus et transitoires. In Thérapeutique psychiatrique  (eds. J.L. Senon,

aigus et transitoires. In Thérapeutique psychiatrique  (eds. J.L. Senon, 
D. Sechter, and D. Richard), pp. 797–803. Hermann, Paris.

4.4
Persistent delusional 
symptoms and disorders
Delusional disorder (DSM-IV 297.1 and ICD-10 F22)(1,2) is a 
psychotic illness with some superﬁ  cial resemblances to schizophre-
nia from which, however, it is quite distinct. It presents with a stable and well-defined delusional system, which is typically ‘encapsulated’ within a personality, which retains many normal aspects, unlike the situation in schizophrenia in which there is widespread personality disorganization in addition to the psychotic features. Nevertheless, although many normal aspects of the personality are preserved, the individual’s way of life becomes progressively distorted by the intensity and intrusiveness of the delusional beliefs. Hallucinations may be present but are not usually prominent. This is a chronic disorder, probably lifelong in most instances, which retains an unjustiﬁ  ed reputation for being

untreatable. Because of the nature of their delusions, many patients are unwilling to accept that they have a mental disorder or that they require psychiatric treatment but, if they can be persuaded to coop-erate and accept appropriate medication, the condition can be shown to respond to treatment in a remarkably high proportion 
of cases.
Delusional disorder used to be known as ‘paranoia’ , and the terms 
are virtually synonymous. Paranoia and its related disorders were regarded as an important group of psychiatric illnesses until the early part of the twentieth century. Then, because of changing diagnostic and classiﬁ  catory approaches, especially a tendency to 
overdiagnose schizophrenia, the diagnosis of paranoia all but disappeared from standard classiﬁ  catory systems. In 1987, paranoia 
was again ofﬁ  cially recognized by DSM-IIIR but was renamed 
delusional (paranoid) disorder—since simpliﬁ  ed to delusional

delusional (paranoid) disorder—since simpliﬁ  ed to delusional 
disorder. It is the only ofﬁ  cially acknowledged member of the old 
group of paranoid illnesses appearing in DSM-IV and ICD-10.
Although the diagnosis of paranoia all but ceased for many years, 
the illness and its sufferers did not disappear. When the phenome-na of the disorder came to attention the patient was either labelled as schizophrenic or else a speciﬁ  c feature of the delusional phenom-
enology was seized upon and spurious diagnoses were described. Thus we have a multiplicity of apparently disparate diagnoses such as de Clérambault’s syndrome (delusional erotomania), the Othello syndrome (delusional jealousy), querulant paranoia (a form of persecutory delusional disorder), monosymptomatic hypochondriacal psychosis (delusional disorder with somatic preoccupations), and many others. The result has been an extraor-

dinarily scattered literature with cases recorded in a variety of med-
ical and non-medical sources, but very few in psychiatric journals 
until recently. Since DSM-IIIR there has been a serious attempt to resolve the confusion and to diagnose paranoia/delusional disorder by its own intrinsic features, but many problems still bedevil the nomenclature.
Jaspers, in discussing paranoia, said: ‘Why are the paranoics 
as deﬁ  ned by Kraepelin so rare, yet when they do occur they are 
so typical?’ This remains true because there are striking similarities from case to case and the illness’ features clearly distinguish it from other psychoses, yet many psychiatrists continue to label it erroneously.
DSM-IV and ICD-10 provide criteria to differentiate delusional 
disorder as an illness sui generis  and these are now widely accepted. 
This section adopts that ofﬁ  cial approach but with two caveats. The 
ﬁ rst is that the descriptions are bald and not very helpful to

ﬁ rst is that the descriptions are bald and not very helpful to 
the clinician who has not actually seen cases of the disorder. The second is that the category of delusional disorder (persistent delu-sional disorders in ICD-10) may well be overrestrictive as it stands. However, some well-respected authorities take a somewhat differ-ent approach, regarding ‘delusional disorders’ as all psychiatric illnesses with delusions and then subcategorizing according to the underlying syndrome, which might be severe mood disorder, schizophrenia, actual delusional disorder, etc. Therefore the reader of any text must be aware of a particular author’s criteria for diag-nosis in this area.
Emil Kraepelin (1856–1926) clearly described paranoia and 
included it in a continuum of illnesses with delusional features, 
especially paraphrenia and paranoid schizophrenia. This so-called

especially paraphrenia and paranoid schizophrenia. This so-called 
‘paranoid spectrum’ will be brieﬂ  y alluded to later. Paranoid schizo-
phrenia continues to be a widely used diagnosis but usually in the 
context of schizophrenia. Paraphrenia is not ofﬁ  cially acknowl-
edged in DSM-IV or ICD-10 but cases ﬁ  tting its traditional descrip-
tion are quite commonly seen in practice. The present author regards it as a signiﬁ  cant entity and the reader is encouraged to 
become familiar with descriptions to be found elsewhere.
At present, ‘delusional disorder’ is both an illness category and 
essentially the only syndrome contained within that category. In recent years, another diagnosis—delusional misidentiﬁ  cation 
syndrome ( DMIS )—has come into increasing prominence. 
Originally described in 1923 by Capgras and Reboul-Lachaux
(3) as

SECTION 4  clinical syndromes of adult psychiatry 610
an illness in which the individual is delusionally convinced that 
someone familiar in the environment has been replaced by an almost exact double, this ‘Capgras syndrome’ led a rather marginal existence in the literature for many years. Lately, however, there have been considerably more case-reports of better quality and clinical subtypes have been established. Most importantly, 
sound psychological and neuropathological work has increasingly shown signiﬁ  cant cerebral pathologies in a high proportion of 
sufferers.
DMIS is not currently recognized by DSM or ICD but in many 
respects it resembles delusional disorder and should certainly be included in an expanded category of that disorder.
Finally, there is an important phenomenon which is found in

Finally, there is an important phenomenon which is found in 
association with all illnesses with delusions, especially delusional disorder. This is named ‘shared psychotic disorder’ in DSM-IV and ‘induced delusional disorder’ in ICD-10, but is often still referred to by its long-established name folie à deux . Here, the primary 
patient has a bona ﬁ  de delusional illness and a secondary patient 
has come to accept the delusional beliefs as true. The secondary patient is usually a highly impressionable individual living in pro-longed close contact with the other; he or she is not truly deluded, but retains the beliefs tenaciously as long as the intimate relation-ship is maintained. A less common variety is when two people each have genuine delusional disorders and, through close proximity, come to share identical abnormal beliefs. Folie à deux  is not uncom-

mon and, as will be explained later, there are very practical reasons why the clinician should be aware of its possible presence and the ways in which it may inﬂ  uence management of the case.
The paranoid spectrum(4)
Since Kraepelin’s time there has been a tacit acceptance by many 
psychiatrists of a spectrum simpliﬁ  ed as:
delusional disorder—paraphrenia—paranoid schizophrenia.
Somewhat anecdotally, the literature suggests that approximately 
10 per cent of cases of delusional disorder or paraphrenia will deteriorate to schizophrenia though, in general, most cases of delusional disorder remain diagnostically stable in the long term. Several reports have indicated that, as one moves to the delusional disorder end, a family history of schizophrenia becomes progres-sively less common. The risk for schizophrenia in the close family 
of a case of delusional disorder appears to be much the same as

of a case of delusional disorder appears to be much the same as 
in the general public. In paranoid schizophrenia the family history of schizophrenia is approximately half as common as in other schizophrenias and profound disintegration of personality is less frequent.
When dealing with cases in this general area the clinician should 
bear in mind the concept of a paranoid spectrum. This, plus knowledge of constituent illnesses, will make it easier to distinguish delusional disorder from superﬁ  cially similar conditions, a matter 
of considerable importance when considering treatment and prognosis.
Problems of nomenclature

Although English-speaking psychiatrists (and most members of the public) use the word ‘paranoid’ to mean ‘persecutory’ , strictly speaking it just means ‘delusional’ . In many writings on ‘paranoia’ and ‘paranoid’ disorders, authors do not make it clear whether delusions are present or not in their cases.Unfortunately, with the passage of time, the term ‘paranoid’ has 
come to be used so loosely that it has lost any meaningful clinical connotation. Paranoia should now be regarded as an historical usage, pretty well synonymous with delusional disorder.
The word ‘paranoid’ is still used in the ofﬁ  cial diagnoses of para-

noid schizophrenia and paranoid personality disorder. The former is acceptable because the illness has delusions as a prominent fea-ture, but it is quite illogical in describing a personality disorder, which cannot have delusions. Since it is unlikely that the personal-ity disorder will be renamed soon, the reader should be aware of such pitfalls in our psychiatric terminology and consequently the need for ultra-careful case-descriptions.
Although the form  of delusional disorder is remarkably charac-
teristic, the delusional contents  and the ways in which cases come 
to attention are extremely varied, and this has led to an extraordi-
narily complex history. The core description, that of paranoia, 
gradually crystallized in the latter half of the nineteenth century and was deﬁ  nitively delineated by Kraepelin, who recognized

gradually crystallized in the latter half of the nineteenth century and was deﬁ  nitively delineated by Kraepelin, who recognized 
subtypes with delusional contents of grandiosity, persecution, erotomania, and jealousy, and also allowed for the possibility of a hypochondriacal content. He clearly differentiated paranoia from dementia praecox  (i.e. schizophrenia). Kraepelin later doubted 
whether hallucinations could be present: in fact, non-prominent hallucinations are now acceptable and in every other respect Kraepelin’s century-old deﬁ  nition of paranoia still largely serves to 
describe present-day delusional disorder.
(5)
Subsequently, Kraepelin(5) introduced the concept of paraphre-
nia, an illness similar to paranoid schizophrenia but with signiﬁ  -

(5)
cantly better preservation of affect and of personality. As already mentioned, he regarded paranoia, paraphrenia, and paranoid schizophrenia as a relatively discrete group of illnesses, later referred 
to as the paranoid spectrum.
It was later found that a minority of cases of paranoia and 
paraphrenia eventually deteriorated to schizophrenia and this somewhat illogically led to these diagnoses being progressively ignored. Despite this, speculation on the nature of delusions continued, most notably by Jaspers (1883–1969),
(6) Kretschmer 
(1888–1964),(7) and Freud (1856–1939) and his followers. These

(1888–1964),(7) and Freud (1856–1939) and his followers. These 
speculations contributed a good deal to the descriptive phenome-nology of delusions but whereas we know a good deal about delu-sional contents, we understand little about the origin of delusions or of delusional illnesses, or the reasons for their unique features.
(8)
Unfortunately, as much of the writing on delusions appeared when most psychoses, and certainly paranoia, had no effective treat-ments, writers usually dwelt on the untreatability of paranoia, a pessimistic view that persists but is no longer warranted.
From the 1970s onwards, interest in paranoia reappeared and 
a more optimistic view of treatment emerged. Since its renaissance as delusional disorder in DSM-IIIR in 1987, paranoia has again become a respectable diagnosis. Not only that, it has subsumed several quasi-disorders which were undoubtedly delusional but 
which had been described superﬁ  cially on the strength of their

which had been described superﬁ  cially on the strength of their 
delusional content alone. Several of these have already been noted (see p. 281).
Nowadays the clinical description of delusional disorder is well 
established, but adequate case series are rare and scientiﬁ  c investi-
gations are in their infancy, except in the case of the diagnosis 
which still remains ofﬁ  cially unrecognized, delusional misidentiﬁ  -
cation syndrome, in which underlying brain abnormalities are

611
commonly demonstrable. The separateness of delusional disorder 
from schizophrenia is beyond doubt, but its relationship to the other constituents of the paranoid spectrum still has to be deter-mined. Delusional disorder is no longer regarded as rare, but many years of neglect have left many psychiatrists sadly unaware of its characteristic features.
Delusions: clinical aspects
A delusion may be deﬁ  ned very loosely as a mistaken idea which 
is held unshakably by the patient and which cannot be corrected. As will be seen, this is not a satisfactory deﬁ  nition, although it may 
be a useful starting point for clinical recognition of a delusional process. This brief exposition is concerned to facilitate clinical recognition and not to dwell on psychopathological theories, which are dealt with in detail elsewhere in this book.
It is a widely held opinion that delusions are qualitatively differ-

ent from normal ideas or beliefs and have an all-or-nothing aspect. The DSM-IV deﬁ  nition initially seems to accept this viewpoint, 
stating that a delusion is ‘A false belief based on an incorrect inference about external reality that is ﬁ  rmly sustained despite what 
almost everyone else believes and despite what constitutesincontrovertible and obvious proof or evidence to the contrary. The belief is not one ordinarily accepted by other members ofthe person’s culture or subculture’ . But the deﬁ  nition goes on to say 
that it is often difﬁ  cult to distinguish between a delusion and
an overvalued idea (in which there is an unreasonable belief oridea but not held with such pathological certitude as in a delusion), and that ‘Delusional conviction occurs on a continuum’ fromnormal to abnormal. These two statements markedly lessen theinitial description of the absolute nature of the delusionalwrongness.

The deﬁ  nition of delusion by Mullen
(9) based on the earlier 
description by Jaspers is widely quoted and its implications are largely accepted by DSM-IV and ICD-10. He characterizes delu-sions as follows:
1 They are held with absolute conviction.2 The individual experiences the delusional belief as self-evident 
and regards it as of great personal signiﬁ  cance.
3 The delusion cannot be changed by an appeal to reason or by 
contrary experience.
4 The content of delusions is unlikely and often fantastic.
5 The false belief is not shared by others from a similar socio-
economic group.
Clinicians widely employ the terminology on delusions intro-
duced by Jaspers, for example when they use terms such as‘primary’ and ‘secondary’ delusions, ‘delusional mood’ (Wahnstimmung ), and ‘delusional memory’ . These concepts are of

duced by Jaspers, for example when they use terms such as‘primary’ and ‘secondary’ delusions, ‘delusional mood’ (Wahnstimmung ), and ‘delusional memory’ . These concepts are of 
some descriptive and possibly heuristic value, but they do not prove particularly helpful in distinguishing delusions fromovervalued ideas in individual cases, nor in deciding whether a particular delusional phenomenon is speciﬁ  c to a given mental 
disorder.
In a sense, all delusions are secondary in that they are the 
product of a pathological process in the brain which, in most cases, we can only guess at. It is sometimes useful to differentiate clinically between the ‘primary’ or ‘autochthonous’ delusion, which appears fully ﬂ  edged and relatively suddenly, and the
‘secondary’ delusion, which is a further development within the

‘secondary’ delusion, which is a further development within the 
delusional system and may sometimes seem to be the individu-al’s way of rationalizing his delusional beliefs although, of course, the rationalization must necessarily be ﬁ  ltered through a 
mind already thought-disordered and affected by delusions.For example, the initial belief may be that the police are watch-ing him night and day; the secondary delusion ‘explains’ that this is because he has secret information about aliens which the authorities do not wish divulged. The better organized thedelusions, the more convincing are the ‘explanations’ , even to outsiders.
Not all primary delusions arise suddenly and, in fact, it must be

Not all primary delusions arise suddenly and, in fact, it must be 
presumed that in most cases the suddenness is more apparent than real. Almost certainly, unless the delusion is the result of an acute brain dysfunction such as may follow a head injury or delirium, there is a lead-up process, which may be accompanied by the afore-mentioned Wahnstimmung , a mood state compounded of anxiety, 
perplexity, and a sense of impending crisis. When the delusion crystallizes, the delusional mood often disperses and is replaced by a sense of revelation and of certainty. It seems likely that this phenomenon occurs in a proportion of delusional disorder patients and it often happens that, at the moment of revelation, some coincidental but irrelevant circumstance is picked upon to explain the appearance of the new belief. For example, a media event, a thunderstorm, a chance telephone call, etc., may thereafter be, in the patient’s mind, the ‘cause’ .

While we regard delusions as one of the most characteristic 
elements of all the psychotic illnesses and a sine qua non in the 
diagnosis of delusional disorder, clear-cut description, and deli-neation have proved elusive despite many years of study and experiment.
(10) In fact, it would seem that none of the characteris-
tics of delusion which we traditionally accept stand up completely to scientiﬁ  c scrutiny. In particular, nowadays the so-called bizarre-
ness of a delusion has been shown to have little or no distinguish-ing value.
(11)
Much of the classical work on delusions was done in pretreat-
ment times when the chronic condition was readily available for study in institutions. In the present era our aim is to diagnose psychotic disorders as early as possible, sometimes even before frank delusions are evident, and to begin treatment at once. Neuroleptics rapidly interfere with many psychopathological 
processes; they certainly suppress delusions, although not necessarily

processes; they certainly suppress delusions, although not necessarily 
permanently. Of course this makes ongoing experimental observa-tions of delusions, especially of the acute variety, all but impossible in clinical circumstances. Psychiatrists ﬁ  nd themselves in the para-
doxical situation of diagnosing illness because of the presence of delusions whose scientific validity is largely unsubstantiated, and then causing these to disappear before they can be veriﬁ  ed 
properly. Nevertheless, until we have more objective means of making diagnoses it remains essential that, as far as we can, we 
recognize delusions when they occur and separate them from other 
abnormal psychopathological appearances.
How can a clinician deal with this? Firstly it seems inescapable 
that he or she be both experienced and insightful. Given these 
qualities, it often does seem possible to have an informed sense 
of whether a belief is true or false and, if the latter, whether it is

of whether a belief is true or false and, if the latter, whether it is 
being held with delusional intensity. A key element in the decision 
is a comparison between the patient’s current beliefs and those he 4.4 persistent delusional symptoms and disorders

SECTION 4  clinical syndromes of adult psychiatry 612
habitually held, and here a corroborative account from an informed 
outside source is usually necessary.
The observer’s educated suspicion that a delusion is present is 
the starting point, but it is evident that that suspicion has to be aroused by the context of the apparently delusional idea because, no matter how isolated it appears to be, it nearly always occurs in the setting of a mental disorder whose other features may indicate a speciﬁ  c psychiatric diagnosis. Illogically, instead of recognizing 
the delusion and using it to make a deﬁ  nite diagnosis, we develop 
the conviction that we are dealing with a probable psychosis and thereafter judge all the patient’s utterances in light of that. While he may indeed be experiencing delusions, it is essential that we do not automatically assume that anything the psychotic indi-vidual says has of necessity to be of a delusional nature.

We must accept that we cannot be absolute in our recognition 
of a delusion. In addition to the illness context we base our esti-mate on a series of nuances, no one of which is pathognomonic but an accumulation of which becomes increasingly convincing. The abnormalities to be sought are as follows:
 1 An idea or belief is expressed with unusual persistence or force.
 2  As far as we can tell, the idea is not typical of the individual’s 
previously prevailing thinking and is not shared by his or her social community.
 3  The idea appears to exert an undue inﬂ  uence on the person’s 
life and consequently the way of life is altered to an extraordi-nary degree.
 4  Despite the signiﬁ  cance to the patient of the belief, he or she 
often displays secretiveness or resentment when questioned about it.
 5  The individual tends to be humourless and oversensitive about 
the belief.
 6  There is a quality of ‘centrality’; no matter how strange the

5  The individual tends to be humourless and oversensitive about 
 6  There is a quality of ‘centrality’; no matter how strange the 
belief or its consequences, the patient rarely questions that incredible things are happening to him or her. For example, why should a perfectly ordinary harmless person be singled out for constant surveillance by the security agencies? But this is simply accepted.
 7  Attempts to contradict the belief are likely to arouse an inap-
propriately strong emotional reaction, often with irritability and hostility and with a superciliousness that may be a form of grandiosity.
 8  On reﬂ  ection the belief appears unlikely to the observer, but at 
the time of history-taking the vehemence of its expression may temporarily disguise its improbability.
 9  The patient is so emotionally overinvested in the idea that 
it swamps other elements in the psyche, and many everyday activities are neglected.

9  The patient is so emotionally overinvested in the idea that 
10  If the delusion is acted out, uncharacteristic behaviours, 
sometimes involving violence, will occur which may be partly understood in terms of the abnormal belief.
11  Others who know the patient well will usually observe that his 
or her thinking and behaviour are alien, unless folie à deux
is present when, paradoxically, the other person’s denials of abnormality are themselves possible conﬁ  rmation of the pres-
ence of delusion.12  An odd feature of delusions is that, no matter how strongly  
they are held, when the patient is given the opportunity to obtain real proof he or she persistently evades accepting the opportunity.
13  One must always look for the features which frequently  accom-

pany delusions, especially suspiciousness, hauteur, grandiosity, evasiveness, and eccentric or threatening behaviour, as well as evidence of thought disorder, mood change, and hallucinations.
Particular features of delusions in 
delusional disorder
In addition to any of the above, in delusional disorder we ﬁ  nd several 
other elements, which are of importance in leading to the diagnosis:
1 The delusional system is stable and is expressed or defended with 
intense affect and with highly rehearsed arguments. The form of logic used by the patient is very consistent but the propositions 
are based on false premises. Since the individual is so focused on his beliefs and is so self-assured, he often succeeds in making the enquirer feel inept.
2 The delusional system is markedly ‘encapsulated’ , so that the 
beliefs therein and their accompanying symptoms are to a con-

siderable extent separated from the rest of the personality which retains a good deal of normal function. However, the compelling 
force of the delusions often overshadows these normal aspects and this is increasingly so with advancing chronicity of the ill-ness, when the tendency to express and act out the delusions may well increase.
3 When the individual is preoccupied with the delusional system 
there is strong emotional and physiological arousal, but when he 
or she is engaged on neutral topics, the arousal abates and an ordinary conversation can take place. Switching between normal and abnormal ‘modes’ , sometimes very rapidly, is virtually pathognomonic of delusional disorder.
4 Because of the encapsulation of the delusions and the normal–
abnormal switch just described, the patient may have phases of

abnormal switch just described, the patient may have phases of 
relative normality interspersed with psychotic periods. The switch can occur spontaneously or as a result of external provo-cation; the two are difﬁ  cult to disentangle because the hyper-
vigilant individual may perceive provocation in almost anything. Since it is a chronic illness the symptoms never remit, but if they are temporarily in the background the patient may converse and function almost normally and may have sufﬁ  cient quasi-insight 
to keep the delusions concealed for the moment. T otal denial of mental abnormality and resistance to psychiatric referral are almost universal in cases of delusional disorder and lead to severe underestimation of the illness’s frequency.
5 As a result of the features just described, many delusional disor-

der patients can continue to exist in society, sometimes with very abnormal but harmless beliefs but in other instances with highly malignant delusions, which they may or may not act out.
6 As will be repeatedly emphasized, delusional disorder must be 
diagnosed on the form  of the illness and the content of the delu-
sion is not used to make the primary diagnosis. On the other hand, the particular content is employed to categorize into sub-groups, as will shortly be described.

613
Delusional disorders: clinical features
Ofﬁ cial diagnostic criteria
The DSM-IV and ICD-10 criteria are shown in Tables 4.4.1 and 
4.4.2, respectively.
As will be seen, the DSM-IV and ICD-10 descriptions are very 
similar in overall outline but with a number of rather striking minor differences. The following speciﬁ  c items should be noted:
1 DSM-IV uses the term ‘non-bizarre’ delusions; this criterion has 
been shown to have little or no validity.
(11)
2 DSM-IV allows the presence of tactile and olfactory hallucina-
tions, while ICD-10 mentions only auditory hallucinations; in practice most modalities may be represented but the important point is that they are relatively non-prominent and usually paral-lel to the content of the delusion(s).
3 DSM-IV says that delusions should have been present for

3 DSM-IV says that delusions should have been present for 
1 month and ICD-10 insists on 3 months. Both are guesses, but ICD-10 is probably right to err on the side of caution and it pro-vides category F22.8 as a temporary niche until the deﬁ  nitive 
diagnosis emerges.
4 Both classiﬁ  cations exclude delusional illnesses due to organic 
brain disorder, medical illnesses, medication effects, or psycho-active substance abuse. In essence this is correct, especially in an illness of acute onset. However, as will be noted later, an apparently typical delusional disorder may arise as a long-term complication of any of these factors.
5 DSM-IV and ICD-10 agree emphatically that delusional disorder 
is not schizophrenia and DSM-IV notes that general functioning is not impaired. Both say that mood disturbance may accompany the delusional illness but is not a cause of it.
6 The list of subtypes according to delusional content is similar in

6 The list of subtypes according to delusional content is similar in 
both classiﬁ  cations, although ICD-10 adds self-referential and 
litigious themes.
7 Neither classiﬁ  cation speciﬁ  es that the essence of delusional 
disorder is a highly organized delusional system, largely encapsu-lated from normal aspects of the personality, although DSM-IV hints at this when it comments that functioning is not markedly impaired and behaviour is not obviously odd or bizarre. Neither comments that the patient can demonstrate alternating ‘normal’ and ‘delusional’ modes.
8 The ICD-10 category of ‘other persistent delusional disorders’ is 
vaguely described and is largely a catch-all heading or, as men-tioned above, a temporary holding station. However, it could conceivably be used for the time being to subsume the unofﬁ  cial 
delusional disorder diagnoses of paraphrenia and delusional misidentiﬁ  cation syndrome.
9 Overall, DSM-IV and ICD-10 give rather laconic descriptions

9 Overall, DSM-IV and ICD-10 give rather laconic descriptions 
of delusional disorder and it will be necessary to ﬂ  esh them 
out with relevant clinical details. This will be done after the next section on aetiological considerations.
General aetiological considerations in delusional 
disorders
It must be stressed that knowledge of aetiology in delusional 
disorder is scanty and highly speculative, largely because so little modern research has been conducted. What follows is an outline, Table 4.4.1  DSM-IV delusional disorder (297.1)
Principal features
(a) Non-bizarre delusions of at least 1 month’s duration(b)  Criterion A for schizophrenia has never been met, although tactile and 
olfactory hallucinations may be acceptable if they are related to the delusional theme
(c)  Apart from the impact of the delusion(s) or its consequences, functioning

(c)  Apart from the impact of the delusion(s) or its consequences, functioning 
is not markedly impaired and behaviour is not obviously odd or bizarre
(d)  Concurrent mood episodes, if present, are brief relative to the duration of 
the delusional disorder
(e)  The disturbance is not the direct outcome of a drug or medication or of a 
medical disorder
Subtypes
Erotomanic
GrandioseJealousPersecutorySomaticMixed (allowing for the presence of more than one of the foregoing)Unspeciﬁ  ed or otherTable 4.4.2  ICD-10 persistent delusional disorders
Delusional disorder (F22.0)
Principal features(a)   A delusion or set of related delusions, other than those described 
as typically schizophrenic, must be present; the most common are 
persecutory, grandiose, hypochondriacal, jealous, or erotic
(b) The delusion(s) must be present for at least 3 months

(c) The general criteria for schizophrenia are not fulﬁ  lled
(d)  There are no persistent hallucinations, but there may be transitory or 
occasional auditory hallucinations that are not speaking in the third 
person or making a running commentary
(e)  Depressive symptoms or episodes may be intermittently present, but the 
delusional symptoms must persist at times when there is no disturbance 
of mood
(f)  There must be no evidence of primary or secondary organic mental 
disorder or of a psychotic disorder due to psychoactive substance use
Subtypes
PersecutoryLitigious
Self-referential
GrandioseHypochondriacalJealousErotomanic
Other persistent delusional disorders (F22.8)
This is a residual category for persistent disorders with delusions that do not

This is a residual category for persistent disorders with delusions that do not 
fully meet the criteria for delusional disorder or schizophrenia. Illnesses with 
prominent delusions accompanied by persistent hallucinatory voices or by psychotic symptoms insufﬁ  cient to satisfy the criteria for schizophrenia are 
included here. A delusional disorder of less than 3 months’ duration is coded 
under Acute and Transient Psychotic Disorders (F23) until proven otherwise.4.4 persistent delusional symptoms and disorders

SECTION 4  clinical syndromes of adult psychiatry 614
and certain other factors will be noted when we come to consider 
some of the illness.
(a) Genetic factors
Changes in deﬁ  nitions of paranoia/delusional disorder over the 
years and the frequent confusion with schizophrenia make most studies all but impossible to interpret. Conclusions are inferential rather than evidence based. However, it seems well established
(12)
that delusional disorder and paranoid schizophrenia are less dir-ectly inherited than other forms of schizophrenia, and that there is little or no evidence of a genetic link between delusional disorder and schizophrenia.
There may be genetic links with certain severe personality disor-
ders, especially of the paranoid and schizoid varieties, but these are difﬁ cult to substantiate. There does seem to be an excess of such

ders, especially of the paranoid and schizoid varieties, but these are difﬁ cult to substantiate. There does seem to be an excess of such 
disorders in relatives and premorbidly in delusional disorder patients themselves. It is suggested that paranoid and schizoid traits are particularly liable to lead to social isolation and aggravation of delusional tendencies.
(13,14)
(b) Organic brain factors
Recent evidence from the study of delusional misidentiﬁ  cation 
syndrome (see later) indicates that delusions of a very speciﬁ  c type 
may arise in association with certain well-deﬁ  ned brain insults. 
There are strong hints, but much less supportive evidence, to sug-gest that organic brain factors may also be important in cases of delusional disorder. For example, head injury may lead to the devel-opment of marked paranoid symptoms, and there is a long-established association between chronic alcoholism and path-ological jealousy.
(15) Old age itself may be linked to the onset

(15) Old age itself may be linked to the onset 
of symptoms typical of delusional disorder, and early evidence of brain changes, especially in subcortical areas, is starting to appear in studies of various kinds of senile ‘paranoid’ illness.
(16–18)
Amphetamine and cocaine abuse(19) can induce delusional illness, 
as can therapeutic drugs, including l-dopa and methyldopa,(20)
at times. Delusional illness induced by the brain effects of AIDS 
infection has been documented.(21)
Gorman and Cummings(22) have proposed that delusional 
illnesses of organic origin have underlying features in common, particularly temporal lobe or limbic involvement and an excess of dopamine activity in certain areas of the brain.
If organic factors predominate in a particular case, delusions

If organic factors predominate in a particular case, delusions 
must be seen as a secondary feature of an organic brain disor-der. However, if the organic factors are subtle and of long dura-tion, the clinical appearances may be those of a quite typical delusional disorder which, interestingly, may well respond to neuroleptic treatment as effectively as idiopathic cases. (In fact, ‘idiopathic’ may simply denote organicity at a more subtle level.) It is very possible that organic brain factors are much more common than we suspect in delusional disorder, especial-ly in young males who have previously abused alcohol or drugs 
or have suffered a head injury in the past, and in older patients 
(more commonly female) who suffer from effects of an ageing brain.
(23,24)
(c) Interplay with mood factors

(23,24)
We have already seen that DSM-IV and ICD-10 agree that mood symptoms may accompany delusional disorder but not cause it. Delusional and mood disorders are separate illnesses with their own natural histories and responses to treatment, yet there is a complex relationship between them, as is also the case with mood 
disorder and schizophrenia. For example, it is well documented

disorder and schizophrenia. For example, it is well documented 
that some cases of apparently typical mood illness, unipolar or bipolar, can progress to delusional disorder or schizophrenia over time. Conversely, cases which appear to be delusional disorder but with an episodic course may prove to be bipolar illness. There are a number of anecdotal reports of delusional disorder responding to antidepressant treatment, and it is more than likely that these rep-resent a failure to recognize the true nature of a mood disorder associated with delusions.
Both depressive disorder and mania may be complicated by

Both depressive disorder and mania may be complicated by 
delusions. On the other hand, mood symptoms, especially dyspho-ria with anxiety, are a common complication of delusionaldisorder, while individuals with the grandiose subtype may show elation, which mimics mania but is far more sustained. Inrecovering delusional disorder, one may see postpsychoticdepression of varying degrees of severity and this is describedlater. Suicide is not unknown in delusional disorder but itsfrequency is undetermined.
In many delusional disorder patients the illness is profoundly 
isolating and sets them at odds with the rest of the society, which often generates suspiciousness, dejection, anxiety, and agitation in the individual. It seems that a vicious circle results whereby the delusion induces distress and physiological overarousal which, in turn, reinforces the strength of the delusion and progressively diminishes reality input.
(d) Psychodynamic theories of causation

The psychodynamic literature continues to discuss aspectsof  ‘paranoia’ but often fails to differentiate clearly between trait, symptom, personality disorder, and psychotic illness. Mostof the emphasis is on the persecutory aspect of paranoia, with only occasional references to other types of delusional content. Since psychotherapists rarely treat psychotic patients, theirexperience of delusional phenomena must actually be rareand their knowledge of the features correspondingly scanty. Their theoretical bias is to interpret the origins of paranoia in terms of psychological maldevelopment, ignoring the increasing weight of evidence that faulty brain mechanisms are involved. One must read the psychoanalytic literature on this particular topic with an ultracritical attitude, since it usually fails toprovide adequate illness deﬁ  nitions or clear case reports and 
generates explanatory theories which are unjustiﬁ  ably presented 
as proven facts.

(e) Conclusions regarding aetiology
No systematic research on paranoia took place for more than half a century and modern investigations into delusional disorder are only beginning to appear. Therefore it is premature to propose specific aetiological theories. However, a gathering weight ofevidence does suggest a localized and relatively circumscribedbrain disorder associated with the possible inﬂ  uence of abnormal 
neurotransmitter activity, probably involving dopamine overactiv-ity. Whatever the original basis of delusional disorder, it certainly seems that provocative inﬂ  uences such as head injury, alcohol 
abuse, and ill effects of drugs may play a part, whereas speculation about psychological causations suggest that this is at most a sec-ondary inﬂ  uence. There is an urgent need for the study of extended

case series utilizing modern neurophysiological and neuropsycho-logical investigative methods.

615
Delusional disorder: general features and 
introduction to the subtypes
We have already outlined the diagnostic criteria for delusional disor-
der in DSM-IV and ICD-10 and have ampliﬁ  ed these with descrip-

tions of many of the clinical phenomena associated with the illness. It has been emphasized that this is a stable and readily recognizable disorder, provided that the clinician is informed of the essential cri-teria and has dealt with at least several cases to familiarize him- or herself with its very characteristic ‘feel’ . With this experience it becomes much more possible to delve under the prominent symp-toms related to delusional content and to discern the underlying form of the illness. However, it is the predominant delusional content in an individual case, and the symptoms and behaviours related to this, which decide how a patient will present for assess-ment. Therefore we shall consider the main subtypes in some detail. It cannot be stressed enough that these are not separate types of illness, but variants on a single psychopathological theme.
All cases of delusional disorder occur in clear consciousness and

All cases of delusional disorder occur in clear consciousness and 
have a stable and persistent delusional system which is relatively encapsulated. Since much of the personality remains remarkably intact, a considerable degree of social functioning is retained in many cases. The patient experiences a heightened sense of self-reference within the delusional context and ordinary events take 
on unusual signiﬁ  cance. He or she clings to the delusion with fervid 
intensity and spurns any suggestion that a mental illness is present. Outside the delusional system the patient shows quite normal thinking, affect, and behaviour, but there is a marked tendency for gradual pushing to one side of these normal aspects. The retention of such a degree of normality makes the illness totally different from schizophrenia.
Earlier it has been indicated that the DSM-IV criterion of

Earlier it has been indicated that the DSM-IV criterion of 
non-bizarreness is unhelpful, although in all cases of delusional disorder the delusions are relatively well structured, coherent, and consistent, and the logic would often be acceptable if it weren’t that its basic premises are irrational. Many affected individuals can maintain overtly normal activities, at least in public, but increasing pressure of the delusion tends to cause corresponding responses in behaviour; these may be channelled socially, as in hypochondria-cally deluded patients who utilize medical resources, albeit exces-sively, or antisocially, as in the aggression of the jealously deluded individual. Mood abnormalities are common as a response to the effects of the illness.
Hallucinations do occur in some cases and may affect any modal-
ity, but they are often difﬁ  cult to assess and to differentiate from

ity, but they are often difﬁ  cult to assess and to differentiate from 
delusional misinterpretations and illusions. Widespread persistent hallucinations in more than one sensory sphere should make one cautious about the diagnosis of delusional disorder.
The illness appears to affect men and women approximately 
equally, but it is not clear if this is true of all subtypes. Despite older assertions that the illness is restricted to the middle-aged and elderly, 
the age of onset can actually be from late adolescence to extreme 
old age, with male patients appearing on average to experience earlier initiation. Some patients behave in an eccentric or fanatical fashion and, as a group, delusional disorder sufferers are excessively likely to be unmarried, divorced, or widowed, probably reﬂ  ecting

restriction of affective responses and some isolative tendencies. Despite this, the condition can be compatible with marriage and continued employment. The premorbid personality is usually described as asocial and there may indeed be an excess of long-
standing schizoid and paranoid personality disorders. However, when a patient makes a good recovery there may be little evidence of this, and it is possible that in some cases a ‘personality disorder’ is actually the prolonged and insidious prodrome of the illness.
Onset may be gradual or acute. In the latter the patient often 
identiﬁ  es a precipitating stressor, which is difﬁ  cult to conﬁ  rm (e.g.

identiﬁ  es a precipitating stressor, which is difﬁ  cult to conﬁ  rm (e.g. 
the person who has a delusion of skin infestation may attribute it to a single insect bite many years previously). While most indi-viduals are secretive about their abnormal beliefs or express them by such means as physical complaints or legal processes, a certain number actually utilize them, perhaps within the context of an extreme religious sect or by becoming an excessively insistent agitator on some social issue. Disinhibited and overtly aggressive behaviour seems more likely to occur in males, at times leading to clashes with the authorities.
In all cases of delusional disorder, no matter what the nature of

In all cases of delusional disorder, no matter what the nature of 
the delusional theme, the investigator should look for the relatively unique feature of the illness—the patient’s ability to move between normal and delusional modes of thinking. In the former there is relatively calm mood, reasonable rapport, and appropriate emotionalresponses, whereas in the latter there is overalerting, suspicious-ness, and the sense that the person is being remorselessly driven by 
the delusional beliefs. This situation is difﬁ  cult for the inexperi-

enced observer to comprehend, since it is inconceivable to most people that someone who can appear perfectly rational at one moment can almost instantaneously change to a possessed irratio-nal being—and then back again just as quickly. In a sense the same patient is both sane and insane, and when in the latter mode may be ultrapersuasive about the acceptability of his or her beliefs. One may imagine the plight of a lawyer faced with a client who has committed some uncharacteristically outrageous act as a result of a delusion, who can then discuss his case with apparent insight and logic, and even genuine remorse, but who nevertheless remains totally self-justifying. As a corollary, the client will usually deny the possibility of mental illness and often refuses to cooperate with psychiatric assessment. He may also refuse to cooperate with the legal process, to his knowing detriment.

Delusional disorder, when it was known as paranoia, often had a 
bad reputation because patients were regarded as angry, suspicious, accusatory, and potentially violent. Some undoubtedly are, but as we consider the various subtypes nowadays we realize that many sufferers, perhaps the majority, lead lives of internalized despair in progressively isolated circumstances. Anger and suspiciousness are often secondary, at least in part, to the perceived neglect of their overwhelming concerns. The illness is chronic and self-reinforcing, and it is likely that only a minority of cases are recognized or helped. Psychiatry does not have an impressive record of helpful-ness towards this group of patients.
The subtypes of delusional disorder
As previously noted, DSM-IV recognizes ﬁ  ve main subtypes based 
on the predominant delusional themes: the erotomanic, grandiose, jealous, persecutory and somatic, plus mixed and unspeciﬁ  ed types.

on the predominant delusional themes: the erotomanic, grandiose, jealous, persecutory and somatic, plus mixed and unspeciﬁ  ed types. 
ICD-10 also recognizes these subtypes, and adds litigious and self-referential categories. Here, the litigious variety is included within the persecutory group and self-referential cases are not given separate status since self-reference is, in reality, a feature of the illness as a whole and prominent in all cases.4.4 persistent delusional symptoms and disorders

SECTION 4  clinical syndromes of adult psychiatry 616
When delusional disorder was resurrected in DSM-IIIR, single 
delusional themes were emphasized, but the mixed categoryin DSM-IV accepts the reality that, for example, a hypochondriacal individual can also feel persecuted and an erotomanic patientcan be extremely grandiose. Also, we shall ﬁ  nd that there are
considerable individual variations within the overall themes,so that in the somatic subtype there are cases involving different body systems. Y et the range of major themes does not appear tobe all that wide and we have no explanation for this relativerestriction in their number. The ‘unspeciﬁ  ed’ category in DSM-IV 
allows us to accommodate any case whose delusional theme is unusual and leaves a door open to the discovery of other themesin the future.
In presenting the subtypes, relatively more attention will be given

In presenting the subtypes, relatively more attention will be given 
to the somatic form. This should not be taken as an indication that this is the most common variant; rather, it happens to be the one which has been best documented in the recent psychiatric litera-ture. Other types of delusional presentation are much more often described in non-psychiatric and non-medical sources, where the fundamental nature of the illness may be overlooked, and so we are only beginning to correlate such descriptions with modern ﬁ ndings on delusional disorder.
Delusional disorder: persecutory 
and litigious subtypes
In most people’s minds the persecutory type of delusional disorder 
is the archetype of ‘paranoia’ and it is usually assumed that it is the most common variety. Therefore it is surprising to ﬁ  nd that the

is the archetype of ‘paranoia’ and it is usually assumed that it is the most common variety. Therefore it is surprising to ﬁ  nd that the 
literature, while full of speculation, is very lacking in good descrip-tions of the phenomenology of the illness and, apart from unreliable psychoanalytic theory, says relatively little about persecutory delusions themselves.
By deﬁ  nition the illness is a chronic psychotic disorder with a well-

systematized delusional system and with relative sparing of the surrounding personality. The persecutory threats may be perceived simply as coming from ‘them’ , but can elaborate to descriptions of the most labyrinthine plots involving a variety of known and unknown adversaries. The beliefs are extremely stable and usually increase in complexity with the passage of time. There is height-ened awareness and misinterpretation of neutral environmental cues and, not unnaturally suspiciousness, extreme anxiety, and irri-tability are present. Elements of grandiosity are not uncommon, with the individual accepting that he or she is the centre of focused and malignant attention that would be inexplicable to the normal person. As the illness progresses there is a tendency to involve an increasing number of people in the persecutory system, not uncom-

monly relatives, physicians, law-enforcement agencies, aspects of 
government, and others.
As with other subtypes of delusional disorder, many individuals 
are able to conceal their increasingly insistent delusions for some time, but because of fear of harm they are likely to isolate them-selves more and more. If they live alone they may come to be regarded as eccentrics, but if they remain in contact with society the suspicion and anger must eventually become evident, sothat interactions with family, social agencies, or the authorities become increasingly confrontational.
(24) Despite the reputation of‘paranoia’ for violence, only a small proportion of these individuals 
resort to threat or assault, but with those who do the danger may be profound as the individual is without reservation in his beliefs and will act as though genuinely under severe provocation. Disinhibition may at times be engendered by alcohol or drug use, which makes such situations even more volatile.

Even in a long-standing illness, islands of normal functioning 
remain; despite this there is little or no insight and the patient 
resists any psychological explanation for his beliefs. He usually 
refuses to see a psychiatrist voluntarily; many patients of this kind are encountered in a forensic setting only after an outburst of unac-ceptable behaviour and are minimally cooperative.
(25)
Litigious variety of the persecutory subtype 
(querulous paranoia)(26,27)
In some individuals with delusional disorder there is a profound 
and persistent sense of having been wronged in some way, and these people endlessly and repetitively seek redress, sometimes personally but often through the legal system. In a proportion of cases there may initially have been a genuine grievance and there may also have been unsatisfactory recompense, but the subsequent pursuit of ‘justice’ becomes never-ending and also becomes self-reinforcing because no satisfactory resolution is possible.

This group may not be large but it generates considerable media 
publicity. Reports of cases naturally tend to be in the literature of the legal profession, the law-enforcement agencies, and, to some extent, forensic psychiatry, but rarely from general psychiatry. Because the individual appears relatively high functioning apart from his delusional beliefs, the complaintive behaviour may be 
regarded as mere eccentricity for a long time. As in many cases of delusional disorder, the immediate complaint and behaviour may 
seem coherent and not unreasonable but over time their ongoing, never-ending, and extraordinarily demanding quality begin to raise the suspicion of severe underlying psychopathology.Even then, unless the person begins to be perceived as a threat, little may be done and prolonged harassment of ofﬁ  cialdom

and the legal system may be tolerated for surprisingly longperiods. In some national communities (e.g. Germany and the Scandinavian countries) there are legal provisions to stop ‘barra-try’ or unreasonable use of the law by declaring an individual a querulous litigant.
Goldstein
(28) has described three typical ways in which ‘litigious 
paranoia’ presents. The ﬁ  rst is the ‘hypercompetent defendant’

Goldstein
paranoia’ presents. The ﬁ  rst is the ‘hypercompetent defendant’ 
who knows and uses the letter of the law up to and beyond its lim-its but pays no heed to its spirit. The second is the ‘paranoid party in a divorce proceeding’ who is often consumed with jealousy and pursues vendettas against the ex-spouse, the lawyers on both sides, and even the judge. The third is the ‘paranoid complaining wit-ness’ who endlessly initiates litigation despite repeated adverse judgements. All such individuals pursue their grievances in a driv-en manner, see conspiracy in every corner, and are often quite unscrupulous in their single-mindedness, blatantly bending facts to ﬁ t with their beliefs. Since they hold the delusional belief with 
total conviction, they can accept no counterargument or contrary facts. In the past, persistent litigation was virtually a preserve of the rich, but many modern societies provide a variety of avenues

for complaintiveness and will even support complaint procedures, 
and so abnormally litigious behaviour appears to be on the increase.
(29)

617
Diagnosis of the persecutory subtype
All the features of a delusional disorder as previously described 
are present. In this subtype, wariness, irritability, suspiciousness, and threatening behaviour are especially prominent, and both impulsive and planned violence may occur. Gaining conﬁ  dence 
is extremely difﬁ  cult, but if this succeeds, the more normal aspects 
of the individual’s personality may become apparent and one may also perceive how chronically anxious and overalerted he or she is.
The illness must be distinguished especially from the following:
X paranoid schizophrenia
X paranoid and antisocial personality disorders
X substance-related disorders
X organic brain disorders, including early dementia and some 
epileptic disorders
X obsessive-compulsive disorder.

Virtually nothing is known of the frequency and distribution of persecutory delusional disorder. As with other subtypes it occurs in both sexes, but male cases are probably overreported because of a readier tendency to violence and antisocial acts. The literature is biased by the reporting of the most overt cases, often in the news media or through the courts. It is open to speculation how many cases avoid diagnosis; as noted, relatively few come to the clinical attention of psychiatrists other than in forensic work.

Delusional disorder is very chronic, and it is presumed that cases of the persecutory subtype are as likely as others to be lifelong and to show increasing psychopathology with the passage of time. In a proportion of cases there is always a risk of violence and illegal behaviour. Since cooperation with assessment and treatment is usually minimal, the overall ﬁ  gures for prognosis must be bad, but 
we have no reliable data to conﬁ  rm this.
Forensic complications(30,31)
If someone with a generalized psychotic disorder like schizophre-
nia becomes sufﬁ  ciently disorganized, functioning in the commu-
nity becomes impossible. In contrast, many delusional disorder patients retain a sufﬁ  cient grasp of reality to continue existing in 
society, sometimes indeﬁ  nitely. However, this does not imply that

society, sometimes indeﬁ  nitely. However, this does not imply that 
their illness is quiescent. Intellectual ability, capacity for reasoning, and the form of thought remain relatively intact, but the delusional process worsens. They retain the ability to brood on their beliefs so that normal thought processes and delusions interweave, as do normal and abnormal behaviours. Anger may express itself explosively, but some individuals carry out violent actions in a very calculated way, believing that a just vengeance is being exacted. Afterwards there may be real regret and a clear awareness of a wrong having been committed against society, but the actions are seen as justiﬁ  able and necessary. The patient is usually aware that 
by societal standards his deed is legally and morally wrong, but that

by societal standards his deed is legally and morally wrong, but that 
awareness resides within the normal non-delusional aspect of his mental functioning. Within the conﬁ  nes of the delusional system, the person unswervingly believes that it was obligatory for him to 
behave as he did.
In such cases, the judge and jury are placed in a quandary, made 
worse by the individual’s frequent arrogance (related to grandiosity), self-justiﬁ  cation, and ambivalent expression of regret. The ability

worse by the individual’s frequent arrogance (related to grandiosity), self-justiﬁ  cation, and ambivalent expression of regret. The ability 
to acknowledge the wrongness of one’s action in general terms and even to show remorse for it, while also asserting that it was neces-sary to carry it out, may well be regarded as indicating wilfulness or hypocrisy. Then, paradoxically, culpability may be determined by the content of the delusion, although this has minor relevance to the disinhibition of behaviour. Thus, as Goldstein has pointed out, if the person felt threatened because of a delusional belief and reacted, as he genuinely perceived, in self-defence, his degree of blame may be adjudged to be low. But if he were equally deluded and carefully plotted revenge, this might be seen as highly culpable. Such a distinction cannot be defended logically either in the clini-cal situation or at law.
Delusional disorder deﬁ  es any deﬁ  nition of insanity in black or

Delusional disorder deﬁ  es any deﬁ  nition of insanity in black or 
white terms; it is both black and white. Because few psychiatrists, 
even in the forensic ﬁ  eld, are familiar with its detailed characteris-
tics, psychiatry has had limited success in educating the legal pro-fession about the subtleties of the illness or the conundrum that delusions can induce such abnormal behaviour in an individual who superﬁ  cially appears rational and for signiﬁ  cant periods of 
time is effectively sane even though the illness is always lurking there.
Treatment of the persecutory subtype
Treatment is discussed later in this chapter in the section on overall treatment aspects.
Delusional disorder: somatic subtype 
(monosymptomatic hypochondriacal psychosis)
Modern society, especially in developed countries, is preoccupied

Modern society, especially in developed countries, is preoccupied 
with health concerns. While much of this is positive, there is no doubt that many people worry excessively about health matters and a proportion of these show pathological self-concern. This can shade into hypochondriasis, in which there is a persistent convic-tion of illness in the absence of objective evidence, with misinter-pretation of bodily sensations as disease and with inability to accept reassurances. In many cases the individual shows some degree of body image disturbance, sometimes of extreme degree.
(32) Usually 
we think of hypochondriasis as referring to physical complaints, but nowadays it seems that an increasing number of people are also liable to complain of psychological disorder.
Hypochondriasis is common and may be a personality trait, but

Hypochondriasis is common and may be a personality trait, but 
it can also be an accompaniment to many psychiatric illnesses, both delusional and non-delusional. It is the presenting feature of the somatic subtype of delusional disorder and in different patients we see many varieties of alteration of body image expressed in delusional terms. Certain themes of delusional content tend to predominate and this has meant an unfortunate proliferation of descriptive names scattered across a fragmented literature, lead ing 
to many difﬁ  culties in conceptualizing the subtype and in separat-
ing it from other psychiatric disorders with prominent hypochon-driasis. As with all subtypes of delusional disorder, the clinician 4.4 persistent delusional symptoms and disorders

SECTION 4  clinical syndromes of adult psychiatry 618
must bear in mind the advice already given that, for the diagnosis 
of delusional disorder, it is the characteristic form of the illness, which is of prime importance, not the content of the delusional beliefs. The hypochondriasis in delusional disorder may superﬁ  -
cially resemble that of somatoform disorder, psychotic depression, or obsessive-compulsive disorder, but careful investigation will reveal an illness very different from these.
We shall consider the manifestations of the somatic subtype under four major theme areas:
1 delusions involving the skin;2 delusions of ugliness or misshapenness (dysmorphic delusions);3 delusions of body odour or halitosis;
4 miscellaneous.
(a) Delusions involving the skin(33)
In the delusion of skin infestation, the patient insists that he has

In the delusion of skin infestation, the patient insists that he has 
organisms, usually insects, crawling over the surface of the skin and sometimes burrowing into the skin or under the nails. In most instances he cannot see the creatures, but sometimes there may be graphic descriptions. This may represent a visual hallucination but more usually seems to be a vivid ideational projection.
The delusion of parasites burrowing deeply under the skin is 
often attributed to worm-like parasites, and internal body sensa-tions or the rippling of small superﬁ  cial muscles are misinterpreted 
as evidence of their activities. Sometimes the patient believes that the worms have spread throughout the body or intermittently migrate from place to place.
In the delusion of discrete foreign bodies under the skin or nails, 
these bodies are occasionally described as inanimate, but generally

these bodies are occasionally described as inanimate, but generally 
the patient says they are seed-like or believes that they are parasite 
eggs. In some individuals this is associated with an irresistible urge to pick, and multiple deep excoriations may result. Such people are sometimes labelled as having ‘neurotic excoriations’ or factitious disorder, but in fact the picking behaviour is delusionally motivated and is an irresistible urge to stem the invasion of the parasites.
Chronic cutaneous dysaesthesia
(34) is an unremitting burning 
sensation of the skin or mucosae, sometimes generalized but at other times largely conﬁ  ned to complaints of glossodynia or 
vulvodynia. A minority of these patients appear to have a delusional disorder.
A subgroup of patients with trichotillomania and onychotillo-
mania
(35) have delusional illnesses, and the hair-pulling or nail-

mania
picking may be part of the attempt to rid themselves of parasites.
In all the above presentations, the delusion and its associated 
behaviours typically occur in the setting of many well-retained per-sonality features and the patient can often make very clear-cut and apparently rational complaints, convincing the many physicians they attend, at least for a time, that actual physical disease is present. However, no somatic treatment works and the complaining becomes increasingly shrill and unreasonable. The sufferer cannot be persuaded that infestation is not present and often becomes very angry at the perceived incompetence of the dermatologists he has visited.
Usually the story of the infestation is presented in great detail,

Usually the story of the infestation is presented in great detail, 
perhaps involving an original event such as an insect bite. ‘Proof’ is presented by displaying skin lesions, deformed nails, bald patches, 
etc. The ‘matchbox’ or ‘pill-bottle’ sign, in which the patient pro-duces a small container in which ‘insect corpses’ or ‘eggs’ are kept, is typical; the contents nearly always turn out to be dried mucus, skin scrapings, or pieces of lint. Often, there is incessant cleaning of self and surroundings, and repeated demands may be made to local authorities or pest-control agencies for disinfestation of the home. At times bizarre and even dangerous self-treatment is resorted to, such as applying boiling water or corrosive substances to the skin. The more normal part of the psyche is dominated by shame or fear of passing on the infestation, so that progressive social isolation tends to occur, with attendance on doctors as virtually the only outside activity.
(b) Dysmorphic delusions

‘Dysmorphophobia’ , an old term which implies a morbid fear of being deformed, is still sometimes employed to describe cases in this category but should be abandoned since it has been so loosely used to denote both delusional and non-delusional complaints as well as a variety of very different illnesses.
(36) In the present context 
we are considering only cases typical of delusional disorder, which present with a false belief of ugliness or deformity. In some instances there may indeed be some minor deformity, but the complaining and demand for alleviation are out of all proportion and expressed with delusional intensity.
A speciﬁ  c feature is often singled out by the complainer, such as

A speciﬁ  c feature is often singled out by the complainer, such as 
an overlong nose, prominent ears, over-large or undersized breasts, dissatisfaction with the appearance of the genitalia, a skin blemish, or some other. However, in other cases the total body is perceived as abnormal, and there is evidence that a small group of apparent cases of anorexia nervosa and bulimia nervosa may have an under-lying delusional disorder.
Many of the patients with dysmorphic delusions go from surgeon 
to surgeon demanding cosmetic procedures and usually being refused, but if the surgeon does not perceive the illogicality of the complaint an operation may take place. While some successes have been reported, the general consensus is that most cases need psy-
chiatric rather than surgical intervention and unnecessary opera-
tions may seriously worsen the mental disorder in the long term.
It is sometimes very difﬁ  cult to distinguish cases of delusional

It is sometimes very difﬁ  cult to distinguish cases of delusional 
disorder of somatic subtype from severe somatization disorder, and claims have been made that there is a continuum between these illnesses.
(37) The evidence for this is minimal and a diagnostic dis-
tinction is essential since treatments of the two disorders are very 
different.
(c) Delusion of smell or of halitosis(38)
In this category it is often very difﬁ  cult to distinguish between

In this category it is often very difﬁ  cult to distinguish between 
delusions and hallucinations of smell or taste. The term ‘olfactory reference syndrome’ is often used to describe olfactory delusions, but in fact it should properly only refer to hallucinatory experiences. Sometimes the deluded patient will say that he or she has not actually experienced the odour, which is usually unpleasant, but ‘knows’ that it is present because of remarks made by others or their avoidant behaviour. In other cases the stench is described graphically and consistently (like ‘burning rubber’ or ‘faeces’) and here a hallucination may be present. There may be no explanation, or else the smell may be attributed to escaping ﬂ  atus, abnormal 
sweat secretion, or sinus or dental problems leading to halitosis

619
etc. As is typical, an unending and escalating search for a physical 
cure occurs.
(d) Miscellaneous delusional contents
Presumably there is an almost inﬁ  nite possibility of different 
themes, but in practice their numbers are somewhat limited. The following have been described.
(i) Dental
Although his dentition is satisfactory, the patient insists that his dental bite is abnormal and obtains repeated corrective treatments from successive dentists, none of which works. This has been termed the ‘phantom bite syndrome’ , and may sometimes be asso-ciated with complaints of facial pain for which no physical basis is apparent. There may also be delusional complaints of deformity of the jaw or abnormality of the temporomandibular joint.
(ii) Delusion of transmitting non-sexual diseases
Some patients may be convinced that they are causing illnesses in others (e.g. tuberculosis), and they will cite as evidence, for example, that everyone starts coughing when they enter a room.

(iii) Delusion of sexually transmitted disease(39)
Hypochondriasis is, of course, rampant around the topic of sexu-ally transmitted disease. A subgroup of delusional disorder patients develop the conviction that they have venereal disease, often when there is no evidence of risk-taking behaviour having occurred. In the past syphilis was probably the greatest fear, but nowadays it is usually AIDS. Repeated tests showing negative serology have no reassuring effect. Interestingly, a few cases of actual AIDS have been described in which a delusional illness with hypochondriasis has emerged, usually due to direct effects of the virus on the brain.
Differential diagnosis of delusional 
disorder: somatic subtype
First, the presence of a signiﬁ  cant physical disorder must be excluded

First, the presence of a signiﬁ  cant physical disorder must be excluded 
(although it is possible for a physical illness and delusional disorder to coexist). The illness must be distinguished from the following:
X substance-related disorders (e.g. itching related to alcohol-related 
liver failure, cocaine abuse, etc.)
X organic brain disorders
X severe depressive disorder with hypochondriacal delusions
X somatoform disorders, especially body dysmorphic disorder
X obsessive-compulsive disorder
X factitious disorder

Cases usually present in medical and surgical practices and much less often in a psychiatric context. We have no idea of the frequency because non-psychiatrists make a variety of diagnoses, often untranslatable in psychiatric terms. However, the somatic subtype of delusional disorder is certainly not uncommon, and this is increasingly being revealed as consultation–liaison psychiatry develops.These cases make a strong impression on physicians and surgeons

because of their insistence and unreasonable demands. T o date, dermatologists have been most aware of the nature of the delusional complaining and, in some cases, have learned to treat the deluded patients satisfactorily with appropriate medication. Infectious and tropical disease specialists also have an awareness, as do gastro-enterologists and some dentists, and they are gradually referring more cases for psychiatric help. Plastic and cosmetic surgeons see a considerable number of cases with dysmorphic delusions, but it is still rather uncommon for them to seek psychiatric consultations. Since the patient with delusional disorder generally refuses to visit a psychiatrist willingly, it is often necessary for us to consult on the other specialists’ territory in order to offer practical help and to obtain a better idea of the illness’s frequency.
From what we know, the somatic subtype affects both sexes

From what we know, the somatic subtype affects both sexes 
approximately equally and the age of onset may be from late ado-lescence to extreme old age. The illness is more common in the unmarried, divorced, and widowed.
Typically the illness is long term with a tendency to worsen with time. Some patients eventually lapse into a rather apathetic state, and some attempt or commit suicide in chronic despair, but the majority continue to move from doctor to doctor demanding treat-ment on their own deluded terms.
Treatment of the somatic subtype
Treatment is discussed later in this chapter in the section on overall treatment approaches.
Delusional disorder: jealousy subtype(40)
This is sometimes known as the Othello syndrome, but the term is not recommended as it lacks speciﬁ  city.
The phenomenon of jealousy
Jealousy can arise in various contexts, but here we shall deal with 
sexual jealousy. This is a virtually universal human emotion, espe cially

when a rival is attempting to lure away someone’s sexual partner. Males and females are equally prone to jealousy but may express it differently; Mullen and Martin
(41)suggest that men are mainly con-
cerned with losing the partner whereas women worry about the effect of inﬁ  delity on the ongoing relationship.
Broadly there are three levels of jealousy. Normal jealousy is 
understandable in terms of the situation and the individual’s perception of it, and its expression can range from pique to severe rage. How it is expressed is largely related to temperament; some people habitually vent anger with slight provocation and others usually bottle up their feelings. On the whole, men tend to act out their jealous anger more physically.
Neurotic jealousy occurs where the mood and its mode of expres-

sion are relatively normal but owing to non-psychotic psychiatric illness, including personality disorder, the reaction is impulsive and excessive. Although the individual is reacting to an overvalued idea rather than a delusion, this type of jealousy can be irrational and 
quite persistent, and may be expressed dangerously.
Psychotic jealousy, as in delusional disorder, is characterized by 
a ﬁ xed delusional belief which cannot be swayed by reasoned 
argument or presentation of contrary evidence. This is the most 4.4 persistent delusional symptoms and disorders

SECTION 4  clinical syndromes of adult psychiatry 620
alarming type since there is no dissuasion and there is an inexora-
bility about the way that the individual accuses, controls, and even stalks the victim. Since the accusations are usually untrue, the latter is bewildered by them, but occasions do arise when a partner actu-ally has been unfaithful and it is then very difﬁ  cult for the observer 
to know at ﬁ  rst how much of the jealousy is justiﬁ  ed and how much 
is delusional. Eventually the savageness and unreasonableness of the accusations reveal themselves as undoubtedly abnormal, but 
meanwhile a frightened partner will have suffered enormous abuse and possibly repeated assault.
When does jealousy become pathological?

Jealousy, which appears justifiable is regarded as normal, although perhaps not laudable, and it will usually be accepted by society if its manifestations are not antisocial. Nowadays we increasingly disapprove of jealous violence, whether provoked or not, but in some communities there is still acknowledgement of thecrime passionel , the crime committed out of jealous love. 
However, this is an excuse extended only to males, and thejealous woman who commits assault or murder is usually treated more harshly.
Cobb
(42) proposed the following as clinical features of pathologi-
cal jealousy, whether it be neurotic or psychotic.
1 The jealous thinking and behaviour are unreasonable in expres-
sion and intensity.
2 The jealous individual is convinced of the partner’s guilt but the 
evidence is dubious to others.

3 A recognizable psychiatric illness is present which could plausibly 
be associated with abnormal jealousy.
4 In a proportion of cases, the jealous person has habitual 
personality characteristics of jealousy, suspiciousness, and overpossessiveness.
5 The jealousy persists unduly and reinforces itself.6 Pathological jealousy is usually focused on one speciﬁ  c person.
In neurotic jealousy, which in some ways resembles obsessive-

compulsive disorder, there is high self-awareness of the emotion and sometimes of its irrationality. In delusional jealousy the person is totally at one with the belief, which has come to occupy much of his or her time. Counterargument or contrary evidence is rejected, yet in delusional disorder the individual may be so high function-ing that he or she is totally convincing to outsiders and may even be able to brainwash the innocent victim into admission of guilt, a form of folie à deux .
The impact of pathological jealousy
Delusional jealousy is anguishing to the sufferer and even more so 
to the sexual partner who is accused of inﬁ  delity. The latter is sub-

jected to escalating emotional abuse, and indignation, protest, and proof of innocence are unavailing. Physical violence, especially by males, is common
(43) and in a proportion of cases ﬁ  nally ends in 
homicide, sometimes followed by the suicide of the perpetrator.(44)
Subjected to prolonged threat, many victims are too terriﬁ  ed to 
speak up, and some become housebound in a vain attempt to pre-vent accusations of philandering. From time to time the situation reveals itself when the desperate partner attempts suicide and talks to a helping professional when recovering.Clinical features
The person’s belief in the other’s inﬁ  delity is absolute and brooks

The person’s belief in the other’s inﬁ  delity is absolute and brooks 
no contradiction. There is much associated irritability, despondency, and, in some cases, aggressiveness. An ever-increasing proportion of time is spent searching for spurious ‘proofs’ , and ‘clues’ are pounced upon and misinterpreted; for example, an innocent stain is declared to be semen. The victim is put through endless interro-gations and is kept under constant surveillance.
Paradoxically, when the jealous individual is questioned closely 
about his or her speciﬁ  c charges, details prove vague, there is dis-
missiveness, and there are self-justifying repetitive assertions. Evidence is always about to be produced but rarely materializes. Strangely too, the jealous person often avoids taking the action, which might provide deﬁ  nite proof of guilt or innocence, and this 
passivity in the midst of intensiveness may be evidence of some volitional defect.
As noted, delusional jealousy is more commonly reported in

As noted, delusional jealousy is more commonly reported in 
men, but this is probably an artefact due to their greater likelihood of violence. Also, there is a link between chronic alcohol abuse, as well as amphetamine and cocaine abuse, and delusions of jealousy, and it is known that these substance abuses are more common in 
males.
The overall prevalence of abnormal jealousy and the specific 
prevalence of the delusional disorder subtype are unknown and, because of fear on the part of the victim, both are invariably underreported. Both heterosexual and homosexual cases occur, and family patterns of jealous behaviour have been described, but there is little evidence of direct inheritance.

The condition may appear gradually or suddenly, but even when the onset seems rapid there may have been a previous period of rumination and perplexity of varying duration. When the delusion crystallizes the perplexity vanishes and the patient is then totally sure of his belief.
Delusional jealousy is typical in being chronic and often lifelong. 
Without treatment the prognosis is poor and the danger to the victim is ever present. Most patients refuse psychiatric help and unfortunately may only receive it after incarceration for a violent crime.
The illness must be distinguished from the following:
X actual marital or sexual problems, including spousal inﬁ  delity
X mental handicap, where a simple-minded person may develop 
a ‘crush’ and be unable to understand that the other person does not reciprocate, or else enters into a sexual relationship and cannot cope with the partner’s motives and behaviours

X schizophrenia, especially of the paranoid type
X major mood disorder with delusions, either depressive or 
manic
X personality disorder, especially of the paranoid, antisocial, 
borderline, histrionic, and narcissistic types

621
X substance abuse (which may complicate any of the other differ-
ential diagnoses)
X organic brain disorders, including dementias and some epileptic 
disorders
X sexual dysfunction may lead to fears that a normal partner is 
seeking satisfaction elsewhere
It should be noted that an important part of the diagnostic
process, an accurate collateral history, may be impossible to obtain in cases of delusional jealousy because of the victim’s fears.
Forensic complications
In cases of identiﬁ  ed physical abuse in a relationship one possibility 
that must always be considered is delusional disorder of jealous type. Severe assault and even murder are not uncommon, and the physician has a duty to warn and protect the partner if these dangers seem real, perhaps divulging conﬁ  dential information if 
necessary. Of course the patient denies that his beliefs are unjusti-ﬁ ed and may present his case more convincingly than the terriﬁ  ed

necessary. Of course the patient denies that his beliefs are unjusti-ﬁ ed and may present his case more convincingly than the terriﬁ  ed 
victim can. If involuntary committal is necessary it may be very difﬁ cult to sustain, partly because of the individual’s ability to 
maintain a pseudonormal facade and often because he or she threatens litigation.
Occasionally, cases of stalking, usually of females by deluded 
males, are jealousy related and the victim is nearly always well aware of the stalker’s identity in these instances.
Treatment
This will be discussed when considering the overall treatment approach to delusional disorder. If successful treatment can be achieved, the couple may require considerable psychotherapy and counselling to re-establish a trusting and fear-free relationship.
Delusional disorder: erotomanic
subtype(45–48)
In erotomania the individual has strong erotic feelings towards

In erotomania the individual has strong erotic feelings towards 
another person and has the persistent, unfounded belief that this other person is deeply in love with him or her. The belief is usually delusional, though a small number of non-delusional cases have been reported. Occasionally the imagined lover does not actually exist, but more often he or she is a real person who is unaware of the situation. The phenomenon is often referred to as de Clérambault’s syndrome, but this usage is obsolete and can be misleading since it is used to describe erotomanic manifestations in a number of different mental illnesses.
In the older literature it was claimed that erotomanic delusions 
were largely conﬁ  ned to women, especially isolated and frustrated 
elderly spinsters, but more and more cases of male erotomania are being reported nowadays.
(49) In both sexes the majority of cases

(49) In both sexes the majority of cases 
described involve heterosexual emotions, but homosexual eroto-mania is now well documented in both males and females.
The patient yearns for another person and has the unshakeable belief that these feelings are reciprocated. The person is often socially unattainable, may be of higher social status, and can be a celebrity. There has rarely been close contact and the love object will usually be unaware of the situation, but despite this the patient believes that the other initiated the imagined relationship, often 
with covert signals or utterances. Many patients experience strong erotic, even orgasmic, feelings, but some insist that the ‘relation-ship’ is platonic and that the other person is maintaining a non-sexual attitude of watchful protectiveness.
In many instances the patient makes no attempt to get in touch

In many instances the patient makes no attempt to get in touch 
with the love object, perhaps writing letters or buying gifts but not sending them. When given a chance to make actual contact he or she will frequently avoid doing so and will make spurious excuses such as not wanting to offend the other person’s spouse. In those cases where the patient does attempt contact, false reasons are 
presented to explain the almost inevitable rejection that results.
Since this is erotomania in the setting of delusional disorder, the

Since this is erotomania in the setting of delusional disorder, the 
illness will have the typical form of a tightly knit delusional system with preservation of relatively normal personality features and with greater or lesser ability to continue functioning in society. There is often enough insight or inhibition present for the patient to keep the delusional beliefs concealed. However, at times he or she may be profoundly angered by being ‘inexplicably’ rejected and may act this out, occasionally dangerously. This is more likely to occur in males.
The onset of erotomania can be gradual or apparently sudden.

The onset of erotomania can be gradual or apparently sudden. 
Hallucinations are sometimes present but are not prominent, although the patient may be encouraged by ‘hearing’ the other person express passionate feelings. Occasionally, the presence of tactile hallucinations leads the patient to believe that a lover has paid a visit during the night (sometimes picturesquely referred to as the ‘incubus syndrome’).

Many covert examples necessarily go unrecognized and so there is a bias towards diagnosis of cases with some sort of acting out behaviour. Otherwise the most common situation is one where the patient, after years of silent suffering, becomes unhappy enough to be treated for depression and then, during sympathetic history-taking, lets the delusional belief slip out. There is often much accompanying anguish and perhaps anger, and of course the beliefs are regarded as indisputable. Obviously, if the patient has been very secretive, a conﬁ  rmatory history may be impossible to obtain. 
In married patients the spouse may be totally unaware of delusions which have lasted for years.
The following disorders may be associated with secondary eroto-
manic features:
X Schizophrenia, especially paranoid, in which the erotomania 
coexists with other delusions, ﬂ  orid hallucinations, and more 
widespread thought disorder.

X Major mood disorder, in depressive or manic phases.
X Organic brain disorders, including epilepsy, post-head-injury 
states, following long-term substance abuse, senile dementia, and possibly as a side effect of steroid treatment.
X Mental handicap, in which misunderstanding occurs regarding 
another’s feelings or intentions. However, we must remember that the mentally handicapped are liable to sexual abuse and we must not unthinkingly dismiss sexually laden remarks that they may make about other individuals. Conversely, we must also remember that mental handicap can coexist with psychotic dis-orders and delusional expressions.4.4 persistent delusional symptoms and disorders

SECTION 4  clinical syndromes of adult psychiatry 622
X Delusional misidentiﬁ  cation syndrome has occasionally been 
described with erotomanic features.
X Non-delusional erotomanic beliefs may emerge in unstable indi-
viduals, sometimes complicating transference in the course of psychotherapy. If associated with histrionic traits there may be ﬂ orid acting out, but the beliefs do not have the qualities of a 
delusion.
Nothing is known of the frequency of erotomania in general, or of the erotomanic subtype of delusional disorder. As will be noted 
below, the more dangerous aspects of the illness are proving to be not uncommon.
Without treatment this is a chronic illness, which is likely to worsen gradually over time.
Forensic complications(50)
Males who irrationally act out their erotomanic delusions are 
usually diagnosed as schizophrenic but some prove to have delusional disorder. Often the overt behaviour is in the nature of

usually diagnosed as schizophrenic but some prove to have delusional disorder. Often the overt behaviour is in the nature of 
harassment, but even without violence the individual’s persistent intrusiveness and incorrigibility can be thoroughly alarming to the victim, who is bewildered by the situation and by the other’s accusations of duplicity.
(51)
Severely aggressive behaviour can lead to assault, kidnapping, 
and even murder, sometimes of the love object but at other times of an acquaintance who is viewed as a rival. A manifestation, which has gained much recent publicity is that of victim stalking, and in a considerable number of cases the victim has no idea who is carrying out the stalking.
While women are generally less prone to aggressive acting out of

While women are generally less prone to aggressive acting out of 
their delusions, they may sometimes demonstrate their false beliefs in devastating ways. For example, a deluded woman may claim pub-licly that a physician, counsellor, or teacher has demonstrated strong erotic feelings towards her. This belief may be the result of a delu-sional memory. If she has an undeteriorated personality, is coherent, totally believes her own story, and presents it with typical vehemence and persistence, it may be virtually impossible to persuade the public 
and the authorities that the accusations are totally false. Any profes-
sional person dealing with deluded patients must be aware of abnormal transference emotions that may arise in the patient during treatment, usually of a heterosexual nature but sometimes homo-
sexual. Great circumspection is then required and the therapist must 
immediately seek collegial (and possibly legal) help.
Treatment

Treatment
Treatment is discussed later in the section on overall treatment of 
delusional disorder.
Delusional disorder: grandiose subtype(23)
This is the least well-described variant of delusional disorder, not surprisingly in view of its nature. An individual who is habitually elated, even exalted, and who may believe himself or herself rich or powerful is unlikely to seek help, especially psychiatric help. If he or she remains sufﬁ  ciently high functioning to remain in the community, the delusions may be undetected; indeed some people

capitalize on their beliefs by belonging to fringe organizations, apocalyptic religious groups, or doomsday sects. Sometimes these groups develop malignant qualities, especially under a deluded but charismatic leader, and one cannot minimize the dangerous quali-ties of the forceful megalomaniac whose grandiosity is alloyed with persecutory anger. Like-minded and impressionable people are readily drawn in and a kind of mass shared psychotic disorder may 
result; comparisons with Nazi Germany are not inapt.
This disorder often only becomes apparent over time and with 
observation. The few cases that we identify tend to fall into two categories. The ﬁ  rst are those whose state of bliss is so profound 
that they totally neglect self-care. The rest are usually seen in custody after they have committed an offence under delusional inﬂ  uence. 
The characteristic underlying features of a delusional disorder have already been well described.

The illness must be distinguished from the following.
X Mania, in which grandiosity is associated with euphoria, overac-
tivity, and, at times, irritability and suspiciousness. As the mood is often volatile and/or phasic, so the grandiose features are unstable.
X Schizophrenia in which there is marked incongruity between 
ecstatic affect and relative thought poverty.
X Organic brain disorders, especially affecting the prefrontal cere-
bral lobes, which cause labile mood, disinhibited behaviour, and some degree of cognitive deﬁ  cit. Cerebral syphilis (general paralysis
of the insane) used to be the best-known exemplar.
X Antisocial personality disorder in which the individual feels 
above the law and may express grandiose ideas and behaviours. In these cases one ﬁ  nds evidence of lifelong impulsivity, lack of

above the law and may express grandiose ideas and behaviours. In these cases one ﬁ  nds evidence of lifelong impulsivity, lack of 
remorsefulness, and usually a long history of delinquency.
We have virtually no information. The illness can occur in either sex and apparently at any age from adolescence onwards. It may appear gradually or suddenly.
As far as we know, the grandiose subtype is as chronic and unremitting as the other subtypes of delusional disorder. For many years the presence of grandiosity in any psychiatric disor-der has been regarded as a bad prognostic factor. In delusional disorder this may be so, because a grandiose delusional system is particularly likely to be associated with spurning of treat-ment. Even if treatment begins to be effective, the abandoning of highly pleasurable beliefs may not be welcomed by some patients.

There may be forensic complications if grandiose delusions are 
acted out.
Treatment
This is discussed later when considering the overall treatment of delusional disorder.

623
Delusional disorder: mixed and unspeciﬁ  ed 
subtypes
There is little to be added regarding these categories. In DSM-IV it 
is accepted that more than one delusional theme can exist side by side so that, provided that the form  of the illness is that of delusional 
disorder, it is acceptable to have combined themes of, for example, hypochondriasis and persecution, persecution and grandiosity, erotomania and jealousy, etc.
The unspeciﬁ  ed type is a residual category and again the illness 
must have the form of a delusional disorder, but the delusional content is one other than those speciﬁ  cally listed. No reliable data 
exist on either the mixed or the unspeciﬁ  ed subtypes.
Other disorders with persistent delusions
As mentioned previously, ICD-10 has a category for ‘other persis-
tent delusional disorders’ (F22.8), but this is too loosely worded

tent delusional disorders’ (F22.8), but this is too loosely worded 
to delineate any coherent clinical entity. Paraphrenia, as has been noted before (p. 283) is regarded by some, including the present author, to be a candidate for inclusion in an expanded category of delusional disorders but currently is not receiving ofﬁ  cial notice. 
Therefore, the only condition we shall consider here is delusional misidentiﬁ  cation syndrome.
Delusional misidentiﬁ  cation syndromes (DMIS)(52)
The abilities to recognize individual faces and to discriminate

The abilities to recognize individual faces and to discriminate 
between different faces are fundamental human processes and nor-mally we are extraordinarily adept at them. Changes in a familiar facial appearance can be unsettling and even frightening, in both children and adults. A great deal of sophisticated neurophysiologi-cal and neuropsychological investigation has been carried out on normal and abnormal face-recognition processes.
A number of clearly deﬁ  ned neurological disorders are associated 
with very speciﬁ  c abnormalities of face recognition.
(53) Here we 
shall emphasize those cases in which a delusion of misidentiﬁ  ca-
tion is the principal symptom of the disorder and in which the form or structure of the illness is in many ways similar to that of delusional disorder. These are the delusional misidentiﬁ  cation syn-
dromes. However, it is important to note that superﬁ  cially similar

dromes. However, it is important to note that superﬁ  cially similar 
presentations may occur as secondary features in cases of schizo-phrenia, severe mood disorder, or dementia, and in these we refer to a misidentiﬁ  cation phenomenon rather than syndrome.
(a) Clinical features
There are four main variants of DMIS:
1 the Capgras syndrome, in which the individual falsely perceives 
that someone in his environment, usually a close relative or friend, has been replaced by an almost exact double
2 the Frégoli syndrome, where the patient believes that one or 
more individuals have altered their appearances to resemble familiar people, usually to persecute or defraud him or her
3 intermetamorphosis, in which the patient believes that people 
around have exchanged identities so that A becomes B, B becomes C, and so on
4 the syndrome of subjective doubles, where the patient is

4 the syndrome of subjective doubles, where the patient is 
convinced that exact doubles of him- or herself exist, a kind of Doppelgänger  phenomenonAdditional alternative forms have been described and sometimes 
features of more than one variant occur in an individual case, especially in the subjective doubles phenomenon.
Although the patient is convinced of the deception, he is often 
aware that something is wrong and that the replacements are subtly incorrect. Many sufferers are extremely distressed and frightened and fear impending harm. In some cases, they may become enraged and attack the ‘impostor’ with considerable violence. Their belief is of delusional intensity and they usually cannot be dissuaded by argument or by demonstration of contrary proof.
It is of particular interest that the misidentiﬁ  cation is not indis-

criminate but involves a limited number of usually familiar people. In some cases, substitution also involves places and objects. An admixture of depersonalization and derealization is not unusual, especially in the earlier stages.
(b) Classiﬁ  cation
Delusional misidentiﬁ  cation syndromes have not been included 
in DSM-IV or ICD-10, though if misidentiﬁ  cation occurs in the 
setting of a psychotic illness like schizophrenia it is regarded as a feature of that illness. However, if it is the principal aspect of a psychosis it should be regarded as a disorder sui generis . In those

cases where there is a discrete delusional system occurring in clear consciousness and within a relatively intact personality, it would seem logical to assign it as a new subcategory within Delusional Disorder (DSM-IV) or Persistent Delusional Disorders (ICD-10). In cases where organic brain disease is prominent, the proper assignment would be to Mental Disorders due to a General Medical Condition (DSM-IV) or Organic, Including Symptomatic, Mental Disorders (ICD-10).
(c) Diagnosis and differential diagnosis
The diagnosis is based on recognition of the delusional nature of the belief, the accompanying agitation, and uncharacteristic behaviours, possibly including violent attacks on others. A full neurological investigation is mandatory.
Differential diagnosis includes:
X Schizophrenia
X delusional disorder, persecutory subtype
X major mood disorder with delusions
X organic brain disorder
X substance abuse disorders.
(d) Epidemiology

The frequency of DMIS is unknown but an increasing number of cases are being reported. The disorder occurs in both sexes and across a wide age range, but particularly in the middle-aged and elderly.
(e) Aetiology
When DMIS was ﬁ  rst recognized, attempts were made to explain 
its symptoms on psychodynamic grounds. Such theories have been almost totally undermined of late by the increasing recognition of signiﬁ  cant brain pathology in a high proportion of cases.
Nowadays we have many reports on brain dysfunction in 
DMIS
(18,54,55) but large case series are lacking. There is some con-
sensus that abnormalities of the right cerebral hemisphere, espe-cially temporoparietal, are especially likely to be present but are not 4.4 persistent delusional symptoms and disorders

SECTION 4  clinical syndromes of adult psychiatry 624
inevitable, and lesions in other cerebral locations have been found. 
The lesions can be regarded as causal of speciﬁ  c abnormalities 
of face recognition, a function mediated especially in the right hemisphere. Also, there appears to be dissociation of sensory information from its normal affective accompaniment and failure of suppression of inappropriately repetitive behaviours (also a right-sided function). These last two features are very typical of delusional disorders in general.
We know little of the biological substrate of delusional symp-

toms, but one proposal is that there may be a dysfunction of the limbic–basal ganglia mechanisms, with particular emphasis on dopamine overactivity. In DMIS there seems to be a breakdown in integration of information between the right parietotemporal cortex, the limbic system, and certain basal ganglia, resulting in the specific misidentification, associated with inappropriate emotion and inability to suppress abnormal thoughts and behav-iours. Very tentatively it is possible to postulate a complex brain mechanism which normally integrates sensory and affective impulses and downregulates repetitive behaviour, and whose malfunction results in delusional beliefs, altered judgement, overintense mood, and inability to change or develop insight. The particular delusional content might be determined by the 
speciﬁ  c site within the mechanism at which the brain dysfunc-
tion occurred.
(56)

(56)
Although the above is simply an attempt at a paradigm, it is also 
a model with potential for the study of delusional and concomitant phenomena by modern neurobiological investigative methods. It also allows us to conjecture about the general similarities and speciﬁ  c differences between DMIS and delusional disorder.
(f) Course and prognosis
Although DMIS may appear insidiously, it not infrequently appears 
relatively suddenly in a previously normal individual, presumably related to the underlying cerebral pathology. Where brain damage is substantial, the prognosis is that of the brain disease. If the brain dysfunction is more subtle and does not remit, the delusional symptoms may become chronic. Forensic complications may occur if the patient becomes violent,
(47) and a small number of murders 
by patients have been reported in DMIS.
(g) Treatment

Acute treatment may involve sedation and antipsychoticmedication. Ongoing treatment is by maintenance doses of
an antipsychotic with possible addition of an anticonvulsant. Psychological counselling may be beneficial as the patient improves.
Folie à deux : a phenomenon which may 
accompany illnesses with delusions(57,58)
This phenomenon is listed as a psychiatric disorder in DSM-IV 
(Shared Psychotic Disorder, 297.3) and in ICD-10 (Induced Delusional Disorder, F24) but there is a conceptual difﬁ  culty in 
regarding it as a psychotic illness in its own right, as will be dis-cussed shortly.
Folie à deux  is a venerable term used to describe a situation in

Folie à deux  is a venerable term used to describe a situation in 
which mental symptoms, usually but not invariably delusions, are communicated from a psychiatrically ill individual (the‘primary patient’) to another individual (the ‘secondary patient’) who accepts them as truth. As noted, DSM-IV and ICD-10 refer 
to this by different names and there have been several confusing changes of ofﬁ  cial terminology over the years. The older name, 
which is used as an alternative by DSM-IV , is well known to most psychiatrists and is used here by preference. However, à deux
may sometimes be a misnomer since several people can be involved, and then we read of folie à trois ,folie à plusieurs ,folie à 
ménage , etc.
Taking the dyad as the classical situation, the two people are

Taking the dyad as the classical situation, the two people are 
usually closely associated, especially husband–wife, siblings, or parent–child, and often live in social isolation. The content of the shared belief depends on the predominant delusion(s) of the primary patient and can include convictions of persecution, delusional parasitosis, belief in having a child who does not exist, misidentiﬁ  cation delusions, and many others. There have been 
descriptions of shared persecutory and apocalyptic beliefs in quasi-religions and cults led by a charismatic leader with gullible followers. In many shared delusional examples there is a sense of antagonism from ‘them’ who may be deﬁ  ned or who may be what 
Cameron
(59) referred to as the ‘paranoid pseudocommunity’ , the 
hovering ‘they’ who carry out oppression which is evident to the sufferers but not to normal others.
Once thought rare, folie à deux  has been increasingly described

Once thought rare, folie à deux  has been increasingly described 
in the literature. Milder cases may not be recognized and, also, many delusional people strive to avoid psychiatric referral; collusion between primary and secondary patient in this has been noted. The physician should be aware of folie à deux  and never 
overlook it.
 ‘Shared psychotic’ and ‘induced delusional’ both imply that two 
members of the dyad are psychotic. In delusional disorder the primary patient is psychotic but the recipient of the beliefs usually is not. Most often, the latter is highly impressionable and depen-dent and adopts the false beliefs because of their intense and 
unceasing transmission by the primary patient. Social isolation,

unceasing transmission by the primary patient. Social isolation, 
accentuated by induced mistrust of ‘them’ , discourages adequate reality testing. Thus one can say that the content of the secondary patient’s false belief derives from psychotic thinking, but he or she is not usually psychotic.
Nearly all cases of folie à deux  are reported in association with 
schizophrenia, delusional disorder, severe depressive disorder with delusions, or early dementia, but it is probable that the condition also sometimes coexists with non-psychotic illnesses such as obsessive-compulsive disorder, somatoform disorder, and histrio nic–
dissociative personality disorder, in which the beliefs are intensely held and communicated but are not delusional. This makes the DSM-IV and ICD-10 terms even less appropriate.
Subtypes
In practice, the great majority of cases are of the type described, sometimes known as folie imposée  because the belief is impressed 
on the secondary patient.

Subtypes
However, one occasionally sees an alternative presentation, the 
so-called folie simultanée , in which two predisposed people develop 
illnesses with delusions and through long and over-close associa-tion come to share identical false beliefs. This is said to be likelier when there is a genetic link (for example two unmarried siblings) or when older people have lived together in considerable isolation for many years.

625
Folie à deux  is included with schizophrenia and other psychotic 
disorders in DSM-IV and with schizophrenia, schizotypal, and delusional disorders in ICD-10, and is regarded as a separate psy-chotic illness. It would be better to treat it as an important clinical phenomenon, which may be associated with other identiﬁ  able 
mental disorders. However, rather than encourage pedantic argu-ment, it is best to alert the clinician to its existence, its frequency, and, as will be seen, its importance.
Diagnosis
The phenomenon is recognized by the identical nature of the two individuals’ false beliefs, their gross affective investment in these, and their refusal to accept alternatives even when overwhelming proof is presented. Careful history-taking will usually readily dis-tinguish the primary from the secondary patient, but this can some-times prove difﬁ  cult. In the much less common folie simultanée , the 
distinction is largely irrelevant.

This is unknown except that, by deﬁ  nition, it will occur most in 
association with an illness characterized by delusional beliefs or severely overvalued ideas, especially under isolated conditions, and it is by no means rare. It is extremely important for the clinician to be on the lookout for it. He or she may be convinced that a patient is expressing delusional ideas but be thoroughly perplexed when an apparently rational relative unswervingly supports these. This can lead to serious mismanagement of the case. Conversely, recog-nition of folie à deux  may solve a bafﬂ  ing diagnostic problem and 
result in appropriate care for both individuals.
Aetiology
Folie à deux  appears to arise from a combination of the following:
1 innate impressionability and marked dependence on the primary 
patient
2 personality traits such as suggestibility, low initiative, poor reality 
testing, etc. in the secondary patient

patient
3 in some cases, low intelligence in the secondary patient
4 the intensity of the abnormal beliefs expressed by the primary 
patient
5 the length of time over which the abnormal beliefs have been 
imposed
6 the degree of social isolation
Treatment
In folie imposée  the logical approach is to identify the primary

patient
imposed
Treatment
In folie imposée  the logical approach is to identify the primary 
patient and treat his or her mental disorder adequately. It may also be helpful to separate the two individuals for a time, for example by hospitalizing the primary patient. With both people, every attempt must be made to reduce social isolation and to reintroduce them to reality. If the primary patient’s delusions improve with treatment, the secondary patient’s beliefs usually also improve. It is rarely appropriate to treat the secondary patient with antipsychotic medi-cation, although this is sometimes mistakenly done.
In folie simultanée , both patients require neuroleptic treatment.Theoretically, treatment is straightforward but in practice it can

In folie simultanée , both patients require neuroleptic treatment.Theoretically, treatment is straightforward but in practice it can 
be problematic. For example, the primary patient with delusional disorder often resists psychiatric help, and subterfuge and resis-tance by both individuals is common. In group situations, for example a cult, this resistance is likely to be widespread and intense, and will be justiﬁ  ed by the participants in terms of religious, social 
and legal rights, which they claim are being suppressed. The propa-gators should be separated from the recipients as much as possible, 
and the treatment team has to expend much time and diplomacy in 
gaining some conﬁ  dence and a degree of cooperation. Direct 
challenge of the beliefs in any shared delusional situation is usually totally counterproductive.
Mass suicide is a reported outcome of shared delusions in some 
cult situations and any danger of this must be countered with great urgency.
(60)

(60)
Treatment of delusional disorder
There are special aspects to the treatment of delusional disorder, which need emphasis, especially since many clinicians are unfamil-iar with them. The ﬁ  rst is that we must realize that delusional dis-
order is indeed treatable, despite frequent pessimistic statements to the contrary. In fact, the greatest difﬁ  culty is not treatment respon-
siveness, but persuading the patient that he needs psychiatric help because his delusions militate against this. With careful diagnosis and an approach that encourages the patient to cooperate, delu-sional disorder can respond to treatment, which in all cases will primarily be by neuroleptics.
General aspects of the treatment of delusions(61)

We usually aim to treat the illness of which the delusion is a part, but there is good evidence that delusions themselves, as well as hallucinations, can be considerably modiﬁ  ed by a psychological 
approach. In severe psychotic illnesses the initiation of psychologi-cal treatment usually has to follow the initial controlling of serious symptoms with medications or, on occasion, electroconvulsive therapy. Thereafter, a cognitive behavioural approach or, to a much lesser extent, conventional psychotherapy can help the individual to reduce preoccupation with false beliefs, become less isolated, and reorientate towards reality.
(62,63) But there is no good evidence 
that psychological methods by themselves can completely eliminate established delusions.
Since many illnesses are associated with delusions we have to

Since many illnesses are associated with delusions we have to 
tailor the psychopharmacological approach to suit each particular condition. In delusional disorder, the schizophrenias, and schizoaf-fective disorder, neuroleptics are the mainstay, with antidepres-sants, mood stabilizers, and electroconvulsive therapy sometimes playing subsidiary roles.
The rate of symptom response to treatment in a psychotic 
disorder is not uniform. For example, hallucinations often resolve quite quickly, but delusions can be much more persistent. Despite vigorous treatment they can last for many months and, in some patients, never fully remit. If the patient continues to be deluded, 
non-compliance with treatment is likely to be present, especially in

non-compliance with treatment is likely to be present, especially in 
delusional disorder where the individual is often expert at conceal-ing his or her lack of cooperation. At present it appears that all the subtypes of delusional disorder are potentially responsive to treat-ment. If treatment fails, always consider non-compliance before abandoning the current approach.4.4 persistent delusional symptoms and disorders

SECTION 4  clinical syndromes of adult psychiatry 626
Treatment approaches
Since so many delusional disorder patients actively resist seeing a 
psychiatrist, it is best to see them in a non-psychiatric setting if possible, for example in the ofﬁ  ce of the referring specialist or 
family physician. The psychiatrist who treats cases of delusional disorder needs much patience and tact, and it is common to spend one or more sessions ﬁ  rst gaining the individual’s conﬁ  dence 
and ﬁ  nally persuading him to give a psychotropic medication a 
trial. Many of them argue vehemently and with well-organized 
pseudologic against the premise that they are mentally ill and 
use all kinds of sophistry to deny the need for a neuroleptic, but a calm and persistent approach will gain cooperation in a good proportion of cases.
Whatever neuroleptic is prescribed it is essential to begin with

Whatever neuroleptic is prescribed it is essential to begin with 
the lowest effective dose. This dose is only raised if required and then very gradually to avoid side effects which are guaranteed to prompt withdrawal from treatment. The patient should be seen at least once a week as an outpatient in the initial stages. Inpatient treatment is not often indicated, although forensic cases will nearly always be seen in an institutional setting.
With a positive treatment response it is not unusual to see minor 
improvements in a few days, such as reduced agitation, a slight increase in well-being, improved sleep, and a little less preoccupa-tion with the delusion. On average it is about 2 weeks before the delusional system is signiﬁ  cantly ameliorated, but in some patients 
this may take 6 weeks or more.
Quite often if this degree of improvement occurs the patient

Quite often if this degree of improvement occurs the patient 
decides that there is no further need of treatment and stops it. Within days or weeks there is an inevitable return of the delusion with its accompanying agitation and preoccupation. It is then that the psychiatrist must be available to encourage resumption of medication. Although at this stage the patient still believes in his delusions, the experience of improvement followed by relapse makes a deep impression and, given trust in the therapist, often leads to long-term cooperation.
It is striking that good recovery is often relatively rapid and can 
be surprisingly complete, even when the illness has been present for many years. Some patients return to a considerable degree of

be surprisingly complete, even when the illness has been present for many years. Some patients return to a considerable degree of 
intrapsychic, interpersonal, and occupational functioning, with little evidence of the personality disorder that is supposed to be so prevalent in delusional disorder. Also, many patients require surprisingly little counselling or psychotherapy in resuming a rea-sonable life, although these should always be available if required. Such results suggest that this profound illness may be due to a rela-tively circumscribed brain abnormality and also that, in some cases at least, a very insidious onset may cause initial symptoms, which mimic personality disorder.
In most cases, treatment has to be continued for an indefinite

In most cases, treatment has to be continued for an indefinite 
period since delusional disorder is potentially a lifelongillness. Naturally the drug dosage should be the lowest, which keeps symptoms under control and this maintenance doseis often very low indeed. Perhaps up to one-third of patients can eventually be weaned successfully from medication, butwe have no means of predicting who these will be, so that any reduction in effective treatment must be carried out with extreme caution. Sadly, a proportion of relapses are due to inju-dicious withdrawal of treatment by a physician and we must assume the need for treatment to be permanent unless proved otherwise. It is interesting that successfully treated patients, 
whether on maintenance drugs or not, keep a lookout forsubsequent recurrences themselves and may report thattension-inducing circumstances provoke some reappearance of symptoms. Such patients may then request to have their medi-cation resumed or increased.

There is no necessary correlation between acquired insight 
into the desirability of taking one’s medication and true insight into the illness itself. Many patients never fully accept the psychotic nature of their experience, but as long as they are beneﬁ  ting from 
treatment and are functioning reasonably there is nothing to be 
gained from challenging them on this. If, despite treatment, the delusions remain intrusive, cognitive behavioural therapy and counselling should be available,
(62,63) but intrusive psychotherapy 
must be avoided.
Overall, the best-attested treatment results refer to the somatic 
subtype, with smaller literatures on the erotomanic, jealousy,and persecutory subtypes, and virtually nothing on the grandiose form. A wide variety of neuroleptics have been reported, but for a considerable time pimozide, a diphenylbutylpiperidine, was the drug of ﬁ  rst choice.
(64) Recently a study by Manschrek and col-

leagues(65) has apparently shown that some of the newer atypical 
antipsychotics can produce comparable results. Antidepressants and benzodiazepines are ineffective as ﬁ  rst-line treatments and 
monoamine oxidase inhibitor antidepressants are absolutelycontraindicated.
Currently, the best estimate of treatment outcomes is that, if the 
diagnosis is correct, the patient compliant, and the treatment adequate, recovery (deﬁ  ned as ‘return to full function with total or 
near-remission of symptoms’) occurs in approximately 50 per cent of all patients, and a further 30 per cent will show signiﬁ  cant but 
less complete improvement. An unknown, but considerable, pro-portion of those who show no improvement can be assumed to have been non-compliant. Although mostly based on non-blind trials, these ﬁ  gures are culled from a worldwide literature, which 
does show considerable consistency.
Recognition and treatment of postpsychotic 
depression

T en per cent or more of delusional disorder patients whose illness 
responds to neuroleptics experience signiﬁ  cant degrees of mood 
disorder during recovery, sometimes very severe depression with suicidal risks.
(66) This has also been noted in recovering 
schizophrenics. Various explanations have been proposed such as a medication side effect or perhaps the achievement of painful insight. The most likely reason is neurochemical, due to rapid changes in neurotransmitter balance.
If the neuroleptic is withdrawn, the depression tends to improve

If the neuroleptic is withdrawn, the depression tends to improve 
but the delusions return. Therefore the proper approach is to continue with the minimum effective dose of neuroleptic and to add an antidepressant drug in an effective dose. Occasionally, in extremely severe cases, electroconvulsive therapy is required. Subsequently the neuroleptic is continued but, in most instances, the antidepressant can be gradually reduced.
All cases of delusional disorder should be monitored for the 
possible emergence of mood symptoms during recovery and treat-ment immediately instituted if necessary. If suicidal symptoms 
appear, inpatient admission is highly recommended.

627
Paranoia/delusional disorder is unique in psychiatry in that it is 
virtually a newly discovered illness, yet much of the fundamental descriptive work was done a century or more ago. This long hiatus means that most practitioners have little knowledge or experience of the disorder, and the few who are aware of it usually only see a small part of the fabric. The dermatologist treats a case of delu-sional parasitosis, the cosmetic surgeon has an impossible patient wth a dysmorphic delusion, the lawyer does not know what to do with a totally unreasonable litigant, the police ofﬁ  cer has to 
deal with a jealous murderer or an erotomanic stalker, and thepersonnel ofﬁ  cer has an employee who is convinced his fellow 
workers are persecuting him, etc. How can we draw all this scat-tered material together and add it to the psychiatric literature to 
make a whole c loth? The answer is largely by consciousness raising 
and education.

Kendler, an authority in this ﬁ  eld, has said, ‘The paranoid dis-
orders may be the third great group of functional psychoses, along with affective disorder and schizophrenia’ .
(67) If he is cor-
rect, it is imperative that we hone our diagnostic and treatment skills in order to improve the help we might offer to delusional disorder sufferers and to facilitate research which is so badly needed.
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4.5
4.5.1 Introduction to 
mood disorders
Mood and disorders of mood
The concept of mood is difﬁ  cult to deﬁ  ne. In psychiatry, it has come 
to mean a pervasive emotional tone varying along an axis from hap-piness to sadness—and perhaps anxiety. The boundaries between normal and abnormal mood are equally difficult to define. Nonetheless, there is usually no doubt about the most extreme man-
ifestations of low mood, depression , or elevated mood, mania .
Early history
Descriptions of variations in mood which go beyond normal limits 
and are associated with functional impairment are present in the oldest writings of mankind.
(1) The ancient Greeks identiﬁ  ed that 
mood disorders were diseases of the body, rather than the effects of supernatural spirits and identiﬁ  ed the link between elevation of 
mood and states of despondency or depression. The Hippocratics also identiﬁ  ed that mental disorders were located in the brain. This

mood and states of despondency or depression. The Hippocratics also identiﬁ  ed that mental disorders were located in the brain. This 
insight was lost for 2000 years under the inﬂ  uence of Galen’s 
humoral theory which held that melancholia was due to an excess of black bile and mania due to an excess of yellow bile. During this period, attempts to put forward empirical theories in both Western and Eastern civilizations often fell foul of increasingly dominant religious dogma.
Development of modern psychiatric 
nosology
In Europe, during the Enlightenment of the seventeenth and eigh-
teenth centuries, reason and empiricism once again emerged. In Anatomy of Melancholy , published in 1632, Richard Burton provides 
a comprehensive review of previous writings on mood disorder.
(2)

(2)
Burton, who writes with the penetrating insight of someone with extensive personal experience of mood disorder, clearly makes the link between mood elevation and enhanced creativity, cycling with periods of low mood, when all pleasure is lost:
When I go musing all alone
Thinking of divers things fore-known.
When I build castles in the air,
Void of sorrow and void of fear,Pleasing myself with phantasms sweet,
Methinks the time runs very ﬂ  eet.
All my joys to this are folly,Naught so sweet as melancholy.When I lie waking all alone,Contents
  4.5.1 Introduction to mood disorders
disorders and mania
Per Bech
  4.5.3 Diagnosis, classiﬁ  cation, and differential diagnosis of the mood disorders
  4.5.4 Epidemiology of mood disorders

Per Bech
 4.5.5 Genetic aetiology of mood disorders
 4.5.6 Neurobiological aetiology of mood disorders
  4.5.7 Course and prognosis of mood disorders
  4.5.8 Treatment of mood disorders
  4.5.9 Dysthymia, cyclothymia, and hyperthymia

SECTION 4  clinical syndromes of adult psychiatry 630
Recounting what I have ill done,
My thoughts on me then tyrannise,
Fear and sorrow me surprise,
Whether I tarry still or go,Methinks the time moves very slow.
All my griefs to this are jolly,
Naught so mad as melancholy.
(extract from The Author’s Abstract of Melancholy, Anatomy of 
Melancholy )
Burton’s work is an erudite and comprehensive review of the work 
on mood disorders until the early seventeenth century, although of course not systematic in the modern sense. Following Burton, Thomas Willis (1621–1675), Sedleian Professor of Natural Philosophy at Oxford University, perhaps better known for his description of the eponymous circle of Willis, is now recognized as one of the ﬁ  rst to 
(re)localize psychiatric disorders within speciﬁ  c body organs, pri-
marily the brain, rather than due to the circulation of bodily humours. In Cerebri anatomi  (1664) Willis writes
(3):

(3):
Melancholy is a complicated distemper of the brain and heart. For as 
melancholick people talk idly, it proceeds from the vice or fault of the brain and the inordination of the animal spirits dwelling in it, but as they become very sad and fearful, this is deservedly attributed to the passion of the heart. But we cannot here yield to what some physicians afﬁ  rm, that melancholy doth arise from a melancholick 
humour. Melancholy being a long time protracted, passes oftentimes into stupidity, or foolishness, and sometimes into madness .
This identiﬁ  cation of the physical brain as the location of the 
involved pathological processes initiated the modernist project of the scientiﬁ  c study of serious mood disorder, using contemporarily

involved pathological processes initiated the modernist project of the scientiﬁ  c study of serious mood disorder, using contemporarily 
available scientific methods to generate insights into diagnosis, aetiology, course, and treatment. The ﬁ  rst steps in this project were 
diagnosis and classiﬁ  cation. Modern psychiatric diagnostic systems 
can be traced to post-Enlightenment Europe—in particular, France. The development of the mental hospital system throughout Europe provided the populations of patients for the early psychiatriststo study, as they created and reﬁ  ned diagnostic systems. In 1854, 
Esquirol described la folie circulaire which remains a recognizably 
modern description of bipolar disorder.
(4) Despite this, the prevalent 
view throughout the nineteenth century was that manic and depressive states were separate entities. At the turn of the twentieth century, Kraepelin distinguished dementia praecox  from manic-depressive 
insanity

insanity
(5) Kraepelin emphasized the episodic course of the latter,
the relatively benign prognosis and the family history of mooddisorder.
Expanding the scope of mood disorder and 
recognition of diagnostic heterogeneity
In the twentieth century, diagnostic systems that had derived from 
the populations of large mental hospitals were challenged by the rec-ognition that mental disorders were widespread in milder forms in the general population. Under the influence of Freud, Bleuler expanded Kraepelin’s original concept of dementia praecox to include some of the less severe forms that he identiﬁ  ed in the general 
population and renamed the disorder schizophrenia  to reﬂ  ect his 
views of the fundamental psychology of the psychosis.
(6) A similar

(6) A similar 
process to this occurred with the mood disorders, eventually leading to the recognition that milder, albeit still severe enough to cause impairment of function, forms of depression, and anxiety were the commonest forms of mental disorder in the general population. Indeed, after the World Health Organization and World Bank’s Global Burden of Disease study in the 1990s, it became clear that unipolar depression was the among the most important causes of disability worldwide.
(7) With the expansion in the scope of mood

(7) With the expansion in the scope of mood 
disorders, it was recognized that there is also heterogeneity in the way in which mood disorders manifest themselves. There was debate about existence of subtypes of depression, often based on the severity of symptoms and hypothesized links to an underlying brain process. For example, Gillespie’s reactive depression in which the depressive 
disorder develops in response to external circumstances and remains subject to inﬂ  uence by external inﬂ  uences during its course, can be 
contrasted with endogenous  and melancholic subtypes which were 
held to arise from a primary neurobiological abnormality.
Fig. 4.5.1.1 Frontispiece to Burton’s Anatomy of Melancholy.

631
The distinction between unipolar and 
bipolar disorders
Despite having some descriptive clinical utility, most postulated 
depressive subgroups have remained of uncertain status. The distinction between unipolar and bipolar disorders, however, has become accepted and is included in modern diagnostic systems. Initially, during the twentieth century, diagnostic systems con-tinued to maintain the Kraepelinian approach to mood disorder with manic-depressive insanity  including both severe mania 
and depression.—i.e. illnesses that were characterized only by depressive episodes and illnesses which included both poles.
The school of Kleist and Leonhard identiﬁ  ed the heterogeneous

The school of Kleist and Leonhard identiﬁ  ed the heterogeneous 
nature of patients with manic-depressive illness—some had both manic and depressive episodes while others had only depressions. They coined the terms bipolar and unipolar to describe these two forms. Carl Perris and Jules Angst later provided some empirical validation for the separation on the basis of family history.
(8,9)
Modern diagnostic systems—the birth of 
diagnostic criteria
Under the inﬂ  uence of psychoanalytic thought, psychiatric diagnoses
had become very vague and unreliable by the 1960s—particularly in the United States where psychoanalysis was particularly inﬂ  uen-

tial. Following the observation that schizophrenia was more pre-valent in the United States than in United Kingdom, the US–UK Diagnostic project showed conclusively that the apparent differences appeared to be due to the differences in diagnostic practice rather 
than true differences in prevalence.
(10) The US–UK Diagnostic 
project highlighted the unacceptable reliability of psychiatric diag-noses which fuelled the arguments of critics of psychiatry. It was recognized that more reliable diagnostic systems were required which were explicitly based on evidence of validity. The deﬁ  ning 
feature of these systems was the use of explicit diagnostic criteria and, historically, the most important of these was the third edition of the Diagnostic and Statistical Manual of the American Psychiatric Association.
(11)

(11)
International classiﬁ  cation systems were based on compromise 
between national views rather than evidence and were there-fore slower to change. The ninth edition of the World Health Organization’s International Classiﬁ  cation of diseases retained the 
concept ‘Manic-Depressive Illness’ which included both unipolar and bipolar disorders. However, the distinction was ﬁ  nally made in 
the 10th edition in 1993.
(12)
Reﬁ ning the concept—subgroups of 
unipolar and bipolar disorder
As well as the fundamental Kraepelinian distinction between mood 
disorders and schizophrenia and the subsequent distinction between unipolar and bipolar mood disorders, there have been several attempts to subclassify mood disorders.
Unipolar disorder
A crucial distinction has been made between endogenous and 
reactive forms of unipolar depressive disorder (see above). Current 
classiﬁ  cations do not emphasize the distinction because it is now

classiﬁ  cations do not emphasize the distinction because it is now 
recognized that both typical endogenous and reactive clinical pictures can be related to external stressors. Nonetheless, the con-cept of a melancholic subtype remains.
Bipolar disorder
As more is known about the epidemiology of bipolar disorder, it has become apparent that some people do not experience manic episodes, but nonetheless do experience episodes of mood elevation that are clearly noticeable to themselves and others (hypo mania)- as well as depressive episodes. T o accommodate these heterogeneous clinical pictures, bipolar disorder has been divided into bipolar disorder, type 1 (mania ± depression) and bipolar disorder, type 2 (hypomania +

depression). A focus of intense current research is the concept of bipolar spectrum disorder—in other words, the recognition that there is probably a continuum of mood phenomena from normal mood through to extreme mania.
Future developments in the classiﬁ  cation of 
We can expect more changes in the diagnostic classiﬁ  cation as 
knowledge continues to accrue. Our current classiﬁ  cations remain 
entirely descriptive, based on cross-sectional clinical symptoms and longitudinal course. As such, the classiﬁ  cations have been 
therapeutically useful—we now have increasing evidence for the diagnosis-specific effects of treatments. In the future, as out knowledge of the basic neurobiology of mood disorder increases, incremental or fundamental changes may be required.
Fig. 4.5.1.2 Illustration by Christopher Wren from Cerebi anatome  by Thomas W illis.4.5.1 introduction to mood disorders

SECTION 4  clinical syndromes of adult psychiatry 632
Goodwin, F.K. and Jamison, K.R. (2007). Manic-depressive illness: bipolar 
disorders and recurrent depression  (2nd revised edn). Oxford University 
Press, USA.
 1. Goodwin, F.K. and Jamison, K.R. (1990). Manic depressive illness .
 2. Burton, R (1632). Anatomy of Melancholy. http://onlinebooks.library.
upenn.edu/webbin/gutbook/lookup?num=10800
 3. Willis, T. (1664). Cerebri anatome: cui accessit nervorum descriptio 
et usus . J. Martyn & J. Allestry, London.
 4. Esquirol, J.E.D. (1838). Des maladies mentales . Balliere, Paris.
 5. Kraepelin, E. (1896). Lehrbuch der psychiatrie  (5th edn). Barth, Leipzig.
 6. Bleuler, E. (1950). Dementia praecox or the group of schizophrenias .
International Universities Press, New Y ork.
 7. Murray, C.J. and Lopez, A.D. (1997). Global mortality, disability, 
and the contribution of risk factors: global burden of disease study.

and the contribution of risk factors: global burden of disease study. 
Lancet ,349, 1436–42.
 8. Perris, C.A. (1966b). Study of bipolar (manic-depressive) and unipolar 
recurrent depressive psychoses I. Genetic investigation. Acta Psychiatrica Scandinavica ,42(Suppl. 194), 15–44.
 9. Angst, J. (1966). Zur Ätiologie und Nosologie endogener depressiver 
Psychosen . Springer, Berlin.
10. Cooper, J.E., Kendell, R.E., Gurland, B.J., et al. (1972). Psychiatric 
diagnoses in New York and London . Maudsley Monograph No. 20. 
Oxford University Press, London.
11. American Psychiatric Association. (1980). Diagnostic and statistical 
manual of mental disorders  (3rd edn DSM-III). APA, Washington, DC.
12. World Health Organization. (1992). The ICD-10 classiﬁ  cation of mental 
and behavioural disorders . World Health Organization, Geneva.
4.5.2 Clinical features of

4.5.2 Clinical features of 
mood disorders and mania
Per Bech
The clinical features of mood disorders are dimensional, i.e. dis-
tributed according to their severity.(1) The categorical approach as 
manifested in the DSM-IV or ICD-10 does not, however, preclude dimensional descriptions, because in DSM-IV as well as in ICD-10 the categories or diagnoses are essentially deﬁ  ned by minimum and 
maximum cut-off scores on the symptomatic states.
Fig. 4.5.2.1 shows a coordinate system in which the ordinate 
represents the dimension of manic states and the abscissa the dimension of depressive states. The cut-off scores refer to the standardization of the isometric rating scales for mania and depression.
(1–3) Jamison(4) has argued that the term ‘bipolar’ per-

petuates the notion that: ‘ . . . depression exists rather tidily segregated in its own pole, while mania clusters off neatly and discretely on another. This polarisation of two clinical states ﬂ  ies in the face of 
everything that we know about the ﬂ  uctuating nature of manic-
depressive illness . . . and it minimises the importance of mixed 
manic-depressive states’ . William James referred to the stream of consciousness to emphasize its continuity in contrast to its concep-
tion as a series of discrete states. However, William James actually confessed that during his own depressive episodes, his mood states,
(5)
to a large extent, blocked his own stream of consciousness.(6) In the 
perspective outlined by Jamison,(4) polarity in the clinical world is

(5)
perspective outlined by Jamison,(4) polarity in the clinical world is 
not two opposites that contradict each other by a logical rela tionship of juxtaposition. Polarity should rather, as shown in Figs. 4.5.2.1 and 4.5.2.2, be considered at a level of psychological intercorrelations in which clinical mania and depression exist by virtue of each other involving both negative and positive correlations.
The symptom rating scales shown in Fig. 4.5.2.1 measure the 
severity of mania, depression, or mixed states and have a time frame of 3 days. Clinically, this is the minimum for the measure-ment of the spectrum of mood states ranging from subthreshold states to states of psychotic severity.
Ultrashort states of mood swings are often seen without any ref-
erence to mood disorders. In one of Henry James’ masterpieces, The Ambassadors, his autobiographical hero has a tendency

erence to mood disorders. In one of Henry James’ masterpieces, The Ambassadors, his autobiographical hero has a tendency 
towards being introverted in the morning, while in the afternoon 
and evening he is more extraverted, like a man ‘ . . . who, elately ﬁ nding in his pocket more money than usual . . . ’ , though without 
spending a lot. This 24-h ‘cyclothymia’ between introversion and extraversion displays too mild a symptomatology to be part of a ‘bipolar’ disorder and might be referred to as a temperamental neuroticism. Thus, Eysenck’s original questionnaire for measuring neuroticism included items of being moody without any apparent reason or being inclined to having frequent ups and downs in mood.
(7) Neuroticism now seems to include subclinical, tempera-
mental, low, negative affectivity (worrying, gloomy, dysphoric, and hostile).
Fig. 4.5.2.2 shows another coordinate system in which the

Fig. 4.5.2.2 shows another coordinate system in which the 
ordinate is representing the dimension of mania severity and the abscissa the dimension of depression severity, but covering the life-long correlation of the courses of manic and depressive episodes, Fig. 4.5.2.1 Patient state ﬂ  uctuations within the spectrum of mood states 
from the subthreshold states over minor mood states (hypomania or minor depression) to major states (mania/psychotic mania or major depression without 
or with psychotic symptoms) and to the mixed states.Mania scale
scores
35
Psychotic mania
30
Severe mania
25Mixed states
Mania
20
Hypo mania
15
Subthreshold states
10
Partial
remission
5
Remis
-sion
Minor depression
Major (moderate)
Major (severe)
Major (psychotic)
depressionDepressionscale scores
51 0 1 5 2 0 2 5 3 0 3 5

633
i.e. the longitudinal diagnosis of mood polarity disorders. While a 
unipolar course of manic episodes without any depressive episodes is very rare,
(8) the course of unipolar depressive episodes without 
manic episodes is much more frequent. Angst(9) has criticized the 
DSM-IV deﬁ  nitions of depressive episode disorders (a duration of 
at least 2 weeks) and of manic episode disorder (a duration of at least 1 week). Thus, Angst has shown that these episode duration criteria are not only too narrow (not sensitive enough), but they also lack empirical evidence (not validated). The spectrum of mood polarity as shown in Fig. 4.5.2.2 is an attempt to refer to the DSM-IV deﬁ  nitions, though modiﬁ  ed with reference to Angst.
(9)
The mood polarity disorder as shown in Fig. 4.5.2.2 is deﬁ  ned by

(9)
The mood polarity disorder as shown in Fig. 4.5.2.2 is deﬁ  ned by 
the highest score a given patient has obtained in the coordinate system at any time. Unipolar depression, however, with a score of 10 or less on the mania scale, as shown in Fig. 4.5.2.2, remains a lifelong uncertain diagnosis. Thus, Angst
(9) has demonstrated a 
persistent risk of 1–2 per cent per year of a diagnostic change from unipolar to bipolar disorder.
The dimensional approach has been valid also in regard to per-
sonality disorder. As discussed by Angst,
(9) only around 15 per cent 
of the general population seem to report no lifelong personality disorders, and he therefore calls these persons ‘supernaturals’ . Thus, nearly everyone has some kind of personality disorder, and within the spectrum of mood personality disorders, extraversion, introversion, neuroticism, hyperthymia, dysthymia, and cyclothy-mia are to be considered subthreshold disorders as shown in Fig. 4.5.2.2.

It has recently been argued that when taking into account both 
the subthreshold levels of symptoms and the short states of 2–3 days’ duration rather than the whole DSM-IV episodes, there appears to be a linear correlation between mania and depression in the course of illness in many patients with mood disorders.
(10)The depressive episode: duration 
and severity
Table 4.5.2.1 shows the DSM-IV and ICD-10 depressive symptoms 
for the diagnosis of major depression, which to a large extent covers the rating scale dimension in Fig. 4.5.2.1. Thus, the individ-ual symptoms should be present most of the day and nearly every day during an episode. Kendler and Gardner
(11) have shown that 
the risk of developing a new major depressive episode (i.e. of a duration of 14 days or more) is as high for patients with major depressive symptoms lasting from 5 to 13 days as for patients with symptoms lasting from 14 to 59 days.
The study by Kendler and Gardner
(11) has also demonstrated

(11) has also demonstrated 
that patients with a subthreshold quantity of depressive symptoms (i.e. just below ﬁ  ve out of the nine DSM-IV symptoms listed 
in Table 4.5.2.1 or minor depression in Fig. 4.5.2.1) had the same risk of developing a new major depressive episode as patients fulﬁ lling the symptomatic criteria of major depression. It has been 
shown that approximately 50 per cent of the patients fulﬁ  lling 
the ICD-10 category of mild depression also fulﬁ  l the criteria for 
DSM-IV major depression.
T o illustrate how a major depressive episode often develops on a 
continuum of depressive symptoms from the ﬁ  rst prodromes of 
decreased positive well-being (introversion) to the major depres-
sive episode, a layman’s description is shown in Box 4.5.2.1. These 
autobiographical notes of the late William Styron (1925–2006) 
describe his ﬁ  rst episode of depression at the age of 60.
(12) As

(12) As 
indicated, the symptom of anxiety (not included in DSM-IV or ICD-10) is a very important symptom of major depression from its 
very onset. When suicidal impulses developed, he was admitted to Y ale New Hospital.Fig. 4.5.2.2 Patient state lifetime ﬂ  uctuations within the spectrum of mood 
polarity syndromes or disorders from the temperamental neuroticism over minor disorders (dysthymia or cyclothymia) to major unipolar disorders (hypomania/ mania or brief/major depression) and to the various bipolar disorders.Mania scale
scores
35
30
Bipolar I
25Unipolar mania
•  recurrent
    mania•  recurrent
   hypomania20
Bipolar II-IV
15
Cyclothymia
10
Unipolar depression
•  recurrent major depression
•  recurrent brief depressionExtra-
versionNeuro-
ticism
5
Intro-
versionDepression
scale scores
5 1 0 1 52 02 53 03 5Hyper-
thymia
Dys-
thymia

10
ticism
5
Intro-
thymia
Dys-
thymia
Table 4.5.2.1  Depression symptoms as included in DSM-IV and 
ICD-10
Symptoms of depression DSM-IV ICD-10
 1 Depressed mood most of the day, nearly every day + +
 2 Markedly diminished interest or pleasure in all, or 
almost all, activities most of the day, nearly every day++
 3 Loss of energy or fatigue nearly every day + +
 4 Loss of conﬁ  dence or self-esteem – + 5 Unreasonable feelings of self-reproach or excessive or 
inappropriate guilt, nearly every day++
 6 Recurrent thoughts of death or suicide, or any 
suicidal behaviour++
 7 Diminished ability to think or concentrate, or 
indecisiveness, nearly every day++
 8 Psychomotor agitation or retardation nearly every day + +
 9 Insomnia or hypersomnia nearly every day + +10 Change in appetite (decrease or increase with

 9 Insomnia or hypersomnia nearly every day + +10 Change in appetite (decrease or increase with 
corresponding weight change)++
+ indicates that the symptom is included; − indicates that the symptom is not included.4.5.2 clinical features of mood disorders and mania

SECTION 4  clinical syndromes of adult psychiatry 634
Major depression with or without melancholia
Negative beliefs such as ‘loss of self-esteem’ or ‘inappropriate guilt’ 
are among the most speciﬁ  c core symptoms of major depression. 
Inappropriate guilt can be experienced as a punishment for past misdeeds (prior to the current episode of depression). The prevail-ing element of negative beliefs is a sense of loss which is associated with lower self-esteem experienced retrospectively. The symptom which discriminates best between anxiety states and major depres-sive disorder is guilt.
However, also states of anxiety with worrying and panic are 
important symptoms of depression. Anxiety is among the core items of the Hamilton Depression Scale.
(13) Patients suffering from

(13) Patients suffering from 
subthreshold depression experience less anxiety than patients with major depression. Another important symptom of depression included in the depression dimension of Fig. 4.5.2.1, but not in Table 4.5.2.1, is emotional and social withdrawal. Within the ﬂ  ux 
between mania and depression, this is probably another speciﬁ  c 
symptom (the emotionally intrusive behaviour in mania is its opposite pole).
Both in DSM-IV and ICD-10, major depressive states can be 
further speciﬁ  ed as melancholic or somatic syndromes. In earlier 
descriptions (including Freud’s ‘Mourning and melancholia’), endogenous or somatic depression is distinguished from psychoge nic 
or reactive depression by ‘early morning awakening’ and ‘depres-sion regularly worse in the morning’ . These two signs are the

or reactive depression by ‘early morning awakening’ and ‘depres-sion regularly worse in the morning’ . These two signs are the 
only features of somatic or melancholic depression not included in the list of symptoms in Table 4.5.2.1. Strictly speaking, diurnal variation of symptoms is not a symptom itself, but rather a descrip-tion of the ﬂ  uctuation. The most ‘somatic’ symptom in Table 4.5.2.1 
is change in body weight (Styron had lost 20 to 25 pounds over a period of 6 weeks, when the illness developed into a major depression).
(14)
Styron’s depression (Box 4.5.2.1) included the somatic feature 
of early morning awakening and suicidal thoughts. The latter are not just a consequence of the other symptoms. Styron described how during depression he could still keep ‘ …the idea of suicide at 
bay…’ . At a later stage (not shown in Box 4.5.2.1), just before he

bay…’ . At a later stage (not shown in Box 4.5.2.1), just before he 
was admitted to hospital, Styron tried to write a suicide letter. Suicidal thoughts were often present late at night, when anxiety symptoms had lifted.
Measurements of social behaviour and subjective distress have 
shown that acute major depression is one of the most disabling and distressing of medical disorders.
(6) The constant mental pain and

(6) The constant mental pain and 
the suicidal symptoms seriously affect quality of life. The suicidal risk in major depression is especially high when psychomotor retardation is improving in the course of treatment. The treating physician or the relatives typically observe improvement in the depressive symptoms before the patient does, because psychomotor retardation improves before mood state or hopelessness do. The risk is especially high in socially isolated people. Major depression has the highest risk of suicide of all mental disorders, and all patients with major depression should be assessed for the risk of suicide. It has been shown that patients with unipolar depression have higher suicide rates than patients with bipolar I and bipolar II disorders. However, concerning the core items of severe depressive

states, no differences in the intensity of symptoms have been seen between unipolar and bipolar patients.
Major depression with psychotic features
According to DSM-IV or ICD-10, the term ‘psychotic depression’ 
is not synonymous with endogenous or melancholic depression. This agrees with Hamilton
(13) who used the term ‘psychosis’ 
to refer to the severity of symptoms. As stated by Hamilton:(13) ‘ . . . 
a schizophrenic patient, who has delusions is not necessarily worse than one who has not, but a depressive patient who has is much worse . . . ’ .
Recurrent depression
Recurrent major depression
After a single episode of major depression, around 85 per cent of patients experience recurrent episodes. While the ﬁ  rst episode of

After a single episode of major depression, around 85 per cent of patients experience recurrent episodes. While the ﬁ  rst episode of 
major depression is often provoked by a negative life event such as loss of job, retirement, marital separation or divorce, subsequent episodes are often unprecipitated (but positive life events can also provoke depression). Depressive episodes typically increase in frequency and duration as they return.
(3)
Recurrent brief depression
The symptoms of recurrent brief depression, ﬁ  rst described by 
Angst, are similar to those of major depression (Table 4.5.2.1) with regard to both number and severity. Recurrent brief depression is a Box 4.5.2.1  The stages from decreased positive well-being 
through mild depression to major depression without psychotic features
XThe shadows of nightfall seemed more sober, my mornings

XThe shadows of nightfall seemed more sober, my mornings 
were less buoyant, walks in the woods became less zestful, and there was a moment during my working hours when a kind of panic and anxiety overtook me, just for a few minutes, accompanied by a visceral queasiness . . . 
X. . . As the disorder gradually took full passion of my system, I began to conceive that my mind itself was like one of those outmoded small-town telephone exchanges, being gradually inundated by ﬂ  ood-waters.
X. . . I particularly remember the lamentable near disappearance 
of my voice . . . The libido also made an early exit . . . food, like everything else within the scope of sensation, was utterly without savor.

X. . . My few hours of sleep were usually terminated at three or four in the morning, when I started up into yawning darkness . . . I’m fairly certain that it was during one of these insomnia trances that there came over me the knowledge that this condition would cost me my life, if it continued on such a course . . . I had not conceived precisely how my end would come. In short, I was still keeping the idea of suicide at bay . . . What I had begun to discover is that the grey drizzle of horror, induced by depression, takes on the quality of physical pain . . . 
(from W. Styron (1990), Darkness visible. A memoir of madness ,
Random House, New Y ork.)

635
state of major depression lasting 2–3 days. Its diagnosis has not 
been adopted fully in DSM-IV , but it is included in ICD-10. It should be distinguished from recurrent suicidal behaviour, for example in patients with borderline personality disorder.
Seasonal depression
Seasonal depression is seen most frequently in winter, and less frequently in summer. In DSM-IV , seasonal depression has been adopted as a speciﬁ  er (rather than a diagnostic category) which 
can be applied not only to recurrent depression but also to bipolar disorder. The seasonal episodes (e.g. winter depression) have to outnumber any non-seasonal depressive episodes in the same patient. In ICD-10 only seasonal depression is brieﬂ  y mentioned, 
but only in an annex for disorders under consideration.
According to DSM-IV , the symptoms of seasonal depression are

According to DSM-IV , the symptoms of seasonal depression are 
similar to those of major depression. However, it has been shown that the symptoms differ from those of major depression, with hypersomnia, overeating, carbohydrate craving, and weight gain (often referred to as atypical depression).
Atypical depression
DSM-IV atypical depression has a speciﬁ  er which can be applied 
both to major depression and to bipolar I and bipolar II, but also to dysthymia. The core item is mood reactivity (i.e. the mood brightens in response to actual or potential positive events), while the associated symptoms are hypersomnia, overeating, and weight gain, leaden feelings in arms or legs, and interpersonal rejection sensitivity. It has been shown that mood reactivity is more often seen in bipolar II disorders than in unipolar depression disorders.
The manic episode: duration and severity

Table 4.5.2.2 shows the symptoms of mania according to DSM-IV and ICD-10, which to a large extent covers the rating scale dimen-sion in Fig. 4.5.2.1. The episode criteria for hypomania and mania are shorter than those for major depression. For hypomania, the symptoms should have lasted at least 4 days, and it has beensuggested to accept as little as 2 days (e.g. for states of hypoma-
nia).
(15) In DSM-IV , but not in ICD-10, the category bipolar II dis-
order has been adopted (Fig. 4.5.2.2), referring to patients with a major depressive episode, who previously have experienced epi-sodes of hypomania. It has been shown that patients with cyclothy-mia have the same risk of developing bipolar II depression as 
patients with hypomania. It has been proposed to extend the bipo-lar spectrum to include a category of bipolar III to refer to depressed 
patients who have developed hypomania episodes during treat-ment with antidepressant medication,

(16) while bipolar IV refers to 
depressed patients having a substance-induced hypomania.
Patient-reported questionnaires have recently been published 
to identify previous episodes of hypomania in depressed patients. It has been shown that the Hypomania Checklist
(17) is superior to 
the Mood Disorder Questionnaire in identifying patients with bipolar II disorder.
The problem with self-reported questionnaires to measure manic 
symptoms is that many patients do not perceive their hypomanic symptoms as pathological. They may describe themselves as ‘normal’ or their response pattern may show that they play ‘the manic game’ .
Studies with clinician-rated mania scales have shown that the

Studies with clinician-rated mania scales have shown that the 
various symptoms in Table 4.5.2.2, when quantified, can be rank-ordered in one single dimension of severity, analogously to the depressive symptoms in Table 4.5.2.1. This is illustrated by Box 4.5.2.2, which lists the three stages of mania from the longitu-dinal study by Carlson and Goodwin
(18) on hospitalized patients in 
the untreated stage of their illness.
Hypomania
Hypomania can be the ﬁ  rst stage of a spiralling upswing of mood 
(Box 4.5.2.2). According to DSM-IV , hypomania is more in concor-dance with the following description by Jamison
(4) than with

(4) than with 
Box 4.5.2.2: ‘ . . . When you’re high it’s tremendous. The ideas and feelings are fast and frequent . . . Shyness goes, the right words and gestures are suddenly there, the power to captivate others a felt certainty . . . Sensuality is pervasive and the desire to seduce and be seduced irresistible’ . The shyness or introversion seen in mild depression or dysthymia contrast with the lack of shyness and extraversion seen in the hypomanic patient.
As described in Box 4.5.2.2, the dysphoric or irritable mood 
is often a core symptom of hypomania, which in the next stage of mania develops further, to cooperation difﬁ  culties and impul-
sive hostility. Although hypomania might cause hyperactiveness in social functioning,
(15) the more or less hidden hostility often

(15) the more or less hidden hostility often 
causes marked impairment in the hypomanic individual’s ability to pursue some necessary task or to maintain an acceptable contact with family members. In this respect, therefore, dysphoric hypo-mania may cause as much clinically signiﬁ  cant impairment in 
social functioning as cyclothymia.
Mania without psychotic features
In mania, the elevated spirit seen in hypomania is often mixed with irritability and hostility. Jamison
(4) has described the change: 
‘Humor and absorption on friends’ faces are replaced by fear and concern. Everything previously (in the hypomanic state) moving with the grain is now against—you are irritable, angry, frightened, uncontrollable . . . ’ .Table 4.5.2.2  Manic symptoms as included in DSM-IV and ICD-10
Symptoms of mania DSM-IV ICD-10
1A Elevated mood + +

1B Irritable mood + +2 Increased self-esteem or grandiosity + +3 Decreased need for sleep + +4 Increased talkativeness + +5 Flight of ideas + +6 Distractibility + +7A Increased social activities or contacts + +7B Psychomotor agitation + +8 Risk taking behaviour + +9 Increased sexual activities _ +

SECTION 4  clinical syndromes of adult psychiatry 636
The psychomotor symptoms of mania are restlessness and less 
need for sleep. There is pressure of speech; the patient talks more and in a louder voice. There is intrusive behaviour, arguments, and attempts to dominate others. Expansiveness is manifested as increased self-esteem; for example, the patient clearly overestimates his or her own capacities or hints at unusual abilities. Jamison
(4)
has described how in periods of mania she did not worry about money: ‘The money will come from somewhere; I am entitled; God will provide. Credit cards are disastrous, personal cheques even worse . . . mania is a natural extension of the economy . . . So I bought precious stones, elegant and unnecessary furniture, three watches within an hour (in the Rolex rather than Timex class) . . . ’ .
T o be diagnosed as a manic episode, the disorder should last at

T o be diagnosed as a manic episode, the disorder should last at 
least a week. The criteria for mania are elevated or clearly irritable mood, and at least three of the symptoms listed in Table 4.5.2.2. These symptoms should be severe enough to cause markedimpairment of occupational functioning. Hospital admission is often needed to prevent the patient from harming him/herselfor others.
The psychomotor restlessness and the pressured speech in the 
dysphoric hypomanic state present a clinical picture of agitated depression, i.e. a mixed state (Fig. 4.5.2.1). The taste for talking is observed more frequently in females than in males, but otherwise no signiﬁ  cant differences are seen between males and females in 
the manic dimension (Fig. 4.5.2.1).
Mania with psychotic features
Psychotic states of mania are characterized by greater pressure of speech, more open hostility, severe agitation, no need for sleep, ﬂ ight of thoughts, severe distractibility, and grandiose delusions.

In younger people, psychotic mania is often misdiagnosed as schizophrenia.
In hospital, the increased social contact of manic patients is 
clearly different from the emotional bluntness of schizophrenics. The intrusive behaviour seen in severe mania is of an extremely 
dominating and manipulative nature, out of context with the setting. Hamilton found this to be one of the most important 
mania symptoms. Secondary persecutory delusions often develop. 
The expansive religious delusion ‘hearing God’ should bedifferentiated from the schizophrenic patient’s religioushallucinations.
Both DSM-IV and ICD-10 differentiate between mood-congruent 
psychotic symptoms (such as grandiose delusions of religion and voices supporting the patient’s superhuman powers) and mood-incongruent psychotic symptoms (which are often the secondary delusions of persecution mentioned above).
Mixed states

The mixture of manic and depressive symptoms is the essential feature of mixed states (Fig. 4.5.2.1). It is not necessarily a bipolar course of symptoms, but the mixture of depressive and manic symptoms nearly every day. DSM-IV requires that the duration of a mixed episode should be at least 1 week; ICD-10 requires at least 2 weeks.
Kraepelin described transitory moods of depression in acute 
manic states. Transitory moods of depression have been recorded in manic patients by use of a rating scale administered by the nursing staff. Such short-lived states of ‘depression’ in patients with acute mania should be referred to as ‘microdepressions’ and not mixed episodes. Winokur described ‘microdepressions’ very clearly:
 . . . If one allows a manic patient to talk, one will note that he shows ﬂ eeting episodes of depression embedded within mania (microde-

. . . If one allows a manic patient to talk, one will note that he shows ﬂ eeting episodes of depression embedded within mania (microde-
pressions). He may be talking in grandiose and extravagant fashion and then suddenly for 30 seconds breaks down to give an account of something he feels guilty about . . . His eyes will ﬁ  ll with tears but in 
15 to 30 seconds he will be back to talking in his expansive fashion.
Rapid cycling
DSM-IV has a speciﬁ  er for rapid cycling, which refers to patients 
with bipolar I or bipolar II disorders, who have experienced at least four episodes during the previous 12 months. The episode has to be demarcated by partial or full remission for at least 2 months or a switch to an episode of opposite polarity.

The clinical spectrum of the states of depression and mania has been described in Fig. 4.5.2.1 by the symptomatic dimensions of severity as validated by clinician-rated scales. Thus, symptom severity is a key issue of the spectrum of mood states.
The spectrum of mood polarity disorders covering the longitu-
dinal diagnosis of manic and depressive episodes is shown in Fig. 4.5.2.2. Recent research has demonstrated how important it is to recognize subthreshold states of mania and depression, as they can have a major impact on both social functioning and quality of life, since many patients with mood disorders spend much time in subthreshold disorders, i.e. cyclothymia, dysthymia, or neuroticism.
While the severity spectrum of the states of mania and
depression has been accepted as evidence-based, we still lack avalidation of the mood polarity spectrum in long-term follow-up studies.Box 4.5.2.2  The three stages of the acute manic episode as 
observed in untreated inpatients

XHypomania
 Increased well-being and/or irritable mood, more busy, pres-
sured speech, makes more telephone calls, seductive
XMania
 Nearly always pleasant and cheerful. Occasionally losing 
insight and cooperation, impulsive, angry, very hyperactive, less sleep, more pressure of speech, makes repeated telephone calls, racing thoughts, more expansive, some grandiosity
XMania with psychotic features
 Emotionally labile, can be very angry, very intrusive. 
Uncooperative, severely agitated, no sleep, very talkative, loud, ﬂ ight of thoughts, grandiosity, religious delusions ‘hearing 
God’ , sexually very preoccupied
(modiﬁ  ed from G.A. Carlson and F.K. Goodwin (1973), The stages
of mania. A longitudinal analysis of the manic episode, Archives 
of General Psychiatry ,28, 221–8.)

637
I wish to thank Jules Angst and Rasmus W. Licht for their valuable 
comments and suggestions during the revision of this chapter.
The greatest resource book for research is Goodwin, F.K. and Jamison, K.R. 
(2007). Manic depressive illness  (2nd edn). Oxford University Press, 
Oxford.
Other sources for further information are:
Marneros, A. and Goodwin, F.K. (eds.) (2005). Bipolar disorders: mixed 
states, rapid cycling and atypical forms . Cambridge University Press, 
Stein, D.J., Kupfer, D.J., and Schatzberg, A.F. (eds.) (2006). Textbook of mood 
disorders . American Psychiatric publishing, Washington, DC.
Ghaemi, S.N. (2003). The concepts of psychiatry. A pluralistic approach to
the mind and mental illness . Johns Hopkins University Press,
Baltimore.
 1. Bech, P . (1993). Rating scales for psychopathology, health status and 
quality of life . Springer Verlag, Berlin.

 2. Bech, P . (2005). The Bech-Rafaelsen Mania and Melancholia Scales 
in clinical trials: a 25-year review of their use as outcome measure in 
bipolar and unipolar patients. In Focus on bipolar disorder research
(ed. M.C. Brown), pp. 131–51. Nova Science Publishers, Hauppauge, New Y ork.
 3. Goodwin, F.K. and Jamison, K.R. (2007). Manic-depressive illness
(2nd edn). Oxford University Press, New Y ork.
 4. Jamison, K.R. (1995). An unquiet mind. A memoir of moods and 
madness . Knopf, New Y ork.
 5. James, W. (1890). Principles of psychology . Holt, New Y ork.
 6. Bech, P . (1998). Quality of life in the psychiatric patient . Mosby-Wolfe, 
London.
 7. Eysenck, H.J. (1958). A short questionnaire for the measurement of 
two dimensions of personality. Journal of Applied Psychology ,42, 14–17.

London.
 8. Klerman, G.L. (1981). The spectrum of mania. Comprehensive 
Psychiatry ,22, 11–20.
 9. Angst, J. (2007). The bipolar spectrum. The British Journal of 
Psychiatry ,190, 81–6.
10. Cassano, G.B., Rucci, P ., Frank, E., et al. (2004). The mood spectrum in 
unipolar and bipolar disorder: arguments for a unitary approach. The American Journal of Psychiatry ,161, 1264–9.
11. Kendler, K.S. and Gardner, C.O. (1998). Boundaries of major 
depression: an evaluation of DSM-IV criteria. The American Journal of 
Psychiatry ,155, 172–7.
12. Styron, W. (1990). Darkness visible. A memoir of madness . Random 
House, New Y ork.
13. Hamilton, M. (1960). A rating scale for depression. Journal of 
Neurology, Neurosurgery, and Psychiatry ,23, 56–62.
14. West, J.L.W (1998). William Styron. A life . Random House, New Y ork.

15. Benazzi, F. (2007). Bipolar disorder—focus on bipolar II disorder and 
mixed depression. Lancet ,369, 935–45.
16. Klein, D.N., Shankman, S.A., and McFarland, B.R. (2006). Classiﬁ  cation 
of mood disorders. In Textbook of mood disorders  (eds. D.J. Stein, 
D.J. Kupfer, and A.F. Schatzberg), pp. 17–32. American Psychiatric Publishing Inc., Washington, DC.
17. Angst, J., Adolfsson, R., Benazzi, F., et al. (2005). The HCL-32:
towards a self-assessment tool. Journal of Affective Disorders ,88,
217–33.
18. Carlson, G.A. and Goodwin, F.K. (1973). The stages of mania. 
A longitudinal analysis of the manic episode. Archives of General 
Psychiatry ,28, 221–8.4.5.3 Diagnosis, classiﬁ  cation, 
and differential diagnosis of the mood disorders

Varying expressions of mood disorders make for difﬁ  culties in 
deﬁ nition, diagnosis, and classiﬁ  cation. DSMIV and ICD10 formal 
classiﬁ  cations with decision rules (see Chapter 1.9) provide a struc-
ture but their underlying models may or may not be valid. This chapter therefore considers how mood disorders can be variably 
conceptualized and structured—an issue of intrinsic importance 
but also inﬂ  uencing identiﬁ  cation of causes and management. 
Some deﬁ  nitional and boundary issues are ﬁ  rst detailed prior to 
considering sub-typing and differential diagnostic issues.
(a) Depression
The term depression is extremely broad, variably deﬁ  ning an affect,

The term depression is extremely broad, variably deﬁ  ning an affect, 
mood states, disorders, or syndromes—as well as disease states. A depressed ‘affect’ usually occurs in response to a speciﬁ  c situation 
and is deﬁ  ned as a transient and non-substantive state of feeling 
‘depressed’ , ‘sad’ , or ‘blue’ .
Adepressed mood  is more pervasive, more likely to be experienced 
as unusual or atypical, associated with negative ideation (e.g. hope-lessness, helplessness, pessimism about the future), and may inﬂ  u-
ence behaviour. Its quintessential construct is lowering of the individual’s intrinsic level of self-esteem, with the extent of self-esteem lowering roughly equating to the severity of the mood state. Experienced by most people, it generally lasts only minutes to days in non-clinical situations.
Adepressive condition  (be it a disorder, syndrome, or disease) is

Adepressive condition  (be it a disorder, syndrome, or disease) is 
generally distinguished by a longer duration, more clinical (and more 
pathological) features, and distinct social impairment. A duration criterion ensures that a transient depressed mood state doesnot alone establish psychiatric ‘case’ status, with a minimumduration of 2 weeks capturing most conditions other than theso-called ‘adjustment disorders’ . Additional clinical features (detailed 
shortly) inform us about severity (e.g. ‘major’ and ‘minor’ depres-sive disorders) and sub-typing, while the social impairmentcriterion further cleaves ‘normal’ mood states from clinical depres-sive conditions.
At times, depressive conditions are described as primary or 
secondary , a distinction necessarily imprecise. We comfortably 
concede ‘secondary depression’ when depression emerges during the course of a substantive psychiatr ic condition (e.g. schizophrenia)

concede ‘secondary depression’ when depression emerges during the course of a substantive psychiatr ic condition (e.g. schizophrenia) 
or medical condition, or following certain aetiologically deﬁ  ned 
triggers (e.g. substance abuse). However, as depression is commonly contributed to by other psychiatric disorders (e.g. severe anxiety states) and primary psychosocial factors, it might be logical to also call these ‘secondary’ depressive disorders, and yet this rarely occurs. The term ‘secondary depression’ therefore generally imputes a substantive primary condition with depression as a clear-cut consequence.4.5.3 diagnosis, classification, and differential diagnosis of the mood disorders

SECTION 4  clinical syndromes of adult psychiatry 638
(b) Bipolar/unipolar depression speciﬁ  cs
Turning from cross-sectional to longitudinal deﬁ  nition, the course 
speciﬁ  er ‘bipolar’ is applied to those having had at least one manic 
or hypomanic episode, whether preceded or not by a depressive episode. Originally, Leonhard
‘monopolar’ (or ‘unipolar’) depression to distinguish those who had episodes of the melancholic sub-type of depression, but no manic episode. Regrettably, the term ‘unipolar’ depression is now used to deﬁ  ne a residual (i.e. non-bipolar) category, so heteroge-
neous as to be of limited meaning and utility.
(c) Mania/hypomania

As described in Chapter 4.5.2, such conditions are the converse of depression and fundamentally represent hedonistic, high energy states. Here self-esteem is almost invariably increased, the mood generally infectious, the individual energized or ‘wired’ , disinhibit-ed, with creativity and religiosity often enhanced, while psychotic features may be present.
Distinguishing ‘hypomania’ and ‘mania’ is imprecise in the 
formal classiﬁ  catory systems, as noted shortly. T o some theorists, 
the presence of psychotic features determines manic (as against hypomanic) status. Others subscribe to a dimensional model. For example, Goodwin and Jamison
(2) suggest that hypomania and 
mania differ little in mood components, but that cognition, per-ception, and behaviour differ in severity and manifestation.
(d) Bipolar categories

In recent years, bipolar disorder has been principally sub-categorized into bipolar I and bipolar II expressions, with ‘manic’ and ‘hypomanic’ episodes, respectively, deﬁ  ning the ‘highs’ . The 
term ‘bipolar III’ refers to a manic or hypomanic ‘switch’ on expo-sure to—or cessation of—an antidepressant drug and may reﬂ  ect 
a pure drug effect and/or a vulnerability to switching in those with a latent bipolar condition. Numerous other bipolar categories (e.g. IV , V , and VI) have been proposed in the last few decades.
(3)

(3)
Many describe a ‘hyperthymic’ bipolar type (where the individual tends to be frequently cheerful, overly talkative, extroverted, self-assured, and full of ideas). Whether this is merely an exuberant personality style or a mild or sub-clinical expression of bipolar disorder remains to be clariﬁ  ed. The growth in bipolar sub-types 
has led to the dimensional concept of a ‘bipolar spectrum’ .
(e) ‘Mixed states’
Here the individual with a bipolar disorder shows depressive fea-tures during a manic episode or manic features during a depressive episode. While sometimes used to describe the transition from one polar mood disturbance to another, it more commonly refers to the coterminous presence of manic and depressive features. Clinically, such patients more tend to report perturbing agitation rather than elevated mood in conjunction with depressive symptoms.
Depressive disorders: contrasting models
Unitary or binary?

The extended debate as to whether the depressive disorders are best conceptualized as comprising one or more distinct disorders warrants overview. The ‘unitarian’ model presupposes one depres-sive disorder, varying essentially by severity. The strict ‘binarian’ view postulated two separate types (i.e. ‘endogenous’/‘psychotic’ versus ‘neurotic’/‘reactive’). There were a number of ascriptions to the ‘endogenous’ (now termed ‘melancholic’) type. Firstly, as indi-
cated by its naming, its determinants weighted genetic and other biological factors rather than exogenous psychosocial factors. Secondly, that it had a distinctive pattern of (‘endogeneity’) symp-toms and signs—noted shortly. Thirdly, that it showed a preferen-tial response to physical treatments (e.g. antidepressant drugs and ECT) and less responsivity to psychotherapy. By contrast, the second ‘neurotic’ or ‘reactive’ depressive type was viewed as more

reﬂ ecting depression emerging as an interaction of a predisposing 
personality style and precipitating life-event stressors.
The debate was strongly inﬂ  uenced by Lewis’s clinical study
(4)
ﬁ nding no clear demarcation between depressive types, examined 
both cross-sectionally and longitudinally, thus delivering support to the unitarian view. The introduction of multivariate statistical approaches led to the debate being reactivated in the 1960s, with the so-called Newcastle School arguing strongly that their analyses supported a binary view. In a representative paper, Kiloh and Garside
(5) used a factor-analytic strategy to argue for separate 
‘endogenous’ and ‘neurotic’ depressive conditions. However, factor analysis is not ideal for developing a typology, in that it produces dimensions (here of symptoms) rather than groupings of patients. Subsequently, more appropriate strategies have been used, such as cluster analysis
(6) and latent class analysis,(7) and with those studies

(6) and latent class analysis,(7) and with those studies 
providing some support for separate classes. Critics suggest, how-ever, that such classes or subgroups could still be determined by severity or, even if sub-types can be identiﬁ  ed, question whether 
sub-classiﬁ  cation has any management importance.
(8–10)
This latter challenge is fundamental, taking us to the heart of any 
consideration of the diagnosis and classiﬁ  cation of the depressive 
disorders. T o the unitarians, as depression essentially varies only by degree, treatment choices (e.g. electroconvulsive therapy (ECT), antidepressant drugs, psychotherapy, or cognitive behavioural therapy) are commonly decided on the basis of severity. The oppos-ing argument—for conceding sub-types—was well put by Kendell,
(11)
who drew on historical analogies. For example, he noted that dis-tinguishing between cardiac and renal forms of ‘dropsy’ allowed prediction of those who would respond to digitalis.

(11)
Thus, if there are valid depressive sub-types, the contribution of 
putative psychosocial and biological risk factors may vary across each, and exert differential responses to differing treatment modalities. If the sub-typing model is valid, forcing homogeneity by creating dimensionally based categories such as ‘major depres-sion’ will ensure muddied results. As noted by Hickie,
(12) numerous 
studies of patients with DSM-deﬁ  ned ‘major depression’ have failed 
to demonstrate any coherent pattern of neurobiological changes, replicate key biological correlates, and demonstrate any speciﬁ  c 
pattern of treatment response outside inpatient treatment settings.
Approaches in the classiﬁ  catory systems
How then have the ofﬁ  cial classiﬁ  catory systems addressed such

How then have the ofﬁ  cial classiﬁ  catory systems addressed such 
a substantive issue? In developing the DSM-III system,(13) the 
working group was required to make a decision on the competing unitarian or binarian models. While the binarians were at the door, they had, until then, failed to prove their case and the DSM-III committee chose a compromise. Thus, DSM-III depression classiﬁ  -
cation was predicated on an initial dimensional component (i.e. ‘major’ versus ‘minor’ disorders). If criteria for a major disorder were met, second-order and more categorical decisions about the

639
presence of melancholia or psychotic depression were speciﬁ  ed. 
This model proved unsatisfactory for melancholia. For example, Zimmerman and colleagues
(14) noted that the DSM-III melancho-
lia criteria set, unlike the deﬁ  nition provided in the predecessor 
(DSM-II), ‘did not predict treatment response’ . Thus, the DSM-III-R
(15) criteria set for melancholia was revised to include com-
plete recovery after previous episodes, previous good response to somatic treatments, and no signiﬁ  cant personality disturbance, 
to overcome the lack of predictive validity by building into the deﬁ nition some of the ‘givens’ held by many clinicians about mel-
ancholia. However, the criteria set for melancholia developed for DSM-IV returned essentially to the DSM-III set, with limitations considered below. The contrasting system, ICD-10, is essentially based on a stricter dimensional or unitarian view of the depressive disorders—comprising ‘severe’ , ‘moderate’ , and ‘mild’ disorders.

During the extended debate as to whether a categorical and more 
‘biological’ type of depression exists—it was variably termed ‘endogenous’ , ‘endogenomorphic’ , ‘autonomous’ , and ‘melancholic’ depression. The last is probably preferable as numerous studies have quantiﬁ  ed few or no differences in the likelihood of those with 
‘endogenous’ and ‘non-endogenous’ depression reporting anteced-
ent life events, so arguing against any term weighting ‘internal’ or ‘external’ causes.
Whether psychotic (or delusional) depression is a ‘severe’ form

Whether psychotic (or delusional) depression is a ‘severe’ form 
of melancholia or a separate entity also remains problematic. DSM-III had a category ‘major depression with psychotic features’ for use when delusions or hallucinations are present or when there is ‘depressive stupor (the individual is mute and unresponsive)’ , thus viewing ‘psychotic depression’ as a sub-type of the generic ‘major depression’ category rather than a sub-type of melancholia. While ‘depressive stupor’ may be a useful marker or proxy for the condition, this criterion was not retained in DSM-III-R or DSM-IV , but is included in ICD-10. Two points argue for psychotic depression as a distinct entity: the presence of psychotic features, and its poor response to antidepressant medication alone and to neuroleptic medication alone in comparison to high responsive-ness to their combination.
(16)

(16)
A strict interpretation of the ‘binary’ view would place the 
non-psychotic, non-melancholic depressive conditions in a pure second class. However, rather than view this as a pure ‘type’ , this class is best regarded as a heterogeneous residue category (i.e. non-melancholic depression), with its heterogeneity expressed widely—across aetiological factors, clinical expression, and natural and treated history.
Classiﬁ  cation of affective mood disorders
Formal classiﬁ  cation—depressive disorders
Both ICD-10 and DSM-IV have multiple conditions and speciﬁ  ers. 
The ICD-10 system allows mild and moderate depressive episodes (with or without a ‘somatic syndrome’ conceptualized as reﬂ  ecting

The ICD-10 system allows mild and moderate depressive episodes (with or without a ‘somatic syndrome’ conceptualized as reﬂ  ecting 
‘melancholic’ features), and severe depressive episode (with or without psychotic symptoms). There are separate codes for a similar set of ‘recurrent’ disorders, while several ‘persistent’ mood disorders (including cyclothymia and dysthymia) and residual con-ditions are listed. DSM-IV has two principal ‘stem’ disorders (major depressive episode and dysthymia), with the ﬁ  rst having a number 
of optional specifiers including ‘with’ melancholic, catatonic, psychotic, or atypical features, as well as including disorders show-

ing longitudinal patterns of rapid cycling or a seasonal pattern. Both systems have categories for affective disorders secondary to organic disease, while DSM-IV includes mood disorders due to a general medical condition or substance use, or occurring in the post-partum period. Both classiﬁ  catory systems include adjustment 
disorders with depression.
Formal classiﬁ  cations are therefore built principally on severity, 
features of current episode, patterns of disorder expression over time, as well as persistence and recurrence. Few diagnoses are consistent across the ICD-10 and DSM-IV systems and, while each provides deﬁ  nitions that allow a ‘shared language’ to be used 
by clinicians and researchers, the extent to which their severity-
weighted groupings capture ‘meaningful’ depressive sub-types 
remains problematic.

For example, and as detailed elsewhere,
(17) ‘major depression’ has 
come to be viewed as an entity, sufﬁ  cient in and of itself for testing 
antidepressant therapies and to generate treatment recommenda-tions. Limitations to such a model become apparent if we consider the analogy of ‘major breathlessness’ , which could be a transient consequence of acute exercise, or reﬂ  ect quite differing pathological 
processes (e.g. asthma, pneumonia, or a pulmonary embolus) beneﬁ  ting from quite differing treatment approaches. Thus, a 
diagnosis of ‘major depression’ or ‘clinical depression’ is, in reality, a first-level domain diagnosis, and benefiting from secondary speciﬁ  cation. The latter tends to proceed on the basis of severity, 
but alternative and more categorical models have long been pro-posed as considered elsewhere in this chapter.

Formal classiﬁ  cation—bipolar disorders
The DSM-IV deﬁ  nition effectively requires an initial or previous 
manic episode for bipolar I disorder, while bipolar II disorder requires hypomanic episodes and one or more previous episode of major depression.
T o meet DSM-IV diagnostic status, manic episodes must have 
lasted 7 days and hypomanic episodes 4 days. Both ICD-10 and DSM-IV have course speciﬁ  ers for bipolar disorder containing 10 
and 4 subgroups, respectively. In addition to the number of subgroups, differences include a greater emphasis on distinguish-ing bipolar I and II in DSM-IV , and cyclothymia being listed as a ‘bipolar disorder’ in DSM-IV as against being a ‘persistent’ mood disorder overlapping with a personality style in ICD-10. Distinguishing ‘hypomania’ and ‘mania’ is regrettably imprecise in the formal classiﬁ  catory systems. Both DSM-IV

(18) and ICD-10(19)
disallow a diagnosis of hypomania if psychotic features are present 
but, conversely, do not require psychotic features for a diagnosis of mania. DSM-IV lists essentially similar clinical criteria (and criteria number cut-off) for hypomanic and manic episodes, but distin-guishes mania by the presence of marked impairment in social functioning (risking subjective judgement), requirement for hospi-talization (which is logically more a consequence than a deﬁ  ning 
criterion although it may have some proxy value), and the presence of psychotic features in a manic episode. As noted earlier, ICD-10 views hypomania as ‘an intermediate state without delusions, hallucinations, or complete disruption of normal activities’ .
Thus, formal ‘cleavage’ between bipolar I and II (and constituent

Thus, formal ‘cleavage’ between bipolar I and II (and constituent 
manic and hypomanic states) is largely dimensional in relation to clinical features and with some logical fallacies. Further, duration 4.5.3 diagnosis, classification, and differential diagnosis of the mood disorders

SECTION 4  clinical syndromes of adult psychiatry 640
criteria (i.e. at least 7 days for mania and at least 4 days for hypo-
mania in DSM-IV) do not appear sustainable. In recent years there have been many studies
(20) indicating that clinical deﬁ  nition of 
bipolar disorder is not dependent on the duration of the highs, and that imposing DSM-IV duration criteria for both mania and hypomania may exclude a signiﬁ  cant percentage of those with true 
bipolar disorder.
A sub-typing model for classifying depression
As detailed earlier, there are intrinsic difﬁ  culties in classifying

As detailed earlier, there are intrinsic difﬁ  culties in classifying 
depression according to any single model when it is a term encompassing normal mood states through to possibly categorical diseases, and when any imposition of a severity-based model raises problems about how to differentiate meaningful groups (e.g. ‘cases’ from ‘non-cases’). A personal mixed model is now detailed for consideration—one shaped by clinical experience and supported by research ﬁ  ndings. It is described in line with the ‘reasoning steps’ 
that a clinician might employ in assessing a potential depressive disorder.
(a) Step 1: Is a depressive disorder present?
For all the depressive disorders, the ﬁ  rst building block generally

For all the depressive disorders, the ﬁ  rst building block generally 
requires evidence of a depressed mood (although some with a melancholic or psychotic depression may deny ‘depression’). Useful questions include the following: ‘Do you feel depressed’?, ‘Has there been any change in your self-esteem or from the way you generally value yourself’?, and ‘Are you being more self-critical or harder on yourself than usual’?
The next clinical priority is to determine if the depression is 
sufﬁ ciently severe as to warrant ‘case’ status, and here the DSM-IV 
criteria for a major depressive episode have common acceptance in terms of representative symptoms and duration criteria. That criteria set lists the following:
X  four mood items (depressed mood, loss of interest or pleasure,

X  four mood items (depressed mood, loss of interest or pleasure, 
feelings of worthlessness or inappropriate guilt, recurrent thoughts of death, and suicidal ideation)
X weight changes
X sleep disturbance
X fatigue
X impaired concentration
X psychomotor disturbance
A positive diagnosis requires ﬁ  ve or more of the nine, evidence 
of functional impairment, and a minimum duration of 2 weeks.
(b) Step 2: If a depressive disorder is present, what sub-type?
If ‘caseness’ criteria are met, the next decision should be to deter-mine the diagnostic sub-type. We favour a three-class hierarchical model (i.e. respectively psychotic, melancholic, and a heteroge-neous non-melancholic class)—hierarchical in the sense that those in the two highest classes have class-speciﬁ  c features as well 
as possessing features of the subordinate classes. Clinical assess-ment then allows a sequencing process to diagnosis.
In essence: does this individual have a melancholic or non-

melancholic depression; are there psychotic features indicative of a psychotic depression? That sequence will now be detailed. The left half of Fig. 4.5.3.1 details the so-called ‘structural model’ . A shared mood disorder component is present and varying in severity across 
the three principal sub-types. However, sub-type distinction pro-ceeds on the basis of two class-speciﬁ  c components—psychomotor 
disturbance and psychotic features.
(c)  Step 3: Differentiating melancholic and non-melancholic 
In DSM-IV , the ‘melancholic features speciﬁ  er’ requires, in addi-

tion to a base diagnosis of major depression, either one of two A criteria and three (or more) of six B criteria, with most of the lat-ter comprising so-called ‘endogeneity symptoms’ . However, some such DSM criteria have limitations. Firstly, criterion A (loss of pleasure and/or lack of mood reactivity) is generally met by both ‘melancholic’ and ‘non-melancholic’ patients. Secondly, some crite-rion B features are vague. For example, ‘distinct quality’ is deﬁ  ned 
as a mood different to that experienced after ‘the death of a loved one’ , and is a negative deﬁ  nition (akin to deﬁ  ning ‘psychiatry’ as

as a mood different to that experienced after ‘the death of a loved one’ , and is a negative deﬁ  nition (akin to deﬁ  ning ‘psychiatry’ as 
‘not cardiology’). A second, ‘excessive or inappropriate guilt’ , is a concatenated descriptor, subsuming the excessive expression of normal guilt, as well as guilt held at an overvalued or delusional level. Others are non-speciﬁ  c (e.g. early morning wakening, signiﬁ  -
cant anorexia, or weight loss), being common in other psychiatric 
conditions (e.g. anxiety disorders) as well as in other expressions of depression. Further, as DSM-IV-defined major depression and melancholia share several similar features (e.g. anhedonia, psychomotor disturbance, weight loss), even those two conditions are poorly cleaved.
Features of melancholia:  Any improvement on DSM-IV distinc-
tion of melancholia would beneﬁ  t from identiﬁ  cation of features 
speciﬁ  c to—or distinctly over-represented in—melancholia. Nelson 
and Charney

(21) undertook a review of 33 studies using multivari-
ate statistical approaches to identify melancholic or ‘endogeneity symptoms’ . They found no support for appetite/weight loss and insomnia, little support for early morning wakening and ‘distinct quality’ , but some support for a severely depressed and non-reactive mood, loss of interest in pleasurable activities (or anhedonia), and psychotic features. The most strongly associated feature was psychomotor change (with retardation more consistently associated than agitation). When Rush and Weissenburger
(22) examined nine 
diagnostic systems for diagnosing melancholia or endogenous depression, the only common criterion in all nine was psychomo-tor retardation (with psychomotor agitation included in six). Our research
(23) has established that the speciﬁ  city of psychomotor

disturbance to ‘melancholia’ is dependent on measuring it as asign, with that diagnostic weighting more recently detailed and endorsed by others.
(24) Thus, and returning to a hierarchical model, Fig. 4.5.3.1 The structural and functional model of three depressive classes.
DA = dopamine; NA = noradrenalin; 5-HT = serotonin.
Neurotransmitter
DA
NA
5-HTClinical
feature
Psychotic
features
Psychomotor
Depressed
moodDepressive
Sub-type
Psychotic
Melancholia
Non-melancholic

641
differentiation between the non-melancholic and melancholic dis-
orders (on the basis of clinical features) appears assisted principally by the specific feature of behaviourally evident psychomotordisturbance. As measured by the sign-based CORE system,
(23) psy-
chomotor disturbance is reflected along three dimensions—impaired cognitive processing and motor retardation and agitation, although components are not mutually exclusive. For example, those with signiﬁ  cant agitation may have it present for much of the 
time or, and more commonly, have a base of retardation with inter-mittent epochs of agitation.
In younger individuals with true melancholia, overt psychomo-

tor disturbance is less distinctive, although they still tend to report distinct concentration problems. In addition to such ‘signs’ , symp-toms seemingly over-represented in melancholia include: distinct anergia often preventing the individual from getting out of bed to bathe; anergia and mood distinctly worse in the morning (i.e. diur-nal variation); and an anhedonic and non-reactive mood.
The non-melancholic disorders have no speciﬁ  c features—apart 
from some (e.g. mood reactivity) that are the converse of their expression in melancholic disorder (i.e. non-reactive mood). Thus, these conditions are effectively diagnosed by excluding the two higher order conditions of melancholic and psychotic depression.
(d) Step 4: Implications of the distinction
Classiﬁ  cation should never be sterile. It should at least provide us

Classiﬁ  cation should never be sterile. It should at least provide us 
with a lexicon and, ideally, inform us about management nuances. We suggest that there are important treatment implications associ-ated with distinguishing melancholic and non-melancholic disor-der. The right half of Fig. 4.5.3.1 offers a ‘functional model’ that operates in parallel with the ‘structural model’ . As detailed,
(25)

(25)
it assumes that if there is any neurotransmitter perturbation underpinning the non-melancholic disorders, then it is principally serotonergic in origin, shaping the hypothesis that there is no advantage in proceeding beyond a narrow-action Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant. It further assumes a greater noradrenergic contribution (and possibly dopa-minergic contribution) to melancholia, and shapes the hypothesis that broad-action antidepressants will overall be more effective than SSRI antidepressants—and any psychotherapy—for melan-cholic depression. Both hypotheses have been supported in a num-ber of trials and naturalistic studies
(26) arguing the importance of 
distinguishing the melancholic sub-type.
(e) Step 5: Distinguishing psychotic depression

In psychotic (or delusional) depression, the central mood compo-nent is generally even more severe than in melancholic depression but many will deny or minimize a depressed mood. A number of ‘endogeneity symptoms’ are also frequently more severe (particu-larly non-reactive mood, anhedonia, and constipation). One frequent feature in melancholic depression (i.e. diurnal variation of mood) is, however, rarely present at episode nadir, as the patient is more likely to be persistently depressed across the days. Observable psychomotor disturbance is present and generally dis-tinctly more severe than in melancholic depression. In some, the combination of the cognitive processing problems and motor change (retardation in particular) can give the impression of a dementing process, and provides an example of ‘pseudodementia’ .

The key class-speciﬁ  c feature , however, is the presence of psychotic 
features. Delusions are almost invariably present while hallucinations (auditory most commonly) are present in 10 to 20 per cent. DSM-
IV subdivides delusions and hallucinations as ‘mood congruent’ (where themes of guilt, disease, death, nihilism, and personal inad-equacy dominate) and ‘mood incongruent’ (where psychotic fea-tures appear independent of the depressive theme and might include persecutory themes, delusions of control, as well as thought insertion and thought broadcasting) states. It is important to 
emphasize that mood-incongruent states are common and do not, 
by themselves, necessarily challenge a diagnosis of delusional depression or argue for a schizophrenic illness of necessity.
A signiﬁ  cant percentage (approximately one-third) of patients

A signiﬁ  cant percentage (approximately one-third) of patients 
with psychotic depression develop constipation. In many it is a pri-mary feature (not merely a side-effect of psychotropic medication), and may serve as a nidus of delusional interpretation (e.g. the depressed patient who believes that their bowels have turned to concrete, or that they have a bowel cancer).
When psychomotor disturbance is extremely severe, it may not 
be possible for psychotic features to be elicited, particularly if the patient is mute. Many patients are difﬁ  dent about revealing psy-
chotic material, and here indirect questions can often be useful. In particular, pursuing the presence of ‘guilt’ can assist, with guilt here deﬁ ned as a sense of self-blame and not merely self-criticism,

together with a sense of remorse for wrong acts or omissions that are independent of any concern about potential evaluation by others. In psychotic depression, the guilt is more likely to be held at the level of an overvalued idea or at a formally delusional level. If direct inquiry does not elicit delusional material, then asking ‘Do you feel any sense that you deserve to be punished’? can help elicit previously unexpressed psychotic material.
Our ‘functional model’ (Fig. 4.5.3.1) argues that there is likely to 
be a greater dopaminergic (than noradrenergic and serotonergic) contribution to psychotic depression, a hypothesis supported by meta-analyses
(16,27) quantifying this condition as showing a 25 per 
cent response to an antidepressant alone, 33 per cent to an antipsy-chotic alone, and 80 per cent to their combination and to ECT.
(f)  Step 6: If a non-melancholic depressive disorder, can this 
class be sub-typed?

There is no generally accepted sub-typing system for this residual 
group, and where symptoms reﬂ  ecting the lower order mood 
construct dominate the clinical picture. In the absence of any class-speciﬁ  c features, any categorical sub-typing model is unlikely to be 
valid, and dimensional models more appropriate. But what are the salient constructs for dimensionalizing? DSM-IV and ICD-10 proceed largely on a severity dimension for the mood disorder (e.g. ‘major’ and ‘minor’) but also on patterns of recurrence and persis-tence, all appropriate candidate dimensions.
Historically, terms such as ‘neurotic depression’ and ‘reactive 
depression’ were used, with the former emphasizing a pre-morbid style of neuroticism and high anxiety, and the latter deﬁ  ning 
depression developing largely in response to life-event stressors. This suggests another set of candidate constructs, dimensionalizing

depression developing largely in response to life-event stressors. This suggests another set of candidate constructs, dimensionalizing 
both personality and severity of stress components—and model-
ling their interaction.
Several earlier studies argued for some clinical utility emerging 
from such a model. Thus, an early factor-analytic study
(28)
suggested both a ‘hostile’ type (evidenced by irritability as well as anxiety) and an ‘anxious-tense’ type. Blashﬁ  eld and Morey
(29)4.5.3 diagnosis, classification, and differential diagnosis of the mood disorders

SECTION 4  clinical syndromes of adult psychiatry 642
reviewed 11 cluster analytic studies suggesting separate ‘hostile’ 
and ‘anxious’ depressive subgroups. In an extensive review of the then published studies, Roth and Barnes
(30) suggested three princi-
pal subgroups, with depression associated with a personality disor-der, in addition to ‘hostile’ and ‘anxious’ depression.
While such ‘hostile’ and ‘anxious’ subgroups have been identiﬁ  ed 
for a lengthy period, clear and consistent descriptions are lacking. Grinker et al.
(31) described those with ‘hostile’ depression as unap-
preciative, actively angry, provocative, and making excessive demands of—and complaints about—their therapists, suggesting a personality disorder contribution. The second (‘anxiety’) subgroup is variably interpreted as deﬁ  ning either those with an anxious per-
sonality or temperament, or the presence of signiﬁ  cant cotermi-
nous anxiety symptoms when primarily depressed.

The model we favour is one that respects historical description 
(i.e. ‘reactive’ versus ‘neurotic’) but develops the ‘personality’ contribution beyond the simple diagnostic allocation of ‘neurotic depression’ .
T erms such as ‘reactive depression’ or ‘situational depression’ (or 
as used in DSM-IV and ICD-10, ‘adjustment disorder’) concede that some individuals develop a non-melancholic depressive disor-
der largely or purely as a consequence of a stressful life event, which 
may produce, trigger, and/or maintain depressive episodes. In an empirical study,
(32) the authors were unable to establish clinical, 
family history, and even life-event stress differences between those with ‘situational’ and ‘non-situational’ major depression. Our research
(33) indicated that for the acute reactive ‘disorders’ , the

(33) indicated that for the acute reactive ‘disorders’ , the 
impact emerged less from the severity of the stressor and more from its perceived ‘meaning’ or ‘salience’ . We suggested a cognitive ‘lock and key model’ , whereby individuals may be predisposed by perturbing developmental events such as a highly judgemental par-
ent (creating ‘locks’). In adult life, exposure to a mirroring situa-tion (e.g. a judgemental boss) might act as a ‘key’ for precipitating a 
‘reactive’ depression. For more chronic ‘situational depression’ sce-narios, here we presume that the stressor is a chronic one and/or that the stressor induces a ‘learned helplessness’ mind set in the individual, where they believe that it does not matter what they do or attempt to do—there will be no impact on outcome—and they develop a sense of ‘powerlessness’ along with depressive symptoms.
A spectrum model
In modelling non-melancholic disorders reﬂ  ecting a personality

In modelling non-melancholic disorders reﬂ  ecting a personality 
contribution, we suggest the utility of a ‘spectrum’ model, a term variably used but which argues for a continuum between tempera-ment/personality style and symptom states,
(34) or some level of 
inter-dependency. This spectrum model views certain biological factors as shaping temperament and personality style—which then shape surface marker symptoms during a non-melancholic depres-sive episode. An earlier research report
(35) identiﬁ  ed those present-

ing with an ‘irritable/hostile’ depression as being more likely to have a cluster B personality and to report ‘acting out’ behaviours when stressed (i.e. demonstrating a ‘short fuse’ response to stress). By contrast, those with an ‘anxious depressive’ spectrum disorder appeared more likely to internalize anxiety. They tended to have shown shyness and behavioural inhibition in childhood, to have high rates of lifetime anxiety disorders, score high on trait anxiety, view themselves as ‘worriers’ , ‘nervy’ , or ‘tense’ , and to rate as having a cluster C personality style. When stressed, they were some-

what more likely to ‘act in’ by becoming quiet, retiring to their room, crying, and ‘stewing’ . Thus, anxiety was evident both in the temperament pattern and in the prominent symptom pro-file when depressed—demonstrating the ‘spectrum’ . The sug-gested profile of these spectrum disorders is not only important for clinical consideration, but in facilitating research into pos-sible neurobiological determinants and to consider any treat-ment specificity. For example, Blashfield and Morey
(36) reviewed 
studies indicating that ‘anxious depressives respond well to major and minor tranquillizers but not to tricyclics, while hos-tile depressives show little improvement with conventional drug therapies’ . Further, Fava et al.
(37) reported that anxious depres-
sives were more likely to be responders to a selective serotonin reuptake inhibitor (SSRI) than other depr essive expressions 
(including ‘hostile depression’).
We have more recently pursued the ‘spectrum model’ for

non-melancholic disorders beyond the two candidate groupings (i.e. hostile/irritable and anxious depressive) considered above. Both clinical observation and literature review indicated eightpredisposing personality styles
(38) but an application study(39)
suggested that the spectrum model could be supported up to asix-factor personality model. The latter spectrum model is now detailed.
Those who scored high on the personality measure of ‘anxious 
worrying’ were, when depressed, indecisive, and self-blaming, as well as feeling anxious and tense. Those high on the ‘irritability/snappiness’ personality dimension were likely, when depressed, to be irritable and impulsive. Rather similar personality dimensions of ‘personal reserve’ and ‘social avoidance’ identiﬁ  ed some differen-
tial coping responses apart from a shared social withdrawal

tial coping responses apart from a shared social withdrawal 
response, with the former avoiding others and losing interest in people, while those high on social avoidance reported avoiding 
pleasurable activities. Those high in ‘perfectionism’ were more like-ly to focus on trying to solve the problem and to seek distraction. The sixth personality style beneﬁ  ts from more detailed consider-
ation as it informs us about the nature of ‘atypical depression’ , a condition which—while listed in DSM-IV and held to show a spe-ciﬁ c response to monoamine oxidase inhibitor antidepressant 
drugs—has been quite variably interpreted over time.
(40) In that 
review, we argued for the primacy of the personality style of ‘rejec-tion sensitivity’ . In our spectrum study,
(39) those high on ‘rejection 
sensitivity’ were distinctly more likely to report some of its charac-

teristic features (e.g. food cravings, hypersomnia), but also a set of cognitive extensions of their personality style (e.g. a tendency to feel abandoned, rejected, and put down) as well as distinct self-consolatory strategies (e.g. spending money, seeking support, and even crying).
While such a spectrum model is not a categorical one (in cir-
cumscribing ‘pure’ depressive conditions) nor sufﬁ  ciently consis-
tent in expression to deserve endophenotypic status, such ‘fuzzy 
set’ patterning may have clinical implications in terms of assisting a 
richer diagnostic formulation and in providing therapies that 
address any predisposing personality style, rather than merely treat the surface marker of non-melancholic ‘depression’ . Much research will be required to determine if candidate expressions show any differential response to contrasting antidepressant strategies,

643
A sub-typing model for classifying bipolar 
disorders
As considered earlier, the formal ofﬁ  cial classiﬁ  catory systems fail 
to provide pristine cleavage between bipolar I and bipolar II disor-ders. We brieﬂ  y describe a model that supports an historical 
approach to this issue (by preserving the deﬁ  nition of mania—and 
bipolar I status—to those who have had psychotic features during a 
‘high’) and which links the bipolar disorders with psychotic and melancholic depression.
The ‘isomer model’ illustrated in Fig. 4.5.3.2 builds on studies 
suggesting that ‘bipolar depressive episodes’ are highly likely to be psychotic or melancholic in type, albeit with some differences in that individuals not infrequently report ‘atypical features’ of hypersomnia and food cravings rather than more characteristic melancholic features of insomnia and appetite loss. The model was further shaped by ﬁ  ndings derived in one clinical sample.
(41) Firstly,

(41) Firstly, 
bipolar patients who had experienced a psychotic ‘high’ had a 50 per cent chance of having a depressive episode with psychotic features. Secondly, of the bipolar patients who had never been psychotic during a high, none had experienced psychotic features.
The ‘isomer model’ therefore posits two contrasting ‘mirror image 
states’ . Those with bipolar states oscillate across parameters of energy 
and mood (elevated in highs, depressed in lows). More speciﬁ  cally, 
individuals with bipolar II disorder oscillate between non-psychotic 
depression and hypomania—never experiencing psychotic depres-
sion or psychotic mania. By contrast, those with bipolar I disorder 
have had psychotic manic episodes (by deﬁ  nition) and, when 
depressed, are at increased risk of having psychotic episodes.
The advantage to the model is that it respects and formalizes the

The advantage to the model is that it respects and formalizes the 
historical view of regarding the presence or absence of psychotic features during a high as distinguishing mania and hypomania (and respective bipolar I and II disorders). Further, it suggests that aetiological studies might well focus on pursuing the nature of two oscillators—one of mood and energy, and one of psychotic features. Thirdly, it offers a template for pursuing management options for the two differing bipolar disorders. Currently, there are many treatment guidelines for managing bipolar I—but only informal templates for managing bipolar II disorder
(42)—and it 
may be unwise to extrapolate such bipolar I guidelines for managingbipolar II disorder.Differential diagnosis and ascertainment 
difﬁ culties
The three key features of lowered self-esteem, increased self-criti cism,

The three key features of lowered self-esteem, increased self-criti cism, 
and a depressed mood distinguish depression phenomenologically from states such as grief or bereavement—where there is a distinct sense of ‘loss’ of something valued, but no primary ‘loss’ of self-esteem. They also assist phenomenological differentiation from anxiety, where the individual is more likely to report a sense of insecurity, fear, apprehension, worry, panic, or of ‘going mad’ . Subsequent questioning of clinical symptoms and observation should clarify if a clinical syndrome exists, its diagnostic sub-type and—from a longitudinal perspective—whether the individual has a unipolar or bipolar course.
At the practical level, such a deﬁ  nitional approach may fail in 
certain groups. A percentage of those with psychotic or melancholic depression appear more emotionally blunted and ‘ﬂ  at’ rather than

certain groups. A percentage of those with psychotic or melancholic depression appear more emotionally blunted and ‘ﬂ  at’ rather than 
depressed. They may deny depression, self-blame and worthless-ness, and instead note a lack of feeling (or vitality), sluggishness, enervation, or emphasize physical states, such as anergia. Less commonly, they may evidence ‘corporization’ by Schneider,
(43)

(43)
with reports of pain or physical sensations in the head, chest, or stomach. As noted earlier, others may have such profound psycho-motor disturbance that they do not respond to questioning and appear as if they have a dementia (here a so-called ‘pseudodementia’). In such instances, pursuit of proxy items (severe psychomotor disturbance, pathological guilt, overvalued ideas) may assist. If unsuccessful, the diagnosis may require corroborative reports and clinical observation, as well as certain investigations (e.g. CT or MRI scans, single-photon emission CT scans, EEG) to exclude a dementia. In a percentage of the elderly, however, a depressive episode and dementia may coexist (particularly a vascular demen-tia), and reﬂ  ect a shared aetiological process.
Secondly, there are some patients and certain cultures where 
psychological issues are either denied or expressed somatically, although careful and directed questioning about central depressive

psychological issues are either denied or expressed somatically, although careful and directed questioning about central depressive 
descriptors will usually clarify the possibility. If unsuccessful, diag-nostic clariﬁ  cation may require corroborative reports and clinical 
observation.
Thirdly, it is commonly difﬁ  cult to deﬁ  ne ‘clinical depression’ in 
those with a medical illness. Here, general depression criteria sets risk false-positive diagnoses by including certain features which may be secondary to the medical illness (e.g. fatigue, insomnia, anorexia) rather than reﬂ  ecting depression per se . Common correc-

tive strategies include the ‘aetiological approach’ , where only symp-toms viewed as independent of the medical condition are counted, the ‘exclusive approach’ , eliminating potentially confounded items such as anorexia, the ‘inclusive approach’ , where all symptoms are counted irrespective of their origin, and the ‘substitutive approach’ , excluding features that could be due to the medical illness and substituting features such as social withdrawal and crying.
In some cases where depression has been established, the salient 
clinical difﬁ  culty is in determining whether depression is or is not 
the primary disorder in those with concomitant major medical problems, excessive alcohol intake, organic central nervous system disease, and certain psychiatric conditions (e.g. anxiety states, depressive personality disorder). Clinical judgement is generally 
Fig. 4.5.3.2 The isomer model for conceptualizing bipolar I and bipolar II 
conditions. (Reproduced from Parker et al.(41))

Bipol ar I
Bipol ar II
Mel ancholi aPsychotic Feature s
Psychotic
Depre ssionPsychotic Feature sPsychomotor Di sturbance
(Elev ated mood, high energy)
Psychomotor Di sturbance
(Anhedonic, anergic)4.5.3 diagnosis, classification, and differential diagnosis of the mood disorders

SECTION 4  clinical syndromes of adult psychiatry 644
required with two alternate logical approaches: either weighting 
the disorders hierarchically or sequentially. The hierarchical approach assumes that the more severe disorder is the primary one, while the sequential approach weights the antecedent condition (e.g. organic disorder, schizophrenia, anxiety). Acceptance of one approach does not logically bind the clinician to any therapeutic 
consequence (such as necessarily treating only the more severe or primary condition).
Mania/hypomania
The differential diagnoses for manic states essentially includeother psychotic conditions (e.g. schizophrenia, drug-induced

psychosis) and, rarely, a primary organic state. While cross-sectional dissection of the phenomenology can be helpful, thereis wisdom in also weighting the longitudinal course. Thus, those with manic states are more likely to describe complete restoration of function between episodes (of mania and/or depression),while this is less likely for those with schizophrenia. Deﬁ  nitive
distinction is not always possible, and a diagnosis of ‘schizoaffec-tive’ disorder may then be appropriate. In severe mania, an ‘organic’ picture may be suggested, and require exclusion of a dementia or delirium.
The differential diagnosis of hypomanic states is often quite dif-
ficult. Questioned about having ‘highs’ often elicits defensive response from those with true states, while some depressed people 
will present a remission to a euthymic state as a ‘high’ . Highly

will present a remission to a euthymic state as a ‘high’ . Highly 
creative people may afﬁ  rm many hypomanic descriptors when 
possessed by the muse (e.g. less need for sleep, feeling creative, and overconﬁ  dent, being enthused and energized), as may those with a 
distinctly extroverted or cyclothymic personality when stimulated. Some patients with a cluster B personality style (especially of the borderline type) may also describe mood states that approximate to hypomania. Clariﬁ  cation is probably best assisted by a sequence

of strategies, including asking the individual about times when, neither depressed nor feeling normal, they have states of feeling overly ‘energetic and wired’ , that they have an appropriate number of concomitant criterion features during such highs, that there was a ‘trend break’ where ‘highs’ became a new phenomenon (most commonly mid-adolescence or later), and that—during their highs—any usual level of anxiety melts away, and by interviewing a corroborative witness.
Current formal classiﬁ  catory systems list a large number of mood 
disorders, with criteria designed to assist diagnostic reliability. Most reﬂ ect attempts to create classes on the basis of severity-weighted 
dimensional models. T erms such as ‘major depression’ and ‘unipolar depression’—as well as ‘bipolar spectrum disorder’—have achieved acceptance in recent years, for such diagnoses are easily made (and easily reiﬁ  ed), but the limitations inherent to their

heterogeneity should not be ignored. Until the dissonance between the formal classifications and clinician-derived models has been resolved, practitioners should proceed by recognizing the advantages and limitations to competing approaches. A functional classiﬁ  catory system should have clinical utility, going beyond 
mere description and informing the clinician about treatment differentiation.Further information
Parker, G. and Manicavasagar, V . (2005). Modelling and managing the 
depressive disorders. A clinical guide . Cambridge University Press, 
Parker, G. (2007). Modelling and managing bipolar II disorder: a clinical 
guide . Cambridge University Press, Cambridge (in press).
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A clinical guide . Cambridge University Press, Cambridge.
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the structure of the depressive states. Zentrallblat für Neurologie, 
Psychiatrie ,59, 281.4.5.4 Epidemiology of 
The Global Burden of Disease, which is a comprehensive assessment

The Global Burden of Disease, which is a comprehensive assessment 
of mortality and disability from diseases and injuries in 1990 and projected to 2020, highlights the importance of mood disorders for the world. Using the measure of disability-adjusted life years, it was determined that unipolar major depression was the fourth leading cause of disease burden in the world. It was also projected that, in the year 2020, unipolar major depression would be the second leading cause of disease burden in the world. Disability-adjusted life years is based on both mortality and disability. If one looks at disability alone, then unipolar major depression was the leading cause of disability in the world in 1990, and bipolar disor-der was the sixth leading cause. Across the world, 10.7 per cent of disability can be attributed to unipolar major depression and, in developed countries, unipolar major depression contributes

to nearly 20 per cent of disease burden in women aged from 15 to 
44 years.
(1)
The mood disorders have received considerable attention in psy-
chiatric epidemiology over the last 25 years. These received partic-ular attention in the ﬁ  ve-site United States National Institutes of 
Mental Health Epidemiologic Catchment Area Study ( ECA ), as 
well as in the epidemiological studies in other countries around the world that used the ECA methodology. Mood disorders also received particular attention in the National Comorbidity Survey (NCS ) in the United States, in the National Psychiatric Morbidity 
Survey of Great Britain, and most recently in the World Mental Health Survey ( WMH ) across many countries. Thus, there is sub-
stantial data from around the world on the epidemiology of these disorders. In addition, many of the population-based twin regis-tries, such as in Virginia (USA), have also paid particular interest to mood disorders and have the additional advantage of being able to

consider genetic as well as environmental risk factors.
While classical bipolar disorder with episodes of euphoric mania 
interspersed with episodes of depression is one of the clearest clini-cal syndromes in psychiatry, the boundaries of bipolar disorder remain contested. As case deﬁ  nition is central to epidemiology, all 
the contested boundaries of bipolar disorder could inﬂ  uence preva-

lence rates and our understanding of risk factors. Some of the major boundary issues for bipolar disorder include the overlap of bipolar disorder with psychotic features, with schizoaffective disorder and schizophrenia, and the overlap of bipolar disorder with unipolar major depression when patients who present primarily with depres-sion have brief or mild episodes of hypomania. There is also an overlap of bipolar disorder with apparent personality disorder, especially Cluster B personality disorders such as borderline and narcissism, and the issue of when hyperthymic personality merges into bipolar disorder.
(2,3)When bipolar disorder is comorbid with 
substance abuse there are also important diagnostic issues.4.5.4 epidemiology of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 646
Another important issue in determining caseness of bipolar dis-
order for epidemiological surveys is symptom pattern and duration. A number of the diagnostic instruments for assessing bipolarity in population surveys limit the questions on mania to a type of symp-tom proﬁ  le characterized by euphoria, grandiosity, increased energy, 
and decreased sleep. Whether the commonly used epidemiology interviews adequately detect those individuals who have manic episodes characterized by irritability, anger, and activation is very debatable. The other key diagnostic issue is what criteria are used to categorize the minimum duration for hypomania; is four days too long, is even two days too long? Furthermore, as insight is sometimes impaired in hypomania and mania, and as these are low prevalence disorders, the accuracy of case detection of bipolar dis-orders in populations remains an issue for further research.
(4)

(4)
Population studies such as the ECA, and its related cross-national studies, and the NCS reported that the lifetime prevalence of bipolar disorder varies from 0.3 to 1.5 per cent. The NCS data include only bipolar I data, while the ECA includes bipolar I and bipolar II disorder.
(4,5) In all studies, the six-month prevalence is 
not much lower than the lifetime prevalence of bipolar disorder. These ﬁ  ndings reﬂ  ect the high degree of chronicity and/or recur-
rence associated with bipolar disorder. Broader deﬁ  nitions of 
mania/hypomania have resulted in lifetime prevalence rates increasing to about 4 per cent.
(6)
In these population studies, the mean age of onset of bipolar dis-
order has varied from 17 to 27 years. However, as age of onset is not normally distributed, the mean is a slightly misleading variable; in clinical samples, while the mean age of onset may be in the twenties, the most common age of onset are the teenage years.

In bipolar disorder, the prevalence in males and females is similar. 
This is in contrast to the reasonably consistent female excess found in major depression.
Comorbidity
In the NCS, all identiﬁ  ed bipolar I individuals suffered from at least 
one, and often up to three or more, comorbid disorders. The most common comorbid disorders included the full range of anxiety disorders, alcohol and drug dependence, and conduct disorder or other antisocial behaviours.
Alcohol and drug abuse and/or dependence are commonly 
comorbid with bipolar disorder. Old studies found that binge 
drinking was especially common in bipolar individuals and that 
this binge pattern of drinking was more associated with manic 
episodes than with depressive episodes. Clinical studies ﬁ  nd that 
bipolar patients with comorbid substance dependence are less compliant with prescribed mood stabilizers and have more fre-
quent hospital readmissions. Stimulant abuse/dependence rates are

quent hospital readmissions. Stimulant abuse/dependence rates are 
especially increased in bipolar disorder.
Individuals with bipolar disorder have the full range of anxiety 
disorders, including phobias, panic disorder, and obsessive–compulsive disorder. Perhaps surprisingly, comorbid rates of these anxiety disorders tend to be higher in bipolar disorder than in major depression.
Another area of high comorbidity with bipolar disorder is that of 
childhood conduct disorder and attention deﬁ  cit disorder. One of 
the issues in understanding this high rate of comorbidity is whether childhood conduct disorder and/or childhood attention-deﬁ  cit 
disorder are sometimes the ﬁ  rst manifestations or precursors of 
bipolar disorder. Certainly, if the pattern of conduct-disorder 
symptoms or attention-deﬁ  cit symptoms is episodic rather than

symptoms or attention-deﬁ  cit symptoms is episodic rather than 
consistent over time, the issue becomes whether these are not early manifestations of bipolar disorder rather than truly independent comorbid conditions. The other key diagnostic controversy in this area is the status of juvenile or childhood bipolar disorder.
Use of health services

In the ECA study, 39 per cent of those with bipolar I or bipolar II disorders received outpatient psychiatric treatment within 1 year and about 10 per cent would receive inpatient treatment within a 6-month period. In the NCS study, 45 per cent of those with bipolar disorder had received psychiatric treatment in the previous 12 months; although 93 per cent reported lifetime treatment for their bipolar disorder. However, both of these studies suggest that more than half the individuals with bipolar disorder are not currently in psychiatric treatment and, given the high morbidity and mortality associated with bipolar disorder, this is of major concern.
(4)
Risk factors for bipolar disorders

(4)
In considering the risk factors for bipolar disorder, it is useful to separate risk factors into those that are risk factors for lifetime vulnerability (for example genetic factors) and those that are risk factors for the onset of an episode of depression or mania (for example, life events). Thus, in determining risk factors for lifetime vulnerability, genetic factors constitute the largest single risk factor. However, if one is considering who is vulnerable to an episode of mania over the next six months, genetic factors will play a relatively smaller part and predictions may be best based on other factors such as past history, childbirth, being treated for depression with antidepressant medication, and the approach of spring or summer. Genetic risk factors are discussed further in Chapter 4.5.5.
Although organic factors, such as some type of central nervous 
system damage, are unusual risk factors in young adults, in late-

onset bipolar disorder (age of onset more than 50 years) organic 
disease of the central nervous system is an increasing factor for the development of mania. In younger adults, AIDS and head injury are two important aetiological factors in a limited number of cases of bipolar disorder.
Risk factors for manic episodes in people with 
bipolar disorder
A range of other biological factors are particularly relevant risk 
factors to the onset of episodes of illness, but they may contribute a relatively small part to lifetime vulnerability. Many women have their ﬁ  rst episode of depression or mania in the postpartum period.

While a limited number of women may have manic episodes limited to the postpartum period, postpartum episodes of mania are more commonly part of a long-term bipolar disorder and these women will have episodes both precipitated by childbirth and at other times 
in their life. Indeed, in the postpartum period, having a history of bipolar disorder is one of the strongest risk factors for the develop-ment of a postpartum psychosis.
There is substantial evidence that seasonal patterns inﬂ  uence the 
onset of manic and depressive episodes. There are consistent

647
ﬁ ndings of an excess of manic episodes in late spring and early 
summer. T o date, however, the nature of the environmental factors that inﬂ  uence this late spring, early summer peak of manic episodes 
is less clear.
There is also substantial evidence that disruptions of normal 
biological rhythms may precipitate the onset of manic or depressive episodes. This has been documented in relation to international travel involving east–west or west–east travel with disruption of circadian rhythms. Disruption of circadian rhythms through shift-work or other factors, which disrupt the normal sleep cycles, may also be important triggers to the onset of episodes of mania. These ﬁ ndings have led to the development of a social rhythm metric, 
as an adjunct to interpersonal psychotherapy (interpersonal social rhythms therapy) as a treatment for individuals with bipolar disorder.
Adverse life events have been well documented to be precipitants

Adverse life events have been well documented to be precipitants 
of manic episodes, as well as depression. It appears that life events are more likely prior to the ﬁ  rst or second episode of mania and are 
less likely later in the course of illness. The critical factor in life events triggering mania may be whether there is associated sleep disruption, rather than the ‘psychological’ meaning of the event.
A key issue for the epidemiology of depressive disorders is deﬁ  ning 
the boundaries of major depression and dysthymia. Depressive symptoms in the community are common, and deﬁ  ning both the 
symptom count and the duration at which depressive symptoms count as part of a clinical disorder is arbitrary. When Kendler and Gardner
(7) examined the boundaries of major depression as deﬁ  ned 
by DSM-IV in a population-based twin sample of women, they f ound

that, if a twin had four or fewer depressive symptoms, syndromes composed of symptoms involving no or minimal impairment, and episodes lasting less than 14 days, then the individual’s co-twin was still at an increased risk of major depression. Kendler and Gardner concluded that they could find no empirical support for the DSM-IV requirement of duration for two weeks, ﬁ  ve symptoms, or 
clinically signiﬁ  cant impairment. These authors suggested that 
major depression, as articulated by DSM-IV , may be a diagnostic convention imposed on a continuum of depressive symptoms of varying severity and duration. Wainwright et al.,
(8) using data from

(8) using data from 
the National Psychiatric Morbidity Survey of Great Britain, have also suggested that research should move beyond a binary decision of case versus non-case, and utilize a probablistic measure of psychiatric case status, replacing the arbitrary threshold with a smooth transition. This type of approach allows the beneﬁ  ts 
of syndrome diagnosis to be retained, while not falling into the dilemma of an arbitrary threshold that lacks validity.
Provided that one accepts the arbitrary deﬁ  nition of major

Provided that one accepts the arbitrary deﬁ  nition of major 
depression, then determining the rates of current depressive disor-ders is not especially problematic. However, there are major meth-odological issues involved in determining whether an individual has ever had a lifetime episode of major depression. Lifetime prev-alence rates vary from 4.4 per cent in the United States ECA study, to 17.1 per cent in the NCS, and to over 30 per cent in Kendler’s 
Virginia twin sample of women. In part, subjects in the community 
may forget or fail to report past episodes of major depression (recall bias), and the manner in which the questions are asked may impor-
tantly inﬂ  uence lifetime rates of depression. In the Diagnostic

tantly inﬂ  uence lifetime rates of depression. In the Diagnostic 
Interview Schedule, which was used in the ECA, respondents were asked about lifetime symptoms, a lifetime diagnosis was made, and then recency of the lifetime diagnosis was determined. More recent diagnostic interview schedules, such as the Composite International Diagnostic Interview, ﬁ  rst ask about current depressive symptoms 
and then, having ‘primed’ individuals about depressive symptoms, 
go on to enquire about past depressive episodes. Interviews that 
follow the schedule of ‘priming’ before asking about past episodes appear to obtain considerably higher rates of lifetime major depression. Determining lifetime rates of depression with greater precision is an important task, as the vulnerability to depression conferred by risk factors such as genetic factors and childhood experiences may be wrongly estimated if lifetime rates of major depression are imprecise. For instance, when Kendler et al.
(9) exam-

(9) exam-
ined the heritability of major depression and corrected for the moderate reliability of a lifetime diagnosis of major depression, the heritability estimate increased from 40 per cent to over 70 per cent. As concluded by Kendler, major depression is not a disorder of high reliability and moderate heritability, but is a diagnosis of moderate reliability and high heritability.
DSM-IV allows major depression to be further subclassiﬁ  ed into 
subtypes, such as melancholia, atypical, psychotic, and by severity and recurrence. Most of the traditional epidemiology studies have tended to ignore the issue of subtyping major depression. Recently, however, the issue of the atypical depression subtype has received particular attention in the study of the Virginia twins and in the NCS. In both these studies, latent class analysis su ggests that atypical 
depression is a distinct subtype with several distinctive features, 
such as higher rates of parental alcohol- and drug-use disorders,

such as higher rates of parental alcohol- and drug-use disorders, 
higher interpersonal dependency, and higher rates of conduct disorder. If risk factors for atypical depression are, in part, distinct from risk factors for other subtypes of major depression, then for epidemiology to contribute to an understanding of aetiology it will be important to undertake further work on depressive subtypes.
(10)
In the ECA, the six-month prevalence of major depression across ﬁ ve sites was 2.2 per 100. In ECA equivalent studies the six-month 
prevalence rate ranged up to 5.3 per 100. In the NCS, the 1-month prevalence of a major depressive episode was 6.1 per 100.
(11) In the 
National Psychiatric Morbidity Surveys of Great Britain, the one-week rate of a depressive episode was 2.1 per 100.
(12) T ogether, 
these studies would suggest that the current rate of major depres-sion is in the realm of two to ﬁ  ve per cent.

The estimates of the lifetime rate of major depression are much 
more variable. The lowest rate reported is 4.4 per 100 from the ECA study, while, in the study of Virginia twins, the lifetime rate of major depression is over 30 per cent. It is reasonable to believe that the true lifetime rate of major depression is probably in the realm of 10 to 20 per 100, but caution should be exercised in expressing lifetime rates of depression with undue precision.
These rates of major depression may also be lower if the rate of 
bipolar disorder is higher. Isolated clinical studies have found that one in two, not one in ten, individuals presenting with depressive disorders have features of bipolar spectrum disorders. If these 4.5.4 epidemiology of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 648
ﬁ gures are correct, then this would presumably lower the rates of 
major depression, but would correspondingly increase the rates of bipolar disorders.
Over the past decade, one of the controversial ﬁ  ndings in the 
epidemiology of major depression has been whether the rates of depression are increasing, and whether it is occurring at a younger age. Despite methodological concerns about the reliability of life-time major depression, studies across countries have reasonably consistently documented an increasing rate of major depression with an earlier age of onset.
(13) As mood disorders are the single 
largest risk factor for suicide, it is also of note that, in most Western countries, the rate of suicide, especially in young adults, increased considerably from the 1970s to 1990s, although the suicide rate is now declining in many countries. This could, however, reﬂ  ect better 
recognition and treatment of depression.

(a) Genetics
There is now substantial evidence that genetic factors are of major importance as risk factors for vulnerability to major depression. While traditional estimates have put the heritability at about 40 per cent, when Kendler et al.
(9) allowed for the moderate reliability of 
the diagnosis of major depression, the heritability estimate increased to 70 per cent. Of greater interest is that the genes for major depression do not appear to be unique for depression, but 
overlap with the genes for anxiety and the genes for neuroti cism.
(14, 15)
The greater prevalence of depression in women may be due to the 
strong association of anxiety and neuroticism with depression, and 
that the higher rates of anxiety and neuroticism in women lead to higher rates of depression.
(b) Gender
One of the most consistent ﬁ  ndings in the epidemiology of major

(b) Gender
One of the most consistent ﬁ  ndings in the epidemiology of major 
depression is that the ratio of women to men is approximately2:1. This increased rate of major depression in women arises during puberty, as in childhood there is a slightly higher prevalence of depression in boys than girls. The timing of this transitionin rates by gender is related to biological puberty rather than justto age.
(c) Childhood experiences
Early theorizing suggested that the loss of a parent in childhood increased the later risk for major depression; although many stud-ies have examined this issue, they have inconsistently found it to be a risk factor for adult depression. However, studies that examine the nature of child–parent attachment using a measure such as the Parental Bonding Instrument have consistently found that a lack of parental care is associated with increased rates of depression.
(16)

(16)
More recently, childhood sexual abuse has been established as a risk factor for adult major depression.
However, cumulative childhood disadvantage almost certainly 
poses a greater risk to later depression than any single childhood variable in isolation. Thus, if studies only look at single childhood r isk 
factors, they may miss the full impact of global childhood adversity. The converse of childhood risk factors is childhood resilience, and it is probable that one good relationship with an adult and high intelligence in the child may, in part, protect from other adversities.(d) Personality
There has been a long history of interest in the likelihood that people with certain personality traits are more vulnerable to depression than others. It is likely that those individuals who are unduly anxious, impulsive, and obsessional may have increased 
rates of later major depression. The best data exists for neuroti-

cism, which emerges as a clear risk factor for the later development of depressive and anxiety disorders. However, as already mentioned, the same genes seem to contribute to the development of neuroti-cism and to later anxiety and depressive disorders.
(e) Social environment
There has been considerable interest in the role of marital status as a risk factor for major depression. For men, it appears clear that married men have the lowest rate of depression, while separated or divorced men have the highest rates of major depression. In women, the association is slightly less clear, but in the ECA study the same ﬁ ndings applied for women as for men. Understanding the nature

of the association between marital status and rates of depression is more problematic. If personality is a risk factor for depression, then the same traits could interfere with the ability to marry or to stay married. There is little doubt that depression sometimes contrib-utes to marital maladjustment and separation or divorce. Finally, the stresses associated with divorce and separation could increase the likelihood of an episode of depression occurring.
In the classic and inﬂ  uential work of George Brown on working-
class women, having three or more children, a lack of paid employ-
ment, and the lack of a conﬁ  dent were risk factors for the development 
of an episode of depression. Subsequent studies have inconsistently replicated the risk factors of having children or lack of paid employ-ment, but have supported the ﬁ  nding that the lack of a conﬁ  dent 
increases the risk of depression.
It is well established that adverse life events, particularly those

It is well established that adverse life events, particularly those 
characterized by loss, increases the risk of an episode of major depression. Interestingly, however, the life events which may consti-tute the greatest risk may be ‘dependent’ rather than ‘independent’ life events. The increased vulnerability to an episode appears to last for a period of two to three months following such an event.
Early thinking about depression suggested that there would be 
those depressions that occurred for largely biological reasons and those precipitated by adverse life events; however, it is now clear that such a dichotomous view is incorrect. Kendler et al.
(17) showed 
that there is a signiﬁ  cant genotype by environment interaction in 
the prediction of onset of major depression. They proposed that genetic factors inﬂ  uence the risk of onset of depression, in part, by

the prediction of onset of major depression. They proposed that genetic factors inﬂ  uence the risk of onset of depression, in part, by 
increasing the sensitivity of individuals to the depression-inducing effects of stressful life events.
(f) Physical illness
Having a chronic or severe physical illness is associated with an increased risk for depression. The mechanisms behind this increased risk may vary depending upon the physical disorder. In disorders such as Parkinson’s disease, it is possible that there are shared neurotransmitter abnormalities between Parkinson’s disease and depression. In post-stroke depression, there is good evidence that the location of the lesion, at least in part, contrib-utes to the rate of depression, which suggests a neuroanatomical/neurotransmitter connection between the physical illness andthe likelihood of depression. For non-central nervous system

649
disorders, such as acute myocardial infarction, diabetes, and
cancers, the mechanism for this association is less clear. However, at least in the case of patients with cancer, most do not suffer from major depression and, if they do, the key risk factors are family history and a past history of depression. This suggests that the stress associated with a serious or chronic physical illness mayact by bringing out an individual’s lifetime vulnerability todepression.
An integrated aetiological model
The ultimate purpose of studying risk factors for depressive disorders is to contribute to the development of an integrated aetiological model. The most promising research in this area has been per-formed by Kendler and colleagues on twins from the Virginia Twin Register.
(18) In this study, both female–female and male–male twin

(18) In this study, both female–female and male–male twin 
pairs of known zygosity have been assessed on a series of occasions at longer than one-year intervals. A range of predictor variables; including genetic factors, parental warmth, childhood parental loss, childhood disorders, lifetime traumas, neuroticism, self esteem, social support, past depressive episodes, recent difﬁ  culties, and

recent stressful life events have been examined to see how they contributed prospectively to the development of an episode of major depression over the next 12 months. In considering the results from this study, it is important to bear in mind the limita-tions of this landmark study, especially the fact that they were predicting the onset of an episode over 12 months and not predict-ing lifetime episodes. However, despite these caveats, Kendler and colleagues developed a model that predicted over 50 per cent of the variance in the liability to develop major depression in the next twelve months. The strongest predictors to depression were as follows:
X stressful life events
X genetic factors
X previous history of major depression
X neuroticism
It is of note that some of the risk factors exerted these effects

It is of note that some of the risk factors exerted these effects 
directly, while other effects were largely indirect. Thus, 60 per cent of the effect of genetic factors on liability to depression was direct, but the remaining 40 per cent was indirect and largely mediated by past episodes of depression, stressful life events, and neuroticism. Variables such as perceived parental warmth had no direct effect on liability to develop an episode of major depression, but did impact upon neuroticism, a history of a past depressive episode, recent difﬁ  culties, and lifetime traumas.The most comparable

prospective studies looking at risk factors for the development of major depression have been undertaken during the postpartum period, which is a time of increased risk of depression. In thisspecial case, the most consistent risk factors are family historyand a past history of depression, and there is lesser support for a lack of social support, neuroticism, and complications during childbirth.
As one of the key tasks of epidemiology is to contribute to an 
understanding of aetiology, models that integrate risk factors are important strategies for further research. They provide clinicians 
with predictive power, and can also guide intervention studies to 
prevent the onset of episodes of depression.Comorbidity
One of the important contributions of epidemiology to the study of mood disorders over the past twenty ﬁ  ve years has been the

One of the important contributions of epidemiology to the study of mood disorders over the past twenty ﬁ  ve years has been the 
recognition of the extent to which depression and other psychiat-ric disorders are often comorbid. In both the ECA study and NCS, over two-thirds of all individuals identiﬁ  ed as having an 
episode of major depression also met the criteria for one or more other psychiatric disorders. Not surprisingly, the most common comorbid disorders are anxiety disorders and substance-abuse 
disorders. In the NCS, the anxiety disorders with the highest odds 
ratios indicating comorbidity were generalized anxiety disorder, panic disorder, and post-traumatic stress disorder. It is also important to note that for most anxiety disorders, with the excep-tion of panic disorder, the anxiety disorder usually predates the onset of the depressive disorder.
(19) This is of considerable impor-

tance, as the risk factors for pure major depression differed from the risk factors for comorbid major depression. Furthermore, the cohort effects of increasing rates of major depression were largely attributable to increasing rates of comorbid major depression, rather than to increasing rates of pure major depression. These results raise important issues for prevention, as it may wellbe that targeting young people with anxiety disorders and could be a major step to the prevention of the development of later major depressive disorders.
The second key area of comorbidity with major depression is 
with alcohol dependence. Data from the Virginia Twin Register suggest that part of this comorbidity is due to shared genetic factors, 
although there is also a smaller common environmental risk factor 
to both disorders.
Another area of considerable comorbidity with major depression

Another area of considerable comorbidity with major depression 
is the personality disorders. The comorbidity between major depression and these disorders is receiving considerable attention in clinical samples but, to date, there are only limited data inepidemiological samples on the importance of these patterns of comorbidity.
One of the major challenges for psychiatry presented by epidemio-logical studies of depression has been the consistent ﬁ  nding that 
the majority of cases of depression in the community are not recognized, diagnosed, nor treated. In the ECA study, it was found that 65 to 70 per cent of people with depression had visited a health professional in the last 6 months, but only 15 to 20 per cent had had a visit for a mental health reason and only about 10 per cent had seen a mental health specialist. Ormel et al.
(20) found that

(20) found that 
patients with depression who present with largely somatic rather than psychological symptoms are extremely unlikely to berecognized by general practitioners. Even if major depression isrecognized in the primary care setting, it is often not adequately treated.
(21)
 1. Murray, C.J.L. and Lopez, A.D. (1996). The global burden of disease and 
global health statistics . Harvard University Press, Boston, MA.
 2. Akiskal, H.S. (2003). Validating ‘hard’ and ‘soft’ phenotypes within 
the bipolar spectrum: Continuity or discontinuity? Journal of Affective 
Disorders ,73, 1–5.4.5.4 epidemiology of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 650
 3. Blacker, D. and Tsuang, M.T. (1992). Contested boundaries of bipolar 
disorder and the limits of categorical diagnosis in psychiatry. American 
Journal of Psychiatry, 149, 1473–83.
 4. Kessler, R.C., Rubinow, D.R., Holmes, C., et al. (1997). The 
epidemiology of DSM-III-R bipolar I disorder in a general population 
survey. Psychological Medicine, 27, 1079–89.
 5. Weissman, M.M., Bland, R.C., Canino, G.J., et al. (1996). Cross national 
epidemiology of major depression and bipolar disorder. Journal of the 
American Medical Association, 276, 293–9.
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and bipolar II disorder.  Journal of Affective Disorders, 50, 143–51.
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depression: an evaluation of DSM-IV criteria. American Journal of 
Psychiatry, 155, 172–7.
 8. Wainwright, N.W.J., Surtees, P .G., and Gilks, W.R. (1997). Diagnostic

 8. Wainwright, N.W.J., Surtees, P .G., and Gilks, W.R. (1997). Diagnostic 
boundaries, reasoning and depressive disorder, I. Development of a probabilistic morbidity model for public health psychiatry. 
Psychological Medicine ,27, 835–45.
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history of major depression in women. Reliability of diagnosis and heritability. Archives of General Psychiatry, 50, 863–70.
10. Sullivan, P .F., Prescott, C.A. and Kendler, K.S. (2002). The subtypes of 
major depression in a twin registry. Journal of Affective Disorders ,
68, 273–84.
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prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey. American 
Journal of Psychiatry, 151, 979–86.
12. Jenkins, R., Lewis, G., Bebbington, P ., et al. (1997). The National

12. Jenkins, R., Lewis, G., Bebbington, P ., et al. (1997). The National 
Psychiatric Morbidity Surveys of Great Britain—initial ﬁ  ndings from 
the household survey. Psychological Medicine ,27, 775–89.
13. Cross National Collaborative Group (1992). The changing rate of 
major depression. Cross national comparisons. Journal of the
American Medical Association, 268, 3098–105.
14. Kendler, K.S., Neale, M.C., Kessler, R.C., et al. (1992). Major
depression and generalized anxiety disorder. Same genes (partly) different environment. Archives of General Psychiatry ,49, 716–22.
15. Andrews, G., Stewart, G., Allen, R., et al. (1990). The genetics of six 
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and genetic liability to major depression: genetic control of exposure to the environment? Psychological Medicine
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18. Kendler, K.S., Gardner, C.O. and Prescott, C.A. (2002). T oward a 
comprehensive developmental model for major depression in women. American Journal of Psychiatry ,159, 1133–45.
19. Kessler, R.C., Nelson, C.B., McGonagle, K.A., et al. (1996). Comorbidity 
of DSM-III-R major depressive disorder in the general population: results from the US National Comorbidity Survey. British Journal of 
Psychiatry, 168, 17–30.
20. Ormel, J., Koeter, M.W.J., Van den Brink, W., et al. (1991). Recognition, 
management and course of anxiety and depression in general practice. Archives of General Psychiatry, 48, 700–6.

21. Schulberg, H., Block, H.R., Madonia, M.J., et al. (1996). Treating major 
depression in primary care practice, eight-month clinical outcomes. Archives of General Psychiatry, 53, 913–19.4.5.5 Genetic aetiology 
of mood disorders
Pierre Oswald, Daniel Souery, 
and Julien Mendlewicz
Advances towards the understanding of the etiological mechanisms 
involved in mood disorders provide interesting yet diverse hypoth-eses and promising models. In this context, molecular genetics has now been widely incorporated into genetic epidemiological research in psychiatry. Affective disorders and, in particular, bipo-
lar affective disorder (BPAD) have been examined in many molec-

ular genetic studies which have covered a large part of the genome, speciﬁ  c hypotheses such as mutations have also been studied. Most 
recent studies indicate that several chromosomal regions may be involved in the aetiology of BPAD. Other studies have reported the presence of anticipation in BPAD and in unipolar affective disorder (UPAD).
(1–3) In parallel to these new developments in molecular 
genetics, the classical genetic epidemiology, represented by twin, adoption and family studies, provided additional evidence in favour of the genetic hypothesis in mood disorders. Moreover, these methods have been improved through models to test the gene-environment interactions.
In addition to genetic approaches, psychiatric research has

In addition to genetic approaches, psychiatric research has 
focused on the role of psychosocial factors in the emergence of mood disorders. In this approach, psychosocial factors refer to the patient’s social life context as well as to personality dimensions. Abnormalities in the social behavior such as impairment in social relationships have been observed during episode of affective disor-ders, and implicated in the etiology of affective disorders. Further, gender and socio-economic status also emerged as having a possi-
ble impact on the development of affective disorders. Finally, the onset and outcome of affective disorders could also be explained by 
interactions between the social life context and the individual’s temperament and personality. The importance of temperament and personality characteristics in the etiology of depression has been emphasized in various theories, although disagreement exists with regard to terminology and the etiology.

While signiﬁ  cant advances have been done in these two major 
ﬁ elds of research, it appears that integrative models, taking into 
account the interactions between biological (genetic) factors and social (psychosocial environment) variables offer the most reliable way to approach the complex mechanisms involved in the etiology and outcome of mood disorders. This chapter will review some of the most promising genetic and psychosocial hypotheses in mood disorders that can be integrated in interactive models.
Genetic epidemiology of mood disorders
The various strategies available to investigate genetic risk factors in psychiatric disorders belong to the wider discipline of genetic epidemiology. This combines both epidemiological and genetic investigations and has the primary objective of identifying the genetic and non-genetic (environmental) causes of a disease. Genetic epidemiological data in affective disorders has come mostly

651
from family, twin, adoption and segregation (within families) 
studies. Family, twin and adoption studies are the mainstay in establishing the genetic basis of affective disorders. These methods ﬁ rstly demonstrated that genetic factors are involved in the aetiol-
ogy of these disorders.
(4) Twin and adoption data may also be 
used to investigate the relative contributions of genetic and envi-ronmental factors to the aetiology of a disease.
(5) The exact contri-
bution of these factors is not yet ﬁ  rmly understood for affective 
disorders but some studies provide contributing ﬁ  ndings. The 
study of adoptees who are separated from their biological parents has consistently favoured the gene-environment hypothesis in the aetiology of diverse psychiatric disorders.
(6) In adoption studies, 
both UPAD and BPAD have been described to be more frequent in biological relatives of the adopted subject, suffering from affective disorders than in adopted relatives.
(7)

(7)
The diagnostic validation and the structure of the genetic and 
environmental risk factors in mood disorders are also approached in twin studies.
(8) From the landmark study of 
Rosanoff et al . in 1934 to more recent works from Mc Guffin
et al .(9) and Kieseppa et al .,(10) concordance rates for BPAD
are higher in monozygotic twins (20–100 per cent) than in dizygotic twins (0–38 per cent).
Molecular genetics in affective disorders

The rapid advance in molecular genetic techniques over the last decade has generated a large database of DNA markers across the whole human genome and has enabled chromosomal regions throughout almost the entire genome to be studied in affective disorders. These studies have been performed mainly using linkage and association methodologies. Current linkage and association methods investigate heritable factors at a molecular genetic level, and enable genes to be mapped.
(11) These approaches are mostly 
applied to BPAD, which is considered to be the ‘core’ phenotype in affective disorders. Linkage analysis tests the hypothesis that a linkage relationship exists between a known genetic marker and a trait which is known to be genetically determined but has not yet been mapped on a chromosome.

(12) Two genetic loci are linked 
if they are located closely together on a chromosome. In linkage analysis, the distance between a marker locus and the gene under investigation is used for gene mapping. This method was originally designed to explore a major single genetic transmission and to evaluate the extent of co-segregation between genetic markers and the phenotype investigated in pedigrees. The major problems which linkage methodology face when applied to affective disorders are the complex aetiology and inheritance patterns. More than one locus are probably involved in susceptibility to these disorders, and the exact mode of transmission is not known. Mis-speciﬁ  cation of the 
genetic parameters of the phenotype may lead to errors in linkage studies.
(12) Furthermore, the linkage approach fails to detect minor 
gene effects which contribute to genetic susceptibility to the disor-der.
(13) More recently, genome-wide linkage studies have been per-

formed on samples of families with multiply affected members.(14)
The association method offers an alternative strategy of studying 
genetic factors involved in complex diseases in which the mode of transmission is not known.
(15) The association strategy does not 
require genetic parameters to be known (non-parametric method). The purpose of association studies is to compare frequencies of genetic marker alleles in patient and control populations in order to detect linkage disequilibrium. Linkage disequilibrium between 
the disease locus and the marker tested is deﬁ  ned as a level of

the disease locus and the marker tested is deﬁ  ned as a level of 
concordance between the two loci which is higher than would be expected by chance. The major reason for this is their proximity on a chromosome. The major advantage of association studies is that they can detect genes with minor effects other than a single major locus (SML). The major limitation of this approach is that spuri-ous associations between a genetic marker and a disorder may result from variations in allele frequency between cases and controls observed if the two populations are ethnically different (population stratification). It is important in this case tocompare populations which are homogenous in their ethnic background. A further major difﬁ  culty in association studies is 
the interpretation of the precise meaning of the association observed.
(16) The result may be interpreted as linkage disequilib-

rium between the disease locus and the associated marker allele(s). Alternatively, the associated marker may be interpreted as a susceptibility factor which is directly involved in the disease. The candidate gene approach in association studies is a useful method to investigate linkage between markers and diseases. A candidate gene refers to a region of the chromosome which is potentially implicated in the aetiology of the disorder concerned. The possibility of false positive results must be taken into account, as a very large number of candidate genes now exist. The proba-bility that each of these genes is involved in the aetiology of the disorder is relatively low.
Linkage studies in affective disorders 
(See(17) for review)
From more than two decades of linkage studies, it seems that several

From more than two decades of linkage studies, it seems that several 
chromosomal locations have been associated with affective disor-ders, sometimes with conﬂ  icting results. Mendlewicz et al
(18) ﬁ rst 
reported possible genetic linkage between manic depression and coagulation Factor IX (F9) at Xq27 in 11 pedigrees. Another region of interest seems to be the chromosome 18 where the pericentro-meric region was suggested to carry susceptibility genes. The chromosome 11 has been thoroughly investigated in AD but showed contradictory results. Chromosomes 4, 6, and 10 were also investigated with conﬂ  icting and/or unreplicated results. Darier’s

disease (keratosis follicularis), a rare autosomal dominant skin disorder associated with increased prevalence of epilepsy and mental retardation, whose gene was mapped on chromosome 12 (12q23–24.1), was found to cosegregate with BPAD in one pedigree. This result was replicated in several family studies. Genome-wide linkage analyses provide an accurate tool to study 
regions of interest. In BPAD, early positive and promising results 
were contradicted by further analyses. This fact is not surprising, since these studies were performed on small samples sizes, insufﬁ  -
cient to replicate modest linkage signals.
(19) Meta-analyses were 
thus performed on BPAD to increase the power to detect modest linkage signals.
(14) Bipolar loci with evidence of linkage were 
found on the following arms: 4p, 6p, 6q, 9p, 10q, 12q, 13 q, 14q, 17q, 18p–q, 21q, 22q.
(14,20)  McQueen et al.(21) found susceptibility

(14,20)  McQueen et al.(21) found susceptibility 
loci on chromosomes 6q and 8q by using a combined analysis of eleven linkage studies. A recent study from Schumacher et al.,
(22)
in four European samples, conﬁ  rmed previously reported loci, 
4q31 and 6q24, and provided evidence for a new linkage locus, 1p35-36.4.5.5 genetic aetiology of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 652
Candidate genes in affective disorders
Serotonin markers
Dysfunction of the serotoninergic system has long been suspected 
in major depression and related disorders. Depression can success-fully be treated with selective drugs which target serotonin receptors. The serotonin transporter may also be involved in susceptibility to affective disorders and in the response to treatment with these drugs. Most recent replication studies did not support these initial positive ﬁ  ndings. This has been the case for 5HTT.
(17) The trypto-
phan hydroxylase (TPH1) gene, which codes for the rate limiting enzyme of serotonin metabolism, is also an important candidate gene for affective disorders and suicidal behavior. Bellivier et al
(23)
reported a signiﬁ  cant association between genotypes at this marker

(23)
reported a signiﬁ  cant association between genotypes at this marker 
and BPAD, no association was found with suicidal behaviour. In a previous study in depressed patients suicidal behaviour has been associated with one variant of this gene.
(24) The tryptophan 
hydroxylase isoform (TPH2) showed an association between BPAD and suicidality.
(25)
Other candidate genes
Among other pathways, DRD2, DRD3, DRD4 and DAT1 were largely studied and replicated. Unfortunately, results remain con-ﬂ icting. Recent studies have implicated neurotrophic factors in the 
underlying disease processes of affective disorders. Brain-derived neurotrophic factor (BDNF), the most abundant of the neuro-trophins in the brain, enhances the growth and maintenance of several neuronal systems, serves as a neurotransmitter modulator, and participates in plasticity mechanisms such as long-term poten-tiation and learning.
(26) Although promising, BDNF did not

(26) Although promising, BDNF did not 
conﬁ  rm its role in the pathophysiology of affective disorders.(27,28)
Several new candidate genes from the well-known molecular 
cascades have been tested: PIK3C3 in the intracellular signalling pathway; PCDH11Y, a proto-cadherin and GSK3 β, a target  mole cule
of lithium. Finally, studies of circadian rhythm-related genes showed promising results in BPAD, such as ARNTL.
(29,30)
Anticipation and expanded trinucleotide 
repeat sequences
Anticipation implies that a disease occurs at a progressively earlier 
age of onset and with increased severity in successive generations. This may explain the non-Mendelian pattern of inheritance observed in some inherited diseases. Anticipation has been found to correlate with speciﬁ  c mutations in these syndromes: expanded 
trinucleotide repeat sequences. An expanded repeat sequence is unstable and may increase in size between family members, leading to increased disease severity of the disorder.

Anticipation has been described in BPAD and in UPAD.
(1,3) One 
study highlighted an association between Cysteine-Alanine-Glycine (CAG) trinucleotide repeats and BPAD illness in Swedish and Belgian patients with affective disorder.
(31) CAG repeats have been 
detected by the Repeat Expansion Detection method (RED-method). This hypothesis has also been tested in a family sample of two-generation pairs with BPAD.
(32) A signiﬁ  cant increase in CAG 
repeats between parents and offspring generations was observed however, when the phenotype increased in severity, i.e. changed from major depression, single episode or unipolar recurrent depression to BPAD. This is the ﬁ  rst evidence of genetic anticipa-
tion in BPAD families and should be followed by the identiﬁ  cation

tion in BPAD families and should be followed by the identiﬁ  cation 
of loci within the genome containing triplet repeats. CTG 18.1 on chromosome 18q21.1 and ERDA 1 on chromosome 17q21.3 are two repeat loci recently identiﬁ  ed but were not found to be associ-
ated with BPAD.
(33) A newly identiﬁ  ed CTG/CAG repeat was found 
to be associated with BPAD.(34)
Phenotype deﬁ  nition
Facing the heterogeneity of results, it has been hypothesized that 
genetic factors could explain some symptoms or clinical features of the syndromes, such as severity of the disease, age at onset or gender predominance. Early-onset, and more speciﬁ  cally pediatric-
onset, BD has been suggested to have its own pattern of genetic susceptibility factors. Family studies have consistently found a higher rate of BD among the relatives of early-onset BD patients than in relatives of later-onset cases.
(35) Among the most recent 
studies, Faraone et al.(36) found, in a genome-wide scan, 3 regions

studies, Faraone et al.(36) found, in a genome-wide scan, 3 regions 
of interest that may inﬂ  uence age at onset of mania in BPAD. Geller 
et al.(37) found an association between BDNF and BPAD with early-
onset. Massat et al .(38) provided evidence for the inﬂ  uence of 
HTR2C in early-onset BPAD
More speciﬁ  c neurophysiologic, neuroimaging, neurocognitive, 
or neurochemical trait measures might identify homogeneous groups of patients. These ‘traits’ are called ‘endophenotypes’ and are believed to represent the genetic liability of the disorder among non-affected subjects.
(39) Endophenotypes in BD are difﬁ  cult to 
deﬁ ne. Circadian rythms, stress reactivity and appetite regulation 
have been proposed. Bipolar patients are also suggested to show inappropriate emotional responsiveness. Using emotional facial stimuli, depressed BD patients show impaired recognition ofhappy and sad facial expressions.
(40) These ﬁ  ndings conﬁ  rm a

particular pattern of characteristics in BD, and suggest that genetic factors may explain these characteristics, rather than the wholeclinical picture.
Shared genetic predisposition between BPAD and 
If BPAD and schizophrenia (SCZ) are distinguishable, they may 
share some characteristics. Indeed, family studies show partial overlap in familial susceptibility for these two conditions.
(41)
Evidence for linkage of both BPAD and SCZ were found on 18p11, 13q32, 10p14, 22q11–13 and 6p22.2.
(42–44)  More interestingly, two 
genes showed promising results in molecular genetic studies in 
these two conditions. From the ﬁ  rst report from Hattori et al.,(45)
G72, found on 13q34 and encoding d-amino acide oxidase activa-
tor (DAOA), was found to be associated with delusion or psychosis, 
rather than with the entire bipolar or schizophrenic clinical pictures.
(46) Although robust, these results were conﬁ  rmed in a

(46) Although robust, these results were conﬁ  rmed in a 
recent meta-analysis from Detera-Wadleigh et al .(47) Largely
distributed in neurones, DISC1 (Disrupted in Schizophrenia 1) 
interacts with many proteins and is related to several neuronal functions. Thomson et al.
(48) found a robust association between 
DISC1 and BPAD, but this result needs conﬁ  rmation. Theses cases 
of shared genetic predisposition emphasizes the need, in future classiﬁ  cation systems such as DSM-V , to focus on classiﬁ  cation 
that may more closely represent expression of underlying biologic systems.
(49)

653
Pharmacogenetics
One of the main difﬁ  culties in clinical practice is the inability to 
know a priori  which psychotropic drug will be best suited for each 
case. Therefore, several groups worldwide try to overcome that obstacle by searching genetic markers that might be predictive of treatment response.
BPAD
The ﬁ  rst studies on the relationship between response to lithium 
and family history have been published in the 1970s, supporting an association between a family history of BPAD and satisfactory response to treatment. Mendlewicz et al.
(50) ﬁ rst reported a study 
of 36 patients through a double blind study of lithium prophylaxis. They found that 66 per cent of the responders to lithium had at least one ﬁ  rst-degree relative with BPAD, and that only 2–1 per cent 
of the lithium nonresponders had a ﬁ  rst-degree relative with BPAD. 
Lipp et al.
(51) ﬁ rst reported an association between DRD2 and non-
response to lithium. Several studies have followed (See(52) for

Lipp et al.
response to lithium. Several studies have followed (See(52) for 
review). Positive results were found in TPH and 5HTT.(53,54)
UPAD
Previous studies of an association between poor antidepressant response in depressive patients and 5HTT were largely replicated and could be considered as a robust ﬁ  nding (see
(55) for exhaustive 
review and discussion). Among more recent ﬁ  ndings, GNB3 (beta3 
subunit of G protein) and DAT1 were found to be associated with treatment response. Binder et al.
(56) found an association between

(56) found an association between 
FKBP5, which plays an important role in the glucocorticoid recep-tor function, and rapid response to antidepressant. Interestingly, this group of patients was characterized by a high rate of relapses. Finally, the large STAR*D (Sequenced Treatment Alternatives to Relieve Depression) project provided recent promising data for HTR2A 5HTT and GRIK4, which codes for the kainic acid-type glutamate receptor KA1 and treatment response.
(57–59)
Psychosocial factors in affective disorders

(57–59)
Impairment in social relationships, dysfunctional cognition, gender, economic status, and temperament has been suggested as involved in the emergence of mood disorders. However, empirical studies on psychosocial factors of patients with affective disorders examine psychosocial features assessed after recovery from or/and at the time of episodes of affective disorders. These retrospective studies might not be able to distinguish between premorbid psychosocial patterns and those which result from previous episodes of illness. Further, longitudinal studies focusing on the role of psychosociological factors have involved predictions of recurrence or exacerbation of symptomatology in previously affected people, but not regarding the onset of the diseases. Thus, the demonstration of temporal antecedence to the initial onset of affective disorder is extremely difﬁ  cult.
(60) Thus, the conclusions in

(60) Thus, the conclusions in 
terms of etiological psychosocial factor are limited.
Impairment in social and familial 
relationships
Difficulties in social functioning are concomitant to depressive
disorders.(61) The concept of social support has been widely used to predict general health and more specifically psychiatric
symptoms.(62) Previous research revealed that the degree of integra-
tion in a social network, or structural support, have a direct positive effect on well-being, reducing negative outcomes in both highand low stress life events. Among depressed individuals, dysfunc-tion in social activities has been found to persist long timeafter remission from the depressive episode.
(63) The social dysfunc-
tioning concerns more speciﬁ  cally marital relationships, parental, 
and familial relationships.
The relationship between marital disturbance and affective dis-

orders has received increased attention over the past decades. First, descriptive studies have suggested that marital conﬂ  ict correlates 
highly with concomitant depression,
(64) and marital therapy has 
been found to be effective in reducing the symptoms of depression, alone as well as in combination with pharmacotherapy. Further, previous research found dysfunctional patterns of communication in couples with a depressed spouse.
(65, 66) The lack of a conﬁ  ding 
and intimate relationship leaves individuals vulnerable to depression.
(67, 68)  Finally, marital distress may also exacerbate 
difﬁ culties experienced in extramarital relationships,(69) thereby

difﬁ culties experienced in extramarital relationships,(69) thereby 
increasing introverted behavior and social isolation. In similar manner, the absence of a marital partner may hasten the onset of depression among vulnerable individuals.
(70)
The parental relationships seem also to have a great impact in the 
course of affective disorders. A variety of authors have emphasized the importance of the quality of early experiences with parents in the development of adult depression. Beck ﬁ  rst, explicitly attributes 
the development of negative cognition and negative schemata of self to critical, disapproving parents.
(71)
Dysfunctional cognition
According to the helplessness model of depression(73) vulnerability

(71)
According to the helplessness model of depression(73) vulnerability 
to depression derives from a habitual style of explaining the causes of life events, known as attributional style. A large body of research found that individuals suffering of depression think more negatively than healthy individuals. Speciﬁ  cally, depressed patients have a 
tendency to make internal, stable, and global causal attributions for negative events, and to a lesser extent, the attribution of positive outcomes to external, speciﬁ  c, and unstable causes. In other words, 
depressed patients have a low self-esteem.
(74,75)  Thus, when think-
ing about the self, past, current and future circumstances, depressed patients emphasize the negative, and this process is likely to con-tribute to the perpetuation of their depressed mood.
Gender

Gender
Evidence for sex differences in responses to depression comes from a large number of studies. Women are consistently reported to have greater prevalence of affective disorders than men.
(76,77)  First, 
women may experience two important periods, known to be asso-ciated with higher rates of depression: pregnancy and post-partum. The prevalence of major or minor depression among pregnant women ranges from 7 per cent to 26 per cent.
(78) Depression dur-
ing pregnancy is a strong predictor of postpartum depression. The prevalence of postpartum depression ranges from 10 per cent to 15 per cent in the ﬁ  rst year after childbirth.
(79) Besides these two 
speciﬁ  c conditions, the reasons for this sex difference are unclear,

speciﬁ  c conditions, the reasons for this sex difference are unclear, 
and are as likely to be social as biological.4.5.5 genetic aetiology of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 654
Divergences in the number and quality of social and occupational 
roles have been proposed to explain the greater prevalence of affective disorders among women. In the context of marital rela-tionship, previous research has indicated that for men, marriage confers a protection against illness, while it appears to be associated with higher rates of depression for women.
(80) There has been 
some evidence that within the marriage the traditional female role is limiting, restricting, which may lead to depression.
(81,82) For 
example, the role of child caretaker has consistently been shown to be associated with both high levels of stress and a higher incidence of depression for women.
(83)Women are found to have more 
depressive symptoms when there are young children in the home, and this tends to increase in an almost linear fashion according to the number of children in the household.
(84) Further, since women

(84) Further, since women 
who are employed outside the home also tend to be responsible for household chores,
(85) the notion that differentiation in occupa-
tional roles could partially explain the prevalence of depression for women is supported.
Socio-economic status
Many studies have reported that low socio-economic status is associated with high prevalence of mood disorders.
(86) Since a long 
time, in social psychiatry, the ‘social causation’ and ‘social selection’ hypotheses have been formulated to explain the role of the low socio-economic status in the disease. The causation hypothesis suggests that the stress associated with low social position, that is exposure to adversity and lack of resource to cope with difﬁ  culty, 
may contribute to the development of the affective disorder
(87)

(87)
while the social selection hypothesis argued that genetically predis-posed persons drift down to or fail to rise out of such positions.
(88,89)
Thus, the social selection hypothesis emphasizes the genetic inter-pretation of cause, while social causation hypothesis focuses on the etiologic role of the environment. Few longitudinal data sets are available to test the causal hypothesis. Nevertheless, there is evidence that disadvantaged socio-economic status, poverty, or education and occupation can be considered as risk factors for mood disorders.
(90,91) Nevertheless, Bruce and Hoff found that the 
effect of poverty is substantially reduced when controlling for degree of isolation from friends and family, suggesting that social isolation mediates some of the relationships between economic status and mood disorders.
(92)
In summary, a positive relationship has been found between

(92)
In summary, a positive relationship has been found between 
socio-economic status and vulnerability to affective disorders, with higher rates of vulnerability found among individuals with lower educational and social achievement levels.
Temperament and behaviour
T emperament has been deﬁ  ned in terms of differences in the 
adaptative systems, that is differences in reactivity and self-regula-tion to the social context.
(93–95)
The model of temperament developed by Eysenck approaches 
temperament in terms of cortical arousal.(96) Eysenck suggested 
that individuals differ in their basic arousability and therefore, in their optimal level of stimulation. These physiological differences give rise to the primary personality dimension of introversion-extraversion. Introverts are said to possess relatively reactive reticu-lar systems, and thus to attain their optimal level of cortical arousal at relatively low level of stimulation. As a result of their low optimal

arousal level, introverts are expected to prefer and seek out mild forms of stimulation and to avoid more intense and novel forms of stimulation. In contrast, extraverts are said to possess relatively unreactive reticular systems, to have correspondingly high optimal levels of cortical arousal, and to therefore, approach more intense and novel forms of stimulation.
The differences between the Cloninger’s model and other models 
are that Cloninger assumes relationships between biogenic amine neurotransmitters (norepinephrine, serotonin, and dopamine) and personality dimensions. Speciﬁ  cally, Cloninger deﬁ  ned tempera-
ment dimensions in terms of individuals’ differences in associative learning in response to novelty, danger or punishment, and reward. Further, he hypothesized a positive correlation between serotonin-ergic activity and harm avoidance, dopaminergic activity and nov-
elty seeking, and ﬁ  nally between noradrenergic activity and reward

elty seeking, and ﬁ  nally between noradrenergic activity and reward 
dependence. According to this author, these aspects of personality denote traits that are usually considered temperament factors because they are heritable, manifest early in life, and apparently involved in learning. The possible tridimensional combinations of extreme (high or low) variants on these basic stimulus response characteristics correspond closely to the traditional descriptions of personality disorders. The speciﬁ  c relationship between tempera-
ment and mood disorder is not yet understood satisfactorily. Studies have been done regarding the Tridimensional Personality Questionaire (TPQ) scores in relation to mood disorder, the data available suggest that depressed patients have elevated harm avoid-ance scores.
(97–100)
The possible role of candidate genes has been investigated in per-

(97–100)
sonality. Association between a personality trait (Novelty Seeking) and the 7 repeat allele in the locus for Dopamine receptor D4 gene (DRD4) has been observed in a group of 124 unrelated Israeli normal subjects.
(101) Novelty Seeking was assessed from the 
Tridimensional Personality Questionnaire (TPQ).(102) An associa-
tion was also observed between similar personality traits and long alleles of DRD4 gene in 315 subjects, mostly male siblings from United States.
(103) This last study utilized the NEO Personality 
Inventory (NEO-PI-R)(104) from which TPQ Novelty-Seeking 
scores can be estimated. More recent studies also suggest a pattern of inﬂ uence on temperamental dimension exerted by serotonergic 
and dopaminergic genes.
(105) They studies, even not deﬁ  nitive, 
suggest that the contribution of these polymorphisms to the 
clinical presentation of mood disorders could be mediated by an

clinical presentation of mood disorders could be mediated by an 
inﬂ uence on personality differences.
The gene-environment hypothesis
The availability of molecular genetic ﬁ  ndings in affective disorders 
offers new directions in this research ﬁ  eld. It is now possible to 
consider the gene-environment hypotheses using the DNA as the genetic liability variable. In primate models, early experiences of 
maternal separation were found to confer increased risk of depres-
sion during adult age.
(106) Barr et al . found that infant rhesus 
monkeys showing a speciﬁ  c polymorphism in 5HTT were more 
likely to engage in rough play than were individuals without
this polymorphism.(107) In humans, a landmark study demonstrat-
ed that a functional polymorphism in the promoter region of 5HTT gene moderated the inﬂ  uence of stressful life events on

ed that a functional polymorphism in the promoter region of 5HTT gene moderated the inﬂ  uence of stressful life events on 
depression and suicidal behaviour.
(108) This study was replicated

655
with conﬂ  icting results using different methodologies.(109–112)
However, these results support the notion that a combination of 
genetic predisposition and speciﬁ  c life events may interact to facili-
tate the development of affective disorders.
The complexity and heterogeneity of affective disorders is a major limitation for gene-environment studies.This could be attributed to their non-Mendelian mode of inheritance. BPAD and UPAD are, in fact, phenotypes which do not appear to exhibit classic Mendelian recessive or dominant inheritance involving a single major locus. The presence of both environmental as well as genetic factors and phenotypic diversity also represent important problems when dealing with these diseases. After the era of enthusiasm due to ﬁ  rst 
results from linkage and association studies, the lack of replication and the identiﬁ  cation of potential methodological biases led to

results from linkage and association studies, the lack of replication and the identiﬁ  cation of potential methodological biases led to 
a period of pessimism. However, recent technological advances allow for the analysis of hundreds of components in a biological system simultaneously. Gene expression micro-arrays may analyse 
the expression of hundreds of genes in a speciﬁ  c tissue. More 
speciﬁ  cally, micro-array technologies measure levels of messenger 
ribonucleic acid (mRNA), an intermediate product between gene and protein.
(113) The levels of these ‘transcripts’ are compared 
between a population suffering from a speciﬁ  c disease and control 
subjects. The analysis of mRNA transcripts, instead of DNA regions, may provide additional information on genetic regulation processes of illness. Ultimately, the understanding of neurobiological pro-cesses underlying affective disorders may help developing therapeutic and prevention strategies.

Serretti, A. and Mandelli, L. (2008). The genetics of bipolar disorder: 
genome ‘hot regions’ , genes, new potential candidates and future directions. Mol Psychiatry ,13, 742–71
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4.5.6 Neurobiological aetiology 
Neurobiology provides an explanation of behaviour or experience

Neurobiology provides an explanation of behaviour or experience 
at the level, either of systems of neurones or individual cells. The current era of progress is driven by contemporary cognitive neuro-science and a rapid evolution in the platform technologies of imaging and genetics. These will allow us to improve our accounts of the functional anatomy of the component elements of mood and its disorder, their functional neurochemistry and, in all proba-bility, give meaning to what a cellular account of depressive illness may eventually describe. This chapter will offer a partial and per-sonal view of these developments to date.
There are now authoritative models of causation in mood disor-

der, established from well designed, large-scale twin studies (see Chapter 4.5.5). These inform the classical formulation of mood disorder as requiring a vulnerability, a precipitating factor or factors, 
and maintaining factors which prevent spontaneous recovery. 
Neurobiology will be addressed under these headings.
Vulnerability to mood disorder
The key vulnerability factors appear to be genes, temperament (also in substantial part genetic), and early adversity. There has been limited work on the neurobiology of these risk factors, as opposed to the vast effort to understand the depressed phenotype. However, for potential prevention either of onset or relapse, such factors appear more logical targets for current research effort and will be covered ﬁ  rst. Success in depression would parallel that seen

in moving the management of heart disease from the acute episode of infarction to the treatment of metabolic risk factors.
Neurobiology has informed the genetic search for candidate genes, starting with the human serotonin transporter (SERT) gene (see Chapter 4.5.5). There has been a terriﬁ  c proliferation of possible 
genetic effects deriving from neurobiological theories designed either to explain elements of the actions of psychotropic drugs, the depressed phenotype or from animal experiments. The latter are limited by the validity of animal models of depression per se. Some of the former will be noticed below.
Genes making small contributions to the risk of psychiatric dis-
order are emerging from direct analysis of the genome (see Chapter 2.4.2). Consistent ﬁ  ndings must inform biological investigations in

order are emerging from direct analysis of the genome (see Chapter 2.4.2). Consistent ﬁ  ndings must inform biological investigations in 
future. At this point it is uncertain whether insights will come from studying variation in individual genes, as has often been assumed, or from a much more complex understanding of cellular function regulated only in part by genetic variation. On the latter assump-tion the role of genetic hits is to direct attention to processes which may go wrong in the relevant disease. For mood disorder, these seem likely to be developmental or related to stress regulation.
(b) Temperament
The way in which genes may regulate the expression of vulnerability 
traits is suggested by animal studies. For example, when animals are selected for differences in emotional behaviour they also show different hypothalamic–pituitary–adrenal (HPA) axis function. Speciﬁ  cally, Roman high- and low-avoidance rats differentially

acquire a two-way active avoidance response in a shuttle box. High-avoidance animals show greater prolactin and HPA axis responsivity to stress compared with low-avoidance animals. However, young Roman strain rats show identical HPA axis reac-tivity, although prolactin responses and behaviour are different.
(1)
In other words, reactivity to the environment may share a measure of common genetic control across physiological and behavioural domains, but HPA abnormality per se develops secondary to emotional experience, or at least is magniﬁ  ed by it.
In human studies, neuroticism is an old psychological construct 
often criticized as reﬂ  ecting an average or habitual mood state

often criticized as reﬂ  ecting an average or habitual mood state 
rather than a truly independent risk. We have studied extremes of the dimension (high and low N) in young subjects before the onset of depression and in older groups who may or may not have expe-rienced depressive episodes. Interestingly, high neuroticism with or without a history of depression is associated with increased awakening cortisol
(2) in mature subjects, but not in subjects under 
20 years of age, echoing the rodent ﬁ  nding. Thus, N has a purely 
biological consequence that develops with emotional experience, but is independent of depression per se.
What the neuroticism construct has also lacked hitherto has

What the neuroticism construct has also lacked hitherto has 
been a plausible psychological dimension. Cognitive bias relevant to the onset of depression can be detected in young high N subjects. In emotional categorization and memory tasks, high N volunteers were faster to classify dislikeable self-referent personality character-istics and produced fewer positive memory intrusions. They also had a higher threshold for identifying happy faces. This suggests the hypothesis that risk for depression is largely manifest as reduced positive processing of emotional information
(3); increased negative 
processing appears to develop only after the actual experience of 
depression. Neural biases underlying this behaviour are even more readily detected.
(4) Our hypothesis is that high neuroticism is not 
just an habitual low mood but is biologically  founded in negative

just an habitual low mood but is biologically  founded in negative 
biases in attention, processing, and memory for emotional material. 
Indeed, there is now genetic evidence favouring a common genetic 
locus in human beings and rodent.(5) How emotional bias trans-
lates into either low-level symptoms or a full mood episode will 
be of great interest. Furthermore, depressive episodes per se appear to have an impact on brain function, and increase the risk of 
further relapse (see below).
(c) Early adverse experience
Adverse childhood experience was identiﬁ  ed in genetically uncon-
trolled studies as a risk factor predisposing women to subsequent

659
depression (Chapter 4.5.5) and has been conﬁ  rmed in genetically 
informative designs.(6) In a clinical context, such developmental or 
social effects are usually viewed as separable from biology. Indeed, their very existence is usually taken to validate a ‘social’ approach to psychiatry. From a more uniﬁ  ed point of view, however, one would 
predict measurable neurobiological consequences. In fact, such effects have proved to be more profound than most biologists anticipated.
Variations in maternal care produce individual differences 
in neuroendocrine responses to stress in rats. The offspring of mothers that exhibited more licking and grooming of pups during the ﬁ  rst 10 days after birth showed, in adult life, reduced plasma 
ACTH and corticosterone responses to acute stress.
(7) In addition, 
there was increased hippocampal glucocorticoid-receptor messen-ger RNA ( mRNA ) expression, enhanced glucocorticoid feedback

there was increased hippocampal glucocorticoid-receptor messen-ger RNA ( mRNA ) expression, enhanced glucocorticoid feedback 
sensitivity, and decreased levels of hypothalamic corticotrophin-releasing hormone ( CRH ) mRNA. Greater early maternal attention 
also substantially reduced subsequent behavioural fearfulness in response to novelty, increased benzodiazepine receptor density in the amygdala and locus coeruleus, increased α
2-adrenoreceptor 
density in the locus coeruleus, and decreased CRH receptor density in the locus coeruleus. Thus, maternal care serves to programme behavioural responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.
When BALB/cByJ mice were raised by an attentive C57BL/6ByJ

When BALB/cByJ mice were raised by an attentive C57BL/6ByJ 
dam, their excessive stress-elicited HPA activity was reduced, as were their behavioural impairments. However, cross-fostering the more resilient C57BL/6ByJ mice to an inattentive BALB/cByJ dam failed to elicit behavioural disturbances. In other words, vulnerable offspring may have their problems exacerbated by maternal behav-iour, while early-life manipulations may have less obvious effects in relatively hardy animals.
(8) Whether separation or stress paradigms 
in rodents can be taken as precise models of the mechanisms underlying the risk of mood disorder or other psychiatric problems cannot yet be decided, but their general relevance to the human case seems obvious. At present, data in human subjects is limited but ﬁ  ndings that relate to the better characterized animal models 
are emerging.
(9)
In fact, epidemiological data have linked increased risks of

(9)
In fact, epidemiological data have linked increased risks of 
cardiovascular, metabolic, neuroendocrine, and psychiatricdisorders in adulthood with an adverse foetal  environment as
well. Glucocorticoid excess may be the mechanism.
(10) Low-birth-
weight babies have higher plasma cortisol levels throughoutadult life, which suggests a permanent change in HPA function. Whether such effects and later effects of environmental stressin childhood can in part mediate co-morbidity between a rangeof psychiatric and physical disorders is of growing contemporary interest. It is unclear how, over- or underactivity in stress regula-tion contributes to psychiatric disorder: both appear to be impli-cated since awakening cortisol responses may be blunted insubjects with early adversity
(9) or enhanced in at risk neurotic
individuals.
Gene–environment interaction is the likely basis of the neurobi-

ology of mood disorder. In general terms this must be correct. Either the genetic/biological or the environmental factors could be targets for prevention. Whether the genetic mechanisms can be brought into sufﬁ  cient focus to allow speciﬁ  c new pathways to be 
identiﬁ  ed remains the major current challenge. It is often assumed 
that mediating characteristics or the endophenotype may have a simpler genetic architecture than the disease itself: unfortunately, 
the evidence so far gives reason for caution. This debate is currently very polarized between optimists (see Chapter 2.5.3 by Meyer-Lindenberg & Goldberg) and pessimists (see Chapter 2.4.2 by Flint). The genetic and developmental routes into distal common 
pathways regulating stress responses may be very numerous.

pathways regulating stress responses may be very numerous. 
Disorders that are both common and very variable in expression, such as depression, may turn out to have little speciﬁ  city that is 
worth talking about. Every illness may be an ensemble of many speciﬁ  c factors, none of which is individually going to lead to a 
more focused treatment or a better prediction of treatment response.
Precipitating factors: the neurobiology of life events
Like early adversity, the role of life events in depression has been afﬁ rmed in genetically controlled studies. Life events are relevant to 
almost all ﬁ  rst episodes of depression, but are less signiﬁ  cant in its 
recurrence. The biology of life events is subsumed in the biology of stress, at best a clumsy term. In human studies it will be always difﬁ cult to isolate the critical ingredients of a particular psychologi-

cal stress from the individual differences that stressed individuals bring to their experience. There have been few recent contributions to the ﬁ  eld of direct relevance to depression.
(11) However, a key 
clinical feature of the illness course in depression is the association of life events most strongly with ﬁ  rst episodes of depression. 
Subsequent episodes appear to need a less substantial environmen-tal trigger, as if the patient becomes sensitized.
(12) Patients with a 
strong family history may effectively be presensitized. Accordingly the effect of life events and the brain changes that occur with repeated or chronic illness is of great relevance to prevention and reduction of the risk of future episodes.
Maintaining factors: biological studies of the 
depressed state
In the majority of biological studies of affective disorder, patients

In the majority of biological studies of affective disorder, patients 
have been studied when ill and compared with normal controls. Over the years, this kind of design has produced a range of positive ﬁ ndings, usually of modest effect. It remains true to say that no 
biological changes have ever been found that distinguish between depressed patients and controls better than does the clinical assess-ment of the patients. What is also curious, and not a little tantaliz-ing, is the impression that some symptoms may, in part, represent biological adaptations directed to put things right. Thus, on the one hand, there may be consistent effects upon hormone secretion 
or sleep that represent phenomena of illness. On the other, deliber-
ate changes in hormone status or sleep deprivation may modify the 
state of depression. Depression is also so common in its less

state of depression. Depression is also so common in its less 
severe forms, that it is tempting to see it as a biologically adaptive mechanism in response to loss or social defeat. Informative animal 
analogues might be expected to exist, but theoretical comparisons 
with other biological models such as early separation in primates 
or hibernation in bears are limited by the species gap.
(13)
However, what makes depression the clinical burden it is, remains

(13)
However, what makes depression the clinical burden it is, remains 
its tendency to persist and sometimes become chronic. The bio-logical factors contributing to this are still poorly understood, but they would provide an obvious target for novel drug development. In general it is not yet obvious which symptoms of acute depres-sion are related to this key biology and which are either irrelevant or even adaptive. If there is now a consistent interest, it has been 4.5.6 neurobiological aetiology of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 660
stimulated by the gradual acceptance that some cells divide to pro-
duce neurones in the mature brain, especially in the hippocampus. It is very tempting to suppose that the plastic effects maintaining the unwanted brain state in depression may be related to neurogen-esis or its failure, which is a beautiful hypothesis requiring conﬁ  r-
mation by direct evidence.
(a) The depressed state: functional anatomy
Perfusion or metabolic imaging can indirectly detect changesin neuronal activity (see Chapters 2.3.6 and 2.3.8). Signals can be well localized, but their meaning is ambiguous. They may reﬂ  ect

Perfusion or metabolic imaging can indirectly detect changesin neuronal activity (see Chapters 2.3.6 and 2.3.8). Signals can be well localized, but their meaning is ambiguous. They may reﬂ  ect 
either reversible changes in function or a semi-permanent loss of neuronal connectivity. Reductions in function in anterior brain structures have been typical in major depression. Hypoperfusion tends to be greatest in frontal, temporal, and parietal areas and most extensive in older patients; high Hamilton scores tend to be associated with reduced perfusion.
(14) Reductions in frontal areas

(14) Reductions in frontal areas 
may be more likely in patients with impoverished mental states. Thus, neuropsychological testing in major depression shows evi-dence of slowing in motor and cognitive domains, with additional prominent effects on mnemonic function that are most marked in the elderly. These effects are correlated with reduced frontal perfu-sion in the elderly. In younger patients, there may actually be increased perfusion in the frontal and cingulate cortex. Metabolic increases in the cingulate gyrus have been associated with a good 
treatment response.
(15) Highly localizing ﬁ  ndings have been unusual, 
however. The only exceptions have been within-subject changes on recovery in the mesial frontal cortex and perhaps the basal ganglia.
(14)
There has been a dramatic expansion of imaging studies of

(14)
There has been a dramatic expansion of imaging studies of 
emotional processing in normal volunteers, now usually with fMRI (see Chapters 2.3.8 and 2.5.4). It is well summarized by meta-analysis of over 300 such emotion induction and cognitive task. Emotion induction resulted in inferior medial activation and cognitive tasks resulted in dorsolateral activation.
(16) However, the 
broad spread of precise loci of activation means that localization within the frontal lobes has proceeded little further. It may explain the diffuse reports typical of the depression literature. Nevertheless, a focus on limbic activity has led to quite specific, quasi-neurological hypotheses about connectivity in frontal areas andto treatment innovation: deep brain stimulation adjacent to sub-genual cingulated cortex (Brodmann area 25).
(17) How effective,

(17) How effective, 
and how localized this treatment effect really is, will be an impor-tant challenge to the ﬁ  eld. However, it underlines that ‘functional 
imaging’ of brain perfusion primarily informs anatomy.
Isotope-based imaging of receptor occupation could more 
plausibly offer mechanistic understanding of psychiatric disorder. In depression, it has progressed with the availability of suitably informative ligands. However, the ﬁ  eld generally tends to employ 
small sample sizes, and fundamental advances are difﬁ  cult to iden-
tify. Single-photon emission tomography ( SPET or SPECT ) with 
the dopamine D
2/3 ligand [123I]IBZM showed increased binding 
in the striatum.(18) There were signiﬁ  cant correlations between 
IBZM binding in the left and right striatum and measures of reac-tion time and verbal ﬂ  uency, but not of mood as such. This ﬁ  nding 
has been conﬁ  rmed with a PET ligand.
(19) Increased D2/3 binding

(19) Increased D2/3 binding 
in the striatum probably reﬂ  ects a reduced dopamine function, 
whether due to a reduced release or secondary upregulation of receptors. Binding to the 5-HT1a receptor appears to be reduced in unipolar depression, an effect also present in recovered atients.
(20)In recent years, new SPET and PET ligands for the serotonin and 
dopamine transporter have become available (see Chapter 2.3.6 by Grasby). For the serotonin transporter in acute depression, the story is not consistent.
(21,22) Binding to the dopamine transporter 
appears to correlate with depressive symptoms in healthy volun-teers.
(23) Hence trait effects may confound state effects and vice 
versa. Isotope-based imaging has been slow to develop a wide choice or availability of ligands, hence its role has been largely to follow rather than stimulate new ideas. Its speciﬁ  city does mean that it can 
critically test hypotheses about speciﬁ  c receptors.

Such ligands have not yet made an impact on treatment st rategies, 
as dopamine receptor ligands have for the antipsychotics. However, there are interesting preliminary conclusions: for example, drugs that bind to the serotonin transporter appear to saturate the site at therapeutic doses and increase the availability of dopamine reuptake sites.
(24)
In summary, functional imaging has served to implicate
frontal and limbic rather than posterior brain areas, in broad conﬁ  rmation of anatomical conclusions derived from observing 
the effects of lesions or brain stimulation. Relevant neuropsycho-
logical challenges are now being incorporated into imaging
protocols and we have the ﬁ  rst example of an imaging-led treat-
ment innovation—deep brain stimulation. Finally, ‘functional’ abnormalities may importantly predict structural abnormality in depression.
(b) Neuroendocrine challenge tests

Secretion of hormones in the anterior pituitary is under control, both direct and indirect, of central neuronal cell bodies that may project relatively widely within the brain. The secretion of a given hormone in response to speciﬁ  c precursors or agonists for indi-
vidual neurotransmitter receptors has been proposed as a way of testing the security of such connections. Hormone secretion provides a bioassay of the system of interest. There is a measure of consensus about the ﬁ  ndings in major depression, which, indeed, 
forms the most consistent basis for our understanding of disturbed neurotransmission in depression. However, the approach no longer leads the neurobiology, and merits consideration instead, in the more speciﬁ  c context of neuroendocrine function (see Chapter 2.3.3).

The main ﬁ  ndings are described below.
Neuroendocrine drug challenge suggests attenuated seroto-
nergic function and increased cholinergic function in depression. 
Reduced responses to adrenergic and dopaminergic challenge also suggest impaired neurotransmission. Interpretation of tests with agonists is always difﬁ  cult, because blunting may occur in an 
overactive system that has been downregulated. In addition, if the secretion of the assay hormone itself is actually directly affected by the state of depression, interpretation in terms of speciﬁ  c neu-
rotransmitter abnormalities may be misleading. This is a particular 
problem for ACTH/cortisol responses (see below). In fact, enthusi-
asm for neuroendocrine surrogate markers of monoamine trans-
mission within the brain has probably diminished in recent years, but the paradigm of drug challenge nevertheless remains interesting. 
We must assay brain responses of the monoamine projections more

We must assay brain responses of the monoamine projections more 
centrally involved in mood regulation.
(c) Hypercortisolaemia
About half of all patients with major depression have a raised 
cortisol output, which tends to return to normal on recovery. It is most consistently associated with an ‘endogenous’ pattern of

661
illness (see Chapter 4.5.3). While cortisol is always regarded as a 
‘stress’ hormone, and is secreted in response to various types of acute stress, the stresses that commonly result in long-termhypercortisolaemia are poorly understood. The idea that there is a relatively speciﬁ  c link between chronic high cortisol levels and 
mood disorder is notably persistent. In major depression thereis peripheral hypertrophy of the adrenal glands, measurable in MRI body scans, and an enhanced response to corticotrophin. The MRI change, like the hypercortisolaemia itself, reverses on recovery.
(25)
Suppression of cortisol secretion occurs normally via glucocorti-
coid receptor-mediated inhibitory feedback to the hypothalamus; it is readily produced by dexamethasone, which is a potent exoge-nous glucocorticoid (the dexamethasone suppression test ( DST )).

coid receptor-mediated inhibitory feedback to the hypothalamus; it is readily produced by dexamethasone, which is a potent exoge-nous glucocorticoid (the dexamethasone suppression test ( DST )). 
For example, Non-suppression of endogenous cortisol after dexa-methasone occurs in Cushing’s disease. It implies either reduced feedback and/or enhanced central drive to release cortisol. It was initially observed that the 1-mg DST showed high speciﬁ  city 
(96 per cent) and sensitivity (67 per cent) as a putative diagnostic test for melancholia.
(26) At this point of time the result attracted 
intense interest, but has since proved difﬁ  cult to generalize. The 
high speciﬁ  city established against normal controls was less against

high speciﬁ  city established against normal controls was less against 
other patient groups. Thus, DST non-suppression has not been accepted as a diagnostic test. This failed effort to give medical respectability to psychiatric diagnosis came to devalue what remains an important observation. Non-suppression usually reﬂ ects hypercortisolaemia, which is itself a robust phenomenon of 
mood disorder that requires explanation like any other core bio-logical symptom. Other symptoms that we identify as part of the depressive syndrome lend themselves less easily to investigation. The DST also has potential clinical uses beyond diagnosis. DST non-suppression predicts a low placebo response rate to drug treatment,
(27) and hypercortisolaemia predicts a low rate of clinical 
response to psychological intervention.(28)

It remains unclear whether cortisol contributes to the clinical 
state of depression by a direct action on the brain. Exogenous cortisol administration is associated with affective symptoms, and chronic excessive cortisol secretion commonly appears to produce depressive symptoms in Cushing’s disease. An HPA axis programmed to hypersecrete cortisol under stress could be a patho-genic mechanism explaining why depression or mania develops. This view has provoked efforts to treat mood disorder by inhibition of cortisol synthesis with metyrapone or blocking the post-synaptic receptors. The effects of such manipulations appear primarily, and unexpectedly, to influence cognitive function more than mood per se. Thus the anti-glucocorticoid, mifepristone improved spatial working memory in bipolar depression
(29) and the anti-

mineralocorticoid, spironolactone signiﬁ  cantly impaired selective 
attention and delayed recall of visuospatial memory in healthy volunteers without effects on CCK-induced panic anxiety.
(30)
There is a ﬁ  nal twist: when depressed patients are given large 
doses of cortisol they tend to show acute mood enhancement(31)
and oral dexamethasone has been reported to elevate mood in major depression, especially in hypersecretors.
(32) This leads to the 
converse hypothesis that an HPA axis appropriately adapted to chronic stress early in development might be unable to mount a normal effective response to acute stress later in life. Cortisol may then be seen as a euphoriant (or antidepressant), and hypercorti-solaemia as an antidepressant response of the stress-regulating mechanisms of the brain. Based on this view, all cortisol levels seen 
in depression may be set inappropriately low for the ongoing stress, however high or low they are compared with the normal range.

Whether one supposes cortisol levels to be set too high or too 
low in depression, it remains inconvenient that either a suppression or an augmentation of steroid effect seems, initially at least, to elevate mood. A way out of this complication may lie in cortisol’s action on two receptors in the brain (the glucocorticoid and min-
eralocorticoid receptors) that may have opposite actions. However, 
we still need better-controlled replicated data on the effects of steroid manipulations, both in at-risk subjects and in major depres-sion. It is also possible that peripheral cortisol levels are largely irrelevant to the brain and that receptor regulation may critically modulate their central action: one challenging hypothesis is that antidepressants work through changing receptor disposition.
(33)
An increased cortisol production is associated with an increased

(33)
An increased cortisol production is associated with an increased 
release of hypothalamic β-endorphin and probably a pulsatile 
increase in ACTH. The paraventricular nucleus of the hypothala-mus represents the highest level of dedicated neurones in the HPA axis. The neurosecretory cells of the paraventricular nucleus release the peptides CRH and A VP into the portal hypophyseal blood. These hormones in turn stimulate the release of ACTH from the anterior pituitary. Major depression is characterized by a blunted ACTH response to CRH, an elevated level of CRH in the cerebro-spinal ﬂ  uid, and increased numbers of neurones expressing CRH 
mRNA in the paraventricular nucleus of the hypothalamus post-mortem.
(34) CRH is not conﬁ  ned to the paraventricular nucleus,

(34) CRH is not conﬁ  ned to the paraventricular nucleus, 
but is expressed in a variety of other central nuclei whence it can produce anxiogenic behavioural effects. CRH receptors, which exist in two forms, are widely distributed in the hypothalamus and cortex. A related peptide, urocortin, has a similar pharmacology. Knocking out the CRH-1 receptor gene in mice impaired the HPA stress response and reduced anxiety-like behaviour. Non-peptide antagonists of CRH action, and of other peptide hormones impli-cated in stress responses have been taken very seriously as putative anxiolytics or antidepressants.
(35) If effective, they will be among 
the ﬁ  rst of a new generation of truly novel treatments based on 
peptide neurotransmission. The failure to see new compounds of this general kind by now is disappointing, and in the case of a neurokinin antagonist, aprepitant, there has been a high proﬁ  le

peptide neurotransmission. The failure to see new compounds of this general kind by now is disappointing, and in the case of a neurokinin antagonist, aprepitant, there has been a high proﬁ  le 
failure in major depression.
(36)
(d) Thyroid abnormalities
In unselected major depression, thyroid hormone levels are usually normal, but there may be abnormalities of the thyrotropin (thyroid-stimulating hormone) response to thyrotropin-releasing hormone. The thyrotropin response is blunted in a signiﬁ  cant number of 
patients, but this effect is poorly understood and has few accepted clinical associations. In contrast, a subgroup of patients may show an enhanced thyrotropin response with normal thyroid hormone levels (referred to as grade II hypothyroidism). These associations and the use of thyroid hormones in treatment suggest that there is more to be learned in this area (see Chapter 4.5.8).
(e) Sleep disturbance

Sleep is often disturbed in depression but in a variety of ways. Early-morning waking is the most typical in endogenous or melan-cholic depression, with the sleep patterns in such patients being similar to those seen in patients with mania. Trouble getting to sleep, frequent awakenings, and unsatisfactorily prolonged sleep 4.5.6 neurobiological aetiology of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 662
are also commonly seen in depression. Like other biological mani-
festations of the disorder, the extent to which sleep is simply a con-sequence of the state of depression or a contribution to its biology is uncertain. Patients with severe depression or mania may respond to sleep deprivation with a transient elevation in mood. It implies that the sleep–wake cycle is directly involved with mood regulation and its disorder.
In severe depression (melancholia) the typical effects are a reduc-
tion in the total length of slow-wave sleep and a shortened latency in the appearance of rapid eye movement ( REM ) or dreaming 
sleep.
(37) The cholinergic projections from the hindbrain may

sleep.
(37) The cholinergic projections from the hindbrain may 
be REM-ON cells, while serotonergic and noradrenergic cells may be REM-OFF cells. The disturbed sleep of depression could be due to an increased cholinergic and/or a decreased serotonergic/noradrenergic drive; simplistic though it sounds, the experimental evidence is supportive. Depressed patients challenged with a cho-linergic agonist in the second non-REM period enter REM signiﬁ  -
cantly faster than psychiatric and normal control subjects. The reduced sensitivity of the noradrenergic system is suggested because clonidine fails to suppress REM in depressed patients compared with controls.
(38) Tryptophan depletion (to attenuate 5-HT function) 
partially mimics the changes seen in depression in recovered patients.
(39)
Sleep tends to recover on recovery from depression, and the

(39)
Sleep tends to recover on recovery from depression, and the 
tricyclic antidepressants in particular suppress REM sleep. However, sleep disturbance may be an early predictor of relapse, and disturbed sleep parameters predict a poor response to cognitive behaviour therapy.
(40) Indeed, depressed patients may have inher-
ently weak slow-wave sleep processes because unaffected subjects with a family history of depression show reduced slow-wave sleep and increased REM density in the ﬁ  rst sleep cycle
(41).
Interest in sleep as a fundamental key to understanding mood 
disorder has waned in the last two decades. However, its neurobiol-ogy is increasingly well understood, and its time may come again.
(f) Monoamine metabolite turnover

The earliest studies to investigate the actions of tricyclic antidepres-sants highlighted their actions on the turnover of the monoamine metabolites in animal brain. The ‘monoamine theory of depression’ proposed the reduced functioning of monoamine transmission in depression. Therefore it was natural to seek relevant measures of monoamine chemistry in the cerebrospinal ﬂ  uid of patients and 
controls. The study of what became irreverently known as ‘neural urine’ and indeed of urine itself, since peripheral measures of monoamine turnover are also potentially relevant, virtually deﬁ  ned 
a decade of biological psychiatry in the 1970s and 1980s. Drugs had similar effects on neurotransmitter turnover as seen in animal studies, demonstrating that the human techniques were sufﬁ  ciently

a decade of biological psychiatry in the 1970s and 1980s. Drugs had similar effects on neurotransmitter turnover as seen in animal studies, demonstrating that the human techniques were sufﬁ  ciently 
sensitive. Indeed the monoamine theory is, at its best, a theory 
about drug action because the monoamine and metabolite changes produced by illness in patients have proved remarkably 
unconvincing.
(42) The ﬁ  ndings for the noradrenaline metabolite 
MHPG and the 5-HT metabolite 5-hydroxyindoleacetic acid were negative. The dopamine metabolite homovanillic acid did show 
the predicted decrease, but only signiﬁ  cantly in women. There were 
trends to modest increases in all the major metabolites in mania. Although disappointing, cerebrospinal ﬂ  uid studies could never 
reﬂ ect the activities of smaller groups of neurones localized in areas 
critical for the modulation of mood. Such a focus is only possible in isotope imaging (PET or SPET) or better post-mortem studies 
of the brain.

(g) Tryptophan depletion

The most convincing evidence that 5-HT is intimately involved in mood disorder has come from depletion of tryptophan, the amino acid precursor of 5-HT. The level of tryptophan in both peripheral blood and the brain can be driven to very low levels by a short-term low-protein diet and subsequent loading with large neutral amino acids. These compete with tryptophan for access to the brain amino acid transporter and also increase its peripheral metabolism, which results in the reduced synthesis and release of 5-HT. Initial obser-vations appeared to bear primarily on the mechanism of drug action. Thus, patients who had recovered from major depression while taking a serotonin-selective reuptake inhibitor experienced a clear-cut return of severe symptoms lasting for several hours after tryptophan depletion. This ﬁ  nding has now been critically 
extended to patients with a history of recurrent major depression

extended to patients with a history of recurrent major depression 
who were euthymic but not taking any medication.
(43) Prominent 
objective symptoms of retardation and cognitive distortion returned in a stereotyped and severe way, reﬂ  ecting previous 
symptoms. The effects on mood in patients who have had aprevious episode of depression are qualitatively different from the more minor changes seen in normal female controls oreven subjects with a strong family history. This may imply the 
formation of a form of neurobiological template, which increases the vulnerability to subsequent relapse or recurrence. The imme-diacy of the link between neurotransmitter function and
symptoms may be the reason why patients with recurrent major depression need long-term treatment with antidepressant drugs to remain well.
(h) Does mood disorder have a functional neuropathology?
Severe mood disorder is virtually deﬁ  ned by its frequent recur-

rence or its chronicity. The ﬁ  rst episodes of severe depression occur 
more frequently with increasing age and tend to be more refractory to treatment. Severe mood disorder is associated with ventricular enlargement and sulcal prominence.
(44) Late-onset depression is 
characterized by pronounced impairments in most areas of cogni-tive function, in particular executive function and processing speed and is increasingly regarded as having a quasi-neurological quality. Indeed, there is an increased rate of white matter lesions, perhaps related to vascular disease, in older patients.
(44) The relationship 
between cognitive deﬁ  cits and underlying neuropathological chang-

es requires further examination. Elderly patients with early-onset depression demonstrate greater preservation of executive func-tioning and processing speed, which may reﬂ  ect partially distinct 
disease processes possibly mediated by different neuropathological mechanisms.
(45) The key hypothesis must be that it is the particular 
pattern of functional disruption resulting from any cellular pathol-ogy that increases the risk of depression. It may be reasonable to describe such a change as a functional neuropathology.
In younger patients, the issue is whether depression per se leads 
to a functional neuropathology. In patients with unusual refracto-riness and chronicity, MRI scanning again suggested reduced grey matter parameters, most signiﬁ  cantly in the left hippocampus but

to a functional neuropathology. In patients with unusual refracto-riness and chronicity, MRI scanning again suggested reduced grey matter parameters, most signiﬁ  cantly in the left hippocampus but 
also more diffusely in the left parietal and frontal association cortices. Left hippocampal grey matter density was correlated with measures of verbal memory, supporting the functional signiﬁ  cance

663
of the imaging changes. In contrast, patients with severe illnesses 
fully responsive to treatment showed no differences from controls. Any ﬁ  nding in the chronic group could predate the onset of depres-
sion, or be the result of the illness process or its treatment. It is fashionable to attribute structural changes in depression to hyper-cortisolaemia, but in this study that was not the explanation.
(46)
A failure of BDNF, related neurogenesis or loss of synaptic plasticity is also a possibility. Reduced hippocampal volume is a relatively consistent ﬁ  nding in many studies of modest size which have 
also implicated inter-linked structures in basal ganglia and thalamus.
(47)
Rather surprisingly, a correlation between lifetime duration of 
illness and memory performance was also seen in a very large outpatient sample studied after recovery from a discrete episode.
(48)

(48)
It favours a toxic link between the burden of depression and cogni-tion, which has implications for public health. It also means that the mechanisms associated with very severe depression are also relevant in less severe ambulant forms.
Post-mortem studies of the brain in mood disorder have been rare 
and are limited by tissue availability. Such studies in elderly depres-sion have greater potential validity than the much more num erous investigations of schizophrenia. The Stanley Neuropathology con-sortium has made samples of tissue widely available from small but well-characterized patient series. In the hippocampus, the most consistent ﬁ  ndings are of reduced GABA function and abnormal 
measures of synaptic density or neuronal plasticity.
(49) Such studies

(49) Such studies 
have seldom focused on other ‘candidate regions’ such as the inferior frontal or cingulate cortex or amygdale.
(50) Several studies suggest a 
particular involvement of glial cells.(51) Since glia support the energy 
requirements of neurones, and their deﬁ  cient function could account 
for aspects of the imaging abnormalities found in these disorders: elevated levels of glucocorticoids acting on glia could change their function, or glial changes could represent responses to primary neuronal withdrawal (see also Chapter 2.3.5).
Post-mortem studies can also address the neurochemistry,

Post-mortem studies can also address the neurochemistry, 
perhaps more directly and completely than other methods. Normal ageing is accompanied by a decline in a variety of indices of mono-amine function including presynaptic markers of 5-HT innerva-tion. In a small series of depressed suicides, there were 54 per cent fewer neurones in the dorsal raphe nucleus expressing SERT mRNA compared with controls.
(52) Whether a reduced serotonergic 
innervation is the critical change that increases the vulnerability to mood disorder of patients with advancing years is not yet estab lished. 
If so, the potential for MDMA to have long-term effects in heavy users is real and worrying.
(53)
In suicide, post-mortem ﬁ  ndings have broadly paralleled those

(53)
In suicide, post-mortem ﬁ  ndings have broadly paralleled those 
in depression, with an important emphasis on 5-HT metabolism and neurotransmission (see Chapter 4.15.3). Whether 5-HT neuro-transmission, perhaps like that involving the other monoamines, represents a functional domain implicated independently in a variety of psychiatric syndromes and behaviours remains to be well established.
Mood disorder has an important neurobiological basis. This stretch-es from a vulnerability, which seems to be attributable to polymor-phism in genes critical to stress regulation, through the impact that early experience has on the subsequent programming of the brain for stress responses, to the ﬁ  nal responsiveness when encountering

particular personal adversity in later life. Biological studies have highlighted the role of key brain areas within the limbic system such as the cingulate cortex and amygdala. We are still a long way from understanding, with any precision, the critical connections andcellular mechanisms, but the function of monoamine neuronesgenerally, and of serotonergic projections in particular, is closely associated with mood regulation. Peptide neurotransmitters have long seemed likely to play a central role in stress regulation, buttheir potential as targets for antidepressant drug action are yet to befulﬁ lled. Finally, observations in the most chronic illnesses and in 
the elderly with depression have highlighted the possibility of a functional neuropathology underlying severe mood disorder. Depression seems to be critically related to the evolving story around neurogenesis in the brain. It is perhaps appropriate that its 
resolution will require fundamental advances in brain science: psy-

chiatry has always posed, or anyway implied, the most demanding of scientiﬁ  c questions: how does the brain work?
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4.5.7 Course and prognosis 
The importance of course
Ever since Kahlbaum’s monograph 1863(1) the course and outcome 
of mental disorders have played important roles as criteria and validators of psychiatric classiﬁ  cation. The prognosis is fundamen-

tal for doctor and patient when deciding whether to start long-term prophylactic medication and, at a later stage, whether to stop a successful long-term treatment. Course is a crucial factor in esti-mating the social consequences, costs, suicide risk, and mortality associated with mood disorders.
The description of course includes the age of onset, episode 
length, recurrence of episodes, residual symptoms between episodes and outcome (remission, chronicity, death). These aspects are covered in this chapter.
Stability of the diagnoses of mood disorders
Mood disorders can be roughly sub-classiﬁ  ed into unipolar mania, 
bipolar disorder, and unipolar depression.(2) The three groups differ 
signiﬁ  cantly as regards family history, personality, course and out-

come, including mortality. Unipolar mania has not yet been studied extensively, and for this reason will not be dealt with here.
Distinguishing between bipolar disorder and unipolar depressive 
disorder is hampered by the fact that the diagnosis of unipolar depression is always uncertain. Many depressives are hidden bipo-lar patients: a long-term follow-up study over 27 years showed a constant rate of diagnostic change from depression to hypomania of 1.25 per cent per year of follow-up. As a consequence of this diagnostic instability, the exact ratio of bipolar to unipolar depres-sive subjects in the population is unknown; modern estimates range from 1:5 to 1:1. The discussion of bipolar disorder has there-fore to take account of its unipolar counterpart.
Onset

Onset
In patients admitted to hospital between 1913 and 1940 and not treated by electroconvulsive therapy or modern psychotropicdrugs, bipolar disorder clearly manifested earlier than unipolar depression; this ﬁ  nding is conﬁ  rmed by modern community stud-
ies. In most patients bipolar disorder begins during adolescence but in some cases may already manifest in childhood. Unfortunately pediatric psychiatry cannot yet provide prospective data from large representative community studies on the onset and course ofbipolar disorder starting in childhood or adolescence.
In the offspring of bipolar parents social functioning up to the 
age of 18 develops normally before the onset of their illness.
Bipolar disorders usually begin as depression, and it takes a further 
5 years on average until the ﬁ  rst manic syndrome manifests.
(3)
There may be unspeciﬁ  c prodromal symptoms in the form of

(3)
There may be unspeciﬁ  c prodromal symptoms in the form of 
mood lability, vegetative lability, somatization, or being hyper-alert or easily excited; there may also be discrete cognitive impairment present before the onset of the affective disorder.
(4) After the onset 
of the disorder social functioning often begins to be impaired.
The ﬁ  rst depressive and manic manifestations are commonly 
mild, brief, or uncharacteristic, and are often only diagnosed in retrospect after years.
Prospective epidemiological studies in adolescents and young 
adults found the onset of bipolar disorder to occur in the teens (with means and medians around 15 years or later), whereas studies of hospitalized patients date its onset in retrospect in the early 20s or in the 30s.
Bipolar-I illness manifests earlier than bipolar-II and psychotic

Bipolar-I illness manifests earlier than bipolar-II and psychotic 
bipolar disorder. Late-onset bipolar disorder is extremely rare but does occur and may be associated with speciﬁ  c neuropathology. 
An early age of onset of the disorder, usually manifesting as depres-sion, is correlated with suicidality, comorbid substance-use disor-
der and a rapid cycling course.
A two-peak distribution of the age of onset has sometimes been 
described for both bipolar disorder and depression in men and 
women, with no speciﬁ  c association in women between the second 
peak and the menopause.
Duration of episodes

Most episodes are short, but 10 to 20 per cent become chronic (lasting more than 2 years); the distribution of episode length is log normal, and therefore percentiles and not averages should be used as parameters. Using data collected a century ago on the natural length of episodes of mania and bipolar disorder, mainly among hospitalized patients, it is possible to compute a median length of 4 to 6 months for mania and 5 to 6 months for bipolar disorder. These ﬁ  gures do not differ from those obtained today despite a 
wide range of antimanic and antidepressant treatments. Among hospitalized bipolar patients episode length (median) was 4.2 mo nths; 
25 per cent of bipolar episodes lasted more than 7.3 months.
About 20 to 30 per cent of episodes are biphasic (mania with sub-

sequent switch into depression, or depression with subsequent, switch into hypomania/mania); such high switch rates were already observed before the introduction of electroconvulsive therapy and 
antidepressants. An effective treatment does not induce a switch 
but increases (compared to placebos) the rates of responders; and the response is a precondition for the natural switch.
Recurrence of episodes
Recurrence is typical of mood disorders. It can be described by the number of episodes, the length of intervals (measured from remission to the onset of a new episode), and the length of cycles 4.5.7 course and prognosis of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 666
(measured from the beginning of one episode to the beginning of 
the next). In prospective studies, time to the onset of a new episode is frequently used as a parameter for survival analyses and frailty analyses of recurrence.
In both bipolar disorder and unipolar depression the time 
from the ﬁ  rst to the second episode is on average much longer than 
from the second to the third episode and so on. This progressive shortening of cycles and free intervals then levels off and ﬂ  uctuates 
around a certain (but still variable) individual limit. Most pub-lished data on interval length or cycle length are methodologically ﬂ awed because they have not been corrected for the number of

around a certain (but still variable) individual limit. Most pub-lished data on interval length or cycle length are methodologically ﬂ awed because they have not been corrected for the number of 
episodes/cycles observed. Nonetheless, multiple episodes obviously follow each other in more rapid succession than a few episodes distributed over a lifetime. Statistically, a normal distribution of cycle length can be obtained by log n transformation. Even 
after taking episode numbers into account, there is a clear intra-individual trend to a progressive shortening of cycle length, as demonstrated by frailty analyses
(5) dimming the prognosis for both 
bipolar disorder and unipolar depression. Initial cycle length tends to be shorter in late-onset than in early-onset mood disorders, increasing the risk of recurrence in the elderly.
Precipitating events play an important role in the onset of the 
ﬁ rst few affective episodes; thereafter recurrence seems to become

ﬁ rst few affective episodes; thereafter recurrence seems to become 
gradually autonomous with stressful events contributing little or nothing to the process. Stressors may not only precipitate episodes but also increase a pre-existent vulnerability, sensitizing the individual and thereby making him or her more vulnerable to further episodes (kindling effect). In bipolar illness there is no difference in the quality or quantity of stressors precipitating depressive and manic episodes; a legacy or the loss of a relative can induce depression or mania. The sensitivity to stressors has also a 
genetic component.
Over a patient’s lifetime his condition continuously ﬂ  uctuates 
on a dimension of severity, which ranges from psychotic, via major and minor syndromes (cyclothymic and minor bipolar disorders), 
cyclothymic temperament within the norm, symptomatic to 
symptom-free.

The NIMH Collaborative Depression Study with annual assess-
ments of outpatients over an average of 13 years, demonstrated that bipolar-II patients spent slightly more time with symptoms/syndromes (33 per cent) than bipolar-I patients (27 per cent). In both subtypes of bipolar disorders depressive periods were three 
times more common than manic periods
(6) but bipolar-I patients 
suffered more from psychotic features. In a 25-year follow-up study of hospitalized mood disorder patients, manic and depressive episodes were about equally present in bipolar-I patients, whereas in bipolar-II patients the course was dominated by depression.
Daily assessments of the course by the life-chart methodology 
over more than 3 years conﬁ  rmed that bipolar outpatients spent a 
three-fold greater amount of time in depression than hypomania. But it was also shown that bipolar-I patients spent signiﬁ  cantly

three-fold greater amount of time in depression than hypomania. But it was also shown that bipolar-I patients spent signiﬁ  cantly 
more time in hypomania than their bipolar-II counterparts but an 
equal time in depression; in more than half the time the patients were euthymic.
Over lifetime bipolar patients experience twice as many episodes 
as unipolar depressives, a difference which is not explained by 
the manifestation of manic episodes in addition to depression. 
The total number of episodes observed depends on the length of 
observation. In a 22- to 26-year follow-up study, bipolar patients experienced a median of 10 episodes, but depressive patients only 
four. A family history of mood disorders increases recurrence. The proportion of mania to depression remains fairly stable across multiple episodes, but over their lifetime patients spend more time in depression than in mania.
Outcome

Outcome
(a) Incomplete remission of episodes
Remission after bipolar episodes is frequently incomplete in terms of symptomatic and functional recovery. Residual symptoms are common in patients in both psychiatric and general practice settings and bipolar subjects identiﬁ  ed in community studies. 
Residual depressive symptoms are more impairing than hypomanic symptoms, which may even enhance functioning.
(7) The chronic 
residual symptoms are mainly depressed mood, anxiety, and somatic disturbances, such as insomnia, hypersomnia, headaches, neurasthenic complaints, reduced libido, and gastrointestinal symptoms. Functional recovery was found to develop later than symptomatic recovery. Short-term outcome is less favourable in patients with agitation, rapid cycling, poor premorbid functioning, comorbidity with anxiety disorders, social phobia, substance use, OCD, obesity, personality disorders, sexual trauma, abuse, and behaviour disorders in childhood.
(8) Manic versus mixed episodes

(8) Manic versus mixed episodes 
do not differ in outcome after 1 year.
(b) Long-term course and outcome
The long-term course and outcome of bipolar disorders is charac-terized by high recurrence rates, frequent residual symptoms between episodes; compared to depression they carry a higher risk of suicide attempts but lower risk of suicides.
Bipolar disorder has a poorer outcome than depression and there 
is no burn-out with age. After a follow-up of 22 to 26 years, deﬁ  ni-
tive recovery (at least 5 years with good social adaptation) was found in 25 per cent of 186 depressive subjects, whereas the ﬁ  gure 
was only 16 per cent of the 220 bipolar patients; a chronic course lasting at least 2 years without remission was present in 12 to 14 per cent of depressive and bipolar patients. A chronic course is associated with early life adversity, including sexual and physical abuse.
Comorbidity with alcoholism, a factor known to correlate

Comorbidity with alcoholism, a factor known to correlate 
with poorer outcome and increased mortality, was found in 
30 per cent of the bipolar patients. Modern treatment has improved the outcome of mood disorders by reducing chronicity and rehospitalization.
Recurrence (number of hospital admissions) may increase the 
risk of dementia.
Mortality
Mortality is expressed by the standardized mortality ratio ( SMR ) in 
comparison with the normal population (SMR = 1.0). Data on hospitalized psychiatric patients in Sweden
(9) give an overall SMR 
for bipolar men of 2.5 and for women 2.7. The high mortality is a consequence not only of suicides (SMR = 15.0 for males and 22.4 for females) but of most other causes of death (excluding cancer): infections, endocrine, cardiovascular, cerebrovascular, respiratory and gastrointestinal disorders, homicides, accidents, trafﬁ  c acci-
dents and secondary substance-use disorders (mainly alcohol use disorder), etc. This is true for both men and women.

667
Consequences for treatment
Incomplete recovery and high recurrence are the main problems 
in the treatment of bipolar disorders. In the treatment of an acute episode the primary goals are full recovery and the prevention of relapses. The length of treatment of an acute episode depends on its estimated spontaneous duration, which may be derived from earlier episodes. In case of doubt, 6-months’ maintenance treat-ment after recovery is the rule. Long-term prophylaxis should be maintained lifelong.
Most time is spent in depression, therefore a combination
of a mood stabilizer with an antidepressant is often indicated.The same is true for the long-term medication of the disorder, where combined treatments are the rule.
Special attention should be given to suicidal bipolar patients, 
who should preferably be treated with drugs shown to be antisui-cidal (lithium or clozapine combined often with antidepressants). A lifelong study demonstrated a three- to ﬁ  ve-fold reduction of

who should preferably be treated with drugs shown to be antisui-cidal (lithium or clozapine combined often with antidepressants). A lifelong study demonstrated a three- to ﬁ  ve-fold reduction of 
suicides. Comorbidity with alcohol use disorder increased the mortality but not the suicide rate.
Major depressive disorder (MDD)
Onset
Unlike bipolar disorder, depression may start at any time of life and has therefore a later mean age of onset. In the United Kingdom a mean age of onset of 33 years was found in hospitalized patients. In a large United States study of outpatients the mean was 29.4 years, but in 53 per cent of cases the onset was before the age of 21. The distribution of the age of onset is bimodal, with peaks in the 30s and 50s.
Prospective data suggest that MDD very often begins as sub-

threshold depression; this is especially true for late-onset cases, where the full MDD episodes also tend to last longer and to become chronic more often. Age of onset and earlier episodes assessed in retrospect are subject to dramatically false recall.
There is no true dichotomy between early-onset and late-onset 
depression but a continuous distribution accompanied by a systematic decrease in genetic vulnerability (morbid risk among ﬁ rst-degree relatives) and an increase in precipitation by environ-
mental factors. The correlation of age of onset with the genetic component was found in both patient and community samples. Childhood traumata create a vulnerability which promotes earlier onset and higher comorbidity.

The length of depressive episodes is log normally distributed; there-fore simple mean values are meaningless. Compared to bipolar disorder, episodes of depressive disorders last about 1 month lon-ger (median duration of 5.4 months); and about 18 to 25 per cent of patients develop chronic depression with a minimum duration of 2 years. In the general population, among whom there are many untreated cases of depression, episodes were found to be shorter; the 25th, 50th, and 75th percentiles were 4, 8, and 16 weeks respec-tively for recurrent episodes.
Chronicity is clearly correlated with age and persistent cognitive 
deﬁ cits; it is common in the elderly but  relatively ra re in ad olesc ents. 
As is in bipolar disorder chronicity is associated with early life adversity, including sexual and physical abuse.Recurrence of episodes

Major depression is recurrent in about 85 per cent of cases; compared to bipolar disorders, however, depressive patients experience only half as many episodes over their lifetime. The cycle length (time from the start of an episode to the start of a subsequent episode) is consequently longer than in bipolar disorders. There is also a systematic shortening of cycle length with the increasing number of episodes, as shown by frailty analyses. The precipitation of episodes by life events—frequent initially—decreases as the number of episodes grows; the periodicity becomes increasingly autonomous. A twin study suggests that undesirable life events play a signiﬁ  cant role in the recurrence of depression in women with a 
low genetic risk.
In a recent large representative record study in Denmark ( N =

In a recent large representative record study in Denmark ( N = 
20 350 ﬁ  rst admissions) unipolar depressives had strikingly lower 
recurrence rates (hospitalizations) than bipolars, the rates for both correlating with the number of previous episodes.
(10) The authors 
concluded: ‘The course of severe unipolar and bipolar disorder seems to be progressive in nature despite the effect of treatment and irrespective of gender, age and type of disorder’ . Risk factors for recurrence are previous recurrence, long duration of episodes, late onset, age, severity, and incomplete remission.
Residual symptoms represent a strong risk factor for further 
recurrence; a survival analysis by Paykel et al.
(11) found a three-fold

(11) found a three-fold 
higher risk of recurrence (76 per cent) in patients with residual symptoms than in those without (25 per cent). This sub-threshold depressive morbidity is clinically relevant and a clear risk factor for future recurrence and suicidality, especially in the elderly.
Outcome
In long-term follow-up studies, 43 to 52 per cent of depressed outpatients became symptom-free between their episodes, and the other half continued to suffer from dynamically ﬂ  uctuating residual

In long-term follow-up studies, 43 to 52 per cent of depressed outpatients became symptom-free between their episodes, and the other half continued to suffer from dynamically ﬂ  uctuating residual 
syndromes or symptoms. The corresponding cross-sectional status may be diagnosed as dysthymia, recurrent brief depression, minor depression, residual syndromes and symptoms, or as full recovery. Initial severity and comorbidity are positively correlated with poor outcome in terms of poorer functioning and incomplete remission. In a British study residual symptoms of major depression, deﬁ ned by a score of eight or more on the 17-item Hamilton 
Depression scale, were found in 32 per cent of 60 patients 12 to 15 months after remission.
(11) In a large cross-cultural study 
(N = 968) conducted over 9 months, between 25 and 48 per cent of 
cases experienced complete remission,(12) rates which also depended

cases experienced complete remission,(12) rates which also depended 
on the severity of the depression and comorbidity. Severe residual symptoms correlate with long-term morbidity, impaired social func-tioning at work and in relationships and suicidal behaviour, espe-cially in the elderly, amongst whom re mission is present in only 
about one third of cases.
Recent evidence from a 30-month prospective community-based 
cohort study of 75-year-old subjects suggests that a history of depression may increase the risk of senile dementia,
(13) which is 
compatible with ﬁ  ndings from Denmark that recurrence (number 
of hospital admissions) increases the risk of dementia.(14)
Mortality
Unipolar depressives have twice the mortality risk of the general population. The SMR (standardized mortality ratio) for suicide is 4.5.7 course and prognosis of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 668
21 for males and 27 for females;(9) these ﬁ  gures are higher than 
those for bipolar disorder. Many other causes of death are also more common among unipolar depressives than in the general population but to a lesser extent than among bipolar patients.
The frequently quoted suicide rate of 12 to 19 per cent is only 
valid for selected hospitalized patient samples, which, by deﬁ  nition, 
include many suicidal patients. In community and outpatient samp les, 
suicides account for a considerably smaller percentage of deaths; but long-term data is not available yet.
A lifelong follow-up study showed a suicide-preventive effect 
of administering low-dose antidepressant medication to severe unipolar depressives.
Course of other subtypes of mood disorders
Dysthymia
Subjects with a depressive personality disorder are especially prone to develop dysthymia. Dysthymia is by deﬁ  nition a chronic

Dysthymia
Subjects with a depressive personality disorder are especially prone to develop dysthymia. Dysthymia is by deﬁ  nition a chronic 
form of depression; nevertheless dysthymic patients have a similar outcome to major depressives: in outpatients the5-year recovery rate was 53 per cent. Dysthymia is highlycomorbid with other psychiatric disorders, especially with major depression (which it may precede or follow), so worsening the prognosis.
In the general population the recurrence rates of minor depres-sion are comparable to those of major depression, a fact con-ﬁ rmed by survival analyses.
(15) A diagnostic change from minor 
to major depression, or the reverse, is frequent during the course of mood disorders. Minor depression increases about ﬁ  ve-fold 
the risk for the development of major depression. Primary minor depression, like depressive symptoms in general, is a signiﬁ  cant

the risk for the development of major depression. Primary minor depression, like depressive symptoms in general, is a signiﬁ  cant 
risk factor for major depression. It can also represent a residual state of major depression and is a strong risk factor for further recurrence.
Among the elderly minor depression is common as a residual 
state. Both minor and major depression should be considered seriously as a target for preventive intervention and treatment; full recovery should be the goal.
(15)
Seasonal affective disorder
Many patients experience depressive episodes mainly in autumn and winter; mania tends to occur more often in summer. Seasonal affective disorder (SAD) remained seasonal in 70 per cent of 43 cases followed up over 2 to 5 years and in 42 per cent over 8.8 years.
(16) The diagnostic stability of SAD was fairly good (26 to

(16) The diagnostic stability of SAD was fairly good (26 to 
57 per cent). A large number of patients developed seasonal sub-threshold (subsyndromal) depression, whereas full remission was present in only 15 to 20 per cent.
Rapid cycling mood disorder
There is no generally accepted deﬁ  nition of rapid cycling; it is 
usually deﬁ  ned by the occurrence of at least four episodes per year, 
counting arbitrarily a biphasic episode as two episodes. Rapid cycling occurs almost exclusively in bipolar disorder; it is more fre-quent in females and in the bipolar-II subtype. Rapid cycling often manifests at an early age and increases the risk of suicide attempts but does not appear to represent a ﬁ  nal course pattern of bipolar

disorder: it is often a transient, non-familial manifestation of the disorder. In a prospective follow-up conducted over approximately 3 years the diagnosis was stable in about half the cases and the other half became simply recurrent (non-rapid cycling); in a control group 10 per cent of the non-rapid-cycling patients convertedto rapid cycling.
(17) Studies on the long-term prognosis are
inconclusive.

Antidepressant treatment can shorten the time to recovery. Therapeutic decisions on the length of acute treatment will depend on the length of the individual’s previous episodes and on the average episode length observed in follow-up studies. The length of affective episodes has probably not changed in 100 years. Antidepressants cannot shorten the episodes but can minimizethe symptoms. Treatment should be maintained for the full dura-tion of episodes, which are frequently masked, otherwise relapses must be expected. Full symptomatic and functional remission to the premorbid level should be the goal of treatment.
As with acute treatment, the choice of a long-term prophylactic 
medication should take into consideration the previous individual course of the disorder plus the general scientiﬁ  c knowledge of 
course and prognosis, and keep in mind the increased mortality,

course and prognosis, and keep in mind the increased mortality, 
especially the high suicide risk associated with depression. 
Recurrence is also a feature of mild cases, but in contrast to severe cases the suicide mortality is probably low.
Over a patient’s lifetime, each new recurrence is associated with 
a new risk of suicide and requires long-term prophylaxis with lithium, combined with low-dose antidepressants. This is especially necessary in the presence of suicidality in the previous or in the family history. If further studies conﬁ  rm that the recurrence of 
affective episodes increases the risk of dementia, such a long-term prophylaxis may become even more important.

Bipolar disorder and depression are serious illnesses responsible for most suicides in the population and are recurrent lifelong in most cases. The remission between episodes is often incomplete, increasing the risk of recurrence. Compared to depressionbipolar disorder is twice as recurrent and complicated by higher comorbidity with multiple somatic and psychiatric disorders, especially with substance-use disorder which shortens lifeexpectancy even more. Most patients spend about half theirlifetime in good health but the other half in largely depressive mood states fluctuating on the broad severity spectrum.Sub-diagnostic morbidity has been recognized as clinically very relevant and in need of permanent treatment. Great progress in the study of continuous ﬂ  uctuations has been made by the intro-
duction of the life-chart methodology and by computer-assisted

duction of the life-chart methodology and by computer-assisted 
daily assessments, methods which hold further promise.
(18)
Treatment should focus on all manifestations of the illness, 
including minor morbidity, in order to achieve full recovery to the premorbid level of functioning; in a long-term perspective the primary goal remains the prevention of recurrence, second-ary substance-use disorders and suicides.

669
Future studies should also try to reduce the dementia associated 
with affective disorders.(13,19,20)
I wish to thank Per Bech for his valuable comments and suggestions during the revision of this chapter.
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Maj, M., Akiskal, H.S., Lopez-Ibor, J.J., et al. (eds.) (2002). Bipolar disorder .
Marneros, A. (ed.) (2004). Das Neue Handbuch der Bipolaren und 
Depressiven Erkrankungen . Georg Thieme, Stuttgart.
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die Eintheilung der Seelenstörungen . A.W. Kafemann, Danzig.
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2. Angst, J. (2007). The bipolar spectrum. The British Journal of 
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symptomatic status of bipolar I vs. bipolar II disorders. International 
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disability in the course of bipolar I and II disorders. A prospective, comparative, longitudinal study. Archives of General Psychiatry ,
62, 1322–30.
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depression. Psychopathology ,31, 5–14.
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bipolar and unipolar disorder in Sweden. Archives of General Psychiatry ,
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in affective disorder. I. Case register study. The British Journal of 
Psychiatry ,172, 23–8.
11. Paykel, E.S., Ramana, R., Cooper, Z., et al. (1995). Residual symptoms 
after partial remission: an important outcome in depression. Psychological Medicine ,25, 1171–80.

12. De Almeida Fleck, M.P ., Simon, G., Herrman, H., et al. (2005). Major 
depression and its correlates in primary care settings in six countries. 9-month follow-up study. The British Journal of Psychiatry ,
186, 41–7.
13. Fischer, P ., Zehetmeyer, S., Jungwirth, S., et al. (in press). Risk factors 
for Alzheimer dementia in a community-based birth-cohort at age 75. Dementia and Geriatic Cognitive Disorders.
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4.5.8 Treatment of mood disorders
Evidence
Medication and physical treatments
(a) Acute treatments for depression
(i) Antidepressants: general issues
The ﬁ  rst modern antidepressants became available in the late 1950s,

Evidence
The ﬁ  rst modern antidepressants became available in the late 1950s, 
coinciding with introduction of randomized controlled trials in psychiatry. Tightening of licensing requirements has ensured good efﬁ cacy for new antidepressants. Overall efﬁ  cacy and speed of 
response of most antidepressants are similar. In addition to meta-analyses of speciﬁ  c antidepressant classes, there have been meta-
analyses conﬁ  rming efﬁ  cacy in speciﬁ  c patient groups or disorder 
subtypes, including dysthymia
(1) and the elderly.(2)
There are moderate, but not very large, effect sizes. About 30 per 
cent more subjects respond well on antidepressants than on placebo, partly because good response is often seen in placebo groups, prob-ably not due to the placebo but to spontaneous improvement and non-speciﬁ  c treatment effects such as those of seeing a helping

ﬁ gure, supportive psychotherapy, and hospitalization. Non-speciﬁ  c 
outcome tends to be worse among severely ill patients, but here also antidepressants may be less effective. Placebo-controlled trials are still mandated by regulatory authorities for new antidepres-sants, since comparisons between active drugs have high risk of type 2 error.
Table 4.5.8.1 lists the principal antidepressants and recommend-
ed doses, omitting minority drugs limited to a small number of countries. Some of the antidepressants listed are not available in all 
countries. Recommended doses depend partly on national authori-ties and readers should check the situation in their own country.
(ii) Reuptake inhibitors
Tricyclic antidepressants.  In addition to the tricyclics listed in 
Table 4.5.8.1, maprotiline and amoxapine are available in some countries. There have been many older efﬁ  cacy reviews, with 4.5.8 treatment of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 670
further studies accumulating as tricyclics have been included in 
placebo-controlled trials of new antidepressants.
Earlier views that tricyclics were more effective in endogenous 
and psychotic depressives have not been conﬁ  rmed and effects 
extend across a broad spectrum of depressives, extending more widely into anxiety disorders, panic disorder, and obsessive-compulsive disorder. Tricyclic use has lessened in recent years in favour of antidepressants with fewer side effects.
Serotonin and noradrenaline reuptake inhibitors 
(SNRIs).  Selective SNRIs share the proposed therapeutic mecha-
nisms of tricyclics but with fewer and different side effects, includ-ing the serotoninergic effect of nausea, and for venlafaxine at high dose, risk of blood pressure elevation and cardiac arrhythmia, 
with toxicity in overdose. There is good efﬁ  cacy evidence for 
venlafaxine, with possible superiority over SSRIs,
(3) and emerging

(3) and emerging 
evidence for duloxetine.(4) A further SNRI in some countries is 
milnacipran.
Selective serotonin reuptake inhibitors (SSRIs).  Meta-analyses 
of SSRIs(5) show efﬁ  cacy comparable with tricyclics, but lower rates 
of side effects and discontinuation. There is conﬂ  icting evidence 
as to whether SSRIs are less effective than tricyclics and SNRIs in severe depression. SSRIs and clomipramine, the most serotoninergic tricyclic, are more effective than noradrenergic tricyclics in obsessive-compulsive disorder.
There have been vigorous debates regarding effects of antidepres-
sants, particularly SSRIs, on suicidal behaviour, with many stud-ies.
(6) Actual suicide does not appear to be increased and may be

(6) Actual suicide does not appear to be increased and may be 
reduced. There is some evidence that suicidal feelings and attempts may be increased in the early weeks after starting, particularly for SSRIs, with development of tension or agitation, and in children and adolescents. On the other hand SSRIs and other newer antide-pressants are considerably safer in overdose than tricyclics and SNRI. 
Warnings were issued by regulatory authorities in the United States and the United Kingdom when the evidence started to emerge. Most 
strongly the ﬁ  ndings argue for careful clinical surveillance of patients 
prescribed antidepressants, particularly in the early phases of
treatment when risk of suicidality has long been recognized as 
increased. This is in any case important in depressed patients.

Noradrenaline reuptake inhibitors.  Only one newer selective 
NARI is available, reboxetine. It is clearly superior to placebo.
(7)
(iii) Monoamine oxidase inhibitors (MAOIs)
Irreversible MAOIs.  There are few MAOIs available, reﬂ  ecting 
hypertensive and other interactions and limited use. The older MAOIs bind irreversibly to the enzyme, and new enzyme needs to be synthesized over 1–2 weeks to reverse the effect. Controlled trials
(8) show superiority to placebo in depression, and in anxiety 
disorders. Often high doses are necessary and the hydrazine MAOIs, phenelzine, and isocarboxazid, show better clinical response in slow acetylators. Tranylcypromine has additional stimulant effects, and has been viewed as more effective but with more risk of interactions.

From the late 1950s, there were suggestions of particular efﬁ  cacy 
in atypical depression, variously regarded as non-endogenous depression, anxiety disorder with depression, or as a pattern of reversed vegetative symptoms with increased appetite, increased sleep, evening worsening, reactivity, and other features, a meaning currently predominant in the United States. Evidence is not strong, but comparative trials of phenelzine and tricyclics point to better effects than tricyclics with anxiety disorders and reversed vegetative 
symptoms.
(8) On the other hand MAOIs are mostly used as 
second-line drugs by psychiatrists, where other antidepressants 
have failed, irrespective of clinical picture.
Reversible competitive inhibitors.  The reversible MAO-A selec-
tive drug moclobemide can dissociate from the enzyme and be displaced by substances with higher afﬁ  nity, including tyramine. 
It shows superiority to placebo,
(9) but not at doses below 450 mg

(9) but not at doses below 450 mg 
daily, and evidence is best for 600 mg. Many clinicians view moclobemide as less effective than older MAOIs.Table 4.5.8.1  Antidepressant medications*
Drug Usual dose range 
(mg/day)**
Reuptake inhibitors
Tricyclics
Amitriptyline  75–300
Clomipramine  75–300
Desipramine  75–300
Dosulepin (dothiepin)  75–225
Doxepin  75–150
Imipramine  75–300
Lofepramine  70–210
Nortriptyline  75–150
Proptriptyline  15–60
Trimipramine  75–300
Serotonin and noradrenaline reuptake inhibitors (SNRIs)
Duloxetine 60Venlafaxine  75–375 (check)
Selective serotonin reuptake inhibitors (SSRIs)
Citalopram  20–60
Escitalopram  10–20
Fluoxetine  20–80
Fluvoxamine  50–300
Paroxetine  20–60
Sertraline  50–200
Selective noradrenaline reuptake inhibitor (NARI)
Reboxetine  4–12
Monoamine oxidase inhibitors

Irreversible monoamine oxidase inhibitors
Isocarboxazid  30–60
Phenelzine  45–90
Tranylcypromine  20–30
Reversible monoamine oxidase inhibitor (RIMA)
Moclobemide 300–600
Others
Bupropion 200–450
Mianserin  30–90
Mirtazepine  15–45Trazodone 150–600
*This list is not fully comprehensive because of new developments and national differences.
**Ofﬁ  cial dose recommendations vary between countries and should always be checked.

671
(iv) Other antidepressants
Bupropion.  Bupropion is relatively stimulant and is epileptogenic. 
It is licenced for depression in the United States, and in some other countries as an aid to smoking cessation.
Mianserin.  Mianserin, an older drug which blocks alpha-2 auto-
receptors, is sedative in side effects and carries a deﬁ  nite although 
low risk of agranulocytosis.
Mirtazepine.  Mirtazepine blocks alpha-2, 5HT2, and 5HT3 
receptors. It has been shown superior to placebo and is also a sedative.
(10)
Trazodone.  Trazodone, an older drug is relatively sedative carries 
a risk of priapism in males.
New classes of antidepressants, not yet licenced, are continually 
being sought.(11) Agomelatine, an agonist at melatonin MT1 and 
MT2 receptors and a 5HT2C antagonist has shown evidence of efﬁ cacy. Efforts have been made to develop drugs, which inhibit

MT2 receptors and a 5HT2C antagonist has shown evidence of efﬁ cacy. Efforts have been made to develop drugs, which inhibit 
cortisol secretion. Development pathways for new antidepressants are long and failures due to weak treatment effects or major adverse effects are common.
(b) Electroconvulsive therapy (ECT)
ECT, the earliest of modern treatments, is still the most effective in severe depression. In a meta-analysis.
(12) It has been found more 
effective than simulated ECT in blind trials, and more effective than pharmacotherapy. Bilateral ECT appears more effective than unilateral but this may not be true at adequate stimulus intensity. Best effects occur in psychotic depression with delusions or psy-chomotor retardation. There is also some evidence, which is not conclusive, that ECT may beneﬁ  t mania.
Other physical treatments
(a) Bright light

Bright light, reviewed in Chapter 6.2.10.2 is the established treatment 
for seasonal affective disorder. Several studies in non-seasonal depressions as adjunctive treatment have suggested some beneﬁ  t, 
although the effect may not be sustained.
(13)
(b) Repetitive transcranial magnetic stimulation (TMS)
TMS is reviewed in Chapter 6.2.10.3. There is clear evidence of superiority of left prefrontal TMS compared with sham therapy but the degree of beneﬁ  t appears weak. There is still uncertainty 
regarding optimal stimulation parameters. At present theevidence is not sufﬁ  cient for widespread use of TMS in clinical 
practice.
(c) Vagus nerve stimulation
Stimulation of afferent left cervical vagus nerve ﬁ  bres by a stimula-
tor implanted in the chest wall is approved by regulatory authori-ties in a number of countries for resistant epilepsy and in the United States for resistant depression. Controlled evidence is still limited.
(14)

(14)
(d) Deep brain stimulation
Chronic stimulation of white matter tracts adjacent to the sub-genual cingulate region by implanted electrodes has been report-ed to produce striking remission in a small number of patients with resistant depression, associated with marked reduction in local cerebral blood ﬂ  ow.
(15) Further experience is still needed.Longer-term treatment
(a) Continuation treatment
In recent years, it has become apparent from follow-up studies that 
the long-term outcome of depression is still often problematic. It is customary to distinguish between relapse, or early symptom return, and later recurrence of a new episode.
(16) In parallel, drug treat-
ment after the acute episode has been divided into earlier continu-ation treatment, to prevent relapse, and longer-term maintenance treatment to prevent recurrence.
There have been many controlled trials of continuation treat-

ment on active drug for 6 to 8 months after the acute episode against withdrawal to placebo, showing substantial beneﬁ  t from 
continuation.
(17) A ﬂ uoxetine study with staged withdrawal showed 
beneﬁ  t of continuation for 24 and 38 weeks, but not 62 weeks, 
suggesting that routine continuation should be for 9–12 months rather than 6 months.
(18) A controlled trial of early lithium with-
drawal after augmentation showed very high relapse rate indicating a need for lithium continuation
(19) and there is evidence for 
continuation drugs after ECT.
(b) Maintenance treatment
Longer-term studies in unipolar depression have shown clear beneﬁ  t from maintenance antidepressants,
(17) although recurrence 
rates in drug-treated patients may be high.
Withdrawal reactions requiring temporary restarting can occur

Withdrawal reactions requiring temporary restarting can occur 
if antidepressants are stopped abruptly, particularly after high doses for long periods, with malaise, coryza-like symptoms, vomiting, and diarrhoea. This may occur with a variety of antidepressants including SSRIs, tricyclics, and SNRIs.
Trials of lithium in maintenance treatment of severe recurrent 
unipolar depressives also show beneﬁ  t over placebo.
(20) Comparative 
efﬁ cacy against antidepressants is not clear.
(c) Acute treatments for bipolar disorder
In the treatment of bipolar depression there is a good evidence 
for efﬁ  cacy of antidepressants.(21) The major risks are precipita-
tion of mania and rapid cycling, which appear to occur morewith tricyclics and venlafaxine than with other antidepressants, suggesting the preferential use of SSRIs, MAOIs, or ECT andcovering with lithium. Lamotrigine has also been foundeffective.

(22) For lithium alone as an antidepressant the evidence 
is less clear-cut.
In the treatment of acute mania, lithium has been extensively 
reviewed and the evidence is good.(23) Anticonvulsants have been 
increasingly evaluated, with good controlled trial evidence in mania 
for valproate and carbamazepine, but not lamotrigine or other anticonvulsants.
(22) There is also controlled trial evidence for anti-
psychotics, both older and newer.(24) Available trials do not clearly 
point to choice of treatment.
(d) Maintenance treatment of bipolar disorder
Controlled trials of maintenance lithium against placebo in bipolar disorder show clear reduction of recurrences, particularly of mania, with weaker effects on depression.
(25) There is also reduction of 
suicide in mood disorder more generally.
There are high rates of early recurrence, particularly of mania, 
when lithium is discontinued after long-term use, particularly if discontinuation is rapid.
(26) This mandates slow withdrawal in

(26) This mandates slow withdrawal in 
practice. One study.(27) has indicated greater beneﬁ  t on residual 4.5.8 treatment of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 672
symptoms for doses producing blood levels 0.8 to 1.0 mmol/l 
than for 0.4 to 0.6 mmol/l. This is important since follow-up studies of bipolar patients show that subsyndromal symptoms are common.
There have been fewer long-term studies of anticonvulsants.
(22)
For valproate evidence is suggestive rather than conclusive. For lamotrigine two controlled trials have conﬁ  rmed prophylaxis of 
bipolar depression. Although carbamazepine has been used for longer, evidence from placebo-controlled trials is mainly for acute treatment of mania.
Several manufacturer-sponsored trials have indicated
prophylactic effects of olanzapine in maintenance. Older anti-psychotics have long been used as adjunctive treatment inbipolar maintenance.
Psychological treatments

There is high public demand for psychotherapies. Guidelines are less well developed and less robustly based than for pharmaco-therapy. The concept of empirically supported psychotherapies (EST) assists deﬁ  nition of the evidence base.
(28)
(a) Acute treatment of depression
(i) Psychological treatments: general issues
The therapy models can broadly be divided into ‘process-orientated’

(28)
The therapy models can broadly be divided into ‘process-orientated’ 
therapies such as psychodynamic or supportive–expressive thera-pies, and ‘outcome-orientated’ therapies, such as cognitive behav-iour therapies (CBT) and interpersonal therapy (IPT), which primarily focus on symptom reduction. The latter EST are protocol or guideline driven, with a manual describing the therapy in detail. In large-scale randomized controlled treatment trials (RCTs) they have been found superior to pill or psychological placebo-controlled treatments or efﬁ  cacious as antidepressants or other 
established treatments.
(28) The EST are usually brief (12–20 sessio ns), 
delivered by a trained therapist, establishing a working alliance and using an individualized case formulation to focus on speciﬁ  c 
‘here and now’ problems, encouraging between session ‘homework’ tasks to enable development of new coping skills.

(ii) Meta-analyses
The two best-evaluated therapies are CBT (including behaviour therapies) and IPT, with many meta-analyses of a large number of RCTs. There are fewer studies of dynamic therapies. Early outcome studies and resultant meta-analyses were hampered by use of ‘completer’ samples rather than ‘intent-to-treat’ analyses, but found speciﬁ  c psychological therapies, particularly CBT, more effective 
than other verbal therapies or waiting-list controls. A meta-analysis of 29 carefully selected controlled trials,
(29) using intent to treat 
analyses, found efﬁ  cacies of individual CBT (response rate, 50 per 
cent), behavioural therapy (55 per cent), and IPT (52 per cent) in the treatment of the acute episode were not signiﬁ  cantly different

cent), behavioural therapy (55 per cent), and IPT (52 per cent) in the treatment of the acute episode were not signiﬁ  cantly different 
to pharmacotherapy (58 per cent). Brief dynamic psychotherapies, mainly group therapies, were less effective (35 per cent) and only marginally superior to waiting-list controls (30 per cent). CBT was less effective in a group format, behavioural therapy was equally effective, and IPT was more beneﬁ  cial when a signiﬁ  cant other took 
part in therapy.
A recent meta-analysis
(30) found CBT and IPT equally effective 
in reducing depressive symptoms in heterogeneous groups of patients with depressive symptoms and syndromes, and both were superior to counselling, other therapies or control treatments 
in primary care. When compared in meta-analyses to an active treatment, however, CBT and IPT show only equivalent efﬁ  cacy or

in primary care. When compared in meta-analyses to an active treatment, however, CBT and IPT show only equivalent efﬁ  cacy or 
marginal superiority. Almost all RCTs of psychological therapies have been in outpatient depressives, not above moderate severity and comparisons with pharmacotherapy do not represent severe or inpatient disorder.
(iii) Cognitive therapy
Earlier CBT studies suggested it was effective over a range of sever-ity and endogenicity. However, in the three-centre NIMH study,
(31)
which sought to overcome earlier methodological ﬂ  aws, a second-
ary analysis found CBT less effective than pharmacotherapy in the more severe disorders within the outpatient range studied. Another study found that individuals with mild or moderately severe depression did equally well with either 8 or 16 sessions, but those with severe depression showed better response with 16 sessions. A large RCT in subjects with severe major depressive disorder
(32)

(32)
found no difference overall between antidepressants and CBT, but also signiﬁ  cantly greater effects for antidepressants at the trial 
centre where the CBT therapists were less experienced.
(iv) IPT
IPT Has been found effective in moderate numbers of RCTs, in a variety of situations, including combination studies with antide-pressants and some situations where medication as a ﬁ  rst-line 
treatment for depression is not easily feasible (pregnancy, postpar-tum, adolescence, and in a developing country).
(33) The NIMH 
study(31) is the only one that has compared IPT with a pill-placebo 
control. Interpersonal therapy was nearest to the effectiveness of imipramine but a little weaker, and IPT was more beneﬁ  cial than 
CBT in patients with more severe outpatient depression.
(v) Other psychotherapies

Fewer acute controlled trials of other therapies have been published. Two large-scale RCTs of individual behavioural therapy found respectively greater efﬁ  cacy than insight-orientated therapy, 
which disappeared by 3 months follow-up, and no differences from several other treatments.
The only published RCTs on marital therapy mainly draw on 
behavioural approaches with behavioural marital therapy or CBT both more effective than waiting-list controls in one study and an advantage for behavioural marital therapy over CBT one study of depressed individuals with marital discord. Couples therapy was more effective than pharmacotherapy in a study of depressed patients living with a critical partner. An RCT of family therapy in inpatients with affective disorder
(34) found beneﬁ  t on role function 
for female patients on discharge, and for bipolars but not unipolars on follow-up.

Counselling is often offered alone or in combination with 
medication, particularly in primary care or non-specialist mental health settings. Recent meta-analyses
(30) suggest limited beneﬁ  ts, 
with superiority over treatment as usual or waiting-list control conditions lost beyond about 3 months. Individuals who are socially isolated and lack a conﬁ  dante may particularly beneﬁ  t.
(vi) Combined psychotherapy and pharmacotherapy
Data on whether combination of psychotherapy and pharmaco-
therapy bestows additional beneﬁ  t over either treatment alone are 
not conclusive, but some studies suggest a small advantage at the

673
level of severity usually studied, both for CBT and for IPT. However, 
in a meta-analysis of eight outcome studies, neither CBT, behav-ioural therapy, nor IPT added to antidepressants were any more effective than pharmacotherapy alone.
(35)
In a large RCT of antidepressant and cognitive behavioural anal-
ysis system of psychotherapy (CBASP) given alone, or in combina-tion for major depressive episode persisting for longer than 1 year
(36) the group receiving the combined treatment had signiﬁ  -
cantly greater overall reduction in depressive symptoms and attain-ment of remission as compared with single therapies.
In other studies, treatment with an antidepressant alone or in 
combination with IPT has been found more effective than IPT alone in dysthymics, and greater beneﬁ  t of combined treatment has

combination with IPT has been found more effective than IPT alone in dysthymics, and greater beneﬁ  t of combined treatment has 
been reported in an RCT of group CBT and medication. These studies indicated that combined treatments improved quality of life over and above individual treatments. There is also some evidence that social adjustment is particularly beneﬁ  ted by IPT.
(b) Longer-term psychological treatment
(i) Continuation and maintenance trials
Psychological treatments are more expensive than antidepressants, 
but the balance could change if they reduced relapse rates.(37)
Naturalistic follow-ups suggest this, but are hard to interpret because the original RCTs were not designed or powered to evaluate long-term outcome.
The use of continuation and maintenance psychotherapy is a 
relatively new concept. The key maintenance trial for IPT
(38)

(38)
assigned subjects with recurrent depression to imipramine,placebo, or monthly IPT with or without medication. Therewas a highly significant effect for antidepressants on recurrence rates and a modest effect (at the end of year 1 and year 3)for IPT. The first study of IPT, by its originators 15 years earlier, did not find it reduced relapse, compared with antidepressant continuation.
Five longer-term RCTs have now shown relapse and recurrence 
reduction with CBT.
(37) Three of these, in individuals in remission 
using mindfulness or other techniques have only found beneﬁ  t in 
subjects with a previous history of repeated episodes.
At least 20 per cent of people with an initial episode of major 
depressive disorder do not recover within 2 years, and those with residual depressive symptoms have a high risk of relapse. In a RCT

(39) in 158 subjects with persistent residual depressive 
symptoms following major depression assigned to antidepressant continuation or antidepressant plus CBT, at 18-month follow-up relapse rates in the CBT plus antidepressant group were reduced by 45–50 per cent compared with the control group. Relapse pre-vention persisted for 3.5 years. Similar ﬁ  ndings have been obtained 
in three small RCTs.
(40)
(c) Bipolar disorder
Until very recently, research in psychological treatments for bipo-lar disorder was limited. Prior to 1995 a number of small studies, few of them randomized trials, suggested that adherence tomedication was improved.
(41) More recently good RCTs have been 
completed. The earlier of these found some beneﬁ  t from psycho-

logical treatments in preventing relapse, with a hint that thebriefer interventions are more effective in preventing mania than depression. A meta-analysis of relapse rates
(42) found an odds 
ratio (OR) for relapse in the intervention as compared to thecontrol group of 0.31. Three recent large efﬁ  cacy trials used CBT, family therapy, or group psycho-education, respectively. A sepa-
rate meta-analysis of these
(42) found a similar odds ratio for 
relapse, with more beneﬁ  t for depressive than manic/hypomanic 
relapses.
The MRC multicentre RCT in the United Kingdom(43) was

relapses.
The MRC multicentre RCT in the United Kingdom(43) was 
one of the few pragmatic effectiveness trials, with over 250 sub-jects randomized to CBT plus usual psychiatric treatment or usual treatment alone. Over 50 per cent of the sample had a recurrence by 18 months, with no overall significant differences between groups, but a significant interaction with number of previous episodes such that CBT was significantly more effec-tive than treatment as usual in subjects with fewer than 12 pre-vious episodes, but less effective in those with more episodes.
One variant of IPT has been evaluated in a large RCT, interper-
sonal and social rhythm therapy (IPSRT), which includes an approach to stabilize social rhythms.
(44) It was found to reduce

(44) It was found to reduce 
bipolar relapse rates more than did IPT. The full advantages and disadvantages of different forms of psychotherapy for bipolar disorders are yet entirely clear, but further evidence is expected to emerge soon.
Treatment of unipolar disorder
(a) General aspects: where to manage
The goals of depression treatment are to alleviate acute symptoms, to restore psychosocial functioning, and to prevent relapse and recurrence. Crucial decisions are the selection of an intervention and treatment setting. These involve four key issues: severity of the disorder including risk of self-harm, availability of treatments (speciﬁ  c antidepressants, trained therapists), patient preference, 
and nature of any associated difﬁ  culties. Recent guidelines include

and nature of any associated difﬁ  culties. Recent guidelines include 
those of the UK National Institute for Health and Clinical Excellence
(45) and of CANMAT.(46)
(b) Treatment setting
Very severe depression with deﬁ  nite suicidal risk is best managed in 
inpatient facilities to allow careful monitoring. With less suicidal risk and good social support severe cases can be managed with intensive community support, partial hospitalization, day care, or combined outpatient and home-based care. Moderate or mild depression should be managed in outpatient settings, unless treat-ment is complicated by severe physical illness, or non-response requires more detailed assessment.
(c) Primary or secondary care
Worldwide, most depressed patients are treated in primary care or general medical settings. Cases are referred to specialist mental health services because the disorder is more severe, chronic, treat-ment resistant, or because other difﬁ  culties, such as alcohol misuse

or marital problems, complicate the clinical picture.
(d) Medication or psychological therapy
Although severe depression may respond to psychotherapy alone, recovery is slower than with drugs or ECT. Psychotherapy may be used in addition, rather than alone. In milder depressions, choice depends partly on patient preference and availability of psycho-therapies, although when major depression criteria are reached antidepressants should preferably not be withheld. In the complex situations requiring specialist referral it is often necessary to use 4.5.8 treatment of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 674
combinations of drugs and psychosocial approaches. Although 
physical and psychological treatments are described separately in this section, treatment rarely involves only prescribing, but educa-tion and support of patient and family are important aspects of any clinical management.
(a) When to treat
The most important indications for use of medication are severity and persistence. A severity threshold has been shown a little below major depression at which tricyclic antidepressants start to show superiority over placebo.
(47) SSRIs may show beneﬁ  t in minor 
depression.(48) Antidepressants are also superior to placebo in dys-

thymia. In mild depressive episodes highly reactive to major stress, and in acute grief, prognosis for spontaneous resolution is often good, and medication may be delayed, provided that improvement is occurring. Impairment of function and suicidal feelings are other indications to treat. Recent guidelines recommend use in depres-
sion of moderate severity, major depression, or ICD-10 depressive 
episode.
(b) What antidepressant to choose
Since SSRIs are comparatively free of side effects and are not costly if out of patent, they are generally recommended as ﬁ  rst choice 
antidepressants. Where there is a previous history of response to a speciﬁ  c drug or class, the best ﬁ  rst choice is that antidepressant.
With few exceptions, symptom pattern is not a good guide to

With few exceptions, symptom pattern is not a good guide to 
treatment. Effects of antidepressants extend widely across the spectrum of depression and in to anxiety disorders. The place of SSRIs in very severe depression is still debated. MAOIs or SSRIs or are a reasonable ﬁ  rst choice in atypical depression. With comorbid 
obsessive-compulsive disorder the SSRIs, SNRIs, or clomipramine are preferable to noradrenergic antidepressants. Light therapy is indicated for seasonal affective disorder, alone or with antidepressant.
(c) How to use an antidepressant
There is a delay in clinical antidepressant effects of 1 to 3 weeks or longer, although some improvement may be seen earlier. An anti-depressant needs to be continued for a minimum duration of 6 weeks at adequate or high dose before being regarded as ineffective.
Since side effects often occur more in the early weeks, with later 
tolerance, build-up of dose over 2 to 3 weeks is useful. For ﬂ  uox-

etine, the exceptionally long half-life of the active metabolite means that blood levels build-up for some weeks, even on a standard dose. Standard dosage regimes fail to allow for the considerable interin-dividual variability in pharmacokinetic mechanisms that occurs. Low doses are usually ineffective. Where response is not occurring and there are only minor side effects doses should be increased towards maximum, except in the elderly, who are vulnerable to 
poor elimination and to side effects.
Dose division during the day can be based on pharmacology.

Dose division during the day can be based on pharmacology. 
Half-lives of most antidepressants, combined with delay in thera-peutic effects, mean that one dose per day may be adequate, but for most, two doses per day are better and three doses may be useful for some patients. Moclobemide, which is easily displaced from MAO and metabolized, should be given in three doses daily. For sedative antidepressants, administration of two-thirds of the dose at night may avoid hypnotics. Doses at bedtime of the more 
stimulant antidepressants, including SSRIs and older MAOIs, should be avoided.
Common side effects of SSRIs and SNRIs are nausea, and other

Common side effects of SSRIs and SNRIs are nausea, and other 
gastrointestinal disturbances, insomnia, and sometimes tension and restlessness. Blood pressure should be monitored with high dose venlafaxine and it should not be used with hypertension or risk of ventricular arrhythmias. Common side effects of tricyclics clinically are sedation and anticholinergic side effects of dry mouth, blurred near vision, urinary retention, orthostatic hypotension, and confusion in the elderly. Dose-limiting side effects of MAOIs are hypotension, insomnia, and ankle oedema and tyramine containing foods and interacting drugs must be avoided.
(d) What to use if the ﬁ  rst choice does not work
The evidence base for second choice of antidepressant after 
poor response to the ﬁ  rst is weak. The large non-blind partially 
randomized STAR*D study,(49) has shown few differences between

randomized STAR*D study,(49) has shown few differences between 
different choices after weak ﬁ  rst response to citalopram.
The major pragmatic options are switch to a different antide-
pressant or combination. Switch should be to an antidepressant of a different class, or to a broad action SNRI. If this is not adequate, lithium augmentation is the best-supported change. Where depres-sion is severe ECT is an alternative second choice.
(e) What to use in special situations
(i) Suicidal risk
Major suicidal risk requires consideration of lethality of particular antidepressants in overdose. Tricyclics and SNRIs should be avoided. SSRIs and most other newer antidepressants are comparatively safe in overdose, with careful monitoring for increased risk early in treatment.
(ii) Psychotic depression

Evidence as to choice of antidepressant is weak, but suggests SNRIs or tricyclics, rather than SSRIs. Combination with an antipsychotic may be useful, but antipsychotics are not adequate alone.
(50) ECT is 
an alternative.
(iii) Medical illness
Antidepressant treatment with medical disorders is often difﬁ  cult, 
because of toxicity due to illness, high blood levels from impaired metabolism, side effects, and drug interactions. Cardiac problems indicate use of an SSRI or other newer non-tricyclic non-SNRI antidepressant, and treatment after myocardial infarction may enhance survival. MAOIs lower blood pressure as a dose-related effect and should be avoided.
Concomitant epilepsy may be controlled by adjustment of

Concomitant epilepsy may be controlled by adjustment of 
anticonvulsant dose. Tricyclics and bupropion are epileptogenic and should be avoided. Epileptic potential is usually less with newer antidepressants but is often not clear, and the only antidepressants established not to be epileptogenic are older MAOIs.
(iv) The elderly
The elderly are particularly liable to side effects. SSRIs and newer antidepressants are preferable to tricyclics.
(v) Children
Antidepressants are not ﬁ  rst choice treatments for depression in 
children and adolescents, for whom psychological therapy is pref-erable. Where the depression is not improving and is severe, an

675
antidepressant may be needed. Tricyclics are not effective.(51) There 
is more evidence for SSRIs, best for ﬂ  uoxetine,(52) but the risk-
beneﬁ  t ratio is argued. For adolescents combination of SSRIs with 
CBT may be useful. The risk of increased suicidality early in treat-ment mandates careful observation. The FDA issued an Advisory in 2004 but not a contraindication.
(vi) Pregnancy and lactation

Tricyclics have been used in pregnancy for many years and do not carry risk of foetal malformation. For SSRIs the current evidence is contradictory and for some newer drugs evidence is lacking. Lithium and anticonvulsants carry some risk of foetal malforma-tion and are contraindicated in the early months of pregnancy. Psychotropic drugs used at the time of delivery may produce com-plications of anaesthesia and foetal sedation and if possible should be withdrawn temporarily. Most psychotropic drugs appear in breast milk in small quantities. Breast feeding should be discussed with the patient.
Electroconvulsive therapy
Use of ECT varies internationally. Many psychiatrists use it as aﬁ rst choice treatment in severe depression with psychomotor

Use of ECT varies internationally. Many psychiatrists use it as aﬁ rst choice treatment in severe depression with psychomotor 
retardation or mood-congruent depressive delusions, or wherean antidepressant has failed, and for moderately severe depressions which have not responded to one or two courses of antidepressant.
The UK National Institute for Clinical Excellence has recom-
mended use only to achieve rapid improvement where a trial of other treatment has failed or the condition is potentially life threat-ening, in severe depression, catatonia, and prolonged or severe mania.
(53) Detailed recommendations on how ECT should be 
administered also can be consulted.(54)
Non-response and resistant depression
Controlled trials of treatments for depressives who do not respond to ﬁ rst or second treatments are limited. There is good evidence for 
lithium augmentation of antidepressants
(55) and limited evidence

(55) and limited evidence 
for potentiation by triiodothyronine (T3).(56) A variety of other 
augmenters have been tried including tryptophan, pindolol,  bus-pirone, and combinations of antidepressants such as SSRI-bupro-pion, SNRI-mirtazepine, tricyclic-MAOI, with weak evidence.
We therefore depend on clinical experience.
(57) If there is still 
limited response after several antidepressant treatments, a system-atic approach to resistant depression should be adopted:
1 Reassess the situation thoroughly, with full history, assessment,

1 Reassess the situation thoroughly, with full history, assessment, 
and laboratory investigation of thyroid function to ask the fol-lowing questions: (a) Is the diagnosis correct? Wrong diagnosis is in practice unusual. (b) Are there perpetuating factors in person-ality, family environment, or the social setting? Commonly, where depression has been long-term, secondary role loss (including work), and family adaptations to a non-functioning member mean there are no roles or relationships for the patient to return to and remission cannot occur, or is transient, unless psychotherapy, family therapy, and rehabilitation are employed to change the situation. (c) Is hypothyroidism impairing response? This may develop as a result of earlier use of lithium.
2 Consider previous treatment. Failure to use high or maximal

2 Consider previous treatment. Failure to use high or maximal 
doses of antidepressants when response is not occurring can lead to apparently resistant depression.3 Employ drug and other physical treatments.
4 As remission occurs, introduce psychotherapeutic, cognitive, and 
rehabilitative interventions.
The treatment decisions depend on what has been used before. 
Start with the most promising antidepressant suggested by the history and push to a very high dose. If there is no good clue venlafaxine may be useful, with monitoring of blood pressure for elevation as high doses are reached.
The next intervention is augmentation. Lithium is easiest 
and best. Blood levels required for augmentation are not estab-lished. If response occurs, the lithium should be continued for some months, although not as long as antidepressant. Care should be taken to monitor for a serotonin syndrome (excitability, restless-ness, temperature elevation), with serotoninergic antidepressants.

T3 may produce fewer side effects than lithium but evidence is 
weaker and care must be exercised if there are cardiac problems. L-tryptophan may potentiate MAOIs and the more serotoninergic uptake inhibitors. Its effect is weak, but may be combined with lithium. Pindolol, which blocks 5-HT
1A autoreceptors, can
accelerate speed of antidepressant response but increased amount of response is less clear.
At one time tricyclic-MAOI combinations were often used and 
occasionally still have a place, combined with lithium. SSRIs, SNRIs, and clomipramine risk of serotonin syndrome and are contraindi-cated. Doses should be increased gradually. More ordinarily 1 to 2 weeks should intervene between stopping an older MAOI and starting a reuptake inhibitor.
When vigorous medication regimens have still not produced a

When vigorous medication regimens have still not produced a 
response, it is often helpful to add bilateral ECT to maximal drug therapy, even when ECT alone has not previously helped. The practical places for vagus nerve stimulation and deep brain stimu-lation are not yet clear. In intractable severe chronic depression, psychosurgery still has an occasional place, followed by active 
rehabilitation.
Longer-term treatment
(a) Continuation treatment: a routine
Continuation antidepressant for 9–12 months should be routine 
following response to acute treatment. Antidepressant or lithium are also advisable after ECT. The continuation dose should initially be the same as the acute treatment dose. After 2 to 3 months this may be reduced if side effects are a problem, but only by a small amount, to avoid symptom return.
Before the antidepressant is withdrawn the patient should also

Before the antidepressant is withdrawn the patient should also 
be completely free of residual symptoms for at least 4 months. These symptoms or history of previous relapse or recurrence suggest longer continuation. Withdrawal should then be carried out slowly, over 2 to 3 months, to minimize the risk of relapse, and of withdrawal symptoms.
In some patients, after withdrawal, or achievement of a low dose, 
depressive symptoms return. Full dose should be resumed, fol-lowed by continuation for a further period of 9 months to a year. 
Some of these patients relapse again on later drug withdrawal, and 
long-term maintenance should then be considered.
Longer-term maintenance is indicated where there have been several recurrences, such as two episodes in the last 2 years, or three 4.5.8 treatment of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 676
episodes in 5 years.(16,45)  This also depends on the severity of 
episodes, their potential impact on personal life, family life, and career, and the patient’s preferences. Discussion is required, to reach a joint decision.
For most unipolar depressives the maintenance treatment choice 
will be whichever antidepressant has been effective and well tolerated. Where antidepressants have not been fully effective, lithium or combination are required. Antidepressant doses should be the same or a little lower than those needed for acute treatment in the particular patient. The length of maintenance is harder to specify, and it depends on the history. Two to three years will be a mini-mum, longer where remission has been difﬁ  cult to achieve or 
recent episodes more frequent, 5 years or more where risk is greater, and indeﬁ  nite or lifelong where two or three attempts to 
withdraw have been followed by another episode within a year.
(16)

(16)
Withdrawal of antidepressants, lithium, or other drugs after long-term maintenance should always be gradual. Where withdrawal is followed soon after by a recurrence, longer-term maintenance is indicated, and where this sequence has been repeated, lifelong treatment.
The psychological management of acute depression ranges across basic clinical management, psychoeducation for the individual and partner or family, supportive psychotherapy, to formal psychotherapy.
(a) Clinical management

Clinical management is a key component of the care of all indi-viduals with depression regardless of the specific treatment. It includes education about the nature of the disorder, its polarity, course and prognosis, treatment options, their advantages and disadvantages, delay in beneﬁ  ts, probable side effects and how to 
manage these, and planned length of treatment. This dialogue can help build a strong treatment alliance, overcome misconceptions such as fears of addiction to antidepressants, and improve medica-tion adherence. Involving ‘signiﬁ  cant others’ also in some sessions 
facilitates information and engagement in the treatment process, clariﬁ  es what aspects of care are the clinician’s responsibility, and 
can help reduce tension in interpersonal relationships resulting from the patient’s depression. For many depressed individuals the reduction in symptoms from this basic approach and medication

can help reduce tension in interpersonal relationships resulting from the patient’s depression. For many depressed individuals the reduction in symptoms from this basic approach and medication 
restores the previous level of functioning. They are again able to 
use their coping skills to resolve personal problems and no other form of psychological input is needed.
(b) When to use psychological therapies
If additional strategies are needed, a number of factors should guide their choice, including treatment setting, severity, chronicity, complexity, patient preferences, and availability of therapists. Most management approaches are multifaceted and in a dynamic state so the divisions below, structured by severity of depression, although useful may be somewhat artiﬁ  cial.
(i) Mild depression
For individuals with milder depression, usually treated in primary

For individuals with milder depression, usually treated in primary 
care, psychological approaches can be used alone as alternatives to medication, and there is little advantage in combined treatment. Many patients express their own treatment preferences. Some primary care physicians offer extended treatment sessions fordepression, but many utilize counsellors. A course of counselling, 
lasting 8–10 sessions, is particularly useful to patients who lack a con-ﬁ dante. Beneﬁ  ts appear in the ﬁ  rst 3 months, but there is no evidence 
of longer-term beneﬁ  ts compared to other treatments or ‘watchful 
waiting’
(45) (regular appointments with a clinician offering monitor-
ing and support without medication or other interventions).
The next option may be CBT or IPT. There are no robust predic-
tors of differential response to these as opposed to medication so choice often depends on availability of a suitable therapist. Difﬁ  culties

tors of differential response to these as opposed to medication so choice often depends on availability of a suitable therapist. Difﬁ  culties 
in timely access have led to development of computerized CBT and of self-help approaches. The individual is offered a computer version of therapy or a written manual to guide self-therapy (bibliotherapy), with possible 1–3 sessions from a therapist to explain the process and overcome hitches. In other circumstances, including management of depressed pregnant women, telephone versions of IPT have been developed. There is not yet consensus on the efﬁ  cacy of these alterna-
tives but a trial may be used in mild depression.
(ii) Moderate depression

Formal psychotherapy may be offered to individuals with moder-ate depression as the only treatment, or preferably combined with medication. Usually this comprises 15–20 sessions of individual therapy, but since more than 20 per cent of couples report mari-tal discord in association with depression, marital or family approaches should also be considered. Psychological treatments may also be required where medical conditions or needed medi-cations contraindicate antidepressants, or the patient refuses medication. Other important considerations include previous coping skills, premorbid stressors requiring problem-solving approaches, ability to articulate emotions and difﬁ  culties. If there 
are doubts regarding suitability, referral may be offered for assessment. Patient preference for therapy does not imply bene-ﬁ t, and dropout rates are about similar to those for medication.

are doubts regarding suitability, referral may be offered for assessment. Patient preference for therapy does not imply bene-ﬁ t, and dropout rates are about similar to those for medication. 
Also consider whether needs can be met through a time-limited 
input or if longer-term support is preferable through day servic-es or a community support worker. Therapists adherence to the therapy model, their level of expertise and skill and the provision of regular and adequate supervision to the practitioner are other factors and may account for some 30 per cent of the variance in patient’s improvement.
(58)
(iii) Severe depression or complex presentations
Research evidence suggests that CBT or IPT may be used alone in severe depression if delivered by an expert therapist. However improvement is slower than with antidepressants and in practice these are usually combined with medication, which is commenced ﬁ rst. In severe depressions it may be difﬁ  cult for an individual to

concentrate until the mental state has been stabilized by medica-tion. Patients who fail to respond adequately to antidepressants alone require reassessment. In many instances medication has improved the vegetative symptoms of depression, but the individual manifests psychological vulnerabilities, such as Axis II comorbidity or long-standing, low self-esteem, or social stressors, acting as maintenance factors and amenable to therapy. The evidence sug-gests that IPT or CBT are the most useful therapies to combine with antidepressants in unipolar disorders, but the more severe or 
complex the case, the more important therapist factors become.
(58)
More severe or chronic disorders also require more prolonged therapy.

677
Continuation and maintenance therapy
Some patients may beneﬁ  t from regular but less frequent ses-
sions of continuation or maintenance CBT or IPT to prevent relapse, with about eight additional sessions over the course of a year, to explore whether the techniques learnt in therapy are being used well and to identify potential triggers of relapse or recurrence. It is unrealistic to offer this to all those who receive an acute course of IPT or CBT, but it may be considered for those at high risk of relapse or recurrence due to residual symp-toms, history of highly recurrent episodes, ongoing severe psy-chosocial stressors, refusal to take continuation medications.A full course of CBT may also be offered now, rather thanduring the acute illness, if remission is partial with residual symptoms.
Treatment of bipolar disorder
Recent guidelines on treatment of bipolar disorder, providing supporting evidence, include those from the UK National Institute for Health and Clinical Excellence,

(59) the CANMAT consensus 
statement,(60) and the APA Practice Guideline.(61)
(a) Treating acute mania
Most mood stabilizers and antipsychotics have acute antimanic effects, but lithium or valproate are the drugs of ﬁ  rst choice. Since

Most mood stabilizers and antipsychotics have acute antimanic effects, but lithium or valproate are the drugs of ﬁ  rst choice. Since 
response may take 7 to 14 days, an antipsychotic is also often required, with effects within days in controlling the acute manic symptoms. The older antipsychotic, haloperidol should not be used with lithium due to risk of neurotoxicity syndrome. Benzodiazepines such as lorazepam and clonazepam may also be used temporarily to treat hyperactivity, insomnia, and agitation. The loss of insight, impaired judgement, hyperactivity, and disinhibited behaviour of manic patients often mean that hospitalization is required to ensure patient safety and commence treatment. For severe mania, ECT may occasionally be used.
(b) Treating bipolar depression

Treatment of bipolar depression is in principle similar to unipolar, but with mood stabilizer cover. If severity indicates antidepressant use, an SSRI, bupropion, or MAOI should be used, but not a tricyclic or SNRI, because of higher risk of mania and cycling. A mood stabi-lizer should be used in addition. Lamotrigine may produce beneﬁ  t 
alone. If cycling occurs in spite of this, an antipsychotic may be added, and the antidepressant cautiously reduced. ECT may be indi-cated, as in unipolar depression, and does not appear to lead to rapid cycling.
(c)  Continuation and maintenance treatment for 
Continuation treatment is needed after acute bipolar episodes,

Continuation treatment is needed after acute bipolar episodes, 
using the single medication or combination that has been used in acute treatment. Bipolar disorder is more recurrent than unipolar disorder, and mania can have catastrophic effects on personal life. The threshold for maintenance treatment is therefore lower and it should be used for 1 to 2 years following a ﬁ  rst episode of mania 
and longer after bipolar recurrences.
Choice of mood stabilizer includes an increasingly wide range. 
Probably lithium is still the ﬁ  rst choice, in the absence of major side 
effects. Doses should achieve blood levels 12 h after the last dose of 0.4 to 0.8 mmol/l, but sometimes higher levels are needed to prevent recurrences, and to reduce residual symptoms. After some

effects. Doses should achieve blood levels 12 h after the last dose of 0.4 to 0.8 mmol/l, but sometimes higher levels are needed to prevent recurrences, and to reduce residual symptoms. After some 
months blood levels are often very stable and only require occa-sional monitoring. Advice needs to be given on circumstances, which may disturb levels such as dehydration, gastrointestinal upset, travel, hot climates. Thyroid function should be monitored for hypothyroidism every 6 to 12 months.
Poor or partial responses are not uncommon, and valproate is a 
ﬁ rst choice alternative. Lamotrigine may be helpful where depres-
sion is a main feature. In treatment-resistant cases, two mood stabilizers may be required, particularly lithium and valproate. Antipsychotics, particularly olanzapine, may also be added or substituted if response is poor.
Antidepressants can often be withdrawn slowly after mood 
stabilizers are well established, but may be necessary to prevent

stabilizers are well established, but may be necessary to prevent 
chronic or recurrent depression. Antidepressants should not usu-ally be used alone for maintenance in view of the risk of mania. A few patients require multiple combinations of mood stabilizers, an antipsychotic, and an antidepressant.
Length of maintenance treatment varies, from a few years, to 
lifelong where several recurrences have followed withdrawal. Withdrawal of lithium should always be slow, over 3 to 6 months, to avoid rebound mania. It is best to do the same for the anticonvulsants.
(d) Rapid cycling
Treatment of established rapid cycling may be difﬁ  cult. It is impor-

tant to avoid a cycling alternation of antidepressant and antimanic medication, following too late after mood changes. The patient should be established on mood stabilizers, usually in high dose and often more than one in combination. Antipsychotic may be added. Antidepressants are better avoided but may be needed in addition, used cautiously and with slow dose increase and an effort to establish a constant dose. Thyroid function should be checked initially and regularly.
(e) Pregnancy
Management in pregnancy is complicated by the risk of foetal mal-formations with lithium and anticonvulsants. These should be withdrawn for the ﬁ  rst trimester. Antipsychotics and antidepres-

sants may be used if necessary. Olanzapine may be appropriate but safety of newer antipsychotics and antidepressants is less well established than for older ones. In later pregnancy lithium and anticonvulsant mood stabilizers may need to be reinstituted. Medication should be withdrawn at the time of delivery to avoid effects on the foetus, but started again as soon as possible thereafter, as risks of relapse are increased postpartum.
(a) Acute treatment of mania
Psychotherapy has not been evaluated in manic patients and the evidence for beneﬁ  t in bipolar disorders is for relapse reduction

Psychotherapy has not been evaluated in manic patients and the evidence for beneﬁ  t in bipolar disorders is for relapse reduction 
when delivered during euthymia. Access to therapy in most coun-tries is limited and it is important to use clinical management, supportive therapy, and psychoeducational sessions as part of gen-eral treatment. Use should be made of systematic care packages to address psychosocial problems, to facilitate recognition of early warning symptoms of relapse, and to implement self-monitoring and self-management strategies.
(59) Support should also include 
education about the disorder and treatment options, and help in 4.5.8 treatment of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 678
adjusting to the diagnosis and should, if possible, include the 
patient’s ‘signiﬁ  cant others’ . About six sessions of family therapy 
may have beneﬁ  cial effects extending beyond discharge.
Therapy with individuals with bipolar disorders can be challeng-
ing, requiring skilled and experienced therapists who also under-stand aetiology and pharmacology. There is a trend towards more 
cost-efﬁ  cient group approaches, which allow individuals to observe 
the strengths and weaknesses of coping strategies employed by peers. However, a key study of group psychoeducation found beneﬁ  ts only with a structured group with a coherent treatment 
plan and not with unstructured groups without expert professional leadership.
The therapies currently found effective to treat acute bipolar 
depressive episodes or to reduce the risk of future relapse in RCTs do not differ markedly in either their overall efﬁ  cacy or their core

depressive episodes or to reduce the risk of future relapse in RCTs do not differ markedly in either their overall efﬁ  cacy or their core 
content. They incorporate four key components: psychoeducation and adjustment to the disorder, lifestyle regularity and ‘harm reduction’ (reducing substance misuse), enhancing medication adherence, and developing self-management skills to reduce the risk of relapse by recognizing potential triggers or prodromal signs or symptoms.
There are no consistent predictors of therapy response. There 
is some consensus that patients with Axis I or II comorbidity, particularly substance misuse or borderline personality disorder will beneﬁ  t from an extended course of therapy. Likewise, where

is some consensus that patients with Axis I or II comorbidity, particularly substance misuse or borderline personality disorder will beneﬁ  t from an extended course of therapy. Likewise, where 
there have been many previous episodes of bipolar disorder, patients are unlikely to be able to assimilate and implement all the problem-solving and coping strategies being offered, in a time-limitedtherapy. Even where therapy does not clearly reduce relapse, many recipients value the opportunity to discuss their problems in detail, reporting improved quality of life and social functioning. Clinically, 
if the goal is relapse prevention, it may be appropriate to particu-
larly target for therapy those individuals at an earlier stage of their ‘bipolar career’ , whom evidence suggests may beneﬁ  t more.
(43)
Longer-term treatment of bipolar disorders
Supportive or other psychological therapies may extend over

(43)
Supportive or other psychological therapies may extend over 
considerable periods of time. People with affective disorders also form 15 to 20 per cent of the long-stay patient populations of United Kingdom and United States mental hospitals. Rehabilitation techniques, as applied to schizophrenia and other severe mental disorders, are important for instilling hope and developing day-to-day living skills in people with chronic or recurrent affective disorders. Lastly, individuals with chronic health problems are at high risk of non-adherence with medication. There is an important  role for psy-
chotherapy in enhancing the acceptance of long-term medication
(23,62)
and there is emerging evidence that psychological interventionstargeted directly or indirectly at enhancing medication adherence can have a beneﬁ  cial impact on outcome in bipolar disorders.

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58. Roth, T. and Fonagy, P . (1996). What works for whom?  pp. 57–103. 
Guilford Press, London.
59. NICE. (2006). Bipolar disorder. The management of bipolar disorder 
in adult: children and adolescents, in primary and secondary care .
NICE Clinical Guideline 38 National Institute for Health and Clinical Excellence, London.4.5.8 treatment of mood disorders

SECTION 4  clinical syndromes of adult psychiatry 680
60. Y atham, L.N., Kennedy, S.H., O’Donovan, C., et al. (2005). Canadian 
network for mood and anxiety treatments. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder: consensus and controversies. Bipolar Disorders ,7(Suppl. 3), 5–69.
61. American Psychiatric Association. (2002). Practice guideline for the 
treatment of patients with bipolar disorder  (2nd edn). American 
Psychiatric Press, Washington.
62. Tacchi, M.J. and Scott, 
J.(2005). Medication adherence in schizophrenia 
and bipolar disorders , p. 110. John Wiley & Sons, London.
4.5.9 Dysthymia, cyclothymia, 
and hyperthymia
Subthreshold affective conditions, 
personality, and temperament
Long before psychiatry moved to the outpatient arena in the latter

Long before psychiatry moved to the outpatient arena in the latter 
part of the twentieth century, psychiatrists had observed milder mood disturbances among the kin of patients hospitalized for endogenous or psychotic depressions or mania. Some were described as sullen, morose, or otherwise moody, without discrete episodes; others reported self-limited episodes, but often went untreated. With the advent of modern treatments, practitioners are being increasingly consulted by patients presenting with atten-uated affective disturbances. Although the relationship of these ambulatory mood states and more classical severe affective disorders has not been resolved, the re is emerging sleep electroen-
cephalography ( EEG ) and familial-genetic evidence
(1–3) that a

(1–3) that a 
continuum exists between them. Along the same lines, studies con-ducted in the United States and Germany
(4,5) into what were once 
described as ‘neurotic’ depressions have revealed a progression to more endogenous, psychotic, or bipolar switching. For these and related reasons, current ofﬁ  cial classiﬁ  cation systems such as the 
ICD-10 and DSM-IV , have dropped the neurotic-endogenous dichotomy. Sceptics would perhaps argue that the new categoriza-tion of depressive disorders into dysthymic and major subtypes is not much of an improvement. Nonetheless, the new terminology has drawn attention to a large universe of human suffering that had been neglected in the past, and the conceptualization of dysthymia as a variant of mood disorder has had a far-reaching impact  on diagnos-tic and therapeutic habits of clinicians worldwide.
(6) The emerging 
concept of the bipolar spectr um, which does include manic, cyclic

concept of the bipolar spectr um, which does include manic, cyclic 
depressive (bipolar II), cyclothymic, hyperthymic  and relatedconditions, is beginning to have a similar impact on practice.
(7)
The subthreshold mood disorders are not only in continuum 
with more pathological mood states, but they also provide a bridge with normal affective conditions. In this context, temperament, as a construct encompassing affective personalities, is currently enjoying a renaissance as one of the possible substrates for the origin of mood disorders. T emperament classically refers to an adaptive mixture of traits which, in the extreme, can lead toillness or modify the expression of superimposed affective states. The subthreshold conditions covered in this chapter represent
the extreme expressions of these temperaments. A new self-administered instrument, the TEMPS-A,
(8) now validated in 10

(8) now validated in 10 
language versions, is being used internationally to measure the classical constructs of depressive, cyclothymic, hyperthymic, and irritable, as well as anxious temperaments.
In the current literature, various terms such as ‘minor affective 
states’ , ‘intermittent depression’ , ‘hysteroid dysphoria’ , and ‘atypical depression’ are often used for subthreshold disorders.
(9) These 
terms are avoided here, because in contemporary practice these conditions are at least as ‘typical’ as major mood disorders: their impact on the sufferer is not time-limited, nor minor, and involves more than a state of demoralization and moral foible. The follow-ing passage from Sir Aubrey Lewis
(10) is à propos :
. . . Severe emotional upsets ordinarily tend to subside, but mild emo-

tional states . . . tend to persist, as it were, autonomously. Hence the paradox that a gross blatant psychosis may do less damage in the long run than some meager neurotic incubus: a dramatic attack of mania or melancholia, with delusions, wasting, hallucinations, wild excite-ment may have far less effect on the course of man’s life than some deceptively mild affective illness which goes on so long that it becomes inveterate. The former comes as a catastrophe and when it has passed the patient takes up his life again . . . while with the latter he may never get rid of his burden.
It is a curious fact that most subthreshold affective conditions,

It is a curious fact that most subthreshold affective conditions, 
while symptomatologically attenuated, tend to pursue a chronic course. This raises the question, partially addressed in this chapter, whether these conditions in their trait expressions might serve some useful function, even as they burden the individual with cares and instability which could predispose to full-blown affective disease. By their very chronicity, these subaffective conditions pose difﬁ  cult 
conceptual and clinical questions about their differentiation from personality disorders.
(11) Sceptics might argue that subthreshold 
affective conditions are nothing more than personality disorders and/or expressions of ‘neuroticism’ . Actually, a close examination of the Eysenck personality inventory, which ranges over a large terrain of depressiveness, anxiousness, emotionality, and mood lability among others, reveals low-grade intermittent affective symptomatology.

(12) And at least one genetic investigation has 
reported that neuroticism and major depression in women share substantial genetic underpinnings.
(13) Nonetheless, clinicians have 
always preferred categorical constructs, because neuroticism and related personality constructs do not do justice to the rich clinical phenomenology of disorders within the subaffective realm. I ﬁ  nally 
wish to point out that terms like ‘neurotic’ , ‘psychopathic’ , or ‘personality disorder’ used as epithets to describe a person have pejorative connotations. They tend to describe what is negative about someone, whereas ‘temperament’ refers to the optimum mixture of both liabilities and assets regarding a human being, thereby rendering therapeutic work possible with relatively little countertransference. This is particularly relevant when we consider the distinct possibility that the many dysthymic and cyclothymic individuals might otherwise be labeled ‘borderline.’
(11)
The dysthymic spectrum
History

(11)
History
The term ‘dysthymia’ (meaning ‘bad mood’) originated in classical Greek and is still in current use in that country with the same con notation.

681
In the Hippocratic School, it was considered as part of the broader 
concept of melancholia (meaning ‘black bile’). A temperament pre-disposed to melancholia was also delineated, and referred to indi-viduals who were lethargic, brooding, and insecure. It was not until the early nineteenth century that dysthymia was reintroduced into medicine by the German physicians, Stark and Fleming to describe depressions in inpatients that pursued a chronic course.
(14)
Eventually, dysthymia came to subsume all mood disorders. The major residue of dysthymia in the latter sense in Europe todayis the French rubric of les dysthymies , as a synonym for troubles
de l’humeur ; the DSM-IV or ICD-10 ‘dysth ymic disorder’ in that 
country is translated as le trouble dysthymique .
The more direct lineage of our current usage of the term dysthy-

mia is to be found in the latter part of the nineteenth century in the work of Kraepelin, who delineated the depressive disposition as one of the constitutional foundations of affective episodes. The condition often began early in life, such that by adolescence many showed an increased sensitivity to life’s sorrows and disappoint-ments: they were tormented by guilt, had little conﬁ  dence in their 
abilities, and suffered from low energy. As they grew into adult-
hood, they experienced ‘life with its activity [as] a burden which

hood, they experienced ‘life with its activity [as] a burden which 
they habitually [bore] with dutiful self-denial without being compensated by the pleasures of existence’ . In some, these tempera-mental peculiarities were so marked that they could be considered ‘morbid without the appearance of more severe, delimited attacks . . .’ (clearly foreshadowing the modern concept of trait dysthymia). In other cases, recurrent melancholia arose from this substrate without definite boundaries (again anticipating the concept of ‘double-depression’).
Subsequently, Kurt Schneider in his opus Psychopathic 
Personalities  devoted considerable space to a depressive type whose 
entire existence was entrenched in suffering. Building on this rich phenomenological tradition, our research in Memphis
(15) helped

(15) helped 
in operationalizing the core characteristics of such patients encoun-tered in contemporary practice: gloomy, sombre, and incapable of having fun; brooding, self-critical, and guilt-prone; lack of con-ﬁ dence, low self-esteem, preoccupation with failure; pessimistic, 
easily discouraged; easy to tire, sluggish, and bound to routine; non-assertive, self-denying, and devoted; shy and sensitive. These traits have excellent internal consistency and discriminatory ability.
(16) Similar concepts have also appeared in the Japanese 
literature,(17) with particular emphasis on self-critical attitudes, 
persistence in work habits, and devotion to others. Finally, the French construct of la depression constitutionelle
(18) has empha-
sized the lethargic aspects with a sense of inadequacy. A self-rated scale in all of these languages

(8) now can assist in reliable and valid 
assessment of depressive temperament traits.
The classical tenet in psychiatry has been that affectively ill 
patients recover from their acute episodes with relatively little symptomatic residua and dysfunction. Community psychiatry, which has given renewed visibility to the temperamentally expressed low-grade ﬂ  uctuating depressive disorders, has challenged this 
classic view. With the advent of DSM-III, such patients are now ofﬁ cially designated as ‘dysthymic.’ In the ICD-10 classiﬁ  cation,

classic view. With the advent of DSM-III, such patients are now ofﬁ cially designated as ‘dysthymic.’ In the ICD-10 classiﬁ  cation, 
the low-grade depressive baseline is considered the main pathology; only an occasional superimposed depressive episode is permitted, provided that it is mild. In DSM-IV , at least two patterns have been described: pure dysthymia uncomplicated by major depression and a more prevalent pattern of dysthymia complicated by major depressive episodes that could be even moderate or severe in inten-
sity (and which has been dubbed ‘double depression’).
The mystery of this incapacitating depressive subtype—long 
recognized, but only recently sanctioned in ofﬁ  cial diagnostic 
manuals—is that, in their habitual condition, sufferers lack the classical ‘objective’ or ‘major’ signs of acute clinical depression, such as profound changes in psychomotor and vegetative functions. Instead, patients consult their doctors for more ﬂ  uctuating com-

plaints consisting of gloominess, lethargy, self-doubt, and lack of joie de vivre ; they typically work hard, but do not enjoy their work; 
if married, they are deadlocked in bitter and unhappy marriages which lead neither to reconciliation nor separation; for them, their entire existence is a burden: they are satisﬁ  ed with nothing, 
complain of everything, and brood about the uselessness of existence. As a result, in the past those who could afford it were condemned to the couch for what often proved to be interminable analysis. The legitimization of dysthymia as a clinically signiﬁ  cant 
variant of affective disorder in both the United States and WHO classiﬁ  cations has helped the cause of more cost-effective 
treatments.
T o sum up, for nearly 2500 years physicians have described 
individuals with a low-grade chronic depressive proﬁ  le marked

individuals with a low-grade chronic depressive proﬁ  le marked 
by gloominess, pessimism, low enjoyment of life, relatively low drive, yet endowed with self-critical attitudes and suffering for others.
(19)This constellation is as much a virtue as it is a disposition 
to melancholy, and many dysthymic patients presenting clinically have various admixtures of major depression. This is compatible with a spectrum-concept of depressive illness, which deﬁ  nes various 
degrees of severity.
Clinical picture and diagnostic considerations(20)*

Diagnostic criteria for dysthymia in both DSM-IV and ICD-10 stipulate a two-year duration of low-grade depressive symptoms, exclusive of such indicators of severity as suicidality and psycho-motor disturbances. Dysthymia is distinguished from chronic major depressive disorder by the fact that it is not a sequel to well-deﬁ ned major depressive episodes. Instead, patients often complain 
that they have always been depressed. Most are of early onset (less than 20 years). A late-onset subtype ﬁ  rst manifesting after the age 
of 50 is much less prevalent and has not been well characterized clinically, but it has been identiﬁ  ed largely through studies in the 
At their best, dysthymic individuals invest whatever energy they 
have in work, leaving none for leisure or social activities. According to T ellenbach, such dedication to work represents overcompensa-

tion against depressive disorganization. Kretschmer had earlier 
suggested that such persons were the ‘backbone of society,’ devot-ing their lives to jobs that require dependability and great attention to detail. These features represent the obsessoid facet of dysthymia. Such individuals may seek outpatient counseling and psychotherapy for what some clinicians might consider ‘existential depression’: individuals who complain that their life lacks lustre, joy, and mean-ing. Others present clinically because of an intensiﬁ  cation of their 
gloom to the level of clinical depression; history of lifelong low-
∗ Unless otherwise speciﬁ  ed, in the remainder of this chapter, references to 
concepts, historical developments, and research covering dysthymia and cyclothymia through the year 2000 can be found in this centenary review of Kraepelinian psychiatry.

(20)4.5.9 dysthymia, cyclothymia, and hyperthymia

SECTION 4  clinical syndromes of adult psychiatry 682
grade depressive symptoms would distinguish them from episodic 
major depressive patients.
The proverbial dysthymic patient will often complain of having 
been ‘depressed since birth’ . In the eloquent words of Kurt Schneider, “they view themselves as belonging to an ‘aristocracy of suffering” . These hyperbolic descriptions of suffering in the absence of more objective signs of depression earn such patients the label of ‘characterological depression’ . The description is further reinforced by the ﬂ  uctuating depressive picture that merges imperceptibly 
with the patient’s habitual self, leading to the customary clinical uncertainty as to whether dysthymic disorder belongs to the affec-tive or personality disorder domains.
At their worst, patients with low-grade depression having an

At their worst, patients with low-grade depression having an 
intermittent course can present such instability in their life, includingsuicidal crises, that some clinicians would entertain the diagnosis of borderline personality disorder. This is not consistent with the classic picture of dysthymia arising from a temperamental type with more mature ego structure described above. Depressives with unstable (that is to say, ‘borderline’) personality structure more often belong to the irritable cyclothymic–bipolar II spectrum.
The greatest overlap of dysthymia is with major depressive 
disorder, but differs from it in that symptoms tend to outnumber 
signs (more subjective than objective depression). Thus, marked

signs (more subjective than objective depression). Thus, marked 
disturbances in appetite and libido are uncharacteristic, and psy-chomotor agitation or retardation is not observed. Nonetheless, subtle ‘endogenous’ features are not uncommonly reported: iner-tia, lethargy, and anhedonia that are characteristically worse in the morning. Because many patients with dysthymia presenting clini-cally ﬂ  uctuate in and out of a major depression, the core DSM-IV 
criteria for dysthymia tend to emphasize vegetative dysfunction, whereas the alternative criterion B for dysthymia in a DSM-IV appendix lists cognitive symptoms; although the latter appear more characteristic of trait dysthymia, the DSM-IV ﬁ  eld trial could not 
demonstrate their speciﬁ  city for dysthymia.
A Milan-San Diego collaboration of a large sample from com-

munity and primary-care medical settings revealed that negative mood (by deﬁ  nition), along with low energy, poor concentration, 
low self-esteem, sleep and appetite disturbance, and hopelessness (in descending order) were the most common symptoms of dysthymia. These data suggest that the cognitive and somatic symp-toms are not easily separable in practice. None the less, this study did raise the possibility that factors could be discerned along two different axes: ‘negative affectivity’ and ‘lassitude with poor con-centration’ . In our experience, patients loading on the latter factor often complain of hypersomnia and may exhibit subtle bipolar signs; alternatively, they might have some link to the poorly deﬁ  ned 
constructs of neurasthenia, chronic fatigue syndrome, and ﬁ  bro-

myalgia. In terms of differential diagnosis, patients with chronic fatigue syndrome present with disabling fatigue and, typically, deny 
depressive symptoms; patients with ﬁ  bromyalgia complain of pain; 
by contrast, the typical patient with dysthymia cannot stop relating to the physician his or her litany of depressive symptoms. Polysomnography, though not yet deﬁ  nitive, may shed some light 
on differentiating ﬁ  bromyalgia from dysthymia proper.
Although dysthymic disorder represents a more restricted concept

Although dysthymic disorder represents a more restricted concept 
than does its parent, neurotic depression, it is still quite heteroge-neous. Anxiety is not a necessary part of its clinical picture, yet dysthymia is sometimes diagnosed in patients with anxiety and neurotic disorders. That clinical situation is perhaps to be regarded as a secondary or ‘anxious dysthymia’ or, as some British authors seem to prefer, as part of a ‘general neurotic syndrome’ (an implicit partial return to the now defunct concept of neurotic depression).
The clinical picture of dysthymic disorder that emerges from the 
foregoing descriptions is quite varied, with many who ﬂ  uctuate in

foregoing descriptions is quite varied, with many who ﬂ  uctuate in 
and out of major depression, whereas in others the pathology is woven into the habitual self. Prospective follow-up supports a con-tinuum between temperament, dysthymia and major depression. These considerations suggest that a clinically satisfactory opera-tionalization of dysthymia must include both symptoms and trait characteristics (Table 4.5.9.1). The following vignette illustrates this more prototypical form of dysthymic suffering.
Case Study : This 37-year-old never-married male teacher

presented with the complaint that he was ‘tired of living’ and was considering ‘ending it all’ . He said that much of his life had been ‘wasted’ , he had never known any joy, and that all human existence for him was a ‘tragic mistake of God’ . He was known to be a dedi-cated and talented teacher, but he felt all his efforts had been ‘use-less and in vain’ . He said he probably was ‘born depressed’ , because he had not known any happiness and that the only utility he could have for mankind was ‘to serve as a specimen to be researched—to shed light on human misery’ . Although he conceded that some women found him interesting, even intellectually stimulating, he said he could not enjoy physical intimacy, that even orgasm lacked passion; nonetheless, he masturbated frequently, fantasizing about married female teachers—only to feel guilty. We could not docu-ment any major affective episodes. He stated that he had always functioned at a ‘mediocre level’ (which was at variance with the

good feedback students had given him year after year); but did 
admit he ‘appreciated work, because there was nothing else to do’ . He denied alcohol and drug habits. There had never been any periods of hypomania, but one of his maternal aunts had been treated for a ‘cyclical depression’ and was apparently doing well on lithium. The patient’s mother was a sombre serious work-oriented woman who had raised three children and had done voluntary work for the church, but had no depressive complaints. His father had died from a coronary attack, but his side of the family was otherwise unremarkable.
Although both DSM-IV and ICD-10 omit suicidal preoccupa-
tions in their diagnostic criteria for dysthymia, as testiﬁ  ed by the 
above case, this is what often brings patients to clinical attention.
Course(20)

An insidious onset of depression dating back to late childhood or the teens, preceding any superimposed major depressive episodes by years, even decades, is the most typical developmentalTable 4.5.9.1  The core characteristics of dysthymia
Long-standing subthreshold depression of a ﬂ  uctuating or persistent nature
Gloomy and joyless disposition
Brooding about the past and guilt prone
Low drive and lethargyLow self-esteem and preoccupation with failureIdentiﬁ  es suffering as part of the habitual self
Summarized from Akiskal.(19)

683
background of dysthymic disorder. A return to the low-grade 
depres sive pattern is the rule following recovery from superim-
posed major depressive episodes, if any, hence the designation 
‘double depression’ .
Few studies have studied the phenomenology of dysthymia in 
childhood. DSM-IV does not seem to distinguish between child-
hood and adult dysthymia, yet current clinical experience indicates 
that the main symptoms in childhood dysthymia include irritabil-
ity, low self esteem, fatigue, low mood, guilt, poor concentration, 
anhedonia, and hopelessness; as in adults, comorbid anxiety disor-
ders were prevalent; suicidality was more common in adolescents. 
These ﬁ  ndings should be useful in dysthymic children in future 
studies. A long-term prospective Pittsburgh study of prepubertal 
children has revealed an episodic course of dysthymia with remis-
sions and exacerbations, and eventual complication by major

sions and exacerbations, and eventual complication by major 
depressive episodes, as well as hypomanic, manic, or mixed episodes 
postpubertally. Persons with dysthymic disorder presenting clini-
cally as adults tend to pursue a chronic ‘unipolar’ course, which 
may or may not be complicated by major depression: they rarely 
develop spontaneous hypomania or mania. However, when treated 
with antidepressants, some adult patients with dysthymia may 
experience brief hypomanic switches that typically disappear 
when the antidepressant dose is decreased. Although ICD-10 and 
DSM-IV would not ‘allow’ the occurrence of such switches in 
dysthymia, systematic clinical observation have veriﬁ  ed their occur-
rence in between 10 and 30 per cent of dysthymic patients. In that 
special dysthymic subgroup, the family histories are typically

special dysthymic subgroup, the family histories are typically 
positive for bipolar disorder. Such patients, often conforming to 
the double depressive pattern, represent a clinical bridge between 
major depressive disorder and bipolar II.
A 12-year NIMH prospective study has shown that patients 
with major depressive disorder spent 44 per cent of their course in 
low-grade depression (versus 15 per cent of time in major depres-
sive episodes). This suggests that major depression, dysthymia, or 
otherwise subsyndromal depression constitute somewhat artiﬁ  cial 
conventions on the threshold and duration of depressive illness, 
representing alternative manifestations of the same diathesis. In 
this context, residual intermorbid depressive symptoms have been 
conﬁ  rmed as being strongly predictive of a rapid relapse into a new 
major depressive episode. Various ‘major’ and ‘minor’ depressive

major depressive episode. Various ‘major’ and ‘minor’ depressive 
conditions described in DSM-IV and its appendix must not be 
viewed as distinct depressive subtypes, but part of a symptomatic continuum. Fig. 4.5.9.1 shows a diagram of these putative relation-
ships within a broad depressive spectrum.
Epidemiology(20)
From 1966 to 1980, Index Medicus  listed no more than 10 articles 
on chronic depressions. Since 1980, when dysthymia was ﬁ  rst intro-
duced in DSM-III, at least 500 articles have appeared on chronic 
depression, mostly on dysthymia. This phenomenal growth in 
research interest parallels the increasing public health signiﬁ  cance 
of this disorder. It is estimated that 3–5 per cent of the world
population is suffering from dysthymia. Like major depressive dis-
orders, dysthymia is twice as common in women as in men. Because 
of its chronicity, dysthymia is among the most prevalent psychiat-

ric conditions in clinical practice. Dysthymia is more disabling, as 
far as quality of life in social and personal areas, work, and leisure, 
than depression in the setting of a severe anxiety disorder like 
agoraphobia. Celibacy is also common in early-onset dysthymia, 
but not for long; modern successful treatments often lead to 
a change in marital status!
UCLA research in primary care has focused on depressive 
symptoms falling short of the major depressive threshold, as far as 
symptom intensity is concerned, as well as falling short of the 
two year duration criterion for dysthymia. Despite its chronicity, 
50 per cent of people remain unrecognized by general practitio-
ners. Despite the low-grade nature of their depressive complaints,

ners. Despite the low-grade nature of their depressive complaints, 
these patients report high degrees of morbidity and impairment in 
a variety of health domains and quality of life, including ‘bed days’ 
(namely, the number of days per year they stayed ill in bed). Actually, 
these impairments are generally more pronounced than those of 
patients with a variety of medical conditions, such as hypertension, 
diabetes, arthritis, and chronic lung disease; only coronary artery 
disease exceeded the disability of low-grade depression in several 
domains. Stroke has recently been added on this list.
In light of the foregoing developments, both the World Psychiatric 
Association(21) and the World Health Organization(22) have devel-
oped programmes to address the challenges of educating general

oped programmes to address the challenges of educating general 
practitioners in the proper recognition and treatment of dysthymia.
Aetiological considerations(20)
Some sensitivity to suffering, a cardinal feature of the depressive 
temperament, represents an important attribute in a species like 
ours, where caring for young and sick individuals is necessary for 
survival. This temperament, historically the Anlage  of dysthymia, 
in the extreme often leads to clinical depression. The constitutional 
viewpoint, while dominant in the early part of the twentieth cen-
tury, gradually disappeared from psychiatric thinking. One reason 
was that Kurt Schneider preferred to conceptualize such conditions 
as ‘psychopathy’ , by which he meant abnormal personality develop-
ment. Independently, Freud’s disciples took this one step further

ment. Independently, Freud’s disciples took this one step further 
and, eventually in outpatients, all milder depressions with a ten-
dency to chronicity came to be considered as the expressions of 
a character neurosis. In support for this position, these authors 
could point to the long-standing nature of the interpersonal difﬁ  -
culties in the lives of these individuals. When, and if, antidepres-
sants were prescribed, they were given in homeopathic doses; worse, 
many patients received stimulants or benzodiazepines rather than 
genuine antidepressants. Failure to respond to these incorrectly 
chosen pharmaceutical agents seemed to further reinforce the 
notion of a ‘character’ defect.Fig. 4.5.9.1 Diagram to show putative relationships within a broad depressive 
spectrum.
4.5.9 dysthymia, cyclothymia, and hyperthymia

SECTION 4  clinical syndromes of adult psychiatry 684
Several lines of observation during the latter part of the 20th 
century have challenged the concept of ‘character neurosis’ as an explanation for low-grade depression, and thereby forced a return to the more classical European concept of temperament with its biological underpinnings. First, in a 1980 Memphis study of rapid eye movement (REM) latency (normally 90 min, measured from sleep onset to the ﬁ  rst REM period) conducted in ‘depressive char-
acters’ who were not in a state of major depression, we reported that REM latency was less than 60 min, and REM was redistributed to the early part of the night (which was the reverse of what we observed in chronic anxious patients). Moreover, a family history for major affective illness (including bipolar) was signiﬁ  cantly high 
in short-REM latency patients. (The reverse was true for those with familial alcoholism and sociopathy.) The sleep ﬁ  ndings were so

in short-REM latency patients. (The reverse was true for those with familial alcoholism and sociopathy.) The sleep ﬁ  ndings were so 
reminiscent of those seen in major affective illness that we were compelled to give our patients systematic open trials with desipramine and nortriptyline (the best-tolerated secondary amine tricyclics in those days) or lithium carbonate if antidepressants failed (based on the observation of familial bipolar disorder in some). Nearly 40 per cent remitted, of whom one out of three developed brief hypomania. The sleep ﬁ  ndings have been replicat-
ed in other laboratories. Furthermore, a Hungarian study has 
shown that patients with dysthymia experience transient lifting of

shown that patients with dysthymia experience transient lifting of 
their mood with sleep deprivation. Other studies have shown high rates of affective illness in a systematic familial investigation of dysthymic probands. There also exist dysthymic patients whose lifelong suffering and discontent appear, in retrospect, a legacy of an unsatisfactory childhood marked by deprivation or abuse at the hands of alcoholic and/or sociopathic parents or step-parents. Although it is clinically attractive to invoke the notion of ‘learned helplessness’ secondary to such inescapable childhood traumata, an alternative hypothesis is that the helplessness of these individu-als might develop secondary to an inherited diathesis which biases these children’s early experiences in a dysphoric direction.
As for neuroendocrine markers, thyroid-releasing hormone-

thyroid-stimulating hormone challenge and electrodermal activity similar to those with major depressive disorders are the main ﬁ  nd-
ings; by contrast, dexamethasone suppression and catecholamine metabolism are essentially unaltered in dysthymia. These observa-tions, along with the REM latency ﬁ  ndings, suggest that dysthymia 
represents trait depression. Coupled with the family history data, this traitness can be postulated to be of constitutional origin. Certainly, the occurrence of major affective episodes in the long-term course of dysthymia, in both community and clinical samples, is in line with this position. It is, therefore, of great theoretical and practical signiﬁ  cance that shortened REM latency has been report-
ed in the offspring of the affectively ill. More recently a variety of other biological ﬁ  ndings have been reported in dysthymia, further

ed in the offspring of the affectively ill. More recently a variety of other biological ﬁ  ndings have been reported in dysthymia, further 
strengthening the link with major depression: low testosterone and 
adrenal-gonadal steroid levels,
(24) neuro-immune abnormali-
ties,(25) effects of prenatal maternal dysthymia on foetal growth,(26)
as well as small genual corpus callosum volume(27) and enlarged 
amygdalar volume.(28) Coupled with s-allele polymorphism of 
the serotonin transmitter,(29,30)  that subthreshold depression, 
however deﬁ  ned, is not a ‘neurotic’ phenomenon in the traditional 
psychodynamic sense of the term, but part of the spectrum of depressive illness! Table 4.5.9.2 summarizes the foregoing links between dysthymia and major depressive disorder, and which sup-port its inclusion within the family of mood disorders.There are also exist medical and neurological factors that may 
contribute to dysthymic symptom formation. Actually, joint medi cal-

neurological and non-affective psychiatric disease is often contrib-utory to extreme refractoriness among the chronic depressive states of these patients. Such patients are at risk for suicide, especially those with epilepsy or progressive degenerative neurological disease. Interestingly, living with a medically disabled spouse or family member, too, can be associated with some chronicity of depression.
The emergence of pathogenetic understanding, as outlined above, 
is all the more impressive, given the controversies on the very nature of dysthymia and its legitimacy as a nosological entity.
(31)
Treatment(20)

(31)
The trait nature of dysthymia can be further observed in the fact that dysthymia often pursues an unrelenting course towards chro-nicity. Thus, spontaneous recovery has been shown to occur in no more than 13 per cent of subjects in the community over 1 year. In outpatient clinics, the outcome is somewhat better, but this is prob-ably due to the treatment received and a longer follow-up.
Most classes of antidepressants have been shown to be effective 
in dysthymia in double-blind studies (Table 4.5.9.3). The rationale for using classic antidepressants such as tricyclic compounds in our mood clinic was our observation of shortened REM latency in Table 4.5.9.2  Evidence for considering dysthymia as a variant of 
major depressive disorder
Familial affective loading
Phase advance of rapid eye-movement sleep

Diurnality of inertia, gloominess, and anhedonia
Thyroid-releasing hormone-thyroid-stimulating hormone challenge test 
 abnormalities
Low testosterone
Lowered interlukin-1-beta production
Amydalar enlargement
s-allele in serotonin transporter gene
Prospective course complicated by recurrent major depressive episodesPositive response to selected thymolepticsTreatment-emergent hypomania
Updated from Akiskal.(19)
Table 4.5.9.3 Major controlled pharmacological trials in dysthymia 
worldwide*
Reference Country Medication
Vallejo et al. (1987) Spain Phenelzine versus imipramine
Kocsis et al. (1987) USA Imipramine versus placebo
Stewart et al. (1989) USA Phenelzine versus placebo
Thase et al. (1996) USA Sertraline versus imipramine
Vanelle et al. (1998) France Fluoxetine versus placebo
Lecrubier et al. (1996) France Amisulpride versus placebo

Versiani et al. (1997) Brazil Moclobemide versus imipramine
*Summarized from references(19,20)

685
dysthymic subjects in our sleep laboratory. Irreversible monoamine 
oxidase inhibitors such as phenalzine were used because of the belief that non-classical depressions respond preferentially to this class of drugs; the same can be said for the reversible inhibitors of type A monoamine oxidase. Amisulpride was tried, because it reverses ‘negative’ symptoms in schizophrenia and, by analogy, it was hypothesized that the low motivation and lethargy seen in some patients with dysthymia reﬂ  ected a shared underlying dimen-

sional transnosological pathology. The selective serotonin re-uptake inhibitors (SSRIs) were used empirically, because of good tolerance compared with the tricyclic antidepressants, and later it was suggest-ed that improvement in dysthymia correlates with normalization of serotonergic indices. The foregoing trials, conducted in different countries during the past 12 years represent the most eloquentevidence for the increasing worldwide acceptance of the concept of dysthymia as a clinically signiﬁ  cant variant of affective disorder.
(21,22)
The treatment of dysthymia should continue in most cases for 
2 years or more. Tricyclic antidepressants have too many side-effects in clinically effective doses (desipramine equivalent of 150 mg or more per day). Given dietary and medication prohibitions, mono-amine oxidase inhibitors are also not practical as ﬁ  rst-line drugs.

Overall good tolerance in long-term use, despite sexual side-effects, has made the SSRIs ﬁ  rst-line intervention treatment for dysthymia; 
given that many people with dysthymia are young individuals who should be eager to form families, their acceptance of long-term SSRI use is an indication that the alleviation of the depressive suf-fering of dysthymia is genuine and far outweighs the sexual dys-function. However, 75 to 150 mg bupropion-SR can be taken in the morning on the desired day of sexual union, but preferably no more than once a week. Moclobemide also spares sexual function, 
but seems more effective in anxious and milder cases of dysthymia. 
Amisulpride, which rarely causes amenorrhoea and/or galactor-rhoea, is otherwise well tolerated in dysthymia in the more lethar-gic forms of the illness seen in general medical practice.
The dosage of nearly all antidepressants in dysthymia is in the full

The dosage of nearly all antidepressants in dysthymia is in the full 
range for that recommended for major depression (20–40 mg for ﬂ uoxetine). In the case of amisulpride, the dosage is low (25–50 mg), 
because at this dosage the drug is a dopamine agonist, believed to be the necessary ingredient for its mechanism of action in dysthymia. Both dysthymia and double depression respond equally well, and the duration of underlying dysthymia does not seem to matter. The main difference in treatment for these two course patterns is that dysthymia need not be treated for a lifetime, but double depression should probably be treated indeﬁ  nitely. Women seem to have a 
preferentially better response to SSRIs, which have the added benefit of treating the premenstrual accentuation of dysthymic symptoms. Borderline thyroid function (e.g. a high baseline thyroid-stimulating hormone level) preferentially occurs in women with dysthymia, so that these women would beneﬁ  t from thyroid

augmentation (levothyroxine 175 mg/day) of the antidepressant. In those patients who oversleep in the morning, terminal sleep deprivation and/or morning phototherapy represent useful adjuncts to antidepressants. Although there are no controlled studies in children, our clinical experience indicates that SSRIs often prove effective in this population, with the appropriate dos-age reduction for body-weight. In adults, concurrent personality disturbances (for instance, obsessoid, avoidant, dependent, and hostile features) do not compromise therapeutic responses. Indeed, more often than not, such personality disturbances recede with the successful alleviation of dysthymic suffering; social function

improves in tandem. (However, extremely hostile patients, who may meet symptomatological criteria for ‘dysthymia’ but whose irritable dysphoria more appropriately belongs to the cyclothymic domain, are best managed with mood-stabilizing anticonvulsants, for example divalproex 600 to 1200 mg/day.)
In a Memphis study, we have shown that, with the judicious use 
of the foregoing modalities in private practice, three out of four patients with dysthymia engulfed in gloom for much of their lives had sustained remissions for five or more years. Depressive episodes and suicidal preoccupation and/or crises were prevented,

in tandem with the alleviation of the dysthymia. Approximately 15 per cent experienced ‘overcorrection’ of their dysthymia in the direction of mild hypomania; this is particularly likely in the presence of inhibited-social phobic traits as part of dysthymia, and when the family history is bipolar. The hypomania is typically short-lived, and tends to disappear when the antidepressant dose is reduced; in some cases, it is necessary to provide lithium (600–900 mg/day) or valproate augmentation (500–750 mg/day). The question has been raised whether selective serotonin-reuptake inhibitors, in particular fluoxetine, change the personality in a hyperthymic direction. In our experience, most observed changes are compatible with adaptive behaviour that emerge as a result of alleviation of depressive suffering; the more distinctly protracted hypomanic changes nearly always require familial bipolar diathesis. It is, nonetheless, true that with SSRIs we have entered an era of ‘dimensional

suffering; the more distinctly protracted hypomanic changes nearly always require familial bipolar diathesis. It is, nonetheless, true that with SSRIs we have entered an era of ‘dimensional psychopharmacology’ , whereby the clinician could dose the patient to a desired end from a functional standpoint. Many become care-less rather than careless. The present author has also encountered some patients treated with SSRIs who view a life without cares as negative; in such cases, one should opt for very low doses and a more gradual lifting of the dysthymia, and help the patient adjust to a new self-image of normalcy.

As for psychotherapy, there is little credible evidence for its 
efﬁ cacy as monotherapy in the treatment of dysthymia. Actually, 
some female mental health experts have argued that exploration of one’s mental inadequacies, in the ‘passive’ psychoanalytical situation, is particularly negative for women; the more ‘active’ cognitive behavioural approaches, which encourage thinking, and behaviours reinforcing for the individual, are preferable. Many clinicians proﬁ  tably use the latter strategy along with phar-
macotherapy to boost the self-esteem of the patient. In a more practical vein, there are clinical management strategies that are spe-ciﬁ cally useful for both the patients and their clinicians (Table 4.5.9.4). 
Table 4.5.9.4  Psychotherapeutic principles in dysthymia*
Provide a believable dose of optimism
Optimize compliance to pharmacotherapy
Limit destructive expression of negative feelings
Address accumulated conﬂ  icts
Combat postdepressive resignation and inertia

Provide support for patient and signiﬁ  cant others
Be aware of countertransference feelingsConsult experts with extensive experience in treating chronic depressionGradually mobilize patient’s skills and resources
*Updated from Akiskal.(6)4.5.9 dysthymia, cyclothymia, and hyperthymia

SECTION 4  clinical syndromes of adult psychiatry 686
It is particularly important for the clinician not to be submerged
by the negative thinking of the patient, and it is even more crucial for the therapist to recognize that a relative lack of progress can generate feelings of ‘impotence’ and countertransference; periodic consultation with more experienced clinicians in the treatment of chronic depression would be desirable.
Interpersonal psychotherapy has been used in medication

Interpersonal psychotherapy has been used in medication 
failures. This is best viewed as a more practical abbreviation of psychodynamic psychotherapy, with a strong emphasis on support and encouragement for patients with dysthymia who seek help at a time of loss or role transition in their lives. Knowledge of the interpersonal context of depression is obviously important in for-mulating how the clinician would stage the psychological recovery process from dysthymia. Nonetheless, there are some suggestions that SSRIs often lead to improved coping behaviour, even without formal psychotherapy. Indeed, Canadian studies have shown that a successful response to SSRIs is often associated with decreased emotion-focused coping and decreased perception of daily hassles, as well as alleviation of the sense of loneliness one experiences in chronic depression.
No matter what the active ingredients in antidysthymic treat-
ments, there is little doubt that for the ﬁ  rst time in the history of

ments, there is little doubt that for the ﬁ  rst time in the history of 
psychiatry we have potent practical treatments to alleviate a major source of chronic human suffering, including what were once deemed depressive characterological attributes inseparable from the habitual self. Helping patients attain a new homeostasis of the self is an art unparalleled in the history of medical science. In our view, it does not constitute what Kraemer has erroneously labeled ‘cosmetic psychopharmacology’ .
(32)
Prevention opportunities(20)
Community subjects with pure dysthymia have been found in two prospective studies to be at risk for major depressive episodes. Because dysthymia often makes its ﬁ  rst appearance in juvenile

Community subjects with pure dysthymia have been found in two prospective studies to be at risk for major depressive episodes. Because dysthymia often makes its ﬁ  rst appearance in juvenile 
years, identifying the disorder at this early stage represents a special opportunity for prevention in child psychiatry and paediatrics. ‘Pure’ dysthymia, even without major depression, responds better to pharmacotherapy better than to placebo in 8 out of 9 social domains. St. John’s Wort, on the other hand, does not appear to be effective in dysthymia!
(33)
In still another group of patients, low-grade chronic depressive 
developments occur in the setting of disabling systematic medical and neurological disorders, and are best categorized as ‘secondary dysthymias’ . For instance, poliomyelitis may not only lead to deformities in musculoskeletal structures in children, but could permanently scar the sufferer’s sense of enjoyment, fulﬁ  llment, and

outlook of life. Likewise, low-grade chronic depressive develop-ment often complicates neurodegenerative cerebrovascular disease later in life. In both situations, psychological factors might be operative, yet the contribution of speciﬁ  c cerebral lesions to the 
subthreshold mood disturbance may be substantial. This group as a whole is not well captured by the conventional depressive cate-gories in ICD-10 and DSM-IV . In these subacute dysthymic-like conditions, the affective state is often disabling, yet symptomato-logically less severe than major depression; it is low grade, yet not 
as chronic as dysthymia. ‘Minor depression’ would not capture the 
clinical signiﬁ  cance of their condition. Indeed, there is emerging 
data that treating these subacute dysthymias may improve the prognosis of the underlying neurological disorder.
(22)In concluding this review of the legitimacy of dysthymia from

(22)In concluding this review of the legitimacy of dysthymia from 
clinical, biologic and therapeutic standpoints, it is relevant topoint out that dysthymia—properly deﬁ  ned—may well serve as
a behavio ral endophenotype for depressive illness.
(34) Such a
conceptualization highlights its potential as a target for preventing strategies for major depressive illness.
Cyclothymic disorder and labile-irritable 
variants(20)
History
Kraepelin included the cyclothymic disposition as one of the tem-

History
peramental foundations from which manic-depressive illness arose. Kretschmer went one step further and proposed that this constitu-tion represented the core characteristic of the illness: some patients were more likely to oscillate in a sad direction, while others would more readily resonate with cheerful situations; these were merely viewed as variations in the cyclothymic oscillation between these two extremes. Kurt Schneider, who did not endorse the concept of ‘temperament’ , instead referred to ‘labile psychopaths’ whose moods constantly changed in a dysphoric direction, and who bore no relationship to patients with manic depression. T o confuse matters further, Schneider used the term ‘cyclothymia’ as a synonym for all manic depressive illness, from the mildest to the most severe psychotic forms. T oday, ‘cyclothymia’ is still sometimes used in this

broader sense in Germanophone psychiatry. But in much of the 
rest of the world, cyclothymia (short for ‘cyclothymic disorder’) is reserved for a form of extreme temperament related to bipolar disorder.
Cyclothymia, which in ICD-9 and DSM-II was subsumed under 
the affective personalities, was ﬁ  rst introduced into DSM-III and 
DSM-IV and subsequently into ICD-10 as a form of attenuated chronic mood disorder. The diagnosis is not commonly made in clinical practice, because it is almost always seen when a patient presents with major depressive episodes, warranting the designa-tion of ‘bipolar II’ . Indeed, Hecker used cyclothymia as a synonym for what today we call bipolar II; his short monograph has recently been translated into English.
(35) Nonetheless, systematic clinical 
and familial validation studies conducted in Memphis(36,37) have

and familial validation studies conducted in Memphis(36,37) have 
shown that the construct of cyclothymic temperament is of great theoretical, psychometric and practical signiﬁ  cance as one of the possible substrates for major mood disorders. Moreover, it could shed light on social and occupational maladjustment and/or addictive behaviours that could otherwise be misattributed to personality disorder.
Clinical features and diagnostic considerations(20)
By deﬁ  nition, individuals with cyclothymia report short cycles of

By deﬁ  nition, individuals with cyclothymia report short cycles of 
depression and hypomania that fail to meet the sustained duration criterion for major affective syndromes. At various times, they exhibit the entire range of manifestations required for the diagnosis of depression and hypomania, but only from a few days at a time up to 1 week, rarely longer. These cycles follow each other in an irregular fashion, often changing abruptly from one mood to another, with only rare interposition of ‘even’ periods. The unpre-dictability of mood swings is a major source of distress for cyclothymes, as they do not know from moment to moment,how they will feel. As one patient put it, ‘my moods swing like a

687
pendulum, from one extreme to another’ . The rapid mood shifts, 
which undermine the patients’ sense of self, may lead to the mis-leading diagnostic label of borderline personality. But unlike a per-sonality disorder, the mood changes in cyclothymes have a circadi-an component. One patient described it as follows: ‘I would go to bed in a cheerful mood and wake up down in the dumps’ . This observation is in line with NIMH psychophysiological data on mood-switching occurring out of the rapid eye movement sleep phase, as reported in more typical cases of manic depression.
The mood swings of cyclothymes are biphasic: eutonia versus 
anergic periods; people-seeking versus self-absorption; sharpened thinking versus mental paralysis. Table 4.5.9.5 provides an empiri-cally tested set of criteria. In addition, the following presentations characterize their roller-coaster biography.
Irritable periods . At one time or another, labile angry or irritable

Irritable periods . At one time or another, labile angry or irritable 
moods are observed in virtually all these patients. Cyclothymes, unlike patients with epilepsy, are aware of their ‘ﬁ  ts of anger’ , which 
lead to considerable personal and social embarrassment after they subside. The patients often feel ‘on edge, restless, and aimlessly driven’; family and friends report that during these periods patients seem inconsiderate and hostile toward people around them. The contribution of alcohol and sedative-hypnotic drugs to these moods cannot be denied, but the moods often occur in the absence of drugs. Electroencephalography typically reveals no seizure or subseizure activity. The interpersonal costs of such unpredictable interpersonal explosiveness can be quite damaging. One of our patients reported frequent periods where he would start unpro-voked ﬁ  ghts with very close friends, only to shift into periods of

prolonged ‘soul-searching, guilt, shame, and embarrassment’ . In other patients, outbursts of anger are ‘reactive’ to minor inter-personal disputes—but once in full force, they are like emotional avalanches with the distinct potential to destroy relationships. Should they dominate the clinical picture, especially among young women who hurt themselves in response to interpersonal contexts, the problematic diagnosis of borderline personality disorder is often invoked (more so in North America than elsewhere). Although controversial, contemporary research suggests that many ‘borderline’ patients represent a severe labile-irritable variant of cyclothymia on the border of manic-depressive psychosis.
(38)
On the other hand, bizarre episodes of self-harm with features of post-traumatic stress are uncharacteristic of cyclothymia, and suggest other diagnoses.
Romantic–conjugal failure . It is easy to understand how indi-

viduals with mercurial moods would charm others when in an expansive people-seeking mode, and rapidly alienate them when dysphoric. In effect, the life of many of these patients is a tempestu-ous chain of intense but brief romantic liaisons, often with a series of unsuitable partners. Some rationalize their behaviour on the 
grounds that their spouse or partner is ‘too conservative in sex, too unimaginative, too unaware of the intensity’ needed to stimulate 
them. As expected, frequent marital separations, divorces, and remarriage to the same person occur.
Financial extravagance . One patient in our case series reported 
going to bars and buying people drinks because he wanted every-body to feel like him. Another patient intermittently showered his lovers with expensive jewellery. In general, however, the extrava-gance of the cyclothymic group reﬂ  ects gregariousness and tends

to occur on a smaller scale compared to the psychotic manner in which manic patients bring ﬁ  nancial ruin to themselves and their 
families.
Uneven school and work record . Repeated and unpredictable

families.
Uneven school and work record . Repeated and unpredictable 
shifts in work and study habits occur in most people with cyclothymia, giving rise to a dilettante biography. Although some do better during their ‘high’ periods—for example, one car sales-man would sell cars only ‘when up’—for others, the occasional ‘even’ periods were more conducive to meaningful work. It is sometimes unappreciated by clinicians inexperienced withbipolarity that the hypomanic period can be one of disorganized and unpatterned busyness that could easily lead to a serious drop in net productivity. For instance, one insurance salesman related that he was less successful when ‘high’ , because he tended to enter into unproductive arguments with his clients. When ‘down’ ,productivity obviously abates, although two creative individuals in our case series—one inclined poetically, the other towards painting—produced their better work when coming out ofmini-depressions.

Alcohol and drug abuse . An alternating pattern of the use of 
‘uppers’ and ‘downers’ occurs in at least 50 per cent of patients. We have clinically evaluated at least ﬁ  ve cyclothymes who ‘sold 
dope’ to maintain their habit: two went to prison. These and other 
observations suggest that a proportion of substance-abusing, 
especially stimulant-abusing, patients might be suffering from subtle or cryptic forms of bipolar disorder. The bipolar nature of mood swings in alcohol- or substance-abusing individuals can be documented by demonstrating mood swings well past the period of detoxiﬁ  cation; in some cases, escalating mood instability makes 
its ﬁ rst appearance following abrupt drug or alcohol withdrawal. 
The DSM-IV criteria for drug-induced or drug withdrawal-induced mood disorder are, in our opinion, biased against the diagnosis 
of otherwise treatable bipolar spectrum disorders. New evidence

of otherwise treatable bipolar spectrum disorders. New evidence 
suggests that the temperamental disorder might serve as the anlage for self-enhancement or augmentation with cocaine, other stimu-lants and heroin.
(39,40) These features might raise differential diag-
nostic questions from adult attention deﬁ  cit hyperactivity disorder 
(ADHD). The social warmth observed among most people with cyclothymia distinguishes them from ADHD. Also, elation and inﬂ ated self-conﬁ  dence, which occur periodically in cyclothymia, 
are uncharacteristic of ADHD; the moodiness in the latter is largely 
depressive in nature. Finally, antidepressants and stimulants typically 
worsen the moods in cyclothymia; they treat ADHD. In rare cases, however, cyclothymia and ADHD can coexist.
Course patterns
In cyclothymia, hypomania and mini-depression alternate with

In cyclothymia, hypomania and mini-depression alternate with 
each other from adolescence. For instance, the optimistic, over-Table 4.5.9.5  Discriminatory biphasic characteristics of cyclothymic 
disorder*
Lethargy alternating with eutonia
Shaky self-esteem alternating between low self-conﬁ  dence and overconﬁ  denceDecreased verbal output alternating with talkativenessMental confusion alternating with sharpened thinking
Introverted self-absorption alternating with uninhibited people-seeking
*Summarized from Akiskal et al.
(36,37)4.5.9 dysthymia, cyclothymia, and hyperthymia

SECTION 4  clinical syndromes of adult psychiatry 688
conﬁ  dent, people-seeking phase can give way to self-absorption, 
self-doubt, pessimism, and a sense of futility, emptiness, and suicidal ideation. More commonly, depressive periods dominate the clinical picture, interspersed by ‘even’ , ‘irritable’ , and occasional hypomanic periods. Indeed, most people with cyclothymia who present clinically do so because of depression. These depressions are typically short-lived, yet unrelenting in their cyclic course, cre-ating much interpersonal havoc for the patient. The following 
vignette illustrates the cardinal clinical features of cyclothymia that 
has not yet progressed to major depression.
Case Study:  This 24-year-old songwriter presented with the 
chief complaint of ‘depression so bad that I become totally dysfunc-tional—I cannot even get out of bed’ . Since her mid-teens she had

chief complaint of ‘depression so bad that I become totally dysfunc-tional—I cannot even get out of bed’ . Since her mid-teens she had 
experienced periods lasting from a few days up to a week, during which she would withdraw into herself, losing conﬁ  dence and 
interest, feeling drained of energy, and crying when approached by anybody. These periods were particularly prevalent during the autumn and winter months, but they did not coincide with the premenstrual phase. All she needed sometimes was restful sleep to ‘feel alive again’; at other times, she would have little sleep, and would wake up ‘wired’ , ‘ready to go’ , ‘open to experience all the joy waiting for me out there’; she would exude conﬁ  dence, ‘sensuality

and sexual aroma’ . These occurred less frequently than the ‘down’ periods and usually lasted for 1 to 3 days, but were not associated with creative spurts. The latter came as she was descendingfrom ‘highs’ into a more ‘mellow depression’ . Her success in music had been sporadic, paralleling the sporadic nature of her ‘muses’ that visited her on the descending limb of ‘hypomania merging with tears’ . However, the major toll of her mood swings hadbeen in her personal life, the intensity of her moods had driven away most men she had loved, of whom she had lost count. She described periods of such intense sexual arousal, that sometimes she would go to bed ‘with anybody, including women of allages, shapes, and description’ . But, she added: ‘I am not a lesbian—oral love is just one way of relating to these women—why not?’ She had also experimented with drug s, such as stimulants, which had 
made her moodiness worse. More recently, she had been prescribed

made her moodiness worse. More recently, she had been prescribed 
at least two SSRIs, which after a period of ‘success’ for a few months, 
had made her depressive swings more frequent and lower inamplitude, leading to the present consultation in our clinic.
As documented in this case, sexual excesses with both sexes 
are often readily admitted by patients. Winter accentuation or 
clustering of depressive periods, as exempliﬁ  ed here, is not uncom-
mon in cyclothymia. We also would like to point out the special relationship of the moods to artistic productivity which occur in up to 8 per cent of cyclothymic depressions.
(41) The 4-day thresh-
old for hypomania in the ofﬁ  cial diagnostic manuals is too con-

servative; as shown in this case, most patients with cyclothymia (and bipolar II disorder) report a threshold of 1 to 3 days (though on occasion, one would observe a hypomanic duration of 1 week or longer). It is also noteworthy that the episodes are short-lived and do not reach the duration threshold for rapid cycling. Sometimes, the term ‘ultra rapid cycling’ is used for these patients, but we prefer to reserve this for extremely severe cases who require hospitalization. T he short cycle length in cyclothymia is, in part, a 
selection artifact: the universe of patients with bipolar disorder is composed of an extreme variety of overlapping patterns.The relationship of a cyclothymic temperament to the bipolar

selection artifact: the universe of patients with bipolar disorder is composed of an extreme variety of overlapping patterns.The relationship of a cyclothymic temperament to the bipolar 
spectrum is more complex than that of dysthymia to majordepressive disorder. Although cyclothymia can be observed in some patients with full-blown manic-depressive illness (bipolar I with severe or hospitalized mania), it is more commonly associated with the bipolar II pattern (of recurrent major depression with self-limited hypomanias). In a recent French national study of patients with major depression, 88 per cent of those with a cyclo-thymic disposition belonged to the bipolar II subtype. (Mania, by contrast, has been reported to more likely represent either an extension of hyperthymic traits, or a reversal from a depressive temperamental baseline.)
One-third of patients with cyclothymia studied by us on a pro-

spective basis, progressed to spontaneous affective episodes with more protracted hypomanias and clinical (major) depression.
(36,37)
Thus, 6 per cent of the original cyclothymic cohort could be reclas-siﬁ ed as bipolar I, and 30 per cent as bipolar II. The tendency to 
switch to hypomania was further augmented by the administration of antidepressants. A larger National Institute of Mental Health study of patients with major depression who switched to bipolar II during a prospective observation period of up to 11 years, found that a temperamental mix of ‘mood-labile’ , ‘energetic-active’ , and ‘daydreaming’ traits (reminiscent of Kretschmer’s concept of the cyclothymic temperament were the most specific predictors of such outcome. Actually such temperamental factors predict who among the offspring of bipolar probands will progress during prospective course to clinical episodes.
(42) New data further indi-

cate that cyclothymia might be one of the pathways to suicidality among adolescents.
(42)
The foregoing clinical and course characteristics suggest that
a cyclothymic temperament leading to major depressive recur-
rences represents a distinct longitudinal pattern of ‘cyclothymic depression’ , and which appears to capture the core features of 
bipolar II disorder in contemporary clinical practice. Because hypomanic episodes cannot be easily ascertained by history, assessing cyclo thymia in clinically depressed patients representsa more sensitive and specific approach to the diagnosis ofbipolar II.
An excess of interpersonal difﬁ  culties and psychiatric consultations

An excess of interpersonal difﬁ  culties and psychiatric consultations 
distinguish people with cyclothymia in the community from controls; excessive use patterns of stimulants, caffeine, nicotine, and alcohol, have also been well documented. Explosive traits, probably representing the irritable component of cyclothymia, have been reported to be prevalent in the community in a British study. More recently, we found that 6.3 per cent of a national cohort of 1010 Italian students between the ages of 14 and 26 years ofage scored above two standard deviations for cyclothymia; this was more prevalent in females, with a ratio of 3:2. Overall, the foregoing data testify to the fact that a cyclothymic and/or labile disposition can be accurately measured, is prevalent, and represents a population at risk for affective disorders. Table 4.5.9.6 summa-rizes the rates in different populations.
Aetiological aspects
The ﬂ  amboyant behaviour and the restless pursuit of romantic

The ﬂ  amboyant behaviour and the restless pursuit of romantic 
opportunities in cyclothymia suggest the hypothesis that its

689
constituent traits may have evolved as a mechanism in sexual selec-
tion.(23) Even their creative bent—in poetry, music, painting, or 
fashion design—may have evolved to subserve such a mechanism. Cyclothymic traits appear to lie on a polygenic continuum between excessive temperament and manic depression. Indeed, clinically identiﬁ  ed cyclothymes have patterns of familial affective illness, as 
one would expect for a forme fruste  disorder.
Cyclothymia has also been observed in the offspring of manic-
depressive probands, with onset in the postpubertal period.Finally, family studies of patients with a bipolar disorder have revealed an excess of cyclothymia. Hypothetically, this tempera-ment might represent one of, if not the most important, inherited trait diathesis for bipolar disorder. For instance, moody-temperamental individuals are over-represented in the ‘discordant’ monozygotic co-twins of Danish manic-depressives. Alternatively,

and in a more theoretical vein, manic-depressive illness might
be the genetic reservoir for the desirable cyclothymic traits in the population at large.
(23,44)  In line with these data and consider-
ations, cyclothymia can be considered a behavioral endophenotype for bipolar disorder.
(45) This is supported by recent ﬁ  ndings from 
both Europe and the United States which have shown that it is present in the clinically well relatives of bipolar probands. Cyclothymia might also share familial-genetic relationship with alcohol and substance use,
(40) bulimic,(46) panic,(47) obsessive-
compulsive(48) as well as atypical depressive and borderline
conditions.(49)
Clinical management
The proper pharmacological treatment for cyclothymic excesses is low doses of lithium (600–900 mg/day) or valproate (500–750 mg/day). These are based on open systematic studies.
(50) There

(50) There
is some data from a controlled trial with lithium about theprevention of depression in cyclothymic individuals. Similarly controlled data exist for a related construct—‘labile personality’ . 
Generally speaking , patients with cyclothymia object to the
‘overcontrol’ that may come from mood stabilizers, and this is particularly the case with lithium. Lamotrigine is also beingused on clinical grounds in the unstable dysthymic-cyclothymic spectrum. In those with ‘borderline’ features, lamotrigine isparticularly promising.Patients should be taught how to live with the extremes of their

temperamental inclinations, and to seek professions where they determine the hours that they work. Marriage to a work-oriented or a rich older spouse might sustain them for a while, but eventually interpersonal friction and sexual jealousy terminate such marriag-
es. The artistically inclined among them should be encouragedto live in those parts of a city inhabited by artists and otherintellectuals, where temperamental excesses are better tolerated. 
ltimately, the decision to use mood stabilizers in such individuals should balance any beneﬁ  ts from decreased mood instability

ltimately, the decision to use mood stabilizers in such individuals should balance any beneﬁ  ts from decreased mood instability 
against the social and creative spurts that the cyclothymic disposi-tion can bring to them. Their clinical management represents a challenging task for the psychiatrist who is willing to learn about the lifestyle of these individuals, not prejudging them by the more mundane norms of society. But the psychiatrist should alsobe there to help them during the multiple crises of their lives.Low-dose sedating neuroleptics, both classical (e.g. thioridazine 50 mg at bedtime) and atypical (e.g. quetiapine 25–50 mg atbedtime) may temporarily help to diffuse such crises. It is only when a clinician has earned therapeutic alliance with a patient that the latter will permit limit-setting on his or her extravagant or outrageous behaviour. Parents might also beneﬁ  t from some

counselling, because the dilettante life of their children is often a source of great sorrow for them. Rarely, parents or spouses are rewarded by great artistic or intellectual achievement, which does not necessarily reduce the pain that the volatile cyclothymes bring to their loved ones.
Kurt Schneider admonished the kin of labile individuals (who 
might approximate the contemporary concept of borderlinepersonality disorder) ‘on their bad days . . . to keep out of their way as far as possible’ . Cyclothymes with some insight into their own 
temperament would give the same advice to their loved ones.
A cautious trial of anticonvulsants will often prove effective in those distressed enough by their behaviour to comply with such treatment.

The offspring of patients with bipolar disorder who exhibit a cyclo-thymic level of temperamental dysregulation represent a logical population for prevention studies. This is a challenge for the 21st century. Presumably molecular genetic testing will one day identify those moody individuals who carry the genes for bipolar disorder. At present, it would be useful to conservatively follow-up the cyclothymic offspring of people with bipolar disorders and provide them with psychoeducation about the necessity of avoiding stimulants and sleep deprivation. It may not be entirely possible to prohibit the use of occasional alcohol consumption, but benzodiazepines should not be used. It is also imperative, should they get depressed, to protect them from the indiscriminate pre-scription of antidepressants.

Mood-labile female prisoners, commonly given the diagnosis of 
antisocial or borderline personality disorder, may represent affec-
tive variants with irritable cyclothymic features. Formal studies are needed in prison populations, to assess more precisely the rates of preventable cryptic bipolarity among female and male offenders.
It is ﬁ  nally worthwhile to mention that affective temperaments 
with irritable, cyclothymic and irritable-hyperthymic traits might predispose to HIV infection. The public health dimensions of this question deserve further research focus.Table 4.5.9.6  Prevalence of cyclothymic and related mood-labile 
temperaments
(20)*
Reference Population (Country) Rate (%)
Akiskal et al. (1977) Mental health centre (USA) 10
Weissman and Myers (1978) Community (USA) 4Depue et al. (1981) College students (USA) 6
Casey and Tyrer (1986) Community (UK) 6Wicki and Angst (1991) Community (Zurich) 4Placidi et al. (1988) 14–26–year old students (Italy) 6

*These data derive from interview-based studies. For more recent psychometric 
data based on cyclothymic and a broader range of sub-bipolar temperaments in 
a self-reported format can be found in a new monograph.
(8)4.5.9 dysthymia, cyclothymia, and hyperthymia

SECTION 4  clinical syndromes of adult psychiatry 690
The hyperthymic temperament(38)*
History and description
Although well described by classical German psychiatrists
(e.g. Schneider), the hyperthymic type appears neither in DSM-IV nor in ICD-10. A lifelong disposition, hyperthymia must bedistinguished from short-lived hypomanic episodes. Alternatively, this disposition can be characterized as trait hypomania. It derives from the ancient Graeco-Roman sanguine temperament, believed to represent the optimal mixture of behavioural traits. They are full of zest, fun-loving, and prone to lechery: their habitual disposition is one of buoyant action-orientation, extraverted people-seeking, overconﬁ  dence, and swift thinking. Typically short sleepers, they 
possess boundless energy to invest in sundry causes and projects, 
which often earn them leadership positions in the various profes-

sions and politics, yet their carefree attitudes and propensity for risk-taking can bring them to the brink of ruin; this is particularly true for their ﬁ  nances and sexual life, which can be marred by scan-
dal. A hyperthymic lifestyle is so reinforcing that some resort to ‘augmenting’ it with stimulants such as amphetamines or cocaine. In brief, while a hyperthymic temperament per se  does not consti-
tute affective pathology—indeed, it represents a constellation of adaptive traits—in excess it could lead to undesirable complica-tions. The latter will be our main focus here.

The foregoing considerations partly explain why such a tempera-ment has received scant research attention in the community. Extrapolating from studies on intermittent hypomania in the community, if strictly limited to hypomania with early onset and persistent course, the prevalence of hyperthymic temperament can be estimated to be slightly under 1 per cent. On the other hand, the traits that constitute the hyperthymic proﬁ  le are so desirable that 
normal individuals tend to endorse them; in a recent Pisa-San Diego collaboration
(16) involving 1010 students aged between 14 
and 26, of whom 8.2 per cent met the full criteria for hyperthymic temperament, all participants scored between the ﬁ  rst and second 
positive standard deviation. The TEMPS-A tends to validate these ﬁ ndings in Lebanon,

(51) Argentina(52) and Hungary.(53) More work 
needs to be done on the psychometric standardization of this tem-peramental construct; on the other hand, all studies are consistent in showing marked male predominance.
Diagnostic aspects
On the positive side, hyperthymic individuals are enterprising, ambitious, and driven, often achieving considerable social and voca-tional prominence. Abuse of stimulants is not so much an attempt to ward off depression and fatigue as an effort to enhance their already high-level drive and, sometimes, to further curtail their already reduced need for sleep. Hyperthymic individuals typically marry three or more times. Others, without entering into legally sanctioned matrimony, form three or more families in different cit-ies; these men are capable of maintaining such relationships for long periods, testifying to their ﬁ  nancial and personal resourcefulness, as

well as their generosity towards their lovers and the offspring from such unions. Unlike the antisocial psychopath who is predatory on others and neglects or abuses his women and children, these men 
care for their loved ones. But obviously, the ‘arrangement’ involving women of different generations is complex, and a fertile soil for jeal-ousy, drama, scandal, and tragedy. Nonetheless, it is not uncommon to see more than three or four women crying profusely and express-ing their common grief at the funerals of these men!
Although individuals with hyperthymia optimally enjoy the 
advantage of their reduced need for sleep (giving more time and energy to invest in work and pleasure), some present clinically because of insomnia. Thus, in a predominantly male sample of exec-utives presenting to a sleep centre,
(54) habitual sleep need was

(54) habitual sleep need was 
4 to 5 h; however, they had been intermittently bothered by ‘nervous energy’ and difficulty falling asleep. Now, in late middle age, alcohol was no longer an effective hypnotic. Although they vigor-ously denied depressive and other mental symptoms—indeed, they had extremely low scores on self-rated depression—spouses or lovers provided collateral information about brief irritable-depressive dips, especially in the morning and, in some cases, more protracted ‘fatigue states’ of days to weeks during which the subject would vegetate. Despite these depressive dips, these patients were distinguished from the constantly shifting moods of cyclothymic patients by the fact that the depressions arose from a baseline of trait hypomania of a moreor less stable course. Our most current diagnostic guidelines fora hyperthymic temperament consist of the following traits on a habitual basis since at least early adulthood: cheerful, overoptimistic,

or exuberant; extraverted and people-seeking, often to the point of 
being overinvolved or meddlesome; overtalkative, eloquent, andjocular; uninhibited, stimulus-seeking, and sexually-driven; vigor-ous, full of plans, improvident; overconﬁ  dent,  self-assured, and 
boastful attitudes that may reach grandiose proportions.
A systematic retrospective review of the case records of people

A systematic retrospective review of the case records of people 
with manic depression, whose course was dominated by manic episodes, was recently undertaken in Munich, yielding attributes overlapping with our proposed list: active, vivid, extraverted, verbally aggressive, self-assured, strong willed, engaged in self-employed professions, risk-taking, sensation-seeking, breaking social norms, spendthrift, and generous. The fact that at least 10 per cent of patients with major depression in an Italian study could be characterized as premorbidly hyperthymic, suggests that this temperament has relevance to both major affective poles. This is an important diagnostic consideration, because rather than being considered narcissistic depressions, these should be recognized as a soft bipolar variant.
It is of interest that Gardner’s ethological analysis(55) of what

It is of interest that Gardner’s ethological analysis(55) of what 
constitutes ‘leadership’ led to a description that overlaps with a hyperthymic proﬁ  le: cheerfulness, joking, irrepressible infectious 
quality, unusual warmth, expansive, strong sense of conﬁ  dence in 
one’s abilities, scheming, robust, tireless, pushy, and meddlesome. Hypothetically, this temperament evolved in primates whose social life required leadership to better face challenges to the group from within and without.
In a sleep electroencephalography study,
(54) REM latency was 
found to be shortened; similar ﬁ  ndings have been reported on the 
sleep of manic patients, thereby supporting the notion of a trait-state continuum at the neurophysiological level. (Although counter-intuitive, this neurophysiological marker appears to be shared between the depressive and hyperthymic poles.) Finally, family
* Unless otherwise speciﬁ  ed, this review article contains most of the

* Unless otherwise speciﬁ  ed, this review article contains most of the 
references to the concepts, history, and research on the hyperthymic type.

691
history for frank bipolar disorder characterizes many such individu-
als. The foregoing data, albeit limited, suggest that hyperthymic traits share several key biol ogical underpinnings of affective
disorder.
Course and treatment
Little is known about the natural course of the hyperthymic temperament, except what can be reconstructed retrospectively from biographical and clinical studies. Given their overoptimistic and self-assured style of thinking, these individuals feel perfectly ﬁ  t 
in all areas of functioning and thus have no need to consult a psy-chiatrist. They do so only when forced by loved ones. There are no systematic treatment studies on hyperthymia. Anecdotally,
(50) low

(50) low 
doses of anticonvulsants such as valproate (e.g. 500–750 mg/day) can be useful in reducing drivenness, when deemed appropriate on clinical grounds, such as in the presence of cardiovasculardisease, or when enormous sexual appetite places them at risk forsocial scandals and, in some cases, exposure to HIV infection.
(56)
Stimulant-abusing subjects with hyperthymia can be detoxiﬁ  ed 
with valproate, carbamazepine, or gabapentin. Clinically depressed subjects with a hyperthymic temperament often respond poorly to antidepressants. In our opinion, the efﬁ  cacy of lithium augmenta-
tion in resistant depression is partly based on the high prevalence of hyperthymia in resistant populations; it would be wise to keep the dose of lithium in augmentation in such individuals to a lower to middle range (i.e. 600–900 mg/day).
People with hyperthymia are action-oriented, and are not

People with hyperthymia are action-oriented, and are not 
inclined to any type of self-examination. Furthermore, their hypertrophied sense of denial makes them poor candidates for psychotherapy. The physician must, nonetheless, attempt psycho-education about the harm that can come to them and their loved ones because of their temperamental excesses. Alcohol consump-
tion, which is common in these individuals, should not be abruptly 
interrupted because of the risk of the switch to a suicidal depression. If detoxiﬁ  cation is necessary for health reasons, admission to a 
suitable inpatient facility should be arranged. The occasion might be proﬁ  tably used for whatever counselling is deemed appropriate 
for life and health situations confronting them at the time.
Therapeutic and preventive aspects
In clinical practice, hyperthymic indi viduals are likely to  be confused

with narcissistic or antisocial types. Otherwise, they rarely present to psychiatrists, except as the premorbid adjustment of manic-depressive illness. Hyperthymic individuals are often the driving force of society in economic and political life and unless they are involved in scandals or suicidal behavior, rarely come to the atten-tion of clinicians. In the rare circumstances they seek psychiatric advice, it is due to exasperated pressure from loved ones; even then, they tend to dictate rather than follow treatment recommenda-tions. Their sense of entitlement derives in part from the fact these individuals have considerable leadership talent and often bequeath large sums of endowments for research, museums and other community projects. Some are performing artists. Others are famed for their erotic life in the tabloid and popular press. Rare biological investigations have been conducted on hyperthymia involving 
fascinating neurophysiologic and endophenotype studies.
(57,58)

(57,58)
The preventive potential of such investigations for manic-depressive illness remains uncertain at this time.Further information
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4.6
Stress-related and 
adjustment disorders
4.6.1 Acute stress reactions
Anke Ehlers, Allison G. Harvey, 
and Richard A. Bryant
Exceptionally stressful life events can cause severe psychological 
symptoms, including anxiety, feelings of derealization and depersonalization, and hyperarousal. In one of the ﬁ  rst studies to 
comprehensively document acute reactions to extreme stress, Lindemann
(1) observed that the symptoms reported by survivors 
of the Coconut Grove Fire included avoidance, re-experiencing scenes from the ﬁ  re, reports of derealization, and the experience of 
anxiety when exposed to reminders of the event. Similarly, acute responses reported by soldiers who fought in the First and Second World Wars included re-experiencing symptoms and dissociative 
responses such as numbing, amnesia, and depersonalization.
(2)
The International Classiﬁ  cation of Diseases  has recognized acute 
stress reactions since 1948 (ICD-6).(3) In the most recent edition

(2)
stress reactions since 1948 (ICD-6).(3) In the most recent edition 
(ICD-10),(4) early reactions to exceptionally stressful life events are 
diagnosed as acute stress reaction, one of the diagnoses in the sec-tion headed ‘reactions to severe stress, and adjustment disorders’ .In contrast, the Diagnostic and Statistical Manual of Mental 
Disorders did not formally recognize that exceptionally stressful life 
events are a sufﬁ  cient cause of psychological symptoms until 1980 
when its third edition (DSM-III)
(5) introduced the diagnosis of 
post-traumatic stress disorder ( PTSD ). DSM-III did not stipulate 
a duration for the symptoms, but the revised third version (DSM-III-R)
(6) required that the symptoms of PTSD must be present for

(6) required that the symptoms of PTSD must be present for 
more than 1 month after the traumatic event. This stipulation pre-cluded the inclusion of acutely traumatized individuals who instead were diagnosed with adjustment disorder.
(7) In 1994 the fourth 
edition of DSM (DSM-IV)(8) formally recognized acute trauma 
reactions by introducing the new diagnosis of acute stress disorder into the anxiety disorders section.
The diagnoses of acute stress reactions in ICD-10 and of acute 
stress disorder in DSM-IV have similarities in that they are caused by extreme stress and have some overlap in symptom patterns. They can be considered as two separate points on a continuum from transient to more enduring symptoms. However, there are also differences in the underlying concepts, as we will discuss in this chapter.

Acute stress reactions, as deﬁ  ned in ICD-10, are transient reactions 
to exceptional physical and/or mental stress. There is an initial stage of a ‘daze’ , including narrowing of attention, inability to compre-hend stimuli, and disorientation. This is followed by a rapidly changing picture of symptoms that may include withdrawal from the surrounding situation, ﬂ  ight reactions, panic anxiety, and 
autonomic hyperarousal, depression, anger, or despair. Symptoms usually begin to diminish after 24 to 48 h and should be minimal after about 3 days.
In contrast, acute stress disorder, as deﬁ  ned in DSM-IV , is only 
diagnosed if the psychological symptoms persist for more than 2 days. Dissociative symptoms dominate the disorder. Dissociation refers to a disruption of the usually integrated feelings of con-sciousness, memory, identity, or perception of the environment. 
Symptoms include a subjective sense of numbing or detachment,

Symptoms include a subjective sense of numbing or detachment, 
reduced awareness of surroundings, derealization, depersonaliza-tion, or dissociative amnesia. In addition, patients with acute stress disorder experience symptoms that are typical of PTSD, namely re-experiencing aspects of the event, avoidance of reminders of Contents
  4.6.1 Acute stress reactions
  4.6.2 Post-traumatic stress disorder
  4.6.3 Recovered memories and false memories
  4.6.4 Adjustment disorders
  4.6.5 Bereavement

SECTION 4  clinical syndromes of adult psychiatry 694
the event, and hyperarousal symptoms. Acute stress disorder is seen 
in DSM-IV as a precursor of PTSD. If the re-experiencing, avoid-ance, and hyperarousal symptoms persist for more than 4 weeks, PTSD is diagnosed.
ICD-10 classiﬁ  es acute stress reactions (F43.0) among the reactions 
to severe stress and adjustment disorders (F43) that are primarily caused by stressful events. DSM-IV classiﬁ  es acute stress dis-
order (308.3) among the anxiety disorders, like PTSD (see also Chapter 4.6.2).
The main diagnostic criteria for acute stress reactions(ICD-10) and acute stress disorder (DSM-IV) are compared in Table 4.6.1.1.
Stressor criterion
Both ICD-10 and DSM-IV require that acute stress responses must occur in the immediate aftermath of an exceptionally stressful event. ICD-10 uses a broad concept of what qualiﬁ  es as an ‘excep-

tional mental or physical stressor’ . This includes stressors that would be regarded as traumatic (e.g. rape, criminal assault, natural catastrophe) as well as unusually sudden changes in the social position and/or network of the individual (e.g. domestic ﬁ  reor multiple bereavement). In contrast, DSM-IV uses a narrow
deﬁ nition of stressors that lead to acute stress disorder, which is

deﬁ nition of stressors that lead to acute stress disorder, which is 
identical to the stressor criterion of PTSD. It requires (i) that the traumatic event must have involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others, and (ii) that the person’s response to the traumatic event must have involved intense fear, helplessness, or horror (or disorganized or agitated behaviour in children) (see Chapter 4.6.2 for the rationale underlying this deﬁ  nition).
Symptom patterns
As shown in Table 4.6.1.1, the diagnostic criteria for acute stress 
reactions (ICD-10) and acute stress disorder (DSM-IV) overlap, in that they include symptoms of dissociation, anxiety, and hyper-arousal. DSM-IV puts a much greater emphasis on dissociation, requiring a minimum of three of the dissociative symptoms speci-ﬁ ed in Table 4.6.1.1 (Criterion B). According to ICD-10, any

combination of a minimum of four symptoms of generalized anxiety disorder (speciﬁ  ed in Criterion C, Table 4.6.1.1) would be 
sufﬁ cient to establish the diagnosis of acute stress reaction. In addi-
tion, DSM-IV , but not ICD-10, requires the individual to have at least one re-experiencing symptom, to show marked avoidance of reminders of the trauma, and to experience signiﬁ  cant distress 
or impairment of functioning.
In contrast to DSM-IV , ICD-10 distinguishes between mild, 
moderate, and severe forms of acute stress reactions on the basis 
Table 4.6.1.1  Comparison of the criteria for acute stress reaction (ICD-10) and acute stress disorder (DSM-IV)
Acute stress reaction (ICD-10 research diagnostic criteria) Acute stress disorder (DSM-IV)
Stressor Exposure to exceptional mental or physical stress (1) Exposure to event involving actual or threatened death or serious 
  injury to self or others
(2) Experience of fear, helplessness, or horror

injury to self or others
Symptoms Criterion C: Symptoms of generalized anxiety disorder 
 (at least 4 symptoms)
Palpitations, sweating, trembling, dry mouth, difﬁ  culty 
 breathing, choking, chest pain, nausea, dizziness, 
 derealization or depersonalization, fear of losing control,  fear of dying, hot ﬂ  ushes, numbness or tingling, muscle 
 tension, restlessness, keyed up, difﬁ  culty swallowing, 
 exaggerated startle response, difﬁ  culty concentrating,  irritability, difﬁ  culty getting to sleep
Criterion C: Additional symptoms to  determine severity
Social withdrawal, narrowed attention, disorientation, 
 aggression, hopelessness, overactivity, excessive griefCriterion  B: Dissociation (at least 3 symptoms)
Numbing, reduced awareness, derealization, depersonalization, dissociative 
 amnesia
Criterion C: Re-experiencing  (at least one symptom)  Recurrent images,

 amnesia
Criterion C: Re-experiencing  (at least one symptom)  Recurrent images, 
 thoughts, dreams, illusions, ﬂ  ashbacks, reliving, distress on exposure
Criterion D: Marked avoidance
Avoidance of thoughts, feelings, conversations, activities, places, people 
 associated with the trauma
Criterion E: Marked anxiety or  increased arousal
Difﬁ  culty sleeping, irritability, poor concentration, hypervigilance, exaggerated 
 startle response, motor restlessness
Criterion F: Clinically signiﬁ  cant distress or impairment in functioning
Time from trauma Onset within 1 h Onset within 4 weeks; lasts for at least 2 daysTime course Transient; symptoms begin to diminish within 48 h May result in post-traumatic stress disorderRelationship to 
 post-traumatic  stress disorderAlternative diagnosis Precursor
Diagnostic group Reactions to severe stress Anxiety disorder

post-traumatic  stress disorderAlternative diagnosis Precursor
Exclusion criteria No other concurrent (within last 3 months) mental 
 or behavioural disorder, except for generalized 
 anxiety disorder or personality disorder(1) Not due to effects of a substance or general medical condition
(2) Not better accounted for by brief psychotic disorder
(3) Not merely exacerbation of pre-existing Axis I or Axis II disorder

695
of additional symptoms (Criterion C, additional symptoms, 
Table 4.6.1.1) such as social withdrawal, hopelessness, or excessive grief. A mild severity is stipulated when none of these symptoms are present, moderate when two are reported, and severe when four are reported or when there is dissociative stupor.
Time course of symptoms
The two diagnoses cover distinct periods on a continuum from transient to more persistent symptoms. Specifically, to meet the criteria for an acute stress reaction (ICD-10), symptoms must be manifest within 1 h of the stressor (Criterion B) and begin to diminish after no more than 8 h for a transient stressor and after no more than 48 h for an enduring stressor (Criterion D).
The diagnostic criteria for acute stress disorder (DSM-IV) 
require that the disturbance must last for a minimum of 2 days and a maximum of 4 weeks post-trauma, after which a diagnosis of PTSD can be considered.
Assessment instruments

There are two recognized clinician-administered and two self-report measures of acute stress disorder (DSM-IV) available. As yet, there are no established standardized assessment instru-ments for transient acute stress reactions (ICD-10).
(a) Acute stress disorder interview
This structured clinical interview establishes the presence or absence of 19 symptoms of acute stress disorder.
(9) The sum of the 
symptoms scored as being present indicates acute stress disorder severity. This measure has very good internal consistency ( r = 0.90), 
and, with clinician-based diagnoses as the criterion, very good sensitivity (91 per cent) and speciﬁ  city (93 per cent). T est–retest 
reliability is strong ( r = 0.88).
(b) Structured clinical interview for DSM-IV (SCID(10))

The SCID interview indexes the presence, absence, or subthresh-
old presence of each acute stress disorder symptom speciﬁ  ed in
DSM-IV . An advantage of employing this interview is that itprovides a comprehensive assessment of the differential diagno-ses and comorbid disorders that can be present in traumapopulations.
(c) Stanford acute stress reaction questionnaire(11)
This self-report inventory asks patients to rate the frequency of a range of dissociative, intrusive, somatic anxiety, hyperarousal, attention disturbance, and sleep disturbance symptoms. The ques-tionnaire has very good internal consistency (Cronbach’s alpha = 0.90 and 0.91 for dissociative and anxiety symptoms, respectively) and concurrent validity with scores on the Impact of Event Scale (r = 0.52 to 0.69).
(12,13)  It can be employed as a measure of the

(12,13)  It can be employed as a measure of the 
severity of symptoms, but does not allow the diagnosis of acute stress disorder to be established as it has not yet been validated against clinician diagnoses.
(d) Acute stress disorder scale(14)
This self-report scale is scored on a 5-point scale that reﬂ  ects degree 
of severity of 19 acute stress disorder symptoms. The Acute Stress Disorder Scale possesses good sensitivity (95 per cent) and speci-ﬁ city (83 per cent) relative to the Acute Stress Disorder Interview. 
T est–retest reliability with a re-administration interval of 2 to 7 days is strong ( r = 0.94).
(14)Differential diagnoses
Both ICD-10 and DSM-IV require that the symptoms are not 
merely an exacerbation of a pre-existing disorder. In addition, a number of alternative diagnoses need to be considered.
(a) Post-traumatic stress disorder
In ICD-10, PTSD is conceptualized as an alternative diagnosis of acute stress reactions. The deﬁ  nitions of acute stress reaction and

In ICD-10, PTSD is conceptualized as an alternative diagnosis of acute stress reactions. The deﬁ  nitions of acute stress reaction and 
PTSD differ in terms of the stressor criterion (exceptionally stressful life event versus exceptionally threatening or catastrophic event), the time course (symptoms start to diminish within 48 h versus no time limit), and symptom pattern (PTSD, but not acute stress reac-tion, includes involuntary re-experiencing the traumatic event).
In DSM-IV , acute stress disorder can be distinguished from 
PTSD by the time-frame covered by the diagnoses. Acute stress dis-order refers to the period from 2 days to 1 month post-trauma, after which a diagnosis of PTSD can be considered. The primary difference between the symptom criteria for acute stress disorder and PTSD in DSM-IV is the former’s emphasis on dissociative reactions.
(b) Adjustment disorder

This diagnosis covers a wide range of emotional or behavioural symptoms indicative of distress, which are judged to be out of proportion to the stressor experienced. This broad coverage can be contrasted with (i) the speciﬁ  c set of symptoms described by the 
acute stress disorder and acute stress reaction criteria, and (ii) the stipulation that the stressor involves both a threat to life and a subjective response of fear for the acute stress disorder and an exceptional stressor in the case of acute stress reaction.
(c) Brain injury
A number of acute stress disorder symptoms overlap with symp-toms of brain injury including reduced awareness, depersonaliza-tion, derealization, irritability, and concentration difﬁ  culties.
(15)
While results from neuropsychological and neurological investiga-

(15)
tions may assist in the differential diagnosis, there appear to be a group of individuals with a mild head injury for whom there are no known tools to differentiate whether the disturbance is due to brain injury or acute stress disorder, or whether both are present.
(d) Brief psychotic disorder
When there is one or more psychotic symptoms present after experiencing an extreme stressor, the brief psychotic disorder diag-nosis should be considered.
(e) Dissociative disorders
Given the emphasis on dissociative symptoms in acute stress disor-der, it needs to be distinguished from dissociative amnesia and depersonalization disorder. The criteria for these diagnoses stipu-late that if the amnesia or depersonalization can be accounted for by acute stress disorder then a dissociative disorder cannot be diagnosed (see Chapter 5.2.4).
Incidence

Incidence
There is little research into what proportion of people develop acute stress reactions to severe stress. In a study of accident survi-vors, 14 per cent experienced a response pattern characterized by 4.6.1 acute stress reactions

SECTION 4  clinical syndromes of adult psychiatry 696
derealization, and a further 17 per cent exhibited strong anxiety or 
dysphoria.(16)
Estimates of the incidence of acute stress disorder range from 
about 14 per cent in motor vehicle accident survivors to 33 per cent in witnesses of a mass shooting.
(17) Given the variable procedures 
and assessment tools employed across studies, it is difﬁ  cult to 
determine whether the different rates of acute stress disorder detected are attributable to differences in method or in the type of trauma.
Data on comorbidity are sparse. Given the similarities between acute stress disorder and PTSD it is likely that the conditions found to be comorbid with PTSD, in particular depression and substance abuse, will be applicable to acute stress disorder (see Chapter 4.6.2).
Aetiology

Aetiology
Both psychological and biological theories have attempted to explain the symptoms of acute stress disorder. They overlap largely with theories of PTSD (see Chapter 4.6.2). Given that acute stress reaction describes a transient disturbance, there are no speciﬁ  c 
theories of acute stress reactions as deﬁ  ned in ICD-10.
Psychological theories
The psychological mechanism that has received the most attention 
in relation to acute stress disorder is dissociation, as reﬂ  ected in the 
DSM-IV criteria. It has been argued that dissociation minimizes the adverse emotional consequences of trauma by restricting awareness of the experience to avoid overwhelming fear and loss of control.
(13) Dissociation is thought to prevent recovery because it 
prevents the integration of the traumatic experience into existing schemas
(18) and it prevents the full activation of the trauma mem-
ory which is thought to be necessary for its modiﬁ  cation.(19) In line

ory which is thought to be necessary for its modiﬁ  cation.(19) In line 
with these hypotheses, dissociation during or immediately after a traumatic event predicts PTSD.
(20) In contrast, an alternate view 
posits that dissociation at the time of trauma may serve a protective function because it may limit the encoding of aversive experiences and this may assist adaptation.
(21) Consistent with this view, there 
is evidence that persisting dissociation (which is a form of cogni-tive avoidance) is more predictive of PTSD than dissociation that occurs at the time of trauma.
(22,23)
Psychological theories of acute stress disorder and PTSD focus

(22,23)
Psychological theories of acute stress disorder and PTSD focus 
on the personal meaning of the trauma and its consequences, and characteristics of the trauma memory. Several hypotheses about the problems in memory that are responsible for the characteristic re-experiencing symptoms (i.e. unwanted memories of aspects of the trauma that occur in response to a wide range of stimuli) have been suggested (see also Chapter 4.6.2). Foa and colleagues
(24,25)
suggested that PTSD is characterized by a pathological network in memory that is particularly large and easily triggered. It contains many stimulus propositions that are erroneously linked to danger, causing fear responses to harmless stimuli that are associated with the traumatic event in memory. Brewin et al.
(26) postulated that 
two different representations of the trauma are formed in memory. The ﬁ  rst, termed verbally accessible memory, contains the con-

scious recollection of the trauma. The second memory representa-tion, termed situationally accessible memory, comprises sensory, physiological, and motor aspects of the trauma in the form of codes that enable the re-experiencing of the original experience. Ehlers 
and Clark
(27) suggested three memory processes to explain that a

and Clark
(27) suggested three memory processes to explain that a 
wide range of stimuli can trigger vivid memories and strong emo-tional responses, which are experienced as if the traumatic event was happening at present. First, trauma memory is thought to be inadequately linked to its context in memory, which leads to poor inhibition of stimulus-driven retrieval. Two other basic memory processes, perceptual priming and associative learning, are thought to further enhance the chances of stimulus-driven retrieval of memories. Consistent with these psychological theories, there is evidence that chronic PTSD is predicted by impaired access to autobiographical memories
(28) and the perceived ‘nowness’ of 
trauma memories.(29) There is also evidence that maladaptive 
appraisals such as ‘I am inadequate’ , ‘My reactions since the trauma mean I am losing my mind’ , or ‘I have permanently changed for the worse’ in the acute phase after trauma exposure predict chronic PTSD .
(30,31)

(30,31)
Psychological models also concur that successful adaptation to 
trauma involves integration of corrective information, and any strategies that minimize this process will contribute to subsequent PTSD. Excessive use of such avoidant strategies (e.g. trying not to think about the trauma, efforts to push intrusive memories out of one’s mind, ruminating about how the trauma could have been avoided) prevent recovery.
(24–27)  There is preliminary empirical 
evidence supporting this hypothesis.(30–33)
Biological theories
Biological models have focused on fear conditioning and progres-sive neural sensitization in the weeks after trauma.
(34) Speciﬁ  cally,

(34) Speciﬁ  cally, 
when a traumatic event (unconditioned stimulus) occurs, people typically respond with fear (unconditioned response). It is argued that the strong fear elicited by the trauma will lead to strong asso-ciative conditioning between the fear and the stimuli surrounding the trauma. As reminders of the trauma occur (condi tioned stimuli),

people then respond with fear reactions (conditioned response). It has been hypothesized that extreme sympathetic arousal at the time of a traumatic event may result in the release of stress neuro-chemicals (including norepinephrine and epinephrine) into the cortex, mediating an overconsolidation of trauma memories. It is possible that sensitization occurs as a result of repetitive activation by trauma reminders and re-experiencing symptoms, elevating sensitivity of limbic networks, and that as time progresses these 
responses become increasingly conditioned to trauma-related 
stimuli.
(35) In support of these proposals, there is evidence that 
people who eventually develop PTSD display elevated resting heart rates in the initial week after trauma.
(36) There is also evidence that 
most people with acute stress disorder suffer panic attacks during the traumatic experience, and most of these people continue to suffer ongoing panic attacks in the subsequent month.
(37)

(37)
Whereas the ICD-10 criteria deﬁ  ne an acute stress reaction as a 
disorder that remits within a few days, DSM-IV conceptualizes acute stress disorder as a marker of those vulnerable to the devel-opment of PTSD. Evidence relating to these different assumptions was sparse at the time the diagnoses were established. One explicit goal of the acute stress disorder diagnosis is to identify people who

697
will develop PTSD. This goal is difﬁ  cult to achieve because most 
people who initially display acute stress reactions adapt in the following 3 months.
(38) Across 12 studies that have assessed the 
relationship between acute stress disorder and PTSD, most studies have found that whereas most people with acute stress disorder do develop PTSD, the acute stress disorder diagnosis does not capture the majority of people who develop PTSD.
(38) It appears that the 
requirement for dissociative symptoms in the acute phase to be present results in a failure to identify many people who are high risk for PTSD development. It is important to note that similar patterns have been noted in prospective studies of children after trauma.
(39–41) Across studies, people who have more severe symptoms 
of PTSD in the weeks following trauma have a poorer prognosis than those with less severe symptoms.
(42,43)
Predictors of acute stress disorder

(42,43)
Little is known about predictors of acute stress reactions. A history of psychiatric disorder, depressive and dissociative symptoms prior to the traumatic event, and previous trauma predict acute stress disorder.
(22,44,45)
Treatment
(a) Debrieﬁ  ng
Critical incident stress debrieﬁ  ng is a widely practised intervention 
that has the goal of promoting adaptation to traumatic events. Debrieﬁ  ng is generally conducted in a group within 24 to 72 h of 
the trauma. However, these parameters have been modiﬁ  ed to per-
mit more ﬂ  exible interventions. Mitchell
(46) proposes that debrief-
ing comprises seven phases:
1 an initial outline of the purpose and beneﬁ  ts of debrieﬁ  ng;
2 the fact phase, in which participants relate what happened to 
them;
3 a thought phase, in which participants relate their initial thoughts

them;
3 a thought phase, in which participants relate their initial thoughts 
after the critical incident;
4 a feeling phase, which requires participants to focus on the worst 
aspects of the incident and engage in their emotional reactions to the incident;
5 an assessment phase, in which participants are trained to note 
their physical, cognitive, emotional, and behavioural symptoms;
6 an education phase, which provides information about stress 
responses and ways to manage them;
7 the re-entry phase, in which the information given is summa-
rized and referral information offered.
These phases may take 1 to 5 h, and are usually coordinated by a 
trained mental health professional.
Anecdotal evidence and clinical reports attest to the efﬁ  cacy 
of debrieﬁ  ng. However, despite its widespread use, few controlled

of debrieﬁ  ng. However, despite its widespread use, few controlled 
trials have been conducted. These have mainly focused on single session individual debrieﬁ  ng. A Cochrane review of 15 randomized 
controlled studies of psychological debriefing
(47) found that 
although participants usually found the intervention useful, debrieﬁ  ng did not prevent the onset of PTSD nor reduce psychologi-
cal distress compared to control. The two studies with the longest follow-up actually found that the debrieﬁ  ng group had a worse long-term outcome than the control group.
(48–50) These results 
suggest that single session individual debrieﬁ  ng is not effective.(47)
In line with these results on individual debrieﬁ  ng, the ﬁ  rst 
two non-randomized controlled studies of the efﬁ  cacy of group 
debrieﬁ  ng found that the intervention had no beneﬁ  cial effects on

debrieﬁ  ng found that the intervention had no beneﬁ  cial effects on 
post-trauma symptoms.(51,52) One of the studies found negative 
effects of the intervention after 18 months.(52) A large trial of 
1050 soldiers on a peacekeeping mission found no differences on all outcomes between a full programme of critical incident stress debrieﬁ  ng, stress education, and no intervention.
(53)
(b) Cognitive behaviour therapy
Cognitive behavioural interventions are effective in treating PTSD 
(see Chapter 4.6.2). The results of randomized controlled studies of rape victims and road trafﬁ  c accident survivors suggest that a 
brief ﬁ  ve-session version of this treatment is effective in acute stress 
disorder and prevents the development of chronic post-trauma reactions.
(54–58)  Treatment involved the following:
1 education about trauma reactions;2 progressive muscle relaxation;3 prolonged exposure;

4 cognitive restructuring of fear-related beliefs;
5 graded in vivo  exposure.
Cognitive behaviour therapy was found to be superior to other 
psychological therapies such as non-directive therapy or relaxation in preventing chronic PTSD.
(59,60)
Psychopharmacological treatment
Little is known about which pharmacological interventions are effective in acute stress reactions/disorder. Preliminary studies report the utility of tricyclic antidepressants, but no or even harmful effects of benzodiazepines.
(59–61) Research on PTSD suggests 
that selective serotonin reuptake inhibitors are, to date, the best pharmacological treatment for persistent reactions to traumatic stress (see Chapter 4.6.2).
There is growing interest in pharmacological interventions in 
the acute phase following the trauma that may prevent the devel-opment of PTSD symptoms.

(62) A pilot study attempted to prevent 
PTSD by administering propranolol (a β-adrenergic blocker) with-
in 6 h of trauma exposure.(63) This approach is based on evidence 
that propranolol abolishes the epinephrine enhancement of fear conditioning.
(64) Although propranolol did not result in reduced 
PTSD relative to a placebo condition, patients receiving proprano-lol displayed less reactivity to trauma reminders 3 months later. This outcome accords with an uncontrolled study that found that propranolol administered immediately after trauma resulted in reduced PTSD 3 months later.
(65) These preliminary data suggest

(65) These preliminary data suggest 
that propranolol administration shortly after trauma exposure may limit fear conditioning that may contribute to subsequent PTSD development. Two other pilot studies found that high doses of hydrocortisol given to medical patients in an intensive care environment had a beneficial effect on subsequent PTSD symptoms.
(62,66)  One possible pathway of action is that cortisol 
contains strong epinephrine responses during stress, and may thus indirectly inﬂ  uence the strength of fear conditioning.
(62) However, 
these experimental studies are as yet too preliminary to suggest clinical application.
(60)4.6.1 acute stress reactions

SECTION 4  clinical syndromes of adult psychiatry 698
Information and self-help booklets
Several studies have evaluated the effectiveness of information or 
self-help booklets as early interventions after trauma. They consis-tently found that such interventions are ineffective and do not decrease the risk of chronic PTSD symptoms, although patients report that they ﬁ  nd the booklets helpful.
(67,68)
As acute stress reactions (ICD-10) are transient, and trials showed 
that early psychological debrieﬁ  ng is not effective in reducing 
future symptoms, psychological interventions that focus on recounting the traumatic event and ventilation of feelings are not indicated in the initial days after trauma exposure.
(59,60) Instead, 
clinicians should focus on ensuring trauma survivors’ safety and security, providing support and practical assistance, and encourag-ing them to actively use their social support.
(59,60) Although drug

(59,60) Although drug 
treatments are not recommended as a preventative intervention following traumatic exposure,
(60) clinicians may consider short-
term hypnotic medication or longer term use of antidepressants for the management of signiﬁ  cant sleep disturbance in the acute phase 
after trauma.
(59,61) Furthermore, patients may ﬁ  nd information 
about common reactions to trauma and their course, and practical advice about issues such as hospital procedures, police questioning, insurance claims, legal procedures, and media pressure to tell one’s story helpful. Clinicians should offer follow-up appointments and monitor trauma survivors for the development of PTSD.
(59)
An important clinical task is the early identiﬁ  cation of those 
trauma survivors who are likely to develop chronic and disabling post-trauma symptoms.
(47,59)  If symptoms persist for 2 weeks or

(47,59)  If symptoms persist for 2 weeks or 
longer, treatment may be indicated. However, patients with low symptom severity at 2 weeks have a good chance of recovering without intervention, and clinicians may want to initially monitor symptom progression for a month to determine whether the patient is recovering naturally.
(59) A number of short symptom 
screening questionnaires have been developed that may provide useful predictive information for this purpose in the future, but still await cross-validation in other samples.
(69)
For trauma survivors with more severe acute stress disorder 
symptoms, a course of cognitive behavioural treatment should be considered.
(59,60)  This form of intervention is typically not provid-

ed within 2 weeks of trauma exposure. If the patient is offered cognitive behavioural treatment, therapists need to be aware that avoidance is a hallmark symptom of acute stress disorder and may reduce the likelihood that an individual will attend treatment ses-sions regularly. Flexible treatment procedures (e.g. initial contacts by telephone, scheduling sessions around the patient’s preferences) and discussions about the ambivalence towards treatment may be helpful. Therapists need to be knowledgeable about the conditions surrounding the traumatic event and be sensitive to the particular socio-cultural background of the patient, which will affect the personal meaning of the event. Other forms of psychological treat-ment that do not address traumatic memories (such as relaxation or non-directive therapy) should not be routinely offered.
(59)

(59)
The lack of randomized controlled trials suggests that pharma-
cological treatment cannot be considered a front-line treatment for acute stress disorder,
(59,60) but research on PTSD suggests that 
selective serotonin reuptake inhibitors and other antidepressants may be helpful (see Chapter 4.6.2).Possibilities for prevention
Identifying highly symptomatic individuals with acute stress disorder and providing a cognitive behavioural intervention from 2 weeks post-trauma onwards may reduce the risk of chronic PTSD. Additional preventive methods have been explored that prepare individuals ‘at risk’ (e.g. emergency services and military personnel) for experiencing trauma so as to enhance their coping strategies and reduce the risk of them developing longer-term symptomatol-ogy. For those individuals at high risk of experiencing a trauma, providing them with training to remain calm, evaluate the situa-tion objectively,
(70) to not identify with victims, to utilize social

(70) to not identify with victims, to utilize social 
supports, and to express emotional reactions(71) have all been 
found to be associated with better coping after the trauma. However, evidence remains preliminary and it remains unclear whether they affect the risk of PTSD.
McNally, R.J., Bryant, R.A., and Ehlers, A. (2003). Does early psychological 
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National Institute of Clinical Excellence. (2005). Clinical guideline 26: post-
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National Center for Posttraumatic Stress Disorder. http://www.ncptsd.
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Australian Centre for Posttraumatic Mental Health. (2007). Australian

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stress disorder
Clinicians have long noted that traumatic events can lead to severe

Clinicians have long noted that traumatic events can lead to severe 
psychological disturbance. At the end of the nineteenth and the beginning of the twentieth centuries, railway disasters, the World Wars, and the Holocaust prompted systematic descriptions of the symptoms associated with traumatic stress reactions. These include the spontaneous re-experiencing of aspects of the traumatic events, startle responses, irritability, impairment in concentration and memory, disturbed sleep, distressing dreams, depression, phobias, guilt, psychic numbing, and multiple somatic symptoms. A variety of labels were used to describe these reactions including ‘fright neurosis’ , ‘combat/war neurosis’ , ‘shell shock’ , ‘survivor syndrome’ , and ‘nuclearism’ .
(1–3)
Whether the traumatic event can be considered a major cause of

(1–3)
Whether the traumatic event can be considered a major cause of 
these psychological symptoms, has been the subject of considerable debate. Charcot, Janet, Freud, and Breuer suggested that hysterical symptoms were caused by psychological trauma, but their views were not widely accepted. The dominant view was that a traumatic event in itself was not a sufﬁ  cient cause of post-trauma symptoms, 
and experts searched for other causes. Many suspected an organic cause. For example, damage to the spinal cord was suggested as the cause of the ‘railway spine syndrome’ , microsections of exploded bombs entering the brain as the cause of ‘shell shock’ , and starva-tion and brain damage as causes of the chronic psychological difﬁ culties of concentration camp survivors. Others doubted the 
validity of the symptom reports and suggested that malingering and compensation-seeking (‘compensation neurosis’) was the 
major cause in most cases. Finally, the psychological symptoms

major cause in most cases. Finally, the psychological symptoms 
were attributed to pre-existing psychological dysfunction. The predominant view was that reactions to traumatic events are tran-sient, and that therefore only people with unstable personalities, pre-existing neurotic conﬂ  icts, or mental illness would develop 
chronic symptoms.
(1–3)
It was the recognition of the long-standing psychological problems 
of many war veterans, especially Vietnam veterans, that changed this view and convinced clinicians and researchers that even people with sound personalities can develop clinically signiﬁ  cant psycho-
logical symptoms if they are exposed to horriﬁ  c stressors. This 
prompted the introduction of post-traumatic stress disorder (PTSD) as a diagnostic category in DSM-III.
(4) It was thus recognized

(4) It was thus recognized 
that traumatic events such as combat, rape, man-made, or natural disasters give rise to a characteristic pattern of psychological symp-toms. The diagnostic criteria speciﬁ  ed the experience of a traumatic 
event as a necessary condition for the diagnosis. ICD-10
(5) empha-
sized the causal role of traumatic stressors in producing psycho-logical dysfunction even more clearly, in that a speciﬁ  c group of 
disorders, ‘reaction to severe stress, and adjustment disorders’ , was created. These disorders are ‘thought to arise always as a direct consequence of the acute severe stress or continued trauma. The stressful event . . . is the primary and overriding causal factor, and the disorder would not have occurred without its impact’ .

701
What makes a stressor traumatic?
In everyday language, many upsetting situations are described 
as ‘traumatic’ , for example, divorce, loss of job, or failing anexamination. However, a ﬁ  eld study designed to establish what 
kinds of stressors lead to the characteristic symptoms of PTSD, 
showed that only 0.4 per cent of a community sample developed 
the characteristic symptoms of PTSD in response to such ‘lowmagnitude’ stressors.
(6) Thus, in diagnosing PTSD, it appeared
necessary to employ a strict definition of what constitutes atraumatic stressor.
Few people would contest that horriﬁ  c events such as rape or 
bombings are traumatic. In an attempt to capture the essence of these stressors, the authors of DSM-IIIR required a traumatic 
stressor to be ‘outside the range of usual human experience’ and 
that it ‘would be markedly distressing to almost anyone’ .
(7) However,

(7) However, 
epidemiological studies showed that stressors that can lead to PTSD are actually quite common, for example road trafﬁ  c accidents
(8) or 
sexual assault.(9) Thus, the DSM-IIIR deﬁ  nition appeared too 
restrictive.
ICD-10 uses a broader deﬁ  nition and characterizes traumatic 
stressors by their exceptional severity and the distress they would cause for the average person ‘a stressful event or situation . . . of an 
exceptionally threatening or catastrophic nature, which is likely 
to cause pervasive distress in almost anyone’ .
(5) Thus, the ICD-10 
diagnosis refers to a common sense understanding of which 
situations are likely to be extremely distressing.
In contrast, the authors of DSM-IV(10) attempted a speciﬁ  c 
deﬁ nition. On the basis of research ﬁ  ndings that threat to life or

deﬁ nition. On the basis of research ﬁ  ndings that threat to life or 
physical integrity during the event is one of the most consistent predictors of PTSD,
(11) DSM-IV requires that the person ‘experi-
enced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others’ . The authors of DSM-IV made a further important step, in that they moved away from a purely situational deﬁ  nition and included the person’s subjective 
response to the situation as an additional criterion, requiring that the ‘person’s response involved intense fear, helplessness, or horror’ (or disorganized or agitated behaviour in the case of children).
(10)

(10)
The latter criterion takes into account that there is a large inter-individual variability in the psychological response to the samesituation.
The stressor criterion of DSM-IV is still under debate. Recent 
research suggests that both components of the definition
may require extension. First, it may be necessary to includefurther possible emotional responses to traumatic stressors. There is accumulating evidence that emotional numbing duringtraumatic events is predictive of PTSD.
(12) Furthermore, it
has been established that perpetrators of violent crime some-times develop PTSD. Witnessing or participating in war-related crimes such as torturing or killing prisoners of war andcivilians and mutilation of corpses is more closely linked to PTSD in Vietnam veterans than the threat of death associated with combat.
(13) The psychological state of the perpetrators

(13) The psychological state of the perpetrators 
during the events that later lead to PTSD has not been studied in detail, but it isdoubtful that they would meet the currentDSM-IV definition. Feelings of shame or guilt that were experi-enced at the time or subsequently, may be predictive of PTSD in this group.
(14)Second, the emphasis on threat to life or physical integrity may 
omit important dimensions of subgroups of traumatic events. The threat to the perception of oneself as an autonomous human being may be a relevant dimension of traumatic events that involve inten-tional harm by other people.
(15) Mental defeat, the perceived loss of 
all autonomy, was related to PTSD in political prisoners and assault victims,
(15,16) independent of other indicators of trauma severity 
including threat to life and perceived helplessness.

The most characteristic symptoms of PTSD are the re-experiencing symptoms. Patients involuntarily re-experience aspects of the traumatic event in a very vivid and distressing way. This includes: ﬂ ashbacks in which the person acts or feels as if the event were 
recurring; nightmares; and intrusive images or other sensory impressions from the event. For example, a woman who was assaulted kept seeing the eyes of the perpetrator looking through the letterbox before he broke into her house, and a man involved in a severe car crash at night kept hearing the sound of the impact. Despite these vivid memory fragments, intentional recall of the event is often disorganized, and some patients have amnesia for parts of the event (see also Chapter 4.6.3).
Reminders of the trauma arouse intense distress and/or physio-

logical reactions and are consequently avoided, including conversa-
tions about the event. Patients try to push memories of the event 
out of their mind and avoid thinking about the event in detail, particularly about its worst moments. On the other hand, many ruminate excessively about questions that prevent them from coming to terms with the event, for example about why the event happened to them, about how it could have been prevented, or about how they could take revenge.
The patients’ emotional state ranges from intense fear, anger, 
sadness, guilt, or shame to emotional numbness. They often 
describe feeling detached from other people and give up previously 
signiﬁ  cant activities. Various symptoms of hyperarousal include 
hypervigilance, exaggerated startle responses, irritability, difﬁ  culty 
concentrating, and sleep problems.
ICD-10(5) classiﬁ  es PTSD (F43.1) among the reactions to severe

ICD-10(5) classiﬁ  es PTSD (F43.1) among the reactions to severe 
stress and adjustment disorders (F43) that are primarily caused by stressful events. DSM-IV
(10) classiﬁ  es PTSD (309.81) among the 
anxiety disorders because symptom patterns, psychophysiological responses, family studies, and the efﬁ  cacy of exposure treatment 
and serotonergic drugs suggested a relationship with other anxiety disorders. However, some of the symptoms would also suggest a relationship with dissociative disorders (e.g. amnesia) or depression (e.g. loss of interest).
(17,18)
Diagnostic criteria in ICD-10 and DSM-IV
Table 4.6.2.1 compares the diagnostic criteria of ICD-10 and DSM-IV .
(10) ICD-10 research diagnostic criteria,(19) as well as diag-
nostic guidelines,(5) are included. The diagnostic systems agree

nostic guidelines,(5) are included. The diagnostic systems agree 
on the core symptoms of PTSD (re-experiencing, avoidance, emotional numbing, and hyperarousal), but differ in the weight assigned to them. DSM-IV criteria are stricter.4.6.2 post-traumatic stress disorder

SECTION 4  clinical syndromes of adult psychiatry 702
Table 4.6.2.1  Diagnostic criteria for PTSD in ICD-10 and DSM-IV
ICD-10 diagnostic guidelines ICD-10 research diagnostic criteria DSM-IV criteria
1  Event or situation of exceptionally 
threatening or catastrophic nature(a) 1  Event or situation of exceptionally 
threatening or catastrophic nature(a) 1  The person experienced, witnessed,or was confronted with an 
event or events that involved actual or threatened death or 
serious injury, or a threat to the physical integrity of self or others
2  Likely to cause pervasive distress in 
almost anyone  2  Likely to cause pervasive distress in 
almost anyone  2  The person’s response involved intense fear, helplessness, or 
horror (or disorganized or agitated behaviour in children)
Symptom criteria
Necessary symptom Necessary symptoms Necessary  symptoms
1  Repetitive intrusive recollection or 
re-enactment of the event in memories,

re-enactment of the event in memories, 
daytime imagery, or dreams(b)  Persistent remembering or ‘reliving’ of 
the stressor in intrusive ‘ﬂ  ashbacks’, vivid 
memories, or recurring dreams, and in experiencing distress when exposed to 
circumstances resembling or associated 
with the stressor(b)  The traumatic event is persistently re-experienced in one (or more) 
of the following ways
1  Recurrent and intrusive distressing recollections of the event, 
including images, thoughts, or perceptions (or repetitive play in which the themes or aspects of the trauma are expressed in 
children)
Other typical symptoms2  Sense of ‘numbness’ and emotional 
blunting, detachment from others, unresponsiveness to surroundings, 
anhedonia
3  Avoidance of activities and situations 
reminiscent of trauma
Common symptoms
4  Autonomic hyperarousal with insomnia

anhedonia
5  Anxiety and depression(c)  Actual or preferred avoidance of 
circumstances resembling or associated with the stressor which was not present 
before exposure to the stressor
(d) 1  Inability to recall, either partially or 
completely, some important aspects 
or the period of exposure to the 
stressor
or2  Recurrent distressing dreams of the event (or frightening dreams 
without recognizable content in children)
3  Acting or feeling as if the traumatic event were recurring 
(or trauma-speciﬁ  c re-enactment in children)
4  Intense psychological distress at exposure to internal or external 
cues that symbolize or resemble an aspect of the traumatic event
5  Physiological reactivity at exposure to internal or external cues that 
symbolize or resemble an aspect of the traumatic event

Rare symptoms
6  Dramatic acute bursts of fear, panic, or 
aggression triggered by reminders2  Persistent symptoms of increased 
psychological sensitivity and arousal 
(not present before exposure to stressor), 
shown by any two of the following
(a) Difﬁ  culty in falling or staying asleep
(b) Irritability or outbursts of anger(c) Difﬁ  culty in concentrating(d) Hypervigilance(e) Exaggerated startle response(c)  Persistent avoidance of stimuli associated with the trauma and 
numbing of general responsiveness (not present before trauma), as indicated by three (or more) of the following
1  Efforts to avoid thoughts, feelings, or conversations associated with 
the trauma
2  Efforts to avoid activities, places, or people that arouse recollections 
of the trauma

the trauma
3 Inability to recall an important aspect of the trauma
4 Markedly diminished interest or participation in signiﬁ  cant activities
5 Feeling of detachment or estrangement from others
6 Restricted range of affect7 Sense of foreshortened future
(d)  Persistent symptoms of increased arousal (not present before the 
trauma), as indicated by two (or more) of the following
1 Difﬁ  culty falling or staying asleep
2 Irritability or outbursts of anger3 Difﬁ  culty concentrating4 Hypervigilance5 Exaggerated startle response
Time frame
Symptoms should usually arise within 
 6 months of the traumatic eventSymptoms should usually arise within 
 6 months of the traumatic eventSymptoms present for at least 1 month
Disability criterion
N/A N/A The disturbance causes clinically signiﬁ  cant distress or impairment in

6 months of the traumatic eventSymptoms present for at least 1 month
N/A N/A The disturbance causes clinically signiﬁ  cant distress or impairment in 
 social, occupational, or other important areas of functioning
(continued)

703
Table 4.6.2.1  (Continued) Diagnostic criteria for PTSD in ICD-10 and DSM-IV
Differential diagnoses
1  Acute stress reaction F43.0 (immediate 
reaction in the ﬁ  rst 3 days after event)
2  Enduring personality change after a 
catastrophic experience F62.0 (present 
for at least 2 years, only after extreme and prolonged stress)
3  Adjustment disorder (less severe stressor 
or different symptom pattern)
4  Other anxiety or depressive disorders 
(absence of traumatic stressor or 
symptoms precedes stressor)Same as ICD-10 diagnostic guidelines 1 Acute stress disorder (duration of up to 4 weeks)
2  Adjustment disorder (less severe stressor or different symptom 
pattern)
3  Mood disorder or other anxiety disorder (symptoms of avoidance, 
numbing, or hyperarousal present before exposure to the stressor)
4  Other disorders with intrusive thoughts or perceptual disturbances

4  Other disorders with intrusive thoughts or perceptual disturbances 
(e.g. obsessive–compulsive disorder, schizophrenia, other psychotic 
disorders, substance-induced disorders)
X DSM-IV puts a stronger emphasis on the avoidance/numbing 
cluster of symptoms by requiring a minimum of three of these symptoms.
X DSM-IV states two additional criteria that are not included in 
ICD-10, namely a minimum symptom duration of 1 month and signiﬁ  cant distress or impaired functioning.
A large-scale study
(20) found a prevalence of ICD-10 PTSD of 6.9 
per cent, and a prevalence of DSM-IV PTSD of 3 per cent.
Differential diagnoses are summarized in Table 4.6.2.1. Distinguishing features include the following:
X the type of stressor (adjustment disorders, enduring personality 
change)
X the symptom pattern (adjustment disorders, enduring personal-
ity change)

change)
X the duration of the symptoms (acute stress disorder, acute stress 
reaction)
X the question of whether the avoidance, numbing, and hyper-
arousal symptoms were present before the traumatic event occurred (other anxiety or depressive disorders)
X the nature of the intrusive cognitions and perceptual disturbances 
(obsessive-compulsive disorder, psychotic symptoms, substance-induced symptoms).
Prolonged repeated trauma, such as captivity or repeated 
childhood sexual abuse, may lead to a more complex pattern of symptoms, ‘complex PTSD’ , that is characterized by somatization, dissociation, affect dysregulation, poor impulse control, self-destructive behaviour, and pathological patterns of relation-ships.
(21) It was debated whether to include a category ‘disorders of 
extreme stress not otherwise speciﬁ  ed’ (DESNOS) into DSM-IV to

extreme stress not otherwise speciﬁ  ed’ (DESNOS) into DSM-IV to 
accommodate these cases, but the decision was not to include it.(17)
In ICD-10, the diagnosis ‘enduring personality changes after cata-strophic experience’ covers such long-standing consequences of enduring trauma.Furthermore, it is currently being debated whether an additional 
diagnostic category ‘traumatic grief’ should be included into the psychiatric classiﬁ  cation systems.
(22)
Ongoing research on symptom criteria
Some research has questioned the symptom clusters of DSM-IV . 
In particular, it may be preferable to assess the emotional numbing symptoms separately from the avoidance symptoms, because these symptoms do not load on the same factor in factor analyses and may have different underlying mechanisms. Furthermore, it may be preferable to include severity criteria for the symptoms rather than relying on counting the presence of symptoms.
(23)

(23)
Several semi-structured interviews assess the DSM-IV criteria for PTSD. The most commonly used diagnostic interviews are the Structured Clinical Interview for DSM-IV (SCID)
(24) and the 
Clinician Administered PTSD scale (CAPS).(25)
The most widely used self-report measure of PTSD symptoms 
used to be the Impact of Event scale.(26) The original scale contained 
two scales, an intrusion and an avoidance scale. It has been expanded to include an additional hyperarousal scale (IES-R).
(27)
The IES-R does not cover all the symptoms of PTSD speciﬁ  ed in 
DSM-IV . This is why new measures that are modelled on the DSM-IV criteria are now commonly used in research studies, for example the Post-traumatic Stress Diagnostic scale (PDS)
(28) or the 
PTSD Checklist (PCL).(29)

(28) or the 
The available epidemiological data so far stem mainly from large-scale studies in industrialized societies such as the United States or Australia. It remains to be investigated whether these data replicate in other countries. One has to bear in mind that the society and natural environment set conditions for exposure to traumatic events. For example, in the last decades, people in developing countries have had a much greater exposure to war and natural disasters than people in industrialized western societies.
(30)4.6.2 post-traumatic stress disorder

SECTION 4  clinical syndromes of adult psychiatry 704
How common are traumatic events in the population?
Traumatic events are common. In a large representative United States’ 
sample, Kessler et al .(31) found that 60.7 per cent of the men and 
51.2 per cent of the women had experienced at least one traumatic event meeting DSM-IIIR criteria in their lifetime. The most common types of trauma were witnessing someone being killed or severely injured, accidents, and being involved in a ﬁ  re, ﬂ  ood, or natural 
disaster. Using DSM-IV criteria, Stein et al .
(32) found a lifetime 
exposure to serious traumatic events of 81.3 per cent for men, and 74.2 per cent for women. Sudden death of a loved person was one of the most frequent traumatic stressors (DSM-IV criteria).
(33)
What types of trauma are associated with high 
PTSD rates?
PTSD rates depend on the type of traumatic event. Rape was asso-

(33)
ciated with the highest PTSD rates in several studies. For example, 65 per cent of the men and 46 per cent of the women who had been raped met PTSD criteria in the Kessler et al.
(31) study. Other 
traumatic events associated with high PTSD rates included combat exposure, childhood neglect and physical abuse, sexual molesta-tion; and for women only, physical attack and being threatened with a weapon, kidnapped, or held hostage. Accidents, witnessing death or injury, and ﬁ  re or natural disasters were associated with 
relatively low-lifetime PTSD rates of less than 10 per cent.
(31) Other 
research has shown high PTSD rates for torture victims,(34) survi-
vors of the Holocaust,(35) and prisoners of war.(36) The emphasis

(31) Other 
vors of the Holocaust,(35) and prisoners of war.(36) The emphasis 
in DSM-IV on threat to life or physical integrity has led to increas-ing awareness that medical illness and treatment (e.g. waking up during anaesthesia) can lead to PTSD.
(37)
What proportion of people develop PTSD in response 
to a traumatic stressor?
Kessler et al.(31) found that the risk of developing PTSD after a trau-
matic event is 8.1 per cent for men, and 20.4 per cent for women. For young urban populations, higher risks have been reported; Breslau et al. found an overall risk of 23.6 per cent
(38); 13 per cent for men 
and 30.2 per cent for women.(39)
The ﬁ  gures reported in these studies may be inﬂ  uenced by 
two types of biases that have opposite effects on probabilityestimates. First, Breslau et al .
(33) have pointed out that previous

(33) have pointed out that previous 
studies overestimated the PTSD-risk imposed by traumatic events because participants reported on the worst trauma that they had experienced. When assessment focused on the symptoms induced by a traumatic event that was randomly selected from the ones that a person had experienced, the conditional risk of PTSDfollowing exposure to trauma was found to be 9.2 per cent, using DSM-IV criteria.
Second, the retrospective methodology used in the epidemio-
logical studies may have led to underestimation of PTSD rates due to selective recall. For example, the prevalence of PTSD 3 months after road trafﬁ  c accidents was found to be around 20 per cent in 
prospective longitudinal studies,
(40,41) whereas the retrospective 
studies found prevalences below 10 per cent.

How prevalent is PTSD in the population?
Kessler et al .(31) estimated that the lifetime prevalence of PTSD
 is 7.8 per cent, using DSM-IIIR criteria. Women had a higherprevalence than men (10.4 versus 5.0 per cent). This was due to 
both a greater exposure to high-impact trauma (rape, sexual moles-tation, childhood neglect, and childhood physical abuse) and a greater likelihood of developing PTSD when exposed to a traumat-ic event. Other studies using DSM-IIIR criteria have yieldedsimilarly high prevalence rates.
(9,39) Estimates for the 12-month 
prevalence range between 1.3 per cent in an Australian study(42) and 
3.6 per cent in an US study.(43) A study using DSM-IV criteria and 
found a past-mo nth PTSD prevalence of 2.7 per cent for women 
and 1.2 per cent for men.(32)
Earlier studies using DSM-III criteria had reported lower lifetime

Earlier studies using DSM-III criteria had reported lower lifetime 
prevalences of about 1 per cent. Besides differences in procedures and sampling methods, the low PTSD prevalence in these earlier studies may be due to the use of an interview schedule with low sensitivity in detecting PTSD.
(44) In particular, the early interviews 
asked global questions about the occurrence of traumatic events and lacked the repeated probing for speciﬁ  c events or event catego-
ries that seems to be necessary in eliciting relevant experiences.
Partial PTSD
Several studies have found substantial levels of distress and disability for traumatized people who met some, but not all, of the PTSD criteria speciﬁ  ed in DSM-IV .
(32) These people may be at greater 
risk of developing the full PTSD syndrome than people with fewer symptoms.
(40,41)
Comorbidity of PTSD with other disorders 
and symptoms

(40,41)
PTSD shows a substantial comorbidity with affective disorders, 
other anxiety disorders, substance-use disorders, and somatization. In the study by Kessler et al .,
(31) 88.3 per cent of the men and
78.1 per cent of the women with PTSD had comorbid psychiatric diagnoses. Studies of veterans with PTSD have also indicated an enhanced level of problems in family and marital adjustment and violent behaviour,
(45) and heavy smoking.(46) Furthermore, reports of 
poor health and increased rates of various diseases, in particular infec-tious and nervous system diseases, are associated with PTSD.
(47)
Is PTSD primary or secondary to the comorbid diagnoses? There 
is, as yet, little research into this question. The retrospective accounts obtained by Kessler et al .
(31) suggested that PTSD was

(31) suggested that PTSD was 
primary to comorbid affective or substance-use disorders in the majority of cases, and PTSD was primary to comorbid anxiety dis-orders in about half of the cases. Similarly, Breslau et al.
(39) found 
that PTSD increased the risks for ﬁ  rst-onset major depression and 
alcohol-use disorder. Conversely, pre-existing major depression also increased vulnerability to the PTSD-inducing effects of trau-matic events and risk for exposure to traumatic events. A prospec-tive study conﬁ  rmed that PTSD increased the risk of subsequent 
pain, conversion symptoms, and somatization symptoms.
(48)
Most of the comorbidity research has concentrated on the nature

(48)
Most of the comorbidity research has concentrated on the nature 
of the relationship between PTSD and alcohol or drug abuse. The majority of studies found that PTSD precedes the development of alcohol-abuse problems. There are probably several mechanisms for this relationship. In the short-term, alcohol is used to self-medicate the symptoms of PTSD, but paradoxically intoxication and withdrawal symptoms may intensify the symptoms in the long-term.
(49)

705
Summary of main ﬁ  ndings from 
epidemiological studies
X The majority of people will experience at least one traumatic 
event in their lifetime.
X In assessing PTSD history, interviewers should probe for speciﬁ  c 
events.
X Assault, in particular sexual assault, and combat have a higher 
impact than accidents and disasters.(31,32)
X If the frequency and impact of traumatic events are considered 
together, sudden unexpected death of a loved one(33) and road 
trafﬁ c accidents(8) can be considered important causes of PTSD 
in western industrialized societies.
X Men tend to experience more traumatic events than women, but 
women experience higher impact events.(31,32)
X Women are at least twice as likely as men to develop PTSD in 
response to a traumatic event. This enhanced risk is not explained by differences in the type of traumatic event. The estimated life-time prevalence for women is approximately 10 to 12 per cent, and for men 5 to 6 per cent.
(9,31,38,39)

X Comorbid depression and substance-use disorders appear to be 
secondary to PTSD in the majority of cases.
Aetiology
There is no single accepted theory of PTSD. Theoretical explana-tions have focused on psychological and biological mechanisms that are not mutually exclusive.
Psychological processes
(a) Fear conditioning
Mowrer’s two-factor conditioning theory of phobias has been applied to PTSD.
(50–52)  It is suggested that through classical

(50–52)  It is suggested that through classical 
(Pavlovian) conditioning, stimuli that were present at the time of the trauma (unconditioned stimulus) become associated with fear and arousal responses. Subsequently, the conditioned stimuli trig-ger similar (conditioned) responses when presented on their own. Through stimulus generalization and higher-order conditioning, a wide variety of stimuli become triggers of distress in the aftermath of trauma. Quite naturally, the person will try to avoid the condi-tioned stimuli and the associated distress. The avoidance behaviour is negatively reinforced (operant or instrumental conditioning) because it leads to a reduction in psychological and physical dis-comfort. In the long-term, however, avoidance prevents extinction of the conditioned fear responses to reminders of the traumatic event, and thus maintains the problem.

(b)  Personal meanings of the traumatic event 
and its aftermath
The persistence of PTSD symptoms has been explained by indi-
vidual differences in the appraisal of the traumatic event: that is to say, in what personal meaning it has for them.
(53–55)  Some people 
are able to see the trauma as a time-limited terrible experience that does not necessarily have negative global implications for their view of themselves, the world or the future. These people are likely to recover quickly. Individuals with persistent PTSD are character-ized by excessively  negative appraisals of the event that go beyond what everyone would ﬁ  nd horriﬁ  c about the event. The nature of 
predominant emotional responses in PTSD depends on the par-ticular appraisals; for example, appraisals concerning danger lead

predominant emotional responses in PTSD depends on the par-ticular appraisals; for example, appraisals concerning danger lead 
to fear (‘Nowhere is safe’), appraisals concerning others violating personal rules lead to anger (‘Others have not treated me fairly’), appraisals concerning responsibility for the traumatic event lead 
to guilt or shame (‘It was my fault’ , ‘I did something despicable’), and appraisals concerning loss lead to sadness (‘My life will never be the same again’).
(55) Such appraisals distinguish between trau-
matized individuals with and without PTSD, and predict chronic PTSD.
(16,56)
Negative appraisals involved in maintaining PTSD do not only 
concern the traumatic event itself, but also its sequelae such as the initial PTSD symptoms or responses of other people in the after-math of the traumatic event.
(55,57,58)  In line with this hypothesis,

(55,57,58)  In line with this hypothesis, 
negative interpretations of intrusive recollections (e.g. ‘I am going mad’) after road trafﬁ  c accidents were one of the most important 
predictors of PTSD at 1 year after the event.
(41) Perceived negative 
responses from other people in the aftermath of trauma predicted PTSD in studies of assault and torture victims.
(15,16)
(c) Nature of trauma memories
What exactly distinguishes trauma memories from other memories and what explains the distressing re-experiencing symptoms in PTSD is still under debate.
(59,60) Phenomenological observations 
show that although a wide range of stimuli can trigger unwanted intrusive memories of parts of the traumatic event, people with 
PTSD show relatively poor intentional recall of details such as the order of events and their recall appears disjointed.
(60) Several theo-
ries have been put forward to explain re-experiencing symptoms. Foa and colleagues
(53,58) explain re-experiencing as spreading

(53,58) explain re-experiencing as spreading 
activation in a pathological network in memory. This network is thought to be particularly large and easily triggered. It contains many stimulus propositions that are erroneously linked to danger, causing fear responses to harmless stimuli associated with the trau-matic event in memory. In addition, the person’s reactions during the trauma are linked to the belief that the self is incompetent. Activation of components of the trauma memory (for instance, by confrontation to a reminder, by similar bodily sensations, or by thinking about the event) will activate the whole network, including the emotional responses that the person had during the traumatic event.
Brewin and colleagues
(61) have proposed that the symptoms of 
PTSD can only be explained if one assumes several levels of repre-

sentation of the traumatic event, namely a verbally accessible 
memory and a memory that is triggered by situation-speciﬁ  c cues. 
PTSD is thought to be characterized by easily accessible situation-ally speciﬁ  c memories that lead to re-experiencing symptoms.
Ehlers and Clark 
(55) suggested that re-experiencing results from 
three memory processes, namely, (i) poor inhibition of stimulus-
driven retrieval of parts of the trauma memory (re-experiencing) 
due to insufﬁ  cient elaboration of the trauma memory (insufﬁ  cient 
links to other information that would give the worst moments of the trauma a context such as ‘I survived the event’ or ‘I complied 
with the requests of the perpetrator because he had threatened me 
with a knife’), (ii) strong perceptual priming (low perceptual

with a knife’), (ii) strong perceptual priming (low perceptual 
threshold for stimuli with similar sensory characteristics as those present during the trauma), and (iii) strong associations among stimuli present at the time of the event (e.g. footsteps behind me 4.6.2 post-traumatic stress disorder

SECTION 4  clinical syndromes of adult psychiatry 706
associated with feeling knife in my back) and between stimuli 
and emotional responses (e.g. pressure on back associated with fear of death).
(d) Behaviours that maintain PTSD symptoms
Whereas many people will recover from initial PTSD symptoms, some do not get better. This has led researchers to specify possible maintaining behaviours. These include avoidance of reminders, suppression of thoughts and memories connected to the event, rumination, safety behaviours, dissociation, and the use of alcohol or drugs.
(57) Ehlers and Clark(55) suggested that these behaviours

(57) Ehlers and Clark(55) suggested that these behaviours 
and cognitive strategies maintain PTSD in three ways. First, some behaviours directly lead to increases in symptoms; for example, thought suppression leads to paradoxical increases in intrusion frequency. Second, other behaviours prevent changes in the prob-lematic appraisals; for example, constantly checking one’s rear mir-ror (a safety behaviour) after a car accident prevents change in the appraisal that another accident will happen if one does not check the mirror. Third, other behaviours prevent elaboration of the trauma memory and its link to other experiences. For example, avoiding thinking about the event may prevent people from incor-porating the fact that they did not die into the worst moments of the trauma memory, and they thus continue to re-experience the fear of dying they originally experienced during the event. 
Several studies have found that avoidance, safety behaviours,

Several studies have found that avoidance, safety behaviours, 
thought suppression, and rumination predict maintenance of PTSD.
(16,41)
Some of the cognitive processes that maintain PTSD symptoms 
are not intentional. Patients with PTSD have an unintentional attentional bias to stimuli that are reminiscent of the traumatic event.
(6) Involuntary selective attention to reminders may be one of 
the reasons why these patients have frequent re-experiencingsymptoms. Rumination is often described by the patient as unintentional. In particular, patients have problems stopping ruminating once they have started. Rumination may represent a cognitive habit that started as an intentional strategy employed to solve problems and that became more automatic with time.
Biological processes
A number of biological factors have been linked to PTSD symptoms. They have the effect that they make people with PTSD hyper-responsive to stressful stimuli, especially stimuli that are reminis-cent of the trauma.

(62)
(a) Chronic stress reaction
Patients with PTSD show several abnormalities that are consistent with a chronic stress reaction or an enhanced reactivity to minor stressors. There is evidence for an enhanced secretion of adrenaline (epinephrine) and noradrenaline (norepinephrine) to stress.
(63)
In psychophysiological studies, patients with PTSD showed enhanced startle responses and higher baseline heart rates and blood pressure than traumatized controls without PTSD. However, these responses may, in part, reﬂ  ect anticipatory anxiety related to 
the expectation of trauma cues. Patients with PTSD exhibit greater physiological reactivity to trauma cues (e.g. sounds, pictures, or script-driven imagery) than control subjects without PTSD.
(6)
(b) Hypothalamic-pituitary-adrenal axis abnormalities
Patients with PTSD show a different pattern of hypothalamic-pituitary-adrenal response than patients with major depression.

(6)
(63)Like depressed patients, patients with PTSD hypersecrete corticotrophin-releasing factor (CRF). However, they show lower
levels of cortisol compared to normal controls, traumatized individuals without current PTSD and depressed patients. When given a low dose of dexamethasone, PTSD patients exhibit hyper-
suppression of cortisol. Some, but not all ﬁ  ndings, suggest that 
the hypothalamic-pituitary-adrenal axis in PTSD may character-ized by enhanced negative feedback.
(64) Overall, the hypothalamic-
pituitary-adrenal axis in PTSD appears to be set to produce large responses to further stressors.
(c) Hypothalamic-pituitary-thyroid axis
Studies suggest increased hypothalamic-pituitary-thyroid axis activity in PTSD.
(63) Patients with PTSD showed increased levels of

(63) Patients with PTSD showed increased levels of 
thyroid hormones, and an exaggerated thyrotropin-stimulating hormone (TSH) response to the standard TSH stimulation test.
(d) Neuroendocrinological abnormalities
Several neurotransmitter systems appear to be dysregulated in PTSD.
(63,65) Research suggests exaggerated noradrenergic activity 
in PTSD in response to stressors.(65) People with PTSD have fewer 
plaletet α2-adrenergic receptors, which has been interpreted as a 
response to chronic elevation of circulating catecholamines. Y ohimbine (which blocks α
2-receptors) provokes ﬂ  ashbacks and 
panic attacks in a substantial subgroup of PTSD patients.(65)
There is also evidence for the involvement of the serotonergic 
system in PTSD.(63,65) Findings suggest decreased serotonin activity,

system in PTSD.(63,65) Findings suggest decreased serotonin activity, 
including decreased serum concentrations, decreased sensitivity of platelet serotonin uptake sites, and blunted prolactin response to d-fenﬂ  uramine (indicative of central serotonin hypo-activity). 
Serotonin-reuptake inhibitors have therapeutic effects in PTSD.
Endogenous opiates have been suspected to mediate the symp-
toms of emotional numbing and amnesia. In the animal model, uncontrollable stress leads to the secretion of endogenous opiates that induce analgesia. There is some evidence for decrease d base line
levels, but increased post-stimulation levels of ß-endorphin.
(63)
The dopaminergic and γ-aminobutyric acid (GABA) systems 
have also been implicated in PTSD, but the evidence for these hypotheses is sparse at this stage.
(63)
(e) Neuroimaging

(63)
(63)
Structural magnetic resonance imaging studies tend to show a 
reduced hippocampal volume in adults with PTSD, in particular in 
those with severe and very chronic PTSD, but not in children.(66)
Disturbances of hippocampal function may lead to deﬁ  cits in 
explicit memory and the appreciation of safe contexts. This line of research was prompted by animal studies showing that high levels of cortisol seen during stress are associated with damage to the hippocampus.
(67) However, there is evidence from a study of 
monozygotic twins that the hippocampal volume of the unexposed

twins correlated with the PTSD severity of the exposed twins. Thus, small hippocampal volume may be a vulnerability factor for PTSD, an effect of severe or chronic stress, or both. Preliminary evidence suggests that successful long-term treatment with paroxetine increases hippocampal volume in patients with PTSD.
(67)
Functional neuroimaging studies have found differences between 
people with and without PTSD in neurocircuits that are involved in 
fear conditioning (amygdalae, medial prefrontal cortex, hippocam-pus). When exposed to trauma reminders or other anxiety cues,
(68)
people with PTSD tend to show heightened responsivity of the

707
amygdala and diminished responsivity in the medial prefrontal 
cortex. The latter plays a role in extinguishing fear reactions, as ani-mal studies established that conditioned fear responses could only be extinguished if the cortex was intact.
(69) Recent studies suggest 
different patterns of responses to trauma reminders for people with PTSD who show high arousal to trauma reminders (involving mainly the anterior cingulate, medial prefrontal cortex, and thala-mus) versus those with dissociative reactions (involving mainly the parietal, occipital, and temporal cortex).
(70)
(f) Animal models of PTSD
There are biological and psychological parallels between the animal model of inescapable shock and exposure to a traumatic event. The uncontrollability of an aversive event seems to make it particularly traumatic.
(71) Inescapable shock leads to changes in the noradren-
ergic system, the HPA axis, and endogenous opiates that parallel ﬁ ndings in PTSD patients.
(51)

(51)
However, these effects are usually only observed after repeated 
exposure to inescapable shock, whereas one traumatic event can be sufﬁ cient in inducing PTSD. This is why some authors have sug-
gested that the animal model of kindling or behavioural sensitiza-tion is more appropriate in explaining PTSD. Kindling refers to a process whereby intermittent subconvulsive electrical stimulation of the limbic system eventually has the effect that the animal will respond with a seizure to a stimulus that previously was subthresh-old. Post et al.
(72) have suggested that the repeated re-experiencing 
of the traumatic event may constitute a kindling process, to the effect that PTSD symptoms become more easily triggered with time. Similarly, previous exposure to stressors may sensitize people to respond with PTSD symptoms to a traumatic event.

Animal models suggest that the massive secretion of neurohor-
mones at the time of the trauma, in particular noradrenaline and vasopressin, leads to overconsolidation (long-term potentiation) of the trauma memory. This would have the effect that the condi-tioned fear responses are particularly difﬁ  cult to extinguish and 
that stimuli that resemble those present during trauma are particu-larly likely to trigger intrusive memories, distress, and/or the corresponding physiological responses.
(62)
(g) Genetic factors
Twin studies have found a higher concordance of PTSD among monozygotic than dizygotic twins. There is also an increased prevalence of psychiatric disorders, especially anxiety disorders, affective disorders, sociopathy, and/or substance abuse, among family members of people with PTSD.
(73) A study found a higher 
proportion of the 5-HTTLPR s/s genotype in PTSD compared to controls.
(74)

(74)
For the vast majority of PTSD cases, symptoms begin immediately after the traumatic event. Delayed onset is found in a minority (11 per cent or less) of the cases.
(6)
Prospective longitudinal studies suggest that a large proportion 
of people who initially develop PTSD after trauma will recover on their own. However, between one-third and 50 per cent of those who develop PTSD after a traumatic event will not recover for many years.
(31,75) Long-term outcome depends on initial symptom 
severity and the experience of further traumatic events. People with high initial PTSD severity are more likely to remain symptomatic 
at follow-up than those with low initial symptom severity.(41,75)
Factors that inﬂ  uence the risk of developing PTSD
Meta-analyses(11,76)  have identiﬁ  ed several reliable predictors of

Meta-analyses(11,76)  have identiﬁ  ed several reliable predictors of 
PTSD. The results are summarized in Table 4.6.2.2. Overall, peri-traumatic factors such as perceived life threat and dissociation during the trauma and post-trauma factors such as low social sup-port appear more predictive of PTSD than pre-trauma variables.
(a) Demographic and pre-trauma variables
Women have consistently shown to have a greater risk of developing PTSD than men, but the mechanisms remain unclear.
(11,31,67,76,77) Similarly, it is as yet unclear why people with 
lower intelligence or education,(76) people with lower socioeco-
nomic status,(76) and people from ethnic minorities(78) have an 
elevated PTSD risk. Other risk factors include previous trauma, childhood adversity, a personal or family history of anxiety or depression,
(76) and neuroticism.(38)
(b) Stressor variables

PTSD risk depends on the severity of the stressor. Prolonged and repeated trauma, exposure to the grotesque aftermath of violence, events that involve intentional harm by another person and abusive violence, and events that involve harm to children are particularly likely to lead to PTSD.
(79,80)
Injury severity is only a weak predictor of PTSD. Long-term 
health problems and loss of function may play a greater role in maintaining PTSD.
(41,79) There are some reports that unconscious-
ness during a traumatic event may decrease the risk of PTSD,(81)
Table 4.6.2.2  Risk factors for post-traumatic stress disorder
Weighted average effect size r
Demographic variables
Female sex 0.13(76)
Race (minority status) 0.05(76)
Younger age 0.06(76)
Low socio-economic status 0.14(76)

Cognitive abilityLow education 0.10
(76)
Low intelligence 0.18(76)
Psychiatric and trauma historyPsychiatric history 0.11
(76)–0.17(11)
Family psychiatric history 0.13(76)–0.17(11)
Prior trauma 0.12(76)–0.17(11)
Childhood abuse 0.14(76)
Other adverse childhood 0.19(76)
Peri-traumatic factorsTrauma severity 0.23
(76)
Perceived life threat 0.26(11)
Peri-traumatic emotions 0.26(11)
Peri-traumatic dissociation 0.35(11)
Post-trauma factorsLow social support 0.28
(11)–0.40(76)
Further life stress 0.32(76)
(Modiﬁ  ed from meta-analyses by Brewin et al.  (2000) and Ozer et al. (2003))4.6.2 post-traumatic stress disorder

SECTION 4  clinical syndromes of adult psychiatry 708
but other studies have found small associations in the opposite 
direction.(41)
(c) Psychological responses during trauma
PTSD risk depends on the degree of psychological distress the traumatic event caused. The psychological impact of the trauma depends on the perceived threat to life,
(11,76) the perceived loss of 
control (helplessness),(82) and the perceived threat to one’s autonomy 
(mental defeat).(15,16)  Among the psychological responses predict-
ing PTSD are feelings of anger, guilt, or shame(83) and dissociation 
and numbing.(11)
Factors affecting recovery from trauma
(a) Recovery environment
Recovery is facilitated by social support, (11,76) and hindered by 
perceived negative responses from other people.(15,16) Further 
stressful or traumatic life events impede recovery from PTSD.(76)

This includes the stress caused by long-lasting negative effects of the event on health and personal appearance, ﬁ  nancial difﬁ  culties, 
disruptions in everyday life, and ongoing litigation.
(41,81,84)
(b) Psychological processes
Excessively negative appraisals of the traumatic event impede recovery (e.g. ‘Nowhere is safe’ , ‘I cannot trust anyone’ , ‘I am inadequate’).
(16,56)  If individuals interpret their initial PTSD symp-
toms as signs that they are going mad or losing control, or as signs of a permanent change for the worse, they are less likely to recover.
(16,41)
If individuals engage in behaviours or cognitive coping styles

(16,41)
If individuals engage in behaviours or cognitive coping styles 
that prevent them from ‘working through’ and accepting the trauma, they are less likely to recover. Such maladaptive behaviours include avoidance, not talking about the experience, safety behaviours, denial, thought suppression, and rumination.
(16,41,80,85)
Treatment of PTSD
Meta-analyses of randomized controlled trials have identiﬁ  ed 
several effective psychological and pharmacological treatments for PTSD.
(86–88)
Psychological treatments lead, on average, to large improvements in PTSD symptoms. The mean effect size (Cohen’s d statistic) for 
the difference between the pre- and post-treatment scores was d = 1.43 across 26 studies of psychological treatments.
(86) (An effect 
size d = 1 means that the treatment led to improvement by one

size d = 1 means that the treatment led to improvement by one 
standard deviation). In interpreting the effect sizes of treatments, one has to bear in mind that pill-placebo or waiting list conditions also lead to some improvement. Mean effect sizes for theseconditions were d = 0.77 and d = 0.75 for observer-rated PTSD 
symptoms, and d= 0.51 and d = 0.44 for self-rated PTSD
symptoms in 61 treatment-outcome trials.
(88)
Not all psychological treatments are equally effective in treating 
PTSD. According to the meta-analyses, trauma-focused treatments are more effective than other treatments.
(86,87) Trauma-focused 
cognitive behaviour therapy (CBT) and eye movement desensitiza-tion and reprocessing (EMDR) were superior to stress management and other therapies such as supportive therapy or hypnotherapy.
(87)

(87)
On average, 67 per cent of patients who complete the trauma-focused treatments (and 56 per cent of those who enter thesetreatments; intent-to-treat analysis) no longer met diagnostic crite-
ria for PTSD.
(86) For supportive therapy, the corresponding recov-
ery rates were 39 per cent among treatment completers and 36 per cent in intent-to-treat analyses.
(86) On the basis of these results, 
recent United Kingdom and Australian treatment guidelines recom-mend trauma-focused CBT and EMDR as the treatments of choice for PTSD.
(89,90) Both treatments address the patient’s troubling 
memories of the traumatic events and the personal meaning of the event and its consequences.
(a) Trauma-focused psychological treatments
(i) Cognitive behavioural therapy (CBT)

All effective CBT programmes for PTSD include an element of psycho-education about common reactions to trauma that nor-malizes the PTSD sufferer’s symptoms, and a rationale for the interventions. Trauma-focused CBT programmes for PTSD include either exposure or cognitive therapy, or a combination of these interventions. Some also include elements of stress management training such as breathing training.
Exposure.  Exposure treatment for PTSD comprises two compo-
nents.
(58) In imaginal exposure, patients are systematically exposed 
to the memory of the trauma. A commonly used procedure is imaginal reliving,
(58) where patients relive the traumatic event in

nents.
(58) where patients relive the traumatic event in 
their imagination, including their thoughts and feelings at the time. This is repeated until the reliving no longer evokes high levels of distress. Writing a trauma narrative can also be used as a method of exposure to the trauma memory.
(54) In vivo exposure(58) involves 
confronting (safe) situations that patients avoid because they remind them of the trauma (e.g. going to the site of the traumatic event, driving again after a road trafﬁ  c accident). Exposure is 
repeated until the patient no longer responds with high levels of distress. The effects of exposure were originally explained as an effect of habituation, but there are probably several mechanisms for its efﬁ  cacy.
(55,58)  For example, patients realize that exposure

(55,58)  For example, patients realize that exposure 
does not lead to a feared outcome (for example, going to the site of an accident will not mean that another accident will happen; think-ing about the trauma will not make them go mad) and thus helps in correcting dysfunctional beliefs about danger of the world and the meaning of PTSD symptoms. Second, the repeated exposure helps patients to create an organized memory and facilitates the distinction that intrusive thoughts and images are memories rather than something happening right now.
Whereas exposure treatment is effective in the majority of cases, 
a minority of patients become worse.
(91) In particular, exposure 
treatment does not appear suitable for patients whose traumatic memories are about being perpetrators rather than victims.
(92)
It may also have limits in treating survivors of complex and pro-longed traumatic events such as torture, war, or captivity.
(93)
Cognitive therapy.  Cognitive therapy for anxiety disorders

(92)
(93)
Cognitive therapy.  Cognitive therapy for anxiety disorders 
focuses on the identiﬁ  cation and modiﬁ  cation of misinterpreta-
tions that lead the patient to overestimate threat. In PTSD, the perceived threat stems from interpretations of the trauma and its aftermath.
(54,55)  For example, people with PTSD may feel strong 
guilt or shame related to the trauma: a rape victim may blame herself for the rape; a war veteran may feel it was his fault thathis best friend was killed. Others overestimate the current danger they are encountering in everyday life. An accident survivor may become convinced that he is at great risk of having a further trauma.

709
Others may take the intrusive re-experiencing symptoms as a sign 
that they are about to go crazy. By discussing the evidence for and against the interpretations, and by testing out the predictions derived from the interpretations with the help of the therapist, the patient arrives at more adaptive conclusions. The patient is encour-aged to drop behaviours and cognitive strategies that prevent a 
disconﬁ  rmation of the negative interpretations, e.g. excessive pre-
cautions to prevent further trauma or excessive rumination about what one could have done differently during the event. Recent studies have shown that cognitive therapy is effective on its own, without additional exposure treatment.
(91,94)  However, when ver-
bal challenging of dysfunctional beliefs was used as an additional procedure after a session of imaginal exposure, it did not lead to additional treatment gains.
(94) However, cognitive therapy may

(94) However, cognitive therapy may 
help reduce the amount of exposure necessary to achieve large treatment effects.
(95,96)
(ii) Eye-movement desensitization and reprocessing (EMDR)
Like trauma-focused CBT, EMDR(97) aims to help patients process 
their traumatic memory and think more positively about their experience. It involves inducing a series of rapid and rhythmic eye movements while the patient focuses on a trauma-related image and related negative emotions, sensations, and thoughts. Patients are instructed to visually track the therapist’s ﬁ  ngers as they move

back and forth in front of the patient’s eyes for sets of about 20 s. After each set, the patient discusses the images and emotions they experienced during the eye movements with the therapist. This process is repeated, and includes focusing on different memories that come up in connection with the trauma. Once distress to the target image is reduced, patients are instructed to focus on the image while rehearsing a positive thought connected to the image. 
The mechanism of treatment is not yet understood. Several 
empirical studies have suggested that the eye movements may not be necessary in producing the therapeutic effects observed with EMDR.
(98)
(iii) Other psychological treatments
Most other psychological treatments have a small evidence-base. In general, non-trauma focused treatments were shown to be less effective than trauma-focused treatments in randomized controlled trials.
(86,87)
Stress management (stress inoculation).  The goal of this treat-

(86,87)
ment is to teach the patient a set of skills that will help them cope with stress. Examples include relaxation training, training in slow abdominal breathing, thought stopping of unwanted thoughts, assertiveness training, and training in positive thinking. Stress management is more effective than supportive psychotherapy, but given on its own less effective than trauma-focused treatments.
(87)
Psychodynamic therapy.  Several different forms of psychody-
namic treatments for PTSD have been described.(99) The focus lies 
on resolving unconscious conﬂ  icts provoked by the stressful event

on resolving unconscious conﬂ  icts provoked by the stressful event 
by making it conscious in tolerable doses. This is thought to help the patient reengage normal mechanisms of adaptation. The goal of treatment is to understand the meaning of the stressful event in the context of the individual’s personality, attitudes, and early expe-riences. The psychological meaning of the event is explored by a range of methods such as ‘sifting and sorting through wishes, fantasies, fears, and defences stirred up by the event’ .
(99) Treatment 
strategies include exploratory insight-oriented, supportive, or directive activity. It may also include working with transference,

strategies include exploratory insight-oriented, supportive, or directive activity. It may also include working with transference, 
but with the therapist using a less strict technique than that used in psychoanalysis. T o date there is only one controlled study of psychodynamic therapy, and the effect size observed in that study is below those observed with trauma-focused CBT or EMDR.
(88)
Hypnotherapy.  The patient is given instructions to induce a state 
of highly focused attention, a reduced awareness of peripheral stimuli, and a heightened suggestibility. The goal of this treatment is to enhance control over trauma-related emotional distress and hyperarousal symptoms and to facilitate the recollection of details of the traumatic event. T o date there is only one controlled study of hypnotherapy, and the effect size observed in that study is below those observed with trauma-focused CBT or EMDR.
(88) Shalev

(88) Shalev 
et al.(93) raised concerns about the use of hypnotherapy in the treat-
ment of PTSD as it may induce dissociative states.
Supportive therapy.  Supportive therapy is primarily non-directive 
and non-advisory. Through a supportive therapeutic relationship, clients are encouraged to explore their thoughts, feelings, and behaviour to reach clearer self-understanding; and to ﬁ  nd and 
use their strengths so that they cope more effectively with their lives 
by making appropriate decisions, or by taking relevant action. Supportive therapy is less effective than trauma-focused psycho-
logical treatments.
(86,87)
Although recent guidelines(89,90) recommend trauma-focused psy-
chological treatments as the ﬁ  rst line treatments for PTSD, they 
also acknowledge a role for medication. A Cochrane review(100)

found an advantage of medication over placebo with response rates of 59.1 and 38.5 per cent, respectively. Indications for medication according to recent guidelines include patient choice, severe ongoing threat, the patient is too depressed or unstable to engage in psychological treatment, and failure to respond to psychological treatment.
(a) Selective serotonin-reuptake inhibitors (SSRIs)
Among the pharmacological treatments, the SSRIs have been most widely studied and are recommended as the ﬁ  rst line medication 
choice for PTSD according to expert consensus
(90,101) and a recent 
Cochrane review.(100) Paroxetine has received the most consistent 
support for its efﬁ  cacy.(89,100) SSRIs reduce alcohol consumption; a 
relevant ﬁ  nding given the high comorbidity of PTSD with sub-

stance abuse or dependency.(102)
(b) Monoamine oxidase inhibitors (MAOIs)
There is some evidence that phenelzine is effective in PTSD,(89,100)
particularly in reducing re-experiencing symptoms and insom nia.(102)
Thus, phenelzine may be considered as one of the treatment options 
for PTSD by mental health specialists,(89) taking into consideration 
the risks and necessary dietary restrictions.
(c) Other antidepressants
There is some evidence for the efﬁ  cacy of tricyclic antidepressants, 
particularly amitriptyline, in the treatment of PTSD.(89,100)
They may be considered as a treatment option for PTSD by mental health specialists.
(89,90) Mirtazepine, a noradrenergic and speciﬁ  c 
serotonergic antidepressant, has shown promise in initial trials and has been recommended as one of the treatment options for PTSD.

(89,90)4.6.2 post-traumatic stress disorder

SECTION 4  clinical syndromes of adult psychiatry 710
Benzodiazepines do not appear to be effective in the treatment of 
PTSD. They do not affect the re-experiencing, avoidance, and numb-ing symptoms, although they may show some effects on insomnia, irritability, and general anxiety and arousal symptoms.
(102)
Advice on management
Diagnosing PTSD
When assessing whether a patient has experienced a trauma, it is important to ask about speciﬁ  c examples of traumatic events. 
Patients may initially feel too overwhelmed or ashamed to report details of their traumatic experience, and may ﬁ  nd it easier to 
reply to factual questions with ‘yes’ or ‘no’ answers. In diagnosing PTSD, clinicians need to ascertain that the patient involuntarily re-experiences parts of the event. In addition, patients will need to have some symptoms of hyperarousal, avoidance, and emotional numbing. Self-report instruments such as the Post-traumatic Stress Diagnostic scale

(28) or semi-structured interviews such as the 
Clinician Administered PTSD scale(25) are useful in assessing the 
pattern and severity of symptoms. Clinicians should ask about the impact of the symptoms (e.g. distress, restrictions, effect on family and work) on the patient’s life. The DSM-IV criterion of a minimum of three avoidance or numbing symptoms appears too strict for clinical purposes. It does not appear justiﬁ  ed to with-
hold treatment if the patient is disabled by the PTSD symptoms but fails to meet this criterion.
Is PTSD the main problem?

As PTSD is often comorbid with other disorders, clinicians need to ascertain whether PTSD is the main problem for which the patient presently needs help at present. The time course of the onset of the comorbid disorders and changes in the severity of symptoms provide useful information. It is also helpful to ask patients whether they believe that they would need professional help for their other problems if the PTSD symptoms are resolved. In cases of comorbid depression, the PTSD should usually be treated ﬁ  rst (as 
comorbid depression improves with successful PTSD treatment), unless the depression is so severe that the patient cannot engage in 
treatment. In contrast, signiﬁ  cant substance dependence usually 
needs to be addressed before treating the PTSD.
(89)
Assessments need to include a risk assessment. If there is a high

(89)
Assessments need to include a risk assessment. If there is a high 
risk of suicide or harm to others, clinicians will need to concentrate on managing the risk ﬁ  rst.
(89)
Clinicians will also need to establish whether there is any serious 
ongoing threat or health, social, and ﬁ  nancial problems that may 
need to be addressed before the patient can engage in psychological 
treatment.(89)
(a) Choice of treatment
Patients should be informed about effective treatments for PTSD. Information material for patients and carers is available.
(103)
Trauma-focused psychological treatments are the best treatment option for PTSD to date, given the strong evidence for their effectiveness,
(89,90) their established long-term effectiveness,(88)

(103)
and the lower dropout rates compared to medication. Meta-analysesreport that, across studies, 14–21 per cent of the patients can be expected to dropout of psychological treatments,
(86,88) compared 
to 31–36 per cent for medication.(88,100)  The advantage of SSRIs and other medications compared to psychological treatments is 
that they are more readily available.
(i) Psychological treatment
Trauma-focused psychological treatments usually last between 8 and 12 sessions (longer for patients with multiple traumas and comorbid personality disorders). When the trauma is discussed in the session, 90 min should be allowed for the session.
(89,90)  The 
treatments require a good therapeutic alliance.(90) Depending

treatments require a good therapeutic alliance.(90) Depending 
on the nature of the trauma and comorbid problems, additional sessions for establishing trust and emotional stabilization may be needed before the trauma-focused treatment commences.
(89,90)
(ii) Pharmacological treatment
Clinicians should discuss the beneﬁ  ts and possible side effects of 
the prescribed medication with the patient, and address common concerns, such as fears of addiction. Patients also need to be informed that the medication needs to be discontinued gradually. Most antidepressants recommended for the use in PTSD need to be discontinued over at least 4 weeks.
(89) The risk of self-harm needs 
to be considered when prescribing antidepressants. Those with high risk should be seen at least weekly until the risk is no longer considered signiﬁ  cant.
(89,90)  Patients receiving SSRIs need to be

(89,90)  Patients receiving SSRIs need to be 
monitored for akathisia, suicidal ideation, and increased anxiety and agitation. Patients receiving phenelzine require careful moni-toring (including blood pressure measurement) and advice about interactions with other medicines and food.
(89)
(b) Special problems in the management of PTSD patients
Avoidance is one of the main symptoms of PTSD, and it can thus take years for the patient to seek help for this condition. It is important for clinicians to bear in mind that even those who seek help may ﬁ  nd it hard to talk about the traumatic experience, and 
may show signs of avoidance such as irregular attendance orfailure to disclose the worst moments of the trauma initially. Therapeutic techniques to deal with this problem includeempathy, gradual encouragement, and giving the patient control over the timing and mode of working through the experience(e.g. writing, talking into a tape recorder, reliving with the support of the therapist).

One of the requirements for change is that the patient feels safe. 
Therapists therefore have to make sure that they establish a good relationship with the patient, and that the therapeutic setting or 
their behaviour does not remind the patient of the traumatic event. 
Sometimes support in changing living circumstances may be nec-essary if they prevent the patient from being safe (e.g. moving house if assaulted by a neighbour).
Patients with PTSD often suffer from poor sleep and concentra-
tion, and ﬁ  nd it painful to face reminders of the trauma. For these 
reasons, they have difﬁ  culty in dealing with the aftermath of trau-
matic events such as legal procedures and continuing treatment for physical injuries, including the long delays that this usually involves. Such ongoing stressors impede recovery, and patients may there-fore beneﬁ  t from problem-solving and practical advice.
National Institute of Clinical Excellence. (2005). Clinical guideline 26:

National Institute of Clinical Excellence. (2005). Clinical guideline 26: 
post-traumatic stress disorder: the management of PTSD in adults and children in primary and secondary care. http://guidance.nice.org.uk/CG26

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in victims of violent crime. The role of shame, anger, and childhood abuse. Journal of Abnormal Psychology ,109, 69–73.
84. Carr, J.V ., Lewin, T.J., Webster, R.A., et al. (1997). Psychosocial 
sequelae of the 1989 Newcastle earthquake. II. Exposure and morbidity 
proﬁ les during the ﬁ  rst 2 years post-disaster. Psychological Medicine ,
27, 167–78.
85. Joseph, S., Dalgleish, T., Williams, R., et al. (1997). Attitudes towards 
emotional expression and post-traumatic stress in survivors of the Herald of Free Enterprise disaster. The British Journal of Clinical 
Psychology ,36, 133–8.

86. Bradley, R., Greene, J., Russ, E., et al. (2005). A multidimensional 
meta-analysis of psychotherapy for PTSD. The American Journal of 
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87. Bisson, J., Ehlers, A., Matthews, R., et al. (2007). Systematic review and 
meta-analysis of psychological treatments for post-traumatic stress disorder. The British Journal of Psychiatry ,190, 97–104.
88. Van Etten, M.L. and Taylor, S. (1998). Comparative efﬁ  cacy of 
treatments for post-traumatic stress disorder: a meta-analysis. Clinical
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89. National Institute of Clinical Excellence. (2005). Clinical guideline 26: 
post-traumatic stress disorder: The management of PTSD in adults and children in primary and secondary care. http://guidance.nice.org.uk/CG26
90. Australian Centre for Posttraumatic Mental Health. Australian

90. Australian Centre for Posttraumatic Mental Health. Australian 
Guidelines for the treatment of acute stress disorder and
posttraumatic stress disorder. http://www.acpmh.unimelb.edu.au/
91. Tarrier, N., Pilgrim, H., Sommerﬁ  eld, C., et al. (1999). A randomised 
trial of cognitive therapy and imaginal exposure in the treatment of chronic post traumatic stress disorder. Journal of Consulting and 
Clinical Psychology ,67, 13–9.
92. Foa, E.B. and Meadows, E.A. (1997). Psychosocial treatments for 
post-traumatic stress disorder: a critical review. Annual Review of 
Psychology ,48, 449–80.
93. Shalev, A.Y., Bonne, O., and Eth, S. (1996). Treatment of
post-traumatic stress disorder: a review. Psychosomatic Medicine ,
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94. Marks, I.M., Lovell, K., Norshirvani, H., et al. (1998). Treatment 
of post-traumatic stress disorder by exposure and/or cognitive restructuring. Archives of General Psychiatry
,55, 317–25.

95. Ehlers, A., Clark, D.M., Hackmann, A., et al. (2003). A randomized 
96. Ehlers, A., Clark, D.M., Hackmann, A., et al. (2005). Cognitive therapy 
for PTSD: development and evaluation. Behaviour Research and 
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97. Shapiro, F. (1995). Eye movement desensitization and
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99. Kudler, H.S., Blank, A., and Krupnick, J.L. (2000). Psychodynamic 
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org.uk/CG26
4.6.3 Recovered memories 
and false memories
Clinicians working with survivors of traumatic experiences have

Clinicians working with survivors of traumatic experiences have 
frequently noted the existence of memory loss with no obvious physical cause and the recovery of additional memories during clinical sessions. Indeed, amnesia is described in diagnostic manu-als as a feature of post-traumatic stress disorder, although its pres-ence is not necessary for this diagnosis. In the majority of these cases, people forget details of the traumatic event or events, or for-get how they reacted at the time, although they remember that the event happened. They typically report that they have endeavoured not to think about the event, but have never forgotten that it occurred. Controversy is centred on memories of traumatic events, particularly concerning child abuse, that appear to be recovered after a long period of time in which there was complete forgetting that they had ever happened. It has sometimes been suggested that

many, if not all, of these apparent recovered memories are the 
product of inappropriate therapeutic suggestion. This argument has been promulgated in particular by the False Memory Syndrome Foundation in the United States, by its counterpart, the British False Memory Society, and by their scientiﬁ  c advisors.
The ‘false memory’ position
Loftus(1) suggested that at least some of the memories of child 
sexual abuse recovered in therapy after apparent total amnesia may not be veridical, but may be false memories encouraged or 
‘implanted’ by therapists who have prematurely decided that the 
patient is an abuse victim and who use inappropriate therapeutic 
techniques to persuade him or her to recover corresponding

techniques to persuade him or her to recover corresponding 
‘memories’ . The false memory societies have claimed that thereare many cases known to them in which previously happy families have been disrupted by accusations of abuse that were onlytriggered when an adult child entered therapy. Particular scepti-cism has been levelled at reports of repeated abuse, all of whichhas apparently been forgotten, and it has been claimed that such reports are contradicted by what is known scientiﬁ  cally about 
memory. Reports of ‘repressed’ memories of childhood abuse are generally regarded as clinical speculations and the psychoanalytical concept of repression as one that has no credible scientiﬁ  c support. 4.6.3 recovered memories and false memories

SECTION 4  clinical syndromes of adult psychiatry 714
Several reviewers claim that there is no empirical support for 
repression or dissociative amnesia in trauma victims.(2–4)
Lindsay and Read(5) have marshalled evidence to suggest that the 
creation of false memories within therapy is a possibility that must be taken seriously. For example, they review experimental studies conducted with non-clinical subjects concerning the fallibility and malleability of memory, and note the potential for inaccurate recall involved in techniques such as hypnosis. Experiments have demon-strated that people are sometimes confused about whether a recent event in the laboratory actually happened, or whether they only imagined it happening. Other experiments have repeatedly succeeded in implanting apparent childhood memories of single non-abusive events in approximately 25 to 30 per cent of subjects, particularly in those who score highly on measures of hypnotiz-ability or suggestibility.

(6) Further evidence comes from individuals 
who claim to remember impossible events such as being kidnapped by aliens.
(4)
Critics have argued that these experiments are a long way from 
being evidence that therapists could implant false memories of child abuse, and even the experimental studies have shown that successful suggestion depends on the plausibility of the event subjects are asked to believe in. Nevertheless, although no one has performed experiments in an attempt to implant the notion that abuse occurred, it is reasonable to argue that some patients may be highly suggestible and inclined to go along with the beliefs of therapists who may be their only source of support. If their thera-pist was convinced that abuse had occurred, put overt or covert pressure on their patient to ‘remember’ this abuse, and was insufﬁ  -
ciently alert to the unreliability of memory, there would be a greatly increased risk of false memories occurring.

In conclusion, the recently developed ‘false memory’ position 
goes beyond previous concerns of a general nature about errors in memory, and speciﬁ  cally identiﬁ  es a process whereby errors arise 
after a person has been subjected to repeated suggestive inﬂ  uences 
that the explanation for their symptoms lies in forgotten child sexual abuse. These inﬂ  uences are usually thought to occur in therapy,

that the explanation for their symptoms lies in forgotten child sexual abuse. These inﬂ  uences are usually thought to occur in therapy, 
although it has been proposed that exposure to certain books or broadcast media may have the same effect. This position relies partly on information from the false memory societies about their members, and partly on experimental evidence from non-traumatic procedures in the laboratory. There has been little independent scrutiny of the data from members of false memory societies, and many of their claims, for example that parents have been falsely accused, that accusations only follow entry into therapy, or that there is a ‘false memory syndrome’ , are anecdotal and have not been empirically veriﬁ  ed.
(7)
Evidence for genuine ‘recovered memories’
Over 20 longitudinal and retrospective studies have now found that

(7)
Over 20 longitudinal and retrospective studies have now found that 
a substantial proportion of people reporting child sexual abuse (somewhere between 20 and 60 per cent) report periods in their lives (often lasting for several years) when they could not remem-ber that the abuse had taken place.
(8,9) Although the rates vary 
between studies, broadly similar ﬁ  ndings have been obtained by 
clinical psychologists, psychiatrists, and cognitive psychologists in both clinical and community samples. As has been pointed out by critics of these studies, this evidence supports the forgetting of trauma, but does not yet have much to say about the mechanism (for example ‘repression’) by which it occurs. Thus it would be true 
to say that while there is evidence for forgetting, there is little evidence for ‘repression’ as such.
Three main factors support the argument that these apparently 
forgotten memories are not necessarily false.

1 Surveys have also found recovered memories of other traumatic 
experiences such as witnessing accidents, experiencing medical procedures, and physical abuse in childhood.
(10) It is unclear 
how these could have been brought about by suggestion.
2 A number of studies have found that apparent recovered memo-
ries occur prior to any therapy, and in the absence of any obvious prolonged suggestive inﬂ  uence.
(11) Again, it is unclear how these 
could have been brought about by suggestion.
3 Surveys of psychologists and therapists found that approximately

3 Surveys of psychologists and therapists found that approximately 
40 per cent of those with apparent recovered memories reported corroborative evidence for the content of the memories, such as abusers’ confessions, testimony from other victims, and court records. Although the quality of this corroboration has been criticized, it seems unlikely that all these cases can be summarily dismissed. There are also substantial numbers of case studies reporting more detailed corroborative evidence for apparent recovered memories, some of this evidence of reasonably high quality.
(10–12)
The quality of the research evidence supporting genuine recov-
ered memories is mixed, and almost all the studies can be argued to have some ﬂ  aws, but taken together the evidence for genuine mem-

ories of major traumatic events is far more extensive than the evidence for false memories of such events. Moreover, these obser-vations need not, as has sometimes been claimed, contradict what we know about memory. Cognitive psychology recognizes that ordinary memory relies as much for its efﬁ  ciency on the ability 
to inhibit unwanted material as on the ability to gain rapid access to relevant material. Experimental studies clearly demonstrate the inhibition of memory retrieval and the existence of a subgroup of individuals with poor memories for negative experiences.
(11)
The intimate neuroanatomical connections between brain

(11)
The intimate neuroanatomical connections between brain 
circuits involved in emotion and those involved in memory provide a good reason for believing that memory may not behave in the same way under conditions of extreme real-world stress as it does in ordinary laboratory experiments. Whereas high levels of arousal often make events more difﬁ  cult to forget, it has been 
argued by several well-known neuroscientists that extraordinarily high levels of catecholamines or other neuropeptides at the time of the trauma, perhaps in combination with a failure to release sufﬁ  -
cient cortisol, may produce amnesia. More speciﬁ  cally, it has been 
suggested that extreme stress produces at the same time both enhanced fear conditioning and impaired autobiographical memo-ry.
(13) Much of the evidence is indirect and not yet compelling, but

(13) Much of the evidence is indirect and not yet compelling, but 
it illustrates that claims concerning recovered memories of trauma need not violate current knowledge concerning the cognitive psy-chology and neurobiology of memory.
Why the debate?
From a purely scientiﬁ  c point of view, it should be evident that the 
quality of the available evidence is insufﬁ  cient to justify any extreme 
position at present. The questions are extremely difﬁ  cult to study

715
empirically, and there has been little new research since the 1990s 
to suggest that this state of affairs is likely to change. However, scientiﬁ  c considerations have sometimes been secondary to the 
passionate advocacy practised by parents who claim to be falsely accused, and by accusers who claim that their memories of abuse are being ignored. Psychiatrists and psychologists have in the past become caught up in the debate and in some cases abandoned any pretence at neutrality. In the face of these compelling and intensely painful personal concerns, the quality of much of the argument became debased. Thus, supposedly scientiﬁ  c contributions on both 
sides of this debate questioned the motives and integrity of people with whom they disagreed and attempted to disparage opponents’ professional abilities. Some of these same authors made exclusive claims for the scientiﬁ  c legitimacy of their own perspective, sub-
jecting opposing data to ﬁ  erce scrutiny while being relatively

jecting opposing data to ﬁ  erce scrutiny while being relatively 
uncritical of studies that supported their point of view. Much of the literature was obfuscatory and confusing. Logical errors abounded, seen for example in the conclusion that because a memory has been recovered in therapy, the practitioner must have been using ‘recovered memory therapy’ .
A good example of the debate in action is the article by Pope 
et al.
(4) on the evidence for dissociative amnesia in trauma victims 
and the commentary that followed it.(14) These articles demon-
strate how widely differing conclusions can be drawn from the same set of studies, depending on the way terms are deﬁ  ned, 
on assumptions about what evidence should be given the most weight, and on the rigour with which alternative explanations are evaluated.
An emerging scientiﬁ  c and professional 
consensus
What should be clear by now is that extreme views, claiming that

consensus
What should be clear by now is that extreme views, claiming that 
either false memories or genuine recovered memories are rare or impossible, cannot be supported by the available data. Nevertheless, the dispute continues about whether traumatic events, and particu-larly repeated traumas, can be forgotten and then remembered with essential accuracy. In my view it is safe to conclude from the evidence reviewed that the hypothesized implantation of false memories by practitioners cannot account for more than a subset of recovered memories (and at present it is entirely unclear how large or small this subset might be). False memories may certainly arise in other circumstances, but as yet there is little pertinent evidence. On the other hand, there is a great deal of plausible evidence sup-porting the existence of genuine recovered memories.
Most commentators, including some members of the advisory 
boards of false memory societies,

(6) now accept that traumatic 
events can be forgotten and then remembered. Cognitive psycholo-gists Lindsay and Read
(5) summed it up well: ‘In our reading, 
scientiﬁ  c evidence has clear implications . . . memories recovered 
via suggestive memory work by people who initially denied any such history should be viewed with scepticism, but there are few grounds to doubt spontaneously recovered memories of common forms of child sexual abuse or recovered memories of details of never-forgotten abuse. Between these extremes lies a grey area within which the implications of existing scientiﬁ  c evidence are 
less clear and experts are likely to disagree’ . Similarly, the consensus view among independent commentators, repeated in the 1995 report of the British Psychological Society’s Working Party on

less clear and experts are likely to disagree’ . Similarly, the consensus view among independent commentators, repeated in the 1995 report of the British Psychological Society’s Working Party on 
Recovered Memories and the 1995 interim statement of the American Psychological Association’s Working Group on Investigation of Memories of Childhood Abuse, is that memories may be recovered from total amnesia and they may sometimes be essentially accurate. Equally, such ‘memories’ may sometimes be inaccurate in whole or in part.
In practical terms, the debate has had two major effects. First, 
proponents of ‘recovered memory therapy’ are now almost impossible to ﬁ  nd within the ranks of leading psychiatrists and 
psychologists. Despite the small amount of empirical support, there is widespread agreement that situations in which there is sustained suggestive inﬂ  uence, such as therapy, do have the poten-

tial to induce false memories. Active attempts to recover suspected forgotten memories may sometimes be appropriate in unusual or extreme cases, but both the client and the therapist must be aware of the risk of false memories. T echniques such as hypnosis and guided imagery should not be used without safeguards against potential suggestive inﬂ  uence. Second, good practice now requires 
both the therapist and the client to adopt a critical attitude towards any apparent memory that is recovered after a period of amnesia, whether or not this is within a therapeutic context, and not to assume that it necessarily corresponds to a true event. Even highly 
vivid traumatic memories (sometimes known as ‘ﬂ  ashbacks’) may

vivid traumatic memories (sometimes known as ‘ﬂ  ashbacks’) may 
be misleading or inaccurate in some cases. Clinical guidelines are now available to help the practitioner avoid the twin perils of uncritically accepting false memories as true or summarily dismiss-ing genuine recovered memories.
(9,15)
Brewin, C.R. (2003). Posttraumatic stress disorder: malady or myth?  Y ale 
University Press, New Haven, CT (see Chapters 7 and 8).
Davies, G.M. and Dalgleish, T. (eds.) (2001). Recovered memories: seeking 
the middle ground . Wiley, Chichester.
 1. Loftus, E.F. (1993). The reality of repressed memories. The American 
Psychologist ,48, 518–37.
 2. Pope, H.G. and Hudson, J.I. (1995). Can memories of childhood abuse 
be repressed? Psychological Medicine ,25, 121–6.
 3. Pope, H.G., Hudson, J.I., Bodkin, J.A., et al. (1997). Can trauma victims 
develop ‘dissociative amnesia’? the evidence of prospective studies. The British Journal of Psychiatry ,172, 210–15.

3. Pope, H.G., Hudson, J.I., Bodkin, J.A., et al. (1997). Can trauma victims 
 4. McNally, R.J. (2003). Remembering trauma.  Harvard University Press, 
Cambridge, Mass.
 5. Lindsay, D.S. and Read, J.D. (1995). ‘Memory work’ and recovered 
memories of childhood sexual abuse: scientiﬁ  c evidence and public, 
professional and personal issues. Psychology, Public Policy and the Law ,
1, 846–908.
 6. Wright, D., Ost, J., and French, C.C. (2006). Recovered and false 
memories. The Psychologist ,19, 352–5.
 7. Pope, K.S. (1996). Memory, abuse and science: questioning claims 
about the False Memory Syndrome epidemic. The American 
Psychologist ,51, 957–74.
 8. Gleaves, D.H., Smith, S.M., Butler, L.D., et al. (2004). False and 
recovered memories in the laboratory and clinic: a review of experimental and clinical evidence. Clinical Psychology: Science and 
Practice ,11, 3–28.

 9. Mollon, P . (1998). Remembering trauma: a psychotherapist’s guide to 
memory and illusion . Wiley, Chichester.4.6.3 recovered memories and false memories

SECTION 4  clinical syndromes of adult psychiatry 716
10. Andrews, B., Brewin, C.R., Ochera, J., et al. (1999). The characteristics, 
context, and consequences of memory recovery among adults in therapy. The British Journal of Psychiatry ,175, 141–6.
11. Brewin, C.R. (2003). Posttraumatic stress disorder: malady or myth?
Y ale University Press, New Haven, Conn.
12. Cheit, R. (2005). The recovered memory project . Internet posting 
http://www.brown.edu/Departments/Taubman_Center/Recovmem/
Archive.html
13. Elzinga, B.M. and Bremner, J.D. (2002). Are the neural substrates of 
memory the ﬁ  nal common pathway in posttraumatic stress disorder 
(PTSD)? Journal of Affective Disorders ,70, 1–17.
14. Brewin, C.R. (1998). Commentary: questionable validity of 
‘dissociative amnesia’ in trauma victims. The British Journal 
of Psychiatry ,172, 216–17.
15. Pope, K.S. and Brown, L.S. (1996). Recovered memories of abuse: 
assessment, therapy, forensics . American Psychological Association,

assessment, therapy, forensics . American Psychological Association, 
4.6.4 Adjustment disorders
James J. Strain, Kimberly Klipstein, 
and Jeffrey Newcorm
The psychiatric diagnoses that arise between normal behaviour 
and major psychiatric morbidities constitute the problematic sub-threshold disorders. These subthreshold entities are also juxtaposed between problem-level diagnoses and more clearly deﬁ  ned disor-
ders. Adjustment disorder (AD) would ‘trump’ problem-level dis-orders, but would be ‘trumped’ by a speciﬁ  c diagnosis even if it 
were in the NOS category. The subthreshold disorders present major taxonomical and diagnostic dilemmas in that they are often poorly deﬁ  ned, overlap with other diagnostic groupings, and have 
indeﬁ  nite symptomatology. It is therefore not surprising that issues

indeﬁ  nite symptomatology. It is therefore not surprising that issues 
of reliability and validity prevail. One of the most commonly employed subthreshold diagnosis that has undergone a major evo-lution since 1952 is AD (Table 4.6.4.1). The advantage of the indef-initeness of these subthreshold disorders is that they permit the 
classiﬁ  cation of early or prodromal states when the clinical picture 
is vague and indistinct, and yet the morbid state is in excess of that expected in a normal reaction and this morbidity needs to be iden-tiﬁ ed and often treated. Therefore, AD has an essential place in the 
psychiatric taxonomy.
Many questions prevail with regard to the concept of the AD 
diagnosis: (1) the role of stressors and the place of speciﬁ  c stress-
ors; (2) the importance of age; (3) the role of concurrent medical morbidity, for example comorbidity of Axis I and/or Axis III disor-ders; (4) the lack of speciﬁ  city of the diagnostic criteria; (5) the

absence of a symptom checklist; (6) uncertainty as to optimal treat-ment protocols; and (7) undocumented prognosis or outcomes. Research data regarding these questions will be examined.
The DSM was conceptually designed with an atheoretical frame-
work to encourage psychiatric diagnoses to be derived on phenom-enological grounds with an avowed dismissal of pathogenesis or aetiology as diagnostic imperatives. In frank contradiction to this atheoretical conceptual framework, the stress-induced disorders require the inclusion of an aetiological significance to a life

event—a stressor—and the need to relate the stressor’s effect on the patient in clinical terms. However, the stress-related disorders are unique in that they are psychiatric diagnoses with a known aetiology—the stressor—and thus aetiology is essential for the diagnosis. Four other diagnostic categories also invoke aetiology in their diagnostic criteria: (1) organic mental disorders (aetiology-physical abnormality); (2) substance abuse disorders (aetiology-ingestion of substances); (3) post-traumatic; and (4) 
acute stress disorders
AD is a stress-related phenomenon in which the stressor precipi-

tates maladaptation and symptoms that are time limited until either the stressor is diminished or eliminated, or a new state of adaptation to the stressor occurs (Table 4.6.4.2). At the same time that AD was evolving, other stress-related disorders, for example, post-traumatic stress disorder and acute stress disorder were described. (Acute stress disorder was formulated by Spiegel during the development of the DSM-IV .
(1,2)) Acute stress reactions could 
result from involvement in a natural disaster such as a ﬂ  ood, or an 
avalanche, or a cataclysmic personal event, for example, loss of a body part (aetiology-an identiﬁ  able stressor).
The diagnosis of AD also requires a careful titration of the tim-

ing of the stressor in relation to the adverse psychological sequelae that ensue. Maladaptation and disturbance of mood should occur within 3 months of the patient experiencing the stressor. Until the DSM-IV criteria, the ADs were regarded as transitory diagnoses that should not exceed 6 months in duration. Thereafter, that diag-nostic appellation could not be employed and had to be changed to a major psychiatric disorder or discontinued.
Deﬁ nition and history
With the opportunity in 1994 to develop another evolutionary step 
of the DSM, i.e. DSM-IV ,(3) the authors were asked to re-examine 
the subthreshold diagnostic category of AD with the goal of Table 4.6.4.1  DSM-IV Evolution of the diagnosis for adjustment 
disorder
(a) The development of emotional or behavioural symptoms in response to

disorder
(a) The development of emotional or behavioural symptoms in response to 
   an identiﬁ  able psychosocial stressor(s), which occurs within 3 months of 
the onset of the stressor(s)
(b)  These symptoms or behaviours are clinically signiﬁ  cant as evidenced by 
either of the following
 1  Marked distress that is in excess of what would be expected from 
exposure to the stressor
 2 Signiﬁ  cant impairment in social or occupational (academic) functioning(c)  The stress-related disturbance does not meet the criteria for any speciﬁ  c 
Axis I disorder and is not merely an exacerbation of a pre-existing Axis I or Axis II disorder
(d) The symptoms do not represent bereavement(e)  Once the stressor (or its consequences) has terminated, the symptoms 
do not persist for more than an additional 6 moths
Acute:  if the disturbance lasts less than 6 months.
Persistent/chronic:  if the disturbance lasts for 6 months or longer

717
improving its acknowledged ‘shortcomings’ . The research included: 
review of the literature, reanalysis of existing studies of AD and their data sets, and examination of ﬁ  eld studies (e.g. minor depres-
sion, minor anxiety) to observe if there was sufﬁ  cient differentia-
tion among these minor disorders from the ADs (e.g. how often was a stressor identiﬁ  ed in those patients assigned the diagnosis; 
minor depression or minor anxiety?). From these three sources and consultations, modiﬁ  cations for DSM-IV and their rationale were 
formulated based on the best evidence extant.
Changes in the criteria for adjustment disorder 
in DSM-IV
The review of the literature, the reanalysis of the Western Psychiatric 
Institute and Clinic data (University of Pittsburgh), and consulta-tions with experts supported the following changes in DSM-IV .
1 Enhance the understanding of the language.2 Describe the timing of the reaction to reﬂ  ect the duration of the

1 Enhance the understanding of the language.2 Describe the timing of the reaction to reﬂ  ect the duration of the 
AD: acute  (less than 6 months) or chronic  (6 months or greater).
3 Allow for the continuation of the stressor for an indeﬁ  nite period; 
psychological reactions to chronic stress states (e.g. chronic arthritis, HIV , abuse by an alcoholic spouse) do not necessarily terminate at 6 months, nor do they necessarily lead to a major psychiatric disorder.
4 Eliminate the subtypes of mixed emotional features, work (or 
academic) inhibition, withdrawal, and physical complaints (as 
they were rarely employed by diagnosticians).
Although it might be argued that ADs could be placed in a new

Although it might be argued that ADs could be placed in a new 
category of ‘stress response syndromes’ , the literature and research reports did not support such a taxonomical organization. Another possibility was that AD could be eliminated altogether, with the advantage of maintaining the atheoretical approach of the DSM conceptual framework, and substitute in its place the appropriate minor or NOS categories as established by the accompanying mood 
states or behaviours. However, these solutions do not seem appro-priate with recent ﬁ  ndings that demonstrate AD to be a valid and 
frequently employed diagnosis.
(4) AD was diagnosed in over 60 per 
cent of burned inpatients,(5) over 20 per cent of patients in early 
stages of multiple sclerosis,(6) and over 40 per cent of poststroke 
patients.(7) Furthermore, evaluations of patients in a psychiatric

patients.(7) Furthermore, evaluations of patients in a psychiatric 
walk-in clinic showed a signiﬁ  cant difference in the symptom pro-
ﬁ le of those assigned AD and the other diagnosis, including minor 
diagnoses.(8) (The McArthur ﬁ  eld trials on the prospective assess-
ment of minor depressive and anxiety disorders which collected data on the occurrence of stressors immediately preceding the out-break of symptoms are important databases that need further study to establish whether stress per se is a distinguishing characteristic between AD and the other minor mood disorders.)
Problems with the adjustment disorder diagnosis
(a) The symptom proﬁ  le
Critics of the AD diagnosis argue that the symptom complex is too 
subjective or ‘depends structurally on clinical judgement’ as opposed to sound, operational criteria.
(9,10) Because of the lack of

(9,10) Because of the lack of 
any quantitative behavioural or operational criteria, the problem of reliability and validity are obvious. Criterion reference was evalu-ated by Aoki  et al.
(11) who reported that three psychological tests, 
Zung’s Self-Rating Anxiety Scale,(12) Zung’s Self-Rating Depression 
Scale,(13) and the Proﬁ  le of Mood States,(14) were useful tools for 
the diagnosis of AD in physical rehabilitation patients. While these measures succeeded in reliably differentiating AD patients from normal patients, they were not able to distinguish them from patients with major depression or post-traumatic stress disorders. Thus, the construct of AD is designed as a means for classifying psychiatric conditions having a symptom proﬁ  le that is at the

time of its application insufﬁ  cient to meet the more speciﬁ  cally 
operationalized criteria for the major syndromes but is:
1 clinically signiﬁ  cant and deemed to be in excess of a normal 
reaction to the stressor in question;
2 associated with impaired vocational or interpersonal functioning;3 not solely the result of a psychosocial problem (V Code) requir-
ing medical attention (e.g. non-compliance, phase of life prob-lem, etc.).
However, ﬁ  eld studies are being performed
(15) to assess whether 
a reliable checklist from an elaborate list of symptoms associated with AD can be constructed (Table 4.6.4.3). (The V Codes—a problem level of diagnoses—are understandably devoid of a symptom-based diagnostic schema.)Table 4.6.4.2  ICD-10 deﬁ  nition of adjustment disorder
(a)  Onset of symptoms must occur within 1 month of exposure to an 
 identiﬁ  able psychosocial stressor, not of an unusual or catastrophic type

(b)  The individual manifests symptoms or behavioural disturbances of the 
 types found in any of the affective disorders (except for delusions and hallucinations), any disorders in F40–F48 (neurotic, stress-related, and 
somatoform disorders) and conduct disorders, but the criteria for an 
individual disorder are not fulﬁ  lled. Symptoms may be variable in both form and severity
The predominant feature of the symptoms may be further speciﬁ  ed by use of 
 a ﬁ  fth character:
 Brief depressive reaction
 Prolonged depressive reaction
 Mixed anxiety and depressive reaction
 With predominant disturbance of other emotions
 With predominant disturbance of conduct With mixed disturbance of emotions and conduct
 With other speciﬁ  ed predominant symptoms
(c)  Except in prolonged depressive reaction, the symptoms do not persist

With other speciﬁ  ed predominant symptoms
(c)  Except in prolonged depressive reaction, the symptoms do not persist 
 for more than 6 months after the cessation of the stress or its consequences. However, this should not prevent a provisional diagnosis 
being made if this criterion is not yet fulﬁ  lled
Table 4.6.4.3  DSM-IV subtypes of adjustment disorders
Adjustment disorder with depressed mood
Adjustment disorder with anxious moodAdjustment disorder with mixed anxiety and depressed moodAdjustment disorder with disturbance of conductAdjustment disorder with mixed disturbance of emotions and conductAdjustment disorder unspeciﬁ  ed4.6.4 adjustment disorders

SECTION 4  clinical syndromes of adult psychiatry 718
(b) The meaning of ‘maladaptive’
The imprecision of the diagnostic criteria for AD is immediately 
apparent in the DSM-IV description of this disorder as a maladap-tive reaction to an identiﬁ  able psychosocial stressor, or stressors 
that occurs within 3 months after onset of the stressor. It is assumed 
that the disturbance will remit soon after the stressor ceases or, if 
the stressor persists, when a new level of adaptation is achieved.
(1)
In addition to the problem of no symptom checklist, difﬁ  culties are 
inherent within each of these diagnostic elements.
First, with regard to the ‘maladaptive reaction’ , it is unclear how 
this concept can or should be operationalized. Is the assessment of maladaptation subjective or objective? Who makes the decision—a third party, a mental health professional, the patients themselves, 
or an admixture of these? Is this decision ‘culture bound’? Succinctly

or an admixture of these? Is this decision ‘culture bound’? Succinctly 
when does an individual cross the threshold into ‘patienthood’ , and who will make the decision? Powell and McCone (2004) make this point in their case report of the treatment of a patient with AD secondary to the stressors of the 11 September terrorist attacks. Since there has never before been a large-scale terrorist attack in United States, how are clinicians to know what a ‘normal’ response to such an event would be?
(16)
(c) The stressor
Most recently, in the DSM-IV text revision (DSM-IV-TR; American Psychiatric Association, 2000),
(17) the term psychosocial stressor 
was changed to the broader concept of stressor. Emotional reac-tions to physical stress, such as the Chernobyl reactor incident
(18)
or cardiac surgery(19) are well documented in literature and suggest

(18)
or cardiac surgery(19) are well documented in literature and suggest 
that psychosocial stressor as a criterion is too restrictive. Moreover, the concept of ‘psychosocial’ versus ‘physical’ stressors has led to confusion.
(20)
Obviously, the stressor and its effect are central to the AD diag-
nosis. The second major confound emanates from the fact that the DSM-IV presents no criteria or ‘guidelines’ to quantify stress-ors or to assess their effect or meaning for a particular individual at a given time. Furthermore, the assessment of stress is not linked by an algorithm to Axis IV—a statement of stress—during the previous year and so internal consistency or reinforcement within the diagnostic lexicon is not mandated (D. Schafer, personal com-munication, 1990). Mezzich et al .
(8) attempted to classify and 
quantify the psychosocial stressors in 13 speciﬁ  c domains: health,

quantify the psychosocial stressors in 13 speciﬁ  c domains: health, 
bereavement, love and marriage, parental, family stressors for children and adolescents, other familial relationships, otherrelationships outside the family, work, school, ﬁ  nancial, legal, 
housing, and miscellaneous. Such speciﬁ  city has not been deﬁ  ned 
in DSM-IV and the construct is vague and generic with minimal opportunity to achieve quantiﬁ  cation. Despland et al.
(21) observed 
that the type of stressor may indeed be of help in diagnosing AD. His study demonstrated that AD with depressed mood and mixed mood was associated with more marital problems than major depressive disorders. AD with anxiety could be distinguished from the major anxiety disorders by the quantity of family and marital problems.
(d) The time course

The time course and chronicity of both stressors and their conse-quent symptoms were left vague in DSM-IIIR and were not consis-tent with the clinical situation. The modiﬁ  cations introduced in 
DSM-IV , which differentiate between acute  and chronic  formsof AD, solved the problem of the 6-month limitation of the AD 
diagnosis in DSM-IIIR and is more in keeping with what is observed in the clinical situation. This change was validated by Despland et al.
(21) who observed that 16 per cent of patients with AD required 
treatment longer than 1 year—the mean exceeded the prior limita-tion of 6 months.
Other problems of deﬁ  nition
Even serious symptomatology (e.g. suicidal behaviour) that is not 
regarded as part of a major mental disorder requires treatment and a ‘diagnosis’ under which it can be placed, for example a V Code, ‘Phase of Life Problem’ , AD, acute stress response, etc. De Leo et al.
(22,23)  reported on AD and suicidality. Recent life events, which

(22,23)  reported on AD and suicidality. Recent life events, which 
would constitute an acute stress, were commonly found to corre-late with suicidal behaviour in a patient cohort which included those with AD.
(24) Spalletta et al .(25) observed the assessment of 
suicidal behaviour to be an important tool in the differentiation among major depression, dysthymia, and AD. AD patients were found to be among the most common recipients of a deliberate self-harm diagnosis, with the majority involving self-poisoning.
(26)
Thus deliberate self-harm is more common in AD patients,(26)
while the percentage of suicidal behaviour was found to be higher in AD patients with depressed mood.
(25)
The AD DSM-IV Work Group suggested that suicide and

(25)
The AD DSM-IV Work Group suggested that suicide and 
deliberate self-harm could be subtypes of AD. However, there were concerns that patients with other diagnoses, for example major affective disorder, borderline personality disorder, etc. and suicide behaviour, would be assigned the AD diagnosis since there was a speciﬁ  c placement for suicidal ideation and behaviour and that 
would be a predominant reason to use AD. The ﬁ  nal decision was 
to place the problem of suicidal symptomatology without a psychi-atric diagnosis in the DSM-IV F Code section for other problems ‘that may be a focus of clinical attention’ . Obviously a subthreshold diagnosis, AD, does not necessarily imply the presence of sub-threshold symptomatology!
Recognizing some of the limitations of the diagnosis includ-

ing the aforementioned lack of specificity of symptoms and the lack of clarity of the role of the stressor, the authors of a recent 
article proposed adding an additional ‘A-Criterion’ to the DSM 
IV diagnosis of AD. They studied 328 young conscripts diag-nosed by DSM IV with AD secondary to non-combat military stress. The diagnosis was closely associated with undisturbed psychosocial function outside of military life but with marked symptoms within military life.
(9) Thus, location-specific stress 
was associated with location-specific symptoms, a phenomenon that the authors found helpful in distinguishing AD fromother psychiatric diagnoses. Whether or not this finding would be consistent in non-military populations requires furtherevaluation.
‘Splitting’ and ‘lumping’ continue, for example, the subthreshold

‘Splitting’ and ‘lumping’ continue, for example, the subthreshold 
diagnosis of mixed anxiety-depressive disorder is a new category included in the DSM-IV . This disorder is very similar to AD with mixed mood; a boundary between the two is difﬁ  cult to demarcate. 
The main difference between the two diagnoses was the chronicity of the mixed anxiety-depressive disorder (as was noted in the mixed anxiety-depression ﬁ  eld trial).
(27) The change in criterion C for 
AD—allowing a chronic or recurrent disturbance—confounds the differentiation of these two subthreshold diagnoses. This uncer-tainty is further complicated by the question of treatment. Is this

719
an anxiety accompanied by depression, which should be treated 
with anxiolytics, such as benzodiazepines, or is this a depression accompanied by anxiety, which should be treated with an antide-pressant, such as a selective serotonin reuptake inhibitor (SSRI)? Furthermore, it is commonly viewed that the majority of patients with AD should be treated with psychotherapy or counselling as the initial approach.
Another potential mood disorder, subsyndromal symptomatic 
depression ( SSD ), has been suggested.
(28) It joins AD in the grey 
area of subthreshold diagnoses. However, there are two criticaldifferences between SSD and AD: SSD employs a symptom checklist, and is not associated with a stressor. By deﬁ  nition, SSD

is the simultaneous presence of any two or more symptoms of depression, persistent for most or all of the time for a duratioof at least 2 weeks, associated with social dysfunction, and occur-ring in patients who do not meet the criteria for minor depression (which also requires two symptoms), major depression, and/or dysthymia.
(28) In some cases, the SSD diagnosis is the same as
the DSM-IV diagnosis for minor depression, termed by theauthors ‘SSD with mood disturbance’ , and has to be documented as such. In other cases, the disorder is ‘SSD without mooddisturbance’ .
In a recent study, Casey et al . (2006) examined variables that

In a recent study, Casey et al . (2006) examined variables that 
might distinguish AD from other depressive episodes. The patients were screened for depression severity with the Beck Depression Inventory (BDI) and then interviewed with the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) which includes questions assessing the presence of AD. The authors were unable to ﬁ  nd any independent variables thatdistinguished AD from other depressive episodes, including the 
severity of the BDI score at the outset.
(29) Maercker et al. concep-
tualize AD as a stress response syndrome in which intrusions, avoidance of reminders, and failure to adapt are the centralprocesses and symptoms.
(30)
Age and medical comorbidity
In contrast with DSM-IIIR, DSM-IV has tried to accommodate the presence of comorbid medical illness. DSM-IIIR was regarded as ‘medical illness and age unfair’ (i.e. inadequate consideration of age and/or medical illness) (L. George, personal communication, 1981).

(31) T o enhance reliability and validity, there will need to be a 
psychiatric taxonomy that takes into account medical illness and symptomatology and developmental epochs (e.g. children and adolescents, adults, ‘young’ elderly, and ‘old’ elderly). (Actually, the original DSM did divide the AD by developmental epochs.) It is clear from the Western Psychiatric Institute studies that the symp-tom proﬁ  le for children and adolescents is very different from that 
for adults with regard to the entire spectrum of diagnoses. With regard to age, recent studies report AD patients to be signiﬁ  cantly 
younger compared with those with major psychiatric diagno sis.
(21,32)
Zarb’s study(33) suggests that in cognitively impaired elderly, using 
individual items of the Geriatric Depression Scale, AD could be dif-ferentiated from major depression. In addition, Despland et al.
(21)
showed that patients labelled AD with depressive or mixed symp-

(21)
toms included more women: a sex ratio resembling that seen in major depression or dysthymia. The future evolution of the DSM needs to consider the effect of developmental epochs, gender, and medical comorbidity on symptom proﬁ  les in the various diagnos-
tic categories.Grassi et al.
(34) investigated psychosomatic symptoms in patients 
with AD in a hospital setting in order to further characterize the diagnosis of AD in the medically ill. Results showed a considerable overlap between AD and abnormal illness behaviour including health anxiety, somatization, conversion symptoms, and demoral-ization among others. Only 13 out of 100 AD patients interviewed did not present with psychosomatic symptoms.
The Epidemiologic Catchment Area Study (ECA) did not include AD in its historic survey of patients in the population of ﬁ  ve major

The Epidemiologic Catchment Area Study (ECA) did not include AD in its historic survey of patients in the population of ﬁ  ve major 
settings in the United States. Most studies are of smaller or more discrete samples and have the problem of generalization. Andreasen and Wasek
(35) reported that 5 per cent of an inpatient and outpa-
tient sample at the university hospital and clinics in Iowa were labelled as having AD. Fabrega et al.
(36) reported that 2.3 per cent of 
a sample of patients presenting to a walk-in clinic (diagnostic and evaluation centre) met criteria for AD, with no other diagnoses on Axis I or Axis II; when patients with other Axis I diagnoses (i.e. Axis I and II comorbidities) were included, 20 per cent had the diagno-sis of AD. In general hospital inpatient psychiatric consultation populations, AD was diagnosed as 21.5 per cent, 18.5 per cent, and 11.5 per cent, respectively.
(37–39) D. Schafer (personal communica-

tion, 1990) noted that up to 70 per cent of children in the psychiatric setting may be given the diagnosis of AD in a variety of mental health care environments. Faulstich et al .
(40) reported the 
prevalence of AD for adolescent psychiatric inpatients. Andreasen and Wasek,
(35) utilizing a chart review, reported that more adoles-
cents than adults experienced acting out and behavioural symp-toms, but adults had signiﬁ  cantly more depressive symptomatology 
(87.2 per cent versus 63.8 per cent). Anxiety symptoms were frequent at all ages.
Mezzich and coworkers
(8) evaluated 64 symptoms currently 
present in three cohorts: subjects with speciﬁ  c diagnoses, those 
with AD, and those who were not ill. Vegetative, substance use, and characterological symptoms were greatest in the speciﬁ  c diagnosis

with AD, and those who were not ill. Vegetative, substance use, and characterological symptoms were greatest in the speciﬁ  c diagnosis 
group, intermediate in the AD group, and least in the group with non illness. The symptoms of mood and affect, general appearance, behaviour, disturbance in speech and thought pattern, and cogni-tive functioning had a similar distribution. The AD group was signiﬁ  cantly different from the non-illness group with regard to 
more ‘depressed mood’ and ‘low self-esteem’ ( p≤ 0.0001). The AD 
and non-illness groups had minimal pathology of thought content and perception. A positive response on the suicide indicators was obtained in 29 per cent of AD compared with 9 per cent of the non-illness group. The three cohorts did not differ on the frequency 
of Axis III disorders.
Associated features of adjustment disorder
Andreasen and Wasek(35) observed that in their AD cohorts

Andreasen and Wasek(35) observed that in their AD cohorts 
21.6 per cent of the adolescents’ fathers and 11.8 per cent of the adults’ fathers had problems with alcohol. Greenberg et al .
(41)
report more substance abuse in adults with diagnosed AD 
compared with all those with other diagnoses. Breslow et al .(42)
comparing patients with AD and other psychiatric diagnoses, 
observed that alcohol or substance use/abuse did not help todifferentiate between diagnostic groups. Thus, currently the higher rate of substance use does not serve as an incontrovertiblepredictive factor for the diagnosis of an AD diagnosis.4.6.4 adjustment disorders

SECTION 4  clinical syndromes of adult psychiatry 720
Aetiology—the role of stress
(a) Nature of the stressor
Andreasen and Wasek(35) described the differences between the 
chronicity of stressors found in adolescents compared with those in adults: present for a year or more, 59 per cent and 35 per cent; present for 3 months or less, 9 per cent and 39 per cent. Fabrega et al.
(36) reported that their AD group had greater registration of 
stressors compared with other diagnoses and the non-illness cohorts. Compared with other diagnoses and the non-illness patients, AD was over-represented in the ‘higher stress category’ . In their consultation cohort, Popkin et al.
(37) found that in 68.6 per 
cent of the cases the medical illness itself was judged to be the primary psychosocial stressor. Snyder and Strain
(39) observed that 
stressors as assessed on Axis IV were signiﬁ  cantly higher ( p = 
0.0001) for consultation patients with AD than for patients with other diagnostic disorders.

(b) Modiﬁ  ers of stress
Stress has been described as the aetiological agent for AD. 
Vulnerability to stress is another risk factor. Diverse variables and modiﬁ  ers are involved regarding who will experience AD following 
a stress. Cohen
(43) argues as follows:
1 acute stresses are different from chronic stresses in both psycho-
logical and physiological terms;
2 the meaning of the stress is affected by ‘modiﬁ  ers’ (e.g. ego 
strengths, support systems, prior mastery);
3 manifest and latent meanings of the stressor(s) may be associated 
with differential impact (e.g. loss of job may be a relief or a catastrophe).
An objectively overwhelming stress may have little impact on one

An objectively overwhelming stress may have little impact on one 
individual, whereas a minor stress could be regarded as cataclysmic by another. A recent minor stress superimposed on a previous underlying (major) stress that has no observable effect on its own 
may have a signiﬁ  cant additive impact (i.e. concatenation of events) 
(B. Hamburg, personal communication, 1990). Despland et al.
(21)
reported that stressors were present on Axis IV in 100 per cent of 
those assigned AD with depressed mood, while it was present in 83 per cent of those with major depression, 80 per cent of those with dysthymia, and 67 per cent of those with non-speciﬁ  c depression, 
which emphasizes the importance of stressors in the AD diagnosis.
Nine different types of AD are listed in DSM-IV .(1) As in DSM-III, 
AD is classiﬁ  ed in DSM-IIIR according to the predominant symptom

AD is classiﬁ  ed in DSM-IIIR according to the predominant symptom 
picture. In DSM-IV , AD has been reduced to six types that, again, are classiﬁ  ed according to their clinical features:
1 AD with depressed mood;2 AD with anxious mood;3 AD with mixed anxiety and depressed mood;
4 AD with disturbance of conduct;
5 AD with mixed disturbance of emotions and conduct; and6 AD not otherwise speciﬁ  ed.
In their study, Despland et al.
(21) suggested reducing the subtypes 
even further, demonstrating identical proﬁ  les for AD with depressed mood and AD with mixed mood, and proposing assimilation 
of mixed mood into the depressed mood category. Fifty-seven per cent of their sample was represented by these two groups; the remainder was accounted for by AD with ‘anxiety’ and ‘other’ categories.
Treatment
(a) Evidence regarding treatment

Treatment
In terms of randomized controlled trials (RCTs), a search of the Cochrane Database revealed only two RCTs on psychotherapeutic treatment of AD. Gonzales-Jaimes and Turnbull-Plaza (2002) showed that ‘mirror psychotherapy’ for patients suffering from AD with depressed mood secondary to a myocardial infarction was both an efficient and effective treatment. Mirror therapy is described as a type of therapy with psychocorporal, cognitive, and neurolinguistic components with a holistic focus. As part of the treatment, a mirror is used to encourage patient acceptance of his/her physical condition that resulted from past self-care behaviours. In this study, mirror therapy was compared to two other treat-ments, Gestalt psychotherapy or medical conversation in addition to a control group. Depressive symptoms improved in all treatment 
groups compared with the control group, but mirror therapy

groups compared with the control group, but mirror therapy 
appeared signiﬁ  cantly more effective than the other treatments in 
decreasing symptoms of AD at post-test evaluation.
(44)
In a second RCT, an ‘activating intervention’ was carried out for 
the treatment of AD which had resulted in occupational dysfunction. A total of 192 employees were randomized to receive either the intervention or care as usual.
(45) The intervention consisted of an

(45) The intervention consisted of an 
individual cognitive behavioural approach to a graded activity, similar to stress inoculation training. Goals of treatment empha-sized the acquisition of coping skills and the regaining of control. The treatment proved to be effective in decreasing sick leave dura-tion and shortening long-term absenteeism when compared to the control group; both intervention and control groups, however, showed similar amounts of symptom reduction. This study formed the basis for the Dutch Practice Guidelines for the treatment of AD in primary and occupational health care.
(46) These guidelines were 
prepared by a team of 21 occupational health physicians and one psychologist and subsequently reviewed and tested by 15 experts, including several psychiatrists and psychologists and 21 practicing occupational health physicians.
Though no other RCTs involving the psychotherapeutic treat-

ment of pure cohorts of patients with AD could be found, many RCTs exist that studied an array of depressive and anxiety disorders and that included AD in their cohorts. For example, a recent trial comparing brief dynamic therapy (BDT) with brief supportive therapy (BSP) in patients with minor depressive disorders, includ-ing AD, was found in the Cochrane Database. Though both thera-pies proved efﬁ  cacious in reducing symptoms, BDT was more 
effective as demonstrated in a 6 months follow-up.
(47)
Another therapeutic modality, eye movement desensitization 
and reprocessing (EMDR) has been recently studied in patients with AD.
(48) EMDR, a psychotherapeutic technique shown to be 
effective in the treatment of post-traumatic stress disorder, was carried out on nine patients suffering from AD. Results showed sig-niﬁ cant improvement in patients with anxious or mixed features

effective in the treatment of post-traumatic stress disorder, was carried out on nine patients suffering from AD. Results showed sig-niﬁ cant improvement in patients with anxious or mixed features 
but not in those with depressed mood. Additionally, those with ongoing stressors did not show improvement.

721
Hameed et al. in a retrospective chart review sought to determine 
if there was a difference in antidepressant efﬁ  cacy in the treatment 
of major depressive disorder versus AD in a primary care setting. Patients had been prescribed mostly SSRIs. DSM-IV symptoms, Patient Health Questionnaire-9 (PHQ-9) depression rating scale scores, and functional disability reports were systematically used to 
assess patients’ response. Results showed that neither depressed, nor AD patients demonstrated a difference in clinical response to 
any particular antidepressant. Patients with a diagnosis of AD, however, were twice as likely to respond to standard antidepressant treatment as depressed patients. This study suggests that antide-pressants are very effective in treating depression in the primary care setting and may be even more effective in the treatment for AD with depressed mood.
(49)
In another recent double-blind RCT, the efﬁ  cacies of etifoxine, a

(49)
In another recent double-blind RCT, the efﬁ  cacies of etifoxine, a 
non-benzodiazepine anxiolytic drug, and lorazepam, a benzodiaz-epine, were compared in the treatment of AD with anxiety in a pri-mary care setting.
(50) Efﬁ cacy was evaluated on days 7 and 28 using 
the Hamilton Rating Scale for Anxiety (HAM-A). The two drugs were found to be equivalent in anxiolytic efﬁ  cacy on day 28. 
However, more etifoxine recipients responded to the treatment. Moreover, 1 week after stopping treatment, fewer patients taking etifoxine experienced reb ound anxiety, compared to those given
lorazepam.
(50)
(a) Psychotherapy and counselling
Though brief therapeutic interventions are usually all that are needed, ongoing stressors or enduring character pathology that may make a patient vulnerable to stress intolerance may signal the need for lengthier treatments.
(51)
Treatment of AD initially focuses on psychotherapeutic and coun-

(51)
selling interventions to reduce the stressor, enhance the capacity to cope with a stressor that cannot be reduced or removed, and estab-lish a system of support to maximize adaptation. The patient needs to be made aware of the signiﬁ  cant dysfunction that the stressor has 
caused and consider strategies to manage the disability. Some stress-ors, for example taking on more responsibility than can be managed by the individual or putting oneself at risk (e.g. unprotected sex with an unknown partner), can be avoided or minimized. Other stressors may elicit an overreaction on the part of the patient (e.g. abandon-ment by a lover). The patient may attempt suicide or become reclu-sive, damaging his or her source of income. In this situation, the therapist would assist the patient to verbalize his or her disappointed feelings and rage rather than behaving destructively. The role of

verbalization in minimizing the discomfort of the stressor and 
enhancing coping cannot be overestimated. It is necessary to clarify and interpret the meaning/reality of the stressor for the patient. For example, if a mastectomy has devastated a patient’s feelings about her body and herself, it is mandatory to articulate that the patient is still a woman, capable of having a fulﬁ  lling relationship, including a 
sexual one and that recurrence of the cancer may not occur. Without the correction of distorti ons, the patient ’s pernicious fan-
tasies—‘all is lost’—may occur as sequelae to the stressor (i.e. the mastectomy) and intensify incapacitation at work and/or sex, as well as contribute to a profound disturbance of mood.
Counselling, psychotherapies, crisis intervention, family therapy, 
and group treatment are utilized to encourage the verbalization of fears, anxiety, rage, helplessness, and hopelessness to the stressors

and group treatment are utilized to encourage the verbalization of fears, anxiety, rage, helplessness, and hopelessness to the stressors 
imposed upon a patient. As mentioned above, the goal of treatment is to expose the concerns and conﬂ  icts that the patient is experienc-
ing, identify means to reduce the stressor(s), enhance the patient’s coping skills, clarify the patient’s perspective on the 
adversity, and enable the establishment of supporting relationships. The primary treatment for AD is talking.
(b) Psychopharmacotherapy
Should drugs be used in the treatment of AD? The pharmacological 
studies are not conclusive. The diagnostic dilemmas of the AD present sufﬁ  cient difﬁ  culty in and of themselves.
(52–54) It would be

(52–54) It would be 
preferred that cautious psychotropic drug administration be employed, to avoid subjecting the patient to the risk of unfavour-able medical drug-psychotrophic drug interaction(s). Psychotrophic drug treatment will not be necessary if the condition resolves. If it evolves into a major psychiatric illness then drug treatment needs to be actively entertained. And, for a refractory AD treatment with psychopharmacological agents should be considered. Small doses of antidepressants and anxiolytics may sometimes be appropriate for AD patients when dysphoria remains profound despite several sessions of psychological treatment.
Although formal psychotherapy is presently the treatment of 
choice, psychotherapy combined with benzodiazapines are utilized, especially for patients with severe life stress(es) and an unrelenting

choice, psychotherapy combined with benzodiazapines are utilized, especially for patients with severe life stress(es) and an unrelenting 
anxious component. Tricyclic antidepressants or buspirone were 
recommended in place of benzodiazapines for AD patients with current or past excessive alcohol use because of their greater risk of dependence.
(55) The use of antidepressants may assist some patients 
if their maladaptation is debilitating and the accompanying mood is pervasive, especially if a trial of psychotherapy has been shown to be ineffective.
Adults and adolescents
Andreasen and Hoenk(56) report that the long-term outcome of

Andreasen and Hoenk(56) report that the long-term outcome of 
AD has a good prognosis for adults, but that a majority of adolescentseventually have major psychiatric disorders. Follow-up at 5 years after original diagnosis of AD revealed that 71 per cent of adults were completely well, 8 per cent had an intervening problem, and 21 per cent had developed a major depressive disorder or alcohol ism. 
However, in adolescents at 5-year follow-up, only 44 per cent were without a psychiatric diagnosis, 13 per cent had an interven-ing psychiatric illness, and 43 per cent went on to develop major psychiatric morbidity (e.g. schizophrenia, schizoaffective disorders, major depression, bipolar disorder, substance abuse, and personality disorders). In contrast with the adults, the chronicity of the illness and the presence of behavioural symptoms in the adolescents were the strongest predictors for major psychopathology 5 years

after the initial AD diagnosis. The number and type of symptoms 
were less useful than the length of treatment and chronicity of symptoms as predictors of future outcome.
As Chess and Thomas
(57) have reported, it is important to note 
that AD with disturbance of conduct, regardless of age, has a more guarded outcome. In agreement with the ﬁ  ndings of Andreasen 
and Wasek,
(35) Chess and Thomas(57) emphasize that:
a signiﬁ  cant number [of AD adolescents] did not improve or even 
grew worse in adolescence and early adult life. It was not possible to predict the developmental course of the disorder in the early period after its ﬁ  rst identiﬁ  cation. Hence, we would suggest active appropriate 4.6.4 adjustment disorders

SECTION 4  clinical syndromes of adult psychiatry 722
therapeutic intervention in all cases but especially adolescents [and 
adequate follow-up].
Spalletta et al .(25) report that suicidal behaviour and deliberate 
self-harm are important predictors in the diagnosis of AD. As mentioned before, these are obviously not subthreshold symptoms; they can lead to the most dire consequence—death. This outcome, when reached, can be neither corrected nor resolved. These behav-iours mandate immediate and protective interventions. The diagnosis of AD may suggest that the patient has minor symptom-atology. Such erroneous assessment may be life-threatening. There needs to be a deﬁ  nite split from viewing a diagnosis as subthresh-
old, and therefore assuming the attendant symptoms to be sub-
threshold. It is similar to labelling a patient with hypochondriasis, which in some settings can inﬂ  uence a more casual physical assess-

ment, when such a patient could have serious physical morbidity concomitant with their hypochondriacal Axis I pathology.
Although most studies do point to a more benign prognosis for 
the AD, it is important to realize that the risk of serious morbidity and mortality still exists. Several recent studies investigating the association between suicide and AD underscore the importance of monitoring patients closely for suicidality, especially in younger populations. Portzky et al . conducted psychological autopsies on 
adolescents with AD who had committed suicide and found that suicidal thinking in these patients was brief and evolved rapidly without warning.
(60) A slightly different proﬁ  le was found in two

(60) A slightly different proﬁ  le was found in two 
other studies that looked at suicide attempters with a diagnosis of AD. These patients were more likely to have poor overall psychoso-cial functioning, prior psychiatric treatment, personality disorders, substance abuse histories and a current ‘mixed’ symptom proﬁ  le of 
depressed mood and behavioural disturbances.
(61,62)  A study of the 
neurochemical variables of AD patients of all ages who had attempted suicide revealed biologic correlates consistent with the more major psychiatric disorders. Attempters were found to have lower platelet MAO activity, higher MHPG activity, and higher 
cortisol levels than controls. Though these ﬁ  ndings differ from the 
lower MHPG and cortisol levels found in patients with major depression and suicidality, they are similar to ﬁ  ndings in other

lower MHPG and cortisol levels found in patients with major depression and suicidality, they are similar to ﬁ  ndings in other 
major stress-related conditions.
(63)
As mentioned earlier, the diagnosis of an AD may be in the early 
phase of an evolving disorder that has not yet developed to the extent that full-blown symptoms are evident to reach threshold for a major psychiatric disorder. If a patient continues to worsen, becomes more symptomatic, and does not respond to treatment, it is critical to review the diagnosis for the presence of a major disorder.
A recent report by Jones et al. (2002) looked at 10 years of read-
mission data for various psychiatric diagnoses including the AD. 
They found that admission diagnosis was a signiﬁ  cant predictor of 
readmission and that AD had the lowest readmission rates.
(58)
Furthermore, initial psychological recovery from an AD may in

(58)
Furthermore, initial psychological recovery from an AD may in 
large part be attributable to removal of the stressor. This was found to be the case in prisoners who developed AD after being placed in solitary conﬁ  nement and whose symptoms resolved shortly after 
their release.
(59)
The domains of diagnostic rigour and clinical utility seem at 
odds for AD. Studies that employ reliable and valid instruments (e.g. depression or anxiety rating scales, stress assessments, length of disability, treatment outcome, family patterns, etc.) would enhance more exact speciﬁ  cation of the parameters of the ADdiagnosis. Identiﬁ  cation of the time course, remission or evolution

to another diagnosis, and the evaluation of stressors (characteris-tics, duration, and the nature of adaptation to stress) would enhance the understanding of the aetiology, mechanisms, and mediators of a stress-response illness.
Studies with adequate symptom checklists rated independently 
from the establishment of the diagnosis would clarify the threshold between major and minor depression and anxiety, as well as guide an entry threshold to employ the AD diagnosis. Although the upper threshold is established by the speciﬁ  ed criteria for major syn-
dromes, the entry threshold between an AD and problem-level diagnoses and normality is undesignated with operational criteria. The careful examination of associated demographic and treatment outcome variables would also enable clinicians to describe more specifically the boundaries among subthreshold diagnoses, 
problem-level diagnosis, and normal behaviour. Associated

problem-level diagnosis, and normal behaviour. Associated 
features such as family history, biological correlates, treatment response, long-term course, and so forth, are all critical to establishing the validity of a diagnosis. The theory and practice of medicine have demonstrated the need for a comprehensive multi-dimensional formulation of all these physiological and functional variables to describe an illness and develop the most appropriate working diagnosis.
Subthreshold syndromes can encompass signiﬁ  cant psychopa-
thology that must not only be identiﬁ  ed but treated (e.g. suicidal 
ideation/behaviour). Cross-sectionally, AD may appear to be the incipient phase of an emerging major syndrome. Consequently, AD, despite its questionable reliability and validity, serves an important diagnostic function in the practice of psychiatry. Problem- and subthreshold-level diagnoses are critical to the func-tion of any medical discipline. Because this may be the initial phase,

or a mild form, of a dysfunction that is not yet fully developed, 
there is a need to describe the relationship of this incipient state to other potential diagnoses. This lack of speciﬁ  city and question-
able reliability and validity are the hallmark of interface disorders and subthreshold phenomena, whether they are in diabetes melli-tus, hypertension, or depression.
As mentioned earlier, the characteristics of a mental disorder 
vary over the life cycle, and this is clearly illustrated by the AD. Certain developmental epochs may be associated with a particular symptom proﬁ  le, as seen with acute myocardial infarction or 
appendicitis. The effect of the stressor may vary, and the assess-
ment of functioning must be ‘measured’ according to the demands

ment of functioning must be ‘measured’ according to the demands 
of the developmental stage (e.g. school [adolescents], work [adults], self-care and maintenance [elderly]). The symptom characteristics and functional assessment of other diagnoses may also vary along the developmental schema from birth to senescence; illnesses 
such as major depressive disorders, organic mental disorders, sexual 
dysfunctions, and eating disorders need to be ‘recast’ in another hierarchy to incorporate the stage of the life cycle extant at the time of the assessment, and symptom proﬁ  les adjusted accordingly. 
The normal variations across developmental epochs would make 
AD and the other psychiatric disorders more reliable and valid

AD and the other psychiatric disorders more reliable and valid 
across the life cycle. Similarly, there needs to be a consideration of a possible concomitant state of medical illness. The result would be a taxonomy tempered by the vicissitudes of development and medical illness.
A taxonomy which considers the development epoch and
the presence of medical illness would be more useful to child

723
psychiatrists, paediatricians, geriatricians, geriatric psychiatrists, 
and primary care specialists, who are often convinced that a patient does not conform with today’s psychiatry lexicon. A signiﬁ  cant 
number of their patients remain at the problem level of diagnoses 
with their somatic complaints as well. It is not uncommon for a fever of unknown origin to not be diagnosed, or for a chest pain to 
remain unspeciﬁ  ed. It is the art of medicine that makes it a profes-
sion, and a most difﬁ  cult one, at the interface of medicine and 
psychiatry, or at the interface of normality and pathology. Freud
(64)
has emphasized the difﬁ  culty of understanding normality and 
pathology in her assessments of childhood. This important advice 
would obtain across the life cycle and be an important challenge to the developers of the subthreshold diagnoses (e.g. AD) and the 
future evolution of the DSM.
Grassi, L., Mangelli, L., Fava, G.A., et al. (2007). Psychosomatic

Grassi, L., Mangelli, L., Fava, G.A., et al. (2007). Psychosomatic 
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64. Freud, A. (1968). Normality and pathology: assessment of childhood .
4.6.5 Bereavement
Beverley Raphael, Sally Wooding, 
and Julie Dunsmore
Bereavement is the complex set reactions that occurs with the death

Bereavement is the complex set reactions that occurs with the death 
of a loved one: the emotions of grief with yearning, angry protest, and sadness; the cognitive processes of understanding and making meaning of the ﬁ  nality and nature of death; and the social, cultural, 
spiritual, and religious contexts of adaptation. Grief may also result from other losses such as health, home, country, and safe worlds. There have been investigations into potential neurobiological sub-strates, without, as yet consensus about the explanatory model.
In ‘Mourning and Melancholia’ , Freud
(1) described the psycho-
logical processes of mourning which involved the gradual relin-quishment of bonds with the deceased, and how mourning differed from melancholia. Lindemann
(2) described the ‘Symptomatology

(2) described the ‘Symptomatology 
and Management of Acute Grief’ in his classic paper on his experi-ences assessing and treating the survivors of a nightclub ﬁ  re. 
Engel
(3) asked ‘Is Grief a Disease?’ , and concluded in the negative.
Bowlby’s work on attachment, separation, and loss(4–6) has been 
the most inﬂ  uential in informing research and clinical practice, 
with many studies of both adults and children utilizing such con-cepts. Early research focused chieﬂ  y on bereavement following the

725
death of a spouse, describing normal, high risk, and pathological 
patterns of grief.(7–9) There is also a number of excellent reviews of 
theory and research, including those of Stroebe’s group.(10,11)
Phenomenology of ‘normal grief’
Common phenomena of the grief experience of adults, identiﬁ  ed 
through many research studies,(12–14) relate to similar domains 
inﬂ uenced by developmental trajectories, through childhood and 
adolescence. Adult studies indicate consistent patterns: numbness, disbelief; yearning, angry protest, and ‘searching’ behaviours repre-senting separation distress; and sadness with reviewing of memo-ries of the lost relationship, with a range of associated emotions; progressive acceptance of the death and changed circumstances, sometimes referred to as resolution.
Bonanno
(14) has shown that resilient trajectories, deﬁ  ned by low 
overall distress, are common. Other transient phenomena described by clinicians working with bereaved people

Bonanno
(15) include: identiﬁ  catory 
symptoms, reﬂ  ecting the deceased’s illness; a sense of the deceased’s 
ongoing at presence, at times as though seeing the face, hearing the voice, or feeling the touch of the dead person. ‘Y earning’ is con-sidered to be the most pathognomic of these grief phenomena, which usually settle over the ﬁ  rst year, but may continue, triggered 
by anniversaries, or speciﬁ  c memories. Older people who have had 
a long relationship with a spouse may continue this relationship in their minds for the comfort of ‘talking’ with the person, and a need for the ongoing closeness.
(16)
Recent research(17) has modelled sequential peaks of the reactive

(16)
Recent research(17) has modelled sequential peaks of the reactive 
phenomena: disbelief, yearning, anger, and depression, which bereaved people more usually describe as sadness. Grief may be a precipitant of depression in those with pre-existing or bereavement-related vulnerabilities and the differentiation of normal and more pathological forms of grief from depression is important clinically.
(15,18) Intense grief and the peaks of distress identiﬁ  ed 
above do not usually continue beyond the ﬁ  rst 4–6 months.(12,13)
Continuing ‘acute’ grief beyond this time suggests the possibility of 
pathological response, as do other risk indicators, although some phenomena may continue intermittently for many years. Comparative studies have demonstrated that the intensity of adult grief is likely to be greatest for the death of a child, then spouse, or partner, then parent.
(12,19)
Neurobiology of bereavement

(12,19)
Recent research has examined the neurobiology of grief through studies using functional magnetic resonance imaging of grief 
(20)
and brain activity in womºen grieving the break-up of a romantic relationship.
(21) Workers have attempted to develop a theoretical 
model based on a wide range of relevant data, encompassing a ‘neurobiopsychosocial’ framework for sadness and loss.
(22) Stress 
hormones(23) and psychoimmune function is a further area of 
research. A comprehensive model integrating the relevant research ﬁ ndings is yet to be established.
Risk and protective factors inﬂ  uencing 
course and outcome
Pre-existing vulnerabilities  that may influence the course and

outcome have been reviewed alongside other risk factors.(24)These include personality vulnerabilities related to relationship styles such as avoidant and insecure attachments. Genetic factors do not appear to have been directly studied, but it is likely that the short allele of the serotonin gene promoter polymorphism of 5HTTLPR which inﬂ  uences response to adversity may contribute, 
through gene–environment interactions.
(25) Prior loss and adverse 
experiences may add vulnerability, for instance multiple losses faced by indigenous peoples, with loss of culture, land, and loved ones, with multiple premature deaths and separations.
(26)

(26)
Separation anxiety in childhood, as well as pre-existing psychiatric disorder, family psychiatric disorder, and substance abuse may add to vulnerability. Successful negotiation of earlier losses, mature defence styles, and optimism may be protective.
The nature of the lost relationship  has been identiﬁ  ed in a number 
of studies as being a signiﬁ  cant factor.
(15,27)  The special relationship 
between parent and child is associated with greater vulnerabilities, including increased risk of psychiatric hospitalization and even death by suicide. Patterns of distress differ by gender with stillbirth, neonatal deaths, and sudden infant death syndromes, perhaps suggesting different attachment patterns.
(28) The death of an ado-

lescent child is not infrequently by accident, suicide, or risk-taking with illicit drugs, bringing the extra complexities of adaptation for the grieving parents.
A great deal of research has explored the grief associated with the 
death of a partner or spouse both young and old. High levels of dependence and ambivalence have been shown to complicate grief and to be associated with more difﬁ  cult bereavement,
(15,27)  and 
prolonged or complicated grief may be more likely.
Family members may have different relationships with the 
deceased, and thus varying patterns and trajectories of grief, which may cloud the recognition of children’s and others needs.
Adults’ loss of an older parent appears to be the least distressing, 
although there is still sadness plus the recognition of one’s own mortality. Here, as at any age, intense fantasies of reunion with the deceased may indicate risk of suicide, especially for older widowed men.

Circumstances of the death  may inﬂ  uence outcome. When dying 
isprolonged , as in the later stages of a terminal illness, the dying 
person may experience grief over his or her own life, and the loved ones who will be lost to him, alongside the anticipatory grieving 
of family members. While palliative care systems may provide 
bereavement programmes, families have complex dynamics, and may require family focused interventions.
(29)
Sudden unexpected  deaths bring an extra level of emotional 
shock,(30) especially if also untimely as with children’s death. When 
violent death occurs, as with homicide or the mass violence of terrorism or war, those bereaved may experience a complex mix-ture of traumatic stress reactions and grief reactions, sometimes called traumatic grief.
(31) The speciﬁ  c issues facing those bereaved 
by violent deaths of loved ones have been reported in a recent volume by Rynearson,
(32) which deals with homicide, terrorism,

(32) which deals with homicide, terrorism, 
and other violent deaths. The prolonged and difﬁ  cult grief in such 
circumstances is highlighted by findings from September 11, Oklahoma, and Bali bombings.
When people are missing , believed dead, the uncertainty, other 
stressors including complex legal and evidentiary processes(e.g. Disaster Victim Identiﬁ  cation requirements), may lead to 
alternating hope and dread. When there are no remains, it will be more difﬁ  cult for those bereaved to accept the reality of the death. 4.6.5 bereavement

SECTION 4  clinical syndromes of adult psychiatry 726
Seeing and ‘saying goodbye’ to the dead person, have been shown 
to help those bereaved in disasters. If remains are much disﬁ  gured, 
as with burns, it is important that those bereaved are supported in their choice about this.
Social support , particularly the perceptions of the supportiveness 
of family and social network are likely to be protective and assist the bereaved psychologically,
(33) while perceptions of unhelpful-
ness may be associated with more negative outcomes.(9) Cultural 
requirements for social support may differ, as may the delineation of the period of mourning, the roles of the bereaved, and associated spiritual and religious needs.
(34)
Multiple other adversities  may occur, either coincidentally or as a 
consequence of the circumstances and the loss of the person, for instance ﬁ  nancial difﬁ  culties, loss of resources, changed status, loss

consequence of the circumstances and the loss of the person, for instance ﬁ  nancial difﬁ  culties, loss of resources, changed status, loss 
of meaning and identity, or other profound stressors of illness, injury, or other bereavements. Such additional stressors may increase vulnerability.
(15)
In terms of Prolonged Grief Disorder  (previously known as 
complicated grief disorder, and initially traumatic grief) Prigerson et al.
(35) have carried out extensive research to reﬁ  ne this syndrome. 
Bringing together the views of international researchers, they have developed consensus criteria for a distinct psychiatric disorder to be considered for inclusion in DSM-V . This deﬁ  nition requires that 
the reaction to loss encompasses one of three symptoms of separa-tion distress (e.g. yearning) and a minimum of ﬁ  ve from a total of

the reaction to loss encompasses one of three symptoms of separa-tion distress (e.g. yearning) and a minimum of ﬁ  ve from a total of 
nine other symptoms, experienced at least daily, to a distressing or disruptive level. These include: shock; emotional numbing; avoidance of the reality of the loss; difﬁ  culty accepting the loss; 
feelings of meaninglessness; difﬁ  culty moving on with life; bitter-
ness over the loss; mistrust; and a diminished sense of self. Such symptoms would need to last at least 6 months, and be associated with signiﬁ  cant levels of functional impairment. These ﬁ  ndings ﬁ  t 
well with earlier research identifying more chronic patterns of 
grief.
(12,13)
Physical and mental health consequences 
of bereavement
A recent valuable review(36) outlines the evidence of increased 
mortality  for bereaved spouses, particularly males which is most 
pronounced in the ﬁ  rst 6 months, and includes a range of condi-

tions such as heart disease, leading to death from ‘a broken heart’ . It is also more pronounced for those younger. Death of a child is associated with even greater mortality risk, particularly for mothers. Suicide is one of the heightened risks, especially for mothers and older males.
Physical health  impairments are also found,
(36) with a variety of 
physical symptoms as well as greater use of medical services, and medications. Further research is needed to clarify the nature of any increased rate of speciﬁ  c diseases. Changed health behaviours, the 
impact of loss of a health supporting partner, functional or social changes, or shared environments of risk may contribute.
With regard to mental health  there may be an increased level

With regard to mental health  there may be an increased level 
of anxiety and depressive symptoms. There may be a heightened risk for some bereaved individuals for exacerbations of pre-existing conditions, or the precipitation of new illnesses, including Post-Traumatic Stress Disorder when there is a violent death.
(32) Other 
anxiety disorders, major depression, substance use disorder, and bipolar disorder may be precipitated by bereavement. Complicated or prolonged grief disorder may also represent a psychiatric 
consequence.
(35)
Assessment and management
Most bereaved people do not require counselling so assessment must be a basis for intervention. Assessment should be simple, synchronous with need, and do no harm, addressing the death and its circumstances, the relationship, and the bereaved’s experience since, including social support.

(31) A more structured format, 
potentially including grief measures,(37) can clarify the presence of 
PTSD, Depression or Prolonged Grief, or other health needs, including physical health changes or problems, establishing the basis for intervention.
Initial management of acutely bereaved persons requires empathic, 
compassionate support; and responding to any acute needs in ways that are protective of their mental health, recognizing the ‘roller-coaster’ of emotions that may occur, and facilitating natural resil-ience. Concepts of Psychological First Aid are also valuable in the immediate period after the death.
(38) Dealing with concerns about 
the deceased’s suffering, and support to view the dead person’s remains should the bereaved choose to, are likely to be helpful.
Most evidence-based interventions focus on psychotherapeutic 
methods, ranging from preventive counselling of those with dem-onstrated heightened risk
(39) to self-help guided interventions,(40)

interpersonal psychotherapy modiﬁ  cations for traumatic grief,(41)
integrated cognitive behaviour therapy models,(42) or psychody-
namically informed models(43) and web-based treatments.(44)
Counselling models(45) and psychoeducation have also focused on 
those bereaved through speciﬁ  c deaths such as those of infants.(46)
Other models deal with grief work and tasks,(47) as well as speciﬁ  c 
treatment for morbidity of complicated grief(48) and depressive 
or anxiety disorders including the use of pharmacotherapy for such conditions when indicated.
(49) Rynearson’s(32) work with 
‘restorative retelling’ following violent deaths emphasizes the narrative story which is central to much bereavement counselling and testimony.
A practical approach to assessment and counselling may be initi-

ated with some gentle queries, such as ‘Can you tell me a little about your loss?’ , ‘What happened with ‘John’s’ death?’ , ‘Can you tell me about ‘John’ and your relationship?’ , ‘What’s been happening since?’
If there is: intense continuing distress; circumstances of death 
which are untimely or traumatic; a complex relationship with the deceased; disruption of family functioning which is impacting on the needs of children; inadequacies of social support; ‘unresolved’ earlier losses; multiple additional stressors, the bereaved may be at heightened risk of adverse outcomes. Preventive counselling, which 
facilitates grieving, is attuned to the bereaved person’s readiness, 
vulnerabilities, and strengths, and helps them to tell the story of their experiences and the person they have lost, is likely to improve outcomes.
(39)
If assessment indicates that psychiatric disorders have arisen, for

(39)
If assessment indicates that psychiatric disorders have arisen, for 
instance depression, post-traumatic stress disorder, anxiety, or substance use disorders, these conditions should be managed appropriately alongside counselling for the bereavement should this be required. The use of antidepressants or other medication is not indicated for bereavement itself but may be appropriate for such complications.
(49) Monitoring for suicide risk should accom-
pany clinical management.

727
Prolonged or complicated grief may beneﬁ  t from cognitive 
behaviour therapy interventions, as well as relevant rehabilitation. Those who are both traumatized and bereaved may need the traumatic stress issues, to be dealt with ﬁ  rst, and facilitation of 
grieving following this.
(43)
There is a need for more comprehensive research and evaluation 
of prevention, early intervention and treatment modalities, and their appropriate provision, to individuals, families, or groups.
(50)
Culturally appropriate models of support and intervention also need to be further developed. Many bereaved people present ﬁ  rst 
within primary care settings, and to their general practitioners who will need the skills and knowledge to deal with their distress, assess their needs, counsel them as appropriate, and refer when necessary.
Much support also comes from community and non-government 
agencies including bereavement focused groups for speciﬁ  c losses

agencies including bereavement focused groups for speciﬁ  c losses 
or for grief generally, and from specialized services in public or private mental health sectors.
T elling the bereaved person how to grieve, that they should 
‘forget about the past’ , that ‘time heals all’ , is usually perceived as 
unhelpful. Treating grief as a disease, for example antidepressant 
medication for normal sadness, is seen by many bereaved people as interfering with their capacity to grieve for their loved one.
Counselling bereaved people requires hopeful, compassionate

Counselling bereaved people requires hopeful, compassionate 
psychotherapeutic intervention which recognizes the human suf-fering involved, validates the person’s strengths, and respects their spiritual needs. Loss is a central issue for all of us, both our fears of it, and its reality. Counselling requires those involved to recognize their own sensitivities in this regard, and to assist the ‘journey’ of those affected in dealing with their loss. Most people grieve, remem-ber with love those whom they have lost, and continue to love, and love anew.
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psychological trauma and PTSD  (2nd edn). The Guilford Press, 
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SECTION 4  clinical syndromes of adult psychiatry 728
32. Rynearson, E.K. (ed.) (2006). Violent death: resilience and intervention 
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33. Vanderwerker, L.C. and Prigerson, H.G. (2004). Social support and 
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complicated grief: a randomized controlled trial. The Journal of the 
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4.7
4.7.1 Generalized anxiety disorders
Stella Bitran, David H. Barlow, 
and David A. Spiegel
Anxious apprehension and overconcern are common to many 
anxiety and mood disorders. Prior to 1980 in the American DSM diagnostic system, and 1992 in the international ICD system, individuals who experienced those symptoms in the absence of a realistic focus of concern were classiﬁ  ed as having an ‘anxiety 
neurosis’ (DSM-II) or ‘anxiety state’ (ICD-9). In DSM-III, panic disorder was split off from that classiﬁ  cation, and the residual cat-
egory was renamed generalized anxiety disorder ( GAD ). A similar 
nomenclature was adopted in ICD-10.
Since its inception, GAD as a nosological entity has been trou-
bled by problems of poor reliability and high comorbidity.
(1) Those

(1) Those 
concerns have prompted several revisions of the DSM criteria and also have raised more basic questions regarding the validity of GAD as a disorder distinct from other anxiety and mood states. The question of what is the nature of GAD is still being debated and it remains one of the least reliably diagnosed anxiety or mood disorders.
(2) This diagnostic unreliability has led to various sugges-
tions for revisions to the diagnostic criteria and criticisms of the current deﬁ  nition of GAD.Clinical features
Individuals with GAD experience persistent anxiety and worry that 
is out of proportion to actual events or circumstances. Typically, the anxiety and worry involve minor or everyday matters, such as work, ﬁ  nances, relationships, the health or safety of loved ones, and

routine tasks. Often, the focus of worry shifts from one concern to another. Although people with GAD do not always consider their worries to be unrealistic or excessive, they do ﬁ  nd them difﬁ  cult to 
control. Consequently, the worries often interfere with concentra-tion and performance.
Associated with the anxiety and worry, individuals with GAD 
have a variety of cognitive and somatic symptoms, including trem-bling, feeling shaky, aching in the back and shoulders, tension headaches, chest tightness, restlessness, exaggerated startle, irritab ility, 
insomnia, fatigue, dry mouth, sweating, urinary frequency, trouble 
swallowing, nausea, and diarrhoea. In addition, GAD may be 
accompanied by other conditions typically associated with stress, such as irritable bowel syndrome or atypical chest pain.
Diagnosis
(a) DSM criteria
In DSM-III, GAD was essentially a residual category for individuals

Diagnosis
In DSM-III, GAD was essentially a residual category for individuals 
with somatic symptoms of anxiety who did not meet diagnostic criteria for another, more speciﬁ  c, anxiety disorder. Diagnosis 
required the presence, for at least a month, of symptoms from three of four symptom clusters: motor tension, autonomic hyperactivity, apprehensive expectation, and vigilance and scanning. Unfortunately, clinicians had difﬁ  culty applying those criteria. 
In addition, its diagnosis depended on the application of the crite-ria for other diagnoses since GAD was not diagnosed if another anxiety disorder was present.
In DSM-III-R, apprehensive expectation was removed from the 
diagnostic symptom clusters, was redeﬁ  ned as unrealistic or exces-
sive anxiety and worry about two or more life circumstances, and 
was made the essential feature of GAD. In addition, the duration 
criterion was changed from 1 to 6 months, and the hierarchical

criterion was changed from 1 to 6 months, and the hierarchical 
exclusion rule was dropped, allowing GAD to be diagnosed in addition to other disorders.Contents
 4.7.1 Generalized anxiety disorders
phobias
  4.7.3 Panic disorder and agoraphobia

SECTION 4  clinical syndromes of adult psychiatry 730
Despite those changes, the diagnostic reliability of GAD remained 
essentially unchanged.(1) Investigations revealed that the new worry 
criterion was problematic. Interviewers commonly disagreed as to whether two distinct spheres of worry were present, whether the worry was unrealistic or excessive, or whether the focus of the worry could be construed to be part of the symptomatology of another disorder. Moreover, studies indicated that patients with GAD did not differ substantially from control subjects in the content of their worries.
(3,4) The main difference between patients 
and controls was that the former experienced their worrying to be uncontrollable while the latter did not.
Based on those and other ﬁ  ndings, the GAD criteria were revised

Based on those and other ﬁ  ndings, the GAD criteria were revised 
again in DSM-IV . The ‘unrealistic’ descriptor and the requirement for anxiety or worry to involve at least two spheres of life circum-stances were deleted, and a new criterion was added that the worry must be experienced as difﬁ  cult to control. In addition, the associ-
ated symptom criterion was modiﬁ  ed to require only three of 
six symptoms from the previous motor tension and vigilance and scanning clusters (Table 4.7.1.1). For additional information about the evolution of the DSM criteria for GAD, see Barlow or Wincze.
(5)
(b) ICD-10 criteria

(5)
Like DSM-IV , ICD-10 requires a period of 6 months of generalized anxiety and worry accompanied by certain somatic symptoms (Table 4.7.1.2). The 6 months of ‘prominent’ tension and worry needs to be accompanied by at least 4 of 22 associated symptoms. The ICD-10 differs from DSM-IV in that it does not require that worry be ‘uncontrollable’ , that the symptoms of GAD occur exclusively outside the context of a mood disorder, or that they meet a ‘clinical signiﬁ  cance’ criterion.
(c) Differential diagnosis
Everyone experiences anxiety and worry sometimes, and some 
people describe themselves as born worriers. GAD differs from these non-pathological anxiety experiences in that it is both persis-tent and severe enough to cause signiﬁ  cant distress or interference. 
Typically also, the worries are more pervasive and difﬁ  cult to 
control than normal worries and are associated with physical 
symptoms of anxiety and tension.

A number of general medical conditions can present with signs 
and symptoms resembling GAD (Table 4.7.1.3). In addition, 
substances such as caffeine, alcohol, other drugs of abuse, toxins, 
and some medications (Table 4.7.1.4) can cause anxiety-likeTable 4.7.1.1  DSM-IV inclusion criteria for GAD
(a)  Excessive anxiety and worry, occurring more days than not for at least 
6 months, about a number of events or activities
(b) The person ﬁ  nds it difﬁ  cult to control the worry(c)  The anxiety and worry are accompanied by at least three of the following 
six symptoms (one in children): restlessness or feeling keyed up or on 
edge; being easily fatigued; difﬁ  culty concentrating or mind going blank; 
irritability; muscle tension; sleep disturbance
(d)  The anxiety, worry or physical symptoms cause signiﬁ  cant distress or

(d)  The anxiety, worry or physical symptoms cause signiﬁ  cant distress or 
functional impairment
(American Psychiatric Association (2000), Diagnostic and statistical manual of mental 
disorders  (4th edn, text revision). APA, Washington, DC)Table 4.7.1.2  ICD-10 inclusion criteria for GAD
(a)  At least 6 months of prominent tension, worry, and feelings of 
apprehension about everyday events and problems
(b)  At least four of the following 22 symptoms must be present, at least one 
of which must be from the autonomic arousal cluster
Autonomic arousal symptoms: palpitations or pounding heart or 
  accelerated heart rate; sweating; trembling or shaking; dry mouth (not due 
to medication or dehydration)
Symptoms involving the chest and abdomen: difﬁ  culty in breathing; feeling 
 of choking; chest pain or discomfort; nausea or abdominal distress
Symptoms involving mental state: feeling dizzy, unsteady, faint or

of choking; chest pain or discomfort; nausea or abdominal distress
Symptoms involving mental state: feeling dizzy, unsteady, faint or 
  lightheaded; derealization or depersonalization; fear of losing control, ‘going 
crazy’, or passing out; fear of dying
General symptoms: hot ﬂ  ushes or cold chills; numbness or tingling 
 sensations
Symptoms of tension: muscle tension or aches and pains; restlessness and 
  inability to relax; feeling keyed up, or on edge, or mentally tense; a sensation 
of a lump in the throat, or difﬁ  culty in swallowing
Other non-speciﬁ  c symptoms: exaggerated response to minor surprises 
  or being startled; difﬁ  culty in concentrating, or mind ‘going blank’ because 
of worrying or anxiety; persistent irritability; difﬁ  culty getting to sleep because of worrying
(World Health Organization (2004), International statistical classiﬁ  cation of diseases and 
health related problems  (2nd edn). WHO, Geneva, Switzerland)

Table 4.7.1.3  General medical conditions that can cause symptoms 
resembling anxiety
Cardiac conditions: arrhythmias, coronary insufﬁ  ciency, mitral valve prolapse, 
 heart failure
Endocrine conditions: hyperthyroidism, hypoparathyroidism, hypoglycaemiaNeurological conditions: temporal lobe epilepsy, vestibular nerve diseaseRespiratory conditions: asthma, hypoxia, hyperventilation, obstructive 
 lung disease, pulmonary embolism
Other conditions: porphyria, carcinoid tumour, systemic lupus erythemacosus, 
 pellagra
Table 4.7.1.4  Medications that can cause symptoms resembling 
anxiety
Psychotropics: antidepressants, neuroleptics (akathisia), sedative hypnotics 
 (withdrawal syndrome), disulﬁ  ram

pellagra
anxiety
Respiratory drugs: B-adrenergic stimulants, bronchodilatorsCardiovascular drugs: antiarrhythmics, antihypertensivesNeurological disorder medications: anticonvulsants, anticholinergic agents, 
 
L-dopa
Anaesthetic drugs: pre-anaesthetics, general anaesthetics (post-anaesthetic 
 syndrome)
Other drugs: thyroid hormone, antibiotics, non-steroidal anti-inﬂ  ammatory 
 drugs, anticancer drugs

731
symptoms either as a direct effect or as part of a withdrawal syn-
drome. These causes may be established on the basis of a medical and substance use history, physical examination, or laboratory tests.
GAD is distinguished from other psychiatric disorders, in part, 
by the focus of the anxiety and worry, which is not limited to a feature of another disorder. For example, the worry is not only 
about the possible occurrence or implications of panic attacks (as in panic disorder), or about negative evaluations by others (social 
phobia), gaining weight (anorexia nervosa), or having a serious ill-ness (hypochondriasis). In obsessive–compulsive disorder, the anx-iety and worry are associated with intrusive thoughts, images, or impulses that are distressing.
Generalized anxiety commonly occurs in depression, and GAD

Generalized anxiety commonly occurs in depression, and GAD 
and depression also share associated symptoms such as sleep disturbance, fatigue, restlessness, and poor concentration. When the associated symptoms could ﬁ  t with either disorder, the distinc-
tion is made on the basis of the presence and time course of depressed mood relative to anxiety. In DSM-IV , GAD is not diag-nosed if its features occur exclusively during a mood disorder.
Prevalence estimates of GAD vary considerably with the diagnostic criteria used. One large-scale study found a 12-month prevalence rate of 2.07 per cent and a lifetime prevalence rate to be 4.1 per cent.
(6)
Socio-demographic factors associated with increased risk for GAD included being female, middle-aged, and with low income. However, being African American, Asian, or Hispanic was associ-ated with a decreased risk.
(7)
The National Comorbidity Study Replication (NCS-R), which used

(7)
The National Comorbidity Study Replication (NCS-R), which used 
DSM-IV criteria and included structured interviews of over 9000 individuals in the United States, found a 12-month prevalence of GAD of 3.1 per cent and a lifetime prevalence rate at 5.7 per cent.
(8,9) 
Lifetime prevalence rates were lowest among 18- to 29-year-olds (4.1 per cent) and those 60 or older (3.65 per cent), with the highest rates found among 45- to 59-year-olds (7.7 per cent).
(e) Comorbidity
GAD usually coexists with other anxiety and mood disorders. One large-scale study found that 68 per cent of individuals with a principal diagnosis of GAD met criteria for another Axis I disorder (Table 4.7.1.5).
(10) The most frequently comorbid disorders were MDD, social phobia, or panic disorder with or without agoraphobia.

(10) The most frequently comorbid disorders were MDD, social phobia, or panic disorder with or without agoraphobia. 
Ninety-two per cent of individuals from this study with a principal diagnosis of GAD met criteria for another lifetime disorder, with 64 per cent meeting criteria for MDD. Similarly, in the major epidemiological surveys, nearly two-thirds of individuals with GAD had additional DSM Axis I diagnoses.
(11) Most common among these 
were speciﬁ  c (21–59 per cent) and social (16–59 per cent) phobias, 
followed by panic disorder (3–27 per cent) and depression (8–39 per cent). In addition, GAD was found to be approximately twice as common among women as men. There is less information about the prevalence of personality disorders among patients with GAD.
(f) Is GAD a valid disorder?
The ﬁ  ndings of only fair diagnostic reliability and high comorbidity

The ﬁ  ndings of only fair diagnostic reliability and high comorbidity 
for GAD have been interpreted as indicating poor discriminant validity of the disorder, suggesting that differentiating GAD from other anxiety and mood disorders may be artifactual. In considering those arguments, it is important to distinguish the diagnostic crite-ria sets speciﬁ  ed in the DSM and ICD classiﬁ  cation systems from 
the clinical syndromes they are intended to identify. Low discrimi-nant validity for a disorder may be due to problems with the former rather than the latter. T o establish the construct validity of a syn-drome, one must demonstrate that it has a consistent set of features, the pattern of which separates it from other related syndromes. One approach to doing that is to compare the proﬁ  les of patients with 
different diagnoses across various illness dimensions.
In one such study, data from patients who took part in the DSM-IV

In one such study, data from patients who took part in the DSM-IV 
mixed anxiety-depression ﬁ  eld trial were examined.
(12) Using 
factor analyses of patients’ scores on 73 items from the Hamilton anxiety and depression rating scales, four clusters were identiﬁ  ed 
that corresponded to the dimensions of anxiety, depression, physi-ological arousal, and general negative affect (containing items that loaded on both the anxiety and depression factors). Patients with a principal diagnosis of GAD had a unique proﬁ  le (high on negative 
affect and anxiety, low on physiological arousal and depression) that distinguished them from individuals with panic disorder, major depression, anxiety or depressive disorder not otherwise speciﬁ  ed, or no mental disorder.
A subsequent study, using an anxiety clinic sample and an 
expanded array of measures, yielded similar results.
(13) In this case,

(13) In this case, 
ﬁ ve primary factors (corresponding to panic, agoraphobia, social 
anxiety, obsessions/compulsions, and general anxiety) and a higher order factor (negative affect) were identiﬁ  ed. Again, patients with 
GAD had a unique factor proﬁ  le.
The ﬁ  ndings from the preceding studies were replicated and 
extended in an independent sample of patients.
(14) As in the earlier 
studies, GAD was found to be distinct from other anxiety syndromes and depression, although it had the highest degree of overlap with other syndromes, especially depression. In addition, GAD was strongly associated with the non-speciﬁ  c dimension of negative 
affect, which is common to anxiety and depression. The authors suggest that GAD may represent a ‘basic emotional disorder’ , because it consists of features that are present to varying degrees in all anxiety and mood disorders.

Finally, all three of the preceding studies (and a variety of others, 
e.g. Barlow et al.
(15) support the differentiation of symptoms of 
autonomic arousal, which are characteristic of panic attacks, from somatic symptoms related to central nervous system tension, which form the DSM-IV-associated symptom cluster of GAD.Table 4.7.1.5  Prevalence of comorbid disorders in 279 patients 
with GAD
Any additional lifetime disorder 96%
Any anxiety/mood 94%Any anxiety disorder 85%Any mood disorder 74%
Panic disorder with/or without agoraphobia 47%Social phobia 46%Speciﬁ  c phobia 22%Mood disordersMajor depressive disorder 67%Dysthymia 11%
Copyright © (2009) by the American Psychological Association. Reproduced with permission. 
T.A. Brown, L.A. Campbell, C. L. Lehman, et al (2001) Current and lifetime comorbidity of 
the DSM-IV anxiety and mood disorders in a large clinical sample, Journal of abnormal

the DSM-IV anxiety and mood disorders in a large clinical sample, Journal of abnormal 
psychology,  110, 585-99. The use of APA information does not imply endorsement by APA.4.7.1 generalized anxiety disorders

SECTION 4  clinical syndromes of adult psychiatry 732
(g) Aetiology
Findings from genetics, neurobiology, and psychology infer a mul-
tifactorial aetiology for GAD, which has been organized into a tri-
ple vulnerabilities model.(16,17)This model suggests that anxiety 
disorders result from the combination of a generalized biological 
vulnerability, a general psychological vulnerability, and a speciﬁ  c 
psychological vulnerability.
(i) Generalized biological vulnerability
Genetic contributions. Several studies investigating genetic 
vulnerabilities for mental disorders have supported the notion that 
a shared vulnerability underlies anxiety disorders.(18) It was shown 
through a meta-analysis of genetic epidemiological studies that 
many anxiety disorders (including GAD, panic disorder, phobias, 
and OCD) aggregate in families and that genetics has the most 
inﬂ uence when examining familial risk.(19) In a family study that

inﬂ uence when examining familial risk.(19) In a family study that 
used DSM-III criteria, GAD (but not other anxiety disorders) was 
ﬁ ve times more prevalent (19.5 per cent versus 3.5 per cent) among 
ﬁ rst-degree relatives of patients with GAD than among relatives of 
controls.(20) However, two twin studies using the same criter ia found
concordance rates for GAD were no higher among monozygotic 
than dizygotic twins.(21) Two subsequent studies that used DSM-
III-R criteria found a shared heritability for GAD and mood dis-
orders.(22) At present, it appears that genetic factors play a modest 
role in the aetiology of GAD, and one that is more closely related to 
vulnerability for depression than for other anxiety disorders.
Neurobiological mechanisms. A variety of neuroanatomical, 
neurochemical, neuroendocrine, and neurophysiological systems

neurochemical, neuroendocrine, and neurophysiological systems 
have been implicated in the pathogenesis of anxiety states. Much of 
this information has come from animal models and research on the 
effects of stress. Studies of neurobiological functioning in humans 
with GAD are limited. Some of the physical systems that may be 
involved in the emotion of anxiety are summarized below. 
Additional information may be found in reviews by Davidson,(23)
and Gray and McNaughton.(24)
The noradrenergic nervous system. Noradrenergic pathway (the 
locus coeruleus -noradrenaline-sympathetic nervous system )
have long been associated with fear and arousal and play an impor-
tant role in the body’s response to threat. However, their role in 
persistent anxiety states is not clear. Resting catecholamine levels in 
patients with GAD appear to be normal. On the other hand, GAD

patients with GAD appear to be normal. On the other hand, GAD 
patients exhibit subnormal responses to both stimulation(25) and 
blockade(26) of α2-adrenergic receptors and a reduced density of 
α2-receptors in platelets.(27) Those ﬁ  ndings could reﬂ  ect downreg-
ulation of the α2-receptors due to initially high levels of noradren-
aline (norepinephrine).
Consistent with those neurochemical ﬁ  ndings, somatic measures 
of autonomic nervous system function (e.g. skin conductance, 
respiratory rate, heart-rate variability, blood pressure) in patients 
with GAD tend to show normal resting values with blunted 
and sometimes prolonged responses to stressful stimuli.(27)
Psychophysiological studies have found that worry is associated 
with restricted sympathetic arousal and low vagal tone.(27) In con-
trast, it has been shown that compared to controls, individuals with

trast, it has been shown that compared to controls, individuals with 
GAD show greater muscle tension at baseline in response to 
psychological challenge.(28) In addition, structural analyses suggest 
that GAD, unlike other anxiety disorders, is not associated with 
autonomic hyperarousal when levels of negative affect are held constant.(14) These findings indicate diminished autonomic 
nervous system responsiveness in individuals with GAD.
The hypothalamic-pituitary-adrenal axis. The hypothalamic-
pituitary-adrenal axis  and its end-product, cortisol, are also involved 
in reactions to stress. Activity in the hypothalamic-pituitary-
adrenal axis is subject to a variety of inﬂ  uences. Primary control is 
by means of hypothalamic secretion of corticotrophin-releasing 
factor, which stimulates pituitary secretion of ACTH, which in turn 
stimulates adrenal secretion of cortisol. Circulating cortisol, and

stimulates adrenal secretion of cortisol. Circulating cortisol, and 
analogues such as dexamethasone, exert inhibitory feedback at the 
level of the pituitary gland and apparently also by means of recep-
tors on the hippocampus.
In rats, chronic exposure to stress or exogenous steroids results 
in a reduction of corticosteroid receptors in the hippocampus and 
a consequent decrease in feedback inhibition by cortisol.(29) These 
animals exhibit reduced dexamethasone suppression of cortisol 
secretion and greater or more prolonged adrenocortical responses 
to stress. Reduced dexamethasone suppression also has been 
observed in approximately one-third of patients with DSM-III-
diagnosed GAD.(30) This reduction in the normal regulatory 
control of cortisol secretion may be one mechanism through which 
chronic or repeated stress can lead to persistent anxiety.
The amygdala and the bed nucleus of the stria

The amygdala and the bed nucleus of the stria 
terminalis. LeDoux(31) and others have demonstrated the central 
role played by the amygdala  in the mediation of fear reactions. The 
amygdala is thought to be responsible for the detection of potential 
threats to the organism and the mobilization of a range of defen-
sive responses (Fig. 4.7.1.1). Through connections with the 
hypothalamus, it can activate the sympathetic nervous system and 
hypothalamic-pituitary-adrenal axis. Through efferent ﬁ  bres to the 
central grey area of the midbrain, it can mediate behavioural 
defence responses such as the ﬁ  ght-or-ﬂ  ight response and behav-
ioural ‘freezing’ . Through connections to the nucleus reticularis 
pontis caudalis, it can enhance the defensive startle reﬂ  ex.
A structural magnetic resonance imaging (MRI) study of

A structural magnetic resonance imaging (MRI) study of 
children and adolescents found that those individuals with GAD 
had increased total and right amygdala volume compared to non-
anxious controls.(32) In addition, abnormalities in fear circuitry, 
especially hyperactivation in the right amygdala, have been found 
in adolescents with GAD.(33)
The extent to which these pathways are involved in the neurobiol-
ogy of anxiety (as opposed to fear) is unclear. However, a structure 
Fig 4.7.1.1 Fear pathways (based on descriptions by LeDoux(31) and Davis(34)). 
ANS, autonomic nervous system; HPA, hypothalamic-pituitary-adrenal axis.

733
closely related to the amygdala, the bed nucleus of the stria terminalis, 
may be involved in this emotion. The bed nucleus resembles the 
amygdala in its neurotransmitter content, cell morphology, and hypo-
thalamic and brainstem connections and, like the amygdala, it exerts a 
modulating effect on the startle reﬂ  ex.(34) Studies of this latter effect 
implicate it in the experience of anxiety.
Administration of corticotrophin-releasing factor into the 
cerebral ventricles of rats produces a state of generalized arousal 
resembling anxiety. Under those conditions, the startle reﬂ  ex also 
is enhanced. Exposing rats to bright light for 5 to 20 min has 
similar effects. These effects are not blocked by damage to amyg-
dala but are by lesions to the bed nucleus of the stria terminalis 
and by treatment with benzodiazepines or buspirone. Conversely, 
infusion of corticotrophin-releasing factor directly into the bed 
nucleus of the stria terminalis, but not the amygdala, produces a

nucleus of the stria terminalis, but not the amygdala, produces a 
rapid increase in startle. Based on these observations, Davis(34)
has suggested that the stria terminalis may play a role in anxiety 
analogous to that of the amygdala in fear reactions and, further, 
that prolonged or repeated stimulation of the stria terminalis by 
corticotrophin-releasing factor during periods of stress might lead 
to sustained activation and thus to persistent anxiety. A recent 
study has conﬁ  rmed the differential association of these structures 
with fear and anxiety, respectively.(35)
The septohippocampal system (behavioural inhibition 
system). The bed nucleus of the stria terminalis is part of the 
larger septohippocampal system.(36) In 1982, based on data from 
several lines of research, Gray hypothesized that the septohippo-

campal system, together with the Papez circuit (a neural loop 
connecting the subicular area in the hippocampal formation to the 
mammillary bodies, anterior thalamus, cingulate cortex, and back 
to the subiculum), is responsible for mediating the emotion of 
anxiety as well as the major effects of anxiolytic drugs.(36) Gray 
called this network the behavioural inhibition system , because he 
believed that, when activated, it interrupts ongoing behaviour and 
redirects the organism’s attention to signs of possible danger.
According to Gray’s model,(24,36) the behavioural inhibition 
system receives information about the environment from the sensory 
cortex via the temporal lobe and hippocampal formation. The sys-
tem checks the information for consistency with predictions, which

tem checks the information for consistency with predictions, which 
are updated continuously by the Papez circuit based on preceding 
information and stored patterns, as well as for consistency with the 
immediate goals of the organism. When a mismatch is found, or if a 
predicted event is aversive, the outputs of the behavioural inhibition 
system are activated, resulting in a constellation of emotional and 
behavioural effects consistent with anxiety (Fig. 4. 7.1.2).
The activation of the behavioural inhibition system appears to 
be moderated by ascending noradrenergic and serotonergic projec-
tions to the septohippocampal complex, providing a possible 
mechanism for the anxiolytic actions of some drugs. The amygdala 
also provides inputs to the behavioural inhibition system and may 
relay its outputs to the hypothalamus and autonomic nervous 
system, thereby mediating anxious arousal. Sustained activation of

system, thereby mediating anxious arousal. Sustained activation of 
the behavioural inhibition system might therefore account for 
many of the features of GAD.
The benzodiazepine- γ-aminobutyric acid system. The powerful 
anxiolytic and sedative effects of benzodiazepines are believed to be 
mediated by benzodiazepine recognition sites located on 
γ-aminobutyric acid ( GABA ) type A receptor complexes in the 
central nervous system. When bound to those complexes,benzodiazepines allosterically modulate the GABA receptors to 
enhance the normal inhibitory effects of GABA on neurotransmis-
sion. Activation of central benzodiazepine-GABA receptor com-
plexes  also suppresses hypothalamic-pituitary-adrenal axis activity 
and, consequently, cortisol levels.
In addition to these central receptor complexes, benzodiazepine

In addition to these central receptor complexes, benzodiazepine 
recognition sites of a different type are present widely in cells out-
side the central nervous system. These so-called peripheral benzo-
diazepine receptors  are believed to be instrumental in controlling 
the synthesis of regulatory steroids. Their role in the anxiolytic 
actions of benzodiazepines is unknown; although they bind some 
drugs (e.g. diazepam), they have low afﬁ  nity for others (e.g. clonaz-
epam). Interestingly, peripheral benzodiazepine receptors are 
decreased in blood cells of individuals with untreated GAD but 
return to normal levels after successful treatment with benzodiaz-
epines. Their numbers also vary in response to stress, being elevated 
following acute stressors and reduced during chronic stress.
A possible explanation for those changes has been suggested by

A possible explanation for those changes has been suggested by 
Rocca et al.(37) The investigators note that peripheral benzodiaze-
pine receptors in brain glial cells control the production of neuros-
teroids that act as modulators of GABAA receptor sensitivity. Their 
effect on GABA functioning appears to be opposite to that of clini-
cally effective benzodiazepines, that is, they ‘decrease’ rather than 
increase the inhibitory effects of GABA. It is hypothesized that an 
endogenous ligand of these glial cell receptors (possibly diazepam-
binding inhibitor) is released during stress, initiating the cycle of 
events depicted in Fig. 4.7.1.3.
The immediate effect of these events would be to enhance the 
stress-induced release of cortisol. However, prolonged cortisol 
excess is hypothesized to downregulate peripheral benzodiazepine

excess is hypothesized to downregulate peripheral benzodiazepine 
receptors, resulting in the reduced receptor densities found in GAD. 
Administration of a clinically effective benzodiazepine drug would 
interrupt the proposed pathway at the point of the central GABA 
receptor, lowering cortisol levels and restoring synthesis of peripheral 
benzodiazepine receptors.
Other neurotransmitter systems. Individuals with GAD have 
been reported to have reduced serotonin levels in the cerebral 
spinal ﬂ  uid(35) and decreased platelet binding of paroxetine, a selec-
tive serotonin reuptake inhibitor.(38) In addition, drugs that affect 
Fig 4.7.1.2 Behavioural inhibition system (based on descriptions by Gray 
and McNaughton(24)). ANS, autonomic nervous system; 5-HT, serotonin; NA, 
noradrenaline.4.7.1 generalized anxiety disorders

SECTION 4  clinical syndromes of adult psychiatry 734
serotonergic transmission (e.g. buspirone and venlafaxine) are 
effective in the treatment of GAD. These ﬁ  ndings suggest that sero-
tonin regulation may be abnormal in GAD.
Cholecystokinin neuropeptides (CCK-4 and CCK-8S) have been 
implicated in the genesis of arousal and fear responses.(40) It is 
unclear how those effects are mediated; however, cholecystokinin 
interacts with several neurotransmitters and systems believed to be 
involved in anxiety responses, including the noradrenergic nervous 
system, the hypothalamic-pituitary-adrenal axis, the benzodiaze pine-
GABA system, and serotonin.
(ii) Generalized psychological vulnerability
A diminished sense of control. Early experiences of uncontrol-
lability may serve as a psychological vulnerability for emotional 
disorders.(16) Individuals in clinical populations, including people 
diagnosed with anxiety disorders, sexual dysfunctions, and depres-

sion, often perceive themselves as having little control over their 
experiences.(41,42)  Patients with GAD are more likely than controls 
to perceive a lack of control over threatening events and to regard 
ambiguous information as threatening.(43) This perceived lack of 
control may result from a variety of events, including trauma and 
insecure attachment to primary caregivers.(44) In patients with 
GAD, worry may be an ineffective attempt to assert control on 
uncertain future events. Intolerance of uncertainty, a construct 
related to perceived lack of control, has emerged as an important 
variable in the study of anxiety disorders.(45) Deﬁ ned as the inabil-
ity to accept that future negative events may occur, intolerance of 
uncertainty has been associated with symptoms of several anxiety

uncertainty has been associated with symptoms of several anxiety 
disorders, but is greater in individuals with GAD than in patients 
from a mixed anxiety disorder sample.(41)
Parenting. There is an extensive literature on the inﬂ  uences of 
early environmental factors on the development of anxiety and 
other negative emotions in children (for an integrative review, see 
Chorpita and Barlow(46)). Attachment theory holds that parents or 
other consistent caregivers serve an important function in a child’s 
development by providing a protective and secure base from which 
the child can operate. Disruption of this base is hypothesized to lead initially to anxious apprehension and dependency and, if the 
disruption is severe, subsequently to withdrawal and depression.
An important aspect of a healthy parent–child relationship is its 
ability to foster in the child a sense of control over events. According

ability to foster in the child a sense of control over events. According 
to Chorpita and Barlow,(46) an individual who lacks sufﬁ  cient early 
experiences of control may dev elop a general perception of personal 
inefﬁ  cacy, which may predispose him or her to chronic negative 
emotional states such as GAD. Two aspects of parenting appear to 
be important in providing a child with opportunities to experience 
control: responsiveness to the child’s efforts at engagement 
and encouragement of the child to explore and manipulate the 
environment. A parenting style characterized by excessive control 
of the child’s environment (overprotection) coupled with a lack 
of warmth and responsiveness toward the child would deprive the 
child of such opportunities and thus, theoretically, could contribute 
to the development of anxiety.
Consistent with this theory, mothers of anxious preschool children

Consistent with this theory, mothers of anxious preschool children 
were found to be more critical and intrusive and less responsive 
to their children than mothers of non-anxious children.(47)
In addition, adults who rated their parenting as more protective 
and less caring had higher trait anxiety scores than other individu-
als surveyed. A similar pattern was found to distinguish patients 
meeting DSM-III-R criteria for GAD or panic disorder from 
controls.(48) One hypothesis is that the relationship of these early 
parenting experiences to the subsequent development of anxiety 
(or depression) is mediated by the early formation of cognitive vul-
nerability best described as a sense of uncontrollability regarding 
future events in one’s life (Fig. 4.7.1.4).(46)
Specific psychological vulnerability. Data from twin studies

Specific psychological vulnerability. Data from twin studies 
suggest that environmental inﬂ  uences contribute more to the vari-
ance in aetiology of GAD than heredity.(19) In addition, the triple 
vulnerability model of the aetiology of anxiety disorders suggests 
that psychological and biological vulnerabilities interact with Fig 4.7.1.3 Possible involvement of peripheral benzodiazepine receptors in 
acute and chronic stress reactions (based on descriptions by Rocca et al.(37)). 
BZ, benzodiazepine.
Fig 4.7.1.4 Model of the development of vulnerability for anxiety and depression. 
BIS, behavioural inhibition system(24); HPA, hypothalamic-pituitary-adrenal axis 
(Copyright © 1998 by the American Psychological Association. Reproduced with 
permission. Chorpita, B.F. and Barlow, D.H. The Development of anxeity: the role of

permission. Chorpita, B.F. and Barlow, D.H. The Development of anxeity: the role of 
control in the early environment, Psychological Bulletin , 124, 3–2. The use of APA 
information does not imply endorsement by APA).

735
environmental factors (i.e. stressful life events), to produce anxiety 
symptoms that reach a clinical level.(16,17) Several environmental 
factors have been implicated.
Stressful life events. Several studies have found an association 
between stressful or traumatic life events and GAD. The natures of the stressors that precede the onset of GAD remain unclear. However, in one study, 52 per cent of individuals diagnosed with GAD reported experiencing at least one past traumatic event (i.e. an event that would meet for Criterion A of the DSM-IV deﬁ  nition 
of PTSD), compared to only 21 per cent of non-anxious controls. It was unclear in this study if the events occurred prior to the onset of the GAD.
(49) In addition, a variety of stressors have been associated 
with increased risk of GAD, including early parental death,(50) rape 
or combat,(51) and chronically dysfunctional marital and family 
relationships.(52)
Course and prognosis. Although there is evidence to the

Course and prognosis. Although there is evidence to the 
contrary, GAD has often been considered a chronic and disabling condition. The Harvard/Brown Anxiety Research Program study provides information on the course and impact of GAD among patients treated naturalistically over a 3-year period.
(53) The mean 
age at onset of GAD was 21 years (range 2–61 years), and theaverage duration of illness at initial evaluation was 20 years. Excluding patients with comorbid panic disorder, one-thirdof subjects had never married and another 17 per cent wereseparated, widowed, or divorced. Unemployment was higherthan average, and 37 per cent of subjects had received public ﬁ nancial assistance. Despite the fact that more than 80 per cent of

patients received treatment during the study period, remission from GAD was uncommon (15 per cent at 1 year, 27 per cent by3 years). Among patients with comorbid psychiatric disorders,the proportions achieving remission from GAD and coexisting 
anxiety disorders were only 8 per cent and 17 per cent at 1 and3 years, respectively.
However, there is evidence that the perception of GAD as 
a chronic, unremitting condition may not be completely correct. A longitudinal study of individuals with GAD found that many (46 per cent of women and 56 per cent of men) experienced episodes of full remission and that the periods with no symptoms last longer in women.
(54)
Treatment
(a) Pharmacotherapy
Several pharmacological agents have been shown to be effective for the treatment of GAD (for a review, see Davidson
(23)). Chief among

(54)
Treatment
(23)). Chief among 
these are the benzodiazepines, azapirones, and antidepressants. Evidence shows that several types of medications may be effective for at least short-term relief of anxiety, however, many are not effective in the long term unless taken indeﬁ  nitely.
(55)
(i) Benzodiazepines
Benzodiazepines have for decades been prescribed for short-term 
relief of anxiety.(55) Although, evidence demonstrates that these 
drugs can be effective in relieving anxiety for a short period, there is little or no evidence that they work over a long period. However, compared with other agents used to treat anxiety disorders, they are safe, fast-acting, and have relatively few side-effects. All currently available benzodiazepines probably are efﬁ  cacious for

GAD. Approximately two-thirds of patients experience moderate to marked improvement, with effects being evident within the ﬁ  rst 
1 or 2 weeks of treatment.
(56)
Benzodiazepines appear to be more effective for the somatic 
symptoms of GAD than for psychic symptoms such as apprehen-sive worry and irritability, possibly because of their sedative and myorelaxant properties. In some studies, irritability actually has increased during treatment with benzodiazepines. Consequently, these drugs may be better for patients whose complaints are more somatic than psychic, whereas other agents may be better when the reverse is true.
(ii) Azapirones

In recent years, azapirone drugs have become a popular alternative to benzodiazepines for the treatment of GAD. These drugs lack the sedative and muscle relaxant properties of the benzodiazepines as well as their ability to potentiate the effects of alcohol. However, improvement is somewhat slower (2–4 weeks) than with benzodi-azepines. The most widely used of these agents is buspirone, whose efficacy and safety have been demonstrated in several well-controlled trials (see Rickels
(57) for a review) and became, in 1996, 
the only non-benzodiazepine approved by the U.S. Food and Drug Administration for the treatment of GAD.
(58) It is as effective as 
benzodiazepines for general anxiety and may reduce some of the associated features of GAD as well, including depression and agita-tion. Buspirone also does not seem to be associated with as much dependence and withdrawal as found with the benzodiazepines.
(55)

(55)
Ipsapirone, an azapirone with somewhat greater affinity and selectivity for the 5-hydroxytryptamine-1A receptor and fewer side-effects than buspirone also appears to be effective.
(59) Other 
drugs in this class include gepirone, tandospirone, and ﬂ  esinoxan.
(iii) Antidepressants
Both imipramine and trazodone have been superior to placebo for 
the treatment of GAD in controlled trials. In one trial, the two drugs were comparable to each other and to diazepam in reducing anxiety after the ﬁ  rst 2 weeks of treatment.
(56) In another study, 
imipramine was as effective as chlordiazepoxide overall and pro-duced greater reductions in associated depression. In addition, nefazodone, an agent related to trazodone but less sedating, was effective for GAD in a small open trial.
(60)
Many studies have examined the use of newer antidepressants,

(60)
Many studies have examined the use of newer antidepressants, 
including selective reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SRNIs), in the treatment of GAD and have had favourable results. One placebo-controlled study of the SSRI paroxetine found that 62 per cent and 68 per cent of patients receiving 20 and 40 mg of paroxetine had signiﬁ  cant 
reduction in symptoms, compared to only 46 per cent in the placebo group.
(61) In addition, due to results from several large, 
placebo-controlled trials, venlafaxine was the ﬁ  rst antidepressant 
approved by the Federal Drug Administration for the treatment of GAD.
(62,63)
(b) Psychosocial treatment
Early psychological treatments for GAD consisted mostly of non-speciﬁ  c interventions such as supportive psychotherapy, relaxation

(62,63)
Early psychological treatments for GAD consisted mostly of non-speciﬁ  c interventions such as supportive psychotherapy, relaxation 
training, and biofeedback. In general, those treatments were not very effective. However, cognitive behavioural treatment (CBT) has been found in several randomized controlled trials to be associated with clinically signiﬁ  cant improvement. Cognitive behavioural 
treatment consists of psychoeducation about the nature of anxiety, 4.7.1 generalized anxiety disorders

SECTION 4  clinical syndromes of adult psychiatry 736
symptom monitoring, relaxation training, exposure (imaginal and 
in vivo ), and cognitive restructuring. Psychoeducation is a com-
mon CBT component in which the nature of anxiety is discussed in order to normalize the patient’s experience. It also serves to teach patients to differentiate between adaptive and maladaptive anxiety. Symptom monitoring allows records of mood and anxiety to be recorded and allows patients to learn to observe their symptoms. Progressive muscle relaxation (PMR) is a common technique used to teach patients relaxation strategies to use in anxiety-provoking situations. Exposures are tailored to the nature of GAD and are either in vivo  or imaginal and are often combined with rehearsal of

coping skills (i.e. PMR) until anxiety subsides. Cognitive restruc-turing targets distorted cognitions and information-processing biases associated with GAD. Strategies to challenge catastrophizing or overestimating the probability of a negative event are often employed during this component of treatment. CBT is typically administered in a dozen or so sessions, and can be conducted in group or individual formats. In controlled trials, cognitive behavioural treatments have been more effective than no treatment or a psychological or drug placebo treatment and at least as effec-tive as benzodiazepines (for a review, see Barlow et al. ).
(64) Attrition 
is low (10–15 per cent), and reductions in anxiety average about 50 per cent, with gains being maintained at follow-up. Currently, the most successful treatments combine relaxation training with cognitive interventions focused on making the worry process more controllable.
Consistent with the ﬁ  ndings of individual studies, meta-analyses

Consistent with the ﬁ  ndings of individual studies, meta-analyses 
for GAD have found that CBT is more efﬁ  cacious than control con-
ditions, resulting in medium to large effect sizes when compared to pill or psychological placebo.
(65) However, in studies directly com-
paring CBT with pharmacotherapy (most often benzodiazepines), there was no difference in effect sizes between the two treatments. Currently, neither mode of treatment has been shown to be consis-tently superior to the other.
Recent developments in psychosocial treatments for GAD have 
integrated acceptance and mindfulness approaches into traditional CBT.
(66) These treatments are based on the notion that individuals’ 
attempts to control their internal experience often backﬁ  re, result-
ing in increased anxiety. Components to these treatments may include experiential exercises, mindfulness training, identiﬁ  cation

ing in increased anxiety. Components to these treatments may include experiential exercises, mindfulness training, identiﬁ  cation 
of overriding values, and encouragement towards taking action in ways that are consistent with these values.
(66)Further exploration 
with controlled trials needs to be conducted to examine the efﬁ  cacy 
of these newer approaches with cognitive behavioural treatments.
(c) Combined pharmacotherapy and psychotherapy
Although common in clinical practice, little is known about the effects of combining pharmacotherapy and psychotherapy for GAD. In the only published study to date, Power et al.
(67) compared

(67) compared 
cognitive behavioural therapy, diazepam, a pill placebo, cognitive behavioural therapy plus diazepam, and cognitive behavioural therapy plus a pill placebo in a sample of DSM-III-diagnosed GAD patients. At post-treatment and follow-up, patients in all three cognitive behavioural therapy conditions were more improved than those who received diazepam or placebo alone. Although the cognitive behavioural therapy groups did not differ signiﬁ  cantly 
from each other on any measure, the cognitive behavioural therapy plus diazepam group improved earliest and had the largest percent-age of patients achieving a criterion of clinically signiﬁ  cant change on all measures. Unfortunately, the use of DSM-III criteria in this

study makes its relevance to GAD as it is currently defined uncertain. In addition, the cognitive behavioural therapy used was briefer (seven sessions) and less speciﬁ  c than the currently 
recommended forms.
(d) Effect of comorbidity on treatment outcome and vice versa
Many treatment trials investigating GAD have excluded patients with comorbid Axis I disorders. A review of 48 GAD studies pub-lished between 1980 and 1991 found that only eight reported including patients with other psychiatric disorders.
(68) When

(68) When 
comorbid disorders have been permitted, their effect on treatment outcome generally has not been evaluated. In the Harvard-Brown Anxiety Research Program study, the presence of a comorbid psy-chiatric disorder reduced response rates at 1 and 3 years by nearly 50 per cent. In addition, it has been found that concurrent person-ality disorders impair outcome of treatment for GAD. In one study improvement was comparable among treatment completers with or without Axis II disorders, but attrition was greater in the former (44 per cent) than the latter (19 per cent) group.
(69)
The high rates of comorbidity associated with GAD have impor-
tant implications for treatment. Higher rates of comorbidity are associated with lower rates of remission and greater likelihood of relapse over 12-year follow-up.
(70) On the other hand, successful 
treatment of GAD in patients with comorbid disorders often reduces the severity of the other disorders as well. Borkovec et al.
(68)

(68)
examined the effect of various psychosocial treatments for GAD on 
coexisting anxiety and mood disorders (except panic disorder or severe depression, which were excluded from the study). Across treatments, patients whose GAD improved exhibited reductions as well in other anxiety disorders (mostly social and simple phobia) and dysthymia. Only 4 of 13 successfully treated patients who had additional disorders at pre-treatment continued to have them at post-treatment.
Many anxious patients do not meet diagnostic criteria for GAD. These patients often respond to conservative measures. If the symptoms are minor or are related to a situational stressor, brief psychotherapy and support is the treatment of ﬁ  rst choice. In one

study, patients who initially reported physical or minor emotional complaints responded better to counselling than to diazepam, even when counselling was limited to only 3 h.
(72) Often, an explanation 
of the relationship of physical symptoms to stress is reassuring to patients and can interrupt a spiral of symptoms leading to anxiety and worry about health, leading to increased symptoms, and so on. Simple behavioural interventions such as relaxation training for patients with prominent muscle tension or breathing exercises for those with dyspnoea or hyperventilation may be helpful as well.
For patients with marked adrenergic symptoms or insomnia, the 
temporary (a few days to a few weeks) use of a benzodiazepine may be helpful as an adjunct to psychotherapy. In some cases, a hypnotic drug alone is sufﬁ  cient. In general, as-needed use of

temporary (a few days to a few weeks) use of a benzodiazepine may be helpful as an adjunct to psychotherapy. In some cases, a hypnotic drug alone is sufﬁ  cient. In general, as-needed use of 
benzodiazepines should be discouraged, because it is more likely than scheduled use to foster reliance on drugs as the principal means of coping with anxiety. For the same reason, the drug dose 
should be kept as low as possible and should be tapered as therapy 
proceeds.

737
For patients meeting diagnostic criteria for GAD, treatment with 
an empirically validated form of psychosocial therapy for GAD is strongly recommended. Such treatments are available in manual-ized form with accompanying patient workbooks.
(55)
When medication treatment is preferred, a trial of buspirone is a 
good initial choice. Exceptions are patients with comorbid panic disorder or marked adrenergic symptoms, for which benzodiaze-pines may be better if they are not contraindicated (see below). The typical starting dose of buspirone is 15 mg/day in divided doses (5 mg thrice daily or 7.5 mg twice a day), which is increased by 5 mg/day every few days to a target dose of 30 mg/day. If the response is insufﬁ  cient after 2 to 4 weeks at that amount, or if 
the patient is experiencing signiﬁ  cant depressive symptoms, the 
dose may be advanced gradually to a maximum of 60 mg/day. Improvement may continue for up to 3 months.

It is important to inform patients of the typical side-effects and 
response time of buspirone. Patients who have taken benzodiaze-pines previously may expect prompt relief and sedative side-effects 
from the medication and may become discouraged when these are absent. When switching from a benzodiazepine to buspirone, 
it may be helpful to continue the benzodiazepine during the ﬁ  rst 
month of buspirone therapy before initiating a gradual taper. Remember that buspirone will not prevent benzodiazepine with-drawal symptoms.
Failing a course of buspirone, or in patients with comorbid major

Failing a course of buspirone, or in patients with comorbid major 
depression, trials of antidepressant medications (e.g. imipramine, venlafaxine, trazodone) would be a reasonable second choice. Venlafaxine may be effective at doses as low as 75 mg/day (the usual starting dose). Because of its short metabolic half-life, the extended release form is preferred, which allows once per day dosing and thus may improve compliance. The dose typically is advanced by 75 mg/day every 2 weeks to a maximum of 225 mg/day. Dosing for other antidepressants is the same as for the treatment of depression.
Because of the risk of dependence and (uncommonly) abuse, 
long-term use of benzodiazepines generally is reserved for patients who do not respond sufﬁ  ciently to other options. Relative contra-

indications include a need to be alert (e.g. drivers and machinery operators), a personal or family history of alcoholism or drug abuse, and prominent aggressiveness or irritability. Generally, lon-ger half-life benzodiazepines (e.g. diazepam, clonazepam), which can be taken once or twice daily, are preferred. A typical starting dose is 5 to 10 mg/day of diazepam or equivalent, which is advanced every few days to a maximum of 40 mg/day.
In instances where pharmacotherapy is the primary treatment, 
responders should be continued on medication for at least 6 months 
before a gradual drug taper is attempted. Even so, a substantial

before a gradual drug taper is attempted. Even so, a substantial 
proportion will relapse after drug discontinuance and will require further treatment. Discontinuing pharmacotherapy in the context of effective psychosocial treatment may improve success rates.
Based on current knowledge, GAD seems to be the exaggerated expression of the human potential to apprehensively anticipate and prepare for future misfortune. As such, it may represent a ‘basic’ disorder, a better understanding of which may shed light on other anxiety and mood disorders. Although the deﬁ  nition of 
GAD has been revised considerably since being given status of a full disorder in DSM-III-R, much more information needs to be

GAD has been revised considerably since being given status of a full disorder in DSM-III-R, much more information needs to be 
gathered regarding psychosocial treatments for GAD. In addition, due to its poor diagnostic reliability, many revisions to the diagnostic criteria of GAD have been suggested. Despite the progress in eluci-dating the nature of GAD, further research needs to be conducted to continue to enhance our understanding and development of effective and generalizable treatments.
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4.7.2 Social anxiety disorder 
and speciﬁ  c phobias
As our classiﬁ  cation systems have been reﬁ  ned, we have come to 
view social anxiety disorder (social phobia) and speciﬁ  c phobias as 
distinct disorders, with divergent patterns of prevalence, aetiology, and course. Moreover, treatments for these disorders have become 
increasingly sophisticated. This chapter presents an overview of the current state of the ﬁ  eld with regard to social anxiety disorder and 
speciﬁ  c phobias.
Social anxiety disorder
In the ﬁ  rst and second editions of the Diagnostic and Statistical 
Manual of Mental Disorders (DSM ),(1,2) all phobias were grouped

Manual of Mental Disorders (DSM ),(1,2) all phobias were grouped 
together. However, in 1966 Marks and Gelder(3) observed that 
various phobias had different ages of onset and symptom presenta-tions, providing the initial impetus for the inclusion of social 
phobia  as a distinct disorder in DSM-III.
(4) At ﬁ  rst, research into 
the nature and treatment of social phobia lagged behind that of other anxiety disorders, leading to its description in 1985 as the neglected anxiety disorder.
(5) Over the past two decades, however, 
attention to the conceptualization, deﬁ  nition, and classiﬁ  cation 
of social phobia has increased dramatically. T o acknowledge the signiﬁ  cant impairment now known to be associated with social 
phobia and its differentiation from speciﬁ  c phobia, the alternative 
(and increasingly utilized) label, social anxiety disorder , was added 
in DSM-IV .

in DSM-IV .
(6)4.7.2 social anxiety disorder and specific phobias

SECTION 4  clinical syndromes of adult psychiatry 740
Clinical presentation
Anxiety in situations involving potential evaluation by others 
(e.g. job interviews, public speaking engagements, ﬁ  rst dates) falls 
within the realm of ‘normal’ social anxiety. For individuals with social anxiety disorder, however, situations such as these are typi-cally associated with incapacitating levels of anxiety and a desire for escape or avoidance. Socially anxious individuals are often self-critical and perfectionistic and go to great lengths to avoid the negative evaluation of others that they may perceive as epidemic. 
Commonly, persons with social anxiety disorder experience

Commonly, persons with social anxiety disorder experience 
somatic symptoms such as blushing, trembling, dry mouth, or perspiring, which they believe will be noticed by others and provide further evidence of their incompetence. Children may manifest their anxiety differently than adults; they may cry, throw tantrums, freeze, shrink from interactions with strangers, and they may not acknowledge that their fears are irrational.
(6) By leaving 
anxiety-provoking situations (escape) or foregoing them entirely (avoidance), individuals with social anxiety disorder may reduce or prevent the immediate experience of anxiety, but this behaviour reinforces beliefs in their inadequacies and serves to maintain anxi-ety in the absence of objective threat.
(7,8)
Individuals with social anxiety disorder experience signiﬁ  cant 
impairment in social, educational, and occupational function-ing.
(5,9) They are less likely to marry and are more likely to divorce

(5,9) They are less likely to marry and are more likely to divorce 
than those without the disorder.(10) They also have fewer friends 
and more trouble getting along with the friends they have than persons without the disorder.
(11) Individuals with social anxiety 
disorder assessed in a primary care setting reported missing an average of 3 days of work and having an average of 6 days of reduced productivity in the last month because of their emotional problems.
(12) Comparatively, mentally healthy individuals
reported less than 1 day of lost work and reduced productivity combined. Unemployment, underemployment (working at alevel below the individual’s abilities), and ﬁ  nancial dependency 
are also characteristic of individuals with social anxietydisorder.
(10)
(a) DSM and ICD

(10)
Whereas the DSM is widely used in North America, the International 
Classification of Mental and Behavioural Disorders (ICD ) is 
commonly used in other parts of the world. Social anxiety disorder, termed social phobia in ICD-10,
(13) ﬁ rst appeared in ICD-10 
12 years after its appearance in DSM-III. The ICD-10 criteria for social phobia are less detailed and more circumscribed than those in DSM-IV . Speciﬁ  cally, DSM-IV requires excessive fear of humili-
ation or embarrassment in social or performance situations, anxiety provoked by exposure to feared situations, recognition that the fear is excessive, avoidance of situations or endurance with dis-tress, and signiﬁ  cant distress or impairment. Further, the fear and

avoidance cannot be better accounted for by another psychiatric disorder, a general medical condition, or the effects of a substance. The ICD-10, in contrast, requires only that the symptoms be repre-sentative of anxiety and not another psychiatric disorder, that the anxiety occurs in relation to social situations, and that avoidance of anxiety-provoking situations be present. Because most published research on social anxiety disorder relies on DSM rather than ICD 
criteria, this chapter will do so also.
(b) Diagnostic issues
Individuals presenting for treatment of social anxiety disorder 
endorse multiple fears and signiﬁ  cant impairment. The generalized
subtype is speciﬁ  ed when ‘most social situations’ are feared, where-
as the non-generalized subtype describes persons who fear a more

as the non-generalized subtype describes persons who fear a more 
limited set of social situations. Individuals with generalized and non-generalized social anxiety disorder differ on several dimen-sions, including symptom severity, functional impairment, and physiological symptoms when exposed to feared situations.
(14)
Conclusive differences between subtypes in course and response to treatment remain to be demonstrated.
(15,16)
Like social anxiety disorder, avoidant personality disorder is 
regarded as an extreme fear of negative evaluation, leading research-ers to view the two conditions on a continuum that is artiﬁ  cially 
divided at the boundary between Axes I and II. Many investigators conclude that the co-occurrence of generalized social anxiety disorder and avoidant personality disorder represent persons with the most severe social anxiety and the poorest global functioning.
(17)

(17)
Social anxiety may also develop as a result of medical conditions, 
such as becoming excessively anxious or avoiding social situations because of obesity, acne, benign essential tremor, stuttering, or the disability associated with Parkinson’s disease. These conditions are not considered exemplars of social anxiety disorder because anxi-ety developed secondary to the medical condition. Rather, they are assigned to the category ‘anxiety disorder not otherwise speciﬁ  ed’ . 
However, persons who experience secondary social anxiety are often responsive to pharmacological or cognitive behavioural treatments with demonstrated efficacy for social anxiety disorder.
(18)
(c) Comorbidity and differential diagnosis
Approximately 81 per cent of persons with primary social anxiety 
disorder meet criteria for at least one other lifetime psychiatric disorder.
(19) Social anxiety disorder most commonly co-occurs 
with other anxiety disorders,(20) although comorbid diagnoses of

with other anxiety disorders,(20) although comorbid diagnoses of 
depression and alcohol use disorders are also common. Differential diagnosis is complicated by the fact that certain Axis I disorders both resemble and co-occur with social anxiety disorder.
(d)  Social anxiety disorder versus panic disorder with 
agoraphobia (PDA)
PDA can be differentiated from social anxiety disorder in several 
ways. Although many individuals with social anxiety disorder expe-rience panic attacks, the attacks occur in anticipation of negative evaluation by others. For persons with panic disorder, panic attacks are often unexpected, may not be associated with speciﬁ  c cogni-
tions, and can be nocturnal.
(5) Persons with social anxiety disorder

(5) Persons with social anxiety disorder 
are more likely to experience blushing and muscle twitches, whereas individuals with PDA are more likely to experience symp-toms such as blurred vision, headaches, chest pain, ringing in the ears, and fear that they will die or go crazy.
(21) The age of onset for 
social anxiety disorder tends to be earlier than that for PDA.(22)
Individuals presenting for social anxiety disorder treatment either show an equal gender distribution or are slightly more likely to be male,
(23) whereas those presenting for PDA treatment are substan-
tially more likely to be female.(21) Finally, persons with social

741
anxiety disorder report feeling more comfortable when alone, 
whereas persons with PDA may feel more at ease in the presence of others.
(22)
(e)  Social anxiety disorder versus generalized anxiety 
disorder (GAD)
Individuals with GAD endorse higher levels of social anxiety than 
other persons with non-social anxiety disorders.(23) Although indi-
viduals with either social anxiety disorder or GAD may devote excessive amounts of time to worrying and ruminating, the focus of worry in social anxiety disorder is on fear of evaluation in social or performance situations, whereas the hallmark feature of worry in GAD is heightened focus on possible catastrophic consequences across several domains of life. Persons with social anxiety disorder are more likely to experience sweating, ﬂ  ushing, and breathing 
problems; those with GAD more commonly experience headaches, insomnia, and fear of dying.
(24)
(f) Social anxiety disorder versus depression

(24)
Social anxiety disorder and depression may have withdrawal from 
social situations in common.(21) In differentiating between the two 
disorders, one must consider the reason for this withdrawal. Persons with depression withdraw because they fail to experience pleasure or lack the energy for social engagement. Individuals with social anxiety disorder fear the negative evaluation they believe to be associated with such situations. Persons with depression may be indifferent about engaging in social situations, whereas individuals with social anxiety disorder often have a strong desire to afﬁ  liate 
with others that is hampered by anxiety.
The National Comorbidity Survey Replication ( NCS-R ) reported 
a lifetime prevalence rate of 12.1 per cent(25) and a 12-month prev-

alence rate of 6.8 per cent(20) for social anxiety disorder. NCS-R 
lifetime prevalence rates render social anxiety disorder the fourth most common psychiatric disorder behind major depression (16.6 per cent), alcohol abuse (13.2 per cent), and speciﬁ  c phobia 
(12.5 per cent).
(b) Age at onset/age of treatment seeking
Social anxiety disorder often begins early in life. Mean age of onset 
for the disorder ranges from 13 to 20 years old, although patients often report having experienced symptoms for as long as they can remember.
(26) Despite early onset, persons with social anxiety 
disorder often do not seek treatment for approximately 16 years after onset,
(27) and many never do.(28)
(c) Gender differences
Although men and women with social anxiety disorder who seek

Although men and women with social anxiety disorder who seek 
treatment do so in relatively equal numbers,(23) epidemiological 
studies suggest that women are more likely than men to have the disorder.
(19,25)  In a clinical sample, women reported fear of more 
social situations and scored higher on several social anxietydisorder assessment measures.
(29) Thus, although women are more 
likely to experience social anxiety, men are more likely to seek treatment and may do so when troubled with less severesymptoms. It may be that social anxiety disorder impairs the expected role functioning of men to a greater extent that it does for women.
(29)Aetiology of social anxiety disorder

Genetic factors appear to contribute to the emergence of social anxiety disorder. Higher rates of social anxiety disorder have been found in relatives of individuals with the disorder compared to relatives of persons without the disorder.
(30) Further, rates of social 
anxiety disorder in ﬁ  rst-degree relatives of probands with the gen-
eralized subtype are higher than in relatives of probands with the non-generalized subtype or with no psychiatric history.
(31) Kendler 
et al.(32) report concordance rates for social anxiety disorder among 
monozygotic twins (24.4 per cent) to be greater than the rates for dizygotic twins (15.3 per cent). A study conducted with the same cohort 8 years later found the heritability of social anxiety disorder to be approximately 50 per cent in female twins
(33) and 25 per cent 
in male twins.(34)
Neurobiological factors may also be associated with social

Neurobiological factors may also be associated with social 
anxiety disorder. Imaging studies of individuals with social anxiety disorder have demonstrated increased activity in regions associated with fear and anxiety (i.e. prefrontal cortex, amygdala, hippocam-pus) during anxiety-provoking tasks.
(35) Given the efﬁ  cacy of 
serotonin reuptake inhibitors and monoamine oxidase inhibitors in treating social anxiety disorder,
(36) dysregulation of the sero-
tonin(37) and dopamine(38) systems have been investigated as 
potential correlates of the disorder.
Several studies also suggest the importance of parental inﬂ  uences 
and signiﬁ  cant life events in the development of social anxiety dis-
order. Persons with social anxiety recall observing their mothers act more fearful and avoidant of social interactions
(39) and describe 
their parents as overprotective.(40) Stressful social and performance

their parents as overprotective.(40) Stressful social and performance 
situations early in life (e.g. public ridicule, being bullied, mind going blank during a presentation) are also commonly reported by persons with social anxiety disorder.
(41)
Course of social anxiety disorder
Social anxiety disorder is chronic and unlikely to remit without treatment. The disorder persists throughout adulthood
(42) and its 
course is unrelated to gender, age of onset, duration of illness, level of functioning at intake, lifetime history of anxiety disorders, or current comorbidity of anxiety or depressive disorders.
(42,43) Two 
conditions related to social anxiety disorder emerge in childhood and are relatively stable into adulthood—shyness and behavioural inhibition. Individuals who had been shy as children exhibited overall lower levels of functioning when assessed 30 years later.
(44)

(44)
Similarly, children described as behaviourally inhibited, or having the tendency to withdraw from novel people, settings, or objects, have demonstrated increased risk for the development of social anxiety disorder in adolescence.
(45) Behavioural inhibition was also 
more prevalent in children of individuals with anxiety disorders and remained relatively stable for over 7 years in children initially assessed between the ages of 21 to 31 months.
(46) These ﬁ  ndings 
suggest that extreme shyness and behavioural inhibition may be early manifestations of social anxiety disorder.
Empirically evaluated treatments
(a) Cognitive behavioural interventions
Cognitive behavioural treatments have been subjected to the most thorough evaluation in the empirical literature. Treatments that utilize exposure alone or combined with cognitive restructuring have received the greatest empirical support and are the focus of 4.7.2 social anxiety disorder and specific phobias

SECTION 4  clinical syndromes of adult psychiatry 742
our review. Because of space limitations, other cognitive behav ioural 
treatments, such as social skills training and applied relaxation, will not be reviewed, and the reader is referred to other sources.
(47)
(b) Exposure
Exposure requires individuals to imagine (imaginal exposure) or directly confront ( in vivo  exposure) feared stimuli. Research exam-
ining the efﬁ  cacy of imaginal exposure for social anxiety disorder is 
limited; however, in vivo  exposure has repeatedly demonstrated 
short- and long-term efﬁ  cacy in therapist-directed and self-directed 
formats.
(47) Exposure requires patients to progressively confront

formats.
(47) Exposure requires patients to progressively confront 
anxiety-provoking situations beginning with situations that elicit moderate fear. Patients turn to the next most feared situation after repeated and prolonged exposure to the previous situation no longer elicits a distressing level of fear. Individuals with social anxiety disorder treated with exposure alone experienced greater improvement than individuals receiving relaxation training,
(48)
pill placebo,(49) or delayed treatment.(50)
(c) Exposure combined with cognitive restructuring
Contemporary cognitive behavioural models of social anxiety dis-order propose that anxiety is largely maintained by dysfunctional beliefs and information-processing biases, and that successful treatment will be associated with modiﬁ  cation of cognition.
(7,8)
Accordingly, exposure is typically combined with techniques

(7,8)
Accordingly, exposure is typically combined with techniques 
designed to modify dysfunctional thinking patterns.(51,52)
Cognitive restructuring is an intervention based on the theory 
that one’s thoughts about a situation, not the situation itself, generate anxiety.
(53) The intervention is designed to help patients 
challenge maladaptive beliefs by identifying irrational thoughts, evaluating the dysfunction inherent in these thoughts, and deriving rational alternatives to these thoughts. By engaging in this process and utilizing alternative thoughts during exposure to feared situa-tions, patients acquire new, adaptive learning that competes with their previously-learned maladaptive views, and, in turn, lessens the anxiety they experience.
(54)
Efﬁ cacy for the combination of cognitive restructuring and 
exposure has been demonstrated in comparison to wait-list control conditions,
(55,56)  pill placebo,(57) and psychological placebo

(54)
(55,56)  pill placebo,(57) and psychological placebo 
conditions.(57,58) Several studies demonstrate equivalent outcomes 
for exposure alone and exposure plus cognitive restructuring, whereas others indicate the combination shows superior efﬁ  cacy 
and additional gains at follow-up.
(47) In one meta-analysis,(59) only 
the combination of exposure and cognitive restructuring was superior to placebo treatments, but this difference has not been reliably demonstrated.
(60) Nevertheless, patients treated with 
exposure alone tend to show deterioration of gains after treatment, suggesting durability of gains may be enhanced with the addition of cognitive restructuring techniques.
(d) Cognitive behavioural group therapy (CBGT)
CBGT, originally developed by Heimberg and Becker,(51) is one of

CBGT, originally developed by Heimberg and Becker,(51) is one of 
the most thoroughly examined cognitive behavioural treatments for social anxiety disorder. It integrates cognitive techniques and exposure and is typically conducted in 12 weekly, 2.5 h sessions, with approximately six patients and two therapists. In sessions 1–2, patients receive psychoeducation, rationale and instructions for exposure, training in cognitive restructuring, and homework assignments. Thereafter, therapists lead patients through individu-alized exposures preceded and followed by therapist-directed cognitive restructuring exercises. For homework, patients practice 
cognitive restructuring before and after exposure to real-life anxiety-provoking situations.
One study evaluating the efﬁ  cacy of CBGT compared it to

One study evaluating the efﬁ  cacy of CBGT compared it to 
educational-supportive group therapy (ES), a credible placebo treatment consisting of lectures, discussions, and social support. Seventy-ﬁ  ve per cent of CBGT patients made signiﬁ  cant improve-
ment compared to 40 per cent of ES patients.
(58) At follow-up 
(4.5–6.25 years), CBGT produced durable treatment gains.(61)
A comparison of CBGT to the monoamine oxidase inhibitor phen-elzine, pill placebo, and ES demonstrated equivalent response and attrition rates after 12 weeks of treatment for CBGT and phenel-zine, both of which were superior to placebo and ES.
(57) Although

(57) Although 
the phenelzine group evidenced superior improvement on a subset of measures after 12 weeks, CBGT demonstrated more durable treatment gains, with only 17 per cent relapse compared to 50 per cent relapse in the phenelzine group after a 6-month maintenance phase and 6-month follow-up phase.
(62) An intensive version of 
CBGT, based on a hybrid of the treatment approaches developed by Heimberg and by Clark, involving 2 weeks of daily treatment sessions separated by 1 week of homework assignments, also proved superior to a wait-list control.
(63)
(e) Individual cognitive behavioural therapy
Group CBT may not always be feasible, particularly in clinical set-tings where it may be difﬁ  cult to obtain an adequate number of 
patients to form a group. However, CBGT has been adapted to an individual format and proven superior to a wait-list control (Heimberg, unpublished observations). Clark
(52) also developed a

(52) also developed a 
cognitively-focused individual treatment for social anxiety disorder that has demonstrated substantial efﬁ  cacy. The treatment instructs 
patients on how to shift their attention externally (rather than on the self) and to reduce reliance on safety behaviours. Video feed-back and exposure to feared situations aimed at restructuring distorted cognitions are also incorporated.
Individual cognitive therapy demonstrated superior efﬁ  cacy to 
wait-list control, with clinically signiﬁ  cant gains observed in 76 per 
cent of patients receiving cognitive therapy, compared to 38 per cent of patients receiving an applied relaxation treatment and 0 per cent of patients in the wait-list control group.
(64) Cognitive therapy was 
also more efﬁ  cacious than ﬂ  uoxetine plus self-exposure instructions

also more efﬁ  cacious than ﬂ  uoxetine plus self-exposure instructions 
and placebo plus self-exposure instructions, with gains maintained at 1-year follow-up.
(65) Although meta-analytic studies suggest that 
individual and group CBT are similar in efﬁ  cacy,(60) individual cog-
nitive therapy was superior to a group therapy based on Clark’s model on several measures.
(66) Similarly, individual cognitive ther-
apy proved superior to a 3-week intensive group therapy based on Clark’s model and treatment with psychiatrist-selected SSRIs.
(67)
Pharmacotherapy
The efficacy of selective serotonin uptake inhibitors ( SSRI s), 
serotonin–norepinephrine reuptake inhibitor venlafaxine ( SNRI s), 
benzodiazepines, reversible and irreversible monoamine oxidase inhibitors ( MAOI s), ß-adrenergic blockers, buspirone, gabapentin, 
and pregabalin have been evaluated in placebo-controlled studies. T o date, most controlled trials have included patients with general-

ized social anxiety disorder, so it is unclear if similar efﬁ  cacy would 
be observed among patients with the non-generalized subtype of 
the disorder.

743
(a) Selective serotonin reuptake inhibitors and venlafaxine
The SSRIs (e.g. paroxetine, sertraline, ﬂ  uoxetine, ﬂ  uvoxamine, and 
escitalopram) and the SNRI venlafaxine are regarded as ﬁ  rst-line 
medication treatments for generalized social anxiety disorder, given demonstrated efﬁ  cacy in placebo-controlled trials for the disorder 
as well as for other anxiety and affective disorders. Further, poten-tial adverse side effects of SSRIs (e.g. sweating, sexual dysfunction) pose a lower risk than potential adverse side effects of the MAOIs (e.g. high blood pressure, seizure) or benzodiazepines (e.g. depen-dence, overdose).
The SSRIs have demonstrated superior efﬁ  cacy to placebo 
as well as CBT in the short-term,
(68) with the possible exception 
of ﬂ uoxetine.(65,69)  There have been few direct comparisons of

of ﬂ uoxetine.(65,69)  There have been few direct comparisons of 
the various SSRIs or SNRIs. One study comparing escitalopram (5, 10, 20 mg), paroxetine (20 mg), and placebo, demonstrated superior efﬁ  cacy for 5 mg and 20 mg of escitalopram and 20 mg
of paroxetine compared to placebo at week 12.
(70) At week 24, all 
doses of escitalopram proved superior to placebo and 20 mgof escitalopram proved superior to paroxetine on a subset of social anxiety measures. The SNRI venlafaxine produced results comparable to paroxetine, including superior efﬁ  cacy relative
to placebo.
(71)
A ﬁ xed-dose trial of paroxetine showed 20 mg/day to be an efﬁ  -
cacious and safe dose for the treatment of social anxiety disorder, with superior efﬁ  cacy to placebo.
(72) In a ﬂ  exible-dose trial, parox-

etine proved more efficacious than placebo after 8–12 weeks of treatment, with 55 per cent of paroxetine patients compared to 24 per cent of placebo patients identiﬁ  ed as much or very much 
improved.
(73) A double-blind discontinuation study demonstrated 
a 14 per cent relapse rate in the paroxetine group compared to a 39 per cent relapse rate in the placebo group at week 24.
(74)
Van Ameringen and colleagues(75) found sertraline to be more 
efﬁ cacious than placebo, and a 20-week double-blind discontinua-
tion trial demonstrated signiﬁ  cantly lower relapse rates for patients 
continuing on sertraline than patients switched to placebo (4 per cent versus 36 per cent, respectively).
(76) A study of ﬂ  uvoxamine 
demonstrated superior outcome, beginning at week 8, for patients receiving ﬂ  uoxamine (20 mg mean daily dose) than patients receiv-

ing placebo.
(77)
Fluoxetine has yielded less promising results and is the only 
SSRI to date that has failed to separate from placebo in controlled trials.
(65,69)  However, in one study ﬂ  uoxetine evidenced superior 
efﬁ cacy to placebo, although no differences were found between 
ﬂ uoxetine, CBGT, or their combination.(78)
(b) Benzodiazepines
Research suggests benzodiazapines have performed better than 
MAOIs and CBT in the short-term(68) and offer rapid onset of 
effect, good tolerability, and minimal side effects (e.g. sedation, withdrawal effects with abrupt discontinuation). However, benzo-diazepines are contraindicated in the presence of substance abuse and lack efﬁ  cacy for comorbid mood disorders. Clonazepam was 
shown to be efﬁ  cacious for social anxiety disorder (2–4 mg/day),

shown to be efﬁ  cacious for social anxiety disorder (2–4 mg/day), 
with patients showing improvement after 6 weeks of treatment and superior response rates compared to placebo patients at week 10.
(79) Clonazepam also produced equivalent gains to 
CBGT after 12 weeks of treatment.(80) One study of alprazolam 
demonstrated that the medication was no more efﬁ  cacious than 
placebo.(81)(c) Monoamine oxidase inhibitors
MAOIs have demonstrated efﬁ  cacy in the treatment of social anxiety 
disorder(36) similar to that of SSRIs. However, MAOI therapy 
requires strict dietary restrictions as ingesting foods rich in tyra-mine (e.g. most aged cheeses, red wine, beer) can increase the risk of rapidly escalating blood pressure. MAOIs are also associated with more adverse side effects (e.g. hypotension, sedation, weight gain, sexual dysfunction) than SSRIs. However, MAOI therapy (usually 45–90 mg/day) is justiﬁ  ed when other treatments with 
more benign side effect proﬁ  les prove ineffective.

As discussed earlier, phenelzine proved superior to placebo and 
demonstrated equivalent response rates to CBGT after 12 weeks of treatment,
(57), although CBGT evidenced more durable treatment 
gains.(62) Liebowitz and colleagues(82) found that after 8 weeks of 
acute treatment and 8 weeks of maintenance, phenelzine produced results superior to those of placebo and the ß-adreneregic blocker atenolol. Versiani and colleagues
(83) found patients who received 
phenelzine endorsed significantly greater reductions in social anxiety than placebo patients at 8 weeks. In a comparison of phenelzine, alprazolam, CBGT, and placebo with instructions for self-exposure,
(81) all groups produced relatively equivalent 
response. However, phenelzine demonstrated maintenance of gains at a 2-month follow-up, whereas alprazolam did not.
(d) Reversible inhibitors of monoamine oxidase
Moclobemide and brofaramine have been evaluated for the

Moclobemide and brofaramine have been evaluated for the 
treatment of social anxiety disorder and offer fewer side effects and dietary restrictions than MAOIs. However, moclobemide has shown modest efficacy in controlled trials and is less|efficacious than the SSRIs and MAOIs.
(36) Although brofara-
mine was found to be efficacious for social anxiety, it was never marketed.
(e) ß-adreneregic blockers
ß-adreneregic blockers (e.g. atenolol) have failed to surpass placebo in controlled trials.
(49) Propranolol appears to be efﬁ  cacious on 
an as-needed basis (10–40 mg) for anxiety related to performance situations.
(f) Buspirone
Buspirone appears no more efficacious than placebo at low dosages.
(84) One study demonstrated greater efﬁ  cacy of buspirone 
in doses greater than or equal to 45 mg/day or when used as an augmentation to an SSRI.
(85)
(g) Gabapentin and pregabalin

(85)
A single study shows some efﬁ  cacy of high doses of the anticonvul-
sant gabapentin (maximum of 3600 mg/day) in the treatment of social anxiety disorder relative to placebo.
(86) Pregabalin was also 
superior to placebo in one study,(87) but a high dose was required 
as well.
(h) Other agents
D-cycloserine, a partial adrenergic agonist associated with the facil-
itation of learning and memory consolidation, appears to enhance the efficacy of exposure. Several animal trials demonstrated enhanced fear extinction when d-cycloserine was administered prior to and after exposure trials.
(88) Similar results were shown 
when individuals receiving d-cycloserine 1 h prior to exposure demonstrated signiﬁ  cantly less social anxiety posttreatment than 
those receiving placebo.

(89)4.7.2 social anxiety disorder and specific phobias

SECTION 4  clinical syndromes of adult psychiatry 744
Integrating pharmacotherapy and cognitive 
behavioural interventions
Several studies have examined the utility of combining pharmaco-
therapy with cognitive behavioural interventions. Blomhoff and colleagues
(90) compared sertraline and pill placebo alone and in 
combination with physician-directed exposure or general medical care, which included non-directive encouragement. After 12 weeks, all active treatments surpassed pill placebo and non-directive encouragement, with sertraline and exposure proving equally efﬁ  -
cacious. Only sertraline alone or in combination with exposure proved superior to placebo at 24 weeks. However, only patients who received exposure alone demonstrated further improvement at 1-year follow-up, whereas patients receiving sertraline with or without exposure showed some degree of deterioration.
(91)
Preliminary data from a study comparing CBGT, phenelzine,

(91)
Preliminary data from a study comparing CBGT, phenelzine, 
their combination, and pill placebo, suggests phenelzine plus CBGT may be more likely to surpass placebo than either treatment alone.
(92) A similar study by Davidson and colleagues(78) found no 
advantage in combining ﬂ  uoxetine and CBGT. Preliminary data 
suggests the combination of d-cycloserine with exposure may enhance the efﬁ  cacy of exposure treatment.
(89)
Evidence for the utility of the combination of these treatments is 
mixed. T o summarize, different studies suggest that combining some medication treatments with CBT is no more efﬁ  cacious than 
either treatment alone;
(78) combining medication with CBT may 
diminish the efﬁ  cacy of CBT;(91) and combining treatments may 
show only modest benefits over the administration of either alone.
(92) The hypothesis that sequential treatments might capital-

ize on rapid medication response for faster symptom relief and cognitive behavioural treatment for superior relapse protection needs evaluation. Cognitive behavioural treatments may be utilized to help patients discontinue medical regimens after initial drug response.
Management of social anxiety disorder
(a) Treatment selection
Given the chronic nature of social anxiety disorder, CBT offers

Given the chronic nature of social anxiety disorder, CBT offers 
more enduring treatment gains compared to medication and lacks the adverse side effects. When considering cognitive behavioural interventions, it is important to assess the patient’s ability and willingness to endure exposure to anxiety-provoking situations, as exposure necessitates short-term increases in anxiety over and above what the individual may typically experience. Additionally, it is helpful to assess level of compliance with previous therapy experiences (e.g. homework compliance). Managing a patient’s treatment expectancy may further improve outcome as individuals reporting higher expectancy regarding the efﬁ  cacy of treatment 
have demonstrated greater improvement and maintenance of treatment gains.
(93)
Medication may be a preferred choice for individuals requiring

(93)
Medication may be a preferred choice for individuals requiring 
rapid response, CBT non-responders, those with a preference for medication, or those with severe social anxiety disorder and/or comorbid depression. When selecting medication treatment, it is important to consider possible side effects, the patient’s physical health, and prior medication compliance. Benzodiazepines offer rapid onset of effect, particularly beneﬁ  cial for short-term perfor-
mance situations, but their use may be contraindicated among patients with a history of alcohol or substance abuse. Given these concerns and their more benign side effect proﬁ  le, SSRIs and 
venlafaxine are best regarded as the ﬁ  rst-line medications, with the

venlafaxine are best regarded as the ﬁ  rst-line medications, with the 
benzodiazepines and MAOIs held in reserve for non-responding patients. T o date, we know little of the appropriate duration of medication treatments in social anxiety disorder, although two studies evidenced signiﬁ  cant relapse rates upon discontinuation of 
SSRIs after a total treatment period of 36–40 weeks.
(74,76)
(b) Other issues in management
Comorbid conditions should also be considered when treating social anxiety disorder with cognitive behavioural or pharmaco-logical treatments. Comorbid anxiety disorders do not appear to degrade a patient’s response to CBT; however, patients with comor-bid mood disorders may present with more severe social anxiety symptoms and, although they improve at a similar rate, require extended treatment.
(94) In general, if any comorbid condition pre-

vents the patient from engaging in exposure exercises, taking medi-cations in the prescribed manner, or complying with any other therapeutic activities, it may be necessary to treat the comorbid condition before the social anxiety disorder. In other cases, a comorbid condition might become the focus after social anxiety disorder treatment. Patients who abuse substances to ‘treat’ their social anxieties are often reticent to give up their substances before other coping strategies are made available. Ultimately, the manage-ment of comorbid conditions in individuals with social anxiety disorder depends on the analysis of the relationships between the disorders and varies from case to case.
(c) Prevention
Few studies to date have speciﬁ  cally examined ways of preventing 
social anxiety disorder; however, evidence for familial aggregation and environmental inﬂ  uence is strong. Parents may reinforce anx-

ious children for making avoidant choices.
(95) Thus, it is important 
to consider including parents of socially anxious children in treat-ment to provide parents with strategies to help their child manage the social anxiety. Parents with social anxiety disorder may also beneﬁ  t from treatment themselves.
Since social anxiety disorder has an early age of onset, treatment 
of children and adolescents should help prevent social anxiety from becoming a chronic condition. Prevention programmes have been integrated into school settings to teach children and parents coping skills (e.g. cognitive restructuring, relaxation) and instruct them on the proper conduct of exposures. Individuals in the inter-vention group have shown signiﬁ  cant improvement compared to 
non-intervention controls.
(96) Similar prevention programmes

(96) Similar prevention programmes 
have targeted at-risk youth and resulted in decreased anxiety symptoms and lower rates of anxiety disorders compared to control groups.
(97)
Informational Websites
X http://www.adaa.org/GettingHelp/AnxietyDisorders/
SocialPhobia.asp (Anxiety Disorders Association of America)
X http://www.nimh.nih.gov/HealthInformation/socialphobia-
menu.cfm (National Institute of Mental Health)
Speciﬁ  c phobia
Clinical features and functional impairment
The hallmark feature of speciﬁ  c phobia, prior to DSM-IV called 
simple phobia, is a ‘marked and persistent fear that is excessive or

745
unreasonable, cued by the presence or anticipation of a speciﬁ  c 
object or situation’ (6, p. 405). Commonly feared/avoided objects include animals, aspects of nature, or blood. Many individuals endorse some fear of these stimuli; however, in speciﬁ  c phobia, 
fear and avoidance cause significant interference with one’snormal routine, career, academic pursuits, or social activities. 
Some individuals with speciﬁ  c phobias maintain a relatively
normal routine by pursuing a lifestyle that minimizes exposureto the phobic stimulus. Often, speciﬁ  c phobias accompany a more 
impairing primary disorder that is the stimulus for seekingtreatment.
(98)
Criteria for speciﬁ  c phobia are similar between DSM-IV and ICD-
10. Both view fear as arising from exposure to a speciﬁ  c object or

(98)
10. Both view fear as arising from exposure to a speciﬁ  c object or 
situation, which leads to acute autonomic and psychological symptoms of anxiety. However, ICD-10 does not stipulatethat anxiety may be cued by the anticipation of the fearedobject or situation. Our review of speciﬁ  c phobia follows DSM 
conventions.
(b) Speciﬁ  c phobia subtypes
DSM-IV classiﬁ  es speciﬁ  c phobias into ﬁ  ve subtypes:
X animal
X natural environment
X blood-injection-injury
X situational
X other (e.g. dental/medical procedures, choking, etc.).
With the exception of blood-injection-injury phobias, expo-
sure to the phobic stimulus evokes intense anxiety that may meet criteria for a situationally-bound panic attack. Additionally, there is extreme apprehension and desire to escape or avoid the phobic stimulus.
(99) By contrast, individuals with blood-injection-injury

(99) By contrast, individuals with blood-injection-injury 
phobias exhibit a biphasic anxiety reaction (vasovagal syncope) characterized by initial, short-lived sympathetic arousal,followed by parasympathetic arousal that may result infainting.
(100) The subjective experiences of these individuals tend 
to be characterized by disgust and repulsion rather than pure apprehension.
(99)
(c) Comorbidity
The vast majority (83.4 per cent) of individuals with speciﬁ  c 
phobia experience at least one other lifetime psychiatric disorder.(19)
In the original National Comorbidity Survey, individuals with speciﬁ  c phobia were 5 times more likely to have at least one 
additional disorder than individuals who had never met criteria for a phobic disorder. In most cases, the onset of the speciﬁ  c phobia 
preceded the onset of the other disorder.
The NCS-R reported a lifetime prevalence rate of 12.5 per cent(25)

and a 12-month prevalence rate of 8.7 per cent for speciﬁ  c phobia.(20)
One study found situational/environmental phobias to be the most 
common (13.2 per cent), followed by animal phobias (7.9 per cent) and blood-injection-injury phobias (3.0 per cent).
(101)(b) Age at onset/age of treatment seeking
Age at onset of speciﬁ  c phobia tends to be earlier than other anxiety 
disorders(19,102)  and varies as a function of phobia subtype. For 
example, animal phobias onset earliest (age 7), followed by blood-injection-injury phobias (age 8), and most situational phobias (early 20s).
(103) Individuals with phobic disorders often do not seek 
treatment for 20 years after onset.(27)
(c) Gender distribution
Women receive diagnoses of speciﬁ  c phobia more often than men. 
Lifetime rates for speciﬁ  c phobia in the NCS-R were 15.7 per cent

Lifetime rates for speciﬁ  c phobia in the NCS-R were 15.7 per cent 
for women but only 6.7 per cent for men.(25) In one study, women 
reported higher rates of animal and situational/environmental phobias, but rates of blood-injection-injury phobia did not differ.
(101)
Aetiology of speciﬁ  c phobia
There is considerable evidence for familial/genetic transmission of 
speciﬁ  c phobia.(32,104) In one study, 31 per cent of ﬁ  rst-degree rela-
tives of persons with speciﬁ  c phobia also met criteria for speciﬁ  c 
phobia.(104) Rates of speciﬁ  c phobia were higher among ﬁ  rst-degree 
relatives of persons with speciﬁ  c phobia and no other anxiety dis-
order than among ﬁ  rst-degree relatives of persons who were never 
mentally ill.(105) In the Virginia Twin Study,(32) concordance rates

mentally ill.(105) In the Virginia Twin Study,(32) concordance rates 
for animal phobia were 25.9 and 11.0 per cent among monozygotic and dizygotic twins, respectively. Concordance rates for situational phobia were similar in monozygotic and dizygotic twins. Moreover, children classiﬁ  ed as behaviourally inhibited have shown higher 
risk for the development of multiple speciﬁ  c phobias.
(106)
Classical conditioning theory(107) holds that phobias are learned 
through the association of negative experience with an object or situation. However, individuals with more previous non-traumatic experiences with the object or situation are less likely to develop a phobia upon a negative encounter than those with less prior expe-rience when traumatized. Two-factor learning theory
(108) intro-

duced avoidance as a critical component to the maintenance of anxiety. That is, responses of avoidance or escape are learned and serve to decrease the discomfort arising from exposure to condi-tioned stimuli. Repeated negative reinforcement of avoidance behaviour (i.e. reduction of arousal on removal of oneself from proximity to the phobic object or situation) maintains the fear and makes it resistant to extinction.
Some conditioning theorists assert that feared stimuli are not 
randomly determined; rather, humans have inherited a predisposi-tion to fear speciﬁ  c stimuli through natural selection. Marks’
(109)
‘preparedness’ theory maintains that commonly feared objects 
are those that historically threatened the survival of the individual or the species. In this model, phobias are viewed as instances of ‘prepared learning’ , which is selective, easily acquired, difﬁ  cult to 
extinguish, and non-cognitive.
(110) However, a large number of

(110) However, a large number of 
studies also suggest that phobias may be acquired via observational and informational learning (e.g. hearing that the situation is dangerous).
Course of speciﬁ  c phobia
Individuals with speciﬁ  c phobias acquire their fear(s) early in 
life, and the disorder tends to be chronic or recurrent without treatment.
(111) Often individuals with speciﬁ  c phobias adapt their 
lifestyle to avoid contact with the feared stimuli, such that only 4.7.2 social anxiety disorder and specific phobias

SECTION 4  clinical syndromes of adult psychiatry 746
persons with the most severe speciﬁ  c phobias seek treatment. 
Events that commonly precipitate treatment seeking include a change in lifestyle that increases exposure to the feared stimulus (e.g. change in occupation that requires frequent air travel) or the experience of a panic attack in anticipation or in the presence of the feared stimulus.
(i) Exposure
Prolonged and repeated in vivo  exposure to feared stimuli is by far 
the most studied and efﬁ  cacious intervention for speciﬁ  c pho-
bia(112) and should be considered the ﬁ  rst-line treatment. Although 
in vivo  exposure is generally believed to be more efﬁ  cacious than 
imaginal exposure for speciﬁ  c phobia, some studies found in vivo
and imaginal exposure techniques to be similarly efﬁ  cacious.(113)
Modelling in the form of observing another patient receive treat-

ment has been shown to enhance the effects of exposure and to increase the speed at which positive outcomes are attained.
(114)
Multiple exposures sessions are considered more efficacious than one session, although some studies report positive outcomes for one-session treatments.
(115) Further, one-session group in vivo
exposure treatment has produced gains similar to those of one-session individual in vivo  exposure treatment.
(115) Variations in 
spacing of exposure sessions (e.g. 10 daily versus 10 weekly) have shown equivalent outcomes.
(116) Finally, therapist-directed treat-
ments have generally been more efﬁ  cacious than self-directed treat-
ments,(117) with gains enduring up to 8 years.(114) When possible, 
exposures should be conducted in a variety of settings to enhance generalization outside the therapeutic setting.
(54)

(54)
In vivo  exposure situations can sometimes be difﬁ  cult to arrange 
and imaginal exposure may not achieve the reality or intensity needed to elicit an anxiety response. In such instances, virtual reality exposure ( VRE ), in which feared situations are presented in three 
dimensional simulations, may greatly enhance the efﬁ  cacy of expo-
sures. The salience of virtual environments can be augmented by instructing patients to touch real objects (e.g. toy spiders) which correspond with the virtual environment. Recent case studies demonstrated the efﬁ  cacy of VRE either alone
(118,119)  or in combi-
nation with anxiety management training.(120) In a controlled trial 
for fear of ﬂ  ying, VRE training showed equivalent gains to in vivo 
exposure at 6 and 12-month follow-up(121). Another study indi-

cated that VRE produced superior gains to an attention placebo therapy, although gains were not maintained at 6-month follow-up.
(122) D-cycloserine in combination with VRE has also 
shown enhanced treatment efﬁ  cacy over VRE with placebo.(123)
(b) Applied relaxation and applied tension
Applied relaxation  combines focused attention on different muscle 
groups while tensing and relaxing muscles,(124) with instruction 
to practice these skills ﬁ  rst in non-anxiety-provoking situations 
and then in anxiety-provoking situations.(125) Although research 
is limited, applied relaxation has demonstrated efﬁ  cacy,(126) espe-
cially among patients with higher levels of physiological reactivity than behavioural avoidance. Applied tension , designed speciﬁ  cally 
for blood-injection-injury phobia to treat parasympathetic arousal,

for blood-injection-injury phobia to treat parasympathetic arousal, 
requires the patient to tense different muscle groups in the pres-
ence of phobic stimuli to elevate blood pressure. Persons with phobias for blood, wounds, and injuries responded equally well to applied tension, applied relaxation, or their combination
(127)
Individuals treated with applied tension also evidenced greater 
treatment gains posttreatment and at 1-year follow-up than those treated with in vivo  exposure alone.
(128) In one dismantling study, 
individuals treated with applied tension and tension only (without the exposure component) evidenced equivalent gains and main-tained superior outcomes at posttreatment and 1-year follow-up compared to patients who received in vivo  exposure.
(129)
(c) Cognitive restructuring
Phobia-speciﬁ  c irrational thoughts may contribute to the develop-
ment of the phobia, maintain avoidance behaviour, and contribute to physiological symptoms.

(129)
(130) When combined with exposure to 
feared stimuli, cognitive restructuring has proven efﬁ  cacious,(131)
although there are relatively few studies of cognitively-oriented 
treatments for speciﬁ  c phobia.
Drug treatments for speciﬁ  c phobia have consistently been shown 
to be less efﬁ  cacious than behavioural treatments and may hinder 
maintenance of treatment gains. ß-Adrenergic blockers reduce some symptoms of sympathetic arousal during exposure to feared stimuli but fail to decrease subjective fear.
(132) Although benzodi-
azepines (e.g. diazepam) may facilitate approach to feared stimuli, they may also reduce the efﬁ  cacy of behaviour therapies by inhibit-
ing the experience of anxiety during exposure.
(133) Recent studies

(133) Recent studies 
suggest d-cycloserine may facilitate exposure and extinction to spe-ciﬁ c feared stimuli. In a study of acrophobia patients, d-cycloserine 
was administered prior to exposure sessions and proved superior to placebo in reducing anxiety symptoms.
(123)
Management of speciﬁ  c phobia
Exposure is clearly the treatment of choice for speciﬁ  c phobia, 
although facing feared stimuli may be particularly challenging for some patients, and their willingness and ability to participate in exposures should be assessed prior to treatment. Tailoring treat-ment to individual response patterns may improve outcome. For instance, patients with heightened physiological reactivity may respond preferentially to applied relaxation, whereas patients show-ing avoidance behaviour may respond better to in vivo
exposure.
(126) Further, individuals who experience anxiety primar-

exposure.
ily in the form of anxious thoughts may respond better to cognitive techniques.
(134)
For patients unwilling or unable to engage in cognitive behavioural 
interventions, medication may be an appropriate alternative. However, it is ﬁ  rst important to educate patients about the possi-
bility of dependence with regular use and the side effects of high doses (e.g. sedation). If the patient is participating in exposure therapy, it is also necessary to explain that medication may inter-fere with the efﬁ  cacy of exposure treatment.
(b) Prevention
Children with speciﬁ  c phobia were included in the Queensland 
Early Intervention and Prevention of Anxiety Project, but no other preventive efforts have been mounted. It is tempting to speculate that children could be ‘inoculated’ against a variety of the more common speciﬁ  c phobias by systematic exposure to potentially 
feared objects or situations.

747
http://www.adaa.org/GettingHelp/AnxietyDisorders/Speciﬁ  cPhobia.asp 
(Anxiety Disorders Association of America)
http://www.mentalhealthamerica.net/go/phobias (Mental Health America)
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SECTION 4  clinical syndromes of adult psychiatry 750
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4.7.3 Panic disorder 
and agoraphobia
Panic disorder draws its name from the Greek god Pan, god of 
flocks. Pan was known for suddenly frightening animals and humans ‘out of the blue’ . The spontaneous ‘out of the blue’ character of panic attacks is the principal identifying characteristic of panic disorder and central to its recognition and diagnosis.
We know the syndrome that we currently call panic disorder with

We know the syndrome that we currently call panic disorder with 
and without agoraphobia has probably existed since the beginning of recorded history. Hippocrates presented cases of obvious phobic avoidance around 400 bc.
(1) One of the ﬁ  rst modern descriptions 
was by Benedikt around 1870, describing individuals who devel-oped sudden anxiety and dizziness in public places.
(2)
Certainly, our current modern ideas of panic disorder evolved 
essentially simultaneously in the United States and Europe in the early to mid-1960s. Donald Klein in the United States described in 1964 the panic syndrome and reported that it was responsive to imipramine.
(3) Isaac Marks in the United Kingdom also described panic attacks and agoraphobic avoidance, and treating the 
syndrome effectively with behaviour therapy.(4)
Until the last several decades, panic disorder and agoraphobia

Until the last several decades, panic disorder and agoraphobia 
were actually thought to be rare syndromes. It is now clear that individuals with these difﬁ  culties are anything but rare. In fact, 
panic disorder is one of the most common presenting problems in individuals seeking mental health treatment and the ﬁ  fth most 
common problem seen in primary care settings.
(5) It was thought 
to be a mild problem, but we now know that it is associated with signiﬁ  cant dysfunction. The disability in social, occupational, and 
family life is in fact comparable to major depression.
Although there are differences in the understandings of panic 
disorder and its treatments across the world, this chapter will review the current understanding about panic disorder, its charac-teristics, diagnosis, aetiology, and treatments.

One of the earliest and most accurate descriptions of panic attacks was provided by Charles Darwin in 1872 as he described his own episodes:
The heartbeats quickly and violently so that it palpitates and knocks against the ribs . . . the skin instantly becomes pale as during incipient faintness . . . under a sense of great fear . . . in connection with the disturbed action of the heart, the breathing is hurried . . . one of the best marked symptoms is the trembling of all the muscles of the body.
(6)
The most characteristic type of panic attack is the spontaneous

(6)
The most characteristic type of panic attack is the spontaneous 
‘out of the blue’ episode of extreme anxiety. Other ‘situational panic attacks’ occur immediately upon exposure, or in anticipation of exposure to particular situations, usually where panic attacks have occurred previously. Some individuals have panic attacks in certain situations some of the time, but not always, and these are labelled ‘situationally predisposed panic attacks’ .
Panic attacks also occur in other anxiety syndromes and are more 
or less the same in whatever syndrome where they occur. However, spontaneous panic attacks in panic disorder tend to have more dizziness, paraesthesia, shaking, chest pain, and fears of going mad. Shortness of breath is more common in panic attacks in agoraphobia. Certainly blushing is particularly characteristic of panic attacks in social phobia.
The symptoms of panic attacks in order of their frequency

The symptoms of panic attacks in order of their frequency 
include palpitations, pounding heart, tachycardia, sweating, trem-bling or shaking, shortness of breath or smothering, feeling of choking, chest pain or discomfort, nausea or abdominal distress, feeling dizzy, unsteady, lightheaded or faint, derealization or deper-sonalization, fear of losing control or going mad, fear of dying, paraesthesia, and chills or hot ﬂ  ushes.
Panic attacks by deﬁ  nition generally involve four or more of the

Panic attacks by deﬁ  nition generally involve four or more of the 
above symptoms to meet diagnostic criteria for panic disorder in the DSM-IV . The anxiety is crescendo in nature, building to a peak in 10 min in most cases. Panic attacks usually last for several minutes, but in some patients they can last for hours. The frequency and sever-ity of panic attacks varies greatly between individuals and, at times, in individuals. Some have only one to three panic attacks per year, whereas others may have multiple panic attacks each day. Some indi-viduals have bursts of panic attacks and then an absence of all attacks for a period of time. Across a large panic disorder clinical trial, the typical patient described one to two panic attacks per week.
(7)

751
Panic attacks with fewer than four symptoms have been labelled 
‘limited-symptom attacks’ or ‘little panic attacks’ , and most indi-viduals with panic disorder have these, as well as panic attacks with four or more symptoms. The threshold of four symptoms was chosen for DSM-IV because individuals with panic attacks with four symptoms or more had more disability than patients with one- to three-symptom attacks. This threshold is clearly arbitrary, and patients having panic attacks with fewer symptoms do have signiﬁ  cant morbidity.
Panic attacks are extremely frightening and patients develop an

Panic attacks are extremely frightening and patients develop an 
essentially logical fear of having more panic attacks. Patients develop worry and anxiety about the possibility of panic attacks recurring. This anxiety between attacks has been called ‘anticipatory anxiety’ and can be almost constant, and characteristically increases prior to exposure to situations previously associated with panic attacks (e.g. having to shop in the supermarket where a panic attack has occurred).
A signiﬁ  cant number of people with panic attacks go on to 
develop fear and avoidance of situations associated with previous panic attacks. They also fear situations where escape would be difﬁ cult or embarrassing, or where help might not be available. 
Most patients mistakenly believe they become incapacitated
and incapable of taking care of themselves during a panic attack

and incapable of taking care of themselves during a panic attack 
and therefore, many go on to develop avoidance of a variety of situations where they could not easily get help. Factor analytical studies demonstrate that there are clusters of situations associated with avoidance. These typically include public transportation(e.g. buses, trains, planes), riding in or driving a car, especially on heavily travelled roads, crowds (e.g. the cinema, a football match, large shopping centres), shopping (especially in supermarkets), particularly where one must stand in queues, and bridges, tunnels, elevators, and other enclosed spaces.
(8) In the event of a panic 
attack, people often have an overwhelming need to escape or return to a place of safety such as home. Therefore they fear situa-tions where escape is difﬁ  cult or impossible, e.g. airplanes, trafﬁ  c

jams on a bridge, dental appointments, etc. On closer examina-tion, it is clear that patients do not actually fear the situationitself but rather reason ‘what if’ the panic feelings occur whilein that situation. This has led to the syndrome being called the ‘what if’ syndrome, emphasizing that there is actually a ‘fear ofthe fear’ .
(9)
Patients tend to avoid such situations or force themselves to 
endure them in distress or take a companion along ‘to help’ . Others limit their travel to short distances from home or take longer routes where they perceive help would be available (e.g. police, doctors’ ofﬁ ces, ﬁ  re stations, etc).
Some patients develop agoraphobic avoidance following their 
ﬁ rst attack, some only after frequent and severe attacks, and some

ﬁ rst attack, some only after frequent and severe attacks, and some 
never develop agoraphobic avoidance. In community samples, one-third to half of patients who meet criteria for panic disorder also has significant agoraphobic avoidance. The rate is higher (75 per cent) in most clinical samples. A minority (5 per cent) ulti-mately become unable to leave their homes and are housebound.
Many patients have panic attacks that awaken them from sleep 
(nocturnal panic attacks), as well as during the day. These are in 
fact quite common and the majority of panic disorder patients 
experience them. These occur during slow wave sleep early in sleep. These panic attacks are essentially identical to traditional panic attacks that occur during the day. There is a group of patients who have what are called non-fearful panic attacks. These involve the

sudden onset of physiological symptoms without the cognitive components of fear or anxiety. These primarily are medical patients, usually cardiac, who might have episodes of sudden tachycardia and palpitations but no fear.
(10)
The earliest modern accounts of what is almost certainly the 
panic disorder syndrome began appearing in the mid-1900s. There were accounts beginning in 1866 of paroxysmal anxiety episodes that did not use the term ‘panic attack’ . During the American Civil War, patients were diagnosed with ‘irritableheart syndrome’ or ‘Da Costa syndrome’ (1871) with clear descriptions of what we now know as panic disorder. Westphalin Germany in 1872 clearly described patients having panic attacks and agoraphobic avoidance of wide open spaces.
(11)
Again, in the First World War (1918) the syndrome ‘neurocircu-latory asthenia’ was described which had most of the featuresof panic disorder.
It was, in fact, Freud in Case IV of Katharina, published in

It was, in fact, Freud in Case IV of Katharina, published in 
1895, who set the background for the modern classiﬁ  cation of 
panic disorder. However, it was the Feighner criteria published in the United States in 1972 that give the ﬁ  rst formal diagnostic rec-
ognition to the syndrome.
(12) The Research Diagnostic Criteria 
(RDC) which followed in 1978 ﬁ  rst split panic disorder away 
from what we now call generalized anxiety disorder (GAD).In the RDC, panic disorder had panic attacks while GAD did not. These diagnoses were made part of the DSM-III diagnostic scheme in 1980.
It was the conceptualization of panic disorder by Donald Klein 
in 1964 in the United States that led to the predominant view of the syndrome, certainly in the United States.
(13) Klein argued that

(13) Klein argued that 
panic attacks were the core of the syndrome, and the remaining clinical phenomena were consequences of the panic attacks. He conceptualized that anticipatory anxiety was the fear of the possible recurrence of panic attacks, and similarly that agorapho-bia was the subsequent fear and avoidance of situations where panic attacks had occurred. The bringing together of these three phenomena into one concept was accepted in the DSM-IIIR, and more recently in the DSM-IV in the United States.
(14)
The biological ﬁ  ndings that typical panic attacks could be elicited 
in panic disorder patients with infusions of lactate, doses of caffeine, or breathing 35 per cent CO
2 supported this conceptual-

ization of the syndrome as primarily centered around panic attacks. This hypothesis was further supported by epidemiological ﬁ  ndings 
of essentially the same illness around the world.
However, this idea remains controversial across the different 
sides of the Atlantic. The American DSM-IIIR and DSM-IV diag-nostic schema continue to utilize the idea that panic attacks are pre-eminent and created two diagnoses: panic disorder and panic disorder with agoraphobia. In Europe and in the ICD-10, agora-phobia is conceptualized as dominant over panic attacks. Therefore, when agoraphobia and panic attacks are both present, the diagno-sis is conceptualized as a phobia and that condition is diagnosed as agoraphobia with panic attacks. Beyond this theoretical debate is the clinical question whether the treatment should be aimed ﬁ  rst at

panic attacks (in the United States concept) or at agoraphobic 
avoidance, for example with exposure therapy (in the European schema).4.7.3 panic disorder and agoraphobia

SECTION 4  clinical syndromes of adult psychiatry 752
(a) Diagnosis
The most recently revised diagnostic schema for this syndrome is 
the DSM-IV . Changes from the DSM-IIIR were made based on two principles:
1 any new empirical data that required changes be made;
2 an attempt to make the DSM-IV and ICD-10 more compatible.
For the diagnoses of panic disorder and agoraphobia, an attempt 
was also made to more nearly describe the prototypic patient and to move away from the pseudoquantiﬁ  cation of using number of 
panic attacks per week.
(14)
The DSM-IV clariﬁ  ed that panic attacks occurred in multiple 
syndromes including social phobia, obsessive–compulsivedisorder, depression, and others. However, DSM-IV utilized thedistinction that only in panic disorder were there recurrentspontaneous panic attacks not bound to any particular situation. The diagnosis of panic disorder has several requirements includ-ing the following:
X Recurrent, unexpected panic attacks (situational panic attacks

X Recurrent, unexpected panic attacks (situational panic attacks 
could also occur but there would need to be at least two unex-pected panic attacks by history).
X Panic attacks needed to be followed by at least 1 month of persis-
tent anxiety about potential recurrence of further panic attacks, implications of these attacks (e.g. going mad, something wrong medically), or a signiﬁ  cant behavioural change because of these 
attacks. This was necessary because some patients had panic attacks and completely changed their lives but denied that they were worried about experiencing more panic attacks or the implications of the panic attacks.
(14)
The agoraphobia criteria remained largely unchanged, but it was 
made more clear that the diagnosis was based on persistent fear and avoidance of certain clusters of situations and listed the most common.
The controversial diagnosis of agoraphobia without a history

The controversial diagnosis of agoraphobia without a history 
of panic disorder was retained until further clarificationis obtained through research. Our current understanding isthat these patients generally have never fully met criteria for panic disorder because their panic-like symptoms have notmet the diagnostic criterion requiring four full symptoms for a panic attack. Available research suggests that these patients are otherwise very much like typical patients with panic disorder and agoraphobia. Some patients actually have only one or two symptoms (e.g. fear of loss of bladder or bowel control or only 
tachycardia).
Perhaps the most difﬁ  cult diagnostic issue is the frequent comor-
bidity. The Epidemiologic Catchment Area study documented that approximately 50 per cent of panic disorder patients over their life-time have another anxiety disorder.
(15)
In actuality, depression is more commonly comorbid with

(15)
In actuality, depression is more commonly comorbid with 
panic disorder than even agoraphobia and suggests a close rela-tionship between these syndromes. Comorbid depression ranged from 22.5 to 68.2 per cent in various samples. Lifetime rates vary from 35 to 91 per cent.
(16) Although approximately half the 
patients developed panic disorder and depression at essentially the same time, one-quarter develop depression before panicdisorder and one-quarter panic disorder before depression.
(17)
Surprisingly, bipolar illness has been reported to be as high as 20.8 per cent.Easily one-third of panic disorder patients abuse alcohol. The 
percentage in clinical samples is much higher with 13 to 43 per cent of panic disorder patients also meeting criteria for alcoholism.
(18)
(b) Differential diagnosis

(18)
It is particularly important to determine whether agoraphobic avoidance is present, because its treatment usually requires some sort of exposure therapy. Patients will often not volunteer that they are avoiding certain situations out of embarrassment. As men-tioned earlier, depression and panic disorder often occur together and again patients often do not describe the other syndrome, but rather describe the syndrome which is most painful to them at that time. However, proper recognition of comorbid depression is especially important because of the marked increase (four-fold) in suicide attempts in patients with panic disorder and depression.
The difference between panic disorder and GAD depends on

The difference between panic disorder and GAD depends on 
whether patients have panic attacks and whether they have multi-ple, unrealistic, and excessive worries about most aspects of life, not just panic attacks. These worries in GAD often concern money, 
health, children, work problems, etc. The differential with social 
phobia centres on whether the anxiety is conﬁ  ned entirely towards 
social situations where the individual fears embarrassment and humiliation. Speciﬁ  c phobias involve panic attacks, but they occur 
in very speciﬁ  c situations (e.g. high places, thunderstorms) or in 
the presence of speciﬁ  c objects (e.g. animals, snakes). The post-
traumatic stress disorder patient may have many panic-like symp-toms, but their illness begins quite speciﬁ  cally after a traumatic

traumatic stress disorder patient may have many panic-like symp-toms, but their illness begins quite speciﬁ  cally after a traumatic 
experience and anxiety is associated with reminders of that trauma. Finally, obsessive–compulsive disorder can involve panic attacks but only in the speciﬁ  c context of obsessional concerns (e.g. con-
tamination, etc.). In these patients, panic attacks are also dwarfed in importance by typical obsessions and compulsions/rituals con-cerning contamination, symmetry, bad events, etc.
(c) Medical conditions

Panic-like symptoms do occur in various medical conditions (hyperthyroidism, phaeochromocytoma, hyperparathyroidism, seizures, cardiac arrhythmias, especially supraventricular tachy-cardia, inner ear difficulties, chronic obstructive pulmonary disease, use of marijuana, withdrawal from drugs of abuse, and over the counter drugs containing caffeine or pseudoephedrine) (Table 4.7.3.1). Also, the typical panic disorder patient does report a large number of physical symptoms and usually to a non-psychiatric physician.
As mentioned, there are medical conditions that can mimic panic 
disorder (Table 4.7.3.1). There is also evidence that there are slightly increased rates of certain illnesses, for example hyperthyroidism (11–13 per cent) and perhaps mitral valve prolapse. However, these are uncommon in panic disorder patients. Most experts recom-
mend a relatively conservative diagnostic medical work-up.

mend a relatively conservative diagnostic medical work-up. 
Generally, the most valuable part of a medical examination is a careful history with follow-up of any strongly suggested possibili-ties, supplemented by a few laboratory tests (complete blood count, thyroid function tests, metabolic screen, and ECG, especially if the patient is over 40 years of age).
(d) Panic disorder in the general medical setting
Conservative estimates of panic disorder in primary care have ranged from 3 to 8 per cent with at least 50 per cent going unrecog-nized.
(19) The average panic disorder patient in general medicine

753
takes 10 years or more for a correct diagnosis to be made with an 
escalation of the use of health care services over this period. In gen-eral, the presence of panic disorder leads to a three-fold increase in utilization of general medical services.
The percentage of panic disorder patients is also markedly higher 
in certain medical groups. These include the very prevalent but most difﬁ  cult to diagnose patients with vague symptoms such 
as fatigue, back pain, headache, dizziness, chest pain, etc.
(20) or 
multiple symptoms (more than ﬁ  ve).(21)
In a classic study of unrecognized panic disorder patients 
who were referred for a psychiatric consultation from primary care, 39 per cent had cardiovascular symptoms, 33 per cent gastrointes-tinal symptoms, and 44 per cent neurological.
(22) It is now clear

(22) It is now clear 
that 16 to 25 per cent of patients presenting to the emergency room with chest pain have panic disorder. Fully 25 per cent of cardiology practice involves panic disorder, usually unrecognized with 80 per cent of patients with chest pain and normal angiograms ultimately diagnosed with panic disorder. We could also increase our yield of recognizing panic disorder patients in certain procedure-oriented situations. For instance, 28 per cent of patients referred for Holter monitoring for palpitations have panic disorder, as do 66 per cent of patients undergoing a work-up to rule out phaeochromocytoma.
(23)
Also, 44 per cent of irritable bowel syndrome and 15 per cent of patients with headache symptoms seeing a physician have panic disorder, and these are both very prevalent disorders.
Recent studies document that treatment of panic disorder in the 
medical setting when diagnosed there is most cost-effective.
(e) Comment

A recent large study sponsored by the World Health Organization (WHO) studied primary care patients in 14 different countries.
(19)
Of patients in that study who had a single panic attack in the previ-ous month, 99 per cent had an anxiety disorder or depression, or a subthreshold anxiety disorder or depressive disorder. The occur-rence of a single panic attack also predicted the onset of panic disorder in two-thirds of the patients studied in the next year, a

four-fold increase in depression (51 per cent) in the next year, and marked increases in alcoholism, social phobia, and obsessive–compulsive disorder. It would appear that the occurrence of even a single panic attack may well represent the ‘tip of the iceberg’ and should serve as a signal for increased scrutiny for anxiety and depressive syndromes. This has been recently replicated in a large (N = 3021) European sample.
(24)
Surveys largely utilizing DSM diagnoses have found wide agree-
ment and generally equal prevalence’s of panic disorder across many countries.
(16,25)  Utilizing speciﬁ  c criteria for panic attacks, 
prevalence for panic attacks has generally averaged 7 to 9 per cent of the population (range 1.8–22.7 per cent). However, if criteria for panic attacks are liberalized somewhat (‘fearful spells’) in terms of the number of times and severity, the prevalence doubles.
There is a striking uniformity worldwide for the observed preva-

lence of panic disorder. In 10 community studies involving over 40 000 subjects, the majority of studies found lifetime prevalence rates for panic disorder averaging 1.5 to 3.7 per cent, with a yearly prevalence of around 1 and 1.1 per cent of panic disorder with ago-raphobia (lifetime).
(25) In clinical samples there is greater variabil-
ity. In the previously mentioned WHO survey of 14 countries, the prevalence for panic disorder in primary care ranged from a low of 1.4 per cent to a high of 16.5 per cent for panic attacks and 0 to 3.5 per cent for panic disorder itself.
(19) The average was 1.1 per 
cent (currently) and 3.5 per cent (lifetime), which is surprisingly similar to the community samples. As mentioned, rates are much higher in specialized medical clinics and range from 15 per cent in dizziness clinics, to 16 to 65 per cent in cardiology practices, to 35 per cent in hyperventilation clinics, etc.

Panic disorder has been uniformly observed to be at least two times more prevalent in females than males.
(25) The Epidemiologic 
Catchment Area study demonstrated a prevalence of 3:2. In clinical samples it is generally 3:1. The onset of panic disorder appears to fall into two peaks. The ﬁ  rst occurs in the early to mid-twenties 
(15–24 years old) with a second peak at 45–54 years of age. The onset of panic disorder after the age of 65 is rare (0.1 per cent).
The highest rates of panic disorder and agoraphobia occur in

The highest rates of panic disorder and agoraphobia occur in 
widowed, divorced, or separated individuals living in cities. Limited education, early parental loss, and physical or sexual abuse are also risk factors. Agoraphobia is clearly more prevalent in females, and females make up three-quarters of the sample with extensive avoidance. Males tend to have longer duration of illness but less agoraphobia and depression, and less frequent help seeking. Perhaps the greater necessity to perform in the workplace retards 
avoidance in males.
Aetiology
Genetic predisposition
Certainly the preponderance of evidence suggests there is a genetic

Aetiology
Certainly the preponderance of evidence suggests there is a genetic 
contribution to the predisposition to develop panic attacks and agoraphobia. There are increased rates of panic disorder inﬁ rst-degree relatives ranging from 2- to 20-fold with the median Table 4.7.3.1  Medical conditions that produce panic-like symptoms
Endocrine Respiratory
Hyperthyroidism Chronic obstructiveHypoparathyroidism  pulmonary diseaseHypoglycaemia AsthmaPhaeochromacytoma Substance-induced
Carcinoid syndrome CaffeineCushing’s disease Cocaine
Cardiovascular Marijuana
Arrhythmias (supraventricular) TheophyllineAtypical chest pain AmphetaminesMitral valve prolapse SteroidsNeurological Alcohol/sedative
Seizures  withdrawalVestibular disease Haematological
Anaemia4.7.3 panic disorder and agoraphobia

SECTION 4  clinical syndromes of adult psychiatry 754
seven- to eight-fold. Overall, studies suggest that another affected 
relative can be found 25 to 50 per cent of the time, two times as often in female relatives. The increased familial aggregation is spe-ciﬁ c for panic disorder. These ﬁ  ndings are certainly consistent with 
a modest genetic transmission with relatively high speciﬁ  city.
Although twin studies are limited, T orgersen
(26) did find 
increased concordance in monozygotic twins (31 versus 0 per cent). In the largest sample of interviewed female twins, a several-fold increase was again found (23.9 versus 10.9 per cent).
(27) Skre et al.(28)
found a two-fold increase of panic disorder in monozygotic twins, 
while other studies fail to ﬁ  nd an increased incidence.
Overall, evidence from family and twin studies suggests that

Overall, evidence from family and twin studies suggests that 
panic disorder involves modest inheritability of around 30 to 40 per cent. The best model suggests 50 per cent genetic and 50 per cent environmental inﬂ  uences. Recent linkage studies to conﬁ  rm 
these hypotheses have been contradictory (e.g. with angiotensin, brain-derived neurotropic factor) but do suggest that single-gene transmission is unlikely. However, research is active in this area with positive replicated linkages with chromosomes 13q, 22q, 7p, and 9q31. Identiﬁ  ed candidate genes include the ADOR2A, 10832/T, 
CCK genes, and genes coding for the 5HT1A, 5HT2A, and COMT 
genes and there is evidence of a link to the corticotrophin releasing 
hormone gene.
(29) This leaves the possibilities of either heterogene-
ity across families and/or a polygenic inheritance.(30)

Several converging lines do link childhood anxiety with adult 
anxiety, consistent with a genetic predisposition. This is particu-larly true for separation anxiety in children. Kagan et al .
(31) have 
prescribed that 10 per cent of Caucasian children are born with heightened anxiety which they call behavioural inhibition. Behavioural inhibition is higher in children of anxiety-disordered parents, and there are high rates of anxiety disorders in children of 
adults with panic disorder. As behaviourally inhibited children have matured, they have been found to show higher rates of anxiety 
and phobic disorders.
(32) Currently, this is probably the best model

(32) Currently, this is probably the best model 
of an inherited anxiety predisposition. A variant of this type model proposes that there is an aethological factor involving an evolu-tionarily determined vulnerability to unfamiliar territory. This might explain why the seemingly inherited anxiety is to speciﬁ  c 
situations. This is also consistent with the high rate of precipitating events prior to the onset of clinical difﬁ  culties. In this model an 
evolutionarily/genetically determined vulnerability would be clini-cally ‘activated’ by critical stressors.
Precipitating events have been reported in 60 to 96 per cent of 
cases. These have often centred on separation or loss, relationship difﬁ culties, taking on new responsibility, and physiological stress-
ors (e.g. childbirth, surgery, hyperthyroidism).
(33) This is certainly 
consistent with a diathesis/vulnerability model with the illness being precipitated in a predisposed individual in adulthood.

There are also many studies suggesting that traumatic early 
events may ﬁ  gure in the vulnerability leading to panic disorder. 
The majority of children in some studies have experienced early 
parental separation. A traumatic event in childhood has been 
retrospectively reported in at least two-thirds of individuals, a three-fold increase.
(34) The most common adult disorder following 
sexual abuse before the age of ﬁ  ve is in fact a 44 per cent incidence 
of agoraphobia.(35)
There is some evidence in a prospective study involving over 
3000 individuals that dependent personality traits were later
associated with the development of anxiety disorders. There are also retrospective data that adult panic disorder patients describe

associated with the development of anxiety disorders. There are also retrospective data that adult panic disorder patients describe 
their parents as being overly protective and less caring. It is difﬁ  cult 
to separate the effects on individuals of the anxiety disorders them-selves which create dependent behaviour, or overprotectiveness in the parents producing dependent personality traits.
Biological models
(a) Noradrenaline
There is considerable evidence implicating the brain noradrenaline (norepinephrine) brain systems and panic disorder. The noradren-ergic agents yohimbine and isoproterenol stimulate panic attacks in panic disorder patients, suggesting a possible subsensitivity of pre-synaptic alpha 2 inhibitory adrenoreceptors. Both these drugs increase the ﬁ  ring rate of the locus ceruleus, generally thought to

be part of the brain anxiety circuit. It is also true that most effective medications in the treatment of panic disorder in fact decrease locus ceruleus ﬁ  ring rate and most panicogenic stimuli increase the 
locus ceruleus ﬁ  ring rate.
(b) Serotonin (5HT)
Findings with 5HT brain systems in panic disorder are contradic-
tory, probably because of the different 5HT circuits and receptors in different areas of the brain. Most investigators believe, however, that an increase in 5HT transmission decreases panic disorder perhaps because 5HT neurones in ventrolateral periaqueductal grey appear to inhibit sympathoexcitation and the ﬁ  ght or ﬂ  ight 
response in the rat.
(36) The principal human evidence for 5HT 
being central in panic is that the selective serotonin reuptake inhib-itors are effective and that they increase 5HT transmission after long-term use. Also, rapid depletion of 5HT has been shown to result in an increase in panic responses to ﬂ  umazenil. Whether this

increased neurotramsmission in fact leads to downregulation of a supersensitive post-synaptic receptor is one logical possibility, but is as yet unproven. These theories received recent support from PET scan studies demonstrating reductions in brain 5HT1A receptors
(37) and 5HT transporter binding.(38)
(c) γ-Aminobutyric acid
The γ-aminobutyric acid (GABA) system is almost certainly 
involved in panic disorder with perhaps the strongest evidence being that benzodiazepine agonists such as alprazolam and clonaz-epam are clearly effective treatments for panic disorder. Also GABA antagonists such as ﬂ  umezanil have panicogenic effects in panic 
disorder patients, and reverse benzodiazepine agonists such as β-carbolines can cause panic attacks. There is an impaired GABA

disorder patients, and reverse benzodiazepine agonists such as β-carbolines can cause panic attacks. There is an impaired GABA 
neuronal response to benzodiazepines (BZs) on brain magnetic spectroscopy and decreased GABA levels in the cingulate and basal ganglia, also on magnetic spectroscopy. Also, positron emission tomography data have demonstrated decreased benzodiazepine binding in the inferior brain areas, including the inferior parieto-temporo-occipital areas.
(d) Cholecystokinin–pentagastrin
Cholecystokinin is clearly involved in anxiety in animals. Also, panic disorder patients develop panic attacks in a dose-dependent fashion with administration of pentagastrin. However, cholecysto-kinin antagonists have not yet been shown to be effective in humans.
Recent genetic studies implicate CCK gene polymorphisms in 
panic disorder.

755
(e) Brain imaging
The explosion of brain imaging data demonstrating a brain 
circuit for fear and anxiety involving the extended amygdala circuit (amygdala, hippocampus, periaqueductal grey, locus coeruleus, thalamus, cingulate, and orbitofrontal areas) has lead to the hypoth-eses that it is this circuit which is abnormally active in panic disor-der.
(39)
(f) Psychological factors
Many critics disagree with the importance of biological ﬁ  ndings in 
panic disorder, principally, various European workers and the cog-nitive theorists. They argue that panic attacks are not ‘biological’ and that a phobic attitude is required, and/or certain temperamen-tal factors. Others attempt an integrated model utilizing both ﬁ ndings of biological differences and psychological factors of 
temperament and child-rearing practices.

There is limited evidence with appropriate population-based samples to clearly delineate the course of panic disorder. Available evidence suggests that panic disorder is a stable but chronic condi-tion once criteria for the disorder are met. Most patients seeking treatment have experienced chronic, frequently chronically wors-ening, illness generally for 10 to 15 years prior to diagnosis.
(7)
However, other evidence does suggest that there is heterogeneity in terms of course.
As previously mentioned, the Klein model suggests that sponta-
neous panic attacks are the first manifestation of the illness, followed by anticipatory anxiety, and agoraphobia in some indi-viduals. However, for most panic disorder patients examined closely, a panic attack is rarely the ﬁ  rst symptom. In some studies, over 
90 per cent of patients have had mild phobic or hypochondriacal, milder symptoms prior to the onset of their ﬁ  rst panic attack.

The ﬁ  rst panic attack is usually in a ‘phobogenic’ situation such 
as a public place, street, store, public transportation, crowd, eleva-tor, tunnel, bridge, or open space. As mentioned, these are often preceded by stressful life events.
The earliest studies indicated low-recovery rates with chronic 
waxing and waning in most patients. Some individuals have outbreaks of symptomatology with less difﬁ  culty in between, but 
the majority of untreated individuals seem to have a more or less continuous symptom picture which ranges from mild to severe.
Recovery rates vary from 25 to 75 per cent for 1 to 2 years 
follow-up. Over a 5-year follow-up, only 10 to 12 per cent had fully recovered in one study and 30 per cent in another. The most com-mon picture is about 50 per cent of patients are neither well nor very sick with mild symptoms most of the time.

(40) After diagnosis 
and some sort of treatment, functional recovery occurs in the majority of patients.
(41)
In acute pharmacological trials, 50 to 70 per cent of patients have 
excellent acute responses with another 20 per cent having a moder-ate response. With behavioural therapy, again the majority of patients recover and in some trials over 75 per cent of patients are much improved 1 to 9 years following therapy, with an average decrease in symptoms of 50 per cent.
(42)
Poor responses were most consistently associated with initial 
high symptom severity and high agoraphobic avoidance at baseline. Poor response is also associated with low socio-economic status, less education, longer duration, limited social networks, 
death of a parent, divorce or unmarried status, and personality disorders.
Treatment

Treatment
Multiple effective treatments have been developed since the early 1960s and include both psychological and pharmacological treat-ments. Both exposure-based treatments and imipramine were shown to be effective in treating panic disorder and agoraphobia in the early 1960s.
(3,4,43) Psychological-based treatments have moved 
increasingly towards cognitive behavioural therapy with efﬁ  cacy 
roughly comparable to pharmacological treatments.
Imipramine and monoamine oxidase inhibitors (MAOIs) were 
the ﬁ  rst medications shown to effectively treat panic disorder in the 
1960s.(3,44) The high-potency benzodiazepines (alprazolam and 
clonazepam) were also shown to be effective in the 1980s.(7) Most 
now agree that the selective serotonin reuptake inhibitors (SSRIs) are the medication of ﬁ  rst choice.
(45–47)
Factors that inﬂ  uence the choice of initial treatment include

(45–47)
Factors that inﬂ  uence the choice of initial treatment include 
patient preference and past history of treatment response, costs, and often availability. Medication treatment is usually easier to obtain but does involve significant costs and side effects. Although many patients prefer psychological treatments, as many as 10–30 per cent refuse treatments that involve exposure to fright-ening situations or resist the time and effort required. Where avail-able, CBT can be more cost-effective than medications.
CBT has been modiﬁ  ed in various ways to try to make it more 
easily available. This has included delivery in groups by computer or telephone or in shorter amounts or in a high intensity strategy with multiple hours of therapy over just a few days. All of these approaches show promise. There is clear evidence that bibliotherapy

with and without phone contacts is also effective.
Eye movement desensitization and reprocessing (EMDR) was 
developed for treatment of post-traumatic stress disorder. The evidence available suggests that it is not effective in panic disorder.
Panic disorder can have an onset prior to adolescence, and it does 
occur frequently during adolescence. Although empirical data are very limited, it is generally assumed that treatments effective in adults are also effective in children. (see American Academy of Child and Adolescent Psychiatry’s Practice Parameters for the 
Assessment and Treatment of Children and Adolescents with Anxiety Disorders .
(48)
Medication treatments
(a) Selection of initial pharmacotherapy
Evidence indicates that medication from ﬁ  ve classes—the SSRIs, 
SNRIs, benzodiazepines, tricyclics (TCAs), and monoamine oxidase inhibitors (MAOIs) are all roughly equal in their efﬁ  cacy

SNRIs, benzodiazepines, tricyclics (TCAs), and monoamine oxidase inhibitors (MAOIs) are all roughly equal in their efﬁ  cacy 
and therefore the choice of initial therapy should be made on other factors such as tolerability, cost, prior treatments, etc. (see Table 4.7.3.2). For patients with a history or concurrent depression (usually 25 per cent), the antidepressants would be preferable to the benzodiazepines. The antidepressants generally take 4 to 6 weeks to become effective, whereas the benzodiazepines begin working within the ﬁ  rst week. There is evidence that adding benzo-
diazepines to the antidepressants speeds the therapeutic response. 4.7.3 panic disorder and agoraphobia

SECTION 4  clinical syndromes of adult psychiatry 756
A hyperstimulation reaction has been observed to all of the anti-
depressants and has lead to the widespread use of very low doses initially with gradual escalation. Benzodiazepines do not appear to produce the initial hyperstimulation response and are therefore preferred by many patients. However, difﬁ  culties with tapering 
and discontinuing benzodiazepines are the principal negative consideration for their use.
(b) Selective serotonin reuptake inhibitors (SSRIs)
In the United States, there are now six SSRIs available and three have FDA approval for panic disorder (ﬂ  uoxetine, sertraline, and 
paroxetine—IR and CR formulations). There is no scientiﬁ  c or 
even clinical evidence to suggest signiﬁ  cant differences in efﬁ  cacy

even clinical evidence to suggest signiﬁ  cant differences in efﬁ  cacy 
between the SSRIs in this indication. However, there are differences in side effects, principally, weight gain and discontinuation symp-toms, different potential drug interactions, and availability of generic formulations.
(49)
Initial jitteriness or increased anxiety are observed with the 
SSRIs. Therefore, treatment is often begun with the lowest doses available (see Table 4.7.3.3). Some patients do respond at lower doses, although most require higher doses (again see Table 4.7.3.3). The reason the SSRIs are generally regarded as the ﬁ  rst choice for 
pharmacotherapy include their better tolerability and absence of anticholinnergic effects, compared to the TCAs. Patients often have mild difﬁ  culties with nausea, insomnia, headache. Certainly, the

most problematic side effect is sexual dysfunction in both men and women, most frequently delay in orgasm. There are rare reports 
of extrapyramidal side effects and gastrointestinal bleeding. Discontinued too rapidly, withdrawal symptoms of headache, irritability, dizziness, can appear in the ﬁ  rst 1 to 5 days after 
withdrawal, and generally clear within 1 to 2 weeks. These can generally be avoided by taper over 1 to 3 weeks.
(c) SNRIs
The SNRI venlafaxine has recently been demonstrated in large multicenter trials to be effective in the range of 75 to 225 mg/day. The side effect proﬁ  le was similar in severity and symptomatology 
to the SSRIs, although a small number may develop sustained hypertension. There is some evidence that venlafaxine can result in higher rates of death from overdose than the SSRIs.
(d) Tricyclics (TCAs)
The ﬁ  rst trial demonstrating that imipramine was signiﬁ  cantly 
better than placebo was published in 1964(3) and was followed by

better than placebo was published in 1964(3) and was followed by 
multiple controlled trials demonstrating its effectiveness. There is also a significant number demonstrating effectiveness of clomipramine and some even demonstrating greater efﬁ  cacy than 
imipramine.
(50,51) Some data are supportive of desipramine and 
nortriptyline. Consistent problems with poorer tolerability compared to the SSRIs has lead to the TCAs being used only infrequently.
(e) Benzodiazepines (BZs)
The most widely studied and utilized benzodiazepine has been alprazolam. The largest trial was the Cross National Collaborative Table 4.7.3.2  Advantages and disadvantages of various antipanic 
agents
Advantages Disadvantages
SSRIs Well-tolerated antidepressant Initial activation
Safe in overdose
Little weight gain
Once-daily dosingNausea, headache, asthenia, 
 insomnia initially
Sexual side effects

SNRIs Very similar to SSRIs Hypertension
Benzodiazepines Rapid efﬁ  cacy Sedation
Reduce anticipatory anxiety Some memory problemsWell tolerated WithdrawalNo initial activation Abuse potentialSafe in overdose Rare sexual dysfunction
Tricyclic 
antidepressantsSingle daily dose
Less expensive
Long experienceAntidepressantInitial activation
Anticholinergic side
 effects
Weight gainOrthostatic hypotension
Dangerous in overdose
Sexual dysfunction
MAOIs More effective (against 
comorbid depression)?Dietary restrictions
Hypertensive crises (rare)
Initial activation, insomnia
Onset delayedAnticholinergic side effectsOrthostatic hypotensionDangerous in overdoseAntidepressant
Table 4.7.3.3  Medication doses in treatment of panic disorder
Starting dose mg/day Therapeutic range mg/day
SSRIs
 Paroxetine 10–12.5 CR 10–40*

SSRIs
 Fluoxetine 2.5–10 10–20
 Sertraline 25 50–200** Fluovoxamine 50 100–300 Citalopram 10 20–30*** Escitalopram 5 5–10
SNRIs
 Venlafaxine 37.5 75–225
TCAs
 Imipramine 10 50–200 Clomipramine 25 25–150
BZs TID or QID Acute total daily dose
 Alprazolam 0.25–0.5 2–10
†
 Clonazepam 0.25–0.5 1–4
 Lorazepam 0.5 1–7 Diazepam 5 5–40
MAOIs BID
 Phenelzine 15 15–45 (or 90)
 Tranylcypromine 10 10–40 (or 70)
*40 mg demonstrated as target dose in RCT.
**All doses equivalent in one trial 50, 100, 200.
***In one trial, 20–30 was more effective than 40–60 mg/day.
†Mean dose 5.4 mg/day in largest trial.

757
Panic study involving more than 1000 patients and 11 trials, the 
majority of which were double-blind.(7) Alprazolam was effective 
against all of the symptoms of panic disorder, was comparable to imipramine and better tolerated. A sustained release form of alprazolam which can be taken once-daily is currently available. This formulation’s long half-life appears to have solved the inter-
dose rebound symptoms and ‘clock watching’ which was problem-atic with the immediate release form.
Clonazepam has also been demonstrated to be effective and is 
FDA approved for panic disorder in the United States.
(52) Diazepam

(52) Diazepam 
and lorazepam have also been shown to be clinically effective. Although generally well tolerated, the benzodiazepines principal side effects include sedation, occasional ataxia, slurred speech, and small increases in memory complaints. The largest concern and controversy has been with the possibility of dependency and the possibility of recreational abuse. However, the American Psychiatric 
Association Task Force on Benzodiazepine Dependence, Toxicity and Abuse , based on multiple large trials stated ‘there are no data to sug-
gest that long-term therapeutic use of benzodiazepines by patients commonly leads to dose escalation or to recreational use’ .
(53) Doses 
in long-term treatment are either similar to short-term or lower. Discontinuation symptomatology is perhaps the largest problem with the benzodiazepines. Panic patients have more difﬁ  culty dis-

continuing benzodiazepines than patients with generalized anxiety disorder. Symptoms are often seen during taper and are greatest during the last part of taper and the ﬁ  rst week after taper. It is 
inconclusive whether these symptoms represent withdrawal, rebound or relapse, or the combination. However, it is clear that abrupt discontinuation results in greater symptomatology than a gradual taper. Most experts suggest a taper over several months (2–4 months).
(54) Gradual taper and personality issues (more 
symptoms with a higher anxiety sensitivity and avoidance) are more critical than half-life of the medication.
Daily doses of alprazolam have varied from 2 to 10 mg. Greater 
efﬁ cacy is generally seen with higher doses, and the largest trial 
averaged 5.4 mg/day
(7) (see Table 4.7.3.3).

Doses of clonazepam are often 50 per cent or less than doses with 
alprazolam.(52) Some clinicians prefer clonazepam over alprazolam 
because its longer half-life allows it to be used less frequently each day.
(52) However the recent availability of an extended release once 
daily alprazolam (alprazolam ER) has perhaps reversed that issue. Although the BZs are generally safe in overdose, there is recent evi-
dence that alprazolam is associated with more morbidity than the

dence that alprazolam is associated with more morbidity than the 
other BZs. There are studies demonstrating that lorazepam is effec-tive averaging 7 mg/day and 5 to 40 mg/day is effective in diazepam trials (Table 4.7.3.3). The most important aspects of benzodiaze-pine treatments are the rapid response and increased tolerability and perhaps the greater reduction in everyday anticipatory anxiety (Table 4.7.3.2). Certainly, the largest drawbacks are in general the lack of efﬁ  cacy against depression and difﬁ  culties with the tapering 
and discontinuation of treatment.
(f) Monoamine oxidase inhibitors (MAOIs)
Many experienced clinicians feel the MAO inhibitors may be the most effective medication class in treatment of panic disorder. However, there is only one scientiﬁ  cally rigorous trial supporting 
its use.
(44) Further, concerns about its safety and the requirement

its use.
(44) Further, concerns about its safety and the requirement 
of a tyramine diet limit their use. Modern studies aimed at developing reversible inhibitors of the MAOI enzyme that could eliminate the dietary restrictions have unfortunately been disap-
pointing. The MAOI-B inhibitor selegiline has recently been made available in the United States but there are no known studies of its use in panic disorder.
Patients must also avoid sympathomimetic agents frequently 
found in decongestants, the antibiotic linezolid, meperidine, fen-tanyl, and tramadol, serotonergic agents like fenﬂ  uramine and the 
migraine triptan medications. Other signiﬁ  cant side effects include 
weight gain, sexual dysfunctions, postual hypotension, anticholin-ergic side effects, and sleepiness.
(g) Other antidepressants

There are two uncontrolled trials of buproprion and buproprion SR in panic disorder, one positive and one negative. Mirtazepine has limited evidence supporting its use, as does inositol. Reboxetine has positive and negative evidence, as does with buspirone.
Although there is no evidence that conventional antipsychotic medications are effective, there is growing clinical use of the atypical antipsychotics, particularly in treatment resistant patients. There are single trials suggesting the anticonvulsants valproate and levetiracetam may be effective.
(i) Antihypertensives
Although widely used by non-psychiatric physicians in panic patients, the evidence suggests that propranolol, although it does reduce heart rate, is ineffective in treating panic disorder.

(j) Second-line medication treatments
There is limited scientiﬁ  c evidence to guide the clinician in the 
choice of the second course of treatment if the ﬁ  rst is ineffective. 
Clinically, if the patient has experienced some beneﬁ  t from the ﬁ  rst 
medication, most clinicians would either add a benzodiazepine or CBT (which has been shown to work in SSRI failures). If the ﬁ  rst 
treatment is completely ineffective, certainly switching treatment to a different SSRI or a different class of medications would be reasonable. If the second-line treatment is also ineffective, there is preliminary evidence that use of the atypical antipsychotics, olanzapine, or resperidone might be appropriate in severe non-responsive patients, and the other atypicals are also likely to work.
(k) Length of treatment

If patients do respond to an antidepressant, continuing treatment for 6 months or longer generally results in continued improvement and a decreased risk for relapse and recurrence, especially if symptoms remit.
(55) Response is generally retained as long as 
medications are maintained. Most studies, clinical experience, and consensus opinion suggests continuation of effective medications for 12 to 18 months or longer.
(l) Discontinuing treatment after an effective response
Although antidepressants can be tapered over 10 days, clinical evi-dence recommends a much slower taper involving weeks to months. With benzodiazepines, it appears critical to taper even more slowly. Discontinuation symptoms are common but are signiﬁ  cantly min-
imized if taper is accomplished over 2 to 4 months.
(56) CBT has 
been demonstrated to be helpful in decreasing discontinuation dif-ﬁ culties when focused on the sensations, bodily symptoms, and

been demonstrated to be helpful in decreasing discontinuation dif-ﬁ culties when focused on the sensations, bodily symptoms, and 
catastrophic misinterpretations that are often seen.4.7.3 panic disorder and agoraphobia

SECTION 4  clinical syndromes of adult psychiatry 758
(a) Psychodynamic psychotherapy
Although psychodynamic psychotherapy remains a popular 
treatment for all psychiatric disorders including panic disorder, there has been very little research demonstrating its efﬁ  cacy in 
panic disorder. There is one large case-report study of patients with panic disorder reporting that most patients did respond well. One trial compared clomipramine with clomipramine plus 15 weekly sessions of brief dynamic psychotherapy. Patients in both groups responded well with 75 per cent of the patients in the clomipramine group being panic free and all of the patients in the combination group.
In an extension of this work, an emotion-focused treatment for

In an extension of this work, an emotion-focused treatment for 
panic disorder has been developed which explores typical fears of being abandoned or trapped as stimuli for panic attacks. This often involves a 12-session acute treatment with six sessions of monthly maintenance in which patients are encouraged to identify, reﬂ  ect 
upon, and attempt to change problematic feelings and their responses. A specific form of dynamic psychotherapy ‘panic-focused psychodynamic psychotherapy’ which is generally applied in 3-month increments, was recently shown to be effective in a RCT.
(57)†
Behavioural treatments
(a) Exposure treatments
Behavioural treatments which utilize in vivo  exposure to phobic

(57)†
Behavioural treatments which utilize in vivo  exposure to phobic 
situations have been the mainstay of the behavioural treatments of panic disorder. They are based on the theory and evidence that patients who enter a feared situation experience habituation of their anxiety whether they are exposed slowly or suddenly and extensively (ﬂ  ooding). The critical nature of exposure for improve-
ment was made clear in one study in which patients being treated with imipramine received no improvement from imipramine when given anti-exposure instruments.
(58) However, they signiﬁ  -
cantly improved if it were simply suggested that they re-expose themselves to their previously phobic situations when ready. Exposure treatment is consistently associated with long-lasting continuation of acute improvements even without formal follow-up treatment.
(59)
Studies have compared use of exposure therapy to cognitive

(59)
Studies have compared use of exposure therapy to cognitive 
behavioural therapy, and have found them to be essentially equal in efﬁ cacy.
(60) At this point, exposure has become an integral part of 
most CBT protocols.
(b) Cognitive behavioural therapy (see Chapter 6.3.2.1)
Cognitive behavioural therapy of panic disorder evolved from early work of Aaron Beck, but has been applied to panic disorder pri-marily by Barlow and colleagues working in the United States
(42,61)
and by Clark in the United Kingdom (see Chapter 6.3.2.1).
CBT for panic disorder usually begins with education (e.g. symp-

(42,61)
toms are part of body’s fear response and aren’t dangerous) about panic and the cognitive model of panic attacks, use of diaries for self-monitoring of symptoms, cognitive restructuring, habituation to fearful cues including internal cues (e.g. dizziness, tachycardia, etc.) and external situations (e.g. public places, elevators, etc.), anxiety management techniques (e.g. diaphragmatic breathing), and education to prevent relapse. Although evidence suggests that breathing retraining is not an essential component of effective 
CBT, it is widely utilized as an anxiety management technique.
The most informative trial to date was a multicentre (N 312) 
11-week acute trial with a 6-month follow-up for responders and a 
6-month follow-up after discontinuation of treatment.
(62) This

(62) This 
trial compared imipramine to cognitive behavioural therapy, their combination, and placebo. Improvement in all the active treatment cells was approximately equal at the end of the acute trial and sig-niﬁ cantly greater than placebo on most measures. This was also 
true at the 6-month follow-up. Interestingly, responders to imipra-mine had a more robust response than responders to cognitive behavioural therapy alone. The combination of imipramine plus cognitive behavioural therapy was signiﬁ  cantly better than CBT or

imipramine treatment alone at the 6-month point where all treat-ments were still present. However, at follow-up 6 months after treatment, none of the treatment cells were statistically different from placebo. There are many well-controlled trials demonstrating that CBT delivered in various forms and formats is effective. Its effects are robust, and at least comparable to medications.
(62–64)
Beneﬁ  ts are generally long-lasting, with or without booster sessions 
in follow-ups to 5 years.(63,65) CBT delivered in a group format is 
also effective.
Continuation/maintenance treatments

There are now a series of studies utilizing antidepressants or ben-zodiazepines as maintenance treatment for 6 and 12 months for panic disorder and agoraphobia. In most trials, treatment gains from acute treatment are almost always maintained, and generally are extended while the medication is continued. In a 12-month trial comparing clomipramine and placebo, the clomipramine group continued to improve and tolerated the medication well. Placebo patients who were switched to active medication matched the good responses of the clomipramine group.
In a 6-month continuation study of alprazolam patients follow-
ing an 8-week initial trial, the group maintained their efﬁ  cacy with

ing an 8-week initial trial, the group maintained their efﬁ  cacy with 
a dose at the end of the 8-week trial of 5.1 ± 2.3 mg/day. This decreased to 4.7 ± 2.1 mg/day at week 32 and subsequent follow-up 1 to 2 years later found most patients’ doses had drifted down to 
1 to 2 mg/day.
In the large follow-up to the Phase II Cross-National Panic Trial, 
there was a 32-week double-blind comparison of alprazolam, imip-ramine, and placebo in 181 patients. Again, efﬁ  cacy was maintained 
with both medications with no escalation of dose. Patients on both active treatments generally extended their improvement, although the placebo patients tended to lose some efﬁ  cacy and certainly had

a higher drop-out rate. A long-term extension continued parox-etine, clomipramine, and placebo in 176 patients following an acute trial. During the 1-year extension, both the paroxetine and clomipramine patients continued to improve and again, placebo patients tended to lose some of their initial response.
As evidence has accumulated of the high relapse rate with dis-
continuation of effective medication treatments for panic disorder, longer-term treatment, generally 6 to 18 months, has become rou-tine. Although not well documented, perhaps one of the more important issues is that it appears that patients not only continue to improve for the ﬁ  rst 6 months but that improvements continue 
to be extended the longer patients are on treatment, perhaps even throughout the ﬁ  rst 2 years of treatment.

759
Available evidence remains inconclusive about the percentage of 
patients who will relapse if effective pharmacotherapy of panic dis-order is discontinued. Early estimates suggested that most patients relapse. It remained the prevailing opinion that 35 to 85 per cent of patients relapse after antidepressants or benzodiazepines were discontinued. However, one trial reported almost no relapse after discontinuation of clomipramine patients, perhaps because they used a gradual taper.
The early trial by Zitrin et al. reported only 26 per cent relapse.
(65)
In a modern trial comparing imipramine and cognitive behavioural 
therapy, the imipramine relapse rate was 40 per cent. One of the most carefully performed relapse prevention trials followed a ﬁ  xed-

dose study of paroxetine. After acute treatment, patients were re-randomized in double-blind fashion to receive either paroxetine at their prior dose, or to placebo for an additional 3 months of treatment. Interestingly, only 30 per cent of the patients randomized to placebo relapsed, compared with 5 per cent relapse if paroxetine was continued.
(47) The relapse rate after medication 
discontinuation in a recent trial was only 14 per cent. Although these studies certainly need replication, it suggests that the relapse rate may be lower than previously estimated if patients are slowly tapered and carefully followed.
There is one small study that suggests that the relapse rate is

There is one small study that suggests that the relapse rate is 
lower if treatment is longer. Mavissikalian followed a small group of patients who responded to imipramine, discontinuing some after 6 months of treatment and the other group after 18 months of treatment.
(66) In these patients, there was an 80 per cent relapse 
rate in the 6-month treatment group, but only 20 per cent in the 18-month treatment group. This suggestive ﬁ  nding is consistent 
with clinical experience but certainly needs replication; however, it is certainly supportive of the general recommendation of continued treatment for 12 to 18 months if effective.
There is certainly a strong suggestion that rapid taper of benzo-
diazepines produces signiﬁ  cant withdrawal symptoms which prob-
ably stimulates relapse.

The suggestions for management in this section are based on evidence of the empirically based treatments in panic disorder and agoraphobia, much of which has been reviewed above. However, as in treatment of all patients, there are suggestions that also involve the ‘art’ of treating these patients which have evolved, but have not been empirically studied or conﬁ  rmed.
Management of the uncomplicated patient
As reviewed above, it appears clear that the average patient with 
panic disorder can be treated with a variety of medications or exposure-based and/or cognitive behavioural treatments designed for panic disorder with approximately equal efﬁ  cacy. There are

panic disorder can be treated with a variety of medications or exposure-based and/or cognitive behavioural treatments designed for panic disorder with approximately equal efﬁ  cacy. There are 
some patients who have strong feelings or prejudices for or against both medication and cognitive behavioural treatments. Given that situation, as well as the lack of any clear reason to choose one treat-ment over the other, ethical practice would dictate offering patients a choice of treatment. There is also some evidence that patients will respond better to the treatment they ‘believe in’ . Unfortunately, the types of treatments are not equally available in all settings or all countries. Psychiatrists tend to use medication treatment with education, exposure, and cognitive based work of a less systematic

nature than psychologists and other non-physician caregivers. Although many behaviourally and cognitively oriented psycholo-gists do afﬁ  liate with psychiatrists and other physicians to provide 
medications, for many this ease of combination treatment is not readily available.
As mentioned, most psychiatrists utilize one of the medications 
mentioned above, supplemented by clear educational efforts with the patient and pertinent family members. This generally includes use of some written material which the patient and spouse read and discuss with the psychiatrist. (see Appendix for suggestions) Education is also a critical part of the initial treatment of patients in exposure-based treatments and cognitive behavioural therapy. These educational efforts are almost always very helpful and in the more mildly symptomatic patients may sufﬁ  ce. Certainly a central

issue to increase the therapeutic alliance is to make clear that the therapist does understand that panic attacks involve marked ‘real’ physical symptoms which are extremely frightening, even though they are not dangerous and are short-lived generally.
For the patient who will be prescribed medication, it is most rea-
sonable to offer a discussion of which medications might be appro-priate, and the pros and cons of each. As outlined in Table 4.7.3.2, each medication is different, and depending upon the individual patient’s needs and previous experience, any of the classes of medi-cations might be appropriate. As mentioned, current opinion would suggest that the medication of ﬁ  rst choice, would probably 
be an SSRI. In a recent meta-analysis of all the effective medica-tions utilized in the treatment of panic disorder, the SSRIs were shown to be more effective than the other classes.
(67) Coupled with

(67) Coupled with 
their greater tolerability, lack of weight gain, and safety in overdose, they would appear to be the logical ﬁ  rst choice.
For clinical and other practical issues, all patients should be told 
initially that whatever medication is the initial treatment, there are multiple other effective medications. It is important to emphasize that there is little way of knowing which speciﬁ  c medication is most 
appropriate for which patient and that the initial choice may not be effective, but subsequent choices are likely to be effective.
There are few data to direct the choice of the medications beyond 
those favouring the SSRIs mentioned above (see Table 4.7.3.2). There is only one trial documenting a difference in patient type leading to a choice of medication. In the large cross-national comparison of imipramine, alprazolam, and placebo, patients 
with predominantly respiratory symptoms responded better to 
(68) Similarly, patients with a predominantly cardio-

vascular symptom picture responded better to alprazolam than imipramine. Otherwise, there are no data suggesting a particular medication for a speciﬁ  c patient beyond the various advantages 
and disadvantages listed in Table 4.7.3.2.
Once medication is chosen, it is prudent to begin at the lowest 
dose possible (see Table 4.7.3.3). This beginning low dose also extends to the benzodiazepines but is less critical since they are not associated with an initial hyperstimulation reaction. This is one of the reasons why benzodiazepines are easier to utilize and usually more popular with patients who somehow realize that from previ-ous experience or feedback from other patients that they are not associated with an initial worsening of symptoms and are better tolerated overall. At a practical level, management of the worries

about the initial hyperstimulation reaction is one of the most 
important issues in the psychopharmacological management of 4.7.3 panic disorder and agoraphobia

SECTION 4  clinical syndromes of adult psychiatry 760
panic disorder patients. If handled incorrectly, this issue can lead to 
a drop-out rate that reaches 25 to 50 per cent. With proper reassur-ance and close follow-up of patients, this drop-out rate can be reduced to almost zero. Patients need to be told that hyperstimulation can occur in one-third of patients but is transient and not danger ous. 
Because of the inherent anxiety and even phobia about taking medications, this reassurance is not usually sufﬁ  cient and patients 
need to be invited to contact the treating physician with any anxiety or questions they might have about taking medications coupled with a quick response to their concerns.
After initial tolerance of medication is established, the dose can 
be raised over several weeks to a target level. Obviously, if a patient does not show a response at lower doses, the medication should be raised to maximum doses (Table 4.7.3.3).

It is important for the patient and physician alike to keep in mind 
that effectiveness of medications often requires a significant amount of time. The antidepressants as a class routinely take 2 to 6 weeks and with certain medications and patients as much as 6 to 12 weeks before signiﬁ  cant effectiveness is established. This is less 
an issue with benzodiazepines, where initial effectiveness is gener-ally seen in the ﬁ  rst week or two, but there too the appropriate 
doses must be obtained, which often takes several weeks. Higher 
doses of all medicines are needed to reduce agoraphobic 
avoidance.
As mentioned, if agoraphobic patients do not gradually

As mentioned, if agoraphobic patients do not gradually 
re-expose themselves to situations they fear, their avoidance fears will not be decreased. This exposure to their actual phobic situa-tions can be accomplished in many ways. Some patients are capable of gradually re-exposing themselves after they understand the principles of exposure and the need to remain in the situation until their fears diminish. They may need help in establishing a hierar-chy of their fears, although it is not actually necessary that they in fact do work-up the hierarchy in a gradually increasing fashion from ‘least feared’ to ‘most feared’ . However, it is often easier for most patients to conceptualize and accomplish it in this fashion.
Many therapists develop a hierarchical list and then monitor the

Many therapists develop a hierarchical list and then monitor the 
patient’s progress on a regular basis. Use of a standard scale which monitors the various symptom domains can be very helpful, such asThe Panic Disorder Severity scale  (PDSS).
(69) There is evidence 
that the exposure must be regular, and extensive, often on a daily basis. Also, encouragement from the therapist and partner have both been shown to be important. Some patients can re-enter their phobic situations better if supported by their partner, or other phobics from a support group. If they are particularly afraid, an in vivo  therapist (often recovered phobics) can be very helpful. The 
critical issues appear to be approaching their fears in a consistent and systematic basis in the real phobic situations accompanied by encouragement and support.
In a similar fashion, many psychiatrists combine principles of

In a similar fashion, many psychiatrists combine principles of 
cognitive behavioural therapy without embarking on a formal cognitive behavioural therapy programme. Certainly, this should always involve education about the illness and its treatments. Other 
elements of identiﬁ  cation and challenge of catastrophic thinking 
are widely applied by psychiatrists, but in a less systematic fashion than in formal cognitive behavioural therapy protocols.
It is important that from the beginning most patients be told 
that if medication treatment is effective, the expectation is tocontinue the medication for 12 to 18 months. An important issue to negotiate with the patient is how, when, and if effectivepharmacotherapy should be tapered and discontinued.
(70) Most 
evidence and experience suggests that patients be continued long enough to receive maximum beneﬁ  t from medication treatment.

(70) Most 
evidence and experience suggests that patients be continued long enough to receive maximum beneﬁ  t from medication treatment. 
In that context, patients should have experienced symptomatic and functional recovery to a maximum extent possible before discon-tinuation is considered. Patients should have regained a sense of conﬁ  dence and control of their symptoms and lives. This might be 
conceptualized as a ‘period of normal living’ after attainment of symptomatic control before consideration is given to discontinu-ing an effective treatment. Relapse rates after such a remission are lower. Because the principal danger of discontinuation is relapse, the time should be carefully chosen. This should be a time when potential disruption from discontinuation symptoms and/or relapse would be least problematic.
There are strong suggestions in the literature, some of which is

There are strong suggestions in the literature, some of which is 
reviewed above, that all medications, and certainly the benzodiaz-epines, should be tapered very slowly, probably over 2 to 6 months, if possible.
(54) This is both to minimize withdrawal symptoms 
which are especially frightening to panic patients and to observe for relapse symptoms as medications are slowly tapered.
The strongest reasons for discontinuing effective pharmacother-
apy are the problematic side effects and expense.
(70) Because this is 
a syndrome frequently seen in young women, the most important reason may be the wish to conceive a child or the onset of preg-nancy. Certainly, routine practice is to try to taper and discontinue all medications before or during pregnancy, but sometimes this is not possible. There are now a series of women who have delivered normal children after having tried unsuccessfully to discontinue medication during pregnancy.

Many patients want to manage their own symptoms without the 
use of medications, and this is also a reasonable reason to taper and discontinue medications, if strongly felt by the patient.
(70) The 
therapist should explore, however, unreasonable prejudices against the use of medications stimulated by reading, television shows, relatives, or even well-meaning physicians. Most in the ﬁ  eld now 
believe that panic disorder and agoraphobia are conditions similar to hypertension and diabetes in the sense that most patients do not like the thought that they are ill and resist compliance with medica-tion treatment. However, treatment is beneﬁ  cial and not harmful, 
and patients often need encouragement and education in order to agree to a programme where they continue medications rather than press to discontinue them.
If medications are discontinued, the patient should be followed 
closely, at least by telephone, for difﬁ  culties that could include

closely, at least by telephone, for difﬁ  culties that could include 
withdrawal symptoms, especially with benzodiazepines, or incipi-
ent relapse. If relapse does occur, evidence suggests that patients 
will respond to reinstitution of the same medication treatment regimen. If symptoms and/or functional disability associated with relapse are problematic, patients should be offered retreatment with the same medication or offered other effective non-medication treatments.
Management of patients with predominantly psychological treat-ments also begins with the use of educational materials, as is frequently the case with medication treatment of panic disorder. Almost all psychological treatments involve some sort of exposure-based treatment. In some, this is the predominant modality with considerable variation on how exposure to feared situations is

761
accomplished. Although some initial exposure therapy in particu-
larly frightened patients may be accomplished in imagination prior to in vivo  exposure, most exposure treatments are usually 
attempted in vivo  from the outset. Most treatments have been 
shown to be effective if they involve in vivo  exposure. Gradual 
exposure is the norm, although some programmes use very rapid exposures often called ‘ﬂ  ooding’ , which involves exposure to mul-
tiple phobic situations rapidly over several days. Most programmes involve therapist-assisted exposure, sometimes utilizing profes-sional in vivo  therapists or volunteers who accompany phobics into 
their feared situations. Partners of patients are often enlisted as assistants, and there is some evidence that this more effective than non-partner exposure aides.
Most exposure-based treatments involve frequent, often daily

Most exposure-based treatments involve frequent, often daily 
practices involving several hours. Often the critical issue is adequate support of the patient to accomplish this much exposure ‘home-work’ , as well as encouragement and praise.
Almost anything that can help the patient accomplish the 
actual exposure appears to be useful and helpful. For instance, manuals and computer programs, as well as telephone-based supervision and encouragement have been shown to be effective. Although many therapists utilize relaxation techniques, applied 
relaxation has been the most widely utilized and effective. Many

relaxation has been the most widely utilized and effective. Many 
therapists also employ breathing retraining, encouraging people who hyperventilate to slow their breathing by utilizing theirdiaphragm. Although both have been shown to be effectiveand are widely utilized, other studies suggest they are notessential components of treatment, and their use does vary. Although use of benzodiazepines do decrease patient anxiety about exposure, evidence suggests that the benzodiazepines interfere with the cognitive beneﬁ  ts and habituation effectsof exposure.
Cognitive restructuring involves the patient and therapist identi-

fying the so-called ‘automatic thoughts’ they have with and after each panic attack. These are the misinterpretations that patients make about what these symptoms mean. For instance, the patient and therapist together identify that these symptoms often trigger thoughts that they are very ill, having a heart attack, or perhaps even dying. Over several sessions, these are identiﬁ  ed and it is made

clear to the patient the power these thoughts have to frighten them. At that point a number of strategies can be tried to try to correct these cognitions. Some involve attempts to compute the actual probability of the catastrophic consequences that patients fear. Others involve ‘decatastrophizing’ in which the ultimate conse-quences that patients fear are exposed, and generally can then be disavowed by the patient as extremely unrealistic. Patients can be taught to correct these thoughts or substitute more positive self-statements in their place. These skills are then worked on as ‘home-work’ , including actual exposure in which negative thoughts are 
identiﬁ  ed and challenged in vivo .
The other usual aspect of cognitive behavioural therapy for 
panic disorder is interoceptive exposure, in which physical symp-toms that frighten patients are identiﬁ  ed and then they are taught

panic disorder is interoceptive exposure, in which physical symp-toms that frighten patients are identiﬁ  ed and then they are taught 
to habituate to those symptoms and challenge the negative cogni-tions that arise with them. This can easily be accomplished in an ofﬁ ce setting. For instance, if the patients are afraid of dizzy feel-
ings, they can be spun in a chair. If they have fears of fast heartbeat, they can run up the stairs and challenge the negative cognitions that arise.Both exposure-based treatments and cognitive behavioural 
therapy often are delivered in an 8- to 16-week treatment format, with varying frequencies of follow-up and attempts are underway to shorten these treatments. There is evidence that patients failing to respond to CBT often respond to subsequent medication treatment.
Treatment of comorbid patients

Treatment of the panic disorder patient comorbid with substance abuse is probably the most difﬁ  cult challenge. In general, the 
substance abuse problem tends to be predominant even if it were temporally secondary to panic disorder symptoms. Therefore, treatment of substance abuse generally has to be initiated and completed ﬁ  rst, although as soon as possible treatment of panic 
disorder needs be initiated.
Treatment of comorbid social phobia, obsessive–compulsive 
disorder, or GAD has recently been made somewhat simpler with the demonstration that the SSRIs are effective in these other condi-tions as well. Although not yet empirically demonstrated, it is reasonable to expect that an SSRI would effectively treat the panic disorder as well as the other comorbid anxiety disorders. This is an important area for future research. Behavioural treatments speciﬁ  c 
to obsessive–compulsive disorder and to social phobia may well be

to obsessive–compulsive disorder and to social phobia may well be 
needed in addition to medication treatment.
The most common comorbidity is with depression and again 
one of the advantages of antidepressants is probable dual treatment of panic disorder and depression.
(71) Perhaps the most important 
management issue is recognition that comorbid depression carries with it a marked increase in suicide risk. As mentioned, there is some evidence that depressed panic disorder patients respond better to MAOIs.
Resistance to treatment
There are relatively few systematic data about treatment options for patients resistant to initial medication or to exposure- or cognitive behavioural-based treatments. Generally, however, most patients can be tried on another medication, often with success. If they are on medicine and have not tried exposure or cognitive behavioural therapy that should deﬁ  nitely be added. The converse

is also true. Non-response can often be traced to inadequate doses or blood levels of the medication or an inadequate length of trial. Comorbid psychiatric and particularly comorbid medical condi-tions need to be ruled out. Apparent resistance is often related to concomitant personality disorders or failure of agoraphobics to actually attempt exposure treatments. True resistance to one medi-cation is sometimes overcome by a switch to another medication or to two medications at a time. If the combination of an antidepres-sant and benzodiazepine has not been tried, that is often the ﬁ  rst 
attempted combination. In highly resistant patients, sometimes a 
combination of tricyclic and SSRI antidepressants or an atypical antipsychotic can be utilized.
Pregnancy
Panic disorder occurs disproportionately in young women making 
the issue of pregnancy a critical one. The course of panic disorder

Pregnancy
the issue of pregnancy a critical one. The course of panic disorder 
through pregnancy is highly variable. Use of SSRIs may be associ-ated with low birth weight and a higher rate of spontaneous abortions, cardiac abnormalities, pulmonary hypertension, and withdrawal symptoms in the newborn if used late in pregnancy. 4.7.3 panic disorder and agoraphobia

SECTION 4  clinical syndromes of adult psychiatry 762
In general however, increases in congenital abnormalities have 
not been observed with the SSRIs. Whether benzodiazepines are associated with major malformations like cleft palate is unclear. Use of benzodiazepines near delivery is associated with sedation in the newborn. Also, both antidepressants and benzodiazepines are secreted in breast milk. For all these concerns, CBT is strongly recommended for pregnant women and should be considered in women planning pregnancy.
Ethical issues
The principal ethical issues concern the availability of treatment. Because the two types of effective treatments (medications and exposure or cognitive behavioural therapy) are not widely or equal-ly distributed in all practices or locations, sometimes caregivers face a difﬁ  cult ethical choice of having only one type of treatment 
available. In these instances, patients should be informed of the limitations and participate in the choices made.

Most of the treatment experience and certainly the empirical 
evidence has been in Caucasian patients. We do know that symp-toms are different across ethnic groups and that response is often less positive in non-Caucasian groups. Treatments need to be tested and developed for all ethnic and national groups as part of the ethical development of the ﬁ  eld.
The best evidence now suggests that panic disorder is often

preceded by an anxiety pattern in childhood. In Kagan’s modelof behaviourally inhibited children, there is certainly a tendencyfor the pattern to persist throughout life, but some children appear to lose this trait during their development. This may well berelated to parental child-rearing practices in which children are encouraged to face issues they fear rather than be withdrawn and fearful. Research is needed to explore whether different parental rearing practices or educational efforts or early treatment with these children can reduce later development of anxiety disorders.If so, these efforts at the public health and school level need to developed.
The other major preventable aetiological consideration for panic 
disorder and agoraphobia has been the evidence of negative traumatic events occurring in the childhood of adults with panic

disorder and agoraphobia has been the evidence of negative traumatic events occurring in the childhood of adults with panic 
disorder. Preventative efforts need to be aimed at these issues 
through public education and education of caregivers of children. Also, one of the intervention goals in helping a traumatized child should be to prevent future development of anxiety disorders and other problems.
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4.8
Obsessive–compulsive disorder
Joseph Zohar, Leah Fostick, and 
Elizabeth Juven-Wetzler
Obsessive–compulsive disorder (OCD) is a common, chronic, and 
disabling disorder marked by obsessions and/or compulsions that are egodystonic and cause signiﬁ  cant distress to the patients and 
their families. During the last 25 years, there has been a resurgence of studies into various aspects of OCD, including epidemiological, pathophysiological, and pharmacological investigations. With the progress in ﬁ  nding effective treatments for OCD, different algo-
rithms for the management of these patients have been developed. The progress in OCD includes advanced methodologies of imaging studies (both before and after treatment), along with insight into the neurological aspects of OCD and OCD-related conditions, leading to selective treatments.
Up to the early 1980s, OCD was considered a rather rare, treat-

ment-refractory, and chronic condition of psychological origin. Dynamic psychotherapy was of little beneﬁ  t and several pharmaco-
logical treatments were attempted without much success.
(1) Since 
then, several researchers have reported that the prevalence of OCD is around 2 per cent in the general population.
(2,3) In addition, 
numerous studies have reported on the efﬁ  cacy of various sero-
tonin reuptake inhibitors, and consequently an understanding of the biological basis of OCD has begun to unfold.
The observation that clomipramine, a tricyclic antidepressant 
with a serotonergic proﬁ  le, is effective in treating symptoms of 
OCD
(4,5) has increased interest in OCD in general and in the 
relationship between serotonin and OCD in particular. Substantial evidence currently suggests that OCD is almost unique among psychiatric disorders, as only serotonergic medications appear to be effective in this disorder.

(6) For example, non-serotonergic 
drugs, such as desipramine, a potent antidepressant and antipanic agent, are entirely ineffective in OCD.
(7–9) This speciﬁ  c response 
to serotonergic drugs has paved the way for further research on the role of serotonin in the pathogenesis of OCD in particular, and in OCD-related disorders in general.
The lifetime prevalence of OCD in the general population is between 2 and 3 per cent (i.e. it is more prevalent than schizophre-nia).
(2,10)  This rate has been conﬁ  rmed across different cultures.(3)
The prevalence of OCD among children and adolescents appears to be as high as among adults.(11) However, Nelson and Rice(12) and 
Stein et al .(13) have suggested that the diagnosis of OCD by the 
Diagnostic Interview Schedule administered by lay people leads to overdiagnosis, and so have proposed lower prevalence rates of 1 to 2 per cent.
Men and women are equally likely to be affected, although some

Men and women are equally likely to be affected, although some 
reports have suggested a slight female predominance.
(3) During 
adolescence, boys are more commonly affected than girls. The mean age of onset is about 20 years of age. Single people are more commonly affected, probably representing the difﬁ  culty for people 
with OCD to maintain a relationship.
Patients with OCD are commonly afﬂ  icted by other mental 
disorders; for instance, the lifetime prevalence for a major depres-sive episode in these patients is around 67 per cent.
(3,14) Other 
common comorbid psychiatric diagnoses include alcohol-use disorders, social phobia, speciﬁ  c phobia, panic disorder, eating 
disorders, and post-traumatic stress disorder (PTSD).
(15) The

(15) The 
comorbidity with schizophrenia and with tic disorders raises inter-esting pathophysiological and therapeutic implications. The rate of tic disorders approaches 40 per cent in juvenile OCD, and there is an increase in the prevalence of T ourette’s syndrome among the relatives of OCD patients.
(16)
The relationship between OCD and obsessive–compulsive per-
sonality disorder (OCPD) has been a focus of debate. Although prospective research is lacking, it appears that OCPD is not a prominent risk factor for developing OCD, as the prevalence of OCPD among patients with OCD is not far from its prevalence in other psychiatric disorders.

The diagnosis of OCD according to DSM-IV criteria is based on the presence of either obsessions or compulsions, which cause marked distress, are time-consuming (more than an hour per day), or signiﬁ  cantly interfere with the person’s normal routine and 
social and occupational activities. It stipulates that, at some point during the course of the disorder, but not necessarily during the current episode, the person has recognized that the obsessions or compulsions are excessive or unreasonable. However, if the patient does not recognize for most of the time during the current episode that the obsessions and compulsions are excessive or unreasonable, the diagnosis is OCD with poor insight.

SECTION 4  clinical syndromes of adult psychiatry 766
If another Axis I disorder is present, it is mandatory that the 
content of the obsessions or compulsions is not restricted to it (e.g. a preoccupation with food or weight in eating disorders,or guilt feelings in the presence of a major depressive episode). The disturbance should not be due to the direct effects of asubstance (e.g. of a drug abuse or a medication) or a general 
medical condition.
The obsessions are recurrent, intrusive, and distressing thoughts, 
images, or impulses, whereas the compulsions are repetitive,seemingly purposeful, behaviours that a person feels driven toperform. Obsessions are usually unpleasant and increase a person’s anxiety, whereas carrying out compulsions reduces anxiety. Resistance to carrying out a compulsion results in increasedanxiety. The patient usually realizes that the obsessions are irratio-nal and experiences both the obsession and the compulsion asegodystonic.

Patients with both obsessions and compulsions constitute at least 
75 per cent of the affected patients, with most patients presenting with multiple obsessions and compulsions. The symptoms may shift, for example a patient who had washing rituals during child-hood may present with checking rituals as an adult.
OCD can express itself in many different symptoms, but the clas-
sical presentations include washing, checking, aggressive, religious, or sexual obsessions, and ordering, counting, hoarding, and sym-metry compulsions. Dimensional approaches have been used to analyze these characteristic subtypes, and present the different symptoms in an innovative way.
(17)
The most common pattern is an obsession with dirt or germs, 
followed by washing or avoiding presumably contaminated objects (doorknobs, electrical switches, newspapers, people’s hands, tele-phones). Because it is hard to avoid the feared object is (e.g. faeces,

urine, dust, or germs), patients wash their hands excessively and sometimes avoid leaving home because of their fear of germs. 
A second common pattern is an obsession of doubt, followed by a compulsion of checking. The person checks whether the oven is turned off or the front and back doors are closed—the checking may involve many trips back home to recheck what had already been checked. In OCD, the checking, instead of resolving uncer-tainty, often contributes to even greater doubt, which leads to fur-ther checking. The patients exhibit obsessional self-doubt, and feel guilty for having committed some damage (for instance, a fear of hurting someone while driving, leading to driving back over the 
same spot again and again). Other patterns include hoarding and 
religious obsessions. More recently, a dimensional approach to OCD has been launched by Leckman and colleagues, stating four symptom dimension of OCD: obsessions/checking, symmetry/

ordering, contamination/cleaning, and hoarding.
(17,18)  Another 
pattern of OCD involves intrusive obsessional thoughts without a compulsion. Such obsessions are usually repetitious thoughts of some sexual or aggressive act that is reprehensible to the patient. Still another pattern is the need for symmetry or precision, which 
leads to a compulsion of slowness. Patients can take hours to eat 
a meal or shave, in an attempt to do things ‘just right’ . Unlike other patients with OCD, these patients usually do not resist their 
symptoms.
The gap between the knowledge that the symptoms are irrational 
on one hand and the overwhelming urge to perform them on 
the other hand contributes to the immense suffering associated 
with OCD.OCD and schizophrenia

About 25 per cent of patients with chronic schizophrenia may also present with OCD symptoms (range 5 to 45 per cent)
(19); and 
15 per cent of the patients with schizophrenia may fully qualify for the diagnosis of OCD. As in OCD, the OC symptoms in these patients will not necessarily surface unless speciﬁ  c questions are 
asked. Many patients with schizophrenia can distinguish the egodystonic, obsessive–compulsive symptoms, perceived as coming from within, from the egosyntonic delusions perceived as introduced from the outside. Follow-up studies demonstrate a diagnostic stability over the years, and it seems that the presence of OCD in schizophrenia predicts a poor prognosis.
(19) Several

(19) Several 
studies among patients with schizophrenia and OCD reported an improvement in OCD symptomatology after the addition of serotonin reuptake inhibitors.
(19)
The poor prognosis of patients with schizophrenia and OCD, 
preliminary data regarding their response to the unique combina-tion of antipsychotic and anti-obsessive medications, along with the high prevalence of this presentation has led several researchers to suggest that a ‘schizo-obsessive’ category may be of value.
(20)
Personal distress and functional impairment, which are required for the diagnosis, differentiate OCD from ordinary or mildly exces-sive worries, thoughts, and habits. The medical differential diagnosis includes tic disorders (especially T ourette’s syndrome), temporal-lobe epilepsy, trauma, and postencephalitic complications.
Psychiatric diagnoses that should be ruled out include depressive

Psychiatric diagnoses that should be ruled out include depressive 
disorder, schizophrenia, OCPD, PTSD, phobias, delusions, hypo-chondriasis, and paraphilias. OCD can usually be differentiated from schizophrenia by the absence of other schizophrenic symp-toms and by the patients’ insight into their disorder. Moreover, patients with OCD usually attempt to resist the obsessions. OCPD does not have the degree of functional impairment characteristic of OCD and it is egosyntonic.
Phobias are distinguished by the absence of a relationship 
between the obsessive thoughts and the compulsions. The fears in 
OCD usually involve harm to others rather than harm to oneself. In addition, in OCD, when patients are ‘phobic’ they are usually afraid of an unavoidable stimulus (for instance, viruses, germs, or dirt) as opposed to the classic phobic objects like tunnels, bridges, or crowds.
Major depressive disorder (MDD) can sometimes be associated

Major depressive disorder (MDD) can sometimes be associated 
with obsessive ideas, but patients with OCD usually fail to meet all the criteria of MDD. Other psychiatric diagnoses closely related to OCD are hypochondriasis, body dysmorphic disorder, and trichotillomania. As these patients have repetitive worries or behaviours, although they are focal, they are still related to the ‘OCD Spectrum’ .
Many patients with OCD may have an onset of symptoms after a stressful event (e.g. pregnancy, a loss, or a sexual problem). Owing to the secretive nature of the disorder, there is often a delay of 5 to 10 years before patients come to psychiatric attention. However, the delay may shorten due to increased public awareness to the disorder through articles, books, and movies. The course of OCD is

767
usually long, but variable; some patients experience a ﬂ  uctuating 
course, while others experience a chronic course.(21)
About 20 to 30 per cent of the patients show a signiﬁ  cant 
improvement in their symptoms, and 40 to 50 per cent a moderate improvement. The remaining 20 to 40 per cent become chronic or their symptoms worsen.
OCD patients are prone to depression and sometimes even to 
suicide. A poor prognosis is indicated by yielding (rather than 
resisting) to compulsions, a early onset, male gender, tic related 
forms of OCD with associated to hoarding/symmetry compul-sions, the need for hospitalization, psychotic features, a coexisting major depressive disorder, delusional beliefs, the presence of overvalued ideas (i.e. some acceptance of the obsessions and compulsions), and the presence of personality disorder (especially schizotypal personality disorder).
(22–24) A good prognosis is 
indicated by good social and occupational adjustment and less avoidance.

(21) The obsessional content does not seem to be related 
to the prognosis, except for hoarding, which is usually considered to have a less favourable outcome.
Aetiology
Neurotransmitters
Many clinical trials of various serotonergic drugs lend support to the hypothesis that a dysregulation of serotonin is involved in the beneﬁ  cial therapeutic effect in OCD. However, this does not neces-
sarily reﬂ  ect on pathogenesis. Abnormality of the serotonergic 
system, and particularly the hypersensitivity of postsynaptic 5-HT receptors, constitutes the leading hypothesis for the underlying pathophysiology of OCD.
(7,25–38) However, a potential role for 
dopamine has been emerging as well.(39)
Clinical studies have assayed cerebrospinal levels of serotonin 
metabolites (e.g. 5-hydroxyindoleacetic acid [5-HIAA] a 5-HT metabolite that serves as an index of 5-HT turnover)
(25,26)  and

(25,26)  and 
afﬁ nities of imipramine and paroxetine(40) binding sites on plate-
lets show that it binds to serotonin reuptake sites,(27–30) in some 
studies of OCD patients. A study supporting the relationship between a decreased function of the serotonergic system and a positive response to selective serotonin reuptake inhibitors (SSRIs), demonstrated normalization of the number of platelet5-HT transporters following treatment with different SSRIs.
(31)
In an earlier study, patients who responded to clomipramine had higher pretreatment levels of 5-HIAA than the non-responders.
(25)
Moreover, the clinical improvement was positively correlatedwith a decrease in the concentration of 5-HIAA in cerebrospinal ﬂ uid.
(25)
Another approach is to examine peripheral measures of seroto-

(25)
nergic and noradrenergic function in patients with OCD. In one study, clinical improvement during clomipramine therapy closely correlated with pretreatment platelet serotonin concentration and monoamine oxidase activity, as well as with the decrease in both measures during clomipramine administration.
(32) Moreover, only 
the plasma levels of clomipramine (a potent 5-HT reuptake inhibi-tor), but not the plasma levels of its primary metabolite, desmethyl clomipramine (which has noradrenergic properties), correlated signiﬁ  cantly with an improvement in OCD symptoms. These 
ﬁ ndings suggest that the effects of anti-obsessive medications,

ﬁ ndings suggest that the effects of anti-obsessive medications, 
clomipramine in this study, on serotonin function are pertinent to the anti-obsessional action observed.Additional support for the importance of serotonin in the 
therapeutic response to serotonin reuptake inhibitors (SRIs) in OCD came from a study by Benkelfat et al .
(38) in which the
investigators administered the serotonin receptor antagonist metergoline and placebo to 10 patients with OCD in a double-blind crossover study. Patients receiving clomipramine on along-term basis responded with greater anxiety to a 4-day admin-istration of metergoline when compared with the placebo phase of the study.
Additional evidence for disturbances of the serotonergic 
system in OCD was provided by challenge studies. Challenges with l-tryptophan,
(33)m-chlorophenylpiperazine (mCPP),(7,34) sumat-
riptan (a 5-HT1D agonist(6)), ipsapirone (a 5-HT1A receptor 
ligand(35)), and MK-212 (a 5-HT1A and 5-HT2C agonist(36)),

ligand(35)), and MK-212 (a 5-HT1A and 5-HT2C agonist(36)), 
among others, were used to evaluate whether they worsen obsessive–compulsive symptoms or whether they elicit different physiological responses (thermal or neuroendocrine) in patients with OCD com-pared with controls. Only two compounds ( m-chlorophenylpiper-
azine and sumatriptan) have shown behavioural hypersensitivity and neuroendocrine hyposensitivity to be characteristic of serotonergic challenges in patients with OCD. These studies may have the potential to pinpoint the receptor subtype involved in OCD, raising the possibility that 5-HT
1B (but not 5-HT1A) could 
be involved in OCD.(37)
Dopamine

Dopamine
The most compelling evidence for dopaminergic involvement in OCD comes from the abundance of OCD symptoms in basal ganglia disorders, such as T ourette’s syndrome, Sydenham’schorea, and postencephalitic parkinsonism. The therapeuticbenefits obtained with the coadministration of dopamineblockers and SRIs in a subset of patients with both OCD and ticdisorder
(41) has also suggested a role for dopamine dysfunction. 
A study evaluating levels of platelet sulphotransferase, an enzyme involved in the catabolism of catecholamines (providing a mark-er of presynaptic dopamine function), reported a decreased level of platelet [
3H]imipramine binding and a parallel increase in
the level of sulphotransferase activity in OCD compared with controls. This provides further support for the hypothesisof reduced 5-HT activity and increased dopamine transmission in OCD.
(28,39)
Immune factors

(28,39)
Study of autoimmune factors has been prompted by the associa-tion of OCD and the autoimmune disease of the basal ganglia, Sydenham’s chorea. This complication of rheumatic fever is accom-panied by obsessive–compulsive symptoms in over 70 per cent of cases
(42): 10 out of 11 children had antibodies directed against the 
caudate.(42) These children had a history of obsessive–compulsive 
symptoms, which started prior to the onset of the chorea, reached a peak in line with the motor symptoms, and declined with their resolution. This is consistent with the hypothesis of basal ganglia dysfunction in OCD.
Antibodies against two peptides of the basal ganglia have also 
been found.
(43) A strong connection was reported between OCD/
T ourette’s syndrome and the B-cell antibody D8/17, which is another antibrain antibody.
(44) The speciﬁ  city of these antibodies

(44) The speciﬁ  city of these antibodies 
to OCD, as well as the generalizability of these rare cases, is as yet unclear.4.8 obsessive–compulsive disorder

SECTION 4  clinical syndromes of adult psychiatry 768
Brain imaging studies
The use of positron emission tomography has demonstrated the 
presence of increased activity (i.e. metabolism and blood ﬂ  ow) in 
the frontal lobes, the basal ganglia (especially the caudate nucleus), and the cingulum of patients with OCD.
(45) Pharmacological and 
behavioural treatments reportedly reverse those abnormalities.(46)
The data from functional imaging studies are consistent with the data from structural brain imaging studies. Both CT and magnetic resonance imaging studies have found decreased sizes of caudate bilaterally. Both functional and structural imaging procedures are also consistent with the observation that neurological procedures involving the cingulum are sometimes effective in the treatment of patients with OCD.
Overall, the brain imaging research suggests a role for the

Overall, the brain imaging research suggests a role for the 
prefrontal cortex-basal ganglia thalamic circuitry. Dysfunction of these circuits can be explored by neuropsychological testing and recording evoked potentials. Indeed, a study of patients with OCD demonstrated that they are slower in performing tasks involving frontocortical systems, suggesting alterations at this level.
(47)
An evoked potential study showed enhanced processing negativity in the frontal cortex consistent with the prefrontal hyperactivity shown in brain imaging studies.
(48) Moreover, the reﬂ  ection of 
behavioural challenge on brain activity (brain responsivity) may be a potential tool for predicting a response to successful intervention with SSRI.
(49)
Genetics
A signiﬁ  cantly higher concordance rate was found for monozygotic 
twins than for dizygotic twins.(50) Of the ﬁ  rst-degree relatives of 
patients with childhood-onset OCD, 35 per cent are also afﬂ  icted

patients with childhood-onset OCD, 35 per cent are also afﬂ  icted 
with the disorder.(51) Although this high rate is possibly related to 
the early-onset subtype, it nevertheless suggests a genetic compo-nent in OCD. Genetic research has yet to ﬁ  nd abnormalities at the 
5-HT transporter gene level. A study exploring the polymorphism of the promoter region of the gene for the 5-HT transporter failed to identify any differences between patients with OCD and controls.
(52) However, several studies found polymorphism 
of 5HT1Bβ in OCD,(53,54) hence providing further support for the 
5HT1B involvement in OCD.
Other biological data
Sleep electroencephalography and neuroendocrine studies have found abnormalities similar to those seen in depression, such as decreased rapid eye movement latency, non-suppression on the dexamethasone suppression test, and decreased growth hormone secretion with clonidine infusions.
(55,56)

(55,56)
Behavioural factors
According to the learning theory, obsessions can be considered 
conditioned stimuli. When a relatively neutral stimulus is coupled 
with an anxiety-provoking stimulus, through conditioning, it will 
produce anxiety even when presented alone. In this regards, even 
the thought of the anxiety-provoking stimulus can cause anxiety, 
similarly to Pavlov’s dog, which salivated even before he actually had food. Consequently, avoidant behaviour is being adopted in order to avoid the anxiety-prov oking stimulus and any other stimuli, 
which remind it. The compulsions are learnt as a way to reduce anxiety. Once producing a relief of the anxiety, the relief serves as reinforce to the compulsion, which are then being repeated by the 
patient. Through the process of conditioning, reward and rein-forcement, rituals, and avoidant strategies are become ﬁ  xed.
The dynamic aspects of OCD were ﬁ  rst described by Sigmund

The dynamic aspects of OCD were ﬁ  rst described by Sigmund 
Freud, who coined the term ‘obsessional neurosis’ . The disorder was thought to result from a regression from the Oedipal phase to the anal phase, with its characteristic ambivalence. The coexistence of hatred and love towards the same person leaves the patient paralyzed with doubt and indecision. Freud originally suggested that obsessive symptoms result from unconscious impulses of an aggressive or sexual nature. These impulses cause extreme anxiety, which is avoided by the defence mechanisms. One of the striking features of patients with OCD is the degree to which they are preoccupied with aggression or cleanliness (anal phase), either overtly in the content of their symptoms or in the underlying associations.
Freud described three major psychological defence mechanisms 
that are important in OCD: isolation, undoing, and reaction

that are important in OCD: isolation, undoing, and reaction 
formation. According to the psychoanalytical formulation, OCD develops when these defences fail to contain the anxiety. Isolation is the separation of the idea and the affect that it arouses. Undoing is a secondary defence to combat the impulse and quit the anxiety that its imminent eruption into consciousness arouses. Undoing is a compulsive act, performed to prevent or undo the results that the patient irrationally anticipates from a frightening obsessional thought or impulse. Reaction formation is related to the produc-tion of character traits rather than symptom formation (character-istic of the above defences). The trait seems highly exaggerated and inappropriate (i.e. the switch of anger and hate into exaggerated love and dedication).
Summary
The efﬁ  cacy of the SRIs for OCD, together with the lack of efﬁ  cacy

Summary
The efﬁ  cacy of the SRIs for OCD, together with the lack of efﬁ  cacy 
of adrenergic antidepressants, has suggested that serotonin is involved in the pathophysiology of OCD. This relationship was validated by research on serotonergic markers in OCD and by the challenge paradigm.
(6) Which type of serotonergic receptor is 
involved in the pathogenesis and/or the mechanism of action of anti-obsessional drugs, is still unclear. However, the possible role of 5HT
1B has emerged. Further studies are crucial for elucidating 
the role of serotonin and other neurotransmitters (i.e. dopamine) in the pathophysiology and management of OCD.
The pharmacological treatment of OCD
Since the early 1980s, several potent SRIs have been studied exten-sively in OCD. Aggregate statistics for all SRIs suggest that 70 per cent of treatment-naive patients will improve at least moderately.
(57)
Efﬁ cacy of serotonergic versus adrenergic 
antidepressants

(57)
Whilst anecdotal reports have suggested that clinical beneﬁ  t can be 
obtained with a range of reuptake blockers, effectiveness has only been demonstrated consistently for the SRIs. Several studies have directly compared clomipramine with other antidepressants with a consistent ﬁ  nding: antidepressant drugs that are less potent SRIs 
than clomipramine are generally ineffective in OCD.
(7–9,25)

769
In the late 1960s, clomipramine was the ﬁ  rst reported effective 
medication for OCD.(4,5) Since then, numerous placebo-controlled 
studies have clearly shown clomipramine’s effectiveness, and this has been conﬁ  rmed in a United States multicentre controlled trial 
(n = 520).
(58) In this study, after 10 weeks of treatment, 58 per cent 
of patients treated with clomipramine rated themselves much or very much improved versus 3 per cent of placebo-treated patients.
Besides the SRI clomipramine, the newer non-tricyclic SSRIs, 
such as ﬂ  uoxetine, ﬂ  uvoxamine, paroxetine, sertraline, citalopram, 
and escitalopram are gaining acceptance as effective alternatives for the treatment of OCD in controlled studies. Actually, they were found to be as effective as clomipramine.
(59–62) Since SSRIs are less 
toxic in case of overdose, and as they have less cholinergic side-effects, they are considered as a ﬁ  rst-line treatment for OCD.
(a) Onset of treatment response

It has been suggested that a relatively long period, up to 8 or even 
12 weeks, is needed before one can consider a serotonin reuptake inhibitor to be ineffective. Several months’ treatment is often needed to achieve a maximum response.
(b) Long-term treatment
Most patients relapse after prematurely discontinuing treatment, but, as stated above, it may take many months for a maximum response to be seen. Pato et al.
(63) reported that 16 out of 18 patients 
with OCD relapsed within 7 weeks after stopping clomipramine, although some had been treated for more than a year (mean, 10.7 months). All patients regained the therapeutic effects when clomipramine was reintroduced. Leonard et al .
(9) examined the

(9) examined the 
effect of clomipramine substitution during a long-term clomip-ramine treatment in 26 children and adolescents with OCD (mean duration of treatment was 17 months). Half the patients were blindly assigned to 2 months of desipramine treatment, and then clomipramine was reintroduced. Almost 90 per cent relapsed during the 2 months’ substitution period compared with only 18 per cent of those kept on clomipramine throughout the study. Therefore, it seems advisable that patients with OCD should be maintained on anti-obsessive medications for a long period, and certainly for more than a year before a very gradual attempt is made to discontinue the treatment.
The maintenance dose needed in OCD is also unclear. In a study 
that examined this issue, Mundo et al.
(64) investigated the effect of 
dose reduction in patients previously treated successfully with ﬂ uoxetine. Patients were randomized to receive the same drug

dose reduction in patients previously treated successfully with ﬂ uoxetine. Patients were randomized to receive the same drug 
dosage or to receive a reduced dose. It appears that ‘the dose that makes you well keeps you well’; i.e. that medium to high doses of SRIs are required.
(c) Drug dosage
Higher doses of SSRIs have been used in the treatment of OCD as compared to treatment of depression. Two ﬁ  xed-dose studies using 
ﬂ uoxetine and one pan-European study with paroxetine have found 
some advantage with using higher doses, and those effects were found with citalopram and escitalopram studies.
(6,37,62,65–67)
A theoretical basis for this clinical ﬁ  nding, which is related to the 
‘stickiness’ of the 5HT1B receptor has been reported.(67,68)
Comparative studies of clomipramine versus SSRIs

The introduction of SSRIs has raised the question regarding the comparative efﬁ  cacy of clomipramine versus that of the SSRIs. SSRIs are important alternatives to clomipramine, since their range 
of side-effects is different (absence of anticholinergic side-effects, sedation, safety with overdose, etc.). Although SSRIs may be associ-ated with sexual side-effects, headaches, and appetite disturbances, these side-effects are usually less troublesome as compared to clomipramine’s side-effects.
Fluoxetine was compared with clomipramine in 11 patients with 
OCD in a 10-week crossover study.
(69) Although no signiﬁ  cant 
differences were noted regarding clinical efﬁ  cacy, the proportion of 
ﬂ uoxetine non-responders who later responded to clomipramine

ﬂ uoxetine non-responders who later responded to clomipramine 
tended to be higher compared with the clomipramine non-responders who were switched to ﬂ  uoxetine. However, patients 
reported significantly fewer side-effects while on fluoxetine. Freeman et al .
(70) compared the efficacy of fluvoxamine and 
clomipramine in a multicentre randomized double-blind parallel-group comparison in 66 patients. Both drugs were equally effective and well tolerated, but ﬂ  uvoxamine produced fewer anticholinergic 
side-effects and caused less sexual dysfunction than clomipramine, but more reports of headache and insomnia.
Paroxetine was of comparable efﬁ  cacy to clomipramine and 
both were signiﬁ  cantly more effective than placebo in a multi-
national double-blind placebo-controlled parallel group study of 399 patients with OCD.

(71) Bisserbe et al .(72) reported that 
sertraline (50–200 mg/day) was signiﬁ  cantly more effective than 
clomipramine (50–200 mg/day) in a double-blind study ( n = 160).
Other pharmacological approaches and neurosurgery
Considered as one of the anxiety disorders according to DSM-IV 
(but not according to the ICD-10), it is not surprising that anxio-lytics have been suggested for the treatment of patients with OCD. Thus, clonazepam has been reported as efﬁ  cient in several uncon-
trolled studies and case series, and even in a small double-blind randomized multiple crossover study. However, since OCD is a chronic disorder, the long-term use of anxiolytics raises questions of dependency.
Despite reports in open studies regarding the efﬁ  cacy of trazo-

done, buspirone, and lithium, results from double-blind studies proved negative. Adding drugs that affect dopamine function, especially the atypical antipsychotics (i.e. risperidone or quetiap-ine), to SRI therapy in patients with treatment-resistant OCD, may result in improvement for patients with a personal or family 
history of tics.
(53) A combination of SSRI and small doses of high 
potent dopamine blocker (haloperidol or pimozide) was found to be useful for both the tics and the OC symptoms.
(73)
Neurosurgery and Deep Brain Stimulation (DBS)  have been 
reported to be effective in some patients with OCD. Neurosurgery involves procedures that disconnect the outﬂ  ow pathways originat-
ing from the orbitofrontal cortex. Cingulotomy can help some intractable patients, but although the immediate results may be striking, the long-term prognosis is more reserved.
(74) As for DBS,

(74) As for DBS, 
initial reports are optimistic(75) but as the total number of patients 
who underwent this procedure is very small, its efﬁ  cacy needs to be 
further elucidated.
Summary of drug treatment for OCD
The ﬁ  rst-line treatment consists of either an SSRI or clomipramine. 
Any one of the six SSRIs (ﬂ  uoxetine, ﬂ  uvoxamine, paroxetine, 
sertraline, citalopram, escitalopram) in current use constitutes an effective and safe choice, but choosing which SSRI depends on the 4.8 obsessive–compulsive disorder

SECTION 4  clinical syndromes of adult psychiatry 770
drug’s pharmacokinetic proﬁ  le, as well as the physician’s familiarity 
with the drug. The dose should be higher than that used for treat-ing depression (e.g. 40–60 mg of ﬂ  uoxetine) and the trial should 
last at least 12 weeks. If clomipramine is chosen, cardiovascular problems and closed-angle glaucoma should ﬁ  rst be ruled out. 
Doses of 200 to 300 mg of clomipramine are needed, but titration should last for 1 to 3 weeks and the optimal dose should be contin-ued for at least 12 weeks before determining a lack of response.
If the patient cannot tolerate the ﬁ  rst drug (an SSRI) or did not 
respond, a trial of another SSRI or CMI is advised or augmentation (i.e. risperidone) is recommended.
The third stage in non-responders, and in cases of only a partial

The third stage in non-responders, and in cases of only a partial 
response, includes small doses of antipsychotics (especially in T ourette’s syndrome), or the addition of lithium or trazodone, buspirone, or tryptophan. The fourth stage consists of atypical neuroleptics, thyroid supplementation, clonidine, a monoamine oxidase inhibitor, and intravenous clomipramine. In truly severe and resistant cases, neurosurgery or DBS could be tried.
Psychological approaches
The effect of a psychodynamic approach in OCD is limited, whereas modern interventions like cognitive and behavioural therapy show promising results.
(76) Behavioural therapy was found to be effective 
in OCD,(76,77)  and some data indicate that the beneﬁ  cial effects 
of behavioural therapy may be longer lasting.(78) About two-thirds

of behavioural therapy may be longer lasting.(78) About two-thirds 
of patients with moderately severe rituals can be expected to improve substantially, but not completely. A combination of behav-ioural therapy and pharmacotherapy may constitute the optimal treatment for OCD. Recently, two neuroimaging studies found that patients with OCD who are successfully treated with behavioural therapy show changes in cerebral metabolism similar to those produced by successful treatment with SRIs.
(47,79)
Behavioural therapy can be conducted in in- and outpatient 
settings. The principal behavioural approaches in OCD are expo-sure for obsessions and response prevention for rituals (see Chapter 6.3.2.1). Desensitization, thought stopping, ﬂ  ooding, implosion

settings. The principal behavioural approaches in OCD are expo-sure for obsessions and response prevention for rituals (see Chapter 6.3.2.1). Desensitization, thought stopping, ﬂ  ooding, implosion 
therapy, and aversion conditioning have also been used in patients with OCD. In behavioural therapy the patient must collaborate and perform assignments. In a study of 18 patients with OCD , those 
who received exposure and response prevention therapy showedsigniﬁ  cant improvement, whereas patients on a general anxiety 
management intervention (control) showed no improvement from baseline.
(80) Direct comparisons of behavioural therapy and phar-
macotherapy are few and are limited by methodological issues.
In thought stopping, the patient (or initially the therapist) shouts 
‘stop’ or applies an aversive stimulus to counteract the obsessional preoccupation. The patient may also imagine a stop sign with a police ofﬁ  cer nearby or another image that evokes inhibition at the

same time that he or she recognizes the presence of the obsession. Another technique is to ‘postpone’ the thought until a speciﬁ  ed 
time (e.g. an hour later) and not to think about it until then.
Psychological factors might be of considerable beneﬁ  t in under-
standing what precipitates exacerbations of the disorder and in treating various forms of resistances to treatment, such as non-compliance to medications or to homework assignments. It is important to remember that the symptoms may have impor-
tant psychological meanings that make patients reluctant to give 
them up.In the absence of controlled studies of insight-oriented psycho-
therapy for OCD, the anecdotal reports reporting lasting change do not allow generalizations to be made regarding efﬁ  cacy. Also, 
the efﬁ  cacy of medications in producing quick improvement has 
rendered slow and long-term psychotherapy out of favour.
Supportive psychotherapy has a non-speciﬁ  c place in managing

Supportive psychotherapy has a non-speciﬁ  c place in managing 
patients with OCD, and may help patients improve their function-ing and adjustment. The management plan should also include attention to the family members through the provision of emotional 
support, reassurance, explanation, and advice on how to manage and respond to the patient. Family therapy may reduce marital discord and build a treatment alliance, as well as helping in the resistance to compulsions. Group therapy is useful as a support system for some patients.
Summary

Summary
The treatment of OCD was characterized by pessimism until 25 years ago when effective treatments including behavioural therapy and the serotonin reuptake inhibitors were developed. Although introduced for OCD in 1967, it was only in the 1980s that double-blind studies conﬁ rmed the efﬁ  cacy of clomipramine, an SRI. This was followed by 
the introduction of the selective serotonin reuptake inhibitors, which also proved effective for OCD. The anti-obsessive activity of these drugs was found to be independent from the drugs’ antidepressant effect, as established by their efﬁ  cacy both in depressed and non-
depressed patients. Overall, serotonergic therapies have provided a better outlook for these patients and have contributed to our under-standing of the pathophysiology of OCD.
(6,7) Previously thought to

(6,7) Previously thought to 
be a rare and untreatable disorder, OCD is now recognized as com-mon, and there is good reason to expect that patients with OCD will beneﬁ  t substantially from potent SRIs and behaviour therapy.
Many patients with OCD do not seek treatment and the disease 
tends to be chronic. There is about a 10-year lag between the onset of symptoms and the seeking of professional help due to feelings of embarrassment. Further delay ensues until the diagnosis and correct treatment are given.
(81) Census data suggest that over $8 billion are 
spent in the United States each year on the management of OCD, one-ﬁ fth of that spent on cardiac disease.
(82) Because patients with OCD 
often attempt to conceal their symptoms, it is incumbent on clinicians to screen for OCD in every mental status examination, since appro-priate treatment can result in improved quality of life, reduced OCD chronicity, and a decrease in cost to the individual and society.

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Psychopharmacology ,16, 75–86.
67. El Mansari, M. and Blier, P . (2006). Mechanisms of action of current 
and potential pharmacotherapies of obsessive-compulsive disorder. Progress in Neuro-Psychopharmacology & Biological Psychiatry ,
30, 362–73.
68. Blier, P . and Szabo, S.T. (2005). Potential mechanisms of action 
of atypical antipsychotic medications in treatment-resistant depression and anxiety. The Journal of Clinical Psychiatry ,66(Suppl. 8), 
30–40.
69. Pigott, T.A., Pato, M.T., Bernstein, S.E., et al. (1990). Controlled

30–40.
69. Pigott, T.A., Pato, M.T., Bernstein, S.E., et al. (1990). Controlled 
comparisons of clomipramine and ﬂ  uoxetine in the treatment of 
obsessive-compulsive disorder: behavioral and biological results. Archives of General Psychiatry ,47, 926–32.
70. Freeman, C.P .L., Trimble, M.R., Deakin, J.F.W., et al. (1994). 
Fluvoxamine versus clomipramine in the treatment of obsessive 
compulsive disorder: a multi-center, randomized, double-blind, 
parallel group comparison. The Journal of Clinical Psychiatry ,
55, 301–5.
71. Zohar, J. and Judge, R. (1996). Paroxetine versus clomipramine in the 
treatment of obsessive-compulsive disorder. The British Journal of 
Psychiatry ,169, 468–74.
72. Bisserbe, J.C., Lane, R.M., Flament, M.F., et al. (1997). A double-blind 
comparison of sertraline and clomipramine in outpatientswith obsessive-compulsive disorder. European Psychiatry ,
153, 1450–4.
73. McDougle, J., Goodman, W.K., Price, L.H., et al. (1990). Neuroleptic

73. McDougle, J., Goodman, W.K., Price, L.H., et al. (1990). Neuroleptic 
addition in ﬂ  uvoxamine-refractory obsessive-compulsive disorder. 
The American Journal of Psychiatry ,147, 652–4.
74. Jenike, M.A., Baer, L., Ballantine, T., et al. (1991). Cingulotomy for 
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outcomes in deep brain stimulation for highly resistant obsessive-
compulsive disorder. Neuropsychopharmacology .31, 2384–93.
76. Van Balkom, A.J.L.M., De Haan, E., Van Oppen, P ., et al. (1998). 
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chronic obsessive-compulsive neurosis in vivo  exposure: a 2-year

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follow-up and issues in treatment. The British Journal of Psychiatry ,
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773
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changes in cerebral glucose metabolic rate after successful behavior 
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81. Hollander, E. (1997). Obsessive compulsive disorder: the hidden 
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obsessive compulsive disorder. Medical Interface ,8, 102–9. 4.8 obsessive–compulsive disorder

4.9
Depersonalization disorder
Nick Medford, Mauricio Sierra, 
and Anthony S. David
Depersonalization , a term coined by Dugas in 1898,(1) is deﬁ  ned 
in DSM-IV as ‘an alteration in the experience of self so that one feels detached from and as if one is an outside observer of one’s outside mental processes or body’ . Brief, self-limiting experiences of depersonalization commonly occur in healthy people in the context of fatigue, intense stress, or during/after intoxication with alcohol or illicit drugs. However, some people experience chronic depersonalization of a disturbing intensity, causing signiﬁ  cant dis-
tress and impacting on quality-of-life and daily functioning. This may occur as a primary depersonalization disorder (DPD) , or in 
the context of other psychiatric or neurological conditions. In this chapter, we consider the primary disorder, although some sections are also relevant to secondary depersonalization.

The depersonalization experience is one of feeling strangely 
altered and unreal, in a way that sufferers often ﬁ  nd very hard to 
convey. It is often accompanied by the related phenomenon of 
derealization , in which the person’s surroundings are experienced 
as somehow remote and lacking immediacy and vibrancy, as if the world itself has become oddly unreal. Patients with persistent depersonalization and derealization often use the analogy of feel-ing as if they are on the set of a play or ﬁ  lm, where nothing is real 
and they are acting out a role rather than living a real life.
The diagnosis requires the presence of persistent, distressing deper-sonalization and/or derealization, occurring in clear consciousness, and not due to another disorder or substance. Some patients ﬁ  nd

it impossible to divide their symptoms into depersonalization and derealization, seeing them as essentially two ways of describing the same experience. Nevertheless, one may encounter patients who describe one without the other. ‘Pure’ derealization is, however, uncommon.
In addition, there are a number of other symptoms that occur 
with sufﬁ  cient frequency to be considered as part of the deperson-
alization syndrome, although their presence is not essential for making the diagnosis. These are as follows:
Desomatization —a loss or diminution of bodily sensation, 
sometimes accompanied by a feeling of disembodiment.De-affectualization— a loss or diminution of emotional reactivity- 
the feeling that life has somehow been drained of emotional con-tent, or that the sufferer feels little emotion in response to people or events that would normally be expected to elicit an emotional response. This may have signiﬁ  cance for intimate relationships. It

should be noted that de-affectualization is not usually accompanied by blunted affect of the type commonly seen in schizophrenia.
De-ideation —a feeling of mental emptiness which may cause 
difficulty in concentrating, a distorted experience of time, and a sense of detachment from memories. Often accompanied by a feeling of ‘stufﬁ  ness in the head’ or ‘as if my brain has turned to cotton 
wool’ .
While ‘depersonalization’ and ‘derealization’ are well-established 
in the psychiatric lexicon, the three terms listed above are not widely used or discussed. However, a recent analysis of symptoms report-ed by patients with DPD gave strong support to the idea that the condition should be considered as a syndrome, with symptoms occurring in domains corresponding to the terms used above.
(2)
In DSM-IV , DPD is classiﬁ  ed as a dissociative disorder, while in

(2)
In DSM-IV , DPD is classiﬁ  ed as a dissociative disorder, while in 
ICD-10 it falls under the vague heading of ‘other neurotic disorders’ , and is not linked to any other category of disorder.
It has been argued that DPD is not truly a dissociative disorder, 
as dissociation is generally characterized by a lack of subjective awareness of change, whereas in DPD the experience of feeling changed is central. However, this apparent contradiction can be resolved if dissociation is concep tualized as a categ ory inc orporating
both types of phenomenon.
(3)
The diagnosis should be established by a careful clinical assessment. Because DPD remains a somewhat obscure disorder, patients with this condition may have had unproductive consultations with other professionals and formed the impression that their symptoms are bafﬂ ing, perhaps even unique. Being given the correct diagnosis

and the opportunity to discuss it in depth with an informed psy-chiatrist may come as a great relief. The reassurance derived from this may in itself have a powerful therapeutic effect.

775
Where there are other psychiatric symptoms (e.g. anxiety, panic 
attacks, depressive features), the distinction between primary and secondary depersonalization may be difﬁ  cult. The best way to 
approach this is simply to establish what the dominant symptoms are at the time of presentation. In a patient with a history of panic disorder who has developed severe unremitting depersonalization, and now has very infrequent panic attacks, the most pragmatic approach is to diagnose DPD. The fact that the panic symptoms preceded the onset of DPD is less important than the fact that it is now the DPD symptoms that dominate the clinical picture.
This issue aside, the main psychiatric differential hinges on the

This issue aside, the main psychiatric differential hinges on the 
possibility that when patients describe feeling altered or unreal, they are articulating delusional beliefs. It is important to establish that patients have no psychotic symptoms; in particular, that they do not literally believe themselves to be unreal or dead, as this is suggestive of psychotic depression and the Cotard delusion, rather than DPD.
Depersonalization can also occur in neurological disorders, 
principally temporal lobe epilepsy and migraine.
(4) Here the history 
is usually of brief, stereotyped episodes, with associated features that should provide sufﬁ  cient clues to the underlying diagnosis.
Until recently, DPD was considered rare, but contemporary epide-
miological work suggests that it affects 1–2 per cent of the general adult population,
(5) with a gender ratio of 1:1.
Symptom surveys suggest that depersonalization is perhaps the

Symptom surveys suggest that depersonalization is perhaps the 
third commonest symptom (after anxiety and low mood) in psy-chiatric populations. It should be noted that these studies do not distinguish between primary and secondary depersonalization.
Aetiology
Various factors have been implicated in the genesis and mainte-nance of the condition. Biological and psychological issues are considered separately here, but should not be seen as mutually exclusive.
Psychological factors : Many patients with primary DPD have

Psychological factors : Many patients with primary DPD have 
concurrent anxiety or mood symptoms, or a previous history of anxiety and/or panic attacks. The clinical impression is often that feelings of detachment and unreality have arisen as a defence against feeling anxious and threatened—a way of keeping a stressful world at a safer psychological distance. There is sometimes a history of DPD symptoms ﬁ  rst occurring in the context of some particu-
larly stressful event or period. Often, however, speciﬁ  c precipitants 
are not identiﬁ  able.
Once DPD develops, further anxiety may follow—patients may 
worry that, for example, the peculiar feeling of unreality is a sign

worry that, for example, the peculiar feeling of unreality is a sign 
that they are on the verge of mental breakdown. These concerns often manifest as obsessional rumination and self-monitoring, characterized by a compulsive checking of the inner state and a comparison of this state with some idealized standard of normality. This further anxiety can lead to reinforcement and perpetuation of depersonalization and derealization, so that symptoms feed each other in a ‘vicious circle’ .
Biological factors : There is objective biological evidence relating 
to the loss of emotional reactivity that patients with DPD commonly report. Patients with DPD show attenuated skin conductance responses to emotional stimuli,
(6) while fMRI work suggests that 
the brain’s emotional response circuitry is inhibited in DPD.(7,8)Some 10–20 per cent of patients with DPD describe symptoms

the brain’s emotional response circuitry is inhibited in DPD.(7,8)Some 10–20 per cent of patients with DPD describe symptoms 
beginning during or after an episode of illicit drug use, cannabis being the drug most commonly implicated. Many illicit drugs are known to cause depersonalization phenomena acutely, but it is unclear how any drug might produce chronic symptoms persisting long after the drug is cleared from the system. It seems likely that 
the initial symptoms are due to the drug, but become chronic and unremitting through the kind of “vicious circle” outlined above.
(9)
Two large case series(10,11)  suggest that age of onset is usually in late 
adolescence or early adulthood, although up to a third of patients describe symptoms originating in childhood. Onset may be sudden or gradual, and symptoms thereaft er may be episodic or continuous. 
Patients often report little or no ﬂ  uctuation in symptom nature or

Patients often report little or no ﬂ  uctuation in symptom nature or 
severity, although with close questioning it is often possible to establish that certain factors (e.g. stress, fatigue) worsen the symptoms.
Symptoms are often unremitting for many years. In the largest 
case series to date,
(10) patients had been symptomatic for a mean 
of 13.9 years at the time of initial presentation to a specialist DPD clinic. This striking statistic may, in part, reﬂ  ect the wide-
spread lack of familiarity with the condition and consequent delays in diagnosis.
While there is little available data on which to base predictions 
about prognosis, symptoms that have been continuous for many years tend to be more refractory than those of more recent origin.
Evaluation of treatments
Until recently, the treatment literature consisted of small case series or single case reports, but a few larger studies have now been performed. Key ﬁ  ndings are:

Lamotrigine : Despite encouraging results from a pilot study, a 
placebo-controlled crossover trial did not show evidence of efﬁ  cacy. 
However, in a larger, more recent open-label study of lamotrigine-antidepressant combination therapy, signiﬁ  cant improvements 
were seen in a majority of patients.
(12)
Opioid antagonists : Transient reductions in symptoms have been 
reported in response to naloxone infusion, and a recent open-label study of oral naltrexone showed some evidence of efﬁ  cacy.
(13)
Clomipramine : One small open-label study, results inconclusive.(14)
There remains a paucity of data from rigorous controlled trials. 
T o date, the only large double-blind randomised controlled trial is a study of ﬂ uoxetine , which found no evidence of efﬁ  cacy.
(15)

(15)
Despite a number of reports of successful treatment with a range 
of psychotherapeutic techniques, the only treatment trial is an open study of cognitive behavioural therapy (CBT), which showed signiﬁ  cant clinical beneﬁ  ts.
(16)
It will be appreciated from the above that there is insufﬁ  cient evi-
dence on which to base deﬁ  nitive treatment guidelines, and as yet 4.9 depersonalization disorder

SECTION 4  clinical syndromes of adult psychiatry 776
no drugs are licensed for the treatment of DPD in the UK. Current 
treatment strategies are based on encouraging results from explor-atory studies, rather than on any overwhelming weight of evidence, and this limitation should not be concealed from patients.
The combination of lamotrigine (up to 500 mg per day) and an 
SSRI (usually citalopram or escitalopram) is often used as ﬁ  rst-line 
treatment (see Medford et al. in Further Reading below). An alter-
native is clonazepam (0.5–4 mg per day).There have been no clini-cal trials of clonazepam in DPD, but many patients ﬁ  nd it helpful, 
particularly when there is co-morbid anxiety. The risk of depen-dency must be carefully weighed against possible clinical beneﬁ  ts.
Naltrexone (see above) may also have a role, while clomipramine 
may be helpful when obsessional ruminations are prominent. There is anecdotal evidence to support the use of bupropion in treatment-refractory cases.

CBT may be beneﬁ  cial, either alone or in combination with 
pharmacotherapy. Depersonalization experiences do not readily lend themselves to a cognitive behavioural analysis, but CBT techniques may be helpful in addressing associated anxieties, ruminations, and avoidance behaviours, and use of CBT should be considered whenever any of these features are prominent.
The use of standardized rating scales can assist in diagnosis and 
monitoring response to treatment. The Cambridge Depersonali-zation Scale
(17) is particularly recommended.
In secondary depersonalization, it is usually appropriate to sim-
ply pursue conventional treatment of the primary condition, but if depersonalization becomes severe and disabling it may be neces-sary to treat it more speciﬁ  cally. Treatment of depersonalization in

the context of substance misuse is particularly difﬁ  cult: since most 
drugs of abuse can cause or exacerbate the symptoms, there is gen-erally little point in attempting speciﬁ  c treatment unless abstinence 
has been established.
Mayer-Gross, W. (1935). On depersonalization. British Journal of Medical 
Psychology ,15, 103–22. Classic early monograph, still of relevance.
Medford, N., Sierra, M., Baker, D., et al. (2005). Understanding and treating 
depersonalisation disorder. Advances in Psychiatric Treatment ,11,
92–100. Conceptual and clinical overview by clinicians from the UK’s only specialized DPD clinic.
Schilder, P . (1950). The Image and Appearance of the Human Body. 
New Y ork: International Universities Press. Contains a fascinating 
psychodynamic account of DPD.
Simeon, D. andAbugel, J. (2006). Feeling Unreal: Depersonalization 
Disorder and the Loss of the Self. Oxford University Press, USA. Readable and informative book on the disorder.References

 1. Sierra, M. and Berrios, G.E. (1996) Un cas de depersonnalisation, by 
L.Dugas. Translation and introduction. History of Psychiatry ,7, 451–61.
 2. Sierra, M., Baker, D., Medford, N., et al. (2005). Unpacking the 
depersonalization syndrome: an exploratory factor analysis on the Cambridge Depersonalization Scale. Psychological Medicine ,35, 1523–32.
 3. Holmes, E.A., Brown, R.J., Mansell, W., et al.  (2005). Are there two 
qualitatively distinct forms of dissociation? A review and some clinical implications. Clinical Psychology Review ,25, 1–23.
 4. Lambert, M.V ., Sierra, M., Phillips, M.L., et al. (2002). The spectrum of 
organic depersonalisation: a review plus four new cases. Journal of Neuropsychiatry and Clinical Neurosciences ,14, 141–54.

 5. Hunter, E.C.M., Sierra, M. and David, A.S. (2004). The epidemiology 
of depersonalization and derealisation: a systematic review. Social 
Psychiatry Psychiatric Epidemiology ,39, 9–18.
 6. Sierra, M., Senior, C., Dalton, J., et al. (2002). Autonomic response 
in depersonalization disorder. Archives of General Psychiatry ,59, 833–38.
 7. Phillips, M., Medford, N., Senior, C., et al. (2001). Depersonalization 
disorder: thinking without feeling. Psychiatry Res Neuroimaging ,108,
145–60.
 8. Medford, N., Phillips, M., Brierley, B., et al. (2006) Emotional memory 
in depersonalization disorder. Psychiatry Res Neuroimaging ,148, 93–102.
 9. Medford, N., Baker, D., Hunter, E., et al. (2003). Depersonalization 
following illicit drug use: a controlled analysis of 40 cases. Addiction ,12,
1731–6.

9. Medford, N., Baker, D., Hunter, E., et al. (2003). Depersonalization 
1731–6.
10. Baker, D., Hunter, E., Lawrence, E., et al. (2003). Depersonalization 
disorder: clinical features of 204 cases. British Journal of Psychiatry ,182,
428–33.
11. Simeon, D., Knutelska, M., Nelson, D., et al. (2003). Feeling unreal: 
a depersonalization disorder update of 117 cases. Journal of Clinical 
Psychology ,64, 990–7.
12. Sierra, M., Baker, D., Medford, N., et al. (2006). Lamotrigine as an 
add-on treatment for depersonalization disorder: a retrospective study of 32 cases. Clinical Neuropharmacology ,29, 253–8.
13. Simeon, D. and Knutelska, M. (2005). An open trial of naltrexone 
in the treatment of depersonalization disorder. Journal of Clinical 
Psychopharmacology ,25, 267–270.
14. Simeon, D., Stein, D.J., Hollander, E. (1998). Treatment of
depersonalization disorder with clomipramine. Biological Psychiatry ,

44, 302–03.
15. Simeon, D., Guralnik, O., Schmeidler, J., et al. (2004). Fluoxetine 
therapy in depersonalization disorder: randomized controlled trial. 
British Journal of Psychiatry ,185, 31–6.
16. Hunter, E., Baker, D., Phillips, M., et al. (2005). Cognitive-behaviour 
therapy for depersonalisation disorder: an open study. Behaviour 
Research and Therapy ,43, 1121–30.
17. Sierra, M.and Berrios, G.E. (2000). The Cambridge Depersonalization 
Scale: a new instrument for the measurement of depersonalization. Psychiatry Research ,93, 153–64.

4.10
Disorders of eating
4.10.1 Anorexia nervosa
Introduction: history of ideas
Two different approaches may be discerned in the conceptualiza-
tion of anorexia nervosa.
1 The medicoclinical approach deﬁ  nes the illness in terms of its 
clinical manifestations; the main landmarks were the descrip-tions by William Gull in 1874
(1) and Charles Lasègue in 1873.(2)
2 The sociocultural approach is unlike the more empirical clinical 
approach and takes causation into account by viewing the illness as a response to prevailing social and cultural systems. This was well argued by the social historian Joan Jacobs Brumberg who considers anorexia nervosa simply as a control of appetite in women responding to widely differing forces which may change during historical times.
(3)
There is a strong argument for accepting the original descrip-
tions by Gull and Lasègue as containing the essence of anorexia 
nervosa. They both recognized a disorder associated with severe

(3)
nervosa. They both recognized a disorder associated with severe 
emaciation and loss of menstrual periods, inexplicable in terms of 
recognized physical causes of wasting. They were both extremely 
cautious about the nature of the mental disorder. Gull spoke of a morbid mental state or ‘mental perversity’ , and adopted the more general term anorexia ‘nervosa’ which has persisted until today. Lasègue also referred to ‘mental perversity’ but was bold enough to call the condition ‘anorexie hystérique, faute de mieux’ .It is probably best to seek a balance between the diagnostic 
rectitude of the medicoclinical approach and the malleability of anorexia nervosa in different sociocultural settings. Looking back in historical times, it may well be that the self-starvation and ascet-icism of St Catherine of Siena corresponded to modern anorexia nervosa.

(4) In more recent times the preoccupations of the patients 
have altered so that their disturbed experience with their own body
(5) or their ‘morbid fear of fatness’(6) has become one of the 
diagnostic criteria. Y et this concern with body size was not remarked upon by Gull or Lasègue. This is an argument for concluding that at least the psychological content, and perhaps also the form, of anorexia nervosa are changeable in response to historical times and sociocultural inﬂ  uences.
Screening instruments
The most commonly used screening test in the detection of 
anorexia nervosa is the Eating Attitudes T est ( EAT ).(7) Doubt has,

anorexia nervosa is the Eating Attitudes T est ( EAT ).(7) Doubt has, 
however, been expressed about the predictive value of the EAT in the very populations where its use was introduced, as only a small percentage of the EAT-screened positive scores will have an actual eating disorder. Thus, the EAT has limited usefulness in surveys for detecting anorexia nervosa unless it is supplemented by detailed clinical assessments. There is also a risk of failing to detect cases of anorexia nervosa as it was found that patients currently receiv-ing active treatment were among the non-respondents, presumably because they wished to conceal their disorder.
(8)
Populations surveyed
(a) General population surveys
These are often impracticable when the aim is to detect anorexia nervosa, a relatively uncommon disorder.
(b) Surveys of primary care populations

A useful compromise is that of surveying populations of patients who consult their general practitioners. A Netherlands study was successful because a large population was surveyed (over 150 000) and the general practitioners themselves, after suitable training, were responsible for making the diagnoses.
(9,10)Contents
 4.10.2 Bulimia nervosa

SECTION 4  clinical syndromes of adult psychiatry 778
(c) Populations thought to be more at risk
Surveys of ballet and modelling students were conducted because it 
was thought likely that there would be a high prevalence of anorexia nervosa among them as a result of pressures exerted to sustain a slim ﬁ  gure in keeping with their professional image.
(11,12)
Populations of adolescent schoolgirls have also been surveyed 
as their susceptibility might be raised by virtue of their age, sex, and the frequency of dieting among the school population.
(13)
The most thorough survey of 15-year-old schoolchildren was that conducted in Göteborg, Sweden.
(14)
(d) Surveys based on case registers and hospital records
Data have been obtained on patients referred to inpatient and outpatient psychiatric services, or with the addition of patients who had consulted paediatricians, general medical services, or gynaecologists.
(15,16)
Results of epidemiological surveys
(a) Incidence of anorexia nervosa

(15,16)
The studies which counted only hospitalized patients tended to yield low estimates of the annual incidence of anorexia nervosa 
expressed per 100 000 population (e.g. 0.45 in Sweden
(15)). 
Estimates based on case registers of psychiatric patients similarly 
yielded fairly low incidence rates (e.g. 0.64 in Monroe County, 
New York(15)). The incidence found in community-based studies 
was by far the highest (7.7 in The Netherlands(10) and 8.2 in 
Rochester, Minnesota(17)), presumably because they included the 
less severe cases.
(b) Prevalence of anorexia nervosa in vulnerable populations
A high prevalence rate was found among Canadian ballet students (6.5 per cent) and modelling students (7 per cent).
(11) A similar 
survey in an English ballet school also showed a high prevalence of ‘possible’ cases of anorexia nervosa (7.0 per cent).
(12)
Surveys among schoolgirls have shown a fairly wide variation in

(12)
Surveys among schoolgirls have shown a fairly wide variation in 
prevalence rates, ranging from 0 per cent to 1.1 per cent. In the English studies a consistent difference in prevalence rate was found between private schools (1 per cent) and state schools (0–0.2 per cent).
(13) This social class distinction was not so deﬁ  nite in the 
Swedish study where the overall prevalence of 0.84 per cent of schoolgirls, up to and including 15 years of age, represents a high rate for anorexia nervosa.
(14)
(c) Age and sex
Epidemiological surveys have conﬁ  rmed clinical opinion that 
anorexia nervosa commences most frequently in the young, especially within a few years of puberty. The peak age of onset is 18 years.
(13) The illness is less common before puberty, but in a 
series of patients admitted to a children’s hospital the age of onset ranged from 7.75 to 14.33 years.

(18) A prevalence of 2.0 per cent in 
females aged 18 to 25 was found in a community survey in Padua, Italy.
(19)
A marked predominance of females over males is usually reported 
in surveys, for example 92 per cent in North-east Scotland(15) and 
90 per cent among the children in Göteborg.(14) On the other hand 
a community survey in the province of Ontario gave rise to a more balanced female to male ratio (2:1) when cases of partial anorexia nervosa were included.
(20)(d) Social class and socio-economic status
The view has been widely held that anorexia nervosa occurs predominantly in patients with middle-class backgrounds, since Fenwick’s classical observation that anorexia nervosa ‘is much more common in wealthier classes of society than amongst those who have to procure their bread by daily labour’ .
(15)

(15)
Epidemiological surveys aimed at wider populations leave the 
question of social class distribution somewhat equivocal. Whereas a high percentage of combined social classes 1 and 2 (Registrar General’s categories) were found in clinical studies,
(21) a high 
social class predominance was not found in studies utilizing case registers.
(15) On the other hand, the schoolgirl studies mentioned 
above tended to conﬁ  rm a high social class predominance.
Has the incidence of anorexia nervosa increased since 
the 1950s?
From the 1970s experienced clinicians have expressed their view 
that anorexia nervosa had increased in frequency. This view gained 
support from surveys repeated on the same population after inter-vals of 10 years or more in Sweden, Scotland, Switzerland, and Monroe County, New Y ork.
(15) Most investigations found a clear 
trend for an increased incidence over time although it appears that a plateau was reached in the 1980s.
(16) In the most thorough study,

(16) In the most thorough study, 
from Rochester, Minnesota(17) the increase was conﬁ  ned to female 
patients aged 15 to 24 years. There were similar ﬁ  ndings from 
the Netherlands with a rise from 56.4 to 109.2 per 100 000 among 15- to 19-year-old females from 1985–1989 to 1995–1999.
(10)
Although there is support for an increased incidence of anorexia nervosa, there remain dissenting voices.
It is better to pose a different question which renders any contro-
versy unnecessary. We should ask instead whether there has been an increase in the incidence of eating disorders including anorexia nervosa. This is especially relevant in view of the fact that bulimia nervosa is a variant of anorexia nervosa.
(22) There is strong evi-
dence that bulimia nervosa is a new disorder and has not simply appeared because of improved medical recognition.

(23) Moreover, 
the incidence of bulimia nervosa has risen sharply at least until the mid 1990s, so that it is now about double that of anorexia nervo-sa
(24) (see also Chapter 4.10.2). In conclusion, it is clear that since 
the 1960s there has been a signiﬁ  cant increase in eating disorders, 
of which the two clearest syndromes are anorexia nervosa and bulimia nervosa.
Aetiology
Aetiological concepts
According to one robust opinion, it is essential to pursue the search for a speciﬁ  c and necessary cause of anorexia nervosa because the

Aetiology
According to one robust opinion, it is essential to pursue the search for a speciﬁ  c and necessary cause of anorexia nervosa because the 
currently popular ‘multifactorial’ approach has little explanatory power. Accordingly the failure to identify a necessary causal element is regrettable. Many of the factors within a wide range of psychological, social, and physical causes so far studied may therefore only be relevant in predisposing to anorexia nervosa, whose causes still elude clariﬁ  cation’ .
(25)
The multidimensional approach to anorexia nervosa
It is precisely because we do not know the fundamental (necessary) 
cause of anorexia nervosa that recourse has to be had to a multi-

779
dimensional approach, faute de mieux. Although it has its limita-
tions, a multidimensional approach permits one to consider a 
range of possible causal factors which not only act in an additive 
manner but may combine in a speciﬁ  c way to bring about the ill-
ness: ‘It is the interaction and timing of these phenomena in a given 
individual which are necessary for the person to become ill’ .(26)
It is useful to provide a simple model of the way that two broad 
sets of factors may interact and augment each other (Fig. 4.10.1.1). 
The outer circle represents the entire population in a developed 
‘westernized’ country. Within the circle there is a large sector 
representing females within an age range of 10 to 50 years who 
experience prevailing social pressures to acquire a slender body 
shape through dieting. Evidently only a small proportion of these 
women develop the illness. It is likely that for anorexia nervosa to

women develop the illness. It is likely that for anorexia nervosa to 
develop it is also necessary to possess a genetic predisposition, 
represented by the small inner circle. The intersection of the inner 
circle and the large sector produces a small sector of females who 
have the genetic predisposition and also experience sociocultural 
pressures to lose weight, interacting to cause clinical anorexia 
nervosa.
Causal factors may not only interact as explained above, but they 
can also inﬂ  uence the content of the illness, its ‘colouring’ , and 
its form. This modelling function is described by the term ‘patho-
plastic’ which was introduced by Birnbaum.(27) Pathoplastic features 
are to be distinguished from the more fundamental causes of 
psychiatric illness, but they do exert a predisposing tendency as 
well as a modelling role.
Sociocultural causes
(a) The cult of thinness

The pathoplastic sociocultural causes of eating disorders have been 
subsumed under the term ‘the modern cult of thinness’ prevalent 
in westernized societies.(15) Vulnerable patients are likely to respond 
to this pressure by experimenting with weight-reducing diets which 
carry a degree of risk, and anorexia nervosa is arguably but an 
extension of determined dieting.(28)
It is proposed that the cult of thinness is responsible for the 
increase in the incidence of eating disorders since the 1950s. The 
social pressures which lead to dietary restraint include the publica-
tion of books and magazines advising weight-reducing diets, 
the fashion industry which caters mainly for the slimmer ﬁ  gure, 
television attaching sexual allure and professional success to the

television attaching sexual allure and professional success to the 
possession of a svelte ﬁ  gure, and the emphasis on physical ﬁ  tness 
and athleticism.(3)(b) Changes in the psychopathology of anorexia nervosa
At the beginning of this chapter it was pointed out that the psycho-
logical content and the form of anorexia nervosa have changed 
over historical time and in response to sociocultural inﬂ  uences. 
Whereas Gull and Lasègue spoke only of ‘anorexia nervosa’ and 
‘anorexie hystérique’ respectively, more recent descriptions of the 
psychopathology of anorexia nervosa have stressed a disturbed 
experience of one’s own body,(5) a weight ‘phobia’ ,(29) or a morbid 
dread of fatness.(6) It is precisely the modern anorectic’s dread of 
fatness that is most in keeping with today’s cult of thinness. It is

fatness that is most in keeping with today’s cult of thinness. It is 
arguable therefore that modern societal pressures have determined 
the patients’ preoccupations and contributed to their food 
avoidance. These beliefs are held obstinately and amount to 
overvalued ideas.
(c) Anorexia nervosa as a culture-bound syndrome
The proposition that anorexia nervosa is a culture-bound syndrome 
has much support.(30,31)  An intense fear of becoming obese is 
as culture bound as the disorder koro (a fear of shrinkage of the 
genitals) in Malaysia and South China.
A culture-bound syndrome may be deﬁ  ned as a collection of 
signs and symptoms which is not to be found universally in human 
populations, but is restricted to a particular culture or group of 
cultures. Implicit is the view that culture factors play an important 
role in the genesis of the symptom cluster . . . (30)

Anorexia nervosa meets these criteria, ﬁ  rst because it is limited 
to westernized or industrialized nations, and secondly because it is 
clear that the psychosocial pressures on women to become thin 
constitute a powerful cultural force leading to anorexia nervosa.
In order to allow for exceptions to the rule, when anorexia nervosa 
occurs in non-westernized countries, the illness may be understood 
as arising from cultures undergoing rapid cultural change.(31)
Anorexia nervosa is thus a ‘culture-change syndrome’ , explaining 
its increased incidence in Japan and Israel. Anorexia nervosa 
remains rare in Asia (particularly India), the Middle East (with the 
exception of Israel), and generally in poorly developed countries.
Y oung female immigrants who move to a new culture may suffer

Y oung female immigrants who move to a new culture may suffer 
from an increased prevalence of eating disorders. For example, 
children with anorexia nervosa were found among Asian families 
living in Britain. This was linked with an exposure to a conﬂ  icting 
set of sociocultural norms in comparison with their parents and 
grandparents.(32)
Adverse life events
Anorexia nervosa may be precipitated by adverse life events. Early 
clinical studies depended solely on the patient’s reports of an 
adverse life event preceding the onset of the illness. These varied 
widely in severity and included the death of grandparents, a father’s 
remarriage, a severe physical illness, stress or failure of school 
examinations, or being teased about being overweight.(21)
Recent studies have relied on more objective measurements of

Recent studies have relied on more objective measurements of 
adverse life events and comparisons with control groups. In one 
such study,(33) life events rated included the death of a close 
relative, a poor relationship with parents, or an unhappy marriage. 
Fairly severe life events and lasting difﬁ  culties were found in the 
majority of patients with a late onset (after 25 years), whereas they 
were only found in a minority of patients with an early onset.
Anorexia nervosa can also be precipitated by sexual experiences 
and conﬂ  icts. In a series of 31 adolescent and young women it was Fig. 4.10.1.1 Diagrammatic illustration of the way that genetic predisposition 
interacts with sociocultural pressures to cause anorexia nervosa.
4.10.1 anorexia nervosa

SECTION 4  clinical syndromes of adult psychiatry 780
observed that in 14 ﬁ  rst sexual intercourse had occurred before 
the illness.(34) Sexual problems were seen by 13 patients as major 
precipitants of their illness; 10 of them had experienced inter-course. The authors concluded that a speciﬁ  c aetiological role of 
sexual factors seemed unlikely, but there might be a direct relation-ship between the onset of eating difﬁ  culties and concurrent sexual 
problems.
In a series of 15 patients, anorexia nervosa developed during 
pregnancy or, more often, during the post-natal period when it was accompanied by depression.
(35) Risk factors included ambivalence 
about motherhood, a large weight gain during the pregnancy, physical complications during pregnancy, post-natal depression, and past psychiatric illness.
Childhood sexual abuse

Since it was reported that a high proportion of patients in a treatment programme for anorexia nervosa gave histories of sexual abuse in childhood, it has been supposed that this trauma would be a contributory causal factor.
(36) It would be better if this history 
could be corroborated, but for obvious reasons it is often difﬁ  cult 
to do so. Hence this subject raises unusual difﬁ  culties in judging 
the reliability of the data. Child sexual abuse is also discussed in the chapter on bulimia nervosa (Chapter 4.10.2).
In a careful study of childhood sexual experiences reported by 
women with anorexia nervosa, the authors classiﬁ  ed the events 
according to the seriousness of the sexual act in childhood andconcentrated on sexual experiences with someone at least 5 years older.

(37) They found surprisingly high rates (about one-third) of 
adverse sexual experiences in women with eating disorders,and, unlike other investigators, they did not ﬁ  nd that the frequency 
of these reports was less in anorexia nervosa than bulimia nervosa. They concluded that it was plausible that childhood sexual contact with an adult may in some cases contribute to a later eatingdisorder.
The complexity of this subject has been increased by a study on 
the relationship between sexual abuse, disordered personality, and eating disorders.
(38) The authors found that 30 per cent of patients 
referred to an eating disorders clinic gave a history of childhood sexual abuse. In addition, they found that 52 per cent of their patients had a personality disorder. A signiﬁ  cantly higher propor-

tion of women with a personality disorder had a history of child-hood sexual abuse, compared with those without a personality dis-order. Surprisingly they still concluded that in patients with eating disorders it was not possible to show a clear causal link between child sexual abuse and personality disorder.
In a review of the subject a number of hypotheses were examined 
on the relationship between childhood sexual abuse and eating disorders.
(39) One hypothesis is that child sexual abuse is more 
common in bulimia nervosa than in anorexia nervosa. The authors had to concede that the ﬁ  ndings remain inconclusive. They also 
examined the question of whether child sexual abuse is a speciﬁ  c

examined the question of whether child sexual abuse is a speciﬁ  c 
risk factor for eating disorders. They concluded that this was not the case, as the rates of child sexual abuse in eating disorder patients were similar to or less than those in various other psychiatric com-parison groups. Finally, they found strong evidence that patients with eating disorders reporting child sexual abuse were more likely to show general psychiatric symptoms including depression, alcohol problems, or suicidal gestures, as well as an association with personality disorders.Family factors
Two influential groups of family therapists (Minuchin at the Philadelphia Child Guidance Clinic and Selvini Palazzoli in Milan) have devised family models to explain the genesis of anorexia nervosa.
Minuchin et al. identiﬁ  ed faulty patterns of interaction between

Minuchin et al. identiﬁ  ed faulty patterns of interaction between 
members of the anorexic patient’s family; they in turn were thought to lead to the child’s attempt to solve the family problems by starv-ing herself:
(40) ‘The sick child plays an important role in the family’s 
pattern of conﬂ  ict avoidance, and this role is an important source 
of reinforcement for his symptoms’ . Five main characteristics of family interaction were identiﬁ  ed as detrimental to the function 
of the family: enmeshment (a tight web of family relationships with the members appearing to read each other’s minds), overpro-tectiveness, rigidity, involvement of the sick child in parental con-ﬂ icts, lack of resolution of conﬂ  icts.
Selvini Palazzoli
(41) also identiﬁ  ed abnormal patterns of com-

munication within these families and in addition described abnor-mal relationships between the family members. She assumed that anorexia nervosa amounted to a logical adjustment to an illogical interpersonal system.
Bruch
(42) described girls who developed anorexia nervosa as 
‘good girls’ , who previously had a profound desire to please their families to the point of becoming unaware of their own needs. The frequency of broken families in anorexia nervosa is thought to be fairly low. Anorexic families have been found to be closer: the patients more often perceived themselves as having happy relation-ships within the family.
It remains uncertain whether these abnormal interactions are to 
blame for the illness or develop as a response by parents faced with a starving child. Careful therapists take pains to reassure parents at the commencement of family therapy: ‘ . . . we always ﬁ  nd it useful

to spend some time discussing the nature of the illness, stressing in particular that we do not see the family as the origin of the problem’ .
(43)
A sizeable proportion of patients (30 per cent(15) and 32 per cent(21))
were said to have had a ‘normal’ personality during childhood before their illness. Nevertheless there is general agreement of a close rela-tionship between obsessional personalities and the later develop-ment of anorexia nervosa. In fact Janet, who carefully described obsessions and psychasthenia, was dubious about the validity of the diagnostic concept of anorexia nervosa. He thought that the patient’s fear of fatness was an elaborate obsessional idea.
(44)
In a study of patients admitted for treatment they were classiﬁ  ed 
into anorexia nervosa, bulimia nervosa, or a combination of the two disorders.
(45) Personality disorders were identiﬁ  ed through the

(45) Personality disorders were identiﬁ  ed through the 
Structured Clinical Interview for DSM-IIIR personality disorders (SCID-II). Seventy-two per cent of the patients met the criteria for at least one personality disorder. Anorectics were found to have a high rate of obsessive–compulsive personality disorder.
There have been attempts to disentangle the features of premor-
bid personality and illness in order to clarify the personality characteristics predisposing to anorexia nervosa. Women who had recovered from restricting anorexia nervosa were tested at an 8- to 10-year follow-up, using a number of self-report instruments.
(46)
They were compared with two control groups: normal women and the sisters of the recovered anorexic patients. The women who had

781
recovered rated higher on risk avoidance and conforming to 
authority. They also showed a greater degree of self-control and impulse control, and less enterprise and spontaneity.
Biomedical factors and pathogenesis
(a) Historical notes
Since the early part of the twentieth century a recurring theme has been the possibility that anorexia nervosa is primarily caused by an endocrine or cerebral disturbance. From 1916 there was much preoccupation with the concept of Simmonds’ cachexia,
(47)
the assumed result of latent disease of the pituitary gland. There was diagnostic confusion between anorexia nervosa andhypopituitarism, which was only clariﬁ  ed much later when it 
became known that in true hypopituitarism weight loss andemaciation are uncommon. Hormonal deficits indicative of impaired pituitary function are indeed common in anorexianervosa, but are merely a secondary manifestation of prolonged malnutrition.
Interest in the neuroendocrinology of anorexia nervosa led

Interest in the neuroendocrinology of anorexia nervosa led 
to the formulation of the hypothalamic model.
(6,48)  From the 
beginning the model was aimed at explaining pathogenesis rather than aetiology; it was not considered an alternative to the psycho-logical origin for anorexia nervosa, but a means of explaining a constellation of disturbed neural mechanisms, as follows:
1 a disordered regulation of food intake;2 a neuroendocrine disorder affecting mainly the hypothalamic-
anterior pituitary-gonadal axis;
3 a disturbance in the regulation of body temperature.
It was known that these functions all reside within the complex 
of hypothalamic physiology. A ‘feeding centre’ had been described in the lateral hypothalamus because bilateral lesions there induced self-starvation and death in rats.
(49) Over the years it has become

(49) Over the years it has become 
clearer that many of the disturbances could be attributed to the patients’ malnutrition, as demonstrated by experimental studies in healthy young women who were asked to follow a weight-reducing diet. It was found that ovarian function is extremely sensitive to even small restrictions of caloric intake which often lead to impaired menstrual function.
(50)
(b) Cerebral lesions and disturbances
Interest in the hypothalamic model was fuelled early on by clinical reports of patients diagnosed as suffering from anorexia nervosa who were later found to have cerebral lesions, especially tumours of the hypothalamus. More recently, occult intracranial tumours have been detected, masquerading as anorexia nervosa in young chil-dren.
(51)
Neuroimaging studies in anorexia nervosa have led to ﬁ  ndings sug-
gestive of an atrophy of the brain. CT has disclosed a widening of the 
cerebral sulci and less frequently an enlargement of the ventricles.(52)

The outer cerebrospinal ﬂ  uid spaces were enlarged markedly in 36 per 
cent of the patients. When the CT examination was repeated after 
weight gain 3 months later, the widening of the sulci had disappeared 
in 42 per cent of the patients who had previously shown this ﬁ  nding. 
In other patients, however, the widening remained unaltered for 1 year after body weight had returned to normal.
Functional neuroimaging techniques have also been applied to 
research in anorexia nervosa. Regional cerebral blood ﬂ  ow was measured in three series of children.
(53) In the majority of the chil-
dren there was an above-critical difference in the regional cerebral blood ﬂ  ow most often between the temporal lobes but sometimes

dren there was an above-critical difference in the regional cerebral blood ﬂ  ow most often between the temporal lobes but sometimes 
affecting other brain regions. Hypoperfusion was found on the left side in about two-thirds of the children. Follow-up scans were undertaken in children after they had returned to normal weight; the reduced regional cerebral blood ﬂ  ow in the temporal lobe per-
sisted on the same side as the initial scan. The authors found that there was a signiﬁ  cant association between reduced blood ﬂ  ow and 
impaired visuospatial ability, impaired complex visual memory, and enhanced information processing.
(c) Genetic causes
As with general psychiatric disorders, genetic and environmental factors are no longer viewed as opposing causes of anorexia nervosa, but rather as interacting with one another. Thus there may be groups of genes that determine risk of the illness and speciﬁ  c

environmental situations that elicit or prevent the expression of these genes. There is evidence for a family aggregation of anorexia nervosa. This does not necessarily mean that the origin of the disorder is genetic because environmental factors common to the family must also be considered. In a series of 387 ﬁ  rst-degree 
relatives of 97 probands with anorexia nervosa, it was found that the illness occurred in 4.1 per cent of the ﬁ  rst-degree relatives of 
the anorexic probands, whereas no case was found among relatives of the controls who were probands with a primary major affective disorder, or with various non-affective disorders.
(54) The authors 
concluded that anorexia nervosa was familial with intergeneration-al transmission. It was roughly eight times more common in female ﬁ rst-degree relatives of anorexic probands than in the general 
population. The absence in the relatives of probands with major affective disorder indicated the speciﬁ  city in the risk of transmis-

sion of anorexia nervosa and the absence of shared familial liability with affective disorders.
The strongest argument favouring a part-genetic causation of 
anorexia nervosa is derived from the classical method of comparing the concordance rate of the illness in monozygotic and dyzygotic twins. Underlying the method of twin studies is the supposition that the environment for MZ twins and DZ twins is the same, or at least it does not differ in such a way as to cause greater concordance 
for MZ twins. Although it is known that the environments shared 
by MZ twins are more often similar than those shared by DZ twins, these similarities are thought not to be of aetiological relevance to anorexia nervosa.
(55) The ﬁ  rst sizeable series of twins came from

(55) The ﬁ  rst sizeable series of twins came from 
the Maudsley Hospital and St George’s Hospital in London and showed higher concordance rate for MZ than for DZ twins.
(56)
Since then the ﬁ  ndings have been replicated and the analysis of the 
twin data has suggested that the liability can be broken down into three sources of variability:
a
2 Additive genetic effects 88 per cent
c2 Common environmental effects, found to be 0
e2 Individual-speciﬁ  c environmental effects.(55) 12 per cent
The individual-speciﬁ  c environmental effects are those which 
contribute to differences between the members of the twin pair. This would happen if only one member of the twin pair had suffered from an adverse effect. It is perhaps surprising that the unique environmental effects contribute to the disorder but not the twins’ common environment.4.10.1 anorexia nervosa

SECTION 4  clinical syndromes of adult psychiatry 782
Bulik has found the concept of heritability and its estimation 
prone to misinterpretation. There is not just one heritability esti-mate because this statistic varies across the population sampled and the time of the study. One estimate of heritability of anorexia nervosa gave it as 0.74 in 17-year-old female twins.
(55)
It remains uncertain how the genetic vulnerability to anorexia 
nervosa expresses itself in terms of the pathogenesis of this disor-der. One view is that this vulnerability confers instability of the homeostatic mechanisms, which normally ensure the restoration of weight after a period of weight loss. This hypothesis would explain why in western societies, where dieting behaviour is common, those who are genetically vulnerable would be more likely to develop anorexia nervosa.
(57) It has also been found that MZ 
twins have a higher correlation for the trait of ‘body dissatisfaction’ than DZ twins.
(55)

(55)
(d) Neurotransmitters
Since the early 1970s, the hypothalamic model of anorexia nervosa has been transformed from a consideration of anatomical ‘centres’ to ‘systems’ involving neurotransmitters. Much evidence has been presented to show that a wide range of neurotransmitters modulate feeding behaviour, and it was only a small conceptual step to sug-gest that some were involved in the pathophysiology of eating dis-orders. At ﬁ  rst the neurotransmitters considered were mainly the 
monoamine systems-noradrenaline (norepinephrine), dopamine, and serotonin. In addition, opioids, the peptide chole-cystokinin, and the hormones corticotrophin-releasing factor and vasopressin have also been thought to play a part in the pathogen-esis of eating disorders. During recent years the main interest has been focused on the role of serotonin (5-hydroxytryptamine,

5-HT) in the control of natural appetite, especially those aspects concerning the phenomenon of satiety, mediated through a range 
of processes called the ‘satiety cascade’ .
(58) There is now strong 
evidence that pharmacological activation of serotonin leads to an inhibition of food consumption. It was also postulated that a defect in serotonin metabolism confers a vulnerability to the development of an eating disorder.
(59)
A boost to the concept of altered serotonin activity in anorexia 
nervosa has come from research showing that these patients while still underweight had signiﬁ  cant reductions in cerebrospinal ﬂ  uid 
5-hydroxyindoleacetic acid ( 5-HIAA ). The levels became normal 
when the patients were retested 2 months after they reached their target weight.
(60) In order to test whether these ﬁ  ndings were

(60) In order to test whether these ﬁ  ndings were 
secondary to malnutrition, the researchers resorted to the inge-nious step of studying patients after ‘recovery’ when they had reached normal weight. They found elevated levels of cerebrospinal ﬂ uid 5-HIAA, possibly indicating increased serotonin activity 
contributing to the abnormal eating behaviour which often persists in patients who have otherwise recovered.
(61) The arguments 
against this simple model of enhanced serotonin activity as a vulnerability trait in anorexia nervosa should be brieﬂ  y presented. 
Serotonin function was again assessed in long-term weight-restored anorectics.
(62) The investigators used a dynamic neuroendocrine 
challenge with d-fenﬂ  uramine as a speciﬁ  c probe of serotonin

challenge with d-fenﬂ  uramine as a speciﬁ  c probe of serotonin 
function, which mediates the release of prolactin. If there were any persistent abnormality in serotonin function, the response to this challenge test should differ from that in normal controls. In fact, the rise in prolactin levels was very similar in former patients and normal controls. Accordingly, this study failed to support the notion of increased central serotonin function as a vulnerability 
trait in anorexia nervosa.
(62)
Clinical features: classical anorexia nervosa 
(postpubertal)
The illness usually occurs in girls within a few years of the menarche 
so that the most common age of onset is between 14 and 18. Sometimes the onset is later in a woman who has married and had children.
By the time the patient has been referred for psychiatric treat-

ment she is likely to have reduced her food intake and lost weight over the course of several months, and her menstrual periods will have ceased. A regular feature of the illness is its concealment and the avoidance of treatment. Even after having lost 5 to 10 kg in weight and missed several periods, the patient’s opening remark is often ‘there is nothing wrong with me, my parents are unduly worried’ . It is only when the clinician asks direct questions that she will admit to insomnia, irritability, sensitivity to cold, and a with-drawal from contacts with her friends, including her boyfriend if she has one.
Because of this denial, it is important to enquire from a close 
relative, as well as the patient, about the most relevant behavioural changes.
History

History
History of food intake.  A food intake history  is obtained by ask-
ing the patient to recall what she has eaten on the previous day, commencing with breakfast, which is often missed. An avoidance of carbohydrate and fat-containing foods is the rule. What remains is an often stereotyped selection of vegetables and fruit. ‘Diet’ drinks and unsweetened fruit juice are preferred, although some patients are partial to black coffee. It is the mother who will indi-cate that her daughter ﬁ  nds ways of avoiding meals, preferring to 
prepare her own food and withdrawing into her bedroom to eat it.
W eight history.  The patient is usually willing to provide an 
accurate weight history . She may try to conceal her optimum

accurate weight history . She may try to conceal her optimum 
weight before her decision to ‘diet’ , but she is likely to be objective about her current weight, if only to express pride in the degree of ‘self-control’ she has exerted. The clinician then has an opportunity to enquire into her ‘desired’ weight by simply asking what weight she would be willing to return to. Her answer will betray a determi-nation to maintain a suboptimal weight.
History of exercising.  A history of exercising  should be taken.

History of exercising.  A history of exercising  should be taken. 
Again, the patient is likely to conceal the fact that she walks long distances to school or to work rather than use public transport. She may also cycle vigorously or attend aerobic classes. A parent may report that his or her daughter is running on the spot or perform-ing press-ups in the privacy of her bedroom, judging from the noise that can be heard. The amount of exercising may be grossly exces-sive, with the patient indulging in brisk walks or jogging even in the presence of painful knees or ankles due to soft tissue 
injuries.
Additional harmful behaviours,  which should be enquired into 
include self-induced vomiting, purgative abuse, and self-injury. Vomiting and purgative abuse are similar to the behaviours that occur in bulimia nervosa (see Chapter 4.10.2). In anorexia

783
nervosa they may occur without the prelude of overeating and the 
patient’s motive is simply to accelerate weight loss. The laxative abuse is often at the end of the day. The favourite laxatives in the United Kingdom are Senokot and Dulcolax, and the patient is likely to take them in increasing quantities to achieve the wanted effect as tolerance develops. Self-injury should also be enquired into, and the skin of the wrists and forearms inspected for scratches or cuts with sharp instruments.
Menstrual history.  The patient may not volunteer that her 
periods ceased soon after commencing the weight-reducingdiet. On the other hand she may admit that she is relieved thather periods have stopped as she found them to be a nuisance or unpleasant.
(a) The patient’s mental state
(i) Speciﬁ  c psychopathology
Several near-synonyms have been used to describe the speciﬁ  c 
attitude detectable in the patient who systematically avoids fatness: a ‘disturbance of body image’ ,

(5) a ‘weight phobia’ ,(29) or a ‘fear of 
fatness’ .(6) Magersucht, or seeking after thinness, was a term applied 
in the older German literature. The patient will express a sensitivity about certain parts of her body, especially her stomach, thighs, and hips. Not only is she likely to assert that fatness makes her unat-tractive, but she may add that it is a shameful condition betraying greed and social failure. These distorted attitudes generally amount to overvalued ideas rather than delusions. Occasionally, however, a patient may be frankly deluded, such as one young woman who believed that her low weight was due to thin bones and that fatness was still evident on the surface of her body.
Studies have demonstrated that wasted patients, when asked

Studies have demonstrated that wasted patients, when asked 
to estimate their body size, see themselves as wider and fatter than they actually are.
(63) Since these early observations, numerous 
perceptual studies have been undertaken and the conclusion drawn that anorexic patients overestimate their body width more often than normal controls. These distorted attitudes are often associated with a negative affect, so that the disturbance might be viewed as one of ‘body disparagement’ .
(64)
The patient’s dread of fatness is so common that it is pathogno-

(64)
monic of anorexia nervosa. There are, however, exceptions. Sometimes a patient may simply deny these faulty attitudes. Another exception is the occurrence of anorexia nervosa in eastern countries where thinness is not generally admired (e.g. Hong Kong and India). The imposition of fear of fatness as a diagnostic crite-rion on patients from a different culture, where slimness is not valued, amounts to a failure to understand the illness in the context of its culture.
(65) An appropriate solution, proposed by Blake 
Woodside(66) is to accept diagnostic criteria where the psychopa-
thology includes culture-speciﬁ  c symptoms which will differ for 
western, Chinese, and Indian ethnic groups.
(ii) Denial
Denial in anorexia nervosa is sometimes included within diagnos-tic criteria of the disorder, for example DSM-IV . Vandereycken
(67)

(67)
has written a scholarly treatize on the subject. He has pointed out that the term ‘denial’ is used with apparently simplicity in clinical practice, but this stands in contrast to its intriguing complexity. It is a multi-layered concept, which is difﬁ  cult to measure. Denial is 
not a static condition but ﬂ  uctuates over time. A crucial element in 
its assessment is the inherent conﬂ  ict of perception between the patient and the clinician. The patient carries out distortions by 
omissions, concealments, or misrepresentations. She often denies hunger and fatigue and appears not to accept that she is thin. She shows a lack of concern for the physical and psychosocial sequelae of being underweight and may even deny the danger of her condition.
Vandereycken has proposed two categories of denial:

1 Unintentional denial (e.g. the patient’s way to improve her 
self-esteem and preserve her sense of identity).
2 A deliberate denial including the pretence of being healthy and 
avoiding the treatment others want her to accept. Strong denial is often accompanied by the avoidance of treatment, but the refusal of help is not entirely due to the patient’s lack of recognition of her problems.
(iii) Depression
Depression of varying severity, including a major depressivedisorder, is common. The patients express guilt after eating, add-ing that they do not deserve food. A high rate of depression(42 per cent) was found at presentation in one study
(21) and the 
lifetime history of depression in follow-up studies may be as high as 68 per cent.
(iv) Obsessive–compulsive features
The patients frequently eat in a ritualistic way, for example restrict-
ing their food intake to a narrow range of foods which experience

ing their food intake to a narrow range of foods which experience 
tells them are ‘safe’ because they will not lead to weight gain. There is often a compulsive need to count the daily caloric intake. One 
patient rejected prescribed vitamin tablets in case they contained ‘calories’ . The frequency of obsessive–compulsive disorder in anorexia nervosa was found to be 22 per cent in a clinical series.
(21)
In studies using structured clinical interviews the frequency ranged from 25 to 70 per cent.
(v) Neuropsychological deﬁ  cits
These deﬁ  cits are seldom detected clinically, and an emaciated 
patient may pursue studies and obtain surprisingly good examina-tion marks. On the other hand, neuropsychological testing has revealed deﬁ  cits in attention, and impairment of memory and 
visuospatial function.
(59)
(b) The endocrine disorder

(59)
(i) The impairment of hypothalamic-pituitary-gonadal function
Amenorrhoea is an early symptom of anorexia nervosa and in a 
minority of patients may even precede the onset of weight loss. Amenorrhoea is an almost necessary criterion for the diagnosis of 
anorexia nervosa. An exception is when a patient takes a contracep-tive pill, which replaces the hormonal deﬁ  cit and may lead her to 
say she still has her periods.
Generally, when the patient is undernourished, levels of gonado-
trophins and oestrogens in the blood are found to be low or undetectable. Not only do malnourished patients show low blood 
levels of luteinizing hormone and follicle-stimulating hormone, 
but the secretion patterns of these pituitary hormones regress to a 
phase of earlier development. For example, severely wasted patients 
display an infantile luteinizing hormone secretory pattern with 
a lack of major ﬂ  uctuations over the course of 24 h. With some

a lack of major ﬂ  uctuations over the course of 24 h. With some 
degree of weight gain a pubertal secretory pattern appears, consist-ing ﬁ  rst of a sleep-dependent increase of luteinizing hormone
at night, and later displaying more frequent fluctuations.
(68)4.10.1 anorexia nervosa

SECTION 4  clinical syndromes of adult psychiatry 784
When a patient is still malnourished the ultrasound pelvic exami-
nation will reveal that ovarian volume is much smaller than innormal women.
(69) Three stages can be discerned in the appear-
ance of the ovaries as the patient gains weight:
1 small amorphous ovaries;
2 multifollicular ovaries (with cysts 3–9 mm in diameter);3 dominant follicle (10 mm or more in diameter).
At the same time there is a corresponding return of hormonal 
secretion; follicle-stimulating hormone appears ﬁ  rst, followed by 
luteinizing hormone and ﬁ  nally oestradiol which leads to enlarge-
ment of the uterus.
(70)
These abnormalities signify that the patient is infertile and 
remains so until endocrine function recovers. Pregnancy occasion-ally occurs as the patient is still underweight and improving but before the appearance of the first menstrual period.
(71)
The pregnancy carries a risk of poor foetal growth during the ﬁ  rst

(71)
The pregnancy carries a risk of poor foetal growth during the ﬁ  rst 
trimester, albeit with some ‘catch-up’ growth during the neonatal period.
(72) Occasionally an underweight anorexic patient may seek 
treatment at an infertility clinic. Treatment with gonadotrophin-releasing hormone may restore fertility, but this practice has been severely criticized.
(73)
(ii)  Hypothalamic-pituitary-adrenal and hypothalamic-
pituitary-thyroid axes
The emaciated anorexic patient shows an increased 24-h plasma 
cortisol level which returns to normal with a minimal increase in weight, as it is the nutritional intake that is critical.
(74)
Reduced tri-iodothyronine (T3) levels are linked to a reduction 
in energy expenditure during starvation and are adaptive in nature, so that treatment with L-thyroxin is not appropriate in anorexia nervosa.
(68)
(c) Weight loss and malnutrition
(i) Body weight
The severity of weight loss may be recorded as follows:

(68)
1 As a percentage of an ‘average’ body weight to be found in tables 
for normal populations according to age and height (e.g. the Metropolitan Life Insurance Tables ).
2 As a percentage drop from the patient’s ‘healthy’ weight before 
the onset of her illness.
3 Using the Quetelet body mass index
BMI =  weight (kg)
(height (m))
2
A BMI between 20 and 25 is regarded as healthy. A BMI of 14 
or less indicates a need for hospitalization. A BMI between 10 and 12 represents the lower limit of human survival.
(ii) Physical examination
Wasting is variable but may be extremely severe, resulting in a skull-like appearance of the head, stick-like limbs, and ﬂ  at breasts,

Wasting is variable but may be extremely severe, resulting in a skull-like appearance of the head, stick-like limbs, and ﬂ  at breasts, 
buttocks, and abdomen. The hands and feet feel cold and readily turn blue in winter. The skin is dry with an excess of downy hair (lanugo) covering the cheeks, the nape of the neck, the forearms, and the legs. Heartbeat is slow (50–60 beats/min) and the blood pressure is low (e.g. 90/60 mmHg) with orthostatic lability. During the routine physical examination muscle power should be tested to detect proximal myopathy, as explained below.Differential diagnosis of classical anorexia nervosa
The diagnosis of anorexia nervosa is usually straightforward, especially as the modern diagnostic criteria are objective. Wasting diseases such as inﬂ  ammatory bowel disease (Crohn’s disease or 
ulcerative colitis), thyrotoxicosis, and diabetes mellitus may some-times be mistaken for anorexia nervosa, but they can be identiﬁ  ed

ulcerative colitis), thyrotoxicosis, and diabetes mellitus may some-times be mistaken for anorexia nervosa, but they can be identiﬁ  ed 
through speciﬁ  c investigations. Occasionally there is an interaction 
between such a medical illness and anorexia nervosa, when a patient wishes to perpetuate the weight loss caused by the former. 
Rarely, anorexia nervosa may be mimicked by a cerebral tumour 
altering the function of the hypothalamus.
In older patients there may be diagnostic difﬁ  culty with a major 
depressive or schizophrenic illness. The weight loss in a severe depressive illness results from loss of appetite and the patient’s belief that she does not deserve food. A schizophrenic patient may avoid food because of paranoid delusions of being poisoned.
Complications of malnutrition

The complications, which are part of the illness, such as amenor-rhoea due to failure of the hypothalamic-pituitary-gonadal axis, have already been discussed. The range of medical complications has been extensively reviewed,
(74) with recommendations for the 
investigations needed on presentation of the patient.
(a)  Fluid and electrolyte disturbances and cardiovascular 
complications
Patients who induce vomiting, abuse laxatives, or take diuretics are 
likely to experience dehydration and various electrolyte distur-bances.
(i) Self-induced vomiting
Loss of gastric acid leads to a metabolic alkalosis and hypokalaemia. A low serum level of potassium may lead to cardiac conduction defects and arrhythmias, skeletal muscle weakness, and renal tubu lar 
dysfunction.
(ii) Laxative abuse
The abuse of laxatives is likely to cause dehydration, metabolic acidosis, hyponatraemia, and hypokalaemia.
(iii) The use of diuretics

The use of diuretics such as the thiazide group gives rise to low serum sodium levels which in turn cause fatigue and general weak-ness. A level below 120 mmol/l may lead to coma. The patient often justiﬁ  es the use of a diuretic as a treatment for swollen ankles or 
even ‘bloating’ of the stomach, which she misinterprets as being due to ﬂ  uid retention.
(iv) Impaired renal function
This may be caused by different mechanisms: pre-renal failure due 
to dehydration or hypokalaemic nephropathy.
(b) Peripheral oedema
Fluid retention leading to oedema occurs frequently in patients with anorexia nervosa. It is important to distinguish between ‘benign’ oede-ma, which often occurs during the course of effective refeeding, and oedema from other causes, which may have serious consequences.
(i) ‘Benign’ oedema

‘Benign’ oedema may occur during inpatient treatment. If the patient accepts a high-caloric intake, ﬂ  uid retention is the rule as 
shown by a steep upward rise in the weight curve.

785
(ii) Famine oedema
If oedema is detected when the patient ﬁ  rst presents clinically, or if 
it develops without a preceding improvement in food intake, the underlying mechanisms should be carefully investigated in order to avoid the risks of congestive cardiac failure and pulmonary oedema. By the time peripheral oedema is detectable, the amount of ﬂ uid retained in the body contributes several kilograms to the 
patient’s weight, thereby concealing the true loss of weight. It is a misconception that peripheral oedema is usually due to a lowering of plasma albumen, as this is not necessarily so in anorexia nervosa. Therefore the clinician must look for other reasons.
1 A fall in interstitial ﬂ  uid pressure has been proposed whereby 
water seeps from the blood into the interstitial spaces
(75) whereas 
the total exchangeable sodium is likely to remain within the normal range.
2 ‘Rebound’ oedema following hyponatraemia due to abuse of 
laxatives or diuretics.

3 Wet beri–beri: vitamin deﬁ  ciency in anorexia nervosa is uncom-
mon because many patients continue to eat vegetables and fruit. Nevertheless a lack of vitamin B
1 (thiamine) may occur in 
patients who eat a stereotyped diet, and Wernicke’s encephalopa-thy may follow.
(76) It may also lead to congestive cardiac failure 
with severe oedema from a nutritional cardiomyopathy, precipi-tated by refeeding without thiamine.
4 Congestive heart failure and pulmonary oedema may occur as 
a result of general undernutrition leading to a decreased cardiac mass, cardiac output, and volume. Death may be caused by an 
injudicious intravenous infusion of ﬂ  uids .
(c) Metabolic disturbances
(i) Hypoglycaemia
Severe hypoglycaemia with plasma glucose levels as low as

Severe hypoglycaemia with plasma glucose levels as low as 
1.0 mmol/l is recognized as a cause of death. Hypoglycaemia may go unrecognized, as a lack of sympathetic nervous response may mask the classical symptoms and signs.
(ii) Hypercarotenaemia
This is a benign condition causing an orange–yellow colouration of the skin of the palms, soles, forearms, and the region of the nose. It is partly due to the consumption of large amounts of foods rich in carotenoids, especially carrots, tomatoes, and the green outer leaves of vegetables.
(d) Myopathy
Weakness of speciﬁ  c muscle groups is common and is due to severe 
protein-energy malnutrition. There is a ‘proximal’ myopathy, affect-ing the musculature of the pelvic girdle and the shoulder girdle. The patient ﬁ  rst notices an increasing difﬁ  culty in climbing stairs.

Weakness may also affect the muscles of the head and neck and the face. When the patient is asked to rise from a sitting position, she will tend to push herself up using her hands and arms. She also has difﬁ  culty in rising unaided from a squatting position.
(78)
There are no characteristic abnormalities in blood chemistry, 
although creatine kinase and liver enzymes may be elevated and the activity of the enzyme carnosinase may be reduced. Myopathic changes are consistently present in muscle biopsy specimens. Histology reveals the ‘chequerboard’ distribution of muscle ﬁ  bres 
with a selective type 2 ﬁ  bre atrophy. Electron microscopy reveals the presence of strikingly abundant glycogen granules between the 
myoﬁ  brils and under the sarcolemma.
(78)
The detection of myopathy is a clear indication for the patient’s 
admission to hospital and a refeeding programme. After a weight gain of a few kilograms her muscle strength will begin to return and a complete recovery is the rule.

(e) Osteoporosis
A high proportion of patients with anorexia nervosa risk develop-ing osteoporosis and consequent pathological fractures. Signiﬁ  cant 
reduction in bone mineral density of the femoral neck was found in all 20 patients with anorexia nervosa of 6 years or more dura-tion.
(79) The favourite method of measuring bone density in the 
lumbar spine and hip is by dual-energy X-ray absorptiometry. A measurement for all patients with anorexia nervosa of 2 years duration or more is recommended.
(74, 79) It is difﬁ  cult to disentan-
gle the harmful effect of the nutritional deﬁ  ciency itself from the 
associated oestrogen deﬁ  ciency. The pathogenesis of osteoporosis 
in anorexia nervosa differs from that in postmenopausal women. In anorexia nervosa the nutritional deﬁ  ciency (including a lack

in anorexia nervosa differs from that in postmenopausal women. In anorexia nervosa the nutritional deﬁ  ciency (including a lack 
of calcium and vitamin D) leads to a low rate of the recycling of bone through bone formation and resorption, but the balance is disturbed with a relative increase in bone resorption.
The evidence favours the likelihood of improvement of bone 
density with nutritional recovery and resumption of menstrua-tion.
(79) There is much uncertainty about the best treatment. 
Although patients are often automatically prescribed oestrogen replacement, the only controlled trial undertaken so far indicated that oestrogen was only effective in severely underweight anorexic patients.
(81) Indeed, it has been argued that oestrogen replacement 
could be harmful in some patients (children with premenarchal onset) and unnecessary in others with an illness of less than 3 years duration.

(82) Instead the emphasis should be on encouraging 
weight gain, with the possible addition of calcium and vitamin D. Older patients with a poor prognosis (e.g. who have been ill over 10 years) might beneﬁ  t from oestrogen replacement. There is little 
evidence for the use of other medication such as biphosphonates.
(f) Disturbed temperature regulation

Disturbances in the control of temperature are evident from clinical observations; the patients frequently complain of feeling cold, and in the winter they have cold and blue extremities and suffer from chilblains. In the severely malnourished patient hypo-thermia may be a cause of death. Severe malnutrition is accompa-nied by a low central body temperature, presumably because of a low metabolic rate. Ingestion of a high-calorie meal can cause a signiﬁ  cant increase in the central body temperature
(83) with com-
plaints of heat in the periphery and sweating after food.
(g) Haematological changes
Anorexic patients may develop a signiﬁ  cantly lowered haemoglo-
bin level and a reduced haematocrit and white cell count, with a relative decrease in neutrophil leucocytes and an increase in lym-phocytes.
(84) The anaemia is usually moderate and is normocytic

(84) The anaemia is usually moderate and is normocytic 
normochromic in type. The mechanism is that of starvation-induced bone marrow hypoplasia. Only occasionally is there an iron deﬁ  ciency. The anaemia gradually becomes corrected with 
weight gain. A low platelet count in the blood has also been observed and there may be an associated thrombocytopenic purpura.4.10.1 anorexia nervosa

SECTION 4  clinical syndromes of adult psychiatry 786
(h) Complications arising during rapid refeeding
(i) Acute dilatation of the stomach
This complication has been described in anorexia nervosa during 
the course of refeeding.(85) The patient develops copious vomiting, 
upper abdominal pain, distension of the upper abdomen, and rapid dehydration. Treatment is by continuous gastric aspiration, and this complication is one of the rare indications for intravenous infusions of glucose and saline. Gastric dilation is best prevented by avoiding a food intake above 1500 cal daily during the ﬁ  rst week 
of refeeding.
(ii) Hypophosphataemia
When the illness has been protracted and has led to severeemaciation, the body stores of phosphate become depleted. The fall in serum phosphate is aggravated during refeeding, especially parenteral feeding.
(86) Levels of phosphate may fall as low as

0.2 mmol/l. Clinical features are cardiac irregularities with a pro-longed QT interval, impairment of consciousness, and delirium. Treatment is with oral phosphates rather than by intravenous administration.
Anorexic mothers as parents
A patient who is improving may conceive despite having a subopti-mal weight and still not menstruating.
(71) A mother may also 
develop the illness after having borne children. In a series of eight mothers, 9 out of 13 of their children suffered from food depriva-tion, identiﬁ  ed by reductions in weight for age and in height for age 
as shown on Tanner–Whitehouse charts.
(87) The anorexic mothers 
had no intention of abusing the children and indeed were affec-tionate towards them. They simply extended their abnormal 
concern with body size to their own children . They adopted dif-

ferent ways to ration their children’s food intake according to their age. They might prolong breast feeding, dilute the bottle feeds, reduce the amount of food available in the home, conﬁ  ne eating to 
meal times, forbid the consumption of sweets, and prevent others giving them food. An important part of the management is to anticipate the risk to any children and conduct tactful enquiries. A whole-family approach should be adopted, focusing on the chil-dren’s needs for food. The children should be followed up to ensure that they gain weight and catch-up growth is established.
(87)
Clinical features: anorexia nervosa of 
early onset (premenarchal)
It would be too arbitrary to deﬁ  ne an early onset by age limits such

(87)
It would be too arbitrary to deﬁ  ne an early onset by age limits such 
as an onset from 8 to 16 years. A more meaningful frame of refer-ence is the onset in relation to the stage of puberty reached by the child.
(88) Because puberty is a complex developmental process 
spanning 2 to 3 years, it is best to name as ‘premenarchal’ the illness which commences some time after the ﬁ  rst signs of puberty and 
before its completion as shown by the ﬁ  rst menstrual period. 
In true prepubertal anorexia nervosa the illness begins even earlier, before the very ﬁ  rst signs of puberty. Postpubertal anorexia nervosa 
is when the illness commences after menstruation has been established.
There is much similarity between the clinical features of an

There is much similarity between the clinical features of an 
illness of early onset and one which is postpubertal. However, there are two important differences. The ﬁ  rst is the potential for the illness to interfere with the child’s pubertal development. The second 
is the heart-rendering impact on the child’s family. It follows that the management of the family is of supreme importance, and the clinician should be prepared for parental reactions, which may detract from a rational plan of treatment.
The clinical presentation is variable. Often there are precipitating 
events such as a family bereavement or a physical illness leading to weight loss. The onset is likely to be insidious,
(18) with the parents 
noticing nothing amiss except for non-speciﬁ  c features. Symptoms 
of depression and irritability are common.(14,77) Some children

of depression and irritability are common.(14,77) Some children 
cannot describe feelings of depression, but tearfulness may be obvious. They withdraw from friends and may refuse to go to school. Others express ideas of being underserving of love or food. Increasingly these youngsters have been found to injure themselves, especially by scratching with their nails or cutting the skin of the wrists and forearms with sharp objects, and occasionally by knocking and bruising the head. In a severe depression the child may say she hears voices calling her ‘bad’ , but further questioning indicates that these are not true hallucinations but vivid expres-sions of her own thoughts. Another common presentation is with bodily symptoms, especially headaches, abdominal discomfort, and a wide range of gastrointestinal symptoms, which inevitably elicit physical investigations.

At some stage, however, the parents observe that their child is 
avoiding food and is reluctant to eat at normal meal times. She resorts to deviousness and secrecy. The omission of school meals often goes undetected. Eventually it is noticed that she has become thinner and may have lost a great deal of weight. Resistance is met when attempts are made to reverse the loss of weight. Even a young child may become preoccupied with the caloric values of foods and adopt additional methods of inducing weight loss. The child 
is likely to exercise excessively—jogging, walking, or cycling long 
distances. An attempt to reduce the excess activity may lead to soli-tary exercising in the bedroom, including press-ups or running on the spot. Other patients may induce vomiting or take laxatives even after small meals, but overeating typical of bulimia nervosa is rare in young children.
(77)
(a) Weight loss

(77)
Because of the early onset while the child should still be growing in stature, there is a failure to gain the weight, which normally accompanies the growth spurt. Later there occurs an actual loss of weight and, because the child has not yet reached her optimum weight, a very low weight indeed may result—25 kg or even less. Symptoms of malnutrition ensue including tiredness, constipation, and sensitivity to cold with cold extremities.
(b) The psychological disorder
Even younger children are likely to disclose that they are fearful of becoming fat, a disturbance similar to the overvalued idea held by older patients. A minority of patients will disclose their reluctance to develop personal, sexual, or social maturity, in a manner, which ﬁ ts into Crisp’s model (see p. 796 of this chapter). A few may express

reluctance to have menstrual periods. A girl may say she is indif-ferent whether she menstruates or not, but would like to develop breasts like other girls in her class. The reluctance to ‘grow up’ may be expressed in social terms, with the patient saying that she could not imagine herself ever leaving home or her mother. On the other hand most girls are keen to reach a normal stature.

787
Severe depression was found in 69 per cent of youngsters in the 
Göteborg study.(14) In the same series one-third of the patients 
had an obsessive–compulsive personality disorder, and 8 per cent developed hand-washing and other compulsions.
(c) Physical examination
Physical examination will reveal a varying degree of wasting, affecting the limbs, the abdomen, the buttocks, and the facial appearance. The extremities are blue and cold, and ischaemic changes may lead to gangrene affecting the toes. Other physical changes are similar to those in the adult, with the addition of a delay in puberty.
(d) Delay or arrest of puberty
The illness may adversely affect pubertal development depending on its time of onset. If the onset is truly prepubertal the child will not yet have shown the ﬁ  rst signs of puberty, such as the

The illness may adversely affect pubertal development depending on its time of onset. If the onset is truly prepubertal the child will not yet have shown the ﬁ  rst signs of puberty, such as the 
appearance of pubic hair and breast buds. When the illness begins during the course of puberty these early signs may have appeared, but the breasts will show early growth only (Tanner stages 1 or 2), and the child will not yet have menstruated. The effects on pubertal development can be divided into those affecting growth in stature, breast development, and menstrual function.
(88)
(i) Growth in stature
Growth in stature  may have become arrested. In a series of 20 
patients with a premenarchal onset, only two of them had reached the 50th centile in height. With successful treatment and weight gain, catch-up growth of 2 to 5 cm may be achieved, but only in patients aged 17 or less.
(88)
(ii) Breast development
Breast development : in the same series only six patients had nor-

(88)
mal breasts and as many as 10 had infantile breasts. After prolonged weight gain, eight of the 14 patients showed a considerable response in breast growth.
(88)
(iii) Menstrual function
Menstrual function : Primary amenorrhoea is the rule. In the series 
already referred to only four of the 20 patients had menstruated by the age of 16 years. A further three began their periods between 16 and 18 years of age, and four at ages ranging from 18 to 25. The remaining patients had prolonged amenorrhoea.
The above series consisted of selected patients in whom pubertal 
delay was severe, whereas marked pubertal delay has seldom been reported in other series in which only delayed menstruation has been remarked upon.
A young boy who develops anorexia nervosa is also likely to

A young boy who develops anorexia nervosa is also likely to 
become preoccupied with fatness and accordingly avoids food in order to lose weight. The endocrine disorder in the male similarly consists of a disturbance of the hypothalamic-pituitary-gonadal axis. With a prepubertal onset, the penis and scrotum remain 
infantile, there is only a scanty growth of pubic and facial hair, and 
the voice may not break.
Special investigations
Pelvic ultrasound monitoring of the ovaries and uterus is a useful method of ascertaining regression and recovery in children with anorexia nervosa.
(89) On ﬁ  rst testing, and in the presence of low 
weight and amenorrhoea, ovarian volume and uterine volume were found to be reduced in comparison with normal pubertal girls. In the latter the normal range of ovarian volume is 3.95 ± 1.7 cm
3
and uterine volume is 14.8 ± 7.6 cm3. On retesting the patients 
18 months after the ﬁ  rst scan those who were menstruating showed

3
18 months after the ﬁ  rst scan those who were menstruating showed 
signiﬁ  cantly larger ovarian and uterine volumes than those with 
amenorrhoea. The authors concluded that for ovarian and uterine maturity to occur it is necessary to achieve a mean weight of 48 kg 
and a mean weight-to-height ratio of 96.5 per cent. They found that pelvic ultrasound scanning helped to motivate the children to 
accept a higher body weight.
Differential diagnosis of early-onset anorexia nervosa
Frequent bodily complaints, loss of weight, and abnormalities of growth lead these children to be referred to paediatricians for special investigations. It has been proposed that young anorexic boys should be investigated by means of neuroimaging, so as not to miss occult intracranial tumours.
(32) The diagnosis of anorexia 
nervosa should be distinguished from atypical eating disorders in childhood.
(77)

(77)
Pervasive refusal syndrome  is characterized by a child refusing to 
eat, drink, walk, talk, or take care of herself. Anxiety, phobic responses, and depression are also present.
Selective eating  is the term applied to a child who restricts food 
intake to two or three different foods, such as biscuits, crisps, or potatoes, but usually remains in good health.
Food avoidance emotional disorder.  this condition is one in which 
food avoidance is attributable to an emotional disturbance in the absence of a dread of fatness, a necessary criterion for the diagnosis of anorexia nervosa.
Food fads and food refusal.  they are usually intermittent and 
physical health is not compromised.
ICD-10(80) (including patients with premenarchal 
onset(88))
1 Body weight is maintained at least 15 per cent below that expected

1 Body weight is maintained at least 15 per cent below that expected 
for health. Prepubertal children may fail to gain the weight expected during the growth spurt. Weight loss is caused by avoid-ance of ‘fattening’ foods, possibly with the addition of self-induced vomiting, purgative abuse, excessive exercise, or the use of appetite suppressants.
2 The patient holds the overvalued idea of a dread of fatness and 
keeps her weight below a self-imposed threshold.
3 There is an endocrine failure manifest in women as amenorrhoea 
and in men as a loss of sexual interest and potency.
4 If the onset is premenarchal, the sequence of pubertal events is 
delayed: growth is arrested; in girls the breasts do not develop and there is a primary amenorrhoea; in boys the genitals remain juvenile.
DSM-IV(90)
1 Refusal to maintain body weight above the minimally normal

1 Refusal to maintain body weight above the minimally normal 
weight for age and height (e.g. weight less than 85 per cent of that expected).4.10.1 anorexia nervosa

SECTION 4  clinical syndromes of adult psychiatry 788
2 Intense fear of gaining weight or becoming fat, even though 
underweight.
3 Disturbance in the way in which one’s body weight or shape is 
experienced.
4 In postmenarchal females, there is amenorrhoea of at least three 
menstrual cycles.
DSM-IV subdivides anorexia nervosa as follows.
1 Restricting type, without regular binge-eating or ‘purging’ behav-
iour (in the United States this term includes self-induced vomit-ing and the misuse of diuretics as well as laxatives).
2 Binge-eating/purging type.
Anorexia nervosa in males
The reduced frequency of anorexia nervosa in the male might lead 
one to surmise that the disorder is likely to differ between the sexes in its aetiology, clinical manifestations, and prognosis. Y et, there are remarkable similarities between the sexes as regards the age of onset and the speciﬁ  c features of the psychopathology.
(91–93)  For

(91–93)  For 
example, the male patients tended to select a diet which was low in fattening foods and resorted to subterfuges to dispose of food, such as self-induced vomiting and purging, and strenuous exercising. They expressed a fear of fatness and considered themselves over-weight, even when they were thin.
Of course there are fundamental biological differences which 
inevitably alter the manifestations of the endocrine disorder in the male and, to a lesser extent, the nutritional disorder. T esticular function, as gauged by the urinary output of testosterone, is dis-turbed in male patients when they are emaciated. Refeeding leads to a partial correction of this abnormality.
(91) The body composi-
tion of the mature male differs from that in the female; he has a lower reserve of adipose tissue so that protein depletion occurs more rapidly when he loses weight.
The relative resistance of the male against developing anorexia

The relative resistance of the male against developing anorexia 
nervosa remains a mystery. It is even unclear whether the sex difference is likely to be due to biomedical factors or psychosocial differences. It has been suggested that young females often become preoccupied with ‘fatness’ because of its reproductive, biological, and social signiﬁ  cance, whereas young males are more concerned 
with their musculature and its signiﬁ  cance for strength, dominance, 
and masculinity.
(92) These differences are linked with the frequency 
of dieting among adolescent girls and its rarity in boys.(94)
In a series of male patients with ‘primary’ anorexia nervosa 
most of the patients reported problems with sexuality.(95) Sexual

most of the patients reported problems with sexuality.(95) Sexual 
anxieties had been present with respect to heterosexual as well as homosexual behaviour. One quarter admitted homosexual tendencies. Almost all were relieved by the loss of libido following weight loss. The authors concluded that males with atypical gender role behaviour had an increased risk of developing anorexia nervosa in adolescence.
There are only a few follow-up studies of anorexia nervosa in 
males. In one impressive study, 27 patients were followed up for a minimum of 2 years and a mean of 8 years.
(96) Expressed in terms of

(96) Expressed in terms of 
the Morgan–Russell categories of general outcome, a good outcome was found in 44 per cent, an intermediate outcome in 26 per cent, a poor outcome in 30 per cent, and no deaths. Only a few predictors of outcome were identiﬁ  ed: disturbed relationships with a parent in childhood led to a poor outcome, and the occurrence of previous 
sexual activity was associated with a good outcome. The outcome in males was remarkably similar to that in females.
(94)
The natural outcome is deﬁ  ned as the long-term results of the 
illness or disease process. The clinical prognosis is the difﬁ  cult task 
of forecasting the future course and ﬁ  nal outcome of the illness in 
an individual patient.
Outcomes from follow-up studies in anorexia nervosa

There have been comprehensive appraisals of follow-up studies in anorexia nervosa
(97) which have put forward criteria for the 
near-perfect follow-up study, which in practice are seldom fully met. Among these criteria are precision in the diagnostic features, the use of standardized interviews, 100 per cent success in tracing the patients, and a sufficiently long follow-up to determine eventual outcome. An arbitrary interval of at least 4 years was previously set
(21) and most recent studies have adhered to this 
recommendation. Several groups of investigators have adopted measures of outcome based on the Morgan–Russell scales.
(98) Their 
use gives rise to three possible categories of general outcome based on body weight and menstrual function: ‘good’ , ‘medium’ , and ‘poor’ .
In a review comparing three British studies and one Swedish

In a review comparing three British studies and one Swedish 
study,
(99) each with a mean follow-up of 5 to 6 years, it was found 
that the patients treated in Bristol had a better outcome than those treated at the Maudsley Hospital in London. The explanation is one of selection bias already mentioned: the Maudsley patients had all required inpatient treatment, whereas in the Bristol series the majority were outpatients. The third British study, from St George’s Hospital, London, showed a quality of outcome intermediate between the other two.
The Swedish study was extended by two later follow-ups at 15 
and 33 years. On the one hand, the percentage of good outcomes gradually increased and the percentage of poor outcomes dimin-ished. On the other hand, the death rates increased with time; after 33 years the total mortality from anorexia nervosa or suicide was 18 per cent. Slow recovery was the rule: only 29 per cent of patients

recovered in less than 3 years of illness, another 35 per cent within 
3 to 6 years, and the remainder took much longer with recovery after 12 years being rare.
(99) The Maudsley series of patients 
was also extended to a mean follow-up of 20 years. There was a reduction in the percentage of patients with a poor outcome, but an increase in the mortality rate close to that of the Swedish study.
(100)
Prognostic predictors of outcome
In the long-term Maudsley study a poorer outcome was predicted by an older age of onset, a longer duration of illness, the presence of neurotic traits in childhood, personality problems, and the occurrence of relationship difﬁ  culties within the family.
(100)
Comparison of mortality rates
In a review of 42 studies the aggregate annual mortality rate from 
anorexia nervosa was found to reach 0.56 per cent on average.(101)
Complications of anorexia nervosa accounted for 54 per cent of deaths, suicide for 27 per cent, and other causes for 19 per cent.

789
A fair measure of consistency has been found in different parts of 
the world, especially when allowance is made for selection biases: in Denmark 0.5 per cent per annum (younger patients), in Sweden 0.75 per cent per annum, in the United States 0.66 per cent per annum, and in the United Kingdom 0.75 per cent per annum.
(100)
Follow-up studies in early-onset anorexia nervosa
In a series of 60 patients in Berlin with a mean age of onset of 14.7, followed up for at least 4 years, recovery occurred in 68 per cent of patients but there was a 6.6 per cent mortality over a mean of 4.8 years,
(102) a higher rate than was found in the Danish study

(102) a higher rate than was found in the Danish study 
already mentioned. A study of teenage-onset anorexia nervosa had the advantage of community screening and the use of a com-parison group. At a 10-year follow-up the outcome was good in 43 per cent, intermediate in 29 per cent and poor in 20 per cent. There were no deaths. Strikingly there was a poor psychosocial outcome in half the anorexic patients with high dependence on state beneﬁ  ts.
(103)
Theander(104) has provided good advice and useful deﬁ  nitions:
Clinical experience has repeatedly shown that patients with anorexia 
nervosa can recover after a period of illness amounting to more than 10 years.
A distinction should be made between a ‘chronic’ illness and

A distinction should be made between a ‘chronic’ illness and 
a long-standing illness. The word ‘chronic’ should be restricted to a continuous illness of more than 15 years’ duration because up to then the patient is still capable of a full recovery. The term ‘protracted’ is preferable for an illness of prolonged duration but not as long as 15 years.
Treatment: review of evidence
In this review the evidence underpinning treatments for anorexia nervosa will be presented. Whenever possible the clinician should use a treatment whose efﬁ  cacy has been established, but he will 
seldom be able to conﬁ  ne himself to such treatments. For example, 
in the case of the severely malnourished patient who presents as an emergency an admission to the specialized eating disorder unit may be the ﬁ  rst necessary step, even though it has sometimes been

in the case of the severely malnourished patient who presents as an emergency an admission to the specialized eating disorder unit may be the ﬁ  rst necessary step, even though it has sometimes been 
argued that the evidence underpinning inpatient treatment is limited. In the majority of patients presenting with only moderate weight loss it is possible to select a treatment with a higher level of evidence for its efﬁ  cacy. Such a treatment is family therapy, the 
treatment of choice in an adolescent patient.
Some cautionary words are called for on the subject of evidence-
based psychiatry. For anorexia nervosa, there is no truly speciﬁ  c 
treatment in the sense of effecting a long-term ‘cure’ . The choice

treatment in the sense of effecting a long-term ‘cure’ . The choice 
of treatment should be determined by the needs of the patient at the time when she presents for treatment and will vary according to the severity of the illness and the stage it has reached. It is wise to take into account the patient’s age, her maturity, and her person-ality. A given treatment may be indicated for a short period only at the end of which the therapeutic aims need to be reviewed. Such a selective approach has sometimes been called the ‘stepped care’ approach but this concept can be misleading. The steps may not be in the same direction. They may go down as well as up. For example, a patient may be in urgent need of refeeding and if she makes good progress the next stage would consist of consolidating her improvement. If she is unfortunate, however, earlier priorities 
will reassert themselves.

A tendency to decry the beneﬁ  ts of treatment in anorexia nervo-
sa ﬁ rst appeared in the early 1990s, and in more recent years cries 
of despair have become ever shriller. T o some extent this is a side 
effect of the treatment evaluation industry which has unintention-ally caused confusion between the usefulness of treatments on the one hand and the solid scientiﬁ  c evidence for their efﬁ  cacy on the 
other. In an ideal world the two would be the same. In an illness such as anorexia nervosa they often are not, as will be illustrated further on.
A key member of the treatment evaluation industry in the United 
Kingdom is the National Institute for Clinical Excellence
(NICE).
(105) NICE has developed a hierarchy for the strength of

(NICE).
(105) NICE has developed a hierarchy for the strength of 
the evidence underpinning various treatments, as described in Chapter 1.10. I is the strongest level of evidence, followed by Ia, IIa, IIb, III, and IV , the last being the lowest level. Anorexia nervosa is an area of care, which particularly requires Clinical Practice guide-lines because of substantial dangers to life and physical health and some clinical uncertainties. So far NICE has failed to provide the required ‘statements to assist practitioner decisions about appropriate health care for speciﬁ  c clinical circumstances’ . NICE 
has not recognized the solid evidence favouring family therapy in adolescents (according it only Grade B in an ill-deﬁ  ned set of

has not recognized the solid evidence favouring family therapy in adolescents (according it only Grade B in an ill-deﬁ  ned set of 
Grades A, B, and C for clinical guidelines). Family therapy should be regraded as A. NICE has also failed to identify the speciﬁ  c value 
of a specialized eating disorder service in patients with a risk to physical health and life. This should have been graded at least as B, 
or as (I) using the system of clinical recommendations described in Chapter 1.10. The correction of severe malnutrition requires a specialized eating disorder service rather than the involvement of 
a physician and medical unit (proposed by NICE) whose treatment 
is usually restricted to tube-feeding. NICE has also failed to recog-nize the value of other treatments, according them only a Grade C, implying there have been no good clinical studies.
The randomized controlled trial (RCT) has been idealized as the

The randomized controlled trial (RCT) has been idealized as the 
‘gold standard’ for the level of evidence. The absence of such evi-dence for a given treatment does not signify that this treatment lacks 
efﬁ cacy. Some colleagues write and speak as if treatments other than 
those conﬁ  rmed by RCT are not worthy of consideration. In truth 
they may well be effective, but the evidence for this is hard to come by. An effect of concentrating on RCTs and ignoring sound clinical 
evidence, is the conclusion reached by one authority that evidence-
based treatment of anorexia nervosa is ‘barely’ possible. This isto ignore the fact that there are essential treatments for whichevaluation by RCT has not yet been possible, because of insupera-ble ethical obstacles or limited patient compliance.
RCTs are particularly problematic in the assessment of treat-

ments for patients with anorexia nervosa. For example, the NICE guidelines do not mention the role of a specialized eating disorder service, although there are oblique references to ‘professionals with specialist experience of eating disorders’ and ‘a place for inpatient 
management’ . Specialized eating disorder units (EDUs) long ago graduated to providing a broad service not conﬁ  ned to inpatient 
treatment but including daycare and outpatient treatment. It is 
important to evaluate the beneﬁ  ts of a specialist eating disorder 
service, and this is not mentioned in the NICE Guidelines. There 
has been only one study randomizing low weight patients to inpa-
tient or outpatient treatments,
(96) as the difﬁ  culties are obvious.4.10.1 anorexia nervosa

SECTION 4  clinical syndromes of adult psychiatry 790
A balanced view needs to be taken towards the role of RCTs in 
the evaluation of treatments in anorexia nervosa. There has recently 
been a swing of the pendulum in the reverse direction. Some 
researchers have reached the surprising conclusion that RCTs in 
anorexia nervosa are so difﬁ  cult that they should be considered as 
‘premature’ in view of their cost and the failure of some of hem.(106)
An important reason why researchers may fail to complete a 
satisfactory RCT is the patient’s behaviour in the course of the trial. 
The anorexic patient’s resistance to treatment may extend to sabo-
taging the basic requirements of the treatment trial itself, e.g. com-
pliance with the treatment and the follow-up assessments. These 
problems are difﬁ  cult to eliminate entirely. Nevertheless RCTs are 
still possible if the researchers are assiduous in following-up their 
patients. Evaluators of research trials should see that the perfect

patients. Evaluators of research trials should see that the perfect 
trial in anorexia nervosa is a contradiction in terms. The pessimists 
favouring the abandonment of RCTs should remember that new 
ideas can emerge unexpectedly during the course of a trial, thus 
pointing the researcher towards fresh treatment approaches 
capable of being retested at a later date.
In the remainder of this section levels of evidence for the efﬁ  cacy 
of treatments will be discussed, even when they are not considered 
by NICE.
Family therapy
Family therapy is the main treatment to have been carefully evalu-
ated in anorexia nervosa, having now been tested in a number of 
randomized controlled trials. Any one of these trials has its imper-
fections, but taken as a body of evolving evidence, family therapy 
should be seen as the method of choice for treating anorexic

should be seen as the method of choice for treating anorexic 
patients with an early age of onset. Some of these trials will be 
summarized in order to illustrate ethical and technical difﬁ  culties, 
as well as the strength of the evidence.
(a) The ﬁ  rst controlled trial of family therapy
The ﬁ rst controlled trial of family therapy  was begun at the 
Maudsley Hospital in the early 1980s on a series of 57 patients.(107)
The principles of the family therapy have been incorporated in the 
Maudsley model, which has been adopted by researchers in the 
United States who have reached broadly similar conclusions.(108)
One assumption of the Maudsley model of family therapy is that 
the family is ineffective in helping the patient eliminate her symp-
toms and might indeed contribute to their maintenance, because

toms and might indeed contribute to their maintenance, because 
family life has become so organized around a potentially life-threat-
ening problem. It is considered essential to correct the patient’s 
starvation by assisting the parents to take control of their child’s 
eating until her weight has returned to normal.
The ﬁ  rst Maudsley trial had to overcome ethical objections to a 
randomized allocation bearing in mind the severity of the illness. 
Risks were minimized by ﬁ  rst ensuring that the patients’ weight 
loss had been corrected during an admission to an eating disorders 
unit. Family therapy itself commenced on discharge and aimed at 
the prevention of relapse. The outpatient family therapy was 
administered for 1 year and the patients were assessed on the com-
pletion of 1 year’s treatment and 5 years later.

The 57 anorexic patients were subdivided into three groups 
according to recognized prognostic criteria. This showed that the 
beneﬁ  ts of family therapy were conﬁ  ned to one of the three sub-
groups, namely patients with the age of onset less than 19 years and 
a duration of illness less than 3 years.Patients in each subgroup were randomly allocated to family 
therapy or the control treatment which consisted of a supportive 
and problem-centred individual therapy. Most important in assess-
ing progress was body weight. The Morgan-Russell scales were 
utilized to obtain categories of general outcome and measures of 
adjustment along ﬁ  ve dimensions: nutritional status, menstrual 
function, mental state, psychosexual adjustment and socio-eco-
nomic status, as well as their mean, the ‘average outcome score’ .

(i) Group 1: early age of onset (short history)
A tendency for the patients to lose weight on discharge from 
hospital was reversed more readily in patients in receipt of family 
therapy. The superiority of family therapy was demonstrated by 
a higher weight at the end of 1 year’s treatment (Fig. 4.10.1.2). 
Family therapy was also demonstrated to be more beneﬁ  cial on the 
Morgan-Russell scales in terms of more good outcome categories 
and a higher average outcome score.
(ii) Group 2: patients with late age of onset
In this group the effect of the two therapies was reversed 
(Fig. 4.10.1.3). Individual therapy appeared to result in a greater 
weight gain than family therapy but signiﬁ  cant only at a 6-months 
follow-up.
It was concluded that family therapy was more effective than

It was concluded that family therapy was more effective than 
individual therapy in patients whose illness began before the age 
of 19 years and had lasted less than 3 years.
(b)  Beneﬁ  cial components of family therapy in adolescents: 
the second Maudsley RCT(109)
The ﬁ  nding that family therapy is effective in younger patients with 
anorexia nervosa has led to a search for the effective components 
of this therapy. Many family therapists consider that it is important 
to understand the way the family functions. Others, however, prefer 
a symptom oriented approach with an emphasis on helping the 
parents to manage their child’s problem.(43) The relative impor-
tance of these two components of family therapy has been investi-
gated by comparing conjoint family therapy with separated family 
therapy.(109) In conjoint family therapy (CFT) the whole family is

therapy.(109) In conjoint family therapy (CFT) the whole family is 
seen together in the treatment sessions. In separated family therapy 
(SFT) the parents are seen together and the same therapist also sees 
Fig. 4.10.1.2 Group of patients whose illness had an early onset and was of short 
duration. FT, family therapy; IT, individual therapy; ABW, average body weight.

791
the patient separately for therapy and support. In CFT it is possible 
to observe and interpret family transactions, whereas this is not 
possible in SFT. The two treatments share the therapeutic advice 
for the parents to sustain a united approach aimed at improving 
their child’s eating pattern.
The RCT was between CFT and SFT, given for 1 year on an out-
patient basis. Forty adolescent patients were enrolled, most of them 
severely underweight (mean BMI 15.4).
In the course of the year the beneﬁ  ts of CFT and SFT were simi-
lar with considerable gains in weight (mean 8.2 kg) and marked 
improvements in the Morgan/Russell average outcome scores. 
Signiﬁ  cant differences in the patients’ responses to CFT and SFT 
were only obtained when treatment outcome was analysed sepa-
rately in patients of high and low expressed emotion (EE) families. 
The patients within the high EE group allocated to SFT reached a 
signiﬁ  cantly higher weight at follow-up (99.9 per cent ABW) than

signiﬁ  cantly higher weight at follow-up (99.9 per cent ABW) than 
those in the CFT group (85.8 per cent ABW).
(c) RCT undertaken in Stanford, USA(108)
This trial was also on adolescent patients, this time comparing two 
courses of family therapy: one lasting for 6 months (10 sessions) 
and the other for 1 year (20 sessions). The aim of the study was
to ascertain whether the duration of the family therapy exerted a 
critical effect on outcome.
The therapy was given according to the Maudsley Model, but the 
US study had a number of advantages, including a larger patient 
population (86 adolescents) and hence a greater statistical power. 
The therapy was given by therapists trained on a manual-based 
form of family therapy.
In comparison with the 2000 Maudsley Study(109) the patients 
were not so ill, (mean BMI 17.1). The principal measures of 
outcome were body weight and the eating disorder examination

outcome were body weight and the eating disorder examination 
(EDE). There were no statistically signiﬁ  cant differences between 
the two treatments.
The authors concluded that the short-term course of family was 
as effective as the long-term one for adolescents with a short 
duration anorexia nervosa. However, patients with more severe 
obsessive compulsive thinking, or coming from non-intact fami-
lies, beneﬁ  ted from the longer treatment.Strictly speaking, this RCT as such did not provide evidence
of beneﬁ  t from family therapy as there was no alternative form
of treatment as a control. Nevertheless the outcomes at the
end of 1 year’s treatment were highly satisfactory with improve-
ments not reported previously in natural outcome follow-up
studies.
(d) Enduring beneﬁ  ts of family therapy
(i) 5-year follow-up with the ﬁ  rst Maudsley RCT(110)

studies.
Patients who took part in the original Maudsley RCT of family 
therapy were followed up 5 years after the end of treatment
in order to look for evidence of long-term beneﬁ  t. Follow-up 
information was obtained on all 57 patients.(110) Apart from 
three deaths, there was a further overall improvement mainly 
attributable to the natural outcome of anorexia nervosa.
Within the subgroup of patients with early onset/short history, 
the mean weight achieved was 103 per cent ABW in patients
who had received family therapy. On the Morgan/Russell scale,
signiﬁ  cantly greater improvement after family therapy was still dis-
cernable with a higher proportion of patients achieving a ‘good’ 
outcome and a higher average outcome score.
(ii) 5-year follow-up with the Maudsley adolescent RCT(112)

Of the original 40 patients 38 agreed to be reassessed. Compared 
with the end of treatment there were more patients in the good 
outcome category and fewer in the poor outcome category, and a 
further increase in weight. There were no deaths. The main 
purpose of this study had been to compare CFT and SFT. There 
was a signiﬁ  cant difference between the two groups in the number 
of patients who resumed normal menstruation, higher in the SFT 
than in the CFT group. The ﬁ  ndings at 1 year in patients from 
families with raised levels of maternal criticism (high EE) were still 
evident at 5 years. This group had done less well at the end of treat-
ment in terms of weight and resumption of menstruation if they 
had been offered CFT.
(iii) 4-year follow-up with the US (Stanford) adolescent RCT(113)

Of the original 86 adolescent patients 71 were followed up. The 
long-term clinical outcome was good. Again there was little
difference between patients treated with short-term or long-term 
family therapy. The BMI at follow-up for the short-term was
20.6, and the group as a whole showed good psychosocial
functioning.
(e) Family therapy conclusions
There is now a strong body of evidence from RCTs that family 
therapy beneﬁ  ts younger patients with anorexia nervosa. The 
strength of the evidence in favour of family therapy has grown 
because of the increasing size of the patient populations tested: 
21 in the 1987 Maudsley study, 40 in the 2000 Maudsley study, and 
86 in the 2005 Stanford study.
1 From the search for speciﬁ  c components of the family therapy in 
the Maudsley studies, it can be concluded that the therapy should

the Maudsley studies, it can be concluded that the therapy should 
not be aimed at ‘changing the family’ but rather at helping them 
manage a sick family member.
2 Differences in the patients’ responses to CFT and SFT were 
detected when there was a separate analysis for treatment 
outcome in patients in high and low expressed emotion (EE) 
families. From this it was concluded that SFT is the more appro-
priate treatment in families with high expressed emotion.Fig. 4.10.1.3 Group of patients with relatively late onset of anorexia nervosa. FT, 
family therapy; IT, individual therapy; ABW, average body weight.

SECTION 4  clinical syndromes of adult psychiatry 792
3 The Stanford study points towards the family therapy of
shorter duration (6 months) being acceptable, except in the case of patients with obsessive compulsive thinking or in splitfamilies.
4 Finally, it is impressive that the quality of the clinical outcome 
increases in the long-term follow-ups. The patients in the 1987 Maudsley study showed the best outcome at the end of5 years. This is not simply due to an expected good natural out-come, as the beneﬁ  ts of family therapy were still evident after
5 years.
Cognitive behavioural therapy
A theory for faulty cognitions maintaining the illness has been put forward by Fairburn et al .
(114) The argument for examining 
the role of faulty cognitions in anorexia nervosa is inescapable. The original description of perceptual and conceptual disturbances in anorexia nervosa was put forward by Bruch in 1962.
(5) It was

(5) It was 
appreciated that faulty attitudes to body size contributed in part to the patient’s determination to reduce her food intake and lose weight. These observations led to the development of cognitive behavioural therapy (CBT) for anorexia nervosa. At first the evidence of its beneﬁ  t relied on clinical impressions and case 
reports.
(115) In recent years there have been valiant attempts to 
assess CBT in adult anorexic patients. It must be said, however, that these studies have met with limited success.
(a)  CBT as a post-hospitalization treatment
The most fruitful RCT was conducted at the New Y ork State Psychiatric Institute.
(116) The design depended on the random allo-

cation to CBT or the control treatment nutritional counselling (NC) of outpatients after discharge from an inpatient programme. Patients were eligible to enter the outpatient trial when they reached at least 90 per cent of ideal body weight. 33 who were eligible were randomly assigned to one or other treatment. The value of each treatment was assessed by its ability to prevent a relapse, deﬁ  ned as 
a fall in weight below a BMI of 17.5, or the development of medical or psychiatric complications.
Overall treatment failure was counted as the number of patients 
who had relapsed plus those who had dropped out from the treat-ment. The main ﬁ  nding is that the CBT group had a lower relapse 
and dropout rate and a better clinical outcome than the NC group.

(b)  Comparison of CBT with a non-speciﬁ  c supportive clinical 
management (NSCM)
This study was conducted in Christchurch, New Zealand.(117)
In this randomized controlled trial three therapies were compared:
1 CBT2 Interpersonal psychotherapy
3 Non-speciﬁ  c supportive clinical management (NSCM).
The hypothesis was that the two specialized psychotherapies 
would be more effective than NSCM.
56 women were enrolled in the study. In fact the mean weights at 
baseline were not all that low (mean BMI 17.3). Twenty sessions were provided over a course of 20 weeks. The main assessments were a Global Assessment of Functioning (GAF) scale designed by the authors, body weight and the EDE.
The improvement in the group as a whole was perhaps disappoint-

ing with mean weight gains of 2.2 kg for CBT to 4.0 kg for NSCM. The hypothesis was not upheld and the speciﬁ  c therapies were
less good than the non-speciﬁ  c supportive clinical management.
The main lesson from this study is that good general clinical care combined with supportive psychotherapy can be at least as goodas CBT.
(c)  Multi-centred US study of CBT on its own or combined 
with medication(106)
An RCT was conducted in three well-established centres in the 
United States (White Plains New Y ork, Minneapolis, and Stanford). In the original design there were three treatment groups:
1 Medication only2 CBT only3 Combined CBT and medication
Altogether 122 patients were randomized to one or other of these

Altogether 122 patients were randomized to one or other of these 
treatments. The patients were mainly adult. Their mean BMI (17.7–17.9) suggested the patients were not extremely thin. Intensive treatment was offered for up to 1 year. The patients were withdrawn from the study if they were ‘treatment failures’ . There were only low rates of completion: 27 per cent of the patients 
allocated medication, 43 per cent in the CBT group and 41 per cent 
in the combination group.
The methodological problems prevented an evaluation of the 
relative effectiveness of the treatments. The overall conclusions were somewhat pessimistic:
‘It appears premature to conduct randomized controlled trials for adults with anorexia nervosa  until the reasons for poor acceptance and 
high dropout rates . . . have been identiﬁ  ed, and methods to remedy 
these serious problems have been devised’ .

In fact the investigators were unlucky with the high rate of non-
compliance; other studies offering psychotherapy to adult anorexic patients did not encounter such high dropout rates.
(118)
The specialist eating disorder service

(118)
There is evidence that the treatment of anorexia nervosa is superior in specialized eating disorder units (EDUs) to that of general psy-chiatric units (adult or adolescent) or general medical units. The EDU comprises a team of professionals with training in the treat-ment of patients with anorexia nervosa and in maintaining the particular therapeutic ethos that is required. An EDU used to provide mainly inpatient care, but in recent years this has been extended to day and outpatient care. The clinical staff consist of a wide range of personnel including a psychiatric leadership and a trained nursing staff. The psychotherapeutic skills may vary but should include family therapy. The ethos of the EDU needs to combine a mix of therapeutic empathy for the patient with the ability to persuade her to return to a normal weight and eating habits. It is essential that the EDU nurse should be able to combine 
these skills.

This ethos was established in EDUs set-up in London in the 
1970s and 1980s, particularly at St George’s Hospital, the Royal Free Hospital and the Maudsley Hospital. It is from there that evidence has arisen for the effectiveness of a specialized eating disorder service.
An ambitious study from St George’s Hospital, London, initially 
aimed at evaluating the advantages of three treatment settings.
(96)
Fortunately the study incorporated a control group and the

793
comparison with the active treatment groups yielded the most 
important results. The four groups were as follows:
1 Inpatient treatment: 4 months on average followed by outpatient 
psychotherapy.
2 Outpatient treatment combining individual and family therapy.3 Outpatient group therapy.
4 The control group provided no treatment at the EDU after a 
‘one-off’ evaluation.
90 patients were randomly allocated to one or other of the four 
options. The study began in the mid-1980s when uncertainty in the subject still warranted from an ethical point of view a random allocation to four groups, including one in which no treatment was provided but the patients returned to the care of their general practitioners. There were methodological difﬁ  culties. The patients 
sometimes dropped out of the treatment when it was not what they wished: out of 30 patients offered inpatient treatment, only 18 accepted it.
At 1 year follow-up there were few clear-cut differences between

At 1 year follow-up there were few clear-cut differences between 
the patients in the three treatment groups: the inpatients’ weights were similar to the outpatients. The clearest ﬁ  nding was that 
patients allocated to any one of the three treatment groups fared 
much better than those allocated to the one-off evaluation session 
only.
The main lesson from this valiant study is that care within an 
ED service, whether inpatient or outpatient, and irrespective of the speciﬁ  c treatment modality, is superior to treatment received 
outside an ED service.
(a) Day care and community treatment
There is a paucity of controlled trials of day programmes. An exception is the comparison of inpatient and day treatment carried 
out in Edinburgh.
(119) A traditional inpatient programme, aimed

(119) A traditional inpatient programme, aimed 
strictly at weight gain, was compared with a more permissive day programme stressing open communication and patient autonomy. The day programme consisted of intensive psychological treat-ments and was available on 4 days each week. 32 patients who would have merited admission to hospital were randomly allocated to the day programme or the inpatient programme. Although sta-tistically signiﬁ  cant differences were not found between the two 
methods of treatment, the author reported interesting trends in 
improved outcome using the Morgan/Russell scales. The only advantage conferred by inpatient treatment was a slightly greater

improved outcome using the Morgan/Russell scales. The only advantage conferred by inpatient treatment was a slightly greater 
weight gain. In contrast, the day programme was more popular with patients who preferred to have a greater say in their rate of weight gain. There was also a greater return of personal autonomy.
(b) Inpatient treatment
Inpatient treatment in recent years has attracted a bad press. It has been argued that there are few RCTs, which have thrown any light on the beneﬁ  ts of inpatient treatments. This is a blinkered approach

because RCTs addressed to some of the questions, are either inap-propriate or ethically impossible to carry-out. An example of a largely inappropriate question from a clinical point of view is the comparison of inpatient and outpatient treatment in anorexia nervosa because the indications and the patient’s suitability for each are very different. It is justiﬁ  ed to state this categorically 
because there now exists solid clinical experience to show what can be achieved by inpatient treatment. The limitations of inpatient treatment are that the beneﬁ  ts may last only a number of months 
when there is a variable likelihood of relapse. A useful research 
question would be to identify patients who are most likely to relapse 
after inpatient treatment. The ﬁ  rm statement made above is war-
ranted because of the valiant study by Crisp and his colleagues
(120)
previously discussed. T oday this study would probably not be possible from an ethical point of view.

(120)
The most obvious beneﬁ  t from inpatient treatment in an EDU 
is that this is the surest and safest method of improving the patient’s nutrition and correcting her weight loss, thereby revers-ing physical complications, and sometimes saving her life .
In various cohort studies the weight gain has varied around 12 kg in 12 weeks.
(120–122) There are no comparable rapid improvements 
with outpatient treatments, not even  family therapy  in ad olesce nts.
There have been a small number of RCTs in anorexia nervosa in 
addition to the Crisp et al study, and they have addressed narrower 
questions. For example, a comparison of two different inpatient treatment programmes has yielded the helpful ﬁ  nding that a strict 
operant conditioning programme offers no advantages over a ‘lenient’ programme.

(123) The value of a specialized eating disorder 
unit in inducing weight gain was also demonstrated in a cohort of patients admitted to the Maudsley Hospital in 1990. They had pre-viously been admitted to a general psychiatric or medical unit, and information on their previous weights was obtained. In the case of the Maudsley admissions the mean weight rose from 65.8 per cent average body weight (abw) to 90.4 per cent abw; in comparison the admissions elsewhere only led to a mean weight gain from 64.4 to 75 per cent abw.
(122)
(c) Compulsory treatments
A study of the use of compulsory treatment in patients admitted to the Eating Disorders Unit at the Maudsley Hospital, comprised 81 patients or16 per cent of admissions. Section 3 of the Mental Health Act, valid for up to 6 months, was the most frequently applied section.
(121) The compulsorily admitted patients were

(121) The compulsorily admitted patients were 
compared with a group of voluntary patients. The need for a compulsory admission was found to have two dimensions—the presence of a severe illness and a rejection of treatment. The com-pulsory patients gained at least as much weight as the voluntary patients but required a longer admission for them to return to a near-normal weight. The compulsory patients represented a selected group by virtue of a more entrenched reluctance to accept treatment. Accordingly it was predicted that in the long term they would fare less well than voluntary patients. The mortality rate of these patients was determined by the National Register, which provided the data at a mean of 5.7 years after the index admission. T en out of 79 detained patients had died in comparison with two out of 78 voluntary patients, a statistically signiﬁ  cant difference. 
The deaths among the compulsory patients were all due to anorexia

The deaths among the compulsory patients were all due to anorexia 
nervosa or one of its nutritional complications. Thus the mortality rate among compulsory patients was extremely high at 2.17 per 
cent per annum, presumably skewed because of the selection 
factors. Compulsory treatment is an obvious example of the inap-propriateness of an RCT.
Treatment: advice on management
It is not possible for the clinician to conﬁ  ne his treatment of 
anorexia nervosa to those methods that have been subjected to4.10.1 anorexia nervosa

SECTION 4  clinical syndromes of adult psychiatry 794
randomized control trials. This does not mean that his treatment is 
ineffective or unsupported by evidence. The evidence has to be derived from other kinds of studies. They should not be dismissed as mere clinical experience if they can be supported by evidence-based clinical or experimental observations.
The main obstacle to treatment
The avoidance of treatment by the patient is part and parcel of anorexia nervosa and accentuated by her capacity for denial (see p. 783 of this chapter). There have been attempts to predict the likely level of the patient’s compliance with treatment. For example, a ‘transtheoretical model of change’ is aimed at improving the patient’s motivation by overcoming ambivalence while at the same time avoiding confrontation.
(124) Different stages in the patient’s approach

(124) Different stages in the patient’s approach 
to treatment have been recognized: precontemplation, contempla-tion, preparation, action, maintenance, and relapse prevention. Motivational enhancement therapy is at an early stage of develop-ment with only preliminary information on its impact on treatment outcome.
At our present level of knowledge it is simplest to ascertain the 
patient’s attitude to treatment through the mental state examina-tion. At the initial interview she should be asked what weight she would be willing to reach. At this stage it is best to refrain from challenging the patient’s weight threshold, even though it will be well below a reasonable therapeutic goal. Having ascertained the limited degree of compliance, the clinician needs to develop a strat-egy to improve it gradually as treatment proceeds. It is poor clinical 
practice to place all the onus on the patient herself for accepting or

practice to place all the onus on the patient herself for accepting or 
rejecting a package of treatment at the ﬁ  rst interview, or even at a 
later stage. ‘Engaging’ the patient in treatment is an essential part of most psychotherapeutic methods including CBT.
(115) Another tac-
tic for improving the patient’s co -operation is to enlist the help of 
close members of the family. Y oung patients are likely in any case to require a family treatment.
Inpatient treatment
Although inpatient treatment is less often employed nowadays it will be described ﬁ  rst because it is most important in patients who 
present as emergencies with an urgent need to preserve life and correct serious physical and psychiatric complications.
(a) Indications for admission
X It is tempting to specify a BMI threshold for admission, but it

X It is tempting to specify a BMI threshold for admission, but it 
should be remembered that the BMI can only provide a very rough guide with many exceptions. If the BMI is below 14 admis-sion should always be considered, all the more if there has been rapid weight loss during recent weeks. Indeed a BMI of 16 may cause anxiety if it represents a drop in weight from a BMI of 21 in the course of 2 or 3 months. Close attention should be given to the physical manifestations of malnutrition, especially hypogly-caemia and electrolyte disturbances.
XThe BMI may be totally unreliable in patients who have developed oedema as the result of malnutrition, causing a vicarious weight gain, which may deceive the patient and even the clinician into a false sense of security.
X The BMI is also less reliable in children and adolescents, espe-

cially if their growth in height has been retarded thus distorting the calculation for the BMI towards a falsely reassuring value.X Dangerous or disabling physical complications:
X Emergencies may result from low blood glucose levels, hypoka-
laemia or hyponatraemia. The electrolyte disturbances are most likely to occur in the presence of self-induced vomiting or laxative abuse. Hyponatraemia may be induced by polydipsia. Signs of proximal myopathy also indicate a need for admission, as do the occurrence of anaemia, low platelet counts (sometimes accompanied by purpura) and impaired liver function tests.
X Severe depression or obsessional behaviour may also arise in part

X Severe depression or obsessional behaviour may also arise in part 
as complications of malnutrition. Suicidal ideas may require admission, but persistent depression of lesser severity may also be an indication, because it renders the patient less amenable to outpatient psychological treatments, as does severe obsessional behaviour affecting the patient’s eating pattern.
X Intractable self-induced vomiting or laxative abuse or deter-
mined fasting may require a greater supervision than is possible in an outpatient setting. These behaviours are less disconcerting in patients with bulimia and at a reasonable weight, but a severe weight loss makes it probable that vomiting will result in electro-lyte disturbances or other physical complications.
X The decision to admit is often determined by the patient not 
engaging in the recommended outpatient psychological treat-ment when the malnutrition persists several months to 1 year.

X Y oung patients with a retarded puberty (premenarchal anorexia 
nervosa) should elicit an urgent correction of malnutrition, especially if there is evidence of retarded growth and short stature. There is a narrow window of opportunity for regaining stature, which may depend partly on bone age but it is safest to assume that after the age of 16 the probability of resuming growth becomes increasingly limited, especially in girls.
The great advantage of treating a patient in a specialized eating 
unit is the certainty that considerable beneﬁ  t will accrue, including 
a substantial gain in weight, so long as the patient can be persuaded to remain in hospital.
(120)
(b) Nursing and dietary care

(120)
Inpatient treatment will include a wide range of psychotherapeutic interventions (individual, group, and family) as well as occupa-tional therapy and an educational programme. But the sheet anchor of successful treatment is a well-trained nursing staff working as a team. The role of the medical staff is one of maintaining a high level of expectation that the patient’s weight will be restored to a normal (or healthy) level. It is necessary to give the nursing staff moral support so that they can develop their conﬁ  dence and skills.
There are two main components to the nurses’ treatment: their

There are two main components to the nurses’ treatment: their 
psychotherapeutic input and their supervisory role. The latter should never be draconian. The nursing team establish a relation-ship of trust with the patient and get to know her personal needs and concerns. The nurses should also be acutely aware of the anorexic patient’s tendency to avoid food and exercise excessively. 
The treatment programme should stress the supportive aspects of 
the nurse’s relationship with her patient rather than the undoubted need for careful supervision. The nurse will come to rely on the daily weight record to monitor the success of her treatment as the weight chart should show a smoothly rising curve. All meals are taken in the ward: thus the anorexic patients constitute a group in which peer interactions take place. The meal is taken in the presence

795
of one or more nurses also seated at the table. The patient learns 
that she is expected to consume all the food placed before her.
A detailed protocol for the refeeding programme has been 
produced by Andersen and his group.(120) It is not only the patient 
who tends to underestimate the food requirements to restore her weight to normal. Metabolic studies have demonstrated that for each kilogram of weight gain a surplus calorie balance of 7500 cal is needed.
(111) It is prudent to begin with a modest calorie intake 
of 1200 to 1500 cal daily during the ﬁ  rst 7 days in order to avoid the

of 1200 to 1500 cal daily during the ﬁ  rst 7 days in order to avoid the 
complications of hypophosphataemia and acute gastric dilation. Thereafter the caloric intake is gradually increased and may rise to 4000 cal. daily. The best diet is that consisting of a wide range of foods including carbohydrate and fat-containing foods. Concentrated foods (e.g. Build-up, Complan, Scandishake, Fortisip, Ensure Plus) may be used to achieve a high caloric intake. The aim is to achieve a positive energy balance of at least 1500 cal daily, leading to a weekly weight gain of 1 to 1.5 kg.
(c) Assessment of progress

Weighing should be a standardized daily procedure before break-fast after the patient has emptied her bladder and while wearing light night clothes. A paradoxical psychological improvement, with a diminution in concern with body size and shape, occurs with weight gain. The improvement is partly through the correction of malnutrition and partly the result of the ‘exposure treatment’ whereby the patient gradually accepts a higher body weight.
(d) Medication

Exceptionally the patient’s tension and depression do not improve and there is a continued resistance to food. It may then be helpful to prescribe moderate doses of olanzapine (not more than 10 mg daily), carefully avoiding a fall in blood pressure, which is a risk in the emaciated patient. In the case of persistent depression, treat-ment with an antidepressant may be indicated. However, anti-depressants are often ineffective in the presence of malnutrition, and by themselves do not assist the patient to gain weight.
(e) General measures
Inevitably the patient will ﬁ  nd it irksome to forego home visits

Inevitably the patient will ﬁ  nd it irksome to forego home visits 
during the early period of weight gain. Therefore interesting and therapeutic activities should be provided through group meetings, occupational therapy, and social interactions. Visiting is generally encouraged unless the visiting parents are subjected to emotional appeals to take her home. They may then be asked to postpone their visits or reduce their duration. The monotony can be relieved when the patient’s weight gain is on course by providing accompa-nied outings avoiding mealtimes.
The aim is to restore body weight to a healthy level within 8 to 
10 weeks; a further period (usually 2 weeks) in hospital is needed to allow the patient to test her ability to maintain her weight by eating in a general dining room or going on home leave for two or more days at a time. The aim is to effect a smooth transition to day care or outpatient treatment.
Compulsory treatment in anorexia nervosa

The management of patients reluctant to accept essential therapeu-tic goals requires that they should be gradually engaged in a genuine alliance. However, there remain a minority of patients with whom this strategy fails and whose health and life become endan-gered. For them, compulsory treatment should be considered.
(121)A compulsory admission to hospital is indicated not only when patients threaten suicide or suffer from a life-threatening malnutri-tion, but also when they fail to respond to simpler measures such as outpatient treatment or day care, or in the event of avoiding treat-ment altogether. Ill health persisting over the course of several months or the development of serious physical complications (e.g. water and electrolyte imbalance, hypoglycaemia, or myopathy) should also elicit compulsory admission if the patient cannot be persuaded to accept inpatient treatment voluntarily.

The evidence points to the usefulness of a compulsory admission 
in appropriate circumstances in so far as the patients respond well in the short term. Nevertheless, a patient who has required a compulsory admission carries a higher risk, so that it is essential to safeguard her through a long follow-up.
Day and community treatment
The Edinburgh trial of a day patient programme has already been discussed. At the T oronto Hospital a day hospital programme for eating disorders has been established since 1985.
(125) and is now 
offered on 4 days a week.
The goals are as follows:
1 A normalization of disturbed eating behaviour and weight gain.2 The identiﬁ  cation of psychological and familial processes that 
serve to perpetuate the eating disorder.
Two meals and a snack are provided during the treatment hours.

Two meals and a snack are provided during the treatment hours. 
The staff take turns to supervise the patients during meal times. The psychological treatment consists of intensive group therapy addressing disturbed behaviours around eating and weight, and more general conﬂ  icts.
The clinical advantages of day treatment are a reduction in the 
dependence of patients who need to be able to function outside the hospital. The group treatment provides an atmosphere of mutual support while permitting interventions through group pressures. A wide range of patients can be admitted but those with medical or suicidal risks will elicit inpatient care instead. When patients succeed in reducing their disturbed eating behaviours they may ‘act out’ by self-harm. The clinical staff may ﬁ  nd their skills severely 
taxed by the continuous staff/patient interaction.
A home oriented service extended to outpatient and day care, has

A home oriented service extended to outpatient and day care, has 
been devised by Robinson (2006) for an area of North London (1.2 million). A wide range of treatments were devised including family interventions and carer support. The educational needs of mem-bers of the multi-disciplinary team are well described as are admin-istrative and ﬁ  nancial issues. Robinson’s book includes an audit on 
the use of hospital and hostel beds requiring only 4–5 total beds per million population per year.
Outpatient psychotherapies

In the event of a patient’s weight loss being less than 20 per cent of her healthy weight, it may be possible to obtain a therapeutic response by outpatient treatment, including attendance at non-specialist general psychiatric clinics or child/adolescent psychiatric services. The feasibility of this approach will depend on the avail-ability of appropriate psychotherapeutic resources. The clinician should guard himself against imaginary conﬂ  icts between a psycho-
therapeutic approach and recording the weight of the patient. It is never justiﬁ  ed to accept apparent compliance with psychotherapy 
if the patient’s weight continues to decline.4.10.1 anorexia nervosa

SECTION 4  clinical syndromes of adult psychiatry 796
(a) Family treatments
(i) Conjoint family therapy
The frequency of the sessions is determined by clinical need: it 
averaged 10.5 over the course of 1 year in the Maudsley trial. There are three stages to the therapy:
1 In the ﬁ  rst phase the parents are urged to identify their future 
joint attitude to the feeding pattern that should be adopted by their daughter. With a younger patient the therapist assumes that the parents would initially need to take control of their child’s eating.
2 During the second phase the parents are urged to be present 
together at each meal so that they can reinforce each other’s efforts in the practical task of ensuring an improved food intake and a steady weight gain.
3 When the patient’s weight is under control, responsibility for

3 When the patient’s weight is under control, responsibility for 
continued weight gain is handed back to her. Discussions can then commence on more normal family concerns. With an adolescent patient the main focus is on achieving increased autonomy. The eventual aim is to establish healthy relationships with her parents without the eating disorder as a medium for communication.
(ii) Separated family therapy
As in conjoint family therapy the parents are given direct advice on how to manage their daughter’s eating problem. The patient herself is provided with individual psychotherapy. The therapist provides counselling about abnormal attitudes to weight and emphasizes the weight issue until steady progress has been made. This method is often preferred by the patient and her parents, largely because it avoids confrontation. It is also easier to gain access to the patient’s fears and conﬂ  icts.
(b) CBT
CBT has much in common with other methods of treatment

(b) CBT
CBT has much in common with other methods of treatment 
including the refeeding programme described under inpatient treatments. It relies on building a positive therapeutic alliance between therapist and patient.
The patient’s weight and food intake is monitored at each session 
and she is told her weight. She is encouraged to think of food as medication and to follow a meal plan. The patient is educated in the disturbances of bodily and psychological function consequent on the state of starvation. The content of the therapy may be divided into two ‘tracks’ . The ﬁ  rst track includes an examination of the 
behaviours adopted by the patient in order to reduce her weight. The second track is more concerned with psychological themes such as self-esteem, perfectionism, interpersonal functioning, and family conﬂ  icts. By asking the patient to give her reasons for 
specific behaviours, the therapist discovers faulty beliefs and

specific behaviours, the therapist discovers faulty beliefs and 
assumptions on her part. For example, the ‘anorexic wish’ is the patient’s wish to recover from her disorder without gaining weight. She is gently persuaded that this is an impossible aim because her real psychological difﬁ  culties will remain inaccessible so long as her 
experiences are clouded by starvation and dieting. The patient also expresses a fear of ‘losing control’ meaning that she will run the risk of overeating and become fat. It is explained to the patient that her rigid ‘control’ overeating deprives her completely of choice, and that far from being in control the reality is the converse. It is also useful for the therapist to analyse the pros and cons of maintaining the disorder of anorexia nervosa. The patient often 
feels more uncomfortable at confronting the hidden rewards of remaining thin.
Having ascertained the particular meanings of attitudes and

Having ascertained the particular meanings of attitudes and 
behaviours for the patient, she is helped to ﬁ  nd more adaptive ways 
of achieving healthier goals, including more relaxed normal eating and weight gain.
(c) Dynamic psychotherapy: therapeutic model
(i) Crisp’s model of anorexia nervosa as a ﬂ  ight from growth
Crisp has explained how his programme of treatment is based on 
his model of anorexia nervosa as a refuge from puberty, which the patient has found overwhelming. The youngster reverses her pubertal development by limiting her intake of food.
(126) His treat-

ment initially involves an intensive inpatient programme lasting 10 to 12 weeks followed by outpatient treatment for up to 6 years. The advantage of this extensive programme is that it enables the patient to accept gradually an increase in weight while facing up to the feelings of panic and helplessness that originally led her to arrest her puberty through self-starvation. This interpretation is presented to the patient and to her family so that they come to see the psychotherapy as a way of solving the problems.
The model is a useful one even within a more limited outpatient

The model is a useful one even within a more limited outpatient 
psychotherapeutic setting. Some patients will readily identify their distress when overwhelmed by powerful sexual feelings or when confronted with personal and social responsibilities perceived as the result of growing up. The aims of the psychotherapy are to support the patient while she is beginning to abandon the psycho-biological regression of anorexia nervosa. In addition she is encour-aged to broaden her perception of herself in ways that are no longer wholly dependent on her physical appearance but include an improved sense of competence and self-esteem. She is helped to tackle personal and social problems from which she had previously escaped so that she can address her own and her parents’ concerns about sexuality.
Ethical and medico-legal issues
In the United Kingdom the Mental Health Act Commission(127)
has clariﬁ  ed many of the doubts in the minds of clinicians and

has clariﬁ  ed many of the doubts in the minds of clinicians and 
social workers called upon to consider a compulsory admission under the Mental Health Act 1983. It recognized that anorexia nervosa is a mental disorder within the meaning of the Act and that in some patients their ability to consent may be compromised by fears of obesity or denial of the consequences of their actions. The Mental Health Act Commission concluded that when the patient’s health is seriously threatened by food refusal she may be detained in hospital so as to treat the self-imposed starvation. The Commission went as far as to state that nasogastric feeding can be a medical process forming an integral part of the treatment for anorexia nervosa, notwithstanding that nasogastric feeding is seldom required.

Preventive measures have been aimed at eating disorders generally rather than just anorexia nervosa. The main approach has been school-based intervention programmes educating adolescent girls into the risks of dieting and other methods of weight control. The commonest outcome has been an increased knowledge about

797
eating disorders without a change in the behaviours, such as 
dieting, likely to cause them. One controlled study, six weekly sessions were provided by teachers on a wide range of topics cover-ing attitudes and behaviours relevant to eating disorders including a ‘non-dieting approach’ . Positive changes were detected at a 6-month follow-up but they were modest in size and poorly 
sustained.
(128)
Currently there are active campaigns by the Academy of Eating 
Disorders and Beat Eating Disorders (UK) to encourage the fash-ion industry not to employ thin models. Unilever has adopted a policy not to employ models with a BMI less than 18.5. John Lewis requires models to be not less than size 12.
Robinson, P .H. (2006). Community treatment of eating disorders . John Wiley, 
Russell, G.F.M. (1993). Social psychiatry of eating disorders. In Principles 
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78. McLoughlin, D.M., Spargo, E., Wassif, W.S., et al. (1998). Structural and 
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 84. Rieger, W., Brady, J.P ., and Weisberg, E. (1978). Hematologic
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111. Russell, G.F.M. and Mezey, A.G. (1962). An analysis of weight gain in 
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112. Eisler, I., Simic, M., Russell, G.F.M., et al. (2007). A randomized

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pp. 94–144. Guilford Press, New Y ork.

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178, 216–21.
119. Freeman, C. (1992). Day patient treatment for anorexia nervosa. 
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of anorexia nervosa. In Handbook of treatment for eating disorders

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Press, New Y ork.4.10.1 anorexia nervosa

SECTION 4  clinical syndromes of adult psychiatry 800
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in anorexia nervosa: short-term beneﬁ  ts and long-term mortality. 
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123. T ouyz, S.O., Beumont, P .J.V ., Glaun, D., et al. (1984). A comparison 
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144, 517–20.
124. Prochaska, J.O. and Di Clemente, C.C. (1992). The transtheoretical 
approach. In Handbook of psychotherapy integration  (eds. J.C. Norcross 
and M.R. Goldfried), pp. 300–34. Basic Books, New Y ork.
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and P .E. Garﬁ  nkel), pp. 354–60. Guilford Press, New Y ork.

126. Crisp, A.H. (1997). Anorexia nervosa as ﬂ  ight from growth: assessment 
and treatment based on model. In Handbook of treatment for eating 
disorders  (2nd edn) (eds. D.M. Garner and P .E. Garﬁ  nkel), pp. 248–77. 
127. Mental Health Act Commission. (1997). Guidance on the treatment of 
anorexia nervosa under the Mental Health Act 1983 , pp. 1–6. Mental 
Health Act Commission, Nottingham.
128. Stewart, D.A., Carter, J.C., Drinkwater, J., et al. (2001). Modiﬁ  cation of 
eating attitudes and behaviour in adolescent girls: a controlled study. The International Journal of Eating Disorders ,29, 107–18.
4.10.2 Bulimia nervosa
Origins of the concept
The history of the diagnosis bulimia nervosa begins as recently as

The history of the diagnosis bulimia nervosa begins as recently as 
1979. It was in this year that Russell published his now seminal paper ‘Bulimia nervosa: An ominous variant of anorexia nervosa’
(1)

(1)
in which he described 30 patients (28 women and 2 men), seen between 1972 and 1978, who had three major features in common. First, they had recurrent episodes of uncontrolled overeating; second, they regularly used self-induced vomiting or laxatives as means of weight control; and third, they had a morbid fear of becoming fat. Russell described many other features shared by these patients, including a history of anorexia nervosa (present in 80 per cent), the presence of severe depressive symptoms, and the fact that in most cases their body weight was in the healthy range. He noted that the disorder tended to run a chronic course and that it was ‘extremely difﬁ  cult to treat’ . Finally, he suggested that this 
clinical picture should be viewed as a syndrome, distinct from anorexia nervosa, and he proposed the term ‘bulimia nervosa’ .

It is difﬁ  cult to exaggerate the importance of Russell’s paper. Its 
greatest contribution was perhaps its prescience in that it crystal-lized out from among the range of eating disorders seen in clinical practice a subgroup of patients that was just starting to become more common; it identiﬁ  ed its central features; and it gave it an 
appropriate name.Events since 1980
Events gathered pace in the 1980s. In 1980 a syndrome termed ‘bulimia’ was included in DSM-III.
(2) This was intended to denote 
the type of patient that Russell had described, although its diagnos-tic criteria proved to be overly inclusive. In 1987, the criteria were reﬁ ned and brought more in line with Russell’s original concept. 
The syndrome was also renamed bulimia nervosa.
(3) Also in the

(3) Also in the 
early 1980s evidence mounted that bulimia nervosa might be com-mon and this led to a spate of studies of its prevalence. At the same time reports were published describing the successful treatment of these patients, the two most promising approaches being a speciﬁ  c 
form of cognitive behaviour therapy and the use of antidepressant drugs. By the mid-1980s, both treatments had been tested in the ﬁ rst of what has become a large series of controlled trials.
Now, three decades later, the diagnosis bulimia nervosa is included 
in both DSM-IV
(4) and ICD-10,(5) its prevalence is established, 
aspects of its aetiology are beginning to be understood, and much has been learned about its treatment.
Classiﬁ  cation and diagnosis
The classiﬁ  cation of the eating disorders and their principal diag-

nostic criteria are shown in Table 4.10.2.1. Bulimia nervosa is one of the two main eating disorders recognized in DSM-IV and ICD-10, the other being anorexia nervosa (discussed in Chapter 4.10.1). In addition, in DSM-IV there is a residual category termed ‘eating disorder not otherwise speciﬁ  ed’ . This is reserved for 
eating disorders of clinical severity that do not meet the diagnostic criteria for anorexia nervosa or bulimia nervosa.
(6) In ICD-10, 
various eating disorder categories other than anorexia nervosa and bulimia nervosa are recognized (for example, atypical anorexia nervosa, atypical bulimia nervosa, overeating associated with other psychological disturbances), although these concepts have never been adequately deﬁ  ned or differentiated.
The relationship between the three DSM-IV diagnoses is repre-

sented diagrammatically in Fig. 4.10.2.1. The two overlapping inner circles represent anorexia nervosa (the smaller circle) and bulimia nervosa (the larger circle) respectively, the area of potential overlap being that occupied by those people who would meet the diagnostic criteria for both disorders but for the rule that the diagnosis of anorexia nervosa trumps that of bulimia nervosa (see Table 4.10.2.1). Surrounding these two circles is an outer circle which deﬁ  nes the 
boundary between having an eating disorder, a state of clinical sig-
niﬁ cance, and having a lesser, non-clinical, eating problem. It is this 
boundary that demarcates what is, and is not, an eating disorder. Within the outer circle, but outside the two inner circles, lies eating disorder not otherwise speciﬁ  ed (eating disorder NOS).
In DSM-IV a new eating disorder diagnosis was proposed termed

In DSM-IV a new eating disorder diagnosis was proposed termed 
‘binge eating disorder’ . It is designed to denote an eating problem characterized by recurrent binge eating in the absence of the extreme weight-control behaviour seen in bulimia nervosa. Since binge eating disorder is a provisional diagnostic concept, it is currently an example of eating disorder NOS.
The two schemes for classifying eating disorders encourage the 
view that anorexia nervosa and bulimia nervosa are distinct clinical states. Consideration of their clinical features and course over time does not support this.
(7) Binge eating disorder aside, patients with 
anorexia nervosa, bulimia nervosa, and eating disorder NOS have

801
many features in common, most of which are not seen in other 
psychiatric disorders, and studies of their course indicate that patients migrate between these diagnoses over time: indeed, temporal migration is the norm rather than the exception. This temporal movement, together with the fact that the disorders share the same distinctive psychopathology, has led to the suggestion that 
the current diagnostic scheme is a poor reﬂ  ection of clinical reality 
and that common ‘transdiagnostic’ mechanisms may be involved in the maintenance of eating disorder psychopathology.
(8)
The great majority of patients with bulimia nervosa are female and most are in their 20s (although the age range is between 10 and 60 years). In considering the psychopathology of the disorder, a distinction may be drawn between its ‘speciﬁ  c’ and ‘general’

features. The former comprises features that are largely peculiar to eating disorders (for example, self-induced vomiting, the over-evaluation of shape and weight), whereas the latter consists of fea-tures seen in other psychiatric conditions (for example, depressive symptoms). The clinical features of bulimia nervosa are similar in men and women and in those with and without a history of anorexia nervosa.
Speciﬁ  c psychopathology
(a) Dieting and binge eating
The eating habits of patients with bulimia nervosa are characterized 
by strict dieting punctuated by repeated episodes of binge eating (see Fig. 4.10.2.2). The dieting is extreme and it is governed by multiple self-imposed dietary rules. These rules tend to be applied to all aspects of eating, including when to eat, what to eat, and how much to eat. As a result, the food eaten (when not binge eating) is restricted in quantity and range.
Recurrent episodes of ‘binge eating’ interrupt this dieting. (The

Recurrent episodes of ‘binge eating’ interrupt this dieting. (The 
term binge eating denotes discrete episodes of eating that have two characteristics: ﬁ  rst, an unusually large amount of food is eaten, Table 4.10.2.1  Classiﬁ  cation of eating disorders and their principal 
diagnostic criteria.
Classiﬁ  cation of eating disorders
X Anorexia nervosa
X Bulimia nervosa
X Eating disorder not otherwise speciﬁ  ed (eating disorder NOS)
Binge eating disorder (a provisional new diagnosis, currently subsumed under 
eating disorder NOS)
Principal diagnostic criteria
Anorexia nervosa1  Over-evaluation of shape and weight (i.e. judging self-worth largely, or 
exclusively, in terms of shape and weight)
2  Active maintenance of an unduly low body weight (e.g. body mass 
index < 17.5)
3  Amenorrhoea (in post-menarcheal females who are not taking an oral 
contraceptive). This criterion is often omitted.
Bulimia nervosa1  Over-evaluation of shape and weight (i.e. judging self-worth largely, or

Bulimia nervosa1  Over-evaluation of shape and weight (i.e. judging self-worth largely, or 
2 Recurrent binge eating (i.e. recurrent episodes of uncontrolled overeating)3  Extreme weight-control behaviour (e.g. strict dieting, frequent self- induced 
vomiting, or laxative misuse)
4 Diagnostic criteria for anorexia nervosa are not metEating disorder not otherwise speciﬁ  edEating disorders of clinical severity that do not conform to the diagnostic 
 criteria for anorexia nervosa or bulimia nervosa
Binge eating disorderRecurrent binge eating in the absence of the extreme weight-control 
 behaviour seen in bulimia nervosa
(Reproduced from Fairburn, C.G. Cognitive Behaviour Therapy and Eating Disorders, copy-
right 2008, Guildford Press, NY .)

behaviour seen in bulimia nervosa
Fig. 4.10.2.1 A schematic representation of the relationship between anorexia nervosa, bulimia nervosa, and eating disorder NOS (Reprinted fr om Fairburn, C.G. 
and Bohn, K. Eating disorder NOS (EDNOS): an example of the troublesome “not otherwise speciﬁ  ed” (NOS) category in DSM-IV, Behaviour Research and Therapy , 43, 
691–701, copyright (2005), with permission from Elsevier).Anorexia nervosa
Bulimia nervosaEating disorder NOS
Not a “case” Eating disorder “case” Not a “case”4.10.2 bulimia nervosa

SECTION 4  clinical syndromes of adult psychiatry 802
given the circumstances; and second, there is a sense of loss of con-
trol at the time. Some patients with eating disorders have similar episodes of uncontrolled overeating that do not involve the con-sumption of objectively large amounts of food. These episodes are sometimes referred to as ‘subjective binges’ although technically speaking they do not meet the deﬁ  nition of a ‘binge’ .) The frequency 
and regularity of the binge eating varies. Some patients have episodes almost every day, whereas in others the episodes are intermittent. In DSM-IV , it is speciﬁ  ed that the binges should occur 
on average at least twice a week, but this is an arbitrary ﬁ  gure that 
has little discriminatory value. Among those patients in whom the binge eating is frequent, the binges have few, if any, obvious trig-gers, although there may be circumstances under which binge eating is more likely (for example, when alone at home). Among

patients in whom the binge eating is less frequent, the binges often 
have clear precipitants. These tend to be of three overlapping types: ﬁ rst, there is breaking a personal dietary rule (for example, exceed-
ing a daily calorie-limit or eating a banned food); second, there are situations which intensify concerns about shape and weight (for example, receiving an adverse comment about appearance); and third, there is the occurrence of negative moods (often as a result of interpersonal events). All three undermine the maintenance of strict dietary control.
The amount of food eaten during binges varies, both from 
patient to patient and from episode to episode. Typical episodes involve the consumption of 1000 to 2000 kcal.
(9) The food eaten generally comprises items that are otherwise being avoided. Thus

(9) The food eaten generally comprises items that are otherwise being avoided. Thus 
binges tend to be composed of energy-dense, high-fat items such as chocolate, ice cream, and pastries. Binges come to an end as a result of the combined inﬂ  uence of exhaustion, extreme fullness, a dimi-
nution of the drive to eat, and the running out of food supplies. In about three-quarters of patients they are immediately followed by measures designed to counteract the effects of the overeating, the most common being self-induced vomiting and the taking of laxatives or diuretics.
The binges are a source of considerable distress. They magnify 
these patients’ fears of weight gain and fatness, and they may result in shame and self-disgust. For this reason most binges occur in private and are kept secret from others. It is the binge eating that eventually drives these people to seek help.

(b) Purging and other forms of weight control
In DSM-IV bulimia nervosa is subdivided into two types, a purging and non-purging type. In the purging type there is regular self-induced vomiting or the misuse of laxatives or diuretics, or both, whereas in the non-purging type such behaviour (‘purging’) is either not present or it is infrequent. The majority of patients seen in clinical practice have the purging form of the disorder and it has been the focus of most research.
Self-induced vomiting is the most common form of purging. In 
most patients it only takes place after binge eating. It is generally achieved by stimulating the gag reﬂ  ex, using the ﬁ  ngers or some Fig. 4.10.2.2 A monitoring record illustrating the eating habits of a patient with bulimia nervosa. Asterisks are used to signify episodes of  eating that were viewed by the

patient as excessive. The column headed ‘V/L’ is for recording episodes of self-induced vomiting or laxative misuse.Time Food and drink consumed Place * V/L Context and comments
7.30 Glass water Kitchen   [8stone  9lbs - really gross]     
     Thirsty after yesterday 
8:10 1 bowl muesli with skimmed Kitchen *  Should have had less muesli.
 milk Black coffee    Must not binge today.  
10:35 Half banana Work -   Better - on track
 Black coffee at desk
11:45 Ham and lettuce slimline In canteen   Usual lunch
 sandwich Diet coke
6.40 Slice of chocolate cake Kitchen *  Help - I can't stop eating.
to 1/2 tub ice cream     I'm completely out of control. 
7.30 4 slices of toast with jam    I hate myself.
 Diet coke Another slide of cake 2 slices of toast with jam
 Diet coke
 Jam from jar    I am disgusting.  Why do I do  Two kit kats    this?  I started as soon as I 
 Mars bar    got in.  I've ruined another 
 Diet coke - large   V day.

Diet coke
 Diet coke - large   V day. 
9:30 Rice cake with fat-free Kitchen   Really lonely.  Feel fat and 
 cheese    unattractive.  Feel like giving up.  Diet coke       Day……Thursday………..        Date  …..March 21 ………..

803
other long object, although in more established cases it can be 
accomplished with no mechanical aid. The vomiting is repeated until patients think that they have retriev ed all the food that they can. 
Patients get extremely distressed if they are unable to vomit after binge eating: indeed, if they foresee that they may not have the oppor-tunity to vomit, they tend not to binge. A minority of patients also induce vomiting at other times, for example, following smaller epi-sodes of overeating (subjective binges) or ordinary meals or snacks.
The misuse of laxatives or diuretics is somewhat less common 
than self-induced vomiting. It takes two forms: one is to compen-sate for speciﬁ  c episodes of binge eating, like self-induced vomiting; 
and the other is as a general method of weight control (like diet-ing), in which case it is not tied to particular episodes of overeating. The number of laxatives or diuretics taken varies considerably, sometimes far exceeding the recommended dose.

None of these methods of purging is an effective method of 
weight control. Self-induced vomiting results in the retrieval of only about half to two-thirds of what has been eaten, the taking of laxatives has a minimal effect on food absorption, and diuretic-taking has none. As a result, a signiﬁ  cant proportion of each binge 
is absorbed.
The weight of most of these patients is in the healthy range (BMI 
between 20 and 25) due to the effects of the under-eating and over-
eating cancelling each other out. As a result they do not experience the secondary psychosocial and physical effects associated with maintaining a very low weight seen in anorexia nervosa.
Other forms of weight-control behaviour are practised by some

Other forms of weight-control behaviour are practised by some 
patients, including over-exercising, the spitting out of food, and the taking of repeated enemas or saunas. Over-exercising is the most common of these, but it is not nearly as prominent or as obviously pathological as in anorexia nervosa. A minority of patients ruminate, that is, repeatedly regurgitate and re-chew food that has been eaten. They may then either re-swallow the food or spit it out. This behaviour is not well-understood.
In the non-purging type of bulimia nervosa there is no vomiting 
or misuse of laxatives or diuretics, or they occur infrequently. Instead, there is sustained and marked dietary restriction outside the binges. This is both a response to the binge eating and contrib-utor to it, in that this type of eating increases the risk of further episodes. In all other respects the two subtypes of the disorder are similar.
(c) Attitudes to shape and weight

A characteristic set of attitudes to shape and weight is the other distinctive element of the speciﬁ  c psychopathology of bulimia

nervosa. Equivalent attitudes are found in anorexia nervosa and most cases of eating disorder NOS. These attitudes are often described as the ‘core psychopathology’ of eating disorders. They are characterized by an overconcern with shape and weight in which there is a fear of weight gain and fatness that is generally accompanied by a pursuit of weight loss and thinness. Underlying this psychopathology is the tendency to judge self-worth largely, or even exclusively, in terms of shape and weight. Whereas it is usual to evaluate self-worth on the basis of perceived performance in a variety of domains of life (such as interpersonal relationships, work, sport, artistic ability, etc.), people with anorexia nervosa or bulimia nervosa evaluate themselves primarily in terms of their shape and weight. These attitudes and values constitute a good example of an overvalued idea.Most features of bulimia nervosa can be understood as being

secondary to these attitudes to shape and weight. The dieting, purging, and over-exercising are obvious secondary features. In addition, there are direct behavioural expressions of these concerns. For example, many patients repeatedly weigh themselves and scrutinize their appearance in mirrors. Others avoid any knowledge of their weight while being acutely sensitive about their appearance. Some avoid others seeing their body and some even avoid seeing it themselves. This can have a major impact on social and sexual relationships.
The concerns about shape and weight, and eating, have a major 
effect on others in the patient’s immediate environment. Meals are often times of tension and social events which involve eating may be avoided. The feeding of children may be affected
(10) and their 
growth may be impaired(11) (see Chapter 9.3.6).
General psychopathology

General psychiatric symptoms are prominent in bulimia nervosa; more so than in anorexia nervosa. The nature of the comorbid symptoms also differs. Depressive features are particularly striking: indeed, the level of depressive symptoms in bulimia nervosa is equivalent to that seen in major depressive disorder. Anxiety symp-toms are also encountered, many of which are directly related to the eating disorder; for example, there is often pronounced anxiety about eating in public. Obsessive-compulsive features are some-times present, although they are less common than in anorexia nervosa. Similarly, social functioning is less impaired.
The depressive features of bulimia nervosa deserve special men-
tion. In most patients the depressive features can be attributed to the presence of the eating disorder but in a subgroup there appears to be an independent coexisting, but interacting, clinical depres-

sion. Features suggestive of such coexisting clinical depressions 
include the following: recent intensiﬁ  cation of depressive features 
(in the absence of any change in the eating disorder or the patient’s circumstances); pervasive and extreme negative thinking (i.e. broader in content than concerns about eating, shape, and weight); hopelessness in general (i.e. seeing the future as totally bleak, seeing no future, resignation); recurrent thoughts about death and dying; suicidal thoughts; guilt over events in the far past; a decrease in involvement with others over and above any impairment that already accompanied the eating disorder (e.g. ceasing to see friends); loss of interest in activities that had been pursued despite the eating disorder (e.g. ceasing to listen to music; ceasing to read newspapers or follow the news); and a decrease in drive and initiative.
These coexisting clinical depressions often go undetected since

These coexisting clinical depressions often go undetected since 
they are viewed as characteristic of bulimia nervosa. This is unfor-tunate for two reasons: ﬁ  rst, they interfere with the treatment of 
the eating disorder; and second, they are readily treated with anti-depressant drugs (unlike the secondary depressive features).
A minority of patients with bulimia nervosa have ‘impulse-
control’ problems, such as the overconsumption of alcohol or drugs, or repeated self-harm (e.g. cutting). Some of these patients also meet diagnostic criteria for borderline personality disorder (see Chapter 4.12.2). The prevalence of such features varies accord-ing to treatment setting: they are unusual in community samples, whereas they are more frequent among patients seen in specialist treatment centres.4.10.2 bulimia nervosa

SECTION 4  clinical syndromes of adult psychiatry 804
Much more common than frank personality disorders are 
two traits which are also seen in anorexia nervosa. The ﬁ  rst is low 
self-esteem. This generally antedates the eating disorder, although it is often exaggerated by it. Many patients with bulimia nervosa describe longstanding doubts about their worth and ability, irre-spective of their accomplishments. The second is perfectionism, that is, imposing on oneself inordinately high personal standards in a range of domains (for example, work, sport, personal conduct). Since many of these standards are unachievable, it is common for these patients to give long histories of viewing themselves as perpetually failing.
Physical features

There are few physical abnormalities in bulimia nervosa. Body weight is unremarkable in the majority of patients and thus the physical effects of starvation are rarely seen. Nevertheless, menstru-al abnormalities or amenorrhoea are present in about a quarter of patients. These are likely to be secondary to the disturbed eating since they generally respond to the successful correction of the eat-ing disorder. On laboratory testing endocrine abnormalities are sometimes encountered and these tend to be mild versions of those found in anorexia nervosa. Fertility appears not to be affected.
Frequent purging, and especially the combination of vomiting 
and laxative misuse, results in ﬂ  uid and electrolyte abnormalities in

and laxative misuse, results in ﬂ  uid and electrolyte abnormalities in 
some patients. These abnormalities are varied in nature but most often consist of some combination of hypokalemia, hyponatremia, and hypochloremia. The patients appear to accommodate to these abnormalities since medically serious complications (for example, 
cardiac arrhythmias) are much less common than might otherwise 
be expected given the laboratory ﬁ  ndings. Some patients experi-
ence intermittent oedema particularly if there is a sudden decrease in the extent of their purging.
Localized physical abnormalities include erosion of the dental 
enamel (especially from the lingual surfaces of the front teeth) among those who have vomited for many years; traumatic calluses on the knuckles of the hand of those who use their ﬁ  ngers to induce 
the gag reﬂ  ex (Russell’s sign); and enlargement of the salivary

the gag reﬂ  ex (Russell’s sign); and enlargement of the salivary 
glands, especially the parotids, probably as a result of chronic inﬂ ammation. A small proportion of patients have raised serum 
amylase levels usually due to an increase in the salivary isoenzyme.
Relationship to other disorders
Anorexia nervosa and eating disorder NOS
Bulimia nervosa has many features in common with anorexia nervosa and eating disorder NOS, particularly the characteristic attitudes to shape and weight and the behaviour that arises directly as a result.
(12) In most cases, bulimia nervosa is preceded either by

(12) In most cases, bulimia nervosa is preceded either by 
frank anorexia nervosa (in about a quarter of cases) or an anorexia nervosa-like form of eating disorder NOS. While movement from bulimia nervosa to anorexia nervosa is unusual, progression on to some form of eating disorder NOS is common. Whether it is appro-priate to view such patients as having recovered from one psy-chiatric disorder and developed another is a moot point: rather, it would seem more appropriate to view them as having a single evolving eating disorder.
There is some evidence of co-aggregation between bulimia 
nervosa, anorexia nervosa, and eating disorder NOS with there being increased rates of all three diagnoses among the relatives of 
probands with either condition.
(13)
Obesity
Few patients with bulimia nervosa are overweight or have obesity. On the other hand there is evidence of raised rates of parental and premorbid obesity.
(14) Obesity is an unusual sequel of the disorder

(14) Obesity is an unusual sequel of the disorder 
although this may be because those at most risk of obesity are less likely to recover and so continue to suppress their weight.
As noted above, depressive features are common in bulimia nervosa and they may antedate the eating disorder. The same is true of anxiety and anxiety disorders. Most family studies have found a raised rate of affective disorder among these patients’ relatives whereas little is known about the familial relationship between bulimia nervosa and the anxiety disorders.
(15) There is a raised rate 
of alcohol and drug abuse among patients with bulimia nervosa and a raised rate among these patients’ relatives.
(15) Substance 
abuse rarely antedates the eating disorder but this is to be expected given the age of onset of substance abuse disorders.
It is hazardous making personality disorder diagnoses among

It is hazardous making personality disorder diagnoses among 
those with eating disorders. This is because eating disorders have their onset in adolescence and they directly affect many of the characteristics upon which personality is judged. Thus there is a risk of overestimating the presence of personality disturbance. Nevertheless, some patients with bulimia nervosa do seem to have a coexisting personality disorder, the most common form being borderline personality disorder. Little is known about the rate of personality disturbance among these patients’ relatives although there is evidence of familial co-aggregation of anorexia nervosa and obsessional and perfectionist traits.
(15)
Diabetes mellitus

(15)
It was thought that eating disorders were over-represented among those with Type I diabetes mellitus. This is now not clear. Controlled studies in which eating disorder features have been assessed by interview rather than self-report questionnaire (the preferred method and one which minimizes the risk of false positive diagno ses)
have found little evidence of an elevated rate of anorexia nervosa although the rate of bulimia nervosa may be increased.
(16)
Distribution
The fact that it took Russell more than 6 years (1972–1978) to collect 30 cases of bulimia nervosa suggested that the disorder was not common. It is therefore remarkable that within a few years of the publication of Russell’s paper it was evident that bulimia nervosa was an important source of psychiatric morbidity among young women.
In the early 1980s large numbers of previously undetected cases 
were identiﬁ  ed using the media.
(17,18)  These cases were remarkably

(17,18)  These cases were remarkably 
similar to Russell’s, except that almost all were female and a small proportion had a history of anorexia nervosa. Most had kept their eating disorder secret for many years, and because of shame and hopelessness few had sought help. Many thought that they were the only person with this type of eating disorder. Simultaneously however, and doubtless partly as a result of the media attention,

805
there was also a sharp increase in the number of people requesting 
treatment for bulimia nervosa (see Fig. 4.10.2.3).
The marked increase in the number of patients with bulimia 
nervosa stimulated interest in the prevalence of the disorder. By 1989 over 50 prevalence studies had been conducted, many of which yielded unrealistically high prevalence ﬁ  gures as a result 
of using weak assessment and sampling procedures. Gradually methods improved with the result that estimates of the prevalence of bulimia nervosa decreased to more modest and consistent levels with the point prevalence among young adult women (aged 16 to 35 years) being in the region of 1 per cent,
(19,20) a similar ﬁ  gure 
being obtained for lifetime prevalence.(20) The prevalence of buli-

mia nervosa among men is not known. Among patient samples, male cases are unusual. Bulimia nervosa is thought to be uncom-mon in non-Western societies although few prevalence studies have been conducted and most have had signiﬁ  cant methodological 
shortcomings.
(21)
There have been few estimates of the incidence of bulimia 
nervosa, and since these have been based upon clinic rather than community samples, they are likely to underestimate the true ﬁ gures. Even today, many people with bulimia nervosa do not seek 
help. The lack of reliable community-based incidence ﬁ  gures also 
makes it impossible to know whether the disorder has become more common since the 1970s or whether the upsurge in cases in

makes it impossible to know whether the disorder has become more common since the 1970s or whether the upsurge in cases in 
the early 1980s was as a result of undetected cases being more likely to seek treatment. Data from the assessment of women in different birth cohorts suggest that the disorder has become much more common
(22) although other explanations for the apparent increase 
cannot be ruled out.
Aetiology
Development of the disorder
As noted in Chapter 4.10.1, anorexia nervosa generally starts in mid-adolescence with a period of voluntary dietary restriction which proceeds to get out of control. As a result body weight falls and a state of starvation develops. Shape and weight concerns may pre-date the onset of the dieting or develop as weight is lost.
Bulimia nervosa starts in a similar way although the age of onset

Bulimia nervosa starts in a similar way although the age of onset 
is typically some years later and shape and weight concerns usually antedate the dieting. The dietary restriction resembles that seen in anorexia nervosa and it leads to weight loss sufﬁ  cient to result in 
anorexia nervosa in about a quarter of cases. (As a result of referral bias, this proportion is higher in cases seen in specialist centres.) In the remaining cases there is also weight loss but it is less extreme. After a variable length of time (generally within 3 years) dietary control breaks down with the patient’s dieting becoming punctu-
ated by episodes of overeating. At ﬁ  rst, the episodes of overeating

ated by episodes of overeating. At ﬁ  rst, the episodes of overeating 
may be modest in size and intermittent, but gradually they become larger and more frequent. As a result, the lost weight is regained and body weight returns to near its original level. By this point the disorder tends to be self-perpetuating. At some stage in this sequence of events, self-induced vomiting and laxative misuse may be adopted to compensate for the overeating. In practice, however, both forms of behaviour have the opposite effect since belief in their effectiveness encourages a relaxation of control over eating. In those who vomit this phenomenon is exaggerated by the discovery that the process is easier after eating large amounts of food.
Predisposing factors and processes
There are many risk factors for the development of bulimia nervosa
(14) and these overlap with those for anorexia nervosa(23)
(see Table 4.10.2.2).
The risk factors may be usefully divided into a number of 
categories.

X Demographic factors—these are being female, adolescent and 
living in a Western society.
X Exposure to an immediate social environment that encourages 
dieting—this includes being brought up in a family in which there is intense interest in shape, weight, and eating as a result of one or more members either having some degree of eating disor-der or having a medical condition that affects eating or weight (such as diabetes mellitus). Extreme occupational or recreational pressures to diet also appear to be associated with increased risk (for example, ballet dancing), although there may also be an ele-ment of self-selection. Another important inﬂ  uence is parental and

childhood obesity, the rates of which are substa ntially increased in bulimia nervosa. Both are likely to sensitize individuals to their appearance and weight, and thereby make them prone to diet. There is also some evidence that puberty occurs comparatively early which may also magnify concerns about shape.
Fig. 4.10.2.3 Rates of referral to a major eating disorder centre in Toronto
(1975–1986) (Reproduced from Garner, D.M. and Fairburn, C.G  Relationship between anorexia nervosa and bulimia nervosa: diagnostic implications. In Diagnostic issues in anorexia nervosa and bulimia nervosa  (eds. D.M. Garner 
and P .E. Garﬁ  nkel), copyright 1998, Brunner/Mazel, New York).4.10.2 bulimia nervosa

SECTION 4  clinical syndromes of adult psychiatry 806
X Exposure to factors that increase the risk of psychiatric distur-
bance in general and depression in particular—these include a family history of psychiatric disorder, especially depression, and a range of adverse childhood experiences including parenting deﬁ cits and sexual and physical abuse. It was thought that sexual 
abuse was especially common among those who develop bulimia 
nervosa, but the balance of evidence suggests that the rate is no higher than that among those who develop other psychiatric disorders.
X Perfectionism and low self-esteem—both traits are common 
antecedents of anorexia nervosa and bulimia nervosa. Typically they interact resulting in feelings of incompetence and ineffectiveness.
X Family history of substance abuse—there is a raised rate of sub-

stance abuse in the families of patients with bulimia nervosa. It is not clear how this increases the risk of bulimia nervosa. Clinical observations suggest that some of those who develop bulimia nervosa learn to modulate their mood by engaging in self-harm (e.g. by cutting themselves) or by consuming large quantities of 
food, alcohol, or psychoactive drugs.
An important question is how those with anorexia nervosa are 
able to maintain strict control over their eating whereas this is not true of those with bulimia nervosa. The explanation is unclear but several processes may be of relevance. First, perfectionism is even more pronounced in anorexia nervosa and it may enhance self-control. Second, the vulnerability to obesity found in bulimia nervosa may somehow undermine dietary restraint. Third, the mood lability of bulimia nervosa may also disrupt restraint.
Contribution of genetic factors

The fact that eating disorders run in families suggests that there may be a genetic contribution. In the absence of adoption studies, twin designs have been used to establish its extent.
(24) Clinic sam-
ples show concordance for anorexia nervosa of around 55 per cent in monozygotic twins and 5 per cent in dizygotic twins, with the corresponding ﬁ  gures for bulimia nervosa being 35 and 30 per cent, 
(7,25) These ﬁ  ndings suggest a signiﬁ  cant heritability to 
anorexia nervosa but not to bulimia nervosa. Despite this, there is uncertainty as to the size of the genetic contribution to both disor-ders with there being differing point estimates and wide conﬁ  dence 
intervals. The same applies to the contributions of individual-speciﬁ  c and shared (common) environmental factors. A number of 
issues affect the interpretation of  the data. For example, there has 
been insufﬁ  cient power to detect shared environmental effects, and

been insufﬁ  cient power to detect shared environmental effects, and 
established diagnostic criteria have been broadened consi derably to increase the number of ‘affected’ twins available for analysis.
Given the clear and possibly substantial genetic contribution to 
both disorders, molecular genetic studies have been conducted to identify the underlying loci and genes. Genetic association studies 
have focussed in particular on polymorphisms in 5-HT (serotonin)-
related genes because this neurotransmitter system is important in regulation of eating and mood, but a range of other polymor-phisms have also been investigated. Despite this, no associations with eating disorders have been clearly replicated or conﬁ  rmed in a

family study or by meta-analysis. There has been one multi-centre genome-wide linkage study. It found linkage peaks for anorexia nervosa and bulimia nervosa on chromosomes 1, 4, 10, and 14. A further analysis, which covaried for related behavioural traits, identiﬁ  ed a different locus on chromosome 1, as well as loci on 
chromosomes 2 and 13. All these ﬁ  ndings await replication.
Neurobiological ﬁ  ndings
There has been extensive research into the neurobiology of eating 
disorders. This has focussed on neuropeptide and monoamine (especially 5-HT) systems thought to be central to the physiology of eating and weight regulation.
(26) Of the various central and

(26) Of the various central and 
peripheral abnormalities reported, many are likely to be secondary to the disturbed eating and associated weight loss. However, some aspects of 5-HT function and its receptors remain abnormal after recovery, leading to speculation that there is a trait monoamine abnormality which may predispose to the development of eating disorders or to associated characteristics such as perfectionism. Furthermore, normal dieting in healthy women has been shown to alter central 5-HT function, providing a potential mechanism by which eating disorders might be precipitated in women vulnerable for other reasons.Table 4.10.2.2  Principal risk factors for anorexia nervosa and 
bulimia nervosa
General factors
FemaleAdolescence and early adulthoodLiving in a Western society
Individual-speciﬁ  c factors

Family history Eating disorder of any type Depression Substance abuse, especially alcoholism (bulimia nervosa) Obesity (bulimia nervosa)Premorbid experiences Obstetric complications Adverse parenting (especially low contact, high expectations, parental discord) Sexual abuse Family dieting Critical comments about eating, shape, or weight from family and others Occupational and recreational pressure to be slimPremorbid characteristics Low self-esteem Perfectionism (anorexia nervosa and to a lesser extent bulimia nervosa) Neuroticism Anxiety and anxiety disorders Obesity (bulimia nervosa) Early menarche (bulimia nervosa) Type I diabetes (bulimia nervosa)
right 2008, Guildford press, NY .)

807
Brain functional imaging studies have identiﬁ  ed altered activity 
in the frontal, cingulate, temporal, and parietal cortical regions in both anorexia nervosa and bulimia nervosa, and there is some evidence that these alterations persist after recovery.
(27) Whether 
they are a consequence of the eating disorder or have somehow contributed to it is not known.
Maintaining factors and processes
Once established, bulimia nervosa tends to run a chronic course although it commonly evolves into eating disorder NOS. There are a number of processes which account for its self-perpetuating character. These are discussed in Chapter 6.3.2.2 (CBT for eating dis orders). They include the ongoing inﬂ  uence of the extreme con-
cerns about shape and weight; the form of these patients’ dieting, which encourages binge eating; the mood-modulating effect of binge eating; and the fact that the loss of control overeating perpetuates fears of weight gain.

The identiﬁ  cation of patients with bulimia nervosa is not difﬁ  cult 
so long as the diagnosis is considered. This is important because the shame that characterizes the disorder leads many people to delay seeking help—the average delay between onset and presenta-tion is about 5 years—and when they do present for treatment, some do so indirectly. Thus they may complain of depression, sub-stance abuse, menstrual disturbance, or gastrointestinal symptoms, rather than the eating disorder itself. The best policy is for psychia-trists to always keep in mind the possibility of bulimia nervosa when assessing female patients aged between 16 and 35 years. Negative responses to the following questions should sufﬁ  ce to 
exclude the disorder:
X ‘Do you have any problems with your eating?’
X ‘Do you have any problems controlling your eating; that is, 
problems with binge eating?’
X ‘Do you ever make yourself sick or take laxatives to control your 
weight or shape?’

Patients who present directly complain of having lost control 
over eating and their assessment is generally straightforward. It should always include an assessment of the extent to which the disorder is interfering with everyday functioning and an evaluation of general psychiatric features and especially those of depression.
The best established measure of eating disorder features is the 
Eating Disorder Examination.
(28) This interview is widely regarded 
as the ‘gold standard’ measure of eating disorders, but it is possibly too exhaustive to use on a routine clinical basis. Various self-report questionnaires are available but they provide a more basic level of assessment and they cannot be used to make a clinical diagnosis. The leading self-report measures are the Eating Disorder Inventory

(29) and the self-report version of the Eating Disorder 
Examination.(30)
No assessment is complete without weighing the patient and 
checking their height. Weighing needs to be done with considerable sensitivity because of these patients’ concerns about their weight. A physical examination is not essential unless the patient is underweight (or there are other medical indications), nor are labo-ratory tests required except in those cases in which there is reason to suspect that there might be ﬂ  uid or electrolyte disturbance.Treatment
Given that bulimia nervosa has only recently been described, there 
has been a remarkable amount of research on its treatment. Over 70 randomized controlled trials have been completed. An authori-tative meta-analysis has been conducted by the United Kingdom National Institute for Health and Clinical Excellence or ‘NICE’ .
(31)

(31)
The majority of the trials have focussed on adults with bulimia nervosa, the treatment of adolescents having received little attention, and almost all these studies have been ‘efﬁ  cacy’ rather 
than ‘effectiveness’ studies. However, there are reasons to think that their ﬁ  ndings are of direct relevance to routine patient care not 
least because the patients studied have been similar to those seen in clinical practice. Nevertheless, there is a deﬁ  nite need for effec-
tiveness studies particularly now that the main treatment options are clear.
Studies of pharmacological treatment
A variety of drugs have been tested as possible treatments for bulimia nervosa including antidepressants, appetite suppressants, anticonvulsants, and lithium. Only antidepressants have shown promise.
(a) Antidepressant medication

All the major classes of antidepressant drug have been evaluated, including tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin uptake inhibitors, and atypical antidepressants. The ﬁ  ndings have been relatively consistent and may be summa-
rized as follows (adapted from Wilson and Fairburn
(32)):
X Antidepressant drugs are more effective than placebo at reducing 
the frequency of binge eating and purging. On average, among treatment completers there is about a 50 per cent reduction in the frequency of binge eating and a cessation rate of about 20 per cent. The therapeutic effect is more rapid than that seen in depression. There is generally little change in the placebo group. The dropout rate varies but averages about 30 per cent.
X The longer-term effects of antidepressant drugs remain largely 
untested. Almost all the studies to date have been of their short-term use (16 weeks or less). The ﬁ  ndings of the few longer-term

untested. Almost all the studies to date have been of their short-term use (16 weeks or less). The ﬁ  ndings of the few longer-term 
studies suggest that outcome is poor and compliance low.
(33)
X Few studies have evaluated the effects of antidepressant drugs on 
features other than binge eating and purging. Mood improves as the frequency of binge eating declines but this effect is common to all treatments for bulimia nervosa. Antidepressant drugs do not appear to modify these patients’ extreme dieting which may account for the poor maintenance of change.
X Different antidepressant drugs seem to be equally effective, although 
there have been no direct comparisons of different drugs.
X With one exception, there have been no systematic dose-response 
studies. The exception showed that ﬂ  uoxetine at a dose of 60 mg/
day, but not 20 mg/day, was more effective than placebo.(34)

X Patients who fail to respond to one antidepressant drug may 
respond to another. There have been no drug augmentation studies.
X No consistent predictors of response have been identified. 
Pretreatment levels of depression appear not to be related to outcome.4.10.2 bulimia nervosa

SECTION 4  clinical syndromes of adult psychiatry 808
X The mechanism(s) whereby antidepressant drugs exert their 
‘antibulimic’ effects is not known. The apparent comparability of different classes of drug implicates a common mechanism but this is unlikely to be their antidepressant action since the response is too rapid and the level of depression does not predict 
outcome.
Studies of psychological treatment
(a) Cognitive behaviour therapy (CBT)
The most intensively studied psychological treatment is a speciﬁ  c 
form of CBT.(35,36) This was the ﬁ  rst promising treatment described 
and it remains the leading treatment for the disorder. The treat-ment and its rationale are described in Chapter 6.3.2.2.
CBT is conducted on an outpatient basis and involves 15 to 
20 sessions over about 5 months. It is suitable for all patients bar the small minority (less than 5 per cent) who require hospitalization.
The ﬁ  ndings of the studies of CBT (over 20 controlled trials) are

The ﬁ  ndings of the studies of CBT (over 20 controlled trials) are 
summarized below (adapted from Wilson and Fairburn
(32)):
X The drop-out rate with CBT (about 20 per cent) is less than that 
seen with antidepressant drugs. The treatment is also more acceptable to these patients than treatment with medication.
X CBT has a substantial effect on the frequency of binge eating and 
purging. On average, among treatment completers there is about an 80 per cent reduction in the frequency of binge eating, and a cessation rate of about 60 per cent.
X The effects of CBT appear to be well-maintained. Most of the 
recent studies have included a 6 to 12-month follow-up period. The relapse rates are low.
X CBT affects most aspects of the psychopathology of bulimia 
nervosa including the binge eating, purging, dietary restraint, and the over-evaluation of shape and weight. In common with other treatments, the level of depression decreases as the freque ncy

nervosa including the binge eating, purging, dietary restraint, and the over-evaluation of shape and weight. In common with other treatments, the level of depression decreases as the freque ncy 
of binge eating declines. Social functioning and self-esteem also improve.
X CBT is more effective than delayed treatment (i.e. a waiting list 
control group), other psychological treatments (other than possibly interpersonal psychotherapy—see below) and antide-pressant drugs at reducing the frequency of binge eating and purging. Among the other psychological treatments studied have been supportive psychotherapy, focal psychotherapy, supportive-expressive psychotherapy, interpersonal psychotherapy, hypnobehavioural treatment, stress management, nutritional counselling, behavioural versions of cognitive behaviour therapy, and exposure with response prevention.
X No consistent predictors of response to CBT have been identi-
ﬁ ed. Severity of symptoms at presentation, a history of anorexia

ﬁ ed. Severity of symptoms at presentation, a history of anorexia 
nervosa, low self-esteem, and the presence of borderline person-ality disorder have been associated with worse outcome in some studies but not others. However, the extent of initial response (over the ﬁ  rst 4 weeks of treatment) is a potent and potentially 
valuable predictor of outcome.
(37,38)
X The mechanism(s) of action of CBT have yet to be established 
although they appear to be mediated at least in part by a reduc-tion in dietary restraint.
(39) It also seems that the cognitive 
procedures are required for progress to be maintained since behavioural versions of the treatment are associated with a greater 
risk of relapse.(40)
X There is some evidence that the combination of CBT and antide-
pressant drugs may be more effective than CBT alone in reduc-ing accompanying anxiety and depressive symptoms.

X Simpler forms of CBT may help a small subset of patients although 
the ﬁ  ndings are not consistent. These include brief versions of the 
treatment and cognitive behavioural self-help in which patients follow a cognitive behavioural self-help programme either on their own (pure self-help) or with the guidance of a therapist (guided self-help). The programme may be delivered via a book, CD-ROM or the internet. This type of treatment is still in its infancy and it has yet to be rigorously evaluated.
(b) Interpersonal psychotherapy (IPT)
IPT is the leading alternative to CBT. This treatment was originally devised by Klerman and colleagues as a treatment for depression (see Chapter 6.3.3).
(41) It is a focal psychotherapy, the main empha-

sis of which is to help patients identify and modify current inter-personal problems. The treatment is both non-directive and non-interpretative and, as adapted for bulimia nervosa,
(42) it pays little 
attention to the patient’s eating disorder. It is therefore very differ-ent to CBT. There have been two comparisons of CBT and IPT in the treatment of bulimia nervosa and both have found that they are about comparably effective but that IPT takes 4 to 8 months longer to achieve its effects.
(40,43) The second of these studies was 
also designed to identify variables that might allow patients to be matched to CBT or IPT but none emerged.
Management of bulimia nervosa

Given that the leading treatment for bulimia nervosa is CBT, the ideal form of management is the provision of CBT by a therapist trained in its implementation. Unfortunately there is a shortage of the necessary expertise with the consequence that a ‘stepped care’ approach has been advocated on pragmatic grounds. With such an approach a simple treatment is used ﬁ  rst and only if this proves 
insufﬁ  cient a more complex and specialized intervention is pro-
vided. Three steps may be distinguished.
Step 1—Having established the diagnosis, the ﬁ  rst decision is 
whether the patient may be managed on an outpatient basis . The

whether the patient may be managed on an outpatient basis . The 
great majority (over 95 per cent of referrals to non-specialist centres) may be managed this way. Exceptions are patients at sig-niﬁ cant risk of suicide and the presence of physical complications 
necessitating inpatient or day patient care. Severe substance abuse 
requires treatment in its own right, although this can sometimes be 
integrated with the treatment of the eating disorder. For example, it is possible to adapt CBT for bulimia nervosa so that it addresses the patient’s substance abuse at the same time.
Step 2—If the patient is suitable for outpatient-based treatment, 
guided cognitive behavioural self-help, and/or antidepressant medi-cation is the next step . The former involves following a cognitive

guided cognitive behavioural self-help, and/or antidepressant medi-cation is the next step . The former involves following a cognitive 
behavioural self-help programme under the guidance of a ‘facilitator’ (a non-specialist therapist). Three cognitive behavioural self-help books are available,
(44–46)  two of which are direct transla-
tions of CBT for bulimia nervosa. There is evidence to support the use of all three and it is a matter of preference which is chosen. Each provides information about bulimia nervosa together with a self-help programme. The role of the facilitator is not to provide

809
treatment as such, as in a conventional ‘therapist-led’ treatment, 
but rather to support and encourage the patient to follow theprogramme. Thus, this is a ‘programme-led’ form of treatment, and it is this characteristic that makes it suitable for widespread dissemination. Treatment generally takes about 4 months and involves eight to ten meetings with the facilitator, each lasting up to 
30 min. It is best if the ﬁ  rst few appointments are weekly.
Guided self-help may take place in a variety of settings including 
primary care. Unfortunately only a small proportion of patients show substantial change and there are no reliable predictors of out-come. Patients who have obtained little beneﬁ  t after 4 to 6-weeks 
are unlikely to do so and should be moved on to Step 3.
Antidepressant medication is an alternative to guided self-help.

Antidepressant medication is an alternative to guided self-help. 
It is important to note that the medication is being used for its antibulimic effect not its antidepressant action. This affects the choice of drug and the dose chosen. The drug of choice is ﬂ  uox-
etine at a dose of 60 mg in the morning. It is usually well tolerated. As with guided self-help, if there has been little beneﬁ  t after 4 to 
6-weeks it is best to move on to Step 3.
A third alternative would be to combine antidepressant medi-
cation and guided self-help to see if the two augment each other. This would be a reasonable strategy although there are few data to support it.
Step 3—Patients who do not beneﬁ  t from cognitive behavioural
self-help or antidepressant medication should receive full CBT ona one-to-one basis  (see Chapter 6.3.2.2). Ideally this should be
delivered by a well-trained therapist who is used to following the protocol.
(36)

(36)
Step 4—The fourth step is for those who are still symptomatic
after having received well-delivered CBT . This step is pragmatic
since there are few research ﬁ  ndings of relevance. T o guide the 
choice of treatment, the reasons for the poor response need tobe carefully considered. Explanations include the presence of an 
undetected clinical depression; failure of CBT (which itself needs to be explained); poorly delivered CBT; poor patient compliance (which also needs to be explained); and disruption by outside events.
There are a number of different treatment options under these 
circumstances, the choice depending upon the outcome of thereassessment and the resources available. They include thefollowing:
X Stop treatment and arrange to re-evaluate the patient after an

X Stop treatment and arrange to re-evaluate the patient after an 
interval of some months. Some patients and therapists ‘burn out’ after a sustained period of therapeutic work. A break can often be helpful. Deciding to stop treatment should be a joint decision and it is not appropriate with patients who are distressed or with those whose physical or psychological well-being is a cause for concern.
X Embark upon a new psychological treatment. While the obvious 
choice is IPT, there are no grounds for supposing that patients who fail to respond to CBT will respond to IPT. Indeed, there is evidence that this is not the case.
(47) An alternative strategy 
would be to change the form of the CBT. The re-evaluation of the patient may have resulted in the identiﬁ  cation of problems

would be to change the form of the CBT. The re-evaluation of the patient may have resulted in the identiﬁ  cation of problems 
that might be amenable to cognitive behavioural procedures outside the realm of mainstream CBT for bulimia nervosa. Indeed, the fact that this occurs has led to the development of a new ‘enhanced’ form of CBT for eating disorders that is not only designed to be more potent that the earlier treatment but it also 
addresses common obstacles to change external to the eating disorder psychopathology (i.e. mood intolerance, clinical perfec-tionism, low self-esteem, and interpersonal problems).
(8,48)  It is 
also of note that this treatment is designed to be suitable for all forms of eating disorder not just bulimia nervosa.
X Arrange for day patient or inpatient treatment. In a small minor-
ity of cases outpatient treatment proves not to be sufﬁ  cient, either

ity of cases outpatient treatment proves not to be sufﬁ  cient, either 
because the disorder is resistant to outpatient-based forms of treatment or because the patient’s life circumstances are inter-fering with progress. In such cases day patient or inpatient treat-ment can be useful. Generally this involves a combination of therapeutic approaches including elements of CBT. It is essential that both day patient treatment and inpatient treatment are fol-lowed by outpatient treatment designed to ensure that progress is maintained.
Course and outcome

Much remains to be learned about the course and outcome of bulimia nervosa. It is clear from epidemiological studies thatmany people do not present for treatment. The course of theirdisorder is completely unknown. Those who do present tend todo so after a considerable period of time indicating that amongthis subgroup the disorder has a tendency to run a protracted course. On the other hand, the ﬁ  ndings of the treatment studies indicate 
that the outcome is considerably better than Russell originally sug-gested, although it must be stressed that even with CBT, the most effective treatment, only about half the patients make a full andlasting recovery.
There have been few studies of long-term course or outcome. 
A 5-year prospective study of a community sample found that
at each assessment point between a half and two-thirds of the
cases had an eating disorder of clinical severity, the majority being cases of eating disorder NOS.
(49) A 10-year follow-up study found

(49) A 10-year follow-up study found 
that about 10 per cent met diagnostic criteria for bulimia nervosa and a further 20 per cent had a form of eating disorder NOS.
(50)
There is no evidence that bulimia nervosa evolves into any other psychiatric disorder, and anorexia nervosa is a very unusualoutcome. Body weight changes little over time and, in contrastwith anorexia nervosa, the mortality rate appears not to be raised. Robust predictors of long-term course or outcome have beenidentiﬁ  ed.
We are grateful to the Wellcome Trust for its support. CGF holds a 
Principal Research Fellowship (046386). ZC and RM are supported by a programme grant (046386).
Fairburn, C.G. (ed.). (2008). Cognitive behavior therapy and eating disorders .

International Journal of Eating Disorders .
 1. Russell, G.F.M. (1979). Bulimia nervosa: an ominous variant of 
anorexia nervosa. Psychological Medicine ,9, 429–48.4.10.2 bulimia nervosa

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12. Fairburn, C.G., Cooper, Z., Bohn, K., et al. (2007). The severity and 
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New Y ork.

811
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New Y ork.
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recovery. Robinson, London.
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disorders . Guilford Press, New Y ork.
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of bulimia nervosa and binge eating disorder in young women. Archives

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of bulimia nervosa. Archives of General Psychiatry ,56, 63–9. 4.10.2 bulimia nervosa

4.11
Sexuality, gender identity, 
and their disorders
4.11.1 Normal sexual function
Normal sexual function means different things to different people. 
It is studied by a variety of disciplines: biology, physiology, psychol-ogy, medicine (in the domains of endocrinology, gynaecology, neu-rology, psychiatry, urology, and venereology), sociology, ethology, culture, philosophy, psychoanalysis, and history. There is often little liaison or cross-fertilization between these disciplines and each has its own literature and terminology. Some are regarded as ‘hard sci-ence’ , suggesting hypotheses that can be supported or rejected by experiment, observation, or measurement (evidence-based). Others are looked on as ‘soft science’ , where individual and anec-dotal evidence are the norm and are encouraged.
As space is limited, this chapter will characterize ‘normal sexual

As space is limited, this chapter will characterize ‘normal sexual 
activity’ in the Western world mainly from biological, physiological, and psychological aspects but will occasionally utilize other disciplines when they yield insights not available from the ‘harder sciences’ .
Biological determinants of normal sexual 
function
Humans are the highest evolved primates. A number of our ana-
tomical/biological features unrelated to reproduction have been described as strongly enhancing our sexual behaviour when com-pared with other primates,
(1) although recent studies have shown 
that the bonobos (pygmy chimpanzees) also use sex for reasons unconnected with reproduction.
(2)
In brief, these features are as follows:
1 The relative hairlessness of our bodies allows well-deﬁ  ned visual 
displays (see point 6 below) and enhanced tactile skin sensitivity.
2 The clitoris, which is an organ whose sole function is for inducing 
female sexual arousal/pleasure.

3 Orgasms, in both male and female, provide intense euphoric 
rewards for undertaking sexual arousal to completion. The female is able to have multiple serial orgasms.
4 The largest penis among primates, whether ﬂ  accid or erect, the 
latter acting as a good sexual stimulator of the female genitalia.
5 Concealed (cryptic) ovulation which could inﬂ  uence males to 
undertake coitus more frequently to create pregnancy and prevent cuckolding.
6 Well-deﬁ  ned visual sexual displays in the female that are not 
linked to season or fertility (i.e. breasts, pubic hair, buttocks, and lips). The everted mucous membranes of the lips serve both as a surface display (red, moist, and shiny), and for haptic stimu-lation during kissing and sucking.
7 Ability of the female to undertake sexual arousal and coitus inde-

pendent of season, hormonal status, or ovulation. Human females (unlike other primates) can and often do willingly par-take of sexual activity and coitus when they are menstruating, pregnant, or menopausal.
8 Development of large mammary glands during puberty which 
act as visual sexual signals in most cultures.
These biological determinants are augmented by socio-cultural 
factors:
1 Language, art, and music for erotic stimulation.2 Facial adornment with make-up to heighten appearance and 
sex displays (viz., lipstick).
3 Clothing, especially of the female, such as brassières to redeﬁ  ne 
the shape of breasts, corsets to redeﬁ  ne the shape of the body, 
and high-heeled shoes to elongate the legs and thrust out the Contents
 4.11.2 The sexual dysfunctions
 4.11.3 The paraphilias
 4.11.4 Gender identity disorder in adults

813
buttocks. Y oung adult males use tight trousers to create a genital 
‘bulge’ and to emphasize ﬁ  rm rounded buttocks, the latter being 
a highly sexually attractive feature to young women.
4  Perfumes and scents to enhance body aroma.
The last three features (2, 3, and 4) use artiﬁ  cial means to enhance 
normal sexual signals.(1) These biological and socio-cultural factors 
give human sexual activity an increased appetitiveness and make it more rewarding.
Sexuality as a social construct and the 
concept of sexual scripting
Laqueur(3) suggests that while the sexual biology remained 
unchanged, its expression has been inﬂ  uenced over the centuries by 
culture, social class, ethnic group, and religion. This concept, that human sexuality is a social construct, has been strongly argued by Foucault
(4) and promoted by other social constructionist authors.(5)
Gagnon and Simon(6) introduced the concept of ‘sexual scripting’ .

Gagnon and Simon(6) introduced the concept of ‘sexual scripting’ . 
Scripts organize and determine the circumstances under which sexual activity occurs, they are involved in ‘learning the meaning of internal states, organizing the sequences of speciﬁ  c sexual acts, 
decoding novel situations, setting limits on sexual responses and linking meanings from non-sexual aspects of life to speciﬁ  cally 
sexual experience’ . Money
(7) employed a similar construction in his 
development of ‘love maps’ for the individual. While patterns of behaviour are inﬂ  uenced by society and social forces, there is a 
dearth of evidence to show that sexual identity, orientation, or sex-ual mechanisms are also inﬂ  uenced.
Modelling normal sexual function—(i) the sex survey
One obvious way of describing normal sexual function is to ask

One obvious way of describing normal sexual function is to ask 
people what they do. Two classic sex surveys were conducted by Kinsey and his coworkers who reported the results of interviews with 12 000 males in 1948
(8) and 8000 females in 1953.(9) Their 
technique of sampling was to interview everyone in speciﬁ  c coop-
erating groups (clubs, hospital staff, universities, police force, school teachers, etc.). This gave samples of convenience but not a valid statistical sampling of the population. Despite their age and faulty sampling, however, there are still useful data in these surveys. In the sexual climate of the 1950s many of the ﬁ  ndings were regarded 
as highly controversial. Clement
(10) has reviewed the subsequent 
studies of human heterosexual behaviour up to 1990.
Surveys give a selective picture of sexual function. Results depend

Surveys give a selective picture of sexual function. Results depend 
on the formulation of the questions, they rely on self-reports, and they represent only those prepared to describe their sexual behav-iour. It is known, for example, that females tend to under-report their premarital sexual experiences
(11) while males tend to over-
report their lifetime partners.(11) Berk et al.(12) studied the recall by 
217 university students of their sexual activity over a 2-week period assessed by questionnaires answered 2 weeks after the recording period, and by daily diaries kept over the same 2 weeks. Subjects reported more sexual activity in the questionnaires than in their diaries. Women reported giving and having more oral sex than the men. Clearly, data from questionnaire surveys should be treated cautiously.

A survey tells only what is frequent and not necessarily what is 
normal, but the most frequent practices often become identiﬁ  ed
with normal sexual behaviour. Surveys also vary in the range of behaviours that are asked about, for example coitus without con-
doms is important in the age of AIDS. Surveys have one great disad-vantage, the facts that they produce are often ‘perishable’; many aspects of the sex surveys of the pre-pill era, or more recently the pre-AIDS era, are now of use only in a historical or comparative basis.
Two recent well-organized surveys based on samples of the whole 
population have been undertaken, one in the United States and the other in the United Kingdom. Interestingly, in both surveys, questions about masturbation were disliked by the respondents. In the American survey these questions were asked in a separate self-administered questionnaire, while in the British survey they were abandoned.
The American survey
(13) was conducted face to face with 3159

selected individuals who spoke English in representative house-holds by 220 trained interviewers (mainly women). Nearly 80 per cent of the individuals chosen agreed to be interviewed. Men thought about sex often, more than 50 per cent having erotic thoughts several times a day, while females thought about sex from a few times a week to a few times a month. The frequency of part-nered sex had little to do with race, religion, or education. Only three factors mattered: age, whether married or cohabiting, and how long the couple had been together. Fourteen per cent of males reported having no sex in the previous year, 16 per cent had sex a few times in the year, 40 per cent a few times a month, 26 per cent two to three times a week, and 8 per cent four times a week. The percentages were similar for women. The youngest and the oldest people had the least sex with a partner; those in their 20s had the most. Of the women aged 18 to 59 years, approximately one in three said they were

similar for women. The youngest and the oldest people had the least sex with a partner; those in their 20s had the most. Of the women aged 18 to 59 years, approximately one in three said they were uninterested in sex, and one woman in ﬁ  ve

said sex gave her no pleasure. Unlike frequency, reported sexual practices do depend on race and social class. Most practices other than vaginal coitus were not very attractive to the vast majority. In women aged 18 to 44 years of age, 80 per cent rated vaginal coitus as ‘very appealing’ and an additional 18 per cent rated it as ‘somewhat appealing’ . Among men 85 per cent regarded vaginal coitus as ‘very appealing’ . The most appealing activity second after coitus was watching the partner undress, and this was appealing to more men (50 per cent) than women (30 per cent). This reﬂ  ects the 
greater voyeuristic nature of men and their willingness to pay to look at women undressing or undressed.
In regard to oral sex, both men and women liked receiving more

In regard to oral sex, both men and women liked receiving more 
than giving. This practice varied markedly with race and educa-tion, with higher reported rates among better educated white people than among less educated and black people. Some 68 per cent of all women had given oral sex to their partner and 19 per cent experienced active oral sex the last time they had intercourse. Seventy-three per cent of all women had received oral sex from the partner, and 20 per cent had received it the last time they had had intercourse. Corresponding experiences were reported by men.
This survey, unlike many earlier ones, asked about anal sex. Of 
females aged 18 to 44, 87 per cent thought it not at all appealing, and only 1 to 4 per cent thought it very or somewhat appealing. In males 
of the same age 73 per cent thought it not at all appealing and rather

of the same age 73 per cent thought it not at all appealing and rather 
more than women thought it very or somewhat appealing. Similar reports were obtained from women and men aged 44 to 59.
Regarding masturbation, older people (over 54 years old) had 
lower rates than at any other age, indicating that they do not use masturbation to compensate for an overall decrease in sexual activity with their partners.4.11.1 normal sexual function

SECTION 4  clinical syndromes of adult psychiatry 814
In the United Kingdom survey,(14) 18 876 people were inter-
viewed by 488 interviewers (of whom 421 were women). The 
sampling used one person per address and the acceptance rate was 
71.5 per cent. Questions were asked about the frequency of vaginal 
coitus, oral sex, and anal sex, but not masturbation. The median 
number of occasions of sex with a man or woman was ﬁ  ve times a 
month for females aged 20 to 29 and males aged 25 to 34, but 
declined to a median of two per month for males aged 55 to 59. 
More than 50 per cent of the females in the 55 to 59 age group 
reported no sex in the last month, but in this age group females are 
more likely than men to have no regular partner because they are 
widowed, separated, or divorced.
Vaginal coitus was reported by nearly all females and males by 
the age of 25. Fifty-six per cent of males and 57 per cent of females 
reported vaginal coitus in the previous week, and non-penetrative

reported vaginal coitus in the previous week, and non-penetrative 
sex was practiced by 75 per cent men and 82 per cent of women. 
Twenty-ﬁ  ve per cent of males had genital stimulation in the previ-
ous 7 days. Cunnilingus and fellatio were common but less 
practiced than vaginal coitus. Of men and women aged 18 to 44, 
60 per cent had oral sex in the previous year but in the 45- to 
59-year-old group this fell to 30 per cent for women and 42 per 
cent for men. This and other sex surveys suggest that the practice of 
oral sex has increased since the 1950s and 1960s. Anal coitus was 
infrequent; approximately 14 per cent of the males and 13 per cent 
of the females had ever undertaken it, and only 7 per cent of males 
or females had practiced it in the previous year.
Modelling normal sexual function—(ii) the sexual 
response cycle
A direct way of investigating normal sexual function is to observe

A direct way of investigating normal sexual function is to observe 
and measure the body changes that take place when men and 
women become sexually aroused. From these data, models have 
been constructed of the normal sequence of changes during sexual 
arousal, coitus, and orgasm. The ﬁ  rst models described a simple 
sequence of increasing arousal and excitement culminating in rapid 
discharge by orgasm, displayed graphically as an ascent, peak, and 
then descent. As the investigations became more sophisticated, 
understanding of the body responses grew and the models became 
more detailed and complex.(5,15,16)
The EPOR model—a sexual response cycle model
A most successful human sexual response model was that formu-
lated by Masters and Johnson.(15) In the laboratory, they observed 
the changes that took place in the male and female body and

the changes that took place in the male and female body and 
especially the genitals during sexual arousal to orgasm either by 
masturbation or by natural or artiﬁ  cial coitus with a plastic penis 
that allowed internal ﬁ  lming of the female genitalia. After studying 
approximately 7500 female and 2500 male arousals to orgasm in 
some 382 female and 312 male volunteers over 11 years, they 
proposed a four-phase, sequential, and incremental model of 
the human sexual response cycle (Fig. 4.11.1.1). The phases were 
described as the excitation ( E) phase (stimuli from somatogenic or 
psychogenic sources raise sexual tensions), the plateau ( P) phase 
(sexual tensions intensiﬁ  ed), the orgasmic ( O) phase (involuntary 
pleasurable climax), and ﬁ  nally the resolution ( R) phase (dissipa-
tion of sexual tensions). The great success of this EPOR  model

tion of sexual tensions). The great success of this EPOR  model 
was its wide compass; it could characterize the sexual responses of 
women and men, both heterosexual and homosexual, ranging from simple petting to vaginal or anal coitus with or without orgasm. 
However, it had several weaknesses.
Modifying the EPOR model into the DEOR model
The ﬁ  rst weakness of the EPOR model is that it was derived from 
the study of a highly selected group of American men and women 
volunteers who could arouse themselves to orgasm in a laboratory, 
on demand, and allow themselves to be watched/filmed or 
measured for scientiﬁ  c and altruistic (or perhaps exhibitionistic) 
purposes. The second weakness was the lack of interobserver agree-
ment about the changes observed and of conﬁ  rmation of their 
sequential reliability. Robinson(16) examined the E phase and P
phase, and concluded convincingly that the P phase was simply the

phase, and concluded convincingly that the P phase was simply the 
ﬁ nal stage of the E phase. Helen Kaplan,(17) a New Y ork sex thera-
pist, proposed that before the E phase there should be a ‘desire 
phase’ ( D phase). This proposal came from her work with women 
who professed to have no desire to be sexually aroused, even by 
their usual partners. She suggested that the desire must occur 
before sexual arousal can begin. Kaplan’s subjects were attending a 
clinic and remarkably no studies were ever conducted with a 
control normal population (either women or men) to investigate 
whether this ‘self-evident’ fact was true. Despite this, the EPOR
model gradually became replaced by the desire, excitation, orgas-
mic, and resolution phase ( DEOR ) modiﬁ  cation. While this is the 
currently accepted model, the centrality of the desire phase in

currently accepted model, the centrality of the desire phase in 
women remains uncertain (Fig. 4.11.1.1). In a survey of non-clinic 
sexually experienced women in Denmark, about a third reported 
that they never experienced spontaneous sexual desire(18) and in an 
American survey women reported periods of several months
when they lacked interest in sex.(13) The other problem with
the desire phase is its location in the sequential DEOR  model. Fig. 4.11.1.1 The development of the human sexual response model from 
(a) the original EPOR  model of Masters and Johnson(15) through (b) the desire, 
excitation, orgasmic, and resolution ( DEOR ) model of Kaplan(17) to (c) the 
proposed modiﬁ  cation with desire phase 1 (before initiation of the excitation 
phase and desire phase 2 during excitation phase) and ﬁ  nally (d) with added 
courtship behaviour.

815
Sexual desire (D1-proceptive desire) that appears to be spontane-
ous (but presumably must still be activated by a trigger) should obviously be placed at the beginning of the model (Fig. 4.11.1.1b), while sexual desire (D2-receptive desire) created when theperson is sexually aroused by another occurs during the E-phase(Fig. 4.11.1.1c).
It has been proposed
(19) that while the DEOR model ﬁ  ts for 
females in younger couples’ relationships for longer maintained ones sexual activity is undertaken often for factors such as intimacy, security, and acceptance and becomes more influenced by cognitive and emotional processes and the possible outcomes of the experience (e.g. mutual pleasure, conﬁ  rming commitment 
and trust, enhancing emotional intimacy) rather than proceptive/receptive desires.
Courtship (mating) behaviour—activity 
initiating normal sexual behaviour
With the possible exception of rape, the pre-initiation of sexual

With the possible exception of rape, the pre-initiation of sexual 
activity normally starts with flirting/courtship behaviours. Sometimes this activity can precede the desire phases; sometimes it occurs during the desire phases, and sometimes in the excitation phase (Fig. 4.11.1.1d).
Evolutionary psychology attempts to explain the strategies of 
mating.
(20) Its message is not always palatable to modern sensi-
tivities about sexual equality. It is argued that women invest morein their offspring than men,
(21) that this investment is a scarce 
resource that men compete for, and that men can enhance their reproductive strategy by mating frequently. Most men are ﬁ  rst

visually attracted to a possible female sexual partner. They look for youthfulness and physical attractiveness in the form ofregular features (symmetry), smooth complexion, optimumstature, and good physique, and they value virginity and chastity. Partner variety is highly desired. Women, however, need to obtainhigh-quality mates with abundant resources and look for emo-tional and ﬁ  nancial status and security. Clearly the strategies 
conﬂ  ict giving rise to different preferences in mate choice and 
casual sex, and different levels of investment or commitment to relationships.
(22)
Once the chosen female (or male) accepts the initiation of ﬂ  irt-

(22)
ing/courtship behaviour, the subsequent stages form a stereotyped sequence which is found in many different cultures. The stages are look, approach, talk, touch, synchronize, kiss (caress), sex play, coitus. It is a sequence that the poet Ovid knew in the ﬁ  rst century 
BCE. Morris
(1) characterized human courtship behaviour further 
into 12 basic stages: eye to body, eye to eye, voice to voice, hand to hand, arm to shoulder, arm to waist, mouth to mouth, hand to head, hand to body, mouth to breast, hand to genitals, genitals to genitals. Similar hierarchies have been constructed extending the behaviour to oral-genital contacts.
Although kissing has been described as ‘an inhibited rehearsal for 
intercourse and other sexual practices’
(23) and is usually undertaken

(23) and is usually undertaken 
in the courtship behaviour well before genital activity occurs, it is sometimes thought of as more intimate than coitus. Prostitutes, for example, traditionally do not kiss their clients on the mouth, reserving the activity for their private sexual behaviour. Nicholson
(24) has speculated that kissing may be a mechanism by 
which semiochemicals (similar to pheromones) are exchanged between humans to induce bonding.Common extragenital changes during 
sexual arousal
In both males and females, effective sexually arousing stimuli 
cause a number of physiological changes.(15,25) There is increased

cause a number of physiological changes.(15,25) There is increased 
respiration, heart rate, and blood pressure, nipple erection, often sweating, and a sex flush (maculopapular skin rash). Muscle tension increases (myotonia) and the pupils dilate. All these changes become more intense as arousal increases. Following orgasm the changes dissipate rapidly (R phase); without orgasm they dissipate more slowly.
The endocrinology of normal sexual function
(a) Peptide hormones and neuropeptides

Prolactin, a peptide hormone, is secreted by cells of the anterior pituitary in both males and females. In females it is a key lactogenic hormone involved in stimulating the manufacture of breastmilk but it has no proven physiological reproductive functionin males. Pathologically high plasma levels of prolactin (hyper-prolactinaemia) are accompanied by disturbances of sexual/reproductive function especially erectile dysfunction in malesand inhibition of ovulation in females. The exact causes are unknown. As it is secreted in higher amounts at orgasm in both sexes it has been claimed to be a major factor responsible for ‘switching off’ sexual arousal but this ignores the fact that women are multiorgasmic while the evidence for this function even in males is unconvincing.
(26)
Two neuropeptides, oxytocin and vasopressin (Antidiuretic

(26)
Two neuropeptides, oxytocin and vasopressin (Antidiuretic 
Hormone, ADH) are hormones and also act as neuropeptide trans-mitters with distribution in parts of the brain and spinal cord. They are secreted as hormones by the hypothalamus/posterior pituitary with increases at orgasm in both males and females. Oxytocin is often claimed to be responsible for facilitating smooth muscle contractions during ejaculation and uterine contractions during orgasm but the possible role of vasopressin has been ignored. In some animals, oxytocin is involved in pair bonding but the evidence for this in humans is poor.
Males
(a) Androgens
The major steroids inﬂ  uencing normal sexual function in males are

Males
The major steroids inﬂ  uencing normal sexual function in males are 
the androgens secreted by the testes mainly as testosterone with much smaller quantities of androstenedione and dihydrotestoter-one. The adrenal cortex also manufactures and secretes androgens but this amounts only to 2 per cent of the total. Of the total testos-terone (260–1000 ng/dl), 95 per cent is bound to plasma proteins; only the unbound fraction (34–194 pg/ml) is an active virilizing hormone.
The development and maintenance of the masculine muscula-
ture, bone growth, genitals, and pubic and axillary hair is androgen dependent. The mechanism of the hormonal masculinization of the brain in rodents involves the aromatization of testosterone, but in humans the role of aromatization is still uncertain.
(b) Androgens and male sexual behaviour
The involvement of androgens in adult human male sexual behav-iour has been reviewed many times (see Levin
(27) for references).

(27) for references). 
Removal of testosterone by castration usually leads to a decrease in sexual activity and drive (libido) in the majority of subjects within 4.11.1 normal sexual function

SECTION 4  clinical syndromes of adult psychiatry 816
12 months. There is, however, large individual variations, and some 
castrates retain sexual activity and interest for years.(28) Factors 
such as adrenal androgens, the availability of sexual partners, and attitude to the operation inﬂ  uence the response. In castrates and in 
hypogonadal males, replacement of testosterone restores sexual interest and activity.
Females
(a) Oestrogen, progesterone, and androgens
In the female, oestrogen, progesterone, and androgens are involved in differentiating and maintaining genital and breast tissues and in inﬂ uencing normal sexual function. Female genital development, 
unlike that of the male, does not appear to need hormonal stimula-tion as the development of female genital structures are the foetal prototype or default programme.
(29) During puberty, ovarian oes-

trogen and progesterone together with androgens from the adrenal cortex induce growth and functional changes in the internal and external genitalia, breast, and nipples. Oestrogens induce growth
in the fallopian tubes, uterus, vagina, and breasts and lay down subcutaneous fat largely in the breast, hip, and thigh regions tocreate the rounded contours of the female body that are highly

in the fallopian tubes, uterus, vagina, and breasts and lay down subcutaneous fat largely in the breast, hip, and thigh regions tocreate the rounded contours of the female body that are highly 
attractive to the male. The fat laid down is enough to supply the energy for a pregnancy and the subsequent lactation. Females have a plasma androgen concentration some 10 times less (15–70 ng/dl) than those in the male. Androgens are produced by the ovaries(25 per cent), adrenals (25 per cent) and in peripheral tissuesfrom adrenal-secreted androgen precursors. They are responsible for the development and maintenance of the clitoris, nipples, pubic and axillary hair, and probably the labia, periurethral glans andpelvic-striated musculature. The variation of the androgen levelsin the plasma during the menstrual cycle is small and it is the free androgen level (1–21 pg/ml) not the bound that is the activeprinciple.
(b) Role of hormones in female sexuality

While over 60 studies have been undertaken to examine whether the changing hormonal levels of the menstrual cycle inﬂ  uence the 
sexual arousal of the female,
(30) neither oestrogen or progesterone 
have been found convincingly to play a direct role in inﬂ  uencing 
the sexual activity of the human female apart from their indirect functions in the maintenance of the structures and functions of the female genitals, especially the vagina.
The role of androgens in female sexuality is not clear-cut.
(31)
Some propose that, as in the male, it is the major hormonal inﬂ  u-
ence on the female libido. Removal of the adrenals has been shown to reduce desire and ability to reach orgasm. Excess androgens stimulates libido but in pharmacological not physiological doses. Such doses affect the structure and sensitivity of the clitoris (an androgen-sensitive tissue), so the effects on sexuality might not be only brain mediated.

(c) Sexual behaviour during the menstrual cycle
Despite numerous studies it is still uncertain whether female sexual behaviour is inﬂ  uenced by the hormonal changes in the menstrual 
cycle. Meuwissen and Over
(30) surveyed 64 published studies. 
A signiﬁ  cant number showed a premenstrual peak in sexual desire 
and activity, others a postmenstrual peak, either at menstruation or ovulation but the latter studies often used poor methodology to determine the time of ovulation.Male genital functions during normal sexual arousal
While the DEOR  model characterizes the general sexual arousal of 
humans, a more speciﬁ  c detailed physiological model in males is 
that of excitation, erection, emission, and ejaculation with orgasm. Each of these is served by separate mechanisms. Although ejacula-tion and orgasm usually occur temporally together, they also have separate mechanisms.
(a) Excitation
Sexual excitation can occur through any of the ﬁ  ve senses by psy-

chogenic or somatogenic stimuli. In special circumstances arousal can become linked to or greatly enhanced by fetishitic association with non-sexual objects such as feminine garments of underwear, rubberware, shoes, furs, etc.
The sexual excitation is manifested in the brain by activation of 
numerous areas (see section on brain activation during human sexual arousal). Centres in the spinal cord for erection and ejacula-tion are known from animal studies and it is likely that they also exist in the human cord. They are activated by neural efferent activ-ity from the aroused areas of the brain and initiate erection and ejaculation.
(b)  Erection: the conversion of the ﬂ  accid urinary penis to the 
rigid sexual penis
The three longitudinal erectile chambers of the penis are arranged

The three longitudinal erectile chambers of the penis are arranged 
with a side-by-side dorsal pair of corpora cavernosa above the single ventral corpus spongiosum. The corpora cavernosa are covered by the tunica albuginea, a 2-mm thick ﬁ  brous membrane which is 
resistant to stretch. The corpus spongiosum surrounds the length of the penile urethra and is enlarged at its base to form the urethral bulb and distally to create the glans penis. While it becomes engorged with blood during arousal it is not involved in the rigidity of the erection but protects the urethra from closure. The unaroused penis is ﬂ  accid because the pudendal arterial blood ﬂ  ow into the

erectile tissues is limited by the high sympathetic (adrenergic-mediated) constrictive tone in the smooth muscle of the vessels of corpus cavernosum. On sexual arousal, the sympathetic tone is reduced; the neural innervation of the arteries and cavernosal chambers is activated to release vasoactive intestinal peptide (VIP), 
a peptidergic vasodilator neurotransmitter that directly relaxes 
smooth muscle and nitric oxide (NO), the nitrergic neurotransmit-ter. NO activates the enzyme cyclic guanylase in the smooth muscle cells of the cavernous tissue and blood-vessel endothelium to pro-duce cyclic guanosine monophosphate (cGMP), the second mes-senger that creates intracellular conditions to relax the muscle. The enzyme phosphodiesterase 5 breaks down the cGMP and inhibi-tors of this enzyme, which can be taken by mouth, facilitate the attainment of erection even with reduced neural inputs.
The vasodilatation of the arterial supply by VIP together with the

The vasodilatation of the arterial supply by VIP together with the 
relaxation of the vessels of the cavernosal tissue allows them to ﬁ  ll 
under arterial pressure stretching the chambers until they become stiff against their covering of unyielding tunica albuginea, and the veins (emissary) that pass obliquely through the tunica become occluded greatly reducing penile vascular drainage. The ﬂ  accid 
urinary penis has been converted into the erect rigid sexual penis some 7 to 8 cm longer. The rigidity is essential for successful vagi-nal penetration and to stimulate its walls (especially the anterior) during penile thrusting. The striated muscles of the pelvic region, namely the ischiocavernosus and bulbocavernosus, are not

817
normally involved in creating penile erection(32) although they can 
be voluntarily contracted in short bursts to aid its rigidity. The engorged corpus spongiosum is less rigid than the cavernosal chambers making the glans of the penis softer and less damaging to the female labia and vagina.
(c) Internal genitals
The genital ﬂ  uids of the testes, epididymis, and accessory genital 
glands of the male are involved in emission. These glands are the bulbo-urethral (Cowper’s gland), the prostate (approximately 30 per cent of the total volume of the ejaculate), and the paired seminal vesicles (approximately 60 per cent of the volume of the ejaculate). The ﬂ  uids from all these together with that of the glands 
of Littré that line the penile urethra, constitute the ejaculate or semen which has a characteristic odour and rapidly forms a coagu-lum in contact with air. Subsequently enzymes in the semen break down the coagulum and release the trapped sperm.
(d) Emission

This phase begins with the movement of the various genital ﬂ  uids 
into the ducts initiated by the neurally induced contraction of smooth muscles in the capsules of the testes, epididymis, and seminal vesicles. The secretions spurt into the prostatic urethra, and the sphincter of the bladder neck closes to prevent reﬂ  ux into 
the bladder. When this happens the male experiences the sensation of ‘ejaculatory inevitability’ and knows that he will ejaculate within a second or two and that conscious suppression of the ejaculatory reﬂ ex is now impossible. The contractions of the smooth muscle 
of the glandular capsules together with the contraction of the vas deferens and peristalsis in the urethra move the semen along into the penile urethra.
(e) Ejaculation

Within a second or two later the bulbocavernosus muscle of the perineal region contracts clonically, initially at about 1 per 0.8 s, squeezing the urethra and forcing out the ejaculate. As ejaculation proceeds, the interval between each striated muscle contraction gets longer and their force weaker until they gradually die out.
(15,32)
Their number can vary between 5 and 60. Most of the ejaculate is expressed within the ﬁ  rst half dozen contractions. If the striated 
muscles are paralysed the semen is squeezed out only by the smooth muscle peristaltic contractions which produce a dribbling ejaculate with no projectile force and little pleasurable quality.
(f) Male orgasm

Orgasm, the supreme ecstatic pleasure is experienced just before the striated contractions occur and is then associated, throbbingly, with each subsequent contraction slowly decreasing in intensity and dying away as do the contractions. It is felt as an intense plea-surable throbbing/pumping in the penis and pelvic area and can last from 5 to 60 s. Most males groan with each squirting contraction. Kinsey et al .
(8) marshalled the evidence showing that orgasm 
and ejaculation were separate mechanisms. Brieﬂ  y, orgasm occurs 
without ejaculation in preadolescent males, in some adult males orgasm does not occur until a few seconds after ejaculation, a few adult males are anatomically incapable of ejaculation but have orgasms, and males who have been prostatectomized cannot have ejaculations but some can have orgasms.
The intensity of orgasm usually varies with the duration of

The intensity of orgasm usually varies with the duration of 
the sexual arousal (the longer it is maintained the greater the subsequent orgasm), the erotic excitement and novelty of the 
arousing stimuli, and previous ejaculation, especially the interval from the last one (initial ejaculations have usually better orgasms than subsequent ones). Males have a post ejaculation refractory time (PERT) and usually cannot have an erection or another ejacu-lation until some time has passed. The PERT varies with age and can be anything from minutes, when young, to hours or days when older.
(15) It is not known where this inhibitory mechanism resides 
but animal work suggests that it is in the brain rather than the spinal cord.
(33) Some men claim to be able to learn to inhibit ejacu-
lation and yet have repeated serial orgasms.(34)
It has been stated that the larger the ejaculate volume the greater 
is the orgasmic pleasure,(15) the studies however were flawed

is the orgasmic pleasure,(15) the studies however were flawed 
because they used men who increased semen volume by abstaining from ejaculation for days. This confounds the effects of semen volume with that of ejaculatory abstinence which itself enhances subsequent sexual pleasure. In fact semen volume does not appear to be the arbiter of pleasure or the trigger for ejaculation.
(35) Drugs 
can induce a ‘dry ejaculation’ but the pleasure of the orgasm appears unimpaired,
(33) and in young boys the pleasure of the early dry 
orgasm is not noticeably changed when semen becomes added to the ejaculation around puberty.
(36)
An ignored feature is whether there is a typology of male orgasms.

(36)
An ignored feature is whether there is a typology of male orgasms. 
Most orgasms arise from penile stimulation but they can also be activated by per rectum digital stimulation of the prostate gland. No laboratory study of these orgasms has ever been made but anec-dotal reports say that they feel deeper, more widespread and intense and last longer than those from penile stimulation.
(37)
Female genital functions during normal sexual arousal
(a) External
(i) Labia

(37)
(i) Labia
The external female genitalia consist of the outer (majora) and inner (minora) labia containing erectile tissue that surround the vaginal introitus. Normally the outer labia meet and cover the introitus, but in some women the inner labia protrude even when they are sexually unaroused. Sexual arousal creates vasocongestion especially in the labia minora which protrude through the majora adding approximately 1 to 2 cm to the length of the vagina. The labia minora become erotically sensitive to touch and friction when engorged.
(ii) Clitoris
Although the clitoris is the homologue of the penis, its precise ana-tomical structure is still uncertain. The most recent description by O’Connell et al.
(38) is of a triplanar complex of erectile tissue with a

(38) is of a triplanar complex of erectile tissue with a 
midline shaft lying in the medial sagittal plane about 2 to 4 cm long and 1 to 2 cm wide, which bifurcates internally into paired curved crura 5 to 9 cm long, and externally is capped with a glans about 20 to 30 mm long with a similar diameter. Two vaginal bulbs of erectile tissue are closely applied on either side of the urethra. The shaft’s erectile tissue consists of two corpora cavernosa surrounded by a ﬁ brous sheath (tunica albuginea) and the whole is covered by a cli-
toral hood formed in part by the fusing of the two labia minora. The uncertainty concerns the location and extent of the female corpus spongiosum. Some describe it as wrapped around the urethra, others state that the vaginal (vestibular) bulbs on either side of the vaginal wall are spongiosus tissue and unite ventrally to the urethral meatus to form a thin strand of erectile tissue ending 4.11.1 normal sexual function

SECTION 4  clinical syndromes of adult psychiatry 818
in the glans. Recent studies by van Turnhout et al.(39) have clariﬁ  ed 
the situation. They conﬁ  rmed by dissections in fresh cadavers that 
the bilateral vestibular bulbs terminate into the glans clitoridis.
With sexual arousal, the blood ﬂ  ow to the clitoris is increased 
probably by a mechanism involving its vipergic (VIP) and nitrinergic (NO) innervation leading to its tumescence (swelling) but, 
contrary to many inaccurate descriptions, without true erection (i.e. without rigidity). The enhancement of its blood ﬂ  ow is paral-
leled by an increased sensitivity to touch and friction especially of the glans.
(iii) Periurethral glans
There is a triangular area of mucous membrane that surrounds the urethral meatus, extending from just below the glans of the clitoris to the entrance of the vagina. This area has been called the ‘periure-thral glans’
(25) and is thought to be erotically stimulated, especially

(25) and is thought to be erotically stimulated, especially 
during penile thrusting, as it is known that the tissue is pushed and pulled into and out of the vagina by the penile movements.
(25) The 
periurethral glans is actually part of the corpus spongiosum if we accept the anatomical designation of van Turnhout et al.
(39) which 
suggest that it is the homologue of the male glans. The extent, mobility, density of innervation, and sensitivity of this erotic site may explain why some women ﬁ  nd it easy to reach orgasm during 
penile thrusting alone.
(b) Internal
(i) Vagina
No single structure can describe the vaginal shape. In sexual quies-cence it is a potential space with an H-shaped cross-section and an elongated S-shaped longitudinal section culminating in a cul-de-sac, the anterior wall of which is penetrated by the cervix. The anterior and posterior walls touch but their ﬁ  lm of basal vaginal ﬂ  uid 
prevents adhesion. This basal ﬂ  uid is a mixture of ﬂ  uids from the

prevents adhesion. This basal ﬂ  uid is a mixture of ﬂ  uids from the 
vagina itself (basal transudate) with uterine and cervical secretions. The squamous epithelial lining of the vagina actively transports sodium ions from the vaginal ﬂ  uid back into the blood. As ﬂ  uid 
follows this ion movement osmotically the vagina is continually producing and reabsorbing its own ﬂ  uid
(25,40) normally lower in 
sodium and higher in potassium compared to plasma.
Because sexual activity is intermittent, the basal vaginal blood 
ﬂ ow is maintained normally at a minimal level by a high adrener-

gic-mediated vasoconstrictive tone and vasomotion. The latter is the mechanism by which tissue viability is maintained at a basal level by not having all the capillaries open at the same time but rather each one opens and closes randomly to supply by demand its surrounding tissue needs of oxygen and metabolic substrates. On sexual arousal, the blood supply to the vaginal walls is increased by the liberation of VIP from the vipergic neural innervation. This increases the ﬂ  ow through the open capillaries and recruits new 
ones until all are open and vasomotion disappears,
(41) Within 
seconds this creates blood-vessel engorgement and an increased plasma transudate ﬁ  lters out of the capillaries and percolates

seconds this creates blood-vessel engorgement and an increased plasma transudate ﬁ  lters out of the capillaries and percolates 
between the cells of the epithelium saturating its limited reabsorp-tive capacity. The newly formed neurogenic vaginal transudate, with its higher sodium ion concentration, creates a lubricating ﬁ  lm 
on the vaginal surface which is essential for painless penile penetra-tion and thrusting. Poor or inadequate lubrication can lead to dyspareunia (painful coitus) and subsequent sexual dysfunction. On cessation of sexual arousal or after orgasm the blood ﬂ  ow returns to the basal level, the ﬂ  uid is reabsorbed back into the blood 
following the continuous absorption of sodium ions by the vaginal epithelium and vasomotion is restored.
(ii) Coitus and the vagina

The cul-de-sac of the vagina is expanded during sexual arousal and the uterus with cervix is lifted clear of its posterior wall (vaginal tenting).
(15) This vaginal tenting is an important reproductive 
feature that delays the transport of sperm allowing the ejaculate to decoagulate and initiate motility and pre-capacitation changes that facilitate the process of sperm capacitation (see Levin
(40,41) for 
references). In the ventral–ventral (‘missionary’) coital position,

references). In the ventral–ventral (‘missionary’) coital position, 
penile penetration and thrusting stretches and stimulates the structures of the anterior vaginal wall which include the urethra, the ‘G spot’ (see below), and neural structures in Halban’s fascia. All these (the anterior wall erotic complex) are thought to be capable of creating erotic excitement when so stimulated, giving rise to a signiﬁ  cant part of the sexual pleasure normally experienced by 
most women during coitus.
(iii)  The erotic structures of the anterior vaginal wall: urethra, 
‘G spot’, and Halban’s fascia
The urethra, approximately 4 cm long, is invested with erectile 
tissue which becomes engorged on sexual arousal. Ultrasound imaging during coitus has shown that the thrusting penis stretches the urethra.
(42) There is an area on the anterior vaginal wall a few

(42) There is an area on the anterior vaginal wall a few 
centimeters from the introitus, at or around the junction of the urethra with the bladder, that becomes swollen and on strong pres-sure stimulation can induce orgasm. This urethral area was ﬁ  rst 
identiﬁ  ed by Grafenberg
(43) but the observation was overlooked 
until its rediscovery by Perry and Whipple(44) who named it the 
‘G spot’ in recognition of the original discoverer. Anatomically, it probably represents the ‘paraurethral’ or ‘periurethral’ glands now referred to as the ‘female prostate’ . In some women these produce at orgasm a small amount of ﬂ  uid secretion loosely 
referred to as the ‘female ejaculate’ (see
(25,44) for references). These 
glands are in the space between the bladder trigone and the neck of the urethra which is ﬁ  lled with ﬁ  broelastic mesenchymal lamina

glands are in the space between the bladder trigone and the neck of the urethra which is ﬁ  lled with ﬁ  broelastic mesenchymal lamina 
rich in vascular lacunae and contains nerve ﬁ  bres and pseudocor-
puscular terminals. This area, known as Halban’s fascia
(45) when 
stimulated by pressure (penile or digital) creates intense sexual pleasurable feelings.
(44–46) As any pressure stimulus on the anterior 
vaginal wall will in fact stimulate the G spot, Halban’s fascia and the urethra at the same time it makes it difﬁ  cult to apportion the 
generation of sexual pleasure to any speciﬁ  c structure.
The involvement of the spinal cord in activating the female 
erotic structures during sexual arousal has been poorly studied and little is known of possible mechanisms.
(c) Female orgasm

As in the male, the female orgasm creates supreme ecstatic pleasure usually accompanied by throbbing striated muscle contractions, especially of the ischiocavernous and bulbospongiosus muscles, but other pelvic-striated muscles can also be involved.
(15,37)  Most 
females groan or moan during these contractions. The induction of orgasm in women by coital stimulation alone is not as frequent as that in the male, about half not achieving orgasm unless clitoral stimulation is also used. The reason for this difference is usually ascribed either to the greater inhibitory education about sexual pleasure experienced by women or the lack of correct genital

819
stimulation. A major difference between males and females is that 
females can be multiorgasmic because they do not have a PERT after orgasm.
(15,23,33) There is mounting evidence that, unlike the 
unitary concept of the DEOR  model, the erotic stimulation of dif-
ferent genital sites (especially the anterior vaginal wall compared with the clitoris) induces different types of orgasmic response both subjectively and physiologically.
(44,47,48)
Brain activation during human sexual arousal
Before the advent of brain imaging by functional magnetic reso-nance imaging (fMRI) or positron emission tomography (PET) to identify which areas are activated by and during sexual arousal and orgasm, only limited information was obtained by observing the effects of brain lesions on behaviour, epileptic case studies, electroencephalography (EEG) activity, and rare electrical record-ings and stimulations of speciﬁ  c brain areas.
(27) Inferences about

(27) Inferences about 
human sexual arousal mechanisms often had to be made from animal experiments but the problem of species differences always was the spectre in the wings (see comment below).
One type of brain imaging (blood oxygen level dependent 
[BOLD]) relies on the concept that activation of neurones requires an increased demand for oxygen which normally entails an increase in their blood supply bringing oxygenated blood. The change in the magnetic susceptibilities of the oxygenated and deoxygenated blood is measured and is an index of the increase or decrease in ﬂ ow to the neuronal area. In the PET technique a short-lived 
radioactive tracer (often 
15O) is injected intravenously and its 
concentration in the brain area of high blood ﬂ  ow localized by the

concentration in the brain area of high blood ﬂ  ow localized by the 
radioactivity. Both techniques rely heavily on extensive computer programs to correct for a variety of essential artefact corrections one of the most important being corrections for movement. The usual protocol underlying most studies of sexual arousal is to ﬁ  rst 
measure the activity of the brain area under study during a non-sexual basal state (looking at neutral videos) then switching to viewing sexually arousing videos. By subtracting the activity of the neutral from the aroused measurements the remaining activity is assumed to be due the sexual arousal per se. One difﬁ  culty is what 
level (threshold) of activity of a site is to be regarded as physiologi-cal. Investigators tend to choose their own criteria making direct comparisons between different studies difﬁ  cult. Another difﬁ  culty

is that many areas of the brain are multifunctional (e.g. the amyg dala, 
the periaqueductal grey, the cerebellum) and are thus activated/deactivated by different stimuli (viz., pain, pleasure, fear, anger, emotional processing) the activation/deactivation may be an epi-phenomenon of the arousal rather than its cause. Finally, it takes a few seconds to build up a brain scan but neuronal activation takes just hundredths of a second; the image will always lag behind the actual activation so that identifying what is the primary initiator of brain arousal will not be apparent.
Despite all the above caveats about brain imaging one outstanding

Despite all the above caveats about brain imaging one outstanding 
conclusion is now clear from all the various studies—that there does not appear to be a single site creating arousal or orgasm, multiple site co-activation (also referred to as a neural network) is the rule in both males and females. While a number of the features of brain activa-tion appear common to sexual arousal in the brains of both sexes, the amygdala and hypothalamus are said to be more strongly activated in men when viewing identical sexual stimuli. According to Holstege’s group,
(47) the ﬁ  rst to map brain areas active during ejaculation/orgasm, the strongest activated primary region during male erec-
tion/orgasm is the ventral tegmental ﬁ  eld region, the midbrain lat-
eral central tegmental ﬁ  eld, the zona incerta, the suprafascicular

eral central tegmental ﬁ  eld, the zona incerta, the suprafascicular 
nucleus, the ventroposterior, midline and intralaminar nucleus, and the cerebellum. Decreased activity was seen in the amygdala and adjacent entorhinal cortex. This decrease in the amygdala is said not to occur during women’s arousal.
(48) Another group.(49) imaging the 
brain in sexually aroused males reported increased neural activity in areas that included the right frontal cortex, the inferior temporal cor-tex, the left anterior cingulate cortex, and the right insula. However, only a subset of these areas (anterior cingulate, insula, amygdala, hypothalamus, and secondary somatosensory cortex) were involved in creating a full erection.
Imaging studies undertaken by Komisaruk and Whipple
(48) used

(48) used 
both women who were paraplegic and some able-bodied women who had the rare ability to create orgasm by mental activity (thoughts) alone. In the former group, where arousal was induced by cervical vibratory stimulation, a large number of sites, including the hypothalamus, were activated by the stimulus used to induce orgasm but in the mental activity group, the only sites activated by thought were regions of the nucleus accumbens, the paraventricular nucleus of the hypothalamus, the hippocampus, and anterior cingu-late cortex. The authors suggested that these sites may be speciﬁ  cally 
related to activate the female orgasm. Interestingly, the amygdala was not activated during these ‘thought’ induced orgasms. How ‘normal’ the ‘orgasm by thought’ group are is yet to be ascertained.
It is unfortunate that while there are now a number of indepen-

dent studies on brain imaging during sexual arousal the resultant descriptions of the areas claimed to be the activated or deactivated are not in agreement. Part of the problem is that different stimuli, duration of stimuli, data handling, and processing protocols have 
been used but even these do not explain all the differences. Thus, 
at present, it is not possible to give a detailed and reliable account of brain activation during sexual arousal.
Summary
Normal human sexual function can be characterized simply by its biological mechanisms which are of obvious importance, not least to reproduction.
(41) The mechanisms have changed little over the

(41) The mechanisms have changed little over the 
centuries, but their expression as behaviour, when moulded by historical time, social class, ethnic grouping, religion, and society, creates the changing complex concept of human sexuality. Indeed, it has been said that human sexuality is more about fertilizing relationships than eggs! While we have increased hugely our knowledge about many of the mechanisms involved in human sex-uality, the impact of a highly successful oral therapy for erectile dysfunction being an obvious example, those of the brain and spinal cord are practically unexplored. What creates human sexual desire and sexual excitement and what causes them to fade away, where in the brain is the pleasure of orgasms created, why do men have a PERT but not women, are just a few of the fascinating questions that remain to be answered.
Goldstein, I., Meston, C.M., Davis, S.R., et al. (eds.) (2006). Women’s sexual

Goldstein, I., Meston, C.M., Davis, S.R., et al. (eds.) (2006). Women’s sexual 
function and dysfunction: study, diagnosis and treatment . Taylor & 
Francis, London.4.11.1 normal sexual function

SECTION 4  clinical syndromes of adult psychiatry 820
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Press, Bloomington, IN.
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Komisaruk, B.R., Beyer-Flores, C., and Whipple, B. (2006). The science of 
orgasm . The Johns Hopkins University Press, Baltimore, MD.
Lue, T.F., Basson, R., Rosen, R., et al. (eds.) (2004). Sexual medicine- sexual 
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821
4.11.2 The sexual dysfunctions
Sexual relationships are central to the lives of most of us. The 
sexual component of those relationships can go wrong in various ways. This may be secondary to other difﬁ  culties in the relation-
ship, mental health problems, speciﬁ  c sexual vulnerabilities of 
the individual, or the impact of disease or medication on sexual response. This chapter will describe the more common sexual problems and their prevalence. Evidence related to aetiology of sexual problems and treatment evaluation will be brieﬂ  y reviewed. 
In the ﬁ  nal section of the chapter, guidelines for the assessment and 
practical management of sexual problems will be presented.
Historical aspects and some basic concepts
Since 1970, when Masters and Johnson(1) published their ground-
breaking book on the treatment of ‘human sexual inadequacy’ , there have been two lines of development in this ﬁ  eld, relatively

breaking book on the treatment of ‘human sexual inadequacy’ , there have been two lines of development in this ﬁ  eld, relatively 
detached from each other until recently: psychological methods of treatment, collectively known as ‘sex therapy’ and medical inter-ventions, initially focused on erectile problems in men.
The involvement of the medical profession has been substan-
tial, although predominantly involving urologists. Initially there were surgical procedures to implant penile splints or to improve the vascular supply to the penis, and the use of vacuum devices to induce erection mechanically. This was followed by the discovery that injection of smooth muscle relaxants, such as papaverine, phentolamine, or prostaglandin into the erectile tissues ofthe corpora cavernosa induced erections. Self-injections became widely prescribed. T o avoid the need for penile injections, which

were not popular among male patients, preparations of prosta-
glandin for intra-urethral administration became available. This era of medical intervention was characterized by a veritable industry of investigative procedures in attempts to identify local causes for erectile dysfunction (ED). Erectile problems were clearly differentiated into ‘organic’ and ‘psychogenic’ subtypes. There was, however, a notable lack of attention to how the brain and psychological processes interacted with these peripheral mechanisms.
Then came the ‘Viagra revolution’ in the early 1990s. The ﬁ  rst 
oral phosphodiesterase 5 (PDE-5) inhibitor, sildenaﬁ  l (Viagra ®),

oral phosphodiesterase 5 (PDE-5) inhibitor, sildenaﬁ  l (Viagra ®), 
was found to be effective in enhancing erectile response to sexual stimulation when taken about 1 h before sexual activity. This led to the next phase in the ‘medicalization’ of male sexual dysfunction, with a shift to the primary care physician as the principle source of treatment and a dramatic reduction in the amount of diagnostic assessment.
The progress of sex therapy has been limited since Masters and 
Johnson.
(1) It has continued to be used, with various adaptations of 
the original ‘sensate focus’ approach, incorporating principles of psychoanalytic techniques
(2) and cognitive behaviour therapy.(3)
The main shortcoming has been inadequate outcome research on the efﬁ  cacy of these methods.The next phase in this recent history followed the commercial

The main shortcoming has been inadequate outcome research on the efﬁ  cacy of these methods.The next phase in this recent history followed the commercial 
success of PDE-5 inhibitors for men, with an inevitable quest for a ‘Viagra for women’ . This has so far proved elusive, but has con-fronted the ‘sexual medicine’ community with the complexity of women’s sexuality and the need to conceptualize it differently to the sexuality of men.
At the same time, evidence has emerged that treatment of ED 
with sildenaﬁ  l and more recent PDE-5 inhibitors, although initially 
successful in the majority, was being discontinued by a substantial proportion of men.
(4) In addition, the female partners of men tak-
ing these drugs do not always welcome the associated changes in the sexual relationships.
(5) We are now moving into the most recent

(5) We are now moving into the most recent 
phase where the ‘psychological’ and ‘organic’ approaches, and the professional groups that have been identiﬁ  ed with them, have 
started to interact. There is increasing recognition of the need to integrate psychological and medical methods of treatment,
(6,7) but 
with the important proviso that, at least initially, treatment should focus on the couple and not the individual.
One important aspect of this evolving story is how we deﬁ  ne a 
‘sexual dysfunction’ , with connotations of abnormal or impaired function, and how it is distinguished from a ‘sexual problem’ in a more general sense. This issue was epitomized by a publication in theJournal of the American Medical Association  on the epidemiolo-
gy of ‘sexual dysfunction’ .
(8) In this widely cited paper, 43 per cent

(8) In this widely cited paper, 43 per cent 
of women and 31 per cent of men were identiﬁ  ed as having a 
‘sexual dysfunction’ , described as ‘a largely uninvestigated yet sig-niﬁ cant public health problem’ (p. 544). The authors commented, 
‘With the affected population rarely receiving medical therapy for sexual dysfunction, service delivery efforts should be augmented to target high-risk populations’(p. 544).
This dramatic example of ‘medicalization’ , based on extremely 
limited information from a national survey not designed to assess sexual dysfunction, was effectively challenged by Mercer and col-
leagues, using data from the UK National Survey of Sexual Attitudes and Lifestyles (NATSAL).
(9) This used exactly the same questions 
as in the Laumann et al . study,(8) with the important difference 
that it was more speciﬁ  c about duration of problems, asking

that it was more speciﬁ  c about duration of problems, asking 
whether particular problems had lasted ‘at least 1 month’ , or ‘at least 6 months’ during the last year (Laumann et al. had asked if symp-
toms had occurred ‘for several months or more’ during the last year). Overall, 53.8 per cent of women and 34.8 per cent of men reported at least one sexual problem lasting at least 1 month during 
the previous year. In contrast, the prevalence of problems lasting 
‘at least 6 months in the previous year’ was 15.6 per cent for women and 6.2 per cent for men. This showed that transient problems were very common, more persistent ones much less so. In both the American and the British study, such problems were related to other problems in the participants’ lives, particularly involving impaired mental health (e.g. depression), relationship problems, or signiﬁ  cant life stresses.

Relevant to the question of when a sexual problem becomes a 
‘dysfunction’ is a theoretical approach, called the ‘Dual Control 
Model’ , developed at the Kinsey Institute. This postulates that sexual response results from an interaction between excitation and 
inhibition, involving relatively discrete neurophysiological systems 
in the brain.
(10) A central assumption of the model is that individu-
als vary in their propensity for both sexual excitation and sexual 
inhibition and that ‘normal’ levels of inhibition are adaptive, 
reducing sexual responsiveness in circumstances where sexual 4.11.2 the sexual dysfunctions

SECTION 4  clinical syndromes of adult psychiatry 822
activity is best avoided. It is predicted that high levels of inhibition 
may be associated with vulnerability to sexual dysfunction and low levels with an increased likelihood of engaging in high-risk sexual behaviour.
(10)
This faces us with the seemingly obvious but fundamental 
challenge of deciding whether a loss of sexual interest or respon-siveness is an understandable or even adaptive reaction to current circumstances, or is a result of ‘malfunction’ of the sexual response system, which can appropriately be called a ‘sexual dysfunction’ . This challenge is also central to the relatively new phase of inte-grated treatment, in which assessment identiﬁ  es the key factors 
causing the sexual problem and how they should best be treated. A strategy for carrying out such assessment, which we have called the ‘three windows approach’ , will be outlined below.
Clinical features of sexual problems
Sexual problems in men

The most common problems presented by men are ED and prema-ture ejaculation (PE). Delayed or absent ejaculation is a relatively infrequent complaint. Low sexual desire may be the presenting problem, although in most cases this is combined with ED, and it is not always clear which came ﬁ  rst.
(a) Erectile problems
Penile erection is a tangible and fundamental component of a 
man’s experience of sexual arousal and the lack of erection ina sexual situation often has signiﬁ  cant negative effects. Irrespective 
of whether or not there are peripheral explanations for impaired erections (e.g. vascular disease), the reactions of the man andhis partner have a major inﬂ  uence on how problematic the
erectile difﬁ  culty becomes. Erectile difﬁ  culties vary in severity;
in some men the problem only occurs on a proportion ofoccasions of sexual activity. The difﬁ  culty may be in getting an

in some men the problem only occurs on a proportion ofoccasions of sexual activity. The difﬁ  culty may be in getting an 
erection or in maintaining it long enough for satisfactory sexual intercourse.
(b) Low sexual desire
For many men, sexual desire is linked with erectile responsiveness. Many men with low sexual desire also report a reduction in ‘spontaneous’ erections. However, a man can experience low sexual desire without having any erectile difﬁ  culties, although he may 
require more direct tactile stimulation to achieve erections.
(c) Premature ejaculation (PE)

Ejaculation results from a combination of orgasm and seminal emission, with muscular contractions as part of the orgasmic response resulting in expulsion of the seminal emission. PE is essentially a problem when the man is unable to delay orgasm and ejaculation as he would wish. Not surprisingly, this has led to considerable inconsistencies of deﬁ  nition in the literature. In severe 
cases, emission occurs before vaginal entry and the orgasmic component may be so reduced that the usual muscle spasms do not occur, resulting in semen seeping out of the urethra rather than being ‘ejaculated’ .
Premature ejaculation has been categorized as ‘primary’ (i.e. life-

long) or ‘secondary’ . Secondary PE is often confounded by erectile problems. If a man is taking a long time to get an erection, he may reach the stimulus intensity required for ejaculation before or soon after erection is achieved.(d) Delayed ejaculation
Delayed or absent ejaculation occurs in men, although it is much less common than rapid ejaculation. A man might have difﬁ  culty 
ejaculating only during sexual activity with his partner and in some cases only during penetrative intercourse, or the problem may be evident even during masturbation. Delayed or absent ejaculation is a common side effect of selective serotonin re-uptake inhibitor (SSRI) medications, which often prevents orgasm in women as well, suggesting that the primary effect of such drugs is on the triggering of orgasm.
(e) Pain during sexual response

Pain may be associated with prolonged sexual arousal not termi-nated by ejaculation/orgasm. Such pain is usually experienced in the testes. Pain felt in the urethra may occur during ejaculation. Neither problem is common.
Sexual problems in women
(a) Loss of sexual arousal and/or desire
Most surveys have suggested that low sexual desire is the most com-mon sexual problem reported by women. However, low sexual desire is a heterogeneous problem category and the relationship between sexual arousal and sexual desire in women is particularly complex. Many women do not differentiate between ‘arousal’ and ‘desire’
(11) and awareness of ‘desire’ is usually accompanied by some 
degree of central arousal, whether or not any genital response is perceived.
(12) It has been argued that sexual desire in women is 
much more likely to be ‘receptive’ and triggered by a desire for intimacy with one’s partner.
(13) It is therefore not surprising that

(13) It is therefore not surprising that 
there is considerable overlap or comorbidity between problems related to sexual arousal and desire in women.
(8)
Although traditionally seen as the counterpart to penile erection 
in men, vaginal response is not central to the experience of sexual arousal in women. Vaginal dryness may be a problem because of the likelihood of discomfort or pain with intercourse when the vagina is not adequately lubricated, but this symptom does not necessarily indicate lack of arousal. Conversely, a woman may expe-rience lack of sexual arousal and yet have vaginal lubrication. The relevance of vaginal response to sexual arousal in women therefore remains unclear. An increase in vaginal blood ﬂ  ow has been consis-
tently demonstrated in women reacting to sexual stimuli, whether

tently demonstrated in women reacting to sexual stimuli, whether 
or not they ﬁ  nd the sexual stimulus appealing; this led Laan 
and Everaerd
(12) to call this an ‘automatic’ response. There is no 
obvious counterpart to this in men. Tumescence of the clitoris, on the other hand, may be more directly comparable to male genital response but this is less easily assessed and less clearly perceived by women, compared with penile erection in men.
Persistent genital arousal disorder (PGAD) is a recently recog-
nized but fairly uncommon sexual problem in women. It is charac-terized by genital and breast vasocongestion and sensitivity which persists for hours or days and is only temporarily relieved by orgasm; genital sensations are unaccompanied by any subjective sense of sexual desire and excitement but instead are perceived as intrusive. There is no male equivalent to this problem, probably 
because the post-orgasmic refractory period is more substantial 
in men.

in men.
Much less frequent than loss of sexual arousal or desire is extreme 
aversion to, and avoidance of all sexual contact with, a sexual 
partner. This can occur in women and in men.

823
(b) Problems with orgasm
Difﬁ culty in achieving orgasm is not uncommon in women. Often 
this is situational in that orgasm is possible with masturbation,but not during sexual interaction with the partner. The capacityto experience orgasm varies considerably across women. Some women reach orgasm easily if sufﬁ  cient arousal occurs, others
may require more speciﬁ  c or more intense stimulation, and an
estimated 10–15 per cent are unable to experience orgasm through-out their lives.
(14) In identifying a problem as primarily orgasmic, 
one needs to ﬁ  rst establish that appropriate sexual arousal has 
occurred.
(c) Problems with sexual pain and vaginismus
Pain during attempted or complete vaginal entry (dyspareunia) is a common sexual problem in women with a wide range of possible causes. Sexual pain is also frequently associated with lack of sexual desire and/or arousal. Vaginismus has traditionally been deﬁ  ned

as recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that makes vaginal penetration difﬁ cult or impossible. This deﬁ  nition has recently been questioned 
because of a lack of empirical evidence that vaginal spasms occur in women diagnosed with vaginismus.
(15) Vulvar vestibulitis 
syndrome (VVS) is a condition associated with pain on touching the labia or vaginal introitus. The question of whether these are primarily ‘sexual’ or pain disorders is currently under debate.
(16)
Classiﬁ  cation of sexual problems
DSM-IV and ICD classiﬁ  cation
The current Diagnostic and Statistical Manual of Mental Disorders 
(DSM) classiﬁ  cation(17) deﬁ nes sexual dysfunction as characterized 
by ‘disturbance in sexual desire and in the psychophysiological changes that characterize the sexual response cycle and cause marked distress and interpersonal difﬁ  culty’ (p. 493). There is

by ‘disturbance in sexual desire and in the psychophysiological changes that characterize the sexual response cycle and cause marked distress and interpersonal difﬁ  culty’ (p. 493). There is 
Hypoactive Sexual Desire Disorder and Sexual Aversion Disorder, deﬁ ned in the same way for men and women. Female Sexual 
Arousal Disorder is deﬁ  ned as ‘a persistent or recurrent inability 
to attain, or to maintain until completion of the sexual activity, an adequate lubrication-swelling response of sexual excitement’ (p. 502) and, for the male version, erection is the relevant response. Orgasmic Disorder (i.e. delayed or absent orgasm) and Dyspareunia are defined in basically the same way for men and women. Vaginismus is a specifically female diagnosis and Premature Ejaculation an exclusively male disorder.
The International Statistical Classification of Diseases and 
Related Health Problems
(18) covers sexual dysfunctions in one and

(18) covers sexual dysfunctions in one and 
a half pages, compared with nearly 30 pages in the DSM. The basic categories of dysfunction are similar to those of DSM, but there are few, if any, actual diagnostic criteria given for any of the dys-functions. ICD-10 also does not require that personal distress or interpersonal problems are present for a diagnosis to be made. Instead, there is the statement ‘sexual dysfunction covers the vari-ous ways in which an individual is unable to participate in a sexual relationship as he or she would wish’ (p. 355).
There has been increasing dissatisfaction with the current classi-
ﬁ cation of sexual dysfunction for women.
(19,20) . Major areas of

(19,20) . Major areas of 
criticism include the high comorbidity between diagnoses of sexual dysfunction and the ‘genital’ focus of the diagnostic criteria and concomitant neglect of psychological and relationship factors. In response, alternative models of sexual response
(13) and women-
centred deﬁ  nitions of sexual problems(21) have been proposed.
There have been at least 12 representative community-based 
surveys that have assessed the prevalence of sexual problems.(22)
Prevalence rates for speciﬁ  c problems vary considerably and where-
as several of the studies claim to be reporting prevalence of sexual ‘dysfunctions’ ,
(8) it is now accepted that the detailed clinical assess-
ment required to identify a sexual dysfunction cannot be under-taken by large-scale surveys.
(23) Consequently, more recent surveys

(23) Consequently, more recent surveys 
have used terms such as ‘problems’(9,24) or ‘difﬁ  culties’ .(25) Variability 
in reported prevalence rates can in part be attributed to variations in how sexual problems are deﬁ  ned, their duration, and how and 
whether ‘distress’ about changes in sexual functioning is assessed. In studies of female sexual problems, there has been only limited overlap between what women perceive as problematic and what the researcher or clinician identiﬁ  es as a problem.
(26,27)  The variability 
of prevalence rates is shown in Tables 4.11.2.1 and 4.11.2.2, which compare a number of population-based surveys involving women and men.
There has been more consistency across studies in the associa-

tions found between factors of possible aetiological relevance and sexual functioning. In women, sexual problems are more frequent in those with mental health problems and relationship difﬁ culties.
(8) In a survey of women aged 20–65 years, all in hetero-
sexual relationships, 24.4 per cent reported marked distress about their sexual relationship and/or their own sexuality.
(26) The best 
predictors of distress were markers of mental health and the quality of the emotional relationship with the partner. Physical aspects of sexual response in women such as arousal and orgasm were poor predictors of distress.
In men, age has a predictable negative effect on erectile function. 
In one study, complete erectile failure was reported by 5 per cent of men at age 40 and 25 per cent at age 70.
(28) A similar age effect is

(28) A similar age effect is 
found with loss of sexual desire. In another study, absence of any sexual desire was reported by 2 per cent of men aged 45–59 and 18.2 per cent aged 75+.
(29) Contrary to popular belief, PE does not 
show a clear negative relationship with age.
The association between age and sexual problems in women is 
more complex. Whereas level of sexual interest typically decreases with age, older women are less likely to regard this as a problem.
(26)
Older women are much less likely to be in a sexual relationship than older men; the presence or absence of a partner also seems to inﬂ uence women’s sexuality to a greater extent than it does for 
men.
(29) The impact of the menopause is also complex. Although

men.
(29) The impact of the menopause is also complex. Although 
the post-menopausal decline in oestrogens is relevant to vaginal lubrication, other factors such as mental health and the quality of the sexual relationship are more important determinants of sexual well-being.
(30)
Aetiology
Before considering the factors that can cause sexual problems, it is worth underlining the important way that sexual function differs from most other physiological response systems. Although involv-ing physiological mechanisms, sexual responses are most often experienced in the context of a relationship. This highlights the 4.11.2 the sexual dysfunctions

SECTION 4  clinical syndromes of adult psychiatry 824
importance of keeping the interactive relationship components 
in mind when trying to assess and treat sexual problems. Socio-cul-tural factors are also crucial to understanding how sexual problems are experienced. Much of the focus in medical treatments of sexual problems has been on the individual patient, with relationship and socio-cultural aspects largely ignored. The more speciﬁ  c aetiologi-
cal factors can now be considered using the ‘three windows approach’ .
(26)
The ﬁ  rst window—the current situation
Through the ﬁ  rst window, a variety of factors in the individual’s 
current relationship and situation may be relevant. Relationship problems, particularly resentment and insecurity within a relation-ship, are of particular importance. For many individuals, feeling secure and being able to ‘let go’ are necessary for them to enjoy sex.

Other factors that may be important include: poor communication between partners about their sexual feelings and needs; misunder-standings and lack of information; unsuitable circumstances and lack of time e.g. fatigue, lack of privacy, and work pressures; con-cerns about pregnancy or about sexually transmitted diseases; and low self-esteem and poor body image.
Various mechanisms may mediate the effects of the above 
situational factors on sexual functioning. Reactive inhibition, as postulated by the Dual Control Model,
(10) may well be involved in 
those circumstances associated with a negative emotional response. With stress and fatigue, the mechanisms are less clear, but may entail a transient reduction in the capacity for excitation (i.e. sexual arousability).Table 4.11.2 .1 Prevalence of speciﬁ  c female problems (%) found in seven community-based surveys
Study Low sexual 
interestImpaired 
arousalImpaired 
lubricationImpaired orgasm Pain Total (one or more 
problems)

problems)
Richters et al. (2003)(25)1
 At least 1 month 54.8 – 23.9 28.6 20.3
Mercer et al. (2003)(9)1
 At least 1 month 40.6 – 9.2 14.4 11.8 53.8
 At least 6 months 10.2 – 2.6 3.7 3.4 15.6Bancroft et al. (2003)
(26)37.2 12.2 31.2 9.3 3.3 45
Laumann et al. (1999)(8)131.6 – 20.6 25.7 15.5 43a
Fugl-Meyer and Fugl-Meyer (1999)(59)133.0 – 12.0 22.0 6.0 47
Dunn et al. (1999)(24)2– 17.0 28.0 27.0 18.0 41
Osborne et al. (1988)(37)217.0 – 17.0 16.0 8.0 33
a Includes additional problem categories not shown in this table.
1 During last year.
2 During last 3 months.
3 During last month.
Table 4.11 .2.2 Prevalence of speciﬁ  c male problems (%) found in ﬁ  ve community-based surveys
Study Low sexual interest Erectile problem Premature 
ejaculationDelayed 
ejaculationTotal (one or 
more problems)
 At least 1 month 24.9 9.5 23.8 6.3 –

 At least 1 month 17.1 5.8 11.7 5.3 34.8
 At least 6 months 1.8 0.8 2.9 0.7 6.2Laumann et al. (1999)
(8)114.6 10.2 30.6 7.8 31.0a
Fugl-Meyer and Fugl- Meyer (1999)(59)116.0 5.0 9.0 – –
Dunn et al. (1999)(24)2– 26.0 14.0 – –

825
The second window—vulnerability of the individual
Although a wide range of factors can impact on our sexuality, it is 
also clear that individuals vary substantially in the extent to which they are affected by such factors, particularly in terms of an associated inhibition of sexual response. Such vulnerabilities are likely to have been evident in earlier episodes in the current relationship or in earlier relationships.
(a) Negative attitudes
Long-standing attitudes, usually stemming from childhood, that sex is inherently ‘bad’ or immoral are likely to interfere with an individual’s ability to become involved in and enjoy a sexual relationship.
(b) Need to maintain self-control
In some individuals, a difﬁ  culty in ‘letting go’ sexually reﬂ  ects a 
more general need to maintain self-control, particularly in the presence of another person.
(c) Earlier experience of sexual abuse or trauma

There is now an extensive literature on the impact of sexual abuse on subsequent sexual adjustment. Whereas the mediating mecha-nisms are not well understood and are likely to be complex and varied, a history of such experience should be regarded as poten-tially relevant to current sexual difﬁ  culties.
(d) Propensity to sexual inhibition
The Dual Control Model, discussed earlier, has led to psychometri-
cally validated measures of propensity to sexual excitation and inhibition in men
(31) and women.(32) These are new measures and 
research exploring their relevance to vulnerability to sexual problems has only recently started. However, using these measures, close to normal distributions of scores for both sexual excitation and inhibition proneness have been reported in men
(31) and

(31) and 
women.(32) As predicted, a clear association between low sexual 
excitation and/or high sexual inhibition propensity and erectile problems in men has been found, but no association with PE.
(33)
One study explored a possible genetic basis for such individual variability in men and found evidence of heritability for propensity to sexual inhibition but not excitation.
(34) In women, a strong rela-
tionship between sexual inhibition scores and reports of sexual problems was found.
(35) Particularly important was one inhibition 
subscale (labelled ‘arousal contingency’) that reﬂ  ects susceptibility

subscale (labelled ‘arousal contingency’) that reﬂ  ects susceptibility 
for sexual arousal to be easily affected by situational factors e.g. if the circumstances are not ‘just right’ or if the woman is distracted. Although further research is needed, these measures of sexual inhi-bition and excitation may prove valuable in explaining patterns of impaired sexual response and helping in the selection of appropri-ate treatment. As yet no other personality-related or trait measure has been shown to have clinical value in this respect.
The third window—health-related factors that alter 
sexual function
The variety of health-related factors are considered under three 
headings: mental health, physical health, and sexual side effects of medication.
(a) Mental health and sexuality
Psychiatric problems are commonly associated with sexual problems.

(36,37) Reduction in sexual interest, and to some extent sexual arousability, is generally accepted as a common symptom of 
depressive illness.(38) In contrast, sexual interest tends to be 
increased in states of elevated mood such as hypomania.(39) In a 
study of men and women with primary loss of sexual interest, the large majority had experienced previous affective disorder, with reduced sexual desire being established during, and persisting after, one of these earlier depressive episodes.
(40)
We would expect reactive inhibition of sexual interest or response

(40)
We would expect reactive inhibition of sexual interest or response 
in circumstances eliciting negative mood (i.e. ‘reactive depression’). With more endogenous depression, however, reduction of the excitatory component of sexual response is also evident. This is shown clearly in the impairment of nocturnal penile tumescence (NPT) that typically occurs with depressive illness. NPT, while not completely understood, probably results from a ‘switching off’ of inhibitory tone during REM sleep. This therefore allows expression of ‘excitatory tone’ , presumably impaired in depression with associ-ated metabolic changes.
With anxiety, the clinical evidence is much more limited. Higher 
rates of sexual dysfunction in patients with anxiety disorders have been reported.
(41) In the Zurich Cohort Study, a longitudinal study

(41) In the Zurich Cohort Study, a longitudinal study 
of men and women aged 20–35 years, loss of sexual interest was more prevalent in patients with generalized anxiety disorder, but was not associated with panic disorder, agoraphobia, or social phobia.
(42) In another study, patients with panic disorder were 
more likely to report sexual problems, particularly sexual aversion, than social phobics; PE was the most common sexual problem in men with social phobias.
(43)
Non-clinical, community-based studies have also demonstrated 
a relationship between mood and sexuality. In the Massachusetts Male Aging Study, an association was reported between ED and depressive symptoms, after controlling for other potential con-founding variables such as age and physical health.
(44) Angst(42)

found a relationship between depression and loss of sexual interest, particularly marked in women. In a US survey of heterosexual women, scores on a brief measure of mental health were strongly predictive of women’s distress about their sexual relationship and their own sexuality.
(26)
Although most studies have focused on negative effects of mood 
disorders on sexual interest and response, there is evidence that a minority of individuals experience increased sexual interest during negative mood states. Angst
(42) reported that among depressed

(42) reported that among depressed 
men, 25.7 per cent reported decreased, and 23.3 per cent increased, sexual interest, compared with 11.1 per cent and 6.9 per cent, respectively, of their non-depressed group. In contrast, among depressed women, 35.3 per cent reported decreased sexual interest and only 8.8 per cent reported increased interest (compared with 31.6 per cent and 1.7 per cent, respectively, of their non-depressed group). This paradoxical pattern of increased sexual interest dur-ing negative mood states has also been reported in non-clinical samples of men
(45) and women.(46) Although the origins of this 
pattern are not yet understood, it may well be problematic in various ways; for example, associated with sexual risk-taking or leading to sex being used as a mood regulator.

The impact of schizophrenia on sexuality is complex. Given the 
importance of dopaminergic neurotransmission to various aspects of sexuality, and the fact that most anti-psychotics are dopamine antagonists, one might expect ampliﬁ  cation of sexual interest or 
response in some form, at least during the more ﬂ  orid type one 
stage of the illness. Sexual thoughts and behaviours are common in 4.11.2 the sexual dysfunctions

SECTION 4  clinical syndromes of adult psychiatry 826
schizophrenia and there may be a relative increase in sexual activity. 
However, this is typically autoerotic or ‘compulsive’ without any real ‘object-relational’ quality.
(47) In view of the effects of this 
illness on interpersonal functioning, this is not surprising. Early studies suggested that loss of sexual interest was less likely in schizo-phrenia than in other types of psychiatric illness, although female schizophrenics were more likely to report a reduction in sexual interest than males.
(47) ‘Pre-schizophrenic personality’ , evident in 
the history of many cases, may also be associated with an interfer-ence with normal sexual development.
(b) Physical health and sexuality
The impact of poor physical health on sexuality may be relatively non-speciﬁ  c. For example, loss of well-being and energy associated

The impact of poor physical health on sexuality may be relatively non-speciﬁ  c. For example, loss of well-being and energy associated 
with chronic illness is likely to cause reduced sexual interest and arousability. Psychological reactions to the illness or condition (e.g. the effects of breast cancer on a woman’s body image and hence her sexual enjoyment) may also be important. In addition there are a variety of ways in which the health problem can directly affect sexual interest and/or response. In most cases we ﬁ  nd the evidence 
much clearer in men than in women.
(i) Damage to the neural control of genital response

This can involve peripheral mechanisms (e.g. autonomic neuropa-thy and peripheral neuropathy) or disease in the spinal cord (e.g. multiple sclerosis). Injury or surgery causing nerve damage may be involved (e.g. spinal cord injury, prostatectomy, or hysterectomy). The most likely consequences are ED in men and impaired vaginal response in women. There is no clear relationship between neural damage and PE but interference with normal seminal emission can occur, with resulting loss of ejaculation or retrograde ejaculation when, due to nerve damage to the pelvic muscles, the seminal ﬂ  uid

passes backwards into the bladder during ejaculation. Brain abnor-malities, such as epilepsy or cerebral tumour, can affect central control of sexual response, the precise effect depending on the site of the abnormality or tumour. In some cases the result is loss of sexual interest and arousability; rarely there is disinhibition of 
sexual behaviour.
(ii) Impairment of vascular supply of the genitalia
Genital response is dependent on increased arterial inﬂ  ow as well 
as alteration in venous outﬂ  ow. Vascular impairment can result 
from peripheral vascular disease, affecting the small vessels, or obstruction in a main artery. ED is also common in men who have ischaemic heart disease.
(iii)  Alteration of endocrine mechanisms affecting sexual interest, 
arousal and response
In males any cause of lowered testosterone (T) levels is likely to

In males any cause of lowered testosterone (T) levels is likely to 
produce loss of sexual interest and, to a varying extent, impairment of erectile response. Hypogonadism, if severe enough, will also be associated with loss of seminal emission (and usually orgasm).
In women, lack of oestrogen is associated with impaired vaginal 
lubrication. The effects of sex steroids, either oestrogens or andro-
gens, on sexual interest and arousability, are much less predictable. 
The evidence is consistent with there being a proportion of
women who depend on T for their normal level of sexual interest, 
but there are many women who can experience substantialreduction in T without obvious adverse sexual effects. The role of oestrogen in the more central aspects of women’s sexuality also remains unclear.
(48)Hyperprolactinaemia, usually resulting from pituitary adenomas

(48)Hyperprolactinaemia, usually resulting from pituitary adenomas 
and hypersecretion of prolactin, may be associated with loss of sexual interest, and in men, with ED. However, this is not always the case. The precise role of prolactin in human sexuality is not understood. Its central control by dopamine and serotonin con-tributes to the complexity. Adverse effects of hyperprolactinaemia on sexuality are probably more likely in men than women.
(iv) Metabolic disorders
Various forms of metabolic disturbance, such as that associated with hepatic or renal disease, may be associated with adverse effects on sexual interest and response, though the mediating mechanisms are not understood.
Some diseases affect sexuality through more than one of the

Some diseases affect sexuality through more than one of the 
above mechanisms. Diabetes mellitus is a good example. ED has long been recognized as a complication of diabetes and is more common in Type 1 than Type 2 diabetes. In diabetic men, ED can result from small vessel vascular disease and also autonomic and peripheral neuropathology. Diabetes is associated with hypogo-nadism in men. Lowered sexual interest and impairment of genital response have also been reported in diabetic women.
(c) Side effects of medication

In considering the complexities of pharmacological effects on sex-ual function, it is helpful to distinguish between excitatory and inhibitory mechanisms. In the brain, sexual excitation depends to a considerable extent on dopamine (DA) and noradrenaline (NA). DA is involved in the ‘incentive motivation system’ and is hence relevant to sexual interest. It is the D2 receptor that is most relevant to these sexual effects. It is also involved in the hypothalamic con-trol of genital response. NA, when acting centrally, is involved in central arousal, a key component of sexual arousal though not speciﬁ  c to it. In the periphery, depending on the receptor involved, 
NA can have inhibitory or enhancing effects on smooth muscle relaxation, a critical aspect of genital response. There are three principal NA receptors of relevance: (i) alpha-1, which is post-synaptic and mediates smooth muscle contractions, inhibiting

genital response, (ii) alpha-2 which is principally pre-synaptic, 
where it increases re-uptake of NA and hence reduces the amount of NA at the synapse, and (iii) beta-2, a peripheral receptor which mediates a relaxing effect of NA on smooth muscle in the urogeni-
tal system and elsewhere. Serotonin (5-HT) has a central role
in the inhibitory system. The two most relevant receptors are
the 5-HT2 receptor, which mediates the inhibitory effects and the 5-HT1A receptor, which is pre-synaptic and, comparable to the alpha-2 receptor, reduces 5-HT transmission. We can now consider the main adverse sexual effects resulting from medication; for a review, see.
(49)
(d) Anti-depressants

(49)
The clearest examples are the SSRIs which, by inhibiting the 5HT-1A receptor, increase serotonergic transmission. The most predict-able effect, in both women and men, is inhibition of orgasm and ejaculation. This effect is being exploited in the treatment of PE, with the development of short-acting SSRIs which can be used as needed prior to sexual activity. Other negative effects include reduced sexual interest and arousability, though they are less pre-dictable and not always easy to distinguish from the sexual effects of the affective disorder being treated. Tricylic anti-depressants also commonly produce sexual side effects. Two anti-depressants which

827
have less sexual side effects are bupropion, which is metabolized 
into a DA and NA re-uptake inhibitor, and nefadazone, which has a 5-HT2 antagonist effect.
(e) Anti-psychotic medication
These drugs, used for the treatment of schizophrenia and other psychotic disorders, involve a balance of DA antagonist and 5-HT agonist effects. Sexual side effects occur in around 60 per cent of men and 30–90 per cent of women using these drugs. The most common side effects are ED and ejaculatory difﬁ  culties in men and 
orgasmic dysfunction in women. It is not clear to what extent these effects are due to the DA antagonist or 5-HT agonist effects, or a balance of the two.
(f) Anti-hypertensive medication

Many drugs used to treat hypertension interfere with male sexual response. In the case of alpha-1 antagonists (e.g. prazosin), the peripheral effects would be expected to enhance erection, by reduc-ing adrenergic contraction of erectile smooth muscle and indeed priapism is an occasional problem. There is a low incidence of sex-ual side effects, mainly failure of ejaculation, and central alpha-1 blockade might reduce central arousal. Beta-blockers (e.g. propa-nalol), by blocking smooth muscle relaxation and leaving the alpha-1 induced contraction unopposed, commonly cause ED. Centrally acting anti-hypertensives (e.g. guanethidine) also inter-fere with sexual response, impairing erection, and blocking ejaculation. Clonidine, an alpha-2 agonist, causes erectile problems in about 25 per cent of cases. In this case the principal effect is likely to be reduced central arousal. For a review of the effects of

anti-hypertensive medication on male sexual response, see.
(50)
The effects of drugs on women’s sexuality have received far less 
attention. Research has mostly focused on difﬁ  culties in achieving 
orgasm. As orgasm only occurs after sufﬁ  cient sexual arousal, these 
effects may reﬂ  ect impairment of arousal but this has not been 
adequately assessed. Steroidal contraceptives, although associated with markedly reduced levels of free T, decrease sexual interest only in a minority of women.
(51) This, again, has been little studied and 
it remains possible that the adverse effects on sexual interest only occur in those women whose sexuality is ‘T dependent’ .
(51)
Management of sexual problems
In this section we will brieﬂ  y describe the principles of sex therapy

(51)
In this section we will brieﬂ  y describe the principles of sex therapy 
and the main forms of pharmacological treatment, followed by an outline of the process of assessment and selection of a suitable treatment plan. The growing awareness of the limitations of phar-macological treatments administered on an individual basis, dis-cussed earlier, has led to recognition that an integration of psycho-logical and pharmacological methods, with emphasis on the couple, may be the most appropriate treatment model in most cases.
Sex therapy
Although the approach ﬁ  rst introduced by Masters and Johnson(1)
has been adapted in various ways, the core treatment techniques 
remain. Originally developed for helping couples, the techniques can be modiﬁ  ed for use with individuals and with same-sex as well 
as heterosexual couples.
The key elements of the therapeutic process are:
(a)  clearly deﬁ  ned tasks are given and the couple asked to attempt

(a)  clearly deﬁ  ned tasks are given and the couple asked to attempt 
them before the next therapy session(b)  those attempts, and any difﬁ  culties encountered, are examined 
in detail
(c)  attitudes, feelings, and conﬂ  icts that make the tasks difﬁ  cult to 
carry out are identiﬁ  ed
(d)  these are modiﬁ  ed or resolved so that subsequent achievement 
of the tasks becomes possible
(e) the next tasks are set, and so on
The tasks are mostly behavioural in nature. They are chosen to 
facilitate the identiﬁ  cation of relevant issues but in some cases 
are sufﬁ  cient in themselves to produce change. The behavioural 
programme is in three parts. In the ﬁ  rst part the couple are asked to 
avoid any direct genital touching or stimulation and to focus on non-genital contact, alternating who initiates and who does the touching. These ﬁ  rst, non-genital steps are effective in identifying

important issues in the relationship, such as lack of trust or counter-productive stereotypical attitudes (e.g. once a man is aroused, he can’t be expected not to have intercourse). Once this stage can be carried out satisfactorily, and related problematic issues dealt with, the programme moves on to the second part, which allows genital touching to be combined with non-genital touching, with penile–vaginal intercourse still ‘out of bounds’ . In this second part more intra-personal problems, such as long-standing negative attitudes about sex, or the sequelae of earlier sexual trauma are likely to emerge. In the third part, a gradual approach to vaginal–penile contact and insertion is undertaken. Here the most relevant issues are ‘performance anxiety’ and fear of pain.
As the behavioural tasks reveal key issues that need to be resolved 
before moving on to the next stage, a variety of psychotherapeutic

before moving on to the next stage, a variety of psychotherapeutic 
approaches, including cognitive behavioural techniques, can be utilized. Although the stage at which particular issues emerge 
does vary from case to case, there is a tendency for problems identi-ﬁ ed through the ‘ﬁ  rst window’ , particularly those related to lack 
of trust and unresolved resentment, to appear during the ﬁ  rst stage 
of the programme. Intra-personal issues (e.g. as seen through the ‘second window’) are more likely to be recognized during the second stage.
The goals of therapy include helping the individual to accept and 
feel comfortable with his or her sexuality and helping the couple to establish trust and emotional security and to enhance the enjoy-ment and intimacy of their sexual interaction. An important point is that these goals do not include reversal of speciﬁ  c sexual dys-

functions. There are exceptions; for example, there are speciﬁ  c 
behavioural techniques to deal with PE and vaginismus (for details of these techniques, see Bancroft.
(52) However, the overriding prin-
ciple is that, assuming there is no abnormality of the basic physio-logical mechanisms involved in sexual response, normal sexual function (in terms of sexual desire, arousal, and genital response) will return once the above goals are achieved. In cases where impairment of physiological mechanisms does exist, the above goals of sex therapy are still helpful and integrate well with the use of pharmacological treatment.
Practical aspects
Although sex therapy varies in duration, 12 sessions over 4 to 5 months is typical. The therapist adjusts to the particular needs of the individual or couple. Treatment begins weekly with the interval between sessions extended once major issues like unexpressed 4.11.2 the sexual dysfunctions

SECTION 4  clinical syndromes of adult psychiatry 828
resentment or communication problems have been dealt with. The 
last two or three sessions are spaced out over a few months so that the couple have an opportunity to consolidate their progress and cope with any setbacks before termination. Open-ended arrangements about length of treatment are best avoided. A speci-ﬁ ed number of sessions are agreed on at the outset with the proviso 
that progress will be assessed and a decision made on that basis whether to continue for longer.
A more complete description of the sex therapy process is 
provided by Bancroft.
(52)
Pharmacological treatments for men
(a) Erectile dysfunction. Phosphodiesterase 5 inhibitors
The most important development in this ﬁ  eld was the serendipi-
tous discovery that sildenafil (Viagra ®), a PDE-5 inhibitor,

tous discovery that sildenafil (Viagra ®), a PDE-5 inhibitor, 
enhances erectile response. Dose titration is usually required, with available tablets containing 25, 50, or 100 mg. For more severe cases of ED, 100 mg taken about 1 hour before sexual activity is required. The maximal effects last for about 4 h. The most common side effects, that are dose-related, are headache, ﬂ  ushing, and 
dyspepsia.
Two further PDE-5 inhibitors have been developed and are 
now in use: tadalaﬁ  l (Cialis ®) and vardenaﬁ  l (Levitra ®). They are 
both comparable to sildenaﬁ  l in their efﬁ  cacy, the main differences 
being their speed and duration of action. Tadalaﬁ  l should be 
taken at least 30 min before sexual activity and has a half-life of 17.5 h; the treatment effect can persist for 24–36 h. Vardenaﬁ  l is

taken at least 30 min before sexual activity and has a half-life of 17.5 h; the treatment effect can persist for 24–36 h. Vardenaﬁ  l is 
pharmacokinetically similar to sildenaﬁ  l, but is more potent, with a 
dose range 5 mg to 20 mg. They are similar in their side effects, though the duration of these relate to the half-life of the drug. For all three drugs, the most important and dangerous drug interaction is with nitrates used for ischaemic heart disease; this is a strong contraindication for the use of PDE-5 inhibitors.
There is now an extensive literature demonstrating the efﬁ  cacy 
of sildenaﬁ  l in the treatment of ED, which has been well reviewed 
by Rosen and McKenna.
(53) Overall, treatment is effective in about 
75 per cent of cases. The effectiveness of tadalaﬁ  l and vardenaﬁ  l has 
also been demonstrated.
In spite of their efﬁ  cacy, the continuing use of PDE-5 inhibitors

In spite of their efﬁ  cacy, the continuing use of PDE-5 inhibitors 
appears to be limited. In a recent large study done in eight coun-tries, 2912 men identiﬁ  ed with ED were followed up; 58 per cent of 
them had sought medical help for the ED, but only 16 per cent of men maintained their use of PDE-5 inhibitors.
(7) Various reasons 
were given for discontinuation, including lack of appropriate infor-mation from the physicians, fear of side effects, partner concerns, and distrust of medications.
(b) Anti-adrenergic drugs

Alpha-2 antagonists may enhance sexual arousal by their central NA effects. One example is yohimbine, which has a modest thera-peutic benefit over placebo and is generally well tolerated. Phentolamine is an alpha-1 and alpha-2 antagonist used medically to treat hypertensive crises. It has been used, in combination with papaverine, to induce erection by intra-cavernosal injection, presumably mediated by its alpha-1 antagonist effect. Phentolamine administered systemically can also improve sexual arousal, presumably by blocking both the peripheral alpha-1 receptors and enhancing central arousal by blocking the alpha-2 receptors in the brain. Some evidence of beneﬁ  cial effects of phentolamine has been reported, although long-term follow-up revealed high 
attrition.
(c) Dopamine agonists

The main effects of dopamine agonists, such as apomorphine, are to induce genital response, probably via the hypothalamic oxytocinergic system. Early studies with apomorphine in men, while showing positive effects on erection, also demonstrated substantial side effects (mainly nausea and dizziness). Sublingual administration was developed to reduce such side effects and a number of placebo-controlled studies have shown this to improve erectile function
(54) but the occurrence of side effects remains a 
limiting factor.
(d) Melanocortin agonists
A recent development has been bremelanotide (PT-141), a metabolite of melanotan-II, and a melanocortin analogue, which probably works through the same oxytocinergic system as apomor-phine. Side effects similar to those with apomorphine occur, and further phase 3 research is required before the clinical value of this compound is established.
(i) Premature ejaculation

The orgasm inhibiting effect of SSRIs (see above) has been exploited in the treatment of PE. Paroxetine, sertraline, and ﬂ  uox-
etine, among others, have all been shown to be effective in this respect. However, continued use is required, and effects may not be apparent during the ﬁ  rst week. This raises the issue of side effects 
and the need to avoid sudden withdrawal.
More recently, PDE-5 inhibitors have been explored as a treat-
ment for PE. However, the beneﬁ  ts are not clear cut and may be 
restricted to cases of  ‘secondary’ PE. The most likely mechanism of action is reduction of the smooth muscle contraction involved in seminal emission.
(ii) Delayed or absent orgasm/ejaculation
At present there is no accepted pharmacological treatment for delayed or absent ejaculation or orgasm.
(iii) Low sexual desire
The most treatable but relatively infrequent cause of loss of sexual desire in men is hypogonadism. Where androgen deﬁ  ciency is evi-

dent, T replacement is indicated. Currently the most favoured route of administration is transdermal, either using cream or skin patch-es. One advantage of the transdermal route is that the hormone is absorbed into the skin and then released more gradually into the circulation, maintaining relatively physiological levels. In compari-son, intra-muscular injections of T (e.g. T enanthate) producesupraphysiological levels in the circulation, which then steadily decline. Oral routes are complicated by ﬁ  rst pass through the liver.
If loss of sexual desire is associated with hyperprolactinaemia, 
treatment with dopamine agonists, such as bromocriptine, is indicated.
Pharmacological treatments for women

At present pharmacological methods for treating sexual dysfunc-tion in women, although generating much interest and controversy, are very limited. Most attention is currently being paid to the use of T for treating low sexual desire. As considered earlier, the evidence of a role for T in women’s sexuality is inconsistent and the likeli-hood is that it is important for some women and not others.

829
The most convincing evidence of the beneﬁ  ts of T are in women 
who have been ovariectomized and have therefore experienced a substantial reduction in their androgen levels. Much of thisevidence, however, indicates that supraphysiological levels ofT result from treatment; thus, it remains uncertain whether the beneﬁ  ts result from correction of T deﬁ  ciency or pharmacological 
effects of high levels of T. For this reason, and because of uncer-tainty about possible long-term risks, there has been a reluctance to approve such treatments, particularly in women with intactovaries.
(48)
Attempts to treat sexual desire/arousal problems with PDE-5

(48)
Attempts to treat sexual desire/arousal problems with PDE-5 
inhibitors have so far proved unsuccessful, although there may be subgroups of women who benefit. Other pharmacological approaches which are being explored in women include the use of phentolamine, apomorphine, bupropion, and bremelanotide (PT-141). But further research is required before any of these can be recommended for clinical use. For more details of the above treatments, see Bancroft.
(52)
In a 1997 review, Heiman and Meston(55) concluded that there 
was evidence for empirically validated treatments for orgasm prob-lems in women and ED in men. There was inadequate support for effective treatments for low sexual desire, sexual aversions, dyspa-reunia in women and men, and delayed orgasm in men. What is striking is that of the 90 studies involving psychological treatments cited in this review, only two were published since 1990, and 60 of them before 1980.

In the decade since this review, there have been a few controlled 
trials involving cognitive behaviour therapy (CBT) for womenwith vaginismus,
(56) vulvar vestibulitus,(57) and couples presenting 
with problems of low sexual desire,(58) all suggesting positive 
effects. Further outcome studies of psychological therapies that identify predictors of successful outcomes are badly needed.
Combined psychological and medical treatment
There have now been a number of studies in men that have compared combined psychological and pharmacological treat-ments, with either used separately. These have been reviewed by Althof
(6) and include studies combining psychotherapy with 
sildenaﬁ  l, and counselling with intra-cavernosal injections or with 
vacuum devices. In each case, the combination produced signiﬁ  -
cantly better results than the medical treatment alone.
Planning a treatment programme
When couples present with sexual difﬁ  culties, one of them is usu-

ally regarded as having the problem. However, both partners should be carefully assessed whenever possible. There are three stages to assessment; ﬁ  rst, to facilitate the decision about whether sex therapy 
is appropriate; second, to identify issues relevant to the sexual 
problem that need to be resolved, and third, to determine whether 
medication or other treatments are required.
Keeping in mind the distinction between a sexual problem that is 
adaptive or appropriate given an individual’s current circumstances and one that is maladaptive (and can perhaps be considered a

adaptive or appropriate given an individual’s current circumstances and one that is maladaptive (and can perhaps be considered a 
‘dysfunction’), we can assess each individual’s case through the three conceptual ‘windows’ described earlier. Are there problems in the couple’s current relationship or situation, which would make inhibition of sexual responsiveness in either partner understand-able or adaptive? Does either individual give a history that suggests vulnerability to sexual problems? Are there are any mental or phys-ical health issues or medication use in either partner that could be having a negative effect on sexual interest or response?
(a) The initial interview

Although not all of the details can be obtained during the initial interview, assessment of the following topics should be carried out: the nature of the problem, including an assessment of level of sexual interest and response in each partner; identiﬁ  cation of other 
assessments that may be needed (e.g. physical examination, blood tests); commitment and motivation of each partner to improving the relationship; and, assessment of the mental state of each partner. If both partners are present, each should be interviewed separately following a conjoint interview. As far as possible, questions should be asked about each individual’s sexual history, the nature of the current relationship, contraceptive use and reproductive history, and alcohol or recreational drug use.
At the end of the initial interview, the clinician should provide a

At the end of the initial interview, the clinician should provide a 
preliminary formulation of the nature of the problem and the types of intervention that may be helpful. Whatever treatment methods 
are used, it is important to continue to see the couple together to 
monitor progress and provide counselling as needed.
If there is no evidence of causal factors of the kind viewed 
through the ‘ﬁ  rst’ or ‘second’ windows (see above), then a trial of 
pharmacological treatment may be appropriate. In such cases a physical examination and, where relevant, laboratory investigations would normally be arranged before starting treatment. It is impor-
tant to have a good ‘clinical baseline’ before embarking on pharma-
cological interventions.
If there are any indications of problems or issues, particularly of

If there are any indications of problems or issues, particularly of 
the kind that invoke inhibition of sexual response, which need to be resolved, then pharmacological interventions should not be considered as a ﬁ  rst step. In many cases, more assessment is required 
before such factors can be adequately assessed. There are then two options: (i) further interview(s) to explore such issues or (ii) starting on a programme of sex therapy. The rationale for the second option is as follows. The initial two stages of sex therapy (i.e. involving non-genital and then genital touching with no 
attempts at vaginal intercourse) are particularly effective at identi-fying relevant issues underlying the problem. Furthermore, the 
process involved in those early stages is likely to beneﬁ  t any sexual 
relationship, even those without obvious problems. After three or

relationship, even those without obvious problems. After three or 
four sex therapy sessions, a re-appraisal would be made and a 
decision taken whether to continue with sex therapy alone, or to combine it with an appropriate pharmacological method. For 
example, with a couple where the man has erectile problems, it is 
easier to assess the indications for the use of a PDE-5 inhibitor after the couple have gone through the ﬁ  rst two stages of the programme 
where there is no ‘performance pressure’ and no need for an erec-
tion to occur. Similarly, it is often informative to see what impact 
this behavioural programme has on the individual who has com-plained of reduced sexual desire, before attempting to deal with the problem pharmacologically or hormonally.4.11.2 the sexual dysfunctions

SECTION 4  clinical syndromes of adult psychiatry 830
Ideally, the use of the pharmacological method should then 
proceed in combination with the continuation of the sex therapy programme. In that way a gradual transition to a satisfying sexual relationship can be achieved without renewed ‘performance pres-sures’ . If, however, progress continues to be made with sex therapy, then the addition of pharmacological interventions may not be 
necessary. It should be explained to the couple that, whereas phar-macological treatments often have beneﬁ  cial effects on sexual 
response, they do not ‘cure’ the problem, which is likely to recur once the medication is stopped. Furthermore, there are often side effects that have to be dealt with. There is, however, some evidence that when medication is combined with sex therapy, the pharma-cological component can be gradually withdrawn, or only used intermittently.
Ethical aspects of clinical management

In assessing individuals or couples with sexual problems it is clearly important to assure them that the information they provide will be treated as highly conﬁ  dential. It is appropriate to have separate 
case ﬁ  les for sexual problem clinics, rather than ﬁ  les used in other 
clinics. In this way the ﬁ  les can be kept secure. Some overview of 
the information presented to the clinic by the referring clinician should be provided at the start of the assessment. Information to be passed back to the referring clinician by letter or word of mouth should be agreed with the client(s) in advance, particularly if any highly sensitive issue emerged during the assessment. When assess-ing a couple, and seeing each partner separately, it is important to establish whether each individual agrees to any information not known by the other being shared during the joint sessions (e.g. 
details of previous sexual relationships). When offering a course

details of previous sexual relationships). When offering a course 
of treatment or further assessment, the individual or couple should be fully informed about what is involved before being asked to make their decision.
A more challenging ethical issue relates to cultural values. Much 
of the process of sex therapy involves the therapist encouraging and ‘giving permission’ for speciﬁ  c forms of sexual interaction, as 
well as more general patterns of interaction within the relationship (e.g. ‘self asserting’ and ‘self protecting’). It is important for the therapist to keep in mind that many of these principles are based on western middle class values. When working with a couple from a different culture, or even a different social class to the therapist, there should be awareness, openness, and discussion about con-trasting values of cultural or religious origin. In this way differences can be negotiated, rather than have therapist values imposed.
When to seek specialist help

The treatment programme described above can be applied by psychiatrists in practice providing that they (i) are comfortable asking detailed questions about sexual behaviour and response, (ii) have experience working psychotherapeutically with couples, and (iii) are familiar with cognitive behavioural methods of treat-ment. They have the advantage over many non-medically qualiﬁ  ed 
sex therapists of being able to prescribe medications in combina-tion with a behavioural approach to sex therapy.
Specialist help should be obtained if there is evidence of a physi-
cal condition which requires detailed assessment and treatment, or if, after a reasonable trial of integrated psychological andpharmacological treatment, the sexual problem remains unre-

solved. In some such cases, the specialist help should be fromsomeone with expertise in sexual medicine (e.g. urologist, gynae-cologist). In other cases, where the psychological aspects remain unclear or difﬁ  cult to resolve, referral to  an experienced sex therapist 
is appropriate.
American Association of Sex Counselors, Educators, and Therapists 
(AASECT). http://www.aasect.org/.
British Association of Sexual and Relationship Therapists (BASRT) 
[http://www.basrt.org.uk].
Bancroft, J. Human sexuality and its problems  (3rd edn). Elsevier, Oxford, 
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Kingsberg, S., Althof, S.E., and Leiblum, S. (2002). Books helpful to patients 
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28, 219–28.

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SECTION 4  clinical syndromes of adult psychiatry 832
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4.11.3 The paraphilias
Deﬁ nition of the condition
The characteristic essential to all paraphilias is the presence of a 
persistent and/or recurrent, sexually motivated interest that causes harm. This deﬁ  nition has several implications.
Interest versus act
Paraphilias can exist even if they have never been acted upon. By 
deﬁ nition, all paraphilias begin with a sexual thought and, like

deﬁ nition, all paraphilias begin with a sexual thought and, like 
non-paraphilic interests, the majority of sexual fantasies are never fulfilled in reality. Sexual acts are only paraphilic if they are motivated by harmful sexual interests. For example, an individual with paedophilia (sexual interest in children) may act on this interest by masturbating while viewing non-pornographic children’s television shows. However, an individual who uninten-
tionally downloads pictures of children from the Internet while meaning to download adult pornography should not be considered 
paedophilic (even though he or she may still be criminally liable).
Persistent versus opportunistic

Paraphilias are characterized by their persistence. Therefore a single paraphilic thought or activity, especially if it occurs during unusual circumstances, is unlikely to be indicative of a true paraphilia. For example, a woman who while on a vacation and under the inﬂ  u-
ence of alcohol exposes herself once to group of strangers in a bar, would not normally be considered to have exhibitionism (sexual arousal from exposure to strangers). Opportunistic activity that is not sexually motivated, even if it is ongoing, is also exclusionary. A pimp who coerces women to exchange sexual activities for drugs or money, would not meet criteria for sexual sadism even though he repeatedly engages in opportunistic sexual activity with other-wise unwilling participants because, for the pimp, the motivation is ﬁ nancial rather that sexual.
Harm versus happenstance

Many sex acts are intimate. Therefore it should come as no surprise 
that participants can be harmed. Unfortunately whenever sexual activities are considered, ‘harm’ tends to be deﬁ  ned somewhat 
solipsistically. Paraphilias are characterized by sexual interests or behaviours in which harm is more or less inevitable rather than accidental or random. For example, although sexual intercourse may expose the participants to a number of dangers including sexually transmitted diseases, possibly unintended degrees of intimacy, or subsequent events (e.g. pregnancy), by and large, con-
sensual sexual activity between adults does not inevitably lead to disaster.
In contrast, true paraphilic interests are by deﬁ  nition, harmful. 
For example, a woman who can only become sexually aroused if she is choked to unconsciousness (asphyxophilia), exposes herself

For example, a woman who can only become sexually aroused if she is choked to unconsciousness (asphyxophilia), exposes herself 
to unintended harm including cerebral anoxia and possible death. The paraphilias associated with crime (e.g. voyeurism, exhibition-
ism, frotteurism, criminal sadism, and paedophilia) involve non-consensual imposition of sexual activity onto others. Other non-criminal paraphilias (e.g. transvestic fetishism) become prob-lematic when they interfere with the ability to maintain a recipro-cal emotional relationship. Most men with transvestic fetishism do not seek therapy and there is no indication they should, unless the interest begins to cause harm. Paraphilic transvestites are sufﬁ ciently dependent on cross-dressing that it causes distress.

Transvestic fetishism is a good example of a paraphilic condition in which the individual symptoms (wearing women’s clothing while masturbating or engaging in sexual relations) are not problematic. However, when the sexual interest becomes so pervasive that it interferes with consensual sexual relations, a diagnosis is permissible. Transvestic fetishism is very responsive to treatment with selective serotonergic re-uptake inhibitors prescribed at doses low enough to avoid inhibited orgasm.
Pathologic versus unconventional
While paraphilias are characterized by deviant sexual interests, unconventional interests alone are not sufﬁ  cient to meet criteria 
for a true paraphilic condition. This is a persistent source of confu-sion in two speciﬁ  c situations.
(a) Homosexuality
A primary sexual interest in the same sex (homosexuality) is statis-

tically rare. However, there is nothing about a primary same-sex interest that necessarily leads to harm to anyone. Sexual interest in a woman is no more harmful for a heterosexual man than it is for a lesbian woman. Although homosexuality is statistically and socially unconventional, the absence of inevitable or likely harm excludes same-sexed sexual interest from being paraphilic.
(b) Sadomasochism
Sexual arousal from control (sadism) or from being controlled (masochism) illustrates a second way in which unconventional sexual interests may fail to meet criteria for designation as a para-philia. While harm is a necessary criterion for paraphilias, it is not sufﬁ cient. For example, while many conventional sports involve

competition and attempted domination of an opponent, theactivity is not primarily sexually motivated. Therefore, although boxing involves the intentional attempt to render an opponent unconscious via inﬂ  iction of a cerebral concussion (knockout), 
pugilism is not a paraphilia because it is not primarily sexually motivated.
The converse is also true. Many men and women engage in inter-
actions that are sexually motivated and which involve negotiations about power and control, domination and submission. These 
themes have become highly organized and regulated within social 
groups under the general category of ‘BDSM’ (bondage, domina-tion, submission, sadism, masochism). Publications describing the BDSM ‘lifestyle’ universally champion the credo: ‘safe, sane, and

833
consensual’ . Therefore, men and women who engage in ‘BDSM’ 
sexual activities, although they may involve statistically and/or socially unconventional activities, do not meet criteria for any paraphilia disorder. In fact, it is arguable that anyone who issexually aroused by the idea of engaging in ‘safe, sane, and con-sensual’ activities is less paraphilic than those with conventional 
sexual interests who are willing to compromise some of these meritorious criteria in pursuit of conventional sexual interac-
tions. For a more complete discussion of sexual violence andsexual sadism.
(1)Classiﬁ  cation
Table 4.11.3.1 consists of a partial list of the over 100 paraphilic 
disorders described in the literature. Classiﬁ  cation of the paraphil-
ias remains controversial. This is due to two issues. The ﬁ  rst is that 
many paraphilias have been assigned names based on Latin or 
Greek etymology. For example, retifism refers to a paraphilic

interest in shoes more commonly known as a ‘shoe fetish’ while ‘reniﬂ  eurs’ are individuals with sexual arousal from the smell of 
urine. More complete listings of paraphilic disorders has been
Table 4.11.3 .1 Paraphilic sexual disorders
Paraphilia DSM- IV TR ICD-10 Essential feature: persistent sexual 
arousal towardsComments
Acrotomophilia 302.9 F65.9 Amputees

Apotemnophilia 302.9 F65.9 Being an amputeeAsphyxiophilia 302.9 F65.9 Being asphyxiated Also known as ‘autoerotic asphyxia’Biastophilia 302.9 F65.9 Non-consensual adult intercourse Also known as paraphilic rapism or raptophiliaExhibitionism 302.4 F65.2 Exposure to strangersFetishism 302.81 F65.0 Inanimate objects Not vibratorsFrotteurism 302.89 F65.8 Rubbing groin without consent ICD has no speciﬁ  c listingMysophilia 302.9 F65.9 ‘Filth’ Typically involving ‘soiled’ (worn) pantiesNecrophilia 302.9 F65.9 CorpsesPaedophilia 302.2 F65.4 Children ICD does not differentiateAttractionMalesFemalesBothExclusivityIncest onlyExclusiveNon-exclusivePolyembolokoilamania 302.9 F65.9 Insertion of objects Associated with Smith McGinnis syndrome. (Not clearly paraphilic)

Scoptic syndrome 302.9 F65.9 Being castratedScoptophilia 302.9 F65.9 Consensual viewing Paraphilic only if problematicSexual masochism 302.83 F65.5 Loss of control ICD combines into SadomasochismSexual sadism 302.84 F65.5 Non-consensual control ICD combines into sadomasochismSomnophilia 302.9 F65.9 sleeping sexual partnerTelephone scatalogia 302.9 F65.9 Obscene phone callsTransvestic fetishism 
with gender dysphoria302.3 F65.1 Wearing clothes of the opposite sex ICD does not subclassify
Urophilia 302.9 F65.9 Urine
Voyeurism 302.82 F65.3 SpyingParaphilia NOS 302.9 F65.9 Paraphilias not otherwise speciﬁ  ed ICD: Disorder of sexual preference unspeciﬁ  edOther disorders of 
sexual preferenceF65.8 Other paraphilic disorders4.11.3 the paraphilias

SECTION 4  clinical syndromes of adult psychiatry 834
published (c.f. Love, 1999). In addition, many of the paraphilias 
involve sexual interest in the characteristics of the sexual partner(s). Often some interest in assuming the same characteristics is evident and receives a unique name. The most obvious example is sado-masochism which the DSM classiﬁ  cation divides into sadism and 
masochism while in the ICD classiﬁ  cation the two complimentary 
conditions are combined.
The second problematic diagnostic issue in the classiﬁ  cation of

The second problematic diagnostic issue in the classiﬁ  cation of 
the paraphilias concerns the need to describe both unconventional sexual behaviours and problematic sexual behaviours. For example, while sexual arousal from cross-dressing is unconventional, it  tech-nically does not meet criteria for transvestic fetishism unless it causes distress. In the case of paraphilias involving criminal interests (e.g. paedophilia) issues arise if a person reports persistent sexual interest in children but no distress or wish to act on the paedophilic interest. Newer diagnostic criteria likely will address this issue.

Similar to most psychiatric conditions, paraphilic disorders are diagnosed primarily on the basis of self-reported symptoms. Paraphilias differ from most other psychiatric disorders in two ways: (i) many paraphilias involve illegal interests and (ii) objective measures of the primary criteria (in this case sexual interest) are available.
Illegal sexual interests
Paraphilic interests do not necessarily lead to illegal activities, and vice versa. Therefore, ‘Not all paedophiles are child molesters and not all child molesters are paedophiles’ .
With few exceptions, individuals with paraphilic interests not

With few exceptions, individuals with paraphilic interests not 
only know they have abnormal sexual interests but also wish they could replace them with ‘normal’ ones. Many confuse fantasy with reality, thinking that illegal sexual interests are equivalent to having committed a sex crime. A major issue in the diagnosis of paraphilic disorders is distinguishing between legal and psychiatric concerns (see Management section below for further details).
In addition to legal issues, clinicians should also consider several 
other diagnostic issues:
(a) False accusations

At one time accusations by children of sexual assault by adults were considered to be almost certainly true since it was assumed that children could not know about sex. A typical assertion would be that a child could not possibly describe acts such as sexual inter-course or ejaculation unless they had been sexually assaulted. Clearly this was before the widespread availability of pornographic videos, DVD’s, cable TV networks, and the Internet.
Beginning in the 1990s, adults began to report they had been

Beginning in the 1990s, adults began to report they had been 
sexually abused as children but had only recently recovered their memories of the assault. In part this trend seems to have been due to two factors: the decision in the United States to reset the time at which the statute of limitations required a sexual offence to be reported to the time at which the offence was recalled; and the believe that failure to recall sexual abuse was a sign that it had occurred.
(b) False confessions
While less frequent, false reports of paraphilic interests have also been described.
(2) The most frequent presentation of false para-philic symptoms takes the form of a man or woman with depres-

sion who reports obsessions involving often exceptionally troubling sex crimes. While a detailed phenomenologic examination of this phenomenon has not been published, several characteristics are typical. The individual often has a history of a mood disorder or is in circumstances in which affective disorders are more likely (e.g. post-partum). The sexual obsession typically involves children to whom the patient has access (it is rare for the patient to report spontaneous fantasies of sexual interactions with unknown children). Most importantly, the fantasies are extremely ego-dystonic. Asked 
if they ever masturbate to their paraphilic fantasies, they typically

if they ever masturbate to their paraphilic fantasies, they typically 
respond with horror and, unlike those with true paraphilias, often describe self-loathing indicative of a change in self-esteem due to depression. A danger of false confessions or admission of false paraphilic interests has also been noted in men and women with intellectual disability.
(c) Co-morbid conditions
People rarely seek treatment on their own speciﬁ  cally for paraphilic 
disorders. This is due to unfortunately widespread false beliefs that (i) there are no effective treatments for paraphilias, (ii) embarrass-ment about discussing paraphilic symptoms, and (iii) in the case of paedophilia, the mistaken belief that reporting a sexual interest in children necessarily requires that the patient be reported to the police (please see Management below for more comments on this 
problem). Since paraphilias themselves rarely motivate helpseek-ing, clinicians should include other conditions in the differential

problem). Since paraphilias themselves rarely motivate helpseek-ing, clinicians should include other conditions in the differential 
diagnoses both as alternative explanations for the problem and as co-morbid conditions that may be present in addition to the paraphilia. The most frequent of these are mood disorders, sub-stance abuse problems including alcohol, marital disorder, and legal problems.
Less common are organic disorders including brain injuries.
(3)
Surprisingly, given the importance of sex hormones in the develop-ment and expression of sexual characteristics, endocrine disorders affecting the sex hormones are rarely implicated. This may be because testosterone in men with normal or elevated hormone levels are more closely associated with violence and aggression than with alterations in the direction of sexual interest.
(1) One exception

(1) One exception 
is hypogonadism associated with Klinefelter’s syndrome. In some men with Klinefelter’s syndrome, paraphilic problems become apparent when testosterone is prescribed to correct hypogonadism. In those men with Klinefelter’s syndrome and paraphilic interests, addition of testosterone appears to unmask rather than cause 
previously unexpressed paraphilic conditions.
A more controversial question involves a possible association 
between paraphilias and intellectual disability. Some research has supported the hypothesis that, as a group, men with paedophilia 
have below average intelligence. However, alternative explanations 
are possible. For example, most men with paedophilia come to attention when they are arrested. The fact that men with intellec-
tual disability are more likely to be arrested and are over-represented 
in the criminal justice system may skew the data. Those who live in supervised housing are also more likely to have private activities

in the criminal justice system may skew the data. Those who live in supervised housing are also more likely to have private activities 
not only discovered by staff but also labelled by staff as deviant. 
In addition, men with intellectual disability frequently have
impairments in social skills that can certainly contribute toproblematic sexual behaviours independent of paraphilic interests. This phenomenon has been described as ‘counterfeit deviance’ .
(4)

835
One meta-analytic study supporting an association between paedo-
philia and intellectual disability found the mean I.Q. of sex offend-ers to be only ﬁ  ve I.Q. points below the mean I.Q. of non-sexual 
offenders.
(5) While cognitive ability is important in determining 
level of risk and in planning treatment (see below) it would be a diagnostic mistake to conﬁ  rm or refute a diagnosis of paedophilia 
on the basis of intelligence.
A further area of controversy involves the question of whether

A further area of controversy involves the question of whether 
having one paraphilia predisposes to having other paraphilias? The answer depends on whether the assessor is a ‘lumper’ or a ‘splitter’ . John Money viewed paraphilias as ‘vandalized lovemaps’ that were unique. He argued that a paedophile might begin by spying on children, then surreptitiously touching them, then engaging in sexual relations. It was his view that it was more accurate to label the disorder as paedophilia (since this explains the motivation behind the varied behaviours) as opposed to making a diagnosis of voyeurism, frotteurism, and paedophilia. Clearly both approaches have strengths and weaknesses. Most important is to be aware of both diagnostic methods when evaluating incidence or prevalence reports.
Prevalence of paraphilic disorders

Any discussion of the number of people with paraphilic disorders in the population must begin with a series of caveats. The most important is the fact that the majority of the information available is derived from studies of men convicted of sex crimes. This is a signiﬁ  cant problem since not all paraphilias are associated with sex 
crimes. The problem is compounded by the fact that many para-philic disorders remain undiagnosed either because assessment was never requested, clinicians did not gather sufﬁ  cient information, or 
because the person with the paraphilic disorder was unwilling or unable to disclose the symptoms. Further degrees of confusion and subsequent dispute are added by inconsistent application of exist-ing diagnostic criteria (for example confusing child molesters with paedophiles) or by differing opinions about whether or not to subdivide paraphilic disorders (e.g. diagnosing a person who lures

children into sexual activity by exposing to them as a paedophileor as both a paedophile and an exhibitionist). T o date, insufﬁ  cient 
attention has been paid to the importance of precise deﬁ  nitions
of what is being measured, the difference between point andperiod prevalence, and the potentially significant differencesattributable to independent characteristics of the populations being studied. For example, a report on the incidence of ‘sexual sadism’ based on a point prevalence study of sexual assault of womenand children in a country in which war is being waged, while important, has little to do with an analysis of the period prevalence of sexual sadism in, for example, North America. There is alsoan widespread but unwarranted assumption that studies basedon criminal populations can be easily generalized to otherpopulations.
Fortunately, with these above caveats in mind, a signiﬁ  cant

Fortunately, with these above caveats in mind, a signiﬁ  cant 
resource to answer epidemiologic questions is now available both in text form and, more importantly, in the form of a constantly updated Internet Web site: http://www.kinseyinstitute.org/ccies/. This Web site, currently under development and hosted on the Kinsey Institute web page, provides free access to reports by noted sexologists on sexual behaviours in 60 countries and six continents. Included in the chapters on most countries are sections dealing 
with both paraphilic disorders and ‘unconventional sexual behav-iours’ . This is important since different cultures may place different significance on sexual behaviours both in public and private. The fact that each chapter is multi-authored by sexologists who live in the country being described also likely adds to the cred-ibility of the information.
From perusal of the information available several statements

From perusal of the information available several statements 
about the epidemiology of paraphilic disorders can be made with reasonable conﬁ  dence.
(a)  Men are more likely than women to be arrested for 
sexually motivated crimes
Most (but not all) illegal activities are non-consensual. Those that 
are sexually motivated have a high likelihood of being associated with a paraphilia. Data to support this observation is derived primarily from review of the unequal ratio of men and women convicted of sex crimes. While there are increasing numbers of women (especially adolescent females) being convicted of child sexual abuse, men are still the vast majority. From a criminologic perspective men seem more willing to commit crimes of all types, especially those that involve confrontation (verbal, physical, and sexual). This is of signiﬁ  cance since two widely employed actuarial

risk assessment instruments, the Violence Risk Appraisal Guide (VRAG) and Sex Offender Risk Appraisal Guide (SORAG) rely heavily on the Hare Psychopathy Checklist (HPCL) which itself 
has been associated with criminal activity independent of sexual interest. This may explain why some researchers believe that a com-
bination of high scores on the HPCL combined with deviant scores on phallometric testing are associated with high risk of re-offence (either violent and sexual) (for more information please see the Hare Web site listed below).
(b)  With the exception of internet-related sex crimes, the 
frequency of sex crimes of all types are on the decline
This welcome ﬁ  nding has been reviewed extensively elsewhere.(6)
It is important to note that while this trend of decreasing fre-

quencies of sex crimes excludes countries in the midst of war or major political and social upheaval, the trend is occurringworldwide. Unfortunately the reason for this trend is unknown. One controversial explanation is a wider availability of porno-graphic materials, beginning with videotapes in the 1980s andnow exploding with the Internet. One study noted, during a time of increased availability of pornographic materials, an 85 per cent decrease in numbers of juvenile offenders in Japan from 1803 in 1972 to 264 in 1995.
(7) The increase in Internet-related crimes 
combined with an apparent decrease in other types of sex crimes invites the unproven speculation that one may be substituting for the other.
(c) Paraphilic disorders are not new
A ﬁ nal important point to be made about the epidemiology of

A ﬁ nal important point to be made about the epidemiology of 
paraphilic disorders is that they are not new. Historic texts on the topic clearly describe not only sex crimes but also the same phe-nomenologic characteristics seen by clinicians today. If there is a change, it is towards increasingly earlier detection of paraphilic behaviours, not only at a younger age,
(8) but also before criminal 
acts have been committed.
Table 4.11.3.2 summarizes generally accepted prevalence 
estimates for the DSM-IVTR paraphilias.4.11.3 the paraphilias

SECTION 4  clinical syndromes of adult psychiatry 836
Aetiology
Like most psychiatric disorders, the ultimate causes of paraphilic 
disorders are unknown. Like most groups of psychiatric disorders, they undoubtedly have multiple contributing factors.
Four major explanatory perspectives have been identified: 
‘disease’ , ‘behavioural’ , ‘dimensional’ , and ‘life story’ .
(9) Each per-
spective has had advocates that can be traced to the beginning of the twentieth century.
The disease perspective
The disease perspective is perhaps the most familiar to physicians since it is based upon an attempt to combine signs and symptoms into syndromes or disorders via pathophysiologic mechanisms.
In 1886 Krafft-Ebing published Psychopathia Sexualis: A Medico-
forensic Study  in which he described a large series of patients with a 
variety of sexual disorders, whom he had examined in his forensic psychiatry practice.
(10) Using a disease perspective he advanced the

(10) Using a disease perspective he advanced the 
hypothesis that masturbation caused a physiologic imbalance that was a major causal factor in development of sexual deviancy. Krafft-Ebing was widely criticized for his acceptance and perpetuation of the degeneration theory of masturbation (the now discarded theory that masturbation itself could cause progressive degrees of physiologic harm leading to increasingly severe psychopathology), and for his failure to clearly differentiate between extreme and mild forms of sexual deviancy.
While Psychopathia Sexualis  is now considered a landmark text 
in human sexuality, its acceptance was limited because it was published at a time when other etiologic explanations for the para-
philias were becoming important. One criticism of Krafft-Ebing’s 
disease perspective was his tendency to focus on illness rather than

disease perspective was his tendency to focus on illness rather than 
wellness or normality. In this context, Brautigam’s criticism of Krafft-Ebing’s Psychopathia Sexualis  foreshadows current criticisms 
of etiologic theories of the paraphilias that rely on the disease perspective:
This ﬁ  rst great and distinguished complete presentation and inventory 
of that ﬁ  eld has the character of a large catalogue of perversions. In a

of that ﬁ  eld has the character of a large catalogue of perversions. In a 
picture book-like series are offered the most monstrous cases of his time and history, particularly cases collected by Krafft-Ebing himself as a widely sought medico-legal consultant. The perversions are described in their most extreme forms. This collection of brutal necrophiliacs, anthropophages, sexual murderers,and sodomites, of cunning and cultured sadists, masochists, and transvestites has in its degree of deviation never been surpassed. By this extreme presen-tation Krafft-Ebing has moved sexual disorders away from general 
sexuality.
(11)
Magnus Hirschfield was a contemporary of Krafft-Ebing 
who also employed a disease perspective in an attempt to identify abnormal pathophysiology in individuals with identiﬁ  ed sexual

(11)
who also employed a disease perspective in an attempt to identify abnormal pathophysiology in individuals with identiﬁ  ed sexual 
problems. Although he is best known for his studies of castrated males and for his emphasis on the importance of hormones on sexual behaviour, Hirschﬁ  eld also drew an important distinction 
between the simple description of observed behaviours and proof of their aetiology. His argument that describing a behaviour was not sufﬁ  cient to explain its cause led him to distinguish between 
homosexuality, transsexualism, and fetishistic transvestism, in which the same behaviour (cross-dressing) could be shown to have different motivations and therefore presumably different causes.
(12)

(12)
His observation that sexual orientation and behaviour may have variable determinants was important since it emphasized the need to look for underlying causes of behaviour from a disease perspec-tive while at the same time opening the door for collaboration with behavioural researchers.
Behavioural perspective
Although Albert Moll felt that sexual disorders could be treated with ‘association therapy’ (a precursor to modern behaviour modi-ﬁ cation therapy), he felt learning alone could not account for all 
sexual deviations:
Were a single sexual experience, and, indeed, the first sexual experience to induce a lasting association between sex drive and the object of the ﬁ  rst sexual experience, then we would have to ﬁ  nd sexual

perversion everywhere. Where are there to be found people who initially satisﬁ  ed their sexual impulse in a normal manner?
(13)
By extending consideration of sexual development from child-
hood to adulthood, Moll was able to answer Brautigam’s criticism of Krafft-Ebing’s research by studying normal as well as abnormal sexuality.
Albert Moll and Alfred Binet, used behavioural perspectives to 
study sexuality by directing attention to the associations between behaviours and their reinforcers. Binet re-examined the case histo-ries of Krafft-Ebing’s patients and argued that sexual deviations which had been presumed to be caused by disease or degeneration could have been caused by learned associations. He noted that many of the reported cases he studied also had ‘chance associations’ 
that could explain the development of the sexual deviation. These 
observations implied that, given a specific set of reinforcedTable 4.11.3 .2 Frequency/prevalance of paraphilias

Paraphilia Prevalence/frequency Comments
Exhibitionism No reliable data 40–60% of females report 
having been exposed to 
Evidence suggests a decrease 
in frequency of exhibitionism after age 40
Fetishism No reliable data Depending on population 
studied, rates range from 0.8% 
to 18% of men
Frotteurism No reliable general 
population dataOnly paraphilia claimed to 
decrease in frequency after age 
25 (DSM-IV-TR p. 570)
Paedophilia Frequency: 300 000 abused 
children per year in the USA1988 data; does not account 
for repeat offences
Sexual sadism 3% to 20% of general 
populationData do not distinguish 
between criminal and 
non-criminal sexual interests
Sexual 
masochism5% to 10% of general 
populationData does not distinguish 
Transvestic

Sexual 
Transvestic 
fetishism1% of men True prevalence unknown 
in part due to idiosyncratic diagnostic criteria
Voyeurism No reliable data Most studies of voyeurism 
involve offenders with 
co-morbid paraphilic interests

837
experiences, any individual could become paraphilic. The proposi-
tion that all people could potentially acquire paraphilias if they were unfortunate enough to have been exposed to the necessary abnormal formative experiences was more fully developed by investigators using a dimensional perspective.
Dimensional perspective
The dimensional perspective is characterized by an avoidance of rigid categorical classiﬁ  cations in favour of continuous descriptors. 
Variations in sexual interests, including paraphilic interests, are explained as statistical extremes of normal behaviour without necessarily implying that a disease process is present. From a dimensional perspective, paedophilia would be understood as an extreme variation of the widespread tendency to equate youth with sexual attractiveness. The work of Haveloch Ellis is a good example of this approach to sex research. He is most well known for his six volume Studies in The Psychology of Sex .
(14) A major theme in Ellis’

(14) A major theme in Ellis’ 
work is the avoidance of a disease perspective as the sole explana-tion for sexual deviations. Instead of paraphilic disorders, he focused primarily on homosexuality and suggested that homosex-uality could be ‘latent’ . Since degree of ‘latency’ is a continuous variable it was possible to consider homosexuality as a dimension rather than a disease. This dimensional perspective was later exploited by Kinsey
(15) who developed his famous Kinsey scale of 
sexual orientation that rated men and women on a six point scale. Both Ellis and Kinsey shifted attention from the differences between homosexuals and heterosexuals to their similarities. In this way their work complemented research using disease or behavioural perspectives as well as the work of investigators using a fourth per-spective, which focused primarily on the individual’s ‘life story’ .
Life-story perspective

The life-story perspective is characterized by a search for the ‘meaning’ behind behaviour. This perspective appeals to the self-experienced aspect of life, so life-story perspectives tend to be very compelling and persuasive. For example, in North America, it is rare to ﬁ  nd a man with transvestic fetishism that does not recall 
being dressed as a girl for Halloween. A problem with this approach is that it is often difﬁ  cult to determine which ‘story’ is the correct 
one, or even if a single meaningful connection can be found. For example, there is no evidence that men with transvestic fetishism are more likely to have been dressed as girls when they were children than were other men. Sigmund Freud often used sexual motives to construct a life story that was difﬁ  cult to disprove. 
Freud’s research method consisted chieﬂ  y of interviewing patients 
and interpreting recurring themes in literature and art. While this

and interpreting recurring themes in literature and art. While this 
approach may seem highly susceptible to bias, it has been surpris-
ingly successful, not only for Freud but for other researchers who have adopted this method of direct interview combined with longi-tudinal follow-up, to understand the meanings of sexual acts and decisions. The explanations that individuals themselves develop to explain their behaviours are often as important and enlightening therapeutically as their ‘true’ causes.
Integration of the four perspectives
While each of the four described perspectives provide a unique basis on which to base explanatory theories about the origins of paraphilic disorders, none is mutually exclusive. In the twentieth century, some behaviourists began to acknowledge the importance 
of non-observable factors such as ‘instinct’
(16) and later, ‘motiva-

tion’ . Other theorists,(17) while recognizing the importance of 
behaviourism, emphasized that the ‘motivated behaviours’ of sleeping, eating, and mating could not reasonably be reduced to simple stimulus response associations. If motivated behaviours could not be fully explained from a single research perspective perhaps an integration of approaches would be more helpful. A good example of an integrated etiologic theory to explain para-philias is the one advanced by John Money who theorized that all children are born with the potential to develop a full range of sexual interests analogous to the observation that all healthy chil-dren at the time of birth are capable of learning to speak any human language. Which language (and by analogy which sexual interests) each child eventually expresses is determined by learning during critical periods of neurologic development.

From extensive research involving patients with genetic and 
endocrine disorders that interfered with normal anatomic and physiologic sexual development, he theorized that sometime before the onset of puberty, a ‘lovemap’ was established. He deﬁ  ned love-
map as: ‘a developmental representation or template, synchronously functional in the mind and the brain, depicting the idealized lover, the idealized love affair, and the idealized programme of sexuo-erotic activity with that lover, projected in imagery and ideation, or in actual performance’ .
(18) He hypothesized that an individual’s

(18) He hypothesized that an individual’s 
lovemap became ‘neurologically embedded’ or ‘imprinted’ , analo-gous to the way an individual’s native language becomes a ‘native tongue’ . He believed that each person has a single lovemap (analo-gous to having a single native language or ‘mother tongue’) but that each person may never be fully aware of the true nature and details of the lovemap (analogous to not learning the full vocabulary of grammar of a native language). Paraphilias represented what he termed ‘vandalized’ lovemaps resulting from an abnormal experi-ence during the ‘critical period’ during which lovemaps are formed.
While the incidence of paraphilias (especially those that involve criminal activities) in men is at least 10 times the incidence in women,
(19) the majority of both males and females do not develop 
paraphilias. In addition, unlike sexual orientation, for which there is some evidence of important genetic or at least prenatal inﬂ  u-
ences,

ences,
(20) and excluding a single retrospective report of possible 
familial co-morbidity,(21) there is no current evidence of any 
prenatal factors that cause paraphilic disorders. Similarly the hypo-thesis that being the victim of sexual abuse predisposes victims to become sex offenders has also been challenged.
(22) There is an 
increasing recognition of the fact that adolescents are capable of committing sex crimes.
(8) This edited book concluded that, 
‘approximately 20 per cent of all rapes and between 30 per cent and 50 per cent of child molestations are perpetrated by adolescent males’ . The increasing number of facilities designed to assess and treat juvenile sex offenders, male and female, supports self-report descriptions of paraphilic behaviours beginning in adolescence.
Most crimes (both sexual and non-sexual) are committed

by young adult males. One problem in assessing the literatureon the frequency of paraphilic behaviours in this age group is the frequent failure to distinguish between current paraphilic acts4.11.3 the paraphilias

SECTION 4  clinical syndromes of adult psychiatry 838
and those that are recalled. For example, it is not uncommon
for a middle-aged man with exhibitionism to recall frequentexhibitionistic activities from his youth
(2) but there is no reason
to believe that the recollections of the sexual exploits of exhi-bitionists are any more reliable than the recollections of non-paraphilic men.
T o summarize, it is often assumed that anyone who has a para-
philic interest has acted on it. In fact, the DSM-IV diagnostic criteria B requires that the interest has been acted upon or at least caused harm to someone. While cases have been described in which a person engaged in sexual activity without awareness (e.g. engag-ing in sexual acts while asleep),
(23) for the most part, thought 
precedes action. In fact, it is arguable that a person who fantasizes about paraphilic activities is more paraphilic than one who com-mits a paraphilic act while fantasizing about a non-paraphilic activity.

Most paraphilic thoughts begin around the time of puberty. 
If the ‘vandalized lovemap’ explanation of paraphilias is correct, faulty development of sexual interest likely occurs prior to puberty but is not expressed until there is sufﬁ  cient increase in sex drive for 
it to be manifested, ﬁ  rst as fantasy and later, by action.
Prognosis is an area of considerable controversy. However, 
accumulated evidence indicates that the majority of convicted sex offenders do not re-offend (likely fewer that 15 per cent). In addi-tion, evidence indicates that treatments are improving in efﬁ  cacy 
(see below).
In this section ‘treatment’ refers to intervention with intent to

In this section ‘treatment’ refers to intervention with intent to 
reduce the frequency of unwanted paraphilic symptoms. Studies on the treatment of paraphilic disorders necessarily include participants with diagnosed paraphilias who have not only sought treatment but who have also volunteered for a treatment and have at least started the treatment under study. This represents a group that for obvious reasons may be unrepresentative of the true paraphilic population, the majority of whom likely never seek treatment.
Treatment recommendations should be individualized across 
paraphilic and co-morbid disorders and to account for individual variation. For example, the treatment approach for an exhibitionist with anti-social personality disorder and heroin dependency will be very different from the treatment of a woman with paedo-
philia or an adolescent with intellectual disability and transvestic 
fetishism.

In the past half-century there have been three major innovations 
in the treatment of paraphilic disorders that have led to signiﬁ  cant 
improvement in prognosis. The ﬁ  rst of these was the use of anti-
androgen medications.
Interventions to reduce testosterone
Surgical castration has shown a high degree of success, at least in terms of reducing recidivism rates in sex offenders, with reported rates of recidivism after 30 years of follow-up as low as 2.2 per cent for convicted rapists. While this is a remarkable success rate, sur-gery for this purpose has been criticized on ethical grounds and because reversible interventions, in the form of anti-androgen medications have became available. For a review of the efﬁ  cacy of 
castration in the treatment of the sex offender.
(24)Anti-androgens administered either by mouth or by intra-
muscular injection were ﬁ  rst used in the late 1950s as an alternative

muscular injection were ﬁ  rst used in the late 1950s as an alternative 
to surgical castration. The most common oral anti-androgens prescribed for this purpose are cyproterone acetate (Androcur) (CPA) and medroy-progesterone acetate (Provera) (MPA). Both of these medications are also available in a formulation suitable for intra-muscular injection. Reviews of treatment efﬁ  cacy of both of 
these medications are also available.
(24)
A review of eight studies involving a total of 452 sex offenders 
who received treatment with MPA for between 1 and 13 years, recidivism ranged from 1 per cent to 17 per cent.
(25) Unfortunately,

(25) Unfortunately, 
anti-androgen treatment of sex offenders has been a victim of its own success. Because the success rates were so high in open studies, and because the consequences of recidivism are so great, random-ized double-blind treatment studies have been difﬁ  cult to justify 
from an ethical perspective. Gonadotropin hormone releasing hormone (GnRH) partial analogs significantly reduce serum testosterone by down-regulating receptors in the anterior pituitary resulting in a decrease in luteinizing hormone which in turn decreases production of testosterone by leydig cells in the testes. Reviews of the apparent impressive efﬁ  cacy of anti-androgens and 
GnRH analogs are available.
(26)
Selective serotonin re-uptake inhibitors (SSRIs)
Numerous reports have conﬁ  rmed the apparent efﬁ  cacy of SSRI

(26)
Numerous reports have conﬁ  rmed the apparent efﬁ  cacy of SSRI 
and related medications in the treatment of men with paraphilic disorders.
(27) Two important prescribing issues are important:
(a)  There is no evidence that the efﬁ  cacy of SSRIs in the treatment 
of paraphilic disorders is due to suppression of sex drive. Many medications that are more effective in reducing sex drive appear to have little effect on paraphilic interest.
(b)  There is no evidence that higher doses of SSRIs are more 
effective than low doses. In fact, if the prescribed SSRI causes inhibited orgasm, this may be counter-therapeutic since there is a tendency for individuals with paraphilic sexual interests to resort to paraphilic fantasies or acts in order to facilitate orgasm.
(28,29)
Psychotherapy
The evidence in support and against various psychotherapeutic interventions has recently been reviewed.
(30) Most reviews of

(28,29)
(30) Most reviews of 
psychotherapeutic interventions for paraphilic disorders focus on group therapy (the most common intervention in prisons) or individual psychotherapy (most common in private practices). However, other interventions are also important including marital therapy, family therapy, spousal therapy, occupational therapy, and substance abuse therapy.
Treatment of sex offenders based on psychologic interventions 
were carefully reviewed by a collaborative group using meta-analytic techniques.
(31) A total of 43 published studies involving a 
total of 9454 sex offenders (5078 treated and 4376 untreated) were analysed. While noting methodologic limitations, there were two important ﬁ  ndings: (i) sexual recidivism rates were lower in treated

groups (12.3 per cent) than in comparison groups (16.8 per cent) and (ii) efﬁ  cacy of psychologic treatments appear to have improved 
since the 1970s. The ﬁ  nal results of one important study were not 
included in the Hanson et al. meta-analysis. This was a longitudinal 
study with stratiﬁ  ed randomization into a group that received

839
relapse-prevention group therapy ( n = 167) or a group that did not 
(n = 225); a third group was matched to the ﬁ  rst two groups and 
consisted of sex offenders who did not volunteer to participate in the study ( n = 220). Treatment for the ﬁ  rst group consisted of 
2 years in custody, group relapse-prevention therapy followed by a 1 year mandated programme after release to the community. While results were complicated by a dropout rate in the treatment group of 27 per cent, the third group consisting of ‘non-volunteer’ controls was found to have the lowest long-term rate of sexual recidivism (19.1 per cent at 12 years follow-up). In comparison, the sub-group that entered therapy but discontinued prematurely had a 35.7 per cent sexual re-offence rate compared to the group that completed the prescribed treatment which had a 21.6 per cent sexual re-offence rate at 12 years follow-up. The ﬁ  nal conclusion of

this study was that a treatment effect for the cognitive behavioural programme did not produce a signiﬁ  cant treatment effect.
(32)
The failure to demonstrate the efﬁ  cacy of ‘relapse-prevention’ as 
it was constituted 20 years ago has been regarded by some as a major setback in the ﬁ  eld. However, the fact that even in the worst 
outcome group the majority of sex offenders were not known to have re-offended, the fact that the treatment programme under investigation was ‘manualized’ , and the fact that other important treatment interventions were not employed, makes any conclusion that sex offenders can not be treated unwarranted.Management
General principles
Summaries of management strategies for individuals with para-philic disorders and/or sex offence histories are available.
(30,33)
Speciﬁ  c recommendations for the more commonly encountered 
paraphilic disorders and for speciﬁ  c paraphilic disorders should 
also be consulted.(2) An initial approach to the management of

also be consulted.(2) An initial approach to the management of 
paraphilic disorders is summarized in Fig. 4.11.3.1.
Individuals with paraphilic disorders typically are in extreme

Individuals with paraphilic disorders typically are in extreme 
crisis when they present for treatment. It is important to assist the individual to not only understand that sexual urges are controllable but that sex acts are the person’s responsibility. This is often a sur-prise to people with paraphilias who have lived with the false belief that the difference between themselves and the rest of the world is a lack of will power. It is important to assist in maintaining and establishing a healthy social support system, ideally including family members, spouses, employers, church members, and trusted friends. Group therapy is particularly helpful in assisting to con-front cognitive distortions and in demonstrating that others not only do not re-offend but are capable of establishing healthy and 
fulﬁ lling lives. Medications can be prescribed with the aim of

fulﬁ lling lives. Medications can be prescribed with the aim of 
decreasing sexual anxiety and impulsivity (SSRIs), moderating sex drive (anti-androgens), or eliminating sex drive (GNRH 
Fig. 4.11.3.1 Management of the paraphilias.Admit to hospital and/or Report to Authorities
First priority is child safety
Admission due soley to paraphilic disorder very rareYES
Group(s)
relapse prevention
"good lives"
co-morbid addictionsMarital
education and support of spouse
enhancement of healthy sexIndividual
supportive
self esteem
current and future issuesPSYCHOTHERAPY
GNRH Analogues
base-line free testosterone, LH, FSH, glucose, weight
 baseline and yearly bone densitometry
 i.m. only but available in monthly and longer formatsAntiandrogens
available in oral and intramuscular (i.m.) formatsSelective Serotonergic Reuptake Inhibitors
avoid dosages that cause inhibed orgasmPHARMACOTHERAPY
Social Skills
enhanced non-sexual friendships

enhanced healthy sexual relationship(s)Education
literacy
sex education
work trainingCareer Counselling
financial counselling
appropriate housing
charity workREHABILITATIONTREATESTABLISH DIAGNOSE(S)
Interviews
Psychophysiologic AssessmentNOASSESS IMMEDIATE DANGER
TO SELF AND OTHERS
Is there a concern that harm will occur
Is a child at risk?4.11.3 the paraphilias

SECTION 4  clinical syndromes of adult psychiatry 840
analogues). It is vital, particularly when treating men with para-
philias who have been incarcerated, to assist them in establishing pro-social lifestyles. This includes advice about appropriate work (e.g. avoiding jobs that require contact with children in the case of paedophiles), ﬁ  nding work (some clinics maintain lists of employers 
willing to hire men they know are in treatment), and ways to spend leisure time in constructive and pro-social ways. A part of the ther-apy often neglected is the establishment of healthy sexual activities to replace the problematic sexual interests and acts for which therapy was initiated. This frequently involves marital or couple’s therapy. Some clinics establish ‘spouses’ groups to provide inde-pendent support, education, and treatment of the spouses of indi-viduals with paraphilias.
In addition, the following general principles are recommended:
(a) Identify for whom you are working

Many paraphilic disorders predispose to unconventional or criminal activities. Most countries now have mandatory reporting requirements for incidents of known or potential sexual abuse of any identiﬁ  able child. It is extremely important to establish the 
limits of conﬁ  dentiality prior to or at the ﬁ  rst meeting. Many 
clinics post a description of the rules of conﬁ  dentiality under which 
they operate. Sometimes it is difﬁ  cult to be certain for whom one 
is working. A quick rule of thumb is to ask who is paying for the work and to whom reports will be sent.
(b) Facilitate disclosure
Men and women seeking assessment and treatment for paraphilic disorders almost always think they are the ﬁ  rst (and worst) case

Men and women seeking assessment and treatment for paraphilic disorders almost always think they are the ﬁ  rst (and worst) case 
of their type ever seen. They fear they will be led from the clinic room in handcuffs and be featured on the front page of the follow-ing day’s newspaper. It is important to dispel these misconceptions not only because it will allow for a more in-depth assessment but also because it is important to dispel a ‘me-against-authority’ mentality which is common amongst individuals who see them-selves as ‘outsiders’ .
Objective measures of sexual preference (e.g. phallometric 
testing) are available.
(34) Their utility is enhanced if they are used as 
‘truth facilitators’ rather than as ‘lie detectors’ .(35) While tests based 
on deception such as surreptitious measurement of time spent viewing pictures are currently widely used, their future utility is questionable since they are valid only if the deception is effective.

Perhaps the greatest truth facilitator is scrupulous adherence 
 to disclosed rules of conﬁ  dentiality.
(c) Establish what the problem is
Typically, individuals with paraphilic disorders present in crisis.

to disclosed rules of conﬁ  dentiality.
Typically, individuals with paraphilic disorders present in crisis. 
However, the crisis often has only peripheral connection to the paraphilia. For example, a woman may have sexual masochism but seek treatment due to complications arising from major depression or substance abuse. This is true even if she insists that all her prob-lems would end if she could be cured of her masochistic interests. As reviewed above, paraphilic disorders often occur together with other psychiatric, medical, and relationship problems. Clinicians should be wary of limited differential diagnoses, especially those that attribute all problems to a single paraphilia in isolation.
(d) Identify why the patient is seeking treatment now
Most paraphilias begin in childhood or at the time of puberty. However, teenagers rarely self-present for assessment of paraphilic disorders. Therefore, most adults with paraphilic disorders may be

Most paraphilias begin in childhood or at the time of puberty. However, teenagers rarely self-present for assessment of paraphilic disorders. Therefore, most adults with paraphilic disorders may be 
assumed to be seeking treatment for a variety of reasons besides having suddenly discovered they have (for example) paedophilia. Frequent motivations include: criminal charges, discovery of prob-lematic behaviours by spouses or family members, and emergence of co-morbid problems such as depression or substance abuse.
For treatment to be successful it is very important to establish 
what the person seeking treatment thinks is the problem. Failure to do so signiﬁ  cantly reduces the likelihood of keeping the person in 
therapy, establishing a therapeutic relationship, and ultimately the prognosis for a successful outcome.
(e) Avoid one-sided treatment plans
Paraphilic disorders by deﬁ  nition involve an interaction between

Paraphilic disorders by deﬁ  nition involve an interaction between 
the most abstract and ‘high-level’ cognitive processes (sexual fantasies), limbic and sub-cortical neural pathways (sexual arousal patterns), and society. Treatment plans based on single perspectives are unlikely to succeed. Most importantly, it is vital to pay atten-tion to the worldview of the person seeking treatment. While the theory they have may be incorrect, ignoring it is likely to lead to frustration.
(f) Intervene quickly
A common mistake is to assume that because a paraphilia has been present for a long time, that it will take a long time to alleviate the symptoms. Many individuals with paraphilias think they must ﬁ  rst

review their childhood and all their previous offences before they can think about altering their current problematic behaviours. This is false. On the basis of current evidence, treatment should focus on current and future behaviours with an expectation that sexual behaviours of all types are under voluntary control. Requests to ‘taper’ problematic sexual behaviours should be dealt with as inten-tional or unintentional efforts to delay effective intervention.
(g) Be persistent
Successful treatment is not only multi-faceted but above all persistent. A useful strategy is to present treatment as a series of ‘experiments’ based on feedback about the effectiveness of inter-ventions. Treatment should be presented with the expectation of success. A review of the fact that the majority of outcome studies ﬁ nd that the likelihood of sex offenders to recidivate is less that the

likelihood of patients with major depression to have a recurrence of their life-threatening illness, is often an inspiring surprise to people entering therapy.
(h) Be inclusive with treatment
Begin with a thorough assessment and consideration of a complete differential diagnosis. If there are indications of co-morbid problems (e.g. foetal alcohol syndrome, genetic disorders, mood disorders, psychotic disorders, personality disorders, etc.) further investigations and interventions should proceed without delay. Once a diagnosis has been made, all the treatment options should be reviewed with the person seeking treatment (see above). Risks and beneﬁ  ts of treatment options (including the risk of declining treat-

ment) should be thoroughly reviewed. Choice of treatment should be a collaboration between the clinician and person seeking treatment, but ultimately should be informed and voluntary. Typically treatment should include both individual and group psychotherapy. If the person has a sexual partner, couple’s therapy is often of assistance. Pharmacologic treatment can include SSRIs

841
(often more effective at doses used for depression as opposed to the 
higher doses used for obsessive–compulsive disorder), anti-androgens and/or GnRH analogues. Acceptance of treatment with anti-androgens is increased by explaining that treatment effects are reversible. More information about treatment options is available.
(2)
(i) Be optimistic
The frequency of sex offences is dropping. The effectiveness of 
treatment of sex offenders (who are not necessarily paraphilic) is improving. Sex offender re-offence rates are below 15 per cent. New as well as established treatments are available.
Beyond eliminating criminal and harmful sexual behaviours, 
a key to successful therapy is the establishment of non-criminal and beneﬁ  cial sexual interests and behaviours. Remarkably, the

a key to successful therapy is the establishment of non-criminal and beneﬁ  cial sexual interests and behaviours. Remarkably, the 
literature on treatment of paraphilic disorders almost completely ignores the concept of establishing non-paraphilic sexual behav-iours as a treatment goal. This is a mistake. Adult men and women rarely want to ‘give up’ sex. However, if they are provided with the opportunity to improve their sex lives they frequently become enthusiastic (and successful) participants.
Dr Fedoroff gratefully acknowledges Drs J. Bancroft, F. Berlin, J. Bradford, E. Coleman, P . Fagin, R. Rosen, and the late J. Money for their signiﬁ  cant inﬂ  uences on his thinking about the paraphil-
ias. However, none should be held responsible for any of the opin-ions expressed in this chapter.
Web sites
Robert Hare Psychopathy Web site: http://www.hare.org/

Web sites
Magnus Hirschfeld Archive for Sexology: http://www2.hu-berlin.de/
sexology/
Kinsey institute: http://www.indiana.edu/~kinsey/
Useful summaries
Bancroft, J. (in press). Human sexuality and its problems . Elsevier Health 
Sciences In Pr ess.
Love, B. (1999). Encyclopedia of unusual sex practices . Greenwich Editions, 
London.
Money, J. (1986). Venuses penuses . Prometheus Books, Buffalo, New Y ork.
Francoeur, R.T. and Noonan, R.J. (eds.) (2004). The continuum complete 
international encyclopaedia of sexuality . Continuum, New Y ork.
Schwartz, B.K. (ed.) (1995–2005). The sex offender  (Vols. 1–5). Kingston, 
New Jersey.
 1. Fedoroff, J.P . (in press). Sadism, sadomasochism, sex and violence. 
Canadian Journal of Psychiatry .

 2. Fedoroff, J.P . (2003). Paraphilic worlds. In Handbook of clinical sexuality 
for metal health professionals  (ed. S.B. Levine). Brunner/Routeledge, 
New Y ork.
 3. Coleman, E. (2005). Neuroanatomical and neurotransmitter 
dysfunction and compulsive sexual behavior. In Biological substrates of 
human sexuality  (ed. J.S. Hyde), pp. 147–69. American Psychological 
 4. Hingsburger, D., Grifﬁ  ths, D., and Quinsey, V . (1991). Detecting 
counterfeit deviance: differentiating sexual deviance from sexual inappropriateness. Habilitative Mental Healthcare Newsletter , 51–4. 5. Cantor, J.M., Blanchard, R., Robichaud, L.K., et al. (2005). Quantitative 
reanalysis of aggregate data on IQ in sexual offenders. Psychological 
Bulletin ,131, 555–68.
 6. Lalumière, M., Harris, G.T., Quinsey, V ., et al. (2005). The causes of rape .

American Psychological Press, Washington, DC.
 7. Diamond, M. and Uchiyama, A. (1999). Pornography, rape and sex 
crimes in Japan. International Journal of Law and Psychiatry ,22, 1–22.
 8. Barbaree, H. and Marshall, W.L., (eds.) (2005). The juvenile sex offender
 9. McHugh, P .R. and Slavney, P .R. (1983). The perspectives of psychiatry .
10. Krafft-Ebing, R.V . (1906). Psychopathia sexualis. A medico-forensic 
study, with especial reference to the antipathic sexual instinct .
Physicians and Surgeons Book Company, New Y ork.
11. Brautigam, W. (1977). Die angliche Beurtelung in Psychopathologie der 
Sexualitae. In (eds. H. Grese and F. Stutgart).
12. Hirshﬁ  eld, M. (1910). Die Transvestiten. A. Pulvermacher, Berlin.

13. Moll, A. (1983). Untersuchungen uber die Libido Sexualis. 
In Freud, biologist of the mind  (ed. F.J. Sulloway), p. 304. Basic Books, 
New Y ork.
14. Ellis, H. (1936). Studies in the psychology of sex . New Y ork.
15. Kinsey, A.G., Pomeroy, W.B., and Martin, C.E. (1948). Sexual behavior 
in the human male . Saunders, Philadelphia.
16. Darwin, C.R. (1859). On the origin of species by means of natural 
selection, or, the preservation of favored races in the struggle for life . John 
Murray, London.
17. Lashley, K.S. (1938). The experimental analysis of instinctive behavior. 
Psychology Review ,45, 445.
18. Money, J. and Lamacz, M. (1989). Vandalized lovemaps: paraphilic 
outcome of seven cases in pediatric sexology . Prometheus Books, 
Amherst, NY.

19. Fedoroff, J.P ., Fischell, A., and Fedoroff, B. (1999). A case series of 
women evaluated for paraphilic sexual disorders. The Canadian Journal 
of Human Sexuality ,8, 127–40.
20. Blanchard, R. and Bogaert, A.F. (1996). Homosexuality in men 
and number of older brothers. The American Journal of Psychiatry ,
153, 27–31.
21. Gaffney, G.R., Lurie, S.F., and Berlin, F.S. (1984). Is there familial 
transmission of pedophilia? The Journal of Nervous and Mental Disease ,
172
, 546–8.
22. Fedoroff, J.P . and Pinkus, S. (1996). The genesis of pedophilia: testing 
the abuse to abuser hypothesis. Journal of Offender Rehabilitation ,
23, 85–101.
23. Shapiro, C.M., Trajonovic, N.N., and Fedoroff, J.P . (2003). Sexomnia-a 
new paraphilia? Canadian Journal of Psychiatry ,48, 311–7.

24. Bradford, J. (1987). Medical interventions in sexual deviance. In Sexual
deviance  (eds. D.R. Laws and W. O’Donohue), pp. 449–64. The Guilford 
25. Grossman, L.S., Martis, B., and Fichtner, C.G. (1999). Are sex
offenders treatable? A research overview. Psychiatric Services ,50,
349–61.
26. Bradford, J.M.W. (2001). The neurobiology, neuropharmacology and 
pharmacologic treatment of the paraphilias and compulsive sexual 
behaviour. Canadian Journal of Psychiatry ,46, 26–34.
27. Greenberg, D.M and Bradford, J.M.W. (1997). Treatment of the 
paraphilic disorders: a review of the role of selective serotonin reuptake inhibitors. Sexual Abuse: A Journal of Research and Treatment ,
9, 349–60.
28. Fedoroff, J.P . (1994). Serotonergic drug treatment of deviant sexual 
interests. Annals of Sex Research ,6, 105–17.

9, 349–60.
29. Fedoroff, J.P ., Peyser, C., Franz, M.L., et al. (1994). Sexual disorders 
Neurosciences ,6, 147–53.
30. Marshall, W.L., Marshall, L.E., Serran, G.A., et al. (2006). Treating 
sexual offenders . Routledge, New Y ork.4.11.3 the paraphilias

SECTION 4  clinical syndromes of adult psychiatry 842
31. Hanson, R.K., Gordon, A., Harris, A.J.R., et al. (2002). First report 
of the collaborative outcome data project on the effectiveness of psychological treatment of sex offenders. Sexual Abuse: A Journal of 
Research and Treatment ,27, 169–95.
32. Marques, J.K., Weideranders, M., Day, et al. (2005). Effects of a 
relapse prevention program on sexual recidivism: ﬁ  nal results from 
California’s Sex Offender Treatment and Evaluation Progject(SOTEP). Sexual Abuse: A Journal of Research and Treatment ,17,
79–107.
33. Laws, D.R. and O’Donohue, W. (eds.) (1997). Sexual deviance: theory, 
assessment, and treatment . The Guilford Press, New Y ork.
34. Fedoroff, J.P ., Kuban, M., and Bradford, J. (in press). Laboratory 
measurement of penile response in the assessment of sexual interests. 
In Sex offenders: a multi-disciplinary approach to identiﬁ  cation, risk 
assessment, treatment and legal issues  (eds. F. Saleh, J. Bradford,

A. Grudzinskas, and D. Brodsky). Oxford Press, New Y ork.
35. Grubin, D. (in press). Using the polygraph to manage risk in sex 
offenders. In Assessment and treatment of sexual offenders: a
handbook  (eds. A.R. Beech, L.A. Craig, and K.D. Browne). Wiley,
London.
4.11.4 Gender identity 
disorder in adults
History
The behavioural phenomenon of transsexualism (now gender 
identity disorder) is ancient. It has been recorded for centuries and in a broad range of cultures.
(1) The historic behavioural picture is 
comparable to that seen clinically.
In the ﬁ  rst half of the twentieth century medical reports of sex 
reassignment surgery were described in Europe, primarily in Switzerland.
(2) In the 1930s a wide-selling biography Man into 
Woman  described a Dutch painter who underwent surgical sex

Woman  described a Dutch painter who underwent surgical sex 
reassignment.(3) Contemporary interest in transsexualism surged 
in 1952 when George Jorgensen, an American, travelled to Denmark and underwent hormonal and surgical treatment to become Christine Jorgensen.
(4) The resultant international publicity yielded 
hundreds of people worldwide applying to the Danish doctors for similar treatment.
(5)
By the mid-1960s there were surgeons scattered in several coun-
tries performing sex reassignment. Then in the United States at the 
Johns Hopkins Hospital and the University of Minnesota Hospitals 
and in the United Kingdom at Charing Cross Hospital, compre-
hensive sex reassignment programmes commenced. Extensive 
publicity was given to the Johns Hopkins programme as initially 
reported in the New York Times  in 1966. It described the rationale

reported in the New York Times  in 1966. It described the rationale 
for the programme and in the words of its director, ‘if the mind cannot be changed to ﬁ  t the body, then perhaps we should consider 
changing the body to ﬁ  t the mind’ .
(6)
In 1966 the ﬁ  rst professional text on transsexualism was written 
by Harry Benjamin, widely acknowledged as the ‘father of trans-sexualism’ .
(7) In 1969 the ﬁ  rst multidisciplinary text was edited by 
the author and John Money.(6) During the past 35 years the recog-
nition of transsexualism, or gender identity disorder, as a treatable condition requiring psychiatric, endocrine, and surgical interven-
tion has been accepted.
The prevalence of gender identity disorder in adults is estimatedfrom a comprehensive appraisal in the Netherlands at 1 in 10 000 males and 1 in 30 000 females.

(8) At nearly all clinical centres the ratio 
of male-to-female patients ranges from 3:1 to 4:1, in favour of males. In some East European centres the ratio is 1:1 or reversed.
(9)
Diagnosis
Diagnostic criteria of gender identity disorder in adults in DSM-IVTR
(10) include a stated desire to be the other sex, a desire to live 
and be treated as the other sex, or the conviction that he or she has the typical feelings and reactions of the other sex. There is a preoccupation for removal of primary and secondary sexual char-acteristics and for procedures to alter physically the sexual charac-teristics to simulate the other sex. The condition is not associated with physical intersex. ICD-10 diagnostic criteria are similar but there is no mention of intersex exclusion.
(11)
Origins

(11)
Origins
The search for the origins of transsexualism continues with an 
increasing bias towards those that are physiological. Some 20 years ago there was a false prophet in the guise of the HY antigen, on 
the Y chromosome believed to be inﬂ  uential in the development of 
the testes. A series of male transsexuals were found to be lacking this antigen and the tentative conclusion reached was that its absence resulted in a failure to masculinize the brain in the direc-tion of a male identity.
(12) However, the author’s collaborative 
effort to replicate that study was not successful as all the male trans-sexuals studied appeared to have normal HY antigen.
(13)
A more recent ﬁ  nding from the Netherlands implicates the brain 
region known as the bed nucleus of the stria terminalis. In a series of six male transsexuals studied at post-mortem over a 10-year period the size of the nucleus was comparable to that of typical females and not males.

(14) A criticism of this study is that the long-
term oestrogen treatment for these males may have altered the size of the nucleus. In response the researchers argue that males treated with anti-male hormone drugs or oestrogen for prostate cancer do not have an alteration in the nucleus size from typical males. However, this treatment may not be comparable to that given to transsexuals. Another criticism is that the sex difference in size of the nucleus does not manifest until early adulthood whereas the symptoms of GID often manifest earlier.
Research with male transsexuals has revealed what might be 
indirect markers reﬂ  ecting biological distinctions. In agreement 
with other researchers’ ﬁ  ndings that male homosexuals have a 
greater likelihood of having older brothers,
(15) our homosexually 
oriented male transsexuals also have more older brothers.(16)
A theory behind this ﬁ  nding is that there is a progressive immuni-

zation with each pregnancy by the pregnant mother against the male foetus reﬂ  ecting antigenicity of the Y chromosome. This 
would disrupt typical male development.
A higher ratio of aunts to uncles on the mother’s side has also 
been found in our male transsexuals
(17) a finding previously

843
reported by another researcher for male homosexuals.(18) A theory 
here is that a semilethal factor has been operant in one generation (against uncles) that in the subsequent generation inﬂ  uences brain 
development resulting in an atypical behavioural pattern (homo-sexual or transsexual development). The ﬁ  nding is explainable with 
genomic imprinting where a gene can be dormant in one genera-tion depending on which parent transmitted it.
(17)
We also ﬁ  nd that both male and female transsexuals are more 
often non-right-handed.(19) Hand use preference begins in utero 
and may reﬂ  ect hormonal levels or cerebral dysfunction.
For female transsexuals, a series of reports indicates a higher 
rate of polycystic ovarian disease.(20) Although such women secrete 
higher levels of androgen th an typical females in ad ulthood, prenatal

higher levels of androgen th an typical females in ad ulthood, prenatal 
levels are unstudied. However, nearly all patients with polycystic ovarian disease are not transsexual and most female transsexuals do not have polycystic ovarian disease.
Treatment
There have been no randomized controlled trials of treatment and clinical management has evolved from decades of experience.
Prior to recognition of transsexualism as a disorder deserving 
medical and psychiatric attention many patients self-mutilated or committed suicide
(7) Transsexual patients are helped by sympa-
thetic assessment and intervention. However, transsexuals can be difﬁ cult patients to treat. It is a rare disorder in which patients

thetic assessment and intervention. However, transsexuals can be difﬁ cult patients to treat. It is a rare disorder in which patients 
make their own diagnosis, ‘I am transsexual’ , and prescribe their own treatment, ‘I want sex-change hormones and surgery’ . Patients can be demanding and impatient for the therapist’s acquiescence. They may be resentful for having to see a psychiatrist, holdingthe opinion that the desire for hormonal treatment and surgery should be sufﬁ  cient, and psychiatric agreement should be unneces-
sary. Some patients will threaten self-mutilation or suicide iftheir demands and time schedules for demands are not met. Patients need to know that psychological stability is a key ingredi-ent to successful negotiation of the cross-gender living trial period ‘Real Life Experience’ (see below) and recommendation for
surgery, and that suicidal behaviour is a contraindication to going 
forward.

forward.
The general psychiatrist should take a full psychosexual history 
with emphasis on the onset and development of the gender dys-phoria, attempts at treatment, and the patient’s long-term goals and appreciation of the obstacles to be confronted. General psychi-atric and medical status needs to be understood. A referral is to be made to a specialist centre.
During the past 30 years medical doctors and psychologists 
specializing in the treatment of transsexualism have worked to develop effective intervention strategies. Early on there was some optimism that extensive, prolonged psychotherapy could modify the patient’s gender identity to conform to the patient’s birth sex. However, in the vast majority of cases, this was not possible.
During the past 20 years one project undertaken by the Harry

During the past 20 years one project undertaken by the Harry 
Benjamin International Gender Dysphoria Association, the professional body dedicated to the study and treatment of trans-sexualism, has been setting an extensive series of requirements for evaluation and treatment of gender identity disordered people. This set of guidelines is known as the Standards of Care .
(21) Their 
principal purpose is to assure that people presenting with dissatis-faction continuing to live in the sex role to which they were born undergo comprehensive psychiatric and other medical evaluation

principal purpose is to assure that people presenting with dissatis-faction continuing to live in the sex role to which they were born undergo comprehensive psychiatric and other medical evaluation 
and enter into an appropriate treatment programme. The pro-gramme includes, in addition to ongoing psychiatric or psycho-logical monitoring, possibly endocrine therapy and, depending on the outcome of the graduated trial period of cross-gender living, possibly sex reassignment surgical procedures. The philosophy of treatment is to do reversible procedures before those that are irreversible. Thus, clothing change, name change, and cross-gender role socialization, would precede endocrine treatment with its gradual somatic changes, followed, in carefully selected cases, by surgical treatment.
The screening and evaluation of patients given the opportunity 
to demonstrate that they will beneﬁ  t from cross-gender living,

to demonstrate that they will beneﬁ  t from cross-gender living, 
perhaps culminating in surgical treatment, is known as the ‘Real Life Experience’ . This requires that patients live full-time for at least a year and preferably 2 years in that role. The experience includes high doses of cross-sex hormones and full-time employment or full-time student status in the new role for at least a year. If patients can demonstrate to themselves and mental health experts that they have successfully negotiated the ‘Real Life Experience’ and are adjusting better in this new gender role, they can be referred for surgery.
Hormonal effects
Response to hormonal treatment is variable. This is particularly notable and potentially problematic for males. As with people born female, breast development spans a continuum. Patients may 
erroneously believe that more oestrogen will result in greater breast

erroneously believe that more oestrogen will result in greater breast 
development. They neglect the fact that people born female have 
quite adequate female hormone production but the limiting 
factor is tissue response. In addition to breast development, male patients report increased hip and buttock fat, skin softening, and 
loss of sex drive and erection capacity. Vocal retraining is required and perhaps surgical alteration of the larynx to effect a woman’s voice. Facial hair removal is required. Some patients opt for major facial contour reconfiguration, performed by a few cosmeticsurgeons.
Androgen treatment to the female results in voice deepening, 
facial hair growth, general body hair growth, menses cessation, clitoral hypertrophy, and increased sex drive. T estosterone effects are very pronounced. The deepening voice and beard growth and perhaps scalp hair loss can metamorphose the female’s appearance dramatically.
Surgery

Surgery
Genital surgical treatment for the male includes penectomy, orchidectomy, and creation of a neovagina. The neovagina may be created from penile skin, perhaps augmented by other skin, or from a portion of large intestine.
(22) The cosmetic result is usually 
very good. The extent of sexual responsivity with the neovagina is mainly anecdotal. Many patients report the subjective experience of orgasm but describe it in a different form from that experienced prior to surgery as a male. Very few physiological measures of the sexual response cycle have been reported with postoperative trans-sexual patients.
(23)
Female transsexuals undergo bilateral mastectomy, and usually 
hysterectomy and ovariectomy. Genital surgery is an option taken 4.11.4 gender identity disorder in adults

SECTION 4  clinical syndromes of adult psychiatry 844
by perhaps half because of the limitations of phalloplasty. Two 
major approaches are utilized. One is creation of a micropenis from the androgen enlarged clitoris with relocation of the urethra to enable micturition while standing. Prosthetic testes can be incor-porated into the labia sutured together. The microphallus will not permit vaginal penetration for intercourse but is erotically 
sensitive.
(24) Alternatively, phalloplasty involves major surgical 
interventions with scarring at donor sites, particularly the arm.(25)
The neophallus is not as close cosmetically to a natural penis as some patients want. It can be made more rigid with an inﬂ  atable 
implant and a conduit for urine may be surgically created. A proce-dure anastomosing a nerve from the arm to that enervating the clitoris offers promise of erotic sensation along some of the neophallus.
Sex reassignment outcome

Follow-up reports on operated transsexuals are generally quite favourable. An early review of several follow-up studies,
(26)
reported on 283 male-to-female transsexuals. Results were judged satisfactory for 71 per cent, uncertain for 17 per cent, and unsatis-factory for 12 per cent. For 83 female-to-male transsexuals results were judged satisfactory for 81 per cent, uncertain for 13 per cent, 
and unsatisfactory for 6 per cent. A more recent report considered 
reassignment successful in 46 of 50 male-to-female transsexuals 
and successful in all 61 female-to-male transsexuals.
(27) In another 
study, of 55 male-to-female transsexuals, none regretted surgery and none had signiﬁ  cant doubts regarding their reassignment 
status as women. Of 25 female-to-male transsexuals, at least 90 per cent were judged successful.
(28) In a review of the English language

(28) In a review of the English language 
literature over a 10-year period for operated transsexuals, 90 per cent of male-to-female transsexuals were judged to be satisfactory and 95 per cent of female-to-male transsexuals were similarly judged successful.
(29) The criteria for success in some studies 
include objective measures of psychological and vocational status, in others the criterion is limited to an absence of regret over the reassignment process.
One study is notable because it effected some randomization of 
treatment conditions.
(30) It was reported on 40 male-to-female 
transsexuals approved for surgery at Charing Cross Hospital, London. As patients qualiﬁ  ed for surgery they were randomly

transsexuals approved for surgery at Charing Cross Hospital, London. As patients qualiﬁ  ed for surgery they were randomly 
assigned to two groups. Half were operated on in 3 months and the other half were kept on a waiting list for about 2 years. All patients completed a standardized assessment at acceptance for surgery and at the end of 2 years. The group that received the earlier surgery showed signiﬁ  cant improvement in a range of psychometric meas-
ures and maintained employment. The unoperated group showed no improvement in psychological testing and deteriorated in employment.
Family management

Transsexual patients are often married and have children. When possible, the family should become part of the treatment process. Typically relations are strained with the marital partner of the transsexual and divorce is usual. Particularly when children are involved an effort should be made to deal with the feelings of betrayal or abandonment from the transsexual’s spouse that con-taminate the continuing relationship between transsexual parent and children. Often there is concern by the parents that the patient’s 
transsexualism will impact adversely on the children. There is con-cern speciﬁ  cally in areas of gender identity of the children and peer

transsexualism will impact adversely on the children. There is con-cern speciﬁ  cally in areas of gender identity of the children and peer 
group reactions to the knowledge that one of their age mate’s par-ents is transsexual. However, in the author’s research of 34 children of transsexuals who were living with or in regular contact with the transsexual parent, there were no instances of gender identity disorder in the children and no instances of peer group alienation that were especially problematic.
(31) Children typically have many 
questions about the transsexual transformation of that parent that can be answered by the clinician, perhaps with the transsexual present.
The third sex

A recent development in the pattern of patients presenting clini-cally are those with a transgendered identity, popularly known as ‘the third sex’ . These males or females do not request ‘sex change’ . Rather, they want, if male, to be demasculinized and, if female, to be defeminized. Thus males may want castration and penectomy but no oestrogen treatment and no vagina, and females may want mastectomy, perhaps hysterectomy, but no androgen treatment and no phallus.
These patients pose a dilemma for clinicians. The crux of patient

These patients pose a dilemma for clinicians. The crux of patient 
management for gender identity disorder is the ‘Real Life Experience’ (see above), including cross-sex hormonal treatment, the prelude to possible surgical alteration. Reversible procedures precede those that are irreversible in this management strategy.But with third-sex patients, no ‘Real Life Experience’ is possible. They do not have a trial period. Guidelines for testing the ration-
ality and stability of their requests need to evolve from the bodyof clinicians currently attempting management of this unique
population.
Transsexual patient subgroups

Professionals not experienced in the treatment of large numbers of male-to-female transsexual patients are often unaware that a sub-stantial minority, perhaps a third, are not sexually oriented to male partners. Many of these patients have been married and are fathers, and many will be bisexual or remain sexually attracted to females only after surgery and live as lesbian women. A much smaller num-ber of female-to-male transsexuals are sexually attracted to male partners and live as gay men after reassignment surgery.
In addition to the subtypes of transsexuals based on their sexual 
orientation, some male transsexual patients evolve through a diag-nostic phase more closely ﬁ  tting fetishistic transvestism. These

orientation, some male transsexual patients evolve through a diag-nostic phase more closely ﬁ  tting fetishistic transvestism. These 
patients have been more masculine in general lifestyle and appear-ance than other male transsexuals, cross-dressing has been sexually arousing, and they have usually been heterosexually oriented. 
However, with the passage of time gender dysphoria increases and 
fetishistic components of cross-dressing diminish or disappear. Many have been sexually aroused by fantasies of themselves as women.
(32) They have been termed ‘autogynephiles’ . There is some 
evidence that males evolving through a fetishistic cross-dressing phase, presenting as somewhat older at gender identity clinics, have a poorer prognosis after surgery. However, it is primarily the progression through the ‘Real Life Experience’ that becomes the critical management guideline for patients, irrespective of their background.

845
Gender identity as a disorder
A growing movement among transsexual people argues for removal 
of gender identity disorder from the psychiatric and medical lists of disorders or diseases. These advocates argue that their sexual iden-tity is normal male or female and that surgical correction of their 
anatomical anomaly is all that is required to allow them to 
live as normal men or women. Their condition is depicted as dis-tinctive from the recognized traditional forms of mental disorder such as schizophrenia or major depression. Furthermore, carrying a psychiatric diagnosis is stigmatizing. One argument for inclusion of transsexualism in the APA diagnostic manual of disorders is that it follows the criteria of other entries, that is subjective distress and social disadvantage. Another considers third-party payment for treatment. It is unlikely that medical insurance carriers, private or governmental, would fund intervention for a non-medical condition.

Additionally, there is objection by some persons with gender 
identity disorder to being referred to as transsexual. They prefer the designation ‘transwoman’ for what has been known as male-to-female transsexualism, and ‘transman’ for female-to-male trans-
sexualism.
Legal issues
Cultural and legal approaches to transsexualism vary widely across nations and cultures. They are beyond the scope of this chapter. 
However legal issues in the United States and United Kingdom can be summarized as follows.
Part of the ‘Real Life Experience’ of cross-gender living includes 
employment in the desired gender role. However, transsexuals may be the object of employment discrimination based on their trans-sexualism. In the United States, transsexuals were denied federal protection 20 years ago when the court held that the anti-sex discrim-ination statute protected men and women, but not transsexuals.
(33)
Finally, in 2004, another federal court extended employment pro-tection.

(33)
(34) In the United Kingdom, in 1997, a ruling on an English 
case before the European Court of Justice held that anti-sex discrimination law, to which all European Union members were subject, did include transsexuals. Thus discrimination in employ-ment was illegal.
(35)
Changing sex on one’s birth certiﬁ  cate can be an important 
step in the life of the postoperative transsexual. In its absence, the person’s legal sex may remain in the preoperative status, and pose obstacles to a full life. Marriage is a key issue. In the United Kingdom, until recently, postoperative transsexuals could not have a new birth certiﬁ  cate issued and change their legal sex. Thus a 
male-to-female transsexual could not marry a male and a female-to-male transsexual could not marry a female. This changed in a statute enacted in 2004.
(36) In the United States most states permit

(36) In the United States most states permit 
some birth certiﬁ  cate change. However, that change may not be 
recognized in another state.
Barrett, J. (ed.) (2008). Transsexual and other disorders of gender identity .
Radcliffe Publishing, Oxford.
Ettner, R., Monstrey, S., and Eyler, E. (eds.) (2008). Principles of 
transgendered medicine and surgery . Haworth Press,
Binghampton.References
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cross-cultural aspects. In Appendix to The transsexual phenomenon
(ed. H. Benjamin). Julian Press, New Y ork.
 2. Abraham, F. (1931). Genital alteration in two male transvestites. 
Zeitschrift Sexualwissenschaft ,18, 223–6.
 3. Hoyer, N. (1933). Man into woman: an authentic record of a change of 
sex. E.P . Dutton, New Y ork.

 4. Hamburger, C., Sturup, G., and Dahl-Iversen, E. (1953). Transvestism: 
hormonal, psychiatric and surgical treatment. The Journal of the 
American Medical Association ,12, 391–6.
 5. Hamburger, C. (1953). The desire for change of sex as shown by 
personal letters from 465 men and women. Acta Endocrinologica ,
14, 361–75.
 6. Green, R. and Money, J. (eds.) (1969). Transsexualism and sex 
reassignment . Johns Hopkins Press, Baltimore, MD.
 7. Benjamin, H. (1966). The transsexual phenomenon . Julian Press, 
New Y ork.
 8. Kesteren, P ., Gooren, L., and Megens, J. (1996). An epidemiological 
and demographic study of transsexuals in The Netherlands. Archives of 
Sexual Behavior ,25, 589–600.
 9. Godlewski, J. (1988). Transsexualism and anatomic sex ratio reversal in 
Poland. Archives of Sexual Behavior ,17, 547–8.

10. American Psychiatric Association. (2000). Diagnostic and statistical 
11. World Health Organization. (1992). International statistical 
12. Eicher, W., Spoljar, M., Cleve, H., et al. (1979). H-Y antigen in trans-
sexuality. Lancet ,2, 1137–8.
13. Wachtel, S., Green, R., Simon, N., et al. (1986). On the expression 
of H-Y antigen in transsexuals. Archives of Sexual Behavior ,
15, 49–66.
14. Zhou, J., Hoffman, M., Gooren, L., et al. (1995). A sex difference in
the human brain and its relation to transsexuality. Nature ,
378, 68–70.
15. Blanchard, R. (1997). Birth order and sibling sex ratio in homosexual

15. Blanchard, R. (1997). Birth order and sibling sex ratio in homosexual 
versus heterosexual males and females. Annual Review of Sex Research ,
8, 27–67.
16. Green, R. (2000). Birth order and ratio of brothers to sisters in 
transsexuals. Psychological Medicine ,30, 789–95.
17. Green, R. and Keverne, E.B. (2000). The disparate maternal 
aunt–uncle ratio in male transsexuals: an explanation invoking 
genomic imprinting. Journal of Theoretical Biology ,202, 55–63.
18. Turner, W. (1995). Homosexuality, type 1: an Xq 28 phenomenon. 
Archives of Sexual Behavior ,24, 109–34.
19. Green, R. and Y oung, R. (2001). Hand preference, sexual preference, 
and transsexualism. Archives of Sexual Behavior ,30, 565–74.
20. Futterweit, W., Weiss, R., and Fagerstrom, R. (1986). Endocrine 
evaluation of 40 female-to-male transsexuals: increased frequency of polycystic ovarian disease in female transsexualism. Archives of Sexual

evaluation of 40 female-to-male transsexuals: increased frequency of polycystic ovarian disease in female transsexualism. Archives of Sexual 
Behavior ,15, 69–78.
21. Harry Benjamin International Gender Dysphoria Association. 
(1981). The standards of care for gender identity disorder . Symposion, 
Düsseldorf.
22. Schrang, E. (1998). Male-to-female feminizing genital surgery. 
In Current concepts in transgender identity  (ed. D. Denny), pp. 315–33. 
Garland, New Y ork.
23. Green, R. (1998). Sexual functioning in post-operative transsexuals. 
International Journal of Impotence Research ,10(Suppl. 1), 22–4.
24. Hage, J. and van Turnhout, A. (2006). Long-term outcome of 
metaidoiplasty in 70 female-to-male transsexuals. Annals of Plastic 
Surgery ,57, 312–16.4.11.4 gender identity disorder in adults

SECTION 4  clinical syndromes of adult psychiatry 846
25. Monstrey, S., Hoebeke, P ., Dhont, M., et al. (2005). Radial forearm 
phalloplasty, review of 81 cases. European Journal of Plastic Surgery ,
28, 206–12.
26. Pauly, I. (1981). Outcome of sex reassignment surgery for transsexuals. 
Australian and New Zealand Journal of Psychiatry ,15, 45–51.
27. Blanchard, R., Steiner, B., Clemensen, L., et al. (1989). Prediction of 
regrets in postoperative transsexuals. Canadian Journal of Psychiatry ,
34, 43–5.
28. Kuiper, B. and Cohen-Kettenis, P . (1988). Sex reassignment surgery. 
A study of 141 Dutch transsexuals. Archives of Sexual Behavior ,
17, 439–57.
29. Green, R. and Fleming, D. (eds.) (1991). Transsexual surgery follow up: 
status in the 1990s. In Annual review of sex research  (eds. J. Bancroft, 
C. Davis, and D. Weinstein). Society for the Scientiﬁ  c Study of Sex, 
Mount Vernon, IA.30. Mate-Cole, C., Freschi, M., and Robin, A. (1990). A controlled study

Mount Vernon, IA.30. Mate-Cole, C., Freschi, M., and Robin, A. (1990). A controlled study 
of psychological and social change after surgical gender reassignment in selected male transsexuals. The British Journal of Psychiatry ,
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Transgenderism ,2, 1–7.
32. Blanchard, R. (1989). The classiﬁ  cation and labelling of non-
homosexual gender dysphorics. Archives of Sexual Behavior ,18, 315–34.
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discrimination and the criteria of sex. Yale Law and Policy Review ,
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34. Smith,v. City of Salem. (2004). 378 F.3d 566 (6th Cir.)35. P v. S and Cornwall County Council. (1996). ECRI-2143 C-13/94.
36. Gender Recognition Act. (2004).

4.12
4.12.1 Personality disorders: 
an introductory perspective
The goal of psychiatry is the study of mental illnesses. In this 
chapter we consider the degree to which personality disorders can be considered as mental illnesses.
Basic notions
Personality is the quality that makes each one of us both different from others and consistently recognisable throughout our lives. Hence, there are two approaches to study personality. One istransversal, consisting on description of archetypes of human beings. One of the ﬁ  rst to take this approach was Theophrastus (372–287/5 
BC) who in his book The Characters , portrays thirty-two such proto-
types. Some of them can be are easily recognized by present-day
psychiatrists, for instance those typiﬁ  ed by poor impulse control: 
The offensive man ( bdeluria ), the unsociable man ( authadeia ),
the show-off ( alazoneia ) and the slanderer ( kakologia ); by obsessive

the show-off ( alazoneia ) and the slanderer ( kakologia ); by obsessive 
traits: the superstitious man ( deisidaimonia ) or by paranoid
traits: the suspicious man ( apistia ). The corresponding contempo-
rary approach consists of the isolation of psychological traitsor dispositions, to describe permanent inclinations to behave in a preset way.
The longitudinal approach to the study of the personality is 
based on the notion that there is an initial seed that develops through the lifetime. Sir Francis Galton (1822–1911) was among the ﬁ  rst to consider the inheritance of individual differences in 
humans, although for centuries breeders of dogs, horses or bulls for bullﬁ  ghting, had been selecting animals for mating on to select 
desired characteristics whether is be hunting, running or ﬁ  ghting.
Twin and developmental studies have been used. For example, 
The ‘New Y ork Longitudinal Study’
(1) on infant temperament

(1) on infant temperament 
started in the early 1950s and examined how temperament inﬂ uences adjustment throughout life. Kagan et al.
(2) followed up 
a cohort of babies to age 14-17 years and reported that those who were highly reactive when they were babies were more likely to be ‘subdued in unfamiliar situations, to report a sour mood and anxiety over the future and to be more religious’ .
There are two key features of personality, one of which is 
temperament and the other character. The two together constitute personality.
T emperament  is the innate predisposition to behave in a partic-
ular manner. Historically the concept was part of the theory of
the four humours, which had corresponding temperaments:sanguine  (the individual is led by his own pleasure to live), choleric

(the individual has a feeling of power and shows it), melancholic
(the individual is dominated by doubts and ruminations) and phlegmatic  (the individual lacks any links to life, lives without effort 
nor pleasure). Current research on the biological basis of personal-
ity has renewed the interest in temperament.
Character  is a conﬁ  guration of habits, a disposition, consisting 
in the actualised aspects acquired through learning and shaped by experience.Contents
4.12.1 Personality disorders: an introductory
perspective
 4.12.2 Diagnosis and classiﬁ  cation of personality
disorders
 4.12.3 Speciﬁ  c types of personality disorder
 4.12.4 Epidemiology of personality disorders

disorders
abnormal personalities: from genes to biodevelopmental pathways
 4.12.6 Psychotherapy for personality disorder
 4.12.7 Management of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 848
Psychiatry and abnormal behaviours
Descriptions of individuals with behavioural characteristics of 
a negative moral or social value exist in every culture and most societies have established institutions in which the marginalized have been conﬁ  ned, as recorded by Foucault.
(3) The distinction 
between immoral behaviour and mental illness was established in France at the end of the eighteenth century, coinciding with the birth of modern psychiatry. The Marquis de Sade was expelled from the Chârenton Hospital because, in words of the director, ‘he is not ill, his only madness is vice’ .
(3) Pinel (1745–1826) consid-
ered that, in the case of the young man who in an attack of rage threw a woman into a well, although his ability to judge was clear and intact and although he presented no delusional ideas, his behaviour was characteristic of a mental patient. Consequently, this murderer was diagnosed as suffering from manie sans délire

and his madness was classiﬁ  ed as reasoning madness  (folie raison-
nante ).
(4) This reasoning is similar to that of Cleckley 150 years 
later who proposed that the social maladaptation of psychopaths is of such high degree that should considered as the result of an underlying psychotic disturbance, being personality disorders are a mask of sanity.
(5)
Prichard,(6) deﬁ ned the concept of moral insanity from which, 
together with the moral degeneration described by Morel (1809–1873),
(7) the modern concepts of psychopathy and personality 
disorders are derived.
Difﬁ culties in the study of personality 
disorders
Two factors have prevented the development of scientiﬁ  c knowledge 
in this ﬁ  eld: ﬁ  rst the negative evaluation of the concept of moral 
insanity, and second the dualism inherent in psychopathology.
The stigma of personality disorder

The diagnosis of personality disorder generally implies the idea of intractability and frequently leads to a lack of proper medical care. This attitude is the expression of a negative, moralising, and, according to Tyrer et al.,
(8) delusional attitude of the doctor towards 
the patient. Cusack and Malaney(9) posed the question as to

the patient. Cusack and Malaney(9) posed the question as to 
whether patients with antisocial personality disorders are ‘bad’ or ‘mad’ . They attempted to establish differential criteria in order to show that if patients with an antisocial personality disorder are not ‘mad’ , then they must be considered as ‘bad’ and therefore must be delivered to the judicial system, after diagnosis and treatment of secondary symptoms. In 1999, the UK Government 1999 intro-duced a new concept: Dangerous and Severe Personality Disorder (DSPD). This subsequently became a treatment and assessment program for individuals who satisfy three requirements: 1) have a severe disorder of personality, 2) present a signiﬁ  cant risk of 
causing serious physical or psychological harm from which the victim would ﬁ  nd it difﬁ  cult or impossible to recover, and 3) the 
risk of offending should be functionally linked to the personality disorder.
(10, 11)

(10, 11)
Dualism in psychopathology
Dualism has been present in psychiatry since its origins as specialty. According to Griesinger:
(12)It is time that [mental medicine] should be cultivated as a branch of brain pathology and of [the study of] the nervous system in general, and to apply serious diagnostic methods used in all branches of medicine. . . . Besides this purely medical element, mental medicine has another essen-tial one and which gives a special and proper character to this part of the healing art; it is the psychological study of the aberrations of the intelligence observed in mental illnesses.
The radical separation between mental-brain illnesses and 
‘aberrations of intelligence’ is fundamental to modern psychopa-thology. Schneider
(13) distinguished between psychoses as patho-

logical conditions of the brain (disease or defective structure) and variations of the psychic way of being. Abnormal personalities, personality disorders, and neurotic disorders belong to the second category.
Schneider
(14) deﬁ nes some abnormal personalities  in a statisti-
cal sense, to describe those individuals whose form of feeling, experience and behaving differs to a certain degree from what is considered to be normal for most individuals in a social group. Some of these are psychopathic personalities  who, as a result of 
their abnormality, suffer or make others suffer. It should be stressed that according to Schneider’s statistical deﬁ  nition of personality

their abnormality, suffer or make others suffer. It should be stressed that according to Schneider’s statistical deﬁ  nition of personality 
and the dualism of his psychopathological system, the only possible criterion to deﬁ  ne a clinical condition in the absence of a brain dis-
ease is the suffering, the pathos. Suffering is for Schneider the rea-son why some people ask for medical care, but not a sufﬁ  cient cri-
terion for to determine the presence of an illness. Schneider had to add suffering inﬂ  icted on others (social suffering) in order to be 
able to include certain kinds of abnormal personalities characterized by the absence of personal suffering (heartless psychopaths, 
sociopaths).
It seems acceptable to consider as a patient someone who suffers

It seems acceptable to consider as a patient someone who suffers 
and asks for clinical care although the criterion for suffering is a weak one when compared with the presence of an illness of an organ. On the contrary, the criterion of induced suffering which characterises some psychopathic personalities, deﬁ  ned following 
Schneider, is not acceptable in medicine and it is surprising that this has been little criticised. The clue lies in Schneider’s deﬁ  nition 
of personality which excludes  any biological substrate.
(15) The effect 
of viewing psychopathies as simple variations was to reduce the amount of neurobiological research into the neuroses and person-ality disorders because they were not considered amenable to natural scientiﬁ  c methods. The study of the personality was left the 
new psychoanalytical and psychological theories.
Nowadays it is impossible to maintain such a reductionistic per-

spective, and it is recognised that the morbid nature of personality disorders can be understood through the study of changes in its biological substratum. There are not two kinds of mental disorders, the psychosis which are the consequences of brain illnesses, and the variations of the psychological way of being (neurosis and personality disorders), but two inherent aspects to each disorder. It is essential to consider psychological and psychopathological 
aspects of psychoses, as well as the brain dysfunction of the varia-
tions of the psychic way of being.
Models of personality
The study of personality by the different schools of differential psychology provides a solid background to help to understand the disorders of personality. Unfortunately, these studies have been

849
conducted from different and sometimes contradictory perspec-
tives, which are summarized in the following sections.
Categorical perspective
The categorical perspective is deep rooted in the psychiatric tradition. Categorical models consider discontinuous personality categories. This type of model is used in DSM-IV
(16) and ICD-10(17) because 
of the need for a speciﬁ  c diagnostic, i.e. a categorical approach.
In modern nosology the categorisation of illness is based on the 
symptoms present and not on their aetiopathology, and says nothing about the nature of the disorders themselves. In the case of personality disorders, the categorisation does not afﬁ  rm or deny 
that they are disorders or illnesses, nor does it indicate where the symptoms differ from non-morbid behaviour patterns.
This approach is supported by the notion of ideal types of Weber 
(1864- 1920), introduced into psychiatry by Jaspers (1883–1969) and more recently by Schwartz and Wiggins.
(18) Ideal types are

(18) Ideal types are 
constructs to understand reality: An ideal type is formed by a unilateral accentuation of one or more perspectives and by the synthesis of a great deal of individual phenomena. A type describes the perfect case. Recently Doerr
(19) has argued that the ideal types, 
when well described, become almost real types.
The experimental approach
The experimental approach looks for general laws on personality and establishes causal relations between personality variables. Wundt (1832–1920) studied the effects of modiﬁ  cations of stimuli on the

intensity and quality of the subject’s experiences introduced them. Pavlov (1849–1936) studied the conditioning of the res ponses to stimuli and the experimental neurosis. The behavioural approach to the personality was introduced by Watson (1878–1958) who applied objective methods to the study of human behaviour and to the relationship between stimuli and responses. Hull (1884–1952) expanded behaviourism to include learning, feelings, expectations, achievements, goals and motivations. This led to the notion that the stimulus response relationship is inﬂ  uenced by 
cognitive processes. Perception, memory, language and other func-tions inﬂ  uence the processing of information of the surrounding 
world and the information coming from oneself ( self) . Skinner

world and the information coming from oneself ( self) . Skinner 
(1904-1990) created a theory of the operating conditioning, result of a non-adaptative learning. From these perspectives, the person-ality is viewed as a computer which introduces, stores, transforms and produces information, including the contents of the informa-tion as well as the process in itself.
(20)
The psychoanalytical approach
Freud (1856-1939)(21) proposed in the course of his life three dif-
ferent models of personality: The ﬁ  rst was the speculative neuro-
psychological model of the Project of a psychology for neuropsychia-
trists  (1897) based on the concepts of psychic energy and 
psychodynamic. The second was the topographic model of the The
Interpretation of Dreams  (1900) where Freud described the con-

scious, preconscious and unconscious levels. The third is the struc-tural model of The Ego and the Id  (1923) and of Inhibition, 
Symptoms and Anxiety  (1926) where Freud introduced the notions 
of the Id, the Ego and the Super-Ego. This last model led to a new perspective, the psychology of the Ego and the description of defence mechanisms which have a strong impact on the study of personality in clinical settings. Defence mechanisms distort reality 
to adapt the subject to it and to reduce anxiety. Some of them are more normal (promote adaptation to the environment), others are pathological (maladjusted or maladaptative).
The correlational approach

The correlation approach explains the individual differences based on personality traits and applying a dimensional model based on statistical correlation. Karl Pearson (1857–1936), the founder of mathematical statistics introduced the correlation coefficient (correlates of cognitive ﬂ  air with variables like age, gender, weight, 
height and so on). Charles E. Spearman (1863–1945) applied to research on the traits of personality, a factorial analysis that groups different qualities around a series of correlational factors or dimensions.
Traits are the basic elements of a personality and individual 
differences are deﬁ  ned and classiﬁ  ed along dimensions. The theo-
retical assumption is that the structure of personality is common to all individuals; it differs in the different combination of traits. Trait is a disposition to respond in a determined way to a determined 
situation. Traits characterize persons through brief and precise

situation. Traits characterize persons through brief and precise 
descriptions on stable ways to behave, and as behaviour is consistent, it is possible to predict behaviours. This approach has paved the way to basic dimensions of individual differences.
Dimensional models
Jung (1875-1961) made the ﬁ  rst important contribution to the 
dimensional concept of the personality, based on the concept of trait or disposition.
(22) A trait is a permanent inclination towards 
behaving in a determinant way. Traits are distributed along dimensions which make it possible to classify individuals according to their personality. The different dimensional models are based on the supposition that we all share the same personality structure, differing in the different combination of the mentioned traits. These models have beneﬁ  ted from the innovative statistic tech-
niques, which allows to group different qualities of the individual character around factors of correlation or dimensions.

This dimensional approach raises several questions. How many 
traits deﬁ  ne personality? Are the traits universal? Do traits relate 
only to manifest behaviours or are they part of feelings, values or thoughts? The problem of the number of dimensions that deﬁ  ne 
personality led to the search for external validators such as biologi-cal, cultural and genetic factors. Eysenck
(23) identiﬁ  ed there are 
three basic types of personality: extroversion-introversion, neuroti-cism and psychoticism, each one including multiple levels of traits. For Eysenck and Eysenck,
(24) the concept of arousal level is essen-
tial. Every individual has an optimal activation level of speciﬁ  c sys-
tems of the central nervous system—the better they feel, the better they will perform. This approach has been developed by many authors including Zuckermann,
(25) who described sensation-

seeking behaviour, Oreland et al.,(26) and Siever and Davis,(27) who 
proposed new traits and dimensions.
Cloninger(28) initially proposed three dimensions: novelty-seek-
ing, harm avoidance, and reward dependence. Latter, he attempted to overcome the dichotomy between dimensional and categorical models by using four temperamental dimensions (novelty-seeking, harm avoidance, reward dependence, and persistence), which are life-long and stable, and three character dimensions (self-direction, 4.12.1 personality disorders: an introductory perspective

SECTION 4  clinical syndromes of adult psychiatry 850
co-operation, and self-transcendency) which are variable and sus-
ceptible to environmental inﬂ  uences and development.(29)
The ﬁ  ve-factor model, based on factorial studies and individual 
differences(30) has been widely accepted. It comprises the personal-
ity dimensions openness, conscientiousness, extraversion, agree-ableness, and neuroticism, known by the acronym OCEAN. About 40 per cent of individual personality differences can be explained in terms of heredity.
(31) In the ﬁ  ve-factor model the same propor-
tion does not apply to each factor; openness to experience appears to have the greatest hereditary input, whereas conscientiousness appears to have the least.
Mathematical tools allow recombining the data in order to ﬁ  nd

Mathematical tools allow recombining the data in order to ﬁ  nd 
higher order factors of the Big Five. Two of them have appeared in many studies: 1) related to the Big Five trait dimensions Agreeableness, Conscientiousness, and Emotional Stability (meta-trait alpha) and 2) the dimensions Extraversion and Intellect (meta-trait beta).
(32) Other have found some extra traits to be 
added to the Big Five, such as honesty-humility.(33)
An interesting approach is lexicographic, which is based on the 
examination of relations among personality-descriptive adjectives that are indigenous to various languages. They tend to reveal a structure corresponding closely to the Five-Factor Model, with some differences in the nature of the Agreeableness and Emotionality/Neuroticism factors and also in the existence of a sixth factor, Honesty-Humility.
(34) This has been found in different

(34) This has been found in different 
languages such a tagalong with some differences (a Filipino extra factor resembled a Negative Valence or Infrequency dimension).
(34)
A study with college students yielded seven major dimensions; many of the factors were similar to recognized lexical personality factors. Big Five Conscientiousness and Neuroticism were each strongly associated with a single proverb dimension (interpreted as Restraint and Enjoys Life, respectively). Big Five Agreeableness, Extraversion, and Intellect/Imagination were all associated with several proverb dimensions. Agreeableness was most strongly associated with proverb dimensions representing Machiavellian behaviour and strong Group Ties, and both Extraversion and Intellect showed particularly notable associations with an Achievement Striving dimension. The two remaining proverb dimensions, which represented a belief that Life is Fair and an atti-tude of Cynicism, could not be accounted for by the Big Five.
(35)

(35)
Critics of this approach have argued that a) little progress has 
been made in this area, b) structural models have little direct rele-vance for psychopathology research, c) the principal methodologi-cal tool of structural research–factor analysis–is too subjective to  yield psychologically meaningful results and 4), some clinically rel-evant aspects, such as alexithymia or impulsivity, do not appear in the studies on the structure of personality.
Alexithymia positively correlates with Neuroticism (N) and 
negatively with Extraversion (E) and Openness (O), whereas no significant relations were found with Agreeableness (A) and Conscientiousness (C).
(36) Impulsivity. The term impulsive mad-
ness was used in German literature and Jaspers(37) put it in relation 
to nostalgia and displacement. The balance between social and individual norms is related to the origin of mental disorders. Durkheim
(38) introduced the concept of anomia  when describing

(38) introduced the concept of anomia  when describing 
a particular form of suicide in individuals who perceive that their own norms and values are no longer relevant and that their relation to the community is weak or non-existent. However, the opposite may also occur. Kraus
(39) coined the term hypernomiafor premorbid personality traits of depressive patients, which 
consist in an exaggerated form of adaptation to social norms. This personality type is the converse of the impulsive madness that can be characterized as hyponomic . We have proposed the term dys-
nomic  for obsessive patients
(40) who show a distorted adaptation

(40) who show a distorted adaptation 
to social norms. For example, patients with obsessions and com-pulsions related to cleanliness usually appear to be extremely dirty because of their fear of contamination and their unrealistic com-pulsions, which are based more on ‘magic’ control than on efﬁ  cient 
behaviour oriented towards concrete goals.
The common link in the psychopathology of obsessive-compul-
sive disorders and the group of impulsive disorders experienced by the impulsivists
(41) is poor control of the impulses, in the sense 
that novel interior or exterior experiences are not converted into adequate behavioural patterns. Rather, obsessives abandon actions uncompleted and impulsivists behave in a disorganised manner (acting out). In both cases, ‘the irrelevant substitutes the relevant’ .
(42)
T oday, the trend is to look for a classiﬁ  cation of personality

(42)
T oday, the trend is to look for a classiﬁ  cation of personality 
disorder which will be dimensional, either by selecting one of the existing models by developing a common, integrative represen-tation including the important contributions of each of the models.
(43)
Models of personality and personality 
disorders
The ideal goal of a single structural framework to be applied to 
normal and abnormal personality is not easy to reach. In a study with the Eysenck Personality Questionnaire-Revised (EPQ-R) the three clusters of personality disorders of DSM found equivocal support. Exploratory principal components analysis and conﬁ  rma-

tory factor analysis found four broad factors of personality disor-der that overlapped with normal personality traits: an asthenic factor related to neuroticism; an antisocial factor associated with psychoticism; an asocial factor linked to introversion-extraversion; and an anankastic (obsessive-compulsive) factor. In spite of this, there is growing agreement about the number and type of broad personality disorder dimensions; similar dimensions may be found in clinical and non-clinical samples, suggesting that those people with personality disorders differ quantitatively rather than qualita-
tively from others; and there is substantial overlap between normal 
and abnormal personality dimensions.
(44) For Livesley et al .,(45) 
personality disorders are quantitatively extreme expressions of

personality disorders are quantitatively extreme expressions of 
normal personality functioning developed around four factors: Emotional Dysregulation, Dissocial Behaviour, Inhibitednessand Compulsivity. In the same year, the same group published some different results in another study:
( ) they found 16 basic
dispositional traits (anxiousness, affective lability, callousness,cognitive dysregulation, compulsivity, conduct problems, insecure attachment, intimacy avoidance, narcissism, oppositionality,rejection, restricted expression, social avoidance, stimulus seeking,submissiveness, and suspiciousness) and three higher-orderpatterns (emotional dysregulation, dissocial behaviour, andinhibitedness).
(46)
Markon et al .(47) have delineated an integrative hierarchical 
account of the structure of normal and abnormal personality. This hierarchical structure integrates many Big Trait models proposed

851
in the literature. Similarly, O’Connor(48) reanalyzing the published 
studies found high level of support for both theoretically and empirically based representations of the ﬁ  ve-factor model approach 
to personality disorders. The ﬁ  ve-factor model personality dimen-
sions of Neuroticism, Extraversion, and Agreeableness are the most apparent in the DSM-III-R conceptualizations of the personality disorders.
(49,50) The ﬁ  ve-factor model structure is present although 
with some variance in the current DSM-IV cluster set.(50)
Mulder and Joyce(51) have attempted to construct a simpliﬁ  ed 
system for the classiﬁ  cation of personality disorders related to nor-

mally distribute human personality characteristics. A four-factor solution of personality disorder symptoms was obtained and they labelled these factors ‘the four As’: Antisocial, Asocial, Asthenic and Anankastic. The factors related to the four temperament dimen-sions of the Tridimensional Personality Questionnaire (TPQ), but less closely to Eysenck Personality Questionnaire (EPQ) dimensions. The four factors were similar to those identiﬁ  ed in a number of 
studies using a variety of assessment methods and this lends some credibility to our ﬁ  ndings.
The masking of sanity becomes evident in some dissocial, 
psychopathic and even criminal behaviours that are the expression of underlying disorders. The issue is very relevant because those

psychopathic and even criminal behaviours that are the expression of underlying disorders. The issue is very relevant because those 
can be treated. One example is attention deﬁ  cit hyperactivity disor-
der (ADHD) which has important forensic implications. For decades there has been an interest in predicting which children will become psychopaths in order to establish primary prevention interventions. Lynam
(52) described the fledgling psychopath, 
characterized by symptoms of hyperactivity-impulsivity-attention problems and conduct problems are at the greatest risk for becom-ing chronic offenders. Other authors
(53,54) have strongly argued 
against the clinical-forensic utility of tests designed to assess juvenile psychopathy.
The problems of axis II of the diagnostic and 
statistical manual
There are several reasons in favour of an independent axis for

There are several reasons in favour of an independent axis for 
personality disorders. First it is important not to forget personality in the diagnostic process, especially when using symptomatic classiﬁ  cations (DSM-III / IV and ICD-10). Second, personality may 
be a predisposing factor, or something essential for the response to treatment and for prognosis.
(54) Third personality traits are 
egosyntonic: they include traits that the subject has accepted as an integrative part of him/herself in a progressive way (when com-pared to axis I disorders and non-psychiatric illnesses which are something ‘that occurs’).
Seen from a theoretical perspective, personality disorders may be 
considered as the expression of the personality’s functioning, which is essential for patients, be they psychiatric or not.
(45)
But there are also reasons to combine Axis I and Axis II. The

(45)
But there are also reasons to combine Axis I and Axis II. The 
better a personality disorder is known and the more biological correlations are found in it, the higher the probabilities it has to be moved to Axis I: Epileptic personality (adhesivity, gliscroidy) became long ago organic disorder of the personality, cyclothymic personality became cyclothymia and depressive personality (at least in part), dysthymia in DSM-III. Schizotypal personality is schizo-typal disorder in ICD-10 and several studies emphasise the strong relation of borderline personality disorder and mood (affective) disorders.
(55)Although through most of the 20th century, from K. Schneider 
to DSM-IV , personality disorders and mental illnesses were studied as separate ﬁ  elds, there has been increasing recognition of the

to DSM-IV , personality disorders and mental illnesses were studied as separate ﬁ  elds, there has been increasing recognition of the 
substantial overlap of – and comorbidity between – disorders both within and across axes and interest in the joint study of normal and abnormal personality.
(56) In comorbid cases, the personality 
disorder could be a predisposing factor, a consequence, or an atten-uated form of the mental disorder, or it could be independent of the mental disorder. The fact that the association between a mental disorder and a personality disorder is not always fortuitous has been shown by the observation that effective treatment of the for-mer can lead to the disappearance of the latter, as has been demonstrated in the treatment of obsessive-compulsive patients with pharmacotherapy and behavioural therapy.
(57)
The main difference between mental and personality disorders

(57)
The main difference between mental and personality disorders 
may be that the latter are early onset variants with a very chronic course. According to the hypothesis of a spectrum of disorders, per-sonality disorders can often be treated by the same method as those applied to the major psychiatric disorders to which they are related. Patients with anxious or avoidant personality disorder may respond to anxiolytic medication, patients with borderline personality disor-der may respond to lithium and antidepressives, patients with schizo-typal personality disorder may respond to antipsychotic agents, and patients with disorders characterised by poor impulse control may respond to antidepressives with a selective serotonergic action.
The diathesis-stress model

The diathesis-stress model has been used to explain the relation-ship between personality and mental disorders. Supposedly broad, innate temperament dimensions, sometimes correlated with somatic characteristics such as body type (Kretschmer [1888–1964]), develop and differentiate themselves through both biologically and environmental events into a hierarchical personality trait structure. At their extremes, are risk factors (diatheses) for psychopathology, especially given adverse life experiences (stress). Rosenthal
(58)
deﬁ ned this model as an inherent constitutional predisposition 
which only becomes apparent under the impact of environmental stress.
The onset early in life, the variability of expression dependent 
on setting, the greater association with more severe disorders and 
the acceptance as intrinsic components of functioning by most suffering from personality disorders support the notion that they are diatheses rather than disorders.
(59)

(59)
Personality disorders have been considered as belonging to the 
spectrum of major psychiatric disorders. However, it must be remembered that external events, such as brain damage (organic personality disorders), or the psychological impact of a catastrophic event may also lead to personality changes. Severe psychiatric dis-orders may have a repercussion on the personality of the patient, and other illnesses may also have this effect. For example, chronic pain (of organic nature) can be accompanied by a profound per-sonality change (algogenic psychosyndrome). Hypochondria or dissociative symptoms and traits may become relevant only after the patient has suffered an illness, or a problem related to diagnosis or treatment, or a problem involving the patient–physician relationship.

Recent research has focused on the impact of social conditions 
in the neuroendocrine regulation of the individual, especially 4.12.1 personality disorders: an introductory perspective

SECTION 4  clinical syndromes of adult psychiatry 852
regarding the adaptation to stressful situations. In patients with 
borderline personality disorder and suicidal impulsive behaviour we have found when compared to the control group, high basal concentrations of cortisol (suggesting a high level of stress) and a very blunted response to the stimulus (suggesting a reduced capacity to respond to external stimulus).
(60) A clue to the interpre-
tation of these results lies in the work of Sapolsky,(61) who has stud-

ied the adaptation to stress of baboons in the Serengeti savannah in Africa. Males of a lower rank have consistently high concentrations of the stress hormone hydrocortisone in their blood, whereas the concentration is lower in the dominant males. However, in the dominant males hydrocortisone concentrations increase rapidly at times of stress and decrease once the situation is resolved, whereas the lower-order males, who live in a permanent state of stress, are unable to initiate more adaptive resources (increase hydrocortisone secretion) when new stressful events appear. These patterns are the consequence and not the cause of the rank (if the opposite were true, the baboons who were physiologically better able to respond to stressful situations would achieve a higher rank). During periods of revolution, members of the colony hold successively different

ranks and, although there is always one dominant animal, the 
stability of the society is lost and with it the stress-adapted physiol-ogy of the dominant males who show prolonged increased hydro-cortisone concentrations like the rest of the group. When calm is established again, the normal pattern related to the hierarchical rank of the baboons is restored regardless of what their cortisol secretion pattern was prior to the revolution.
Relational disorders
This model can be applied to the relational disorders or processes. On one side every clinician has the experience of persons whose behavioural problems happen in speciﬁ  c environments (i.e., the 
family) or in relation to speciﬁ  c persons (i.e., the spouse) while their

family) or in relation to speciﬁ  c persons (i.e., the spouse) while their 
behaviour is totally normal in the rest of circumstances. Another observation is the case of personality disorders that once beginning to improve after a therapeutic intervention, the whole atmosphere around him or her changes. The patient himself and their relations start to consider that the personality as not a stable and incorrigible set of traits but something that can change for the better. However, it is the inﬂ  uence of child psychiatrists looking for child-
hood antecedents of mayor psychiatric disorders of adulthood
(62)
and family therapists that have requested a new diagnostic category to describe these situations.
It has also been claimed that in order to be able to proceed along

(62)
It has also been claimed that in order to be able to proceed along 
this line, some problems have to be addressed, although the same may also be present in diagnostic categories accepted in DSM-IV and ICD-10. The main one are: 1) the little consensus on assess-ment means; 2) the complexity of relational assessment, which results in a lack of well-accepted, evidence-based operational deﬁ  -
nitions; 3) insufﬁ  cient empirical testing of relational issues; and 4) 
the resistance to labeling social difﬁ  culties as disorders.
(63)
These difﬁ  culties can be surmounted if new diagnostic perspec-

(63)
tives are implemented. One is the concept of diseases as harmful dysfunctions a view which holds that disorders are harmful failures of biologically selected functions. There are evolutionarily selected functions that depend for their performance on the nature of the interaction between individuals. These relations can fail, even when both individuals are normal, because of mismatches betweennormal variations. Thus, there are genuine relational dysfunctions 
that, when harmful, are relational disorders.
(64)The Structural 
Analysis of Social Behavior (SASB) has operationalised interper-sonal theory for the research of relational aspects of psychopathol-ogy and becoming a useful diagnostic tool.
(65)
The research agenda for DSM-V recognizes that the diagnosis 
of relational disorders is one of the most important gaps in the current DSM-IV .

(65)
(66) Speciﬁ  c recommendations include developing 
assessment modules, determining the clinical utility of relational disorders, determining the role of relational disorders in the aetiol-ogy and maintenance of individual mental disorders, and consider-ing aspects of relational disorders that might be modulated byindividual mental disorders.
Personality disorders vs. personality variants
It is necessary to establish a clear distinction between personality disorders and personality variants, and to view the former as true morbid entities. ICD-10 allows us to differentiate, at least theoreti-cally, personality disorders that appear in the chapter on mental disorders from personalities relevant for medicine in Chapter Z.
(67)

(67)
Personality disorders should be characterised by the presence of symptoms, and relevant personalities by their traits. Symptoms are used as diagnostic criteria in a categorical classiﬁ  cation, while 
psychological traits can be classiﬁ  ed according to dimensions.
Personality variants relevant to medicine, although not morbid, 
play an important role in the aetiopathogenesis of illnesses or are important for prognosis and rehabilitat ion. The study of the variants 
of personality also reminds the practitioner of the necessity to identify the uniqueness of the patient’s personality.
The frontiers with normal personality are not well explained 
or justiﬁ  able threshold,
(68) except for schizotypal disorder and 
borderline disorder. There are great variations between the different versions of DSM (DSM-III - DSM-III-R) leading in the case of schizotypal disorder to a reduction of prevalence from 11 per cent to 1 per cent.
(69)

(69)
On the other hand, normal the population also presents malad-
aptative variants of traits such as: neuroticism, irritability, vulner-ability, anxiety, depression, impulsivity, low consciousness, rush, 
negligence, hedonism, immorality, unreliable, irresponsibility, high antagonism, manipulation, disappointment, exploitation, aggressiveness, cruelty, heartless.
In everyday practice there is a need for categorical approach, 
essential to deﬁ  ne the frontiers of clinical activity, for research, for 
management and for forensic questions and also of a dimensional approach, to identify functions and its alterations, relevant for inter-ventions with patients. This could be done investigating in new personality models, adopting the multi-axial version of ICD-10
(70)
(Table 4.12.1.1.), implementing diagnostic system that include a nosographic approach and idiographic perspective
(71) or adopting 
Table 4.12.1.1  Multiaxial formulation of ICD-10

(70)
Axis I Clinical disorders (DSM-IV axis I, II and III): personality disorders 
understood as morbid states of the personality
Axis II DisablementAxis III Relevant non morbid circumstances, including variants of the 
personality (i.e., Type A behaviour)
Normal personality traits (i.e.: ﬁ  ve factors model)

853
a new multiaxial system(72) (Table 4.12.1.2). Several authors 
have claimed for a functional psychopathology. Van Praag(73) has 
recommended a two-tier diagnosis: 1) nosological diagnosis and 2) psychological dysfunctions correlated with biological variables.
The cosmetic of the personality?
Cosmetic or palliative pharmacotherapy is to use a psychotropic agent to make feel better to a person who is not ill. It usually intents to mitigate unwanted or unaccepted personality traits in order to attain a higher order of social normality and acceptability. Kamer
(74)

(74)
has described how a selective serotonin uptake inhibitor used for the treatment of depression and for other psychiatric alterations can remove personality traits in some people. He has considered traits previously considered as an expression of human misery or, in some cases, as the consequence of negative childhood experiences. Kamer even questions whether there could be a ‘pandemic’ of cosmetic psychopharmacologies which would lead to the dis-appearance of phenomena such as anguish which are essential for personal realisation in the arts, religion, and creativity. For example, ﬂ uoxetine can make non depressed people feel more vital, mentally 
more alert and become more popular, leading to an increased feel-ing of wellness. Shyness became a treatable illness when paroxetine was found to improve the symptoms of social phobia and atomox-
etine can change the life conditions of adults with a history of

etine can change the life conditions of adults with a history of 
ADHD. Most of these cases are probable subthreshold clinical conditions, something which may lead to a change in diagnostic habits, lowering thresholds or modifying criteria. For instance the DSM criteria of suffering or disablement are value loaded, and new values, such as wellbeing may be introduced.
During the last few decades there has been an impressive growth in research and knowledge on personality disorders. There is a strong growing evidence that they are “real” disorders that can be man-aged in ways similar to the rest of psychiatric disorders. There is also a growing consensus on the need for a new classiﬁ  cation able 
to capture the nuances beyond the rigidity of present nosological systems. There is also a need for a clearer delimitation from normal personality variants something that will have important impacts, 
for instance in forensic settings or for reimbursement purposes.

International Society for the Study of Personality Disorders (ISSPD)
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4.12.2  Diagnosis and classiﬁ  cation 
of personality disorders

Deﬁ nitions of personality disorders
There has been considerable interest in the study of personality and 
personality disorder (PD) since early times and in many different cultures. However, as noted by Tyrer et al.
(1) ‘The categorization of 
personality disorder did not receive any ﬁ  rm support until the 
time of Schneider’ . Schneider(2) regarded abnormal personalities 
as ‘constitutional variants that are highly inﬂ  uenced by personal 
experiences’ and identiﬁ  ed 10 speciﬁ  c types or classes of ‘psycho-
pathic personality’ . The classiﬁ  cation system proposed by Schneider 
has deeply inﬂ  uenced subsequent classiﬁ  cation systems(1): of the 
10 types of PD identiﬁ  ed by Schneider, eight are closely related to 
similar types of PD as classiﬁ  ed in DSM-III.(3) Many of these cate-

gories are also represented in DSM-IV(4) and ICD-10.(5)
Personality is deﬁ  ned in the second edition of the WHO Lexicon 
of Psychiatric and Mental Health Terms(6) as ‘The ingrained patterns 
of thought, feeling, and behaviour characterising an individual’s unique lifestyle and mode of adaptation, and resulting from consti-tutional factors, development, and social experience’ . Personality disorders, according to the ICD-10 diagnostic guidelines
(5):
 . . . comprise deeply ingrained and enduring behaviour patterns, manifesting themselves as inﬂ  exible responses to a broad range of per-
sonal and social situations. They represent either extreme or signiﬁ  cant deviations from the way the average individual in a given

sonal and social situations. They represent either extreme or signiﬁ  cant deviations from the way the average individual in a given 
culture perceives, thinks, feels, and particularly, relates to others. Such behaviour patterns tend to be stable and to encompass multiple domains of behaviour and psychological functioning. They are fre-quently, but not always, associated with various degrees of subjective distress and problems in social functioning and performance.
For example, a dependent PD in a favourable environment might 
not cause dysfunction, but nevertheless might be considered a dis-order since it is clinically identical to the same disorder that usually causes dysfunction.
DSM-IV
(4) deﬁ nes a PD as ‘an enduring pattern of inner experi-
ence and behaviour that deviates markedly from the expectations of the individual’s culture’ . The pattern is manifested in two or

DSM-IV
ence and behaviour that deviates markedly from the expectations of the individual’s culture’ . The pattern is manifested in two or 
more of the following areas: cognition, affectivity, interpersonal functioning, and impulse control. The pattern is inﬂ  exible and 
pervasive across a broad range of situations, has an early onset, is stable and leads to signiﬁ  cant distress or impairment.
Personality traits, according to DSM-IV ,
(4) ‘are enduring patterns 
of perceiving, relating to and thinking about the environment and oneself that are exhibited in a wide range of social and personal contexts. Only when personality traits are inﬂ  exible and maladap-
tive and cause signiﬁ  cant functional impairment or subjective 
distress do they constitute PDs.’
ICD and DSM classiﬁ  cations of personality 
disorders
Table 4.12.2.1 lists the specific PDs as classified in ICD-9,(7)
ICD-10, DSM-IIIR,(8) and DSM-IV .

disorders
In the ICD-10 classiﬁ  cation, which does not have a multiaxial 
system for the separate recording of the personality status, PD can be diagnosed together with any other mental disorder, if present. Although a multiaxial system for ICD-10 is being developed, this will not include a separate axis for PDs, as in DSM-IV .
Despite the importance given to behavioural manifestations for 
the classiﬁ  cation and assessment of PDs, personality traits and atti-
tudes are also considered when a diagnosis is made. The ICD-10 
diagnostic guidelines subdivide PDs ‘according to clusters of traits 
that correspond to the most frequent or conspicuous behavioural 
manifestations’ . As stressed by Widiger and Frances,
(9) the reliance

(9) the reliance 
on behavioural indicators can improve inter-rater reliability, which reduces the amount of inferential judgement required for the diag-nosis, but it does not ensure that the same diagnosis will be made at different times. Moreover, the diagnosis of a PD cannot be based on a single behaviour, as any given behaviour may have multiple causes (e.g. situational and role factors).
There have been four studies that have explored the diagnostic 
categories for PDs contained in ICD-10 and compared them with the DSM classiﬁ  cation. The ﬁ  rst
(10) was carried out among

(10) was carried out among 
177 American clinicians who found some degree of overlap between the different categories. When the authors compared the diagnostic categories in ICD-10 with those in DSM-IIIR, they found that only anankastic (ICD) and obsessive–compulsive (DSM) PDs showed a high level of correspondence. The second study
(11) looked at 
52 outpatients and compared DSM-IIIR to ICD-10. It found fair concordance for the diagnosis of ‘any PD’ , but poor agreement for individual PDs; the ICD-10 tended to overdiagnose PDs relative to DSM-IIIR. The third report
(12) compared ICD-10 and DSM-IV in 
58 patients with panic disorder. There was good agreement for the presence of ‘any PD’ , and a reasonable agreement between individual diagnoses ( κ ranged from 0.51 to 0.83.), with a tendency

58 patients with panic disorder. There was good agreement for the presence of ‘any PD’ , and a reasonable agreement between individual diagnoses ( κ ranged from 0.51 to 0.83.), with a tendency 
for ICD-10 to overdiagnose PDs relative to DSM-IV . In the fourth study,
(13) ICD-10 criteria were found to have satisfactory inter-
rater reliability in a sample of homeless adults.
In the American taxonomic system, a multiaxial classiﬁ  cation 
was ﬁ  rst introduced in DSM-III. With the development of DSM-
IIIR, more than 100 changes in the classiﬁ  cation of PDs were intro-
duced compared with DSM-III.(14,15) While the multiaxial and 
categorical style of classiﬁ  cation was maintained, the diagnostic 
criteria were revised to form a list of symptoms for each PD, of 4.12.2 diagnosis and classification of personality disorders

SECTION 4  clinical syndromes of adult psychiatry 856
which only a certain number were required for a diagnosis to be 
reached. In DSM-IIIR, each category of PD comprised 7 to 10 criteria, with the presence of four to six criteria required for diagnosis. DSM-IIIR contained 11 PDs (see Table 4.12.2.1), plus two new dis-orders (self-defeating PD and sadistic PD) that were not included in DSM-III but were considered as diagnostic categories needing further study. As in DSM-III, the 11 PDs were divided into three clusters:
X cluster A (the ‘odd’ or ‘eccentric’ cluster), which included 
paranoid, schizoid, and schizotypal PD;
X cluster B (the ‘dramatic’ or ‘erratic’ cluster), which included 
histrionic, narcissistic, antisocial, and borderline PDs; and
X cluster C (the ‘anxious’ cluster), which included avoidant, 
dependent, obsessive–compulsive, and passive–aggressive PDs.
One study in the United States examined changes in personality

One study in the United States examined changes in personality 
diagnoses using DSM-III versus DSM-IIIR.(16) For some categories 
there was a considerable difference in the frequency of diagnosis: for example, there was an 800 per cent increase in the rate of schizoid PD and a 350 per cent increase in the rate of narcissistic PD diagnosed by the clinicians when DSM-IIIR criteria were applied.
DSM-IV was designed to be a conservative evolution from 
DSM-IIIR; however, some differences in diagnoses between DSM-IIIR and DSM-IV can be expected.
(17) In general, the different 
DSMs should not be considered interchangeable unless there is speciﬁ  c data supporting agreement of a diagnosis across systems. 
As shown in Table 4.12.2.1, DSM-IV includes 11 PDs as in the DSM-IIIR classiﬁ  cation; slight changes were introduced in the

As shown in Table 4.12.2.1, DSM-IV includes 11 PDs as in the DSM-IIIR classiﬁ  cation; slight changes were introduced in the 
diagnostic criteria, and a new category ‘PD not otherwise speciﬁ  ed’ added. Passive–aggressive, self-defeating, and sadistic PDs (provi-
sionally included in DSM-IIIR) were dropped. The overall effect of these changes will be to increase the concordance between the DSM-IV and the ICD-10 classiﬁ  cation systems compared with that 
between DSM-IIIR and ICD-10. DSM-IV also includes the three clusters present in DSM-IIIR.
Similarities differences between ICD-10 
and DSM-IV
Table 4.12.2.1 shows that for seven categories of PD (paranoid, 
schizoid, dissocial/antisocial, histrionic, anankastic/obsessive–compulsive, anxious/avoidant, and dependent), there is a speciﬁ  c

schizoid, dissocial/antisocial, histrionic, anankastic/obsessive–compulsive, anxious/avoidant, and dependent), there is a speciﬁ  c 
correspondence between ICD-10 and DSM-IV . For three catego-ries, there are differences in nomenclature between the two systems; in particular ICD-10 uses the term ‘anankastic’ instead of ‘obsessive–compulsive’ , to avoid the erroneous implication of an inevitable link between this type of personality and obsessive–compulsive disorder. ICD-10 also uses the term ‘dissocial’ instead of ‘antisocial’ , to prevent any possible connotation of stigmatization, and the term ‘anxious’ instead of ‘avoidant’ . Moreover, while DSM-IV classiﬁ  es borderline PD as a speciﬁ  c category, ICD-10 includes 
it as a subcategory of emotionally unstable PD. Narcissistic and passive–aggressive PDs (present in DSM-IV) are included in ICD-10 
under the category of ‘other speciﬁ  c PDs’ . Finally, while DSM-IV

under the category of ‘other speciﬁ  c PDs’ . Finally, while DSM-IV 
includes schizotypal PD as a PD, ICD-10 classiﬁ  es it in the overall 
group of ‘Schizophrenia, schizotypal and delusional disorders’ , to highlight the contiguity between this disorder and the schizo-phrenia group disorders, as shown by genetic and clinical studies. DSM-IV has the category ‘Personality disorders not otherwise Table  4.12.2.1  Comparison of different classiﬁ  cation systems of personality disorders: ICD-9, ICD-10, DSM-IIIR, and DSM-IV
ICD-9 ICD-10 DSM-III-R DSM-IV
Paranoid personality disorder Paranoid personality disorder Paranoid personality disorder Paranoid personality disorder
Schizoid personality disorder Schizoid personality disorder Schizoid personality disorder Schizoid personality disorderPersonality disorder with 
 predominantly sociopathic or 
 asocial manifestationsDissocial personality disorder Antisocial personality disorder Antisocial personality disorder

predominantly sociopathic or 
Explosive personality disorder
NAEmotionally unstable personality 
 disorder:
Impulsive type
Borderline typeNA
Borderline personality disorderNA
Borderline personality disorder
Histrionic personality disorder Histrionic personality disorder Histrionic personality disorder Histrionic personality disorderAnankastic personality disorder Anankastic personality disorder Obsessive-compulsive personality disorder Obsessive-compulsive per sonality disorder
NA Anxious [avoidant] personality 
 disorderAvoidant personality disorder Avoidant personality disorder
NA Dependent personality disorder Dependent personality disorder Dependent personality disorder
Affective personality disorder
Asthenic personality disorderOther speciﬁ  c personality 
 disordersPassive-aggressive personality disorder

Narcissistic personality disorder
Self-defeating personality disorder
Sadistic personality disorderNA
NA
NA
Personality disorder not otherwise speciﬁ  ed

857
speciﬁ  ed’ , while ICD-10 has the category ‘Other speciﬁ  c personality 
disorders’ .
Changes in the conceptualization of DSM 
personality disorders since the last edition of this chapter
Empirical research has advanced in the years following the original 
chapter in an earlier volume. These changes have impacted our understanding and use of DSM measurement instruments. These changes are that the personality disorders as described by DSM are not as enduring as we once thought. The instruments to measure the DSM PDs have modest agreement at best on the categorical level. Finally these instruments do not seem to adequately ﬁ  t most 
of the disorders diagnosed which are diagnosed in the remainder category, ‘Personality Disorder NOS’ .
1.  Research indicating lack of enduring quality of personality 
There has now been considerable research indicating that some 
aspects of personality are state like. This was a line of research pur-sued by Reich

(18,19) and later conﬁ  rmed by others.(20) This means 
that some personality traits may disappear relatively rapidly—the state component. Experienced researchers have also found that even when personality disorders are selected for long-term study by careful methods, signiﬁ  cant percentages of these will not be 
found on retest within a 6 month to several year periods.
(21,22)
2.  Modest agreement of personality DSM personality disorder 
instruments.
Research has been fairly consistent from the beginning of DSM 
instruments that while they may measure aspects of clinical relevance even well-designed instruments of the same design (self-report or semi-structured interview) are compared on categorical diagnoses, the agreements are usually modest at best.
(23) (The

(23) (The 
results improve somewhat when using dimensional measures.) In addition when personality disorders are measured in a clinical population very few ﬁ  t into the established categories and most 
wind up in the ‘remainder bin’ of personality disorder NOS.
(24)
3. The problem of chasing changing criteria.Each time the wording of a questionnaire is changed it can make 
signiﬁ  cant difference in the outcome of the questionnaire or survey 
even though the changes may seem minor. This means that for every change in a version of the DSM, the DSM personality test developers would theoretically have to do extensive reliability and validity testing all over again. Unfortunately this is a time-consum ing

and expensive process which is beyond the resources of most DSM test developers. What happens instead is that either they do not update their instrument or update only the questions to conform to the new DSM criteria without doing new validity testing. Although these updated tests may have ‘face validity’ they (under-standably) do not have extensive reliability and validity testing.
4. Conclusions from intervening research on DSM personality 
At the end of the day we are left with the DSM personality meas-
urement instruments being limited by the conceptualizations behind them which may be incorrect. These errors may either by in the enduring nature of the personality disorders and the nature of the proper categories or the nature of the speciﬁ  c criteria for a 
category. These measures then become good dimensional measures of various aspects of personality pathology and a rough clinical

category. These measures then become good dimensional measures of various aspects of personality pathology and a rough clinical 
guide for ‘disorder’ . However, no one should expect that what one of these instruments is measuring is really the same as another. They do, however, conform to the DSM nomenclature.
Categorical versus dimensional styles 
of classiﬁ  cation
In general, researchers involved in the assessment of personality 
traits tend to use dimensional measures based on normal popula-tions. In contrast, those concerned with personality types and, even more, clinicians concerned with PDs, tend to employ cate-gorical concepts and assessment measures based on these concepts.
(15)
Each of the two approaches has specific advantages and 
disadvantages. The drawbacks of the categorical approach are represented by the difﬁ  culty of classifying patients who are at the

(15)
disadvantages. The drawbacks of the categorical approach are represented by the difﬁ  culty of classifying patients who are at the 
boundary of different categories or who do not meet the diagnostic criteria for any speciﬁ  c PD, but who still have signiﬁ  cant pathology. 
Other points that should be addressed include the wide variation of symptomatology found within each given category, the need for heterogeneous categories, such as ‘mixed’ and ‘atypical’ , the need to simplify necessarily complex conditions, the need to deﬁ  ne 
valid cut-off points, and the use of a nominal rather than an ordinal scale.
Those in favour of a dimensional approach argue that PDs differ 
from normal variations in personality only in terms of degree, and to some extent this is supported by empirical data.
(25,26) However,

(25,26) However, 
there is evidence that some dimensional models do not account for all of the abnormal personality traits (see discussion on the ‘Big ﬁ  ve’ models below.)
Moreover, it is still unclear whether normal and abnormal 
personality traits are the same or whether they are qualitatively different. Two main ﬁ  ndings seem to support the latter hypothesis: 
ﬁ rst, normal personality traits are at least moderately heritable, 
while abnormal personality traits appear less heritable; second, the prevalence rates of PDs found in surveys are much greater than would be expected from the prevalence rates of normal personality traits in the general population. Some researchers
(27) have even

(27) have even 
suggested that an extreme form of a normal personality trait is not necessarily pathological. Although some authors argue that there is no difference between normal and abnormal personality traits,
(25)
and this is still an area of open inquiry, it does appear more and more likely that there are some abnormal personality traits that dif-fer from normal ones. It is possible that different models may be appropriate in different situations.
1.  ‘Big Five’ personality measures and DSM-IV personality 
disorders
Since the ﬁ  rst edition of this chapter there has been a fair amount 
of research using the ‘big ﬁ  ve’ personality factors. There is evidence 
that the big ﬁ  ve factors can account for some, but not all of the 
pathological personality pathology described by the DSM system.
(28)
However the amount of information also depends on the speciﬁ  c

(28)
However the amount of information also depends on the speciﬁ  c 
instrument with some with more facets or detail being more able account for aspects of pathological personality. These would be instruments such as the NEO-PI
(29) and the ﬁ  ve factor model of 
Cloninger.(30) Also of possible greater utility are dimensional 
instruments which were designed from the start to measure 4.12.2 diagnosis and classification of personality disorders

SECTION 4  clinical syndromes of adult psychiatry 858
abnormal as well as normal personality. These include the Schedule 
for Non-adaptive and Adaptive Personality (SNAP)(31) and 
Dimensional Assessment of Personality Pathology (DAPP).(32) Also 
worth noting is a method by Widiger which combines a ﬁ  ve factor 
self-report with a ﬁ  ve factor interview in order to obtain more 
comprehensive personality information.(33)
2.  Other non-DSM personality measures from which DSM PD 
diagnoses can be derived.
There is one measure of DSM-IV personality which is derived from 
the interpersonal circumplex model. This is the Wisconsin Personality Disorders Inventory (currently in version IV).
(34) Although from a 
fairly different theoretical perspective from the DSM-IV it does have translations to make some DSM-IV diagnoses.
(35)
Another unique approach is the Shedler–Westen Assessment

(35)
Another unique approach is the Shedler–Westen Assessment 
Procedure which does not have a patient interview but ratherhas a clinician who knows the patient do a Q sort procedure. The process is based on distinguishing personality disorders basedon prototypes. This procedure can be translated into DSMpersonality diagnoses. It tends to create fewer diagnoses because 
the number of descriptors that can be used is limited by the Q sort procedure.
(36)
The Millon Clinical MultiAxial Inventory (now in version three)

(36)
The Millon Clinical MultiAxial Inventory (now in version three) 
is a very commonly used personality measure. It is now based on evolutionary theory according to its manual. One of the best vali-dated instruments in data-based terms. Unfortunately this data is mostly published in its own manual and not the journal literature. As the population that the instrument was validated on included some fairly severe disorders it is not clear how well the ﬁ  ndings 
would translate into a less severely ill population.
(37)
Assessment methods for personality 
disorders
Table 4.12.2.2 shows the main methods currently available for 
assessing all PDs. Additional instruments for assessing speciﬁ  ed 
PDs have also been developed—some of the methods listed are 
Table 4.12.2.2  Some commonly used assessment methods for all DSM personality disorders
Name of the instrument Author(s) (a)Method of assessment Number of

Name of the instrument Author(s) (a)Method of assessment Number of 
QuestionsTime required 
(minutes)
Diagnostic Interview for Personality Disorders (DIPD)Zanarini Semistructured interview with patient using DSM-IV 
criteria398 60–120
Dimensional Assessment of Personality 
Disorders (DAPP-BQ)Livesley & Jackson Dimensional based of normal and abnormal 
personality. Has components of DSM-IV PDs290 45
International Personality Disorder 
Examination (IPDE)Loranger et al. Semistructured interview with patient using ICD-10 and 
DSM-IV criteria537 150
Millon clinical Multiaxial Inventory 
(MCMI)Millon Self-report by patient using DSM-IV criteria 175 20–30
NEO Personality Inventory-Revised 
(NEO PI-R)Costa & McRae Comprehensive measurement of normal and abnormal 
personality traits.240 30–40
Personality Assessment
Schedule (PAS)Tyrer et al. Semistructured interview with informant (s) can derive

Schedule (PAS)Tyrer et al. Semistructured interview with informant (s) can derive 
ICD-10 and DSM-IV diagnoses.24 60
Personality Diagnostic Questionnaire 
–Revised (PDQ-4)Hyler et al. Self-report by patient or informant(s) using DSM-IV 
criteria99 30
Personality Disorders Interview-IV Widiger et al. Semistructured interview with patient using DSM-IV 
criteria325 60–120
Schedule for Nonadaptive and Adaptive 
Personality (SNAP)Clark Self report by patient using DSM-IV and dimensional 
criteria375 30–60
Shedler-Westen Assessment Procedure Westen & Shedler Clinician rated Q sort procedure. Gives abnormal 
traits, symptoms and defences and can generate 
DSM-IV diagnoses200 No interview, based 
of clinician knowledge 
of client.
Structured Clinical Interview for DSM-IV 
Personality Disorders (SCID-II)First & Gibbon Semistructured interview with patient using DSM-IV 
criteria303 60–90
Structured Interview for DSM

of client.
Structured Interview for DSM 
Personality Disorders-IV (SIPD)Pfohl et al. Semistructured interview with patient or informant(s) 
using DSM-III criteria337 90
 Temperament and Character 
Inventory (TPQ)Cloninger et al. Self-report by patient. Temperament and Character 
dimensions.240 30–40
Wisconsin Personality Disorders 
Inventory (WISPI)Klein et al. Self-report by patient using DSM-III-R criteria. 
Correlated with interpersonal object relation theory.214 30
(a) For speciﬁ  c references to each instrument please see references.(30, 31, and 33)

859
new, while others have been revised two or three times.(38,39) The 
following points related to these methods need to be mentioned.
1 The interview measures have generally shown a satisfactory 
inter-rater reliability, while test–retest reliability has not been well established. However, three methods do show some evidence of good test–retest reliability—the Personality Assessment Schedule ( PAS),
(40) the International Personality Disorder 
Examination ( IPDE ),(41) and the Structured Clinical Interview 
for Personality Disorders (SCID-II) .(42) Many of the methods 
have been standardized on psychiatric inpatient or outpatient populations; their applicability in epidemiological community studies is largely unknown.
(43,44)
2 The various measures tend not to agree with each other on 
speciﬁ  c diagnoses.(38,39) A measurement on one standardized 
instrument is not necessarily the same as the measurement on another.
3 Some authors, mostly developers of interview instruments, have

3 Some authors, mostly developers of interview instruments, have 
in the past stated that self-report measures are not as valid for the measurement and study of personality as interview measures. These arguments tend to be based on the ﬁ  nding that self-report 
instruments do not agree well with interview instruments, and that a PD diagnosis cannot be made without a clinical interview. The ﬁ  rst argument does not hold water, since none of the inter-
view instruments agree well with each other either. Whether self-report instruments can reliably diagnose a PD (as opposed to personality traits) is an open question. However, dimensional interview instruments have high test–retest reliability (some for as long as 30 years) and have been, and will continue to be, a valuable component of personality research, especially where the focus is on dimensions.

(45) Self-report instruments measuring 
DSM disorders tend to disagree with each other in a similar way to the interview instruments. In conclusion, the instrument chosen for any given clinical or research endeavour should reﬂ  ect 
the ability of the individual instrument to meet the speciﬁ  c needs 
of the project. Most researchers now believe that using a self-report, which may be more sensitive but less speciﬁ  c is a good 
prelude to a semi-structured interview measure.
4 Standardized testing of personality and clinician impression do 
not tend be in good agreement. This is due both to the tendency of instruments to report more disorders and for clinicians to use idiosyncratic criteria in their diagnoses.
(46,47)  Standardized meas-
ures are a must, however, if the data is to be used for research or public policy purposes.
5 Most personality measurement instruments are affected by the

5 Most personality measurement instruments are affected by the 
comorbid presence of a non-personality emotional disorder (Axis I disorder in the DSM system). Some structured interviews try to correct for this by asking patients about times when they were not suffering from an Axis I disorder; however, when the Axis I disorder is chronic, this may be difﬁ  cult to achieve.
(41,42)
This problem also affects the ability of questionnaires to differ-
entiate between current Axis I disorders and PDs, as this self-judgement of patients who are suffering from a psychiatric condition is frequently impaired.
(41) The PDE, PAS, and SCID-II 
may be less affected by this problem.
6 There is disagreement among experts about the use of infor-
mants. Many authors have argued that, besides the patient, a key informant should also be interviewed, given the likelihood

mants. Many authors have argued that, besides the patient, a key informant should also be interviewed, given the likelihood 
that many patients will not reply reliably to questions abouttheir personality and the possibility that informant ratingswill differ substantially from patient ones.
(41,48) However, even
if an informant is interviewed, it is often unclear which sourceto use to score the test if the interviewee and informantdisagree. This tends to reduce their value. More recent research indicates that informants may be of value if their informationis in certain areas that are easily observable to then and thenare incorporated into the evaluation process in a standar-dized way.
(49)
7 Discriminant validity refers to the ability of a diagnostic system 
and measurement system to diagnose non-overlapping disorders. Discriminant validity is not high with the ICD-10 and DSM-IV PDs.

(50) This means that it is the rule, rather the exception, that 
multiple personality diagnoses will be made: some studies have provided evidence of this assumption. For instance, in four studies that examined personality comorbidity in a total of 568 patients, the average percentage of multiple diagnoses was 85 per cent.
(51) T o what extent this reﬂ  ects the real coexistence of 
different disorders—with distinct patterns of symptoms, corre-lates, and course—or if it is simply the effect of an insufﬁ  cient 
discriminant validity of current diagnostic systems has still to be clariﬁ  ed.
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disorders: current research and treatments  (ed. J. Reich), pp. 3–20. 
Taylor & Francis, New Y ork.

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maladaptive personality traits. In Differentiating normal and abnormal 
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861
4.12.3 Speciﬁ  c types of 
personality disorder
José Luis Carrasco and Dusica Lecic-Tosevski
Cluster A personality disorders
Paranoid personality disorder
Pervasive suspiciousness, mistrust, hypersensitivity to criticism, 
and hostility are the essential features of paranoid personality dis-order. These individuals live a restricted emotional and interper-sonal life because they fear the malevolent intent of others. As a rule, paranoid people are ready to counter-attack, provoking repeated confrontations. In this way, they induce hostility and resentment in others.
The term paranoia may lead to some confusion if it is not 
properly delimited. Paranoid had been used as an adjective to label various delusional representations or syndromes. Kraepelin
(1)
differentiated paranoia as a distinct condition characterized by 
chronic and highly systematized delusional ideas (see Chapter 4.4). Schneider
(2) described people with this paranoid personality as

(2) described people with this paranoid personality as 
fanatic psychopaths, stressing their intensity, and rigidity in con-frontation with others. He denied any relationship with paranoia. Freud
(3) and other psychoanalysts construed the paranoid character 
as a pattern of mistrust and feeling of being attacked, based on distortions and externalization of the person’s inner world.
Paranoid personality disorder was included in DSM-III with 
criteria of suspiciousness, mistrust, hypersensitivity, and restricted affectivity. This last criterion does not appear in DSM-IV and ICD-10, since restricted affectivity is neither necessary nor speciﬁ  c 
for paranoid personalities. Instead, emphasis is placed on mistrust and sensitivity to setbacks. The DSM-IV criteria for paranoid personality disorder are shown in Table 4.12.3.1.
(a) Epidemiology

The prevalence of paranoid personality disorder is estimated at about 0.5 to 1 per cent in the general population and at 10 to 20 per cent among psychiatric patients. The disorder is more commonly diagnosed in males.
(b) Aetiology
This personality disorder has a familial relationship with delusional disorders and with schizophrenia,
(4) and has been included in the 
so-called schizophrenic spectrum.(5) Deﬁ cits in cortical dopamine 
activity may be associated with a poor conceptual organization that could in turn be responsible for suspiciousness and distorted interpretations.
(6)
Mistrust and lack of conﬁ  dence may reﬂ  ect deﬁ  cits arising 
in early developmental stages and resulting in a lack of basic self-conﬁ  dence.
(7) Lack of protective care and affective support in

(7) Lack of protective care and affective support in 
childhood could perhaps facilitate the development of paranoid features.
(c) Clinical picture
Paranoid individuals do not often ask for help from psychiatrists. They have no wish to be cured; instead, they believe that they have to be protected from other people’s hatred and attacks. Subjects 
with this personality disorder suspect that others are acting to harm, exploit, or deceive them. These suspections are based not on objective evidence, but on internal conviction and an attempt to ﬁ nd a rational explanation for the supposed wrongs.
Paranoids are reluctant to conﬁ  de in others; they tend to feel that

Paranoids are reluctant to conﬁ  de in others; they tend to feel that 
others are plotting against them, and that the enemy may be found in unexpected places. They do not readily tell others about their suspicions. The disorder may be manifested by irritability, unusual defensive or self-protective behaviours (e.g. locking doors and closing windows and curtains to avoid being spied on, and hiding papers or documents), or emotional detachment.
Paranoid people lack conﬁ  dence in others. They doubt the 
loyalty or trustworthiness of friends and partners, and check their 
behaviour repeatedly for evidence of malevolent intentions. They assume that others are not trustworthy, to the extent that they can-not believe it when friends demonstrate their loyalty. They with-hold personal or signiﬁ  cant information from friends, fearing that

it will be used maliciously against them. They do not form close friendships and are often isolated. When in trouble, paranoids do not expect help from friends or others close to them; instead, they expect to be attacked or ignored.
Many of the suspicious and distrustful attitudes of paranoids are

Many of the suspicious and distrustful attitudes of paranoids are 
perpetuated by their intense interpersonal sensitivity. They react intensely to any comment or event that may relate to them. Hidden meanings that are demeaning and threatening may be read into benign events or the remarks of others. Unintended errors by col-leagues or public servants are taken as deliberate attempts to harm or deceive them. Humorous remarks or jokes may be interpreted as attacks on their character. Paranoids are easily hurt, and their pride is easily damaged by minor critical comments or questioning. They are excessively preoccupied with attacks on their reputation or character, and minor slights may arouse major hostility and a Table 4.12.3.1 DSM-IV diagnostic criteria for paranoid personality 
disorder
A. A pervasive distrust and suspiciousness of others such that their motives 
are interpreted as malevolent, beginning by early adulthood and present in

disorder
are interpreted as malevolent, beginning by early adulthood and present in 
a variety of contexts, as indicated by four (or more) of the following
1  Suspects, without sufﬁ  cient basis, that others are exploiting, harming, or 
deceiving him or her
2  Is preoccupied with unjustiﬁ  ed doubts about the loyalty or 
trustworthiness of friends or associates
3   Is reluctant to conﬁ  de in others because of unwarranted fear that the 
information will be used maliciously against him or her
4  Reads hidden demeaning or threatening meanings into benign remarks 
or events
5 Persistently bears grudges, i.e. is unforgiving of insults, injuries, or slights6  Perceives attacks on his or her character or reputation that are not 
apparent to others and is quick to react angrily or to counterattack
7  Has recurrent suspicions, without justiﬁ  cation, regarding ﬁ  delity of 
spouse or sexual partner

B. Does not occur exclusively during the course of Schizophrenia, a Mood
Disorder With Psychotic Features, or another Psychotic Disorder and is not 
due to the direct physiological effects of a general medical condition.
Note  If criteria are met prior to the onset of Schizophrenia, add ‘Premorbid’, e.g. ‘Paranoid 
Personality Disorder (Premorbid)’4.12.3 specific types of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 862
counter-attack. They bear grudges and harbour hostile feelings for 
a long time, and are unwilling to forgive the insults, injuries, or slights that they think they have received.
(8)
Pathological jealousy is a common presentation of paranoid 
individuals. They have unreasonable doubts about the loyalty and faithfulness of their partners, based on little or no evidence. They may try to gather trivial and circumstantial facts to justify their beliefs. T o avoid betrayal they attempt to gain complete control of intimate relationships, continuously questioning, and challenging partners about their whereabouts and intentions.
The interpersonal world of paranoids is a consequence of their 
suspiciousness and distrust. They have difﬁ  culty in relating to

suspiciousness and distrust. They have difﬁ  culty in relating to 
others, especially with close relationships. Hostility is always present and can be manifested as excessive argumentativeness, recurrent complaint and confrontation, or hostile aloofness.
(8)
Although they may appear rational, unemotional, and cold, the affect of paranoids is labile and oversensitive and they may be hostile, stubborn, and sarcastic. This mixture of secretive, cold, hostile, and sarcastic behaviours often elicits a hostile response in others, which conﬁ  rms the paranoid person’s beliefs.
Paranoids blame others for their shortcomings. They are queru-
lous and quick to counter-attack, so that they may become involved in frequent litigation. Since they do not confide in others, paranoids need self-conﬁ  dence and a sense of autonomy and

lous and quick to counter-attack, so that they may become involved in frequent litigation. Since they do not confide in others, paranoids need self-conﬁ  dence and a sense of autonomy and 
independence. They need to control people who might be harmful. While they do not accept criticism, they are highly critical.
One group of paranoids are close to Schneider’s ‘fanatics’ .
(2) They 
have hidden grandiose fantasies of power and negative views of other people, especially those belonging to another group who come to be considered as natural enemies. They simplify issues and avoid any ambiguous perspective. Some form cults or other tightly knit groups with people who share their paranoid belief systems.
(d) Course
Paranoid features may be present in childhood and early adoles-cence in the form of hypersensitivity, social anxiety, poor peer rela-tionships, and eccentricity. These features sometimes elicit teasing from other children, which in turn may aggravate the paranoid attitudes.

In situations of stress, individuals with paranoid personality 
disorder may respond with brief psychotic episodes. During these episodes, they may have frank delusional ideas or distorted percep-tions. Some paranoid personality disorders are the premorbid state for a delusional disorder or even schizophrenia.
Individuals with this personality disorder may be at increased 
risk for agoraphobia, obsessive–compulsive disorder, and substance abuse or dependence. This perso nality disorder is often c o-diag nosed 
with schizoid, schizotypal, narcissistic, and avoidant personality 
(e) Differential diagnosis
Paranoid personality disorder should be distinguished from

Paranoid personality disorder should be distinguished from 
suspicious attitudes towards examination among immigrants, ethnic groups, or political groups. Members of these groups may display defensive and mistrustful behaviours owing to lack of familiarity with the language or the rules of a society, or in response to perceived neglect or rejection. Their behaviour may elicit further rejection from the majority, thus reinforcing the defensive behaviours.Paranoid personality disorder is distinguished from delusional 
disorder, paranoid schizophrenia, and depression with psychotic symptoms, all of which are characterized by periods of persistent psychotic symptoms. Paranoid personality disorder present before the occurrence of these syndromes should be diagnosed as ‘premorbid’ .
People with schizotypal personality disorder are suspicious, have

People with schizotypal personality disorder are suspicious, have 
paranoid ideas, and keep their distance from others. However, they also experience perceptual distortions and magical thinking, and are usually odd and eccentric. Schizoid personality disorder is characterized by aloofness, coldness, and eccentricity, but these individuals usually lack prominent suspiciousness or paranoid 
ideation. Individuals with avoidant personality disorder  are 
hypersensitive and do not conﬁ  de in others. However, their lack 
of conﬁ  dence is based on fear of being embarrassed or found inad-

equate rather than fear of other people’s malicious intentions. Some antisocial behaviour by paranoid individuals originates in a wish for revenge or counter-attack, rather a desire for personal gain as in antisocial personality disorder. Paranoid features are often present in narcissistic individuals who fear that their imperfections could be revealed. The differential diagnosis should be based on the predominance of persistent need of praise versus persistent suspiciousness and distrust.
(f) Treatment
Antidepressant and anxiolytic treatment may be useful for anxiety and depression resulting from a paranoid response to stressful situations. Low-dose antipsychotics may be indicated during brief psychotic episodes or when ideas of reference are present.

Psychological treatment is difﬁ  cult owing to the lack of insight. 
The approach is to attempt to gain the patient’s confidence, avoiding early confrontation of distorted ideas, followed by a slow gentle attempt at cognitive restructuring.
Schizoid personality disorder
Schizoid personality disorder is characterized by a persistent pattern of social withdrawal. Schizoid individuals show discomfort in social interactions and are introverted. They are seen by others as eccentric, isolated, or lonely. DSM-IV diagnostic criteria are shown in Table 4.12.3.2.
This type of personality became recognized in the ﬁ  rst two 
decades of the twentieth century. August Block’s description of the shut-in personality and Eugen Bleuler’s description of autism distinguished between shy and lonely persons and those who engage in relationships only in fantasy. Psychoanalysts included this term in their writings and developed an approach based on deﬁ cient object relations and individuation.

(9) Some schizoid 
personalities have probably been sweet children who were very easy to care for, although giving less joy to their parents and eliciting less stimulation and fewer expressions of emotion than more expressive children.
(7)
The epidemiology of schizoid personality disorder is not clearly established. Recent studies give a median prevalence of 0.5 to 1 per cent (see Chapter 4.12.5).
A familial association may exist between schizotypal personality disorder and schizophrenia.

863
People with schizoid personality disorder appear cold, reserved, 
distant, and unsociable. They lack involvement in everyday events and in the concerns of others. They rarely tolerate eye contact, usually give short answers, and appear uneasy when asked about emotions or feelings. However, they may invest much energy in abstract ideas such as those of mathematics or philosophy.
There is a characteristic lack of emotional expression and low 
energy. Speech is typically slow and monotonous, and seems to lack associated emotion. Affect is excessively serious or constrained, although some inner fear may be detected by an experienced clini-cian. If they try to be humorous, they usually give a child-like impression. Psychomotor activity tends to be lethargic, lacking gesture, and rhythmic movement. They may seem absorbed in insigniﬁ  cant matters, keeping quiet and not annoying anybody, as 
if in their own world. They do not express joy, anger, sadness, or

if in their own world. They do not express joy, anger, sadness, or 
other emotions. Interpersonal communication tends to be formal and impersonal, although not irrational. Threats, real or imagined, are dealt with by fantasized omnipotence or resignation. Aggressive acts are infrequent.
People with schizoid personality disorder characteristically seem 
to lack interest in the lives and concerns of others. When in a group, they stay unnoticed and detached, seeming indifferent to criticism or praise or to the reactions of others. Schizoids are attracted to solitary hobbies, and may be successful in lonely jobs that others ﬁ nd difﬁ  cult to tolerate. Many prefer working at night. Usually,

they do not seem to suffer because of this detachment and they have no desire for closeness or intimacy. They seldom have close friends or relationships, except with immediate relatives. Their sexual lives may be poor or exist only in fantasy, and some post-pone mature sexuality indeﬁ  nitely. They do not usually marry, 
although some, especially schizoid women, may passively agree to marriage. However, schizoid individuals may make emotional attachments with animals or inanimate objects.Schizoid personalities lack insight, and generally have a poorly 
developed sense of identity and a poor capacity for evaluating interpersonal events. They may appear to be self-absorbed and engage in excessive daydreaming. However, some schizoid individ-uals have original and creative ideas.
(d) Differential diagnosis
Schizoids have better occupational functioning than patients with schizophrenia  or schizotypal personality disorder , and, although

Schizoids have better occupational functioning than patients with schizophrenia  or schizotypal personality disorder , and, although 
isolated, can have successful careers. Schizophrenic patients exhibit delusional thinking or hallucinations and psychotic episodes. Schizotypal individuals show greater eccentricity and oddness than schizoids, and also have perceptual and thought disturbances including magical thinking.
People with paranoid personality disorder  may also show social 
detachment and lack close relationships. However, they show more social engagement than schizoids and may have a history of aggres-sive behaviour.
Emotional constraint is also present in obsessive–compulsive 
personality disorder , but obsessional patients are more involved in 
everyday life and concerns, and may be worried by criticism. People with avoidant personality disorder  are also detached and aloof.

everyday life and concerns, and may be worried by criticism. People with avoidant personality disorder  are also detached and aloof. 
However, although they actively avoid interpersonal contact because of fear of rejection or being found inadequate, they have an intense desire for close relationships.
(e) Course
Schizoid personality disorder is usually apparent in early childhood. As with all personality disorders, it is usually long-lasting; however, it is not necessarily lifelong although there is seldom any rapid or profound change. If their deﬁ  cits are moderate and social 
circumstances are favourable, some schizoids achieve social and vocational adaptation.
Although this personality disorder is sometimes a precursor 
of schizophrenia, the number of schizoid patients who go on to develop schizophrenia is unknown.

Because they lack insight and have little motivation for change, schizoids seldom seek treatment. Motivation for change may depend on life circumstances and external pressures.
Low-dose antipsychotic medication is useful in some situations. 
Antidepressants and psychostimulants have also been used with some positive effects.
The psychotherapy of patients with schizoid personality disorder 
must be based on gaining a therapeutic alliance. Unlike paranoid patients, they may become involved in therapy and reveal fantasies, imaginary friends, and fears of unbearable dependency. Ambivalence may appear because of fear of dependence on the therapist, who must keep the necessary distance to allow a tolerable relationship for the patient.
Social skills training is sometimes useful in improving their

Social skills training is sometimes useful in improving their 
awareness of social cues.
Schizotypia is a controversial term in psychiatry. The term was used by Kretschmer
(10) to denominate the phenotypic characters that 
antedated the development of schizophrenia. Nevertheless, the term schizotypal personality disorder was not included in psychiatric classiﬁ  cations until the publication of DSM-IIIR in 1987.
(11) Before Table 4.12.3.2 DSM-IV diagnostic criteria for schizoid personality 
disorder
A. A pervasive pattern of detachment from social relationships and a 
restricted range of expression of emotions in interpersonal settings, beginning by early adulthood and present in a variety of contexts, as indicated by four (or more) of the following
1  Neither desires nor enjoys close relationships, including being part 
of a family
2 Almost always chooses solitary activities3  Has little, if any, interest in having sexual experiences with another

of a family
2 Almost always chooses solitary activities3  Has little, if any, interest in having sexual experiences with another 
person
4 Takes pleasure in few, if any, activities
5 Lacks close friends or conﬁ  dants other than ﬁ  rst-degree relatives
6 Appears indifferent to the praise or criticism of others7 Shows emotional coldness, detachment, or ﬂ  attened affectivity
Disorder With Psychotic Features, another Psychotic Disorder, or a Pervasive Developmental Disorder and is not due to the direct 
physiological effects of a general medical condition
Note  If criteria are met prior to the onset of Schizophrenia, add ‘Premorbid.’ e.g. ‘Schizoid 
Personality Disorder (Premorbid)’.4.12.3 specific types of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 864
that date, schizotypal individuals were allocated either with schiz-
oids or with schizophrenics, and were usually labelled as latent schizophrenics or pseudoneurotic schizophrenics. However, the validity of this nosological entity is still controversial and, despite its acceptance in DSM-IV , ICD-10 does not recognize it as a sepa-rate personality disorder. Instead, ICD-10 includes the schizotypal syndrome among the psychotic disorders and not as a personality disorder, based on the biological afﬁ  nities of schizotypal individu-
als with other schizophrenic patients. DSM-IV diagnostic criteria are shown in Table 4.12.3.3.

Schizotypal personality disorder is present in 0.5 to 3 per cent of the general population, with no demonstrated differences between sexes. It is more commonly diagnosed in relatives of schizophrenic patients, and the incidence is much higher in monozygotic than in dizygotic twins (33 per cent versus 4 per cent).
(4)
(b) Clinical picture
The essential feature of schizotypal individuals is a pattern of pecu-liarity and oddness in interpersonal relationships with resulting social detachment and lack of close relationships. Because of their distorted reality processing schizotypal individuals feel intensely uncomfortable in the presence of others. Conversely, others feel uneasy in the presence of schizotypals because of their unusual ways of thinking and expressing emotions.
Like schizoids, schizotypals have a decreased desire for intimate

Like schizoids, schizotypals have a decreased desire for intimate 
contacts, although they may sometimes express unhappiness about their lack of relationships. As a consequence they do not have close friends or conﬁ  dants other than relatives. They experience intense anxiety in social situations with unfamiliar people. They can inter-
act if necessary, but they prefer to keep aloof because they feel different and are not interested in the concerns of others. Their anxiety in these situations is not based on feelings of inadequacy or fear of humiliation. Rather, it is due to suspicion of the motivation of others, and therefore it is not alleviated as time passes and the situation becomes more familiar. Thus schizotypals feel progres-sively worse and more reluctant to conﬁ  de in other people.
Individuals with schizotypal personality disorder often have 
ideas of reference that is interpretations of casual events as having speciﬁ  c and unusual meanings related to themselves. However,

ideas of reference that is interpretations of casual events as having speciﬁ  c and unusual meanings related to themselves. However, 
these ideas do not achieve the pathological conviction of delusions. Similarly, these individuals may be preoccupied with superstitions or paranormal phenomena. They may feel that they may read other people’s thoughts or inﬂ  uence their behaviour by the power of 
thought. Their magical thinking is often manifested by ritualized behaviours aimed at avoiding harmful events.
Perceptual disturbances are frequent in schizotypal personality 
disorder. An experience of a sixth sense is typical, with the ‘ability’ 
to notice someone’s presence. Distorted perceptions are present 
in the form of sounds perceived as calling voices or shadows trans-formed into ﬁ  gures and faces.
Thought processing and speech are characteristically affected.

Thought processing and speech are characteristically affected. 
Speech may be constructed in an unusual and idiosyncratic way-generally loose, digressive, or vague, but without actual derail-ment or incoherence. Responses may be either excessively concrete or far too abstract, and words may be used in unusual ways.
The interpersonal relationships of schizotypal individuals are 
primarily affected by paranoid and suspicious ideation. They may believe that colleagues at work want to damage their reputation. In addition to the social anxiety of these individuals, this leads to 
a stiff and constricted contact and affect. They are considered odd 
and eccentric by others: they have peculiar mannerisms, dress in an unusual and unkempt manner, adopt extravagant postures and clothing combinations, do not obey normal social conventions, and generally avoid eye contact.
(b) Course

(b) Course
Schizotypal features may be present in childhood and adolescence in the form of solitariness, academic underachievement, hypersen-sitivity, and bizarre fantasies. Schizotypals do not seek treatment because of their personality disorder, but rather because of the presentation of associated depression, dysphoria, and anxiety. In response to stressful situations, these patients may experience transient psychotic episodes lasting from minutes to hours. In some cases, clinical symptoms and duration reach the degree of brief psychotic disorder, schizophreniform disorder, or schizophrenia, with the schizotypal personality disorder as the premorbid state. The prevalence of major depressive episodes is notoriously high, as is co-diagnosis with paranoid, schizoid, avoidant, and borderline personality disorders.
Delusional disorder ,schizophrenia , and mood disorder with 
psychotic symptoms  have to be excluded based on the greater

psychotic symptoms  have to be excluded based on the greater 
intensity and persistence of psychotic symptoms.
In childhood, it can be difficult to distinguish schizotypal 
personality disorder from other forms of disorders characterized by odd behaviour, isolation, eccentricity, and peculiarities of Table 4.12.3.3  DV-IV diagnostic criteria for schizotypal personality 
disorder
A. A pervasive pattern of social and interpersonal deﬁ  cits marked by acute 
discomfort with, and reduced capacity for, close relationships as well as by cognitive or perceptual distortions and eccentricities of behaviour 
beginning by early adulthood and present in a variety of contexts, as 
indicated by ﬁ  ve (or more) of the following
1 Ideas of reference (excluding delusions of reference)
2  Odd beliefs or magical thinking that inﬂ  uences behaviour and is

2  Odd beliefs or magical thinking that inﬂ  uences behaviour and is 
inconsistent with subcultural norms (e.g. superstitiousness, belief in 
clairvoyance, telepathy, or ‘sixth sense’; in children and adolescents, 
bizarre fantasies or preoccupations)
3 Unusual perceptual experiences, including bodily illusions
4  Odd thinking and speech (e.g. vague, circumstantial, metaphorical. 
overelaborate, or stereotyped)
5 Suspiciousness or paranoid ideation6 Inappropriate or constricted affect
7 Behaviour or appearance that is odd, eccentric, or peculiar
8 Lack of close friends or conﬁ  dants other than ﬁ  rst-degree relatives
9  Excessive social anxiety that does not diminish with familiarity and 
tends to be associated with paranoid fears rather than negative 
judgements about self

Disorder With Psychotic Features, another Psychotic Disorder, or a 
Pervasive Developmental Disorder.
Note  If criteria are met prior to the onset of Schizophrenia, add ‘Premorbid’, e.g. ‘Schizotypal 
Personality Disorder (Premorbid)’.

865
language. These include autistic disorder ,Asperger’s disorder ,
and some language disorders . The differentiation with communi-
cation disorders is based on the prominence of language symptoms in these children and the compensatory efforts to communicate by gesture and other means. Autism and Asperger’s disorder present an even more intense social isolation and indifference, stereotyped 
behaviours and interests.
Paranoid  and schizoid personality disorders  lack the perceptual 
and speech impairment of schizotypal personality disorder, as well as the marked eccentricity and oddness. Avoidant personality 
disorder , while including social anxiety and isolation, differs from 
schizotypal personality disorder in that avoidants have an intense desire for closeness, which is constrained by fear of rejection. Schizotypals do not have a desire for relationships. Borderline 
personality disorder  has a high rate of co-occurrence with schizo-

typal personality disorder and frequently the two disorders cannot be differentiated. Brief psychotic episodes in people with border-line personality disorder are more dissociative-like and generally follow affective shifts in response to stress or frustration. Social isolation in borderline personality patients is generally due to repeated interpersonal failures rather than a persistent lack of desire for relationships and intimacy.
Finally, schizotypal personality disorder must be diagnosed in 
the cultural context of the patient. It should be noted that some perceptual peculiarities and magical beliefs may be due to culturally determined characteristics. For example, mind reading, voodoo, shamanism, evil eye, and so on should not be considered as personality disorders in some cultural areas.
(d) Treatment

Low-dose antipsychotic medication may be useful for ideas of ref-erence, perceptual disturbances, and other psychotic-like symptoms. Antidepressants are effective when depressive states are associated.
The psychological management of schizotypals should include 
a prolonged period of gaining the confidence of the patient. However, a particularly careful approach must be adopted owing to the peculiar thought processing of these patients.
Cluster B personality disorders
Antisocial personality disorder

Antisocial personality disorder is characterized by a pattern of disregard for the safety and the rights of others, without feeling remorse. Individuals with this disorder are unreliable, manipula-tive, incapable of lasting relationships, and unable to conform to social norms. The disorder starts early (before the age of 15), is pervasive, and manifests in variety of contexts. Although social deviance is one of the core features of antisocial personality disorder, it is not synonymous with criminality. Antisocial person-ality disorder uncomplicated by other disorders is not often met in clinical settings, except forensic psychiatry. However, owing to its impact on family and social environment, it has major public health signiﬁ  cance and has been extensively studied in academic 
psychiatry, psychoanalysis, law, sociology, theology, and literature.
The description of antisocial personality in the last 1970s was

The description of antisocial personality in the last 1970s was 
mainly based on criminal behaviour
(12) and the disorder was 
conceptualized as synonymous of criminality. Later classiﬁ  cations 
modiﬁ  ed this approach and focused on the personality traits and 
emotional patterns described in classic descriptions included the classic personality traits leading to the current DSM-IV and 
ICD-10 classiﬁ  cation criteria for antisocial personality disorder. 
(Tables 4.12.3.4 and 4.12.3.5).
A prevalence rate of about 3 per cent is consistently found in the general population, and it is more frequent in males than females, with sex ratios ranging from 2:1 to 7:1. It is more common among younger adults, people living in urban areas and lower socio-economic groups.
(13)Table 4.12.3.4 SM-IV diagnostic criteria for antisocial personality 
disorder

disorder
A. There is a pervasive pattern of disregard for and violation of the rights of 
others occurring since age 15 years, as indicated by three (or more) of the following
1  Failure to conform to social norms with respect to lawful behaviours as 
indicated by repeatedly performing acts that are ground for arrest
2  Deceitfulness, as indicated by repeated lying, use of aliases, or conning 
others for personal proﬁ  t or pleasure
3 Impulsivity or failure to plan ahead
4  Irritability and aggressiveness, as indicated by repeated physical ﬁ  ghts 
or assaults
5 Reckless disregard for safety of self or others6  Consistent irresponsibility, as indicated by repeated failure to sustain 
consistent work behaviour or honour ﬁ  nancial obligations
7  Lack of remorse, as indicated by being indifferent to or rationalizing 
having hurt, mistreated, or stolen from another
B. The individual is at least age 18 years

C. There is evidence of conduct disorder with onset before 15 yearsD. The occurrence of antisocial behaviour is not exclusively during the course 
of Schizophrenia or a Manic Episode.
Table 4.12.3.5 ICD-10 diagnostic criteria for disocial personality 
disorder
Personality disorder, usually coming to attention because of a gross disparity 
between behaviour and the prevailing social norms, and characterized by
  (a) callous unconcern for the feelings of others  (b)  gross and persistent attitude of irresponsibility and disregard for 
social norms, rules and obligations
  (c)  incapacity to maintain enduring relationships, though having no 
difﬁ  culty in establishing them
  (d)  very low tolerance to frustration and a low threshold for discharge 
of aggression, including violence

  (e)  incapacity to experience guilt and to proﬁ  t from experience, 
particularly punishment
  (f)  marked proneness to blame others, or to offer plausible 
rationalizations, for the behaviour that has brought the patient into conﬂ  ict with society
There may also be persistent irritability as an associated feature. Conduct 
disorder during childhood and adolescence, though not invariably present, 
may further support the diagnosis.
Includes:  amoral, antisocial, psychopathic, and sociopathic personality 
 (disorder)
Excludes:  conduct disorders, emotionally unstable personality disorder4.12.3 specific types of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 866
The aetiology of antisocial personality disorder is complex and 
multifactorial, involving biological, early developmental, and social determinants.
Twin, adoption, and family studies have demonstrated that 
genetic factors strongly contribute to the development of antisocial 
personality.
(14) Antisocial personality in males is often associated 
with hysteria in women of the same family which suggests that the two conditions might be alternative expressions of the same genetic endowment, belonging to ‘spectrum conditions’ .
(15) Longitudinal 
studies of hyperactive children have reported high rates of later (adult) antisocial behaviour, and have suggested a ‘developmental’ relationship between antisocial behaviour and childhood hyperac-
tivity. 
Aggression in antisocial personality disorder is associated with

tivity. 
Aggression in antisocial personality disorder is associated with 
indexes of reduced brain serotonin activity such as low levels of the serotonin metabolite 5-hydroxyindole-acetic acid in the cerebro-spinal ﬂ  uid and
(16,17) low platelet monoamine oxidase activity. 
Reports on minimal brain dysfunctions resulting on frontal-lobe deﬁ ciencies and lack of inhibition have also been described.
Parental deprivation, inconsistent maternal care, family violence, 
and severe childhood physical) abuse have been reported as strong predictors for development of antisocial personality disorders.
(12,18)
Social disintegration and chronic criminality can cause episodic 
antisocial behaviour, reﬂ  ecting a normal adaptation to an abnormal 
social environment.(19) However, the multifactorial origin of the 
antisocial personality disorder and its early onset and manifesta-tions indicate that it cannot be attributed to cultural conﬂ  icts and 
social determinants.

(c) Clinical features and diagnosis
Patients with antisocial personality disorder often appear quite normal, charming, and understanding. However, their history reveals disturbed functioning in the domains of behaviour and self-concept, love and sexuality, interpersonal relations, and cognitive style.
(20)
Reckless behaviour unaffected by punishment is typical of 
antisocial individuals, who are also exploitative, manipulative, demanding, and lacking in a sense of responsibility. An easy-going hedonistic attitude may be interrupted by rage, cruelty, and violence. The absence of internalized moral values is manifested by lying, truancy, running away from home, thefts, ﬁ  ghts, substance 
abuse, and illegal activities may be typical experiences, beginning in early childhood.

An impaired control of impulses and a reduced ability to antici-
pate the negative consequences of behaviour is typical associated to a marked intolerance to anxiety. Antisocial individuals are ego-centric, and unable to feel genuine guilt and remorse. They exhibit intense and persistent anger usually expressed as hostility towards others and they have an incapacity for reﬂ  ective mourning or 
sadness. Frequent suicide threats and attempts are also common, as 
is somatic preoccupation.
Interpersonal relationships of antisocial subjects are character-
ized by manipulation, exploitation, instability and incapacity for love, and comprehension. Sexual perversions, abuse, and pae-dophilia are frequent. They display deﬁ  cient parenting and social 
dysfunction, and resistance to authorities is pronounced.
The cognitive style of antisocial subjects is characterized by

The cognitive style of antisocial subjects is characterized by 
glibness, superﬁ  ciality of knowledge, and paranoid view of reality.(d) Comorbidity and differential diagnosis
Antisocial personality disorder is frequently comorbid with depres-
sion , which usually has atypical features. Bipolar disorder  (manic 
phase) and mental retardation  (learning difﬁ  culties) should be 
excluded. Substance abuse may be comorbid from childhood, 
and antisocial behaviour may be secondary to premorbid alcohol-
ism type 2. Atypical schizophrenic disorder  (pseudopsychopathic 
schizophrenia), temporal-lobe epilepsy , or a limbic-lobe syndrome
should also be excluded.
The presentation of antisocial and criminal behaviour in border-

line personality disorder is frequent. However, borderline behav-iours are marked by intense affective instability and reactivity and may show some remorse or guilt. Unlike antisocial patients, borderline personality disorders do not lack the capacity for inti-macy and emotional investment of others and do not show sadistic behaviours. Self-aggression and suicide attempts are much more prevalent among BPD than in antisocial personality.
Aggressive and deﬁ  ant behaviours are often present in histrionic 
personality disorder. Although some aetiologic relationship among both disorders might be possible, as described above, histri-onic patients are more impulsive and emotionally driven than antisocial and display intense emotions related with attachments and losses.
(e) Course and prognosis

Antisocial behaviour is most pronounced in early adult years, and gradually decreases with age. Professional motivation and establishing a stable couple or partnership may have beneﬁ  cial 
effects. Maturation of the personality might also take with depression or hypochondriasis emerging when rage and aggression are abandoned. Substance abuse and promiscuity are risky behaviours for developing HIV infection.

Medication is used to deal with incapacitating symptoms, such as anxiety, rage, depression, and somatic complaints. Selective serotonin reuptake inhibitors, lithium, carbamazepine, clonazepam, and other anticonvulsants have been used to control aggressive behaviour but the effects are much less pronounced than in borderline personality disorder or intermittent explosive disorder. Psychostimulants such as methylphenidate may be useful if there is evidence of attention-deficit hyperactivity disorder. Benzodiazepines are contraindicated since they might cause behavioural disinhibition.
Efﬁ cacy of psychotherapy is very little in antisocial patients. Fear 
of intimacy causes difﬁ  culties in establishing a therapeutic alliance, 
which should be oriented to ﬁ  nd alternative defence mechanisms 
to acting-out and to self-defeating behaviours. Therapeutic communities based on the principles outlined by Maxwell Jones
(21)

(21)
with a general social adjustment as a main task, might give positive results.
Borderline personality disorder (BPD) is the denomination of a syndromal picture characterized by intense affective instability and impulsivity together with an unstable sense of self-identity. It is often manifested by impulsive self-aggression and suicide attempts, substance abuse, chronic feelings of emptiness, and persistent pattern of severely unstable interpersonal relationships.

867
The term borderline was ﬁ  rst used by Stern(22) in 1938 to denom-
inate a group of syndromes placed in the border between neuroses and psychoses and included also the current label of schizotypal personality disorder and a group of disorders currently classiﬁ  ed as 
psychotic disorders. Only some decades later the term borderline began to be understood as a disorder of character
(23) and intro-
duced in DSM-III as a personality disorder, after being separated from schizotypal personality disorder.
Borderline personality disorder derives but is not fully 
equivalent to the concept of borderline personality organization developed by Kernberg.
(24) BPO is a stable permanent state based 
on three criteria: diffuse identity, primitive defence mechanisms (splitting, denial, and projective identiﬁ  cation), and intact reality 
testing. This personality organization can be found not only in BPD but also in other severe personality disorders and Axis I conditions.

Borderline personality disorder itself can be found in association 
with so many Axis I and Axis II disorders that its validity as an independent diagnostic category is still weak compared with other personality disorders. Some authors have suggested that borderline personality disorder reﬂ  ects rather a state of severely impaired per-
sonality function than a discrete diagnostic entity.
(25) Others have 
suggested that BPD is an atypical variant of affective disorder and should be included in the affective disorder spectrum.
(26) In the 
ICD-10, this disorder is named as ‘emotionally unstable personality disorder’ , with two subtypes: impulsive and borderline. Borderline subtype is specifically linked to the presence of self-identity weakness and diffusion.

The number of people suffering from borderline personality disorder ranges from 1.5 to 5 per cent of general population with wide differences between studies because of lack of reliable measures. The prevalence is greater in clinical samples of patients at the outpatient clinics, ranging form 10 to 15 per cent. The disor-der is more common in women than in men and is commonly initiated between 18 and 35 years old.
(27)
Several factors have been associated with a higher prevalence of borderline personality disorder, including genetic, biological, and developmental findings.
(28) Family studies indicate that 
parents of patients with BPD have a greater incidence of mood disorders but not of schizophrenia. Additionally, there is also high family incidence of antisocial personality disorder and alcoholism.
Among the biochemical findings, those indicating a brain 
serotonin deﬁ  ciency are the more consistent. Reduced levels of

serotonin deﬁ  ciency are the more consistent. Reduced levels of 
5-hydroxyindoleacetic acid in cerebrospinal ﬂ  uid and blunted 
prolactin response to serotonin agonists have been demonstrated in association with impulsive aggression, which is a core feature of BPD.
(29) Hypothalamic-pituitary—adrenal axis dysfunctions, 
suggesting increased feedback inhibition, as well as increased sensi-tivity of some areas of the amigdala, have been reported in samples of BPD patients. Current available data suggest that BPD might be associated with abnormal emotional reactivity in the limbic areas and insufﬁ  cient regulatory function at the cingulated and prefron-
tal areas of the brain.
(30)
The role of childhood trauma in the development of borderline 
personality disorder could be crucial. Higher incidence of childhood traumatic experiences, both for sexual/physical abuse or

(30)
personality disorder could be crucial. Higher incidence of childhood traumatic experiences, both for sexual/physical abuse or 
for neglect, has been demonstrated in these patients.(31) Other 
proposed developmental factors include deﬁ  ciencies in self and 
identity development linked to attachment failures with parental ﬁ gures in the early developmental phases.
(32,33)
The onset of BPD needs the interaction of predisposing factors, 
both biological and developmental, and environmental precipi-tants. BPD patients seem to be extremely sensitive to frustrations in the intimate relationships, which are commonly detected at the onset of the disorder.
Impulsivity and affective instability, self-aggression, identity disturbance, and unstable/intense interpersonal relationships are the most characteristic manifestations of borderline personality disorder.

Identity weakness and diffusion explain several aspects of 
borderline personality disorder (Table 4.12.3.6). It is clinically manifested by contradictory character traits and sense of disconti-nuity of the self and feelings of emptiness.
(34) Probably related with 
this is also the intolerance to be alone and the desperate efforts to avoid abandonment by signiﬁ  cant others. The chronic feeling of 
emptiness is recurrently intensiﬁ  ed and unbearable leading to drug 
abuse and self-defeating behaviours.
The affect of borderline patients is chronically dysphoric and 
irritated. Their unstable mood is a mixture of depressed affect, anger, loneliness, and emptiness. Impulsive–aggressive behaviour is a core feature of borderline personality disorder and is related with this abnormal affective state.
Cognitive style of borderline patients are easily suggestible and

Cognitive style of borderline patients are easily suggestible and 
frequently change their decisions. Things and people are seen in black-and-white terms. Transient and brief psychotic episodes are frequent in BPD patients associated with unstructured stressful 
Table 4.12.3.6 DSM-IV diagnostic criteria for borderline personality 
disorder
A pervasive pattern of instability of interpersonal relationships, self-image, and 
affects and marked impulsivity beginning by early adulthood and present in a 
variety of contexts, as indicated by ﬁ  ve (or more) of the following
1  Frantic efforts to avoid real or imagined abandonment. Note:  Do not 
include suicidal or self-mutilating behaviour covered in Criterion 5
2  A pattern of unstable and intense interpersonal relationships characterized 
by alternating between extremes of idealization and devaluation
3  Identity disturbance: markedly and persistently unstable self-image or sense 
of self

of self
4  Impulsivity in at least two areas that are potentially self-damaging 
(e.g spending, sex, substance abuse, reckless driving, binge eating). Note:  Do not include suicidal or self-mutilating behaviour covered 
in Criterion 5
5  Recurrent suicidal behaviour, gestures, or threats, or self-mutilating 
behaviour
6  Affective instability due to a marked reactivity of mood (e.g. intense 
episodic dysphoria, irritability, or anxiety usually lasting a few hours and only rarely more than a few days)
7 Chronic feelings of emptiness8  Inappropriate intense anger or difﬁ  culty controlling anger (e.g. frequent 
displays of temper, constant anger, recurrent physical ﬁ  ghts)
9 Transient stress-related paranoid ideation or severe dissociative symptoms4.12.3 specific types of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 868
situations. Psychotic symptoms may have a typical dissociative-like 
nature or present as transient self-referential ideation. Rejection sensitivity and suspiciousness usually colours the interpretations of behaviours of others.
Borderline patients are both intensely dependent and hostile 
towards signiﬁ  cant others. Interpersonal relationships are unstable, 
intense, demanding, clinging, and characterized by alternation between extremes of idealization and devaluation, deriving from the defence mechanism of splitting. Infatuations are followed by devaluation of love objects. There is a tendency towards promiscuity and perversions.
(d) Comorbidity and differential diagnosis
Borderline personality disorder is frequently comorbid with affec-
tive disorders  (major depression, dysthymia, and ‘double depres-
sion’), anxiety disorders ,somatization disorder ,post-traumatic 
stress disorder , and alcohol abuse .

Differential diagnosis has to be made with type II bipolar 
disorder . Bipolar patients more often present emotional lability 
from sadness/apathy to euphoria while BPD patients are character-ized by intense and reactive affective instability and shift rather from sadness to tolerable dysphoria. Intermittent explosive disorder also shows impulsive and aggressive behaviours but lacks identity disturbances and affective instability typical of BPD. Mild mental retardation might have intense irritability, lability, and impulsive/aggressive behaviour but lacks chronic feelings of empti-ness and self-identity diffusion. Transient psychotic episodes and 
stress-related referential ideas of BPD should be differentiated from 
pervasive psychotic-like experiences of schizotypal personality disorder.

Borderline personality disorder has been shown to be associated 
with most personality disorders, especially with those from the dramatic cluster. The high prevalence of comorbid personality disorders may result from overlapping of diagnostic criteria or reﬂ ect the conﬁ  rmation that there is the underlying borderline per-
sonality organization of all severe personality disorders. However, some features like chronic feelings of emptiness, self-mutilation, short-lived psychotic episodes, intense and episodic drug abuse, and intense ambivalent dependency in close relationships suggest a primary diagnosis of BPD.
(e) Course and outcome

Borderline patients often experience profound dysfunction inmany important aspects of life including education, jobs, partner relationships, and marriage. Alcohol and psychosexual problemsare also frequent. Repeated suicide attempts and premature death from suicide are frequent complications of borderline personality dis order; therefore suicidal gestures and intentions should bealways taken seriously. It has been reported that 8 to 10 per cent per cent of all persons with borderline personality disorder commitsuicide.
(35)
The long-term outcome of borderline patients has not been 
studied, but the diagnosis is rarely made in patients aged over 40. It is speculated that neural structures and defence mechanisms mature with age and that these changes, together with social learn-ing, reduce symptomatology.

Pharmacotherapy is targeted to symptoms such as affectivechanges (depression, anxiety, rage, dysphoria), cognitive distur bances (brief psychotic episodes or interpretative distortions), and impul-
sive behavioural dyscontrol.
(36) New antidepressants, including 
SSRIs and venlafaxine, have shown positive effects in treating a broad spectrum of acute symptoms, including depression, hostility, irritability, anxiety, obsessive–compulsive symptoms, suicidal attempts, and impulsivity. Antipsychotics and anticonvulsants may help some patients, even in the absence of EEG or organic changes. There are still no clinical predictors for efﬁ  cacy, therefore, a prag-
matic approach is indicated with patients being treated with two or three drugs in a sequential trial.
(36) Suicidal and abusive use of 
drugs prescribed and non-compliance may be serious problems for treatment of BPD.
Various psychotherapeutical modalities are used, including

Various psychotherapeutical modalities are used, including 
psychodynamic psychotherapy, supportive psychotherapy, and dialectical–behavioural therapy.
A more structured form of psychoanalytic approach, involving 
expressive psychotherapy and an active role of psychotherapist have been proposed speciﬁ  cally for BPD. The aims are confronta-
tion of maladaptive defences and interpretation of transference, focusing on the ‘here and now’ , without attempting the achieve-ment of a full genetic reconstruction.
(37)
Short-term psychotherapy is useful for managing crises or intro-

(37)
ducing long-term forms of therapy. Supportive psychotherapy is suggested for more fragile borderline patients, who are prone to serious regression in treatment. In practice, supportive therapy, with a psychoeducational component, has been the most frequently used form of treatment for borderline personality disorder. It is also possible to combine elements of intensive dynamic therapy with supportive therapy, depending on the ego strength of the patients.
(38)
Dialectical–behavioural therapy(39) is based on cognitive tech-
niques associated with reality confrontation. The major aim is emotional self-regulation and behavioural self-control and is par-ticularly indicated for control of suicidal and impulsive behaviours and treatment of emotional reactivity.
Histrionic personality disorder
(a) Deﬁ  nition
Histrionic personality disorder derives from the concept of

Histrionic personality disorder derives from the concept of 
hysterical personality, supported by descriptive literature and clinical tradition but not so much by valid empirical research.It is characterized by excessive emotionality and attentionseeking, and by dramatic, colourful, and extroverted behaviour. Egocentric, dependent, and demanding interpersonal relationships are typical of this disorder, which begins in early adulthood andis present in a variety of contexts. The DSM-IV and ICD-10diagnostic criteria for this disorder are shown in tables 4.12.3.7and 4.12.3.8.
It was included in scientiﬁ  c medicine by Kraepelin,
(40) who 
described multiple symptoms, including capricious and inconsis-tent behaviour, histrionic exaggeration, and a life of illness, which captured the core pattern of the illness. Freud
(41) recognized the

(41) recognized the 
relationship between hysterical neurosis and what he called the ‘erotic personality, whose major goal in life is the desire to love or above all to be loved’ . Psychoanalytic theorists often distinguish hysterical (‘healthier’) and histrionic (‘sicker’) personalities, where the latter has borderline organization and is an exaggeration of the former. Differences between the two concepts are shown in Table 4.12.3.9.

869
(b) Epidemiology
The prevalence is found to be 2 to 3 per cent of the general popula-
tion and 10 to 15 per cent in clinical settings.(42) No signiﬁ  cant 
difference has been found in terms of race and education and is more frequently diagnosed in women than in men. However, some cultural biases associated with sex role stereotypes and emotional expressiveness could lead the lower diagnostic rates in men.
(43)
(c) Aetiology
Some studies suggest that histrionic personality runs in families, but evidence for a biological or learning transmission is not yet consistent.
(44) Traits such as extraversion, emotional expression, 
and reward dependence have a strong genetic origin and might be constitutional. Biological ﬁ  ndings associated with impulsivity, such 
as serotonin deﬁ  ciency, can be found in histrionic patients with

as serotonin deﬁ  ciency, can be found in histrionic patients with 
marked emotional instability and impulsive behaviours. It has been proposed that histrionic personality in women is genotypically linked to antisocial personality in men.
(45)
From a development perspective, histrionic personality is 
considered to be a result of abnormally intense attachment with parental ﬁ  gures. The erotization component of this attachment in the oedipical phase was classically emphasized in the psycho-
analytic research, although recent approaches suggest that there oral/dependent factors, derived from anomalies in earlier phases are of greater importance in the development of the disorder.
(46)
(d) Clinical features and diagnosis
Emotionality, dramatization, exhibitionism, egocentricity, and 
sexual provocativeness are typical of histrionic personalities. However, behavioural expression is not always as manifested and other emotional and cognitive aspects may help for diagnosis.

Histrionic individuals are inappropriately seductive and aggres-
sively demanding. They are self-centred, crave for novelty and excitement, and are prone to temper tantrums. Histrionic subjects are hyperemotional and impulsive, but their emotional enthusiasm is superﬁ  cial and transient and their mood is labile. They describe 
their emotions in an inappropriate and exaggerated way in an attempt to obtain attention. Histrionic individuals are suggestible, demanding, accusative, and guilt inducing. In intense stressful situations they can show a dissociative-type of indifference and infantilism.
Histrionic personalities are inclined to sexualize all non-sexual

Histrionic personalities are inclined to sexualize all non-sexual 
relations, often indiscriminately, not only with a chosen partner but also with a wide variety of persons in various social, occupa-tional, and professional relationships. Pseudosexuality is often accompanied by frigidity. A romantic outlook or a superﬁ  cially 
adoring attitude often disguises needs for dependency and emo-tional attachment to a signiﬁ  cant protective ﬁ  gure. Sicker individu-
als may be promiscuous, and may engage in multiple perverse activities.Table 4.12.3.7 DSM-IV diagnostic criteria for histrionic personality 
disorder
A pervasive pattern of excessive emotionality and attention seeking, 
beginning by early adulthood and present in a variety of contexts, as indicated 
by ﬁ  ve (or more) of the following
1  Is uncomfortable in situations in which he or she is not the centre of 
attention
2  Interaction with others is often characterized by inappropriate sexually 
seductive or provocative behaviour

attention
3 Displays rapidly shifting and shallow expression of emotions
4 Consistently uses physical appearance to draw attention to self
5 Has a style of speech that is excessively impressionistic and lacking in detail
6  Shows self-dramatization, theatricality, and exaggerated expression of 
emotion
7 Is suggestible, i.e. easily inﬂ  uenced by others or circumstances
8 Considers relationships to be more intimate than they actually are
Table 4.12.3.8 ICD-10 diagnostic criteria for histrionic personality 
disorder
Personality disorder characterized by at least three of the following:
  (a) self-dramatization, theatricality, exaggerated expression of emotions
  (b) suggestibility, easily inﬂ  uenced by others or by circumstances
  (c) shallow and labile affectivity

(a) self-dramatization, theatricality, exaggerated expression of emotions
  (d)  continually seeking for excitement, appreciation by others, and 
activities in which the patient is the centre of attention
  (e) Inappropriate seductiveness in appearance or behaviour  (f ) Overconcern with physical attractiveness
Associated features may include egocentricity, self-indulgence, continuous 
longing for appreciation, feelings that are easily hurt, and persistent 
manipulative behaviour to achieve own needs
Includes:  hysterical and psycho-infantile personality (disorder)Table 4.12.3.9 Types of histrionism
Hysterical personality Histrionic personalitya
Neurotic personality 
 organizationBorderline personality organization
Integrated identity Diffuse identity

Predominance of repression Predominance of splittingIntact reality testing Intact reality testing (proneness to distortion)Integrated superego Marked superego defectsStrongly bonded families Disturbed, often broken familiesSteady educational and 
 vocational careersErratic careers
Capable of maintaining 
 long-term friendshipsChaotic interpersonal relationships
Suggestible in triangular 
 relationshipsDiffuse suggestibility
Inauthenticity Multiple identiﬁ  cations
Changing moods Frequent dysphoriaSexual inhibition Promiscuity, perverse tendenciesCompetitiveness with the 
 same sexLess differentiated behaviour toward sexes
Genital traits Oral/pregenital traits
a Includes hysteroid, hysteriform, oral hysteric, and sick hysteric personality disorders. 
After Akhtar.(31)4.12.3 specific types of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 870
Cognitive style is global, impressionistic, and diffuse, and lacks 
sharpness of detail. Non-verbal communication is better than verbal, speech is inhibited, and education is often superﬁ  cial. 
Speech may show malapropisms or slips of the tongue.
The basic belief of histrionic personalities is that others should 
be impressed, and their basic strategy is dramatization. They blossom when they are the centre of attention and are highly disappointed when they are not, and draw attention to themselves by acting and speaking in a charming ﬂ  irtatious way. Histrionic 
individuals quickly respond to others in an intimate way, often treating superﬁ  cial acquaintances as if they were friends.
(e) Comorbidity and differential diagnosis
There is current evidence that somatization disorder  (Briquet’s 
syndrome) and conversion disorder  can occur in conjunction 
with histrionic personality disorder, as well as dissociative

disorder  and brief reactive psychosis .(21) Differential diagnosis 
should not be difﬁ  cult, because histrionic personality disorder
is a lifelong disturbance with a chronic course, unlike Axis I disor-ders which are episodic. Hypomanic and manic states  may be 
accompanied by seductive behaviour and exaggerated expression of emotions, but can be distinguished from histrionic personalityby their episodic nature and the presence of other characteristic symptoms.
A great deal of overlap has been found between histrionic per-
sonality disorder and other Axis II disorders , deﬁ ned by DSM-IIIR 
criteria; of these, the borderline, narcissistic, antisocial, and depen-dent personality disorders are the most frequent.
Borderline patients have more chaotic interpersonal relation-

ships, make frequent suicide attempts, and are prone to regressive episodes of a psychotic nature. Histrionic individuals share sexual promiscuity, corruptibility, shallow emotions, and a self-centred attitude with antisocial personalities.
(47) However, they do not 
show sustained, calculated, and ruthless disregard of social norms. Narcissists may also seek attention, but they want to be admired for their superiority while histrionic persons are clinging and depen-dent. Unlike narcissists, histrionic individuals have empathy for other persons. However, the features of the two disorders can be combined.

Depressive symptoms, suicide attempts, and frequent use of medical services are common. Histrionic personality may gradually improve with age, as if a maturation of histrionic infantilism occurs over the years.
Depressive and anxious symptoms are frequent in histrionic 
personality disorder and can be alleviated with the use of antide-
pressants and anxiolytic medications. However, extreme care should be taken for treatment due to the vulnerability of these patients for medication abuse and non-compliance.
Supportive therapy is indicated for acutely distressed histrionic 
patients, as well as for those at the sicker end of the continuum. Psychoanalytic techniques in histrionic patients
(47) are oriented to 
clariﬁ  cation of the patient’s covert inner feelings. Patients are often

clariﬁ  cation of the patient’s covert inner feelings. Patients are often 
demanding, want to take a special place in the therapist’s life, and act out during therapy sessions, threatening to abandon treatment or undertake dangerous actions. Clear limits should be set and demanding dependent behaviour should not be rewarded.Narcissistic personality disorder
Narcissistic personality disorder is characterized by an exaggerated sense of self-importance with a lack of sustained positive regard for others. Grandiosity (in fantasy or behaviour) and constant craving 
for admiration and external gratiﬁ  cation are additional features 
of this disorder. They are present in a variety of contexts and begin by early adulthood.
(a) Historical perspective
The term narcissism originates from the Greek myth of Narcissus who was infatuated with his own reﬂ  ection in the mirror-lake.

The term narcissism originates from the Greek myth of Narcissus who was infatuated with his own reﬂ  ection in the mirror-lake. 
Its contemporary usage has many meanings and implications, from its colloquial usage denoting self-centred persons, often with pejorative connotations, to a pathological clinical syndrome. Despite the popularity of the construct, there is still considerable disagreement on the aetiology and phenomenology of narcissistic personality disorder. There is little empirical evidence regarding its description, clinical utility, and validity.
A narcissistic personality has a pathological grandiose self, which 
hides a diffuse and aimless inner identity. Kernberg argues that self-hatred, rather than self-love, lies at the root of pathological narcissism, and distinguishes between narcissism in the broad sense and the speciﬁ  c pathological structures of the narcissistic personality.

According to Kernberg, narcissistic patients function on a border-
line level. Malignant narcissism,
(37) which develops when primitive 
aggression inﬁ  ltrates the pathological grandiose self, lies at the 
extreme end of a continuum. It is a combination of narcissistic personality disorder, antisocial behaviour, egosyntonic aggression or sadism directed against others, and a strong paranoid orientation (Table 4.12.3.10).
Narcissistic personality disorder was officially accepted in 
DSM-III. Somewhat reﬁ  ned criteria were adopted in DSM-IV 
(Table 4.12.3.11), because some studies showed a substantiallack of diagnostic reliability when the DSM-III criteria wereused. Narcissistic personality disorder is not included in ICD-10, being mentioned only in the category ‘Other speciﬁ  c personality
Table 4.12.3.10  Types of narcissism
Normal Pathological Malignant
Infantile Grandiose self-image Grandiose self-image
Regression or ﬁ  xation to 
 infantile narcissistic goals

 infantile narcissistic goals 
 in personality disorders 
 (personality traits)Low self-esteem
Primitive defences
Superego defects
Borderline organizationAggression
Paranoid traits
Antisocial behaviour
Explosive traitsBorderline organization
Adult
Healthy self-esteem 
 regulated by 
 normal self-structure
Integrated object 
 representations
Capacity for deep object 
 relations
Integrated superego
After Kernberg.(32,37)

871
The prevalence of narcissistic personality disorder in the community 
has been found to be around 0.5 per cent.(48) Its prevalence in 
clinical populations is estimated to range from 1 to 3 per cent, and is more frequently diagnosed among males.
Although no demonstrating evidence is yet available, some aspects of narcissism might be related with inappropriate seeking for excitement and reward and associated to monoamine function abnormalities at the mesolimbic reward systems.
Severe frustration with early objects is considered important in 
the defensive genesis of narcissistic personality disorder. Behind the compensatory grandiose self, a hungry and inferior real self-resides, as the core problem of narcissistic personality disorder. Often, high parental expectations and harsh criticism of the child is present in the family.
(d) Clinical characteristics and diagnosis

Narcissistic patients only seek for help when depressed or involved in interpersonal problems.
An often engaging and attractive appearance masks intense 
preoccupation with self-regard and an unusual absence of concern for others. Narcissistic individuals may be energetic, capable of consistent work, and socially successful, but this is done in order to obtain admiration. Their successes provide no inner satisfaction and always end with frustration and a feeling of emptiness. Narcissistic grandiosity is often masked by opposing tendencies (false modesty, social aloofness, and a pretended contempt for status). Pathological lying is frequent.
Narcissistic individuals feel bored when the external glitter wears

Narcissistic individuals feel bored when the external glitter wears 
off and there are no new sources to feed their self-esteem, which is extremely fragile. Lacking emotional depth, they do not have genu-ine feelings of sadness or longing. Anger and resentment laden with vengeful wishes are frequent as a reaction to injured self-esteem. 
Chronic intense envy is present, as are defences against such envy, particularly devaluation, omnipotent control, and narcissistic withdrawal. They have frequent mood swings, and hypomanic exaltation is often part of the clinical picture.
Narcissistic persons are unable to fall in love, and only have 
fantasies of ideal love. Sexuality is trivialized, and intercourse is a purely physical pleasure. Promiscuity, perverse fantasies, devalua-
tion of objects, and boredom in relationships are frequent.
Interpersonal relationships are frequently manipulative and

Interpersonal relationships are frequently manipulative and 
exploitative. They idealize people whom they expect to feed their narcissism, but depreciate and treat with contempt others (often former idols) from whom they do not expect to receive anything. They lack empathy and concern for others, who are welcome only as an applauding crowd and as mirrors of success.
Typical defence mechanisms (omnipotence, omniscience, 
intellectualization, rationalization, idealization, and devaluation) are derived from splitting.
Narcissistic personality disorder is often comorbid with major depression, dysthymic disorder, substance abuse, and anorexia nervosa. Patients meeting criteria for narcissistic disorder have a high overlap with histrionic, borderline, and antisocial person-
ality disorders , and also with schizotypal, paranoid, and passive–
aggressive personality disorders .

Narcissistic personality disorder may display some features of 
bipolar disorder (manic and hypomanic episodes). However, the mood swings are of limited duration and change rapidly, while insight is maintained and the general integrity of the personality is preserved.
Narcissistic personality disorder is strikingly similar to border-
line personality disorder. Phenomenologically, grandiosity is the 
best discriminator between the two disorders.
(49) In narcissistic 
personality disorder, there is also better impulse control, greater social adjustment and anxiety tolerance, less frequent suicide attempts, and less danger of regressive fragmentation and psychotic episodes.
Narcissistic individuals, especially those manifesting malignant

Narcissistic individuals, especially those manifesting malignant 
narcissism, may demonstrate antisocial behaviour. However, antisocial individuals are more impulsive and less capable of con-centrating on work and career, and they are devoid of guilt feelings. Similarities with histrionic and obsessive–compulsive personalities are superﬁ  cial, since people with these disorders have a capacity for 
empathy and a concern and love for others.
Patients often become depressed or defensively hypomanic during middle age, when their internal life gradually deteriorates owing to a vicious circle of frustrations and disappointments and dimin-ishing narcissistic supplies. Hypochondriasis and anxiety disorders are frequent complications.
Anxiolytic agents and antidepressants may be helpful for alleviating target episodes of mood and anxiety symptoms.
(i) Psychotherapy

Individual psychotherapy is aimed to the analysis of idealizing transference and interpretation of self-g randiosity. However, during Table 4.12.3.11 DSM-IV diagnostic criteria for narcissistic 
A pervasive pattern of grandiosity (in fantasy or behaviour), need for 
admiration, and lack of empathy, beginning by early adulthood and present 
in a variety of contexts, as indicated by ﬁ  ve (or more) of the following
1  Has a grandiose sense of self-importance (e.g. exaggerates achievements 
and talents, expects to be recognized as superior without commensurate 
achievements)
2  Is preoccupied with fantasies of unlimited success, power, brilliance, beauty, 
or ideal love
3  Believes that he or she is ‘special’ and unique and can only be understood 
by, or should associate with, other special or high-status people

by, or should associate with, other special or high-status people 
(or institutions)
4 Requires excessive admiration
5  Has a sense of entitlement, i.e. unreasonable expectations of especially 
favourable treatment or automatic compliance with his or her expectations
6  Is interpersonally exploitative, i.e. takes advantage of others to achieve his 
or her own ends
7  Lacks empathy, i.e. is unwilling to recognize or identify with the feelings 
and needs of others
8 Is often envious of others or believes that others are envious of him or her
9 Shows arrogant haughty behaviours or attitudes4.12.3 specific types of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 872
the ﬁ  rst stages only supportive therapy is recommended with
interpretations delayed until conﬁ  dent and integrated attachment 
with therapist is achieved.
The treatment of narcissistic individuals inevitably arouses 
serious countertransference problems, because of the emotional detachment, demanding behaviour, and devaluative actions of nar-cissistic patients. The therapist should have worked through his or her own narcissism and retain an empathic and non-judgemental attitude.
Cluster C personality disorders
Avoidant personality disorder
Avoidant personality disorder was ﬁ  rst introduced into psychiatric 
classiﬁ  cation in DSM-III.(11) Before this, such patients were included 
among the schizoid or dependent patients. The emphasis on avoidant behaviour as a consequence of an intense sensitivity to rejection led to the differentiation of this new personality type.

The characteristic behaviour of the avoidant personality is active 
isolation from the social environment. Unlike schizoids, who are characterized by passive social isolation, avoidant subjects turn inward to protect themselves because they are extremely sensitive to rejection.
(50) They desire interpersonal relationships but they 
avoid any chance of disapproval. Thus, only relationships that are likely to lead to complete non-critical acceptance are established. The extreme sensitivity to criticism is based on intense feelings of inferiority, poor self-concept and low self-esteem. This disorder is termed anxious personality disorder in ICD-10, since anxiety is considered to be the basic affective feature. The DSM-IV criteria for avoidant personality disorder are shown in Table 4.12.3.12.

The prevalence of avoidant personality disorder is estimated to be less than 1 per cent in the general population, but almost 10 per cent in clinical populations. No differences between sexes are found.
Some familial transmission is possible, perhaps involving learning and identiﬁ  cation, but genetic transmission may also be involved.
(51)
The biological mechanisms involved in anxiety disorders and social phobia may have a role in the development of this personal-
ity disorder. It has been suggested that hypersensitivity of brain areas involved in the separation-anxiety response and overactivity of serotonin limbic neuronal circuits may underlie the avoidant temperament trait.
(51)
Psychosocial factors mediate the extent to which biological

(51)
Psychosocial factors mediate the extent to which biological 
vulnerability is expressed. Children who are belittled, criticized, and rejected by parents have decreased self-esteem, resulting in social avoidance. These problems are reinforced and perpetuated at school and may generate the expectation of rejection from everyone.
(50)

(50)
Avoidant people are characterized by extreme shyness. They appear distant from others and do not express wishes, demands, or opinions. However, this behaviour contrasts with an extreme internal need for warmth and closeness. This contradiction is explained by an exaggerated sensitivity to rejection by others. People with this personality disorder are easily hurt and humiliated by comments from others, which they misinterpret as degrading and disapproving. They tend to be shy, quiet, and inhibited. They say nothing rather than risk being wrong, and they react strongly to any possible indications of mockery or criticism. They usually appear anxious, self-doubting, and insecure when speaking, often use self-defeating expressions, and try to please others. Their tense and fearful 
demeanour may elicit ridicule from others, which conﬁ  rms their

demeanour may elicit ridicule from others, which conﬁ  rms their 
insecurity. They are concerned with reacting to scrutiny by blush-ing or crying, which is a cause of further interpersonal avoidance. These patients often choose occupations where no social interac-tion is needed, and strongly avoid talking in public. The avoidant person lacks intimate relationships with friends or sexual partners unless they anticipate non-critical acceptance.
Patients with avoidant personality disorder perceive themselves

Patients with avoidant personality disorder perceive themselves 
as inept and inadequate, and assume that they are unattractive. They tend to see others as negative and potentially harmful. They are inattentive and repeatedly distracted by intrusive thoughts, but they attend intensely to signals of rejection. These people tend to make negative evaluations of situations and exaggerate risk. They have a low tolerance for dysphoric affects, which they avoid by escaping. Escape from reality through fantasy is their usual way of satisfying their needs and relieving frustration.
At interview they may be quite open if they feel accepted. This 
happens when good rapport is made, which is often easier in clinical than in social situations. However, social limitation
outside the ofﬁ  ce may be intense. Avoidant patients usually feel 
ashamed about many aspects of their lives and are excessivelyself-critical, although most of the concerns expressed seem to be trivial.
(d) Course

(d) Course
Avoidant personality disorder may follow childhood fear of strang-ers and shyness and isolation during school years. However, most shyness in childhood gradually dissipates in adolescence. When it evolves into avoidant personality disorder, the shyness may worsen in adolescence when social and interpersonal relationships become more complex and demanding. The disorder tends to remit or to become less evident in older people.
Avoidant personality disorder is often associated with depressive 
episodes, dysthymia, and anxiety disorders, particularly social phobia.Table 4.12.3.12 DSM-IV diagnostic criteria for avoidant personality 
disorder
A pervasive pattern of social inhibition, feelings of inadequacy, and to negative 
evaluation, beginning by early adulthood and present in a variety of contexts,

disorder
evaluation, beginning by early adulthood and present in a variety of contexts, 
as indicated by four (or more) of the following
1  Avoids occupational activities that involve signiﬁ  cant interpersonal contact, 
because of fears of criticism, disapproval, or rejection
2  Is unwilling to get involved with people unless certain of being liked
3  Shows restraint within intimate relationships because of the fear of being 
shamed or ridiculed
4  Is preoccupied with being criticized or rejected in social situations
5  Is inhibited in new interpersonal situations because of feelings of 
inadequacy
6  Views self as socially inept, personally unappealing, or inferior to others7  Is unusually reluctant to take personal risks or to engage in any new 
activities because they may prove embarrassing

873
It is often difﬁ  cult to differentiate avoidant personality disorder 
and social phobia of the generalized type. Impairment and distress due to the phobic situations is more intense in social phobia, which may have started in middle adulthood rather than adolescence. 
It is not clear whether the disorders are alternative manifestations 
of the same condition, or are separate disorders.
Hypersensitivity to rejection and criticism, low self-esteem, and 
feelings of inadequacy are also features of dependent personality disorder. While the avoidant patient avoids contact, the dependent patient focuses on being cared for. However, the disorders often co-occur and must be diagnosed together.
Schizoid and schizotypal personality disorder are also character-
ized by social isolation. However, avoidants want to have relation-
ships and suffer for their isolation, while schizoids and schizotypals accept isolation.

People with paranoid personality disorders lack conﬁ  dence in 
others. However, avoidants do not conﬁ  de in others because they 
fear being found inadequate, whereas paranoids fear malicious intent.
Anxiety and hypersensitivity to rejection may improve with anxio-lytic medication, β-blockers, monoamine oxidase inhibitors, and 
antidepressant medication. Medication should be combined with psychological treatment based on reinforcing assertiveness and self-esteem, and restructuring cognitive distortions concerning the self and others. Conscious and unconscious dependency needs should be addressed.
Dependent personality disorder (JLC)

Individuals with this disorder show a persistent and global pattern of behaviours directed at avoidance of the loss of intimate others. T o attain this goal, they relinquish their own needs, opinions, expression of feelings, and even their self-identity. In exchange, they get others to take over responsibility for major areas of their lives and to protect them. Their self-concept is characterized by weakness and helplessness, while others are perceived as powerful and protective.
These people were formerly included in different classiﬁ  catory 
categories. They belong to the abulic type of Kraepelin and of 
Schneider
(2) and were considered as immature personalities.
(a) Aetiology
Classic hypotheses attributing dependent personality to ﬁ  xation in 
oral phase of psychosexual development have given way to others indicating that the cause is rather deprivation than overgratiﬁ  ca-
tion in the oral phase.

Dependent personality was recognized ﬁ  rst in DSM-III.
(11) The 
description has changed little in DSM-IV (Table 4.12.3.13) and ICD-10.
(52) The crucial feature in both systems is the urgent need 
of patients to be cared for by others, with dependence, attachment, and fear of abandonment. Lack of self-conﬁ  dence was required in 
DSM-III, but was eliminated from recent classiﬁ  cations because it 
is not speciﬁ  c to this disorder.
Dependent patients are passive. They rarely express needs or feel-
ings, especially those that are sexual or aggressive. They tend to avoid responsibilities or decisions in major areas of their lives, such 
as work and ﬁ  nancial or interpersonal relationships. Instead they

as work and ﬁ  nancial or interpersonal relationships. Instead they 
get others, particularly family or partner, to decide for them or to provide continuous guidance. They depend on others (often one other person, usually the partner or a parent) to decide where they should go, what they should do, and even which clothes they should wear. They manifest self-doubt, pessimism, and a need for affection. They lack aggressiveness and appear helpless. The depen-dent patient avoids jobs that demand taking responsibility and managing others, and becomes anxious when forced into such situ-ations. These patients seek intensely for companionship and do not tolerate being alone. They may function at an adequate level if in a close and protective relationship, but when left alone they are unable to survive. They believe that they are incapable of function-ing independently and require constant assistance. They do not ini-
tiate projects, but wait for others who, they believe, will do them

tiate projects, but wait for others who, they believe, will do them 
better. However, dependent individuals can perform such tasks for other people whom they want to please and to whom they want to attach themselves.
They accept unpleasant tasks, are self-sacriﬁ  cing, and tolerate 
verbal, physical, or sexual abuse. Abusive relationships may be accepted as long as the attachment is preserved and is not exces-sively distorted.
An excessive and unrealistic fear of abandonment is constant in 
dependent individuals. When an intimate relationship is terminat-ed by separation or death, dependent individuals urgently seek another person who will provide the care and support they seek. Thus they become rapidly and indiscriminately attached to other persons when left alone.
These people are pessimistic, self-doubting, and have low self-

esteem. They belittle their capacities and successes and present themselves as inept. They take criticism as a proof of their inept-ness and conﬁ  rmation of their lack of self-conﬁ  dence.Table 4.12.3.13 DSM-IV diagnostic criteria for dependent 
A pervasive and excessive need to be taken care of that leads to submissive 
and clinging behaviour and fears of separation, beginning by early adulthood and present in a variety of contexts, as indicated by ﬁ  ve (or more) of the following
1  Has difﬁ  culty making everyday decisions without an excessive amount of 
advice and reassurance from others
2 Needs others to assume responsibility for most major areas of his or her life
3  Has difﬁ  culty expressing disagreement with others because of fear of loss of 
support or approval. Note  Do not include realistic fears of retribution

4  Has difﬁ  culty initiating projects or doing things on his or her own (because 
of a lack of self-conﬁ  dence in judgement or abilities rather than a lack of 
motivation or energy)
5  Goes to excessive lengths to obtain nurturance and support from others, to 
the point of volunteering to do things that are unpleasant
6  Feels uncomfortable or helpless when alone because of exaggerated fears of 
being unable to care for himself or herself
7  Urgently seeks another relationship as a source of care and support when a 
close relationship ends
8  Is unrealistically preoccupied with fears of being left to take care of himself 
or herself4.12.3 specific types of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 874
(c) Epidemiology
Recent studies have found a median prevalence of 0.7 per cent (see 
Chapter 4.12.5). Although dependent personality disorder is diag-nosed more frequently in women, structured interviews have not shown signiﬁ  cant differences between the sexes. Cultural factors 
may affect the reported prevalence, as passivity, politeness, and 
submission are normal in some societies.
(d) Course
Dependent personality features present in adolescence may evolve positively in adulthood or lead to a personality disorder. Dependent individuals are at increased risk of depressive, anxiety, and adjust-ment disorders, particularly in relation to loss of close relation-ships. Dependent personality disorder may follow separation anxiety in childhood, or chronic physical illnesses in childhood requiring long periods of care and attention.

Dependent personality disorder has some similarities with histri-onic personality disorder. Histrionic patients, like dependent patients, adjust their conduct to please other people. Their lives are centred in these others. However, people with histrionic personality disorder obtain attention and care by seductive or manipulative behaviours, whereas people with dependent personality disorder wait passively for others to care for them.
(7)
Like people with avoidant personality disorder, dependent individ-
uals may feel devastated by minor criticism or lack of attention from others. However, they lack the sense of embarrassment and social shyness of the avoidant, and fear loneliness or abandonment.
People with dependent and borderline personality disorders 
share an excessive fear of abandonment. However, borderline individuals react to separation with feelings of emptiness and rage, and are demanding, in contrast with the submissive and appeasing

share an excessive fear of abandonment. However, borderline individuals react to separation with feelings of emptiness and rage, and are demanding, in contrast with the submissive and appeasing 
attitude of dependent individuals, which is directed towards ﬁ  nd-
ing another person to provide support.
Dependent personality disorder must be differentiated 
from normal dependent behaviours in speciﬁ  c life situations; for 
example, elderly people with chronic or debilitating disease may become dependent.
Pharmacological treatment is indicated only when depressive or anxiety symptoms are present, especially when associated with separation or loss.
In psychotherapy, the therapist must avoid the development of 
excessively dependent attachments. Self-conﬁ  dence and self-esteem

excessively dependent attachments. Self-conﬁ  dence and self-esteem 
should be enhanced and the patient helped to enjoy the feeling of personal autonomy and independence. Cognitive restructuring and social skills training are often useful in bringing these changes about.
Obsessive–compulsive (anankastic) 
While DSM-IV labels this personality disorder as obsessive–
compulsive personality disorder (Table 4.12.3.14), ICD-10 prefers 
the term anankastic, previously used in European psychiatry to refer to fearful, insecure, and compulsive individuals. The cardinal 
feature of this disorder is an exaggerated and pervasive attempt to 
control. Anankastic patients need to control those who are close to them, to control every uncertainty, and to control their own

control. Anankastic patients need to control those who are close to them, to control every uncertainty, and to control their own 
thoughts and emotions. The anankastic lacks an internal sense of security and tries to make the external world totally predictable. The anankastic is afraid of his own internal aggressive drives and avoids free emotional expression. Others perceive this kind of personality as characterized by inflexibility and stubborn inefﬁ  ciency.
The prevalence of obsessive–compulsive personality disorders is 
about 1 per cent in community samples and up to 10 per cent in psychiatric patients, especially those with depressive and anxiety disorders. It is most frequent among males. Some obsessive–compulsive traits are sanctioned in some cultures, and a personality disorder should not be diagnosed unless the traits are markedly beyond the average for the culture.

Biological factors and learning seem to be involved in the aetiology of obsessive–compulsive personality disorder. The personality may be partly inherited.
(53) Early psychodynamic theories linked obses-
sive personality to the anal phase of psychosexual development between the ages of 2 and 4, when libidinal drives come into con-ﬂ ict with parental attempts to socialize the child, especially in 
sphincter control and toilet training. Later psychoanalytic theory
(54)
emphasized earlier manifestations of the child’s autonomy versus parental wishes. The expression of drives and emotions, including anger, is shaped by parental responses and may evoke shame and criticism.
This dynamic sequence is reinforced in societies which are 
strongly inﬂ  uenced by the Protestant work ethic, in families where 
individual emotions are subordinated to the group, and in societies in which open expression of emotions is discouraged.Table 4.12.3.14 DSM-IV diagnostic criteria for obsessive–

compulsive personality disorder
A pervasive pattern of preoccupation with orderliness, perfectionism, and 
mental and interpersonal control, at the expense of ﬂ  exibility, openness, and 
effciency, beginning by early adulthood and present in a variety of contexts, 
1  Is preoccupied with details, rules, lists, order, organization, or schedules to 
the extent that the major point of the activity is lost
2  Shows perfectionism that interferes with task completion (e.g. is unable 
to complete a project because his or her own overly strict standards are not met)
3  Is excessively devoted to work and productivity to the exclusion of 
leisure activities and friendships (not accounted for by obvious economic 
necessity)

4  Is overconscientious, scrupulous, and inﬂ  exible about matters of morality, 
ethics, or values (not accounted for by cultural or religious identiﬁ  cation)
5  Is unable to discard worn-out or worthless objects even when they have 
no sentimental value
6  Is reluctant to delegate tasks or to work with others unless they submit to 
exactly his or her way of doing things
7  Adopts a miserly spending style toward both self and others; money is 
viewed as something to be hoarded for future catastrophes
8  Shows rigidity and stubbornness

875
The behaviour of an obsessive–compulsive personality has 
been consistently described as one of orderliness. The patient is preoccupied with details, and pays attention to rules, procedures, schedules, and punctuality. Patients with obsessional personalities 
often produce their own detailed lists of symptoms and are annoyed 
if any item is neglected or misinterpreted. They repeat actions and check for mistakes, despite the inconvenience and annoyance that result from this behaviour. As a consequence, their conduct is frequently inefﬁ  cient. For example, the combination of unproduc-
tive perfectionism and rigidity may lead to difﬁ  culty in ﬁ  nishing 
a written report on time because of excessive correction and rewriting. Since this striving for perfection and order is time 
consuming, other areas of their lives often appear disorganized. 
One room or one desk drawer may fall into disarray, or parts of their social or family lives may be disorganized.

People with obsessive–compulsive personality focus on work 
and productivity. It is difﬁ  cult for them to take vacations or even to 
have free time. They do not enjoy leisure activity, which they may consider a waste of time. Often, they need to take work home to alleviate their anxiety. Hobbies and leisure pursuits become for-mally organized activities. They insist on perfect performance of sports or games and transform them into a serious task requiring careful organization and hard work. Leisure activities may be an unpleasant experience for the others involved, owing to the insistence on rules and standards.
Stubbornness is another characteristic of these people. They

Stubbornness is another characteristic of these people. They 
need things to be done in their way, and realistic arguments do not usually make them change their insistence. They need others to submit to their way of doing things, and often believe that no one can do the tasks as perfectly as they can. They give detailed instruc-tions, insisting that their way is the only way of doing things, and are irritated if others suggest alternatives. Therefore, they generally insist in doing everything themselves and are unable to delegate, which increases their inefﬁ  ciency at work. Paradoxically, their 
stubbornness is associated with doubt. Indecisiveness is a constant 
characteristic unless they have structured guidelines. They fear

characteristic unless they have structured guidelines. They fear 
making mistakes or misjudgements, and delay repeatedly until they have enough data to take what they consider the only right decision. When rules do not dictate the correct answer to a problem or when procedures for tasks are not laid down, decision-making or task initiation may become a lengthy and painful process.
People with this personality disorder are characterized by exces-
sive conscientiousness and scruples. They are inﬂ  exible about 
matters of morality, ethics, or values. Moral principles and stan-dards of performance have to be followed rigidly, and respect for authority and rules is absolute. Failure to do these things leads to irritation, anger, and self-criticism.
These people are stingy and mean, and often live with standards

These people are stingy and mean, and often live with standards 
far below their actual socio-economic status. They dislike spend-ing, believing that money should be saved in case of future difﬁ culties. They have great difﬁ  culty in discarding worn-out or 
worthless objects, believing that they might be useful some day. They may hoard objects such as newspapers or broken appliances, even when they have no sentimental value.
These people are humourless and lack spontaneity of emotional 
expression. Usually they do not express anger directly. However, they are often angry in situations in which they are unable to control the behaviour of themselves or others. Anger is generally 
manifested by indirect aggressive acts (such as leaving a small tip or not providing minor help when expected). Their management of anger is closely related to their attitude of dominance–submission towards authority ﬁ  gures. They may be excessively submissive to a

person in authority whom they respect, but obstructive with an authority ﬁ  gure whom they do not respect.
The affect of the obsessive person is controlled and stilted. It is 
not ﬂ  at or blunted, but constricted. They do not laugh or cry, and 
feel uncomfortable with people who express their feelings. Their mood is usually serious but may appear anxious or depressed. In a clinical interview they may sit in a stiff unnatural posture, and seldom make spontaneous comments about their emotions. They usually relate their history in a pedantic and circumstantial manner. If interrupted by a question from the doctor, they have to finish their monologue before answering. When asked about feelings, they answer with lists of facts and circumstances. They can label emotions and feelings, but are unable to display them.
In summary, obsessive personalities love order, neatness, and

In summary, obsessive personalities love order, neatness, and 
sameness, and hates novelty, spontaneity, and change. They need control, security, and certainty, and avoid creativity, art, and excitement. They mitigate anxiety by following strict rules and repress emotional expression by avoiding spontaneity. They fear their inner fragile and aggressive emotional world.
(d) Course

(d) Course
Like other personality disorders, obsessive–compulsive personality disorder is present in early adulthood and tends to be persistent and constant. However, some adolescents with marked obsessive traits become warm, loving, and tender adults. On the other hand, intense obsessional traits in adolescence are occasionally a premor-bid stage of schizophrenia (‘pseudoneurotic schizophrenia’). The developmental relationship between obsessive–compulsive person-ality disorder and obsessive–compulsive disorder is controversial. In the past, it was suggested that most obsessive–compulsive personality disorder evolved to a full obsessive–compulsive dis-order, indicating that the two syndromes were expressions of the same basic disorder. More recent investigations
(55) indicate

(55) indicate 
that most obsessive–compulsive disorder patients do not have a comorbid obsessive–compulsive personality disorder. A variety of psychiatric disorders may present in a patient with obsessive personality, but depressive and anxiety disorders are the most com-mon, followed by phobic, somatoform, and obsessive–compulsive symptoms. Hypochondriacal syndromes are commonly found in obsessive individuals when they lose control of situations.
Persons with this personality disorder may do well in jobs that 
demand working with detail, order, and structured procedures, and may adjust to interpersonal relationships with submissive spouses. However, they are particularly vulnerable to unexpected changes in their occupational and social environment. Late-onset depression is a common occurrence in obsessive–compulsive personalities.
The main difﬁ  culty in diagnosing obsessive–compulsive personality

The main difﬁ  culty in diagnosing obsessive–compulsive personality 
disorder is to differentiate it from obsessive–compulsive disorder. The latter diagnosis is made when occupational and personal func-tioning is severely impaired as a consequence of doubt, indecisive-ness, hoarding, or any other obsessive behaviour. In many, but not all, cases of obsessive personality, the traits and behaviours 4.12.3 specific types of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 876
are egosyntonic and no resistance is present, in contrast with 
obsessive–compulsive disorder.
The perfectionism of obsessive personalities may be present in 
narcissistic personality disorder. However, narcissistic individuals tend to believe that they have achieved perfection, while obsessive individuals tend to be highly critical of their own achievements.
Social detachment and the lack of empathy and warmth 
may suggest schizoid personality disorder. However, obsessive indi-viduals constrain their emotional expression to keep control of a situation, while schizoids lack the fundamental capacity for affective display or intimacy.
Not all individuals with obsessive traits have obsessive–compul-
sive personality disorder. Obsessive traits can be adaptive in some situations; it is only when they are maladaptive, inﬂ  exible, and 
persistently cause functional impairment that a personality disorder be diagnosed.

Pharmacological treatment may be tried in patients with anxiety and distress due to intense doubts, indecisiveness, and scruples. Benzodiazepines may alleviate tension in these cases. Antidepressants with a serotonergic proﬁ  le sometimes improve mood and global 
Psychological cognitive treatment, focusing on perfectionism, 
rigidity, scrupulousness, and intolerance of failure, is the main therapeutic approach. Repressed aggression, guilt, and dependency needs should be addressed using a psychodynamic approach.
Other personality disorders (not included 
in DSM-IV)
Passive–aggressive (negativistic) personality disorder
Resistance to demands for adequate social and occupational

in DSM-IV)
Resistance to demands for adequate social and occupational 
performance and negativistic attitude are considered to be central features of passive–aggressive personality disorder. A pervasive pat-tern of argumentativeness, oppositional behaviour, and defeatist 
attitudes are typical, and are thought to be a covert manifestation of underlying aggression, which is expressed passively and indirect-
ly. Passive–aggressive personalities have interpersonal and cognitive dysfunction and severe impairment in terms of self-image, global mental health, and ability to function at work and in intimate rela-tionships.
(56)
Passive–aggressive personality disorder was ofﬁ  cially included in

(56)
Passive–aggressive personality disorder was ofﬁ  cially included in 
DSM-I as the passive–aggressive personality ‘trait disturbance’ depicted as an immature reaction to military stress by helpless, passive, and obstructive resistant behaviour. However, passive–aggressive disorder was not included in DSM-IV because of the many unsolved problems related to its concept in previous classiﬁ  -
cations. Instead, it is placed in Appendix B of DSM-IV where it is alternatively called negativistic personality disorder. Research criteria are proposed which are expected to be empirically evaluated and to determine the validity and reliability of this diagnosis 
(Table 4.12.3.15).
There has been much debate as to whether passive aggression 
constitutes a personality disorder, a defence mechanism, or a speciﬁ  c 
maladaptive personality trait (coping style).
(57) Surprisingly, empiri-

cal literature on the subject is scarce, although passive–aggr essive behaviour has been widely recognized by clinicians. An
overlap with other personalities has been shown, and it has never been included as a separate category in the International 
Classiﬁ  cation of Diseases . The passive–aggressive dimension, as 
assessed by self-reports, is always high in depressed patients and is state-dependent.
(58) Perhaps it would be best to conceptualize 
passive aggression as a continuum: a passive–aggressive defence mechanism may be normal in some situations, it could be a trait of many personality disorders, and when pronounced and long-lasting it should be designated as passive–aggressive personality disorder.

The population prevalence ranges from 0.9 to 3 per cent, but in those cases in which a secondary co-occurring diagnosis was assigned, the secondary frequency of passive–aggressive personality disorder was about 10 per cent.
(59) Some studies found a higher 
prevalence in women and others in men.
The cause of the disorder is multidimensional, comprising biologi-cal, psychoanalytical, behavioural, interpersonal, and social learning perspectives.
Ambivalence is considered to be a core conﬂ  ict of passive–
aggressive personalities, which originates from ﬁ  xation to the 
biting or sucking stages of the oral phase of psychosexual develop-ment. Some authors consider masochism to be another precursor of the passive–aggressive personality.
According to the behavioural model, passive–aggressive

According to the behavioural model, passive–aggressive 
behaviour is the expression of anger in maladaptive verbal and non-verbal ways that do not lead to rewarding problem-solving Failure to learn appropriate assertive behaviour would be the main aetiological factor.
(60)
The primary social factor influencing the development of 
passive–aggressive patterns would be contradictory parental attitudes in childhood which, being conﬂ  icting and incompatible, 
prevent the child from expressing his feelings directly and thus urge him to develop passive resistance.Table 4.12.3.15 DSM-IV research criteria for passive–aggressive 
A. A pervasive pattern of negativistic attitude and passive resistance to 
demands for adequate performance, beginning by early adulthood and present in variety of contexts, as indicated by four (or more) of the following
1 Passively resists fulﬁ  lling routine social and occupational tasks

2 Complains of being misunderstood and unappreciated by others3 Is sullen and argumentative
4 Unreasonably criticizes and scorns authority
5  Expresses envy and resentment toward those apparently more 
fortunate
6 Voices exaggerated and persistent complaints of personal misfortune7 Alternates between hostile deﬁ  ance and contrition
B. Does not occur exclusively during major depressive episodes and is not 
better accounted for by dysthymic disorder

877
Passive–aggressive personalities seek novel and stimulating 
situations in impulsive ways, while remaining unpredictable.(61)
Procrastination and inefﬁ  ciency are behaviours used to avoid 
responsibility, which they show by stubborn resistance to the fulﬁ  l-
ment of expectations and claiming forgetfulness.
Passive–aggressive individuals easily become irritable and, gloomy 
and they are resentful and discontent with life. Accumulated anger may be expressed by verbal acting-out, after which passive–aggressive individuals feel guilty and gloomy. Since they have difficulties in expressing emotions directly, they are prone to diffuse somatic complaints, hypochondriasis, and psychosomatic disorders.
Interpersonal ambivalence is a core feature of passive–aggressive 
personality disorder. Negativism is particularly expressed towards 
authorities, with whom they are never satisﬁ  ed and whom they

authorities, with whom they are never satisﬁ  ed and whom they 
criticize constantly. The argumentative self-detrimental behaviour of passive–aggressive personalities is often experienced by others as punitive and manipulative. Negative verbal comments, which are often caustic, and irritable and moody patterns of communication are typical.
Passive–aggressive individuals are cynical, sceptical, hypercritical, 
and mistrustful. Disillusioned with life, discouraged, discontented with themselves and with others, they are also pessimistic about the future. They persistently complain and blame others for their own bad luck, feeling themselves to be misunderstood martyrs and victims of destiny.

Passive–aggressive personality disorder is frequently comorbid with major depression, dysthymic disorder, anxiety, panic disorder, and hypochondriasis. Patients with depressive disorders are more aware of their feelings of inferiority and more likely to feel guilty, and their depressed mood is continuous rather than erratically hostile and moody, as in passive–aggressive personality.
Comorbidity with many personality disorders (histrionic, 
borderline, obsessive–compulsive, dependent, narcissistic) is also frequently observed. People with these personality disorders may use passive aggression as a defence mechanism. Suicide attempts are not as frequent as in histrionic and borderline personality disorders, and features of passive–aggressive personality are less dramatic, affective, openly aggressive, and severe.
There are insufﬁ  cient data on the course and prognosis of passive–

aggressive personality disorder. When passive–aggressive people are unable to control their anger, they may experience anxiety, panic states, depressive episodes, chronic depression, and psychosomatic disorders. They are prone to alcohol abuse, and their careers are erratic and stunted despite their abilities (frequent changes of jobs are common). Suicide attempts may complicate this disorder.
(i) Pharmacotherapy
Target symptoms, such as depression, anxiety, and somatic com-plaints, should be treated. Benzodiazepines may be warranted and helpful in the initial period of psychotherapy. The side effects of medication are often the reason for complaints about their psychiatrist’s inefﬁ  ciency. Non-compliance is frequent, reﬂ  ecting 
resistance to the therapist. Abuse of medicaments should be controlled and considered seriously.(ii) Psychotherapy

Psychotherapy is the treatment of choice. Various modes are used, including supportive, psychodynamic, behavioural assertiveness training, and the paradoxical approach in group or individual settings. The goal of treatment should be to help the patient escape from the vicious circle of self-defeating behaviour and develop a mature way of expressing anger and other feelings.
Self-defeating (masochistic) personality disorder
Individuals with masochistic personality disorder persistently seek humiliation and failure, and submit to the will of others.
The term masochism was introduced to psychiatry by Krafft-

Ebing in 1882. It is derived from a character in a novel by the German author Leopold von Sacher-Masoch, a man who endured torture, scorn, and humiliation from a woman. Later, Freud conceptualized masochism as the result of aggressive instinct directed towards the self instead of an external object. Reich
(62)
described the masochistic character as a person who suffered deep frustrations in early developmental stages and needed to express this frustration through suffering inﬂ  icted by the love ‘objects’ . 
Thus deﬁ  ance is always present in the masochistic search for love. 
According to Horney,
(63) helplessness and victimization may be a

(63) helplessness and victimization may be a 
masochistic way of expressing hostility by making others feel shameful. Masochistic suffering may also be used to avoid reproach and responsibility and as a way of restoring a sign of personal value.
(a) Clinical picture
People with self-defeating personality disorder avoid pleasurable experiences and undermine their achievements. They neglecttheir appearance and live below their means. They accept and endure humiliation, expecting that others will sympathize with them. In this way, they fulﬁ  l their expectation that submission
will bring love and care. They prefer to relate to people who abuse them and consider those who consistently treat them well to be boring.
These people fail to accomplish tasks of which they are capable

These people fail to accomplish tasks of which they are capable 
and adopt an inferior role. When making appropriate demands, they feel that they are taking advantage of others and adopt an apologetic manner. For them, success is inversely related to inner security. Successful relationships do not make them feel conﬁ  dent, 
but increase their fears. They tend to believe that all experiences 
involve future frustration and pain. They may respond to positive 
personal events with depression and behaviour that negates their accomplishments. They look for people who will respond to their behaviour with disdain, rejection, or cruelty.
People with self-defeating personality disorder do not defend 
themselves against expressions of disgust and resentment directed towards them and rarely accuse or reproach others. They do not feel conﬁ  dent and are not assertive. They fear that optimism may 
lead to greater problems.
They are not worried by these attitudes. Rather, masochists

They are not worried by these attitudes. Rather, masochists 
believe that by exaggerating their weaknesses and inefﬁ  ciency they 
will protect themselves from aggression by others. They feel protected when someone needs something from them, and many non-assertive masochists engage in self-sacriﬁ  ce for their own 
protective feelings rather than for the welfare of others. What seems to be a comprehensive and self-sacriﬁ  cing attitude reﬂ  ects a lack 
of conﬁ  dence and empathy.4.12.3 specific types of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 878
The mood of these individuals is usually dysphoric, ﬂ  uctuating 
between anxiety and sadness.
Since masochistic personality disorder is not included in DSM-IV , little research has been done on comorbidity or on the validity or speciﬁ  city of this diagnosis.
Self-defeating attitudes, low self-esteem, and depression may be 
found in individuals with dependent, borderline, and depressive personality disorders. Some of the characteristics are also found in avoidant personality disorder.
Masochists are prone to mood disorder and dysthymia. Anxiety 
disorders are frequent. Their fears of abandonment are a persistent source of anxiety. Hypochondriasis and somatization are also common, sometimes as a way of obtaining attention.
(c) Treatment

Antidepressants and anxiolytics may be useful to alleviate a dysphoric state. Psychological treatment should take into account that masochistic patients sometimes induce an aggressive countertrans-ference as a response to their own wish to be hurt. The therapist should gradually clarify the behaviours, which provoke hostile responses and seek to reward adaptive interpersonal behaviours. Training in assertiveness and social skills is sometimes helpful.
Sadistic personality disorder

Sadistic personality disorder is a controversial category, which is not included in either DSM-IV or ICD-10. Some authors, especial-ly those working with perpetrators of abuse, support its inclusion in the diagnostic nomenclature, believing that it is a valid clinical entity, which deserves special treatment. Sadism as a term describ-ing desire to inﬂ  ict pain upon the sexual object was originally 
used by Krafft-Ebing.
(64) Kernberg(32) connects two dispositions 
(sadistic and masochistic) into a sadomasochistic character, which includes ‘help-rejecting complainers’ and often has underlying bor-derline personality organization.
Subjects with sadistic personality disorder often had a history of signiﬁ  cant childhood loss and physical, emotional, or sexual abuse 
during childhood.
(65) Despite their signiﬁ  cant psychopathology,

(65) Despite their signiﬁ  cant psychopathology, 
sadistic individuals are surprisingly highly functioning, with steady employment and intense long-lasting relationships.
Sadistic individuals demonstrate a long-standing maladaptive pattern of cruel, demeaning, and aggressive behaviour towards others in order to cause suffering and pain and to establish domi-nance and control. Sadistic persons are fascinated by violence, weapons, injuries, and torture, and are most frequently encoun-tered in forensic settings among child and partner abusers.

The major distinction for the diagnosis of sadistic personality disorder is from antisocial personality disorder. Sadistic persons may simply represent an aggressive (antagonistic) subtype of psychopathy. Intimidation and sadistic control of others, as well as a fascination with weapons, martial arts, and torture, may be mani-fested by both antisocial and sadistic individuals. Moreover, both disorders may display ‘malignant narcissism’ ,
(37) with an admixture 
of narcissistic, antisocial, sadistic, and paranoid features.(d) Epidemiology
Existing data(66) suggest that sadistic personality disorder is 
relatively uncommon, although it may have a higher prevalence in speciﬁ  c forensic populations. Several studies found a high overlap 
with narcissistic, paranoid, and antisocial personality disorders, 
which raised the possibility that sadistic personality disorder may 
not be a distinct entity.
(e) Course
No data are available on the course of this disorder.

(e) Course
Sadistic individuals seldom seek treatment, and are usually encoun-tered in forensic settings. No treatment has been successful for this disorder. Since the aetiology is probably multifactorial, there should be multiple approaches to treatment. The primary aim of treatment is control of cruelty and malignant aggression. As with antisocial personalities, selective serotonin reuptake inhibitors and lithium may be beneﬁ  cial in regulating the serotonergic function 
that probably underlies the aggressive action, and carbamazepine and clonazepam may act to regulate ictal aggressive outbursts.
Psychotherapy is usually difﬁ  cult because these individuals lack

Psychotherapy is usually difﬁ  cult because these individuals lack 
any desire to change and because there may be serious counter-transference problems for the therapists. Small groups may be helpful because there is a dissolution of transference and peer confrontation is accepted more easily.
Depressive personality disorder
This personality disorder is not included in ICD-10 or DSM-IV , although it is considered as a subject for further study in the latter. However, the concept of depressive personality was well recognized in previous decades (e.g. by Kraepelin and Schneider). Depressive personality was seen as a pattern of brooding, pessimism, and low self-conﬁ  dence,
(2) and as a tendency to physical lassitude and 
suffering. Phenomenological accounts(67) emphasize dependency,

suffering. Phenomenological accounts(67) emphasize dependency, 
orderliness, and adherence to social conventions. The psychoana-lytic concept of masochism
(47) overlaps to some extent with the 
classical depressive personality. More recently, Akiskal(68) has dis-
cussed the depressive personality as part of a spectrum of affective disorders, reviving Kretschmer’s ideas
(10) on the role of tempera-
ment as the base from where psychiatric disorders develop.
Psychological and biological factors have been suggested as causes of depressive personality disorder. Early losses, inadequate atten-tion from parents, and a punitive superego have been postulated by psychoanalytic authors. Others have suggested that a depressive temperament is genetically related to affective disorder.

People with depressive personality disorder are submissive, quiet, introverted, and unassertive. Their cognitive style is marked by pessimism, dejection, and self-reproach. They appear gloomy, joyless, cheerless, and unhappy. They are serious and lack a sense of humour. They do not believe that they deserve to be happy. They have a negative view of the past and present and do not expect things to improve. They anticipate failure and dwell on their nega-tive perspective of life. They have a low tolerance to shortcomings and failures, which are seen as conﬁ  rming their own pessimistic 
assumptions. They are prone to guilt and judge themselves severely.

879
Their self-esteem is low and they feel inadequate. They focus on the 
failings of others and are critical of themselves.
No data are available on the frequency of this disorder in the  population.
Some clinicians doubt whether a distinction can be madebetween depressive personality disorder and dysthymic disorder. The diagnosis of depressive personality disorder emphasizescognitive and behavioural aspects rather than the depressedmood. Also, dysthymia, although chronic, has a fluctuatingcourse.
Dysthymic patents generally experience their symptoms as 
egodystonic, while people with depressive personality disorder think that they have a realistic view of their situation. People with depressive personality disorder may meet the criteria for depen-dent personality disorder and self-defeating personality disorder, and it is difﬁ  cult to distinguish between these disorders.
(e) Course

(e) Course
Patients with depressive personality disorder have depressive 
episodes and dysthymia more frequently than other individuals, and may have difﬁ  culties in adapting to stressful or uncertain 
Antidepressants may be useful when the person is at higher risk for developing a depressive episode. Psychological treatment may be helpful, since these people have a good capacity for introspec-tion and reality testing. Cognitive approaches can help patients to understand their negative views and derogatory attitudes. These patients usually establish a good therapeutic relationship with the clinician.
Personality changes
Enduring personality changes after traumatic 
ICD-10 has two categories for personality changes: those occurring 
after catastrophic situations, and those starting after psychiatric ill-ness. Either diagnosis should be made only when there is evidence of a deﬁ  nite personality change, including cognition, behaviour,

and interpersonal relationships. The changes must not be a mani-festation of a current mental disorder or the residue of a previous mental disorder. It must not be an exacerbation of a pre-existing personality disorder.
The aetiology  of the personality change presumably relates to 
the extreme existential experience of the catastrophic situation or the psychiatric illness.
Examples of catastrophic experiences include life in concentra-
tion camps, experiences of disaster, and prolonged exposure to other life-threatening situations. Personality changes following 
short-term exposure to life-threatening situations, such as a car 
accident, should not be included in this group, since such changes probably depend on a previous psychological vulnerability. In ICD-10, the symptoms of personality change after catastrophic experiences include hostility and mistrust of the environment, social withdrawal, feelings of emptiness or hopelessness, estrange-

ment, and alertness or feeling on the edge.
When the personality change follows a mental disorder, the cause 
is related to the stressful experience and the perceived damage to the patient’s self-image arising from the disease. Other people’s attitudes towards the illness, the subjective emotional experience, and previous psychological adjustment are also important. Features of the personality change after mental disorders include feelings of being stigmatized and consequent withdrawal, passivity, and loss of interests, dependence, excessive demandingness and complaining, and dysphoric–labile mood.
Personality change due to a general medical 
condition (JLC)
This category, which is included in both ICD-10 and DSM-IV , 
describes syndromes affecting global features of behaviour, cogni-tion, and emotions, and secondary to the physiological effects of general medical diseases.
The essential feature is a change in personality after a general

The essential feature is a change in personality after a general 
medical disease. In childhood before a stable pattern of personality has been established, a marked deviation from normal develop-ment suggests the diagnosis.
A central feature is loss of control over the expression of
emotions and impulses. Affect is commonly labile and shallow, although persistent mild euphoria or apathy may be present,especially when the frontal lobes are affected. The elevatedmood of these patients is hollow and silly, unlike that of hypoma-nia. Patients may appear childish, expansive, and disinhibited, but 
they may admit to not feeling happy. Others are indifferent and 
apathetic.
Exaggerated expressions of rage and aggression are usually 
present, often out of proportion to any stressor. Loss of impulse control is also shown in social and sexual disinhibition, inappro-priate jokes, and overeating.

In most cases this disorder is associated with structural damage to the brain. Head trauma, cerebral neoplasms, vascular accidents, multiple sclerosis, Huntington’s disease, and complex partialepilepsy may all cause personality change, especially whenaffecting frontal and temporal lobes. Systemic diseases involving the central nervous system, including endocrine disorders, AIDS, lupus erythematosus and chronic metal poisoning, may have the same effect.
Patients with this disorder generally have a clear sensorium 
but may be inattentive and have some mild cognitive dysfunction. They do not show intellectual deterioration.

In dementia, personality change is accompanied by intellectual deterioration. However, personality change may predate the demen-tia. Distinction from schizophrenia and other personality disor-ders is based on the clinical history and the presence of a general medical disease capable of causing personality change.
If possible, treatment is directed to the causative condition. Pharmacological treatment of speciﬁ  c symptoms may be useful 
when depression or inappropriate anger is present.4.12.3 specific types of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 880
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New Y ork.4.12.4 Epidemiology of 
personality disorders
tbegun to be scientiﬁ  cally investigated. This development has taken 
place because a number of standardized instruments to assess personality and PD in an empirical fashion have been developed, in parallel with the reﬁ  nement of a valid and reliable diagnostic 
system based on a categorical approach.
The need for the epidemiological investigation of PDs seems jus-
tiﬁ ed for several reasons.
1 As seen in recent epidemiological surveys, PDs are frequent

1 As seen in recent epidemiological surveys, PDs are frequent 
and have been found in different countries and sociocultural settings.
2 PDs can seriously impair the life of the affected individual and 
can be highly disruptive to societies, communities, and families.
3 Personality status is often a major predictive variable in deter-
mining the outcome of Axis I mental disorders and the response to treatment.
In this chapter, we review the epidemiological literature on PDs 
up to October 2007, focusing on studies carried out since the devel-opment of the DSM-III. First, community prevalence studies of PDs are reviewed. We then look at the prevalence of individual PDs in the community. Finally, we consider the prevalence of PDs in clinical populations, and in special settings (e.g. primary care, prisons, etc.).
Community epidemiological studies of

Community epidemiological studies of 
unspeciﬁ  ed personality disorders
Until the development of the DSM-III diagnostic criteria for 
PDs and the subsequent availability of standardized assessment instruments, epidemiological studies aimed at assessing the pre-valence rate of PDs were hampered by severe methodological 
limitations, including differences in sampling methods and in diag-
nostic criteria, the known unreliability of PD diagnoses based on clinical judgement, and the lack of standardized assessment methods. Since 1980, twelve main studies with at least 200 subjects sampled have ascertained the prevalence rate of PDs in different community samples using assessment instruments speciﬁ  c for PD; they are 
shown in Table 4.12.4.1.
In these studies, the sample sizes ranged between 200 and 2053 
subjects, with an average sample of 565.4; all surveyed individuals were evaluated by means of a speciﬁ  c PD assessment instrument,

subjects, with an average sample of 565.4; all surveyed individuals were evaluated by means of a speciﬁ  c PD assessment instrument, 
mainly a structured interview. While most studies were carried out 
in one stage, Lenzenweger et al.
(6) ﬁ rst screened a large sample of 
university students with a self-administered Axis II inventory, and 
then interviewed a subgroup of 258 subjects using the International 
Personality Disorder Examination. The median prevalence rate of 
any PDs in these eight studies is 12.5 per cent.
Two large community studies(13,14)  carried out in the USA were 
not included in Table 4.12.4.1 since PD prevalence rates were based 4.12.4 epidemiology of personality disorders

SECTION 4  clinical syndromes of adult psychiatry 882
on screening questions(13) and on a newly developed fully
diagnostic structured interview carried out by lay interviewers rather than clinicians, which lacked any accompanying validity data.
(14)
In the surveys considered here, the rate of PDs decreases in older 
age groups; although the sex ratio is different for speciﬁ  c types of 
PD (e.g. more schizoid, narcissistic, and antisocial PDs among males, more dependent, avoidant, and histrionic PDs among females), the overall rates of PD are about equal for both sexes. Finally, prevalence rates are generally higher in urban populations and lower socio-economic groups.
speciﬁ  ed personality disorders
Table 4.12.4.2 lists the median prevalence rates for speciﬁ  ed PDs 
based on studies that surveyed different types of randomly selected community samples. We will comment on some of the ﬁ  ndings.

based on studies that surveyed different types of randomly selected community samples. We will comment on some of the ﬁ  ndings. 
The ﬁ  rst column shows the number of studies on which the 
median prevalence rate is based.
The median prevalence rate of paranoid PD is 1.6 per cent. In the study by Baron,
(15) paranoid PD was remarkably more common 
among relatives of schizophrenic probands (7.3 per cent) than among relatives of control probands (2.7 per cent).Schizoid personality disorder
There have been 13 studies evaluating the prevalence of schizoid PD in the community, with a median prevalence rate of 0.8 per cent. Baron
(15) reported a rate of 1.6 per cent of schizoid PD among 
relatives of schizophrenic probands, but no cases among relatives of control probands.Table 4.12.4.1 Prevalence rates of personality disorders in epidemiological surveys
Reference Country Sample

Reference Country Sample 
sizeSample features Diagnostic 
CriteriaAssessment 
methodPD prevalence 
rate (%)
Black et al.(1)USA 247 Relatives of obsessive-compulsive and normal control 
probandsDSM-III-R SIPD 22.3a
Casey & Tyrer(2) UK 200 Urban and rural residents ICD-9 PAS 13.0
Coid et al.(3) UK 626 Urban and rural residents aged 16–74 and selected in a 
2 phase survey (weighted data)DSM-IV SCID-II 4.4
Crawford et al.(4) USA 644 Individuals re-interviewed from previous surveys, mean 
age 33.1 years (range 27.7–40.1)DSM-IV SCID-II 15.7
Klein et al.(5)USA 229 Relatives of normal controls DSM-III-R PDE 14.8
Lenzenweger et al.(6)USA 258 University students age 18–19 years (two-stage 
procedure)DSM-III-R IPDE 3.9b
Maier et al.(7) Germany 452 Normal controls, their partners, and relatives DSM-III-R SCID-II 10.0

Moldin et al.(8)USA 302 Normal controls, parents and their children DSM-III-R PDE 7.3
Reich et al.(9)USA 235 Urban residents DSM-III PDQ 11.1
Samuels et al.(10)USA 742 Individuals re-interviewed from previous survey, aged 
34–94 years (weighted data)DSM-IV IPDE 9.0
Torgersen et al.(11) Norway 2,053 Individual from National Register (weighted data) DSM-III-R SIPD 13.4
Zimmerman & Coryell(12) USA 797 Relatives of patients and normal controls DSM-III SIDP 14.3a
PAS, Personality Assessment Schedule, IPDE, International Personality Disorder Examination; PDE, Personality Disorder Examinati on; PDQ, Personality Diagnostic Questionnaire; SCID—II, 
Structured Clinical Interview for DSM-IV Axis II disorders; SIDP , Structured Interview for DSM-III-R Personality.
a Prevalence includes those with ‘mixed’ and ‘not otherwise speciﬁ  ed’ disorder.

b Prevalence was 6.7% ‘deﬁ  nite’, 11% ‘possible’, including ‘not otherwise speciﬁ  ed disorder’.
Table 4.12.4.2 Median prevalence rates of speciﬁ  ed personality 
disorders in epidemiological surveys
PD Category Number of studies ( N) Median prevalence rate ( %)
Paranoid 13 1.6
Schizoid 13 0.8Schizotypal 13 0.7Antisocial (dissocial) 24 1.5Borderline 15 1.6Histrionic 12 1.8Narcissistic 10 0.2Obsessive-compulsive 13 2.0Avoidant (anxious) 13 1.3Dependent 12 0.9Passive-aggressive 8 1.7

883
The median prevalence rate of schizotypal PD is 0.7 per cent. 
However, in the study by Baron(15) schizotypal PD was remark-
ably more common among relatives of schizophrenic probands(14.6 per cent) than among relatives of control probands (2.1 per cent). In a similar fashion, Asarnow et al.
(16) reported signiﬁ  cant-
ly higher rates of schizotypal personality disorders in relatives of probands with childhood onset of schizophrenia than in relatives of community controls (4.2 per cent vs. 0 per cent). These results provide additional support for the speciﬁ  c relationship between 
schizophrenia and schizotypal PD.
Antisocial (dissocial) personality disorder

Antisocial is the most studied PD. Its prevalence has been assessed in 24 epidemiological surveys, with a mean sample size of 2 943 subjects; nine studies used the Diagnostic Interview Schedule as assessment instrument. Antisocial PD seems to have a prevalence of around 1.5 per cent in the general population and to be substantially more frequent among males than females, with sex ratios ranging from 2:1 to 7:1. It is also more common among younger adults, those living in urban areas, and the lower socio-economic classes. People with a diagnosis of antisocial PD are also high users of medical services.
Borderline PD has been investigated in 15 studies. Swartz et al.(17)
carried out a study among 1 541 community subjects (between 19

carried out a study among 1 541 community subjects (between 19 
and 55 years of age) at the North Carolina site of the Epidemiologic Catchment Area (ECA) Program, using a diagnostic algorithm derived from the Diagnostic Interview Schedule ( DIS). They found 
a rate of 1.8 per cent for borderline PD; the disorder was signiﬁ  -
cantly more common among females, the widowed, and the unmarried. There was a trend towards an increase in the diagnosis in younger, non-white, urban, and poorer respondents. The highest rates were found in the 19 to 34 age range, with the rates declining with age. All borderline respondents had also a DIS DSM-III Axis I lifetime diagnosis.
Although some believe there is a preponderance of females 
with borderline PD, they do not always take into account that there is also a preponderance of females in the populations

with borderline PD, they do not always take into account that there is also a preponderance of females in the populations 
studied. There were two studies that did not ﬁ  nd a higher female 
prevalence.
(11,18)
Histrionic PD has a median prevalence rate of 1.8 per cent, rang-ing from 0 per cent
(3) to 3.2 per cent.(1) A study by Nestadt et 
al.(19) carried out at the Baltimore (Maryland) site of the 
Epidemiologic Catchment Area Program, ascertained the preva-lence of histrionic PD in the community. The authors found a 
prevalence of 2.1 per cent in the general population, with virtually identical rates in men and women. No signiﬁ  cant differences were 
found in terms of race and education, but the prevalence was sig-niﬁ cantly higher among separated and divorced persons. It should

found in terms of race and education, but the prevalence was sig-niﬁ cantly higher among separated and divorced persons. It should 
be noted that the study derived the diagnoses from instruments not originally intended to diagnose PDs; it might be possible that, in some cases, this study has identiﬁ  ed personality traits rather 
than ‘true’ PDs.Narcissistic personality disorder
No cases of narcissistic PD were found in ﬁ  ve studies. However, 
Reich et al.(9) and Lenzenweger et al.(6) found rates of 0.4 per cent 
and 1.2 per cent respectively, even higher rates were found by Klein et al .
(5) and Crawford et al .(4) who reported prevalence rates of 
3.9 and 2.2 per cent respectively.
Obsessive compulsive (anankastic) 
The median prevalence rate of obsessive compulsive PD, obtained

The median prevalence rate of obsessive compulsive PD, obtained 
from 13 studies, was found to be 2 per cent, the highest of all PDs. The rate of compulsive PD was especially high in a study in which the Personality Diagnostic Questionnaire was used (6.4 per cent).
(6)
However, lower rates were reported with structured interviews. A community study, carried out at the Epidemiologic Catchment Area Program Baltimore site, found a prevalence of 1.7 per cent.
(20)
Males had a rate about ﬁ  ve times higher than females. The disorder 
was also more frequent among white, highly educated, married, and employed subjects, and it was associated with anxiety disor-ders. However, the study derived the diagnosis from an interview originally not intended to diagnose PDs; this may mean that adaptive obsessive compulsive traits, rather than a ‘true’ PD, were identiﬁ  ed. In the study by Black et al.

(1) rates of obsessive compul-
sive PD were higher among relatives of probands with obsessive compulsive disorder compared to relatives of comparison probands (10.8 per cent vs. 7.9 per cent, respectively), however this difference did not reach statistical signiﬁ  cance.
Avoidant (anxious) personality disorder
A total of 13 studies have investigated the prevalence of avoidant PD 
in community samples, with a median prevalence rate of 1.3 per cent. In the study by Asarnow et al .
(16) avoidant PD occurred more 
frequently in relatives of schizophrenia probands compared to comparison control probands, also when controlling for schizoid or paranoid PD, and the authors suggest that avoidant PD might be a separate schizophrenia spectrum disorder, and not merely a sub-clinical form of schizoid or paranoid PD.
Dependent personality disorder
In 12 studies in which the frequency of dependent PD was assessed, the median prevalence rate was 0.9 per cent.
Passive-aggressive personality disorder

The median prevalence rate of passive-aggressive PD, obtained from 8 studies, was found to be quite high (1.8 per cent); interest-ingly, this type of PD has not been included either in DSM-IV or in ICD-10.
Epidemiological studies of 
personality disorders carried out in psychiatric settings
Table 4.12.4.3 lists the median prevalence rates for any PDs found 
in 61 studies carried out in inpatient and outpatient psychiatric samples and published between 1981 and October 2007. Only pro-spective studies that surveyed clinical samples (either inpatients or outpatients) of more than 100 subjects have been considered for 4.12.4 epidemiology of personality disorders

SECTION 4  clinical syndromes of adult psychiatry 884
this analysis. The second column shows the number of studies on 
which the median prevalence rate is based.
In these studies, subjects have been directly evaluated for the 
purpose of obtaining PD rates, by means of a standardized assess-ment instrument speciﬁ  c for PDs. Several other studies, which have 
evaluated only the prevalence of speciﬁ  ed PDs in clinical samples, 
are not shown here.
In general, the prevalence of PDs among psychiatric outpatients 
and inpatients is quite high, with a substantial number of studies (n= 29) showing a PD prevalence rate equal or higher than 50 per 
cent of the sample. However, it is difﬁ  cult to draw more deﬁ  nite 
conclusions from these studies, because of substantial differences in sampling, diagnostic criteria, timing of the assessment, assess-ment methods, availability of mental health services, prevalence of Axis disorders, and sociocultural factors.

There are, however, some consistencies across studies that 
deserve consideration. The most prevalent PD seems to be border-line, both in inpatient and in outpatient settings. The next most common PDs is histrionic, whereas schizoid PD is infrequently diagnosed. Borderline and histrionic PDs are also characterized by the lowest social functioning. They are especially common in inpatient settings, as their symptomatology often results in the patient being admitted to hospital due to their suicidal behaviour, substance abuse, and cognitive-perceptual abnormalities. In outpatient settings, dependent, and passive-aggressive PD are also common.
Especially in inpatient settings, many people who meet the 
criteria for one PD also meet the criteria for other PDs 
(21–23) . The 
highest comorbidity rate appears to occur with borderline PD, with the frequent coexistence of borderline and histrionic PDs, antisocial, schizotypal, and dependent PDs.

With regard to comorbidity between PDs and Axis I disorders, 
the most common and best-studied patterns are between sub-stance abuse and PDs, affective disorders and PDs, and anxiety disorders and PDs (particularly borderline, antisocial, avoidant, 
and dependent PDs). Other clinically signiﬁ  cant associations 
have been found between PDs and eating disorders: obsessive-compulsive, avoidant, and dependent PDs are most commonly associated with anorexia nervosa whereas borderline, avoidant, dependent, and paranoid PDs are the most common among individuals with bulimia.
(24) High rates of PD (especially
borderline and antisocial PDs) have also been detected in patients with selected medical conditions, such as HIV-positive patients.
(25,26)Some studies have assessed the treated prevalence of PD using

(25,26)Some studies have assessed the treated prevalence of PD using 
administrative data (e.g. discharge ﬁ  gures, psychiatric case register 
data, etc.). In the United States, using data from the 1993 National Hospital Discharge Survey, Olfson and Mechanic
(27) found that 
almost 12 per cent of patients discharged from public general hospitals had a diagnosis of PD, compared with 11 per cent of patients from non-proﬁ  t hospitals and 5 per cent of patients from 
proprietary general hospitals.
Some investigations, which compared the hospital admission 
rates for PD over time, allow us to assess the impact of diagnostic changes. In Denmark, sex- and age-standardized rates of ﬁ  rst-
admitted borderline patients signiﬁ  cantly increased during the 
16-year interval between 1970 and 1985, and this might be explained in terms of a change in diagnostic habits.
(28) In the

(28) In the 
United States, comparing the diagnoses given to inpatients in a large university-afﬁ  liated mental hospital in the last 5 years of the 
DSM-II era ( n= 5143) with those given in the ﬁ  rst 5 years of the 
DSM-III era ( n= 5771), a marked increase (from 19 per cent to 
49 per cent) was found in the diagnosis of PD, together with a decrease in the diagnosis of schizophrenia and a corresponding increase in the diagnosis of affective disorders.
(29)
The epidemiological ﬁ  ndings in treated samples are especially 
important if we bear in mind that the presence of a PD among those suffering from other mental disorders can be a major predic-tor of the natural history and treatment outcome. Therefore, an important clinical implication of these ﬁ  ndings is that patients in

treatment because of severe Axis I disorders must be carefully assessed with an assessment instrument speciﬁ  c for PDs, because of 
the high likelihood of diagnosing a PD and the subsequent need to adjust their treatment accordingly.
Epidemiological studies of personality 
disorders carried out in other settings
A few epidemiological studies on PDs have been carried out among 
patients attending primary healthcare settings; in these studies between 5 and 8 per cent of patients have been identiﬁ  ed as 
having a primary diagnosis of PD.
(21) When the assessment is made 
independent of the primary diagnosis, however, the average prev-alence rate can rise several-fold because of state effects. In a con-secutive sample of primary care attenders , a PD was diagnosed in 
24 per cent of the sample (N =303) and was associated with the 
presence of common mental disorders and unplanned surgery attendance, indicating that PDs may represent a signiﬁ  cant source 
of burden in primary care.
(30)

(30)
In other institutional settings, such as prisons, several studies 
have found very high rates of PDs. In the United Kingdom, two large-scale studies have been completed; in the ﬁ  rst, carried out 
among 750 prisoners representing a 9 per cent cross-sectional sample of the entire male unconvicted population, a PD was diagnosed in 11 per cent of the sample.
(31) In the second study, 
a representative sample of the entire prison population of England and Wales was evaluated; a sub-sample was assessed with the SCID-II administered by a clinician.
(32) The prevalence rates
for any PD were 78 per cent for male remand prisoners, 64 percent for male sentenced prisoners, and 50 per cent for female pris-oners. In a large meta-analysis by Fazel & Danesh 
(33) of 28 studies,Table 4.12.4.3 Median prevalence rates of PDs among psychiatric

(33) of 28 studies,Table 4.12.4.3 Median prevalence rates of PDs among psychiatric 
patients in prospective studies including more than 100 subjects
Diagnostic category Number of 
studies ( N)Median 
sample ( N)Median 
prevalence 
rates ( %)
Alcohol and substance abuse 15 250 57.0
Affective disorder 19 200 49.2Anxiety disorders 7 200 40.4Any Axis disorder 20 131 51.0

885
including a total of 13 844 prisoners, antisocial PD was diagnosed 
in 47 per cent of subjects. High rates of borderline and antisocial PDs have also been found in a sample ( n= 805) of women felons 
entering prison in a North American State.
(34)
Up to 30 years ago, the epidemiology of PDs had not received the same amount of attention as that of many other psychiatric disorders. Since then the situation has changed, and we now have data on the prevalence of PD in the community and in psychiatric facilities. Community data come primarily from 12 studies, with a total sample of 6 785 subjects from four countries (Germany, Norway, the United Kingdom, the United States). There are excellent national and cross-national epidemiological data on antisocial personality disorder based on the same diagnostic methods. There are almost no data on other PDs from countries other than the United States, the United Kingdom, Germany and Norway.

One important methodological problem is that some PDs have a 
very low prevalence rate. Consequently, epidemiological surveys carried out among the general population may require very large samples in order to identify a sufﬁ  cient number of cases to study 
demographic correlates and the association of PD with other psy-chiatric disorders. Future studies should try to address this prob-
lem and provide us with more deﬁ  nite epidemiological data. These 
data will also be invaluable in showing the validity of currentclassiﬁ  cations and in better delineating the boundaries between 
different PDs.
The complete bibliography of studies included in tables 4.12.4.2–4.12.4.3 can 
be asked from the authors at the e-mail address: f.guzzetta@gmail.com.
T orgersen S. (2005). Epidemiology. In The American Psychiatric Publishing 
Textbook of Personality Disorders (eds. Oldham J.M., Skodol, A.E., 
Bender, D.S.), pp. 129–41. The American Psychiatric Publishing.

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SECTION 4  clinical syndromes of adult psychiatry 886
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4.12.5 Neuropsychological

4.12.5 Neuropsychological 
templates for abnormal personalities: from genes to biodevelopmental pathways
The scaffolding of personality
Research on human personality has converged upon a ‘consensual 
pathway’ indicating that a small number of dimensions can provide the framework for describing the rich variety of human temperaments. These high-level temperamental traits are factori-ally derived from psychometric measures of individual variation in behaviour, feeling, and thinking,
(1,2) and it is assumed that they 
may reﬂ  ect the operation of brain systems that are probably multi-
faceted and multipurpose.(3–5) This global outline of the structure

faceted and multipurpose.(3–5) This global outline of the structure 
of personality depends on the notion that genetic and develop-mental dispositions combine with critical nurturing and social conditioning events to form the tapestry of human uniqueness within temperamental clusters. In other words, personality types are expressed through relatively clear-cut and stable phenotypic traits that are accessible to objective measurement at behavioural, emotional, and cognitive levels. These depend, in turn, upon the speciﬁ  c and early organization of particular neurocognitive and 
neuroendocrine templates.
A handful of ‘superfactors’ (broad traits or dimensions) appar-
ently capture the essential components of the mosaic of terms and traits used to describe normal personality. These dimensions are neuroticism ,extraversion ,agreeableness/friendliness ,conscientious-

ness, and intellectual openness . Neuroticism and extraversion always 
appear as main stars in these factorial solutions  whereas the remain-
ing three superfactors—conscientiousness (reliability/persistence), friendliness (as opposed to aggressiveness/hostility) and intellec-tual curiosity (openness/creativity)—have less regularity on such high-order taxonomies. A ﬁ  ve-dimensional structure is advocated 
by many researchers though dissent is still strong regarding the nature and scope of these superfactors that would deﬁ  ne the ‘core’ 
of human temperament.
(6)Biological rooting of personality types

Searching for biological substrates of personality dimensions would reinforce their validity as useful constructs but this endeav-our was largely neglected by psychometricians devoted to purely descriptive studies and by clinical researchers as well. Some pioneers, like Hans Eysenck at the Institute of Psychiatry, London, tried to root behavioural trait variations within neurobiological concepts
(1) following a venerable tradition, which can be traced 
back as far as Pavlov. These early proposals were rather rudimen-tary though they served as drivers of subsequent models which focused more tightly on certain brain subsystems as possible sites for the factors underlying normal and abnormal temperaments.
(3–5,7–9) Jeffrey Gray, Robert Cloninger, and Larry

(3–5,7–9) Jeffrey Gray, Robert Cloninger, and Larry 
Siever’s ideas were among the more fruitful in an area which has grown steadily and is now an lively field of personality research.
(9–11) Progress in basic neuroscience has made it possible 
to relate a variety of biological measures to paper and pencil or neurocognitive tests distinguishing normal and anomalous tem-peraments. Biological screening has also increasingly been applied to patients with personality disorders, using the clinical clusters as deﬁ  ned by Diagnostic Systems. Besides these attempts to build 
psychobiological proﬁ  les of normal and abnormal temperaments, 
converging evidence is used to advocate that categorical and dimensional models for diagnosing personality disorders should be integrated.
(12)
T o give a broad overview of an area that may be crucial to illumi-
nate the genesis of personality disorders, I shall discuss the studies that, during the last decade, have tried to ﬁ  nd genetic traces for

nate the genesis of personality disorders, I shall discuss the studies that, during the last decade, have tried to ﬁ  nd genetic traces for 
personality traits that are both behaviourally consistent and biologically well rooted. Previous work using classical (familial or twin) methods had found substantial heritability estimates for several personality traits.
(13) It was thus unsurprising that genetic

(13) It was thus unsurprising that genetic 
tracking methods impulsed research aimed at showing that temperamental traits contribute to personality scaffolding via neuroendocrine targets specified by particular genes. I’ll be discussing the outcome of some of these efforts and I’ll explore afterwards how other basic temperamental traits, rooted within biodevelopmental processes, do mediate enduring neurocognitive organization resulting in long-lasting behavioural styles. Finally I’ll outline new avenues for the neuropsychology of personality. My approach is deliberately selective, discussing relevant evidence rather than performing a systematic assessment of the ﬁ  eld. For 
reasons of convenience and possible clinical relevance, I have selected some of the traits heralding sound biological foundations, although they are not necessarily prominent in the state-of-the-art 
dimensional ‘ solutions ’ for normal and abnormal temperaments.
The genetic saga for novelty-seeking

In 1996 two independent teams reported(14,15)  that a particular 
chromosomal ‘locus’ was associated with a well-established trait of human temperament—the hunger for novelty and excitement that lies behind sensation-seeking, risk taking, and impulsive behaviours.
(5,10) A polymorphism in the sequence of the gene 
expressing the D4 dopamine receptor (D4DR), located on the short arm of chromosome 11, explained 10 per cent of the genetic variance due to this trait. Individuals with the longer repeat allele at exon III of the D4DR  gene scored higher in novelty-seeking

887
behaviour (explorers, risk-seekers), whereas those with the shorter 
allele had lower scores (prudent, cautious). The ﬁ  rst of these 
studies(14) investigated a heterogeneous sample of young Israelis, 
and showed the association to be independent of ethnicity (Ashkenazim versus Sephardim), sex, or age. The second study, carried out in the United States,
(15) used a random sample of 
people who had initially been recruited in a search for chromo-somal regions possibly associated with sexual orientation; this sample mainly comprised white men, although some ethnic minorities were also included. The personality questionnaires were different but very popular in personality research: the Israelis were evaluated using Cloninger’s Tridimensional Personality Questionnaire ( TPQ ),
(16) which gives direct scores of novelty-
seeking, whereas the American study used the Revised NEO Personality Inventory
(17) which measures the ﬁ  ve superfactors

(17) which measures the ﬁ  ve superfactors 
mentioned above, from which scores for novelty-seeking were derived. The results of the two studies were highly concordant.
Despite the modest explanatory power of this reported associa-
tion, the link between temperamental variability for one trait and a chromosomal polymorphism was the ﬁ  rst hint for a direct rela-
tionship between a putative ‘genetic marker’ and a core dimension of normal personality. In this case, the potential genetic marker appeared promising because of the amount of basic and clinical research linking dopaminergic function with the regulation of stimulus-seeking and sensitivity to incentives. In theory, if similar degrees of explained variance were assignable to other sound gene markers associated to approach /exploring  phenotypes, a substantial

part of the heritability of the trait could be explained. Subsequent 
studies
(18,19)  failed to replicate these early ﬁ  ndings in a consistent 
way and the optimism receded. The heterogeneity of the samples and the subtleties of the genetics of complex traits were blamed for the disparate results, though the research saga was quite produc-tive: the links between dopamine receptor polymorphisms and novelty-seeking have been intensively searched and the race to ﬁ  nd 
other markers for the same trait was impressive.
Metanalyses suggest that there are subtle connections between 
dopamine receptor gene variants and approach /exploring  pro-
pensities as measured by personality questionnaires, though the strength of the contribution of every variant is small and hard to establish.
(19,20)  Moreover, parallel research has established sugges-

tive connections between gene variants regulating other molecular targets (i.e. tryptophan hydroxylase, dopamine transporter, dopamine-beta-hydroxylase, serotonin transporter, MAOA, COMT) that modulate risk-taking behaviours and impulsivity. A handful of genes, thus contribute to differential vulnerabilities for addictive behaviours, a congruent result at the extreme of stimulus-seeking tendencies. Although further and more reﬁ  ned 
research is required, these data seem to conﬁ  rm pioneer work, 
mostly with twins, which had consistently established that novelty-seeking behaviour was moderately heritable (40 to 50 per cent).
Genetics of fearfulness/neuroticism
The aforementioned American team that reported the ﬁ  rst associa-

tions between novelty-seeking and variants of D4DR gene informed that there was an association between the neuroticism trait and a chromosomal region linked to serotonin neurotransmission involved in modulating anxiety-related traits.
(21) The 5-hydroxy-
tryptamine transporter protein (5-HTT) that promotes the reuptake of serotonin into cell membranes is encoded by a gene 
(SLC6A4 ) located in the q11–q12 segment of chromosome 17. The 
region governing the transcriptional control of the protein shows a polymorphism that inﬂ  uences its expression and functioning. 
Individuals carrying the short variant of the polymorphism show a reduced efﬁ  ciency of serotonin reuptake compared with those

possessing the longer variant. The study measured these parame-ters in the lymphoblasts of two independent samples totalling more than 500 volunteers. Using two different personality questionnaires (NEO and Cattell’s 16PF Personality Inventory) and estimated scores on various dimensions of Cloninger’s TPQ, the evidence showed that subjects who carried the short variant in the 5-HTT gene polymorphism had higher neuroticism (NEO), anxiety (16PF), and harm-avoidance (TPQ) scores. The results were equally consistent across and within pedigrees. Across the three personality measures, the 5-HTTLPR contributed a modest 3 to 4 per cent of the total variance and 7 to 9 per cent of the genetic variance in anxiety-related traits. It was suggested that, if other genes contrib-uted similar dosage effects to anxiety traits, approximately 10 to 15 genes might be involved in the heritability of neuroticism.
The implication of the serotonin transporter in the potential

The implication of the serotonin transporter in the potential 
genetic predisposition towards emotionality traits agrees with many other results. Serotonergic neurotransmission is involved in multiple brain functions with little or no relationship with fear/anxiety regulation, but there is a large body of evidence linking it with the modulation of adaptive responses to serious conﬂ  ict 
and emotionally demanding situations.
(3) Moreover, many drugs 
currently used to treat anxious/depressive dysphorias and person-ality disorders depend on mending serotonergic function. Finally, several studies have shown that variants of the 5-HTTLPR predict differential response on anxious phenotypes: fear-driven amygdala activation
(22) and response to pharmacological challenges.(23)

Therefore, although the exact role of serotonergic systems in the modulation of emotionality is not fully understood, it is improbable that the neurohormonal adaptations that participate in individual responses to serious emotional conﬂ  icts would not include sero-
tonin modulation either through the cell transporter or through the extended family of serotonin receptors and their intracellular targets. Defensive adaptations require however the participation of other central neuromodulators: the CRH-ACTH regulatory cascade, γ-aminobutyric acid, neuropeptide Y, and substance P ,
(3)
are major contenders in this respect and they can be expected to 
contribute to the genetic mediation of neuroticism.
Polymorphisms in anxious humans versus QTL-genes 
for fearful rodents
Dozens of studies investigated whether the particular polymor-

phism in the 5-HTT gene contributes to the tendency for individu-als who score higher on neuroticism, in personality tests, to be at higher risk for ‘internalizing disorders’ (anxiety/depression) and personality disorders (anxiety/affective clusters). The global out-come of that research has been unreliable: though stringent meta-nalyses conﬁ  rmed the original association with a modest relevance 
at explaining the trait variance,
(23) subsequent results in large 
samples of siblings and singletons have been negative.(24) There are 
other lines of evidence, however, mainly from animal research, that support the claim of a possible genetic basis for fearfulness/emotionality. This evidence is derived from studies of the4.12.5 neuropsychological templates for abnormal personalities

SECTION 4  clinical syndromes of adult psychiatry 888
psychogenetics of emotional susceptibility searching for chromo-
some loci. In many biological and behavioural tests, comparisons of several reactive and non-reactive strains of mice and rats obtained through artiﬁ  cial selection (forced interbreedings) have 
narrowed the search for genetic loci thanks to increasingly power-ful methods of chromosomal mapping. In a pioneer work with progeny obtained by crossing two strains of mice selected for activ-ity and defecation in an open-ﬁ  eld test, three loci (QTLs) which 
explained most of the genetic variance in emotionality were found on chromosomes 1, 12, and 15 of the murine genome.
(25) These 
data were conﬁ  rmed and extended by measuring fear responses 
towards particular cues: the same segment of chromosome 1 was identiﬁ  ed as a relevant ‘locus’ for emotional susceptibility besides 
other murine chromosomal zones.
(9) The importance of the loci at

(9) The importance of the loci at 
chromosome 1 has been established in studies using heterogeneous and inbred stocks, combining techniques which have permitted to focus the suspicious segment to less than 1 cM and leading to the identiﬁ  cation of the ﬁ  rst gene linked to murine emotionality:
Rgs2, a regulator of G-protein functioning which is highly expressed in the brain.
(26) The complexities are nevertheless tre-
mendous because even a QTL like that contains several genes each contributing a very modest part of variation on the phenotype of interest.
(9,26)
Several research programmes were concurrently started to 
determine whether there is also concordance in the chromosomal marking of emotionality in strains of rats differing in fearfulness. The hypoemotional Roman high-avoider ( RHA ) versus the hypere-
motional Roman low-avoider ( RLA ) rat lines represented a partic-

ularly interesting assay because of the very large body of evidenceshowing their usefulness as animal models of ‘temperamental’ styles.
(27) Several plausible QTLs were detected but only those 
located on chromosome 5 and 15 predicted a wide array ofanxious/fearful behaviours including spontaneous and learned fears.
(28,29)  The QTL located at the middle of rat chromosome
5 looks particularly promising because this region is partiallysyntenic with the human 1p segment where QTLs for neuroticism and liabilities for anxious/depressive dysphorias have been detect-ed.
(9,30) The search for plausible genes is, then, much more focused 
now though they will explain, in all probability, very modestportions of the phenotypic trait variance.
(9)
Biodevelopmental mechanisms for 
afﬁ liative traits
Afﬁ liation (friendliness, sociability, gregariousness, empathy) is

(9)
Afﬁ liation (friendliness, sociability, gregariousness, empathy) is 
another core personality trait that can be measured consistently. Poor or distorted afﬁ  liative behaviour is the most predictive marker 
for a reliable diagnosis of personality disorder.
(7,31)  Deﬁ  cits or 
alterations in afﬁ  liative tendencies may show a variety of clinical 
manifestations: extreme aloofness and detachment, manipulative, non-empathic or exploitative attitudes, and even deﬁ  nite asocial or 
antisocial tendencies. These behavioural styles appear, in different degrees and combinations, in several clinical categories of abnor-mal temperament. They could reﬂ  ect alterations in the functioning 
of neuroendocrine systems specialized in mediating affective attachments, possibly including subsystems for social reward and social distress.
(31) In this respect, an impressive amount of evidence

(31) In this respect, an impressive amount of evidence 
has been gathered (mostly in animals but in humans as well) showing that prosocial behaviours, such as maternal nurturing, friendliness/gregariousness, playful/sexual behaviours, and even 
cooperativeness in economic interactions, share some neuro-chemical controls.
(31–33)
Central oxytocin and opioid systems are among the more 
relevant of these modulatory molecules, because several types of attachments (mother–infant bonds, young peer bonds, pair-mating bonds, in-group tendencies) are dramatically altered when the functions of oxytocinergic or opioid systems in the brain are modiﬁ  ed. Other centrally acting neuropeptides, such as prolactin 
and vasopressin, also contribute to particular types of species-speciﬁ  c social bonding. In addition, both the central regulatory

and vasopressin, also contribute to particular types of species-speciﬁ  c social bonding. In addition, both the central regulatory 
monoaminergic systems and the corticotrophin–adrenal cascades that mediate stress adaptations help to organize responses to every-day social challenges.
(31) The application of these ideas to personal-
ity is still in its infancy and requires the development of consistent scales to be related with sound biological markers.
Neuropeptides, social bonding, and early 
rearing practices
Theory and research in the psychobiology of social attachments(8,31)
has linked the impact of early rearing practices (secure/nurturing

has linked the impact of early rearing practices (secure/nurturing 
mothering versus peer rearing or isolation) with the future organization and functioning of several neuroendocrinological systems. This research has mainly explored the function of the central modulatory monoamines norepinephrine, dopamine, and serotonin, and the hypophyseal–adrenal axis responses to social challenges. The evidence has shown that socially deprived monkeys differ physiologically, behaviourally, and cognitively from mother-reared infants in almost every aspect of what it means to be a social monkey; if the privation extends over the ﬁ  rst 6 to 9 months 
of post-natal life, most effects persist into the adulthood. According to Kraemer
(34): ‘The way in which socially deprived individuals

(34): ‘The way in which socially deprived individuals 
orient to and respond physiologically to social stressors is altered and the kind of behavioural differences that seem to be the most important are those usually assigned to the domain of “temperament”’ .
With the addition of the central neuropeptide systems that 
speciﬁ  cally modulate afﬁ  liative tendencies, the study of some cru-
cial experiences during early infancy (and probably adolescence) will provide clues to the clariﬁ  cation of the role that developmental 
processes play in shaping attachment styles. Neural organization depends, to a great extent, on critical environmental inputs to pro-duce enduring behavioural and cognitive adaptation in all domains. Therefore ontogenic factors must be particularly important in modelling social behaviour and in sustaining proﬁ  les of afﬁ  liative

versus non-afﬁ  liative temperaments, in the same way as has already 
been demonstrated for other traits. For instance, in reactive/fearful monkeys, maternal and even grandparental rearing practices can signiﬁ  cantly modify future neuroendocrine and behavioural adap-
tations
(35) with parallel data obtained in rats.(36)
Afﬁ liative genes?
These ﬁ  ndings do not exclude the participation of genetic disposi-
tions in attachment styles. Some authors have suggested that the operation of ‘communicative’ or ‘afﬁ  liative’ genes could prime indi-
vidual tendencies through different sorts of emotional affects.
(37)
There is a paucity of data on the putative genetic basis of particular attachment styles. When a molecular approach has been used,

889
in rodents, to establish a genetic link between variants of the 
vasopressin V1a receptor gene with a conspicuous social behaviour such as monogamous pair bonding, the results have been spect acular. After substituting and inserting the V1a receptor gene characteristic of a monogamous species (the prairie voles), both promiscuous mice and meadow voles adopted the pattern of part-ner preferences and parental behaviours distinctive of the monoga-mous species. It has been shown, in fact, that socio-behavioural trait differences depend on polymorphisms on the regulatory region of the V1a gene.
(38) In rodents and other mammals the 
neurochemical circuits in the brain regulating attachment/afﬁ  lia-
tive behaviours are increasingly detailed. In humans the task is just starting and will deeply inﬂ  uence personality research.
Biodevelopmental processes for 
aggressiveness
Aggressiveness is another temperamental trait that has a very well-

founded biodevelopmental basis.(39) Dimensional descriptions of 
the structure of personality do not always include aggressiveness as a high-level factor, but it is embedded in other traits such as impul-siveness, poor control, or explosive/desinhibited behaviour. However, aggressiveness is a major behavioural trait that has to be taken into account in the routine management of mental disorders, and it is also a prevalent characteristic in personality disorders (generally as an excess, but sometimes because of its absence). In the past, it was extremely difﬁ  cult to prove that individual varia-
tions in aggressive behaviour might be correlated with neurohor-monal characteristics. However, this was because of inadequate methods of quantifying biological and behavioural variations.
(40)
In humans, the link between lifelong aggressive proﬁ  les and

(40)
In humans, the link between lifelong aggressive proﬁ  les and 
familial/subcultural problems is strong indicating that lower socio-economic status, increased rates of abuse, coercive family interactions, and neglect or other adversities contribute to violent behaviour from infancy to adolescence and into adulthood.
(39,41)
But this cannot obscure the effects of enduring biological dispositions that could, in part, result from the inﬂ  uence of socio-
environmental insults to the developing brain. Intensive research in behavioural neuroendocrinology and molecular neuroscience using animal models has shown that aggressive temperaments are associated with both genetic dispositions and critical developmen-tal processes, which affect the function of neuroregulatory controls that either promote or inhibit aggression.
MAO-A functioning and aggression-proneness
It was not surprising, therefore, that an association between a speciﬁ  c gene and an aggressive disorder in humans was early

It was not surprising, therefore, that an association between a speciﬁ  c gene and an aggressive disorder in humans was early 
reported
(42): the males of a Dutch family that carried a mutation of 
the gene for monoaminoxidase A (MAO-A gene situated at chro-mosome Xp11.23) had a record of severe aggressive incidents in different generations. Subsequent investigations in mice showed that ablating the gene for MAO-A resulted in the ‘knockout’ mutants being much more aggressive
(43) MAO plays an important 
part in the breakdown of serotonin and other central monoamines, and previous research in humans had found consistent relation-ships between impulsive or ‘poorly controlled’ behavioural styles and low-MAO activity, a feature also seen in sensation-seekers. A common polymorphism in the promoter region of the MAO-A gene has been shown to interact with early abuse/neglect in lon-
gitudinal studies of large samples of children

(44): only abused kids 
carrying the genetic variant giving low-MAO-A activity are later at risk of antisocial tendencies or violent/criminal behaviour, during adolescence or young adulthood. Further studies with normative samples differentiated by this polymorphism have permitted to map, through structural and functional neuroimaging, cortico-limbic singularities associated with emotional regulation in the low-MAO-A carriers.
(45)
Serotonin/vasopressin ratios
Many other genetically altered animals have been produced that are highly aggressive. Several of them typically show anomalies in sero-tonin function. Knockout mice that do not express the serotonin 5-HT1B receptors are much quicker to attack intruders
(46) an action

(46) an action 
that can be blocked with targeted serotonergic drugs. All this adds to the evidence obtained from mentally ill patients presenting aggres-sive outbursts and from chronic offenders in prisons, which shows an inverse relationship between serotonergic function and violent attacks directed towards others or themselves. Taken together, the data appear to suggest that preserved brain serotonin function helps to attenuate aggressive impulses, probably by blocking other neuro-regulatory systems that promote aggression such as sex steroids, insulin, vasopressin, and others. Vasopressin is involved in the estab-lishment of pair bonds and territorial tendencies in mammals, and promotes aggressive behaviour when social/dominance challenges are perceived. There is evidence from adolescent and juvenile ham-sters showing that proserotonergic interventions attenuate vaso-pressin-induced attacks. Patients with personality disorders
(47)

(47)
showed that cerebrospinal ﬂ  uid levels of vasopressin were positively 
correlated with a life history of aggression, and with attacks against persons in particular. This was a more poweful relationship than the negative one usually obtained from measurements of serotonergic function and aggression. Other neuromodulators help serotonin to attenuate aggressive outputs: in animals, highly speciﬁ  c genetic 
techniques of knocking down or targeted regional brain expression of steroid and oxytocin receptors, have been used to identify ensambles of neuromodulators devoted to control aggressiveness, to the point of postulating a landscape of 50 genes to get a sound description to this function.
(48)
A prospective landscape including 
other traits
T emperamental styles in animals show differential clustering 
of behavioural traits, which correspond to speciﬁ  c (and very 
complex) neurohormonal proﬁ  les. Sometimes, however, a speciﬁ  c

complex) neurohormonal proﬁ  les. Sometimes, however, a speciﬁ  c 
genetic modiﬁ  cation is sufﬁ  cient to promote a fully differentiated 
temperament, as in the case of mice deﬁ  cient in α-calcium–calmod-
ulin-dependent kinase II ( α-CaMKII ) which show decreased fear 
responses and increased defensive aggression associated with low-serotonin levels
(49) (Table 4.12.5.1).
It is possible that this may also hold for exceptional tempera-
mental combinations in humans. However, we have already estab-lished that, when trying to explain the genetic contribution to basic (‘universal’) personality traits, a multigenic/interactional approach is compulsory to explain just part of the measured variance in each trait (Fig. 4.12.5.1). Nevertheless, this contribution can be very 4.12.5 neuropsychological templates for abnormal personalities

SECTION 4  clinical syndromes of adult psychiatry 890
important, as most of research involving twins has yielded 
estimates of just over 40 per cent for the genetic input to typical personality traits, with very modest estimations assignable to the so-called shared (familial/cultural) environment. Non-shared environmental inﬂ  uences (from the womb onwards) and genetic–
environmental interactions make a well-known contribution to each individual temperament. These complex inﬂ  uences may act 
first by modelling the development of basic neuroendocrine regulatory systems that cope with natural and social challenges, and second by shaping the neurocognitive architecture that results in an autonomous and particular lifestyle. An interactional approach along these lines is now laying the foundation for a better description of the different factors that contribute to building the typical proﬁ  les of normal or abnormal personalities.
(50,51)

(50,51)
Such a general scheme must include other traits, in addition to 
the ones considered so far. For instance, the detection of a substan-tial genetic contribution to the baseline level of happiness,
(52)
which all individuals show throughout life independently of the events or episodes that they encounter, must be important for personality diagnoses, because such a ‘calibration point’ has a direct

which all individuals show throughout life independently of the events or episodes that they encounter, must be important for personality diagnoses, because such a ‘calibration point’ has a direct 
relationship with the affective tone of optimism or pessimism. Moreover, other traits and measures in the domain of cognitive performance (e.g. attentional spans, perceptual/appraisal reliability, thinking styles, and memory biases) or of character (e.g. religiosity/transcendence, conservatism, altruism, self-directness/self-esteem, and the drive to achieve/enthusiasm) should be incorporated into the whole description of personality structure. This is essential if the aim is to produce a general framework powerful enough to contain the complex categories that clinicians have tried to construct on the basis of systematic observation for more than a century. Cloninger
(8,11) and others have advanced proposals along these

(8,11) and others have advanced proposals along these 
lines, which have functioned as useful steps to guide empirical work. It must be added that structural and functional neuroimag-ing techniques have been used to map relations between personal-ity dimensions and brain’s regional organization and patterns of activation/deactivation. Although these studies are very preliminary and have been done with convenient samples, they have offered hints of neurocognitive architectures, which tend to conﬁ  rm, on 
a broad basis, the neurochemical mechanisms behind the main temperamental traits.
(53–55)
Sophisticating the diagnoses of 
The evidence discussed so far is starting to have a major impact on 
the reconceptualizing of the approach that has been applied in psy-chiatry to the detection and categorization of the elusive proﬁ  les of

the reconceptualizing of the approach that has been applied in psy-chiatry to the detection and categorization of the elusive proﬁ  les of 
normal and abnormal personalities. It is clear that anchoring some temperamental traits to a sound genetic or biodevelopmental base, and accruing a plausible neurocognitive architecture for it, will not provide a complete solution to the problems encountered in the aetiology and diagnosis of personality disorders. Many additional steps will have to be worked out. But in view of the increasing links that are being established between core personality traits and some genetic/developmental mechanisms, the task of building a solid neuropsychological framework, which would allow improved identiﬁ  cation and differentiation of abnormal personali-
ties no longer seems hopeless. In fact, such research is opening up many new avenues for understanding the effects of different factors 
(innate dispositions, neurodevelopmental organization, neurocog-

nitive architectures, critical social transitions, and repeated stress episodes) on an individual’s vulnerability to developing a personality 
disorder.
Hence, the use of behaviourally well deﬁ  ned and biologically 
well-established personality measures must be the starting point 
for achieving the ﬁ  ne-tuned diagnoses increasingly required in 
modern medicine. Complexity in measurement will increase, but 
there is no other way of obtaining data that are sufﬁ  ciently valid 
to allow understanding of the classical personality disorders. It is 
hoped that advances in the neuropsychological detection of the more salient ‘clinical’ proﬁ  les within each of the personality sub-
spaces or ‘clusters’ (at the level of either traits or dimensions), together with a reﬁ  nement of the neurocognitive and neurohor-

monal data, will produce much better solutions. Some of the old-established and consistent categories of personality disorders will be conﬁ  rmed, but it is possible that unexpected ‘types’ of abnormal 
personalities, with clinical relevance, will emerge. In this new Table 4.12.5.1  Summary of behavioural phenotypes in α-CaMKII 
mutant mice
Behavioural phenotype Heterozygote Homozygote
Fear-related responses Decrease Decrease
Offensive aggression Normal DecreaseDefensive aggression Increase DecreasePain sensitivity Normal IncreaseStartle response Normal IncreaseVigilance Normal IncreaseMating Decrease DecreaseMaze learning Normal Decrease
Reproduced from C. Chen et al. Abnormal fear response and aggressive behaviour in mice 
deﬁ  cient for alpha–calcium–calmodulin–leinase II. Science , 266, 291–4, copyright 1994,

deﬁ  cient for alpha–calcium–calmodulin–leinase II. Science , 266, 291–4, copyright 1994, 
with permission from the American Association for the Advancement of Science.
Fig. 4.12.5.1 Two views of the relationships between genes and personality. 
A. Early studies looked for linear relationships between gene markers and 
temperamental traits or high-order personality factors. B. Reality is likely to be 
far more complex with gene networks interacting with environmental inputs impacting on brain development and leaving enduring neural dispositions that, 
in turn, inﬂ  uence behavioural, cognitive, and affective styles (temperamental 
traits). (Reproduced from D. Harner. Rethinking behavior genetics, Science , 298, 
71–2, copyright 2004, with permission from the American Association for the Advancement of Science.).Temperamental traits/ 
High-order
personality factors. 
Temperamental traits:

       fearfulness, novelty-,
seeking, aggressiveness,empathy, altruism,
extraversion, persistence,
conservatism, religiosity,resilience…
Brain

891
framework it may be easier perhaps to detect at an early stage those 
‘exceptional’ and ‘charismatic’ , although anomalous, personalities who often impose great social costs and dramatic consequences not only for themselves but also for the group or the society in which they live.
(56)
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4.12.6 Psychotherapy for 
Psychotherapy has historically been the mainstay of treatment for 
personality disorder (PD). It remains so. Psychoanalysis was prob-ably the earliest formal treatment for PD, which led to the ﬁ  rst

personality disorder (PD). It remains so. Psychoanalysis was prob-ably the earliest formal treatment for PD, which led to the ﬁ  rst 
clinical descriptions of borderline personality disorder. A parallel but linked development was the application of psychoanalytic ideas in therapeutic communities which have been in existence for over 60 years and remain a treatment context and method for patients with PD. It was only in the 1960s that modiﬁ  ed psychotherapeutic 
treatments were developed. Initially these were based on psychody-namic understanding of PD, but gradually other theoretically and practically driven models have developed, leading to the current situation in which there are behavioural, cognitive, dynamic, and supportive treatments offered in a range of contexts. Some of these methods have more empirical support than others. These methods 
will be described in this chapter.
Psychological therapies for personality disorders take place

Psychological therapies for personality disorders take place 
against the background of the natural course and outcome of the disorder. Until recently, the natural history of personality disorder had not been systematically studied. Several major cohort follow-along studies have yielded surprising data concerning the rate of symptomatic remissions in a disorder that was assumed to have a lifelong course.
(1) For example, over a 10-year follow-along period, 
88 per cent of those initially diagnosed with borderline personality disorder appeared to remit in the sense of no longer meeting DIB-R or DSM-III criteria for BPD for 2 years.
(2) The symptoms

(2) The symptoms 
that remit most readily, irrespective of treatment, appear to be the acute ones, such as parasuicide and self-injury, which are the most likely to trigger psychotherapeutic intervention. T emperamental symptoms, such as angry feelings and acts, distrust and suspicion, abandonment concerns, and emotional instability, appear to resolve far more slowly. In the Collaborative Longitudinal Personality Disorder Study (CLPS),
(3) when remission was deﬁ  ned as 12 months 
at two or fewer criteria for PDs, over half of BPD and 85 per cent of major depressive disorder (MDD) patients were reported to remit over a 4-year period. Psychosocial functioning recovered far more slowly than acute symptoms.
(1)
There is a considerable body of literature on psychotherapeutic

(1)
There is a considerable body of literature on psychotherapeutic 
interventions for personality disorders, but signiﬁ  cant evidence

893
for effective treatment remains sparse. Much of the literature is 
dominated by expert opinion, which is not invariably the most helpful guide. In this chapter, we focus on psychological treatments where at least some evidence for treatment effectiveness exists. The evidence is strongest for borderline personality disorder (BPD). Treatment of some other personality disorders, for example schiz-oid, narcissistic, obsessive–compulsive, dependent, is evidenced mainly by clinical case reports in which theory is combined with clinical description and where, if outcome is measured at all, it is measured for the purpose of illustration and has little probative value.
Assessment of treatment
Any study that seeks to demonstrate the effectiveness of a treat-ment for PD must fulﬁ  l the following requirements:
(a)Carefully deﬁ  ne the target population . This can be problematic, 
because the deﬁ  nition of personality disorder (PD) remains

because the deﬁ  nition of personality disorder (PD) remains 
controversial, and there is little evidence that the categories of personality disorder have any predictive value in determining response to treatment. Comorbidity must also be considered. Lifetime comorbidity should not be an exclusion criterion for studies, but there is an argument for excluding individuals with current comorbidity. However, in clinical practice, such exclusion is almost impossible.
(b)Adequately deﬁ  ne the treatment and assessment of its speciﬁ  city.
Personality disorder is a multifaceted condition that is sus-ceptible to a variety of inﬂ  uences, and it justiﬁ  es the use of 
complex interventions. These require complex evaluations, which increase the difﬁ  culty of interpreting results.
(c)Establish that treatment is superior to no treatment  since per-
sonality disorders show gradual improvement over time.

(d)Take account of Axis I disorders . This can be done by excluding 
patients with Axis I disorders, but PDs are almost always asso-ciated with signiﬁ  cant Axis I psychopathology. An alternative, 
which no trial has, to date, attempted, would be to assign patients to treatment group on the basis of matched Axis I disorders. In any case, it must be demonstrated that treatment impacts on personality rather than merely causing a change in mood or psychiatric symptoms.
(e)Include adequate follow-up , as some trials report reduced treat-
ment effects during follow-up.
(f) Address cost-effectiveness  relative to alternative interventions.
(g)Study treatment effects in standard practice  (pragmatic trials) as 
well as under strict experimental conditions.
Research trials investigating the effectiveness of treatments for

Research trials investigating the effectiveness of treatments for 
personality disorder have so far singularly failed to meet most of these requirements.
Adverse effects of psychotherapy for 
It is possible that some psychosocial treatments for personality dis-
order may have impeded the patient’s capacity to recover following the natural course of the disorder and/or prevented them from taking advantage of changes in social circumstances. In Stone’s
(4)
classic follow-up of patients treated nearly 40 years ago, a 66 per cent recovery rate was only achieved in 20 years, about four times

(4)
classic follow-up of patients treated nearly 40 years ago, a 66 per cent recovery rate was only achieved in 20 years, about four times 
longer than reported in the more recent studies. It seems unlikely that the nature of the disorder has changed or that treatments have become markedly more effective rather it is possible that treat-ments with these adverse effects are being offered less frequently now than in the past, perhaps because of changed patterns of health 
care, particularly in the United States.
Meta-analyses of psychotherapy and 
psychosocial treatments
It remains unclear whether the literature is robust enough to with-
stand the methodology of meta-analysis. The lack of good quality studies, especially randomized trials, the small number of patients in the trials, the heterogeneity of the personality disorders studied, and the variability of outcome measures across studies means that conclusions must remain tentative. One meta-analysis
(5) included

(5) included 
15 studies that reported data on pre- to post-treatment effects and/or recovery at follow-up, including three randomized, controlled tri-als, three randomized comparisons of active treatments, and nine uncontrolled observational studies. They included psychodynamic/interpersonal, cognitive behavioural, mixed, and supportive thera-pies. All studies reported improvement in personality disorders with treatment. The mean pre–post effect sizes within treatments were 1.11 for self-report measures and 1.29 for observational measures. Among the three randomized, controlled treatment trials, activepsychotherapy was more effective than no treatment according to self-report (ES = 0.75), though none of the controls employed an active therapy. Only four studies reported the percentage of cases no longer meeting the criteria for personality disorder. At follow-up(at a mean of 67 weeks), 52 per cent met this criterion. Treatment length was associated with the likelihood of recovery.

A subsequent meta-analysis
(6) included psychodynamic therapy 
and cognitive behaviour therapy (CBT) in the treatment of personality disorders. There were 22 studies of psychodynamic therapy and CBT published between 1974 and 2001 that (1) used standardized methods of diagnosis, (2) applied reliable and valid instruments for the assessment of outcome, and (3) reported data that allowed calculation of within-group effect sizes or included assessment of recovery rates. Because only 11 of the 22 studies were RCTs, ESs were calculated on the basis of pre- to post-therapy change. Fourteen studies included psychodynamic therapy, and 11 studies included CBT. The psychodynamic studies had a mean follow-up of 1.5 years, compared to only 13 weeks for CBT. Psychodynamic therapy yielded an overall effect size of 1.46 ( k = 15 
contrasts), with effect sizes of 1.08 for self-report measures and 
1.79 for observer-rated measures. For CBT ( k = 10 contrasts), the

1.79 for observer-rated measures. For CBT ( k = 10 contrasts), the 
corresponding values were 1.00, 1.20, and 0.87. For more speciﬁ  c 
measures of personality disorder pathology, a large overall effect size (1.56) for psychodynamic therapy suggested long-term rather than short-term change in personality disorders. For BPD, the ES for psychodynamic therapy was 1.31 ( N = 8), and for CBT 0.95 
(N = 4). Treatment length showed a positive but noºnsigniﬁ  cant 
correlation with outcome in psychodynamic studies ( r = 0.41); 
there were too few CBT trials for an equivalent analysis. In the 5 years since 2001, there have been nearly as many new randomized trials of treatments for personality disorder as were included in this meta-analysis, so a further systematic review including only randomized trials is due.4.12.6 psychotherapy for personality disorder

SECTION 4  clinical syndromes of adult psychiatry 894
Psychotherapy for borderline personality 
disorder (BPD)
Several psychosocial treatments for BPD have emerged over the 
past decade, with one US guideline recommending psychotherapy as the primary treatment for this condition.
(7) It is impossible to 
recommend one specific therapy, because information from research remains inadequate. It has become clear not only that several treatments may be of use, but also that any one treatment by itself, is helpful in only about a half of all cases.
(8) Also, there is 
general consensus that some of the nonspeciﬁ  c elements of psy-
chotherapy may be as important in determining the success of a treatment as the speciﬁ  c techniques. We reviewed treatments shown 
to be moderately effective and concluded that they share certain common features.
(9) They tend to (a) be well-structured, (b) devote

(9) They tend to (a) be well-structured, (b) devote 
considerable effort to enhancing collaboration, (c) have a clear focus, (d) be theoretically highly coherent to both therapist and patient, (e) be relatively long-term, (f) encourage a powerful attach-ment relationship between therapist and patient, and (g) be well integrated with other services available to the patient. While some of these features may seem to pertain more to a successful research study rather than a successful therapy, the manner in which clinical treatment pro tocols are constructed and delivered is probably as important in the success of treatment as the intervention itself.
(a) Dynamic psychotherapy
Dynamic psychotherapy has long been recommended for BPD and has now been modiﬁ  ed to target the characteristic features of 
the disorder. Almost all of the ﬁ  rst studies examined inpatient

the disorder. Almost all of the ﬁ  rst studies examined inpatient 
treatment using prospective one group pre- to post-test designs.
(10)
These studies failed to rule out other plausible causes of change, such as passage of time or subsequent outpatient treatment. Stone’s
(11) report of up to 20 years follow-up of 550 inpatients, 
most of whom had received some sort of psychosocial interven-tion, indicated that 66 per cent of patients were functioning well. However, a naturalistic 5-year follow-up of individuals receiving inpatient treatment at the Cassel Hospital in London indicates the need for caution in ascribing beneﬁ  ts to inpatient treatment.
(12)
Whilst longer term follow-ups are to be applauded, they are hard 
to interpret, because other therapies are often given subsequent to the original treatment.

(12)
Several nonrandomized trials of dynamic psychotherapy have been 
undertaken by Stevenson, Meares, and colleagues. In an open trial for 48 patients receiving twice-weekly interpersonal-psychodynamic outpatient therapy for 12 months,
(13) 30 per cent of the treatment 
group no longer met DSM-III-R criteria for BPD, while the waiting-list group changed little. Cost–beneﬁ  t analysis found signiﬁ  cant 
reduction in costs, largely attributable to reduced inpatient stays. A replication study
(14) also found signiﬁ  cant reduction in symptom 
severity with the same treatment.
A randomized study of 38 patients with BPD compared an 
18-month programme of partial hospitalization using mentalization-based treatment (MBT) with standard psychiatric care.
(15)

(15)
Mentalization entails making sense of the actions of oneself and others on the basis of intentional mental states such as desires, feelings, and beliefs. Outcome measures included frequency of suicide attempts, acts of self-harm, number and duration of inpa-tient admissions, use of psychotropic medication, and self-report measures including depression, interpersonal function, and social adjustment. After 6 months, patients given MBT showed a statisti-
cally signiﬁ  cant decrease on all measures in contrast to the control

cally signiﬁ  cant decrease on all measures in contrast to the control 
group which showed limited change or deterioration over the same period. This was sustained at the end of the 18 months of treatment and showed further improvement on follow-up after another 18 months. Long-term follow-up 5 years after the initial treatment suggested that the differences between the groups continued, but general social function remained impaired in both groups.
(16) The treatment was cost-effective and has been 
manualized,(17) but as yet the active components remain unclear,

manualized,(17) but as yet the active components remain unclear, 
and it has not been shown that positive outcomes are correlated with an improvement in mentalizing. (An outpatient version of MBT is currently being evaluated for borderline and antisocial PD in a further randomized controlled trial.) Although promising, this treatment needs further validation by research carried out independently of the originators. Favourable data has recently become available on the effectiveness of a similar programme established in the Netherlands.
(18)
Transference-focused psychotherapy (TFP) has also shown good 
results. In a cohort study,(19) 23 female borderline patients were 
treated for 12 months. Compared with the year before treatment, the number of patients who made suicide attempts decreased signiﬁ  cantly, as did the medical risk and severity of self-injurious

treated for 12 months. Compared with the year before treatment, the number of patients who made suicide attempts decreased signiﬁ  cantly, as did the medical risk and severity of self-injurious 
behaviour. Also, compared with the previous year, there were signiﬁ  cantly fewer hospitalizations and fewer days of psychiatric 
hospitalization. However, one in ﬁ  ve patients dropped out of
treatment. A subsequent trial compared TFP , DBT, and supportive therapy.
(20) Ninety patients (all but nine of whom were women) 
were randomized. At the end of 1 year of treatment, the groups did not differ on global assessment of functioning, social adjustment, scores of depression and anxiety, and measures of self-harm. TFP patients improved signiﬁ  cantly more than those receiving DBT or 
supportive therapy on irritability and verbal and direct assault. Patients who received TFP improved most in reﬂ  ective function, an 
operationalization of the mentalization construct,
(21) but it is not

(21) but it is not 
known whether improved reﬂ  ective function relates to treatment 
gains at follow-up.
Schema-focused therapy (SFT) has been compared with TFP .(22)
Treatment was given by therapists with approved training in the 
treatment methods administered treatment to 88 patients with borderline personality disorder. In an ‘intent to treat’ analysis, patients who received TFP showed signiﬁ  cantly less improvement

treatment methods administered treatment to 88 patients with borderline personality disorder. In an ‘intent to treat’ analysis, patients who received TFP showed signiﬁ  cantly less improvement 
than those who received schema-focused CBT over 3 years, and TFP was more expensive. Both groups showed improvement, but changes in the combined measure of outcome in the schema-focused therapy group were greater and more prolonged than in the TFP group. There are several reasons for caution regarding these conclusions. (i) Differences in outcome between the groups can be accounted for almost entirely by the larger dropout early in treat-ment of patients treated with TFP and disappear when ‘completers’ are compared. It would be valuable to know why more patients dropped out from TFP at an early stage than from SFT. (ii) Follow-
up is required to determine whether treatment gains and group

up is required to determine whether treatment gains and group 
differences are maintained. (iii) In the duration of the treatment period, around 40 per cent of patients could be expected to improve without the treatment.
(23) This study also raises the question of 
how successfully a treatment (TFP) from the US can be transported to a European context.

895
(b) Group psychotherapy
Noncontrolled studies of day hospital stabilization followed by 
outpatient dynamic group therapy indicate its utility for BPD.(24)
Marziali and Monroe-Blum used group therapy focused on relationship management and without the milieu and social components. A randomized controlled trial found equivalent results between group and individual therapy, suggesting that group therapy is more cost-effective.
(25) Further studies are needed 
to conﬁ  rm their ﬁ  ndings, especially since dropout rates were high.
(c) Cognitive analytical therapy (CAT)
CAT has been manualized for treatment of BPD, and many are 
enthusiastic about its effectiveness. There are some indications that it may be effective. In a series of 27 patients with borderline personality disorder treated with 24 sessions of CAT, half no longer met diagnostic criteria for personality disorder at 6-month follow-up.
(26) More deﬁ  nitive statements about efﬁ  cacy await results of a

(26) More deﬁ  nitive statements about efﬁ  cacy await results of a 
randomized trial in progress. Ryle (personal communication) has indicated that patients treated with CAT showed significant improvement on a range of clinical measures but reported no difference between people receiving CAT and those undergoing other
psychological treatments. Thus, the effects may be nonspeciﬁ  c. 
A second randomized trial is in progress comparing CAT with ‘best available standard care’ for adolescent patients with border-line personality disorder.
(27)
(d) Cognitive therapy
Cognitive behavioural formulations of BPD are diverse. In a model derived from ‘standard’ CBT and modiﬁ  ed for personality disorders, 
Beck and associates
(28) deﬁ ne personality in terms of patterns of

(28) deﬁ ne personality in terms of patterns of 
social, motivational, and cognitive-affective processes, thereby mov-ing away from a primary emphasis on cognitions. However, person-ality is considered to be determined by ‘idiosyncratic structures’ , known as schemas, whose cognitive content gives meaning to the person, and these schemas are the cornerstone of cognitive formulations of BPD. Y oung
(29) has developed a treatment

(29) has developed a treatment 
programme for BPD based on early maladaptive schemas (EMS). These are stable, enduring patterns of thinking and perception that begin early in life and are continually elaborated. EMS are unconditional beliefs linked together to form the core of an individ-ual’s self-image. Challenge to these beliefs threatens the core identity which is defended with alacrity, guile, and desperation since activa-tion of the schemas may evoke aversive emotions. The EMS give rise to ‘schema coping behaviour’ , which offers the best adaptation to living that the borderline has found. Schema-focused therapy (SFT) is only just being evaluated, but its adherence to the general require-ments of an effective treatment enumerated above suggests that it should be reasonably successful. The recent report comparing SFT with TFP
(22) is described above, but SFT has yet to be shown to be

(22) is described above, but SFT has yet to be shown to be 
more effective than treatment as usual. It is possible that TFP simply induced more negative effects in patients than SFT.
A small ( N = 34), randomized controlled trial assessed brief cogni-
tive therapy, linked to a manual and incorporating elements of dia-lectical behaviour therapy, in the treatment of recurrent self-harm in people with cluster B personality difﬁ  culties and disorders.
(30)
Manual-assisted cognitive treatment  (MACT) is a complex six-
session treatment based on the theory that deliberate self-harm and suicide attempts stem from distorted cognitive schemas and coping skills deﬁ  cits.
(31) It incorporates elements of bibliotherapy, 
CBT, and DBT, as well as psychoeducation in relation to self-harm and suicide attempts, and a functional analysis of speciﬁ  c episodes.

The treatment also involves strategies to regulate emotion, such as distraction, crisis planning, and problem-solving strategies. Cognitive restructuring strategies and management of negative thinking are incorporated in the second phase of the programme, which includes components for the management of substance abuse and relapse prevention. Its brevity makes MACT a poten-tially valuable intervention from a public health standpoint. In a clinical trial, 34 self-harm repeaters with a parasuicide attempt in the preceding 12 months were randomly allocated to MACT or treatment as usual (TAU). The rate of suicide acts was lower with MACT, and self-rated depressive symptoms also improved. The mean treatment time was 2.7 sessions, and the average cost of care was 46 per cent less with MACT. A subsequent larger study (N = 480) did not ﬁ  nd evidence that time to repeat parasuicide 
was extended following MACT, although there was a decrease in 
the cost of care.

(32) A randomized controlled trial with 104 people 
with borderline personality disorder with a longer period of treat-ment (up to 30 sessions) found signiﬁ  cant beneﬁ  t with regard to 
suicidal behaviour but a nonsigniﬁ  cant increase in emergency pre-
sentations in the cognitive behaviour therapy group.
(33) The CBT 
arm used less resources, although no signiﬁ  cant cost-effectiveness 
advantage was demonstrated. Those who received CBT showed less evidence of dysfunctional beliefs, lower state anxiety scores, and less positive symptom distress.
Systems training for emotional predictability and problem solving
(STEPPS)
(34) is a group treatment offered as an adjunct to other

(STEPPS)
(34) is a group treatment offered as an adjunct to other 
treatments rather than as a sole intervention. It is a 20-week manual-ized programme of psychoeducation and behavioural management focusing on maladaptive schemas and including both professional and family carers. Subjects are encouraged to continue their usual care, including individual psychotherapy, medication, and case man-agement, and are required to designate a mental health professional who would provide ongoing care and could be reached in a crisis. Data from 52 patients suggests some reduction in impulsive and sui-cidal behaviour and some improvement on meas ures of depression, but no follow-up data is yet available. An RCT is currently ongoing. In Holland, a retrospective assessment of the experience of 85 patients enrolled in STEPPS groups
(35) reported signiﬁ  cant improve-

ment on all subscales of the SCL-90, particularly those assessing anxi-
ety, depression, and interpersonal sensitivity. Patie nts and therapists 
reported moderate to high levels of acceptance for the treatment in both studies. As most of the effective programmes for BPD are long-term and expensive, a short-term efﬁ  cacious treatment will be of 
great value. However, even if found to be effective in a clinical trial, its effectiveness will depend on the nature of the treatment as usual.
(e) Dialectical behaviour therapy (DBT)
DBT is a special adaptation of CBT, originally used for the treat-ment of a group of repeatedly parasuicidal female patients with borderline personality disorder. DBT is a manualized therapy
(36)

(36)
which includes techniques at the level of behaviour (functional analysis), cognitions (e.g. skills training), and support (empathy, teaching management of trauma), with a judicious mix of ideas derived from Zen Buddhism. The initial aim of DBT is to control self-harm, but its main aim is to promote change in the emotional 4.12.6 psychotherapy for personality disorder

SECTION 4  clinical syndromes of adult psychiatry 896
dysregulation that is judged to be at the core of the disorder. Thus, 
the goal of DBT goes far beyond self-harm reduction. The ﬁ  rst 
trial(37) involved 44 females with borderline personality disorder 
who had made at least two suicide attempts in the previous 5 years, with one in the preceding 8 weeks. Half were assigned to DBT and half to the control condition. Assessments were made during and at the end of therapy and at a 1-year follow-up. Control patients were signiﬁ  cantly more likely to attempt suicide spent signiﬁ  cantly 
more time as inpatients over the year of treatment (mean 38.8 and 8.5 days, respectively), and were signiﬁ  cantly more likely to drop out 
of the therapies to which they were assigned (attrition 50 per cent versus 16.7 per cent, respectively).
DBT was less superior at the 1-year follow-up. Follow-up was

DBT was less superior at the 1-year follow-up. Follow-up was 
naturalistic, because the morbidity of the group was thought to preclude termination of therapy at the end of the experimental period. At 6-month follow-up, DBT patients continued to show less parasuicidal behaviour than controls, though there were no between-group differences in days in hospital. At 1 year there were no between-group differences in suicidal behaviour, but DBT patients had had fewer days in hospital. Treatment with DBT for 1 year compared with treatment as usual led to a reduction in the number and severity of suicide attempts and decreased the frequency and length of inpatient admission. However, there were no between-group differences on measures of depression, hope-lessness or reasons for living.
The widespread adoption of DBT for BPD and other PDs is

The widespread adoption of DBT for BPD and other PDs is 
a tribute to both the effectiveness of the treatment and its accept-ability to patients and families. Several studies have replicated the original Linehan study. Turner observed a decrease in parasuicidal acts and deliberate self-harm at 6 and 12 months in 12 patients treated with DBT compared to 12 treated with client-centred therapy.
(38) Koons and colleagues(39) compared DBT with outpa-
tient treatment as usual in 28 participants and found decreases in frequency of parasuicidal acts and self-injury at 3 and 6 months. Bohus and colleagues
(40) explored an inpatient adaptation of DBT 
and found signiﬁ  cant improvement in deliberate self-harm but 
a higher dropout rate. Other studies, however, have shown DBT to be no better than other active treatments such as the 12-step programme for opioid dependence
(41) or treatment as usual in a 
UK context.(42)
Because of severity, symptomatology, and high rates of co-occurring

disorders, BPD affects family members, and interventions address-ing the needs of family members have been developed using a DBT frame.
(43) In a study of a 12-week community-based BPD family 
education programme, Family Connections (FC),(44) family 
members showed signiﬁ  cant improvements on burden, grief and 
empowerment, and a reduction in depression. However, the long-term effect of family interventions on the patient’s well-being remains to be demonstrated.
It is uncertain which are the active elements of DBT-individual 
psychotherapy whether skills training, phone consultation, or the consultation team. Two studies examining the process of change in DBT
(41,45)  had inconclusive results. Nevertheless, adding a DBT

(41,45)  had inconclusive results. Nevertheless, adding a DBT 
skills training group to outpatient individual (non-DBT) psycho-therapy does not seem to enhance treatment outcomes. Given that DBT is described as primarily a skills training approach, this ﬁ  nd-
ing might indicate that the central skills training component of DBT may not be of primary importance. However, individual DBT focuses on the strengthening of skills learned in the skills groups, and trying to combine a skills training group with an individual

therapy that ignores or pays minimal attention to skill strengthen-ing, may invalidate what the patient has learned about utilizing learned skills in an attempt to cope with everyday functioning. Disagreement remains regarding the policy of not admitting patients to hospital, except for a minimum period, since some stud-ies show that the time and structure of an inpatient setting can be 
used to apparently good effect.
(46)
(f) Therapeutic community treatments
A therapeutic community (TC) may be deﬁ  ned as an intensive

A therapeutic community (TC) may be deﬁ  ned as an intensive 
form of treatment in which the environmental setting provides the core means through which behaviour can be challenged and modi-fied, essentially through group interaction and interpersonal understanding. Therapeutic communities are described in Chapter 6.3.9. Several studies have been completed at the Cassel Hospital, a tertiary referral centre with a psychosocial residential treatment programme which includes daily unit meetings, community meetings, structured activities, co-responsibility planning for the running of the therapeutic community and other structured activities, and formal psychoanalytic psychotherapy (individual and small group). Patients in two different specialist psychosocial programmes (step-down and long-term inpatient) and in general psychiatric treatment as usual (TAU) were assessed at 12 and 24 months. By 24 months, patients in the step-down condition showed signiﬁ  cant improvements on all measures.

(47) Patients in 
the long-term residential condition showed signiﬁ  cant improvements
in symptom severity, social adaptation, and global functioning but no changes in self-harm, attempted suicide, and readmission rates. Over the same period, patients in the TAU group showed no improvement on any variable except self-harm and hospital readmissions. All three groups were followed for 72 months after intake. The specialist step-down condition led to signiﬁ  cantly 
greater change than either the solely inpatient model or TAU in most key dimensions of functioning, ev en 5 years aft er the 12 months 
hospitalization.
(48)
While the study appears to show that a step-down programme 
leads to signiﬁ  cant improvement, this conclusion should be quali-
ﬁ ed by the study’s design limitations, including the lack of random

ﬁ ed by the study’s design limitations, including the lack of random 
assignment to the three conditions and the naturalistic geographi-cal allocation. Overall, these findings are consistent with the general view that extended hospital admission, even to a psycho-therapeutically oriented unit, may engender pathological depen-dency and regression. Against this, a prospective study of 216 
patients with severe personality disorder treated at the Menninger 
Clinic in two psychoanalytically orientated inpatient units
(49)
found positive change at discharge and 1 year follow-up, with no evidence of deleterious effects due to regression and dependency. As there are now many treatments for personality disorder, thera-
peutic communities must be evaluated by comparison studies 
using acceptable experimental designs if they are to be considered a

using acceptable experimental designs if they are to be considered a 
serious treatment approach.
(g) Nidotherapy
Nidotherapy is the name of a new form of systematic management 
for chronic and persisting mental disorders that concentrateson making environmental changes to bring about a better ﬁ  t 
between person and environment.
(50) All types of environmental 
change—physical, social, and personal—are considered relevant.

897
Nidotherapy is a collaborative treatment ‘involving the systematic 
assessment and modiﬁ  cation of the environment to minimize the 
impact of any form of the disorder on individual or on society’ .(50)
The word is derived from the Latin nidus or nest, an environment adapted to the object that is occupying it. The therapeutic aim is not to change the person but rather to change the environment so it better ﬁ  ts the person. The therapist should repeatedly question 
whether interventions given in the course of management incorpo-rate analytic, cognitive, or behavioural psychotherapy—if they do, the intervention is no longer nidotherapy. Nidotherapy involves seeing the world from the patient’s standpoint, joint planning of agreed environmental targets, a concentration on ﬁ  nding ways to 
improve social function, sharing responsibility for the programme so that the patient is the ﬁ  nal owner, and the use of independent

improve social function, sharing responsibility for the programme so that the patient is the ﬁ  nal owner, and the use of independent 
arbitrators to resolve disagreements about the change that is needed. The programme has several phases: identiﬁ  cation of the boundar-
ies of the nidotherapy, full environmental analysis, implementation of agreed environmental change, monitoring progress, and reset-ting targets. It addresses the patient’s physical, social, and personal environments.
This therapy is at its early stages, with little other than anecdotal 
evidence.
(51) Nevertheless, it represents a healthy contrast to the

evidence.
(51) Nevertheless, it represents a healthy contrast to the 
behavioural, cognitive, and analytic approaches which dominate most psychosocial interventions. There is no doubt that a person’s environment is an important determinant of their experience and behaviour. This is accepted regardless of theoretical perspective, yet none of these perspectives offers a model of how environments should be modiﬁ  ed to be more in line with the capacities of the 
person who exists within them. Modifying situational constraints may indeed be an independent and effective adjunct to other treat-ment protocols for personality disorder.
(h) Summary
The ﬁ  ndings from the above studies suggest that some of the prob-

lems encountered by people with BPD may be amenable to talk-ing/behavioural treatments. Several studies show that the effort by the recipient of care in sticking with the care package is rewarded by a decline in anxiety, depression, self-harm, hospital admission, and use of prescribed medication. A review using Cochrane meth-odology
(52) concluded that the studies are too few and too small to 
justify full conﬁ  dence in their results so that current therapies 
remain experimental. The reviewers suggest that people with BPD, if offered entry into a randomized study of therapies, may wish to consider that outcomes of both experimental and control groups will probably be better than those of standard care outside the trial.
Psychotherapy for avoidant personality disorder
Avoidant PD is the most prevalent personality disorder in the general population.
(53) However, avoidant personalities tend to

(53) However, avoidant personalities tend to 
suffer quietly and reject emotional involvement with others. Nevertheless, their distress and functional impairment are proba-bly comparable to those of people with BPD.
Studies of the efﬁ  cacy of treatment for avoidant PD have been 
hampered by the close connection of the condition to social phobia. About half of avoidant patients also have a social phobia. There is controversy over the distinction between generalized social phobia and avoidant personality disorder, many authors regarding the latter as an exaggerated type of social phobia.
(54) Many studies of social phobia include individuals with avoidant personality dis-

order. Few trials explicitly focus on this disorder. Most APD patients are treated using behavioural methods including exposure, social skills training, and systematic desensitization. Early studies suggested treatment gains that were maintained for up to 1 year after ﬁ  nishing active treatment.
(55)
For phobic anxiety, there is some agreement that the cognitive 
behavioural strategies involved in traditional treatment tend some-times to fail with the more severely disturbed patients because of resistance evoked by maladaptive personality traits.
(56) Most stud-
ies report a pattern of outcome similar to that for generalized social phobia, with similar rate of gains to those without APD but lower end-point functioning,
(57) though some report a slower rate of 
change.(58) Massion et al .(59) report a 5-year prospective study

change.(58) Massion et al .(59) report a 5-year prospective study 
examining the impact of personality disorders in 514 patients in the Harvard/Brown anxiety research programme. The presence of a personality disorder reduced the probability of remission in social phobia by 39 per cent. Much of this reduction was explained by the presence of avoidant personality disorder. Alden
(60) found that 
while there were signiﬁ  cant improvements on a range of measures, 
only 9 per cent of patients treated for APD rated themselves as completely improved.
Therapeutic strategies for severe cases of APD should be tailored

Therapeutic strategies for severe cases of APD should be tailored 
to the core pathology of the disorder—(1) a despised and unwor-thy sense of self connected to a punitive and blaming internal other; (2) an avoidant interpersonal style; (3) affect phobia; and (4) pseudomentalization (intellectualization and pretend relations). In achieving somewhat better functioning for avoidant patients, short-term dynamic psychotherapy and cognitive therapy have been shown to have good results.
(61) For the more severely 
disturbed avoidant patients, day treatment programmes are prob-ably more effective
(62) than outpatient therapy, where they tend to 
ossify.(63) An RCT of cognitive behaviour therapy versus psychody-
namic therapy for AVPD(64) found greater beneﬁ  t from cognitive

namic therapy for AVPD(64) found greater beneﬁ  t from cognitive 
behaviour therapy. Interpersonal therapy and supportive-expressive therapy have also been tried. Patients are often reported to have made substantial gains in all treatment programmes,
(65)
but many patients who complete treatment still demonstrate a low level of social function.
Psychotherapy for antisocial personality 
disorder (ASPD)
There are few evaluated therapies for ASPD. The disorder is a 
common comorbid diagnosis for individuals with substance abuse problems,
(66) and a small number of trials have contrasted 
those with ASPD alone with those with ASPD and depression in the treatment of substance misuse. Outcomes with antisocial personality disorder alone are often poorer than when ASPD is associated with depression. Three studies
(67–69)  have reported

(67–69)  have reported 
that ASPD alone was an obstacle in the treatment of substance misuse.
Several studies (though few controlled trials) have examined
the impact of treatment on individuals within the penal system, at least some of whom, it is likely meet criteria for antisocial person-ality disorder. Most studies focus on speciﬁ  c categories of offend-
ing behaviour (e.g. sexual offences), or on prisoners with problem behaviours, particularly violence.
(70) Some studies have focused 
on individuals who manifest callous-unemotional traits.(71)4.12.6 psychotherapy for personality disorder

SECTION 4  clinical syndromes of adult psychiatry 898
There are a few observational studies of individuals detained in 
high security settings using group CBT,(72) individual and group 
CBT in the context of a therapeutic milieu,(73) or psychodynamic 
therapy.(74) While improvements in functioning are noted, there 
are severe methodological problems such as the absence of control groups and highly reactive measurement of outcome.
Studies reviewed by Warren and colleagues
(70) suggest the use-
fulness of cognitive behavioural or (less frequently) systemic group-based interventions of various kinds for mentally disordered offenders. These include: seven studies of problem-solving skills training, ﬁ  ve studies of anger/aggression management, and three 
studies aimed at social skills problems. Three studies of problem-solving training reported no statistically signiﬁ  cant positive effects,

studies aimed at social skills problems. Three studies of problem-solving training reported no statistically signiﬁ  cant positive effects, 
while a further three reported some positive results with measures of outcome closely linked to the intervention. Anger management studies were predominantly negative with no statistically signiﬁ  -
cant positive effects reported by the majority of studies and positive results reported only with quite reactive measures or within quasi-experimental studies. Social skills interventions also enjoyed mixed success with either no statistically signiﬁ  cant positive effects being 
reported or positive effects observed only with reactive measures 
or in uncontrolled studies. While it is not possible to claim that psychotherapy is effective in addressing problems associated with ASPD, there is sufﬁ  cient preliminary data to justify further 
inquiry and to counter the therapeutic nihilism that usually per-vades this ﬁ  eld.

Psychotherapy for other personality disorders
Individuals with paranoid PD  are highly suspicious of other 
people, including doctors, and are often unable to acknowledge their own negative feelings towards others. This fact alone means that treatment is problematic, but given that other characteristics include concern that other people have hidden motives, expecta-tion of being exploited by others, inability to collaborate, social isolation, emotional detachment, and overt hostility, treatment becomes nearly impossible. This constellation of characteristics means research on this group of patients is very difﬁ  cult to con-
duct, since researchers are inevitably seen as having hidden motives. Whatever treatment method is employed, the ﬁ  rst step is the devel-
opment of a moderately trusting relationship. There is no research speciﬁ  cally investigating the outcome of psychotherapeutic treat-

ment for paranoid personality disorder. However, a number of studies have included patients with paranoid PD in assessment of 
treatment. In general, the presence of paranoid PD diminishes the 
effectiveness of psychotherapeutic treatment for other co-occurring personality disorders.
Most of the interest in schizotypal  personality disorder (STPD) 
has been in its relationship to schizophrenia, and hence there is lit-tle data on outcome of treatment using psychosocial methods. The Chestnut Lodge follow-up study yielded some data suggesting that patients who had schizophrenia plus STPD and had been treated within the psychotherapeutic milieu did slightly better than patients without STPD.
(75) This unexpected finding has not been 
explained.
Winston et al.(76) treated 32 patients with a range of personality

Winston et al.(76) treated 32 patients with a range of personality 
disorders, predominantly in DSM-III-R cluster C, using two forms of brief psychodynamic therapy (short-term dynamic psychotherapy or brief adaptational therapy) with 40 weekly sessions and waiting- list control. Because of ethical constraints, waiting-list subjects began 
treatment after 15 weeks. Although both therapies used psychody-namic techniques, brief adaptational therapy employed more cog-nitive strategies. Contrasted to waiting-list controls, treated patients showed moderate improvements in symptoms and target com-plaints at post-therapy. Though there were few between-treatment differences, there was more variance in outcome for the patients treated with short-term dynamic therapy, suggesting that 
for some patients the technique was unhelpful. Gains appeared to

for some patients the technique was unhelpful. Gains appeared to 
be maintained at 18-month follow-up. A larger trial of these thera-pies with mainly cluster C disorder
(77) led to similar ﬁ  ndings.
Effectiveness
It is difﬁ  cult to reach deﬁ  nitive conclusions about the effectiveness 
of psychotherapy in the treatment of personality disorders, chieﬂ  y 
because RCTs of psychological treatments for PDs are relatively scarce. There is evidence that personality disorders impact nega-tively on treatments for Axis I presentations. However, the strength and speciﬁ  city of this evidence varies both across Axis I diagnoses 
and also across personality disorders.
Historically, studies of psychotherapy for personality disorder

Historically, studies of psychotherapy for personality disorder 
have focused on cluster B PDs. Borderline personality disorder is the best studied of the PD diagnoses both from a biological and a psychotherapeutic perspective. The recent growth in the evidence base indicates the feasibility of coherent research programmes with a patient group usually seen as presenting substantial problems of 
engagement. Evidence from randomized trials suggests that struc-
tured treatments employing DBT or a psychodynamic approach are more effective than routine care. Data gathered so far support the use of both behavioural and psychodynamic interventions, while evidence for more short-term cognitive interventions is somewhat equivocal. Since most studies present data from open tr ials

or case-series, only two approaches can be considered ‘evidence-based’ . The available randomized trials of DBT and psychodynamic treatment are methodologically sound but limited in the latter case by relatively small sample sizes; further, both sets of studies were conducted in the context of clear leadership from the devel-opers. Because, for the most part, contrast was to routine care, it is difﬁ cult to ascertain whether outcomes are due to the structured 
nature of the programmes or their therapeutic orientation.
In relation to antisocial personality disorder, research into treat-
ments has been centred on patients seeking help for substance abuse or individuals seen within the penal system for problems associated with ASPD. There is no clear evidence of treatment efﬁ cacy for any one form of intervention. Conclusions in relation

to ASPD are limited not only by the small number of trials but also by the methodological limitations of these studies, particularly reactive measures of outcome and complex multifaceted inter-ventions (such as therapeutic communities) where effective transportable components of the treatment package are impossible to disaggregate.
Avoidant personality disorder has received only a modest amount 
of research attention. Individuals presenting with APD would nor-mally be offered social skills training or cognitive (exposure-based) 
techniques which are likely to be successful, but the generalization 
of improvements to other social contexts has not yet been well demonstrated.

899
Implications for clinical practice
With the exception of cluster B disorders, many individuals with 
PDs present to services for help with Axis I disorders. Clinicians should be aware that while treatments normally recommended for these problems can still work, they may do so to a lesser extent than would be expected if comorbid PD were not part of the clinical problem. However, they should not assume that this will deﬁ  nitely 
be the case. The situation is somewhat different in the case of the so-called dramatic PDs. Many of the features of the behaviour of 
individuals with borderline or antisocial PD create such distress for 
the people around them that clinicians tend to privilege these fea-tures over symptomatic states related to comorbid Axis I disorders when setting goals for treatment.
There is little doubt that psychological therapies have a place in

There is little doubt that psychological therapies have a place in 
the management of personality disorders, but the methodological shortcomings of the studies so far conducted limit our ability to make practical recommendations. Given the nature of the problem (supposedly enduring problems of character) the fact that few trials conduct follow-up over a longer period or include a contrast 
or control group over follow-up is a grave limitation of the data-

base. Only two studies (Chiesa’s 72 months follow-up and the MBT 5-year follow-up) have demonstrated that post-treatment differ-ences are maintained for extended periods. Clinical experience, somewhat contradicted by recent follow-along data, suggests that many individuals may show periods of complete remission fol-lowed by episodes of great severity, and therefore it is crucial to investigate the impact of treatment on this often chronic and cyclic course. DBT has good evidence for its immediate impact on behavioural problems of impulsivity and suicidality, but the evidence for long-term beneﬁ  t without further treatment is less

clear. Psychodynamic approaches aim to change the way the person thinks, and there is some evidence that this approach has some impact on mood states and interpersonal functioning. However, this emphasis on cognitive change requires longer term therapy, with some indication of slower rates of change but perhaps also more sustained gains over follow-up. While shorter interventions are likely to have lower immediate costs, longer ones would be justiﬁ  ed if they were more cost-effective in terms of service utiliza-
tion and other cost-offsets. However, evidence for these kinds of effects is scarce.
Debate about particular forms of therapy may be less relevant 
than attention to nonspeciﬁ  c factors, especially in the treatment

than attention to nonspeciﬁ  c factors, especially in the treatment 
of individuals with cluster B PDs. We have seen that successful approaches usually emphasize the importance of structure, a coherent theoretical base, a higher intensity of treatment than for many Axis I disorders, and especially, attention to the unique set of problems presented by the individual, with a clear psychological formulation guiding treatment. Decisions about which treatment to opt for might be best made with regard to pragmatic consider-ations rather than argument about which particular course is ‘best’ . It may even be better to offer patients intensive treatment initially and to follow with short bursts of treatment over a long period of time. The competence and training of senior clinicians who can offer supervision will be especially important, as will the skill mix of staff and the resources (including stafﬁ  ng level) available to the

service. These ‘nonspeciﬁ  c’ issues may be especially pertinent when 
considering the performance of evidence-based treatments in routine practice. Since systemic factors may be as relevant to success as the type of treatment offered, pragmatic trials would be 
useful to give an indication of the conditions required to imple-ment evidence-based therapies in routine services.
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4.12.7 Management of 
The treatment of personality disorders is a complex but rapidly 
evolving subject. It is to some extent described elsewhere in Chapters 3.3, 4.12.6, 4.13.1, 5.2.9, 6.3.5, 6.3.9 8.5.6, 9.2.4, 11.3.2, 11.16, and 11.17, and so this chapter excludes a full discussion of psychodynamic interventions, therapeutic communities, interven-tions for older people and the management of both adolescent and adult offenders.`
Methodological difﬁ  culties in evaluating 
the efﬁ  cacy of treatment
The requirements for establishing whether a treatment is effective

The requirements for establishing whether a treatment is effective 
for personality disorders are much more exacting than those for mental state disorders. These can usefully be described under four headings:
X duration of treatment
X comorbidity
X adherence to treatment
X outcome measures.
(a) Duration of treatment
For most mental state disorders it is relatively easy to choose the period over which efﬁ  cacy has to be demonstrated. In conditions 
that develop suddenly (e.g. panic), treatment trials could be for a very short time indeed. For others, particularly when maintenance treatment is being evaluated, at least 6 months may be necessary to establish continued efﬁ  cacy. In the case of personality disorders, it 
has been thought that efﬁ  cacy of treatment could not be judged

has been thought that efﬁ  cacy of treatment could not be judged 
adequately without at least a 2 to 3 year treatment phase. Personality disorder was regarded as being unlikely to change in the short-term. However, these ideas are changing in the light of evidence from longer-term follow-up studies of patients with personality disorder that show that these conditions do change over time in a consistent and predictable manner with substantial numbers of patients achieving full remission in the longer term.
(1) If these 
longer-term follow-up studies are replicated, it would suggest that therapy should aim to accelerate the process of recovery. Determining what constitutes an adequate amount of therapy and over what length of time is an empirical question. More recent studies have offered treatment over 1 year with a 1 year follow-up 4.12.7 management of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 902
to examine maintenance of effect(2,3) but other studies have chosen 
lengthier treatment phases of up to 3 years(4) with some reporting 
continued therapy in the follow-up phase which does not allow the effect of maintenance of the original effect to be judged.
(5) More 
recent studies, examining the effect of psychological treatments, have included a 1 year follow-up. The purpose of this follow-up period is to determine if treatment effects are maintained following the termination of treatment. Such a requirement is not a purist position; if a treatment for personality disorder appears to be effec-tive over a shorter period, this may be due to change in a concur-rent (comorbid) condition. In addition, if a treatment is to be judged efﬁ  cacious in personality disorder its effects should be last-
ing beyond the active treatment component.
(b) Comorbidity
Comorbidity has been deﬁ  ned as ‘the presence of any distinct

Comorbidity has been deﬁ  ned as ‘the presence of any distinct 
clinical entity that has existed or that may occur during the clinical course of a patient who has the index disease under study’ .
(5) The 
key word here is ‘distinct’ . True comorbidity implies the presence of two completely separate disorders in the same person which are not causally related to each other in any way. Co-occurrence ranges from true comorbidity to the presence of the same disorder in two or more different forms.
(6)
Comorbidity is the norm for most personality disorders both 
with other personality disorders or with mental state disorders. Borderline personality disorder is a major offender in this regard. Only about 1 in 20 of such disorders constitutes the pure condition,
(7) and multiple comorbidity with four or more disor-
ders is common.
In deciding on the efﬁ  cacy of any treatment for personality dis-

order it is impossible to be certain whether observed improvement is in the personality disorder or in a comorbid condition. This problem is made worse because personality assessment is allegedly confounded, or ‘contaminated’ , by the effect of a concurrent mental state disorder. Thus personality status apparently changes during the presence of a mental state disorder such as depression, only to return to the baseline normal subsequently.
(8,9) Apparent 
improvement in a personality disorder following a treatment may be entirely due to improvement in a concurrent mental state disorder. However, this conclusion does not mean that personality 
function , as opposed to personality disorder , does not change. The

function , as opposed to personality disorder , does not change. The 
underlying personality may remain stable, but if the setting and circumstances change, and this includes mental state changes, there can be marked changes in adjustment and so the manifestation of 
disorder will also change.
(10)
In view of these problems, a treatment for a personality disorder 
should ideally be tested in those patients who have that personality disorder only. As these patients are uncommon and atypical, it is difﬁ cult to interpret the data from clinical trials.
(c) Adherence to treatment
People with personality disorders do not usually form good rela-

tionships with therapists. Although this is in keeping with their problems with relationships elsewhere, it can be a major problem in any form of therapy. The problem is particularly marked with psychotherapy, in which long-held views are challenged by the therapist. The consequence is that many patients dropout of care, and sometimes no amount of therapeutic skill can maintainthem in care.
(11) The failure to maintain prescribed treatment,in whatever form, is a constant handicap in accumulating an evi-

dence base for interventions in personality disorder. Even within personality disorder there are differences between sub-groups. Most therapeutic trials have been inpatients with borderline per-sonality disorder while those with schizoid, paranoid, histrionic, narcissistic, and antisocial personality disorders appear much less frequently. This is probably related to treatment attitudes. Borderline, anxious, and avoidant personality disorders contain a much higher proportion of treatment seeking (Type S) personality disorders as opposed to treatment resisting (Type R) ones, which are most prominent in those with antisocial, schizoid, and para-noid personalities.
(12)
Any study of personality disorder is likely to have a large propor-

(12)
tion of dropouts and this complicates the interpretation of the effects of treatment. The exception is when patients are treated in restricted settings such as prisons and other closed facilities,
(13) but 
as these circumstances are abnormal it is difﬁ  cult to generalize 
from them.
(d) Outcome measures
The choice of outcome measures is a problem in the assessment of all psychiatric disorders, but difﬁ  culty is particularly great in

studies of personality disorders. These disorders affect both the individual and society, and a range of outcomes can be measured to cover these possibilities. Forensic psychiatrists and the general pub-lic usually consider that the outcome of mentally disordered offenders is best measured by the frequency of reoffending. This is an easily measured and reliable statistic, but it does not necessarily record symptomatic or personality change, and may be distorted by a range of other factors (e.g. patients who spend a long time in hospital or prison are not likely to reoffend). Changes in symptoms also have limited use since they may be a consequence of changes in mental state disorders quite independent of personality. Repeated measures of personality status also have disadvantages since, as noted earlier, they may be affected by changes with concurrent mental state disorder. Personality also changes with ageing irrespective of treatment.
(14)

(14)
Because of these difﬁ  culties, global outcome measures are often 
used to determine the degree of improvement in personality disorders in long-term follow-up studies, although a battery of measurements is normally used in short-term treatment studies. Unfortunately, there is no standardized set of measures of global outcome. It is reasonable to take into account symptomatic change, social functioning, quality of life, incidents of societal conﬂ  ict (e.g. 
police contacts), and reports from informants. Even these may not correctly reﬂ  ect change in personality status. Thus a person whose 
personality disorder does not change in any basic way may ﬁ  nd an 
environmental niche in which the personality disturbance does not manifest itself as conﬂ  ict. Such a person would show improvement 
on all the items listed above, but the improvement would be a con-sequence of environmental change, not of personality alteration.
(e) Minimum requirements for establishment of efﬁ  cacy

The evidence base for effectiveness of treatment in personality 
disorders is also exacting:
1 The treatment should be effective when used in the pure form 
of the personality disorder (in an explanatory trial) and subse-quently in other forms of the disorder in which comorbidity is more common (pragmatic trial).

903
2 Efﬁ  cacy cannot be established satisfactorily unless the treatment 
is tested in a randomized controlled trial.
3 A suitable control treatment or management needs to be tested 
against the experimental treatment.
4 Efﬁ  cacy should only be determined after a period of at least 
1 year because of the long duration of personality disorder. More 
recent randomized controlled trials in borderline personality disorder examining psychological therapies have met these more demanding criteria.
(15,16)
Dynamic psychotherapy
This is discussed in chapter 4.12.6.
Cognitive therapies
(a) Cognitive analytical therapy
Cognitive analytical therapy combines cognitive and analytical approaches and has been applied to the treatment of personality disorders, particularly the borderline group.
(17) The clinical mani-

festations of this condition are postulated to be a set of partially dissociated ‘self-states’ which account for the clinical features of this disorder. Such patients typically describe rapid switching from one state of mind to another, experiencing intense uncontrollable emotions or alternatively feeling muddled, or emotionally cut-off. Such ‘dissociative states’ (different from the conditions of similar name formerly linked to hysteria) are said to be activated by severe external threats and to be maintained by repetitions of threat and reinforcement by memories or situations which are similar to the original source of threat.
Cognitive analytical therapy is concerned with the identiﬁ  cation

Cognitive analytical therapy is concerned with the identiﬁ  cation 
of these different self-states and helping patients to identify ‘reciprocal role procedures’ , or patterns of relationships which 
are learned in early childhood and are relatively resistant to 
change.
(18) The patient is taught to observe and try to change 
damaging patterns of thinking and behaviour which relate to these self-states and to become more self-aware. The therapist’s role is to gather information about the patient’s experience of relationships and the different states he or she experiences, including interpreta-tion where necessary. Although the standard measure of evidence of effectiveness, the randomized controlled trial, has still not yet been reported for this treatment it has gathered an impressive group of adherents and has become widely used and now has a good theoretical and pragmatic base.
(18)

(18)
In its original form, cognitive therapy for depression was used to help the patient to identify and modify dysfunctional thoughts and beliefs through the use of speciﬁ  c cognitive techniques such as 
Socratic questioning. The focus of therapy was here and now the aim was to return the patient to his or her usual functioning by relieving current symptoms. The cognitive model of personality disorder does emphasize cognitive, emotional, and behavioural factors but the origins of personality problems are regarded as originating in the temperament of the child, childhood develop-ment, and experiences. Early infant attachment patterns, the child’s internal working model of relationships, self-identity, self-worth, and the emotional availability of the infant’s caregivers are central to how the child develops and these shape the adult self-identity, interpersonal relationships in adulthood, and behavioural and 
emotional coping responses.
(19)

(19)
One of the ﬁ  rst tasks of cognitive therapy in personality disor-
ders is to gain an historical account of the patient’s childhood development and background from which the therapist can derive a cognitive formulation linking past difﬁ  culties and presenting 
problems. Through the formulation, and understanding of the patient’s view of self and others, unique core beliefs are identiﬁ  ed

that are linked to affect and to overdeveloped behavioural patterns that prevent the individual from functioning in an adaptive manner, particularly in interpersonal contexts. Therapy focuses on beliefs that concern core concepts about the self and others that have developed from childhood onwards and associated behav-iours that have developed as coping strategies. The content and meaning of the beliefs have had an impact on past and present rela-tionships and are likely to impact the therapeutic relationship. These beliefs, formed through negative, possibly abusive and neglectful experiences with others, are likely to have resulted in low self-esteem, hypersensitivity to criticism, and poor relationships with peers, caregivers and others in adolescence. Once a clear understanding of the content of patient’s core beliefs and associated overdeveloped or compensatory behavioural patterns has been established, patients are encouraged to test out their beliefs and assumptions about others

of patient’s core beliefs and associated overdeveloped or compensatory behavioural patterns has been established, patients are encouraged to test out their beliefs and assumptions about others by learning new, more adaptive strategies for relating to others and to themselves. In borderline

personality disorder, typically patients hold beliefs such as ‘I am a 
bad and inadequate person’ and ‘others will abandon or reject me’ . Having formed these beliefs through experiences in childhood, borderline patients, for example, may have learnt to avoid close relationships, are highly sensitized to signs of disapproval in others and have developed a punitive, self-critical style of thinking and behaviour, including self-harm. The emphasis in cognitive therapy is in developing new ways of thinking about self and others and in testing out new ways of behaving that are less self-defeating and more likely to improve the patient’s interpersonal skills.
(19) In com-

parison with the treatment of Axis I disorders, cognitive therapy with personality-disordered individuals takes more sessions and spans a longer time because the underlying problems are more pervasive and ingrained. There are other important elements of cognitive and related therapies, of which schema therapy and dialectical behaviour therapy are the most prominent. One of these differences is on the emphasis and attention paid to the therapeutic relationship. In cognitive therapy for personality disorder, more emphasis is placed on establishing and maintaining a therapeutic alliance, as interpersonal difﬁ  culties which occur in the patient’s 
life outside therapy are also likely to arise within therapy. This is based on the hypothesis that the patient’s core beliefs are consistent across a wide range of settings and therefore are also likely to be 
manifest in therapeutic relationships. Patients are therefore likely

manifest in therapeutic relationships. Patients are therefore likely 
to be highly sensitive to signs of criticism and approval in their therapists. The models of treatment for personality disorder proposed by Beck and Freeman,
(20) Davidson,(19) Y oung,(21) and 
Linehan(22) have in common an attempt to integrate biological 
and psychosocial factors. All models of treatment recognize the importance of building a secure therapeutic relationship and transference and countertransference issues in therapy areincreasingly recognized as important mediators of the therapeutic process. These therapies utilize cognitive techniques to repair breakdown in communication that can occur during therapy. 4.12.7 management of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 904
Cognitive analytical therapy(18) also gives special attention to this 
aspect of therapy.
One of the goals of cognitive therapy with personality-disordered 
patients is to take advantage of these interpersonal difﬁ  culties in 
treatment by identifying and modifying the beliefs underlying them and, by extension, other relationships. Although people with personality disorders can recognize difﬁ  culties, they experience the 
problems as egosyntonic
(23) (i.e. accepted as normal because they 
are an intrinsic part of usual functioning). As a result, alternative and potentially more adaptive beliefs about the self and others need to be identiﬁ  ed and evaluated to see if they are indeed more

adaptive and embraced as a consequence. These alternative more adaptive beliefs require to be systematically reviewed and reinforced, and new behaviours and ways of relating to others need to be practiced repeatedly if changes are to be consolidated. T o achieve these changes, the therapist usually has to adopt a more directive approach than in cognitive therapy for depression and other Axis I disorders, and throughout will be more concerned with identifying and overcoming cognitive, emotional, and behav-ioural avoidance which maintains core beliefs.
(c) Other related psychological therapies
(i) STEPPS
Systems Training for Emotional Predictability and Problem Solving (STEPPS) is afﬁ  liated to the other cognitive psychotherapies. It was

(i) STEPPS
Systems Training for Emotional Predictability and Problem Solving (STEPPS) is afﬁ  liated to the other cognitive psychotherapies. It was 
developed by Nancee Blum in Iowa and has been extended across several states within the United States and to the Netherlands. It has some of the elements of standard cognitive behaviour therapy and dialectical behaviour therapy and is a manualized programme involving 20 2 h weekly group meetings; with speciﬁ  c 
goals (or lessons) identiﬁ  ed for each session.
(24) A randomized 
controlled trial has just been completed and this shows signiﬁ  cant 
gains in some areas compared with treatment as usual (Black, 2007, APA meeting, San Diego, USA).
(ii) Schema-focused therapy
Schema-focused therapy(21) is now becoming increasingly used in

Schema-focused therapy(21) is now becoming increasingly used in 
the treatment of borderline and antisocial personality disorders. It is a compendium of cognitive behaviour therapy, object relations theory, and gestalt therapy, and also involving what Y oung calls ‘limited reparenting’ . It is given in a relatively intensive form—two to three sessions a week for 1–2 years—but has been shown to be both more effective and cost-effective than transference-focused psychotherapy in a trial of treatments for borderline personality disorder.
(28)
(iii) Dialectical behaviour therapy

(28)
The era of evidence-based therapy in personality disorder began with a formal trial of dialectical behaviour therapy, a form of cog-nitive behaviour therapy linked to skills training and detached acceptance (or mindfulness), was compared with treatment as usual in a group of repeatedly self-harming female patients with border-line personality disorder.
(28,69)  The hypothesis that dialectical
behaviour therapy was effective in reducing self-harm was supported. Now several other randomized trials have taken place that show 
that DBT is particularly effective in reducing self-harm
(4,29,30)  though 
in another study, DBT improved hopelessness, depression, anger, and 
suicidal ideation but showed no difference in suicide attempts.(31)
This treatment has also been used systematically in the treatment 
of borderline personality disorder and those with comorbidsubstance abuse.(30) According to Linehan,(22) borderline personal-

ity disorder is primarily a dysfunction of emotional regulation which is assumed to have resulted from biological irregularities combined with certain dysfunctional environments. Others in con-tact with the patient are postulated as reinforcing this dysfunction by discounting or, in Linehan’s preferred term, ‘invalidating’ their emotional experiences. Borderline patients are emotionally vulner-able and have difﬁ  culty in regulating patterns of responses associat-

ed with emotional states. The maladaptive behaviours which form part of the borderline syndrome can be viewed as either the product of emotional dysregulation or as attempts by the individual at regu-lating intense emotional states by maladaptive problem-solving strategies. Dialectical behaviour therapy, as its name suggests, con-tains within it the notion of opposites; common themes that emerge in therapy with borderline patients, such as acceptance of things as they are (so that there is no need for suicidal action), and change (from former maladaptive types of response) may appear incom-
patible but are synthesized in the therapy.
The essentials of dialectical behaviour therapy
(22) are manual-

ized weekly individual psychotherapy, group psychoeducational behavioural skills training, and telephone consultation when con-sidered necessary. Therefore the content comprises a variety of problem-solving techniques including teaching the patient skills to help regulate emotions and tolerate distress, methods for vali-dating the patient’s perceptions, and behavioural and psychological versions of meditation skills. Therapists are also trained in case management. ‘Core mindfulness skills’ are also part of the treat-ment and involve teaching the patient to observe, describe, and take part in events and responses to events without dissociating from what is happening. The treatment encourages patients to take a non-judgemental approach to events and interactions and to do what is effective in situations rather than what they may feel is the 
‘right’ thing to do.

Summary of cognitive therapies
The collective view of the effectiveness of cognitive and dialectical 
behaviour therapies is that they are undoubtedly effective Leichsenring and Leibing
(32) examined 25 studies (but very few 
randomized controlled trials) and found cognitive behaviour therapy to be effective (effect size 1.0) but with psychodynamic therapies the effect size was larger (1.46), but the authors empha-sized these results were preliminary and need updating. More randomized controlled trials have been carried out into treatments for personality disorder in the last 4 years than in the previous 50 years and further reviews are needed. T o date we only have good evidence of effectiveness for borderline personality disorder, but cognitive behaviour therapy has also been shown to be effective in a randomized trial of avoidant personality disorder.
(33)
Nidotherapy

(33)
Nidotherapy is ‘the collaborative systematic assessment and modi-ﬁ cation of the environment to minimize the impact of any form of 
mental disorder on the individual or on society’ .
(25) It was devel-
oped speciﬁ  cally for the care of patients with multiple personality 
and major psychiatric pathology and is particularly focused on Type R (treatment resisting personality disorders). It makes no attempt to treat the patient directly but instead attempts to change the environment so there is a better ﬁ  t between individual and

905
setting. It is normally carried out individually by a nidotherapist 
working independently from other clinical services.(26) It has been 
tested in a randomized trial in which the main gain was in cost savings as patients spent less time in hospital
(27) and has also 
been used for antisocial personality disorder for the reduction of aggression and improvement in social functioning (http://www.controlled-trials.com (ISRCTN96256106)).
Therapeutic community treatments
There has been some confusion regarding the term ‘therapeutic community’ . It can apply to any form of environment created for a speciﬁ  c treatment but was really introduced and deﬁ  ned in its 
modern context by Maxwell Jones
(34) who created a structure that 
ran completely counter to that of the traditional (authoritarian) mental hospital. This can be deﬁ  ned as a socially cohesive structure 
depending on intensive group treatme nts carried out by  its residents.

depending on intensive group treatme nts carried out by  its residents. 
This approach, the democratic therapeutic community, differs from other forms of more coercive communities linked to criminal justice in the United States, often used for substance abusers, which are called concept therapeutic communities.
(35,36) Therapeutic 
communities have very strong advocates and the complexity of the intervention makes it difﬁ  cult to create a suitable comparison 
group to act as a control for a randomized trial; to date no such trial has been carried out.
Drug treatment

Drugs are often used for treating personality disorders although it is important to note that none are licensed for the treatment of these conditions. As with other forms of treatment, borderline personality disorder constitutes the largest group in which drug treatment is being used and is therefore worth examining separately. The evidence base for drug treatment is growing and there are now sufﬁ cient randomized controlled trials to evaluate and for other 
studies to be ignored in this review.
Borderline personality disorder is one of the most heterogeneous of all groups within the personality classiﬁ  cation and includes

Borderline personality disorder is one of the most heterogeneous of all groups within the personality classiﬁ  cation and includes 
extensive comorbidity with other personality disorders as well as with mental state disorders, particularly mood and stress-related disorders. This hinders the interpretation of Table 4.12.7.1, noting the problems of evaluation referred to at the beginning of this 
Table 4.12.7 .1 Summary of randomized controlled trials of drugs in the treatment of personality disorder (borderline except where indicated)
Drug group Individual drug Size of trial— n (ref) Main outcome measures Results
Tricyclic antidepressants@Amitriptyline 61(37)Depression, aggression, global 
improvementAmitriptyline no better than 
placebo
Selective serotonin
reuptake inhibitors (SSRIs)Fluoxetine
Fluvoxamine (cross-over 
study)40(38)
38(39)Aggression depression,
Mood shifts, aggression, impulsivityFluoxetine superior to placebo

placebo
Positive effects of ﬂ  uvoxamine 
on mood only
Antipsychotic drugs (both ﬁ  rst 
and second generation)Haloperidol
Olanzapine (wide-dosage 
range)
Olanzapine (mean 5.3 mg)
Aripiprazole 15 mg/day*61(37) and 108(40)
40(41)
28(42)
52(43)Depression, hostility, impulsiveness
Aggression, depression, anxiety
‘Random effects regression 
modelling of panel data’
Hostility, anger, depression, 
self-harmHaloperidol effective in reducing 
depression and hostility in ﬁ  rst 
study but not in second
Signiﬁ  cant improvement in 
an unrecognized scale (Clinical 
Global Improvement-BPD) 
only
Alleged improvement 
on composite measure 
(unsatisfactory)
Signiﬁ  cant improvement in all 
measures and reduction in 
self-harm
(MAOIs)Phenelzine

only
self-harm
(MAOIs)Phenelzine 
(60 mg/day)108(40) Depression, hostility, impulsiveness, 
anxietyPhenelzine superior to 
haloperidol and placebo for 
anger and hostility
Mood stabilizers and 
anti-convulsantsCarbamazepine (7 mg/day)†
Sodium valproate 
(850 mg/day)*
Sodium valproate*
Lamotrigine*
Topiramate*20(44)
30(45)
91(46)
27(47)
56(48)Depression, hostility
Depression, aggression, hostility
Aggression
Self-rated anger
Anger
*Patients recruited by advertisement.
†Patients recruited as inpatients.
@A study involving mainly cluster C personality disorders compared the tricyclic antidepressant, dothiepin, with cognitive beha viour therapy and self-help over a 2-year period and showed

@A study involving mainly cluster C personality disorders compared the tricyclic antidepressant, dothiepin, with cognitive beha viour therapy and self-help over a 2-year period and showed 
signiﬁ  cantly better response to dothiepin(49) (but study not included as after 2 years there were many deviations from the original protocol.4.12.7 management of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 906
chapter. The studies are complex, yet the numbers are generally 
small, the period of treatment variable (8 weeks to 6 months), the dosage of drugs is usually ﬂ  exible, and the outcomes manifold (and 
so variable that it is almost impossible to combine the data system-atically). Positive publication bias and recruitment of volunteers by advertisement diminish the relationship between this patients group and those in clinical practice.
(i) Antidepressants

Tricyclic antidepressants do not appear to be effective in border-line personality disorder and, interestingly, do not help depressive symptoms preferentially, suggesting that there are subtle differ-ences between the despair and emptiness of the borderlinepersonality disorder and the anhedonia of depressive illnesses. Selective serotonin reuptake inhibitors (SSRIs), have been used in many trials (including some not cited here in which comparisons of inadequately small numbers have been made with psychologi-cal treatments) and provide some evidence of a positive effect on aggression and impulsiveness in antisocial personality disor-der.
(38) Monoamine oxidase inhibitors show reduction of anger 
and hostility in one trial but conventional risk management uggests that this treatment should only be used in exceptionalcircumstances.
(ii) Antipsychotic drugs

Although antipsychotic drugs have been tested in the treatment of borderline personality disorder more frequently than any other drug treatment, the results are equivocal. Haloperidol may be effec-tive
(37) in the short-term, however continuation studies do not 
show sustained improvement.(50) Olanzapine has been tested in 
three trials and, apart from showing consistent weight gain in all of these, has not shown any real evidence of beneﬁ  t for any of the
core symptoms of borderline personality disorder. The only trial showing substantial beneﬁ  t was carried out with aripiprazole in 
symptomatic volunteers
(43); as aripiprazole has a complex pharma-
cological proﬁ  le with 5-HT and dopamine agonist and antagonist 
actions this could represent a novel intervention and is worthy of replication.
(iii) Mood stabilizers

Borderline personality disorder is characterized by rapid swings in mood and emotional lability is a core feature. It is therefore not surprising that mood stabilizers have been used in its treatment. Again the results are equivocal and this subject urgently needs the beneﬁ  t of a large independent trial. The most impressive result has 
been shown with the anticonvulsant drug, topiramate, which reduces aggression and hostility
(48,51) but this finding needs 
replication. Lithium may also be effective in aggression but a satis-factory level of evidence is lacking.
Critique of drug treatment for borderline personality 
disorder
The evidence for the value of drug treatment has been inﬂ  uenced 
greatly by a guideline issued by the American Psychiatric Association in 2001.

disorder
(49) This was a bold attempt to give clear recommendations 
to clinicians desperate to ﬁ  nd a way through the fog of uncertainty 
with the abyss of suicide yawning on one side and iatrogenic poly-poly-pharmacy (the patients with this disorder are multiple consumers of prescribed drugs) on the other. There were four recommendations:1 psychotherapy—both psychoanalytic/psychodynamic therapy, 
and dialectical behaviour therapy ‘have been shown to have efﬁ cacy’
2 pharmacotherapy for ‘affective dysregulation symptoms’ 
should’be treated initially with a selective serotonin reuptake inhibitor or related antidepressant such as venlafaxine’
3 treatment of ‘impulsive-behavioural dyscontrol symptoms’ 
also suggests ‘SSRIs are the initial treatment of choice’
4 ‘low-dose neuroleptics are the treatment of choice for “cognitive-

perceptual” symptoms’ .
These were criticized heavily at the time for going far beyond the 
evidence
(52–54)  and for some treatments, notably cognitive behaviour 
therapy, neglecting available evidence,(53) and further data accrued 
over the ensuing years has reinforced these concerns.(15,28,55) The 
recommendations concerning drug treatments are particularly suspect. There is no evidence worthy of the name that justiﬁ  es the

recommendations concerning drug treatments are particularly suspect. There is no evidence worthy of the name that justiﬁ  es the 
sub-grouping of borderline personality disorder into ‘affective dyscontrol’ , ‘impulsive-behavioural dyscontrol’ , and ‘cognitive-perceptual’ categories and these appear to be entities created to justify the use of particular drugs rather than provide a valid sub-division of a complex disorder. The creation of these essentially pseudo-diagnoses allows general conclusions to be made that all the drug treatments are efﬁ  cacious and that ‘taken together, the results of 
these studies suggest that the choice of medication can be guided as much by tolerability and safety as by symptom presentation’ .
(56) On 
the evidence analysed dispassionately this conclusion applies equally well to placebo, whose tolerability and safety are unparalleled.
Flamboyant group (cluster B, not borderline)

(56) On 
The evidence for drug use in other cluster B disorders is very limited. There may be a limited role for the use of mood stabilizers in reducing anger in dissocial personality. Lithium was found to be effective
(57) and this action has been found in other settings,(58) but 
not reproduced in dissocial personality disorder. Carbamazepine has also been found to reduce impulsivity
(59) but this result requires 
Odd eccentric group (cluster A)
No placebo-controlled, explanatory trials in this group have been conducted and no pragmatic trials provide evidence for drugs that remain in use. A mistrust of treatment given by others limits research and is probably an intrinsic part of the condition.
Anxious fearful group (cluster C)

The diagnostic overlap between cluster C personality disorders and neurotic disorders makes drawing conclusion about drug treat-ment for this group difﬁ  cult. No clear explanatory trails have been 
conducted and the evidence of the effectiveness of antidepressants is confounded by the presence of neurotic disorder.
(60,61)
The management of borderline personality disorder can now be directed by a combination of the evidence and clinical judgement. It is clear from the randomized trials of both pharmacological and psychological treatment that an organized plan of care leads to improvement. This includes a consistent approach, a constancy of

907
personnel and adequate access to inpatient care during crisis situa-
tions. The cognitively based therapies are effective and pragmatic, providing a higher degree of input to ensure effectiveness. The intermittent addition of low-dose haloperidol or aripiprazole may assist with worsening impulsivity. A trial of topiramate for anger or SSRIs for impulsivity may also be of value. These need to be trialed for a speciﬁ  c period, 4 to 8 weeks, with a clear plan to review or 
stop if effectiveness is not clear or deteriorates over time. The risks of prescribing need to be carefully weighed against the potential beneﬁ  ts. Polypharmacy increases risk with no evidence of beneﬁ  t. 
It is ethically important to ensure all patients have the capacity to consent to treatment, particularly for unlicensed drug use. Because the treatment of personality disorder is among the most complex of complex interventions
(62) it is likely that several treatments,

(62) it is likely that several treatments, 
given in combination in a systematic way, are best suited to many of those who have more severe personality disorders.
The management of other personality disorders remains largely 
guided by clinical experience. The general principles of service organization remain the same, however decisions regarding psychotherapy and pharmacotherapy need to be tailored to indi-viduals with an expectation of building a body of patient-based evidence, as other evidence is weak. Regular review of a manage-ment plan minimizes the likelihood of harm from any one course of action or the neglect of the patient’s presentation.
Some management options can now be considered to have a 
negative risk: beneﬁ  t ratio. These include behaviour therapy alone, 
tricyclic antidepressant therapy, and monoamine oxidase therapy.
Organization of services for personality 
disorder
It is likely that the organization of care for those with personality

disorder
It is likely that the organization of care for those with personality 
disorder has a much greater part to play than any speciﬁ  c single 
treatment in the clinical success of management but it is also fair to add that this conclusion is not based on excellent evidence. What is, however, clear from the randomized trials of both pharmacological and psychological treatment is that an organized plan of care leads to great improvement in those with personality disorder irrespec-tive of the exact nature of the intervention.
Services for the management of person ality disorder can include 
the ‘sole practitioner’ model (a single therapist seeing the patient), the ‘divided function’ model (in which part of the patient’s care is taken over by specially trained staff whilst others look after other parts), and the ‘specialist team’ model (in which a speciﬁ  c personal-

ity disorder service takes on all aspects of care). The general 
conclusion is that the ‘divided function or specialist team model 
is probably best for reducing risk and improving outcomes’ .
(63) The 
general principles of management apply to all personality disorders although the consequences of ignoring them will be greater for the ﬂ amboyant cluster of personality disorders than for others.
(a) Consistency
One of the reasons why those with personality disorders create so 
many problems in therapy is that they are highly sensitive to per-
ceived criticism and are therefore able to detect any inconsistency in their treatment. Sometimes this is a way of deﬂ  ecting attention 
away from fundamental problems associated with the personality 
disorder, but they are nonetheless effective in creating a screen that prevents other issues from being addressed. Clearly the fewer the people involved in care, the less are the chances of creating incon-

sistency. Keeping the number of main workers to a small number, and maintaining good communication, is a sound goal.
(b) Constancy
It is helpful to avoid changes in staff as far as possible. This is of particular relevance in the treatment of borderline personality disorder in which changes in therapists often re-enact the problems of loss and despair that the patient experiences so commonly in relationships.
(c) Adequate inpatient support
Staff involved in hospital care often believe that people with personality disorders should be kept out of hospital. This belief is based on the observation that such people exploit the opportuni-ties offered by admission and create circumstances whereby it is difﬁ  cult to discharge them. Much of this is opinion and not

founded on evidence. Patients with comorbid mental state and personality disorders actually have better outcomes if they have a hospital-oriented programme of care than treatment in the com-munity, whereas the opposite is true in the absence of personality disorder.
(64) However, this work was carried out before speciﬁ  c 
services for personality disorder were set-up in England, the ﬁ  rst 
country in the world to create such services.(65) The initial pilot 
service has just been evaluated and the results are encouraging, but the problem remains that those who wish to seek treatment from these services comprise only a small proportion of the total who suffer.
(72)
Problems with comorbidity

(72)
Perhaps the most important error in management is failure to recognize personality disorder when other psychiatric disorders are more prominent and appear to be the only presenting problem. This is becoming recognized in the development of treatment protocols. This problem is encountered widely in the mental health services among people presenting to emergency psychiatric clin ics,
(73)
in services for the homeless mentally ill,(74) and among heavy users 
of psychiatric services(75) and those with multiple admissions.(68)
In all these settings, personality disorder is often not recognized early enough. This is to some extent understandable as the assessment of personality disorder is difﬁ  cult in, for example, a 
busy emergency clinic. Nevertheless, failure to achieve a predicted response is often due to an earlier failure to detect the presence of personality disorder.

Some years ago that most sceptical of academic psychiatrists, Michael Shepherd, in referring to the contents of a book entitled Recent Advances in Psychiatry  commented that the content was 
more accurately deﬁ  ned as ‘recent activities’ , as ‘advances’ was too 
generous a word. Whilst not going quite as far as this in regard to advances in the treatment of personality disorder it is fair to add that the promise of effective therapies across the spectrum of personality dysfunction remains a long way off and we must be very careful not to oversell the evidence. The complexity of person-ality disorders often requires complex intervention, however, until we are conﬁ  dent that single treatments are effective the arguments

for evaluating them in combination have to be very strong on theoretical grounds to justify the cost.4.12.7 management of personality disorder

SECTION 4  clinical syndromes of adult psychiatry 908
We are still at the stage in which explanatory trials (ones demon-
strating efﬁ  cacy under optimal conditions) are at least as necessary 
as pragmatic ones (demonstrating benefit in conditions of ordinary practice). These need to be carried out with adequate numbers of patients (at least 50 in each treatment arm rather than an artiﬁ  cially derived sample size to justify a small number) and 
with good independent assessments carried out by research workers who are masked as much as possible from disclosure of treatment. These requirements are exacting but can be achieved.
(67)
We also need better pragmatic trials of patients seen in ordinary mental health practice whose treatment and characteristics are both representative and from whom it is possible to generalize ﬁ ndings with conﬁ  dence. Currently there are very few studies that

satisfy this requirement; one recent study combining an educational intervention with problem-solving is an exception.
(68)
Despite the caution of these statements these are exciting times 
in the management of personality disorder. We are no longer listening to the once powerful lobby that claimed that patients with these conditions should not be treated by psychiatric services, or to the pessimists that still regard these conditions as untreatable. We are in the equivalent position as those in the early 1950s who suddenly became aware of the possibility that powerful treatments for severe mental illness were ready and waiting to be used. They do indeed appear to be within reach, but we must use them wisely.
The authors would like to thank Professor Peter Tyrer who co-authored the original chapter on which this is based.
Sampson, M., McCubbin, R., and Tyrer, P . (eds.) (2006). Personality disorder

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4.13
Habit and impulse 
control disorder
4.13.1 Impulse control disorders
Susan L. McElroy and Paul E. Keck, Jr.
This chapter ﬁ  rst deﬁ  nes impulse control disorders, and then 
summarizes available research on the clinical features, epidemiology, psychiatric comorbidity, family studies, psychobiology, and treat-ment response of the most common of these conditions (except for 
pathological gambling, which is reviewed in Chapter 4.13.2).
Deﬁ nitions of impulse control disorders
Historically, impulse control disorders have been broadly deﬁ  ned 
as harmful behaviours performed in response to irresistible impulses.
(1)In DSM-IV , an impulse control disorder is deﬁ  ned as 
the failure to resist an impulse, drive, or temptation to commit an act that is harmful to the individual or to others.
(2)DSM-IV also

(2)DSM-IV also 
stipulates that for most impulse control disorders, the individual feels an increasing sense of tension or arousal before committing the act and then experiences pleasure, gratiﬁ  cation, or relief at the 
time of committing the act. In the text describing these disorders, DSM-IV states that after the act, there may or may not be genuine regret, self-reproach, or guilt. In ICD-10,
(3) these conditions are 
classiﬁ  ed as habit and impulse disorders and deﬁ  ned as repeated 
acts that have no clear rational motivation, cannot be controlled, and that generally harm the patient’s own interests and those of other people. ICD-10 further states that the behaviour is associated with impulses to action.
In DSM-IV , impulse control disorders are listed in a residual

In DSM-IV , impulse control disorders are listed in a residual 
category, ‘Impulse control disorders not elsewhere classified’ , which includes intermittent explosive disorder (IED), kleptomania, pyromania, pathological gambling, trichotill16omania, and impulse 
control disorders not otherwise speciﬁ  ed (NOS). Examples of 
impulse control disorders NOS are compulsive buying disorder, repetitive self-mutilation, pathological skin picking, and onycho-
phagia (severe nail-biting).
(1) In ICD-10, habit and impulse 
disorders are also listed as a residual category. Similar to DSM-IV , it includes pathological gambling, pathological ﬁ  re-setting (pyro-
mania), pathological stealing (kleptomania), trichotillomania, other habit and impulse disorders (which includes IED), and habit and impulse disorder, unspeciﬁ  ed.
It should be noted that with mounting research, the impulse

It should be noted that with mounting research, the impulse 
control disorders are increasingly viewed as complex conditions sharing, in addition to irresistible impulses to perform harmful behaviours, features of trait impulsivity, trait compulsivity, and mood dysregulation, as well as obsessive compulsive mood, and addictive disorders.
(1)
Intermittent explosive disorder
Deﬁ nition and clinical features
Intermittent explosive disorder (IED) is deﬁ  ned in DSM-IV as

(1)
Intermittent explosive disorder (IED) is deﬁ  ned in DSM-IV as 
several discrete episodes of failure to resist aggressive impulses that result in serious assaultive acts or destruction of property (criterion A). Also, the degree of aggression expressed during an episode is grossly out of proportion to any precipitating psychosocial stress-ors (criterion B) and the explosive episodes are not better account-ed for by another mental disorder or due to the direct physiological effects of a substance or a general medical condition (criterion C). Varying deﬁ  nitions of IED based on the DSM-IV criteria have 
been proposed and used.
(4,5) One important set of research criteria 
for IED, for example, allows for less severe aggressive episodes, such as recurrent verbal outbursts against others without physical aggression, but requires that the aggressive episodes be recurrent and associated with distress or dysfunction.

(4)Although ICD-10 
lists IED under ‘Other habit and impulse disorders’ , it does not provide speciﬁ  c criteria for its diagnosis.
Regarding phenomenology, persons with IED describe their 
aggressive episodes as explosive, uncontrollable, unpremeditated, and brief; often provoked by minor stimuli; and associated with various psychological and physical symptoms, especially changes in mood, awareness, and autonomic arousal.
(4,6) The frequency of Contents
 4.13.1 Impulse control disorders
 4.13.2 Special psychiatric problems relating to gambling

SECTION 4  clinical syndromes of adult psychiatry 912
episodes depends in part on how the disorder is deﬁ  ned. In the 
National Comorbidity Survey Replication (NCS-R), where the DSM-IV A criteria of ‘several’ episodes was operationalized to be three or more lifetime attacks, persons with IED had a mean of 43 lifetime attacks.
Many persons with IED describe problems with chronic or trait 
anger and frequent ‘subthreshold’ aggressive episodes in which they manage to resist enacting aggressive impulses or express them with less destructive behaviours (e.g. screaming rather than assault).
(4,6) These subthreshold episodes are similar to the anger 
attacks (sudden episodes of intense anger with autonomic arousal) often described in patients with mood (bipolar and depressive) disorders.
(7)
Of note, the relationship between IED speciﬁ  cally and impulsive

(7)
Of note, the relationship between IED speciﬁ  cally and impulsive 
aggression in general remains unclear and the two phrases are not necessarily synonymous. In particular, like other impulse control disorders, the aggression of IED usually involves elements of lack of control (e.g. compulsivity) and affect dysregulation (extreme anger, irritability and/or mood instability) as well as impulsivity. Thus, IED may be one form of impulsive aggression.
Epidemiology and course
Once thought to be rare, recent research has shown that IED is common in both clinical and general population samples. In the most rigorous study to date, the NCS-R, lifetime and 12-month prevalence estimates of DSM-IV IED in the general population were 7.3 per cent and 3.9 per cent, respectively.
(5) The lifetime and 
12-month prevalences of more narrowly deﬁ  ned IED (in which

12-month prevalences of more narrowly deﬁ  ned IED (in which 
three episodes in the same year were required for diagnosis) were 5.4 per cent and 3.5 per cent, respectively. The disorder is also likely to be common in forensic populations but data are not available.
IED is probably more common in males than females. In the 
NCS-R, 9.3 per cent of men versus 5.6 per cent of women met life-time DSM-IV criteria for the disorder. IED begins in childhood or adolescence; follows a chronic or episodic course; and is associated with distress, morbidity (e.g. injuries), and social and occupational impairment.
(4-6) For example, in the NCS-R, IED had a mean age 
of onset of 14 years, was persistent over the life course (with averages of 6.2–11.8 years with attacks), and was associated with substantial role impairment.
(5) However, the prevalence of the dis-
order was signiﬁ  cantly lower among persons 60 years and older 
(2.1 per cent).

Associated psychopathology and comorbidity
IED often co-occurs with other psychiatric disorders.(4–6) In the 
NCS-R, 81.8 per cent of respondents with lifetime DSM-IV IED met criteria for at least one other lifetime DSM-IV disorder. Speciﬁ  cally, IED was signiﬁ  cantly comorbid with all DSM-IV 
depressive, anxiety, and substance use disorders assessed after controlling for age, sex, and race. It was also signiﬁ  cantly comorbid 
with oppositional deﬁ  ant disorder, conduct disorder, and attention-
deﬁ cit/hyperactivity disorder.
Importantly, the boundaries between IED and other conditions 
characterized by episodic and/or impulsive aggression have not been clearly delineated. Indeed, the comorbidity between IED and both bipolar disorders and Axis II disorders was not assessed in the NCS-R.
(5) Comorbidity with Axis II disorders was not determined

(5) Comorbidity with Axis II disorders was not determined 
because the prevalence of these disorders was not evaluated. Comorbidity with bipolar disorders was not assessed because of 
how IED was deﬁ  ned; cases of IED with lifetime mania or hypoma-
nia were excluded from analysis (number not speciﬁ  ed) so that the 
prevalence of IED was not overestimated by cases of bipolar disor-der with anger attacks. Of note, although the relationships between IED and both bipolar and cluster B personality disorders remain unclear, clinical studies suggest that patients with IED have high rates of these conditions.
(4,6)
Family studies suggest that relatives of probands with IED have high rates of impulsive violent behaviour, substance abuse, and possibly mood and other impulse control disorders.
(4,6,8,9) In a 
family history study of patients with temper outbursts meeting the ﬁ rst two DSM-III criteria for IED, non-adopted patients were sig-

niﬁ cantly more likely than adopted patients to have a family history 
of temper outbursts.
(9) Of 25 subjects with DSM-IV IED evaluated 
via the family history method, 8 (32 per cent) of subjects had a ﬁ rst-degree relative with probable IED, 20 (80 per cent) had 
at least one ﬁ  rst-degree relative with a substance use disorder, 14 
(56 per cent) a mood disorder, and 14 (56 per cent) an impulse control disorder.
(6) A blinded, controlled family history study using 
broadly-deﬁ  ned IED criteria found a signiﬁ  cantly increased morbid 
risk of the condition in relatives of affected probands (26 per cent) compared with relatives of control probands (8 per cent).
(4)
Psychobiology
Persons with impulsive aggression have been consistently found to have abnormalities in serotonergic function.
(4)Although most

(4)
(4)Although most 
studies included subjects with impulsive aggression and personality disorders, a few included persons with IED or possible IED. Thus, in a study of 58 violent offenders and impulsive ﬁ  re-setters, 33 
(57 per cent) of whom had DSM-III IED, lower cerebrospinal ﬂ  uid 
(CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) were found in the impulsive offenders and ﬁ  re-setters than in the 
non-impulsive offenders and normal control subjects.
(10)
In a functional magnetic resonance imaging (MRI) study of 
response to social threat, 10 subjects with IED showed exaggerated amygdala reactivity and diminished orbitofrontal cortex activation to faces expressing anger compared with controls.
(11) The authors 
noted these ﬁ  ndings were similar to other disorders characterized

noted these ﬁ  ndings were similar to other disorders characterized 
by impulsive aggression, including borderline personality and bipolar disorders, and that they supported a link between a dys-
functional frontal-limbic network and aggression.
Treatment response
Clinical experience suggests that IED may be less responsive to 
insight-oriented and more responsive to cognitive behavioural therapies, particularly those stressing anger management.
(4,6,12) 
Medications reported effective in deﬁ  nite or probable IED, some 
in controlled trials, include antiepileptics (e.g. phenytoin, car-bamazepine, oxcarbazepine), antidepressants (e.g. tricyclics, serot-onin reuptake inhibitors), mood stabilizers (e.g. lithium, valproate), β-blockers, psychostimulants, and even antiandrogens. Mood 
stabilizer monotherapy and antidepressant augmentation of mood stabilizers have both been reported to successfully treat IED and/or anger attacks in patients with bipolar disorders.

(6,7)Antidepressants 
have been reported to be effective in anger attacks associated with

913
major depression.(12) Finally, serotonin reuptake inhibitors, mood 
stabilizers, antiepileptics, and antipsychotics may be effective for impulsive-aggressive behaviour in personality-disordered patients.
(13)
Kleptomania
Kleptomania is deﬁ  ned in DSM-IV as follows:
X recurrent failure to resist impulses to steal objects that are not 
needed for personal use or for their monetary value (criterion A);
X increasing sense of tension immediately before committing the 
theft (criterion B);
X pleasure, gratiﬁ  cation, or relief at the time of committing the 
theft (criterion C);
X the stealing is not committed to express anger or vengeance and 
is not in response to a delusion or a hallucination (criterion D);
X the stealing is not better accounted for by conduct disorder, a 
manic episode, or antisocial personality disorder (criterion E).
In ICD-10, kleptomania (or pathological stealing) is deﬁ  ned as

In ICD-10, kleptomania (or pathological stealing) is deﬁ  ned as 
the repeated failure to resist impulses to steal objects that are not acquired for personal use or monetary gain.
An increasing number of studies have systematically examined 
the phenomenology of groups of people with DSM-deﬁ  ned klep-
tomania.
(14–17) In these studies, most subjects described irresistible

tomania.
(14–17) In these studies, most subjects described irresistible 
impulses or urges to steal, tension with the impulses, and tension relief either during or shortly after the act of theft (as required by the DSM criteria). Many subjects described the impulses as sense-less, intrusive, uncomfortable, and uncontrollable. Many tried to resist the impulses with varying degrees of success. Some reported pleasurable feelings during the act of theft, often described as ‘a rush,’ ‘a high,’ or ‘a thrill.’ Most patients reported instances of impulsive stealing, but some also described premeditated stealing, the aim of which was sometimes to relieve the impulses to steal. Many sub-jects reported that they had lied to conceal their stealing. Some subjects developed rules for their stealing behaviour—for instance, stealing only from work or from certain types of shops (e.g. drug stores but not department stores), or stealing certain items but not

others (e.g. jewellery but not clothing). Many subjects considered 
their stealing to be wrong, and many, but not all, reported guilt or remorse after stealing. Subjects who had been arrested for shoplift-ing reported that it had varying effects on their symptoms—some stopped stealing completely, some stopped for a limited amount of time, while others reported that their stealing was unaffected. Some stated they continued to steal once incarcerated.
These studies have also found that some subjects with apparent 
kleptomania report varying degrees of amnesia surrounding the act of stealing.
(17) Many of these subjects deny impulses, tension, or 
relief with their thefts. Other subjects who are not amnesiac for their stealing episodes may also deny experiencing impulses, tension, relief, and/or pleasure. For these subjects, stealing appears to have become automatic or habit-like.
(17)

(17)
Kleptomania is presumed to be rare but its prevalence is unknown. Available studies suggest that only a small portion of shoplifters (from none to 8 per cent) represent true cases of kleptomania.
(14)
However, it has been argued that these rates may be spuriously 
low because psychiatric evaluations may not have always been suf-ﬁ ciently thorough, operational diagnostic criteria were rarely used, 
and kleptomania may have been under-represented in the samples due to selection bias (i.e. people with repeated apprehensions were more likely to be legally rather than psychiatrically referred). Also, kleptomania may be relatively common in clinical populations; it was the second most common lifetime impulse control disorder in a group of adult psychiatric inpatients assessed with a structured interview, present in 9.3 per cent of the sample.
(18)
Kleptomania is probably more common in women than in

(18)
Kleptomania is probably more common in women than in 
men.(14–17)Many cases begin in adolescence or early adulthood, 
and often follow an episodic or a chronic course.
Clinical studies show that kleptomania often co-occurs with other Axis I psychiatric disorders, including mood, anxiety, substance use, eating, and impulse control disorders.
(14–18) In the only con-
trolled study,(16)10 patients with kleptomania had signiﬁ  cantly 
higher rates of comorbid psychiatric disorders, particularly mood disorders, other impulse control disorders, and substance abuse or dependence (mainly nicotine dependence), than 29 psychiatric comparison patients and 60 patients with alcohol abuse or depen-dence. Several studies, including the one controlled study, found especially high rates of bipolar disorders.
(15–17)  Conversely, high 
rates of kleptomania have been found in women with eating disorders
(14) and patients with depressive disorders.(19)

Preliminary data suggest patients with kleptomania may also 
have high rates of certain Axis II disorders.(17) However, the rela-
tionship between kleptomania and antisocial personality disorder is not understood.
Uncontrolled studies suggest kleptomania may be associated with increased familial rates of mood, substance use, anxiety, and possibly impulse control disorders.
(17) For example, of 103 ﬁ  rst-
degree relatives of 20 patients with DSM-IIIR-deﬁ  ned kleptomania 
evaluated blindly by the family history method, 22 (21 per cent) had a major mood disorder, 21 (20 per cent) had a substance use disorder, and 13 (13 per cent) had an anxiety disorder, including seven (7 per cent) with obsessive compulsive disorder
(15) Also,

(15) Also, 
two (2 per cent) had apparent kleptomania. However, a controlled family study found similar rates of kleptomania in ﬁ  rst-degree 
relatives of probands with obsessive compulsive disorder and those of control probands.
(20)
Preliminary research suggests kleptomania may be associated with serotonergic and frontal lobe dysfunction. In one study, the num-ber of platelet serotonin transporters, evaluated via [3H] parox-etine binding, was lower in 20 patients with obsessive-compulsive related disorders, including ﬁ  ve patients with kleptomania, than in 
20 healthy control subjects.
(17) In another study, 10 females 
with DSM-IV kleptomania were more likely than controls to have decreased white matter microstructural integrity in inferior frontal brain regions when evaluated with diffusion tensor imaging.
(21)4.13.1 impulse control disorders

SECTION 4  clinical syndromes of adult psychiatry 914
Although no controlled psychological treatment studies of klepto-
mania have been published, various types of cognitive behavioural therapy may be effective.
(12,17) There are also successful reports of 
the use of psychodynamic psychotherapies, but there are negative reports as well.
(12,15)
Medical treatments with antidepressant, mood-stabilizing, or 
anxiolytic properties have been reported to be effective in klepto-mania, primarily in case reports and case series. These treatments include tricyclics, serotonin reuptake inhibitors, trazodone, lithium, 
valproate, electroconvulsive therapy, and benzodiazepines.
(12,15,17)
There are also reports of patients with kleptomania responding to 
the opioid antagonist naltrexone and the antiglutamatergic agent topiramate.
(12,17)
However, in the only controlled pharmacotherapy study of

(12,17)
However, in the only controlled pharmacotherapy study of 
kleptomania published to date, an open-label trial of escitalopram treatment in 24 subjects followed by double-blind discontinuation in 15 of 19 responders, there was no difference in response rate (deﬁ ned as greater than a 50 per cent decrease in theft episodes 
per week) between subjects receiving escitalopram (3 [43 per cent]) and those receiving placebo (4 [50 per cent]).
(22)
Pyromania
Pyromania is deﬁ  ned in DSM-IV as follows: deliberate and pur-
poseful ﬁ  re-setting on more than one occasion (criterion A) that is 
associated with tension or affective arousal before the act (criterion B), fascination with, interest in, curiosity about, or attraction to ﬁ re and its situational contexts (criterion C), and pleasure, gratiﬁ  -
cation, or relief when setting ﬁ  res, or when witnessing or partici-

pating in their aftermath (criterion D). Also, the ﬁ  re-setting is not 
done for monetary gain, as an expression of sociopolitical ideology, to conceal criminal activity, to express anger or vengeance, to improve one’s living circumstances, in response to a delusion or hallucination, or as a result of impaired judgement (criterion E), and is not better accounted for by conduct disorder, a manic episode, or antisocial personality disorder (criterion F). In ICD-10, pyromania (or pathological ﬁ  re-setting) is deﬁ  ned as multiple acts 
of, or attempts at, setting ﬁ  re to property or other objects, without 
apparent motive, and by a persistent preoccupation with subjects related to ﬁ  re and burning. The essential features are as follows:
X repeated ﬁ  re-setting without any obvious motive such as mone-
tary gain, revenge, or political extremism
X an intense interest in watching ﬁ  res burn

X reported feelings of increasing tension before the act, and intense 
excitement immediately after it has been carried out.
Although the authors were unable to locate any systematic 
reports of a group of people with pyromania by either of the above criteria sets, there are numerous case reports and case series of people with repetitive ﬁ  re-setting behaviour who would probably 
meet these criteria for pyromania. For example, in what is still probably the largest study of pathological ﬁ  re-setting, in 1951, 
Lewis and Y arnell
(23) evaluated 1 145 of 2 000 American case records 
of males 16 years of age and older from the National Board ofFire Underwriters (selection criteria were otherwise not clearly speciﬁ  ed). They concluded that 688 of these males were best classi-

ﬁ ed as ‘pyromaniacs’ as ‘they set ﬁ  res for no practical reason and 
received no material proﬁ  t from the act, their only motive being to 
obtain some sort of sensual satisfaction’ . Lewis and Y arnell did not provide quantitative data summarizing these 688 cases, but stated that 50 of the subjects ‘approached true pyromania’ , in that they were able to give a ‘classical description of the irresistible impulse’ . Speciﬁ  cally, before they set ﬁ  res, these subjects described ‘mounting 
tension; . . . restlessness; the urge for motion; . . . conversion symp-toms such as headaches, palpitations, ringing in the ears, and the gradual merging of their identity into a state of unreality’ .
The prevalence of pyromania is unknown.(19) Although there are

The prevalence of pyromania is unknown.(19) Although there are 
numerous studies of ﬁ  re-setting behaviour, few of these studies 
systematically assessed pyromania in their subjects. Those that did use variable deﬁ  nitions of pyromania and reported widely discrep-
ant rates. For example, in their 1951 study of 1 145 adult males with pathological ﬁ  re-setting, Lewis and Y arnell
(23) reported that 688 
(60 per cent) could be classiﬁ  ed as having broadly deﬁ  ned pyroma-
nia, but only 50 (4 per cent) as having the ‘true’ disorder.
Pyromania is probably more common in males than females and 
usually begins in adolescence or early adulthood.(19,23) How often 
childhood ﬁ  re-setting represents pyromania is unknown. Clinical 
descriptions indicate that the course of pyromania may be episodic or chronic, but its course into old age is unknown.

There are no studies of the psychiatric comorbidity of a group of people with well-defined pyromania. However, there are case reports of people with apparent pyromania who have comorbid mood, obsessive compulsive, eating, paraphilic, and possibly psy-chotic disorders.
(23) In addition, impulsive ﬁ  re-setters have been 
reported to have high rates of mood, substance use, and cluster B personality disorders, as well as suicide attempts.
(10)
There are no family history studies of pyromania, but studies of impulsive ﬁ  re-setters suggest elevated familial rates of substance 
use disorders.
(8)
Biological studies
There are no biological studies of pyromania, but studies of impulsive ﬁ  re-setters suggest they have abnormalities in central 
serotonergic neurotransmission.
(10)

(10)
There are no systematic treatment studies of pyromania.(12,19) 
There is one case of an 18-year-old male with DSM-IV pyromania and a chief complaint of ‘feeling addicted to setting fires’ who responded to the combination of topiramate and cognitive behaviour therapy.
(24) There is also a case report of two men in 
both of whom pyromania appeared to be part of a paraphilia and responded to antiandrogen medication.
(25)
Clinical reports on the treatment of pathological ﬁ  re-setting 
in general stress use of various psychological interventions (e.g. cognitive behavioural, psychoeducational, supportive, and insight-oriented) to address the ﬁ  re-setting behaviour, and appropriate

915
treatment of any comorbid psychiatric disorders. Preliminary 
data suggest combined psychosocial treatment approaches may be helpful in reducing further ﬁ  re-setting behaviour, at least in 
juveniles.
(19)
Trichotillomania
Trichotillomania is deﬁ  ned in DSM-IV as follows:
X recurrent pulling out of one’s hair resulting in noticeable hair 
loss
X an increasing sense of tension immediately before pulling out 
the hair or when attempting to resist the behaviour
X pleasure, gratiﬁ  cation, or relief when pulling out the hair
X the disturbance is not better accounted for by another mental 
disorder and is not due to a general medical condition (e.g. a dermatological condition)
X the disturbance causes clinically signiﬁ  cant distress or impair-
ment in social, occupational, or other important areas of functioning.
In ICD-10, trichotillomania is deﬁ  ned as noticeable hair-loss due

In ICD-10, trichotillomania is deﬁ  ned as noticeable hair-loss due 
to a recurrent failure to resist impulses to pull out hairs. ICD-10 further states the hair-pulling is usually preceded by mounting tension and is followed by a sense of relief or gratiﬁ  cation and that 
the diagnosis should not be made if there is a pre-existing inﬂ  am-
mation of the skin, or if the hair pulling is in response to a delusion or a hallucination.
Hair is most often pulled from the scalp but also from the eye-
lashes, eyebrows, face, axilla, arms, legs, abdomen, and pubis.
(26,27)
Extracted hair may be chewed or swallowed. Medical complica-tions include trichobezoars (hairballs that form in the stomach) and, uncommonly, obstruction or perforation of the stomach or bowel.
Some authorities have argued that both the DSM-IV and ICD-10

Some authorities have argued that both the DSM-IV and ICD-10 
criteria for trichotillomania are too narrow, noting that patients with distressing hair pulling behaviour, especially children, may not always experience impulses and/or tension before hair pulling or relief with or after hair pulling.
(26–28)  Indeed, for some persons, 
the hair pulling may be automatic or habit-like and not associated with urges, tension, or relief. In addition, the hair loss may not be noticeable. For this reason and because hair pulling is a self-grooming behaviour, some authorities have argued that trichotil-lomania should be grouped with other self-grooming behaviours that may become problematic (e.g. skin picking and nail biting, which are discussed later) into a family of grooming disorders or body-focused impulse control disorders.
(20,26,27)
The prevalence of DSM-IV or ICD-10 deﬁ  ned trichotillomania is

The prevalence of DSM-IV or ICD-10 deﬁ  ned trichotillomania is 
unknown, but survey studies suggest between 0.5 per cent—3.5 per cent of college students report problematic hair pulling.
(26,27)
Clinical studies indicate trichotillomania is more common in 
females than in males; may begin in childhood, adolescence, or adulthood; and may have an episodic or chronic course.
(26,27)
Spontaneous remissions may occur, particularly in children with recent onset of the disorder.Associated psychopathology and comorbidity
Trichotillomania often co-occurs with mood, anxiety, eating, substance use, and other impulse control disorders in clinical sam-ples of adults.
(26,27)It may also co-occur with various personality 
disorders, with histrionic, borderline, and obsessive compulsive commonly being cited.
(26,27) In paediatric samples, trichotillomania 
is similarly associated with mood, anxiety, and substance use disorders.
(26)
Family Studies

(26)
Preliminary family research suggests that trichotillomania may be associated with increased rates of obsessive-compulsive and groom-ing disorders among ﬁ  rst-degree relatives.
(26) A controlled family 
study of 22 probands with compulsive hair pulling, 17 (77 per cent) of whom met DSM-III-R criteria for trichotillomania, found that depression, alcoholism, drug abuse, obsessive compulsive disorder, and antisocial personality disorder were signiﬁ  cantly more frequent 
among the ﬁ  rst degree relatives of hair pullers than relatives of con-
trol probands.
(28) Conversely, another controlled family study 
found signiﬁ  cantly higher rates of grooming disorders (trichotil-

lomania as well as pathological skin picking, pathological nail bit-ing, and impulse control disorder NOS) in first-degree relatives of probands with obsessive compulsive disorder than in ﬁ rst-degree relatives of control probands.
(20)
Neuroimaging studies in subjects with trichotillomania have 
shown hyperactivity in the cerebellum and right superior parietal lobe as well as possible structural abnormalities of the left putamen, left inferior frontal gyrus, right cuneal cortex, and cerebellum.
(26,27,29)  Neuropsychological abnormalities found in 
trichotillomania patients have included increased error rates in spatial processing, divided attention, nonverbal memory, and executive functioning.
(26,29)
Genetic studies suggest trichotillomania may be associated with

(26,29)
Genetic studies suggest trichotillomania may be associated with 
sequence variants in the slit and trk-like 1 (SLITRK1) gene and the T10ZC polymorphism of the serotonin receptor 2A gene.
(30,31)
There are a few published reports of the successful treatment of trichotillomania with insight-oriented psychotherapies, but there are many successful reports with various behavioural-based thera-pies.
(12,26,27)  Indeed, to date, four randomized, controlled studies 
supporting the effectiveness of behavioural treatments in adult trichotillomania have been published. In these studies, habit rever-sal was more effective than negative practice training (N =34); CBT 
was more effective than clomipramine and placebo (N =16); behav-
iour therapy was superior to ﬂ  uoxetine and a wait-list control 
(N=43); and acceptance and commitment therapy plus habit rever-
sal was superior to wait-list control (N =25).
(12,26,27)  In addition,

(12,26,27)  In addition, 
one randomized, controlled trial found a cognitive behavioural therapy package of awareness training, stimulus control, and habit-reversal training was superior to minimal attention control in paediatric trichotillomania.
(27)
Although many case reports and open trials describe successful 
treatment of trichotillomania with various serotonin reuptake inhibitors, controlled studies have yielded mixed results.
(12,26,27)
Two small (N =13 and N =12) double-blind, crossover trials found 4.13.1 impulse control disorders

SECTION 4  clinical syndromes of adult psychiatry 916
clomipramine was superior to desipramine and equivalent to 
ﬂ uoxetine (which had beneﬁ  cial effects), respectively, in reducing 
hair-pulling symptoms. In contrast, 2 slightly larger (N =21 and 
N=23) placebo-controlled, double-blind crossover studies of ﬂ  uox-
etine (both up to 80 mg/day) in adult chronic hair pullers found ﬂ uoxetine was not superior to placebo in suppressing hair-pulling 
symptoms.
(12,26,27)In addition, as noted earlier, in the two con-
trolled comparisons which found cognitive behaviour therapy or behaviour therapy superior to clomipramine and ﬂ  uoxetine in 16 
and 43 patients with trichotillomania, respectively, neither drug was superior to placebo in reducing trichotillomanic symptoms.
(12)
Despite these negative studies, thymoleptics other than serotonin 
reuptake inhibitors have been reported to be effective for trichotil-lomania in case reports and case series. These include antidepress ants

such as imipramine, amitriptyline, isocarboxazid, trazodone, mianserin, and bupropion; the mood stabilizers lithium, olanzap-ine, and quetiapine; and various antimanic antipsychotics—used as either monotherapy or adjunctively with serotonin reuptake inhibitors.
Other medications described as being effective for trichotilloma-
nia, primarily in case reports or case series, are buspirone, fenﬂ  ura-
mine, topiramate, inositol, the progestin levonorgestrel, and naltrexone.
(12,26,27,32,33) Naltrexone was reported superior to 
placebo in one small controlled trial which has only been presented in abstract form.
(12) Case reports also describe the successful use of 
topical steroid ointments in combination with psychotropics when skin is irritated.
(12)
Compulsive buying disorder
History and clinical description

(12)
Although compulsive buying disorder (also called compulsive shopping, buying mania, and oniomania) is not classiﬁ  ed in DSM-
IV or ICD-10 as a mental disorder, diagnostic criteria have been proposed.
(34,35)  These include being frequently preoccupied with 
buying or subject to irresistible, intrusive, and/or senseless impulses to buy; frequently buying unneeded items or more than can be afforded; shopping for periods longer than intended; and experi-encing adverse consequences, such as marked distress, impaired social or occupational functioning, and/or ﬁ  nancial problems.
(35)
Persons with compulsive buying disorder often report irresistible

(35)
Persons with compulsive buying disorder often report irresistible 
or uncontrollable impulses to buy or shop; mounting tension or anxiety with the impulses; and relief of tension and/or pleasurable feelings (e.g. ‘a high’ , ‘a buzz’ , or ‘a rush’) with the act of buying or shopping. The disorder is associated with distress, ﬁ  nancial 
and legal difﬁ  culties, and impairment in social and vocational 
(34,35)
Compulsive buying behaviour is thought to be common, with an estimated lifetime prevalence of 5.8 per cent in the United States general adult population.
(36) Indeed, in a recent study of the preva-
lence of various impulse control disorders in a psychiatric inpatient population, compulsive buying disorder was the most common current (9.3 per cent) and lifetime (9.3 per cent) impulse control disorder diagnosis.
(18)
Compulsive buying disorder is probably more common in

(18)
Compulsive buying disorder is probably more common in 
women than men.(34,35) It may begin in adolescence or adulthood and usually has either an episodic or a chronic course. The course 
of compulsive buying disorder into old age is unknown.
Compulsive buying disorder often co-occurs with mood, anxiety, substance use, eating, and other impulse control disorders in clinical samples.
(34,35) It may also be associated with certain 
personality disorders, but this comorbidity has received less systematic attention.
(34)
Preliminary research, including one controlled study, suggests 
compulsive buying disorder is associated with increased familial rates of mood, substance use, and possibly impulse control disorders.
(34,35)
In a molecular genetic study, no association was found between two serotonin transporter gene polymorphisms and compulsive buying disorder.
(34)

(34,35)
(34)
Isolated reports of psychoanalytic and insight-oriented psycho-therapy in compulsive buying disorder have mostly been unsuc-cessful. Cognitive behavioural therapy may hold promise. Two patients with compulsive buying disorder each responding to cue exposure plus response prevention after failing clomipramine treatment have been described.
(12) In addition, a randomized study 
found group cognitive behavioural therapy (N =28) superior to 
wait-list control (N =11) in reducing compulsive buying episodes, 
time spent buying, and scores on buying symptom measures in 39 patients with compulsive buying disorder.
(37) Support groups pat-
terned after Alcoholics Anonymous, such as Debtors Anonymous, 
self-help books, and ﬁ  nancial counselling are available, but their

self-help books, and ﬁ  nancial counselling are available, but their 
effectiveness has not been formally evaluated.(12,34)
Various antidepressant medications have been reported to 
be effective for compulsive buying in case reports and open trials, but two randomized, placebo-controlled, double blind studies of ﬂ uvoxamine in a total of 54 patients with compulsive buying 
(N=17 and N =37, respectively) failed to show separation between 
drug and placebo.
(12,34)  Both studies, however, were limited by 
high placebo response rates, possibly due to the use of diaries to record buying behaviour. In a 7-week, open-label trial of citalopram (N=24) followed by a 9-week double-blind, placebo-controlled

high placebo response rates, possibly due to the use of diaries to record buying behaviour. In a 7-week, open-label trial of citalopram (N=24) followed by a 9-week double-blind, placebo-controlled 
continuation trial that omitted use of shopping diaries for the 15 subjects who met responder criteria, none of 7 patients randomized to remain on citalopram relapsed as compared with 5 (63 per cent) of 8 patients randomized to receive placebo (P=0.019)
(12,34) .
Patients with compulsive buying have also been reported to 
respond to mood stabilizers, naltrexone (at 100 mg/day but not 50 mg/day), and topiramate.
(12,34)
Repetitive self-mutilation
Repetitive self-mutilation, also called impulsive deliberate self-harm, parasuicide, or self-injurious behaviour, is the repeated,

917
direct destruction of body tissue without suicidal intent.(38,39)
Examples include skin cutting, skin burning, self-hitting, severe 
skin scratching, and even bone breaking. A wide range of body parts are mutilated, such as arms, legs, abdomen, head, chest, and genitals.
Numerous clinical studies suggest that this syndrome often 
meets the DSM-IV and ICD-10 deﬁ  nitions of impulse control 
(38) Speciﬁ  cally, repetitive self-mutilation is characterized 
by intrusive, recurrent, and irresistible impulses to harm oneself without suicidal intent that are associated with increasing tension, anxiety, anger, or other dysphoric affective states, along with relief of the uncomfortable affect with or shortly after the act of self-harm. In addition, the act of self-harm is often not associated with pain (i.e. associated with analgesia) and performed privately.
(38,39)
The prevalence of narrowly deﬁ  ned repetitive self-mutilation is

(38,39)
The prevalence of narrowly deﬁ  ned repetitive self-mutilation is 
unknown.(38,39) Clinical studies, however, suggest that the condi-
tion is more common in females than males, usually begins early in life (e.g. late childhood, adolescence, and early adulthood), and may persist for 10 to 15 years.
(38,39)
Repetitive self-mutilation often co-occurs with other Axis I and II psychiatric disorders.
(38,39) These include mood, substance use, 
eating, psychotic, dissociative, and borderline personality disorders. Repetitive self mutilation may also co-occur with suicide attempts and adverse childhood experiences in patients with certain pathologies, especially borderline personality disorder.
(39)
Of note, although deliberate self injury is a core feature of border-line personality disorder, not all patients with repetitive self mutila-tion have borderline personality disorder.
(38)
Family history

(38)
No family history studies of repetitive self-mutilation have been conducted.
Although studies have consistently found an association between low central CSF 5-H1AA levels with both impulsive aggression and violent suicide, the results of such studies in patients with repetitive self mutilation have been mixed—with some, but not all, ﬁ  nding 
similar reductions.
(38,39)  One study found that broadly-deﬁ  ned self 
harm was associated with allelic variation in the tryptophan hydroxylase gene (TPH A779C), but not with polymorphisms of ﬁ ve other serotonergic genes.
(40)
Studies have found increased pain thresholds in borderline person-
ality patients with repetitive self mutilation who are analgesic to 
the pain of their self injurious behaviour, suggesting dysfunction 
the endogenous opioid system.(38,39)  In support of this possibility,

the endogenous opioid system.(38,39)  In support of this possibility, 
one study found elevated plasma metenkephalin studies in a small group of analgesic self-injuring persons. Another study, however, found pretreatment with naltrexone did not reduce the anesthesia (as evaluated by the cold pressor test) of a similar group of subjects.
(39)
There are no controlled treatment studies of narrowly-deﬁ  ned 
repetitive self-mutilation. However, two psychological treatments, dialectal behaviour therapy and psychoanalytically-oriented partial 
hospitalization, have each been shown superior to ‘treatment as usual’ in decreasing chronic parasuicidal behaviour in women with borderline personality disorder.
(39) In addition, a 1998 meta-
analysis of 20 treatment trials of broadly-deﬁ  ned deliberate self 
harm indicated signiﬁ  cantly reduced repetition of self harm for

harm indicated signiﬁ  cantly reduced repetition of self harm for 
problem solving therapy and provision of an emergency contract card in addition to standard care.
(41)
Regarding medical treatments, agents with antidepressant, 
mood-stabilizing, antipsychotic, anticonvulsant, and anti-opiate properties have been reported to be effective in case reports or case series.
(12,33,39) In the above noted 1998 meta-analysis, a signiﬁ  -
cantly reduced rate of further self harm was observed for depot ﬂ upenthixol versus placebo in the one study of antipsychotic 
medication that was located and analyzed.
(41) The two studies of 
antidepressants evaluated, however, showed no beneﬁ  t.
Pathological skin picking
Pathological skin picking (also called neurotic or psychogenic 
excoriation, compulsive skin picking, dermatotillomania, and acné

excoriation, compulsive skin picking, dermatotillomania, and acné 
excorié ) is excessive scratching, picking, gouging, or squeezing of 
the skin sometimes in response to an itch or other skin sensation or to remove a lesion on the skin.
(42,43)  Most patients use ﬁ  ngernails 
to excoriate the skin, but the teeth and instruments (for example, tweezers, nail ﬁ  les, pins, or knives) are also used. Pathological skin 
picking causes substantial distress in patients, with most experienc-ing functional impairment and many reporting medical complica-tions, some severe enough to warrant surgery.
Although not recognized as a distinct DSM-IV or ICD-10 dis-

order, pathological skin picking resembles an impulse control disorder in that patients sometimes experience an increase in ten-sion prior to picking with transient relief or pleasure with picking or immediately afterwards. Many patients ﬁ  nd themselves acting 
automatically. It also has compulsive features, in that it is repetitive, ritualistic, anxiety reducing, often resisted, and egodystonic. Moreover, some patients describe obsessions about an irregularity 
on the skin or preoccupations with having smooth skin.
Pathological skin picking may occur in about 2 per cent of derma-
tology clinic patients, predominately in women, and up to 3.8 per cent of college students.
(42,43)  The disorder may begin in adoles-
cence or adulthood, and the mean duration of symptoms has ranged from 5 to 18 years, with a better prognosis for patients who have had the symptoms for less than 1 year.
(42)

(42)
Pathological skin picking often co-occurs with mood, anxiety, and somatoform disorders.
(42) It is especially common in body dys-
morphic disorder.(43) The comorbidity of pathological skin picking 
and personality disorders has not been systematically studied.
Preliminary family history data suggest ﬁ  rst-degree relatives of 
probands with pathological skin picking may have elevated rates of mood and substance use disorders.
(42)4.13.1 impulse control disorders

SECTION 4  clinical syndromes of adult psychiatry 918
Various behavioural treatments (e.g. habit reversal) may be effec-
tive in pathological skin picking.(12) One small placebo-controlled 
trial (N =21) found that ﬂ  uoxetine (mean dose of 55 mg/day) may 
be beneﬁ  cial(12). Other serotonin reuptake inhibitors, the tricyclic 
doxepin (which has been hypothesized to have antipruritic proper-ties due to its antihistaminic effects), inositol, the glutamate-modulating agent riluzole, and certain direct skin treatments (dermatologic and surgical) may also be effective.
(12,32,42,44,45)
Onychophagia
Onychophagia is repetitive and excessive nail-biting.(46) The 
cuticles and skin around the nails are also frequently bitten, picked, or clipped. Onychotillomania, the excessive picking, clipping, or tearing of the nail, may be a variant.
Although not classiﬁ  ed as a psychiatric disorder in DSM-IV or

Although not classiﬁ  ed as a psychiatric disorder in DSM-IV or 
ICD-10, onychophagia resembles an impulse control disorder in that the behaviour is often irresistible, automatic, and associated with an increase of tension before and relief or pleasure during or immediately after its enactment.
(46) It also has compulsive features 
in that it is repetitive, resisted, and associated with relief of anxiety.
Nail-biting is more common in children than adults, and may affect 5 to 10 per cent of adults over the age of 30 years.
(46) Boys and girls 
are affected equally until after the age of 10 years, when nail-biting becomes more common in boys.

Onychophagia may be associated with mood, anxiety, and substance use disorders. Of 25 adult subjects who underwent a medication trial for onychophagia, 17 (68 per cent) had a lifetime Axis I psychi-atric disorder—despite the exclusion of subjects with obsessive–compulsive disorder, a primary major affective disorder, current substance abuse, or psychosis.
(46) Four subjects (16 per cent) had 
at least one personality disorder.
Severe nail biting may be familial.(46,47)  Of 112 family members 
of 25 subjects entering a medication trial for onychophagia, seven (6 per cent) had severe nail-damaging behaviour, four (4 per cent) were severe nail-biters, and three (3 per cent) picked or chewed their hands or feet.
(46) In addition, twin studies have found higher

(46) In addition, twin studies have found higher 
concordance rates of nail biting in monozygotic compared with dizygotic twins.
(47)
Various cognitive behavioural therapies (especially habit reversal, but also self-monitoring, use of bitter tasting substances, compet-ing responses, and negative practice training) are probably effective in onychophagia.
(12) In the only controlled pharmacotherapy 
study of onychophagia, clomipramine (mean dose 120 mg/day) was superior to desipramine (mean dose 135 mg/day) in eliminat-ing nail-biting, reducing nail-biting severity and impairment, and in improving overall clinical progress.
(46)Conclusion

Growing research shows that the impulse control disorders are much more common than once thought to be. The consistency of the ‘structure’ of the irresistible impulse (a core disturbance of impulsivity and compulsivity) together with increasing research showing that it responds to certain treatments, especially cognitive-behavioural psychotherapies and me dical treatments with th ymolep-
tic or anticraving properties, regardless of its ‘content’ (the speciﬁ  c 
impulse experienced), strongly suggest that it is an important psychopathological symptom, and that impulse control disorders are legitimate mental disorders that are in fact likely to be related despite their apparent differences.
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4.13.2 Special psychiatric 
problems relating to gambling
Gambling is an activity with the following elements:
X A contract between two or more people, which is based on a

X A contract between two or more people, which is based on a 
forecast of the outcome of an uncertain event involving random processes.
X Property, referred to as the stake, is transferred between those 
taking part, so that some gain at the expense of others.
X The property transfer depends on the outcome or result of the 
uncertain event, which has been forecast.
X Participation is voluntary and not necessarily related to gaining 
the property, but used to obtain an experience.4.13.2 special psychiatric problems relating to gambling

SECTION 4  clinical syndromes of adult psychiatry 920
Gambling misuse is a behavioural disorder that can usually be 
recognized by the presence of any of the following features:
X Excessive gambling either in terms of the money spent or the 
time devoted.
X Intermittent or continuous preoccupation with gambling and 
the development of tolerance and craving for it.
X Loss of control over gambling and ‘chasing of losses’ , despite the 
realization that damage is resulting.
X Disorder affecting the person who is gambling and the family:
ó ﬁ nancial disturbances, such as debt and shortage;
ó social disturbances, such as loss of employment and friends, 
running away from home, eviction, marital problems, divorce, behaviour disorders in the children of the family, criminality and imprisonment;
ó psychological disturbances, such as depression and attempted 
suicide.
In the past, this syndrome has been referred to as compulsive

suicide.
In the past, this syndrome has been referred to as compulsive 
gambling. However, it is not a true obsessive–compulsive state but a heterogeneous group of conditions, characterized by excessive gambling resulting in disturbance for those involved. The term ‘pathological gambling’ is more appropriate, since it is not based on any assumptions regarding the underlying processes.
(1)
ICD-10(2) describes pathological gambling as a form of behaviour 
under ‘habit and impulse disorders’ . On the other hand, DSM-IV(3)
implies a homogeneous disease entity and provides criteria for its rec-ognition under ‘impulse-control disorders not elsewhere classiﬁ  ed’ . 
The ICD-10 approach is preferable since it emphasizes the fact that the condition is a behavioural disorder resulting from faulty habits.
Five varieties of pathological gambling can be recognized
(4,5):

(4,5):
X Subcultural gambling arises out of the person’s background, 
which is one of socially accepted heavy gambling.
X Impulsive gambling is characterized by loss of control for varying 
periods and the tendency to be associated with tolerance, craving, and dependence on the activity.
X Neurotic gambling occurs as a response to an emotional problem, 
particularly in a disturbed relationship in marriage or during adolescence.
X Symptomatic gambling occurs in mental illness, usually depres-
sion, which is the primary disorder.
X Psychopathic gambling is part of the generalized disturbance of 
behaviour that characterizes antisocial personality disorder.
Diagnosis
For various social reasons, pathological gambling is most easily recognized in men since they tend to patronize those types of gambling that have a high turnover of money so that excess is more likely to become apparent.

Women have tended to gamble on lotteries, bingo, and football 
pools. These may not involve such large sums of money and excess often presents with disturbances in the social sphere rather than 
through the accumulation of large debts. However, the greater general acceptance of gambling and the advent of remote gambling via the Internet, television, and mobile devices is changing the situation considerably.
While pathological gambling is seen in all age groups, an increas-
ing number of children and young people are presenting with the condition as a result of gambling on slot/gaming machines. Also, in recent years, remote gambling among children and young people has led to increasing problems. This is in spite of the fact that most jurisdictions treat gambling as an adult activity. Pathological gam-bling in adulthood frequently has its origins in heavy gambling in childhood and adolescence.
Aetiology and epidemiology
The nature of gambling

The experience of risk provides amusement, thrill, and excitement and is therefore pleasurable. These experiences make gambling attractive and the stake money is used to purchase them, with win-nings as an occasional bonus. A few, who gamble professionally, are also able to win money regularly because they have sources of information that reduce the uncertainty, as in betting on horses and dogs. Their gambling is planned and deliberate.
Gambling is usually organized commercially with the odds 
in favour of the provider. There is therefore an in-built ﬁ  nancial 
disadvantage to those who use the facilities. In slot/gaming machines where the provider is at a distance from the gambling event, this is often not apparent to those who take part.
Commercial gambling involves large sums of money, and has 
traditionally been conﬁ  ned to licensed premises. Those present 
have gone there because they have decided to take part in the gam-

bling. However, developments in technology have made it possible 
to provide gambling facilities on a remote basis via the Internet, television, and mobile devices.
A number of features inherent in the activity of gambling have 
effects that make it difﬁ  cult for a person to stop.
Psychological effects
X Underlying all gambling activity is operant conditioning with 
intermittent variable ratio reinforcement.(6) This is a most effec-
tive schedule for habit-formation and produces a stable, persis-tent response. Consequently, the long-term net gain or loss to those who gamble is almost irrelevant to the continuation of the activity. It is most dramatically seen in slot/gaming machines, which consequently are the main source of proﬁ  t for the gam-
bling industry.

X Rapid turnover gambling as in casinos restricts the ability of 
those who gamble to apply any considered judgement. Inevitably, gambling becomes more impulsive, easily leading to excessive participation.
X The assessment of probability of winning (psychological proba-
bility) in the gambling situation differs from the mathematical probability. At low probabilities, it is higher than the mathe-matical probability and at moderate and high probabilities, itis lower. This even occurs in people who are mathematicallyknowledgeable.

921
X In a gambling situation involving only random processes, where 
the outcome of successive events is completely independent, there is usually the irrational belief that a string of losses makes a win more likely. This is the negative recency effect, which is also referred to as the’Monte Carlo Fallacy’ since it forms the basis of many spurious gambling systems, especially in roulette. Paradoxically, it is associated with the belief that a string of wins is likely to continue (‘a lucky streak’). Also, a ‘near win’ generally tends to be treated as a prelude to a win. These illogical ways of thinking encourage continuous gambling and are exploited by slot/gaming machines and lottery scratch cards called ‘heart stoppers’ .
X Large prizes, even at very low probabilities, entice the gambler 
because of the possibility  of winning. The stimulant effect of roll-
overs in lotteries illustrates this.
X Skill in gambling is usually overrated and often implies an unre-

alistic ability to control the uncertain event that is the subject of the gamble. Thus, in dog and horse race betting, punters tend to place their bets just before ‘the off’ in the fantasy that this will affect the result.
X There is a tendency to lose track of time during a gambling 
session.
These psychological effects have been increased as a result of 
recent developments in commercial gambling.
X Loyalty cards providing rewards for money spent on gambling in 
a particular facility.
X Remote gambling on the Internet, television, and mobile devices 
has resulted in the following:
ó The convenience and anonymity of gambling being available 
in an isolated domestic setting, without the checks and con-
straints that can be exercised by the presence of others as in licensed premises.

ó Monetary credit in the form of e-cash systems, reducing the like-
lihood that those gambling will set a limit on the money staked.
ó Behavioural targeting and messages on some online gambling 
sites encouraging further gambling when an attempt is made to stop.
ó Difficulty in preventing children and young people from 
having access, especially since the advent of online social networks.
Physical effects
X A gambling loss in normal subjects immediately results in
particular localized activity in the medial frontal cortex of the brain. This is then associated with subsequent more risky  gam-
bling choices. This is consistent with the negative recency effect.
X Disturbances involving the reward pathways in the brain are 
signiﬁ  cantly associated with excessive gambling.
X There is a great range and strength of emotions during gambling

X There is a great range and strength of emotions during gambling 
decisions associated with cortical responses in the brain to the expectation of winning money.
X Even normal, social levels of drinking alcohol that alter self-
control over decision-making, increase the difﬁ  culty in deciding 
at what point to stop, when losing, in a gambling situation.Predisposing factors
In the presence of available gambling facilities, certain predisposi-tions may increase the likelihood of pathological gambling.
Morbid risk-taking
Since gambling is a type of risk-taking, it lends itself to be used by those who, for reasons related to their personality, have a high need for risk. They spend large sums of money on the intangible commod-ity of risk, which may easily pass unnoticed because it is ﬂ  eeting.
This morbid propensity to take risks shows itself in other ways.

This morbid propensity to take risks shows itself in other ways. 
Thus, the incidence of attempted suicide is high among those whose gambling is pathological.
(5)
Other personality factors
Freud’s formulation of gambling was that it resembles masturba-tion, is a substitute for it, and is resorted to in the context of unresolved Oedipal difﬁ  culties.
(7) Others have pointed out that 
pathological gambling may be a manifestation of self-punishment, with an unconscious desire to lose, arising from a psychological mechanism referred to as ‘psychic masochism’ .
(8)
Those whose gambling is pathological appear to have other 
predisposing personality traits. They view their behaviour as being largely determined by factors outside their personal control. They also tend towards greater impulsivity.
(5,9)
Learning processes

(5,9)
Apart from the winnings and losses, the gambling situation itself may affect learning. As far as the random processes inherent in gambling are concerned, all participants, even a total failure, stand on an equal footing. This may be the only circumstance in which some people have this experience. Gambling may therefore provide a means of dealing with morbid anxiety in the presence of feelings of inadequacy, leading to a conditioned avoidance reaction.
Mental disorder

Pathological gambling may occur in any mental disorder. However, it is most commonly associated with depression. More usually, a neurotic type of depression occurs after a bout of heavy gambling with large losses. In symptomatic pathological gambling, the depression is primary and the gambling is a response to the tension and feelings of guilt that occur in depression. This latter situation is similar to alcohol misuse and shoplifting, as part of the depressive syndrome. Pathological gambling may also be a manifestation of antisocial personality disorder.
Misuse of alcohol and pathological gambling can occur together; 
either may be the primary disorder and either may lead to the other.
Constitutional factors and physical disorder
Twin studies have demonstrated that the likelihood of pathological gambling occurring in a person is inﬂ  uenced, to an important 
degree, by inherited factors and/or experiences shared during childhood.
(10)

(10)
There also appears to be a significant association between 
pathological gambling and genetic abnormalities involving the dopamine reward pathways.
(11) Disturbances of serotonergic, 
noradrenergic, and dopaminergic neurotransmitter systems have 4.13.2 special psychiatric problems relating to gambling

SECTION 4  clinical syndromes of adult psychiatry 922
all been implicated in the aetiology of pathological gambling. This 
is particularly so in relation to the arousal, behavioural initiation, behavioural disinhibition, and reward/reinforcement mechanisms that are evident in this condition.
(12)
There have been reports of pathological gambling associated 
with dopamine agonist administration for Parkinsonism.(13)
The natural history of pathological gambling is one characterized by exacerbations and remissions, often related to life events. Important elements in this are relationships within the family, especially with the spouse/partner. An example of this is the not infrequent sequence of an exacerbation of heavy gambling in the husband, at the time of the wife’s ﬁ  rst pregnancy.
The outlook in pathological gambling is usually determined by

The outlook in pathological gambling is usually determined by 
the integrity of the underlying personality. In those in whom the condition appears as a symptom of a neurotic disorder or depression, the prognosis depends on that of the underlying disorder.
Management and treatment
Pathological gambling involves a whole way of life, which has many ramiﬁ  cations. If its management is to be successful, there need to 
be major changes in the lifestyle of the person concerned. It is best dealt with by a team approach involving at least a psychiatrist, psy-chologist, and social worker and must include the spouse/partner. Recently, counselling services have been set up but their efﬁ  cacy has 
yet to be established.
Assessment of the problem
The following aspects are important:
X An appraisal of the extent and amount of present gambling.
X A history of the development of the gambling from its early

X A history of the development of the gambling from its early 
beginnings, which is best done if the person being assessed pro-vides the information by means of a detailed written narrative.
X A discussion of this written narrative.
X An indication of the person’s motivation, since many who seek 
help for pathological gambling readily admit that they enjoy it and only want assistance for the problems that have resulted.
X At least initially, an immediate period of total abstinence from 
gambling.
Supervision of the ﬁ  nances
Excessive gambling is usually associated with a disturbed apprecia-
tion of the value of money. In view of this and the continued temptation to gamble, the family ﬁ  nances should be dealt with as 
follows:
X All monies should be controlled, at least for some time, by the 
spouse/partner or some trusted person.

follows:
X Regular income from wages/salaries should be paid into a bank 
account over which the spouse/partner or trusted person has sole control.
X A detailed statement should be drawn up of all the outstanding 
debts, as well as an inventory of the income and outgoings of the person-seeking help and his or her family.X The person whose gambling has been pathological should discuss 
the matter with all creditors and agree a repayment plan. This should be consistent with the person’s regular income andcircumstances to avoid a situation where there would be the temptation to gamble in order to maintain repayments. Since debts are often considerable, these may have to continue over many years.
X After a period of abstinence from gambling, the person
whose gambling has been pathological needs to become gradu-ally involved in working jointly with whoever controls the ﬁ nances.

Counselling
On the basis of information obtained during the course of
the initial assessment, the following aspects need furtherconsideration:
X The features inherent in gambling that affect people so that they 
ﬁ nd it difﬁ  cult to stop should be highlighted and discussed.
X Social relationships of the person whose gambling has become 
pathological and the spouse/partner should be reviewed, espe-cially if there have been serious marital problems predating the pathological gambling.
X The way spare time is spent, what friends are cultivated, and what 
interests are pursued should be reviewed. Since incitement to gamble will have occurred in the past within speciﬁ  c settings, 
arrangements need to be made to avoid these or, at least, to be prepared for them.

X A joint contract to be reviewed regularly spelling out in detail 
those types of behaviour to be avoided as well as those to be encouraged may be found helpful.
Gamblers Anonymous
This form of self-help for pathological gambling is organized in regular local groups. As well as meetings for those who have agambling disorder, there are also separate ones for their spouses/partners. Quite apart from the valuable work done in the group setting, Gamblers Anonymous provides a useful means ofestablishing alternative social contacts from those that were associ-ated with gambling. Indeed, for some people, Gamblers Anonymous may be the vehicle through which all the necessary help can beprovided. Even if this is not the case, Gamblers Anonymousstill provides a valuable form of support for the individual and the family.

A variety of psychological treatments have been advocated but, in general, their long-term efﬁ  cacy has not been established. 
A good outcome has been reported after a cognitive behavioural approach.
(14) Also, controlled gambling, rather than permanent 
abstinence, has led to a reported successful outcome after behav-ioural treatment.
(15)
Psychiatric treatments
Specialist treatment from a psychiatrist and/or a psychotherapist for a neurotic disorder or severe depression may be required, if these clearly underlie the pathological gambling.

923
In view of the nature of gambling and the importance of the social 
causation of pathological gambling, it is vital that it should be seen as an activity that requires moderation. Unfortunately, the recent increasing reliance of governments and states on gambling for revenue purposes is resulting in a vast growth in the availability of gambling facilities and the incitements to participate.
This has been associated with public policies that actively pro-
mote gambling and also claim to encourage moderation. The inconsistency in trying to do both inevitably has a harmful effect on any educational attempt to provide a sensible attitude to gambling. It also undermines any help for those whose gambling has become excessive.
Journal of Gambling Studies . Springer. http://www.springer.com/west/home/
social+sciences/sociolo gy?SGWID=4-40440-70-35680327-0 Online

version available http://www.springerlink.com/content/1050-5350 International Gambling Studies . Routledge. http://www.informaworld.
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on gambling behaviour: an analysis of 3359 twin pairs. Addiction ,
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11. Cummings, D.E. (1998). The molecular genetics of pathological

11. Cummings, D.E. (1998). The molecular genetics of pathological 
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86, 299–306.4.13.2 special psychiatric problems relating to gambling

4.14
Sleep–wake disorders
4.14.1 Basic aspects of 
sleep–wake disorders
A sound working knowledge of the diagnosis, signiﬁ  cance, and 
treatment of sleep disorders is essential in all branches of clinical psychiatry. Unfortunately, however, psychiatrists and psychologists share with other specialties and disciplines an apparently universal neglect of sleep and its disorders in their training. Surveys in the United States and Europe point to the consistently meagre coverage of these topics in their courses at both undergraduate and post-graduate levels.
The following account is an introductory overview of normal 
sleep, the effects of sleep disturbance, sleep disorders and the risk of failure to recognize them in psychiatric practice, assessment of sleep disturbance, and the various forms of treatment that are available. The aim is to provide a background for the other chapters in this section.

The close links between the ﬁ  eld of sleep disorders and psychia-
try which make it essential that psychiatrists are familiar with the ﬁ eld are as follows:
X Sleep disturbance is an almost invariable feature and complica-
tion of psychiatric disorders from childhood to old age, with the risk of further reducing the individual’s capacity to cope with 
their difﬁ  culties (see Table 4.14.1.3 for further details).
X Sleep disturbance can presage psychiatric disorder.
X Some psychotropic medications produce significant sleep 
disturbance.
X Of importance to liason psychiatry is the fact that many general 
medical or paediatric disorders disturb sleep sufﬁ  ciently to 
contribute to psychological or psychiatric problems.
X Because of lack of familiarity with sleep disorders and their

X Because of lack of familiarity with sleep disorders and their 
various manifestations, such disorders may well be misinterpreted as primary psychiatric disorders (or, indeed, other clinical condi-tions) with the result that effective treatments for the sleep disor-der are unwittingly withheld (see later).
Some of these points will be ampliﬁ  ed in later sections of this chapter.
Basic features of normal sleep
The scientiﬁ  c study of sleep and its disorders is largely conﬁ  ned to 
the last several decades. Essentially interdisciplinary advances have displaced earlier speculative accounts including those in psychiatry concerning the signiﬁ  cance of dreams, for example. They are well 
described in recent textbooks of sleep disorders medicine (see rec-ommended sources). Only general points are mentioned here, with special reference to psychiatry where possible.

The nature of sleep
Sleep has characteristic physiological features which distinguish it from other states of relative inactivity. Two distinct sleep states have been deﬁ  ned, that is non-rapid eye movement ( NREM ) sleep and 
rapid eye movement ( REM ) sleep. The onset of sleep is not simply 
the shutdown of wakefulness but also the switching between wakefulness, NREM and REM sleep involve complicated active neurochemical mechanisms in different parts of the brain.
The functions of sleep
Debate continues about the various theories concerning sleep, each of which has emphasized physical and psychological restoration and recovery, energy conserv ation, memory consolidation,  discharge

of emotions, brain growth and various other biological functions including somatic growth and repair, and maintenance of immune Contents
4.14.1 Basic aspects of sleep–wake disorders
 4.14.2 Insomnias
 4.14.3 Excessive sleepiness
 4.14.4 Parasomnias

925
systems. No one theory accounts for all the complexities of sleep 
and it seems likely that sleep serves multiple purposes.
From the practical point of view, the most obvious observation is 
that both physical and psychological impairment follows persistent 
sleep disturbance. Animals totally deprived of sleep for a long periods 
die with loss of temperature regulation and multiple system failure. 
As described later, the adverse effects of chronic sleep loss (consid-
ered to be common in modern society) on mood, behaviour, 
and cognitive function can be substantial, with various conse-
quences for personal, social, occupational, educational, and family 
Sleep stages
Conventionally, standard criteria are used to identify different 
sleep stages according to their characteristic physiological features 
especially in the electroencephalogram ( EEG ), electrooculogram 
(EOG ), and electromyogram ( EMG ).
NREM sleep  is divided into four stages of increasing depth.

NREM sleep  is divided into four stages of increasing depth. 
Stage I  occurs at sleep onset or following arousal from another 
stage of sleep. This stage represents 4–16 per cent of the main sleep 
period. Stage II  contains more slow EEG activity but is still rela-
tively light sleep. It accounts for 45–55 per cent of overnight sleep. 
Stage III  (4–6 per cent of total sleep time) contains yet more slow 
EEG activity. Stage IV  is characterized by the slowest activity and 
constitutes 12–15 per cent of sleep. The combination of stages III 
and IV is called slow wave sleep ( SWS ) or delta sleep and is consid-
ered to be the deepest form of sleep from which awakening is 
particularly difﬁ  cult. The arousal disorders such as sleepwalking 
arise from SWS.
REM sleep  is physiologically very different. Brain metabolism is 
highest in this stage of sleep. Spontaneous rapid eye movements

highest in this stage of sleep. Spontaneous rapid eye movements 
are seen and the skeletal musculature is effectively paralysed. Heart 
rate, blood pressure, and respiration are all variable, body tempera-
ture regulation ceases temporarily, and penile and clitoral tumes-
cence occurs. REM sleep usually takes up 20–25 per cent of total 
sleep time. Most dreams, including nightmares, occur in REM sleep.
Sleep architecture
NREM and REM sleep alternate cyclically throughout the night 
starting with NREM sleep lasting about 80 min followed by about 
10 min of REM sleep. This 90 min sleep cycle is repeated three to six 
times each night. Each REM period typically ends with a brief 
arousal or transition into light NREM sleep.
In successive cycles the amount of NREM sleep decreases and the 
amount of REM sleep increases. SWS is usually conﬁ  ned to the ﬁ  rst

amount of REM sleep increases. SWS is usually conﬁ  ned to the ﬁ  rst 
two sleep cycles. The diagrammatic representation of overnight 
sleep is known as a hypnogram , a simpliﬁ  ed form of which is 
shown in Fig. 4.14.1.1.
In addition to this conventional sleep staging, there has been 
increasing interest in the microstructural fragmentation of sleep by 
frequent, brief arousals (seen mainly in the EEG) lasting a matter 
of seconds without obvious clinical accompaniments. This subtle 
type of sleep disruption, overlooked by conventional sleep staging, 
is increasingly associated with impairment of daytime performance, 
mood, and behaviour.
Circadian sleep–wake rhythms
The timing of sleep (but not its amount) is regulated by a circadian 
‘clock’ in the suprachiasmatic nucleus ( SCN ) of the hypothalamus. The intrinsic circadian sleep–wake rhythm is close to 24 h in human

‘clock’ in the suprachiasmatic nucleus ( SCN ) of the hypothalamus. The intrinsic circadian sleep–wake rhythm is close to 24 h in human 
adults. Other species are different, an extreme example being 
dolphins and some other creatures which shut down one cerebral 
hemisphere at a time (‘unihemispheric sleep’), allowing them to be 
constantly alert. From an early age the individual sleep–wake 
rhythm has to synchronize with the 24-h day–night rhythm. The 
main zeitgeber  by which this is achieved (‘entrainment’) is sunlight 
but social cues, such as mealtimes and social activities, are also 
important.
The SCN also controls other biological rhythms including body 
temperature and cortisol production with which the sleep–wake 
rhythm is normally synchronized. In contrast, growth hormone is 
locked to the sleep–wake cycle and is released with the onset of 
SWS, whatever its timing.
Melatonin  is related to the light–dark cycle rather than the

Melatonin  is related to the light–dark cycle rather than the 
sleep–wake cycle. It is secreted by the pineal gland during darkness 
and suppressed by exposure to bright light (‘the hormone of 
darkness’). It inﬂ  uences circadian rhythms via the SCN pacemaker 
which in turn, regulates melatonin secretion by relaying light 
information to the pineal gland. The widespread popularity of 
melatonin as a sleep-promoting agent is not justiﬁ  ed by what little 
is known about its action and clinical effectiveness.
Changes with age
Changes in basic aspects of sleep are prominent from birth to old 
age, although individual differences are seen at all ages. Changes of 
clinical signiﬁ  cance include the following:
XT otal sleep time  decreases with age. Average daily values are as 
follows: newborns 6–18 h; young children 10 h; adolescents 9 h

follows: newborns 6–18 h; young children 10 h; adolescents 9 h 
(although often they obtain signiﬁ  cantly less than this); adults 
7.5–8 h, including possibly the same in elderly people. The total 
amount of sleep includes daytime napping in children up to the 
age of about 3 years.
XSWS  is particularly prominent in prepubertal children who sleep 
very soundly. Its decline begins in early adolescence and continues 
throughout childhood.
X The proportion of REM sleep  declines from 50 per cent or more 
of total sleep time in the newborn (more than this in premature 
babies) to 20–25 per cent by 2 years. This ﬁ  gure remains fairly 
constant throughout the rest of life. The high level of REM sleep 
in very early life suggests a role in cerebral maturation but the 
reason for its persistence throughout life is unclear. Memory

reason for its persistence throughout life is unclear. Memory 
processing appears to depend on sleep. However, people deprived Fig. 4.14.1.1 Diagram of an overnight hypnogram in a young adult.
4.14.1 basic aspects of sleep–wake disorders

SECTION 4  clinical syndromes of adult psychiatry 926
of REM sleep, experimentally or pathologically, can be relatively 
unaffected either emotionally or cognitively. Deep sleep decreases in the elderly.
XNREM–REM sleep cycles  occur at intervals of 50–60 min in 
infants who often enter REM at the start of their sleep period. This interval between sleep cycles remains until adolescence when the periodicity changes to 90–100 min, which persists into adult life. The amounts of NREM and REM in each sleep cycle is about equal in early infancy. Afterwards, NREM sleep (especially SWS) predominates in the earlier cycles and REM sleep in the later cycles.
XContinuity of sleep  is greatest in pre-pubertal children (as 
mentioned previously) and least at the extremes of age. Infants are easily awakened and so are the elderly who also wake sponta-neously more often. Fragmentation of sleep by brief arousals, or very brief awakenings, is particularly common in old age.

XCircadian sleep–wake rhythms  change considerably in early 
development. Full-term neomates show 3–4-h sleep–wake cycles. Sleep periods have largely shifted to the night and wakefulness to daytime by 12 months, except for napping which gradually dimin-ishes and has usually stopped by about 3 years of age. However, a physiological tendency towards an afternoon nap remains throughout the rest of the life. Although repeated brief waking at night is more common in infancy and early childhood than later, it remains a normal occurrence throughout life, increasing in frequency again in old age. The clinical problem arises when there is difﬁ  culty returning to sleep after such awakenings.
Psychological effects of sleep disturbance
There is extensive clinical and experimental evidence that sustained 
sleep disturbance can have serious adverse psychological effects.(1,2)
The term sleep disturbance covers the following:
X Loss of sleep (i.e. shortened duration).

X Impaired quality of sleep (repeated disruption of sleep 
architecture).
X Inappropriate timing of the sleep period in relation to day–night 
rhythms (as in the various circadian sleep rhythm disorders such as jet lag, shift work, or the more frequently encountered forms seen in clinical practice, as discussed later).
Experimental studies of total sleep loss  demonstrate a progressive 
deterioration in cognitive function, mood, and behaviour related to length of sleep loss. However, inter- and also intra-individual differences in susceptibility are seen, reﬂ  ecting such factors as

motivation, personality, and usual sleep requirements. Task charac-teristics (e.g. brief or prolonged and monotonous tasks), timing of the task in relation to the circadian sleep–wake rhythm, and physical environmental factors such as noise and other distracting stimuli, are also important.
Variations for similar reasons are important in partial sleep 
deprivation  experiments which (like those concerning fragmenta-
tion of sleep) are much closer to real-life sleep disturbance caused by social activities, job demands, and other aspects of modern life-style. These studies raise the issues of how much sleep is needed for optimal daytime functioning and whether these requirements are not being met. It has been argued that there is ‘national sleep debt’ in the United States and other western countries, and that bysleeping longer than they do habitually, many people would increase 
their performance and improve their well-being during the day.

The usual subjective effects of sleep disturbance are irritability, 
fatigue, poor concentration, and depression. More dramatic effects are described with prolonged and severe sleep disturbance, such as disorientation, illusions, hallucinations, persecutory ideas, and inappropriate behaviour with impaired awareness (‘automatic behaviour’) caused by frequent microsleeps. Psychometric studies have shown that sleep disturbance can produce a range of cognitive impairments, again depending on its duration and individual susceptibility. Sustained attention (vigilance) is particularly vulnerable and possibility abstract thinking and divergent intelli-gence or creativity.
The experimental ﬁ  ndings are in keeping with the results from

studies of various occupational groups including junior hospital doctors and drivers of various types of vehicle, in which reduced performance or accidents are associated with sleep disturbance. The common and increasing practice of night-shift work (as part of the ‘24 h society’) is contrary to the fundamental biorhythm of sleeping at night and being awake during the day, and is often accompanied by a reduction in total sleep time and poor quality sleep. It is not surprising that working shifts commonly results in loss of well-being, physical complaints, and impaired productivity and safety, as well as physical disorders. Similarly, the distribution over the 24 h period of road accidents (especially those not involv-ing other vehicles) and other mishaps at work, correspond to that of the levels of sleep tendency assessed objectively. Even industrial and engineering disasters have been attributed to sleep loss and impaired performance on the part of key personnel.

Additional evidence that sleep disturbance affects daytime func-
tion comes from neuropsychological studies of certain sleep disor-ders. Impaired performance on prolonged and complex tasks of 
subjects with narcolepsy has been shown to be secondary to the effects of their daytime sleepiness rather than an intrinsic neuro-
logical deﬁ  cit. In the many adult patients with obstructive sleep 
apnoea, attention memory impairment (like depression and irrita-bility commonly reported by these patients) are also largely attributable to daytime sleepiness. There is some evidence that deﬁ cits in more complicated ‘executive functions’ (formulating 
goals, planning, and carrying out plans effectively) are not neces-sarily reversed when their sleepiness is relieved by treatment. This might be the result of irreversible anoxic brain changes in the later stages of the condition. Clearly, early detection and treatment of this condition is essential to prevent this happening.

When return to normal sleep is possible, recovery from short 
periods of sleep disturbance occurs after much less sleep than that originally lost, for example, after one night’s sleep following sleep loss over several days and nights. Reversal of the effects of long sleep disturbance in real-life is likely to be complicated, for example by emotional consequences of the disturbance.
Many of the above observations about the psychological effects 
of sleep disturbance (and their reversibility) have been madeon young adult subjects or patients. The area is largely unexplored in other age groups but there is no reason why the generalprinciple should not apply to children and the elderly including demented patients in whom sleep disturbance is particularlyprominent.
Another group on whom further research is particularly required 
are people with learning disabilities (intellectual disability).

927
The available literature provides good reason to believe that

the sleep disorders, especially in the more severely disabledgroups, not only affects the majority but also are unusually severe and long-lasting because of lack of appropriate advice andtreatment. The sleep  disturbance is a problem in its own right and is often associated with various cognitive and behavioural abnormalities which might, at least partly, be the consequence of the sleep disturbance. Sleep disturbance in the duration or the quality of sleep may be one of the few ways of improving to some extent the psychological well-being of people with learn-ing disabilities or dementia (and that of their carers) whose basic condition itself cannot be improved. In the case of the learning disabled, contrary to the common supposition by both profes-sionals and relatives, success can usually be achieved (even in severe and long-standing problems), given an accurate diagnosis of the type of sleep disorder which may be predominantly behav-ioural or physical in type depending on the cause

be achieved (even in severe and long-standing problems), given an accurate diagnosis of the type of sleep disorder which may be predominantly behav-ioural or physical in type depending on the cause of the learning disability.

Sleep disturbance in the aetiology of 
psychiatric illness
Various ‘psychotic’ and other abnormal psychological phenomena 
were mentioned earlier resulting from prolonged and severe sleep disturbance, but these are reversed when normal sleep is restored. It remains an open question how often sleep disturbance is a primary cause of psychiatric illness. Evidence is patchy, tentative, and still in need of clariﬁ  cation.
X Over a wide age range, patients with a prior history of insomnia 
have been found consistently to be at signiﬁ  cantly increased 
risk for severe depression. This could be interpreted in different ways including that sleep disturbance and the depression have a common underlying pathology, or that the sleep problems are an early sign of depression.
X A less fundamental role (but again implying preventative possi-
bilities) is the suggestion that sleep deprivation late in pregnancy and in labour and childbirth at night might trigger post-natal depression.

X Abnormal circadian sleep–wake rhythms have been implicated 
in various depressive disorders including seasonal affective disorder (SAD). Light therapy has been used to correct the abnormality and relieve the depression and other symptoms.
X Disordered REM sleep mechanisms have (questionably) been con-
sidered as fundamental in the development of post-traumatic stress disorder symptoms.
X Some forms of attention-deficit hyperactivity disorder in 
children are attributed to persistent sleep disturbance.
X In a proportion of patients with schizophrenia, narcolepsy has 
been reported as the cause of their psychotic symptoms.
Disorders of sleep
Sleep complaints
The starting point for the clinician is the patient’s sleep complaint. They are of three basic types:

X Not enough sleep, or unrefreshing sleep ( insomnia ).X Sleeping too much ( excessive daytime sleepiness  or 
hypersomnia ).
X Disturbed episodes during or otherwise related to sleep 
(parasomnias ).
The detailed accounts later in this section are organized in relation 
to these main types of sleep complaint: insomnias (Chapter 4.14.2); excessive daytime sleepiness (Chapter 4.14.3); and parasomnias (Chapter 4.14.4). Sleep problems in childhood and adolescence are discussed in Chapter 9.2.9.
Whatever the clinical setting in which sleep complaints are inves-
tigated, the essential aim is to identify the speciﬁ  c sleep disorder 
from the many other conditions that can give rise to such complaints.

from the many other conditions that can give rise to such complaints. 
Some sleep disorders may cause more than one type of complaint, and a patient may have more than one sleep disorder. The question arises how best to classify the many sleep disorders that have been described.
International classiﬁ  cation of sleep disorders—second 
edition 2005 (ICSD-2)
This system, derived from wide international consultation, is the 
latest attempt to organize rationally the many ways in which sleep can be disturbed. ICSD-2 replaced the ICSD-Revised scheme outlined in the ﬁ  rst edition of this textbook. More than 90 different 
sleep disorders are grouped as shown  in Table 4.14.1.1.  The grouping 
reﬂ ects the fact that knowledge about individual sleep disorders is

reﬂ ects the fact that knowledge about individual sleep disorders is 
very varied. The basic pathophysiology of some is quite well docu-mented; in others little is known beyond their manifestations, and even they are subject to change as clinical observations improve. As a result, the ICSD-2 groupings are a mixture of those based on a common complaint (e.g. insomnia or hypersomnia), others on presumed aetiology (circadian rhythm sleep–wake disorders), and yet others are grouped according to the organ system from which the problems arise (such as sleep-related breathing disorders). Two additional groups in the system reﬂ  ect current uncertainty about 
their status as disorders, or about their true nature.
Each sleep disorder is described in a standardized fashion using a

Each sleep disorder is described in a standardized fashion using a 
series of sub-headings which include clinical features, demograph-ics, pathology, and differential diagnosis. Treatments are notcovered. Some publications are recommended concerning each sleep disorder. An attempt has been made throughout ICSD-2 to highlight aspects of sleep disorders of particular relevance tochildren.
In all, ICSD-2 provides a concise, easily accessible and up-to-date 
source of information for consultation by the clinician. Without being over-technical, it is more comprehensive and informative than current ICSD-10 and DSM-IV systems.
Sleep disorders mistaken for primarily 
psychological or psychiatric conditions
Sleep disorders manifest themselves in many ways. Failure to real-

ize this can result in the misdiagnosis of primary sleep disorders as other types of clinical conditions of psychiatric, neurological, or otherwise medical conditions especially if there is limited familiar-ity with the sleep disorders ﬁ  eld (which, unfortunately, is generally 
the case). Clearly such mistakes compromise patient care. The fol-lowing are some of the main examples of this problem. Further details, with examples, are available elsewhere.
(3)4.14.1 basic aspects of sleep–wake disorders

SECTION 4  clinical syndromes of adult psychiatry 928
X Persistently not obtaining enough sleep, or having poor quality 
sleep because of interruptions by frequent subclinical arousals 
(as in obstructive sleep apnoea), is likely to cause tiredness, 
fatigue, irritability, poor concentration, impaired performance 
(possibly causing injuries or accidents at work or while driving), 
or depression. Out of the various possible explanations for such changes of behaviour, sleep disturbance may well be overlooked with failure to appreciate that, with improvement in sleep (which is usually possible with the right advice), such problems can be resolved. Occupational groups at special risk of sleep disturbance and its harmful effects include some clinicians.X Excessive sleepiness, whatever its cause out of the many possibili-

ties including physical conditions, is often misjudged as laziness, disinterest, daydreaming, lack of motivation, depression, intel-lectual inadequacy, or a number of other unwelcome states of mind. Sometimes, in very sleepy states, periods of ‘automatic behaviour’ occur, i.e. prolonged, complex, and possibly inappro-priate behaviour with impaired awareness of events and, there-fore, amnesia for them. Such episodes, the result of repeated ‘microsleeps’ , can easily be misconstrued as reprehensible or dis-associative features, misbehaviour, or prolonged seizure states. The paradoxical effect in young children of sleepiness causing 
over-activity has sometimes led to a diagnosis of attention-deﬁ  cit 
hyperactivity disorder (ADHD) inappropriately treated with stimulant drugs instead of treatment for the sleep disorder.
A number of speciﬁ  c sleep disorders are at particular risk of 
being misinterpreted.
X In so-called delayed sleep phase syndrome, in which there is

X In so-called delayed sleep phase syndrome, in which there is 
difﬁ culty getting to sleep until very late, and problems getting up 
in the morning because of a shift in this timing of the sleepphase, is considered to be particularly common in adolescents who may be mistakenly thought to be awkward, lazy, irresponsi-ble, or indulging in school refusal of the more usual type. Infact, this sleep disorder at that age is the result of a combination of normal pubertal biological body clock changes and alterations in lifestyle involving staying up late for social reasons or for study.
X It is not generally appreciated that even very complicated behav-

iour is possible whilst a person is still asleep as in sleepwalking episodes. Those with agitated sleepwalking or sleep terrors may appear to be very fearful and distressed and rush about and cry out as if escaping from danger. Other sleepwalkers develop an eating disorder with excessive weight gain due to the amount of food they consume while they are still asleep at night. Y et others behave in an aggressive or destructive way causing injury to themselves or other people and, at times sexual or other serious offences have been committed during a sleepwalking episode. If it is not known that such complicated actions are compatible with still being asleep, it is likely to be assumed that the person was awake at the time and aware of what he or she was doing, and, therefore, responsible for what had happened.
X Obstructive sleep apnoea is another case in point where this

X Obstructive sleep apnoea is another case in point where this 
essentially physical disorder may be mistaken for beingsomething very different from its true nature. The impairment of sleep quality, which characterizes this condition, can cause excessive daytime sleepiness, changes of personality, as wellas adverse affects on social life and performance at work, as well as intellectual deterioration to the extent that dementia issuspected.
X Narcolepsy/cataplexy is also at serious risk of being misdiag-
nosed, sometimes for many years. Neurosis or depression is commonly mistaken for the narcolepsy symptoms.
X In REM sleep behaviour disorder there is a pathological reten-
tion of muscle tone during REM sleep so that a person can act out their dreams and behave violently if they have violent dreams. The dramatic behaviour that may result, including attacks on the sleeping partner, is easily misconstrued as intentional aggression.Table 4.14.1.1  ICSD-2 groups of sleep disorders

I Insomnias
The many psychological and physical causes of difﬁ  culty getting off to sleep, 
not staying asleep, early morning wakening, and feeling un-refreshed by sleep 
are included here including stress, poor sleep habits, and various mental and medical conditions.
II Sleep-related breathing disorders
This group includes the common condition of obstructive sleep apnoea 
in adults and in children which often causes daytime sleepiness and other 
serious effects including changes in mood and behaviour. Central apnoea and various types of hypoventilation/hypoxaemic syndromes are also part of this 
group.
III Hypersomnias of central origin not due to a circadian rhythm sleep disorder, 
sleep-related breathing disorder, or other cause of disturbed nocturnal sleep
Included here are narcolepsy and the causes of intermittent or recurrent 
hypersomnia such as the Kleine–Levin syndrome.
IV Circadian rhythm sleep disorders

These disorders are characterized by a mistiming (and often disruption) of the 
sleep period, resulting in insomnia and/or hypersomnia. A prominent example 
is the delayed sleep phase syndrome common in adolescence. The advanced sleep phase syndrome can be seen in the elderly in which the sleep period 
begins in the evening with waking early when sleep requirements have been 
met. Irregular sleep–wake rhythms may be the result of an ill-organized way of life and substance abuse. Jet lag and nightshift work disorder are further 
examples of sleep problems caused by disturbance of the biological clock 
controlling the sleep–wake cycle.
V Parasomnias
These are abnormal behaviours or sensations during or otherwise closely 
related to sleep. Many can be categorized according to the stage of sleep with

related to sleep. Many can be categorized according to the stage of sleep with 
which they are usually associated for example NREM sleep (sleepwalking) and 
REM sleep (nightmares, REM sleep behaviour disorder). Other parasomnias of particular psychiatric interest include sleep-related dissociative disorders and 
sleep-related eating disorders.
VI Sleep-related movement disorders
These include the restless leg syndrome and periodic limb movement disorder.
VII Isolated symptoms, apparently normal variants and unresolved issuesVIII Other sleep disorders
The classiﬁ  catory scheme also includes an appendix on sleep disorders 
associated with conditions classiﬁ  able elsewhere such as sleep-related epilepsy, 
headaches, gastro-oesophageal reﬂ  ux. A further appendix is concerned with 
other psychiatric and behavioural disorders frequently encountered in the

other psychiatric and behavioural disorders frequently encountered in the 
differential diagnosis of sleep disorders. This appendix covers mood disorders, anxiety disorders, somatoform disorders, schizophrenia and other psychiatric 
disorders, personality disorders, and disorders of a psychiatric or behavioural 
type ﬁ  rst diagnosed in infancy, childhood, or adolescence.

929
X The complicated behaviour (far removed from that seen in 
other seizure states) that characterizes nocturnal frontal lobe epilepsy is often mistakenly thought to be evidence of a psychiatric disorder.
X In addition, sleep paralysis may be misconstrued as a psychotic 
disorder when (not uncommonly) accompanied by hallucinatory experiences.
In addition to sleep disorders being mistaken for psychiatric 
disorder, the opposite problem arises occasionally, that is some patients simulate excessive daytime sleepiness in order to avoid a psychologically troubling situation. Similarly, appar ent parasomnias
during sleep have sometimes been shown by polysomnography to occur when the patient is actually awake.
Detection and assessment of sleep disorders

As suggested earlier, evidence of a sleep disturbance should be actively sought in members of the general population and thevarious groups, including psychiatric patients, who are atspecial risk of sleep disorders. Otherwise, many instances of even severe sleep disturbance will continue to go unrecognized and untreated.
Sleep history
Routinely, all patients should be asked the following screening questions:
X Do you sleep long enough or well enough?
X Are you very sleepy during the day?
X Do you do unusual things or have strange experiences at night?
Ideally, their partner or other relatives should also be asked the

Ideally, their partner or other relatives should also be asked the 
same questions about the patient because the existence or severity of some forms of sleep disturbance are not known to the patient. In the case of children, parents are the main source of information but teachers’ observations about daytime sleepiness or disturbance are also important.
If the answer to any of these enquiries is positive, a detailed sleep 
history is required. As traditional clinical history-taking schedules pay little attention to sleep, additional sleep-related enquiries will need to be made, covering the following points about the sleep problem.
X Precise nature of the sleep complaint, its onset, development, 
and current patterns.
X Medical or psychological factors at the onset of the sleep 
problem or which might have maintained it.
X Patterns of occurrence of the symptoms that is factors making

X Patterns of occurrence of the symptoms that is factors making 
them better or worse, weekdays compared to weekends, or work compared with holiday periods.
X Effect on mood, behaviour, work, social life, other family 
members.
X Past and present treatments for sleep problems and their effects.
X Past and present medication or other treatments for other illness 
or disorder.
In addition, detailed information is needed concerning the 
following:X The patient’s typical 24-h sleep–wake schedule. This can usually 
start with the evening meal, followed by preparation for and timing of bedtime, time and process of getting to sleep, events during the night, time and ease of waking up and getting up, level of alertness, and mental state and behaviour duringthe day.
X An attempt should be made to establish the duration, continuity,

X An attempt should be made to establish the duration, continuity, 
and timing of the patient’s overnight sleep as these are the most important aspects of sleep for daytime functioning. It is also important to identify events of particular diagnostic signiﬁ  cance, 
for example loud snoring.
X Sleep hygiene.
Compilation of a sleep history can be aided by the use of a pre-
liminary sleep questionnaire (e.g. ref.(4)).
Sleep diary
Systematic recording in a booklet each day over 2 weeks or more, using a standardized format, avoids the bias or distortion of retrospective generalizations.
Other histories
Medical and psychiatric histories  should include past and current 
treatment details (in view of the wide range of illnesses or disorders and their treatment with which sleep disturbance is associated). Social history  should include occupational, marital, and recre-

ational factors (drinking, smoking, drug use), which may affect sleep. Family history  may be positive, for example in sleepwalking 
and associated arousal disorders.
Review of systems
Breathing difﬁ  culties and nocturia, for example, are associated 
with sleep disturbance. Severe obstructive sleep apnoea can cause cardio-respiratory and other cardiovascular complications.
Physical and mental state examination
Particular attention should be paid to the following:
X Evidence of any systemic illness including cardio-respiratory dis-
ease or neurological disorder (such as Parkinson’s disease or stroke) which may disturb sleep.
X Obesity, oral and pharyngeal abnormalities, retrognathia, or 
mid-face deformity (predisposing to upper airway obstruction).
X Depression or other psychiatric disorder.
X Intellectual impairment, especially features of intellectual
disability or dementia (including specific retardationsyndromes) in view of their strong association with sleepdisturbance.

Audio–video recording and actigraphy
Audio–video recordings  can be very instructive in the parasom-
nias, sometimes revealing a very different picture than that pro-vided in the clinic. Home video systems can be used where admis-sion to hospital is not feasible. Similarly, monitoring of body movements via means of wrist-watch-like devices ( actigraphy ) can 
be used at home, if necessary, to quantify basic circadian sleep–wake patterns.4.14.1 basic aspects of sleep–wake disorders

SECTION 4  clinical syndromes of adult psychiatry 930
Polysomnography (PSG)
Physiological sleep studies are necessary for diagnosis in only the 
minority of sleep disorders. Traditionally this has entailed admis-sion to a sleep laboratory. However, especially where such facilities are difﬁ  cult to obtain, where the laboratory situation is unacceptable 
to patients (including some children or patients who are psychiatrically disturbed), home PSG , using portable systems, is use-
ful, although the procedure has yet to be fully standardized and for some disorders is best seen as only a screening procedure. Recording 
in the home environment has the further advantage that, if the 
patient is allowed to adapt to the recording procedure before bed-time, the results from a single night’s recording can be representative of the patient’s habitual sleep. In contrast ‘ﬁ  rst night effects’ are

prominent in laboratory recordings and more than one night of polysomnography is required to allow adaptation to take place.
Basic polysomnography entails the recording of EEG, EOG, and 
EMG. This allows sleep to be staged and a hypnogram to be com-piled as illustrated in Fig. 4.14.1.1. Usually the recording is made overnight but it may be continued during the day if required. Basic measures obtained from this information are as follows: total sleep time, time awake and number of awakenings, amount of REM and NREM sleep and their distribution overnight.
PSG can be extended to additional physiological measures, 
especially the following:
X Respiratory variables and audio–video recordings for sleep-relat-
ed breathing problems.
X Additional EEG channels (combined with video) if nocturnal 
epilepsy is suspected.
X Anterior tibialis EMG for the detection of period limb move-
ments in sleep.
Main indications for PSG are:
X The investigation of excessive daytime sleepiness, including the

X The investigation of excessive daytime sleepiness, including the 
diagnosis of sleep apnoea, narcolepsy, or PLMS.
X The diagnosis of parasomnias where their nature is unclear from 
the clinical details, where PSG ﬁ  ndings contribute essentially to 
the diagnosis (e.g. REM sleep behaviour disorder), where the possibility of epilepsy exists, or whether there may be more than one parasomnia present.
X As an objective check on the accuracy of the sleep complaint, or 
response to treatment.
Further laboratory investigations may be appropriate depending on the nature of the sleep problem and the purpose of the assessment.
XA multiple sleep latency test  (MSL T ), involving the recording of 
basic PSG variables, quantiﬁ  es the degree of daytime sleepiness

basic PSG variables, quantiﬁ  es the degree of daytime sleepiness 
by measuring the time a patient takes to fall asleep during ﬁ ve opportunities to do so during the day. In adults, a mean sleep 
latency of 5 min or less indicates pathological sleepiness (usually of organic origin); 5 to 10 min is a grey area which usually includes excessive sleepiness associated with primary psychiatric disorder; while longer than 10 min is normal. These values do not apply in children whose sleep tendency varies with age.
XHLA typing , and possibly CSF hypocretin (orexin) levels  for the 
investigation of narcolepsy, and nocturnal penile tumescence monitoring  in the differential diagnosis of organic versus psy-
chogenic impotence, are examples of other speciﬁ  c tests that may 
be appropriate depending on the clinical problem.
Treatment approaches for sleep disorders

In clinical practice, the pharmacological approach to treatment of sleep problems (especially insomnia) is generally overemphasized, especially in the use of hypnotic-sedative drugs. Table 4.14.1.2 provides some indication of the wide range of available types of treatment, as well as general principles of management, for adults and children. They are roughly arranged in order of the frequency of their use in the comprehensive management of sleep disorders in general. An appropriate choice from this range requires an accurate diagnosis of the underlying sleep disorder. Further details are provided in later contributions to this section on sleep disorders. Claims for the effectiveness of these various measures are based on widespread clinical experience and reports. Few randomized controlled trials have not been published, as yet.

Certain aspects of treatment with special relevance to psychiatric 
practice are included in Table 4.14.1.3.
Clinical sleep disorders in psychiatric 
As mentioned earlier, sleep disturbance is a feature of many 
psychiatric disorders at all ages. Sometimes a sleep disturbance is profound and constitutes one of the deﬁ  ning characteristics of 
the psychiatric condition. This aspect of the psychiatric state requires careful deﬁ  nition and quite possibly treatment in its own 
right, alongside primarily psychiatric help, in order to facilitate recovery.
Table 4.14.1.3 outlines the main types of sleep problem or disor-
der associated with various psychiatric conditions. Emphasis has been placed on clinical sleep problems rather than PSG abnormali-ties which are seen in some of the conditions which (although interesting and of potential pathophysiological signiﬁ  cance) are 
Table 4.14.1.2  Examples of treatment approaches for sleep 
disorders in adults

Explain the problem, reassure where appropriate and provide supportEncourage good sleep hygiene (see Chapter 4.14.2)Where possible treat the underlying cause of the sleep disturbance 
 (e.g. medical or psychiatric disorder)
Take safety or protective measures (e.g. for hazardous parasomnias)
Speciﬁ  c behavioural treatments for insomnia ( Chapter 4.14.2 )
Chronotherapy  (for circadian sleep-wake rhythm disorders)
  Sleep phase retiming
  Light therapy
Medication  Hypnotics (very selective and short-term)  Stimulants (narcolepsy)  Melatonin (for some circadian sleep–wake rhythm disorders)Physical measures  (e.g. for obstructive sleep apnoea)
  Continuous positive airway pressure (CPAP)
  Surgery (selected cases)

931
not necessarily accompanied by clinical manifestations. A prime 
example of this is the reduced time between onset of sleep and the start of the ﬁ  rst REM sleep period (‘REM latency’) in certain forms 
of severe depression. This can be viewed as a type of biological marker which may persist even after the depression itself has lifted, and which may also be seen in relatives of a depressed person with this PSG ﬁ  nding without they themselves suffering from depression. 
However, the basic signiﬁ  cance of reduced REM latency is, as yet, 
obscure and not helped by the fact that it has also been described in other psychiatric conditions, narcolepsy, following withdrawal from REM sleep-suppressing substances, during recovery from sleep deprivation, and a number of other diverse circumstances.
Another aspect of the pathophysiological relationship between 
sleep and mood which awaits clariﬁ  cation is a paradox that, while

sleep and mood which awaits clariﬁ  cation is a paradox that, while 
depression is usually associated with sleep disturbance and loss, sleep deprivation is reported to have an antidepressant effect in some patients although the effect does not persist beyond the 
period of depression.
Clinical sleep disorders associated 
with neurological and other medical illness
Of obvious relevance to psychiatric practice in general, but liaison 
psychiatry in particular, is the fact that disturbed sleep (often severe) is associated with many medical conditions. Main examples of this are shown in Table 4.14.1.4 together with mention of treat-ment issues in relation to each type of illness. Additional general considerations regarding treatment are as follows:
X The main emphasis in the management of sleep disorders in

this context should be placed on the treatment of the medical Table 4.14.1.3  Clinical sleep disturbance in psychiatric disorders
Psychiatric condition Likely/possible sleep problem/disorder Possible treatment issues/principles (see also text for general poin ts)
Depression General
Emphasis on treatment of depression
Possible sleep complications of ADs: drowsiness, insomnia (including SSRIs), 
RLS, PLMS, RBD
Insomnia Early treatment required to prevent worsening of depression
Sedating ADs may be helpful
EDS (minority) More stimulating ADs may be appropriate
Light therapy for SAD
Mania Profound insomnia Vigorous treatment required Mood-stimulating drugs may cause arousal disorders
Anxiety disorders Insomnia and disrupted (poor quality) sleep
PTSD nightmares
Nocturnal panic attacksIn addition to behavioural treatments; larger dose of antipsychotics at bedtime 
may be helpful

Eating disorders Insomnia (especially anorexia nervosa)
EDS (especially bulimia nervosa)
Sleepwalking with eating behavioursGeneral principles for insomnia (see Chapter 4.14.2)
Possibly SSRIs
See Chapter 4.14.4 for management of sleepwalking
Schizophrenia Insomnia Most neuroleptics promote sleep
As in other psychotic states, behavioural sleep treatments and sleep hygiene are important
Alcohol and other 
substance abuse (including 
withdrawal states)Insomnia including poor qualitysleep
Disrupted sleep-wake cycleAvoid sedative-hypnotic drugs 
Sleep hygiene principles (Chapter 4.14) and chronotherapy for sleep–wake cycle 
abnormalities
Alzheimer’s disease and 
other dementing disordersProgressive insomnia with fragmented sleep 
and sleep–wake cycle disorders including

and sleep–wake cycle disorders including 
nocturnal agitated wandering 
RBDGeneral principles for insomnia treatments; 
Sleep problems with some anti-dementia drugs 
Low-dose antipsychotics, if necessary
Promote day–night cues including regular experience of daylight; discourage daytime napping
Clonazepam
Child and adult ADHD Insomnia Stimulants can add to the sleep problem
KEY:
ADs  = Antidepressants
ADHD =  Attention-deﬁ  cit hyperactivity disorder
EDS   = Excessive daytime sleepinessPLMS    = Periodic limb movements in sleepRBD    = REM sleep behaviour disorderRLS   = Restless legs syndrome
SAD  = Seasonal affective disorder
SSRI    = Selective serotonin reuptake inhibitors4.14.1 basic aspects of sleep–wake disorders

SECTION 4  clinical syndromes of adult psychiatry 932
Table 4.14.1.4  Clinical sleep disturbance in neurological and other medical illness
Medical condition Likely/possible sleep problem/disorder Possible treatment issues/principles (see also text for general points)
Parkinson’s disease and/or 
related syndromesProgressive insomnia including poor quality sleep
Parasomnias (e.g. nightmares, nocturnal hallucinations)
EDS including sleep attacks
PLMS
RBDMainly behavioural treatment and sleep hygiene measures as in other 
insomnias (see Chapter 4.14.2)
Consider possible effects of anti-Parkinson’s medication on these and 
other sleep problemsPossibly daytime stimulants
Usual treatments for PLMS, if severe
Clonazepam usually effective
Epilepsy Disrupted sleep depending on type, cause, and severity
EDSSleep generally improves with seizure control
Sedating AEDs can be a factor
Stroke Insomnia
OSAUsual measures for insomnias
Head injury Effects depend on type and severity

Poor quality sleepOSA, EDSAvoid respiratory depressant substances
Usual measures for OSA (see Chapter 4.14.3)
Neuromuscular disease OSA, EDS As aboveTourette syndrome Disrupted sleep
SleepwalkingTreatment of tic disorder should improve sleep
Cardiovascular disease
 Congestive heart failure Central sleep apnoea, orthopnoea Some antihypertensive, hypolipidaemic and antiarrythmic drugs can 
cause insomnia
 Coronary heart disease Nocturnal angina Beta blockers can produce insomnia and nightmares
Respiratory disease
 COPD Nocturnal dyspnoea Hypnotics contraindicated in respiratory disease Asthma Nocturnal awakenings, EDS Theophylline can cause insomnia
Gastrointestinal disorders 
(peptic ulcer, reﬂ  ux oesophagitis)Nocturnal awakenings
Rheumatological disorders and 
other chronic pain conditions

other chronic pain conditions 
(including cancer)Insomnia, disrupted sleep, EDS Cortico-steroids and NSAI agents can disturb sleep 
Major analgesics have sedative effects 
Various anti-cancer drugs can disrupt sleep
Iron deﬁ  ciency PLMS
RLSTreat underlying condition
Endocrine disease
 Diabetes Awakenings from nocturnia or painful peripheral 
neuropathy
OSA
 Hyperthyroidism Insomnia Myxoedema OSA
Chronic renal failure Sleep disruption
EDSOSA
RLS and PLMSImprovement with haemodialysis
ICU patients Severe sleep disruption and deprivation including 
sleep–wake cycle disorders causing confusional and 
psychotic statesCause of reason for intensive care relevant, plus sleep disrupting effect 
of ICU environment, procedures and medications
Obesity OSA Complications of obesity (e.g. diabetes, joint diseases) affect sleep
KEY
AED    = Anti-epileptic drugs

KEY
COPD  = Chronic obstructive pulmonary diseaseEDS   = Excessive daytime sleepiness
ICU  = Intensive care unit
NSAI  = Non-steroidal anti-inﬂ  ammatory
OSA   = Obstructive sleep apnoeaPLMS = Periodic limb movements in sleepRBD  = REM sleep behaviour disorderRLS   = Restless legs syndrome

933
condition itself, although additional treatment for the sleep dis-
order may well be required.
X Treatment for other, co-morbid conditions may well be needed, 
in particular anxiety and depression which will have their own adverse effects on sleep.
X Hypnotic drugs should be used very sparingly (especially in
the elderly) because of their potential complications asdescribed in Chapter 6.2.2. In view of their respiratory-depressand effects, benzodiazepines in particular are contraindi-cated in sleep apnoea and in the presence of other severerespiratory disease.
X The possible effects on sleep of over-the-counter medications 
also need to be considered. Nasal decongestants and anorectics are stimulants and can cause insomnia. The same is true of caf-feine-containing drinks used as ‘energy boosters’ . Non-prescribed sleeping preparations (which usually contain anti-histamines) may well cause daytime drowsiness.
As mentioned earlier, the link between medical illness and sleep

As mentioned earlier, the link between medical illness and sleep 
disturbance may operate in the opposite direction. For example, chronic sleep loss or disruption is associated with the development of such chronic health problems as coronary artery disease or diabetes.
Kryger, M.H., Roth, T., and Dement, W.C. (eds.) (2005). Principles and 
practice of sleep medicine  (4th edn). Elsevier Saunders, Philadelphia, PA.
American Academy of Sleep Medicine. (2005). The international 
classiﬁ  cation of sleep disorders: diagnostic and coding manual  (2nd edn). 
American Academy of Sleep Medicine, Westchester, IL.
Colton, H.R. and Altevogt, B.M. (eds.) (2006). Sleep disorders and sleep 
deprivation: an unmet public health problem . National Academies Press, 
Washington, DC. Available from http.//www.nap.edu/catalog/11617 html
Shapiro, C. and McCall Smith, A. (eds.) (1997). Forensic aspects of sleep .

 1. Bonnet, M.H. (2005). Acute sleep deprivation. In Principles and
practice of sleep medicine  (4th edn) (eds. M.H. Kryger, T. Roth,
and W.C. Dement), pp. 51–6. Saunders, Philadelphia, PA.
 2. Dinges, D.F., Rogers, N.L., and Baynard, M.D. (2005). Chronic sleep 
deprivation. In Principles and practice of sleep medicine  (4th edn) 
(eds. M.H. Kryger, T. Roth, and W.C. Dement), pp. 67–76. W.B. Saunders, Philadelphia, PA.
 3. Stores, G. (2007). Clinical diagnosis and misdiagnosis of sleep
disorders (Review). Journal of Neurology, Neurosurgery, and Psychiatry ,
78, 1293–7.
 4. Buysse, D.J., Reynolds, C.F., Monk, T.H., et al. (1989) The Pittsburgh 
sleep quality index: a new instrument for psychiatric practice and research. Psychiatric Research ,28, 193–213.4.14.2 Insomnias

Most people’s experiences of poor sleep are memorable, because 
sleeplessness and its daytime consequences are unpleasant. There are those, however, for whom insomnia is the norm. Persistent and severe sleep disturbance affects at least one in 10 adults and one in ﬁ ve older adults, thus representing a considerable public health 
concern. Sleep disruption is central to a number of medical and

concern. Sleep disruption is central to a number of medical and 
psychiatric disorders, and insomnia is usually treated by general practitioners. Therefore differential diagnosis is important, and respiratory physicians, neurologists, psychiatrists, and clinical psychologists need to be involved. The purpose of this chapter is to summarize current understanding of the insomnias, their appraisal, and treatment. Particular emphasis will be placed upon evidence-based practical management.
Insomnia often remains unreported, and ﬁ  nally presents when a 
poor sleep pattern is well established. Alcohol has long been a ﬁ  rst-
line self-administered sleep aid, and recent years have seen an increasing use of ‘over-the-counter’ preparations and ‘self-help’ strategies. The clinical presentation is commonly of a frustrated patient, trapped in a vicious circle of anxiety and poor sleep, who reports having ‘tried everything’ .
(1,2)

(1,2)
There may be concern about the pattern of sleep. This is the most 
quantiﬁ  able aspect of self-report relating to, for example, length of 
time taken to fall asleep, frequency and duration of wakenings, or total amount of sleep. A poorly established sleep pattern can lead to unpredictability of what sleep will be like on any given night. Patients often report poor quality of sleep, and subjective perceived quality can be a critically important outcome variable. Typical reports relate to light sleep and sleep felt to be unrestorative. Although it may be unclear how such complaints relate to EEG sleep architecture, the clinician should not overlook qualitative report as it may reﬂ  ect underlying pathophysiology. Concerns are 
normally expressed also about the daytime effects of poor sleep. These can be cognitive effects, such as fatigue, sleepiness, inatten-tion, and some impairments in performance, or emotional effects, 
such as irritability and anxiety.
(2)

(2)
The International Classiﬁ  cation of Sleep Disorders  (second edition: 
ICSD-2 )(3) was published in 2005 and provides the most compre-
hensive account of sleep disorders, both for descriptive purposes and for differential diagnosis (see Chapter 4.14.1). ICSD-2 describes insomnias as disorders of initiating and maintaining sleep. Patients may have either sleep-onset problems or wakenings from sleep, or both of these. Table 4.14.2.1 summarizes the principal classi-ﬁ cations that relate to the insomnias, along with some other sleep 
disorders where patients commonly present with insomnia symptoms. As can be seen, concomitant symptomatology, potential aetiological factors, and sleeplessness require careful assessment in order to reach a valid diagnosis.4.14.2 insomnias

SECTION 4  clinical syndromes of adult psychiatry 934
Severity of insomnia is judged along dimensions of frequency, 
intensity, and duration, as well as impact on daytime functioning and quality of life. Generally, the criteria for severe and chronic insomnia are a minimum duration of 6 months with problems presenting three or more nights per week. Restlessness, irritability, anxiety, daytime fatigue, and tiredness commonly accompany such presentations.
(2) Mild and moderate insomnia may be diagnosed 
where problems are less intrusive.
Most patients presenting with insomnia have psychophysiologi-
cal difﬁ  culty initiating and/or maintaining sleep. Usually marked

cal difﬁ  culty initiating and/or maintaining sleep. Usually marked 
functional effects and somatized tension associated with sleep are evident. The patient reports extreme tiredness while being unable to sleep satisfactorily and appears preoccupied with sleep and its consequences. This contrasts, for example, with the circadian disorders where, in delayed sleep-phase type, the patient may not feel sleepy until late in the normal sleep period, and in advanced sleep-phase type, may waken early and be unable to return to sleep. Taking a history, incorporating screening questions on restlessness, limb movements, and breathing can help to diagnose obstructive sleep apnoea syndrome, periodic limb movement disorder, and 
restless legs syndrome, although full polysomnographic evaluation 
may also be required.
(4) However, polysomnography is not essential

(4) However, polysomnography is not essential 
for the diagnosis of insomnia, for which sleep diary monitoring (see Chapter 4.14.1) is usually the most useful form of assessment.
(2)
Wrist actigraphy is an inexpensive objective evaluation, which estimates sleep/wakefulness based upon body movement.
(5)
Continuous recordings can be made over 5 to 10 consecutive 24 h periods. It is useful in identifying paradoxical insomnia, and charted data can be inspected for circadian anomalies.
Other causes of insomnia are reported in Table 4.14.2.1 and 
should not be overlooked. In particular, insomnias due to a drug or substance can include hypnotic-dependent sleep disorder, asso-ciated most commonly with benzodiazepine (BZ) drugs where withdrawal leads to exacerbation of the primary problem.
(6) This

(6) This 
can be mistaken for a severe underlying insomnia and hencereinforce hypnotic dependency. Likewise, a wide range of psychiat-
ric conditions, particularly affective disorders, has associated sleep symptomatology (see Chapter 4.14.1). A primary diagnosis of psychophysiological insomnia cannot be made where diagnostic criteria for DSM-IV Axis I or Axis II disorders are fulﬁ  lled. However, 
it is very important to note that sleep disturbance often precedes depression. The bulk of the psychiatric epidemiological data indicate that insomnia is an independent risk factor for ﬁ  rst 
episode depressive illness, and for recurrence of depression, in adults of all ages.
(7,8) Insomnia should not be assumed to be simply

(7,8) Insomnia should not be assumed to be simply 
a symptom of underlying depression, even when depression is present. Unless the illness courses clearly co-vary it is best to make a diagnosis of co-morbid insomnia. Similar caveats apply to insomniaassociated with medical disorders, both in terms of identifying a primary illness, and concluding that insomnia has the status of an 
associated/ co-morbid disorder (see Chapter 4.14.1).
Insomnia affects one-third of adults occasionally, and 9 to 12 per cent on a chronic basis. It is more common in women, in shift workers, and in patients with medical and psychiatric disorders. Prevalence amongst older adults has been estimated at up to 25 per cent and sleepiness and hypnotic drugs are risk factors for injury and fracture.
(9) The decline in prescription of anxiolytics has

(9) The decline in prescription of anxiolytics has 
been greater than the rate of decline for hypnotics [taking BZ and benzodiazepine receptor agonists (BzRAs) together]. Furthermore, there is increasing use of (off-label) sedative anti-depressants primarily to treat insomnia.
Aetiology
Many patients report having been marginal light sleepers before developing insomnia.
(4) Sleep disturbance often arises during life 
change or stress, and such adjustment sleep disorder may represent a normal transient disruption of sleep. However, secondary factors, such as anxiety over sleep and faulty sleep–wake conditioning, may Table 4.14.2.1  The classiﬁ  cation and differential diagnosis of the insomnias within ICSD-2
Classiﬁ  cation Sleep disorder Essential features, complaint of insomnia plus
Insomnias Psychophysiological insomnia
Paradoxical insomniaIdiopathic insomnia
Insomnia due to a mental disorder
Inadequate sleep hygiene

Insomnia due to a medical disorderInsomnia due to drug or substance
Adjustment insomniaLearned sleep preventing associations, conditioned arousal, ‘racing mind’ phenomenon
Complaint of poor sleep disproportionate to sleep pattern and sleep duration
Insomnia typically begins in childhood or from birth
Course of sleep disturbance concurrent with mental disorder
Daily living activities inconsistent with maintaining good-quality sleep
Course of sleep disturbance concurrent with mental disorderSleep disruption caused by prescription medication, recreational drug, caffeine, alcohol or foodstuffPresence of identiﬁ  able stressor, insomnia resolves or is expected to resolve when stressor is removed
Sleep-related 
breathing disordersObstructive sleep apnoea syndrome 
Periodic limb movement disorder

Periodic limb movement disorder 
Restless legs syndromeExcessive sleepiness, obstructed breathing in sleep, associated symptoms include snoring and a 
dry mouthEpisodes of repetitive, highly stereotyped limb movements occurring in sleep
Strong, nearly irresistible urge to move legs relieved by walking
Circadian rhythm 
sleep disordersDelayed sleep phase type
Advanced sleep-phase typePhase delay of major sleep episode, initial insomnia, excessive sleepiness in morning
Phase advance of major sleep episode, inability to stay awake in evening, early wakening

935
exacerbate and maintain the insomnia as a chronic problem when 
sleep itself becomes a focus for concern. People with insomnia may be hyperaroused relative to normal sleepers, for example having higher levels of cortisol and ACTH, and also ﬁ  nd it difﬁ  cult to 
‘down-regulate’ their arousal at bedtime.
(2,10,11)
There has been little research on the natural course of insomnia. However, untreated psychophysiological insomnia can last for decades, and may gradually worsen over time. Indeed, there is a developmental trend for sleep pattern to deteriorate, with increas ing 
age. On the other hand, delayed sleep-phase syndrome and insufﬁ  -
cient sleep hygiene can be associated with lifestyle problems and may ameliorate as these are resolved. Although certain insomnias tend to persist if untreated, prognosis with effective treatment can 
be very good.
Treatment
A review of the evidence
(a) Drug therapy

Treatment
Traditionally, insomnia has been treated pharmacologically. Barbiturates were superseded by BZ compounds during the 1960s and 1970s. These drugs were safer in overdose, were thought to have fewer side effects, and to be less addictive . Controlled studies 
have demonstrated that a considerable number of BZ, of short to intermediate half-life, are effective hypnotic agents. However, from the mid-1970s potential problems became apparent, both during administration and withdrawal. Longer-acting hypnotics were prone to carry-over effects of morning lethargy, and shorter-acting drugs to ‘rebound insomnia’ .
(6) Furthermore, tolerance develops, 
leading either to increased dosing or switching to alternative medication. Although BZs used for short periods/intermittently can maintain effectiveness, these are not the treatment of choice in chronic insomnia,
(12) and are contraindicated in older adults and

(12) and are contraindicated in older adults and 
where insomnia may involve sleep-related breathing disorder because of their potentially depressant effects on respiration. A number of BZ compounds have been removed from the market in the United Kingdom, United States, and elsewhere.
Contemporary hypnotic therapy has extended to include BzRAs 
(often referred to as the ‘z’ drugs), and more recently melatonin receptor agonists (MeRAs) have been introduced. Whereas the place in therapeutics of MeRAs has yet to become established, the BzRAs are often thought to offer more sustained benefit for insomnia, and to have fewer adverse effects. Nevertheless, there remains uncertainty about the effectiveness of BzRAs in chronic insomnia.
(13)
(b) Psychological therapy

(13)
Psychological treatment for chronic insomnia, primarily in the form of cognitive behavioural therapy (CBT), has been extensively investigated in over 100 controlled studies during the past 20 years. Five meta-analyses and numerous systematic reviews have demonstrated that CBT is associated with large effect size changes (measured in standardized z scores) in the primary symptom 
measures of sleep latency (difﬁ  culty getting to sleep) and wake time 
after sleep-onset (difﬁ  culty remaining asleep).
(14,15) Around 70 per 
cent of patients with persistent sleep problems appear to beneﬁ  t from CBT and effects are maintained to long-term follow-up. It is

cent of patients with persistent sleep problems appear to beneﬁ  t from CBT and effects are maintained to long-term follow-up. It is 
thought that CBT achieves these outcomes because it tackles directly the dysfunctional thoughts and maladaptive behaviours that otherwise maintain insomnia. Recent controlled studies have shown that CBT may be effective in general practice settings with nurses delivering the intervention according to a standard protocol.
(16,17) Despite the superior efﬁ  cacy of CBT relative to 
medication for insomnia, and these recent demonstrations of CBT working in real-world settings, practical problems remain in making CBT widely available.
Within the CBT model, a number of strategies have strong 
empirical support. Behavioural procedures such as stimulus control and sleep restriction, and cognitive strategies such as para-doxical intention and thought restructuring have been extensively investigated

(2,14,15) and are outlined brieﬂ  y below.
(c) Melatonin, light therapy, and exercise
The pineal hormone melatonin has been the subject of highly 
publicized claims. However, scientiﬁ  c research has been limited. 
Several controlled studies support its sleep-promoting effects, but the use of melatonin continues to be controversial. At best it may be useful as a chronobiotic for reducing sleep latency.
(18) Several 
MeRA products are currently under formal evaluation, so more 
data may be available soon.
Bright light is a potent marker for human circadian rhythms, 
and has been known for some time to enable the resetting of 
such rhythms in advanced sleep-phase syndrome and delayed 
sleep-phase syndrome.(19) The results of studies investigating the 
efﬁ cacy of bright light against psychological treatments for psycho-
physiological insomnia are awaited. A limiting factor to the value of light therapy is that continued treatment may be required to maintain therapeutic effects.

Athletic people sleep well, although this may be more to do with 
behavioural patterning than aerobic ﬁ  tness. Nevertheless, there is 
evidence that exercise can have positive effects upon sleep quality, particularly if taken late afternoon or early evening, and in other-wise relatively ﬁ  t individuals.
(20) Morning exercise can also be an 
effective modality to encourage the same waking time and early morning light exposure; which help to reset sleep patterns on a daily basis.
(a) General perspective

Non-pharmacological treatment using CBT procedures should be preferred over pharmacological treatment, in cases of severe persis-tent insomnia. Hypnotic agents should be recommended mainly for short-term or occasional use, although longer-term trial data are now becoming available. The practitioner should be aware of morning-after effects, and potential problems of withdrawal and dependency, not only with BZs but also possibly with BzRAs. Psychological intervention may also facilitate reduction or discon-tinuation of medication in hypnotic-dependent person with insomnias.
(21) There is limited support for the use of melatonin 
or exercise as treatments of choice, although light therapy seems effective for circadian disorders.
(b) Using cognitive behavioural therapies

Brief descriptions of effective management strategies are presented in Tables 4.14.2.2 and 4.14.2.3. The following text provides 4.14.2 insomnias

SECTION 4  clinical syndromes of adult psychiatry 936
explanation of underlying psychological models and further 
information on implementation.
(i) Sleep education and sleep hygiene
The simple provision of information ameliorates the sense of being out of control. Inaccurate attributions are challenged and misunderstandings corrected by understanding what sleep is, how ommon insomnia can be, how sleep changes with age, good sleep hygiene practices, and some facts about sleep loss. Similarly, sleep hygiene provides patients with a starting point for self-management. These techniques are best construed as introductory 
but they will not of themselves treat insomnia effectively.
(ii) Stimulus control treatment

Stimulus control increases the bedroom’s cueing potential for sleep. For good sleepers, the pre-bedtime period and the stimulus envi-ronment trigger positive associations of sleepiness and sleep. For the poor sleeper, however, the bedroom triggers associations with restlessness and lengthy night-time wakening via a stimulus-response relationship, thereby continuing to promote wakefulness and arousal. The model is similar to phobic conditions where a conditioned stimulus precipitates an anxiety response.
Treatment involves removing from the bedroom all stimuli which 
are potentially sleep-incompatible. Reading and watching televi-sion, for example, are conﬁ  ned to living rooms. Sleeping is excluded 
from living areas and from daytime, and wakefulness is excluded from the bedroom. The individual is instructed to get up if not asleep within 15–20 min or if wakeful during the night.

from living areas and from daytime, and wakefulness is excluded from the bedroom. The individual is instructed to get up if not asleep within 15–20 min or if wakeful during the night. 
Conceptually, stimulus control is a reconditioning treatment 
which forces discrimination between daytime and sleeping environments.
(iii) Sleep restriction therapy
Sleep restriction restricts sleep to the length of time which the person is likely to sleep. This may be equivalent to promoting ‘core sleep’ at the expense of ‘optional sleep’ . Sleep restriction primarily aims to improve sleep efficiency. Since sleep efficiency is the ratio of time asleep to time in bed, it can be improved either by increasing the numerator (time spent asleep) or by reducing the denominator (time spent in bed). People with insomnia generally seek the former, but this may not be necessary, either biologically or psychologically. Sleep restriction ﬁ  rst involves recording in a

sleep diary and calculating average nightly sleep duration. The aim, then, is to obtain this average each night. This is achieved by setting rising time as an ‘anchor’ each day and delaying going to bed until a ‘threshold time’ which permits this designated amount of sleep. Thus, the sleep period is compressed and sleep efﬁ  ciency is likely 
to increase. The permitted ‘sleep window’ can then be titrated 
week-by-week in 15 increments in response to sleep efﬁ  ciency 
improvements.
(iv) Cognitive control
This technique aims to deal with thought material in advance of bedtime and to reduce intrusive bedtime thinking. The person with insomnia is asked to set aside 15 to 20 min in the early evening to rehearse the day and to plan ahead for tomorrow; thus putting the day to rest. It is a technique for dealing with unﬁ  nished

business and may be most effective for rehearsal, planning, and self-evaluative thoughts which are important to the individual and which, if not dealt with, may intrude during the sleep-onset period.
(v) Thought suppression
Thought-stopping and articulatory suppression attempt to inter-rupt the ﬂ  ow of thoughts. No attempt is made to deal with thought 
material per se  but rather to attenuate thinking. With articulatory 
suppression the patient is instructed to repeat, subvocally, the word ‘the’ every 3 s. This procedure is derived from the experimental psychology literature. Articulatory suppression is thought to occupy the short-term memory store used in the processing of Table 4.14.2.2  Summary description of sleep hygiene and education 
components for the treatment of chronic insomnia
Components of sleep education
The need for sleep and its functionsSleep patterns across the lifespan
Sleep as a process with stages/phases

Factors adversely affecting steepThe effects of sleep lossThe concept of insomniaMeasuring sleep and sleep problems
Components of sleep hygiene treatment
Bedroom comfortable for sleep
Regular exercise, timing, and ﬁ  tness
Stable and appropriate dietUndesirable effects of caffeine and other stimulantsModeration of alcohol consumptionOther common ‘self-help’ strategies
Table 4.14.2.3  Summary description of cognitive behavioural 
Components of stimulus control and sleep restriction treatment
Deﬁ  ne individual sleep requirementsEstablish parameters for bedtime period (threshold time and rising time)Eliminate daytime nappingDifferentiate rest from sleep
Schedule sleep periods with respect to needs

Establish 7 day per week complianceRemove incompatible activity from bedroom environmentRise from bed if wakeful (>20 min)Avoid recovery sleep as ‘compensation’Establish stability from night to nightAdjust the sleep period as sleep efﬁ  ciency improves
Components of cognitive intervention
Identify thought patterns and content that intrudeAddress (mis)attributions connecting sleep and waking lifeEstablish rehearsal/planning time in early evening
Relaxation and imagery training
Distraction and thought blockingDevelop accurate beliefs/attributions about sleep and sleep lossChallenge negative and invalid thoughtsEliminate ‘effort’ to control sleepMotivate to maintain behaviour and cognitive changeUtilize relapse-prevention techniques

937
information. The type of material most likely to respond is repeti-
tive but non-affect-laden thoughts, not powerful enough to demand attention. Additionally, this technique may be useful during the night to enable rapid return to sleep.
(vi) Imagery and relaxation

There is a wide range of relaxation methods including progressive relaxation, imagery training, biofeedback, meditation, hypnosis, and autogenic training, but little evidence to indicate superiority of any one approach. Furthermore, there is little evidence to support either the presumption that people with insomnia are hyperaroused in physiological terms, or that relaxation has its effect through autonomic change. At the cognitive level, these techniques may act through distraction and the promotion of mastery. During relax-ation, the mind focuses upon alternative themes such as visualized images or physiological responses. In meditation the focus is upon a ‘mantra’ and in self-hypnosis upon positive self-statements. Relaxation may be effective for thought processes that are anxiety-based, confused, and which ﬂ  it from topic-to-topic.
(vii) Cognitive restructuring
Cognitive restructuring challenges faulty beliefs which maintain

Cognitive restructuring challenges faulty beliefs which maintain 
wakefulness and the helplessness which many people with insom-nia report. It appears to work through appraisal by testing the validity of assumptions against evidence and real-life experience. As an evaluative technique, it may be effective with beliefs that are irrational but compelling. If such thoughts, for example ‘I am going to be incapable at work tomorrow’ , are not challenged, they will create high levels of preoccupation and anxiety and sleep is unlikely to occur. With cognitive restructuring, the person with insomnia learns alternative responses to replace inaccurate thinking.
(viii) Paradoxical intention

Finally, the technique of paradoxical intention is useful in situa-tions where performance anxiety has developed, that is, where the effort to produce a response inhibits that response itself. The para-doxical instruction is to allow sleep to occur naturally through passively attempting to remain quietly wakeful rather than attempt-ing to fall asleep. Paradox may be regarded as a decatastrophizing technique since it appears to act upon the ultimate anxious thought (of remaining awake indeﬁ  nitely) initially by focusing on and 
enhancing this thought (a habituation model) and then subjecting it to appraisal through rationalization and experience. By intend-ing to remain awake, and failing to do so, the strength of the sleep drive is re-established, and performance effort is reduced.
There is insufﬁ  cient knowledge of the natural course of transient

There is insufﬁ  cient knowledge of the natural course of transient 
sleep disorders. Mention has been made of adjustment sleep disor-der and of the association of life events and stressors with the onset of insomnia. Systematic research is required to establish the ‘setting conditions’ for the secondary maintenance of insomnia beyond an initial normative reaction to events. Perhaps there is an interaction with a predisposing tendency to light sleep, or with introspection and worry. The instinct to increase opportunity to sleep (spend longer in bed to catch up) when insomnia symptoms develop should probably be resisted. If anything it may be better to advise patients to limit sleep opportunity so that their pattern knits together again more quickly.The establishment and maintenance of a regular ‘tight’ routine,

both pre-bedtime and in terms of sleep schedule, seem to be impor-tant preventive factors. Such chronobehavioural functioning can be at risk of disruption by, for example, jet lag, shift work, weekend patterns differing from weekday, adolescent lifestyle, and retirement. Adherence to, and/or reinstatement of, an adaptive pattern seems crucial.
It is important not to underestimate the importance of attitudes 
and beliefs in the presentation of insomnia. Exaggerated or emotionally and mentally arousing thoughts should be dealt with promptly. Sleep loss can be distressing, but patients should be reminded that nature seeks to restore equilibrium. What they need to do is to provide the conditions under which sleep can occur 
rather than attempt directly to control the sleep process.

rather than attempt directly to control the sleep process. 
Expectations are important also, since it is the breach of these which generally give rise to anxiety and dysfunctional beliefs about sleep requirements. More often than not sleep-related expectations are unrealistic and require reappraisal, even more so in older adults.
Finally, prevention should be extended to the known extrinsic 
causes of certain sleep disorders. Where alcohol, stimulants, or proprietary drugs interfere with sleep and the recovery of the normal sleep process, attention should be paid to these factors. Better still, patients should be encouraged to seek advice early rather than go down the path of self-administered treatment. Avoiding the use of hypnotic agents, both in general practice and during acute admissions to hospital, would substantially reduce the number of iatrogenic cases of chronic insomnia.
Espie, C.A. (2006). Overcoming insomnia and sleep problems: a self-help

Espie, C.A. (2006). Overcoming insomnia and sleep problems: a self-help 
guide using cognitive behavioral techniques . Constable & Robinson Ltd, 
London [ISBN13: 978-184529-070-2/ ISBN10: 1-84529-070-4].
Perlis, M.L. and Lichstein, K.L. (2003). Treating sleep disorders: principles and 
practice of behavioral sleep medicine . John Wiley & Sons, Inc. Hoboken, 
NJ [ISBN0-47-44343-3].
Morin, C.M., Bootzin, R.R., Buysse, D.J., et al. (2006). Psychological and 
behavioural treatment of insomnia. Update of the recent evidence (1998–2004) prepared by a Task Force of the American Academy of Sleep Medicine. Sleep ,29, 1398–414.
Morin, C.M. and Espie, C.A. (2003). Insomnia: a clinical guide to assessment 
and treatment . Kluwer Academic/ Plenum Publishers, New Y ork 
[ISBN 0-306-47750-5].
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 2. Morin, C.M. and Espie, C.A. (2003). Insomnia: a clinical guide to 
assessment and treatment . Kluwer Academic/Plenum Publishers, 
New Y ork.
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AASM, Westchester, IL.
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polysomnography in the evaluation of insomnia. Sleep ,18, 58–70.
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342–92.
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among elderly community subjects: a systematic review and meta-analysis. The American Journal of Psychiatry ,160, 1147–56.
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persistence and treatment of sleep disorder in adults. Annual Review of 
Psychology ,53, 215–43.
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pathophysiology of insomnia. In The principles and practice of sleep 
medicine  (4th edn) (eds. M.H. Kryger, T. Roth, and W.C. Dement), 
pp. 714–25. W.B. Saunders, Philadelphia.

12. NIH. (2005). State-of-the-science conference statement on manifestations 
and management of chronic insomnia in adults . National Institutes 
of Health, Vol. 22, Number 2. Natcher Conference Center, Bethesda 
Maryland, USA.
13. NICE. (2004). Guidance on the use of zaleplon, zolpidem and zopiclone 
for the short-term management of insomnia . T echnology Appraisal 
Guidance No.77. National Institute for Clinical Excellence, London.
14. Smith, M.T., Perlis, M.L., Park, A., et al. (2002). Behavioral treatment 
vs pharmacotherapy for insomnia—a comparative meta-analysis. The
American Journal of Psychiatry ,159, 5–11.
15. Morin, C.M., Bootzin, R.R., Buysse, D.J., et al. (2006). Psychological

15. Morin, C.M., Bootzin, R.R., Buysse, D.J., et al. (2006). Psychological 
and behavioural treatment of insomnia. Update of the recent evidence (1998–2004) prepared by a Task Force of the American Academy of Sleep Medicine. Sleep ,29, 1398–414.
16. Espie, C.A., Inglis, S.J., T essier, S., et al. (2001). The clinical effectiveness 
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Research and Therapy ,39, 45–60.
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of General Practice ,53, 923–8.
4.14.3 Excessive sleepiness
Excessive sleepiness is not an homogeneous concept. It can manifest

Excessive sleepiness is not an homogeneous concept. It can manifest 
itself as bouts of sleepiness, irresistible and refreshing sleep episodes, abnormal lengthening of night sleep with a major difﬁ  -
culty waking up in the morning or at the end of a nap or even periods of a week or so of almost continuous sleep recurring at 
several months’ intervals.
According to the recent second edition of the International 
Classiﬁ  cation of Sleep Disorders  (ICSD -2),
(1) disorders of excessive 
sleepiness are distributed within three chapters: sleep-related breathing disorders, hypersomnias of central origin not due to a circadian rhythm sleep disorder, sleep-related breathing disorders, or other cause of disturbed nocturnal sleep, and circadian rhythm sleep disorders.
However in this volume aimed at psychiatrists, the presenta-

tion of disorders of excessive sleepiness will obey another logic. Following “Generalities” including epidemiology, morbidity, clini-cal work-up, and laboratory tests, the various aetiologies will be presented according to the following six subchapters:
X Hypersomnia not due to substance or known physiological con-
dition (non-organic hypersomnia or psychiatric hypersomnia)
X Hypersomnia due to drug or substance
X Behaviourally induced insufﬁ  cient sleep syndrome
X Hypersomnia in the context of sleep-related breathing disorders
X Hypersomnias of central origin
X And the special case of delayed sleep phase syndrome.
Contrary to common thinking, excessive sleepiness is neither 
exceptional nor rare. Epidemiological surveys generally agree on a ﬁ gure of severe sleepiness (daily and embarrassing) in 5 per cent of 
the general population and of moderate sleepiness (occasional) in another 15 per cent.

(2) Interestingly, only a fraction of these 
subjects are aware of their condition, due to the fact that they pro-gressively lose reference to a normal state of alertness. As a conse-quence many subjects will not consult their physician for excessive sleepiness but will be brought to him by the spouse, worried about his or her falling asleep repeatedly in the middle of the day, or even referred by the company’s doctor due to unexplained car accidents or poor work efﬁ  ciency.
Morbidity
Excessive sleepiness has a severe impact on the life of patients.

Morbidity
Excessive sleepiness has a severe impact on the life of patients. 
Nearly half of the patients with excessive sleepiness report automo-bile accidents. Many have lost jobs because of their sleepiness. In addition, sleepiness is disruptive of family life. Cognitive func-tion is also impaired by sleepiness. In children excessive sleepiness has been associated with learning disability and in adults memory problems are frequent.
Clinical work-up and laboratory tests
Whatever the circumstance of the ﬁ  rst visit, the patient should be 
interviewed on the history of excessive sleepiness, the type and severity of it, the associated symptoms, the familial and occupa-tional consequences, the past and current treatments, and the personal and familial medical past-history.
In addition, the subject will complete a self-administered behav-
ioural scale, the Epworth sleepiness scale. This scale asks the subject to rate the probability of dozing from 0 (would never doze) to

939
3 (high chance of dozing) in eight more or less soporiﬁ  c daily situ-
ations. A score of over 10 is taken to indicate abnormal sleepiness.
The subject will then undergo a physical and psychological 
examination.
Laboratory tests will be chosen according to the clinical 
impression.
The most frequently used test is the multiple sleep latency test
(MSLT). The test was developed on the basis of the following principle. The sleepier the subject, the faster he falls asleep. The test is based on 20 min polygraphic recordings (EEG, EOG, EMG) repeated every 2 h (four or ﬁ  ve times a day) starting 2 h about after 
morning awakening. The global sleepiness index is provided by the mean latency to sleep in the four or ﬁ  ve tests. A sleep laboratory 
of less than 5 min indicates pathologic sleepiness, a sleep latency from 10 to 20 min is considerd as normal, and latencies falling between the normal and the pathological values are considered as a diagnostic grey area.

Another test, the maintenance of wakefulness test  (MWT), is a 
variant of the MSLT. It was designed to evaluate treatment efﬁ  ciency 
in patients with excessive sleepiness. The major difference with the MSLT is in the instruction given to the test subject. The subject being tested is told to attempt to remain awake. The subject is seated in comfortable position in bed, as opposed to lying down in the MSLT, with low lighting behind him (7.5 W at 1 m). Speciﬁ  c recom-
mendations include using a four-trial, 40 min version of the MWT. A mean sleep latency of less than 8 min on the 40 min MWT is abnor-mal and scores between 8 and 40 min are of uncertain signiﬁ  cance.
Prolonged polysomnographic recordings , obtained by either tradi-
tional laboratory polysomnographic monitoring or ambulatory recordings, provide a good picture of the actual time asleep within the 24 h period. However, this procedure is neither validated nor standardized.

In addition, whenever there is some doubt about the possibility 
of hypersomnia associated with a psychiatric disorder, a psycho-
metric /psychiatric evaluation  will be performed.
Aetiology and treatment
Hypersomnia not due to substance or known 
physiological condition
It explains about 5 to 7 per cent of cases of hypersomnia seen in 
sleep disorders centres. Women are more susceptible than men.
Excessive daytime sleepiness is reported. Subjects show an elevat-
ed score on the Epworth sleepiness scale. Night sleep is perceived as non-restorative and generally of poor quality. Patients are often 
intensely focused on their hypersomnia, and psychiatric symptoms 
typically become apparent only after prolonged interview or psy-
chometric testing. Poor work attendance, abruptly leaving work because of a perceived need to sleep are common. Polysomnography 
typically shows a prolonged sleep latency, an increased wake time 
after sleep onset, and a low sleep efﬁ  ciency. REM latency may be

after sleep onset, and a low sleep efﬁ  ciency. REM latency may be 
shortened in the case of bipolar disorder. Contrasting with the elevated score on the Epworth sleepiness scale, sleep latency on the 
MSLT is often within normal limits. A 24 h continuous sleep record-
ing typically shows considerable time spent in bed during day and night, a behaviour referred to as clinophilia, from the Greek κλινη
(bed) and ϕιλεω  (love).
Psychiatric interview is essential to diagnose the underlying 
condition. Causative psychiatric conditions include bipolar type II disorder, dysthymic disorder, undifferentiated somatoform disorder, 
adjustment disorder, or personality disorder.
Conventional drugs such as antidepressants or anxiolytics are 
often insufﬁ  cient. Modaﬁ  nil, an awakening drug given at a daily 
dose of 100 to 200 mg, is usually active.
In the group of psychiatric disorders a separate place should be

In the group of psychiatric disorders a separate place should be 
reserved to seasonal affective disorder remarkable for episodes of 
major depression occurring only during the winter months, associ-
ated with fatigue, loss of concentration, increased appetite for carbohydrates, weight gain, and increased sleep duration. Morning bright light treatment (2500 lux for 2 h) is efﬁ  cient.
Hypersomnia due to drug or substance
A wide spectrum of medications used in psychiatry may be respon-
sible for excessive sleepiness.
(a) Anxiolytics and hypnotics
Benzodiazepines have sedative effects, but these effects vary with dose, administration (single or repeated dose), age, and state of the subject (normal, anxious, or depressed). Non-benzodiazepines usually induce limited sleepiness only.
(b) Antidepressants

Tricyclic antidepressants have sedative properties depending on the molecule, dose, and the subject to whom they are administered. SSRI can also induce sleepiness with high within-patient variability. Venlafaxin, a serotonine, and norepinephrine reuptake blocker may induce excessive sleepiness.
(c) Neuroleptics
The degree of sedation varies widely from subject to subject. Empirically, three-fourth of the patients treated with neuroleptic phenothiazines experience sleepiness in a dependent manner. Among the newer agents clozapine is the most sedating drug, followed by olanzapine and quetiapine. Risperidone and sertindole are less sedating drugs.
Behaviourally induced insufﬁ  cient sleep syndrome
According to ICSD-2, this syndrome occurs when an individual 
persistently fails to obtain the amount of sleep required to main-tain normal levels of alertness. Behaviourally induced insufﬁ  cient

persistently fails to obtain the amount of sleep required to main-tain normal levels of alertness. Behaviourally induced insufﬁ  cient 
sleep syndrome is likely the most common cause of daytime sleepi-ness. In a population-based study conducted in Japan among 3030 subjects aged 20 years and older, 29 per cent slept less than 6 h per night, and 23 per cent reported having insufﬁ  cient sleep.
(3) The

(3) The 
syndrome is likely to be widespread in truck drivers, working mothers, family doctors, executives, and students. The main symp-toms are excessive sleepiness in the afternoon or early evening, decrease of diurnal performances, and, of interest to the psychia-trist, irritability, nervousness, and depression. Diagnosis of the syndrome is relatively easy provided that a thorough interview is conducted. The most rational treatment is an increase of daily total sleep time, either by spending more time in bed at night, or by taking one or two naps per day.
Hypersomnia in the context of sleep-related 
breathing disorders
The most frequent condition among these disorders is the obstruc-
tive sleep apnoea syndrome. This syndrome was ﬁ  rst described by 4.14.3 excessive sleepiness

SECTION 4  clinical syndromes of adult psychiatry 940
Guilleminault et al .(4) It is most frequent in 50-year-old males. 
According to Y oung et al .(5) the prevalence of obstructive sleep 
apnoeas accompanied by excessive daytime sleepiness in North America is 4 per cent in men and 2 per cent in women.
Clinical features include night-time and daytime symptoms. 
Night-time symptoms are represented by loud snoring, apnoeic episodes ending with sonorous breathing resumption, nocturia, severe fatigue upon awakening, and sometimes headache. Daytime symptoms are dominated by excessive sleepiness, which varies in intensity among patients. Other symptoms include irritability, negligence, loss of concentration, loss of libido, impotence, and sometimes depression.
Patients are often obese or mildly obese. High blood pressure is a

Patients are often obese or mildly obese. High blood pressure is a 
frequent feature. The ear, nose, and throat examination usually reveals a narrow upper airway due to close-set posterior tonsillar pillars, an abnormally long and hypot onic soft palate, a hypertrophic 
uvula, or macroglossia.
The positive diagnosis rests on polysomnography allowing the 
observation of nocturnal disrupted sleep and the identiﬁ  cation of 
apnoeas and of their type (obstructive, central, or mixed) as well as their consequences on heart rate, oxygen desaturation, and degree of somnolence.
Of note, some subjects do not have apnoeas or hypopnoeas
but increasing respiratory effort resulting in respiratory effort-
related arousals (RERAs) and are believed to be as much atrisk for complications. This state is most accurately identiﬁ  ed
with a quantative measurement of airflow and oesophageal manometry.
Obstructive sleep apnoea patients are at risk for systemic hyper-

tension, occasional arrhythmias and conduction disturbances, cardiac or cerebral ischaemia, functional cognitive impairment, and depression. In a multicentre telephone survey carried-outin 1994–1999 in ﬁ  ve European countries, among 18 980 subjects 
aged 15 to 100 years, 18 per cent of the individuals receiving adiagnosis of major depression also had a sleep-related breathing disorder and 17.6 per cent of the individuals receiving a diagnosis of sleep-related breathing disorder also had a diagnosis of major depression.
(6)
There are several possible approaches to treatment:
X Weight loss may be beneﬁ  cial. Avoidance of alcohol and sedatives 
should be recommended in all cases.
X Continuous positive airway pressure (CPAP) at night is the 
most widely used treatment. Good compliance requires proper preparation for the patient and an adaptation period.

X Oral appliances are suitable in mild obstructive sleep apnoea 
syndrome.
X Surgery consists mainly in nasal reconstruction in case of 
symptomatic airway blockade caused by bony, cartilaginous, or hypertrophied tissues that interfere with nasal breathing during sleep.
Hypersomnias of central origin
(a) Narcolepsy
First described in 1877(7) and given its name by Gelineau in 1880,(8)
narcolepsy is now distinguished into three entities, narcolepsy with cataplexy, narcolepsy without cataplexy, and narcolepsy due to medical condition.(i) Narcolepsy with cataplexy
Narcolepsy with cataplexy is not an exceptional condition. 
According to most recent evaluations its prevalence is 0.20 to 0.40 per 1000, i.e. slightly less than the prevalence of multiple sleep sclerosis.

Narcolepsy with cataplexy is characterized by two cardinal 
symptoms, excessive daytime sleepiness/irresistible sleep episodes and cataplexy, and other clinical features that are not necessarily part of the actual clinical picture.
Excessive sleepiness occurs daily. It comes in waves of varying

Excessive sleepiness occurs daily. It comes in waves of varying 
degree of severity, depending on the individual, building up into irresistible and refreshing episodes of sleep. Excessive sleepiness is brought on by passive situations such as watching TV , being a passenger in a car, or attending a lecture. However it can also awkwardly occur in unexpected situations such as eating, walking, swimming, or driving a car. Excessive sleepiness may lead to automatic behaviour, such as saying totally inappropriate words or sentences, arranging objects in unlikely places, or driving a vehicle to an unintended destination.
Cataplexy is the most speciﬁ  c symptom. It consists of a sudden 
bilateral loss of voluntary muscle tone with preserved conscious-
ness. It is triggered by environmental factors which are usually 
positive, such as a ﬁ  t of laughter, receiving a compliment, humour

positive, such as a ﬁ  t of laughter, receiving a compliment, humour 
expressed by the subject himself, the sight of prey for the hunter, the perception of a ﬁ  sh biting at the hook for the angler, a well-
caught ball at tennis, or by anger, but almost never by stress orfear. All the striated muscles may be affected except the extra-ocular and respiratory musculature, leading to the progressive slackening of the whole body. More often however the attack ispartial, involving certain muscles only, for example the jaw muscles, producing sudden difﬁ  culty in articulating words; the facial mus-

cles, responsible for a grimace; or the thigh muscles, causing a brief unlocking of the knees. Consciousness is maintained during the episode. Cataplexy varies in duration from a split second to several minutes. Attack frequency varies from only a few per year, or even less, to several per day. In rare cases, especially after abrupt with-drawal of antidepressant medication, episodes of cataplexy may repeat themselves for minutes or hours, a state referred to as “status cataplecticus” .
The other clinical features are deemed accessory to the extent 
that they are not indispensable for diagnosis.
Hallucinations, whether hypnagogic (at the onset of sleep) or 
hypnopompic (on awakening), are vivid perceptual experiences, not dreams, either visual, or auditory or kinetic. Patients may perceive someone entering and walking in the room, ﬁ  nd them-
selves ﬂ  ying through the air or falling from a skyscraper. In some

selves ﬂ  ying through the air or falling from a skyscraper. In some 
cases of unrecognized narcolepsy with daytime hypnagogic/hypnopompic hallucinations, the patient may be mistakenly diag-
nosed as having a delusional psychosis.
Sleep paralysis is a sudden inability to move during the transi-
tion from sleep to wakefulness or vice versa, while the subject is conscious. It is often accompanied by hypnagogic hallucinations. It is very unpleasant. In narcoleptic patients sleep paralysis may last up to 10 min.
Nocturnal sleep disruption occurs in approximately 50 per cent 
of cases, depending on age and the time elapsed since the onset of condition. The patient typically falls asleep as soon as he gets to bed, but his sleep is disturbed by recurring awakenings. He may complain of disturbing dreams.

941
REM-sleep behaviour disorder is frequent, either as a mere poly-
somnographic ﬁ  nding, excess of muscle tone or phasic EMG 
twitching activity during REM sleep, or as clinically signiﬁ  cant 
complaint manifesting itself as an attempted enactment of dis-tinctly altered, unpleasant, action-ﬁ  lled, and violent dreams in 
which the individual is being confronted, attacked, or chased by unfamiliar people. Periodic limb movements in sleep are more fre-quent than in normal subjects.
Physical examination is normal except for a frequently increased 
body mass index, especially in children at the onset of the condition. Noteworthy is the abolition of deep tendon reﬂ  exes during a cata-
plectic attack.
In a majority of cases, excessive daytime sleepiness is the ﬁ  rst 
symptom to appear. In some patients, cataplexy occurs at the same time as excessive daytime sleepiness, but more often is delayed by one or several years. It is extremely rare for cataplexy to be the ﬁ  rst

clinical manifestation of narcolepsy with cataplexy.
The clinical diagnosis is based on clinical features. However, 
additional tests are highly recommended to conﬁ  rm the diagno-
sis. The ﬁ  rst test is polysomnography followed by an MSLT. At 
night a sleep onset REM period (SOREMP) is highly speciﬁ  c. It is 
observed in 25 to 50 per cent of cases. An increase in the amount 
of stage 1 NREM sleep and repeated awakenings are frequent 
ﬁ ndings. The MSLT shows a mean sleep latency of less than 8 min 
and two or more  SOREMPs. However, some patients, especially in 
middle or old age, with clear-cut excessive daytime sleepiness and cataplexy, may have only one SOREMP , or even none during the MSLT procedure.
T oday a CSF level of hypocretin-1 below 110 pg/mL is recognized 
as highly speciﬁ  c and sensitive for narcolepsy with cataplexy. 
However, up to 10 per cent of narcolepsy with cataplexy patients have normal levels of hypocretin-1.

There is no set pattern of evolution across patients. Excessive 
daytime sleepiness and irresistible episodes of sleep persist through-out life, but may diminish with age in some subjects. Cataplexy may spontaneously diminish with time or even totally disappear in some patients.
Narcolepsy is a very incapacitating disease. It interferes with 
every aspect of life. Education, performance at school and workplace, driving capability, recreational activities, interpersonal relationships, sexual life, and self-esteem. Depression is a frequent consequence of narcolepsy.
The mainstay of treatment is pharmacological although taking 
naps alleviates excessive sleepiness and refraining from emotion may prevent cataplexy.
Modaﬁ  nil is the ﬁ  rst-line treatment of excessive daytime sleepi-

ness and irresistible episodes of sleep. Methylphenidate is less used today. Based on several large randomized controlled trials showing the activity of sodium oxybate on excessive daytime sleepiness and 
irresistible episodes of sleep, there is a growing practice in the

irresistible episodes of sleep, there is a growing practice in the 
United States to use it for the later indications. However, adverse effects including nausea, nocturnal enuresis, confusional arousals, malaise, and headache are not exceptional. Sodium oxybate is the only registered treatment for cataplexy. Other treatments are antidepressants, including tricyclics, selective serotonion reuptake inhibitors (SSRIS) and more recently new antidepressants such as venlafaxine or atomoxetine, the later being increasingly used despite few or non-randomized placebo-controlled clinical trials. As for disturbed nocturnal sleep the most widely used treatmentis still hypnotics. However, the same randomized controlled trials 
have shown the activity of sodium oxybate against disturbed noc-turnal sleep.
(ii) Narcolepsy without cataplexy

Narcolepsy without cataplexy is described as excessive daytime sleepiness and irresistible episodes of sleep unaccompanied by cataplexy. Automatic behaviour may be present as may hypna-gogic hallucinations or sleep paralysis. Nocturnal sleep is usually less disturbed than in narcolepsy with cataplexy. When thesubject is young, cataplexy may develop later in the course of the disorder.
Given the risk of overdiagnosing, a positive diagnosis of narco-
lepsy without cataplexy cannot be done without an all-night poly-somnography followed by an MSLT documenting a mean sleep latency of less than 8 min and two or more SOREMPs.
(iii) Narcolepsy due to medical condition
As in the two previous categories, the patient has a complaint of excessive daytime sleepiness occurring almost daily for at least 3 months. However, the distinct featur e of this subtype of narcolepsy

is the existence of a signiﬁ  cant underlying medical or neurological 
disorder accounting for the excessive daytime sleepiness and/or cataplexy.
According to the ICSD -2 the diagnosis of narcolepsy due to med-
ical condition can be made only if one of the following is observed:
X a deﬁ  nite history of cataplexy
X a polysomnographic monitoring followed by an MSLT demon-
strating a mean sleep latency of less than 8 min with two or more SOREMPs
X hypocretin-1 levels in the CSF lower than 110 pg/ml, provided 
the patient is not comatose.
In addition, a consistent chronological link with the presumed 
underlying disease must be established.
Narcolepsy due to a medical condition is extremely rare.
(b) Idiopathic hypersomnia
In comparison with narcolepsy, which is characterized by well-deﬁ ned clinical, polysomnographic, and biochemical features, idio-
pathic hypersomnia is not as well delineated.
Its ﬁ rst description dates back to 1976,
(9) almost a century after

(9) almost a century after 
that of narcolepsy. According to various sleep disorders centres series populations the ratio of idiopathic hypersomnia to narco-lepsy with cataplexy would be around 15 per cent.
Idiopathic hypersomnia includes two forms referred to as idio-
pathic hypersomnia with long sleep time and idiopathic hyper-somnia without long sleep time. The ﬁ  rst one is remarkable for 
three symptoms: a complaint of constant or recurrent excessive sleepiness and unwanted naps, usually longer and less irresitible than in narcolepsy, and non-refreshing irrespective of their dura-tion; night sleep is sound, uninterrupted, and prolonged; morning or nap awakening is laborious. Subjects do not awaken to the ringing of a clock, of a telephone, and often rely on their family members who must use vigorous and repeated procedures to 
wake them up. Even then patients may remain confused, unable to

wake them up. Even then patients may remain confused, unable to 
react adequately to external stimuli, a state referred to as “sleep drunkenness” In contrast, idiopathic hypersomnia without long sleep time stands as isolated excessive daytime sleepiness.4.14.3 excessive sleepiness

SECTION 4  clinical syndromes of adult psychiatry 942
The diagnosis of idiopathic hypersomnia is mainly based on 
clinical features. However, laboratory tests are necessary to rule out other hypersomniac conditions. Polysomnographic moni-toring of nocturnal sleep demonstrates normal sleep, except for its prolonged duration in the case of idiopathic hypersomnia with long sleep time. NREM and REM sleep are in normalproportions. There is no SOREMP . Sleep apnoeas and periodic limb movements should theoretically be absent, but may be acceptable in the case of an early onset of idiopathic hypersom-nia and of their late occurrence. The MSLT usually demonstrates a mean sleep latency less than 8 min, but is typically longer than in narcolepsy. Fewer than two SOREMPs are present. In cases with normal MSLT ﬁ  ndings, several authors have suggested the 
use of long-term sleep monitoring to document the excessive amount of sleep.
In contrast with narcolepsy, onset of idiopathic hypersomnia is

In contrast with narcolepsy, onset of idiopathic hypersomnia is 
much more progressive. The disorder is generally stable and long lasting. Complications are mostly social and professional.
Treatment of idiopathic hypersomnia relies mainly on modaﬁ  nil. 
However, awakening difficulties are hardly improved by this treatment.
(c) Recurrent hypersomnia
The most classic form of recurrent hypersomnia is the Kleine–Levin syndrome.
(10) This is an uncommon disorder with roughly 
300 cases published in the world literature. Adolescent males are most commonly affected.
The syndrome is characterized by recurrent episodes of

hypersomnia associated with behavioural disorders includingbinge eating (rapid consumption of a large amount of food on a compulsory manner), oversexuality in the form of sexualadvances, shamlessly expressed fantasies or masturbation in public, irritability, odd behaviours (like standing on the head, singing loudly, talking in a childish manner), and cognitive disorders,feeling of unreality, confusion, visual or auditory hallucinations. Simultaneous occurrence of all these symptoms is more the excep-tion than the rule however. During the episode the patient may sleep as long as 14 to 18 h per day, waking or getting up only to eat and void.
Body weight gain of a few kilograms can be observed during the 
episode.
Amnesia of the episode, transient dysphoria, or elation with

episode.
Amnesia of the episode, transient dysphoria, or elation with 
insomnia for 1 or 2 days, may follow the episode itself. During asymptomatic intervals patients sleep normally and do not experi-ence behavioural or cognitive disorders.
Diagnosis of the Kleine–Levin syndrome is essentially clinical 
and laboratory tests merely serve to exclude the possibility of 
rare recurrent hypersomnias of secondary origin, organic, or psychiatric. Of note due to disordered behavioural features, espe-
cially hypersexuality, it is not rare that patients are ﬁ  rst hospitalized 
on psychiatric wards and given antipsychotic drugs.
The course is usually benign with episodes lessening in frequency, 
duration, and severity. Complications are mainly social and occupational.
Treatment of the Kleine–Levin syndrome is not well codiﬁ  ed. 
The effects of stimulant drugs such as modaﬁ  nil or methylpheni-

date on the hypersomniac episodes are difﬁ  cult to assess given that 
the methods of evaluation are purely subjective and that the episodes vanish spontaneously within a few days. A prophylactic treatment based on mood stabilizers (carbamazepine, lithium 
carbonate, and more recently valproic acid) deserves to be pre-scribed in severe cases. Positive results, that is absence of recurrence of the symptoms throughout the period of administration and recurrence with discontinuation, has been reported.
(d) Hypersomnias associated with various medical disorders
(i) Associated with neurological diseases

Hypersomnia may occur in any intracranial pressure syndrome, but it may also result from tumours affecting the diencephalon, specially the ventro-lateral posterior part of the hypothalamusor the peduncular region, with no associated intracranialhypertension. Cases of narcolepsy secondary to brain tumours affecting the hypothalamus or the midbrain region have been reported.
Uni or bilateral paramedian thalamic infarcts and paramedian 
pedunculo thalamic infarcts are the most typical causes of hyper-somnia of vascular origin.
A non-negligible fraction of patients with Parkinson’s disease 
present excessive sleepiness. This is even more the case of patients with multiple system atrophy.
Normal pressure hydrocephalus, Arnold–Chiari malformation, 
myotonic dystrophy, may also lead to excessive sleepiness.
(ii) Associated with infectious diseases

Intense fatigue and severe excessive sleepiness may develop in the 
month following Epstein–Barr disease. The same holds true of atypical viral pneumonia, hepatitis B viral infection and the Guillain–Barré syndrome. Hypersomnia tends to go into gradual remission after several months or years.
Disorders of alertness and/or consciousness are found in virtu-
ally all patients affected by viral encephalitis.
Human African Trypanosomiasis (sleeping sickness) is a sub-
acute or chronic parasitic disease caused by the inoculation of a protozoan, Trypanosoma brucei  transmitted by the tsetse ﬂ  y. It is 
endemic to certain regions of tropical Africa. The form foundin West and Central Africa is due to Trypanosoma gambiense . The

endemic to certain regions of tropical Africa. The form foundin West and Central Africa is due to Trypanosoma gambiense . The 
invasion of the central nervous system is characterized by meningo-encephalitis with abnormal sleepiness, headache, trembling,
dyskenesia, choreoathetosis, and mood changes. Polysomnography 
has shown episodes of sleep occurring randomly day and night and SOREMPs.
(iii) Associated with endocrine diseases
Hypothyroidism and acromegaly are the two main sources of hypersomnia, usually due to obstructive sleep apnoea syndrome.
(iv) Post-traumatic hypersomnia
Excessive daytime sleepiness appearing during the year following a head injury may be considered a priori  as post-traumatic. This 
typically presents as extended night sleep and episodes of daytime sleep. Brain imaging may reveal lesions affecting the hypothalamic region or brainstem, midbrain or pontine tegmentum, rarely hydrocephalia, or more often the absence of any significant lesions.

The delayed sleep phase syndrome
The major sleep episode is usually delayed 3 to 6 hours relative to conventional sleep-wake times. Affected individuals complain of great difﬁ  culty falling asleep at a socially acceptable time, but once 
sleep ensues, sleep is reported to be normal. Enforced conventional

943
wake time usually results in morning excessive sleepiness. The dis-
order has been associated with mental disorders, particularly in 
adolescents. Schizoid and avoidant personality features are fre-
quently associated with this disorder.
Treatment rests on various approaches including chronotherapy, 
light exposure, and melatonin therapy.
Hypersomnia deserves to be taken into consideration by the 
psychiatrist. It may be the consequence of a psychiatric disorder or of 
its treatment, but it may also be non psychiatric in nature and result 
in psychiatric symptoms.
Nofzinger, E.A., Thase, M.E., Reynolds, C.F., et al. (1991). Hypersomnia
in bipolar depression: a comparison with narcolepsy using the
multiple sleep latency test. The American Journal of Psychiatry ,148,
1177–81.
American Academy of Sleep Medicine. (1999). Sleep related breathing 
disorders in adults: recommendations for syndrome deﬁ  nition

1177–81.
and measurement techniques in clinical research. Sleep ,22,
667–89.
Dauvilliers, Y., Arnulf, I., and Mignot, E. (2007). Narcolepsy with cataplexy. 
Lancet ,369, 499–511.
Billiard, M. and Dauvilliers, Y. (2007). Idiopathic hypersomnia. In 
Narcolepsy and hypersomnia  (eds. C.L. Bassetti, M. Billiard, and 
E. Mignot), pp. 77–87. Informa Healthcare, New Y ork.
Arnulf, I., Zeitzer, J.M., File, J., et al. (2005). Kleine-Levin syndrome: a 
systematic review of 186 cases in the literature. Brain ,128,
2763–76.
Regenstein, Q. and Monk, T. (1995). Delayed sleep phase syndrome:
a review of its clinical aspects. The American Journal of Psychiatry ,152,
602–8.
 1. American Academy of Sleep Medicine. (2005). International 
classiﬁ  cation of sleep disorders: diagnostic and coding manual  (2nd edn).

602–8.
 2. Ohayon, M.M., Caulet, M., Philip, P ., et al. (1997). How sleep and 
mental disorders are related to complaints of daytime sleepiness. 
Archives of Internal Medicine ,157, 2645–52.
 3. Liu, X., Uchiyama, M., Kim, K., et al. (2000). Sleep loss and daytime 
sleepiness in the general adult population of Japan. Psychiatric Research ,
93, 1–11.
 4. Guilleminault, C., Tilkian, A., and Dement, W.C. (1976). The sleep 
apnea syndromes. Annual Review of Medicine ,27, 465–84.
 5. Y oung, T., Palta, M., Dempsey, J., et al. (1993). The occurrence of sleep 
disordered breathing among middle-aged adults. The New England 
Journal of Medicine ,328, 1230–5.
 6. Ohayon, M.M. (2003). The effects of breathing-related sleep disorders

 6. Ohayon, M.M. (2003). The effects of breathing-related sleep disorders 
on mood disturbances in the general population. Journal of Clinical 
Psychiatry ,64, 1195–2000.
 7. Westphal, C. (1877). Eigentümliche mit Einschlafen verbundene 
Anfälle. Archives für Psychiatrie und Nervenkrankheiten ,
7, 631–5.
 8. Gelineau, J. (1880). De la narcolepsie. Gazette des Hôpitaux  (Paris), 55,
626–8; 635–7.
 9. Roth, B. (1976). Narcolepsy and hypersomnia. Schweizer Archiv für 
Neurologie und Psychiatrie ,119, 31–41.
10. Critchley, M. (1962). Periodic hypersomnia and megaphagia in 
adolescent males. Brain ,85, 627–56.4.14.4 Parasomnias
Carlos H. Schenck, and Mark W. Mahowald
In all of us, even in good men, there is a lawless, wild-beast nature 
which peers out in sleep. –Plato, The Republic
Relevance of parasomnias to psychiatrists
Parasomnias are deﬁ  ned as undesirable physical and/or experien-

tial phenomena accompanying sleep that involve skeletal muscle 
activity (movements, behaviours), autonomic nervous system 
changes, and/or emotional-perceptual events.(1) Parasomnias can 
emerge during entry into sleep, within sleep, or during arousals 
from any stage of sleep; therefore, all of sleep carries a vulnerability 
for parasomnias.(1) Parasomnias can be objectively diagnosed by 
means of polysomnography (i.e. the physiologic monitoring of 
sleep—ﬁ  gures 4.14.4.1, 4.14.4.2), and can be successfully treated in 
the majority of cases.(2–5) Understanding of the parasomnias, based 
on polysomnographic documentation, has expanded greatly over 
the past two decades, as new disorders have been identiﬁ  ed, and as 
known disorders have been recognized to occur more frequently,

known disorders have been recognized to occur more frequently, 
across a broader age group, and with more serious consequences 
than previously understood.(1–10) Parasomnias demonstrate how 
our instinctual behaviours, such as locomotion, feeding, sex, and 
aggression, can be released during sleep, itself a basic instinct. There 
are at least eight reasons why parasomnias should be of interest and 
importance to psychiatrists:
Fig. 4.14.4.1 Polysomnogram of a disordered arousal, with the persistence of 
sleep, in a 23-year-old man with a history of sleepwalking and sleep terrors. After a 
behavioural arousal from slow-wave sleep (with arm lifted up and then down), the 
EEG shows irregular delta and theta activity and superimposed faster frequencies. 
Immediately preceding the arousal, there is a cluster of three high-amplitude delta

Immediately preceding the arousal, there is a cluster of three high-amplitude delta 
waves (channel 3). Electro-occulogram, channels 1. 2; EEG, channels 3, 10–17; EMG, 
electromyogram. (Reproduced from C.H. Schenck et al. Analysis of polysomnographic 
events surrounding 252 slow-wave sleep arousals in thirty-eight adults with injurious 
sleepwalking and sleep terrors.  Journal of Clinical Neurophysiology , 15, 159–66, 
copyright 1998, American Clinical Neurophysiology Society)
4.14.4 parasomnias

SECTION 4  clinical syndromes of adult psychiatry 944
1 Parasomnias can be misdiagnosed and inappropriately treated 
as a psychiatric disorder.
2 Parasomnias can be a direct manifestation of a psychiatric 
disorder, e.g. dissociative disorder, nocturnal bulimia nervosa.
3 The emergence and/or recurrence of a parasomnia can be 
triggered by stress.
4 Psychotropic medications can induce the initial emergence of 
a parasomnia, or aggravate a preexisting parasomnia.
5 Parasomnias can cause psychological distress or can induce or 
reactivate a psychiatric disorder in the patient or bed partner 
on account of repeated loss of self-control during sleep and 
sleep-related injuries.
6 Familiarity with the parasomnias will allow psychiatrists
to be more fully aware of the various medical and neuro-
logical disorders, and their therapies, that can be associated 
with disturbed (sleep-related) behaviour and disturbed
dreaming.
7 Parasomnias present a special opportunity for interlinking

dreaming.
7 Parasomnias present a special opportunity for interlinking 
animal basic science research (including parasomnia animal 
models) with human (sleep) behavioural disorders.
8 Parasomnias carry forensic implications, as exempliﬁ  ed by the 
newly-recognized entity of ‘Parasomnia Pseudo-suicide.’ Also, 
psychiatrists are often asked to render an expert opinion in 
medicolegal cases pertaining to sleep-related violence.Classiﬁ  cation of parasomnias
Parasomnias can be classiﬁ  ed according to whether the signs 
or symptoms are primary phenomena of sleep itself, or whether 
they are secondary phenomena derived from various underlying 
disorders, with sleep facilitating the nocturnal manifestation of 
these disorders.(6) Table 4.14.4.1 contains such a classiﬁ  cation, and 
provides a context (along with other current sources(1,11)) for the

provides a context (along with other current sources(1,11)) for the 
parasomnias to be discussed in this chapter. Parasomnias demon-
strate how sleep and wakefulness are not mutually exclusive states. 
Features of rapid eye movement (REM) sleep, non-REM sleep and 
wakefulness can occur simultaneously, and with rapid oscillations.(12)
Status dissociatus represents the most extreme form of state 
dissociation.(13)
Clinical evaluation of parasomnias
The evaluation of complex and violent nocturnal behaviours at our 
centre (Minnesota Regional Sleep Disorders Center) includes the 
following:(2,14)
1 Clinical sleep-wake interview, with review of medical records, 
and review of a patient questionnaire that covers sleep-wake, 
medical, psychiatric and alcohol/chemical use and abuse history, 
review of systems, family history, and past or current physical, 
sexual, and emotional abuse.

2 Psychiatric and neurologic interviews and examinations, includ-
ing psychometric testing.
Table 4.14.4.1  Classiﬁ  cation of parasomnias: primary and 
secondary sleep phenomena
Primary sleep phenomena
Non-REM sleep
 Disorders of arousal: sleepwalking/sleep terrors/confusional arousal
REM sleep
 REM sleep behaviour disorder (RBD)
 Dream anxiety attacks (nightmares)
Miscellaneous (including mixed non-REM/REM sleep)
 Parasomnia overlap disorder (sleepwalking/sleep terrors/RBD)
 Sleep related eating disorder
 Restless legs syndrome/periodic limb movements in sleep
 Obstructive sleep apnoea-related parasomnias
 Rhythmic movement disorders
 Status dissociatus
 Bruxism
Secondary sleep phenomena
Central nervous system
 Seizures (conventional, unconventional)
 Headaches
Psychiatric
 Nocturnal dissociative disorders

Status dissociatus
 Bruxism
 Headaches
 Nocturnal panic attacks
 Nocturnal bulimia nervosa
 Post-traumatic stress disorder
Cardiopulmonary (arrhythmias, asthma, etc.)
Gastrointestinal (gastro-oesophageal reﬂ  ux etc)
Modiﬁ  ed from Mahowald and Ettinger.(7)Fig. 4.14.4.2 Polysomnogram of disordered rapid eye movement (REM) sleep in 
a man with REM sleep behaviour disorder who eventually developed Parkinson’s 
disease. There is complete loss of ‘REM-atonia’, as the submental electromyogram 
(EMG) shows continuous muscle tone (channel 7). The appearance of a rapid 
eye movement (channels 1, 2) signals the onset of excessive muscle twitching in 
the upper/lower extremity EMGs (channels 8–15). The EEG (channels 3–6) shows 
the typical low-voltage fast-frequency desynchronized activity of REM sleep.

the typical low-voltage fast-frequency desynchronized activity of REM sleep. 
ECG rate (channel 16) remains constant despite generalized muscle twitching, 
which is a common ﬁ  nding in REM sleep behaviour disorder. Elecro-oculogram: 
channels 1,2.

945
3 Extensive overnight polysomnographic monitoring at a hospital 
sleep laboratory, with continuous audio-visual recording. Figures 4.14.4.1, 4.14.4.2 depict the polysomnographic montage that includes the electro-oculogram, EEG, chin and four-limb electromyograms, ECG, and nasal-oral airﬂ  ow (with full respira-
tory monitoring whenever indicated). Polysomnographic record-ing speeds of 15 to 30 mm/s are employed in order to detect epileptiform activity. Urine toxicology screening is performed whenever indicated.
4 Daytime multiple sleep latency testing, if there is a complaint or 
suspicion of excessive daytime sleepiness or fatigue (methods discussed in Narcolepsy chapter).
Causes of sleep related injury
A report on a series of 100 consecutive adults presenting to a multi-disciplinary sleep disorders centre on account of sleep-related injury identiﬁ  ed ﬁ  ve causes:
(2)
1 Sleepwalking/sleep terrors (M:F 3:2; mean age of onset, 5 years);

(2)
2 REM sleep behaviour disorder (predominantly male; mean age 
of onset, 57 years)
3 Dissociative disorders (Mostly female mean age of onset, 
21 years)
4 Nocturnal seizures (uncommon)
5 Obstructive sleep apnoea/periodic limb movements (uncommon).
The sleep-related injuries included ecchymoses, lacerations, and 
fractures in 95 per cent, 30 per cent, and 9 per cent of patients 
Non-REM sleep parasomnias: sleepwalking 
and sleep terrors
The polysomnographic correlates of sleepwalking and sleep terrors 
were first identified in the 1960s and 1970s by Gastaut and Broughton,
(15, 16) Kales et al.,(17) and Fisher et al.(18) from France, 
Canada, and the United States. Sleepwalking and sleep terrors are classiﬁ  ed as ‘disorders of arousal,’ and typically arise from delta 
non-REM (slow wave) sleep and usually affect children, but adults can also be afﬂ  icted, and suffer from sleep-related injuries and

non-REM (slow wave) sleep and usually affect children, but adults can also be afﬂ  icted, and suffer from sleep-related injuries and 
adverse social consequences.
(2,9,10,19–24)
Clinical ﬁ  ndings
Sleepwalking (SW) is characterized by complex, automatic behav-
iours, such as aimlessly wandering about, nonsensically carrying objects from one place to another, rearranging furniture, eating inappropriately, urinating in cupboards, going outdoors, and on rare occasion, driving a car.
(1,25,26)  The eyes are usually wide open 
and have a glassy stare, and there may be some mumbling. However, communication with a sleepwalker is usually poor or impossible. Frenzied or aggressive behaviour, the wielding of weapons (knives, guns), or the calm suspension of judgement (e.g. leaving via a bed-room window, wandering far outdoors) can result in inadvertent 
injury or death to self or others. Homicidal sleepwalking can 
occur.
(25)
Sleepwalking episodes usually emerge 15–120 minutes after sleep

occur.
(25)
Sleepwalking episodes usually emerge 15–120 minutes after sleep 
onset, but can occur throughout the entire sleep period in adults. The duration of each episode can vary widely. The following 
is a wife’s description.(2)
‘He seems to have the strength of 10 men and shoots straight 
up from bed onto his feet in one motion. He’s landed clear across the room on many occasions and has pulled down curtains (bending the rods), upset lamps, and so forth. He’s grabbed me and pulled on me, hurting my arms, because he’s usually dreaming that he’s getting me out of danger . . . He’s landed on the ﬂ  oor so 
hard that he’s injured his own body . . . There are low windows right beside our bed and I’m afraid he’ll go through them some night.’
Sleep terrors (ST) are characterized by sudden, loud, terriﬁ  ed

Sleep terrors (ST) are characterized by sudden, loud, terriﬁ  ed 
screaming and prominent autonomic nervous system activation (tachycardia, tachypnea, diaphoresis, mydriasis) that usually appears early in the sleep period, although episodes in adults can occur at any time of the night. The individual may sit up rapidly while screaming, and engage in frenzied activity, such as bolting out of bed, and becoming injured.
Childhood sleepwalking and sleep terrors are characterized 
by complete amnesia for the events. In adult SW and ST, there can be subsequent recall of the behavioural episode, and also recall of dream-like mentation that usually involves being threatened by imminent danger.
(2,27) The distinction between ST and agitated 
SW in adults is often blurred, with both states being admixed in response to a perceived threat.
(24)
The prevalence of SW has been estimated to be as high as

(24)
The prevalence of SW has been estimated to be as high as 
17 per cent in childhood (peaking at age 4–8), and recent data indicate a higher prevalence in adults (4 per cent) than previously recognized.
(28–30)  The prevalence of ST in children can be greater 
than 6 per cent and greater than 2 per cent in adults.(1) A familial-
genetic basis for SW and ST has been well-established.(30,31)
Non-injurious SW does not have a gender preference,(1) although 
injurious SW appears to be more male-predominant.(2) Sleep 
terrors do not have a gender preference.(1) ‘Confusional arousals’ 
comprise another category of ‘disorder of arousal,’ and represent partial manifestations of sleepwalking and sleep terrors in which aggression and sexual impulses can be released.
(1,10)
Polysomnographic ﬁ  ndings
Sleepwalking/sleep terrors episodes arise abruptly during arousals

(1,10)
Sleepwalking/sleep terrors episodes arise abruptly during arousals 
from delta non-REM sleep.(1,15–18) In a systematic study of 
38 adults with injurious SW/ST,(24) three postarousal EEG 
patterns were detected: diffuse, rhythmic delta activity; diffuse delta and theta activity intermixed with alpha and beta activity; and prominent alpha and beta activity. Thus, the postarousal EEG can show the complete persistence of sleep, the admixture of sleep and wakefulness, or complete wakefulness. Figure 4.14.4.1 shows the polysomnogram of a disordered arousal from slow-wave sleep.
Although the sleep architecture (i.e. distribution of sleep stages) 
is usually normal in SW and ST, the ‘micro-structure’ of non-REM sleep in adult SW/ST can be perturbed, with increased micro-arousals and increased rate of the ‘cyclic alternating EEG pattern’ .
(1,2, 21,23)
Association with medical and psychiatric risk factors

Sleepwalking and sleep terrors may be triggered by sleep depriva-tion, febrile illness, alcohol use or abuse, pregnancy, menstruation, obstructive sleep apnea, periodic limb movements, nocturnal 4.14.4 parasomnias

SECTION 4  clinical syndromes of adult psychiatry 946
seizures, medical and neurological disorders, and psychotropic 
medications—especially zolpidem, lithium carbonate and anti-cholinergic agents.
(1)
A strong association between sleepwalking/sleep terrors and 
psychopathology in adults was suggested by an early literature, but polysomnograpic monitoring was not conducted, and there were considerable methodological problems. The recent literature reporting PSG-conﬁ  rmed cases has indicated that most adult 
cases are not closely associated with a psychiatric disorder, although stress can play a promoting role
(2,19,29,22,32) . Genetic-constitutional 
factors appear to be predominant in adult and childhood sleep-walking/sleep terrors.
(1)
Treatment
Treatment (especially in childhood SW/ST) is usually not neces-sary, other than identifying and minimizing any identiﬁ  ed risk

(1)
Treatment
Treatment (especially in childhood SW/ST) is usually not neces-sary, other than identifying and minimizing any identiﬁ  ed risk 
factors, and safety measure to avoid accidental injury. In cases involving sleep-related injury, pharmacological treatment is neces-sary and can be life-saving. A benzodiazepine, such as clonazepam (0.25–1.5 mg) taken 1 hour before sleep onset is usually effective. Alprazolam, diazepam, imipramine, and paroxetine can also be used. T eaching a patient self-hypnosis can be effective in milder cases of either adult or childhood SW/ST.
(33) Treatment of any con-
current psychiatric disorder does not usually control sleepwalking/sleep terrors.
(2,22) Attempts to waken the patient may cause confu-
sion and distress.
REM sleep behaviour disorder (RBD)
Although various aspects of RBD have been identiﬁ  ed by European, 
Japanese and American investigators since 1966,(34) RBD was not for-

mally recognized and named until 1986–1987,(35,36) and it is incorpo-
rated within the international classiﬁ  cation of sleep disorders.(1)
A typical clinical presentation of RBD is contained in the description 
of the index case:(35)
‘A 67-year-old dextral man was referred because of violent behavior during sleep . . . 4 years before referral . . . he experienced the ﬁ  rst

‘A 67-year-old dextral man was referred because of violent behavior during sleep . . . 4 years before referral . . . he experienced the ﬁ  rst 
‘physically moving dream’ several hours after sleep onset; he found himself out of bed attempting to carry out a dream. This episode signaled the onset of an increasingly frequent and progressively severe sleep disorder; he would punch and kick his wife, fall out of bed, stagger about the room, crash into objects, and injure himself . . . his wife began to sleep in another room 2 years before referral. They remain happily married, believing that these nocturnal behaviors are out of his control and discordant with his waking personality.’
Mammalian REM sleep, REM atonia, and paradox lost
REM sleep in mammals involves a highly energized state of brain activity, with both tonic (i.e. continuous) and phasic (i.e. intermit-tent) activations occurring across a spectrum of physiologic parameters.

(36) REM sleep has two major synonyms: ‘active sleep,’ 
because of the high level of brain activity during REM sleep, and ‘paradoxical sleep,’ because of the nearly complete suppression of muscle tone despite the high level of brain activity. This generalized skeletal muscle atonia (‘REM-atonia’) is one of the three deﬁ  ning 
features of mammalian REM sleep, besides rapid eye movements and a desynchronized EEG. The loss of the customary paradox of REM sleep in RBD bears serious clinical consequences: ‘paradox lost’ means loss of safe sleep.
(9)Animal model of RBD
In 1965, Jouvet and Delorme reported from France that experi-mental pontine lesions in cats caused permanent loss of REM-ato nia, and the cats displayed attack and exploratory
behaviours during REM sleep that resembled dream-enactment (oneirism). This experiment established the ﬁ  rst animal model
of RBD.
(34)
Clinical and polysomnographic ﬁ  ndings
Between 1982 and 1991, 96 patients at our centre were diagnosed

of RBD.
(34)
Between 1982 and 1991, 96 patients at our centre were diagnosed 
with chronic RBD. (There is an acute form of RBD that can emerge during withdrawal from ethanol or sedative-hypnotic abuse and with anti-cholinergic and other drug intoxication states.
(36) Data on this series(37) are contained in Table 2, and
are concordant with the published world literature.(34,36) The 
older male predominance in RBD is striking, although females and virtually all age groups are represented. Approximatelyhalf of RBD cases are closely associated with neurological disor-ders, predominantly neurodegenerative disorders (especiallyparkinsonism), narcolepsy and stroke. In fact, RBD may be the first sign of a parkinsonian disorder whose other (classic)manifestations may not emerge until several years or even decades after the onset of RBD.
(36,38,39) Thus, routine neurological

evaluations are indicated in the long-term management of RBD. The prevalence of RBD is estimated to be from 0.38 per cent to 0.5 per cent.
(1) The course is usually progressive; spontaneous 
Table 4.14.4.2 Findings in 96 patients with chronic REM sleep 
behaviour disorder (RBD)
Categories Percentage (N) Comments
Gender
Male 87.5 (84) Mean age of RBD onset ( N = 90):
Female 12.5 (12) 52 years (range 9–81)
Mean age at polysomnography:58 years (range 10–83)
Chief complaint
Sleep injury 79.2 (76) Ecchymoses (76); lacerations (32); 
fractures (7)
Sleep disruption 20.8 (20)Altered dream process 
and content87.5 (84) More vivid, intense, action ﬁ  lled, 
violent (reported as severe 
nightmares)
Dream-enacting 
behaviours87.5 (84) Talking, laughing, yelling, swearing, 
gesturing, reaching, grabbing, arm 
ﬂ  ailing, punching, kicking, sitting, 
jumping out of bed, crawling, running
Clonazepam treatment
Efﬁ  cacy ( N = 67)

Complete 79.1 (44/67) Rapid control of problematicPartial 11.9 (8/67) sleep behaviours and
Total 91.0 (61/67) altered dreams, sustained for up 
to 9 years
Modiﬁ  ed from Schenck et al.(36)

947
remissions are very rare. Patients with RBD usually have calm and 
pleasant personalities, and do not display irritability or anger while awake, even though their dreams are highly aggressive.
(40)
Figure 4.14.4.2 depicts a typical polysomnogram of RBD with attempted dream-enactment.
Association of RBD with psychiatric disorders 
and Stress
Psychiatric disorders are rarely associated with RBD.(34,41)
Fluoxetine treatment of obsessive compulsive disorder,(42) or 
cessation of use or abuse of REM-suppressing agents (viz. ethanol, amphetamine, cocaine, imipramine) can trigger RBD.
(36,43)
Tricyclic antidepressants, selective serotonin reuptake inhibitors, venlafaxine, mirtazapine, and monoamine oxidase inhibitors can induce or aggravate RBD. In four cases, major stress involving divorce, automobile accident, sea disaster, or public humiliation triggered RBD.
(2,34,43)
Diagnosis of RBD
The diagnostic criteria of RBD are as follows:(1,36)

(2,34,43)
1 Polysomnographic abnormality during REM sleep: elevated 
submental electromyographic tone and/or excessive phasic submental and/or limb electromyographic twitching.
2 Documentation of abnormal REM sleep behaviours during 
polysomnographic studies, or a history of injurious or disruptive sleep behaviours.
3 Absence of EEG epileptiform activity during REM sleep.
Treatment of RBD
Clonazepam is remarkably effective in controlling both the behav-
ioural and the dream-disordered components of RBD, at a usual bedtime dose of 0.5 to 1.0 mg. The long-term efﬁ  cacy and safety 
of chronic, nightly clonazepam treatment of RBD has been established.
(3) Other treatments include melatonin, pramipexole, 
etc.(36) Maximizing the safety of the sleeping environment should 
always be encouraged.
Parasomnia overlap disorder: sleepwalking/
sleep terrors/RBD
A group of 33 patients has been reported with polysomnogram-

documented sleepwalking, sleep terrors, and RBD.(8) The mean age 
was 34 years, the mean age of parasomnia onset was 15 years (range: 1–66), and 70 per cent were male. An idiopathic subgroup (N =22)
had a signiﬁ  cantly earlier mean age of parasomnia onset (9 years) 
than a symptomatic subgroup (27) whose parasomnia beganwith either a neurologic disorder (N =6), nocturnal paroxysmal 
atrial fibrillation (N =1), post-traumatic stress disorder/
major depression (N =1), chronic ethanol/amphetamine abuse
and withdrawal (N =1), or mixed disorders (schizophrenia; brain 
trauma; substance abuse [N =2]). The rate of psychiatric disorders 
was not elevated; group scores on various psychometric tests were not elevated. Forty-ﬁ  ve percent (N =15) had previously received

was not elevated; group scores on various psychometric tests were not elevated. Forty-ﬁ  ve percent (N =15) had previously received 
psychologic or psychiatric therapy for their parasomnia, without beneﬁ  t. Treatment, usually with clonazepam, was effective for
most patients. The natural history of this disorder is not yet
known. Other cases of Parasomnia Overlap Disorder have been
reported.
(34,36)Sleep related eating disorder
The ‘night-eating syndrome’ was first reported in 1955, and featured abnormal eating during full wakefulness in insomniac patients. Over the next 35 years, abnormal nocturnal eating received scant attention in the literature, until a series of 19 cases (expanded to 38 cases) with polysomnographic data was published on the new entity of sleep related eating disorder,
(1,4,44) which featured abnor-
mal eating during partial arousals from sleep in patients with other parasomnias or those who were idiopathic. Reports from various countries have now been published.

(45–49)
Pathological sleep-related eating has characteristic features, as 
identiﬁ  ed in two separate series of adult cases.(4,44,48) Neither

(45–49)
identiﬁ  ed in two separate series of adult cases.(4,44,48) Neither 
daytime binge-eating nor obsessive-compulsive disorder was diagnosed in any patient. Sleep-related eating was not associated with either the onset or the course of a psychiatric disorder. Patients do not usually experience hunger or thirst during their ‘driven’ nocturnal eating and drinking. A typical behavioural sequence consists of ‘automatic’ arising from bed, and going straight to the kitchen with a compulsive ‘out of control’ urge to eat. Alcohol is almost never consumed, even in former alcohol abusers. Thick substances, such as milkshakes, peanut butter, and brownies, are preferentially consumed at night. Purging does not take place, either at night or in the morning. Sleep-related eating is usually invariant, and is not inﬂ  uenced by day of the week or sleeping away

from home. More than 40 per cent of patients in one series were overweight from the nocturnal eating, according to standardized 
body mass index criteria.
(4)
Sleep related eating is most commonly associated with sleepwalk-
ing, but also with restless legs syndrome, obstructive sleep apnoea, narcolepsy, zolpidem/triazolam/midazolam/other psychotropic medication use or abuse, cessation of cigarette smoking, cessation of alcohol, opiate and cocaine abuse; cessation of cigarette smoking; stress (particularly involving separation anxiety), and vari-ous medical/neurological disorders (e.g. autoimmune hepatitis, encephalitis, migraines). Rarely, anorexia or bulimia nervosa or a dis-sociative disorder can be associated with sleep-related eating.
(45)
Prescribing a monoamine oxidase inhibitor to a patient with 
sleep related eating disorder can be hazardous, since indiscriminate food consumption at night could jeopardize the mandatory dietary restrictions of MAOI treatment.
Treatment

Treatment
Treatment, with one notable exception, is primarily directed at controlling the underlying sleep disorder. For cases associated with restless legs syndrome, therapy with dopaminergics (at times supplemented with an opiate such as codeine) is usually effective; likewise, therapy of obstructive sleep apnoea with nasal continuous positive airway pressure is often effective in controlling the sleep related eating. In contrast, in cases that are idiopathic and in those cases associated with sleepwalking, therapy with the anticonvulsant topiramate (that suppresses overeating urges) was effective in two-thirds of cases in two reported series.
(5,50)
Sleep related eating disorder shares many features in common 
with the ‘night eating syndrome’ in adults,(49,51)  although there

(5,50)
with the ‘night eating syndrome’ in adults,(49,51)  although there 
are usually major differences in regards to level of consciousness during nocturnal eating, association with other sleep disorders, 4.14.4 parasomnias

SECTION 4  clinical syndromes of adult psychiatry 948
and response to therapy. It is likely that these two conditions sit at 
opposite poles of a spectrum of abnormal nocturnal eating.
Sleep related dissociative disorders
A nocturnal dissociative disorder with polysomnographic monitoring was ﬁ  rst reported in 1976 by Rice and Fisher in a man 
with daytime and night-time fugues that began after his father’s death.
(52) Another polysomnogram-documented case was 
described in a woman with a history of being physically and sexually assaulted.
(1) A series of eight cases was reported from our 
centre in 1989.(53)
Clinical manifestations
The onset may be sudden or gradual, and the course is chronic. There usually is a history of repeated physical and sexual abuse in childhood and/or adulthood. In a series of eight cases, seven were female who also had daytime states of dissociation with self-mutilating behaviours, such as genital cutting, self-burning, and punching through windows.

(53) One male patient had exclusively 
nocturnal episodes in which he acted like a jungle cat. Patients may report sleep phobia as a consequence of bed-related and sleep-related sexual and physical abuse.
A typical spell during polysomnographic monitoring involves 
complex and lengthy behaviours that emerge during well-established EEG wakefulness, after a prior episode of sleep.
(53) The nocturnal 
episodes appear to be re-enactments of previous assaults.
Treatment
Treatment involves long-term therapy of the dissociative disorders and of associated psychiatric disorders, usually initiated in a specialized in-patient setting. Bedtime administration of benzodi-azepines may aggravate a nocturnal dissociative disorder.
Restless legs syndrome (RLS)
RLS, ﬁ  rst described in 1945 by Ekbom from Sweden, is a chronic 
disorder that often results in severe insomnia, and can be incapaci-tating.
(1,54)  It is characterized by unpleasant and at times painful

(1,54)  It is characterized by unpleasant and at times painful 
sensations in the lower extremities that emerge during periods of inactivity, particularly during the transition from wakefulness to sleep. These abnormal sensations are relieved by movement or stimulation of the legs, such as walking, stomping the feet, rubbing or squeezing the legs, taking hot showers, or applying hot packs or ointments to the legs.
Both the RLS and the therapeutic interventions just described 
are incompatible with successful entry into sleep. The more severely affected individuals cannot easily sit still while watching television or a ﬁ  lm, or during protracted plane or train journeys. RLS is quite 
common, affecting up to 10 per cent of the general population, and tends to become more prevalent with increasing age. It affects females more than males. Childhood cases, though rare, at times

common, affecting up to 10 per cent of the general population, and tends to become more prevalent with increasing age. It affects females more than males. Childhood cases, though rare, at times 
may masquerade as ‘attention deﬁ  cit disorder with hyperactivity,’ 
or as ‘growing pains.’
Most RLS cases are idiopathic with a strong familial basis. 
Caffeine, fatigue, or stress may worsen the symptoms. There is no evidence that RLS is related to psychiatric disorders, although the symptoms of RLS may suggest a primary anxiety disorder and through impairment of the duration and quality of sleep it can affect daytime mood and behaviour. Also, neuroleptic-induced akathisia can mimic RLS. Secondary RLS can be associated 
with peripheral neuropathies, renal disease, and psychotropic 
medications (especially the SSRIs, venlafaxine, and tricyclic 
antidepressants).
Nearly all patients with RLS have ‘periodic limb movements’

Nearly all patients with RLS have ‘periodic limb movements’ 
(PLMs) of non-REM sleep (formerly called ‘nocturnal myoclonus’). PLMs are characterized by periodic (every 15–40 sec) movements of the legs, viz. slow dorsi-ﬂ  exion, which may or may not be associated 
with arousals. Excessive arousals during sleep from any cause, including PLMs, may result in daytime fatigue or sleepiness.
RLS can usually be diagnosed by history alone, and polysomno-
graphic monitoring is usually not indicated. The syndrome is one of the major organic causes of insomnia, and commonly responds to treatment that includes use of dopaminergics (e.g. pramipexole, ropinerole, levodopa), opiates, and benzodiazepines (e.g. clonaze-pam). Combinations of these drugs are often necessary. Since RLS is a chronic disorder that often worsens with advancing age, chron-ic long-term treatment is usually warranted.

Differential diagnosis of dream-enacting 
behaviours and other parasomnias
A history of dream-enacting behaviours does not automatically 
implicate RBD. Other diagnoses include sleepwalking/sleep terrors;
(2,9) obstructive sleep apnoea, with apnoea-induced arous-
als from REM sleep being associated with violent behaviours and vivid REM-related dreams;
(2,55)  nocturnal complex seizures, with 
the ‘dreams’ being the seizure equivalents;(34) sleep related dissocia-
tive disorders, with the ‘dreams’ being wakeful memories of past abuse;
(53) intoxication states; and malingering.
Other parasomnias of interest to psychiatrists include sexual 
parasomnias (‘sleepsex’ , ‘sexsomnia’),(10) nocturnal panic attacks, 
which arise from Stages II and III non-REM sleep,(56) sleep related 
trichotillomania, nocturnal frontal lobe epilepsy,(11) and rhythmic

trichotillomania, nocturnal frontal lobe epilepsy,(11) and rhythmic 
movement disorders of non-REM and REM sleep, including head-banging and body rocking. Finally, expanded knowledge on the parasomnias has allowed for the recognition of a new medical-legal entity called ‘parasomnia pseudo-suicide’ .
(58) This 
term refers to the unfortunate, but unintentional, fatal consequence of complex, sleep-related behaviours that may be erroneously attributed to suicide.
(1)
Forensic guidelines for psychiatrists
The legal implications of automatic behaviour have long been discussed and debated. With regard to sleep-related automatic behaviours, the objective identiﬁ  cation of a sleep disorder does 
not establish causality for any given deed. Guidelines have been developed to assist in determining the role of a sleep disorder in an act of violence.
(57)
X There should be reason (by history or by formal sleep labora-

(57)
tory evaluation) to suspect a bona ﬁ  de sleep disorder. Similar 
episodes, with benign or morbid outcome, should have occurred previously. (Note that disorders of arousal may begin in adulthood).
X The duration of the action is usually brief (minutes).
X The behaviour is usually abrupt, immediate, impulsive, and 
senseless—without apparent motivation. Although ostensibly

949
purposeful, it is completely inappropriate to the total situa-
tion, out of (waking) character for the individual, and without evidence of premeditation.
X The victim is someone who merely happened to be present 
and who may have been the stimulus for the arousal.
X Immediately after return to consciousness, there is perplexity 
or horror, without an attempt to escape, conceal, or cover up the action. There is evidence of lack of awareness on the part of the individual during the event.
X There is usually some degree of amnesia for the event, however, 
this amnesia may not be complete.
X In the case of ST or SW or sleep drunkenness, the act may 
(a) occur on awakening, (rarely immediately upon falling asleep) and usually at least 1 hour after sleep onset; (b) occur on attempts to awaken the subject; and (c) have been potenti-ated by alcohol ingestion, sedative or hypnotic administration or prior sleep deprivation.
The American Academy of Neurology and other professional

The American Academy of Neurology and other professional 
organizations have developed guidelines for expert witnesses, with the most stringent being as follows.
XThe expert should be willing to submit his or her testimony for peer review.
XThe expert must be impartial and be willing to prepare his or her testimony for use by either or both the plaintiff or defendant. Ideally, the expert should assume the role of ‘friend of the court.’
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4.15
Suicide
4.15.1 Epidemiology and 
causes of suicide
Deﬁ nition of suicide and the reliability of 
suicide statistics
Suicidal behaviour or suicidality can be conceptualized as a 
continuum ranging from suicidal ideation and communications to suicide attempts and completed suicide. A developmental process which leads to suicidal ideation, suicidal communication, self-destructive behaviour, in some cases even to suicide, and its consequences to the survivors is often referred to as a suicidal process. There is no single unanimously accepted deﬁ  nition of 
suicide, although in most proposed deﬁ  nitions it is considered as

suicide, although in most proposed deﬁ  nitions it is considered as 
a fatal act of self-injury (self-harm) undertaken with more or less conscious self-destructive intent, however vague and ambiguous. Since the deceased cannot testify as to his or her intent, the conclu-sions about this must be drawn by inference. The evidence required for this inference depends on many factors, for example the mode of death, the use of autopsy, age, gender, social and occupa-tional status, and the social stigma of suicide in the person’s culture. The assessment of suicide intent is always based on a bal-
ance of probabilities.
Besides the conceptual problems, there are differences in opera-
tional deﬁ  nitions of suicidal behaviour which may lead to lack of 
uniformity of case deﬁ  nition and difﬁ  culties in comparing suicide 
statistics. The reliability of suicide statistics is inﬂ  uenced by whether 
suicide is ascertained by legal ofﬁ  cials as in the United Kingdom

suicide is ascertained by legal ofﬁ  cials as in the United Kingdom 
and Ireland, or by medical examiners as elsewhere in Europe. In general, suicides tend to be undercounted, whereas non-suicidal deaths are very rarely misidentiﬁ  ed as suicides. Most misclassiﬁ  ed 
suicides fall into the category of undetermined deaths and are more like suicides than accidents. Underestimation is reasoned to be less than 10 per cent in the more developed countries, which allows rate comparisons between countries and over time. Despite problems in the recording of suicide, reports on suicide rates among different cultures or people suggest a true variation in suicide mortality.
(1,2)
The suicide process and the act of suicide

(1,2)
Suicide is a mode of death usually consequent to a complex and multifaceted behaviour pattern. It is typically seen as the fatal outcome of a long-term process shaped by a number of interacting cultural, social, situational, psychological, and biological factors. Suicide is a rare, shocking, and very individual ﬁ  nal act, which 
often leaves the survivors helpless. The suicide process model is used to organize and clarify the complexity of factors associated with suicide (Fig. 4.15.1.1).
Suicide is usually preceded by years of suicidal behaviour or 
feelings, and plans and warnings. In about half of all suicides, a previous attempt is found in the person’s history, which offers, in theory, an opportunity for suicide intervention wherever suicide attempts occur. Male suicide attempts are more violent and the ﬁ  rst 
attempt more likely to end in death. Successful suicide prevention

attempt more likely to end in death. Successful suicide prevention 
calls for sensitive understanding of suicidal intent and active early 
intervention.
(3)
Various risk or protective factors underlie suicidal behaviour. 
An appearance of suicidality means either an intensiﬁ  ed effect of 
risk factors or a weakened effect of protective factors. For example, a separation from someone close may precipitate a suicidal imbal-ance in a vulnerable person due to the adverse life event as a stress-or and the broken social network as a loss of social support.Contents
4.15.1 Epidemiology and causes of suicide
 4.15.2 Deliberate self-harm: epidemiology 
and risk factors
 4.15.3 Biological aspects of suicidal behaviour
 4.15.4 Treatment of suicide attempters andprevention of suicide and attemptedsuicide

SECTION 4  clinical syndromes of adult psychiatry 952
The treating personnel and relatives of the suicide victim tend
to overemphasize the meaning of the most recent events in the 
course of the suicide process. A precipitating factor may well be 
decisive in explaining the precise timing of suicide in the long 
course of a person’s suicide process. Often, however, it also allows
a simple and rational explanation in the face of the complexity
of suicide.
The choice of a speciﬁ  c method takes place at the very end of the 
suicide process and represents the last possibility to intervene. 
Hanging is universally available and it is the most common suicide 
method globally. In many countries the ready access to ﬁ  rearms 
makes them potentially dangerous, especially among male adoles-
cents and young adults. Restricting access to handguns might be 
expected to reduce the suicide rate of young people. Previously, 
domestic gas was frequently used as a suicide method, and detoxﬁ  -

cation resulted in a signiﬁ  cant decrease in suicide rates. Nowadays, 
the increasing suicide rate in many Asian societies has been largely 
linked with pesticides and other poisons. Restrictive availability of 
lethal measures may also be important in the clinical treatment of 
individual suicidal patients. Restriction in availability of dangerous 
means is a strategy based on the fact that suicidal crises are often 
brief, suicidal acts are often impulsive, and the long-term suicide 
rate of serious suicide attempts is remarkably low.(4–6)
Firearms, carbon monoxide, and hanging are active suicide 
methods with the highest potential to cause death. Jumping from a 
height or leaping in the front of a moving vehicle are more passive

height or leaping in the front of a moving vehicle are more passive 
ways, but are also highly damaging in nature. Poisoning, drowning, 
or wrist cutting are typically methods which leave more time for 
help seeking and intervention.
Imitation means learning the use of a speciﬁ  c suicide method 
from a model which is overtly available in a culture, community, 
institution, or mass media. Imitation may have a signiﬁ  cant effect on the choice of a suicide method, especially at schools, in psychi-
atric hospital wards, and in the general population of young 
people. The most famous example of imitation is the effect of 
Goethe’s novel The Sorrows of Young Werther , which was wide-
ly read in Europe about 200 years ago. The suicide of the hero 
was imitated to such an extent that authorities in several

was imitated to such an extent that authorities in several 
European countries banned the novel. The ‘Werther effect’ also 
appeared after the death of Marilyn Monroe; the suicide rate 
rose about 10 per cent over the next 10 days. Recommendations 
for reporting of suicide have encouraged avoidance of repeti-
tive and excessive reports, descriptions of technical details, 
simplified explanations for suicide, presenting suicide as 
means of coping with personal problems, or glorifying suicide 
victims.(7)
Most suicides are solitary and private, but a few result from 
a pact between people to die together. Suicide pacts are exceptional, 
accounting for less than 1 per cent of all suicides.
Suicide always has a major impact on the survivors. Suicide is a 
threatening event not only among close family members, but also

threatening event not only among close family members, but also 
in the surrounding population, including treating personnel and 
the people at the victim’s workplace. The major challenges after 
a suicide, in addition to a normal mourning process, are dealing 
with shame and guilt feelings, and the crisis of survivors. Sharing of 
the traumatic experience and social support should be arranged 
immediately and continued, if necessary, at least some months after 
the suicide.
Epidemiology and public health aspects 
of suicide
Every year one million people commit suicide, accounting for 1 to 
2 per cent of total global mortality. Suicide is a leading cause of 
premature death, especially among young adults. It is the ﬁ  fth 
highest cause of years of life lost in the developed world. In many 
westernized countries, suicide is a more frequent cause of death

westernized countries, suicide is a more frequent cause of death 
than trafﬁ  c accidents. According to World Health Organization 
(WHO ) statistics, the annual world-wide incidence of completed 
suicide was 16 per 100 000 persons in 2000. This means that 
globally one person commits suicide every minute. Suicide is 
estimated to represent two per cent of the total global burden of 
disease.
The long-term trend in suicide mortality has been increasing 
at least during the last 50 years. The rank order of suicide mortality 
in the European region in 2001 to 2003 shows that most of the 
countries with high suicide mortality are located in Eastern Europe 
(Table 4.15.1.1). Outside this region, suicide mortality has been 
high in Japan and China. Everywhere, the male suicide rate is 
clearly higher than the female rate; China is the only exception 
with a very high female suicide rate.

The suicide rate of elderly people has been higher than in the 
younger age groups almost universally. However, in many Western 
countries, the suicide rate for people aged 65 years and over has 
been declining for decades. This change is associated with the 
growth of the general well being and the better social and health 
services.
Traditionally the incidence of suicide has been low in the younger 
age group (15–24), but during the past 40 years the suicide rate has 
been rising in many Western countries, especially among young 
males.
Fig. 4.15.1.1 The suicide process model.

953
A long list of major public health concerns in the ﬁ  eld of suici-
dology has emerged:
X suicidal ideation and suicide attempts are surprisingly common 
in the general population
X the high rate of suicides among adolescents and young adultsX unemployment as a major risk factor for suicide
X easy access to lethal suicide methods such as psychotropic or 
analgesic drugs, guns, and motor vehicles
X high alcohol consumption and increasing substance misuse
X undertreatment of major psychiatric disorders such as depres-
sion and schizophrenia
X suicide models projected by the mass media.
These findings indicate that rapid growth and continuous 
changes in society are simultaneously causing instability and dis-turbing the development of integration. Some regions and groups of people are inevitably affected negatively by this development, and large numbers of people are thus moving towards a greater risk of suicide.
Determinants of suicide

Usually, suicide has no single cause. It is the endpoint of an indi-vidual process, in which several interacting determinants or risk factors can be identiﬁ  ed (Tables 4.15.1.2 and 4.15.1.3). Risk factors 
are by their nature cultural, social, situational, psychological, bio-logical, and even genetic.
(8)
(a) Cultural factors in suicide
Culture deﬁ  nes basic attitudes towards life and death, and also 
towards suicide in society. We still have stigma against suicide. A hundred years ago, suicide was illegal in many European coun-tries. Similarly, most churches overtly opposed suicide and allowed suicide victims to be buried only outside the cemetery. Religion was also a major integrating force between individuals and the community. In a modern secularized society, religion is still a Table 4.15.1.1  Suicide rates per 100 000 by country, 2001–2003
European legion Males Females
Lithuania 74.3 13.9

Russian Federation 69.3 11.9Belarus 63.3 10.3Kazakhstan 50.2 8.8Estonia 47.7 9.8
Ukraine 46.7 8.4
Latvia 45.0 9.7Hungary 44.9 12.0Finland 31.9 9.8Republic of Moldova 30.6 4.8Czech Republic 27.5 6.8Austria 27.1 9.3France 26.6 9.1
Poland 26.6 5.0
Switzerland 26.5 10.6Romania 23.9 4.7Slovakia 23.6 3.6Ireland 21.4 4.1Bulgaria 21.0 7.3Germany 20.4 7.0Iceland 19.6 5.6
Sweden 18.9 8.1
Portugal 18.9 4.9Luxembourg 18.5 3.5Norway 16.1 5.8Netherlands 12.7 5.9Spain 12.6 3.9Italy 11.1 3.3United Kingdom 10.8 3.1
TFYR Macedonia 9.5 4.0
Uzbekistan 9.3 3.1Malta 8.6 1.5Albania 4.7 3.3Greece 4.7 1.2Georgia 3.4 1.1Armenia 3.2 0.5Azerbaijan 1.8 0.5
Other
Japan 35.2 12.8
Republic of Korea 24.7 11.2China (Hong Kong SAR) 20.7 10.2Australia 20.1 5.3Canada 18.7 5.2United States of America 17.6 4.1Thailand 12.0 3.8Singapore 11.4 7.6
Kuwait 2.5 1.4
Table 4.15.1.2 Risk factors for suicide: sociodemographic variables
Gender Male
Age Elderly

Social status LowEducational status LowMarital status Unmarried, separated, divorced, widowedResidential status Living aloneEmployment status Unemployed, retired, insecure employmentEconomic status Weak (males)Profession Farmer, female doctor, student, sailorSpecial subpopulations Students, prisoners, immigrants, refugees, 
 religious sects
Special institutions Hospitals, prisons, armyRegion Uneven distribution locally by urban–rural, 
 residential, or subcultural area
Season and time Spring and autumn, weekend, evening, anniversaryLife events Adverse life events such as losses and separations, 
 criminal charges
Social support LowSocial integration Lacking4.15.1 epidemiology and causes of suicide

SECTION 4  clinical syndromes of adult psychiatry 954
meaningful and protective factor for many individuals in a suicidal 
crisis. Western culture has had a tendency to emphasize the individ-uals’s free will and the shouldering of responsibility for one’s life, while egoistic and anomic trends in society have intensiﬁ  ed and 
altruism has almost disappeared. Such changes may have increased the incidence of suicide in society. The cultural background of sui-cide is a deep structure inherited over generations. Cultural factors also prevent rapid changes in suicidal behaviour, which is evident among immigrants, whose mode and rate of suicide usually lie somewhere between the original and the host cultures.
(9)
(b) Sociological theories on suicide

(9)
Classic sociology views suicide as a social, not an individual, phenomenon. The suicide victim’s moral predisposition to commit suicide, not his or her individual experiences, is felt to be the crucial factor. Moral predisposition means the degree to whichthe victim is involved in more or less integrated groups and in the values of those groups. Suicides are seen as a disturbance or symp-tom of a relationship between society and individuals. In 1897, Durkheim published his famous work on suicide and described four basic types. Anomic suicide reﬂ  ects a situation where an 
individual is no longer guided by the society due to its weakness, like the suicide of an unemployed and rejected alcoholic without any support from society. Altruistic suicide is illustrated by a society which can exert a strong inﬂ  uence on an individual’s decision to 
sacriﬁ  ce his or her life, as did the captain of the Titanic , for exam-

ple. Egoistic suicide is an individualistic decision of a person no 
longer dependent on others’ control or opinion such as a person who has arranged an assisted suicide. Fatalistic suicide is seen as a result of strict rules in a society which have proved decisive for the destiny of an individual, for example the suicide of a person held as a slave.
(10) There are also newer social theories of suicide 
which stress more the joint effects of social factors. The concept of social isolation has been clinically useful in understanding the socio-ecological and social-psychiatric background of suicide.
(11)
Some sociologists have underlined the individual meanings associ-ated with suicide.
(c) Life events and social support

(11)
The life situation preceding suicide is typically characterized by an excess of adverse life events and recent stressors. Usually, the sum effect of events is overwhelming and more important than a single 
life event. Job problems, family discord, somatic illness, ﬁ  nancial 
trouble, unemployment, separation, and death and illness in the family are the most common life events preceding suicide. Somatic illness and retirement are age-speciﬁ  cally connected with the 
suicides of elderly men, while separation, ﬁ  nancial troubles, job 
problems, and unemployment are more common among younger men. Severely disabling somatic illness is a very important risk factor for suicide in elderly male patients. In general, suicide among men is more often related to recent stressors than it is among women.
In most cases, life events are not accidental, but are usually also

In most cases, life events are not accidental, but are usually also 
dependent on the individual’s own behaviour. Personality features, even mental disorders, often explain the difﬁ  culties the victim has 
had. Among male alcoholics, life stress is connected with family discord and separations in all age groups. Other sources of stress in alcoholic male suicides are unemployment and ﬁ  nancial troubles, 
whereas in depressive non-alcoholic male victims life stress is associated more with somatic illness. Among alcoholic males, adverse life events and living alone clearly have an enhancing effect on suicidality. Among females, life events as psychosocial stress are less strongly connected with suicide. Depression and adverse interpersonal life events are more frequent contributors to female than male suicides.
(12)
(d) Psychology of suicide

(12)
Early psychological theories of suicide focussed on the concept of the self. A classical example is Freud’s theory assuming that self-destructive behaviour in depression represents aggression directed against a part of the self that has incorporated a loss or rejection of a love object. In his later theory of suicide, Freud presented the construction of the dual instincts, where Eros is a life-sustaining and life-enhancing drive in constant interaction with Thanatos, the aggressive death instinct.
Later psychodynamic thinking on suicide focussed more on the 
self in relation to others. Failures in the developmental and adapta-tional processes are reﬂ  ected in negative self-images and distorted 
cognitive schemas, leading to such feelings as depression, hopeless-ness, rage, shame, guilt, and anxiety. It is widely held that psycho-logical pain is found as a common element at the core of all suicidal

behaviours; suicide occurs when the individual can no longer endure the pain. Most recent psychological theories of suicide 
accept a multifactorial causation of suicide resulting from an inter-action of predisposing and precipitating factors.
(13) A person moves 
towards a suicidal crisis depending on the stressors and presence or 
absence of protective factors in his or her life.
(e) Neurobiological determinants of suicide
Suicidal behaviour is highly familial. Relatives of patients who commit suicide are themselves more likely to commit suicide than relatives of patients who do not commit suicide. Liability to suicidal behaviour may be a familially transmitted trait which is partly independent on the speciﬁ  c mental disorders. Since the 
heritability of liability to suicidal behaviour appears to be on the order of 30–50 per cent, interactions with environmental factors must also be signiﬁ  cant.
Results of adoption studies suggest that genetic factors rather

Results of adoption studies suggest that genetic factors rather 
than familial environmental factors are the determinants of famil-ial concordance for suicidal behaviour. Among biological relatives Table 4.15.1.3  Clinical determinants of suicide
Family history Suicidal behaviour, mental disorders
Mental disorders Any disorder, depression, substance use disorders, 
personality disorders, schizophrenia
Contact with psychiatric 
servicesAny contacts, recent contacts, post-discharge 
period, psychotropic drugs
Psychiatric symptoms Hopeless, helpless, depressive, psychotic, delirious, 
anxious, aggressive, introversive
Suicidal behaviour Previous suicide attempts, suicidal ideations, death 
wishes, indirect gestures
Physical health Severe physical illness such as cancer, AIDS, stroke, 
and epilepsy; permanent sickness
Availability of suicide 
methodsEasy access to lethal methods

955
of adopted suicide victims there is a higher incidence of suicide 
than among the relatives of non-suicide controls or among the adoptive relatives of the suicide victims. Also identical twins have a higher concordance for suicide, attempted suicide, and suicide ideation compared with non-identical twins.
(14)
The ﬁ  ndings that genetic factors contribute to suicidal behaviour 
has stimulated studies aimed at identifying susceptibility genes. So far molecular genetic studies have focussed on the serontonergic pathway. Two genes have emerged as being involved in the vulner-ability to suicidality: the tryptophan hydroxylase 1 (TPH1) gene, as a quantitative risk factor for suicidal behaviour, and serotonin transporter gene (5-HTTLPR), which is consistently associated with impulsive-aggressive personality traits.
(15) Patients who have 
seriously attempted suicide by violent means have low levels of the serotonin metabolite 5-hydroxyindole acetic acid in their cere-brospinal ﬂ  uid.

(16) These and other neurobiological changes are 
discussed in Chapter 4.15.3.
Basic characteristics of the suicide victim

Persons at greatest risk of suicide are usually middle-aged or older, non-married men with poor social and economic position, and a family history of mental disorders and suicidal behaviour. Usually they are living alone, and often unemployed or withinsecure employment. They also typically have marked recent life stress and a weak social network. Most suffer from depression, and feel hopeless and many have a comorbid substance abuse orpersonality disorder. Almost all elderly victims have comorbid physical illness or are permanently disabled. Most have previously contacted health care, and communicated their suicidal tendencies at least indirectly, although usually without receiving adequatepsychiatric treatment. Half of them have previously attemptedsuicide.
Mental disorders and suicide
Virtually all mental disorders carry an increased risk of suicide.(17)

The suicide risk in functional mental disorders is double that in substance use disorders, which in turn carry double the risk of suicide compared to organic disorders. The greatest risk of suicide among all clinical states is in attempted suicide, which carries about 40 times the expected value (Table 4.15.1.4). In anorexia nervosa and major depression, the risk is about 20-fold, and in other mood disorders and psychoses about 10 to 15 times higher than expected. In anxiety, personality, and substance use disorders the suicide risk is at lower levels, but about 5 to 10 times higher than the expected value. In subtance disorders the risk is dependent on the type of disorder, being clearly lowest in alcohol, cannabis, and nicotine abusers.
(17)
Psychological autopsy studies have been used to construct an

(17)
Psychological autopsy studies have been used to construct an 
overall view of suicide by collecting all available relevant informa-tion on the victim’s life preceding his or her death. In psychological autopsy studies, mental disorders of suicide victims have been assessed using DSM-diagnoses and large unselected samples. In two recent meta-analyses
(18,19) the victim received at least one 
diagnosis on Axis I in 87 to 90 per cent of the suicides. In all studies, depressive disorders (43 per cent) and substance use disorders (26 per cent), personality disorders (16 per cent) and psychoses (9 per cent) were frequent and comorbidity was common.In two European psychological autopsy studies
(20,21) from

(20,21) from 
Finland and Northern Ireland, the distribution of the principal diagnoses was similar (Table 4.15.1.5). The most common psychiatric diagnoses in suicide were major depression and alcohol dependence. Major mood disorders together comprised 42 to 36 per cent and substance use disorders, 19 to 30 per cent of all suicides. Comorbidity was a major ﬁ  nding in both samples, most commonly substance 
use disorder with major depression. A recent European psychologi-cal autopsy study gave similar results underlining, however, the role of personality disorders as a risk factor for suicide.
(22)Table 4.15.1.4  Rank order of suicide in mental disorders
Suicide attempt
Anorexia nervosaMajor depressionMood disorders not otherwise speciﬁ  edReactive psychosesBipolar disorderDysthymiaSchizophreniaAnxiety disordersPersonality disordersSubstance use disorders
Table 4.15.1.5  Principal diagnoses of suicide victims in Finland and 
Northern Ireland
Diagnosis Finland (%) 
(n = 229)Northern

(n = 229)Northern 
Ireland (%) 
(n = 118)
Major depression 30 31
Depressive disorder not otherwise speciﬁ  ed 9 —Dysthymia — 1Bipolar disorder 3 4Alcohol dependence 17 24Alcohol misuse 2 4Other substance use disorders — 2Schizophrenia 7 6Schizoaffective disorder 3 1Other psychoses 3 4Anxiety disorders 1 5Adjustment disorder 3 3Organic mental disorders 2 1Other Axis I disorders 2 2Personality disorder 9 3No diagnosis 2 10Insufﬁ  cient information for assessment 7 —4.15.1 epidemiology and causes of suicide

SECTION 4  clinical syndromes of adult psychiatry 956
The mortality risk for suicide in major depression is 20 times 
that expected, and 15-to 20-fold in all affective disorders. Every sixth death among depressive people treated as psychiatric patients is by suicide.
(23) The risk of suicide varies across the subclasses of 
depression, and is related to the selection of suicidal patients for the various types of treatment. The risk is highest for depressive inpatients, even during the postdischarge period, and much lower among psychiatric outpatients, although clearly lowest for those treated for depression in primary care.
(24) A meta-analysis found 
a hierarchy of life-time suicide prevalence: eight per cent in people ever admitted for suicidality, four per cent in patients admitted with affective disorder but not for suicidality, and two per cent in mixed inpatient and outpatient populations.
(24)
Depression of suicide victims differ qualitatively from that of

(24)
Depression of suicide victims differ qualitatively from that of 
living controls; it seems to be more severe and accompanied more often by insomnia, weight or appetite loss, feelings of worthlessness, inappropriate guilt, and thoughts of death or suicidal ideation.
(26)
In addition, impulsive and aggressive behaviour, alcohol and drug abuse and dependence, and cluster B personality disorders increase the risk of suicide in individuals with major depression.
(27)
Inadequate and inefﬁ  cient antidepressant treatment of depressed 
suicide victims has been a persistent ﬁ  nding in several studies. Less 
than half of suicide victims with major depression have been in contact with psychiatric care at the time of suicide. However, there is some evidence that good monitoring and maintenance treatment in high-risk groups of patients may be able to decrease their suicide rates.
(28)
Alcohol and drugs, often combined, are a major risk or a precipi-

(28)
tating factor for suicide. They may intensify the suicidal intent, offer a constantly available suicide method, worsen the somatic status of the victim, and increase the risk of complications after the attempt. Alcohol and drugs impair judgement and lower the threshold to suicide. Alcohol is detected in about every third case at the moment of suicide.
(29) The lifetime risk of suicide has
been estimated at 7 per cent for alcohol dependence, with only slight variation over the life.
(30) The suicide rate in heavy drinking 
is 3.5 times and in alcohol use disorders ten times higher thanthat in the general population.
(31) In drug dependence or abuse
it is 15 times higher than expected.(17,31)  The role of substance
use disorders varies greatly by country. In a recent study from Estonia, alcohol dependence was found in a half of suicidevictims.
(32)
The suicide risk in schizophrenia appears to be almost 10 times

(32)
The suicide risk in schizophrenia appears to be almost 10 times 
higher than in the general population.(17) The lifetime risk of sui-
cide in schizophrenia is estimated to be 5 per cent.(30,33)  The great 
majority of schizophrenic patients commit suicide in the active phase of the disorder after having suffered depressive symptoms. Suicide in schizophrenia is thus less of a surprise; it is typically preceded by a previous attempt, and suicidal intent has been com-municated at least as often as in non-schizophrenic suicides.
(34)
Schizophrenic suicide victims differ from other schizophrenic patients by having suicidal thoughts and previous suicide attempts, being more depressive, and having more positive symptoms.
(35)

(34)
(35)
Undertreatment, comorbidity, treatment non-compliance, and a high frequency of non-responders are also common problems among schizophrenic suicide victims. Adequacy of comprehensive care is crucial for suicide prevention in schizophrenia, especially among actively psychotic patients with recent suicidal behaviour and depressive symptoms.
(36)Personality disorders are tightly connected with suicide. Most
of the suicide victims with personality disorder, especially with borderline and emotionally unstable personality disorder, havealso comorbid depressive disorder or substance abuse. Theyoften suffer from impulsive and aggressive behaviour.
(20,22,27,38)
This kind of comorbidity is very frequent among the young suicide victims.
Mental disorders, particularly depressive disorders, substance

Mental disorders, particularly depressive disorders, substance 
abuse, and antisocial behaviour have an important role in the ado-lescent suicides. The diagnostic distribution of mental disorders among them is surprisingly similar to that of the young and even middle-aged adults.
(39)
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disorders in adolescent suicide: DSM-III-R axes I and II diagnoses in suicides among 13- to 19-year-olds in Finland. Archives of General 
Psychiatry ,48, 834–9.4.15.2 Deliberate self-harm: 
epidemiology and risk factors
Deliberate self-harm (DSH) refers to behaviour through which 
people deliberately inﬂ  ict acute harm upon themselves, poison

people deliberately inﬂ  ict acute harm upon themselves, poison 
themselves, or try do so, with non-fatal outcome. These behaviours are somehow linked to, but do not result in, death. Common to these behaviours is that they occur in conditions of emotional tur-moil. In former days these behaviours were often regarded as failed suicides. However, this view did not appear to be correct, and the great majority of patients in fact do not try to kill themselves. Therefore, the term deliberate self-harm was introduced to describe the behaviour without implying any speciﬁ  c motive.
(1) But this too 
has some disadvantages because there is a temporal association between non-fatal and fatal suicidal behaviour; many people who die by suicide have engaged in DSH before. Thus, Kreitman et al.
(2)
introduced the concept of parasuicide to describe behaviour that,

(2)
introduced the concept of parasuicide to describe behaviour that, 
mostly without the intention to kill oneself, communicates a degree of suicidal intent. However, both terms, deliberate self-harm and parasuicide, are still somewhat confusing, because in practice they include people who really have the intent of killing themselves but survive the attempt. The difﬁ  culty of ﬁ  nding a good terminology for 
these behaviours is reﬂ  ected in differences in research populations in 
empirical studies: some studies are limited to self-poisoning only (overdose), a few studies are restricted to self-injury (wrist cutting) only, some to self-poisoning and self-injury combined, and some studies include behaviours in which, due to last-moment interven-tion from others, there was no actual self-harm inﬂ  icted at all. In 
recent years the term self-harm is being used in the United Kingdom

recent years the term self-harm is being used in the United Kingdom 
and North America since the adjective ‘deliberate’ is not favoured by patients, particularly those who repeatedly engage in acts of self-harm.
(3)
In this chapter, we will use the term deliberate self-harm inter-

(3)
changeably with attempted suicide to refer to non-fatal suicidal behaviours in which there may have been an intention to die, however ambiguous this intention may have been, and irrespec-tive of other intentions that may have been operating at the same time. It should be stressed that in deliberate self-harm many motives may play a role simultaneously, even contradictory motives such as the hope of being rescued and the wish tocontinue living. Intentions may vary from attention seeking or communication of despair, appeal for help, to a means for stress reduction. Common to these behaviours is that they are motivat-ed by change: people want to bring about changes in their present situation through the actual or intended harm or unconscious-ness inﬂ  icted upon the body. Deliberate self-harm may be deﬁ  ned 
as follows.
(4)

(4)
An act with non-fatal outcome, in which an individual deliberately initiates a non-habitual behaviour that, without intervention from others, will cause self-harm, or deliberately ingests a substance in excess of the prescribed or generally recognised therapeutic dosage, and which is aimed at realising changes which the subject desired via the actual or expected physical consequences.4.15.2 deliberate self-harm: epidemiology and risk factors

SECTION 4  clinical syndromes of adult psychiatry 958
This deﬁ  nition covers deliberate non-fatal suicidal behaviours. 
Not included are accidental cases of self-poisoning, accidental overdoses of opiates, or self-harmful acts by persons who do not anticipate the consequences of their actions. It does not include automutilation, which is an habitual, often obsessive act of inﬂ  ict-
ing (minor) self-harm, mostly without a conscious intent of chang-ing the present situation, as with certain persons with learning disability.

Deliberate self-harm can have very different motivations, varying from an intention to die to a cry for help. These behaviours may be well prepared or carried out impulsively, and may have different physical consequences. The degree of lethality and the degree of medical seriousness of the consequences thus depend upon intention, preparation, knowledge and expectations of the method chosen, and sometimes upon coincidental factors such as interven-tion from others.
It is often difﬁ  cult to assess the true intent of DSH. Because of

It is often difﬁ  cult to assess the true intent of DSH. Because of 
fear for consequences, such as admission to a psychiatric hospital, or because of psychological defence mechanisms, people some-times deny or conceal their intention to die. They also may exag-gerate their intention to die in order to receive help. Sometimes people engage in potentially highly lethal self-harming behaviour 
without any wish to die, for example when they do not have 
adequate knowledge of the medication used. People who present at a general hospital with minor self-injury or minor self-poisoning 
may have had strong intentions to die but had insufﬁ  cient knowl-
edge of the lethality of the method. Therefore, one cannot always reliably infer what the precise meaning of the behaviour was, either from its overt characteristics or from the person’s self-report. Among a large sample of adolescents aged 15 and 16 years, Rodham et al . found that adolescents who took an overdose more often

expressed a wish to die compared to those who engaged in self-cutting.
(5) Motives associated with self-cutting were self-
punishment and interruption, i.e. trying to get relief from a terrible state of mind.
In the 1960s and 1970s, there was a sharp increase in the number of people treated in hospitals in Europe, the United States and Australia because of intentional overdoses or self-injury. In the 1980s several studies showed a stabilization.
(6,7) In the early 1990s 
these numbers increased further in some regions.(8,9) The absolute 
number of persons treated for deliberate self-harm in general hos-pitals, however, does not adequately reﬂ  ect the size of the problem.

number of persons treated for deliberate self-harm in general hos-pitals, however, does not adequately reﬂ  ect the size of the problem. 
These numbers should be calculated against the size and the char-acteristics of the population in the areas that are being served by the hospitals. Furthermore, in some countries DSH patients are treated by general practitioners when there is no need for hospital admission. In many instances emergency attendance for overdos-ing is not even registered. Except for Ireland, where a National Registry of Deliberate Self-Harm has been established,
(10) there are 
no national registries that reliably monitor trends in DSH treated in general hospitals. Even though DSH is considered a major prob-lem in the United States, clinical epidemiological research into DSH is uncommon.
(11) Also, few epidemiological studies on DSH 
originate from other parts of the world.Changes over time

In Edinburgh and Oxford, in the United Kingdom, there has been continuous monitoring of deliberate self-harm over a long period of time, where characteristics of persons engaging in DSH have 
been related to the corresponding population.
(7,12,13) In these two 
cities trends in DSH rates have been documented reliably. After a period of stabilization in the 1980s a marked increase was observed. Between 1985 and 1995 the rates of DSH in Oxford increased by 62 per cent in males and 42 per cent in females. The increase in DSH has been most marked among young males. A similar trend has been observed in North Worcestershire where hospital referred cases of DSH were monitored over a period of 20 years (1981–2000).
(14)
In Canada, the DSH rate was estimated to be around 304 
per 100 000.(15) In the United States National Institute of Mental

(14)
per 100 000.(15) In the United States National Institute of Mental 
Health’s Epidemiological Catchment Area study (1980–1985) it was found that 2.9 per cent of the respondents had engaged in DSH at some point of time.
(16)
So far only one international multicentre study into deliberate 
self-harm has been conducted taking into consideration the methodological pitfalls outlined above. The World Health Organization (WHO) initiated a collaborative multicentre study in 16 regions in Europe using the same methodology, deﬁ  nition, and 
case-ﬁ  nding criteria.
(9,17) The ﬁ  ndings were related to the size and 
characteristics of the corresponding general population in order to investigate rates, trends, risk factors, and social indicators. Most of the epidemiological data presented here have been drawn from that study.
(9,18)
Differences between countries and regions

(9,18)
There is widespread variation between countries with regard to rates of deliberate self-harm. Based on the latest available data for the years 1995–1999, overall, DSH rates (person-based) were highest in the United Kingdom (Oxford), Belgium (Ghent), Hungary (Pecs) and Finland (Helsinki), with female rates per 100 000 ranging from 83 in Padova (Italy) to 433 in Oxford. Male DSH rates per 100 000 ranged from 53 in Umea (Sweden) to 337 in Oxford.
(9) Looking at trends over time, an average decrease

(9) Looking at trends over time, an average decrease 
for male DSH rates of 13 per cent was found comparing average person-based rates for 1989/1993 to the period 1995/1999, with the greatest reduction (70 per cent) in Innsbruck (Austria). For female DSH rates the average decrease in the same period was lower (4 per cent), with the greatest reduction (31 per cent) in Sor-Trondelag (Norway). In addition to medically referred cases of deliberate self-harm, community-based studies show that an even higher propor-tion of DSH appears to be ‘hidden’ from health care services.
(19)
Differences between catchment areas in deliberate self-harm 
rates in the WHO/EURO study have been studied in relation to socio-economic characteristics of these areas.
(9,20)  No correlations 
were found with most of the social and economical factors supposedly related to DSH, such as population density, urban–rural distribution, proportion working in agriculture forestry or ﬁ  shery,

were found with most of the social and economical factors supposedly related to DSH, such as population density, urban–rural distribution, proportion working in agriculture forestry or ﬁ  shery, 
sex ratio, percentage aged 40 and over, number of people per house-hold, percentage people living alone, percentage single parent families, per capita income, unemployment rate, life expectancy, mortality rate, infant mortality, crimes per year per 1000, and per capita alcohol consumption. Only two characteristics of the catchment areas seemed to be related to DSH rates: the percentage

959
of divorced people in the area and the percentage receiving social 
security. Family stability and the percentage of the population rely-ing on welfare both seem to be related to the frequency of DSH, but the interpretation of these ﬁ  ndings is difﬁ  cult because one would 
expect the other related social indicators of societal cohesion to covary as well.
It is important, however, to realize that the characteristics 
mentioned above relate to regions or countries, and do not relate to individuals. At individual level, characteristics such as unem-ployment play an important role, but this does not mean that unemployment rates do explain high DSH rates in a region.
(21,22)
This relationship holds only for some regions and not for others, as is documented repeatedly.
(23) The effect of exposure to risks factors

(21,22)
(23) The effect of exposure to risks factors 
may be due to contextual effects, which arise if individuals’ risks of suicidal behaviour depends not only on their personal exposure to risk or protective factors, but also on how these are distributed in their social, cultural or economic environments.
(24,25) In a small 
area study in South East London, Neeleman et al . found that the 
DSH rate of minority groups relative to the white group was low in some areas and high in other areas.
Cultural variation in DSH has been documented from India,
(26)
Sri Lanka,(27) and Pakistan,(28) and from ethnic groups within 
Western societies, such as the Inuit in Canada.(29) Neeleman 
et al.(30) studied ethnic differences in DSH in Camberwell, London, 
and found considerable differences between the DSH rates for white people and for British-born Indian females and African-Caribbeans.

(30) Indian females had a particularly high rate, 
7.8 times that of white females. Marriage problems seem to be related to DSH in Asian countries such as India, Pakistan, Sri Lanka, and China. Y oung married women may have serious difﬁ  culties 
after moving in with their husbands’ extended families. Dowry problems and problems with in-laws are thought to be precipitants of attempted suicide among young married women. In Asian coun-tries the methods used in DSH reﬂ  ect differences in accessibility. 
Self-poisoning with organophosphate pesticides and other house-hold poisons is prevalent. As in the Western world DSH appears to reﬂ ect feelings of hopelessness and helplessness in adverse living

Self-poisoning with organophosphate pesticides and other house-hold poisons is prevalent. As in the Western world DSH appears to reﬂ ect feelings of hopelessness and helplessness in adverse living 
conditions with no prospect of improvement. Women tend to be more powerless to bring about changes in their living conditions. In Sri Lanka, the continuous warfare, poverty, and the lack of 
opportunities at home and abroad frustrates the young who are 
relatively well educated.
(27)
Sex and age
In all but one centre (Helsinki) of the WHO Multicentre Study on Suicidal Behaviour the female DSH rates were higher than the male rates. Across the participating regions, on average, the rates for females were 1.5 times higher than those for men. DSH rates were consistently higher among those in the young age groups, with the highest person-based male DSH rates in the age group 25–34 years, whereas for females in most centres the highest rates were found in the age group 15–24 years.
(9)

(9)
Sociodemographic characteristics
Single and divorced people were over-represented among people who engaged in DSH in the WHO/EURO study.
(9,18) Nearly half 
of the males and 38 per cent of the females were never married. An interaction effect was found for age in that the proportion of single persons among those engaging in deliberate self-harm 
reduced with increasing age, whereas the proportion of divorced, separated, and widowed people increased with age. Among deliber-ate self-harm patients who were economically active, a high percentage was unemployed. Based on average DSH rates over the period 1995–1999, 26 per cent of the males and 14 per cent of the females were unemployed.
(9)
These ﬁ  ndings are consistent with outcomes of earlier research 
conducted in the United Kingdom, where socio-economic depriva-tion (low social class and unemployment) repeatedly appear as characteristics of the DSH populations.
(22)
These ﬁ  ndings indicate that DSH patients disproportionately

(22)
These ﬁ  ndings indicate that DSH patients disproportionately 
have had low education, and have high levels of unemployment, poverty, and divorce. The ﬁ  ndings may be partly related to under-
lying common causes, such as the presence of psychiatric disorders, but they also suggest the inﬂ  uence of sociological factors impacting 
on a relatively economically deprived group in society with a greater share of adversity.
(24) Socio-economic deprivation is a well-
established determinant of psychiatric morbidity and DSH.(32,33)
In contrast with completed suicide, where the presence of psychiat-ric disorders is well documented (up to 95 per cent of suicides may have suffered from a psychiatric disorder), psychiatric disorders are much less frequent among those who deliberately harm themselves. Among those who engage in DSH for the ﬁ  rst time in their lives, 
the prevalence of psychiatric disorders may be rather low; among repeaters, psychiatric morbidity is considerable.
(34,35)

(34,35)
Methods
Methods used in deliberate self-harm are mostly ‘non-violent’ . In the WHO Multicentre Study, 65 per cent of males and 82 per cent of females took an overdose, based on average DSH rates for the period 1995–1999. Cutting, mostly wrist cutting, was employed in 16 per cent of male cases and 9 per cent of female cases. There are some differences between European countries in the use of particular methods. Based on the years 1995–1999, a relatively high percentage of self-cutting was found in Tallinn (Estonia, 50 per cent), Ljubljana (Slovenia, 30 per cent), and Innsbruck (Austria, 26 per cent). In Szeged (Hungary), 19 per cent of males and 15 per cent of females used poisoning with pesticides, herbicides, or other toxic agricultural chemicals, whereas in other regions this ranged from 0–3 per cent.
(9) In Sor-Trondelag, Norway, higher percentages

(9) In Sor-Trondelag, Norway, higher percentages 
engaged in DSH by deliberate alcohol overdose (6 per cent of males and 5 per cent of females). In general, somewhat older men used the method of jumping or jumping in front of a moving object. In the Oxford studies between 1985 and 1995, 88 per cent of all episodes involved self-poisoning, 8 per cent involved self-injury, and 4 per cent involved both. There was an increase in the use of paracetamol from 31 per cent of poisoning cases in 1985 to 50 per cent in 1995.
(6) There was also an increase in antidepressant 
overdoses and a decrease in overdoses of minor tranquillizers and sedatives. Comparing the early 1990s with the late 1990s, a slight increase was observed in overdose by medication.
(9) For all regions 
the methods used in DSH acts did not covary significantly with age.
The differences in methods between countries may be related to

The differences in methods between countries may be related to 
differences in the accessibility of certain methods. Until 1998 paracetamol was available in large quantities in the United Kingdom, unlike other European countries.
(36,37) The ingestion of 4.15.2 deliberate self-harm: epidemiology and risk factors

SECTION 4  clinical syndromes of adult psychiatry 960
alcohol during or before the act sometimes can be considered to be 
a part of the actual method of DSH (when used to bring about unconsciousness, or to increase the risk of a fatal outcome), as part of the preparation (to lower the threshold for engaging in an act of DSH, because of disinhibition), or as a long-term risk factor. Hawton et al .
(38,39) found that 22 to 26 per cent of DSH patients 
had consumed alcohol at the time of the act (males more frequent than females), and that 44 to 50 per cent had consumed alcohol during the 6 h before the DSH acts, this again being more common in males than in females. About 28 per cent of DSH patients in Oxford appeared to be substance misusers (alcohol and drugs).
General population self-report surveys
General population epidemiological surveys of adolescents indicate that DSH acts occur more frequently than suggested by hospital statistics.

(40,41) A number of surveys have been conducted 
to estimate the prevalence of DSH. Most of these surveys concerned adolescents and were administered anonymously. Most question-naire studies revealed that between 1 and 20 per cent of respon-dents had engaged in DSH at some point in time.
(41–44) However, 
the methodology used in the various studies varies considerably and therefore limits comparison of the outcomes. In the study by Hawton et al.
(41) a minority (12.6 per cent) of adolescents who 
had engaged in DSH had presented to hospital.
Lifetime prevalence
Based upon the rates from the WHO/EURO study the lifetime prevalence of deliberate self-harm should be around 3 per cent for females and 2 per cent for males, with some variations between countries and regions.

(9) DSH acts that did not lead to medical 
treatment at a hospital or general practitioner’s surgery are very difﬁ cult to study, because of the limited validity of self-report data. 
Based on two large community-based surveys, the lifetime preva-lence of suicidal ideation varied from 2.6 to 25.4 per cent and for deliberate self-harm this varied from 0.4 to 4.2 per cent.
(45,46)
As previously mentioned, there is a considerable variety of 
behaviours within the broad category of non-fatal suicidal behaviour. A review of classiﬁ  cation studies
(34) revealed three types 
of DSH patients: a ‘mild’ type, a ‘severe’ type, and a ‘mixed’ type in between.
The mild type of DSH encompasses mostly relatively non-

violent methods followed by non-serious physical injury. Y oung age, living together, few precautions to prevent discovery, low level of suicidal preoccupation, low suicidal intent, interpersonal moti-vation are all characteristics associated with mild forms of attempted suicide/deliberate self-harm. The severe category consists mostly of relatively hard methods followed by serious physical consequences. Older age (over 40), many precautions to prevent discovery, high level of suicidal preoccupation, high suicidal intent, self-directed motivation, often relocated, previous attempted suicides, depres-sion, drug dependence, a high degree of overall dysfunctioning, 
poor physical health, and previous psychiatric treatment are all

poor physical health, and previous psychiatric treatment are all 
characteristics associated with the concept of ‘severe’ deliberate self-harm. The risk of repetition is greater in the severe type. In between, in the mixed type of DSH, the DSH acts and patients involved show mixed characteristics, which makes this type harder 
to identify in medical practice.
In order to further reﬁ  ne the classiﬁ  cation of deliberate self-
harm, Arensman
(47) included psychological and personal history 
variables and these characteristics were studied in relation to recur-rent DSH in a follow-up period of 1 year. The mild DSH type  was

variables and these characteristics were studied in relation to recur-rent DSH in a follow-up period of 1 year. The mild DSH type  was 
validated, approximately 40 per cent of the total sample, as being predominantly younger than 30 years of age, single, living alone or with parents, and having minor injuries because of the index attempt. The mean number of previous DSH acts was 3.7. The rep-etition rate in the follow-up period for this group was 27 per cent. In the older age group, two groups were distinguished: a moderate group and a group with an extremely high risk for non-fatal repetition were identified. The high-risk group, consisting of approximately 28 per cent of the total sample, suffered more physical injury as a consequence of their deliberate self-harm.
The high-risk group  consisted predominantly of females in the

The high-risk group  consisted predominantly of females in the 
age group 30 to 49 years who were divorced or separated, living alone, and who were economically inactive. Most of them had engaged in previous DSH acts (mean number: 5). They had histo-ries of traumatic life events that mostly started early in life. The high-risk group showed the highest scores on depression, hopeless-ness and expression of state-anger, and two-thirds were diagnosed as having borderline personality disorder. In the follow-up at least 75 per cent engaged in repeated DSH.
The moderate group  was characterized by low levels of physical 
injury following their DSH, they were predominantly aged at least 30 years and married, and scored intermediate on measures of depression, hopelessness, and anger. The mean number of previous attempts was 2.3, and 33 per cent made one or more repeated DSH acts in the follow-up. Surprisingly, this classiﬁ  cation into three

types of non-fatal suicidal behaviours did not correspond to the levels of reported suicide intent nor to the levels of the different motivations reported (to die, to appeal, to lose consciousness, revenge), underlining the difﬁ  culty of classifying DSH according to 
intentions. Rodham et al.
(5) found evidence for different subgroups 
of DSH patients based on DSH methods and motives. For example, they identiﬁ  ed a subgroup of female adolescents who engaged in 
self-cutting and who reported self-punishment  as the primary 
motive, followed by trying to get relief from a terrible state of mind .
Furthermore, wish to die  as a motive was signiﬁ  cantly more often 
reported by those who took an overdose compared with those who engaged in self-cutting.
Aetiology

Aetiology
The last psychological step towards deliberate self-harm is always set in conditions of emotional turmoil, an emotional crisis. Essential in crisis is the absence of any positive outlook towards the future. People completing suicide do not expect any improvement of their situation in the near or distant future. People who engage in delib-erate self-harm indicate that their future is hopeless, but they still seem to have a faint hope, however ambiguous this may be, that the future might improve. In this way deliberate self-harm may be con-ceived as a self-invented form of crisis intervention. Studies into the cognitive functioning of DSH patients indeed show a global and stable form of negative anticipations and absence of positive anticipations towards the future, probably as a conse-quence of disturbances in their autobiographical memory, i.e. an

961
overgeneral memory.(48,49) Whenever these anticipations remain 
overgenerally negative after an act of DSH, it is likely that hopeless-ness will increase and that this behaviour will occur again.
(50)
Precipitants
Difﬁ culties or conﬂ  icts that may bring the person to believe that his 
or her future is without hope can trigger the psychological crisis resulting in deliberate self-harm. DSH is often precipitated by disharmony with key ﬁ  gures, work-related problems, ﬁ  nancial 
difﬁ culties, or physical illnesses. Long-standing relationship prob-
lems or feelings of loneliness are especially common. People who engage in DSH have a weak social support system,
(48) and they 
report relational difﬁ  culties as major problems in life. They show 
deﬁ cits in interpersonal problem solving, and their future holds no

deﬁ cits in interpersonal problem solving, and their future holds no 
promise. Their emotional status can best be described as a state of learned helplessness, a situation of a blocked escape, in which no solution exists for a perceived insurmountable adversity.
(51) This 
leads to the question as to why these persons have developed such helpless attitudes.
Long-term vulnerability factors
The conﬂ  icts experienced by DSH patients in the days before an act 
of DSH are not different from the same conﬂ  icts they have experi-
enced over and over again. Not only recent life events, but also the 
life events that occurred in their past are important.(47) Many DSH

life events that occurred in their past are important.(47) Many DSH 
patients, males as well as females, have had traumatic childhood experiences, including physical and emotional neglect, broken homes, other unstable parental conditions, violence, sexual and physical abuse, incest, parents who had psychiatric treatment, who were alcoholics and/or addicted to opiates. Women who have been abused have a much greater probability of becoming a repeater later. In addition they often develop poor relationships, lack self-esteem, and experience overwhelming feelings of helplessness and hopelessness. Any trigger, for example an argument with a friend, may be sufﬁ  cient to provoke suicidal ideation and behaviour.
DSH patients not only suffer from helplessness with regard to 
interpersonal conﬂ  icts, they also tend to be powerless in other 
domains of life. The DSH population disproportionately consists

domains of life. The DSH population disproportionately consists 
of unemployed persons, from low social classes, with low educa-
tional levels, economically deprived, divorced, disabled, addicted, incarcerated, and/or lonely. Many have received in- or outpatient psychiatric treatment. These ﬁ  ndings are somewhat complicated by 
the fact that many of these vulnerability factors are strongly inter-
related. Unemployment, addiction, and unstable partnership
relations all may be caused by psychiatric diseases. For example, unemployment and DSH may both be a consequence of addiction. However, it is not fair to assume that most of the economic deprivation of suicidal patients is explained by their psychiatric condition. The considerable differences between nations in the prevalence of DSH support the importance of socio-economic 
conditions.

Repetition is one of the core characteristics of suicidal behaviour. 
Among those who die by suicide up to 40 per cent have a history of previous DSH acts.
(52) Among DSH patients ‘repeaters’ are more 
common than ‘ﬁ  rst-evers’ . Between 30 and 60 per cent of DSH 
patients engaged in previous acts, and between 15 and 25 per cent did so within the last year.
(3,7,53,54)Risk of suicide after deliberate self-harm
Prospectively, DSH patients have a high risk of dying by suicide. Between 10 and 15 per cent eventually die because of suicide.
(11,53)
The connection between DSH and suicide lies between 0.5 and 2 per cent after 1 year and above 5 per cent after 9 years.
(11)
Mortality by suicide is higher among DSH patients who have engaged in previous acts of DSH.
(55,56) The risk of suicide after 
deliberate self-harm for males is nearly twice the female risk, the risk being particularly high in the ﬁ  rst year.
(57,58) Alcohol and drug

(57,58) Alcohol and drug 
abuse and related social deterioration are risk factors for subse-quent suicide,
(59) as are psychiatric diagnosis (affective disorders, 
schizophrenia, personality disorders), and a highly lethal non-impulsive index act of DSH. In a large European study focusing on young deliberate self-harm patients, positive correlations were found between rates of DSH and suicide for both males and females, with a statistically signiﬁ  cant association among males 
aged 15–24.
(60)
Repetition of deliberate self-harm
Risk of repeated DSH is highest during the ﬁ  rst year after an act of 
DSH, and especially within the ﬁ  rst 3 to 6 months.(55,57,61)  In the

(60)
DSH, and especially within the ﬁ  rst 3 to 6 months.(55,57,61)  In the 
WHO/EURO Multicentre Study on Suicidal Behaviour it was found that at least 54 per cent of DSH patients had engaged in a DSH act before, 30 per cent at least twice. Prospectively, 30 per cent of DSH patients made at least one repeated attempt in a 1-year follow-up.
(62,63)
It is hoped for that knowledge of antecedents or risk factors may 
foster early identiﬁ  cation of persons at risk, and improvement

(62,63)
foster early identiﬁ  cation of persons at risk, and improvement 
of treatment. Many studies have tried to identify risk factors or antecedents and some of these by now are well known. Sociodemographic risk factors associated with repetition are belonging to the age group of 25 to 49 years, being divorced, unemployed, and coming from low social class. Psychosocialcharacteristics of repeaters are substance abuse, depression, hope-lessness, personality disorders, unstable living conditions/living alone, criminal records, previous psychiatric treatment, and ahistory of stressful traumatic life events, including broken homes and family violence, especially physical and mental maltreatment by partners. Prospectively, a history of previous attempts is oneof the most powerful predictors of future non-fatal suicide attempts.
(34,51,64,65)

Deliberate self-harm is a major problem in many contemporary societies. DSH seems to reﬂ  ect the degree of powerlessness and 
hopelessness of young people with low education, low income, unemployment, and difﬁ  culties in coping with life stress. As such, 
non-fatal suicidal behaviour should be a major concern for politi-cians. There are substantial differences between communities in the prevalence of deliberate self-harm. This suggests that some communities better meet the needs of their underprivileged young-sters than others do, but we barely understand the differences between communities and nations. Preventive action therefore is difﬁ cult to design. There is a need for a better nationwide continu-
ous registration of DSH and related socio-economic conditions. There is also a need for better mental health care management of DSH patients, and for experimental studies on the prevention of 4.15.2 deliberate self-harm: epidemiology and risk factors

SECTION 4  clinical syndromes of adult psychiatry 962
repetition. Although we know that persons who engage in DSH 
are at high risk for future fatal and non-fatal suicidal behaviour, development of effective intervention, and prevention programmes is a key priority.
Hawton, K. (ed.) (2005). Prevention and treatment of suicidal behaviour: 
from science to practice . Oxford University Press, Oxford.
De Leo, D., Bille-Brahe, U., Kerkhof, A., and Schmidtke, A. (eds.) (2004). 
Suicidal behaviour: theories and research ﬁ  ndings . Hogrefe and Huber, 
Göttingen, Germany.
Van Heeringen, K. (ed.) (2001). Understanding suicidal behaviour. 
The suicidal process approach to research, treatment and prevention .
John Wiley & Sons Ltd., Chichester, UK.
Hawton, K. and Van Heeringen, K. (eds.) (2000). The international 
handbook of suicide and attempted suicide . John Wiley & Sons, 
Chichester, UK.
Website of the International Association for Suicide Prevention (IASP):

Website of the International Association for Suicide Prevention (IASP): 
http://www.med.uio.no/iasp/
 1.  Morgan, H.G., Barton, J., Pottle, S., et al. (1976). Deliberate self-harm: 
a follow-up study of 279 patients. The British Journal of Psychiatry ,
128, 361–8.
 2. Kreitman, N., Philip, A.E., Greer, S., et al. (1969). Parasuicide. 
The British Journal of Psychiatry ,115, 746–7.
 3. Skegg, K. (2005). Self-harm. Lancet ,366, 1471–83.
 4. Platt, S., Bille-Brahe, U., Kerkhof, A., et al. (1992). Parasuicide in 
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4.15.3 Biological aspects 
of suicidal behaviour
Modelling suicidal behaviours

T o understand the biological underpinnings of multi-determined 
behaviours such as suicide and attempted suicide it is necessary to situate them within an explanatory model that can elaborate the causal pathways and interrelations between biological, clinical, genetic, and environmental factors that all play a role in suicidal behaviour. Where possible, such a model should be clinically explanatory, incorporate biological correlates, be testable in both clinical and biological studies, and have some utility in identifying high-risk individuals.
We have proposed a stress–diathesis model of suicidal behaviour 
wherein exposure to a stressor precipitates a suicidal act in those with the diathesis, or propensity, for suicidal behaviour.
(1) Stressors

(1) Stressors 
are generally state-dependent factors such as an episode of major depression or adverse life event. The diathesis, we have hypothe-sized, comprises trait characteristics such as impulsive aggression, and pessimism.
(1) Uncovering the biological mechanisms relevant 
to the stress and the diathesis dimensions of suicidal behaviour will facilitate the identiﬁ  cation of both enduring and proximal markers 
of risk, as well as potential targets for treatment.4.15.3 biological aspects of suicidal behaviour

SECTION 4  clinical syndromes of adult psychiatry 964
One biological correlate of the diathesis for suicidal behaviour 
appears to be low serotonergic activity. Abnormal serotonergic function may be the result of numerous factors including genetics, early life experience, chronic medical illness, alcoholism or sub-stance use disorder, many of which have been correlated with increased risk for suicidal behaviour. Moreover, serotonergic dys-function may underlie recurrent mood disorders or behavioural traits that characterize the diathesis, such as aggression and impul-sivity. In terms of stress response, the noradrenergic and HPA axis have been the focus of biological studies in suicidal behaviour. This chapter gives an overview of the major neurobiological ﬁ  ndings in 
suicide and attempted suicide, as well as emerging ﬁ  ndings from 
studies of genes related to those systems.
Serotonergic system

Serotonin is involved in brain development, behavioural regulation, modulation of sleep, mood, anxiety, cognition, and memory and is shown to be disturbed in various psychiatric disorders. Serotonergic function is under genetic control and, moreover, deﬁ  cits in function-
ing have been shown to be enduring , marking it as a biological trait. 
The serotonergic system became a target for investigation in rela-tion to suicide when, more than 30 years ago, Asberg and colleagues observed that depressed individuals who had either attempted suicide by violent means or subsequently died by suicide in the study follow-up period were more likely to have lower CSF 5-HIAA levels.
(2) Since that time the function of the serotonergic system

(2) Since that time the function of the serotonergic system 
in suicide and attempted has been examined in many paradigms, and while not all studies agree, there is substantial consensus that individuals who die by suicide, or make serious non-fatal suicide attempts, exhibit a deﬁ  ciency in CNS serotonin neurotransmission.
Evidence of hypofunction comes from cerebrospinal ﬂ  uid  and 
postmortem studies. 5-hydroxyindoleacetic acid (5-HIAA) is the major metabolite of serotonin and level of CSF 5-HIAA is a guide to serotonin activity in parts of the brain including the prefrontal cortex. There have been over 20 studies of CSF 5-HIAA and suicidal behaviour in mood disorders, and a meta-analysis of prospective studies of 5-HIAA found that in mood disorders lower CSF 5-HIAA increased the chance of death by suicide over fourfold over follow-up periods of 1–14 years.
(3)
Multiple postmortem studies  of suicide, report lower brainstem

(3)
Multiple postmortem studies  of suicide, report lower brainstem 
levels of 5-HIAA and serotonin (5-hydroxytryptamine, 5-HT) (see Mann et al. for a review
(4)). These deﬁ  cits in 5-HT or 5-HIAA are 
observable across diagnostic groups(5) and, despite early reports to 
the contrary, independent of suicide method. This abnormality appears to be largely speciﬁ  c to the brainstem, and multiple studies 
have reported no differences between suicides and controls in 5-HT level in other brain regions including the hippocampus, the occipital cortex, the frontal cortex, the temporal cortex, the caudate, the striatum, or the hypothalamus.
(4) Serotonin neurone 
cell bodies are in the brainstem raphe nuclei, while their axons innervate most of the brain including the ventral prefrontal cortex. Morphological analysis of stained serotonin neurones in the brain-stem of depressed suicides and non-suicides observed greater cell density in the dorsal raphe nucleus in the suicides

(6) suggesting that 
reduction in serotonin activity is associated with dysfunctional neurones and not with fewer neurones.
Neuroendocrine challenge studies  using fenﬂ  uramine provide 
further evidence of anomalous serotonergic function associated with suicidal behaviour. Fenﬂ  uramine is a serotonin-releasing 
drug and a reuptake inhibitor that may also directly stimulate postsynaptic 5-HT receptors. The release of serotonin by fenﬂ  uramine 
causes a measurable increase in serum prolactin levels that is an indirect index of central serotonergic responsiveness. In depressed patients, those with a history of suicide attempts have a more blunted prolactin response to fenﬂ  uramine challenge than non-
attempters with some evidence that the effect is more strongly related to seriousness of past attempt.
(7)
Studies of receptors  suggest lower serotonergic transmission in the

(7)
Studies of receptors  suggest lower serotonergic transmission in the 
central nervous system may be accompanied by a compensatory upregulation of some serotonergic postsynaptic receptors such as the 5-HT
1A and 5-HT2A, and a decrease in the number of serotonin 
reuptake sites.(4) There is a reported increase in the concentration of 
the postsynaptic 5-HT2A receptors in the prefrontal cortex of sui-
cides compared with non-suicides.(8) This increased binding is 
reﬂ ected in more protein and may be due to elevated gene expression in 
youth suicide.(9) Elevated 5-HT2A binding has also been reported in 
the amygdala in depressed suicides. In depressed and non-depressed suicides there is evidence that 5-HT
2A receptors are upregulated in 
the dorsal prefrontal cortex but not the rostral prefrontal cortex.(8)
Platelet studies  examine 5-HT2A in living subjects with respect to

Platelet studies  examine 5-HT2A in living subjects with respect to 
non-fatal suicide attempt. 5-HT2A receptors, serotonin reuptake 
sites, and serotonin second messenger systems are present in blood platelets, and changes in these platelet measurements may reﬂ  ect 
similar changes in the CNS. Multiple studies have reported higher platelet 5-HT
2A receptor numbers in suicide attempters compared 
with non-attempters and healthy controls.(11)
Studies of second messengers  indicate impaired 5-HT2A receptor 
mediated signal transduction in the prefrontal cortex of suicides, (12)
and in platelets 5-HT2A receptor responsivity is signiﬁ  cantly blunted 
in patients with major depression who have made high-lethality suicide attempts compared to depressed patients who have made low-lethality suicide attempts.
(13) The implications of such a defect

(13) The implications of such a defect 
in signal transduction, if present in the brain, would be that although there may be greater density of 5-HT
2A receptors, the signal trans-
duced by 5-HT2A receptor activation may be blunted, which would 
compound deﬁ  cient serotonergic input as seen in the lower levels of 
brainstem serotonin and/or 5-HIAA in suicide victims.
Some postmortem studies  of the postsynaptic 5-HT1A receptor 
report higher binding in prefrontal cortex and more rostral seg-ments of raphe nuclei, and lower binding in more caudal raphe nuclei, hippocampus, prefrontal cortex, and temporal cortex.
(7)
Less 5-HT1A autoreceptor gene expression is also reported in the dor-
sal raphe(14) and would favour higher serotonin neurone ﬁ  ring rates.
Postmortem studies of depressed suicides report fewer 5-HT

Postmortem studies of depressed suicides report fewer 5-HT 
transporters in prefrontal cortex, hypothalamus, occipital cortex, and brainstem.
(15) Moreover, in suicides this deﬁ  cit appears local-
ized to the ventromedial prefrontal cortex, whereas depressed indi-viduals who died of other causes had lower binding throughout the prefrontal cortex.
(16)
The emerging picture from postmortem studies of greater 
5-HT2A receptor binding in the frontal cortex of depressed indi-
viduals who die by suicide, fewer brainstem 5-HT1A autoreceptors, 
and fewer serotonin transporters in the cortex, as well as ﬁ  ndings of 
greater tryptophan hydroxylase (the rate-limiting step in serotonin synthesis) immunoreactivity in serotonin nuclei in the brainstem
(17)
all point to homeostatic changes designed to increase deﬁ  cient 
serotonergic transmission evidenced by low 5-HIAA in CSF and

965
brain, low 5-HT and 5-HIAA in brainstem, and blunted prolactin 
response to fenﬂ  uramine challenge.
Serotonergic dysfunction and suicide endophenotypes . Increased 
aggression has been associated with suicide and more highly lethal suicide attempts and impulsivity has shown a stronger relationship to non-fatal suicide attempts.
(18) Impulsive aggressive traits are 
potentially part of the diathesis for suicidal behaviour.(1) Reduced 
activity of the serotonin system has been implicated in impulsive violence and aggression in studies in a variety of paradigmsincluding: Low CSF 5-HIAA in individuals with a lifetime history of aggressive behaviour with personality and other psychiatricdisorders;
(19, 20) a blunted prolactin response to serotonin-releasing 
agent fenfluramine in personality disorder patients,(21, 22) and;
greater platelet 5-HT2A binding correlated with aggressive behav-
iour in personality and other psychiatric disorder patients.(23, 24)

In a postmortem study of aggression, suicidal behaviour, andserotonergic function a positive relationship between lifetimehistory of aggression scores and 5-HT
2A binding in several regions 
of prefrontal cortex of individuals who had died by suicide was found.
(25)
Positron emission tomography (PET) studies have shown a 
deﬁ cient response to serotonergic challenge in the orbitofrontal 
cortex, medial frontal, and cingulate regions in individuals with impulsive aggression compared to controls
(26, 27)  and lower sero-
tonin transporter binding in the anterior cingulate cortex in impul-sive aggressive individuals compared to healthy controls.
(28) The pre-
frontal cortex is important in the inhibitory control of behaviour, including impulsive and aggressive behaviour.
(29) Thus aggressive/

impulsive traits, related to serotonergic dysfunction, are potentially an aspect of the diathesis for suicidal behaviour, whereby aggressive/suicidal behaviours is manifested in response to stressful circum-stances or powerful emotions. This tendency might be conceived of as a diminution in natural inhibitory circuits, or as a volatile cogni-tive decision style.
Noradrenergic system
Within the stress–diathesis model of suicidal behaviour, it isthe confluence of stressful events with the diathesis that isthought to precipitate a suicidal act. Thus, investigating thefunctioning of stress response systems in suicidal individuals is important for elucidating neurobiological concomitants ofsuicidal behaviour and identifying targets for preventative inter-vention. The noradrenergic system and the HPA axis are two key stress response systems.

The majority of norepinephrine neurones in the brain are locat-
ed in the brainstem locus coeruleus. Postmortem studies of sui-cides have documented fewer noradrenergic neurones in the locus coeruleus.
(30) There are also indications of cortical noradrenergic 
overactivity including lower alpha and high-afﬁ  nity beta1-adrenergic 
receptor binding,(31) and lower β-adrenoceptor density and alpha2–
adrenergic binding in the prefrontal cortex in individuals who died by suicide.
(23) There is some, but not unanimous, evidence from 
prospective studies of lower levels of CSF 3-methoxy-4-hydrox-phenylglycol (MHPG), a metabolite of noradrenaline, in future suicides,
(33) although not in those making non-fatal suicide 
attempts.(34)
Fewer noradrenergic neurones observed in depressed suicides 
may indicate a lower functional reserve of the noradrenergic system, which if accompanied by an exaggerated stress response

may indicate a lower functional reserve of the noradrenergic system, which if accompanied by an exaggerated stress response 
with greater release of noradrenaline may result in norepinephrine depletion leading to depression and hopelessness, both of which are contributory factors to suicidal behaviour.
Noradrenergic and HPA axis responses to stress in adulthood 
appears to be greater in those reporting an abusive experience in childhood.
(35) Such individuals are potentially at greater risk in

(35) Such individuals are potentially at greater risk in 
adulthood for major depression and suicidal behaviour. Childhood abuse may be associated with increased risk for depression and sui-cidal behaviour because of a dysfunctional stress response both via the noradrenergic system and the HPA axis, and secondary effects of norepinephrine depletion and elevated cortisol levels. There is interaction between the noradrenergic system and the stress response activity of the HPA axis with reciprocal neural connec-tions between corticotropin-releasing hormone neurones in the hypothalamic paraventricular nucleus and noradrenergic neurones in human brainstem and the locus coeruleus.
(36)
The hypothalamic-pituitary-adrenal (HPA) 
axis
The hypothalamic-pituitary-adrenal axis is a major stress response

(36)
axis
The hypothalamic-pituitary-adrenal axis is a major stress response 
system. Major depression is associated with hyperactivity of the HPA axis,
(37) and suicidal patients in diagnostically heterogeneous 
populations exhibit HPA axis abnormalities, most commonly fail-ure to suppress cortisol normally after dexamethasone.
(33) We found 
most future suicides were dexamethasone suppression test (DST) non-suppressors.
(33) In mood disorders, DST non-suppressors
had a 4.5-fold greater risk of dying by suicide compared with suppressors.
(3) Moreover, non-suppression may be characteristic of 
more serious attempts that result in greater medical damage(38, 39)
or the use of violent method in the suicide attempt.(40) In other 
indices of HPA axis function suicide attempters had attenuated plasma cortisol responses to fenﬂ  uramine although that may indi-
cate less serotonin release and not an HPA abnormality,
(41, 42) and

(41, 42) and 
lower CSF corticotropin-releasing hormone (CRH) compared to non-attempters,
(43) though not all studies agree.
Larger pituitary and larger adrenal gland volumes are reported in 
depressed suicides,(44, 45) and fewer CRH-binding sites in the pre-
frontal cortex of depressed suicide victims which may mean recep-tor downregulation due to elevated CRF release.
(46)
As with the noradrenergic system, early life adversity appears to 
have lasting effects on stress response in the HPA axis in adulthood. Abnormalities in HPA axis function have been implicated in poor response to antidepressant treatment, and greater likelihood of relapse in major depression, both of which increase the risk for suicidal acts.
(33) Increased anxiety and agitation are another poten-

tial pathway whereby abnormal stress response, in both the norad-renergic and HPA axis, contributes to risk for suicidal behaviour.
Other biologic systems
Abnormality in the dopaminergic system has been reported in depressive disorders,
(47) however studies of dopaminergic function 
and suicidal behaviour are relatively few and inconclusive.(48) Low 
dihydroxyphenylacetic acid levels, indicative of reduced dopamine turnover, in the caudate, putamen, and nucleus accumbens are reported in depressed suicides,
(49) although the same group of inves-
tigators found no difference in number or afﬁ  nity of the dopamine 4.15.3 biological aspects of suicidal behaviour

SECTION 4  clinical syndromes of adult psychiatry 966
transporters.(50) Accordingly, it is unlikely that the reduced dopa-
mine turnover initially observe d in depressed suicides is a result
of decreased dopaminergic innervation of those regions. Prospective studies disagree as to whether CSF HV A predicts suicidal behaviour.
(51–53)
There is a well-documented relationship between thyroid 
dysfunction and depression(54) and some studies link thyroid
function and suicide. Abnormal thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) hasbeen observed in individuals who died by suicide in a follow-up study. 
(55)Abnormal TSH response to challenge tests has also been 
associated with poor response to antidepressant treatment anda higher relapse rate, which may increase risk for suicidalbehaviour.
(56)
Neurotrophins are involved in brain development and growth,

(56)
Neurotrophins are involved in brain development and growth, 
neuronal functioning, and synaptic plasticity. Lower protein levels and gene expression of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus,
(57, 58) and less mRNA of 
nerve growth factor, neurotrophin 3 and neurotrophin 4/5 in the hippocampus
(59) are reported postmortem in suicides. Lower plas-
ma BDNF has been reported in MDD suicide attempters compared to MDD non-attempters and healthy controls.
(60)
Suicide is more common in groups with very low cholesterol 
levels or after cholesterol lowering by diet (see(61) for a review). 
This relationship between cholesterol and suicide may be mediated by serotonergic function, as studies of non-human primates on a low-fat diet found lower serotonergic activity and increased aggressive behaviours.

(62) Long chain polyunsaturated fatty acids, particularly 
omega-3, may also be a mediating factor in the relationship between low cholesterol and increased risk for depression and suicide.
(63)
Lower docosahexaenoic acid percentage of total plasma polyun-saturated fatty acids and a higher omega-6/omega-3 ratio predicted depressed individuals who made a suicide attempt during a 2-year follow-up,
(64) and lower eicosapentaenoic acid is found in red 
blood cells of suicide attempters compared to controls.(65)
Neurobiology, genetics, and 
suicidal behaviour
Family, twin, and adoption studies support a genetic contribution 
to suicidal behaviour independent of psychiatric disorder (see Brent and Mann for a review),
(66) and genetic studies have sought

(66) and genetic studies have sought 
to determine the responsible genes for suicide and suicide attempt though linkage and SNP association studies. Candidate genes for most studies were selected based on evidence from neurobiological studies in suicide, as a result of which the serotonergic system has been most extensively investigated. A tri-allelic polymorphism in the serotonin transporter promotor has two alleles with lower transcriptional activity and fewer transporters. In varied psychiatric populations, despite some negative findings, the S, or more common lower-expressing allele, has been associated with suicide and with suicide attempts, particularly violent or high-lethality attempts.
(67) Functional MRI studies ﬁ  nd greater amygdala activa-

tion in individuals with the SS genotype when they are exposed to negative stimuli such as angry or fearful faces, negative words, or aversive pictures (see Brown and Hariri 2006 for a review).
(68) The 
amygdala is densely innervated by serotonergic neurones and 5-HT receptors are abundant, and plays a central role in emotionalregulation and memory. Excessive responses to emotionally nega-
tive events such as abuse, may be over-encoded and contribute to stress-sensitivity in adulthood and thereby to major depression after stress and even suicidal behaviour.
Other genetic studies of the serotonergic system including the 
5-HT
1A, 5-HT2A, 5-HT1B and other serotonin receptors have largely 
reported negative results, although there have been some positive ﬁ ndings for the 5-HT
2A 102C allele and attempted suicide or sui-
cidal ideation.(67) For tryptophan hydroxylase (TPH1 and TPH2

cidal ideation.(67) For tryptophan hydroxylase (TPH1 and TPH2 
are two forms of TPH with TPH1 only expressed in the brain dur-ing development), associations are reported with suicide and sui-cide attempt and TPH1 SNPs, however multiple negative ﬁ  ndings 
have also been reported,
(67) while haplotype and SNP studies sug-
gest the involvement of the TPH2 gene in suicide and suicide attempt, however again not all studies agree.
(67) Monoamine oxi-
dase (MAO-A) plays a key role in metabolism of amines. Low MAO activity results in elevated levels of serotonin, norepinephrine, and dopamine in the brain. The MAO-A gene has functional variable number tandem repeat however no association has been found between this uVNTR and suicidal behaviour, although there is some indication that it may be related to aggression
(67) and it is

(67) and it is 
linked to the impact of adversity in childhood on adult antisocial behaviour and trait impulsiveness.
(69, 70)
Genetic studies in dopaminergic system, noradrenergic system, 
BDNF, and GABA are few and generally negative,(67) although 
there are reports of positive association of the catechol- O-methyl-
transferase (COMT), a major catecholamine-catabolic enzyme, gene in Finnish and Caucasian suicide attempters
(71) and in Japanese 
suicides.(72) Inconsistent ﬁ  ndings in genetic studies of suicidal 
behaviour may be due to the complexity of the suicide phenotype, gene–gene interactions, the presence of multiple psychiatric disor-ders, population racial differences, possible epigenetic effects, and the inﬂ  uence of gene/environment interactions. Nonetheless, new

microarray technologies that test expression of thousands of genes simultaneously allowing better gene coverage, and haplotype map-ping approaches offer promise for future investigation. Other options include examining more basic endophenotypes such as mood regulation and decision-making.
Genes and environment
Early life stress in conjunction with genetic vulnerability can have enduring effects into adulthood and affect psychopathology and the functioning of biological systems including the serotonergic and stress-response systems (see Mann and Currier 2006).
(73) For 
example monkeys exposed to maternal deprivation in infancy and having the 5-HTTLPR lower expressing S allele in the serotonin transporter gene manifest a lowering of CSF 5-HIAA that persists into adulthood.
(74) In 6-month-old macaque monkeys exposed to

(74) In 6-month-old macaque monkeys exposed to 
social stress, those with the S allele had a higher ACTH response, an HPA axis hormone related to stress response, compared with those without that allele and to S allele animals who were maternally reared.
(75) Thus the low-expressing S allele not only increased vul-
nerability to stress in development, but early life stress may further interact with genotype to lower serotonergic function and to increase sensitivity to stressful events later in life, both of which are risk factors for suicidal behaviour.
In human studies, individuals who had experienced childhood 
maltreatment, those with the low-expressing S allele were at risk for

967
suicidal ideation and suicide attempt,(76) and those with a lower 
expressing variant of the MAO-A gene were more likely to manifest antisocial behaviour and more impulsivity as adults.
(69, 70)
There is much still to be learned about the biologic aetiology of suicidal behaviour and the pathways and mechanisms through which biologic dysfunction is involved in suicidal acts. New techniques for imaging the brain, identiﬁ  cation of basic intermedi-
ate phenotypes and denser gene markers will contribute to elucidating the biological factors and mechanisms involved in suicide and attempted suicide, and identifying potential targets for prevention .
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4.15.4 Treatment of suicide 
attempters and prevention of suicide and attempted suicide
In considering the treatment and prevention of suicidal behaviour 
account should be taken of recent trends in suicide and attempted suicide, particularly in individual countries. These have been reviewed in other chapters in this section. The term ‘attempted suicide’ is used in this chapter and includes any act of non-fatal self-poisoning or self-injury, irrespective of motive or intention.
Suicide prevention has been incorporated within the World 
Health Organization Health for All strategy
(1) and has received 
substantial support from the United Nations.(2) Furthermore, in

substantial support from the United Nations.(2) Furthermore, in 
recent years several countries have developed national suicide 
prevention programmes. Increased suicide rates in young people 
have probably acted as a stimulus behind this trend. However, 
suicide rates in most countries remain higher in older populations 
and prevention programmes must include this increasingly larger 
sector of society.Treatment of suicide attempters
Suicide attempts occur for a wide range of reasons. In many cases the primary aim is not death but some other outcome, such as demonstrating distress to other people, seeking a change in other people’s behaviour or temporary escape.
(3) This means that a broad 
range of treatments are required since the needs of individual patients will vary widely (Table 4.15.4.1).
Factors relevant to treatment needs in 
suicide attempts

(a) Repetition of attempts and risk of suicide
Repetition of attempts is common, with 15 to 25 per cent repeating 
suicidal acts within a year, and is associated with a greater risk of eventual suicide.
(4) The frequency of suicide following attempted 
suicide varies from country to country,(5) depending on the overall 
characteristics of the patient population and the rate of suicide in the general population. Prevention of repetition of suicidal behaviour and especially of suicide is a major aim in treating suicide attempters.
(b) Psychiatric and personality disorders
A range of psychiatric disorders are found in suicide attempters.(6)

Depression and alcohol abuse are particularly common. In addition, substantial proportions of patients have personality disorders. While treatment directed at the underlying causes of such disorders, where possible, will be important in managing attempted suicide patients, often the disorders themselves will require speciﬁ  c treatment.
(c) Life events and difﬁ  culties
Certain problems are particularly common in suicide attempters, 
including difﬁ  culties in interpersonal relationships, especially with 
partners and with other family members, employment problems, particularly in males, and financial difficulties. Life events, especially disruption in a relationship with a partner, frequently precede suicidal acts.
(7)
(d) Poor problem-solving skills
Many suicide attempters have difﬁ  culties in problem-solving, par-

(7)
ticularly in dealing with difﬁ  culties in interpersonal relationships.(8)
These difﬁ  culties are more marked in suicide attempters than in 
patients with psychiatric disorders who have not carried out a suicidal act.
Table 4.15.4.1  Factors relevant to treatment needs in suicide 
attempters
Risk of repetition of attempts
Risk of suicide
Psychiatric disorder (especially depression and substance abuse)
Personality disordersLife events and difﬁ  culties
Poor problem-solving skills
Impulsivity and aggression
Hopelessness
Low self-esteemMotivational problems and poor compliance with treatment4.15.4 treatment of suicide attempters and prevention of suicide and attempted suicide

SECTION 4  clinical syndromes of adult psychiatry 970
(e) Impulsivity and aggression
There is a strong link between suicidal behaviour and both impul-
sivity and aggression. There is also accumulating evidence that hypofunction of brain serotonergic systems is linked to aggression (and possibly impulsivity) and also to suicidal behaviour
(9) (see 
Chapter 4.15.3). It is unclear whether this represents a state phenomenon associated with psychiatric disturbance or a trait phenomenon, but current evidence points towards the latter.
(f) Hopelessness and low self-esteem
Hopelessness, or pessimism about the future, which has been shown to be a key factor linking depression with suicidal acts, is an important predictor of repetition of suicidal behaviour, and a risk factor for eventual suicide.
(10) Low self-esteem is another

(10) Low self-esteem is another 
important characteristic associated with suicidal behaviour. There is likely to be a link between low self-esteem and a tendency to experience hopelessness when faced by adverse circumstances.
(g)  Motivational problems and poor compliance with 
treatment
Management of suicide attempters is complicated by the fact that 
some patients appear to be poorly motivated to engage in aftercare. This is also likely to affect compliance with treatments. The style of organization of general hospital psychiatric services (including continuity of care) and the attitudes of clinical staff may be impor-tant factors determining whether patients engage in aftercare.
General overview of treatments

Treatments for suicide attempters include both psychosocial and pharmacological approaches. While these are considered separately below, in some patients both will be appropriate. This might be the case, for example, if a patient suffers from depression with biologi-cal features in the setting of employment and ﬁ  nancial difﬁ  culties, 
when treatment with an antidepressant might be combined with problem-solving therapy.
Psychosocial treatments
A range of psychosocial therapies have been evaluated in suicide attempters in randomized controlled clinical trials. The efﬁ  cacy of 
these approaches has been examined in a systematic review of the worldwide literature.
(11) The ﬁ  ndings from this review and some 
further studies are summarized below.
(a) Problem-solving

Meta-analysis of the results of trials that have been conducted so far to evaluate the effectiveness of brief problem-solving therapy (see Chapter 6.3.1) compared with treatment as usual indicates a trend towards reduction of repetition of self-harm episodes, but the total numbers of subjects and trials have precluded a deﬁ  nitive 
result. However, evidence of other positive outcomes, such as reduced levels of depression and hopelessness and improvement in problems, has been convincingly demonstrated in these studies.
(12)
This approach is useful, either used alone or in the context of other treatment. It is reasonably easily taught and can be used by clinicians from different professional backgrounds.
(b) Psychotherapy

Cognitive behaviour therapy, combined with care management has recently been shown to be effective in reducing frequency of suicide attempts and in producing other positive outcomes.
(13)A brief psychological intervention combined with provision of a treatment manual seems to be less effective in the treatment of patients with repeated attempts.
(14)
Two trials have been conducted in which an intensive form
of psychological treatment known as dialectical behaviourtherapy was evaluated.
(15,16) Female patients with borderline
personality disorders who had a history of repeated self-harmwere offered a year of individual and group cognitive behavioural therapy aimed at addressing the patients’ problems of motivation and strengthening their behavioural skills, particularly in relation to interpersonal difﬁ  culties. Compared with routine care this

approach seems to result in a reduction in repetition of self-harm as well as a number of other positive outcomes. Further evaluation of this approach is required to determine if it is effective inmale patients and in adolescents, and whether it can be delivered in an abbreviated form. While it is a labour-intensive approach, it appears to be helpful for what is a particularly difﬁ  cult group of 
patients.
(c) Outreach
Several trials have been conducted to assess the impact of community outreach, either for all patients or for those that have not attended treatment sessions. Some of these studies have included relatively intensive treatment programmes. Overall these studies indicate that some form of outreach may improve outcome in terms of reducing repetition of attempted suicide. In one study, nurse home visits to encourage non-attending participants to attend outpatient appointments resulted in a signiﬁ  cantly greater number of appoint-

ments attended as compared to the control group and there was a near signiﬁ  cant reduction in the rate of repetition of suicide 
attempts during the year after study entry.
(17) In other studies, 
telephone contact,(18) and contacting patients regularly by post(19)
have also produced promising results. Outreach combined with speciﬁ  c treatment may be useful, perhaps reserved for those who 
are poorly compliant with aftercare.
(d) Provision of emergency cards
In the United Kingdom there has recently been interest inproviding suicide attempters with cards which indicate howthey might get emergency help at times of crisis. Two initial,relatively small, studies of this approach, one involving adultsand the other young adolescents, produced encouraging results but a larger evaluation did not show the cards to be effective.
(20)

(20)
Provision of emergency cards requires there to be a 24 h service to deal with emergency calls. They might be thought helpful in a minority of cases, but there needs to be careful selection of patients who are offered this facility because of risk of it possibly being abused.
There have been relatively few treatment trials evaluating the effectiveness of pharmacological agents in suicide attempters. This perhaps reﬂ  ects the problems of compliance with therapy, which 
were noted earlier, and risk of overdose.
(a) Antidepressants
A trial in the Netherlands in which paroxetine was compared with placebo in patients who were all repeaters of self-harm but who did not suffer from current depressive disorder showed apparent beneﬁ  ts for a subgroup of patients who received paroxetine, namely

971
those who had a history of between one and four episodes of self-
harm. Patients with a history of ﬁ  ve or more episodes did not seem 
to beneﬁ  t.(21) The ﬁ  ndings of this study are clearly of interest 
(although post hoc  subgroup analyses of this kind must be treated 
with caution). Recently there has been much attention to the risk of antidepressants increasing suicidal ideation and acts in adolescents.
(22) Also, it has become clear that there is increased risk 
with all types of antidepressants during the initial period of treat-ment.
(23) These ﬁ  ndings have highlighted the need to be cautious 
in the use of antidepressants, to provide early follow-up after initiating therapy, and to consider combining antidepressant treat-ment with other therapies, especially for adolescents (in whom only ﬂ  uoxetine is currently recommended for the treatment of 
depression).
(b) Neuroleptics
A trial in which the depot neuroleptic ﬂ  upenthixol was adminis-

tered monthly in a dose of 20 mg for 6 months to repeaters of self-harm and compared with placebo in similar patientsappeared to show that the active drug was effective in reducingthe recurrence of self-harm.
(24) While this type of study requires 
replication, perhaps using one of the atypical oral neuroleptics in patients who frequently repeat self-harm may be worth trying.
(c) Lithium
A systematic review of trials of lithium therapy versus a range of other drugs and placebo in patients with affective disorders has shown convincing evidence that lithium may prevent suicide.
(25)
It is not known if it may be anti-suicidal in other groups of patients.
Management in clinical practice

(25)
Before a treatment plan can be formulated a careful assessment must be carried out. In conducting the assessment the clinician needs to try and establish good rapport with the patient and be sensitive to the patient’s preferences. The key factors that should be covered during the assessment are listed in Table 4.15.4.2. For the purpose of formulating a management plan it is particularly useful to draw up a problem list which summarizes the patient’s current difﬁ culties. This should be done in active collaboration with the 
patient as far as possible. Qualitative studies have shown that patients appreciate clinicians and other staff keeping them well informed of their mental and physical status and including them in decision-making in regard to their care.
(26)

(26)
During the assessment it is crucial to estimate the risk of suicide or another non-fatal attempt. However, accurate assessment is far from easy. Risk factors for suicide following attempted suicideare shown in Table 4.15.4.3. Because suicide is uncommon, thepredictive value of the items is limited. One predictor of suicide risk is the degree of suicidal intent involved in the current attempt (see Table 4.15.4.4). Clinicians should consider the use of the valu-able Beck Suicide Intent scale.
(27) Factors known to be associated 
with risk of a further attempt are listed in Table 4.15.4.5. It should be noted that while individuals who score positive on several of these factors will have considerably increased risk of repetition, a substantial proportion of those who repeat will not show these characteristics, i.e. the predictive value of scales to predict repeti-tion is modest.Table 4.15.4.2  The assessment of attempted-suicide patients
Factors that should be covered

Life events that preceded the attempt
Motives for the act, including suicidal intent and other reasons
Problems faced by the patient
Psychiatric disorder
Personality traits and disorderAlcohol and drug misuse
Family and personal history
Current circumstances Social (e.g. extent of social relationships)
 Domestic (e.g. living alone or with others)
 Occupation (e.g. whether employed)Psychiatric history, including previous suicide attempts
Assessments that should be made
Risk of a further attempt
Coping resources and supportsWhat treatment is appropriate to the patient’s needs
Motivation of patient (and signiﬁ  cant others where appropriate, to engage 
 in treatment)
Table 4.15.4.3  Factors associated with risk of suicide after 
attempted suicide
Older age
Male gender
Unemployed or retired
Separated, divorced or widowedLiving alone

Older age
Psychiatric disorder (particularly depression, alcoholism, schizophrenia, and  ‘sociopathic’ personality disorder)
High suicidal intent in current episode
Violent method involved in current attempt (e.g. attempted hanging, 
 shooting, jumping)
Leaving a notePrevious attempt(s) (including repetitive self-injury)
Table 4.15.4.4  Factors that suggest high suicidal intent
Act carried out in isolation
Act timed so that intervention unlikely
Precautions taken to avoid discovery
Preparations made in anticipation of death (e.g. making will, organizing  insurance)
Preparations made for the act (e.g. purchasing means, saving up tablets)
Communicating intent to others beforehandExtensive premeditation
Leaving a note
Note alerting potential helpers after the act

Subsequent admission of suicidal intent4.15.4 treatment of suicide attempters and prevention of suicide and attempted suicide

SECTION 4  clinical syndromes of adult psychiatry 972
(b) Treatment
The treatment plan should be drawn up on the basis of the patient’s 
needs and risks. Inpatient psychiatric treatment will usually be indicated for patients with severe psychiatric disorders, especially where immediate risk of suicide appears to be high.
(i) Psychiatric disorders
Major psychiatric disorders should be treated in the usual way, but with particular care about use of medication which might be toxic in overdose. Speciﬁ  c treatment should be provided for alcohol 
and drug abuse; indeed, a suicide attempt is sometimes the ﬁ  rst 
occasion that abuse may come to clinical attention.
(ii) Community therapy

Most patients can be managed in the community. Brief psychologicaltherapy, with a focus on problem-solving will be appropriatefor those patients who have clear problems, such as in interper-sonal relationships, employment, or social adjustment. Someform of outreach (e.g. home visiting, telephone contact) may be helpful to increase the proportion of patients who engage intreatment, but is not necessary for most patients. Outreach maybe essential in the treatment of patients in remote rural areas in developing countries.
If possible there should be continuity of therapy in terms of the 
same person who saw the patient in hospital after their attempt providing aftercare as this is likely to result in better compliance with therapy. Longer term cognitive behavioural therapy or dynamic psychotherapy may be required for patients whose attempts are

related to traumas, such as sexual abuse, or to personality disorder. 
People who are repeaters of suicide attempts may also require more intensive treatment, especially those who frequently repeat. If resources permit, the use of a programme based on dialectical behaviour therapy, possibly using a group format for at least part of treatment, might be considered.
(iii) Adolescents
Family therapy may be required for young adolescents, and also for patients with difﬁ  culties in relation to children. Group therapy may 
be helpful for adolescents who are repeaters of self-harm.
(28)
Prevention of suicide and attempted suicide
A widely diverse group of individuals are at risk of suicidal behav iour
and it occurs in relation to a wide range of problems and situations. For example, suicide may occur in the context of long-termdifﬁ culties extending back to childhood, acute severe life events or,

and it occurs in relation to a wide range of problems and situations. For example, suicide may occur in the context of long-termdifﬁ culties extending back to childhood, acute severe life events or, 
and perhaps most importantly, acute or long-term and relapsing mental illness. Because of this the range of potential prevention strategies is also considerable.
Suicide prevention programmes have been established in many 
countries. This is to be welcomed, not only because of the potential beneﬁ  ts in terms of suicide prevention, but also because of the 
likely beneﬁ  ts for the broader population of individuals with men-

tal health problems. When considering prevention strategies, it is important to be aware of and sensitive towards issues relating to culture and ethnicity. For example, while suicide rates are generally relatively low in young females in the United Kingdom, this is not the case in young Asian females of the Hindu faith, in which rates appear to be relatively high and greater than those of their male peers.
(29) The issues surrounding such deaths are often related to 
cultural clashes regarding values and expectations between young Asian females and their parents.
While ethical issues in relation to suicide prevention are not 
dealt with in detail in this chapter, they are none the less highly important.
(30) Opinions will vary, for example, about whether 
suicide should always be prevented. This particularly relates to suicides occurring in the context of terminal and/or painful physical

suicide should always be prevented. This particularly relates to suicides occurring in the context of terminal and/or painful physical 
illnesses, and relapsing and debilitating mental illnesses. The ethics of suicide prevention overlap those of assisted suicide and euthana sia. 
Psychiatrists are increasingly likely to be drawn into debate and controversy about the ethical aspects of these issues, particularly in relation to severe and chronic mental illness, and mental health aspects of assisted suicide and euthanasia in people with severe physical illnesses.
General principles of prevention
Broadly there are two approaches to suicide prevention.(31,32)
As described by Rose(33) in the context of prevention of health 
problems in general, one can distinguish between population approaches, which aim to decrease risk in the population as a whole, and high-risk group strategies, in which speciﬁ  c groups that

problems in general, one can distinguish between population approaches, which aim to decrease risk in the population as a whole, and high-risk group strategies, in which speciﬁ  c groups that 
are at increased risk are targeted. High-risk group strategies often appear more attractive and realistic. However, risk factors for many disorders are widely spread in the population and so the high-risk strategy tends to exclude a large number of people at moderate risk and is often ineffective in reducing the burden of a disease at the population level. Conversely, population strategies may appear more difﬁ  cult to achieve but are more likely to be effective in reduc-
ing population levels of disease (see also Chapter 7.4). The main population and high-risk group strategies in the prevention of suicide and attempted suicide which are considered here are shown 
in Table 4.15.4.6.
It is unclear if national suicide prevention programmes are

It is unclear if national suicide prevention programmes are 
effective, although evidence of effectiveness for speciﬁ  c components 
of such strategies is emerging.
(34) The most impressive programme, 
developed in Finland, was based on information from a detailed national study of all suicides in 1 year and includes a wide range of elements.
(35) A decline in the Finnish suicide rate has been 
attributed to the programme.(36) In England a national suicide 
prevention strategy with a suicide target was introduced in 2002.(37)
Strategies have also been introduced in Scotland(38) and Ireland.(39)
While prevention strategies are difﬁ  cult to evaluate(40) there are 
indications that programmes for prevention of suicide on a national scale may be effective.Table 4.15.4.5  Factors associated with risk of repetition of 
Previous attempt(s)
Personality disorder
Alcohol or drug abuse
Previous psychiatric treatmentUnemployment

Lower socio-economic status
Criminal record
History of violence
Age 25–54 years
Single, divorced, or separated

973
Population strategies
(a) Reducing availability of means for suicide
This is the most widely discussed population strategy.(41) It is based 
on evidence that if the availability and/or danger of a popular method for suicide changes then this tends to have an impacton suicide rates. The general principles of prevention through reducing availability of means are, first, that many suicidalacts occur impulsively and therefore if a dangerous means isavailable this is more likely to result in death and, secondly, thatthe eventual suicide rate in survivors of serious attempts isremarkably low. Also the common adage that if people are intent on committing suicide they will ﬁ  nd a means is not necessarily
correct (see below).
(i) Coal gas
The most cited evidence for the effectiveness of this approach is the reduction in suicides in the United Kingdom which occurred in the 1960s and early 1970s when toxic coal gas supplies were gradually replaced with non-toxic North Sea gas.

(42) Prior to this time coal 
gas poisoning through people placing their head in a gas oven was the most common method of suicide in the United Kingdom. As North Sea gas was gradually introduced the suicide rate dropped steadily, eventually being reduced by approximately a third. It is estimated that as many as 6000 deaths may have been prevented by this change. The effect also illustrates the point that when one method of suicide is no longer available people do not automati-cally turn to another, or if they do it may be to one that is less likely to cause death. Thus, it was some years before the suicide rate rose again, this being related to an increase in deaths from poisoning with carbon monoxide from car exhausts. Another factor that may have been relevant to the decline in suicides was the reduction in prescribing of barbiturates, these being replaced by far less toxic 
benzodiazepines.
(ii) Carbon monoxide
Suicide by carbon monoxide poisoning from car exhausts has

Suicide by carbon monoxide poisoning from car exhausts has 
become less common because cars are now ﬁ  tted with catalytic 
converters. This has resulted in a decline in suicide rates in countries where this method of suicide had become more common, particu-larly in young males.
(43)(iii) Firearms
The widespread availability of guns in certain countries, particu-larly the United States, has been proposed as an important reason for their relatively high suicide rates. Guns are used in more than half of all suicides in the United States and their use for suicide correlates with the holding of gun licences in households.
(44)
Some controversy surrounds the question of whether restricting availability of guns leads to a reduction in suicide rates, but the weight of evidence seems to indicate that it does.
(45)
(iv) Antidepressants

(45)
Given the very strong link between suicide and depression, and the risk of death from overdose of some of the older antidepressants, there has been much debate about whether more extensive use of newer, less toxic antidepressants would prevent suicides. This is not a simple question, as some patients respond better to the older tri-cyclic antidepressants. Another consideration concerns the cost of the newer antidepressants compared with the older varieties. Also it is very important to remember that most people who are taking antidepressants do not kill themselves with their antidepressants but use other methods. This and the probable selective prescribing of SSRIs to people judged to be at risk may account for the ﬁ  nding 
that suicide rates were higher in patients taking ﬂ  uoxetine than 
patients taking other and in some cases more toxic antidepres sants.
(46)
Nevertheless, common sense dictates that patients known to be at

(46)
Nevertheless, common sense dictates that patients known to be at 
risk, and especially those with a history of suicidal behaviour, should be prescribed the less toxic preparations.
(v) Analgesics
In the United Kingdom and some other countries there has been particular concern about deaths from self-poisoning with paracetamol. Due to evidence that countries which have fewer tab-lets per pack seem to have a lower rate of mortality from paracetamol self-poisoning and because overdoses of paracetamol are often taken impulsively and involve household supplies, legislation was introduced in the United Kingdom in 1998 to reduce in the number of tablets of paracetamol (and aspirin) available per pack. This resulted in fewer overdoses, decreased cases of hepatotoxicity due to paracetamol toxicity, and a reduced number of deaths from both paracetamol and aspirin.
(47)
(vi) Safety measures

(47)
Much attention has been paid to improving safety at popular sites for suicide. This includes erecting suicide barriers on bridges, multi-storey car parks, and other sites. If environmental changes are made such that a popular suicide site becomes safer, this does not mean that people at risk automatically move to using another site. For example, erection of barriers on the Clifton Suspension Bridge in Bristol, a popular site for suicide, has resulted in far fewer deaths by jumping.
(48)
Clinicians involved in the development of suicide prevention

(48)
Clinicians involved in the development of suicide prevention 
strategies should look very carefully for local patterns which might provide clues about potentially effective measures for reducing access to methods. This could include, for example, ensuring that psychiatric inpatient units are free of hooks, pipes, and other objects or structures from which patients could hang themselves, and that all bed rails are collapsible (compulsory in the United Kingdom), secure fencing of railway lines or waterways close to psychiatric hospitals, and making local popular sites for suicide safer (e.g. suicide barriers on bridges). In addition, attention should Table 4.15.4.6  Examples of strategies for prevention of suicide and 
Reducing availability of means for suicide
Educating primary care physicians
Inﬂ  uencing media portrayal of suicide
Educating the public about mental illness and its treatmentEducational approaches in schools

Befriending agencies and telephone helplines
Addressing the economic factors associated with suicidal behaviour
High-risk strategies
Prevention of suicide in: Patients with psychiatric disorders
 The elderly
 Suicide attempters
 High-risk occupational groups
 Prisoners4.15.4 treatment of suicide attempters and prevention of suicide and attempted suicide

SECTION 4  clinical syndromes of adult psychiatry 974
be paid to common dangerous methods of self-poisoning. Speciﬁ  c 
strategies may be required depending on local patterns . For example, 
the high rates of suicide in rural areas of developing countries due to self-poisoning with pesticides might be reversed with safe-storage programmes.
(b) Education of primary care physicians
Much of the attention regarding improved detection of individuals at risk has concerned the detection and management of depression in general practice. This was stimulated by ﬁ  ndings that showed 
many people who died by suicide or who attempted suicide had seen their general practitioners shortly before these acts. Evidence that an intensive educational programme for general practitioners might be effective in inﬂ  uencing suicide rates comes from a study 
conducted on the Swedish island of Gotland.
(49) In the year follow-
ing this programme the suicide rate dropped signiﬁ  cantly, prescrib-

ing of antidepressants by general practitioners increased, referrals to psychiatry, especially for depression, decreased, the amount of time lost from work for depression decreased, as did psychiatric admissions. Unfortunately this effect was fairly short-lived in that suicide rates rose again in subsequent years, which the authors attributed to some of the general practitioners having left the island. They also suggested that such programmes need to be repeated.
(50) It is also important to note that the suicide rate only 
declined in females. The evidence in this study was based on relatively 
small numbers, at least with reference to suicide, although the 
effects on the management and outc ome of depression were perhaps 
more impressive.
While the Gotland study has generated a lot of debate about

While the Gotland study has generated a lot of debate about 
suicide prevention in primary care, detection of people most at risk in general practice is extremely difﬁ  cult because a large number of 
patients share risk factors and because suicide is a rare event. The most pragmatic view is that effective detection and treatment of depression (and other psychiatric disorders) in primary care are extremely important aims in their own rights and that they might also have beneﬁ  ts in terms of preventing some suicides.
Psychiatrists involved in designing suicide prevention strategies 
might ensure that there are effective local educational programmes for clinicians in primary care and other settings regarding detection and treatment of people with mental disorders.
(c) Inﬂ  uencing media portrayal of suicidal behaviour
Dramatic reporting and portrayal of suicidal behaviour by the

Dramatic reporting and portrayal of suicidal behaviour by the 
media can facilitate suicidal acts in other people. This has been shown in a wide range of studies of both newspaper and television reporting of suicides and fictional presentations of suicidal behaviours in ﬁ  lms and television dramas. The impact of media 
presentations appears to be greatest where the method used in the suicidal act is described in detail, where details of the deceased and/or the site of the act is provided, and for deaths by suicide of celeb-rities. The largest impact of media inﬂ  uence is on young people, 
although there is also inﬂ  uence on older people.
(51)
In each country, consideration should be paid to the develop-
ment of consensus statements about media policies in relation to reporting and portrayal of suicide,
(52) which could be produced by

(52) which could be produced by 
joint working parties including representatives of the press, clinical and voluntary agencies, and experts in the ﬁ  eld of suicidal behav-
iour. More difﬁ  cult is the potentially valuable task of encouraging a 
policy whereby the media can be used to portray effective coping strategies for people in distress. Such a strategy will need to encom-
pass local cultural factors. Psychiatrists and other professionals developing suicide prevention strategies might examine the prac-tices of their local media with regard to reporting of suicides and, if 
necessary, hold meetings with media producers to explain the 
dangers of dramatic and extensive reporting, and also to explore how the media might help in prevention.
Concern is growing about inﬂ  uences on suicidal behaviour

Concern is growing about inﬂ  uences on suicidal behaviour 
through the internet, especially web sites providing instructions on methods of suicide and chat rooms whereby individuals can instruct. Some sites seem to be intended to promote suicide, such as those which initiate meetings between suicidal individuals. Attempts can be made to regulate such sites, but this impossible for sites from other countries. Also, internet providers can be encour-aged to ensure that sites offering positive help appear before less desirable sites.
(d)  Education of the public about mental illness and 
its treatment
In view of the very strong link between suicide and mental illness,

In view of the very strong link between suicide and mental illness, 
effective treatment of psychiatric disorders must be a central theme in suicide prevention. However, detection of people with disorders will depend on the awareness that they and those around them have regarding the signs and symptoms of disorder, and their will-ingness to seek appropriate help.
(53) These important stages in 
receiving effective help will depend on the general public’s attitudes towards mental illness and knowledge of its nature and the feasibility 
of treatment. In several countries, programmes to encourage

of treatment. In several countries, programmes to encourage 
education of the public about psychiatric disorders (especially depression) and to tackle stigmatization of those who are ill have been established. At this stage, evidence is lacking as to whether or not they have been successful. Psychiatrists and their colleagues might consider similar campaigns where these are not already in place, although the method of delivery of messages (e.g. media presentations, leaﬂ  ets, workshops, articles) will clearly depend on 
local factors.
(e) Educational approaches in schools
There have been three broad approaches in trying to prevent suicide through school-based programmes.
(54) The ﬁ  rst of these includes

(54) The ﬁ  rst of these includes 
teaching about the facts of suicide. Worrying evidence from the United States that such a programme appeared to lead to a small increase in pupils’ ratings of the acceptability of suicide as an option compared with the ratings of pupils who did not receive the pro-gramme suggests that this is not a wise approach.
Suicidal behaviour in young people often appears to be related to 
depression, anxiety, low self-esteem, difﬁ  culties during upbringing 
(e.g. abuse, deprivation), life events (especially break-up of relation-ships, family problems, and bullying), and poor problem-solving skills.
(54) Also, troubled and suicidal young people most often seek

(54) Also, troubled and suicidal young people most often seek 
help from their peers. A second school-based strategy has been the development of educational programmes in schools about recog-nition of psychological distress in individuals and their peers, prob-lem-solving, and peer support. Given the early age at which sui-cidal behaviour begins, such programmes should probably be targeted at extremely young school children, with later sessions for adolescents.
A third approach is to screen adolescents with questionnaires to 
detect children and adolescents at risk of psychiatric disorder and

975
possible suicidal behaviour. Pupils that are so detected will then 
need referral to an appropriate agency for further assessment and possible treatment. While there is some evidence to support such an approach it is not without drawbacks. (Suicide in children and adolescents is considered further in Chapter 9.2.10).
For psychiatrists and others involved in developing local pre-
vention strategies it is important to recognize that school-based approaches to prevention represents is a highly sensitive area and one where the most effective (and least risky) approach is at pres-ent unclear. Another important aspect of suicidal behaviour in school pupils is the management of the aftermath of suicides and its impact on other pupils and how to tackle outbreaks of self-harm.
(54)
(f) Befriending agencies and telephone helplines

(54)
A very important component of suicide prevention policy in many countries is the support provided by largely volunteer staffed befriending agencies and especially telephone helplines. The best known of these is Samaritans. A key principle on which such services are based is that people in distress and at risk of suicide will beneﬁ  t from being able to discuss their problems with someone 
entirely confidentially. Recently, more assertive outreach programmes, in which volunteers meet up with distressed individ-uals such as in prisons and in remote areas, have been added to the traditional telephone service. In the United Kingdom and elsewhere counselling by e-mail and text messaging is being used extensively.
The effectiveness of these approaches is largely unknown. 
Conducting controlled trials to examine their efﬁ  cacy is very difﬁ  -
cult. Naturalistic studies have produced conﬂ  icting evidence about

cult. Naturalistic studies have produced conﬂ  icting evidence about 
the effectiveness of the Samaritans in the United Kingdom.
(55,56)
An examination of changes in suicide rates in areas with and with-out crisis intervention services in the United States suggested that suicide rates in young white females may have been reduced in areas where such services were developed.
(57) Given the large 
numbers of contacts made with Samaritans in the United Kingdom (nearly 5 million in 2005), it appears that the service is valued by people in distress.
Volunteer-run telephone helplines and similar services may 
beneﬁ  t greatly from the support and advice of local clinicians, 
who should regard them as a potentially valuable element in a local suicide prevention strategy.
Addressing the economic factors associated with 
The association between suicidal behaviour and unemployment

The association between suicidal behaviour and unemployment 
and poverty suggests that in order for suicide rates to change mark-edly these important socio-economic factors must be modiﬁ  ed. 
The big increase in suicide rates during the economic depression of the late 1920s and early 1930s and the statistical association between suicide risk and unemployment would support this. Clearly such factors are increasingly a reﬂ  ection of the global economic situa-
tion, but the strategies of individual governments, particularly in relation to the employment prospects for young people, may be inﬂ uential. The main role of psychiatrists may be in highlighting 
these factors. The considerable evidence that changes in the economic environment can exert a powerful inﬂ  uence on suicide 
rates indicates that governments with serious intentions to reduce suicide rates should address these issues.

(32)Strategies for high-risk groups
There are a wide range of possible prevention strategies which can be targeted at high-risk groups. Here are some of the more important examples of such groups and relevant strategies will be discussed.
(a) Patients with psychiatric disorders
(i) Risk identiﬁ  cation
One approach to preventing suicide in people with known psychi-atric disorders is to try and use recognized risk factors for suicide in each disorder to identify high-risk patients. The main psychiatric disorders in series of people who have died by suicide are depression (approximately two-thirds), severe alcohol abuse (approximately 15 per cent), and schizophrenia (5–10 per cent).
(58) The main 
suicide risk factors identiﬁ  ed in these three disorders include, for

suicide risk factors identiﬁ  ed in these three disorders include, for 
example, previous attempts, family history of suicidal behaviour, and living alone. Comorbidity of disorders (e.g. depression and alcohol abuse) and of personality and psychiatric disorders increases risk.
One difﬁ  culty in using a risk-identiﬁ  cation approach, however,
is that the risk factors identified from studies of groups ofindividuals who have died from suicide are often misleadingwhen applied to individual patients. Also when applying suchfactors a relatively large number of individuals will appear tobe at risk when they may not in fact be so. In clinical practiceit is important to be aware of patients who, because of theirindividual characteristics, are at long-term high risk. Clinicians must also be aware of acute situations which may temporarily 
increase the risk in patients, be they ones at long-term risk
or not.
The most pragmatic approach, therefore, is to ensure that proven

or not.
The most pragmatic approach, therefore, is to ensure that proven 
effective treatments for patients with these conditions are available and also to be particularly cautious at times of obvious high risk. There are particular periods of risk of suicide for patients with psychiatric disorders. One of these is during the ﬁ  rst few weeks 
after discharge from psychiatric hospital.
(59) This emphasizes the 
necessity for continuity of care at this critical time. Other risk times may be following the break-up of a relationship or other signiﬁ  cant 
loss, during periods of marked hopelessness, shortly after discharge from hospital, and following recent suicidal behaviour by another patient or someone else close to the individual.
(ii) Preventative strategies
Prevention of suicide in patients with psychiatric disorders must be a major element in any suicide prevention strategy.
(60) Important

(60) Important 
strategies in preventing suicide in patients with affective disorders include active treatment of individual episodes of illness, psycho-logical therapy to improve compliance with treatment and assisting individuals to manage their disorder, use of lithium and other mood stabilizers for patients with recurrent bipolar disorders, and use of long-term antidepressants in patients with frequent relapses of depressive disorders. Risk is often greatest during the early stages of a disorder.
(53)
The risk factors in schizophrenia indicate that risk tends to be 
highest between episodes of acute illness when patients may have insight and feel hopeless about their circumstances and prospects. Risk is related more to affective symptoms than core features of the disorders.

(61) Continuity of care is likely to be a particularly impor-
tant factor in preventing suicides in such patients at risk, with care 4.15.4 treatment of suicide attempters and prevention of suicide and attempted suicide

SECTION 4  clinical syndromes of adult psychiatry 976
being continued energetically during periods of remission. 
Community psychiatric nurses have a very important role with such patients. The use of the newer atypical neuroleptics may also be beneﬁ  cial.
(62)
Direct treatment of abuse is likely to be the best preventive strat-
egy for patients with substance abuse disorders, with care taken to manage episodes of depression. The particularly high risk in the weeks following a break-up of a relationship for patients with severe alcohol abuse
(63) again points to the need for continuity of 
support in the community.
The prevention of suicide in patients with comorbid disorders,

The prevention of suicide in patients with comorbid disorders, 
especially the combination of depression with alcohol abuse and/or personality disorder, is a challenging task, particularlyas compliance with treatment is often less good than in patients with single disorders. Effective prevention is likely to dependon close integration of care between different statutory careagencies.
Another important element in prevention in this population is 
education in suicide risk assessment and management procedures for clinical staff at all levels of seniority. These should be incorpo-rated in educational programmes for risk assessment in general.
(b) Elderly people

In planning suicide prevention in the elderly population, account must be taken of the relative immobility of many older people. In a region of Italy, introduction of a telephone service toprovide support and access to emergency help for elderly persons at risk has been associated with an encouraging decline in elderly suicides in the area.
(64) This might serve as a model for other
countries.
(c) Suicide attempters
In view of the clear association between non-fatal suicidal behav-iour and subsequent suicide, establishment of adequate services for suicide attempters, including the provision of careful assessments of patients in the general hospital and offering treatments for which at least some indicators of beneﬁ  t are available (see above), is an

important element in any national suicide prevention strategy. There is good evidence that well-trained, non-medical psychiatric staff can effectively carry out assessments and arrange aftercare. Models for ideal services exist, such as those published by the National Institute for Clinical Excellence
(65) in the United 
Kingdom.
(d) High-risk occupational groups
Certain occupational groups are known to be at relatively high risk of suicide. In the United Kingdom these include farmers, veteri-nary surgeons, dental practitioners, medical practitioners, pharma-cists, and female nurses. It is interesting to note that all these groups have relatively easy access to dangerous methods for suicide. Since prevention through detection of those most at risk encounters the usual difﬁ  culties of prevention of relatively rare behaviour using

rather crude risk factors, it is probably more important to have general strategies for improving care in individual groups. In doctors, for example, there are some particular difﬁ  culties about 
conﬁ  dentiality and therefore providing easy means of doctors 
getting conﬁ  dential help is important. In farmers, improving the 
knowledge and attitudes of farming communities towards psychi-atric disorder, and removing access to ﬁ  rearms at times of risk, are 
likely to be important.(e) Prisoners
There are relatively high suicide rates in prisoners,(66) especially 
young males held on remand. While one aspect of prevention is through ensuring that prisons and police cells are safe in terms of absence of structures from which inmates can hang themselves, 
there are a range of other potentially useful and humane strategies.

there are a range of other potentially useful and humane strategies. 
These include careful assessments of new inmates using risk-assessment procedures, training of staff with regard to both assess-ment skills and attitudes towards mental health problems andsuicide prevention, in-reach programmes by befriending organiza-tions such as the Samaritans, and ready access to psychiatric and psychological services. Clinicians involved in local suicide preven-tion programmes should include prisons in their considerations.
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4.16
Culture-related speciﬁ  c 
psychiatric syndromes
The concept of culture-related speciﬁ  c 
(psychiatric) syndromes
In certain ways, all psychiatric disorders are more or less inﬂ  u-
enced by cultural factors, in addition to biological and psycho-
logical factors, for their occurrence and manifestation. ‘Major’ psychiatric disorders (such as schizophrenia or bipolar disorders) 
are more determined by biological factors and relatively less
by psychological and cultural factors, but ‘minor’ psychiatric
disorders (such as anxiety disorders, conversion disorders, or 
adjustment disorders) are more subject to psychological causes as well as cultural factors. In addition to this, there are groups of 
psychiatric disorders that are heavily related to and inﬂ  uenced
by cultural factors, and therefore addressed as culture-relatedspeciﬁ  c psychiatric syndromes.
Culture-related speciﬁ  c psychiatric syndromes, also called culture-
bound syndromes

(1) or culture-specific disorders,(2) refer to 
mental conditions or psychiatric syndromes whose occurrence 
or manifestations are closely related to cultural factors and thus warrant understanding and management primarily from a cultural perspective. Because the presentation is usually unique, with spe-cial clinical manifestations, the disorder is called a culture-related speciﬁ  c psychiatric syndrome.
(3) From a phenomenological point 
of view, such a condition is not easily categorized according to 
existing psychiatric classiﬁ  cations, which are based on clinical 
experiences of commonly observed psychiatric disorders in western societies, without adequate orientation towards less 
frequently encountered psychiatric conditions and diverse cultures 
worldwide.

Around the turn of the twentieth century, during a period of 
colonization by western societies, western ministers, physicians, 
and others visited faraway countries, where they encountered 
behaviours and unique psychiatric conditions that they had never 
experienced at home. Most of these conditions were known to the local people by folk names, such as latah ,amok ,koro ,susto ,
and so on, and were described by westerners as exotic, rare, 
uncommon, extraordinary mental disorders, mental illnesses 
peculiar to certain cultures, or culture-bound syndromes. The latter term implies that such syndromes are bound to a particular 
cultural region.
(4)
Recently, however, cultural psychiatrists have realized that such

(4)
Recently, however, cultural psychiatrists have realized that such 
psychiatric manifestations are not necessarily conﬁ  ned to particular ethnic-cultural groups. For instance, epidemic occurrences of koro
(penis-shrinking panic) occur among Thai or Indian people, not only among the Southern Chinese as originally claimed; and spo-
radic occurrences of amok  attacks (mass, indiscriminate homicidal 
acts) are observed in the Philippines, Thailand, Papua New Guinea, 
and in epidemic proportions in many places in South Asia,
(5) in 
addition to Malaysia where it was believed to most commonly occur. T errifying examples of amok  have recently occurred with 
frequency on school campuses and in workplaces in the United 
States.
Therefore, the term culture-bound does not seem to apply, 
and it has been suggested that culture-related speciﬁ  c psychiat-
ric syndrome would be more accurate to describe a syndrome

States.
ric syndrome would be more accurate to describe a syndrome 
that is closely related  to certain cultural traits  or cultural
features  rather than bound  speciﬁ  cally to any one cultural system
orcultural region .
(4) Accordingly, the definition has been
modiﬁ  ed to a collection of signs and symptoms that are restrict-
ed to a limited number of cultures, primarily by reason of
certain of their psychosocial features,(6) even though it is recog-
nized that every psychopathology is inﬂ  uenced by culture to a 
certain degree.
Subgrouping of culture-related 
speciﬁ  c syndromes
In order to organize and categorize the various culture-related 
syndromes, several different subgroup systems have been proposed by different scholars in the past, such as by cardinal symptoms or 
by ‘taxon’ (according to a common factor). However, instead of

by ‘taxon’ (according to a common factor). However, instead of 
focusing on the clinical manifestation descriptively, it will be more meaningful to subgroup the syndromes according to how they might be affected by cultural factors.
It has been recognized that there are different ways culture 
contributes to psychopathology. Namely: pathogenetic effect  (culture 
has causative effect), pathoselective effect  (culture selects the nature 
and type of psychopathology), pathoplastic effect  (culture contrib-
utes to the manifestation of psychopathology), pathoelaborating 
effect  (culture elaborates and reinforces certain types of manifesta-
tions), pathofacilitating effect  (culture contributes to the frequent 
occurrence of particular psychopathologies), or pathoreactive effect
(culture determines the reaction to psychopathology). Furthermore,

(culture determines the reaction to psychopathology). Furthermore, 
culture impacts differently on different types of psychopathology.

SECTION 4  clinical syndromes of adult psychiatry 980
If the psychopathology is divided into that which is more biologically 
determined (such as organic mental disorders or major psychiatric 
disorders), psychologically determined (such as minor psychiatric 
disorders), or socio-culturally determined (such as culture-related 
speciﬁ  c syndromes or epidemic mental disorders), it can be said 
that a pathoreactive effect is observed for all types of psychiatric 
disorders while a psychogenetic effect is observed mainly for those 
psychiatric disorders which are more socio-culturally determined, 
such as culture-related speciﬁ  c syndromes or epidemic mental 
Academically identiﬁ  ed culture-related speciﬁ  c syndromes can 
be compared according to two parameters, namely, the different 
means of cultural impact and the speciﬁ  city of the manifestation. 
It will be useful to determine the basic ways culture contributes

It will be useful to determine the basic ways culture contributes 
to the psychopathology, namely: pathogenic, pathoselective, 
pathoplastic, pathoelaborating, pathofacilitating, or pathoreac-
tive effects; and to what extent the manifested syndrome is:
speciﬁ  c, mixed, or non-speciﬁ  c (Fig. 4.16.1). For example, the 
primary cultural contribution to koro  is a pathogenic effect
with specific manifestation; to latah  a pathoelaborating
effect with speciﬁ  c manifestation; and to susto  a pathoreactive 
effect with non-speciﬁ  c manifestation.Culture-related beliefs as causes of the occurrence 
(pathogenetic effects)
(a) Koro (genital-retraction anxiety disorder)
(i) Deﬁ  nition
Koro  is a Malay term which means the head of a turtle, symbolizing 
the male sexual organ which can ‘shrink’ . Clinically koro refers to

the male sexual organ which can ‘shrink’ . Clinically koro refers to 
the psychiatric condition in which the patient is morbidly con-
cerned that his penis is shrinking excessively and subsequently dan-
gerous consequences (such as death) might occur. The manifested 
symptoms may vary from simple excessive concern to obsessive/
hypochondriac concern, intense anxiety, or a panic condition relat-
ed to the shrinking of the penis. Clinically, this is usually a benign 
(non-psychotic) condition that occurs in individual, as a sporadic 
case, but occasionally it may grow to epidemic proportions, so that 
several hundreds or a thousand people may develop this disorder 
in a panic manner within a limited time of several weeks or several 
months. The majority of cases are young males who fear that their 
penises are shrinking. However, the organ concerned may be any

penises are shrinking. However, the organ concerned may be any 
protruding part of the body, such as the nose or ear (particularly 
when patients are prepuberty children) or the nipples or labia (in 
females).
Sporadic occurrences of female koro  cases have never been 
reported. However, in koro epidemics, a small portion of the victims 
may be female.(7,8) In those cases, the female patients demonstrate 
slightly different clinical pictures, mainly focusing on the retrac-
tion of the nipples and some on the labia. The clinical condition 
is characterized by a more or less hysterical panic, associated with 
multiple somatic symptoms, a bewitched feeling, or the misinter-
pretation or accusation by others of being bewitched.
(ii) Geographic and ethnic group distribution
Cultural psychiatrists originally considered koro  to be a culture-

bound disorder related only to the Chinese. Most Chinese investi-
gators have taken the view that the disorder is related to the Chinese 
cultural belief in suoyang , literally means shrinkage of yang organ 
due to excess loss of Y ang (male) element. It has been speculated 
further that the occurrence of koro among people in South Asian 
countries, such as Malaysia and Indonesia, was the result of Chinese 
migrants. However, this cultural-diffusion view is doubted now, 
since koro epidemics have been reported in Thailand and India as 
well, involving non-Chinese victims.
As a result of the dissemination of knowledge about koro as a 
culture-bound syndrome, there is increased literature reporting so-
called koro  cases from various ethnic groups around the world,

called koro  cases from various ethnic groups around the world, 
such as from the United Kingdom, Canada, and Israel. However, 
it was pointed out that among the cases reported, all suffered 
primarily from many psychiatric conditions: affective disorders, 
schizophrenia and anxiety disorders, drug abuse, or organic brain 
disorders. Therefore, they were referred as having koro-like symp-
toms, not exactly the same as the koro syndrome. It is necessary for 
clinicians to recognize that koro is referred to on different levels as: 
a symptom, a syndrome, or an epidemic disorder.
(iii) Epidemic of koro
Koro  attack may occur occasionally as endemic or epidemic, involv-
ing many victims. Epidemic koro has been observed in several areas: 
Guangdong area of China, Singapore, Thailand, and India. As an

Guangdong area of China, Singapore, Thailand, and India. As an 
epidemic, it is manifested as a panic state rather than an anxiety or 
obsessive state. The epidemic koro has tended to occur when there Fig. 4.16.1 Position of culture-related syndromes according to two parameters 
(This article was published in Handbook of Cultural Psychiatry, Tsend, W.S., 
copyright Elsevier (2001).)

981
was socio-political stress within the epidemic areas, and an outburst 
of koro by a group of people may be interpreted as a way to deal 
with the social stress that they encountered.
(iv) Diagnostic issue
Clinicians habitually try to ﬁ  t pathologies into certain diagnostic 
categories. Because the patient, based on his misinterpretation, is morbidly preoccupied with the idea that certain ill-effects may occur due to the excessive retraction of his genital organ, the condition may, in a broad sense, be classiﬁ  ed as a hypochondriacal 
disorder as deﬁ  ned in DSM-IV . The condition is also similar to a

disorder as deﬁ  ned in DSM-IV . The condition is also similar to a 
body dysmorphic disorder, as the patient is preoccupied with a cul-turally induced, imagined defect in his physical condition. If the focus is on how the patient reacts emotionally, how he responds to the culture-genic stress, with fear, anxiety, or a panic state, anxiety disorder may be considered. However, when we try to cat-egorize culture-related speciﬁ  c syndromes according to the existing 
nosologically oriented classiﬁ  cation system, their meaning and 
purpose are lost.
(v) Therapy
As for therapy of sporadic individual cases, assurance may be provided or medical knowledge offered in the form of educational counselling to eliminate the patient’s concern about impending death. This supportive therapy may work in many cases, but, for someone who ﬁ  rmly believes the koro concept, it may not. In gen-

eral, a young, unmarried male, who lacks adequate psychosexual knowledge and experience, will respond favourably to therapy. If necessary, it is desirable to work on issues such as the patient’s self-image, self-conﬁ  dence, or his masculinity.
(b) Dhat syndrome (semen-loss anxiety)
Very closely related to the genital-retraction anxiety disorder ( koro)
is the semen-loss or semen-leaking anxiety disorder, or spermator-rhea, also known by its Indian folk name, dhat  syndrome. The dhat
syndrome refers to the clinical condition in which the patient is morbidly preoccupied with the excessive loss of semen from an improper form of leaking, such as nocturnal emissions, masturba-tion, or urination. The underlying anxiety is based on the cultural belief that excessive semen loss will result in illness. Therefore, it is a pathogenically induced psychological disorder.
(9,10) The medical

(9,10) The medical 
term spermatorrhea is a misnomer, as there is no actual problem of sperm leakage from a urological point of view.
From a clinical point of view, the patients are predominantly 
young males who present vague, multiple somatic symptoms such as fatigue, weakness, anxiety, loss of appetite, and feelings of guilt (about having indulged in sexual acts such as masturbation or hav-ing sex with prostitutes). Some also complain of sexual dysfunction (impotence or premature ejaculation). The chief complaint is often that the urine is opaque, which is attributed to the presence of semen. The patient attributes the passing of semen in the urine to his excessive indulgence in masturbation or other socially deﬁ  ned 
sexual improprieties.
(11) The syndrome is also widespread in Nepal, 
Sri Lanka (where it is referred to as prameha  disease), Bangladesh, 
and Pakistan.
(c) Sorcery fear and voodoo death (magic-fear-induced death)

The peculiar phenomenon of voodoo death refers to the sudden occurrence of death associated with taboo-breaking or curse fear. It is based on the belief in witchcraft, the putative power to bring about misfortune, disability, and even death through spiritual 
mechanisms.
(12) A severe fear reaction may result from such beliefs, 
which may actually end in death. From a psychosomatic point of view, it would be psychogenically induced death. From a cultural psychiatric perspective, it is another example of culture-induced morbid fear reaction.
Medically it has been recognized that sudden death was related

Medically it has been recognized that sudden death was related 
to psychological stress occurring during experiences of acute grief, the threat of the loss of a close person, personal danger, or other stressful situations. It has been speculated that the cause of death was possibly from natural causes; the possible use of poisons due to sorcery or witchcraft; excessive fear reaction; or death from dehydration or existing physical illness due to old age.
Culture-patterned speciﬁ  c coping reactions 
(pathoselective effect)
(a) Amok (indiscriminate mass homicide attacks)
(i) The nature of the behaviour
Amok  is a Malay term that means to engage furiously in battle. 
Clinically amok  refer to an acute outburst of unrestrained violence 
associated with (indiscriminate) homicidal attacks, preceded by a period of brooding and ending with exhaustion and amnesia.
(13)
Amok  homicides are distinct from other murders: the killer chooses

(13)
Amok  homicides are distinct from other murders: the killer chooses 
an extremely destructive weapon, a crowded location, and insanely and indiscriminately kills a large number of people.
(14)
There has been much speculation as to why amok  behaviour 
tends to occur in Malay society. One explanation is its connection to the religious background of the people. Muslims are not permit-ted to commit suicide, which is considered a most heinous act in the Mohammedan religion. In the past, aggressive-homicidal behaviour inﬂ  uenced by infectious diseases has been considered, 
along with malaria, dengue, neurosyphilis, epilepsy, and so on, as biological in some cases. From a psychological point of view, an extraordinary sensitivity to hurt and the tendency to blame others for one’s own difﬁ  culties are considered possible causes for the

phenomenon. Loss of social standing, by way of insult, loss of employment, or ﬁ  nancial loss, has been posited as a precipitating 
event for amok .
(ii) Amok behaviour in other areas
The outburst of aggressive (mass) homicidal behaviour is not 
necessarily conﬁ  ned to one cultural area, but can potentially be 
observed elsewhere, such as the territory of Papua and New Guinea, or many areas in South Asia, such as Thailand, the Philippines, Lao, and Indonesia.
(5) It has challenged the previous view that amok
occurs endemically within a particular society. It has been indicated that amok  could happen in a fashion by communicability and 
through transmission from one population to another.
(5) During 
the past decade in the United States, there have been increasing epi-sodes of massive (and aimless) killing of people in neighbourhoods, workplaces, and of teachers/students in schools by deadly military weapons. These are American versions of amok  attacks.
(b) Family suicide

When adults encounter severe difﬁ  culties (such as ﬁ  nancial debt 
or a disgraceful event), there are many ways to deal with such problems. As one of the ways to cope with the difﬁ  cult situation, 
Japanese parents, may decide to commit suicide together with their young children. This stress-coping method is based on the cultural 4.16 culture-related specific psychiatric syndromes

SECTION 4  clinical syndromes of adult psychiatry 982
belief that it would be disgraceful to live after a shameful thing 
had happened, and that the shame would be relieved by ending one’s life. This is coupled with the belief that the children, if left as orphans (after parents’ committing husband–wife double sui-cide), would be mistreated by others. ‘Blood is thicker than water’ is the common saying reﬂ  ecting the emphasis of blood-related 
family tie. Therefore, it would be better for them to die with their parents. This unique way of solving problems was often observed in Japan in the past. It is declining now but still observed some times.
(c) Cargo-cult syndromes (millenniary delusions)

Numerous social and behaviour scientists have noted that, histori-cally, there have been occurrences of crisis cults in many different countries. The Taiping (Great Peace) Rebellion in China, Kikuyu maumau in Kenya, and the Ghost Dance of the Plains Indians of North America are some examples. Central to all these cultures are marked feelings of inferiority, conﬂ  ict, and anxiety among 
the member-participants after being exposed to other, superior cultures and an attempt to renovate their self-images. Underlying these non-logical, magic-religious endeavours is a strong wish for resolution of their social, economic, and political problems and for a new and better way of life, such as that of the invading, superior cultures.
One kind of crisis cult is the cargo cult that has repeatedly aris-
en in Melanesia over the past century as a means of obtaining the manufactured articles possessed by European invaders.
(15) Cargo

(15) Cargo 
is a neo-Melanesian or pidgin word that designates all of the manufactured goods, including canned foods and weapons, pos-sessed by the Europeans, which are greatly desired by the indige-nous people. Without knowing how the cargo was manufactured in the home countries of Europe, based on their own folk beliefs, the local people thought that it was given to the white people by their powerful ancestors through the performance of properrituals. Accordingly, the local people tried to perform the white people’s rituals, in the hopes that their ancestors would send them a lot of cargo and their lives would eventually be full of wealth. This behaviour might be individual, or it might involvea group of followers that gave up their normal lives to perform religious rituals, waiting for the arrival of the cargo, not only for

several months, but for many years. They would become collec-
tively deluded and led by a cult leader. As a culture-relatedspeciﬁ  c syndrome, it may be understood that culture contributed 
to the stress that was encountered and also shaped the unique, pathological pattern of coping with it, a combination of patho-genic and pathoselective effects.
Culture-shaped variations of psychopathology 
(pathoplastic effect)
This category includes a group of disorders that manifests a clinical 
picture that is considerably different from the ordinal symptom-atology of identiﬁ  ed disorders described in current psychiatric 
classiﬁ  cations (of Euro-American origin). It is considered that the

classiﬁ  cations (of Euro-American origin). It is considered that the 
uniqueness of the symptomatology may be culturally attributed, i.e. due to cultural pathoplastic effects. Culture affects not only the content of symptoms, but, even more, the total clinical picture by the absence, addition, or variation of symptoms, resulting in con-siderable change in the manifestations of variations or subtypes of universally recognized psychiatric disorders.(a) Anthropophobia (interpersonal relation phobia)
(i) Deﬁ  nition and nature of the disorder
Anthropophobia is the English translation for the Japanese term taijin-kyofu-shio . In Japanese, taijin  means interpersonal, kyofu
means phobic, and shio means syndrome or disorder. Therefore, 
taijin-kyofu-shio  literally means the disorder with fear of inter-
personal relation.
(16)Taijinkyofushio  is said to be prevalent among

(16)Taijinkyofushio  is said to be prevalent among 
Japanese and is considered a culture-related psychiatric disorder. According to the clinical study, the onset of illness was as early mostly between 15 and 25 years, more prevalent among males than female. The cardinal symptoms manifested by the patients are: fear of one’s bodily odours, fear of ﬂ  ushing, fear of showing odd atti-
tudes towards others, fear of eye contact with others, concern about others’ attitudes towards oneself, and fear of body dysmorphia.
(ii) Dynamic interpretation and culture formulation
The characteristic of taijinkyofushio  is that the fear is induced in the

The characteristic of taijinkyofushio  is that the fear is induced in the 
presence of classmates, colleagues, or friends, those who are neither particularly close (such as family members) nor totally strange (such as people in the street). In other words, subjects are concerned with how to relate to people of intermediate familiarity. It is towards these people that a person must exercise delicate social etiquette. This is different from social phobia described in western societies, where patients have fear of socializing with strangers.
Culturally it has been explained that Japan is a situation-oriented 
society, very much concerned with how others see one’s behaviour. It is considered that the act of staring at the person to whom one is talking is quite extraordinary and considered to be rude. Thus, there are cultural characteristics that cause Japanese to be hyper-sensitive about looking at and being looked at.

Taijinkyofushio  is a psychological disorder of the adolescent. 
It is closely related to the problems associated with psychological development in the area of socialization. The Japanese child is raised in an atmosphere of indulgence and trust. However, when this protected child enters the wider world of junior high school, he or she faces multiple tasks: coping with conﬂ  ict between biological 
needs and social restrictions, personal identity problems, and an increasing need for acceptance and love by others in social settings. This intensiﬁ  es a feeling of unworthiness, making him or her more 
concerned about others’ sensibilities and reactions.
(b) Brain fag syndrome

This syndrome was described originally as a very common minor psychiatric disorder occurring among the students of Southern Nigeria. Clinically, it is characterized by subjective complaints of intellectual impairment, (visual) sensory impairment, and somatic complaints, mostly of pain or a burning sensation in the head and neck. The student-patients often used the term brain fag to complain that they were no longer able to read, grasp what they were reading, or recall what they had just read, basically stressing their difﬁ  culty in mental function. Therefore, the term brain 
fag syndrome was suggested for this distinct clinical mental condition.
(17)
In Nigeria, education was often a family affair, in which one of 
the brighter children was supported ﬁ  nancially by family members;

(17)
the brighter children was supported ﬁ  nancially by family members; 
the educated member in turn was expected to be responsible for other family members when the need arose. Because of this family aspect of education, the student was burdened by the responsibility of maintaining the family’s prestige. Thus, his or her academic

983
success or failure was associated with great stress. Therefore, it can 
be said that this syndrome is adjustment disorder with somatic feature and its symptomatology is shaped by culture.
(c) Arctic hysteria (pibloktoq)
Arctic (or polar) hysteria, also known by the local name pibloktoq ,
refers to a unique hysterical attack observed among the polar Eskimo people living in Arctic areas. The clinical condition is characterized by the sudden onset of loss or disturbance of consciousness. During the attack, as the patient may showvarious abnormal behaviours, such as tearing off his or her clothing, glossolalia, fleeing (nude or clothed), rolling in the snow, throwing anything handy around, performing mimetic acts, convulsion, or other bizarre behaviour. This emotional outburst occurs predominantly in women, but occasionally among men.
(18)
No speciﬁ  c precipitating causes are noted. It has been speculated 
that the reaction is a manifestation of the basic Eskimo personality.

(18)
that the reaction is a manifestation of the basic Eskimo personality. 
Because the reaction is prevalent in winter, it is also thought that it may be related to increased threats of starvation or higher accident 
rates. Generally, it is suspected that the disorder is due to some basic, underlying anxiety, triggered by severe, culturally typical stresses: fear of certain impending situations, fear of loss, or fear of losing emotional support, including the sense of being on safe, solid, familiar ground.
(d) Malignant anxiety
A special, intensiﬁ  ed form of anxiety disorder, termed as malignant 
anxiety, was reported to occur in Africa.(19) The condition was

anxiety, was reported to occur in Africa.(19) The condition was 
characterized by intense anxiety, extreme irritability, restlessness, and intense fear, and, therefore, named it malignant anxiety. It was referred to as frenzied anxiety as well. Often, the patient claimed that there was a change in his sense of self and reality, but there was no sign of personality deterioration or disintegration and no latent or overt psychotic symptoms. However, patients often suffered from intense feelings of anger that led to homicidal behaviour. The condition usually occurred in sporadic cases, but occasionally as an endemic. The disorder was thought to be situation related, associ-ated with problems of adaptation to new and stressful life situa-tions. Very often the patients were culturally marginal persons, who were in the process of renouncing their age-old cultures, but had failed to assimilate the new.

Culturally elaborated unique behaviour 
(pathoelaborating effect)
(a) Latah (startle-induced dissociative reaction)
(i) Deﬁ  ning the condition
Latah  is a Malay word referring to the condition in which a person, 
after being startled by external stimuli, such as being tickled, suddenly experiences an altered consciousness and falls into a transient, dissociated state, exhibiting unusual behaviour (such as echolalia, echopraxia, or command automatism), including explo-sive verbal outbursts, usually of erotic words that are not ordinarily acceptable.
(20) Beside Malaysia, the phenomenon has been observed 
in other places around the world and has been given various folk names: in Burma (where it is called yaun ), Indonesia, Thailand 
(bah-tsche ), the Philippines ( mali-mali ), indigenous tribes in 
Siberia, Russia ( myriachit ), and among the Ainu in Japan (who call 
itimu).The latah  reaction is found predominantly among women,

itimu).The latah  reaction is found predominantly among women, 
although men may occasionally be involved. It was found that latah
tends to run in families. In the past, it was primarily young women who were involved in latah . Most of the subjects found now are 
beyond middle age. Most cases are found in rural areas. Some develop latah  reactions insidiously, without any precipitating 
events, whereas others symptoms occur after they endure psycho-logically stressful events. The loss of a signiﬁ  cant person usually 
occurs shortly before the ﬁ  rst experience of latah  reaction. Once 
the reaction is experienced, it becomes habitual, and, thereafter, any sudden stimulation may provoke it. Hearing a sudden noise or being suddenly touched or poked by others may cause latah .
Throwing a rope or other snake-like object in front of the person or simply shouting snake! will sufﬁ  ciently startle the person to start

Throwing a rope or other snake-like object in front of the person or simply shouting snake! will sufﬁ  ciently startle the person to start 
alatah  reaction.
The condition may last for several minutes or several hours if the 
person is continuously provoked. After the dissociative reaction is over, the subject usually claims amnesia and is puzzled about what had happened. Often, the subject is very apologetic and embar-rassed for the (socially) inappropriate things he or she may have said (sexually coloured, dirty words) or done (such as touching men) during the attack.
(ii) Aetiological speculations
Anthropologists have tried to understand the latah  condition from 
a cultural point of view. It has been pointed out that the latah
reaction is remarkably congruent with the cultural themes empha-sized, but in a paradoxical way. It is a peculiarly appropriate means of communicating marginality to others. The latah  subjects are

reaction is remarkably congruent with the cultural themes empha-sized, but in a paradoxical way. It is a peculiarly appropriate means of communicating marginality to others. The latah  subjects are 
engaging in a performance, a role, and theatre, a culture-speciﬁ  c 
idiom expressing marginality while simultaneously reafﬁ  rming 
normative boundaries. The traditional polygamous Malay extended family structure is male dominated. Within this cultural system, latah  is socially accepted as a female attention-seeking response, 
one of the few permissible overt, excitable, aggressive, and/or sexual demonstrations. In other words, latah  is a culturally sanc-
tioned emotional outlet for females. It is also a culturally elaborated unique behaviour.
(21)
Cultural inﬂ  uence of prevalent occurrence of disorders 
(pathofacilitating effects)
This category includes several conditions that are commonly

(21)
This category includes several conditions that are commonly 
known as psychiatric disorders. There is nothing particular about them in terms of clinical manifestation (thus, they are not speciﬁ  c
orunique  disorders). However, their prevalence is influenced 
strongly enough by cultural factors that they may be viewed as heavily culture-related syndromes, rather than merely ordinary
psychiatric disorders. Among this group of disorders, massive hysteria, group suicide, alcohol-related problems, or substance abuse are some of the examples.
Cultural interpretation of certain mental conditions 
(pathoreactive effect)
(a) Ataques de nervios (attack of nerves)
The folk name, ataques de nervios , literally meaning attack of 
nerves, refers to a stress-induced, culturally shaped unique emotional reaction with mixed anxiety-hysterical features.
(22)

(22)
This is an illness category used frequently by Hispanic people. 4.16 culture-related specific psychiatric syndromes

SECTION 4  clinical syndromes of adult psychiatry 984
Initially observed among Puerto Rican army recruits, it was also 
labelled Puerto Rican syndrome. This condition typically occurs at funerals, in accidents, or in family conﬂ  icts, and calls forth family 
or other social supports. Commonly experienced symptoms include shaking, palpitations, a sense of heat rising to the head, and numbness, symptoms resembling a panic attack. The individual may shout, swear, and strike out at others, and ﬁ  nally fall to the 
ground, manifesting convulsion-like movements.
Based on clinical study, it has been reported that most of the 
patients (about 80 per cent) were female. From a clinical, diagnostic point of view, according to DSM-III-R criteria, the condition belongs to many subtypes of disorders, including panic disorder, recurrent major depression, generalized anxiety disorder, non-speciﬁ  c anxiety disorder, and others. Because the clinical picture

is of a mixed, rather than a speciﬁ  c, nature, it may be interpreted 
simply as a folk label for an emotional reaction based on psychore-active effect. It may be understood as an acute episode of social and psychological distress related to upsetting or frightening events in the family sphere. Focusing on symptoms alone misses what is most salient and meaningful about illness categories.
(b) Hwabyung (ﬁ  re sickness)
Hwa-byung  in the Korean language literally means ﬁ  re (hwa) sick-
ness ( byung ). Based on a traditional Chinese medical concept that 
is still prevalent in Korea, that an imbalance among the five elements within the body (metal, wood, water, ﬁ  re, and earth) may 
cause physical disorders, laypeople in Korea use the folk term ﬁ  re 
sickness to describe ill conditions. This is a folk idiom of distress characterized by a wide range of somatic and emotional symptoms. About three-fourths of the patients that complained of hwabyung

were women, who linked their conditions to anger provoked by domestic problems, such as their husbands’ extramarital affairs and strained in-law relationships. Culturally, it has been explained that male chauvinism has always been dominant in Korean society, and women tend to suffer from their vulnerable status. When a housewife is mistreated by her husband or is having troubles with 
her in-laws, she has to suppress her emotional reactions so that 
there will be no disturbance in the stability of the family. As a woman, she is taught to accept defeat, bear frustration, and sup-press her hatred. As a result, accumulated resentment ( hahn  in 
Korean) becomes a major issue for some women. This is the core dynamic for understanding hwabyung .
(23)

(23)
Cultural factors may indirectly contribute to the occurrence of 
particular psychological problems that are encountered by Korean women, but through pathoreactive effect, emotional reaction was labelled by laymen as an indication of ﬁ  re sickness ( hwabyung ).
(c) Susto (soul loss)
Susto  is a Spanish word that literally means fright. The term is 
widely used by people in Latin America to refer to the condition of loss of soul.
(24) It is based on the folk belief that every individual

(24) It is based on the folk belief that every individual 
possesses a soul, but, through certain experiences, such as being frightened or startled, a person’s soul may depart from the body. As a result, the soul-lost person will manifest certain morbid mental conditions and illness behaviour. The remedy for such a condition is to recapture the soul through certain rituals. The concept of loss of soul as a cause for sickness is prevalent around the world, and that terms similar, or equivalent, to susto  are found 
widely distributed across many different cultural groups, such as el miedo  (fright) in Bolivia, lanti  in the Philippines, or mogo laya  in 
Papua New Guinea.
It should be pointed out that, although the cause is attributed to

It should be pointed out that, although the cause is attributed to 
spiritual-psychological reasons relating mostly to a frightening experience or misfortune, from a clinical point of view, the mani-fested syndrome is quite heterogeneous, without a commonly shared syndrome. The victim may manifest loss of appetite, sleep disturbance, reduced strength, absentmindedness, headache, dizzi-ness, or other somatic symptoms, as well as emotional symptoms of depression, anxiety, or irritability. Therefore, strictly speaking, it is not a culture-related speciﬁ  c syndrome derived from psychogenic 
or psychoplastic effects. It is culture-related only in the sense that 
the morbid condition is interpreted after the fact according to folk concepts of aetiology and certain ways of regaining the lost soul, such as rituals, are offered. Therefore, the role of culture is interpretation of and reaction to the illness.
Diagnosis and classiﬁ  cation issues

Associated with the increased awareness of the impact of culture 
on psychiatric classiﬁ  cations, there is controversy regarding how 
to deal with culture-related speciﬁ  c syndromes from a diagnostic 
point of view.(12) Some clinicians feel strongly that various known 
culture-bound syndromes (such as koro or hwabyung ) should be 
ofﬁ cially recognized and included in the present classiﬁ  cation 
system.
However, it needs to be pointed out that the present DSM classi-
ﬁ cation system is based on the descriptive approach, categorizing 
psychiatric disorders by certain sets of manifested symptomatology. If we try to ﬁ  t culture-related speciﬁ  c syndromes into the catego-
ries of the existing classiﬁ  cation system or try to create new catego-
ries of disorders, they will be classiﬁ  ed as NOS (not otherwise 
speciﬁ  ed) or, at best, as variations of presently recognized disor-

ders. Most importantly, by squeezing the culture-related speciﬁ  c 
syndromes into the descriptive-oriented classiﬁ  cation system, we 
will lose the unique meaning of the syndromes from a cultural 
perspective.
(25)
Culture-related speciﬁ  c syndromes in western societies
Another point that must be made is that, by deﬁ  nition, culture-
related speciﬁ  c syndromes should be able to be discovered every-
where, as every society, no matter East or West, has its own culture. However, the trend has been to consider that most culture-related speciﬁ  c syndromes (such as koro,amok , or dhat  syndromes) occur 
in non-western societies. This is because they were considered peculiar phenomena observed in areas previously colonized by western people and they simply did not ﬁ  t the classiﬁ  cation system

in non-western societies. This is because they were considered peculiar phenomena observed in areas previously colonized by western people and they simply did not ﬁ  t the classiﬁ  cation system 
developed for Euro-American populations. This trend is now changing. There is an increased interest in recognizing syndromes in our own western cultures that are heavily culture-related.
(26)
Several psychiatric disorders have been suggested by various schol-ars for consideration as western culture-related syndromes. These include: anorexia nervosa, obesity, drug-induced dissociated states, and multiple personality, disorders that are seldom observed or concerned in non-western societies. Because these conditions are already recognized in the existing western nosological system, they are, in a sense, not viewed as speciﬁ  c syndromes. However,

985
they can be viewed as culture-related psychiatric conditions 
that are inﬂ  uenced by the pathoelaborative, pathofacilitative, or 
pathoplastic effects of western culture.
Clinical implications for general psychiatry
Even though the encounter of culture-related speciﬁ  c psychiatric dis-
order in our daily psychiatric practice is relatively rare, the purpose of examining such speciﬁ  c syndromes has its signiﬁ  cant purpose and 
implications. Through such unique examples, it helps us to appreciate the cultural attribution to the stress formation, reaction pattern, symptom manifestation, occurrence of frequency of disorders, and reaction to the disorders. It also concerns how to work on therapy for the disorder by complying patient’s cultural background.
Tseng, W.S. (2001). D: 13. Culture-related speciﬁ  c syndromes. In Handbook 
of cultural psychiatry  (ed. W.S. Tseng), pp. 211–63. Academic Press, 
San Diego.

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London.4.16 culture-related specific psychiatric syndromes

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and
1VOLUME 2

Reproduction and Department of Psychiatry, University of Oxford 
London, UK 

xxiii
Henry O’Connell Consultant Psychiatrist, Co. Tipperary, Ireland 

5.1 Mind–body dualism, psychiatry, 
992
995
Per Fink
Christopher Bass and David Gill
 5.2.10 Neurasthenia  1059
 5.3 Medical and surgical conditions and treatments 
associated with psychiatric disorders  1065

Allan House 5.3.2 Psychiatric aspects of neurological disease  1071
 5.3.4 Medical conditions associated with 
psychiatric disorder   1081
1096
1105
1128

1128
Pier Maria Furlan and Luca Ostacoli
 5.7 The organization of psychiatric services for general hospital departments  
1144
Frits J. Huyse, Roger Kathol, 
Wolfgang Söllner, and Lawson WulsinSECTION 5
Psychiatry and 
Medicine

5.1
Patients usually attend doctors because they are concerned about 
symptoms. When these symptoms are associated with persistent distress or disability we refer to the patient as having an illness. When assessing the patient’s illness the doctor aims to make a diagnosis, on the basis of which management can be planned and prognosis made. The diagnoses available to doctors are conven-tionally deﬁ  ned as either ‘medical’ or ‘psychiatric’ . This division 
of illness into two types is such an accepted feature of current medical practice that we tend to take it for granted. But is it really the best way to think about patients’ illnesses and to plan their care?
In order to answer this question we will examine what is meant 
by ‘medical’ and ‘psychiatric’ diagnoses and the assumptions under-pinning this division. The disadvantages of this dualistic approach 
will be considered and solutions proposed.
Diagnosis
Medical diagnosis

Diagnosis
A medical diagnosis is a label for a condition that is: (a) conven-
tionally treated by medical doctors and (b) listed in the classiﬁ  cations 
of medical conditions such as ICD-10. Most medical diagnoses are based on identiﬁ  able bodily pathology (abnormal structure 
and/or function). Therefore, to make a medical diagnosis (such as cancer) doctors will seek speciﬁ  c bodily symptoms before con-
ﬁ rming the presence of bodily pathology with physical signs and 
biological investigations (such as X-rays).
Psychiatric diagnosis
Similarly a psychiatric diagnosis is a label for a condition that is: (a) conventionally treated by psychiatrists and (b) deﬁ  ned in the 
psychiatric diagnostic classiﬁ  cations of ICD and DSM. Psychiatric

psychiatric diagnostic classiﬁ  cations of ICD and DSM. Psychiatric 
diagnoses are not based not on bodily pathology. They are however associated with the idea of ‘psychopathology’ , that is proposed abnormalities of the mind. Unlike bodily pathology these abnor-malities of the mind cannot be objectively identiﬁ  ed and have to be 
inferred from the patient’s mental symptoms and their behaviour. Investigations play little or no role in diagnosis. Psychiatric diagnoses are therefore deﬁ  ned on the basis of symptoms and 
syndromes.When is an illness psychiatric?
Why are some illnesses regarded as ‘mental’ or ‘psychiatric’ as opposed to ‘medical’? Examination of the criteria for diagnoses listed as psychiatric reveals that readily observable factors common to most ‘psychiatric’ illnesses are:
◆ an absence of known bodily pathology
◆ an abnormal mental state as inferred by the patient’s report
◆ a presentation with disturbed behaviour
Mind–body dualism

The underlying assumption of this dichotomous view is that it is both valid and useful to divide human illnesses into those of the body and those of the mind.
(1) This idea of mind–body dualism is 
commonly attributed to the writings of the philosopher Descartes. So-called Cartesian dualism has exerted a profound inﬂ  uence on 
Western medical thinking and still shapes our thinking, training, and service provision.
However, dualism is at best an oversimpliﬁ  cation and at worst 
a source of serious theoretical and practical problems. It may be argued that there is no such thing as a purely ‘bodily’ or purely ‘mental’ illness and that all illnesses have mental and bodily aspects.
(2) Furthermore, the assumption that bodily symptoms

(2) Furthermore, the assumption that bodily symptoms 
indicate bodily pathology and that mental symptoms indicate psychopathology gives rise to speciﬁ  c problems: (a) when bodily 
symptoms occur without bodily pathology and (b) when mental 
symptoms occur together with bodily pathology (see Table 5.1.1).
Bodily symptoms with no bodily pathology: 
somatization
When patients present with bodily symptoms and bodily pathology 
is conﬁ  rmed they are given a medical diagnosis. When patients 
have bodily symptoms but there is no evidence of bodily pathology the terms ‘somatization ’ or ‘somatoform disorder’ are used to 
describe their illness. It is unclear, however, whether these illnesses are properly regarded as ‘psychiatric’ or as ‘medical’ as they do not clearly fulﬁ  l criteria for either. One solution to this dilemma is to

allocate these illnesses to psychiatry. The assumption is made that their somatic symptoms are really explained by psychopathology. The absence of mental symptoms, from which psychopathology Mind–body dualism, 
psychiatry, and medicine

990
can be inferred, is explained by the idea that the psychopathology is 
hidden and ‘converted’ into bodily symptoms by a process called ‘somatization’ (literally making the mental somatic). Clearly these are questionable assumptions.
(3)
A second solution is to assume that the patients really do have 
bodily pathology in some form (even though is it unknown) and to give them a medical diagnosis of a so-called ‘functional disorder’ such as ﬁ  bromyalgia.
(4) As with somatization this approach is based 
on questionable assumptions.
A third, and all too common solution, is for the patient to be 
rejected as ‘not really ill’ by both psychiatry and medicine. They then end up in a no-man’s land between specialities. The inadequacy of all three solutions has been particularly well illustrated by the controversy and conﬂ  ict surrounding the condition called Chronic 
Fatigue Syndrome (CFS) or Myalgic Encephalomyelitis (ME).
(5)
Mental symptoms and bodily pathology: comorbidity

(5)
When a patient has both bodily pathology and mental symptoms they are given both a medical diagnosis (based on the bodily pathology) and a psychiatric diagnosis (based on presumed psy-chopathology). This idea of ‘comorbidity’ gives rise to both theo-retical and practical problems, however.
The theoretical problem concerns the psychiatric diagnosis. T o 
make this diagnosis the doctor must identify symptoms, which are considered to be evidence of psychopathology. However, some symptoms may be considered as evidence of both psychopathology and bodily pathology. For example, a patient has mental symptoms of low mood and worthlessness, and a medical diagnosis of cancer, based on bodily pathology. Should the patient’s weight loss be counted toward a psychiatric diagnosis of depression or regarded as a symptom of his cancer? There is no generally agreed answer to

this conundrum (although a variety of ways of addressing it have been proposed
(6)), probably because it is a manifestation of the 
fundamentally ﬂ  awed dualistic assumption.
The main practical problem that results from making two diag-
noses is a failure to adequately treat the patient. Depressive disor-der comorbid with a chronic medical condition is a major cause of morbidity. However, the patient’s need for psychiatric treatment often goes unmet
(7) because the patient is considered to have 
two illnesses, each requiring diagnosis and treatment by a different speciality and the treatment of the medical condition takes precedence.
Solutions to dualism
Theoretical solutions
New scientiﬁ  c knowledge, such as the demonstration of a bodily 
(neural) basis to many ‘mental’ symptoms is increasingly rendering crude dualistic thinking theoretically untenable.(8) Mind and brain

(neural) basis to many ‘mental’ symptoms is increasingly rendering crude dualistic thinking theoretically untenable.(8) Mind and brain 
are coming to be regarded as two sides of the same coin—the mind/brain. This paradigm shift implies that ‘psychiatric’ illnesses are no 
more distinct from ‘medical conditions’ than the nervous system is separate from the rest of the body. Hence, there is a need for psy-chiatry to become less ‘brain-less’ and for medicine to become less 
‘mind- less’ .
(9) According to this new way of thinking, all symptoms, 
whether previously regarded as ‘bodily’ or ‘mental’ are in fact prod-ucts of the mind/brain’s integration of bodily, psychological, and social information. Therefore to speak of ‘medical’ and ‘psychiatric’ symptoms makes no sense. Symptoms are just symptoms.
If this paradigm shift is to be fully translated into clinical practice 
a new uniﬁ  ed classiﬁ  cation system is needed that would be used by

a new uniﬁ  ed classiﬁ  cation system is needed that would be used by 
both medicine and psychiatry. One way of achieving this might be to create a multi-axial system as is currently used by DSM-IV . However, rather than using separate axes for psychiatric and medi-cal diagnoses, separate axes would be used for symptoms (not distin-guishing between medical and psychiatric) and bodily pathology.
(10)
Other axes could be added to ensure that other important informa-tion is included. An example is shown in Table 5.1.2.
Practical solutions

(10)
For the present we must accept that dualism continues to shape our every day thinking, practice, and service organization. It is impor-tant therefore, that the psychiatrist is aware of the practical prob-lems that result and is equipped with ways of addressing them. In this regard the psychiatrist is especially well placed to make a major contribution to the care of all patients by ensuring that biological, psychological, and social aspects of illness are considered in every case. This so-called ‘biopsychosocial’ formulation was ﬁ  rst pro-
posed by Engel.
(11) A further enhancement of this formulation is to

(11) A further enhancement of this formulation is to 
divide the aetiological factors into those that predisposed the patient to the illness, those that precipitated or triggered it, and those that are perpetuating it. The last group of causes is a target for treatment and the ﬁ  rst two for prevention. A useful diagram 
that lists factors to consider in a biopsychosocial formulation is shown in Table 5.1.3.
Service solutions
Finally, the consequence of the professional and organizational separation of medicine and psychiatry has been a major obstacle to the integrated care of patients, especially those with comorbidity and somatoform disorders. One service solution has been the establishment of so-called liaison (linking) psychiatry services to general hospital inpatient units. Another is the increasing integra-tion of psychological management into chronic illness manage-ment programmes.
(12) However truly integrated care remains the

(12) However truly integrated care remains the 
exception rather than the rule.SECTION 5  psychiatry and medicine
Table 5.1.1  Diagnoses symptoms and bodily pathology
Symptoms Bodily pathology Diagnosis
Bodily symptoms Present
AbsentMedical diagnosis
Somatization
Mental symptoms Present
AbsentComorbidity
Table 5.1 .2 A proposed multi-axial diagnostic system for use by 
both psychiatry and medicine
Axis 1 Symptoms or syndrome, e.g. chronic fatigue or depression
Axis 2 Bodily pathology, e.g. cancerAxis 3 Biological factors, e.g. autonomic arousalAxis 4 Psychological factors, e.g. beliefsAxis 5 Social and situational factors, e.g. bereavement

991
It has been taken for granted that it is appropriate and desirable to 
separate patients’ illnesses into medical and psychiatric types. Such an approach has had advantages in allowing specialization of train-ing and service planning but has also created obstacles to effective patient care. It is important that practising psychiatrists are aware of these obstacles and ways of overcoming them. It also seems increasingly likely that in time better understanding of neuro-science will make dualism increasingly theoretically untenable and that a better understanding of chronic illness management will make it practically redundant. Only then will psychiatry become fully reintegrated with the rest of medicine.
White, P .D. (2005). Biopsychosocial medicine . Oxford University Press, 
Oxford.
Damasio, A.R. (1994) Descartes’ error . GP Putnam’s Sons, New Y ork.References
 1. Miresco, M.J. and Kirmayer, L.J. (2006). The persistence of mind-brain

Oxford.
 1. Miresco, M.J. and Kirmayer, L.J. (2006). The persistence of mind-brain 
dualism in psychiatric reasoning about clinical scenarios. The American 
Journal of Psychiatry ,163, 913–8.
 2. Wade, D.T. and Halligan, P .W. (2004). Do biomedical models of illness 
make for good healthcare systems? British Medical Journal ,329, 1398–
401.
 3. DeGucht, V . and Fischler, B. (2002). Somatization: a critical review of 
conceptual and methodological issues. Psychosomatics ,43, 1–9.
 4. Wessely, S., Nimnuan, C., and Sharpe M. (1999). Functional somatic 
syndromes: one or many? Lancet ,354, 936–9.
 5. Sharpe, M. (2002). The English Chief Medical Ofﬁ  cer’s Working 
Parties’ report on the management of CFS/ME: signiﬁ  cant 
breakthrough or unsatisfactory compromise? Journal of Psychosomatic 
Research ,52, 437–8.
 6. Cohen-Cole, S.A., Brown, F.W., and McDaniel, J.S. (1993). Diagnostic

 6. Cohen-Cole, S.A., Brown, F.W., and McDaniel, J.S. (1993). Diagnostic 
assessment of depression in the medically ill. In Psychiatric care of the 
medical patient  (eds. A. Stoudemire and B. Fogel), pp. 53–70. Oxford 
 7. Moussavi, S., Chatterji, S., Verdes, E., et al. (2007). Depression, chronic 
diseases, and decrements in health: results from the World Health 
Surveys. Lancet ,370, 851–8.
 8. Kendler, K.S. (2001). A psychiatric dialogue on the mind-body 
problem. The American Journal of Psychiatry ,158, 989–1000.
 9. Eisenberg, L. (1986). Mindless and brainless in psychiatry. British 
Journal of Psychiatry ,148, 497–508.
10. Sharpe, M., Mayou, R., and Walker, J. (2006). Bodily symptoms: new 
approaches to classiﬁ  cation. Journal of Psychosomatic Research ,60,
353–6.
11. Engel, G.L. (1977). The need for a new medical model: a challenge for

353–6.
11. Engel, G.L. (1977). The need for a new medical model: a challenge for 
biomedicine. Science ,196, 129–96.
12. Von Korff, M., Glasgow, R.E., and Sharpe, M. (2002). Organising care 
for chronic illness. British Medical Journal ,325, 92–4.5.1 mind–body dualism, psychiatry, and medicine
Table 5.1.3  A biopsychosocial formulation
Main factors Subfactors Predisposing Precipitating Perpetuating
Biological Disease
physiology
Psychological Cognition
moodbehaviour
Social Interpersonal
social and 
occupational
health care 
system

Contents
 5.2.1 Somatoform disorders and functional symptoms
 5.2.2 Epidemiology of somatoform disorders and 
other causes of unexplained medical symptoms
 5.2.3 Somatization disorder and related disorders
Per Fink
 5.2.4 Conversion and dissociation disorders
 5.2.5 Hypochondriasis (health anxiety)
 5.2.6 Pain disorder
 5.2.7 Chronic fatigue syndrome
 5.2.8 Body dysmorphic disorder
Katharine A. Phillips, M. D.
 5.2.9 Factitious disorder and malingering
 5.2.10 Neurasthenia
5.2.1  Somatoform disorders 
and functional symptoms
Non-speciﬁ  c symptoms that are not explained by organic pathology 
are extremely frequent in the general population(1) and in all

are extremely frequent in the general population(1) and in all 
medical settings. Most are transient, but a substantial minority is persistent, disabling, and often associated with frequent consultation. They are likely, especially when there are multiple unexplained sym-
ptoms, to be associated with psychiatr ic disorder (see Chapter 5.2.3). 
They are widely regarded as difﬁ  cult to treat but only a very small 
proportion is seen by psychiatrists and psychologists.
This chapter covers general issues relating to functional symp-
toms and syndromes and their psychiatric associations. The following chapters provide more detail about the more speciﬁ  c 
forms of somatoform disorder and about functional syndromes (pain, chronic fatigue).
Terminology of functional symptoms
The terminology is unsatisfactory.(2) These symptoms are often

The terminology is unsatisfactory.(2) These symptoms are often 
referred to as ‘medically unexplained symptoms’ . This usage has the advantage of describing the clinical problem without assumptions of aetiology, but it is unsatisfactory in that it wrongly implies that there is no medical explanation. Other generally used terms include somatization, somatoform symptoms, and functional overlay. It is perhaps most satisfactory to refer to functional symptoms and functional syndromes.
This chapter is concerned with functional symptoms whether or 
not they are associated with psychiatric disorder.
Aetiology
A traditional Western dualist view of aetiology as being either physical or psychological, continues to inﬂ  uence clinical practice 
and current psychiatric classiﬁ  cations (see Chapter 5.1). In western

and current psychiatric classiﬁ  cations (see Chapter 5.1). In western 
countries, this view has resulted in great problems in psychiatric and lay understanding, in taxonomy, and in the treatment of ‘unex-plained’ symptoms. It has also caused bewilderment in cultures that do not share this dualist approach.
An increasingly widely held alternative view, for which there 
is compelling evidence, is that functional symptoms result from the interaction of physiological, pathological, and psychosocial variables.
(2) A primary bodily sensation or concern (Table 5.2.1.1) 
is then attributed or interpreted as being of sinister signiﬁ  cance

is then attributed or interpreted as being of sinister signiﬁ  cance 
with resulting subjective symptoms, disability, and behavioural and emotional consequences. For example, awareness of normal heart rate increase due to excitement or anxiety can result in, on the one hand, panic and, on the other, worry about heart disease, restric-tion of daily activities, and repeated consultation to seek investigation Somatoform disorders and 
other causes of medically unexplained symptoms5.2

993
and reassurance. The role of these factors may vary over time dur-
ing the course of any individual clinical problem.
There is considerable evidence on the ways in which psychological
processes affect the interpretation of physical symptoms, whatever the underlying (major or minor) pathology or physiological processes. Cognitive-behavioural formulations emphasize the cen-tral signiﬁ  cance of health anxiety and suggest that feedback of the 
physiological, cognitive, affective, and behavioural consequences of this anxiety can reinforce the physical symptoms as well as their effects on everyday life.
The process of interpretation of a bodily sensation or fear is 
affected by several sets of factors:
◆ the individual’s medical experience and beliefs
◆ social circumstances (Table 5.2.1.2)
◆ personality and mental state
Once symptoms have developed they may be maintained by

Once symptoms have developed they may be maintained by 
behavioural and psychological factors and also by the reactions of others. As with other forms of anxiety, neurobiological mecha-nisms may perpetuate and complicate the initial presentation.
Simple reassurance is often ineffective especially in those who, by 
reason of personality, are inclined to worry about their health. Misconceptions are frequently reinforced and maintained by the lack of any medical explanation for worrying symptoms or by ambiguous or contradictory advice.
The association with psychiatric disorder

The majority of functional symptoms in general populations are short lived and not associated with psychiatric disorder. There is now considerable evidence both from smaller local studies and international collaborative research that the more severe and  disabling functional symptoms are associated with anxiety and 
depressive disorder, and that this relationship is strongest for those who have the greatest number of ‘unexplained’ symptoms. This is so for all ethnic groups and cultures studied.
(1) There are also asso-
ciations with the somatoform disorders as described below.
Classiﬁ  cation of unexplained symptoms
The classiﬁ  cation of persistent and disabling functional symptoms 
has taken two parallel approaches.
(a) Medical descriptive syndromes

These are very numerous, clinical patterns and terms overlap and some include assumptions about aetiology. There are cultural dif-ferences in the deﬁ  nition and naming. There is little evidence for 
the validity of separate syndromes. Lay pressure groups have increasingly claimed speciﬁ  c syndromes, such as alleged sensitivity 
to dental amalgam and many ‘food allergies’ , which are more likely to be due to their own predicaments and the apparent lack of suc-cess of conventional medicine.
(3) A small number of syndromes 
have now received operational diagnostic criteria which have proved valuable in clinical understanding and in planning treat-ment, for example the criteria for chronic fatigue (Chapter 5.2.7).
(b) Psychiatric classiﬁ  cation
This covers both well established categories, such as anxiety and

This covers both well established categories, such as anxiety and 
depressive disorders, and the new concept, ﬁ  rst introduced in 
DSM-III, of somatoform disorder.
(i) Somatoform disorder
Somatoform disorders (Table 5.2.1.3) were seen as speculative and provisional in DSM-III. The deﬁ  ning feature was ‘physical 
symptoms suggesting a physical disorder for which there are no demonstrable organic ﬁ  ndings on known physiological mechanisms, and for which there is strong evidence, or a strong presumption, that the symptoms are linked to psychological factors or conﬂ  icts’ .
The original DSM-III classiﬁ  cation was relatively narrow but 
subsequent revisions of DSM and ICD-10 have incorporated non-speciﬁ  c categories which have turned out to be much more 
prevalent in all settings.Table 5.2.1.1  Causes of bodily sensations
Major pathology
Minor pathology
Physiological processes, for example:

 Sinus tachycardia and benign minor arrhythmias Effects of fatigue
 Hangover
 Effects of overeating
 Effects of prolonged inactivity
 Autonomic effects of anxiety
 Lack of sleep
Table 5.2.1.2  Illness experience, which may affect the interpretation 
of bodily sensations and concern
Childhood illness
Family illness and consultation in childhood
Childhood consultation and school absence
Physical illness in adult lifeExperience and satisfaction with medical consultation
Illness in family and friends
Publicity in television, newspapers, etc.
Knowledge of illness and its treatmentTable 5.2.1.3  Categories of somatoform disorders in ICD-10 and 
DSM-IV
Somatization disorder Somatization disorder
Undifferentiated somatoform 
 disorderUndifferentiated somatoform disorder
Hypochondriacal disorder Hypochondriasis
Somatoform autonomic

Somatoform autonomic 
 dysfunction—
Persistent pain disorder Pain disorder associated with psychological 
 factors (and a general medical condition)
Other somatoform disorders Somatoform disorders not otherwise 
 speciﬁ  ed
— Body dysmorphic disorder— Conversion disorders
Neurasthenia —5.2.1 somatoform disorders and functional symptoms

SECTION 5  psychiatry and medicine 994
It is important to recall that somatoform disorder remains a pro-
visional grouping for statistical purposes rather than a grouping of categories that satisfy the normal requirements of disease entities. It nevertheless indicates a substantial clinical problem associated with considerable use of health care provisions.
(3)
(ii) Factitious disorder
DSM-III also introduced another new category of ‘factitious disor-der’ for self-inﬂ  icted physical problems. These are described in 
Chapter 5.2.9 and should be distinguished from deliberate falsiﬁ  ca-
tion for external gain— malingering . It must be remembered that 
patients with factitious disorder may also suffer from unexplained symptoms attributable to somatoform or other psychiatric disor-ders and, indeed, not uncommonly also report symptoms of undoubted physical illness.
Somatoform disorders in DSM and ICD
There are substantial differences between the use of subcategories in DSM and ICD.

(4) Neurasthenia is included in ICD-10 but is 
not used in any section of DSM-IV; conversion disorder is a somatoform disorder in DSM-IV but not in ICD. Both classiﬁ  ca-
tions include both relatively speciﬁ  c categories (e.g. somatization 
disorder  and hypochondriasis ) and also several very vaguely deﬁ  ned 
non-specific categories. These latter include Undifferentiated 
Somatoform Disorder ,Somatoform Autonomic Dysfunction  (ICD-10 
only), and Other Somatoform Disorders . Although these latter have

only), and Other Somatoform Disorders . Although these latter have 
attracted less clinical and research attention, they are by far the most common forms of somatoform disorder in all epidemiological studies. So broad are the criteria that it is possible to use these categories for almost all persistent unexplained physical symptoms. Epidemiological comparisons of ICD and DSM show that the use of their rather different criteria results in substantially different prevalences of somatoform disorder in community and primary 
care populations.
Problems in the deﬁ  nition of 
somatoform disorder
It is widely recognized that there are serious problems(2) in the 
overall concept of somatoform disorders and in the deﬁ  nition of 
subcategories:
◆ There is no unifying theoretical basis for the whole category; it is

◆ There is no unifying theoretical basis for the whole category; it is 
a disparate group of problems that are not easily ﬁ  tted into other 
parts of the classifcations.
◆ Comorbidity is very common, especially with anxiety disorder, 
depressive disorder, and personality disorder.
◆ Some types of somatoform disorder could be more satisfactorily 
reassigned to other parts of the classification (for example hypochondriasis might be renamed health anxiety and moved to anxiety disorder).
◆ The deﬁ  nitions of the less speciﬁ  c categories (pain disorder,

◆ The deﬁ  nitions of the less speciﬁ  c categories (pain disorder, 
Undifferentiated Somatoform Disorder) do not include any psychological criteria. Instead they rely on the description and the number of physical symptoms, the same symptoms that are used to make accompanying Axis III diagnoses. Somatization disorder has attracted disproportionate attention, but appears to be no more than an uncommon, arbitrary and unreliable extreme 
of the spectrum of multiple physical symptoms.
◆ Criteria have little meaning for cultures that do not share the 
western presumption of the separation of body and mind.
It has become apparent that the present classiﬁ  cations have no 
value in guiding treatment and that they are both confusing and unpopular with patients and with those who treat them.
DSM-V and ICD-11 can be expected to make large changes 
which will depend on the resolution of conceptual arguments and substantial further research. It is hoped that the new classiﬁ  cation

which will depend on the resolution of conceptual arguments and substantial further research. It is hoped that the new classiﬁ  cation 
and terminology will be more reliable and valid and also be much more meaningful and acceptable.
(2)
It is likely that the more speciﬁ  c subcategories (hypochondriasis, 
body dysmorphic disorder) will be reassigned to other parts of the classiﬁ  cation and that there will be modiﬁ  cations in their criteria. 
The greatest problems relate to the much more prevalent non-speciﬁ  c 
categories. There is a consensus that a more rational operational approach is required to categorize multiple symptoms which should result in either a renamed grouping on Axis I or more logically a transfer to Axis III. It should be possible to give much greater prominence both in criteria and in accompanying text to underlying 
psychological and behavioural abnormalities.
Classiﬁ  cation in clinical practice

The following chapters in this section of the book describe syn-
dromes that have proved to have some administrative value despite the acknowledged lack of validity. Anxiety and depression are considered fully elsewhere. The recognition of anxiety and depres-sion is important because of the therapeutic implications.
In everyday clinical practice it is rarely necessary (or helpful) to 
attach a somatoform label. It is more useful to be able to provide brief descriptions of the clinical problem, since these can be used as a basis for formulating treatment:
◆ acute or chronic
◆ number of physical symptoms
◆ the nature and pattern of symptoms (i.e. clinical syndromes such 
as fatigue)
◆ association with anxiety disorder, depressive disorder, or other 
speciﬁ  c psychiatric disorder
◆ beliefs about cause
Assessment and treatment
The majority of those presenting unexplained symptoms in pri-

mary care require no more than medically appropriate assessment and reassurance (Table 5.2.1.4). The latter should convey to the patient that the symptoms are accepted as real and provide an explanation for their origin as well as answering the patient’s 
worries. It is also necessary to discuss the results of any negative 
investigations fully.
Symptoms that persist or recur despite reassurance are generally 
regarded as difﬁ  cult to treat. Continuing symptoms without any 
speciﬁ  c medical explanation are likely to conﬁ  rm and maintain 
worries about serious illness, which may be further exacerbated by secondary anxiety and behavioural consequences. Therefore

995
effective treatment depends upon sympathetic treatment that 
meets the needs of both the patient and the family. A multi-causal view of aetiology leads to conclusions about treatment and avoids psychiatric diagnoses that may be unacceptable to the patient. Much can be done by general practitioners or non-specialists.
The general principles of treatment (Table 5.2.1.5) are similar for 
all forms of unexplained symptoms, single or multiple, but indi-vidual treatment plans must take account of psychiatric diagnoses of anxiety or depression and the particular type of physical symptoms.
The treatments for particular forms of somatoform disorder are 
discussed in later chapters. It is important to be aware that the commonest type of somatoform disorder, Undifferentiated Somatoform Disorder is not discussed separately; treatment follows the general principles described in this and other chapters. 
The treatments of other functional syndromes such as irritable

The treatments of other functional syndromes such as irritable 
bowel syndrome, chronic fatigue, and atypical facial pain all depend on the therapist being familiar with these syndromes and being able to provide an appropriate combination of treatment methods. For example, the management of physical de-conditioning is central to the treatment of chronic fatigue, whereas antidepressant medi-cation has a major role in the treatment of atypical facial pain. The chapter on chronic fatigue (Chapter 5.2.7) is an example of a func-tional syndrome.
Much can be achieved by components of good non-specialist 
care, such as the following:
◆ discussion and explanation of the aetiology
◆ treatment of any minor underlying physical problem
◆ anxiety management (including tapes and handouts)
◆ advice on diary monitoring and graded return to full activities
◆ speciﬁ  c self-help programmes (e.g. chronic fatigue, irritable 
bowel syndrome)

◆ including relatives in the assessment, discussion of the nature of 
the problems, and explanations of the treatmentHowever, chronic and recurrent problems may need specialist 
treatment:
◆ psychotropic medication (antidepressants, anxiolytics)
◆ cognitive behavioural therapy
◆ interpretative psychotherapy (individual and group)
◆ speciﬁ  c psychiatric treatment for associated psychiatric and 
social problems
◆ programme to co-ordinate and control all medical care
There is a lot of evidence on the effectiveness of a range of treat-
ments in specialist care,(5,6) but there is much less evidence about

ments in specialist care,(5,6) but there is much less evidence about 
simple routine measures. The outlook for simpler syndromes of relatively recent onset is good, but the prognosis for very prolonged chronic, multiple, or recurrent syndromes (e.g. somatization disorder) is not as good. In these circumstances the control of medical care and the prevention of further iatrogenic disability may be more realistic than cure.
Mayou, R., Kirmayer, L.J., Simon, G., et al. (2005). Somatoform disorders: 
time for a new approach. American Journal of Psychiatry ,162, 847–55.
Maj, M., Akiskal, H.S., Mezzich, J., et al. (eds.) Somatoform disorders . Wiley, 
1. Üstün, T.B. and Sartorius, N. (1995). World health organization. Mental 
illness in general health care. An international study . Wiley, Chichester.

2. Mayou, R., Kirmayer, L.J., Simon, G., et al. (2005). Somatoform 
disorders: time for a new approach. American Journal of Psychiatry ,
162, 847–55.
3. Barsky, A.J., Orav, E.J., and Bates, D.W. (2005). Somatization increases 
medical utilization and costs independent of psychiatric and medical comorbidity Archives of General Psychiatry ,62, 903–10.
4. Fink, P ., Hansen, M.S., and Oxhoj, M.L. (2004). The prevalence of 
somatoform disorders among internal medicine patients. Journal of 
Psychosomatic Research ,56, 413–18.
5. Kroenke, K. and Swindle, R. (2000). Cognitive-behavioral therapy for 
somatization and symptom syndromes; a critical review of controlled clinical trials. Psychotherapy and Psychosomatics ,69, 205–15.
6. O’Malley, P .G., Jackson, J.L., Santoro, J., et al. (2005) Antidepressant

6. O’Malley, P .G., Jackson, J.L., Santoro, J., et al. (2005) Antidepressant 
therapy for unexplained symptoms and symptom syndromes. The
Journal of Family Practice ,48, 980–90.
5.2.2 Epidemiology of somatoform 
disorders and other causes of unexplained medical symptoms
While nearly every psychiatric syndrome may include some somatic 
signs or symptoms, a speciﬁ  c group of syndromes has been tradi-
tionally deﬁ  ned as somatoform. This group of disorders is distin-
guished by certain key features: prominent reporting of somatic Table 5.2.1.4  General principles of assessment
Consider psychological factors from the outset
Use appropriate physical investigation to exclude physical cause
Clarify psychological and physical complaints
Clarify previous personality and concerns about physical illness
Understand patient’s beliefs and expectationsIdentify depression or other psychiatric disorder
Identify psychosocial problems
Table 5.2.1.5  General principles of treatment

Emphasize that symptoms are real and familiar and that medical care is 
 appropriate
Minimize and control physical careOffer an explanation and discuss
Allow patients and families to ask questions
Discuss the role of psychological factors in all medical careTreat any primary psychiatric disorder
Agree a treatment plan5.2.2 epidemiology of somatoform disorders and other causes of unexplained medical symptoms

SECTION 5  psychiatry and medicine 996
symptoms, concern about medical illness, and frequent presenta-
tion to general medical providers. As in other categories of mental disorder, the boundaries between individual syndromes are more distinct in our systems of classiﬁ  cation than they are in nature. 
Understanding that various somatoform disorders often overlap, this review is organized according to the major categories of somatoform disorder described in the ICD and DSM classiﬁ  cation 
systems.
Somatization disorders
The term somatization has been used to refer to a variety of clinical phenomena. One traditional view defines somatization as an inability or unwillingness to express emotional distress,
(1) so that 
somatic symptoms are an alternative ‘idiom of distress’ . An alterna-tive view deﬁ  nes somatization as the presentation of somatic com-
plaints to medical providers in the presence of an occult anxiety or depressive disorder.

(2) A third view deﬁ  nes somatization as somatic 
symptoms, which have no clear medical explanation.(3) While these 
deﬁ nitions appear closely related, they identify somewhat different 
groups of patients. The third deﬁ  nition (presentation of unexplained 
somatic symptoms) is used by ofﬁ  cial systems of classiﬁ  cation and 
by most epidemiological studies, so this review will focus on that phenomenon.
Both the ICD and DSM classiﬁ  cation systems deﬁ  ne somatization 
disorder as a chronic condition characterized by the reporting of numerous unexplained somatic symptoms.
(4, 5) Recent versions 
of both classiﬁ  cation systems identify a core syndrome of somati-
zation (a persistent tendency to report multiple unexplained somatic symptoms) using a simpliﬁ  ed set of diagnostic criteria.
The reported prevalence of well-deﬁ  ned somatization disorder

The reported prevalence of well-deﬁ  ned somatization disorder 
appears to depend signiﬁ  cantly on the method used for assessment. 
Community and primary care surveys have typically relied on structured interviews to assess the lifetime prevalence of unexplained 
somatic symptoms. Community surveys in North America
(6)
and Western Europe(7, 8) have found prevalence rates of less than 
2 per cent with primary care surveys ﬁ  nding only slightly higher 
prevalence rates.(9) Data from the World Health Organization 
(WHO ) multicentre primary care survey indicate that recall during 
structured interviews may signiﬁ  cantly underestimate the lifetime 
prevalence of somatization symptoms.(10) More accurate recall 
of lifetime symptoms (by either repeated assessments or the use of medical records) might yield signiﬁ  cantly higher prevalence rates.
Correlates
The prevalence of somatization disorder and unexplained somatic

The prevalence of somatization disorder and unexplained somatic 
symptoms is typically twice as high in women as in men,(11, 12)  and 
this difference appears at time of menarche.(13) Community and 
primary care surveys demonstrate a substantial overlap between somatization disorder and anxiety and depressive disorders.
(7, 14, 15)
Anxiety and depressive disorders also predict the subsequent onset of somatization disorder.
(16)
Available data show a mixed picture regarding cross-national or 
cross-cultural differences in the prevalence of somatization. Studies of clinical samples ﬁ  nd that somatic symptoms are a common accompaniment of depressive and anxiety disorders worldwide.
(17–19)
The WHO primary care survey documented large differences in 
the prevalence of unexplained somatic symptoms with a markedly higher prevalence in South America than in Europe or the United States.
(9) That same study, however, found that the association

(9) That same study, however, found that the association 
between unexplained symptoms and symptoms of depression or anxiety was similar across a wide range of cultures and levels of economic development.
(14) One explanation for these apparently 
disparate ﬁ  ndings is that the prevalence of unexplained somatic 
symptoms (like the prevalence of anxiety or depressive disorder) varies widely across nations and cultures, but the association between somatic and psychological distress is universal. Countries or cultures with higher rates of anxiety or depressive disorders would be expected to have higher prevalence of somatization dis-order and other somatization syndromes. Given the consistent overlap between somatization disorders and other common mental disorders, some have questioned whether these conditions actually belong in a distinct category.

(20, 21)
Controversies and questions
Available data do not support a speciﬁ  c diagnostic threshold based 
on the number or distribution of unexplained somatic symptoms. An increasing number of somatic symptoms is consistently associated with increases in comorbid mood or anxiety disorder, functional impairment, and use of health services.
(14,15) Mindful of 
this continuum, both Escobar et al.(22) and Kroenke et al.(23) have 
described less restrictive somatization syndromes, which, despite their higher prevalence, are strongly associated with impairment and the use of health services. Both the ICD and DSM classiﬁ  cation 
systems describe subthreshold or less extreme forms of this condi-tion characterized by a smaller number of medically unexplained symptoms.
(5, 24)
Longitudinal data raise questions about the presumed stability

(5, 24)
Longitudinal data raise questions about the presumed stability 
or chronicity of somatization disorder or medically unexplained somatic symptoms. Traditional descriptions of somatization disorder emphasize its stability and chronicity. Data from the WHO primary care survey, however, suggest that individual somatization symptoms vary considerably over time.
(9) While the syndrome of 
somatization seemed somewhat more stable than anxiety and depressive disorders (typically regarded as episodic), only half of the primary care patients, satisfying Escobar’s criteria for somatiza-tion syndrome at the baseline assessment, continued to meet the criteria one year later.
Hypochondriacal disorders
Both the ICD and DSM classiﬁ  cation systems deﬁ  ne hypochon-
driasis by the triad of disease conviction, functional impairment, 
and refusal to accept appropriate reassurance.
Attempts to estimate the prevalence of hypochondriasis have been

Attempts to estimate the prevalence of hypochondriasis have been 
limited by the absence of proven standardized methods for stan-dardized assessment. Community surveys ﬁ  nd prevalence rates of 
1 per cent or less,
(25) while primary care surveys typically ﬁ  nd rates 
of approximately 5 per cent,(26, 27) while the WHO multicentre pri-
mary care survey(28) found an overall prevalence of only 0.8 per cent.

997
In reviewing data from the WHO survey, Gureje et al.(28) found that 
a less restrictive deﬁ  nition more than doubled the prevalence rate 
(to 2.2 per cent). Cases added by this relaxed deﬁ  nition did not dif-
fer signiﬁ  cantly from those satisfying CIDI/ICD criteria, suggesting 
that CIDI/ICD criteria may be somewhat too restrictive.
Despite the variation in prevalence, primary care surveys yield sim-ilar results regarding demographic correlates of hypochondriasis. 
The prevalence of hypochondriasis is 1.5 to 2 times as great in women as men but does not appear to vary signiﬁ  cantly with age.
(28)
While the ICD and DSM classification systems suggest that 
hypochondriasis is distinct from anxiety and depressive disorders, available data suggests considerable overlap. In every sample exam-ined, hypochondriasis is strongly associated with major depression, panic disorder, and generalized anxiety disorder.
(26,28–30)  Among

(26,28–30)  Among 
those with hypochondriasis, clinical features do not clearly distin-guish those with and without a comorbid psychiatric diagnosis.
(30)
In addition, changes over time in anxiety or depression are consis-tently associated with parallel changes in symptoms of hypochon-driasis.
(31) As with somatization disorders, some have recently 
argued that hypochondriasis be re-classiﬁ  ed as a form of anxiety 
disorder.(20,21)
Pain syndromes
While the ICD and DSM classiﬁ  cation systems both deﬁ  ne somato-
form pain disorders, the two systems differ in their descriptions of the clinical features. In the ICD diagnostic system, somatoform pain disorder is deﬁ  ned as persistent pain without clear medical 
explanation.
(5) The DSM system(4) speciﬁ  es that ‘psychological 
factors are judged to have an important role in the onset, severity, exacerbation, or maintenance of the pain’ . Both deﬁ  nitions are

factors are judged to have an important role in the onset, severity, exacerbation, or maintenance of the pain’ . Both deﬁ  nitions are 
somewhat problematic. Basic research on neural changes asso ciated with persistent pain raise doubts about the distinction between pain with and without a biomedical explanation.
(32) As discussed 
below, longitudinal research supports the view that persistent pain causes psychological disorder as much as it supports the DSM view that pain results from psychological distress. Recent epidemiologi-cal research has attempted to avoid questions of aetiology and has examined the prevalence and correlates of persistent pain.
Epidemiological studies consistently ﬁ  nd that pain syndromes are

Epidemiological studies consistently ﬁ  nd that pain syndromes are 
among the most common problems presented to general medical providers. Population surveys indicate that over 25 per cent of community residents suffer from recurrent or persistent pain symptoms and that 2 to 3 per cent experience disabling pain syndromes.
(33) The recent WHO primary care survey(34) found 
that approximately 20 per cent of primary care patients suffered from persistent pain (one or more pain symptoms present for most of the last 6 months). Pain syndromes are approximately twice as prevalent in women as in men.
(15)
The limited data available do not allow deﬁ  nite conclusions 
about cross-cultural or cross-national variability in pain  syndromes. Some studies have documented cross-national or cross-cultural 
differences based on small samples of patients treated for pain  syndromes—often in specialist pain clinics.
(35) The WHO primary

(35) The WHO primary 
care survey(34) included both the largest number of patients with 
pain syndromes as well as the broadest range of cultures and levels of economic development. In that study, both the prevalence and correlates of persistent pain varied widely across sites. No clear  pattern (e.g. a higher prevalence in developing or non-Western countries) was evident.
All available data indicate that pain symptoms are strongly associ-ated with anxiety and depressive disorders. This relationship has been consistently demonstrated in both community
(36) and pri-
mary care(34) studies across a broad range of cultural and socio-
economic divides. Psychological distress is most strongly associated with pain occurring at multiple sites and pain associated with func-tional impairment.
(37, 38)  While epidemiological studies strongly

(37, 38)  While epidemiological studies strongly 
support an association between pain complaints and psychological distress, this does not necessarily imply that pain is a consequence of psychological distress. Some studies ﬁ  nd that the presence of 
psychological distress predicts the onset of pain syndromes,
(39,40)
while others support the opposite relationship—that persistent pain predicts subsequent psychological disorder.
(41)
Other somatoform conditions
Speciﬁ  c somatoform syndromes
A number of speciﬁ  c somatic syndromes have been described 
over the last several decades. These speciﬁ  c syndromes are some-
times deﬁ  ned by the particular somatic symptoms experienced 
(e.g. ﬁ  bromyalgia, irritable bowel syndrome, chronic fatigue syn-

drome) and sometimes by particular beliefs about aetiology (e.g. multiple chemical sensitivity, systemic candidiasis, electrical allergy). In every case, controversy persists about whether the somatic symptoms should be considered ‘medically unexplained’ (that is to say a somatoform disorder). Community surveys sug-gest that non-speciﬁ  c symptoms (such as fatigue or diffuse mus-
culoskeletal pain) are common, but that the prevalence of strictly deﬁ ned syndromes (such as ﬁ  bromyalgia or chronic fatigue syn-
drome) varies considerably with the criteria applied.
(42, 43)  Most 
of these syndromes appear more often in women than in men.(44)
Both community(43, 44) and primary care surveys(45, 46) have found

Both community(43, 44) and primary care surveys(45, 46) have found 
several of these syndromes to be associated with anxiety and depressive symptoms. However, two studies of chronic fatigue
(47)
and irritable bowel(48) symptoms found that psychological dis-
tress was associated with seeking care for somatic symptoms rather than the presence or nature of the somatic symptoms themselves.
Body dysmorphic disorder or monosymptomatic 
hypochondriasis
Body dysmorphic disorder has recently been identiﬁ  ed as a distinct 
clinical entity. The limited epidemiological data available suggest signiﬁ  cant overlap with anxiety and depressive disorders.
(8, 50)
Prevalence estimates range from less than 1 per cent among unsel-
ected primary care patients,(8) to as high as 5 to 10 per cent among

(8, 50)
ected primary care patients,(8) to as high as 5 to 10 per cent among 
patients seeking cosmetic surgery(49) or outpatients with anxiety 5.2.2 epidemiology of somatoform disorders and other causes of unexplained medical symptoms

SECTION 5  psychiatry and medicine 998
disorders.(50) Some questionnaire studies ﬁ  nd prevalence rates as 
high as 5 per cent among university students.(51)
Conversion disorders
Limited epidemiological data are available concerning conversion-type somatoform disorders. As with other varieties of unexplained somatic symptoms, these disorders appear to be more common among women
(52) and are associated with increased prevalence of 
depressive and anxiety disorders.(53) Some evidence suggests that 
these conditions have declined in prevalence.(52) While many 
sources report that these conditions are more common in non-Western or developing countries, available epidemiological data do not necessarily support this view.
(9)

(9)
No systematic data are available regarding the epidemiology of factitious disorders. The available data include numerous case reports and a small number of case series—typically drawn from medical inpatient or medical specialty settings. Because the syn-drome is deﬁ  ned by deception, it is likely that a large proportion of 
cases go undetected.
Creed, F. and Barsky, A. (2004). A systematic review of the epidemiology of 
somatisation disorder and hypochondriasis. Journal of Psychosomatic 
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54, 352–8.Table 5.2.2.1  Summary of prevalence rates of speciﬁ  c somatoform 
disorders in community and primary care studies

Community 
studiesPrimary 
care studiesNotes
Somatization 
disorder1% 1–2% Diagnostic interviews 
probably under-count past 
symptoms, records reviews 
tend to ﬁ  nd higher rates
Multisomatoform 
disorder or 
subthreshold 
somatization5% 8–10% Less extreme form of 
somatization, but still 
strongly associated with 
disability and symptoms of depression and anxiety
Hypochondriasis 1% 1–5% Strongly associated with 
anxiety disorders
Persistent pain 
syndromes2–3% 15–20% Bi-directional relationship 
with depressive and anxiety disorders
Body dysmorphic 
disorder1% 1–5% Signiﬁ  cantly higher in 
certain medical settings (dermatology, cosmetic 
surgery) and in people with 

999
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27. Barsky, A., Wyshak, G., Klerman, G., et al. (1990). The prevalence 
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5.2.3 Somatization disorder 
and related disorders
Per Fink
The essential feature of somatization disorder and related disorders 
is that the patient presents multiple, medically unexplained symp-toms or functional somatic symptoms. These physical complaints are not consistent with the clinical picture of known, veriﬁ  able, 
conventionally deﬁ  ned diseases, and are unsupported by clinical or 
paraclinical ﬁ  ndings. The phenomenon of medically unexplained

paraclinical ﬁ  ndings. The phenomenon of medically unexplained 
symptoms cannot simply be classiﬁ  ed into one or a few diagnostic 
categories, but must be regarded as an expression of a basic mecha-nism by which people may respond to stressors as in the cases of depression and anxiety.
(1–3) Somatization disorder and related 
disorders must thus be considered to possess a spectrum of severity.
(3, 4) In this chapter, the focus will be on the chronic and 
multisymptomatic forms.
The somatization disorder diagnosis has its origin in the concept 
of hysteria. It was introduced in DSM-III in 1980 and was based on the criteria for ‘Briquet’s syndrome’ , a syndrome described in the early 1960s by Perley and Guze.
(5) They listed 59 physical and psy-

chological symptoms distributed in 10 groups: 25 of the symptoms from nine groups were required to qualify for the diagnosis of somatization disorder. All psychological symptoms were eliminated in the DSM-III modiﬁ  cation to avoid overlapping with 
other diagnoses.
The diagnostic criteria for DSM somatization disorder varied 
until the introduction of the current DSM-IV . The diagnosis was included in ICD-10 in 1992, but the ICD-10 criteria list different 5.2.3 somatization disorder and related disorders

SECTION 5  psychiatry and medicine 1000
symptoms, and require a different number of symptoms compared 
with the corresponding DSM criteria.
The somatization disorder diagnosis has been criticized for being 
too rigid for clinical use. Only the most severe cases with a speciﬁ  c 
predeﬁ  ned symptom proﬁ  le fulﬁ  l the diagnostic criteria, and the 
majority of those with multiple symptoms fall into one of the residual categories of ‘undifferentiated’ or ‘not otherwise speciﬁ  ed’ 
somatoform disorders.
(6)
T o increase the sensitivity, Escobar et al .(7) introduced an 
abridged somatization index. This required 4 symptoms for males and 6 symptoms for females out of the 37 somatic symptoms listed in the DSM-III, compared with 12 and 14 symptoms respectively for the full DSM-III somatization disorder diagnosis. Kroenke et al.
(8) have suggested a diagnosis of ‘multisomatoform disorder’ , 
deﬁ ned as three or more medically unexplained physical symptoms

deﬁ ned as three or more medically unexplained physical symptoms 
from a 15-symptom checklist along with at least a 2-year history of medically unexplained symptoms.
However, these abridged versions share the same basic problem 
as the original ones, namely that the chosen number of symptoms to qualify for the individual diagnoses is arbitrary and not  empirically based. Recently a new empirically based construct was introduced, and this may have solved the problem. This new ‘bodily distress disorder’ diagnosis is based on positive criteria and not solely on the exclusion of all organic possibilities.
(3)
(Table 5.2.3.1)
This chapter will not differentiate between the different subcate-
gories of somatoform and related disorders that are present along with somatic symptoms.Clinical features
Physical symptoms and complaints

Patients with somatization and related disorders may complain of any medically unexplained non-veriﬁ  able subjective physical 
symptoms, and the symptoms may refer to any part or system of the body.
Complaints can be divided into:
◆ Subjective symptoms , which are sensations and other complaints 
that cannot be veriﬁ  ed by another individual or by general 
methods of examination (e.g. pains and paraesthesia).
◆ Objective symptoms , which are complaints that can be veriﬁ  ed if 
present at the time of examination (e.g. haematuria, icterus, etc.).
Findings can be divided into:
◆ Provoked ﬁ  ndings , i.e. symptoms or signs (such as soreness result-
ing from pressure or sensory impairment), which the patient is unaware of until these are provoked during the physical examination
◆ Certain ﬁ  ndings , which include objective symptoms that are

◆ Certain ﬁ  ndings , which include objective symptoms that are 
veriﬁ  ed and phenomena unnoticed by the patient but found 
during the physical examination (such as an abdominal tumor)
The symptom complaints in patients with somatization disorder 
and related disorders are dominated by subjective symptoms and provoked findings, whereas objective symptoms and positive certain ﬁ  ndings and paraclinical ﬁ  ndings are unusual.
Subjective symptoms may be considered to be psychological

Subjective symptoms may be considered to be psychological 
phenomena arising from personal experiences, which others can-not judge or measure, despite the fact that these symptoms could be fully explained by the presence of organic pathology. This means that there are considerable inter-individual, cultural, and historical variations in the symptom presentation, which are determined by the patient’s life experience and sociocultural background, and the setting in which the patient is seen also plays a role.
(9) However, the 
patients may also present veriﬁ  able symptoms and signs due to a

patients may also present veriﬁ  able symptoms and signs due to a 
physical disease or defect, which they exaggerate and incorporate into their illness. Incidental inborn errors or degenerative changes, which are asymptomatic in most individuals, may tenuously be assigned clinical importance by the doctor or the patient. For instance, degenerative changes in the spinal column are seen in most individuals when they become older, and most do not have any pain, but a patient’s backache may be attributed to those changes. Furthermore, over time, the patient with a chronic condi-tion is likely to have undergone multiple tests, invasive procedures, operations, and received medications for treatment or diagnostic purposes, and this may cause not only iatrogenic harm but also physical complications.
(10) Finally, the patient may have a concur-
rent physical disease. The presented symptoms may thus be a difﬁ cult mixture of complaints of both organic and non-organic 
origin.

origin.
(11)
The patients typically complain of multiple physical symptoms ,
but the number of symptoms reported by the patients vary consid-erably from one patient to another and over time in the same individual. The patients may complain of multiple, medically unexplained symptoms in numerous bodily systems at presenta-tion, but sometimes the complaints are concentrated on one Table 5.2.3.1  Symptoms of and diagnostic criteria for bodily distress 
disorder
Yes No Symptom groups  
≥ 3 Cardiopulmonal/autonomic arousal 
Palpitations, heart pounding, precordial discomfort, 
breathlessness without exertion,  hyperventilation, hot or cold 
sweats, trembling or shaking, dry mouth, churning in stomach, ”butterﬂ  ies”, ﬂ  ushing or blushing 
≥ 3 Gastrointestinal arousal  
Frequent loose bowel movements, abdominal pains,

Frequent loose bowel movements, abdominal pains, 
feeling bloated, full of gas, distended, heavy in the stomach, regurgitations, constipation, nausea, vomiting, burning 
sensation in chest or epigastrium
≥ 3 Musculoskeletal tension
Pains in arms or legs, muscular aches or pains, feelings of paresis 
or localized weakness, back ache, pain moving from one place 
to another, unpleasant numbness or tingling sensations
≥ 3 General symptoms
Concentration difﬁ  culties, impairment of memory, feeling tired, 
headache, memory loss, dizziness
≥ 4 symptoms from one of the above groups 
Diagnostic criteria:
1–3:  ‘yes’: Moderate ‘bodily distress disorder’
4–5:  ‘yes’: Severe  ‘bodily distress disorder’

1001
symptom pattern at one time (e.g. a gastrointestinal illness) and on 
a different symptom pattern at another (e.g. a cardiopulmonary illness).
(11) This single-organ illness picture may be due to physi-
cians being inclined to focus their attention and investigation on the organ of their own specialty—especially in a multisymptomatic, complex patient, i.e. a gastroenterologist will focus on gastrointes-tinal symptoms and may ignore musculoskeletal symptoms. A new set of symptoms from another organ system may come to attention when diagnoses and treatment options have been ruled out for the current complaint. Iatrogenic factors may thus contrib-ute signiﬁ  cantly to the presented symptom pattern and changes in

symptom pattern. Patients with somatization disorder are often inconsistent historians. They may supply incorrect information about previous episodes of their illness, minimizing or ignoring earlier instances of illness and exclusively focusing on the current symptom pattern. This may be because the patients ﬁ  nd it difﬁ  cult 
to account for their complicated medical history, or because they 
do not want to confuse the doctor with what they believe is irrele-vant information. Therefore, the full clinical picture often only becomes evident after a full medical history has been obtained and the patient has been followed for some time.
Symptoms and ﬁ  ndings are not idiosyncratic but need clariﬁ  ca-
tion or speciﬁ  cation before becoming meaningful clinically. For 
instance, a patient complains of chest pain. There are multiple causes for chest pain, so for the doctor this is not very informative. A clariﬁ  cation or speciﬁ  cation is needed. A retrosternal-localized

pain of a pressing nature offers the doctor a very different diagnostic association than a chest pain that is described as being stabbing and located in the left side of the chest. In somatization disorder and related disorders, the patient usually presents a vague illness picturewith symptoms of non-speciﬁ  c  character and of low diagnostic 
value, i.e. symptoms that are common in the general population and which are found in many different mental and physical disor-ders (symptoms like fatigue, nausea, headache, dizziness).
The presentation of medically unexplained symptoms is atypical ,
that is to say the symptoms lie outside what is usual in an authentic physical disease.
(11) However, the patients may have ‘learned’ the 
typical symptom presentation from different sources. For example, a patient with atypical asthma-like attacks shared a room with a patient with genuine asthma during her third hospital stay; subse-quently, her attacks took on a more ‘authentic’ appearance.
(11)

(11)
Descriptions of symptoms are usually vague, imprecise, and incon-
sistent , and the patients often have difﬁ  culties giving further details 
about their illness and symptoms, i.e. describing the quality, inten-sity, and chronology. The symptoms are described as being of max-imum intensity all the time, but if the patients keep a diary of symptoms or if information is gathered from other sources like relatives or the family physician, a considerable variation in the sym-ptom intensity from day to day or from year to year often surfaces. The patients may have difﬁ  culties in the chronology of symptoms, 
mixing current and past symptoms and illness episodes in a disorganized and confusing manner. It is difﬁ  cult for the patients 
to identify relieving factors or behaviour and to identify triggering events or things that make them worse, or these are multiple, or vague and unspeciﬁ  c. This is in contrast to patients with physical

disease, who usually describe their symptoms in a consistent and 
precise manner (Table 5.2.3.2).
Typically, there is a marked discrepancy  between a patient’s 
subjective complaints and reports on his or her functioning when this is compared with the way the patient is observed to act, move 
Table 5.2.3.2 
Characteristic differences in symptom description and other characteristics of well-deﬁ  ned somatic and related disorders 
including functional somatic syndromes
Somatization disorder and related disorders Physical disease 
Symptom description
Location Vague, diffuse, alternating Well-deﬁ  ned, constant
Intensity Vague, indistinctly deﬁ  ned intensity, few variations, 
often at maximum at all timesWell-deﬁ  ned changes and levels of intensity
Periodicity Diffuse, difﬁ  cult to deﬁ  ne, are often denied Typically well-deﬁ  ned periods with aggravation or 
improvement

improvement 
Relieving or aggravating factors  Vague, indistinct, numerous Well-deﬁ  ned, fewNumber of symptoms Numerous, vague Few, well-deﬁ  ned, clearly describedThe nature of symptoms Unspeciﬁ  c Speciﬁ  cThe character of the symptoms Uncharacteristic CharacteristicIatropic symptoms and main complaints Vague, difﬁ  cult to identify Can be identiﬁ  ed and delimited from comorbid symptomsDescription Affective, emotional, interpreting Clear and descriptive
Other characteristics
Treatment and medication Difﬁ  cult to assess the effect, transitory Level of effect well-deﬁ  ned 
Previous treatment Unclear what treatment the patient has undergone. 
Diagnostic tests are often interpreted as treatmentThe patient can account for previous treatments
Emotionality Inadequate, e.g. exaggerated or marked unaffectedness

Emotionality Inadequate, e.g. exaggerated or marked unaffectedness 
( ‘la belle indifférence’)Adequate - empathic5.2.3 somatization disorder and related disorders

SECTION 5  psychiatry and medicine 1002
and perform during the examination, or compared with informa-
tion from other sources like family. For instance, the patient moves and sits completely freely despite complaining of severe back pain or gives detailed information despite complaints of severe memory impairment.
There may be emotional discrepancy  in which the patient shows a 
lack of concern about the nature and implications of the symptoms despite presenting severe symptoms that are threatening the patient’s future functioning and quality of life. Other patients may in turn be very affected and emotional in their description of the symptoms and illness, describing in a colourful, dramatic, and strikingly graphic manner.
The patient’s centre of attention is typically on the suffering, on 
the psychosocial consequences, and the restrictions that the symp-
toms impose on their life. On the contrary, patients with 
well-deﬁ  ned physical disease are concerned or worried about the

well-deﬁ  ned physical disease are concerned or worried about the 
implication of their disease for their future health, i.e. will they recover or will they die from the disease. This emotional or psycho-
social communication  among patients with somatization disorder 
may put pressure on the doctor to do something.
Patients with somatization disorder and related disorders usually 
attribute their symptoms to a physical disease, and in some cases they persistently may refuse to accept medical reassurance  despite 
appropriate medical evaluations. The ICD-10 criteria for somato-form disorders include this refusal to accept medical reassurance, but recent research indicates that many patients are unsure what is wrong with them, and they do not necessarily refuse non-medical explanations if they are presented in a meaningful and understand-able way.

(12) Although the patients may recognize that their physi-
cal symptoms are caused by, e.g. stressful events, this does not make the symptoms disappear, and they still need treatment. The weight of the symptom (refusing to accept medical reassurance) in the medical literature therefore seems out of proportion. However, in the most severe cases, patients may be involved in patient organiza-tions ﬁ  ghting for their illness to be recognized as an ‘authentic’ 
physical disease or ﬁ  ghting for a particular causality of their illness 
as, e.g. whiplash-associated disorder or hypersensitivity to electric-ity or chemicals (multiple chemical sensitivity). The patients may also ﬁ  ght for disability pension or ﬁ  nancial compensation. This is 
often more a question of getting their illness recognized than receiving ﬁ  nancial compensation. Some patients may be preoccu-
pied with the idea that they have been mistreated or neglected by

pied with the idea that they have been mistreated or neglected by 
doctors, and this group will often become involved in conﬂ  icts with 
doctors and in legal disputes.
In some cases, there is a sudden onset of the disorder in connec-
tion with a medical condition or a trauma in a previously normal and healthy individual. It could be a whiplash trauma, a fracture, an infection, or an acute intoxication. The symptoms persist despite the original disease being cured according to a biomedical or a sur-gical judgement. Instead, the illness worsens and more symptoms may emerge. Our knowledge about such disorders with abrupt onset is sparse.
Psychological symptoms and comorbidity
At examination, the patients may deny emotional symptoms or conﬂ  icts, and when they do report them, they often blame them on

At examination, the patients may deny emotional symptoms or conﬂ  icts, and when they do report them, they often blame them on 
their physical afﬂ  iction. Patients may also be reluctant to display 
emotional difﬁ  culties because of bad experiences of doing so. They may have experienced that doctors did not believe them or accused 
them of making up their symptoms and have consequently felt that their physical problems are not taken seriously. However, sooner or later, most patients will exhibit emotional difﬁ  culties, and if the 
patients feel understood by the physician, emotional problems may 
as well be presented. Patients may present many different types of emotional symptoms, often unspeciﬁ  c, but prominent anxiety

as well be presented. Patients may present many different types of emotional symptoms, often unspeciﬁ  c, but prominent anxiety 
and depressive symptoms are prevalent. Although the symptoms may be as marked as in affective and anxiety disorders, they are usually more transient, changing from one day to another and especially related to speciﬁ  c events. At times, the psychological 
symptoms may fulﬁ  l the criteria for a mood or anxiety disorder; 
but it is characteristic that the illness picture shows variations in both bodily and emotional symptoms.
Suicidal attempts are unusual but may occur especially among 
severe cases, but suicide is rare. Substance abuse is frequent, whether or not this is iatrogenic sanctioned.
The way the patients present themselves is inextricably linked 
to personal style and possible personality disorder. As a broad spectrum of personality disorders or traits
(13) is associated with

(13) is associated with 
somatization disorder, the presenting style varies greatly from one patient to another. Characteristically, three broad patterns of per-sonality style may be found in these patients, especially in chronic cases: dramatic–emotional type, paranoid–hostile type, and pas-sive–aggressive-dependent type. The same patient may show all three patterns. In less severe cases it is often observed clinically that the patients have previously been very active and hard working, have conformed socially, and had a strong social network with many responsibilities. The patients often display perfectionist traits and prefer to be in control of a situation.
Illness behaviour

Typically, patients with somatization disorder persistently exhibit consulting behaviour which results in an excessive use of medical services and alternative therapies. In chronic cases, they have often been subject to a large number of futile examinations, surgery, and medical/surgical attempts at treatment.
(10,14,15) However, some 
patients realize quite early in the illness course that the doctors cannot help them, or they are well managed by their family physician, so they do not necessarily display this consultation behaviour.
Due to negative results of medical check-up and treatment 
attempts and the patients’ persistent belief that they must have a physical disease, the patients may consult different physicians. The patients may have been, or may feel, mistreated or neglected by doctors and therefore want to get a second opinion, or they want to ﬁ nd a doctor who can help them. Sometimes this behaviour,

together with the patients’ personality, can result in disagreement 
and a mutual hostility between the patients and their doctors.
Furthermore, the different illness patterns at different times, 
combined with the patients’ seductive, demanding personality 
style, may result in disagreements between the different health 
care professionals involved in their care, which may complicate their care.
In chronic cases, all aspects of the patients’ social and family life 
may be centered around their illness, so that the whole of their family life is adjusted to the patients’ demands (‘illness as a way of living’).
(16)

1003
The diagnostic criteria for somatization disorder and related 
disorders have varied, with different permutations of the diagnostic terminology reﬂ  ecting difﬁ  culties in classiﬁ  cation and in establish-
ing valid criteria. The distinction between the individual somato-form disorders is unclear, which means that the majority of patients will exhibit clinical characteristics from different diag-nostic categories.
(6)
Except for hypochondriasis or health anxiety, the somatoform 
disorder categories are primarily based on the number or speciﬁ  city 
of bodily symptoms and on the duration of illness.(17) The 
disorders can be divided into acute and chronic forms, into a mul-tisymptomatic form, and into a form in which the patients only present few symptoms or symptoms mainly referring to a single organ system. The somatization disorder diagnosis includes the most chronic multisymptomatic cases lasting for 2 years or more.
The ICD-10 criteria require the following:

1 at least 2 years of multiple and variable physical symptoms for 
which no adequate physical explanation has been found;
2 persistent refusal to accept the advice or reassurance of several 
doctors that there is no physical explanation for the symptoms;
3 some degree of impairment of social and family function-
ing attributable to the nature of the symptoms and resulting behaviour.
The ICD-10 criteria require ‘multiple physical symptoms’ to 
include at least 6 out of 14 predeﬁ  ned symptoms, involving at least

include at least 6 out of 14 predeﬁ  ned symptoms, involving at least 
2 of the following: gastrointestinal, cardiovascular, urogenital, or skin or pain symptoms. In contrast, the DSM-IV criteria demand four pain symptoms, two gastrointestinal symptoms, one sexual symptom, and one pseudoneurological symptom that are not fully explained by a medical condition. No specific symptoms are listed, but examples are given. Consequently, there is only poor to moderate agreement between the DSM-IV and ICD-10 diagnostic criteria.
(16) Cases lasting less than 2 years are classiﬁ  ed as undiffer-
entiated somatization disorder. In ICD-10, multiple symptoms are required, which is not the case in DSM-IV .
Functional or somatoform diagnoses deﬁ  ned mainly by the 
number or speciﬁ  city of bodily symptoms include, besides somati-

zation disorder (F45.0 and 300.81), undifferentiated SD (F45.1 and 300.81), persistent somatoform pain disorder (F45.4 and 307.80), 
and somatoform disorder unspeciﬁ  ed/NOS (F45.9 and 300.82). 
In ICD-10, this also includes somatoform autonomic dysfunc-
tion.
(3–5) There may be reasons for also including neurasthenia 
(F48.0) into the group. The somatoform disorder concept has never 
been accepted among non-psychiatrists, which has led to the intro-
duction of many different functional somatic syndromes, e.g. chronic fatigue syndrome (CFS), ﬁ  bromyalgia, irritable bowel syn-
drome (IBS), and chronic benign pain syndrome, and new syn-dromes are intermittently introduced.
(18)
The newly introduced diagnosis of bodily distress syndrome

(18)
The newly introduced diagnosis of bodily distress syndrome 
or disorder may be a solution to this classification problem, although it has not yet been sufﬁ  ciently tested in daily clinical 
practice.
(3) The suggested diagnosis is based on an analysis of a 
large sample of patients from different medical settings, and it seems to encompass the various functional syndromes advanced by different medical specialties as well as somatization disorder and related diagnoses of the psychiatric classiﬁ  cation. The disorder 
may have different manifestations, i.e. GI, MS, or CP syndromes as shown in Table 5.2.3.1.
Diagnosis
A somatization disorder should be suspected in any individual with a vague or complicated medical history or unaccountable non-responsiveness to therapy. Patients with somatization disorder may not have or may deny emotional symptoms or conﬂ  icts, so

the absence of signiﬁ  cant emotional symptoms at the general psy-
chiatric interview and history taking will not exclude the diagnosis. But the presence of a previous or current emotional disturbance does support the diagnosis, as do previous episodes of medically unexplained bodily symptoms. Taken at face value, the physical symptoms are only of modest diagnostic importance, whereas unspeciﬁ  c or atypical symptoms in several bodily systems, or a very 
unusual presentation, speak in favour of the diagnosis. Multiple ﬂ uctuating symptoms of obscure origin, and their onset before the 
age of 30, strongly support the diagnosis. The diagnostic criteria displayed in Table 5.2.3.1 may be used, or the criteria listed in the DSM-IV or ICD-10 diagnostic criteria for somatoform disorders may be used.
Mental and somatoform disorders
In malingering , the patient feigns illness with a conscious motiva-
tion to avoid responsibility or to gain an advantage. In factitious

tion to avoid responsibility or to gain an advantage. In factitious 
disorder , the symptoms are intentionally produced and the patient 
may self-inﬂ  ict or induce diseases and lesions. In contrast to malin-
gering, there is no external incentive for producing the symptom(s), and the motive is unconscious and only understandable in a psy-chopathological context.
(19, 20) In somatoform disorders, both the 
symptom-producing behaviour and the motive are believed to be unconscious. However, factitious or malingering symptoms, mixed with other non-intentional symptoms, may occur in somatization disorder and related disorders.
(11)
Hypochondriasis or health anxiety  is mainly deﬁ  ned in cogni-

(11)
tive terms with the emphasis on a preoccupation with physical appearance or the fears of harbouring or developing a serious physical disease. The other categories of somatoform disorders put more emphasis on bodily symptoms. In dissociative or conversion 
disorder  the patients usually present fewer symptoms, but these 
are almost exclusively pseudoneurological symptoms. The onset is sudden, and closely associated in time with traumatic events, insoluble and intolerable problems, or disturbed relationships. The symptoms are transient and often remit suddenly after a few days, although they may persist for longer, but seldom for more than a few months. Episodes of dissociative or conversion disorders frequently occur in patients with other somatoform disorders.
In pain disorder , the predominating complaints are of medically 
unexplained pain in one or more anatomical sites. Various aches

unexplained pain in one or more anatomical sites. Various aches 
and pains are common in somatization disorder but are more ﬂ  uc-
tuating and not so dominating in the clinical presentation since they merge with other complaints.
In ICD-10 somatoform autonomic dysfunction , the patients 
complain of symptoms associated with a speciﬁ  c system or organ 5.2.3 somatization disorder and related disorders

SECTION 5  psychiatry and medicine 1004
that is largely or completely under autonomic innervation and 
control. For example, the patient refers the symptoms to the heart 
and cardiovascular system, the gastrointestinal tract, respiratory system, genitourinary system, etc.
In most other mental disorders  physical symptoms are promi-
nent; it is the rule, rather than the exception, that patients with 
mental disorders consult their family physician because of physi-cal and not emotional symptoms.
(2, 21)  The symptoms may be 
misinterpreted by the patient and the doctor as being caused by a physical disease. However, in these cases of ‘presenting’ or ‘faculta-tive’ somatizing, the patient will accept the diagnosis of a psychiat-ric disorder when it is established and will accept that the  symptoms are attributable to a psychic rather than a physical afﬂ iction.
(2)
Autonomic bodily symptoms are prominent in panic disorder

(2)
Autonomic bodily symptoms are prominent in panic disorder 
and generalized anxiety disorders, but the emotional component of the disorders is unmistakable and the patients will not, or only temporarily, attribute their symptoms to a physical disease.
In psychoses, particular schizophrenic physical symptoms and 
hypochondriacal belief are common. However, the complaints are of a paranoid quality and other psychotic symptoms are prom-inent, except in the case of hypochondriacal paranoia. Psychotic episodes may occur in somatization disorder, but these are usually transient.
(22)
In depressive disorders, the patient’s complaints are mood 
congruent, and the symptoms will disappear if the depression is treated. In a few cases, however, a depression may be expressed in mainly bodily complaints (i.e. masked depression), and if left untreated may result in a prolonged course.
In obsessive-compulsive disorder (OCD), the patient may fear

In obsessive-compulsive disorder (OCD), the patient may fear 
contracting a disease from an outside source (e.g. dirt, germs, viruses, etc.). The OCD disorders share many similarities with hypochondriasis, i.e. cognitive and emotional complaints are the main problem, whereas bodily symptoms seldom are dominating.
Medical conditions
The onset of multiple physical symptoms after the age of 40, in a previously physically and mentally healthy individual, suggests a general medical condition. However, multiple vague physical com-plaints may be prominent in mental disorders with late onset such as mood disorders, dementia, and withdrawal states.
Only a limited number of general medical conditions present 
vague, non-speciﬁ  c, and multiple somatic symptoms (e.g. hyper-

parathyroidism, hyperthyroidism, acute intermittent porphyria, myasthenia gravis, AIDS, multiple sclerosis, systemic lupus erythe-matosus, lyme disease, and connective tissues disease). In most of these medical conditions there will be positive paraclinical ﬁ ndings.
In genuine physical disorders, the key symptoms will usually be 
characteristic from one patient to another and across illness epi-
sodes. In contrast, the constellation of symptoms in somatization 
disorder and related disorders will usually be incompatible with any known, authentic physical disease, and the symptom picture will be of a more ﬂ  uctuating nature.
The prevalence of somatization disorder is about 1 per cent in the 
general population and 1 to 6 per cent in primary care and in  inpatient medical settings, but it is much higher if less restrictive,

general population and 1 to 6 per cent in primary care and in  inpatient medical settings, but it is much higher if less restrictive, 
abridged criteria are used.(3, 7, 8, 21, 23–28)  Both among primary care 
patients, newly referred neurological in and outpatients, and among internal medicine inpatients, the prevalence of severe bodily dis-tress disorder is 3.3 per cent, whereas the prevalence of modest bodily distress is 25.3 per cent.
(3) Regardless of the criteria used, 
females predominate with a male-to-female ratio of 1:2 to 1:6, and the prevalence is rather constant as to age.
(21, 24–29)
The age of onset is usually before 30 to 40 years.(14) This patient 
group poses a considerable ﬁ  nancial burden to health and social 
service provision, a loss to industry, and a dependence on invalidity beneﬁ  ts for long periods.
(14, 24, 30, 31)
Somatization disorder and related disorders are associated with a

Somatization disorder and related disorders are associated with a 
wide spectrum of heterogeneous psychiatric disorders, including personality disorders and mental retardation. The comorbidity rates are highest in the most chronic cases, in which rates of 50 per cent or higher are reported.
(3, 13, 22, 24) Cultural and ethnic 
factors may affect the prevalence rate. This may be due to the inﬂ uence of these factors on the likelihood of presentation to 
health care rather than real prevalence differences in the general population.
(7, 21, 23)  The typical presentation of physical complaints 
has varied throughout history and with the sociocultural environ-ment of the patient.
(32)
Aetiology

(32)
Aetiology
The aetiology of somatization disorder is unknown, but it is most likely multifactorial including biological, physiological, psychologi-cal, social, cultural, and iatrogenic factors. Different factors may have different importance at different times in the natural course of the illness. For instance, it may be a psychological trauma that precipitates the illness—but iatrogenic factors that maintain the illness. Whether the behavioural, cognitive, and other typical dis-turbances in somatization disorder and related disorders develop as a consequence of a basic biological defect in interaction with the patient’s life experiences, or vice versa, or whether the mentioned disturbances and other predisposing factors have an independent impact is, as yet, unresolved.
Viewing functional somatic symptoms as a common reaction

Viewing functional somatic symptoms as a common reaction 
of human beings to stressors, like in the case of depressed mood 
and anxiety, results in the conclusion that different unspeciﬁ  c pre-
disposing factors common for different mental disorders are involved.
(33) Relatively speciﬁ  c predisposing factors are physical or 
sexual abuse and parental complaints of poor physical health and medically unexplained symptoms during the patient’s childhood, whereas neither parental nor childhood well-deﬁ  ned physical ill-
nesses seem to be predisposing factors.
(34, 35)
The reported family transmission in somatization disorder may 
be due to sociocultural learning. However, there is some support for genetic transmission in somatization disorder, although twin studies have been inconclusive.
(36)

(36)
In the classical psychodynamic drive theory, medically unexplained physical symptoms are believed to develop as a reaction to the repression of unacceptable wishes or instinctual impulses and internal psychic conﬂ  icts.
(37)
According to the theory of self-psychology, the anxiety connected 
with a threatening defragmentation or disintegration of the self is

1005
the most profound form of anxiety that a person can experience.(37)
In a defence against the feeling of emptiness, the individual 
becomes directed on the outside world and on physical stimuli. This process has been called ‘stimulus entrapment’ meaning that in somatization disorder, the individual becomes addicted to stimuli to his or her body.
(38)
Individuals with alexithymia have a poorly developed language 
of emotions, and it has been suggested that instead they might respond with bodily symptoms. It is, however, unlikely that alexi-thymia has a speciﬁ  c aetiological role in somatization disorder.
The cognitive theory endorses the importance of the patients’ 
misinterpretation of benign symptoms and normal physical sensa-tions that they erroneously attribute to a physical disease.
(39)
Biological factors
It is beyond doubt that an important biological component is involved, although the speciﬁ  c nature has still to be discovered.

(39)
It is beyond doubt that an important biological component is involved, although the speciﬁ  c nature has still to be discovered. 
A neurophysiological dysfunction in the attention process has been demonstrated in somatization disorder, which may be explained by a reduced corticofugal inhibition in the diencephalon and the brainstem of afferent bodily stimuli, resulting in insufﬁ  cient ﬁ  lter-
ing of irrelevant bodily stimuli. A dysfunction of the secondary somatosensory area in the brain, a hypersensitivity of the limbic system towards bodily stimuli, or other dysfunctions may also be aetiologically involved.
(40–42)
Other factors
In a few cases, a simple compensation claim may be of aetiological importance.
Physicians are primarily trained in a biomedical illness model 
and may have insufﬁ  cient knowledge about diagnosing and man-

aging somatization disorder and related disorders. Physicians may thus have a tendency to pursue organic possibilities and feel com-pelled to evaluate and treat all symptoms, and consequently a con-siderable iatrogenic reinforcement of physical symptoms is often involved.
Somatization disorder and related disorders have a spectrum of severity ranging from cases that may be difﬁ  cult to delimit from 
normality to severely ill patients.
(17)
In severe cases, the patients are chronically ill for most of their

(17)
In severe cases, the patients are chronically ill for most of their 
lives, but there may be periods of partial, but seldom full, remis-sion. Some patients are able to work, others are severely disabled and are chair or bed bound, and their families have to provide vir-tually all aspects of physical care. Patients with somatization disor-der and related disorders are often subjectively more functionally handicapped than patients who have a comparable, yet fully explained medical condition.
(31)
The purposes of the initial assessment are to (a) establish the diag-nosis and rule out differential diagnoses, (b) examine which spe-ciﬁ c management or treatment strategies are possible and best for 
the patient, and (c) engage the patient in therapy.
(15)
A scheme for the initial assessment by the psychiatric specialist is

(15)
A scheme for the initial assessment by the psychiatric specialist is 
given in Table 5.2.3.3. For primary care physicians and in general hospitals this may be too comprehensive, and step one in the TERM 
model (Table 5.2.3.5) or another more simple model may be used.
(43)
Before meeting the patient
Before meeting the patient it is important to review medical case notes and to gather information from other sources, e.g. the pri-mary care physicians or the family, as patients with somatization disorder and related disorders may be inconsistent historians as a 
result of their complex medical history. The aim is to get an over-
view of the patient’s medical history, the illness picture and com-
plaints, examinations and diagnostic tests, and treatments and the 
outcome of these. It must also be assessed whether the patient is 
sufﬁ ciently examined for relevant differential diagnoses. The review

sufﬁ ciently examined for relevant differential diagnoses. The review 
may furthermore impart important information about psychologi-cal and social issues.
The examination
(a) Attitudes towards the referral and treatment

Patients with somatization disorder and related disorders may be sceptical about seeing a psychiatrist as they believe their problem to be of a physical nature and not psychiatric. This should be addressed directly by asking the patients what they have been told by the referring doctor, their reasons for coming to see the psychiatrist, and their feelings about it. It is important that such thoughts are brought to light to avoid misunderstandings and misconceptions, and to help the patients feel understood and in safe hands. In acknowledging the patients’ fears of being stigmatized, it may be helpful to discuss negative public attitudes to psychiatry.Table 5.2.3.3  Clinical assessment of patients with somatoform and 
related disorders including functional somatic syndromes
Before the meeting with the patient

Review medical records and other 
relevant material 
At the examination
Attitude towards the referral and the 
treatment 
Physical complaints Chronology, intensity, provoking / 
relieving factors etc.
Triggering factors Physical trauma or disease 
Psychosocial stressors
Current and previous emotional 
and behavioural complaints 
Social, funtional level, strain and 
coping
The patient’s illness belief and 
perception of symptoms
Expectations to treatment and 
investigation Physical
Psychiatric 
Past medical, surgical, and 
psychological history
DispositionsPhysical examination  Paraclinical tests: Obtain focused 
diagnostic tests if not already done5.2.3 somatization disorder and related disorders

SECTION 5  psychiatry and medicine 1006
(b) Current physical complaints
The patients’ physical complaints should be reviewed in detail for 
diagnostic purposes and to make the patients feel understood and taken seriously, which is a precondition for a good rapport between doctor and patient. Each symptom is explored to establish their characteristics, location, intensity, chronology and variation in 
intensity, onset, duration, and impact on daily life. Besides, provok-
ing/relieving factors, previous treatments and the outcome of these are explored. It may be helpful together with the patient to write down the medical history on a time axis as patients may have difﬁ  -
culties with the chronology of their illness.
(c) Triggering factors
It is explored if onset of the illness is associated with physical trau-ma or diseases or with exposure to psychosocial stress or trauma.
(d)  Current and previous emotional and behavioural 
complaints

As to a high comorbidity between somatization disorder and related 
disorders and other mental disorders, it is necessary to methodi-cally clarify if the patients have a depression, anxiety disorder, or another mental illness.
(e) Illness beliefs and perception of symptoms
The patients’ illness beliefs and perception of symptoms are of par-amount importance for their illness and functioning as the illness behaviour has its origin in those beliefs and in illness attitudes. T o change an inappropriate behaviour, it is necessary to identify such dysfunctional beliefs. Also, the attitudes and behaviour of the family may be a crucial factor in understanding the presentation and in planning the intervention.
(f) Expectations to treatments and investigations

The patients are questioned about wishes for and expectations to treatment and diagnostics tests and about what they believe may help them. Patients with somatization disorder and related disor-ders often have an unrealistic expectation to the impact of diagnos-tic tests and the effect of medical or surgical treatments. This may result in an intensive use of consultations. The patients must be helped to face the limits of what medicine can do and to acknowl-edge that continued medical consultations will be fruitless.
(g) Past medical, surgical, and psychological history
The patients’ history is reviewed and related to the information gathered during the medical case note review. Furthermore, it is attempted to elucidate the patients’ premorbid psyche and personality.
(h) Dispostions
Somatoform and related disorders often run in families and are associated with other mental disorders, and hence dispositions are explored.

(i) Physical examination
If not already made, a clinical examination ought to be carried out. Besides excluding organic possibilities, it also has a psychological purpose in making the patients feel that their physical complaints are taken seriously and that the psychiatrist is not exclusively focus-ing on the psychological part of the problem.
Routine laboratory test battery may be; complete blood count, 
electrolytes, blood urea nitrogen, creatinine, glucose, calcium, phosphate, liver function test, total protein, thyroid-stimulation hormone, erythrocyte sedimentation rate or CPR, urinalysis, and if 
indicated by symptoms or history, serological tests for Epstein–Barr virus, lyme disease, and immunological function test. Other tests may be relevant depending on the patient’s illness picture.
Feedback of the results

Feedback of the psychiatric examination results to the referring doctor must be done in a way that is intelligible to a doctor who may not be psychologically minded. Statements like ‘no formal psychiatric disorders are found’ , which unfortunately are frequent in consultation notes, may be somewhat useful when dealing with a patient referred for functional somatic symptoms. Such a state-ment just proves that the psychiatrist is unfamiliar with somatiza-tion disorder and related disorders.
The psychiatrist must be careful not to become involved in criti-
cism of medical colleagues and in the divisions that these patients sometimes try to create between different therapists.
Evidence-based treatment

Many different therapies have been used in patients with somatiza-tion disorder and related disorders like family therapy, physical therapy, biofeedback, relaxation therapies, hypnotherapy, psycho-dynamic psychotherapy, cognitive-behavioural therapy etc. The focus in the management varies a lot from (a) focus on the patients (organ-oriented approach or cognitive interpersonal approach, i.e. pattern of bodily and emotional symptoms over time, focus on dysfunction of central processing and context factors, interventions aimed at sensations, cognitions, affects, behaviours, and restoring overall function), (b) focus on the doctor (early recognition, com-munication skills, avoidance of iatrogenic harm), and (c) focus on context factors (doctor reimbursement system, patient compensa-tion schemes, health care system, workplace characteristics, cultural belief).
(44)
It must be concluded that the evidence for an effective  treatment

(44)
It must be concluded that the evidence for an effective  treatment 
of patients with multiple functional symptoms is unsystematic. The use of multiple treatment methods and outcome measure-ment makes it difﬁ  cult to compare studies. However, there seems 
to be substantial evidence that a specialized assessment with  discharge letter, CBT, brief psychodynamic psychotherapy, and  antidepressants have some effect on one or more outcome  parameters.
(44–47)
Treatment setting
Functional somatic symptoms and functional somatic syndromes are common in all medical settings. The patients often believe that they have a physical and not a psychological problem and will primarily seek medical and not psychological care. Hence, the management of somatization disorder and related disorders is not only an issue for psychiatrists but for all settings within the health care system.
The management must follow a stepped-care model, in which it is

The management must follow a stepped-care model, in which it is 
deﬁ ned at which level of specialization each patient should be treated 
and, for each step, who is responsible for which parts of the treatment. For example, the mild and uncomplicated cases are treated by the pri-mary care physician, modest to severe cases mainly by the primary care physician but in collaboration with a specialist, whereas the severe and complicated cases are managed in  specialized care.

1007
Besides the severity of the disorder, deﬁ  ning the steps in the model 
includes considerations about feasibility both as to available treat-
ment resources and what is acceptable to the patient and the skills and knowledge of the primary care physician. Patients with a chronic somatization disorder may be well cared for by their primary care physician, provided the latter has the necessary skills and knowledge.
Inpatient care may be appropriate in a few cases, but patients 
with somatization disorder and related disorders are difﬁ  cult to 
treat in ordinary psychiatric wards, where they are often met with considerable resistance from the psychiatric staff. Specialized inpa-tient units only exist in a few places in the world, and this treatment has not been documented.
Non-specialiszed treatment and management
(a)  General hospital departments and non-psychiatric 
specialists
Because of the prevalence and the risk of iatrogenic harm, it is

Because of the prevalence and the risk of iatrogenic harm, it is 
important that non-psychiatric specialists know about somatoform and related disorders and know how to identify and diagnose them. If the assessing physician exclusively focuses on symptoms that he ﬁ nds relevant for his own specialty, there is a great risk of pursuing 
a wrong diagnosis. The fear of overlooking a deﬁ  nite physical dis-
ease, as an explanation of the physical symptoms, is deeply rooted in doctors, and this may, together with a poor knowledge about somatoform disorders, result in the doctor attempting to rule out even the rarest physical causes before a somatization disorder is even considered. However, there is little evidence that important medical diagnoses are missed more often in patients with somato-form disorders than in patients with other disorders.
(48–50)

(48–50)
Unnecessary procedures and diagnostic tests are not only unpleas-ant and potentially risky for the patient but may also delay or hin-der sufﬁ  cient treatment resulting in an aggravation of the disorder 
or perhaps chronicity. However, it must always be borne in mind that patients with a somatoform disorder may also have or acquire a concurrent physical disease. Instead of viewing somatization disorder and related disorders as a diagnosis of exclusion, all diag-nostic possibilities ought to be included in the diagnostic consider-ation and the examination plan from the initial contact in the same way as when it is a question about two well-deﬁ  ned organic 
diseases. Diagnostic tests should be on medical indication and not on patient demand.
The primary role of the non-psychiatric specialists in the treat-
ment of somatization disorder and related disorders is to:
◆ Exclude physical disease or trauma that can be treated medically 
or surgically

◆ In an empathic way, make it clear to the patient that he or she 
does not have the physical disease he or she fears, and that there 
is no indication of any other physical disease or defect that needs 
medical attention.
◆ That there is no medical indication for further diagnostic tests or 
examinations
◆ Coordinate the management with the primary care physician 
and other doctors that the patient may be in contact with.
◆ Consider a referral to a psychiatrist for examination or 
 treatment
◆ In chronic cases, follow the advice given in Table 5.2.3.4.As previously mentioned, patients with somatization disorder

 treatment
◆ In chronic cases, follow the advice given in Table 5.2.3.4.As previously mentioned, patients with somatization disorder 
are often resistant to psychiatric referral as they believe they have a physical and not a psychological problem. They may construe the referral as a sign that the physicians are not taking their symptoms seriously. It is important that the referring physicians avoid giving the message that the patients are not genuinely ill, that they trouble the doctors unnecessarily, or that they are ‘mad’ .
(51) Instead, the Table 5.2.3.4  General advice on the non-specialized management of 
chronic somatization
Physical
 1. Make a brief physical examination focusing on the organ system from 
which the patient has (new) complaints.- Look for signs of disease instead of symptoms.
- Avoid tests and procedures unless indicated by signs of disease or a 
well-deﬁ  ned (new) clinical illness picture.

well-deﬁ  ned (new) clinical illness picture. 
 2. Reduce unnecessary drugs. Do not use on demand prescriptions and 
avoid dependence-forming medication. 
Psychological
 3. Make the diagnosis and inform the patient that the disorder is known 
and has a name.
 4. Acknowledge the reality of the symptoms.
 5. Be direct and honest with the patient about the areas you agree on, 
those you do not agree on, but be careful as not to make the patient feel 
ignorant or not respected.
 6. Be stoical; do not expect rapid change or cure.
 7. Reduce expectations of cure and accept the patient as being chronically 
ill. Aim at containment and (iatrogenic) damage limitation, i.e. use the 
management rather than treatment. 
 8. Perceive worsening of/or new symptoms as emotional communication 
rather than as a manifestation of a new disease.  
 9. Apply a speciﬁ  c therapeutic technique if you master it and consider

8. Perceive worsening of/or new symptoms as emotional communication 
 9. Apply a speciﬁ  c therapeutic technique if you master it and consider 
referral to specialist treatment. 
Psychopharmacological treatment 
10. Consider treatment with psychoactive mediation (primarily 
antidepressant).
11. Choose non-habit forming medication and, if possible, choose 
medication that can be serum monitored.
12. Start with a smaller dosage than usual and increase slowly. Be stoical 
about side effects. 
13. Take regular serum values to compliance issued and for validating 
complaints of adverse effects. 
14. Treat any co-existing psychiatric disorders according to usual guidelines.
Administrative
15. Be proactive rather than reactive. Agree on a course with ﬁ  xed, scheduled 
appointments with 2–6-weeks intervals and avoid consultations on patient demand (if needed, accept on demand a maximum of 1 phone 
appointment per week).

16. If the patient has a job, avoid giving him sick leave if at all possible. 
17. Try to become the patient’s only physician and minimize the patient’s 
contact to other health care professionals, doctors on call, and alternative 
therapists. 
18. Inform your colleagues of your management plans and develop 
contingency plans for when you are not accessible. 
19. Inform the patient’s nearest relative and try to co-opt a relative as a 
therapeutic ally. 
20. If necessary, arrange support/supervision for yourself. 
21. If necessary, motivate the patient to receive psychiatric treatment. 5.2.3 somatization disorder and related disorders

SECTION 5  psychiatry and medicine 1008
physician must try to meet the patients’ wishes about knowing the 
cause of their illness, being taken seriously, getting explanations, information, advice, and reassurance.
(52) A close liaison with medi-
cal colleagues guiding them in making a psychiatric referral in an acceptable way is important for engaging the patient in treatment.
Primary care
The TERM model (the extend reattribution model) is a simple cognitive-behavioural orientated treatment method to improve the primary care physicians’ detection and management of patients presenting with medically unexplained symptoms. The method can effectively be taught to primary care physicians and will improve the outcome of their patients’ treatment.
(43) The TERM 
model is one of several different models that have been developed on the basis of the original reattribution model.
(53,54)
The ﬁ  rst stage of the TERM model (Table 5.2.3.5) is called

(53,54)
The ﬁ  rst stage of the TERM model (Table 5.2.3.5) is called 
‘understanding’ , as the important point, besides assessment of the patient, is that the patient feels understood and taken seriously by the doctor. The second stage is called ‘the physician’s expertise and acknowledgement of illness’ , in which the physician feeds back the results of his examination, but at the same time acknowledges the reality of the symptoms. The third stage is called ‘reframing’ , in which a new model of understanding of the patient’s problem is negotiated between patient and doctor. As a fourth stage, the model includes techniques for negotiating further treatment.
(43)
Finally, the model includes principles for management of chronic,

(43)
Finally, the model includes principles for management of chronic, 
somatizing patients (Table 5.2.3.4). In chronic cases, damage limi-tation is a more realistic therapeutic goal than cure, and manage-ment is thus a more realistic aim than treatment.
(51, 55, 56) The main 
aim is to stop the pathological cycle of interventions and consulta-tions and the consequential somatic ‘overtreatment’ (i.e. treatment on obscure indication), and then, if possible, gradually to motivate the patient to accept specialized care if available in the area. Management according to these principles has shown to be effec-tive in randomized controlled studies and should therefore always be implemented either solely or combined with one of the treat-ments described below.
(57)
Specialized treatment and management

(57)
Cognitive-behavioural therapy is the best documented and most widely used therapy and is hence the focus in this section along with pharmacotherapy. The general principles of CBT are described elsewhere, so this section concentrates on the general techniques used in somatization disorder and related disorders, and how they differ from the CBT techniques applied in other disorders.
(a) Goal setting
Early in the therapy, the goals for the therapy are established. It is important to set up goals that are realistic in the light of the patient’s illness and the framework of the therapy.
(b) Engagement and motivation

Treatment of somatization disorder and related disorders differs from the treatment of other mental disorders on several points, one being that it is very important to work systematically by engaging the patients in therapy. As the patients believe they have a medical condition, they may have very low belief in psychological treat-ment. It may be helpful to discuss the idea that all illnesses have an emotional component and that a psychological treatment focusing on the emotional component is often helpful in reducing suffering. 
The motivation and engagement should preferably be established during the assessment interview.
(c) Psychoeducation

The patient needs to be taught about somatoform and related dis-orders and about the body’s normal reactions to stress and how stress may be expressed in physical symptoms. It is important that the patient learns about the possible biological and physiological basis in the CNS for the symptoms. This will make the reality of the symptoms clear to the patient and emphasize that the illness is not imaginary or made up. The education may be supported by written information. Parts of the information ought to be repeated during the therapy when it, in a relevant way, can be linked to the patient’s personal experience.Table 5.2.3.5 The TERM model
1.  Understanding
 Take a full history of the symptoms
 Explore emotional clues
 Inquire directly about symptoms of anxiety and depression
 Explore life events, stress, and other external factors Explore functional level

Explore emotional clues
 Explore the patient’s health beliefs
 Explore the patient’s expectations to treatment
 Make a brief, focused physical examination 
2.  The physician’s expertise and acknowledgement of illness
 Provide feedback on the results of the physical examination
 Acknowledge the reality of the symptoms
  Make it clear that there is no (or that there is indeed) indication for further 
examination of nonpsychiatric treatment
3.  Negotiating a new model of understanding (reframing)
 Simple explanations
   Physical symptoms are common reactions to, for example, stress and 
strain/nervousness
  Depression lowers the threshold of pain
  Muscular tension in anxiety and nervousness causes pain
 Demonstrations
  Practical (hyperventilation, muscular tension)
   Establish the association between physical discomfort, emotional

Muscular tension in anxiety and nervousness causes pain
   Establish the association between physical discomfort, emotional 
reactions, and life events
  “Here and now” (nervous about consulting the physician)
 Severe cases
  Known phenomenon with a name: somatization
   Basically the cause is unknown, but nothing indicates a hidden physical 
disease
   Biological explanation: some are bodily sensitive than others, which 
explains their more intense symptoms
   Individual symptom coping and reactions determine one’s future well-
being
4.  Negotiating further treatment
 Sum up agreements made during the consultation
 Agree on speciﬁ  c objectives, contents, and form for the future course
 Acute cases: no further appointments Subacute cases: therapy sessions, regular scheduled appointments 
 Chronic: consider status consultation, regular scheduled appointments

Acute cases: no further appointments Subacute cases: therapy sessions, regular scheduled appointments 
 Consider referral to psychiatrist, psychologist, or specialist service 
5.  Chronic cases
 See Table 5.2.3.4

1009
(d) Physical symptoms and symptom attribution
Figure 5.2.3.1 illustrates the relationship between symptoms, cog-
nitions, emotions, and behaviour in the cognitive-behavioural model. The ﬁ  rst step in the therapy is to clarify the patient’s dysfunc-
tional automatic thoughts and basic beliefs about illness and symptoms, i.e. cause, consequences for future health and function, treatment, etc. Those thoughts are related to feelings and illness behaviour.
In the next step, the patient’s disease model and symptom attri-
butions are challenged. The therapist asks the patient to consider alternative possibilities, in which process even the most unlikely explanations are welcome. The therapist and the patient then explore which explanation is the most likely by investigating pros and cons for each possible explanation.
Finally, it is clariﬁ  ed how the patient would behave and react to a 
particular understanding or belief and which feelings this would 
produce.
(e) Behaviour and coping

produce.
Even if the patient does not want to or cannot work with his or her illness perception and symptom attribution, it would still be possible to work with the way the patient copes with illness. Illness behaviour and coping with symptoms and illness are scrutinized, and the behaviour is linked to the underlying thoughts and feelings if possible. When an example of a behaviour or coping strategy is elucidated, it is listed with arguments for and against a particular behaviour or coping strategy. A brainstorm on alternative possi bilities is advisable, and pros and cons for each of these are also scrutinized. In a negotiation with the therapist, the patient chooses an alternative possibility, which is tested by the patient as homework, and at next session the effect of this is explored.

It is important to go slowly for the patient to experience success. 
The therapist is obliged to make sure that the patient sets up realistic goals with a good chance of success.
(f) Links between symptoms and stressors
The cause of somatization disorder and related disorder may be viewed as a combination of personal vulnerability and the stress and strain an individual is exposed to. The patients are often unaware of their patterns of reaction, but this can be established by 
careful registration of variations in symptom intensity and then relating them to what the patients are doing or thinking at that time. Based on variation in symptom intensity and stressors, potential important stressors in everyday life may be identiﬁ  ed. 
This may provide a focus for intervention.
(g) Family and social network

The patient’s health beliefs are often shared with the family and social network. Therefore it is necessary to create an alliance with the family to make sure they support the patient and not counter-act the therapy. Family members are invited to a consultation and informed about the nature of the disorder and about the planned treatment. Misunderstandings and prejudgements about somatiza-tion disorder are eliminated.
(h)  Treatment and help seeking behaviour and the 
physicians’ handling
For patients with somatization disorder, social and family life is

For patients with somatization disorder, social and family life is 
often centered on their illness, and an objective of the therapy is to reduce the importance of the illness and try to build up other inter-ests and aspects of life. The patient’s consulting behaviour may result in multiple fruitless diagnostic tests, referrals, and treatment attempts, which expose the patient to iatrogenic harm. Often, the patient grows tired of the doctors responding to their questions merely by referring or prescribing medication. In therapy, the patients are taught how to present their problems to the physicians in a way that prevents referrals and medication.
(58) A patient may

(58) A patient may 
for instance tell the doctor that he or she is worried about some new symptoms, because he or she does not know whether the symptoms are just part of his or her somatoform disorder or some-thing else, and that the doctor’s expertise is required in order to clarify this.
Coexisting mood, anxiety, or other mental disorders are as effec-tively treated with psychotropic medication in patients with a somatoform disorder as in patients without.
(59) Patients without 
coexisting mental disorders also seem to beneﬁ  t from psychophar-
macological treatment, antidepressants being the ﬁ  rst choice.(44) In 
some cases, medication with peripheral action may be helpful as symptomatic treatment, for example in case of gastrointestinal symptoms like IBS.
(44) Tricyclic antidepressants seem most effec-
tive, but due to side effects SSRI or SNRI ought to be the ﬁ  rst

tive, but due to side effects SSRI or SNRI ought to be the ﬁ  rst 
choice. A useful strategy in the psychopharmacological treatment of somatizing patients is to start on a lower dosage than is usually recommended and to increase the dosage only gradually in order to avoid side effects. Antidepressants with the fewest interactions should be chosen as polypharmacy is common in these patients. The use of benzodiazepines and other dependence-producing drugs should be avoided. Stronger painkillers usually only produce a partial and temporary improvement, but they may result in mis-use and should be avoided. Mild painkillers and tricyclic antide-pressants are to be preferred.
In general, a degree of stoicism is required on the part of the 
clinician as patients may have varying symptom intensity and motivation and because patients may complain of side effects as a 
result of increased sensitivity to bodily sensations. Drugs that can

result of increased sensitivity to bodily sensations. Drugs that can 
be serum-monitored are preferred so that compliance and the like-lihood of side effects can be assessed.Fig. 5.2.3.1 Basic model in cognitive behavioural therapy.Physical symptoms / sensations
Cognitions Behaviour
Emotions5.2.3 somatization disorder and related disorders

SECTION 5  psychiatry and medicine 1010
Patients with medically unexplained symptoms are often unpopu-
lar both with general psychiatrists and other doctors. The patients are seen as neither physically nor mentally ill, but simply as indi-viduals complaining in order to avoid normal life responsibilities. Overcoming these negative attitudes is a matter of proper training of doctors and education of medical students.
Since an early diagnosis is important for preventing physical ﬁ  x-
ation, iatrogenic harm, and chronicity, doctors must be taught to view somatization disorder and related disorders with the same seriousness as well-deﬁ  ned physical diseases. The dominating dual-
istic way of thinking in medicine must be counteracted.
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5.2.4 Conversion and 
dissociation disorders
Of all the disorders characterized by symptoms in the absence 
of disease, conversion disorders are perhaps the most difﬁ  cult

of disease, conversion disorders are perhaps the most difﬁ  cult 
to explain. How, for example, can one explain functional blindness or a loss of function of both legs in the absence of conspicuous organic disease? The ancient Greeks recognized that if we suffer emotional disturbance as a result of some serious stress (such as personal injury or bereavement), this causes a change in the nervous system which leads in turn to symptoms in different parts of the body according to the underlying pathophysiology. Nineteenth century neurologists made signiﬁ  cant advances when they identi-
ﬁ ed speciﬁ  c ideas at the root of the symptoms. In the early nine-
teenth century Collie
(1) also observed that the signiﬁ  cance of,

(1) also observed that the signiﬁ  cance of, 
and attention to, a symptom or set of symptoms may depend more on what they mean (or their value) to the individual than on the biological underpinnings of the symptom itself.
Spence has recently argued that the problem in hysterical motor 
disorders is not the voluntary motor system per se : rather, it is in 
the way that the motor system is utilized in the performance (or non-performance) of certain willed, chosen, actions .
(2) This model invokes

(2) This model invokes 
a consciousness that acts upon the body and the world. By contrast, the psychodynamic (‘conversion’) model, which Freud introduced and which held sway for most of the twentieth century, invokes an unconscious mechanism ‘acting’ independently of consciousness, to interfere with voluntary movement. Spence has further argued that hysterical paralyses are maintained not by unconscious mech-anisms, but by conscious processes. The maintenance of these symptoms requires the patient’s attention, a characteristic of higher motor acts; the paralyses break down when the subject is distracted, 
consciousness is obtunded, or when it (the ‘paralyses’) is circum-
vented by reﬂ  exive motor routines. Hysterical paralyses, Spence

vented by reﬂ  exive motor routines. Hysterical paralyses, Spence 
avers, are quintessentially disorders of action (or inactions), which the patient disavows, when faced with some overwhelming situation, which threatens the identity of the self.
(2)5.2.4 conversion and dissociation disorders

SECTION 5  psychiatry and medicine 1012
One regrettable development of psychiatry’s adoption of 
Freudian theory was the fracture in communication between the disciplines of psychiatry and neurology, which has only recently been restored by the sort of collaborative research currently being carried out by neurologists and psychiatrists.
(3) In the last decade 
there have also been exciting advances in neuroimaging, which have stimulated research into the neurophysiology of hysteria, and these will be described later. This chapter will also emphasize contemporary approaches to management of these difﬁ  cult clinical 
problems.
Problems with deﬁ  nition
There are a number of problems with the deﬁ  nition of the conver-
sion disorders (CD). First, physical disorder must be excluded, but neurological co-morbidity is known to be high in patients with CD,
(4) and distinguishing which symptoms are accounted for by 
organic disease and which are not can be difﬁ  cult. Second, it is stat-

ed that a temporal association between a psychological stressor and the onset on the disorder should be identiﬁ  ed, but in practice this is 
often impossible to establish and depends to a large extent on the skill of the interviewing doctor. Finally, by deﬁ  nition (according to 
the glossaries ICD-10 and DSM-IV)
(5, 6); the process should be 
unconsciously mediated, but it is difﬁ  cult (some would say impos-
sible) to distinguish between symptoms that are not consciously produced and those that are intentionally manufactured. The DSM-IV provides no criteria to distinguish conscious from uncon-scious intent, and many authors have argued that the criteria for whether the patients are consciously aware of producing these symptoms should be dropped from the diagnosis of CD.
(7)
In clinical practice it is often difﬁ  cult for a physician, faced with a

(7)
In clinical practice it is often difﬁ  cult for a physician, faced with a 
patient in a hospital bed unable to use his or her legs despite normal tests and clinical ﬁ  ndings, to differentiate between conversion disor-
der, factitious or fabricated disorder, or frank malingering. Whatthe clinician is being asked to do is to determine whether or not the symptoms are being produced intentionally or not; and what the motives are. Table 5.2.4.1 attempts to provide a framework, but it highlights the shortcomings of psychiatric glossaries, which in turn expose the limitations of the medical model, which forces doctors to place patients in categories without taking into account the normal moral capacity of many individuals to exercise choice and deter-mine (at least to some extent) their actions.
(8) These medical 
 conundrums have been explored in more detail in the chapter on factitious disorders and malingering (Chapter 5.2.9).
The role of volition

Central to recent debates about hysteria and conversion disorders is the extent to which a person’s illness presentation is considered a product of free will and hence social deviance or the result of psy-chopathology and/or psychosocial inﬂ  uences beyond the volitional 
control of the subject.
(9) The proposal that voluntary processes are 
involved in some way has a very long history: something prevents a speciﬁ  c voluntary behaviour from being executed through a 
‘negative’ , lack of movement (as in paralysis), or a ‘positive’ , abnor-mality of movement (as in psychogenic tremor). If ‘will’ is regarded as a conscious capacity that humans possess to choose what to do or refrain from doing, then the problem in CD appears to be that the will fails to produce normal action.

(10) Hence, the diagnostic importance is placed on the patient’s veracity: if we believe him 
when he says that he cannot act normally we conclude that his will is impeded pathologically; if we do not believe him we conclude instead that his will is deployed to deceive us. This is the distinction required by the diagnostic systems.
Conversion and dissociation
The word conversion is conventionally applied to somatic symptoms 
whereas if the symptom is psychological (e.g. a loss of memory or an external hallucination) rather than bodily (e.g. a loss of power) it is regarded as dissociative. Dissociation  has attracted considerable 
recent interest, and it has been argued that the available evidence is more consistent with a model that identiﬁ  es at least two distinct 
categories of dissociative phenomena—‘detachment’ and ‘com-partmentalization’—that have different deﬁ  nitions, mechanisms, 
and treatment implications.
(11) These have been referred to as

(11) These have been referred to as 
Type 1 (compartmentalization) and Type 2 (detachment), respec-tively (see Table 5.2.4.2).
Compartmentalization phenomena  are characterized by impair-
ment in the ability to control processes or actions that would usually be amenable to such control and which are otherwise functioning normally. This category encompasses unexplained neurological symptoms (including dissociative amnesia) and benign phenomena such as those produced by hypnotic sugges-tion. By contrast, detachment phenomena  are characterized by 
an altered state of consciousness associated with a sense of separa-tion from the self, the body, or the world. Depersonalization, derealization and out-of-body experiences constitute archetypal examples of detachment in this account. Evidence suggests that

these phenomena are generated by a common pathophysiological 
mechanism involving the top-down inhibition of limbic emotional processing by frontal brain systems. Although these two types of dissociation are typically conﬂ  ated, evidence suggests that different 
pathological mechanisms may be operating in each case.Table 5.2.4.1 Relationships between conversion hysteria, factious 
disorder, and malingering
Subject insight Target of 
deceptionPerceived 
outcomeMotivation/
reason
Aware Unaware Conscious 
selfOther
Hysterical 
conversion++ Sick and 
disabled 
role Care/
dependency
Factious 
disorder++ Sick and 
disabled 
roleCare/
Malingering ++ Sick and 
disabled rolePersonal 
beneﬁ  t, e.g. ﬁ  nancial, 
avoiding 
prison
(Reproduced from Halligan, P . Bass, C. and Oakley, D. Wilful deception as illness behaviour. 
In Malingering and illness deception  (eds. P . Halligan, C. Bass, and D. Oakley), pp. 3–28. 
Copyright 2003, with permission from Oxford University Press).

1013
Support for the compartmentalization model comes from psy-
chophysiological research, which suggests that psychogenic illness is associated with a deﬁ  cit in attentional, conscious processing and 
the preservation of preattentive, preconscious processes. According to Brown
(12) there is very little difference between ‘negative’ 
symptoms such as sensory loss, paralysis, etc. and ‘positive’ symp-toms such as tremor, dystonia, etc. in terms of basic underlying mechanisms. By this view, all symptoms result from a loss of normal high-level attentional control over low-level processing systems; in this sense, all symptoms can be thought of as involving a form of compartmentalization.
There has been considerable progress in cognitive neuroscience and functional imaging over the last decade, which has provided a conceptual and empirically based platform for developing a neuro-science of not only hysterical symptoms but also free will.

(13,14)Recent functional neuroimaging data suggest that neural circuits 
linking volition, movement, and perception are disrupted in CD.(13)
There are many studies examining the role of speciﬁ  c prefrontal 
regions in action generation (particularly the dorsolateral prefron-tal and supplementary motor areas) and action suppression (espe-cially the orbitofrontal cortices). These ‘higher’ executive centres supervene only when a change of behaviour is required: inappro-priate behaviour must be suppressed or difﬁ  cult procedures attend-
ed to, as when concentration is necessary. Hence, if the problem in hysteria is one of the will, and of abnormality emerging only when subjects attend to their actions, then this suggests the hypothesis that the prefrontal cortex is pivotal to the conversion process (see Fig. 5.2.4.1).
Further evidence that the prefrontal cortices play a key role in

Further evidence that the prefrontal cortices play a key role in 
the control of action comes from a study of a woman with a left-sided conversion disorder affecting her leg. Marshall et al .
(15)
demonstrated that her attempt to move her paralysed leg was asso-
ciated with increased activation of orbitofrontal (inhibitory) pre-frontal regions, in the absence of motor cortical activity. They argued for an inhibition of motor behaviour by higher centres. Spence and colleagues
(16) demonstrated that in three men with

(16) demonstrated that in three men with 
conversion symptoms affecting their upper limbs, hypokinetic movement was associated with reduced activation of dorsolateral (action-generation) areas of prefrontal cortex. Moreover, these areas of hypoactivity differed from those exhibited by four healthy men who were asked to feign the same motor impairments (see Fig. 5.2.4.2). It is possible that the application of functional neuro-imaging techniques might allow clinicians to distinguish conver-sion from feigning on objective, empirical grounds.Table 5.2.4.2  Classiﬁ  cation of two types of pathological dissociation
Type 1 dissociation 
(compartmentalisation)Type 2 dissociation (detachment)
Conversion disorders Depersonalization/derealization
Dissociative amnesia Peri-traumatic dissociation
Dissociative fugue Out of body experiencesDissociative identity disorder Autoscopy (?)
(Reproduced with permission, from R. Brown (2002))5.2.4 conversion and dissociation disorders

Fig. 5.2.4.1 Schematic diagram illustrating the role of prefrontal executive in modulating lower motor systems, and its hypothesized involve ment
in conversion disorder. (Reproduced with permission from Spence, S. (2006). Hysteria: a new look. In  Psychiatry , 5(2), pp. 56–60, Elsevier Ltd.)

SECTION 5  psychiatry and medicine 1014
In another recent case report using fMRI a patient with right-
sided paralysis was asked to recall traumatic memories using a standard life event schedule: cued recall of the event was associated with regional brain activities characteristic of emotional arousal, including the amygdala and right inferior frontal lobe. Such recall was also associated with reduced motor activity in the area corre-sponding to the subjective paralysed limb.
(17) This case study pro-
vides neuroimaging evidence for a connection between traumatic events and ongoing neurological symptoms (see Problems with deﬁ nition, above).
It is ironic that these research advances have occurred at a time 
when social historians have conﬁ  dently asserted that hysteria has 
disappeared from clinical practice:
The most consequential development in the history of hysteria in

The most consequential development in the history of hysteria in 
the last century was the rapid decline in the medically recorded inci-dence of the disorder . . . . . . . .Hysteria—considered variously as a term, a theory, and a behaviour—is vanishing .
(18)
It is extraordinary that this was written in 2001, at a time
when symptoms considered ‘functional, psychogenic, medically unexplained or hysterical’ account for up to a third of new referrals 
to neurology outpatient departments.(3) and up to 9 per cent of 
admissions to a UK neurology in patient ward.(19) Akagi and 
House(20) concluded that the lowest prevalence ﬁ  gures suggested a 
rate of about 50 per 100 000 for cases of CD known to health ser-vices at any one time, with perhaps twice that number affected over a 1-year period. These ﬁ  gures suggest that hysteria is as common as

other disabling conditions such as multiple sclerosis and schizo-phrenia. Furthermore, the burden of disability associated with chronic hysteria is far higher than a typical practising psychiatrist might expect, or than is reﬂ  ected in standard textbooks of psychia-
try or clinical neurology.
(21)
It is regrettable therefore that it receives none of the resources or 
media attention that these disorders attract.
Conversion disorder: motor symptoms
The most typical motor symptoms are paralyses, functional weak-ness, gait disturbances, ﬁ  ts resembling epilepsy, and abnormal 
movements.
In the last decade diagnostic procedures have improved and the 
availability of non-invasive, accurate imaging has drastically reduced the rates of undetected organic pathology in patients with diagnoses of hysteria. Indeed, several recent studies have reported rates of misdiagnosis of between 0 and 4 per cent in regional and tertiary neurological centres,

(22) which suggests that a diagnosis 
of CD can be made relatively conﬁ  dently and accurately. In the 
following section the process of diagnosis will be brieﬂ  y outlined 
through the history, examination, and investigation.
(a) The history
The onset, temporal sequence, and character of the presenting complaint may not be typical of a neurological disorder, and a number of other features may emerge, especially after an interview with a family member or a review of the hospital and general prac-titioner notes. If the patient is admitted to a general hospital bed the psychiatrist should routinely telephone the patient’s primary care doctor and request a recent print out of his/her medical records (with consent). These often reveal key information about life events and/or antecedent illnesses, investigations, etc.
(i) Age of onset and sex
The average age of onset is the mid-30s, and patients with func-tional paralysis are less likely to be female than patients with pseu-do seizures.

(ii) Mode of onset/recent life events or difﬁ  culties
An increased number of life events in the year preceding symptom onset have been recorded in small controlled studies of unexplained motor symptoms
(23,24) . When patients are interviewed carefully, 
some report symptoms of panic just before the onset of, for exam-ple, functional weakness.
(25) Judicious questions about sensations 
of sweating, dizziness, and difﬁ  culty breathing may reveal these 
somatic symptoms of anxiety, which may also be reported before the onset of sensory symptoms (see below). There is also an impor-tant literature describing unilateral somatic symptoms (which may present with sudden onset of functional weakness in a limb) fol-lowing hyperventilation/panic.
(26,27)  These patients may present

(26,27)  These patients may present 
acutely in the A and E department of a general hospital, where they Fig. 5.2.4.2 Image showing regions where those with conversion disorder 
exhibited hypofunction during hypokinetic hand movements.(Reproduced with permission (sought) from Spence, S. (2006). Hysteria: a new look. In  Psychiatry , 5(2), pp. 56–60, Elsevier Ltd.

1015
may be admitted to the hospital stroke unit, or be sent to the gen-
eral hospital as an emergency with an accompanying letter from the patient’s GP describing the patient as ‘off legs-please see and investigate.’ The following clinical vignette is typical:
A 40-year-old woman was admitted as an emergency to the Stroke

unit of the general hospital after collapsing at home. She had been involved in a dispute with her employers for weeks, and on the morn-ing of the referral had an argument with her mother which made her very upset, and during the course of this she became distressed and developed paraesthesiae down the left side of her body, slurred speech, and collapsed, losing consciousness for 30 s. An ambulance was called and she was admitted to the A and E department, where she was noted to be hyperventilating and agitated, and to have weakness of the left leg, unintelligible speech, and claimed not to be able to see. All neuro-logical investigations were normal, and after 12 days in hospital she made a gradual recovery, but was left with functional weakness in the left leg (requiring a wheelchair), and her speech was intermittently ‘child-like’. History revealed a similar episode 3 years previously, a recent 2-year history of treatment for irritable bowel syndrome, and considerable work and

and her speech was intermittently ‘child-like’. History revealed a similar episode 3 years previously, a recent 2-year history of treatment for irritable bowel syndrome, and considerable work and domestic stress.

She was followed up by the liaison service and community mental 
health team, but despite the efforts of a community physiotherapist, psychologist, and nursing support her limb weakness continued and she remained disabled; 1 year after admission she was in receipt of disability beneﬁ  ts.
(iii) Previous unexplained symptoms
Evidence is accumulating that the more unexplained symptoms the 
patient has, the more likely the primary symptom is to be unexplained by disease.
(28) In a recent study of patients with medically unexplained 
motor symptoms, additional unexplained symptoms including par-aesthesia (65 per cent), pseudo epileptic seizures (23 per cent), and memory impairment (20 per cent) were reported.
(4) It is often useful

(4) It is often useful 
therefore, when CD is being considered as a diagnosis, to obtain a print out of the patient’s past history from the primary care doctor (having obtained the patient’s consent). This may reveal repeated  presentations to different specialists as well as a history of repeated surgical procedures, particularly without clear evidence of pathology. It is also worth noting that patients with a diagnosis of somatization disorder (what used to be referred to as Briquet’s syndrome) have high rates of conversion disorders, which punctuate their illness careers, often after a life event or physical injury/procedure.
(29)
(iv) Psychiatric co-morbidity
Rates of depression (38 to 50 per cent) and anxiety (10 to 16 per cent)have been identiﬁ  ed in a number of studies. In a recent small 
prospective controlled study there was a fourfold increase in depression in comparison with matched control with similar organic disability.
(30)

(30)
(v) Neurological disease and other physical factors
A diagnosis of functional paralysis can be made in a patient who already has some paralysis from another cause, for example, the ‘disproportionate disability’ in a patient with multiple sclerosis. In a recent study of patients with unexplained motor symptoms 42 per cent had a co-morbid neurological disease and half of these had a peripheral origin.
(4) Epilepsy is thought to coexist in a sig-
niﬁ cant percentage of patients with non-epileptic attacks.(31)
It is also important for the physician or surgeon to be aware of 
the diverse ways in which conversion symptoms can present in the general hospital. In the last decade the author has seen many

the diverse ways in which conversion symptoms can present in the general hospital. In the last decade the author has seen many 
patients with conversion disorders after surgical procedures, inves-tigations, and operations such as hysterectomy, minor injuries in the workplace, and after (often trivial) road trafﬁ  c accidents. 
Numerous case reports implicating accidents, minor surgical pro-cedures, and general anaesthetics as initiating factors have been described, for patients with both non-epileptic seizures and func-tional neurological syndromes.
(32–34) These presentations are more 
likely to be seen in a medico legal setting, where the symptoms are shaped by the prospect of ﬁ  nancial gain.
(vi) Secondary gain/litigation
This is a complex issue but impending litigation has been 
described in a number of studies of patients with unexplained motor symptoms and tremor.
(4,35) One group of patients who

(4,35) One group of patients who 
may develop abnormal movements are those with reﬂ  ex sympa-
thetic dystrophy (RSD) which has been renamed Complex Regional Pain Syndrome Type I (CRPS I). It has been reported that patients with CRPS I with abnormal movements typically exhibit pseudo neurological (non-organic) signs, and in some cases malingering has been documented by secret surveillance.
(36)
The authors concluded that abnormal movements in CRPS I are a key clinical feature that differentiates CRPS I from CRPS II. Psychiatrists will often be asked to express opinions on patients with chronic painful extremities (often labelled as ‘CRPS’) in which abnormal movements have developed, especially in a med-ico legal setting. Pearce
(37) has remarked that CRPS is best con-

strued as a reaction to injury, or to excessive, often iatrogenic, immobilization after injury; but should not be seen as an inde-pendent disease. He asserts that the diagnosis of CRPS groups together ill-deﬁ  ned symptoms under a convenient, but medically 
untestable label, and that patients, lawyers, and support groups commonly deny psychogenesis, with the sadly mistaken notion that this implies a bogus or spurious cause.
(vii) Laterality of the symptoms
The idea that left-sided symptoms are more common than right has a long history but a recent systematic review found no evidence to support this view.
(38)
(viii) History from relative/informant
There is a considerable amount of evidence to suggest that the observations and attitudes of carers may be important in the per-petuation of medically unexplained symptoms, especially motor conversion symptoms. For example, Davison et al.
(39) found carers

(39) found carers 
to be ill-informed and dissatisﬁ  ed with the advice they had received 
from doctors about their relatives’ diagnosis and disabilities. The education of carers and relatives is essential and will be dealt with in the section on management.
(b) The examination and diagnostic discrepancies
There is often a discrepancy between the patient’s concept of the symptoms and the physician’s knowledge of the anatomy and phys-iology. The way in which a patient moves or undresses may indicate a global affection that is incompatible with a speciﬁ  c nerve lesion 
or with a hemiplegia.
When considering any sign of functional weakness it is impor-
tant to remember the following caveats:
1 Any sign that depends on inconsistency does not distinguish 
‘hysterical’ from ‘malingered’ weakness.5.2.4 conversion and dissociation disorders

SECTION 5  psychiatry and medicine 1016
2 The presence of a positive sign of functional weakness does not 
exclude the possibility that the patient also has an organic disease 
as well.
3 All physical signs, whether for organic or non-organic signs, have 
a limited reliability and inter-rater reliability.(22)
Another myth wedded to the concept of hysteria (I have already 
referred to the mistaken but common belief that it has ‘disappeared’ and that symptoms are more common on the left) is that the patients exhibit ‘la belle indifference’ or are inappropriately under concerned about their symptoms. In a recent systematic review Stone et al.
(40) found that the median frequency of la belle indiffer-
ence was 21 per cent (range 0–54 per cent) in 356 patients with conversion symptoms and 29 per cent (range 0–60 per cent) in 157 patients with organic disease. Indifference to symptoms is more likely to be noted in patients with factitious disorder (see Chapter 5.2.9).

Give way weakness is often used as a diagnostic test of hysterical 
paralyses, but it is unreliable. Unilateral functional weakness of a leg, if severe, tends to produce a characteristic gait in which the leg is dragged behind the body as a single unit, like a sack of potatoes. The hip is either held in external or internal rotation so that the foot points inwards or outwards. The most impressive quantitative discrimination to date between hysterical and neuro-logical weakness is reported in a study of Hoover’s sign—the invol-untary extension of hysterically paralysed leg when the ‘good leg’ 
is ﬂ exing against resistance. Ziv and colleagues
(41) demonstrated 
a clear difference in the pattern of response between neurological and psychogenic patient groups. It should be borne in mind however that the patient may have both a functional and organic disorder.
(4)
Individual symptoms
(a) Paralyses

(4)
Paralyses may affect one or more limbs, or one side of the face. They may be ﬂ  accid or occur with contractures. In hysterical spasm 
both arm and leg are contracted on the same side of the body, the hand is closed tightly, the knee is ﬂ  exed, and perhaps the leg and 
the foot are drawn up. Paralysis with contractures is one of the most extreme examples of disability caused by hysterical illness.
Hysterical paraplegia has been described,
(42) and both spinal and 
orthopaedic surgeons, as well as rehabilitation specialists and neu-rologists, should be alert to the development of this disorder in their patients.
(43) These patients have the potential to use consider-
able health care resources.(21)
(b) Abnormal movements
Psychogenic movement disorders are thought to account for 1 in 30 of all patients attending a movement disorder clinic
(35) and have 
been the subject of a recent book.(44) During the last two decades a

been the subject of a recent book.(44) During the last two decades a 
number of case series of patients with psychogenic dystonia have been reported.
(45,46)  Clinical features that suggest a psychogenic 
movement disorder are shown in Table 5.2.4.3.
In a recent systematic study of patients with ﬁ  xed dystonia Schrag 
et al .(47) found that 37 per cent fulﬁ  lled criteria for psychogenic 
dystonia and 29 per cent criteria for somatization disorder , which 
is characterized by chronic, multiple, persistent, medically unex-plained symptoms. Despite the fact that many patients fulﬁ  lled 
strict criteria for a somatoform disorder/psychogenic dystonia, in a proportion of patients the diagnosis remained uncertain, and 
whether the disorder was primarily neurological or psychiatric remains an open question. These patients require the services of a multi-disciplinary team.
The most common form of psychogenic movement disorder 
however is psychogenic tremor .

(48) Almost 75 per cent of presenting 
patients are female and preceding events include work-related injuries and other accidents. A positive entrainment test (see Table 5.2.4.3), absence of ﬁ  nger tremor, and slowness of voluntary 
movements are suggestive of psychogenic origin. One-third has co-morbid somatoform disorders and one-ﬁ  fth is involved in liti-
gation or compensation. Prognosis is relatively poor if the condi-tion has persisted for over 1 year, and in the long-term 80–90 per cent of patients continue to have abnormal movements.
(c) Seizures (psychogenic non-epileptic seizures or PNES)
It is estimated that more than 25 per cent of patients receiving a diagnosis of refractory epilepsy in a chronic epilepsy clinic do not have epilepsy.
(49) Although the population incidence of PNES

(49) Although the population incidence of PNES 
may be only 4 per cent that of epilepsy, PNES comprises a large share of the workload of neurologists and emergency and general physicians. Unlike patients with epilepsy however, those with PNES often do not have designated nurses or health care workers assigned to help with the management of this potentially disabling disorder.
PNES can be distinguished from epileptic seizures: PNES gener-
ally occur in the presence of an audience or when one is close at

ally occur in the presence of an audience or when one is close at 
hand. They may be precipitated by stress, but more often seem to occur in response to the social setting. The fall to the ground is not usually abrupt, and movements may follow the fall with clutching, but the characteristic regular tonic–clonic sequence of epilepsy is not found. T ongue biting and incontinence of urine are rare in Table 5.2.4.3  Features that suggest a psychogenic movement 
disorder
Abrupt onset
 ◆  Inconsistent movements (changing characteristics over time)
 ◆  Incongruous movements (movements do not ﬁ  t with recognized 
patterns or with normal physiological patterns)
 ◆   Presence of additional types of abnormal movements that are not 
consistent with the basic abnormal movement pattern or are not 
congruous with a known movement disorder, particularly:
   ÿ Rhythmical shaking
   ÿ Bizarre gait

   ÿ  Deliberate slowness in carrying out the requested voluntary 
movement
   ÿ Bursts of verbal gibberish
   ÿ  Excessive startle (bizarre movements in response to sudden, 
unexpected noise or threatening movement)
 ◆  Entrainment of the psychogenic tremor to the rate of the requested rapid 
successive movement the patient is asked to perform
 ◆ Demonstrating exhaustion and fatigue
 ◆ Spontaneous remissions
 ◆ Movements disappear with distraction
 ◆ Response to placebo, suggestion, or psychotherapy
 ◆ Presence as a paroxysmal disorder
 ◆ Dystonia beginning as a ﬁ  xed posture
(Adapted with permission, from S. Fahn (1995))

1017
hysterical ﬁ  ts, the corneal reﬂ  exes are preserved and the plantars 
are ﬂ exor, unless previously abnormal. Firm handling and pressure 
on the supra orbital nerves to the point of pain may arouse the patient. PNES occur most often among epileptic patients or among others who have seen epileptic ﬁ  ts. A few epileptic patients learn 
how to induce ictal discharges and can produce extra ﬁ  ts. Although 
rarely available during a ﬁ  t, the EEG is generally abnormal in epilepsy
and normal during hysterical ﬁ  ts.
(31)
If PNES is not diagnosed and managed early, signiﬁ  cant iatro-

(31)
genic harm may occur. The outcome is not always favourable in these patients: in one recent study carried out at a mean of 11.9 years after manifestation and 4.1 years after diagnosis of PNES, 71 per cent of patients continued to have seizures and 56 per cent were dependent on social security. Outcome was better in patients with greater educational attainments, younger onset and diagnosis, attacks with less dramatic features, and fewer additional medically unexplained complaints.
(50)
It has recently been reported that patients with PNES have a

(50)
It has recently been reported that patients with PNES have a 
consistently different psychosocial profile from patients with motor conversion symptoms. In a prospective study of consecutive neurological inpatients with either motor conversion or pseudo seizures of recent onset, patients with PNES were younger, more likely to have both an emotionally unstable personality disorder and a lower perception of parental care, to report incest, and to have reported more life events in the 12 months before symptom onset than patients with motor conversion symptoms.
(24) Recently 
a helpful fact sheet has been produced to help patients with PNES, which explains the nature of the disorder and approaches to management.
(51) Although cognitive–behavioural therapy has been 
shown to be helpful in an open trial of patients with PNES, these ﬁ ndings need replication in a controlled setting.
(52)
Sensory symptoms
(a) Sensory disturbance

(52)
The clinical detection and localization of sensory dysfunction is 
probably one of the least reliable areas of the neurological exami-nation. Sensory loss may involve half the entire body from top to toe or from right to left. It may affect the whole of a limb, and char-acteristically has a glove or stocking distribution on the arms or legs, or both. The sensory loss generally fails to ﬁ  t in with known 
anatomical boundaries but conforms more with the patient’s concept of physiology and anatomy. Thus hysterical sensory loss is likely to stop sharply at the midline, while non-hysterical sensory change will only approach the midline since at this point segmental nerves overlap by one or two centimetres on each side.
Unfortunately these classical signs are often unreliable.

Unfortunately these classical signs are often unreliable. 
‘Psychogenic’ features on sensory examination and diminished 
vibration sense over the affected part of the forehead have been 
found in over half of patients with neurological disorders.
(53, 54)
Rolak also found that ‘midline splitting’ of sensory function was 
not helpful in determining whether there was an underlying neurological disorder.
(54) These clinical ﬁ  ndings should clearly be 
interpreted with circumspection.
T oth has recently described 34 patients with the ‘hemisensory’ 
syndrome, in which patients present with hemisensory disturbance and intermittent blurring of vision in the ipsilateral eye (astheno-pia) and sometimes ipsilateral hearing problems as well.
(55)
Hemisensory symptoms are increasingly recognized in patients with chronic pain and in patients with reﬂ  ex sympathetic dystrophy.(b) Visual disturbances
Ophthalmologists have estimated that psychogenic visual disorders

Ophthalmologists have estimated that psychogenic visual disorders 
account for up to 5 per cent of their practice.(56) Simple observa-
tion of visually guided behaviour will sometimes reveal telling inconsistencies, particularly in the case of severe apparent visual loss. A number of reliable optometric techniques are available to support bedside tests and the diagnosis of psychogenic visual loss, ﬁ eld disturbance, or gaze abnormality (for more details see Stone 
et al.
(23)). Disabling hysterical blindness presents more difﬁ  culties. 
Evoked potential studies will help to demonstrate intact visual pathways.
The disability associated with chronic 
conversion disorders
This topic is under-researched, but it is worth noting that, as the

This topic is under-researched, but it is worth noting that, as the 
prognosis of CD is often poor, (not infrequently because patients are not diagnosed promptly, and even after diagnosis there are no resources to treat the patient). In the experience of the author this clinical conundrum is not improving: with the increase in pro-vision of psychiatric services to the community and those with ‘serious mental illness’ , patients with CD, even if they are profoundly disabled, often do not receive the appropriate treatment. Much of the disability is iatrogenic, and these patients will, not infrequently, be referred to the psychiatric service after having become conﬁ  ned 
to a wheelchair and/or in receipt of long-term disability bene-ﬁ ts.
(21,39)  By this time the patients are usually entrenched in the 
sick role and it is very difﬁ  cult to change the status quo.
Prognosis

Prognosis
The aetiological implications accruing from recent follow-up stud-
ies(4, 57) suggest that a short history and young age are held to be 
predictors of good outcome, while the presence of a personality disorder, chronicity of symptoms, receipt of disability beneﬁ  ts, and 
involvement with litigation predict poor recovery. As regards social circumstances, a change in marital status, good family functioning, and the elimination of a stressor has been shown to have a positive effect on outcome.
(58) There is little chance of improvement once 
the symptoms have become chronic and enduring.
Patients with chronic motor symptoms, e.g. unilateral functional

Patients with chronic motor symptoms, e.g. unilateral functional 
weakness, as well as those with sensory symptoms, appear to do particularly poorly. In particular, patients with unexplained motor symptoms who are referred to tertiary care centres continue to do very poorly following discharge. Despite the stability of the diagno-sis, a pattern of multiple hospital referrals continues for many of these patients once they have been discharged from the tertiary care centre. Interviews of patients conducted on an average of 6 years after their original admission to a tertiary care centre revealed that many continued to be referred to neurologists and other specialists, but that subsequent psychiatric referral was rare.
(59)

(59)
Many changed their primary care doctor after discharge from hos-pital and a disproportionate number of re-referrals were made by primary care doctors who had known their patients for less than 6 months. Psychological attribution of symptoms was rare, and many patients felt dissatisﬁ  ed with the treatment they had received. 
Many were exposed to unnecessary iatrogenic harm. These consis-tent ﬁ  ndings of very poor outcome following discharge from 
neurological outpatient and inpatient services in patients with both 5.2.4 conversion and dissociation disorders

SECTION 5  psychiatry and medicine 1018
unexplained motor disorders as well as PNES suggest that without 
appropriate treatment the prognosis is poor.
It is remarkable that a disorder as common as schizophrenia 
and multiple sclerosis should have attracted so little research inter-est or treatment resources. One reason for this is that there have been no randomized controlled treatment studies of CD, and so at the time of writing there is no good evidence about the best intervention for conversion disorder. There has been considerable interest in this topic however, which has been the subject of a recent Cochrane review.
(60) All of the studies in this review were of 
poor methodological quality. On the credit side there is evidence that interest in CD is increasing and attracting more research funding.
Resources

Before any discussion of treatment it is important to consider the resources available to the neurologist to manage these patients. It is anomalous that, unlike disorders such as MS and schizophrenia, which have a similar prevalence, there are no designated resources for these patients. Some neurologists may have no access whatever to mental health resources, whereas others may have close collab-orative links with either clinical psychology or psychiatry services. There is no doubt that the successful management of these patients requires the co-operation of a number of clinical specialties, includ-ing psychologists, nurses, physiotherapists, and occupational therapists (OTs). Some patients may be so disturbed or disabled (or both) that they may require inpatient admission to a specialized unit with access to both, mental health care and medical nurses, as well as physiotherapists and OTs. In the opinion of this writer every neurology service should have access to a specialist liaison

unit with access to both, mental health care and medical nurses, as well as physiotherapists and OTs. In the opinion of this writer every neurology service should have access to a specialist liaison psychia-try service.

(61)
Management strategies for the neurologist
First, the diagnosis has to be established by a neurologist after rel-evant organic disease has been excluded. Second, the neurologist has to not only explain to the patient that there is no serious under-lying organic disease but also provide an explanation for the symp-toms that is comprehensible to the patient.
It is worth noting at this stage that patients prefer the term ‘func-
tional’ rather than ‘hysterical’ , when their unexplained weakness, ﬁ ts, etc. are being referred to.
(62) It is also important to avoid verbal 
landmines—for example using the phrase ‘not sinister’ instead of ‘not serious’; or ‘not structural’ instead of ‘not physical’ . In patients who are generally hostile to psychological explanations it is best to use the word ‘functional’ instead of ‘psychological’ .
An example of an explanation to a patient with functional weak-
ness and sensory disturbance may be something like: you have what

ness and sensory disturbance may be something like: you have what 
we call functional weakness. This is a common medical problem. Your nervous system is not damaged—we can see that from the examina-tion and scans, etc. This is why why when you try and send the mes-sages to your limbs they do not move properly. Similarly this is why the sensations from your body are not being felt properly. The most important thing about this condition is that because your nervous system is not damaged, the problem is potentially reversible. All the parts of the nervous system are there but are just not working properly, so that when you try to move your leg it doesn’t do it as well as it should. Sometimes stress can cause these symptoms, which are often

accompanied by worry and low mood but these are not the cause of the problem. Stress is a common problem and can lead to headache and abdominal pain as well as what we call functional weakness .
This explanation can be supplemented by giving the patient a 
fact sheet  containing information about functional weakness, 
which contains information about how to become involved with rehabilitation
(51) (Fig. 5.2.4.3).
Further management
Ideally the neurologist and psychiatrist should interview the patient together at the bedside, but this is not always possible. At the very least however close collaboration between the two is essential before the patient is reviewed by the psychiatrist and a formulation proposed (and any potential for iatrogenic illness or diagnostic confusion eliminated).
Traditional behavioural approaches to treatment are based on the

Traditional behavioural approaches to treatment are based on the 
premise that the symptoms reported by the patient are interpreted as physical but are amenable to recovery. Treatment aims to bring about a gradual increase in function through a combination of physical and occupational therapies. The patient receives rewards and praise for improvement of function, and withdrawal of reinforcement for con-tinuing signs of disability. Avoiding direct confrontation of psycho-logical problems and providing ‘face-saving’ techniques are also regarded as key components.
(63) More recently the approach to 
patients has moved from a predominantly medical one, to one in which psychological and sociocultural aspects are equally important, and the need for organized specialist rehabilitation services involving a multi-disciplinary team is recognized as essential.
What is the evidence?
With one or two recent exceptions,(64) there are no large, random-

ized controlled studies of treatment in patients with CDs. Neither is there any good evidence to support the use of one speciﬁ  c inter-
vention, e.g. biofeedback, hypnosis, psychotherapy. Although repeated case series have documented the effectiveness of multi-disciplinary inpatient behavioural treatment, there is little con-trolled research.
In the absence of good experimental evidence a possible frame-
work for future research has been developed which is based on published evidence and described in the WHO ICIDH.
(65) This is 
particularly useful for patients in whom there is a disability that is out of proportion to known disease and signs. The model provides opportunities for intervention, and is well suited to the kind of multi-disciplinary approach that is likely to be successful in these patients.
The model emphasizes that whatever the primary cause of an

The model emphasizes that whatever the primary cause of an 
illness, many factors (both individual and systemic) will have an inﬂ uence on its manifestations. For example: a vignette here .
A 20-year-old woman was referred to the liaison service with 
functional paraplegia of 12 months duration. Onset was temporally related to a back strain caused by lifting a chair. She was conﬁ  ned to 
a wheelchair and lived with her parents and 14-year-old brother in an adapted house (specially adapted chair and stair rails) and was in 
receipt of beneﬁ  ts. A home visit was carried out and the patient denied 
any current problems or recent life events, although she described a long history of medically unexplained symptoms, multiple food allergies, and previous treatment in an adolescent unit for chronic

1019
fatigue syndrome. She was seeing a chiropractor for her symptoms, 
and had been told that she had nerve damage (not conﬁ  rmed). Her brother was off school with chronic fatigue and her mother had a long history of emotional problems. At interview, the family were polite but could not identify any link between recent events and her disabling symptoms. Discussion with the GP did not reveal any other relevant information and a follow-up was arranged 1 month later. Before this appointment the patient telephoned the psychiatrist to say that she 
had not disclosed certain facts at the initial meeting, and revealed that 
she had confronted her physically abusive step father and asked him to 
leave the house to live with his mistress (which he duly did). At follow-
up there was a great deal of expressed relief, and the patient agreed

up there was a great deal of expressed relief, and the patient agreed 
with our formulation that, to some extent, she had developed weak-ness in the legs and become wheelchair bound in order to avoid being hit by her step father. She agreed to a brief admission to a rehabilita-tion unit, was encouraged to mobilize gradually and had regular ses-sions with a clinical psychologist. She responded well to treatment, commenced a college course, and learned to drive a car. At 3 year fol-low-up she was symptom free and in gainful employment. [the ﬁ  rst vignette in this chapter] .
Because patients with conversion disorders share features in com-
mon with patients with other medically unexplained syndromes, treatments that have been used in these latter disorders may have potential. Most of the evidence-based treatments in this ﬁ  eld 
involve cognitive–behavioural therapy (CBT,

(66) or interpersonal 
therapy (IPT)). These usually have to be undertaken by trained clinical psychologists or other clinicians. However, increasing num-bers of specialist nurses are being trained to deliver these treat-ments, so they should become more widely available.
CBT is concerned mainly with helping the patients overcome 
identiﬁ  ed problems and ascertain speciﬁ  ed goals. It discourages 
‘maintaining factors’ such as repeated body self-checking and 
excessive bedrest, and challenges patients’ negative or false beliefs 
about symptoms. Chalder has described speciﬁ  c CBT based treat-
ment for patients with conversion disorders.
(67)
Hypnosis and intravenous sedation
In an inpatient trial of hypnosis both patients with CD and 
controls improved equally and no extra effect from hypnosis was found.
(68) Others have found the use of intravenous sedatives,

(68) Others have found the use of intravenous sedatives, 
particularly propofol, helpful in persuading some patients with whom a good relationship has been established, that they can even-
tually make a recovery.
(51)
There is evidence from randomized controlled trials (RCTs) and systematic reviews that antidepressants (both tricyclics and selective Fig. 5.2.4.3 Fact sheet for patient with functional weakness (Reproduced from Stone, J. Carson, A. and Sharpe, M. (2005), Functional symptom s in neurology: 
management.  Neurology in Practice , 71(Suppl. 1), i13–i21. Copyright 2005, BMJ Publishing Group Ltd.)
5.2.4 conversion and dissociation disorders

SECTION 5  psychiatry and medicine 1020
serotonin reuptake inhibitors (SSRIs)) can be useful in the treat-
ment of patients with medically unexplained symptoms (such as 
poor sleep and pain), whether or not depression is present.(69)
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patients with symptoms unexplained by disease? The number needed to offend. British Medical Journal ,325, 1449–50.

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somatisation and symptom syndromes: a critical review of controlled clinical trials. Psychotherapy and Psychosomatics ,69, 205–15.

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cognitive-behavioral therapy for symptom syndromes. CNS Spectrum ,
11, 212–22.
5.2.5 Hypochondriasis 
(health anxiety)
Hypochondriasis is a preoccupation with the fear that one has,

Hypochondriasis is a preoccupation with the fear that one has, 
or may develop, serious disease despite evidence to the contrary. So deﬁ ned, the disorder affects between 2 and 7 per cent of patients 
attending general medical clinics and is a cause of physical dysfunc-tion and disability.
(1) It is also a reason for increased health 
care utilization and dissatisfaction with care received. T o their physicians, patients with this disorder are an enigma and a source of frustration.
Unfortunately, relatively little is known about hypochondriasis. 
Primary care physicians have had little interest and psychiatrists see few patients with the condition. It is a pejorative label that, even if entertained, is rarely communicated. And, even if communicated, the diagnosis would not, until very recently, have led to effective treatment.
History

History
Hypochondria was used by Hippocrates to refer to a region below the cartilage of the ribs. In the second century, Galen linked it to organs in this area as well as humours and animal spirits. The symptom picture was ill-deﬁ  ned and only gradually took on the 
characteristics recognized today. From earliest times the disorder was associated with melancholia, a temperamental disturbance caused by an excess of black bile. Burton (1621) described hypo-chondriacal melancholy in terms of vague physical symptoms, dis-turbances of mood, and fears. In the seventeenth century, Sydenham viewed hypochondria in men as the counterpart of hysteria in women, but the ﬁ  rst modern description was published in 1799 
by Sims.
By the eighteenth century, hypochondria became part of a fashion-
able disturbance that Cheyne attributed to the English way of life 
and environment. However, as notions of aetiology began to shift

and environment. However, as notions of aetiology began to shift 
under the influence of Cartesian dualism, hypochondria was increasingly seen as a weakness and moral failing. Falret (1822) was 5.2.5 hypochondriasis (health anxiety)

SECTION 5  psychiatry and medicine 1022
perhaps the ﬁ  rst to identify it as a mental disorder, one of the 
neuroses. Freud viewed hypochondria as an ‘actual neurosis’ , having a physiological basis and not amenable to psychoanalysis. However, present-day descriptions began with Gillespie,
(2) who in 
1928 deﬁ  ned hypochondriasis as ‘a mental preoccupation with a 
real or supposititious physical or mental disorder’ .
Conceptualizations
Authors disagree about how hypochondriasis should be conceptu-alized. Some look upon it as a personality trait; its early onset and long-term stability in many patients ﬁ  t this conception. Others

Authors disagree about how hypochondriasis should be conceptu-alized. Some look upon it as a personality trait; its early onset and long-term stability in many patients ﬁ  t this conception. Others 
view it as a dimension of psychopathology. They see illness worry as a continuum with hypochondriasis falling on the severe end. For those who take a categorical approach, the issue of whether hypochondriasis is primary or secondary remains unsettled. High rates of comorbidity create doubt about its independent status. Based on existing evidence, some question whether hypo-chondriasis can be regarded as a discrete psychiatric disorder.
(3)
Clinical picture
Essential features
The essential characteristics of hypochondriasis are shown in Table 5.2.5.1. These include fear of serious disease, the consequenc-es of which may include pain, suffering, disability, and death. Such fears take the form of alarming thoughts and images of speciﬁ  c

diseases. They also include conviction or belief that the feared dis-ease is already present. This belief is overvalued meaning that it is strongly held despite lack of evidence; it is not delusional.
Bodily preoccupation is perhaps the most important feature.
(4)
This takes the form of intense interest in, and attention to, what is happening in the body. The focus is upon somatic symptoms which tend to be multiple and diffuse. Attention is also directed to bodily sensations, bodily functions, and minor abnormalities as well as related concerns such as diet, exercise, and environmental exposures. 
The activities and conversation of patients are dominated by medi-
cal concerns. As a consequence of their self-absorption, interest in other people and pursuits is withdrawn.
Reassurance-seeking is the main behavioural feature. Patients

Reassurance-seeking is the main behavioural feature. Patients 
repeatedly check their bodies for signs of serious disease. They check their pulse, look for lumps, examine themselves in the mirror, etc. In addition, they search medical sources for the meaning of their symptoms. Such patients also ask friends, family, and medical professionals for reassurance. Their search may lead to excessive utilization of health services.Associated features
Associated characteristics include fears of aging and death, which appear to be an integral part of hypochondriasis. Overvaluation of health and appearance is another related feature. Hypochondriacal patients may become preoccupied with eating natural foods, achieving physical ﬁ  tness, and living a healthy lifestyle, activities 
that reﬂ  ect their idealized conception of good health.

Patients with hypochondriasis feel unworthy and unlovable.
(4)
As a consequence of their low self-esteem they have negative expec-tations of others including medical professionals. In addition, they have a sense of vulnerability to illness.
(5) These characteristics 
have to do with fundamental aspects of the self that the hypochon-driacal patient views as deﬁ  cient.
Subtypes
Hypochondriacal patients are heterogeneous and subtypes may 
exist. Separate dimensions of disease phobia and disease conviction have consistently been identiﬁ  ed; in some patients fears are promi-
nent and in others conviction dominates the picture. Others may resemble patients with obsessive-compulsive disorder or personal-ity disorders of one kind or another.
Criteria
Hypochondriasis initially appeared in DSM-II as one of the neuro-

Criteria
ses. In DSM-III, it was moved to the somatoform disorders, and diagnostic criteria were provided. In a revision of the classiﬁ  cation 
(DSM-III-R), a duration of 6 months was added, and patients with delusional beliefs were excluded. The DSM-IV criteria are shown in Table 5.2.5.2. They exclude patients whose symptoms are better explained by other anxiety, depressive, or somatoform disorders.
(1)
Also, in DSM-IV , speciﬁ  c phobia of illness is separated from hypo-
chondriasis. The illness phobic is said to fear contracting an illness whereas the hypochondriac fears disease already present.
The ICD-10 criteria for hypochondriacal disorder differ from 
those in DSM-IV . They require a persistent belief about having one or more speciﬁ  cally named serious physical diseases.
(6) In addition,

(6) In addition, 
they include body dysmorphic disorder. With respect to illness behaviour, the ICD-10 criteria state that hypochondriacal concerns cause persons to seek medical investigation or treatment. They also state that patients may accept reassurance in the short-term, but that in the long run they are not likely to respond.Table 5.2.5.1  Essential and associated features of hypochondriasis
 Fear of disease
 Disease conviction Bodily preoccupation
 Somatic symptoms
 Reassurance-seeking
Associated features
 Fear of aging and death
 Overvaluation of health Low self-esteem
 Sense of vulnerability to illness
Table 5.2.5.2  Abbreviated DSM-IV diagnostic criteria for 
(a)  Preoccupation with fears of having, or the idea that one has, a serious 
disease based on misinterpretation of bodily symptoms

(b)  The preoccupation persists despite appropriate medical evaluation and 
reassurance
(c) Belief not of delusional intensity(d) Preoccupation causes signiﬁ  cant distress or impairment(e) Duration of at least 6 months(f)  Not better accounted for by other anxiety, depressive, or somatoform 
disorders

1023
The somatoform disorders category to which hypochondriasis 
belongs is controversial, and many question its inclusion in the classiﬁ  cation.
(7) They see these disorders as ill-deﬁ  ned, of question-
able validity and based more on illness behaviour than on dis-tinctive features. They also view them as creations of Western biomedicine that serve to devalue patients who challenge the theo-retical model upon which it is based.
(8) According to that model, 
illness is a response to disease, and the person who is ill without disease, e.g. hypochondriasis, is marginalized.
Were the somatoform disorders to be eliminated, some have pro-
posed moving hypochondriasis to the anxiety disorders (health anxiety) or to a proposed grouping, the obsessive-compulsive spec-trum disorders.
Validity
Evidence for the validity and utility of the diagnosis of hypochon-driasis remains limited. In studies aimed at demonstrating validity, Barsky et al .

Validity
(9) showed that distinguishing characteristics of the 
disorder aggregated in some medical outpatients but were less common in others. The same patients had other features of hypochondriasis indicating external validity. Using a structured interview for hypochondriasis, these investigators and others
(10,11)
observed a positive correlation between interview and physician ratings (concurrent validity). Hypochondriacal patients also had more ancillary features of hypochondriasis than did control patients (external validity). Also, other clinical characteristics distinguished interview positive from interview negative patients, indicating discriminate validity. Follow-up studies have shown a degree of diagnostic stability suggesting predictive validity.
(12,13)
Measures

(12,13)
Measures
A variety of measures have been developed to screen for hypochon-driasis and assess the severity of hypochondriacal concerns.
(14)
These are shown in Table 5.2.5.3. The Whiteley Index, a self-report instrument based on the observed characteristics of hypochondria-cal psychiatric patients, is one of the most widely used.
(15) It con-
sists of 14 yes versus no items, but recent work suggests that a 7-item version is satisfactory for screening. The Illness Attitude Scales is a 27-item measure of psychopathology associated with hypochondriasis.
(16) A principal components’ analysis yielded 
two factors, one measuring health anxiety and the other illness behaviour. The health anxiety subscale has been used to distinguish 
hypochondriacal from non-hypochondriacal patients.
Recently, self-assessment measures have been developed to assess

Recently, self-assessment measures have been developed to assess 
the various dimensions of health anxiety and hypochondriasis. The Health Anxiety Inventory contains 47 items covering a range of hypochondriacal features.
(17) An advantage of this scale is that it 
distinguishes patients with high health anxiety from those with physical illness.
The Structured Clinical Interview for DSM-IV (SCID) and the 
Composite International Diagnostic Interview (CIDI) are compre-hensive diagnostic interviews that contain somatoform disorder modules. The CIDI has been used in epidemiologic surveys. Its stem question for hypochondriasis is, ‘In the past 12 months, have you had a period of 6 months or more when most of the time you worried about having a serious physical illness or deformity?’
Based on the SCID, Barsky et al.
(10) developed a structured inter-

view that focuses exclusively on hypochondriasis. It begins with a series of probe questions that, if answered afﬁ  rmatively, trigger the 
remaining interview. It is suitable for conﬁ  rming the diagnosis in a 
screened population.
Diagnostic assessment remains less than satisfactory because 
the threshold for caseness has not been established, medical and psychiatric comorbidity make diagnostic decision-making difﬁ  cult, 
and independent medical evaluation is rarely part of the process.
Physical disorders

A few hypochondriacal patients suffer from undetected physical disease. Consequently, it is important to exclude medical conditions that, in their early stages, may cause vague symptoms with few signs or laboratory abnormalities. These include neurological conditions, such as multiple sclerosis or myasthenia gravis; endocrine condi-tions, such as thyroid or parathyroid disorders; multisystem disease such as systemic lupus erythematosus or occult malignancies. Because of such possibilities, a physical cause warrants continuing consideration even after the initial work-up has been completed.
Patients with panic disorder  may be difﬁ  cult to distinguish from

Patients with panic disorder  may be difﬁ  cult to distinguish from 
those with hypochondriasis because they commonly have hypochon-driacal features. A diagnosis of hypochondriasis should not be made if illness concerns are better accounted for by panic disorder. Patients with hypochondriasis tend to fear the long-term consequences of ill-ness (such as cancer) whereas those with panic fear the immediate consequences of illness events (such as a heart attack); the former fear death, the latter dying. Also, those with hypochondriasis misinterpret a range of bodily sensations, whereas those with panic misinterpret the symptoms of autonomic arousal.
Hypochondriasis must be distinguished from speciﬁ  c phobia ,
illness subtype .
(1) Patients with hypochondriasis are preoccupied

(1) Patients with hypochondriasis are preoccupied 
with a disease they believe is already present, whereas illness pho-bics fear developing a disease they do not yet have. Illness phobic symptoms are triggered by external as well as internal cues. For instance, exposure to a person with the feared disease may elicit a fear response.
Hypochondriasis must be distinguished from obsessive-
compulsive disorder . Patients with the latter often have intrusive 
thoughts about disease or contamination and rituals that involve Table 5.2.5.3  Measures for the assessment of hypochondriasis
Self-rated questionnaires
 Whiteley index
 Illness worry scale
 Illness attitude scales Health anxiety questionnaire
 Health anxiety inventory
 Multidimensional inventory of hypochondriacal traits Psychiatric diagnostic screening questionnaire
Structured interviews

Health anxiety inventory
 Structured diagnostic interview for hypochondriasis Structured clinical interview for DSM-IV
 Composite international diagnostic interview
 Schedules for clinical assessment in neuropsychiatry5.2.5 hypochondriasis (health anxiety)

SECTION 5  psychiatry and medicine 1024
checking or reassurance-seeking. They differ from patients with 
hypochondriasis in having other obsessions and compulsions. Obsessive-compulsive patients tend to regard their ideas as sense-less and resist them, whereas those with hypochondriasis regard them with conviction.
Hypochondriasis must also be distinguished from generalized 
anxiety disorder  which is characterized by excessive worry about a 
number of areas. These may include health but other areas are generally involved as well. If worry is conﬁ  ned to illness, then a 
diagnosis of GAD should not be made. Patients with GAD tend to have health worries that are general, whereas those with hypo-chondriasis involve speciﬁ  c diseases such as cancer.
Hypochondriasis that develops during an episode of major 
depression  and remits with treatment of the mood disturbance may

depression  and remits with treatment of the mood disturbance may 
be better accounted for by the depressive disorder. In that case, the patient is likely to focus concern upon the vegetative symptoms of depression and interpret these as irreversible loss of health. On the other hand, a diagnosis of hypochondriasis may be appropriate when hypochondriacal concerns are not conﬁ  ned to an episode of depres-
sion and are not focused on symptoms of the mood disorder.
Hypochondriasis and somatization disorder  are both character-
ized by somatic symptoms. However, patients with hypochondria-sis worry about the meaning of symptoms rather than the symp-toms themselves. They are concerned about the consequences of serious illnesses rather than securing the gains of illness (e.g. sick role) as are patients with somatization disorder. Patients with hypochondriasis have an equal sex distribution whereas those with

somatization disorder are predominantly women.
Hypochondriacal beliefs of a delusional nature may occur in 
patients with psychoses, but these patients usually have other psychotic features. However, delusions of disease may be the main or only manifestation of delusional disorder, somatic type . Such 
delusions may be bizarre or unrealistic, whereas the beliefs of patients with hypochondriasis are overvalued.
The prevalence of hypochondriasis in the general population  has 
not been established. Major surveys of psychiatric disorders have either excluded the somatoform disorders or identiﬁ  ed few cases. 
For instance, Looper and Kirmayer
(18) found that 6 per cent 
responded afﬁ  rmatively to screening for illness worry, but only 
0.2 per cent met full criteria for hypochondriasis according to a structured interview. Two studies that focused exclusively on somatoform disorders obtained higher estimates (4.5 and 7.7 per cent).

(19, 20)  Two other surveys focusing on illness worry found that 
half the respondents with such worry had the illness they worried about.
(18, 21)  Among such people it may be difﬁ  cult to distinguish 
excessive from normal worry.
The prevalence of hypochondriasis among primary care outpa-
tients  had been examined in a number of studies. In a cross-
national survey, Gureje et al .(22) noted that, if the criterion of 
failure to respond to reassurance were set aside, 2.2 per cent of patients qualiﬁ  ed for this diagnosis and were as impaired as those 
meeting full criteria. In studies based on structured interviews, prevalence estimates have ranged from 2.2 per cent to 9.4 per cent.
Hypochondriasis may be prevalent in medical specialty popula-

tions  where patients with functional disturbances are common. For instance, one survey found the disorder in 13 per cent of otolar-
yngology clinic patients. Also, hypochondriacal concerns are higher in patients with functional than with organic illnesses. For example, in one study higher hypochondriasis scores were obtained from patients with irritable bowel syndrome than from patients with organic gastrointestinal disease. Hypochondriacal concerns and health anxiety are especially high in patients with chronic pain.
High health anxiety is one of the factors shared by functional 
somatic syndromes in the general population.
(23) However, it is not 
clear whether this represents a vulnerability factor or a consequence of unexplained symptoms.

Risk factors for unexplained somatic symptoms include female gender, older age, non-white race, less education, and lower income. With respect to hypochondriasis, few of these demographic factors appear important although ﬁ  ndings have been inconsistent. The 
risk for men appears to be equal that for women. Some studies have shown persons with illness worry and hypochondriasis to be older and to have more physical illness. Two studies found them to have less education.
Hypochondriacal patients in primary care have high levels of psy-chological as well as somatic symptoms. Strong positive correla-tions have been observed between hypochondriacal concerns and depressive ( r = 0.58), anxiety ( r = 0.55), and somatic symp-
toms ( r = 0.52). In one study, the proportions of hypochondriacal

toms ( r = 0.52). In one study, the proportions of hypochondriacal 
and control patients, having one or more comorbid disorder, were 62 and 30 per cent respectively. Anxiety and depressive disorders accounted for most of the excess.
Family and twin studies
Taylor et al .(24) used a twin study to examine the genetic and 
environmental contribution to excessive health anxiety. After con-trolling for medical morbidity, which may be a source of health anxi-
ety, they found that genetic factors accounted for 37 per cent of the variance in fear of disease and 10 per cent in disease conviction. For both dimensions the remainder of the variance (63 and 90 per cent respectively) was accounted for by non-shared environmental factors. These and other results suggest that some dimensions of health anxiety are moderately heritable. They also suggest that such anxiety is largely a learned phenomenon.
A family study compared the ﬁ  rst-degree relatives of probands

A family study compared the ﬁ  rst-degree relatives of probands 
with and without hypochondriasis obtained from a general medi-cine clinic.
(25) No difference in the frequency of hypochondriasis 
was found between these groups of family members. However, certain traits and attitudes, such as hostility, low agreeableness, and dissatisfaction with care, were signiﬁ  cantly higher among the 
relatives of hypochondriasis probands. Such traits and attitudes may confer vulnerability to hypochondriasis and/or other somato-form disorders.
Morbidity and service utilization
Hypochondriasis is associated with impairment in physical func-tioning and work performance. Patients with this disorder view their health as worse, and experience more physical disability as well as impairment in occupational roles than patients without hypochon-driasis.
(10, 11) They use more medical services yet are less satisﬁ  ed

1025
with them than non-hypochondriacal patients. This increased utili-
zation includes physician visits, laboratory tests, outpatient costs, and hospitalizations. Hypochondriacal patients tend to feel that their medical problems have not been thoroughly evaluated and as a con-sequence consult many physicians (i.e. doctor-shopping).
Hypochondriasis and health anxiety tend to be associated with 
increased symptom reporting and functional impairment, although the ﬁ  ndings from various clinical populations have been inconsis-
tent. For instance, hypochondriacal concerns are associated with higher disability and lower quality of life among patients with irri-table bowel syndrome, chronic fatigue, and ﬁ  bromyalgia.
(26) One

(26) One 
study found hypochondriasis the strongest predictor of pain due to osteoarthritis, and another showed high health anxiety predictive of abdominal pain 1 year later. Hypochondriasis was also a predic-tor of disability in patients with coronary artery disease. Consistent with these observations, hypochondriasis is associated with increased reporting of, and distress from, medication side effects.
Personality
Hypochondriacal concerns are strongly related to the major per-sonality dimension of neuroticism or negative emotionality.
(27)
Positive correlations between neuroticism and hypochondriacal concerns ranging from 0.4 to 0.5 have consistently been observed in non-clinical samples. Neuroticism refers to a tendency to experi-ence and report negative emotions and overreact to stress. Persons high on this dimension are prone to ﬁ  nd bodily sensations noxious

and interpret them as signs of serious illness. Neuroticism may represent a vulnerability factor for hypochondriasis.
Certain personality traits may have more to do with difﬁ  cult 
patient–doctor relationships than with hypochondriasis itself. Patients with hypochondriasis have been described as angry and mistrustful. Such characteristics might reﬂ  ect negative emotions 
belonging to the domain of neuroticism or the negative pole of agreeableness, another of the major personality dimensions. They 
might also reﬂ  ect obsessive-compulsive or masochistic personality 
traits observed in some patients.
Developmental factors
Childhood inﬂ  uences appear to be important in the development 
of hypochondriasis. Reports of traumatic events during child-
hood , including physical and sexual abuse, have been elicited more 
frequently from hypochondriacal than non-hypochondriacal patients. Although ﬁ  ndings are preliminary, they are consistent

frequently from hypochondriacal than non-hypochondriacal patients. Although ﬁ  ndings are preliminary, they are consistent 
with a literature linking childhood neglect and abuse to unexplained somatic symptoms in adults.
Childhood experience of illness  may contribute to the develop-
ment of hypochondriasis. For instance, Noyes et al .
(28) obtained 
reports of serious illness or injury before age 17 from a third of adults with hypochondriasis. Similar ﬁ  ndings from patients with 
hypochondriasis and somatization have been reported by others. Early illness may create a sense of physical vulnerability in suscep-tible individuals. Childhood exposure to serious illness or death of a family member or friend may do likewise.
Parental attitudes  may also contribute to hypochondriasis.

Parental attitudes  may also contribute to hypochondriasis. 
Excessive concern for a child’s health or overprotection on the part of a parent may lead to anxiety about health as may special caretaking and rewards for illness. A child may also model exaggerated illness behaviour displayed by a parent. The importance of devel-
opmental factors—early adversity, experience of illness, over solici-tous parents—suggest that hypochondriasis is in large measure learned behaviour.
Stressful life events appear to be related to increased reporting of physical symptoms and hypochondriasis, although there have been few studies. Events involving illness and death may have a speciﬁ  c

role as the symptoms of hypochondriacal patients sometimes resemble those of family members who have been ill or died. In addition, illness events may give rise to hypochondriacal symp-toms; ‘cardiac neurosis’ following myocardial infarction is an example. Transient hypochondriasis has been observed following medical illness in predisposed individuals.
Cognitive and perceptual factors
According to the cognitive-perceptual model, hypochondriasis is based on misinterpretation of bodily symptoms as signs of serious disease and on the experience of somatic sensations as intense, noxious, and disturbing.
(29) In this model, the faulty attribution of 
innocuous sensations is the central defect. A number of studies have shown that, when symptoms are attributed to pathological processes, they become intensiﬁ  ed. Such attribution may focus

innocuous sensations is the central defect. A number of studies have shown that, when symptoms are attributed to pathological processes, they become intensiﬁ  ed. Such attribution may focus 
attention on symptoms thereby amplifying them. Misinterpretation of this kind may arise from cognitive schemata that were estab-lished through earlier experience with illness.
The tendency to experience bodily sensations as intense and dis-
turbing has been termed somatosensory ampliﬁ  cation. One study 
that used the Somatosensory Ampliﬁ  cation Scale found a positive 
correlation of 0.56 between ampliﬁ  cation and hypochondriasis. This 
ﬁ nding suggests that individuals with hypochondriasis have a consti-
tutionally lowered threshold for physical symptoms or that they have a heightened attentional focus and increased physiological arousal.
Evidence of physiological abnormalities was obtained by
Gramling et al .
(30) In a preliminary investigation, they observed

(30) In a preliminary investigation, they observed 
physiological reactivity that distinguished women with hypochon-driasis from those without. Hypochondriacal subjects had a higher mean heart rate and lower mean hand temperature during a cold pressor test compared to controls. These subjects terminated the test more frequently and rated it as more unpleasant than did controls.
Interpersonal factors
According to the interpersonal model, hypochondriasis is a form of care-eliciting behaviour that finds expression in physical complaints. Through unexplained somatic symptoms and expres-sions of illness worry, patients with this disorder seek emotional and interpersonal support from family members and physicians. Need for support of this kind arises from insecure attachment that originated in early relationships with caregivers. In a test of this model, Noyes et al.
(31) found that hypochondriacal concerns among

(31) found that hypochondriacal concerns among 
primary care patients were associated with various insecure attach-ment styles. These concerns were also associated with interpersonal problems and lack of reassurance from medical care.
Social and cultural factors
Social and cultural factors are important determinants of hypo-chondriasis. Throughout the world physical symptoms are com-mon vehicles for the communication of distress. Somatic distress 5.2.5 hypochondriasis (health anxiety)

SECTION 5  psychiatry and medicine 1026
gains the attention of family and community  because it signals 
impairment in functioning that could alter social roles. Such dis-tress not only calls forth caretaking but also obtains the sick role for those with acute illness. This social role with its privileges and responsibilities protects society from the disruptive effects of illness and promotes the return to health and social functioning of its members. Persons who are socially isolated or lacking in social support are more likely to manifest care-eliciting behaviour such as hypochondriasis.
Physicians  play an important role in the development of hypo-

chondriasis. They may make alarming statements or fail to provide reassurance that is based on thorough evaluation. In addition, they may order unnecessary tests, diagnose undetected disease, or treat injudiciously. They may add to concerns by failing to diagnose the psychiatric disturbance—hypochondriasis—telling patients instead that nothing is wrong. In doing this, they challenge and reject patients thereby contributing to suffering and alienation from the health care system.
Cultural attitudes  may contribute to hypochondriasis. The 
American lifestyle, which emphasizes ﬁ  tness and attractiveness, 
fosters preoccupation with health and encourages people to see their distress in terms of physical illness. There are, for example, cultural differences in the threshold for pain, pain tolerance, patterns of arousal, and physiological and behavioural responses to pain.
Course

Course
Hypochondriasis may begin at any age including childhood. The onset may be associated with stressful life events that in some instances involve illness. Some individuals develop hypo-chondriacal concerns transiently and others lastingly in reaction to physical illness. Among family medicine patients, those who became hypochondriacal a year after initial assessment were found to have had more illness worry and unexplained symptoms and to have rated their health as worse at baseline than non-hypochon-driacal patients. Ambiguous symptoms or illness events may con-tribute to hypochondriacal concerns in patients so predisposed. Hypochondriasis appears to follow a chronic, ﬂ  uctuating course.
Outcome
Follow-up studies show that, after their initial clinic visit, most 
patients with hypochondriasis improve. Still, a substantial propor-tion continue to meet criteria for the disorder and many more have

patients with hypochondriasis improve. Still, a substantial propor-tion continue to meet criteria for the disorder and many more have 
persisting symptoms. For instance, among hypochondriacal general medicine patients, Noyes et al .
(12) and Barsky et al .(13)
found that, after 1 to 4 years, two-thirds continued to qualify for 
the diagnosis and the remaining one-third had persisting symp-toms. Thus, despite improvement, the patients continued to be more hypochondriacal, more impaired, and more symptomatic than non-hypochondriacal patients.
Like patients in general, those with hypochondriacal concerns 
tend to seek care when they are most distressed. Their subsequent improvement may represent a natural ﬂ  uctuation, a response to 
physician contact or to non-speciﬁ  c treatment. Some patients

physician contact or to non-speciﬁ  c treatment. Some patients 
report having responded to reassurance. In a few instances, serious medical illness may relieve hypochondriacal concerns by legitimiz-ing symptoms.Studies indicate that greater severity and longer duration of 
symptoms are predictive of worse outcome. Failure to remit in one or more follow-up studies was predicted by more severe hypochon-driacal concerns and somatic symptoms, longer duration of hypo-chondriasis, more psychiatric comorbidity, poorer perception of health, and greater neuroticism.

There is little information concerning complications of hypochon-driasis. Because some patients utilize extensive medical care, one might expect complications resulting from repeated or unneces-sary evaluations, tests, procedures, or treatments. Such iatrogenic complications have been reported for somatoform disorders but there is little documentation for hypochondriasis. On the other hand, physical illness may be overlooked in patients whose prob-lems are considered psychiatric. There is almost no information on mortality. Suicide is said to be rare in hypochondriasis unless accompanied by severe depression in which case the risk may be increased.
Treatment

Treatment
Until recently, the treatment of hypochondriasis was regarded with pessimism. It now appears that effective psychological, even pharmacological, interventions are being developed. A variety of approaches have been proposed but controlled trials of cognitive-behavioural therapy have established its efﬁ  cacy, and preliminary 
trials of antidepressant medication have shown promise.
Psychological therapies
Most hypochondriacal patients, referred to mental health pro-fessionals, receive psychotherapy  although such treatment has 
received little study. In one controlled trial a small number of patients with hypochondriasis were randomly assigned to explana-
tory therapy or a waiting list. The therapy yielded signiﬁ  cant

tory therapy or a waiting list. The therapy yielded signiﬁ  cant 
improvement in illness behaviour and health care utilization com-pared to no treatment, and gains were maintained for 6 months. This form of therapy involves repeated physical examinations, reassurance concerning symptoms, and information about psycho-physiologic processes. Additional controlled trials of this and other forms of psychotherapy (e.g. psychodynamic, interpersonal) are clearly needed.
Four randomized, controlled trials for patients with hypo-
chondriasis have shown that cognitive behavioural therapies
are superior to no therapy with benefits sustained for up to 12 months.
(32–35)  These trials show that psychological treatment is 
efﬁ cacious for referred patients. However, one study showed that 
behavioural stress management, a non-speciﬁ  c intervention, was

behavioural stress management, a non-speciﬁ  c intervention, was 
effective as well,(33) and another showed that cognitive and behav-
ioural procedures, by themselves, were equally effective.(34)
Cognitive procedures include identifying and challenging 
dysfunctional thoughts and formulating more realistic beliefs. Behavioural procedures involve exposure in vivo  with response 
prevention. These techniques include exposure to feared internal and external stimuli (e.g. physical exercise, visiting sick persons, reading about feared diseases, writing one’s obituary) and preven-tion of checking and reassurance-seeking behaviours.
These trials showed that psychological treatment is effective but 
leave important questions unanswered. For instance, is psychological

1027
therapy acceptable to most hypochondriacal patients in primary 
care? Are the techniques speciﬁ  c or do the beneﬁ  ts result from 
non-speciﬁ  c factors (e.g. therapeutic attention, therapist–patient 
relationship, credible procedures)? Also, are these treatments cost-effective? One trial involved up to 16 sessions over 4 months, which is expensive in terms of time and resources.
In consideration of these issues, several authors have advocated 
agroup approach . For example, one study showed that group 
treatment is feasible. T o improve acceptance, the authors referred to their intervention as a course in stress management and carried it out in a general practice setting.
Pharmacological therapies
There is evidence that patients with secondary hypochondriasis respond to drug therapy for the primary disorder. For example, Noyes et al .
(36) assessed hypochondriacal concerns in patients

(36) assessed hypochondriacal concerns in patients 
receiving pharmacological treatment for panic disorder and agora-phobia. At the completion of treatment, a signiﬁ  cant reduction in 
concerns was observed among those whose anxiety symptoms had improved. Observations of a similar kind have been made in patients with major depression.
No randomized controlled trials of pharmacotherapy for hypo-
chondriasis have yet been completed, but a series of open label studies suggest that medication has promise. For example, Fallon et al.
(37) reported that 10 or 16 patients with primary hypochon-
driasis given ﬂ  uoxetine were very much improved after 12 weeks. 
And others have reported similar results with paroxetine, ﬂ  uvox-

amine, and nefazodone. Of the more than 50 patients enrolled in these trials, two-thirds responded to an SSRI. In these trials, drugs were relatively well tolerated and few patients dropped out because of side effects. This is noteworthy in view of the sensitivity to adverse effects observed in such patients. Controlled trials are needed to show proof of efﬁ  cacy in primary hypochondriasis.
Most hypochondriacal patients are best managed by their primary 
physicians. Few are successfully referred for specialty care because the focus of their concerns is, at least initially, on unexplained somatic symptoms. Although for some the ultimate goal is speciﬁ  c 
treatment, such treatment is not yet widely available.
Successful management depends upon a trusting relationship

Successful management depends upon a trusting relationship 
with a physician. T o establish this, the physician should ﬁ  rst legiti-
mize the patient’s symptoms  by listening carefully and completing 
a thorough evaluation. Respectful treatment and statements to the effect that unexplained symptoms are nonetheless real are often 
helpful (see Table 5.2.5.4).
The scheduling of regular visits  is an important strategy. Such 
visits serve several purposes. First, they reduce the reward for more severe or new symptoms that patients often present at unscheduled 
calls or visits. Next, they assure patients that the physician has an ongoing interest in their well-being. Finally, they provide reassur-ance through continued health monitoring.
Physicians should use restraint in evaluating  hypochondriacal

Physicians should use restraint in evaluating  hypochondriacal 
patients. New symptoms must be thoroughly evaluated, but overly aggressive diagnostic evaluation can be counterproductive. Extensive and dramatic tests can generate alarm, and when testing is repeated, it may convey physician uncertainty. Physicians should also avoid making diagnoses simply to have something to treat.
Physicians should also approach treatment cautiously .
Medications, even when prescribed for benign indications, cause patients to worry about the conditions for which they are given. And too often they result in intolerable side effects and iatrogenic 
complications.
Hypochondriacal patients need an explanation for their dis-
tress , one that counters the notion of serious disease. Patients may 
be told their problem lies in the central nervous system processing of bodily sensations; this means they have a sensitive nervous system that ampliﬁ  es discomforts and dysfunctions. Such an expla-

nation gives legitimacy to the problem and avoids the stigmatizing label of hypochondriasis. Alternatively, patients may be told that they suffer from excessive health anxiety or worry. An explanation of the role of anxiety in altering attention, amplifying bodily sensations, and generating physiological symptoms may also be acceptable.
The goal of medical management is not to remove symptoms 
but help patients cope with them. The expectations of patients seeking elimination of symptoms may need to be modified. Reduced dependence on the technical aspects of care (namely, diagnostic testing and corrective intervention) is an important aspect of this overall objective. Patients need assistance in manag-ing their lives so as to minimize continuing symptoms. The aim is

improved functioning , a greater sense of control, and improved 
self-esteem. These objectives may accompany a gradual return to work and meaningful activity, and may be enhanced by improve-ments in exercise, diet, and daily routine.
Developing and maintaining a therapeutic relationship  with 
the hypochondriacal patient is often challenging. The patient may be mistrustful and feel that his or her suffering is not understood. Masochistic and obsessional personality traits may contribute to a 
difﬁ cult doctor–patient relationship. A patient with such traits 
may seek mistreatment and thwart the physician’s attempts to be helpful. Y et, a positive relationship is the key to successful management and can be achieved with acceptance, empathy, and understanding.
(38)
Speciﬁ  c treatment
Many hypochondriacal patients have psychiatric comorbidity,

(38)
Many hypochondriacal patients have psychiatric comorbidity, 
and treatment of comorbid anxiety and depressive disorders may yield significant improvement. If hypochondriasis has arisen during the course of an anxiety or depressive disorder, then suc-cessful treatment of the primary disorder may bring remission of hypochondriacal symptoms.
Speciﬁ  c treatments, to be acceptable, must be available in the 
primary care setting. Treating professionals must let patients know that their concerns are legitimate and their suffering understood. Beyond this, they must place a premium on engaging the patient, techniques for which have been described by a number of authors.Table 5.2.5.4  Management strategies for patients with 
Legitimize the patient’s symptoms
Establish a regular schedule of visits
Base diagnostic evaluation on objective ﬁ  ndings

Approach treatment of physical symptoms cautiouslyProvide a plausible explanation for symptomsEstablish a goal of improved functioning5.2.5 hypochondriasis (health anxiety)

SECTION 5  psychiatry and medicine 1028
These patients are prone to drug side effects and often discon-
tinue medication. For this reason, initial doses should be small, with gradual increases according to a modiﬁ  able schedule. Treating 
physicians should acknowledge the patient’s sensitivity, and indicate that side effects are likely but may be dealt with.
Hypochondriasis is a signiﬁ  cant medical condition for which 
treatment is now available.
Asmundson, G.J.G., Taylor, S. and Cox, B.J. (eds.) (2001). Health anxiety: 
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perspectives on an ancient malady . Oxford University Press, New Y ork.
Taylor, S. and Asmundson, G.J.G. (2004). Treating health anxiety: a 
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1029
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5.2.6. Pain disorder
Persistent somatoform pain  disorder is an ICD-10 diagnosis, 
which is included in the group of somatoform disorders. The term pain disorder  is used in DSM-IV , and for convenience that is the 
term used here to refer to both classiﬁ  cations, unless a distinction

term used here to refer to both classiﬁ  cations, unless a distinction 
needs to be made. This chapter aims to clarify the relationship of pain to mental disorders, the diagnosis of pain disorder and its dif-ferential diagnosis, and then considers how psychosocial factors contribute to pain, the treatments that stem from them, and the psychiatrist’s potential contribution.
Pain has been deﬁ  ned by the International Association for the 
Study of Pain ( IASP ) as ‘an unpleasant sensory and emotional 
experience associated with actual or potential tissue damage or described in terms of such damage’ . ‘Pain’ is used here in this sense; it is not used primarily to indicate mental distress or anguish. As a perception, pain is essentially a subjective experience, and is directly 
accessible only to the patient. By contrast, tissue damage can be

accessible only to the patient. By contrast, tissue damage can be 
assessed by others, and its relationship with the subjective charac-teristics of pain have been shown to be variable, modulated by social and cultural experience, as well as within the central and peripheral nervous system.
Pain and the psychiatrist
Psychiatrists are likely to see patients with pain in psychiatric, gen-eral hospital, and community settings. Pain is associated with a wide range of mental disorders, and there are different ways in which this relationship may arise.
Pain may contribute to the cause of a mental disorder; for exam-
ple, when a patient with cancer has pain, which is unrelieved by analgesics, and becomes depressed. This can result in additional distress and disability, and subsequently an exacerbation of pain. Treatment of depression may contribute to the relief from pain and improve the quality of life.
In a general hospital psychiatrists may see patients with acute

In a general hospital psychiatrists may see patients with acute 
pain , like the patient described above, but more often will see 
patients with chronic pain . Whatever the initial cause, the longer 
pain persists the more likely is it to result in the development of 
inappropriate patterns of illness behaviour and to have a pro-
found effect on relationships with the family and other carers, presenting more complex challenges for management and poorer prognosis.Pain disorder
Diagnostic and clinical features
Persistent somatoform pain disorder  in ICD-10  is the only 
somatoform disorder that is essentially characterized by pain. The diagnostic requirements  are as follows:
1 ‘persistent, severe, and distressing pain’;
2 pain ‘cannot be explained fully by a physiological process or a 
physical disorder’;
3 ‘pain occurs in association with emotional conﬂ  ict or psychoso-
cial problems that are sufﬁ  cient to allow the conclusion that they 
are the main causative inﬂ  uences’ .

There are also likely to be many of the features that occur in the 
other somatoform disorders, which have been described in previ-ous chapters. The pain can be localized, as in low back pain, or gen-eralized, as in ﬁ  bromyalgia.
In ICD-10 , the diagnosis is excluded if pain, presumed to be 
mainly psychological in origin, occurs in the course of schizophre-nia or depressive disorder, or is believed to be due to psychophysi-ological mechanisms such as muscle tension. The main differential 
diagnosis , according to ICD-10, is the histrionic elaboration of

diagnosis , according to ICD-10, is the histrionic elaboration of 
pain primarily due to organic causes, particularly if this has not yet been diagnosed. In practice, it is uncommon for pain that has been properly investigated, and has persisted for more than 6 months, to be found subsequently to have a speciﬁ  c organic cause.
The DSM-IV  diagnosis of ‘ pain disorder ’ also needs to be con-
sidered because the requirements for diagnosis and the underlying rationale are rather different. This diagnosis is divided into three subtypes :
1 ‘Pain disorder associated with psychological factors ’ , in which 
psychological factors are judged to play the major role, and phys-ical disorders play either no part or only a minor part in its onset or maintenance.
2 ‘Pain disorder associated with both psychological factors and a 
general medical condition ’ , in which both psychological proc-
esses and an organic disorder are judged to make important con-tributions to causation.

3 ‘Pain disorder associated with a general medical condition ’,  d u e  
to an organic disorder and in which psychological factors are judged to make no contribution or to play only a minor role. This subtype is not regarded as a mental disorder but is coded on Axis III.
For the ﬁ  rst two subtypes the diagnostic criteria, all of which 
must be satisﬁ  ed, are summarized as follows:
(a) Pain, localized or more general, is the predominant symptom 
and its severity warrants clinical attention
(b) Pain results in distress, and impairment in social, occupational, 
or other areas of functioning.
(c) Psychological factors are judged to have an important role in 
the onset, severity, exacerbation, or maintenance of pain.
(d) It is not intentionally produced or feigned (factitious disorder 
and malingering are speciﬁ  cally excluded).

(e) P ain is not better accounted for by a mood, anxiety, or 
psychotic disorder and does not meet criteria for dyspareunia.5.2.6 pain disorder

SECTION 5  psychiatry and medicine 1030
Pain disorder can also be coded according to whether it is acute 
or chronic (less or more than 6 months duration).
Comparison of ICD-10 and DSM-IV
The diagnoses of pain disorder in ICD-10 and DSM-IV share a number of characteristics. Pain disorder should be diagnosed as a mental disorder if psychological factors are thought to make a  signiﬁ  cant contribution to predisposition, precipitation, or main-
tenance, or to the severity of pain. In ICD-10, there should be evi-dence that emotional conﬂ  ict or psychosocial problems are the 
main ‘causative inﬂ  uences’ , whereas in DSM-IV psychological fac-
tors are judged to play either the ‘major role’ or ‘an important role’ . In both, the diagnosis can be made even though there may be pos-sible or deﬁ  nite evidence of an organic disorder that contributes 
to pain (for instance, a prolapsed intervertebral disc), provided that this is judged to be insufﬁ  cient to account fully for the fea-

tures of pain. Both classiﬁ  cations stress the severity of pain and 
the distress caused by it, but only DSM-IV speciﬁ  cally requires a 
degree of disability as a diagnostic feature. The implication is that diagnosis requires detailed physical and psychiatric evaluation, including an assessment of the family and social context, as well as of disability.
Differential diagnosis of pain disorder
Pain can occur in the setting of virtually any mental disorder. Table 5.2.6.1 lists the ICD-10 diagnoses and their DSM-IV equiva-lents in which pain may be a predominant feature. The general description of most of these disorders is provided in other chapters of this book and the following account focuses only on aspects relevant to pain.
(a) Organic disorders

Many painful disorders have a well-recognized organic pathology that accounts for the occurrence of pain (for example, angina, sickle cell arthropathy), but psychosocial processes tend to modify the severity of pain and associated disability. Thus, psychological and social interventions may make an important contribution to management, and as pain becomes more chronic, or fails to respond to usually effective physical treatments, psychosocial interventions assume greater signiﬁ  cance. These disorders can be diagnosed in 
ICD-10 within the diagnoses headed ‘ Psychological interactions 
with physical disorders ’ in Table 5.2.6.1.
(b) Pain syndromes of uncertain origin
There are many disorders characterized by pain, which are essen-
tially syndromes with no known consistent organic pathology (Table 5.2.6.2). Psychological and social factors are thought to contribute to the development and maintenance in many cases,
(1)

(1)
but psychological causes speciﬁ  c to these different syndromes have 
not been identiﬁ  ed. Patients with these pain syndromes tend to 
have a greater prevalence of non-psychotic mental disorders than is found in the general population. The pain itself can usually be accommodated in ICD-10 within the categories of somatoform 
autonomic dysfunction  or somatoform pain disorder  (see below). 
The ‘diagnoses’ listed in Table 5.2.6.2 tend to be used by non-psychiatrists to describe clusters of medically unexplained symp-toms and are terms which are likely to be acceptable to patients. Treatments for these disorders generally include physical approaches, often of limited efﬁ  cacy, as well as a range of psychosocial interven-
tions, which are described below.(c) Pain and mental disorders
(i) Psychoses

At the beginning of the twentieth century, French psychiatrists described coenestopathic states  as disorders characterized by 
unpleasant sensations, particularly pains, thought to be of central 
origin, but unrelated to organic brain disease.
(2) Such disorders 
were a daily occurrence in psychiatric clinics, commonly associated with the psychoses, and in this setting were related to somatic 
hallucinations  and systematized delusional states . Such pre-
sentations are now described infrequently in Europe and North America.
Patients with any psychosis may complain of pain, sometimes 
with bizarre descriptions of quality and delusional attribution . In 
practice, it is difﬁ  cult to differentiate between a somatic hallucina-
tion  and an illusion (arising from physiological or pathological

tion  and an illusion (arising from physiological or pathological 
processes). Complaints of pain in psychotic disorders have no psy-chiatric diagnostic speciﬁ  city. Pain has been described particularly 
in association with schizophrenia and depressive psychoses, but may occur in any psychotic disorder. In the course of a psychotic disorder, illusions and delusional interpretations of pain may arise from unrelated organic disorders and therefore require careful physical assessment .
(ii) Mood- and anxiety-related disorders
These are by far the most common mental disorders associated 
with pain in most settings. In the general population, 12 per cent of adults have experienced chronic widespread pain  (deﬁ  ned accord-
ing to the criteria of the American College of Rheumatologists) in the previous 3 months and their prevalence of mental disorders is three times that of the pain-free population.

(3) Most of these diag-
noses are mood and anxiety disorders, with the former being more common in those with chronic pain. In pain clinic settings , the 
prevalence of mental disorders varies according to referral patterns, but about 30 to 40 per cent of patients have depressive disorders, and this is similar in those with and those without a relevant physi-cal disorder.
(4) Those without organic disorders tend to have lower 
ratings for both mood disorders and pain severity. Those with mood disorders report more severe pain.
Diagnosis of mood and anxiety disorders is based on the usual 
standardized criteria, but may be missed due to the process of somatization , particularly where patients attribute their depressed

standardized criteria, but may be missed due to the process of somatization , particularly where patients attribute their depressed 
mood to pain and an underlying physical condition (whether present or not) and invite their doctors to share this belief.
(5) In the 
past, pain has been thought of as a proxy for depression, giving rise to the concept of a ‘ depressive equivalent ’ or ‘ masked depression ’.  
This has been based mainly on evidence for the psychogenicity of chronic pain rather than a speciﬁ  c relationship to depressive 
disorders, has received widespread criticism, and has not advanced theoretical knowledge or clinical practice.
(iii) Post-traumatic stress disorder

Many patients with post-traumatic stress disorder (PTSD) have been subjected to actual or threatened physical injury, so it is not surprising that pain is one of the commonest symptoms that they report, the prevalence ranging from 20 to 80 per cent. Further, 10 to 50 per cent of patients with chronic pain satisfy criteria for PTSD, and patients with musculoskeletal pain are four times more likely to develop PTSD than those without it.
(6)Pain disorder and 
PTSD  can be diagnosed jointly, if criteria for both are satisﬁ  ed. 
Mechanisms including shared vulnerability, fear-avoidance, and

1031
mutual maintenance have been postulated to account for this 
comorbidity.(7) This has implications for assessment (described 
below), and treatment programmes may need to be modiﬁ  ed 
accordingly.
(iv) Somatoform disorders
Somatoform disorders are uncommon in people with chronic pain in the general population.
(3) Prevalence varies considerably in clin-
ical samples, but somatoform disorders have been reported in 12 to 52 per cent of patients,
(4) so they include highly selected samples.
Complaints of pain occur commonly in each of the somatoform 
disorders and may be the predominant symptom. Multiple physical 
complaints, often including pains at different sites, ﬂ  uctuate from 
time to time usually for many years, providing a characteristic feature of somatization disorder . In hypochondriacal disorder
pain is a common complaint, and forms the focus for concern and overvalued beliefs about unidentiﬁ  ed disease.
The diagnosis of somatoform autonomic disorder  is based on

The diagnosis of somatoform autonomic disorder  is based on 
autonomic arousal (palpitation, sweating, tremor), which must be a prominent feature of the clinical picture, together with physical 
complaints, often pain, referred to speciﬁ  c organs, systems, or parts 
of the body. As with other somatoform disorders, the patient will 
be distressed about the possibility of underlying physical disease 
and is not reassured by negative ﬁ  ndings on appropriate assess-
ment and explanation. This diagnosis is sometimes appropriate for syndromes listed in Table 5.2.6.2.
Pain, as a form of conversion , has a traditional place in the liter-
ature on hysteria , based on the concepts of psychogenicity, the Table  5.2.6.1  Mental disorders included in the differential diagnosis of pain disorder
Psychotic disorders
F00–09  Organic mental disorders

F20–29  Schizophrenia, schizotypal, and delusional disorders290      Dementia 293 Delirium
273      Schizophrenia and other psychotic disorders
Mood- and anxiety-related disorders
F32/33    Depressive episodeF34.1   Dysthymia
F41      Anxiety disorders
F43.1   Post-traumatic stress disorderF43.2   Adjustment disorders296.2/3     Major depressive disorder
300.4     Dysthymic disorder
300.02     Generalized anxiety disorder
309.81     Post-traumatic stress disorder309      Adjustment disorders
F44.4   Dissociative (conversion) disorders
F45.0   Somatization disorder
F45.1   Undifferentiated somatoform disorder
F45.2   Hypochondriacal disorderF45.3   Somatoform autonomic dysfunction
F45.4   Somatoform pain disorder
F45.8   Other somatoform disordersF45.9   Somatoform disorder, unspeciﬁ  ed300.11     Conversion disorder
300.81     Somatization disorder
300.81     Undifferentiated somatoform disorder

300.7     Hypochondriasis300.8       Pain disorder
300.81     Somatoform disorder NOS
Other neurotic disorders
F48.0   Neurasthenia
F48.8   Other speciﬁ  ed neurotic disorders (occupational neurosis, e.g. writer’s cramp)
Sexual disorders
F52.5   Non-organic vaginismus
F52.6   Non-organic dyspareunia306.51       Vaginismus
302.76      Dyspareunia
Psychological interactions with physical disorders
F54       Pyschological or behavioural factors associated with disorders or diseases classiﬁ  ed 
 elsewhere
F68.0   Elaboration of physical symptoms for psychological reasons316       Psychological factors affecting medical 
 condition
Disorders of behaviour
F68.1   Intentional production or feigning of symptoms 300.19     Factitious disorder
V65.2    Malingering
Comorbidity of pain disorder

condition
Any of the above except psychoses and other somatoform disorders
Substance abuse
F10      Disorders due to alcoholF11–13   Disorders due to psychoactive substance abuse
F55      Abuse of non-dependence-producing substances291 & 303.9    Alcohol-induced disorders and dependence
292 & 304     Other substance-induced disorders and 
 dependence
F60–62  Personality disorders and changes 301       Personality disorders5.2.6 pain disorder

SECTION 5  psychiatry and medicine 1032
contribution of stressful experiences with dissociation, and primary 
gain. In recent years, however, research has focused on other psychological processes, and the concept of conversion as a primary mechanism now seems to be of limited interest. The category of dissociative (conversion) disorder  in ICD-10 speciﬁ  cally includes 
sensory loss but excludes pain (sensory ampliﬁ  cation), which 
therefore should not be diagnosed as a dissociative disorder. DSM-IV also excludes pain from the diagnosis of conversion disorder, unless other diagnostic criteria are satisﬁ  ed.
The uncertain relationship and limited value of the different 
diagnoses included within the group of somatoform disorders in ICD-10 have been discussed in Chapter 5.2.1, and are well illustrated by the fact that pain may be a prominent feature of each category. Somatoform disorders presenting with pain are usually diagnosed

assomatization disorder or pain disorder , with the former taking 
precedence if the diagnostic criteria are satisﬁ  ed.
Any physical or mental disorder may be diagnosed in addition 
to pain disorder. Anxiety and depression are common, and an additional diagnosis of anxiety disorder  or mood disorder  can be 
made if the criteria are satisﬁ  ed. This dual diagnosis can be useful 
if, for example, a depressive disorder develops in the presence of a long-standing pain disorder. Any temporal relationship can occur, however, with pain onset preceding, developing simultaneously with, or following the onset of a mood disorder.
Other common comorbid diagnoses include substance abuse
and dependence, sometimes of iatrogenic origin, and their manage-ment is an important component of pain-treatment programmes.
(8)
Personality disorders  are an additional category of comorbidity.

(8)
Personality disorders  are an additional category of comorbidity. 
No single disorder predominates but histrionic, narcissistic, anxious (avoidant), and dependent features are all common in clinical practice, and anankastic traits may feed an inﬂ  exible focus 
on physical illness.
Although the association of psychiatric symptoms with chronic pain has been studied in the general population, the prevalence of pain disorder, and other mental disorders presenting with pain, is uncertain because large-scale surveys of mental disorders do not include an assessment of pain and of related physical conditions.Assessment of pain
Clinical assessment
The psychiatric assessment requires a full psychiatric history  and 
mental state examination , with particular attention to those addi-
tional features relevant to pain. The pain history  should include

tional features relevant to pain. The pain history  should include 
total duration (often underestimated by the patient), a detailed inquiry about the location and distribution of pain, including direct questions aimed at a total body survey, and the timing of ﬁ  rst 
onset, subsequent periods of relapses and remissions, and their relationship to life events and difﬁ  culties. The family history
should include assessment of severe, chronic or disabling physical disorders, and the patient’s involvement with them. The personal 
history  should include adverse childhood experiences (discussed 
below) and the past history  of physical disorders and disability is 
particularly important.
Patients who somatize  will tend to deny concurrent psychosocial 
events and their signiﬁ  cance. For example, one of our patients was 
consistently unable to recall any distressing events in the year prior

consistently unable to recall any distressing events in the year prior 
to the onset of severe, persistent, and disabling headache. His wife gave an account of the deaths of his father, brother, and closest friend during that year, and moreover described him as so dis-tressed by these bereavements that he felt unable to attend any of the funerals. It is essential to take a history from other informants ,
and this can also provide an opportunity to assess the attitudes, knowledge, and beliefs of carers, and their interaction with the patient.
The patient’s pain beliefs and behaviours  (described below) are 
key aspects of the mental state examination . Patients often 
attribute chronic pain to an organic disorder and offer diagnoses; it is essential to review their medical records  to assess the clinical 
ﬁ ndings and investigations, and the extent to which they support

ﬁ ndings and investigations, and the extent to which they support 
any diagnosis which is offered. Chronic pain associated with an underlying organic disorder may be exacerbated when the patient suffers a stressful life event, so it is important to avoid assumptions 
of a dichotomy  of either ‘organic’ or ‘psychogenic’ pain .
Standardized psychometric assessments
Many standardized questionnaires have been developed for the 
assessment of patients with chronic pain. They can be valuable for identifying mechanisms that contribute to pain, planning treat-ment, and monitoring changes during and after treatment. The evaluation of pain and associated beliefs and behaviours requires measures developed speciﬁ  cally for this purpose, and these are 
described below.
Other assessments, for example of mood ,illness behaviour , and 
social dysfunction , have been developed within the ﬁ  eld of pain

social dysfunction , have been developed within the ﬁ  eld of pain 
research. Some measures are rather idiosyncratic, with uncertain psychometric properties, aimed at restricted diagnostic groups and clinical settings. This undermines the need to use consistent methods that allow comparison of different groups of patients, with physical, mental, and mixed disorders, at different places and 
times.
(a) Pain
The severity  of pain can be assessed(9) using standardized visual 
analogue scales  and numeric analogue scales . Such scales may 
have anchor points ranging from ‘no pain’ to ‘the worst possible pain’ .Table 5.2.6.2  Disorders of uncertain origin, presenting primarily 
with pain, in which psychosocial factors are thought to contribute to predisposition, precipitation, or course
Generalized
Fibromyalgia
Relatively localized
Tension headache—acute or chronic

Temporomandibular pain and dysfunction syndrome
Atypical facial painAtypical (non-cardiac) chest pain
Abdominal pain of psychological origin
Non-ulcer dyspepsia
Irritable bowel syndrome
Chronic pelvic painIrritable bladder syndrome
Procatalgia fugax

1033
The quality  of pain can be assessed with verbal descriptor 
scales .(9) Factor analysis has resulted in the emergence of two 
that have best survived the test of time: an ‘ affective ’dimension
(represented by words such as exhausting, terrifying, vicious), and a ‘sensory ’dimension  (e.g. stabbing, crushing, burning). They 
have been found consistently when administered in different languages and to different cultural groups. Ratings on both these scales are positively correlated with pain severity and mood ratings and, in the presence of mental disorders, contribute little to diagnosis.
The topographical distribution of pain  can be assessed by using

The topographical distribution of pain  can be assessed by using 
outline drawings of the body (front, back, and sometimes sides), which the patient is asked to shade to indicate the distribution of pain. These can help to identify pain that does not conform to physiological distributions and also widespread pain. Measures of pain intensity, quality, and distribution can be used toget her to capture the rather elusive and entirely subjective experience of pain.
(b) Pain behaviours
Although the experience of pain is entirely personal, it may be communicated to others by a range of verbal and non-verbal behaviours, which in some cases may be maladaptive, and which in turn inﬂ  uence the responses of others. Using a learning theory 
model , Fordyce
(10) classiﬁ  ed all pain into ‘operant’ and ‘non-
operant’ pain . The former includes all pain that is modiﬁ  ed by

operant’ pain . The former includes all pain that is modiﬁ  ed by 
positive or negative reinforcement, whether or not organic pathol-ogy is present. Standardized structured assessments  are available 
to measure a range of well-deﬁ  ned behaviours .
(11) These may 
include complaints of pain, requests for medication, groaning, facial expression, restricted mobility and the use of aids, time spent resting, and postures such as guarding and bracing. Such behav-iours have been shown to ﬂ  uctuate in response to changes in the 
environment, including different attitudes and responses of 
carers . This has led to the assessment of pain behaviours and their 
environmental reinforcers , and the development of pain-treatment 
programmes that originally focused on behavioural change by modifying reinforcement. Recent interest has focused on pain-
related fears  (e.g. of exacerbating pain by injury) and the manage-

ment of consequent avoidance .
(12)
(c) Pain beliefs
The belief that chronic as well as acute pain signals an underlying 
physical disease, which requires and should respond to physical intervention, whilst avoiding usual activities and functions, con-tributes to the development and maintenance of chronic pain and non-adherence to treatment, and the widespread dissatisfaction often expressed by patients and their doctors. Inappropriate beliefs that are relevant to pain assessment fall into three groups
(13):
1 beliefs about the nature of reality—for example, ‘life should be 
pain-free’;
2 beliefs in response to challenging circumstances, such as pain—
including locus of control ,attributional style ,cognitive errors ,
and coping strategies ;

3 speciﬁ  c ideas about the cause of a pain, appropriate manage-
ment, and outcome.
The questionnaire assessment of pain-related beliefs has assumed 
increasing importance in the ﬁ  eld of pain research,(13) with the recognition that pain beliefs interact with pain, cognitions, 
behaviours, affects and disability, and contribute to the prediction 
of outcome. Thus cognitive approaches to treatment are often inte-grated with behavioural management.
Psychosocial contributions to the 
development of pain
The origins of chronic pain are, in several respects, similar to those 
of somatization and other somatoform disorders. Current models of causation involve the interaction of biological, psychological, and social factors, each contributing to predisposition, precipita-tion, and maintenance.

The family and personal histories  of patients with chronic pain 
include an excess of mood disorders, pain and disability, substance abuse, and personality disorders. Engel
(14) described the dynamics 
of ‘the pain prone patient ’ involving abusive childhood experiences, 
and noted how pain can become a pathway for the expression of guilt and expiation. Recent research
(15) has reconsidered the signiﬁ  -
cance of reports of physical and sexual abuse  and other adverse 
childhood experiences . The relationship between chronic pain in 
adults and these childhood experiences appears, at least to some extent, to be determined by selective reporting , particularly in 
those with associated mental disorders,
(16) but these experiences 
may make a signiﬁ  cant contribution to pain in some individuals.
Precipitation of chronic pain is, in effect, transition from acute 
to chronic pain , and factors associated with this transition(17,18)

include current mood and anxiety disorders, negative life events 
including physical illnesses and trauma, the social support network and dissatisfaction with work. A population based prospective study
(19) found that new episodes of chronic widespread pain were 
predicted by the number of previous non-pain somatic symptoms and by a measure of illness behaviour which assessed numbers of consultations, treatments and perceived disability, and these two measures had an additive effect. Recent research has indicated the potential value of interventions designed to prevent the progression from acute to chronic pain.
(17,18)
The psychiatric and psychological 
management of pain
Treatment of mental disorders
The treatment of chronic pain has presented a challenge to the

(17,18)
The treatment of chronic pain has presented a challenge to the 
ingenuity of health professionals, particularly because no single specialty or profession has the range of skills that is required. The treatment of mental disorders,
(5) such as depressive or anxiety 
disorders,(20) is similar in most respects, whether or not pain is a 
prominent feature. In the presence of pain, however, mental disor-ders tend to be missed, and when recognized are treated inade-quately. Depressive disorders with features indicating a good response to antidepressants  should be treated with full therapeutic 
doses, but not with narcotics .Anxiolytic drugs  including benzo-
diazepines , which result in dependence, should not be used in the 
treatment of these chronic disorders.
The use of antidepressants for pain relief

Antidepressant drugs are often used for the treatment of pain in patients who are not depressed. Randomized controlled trials
(21)
indicate that antidepressants, in doses within the usual therapeutic 5.2.6 pain disorder

SECTION 5  psychiatry and medicine 1034
range, provide more effective analgesia  than placebo preparations 
in the treatment of diabetic neuropathy, postherpetic neuralgia, and atypical facial pain, as well as chronic non-malignant pain. Different tricyclic antidepressants  (TCAs) appear to be equally 
effective and are more effective than selective serotonin-reuptake 
inhibitors . Data on seretonin noradrenaline-reuptake inhibitors
are increasing and suggest that they may be effective, and preferable to TCAs because of a superior side effect proﬁ  le.
(22) The analgesic 
effect of antidepressants occurs in patients who are not depressed and is independent of any antidepressant effect.
Psychological treatments(5,23) are derived from different theoretical 
formulations of the aetiology of chronic pain. These include behav-ioural, cognitive, and psychodynamic approaches. Reviews of ran-domized controlled trials of behavioural and cognitive approach-
es

es
(24) that have been developed speciﬁ  cally for the treatment of 
chronic pain illustrate the problems in assessing outcome due to different sampling methods, different types of control groups, non-standardized treatment components, and the different assessments that are included. Despite these limitations, the best studies demonstrate that these treatments are more effective than ‘usual’ medical treatment, remaining on a waiting list, or exercise programmes, and improvements can be sustained during lengthy follow-up periods.
Other approaches include various forms of ‘stress management’ 
including relaxation techniques ,biofeedback , and hypnosis .
Their value is uncertain; although pain ratings tend to be reduced, this is not a consistent ﬁ  nding on all measures.

Psychological treatments are rarely used in isolation, either 
from each other or from additional interventions, and integrating 
different approaches may enhance their effects.
(23)
Multi-disciplinary pain management clinics
Pain-treatment centres(25) have been established in many coun-
tries and provide a diverse range of professional skills, treatments, and models of service delivery. In some, management is based mainly on anaesthetic techniques and medication, but psychologi-cal approaches are provided in others by clinical psychologists  and 
nurse therapists . The management of problems due to inappropri-
ate medication and substance abuse  is an essential component of 
treatment.
(8) Many clinics offer structured programmes  of educa-

tion and rehabilitation, with increments of exercise , to overcome 
disability , rather than aiming primarily at pain relief, and to which 
physiotherapists or occupational therapists  may contribute. There 
is often an emphasis on the patient assuming increasing responsi-bility, rather than maintaining dependence on medical services .
Direct input from psychiatrists  is variable and some centres 
speciﬁ  cally exclude the treatment of patients with serious mental 
disorders because their response to treatment is less certain. Although it is well recognized that social and environmental fac-tors contribute to chronic pain problems, and can undermine progress following treatment, few specialized centres involve carers
routinely in treatment or offer family therapy .

A range of physical, psychological, and social approaches should 
be offered, based on an individual structured assessment  of needs. 
Members of the multi-disciplinary team require speciﬁ  c training
in the management of pain. The work of the team has to be carefully coordinated, both within the team and with other health 
professionals, to avoid any ambiguity concerning the methods and goals of treatment.
Many pain clinics provide a treatment package in which cognitive 
therapy and graded exercise are predominant features. A similar approach is used for a number of other conditions, including 
somatization disorder ,hypochondriacal disorder ,ﬁ bromyalgia ,
and chronic fatigue , but the extent to which they may have similar 
origins and outcomes is uncertain.
Effects of treatment
The outcome of psychological and psychiatric treatment  has been 
studied extensively,(5,24) but is difﬁ  cult to evaluate because reports

studied extensively,(5,24) but is difﬁ  cult to evaluate because reports 
differ with regard to the characteristics of patients and disorders, inclusion criteria, assessments, and treatments as well as details of treatment delivery, attrition rates, choice of control groups, and the duration of follow-up. Many patients with chronic pain are unwill-ing to accept treatment and others are considered unsuitable. Nevertheless, psychological and rehabilitation treatments can have a sustained effect, based on the range of assessments that have been described. In addition, they can result in reductions in sickness 
and beneﬁ  t payments ,
(26) return to work(27) and reduced use and 
costs of medical services .(28)
The outcome for patients with different mental disorders has not 
been assessed systematically. Patients involved in seeking compen-

sation  tend to have a poorer outcome, even after litigation  has 
been concluded, but they can also beneﬁ  t from treatment. There is 
some evidence that secondary prevention  programmes may help 
to avoid the transition from acute to chronic pain in those who are particularly vulnerable.
For more information on the topic of this chapter, we have marked with an 
asterisk (*) those references, which will be of particular interest to the reader.
 1. *Kellner, R. (1991). Psychosomatic syndromes and somatic symptoms .
 2. Dupré, E. (1913). Les cénestopathies . Reprinted as: Coenestopathic 
states. In Themes and variations in European psychiatry  (eds. S.R. Hirsch 
and M. Shepherd), pp. 385–94. John Wright, Bristol, 1974.

 3. Benjamin, S., Morris, S., McBeth, J., et al. (2000). The association 
between chronic widespread pain and mental disorder. Arthritis and 
Rheumatism ,43, 561–7.
 4. Benjamin, S., Barnes, D., Berger, S., et al. (1988). The relationship of 
chronic pain, mental illness and organic disorders. Pain ,32, 185–95.
 5. Benjamin, S. and Main, C.J. (1995). Psychiatric and psychological 
approaches to the treatment of chronic pain: concepts and individual treatments. In Treatment of functional somatic symptoms
(eds. R. Mayou, C. Bass, and M. Sharpe), pp. 188–213. Oxford University Press.
 6. Asmundson, J.G., Coons, M.J., Taylor, S., et al. (2002). PTSD and 
the experience of pain; research and clinical implications of shared vulnerability and mutual maintenance models. Canadian Journal of 
Psychiatry ,47, 930–7.

 7. *Otis, J.D., Keane, T.M., and Kerns, R.D. (2003). An examination of the 
relationship between chronic pain and post-traumatic stress disorder. Journal of Rehabilitation Research and Development ,40, 397–406.

1035
 8. British Pain Society. (2006). Pain and substance misuse: improving the 
patient experience . British Pain Society, London.
 9. *Williams, A.C.deC. (2004). Assessing chronic pain and its impact. 
In Psychosocial aspects of pain: a handbook for healthcare professionals, 
progress in pain research and management , Vol. 27 (eds. R.H. Dworkin 
and W.S. Breitbart). IASP Press, Seattle.
10. Fordyce, W.E. (1985). The behavioural management of chronic pain: a 
response to critics. Pain ,22, 113–25.
11 Keefe, F.J. and Williams, D.A. (1992). Assessment of pain behaviours. In 
Handbook of pain assessment  (eds. D.C. Turk and R. Melzack), 
pp. 277–92. Guilford Press, New Y ork.
12 De Jong, J.R., Vlaeyen, J.W.S., Onghena, P ., et al. (2005). Reduction 
of pain-related fear in complex regional pain syndrome type I: the application of graded exposure in vivo. Pain ,116, 264–75.
13. *DeGood, D.E. and Shutty, M.S. (1992). Assessment of pain beliefs,

13. *DeGood, D.E. and Shutty, M.S. (1992). Assessment of pain beliefs, 
coping and self-efﬁ  cacy. In Handbook of pain assessment  (eds. D.C. Turk 
and R. Melzack), pp. 214–34. Guilford Press, New Y ork.
14. Engel, G. (1959). ‘Psychogenic’ pain and the pain prone patient. The
American Journal of Medicine ,26, 899–918.
15. Morley, S. (2004). What impact does childhood experience have on the 
childhood development of chronic pain? In Psychosocial aspects of pain: 
a handbook for healthcare professionals, progress in pain research and 
management , Vol. 27 (eds. R.H. Dworkin and W.S. Breitbart). 
IASP Press, Seattle.
16. McBeth, J., Morris, S., Benjamin, S., et al. (2001). Associations between 
adverse events in childhood and chronic widespread pain in adulthood: 
are they explained by differential recall? The Journal of Rheumatology ,
28, 2305–9.

17. *Poleshuck, E.L. and Dworkin, R.H. (2004). Risk factors for chronic 
pain in patients with acute pain and their implications for prevention. In Psychosocial aspects of pain: a handbook for healthcare providers, 
18. *Linton, S.J. (2004). Environment and learning factors in the 
development of chronic pain and disability. In Psychological methods 
of pain control: basic science and clinical perspectives, progress in pain research and management , Vol. 29 (eds. D.D. Price and E.M. Bushnell). 
19. McBeth, J., Macfarlane, G.J., Benjamin, S., et al. (2001). Features of

19. McBeth, J., Macfarlane, G.J., Benjamin, S., et al. (2001). Features of 
somatization predict the onset of chronic widespread pain. Results of a large population based study. Arthritis and Rheumatism ,44, 940–6.
20. *Gallagher, R.M. and Verma, S. (2004). Mood and anxiety disorders in 
chronic pain. In Psychosocial aspects of pain: a handbook for healthcare 
professionals, progress in pain research and management , Vol. 27 
(eds. R.H. Dworkin and W.S. Breitbart). IASP Press, Seattle.
21. Atkinson, J.H., Meyer, J.M., and Slater, M.A. (2004). Principles of 
psychopharmacology in pain treatment In Psychosocial aspects of pain: 
a handbook for health care professionals, progress in pain research and management , Vol. 27 (eds. R.H. Dworkin and W.S. Breitbart). IASP 
Press, Seattle.
22. Sindrup, S., Otto, M., Finnerup, N., et al. (2005). Antidepressants in the 
treatment of neuropathic pain. Basic and Clinical Pharmacology and 
Toxicology ,96, 399–409.

23. *Waters, S.J, Campbell, L.C., Keefe, F.J., et al. (2004). The essence of 
cognitive-behavioral pain management. In 
Psychosocial aspects of pain: 
management , Vol. 27 (eds. R.H. Dworkin and W.S. Breitbart). IASP 
24. Morley, S., Eccleston, C., and Williams, A. (1999). Systematic review 
and meta-analysis of randomised controlled trials of cognitive behaviour therapy and behaviour therapy for chronic pain in adults, excluding headache. Pain ,80, 1–13.
25. Cohen, M.J.M. and Campbell, J.N. (eds.) (1996). Pain treatment centers 
at a crossroads: a practical and conceptual reappraisal . IASP Press, 
Seattle.26. Thomsen, A.B., Sorensen, J., and Sjogren, P . (2002). Chronic

Seattle.26. Thomsen, A.B., Sorensen, J., and Sjogren, P . (2002). Chronic 
non-malignant pain patients and health economic consequences. 
European Journal of Pain ,6, 341–52.
27. Haldorsen, E.M.H., Grasdal, A.L., Skouen, J.S., et al. (2002). Is there 
a right treatment for a particular patient group? Comparison of ordinary treatment, light multidisciplinary treatment, and extensive multidisciplinary treatment for long-term sick-listed employees with 
musculoskeletal pain. Pain ,95, 49–63.
28. Peters, L., Simon, E.P ., Folen, R.A., et al. (2000). The COPE program: 
treatment efﬁ  cacy and medical utilisation outcome of a chronic pain 
management program at a major military hospital. Military Medicine ,
165, 954–60.
5.2.7 Chronic fatigue syndrome
Chronic fatigue syndrome is a controversial condition, conﬂ  icts

Chronic fatigue syndrome is a controversial condition, conﬂ  icts 
about which have frequently burst out of the medical literature into the popular media. Whilst these controversies may initially 
seem to be of limited interest to those who do not routinely treat 
such patients, they also exemplify important current issues in med-
icine. These issues include the nature of symptom-deﬁ  ned illness; 
patient power versus medical authority; and the uncomfortable but important issues of psychological iatrogenesis.
(1,2) The subject 
is therefore of relevance to all doctors.
Fatigue as a symptom
Fatigue is a subjective feeling of weariness, lack of energy, and exhaustion. Approximately 20 per cent of the general population report signiﬁ  cant and persistent fatigue, although relatively few of

these people regard themselves as ill and only a small minority seek a medical opinion. Even so, fatigue is a common clinical presenta-tion in primary care.
(2)
Fatigue as an illness: chronic fatigue syndrome

(2)
When fatigue becomes chronic and associated with disability it is regarded as an illness. Such a syndrome has been recognized at least since the latter half of the last century. Whilst during the Victorian era patients who went to see doctors with this illness often received a diagnosis of neurasthenia, a condition ascribed to the effect of the stresses of modern life on the human nervous system the popu-larity of this diagnosis waned and by the mid-twentieth century it was rarely diagnosed (although the diagnosis subsequently became popular in the Far East—see Chapter 5.2.1). Although it is possible that the prevalence of chronic fatigue had waned in the population, it is more likely that patients who presented in this way were being given alternative diagnoses. These were mainly the new psychiatric syndromes of depression and anxiety, but also other labels indicating more direct physical explanations, such as chronic

brucellosis, spontaneous hypoglycaemia, and latterly chronic 
Epstein–Barr virus infection.
(2)
As well as these sporadic cases of fatiguing illness, epidemics of 
similar illnesses have been occasionally reported. One which 5.2.7 chronic fatigue syndrome

SECTION 5  psychiatry and medicine 1036
occurred among staff at the Royal Free Hospital, London in 1955 
gave rise to the term myalgic encephalomyelitis (ME), although it should be emphasized that the nature and symptoms of that outbreak are dissimilar to the majority of those now presenting to general practitioners under the same label.
A group of virologists and immunologists proposed the term 
chronic fatigue syndrome in the late 1980s.
(3) This new and aetio-
logically neutral term was chosen because it was increasingly recognized that many cases of fatigue were often not readily explained either by medical conditions such as Epstein–Barr virus infection or by obvious depression and anxiety disorders. Chronic fatigue syndrome has remained the most commonly used term by researchers. The issue of the name is still not completely resolved however: Neurasthenia remains in the ICD-10 psychiatric classiﬁ  -

cation as a fatigue syndrome unexplained by depressive or anxiety disorder, whilst the equivalent in DSM-IV is undifferentiated somatoform disorder. Myalgic encephalomyelitis or (encephalopa-thy) is in the neurological section of ICD-10 and is used by some to imply that the illness is neurological as opposed to a psychiatric one. Unfortunately the case descriptions under these different labels make it clear that they all reﬂ  ect similar symptomatic presen-
tations, adding to confusion. Ofﬁ  cial UK documents have increas-
ingly adopted the uneasy and probably ultimately unsatisfactory compromise term CFS/ME.
(4) In this chapter, we will use the 
simple term chronic fatigue syndrome (CFS).
Symptoms

Symptoms
Chronic mental and physical fatigue, tiredness, or exhaustion that is typically exacerbated by activity is the core symptom of CFS. Commonly associated symptoms include impaired memory and concentration, muscular and joint pain, unrefreshing sleep, dizzi-ness and breathlessness, headache, tender lymph glands, and sore throat. Patients often describe day-to-day ﬂ  uctuations in symp-
toms, irrespective of activity. Periods of almost complete recovery may be followed by relapse, often described as sufﬁ  ciently severe to 
make normal daily activity impossible. Depression and anxiety are common, and a proportion of patients suffer panic attacks.
Physical examination is typically unremarkable. Complaints of fever and lymphadenopathy are not conﬁ  rmed on examination.

Physical examination is typically unremarkable. Complaints of fever and lymphadenopathy are not conﬁ  rmed on examination. 
The presence of deﬁ  nite physical signs (such as objectively mea-
sured fever) should not be ascribed to the syndrome and alterna-tive diagnoses should be sought.
Other common characteristics
As well as the symptoms described above patients with CFS com-monly have additional clinical characteristics. These are listed in Table 5.2.7.1.
Patients are often worried that remaining active despite fatigue 
will harm them and consequently avoid activity or oscillate between rest and bursts of activity, which produces fatigue, leading to a return to rest and so on.
Some patients feel strongly that their illness is ‘medical’ rather than 
‘psychiatric’ and are particularly concerned that a psychiatric diag-nosis implies that the illness is their fault, an indication of personal weakness or even an accusation of malingering. Perfectionist and

high achieving lifestyles often with low underlying self-esteem are commonly observed in patients referred to hospital clinics.
Although there are no physical signs there may be measurable 
effects of reduced activity with so-called physiological decondition-ing leading to poor tolerance of activity, and in cases where rest has been prolonged other physiological changes such as postural hypo-tension. Sleep is often unrefreshing and fragmented.
Some patients can become markedly dependent on a carer. 
Occupational stresses and difﬁ  culties are common and it can be 
difﬁ cult to determine if these were contributors to, or are consequence 
of their illness. Finally many patients have received unhelpful medical attention. Such psychological iatrogenesis includes, on the one hand dismissal of their complaints and on the other over investigation.
(5)
Case study

(5)
Case study
A typical patient is found in the infectious disease department of the general hospital. She is a 30-years-old nurse and her principal complaints are of fatigue, poor concentration, and muscle pain. Her symptoms ﬂ  uctuate and are made worse by physical and men-
tal exertion. She is no longer able to work and has substantially reduced her daily activities. The history is of an acute onset of symptoms after a ‘viral illness’ . Enquiry reveals symptoms sugges-tive of depression or anxiety, but without obvious mood change. The patient strongly believes the illness to be ‘medical’ rather than ‘psychiatric’ .
There are several published case deﬁ  nitions for CFS. The currently 
most widely used deﬁ  nition is based on an international consensus 
of researchers is shown in Table 5.2.7.2.(6) A guide on its applica-
tion has also been published.(7) It should be remembered that this 
deﬁ nition represents nothing more than a working deﬁ  nition of

deﬁ nition represents nothing more than a working deﬁ  nition of 
a clinical problem, pending further understanding, and as with most psychiatric diagnoses, does not delineate a single disease.
Issues for a deﬁ  nition of chronic fatigue syndrome
The case deﬁ  nition shown in Table 5.2.7.2 has been useful in unify-
ing the ﬁ  eld and providing a widely used operational deﬁ  nition. 
However, it also has signiﬁ  cant limitations.Table 5.2.7.1  Common characteristics of patients with CFS
Thoughts beliefs and attitudes Thought that symptoms indicate harm
Belief that the illness is purely ‘medical’
Perfectionist attitudes
Coping behaviours Avoidance of activities associated with 
symptoms
Reduced activity levelOscillation in overall activity level
Physiology Poor sleep
Physiological deconditioning
Effects of inactivity
Interpersonal and socialDependence on carer 
Psychological iatrogenesis
Occupational difﬁ  culties

1037
◆ It excludes fatigue associated with known organic disease.
◆ It overlaps with other functional medical diagnoses.
◆ It overlaps with psychiatric diagnosis.
◆ The homogeneity of the patient group it identiﬁ  es is doubtful.
(a)  Differentiation from fatigue associated with 
organic disease
Fatigue is a common symptom of most medical and psychiatric 
conditions. CFS refers only to fatigue where there is no clear alter-native diagnosis (but does not exclude depression and anxiety unless the depression is of melancholic type or a manifestation of a bipolar disorder). It therefore only refers to idiopathic fatigue. This means that the deﬁ  nition highlights an important clinical problem 
but also means that the interesting equally important and probably informative phenomenon of fatigue in patients with diseases such as multiple sclerosis is excluded from this deﬁ  nition.
(b) Overlap with other medically unexplained syndromes

A number of medical diagnoses are deﬁ  ned only by symptoms. 
These functional syndromes are medical diagnoses where there is no identiﬁ  able pathology. They include chronic pain, ﬁ  bromyalgia, 
and irritable bowel syndrome. Although chronic pain syndromes 
are principally characterized by pain, fibromyalgia by tender points, and irritable bowel syndrome by symptoms of bowel dis-turbance, all these syndromes are also associated with chronic fatigue, and patients diagnosed with one of these syndromes often meet the diagnostic criteria for CFS.
(8)
(c) Overlap with psychiatric syndromes
Most patients who meet criteria for CFS also fulﬁ  l criteria for a 
psychiatric diagnosis. Many meet criteria for anxiety and depres-sive disorders and others merit diagnoses of somatoform disorder or neurasthenia. This issue is discussed further below.
(i) Depression
If patients with a depressive disorder are asked about a wide range

If patients with a depressive disorder are asked about a wide range 
of somatic symptoms including fatigue and/or muscle pain (which they are usually not) they often report these. If the diagnostic criteria for depressive disorders are applied to patients with fatigue 
a high proportion meet these.
(9) Furthermore the prevalence of 
major depressive disorder in patients referred to hospital with CFS is substantially higher than in patients with chronic disabling medical diseases suggesting that depression is not simply a reaction to disability.
(10) In practice, the diagnosis of depression can be 
difﬁ cult in patients presenting with fatigue: depressed mood is

difﬁ cult in patients presenting with fatigue: depressed mood is 
often not prominent and anhedonia can be hard to distinguish from the inability to pursue previously enjoyed activities because of fatigue. Finally, whilst there is a strong association between major depressive disorder and CFS, for as many as half of the patients seen in hospital clinics the symptoms cannot be readily given that diagnosis.
(ii) Anxiety disorders
Although less attention has been given to the association between 
fatigue and anxiety, an examination of diagnostic criteria for anxiety disorders reveals that the typical somatic symptoms of anxiety include fatigue and other symptoms listed as typical of CFS. If sought, generalized anxiety disorder can often be diagnosed in patients with CFS and panic can often be diagnosed in patients with severe episodic symptoms.
(11) As with depression, however,

(11) As with depression, however, 
anxious mood is rarely obvious and may be hard to distinguish from reasonable concern about consequences of being ill. Likewise, true phobic avoidance may be hard to distinguish from the conse-quences of fatigue and/or weakness.
(iii) Neurasthenia
ICD-10 differs from DSM-IV in including this diagnosis. It 
requires that the patient suffers from fatigue which is exacerbated by exertion, as well as several other somatic symptoms, and does not meet the criteria for a depressive or anxiety disorder (see Chapter 5.2.10). One study found that almost all of the referrals to a medical CFS clinic met the criteria for neurasthenia as deﬁ  ned 
by ICD-10.
(12)
According to DSM-IV patients with severe persistent fatigue who

by ICD-10.
(12)
According to DSM-IV patients with severe persistent fatigue who 
do not meet criteria for anxiety or depressive disorders are assigned to a somatoform disorder diagnosis. These are a controversial group of psychiatric syndromes characterized by medically unex-plained symptoms and of presumed psychological origin.
(13) There 
are a number of subcategories:
◆ Somatization disorder (Briquet’s syndrome) is used to describe 
patients who report multiple, recurrent, medically unexplained symptoms; a minority of patients with CFS will meet the criteria for this disorder.
◆ Hypochondriasis describes a syndrome in which the patient’s 
main concern is with the possibility that they are suffering from an organic disease. Whilst this diagnosis would seem to be appli-cable to many patients with CFS, it is problematic when the cause of the illness in question, which is regarded as uncertain by doctors as well as patients.

◆ Almost all patients with CFS not meeting the criteria for any of 
the above DSM disorders are likely to fall into the undemanding residual category in DSM-IV of ‘undifferentiated somatoform disorder’ . This diagnosis is of dubious practical use, and in effect merely conﬁ  rms that the patient has multiple physical symptoms 
of unclear aetiology.Table 5.2.7.2  International consensus deﬁ  nition of chronic fatigue 
syndrome
1 Complaint of fatigue
 Of new onset Not relieved by rest Duration at least 6 months2 At least four of the following additional symptoms Subjective memory impairment Sore throat Tender lymph nodes Muscle pain and joint pain
 Headache
 Unrefreshing sleep Post-exertional malaise lasting more than 24 h3 Impairment of functioning4 Other conditions that might explain fatigue excluded
(Reproduced from Fukuda, K. Straus, S.E. Hickie, I.B. et al.  Chronic fatigue syndrome: a 
comprehensive approach to its deﬁ  nition and management, Annals of Internal Medicine ,

comprehensive approach to its deﬁ  nition and management, Annals of Internal Medicine , 
121, 953–9. Copyright 1994, The American College of Physicians.)5.2.7 chronic fatigue syndrome

SECTION 5  psychiatry and medicine 1038
(v) Conclusion
Many patients with CFS meet the diagnostic criteria for a depres-
sive or anxiety disorder, although in practice the presentation is often ‘atypical’ . It is likely that patients who do not meet the criteria for either of these could be diagnosed as having either neurasthenia (ICD-10) or undifferentiated somatoform disorder (DSM-IV).
Should we use the diagnosis of CFS?
From the psychiatrist’s perspective it is parsimonious to ask whether a diagnosis of CFS is ever necessary or appropriate when the symptoms can always be described by a psychiatric diagnosis? This unsatisfactory situation is an artefact of parallel medical and psychiatric diagnostic systems for patients with somatic symptoms unexplained by disease. Consequently whether one uses a ‘medical’ diagnosis of CFS or a ‘psychiatric’ diagnosis of somatoform disor-der is merely a matter of choice. When making that choice the following must be considered:

◆ A diagnosis of CFS only describes a presenting clinical syndrome, 
rather than a speciﬁ  c disorder or disease process.
◆ Pragmatically the relative acceptability of the alternative 
diagnosis to the patient is important. There is no point in giving a diagnosis that is rejected by the patient and impedes any thera-peutic relationship and chances of treatment.
◆ One approach to overcoming the issue of parallel classiﬁ  cation 
systems is to combine the medical diagnosis of CFS and the psychiatric diagnoses: According to such a scheme CFS would be subclassiﬁ  ed into CFS/depression, CFS/anxiety, and CFS without 
depression or anxiety disorder (i.e. CFS/somatoform or CFS/neurasthenia). Psychiatric diagnoses that have important clinical utility such as major depressive disorder should obviously be made if present. The usefulness of diagnoses such as undifferen-tiated somatoform disorder is less clear.
◆ Finally rather than becoming side-tracked by the unanswerable

◆ Finally rather than becoming side-tracked by the unanswerable 
question of whether the patients symptoms are ultimately ‘medi-cal’ or ‘psychiatric’ in nature an open-minded and pragmatic approach is required.
Fatigue is common but CFS is rare. As it can be difﬁ  cult to differ-
entiate CFS from depressive and anxiety disorders estimates that have attempted to exclude these diagnoses are lower than those that have not. Population studies in the United Kingdom and United States suggest that only approximately 0.5 per cent of the population can be regarded as having CFS.
(1) Most of these per-
sons are aged between 20 and 40 with a predominance of females. The syndrome is also seen in children and adolescents but less commonly.
Epidemics

Epidemics
Epidemics of a chronic fatigue-like syndrome have been described from various parts of the globe. This observation is compatible with, but does not establish, an infective cause. It remains unclear whether these were true epidemics and also whether the clinical picture reported is similar to that of cases of sporadic chronic fatigue syndrome.Aetiology
Limitations in the available data
Although a considerable amount of research has been devoted to investigating the nature and causes of CFS there are few ﬁ  rm 
conclusions that can be drawn. This partly because many of the studies have had major methodological shortcomings:
◆ Patients have often been recruited from tertiary care clinics, 
using various diagnostic criteria inconsistently applied.
◆ Only a minority of studies have included comparison groups of

◆ Only a minority of studies have included comparison groups of 
patients with diagnoses of depression or anxiety disorders.
◆ Because most studies have used a case–control design, it is often 
impossible to know whether the ﬁ  ndings they report are causes 
or consequences of the illness (for instance, as the result of reduced activity or sleep disturbance).
◆ CFS is almost certainly heterogeneous.
Considering these caveats there are a number of areas where 
positive ﬁ  ndings have been reported.
Clinical observations of patients with CFS have led to the investi-
gation of a number of hypotheses about the underlying pathophys-iological mechanisms.
Twin studies suggest that CFS is moderately heritable.(1) Preliminary 
studies suggesting the involvement of speciﬁ  c genes require repli-

cation. Gene expression studies are likewise in their infancy—one problem being that the number of genes studied usually exceeds by several orders of magnitude the numbers of patients studied. Another problem is confounders—a large Swedish twin registry study for example suggested that genetic factors contributed to the risk of CFS both directly and via personality type.
(14)
(b) Cardiovascular and respiratory abnormalities
Several investigators have reported abnormalities in the cardio-respiratory systems that may underpin the exercise intolerance. Hyperventilation has been suggested as a mechanism of symptom production, but only a minority of patients have biochemically conﬁ  rmed hyperventilation. Low blood pressure has long been

associated with the symptom of fatigue, and in some parts of Europe unexplained fatigue is conﬁ  dently ascribed to this. Postural 
hypotension has been noted in some patients and whilst this may be a cause of fatigue it may also be a consequence of inactivity. Finally, various abnormalities in cardiac function have also been reported but are of uncertain signiﬁ  cance.
(c) Infection
Perhaps because patients commonly describe their illness as begin-
ning with ‘ﬂ  u-like symptoms’ and because of the apparent epidem ics, 
many investigators have sought objective evidence of an initiating or ongoing viral infection. Viral infection can probably initiate CFS. A prospective follow-up of people with positive evidence of acute Epstein–Barr infection did ﬁ  nd that some patients went on to 
develop a fatigue syndrome.
(15) Other infectious agents that may

(15) Other infectious agents that may 
trigger CFS include Q fever and viral meningitis. If viruses do play a role in precipitating CFS, it would appear that it is only when certain types of viruses infect vulnerable persons. If CFS can be

1039
precipitated by viral infection does persistence of the virus cause 
the ongoing symptoms? On current evidence the answer to this question seems to be no.
(d) Immune dysfunction
The evidence for an association between immunological abnor-malities and CFS is more consistent than that for infective agents, with several studies suggesting abnormalities in lymphocyte num-bers and function. However, similar changes can be found in patients with depressive disorders, and, although some studies have attempted to control for emotional disorder, both the speciﬁ  city 
and causal importance of these observations remain unclear.
(16)
(e) Sleep
Unrefreshing sleep is an almost ubiquitous complaint of people suffering from CFS. While studies have identiﬁ  ed major sleep dis-

(16)
(e) Sleep
orders such as sleep apnoea and narcolepsy as alternative diagnoses for small number of patients with daytime fatigue, simple disrup-tion of slow-wave sleep is a much more common observation. While inefﬁ  cient sleep could contribute to the daytime fatigue 
reported in both conditions, its speciﬁ  city and aetiological role 
are uncertain.
(16)
(f) Neuroendocrine and neurotransmitter abnormalities
The prominent fatigue of Addison’s disease has led to the hypothesis that adrenal function is impaired in patients with CFS. In support of this suggestion there is reasonable evidence that patients with chronic fatigue and ﬁ  bromyalgia have both low levels of cortisol, a

point of difference from major depression. However it remains unclear if this apparent abnormality is cause or effect of the illness and associated inactivity. Patients with CFS also have evidence of abnormal functioning of cerebral serotonergic systems, which differ from those found in patients with depression. Like the abnormalities in adrenal function these ﬁ  ndings are preliminary 
but of potential interest.
(17)
(g) Brain imaging
Finally, a variety of techniques have been used to examine both the function and structure of the brain in patients with CFS. Cerebral perfusion studies have shown abnormalities, although similar, if not identical, abnormalities are also found in patients with depres-sion. Possible white-matter changes reported on magnetic reso-nance scans are more controversial, and harder to interpret.
(1,16)
(h) Conclusions
Despite a considerable research effort, so far no single pathophys-iological process has been conclusively identiﬁ  ed as causal of CFS.

(1,16)
Despite a considerable research effort, so far no single pathophys-iological process has been conclusively identiﬁ  ed as causal of CFS. 
There is some evidence for a loss of physical ﬁ  tness and possibly 
for abnormalities of neuroendocrine function. Viral infection can play a role as precipitating agent, although its importance as a perpetuating factor is less certain. Immunological abnormalities are common but of uncertain speciﬁ  city, and appear not to be 
related to chronic symptoms. The current attention on neuroen-docrine function takes the focus of investigation closer to those features known to be associated with depressive states. However, the evidence suggests that the changes in neurotransmitter and neuroendocrine function in patients with CFS may differ from those commonly observed in patients diagnosed with depressive disorder. Further studies are needed to conﬁ  rm all

these abnormalities and to clarify whether they are causal or merely epiphenomena.Psychopathology
If there are no substantial biological abnormalities are there psychological ones? The initial psychiatric explanation of CFS was that it was misdiagnosed depressive disorder. However, whilst such misdiagnosis does occur, more complex explanations are required to adequately explain many cases of CFS.
(a) Somatization
It has been hypothesized that depression may still be ‘behind’ CFS even if not apparent. It is argued that a process referred to as ‘soma-tization’ (making the mental physical) is responsible. Whist the idea that the somatic symptoms of CFS are readily understandable as part of an emotional disturbance is a parsimonious alternative to some of the more elaborate mechanisms outlined above, as there is no ‘marker’ for somatization this hypothesis is hard to prove.
(b) Attribution

Patients attending specialist clinics with CFS typically attribute their illness to organic disease even when no evidence of this can be found by their physicians. Perhaps more importantly, some strongly resist psychological explanations for their illness, although most take a more mixed view. Whether these patients are biased in their views about illness or simply wiser than their physicians is unclear. However, strong and exclusively physical disease attributions may be a marker for an important illness-perpetuating process in CFS as they predict a poorer clinical outcome.
(c) Perceptual processes

Patients with CFS report a greater sense of effort in response to both psychological and physical demands than is explicable from objectively measured impairments. This observation raises the pos-sibility that they are especially sensitive to bodily sensations such as effort, that is they ‘amplify’ or focus on them. Thus, one may hypothesize that as in panic disorder, the patients’ beliefs about their symptoms may lead them to focus attention on to bodily sensations. Although plausible there is so far only limited evidence that this process is important in patients with CFS.
(1)
(d) Coping behaviour

(1)
A tendency to avoid activities that exacerbate symptoms has been shown to occur in patients with CFS. The avoidance may be persis-tent or episodic in response to exacerbations of symptoms resulting in a ‘boom and bust’ pattern. Avoidance is associated with persistent disability, and has been suggested as the mechanism by which disease attributions for symptoms predicts poor outcome.
(1)
(e) Personality characteristics
Both research studies and clinical experience suggest that many per-sons with CFS have a tendency towards hard driving, perfectionist, or obsessive–compulsive personalities, and associated overactive lifestyles. Evidence from the UK 1946 birth cohort for example indi-
cates that ratings of physical activity in early life predict later CFS. 
In a large prospective Swedish twin registry measure of stress and 
emotionality are consistently associated with subsequent CFS. Those 
CFS sufferers may be predisposed to becoming physically and

CFS sufferers may be predisposed to becoming physically and 
emotionally exhausted, and biased towards presenting emotional distress in a somatic form.
(14)
(f) Stigma, misinformation, and iatrogenesis
Psychiatric diagnoses are stigmatized in the popular mind as indi-cating weakness or even unreal illness. Patients with CFS may be 5.2.7 chronic fatigue syndrome

SECTION 5  psychiatry and medicine 1040
susceptible to those social pressures and consequently prefer a 
medical diagnosis for their distress and inability to function. It has also been suggested that CFS may serve as culturally deﬁ  ned func-
tion of social communication, allowing a socially acceptable and hence ‘non-psychiatric’ expression of distress and protest about intolerable occupational and personal pressures. Much the same was said of neurasthenia in the People’s Republic of China (see Chapter 5.2.1).
Another potentially important social factor is the controversy 
and the often misleading information about the illness that patients are exposed to. Self-help books the media and some doctors have frequently given the impression that the medial profession is more divided than it actually is in its understanding of CFS and have emphasized ‘medical’ explanations such as myalgic encephalopathy (ME) as the only appropriate diagnosis.
(g) Conclusions

Psychological and social factors are important perpetuating factors and include focusing of attention on symptoms avoidance of activity and a strong and exclusive medical disease attribution.
A comprehensive view of the cause of CFS
It now seems clear that rather than regarding pathophysiological and psychopathological studies as separate and competing approaches to the problem, it is more useful to consider a formula-tion of CFS that combines these factors. Table 5.2.7.3 summarizes relevant aetiological factors.
According to this integrated scheme causal factors are divided

According to this integrated scheme causal factors are divided 
into those that may predispose to the illness, those that precipitate it, and those that perpetuate an established illness. Predisposing factors include previous episodes of major depressive disorder, and perhaps also certain personality characteristics, particularly achievement orientation and perfectionism associated with chronic stress, especially occupational stress. The precipitation of CFS by a viral infection is clinically plausible and proven in certain cir-cumstances, whilst life stresses also seem to be important. 
Perpetuating factors may include neuroendocrine dysfunction, emotional disorder, and physical disease attributions, as well as 
coping by avoidance, chronic unresolved personal difﬁ  culties, and 
misinformation about the illness. They may be effectively com-bined in a cognitive–behavioural model of the illness that provides a basis for treatment with CBT.
(1,18)
Course and prognosis of CFS

(1,18)
Anecdotal reports of the prognosis of CFS make gloomy reading. What is more, systematic studies are hardly more encouraging, suggesting that the commonest outcome of those attending a spe-cialist CFS clinic is continuing ill health, up to and beyond 5 years.
(19)
However, these observations need elaboration. The rather dispirit-ing prognostic studies all refer to patients seen in specialist centres. Nearly all had several years of illness prior to referral, and it is unsurprising to ﬁ  nd that chronicity predicts chronicity. Patients 
seen in specialist clinics often have strong views about illness  aetiology and illness management that may negatively inﬂ  uence

seen in specialist clinics often have strong views about illness  aetiology and illness management that may negatively inﬂ  uence 
their acceptance of and adherence to potentially effective treat-ment. Primary care and community samples and patients appear to have a better outcome, as do children and adolescents. Finally, the current generation of outcome studies refer to the situation without treatment as potentially effective treatment was rarely 
given. Later sections of this chapter suggest that this view requires  revision.
Evidence for treatments
Many pharmacological treatments have been suggested for CFS. T o date, none are of proven efﬁ  cacy and several are potentially harm-
ful.
(4, 20) The evidence for antidepressant agents is mixed. Of avail-
able agents none is clearly superior for this patient group, although clinical experience suggests that the selective serotonin-reuptake inhibitor antidepressants may be better tolerated.

Graded activity (exercise) therapy
Well-conducted randomized controlled trials suggest that graded increases in physical activity is helpful in improving function and relieving symptoms.
(4, 20)
Cognitive behaviour therapy
Systematic reviews have concluded that the strongest evidence for efﬁ cacy is for a rehabilitative type of cognitive–behaviour therapy 
(CBT).
(4, 20)
Practical management
Both a medical and psychiatric assessment is required in every case of suspected CFS.
(21)
(a) Excluding organic disease

(CBT).
(4, 20)
(21)
A small minority of those patients who present with severe chronic fatigue will be found to have occult organic disease. How frequently organic disease is found will depend on how thorough an assess-ment the patient has already received. The differential diagnosis is listed in Table 5.2.7.4.
There are no speciﬁ  c diagnostic tests and no characteristic 
abnormalities on laboratory investigations in CFS. T ests are con-ducted purely to exclude other diseases. All patients should have a full blood count, erythrocyte sedimentation rate or C-reactive Table 5.2.7 .3 An aetiological formulation of CFS
Predisposing Precipitating Perpetuating
Biological Genetics Infection Effects of 
inactivity
Previous depression CNS dysfunction
Reduced HPA 
activity
Psychological Personality 
(perfectionism)Response to 
stressorFocus on

activity
stressorFocus on 
symptoms
Disease 
attribution
Avoidant coping
Social Chronic stress Social/occupation 
stressLife conﬂ  icts
Psychological 
iatrogenesis

1041
protein, basic biochemistry screen, creatine kinase, random
blood glucose, urine analysis, thyroid function, and possibly anti-nuclear antibody tests. Further investigation depends on the  clinical ﬁ  ndings and differential diagnoses under consideration. 
In our clinical experience unusual clinical features, such as weight loss, an absence of mental fatigue/fatigability, or a history of recent foreign travel, should all increases suspicion of alterna-tive diagnoses.
(b) Excluding psychiatric diagnoses
All patients should have a psychiatric history taken and their mental state examined. The assessment should seek evidence of major depression, anxiety, and panic disorder, and also evaluate any suicidal intent. The psychiatric assessment should be systematic, as hidden distress is common and casual estimates of the patient’s degree of distress may be misleading.
Making the diagnosis
As explained above the choice of diagnosis should be pragmatic;

As explained above the choice of diagnosis should be pragmatic; 
there is little merit in giving a diagnosis of CFS if the patient’s 
symptoms are clearly those of depression or anxiety. In other cases, 
a diagnosis of CFS may be the most appropriate and useful; it offers 
the patient a coherent label for their symptoms and will therefore lessen the risk that they will embark on a fruitless search for a ‘better’ explanation. Above all, it is most important that neither the physician nor the patient stops at this diagnosis, but goes on to explain what it does and does not mean.Making a formulation
An adequate individual patient assessment must identify all the important obstacles to recovery. It often needs to go beyond diag-nosis to include a systematic individualized description of the aetiological factors in each case. These should include those factors listed in Table 5.2.7.1.
(a) Case formulation

A multidimensional description of the patient’s illness provides a comprehensive picture of the factors that may be relevant to the patient’s illness and is an important supplement to diagnosis. Its use can be illustrated by returning to the case example described above.
Case Study
Assessment of the patient described earlier revealed that she

Case Study
Assessment of the patient described earlier revealed that she 
believed that her symptoms were by an ongoing virus infection and associated immune disturbance and that she should beware of exacerbating them. She consequently avoided activity and had been profoundly inactive for over a year, often lying in bed and sleeping for long periods. Therefore she had become physiologically decon-ditioned. She was frustrated with her inability to do things and sometimes felt low in mood about her predicament. Her previous job had been very stressful, but since becoming ill she had been unable to work. She had now lost her job and was cared for by her mother who also believed she had a permanent disability. Her doctor said that the best thing was rest. She had rejected a psychiat-ric consultation but was paying to see an alternative medicine therapist.
The ﬁ  ndings can be summarized in an individualized form of

The ﬁ  ndings can be summarized in an individualized form of 
Table 5.2.7.3 with an emphasis on the perpetuating factors, which can be seen as reversible barriers to recovery.
General management
The ﬁ  ve basic steps essenstial to the care of patients with CFS are 
listed in Table 5.2.7.5.
The doctor should listen to the patient’s story and ask about his

The doctor should listen to the patient’s story and ask about his 
or her own understanding of the illness. It is usually also worth see-ing the partner or relevant family members. It is important to address misunderstandings about the nature of the illness and especially to make clear that it is not progressive or life threatening. A positive explanation of CFS as a ‘dysfunction of the central ner-vous system’ emphasizing reversibility is often helpful. Anxiety and depression can be explained as understandable consequences of illness and treatment given for them. The adverse physiological and psychological effects of prolonged bed rest should be explained, and the patient encouraged to avoid extremes of both inactivity Table 5.2.7.4  Conditions to be considered in the differential 
diagnosis of chronic fatigue syndrome
Nature of symptoms Possible condition

General Occult malignancy
Autoimmune disease
Cardiac, respiratory, or renal failure
Gastroenterological Malabsorption including celiac disease
Neurological Disseminated sclerosis
Myasthenia gravis
Early dementiaCerebrovascular disease
Infectious disease Chronic active hepatitis (B or C)
Lyme borreliosisHIVTuberculosis
Respiratory disease Nocturnal asthma
Obstructive sleep apnoea
Chronic toxicity Alcohol
Solvents
Heavy metals
Irradiation
Psychiatric Major depressive disorder
DysthymiaAnxiety and panic disorderSomatoform disorder
Table 5.2.7.5  Principles of management of CFS
1 Acknowledge the reality of the patient’s symptoms and disability
2 Provide appropriate education about the nature of the syndrome3 Treat identiﬁ  able depression and anxiety disorder4 Encourage a very gradual return to normal functioning

5  Help the patient overcome occupational and interpersonal obstacles to 
normal functioning5.2.7 chronic fatigue syndrome

SECTION 5  psychiatry and medicine 1042
and exertion. Finally there are often problem in relationships and 
with employers than the patient may need help to address.
An initial hospital appointment that achieves all the above 
usually requires at least 45 min. An evidence-based self-help book may be recommended.
(22)
(a) Pharmacological treatments
Patients are often reluctant to take antidepressants and careful explanation and follow-up are required. Other pharmacological agents should only be used with care and preferably only as part of randomized controlled trials.
(b) Graded activity and exercise therapy
This should be considered for patients who are physically inactive. However, they need to be slowly graded and tailored to the patients’ 
ability and progress; a simplistic application of ﬁ  xed exercise 
regimens, particularly if given without adequate explanation is unlikely to be helpful, and may exacerbate symptoms and damage conﬁ  dence.
(c) CBT

(c) CBT
Whilst CBT is currently the mainstay of management it is not effec-
tive in all patients and requires both careful explanation and thera-pists skilled in its delivery to patients with CFS. It is particularly important that patients do not interpret referral for a behavioural treatment as the doctor implying that their illness is imaginary. It can be explained that the most likely cause of fatigue in CFS is changes in brain and neuroendocrine function and that these can be reversed by these therapies. It is also both useful and true to draw attention to studies showing the effective of CBT in improv-ing symptoms, quality of life and outcome in conditions such as diabetes, cancer, and rheumatoid arthritis. General physical reha-bilitation services may be useful for patients with chronic severe disability.
Potential management problems

Several issues may complicate the management of patients with CFS. These include:
(a) Strong illness beliefs
Difﬁ culties are most likely to arise when patient and physician hold 
differing beliefs about the nature and best management of the ill-ness. This problem can often be overcome by the physician acknowledging the patient’s beliefs without either agreeing with them or arguing about them. If the patient’s family, friends, or acquaintances suggest or encourage views that the physician regards as unhelpful the problem is more difﬁ  cult and a meeting with the 
other parties may be necessary.
(b) Alternative therapies

Patients with CFS often turn to alternative and complementary medicine. Whilst some of these therapies may be easily continued in parallel with rehabilitative management, others may interfere either by the explanation of the illness they offer or by their practi-cal requirements. In such cases it can be helpful to explain the need to pursue one approach at a time in order to learn what helps.
(c) Ofﬁ  cial reports and ﬁ  nancial beneﬁ  ts
Perhaps the greatest difﬁ  culty is when patients ask the physician 
to write reports on their behalf, conﬁ  rming that they suffer from 
permanent disability. The physician wants to help the patient and ensure that they get appropriate beneﬁ  ts but also to avoid a self-
fulﬁ lling prophecy. This dilemma has no easy solution, but it seems 
important not to conﬁ  rm a negative prognosis until potentially 
effective treatment has been tried.
(d) Poor prognosis patients

For patients who have been identiﬁ  ed as having a poor prognosis 
because of a long history of severely impaired functioning, or poor response to treatment, regular (albeit infrequent) long-term follow-up is, at the least, likely to limit iatrogenic harm from unnec-essary investigations and ineffective treatments. Often in such cases the best strategy is simply to tell the patient how well they are managing in difﬁ  cult circumstances.
We do not know how to prevent CFS, but its development can 
probably be modiﬁ  ed. 
The most important place for such intervention may be the tran-

sition from an acute fatigue state to chronic disability. For example, although most of us have been exposed to Epstein–Barr virus infec-tion by the time we reach 30 years of age, few go on to develop CFS. Encouraging modest amounts of activity in the weeks after an acute infection has been shown to be effective in reducing the duration of symptoms. Intervention that maintain activity and prevent a slide into a vicious circle of symptoms, reduced activity, demoral-ization, disability, and depression might therefore offer an opportunity for prevention. The second area for intervention is in achieving better attitudes to symptoms and distress. Simplistic depictions of illness as either physical or psychological and the corresponding division in medical services are clearly unhelpful. The third area is in employment practice. CFS is often associated with work stress and dissatisfaction and only a minority of employers allow a ﬂ  exible return to work. Finally, a doctor–patient relation-

ship that both allows the patient to be ill and encourages recovery is probably the most important preventive strategy.
Conclusions and future directions
Chronic fatigue syndrome is best regarded as a descriptive term for a clinical presentation, rather than as a discrete condition. The group of patients it deﬁ  nes is almost certainly aetiologically 
heterogeneous. While psychiatric diagnosis provides one approach to subclassiﬁ  cation of CFS, both the medical and psychiatric 
current diagnostic systems have signiﬁ  cant limitations, and a 
multidimensional description of the patient’s characteristics may be more clinically useful.
(23)
The illness deﬁ  ned by the term chronic fatigue syndrome is

(23)
The illness deﬁ  ned by the term chronic fatigue syndrome is 
important because it represents potentially treatable disability and suffering. It is also important because the clinical problems it gives rise to highlight shortcomings in our present approach to illness. Whatever is ultimately discovered about the causes of CFS, the attention it is receiving offers a golden opportunity to reappraise our understanding and classiﬁ  cation of human illness and to 
re-examine our current organization of medical care.
Wessely, S., Sharpe, M., and Hotopf, M. (1998). Chronic fatigue and its 
syndromes . Oxford University Press, Oxford.

1043
National Institute for Health and Clinical Excellence Guideline 
number 53. Chronic fatigue syndrome/ myalgic encephalomyelitis 
(or encephalopathy); diagnosis and management. http://guidance.nice.org.uk/CG53
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fatigue syndrome. Lancet ,367, 346–55.
 2. Wessely, S., Hotopf, M.H., and Sharpe, M. (1998). Chronic fatigue and 
its syndromes . Oxford University Press, Oxford.
 3. Holmes, G.P ., Kaplan, J.E., Gantz, N.M., et al. (1988). Chronic fatigue 
syndrome: a working case deﬁ  nition. Annals of Internal Medicine ,
108, 387–9.
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fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. British Medical Journal ,335, 446–8.
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lessons from chronic fatigue syndrome. General Hospital Psychiatry ,
20, 335–8.

5. Sharpe, M. (1998). Doctors’ diagnoses and patients’ perceptions: 
20, 335–8.
 6. Fukuda, K., Straus, S.E., Hickie, I.B., et al. (1994). Chronic fatigue 
syndrome: a comprehensive approach to its deﬁ  nition and 
management. Annals of Internal Medicine ,121, 953–9.
 7. Reeves, W.C., Lloyd, A., Vernon, S.D., et al. (2003). Identiﬁ  cation 
of ambiguities in the 1994 chronic fatigue syndrome research case deﬁ nition and recommendations for resolution. BMC Health Services 
Research ,3, 25.
 8. Wessely, S., Nimnuan, C., and Sharpe, M. (1999). Functional somatic 
 9. Skapinakis, P ., Lewis, G., and Meltzer, H. (2000). Clarifying the 
relationship between unexplained chronic fatigue and psychiatric morbidity: results from a community survey in Great Britain. The American Journal of Psychiatry ,157, 1492–8.

10. Katon, W., Buchwald, D.S., Simon, G.E., et al. (1991). Psychiatric illness 
in patients with chronic fatigue and rheumatoid arthritis. Journal of 
General Internal Medicine ,6, 277–85.
11. Fischler, B., Cluydts, R., De Gucht, Y., et al. (1997). Generalized anxiety 
disorder in chronic fatigue syndrome. Acta Psychiatrica Scandinavica ,
95, 405–13.
12. Farmer, A., Jones, I., Hillier, J., et al. (1995). Neurasthenia revisited. 
British Journal of Psychiatry ,167, 496–502.
13. Mayou, R., Kirmayer, L.J., Simon, G., et al. (2005). Somatoform 
14. Kato, K., Sullivan, P .F., Evengard, B., et al. (2006). Premorbid predictors 
of chronic fatigue. Archives of General Psychiatry
,63, 1267–72.

15. White, P .D., Thomas, J.M., Amess, J., et al. (1995). The existence of 
a fatigue syndrome after glandular fever. Psychological Medicine ,25,
907–16.
16. Afari, N. and Buchwald, D. (2003). Chronic fatigue syndrome: a review. 
American Journal of Psychiatry ,160, 221–36.
17. Cho, H.J., Skowera, A., Cleare, A., et al. (2006). Chronic 
fatigue syndrome: an update focusing on phenomenology and pathophysiology. Current Opinion in Psychiatry ,19, 67–73.
18. Surawy, C., Hackmann, A., Hawton, K.E., et al. (1995). Chronic fatigue 
syndrome: a cognitive approach. Behaviour Research and Therapy ,
33, 535–44.
19. Cairns, R. and Hotopf, M. (2005). A systematic review describing 
the prognosis of chronic fatigue syndrome. Occupational Medicine
(London ), 55, 20–31.

20. Chambers, D., Bagnall, A.M., Hempel, S., et al. (2006). Interventions
for the treatment, management and rehabilitation of patients 
with chronic fatigue syndrome/myalgic encephalomyelitis: an 
updated systematic review. Journal of the Royal Society of Medicine ,
99, 506–20.21. Sharpe, M., Chalder, T., Palmer, I., et al. (1997). Chronic fatigue 
syndrome. A practical guide to assessment and management. General 
Hospital Psychiatry ,19, 185–99.
22. Campling, F. and Sharpe, M. (2000). Chronic fatigue syndrome: the facts .
23. Sharpe, M., Mayou, R., and Walker, J. (2006). Bodily symptoms: 
new approaches to classiﬁ  cation. Journal of Psychosomatic Research ,
60, 353–6.
5.2.8 Body dysmorphic disorder

60, 353–6.
The dysmorphophobic patient is really miserable; in the middle of his 
daily routines, talks, while reading, during meals, everywhere and at any time, he is caught by the doubt of deformity . . . . Enrico Morselli, 1891
(1)
Body dysmorphic disorder (BDD), also known as dysmorphopho-bia, is a relatively common, severe, and sometimes difﬁ  cult-to-treat 
condition that has been described for more than a century.
(1–3)
BDD consists of a distressing or impairing preoccupation with an imagined or slight defect in one’s physical appearance. BDD is clas-siﬁ ed as a separate disorder in DSM-IV and a type of hypochon-

driasis in ICD-10. This disorder can cause severe distress and notably impaired functioning. In addition, risk behaviours—suicidality, violence, problematic substance use, and compulsive tanning—appear common in BDD. Despite its severity, BDD is underrecog-nized in clinical settings.
Demographic characteristics
BDD occurs in all age groups.(3–5) It appears about equally common 
in females and males or may be somewhat more common in females.
(3) Most individuals with BDD have never been married, 
and a high proportion is unemployed, often because of their psychopathology.
(3–7)
Bodily preoccupations
People with BDD are preoccupied with the idea that some aspect of their appearance is ugly, unattractive, deformed, ﬂ  awed, or 
defective in some way.

(3–7)
(1–6, 8–10)  Concerns usually focus on the face 
or head but can involve any body area.(3–6, 8–10)  Skin (e.g. acne, 
scars, lines, or pale skin), hair (e.g. thinning or excessive body or facial hair), and nose (e.g. size or shape) concerns are most common. Most patients are preoccupied with several body areas. The preoccupation usually focuses on speciﬁ  c areas but may involve 
overall appearance.
BDD preoccupations are distressing, time consuming (occurring 
for an average of 3–8 h a day), and usually difﬁ  cult to resist or 
control.
(3) They are often associated with low self-esteem, shame, 
rejection sensitivity, and high levels of neuroticism, introversion, 5.2.8 body dysmorphic disorder

SECTION 5  psychiatry and medicine 1044
depressed mood, anxiety, anger-hostility, and perceived stress.(3)
Patients often believe that they are unacceptable—e.g. worthless, 
inadequate, unlovable, and an object of ridicule and rejection.(3,9)
Insight/delusionality
Insight is usually poor or absent; 27–39 per cent of patients are cur-rently delusional (completely convinced that their belief is accurate and undistorted).
(3, 11, 12) Most do not recognize that their belief is 
due to a mental illness or has a psychological/psychiatric cause.(3, 12)
In addition, a majority have ideas or delusions of reference, believ-ing that others take special notice of the supposed appearance defects—for example, stare at them or mock the person because of how they look.
(3, 12) Referential thinking can fuel feelings of anger 
and rejection as well as social isolation.
Compulsive and safety behaviours

Nearly all patients perform BDD-related compulsive or safety behaviours (Table 5.2.8.1), which are time consuming (occurring for hours a day) and difﬁ  cult to resist or control.
(3–6,10)  The behav-
iours usually aim to examine, improve, hide, or obtain reassurance about the perceived defects. These behaviours typically do not alleviate distress and may even worsen it.
Compulsive skin picking, which 27–45 per cent of BDD patients 
do to try and improve their appearance, can cause considerable skin damage.
(3,5) Emergency surgery is sometimes required—for 
example when sharp implements used for picking rupture major blood vessels. Compulsive tanning to darken ‘pale’ skin or mini-mize perceived acne, scarring, or ‘marks’ can cause skin damage and may increase cancer risk.
(3)
Psychosocial functioning and quality of life

(3)
Functioning and quality of life are usually very poor.(3, 4, 7)  Some 
people, with effort, function adequately despite their distress, although usually below their potential. Those with severe BDD may be profoundly impaired by their symptoms—for example, 
housebound for years, unemployed and socially isolated, and chronically suicidal.
Social impairment is nearly universal.
(3, 7) People with BDD feel 
embarrassed and ashamed of their ‘ugliness’ , are anxious around others as a result, and fear being rejected because of how they look. Thus, they may have few or no friends; avoid dating, physical inti-macy, and other social interactions; or get divorced. Impairment in academic or occupational functioning is common, due to the time consuming and distracting nature of BDD symptoms and a desire to avoid interactions with others.
(3, 7) In a broadly ascertained BDD 
sample ( n = 200), 36 per cent of individuals were not currently

sample ( n = 200), 36 per cent of individuals were not currently 
working and 32 per cent were not able to be in school or do school work because of psychopathology (BDD was the primary diagnosis for most).
(7) In two BDD series, more than a quarter of individuals 
had been completely housebound for at least 1 week because of BDD symptoms, and more than 40 per cent had been psychiatri-cally hospitalized.
(5,13)  Mental health related quality of life is 
markedly poorer than for the general population and even poorer than for patients with diabetes, a recent myocardial infarction, or clinical depression.
(7)
Suicidality
Suicidal ideation and attempts appear very common. Reported lifetime rates of suicidal ideation and suicide attempts are 78–81 and 24–28 per cent, respectively.
(9,13,14) Among adolescent 
inpatients, those with BDD have signiﬁ  cantly greater suicidality

inpatients, those with BDD have signiﬁ  cantly greater suicidality 
than those without BDD. The rate of completed suicide, while preliminary,  appears markedly high. In a prospective study, the annual suicide rate was 0.35 per cent, which is approximately 45 times higher than for the US population (adjusted for age, gender, and geographic region) and higher than for most other mental dis-orders.
(15) A study of dermatology patients who committed suicide 
found that most had acne or BDD.(16) Indeed, individuals with 
BDD have many suicide risk factors.(3,14)
Aggression and violence
In several BDD studies, 36–38 per cent of patients reported life-time aggression/violence due speciﬁ  cally to BDD symptoms.
(3,10)
Such behaviour may be fuelled by anger about looking ‘deformed’ , 
an inability to ﬁ  x the perceived defect, and misperceptions of being

(3,10)
an inability to ﬁ  x the perceived defect, and misperceptions of being 
rejected, ridiculed, or mocked because of the appearance ‘defects’ . Individuals with BDD tend to misinterpret self-referent facial expressions as contemptuous and angry,
(17) misinterpret ambigu-
ous social (and other) situations as threatening,(18) and have high 
levels of anger/hostility.(3) Surgeons and dermatologists may be 
victims of violence—even murder—fuelled by dissatisfaction with the outcome of cosmetic procedures.
(3) In a survey of 265 plastic 
surgeons, 12 per cent reported that a BDD patient had physically threatened them.
(19)
Major depressive disorder is the most frequently comorbid disorder, occurring in about 75 per cent of individuals with BDD.
(5, 13) Social 
phobia, OCD, and substance use disorders are also common.(5, 8, 13)

Of note, one study found that 49 per cent of 200 BDD subjects had a lifetime substance use disorder, 70 per cent of whom reported that BDD contributed to their substance use.
(5) Muscle dysmorphia, Table 5.2.8.1  Common compulsive and safety behaviors in body 
dysmorphic disorder
◆  Comparing one’s appearance ‘defects’ with the same body areas of other 
people
◆  Checking the perceived defects directly, in mirrors, or in other reﬂ  ecting 
surfaces
◆  Excessive grooming—for example, applying make-up, shaving, hair cutting 
or removal, hair styling
◆  Camouﬂ  aging—for example with a hat, clothes, sunglasses, hair, body 
position, hand, or make-up
◆  Seeking reassurance from others or trying to convince others of the ‘defect’s’ 
ugliness
◆ Skin picking
◆ Excessive exercising or weightlifting
◆ Tanning
◆  Frequent clothes changing
◆ Touching the perceived defect
◆ Dieting
◆ Body measuring

ugliness
◆ Tanning
◆ Dieting
◆ Compulsive shopping for beauty products, remedies, or clothes
◆  Seeking surgical, dermatologic, and other cosmetic treatment for the 
perceived deformity

1045
a preoccupation with the idea that one’s body is insufﬁ  ciently lean 
or muscular, may lead to anabolic steroid abuse.(3)
Gender
Men and women appear to have largely similar clinical features.
(10, 13, 20)  However, in two United States studies ( n = 200 
and n = 188(13, 20)) males were more likely to be single, have a sub-
stance use disorder, and be preoccupied with thinning hair and small body build. Females were more likely to be preoccupied with weight, hips, and excessive body hair, and were more likely to pick their skin and use their hands or make-up for camouﬂ  age. One of 
these two studies, and a study from Italy ( n = 58
(10)), found that 
females were more likely to be preoccupied with their breasts/chest and legs, check mirrors, and use camouﬂ  aging. In all three studies, 
a concern with genitals was more common in males, and a comor-bid eating disorder more common in females.
BDD in children and adolescents

BDD usually begins during early adolescence and can occur in childhood.
(4, 5, 10) While data are limited, BDD’s clinical features in 
youth appear largely similar to those in adults. Of note, children and adolescents appear to have lifetime rates of functional impairment similar to those in adults, despite having had fewer years over which to have developed these problems.
(3) In the one study that directly 
compared adolescents to adults, adolescents were more likely to have delusional BDD beliefs and had a signiﬁ  cantly higher lifetime 
suicide attempt rate (44 per cent versus 24 per cent), underscoring the importance of recognizing BDD in this age group.
Cross-cultural aspects of BDD

Case reports and series from around the world suggest that BDD’s clinical features are generally similar across cultures but that cul-tural factors may produce nuances and accents on a basically invariant, or universal, expression of BDD.
(3) It is unclear whether 
koro (a belief that one’s penis is shrinking, which occurs primarily in Southeast Asia) is a form of BDD.
Classiﬁ  cation and relationship to 
other disorders
A clinically important classiﬁ  cation controversy is whether delu-
sional and non-delusional BDD are the same or different disorders. Whereas BDD is classiﬁ  ed as a somatoform disorder, its delusional 
variant is classiﬁ  ed as a psychotic disorder—a type of delusional 
disorder. DSM-IV , however, allows delusional patients to be diagnosed with both BDD and delusional disorder, reﬂ  ecting data

disorder. DSM-IV , however, allows delusional patients to be diagnosed with both BDD and delusional disorder, reﬂ  ecting data 
suggesting that its delusional and non-delusional variants may constitute the same disorder, which spans a spectrum of insight. Indeed, delusional and non-delusional BDD appear more similar than different, although delusional BDD appears more severe.
(11,12)
Of clinical signiﬁ  cance, delusional and non-delusional patients 
both appear to respond to serotonin-reuptake inhibitors (SRIs) as monotherapy but not to antipsychotic monotherapy.
(21)
Another important question is whether BDD is related to OCD, 
social phobia, major depressive disorder, or eating disorders.(3)
BDD is widely conceptualized as an OCD-spectrum disorder. Supporting this conceptualization, OCD often co-occurs with BDD, and BDD appears more common in ﬁ  rst-degree relatives of OCD probands than control probands.

(3) Data from a variety of 
domains suggest that BDD and OCD have many similarities.(3)
However, BDD and OCD have some differences and do not appear to be identical disorders.
(3) Although BDD’s relationship to other 
disorders has received less investigation, preliminary data suggest that BDD may also be related to major depressive disorder. However, BDD does not appear to simply be a symptom of depres-sion.
(3) Although ICD-10 classiﬁ  es BDD as a type of hypochondri-
asis, no studies have examined their relationship.
Diagnosis
BDD can be diagnosed using questions at the top of Table 5.2.8.2, which follow DSM-IV’s diagnostic criteria. Clinicians should ade-quately probe for examples of clinically signiﬁ  cant distress and 
impairment in social, occupational, and other aspects of function-ing. BDD is diagnosed if the person is excessively preoccupied with a non-existent or slight physical ﬂ  aw (for example, thinks about it

for at least an hour a day), and the concern causes clinically signiﬁ  -
cant distress or impairment in functioning. The appearance con-cerns should not be better accounted for by an eating disorder. However, BDD and eating disorders may co-occur, in which case both disorders should be diagnosed.
The bottom of Table 5.2.8.2 includes questions that are not rec-
ommended for screening for or diagnosing BDD. The word ‘imag-
ined’ is problematic, because most patients have poor or absent 
insight and do not think their appearance problem is imagined. T erms such as ‘deformed’ or ‘disﬁ  gured’ are too extreme for some 
patients to endorse. Asking if there is something wrong with one’s body is too broad, as patients may interpret this to refer to bodily functioning.
ICD-10’s criteria require that patients persistently refuse to

ICD-10’s criteria require that patients persistently refuse to 
accept the advice and reassurance of several different doctors that they do not have an abnormality. However, many people with BDD do not disclose their appearance concerns to doctors or even seek medical care because they are housebound, ashamed, believe they cannot be helped, lack medical insurance, or do not have access to 
Table 5.2.8.2  Questions to diagnose BDD
Recommended questions for diagnosing BDD:
1  Are you very worried about your appearance in any way? OR: Are you 
unhappy with how you look? If yes:  Can you tell me more about your 
concern?
2  Does this concern preoccupy you? Do you think about it a lot and wish 
you could worry about it less? How much time would you estimate you 
spend each day thinking about how you look, if you were to add up all the 
time you spend?
3  What effect does this preoccupation with your appearance have on your

3  What effect does this preoccupation with your appearance have on your 
life? Has it caused you a lot of distress (for example, anxiety or depression)? Has it signiﬁ  cantly interfered with your social life, relationships, school work, 
job, or any other activities? Has it affected your family or friends?
Questions that are not recommended when screening for or diagnosing BDD:
1  It is recommended that patients not be asked if they are concerned with 
an ‘imagined’ defect in their appearance, whether they think they are ‘deformed’ or ‘disﬁ  gured’, or whether there is something ‘wrong with 
(their) body’
2  To diagnose BDD, it should not be required that patients refuse to accept 
the advice and reassurance of doctors that they do not have an abnormality5.2.8 body dysmorphic disorder

SECTION 5  psychiatry and medicine 1046
health care for other reasons. Using this diagnostic criterion will 
underdiagnose BDD. BDD is also underidentiﬁ  ed in many mental 
health databases because its ICD-9 diagnostic code identiﬁ  es it as 
hypochondriasis.
BDD usually goes undiagnosed in clinical settings.(3, 4, 22) Sufferers 
often conceal their symptoms due to embarrassment andshame.
(3, 4, 22) They may volunteer only depression, anxiety, or dis-
comfort in social situations. The compulsive and safety behaviours in Table 5.2.8.1 may be clues to BDD’s presence. BDD may be mis-diagnosed as another disorder
(3): social phobia or agoraphobia 
(due to secondary social anxiety and isolation), panic disorder (because panic attacks may occur after looking in the mirror or when feeling scrutinized by others), trichotillomania (when hair is cut or plucked to improve perceived ﬂ  aws, such as uneven eye-

brows), or OCD (due to obsessional preoccupations and compul-sive behaviours). Delusional patients are sometimes misdiagnosed with schizophrenia, psychotic depression, or psychotic disorder NOS. T o diagnose BDD, patients must usually be asked directly about BDD symptoms.
BDD has been reported in 0.7–1.7 pe r cent of co mmunity samples.(3)
In the largest study, a nationwide survey in Germany ( n = 2552), 
BDD was present in 1.9 per cent of women and 1.4 per cent of men.
(23) In smaller non-clinical student samples, BDD’s prevalence 
has ranged from 2.3–13 per cent.(3) A prevalence of 9–12 per cent 
has been reported in dermatology settings, 3–15 per cent in cos-metic surgery or plastic surgery settings, 8–37 per cent in patients with OCD, 11–13 per cent in social phobia, 26 per cent in trichotil-lomania, and 14–42 per cent in atypical major depression.
(3) In a

(3) In a 
study of 122 general psychiatric inpatients, 13 per cent had BDD’s, which was higher than for schizophrenia, OCD, PTSD, and eating disorders.
(22)
BDD’s pathogenesis is likely to be complex and multifactorial.(3)
Aetiologic factors likely involve a complex interplay of genetic and environmental risk factors.
(3) Preliminary data indicate an associa-
tion of the GABAA-γ2 gene with BDD. Environmental risk factors 
may include perceived childhood neglect and/or abuse, teasing, and low parental warmth. A role is also likely for socio-cultural and evolutionary pressures (e.g. symmetrical features may signal repro-ductive health).
Neuropsychological studies indicate a tendency to focus on 
isolated details of visual and verbal stimuli rather than more global, conﬁ  gurational attributes
(24)—consistent with clinical observa-
tions that patients selectively attend to speciﬁ  c aspects of their 
appearance or minor ﬂ  aws. Cognitive processing studies indicate

appearance or minor ﬂ  aws. Cognitive processing studies indicate 
that BDD patients tend to misinterpret ambiguous social (and other) situations as threatening and misinterpret self-referent facial expressions as contemptuous and angry.
(17, 18)  These interpretive 
biases may combine with rejection sensitivity, perfectionism, and a focus on aesthetics to contribute to BDD’s development.
(3) High 
neuroticism and low extroversion may also play a role.(3) Many 
potential risk factors (e.g. neuroticism) are not speciﬁ  c to BDD, 
but the overall combination of risk factors may be. BDD’s neurocir-cuitry is unknown but likely involves a complex interplay of  dysfunction in several neural systems,
(3,25) including circuitry

(3,25) including circuitry 
involved in OCD (orbitofrontal cortex, anterior cingulate cortex, caudate, thalamus). BDD’s shared features with other anxiety dis-orders and depression points to possible dysfunction in amygdala, prefrontal cortex, and anterior cingulate cortex. Brain regions involved in body image and facial emotion perception (e.g. right parietal cortex, amygdala, occipitotemporal cortex [e.g. fusiform face and extrastriate body areas]) may also be involved.
Prospective and retrospective studies indicate that BDD is usually chronic.
(5,13, 26) More severe BDD, a longer duration of BDD, and 
the presence of a personality disorder predict a lower probability of remission. However, when BDD is accurately identiﬁ  ed and 
its treatment optimized, the prognosis appears much more favourable.

Treatment
BDD’s treatment is described in more detail elsewhere, including in a guideline from the United Kingdom’s National Institute of Clinical Excellence (NICE).
(3, 21, 27, 28)  Serotonin-reuptake inhibi-
tors (SRIs, or SSRIs) and cognitive–behavioural therapy (CBT) are  currently recommended as the first-line treatments.
(3, 21, 27, 29)
Treatment studies are limited, and more research is needed. However, available data consistently indicate that a majority of patients improve with these treatments.
Surgical, dermatologic, and other cosmetic treatment
A majority of BDD patients seek often-costly cosmetic treat-ment.
(3, 8, 9, 13, 30)  Dermatologists and surgeons are most often con-

sulted, but any type of physician may be seen. It appears that most BDD patients are dissatisfied with such treatment.
(3, 9, 13, 30)
Occasionally, dissatisﬁ  ed patients sue, or are violent towards, the 
physician. Some patients perform their own surgery(3, 6)—e.g. cut-
ting open one’s nose with a razor blade and trying to replace nose cartilage with chicken cartilage in the desired shape.
Pharmacotherapy and other somatic treatments
All SRI studies to date indicate that SRIs are often efﬁ  cacious for 
BDD.(3, 21)  These studies include a placebo-controlled ﬂ  uoxetine 
study ( n = 67), a controlled and blinded cross-over study compar-
ing the SRI clomipramine to the non-SRI antidepressant desipra-mine ( n = 29), and open-label trials of ﬂ  uvoxamine, citalopram,

ing the SRI clomipramine to the non-SRI antidepressant desipra-mine ( n = 29), and open-label trials of ﬂ  uvoxamine, citalopram, 
and escitalopram ( n = 15–30). In these studies, 53 per cent to 73 
per cent of patients responded to the SRI. The cross-over trial found greater efﬁ  cacy for clomipramine than desipramine, sug-
gesting that SRIs may be more efﬁ  cacious than non-SRI antide-
pressants for BDD. This important ﬁ  nding is consistent with
clinical series and retrospective data suggesting that SRIs aremore efﬁ  cacious than a broad range of non-SRI medications for 
BDD.
(3, 21)
Response to an SRI usually develops gradually and may require 
up to 12–14 weeks of treatment (while reaching a relatively high dose) to be evident.
(3, 21) Although dose-ﬁ  nding studies are lacking, 
relatively high SRI doses (higher than typically used for depression)

1047
appear to often be needed.(3, 21) Response to medication usually 
includes a decrease in appearance preoccupations, distress, and compulsive/safety behaviours, as well as improved functioning. Suicidality, depressive symptoms, anxiety, and anger-hostility often improve.
(3) Of note, delusional patients often improve with SRI 
monotherapy, whereas limited data suggest that antipsychotic monotherapy is usually ineffective for delusional BDD.
(3, 21)
Patients who do not improve with one SRI may improve with 
another SRI.(3, 21)  Regarding SRI augmentation, a small double-
blind randomized controlled trial found that pimozide was not more efﬁ  cacious than placebo as a ﬂ  uoxetine augmenter.
(3,21)
Clinical series suggest that augmentation of an SSRI with buspi-
rone, lithium, or clomipramine may be helpful.(3, 21) (SSRIs may

(3,21)
rone, lithium, or clomipramine may be helpful.(3, 21) (SSRIs may 
increase clomipramine blood levels, however, which may cause tox-icity; thus, if this approach is tried, clomipramine should be started at a very low dose with monitoring of levels.) Clinical observations suggest that SSRI augmentation with venlafaxine, atypical neuro-leptics, or bupropion may be helpful for some patients.
(3, 21)
Monotherapy with agents other than SRIs has not been well 
studied.(3, 21) A small open-label trial ( n = 11) suggests that venla-
faxine may be efﬁ  cacious.(3) For severe and treatment-refractory 
cases an MAO inhibitor may be worth trying (but should never be combined with an SRI). Available case series and reports, while very limited, suggest that ECT is generally ineffective for BDD and secondary depressive symptoms.
(3, 21)
Clinical experience suggests that many patients relapse after SRI

(3, 21)
Clinical experience suggests that many patients relapse after SRI 
discontinuation and that long-term treatment may be needed, with efﬁ cacy usually sustained over time.
(3, 21) For patients who appear 
at high risk of suicide or violence, lifelong treatment with an effec-tive SRI is recommended, as suicides have been known to occur after SRI discontinuation.
Cognitive behavioural therapy (CBT)
Preliminary data suggest that CBT is often efficacious for BDD.
(3,27,29)  CBT typically includes:(3, 27–29)
1 Cognitive restructuring  to identify cognitive errors and develop 
more accurate and helpful BDD-related thoughts and beliefs
2 Behavioural experiments  to test the accuracy of BDD beliefs
3 Exposure  to avoided situations (e.g. leaving the house, attending 
social gatherings)
4 Response prevention  to decrease or stop compulsive behaviours 
(e.g. stopping excessive mirror checking, limiting grooming 
time)
In two randomized studies ( n = 54 and 19), patients improved

time)
In two randomized studies ( n = 54 and 19), patients improved 
more with CBT than on a waiting list.(3, 29)  Several case series 
(n = 5–13) found that CBT was efﬁ  cacious for BDD.(3, 29)  The num-
ber of sessions in these reports ranged from twelve 60-min sessions to sixty 90-min sessions.
Data on exposure and response prevention alone—without a 
cognitive element—is limited to a retrospective study and small case series with up to 10 subjects.
(3, 29)  These reports note favour-
able outcomes, although in the author’s experience cognitive approaches are a helpful, even necessary, component of treatment for most patients. It can be particularly helpful to work on core beliefs, which typically involve feelings of inadequacy and being unwanted by others.
(3, 9) Clinical experience additionally suggests

(3, 9) Clinical experience additionally suggests 
that the following are beneﬁ  cial components of CBT:(3, 28)1 Mirror retraining , which involves learning to see one’s entire body 
in a non-judgemental and ‘holistic’ way (rather than focusing on disliked areas), while refraining from excessive mirror checking
2 Habit reversal  for skin picking and repetitive hair pulling or 
plucking
3Mindfulness skills
4Activity scheduling  and scheduling pleasant activities  for more 
severely ill, depressed, and inactive patients
5 Motivational interviewing , which may be needed to engage and 
keep patients in treatment
Future studies (e.g. dismantling studies) are needed to determine 
which speciﬁ  c components of CBT are necessary and effective.
Other types of psychotherapy have not been well studied and are 
not currently recommended as ﬁ  rst-line treatments.
(3) Nonetheless,

(3) Nonetheless, 
clinical experience suggests that insight-oriented or supportive therapy—in addition to an SRI and/or CBT—may help some patients cope with their illness or with co-occurring problems or disorders.
(3)
Management approaches are described in more detail else-where.
(3, 21, 27, 28)
1 First try to engage the patient and establish an alliance so they 
are willing to try treatment. This can be difﬁ  cult to accomplish, 
as many patients are delusional, prefer cosmetic treatment, are rejection sensitive, and do not want other people (including a clinician) to see them.
2 Empathize with the patient’s suffering.3 Take patients’ appearance concerns seriously, neither dismissing

2 Empathize with the patient’s suffering.3 Take patients’ appearance concerns seriously, neither dismissing 
their concerns about how they look nor agreeing that there is something wrong with their appearance. Trying to convince patients (especially delusional patients) that their beliefs are irra-tional or that they look normal is usually not helpful.
4 Instead, focus on the potential for psychiatric treatment to 
diminish their distress and preoccupation and improve their functioning and quality of life.
5 Provide psychoeducation about BDD and recommend reading.
6 For patients who wish to pursue cosmetic treatments, explain 
that such treatment appears ineffective for BDD.
7 Provide education about recommended treatments. It can

7 Provide education about recommended treatments. It can 
be helpful to explain, for example, that SRIs are usually well tolerated, are not habit forming, appear to normalize the brain (and do not cause brain damage), and often diminish suicidal thinking in people with BDD. CBT is a practical ‘here-and-now’ treatment in which patients actively collaborate with the thera-pist and learn helpful skills by attending sessions and doing 
homework.
Treatment should be initiated with an SRI and/or CBT. SRIs are 
also the ﬁ  rst-line medication for delusional BDD. All severely ill 
patients, especially those who are highly suicidal, should, in the author’s opinion, receive an SRI. Patients with severe comorbid depression also warrant SRI treatment. Other comorbidity may warrant additional medication.5.2.8 body dysmorphic disorder

SECTION 5  psychiatry and medicine 1048
Before concluding that an SRI is ineffective, it should be tried for

12–16 weeks, reaching the highest dose recommended by the manufacturer or tolerated by the patient (if necessary) for at least 2–3 of those 12–16 weeks. If tolerated, higher doses than those rec-ommended by the manufacturer can be cautiously tried to obtain or optimize a response (excluding clomipramine). If this is not effective, an augmentation strategy or switching to another SRI is indicated. For patients who refuse or are ambivalent about treat-ment motivational techniques should be tried. Patients who are not improving with CBT may need more frequent sessions, longer sessions, or a change in the current CBT focus. At least 4–6 months of weekly or more frequent CBT sessions, plus daily homework, is generally recommended. More severely ill and delusional patients may require much longer or more intensive treatment. Maintenance/booster sessions following CBT may reduce relapse risk. It may be helpful to add CBT to an SRI, or vice versa, if either treatment alone is insufﬁ  cient.

For certain patients, adjunctive individual supportive therapy or 
family therapy may be helpful.
(3) Families can be an invaluable 
support and facilitate treatment.(3) Mental health professionals 
may need to interface with dermatologists, plastic surgeons, and other physicians from whom patients have requested or are receiving cosmetic treatment.
Because little is known about BDD’s pathogenesis and risk factors, the disorder cannot currently be prevented. However, BDD should be treated in its early stages, before it causes substantial morbidity or interferes with a child’s, adolescent’s, or young adult’s development.
Although this disorder has received far less investigation than many other serious mental illnesses, BDD research is rapidly advancing. It is important that clinicians screen patients for this often-secret disorder and be aware that it typically goes unrecognized in clinical settings, causing signiﬁ  cant morbidity. While much more research

is needed, available treatments are often very helpful for this distressing and often-disabling disorder.
Further information about BDD and its treatment is provided in references 
3, 27, and 28 below and at www.bodyimageprogram.com.
1. Morselli, E. (1891). Sulla dysmorphophobia e sulla tafefobia. Bolletinno 
della R accademia di Genova ,6, 110–9.
2. Phillips, K.A. (1991). Body dysmorphic disorder: the distress of 
imagined ugliness. The American Journal of Psychiatry ,148, 1138–49.
3. Phillips, K.A. (1996, 2005). The broken mirror: understanding and 
treating body dysmorphic disorder . Oxford University Press, New Y ork. 
Revised and Expanded Edition, 2005.
4. Phillips, K.A., McElroy, S.L., Keck, P .E. Jr., et al. (1993). Body 
dysmorphic disorder: 30 cases of imagined ugliness. The American 
Journal of Psychiatry ,150, 302–8.
5. Phillips, K.A., Menard, W., Fay, C., et al. (2005). Demographic

5. Phillips, K.A., Menard, W., Fay, C., et al. (2005). Demographic 
characteristics, phenomenology, comorbidity, and family history in 200 individuals with body dysmorphic disorder. Psychosomatics ,46, 317–32. 6. Fontanelle, L.F., T elles, L.L., Nazar, B.P ., et al. (2006). A 
sociodemographic, phenomenological, and long-term follow-up study of patients with body dysmorphic disorder in Brazil. International 
Journal of Psychiatry in Medicine ,36, 243–59.
 7. Phillips, K.A., Menard, W., Fay, C., et al. (2005). Psychosocial 
functioning and quality of life in body dysmorphic disorder. Comprehensive Psychiatry ,46, 254–60.
 8. Hollander, E., Cohen, L.J., and Simeon, D. (1993). Body dysmorphic 
disorder. Psychiatric Annals ,23, 359–64.
 9. Veale, D., Gourney, K., Dryden, W., et al. (1996). Body dysmorphic 
disorder: a survey of ﬁ  fty cases. The British Journal of Psychiatry ,169,
196–201.

196–201.
10. Perugi, G., Akiskal, H.S., Giannotti, D., et al. (1997). Gender-related 
differences in body dysmorphic disorder (dysmorphophobia). The
Journal of Nervous and Mental Disease ,185, 578–82.
11. Phillips, K.A., Menard, W., Pagano, M., et al. (2006). Delusional versus 
nondelusional body dysmorphic disorder: clinical features and course of illness. Journal of Psychiatric Research ,
40, 95–104.
12. Phillips, K.A. (2004). Psychosis in body dysmorphic disorder. Journal of 
Psychiatric Research ,38, 63–72.
13. Phillips, K.A. and Diaz, S. (1997). Gender differences in body 
dysmorphic disorder. The Journal of Nervous and Mental Disease ,
185, 570–7.
14. Phillips, K.A., Coles, M., Menard, W., et al. (2005). Suicidal ideation 
and suicide attempts in body dysmorphic disorder. The Journal of

and suicide attempts in body dysmorphic disorder. The Journal of 
Clinical Psychiatry
,66, 717–25.
15. Phillips, K.A. and Menard, W. (2006). Suicidality in body dysmorphic 
disorder: a prospective study. The American Journal of Psychiatry ,
163, 1280–2.
16. Cotterill, J.A. and Cunliffe, W.J. (1997). Suicide in dermatological 
patients. The British Journal of Dermatology ,137, 246–50.
17. Buhlmann, U., Etcoff, N.L., and Wilhelm, S. (2006). Emotion 
recognition bias for contempt and anger in body dysmorphic disorder. 
Journal of Psychiatric Research ,40, 105–11.
18. Buhlmann, U., Wilhelm, S., McNally, R.J., et al. (2002). Interpretive 
biases for ambiguous information in body dysmorphic disorder. CNS Spectrums ,7, 435–6, 441–3.
19. Sarwer, D.B. (2002). Awareness and identiﬁ  cation of body dysmorphic

19. Sarwer, D.B. (2002). Awareness and identiﬁ  cation of body dysmorphic 
disorder by aesthetic surgeons: results of a survey of American Society for Aesthetic Plastic Surgery members. Aesthetic Surgery Journal ,
22, 531–5.
20. Phillips, K.A., Menard, W., and Fay, C. (2006). Gender similarities 
and differences in 200 individuals with body dysmorphic disorder. 
Comprehensive Psychiatry ,47, 77–87.
21. Phillips, K.A. and Hollander, E. (in press). Treating body dysmorphic 
disorder with medication: Evidence, misconceptions, and a suggested approach. Body Image: An International Journal of Research.
22. Grant, J.E., Kim, S.W., and Crow, S.J. (2001). Prevalence and clinical 
features of body dysmorphic disorder in adolescent and adult psychiatric inpatients. Journal of Clinical Psychiatry ,62, 517–22.
23. Rief, W., Buhlmann, U., Wilhelm, S., et al. (2006). The prevalence of

23. Rief, W., Buhlmann, U., Wilhelm, S., et al. (2006). The prevalence of 
body dysmorphic disorder: a population-based survey. Psychological 
Medicine ,36, 877–85.
24. Deckersbach, T., Savage, C.R., Phillips, K.A., et al. (2000). 
Characteristics of memory dysfunction in body dysmorphic disorder. Journal of the International Neuropsychological Society ,6, 673–81.
25. Saxena, S. and Feusner, J.D. (2006). T oward a neurobiology of body 
dysmorphic disorder. Primary Psychiatry ,13, 41–8.
26. Phillips, K.A., Pagano, M.E., Menard, W., et al. (2006). A 12-month 
follow-up study of the course of body disorder. The American Journal 
of Psychiatry ,163, 907–12.
27. National Collaborating Centre for Mental Health. (2006). Core 
interventions in the treatment of obsessive compulsive disorder and body dysmorphic disorder (a guideline from the National Institute

1049
for Health and Clinical Excellence, National Health Service). British 
Psychiatric Society and Royal College of Psychiatrists, London. 
http://www.nice.org.uk/page.aspx?o=289817
28. Wilhelm, S., Phillips, K.A., and Steketee, G (in press). Cognitive-
behavioral therapy for body dysmorphic disorder: a modular treatment manual . Guilford Publications Inc., New Y ork.
29. Neziroglu, F. and Khemlani-Patel, S. (2002). A review of cognitive and 
behavioral treatment for body dysmorphic disorder. CNS Spectrums ,
7, 464–71.
30. Crerand, C.E., Franklin, M.E., and Sarwer, D.B. (2006). Body 
dysmorphic disorder and cosmetic surgery. Plastic and Reconstructive 
Surgery ,118, 167e–80e.
5.2.9 Factitious disorder 
and malingering
Factitious disorder
Patients with factitious disorder feign or simulate illness, are con-

sidered not to be aware of the motives that drive them to carry out this behaviour, and keep their simulation or induction of illness secret. In ofﬁ  cial psychiatric nomenclature, factitious disorder has 
replaced the eponym Munchausen syndrome, introduced by Asher
(1) to describe patients with chronic factitious behaviour. 
Asher borrowed the term from Raspe’s 1785 ﬁ  ctional German cav-
alry ofﬁ  cer, Baron Karl von Munchausen, who always lied, albeit 
harmlessly, about his extraordinary military exploits.
The criteria for factitious disorder in DSM-IV(2) are (a) the 
intentional production or feigning of physical or psychological signs or symptoms; (b) motivation to assume the sick role; and (c) lack of external incentives for the behaviour (e.g. economic

intentional production or feigning of physical or psychological signs or symptoms; (b) motivation to assume the sick role; and (c) lack of external incentives for the behaviour (e.g. economic 
gain, avoidance of legal responsibility, or improved physical well-
being, as in malingering) and lack of a better classiﬁ  cation for the 
In the last 10 years there has been increased interest in deception 
in medical practice, with speciﬁ  c focus on pathological lying 
and the diagnostic dilemmas in this ﬁ  eld: speciﬁ  cally, how to dif-
ferentiate between hysteria, factitious disorders, and malingering. Some of these topics will be discussed in the next section.
This chapter concentrates on factitious physical complaints; fabri-
cated psychological symptoms are considered under malingering.
Diagnostic problems
The DSM-IV criteria have recently come under attack. Turner(3)

has argued that criterion B (motivation to assume the sick role) has no empirical content and fulﬁ  ls no diagnostic function. He also 
argues that criterion A, the intentional production of physical or psychological signs or symptoms, emphasizes symptoms and cannot accommodate pseudologia fantastica (PF), voluntary false confessions, and impersonations. He concludes that the two crite-ria need reformulating in terms of lies and self-harm, respectively. Bass and Halligan
(4) have also suggested that because the conceptual justiﬁ  cation for factitious disorders is ‘empirically unsubstantiated’

(4) have also suggested that because the conceptual justiﬁ  cation for factitious disorders is ‘empirically unsubstantiated’ 
and the motivation for diagnostic purposes (conscious versus unconscious; voluntary versus involuntary) essentially unknowable, it seems reasonable to question the clinical status and legitimacy of factitious disorder. More recently there has been a resurgence of interest in pathological lying , because this is often 
easier to identify than, for example, the degree of ‘voluntariness’ or ‘motivation’ to attain the sick role (however that is deﬁ  ned).
Pathological lying (pseudologia fantastica): a key 
component of factitious disorder
It is possible to identify pathological lying if the clinician has 
sufﬁ cient information at his disposal (most often the medical

sufﬁ cient information at his disposal (most often the medical 
notes). If the patient reports, for example, that they are being treated for leukaemia, and when there is evidence that contradicts this, then this suggests dissimulation. On some occasions the patient will admit to lying, but this is rare.
Because pathological lying is often a key component in factitious 
disorders, evidence for it should be actively sought by the clinician. But what distinguishes the pathological liar from the person who just lies a lot? Dike et al.
(5) suggest that the diagnosis is made when

(5) suggest that the diagnosis is made when 
lying is persistent, pervasive, disproportionate, and not motivated primarily by reward or other external factors. They also suggest, however, that a key characteristic of pathological lying may be its compulsive nature, with pathological liars ‘unable to control their lying’ . Psychiatric conditions that have been traditionally associated with deception in one form or another include malingering, confabulation, Ganser’s syndrome, factitious disorder, borderline personality disorder and antisocial personality disorder. Lying may also occur in histrionic and narcissistic personality disorders. It is important to note however that pathological lying can occur in the absence of a psychiatric disorder, and that there may be different types of pathological lying, e.g. the beneﬁ  t fraudster and the stereo-
typical wandering Munchausen patient de scribe differe nt subgroups.

typical wandering Munchausen patient de scribe differe nt subgroups. 
Furthermore, it has been reported that up to 40 per cent of cases of pseudologia fantastica have a history of central nervous system 
abnormalities, which suggests that brain dysfunction in these patients requires closer study.
(6)
In recent years, functional neuroimaging techniques (especially 
functional magnetic resonance imaging) have been used to study deception. Attempted deception is associated with activation of executive brain regions (particularly prefrontal and anterior cingulate cortices), while truthful responding has not been shown to be associated with any areas of increased activation (relative to deception).
(7) Furthermore, Y ang et al.(8) reported that pathological

(7) Furthermore, Y ang et al.(8) reported that pathological 
liars showed a 22–26 per cent increase in prefrontal white matter and a 36–42 per cent reduction in prefrontal grey/white ratios compared with both antisocial controls and normal controls. These ﬁ ndings suggest that increased prefrontal white matter develop-
mentally provides a person with the cognitive capacity to lie, although Spence
(9) has urged caution in the interpretation of these 
results.
Clinical features of factitious disorder
Clinical features are diverse, and attempts to subtype patients have not always been helpful. The majority of patients with factitious dis-orders are non-wandering, socially conformist young women (often nurses) with relatively stable social networks.
(10–12) These patients 5.2.9 factitious disorder and malingering

SECTION 5  psychiatry and medicine 1050
are likely to enact their deceptions in general hospitals, especially 
accident and emergency departments, and the liaison psychiatrist should be alert to these clinical problems, which can be referred from a variety of different medical and surgical specialties.
Factitious disorders typically begin before the age of 
30 years;
(13, 14) there are often prodromal behaviours in childhood 
and adolescence (see below). These individuals often report an unexpectedly large number of childhood illnesses and operations, and many have some association with the health care ﬁ  eld.
(10) High 
rates of substance abuse, mood disorder, and borderline personality disorder have been reported.
(10,12) Approximately four-fifths 
of factitious disorder patients are women, and 20–70 per cent work in medically related occupations.
(12)
Clinicians should be alert to the presentation of more exotic

(12)
Clinicians should be alert to the presentation of more exotic 
forms of factitious presentation. For example, some women present themselves to family cancer or genetic-counselling clinics and provide a false family history of breast cancer to their medical attendants.
(15) Another recent example is ‘electronic’ factitious 
disorder,(16) used to describe patients who falsify their electronic 
medical records to create a factitious report (e.g. of cancer). Another important group is encountered in pregnancy, and this will clearly have important implications for child protection.
(17)
In medico-legal practice factitious disorders have been described 
in patients with a diagnosis of reﬂ  ex sympathetic dystrophy (RSD), 
specially involving the forearm,(18) and others have reported that

specially involving the forearm,(18) and others have reported that 
the abnormal movements commonly associated with RSD (CPRS Type I) are consistently of somatoform or malingered origin.
(19)
Cases have been described where patients involved in litigation have died of factors directly related to factitious physical disorder.
(20)
It is being increasingly recognized that these disorders can occur 
in childhood and adolescence, and child psychiatrists need to be alert to factitious presentations, especially in departments of infec-tious diseases.
(21) Unlike adult patients, many of these children 
admit to their deceptions when confronted, and some have positive outcomes at follow-up. The descriptions of some of these children as bland, depressed, and fascinated with health care are remarkably similar however to adults with factitious disorders.
(22)
Four main subtypes are distinguished in DSM-IV .(2)

(22)
1 Factitious disorder with predominantly psychological signs 
and symptoms. This is more difﬁ  cult to diagnose than factitious 
disorder with physical complaints, because there is no way of excluding a ‘true’ psychiatric disorder by physical examination or laboratory investigation: see below under malingering.
2 Factitious disorders with predominantly physical signs and 
symptoms. Almost every illness has been produced factitiously. However, four subgroups describe most cases
(23):
(a) self-induced infections(b) simulated illnesses, for example adding blood to urine
(c) interference with pre-existing lesions or wounds
(d)  surreptitious self-medication, for example self-injection of 
insulin
These categories are not mutually exclusive or jointly exhaustive.
3 Factitious disorders with combined psychological and physical 
symptoms4 Factitious disorders not otherwise specified. This includes

symptoms4 Factitious disorders not otherwise specified. This includes 
factitious disorder by proxy (see below and Chapter 9.3.3).
Diagnosis
Clinicians should become suspicious that a patient may be fabri-cating symptoms if the following features are noted:
◆ The course of the illness is atypical and does not follow the natu-ral history of the presumed disease, e.g. a wound infection does not respond to appropriate antibiotics (self-induced skin lesions often fall into this category, when ‘atypical’ organisms in the wound may alert the physician).
◆ Physical evidence of a factitious cause may be discovered during the course of treatment, e.g. a concealed catheter, a ligature applied to a limb to induce oedema.
◆ The patient may eagerly agree to or request invasive medical pro-cedures or surgery.

◆ There is a history of numerous previous admissions with poor outcome or failure to respond to surgery (these patients may overlap with the chronic somatoform patient with ‘surgery prone behaviour’).
(24)
◆ Many physicians have been consulted and have been unable to ﬁ nd a relevant cause for the symptoms.
Additional clues include the patient being socially isolated on the 
ward and having few visitors, or the patient being prescribed (or obtaining) opiate medication, often pethidine, when this drug is not indicated. When these ﬁ  ndings occur in someone who has 
either worked in or is related to someone who has worked in the health ﬁ  eld, the caregivers should have a high index of suspicion 
for a factitious disorder. Obtaining collateral information from family members, prior physicians, and hospitals is crucial.

Factitious disorder must be distinguished from authentic medical conditions. It is not uncommon in clinical practice however to ﬁ  nd 
patients with both  factitious disorder and coexisting physical 
illness. For example, patients with brittle diabetes are usually young females who deliberately interfere with their treatment, causing unstable diabetic control.
(25) A syndrome of severely unstable 
asthma (‘brittle asthma’) which also affects young females has also been described;
(26) this can occur (especially in A and E departme nts) 
with paradoxical adduction of the vocal cords during inspiration.(27)

Such patients can neglect to take medication at appropriate times and then ignore adequate management of the potentially danger-ous consequences. This may lead to repeated admissions to hospi-tal with medical emergencies such as diabetic ketoacidosis, status asthmaticus, or even pseudo status (simulated status epilepticus).
Factitious disorders are differentiated from somatoform disor-

ders, where physical symptoms, although not caused by physical disease, are deemed not to be intentionally produced. Patients with factitious disorder, although they may state that they are not aware of the motives that drive them, voluntarily produce their physical or psychological symptoms. The disorders may overlap, however, and non-wandering female patients with factitious physical disor-ders may have more in common with those females who have somatoform disorders than with men with factitious disorder or with malingerers. Fink
(28) found that 20 per cent of patients with

1051
persistent somatization (i.e. patients with more than six admissions 
to the general hospital with medically unexplained symptoms) also had a factitious illness. One of the authors (Christopher Bass) has also found coexisting chronic somatoform and factitious disorders in the female perpetrators of factitious or induced illness.
(29)
A more difﬁ  cult distinction is between factitious disorder and 
malingering. Malingerers, described below, have clear-cut goals, often personal proﬁ  t, and lack a history of hazardous, unnecessary 
invasive procedures. In our opinion the boundaries between the two disorders are more porous than the glossaries would have us believe, and we have stated above that the differentiation between conversion disorders, factitious disorders and malingering is extremely difﬁ  cult in clinical practice. Case reviews have demon-
strated how behaviour may shift from somatization to factitious to malingering when patients are followed longitudinally.
(30) In our

(30) In our 
opinion the clinical status and diagnostic legitimacy of factitious disorder as a selective medical disorder is questionable, because it fails to take account of a morally questionable but volitional-based choice to deceive others by feigning illness. Considered as an act of wilful deception, illness deception can be meaningfully conceptual-ized within a socio-legal or moral model of human nature that recognizes the capacity for choice and the potential for pursuing beneﬁ  ts associated with the sick role. This model, which recognizes 
the human capacity to exercise free will, is shown diagrammatically in Fig. 5.2.9.1.

Factitious disorders are relatively uncommon but probably underdiagnosed. Prevalence depends on clinical setting and the investigators’ index of suspicion. Factitious disorder (probably underreported) is probably more common than full-blown Munchausen syndrome (probably overreported). In a recent survey of physicians from Germany, frequency estimates of factious disor-der among their patients averaged 1.3 per cent, with dermatologists and neurologists giving the highest estimations.
(31)
Of 1288 liaison psychiatric consecutive referrals, seen in a North 
American general hospital, 0.8 per cent had factitious disorder.(13)
Similar ﬁ  gures have been reported by Dutch investigators.(14)Prevalence rates for factitious disorder with psychological symptoms 
in patients under the age of 65 in a psychiatric hospital are approx-imately 0.4 per cent.
(32)
Aetiology

(32)
Aetiology
There is little aetiological information, as large studies are lacking and the self-reported histories of many patients are fallacious. However, a number of themes are apparent
(13):
Developmental
◆ Parental abuse, neglect, or abandonment: Many factitious disor-
der patients experienced signiﬁ  cant deprivation in childhood 
that left them with unfulﬁ  lled cravings for attention and care. 
These patients then seek to gratify these dependency needs by creating illness to obtain the ‘attention and care’ of the medical system
◆ early experiences of chronic illness or hospitalization
Medically related
◆ a signiﬁ  cant relationship with a physician in the past
◆ experiences of medical mismanagement leading to a grudge 
against doctors
◆ paramedical employment
Physical
◆ Organic brain disorder: There is increasing evidence that neuro-

Physical
biological factors have a role in some patients, and it has been recommended that screening for evidence of brain dysfunction be carried out in these patients.
(33) It is thought however that it is 
the pseudologia fantastica, and not the factitious disorder per se, that is associated with brain dysfunction (see previous section on Pathological Lying), though such a distinction may be difﬁ  cult to 
support in clinical practice.
The authors have found it useful to conceptualize the problem 
using a cognitive behavioural formulation suggested by Fehnel and Brewer.
(34) This allows the assessors to examine for relevant 
developmental factors and recent life events (especially losses or threatened losses and separations; see Fig. 5.2.9.2).

Factitious disorder may be limited to one or more brief episodes, but is usually chronic. For example, of 10 patients identiﬁ  ed in a 
general hospital setting and followed up, at least one was known to have died as a result of factitious behaviour 4 months after the index admission.
(13) Only one of the remaining nine patients 
accepted psychiatric treatment after discharge from hospital. Other authors have, however, reported a less gloomy outcome.
(10)
Outcome may be determined by how patients are managed, once their deceptions become manifest. Regrettably, the unmasking of the disorder is often the end of the story. Psychological support following hospital discharge may be associated with improved outcome.
(10) Non-wanderers with more stable social networks may

(10) Non-wanderers with more stable social networks may 
have a better prognosis than wanderers.(14) Engaging a patient with 
factitious disorder in long-term psychological treatment occurs so rarely that it often becomes the subject of a case report. One such report, of a 20-year follow-up of a patient with factious disorder with a favourable outcome is, in the opinion of the authors, the exception to the rule.
(35)Fig. 5.2.9.1 Model of illness deception incorporating patient choice, free will and 
intentionality. (Reproduced from Bass, C. and Halligan, P . Illness related deception: social or psychiatric problem? Journal of the Royal Society of Medicine, 100, 81−4. 
Copyright 2007, The Royal Society of Medicine Press.)CHOICE
Intentional
Non-
intentionalPsychiatric/
PsychosocialdisordersDECEPTION
ExaggerationMalingeringConceptualising Illness Behaviour
Exculpated
Responsibility5.2.9 factitious disorder and malingering

SECTION 5  psychiatry and medicine 1052
Treatment
There are no systematic or controlled treatment studies on patients 
with factitious disorders. This is hardly surprising, as the patient’s 
primary motive is deception, and the doctor’s is to understand 
or unmask these motives, usually leading to rapid discharge from 
hospital after the deception has been exposed.
Once the diagnosis is established, the doctor–patient relationship 
may have become irreparably damaged: negative emotions in the 
doctor may need to be dealt with before any consideration can be 
given to ‘engaging’ the patient in any therapeutic endeavour. Ethical 
and legal issues may also intrude (see below) and affect manage-
ment. Although psychotropic medications have been used, the main treatment is psychological, using either confrontational or 
non-confrontational strategies.
Before treatment takes place however, it is important to establish 
the diagnosis, which is nearly always initially made by a non-

psychiatrist, e.g. A and E physician, infectious disease specialist. 
A meeting should take place between the physician/surgeon and 
the psychiatrist and a strategy worked out before any confrontation 
or other approach is embarked on. These preliminary procedures 
are important and preparation before the joint interview is crucial 
(Table 5.2.9.1).
(a) Confrontational approaches
This process is easier if the physician has tangible evidence of fabri-
cation, for example catheters, or medication used in the patient’s 
deception. It is also desirable to have the psychiatrist present when Fig. 5.2.9.2 A cognitive behavioural conceptualization of factitious disorder. Reproduced from Kinsella, P . Factitious disorder: a cognitive  behavioural perspective,

Behavioural Cognitive Psychotherapy ; 29: 195–202, copyright 2001, with permission from Cambridge University Press

1053
the physician confronts the patient. The approach during confron-
tation and thereafter should be non-punitive and supportive, stressing continuity of care, and that the patient is a sick person who needs help. This approach was adopted in perhaps the largest published series of patients with factitious disorder treated system-atically.
(10) Thirty-three patients were ‘confronted’ with objects 
found in their room or with clinical data showing that their condi-tions were factitious. Only 12 (36 per cent) patients acknowledged the truth; the remaining 21 continued to deny that they played any role in creating their disorders. No confronted patient developed serious psychological disturbance or became suicidal, or discharged themselves against medical advice. Four of the most chronic cases became asymptomatic. Most, however, greeted the idea with either overt hostility or passivity and covert negativism.
More recently Krahn et al.
(12) replicated these ﬁ  ndings, but found

(12) replicated these ﬁ  ndings, but found 
that only one in six of their patients acknowledged their factious behaviour. Many patients will experience confrontation as humili-ating and seek care from a different hospital. Others will refuse to see the psychiatrist with the treating clinician to discuss the decep-tion, and discharge themselves against clinical advice.
(b) Non-confrontational strategies
These approaches, advocated by Eisendrath and Feder,(36) are less 
concerned with the origin of the illness and more with shaping future behaviours. Face-saving is a key element, and it is important for the patient to subsequently explain their ‘recoveries’ without admitting that their original problems were psychiatric.
One strategy is the therapeutic ‘double-bind’ . In this approach the

One strategy is the therapeutic ‘double-bind’ . In this approach the 
patient is presented with two choices: prove that his or her disorder is not factitious by responding to a relatively minor and benign medical intervention, or prove that the disorder is factitious by fail-ing to respond. For example, a woman was offered the double-bind for a wound that had failed to heal in 4 years despite numerous sur-gical closures. Following this strategy the plastic surgeon told her that her wound should respond to a skin grafting procedure. If it did not, it would mean that her disorder was factitious in origin. 
The graft took place, and there was no recurrence of infection at 
2-year follow-up.
(36) This approach has also been used with some 
success in the rehabilitation of three patients with factitious motor disorders.
(37) The strategy was successful in providing patients with 
a face-saving legitimization of both their illnesses and recoveries.

Another face-saving approach uses ‘inexact interpretations’ , i.e. 
suggesting a relationship between certain events or stressors, for example being abandoned, and emergence of factitious symptoms. 
It involves presenting a brief formulation of the problem to the patient, stopping short of overtly identifying the factitious origin. By avoiding confrontation the doctor makes it safe for the patient to relinquish the symptom with a feeling of control. Regrettably, none of these non-confrontational techniques have been evaluated in a systematic fashion.
(c) Systemic interventions

Patients with factitious disorders can create havoc on medical and surgical wards. They often elicit negative and hostile emotions in general hospital staff, especially after the deception has been exposed. The psychiatrist can help staff members to vent and reduce the anger they experience when a factitious diagnosis is conﬁ  rmed, and also help the staff to understand the likely mecha-
nisms underlying the factitious behaviour. These issues are often best addressed at a multi-disciplinary staff meeting. The major task of this group, which should include a member of the hospital medico-legal department as well as the patient’s family doctor, is to develop practical treatment guidelines and to discuss the complex legal and ethical issues raised with factitious physical disorders. Some of these issues are discussed in the next section.
Ethical and legal issues

Patients with factitious disorders create unique ethical and medico-legal issues, some of which will be described below.
If no meaningful doctor–patient relationship exists or can be estab-
lished, it has been argued that the physician is not bound by ethical codes, and that drastic solutions such as keeping ‘blacklists’ and the use of a central register can therefore be justiﬁ  ed.
(38) Objections to 
these approaches include breach of doctor–patient conﬁ  dentiality 
and possible denial of treatment for genuine illness. Anyway, the use of aliases and poor record-keeping reduces the effectiveness of blacklists. Furthermore, physicians who disclose information without patient consent may have to justify the decision to their licensing body. In the United States, there is a consensus that dis-closure should only occur where there is a speciﬁ  c risk to the patient

and/or another party. In such situations, a multi-disciplinary staff meeting can help to develop treatment policy, and share responsi-bility for difﬁ  cult decisions (see above).
(b) Invasion of privacy
The medical literature contains many descriptions of how the diag-
nosis of factitious disorder was established following a search of 
the patient’s room or belongings. Some physicians, however, con-
sider that such behaviour infringes patients’ rights, and that no search should be undertaken without the patient’s knowledge and consent. One way of avoiding this dilemma is to make it clear to the patient that factitious disorder is among the differential diagnoses, and then request permission for a room search. If needles or syringes are discovered during the course of treating the patient, the ethical issue of invasion of privacy does not arise.
(c) Involuntary hospitalization or treatment

Because the patient with factitious disorder may engage in behav-iour that leads to permanent maiming or even death, it has been argued that in such cases a compulsory order may be used to pro-tect the patient from himself or herself. This will provide time for Table 5.2.9.1  Supportive confrontation: preparation and process 
(for non-psychiatrists)
◆ Collect ﬁ  rm evidence of fabrication, e.g. catheter, syringe, medication
◆ Discuss with psychiatrist (or hospital legal team if no psychiatrist available)
◆ Arrange meeting to marshall the facts; discuss strategy. Discuss with GP
◆  CONFRONTATION with patient should be non-judgemental, non-punitive, 
with . . . 
◆ Proposal of ongoing support/follow-up
◆  If patient is a health care worker, the doctor should discuss with his/her 
medical defence organization
◆ Discuss the outcome of the confrontation with the patient’s GP

◆  Document full record of the meeting and proposed outcome in patient’s 
notes5.2.9 factitious disorder and malingering

SECTION 5  psychiatry and medicine 1054
not only a more in-depth psychiatric assessment but also the 
 development of a more trusting relationship with a therapist. This is a contentious subject, but some case reports do indicate that extended involuntary hospitalization may result in therapeutic progress.
(39)
Induced factitious illness (Munchausen syndrome 
by proxy)
Meadow(40) ﬁ rst described this disorder as ‘the deliberate produc-
tion or feigning of physical or psychological symptoms or signs in another person who is under that individual’s care’ , which has recently been renamed fabricated or induced illness or FII.
(29) The 
perpetrator is usually the mother and the victim her child: the syn-drome is considered to be a form of child abuse. The parent’s aim is to have the child considered seriously ill: this may involve provid-ing false histories, poisoning, or persuading doctors to carry out invasive and potentially dangerous procedures.

Factitious disorder and FII can be interrelated. Psychiatrists (and 
general practitioners) should be aware of the implications of a diagnosis of factitious disorder for any children of the index patient. For example, 75 per cent of mothers of these children have a history of a factitious or somatoform disorder, and most meet criteria for personality disorder.
(41) With the birth of a child some mothers 
with pre-existing factitious disorder abandon dissimulation them-selves, only to extend it to the next generation through factitious disorder by proxy. Because factitious disorder and FII can co-occur, the ﬁ  nding of one should always trigger judicious efforts to estab-
lish, or hopefully disconﬁ  rm, the other.
Long-term outcome in factitious disorder by proxy is poor, so 
active early intervention is recommended, with child protection agencies working closely with paediatric and psychiatric services (see also Chapter 9.3.3).
Factitious disorder in health care workers

If factitious disorder is diagnosed in a health care worker, the inves-tigating psychiatrist should consider whether their continuing clin-ical work would pose risks to either patients (often children) with whom that person comes into contact (i.e. of factitious disorder by proxy), and/or the health of the factitious disorder patient him-self or herself. These issues have been thrown into sharp focus by some highly publicized cases in both the United States and the United Kingdom.
(42,43)  Any employee who manufactures crises, for

(42,43)  Any employee who manufactures crises, for 
example multiple cardiac arrests and resuscitations, is obviously of great concern. The British commission that investigated the 1993 case made several stringent recommendations, for example ‘We recommend that no candidate for nursing in whom there is evidence of major personality disorder should be employed in the profession’ .
(44) Nevertheless, psychiatrists should seek medico-legal 
advice before communicating concerns about such patients to any third party, including the employing hospital.
Malingering and exaggeration
Malingering is the deliberate simulation or exaggeration of physi-cal or psychiatric symptoms for obvious and understandable gain (e.g. ﬁ  nancial compensation, disabled status and beneﬁ  ts, avoid-
ance of criminal prosecution or conscription).Treating doctors have been understandably reluctant to diagnose 
malingering lest it adversely affect the patient. However, recent

malingering lest it adversely affect the patient. However, recent 
research indicates that it may not be uncommon, especially where ﬁ nancial rewards attach to disability status, such as beneﬁ  ts for 
sickness or compensation for injury. We here describe some types 
of malingering seen in psychiatry, and discuss newer specialist psy-
chological tools, especially symptom validity testing , which are 
emerging as useful additions to the overall assessment.
Deﬁ nition
Malingering is not coded as a mental disorder in either ICD-10 or 
DSM-IV , although in the latter it is denoted as an ‘additional condi-tion that may be the focus of clinical attention’ .
DSM-IV
(2) suggests that malingering should be ‘strongly sus-
pected’ when two or more of the following factors apply:

DSM-IV
1 medico-legal context2 antisocial personality disorder3 discrepancy between complaints and objective ﬁ  ndings
4 lack of co-operation with the assessment
This actually sets a very low bar: in effect, DSM advises it should 
be ‘strongly suspected’ in any disputed medico-legal case (where points 1 and 3 apply), but does not give guidance as to how this ‘suspicion’ should be followed up. The ICD-10 deﬁ  nition (‘the 
intentional production or feigning of either physical or psychologicalsymptoms or disabilities, motivated by external stresses or incen-tives’) is broad, but again does not give practical suggestions regard-ing assessment.
Malingering includes:
1 Pure malingering: complete fabrication of symptoms2 Partial malingering: exaggerating real symptoms or saying that 
past symptoms are continuing

3 False attribution: falsely saying that real health problems are due 
to a compensable accident or other circumstance
Until recently, there has been little systematic information on prev-alence, although it has generally been agreed that exaggeration of real symptoms is more common than outright faking expect them to dissimulate. Exaggeration, dissimulation, or feigning can be con-sidered one of several rational/economic/adaptive options open to patients when seeking health care and/or limited social and welfare resources.
Using the ‘Composite Disability Malingering Index’ Grifﬁ  n et al.
(45)
suggested that 19 per cent of disability claimants in the United

(45)
suggested that 19 per cent of disability claimants in the United 
States malingered to some degree. A recent study of 131 practicing members of the American Board of Clinical Neuropsychology pro-vided estimates of the prevalence of malingering and symptom exaggeration for a variety of different clinical conditions.
(46) In this 
study, estimates of the base rate of malingering/symptom exaggera-tion were calculated using over 33 000 annual cases seen by a group of clinical neuropsychologists. The reported base rates (when sta-tistically adjusted to remove for the inﬂ  uence of referral source) 
were 29 per cent for personal injury, 30 per cent in the case of disability or workers compensation, 19 per cent in criminal cases, and 8 per cent in medical or psychiatric cases. The same rates

1055
broken down by diagnosis revealed 39 per cent in the case of mild 
head injury, 35 per cent in ﬁ  bromyalgia and chronic fatigue, 
31 per cent in chronic pain, 15 per cent for depressive disorders, and 11 per cent in the case of dissociative disorders. In a separate review of 1363 compensation-seeking cases, Larrabee
(47) found similar 
ﬁ gures for mild head injury of 40 per cent. The use of symptom 
validity testing has conﬁ  rmed these high rates of exaggeration 
(see under ‘Psychological tests’). For example, about 42 per cent in the Canadian series of Richman et al .
(48) and about 60 per cent 
in the United Kingdom in a series studied by one of the authors (Gill et al. submitted for publication).
(a) Malingered neurosis: post-traumatic stress disorder
The archetypal disorder after trauma is post-traumatic stress disor-
der. Malingering of other disorders seen after trauma, notably depression is less frequent, conﬁ  rming malingerers’ preference for

der. Malingering of other disorders seen after trauma, notably depression is less frequent, conﬁ  rming malingerers’ preference for 
dramatic positive symptoms such as nightmares and ﬂ  ashbacks.
In 1983 Sparr and Pankratz
(49) described ﬁ  ve men who claimed 
to have been ‘traumatized’ in the Vietnam War; three claimed to have been PoWs. It turned out that none had been PoWs, four had never been in Vietnam and two had never been in the services. The patients were seeking the generous beneﬁ  ts, which the United 
States accords to ex-service (Veterans’ Administration) personnel. The key point in this paper was that the authors supplemented their 
clinical assessment by seeking external data , in this case service 
records; relying on clinical assessment alone would have led to wrong diagnosis. Seeking corroboration is vital in the assessment of possible malingering.
Rosen, in another classic paper, documented malingered PTSD

Rosen, in another classic paper, documented malingered PTSD 
in the case of the Aleutian Enterprise , a ﬁ sh-processing ship, which 
sank in the Bering Sea in 1990.
(50) Of the 31 on board, 9 were lost,

(50) Of the 31 on board, 9 were lost, 
2 went back to sea, and the remaining 20 sued. Nineteen (86 per cent) of these 22 survivors consulted psychiatrists or psychologists with the key features of PTSD. But this is much higher than the expected rates: most individuals exposed to a traumatic event do not develop PTSD. Even if they do, it resolves over a few weeks or months in many cases, whereas here the claimants’ symptoms did not show any tendency to resolve. Furthermore, they all had almost all of the classic features of the condition, in other words, they did not display the case to case variability, which would be expected in real individuals. Rosen documented that the patients had in fact ‘shared symptoms’ and had been ‘coached’ by their attorneys, some of whom had advanced the claimants money so they would not have to settle.

Most cases of suspected malingered post-traumatic stress disor-
der involve less dramatic civilian trauma, most commonly road accidents. Again, exaggeration of genuine symptoms is much more common than outright fabrication. For example, a person involved 
in a car accident, with apparently genuine phobic travel anxiety, 
may report that they have nightmares and ‘ﬂ  ashbacks’ , but their 
description of these experiences lacks vividness on close enquiry. 
Holistic assessment is vital; if a minor accident is to be accepted as 
causing a severe psychiatric condition such as PTSD, there must be some evidence of pre-existing vulnerability. Otherwise, the apparent result will be disproportionate to the cause, and the possible inﬂ  u-
ence of external incentives on symptom presentation will need to be considered.(b) Malingered psychosis

This disorder can occur in various circumstances, for example in homeless persons wishing to obtain shelter in hospital, in previ-ously psychotic inpatients whose discharge is imminent, in illegal migrants seeking to avoid deportation or in criminal defendants trying to avoid standing trial or to inﬂ  uence sentencing.
A (perhaps somewhat academic) distinction can be made 
between malingered and factitious psychosis, in that malingerers are conscious of their motivation, and their goal is not merely con-ﬁ ned to gaining patient status. However, the following description 
covers both. It is ‘positive’ symptoms, which are usually mimicked

covers both. It is ‘positive’ symptoms, which are usually mimicked 
(e.g. hallucinations). They are often dramatic or bizarre. Patients are keen to describe them at interviews, unlike, for example, most patients with schizophrenia. Symptoms are obvious during assess-ments, less so when the patient is unobserved. More subtle features of genuine psychosis, such as thought disorder and negative symp-toms, are absent. Florid hallucinations may be unaccompanied by delusions, which would be unusual in genuine psychosis.
For example, Jaffe and Sharma
(51) described nine defendants on 
serious criminal charges that developed uncommon symptoms such as coprophagia and ‘seeing little green men’ . Eight were judged to be malingering, and ﬁ  t to plead, based on evidence such as the

serious criminal charges that developed uncommon symptoms such as coprophagia and ‘seeing little green men’ . Eight were judged to be malingering, and ﬁ  t to plead, based on evidence such as the 
association between visual hallucinations and organic brain syndromes, of which there was no evidence on investigation. Malingering in forensic settings also includes feigned memory deﬁ cits, when isolated amnesia for an alleged crime would place 
malingering in the differential diagnosis. Forensic psychiatry is dealt with elsewhere in this book.
Ganser syndrome  does not appear in current classiﬁ  cations. It was 
originally described in prisoners, as comprising confusion and so-called ‘approximate answers’ (or Vorbereiden: Question : for example: 
how many legs has a horse? Answer : three). If true confusion (dimin-
ished level of consciousness) is present, the diagnosis is the cause of

ished level of consciousness) is present, the diagnosis is the cause of 
this. Approximate answers may be seen in several conditions, includ-ing mental retardation, organic brain disorders, and malingering; again, the diagnosis will be the underlying condition. The term Ganser syndrome has now largely and rightly been dropped.
(c) Malingered cognitive deﬁ  cit
Study of cognitive deﬁ  cits following brain injury has recently led to 
advances in understanding of malingering, through the develop-ment of special neuropsychological tests, especially effort testing , to 
gauge the effort the patient brings to cognitive testing. These tests seem likely to have broader application than just brain injury assessment.
Discussion of the question of malingering post head injury has 
until recent years been rich in opinion, though comparatively light on facts. Miller’s view,
(52) long inﬂ  uential, was that many patients

(52) long inﬂ  uential, was that many patients 
malingered their memory and other cognitive symptoms and that symptoms were in inverse proportion to injury severity and were only resolved with receipt of compensation. He used the term ‘accident neurosis’ . Mendelson, by contrast,
(53) found that disability 
continued after settlement in many patients, and inferred from this that disability was generally not malingered.
The question is obviously not capable of being resolved scien-
tiﬁ cally without data. But such data is now becoming available. 
Recent ﬁ  ndings however have supported Miller’s original observa-
tions that embellishment rises as injury severity decreases in a 5.2.9 factitious disorder and malingering

SECTION 5  psychiatry and medicine 1056
compensable context.(54) Moving forward from mere debate, the 
American Academy of Neuropsychologists recently published a consensus statement which concluded that ‘Symptom exaggera-tion or fabrication occurs in a sizeable minority of neuropsycho-logical examinees, with greater prevalence in forensic contexts’ , and that the use of effort testing is mandatory in neuropsycho-logical assessments.
(55)
In clinical assessment, immediate recall (e.g. digit span) is impor-

(55)
tant, as even organic amnesic patients (e.g. Korsakoff’s syndrome) perform normally; poor performance suggests that poor motiva-tion or malingering should be among the differential diagnoses. Claims of being unable to remember personal information (e.g. name and birthday, also preserved in organic amnesia), yet having been able to come to the assessment independently, are highly sug-gestive of malingering, but seen only in gross cases. However, these ‘bedside’ tests are only a guide: psychiatric assessment of brain injury patients is not complete without quantitative assessment of cognitive function, including effort testing (see below).
(d) Malingered physical disease

This usually presents either as a referral to a liaison psychiatrist, or in a medico-legal context. A frequent example is a patient with post-injury back or neck pain who is involved in litigation or seeking disability payments. Often, some form of accident has undoubtedly occurred, so the potential for initial physical injury is not in doubt; but the length and severity of symptoms, disability, and distress may seem out of proportion, and raise the possibility of malingering.
In a seminal paper, Richman
(48) administered effort testing to 
106 people claiming injury or sickness beneﬁ  ts. Forty-ﬁ  ve (42 per 
cent) failed. On one easy subtest, those who failed the effort test overall had a similar score on average to patients with dementia tested previously, even though none of them had a clinical diagno-sis of dementia. Schmand et al.
(56) found that 61 per cent of litigants

(56) found that 61 per cent of litigants 
after whiplash neck injury had evidence of underperformance on memory testing compared with 29 per cent of outpatient controls. The underperforming litigants scored as low as controls with deﬁ nite evidence of closed head injury.
Malingering should be distinguished from factitious disorder, and 
from other syndromes such as hypochondriasis, other somatoform disorders, and conversion/dissociation disorder. These distinctions may involve difﬁ  cult judgements such as how ‘intentional’ is the 
production of a symptom, or how ‘genuine’ it is. As an alternative, it has been suggested that such patients lie on a continuum between 
those in whom the production of symptoms is assumed to be wholly unconscious (conversion/dissociation disorder) and those in whom it is wholly conscious (malingering, factitious disorder).
However, use of the concept of the unconscious has to be very

However, use of the concept of the unconscious has to be very 
cautious when there are external incentives. It stretches credulity to think that a claimant would be conscious of there having been an accident so as to pursue litigation, and conscious that the outcome could include ﬁ  nancial compensation, but somehow unconscious 
that presentation of symptoms could form a desired link between 
the two.
It is possible that the emergence of effort testing may cast new 
light on the area of unexplained physical symptoms. For example, the concept of somatoform disorders assumes that the symptoms are not consciously produced. However, if large-scale studies reveal 
that a substantial proportion of somatoform patients turn out to fail effort tests, or in other words to display evidence of conscious symptom exaggeration, then the concept of somatoform disorders may need to be re-examined.

Doctors’ training and culture rightly encourage the treating physi-cian towards a generally trusting relationship with his patients. However, assumptions that patients’ accounts are generally trust-worthy and that malingering is rare are not appropriate if the main responsibility of the doctor lies elsewhere, for example, to the Court, if he is preparing an expert report.
Identifying ungenuine cases requires an enquiring approach, 
and the methodical use of all sources of information:
◆ awareness of the possibility of exaggeration or faking of symp-
toms
◆ neutral attitude
◆ open questions initially; use closed questions with caution
◆ unlikely questions (see below)
◆ mental state—changes appropriat ely as sensitive  topics discussed?
◆ informants (but they may also have vested interests)
◆ observation—overt (e.g. in a ward) or covert (e.g. video 
surveillance)
◆ medical records (and legal documents if applicable)
◆ look for consistency of accounts

◆ standard psychometric tests—consistency of results across 
measures
◆ specialist instruments: symptom validity tests
The medical notes should be read, ideally before interview, espe-
cially the general practice records, and any discrepancies noted for specific enquiry. Legal assessments, case papers and previous reports should be studied.
In the clinical interview, a neutral attitude is essential; a confron-
tational approach, even if malingering is strongly suspected, may cause further exaggeration of symptoms. Open questions should be used at ﬁ  rst. Closed questions should be avoided (e.g. ‘Do you

tational approach, even if malingering is strongly suspected, may cause further exaggeration of symptoms. Open questions should be used at ﬁ  rst. Closed questions should be avoided (e.g. ‘Do you 
ever get nightmares where you seem to re-experience the acci-dent?’). The careful use of unlikely questions can be useful. For example, in suspected malingered post-traumatic stress disorder the answer ‘Y es’ to the question ‘Have you had any problems with colour vision since the accident?’ would be suggestive, but would still need clariﬁ  cation with open questions. ‘I am now colour-blind’ 
might suggest malingering, but ‘Red makes me nervous—it was a red car which crashed into me’ might not.
Questions must be appropriate to the case, ideally prepared 
beforehand and introduced tactfully to prevent the patient feeling that the interviewer is attempting to ‘catch him out’ . The interviewer 
should look for the clinical characteristics of the particular malin-
gered disorder in question.

Surveillance by video or other means may be used by lawyers 
or insurers, although is seldom initiated by clinicians, for ethical reasons (except perhaps in suspected factitious disorder by proxy—see Chapter 9.3.3).

1057
Psychological tests
Since the last edition of this book, consensus has developed that 
symptom validity testing is essential in neuropsychology, that is, in the ﬁ  eld primarily concerned with memory problems and brain 
injury. The tests in practical use are in fact specialized memory tests, and it is likely that their use will be extended from head injury cases to other cases in which memory complaints occur (such com-plaints are in fact very common in patients with pain or distress for any reason). We are about to discuss what currently appear to be the leading symptom validity tests in UK neuropsychology, the Word Memory T est
(57) and the T oMM,(58) but ﬁ  rst we mention 
some other tests by way of historical background.
Inconsistent patterns of response on standard instruments (e.g.

Inconsistent patterns of response on standard instruments (e.g. 
high scores on one measure of depression and low on another) might be suggestive. However, this should not be overinterpreted, because there is substantial test–retest variation on many tests, and there is also variation between subscales on the same occasion. Certain subscales of the Minnesota Multiphasic Personality Index have been proposed as measures of tendency to malinger. Specialist instruments have been developed, for example the Structured Inventory of Malingered Symptoms,
(59) which identiﬁ  es features 
associated with malingering such as endorsement of rare symptoms, which occur only infrequently in clinical populations. However, consensus on such tests remains some way off and they are not in general use in the United Kingdom.
T ests for malingered memory deﬁ  cits present memory tasks, which

T ests for malingered memory deﬁ  cits present memory tasks, which 
appear difﬁ  cult but are in fact easy. For example, 50/50 psychiatric and 
10/16 mentally retarded inpatients were able to recall nine of the 15 items on the Rey 15-item.
(60) Forced choice testing (e.g. Portland Digit 
Recognition T est) is another approach. A sequence of digits is present-ed. Subjects must identify it among two further sequences, one identi-cal and the other different. By chance alone, they must score around 50 per cent on a large number of items, and so below chance scores (below 50 per cent) strongly suggest malingering.
(61) However, this is very 
gross, and will miss many cases where the degree of exaggeration is less. Again, these tests are not in general use in the United Kingdom.
In the United Kingdom, the Word Memory T est and the T oMM

In the United Kingdom, the Word Memory T est and the T oMM 
have become established as leading symptom validity tests in neuropsychology. They are regarded as having the best research support and are administered in standard formats.
TOMM stands for Test Of Malingered Memory .
(58) It is a pictorial 
test, not computerized, and is mainly used by psychologists. Word Memory T est (WMT) (Green: wordmemorytest.com) is available either on paper or on computer. It is mainly used by psychologists as part of a ‘battery’ of neuropsychological tests. An abbreviated form for physicians, the Medical Symptom Validity T est, is available.
(57)
The key point is that patients are given a test of memory, which looks difﬁ  cult, but is in fact known to be easy from previous admin-
istration to control subjects.
Someone making a good effort:

◆ scores well on tests which are in fact easy (even though they may 
look hard)
◆ scores lower on more difﬁ  cult tests
Someone making an inconsistent or poor effort :
◆ may score low on tests which look hard (though they are in fact 
easy)
◆ may not score lower on more difﬁ  cult testsIf the patient’s scores are low, where even say primary school

easy)
◆ may not score lower on more difﬁ  cult testsIf the patient’s scores are low, where even say primary school 
children score almost perfectly, it would suggest that he might not have been making a full effort on the test. If at the end of the test he said that he had made a full effort, this would be evidence that his self-report of effort brought to cognitive testing is not accurate. This would be consistent with the proposition that he might have been exaggerating at least the memory aspects of his complaints, and by extension, possibly other symptom areas also.
Aetiology
Malingering is not a mental disorder, so complex general theories about causation are unlikely to be helpful. It has been suggested for example that
(62) ‘adaptation’ is the simplest model for malin-

gering: ‘ . . . malingering is more likely to occur when the evalua-tion is perceived as adversarial, when the personal stakes are very high, and when no alternatives appear to be viable’ . However, this really just restates the problem in different terms. Nor do the ‘response styles’ described by psychologists seem to offer funda-mental insights. It is more helpful to consider each case in a  common sense way, bearing in mind the presence or absence of external incentives, and the results of the holistic assessment pro-cess outlined above, in combination with the results of symptom validity testing.
Malingerers are so heterogeneous that it is impossible to state prog-nosis in general. There are few adequate follow-up studies.

In forensic and inpatient settings , malingering is usually episodic, 
associated with particular circumstances such as impending discharge, trial, or change in conditions of imprisonment (e.g. transfer to a single cell or hospital wing). The behaviour often stops when the circumstances no longer remain, although they may recur. Similar situations occur in persons facing conscription, or in migrants at risk of repatriation.
The prognosis of malingering in personal injury litigants  is 
unknown. Studies indicating poor outcome of many compensated litigants cannot be extrapolated, as the number of malingerers in these samples is unknown. Clinical experience suggests that patients with long-standing disability, even if partly or wholly non-organic, 
often fail to recover fully in any event.
Treatment

Treatment
There is very little evidence on management, which will largely be 
dictated by whether the clinician has clinical responsibility, or whether he or she has been asked to give an opinion to a third party. Even if the diagnosis of malingering is clear, it may be appropriate to inform the referrer, rather than the patient directly, as the patient may become very angry. If there is a psychiatric disorder present when, as it were, the dust has settled, then this should be treated in standard fashion.
Clinical experience is that patients for whom the exercise of 
attempted malingering seems worthwhile do often have substantial pre-existing psychosocial problems, including lack of skills or employment; there is a tendency towards a regionality of such claims, with areas of deprivation (‘rust-belt’) overrepresented.
Efforts at retraining and vocational rehabilitation may be more

Efforts at retraining and vocational rehabilitation may be more 
likely to be of assistance in the long-term than specialist psychiatric care.5.2.9 factitious disorder and malingering

SECTION 5  psychiatry and medicine 1058
These seem mainly conﬁ  ned to malingering after injury. First, 
systems of litigation should be expedited. Prolonged cases certainly make for exaggeration of symptoms and disability. Second, some patients with chronic disability, irrespective of cause, do respond to rehabilitative treatment (e.g. programmes assisting in return to work or in the management of chronic pain), even at a late stage. If such programmes were easily and generally available at an earlier stage in the evolution of the disorder, symptoms and subsequent disability could certainly be ameliorated or even prevented in some patients.
Ethical legal and personal issues
As previously indicated, malingering poses a number of particular challenges to the doctor himself and to the doctor–patient relation-ship, including amongst others the following.
There is no doubt that seeing substantial numbers of likely

There is no doubt that seeing substantial numbers of likely 
ungenuine patients has the potential to affect the practitioner 
himself. Appropriate ‘supervision’ , as in psychotherapy, may be appropriate.
If the doctor has a treatment responsibility to the patient, he 
naturally tends to give the patient the beneﬁ  t of doubt, for example 
in respect of disability payments. But he will be wise to be cautious: if, for example, he signs a form saying that the patient cannot undertake certain activities of daily living, but without direct observation of that, he could potentially be considered to be an accessory if the claim was subsequently found to be fraudulent.
The use of the word ‘malingering’ itself in reports must usually 
be avoided, as it is tantamount to an accusation of a criminal offence such as deception. The medical duty is to present the evi-dence to the Court, which can then decide the question itself.
Finally, it must not be forgotten that the Data Protection Act

Finally, it must not be forgotten that the Data Protection Act 
gives patients the right to see personal information about themselves such as medical reports. Any suggestion of ungenuine presentation in reports must therefore be well-founded on evidence and prop-erly argued.
Malleson, A. (2002). Whiplash and other useful illnesses . Magill-Queens 
Halligan, P ., Bass, C., and Oakley, D. (2003). Willful deception as illness 
behaviour. In: Malingering and illness deception  (eds. P . Halligan, 
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5.2.10 Neurasthenia
The term neurasthenia has had a variegated history, and although 
retained as a diagnostic entity in the ICD-10 it does not appear in the DSM-IV . In cultures where neurasthenia still enjoys popular professional and lay acceptance it has a variety of usages:

◆ a nosological entity
◆ an idiom for expressing distress
◆ a culturally sanctioned illness behaviour
◆ an explanatory model for a constellation of somatic symptoms
◆ an euphemism for avoiding the stigma of mental disorder.
Therefore, in diagnosing, understanding, and managing neuras-
thenia the clinician has to be aware of the context in which the term is used.
Concept and diagnostic entity

The concepts of nervous weakness and asthenia (debility, lack of strength) have existed throughout the history of medicine. Hippocrates described the illness of the Scythians as a general asthenia linked to damage to the genitalia caused by horseback rid-ing. In France, Bouchut (1764) described a syndrome similar to the latter-day neurasthenia, which he called ‘neuropathie’ . Cullen (1772) conceived muscles and nerves as a unitary nervous force and all diseases as movements against the nature of that nervous force. He coined the word neuroses for this process and postulated that diseases were due to the various alternations of excitement and atony in the nervous system. A few years later, his pupil Brown (1780) elaborated on the hypothesis by dividing diseases into sthenic diseases, which were due to excessive excitement, and asthenic diseases, which were due to deﬁ  cient excitement. These

views on the polarity of the nervous system as a cause of mental illness set the scene for neurasthenia to become a disease entity.5.2.10  neurasthenia

SECTION 5  psychiatry and medicine 1060
By the beginning of nineteenth century the term neurasthenia 
was already in use. In 1869, Van Deusen in Holland published a monograph on neurasthenia. This was quickly followed by the publication of a paper, which Beard
(1) had presented to the New York 
Medical Journal Association. Beard based his description of the disorder on a series of 30 cases. In reorganizing the subjective nature of the complaints and the unique clustering of symptoms in each patient, Beard had difﬁ  culties in attempting to limit the 
number of symptoms that constituted the syndrome; he started with 50 symptoms and expanded it to 75 in later publications.
Eventually it became clear that the expanding kaleidoscope of

Eventually it became clear that the expanding kaleidoscope of 
symptoms should be managed in a way that made some sense. Beard approached this problem by organizing the symptoms into subtypes of neurasthenia: cerebrasthenia (cerebral exhaustion) characterized by symptoms that were directly or indirectly con-nected with the head; myelasthenia (spinal exhaustion) was deﬁ  ned 
by symptoms related to the involvement of the spinal cord; diges-tive asthenia was characterized by dyspepsia, constipation, and ﬂ atulence. As time went on more subtypes were added by other 
investigators and speciﬁ  c treatment approaches were developed.
Despite the over inclusiveness of the term, Beard maintained that

Despite the over inclusiveness of the term, Beard maintained that 
neurasthenia belonged to one family with a common pathology, prognosis, history, and treatment. As more cases were reported, he felt able to claim that neurasthenia was predominantly an American illness.
(2) He attributed the increase in prevalence to the pressures 
of modern civilization.
Notwithstanding its vagueness, or perhaps because of its vague-
ness, neurasthenia gained popular acceptance not only by the med-ical profession but also by the general public. Although by the turn of the century it had become practically a household word, its pop-ularity did not preclude dissent. Most of the criticisms focused on the disorder’s over inclusiveness and lack of precision; for instance, Brill called it ‘the newest garbage can’ in medicine.
The ﬁ  rst two decades of the twentieth century witnessed an

The ﬁ  rst two decades of the twentieth century witnessed an 
increasing number of discoveries of more speciﬁ  c causes of disease. 
This period also saw greater attention being paid to the taxonomy of neuroses. These forces combined to bring about the decline of neurasthenia as a diagnostic entity.
In 1895, Freud published two seminal papers in which he drew 
up the blueprint for reconﬁ  guring the various neurotic disturbances 
that were grouped together under the term neurasthenia. In the paper entitled ‘On the grounds for detaching a particular syndrome from neurasthenia under the description of ‘anxiety neurosis’
(3)
he questioned the validity of continuing to allow neurasthenia to cover all the symptoms described by Beard. He saw the need to classify different categories of neuroses based on the following:
◆ collection of symptoms that were more closely related to one 
another
◆ common aetiology
◆ common psychical mechanism.

another
In the paper ‘Obsessions and phobias: their psychical mechanism 
and their aetiology’ ,(4) Freud removed obsessions and phobias from 
neurasthenia. As a result of these two papers, neurasthenia ceased to be an amorphous concept and was differentiated into the following categories:
◆ neurasthenia proper
◆ anxiety neuroses◆ obsessions
◆ phobias
◆ pseudoneurasthenias due to cachexia, arteriosclerosis, early 
stages of the general paralysis of the insane, and psychoses.
Intermittent and periodic types of neurasthenia were to be 
included under melancholia.
The ﬁ  rst list of symptoms Freud proposed for neurasthenia prop-
er included headache, spinal irritation, dyspepsia with ﬂ  atulence, 
and constipation. Later, he added sexual weakness and fatigue.
The possibility of including some neurasthenic symptoms under

The possibility of including some neurasthenic symptoms under 
melancholia was mentioned but not expanded on by Freud. This task was taken up by Kraepelin.
(5) He distinguished three major 
types of depression: manic–depressive disorder, involutional melancholia, and a milder form of neurasthenic depression. He asserted that all these types of depression were due to an underly-ing disordered brain function.
Having been so denuded, the use of the term neurasthenia 
as a diagnostic entity by the medical professions had declined in the United States by the time of the First World War. The ﬁ  rst

as a diagnostic entity by the medical professions had declined in the United States by the time of the First World War. The ﬁ  rst 
edition of the DSM-I published in 1952 gave no formal recogni-tion to neurasthenia. Instead, it was replaced by the category of ‘Psychophysiological nervous system reaction’ , the predominant symptom of which was general fatigue. In an effort to make DSM-II congruent with ICD-8, neurasthenia reappeared in American psychiatry as neurasthenic neurosis.
In DSM-III neurasthenia disappeared as an entity and appeared 
only in the index where readers were asked to refer to ‘Dysthymic disorder’ . However, unlike the DSM classiﬁ  cation, neurasthenia 
consistently remained a subtype of neurosis throughout the many versions of the ICD. ICD-9 deﬁ  ned neurasthenia as follows.
A neurotic disorder characterized by fatigue, irritability, headache,

A neurotic disorder characterized by fatigue, irritability, headache, 
depression, insomnia, difﬁ  culty in concentration, and lack of capacity 
for enjoyment (anhedonia). It may follow or accompany an infection or exhaustion or arise from continued emotional stress.
The following categories were included:
◆ fatigue neurosis
◆ nervous disability
◆ psychogenic asthenia
◆ general fatigue.
Spread to other countries
One of the most fascinating aspects of the history of neurasthenia is its ready acceptance by countries other than the United States where it was originally conceived as a peculiarly American phe-nomenon. The diagnostic entity took ﬁ  rmer root in some countries 
than in others. In many countries the concept was indigenized and took on local cultural colour.
The reasons for its spread can be summarized as follows:

◆ The all-embracing nature of the entity provided a foothold for 
almost everyone involved.
◆ The concept provided a blend of scientiﬁ  c theory, thus lending 
legitimacy to a cluster of symptoms, which are mostly subjective.
◆ It is considered to be a disease resulting from overwork, which 
affects the upper social class.

1061
Asia and Australia
In all probability neurasthenia was introduced into China in the 
1920s by American psychiatrists and returning Chinese doctors who were trained in the United States. Up to the end of the Second World War, Chinese physicians accepted and used the diagnostic concept of neurosis and neurasthenia from the United States. With the ﬁ  rm establishment of communism in 1949, Pavlovian theory 
was adopted as the sole model on which Chinese psychiatrists practice, teach, and research.
(6) In China, as in the former USSR, 
neuroses were divided into neurasthenia, psychasthenia, and hysteria. The cause of neurasthenia, as indeed of neuroses, followed the Pavlovian theory of overstrain in the excitation and inhibition processes and mobility of the higher nervous system.
The concept of neurasthenia or shenjing shuairuo  (nerve weakne ss),

The concept of neurasthenia or shenjing shuairuo  (nerve weakne ss), 
as translated by the Chinese, was not an entirely alien idea. The symptoms associated with neurasthenia (fatigue, loss of memory, poor attention span, headache, tension, insomnia, and all varieties of vague pains) are similar to those in patients suffering from a deﬁ ciency in qi (vital essence), that is weakness of the kidney, 
spleen, or heart in traditional Chinese medicine. In addition, the theory of nerve weakness and depletion of nervous energy as causes of neurasthenia ﬁ  ts in with the traditional Chinese medicine 
concept of organ weakness and yin–yang  deﬁ ciency. Thus in no 
time at all neurasthenia was incorporated into the body of the 
practice of traditional Chinese medicine and the vocabulary of the lay public.
In the 1950s, the number of patients suffering from neurasthenia

In the 1950s, the number of patients suffering from neurasthenia 
increased enormously. Medical or neurology clinics reported that 80 to 90 per cent of their outpatients were suffering from neurasthenia. It was particularly rampant among the ‘brain or mind workers’ . The Chinese government regarded it as a serious public health problem, so much so that in its First Five Y ear Plan (1958–1962) a large-scale national campaign was initiated to eradicate neurasthenia. Research on neurasthenia carried out during this period focused on the role of stress as the external factor, and on heredity and personality as endogenous factors. Treatment included intensive group re-education, herbal medicine, and tranquillizers. Lin
(7) postulated that the

(7) postulated that the 
marked increase in neurasthenia was due to the presence of a deep-seated tension in the revolutionary development of China during the 1950s. Neurasthenia became the vehicle to express political, social, and physical stresses.
About a decade after China’s ‘open-door policy’ , an epidemio-
logical survey was conducted in 12 districts in China. The instru-ment used was the Present State Examination. The results showed that neurasthenia affected 12.59 per cent of persons aged from 15 to 59 years, accounting for 56.7 per cent of all neurotic disorders.
(8)
In 1982, Kleinman(9) conducted a study of 100 patients diagnosed 
with neurasthenia in the Psychiatric Outpatient Clinic of the Hunan Medical College. He found that 89 patients satisﬁ  ed the

(8)
with neurasthenia in the Psychiatric Outpatient Clinic of the Hunan Medical College. He found that 89 patients satisﬁ  ed the 
DSM-III diagnostic criteria for ‘Major depressive disorder’ , 70 per cent of whom responded substantially to antidepressant medication. Despite their improvement, few experienced decreased help-seeking behaviour. This led him to conclude that neurasthe-nia should be regarded as a special form of somatization related to culturally sanctioned idioms of distress.
In Taiwan, neurasthenia attracted little interest among western-
trained doctors. However, it became enormously popular among traditional Chinese doctors, and consequently neurasthenia established itself as a major disease in the minds of the Taiwan 
public during the 1940s and 1950s.
(10)
The mostly British-trained doctors in Hong Kong largely ignored

(10)
The mostly British-trained doctors in Hong Kong largely ignored 
neurasthenia as a diagnostic entity. As in Taiwan, neurasthenia became the domain of traditional Chinese doctors.
(11)
In the late nineteenth century psychiatry in Japan was essentially 
German in orientation. Psychiatrists applied the diagnosis of neurasthenia to patients who presented with weakness, headaches, mental distraction, fatigue, and reduced psychic productivity.
(12)
The diagnostic entity became a popular term until Morita(13)
supplanted it with the term shinkeishitsu  (nervous or nervous dis-
position). He described this disorder as basically a psychological reaction to anxiety in predisposed personalities—the personality type being characterized by introversion, perfectionism, hypo-chondria, hypersensitivity, and self-consciousness. He developed a speciﬁ  c treatment aimed at breaking up the vicious cycle of sensi-

tivity and anxiety, the initial phase of which consisted of isolated bed rest followed by a second phase of work therapy.
Doctors in Malaysia, Singapore, India, Pakistan, Burma, and Sri 
Lanka are mostly trained in the British tradition. After the First World War neurasthenia lost its popularity in Britain. Standard British textbooks regarded the disorder as rare and outmoded. As a result psychiatrists in these countries tended not to diagnose neurasthenia. However, neurasthenia is used in the Chinese com-munities where traditional Chinese medicine maintains a strong-hold. In India and countries where Ayurvedic medicine is practised, neurasthenia was not added on to the more traditional ways of explaining fatigue, pain, dizziness, and headaches. Instead, concepts such as dhàtu  loss (loss of semen) and vàta roga  (wind disease) 
remained the preferred explanation.
In Australia, Paterson
(14) reported that over a 15-year period

(14) reported that over a 15-year period 
from 1950 to 1965 neurasthenia was one of the 10 major illness categories reported by a large Sydney-based industry. He claimed that, since he had a fairly representative sample, the 10 categories of illness could very well apply to the rest of Australia.
Europe
From 1880 to 1920 neurasthenia was one of the diseases most frequently discussed. From an ‘American nervousness’ it rapidly evolved into a western European bourgeois illness. Practically every academic neurologist and psychiatrist wrote a major piece on neu-rasthenia (see Drinka
(15)).
In England, neurasthenia was described in Osler’s The Principles 
and Practice of Medicine  published in 1900.(16) During the First

(15)).
and Practice of Medicine  published in 1900.(16) During the First 
World War it was a common diagnosis used for invaliding out many soldiers. In order to cope with its diagnosis, treatment, and disposal, the Army instituted a short course of training for medical ofﬁ cers who graduated with the title of ‘neurasthenic expert’ (see 
Sims
(17)).
Russian psychiatry is largely based on Pavlovian psychophysio-
logical theories. The Pavlovian classiﬁ  cation of the principle of 
neuroses was adopted by all countries that came under the inﬂ  uence 
of the former USSR. Opinions on the subdivisions of neurasthenia were divided in Russia. One school of thought based its classi-ﬁ cation on the course of the illness, and the other was based on 
aetiology.
(18) Neurasthenia as a cause of inefﬁ  ciency and low pro-
ductivity in the workplace was a recurrent theme in both Russia and Eastern Europe.5.2.10  neurasthenia

SECTION 5  psychiatry and medicine 1062
Current usage
In ICD-10,(19) neurasthenia is classiﬁ  ed as a neurotic disorder in 
which two main, but overlapping, types of neurasthenia are described:
◆ the predominant symptom is increased fatigue after mental 
effort
◆ predominant feelings of bodily or physical weakness and exhaus-
tion after only minimal efforts.
For a deﬁ  nite diagnosis ICD-10 requires the following:
(a)  e ither persistent and distressing complaints of increased 
fatigue after mental effort, or persistent and distressing com-plaints of bodily weakness and exhaustion after minimal effort;
(b) at least two of the following:
◆ feelings of muscular aches and pains
◆ dizziness
◆ tension headaches
◆ sleep disturbances
◆ inability to relax
◆ irritability
◆ dyspepsia;
(c)  any autonomic or depressive symptoms present are not suf-
ﬁ ciently persistent and severe to fulﬁ  l the criteria for any of 
the more speciﬁ  c disorders in this classiﬁ  cation.
The following are excluded:

◆ asthenia not otherwise speciﬁ  ed
◆ burn-out
◆ malaise and fatigue
◆ postviral fatigue syndrome
◆ psychasthenia.
DSM-IV does not include neurasthenia as a nosological 
entity. Instead, it is replaced by ‘Undifferentiated somatoform 
disorder’ .
In the third edition of the Chinese Classification of Mental 
Disorders(20)neurasthenia is classiﬁ  ed under ‘Neurotic disorder’ . 
The criteria for diagnosis have been made more stringent, requir-ing three symptoms out of ﬁ  ve non-hierarchical groups of symp-
toms, which include weakness, emotionality, excitement, nervous pain, and sleep disturbance. The duration of the symptoms should be at least 3 months. Other psychiatric disorders have to be excluded. Because of the different connotations of fatigue and weakness in Chinese culture, fatigue is not included in the list of symptoms.
(21)

(21)
Fatigue is a ubiquitous symptom. It can occur in many psychiatric illnesses and in a wide range of physical illnesses. In cultures where the term neurasthenia is loosely used, many of the cases would probably meet the ICD-10 or DSM-IV diagnostic criteria for depressive disorder or anxiety disorder. Physical illness is a common cause of fatigue. In this respect, a detailed history and 
judicious investigation will be necessary.
Merikangas and Angst(22) studied a cohort of young adults from a 
community sample in Zurich, Switzerland, and reported the preva-lence of neurasthenia, deﬁ  ned according to the ICD-10 criteria, as 
1 per cent across 10 years. The sex ratio across the 10 years of follow-up revealed an equal prevalence among males and females during the initial stages of the study, but females exhibited an l.6-fold greater rate than males during the later stages.
The World Health Organization (WHO) international study
(23)

(23)
of patients with psychological problems seen in primary-care settings reported a prevalence of 1.7 per cent of pure neurasthenia. The prevalence rate increased to 5.4 per cent when the syndrome was diagnosed comorbid with depression or anxiety. The preva-lence rate in each centre is shown in Table 5.2.10.1.
The differences in the prevalence rate can be due to many factors, 
including perception of what health services can treat and the exist-ence of alternative sources of care.
The results of an epidemiological study conducted in 1998 in 
seven areas in China showed a prevalence rate of 2 per cent.
(24)
In a national survey by the Australian Bureau of Statistics Hickie 
et al.(25) reported that 1.5 per cent of the general population met 
the ICD-10 criteria for neurasthenia in the past year.
All the studies were consistent in demonstrating that the syndrome

All the studies were consistent in demonstrating that the syndrome 
tended to affect patients below the age of 45 and the absence of signiﬁ  cant gender differences.
Aetiology
Although theories abound, the predisposing, precipitating, and 
perpetuating causes of the syndrome remain unclear.
Table 5.2.10.1  Prevalence of neurasthenic syndrome among 
patients contacting general health care facilities
Centre Overall prevalence (%) Males (%) Females (%)
Ankara 4.1 1.0 5.6
Athens 4.6 3.3 5.2Bangalore 2.7 1.7 3.7Berlin 7.4 4.0 9.7Mainz 7.7 7.4 8.0Groningen 10.5 7.1 12.8Ibadan 1.1 3.4 0.2Manchester 9.7 6.1 11.3Nagasaki 3.4 3.8 3.0Paris 9.3 5.0 14.2Rio de Janiero 4.5 2.3 5.3Santiago 10.5 6.4 12.1Seattle 2.1 2.3 2.0Shanghai 2.0 1.5 2.2Verona 2.1 1.8 2.3

1063
The 10-year follow-up study conducted by Merikangas and 
Angst(22) revealed that approximately 50 per cent of patients 
continued to exhibit symptoms. The WHO study(23) reported that 
patients with a diagnosis of neurasthenia had, on average, been disabled for 8 to 7 days during the month preceding the examina-tion. Hickie et al .
(25) conﬁ  rmed the chronicity of the condition. 
They reported that 80 per cent of people who met the ICD-10 criteria in the past 12 months were also current cases.
In the Australian study Hickie et al.(25) showed that there was more 
comorbidity with major depression, panic disorder, and general-ized anxiety disorder than could be expected by chance after adjust-ment for the prevalence of the comorbid disorder and the average level of comorbidity of that disorder.
Treatment

Treatment
Although there are reports that antidepressants can be effective these are not supported by published data on randomized double-blind controlled trials. Indeed, no such trials have been carried out on any form of psychiatric treatment for neurasthenia. In the absence of such data the clinician will have to rely on the adage of ‘When not able to do any good, avoid doing any harm’ . Thus aggres-sive treatment and investigations should be avoided. Patients are best managed in a supportive relationship with due regard given to their psychological and psychosocial needs.
General and non-speciﬁ  c strategies may also be used. These can 
include regular graded increase in exercise, promotion of sleep hygiene, cognitive techniques to break the cycle of symptoms lead-ing to decreased activities, and improving social support.
Clinicians working in an environment where people with mental 
illnesses are stigmatized might ﬁ  nd it easier to accede to social

illnesses are stigmatized might ﬁ  nd it easier to accede to social 
demands. Clinicians work at two levels in these situations. At one level he or she will have made a diagnosis of a psychiatric disorder and have prescribed the appropriate treatment. At another level the practitioner will be using neurasthenia as a euphemism for mental illness. Therefore, until stigmatization can be reduced or abolished, this unenviable state of affairs will continue.
Complementary medicine
The extracts of leaves from the Ginkgo biloba  tree contain ginkgo-
 flavone glycosides and trepenoids. Ginkgo  is widely used as a
cognitive enhancer. The roots of the Panax ginseng  contain several 
triterpine glycosides, which are believed to have physical performance enhancing properties. This root is used in traditional Chinese  medicine to treat a large variety of diseases including neurasthenia. Wesnes et al .

(26) evaluated the effects of a Ginkgo biloba/ginseng
 combination on 64 healthy volunteers who fulﬁ  lled the ICD-10 crite-
ria for neurasthenia. This was a 90-day, double-blind, placebo- controlled, parallel group study. They reported that the combined dose of 120 mg Ginkgo  extract and 300 mg of ginseng  extract was 
 signiﬁ  cantly better than placebo in reducing the symptoms of neuras-
thenia by day 90. Adverse effects were nausea and abdominal pain.
The mushroom, Ganoderma lucidum , known as lingzhi in China 
has been widely used to treat cancer, diabetes, and neurasthenia. It is the only known source of ganoderic acid, which has a molecular 
structure similar to steroid hormones and is a source of biologi-cally active polysaccharide. Ganoderma  is one of the most highly 
ranked herbal medicines by Asian people. Tang et al.
(27) conducted 
a randomized, double-blind, placebo-controlled parallel study to investigate its efﬁ  cacy and safety in the treatment of Chinese

a randomized, double-blind, placebo-controlled parallel study to investigate its efﬁ  cacy and safety in the treatment of Chinese 
patients who fulﬁ  lled the ICD-10 diagnostic criteria for neurasthe-
nia. Their ﬁ  ndings indicated that Ganoderma  was signiﬁ  cantly 
superior to placebo with respect to the clinical improvement of symptoms in neurasthenic. Adverse effects were mild consisting of nausea, dry mouth, and vomiting.
Complementary medicine is increasingly being used either as an 
alternative or in addition to conventional psychotropic medica-tions. Refer to Chapter 6.2.9 for further information.

As to whether neurasthenia will be replaced by chronic fatigue syndrome (Chapter 5.2.7) or subsumed under somatoform disorders (Chapter 5.2.1), and thus be relegated to a footnote in the history of medicine, or will enjoy resurgence with a new set diag-nostic criteria will be determined by future research and clinical data.
Starcevic, V . (1999). Neurasthenia: cross-cultural and conceptual issues in 
relation to chronic fatigue syndrome. General Hospital Psychiatry ,
21, 249–55.
Tang, W., Gao, Y., Chen, G., et al. (2005). A randomized, double-blind 
and placebo-controlled study of a Ganoderma lucidum
polysaccharide extract in neurasthenia. Journal of Medicinal Food ,
8, 53–8.
Web pages: www.kosmix.com/health Type in neurasthenia to search

8, 53–8.
1. Beard, G.M. (1869). Neurasthenia or nervous exhaustion. Boston Medical 
and Surgical Journal ,3, 217–20.
2. Beard, G. (1881). American nervousness: its causes and consequences .
Putnam, New Y ork.
3. Freud, S. (1895). On the grounds for detaching a particular syndrome 
from neurasthenia under the description of ‘anxiety neurosis’ . In Standard edition of the complete psychological works of Sigmund Freud ,
Vol. 1 (ed. J. Strachey), p. 139. Hogarth Press, London.
4. Freud, S. (1895). Obsessions and phobias: their psychical mechanism 
and their etiology. In Standard edition of the complete psychological works 
of Sigmund Freud , Vol. 3 (ed. J. Strachey), pp. 74–82. Hogarth Press, 
London.
5. Kraepelin, E. (1902). Clinical psychiatry  (trans. A.R. Defendorf), 
pp. 96–104. Macmillan, New Y ork.

London.
6. Lin, T.S. (1989). Neurasthenia revisited: its place in modern psychiatry. 
Culture, Medicine and Psychiatry ,13, 105–29.
7. Lin, T.S. (1985). The shaping of Chinese psychiatry in the context of 
politics and public health. In Mental health planning for one billion 
people  (eds. T.S. Lin and L. Eisenberg), pp. 13–14. University of British 
Columbia Press, Vancouver.
8. Li, C.P . and Zhang, W.H. (1985). Neurasthenia. In Psychiatry
(ed. Y.C. Shen), pp. 407–12. People’s Health Press, Beijing (in Chinese).
9. Kleinman, E.A. (1982). Neurasthenia and depression: a study of 
somatization and culture in China. Culture, Medicine and Psychiatry ,
6, 117–90.5.2.10  neurasthenia

SECTION 5  psychiatry and medicine 1064
10. Rin, H. and Huang, M.G. (1989). Neurasthenia as a nosological 
dilemma. Culture, Medicine and Psychiatry ,13, 215–26.
11. Cheung, F. (1989). The indigenization of neurasthenia in Hong Kong. 
Culture, Medicine and Psychiatry ,13, 227–41.
12. Suzuki, T. (1989). The concept of neurasthenia and its treatment in 
Japan. Culture, Medicine and Psychiatry ,13, 203–13.
13. Morita, M., Kondo, A. and LeVine, P . (1998). Morita therapy and the 
true nature of anxiety-based disorders (Shinkeishitsu) translated by Kondo, A. pp. 55–62. SUNY Press, New Y ork..
14. Paterson, G.O. (1969). The economics of illness: an employee sickness 
study. The Medical Journal of Australia ,2, 249–52.
15. Drinka, G.F. (1984). The birth of neurosis: myth, malady and the 
Victorians . Simon and Schuster, New Y ork.
16. Osler, W. (1900). The principles and practice of medicine  (7th edn), 
pp. 166–7. Appleton, New Y ork.

17. Sims, M. (1968). Guide to psychiatry , p. 444. Livingstone, Edinburgh.
18. Chatel, J.C. and Peele, R. (1970). A centennial review of neurasthenia. 
The American Journal of Psychiatry ,126, 1404–13.
19. World Health Organization. (1992). The ICD–10 classiﬁ  cation of mental 
and behavioural disorders: clinical descriptions and diagnostic guidelines .
20. Chinese Psychiatric Society. (2001). The Chinese classiﬁ  cation of mental 
disorders  (CCMD-3 ). Shandong Publishing House of Science and 
T echnology, Shandong (in English and Chinese).21. Lee, S. (1996). Cultures in psychiatric nosology: the CCMD–2–R and 
the International classiﬁ  cation of mental disorders. Culture, Medicine 
and Psychiatry ,20, 421–73.
22. Merikangas, K. and Angst, J. (1994). Neurasthenia in a

22. Merikangas, K. and Angst, J. (1994). Neurasthenia in a 
longitudinal cohort study of young adults. Psychological Medicine ,
24, 1013–24.
23. Üstün, T.B. and Sartorius, N. (1995). Mental illness in general health 
care: an international study . Wiley, Chichester.
24. Zhang, W.X., Shen, Y.C., and Li, S.R. (1998). Epidemiological 
investigations on mental disorders in 7 areas of China. Chinese Journal 
of Psychiatry ,31, 69–71.
25. Hickie, I., Davenport, I., Issakidis, C., et al. (2002). 
Neurasthenia: prevalence, disability and health care characteristics 
in the Australian community. The British Journal of Psychiatry ,
181, 56–61.
26. Wesnes, K.A., Faleni, R.A., Hefting, N.R., et al. (1997). The subjective, 
cognitive and physical effects of a Ginkgo biloba /Panax ginseng
combination in healthy volunteers with neurasthenic complaints. Psychopharmacology Bulletin ,33, 677–83.

27. Tang, W., Gao, Y., Chen, G., 
et al. (2005). A randomized, double-blind 
and placebo-controlled study of a Ganoderma lucidum  polysaccharide 
extract in neurasthenia. Journal of Medicinal Food ,8, 53–8.

Medical and surgical conditions 
and treatments associated with psychiatric disorders5.3
 5.3.1 Adjustment to illness and handicap
 5.3.2 Psychiatric aspects of neurological disease
 5.3.3 Epilepsy
 5.3.4 Medical conditions associated 
with psychiatric disorder
 5.3.5 Psychiatric aspects of infections
José Luis Ayuso-Mateos
 5.3.6 Psychiatric aspects of surgery (including transplantation)
 5.3.7 Psychiatric aspects of cancer
 5.3.8 Psychiatric aspects of accidents, burns, and other physical trauma
5.3.1 Adjustment to 
illness and handicap
Not everybody who develops a serious physical illness will have

Not everybody who develops a serious physical illness will have 
psychiatric problems as a consequence. T o understand why, it is useful to have a model of the normal process of adjustment to stress; psychiatric disorder can then be seen as arising when that process, often called coping, is either maladaptive or is adaptive but only partially successful. This chapter will start with an outline of one theory of stress and coping as it applies to physical illness, 
followed by a review of disorders of adjustment to illness. A dis-tinction will be drawn between recent-onset illness, which provokes an acute response, and long-standing illness, where the challenge is more often to adjust to chronic disability.
Adjustment to illness and handicap

A number of diseases are reviewed in later chapters, and therefore this chapter will deal with general principles. For more details on particular diseases, the reader should consult specialist textbooks of psychiatry or health psychology.
Illness as a stress
Stress is a word that is used in different ways. Sometimes it refers to an environmental stimulus—a threat or demand from the out-side world. This deﬁ  nition lies behind various measures, such as 
the Social Readjustment Rating Scale
(1) or the Bedford College 
Life Events and Difﬁ  culties Schedule(2) which characterize life 
experiences and produce standardized measures of their severity. According to this view, experiences have properties—as losses, or challenges, or dilemmas—that can be identiﬁ  ed by knowing some-
thing of the social circumstances of the subject of those experiences but without knowing about the meaning given to them by the person experiencing them.

Another meaning of stress is that it is a bodily state, so that events 
are only regarded as stressful if they produce changes in the individ ual. 
The best-known example of this usage comes from physiology.
(3)
Stress as a psychological state is also a common lay meaning; when people describe themselves as ‘stressed’ they are usually referring to a state of tension or autonomic arousal.
Y et another way to understand stress, which is useful in consider-
ing physical illness, is that it arises out of an interaction between environmental demands and the resources available to deal with them. This view is articulated in the transactional model of Lazarus and Folkman.
(4) According to the theory, when faced with a new

(4) According to the theory, when faced with a new 
experience individuals assesses its likely impact (the primary appraisal) and assess their resources (the secondary appraisal). Stress arises when this double appraisal identiﬁ  es a mismatch 
between demands and resources that cannot be narrowed by cop-ing manoeuvres.

SECTION 5  psychiatry and medicine 1066
(a) Illness as a demand or threat (the primary appraisal)
There are a number of characteristics of an experience that 
increase the chances of it being appraised as threatening. These include immediacy, ambiguity, uncontrollability, or undesirability. The probability that many people will share an interpretation of a particular episode explains the similarity of people’s responses to certain illnesses. The possibility of individual, even idiosyncratic, interpretations can explain sharp differences between people with apparently the same disorder.
A useful way to construe individual appraisals of illness is 
outlined by Leventhal et al .
(5) in their theory of internal illness 
representations. The common elements of the illness representa-tion can be identiﬁ  ed from a simple self-report questionnaire
(6).
Illness beliefs cannot be assumed solely on the basis of the illness 
from which a person is suffering, or from his or her social context.(7)

(6).
Individuals may hold unpredictable beliefs—that an illness is inherited from a family member, or that it is a punishment for a misdemeanour, or that it may be curable by adopting an unusual diet. For some, the representation of illness overlaps with the repre-sentation of self, so that sufferers see themselves as living their illness rather than suffering from it.
(8)(see Box 5.3.1.1)
The characteristics of a particular disease are not the only com-

ponent of the illness that can make it threatening. Illness occurs in a social and interpersonal context, and while the responses of other people may be helpful, they may in some cases contribute to the demands of the situation. For example, a partner may withdraw or become depressed, or family members may become intrusive or overcontrolling. Being ill confers a special status, the so-called sick role, but it is a status acquired at a cost in the loss of indepen-dence and certain rights. While disability may arise largely from the impairments caused by a disease, much handicap is socially determined.
(b) Resources for responding to illness (the secondary
  appraisal)
The focus of secondary appraisal is twofold: the person’s personal 
resources, and the resources external to them, mainly in the imme-diate social network.
Personal resources may be deﬁ  ned in a number of ways, for

Personal resources may be deﬁ  ned in a number of ways, for 
example cognitive attributes, personal characteristics, or personal-ity traits.
The other resource for the individual is social support. There are 
many approaches to understanding support, but a useful one
(9) is 
to regard it as having four components:
1 emotional support, conveying a sense of being cared about 
or loved
2 esteem support, conveying a sense of being valued or respected
3 instrumental support, conveying practical help4 informational support, conveying knowledge relevant to tackling 
the problem
The family’s reaction to illness has an important impact on the type

The family’s reaction to illness has an important impact on the type 
of support available. If they are rejecting, intolerant of dependence, or unsympathetic to the needs of the patient—for example, to change their diet, or stop smoking, or take more (or less) exercise—then they may offer too little support. On the other hand, they may be overprotective, refusing to allow the patient a reasonable degree of autonomy and discouraging active coping. Sometimes, members of a family will hold different views about the nature of an illness, 
leading to conﬂ  ict, which is not always revealed to doctors. More

leading to conﬂ  ict, which is not always revealed to doctors. More 
often, they share views. If such views are inaccurate (so-called fam-ily myths) and yet strongly held, then they can be a powerful barrier to the patient accepting medical advice. It is a common observation that patients with chronic illness who are depressed often have a carer who is depressed, and this tendency to share (often dysfunc-tional) beliefs and coping styles is one reason for that.
(c) Coping with illness
Coping refers to efforts to reduce the gap between demands and resources. Coping is described according to its aims, the techniques used to achieve those aims, and according to the overall coping style adopted.
The aims  of coping are either problem focused, designed to mod-
ify the demands of the situation, or emotion focused, designed to modify how one feels about a situation.
(4) Emotion focused coping

(4) Emotion focused coping 
generally works well but only transiently. It is best reserved for brief stresses, such as unpleasant medical procedures, or for situations in which nothing can realistically be done to modify the stress.
The techniques  for coping serve to mobilize available resources. 
Vocabularies differ for describing them. Cognitive coping tech-niques include information seeking, downplaying, or adopting a deﬁ  ant or overoptimistic attitude. In psychodynamic terms, the

Vocabularies differ for describing them. Cognitive coping tech-niques include information seeking, downplaying, or adopting a deﬁ  ant or overoptimistic attitude. In psychodynamic terms, the 
two most commonly used techniques are probably denial and regression. In common usage, the techniques referred to by these vocabularies overlap. Behavioural coping may involve changing ones lifestyle, such as exercising more or excessive drinking of alcohol. Social coping is a particular form of behavioural coping, and may involve increasing contacts or accepting help from pro-
fessional agencies. In chronic illness, successful coping may be 
accompanied by a slower process of reappraisal—in which the patient comes to a different understanding of the illness, from that apparent at initial diagnosis—through for example beneﬁ  t-ﬁ nding
and downward comparison  (with others who have worse disability, 
pain, or whatever).
Coping styles  are more general approaches to coping. Two

Coping styles  are more general approaches to coping. Two 
contrasted styles are active/engaged (sometimes called ‘approach’) coping and passive/disengaged (sometimes called ‘avoid’) coping.
(10)
While it is appealing to characterize people as having a particular coping style, and while it is possible to think of typical examples from personal experience, in fact most people do not have a sufﬁ  -
ciently unchangeable repertoire of coping techniques to merit the label of a style.
(a) Deﬁ  nition and classiﬁ  cation
The emphasis in ICD-10(11) is on emotional disturbance as the 
characteristic feature of adjustment disorders—some disturbance of behaviour is acknowledged, particularly in adolescence. Box 5.3.1.1 Components of the illness representation
◆ identity (label and associated symptoms)
◆ causal ideas
◆ consequences (severity and likely impact)
◆ time-line (natural history)

◆ curability or controllability

1067
However, it is common to encounter cognitive or behavioural 
changes that interfere with social functioning and quality of life, and yet which are not attributable to the consequences of mood disorder. DSM-IV
(12) acknowledges this possibility more directly, 
including a category of ‘Adjustment disorder, unspeciﬁ  ed’ , which 
covers ‘maladaptive reactions (e.g. physical complaints, social with-drawal, or work or academic inhibition)’ .
Examples of cognitive problems are extreme helplessness, denial 
of the existence of illness, or of the handicap associated with it. Behavioural problems may include marked social withdrawal or lack of self-care, or irrational non-adherence to treatment. Emotional problems are typically thought of as anxiety or depression, but irritability is also common.
(b) Diagnosis and differential diagnosis
The diagnostic features of adjustment disorders are relatively non-speciﬁ  c, comprising mood symptoms and behaviour disturbances,

The diagnostic features of adjustment disorders are relatively non-speciﬁ  c, comprising mood symptoms and behaviour disturbances, 
which do not meet the criteria for a diagnosis of another disorder, and yet which are sufﬁ  cient to amount to a mental disorder. The 
two main diagnostic questions are as follows.
◆ Does the patient have a diagnosable mental disorder?
◆ If there is a mental disorder, should it be given another more 
speciﬁ  c label than ‘adjustment disorder’?
What distinguishes normal adjustment from a disorder? The ﬁ  rst 
criterion is whether the symptoms are persisting beyond the time when they might be attributable to the stressor. This judgement is relatively straightforward when the stressor is a single event. However, if illness is more persistent or intermittent—such as cancer followed by intensive treatment, or multiple sclerosis—then it is less easy to judge.

The second criterion is whether the response is causing avoidable 
social dysfunction. For example, in many cultures illness is followed by a period of convalescence, during which activity is reduced and a return to full social responsibilities is deferred. This may be a healthy avoidance of activity, if it allows full recovery from illness, but prolonged avoidance of activity may lead to secondary physical problems as well as social isolation and loss of role.
When adjustment disorders are associated with chronic illness 
and handicap, the duration criterion cannot apply. An individual 
may present symptoms because his or her response is outside the 
culturally acceptable range; for example, he or she may be too 
demanding or uncooperative, or too passive and dependent. It is 
unwise to regard a presentation as disordered simply on these 
grounds. The best indicator is whether the individual is achieving

grounds. The best indicator is whether the individual is achieving 
the highest level of function and the lowest level of distress of which they are capable under the circumstances. This means that each person must be diagnosed according to his or her own context, and that a standardized set of criteria cannot be applied.
The differentiation of adjustment disorders from other psychiat-
ric disorders is more straightforward, and depends on the presence or absence of key symptoms. The main conditions found in asso-ciation with physical illness are depressive disorders, anxiety disor-
ders, and occasionally post-traumatic stress disorder.
Little is known about the epidemiology of adjustment disorders

Little is known about the epidemiology of adjustment disorders 
other than those involving mood disturbance, because of the absence of standardized diagnostic criteria.Psychiatric symptoms are distributed in the general population,

with a positive skew to the distribution. In the physically ill, the same pattern of distribution is seen, but the curve is shifted to the right. The increase in psychiatric symptoms is contributed to by a general increase in all the common symptoms. The usual way to identify cases is to select those who cross an accepted threshold for symptom levels—as determined, for example, by one of the standardized self-report questionnaires—and then to apply diag-nostic criteria. Adopting this approach, rates of diagnosable mood disorder among the physically ill are about double what they are in the general population. That is, 30 to 50 per cent (depending on the population studied and the diagnostic criteria employed) of the physically ill have a mental disorder. Approximately two-thirds of these cases are adjustment disorders, the rest meeting criteria for another disorder (usually depressive).
The elderly report lower rates of psychiatric disturbance. This

The elderly report lower rates of psychiatric disturbance. This 
may be a cultural effect, with the elderly disposed to report fewer symptoms of distress as a result of stoicism learned through experience of adversity earlier in life. Alternatively, the elderly may genuinely respond differently to physical illness.
Mood symptoms and adjustment disorders are commoner in 
response to acute illness than they are in chronic illness.
(d) Aetiology
There are several reasons why coping might fail.
First, demands may be overwhelming. The news that one has a 
terminal illness takes time to assimilate—to understand all its meanings, grasp all the threats and losses involved. While that pro-cess of appraisal is going on, it is difﬁ  cult to marshal resources and 
use them effectively. This explains, in part, why mood disorder is more commonly associated with acute than chronic illness.
Second, resources may be inadequate or missing. One problem

Second, resources may be inadequate or missing. One problem 
associated with physical illness is that it may impair personal resources as a primary effect of the disease process—most impor-tantly when the illness has effects on the central nervous system by virtue of the direct involvement of the brain or through the neuro-logical effects of systemic disturbance.
Third, coping responses may be ineffective. There are few rules 
about what makes effective coping. In general, a broad and ﬂ  exible 
repertoire is desirable, with a strong element of active problem-focused techniques. However not all illnesses, nor all aspects of a

repertoire is desirable, with a strong element of active problem-focused techniques. However not all illnesses, nor all aspects of a 
particular illness, are likely to be amenable to problem-focused coping. Probably the most effective coping is matched to the situa-tion. That is, the coping matches the demands, so that heavy reli-ance is not placed on problem-focused coping when little in the situation can change, nor excessive use made of emotion-focused coping when active involvement in illness management is needed.
A common problem of failure to match coping to the situation is

A common problem of failure to match coping to the situation is 
found in patients with chronic illness, who are responding to their circumstances as if they none the less have an acute illness. In acute illness, problem-focused coping often involves seeking reversal or even cure of the illness process, while emotion-focused coping involves dealing with the anxiety of uncertainty, or grieving if the prognosis is clearly poor. On the other hand, in chronic illness, problem-focused coping involves symptom management and maximizing function, while emotion-focused coping requires a degree of acceptance.
It is not easy to predict who will develop an adjustment disorder. 
Certainly the risk is not strongly linked to physical diagnosis, or 5.3.1 adjustment to illness and handicap

SECTION 5  psychiatry and medicine 1068
within a particular diagnostic group to physical disability. The most 
robust ﬁ  nding is that a previous history of psychiatric problems 
increases the risk of psychiatric problems associated with physical illness.
By deﬁ  nition, adjustment disorders arise shortly after diagnosis. 
In practice, there is variation; some people respond immediately and develop symptoms within days, while others develop symp-toms weeks or even months after diagnosis. The losses associated with illness may only become apparent when a person leaves hospi-tal and faces functional impairment at home. Carers and others in the social network respond differently to acute and chronic illness, and it may take time for that to become clear. The greater the delay from the onset of illness to the emergence of symptoms, the harder it is to make a diagnosis of adjustment disorder. In clinical practice, it is reasonable to set an upper limit of a year.

Most adjustment disorders provoked by a newly onset illness, 
resolve within weeks. Slower recovery takes place over 12 or 18 months. If recovery has not occurred by then, the patient has usually developed another mental disorder, such as a depressive 
disorder. Accurate data are few, but probably no more than 10 per cent 
of patients develop a prolonged adjustment disorder.
The psychiatric symptoms of adjustment disorder impair quality 
of life, so much so that all standardized quality-of-life measures include mood symptoms in their proﬁ  le. Psychiatric morbidity 
associated with physical illness is also a risk factor for self-harm and for completed suicide. Adjustment disorders are likely to have an effect on the outcomes of treatment for physical disease.
(13)

(13)
Health service costs are greater for patients with physical illness and psychiatric co-morbidity; lengths of stay are longer for hospi-tal inpatients; the functional outcomes of rehabilitation may be poorer, and there is some evidence that there may also be an increased mortality. The mechanism for these effects may be broadly behavioural or physiological. Examples of the former are increased rates of smoking, lack of exercise, and poor adherence to treatment regimes among people with mental disorders. Examples of the latter include activation of the hypothalamic–pituitary–adrenal axis or increased cytokine production associated with chronic emotional disorder.
(i) Drug treatments
Antidepressants can be effective in the presence of ph ysical illness.(14)
There is no good evidence to support claims for a great superiority 
in efﬁ  cacy of serotonin-reuptake inhibitors. Although their long-

term tolerability may be greater than older drugs in patients with physical disease, they are not without toxicity—for example they have been associated with increased falls and gastrointestinal haem-orrhage. Tricyclic antidepressants have advantages in treating patients with insomnia or chronic pain. Cost differences are substantial.
(ii) Psychological treatments
A number of brief psychological therapies have been shown to be effective in treating depression; namely cognitive-behaviour therapy, problem-solving therapy, interpersonal therapy, and brief dynamic therapy. Such therapies may also be effective in treating adjustment disorder in the physically ill,
(15,16) although they may have disap-
pointingly weak effects upon physical outcomes. Therapy may need to be modiﬁ  ed to allow for fatigue or concentration problems, and

pointingly weak effects upon physical outcomes. Therapy may need to be modiﬁ  ed to allow for fatigue or concentration problems, and 
sessions need to be arranged ﬂ  exibly to accommodate hospital 
appointments and other treatment needs.
(g) Management
(i) Identifying cases
A major difﬁ  culty in delivering treatment to people with adjust-
ment disorders is the difﬁ  culty in identifying cases. There are 
several self-report questionnaires, which may be used to screen for patients with mood disorder. In certain settings such question-naires can be delivered routinely to all patients, for example by means of computers with touch screen technology, and they are useful for alerting staff to the presence of mood symptoms—but their positive predictive value is too low to allow for accurate use in identifying those who need referral to specialist services. Their use is also difﬁ  cult to integrate into routine clinical practice, and

response rates outside research studies are usually low.
(17) Their 
use is best restricted to specialist services where the clinical staff are clear about what response they will make to a high score, since this is where there is some evidence for the beneﬁ  ts of case-ﬁ  nding. 
There are no useful standardized instruments for the detection of other problems with adjustment.
Instead, clinicians should be encouraged to consider the possibility 
of psychiatric disorder when there is a gap between impairment and handicap so that the patient is doing worse in rehabilitation than the severity of their disease would suggest they should be, when there are multiple complaints that are difﬁ  cult to explain, or 
when multiple drug treatments are being administered without conspicuous beneﬁ  t. The clinical interview is the mainstay of 
diagnosis.
There are a number of common reasons for failing to recognize

There are a number of common reasons for failing to recognize 
adjustment disorders. First, the questions simply are not asked, or attempts by the patient to introduce the topic of psychological problems are blocked or sidestepped. Second, questions may be asked, but in circumstances where it is difﬁ  cult for the patient to 
answer honestly—when there is no privacy, or the person asking is 
obviously too busy to listen to any but a conventional answer. Third, expressions of distress may be normalized, and thus dis-missed: ‘Of course it’s natural you will feel like that’ means to the patient ‘So please don’t mention it again’ .
(ii) Broadening the repertoire of psychological responses
No single intervention is going to be effective for all patients with psychological problems arising from difﬁ  culties with adjustment to

No single intervention is going to be effective for all patients with psychological problems arising from difﬁ  culties with adjustment to 
illness. Realistic management therefore involves offering what has been called a ‘menu of interventions’ .
(18) A currently favoured 
model is a so-called stepped care  model in which intervention is 
organized in a hierarchy according to intensity of treatment and the expertize needed to deliver it e.g. see Box 5.3.1.2. While unfo-cused ‘support’ is of limited value (because it does not encourage active secondary appraisal and experiments with different coping strategies) there are now many brief and ﬂ  exible psychological 
therapies available, some of which may be deliverable by staff in the primary care or physical healthcare service (see Box 5.3.1.3). In col-
laborative care  such ﬁ  rst line psychological treatments, along with

laborative care  such ﬁ  rst line psychological treatments, along with 
medication management and simple social care, are delivered by non-mental health staff and monitored by a case manager, with a mental health professional providing supervision and back-up consultation. Successful trials have been conducted in (for  example) heat disease
(19) and diabetes.(20)

1069
For more severe or persistent problems, referral to specialist 
services is appropriate—ideally liaison services that operate in the primary or secondary care settings where patients receive their main care. Psychiatric treatment of the physically ill, especially in 
hospital, requires a number of modiﬁ  cations to routine clinical 
practice, which are sometimes overlooked.
First, an extra effort has to be made to meet the family and car-
ers. They may be reluctant to attend if there is hostility in the fam-ily, or if missed time from work is creating ﬁ  nancial pressures, but 
failure to interview others makes it near impossible to come to a full and accurate formulation of the problem.
Second, personal contact with the referrer is highly desirable. 
The ‘real’ question may not be that posed in the referral, and can only be identiﬁ  ed by probing. Advice is much more likely to be

The ‘real’ question may not be that posed in the referral, and can only be identiﬁ  ed by probing. Advice is much more likely to be 
followed if it is delivered face to face, and followed up with a later visit to check on compliance! This direct contact with non-psychiatric colleagues is one of the deﬁ  ning characteristics of liaison psychiatry, 
and its importance cannot be overemphasized.
Third, it must be recognized that the course of psychiatric treat-
ment needs to be modiﬁ  ed. Appointments will be missed, or inter-
rupted, by the demands of physical treatment. And psychological issues may well not be resolved by a single clinical encounter; a relapse of illness may provoke a further episode with new features, and patients often have to return repeatedly to work through themes 
in therapy, as they are re-challenged with new physical problems.
(h) Prevention

There are two broad approaches to prevention, namely education and support.
Education and the provision of information and advice about the 
illness and its management is desirable as an informed patient is more likely to be an effective partner in treatment, and because it is popular with patients. Disappointingly, however, it is not an effective means of preventing psychiatric problems. This is probably because, while it facilitates primary appraisal, it does nothing to facilitate sec-ondary appraisal or the use of effective coping strategies.
Provision of support is also popular. It takes a number of forms, 
including self-help groups, volunteer visiting, and professional sup-port workers—usually with knowledge of a particular disease such as AIDS or a stroke. Again, there is little evidence that it prevents psychiatric problems. Perhaps this is because it usually provides

emotional support; which in itself may be worthwhile but which is 
insufﬁ  cient if not combined with a more problem-focused approach.
In conclusion, there are no clear indications that we can prevent 
the development of adjustment disorders. The mainstay of current management is therefore to identify existing cases and to offer specialist care to those who are most symptomatic or handicapped, and to those who are not improving spontaneously.
Adjustment to terminal illness: care of 
the dying
Adjustment to terminal illness has much in common with adjust-
ment to other severe illness, and is not speciﬁ  cally the province of 
psychiatrists. For a detailed discussion of the care of the dying, the reader is referred to a more specialized text.
(22) Here we will discuss 
two issues that are commonly presented to the psychiatrist in this setting: the diagnosis of depression and other adjustment disorders, and the issue of suicide.Box 5.3.1.3 Brief psychological treatment of use in the

medically ill
◆Motivational interviewing  is an approach developed to 
encourage people to attempt change in addictive behaviours. It may be useful in engaging people in demanding treatments, or in improving adherence to treatment regimes.
◆Graded activity  has been used to treat negative symptoms in 
mental illness like schizophrenia or depressive disorder. It is 
effective in improving function in chronic fatigue syndrome, 
and is worth using in other conditions where inactivity and passivity is out of proportion to physical disability.
◆Anger management  is a modiﬁ  cation of cognitive-behaviour 
therapy, which may be useful where irritability or aggressive behaviour is complicating adjustment.
◆Interpersonal therapy(21) was initially developed for the treat-
ment of depression, but it has obvious applications in the ﬁ  eld of

ment of depression, but it has obvious applications in the ﬁ  eld of 
physical illness. In the terminology of interpersonal therapy, illness represents a role transition, and the focus in therapy is therefore on negotiating that transition with key others in the patient’s life.
◆Family therapy and couples therapy  are rarely considered (or 
available) for adults with physical illness, and yet many of the external resources needed for coping are in the family.5.3.1 adjustment to illness and handicap
Box 5.3.1.2 Stepped care in the treatment of depression (NICE 
clinical guideline 2004)
Who is 
responsible for care?What is the
focus?What do they do?
Step 5 Inpatient care, 
crisis teamsRisk to life, severe 
neglectMedication, 
combined treatments, ECT
Step 4 Mental health 
specialistsincluding crisis teamsTreatment-
resistant, recurrent, atypical and psychotic depression, and those at signiﬁ  cant riskMedication,

resistant, recurrent, atypical and psychotic depression, and those at signiﬁ  cant riskMedication, 
complex psychological interventions, combined treatments
Step 3 Primary care 
team, primary care mental 
health workerModerate or 
severe depressionMedication, 
psychological interventions, social support
Step 2 Primary care 
team, primary care mental health workerMild depression Watchful waiting, 
guided self-help, computerized CBT, exercise brief psychological interventions
Step 1 GP , practice 
nurseRecognition Assessment
National Institute for Health and Clinical Excellence (NICE) (2005). CG22 Anxiety: quick 
reference guide. London: NICE. Available from http://www.nice.org.uk/nicemedia/pdf/CGO22quickrefguideamended.pdf. Reproduced with permission.

SECTION 5  psychiatry and medicine 1070
Diagnosis of depression and adjustment disorders 
in the terminally ill
As with physical illness, somatic complaints are common in the 
dying and thus, individually, lose their diagnostic or predictive usefulness in the major depressive syndrome. Even psychologically, a degree of hopelessness may be appropriate. Anxiety is a common symptom in the dying, but it is not necessarily pathological. Like depression, it may result from physical disability, uncontrolled pain, or pre-existing anxiety disorders. In these circumstances a more detailed examination of the attitudes of the patient is necessary. Pervasive global hopelessness, feelings that life has had no meaning, strong feelings of guilt or punishment, and suicidal thoughts are pointers towards depressive illness in the terminally ill.
Assessing suicidal thoughts in the terminally ill

Several studies have shown that the prevalence of suicidal thoughts among patients with terminal cancer is less than 10 per cent.
(23)
However, this contradicts the clinical impression that most patients admit to either suicidal thoughts or thoughts of assisted suicide as an escape from the imaged consequences of losing control. In some patients, having a belief in a ‘way out’ can be positive in offering a sense of control.
Completed suicide is an important complication in patients 
with a terminal illness. General predictors of suicide apply, with the addition of severity of functional impairment, isolation, and delirium. The two most important factors to watch out for are uncontrolled pain and depression. These two factors greatly increase suicide risk but are nevertheless treatable in the terminal 
illness setting.
(24)
People who express a desire to die are nearly always ambivalent.

(24)
People who express a desire to die are nearly always ambivalent. 
The expression of suicidal ideas should never be accepted as rational without a searching enquiry for evidence of subtle external pressures, fear of terminal symptoms or of being a burden on others, and treatable depression.
Pharmacological management of psychiatric disorders 
in the dying
Alleviation of distress rather than cure is the guiding principle of 
the management of the terminally ill. Caution is needed in the selection and prescription of psychotropic drugs.
Anxiolytic medication is usually well tolerated and the concern 
over dependence and tolerance is less of an issue. T erminal metab-olite benzodiazepines, such as lorazepam and oxazapam, can provide symptomatic relief for a variety of conditions even in patients with hepatic impairment. Occasionally, opiates are used in this role where ﬁ  rst-line treatments are unsuccessful.

Antidepressant use in the dying may be more problematic due to 
the adverse effects of sedation, seizures, hypotension, and constipa-tion and urinary retention. For this reason, the choice of drug needs to be individually tailored. Dosage has to be carefully adjusted, beginning at low doses and increasing gradually. The use 
of psychostimulants (dextroamphetamine, methylphenidate) is worth considering. These drugs are used infrequently in general 
psychiatry because of the risks of dependence, but in the terminally ill they may have advantageous ‘energizing’ properties, including increased energy, improved concentration, increased appetite, and possibly, a faster onset of action.Further information
Sharpe, L. and Curran, L. (2006). Understanding the process of adjustment 
to illness. Social Science & Medicine ,62, 1153–66.
Fletcher, J., Bower, P ., Gask, L., et al. (2006). Primary care services for 
depression: a guide to best practice care services improvement partnership .

National Institute for mental Health in England, Department of Health, London.
 1. Holmes, T.H. and Rahe, R.H. (1967). The social readjustment rating 
scale. Journal of Psychosomatic Research ,11, 213–18.
 2. Brown, G. and Harris, T. (1978). Social origins of depression . Tavistock 
 3. Selye, H. (1956). The stress of life . McGraw–Hill, New Y ork.
 4. Lazarus, R.S. and Folkman, S. (1984). Stress, appraisal and coping .
 5. Leventhal, H., Nerenz, D., and Steele, D. (1984). Illness representations 
and coping with health threats. In Handbook of psychology and health
(4th edn) (eds. A. Baum, S.E. Taylor, and J.E. Singer), pp. 219–52. Erlbaum, Hillsdale, NJ.
 6. Weinman, J., Petrie, K., Moss–Morris, R., et al. (1996). The illness

 6. Weinman, J., Petrie, K., Moss–Morris, R., et al. (1996). The illness 
perception questionnaire: a new method for assessing the cognitive 
representations of illness. Psychology and Health ,11, 431–45.
 7. Petrie, K. and Weinman, J. (eds.) (1997). Perceptions of health and 
illness . Harwood, Amsterdam.
 8. Kleinman, A. (1988). The illness narratives: suffering, healing and the 
human condition . Basic Books, New Y ork.
 9. Cohen, S. and Wills, T.A. (1985). Stress, social support and the 
buffering hypothesis. Psychological Bulletin ,98, 310–57.
10. Carver, C.S., Weintraub, J.K., and Scheier, M.F. (1989). Assessing coping 
strategies: a theoretically based approach. Journal of Personality and 
Social Psychology ,56, 267–83.

12. American Psychiatric Association. (1994). Diagnostic and statistical 
13. Saravay, S.M. and Lavin, M. (1994). Psychiatric comorbidity and length 
of stay in the general hospital–a critical review of outcome studies. Psychosomatics ,35, 233–52.
14. Gill, D. and Hatcher, S. (2000). Antidepressants for depression in 
medical illness. Cochrane Library ,4.
15. MacHale, S. (2002). Managing depression in physical illness. Advances 
in Psychiatric Treatment ,8, 297—305.
16. Winkley, K., Landau, S., Eisler, I., et al. (2006). Psychological 
interventions to improve glycaemic control in patients with Type 
I diabetes: systematic review and meta-analysis of randomized 
controlled trials. British Medical Journal ,333, 65–8.

17. House, A. (1988). Mood disorders in the physically ill: problems 
of deﬁ  nition and measurement. Journal of Psychosomatic Research ,
32, 345–53.
18. Goodheart, C.D. and Lansing, M.H. (1997). Treating people with chronic 
disease: a psychological guide . American Psychological Association, 
19. Schrader, G., Cheok, F., Holdacre, et al. (2003). Effect of psychiatry 
liaison with general practitioners on depression severity in recently hospitalized cardiac patients: a randomized controlled trial. JAMA: The 
Journal of the American Medical Association ,288, 2836–45.
20. Williams, J.W., Katon, W., Lin, E.H.B., et al. (2004). The effectiveness 
of depression care management on diabetes-related outcomes in older patients. Annals of Internal Medicine ,140(12), 1015—24.

21. Klerman, G.L. and Weissman, M.M. (1993). New applications of 
interpersonal psychotherapy . American Psychiatric Press, Washington, DC.

1071
22. Wiener, I., Breitbart, W., and Holland, J. (1996). Psychiatric issues in 
the care of dying patients. In Textbook of consultation–liaison psychiatry
(eds. J.R. Rundell and M.G. Wise), pp. 804–31. American Psychiatric 
23. Brown, J.H., Henteleff, P ., Baratat, S., et al. (1986). Is it normal for 
terminally ill patients to desire death? The American Journal of 
Psychiatry ,143, 208–11.
24. Bolund, C. (1985). Suicide and cancer II: medical and care factors in 
suicide by cancer patients in Sweden. Journal of Psychosocial Oncology ,
3, 17–30.
5.3.2 Psychiatric aspects 
of neurological disease
Psychiatric abnormalities are an integral part of neurological dis-
ease and their study can improve our understanding of the neural basis of psychiatric illness. This chapter deals with common neuro-logical diseases where psychiatric symptoms are prominent.
Stroke
Stroke is deﬁ  ned as the sudden loss of blood supply to an area of

Stroke
Stroke is deﬁ  ned as the sudden loss of blood supply to an area of 
the brain resulting in permanent tissue damage and is the com-monest neurological disorder. The incidence of stroke for those aged between 35 and 65 is between 90 and 330 per 100 000. It is commoner in men and the incidence increases with advancing age. Ischaemic stroke is commoner than haemorrhagic stroke and accounts for 80 to 85 per cent of all cases.
Its prevalence is around 30 per cent in the ﬁ  rst few weeks after a 
stroke—two-thirds of the patients ﬁ  t the criteria for major depres-
sion and the rest for minor depression. Survivors remain at an ele-vated risk for depression for many years.
◆ Diurnal variation of mood, weight loss, anergia, insomnia, and 
loss of libido are prominent in the early stages.
◆ Anhedonia, suicidal ideation, loss of self-esteem, and feelings of 
guilt become evident later.
◆ Irritability and aggressive behaviour are common, especially in

◆ Irritability and aggressive behaviour are common, especially in 
those with cognitive impairment.(1)
◆ The onset of depression may occur acutely in the early post-
stroke period or be delayed for 6 months or more.
(b) Factors associated with post-stroke depression
Early after stroke, anterior left-sided lesions involving the cortex and subcortical regions, especially the basal ganglia, and right posterior lesions are more frequently associated with depression.
(2)
In time these associations become less marked.(3) Cognitive impair-
ment is closely associated with depression early after stroke,(4)
and is present in 70 per cent of those with major and 43 per cent of those with minor depression. Old age, a past or family history of depression, and negative life events in the preceding 6 months 
substantially increase the incidence of post-stroke depression.

Disruption of fronto-subcortical circuits, directly or as a distant 
effect of stroke, plays a central role in the causation of depression. Decreased metabolism in orbitofrontal, anterior cingulate, and inferior temporal regions has been reported using PET .
(5)
Serotonergic mechanisms have been implicated, with a reduction 
of 5-hydroxytryptamine-2 receptor binding in the temporal cortex, especially in left hemisphere stroke.
(c) Course and prognosis
The average duration of major depression is around 1 year, with spontaneous remission in many patients. Symptoms of minor depression may persist for 2 years or more. The presence of depres-sion and other psychiatric diagnosis in the ﬁ  rst 3 years after a stroke 
substantially increases the risk of death after controlling for cardio-vascular and other risk factors.
Anxiety
◆ About a quarter of patients fulﬁ  l criteria for generalized anxiety

Anxiety
◆ About a quarter of patients fulﬁ  l criteria for generalized anxiety 
disorder during the acute post-stroke phase.
◆ Rates are lower in community studies (5 per cent)(6) and 1 or 
2 years after stroke (4 to 18 per cent). Half of those with anxiety disorder also satisfy criteria for depression.
◆ Right-sided subcortical lesions may be more common in anxiety 
disorder, while left-sided pathology, usually involving cortical regions, is more likely when anxiety and depression coexist.
(2)
Serotonergic abnormalities are also likely to be relevant.
(a) Course and prognosis
Anxiety in the acute post-stroke phase is associated with high mortality rates, comparable to those in depressed patients.
Emotionalism (abnormal crying or laughing)
Emotionalism is usually mood-congruent and is triggered by sad or emotional events. Most patients have some degree of voluntary control.

Emotionalism occurs in a quarter of patients during the ﬁ  rst year 
post-stroke, with a peak in the ﬁ  rst month and decreasing gradually 
thereafter.
(7) It is associated with the severity of depression and 
with left-anterior lesions disrupting serotonergic pathways.
The ﬁ  rst step in treating the psychiatric manifestations of stroke is 
for these to be recognized, and patients need to be routinely assessed for the presence of psychiatric symptoms.
Treatment
Double-blind placebo-controlled trials using nortriptyline, trazo-
done, and selective serotonin reuptake inhibitors ( SSRI s) have 
shown these drugs to be effective.(4) Improvement in depression

shown these drugs to be effective.(4) Improvement in depression 
also results in lasting improvement in cognition and physical activ-ity. Treatment within 3 months of stroke may be followed by the best outcome.
The treatment of anxiety symptoms has been less well docu-
mented. Short-acting benzodiazepines, buspirone, and SSRIs are the main pharmacological approaches. The usefulness of psycho-therapeutic or behavioural interventions has not been established 5.3.2 psychiatric aspects of neurological disease

SECTION 5  psychiatry and medicine 1072
and may depend on the severity of symptoms and cognitive impair-
ment.
Emotionalism responds well to treatment with SSRIs and tricy-
clic antidepressants, even in those without associated depression.
The neurological and cognitive features of Parkinson’s disease are dealt with in Chapter 4.1.6 and only commonly encountered psy-chiatric symptoms will be considered here.
Its overall prevalence is approximately 40 per cent.(8) Depressive 
symptoms are more common early in the disease (50 per cent) and in those with onset before the age of 55. For many people, adapta-tion to the disease results in a return to normal mood. Depression becomes more frequent again in the advanced stages of the disease, particularly in those with rapidly progressive disability.
Major depression is commoner in those with akinetic Parkinson’s

Major depression is commoner in those with akinetic Parkinson’s 
disease (38 per cent) than in those with classical forms of the disease (15 per cent), but dysthymia is equally common in both. Depression, severe in some patients, has also been reported in the ﬁ  rst few 
weeks after bilateral subthalamic stimulation, a successful treat-ment for the motor symptoms of Parkinson’s disease,
(9) but mood 
changes were less commonly observed a year after surgery.
◆ Anxiety, agitation, and depressed mood are prominent.
◆ Depressive symptoms are not closely associated with the severity 
of motor signs, but may be more severe during ‘off’ periods and 
are commoner in those with cognitive impairment.
◆ Early awakening, motor retardation, and apathy in the absence 
of mood abnormalities may not be indicative of depression.
◆ Major depression is associated with functional deterioration at 
1-year follow-up.(10)

◆ Three-quarters of patients with depression also fulﬁ  l criteria for 
anxiety disorder, but only 10 per cent have symptoms of anxiety in isolation.
(11)
(b) Mechanisms underlying depression
Studies using PET have suggested that depression and anxiety in Parkinson’s disease are associated with a speciﬁ  c loss of dopamine 
and noradrenaline innervation in the limbic system.
(12) Post-
mortem studies have also described loss of dopaminergic neurones in the ventral tegmental area.
(13) Degeneration of these neurones 
leads to dysfunction of the orbitofrontal cortex with secondary effects on the serotonergic cell bodies of the dorsal raphe.
(5)
(c) Management

(5)
Optimal control of neurological symptoms may lead to improve-ment in depression and should be a management aim. Repeated assessment may be needed to differentiate features of the disease, such as apathy, from the symptoms of depression.
There are few studies describing the treatment of depression in Parkinson’s disease. When antidepressants are clinically indicated because of the severity or persistence of symptoms, the antidepressant profile of side-effects should be considered. 
Antidepressants with strong anticholinergic effects, such as ami-triptyline, may increase cognitive impairment and SSRIs may be preferable. Electroconvulsive treatment is also effective for Parkinson’s disease patients with depression and may also tran-siently improve motor symptoms.

◆ Up to 40 per cent of patients on long-term treatment experience 
visual hallucinations.
◆ Long duration of illness, age, cognitive impairment, and depres-
sion are associated with visual hallucinations.
◆ Visual hallucinations in clear consciousness are usually fully 
formed images of people or animals, non-threatening, ﬂ  eeting, 
and stereotyped. They are recurrent and tend to occur at night, more commonly in the ‘on’ periods.
◆ Sleep disturbances (fragmented sleep, alteration of sleep rhythms, 
and vivid dreams) often precede daytime hallucinations and may be part of a continuum.
◆ Delusions are less frequent than hallucinations but are more 
stressful and difﬁ  cult to manage. They are usually paranoid, with 
conspiracy and inﬁ  delity themes.
◆ Severe psychosis is associated with institutional placement, 
progressive dementia, and increased risk of death (over a quarter of patients within 2 years).
(b) Mechanisms

Psychotic symptoms may represent intrusion of REM sleep imag-ery into wakefulness. They may be more frequent in those receiving anticholinergics and dopamine agonists, but there is no clear association with dosage or duration of treatment. Stimulation of hypersensitive dopaminergic receptors in the nigrostriatal system by dopaminergic drugs may explain psychosis early in the disease, but it is unlikely to explain late psychosis. The therapeutic efﬁ  cacy 
of atypical neuroleptics suggests a role for mesolimbic dopaminer-gic and serotonergic pathways. Cholinergic deﬁ  ciency may also be 
relevant, in patients with dementia and atrophy of the nucleus basalis.

In patients with clouded consciousness, infection, cerebrovascular accidents, and other relevant pathologies need to be excluded. Revision of dopaminergic medication should come next, with reduction of polypharmacy and dose tapering. Anticholinergics, selegiline, amantadine, and dopamine agonists may need to be discontinued, as they are more likely to trigger psychosis.
In most patients antipsychotic drugs are needed, as dopaminergic medication is needed to preserve acceptable motor function. Atypical neuroleptics such as clozapine, with its low D2 receptor afﬁ nity and few extrapyramidal side-effects, are preferable to typi-

cal neuroleptics. Clozapine is effective at doses of less than 100 mg per day. Initial recommended doses of 6.25 to 12.5 mg daily should be gradually increased until the symptoms are controlled. The dan-ger of agranulocytosis and the need to monitor the blood picture

1073
are the main drawbacks, and other atypical neuroleptics (particu-
larly quietiapine) may be preferable. Cholinesterase inhibitors may also be helpful in treating psychotic symptoms in patients with cognitive impairment.
Dopamine dysregulation syndrome
The syndrome is characterized by the compulsive use of dopami-nergic medication beyond that needed to control motor symptoms. It is commoner in males with young onset and may affect 4 per cent of patients. Drug-hoarding and drug-seeking behaviour, impaired social functioning, aggression, and reluctance to reduce medication despite severe dyskinesias are common features. Hypomania and frank psychosis may follow.
(14)
(a) Management
Reduction of medication resolves symptoms, but a withdrawal state characterized by dysphoria and irritability follows. Treatment is difﬁ  cult and often unsuccessful, and primary prevention is 
preferable.
Tourette syndrome
The syndrome is characterized by motor and phonic tics of ﬂ  uctu-
ating severity.

◆ Motor tics appear early, between the ages of 3 and 8 years. Simple 
tics, e.g. eye blinking, are followed by complex stereotypies(i.e. touching, licking). Phonictics (snifﬁ  ng, throat clearing) 
appear later.
◆ Severity of tics peaks by the age of 20 and may lessen thereafter, 
but total recovery is rare. Severe cases may start in adulthood.
◆ Tics, preceded by premonitory urges, occur many times a day 
and are exacerbated by anxiety, boredom, fatigue, and excitement and lessened by alcohol, relaxation, and sleep. Patients may be able to suppress tics for long periods at the expense of a build-up of tension.
◆ Coprolalia (utterance of obscenities), copropraxia (obscene 
gestures), echolalia and echopraxia (repetition of words and actions), and self-harm are also common.
T ourette syndrome is part of a spectrum that includes transient

T ourette syndrome is part of a spectrum that includes transient 
childhood tic disorders. Secondary tic disorders following trauma, encephalitis, rheumatic fever, and metabolic and toxic encepha-lopathies, and those present in inherited degenerative conditions such as Huntington’s disease and neuroacanthocytosis, need to be considered in the differential diagnosis.
T ourette syndrome is more frequent in males (4:1). Its prevalence in male adolescents is around 4 per 10 000, but it may be higher (49 per 10 000) in children with behavioural disturbances
(15) and is 
as high as 1 to 3 per cent in school children if a broad deﬁ  nition of 
chronic motor and phonic tics is used.
Aetiology

(15) and is 
Aetiology
Major gene effects with an autosomal mode of inheritance seem likely. Monozygotic twins have a concordance rate between 50 and 70 per cent for the syndrome compared with 10 to 20 per cent for dizygotic twins, and a third of relatives may have features of the syndrome. Several candidate genes have been assessed including dopamine receptors, the dopamine transporter, and various norad-
renergic and serotonergic genes, and although isolated changes in a single locus are unlikely to lead to the syndrome, these alleles could have a signiﬁ  cant cumulative effect. Gestational and perinatal risk

factors may also play a role. Multiple streptococcal infections in the months preceding symptom onset are commoner in T ourette patients than in controls, suggesting that the paediatric autoim-mune neuropsychiatric disorder associated with streptococcal infection (PANDAS) may be the cause of T ourette syndrome in vulnerable patients.
The efﬁ  cacy of dopamine antagonists and SSRIs in the treatment 
of tics and obsessive–compulsive symptoms has implicated dopaminergic and serotonergic pathways and the regions where dopaminergic and serotonergic neurons interact (i.e. striatum, substantia nigra, and prefrontal cortex). The beneﬁ  cial effects of 
basal ganglia deep brain stimulation also point to basal ganglia dysfunction. PET studies have suggested decreased metabolism and blood ﬂ  ow in basal ganglia–thalamo-cortical projection systems.
(16)
Post-mortem studies have not shown consistent abnormalities in 
D1/D2 receptors, and in vivo  receptor-binding studies have been

(16)
D1/D2 receptors, and in vivo  receptor-binding studies have been 
conﬂ  icting, as have structural brain-imaging studies.
Psychiatric comorbidity
◆ About half of the patients meet criteria for other psychiatric dis-
orders,(17) but it is uncertain whether they should be considered 
part of the phenotype.
◆ Depression and anxiety occur in about 25 per cent of patients.
◆ Personality disorder is present in two-thirds of patients. 
Borderline, obsessive–compulsive, and paranoid types are the commonest types.
◆ Attention-deﬁ  cit hyperactivity disorder may be more common 
in males and may have educational and behavioural implica-tions. Wide variations in prevalence have been reported (8 to 80 per cent).
◆ Obsessive–compulsive disorder may be more common in females,

◆ Obsessive–compulsive disorder may be more common in females, 
reaching its peak in late adolescence. Concern for symmetry, violent and sexual thoughts, forced touching, fear of harming self and others, and a need to do things ‘just right’ are common features.
◆ Intellectual ability tends to be normal, but poor performance in 
complex attentional tasks is associated with attention-deﬁ  cit 
hyperactivity disorder.
Explanation and reassurance are often enough in mild cases; for the rest, drug treatment or cognitive-behaviour therapy may be indicated.
Neuroleptics are useful in treating tics. Haloperidol, pimozide, and sulpiride are commonly prescribed and atypical neuroleptics (e.g. risperidone, zipresidone, and olanzapine) are also useful, although few controlled trials are available. Clonidine, a α2 adren-

ergic agonist, is useful, with less severe side-effects. Behavioural interventions (e.g. habit reversal training and bio-feedback  techniques) may also suppress tics. Deep brain stimulation of the 5.3.2 psychiatric aspects of neurological disease

SECTION 5  psychiatry and medicine 1074
centromedian-parafascicular complex of the thalamus or the inter-
nal segment of the globus pallidus is reported to ameliorate tics and self-harm.
Variable success has been achieved with behavioural techniques, 
SSRIs (ﬂ  uoxetine), and risperidone in the treatment of obsessive–
compulsive disorder. The treatment of attention-deﬁ  cit hyperac-
tivity disorder is more controversial, but beneﬁ  ts may follow the 
use of clonidine and stimulants such as methylphenidate, pemo-line, and dextroamphetamine without increasing tic severity.(See also Chapter 9.2.4.)
Multiple sclerosis

Multiple sclerosis is a common neurological disease, with a preva-lence of 50 to 60 per 100 000; it is more common in women. It usu-ally starts between the ages of 20 to 40 and is characterized by multiple demyelinating lesions with a predilection for the optic nerves, cerebellum, brainstem, and spinal cord. In most cases the disease initially follows a relapsing–remitting course, entering a secondary, progressive phase after some years. For a few patients the disease is progressive from the outset.
Purely psychiatric presentations of multiple sclerosis other than 
dementia are rare, but psychiatric symptoms are common in the course of the illness.
◆ Depressive symptoms occur in about 50 per cent of patients in 
cross-sectional studies(18) and their lifetime prevalence is also 
around 50 per cent.

◆ The rates of suicide are more than twice those of the general 
population, and young males and those socially isolated or with drinking problems are at a greater risk.
◆ Low mood, negative thoughts, anhedonia, and suicidal ideation 
are common features of depression.
◆ Fatigue and poor concentration may be features of multiple 
sclerosis and have less diagnostic value.
Euphoria
◆ It is only present in about 10 per cent of patients and is charac-
terized by mild, continuous elation.
◆ It is best considered as an organic type of personality change.
Emotional lability
◆ It is as frequent as euphoria.
◆ Excessive crying is more frequent than laughter.
◆ It tends to be more severe in those with signiﬁ  cant depression.(19)
Psychosis
◆ It is uncommon, but brief affective or schizophrenia-like psycho-

Psychosis
ses may occur in patients with well-established multiple sclerosis, sometimes coinciding with a relapse.
(20)
◆ Persecutory delusions and lack of insight are common.
◆ In most patients these are single episodes lasting 4 to 6 weeks 
that respond well to symptomatic treatment.(a) Mechanisms of psychotic symptoms
Severity of brain disease , as measured by magnetic resonance 
imaging ( MRI ), and duration of illness are not closely correlated 
with depression , but they are a risk factor. The personal and social 
limitations imposed by the disease are an important risk factor for depression.
(18) A genetic predisposition  has been reported in 
multiple sclerosis patients with bipolar illness.
Euphoria  and emotional lability  tend to occur in patients

Euphoria  and emotional lability  tend to occur in patients 
with advanced disease and cognitive impairment and are more closely related to MRI indices of brain damage. MRI lesions tend to cluster around the temporal lobes in patients with psychotic 
symptoms .
(b) Management of psychotic symptoms
All patients should be assessed for the presence of depression. 
Fatigue and poor concentration have limited diagnostic value, as they may be features of multiple sclerosis. Although disease-modi-fying treatments do not increase the overall risk of depression, they may do so in the ﬁ  rst 6 months of treatment in those with a previ-
ous history of depression.
(21) Regular psychiatric assessment in the 
early stages of treatment is, therefore, important.
(c) Treatment of psychotic symptoms

Few studies have assessed the effect of antidepressants in patients with multiple sclerosis, but SSRIs and other antidepressants appear to be effective. Their side-effects need to be carefully considered for their potential to aggravate or improve neurological symptoms. Cognitive-behaviour therapy aimed at improving coping strategies is also useful. Emotional lability  responds well to small doses of 
SSRIs or tricyclic antidepressants but tends to recur when these drugs are discontinued.
Psychotic episodes may require the use of neuroleptics for brief 
periods, but the long-term use of these drugs is rarely required.
Cognitive impairment is present in about 40 per cent of multiple sclerosis patients
(22) and contributes signiﬁ  cantly to the overall

(22) and contributes signiﬁ  cantly to the overall 
disability. The pattern of impairment is characterized by the following:
◆ Attention deﬁ  cits and slowing of information processing speed 
are often the ﬁ  rst manifestations and may be present early in the 
disease.(23)
◆ Memory disturbances, with greater impairment of recall over 
recognition, appear later.
◆ Executive function deﬁ  cits, with poor working memory, abstract 
reasoning, and use of strategy, are common.
◆ Language skills and visuospatial functions tend to be preserved.
Cognitive impairment is greater in those with progressive, severe 
disease, although cases presented as dementia have also been described.
(24) Depression worsens cognitive impairment by slow-

ing down information processing and interfering with learning and working memory. Cognitive impairment correlates with MRI markers of disease severity, in particular brain atrophy.
(a) Management of cognitive impairment
Disease-modifying treatments may slow down cognitive impairment, but evidence is insufﬁ  cient. The same applies to cholinesterase 
inhibitors. Cognitive rehabilitation has so far been disappointing.

1075
Space-occupying lesions
Brain tumours
Their clinical manifestations are determined by location and by the 
effects of raised intracranial pressure. Psychiatric symptoms occur in 50 per cent of patients
(25) and are of three main types:
◆ Confusional states and/or progressive cognitive deterioration 
occur in a third of patients. Disorientation with clouding of con-sciousness, euphoria, apathy, and loss of insight are prominent in those with confusional states. Progressive memory impairment, loss of initiative, and bradyphrenia occur in patients with a more protracted course and may coexist with signs of raised intracra-nial pressure.
◆ Behavioural and mood disturbances occur in 20 per cent of 
patients. Irritability, euphoria, depression, and, less frequently, psychosis are part of the picture.
◆ Paroxysmal disturbances such as poorly formed visual hallucina-
tions and automatisms, indicating temporal lobe involvement, are less common.

Fast-growing tumours are more likely to cause psychiatric symp-
toms (60 per cent in patients with gliomas and 42 per cent in those with meningiomas). Frontal lobe tumours may present with psychi-atric symptoms in the absence of other neurological abnormalities.
(26)
Medial and orbitofrontal tumours lead to emotional symptoms while disinhibition and irritability or marked apathy occurs when the anterior cingulate is involved. Tumours involving the dorsolat-eral prefrontal regions are more likely to produce abnormalities of executive function (planning, goal-directed behaviour, ability to monitor effective performance). Disturbances of micturition are speciﬁ  cally associated with frontal tumours.
Brain tumours should be suspected in patients with the above

Brain tumours should be suspected in patients with the above 
syndromes or when psychiatric symptoms are accompanied by neurological abnormalities or appear de novo  late in life. Imaging 
usually conﬁ  rms the diagnosis.
Neuroﬁ  bromatosis
There are two types of neuroﬁ  bromatosis, both inherited as auto-
somal dominant disorders.
Neuroﬁ  bromatosis 1  is the commonest (incidence 1/3000) and is 
characterized by cutaneous manifestations (café-au-lait pigmenta-tion) and neuroﬁ  bromas, which are benign nerve sheath tumours. 
Gliomas and hamartomas, especially in the eye and optic pathways, and bone dysplasia are also features. Severe learning disability occurs in 4 per cent of patients, but milder cognitive impairment is commoner (80 per cent of cases). Attentional difﬁ  culties are com-
mon and a third of patients fulﬁ  l criteria for attention-deﬁ  cit 
hyperactivity disorder. Perceptual and executive functions are worse than memory functions.

(27, 28)  Epilepsy is twice as common 
as in the general population. Ventricular enlargement and T2 MRI 
hyperintensities in the basal ganglia, internal capsule, thalamus, brainstem, and cerebellum not closely related to the severity of the learning disability are often present.
Neuroﬁ  bromatosis 2  is much less common (incidence 1/40 000) 
and is characterized by bilateral vestibular schwannomas, which may also occur in other peripheral nerves. Meningiomas and epen-dymomas also occur. Hearing loss, vestibular disturbances, and cataracts are the commonest clinical presentations. Cognition is 
normal.
The loci for neuroﬁ  bromatosis 1 and 2 have been located to 17q  
11.2 and 22q 12.2 respectively. The rate of spontaneous mutations is high and both genes may have tumour-suppressant roles.

normal.
Management  is aimed at dealing with attention-deﬁ  cit hyperac-
tivity disorder, learning disability, and epilepsy.
Tuberous sclerosis
Tuberous sclerosis is a rare autosomal dominant disorder with a prevalence of 1/27 000, variable expressivity, and a high spontane-ous mutation rate. There is genetic heterogeneity, with loci described in chromosomes 9 and 16. It is characterized by the presence of skin lesions (adenoma sebaceum), calcified subependymal nodules (tubers), and cortical dysplasias. Hamartomas and other neoplasms of the brain, heart, kidney, and liver are part of the picture.
◆Epilepsy  occurs in 60 to 80 per cent of patients, and infantile 
spasms, a type of epilepsy, with onset in the ﬁ  rst 6 months of life, 
are particularly common.

◆ Moderate to severe learning disability  is present in over 50 per 
cent of patients and is associated with the presence of infantile spasms and poorly controlled epilepsy.
(29)
◆Autism  is 200 times more common in tuberous sclerosis than in 
the general population and tuberous sclerosis occurs in 1 per cent of autistic patients.
(30)
◆ The number of cortical tubers detected by MRI is a marker of dis-
ease severity and is related to the degree of learning disability.(31)
The presence of tubers in the temporal lobes has been reported to be associated with autism in patients with tuberous sclerosis.
Management  is aimed at control of epilepsy and learning 
disability.
Lishman, W.A. (1997). Organic psychiatry: psychological consequences of 
cerebral disorder  (3rd edn). Blackwell, London.

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Burn, D.J. and Tröster, A.I. (2004). Neuropsychiatric complications of 
medical and surgical therapies for Parkinson’s disease. Journal of 
Geriatric Psychiatry and Neurology ,17, 172–80.
Siegert, R.J. and Abernethy, D.A. (2005). Depression in multiple sclerosis: a 
review. Journal of Neurology, Neurosurgery and Psychiatry ,76, 469–75.
Amato, M.P ., Zipoli, V ., and Portaccio, E. (2006). Multiple sclerosis-related 
cognitive changes: a review of cross-sectional and longitudinal studies. 
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Albin, R.L. and Mink, J.W. (2006). Recent advances in T ourette syndrome 
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Prather, P . and de Vries, P .J. (2004). Behavioral and cognitive aspects of 
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 2. Robinson, R.G. (1998). Relationship of depression to lesion location. 
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emotional disorders following vascular brain injury , pp. 94–124. 
 3. Sharpe, M., Hawton, K., Seagroatt, V ., et al. (1994). Depressive disorders 
in long-term survivors of stroke: associations with demographic and 
social factors, functional status, and brain lesion volume. The British 
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versus late antidepressant treatment on physical impairment associated with poststroke depression: is there a time-related therapeutic window? The Journal of Nervous and Mental Disease ,191, 645–52.
 5. Mayberg, H.S. and Solomon, D.H. (1995). Depression in Parkinson’s 
disease: a biochemical and organic viewpoint. Advances in Neurology ,
65, 49–60.

5. Mayberg, H.S. and Solomon, D.H. (1995). Depression in Parkinson’s 
65, 49–60.
 6. House, A., Dennis, M., Mogridge, L., et al. (1991). Mood disorders in 
the year after stroke. British Journal of Psychiatry ,158, 83–92.
 7. House, A., Dennis, M., Molyneau, A., et al. (1989). Emotionalism after 
stroke. British Medical Journal ,198, 991–4.
 8. Brown, R. and Jahanshahi, M. (1995). Depression and Parkinson’s 
disease: a psychosocial viewpoint. Advances in Neurology ,65, 61–84.
 9. Berney, A., Vingerhoets, F., Perrin, A., et al. (2002). Effect on mood of 
subthalamic DBS for Parkinson’s disease: a consecutive series of 24 patients. Neurology ,59, 1427–9.
10. Starkstein, S.E., Mayberg, H.S., Leiguarda, R., et al. (1992). A prospective 
longitudinal study of depression in patients with Parkinson’s disease. 
Journal of Neurology ,Neurosurgery and Psychiatry ,55, 377–82.

11. Menza, M.A., Robertson–Hoffman, D.E., and Bonapace, A.S. (1993). 
Parkinson’s disease and anxiety: comorbidity with depression. Biological Psychiatry ,34, 465–70.
12. Remy, P ., Doder, M., Lees, A., et al. (2005). Depression in Parkinson’s 
disease: loss of dopamine and noradrenaline innervation in the limbic system. Brain: a Journal of Neurology ,128, 1314–22.
13. Paulus, W. and Jellinger, K. (1991). The neuropathologic basis 
of different clinical subgroups of Parkinson’s disease. Journal of 
Neuropathology and Experimental Neurology ,50, 743–55.
14. Giovannoni, G., O’Sullivan, J.D., Turner, K., et al. (2000). Hedonistic 
homeostatic dysregulation in patients with Parkinson’s disease on 
dopamine replacement therapies. Journal of Neurology, Neurosurgery, 
and Psychiatry ,68, 423–8.

15. Robertson, M.M. and Stern, J.S. (1997). The Gilles de la T ourette 
syndrome. 
Critical Reviews in Neurobiology ,11, 1–19.
16. Tanner, C.M. and Goldman, S.M. (1997). Epidemiology of T ourette 
syndrome. Neurologic Clinics ,15, 395–402.
17. Eidelberg, D., Moeller, J.R., Antonini, A., et al. (1997). The metabolic 
anatomy of T ourette’s syndrome. Neurology ,48, 927–34.
18. Ron, M.A. and Logsdail, S.J. (1989). Psychiatric morbidity in multiple 
sclerosis. A clinical and MRI study. Psychological Medicine ,19, 887–95.
19. Dark, F.L., McGrath, J.J., and Ron, M.A. (1996). Pathological laughing 
and crying. The Australian and New Zealand Journal of Psychiatry ,
30, 472–9.
20. Feinstein, A., du Boulay, G., and Ron, M.A. (1992). Psychotic illness in

30, 472–9.
20. Feinstein, A., du Boulay, G., and Ron, M.A. (1992). Psychotic illness in 
multiple sclerosis. A clinical and magnetic resonance imaging study. British Journal of Psychiatry ,161, 680–5.
21. Goldman Consensus Group. (2005). The Goldman consensus statement 
on depression in multiple sclerosis. Multiple Sclerosis ,11, 328–37.
22. Rao, S.M., Leo, G.J., Ellington, L., et al. (1991). Cognitive dysfunction 
in multiple sclerosis. II: impact on employment and social functioning. Neurology ,41, 692–6.
23. Feinstein, A., Y oul, B., and Ron, M. (1992). Acute optic neuritis: a 
cognitive and magnetic resonance imaging study. Brain: a Journal of 
Neurology ,115, 1403–15.
24. Hotopf, M.H., Pollock, S., and Lishman, W.A. (1994). An unusual 
presentation of multiple sclerosis. Case report. Psychological Medicine ,
24, 525–8.25. Hecaen, H. and Ajuriaguerra, J. (1956). Troubles mentaux au cours des

24, 525–8.25. Hecaen, H. and Ajuriaguerra, J. (1956). Troubles mentaux au cours des 
tumeurs intracraniennes . Masson, Paris.
26. Ron, M.A. (1989). Psychiatric manifestations of frontal lobe tumours. 
British Journal of Psychiatry ,155, 735–8.
27. Hyman, S.L., Shores, A., and North, K.N. (2003). The nature and 
frequency of cognitive deﬁ  cits in children with neuroﬁ  bromatosis 
type 1. Neurology ,65, 1037–44.
28. Y ohay, K. (2006). Neuroﬁ  bromatosis types 1 and 2. The Neurologist ,
12, 86–93.
29. Jozwiak, S., Goodman, M., and Lamm, S.H. (1998). Poor mental 
development in patients with tuberous sclerosis complex: clinical risk 
factors. Archives of Neurology ,55, 379–84.
30. Fombonne, E., Du Mazaubrun, C., Cans, C., et al. (1997). Autism 
and associated medical disorders in a French epidemiological survey. Journal of the American Academy of Child and Adolescent Psychiatry ,36,
1561–9.

1561–9.
31. Joinson, C., O’Callaghan, F.J., Osborne, J.P ., et al. (2003). Learning 
disability and epilepsy in an epidemiological sample of individuals with tuberous sclerosis complex. Psychological Medicine ,33, 335–44.
5.3.3 Epilepsy
An epileptic seizure has been deﬁ  ned as ‘a clinical manifestation 
presumed to result from an abnormal and excessive discharge of a set of neurones in the brain’ .
(1) A diagnosis of epilepsy applies with 
the recurrence of two or more discrete and unprovoked seizures (febrile and neonatal seizures are excluded from this deﬁ  nition).
Epilepsy is one of the more common neurological disorders.

Epilepsy is one of the more common neurological disorders. 
It carries with it a greater psychiatric morbidity than is to be found in other neurological disorders of comparable severity. Many of its manifestations resemble and may be confused with psychiatric phenomenology. It is often associated with learning difﬁ  culties; it 
may be a manifestation of acquired brain damage or disease; seizures may occur in the course of substance abuse or be caused by psychiatric treatment. For these and for many other reasons psy-chiatrists should be familiar with epilepsy, its manifold aetiologies, presentations, and treatment.
Classiﬁ  cation: epileptic seizures 
and epilepsy
A comprehensive taxonomy should embrace classiﬁ  cations of both

A comprehensive taxonomy should embrace classiﬁ  cations of both 
seizure semiology (i.e. the manifestations of abnormal discharge activity) and of epilepsy syndromes. The position of each seizure type in a seizure classiﬁ  cation system is determined by its clinical 
manifestations, by electroencephalographic changes during the sei-zure, and by the interictal electroencephalographic abnormalities. A classiﬁ  cation of epilepsy syndromes takes into account seizure 
subtype, and also anatomical substrate, aetiology, age of onset, and other characteristics. Seizure classiﬁ  cation is dependent upon enti-
ties that are immediately ascertainable; epilepsy syndrome classiﬁ  -
cation depends upon entities (e.g. neuroanatomical substrate) that are more speculative. The International League Against Epilepsy

1077
(ILAE) has chosen to give the former priority, while recognizing 
the importance of the latter.
A familiarity with terminology, with the more common seizure 
subtypes, and the more commonly encountered epileptic syn-dromes, will assist in an understanding of the psychiatric disorders that occur in patients with epilepsy. The aura is a simple partial seizure, i.e. a seizure of focal onset in which consciousness is retained. It may progress to a complex partial seizure in which consciousness is disturbed, or into a generalized tonic, clonic, or tonic–clonic seizure. It may subside without further development. It rarely lasts for more than a few seconds, although patients often ﬁ nd time estimation difﬁ  cult. It is to be distinguished from the epi-

leptic prodrome, a period characterized by dysphoria, impaired memory and concentration, and minor motor manifestations, which precede the seizure and may last for hours or even days. An automatism may be deﬁ  ned as ‘a state of clouding of consciousness 
which occurs during or after a seizure, and during which the indi-vidual retains the control of posture and muscle tone and performs simple or complex movements without being aware of what is happening’ .
(2) The initial phase, consisting of staring or simple

(2) The initial phase, consisting of staring or simple 
chewing movements, may progress to more complex, stereotyped, and repetitive movements such as fumbling or picking. Automatisms rarely last more than a few minutes and are often very brief. They usually arise from temporal lobe discharges, but may be associated with orbital and mesial frontal lesions. The ictus refers to the period of manifest seizure activity. If this persists for 30 min or more it is described as status epilepticus and constitutes a medical emergency (Table 5.3.3.1).
Seizure types
Partial seizures
Partial seizures have a focal onset and may or may not generalize. They may be simple or complex, depending upon whether or not consciousness remains undisturbed. For this purpose, conscious-ness is deﬁ  ned as the ability to remain aware or to respond.
(a) Simple partial seizures
The content of the simple partial seizure depends upon the site of

The content of the simple partial seizure depends upon the site of 
the focus. One that arises from motor territory may present as a Jacksonian ‘march’ or as a versive turning of the head. Speech arrest may be present. A focus in the primary sensory cortex may give rise to poorly formed sensations. The more elaborate sensations and the psychic symptoms that arise, respectively, from the association cortex and from the mesial frontotemporal structures are more 
likely to progress to complex partial seizures.
(b) Complex partial seizures
These may begin as a simple partial seizure or ‘aura’ , or conscious-ness may be impaired from the beginning. Characteristic auras include epigastric sensations rising into the thorax and olfactory and gustatory hallucinations, elaborated auditory and visual hal-lucinations, complex changes in perception (e.g. micropsia, deper-sonalization), and psychic phenomena such as déjà vu . As discharge

activity spreads, automatic behaviour may supervene or a second-ary generalized seizure may ensue. Complex partial seizures commonly arise from temporal, particularly mesial temporal, structures. Hence the obsolete term ‘temporal lobe epilepsy’ . They may also arise from the orbital and mesial frontal cortices. Complex partial status, previously known as temporal lobe status, is uncommon. It may present as an organic confusional state and may be mistaken for a ﬂ  orid psychosis. Electroencephalography 
will usually conﬁ  rm the diagnosis.
Generalized seizures
Both hemispheres are initially and simultaneously involved, the 
ictal electroencephalographic pattern and motor manifestations are bilateral and consciousness may be impaired from the onset.
Tonic–clonic seizures

This is the common ‘major’ seizure formerly referred to as ‘grand mal’ . A brief tonic phase leads into clonic activity, the entire seizure lasting about 2 min. Generalized seizures may be primary, arising from both hemispheres simultaneously, or they may be due to secondary generalization from a focal onset.
Absence seizures
An absence attack is characterized by abrupt cessation of ongoing activity, a vacant stare, and a period of unresponsiveness lasting from a few seconds to half a minute. The absence may be accompa-nied by brief clonic movements, especially of the eyelids, a reduc-tion in tone causing the body to slump, or automatic movements. Absence seizures occur more commonly during childhood. The 
absence must be distinguished from the complex partial seizure,

absence must be distinguished from the complex partial seizure, 
which it may resemble. Absence status is not uncommon in child-hood and may be mistaken for inattention.
Myoclonic seizures
These are brief shock-like contractions of groups of muscles.
The epilepsy syndromes
The ILAE, in order to embrace a wider range of clinical features than is possible in a classiﬁ  cation based on seizure types, intro-
duced a classiﬁ  cation of seizures and epilepsy syndromes. In this 
classiﬁ  cation the broad division lies between the localization-

related or partial epilepsies, the great majority of which, in adults, is made up of symptomatic epilepsies (i.e. epilepsy arising from a known or suspected cause) and the generalized epilepsies. The characteristics of the partial epilepsies are determined by the function of the cortical site from which the seizure emanates. The more common generalized epilepsies are age-related. Though admirable in concept, the classiﬁ  cation has proved unwieldly and Table 5.3.3.1  Classiﬁ  cation of seizures
1 Localization (partial, focal) seizures
 (a) Simple partial seizures
 (b) Complex partial seizures
 (c) Partial seizures evolving to secondary generalized seizures
2 Generalized seizures
 (a) Absence seizures
 (b) Myoclonic jerks (c) Clonic seizures
 (d) Tonic seizures
 (e) Tonic–clonic seizures
 (f) Atonic seizures5.3.3 epilepsy

SECTION 5  psychiatry and medicine 1078
the terminology clumsy: as such it seems unlikely to displace the 
seizure-type classiﬁ  cation.
The cumulative incidence (i.e. lifetime risk) is 3.4 per cent for 
males, 2.8 per cent for females, but the prevalence is on ly 7 per 1000. 
This is because prevalence represents the balance between newly diagnosed cases and permanent remission or death, and epilepsy has a good prognosis with 76 per cent of newly diagnosed cases entering long-term remission.
(3) Approximately half can be classi-
ﬁ ed as partial seizures and 40 per cent as generalized. Prognosis 
varies according to the epilepsy subtype, with partial epilepsy hav-ing a poorer outcome. Consequently, people who attend a hospital clinic are unrepresentative, in that they are more likely to have treatment-refractory partial seizures along with the other adverse prognostic factors such as mental handicap, neurological dysfunc-tion, or psychiatric disorders.
Aetiology

Aetiology
Aetiology varies according to the age of onset. In childhood- and adolescence-inherited disorders of metabolism, ante- and perinatal complications, infection, migrational errors, and the consequences of febrile convulsions predominate, in middle life trauma and tumour are most common, and in advanced years cerebrovascular disease and degenerative disorders are predominant.
Only one-quarter to one-third of cases of epilepsy are due to 
known causes. Many others fall into recognizable syndromes about which much is understood. The partial epilepsies are, by deﬁ  nition, 
due to focal areas of damage and dysfunction usually involving the cortex. However, although the site may be suggested by the seizure semiology, comprehensive investigation may fail to identify any abnormality. Even when it does so, the radiological appearance may lack aetiological speciﬁ  city. Some generalized seizures may be 
identiﬁ  ed as primary generalized epilepsy syndromes; for example,

identiﬁ  ed as primary generalized epilepsy syndromes; for example, 
juvenile myoclonic epilepsy. These are of uncertain aetiology, though genetic factors are considered important; onset is in child-hood or adolescence and the prognosis favourable.
In psychiatric practice seizures may arise iatrogenically; they are 
usually due to pharmacotherapy, less commonly to electroconvul-sive therapy. They may result from the overhasty withdrawal of benzodiazepines or to the use of antidepressant or antipsychotic drugs, most of which are epileptogenic. Such seizures are thought to be provoked and do not form grounds for a diagnosis of epilepsy. Adjustment of drug dosage is usually all that is required. Provoked seizures may also occur during alcohol intoxication (‘rum ﬁ  ts’) or 
withdrawal; a genetic predisposition may play a part.
Diagnosis
The diagnosis of epilepsy depends ﬁ  rst and foremost on historical

Diagnosis
The diagnosis of epilepsy depends ﬁ  rst and foremost on historical 
information; the patient’s own account of the seizure and the observations of a reliable informant are of tantamount importance. A family history of epilepsy should be sought; age of onset should be determined when possible. A history of birth complications, febrile ﬁ  ts, early head injury, or cerebral infection is of particular 
importance in seizures starting in childhood, adolescence, or early adult life. In middle life symptoms suggestive of developing intra-cranial pathology and in later life cerebrovascular and degenerative disorders should be sought. The clinician should be aware of 
speciﬁ  c circumstances and situations that may provoke seizures:

speciﬁ  c circumstances and situations that may provoke seizures: 
alcohol or substance abuse, prescribed drugs that have epilepto-genic properties, and intermittent photic stimulation. Physical examination will detect not only gross congenital abnormalities such as tuberosclerosis, but also more subtle features, for example facial or skull asymmetries. The differential diagnosis varies according to age group, but will include vasovagal attacks and pseudoseizures, particularly in the young, vertigo and transient ischaemic attacks in the elderly, and cardiogenic syncope, hypogly-caemic episodes, and migraine at any age.
The role of physical investigation is to conﬁ  rm the diagnosis of

The role of physical investigation is to conﬁ  rm the diagnosis of 
epilepsy when this is in doubt and to identify the cause; it may also help to determine the type of epilepsy and, in the partial epilepsies, the site of seizure onset. Magnetic resonance scanning is now widely available and all new cases of adult-onset epilepsy and patients of any age with partial epilepsy should have the beneﬁ  t of this 
technology. A sleep electroencephalograph is still mandatory and may be invaluable not only in differential diagnosis, but in deter min-
ing the epilepsy subtype and seizure localization. Video-telemetry is invaluable when there is continuing diagnostic uncertainty, and in those cases in which precise localization is necessary for presurgical assessment. Functional neuroimaging may also aid localization.
In psychiatric practice epileptic seizures must be distinguished

In psychiatric practice epileptic seizures must be distinguished 
from psychogenic pseudoseizures, panic attacks, and aggressive episodes. The pseudoseizure may take different forms: the patient 
may fall or slump to the ground and remain still as in a syncopal 
attack; or there may be jerking or thrashing of limbs resembling a major tonic–clonic seizure. The absence of tongue-biting, inconti-nence, or signiﬁ  cant injury is often said to distinguish the pseudo-
seizure from the epileptic seizure, but such guides are frequently unreliable. A history of other conversion disorders or illness behav-iour may be obtained, but pseudoseizures also occur in individuals with epilepsy. A detailed description of the attack from the patient and from a witness will be of the greatest assistance in diagnosis, but when in serious doubt video-telemetry may offer a deﬁ  nitive

answer. Other useful investigations include serum prolactin levels, which rise postictally to reach a peak between 20 and 30 min after a major epileptic seizure. Episodes of panic are sometimes mistaken for epileptic seizures. Extreme anxiety, especially when accompa-nied by hyperventilation, may lead to a subjective diminution in awareness, altered perception, and other features suggestive of complex partial seizures. The context in which the attack occurs, a description of initial autonomic arousal, and other symptoms of anxiety should lead to the correct diagnosis. Sudden outbursts of aggressive behaviour, particularly when out of character and con-text, often give rise to suspicions of epilepsy. Aggression, especially directed aggression, is extremely unusual as a feature of the epilep-tic seizure, though it may occasionally be seen during the phase of postictal confusion or postictal psychosis.
The psychiatric consequences of epilepsy

The prevalence of psychiatric morbidity among persons with epilepsy is greater than in the general population, but the increase in prevalence will vary according to the type of epilepsy, the pres-ence and extent of brain damage, and the presence of cognitive and physical disability. The more reliable studies are drawn from

1079
 community samples. Of children between the ages of 5 and 14 years, 
29 per cent showed some psychiatric disorder compared with 6.8 per cent of the general population. The ﬁ  gure rose to 58 per cent 
when brain damage was present.
(4) Pond and Bidwell(5) surveyed 
14 general practices and reported a prevalence of 29 per cent in 
adults, increasing to over 50 per cent in patients with temporal lobe epilepsy. Neurotic disability accounted for the great majority of cases. Psychiatric morbidity is over-represented in clinic attenders and in patients with partial epilepsy.
(6)
Personality disorder and social development
Notions of an epileptic personality arising out of a hereditary ‘taint’ persisted well into the present century. The person with epilepsy was said to be explosively aggressive, rigid, egocentric, and irritable. These beliefs were formed by observations of often oversedated inmates of epileptic institutions. The concept of a speciﬁ  c epileptic

personality has now largely been abandoned, though it is acknowl-edged that some features associated with, but not speciﬁ  c to, 
epilepsy may exercise a powerful inﬂ  uence on personality develop-
ment. Many of these are consequences of brain damage rather than epilepsy as such. Thus learning difﬁ  culties, leading to limited edu-
cational opportunity, adult unemployment, and socioeconomic disadvantage may be signiﬁ  cant personality determinants. But even 
in the epileptic individual without brain damage the sedative actions of anticonvulsant medication, the continuing stigma of seizure activity, and the social and occupational constraints are not without their effects on the developing personality.
A particular link between temporal epilepsy and abnormalities of 
personality has long been debated
(7) and certain exaggerated traits 
(e.g. hypergraphia) are consistently reported,(8) but many of the 
personality difﬁ  culties may be explained by the refractory nature of

personality difﬁ  culties may be explained by the refractory nature of 
temporal lobe seizures and the need for increased medication.
Psychoses
(a) Chronic interictal psychoses
Throughout the ﬁ  rst half of this century the relationship between 
epilepsy and schizophrenia was debated at length, usually in terms of whether the presence of one condition encouraged or discour-aged the development of the other—the afﬁ  nity and antagonism 
hypotheses, respectively. In recent years, particularly following the publication of Slater’s seminal studies,
(9) informed opinion has 
moved ﬁ  rmly behind the ﬁ  rst view. Epidemiological studies based 
on national registers(10,11)  ﬁ nd a higher prevalence of chronic 
psychosis in epileptic subjects than in the general population. A neurology outpatient clinic study
(12) reported schizophrenia to

(12) reported schizophrenia to 
be nine times more common in epilepsy than in a migraine control group. The onset, cause, and clinical characteristics are, to a very large extent, indistinguishable from those of more usual forms of schizophrenia, although negative symptoms occur less frequently, thought disorder is rarely encountered and the outcome may be more benign. Psychosis usually develops 11–15 years following the onset of epilepsy. The aetiology remains uncertain. Cases in which the epilepsy takes the form of complex partial seizures arising from 
the mesial temporal or frontal lobes are over-represented; there

the mesial temporal or frontal lobes are over-represented; there 
may be a slight left-sided predominance. A family history of schizo-phrenia was thought to be unusual, but some recent studies have cast doubt on this assumption. Neuropathological examina-tion, more readily available with the increasing practice of epilepsy surgery, has proved less informative than had been hoped, but 
subjects undergoing temporal lobectomy for resection of small neurodevelopmental lesions, e.g. ganglioglioma, dysembryoplastic 
neuroepithelioma (DNET)
(13) appear at greater risk of developing 
a post-operative chronic interictal psychosis. The results of struc-
tural neuroimaging studies have been inconclusive with reports of both reduction and increase in amygdala size. The risk of bipolar illness or affective psychosis does not appear to be increased in epilepsy.
(b) Postictal psychosis

The other common form of epileptic psychosis develops following an exacerbation of seizure activity. Because of this close temporal relationship the instrumental role of epilepsy in the aetiology of the psychosis is not open to question. The salient characteristics have been described.
(14) The psychosis usually occurs following a 
cluster of complex partial seizures usually followed by secondary generalization. Characteristically, the subject appears to make a complete recovery, but 1 to 2 days later, the so-called lucid interval, becomes ﬂ  oridly psychotic. Affective, schizophrenic, and confu-
sional elements may be present. An electroencephalogram recorded at the time shows increased focal discharge activity, though less than would be seen in partial status. Spontaneous recovery is to be expected, usually within a week of onset. The ﬁ  rst episode is usu-
ally delayed until early adult life, a decade and a half after the ﬁ  rst

ally delayed until early adult life, a decade and a half after the ﬁ  rst 
seizure. Half of those affected will have further similar episodes. Fifteen to 20 per cent will progress to develop a chronic interictal psychosis. Bilateral EEG discharges are seen more commonly in those patients who develop postictal psychosis. Functional neuro-
imaging at the time of the psychosis demonstrates relative mesial 
temporal hyperperfusion suggestive of an active process, either continuous seizure discharge or seizure inhibition.
Rarely, the introduction of certain anticonvulsant drugs may 
seem to precipitate psychotic episodes. This may be associated with rapid seizure control and give rise to the term ‘forced normaliza-tion’ .
(15) In recent years vigabatrin has seemed to be the drug most 
responsible.
Sexual function

A diminution in sexual interest, a decrease in activity, and impaired performance are the most common aspects of sexual dysfunction in epilepsy. Men have been studied more thoroughly than women. In patients receiving antiepilepsy drugs libido may be diminished and erectile potency impaired. Levels of free testosterone, the biologi-cally active hormone, may be diminished. Sperm concentrations may be reduced, morphological abnormalities may occur more 
commonly and mobility may be reduced. Menstrual irregularities 
are increased in women with epilepsy and are related to seizure frequency, polytherapy with antiepilepsy drugs, and the use of sodium valproate. Infertility, ovulation, and the polycystic ovarian syndrome occur more commonly. Hyposexuality may be more pronounced in patients with partial epilepsy, but this may simply reﬂ ect the refractory nature of partial epilepsy and the greater

amount of drugs prescribed.
(16,17)
Epilepsy and crime
There is an association between epilepsy and criminal activity. Male epileptics are three times more likely to receive a criminal convic-tion,
(18) in England and Wales between 0.7 and 0.8 per cent of the 5.3.3 epilepsy

SECTION 5  psychiatry and medicine 1080
prison population suffers from epilepsy, a ﬁ  gure considerably higher 
than in the general population,(19) but the pattern of offence does 
not differ. The reasons for this are unclear. Low intelligence and low socioeconomic class are common to both epilepsy and prison populations; the role of brain damage as distinct from epilepsy has not been fully evaluated. Crimes of violence in the context of disturbed ictal or postictal behaviour do occur, but are extremely rare.
(20)
Neurotic illness

(20)
Neurotic illness, more especially anxiety and depression, largely account for the increased psychiatric morbidity that is to be found in patients with epilepsy. These disorders have few distinctive char-acteristics. They may be explained by the adverse social, educational, and economic disadvantages that confront people with epilepsy. A phobic anxiety akin to agoraphobia may be seen in some indi-viduals who fear the onset of a seizure in public places. Obsessive–compulsive disorder does not seem to occur more commonly in epilepsy.
Epilepsy and suicide
Suicide is increased ﬁ  vefold among patients with epilepsy, but is 
considerably higher among those with temporal lobe epilepsy.(21)
Among patients presenting with self-harm, epileptic subjects are over-represented from ﬁ  ve- to sevenfold.
(22)
Treatment
Seizure control is most effectively achieved through the appropriate 
use of anticonvulsant drugs. The use of behavioural techniques to

(22)
Treatment
use of anticonvulsant drugs. The use of behavioural techniques to 
inhibit seizure activity holds promise, but is still in its infancy. Surgical treatment is increasingly available, but should only be 
considered for those patients who have failed repeatedly to respond to drug therapy and who have resectable lesions. Drug treatment should aim to achieve seizure control through the use of a single anticonvulsant drug, thus minimizing unwanted side-effects. This should be possible in the great majority of patients. If a ﬁ  rst-choice 
drug fails, a second-choice drug should be substituted. Polytherapy may be necessary, notably in the management of partial seizures, but should be avoided wherever possible. Most ﬁ  rst-line drugs,

drug fails, a second-choice drug should be substituted. Polytherapy may be necessary, notably in the management of partial seizures, but should be avoided wherever possible. Most ﬁ  rst-line drugs, 
except phenytoin, are described in Chapter 6.2.6. Phenytoin, although relatively toxic, especially to the cerebellum, is an effective anticonvulsant and still widely prescribed. Serum monitoring is 
particularly important. More recently introduced drugs include 
topiramate and levetiracetam. The benzodiazepines, clobazam and clonazepam, may be used in adjunctive therapy. Lamotrigine and levetiracetam appear to be as efﬁ  cacious as the longer established 
drugs and have less side-effects. There is little place for either phe-nobarbitone, which is unduly sedative and may cause depression and behavioural disturbance especially in children and adolescents, or vigabatrin, which may cause visual ﬁ  eld constrictions. Vigabatrin, 
and to a lesser extent topiramate may cause psychotic episodes.

and to a lesser extent topiramate may cause psychotic episodes. 
The need for continuing anticonvulsant therapy should be reviewed by a specialist neurologist once the patient has been free of seizures for 2 years. For a more detailed account of the management of epilepsy and of status epilepticus the reader is referred to Shorvon et al.
(23)
The treatment and outcome for psychogenic seizures have 
received increasing attention. The importance of early diagnosis is emphasized.(24) Psychological treatment, particularly cognitive–
behavioural therapy, can be effective. Reduction or cessation of symptoms can be achieved in at least half of the cases within a 6–12 month period.
Asbury, A.K., McKhann, G.M., et al. (eds.) (1992). Diseases of the nervous 
system  (2nd edn). W.B. Saunders, Philadelphia, PA.
Hopkins, A., Shorvon, S., and Cascino, G. (eds.) (1995). Epilepsy  (2nd edn). 
Chapman & Hall Medical, London.

Lishman, W.A. (1998). Organic psychiatry  (3rd edn). Blackwell Science, 
Oxford.
Trimble, M.R. (1991). The psychoses of epilepsy . Raven Press, New Y ork.
 1. Hopkins, A. and Shorvon, S. (1995). Deﬁ  nitions and epidemiology of 
epilepsy. In Epilepsy  (2nd edn) (eds. A. Hopkins, S. Shorvon, and G. 
Cascino), pp. 1–25. Chapman & Hall Medical, London.
 2. Fenton, G.W. (1981). Psychiatric disorder of epilepsy: classiﬁ  cation and 
phenomenology. In Epilepsy and psychiatry  (eds. E.H. Reynolds and 
M.R. Trimble), pp. 12–26. Churchill Livingstone, Edinburgh.
 3. Annegers, J.F., Hauser, W.A., and Elveback, L.R. (1979). Remission of 
seizures and relapse in patients with epilepsy. Epilepsia ,20, 729–37.
 4. Graham, P . and Rutter, M. (1968). Organic brain dysfunction and child

 4. Graham, P . and Rutter, M. (1968). Organic brain dysfunction and child 
psychiatric disorder. British Medical Journal ,3, 695–700.
 5. Pond, D.A. and Bidwell, B.H. (1960). A survey of epilepsy in 
fourteen general practices. II. Social and psychological aspects. Epilepsia ,1, 285–99.
 6. Edeh, J., T oone, B.K., and Corney, R.H. (1990). Epilepsy, psychiatric 
morbidity, and social dysfunction in general practice. Neuropsychiatry, 
Neuropsychology and Behavioural Neurology ,3, 180–92.
 7. Bear, D.M. and Fedio, P . (1977). Quantitative analysis of inter-ictal 
behaviour in temporal lobe epilepsy. Archives of Neurology ,34, 454–67.
 8. Waxman, S.G. and Geschwind, N. (1974). Hypergraphia in temporal 
lobe epilepsy. Neurology ,24, 629–36.
 9. Slater, E., Beard, A.W., and Glithero, E. (1963). The schizophrenia-like 
psychoses of epilepsy. British Journal of Psychiatry ,109, 95–150.

10. Bredkjaer, S.R., Mortensen, P .B., and Parnas, J. (1998). Epilepsy and 
non-organic non-affective psychosis. National epidemiological study. British Journal of Psychiatry ,172, 235–9.
11. Stefansson, S.B., Olafsson, E., and Hauser, W.A. (1998). Psychiatric 
morbidity in epilepsy: a case control study of adults receiving disability beneﬁ  t. Journal of Neurology, Neurosurgery and Psychiatry ,64, 238–41.
12. Mendez, M.F., Grau, R., Doss, R.C., et al. (1993). Schizophrenia in 
epilepsy: seizure and psychosis variables. Neurology ,43, 1073–7.
13. Andermann, L.F., Savard, G., Meencke, H.J., et al. (1999). Psychosis 
after resection of ganglioglioma or DNET: evidence for an association. 
Epilepsia ,40, 83–7.
14. Logsdail, S.J. and T oone, B.K. (1988). Post-ictal psychoses. British

14. Logsdail, S.J. and T oone, B.K. (1988). Post-ictal psychoses. British 
Journal of Psychiatry ,152, 246–52.
15. Landolt, H. (1953). Some clinical EEG correlations in epileptic 
psychoses (twilight states). EEG and Clinical Neurophysiology ,5, 121.
16. T oone, B.K. (1995). Epilepsy and sexual life. In Epilepsy  (2nd edn)
(eds. A. Hopkins, S. Shorvon, and G. Cascino), pp. 555–65. Chapman & Hall Medical, London.
17. Hertzog, A.G. and Fowler, K.M. (2005). Sexual hormones and epilepsy: 
threat and opportunities. Current Opinion in Neurology
,18, 167–172.
18. Gudmundsson, G. (1966). Epilepsy in Iceland. A clinical and 
epidemiological investigation. Acta Neurologica Scandinavica ,
25, 7–124.
19. Gunn, J. and Fenton, G.W. (1971). Epilepsy, automatism and crime. 
Lancet ,i, 1173–6.

1081
20. Delgado-Escueta, A.V ., Mattson, R.H., King, L., et al. (1981). The 
nature of aggression during epileptic seizures. New England Journal of 
Medicine ,305, 7110–16.
21. Barraclough, B. (1981). Suicide and epilepsy. In Epilepsy and 
psychiatry  (eds. E.H. Reynolds and M.R. Trimble), pp. 72–6. Churchill 
22. Hawton, K., Fagg, J., and Marsack, P . (1980). Association between 
epilepsy and attempted suicide. Journal of Neurology, Neurosurgery and 
Psychiatry ,43, 168–70.
23. Shorvon, S., Dreifuss, F., Fish, D., et al. (eds.) (1996). The treatment of 
epilepsy . Blackwell Science, Oxford.
24. Reuber, M., Fernandéz, G. Bauer, J., et al. (2002). Diagnostic delay in 
psychogenic non-epileptic seizures. Neurology ,58, 493–5.
5.3.4 Medical conditions 
associated with psychiatric disorder
Seven out of 10 ofﬁ  ce visits to a primary care practitioner are relat-
ed to a chronic illness.(1) There are high levels of association of

ed to a chronic illness.(1) There are high levels of association of 
many of these chronic conditions with psychiatric disorders.(1)
Comorbid medical and psychiatric conditions increase use ofmedical resources and costs, as well as amplify functional impair-ment.
(2) For example, depression is associated with an approxi-
mately 50 per cent increase in medical costs of chronic medical ill-ness, even after controlling for severity of physical illness.
(2, 3)
Dementia is associated with hospital costs up to 75 per cent higher than for non-demented patients.
(4)
As important as a comprehensive knowledge of psychiatric diag-

(2, 3)
(4)
nosis and psychosocial formulation is to a consulting psychiatrist, it is also vital to understand the pathophysiology and clinical char-acteristics of the medical and surgical conditions that frequently coexist with psychiatric disorders. It is also important to know the behavioural and psychiatric side effects of medications and sub-stances. Lacking this data permits only a partial and inadequate approach to diagnosis and treatment.
This section describes general medical disorders associated with 
psychiatric syndromes. The pathophysiology and clinical charac-teristics of the medical disorder are described ﬁ  rst, followed by 
psychiatric syndromes often seen with that diagnosis.
Cardiovascular disorders
Ventricular dysrhythmias

Sudden cardiac death is responsible for 300 000 deaths annually in the United States.
(5,6) Sympathetic nervous system activity increases 
the likelihood of ventricular dysrhythmias(6) especially when there 
is prior ischaemic damage. Sympathetic nervous system stimula-tion, which increases heart rate, can trigger ectopic sites in the myo-cardium, which override normal conductive pathways,  producing potentially fatal dysrhythmias. Either the peripheral sympathetic 
nervous system or the central nervous system can  generate stimuli leading to this phenomenon. Therefore, anxiety and stress may 
increase the risk of dysrhythmia.
(7) Among individuals with pre-
existing heart disease or dysrhythmias, activities which precipitate 
adrenergic discharge may produce ventricular dysrhythmias—for example, public speaking, road rage, and recall of emotionally charged events.

(8) In one series of patients, psychological stressors 
were more reliable triggers of dysrhythmias than physical manoeu-vres such as carotid sinus massage, hyperventilation, and the Valsalva manoeuvre.
(8) Simple and inexpensive non- pharmacological tech-
niques such as relaxation training, hypnosis, and medication have been shown to improve ventricular dysrhythmias.
(8, 9)
Depression has also been associated with lower threshold for ven-
tricular dysrhythmias.(10) Patients with depression exhibit dysregu-
lation of the sympathoadrenal system—hypothalamic corticotropin releasing factor-containing neurons appear to stimulate several autonomic centres involved in regulating sympathetic activity.
(11)
Smith et al.(8) found that deaths within 18 months of a myocardial

(11)
Smith et al.(8) found that deaths within 18 months of a myocardial 
infarction were concentrated among depressed patients with 10 or more premature ventricular contractions per hour. In this group of patients, 83 per cent of mortality was due to ‘arrhythmic deaths’ .
More than 60 million Americans have hypertension. The prevalence among whites is about 15 per cent, but is over 25 per cent in the African–American population. 95 per cent of people with hyperten-sion have primary, or idiopathic, hypertension. The remaining 5 per cent have secondary hypertension, due to conditions or substances such as renal disease, steroids, or oral contraceptives. Managing hypertension reduces the morbidity and mortality of the condition. Constitutional and stress-related factors contribute to hypertension. Patients with hypertension, in general, have a more prolonged vaso-constrictive response to psychological stress than patients with nor-motension,

(12) which may result in both short-term and long-term 
blood pressure elevation due to this interplay of environmental and constitutional factors.
(13)
Myocardial infarction
Myocardial ischaemia often leads to myocardial infarction. Acute myocardial infarction can develop at rest or with normal activity. Deaths associated with acute myocardial infarction occur during the ﬁ  rst few hours after the onset of symptoms, and are the result 
of ventricular ﬁ  brillation. It is important that patients know the 
warning signs and seek care promptly when symptoms develop. Unfortunately, as many as 20 per cent of myocardial infarctions are unrecognized. Denial of acute myocardial infarction symptoms and warning signs by individuals, particularly men, are a frequent source of mortality and morbidity. The roles of gender-speciﬁ  c dif-
ferences in terms of establishing predictors for clinical outcomes is understudied.
(14)
The most common precipitant of myocardial ischaemia among

(14)
The most common precipitant of myocardial ischaemia among 
patients with pre-existing coronary artery disease is stress.(15)
Stress-induced ischaemia is more common than ischaemia induced by physical stressors. Recovery from a myocardial infarction is also highly dependent on psychosocial factors. Ruberman et al .
(16)
 demonstrated that postmyocardial infarction patients, who are 
socially isolated and have high stress levels, have at least four times 5.3.4 medical conditions associated with psychiatric disorder

SECTION 5  psychiatry and medicine 1082
the risk of death, compared to their counterparts who have lower 
levels of stress and isolation. Particularly, lack of a close conﬁ  dant 
predicts negative outcomes after myocardial infarction, including further cardiac events.
(17) In addition, emotional distress after 
myocardial infarction is associated with poorer outcomes in terms of quality of life and psychological adjustment.
(18)
Depression may occur in 31 per cent of patients admitted for 
acute myocardial infarction.(19) Presence of major depressive disor-
der in a patient with cardiac disease has a signiﬁ  cant association 
with morbidity and mortality. Carney et al .(20) found that major 
depressive disorder was the best single predictor of myocardial inf-arction, angioplasty, and death during the 12 months following cardiac catheterization. Patients with a history of myocardial inf-arction and major depressive disorder are up to three to ﬁ  ve times

more likely to die within 6 months of discharge than non-depressed patients following infarction.
(19) As to how depression increases 
risk include hypothalamic–pituitary–adrenocortical and/or sym-pathoadrenal hyperactivity, diminished heart rate responsivity, ventricular instability, myocardial ischaemia due to stress, and alterations in platelet receptors and reactivity.
(21, 22) The data are 
limited, antidepressant treatment, stress management, and relaxa-tion training in patients with coronary artery disease or myocardial infarction and major depression probably reduces mortality.
(23)
Type A and type D personality
Assessment of the patient’s personality and behavioural style is important because type A behavioural patterns increase the risk of a myocardial infarction.
(24) The type A behaviour pattern includes

(24) The type A behaviour pattern includes 
ambitiousness, aggressiveness, competitiveness, impatience, muscle tenseness, alertness, rapid and emphatic vocal style, irritation, cyni-cism, hostility, and an increased potential for anger. Very frequently, such individuals are also hard-working ‘workaholics’ who deny physical or emotional vulnerability. Their self-esteem is often dependent on constant achievement. Unstable cardiac function poses an immediate and ongoing threat to them, and challenges their need to be in control of their environment and bodies. Many clinicians believe that modifying a type A behaviour pattern is an integral part of preventing future myocardial infarctions.
(24) Group 
or individual psychotherapy that reduces type A behaviour and other behavioural risks has been shown to lower the incidence of recurrent infarction and cardiac death in patients with a previous myocardial infarction.
(25)
There has been recent attention to the type D personality con-

(25)
struct.(26, 27) D behaviour is characterized by inhibition of negative 
emotions and avoiding social contacts with others. D personality patients may be at increased risk for cardiovascular morbidity and mortality.
(26) Cortisol may be a mediating factor for this increased 
risk. D personality predicts cardiac events after controlling for con-current stress and anxiety.
(27) Studies are needed to validate this 
personality construct, further deﬁ  ne associations with cardiac out-
come, and develop treatment approaches for patients with this  personality style.
Respiratory disorders
Asthma
Asthma affects between 3 and 5 per cent of the population of the United States. The three hallmarks of the disease are airway inﬂ  am-
mation, airway hyperresponsiveness, and a partially reversible airway obstruction. It is one of the classic ‘psychosomatic diseases’ . Emotional

mation, airway hyperresponsiveness, and a partially reversible airway obstruction. It is one of the classic ‘psychosomatic diseases’ . Emotional 
arousal causes changes in airway tone. The severity of an asthma 
attack is highly correlated with presence of major depressive disor-
der, panic attacks, general anxiety, and level of fear among children, adolescents, and adults.
(28) Asthma patients with psychiatric disor-
ders have worse asthma control, more frequent exacerbations, and worse quality of life than asthma patients without psychiatric disor-ders.
(29) Education, relaxation, biofeedback, and family therapy have 
each shown efﬁ  cacy in the management of asthma.(30) Important in 
the management of asthma is education about the adverse effects of antiasthma medications, which include jitteriness, palpitations, and insomnia. These side effects may require treatment with behavioural and/or psychopharmacological therapies.
Chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease (COPD) have slowly progressive airway obstruction. The course of the disease is punctuated by exacerbations due to pulmonary infection, heart failure, and poor compliance with prescribed therapy. Generally affects middle-aged and older patients. They present with dysp-noea, exercise intolerance, cough, and sputum production. Physical examination reveals lung overinﬂ  ation, prominent use of accessory 
muscles to augment respiration, diminished breath sounds, and diffuse wheezing. As with asthma, pharmacological treatments for COPD can cause psychiatric symptoms, especially higher doses of steroid medications. Patients with COPD must stop smoking; pul-monary function declines faster in smokers who develop COPD than non-smokers who develop COPD.
The chronic hypoxia caused by COPD compromises cognition

The chronic hypoxia caused by COPD compromises cognition 
and mood, which, in turn, can produce delirium, mood lability, mood disorders, and restriction in daily activities. Depression is 
present in 20–60 per cent of COPD patients.
(31) Depression 
adversely affects treatment adherence and may increase risk for poor outcomes. There is considerable evidence that supplemental oxygen improves cognitive function and quality of life.
(30)
Unfortunately, mood improvement with supplemental oxygen has not been conclusively demonstrated.
Panic attacks are reported in up to 38 per cent of patients with 
COPD.
(32) Benzodiazepines, which are highly effective for controlling

COPD.
(32) Benzodiazepines, which are highly effective for controlling 
panic attacks, have limited usefulness in patients with COPD because they can suppress respiratory function and if used chronically result in tolerance and dependence. Carbon dioxide likely plays a role in promoting panic attacks; carbon dioxide levels increase with COPD disease progression. Antidepressants are useful in patients with COPD who develop panic attacks. Low-dose neuroleptic medications (e.g. 0.5–1.0 mg risperidone orally two to three times daily) are also sometimes used for severe fear and panic, especially in intensive care unit settings (e.g. when weaning the patient from a respirator). Neuroleptics do not directly suppress respiration, though caution must be exercised so that the sedation induced by neuroleptics—potentially combined with other sedating agents—does not reduce respiratory effort beyond that required to maintain adequate oxy-

genation. Function must also be monitored to ensure that neurolep-
tic use does not affect cardiac conduction or cause dysrhythmias.
Pulmonary embolism
Patients with psychiatric disorders, including bipolar disorder,  anxiety disorder, and schizophrenia, are at increased risk for pul-monary embolism.
(33) Embolism may account for a portion of the

1083
excess risk of death among people with schizophrenia, even after 
controlling for blood pressure, cholesterol, body mass index, smok-ing, exercise, alcohol intake, and education level.
(34) Most throm-
boemboli originate in the deep veins of the thigh. The diagnosis of pulmonary embolus is often missed because the clinical ﬁ  ndings 
are non-speciﬁ  c. They include dyspnoea, pleuritic chest pain, hae-
moptysis, tachypnoea, and wheezing or crackles on pulmonary examination. Number of factors predispose to pulmonary throm-boemboli: cancer, stroke, myocardial infarction, congestive heart failure, sepsis, pregnancy, lower extremity fractures, major surgical procedures, polycythaemia vera, and paroxysmal nocturnal hae-moglobinuria. Pulmonary emboli are treated with heparin and warfarin. Fibrinolytic drugs and acute embolectomy are used in certain situations. The differential diagnosis of sudden anxiety or a panic attack includes pulmonary embolus.
Sleep apnoea

Apnoea is deﬁ  ned as the complete cessation of respiratory airﬂ  ow 
for 10 or more seconds.(35) Apnoea can occur during any sleep 
stage, but is particularly likely to occur during the period of rapid eye movement sleep. It is important to remember that normal peo-ple have apnoeic episodes during sleep. When apnoeic events are frequent and prolonged, they lead to chronically disrupted sleep and excessive daytime somnolence. This deﬁ  nes the condition

known as sleep apnoea. Sleep apnoea can be central, obstructive, or a mixture of the two. Central sleep apnoea is caused by an abnor-mal central drive to the respiratory muscles. Congestive heart fail-ure is the most common cause, followed by neurological disorders involving the brainstem and respiratory centres. Obstructive sleep apnoea is more common; obesity is a major risk factor, but is not always present. Aside from disrupted sleep and daytime somno-lence, associated symptoms include an inability to concentrate, depressed mood, irritability, and personality changes. The sleeping 
partner often sleeps in another room because of the individual’s 
very loud snoring, snorting, gasping, and restlessness. Treatment with continuous positive airway pressure is often effective. Patients should avoid sedatives and alcohol. If obese, they should lose weight.
Gastrointestinal disorders
Oesophageal dysmotility

Oesophageal dysmotility can be demonstrated in 30 per cent of patients with non-cardiac chest pain;
(36) a signiﬁ  cant number of 
non-cardiac chest pain patients lack any evidence of oesophageal reﬂ ux and have reduced perception thresholds for pain. Cases of 
oesophageal dysmotility often lead to psychiatric consultation. Situational stress has not been conclusively linked to oesophageal dysmotility, but major psychiatric illness has.
(37) The majority of 
patients with oesophageal motility disorders have an Axis I psychi-atric illness, especially major depressive disorder (52 per cent), generalized anxiety disorder (36 per cent), somatization disorder (20 per cent), and substance-related disorders (20 per cent).
(38)

(38)
Smooth muscle relaxants, such as calcium-channel blockers, are superior to psychiatric treatments in improving physiological measures (such as oesophageal motility testing), antidepressants, and behavioural therapies produce more impressive changes in patients’ subjective oesophageal complaints and level of psycho-logical well-being.
(39)Irritable bowel syndrome
Irritable bowel syndrome (IBS) ranks second only to the common cold as a cause of absenteeism from work,
(40, 41) affecting between 
8 and 17 per cent of the general population in the United States.(40)

Symptoms include abdominal pain (relieved by defecation), and various forms of disturbed defecation such as altered stool fre-quency, altered stool form, altered stool passage, passage of mucus, and bloating. Symptoms must be continuous or recur within 3 months to meet the criteria for a diagnosis of irritable bowel syn-drome. The severity of this syndrome frequently correlates with periods of emotional stress; the sympathetic nervous system inhib-its gastric motility.
The enteric nervous system contains approximately 100 million 
neurons, close to the same number found in the spinal cord,
(41) and

(41) and 
more than those distributed to any other organ or physiological sys-tem. It therefore, makes sense that the gastrointestinal tract is uniquely sensitive to the neurophysiological aspects of the stress response. With IBS who seek medical care exhibit high rates of psy-chiatric disorders. The most frequently occurring are panic disorder (26 per cent), generalized anxiety disorder (26 per cent), social pho-bia (26 per cent), and major depressive disorder (23 per cent).
(42)
Patients with irritable bowel syndrome who are depressed and com-plain of diarrhoea may beneﬁ  t from tricyclic antidepressant treat-
ment, at least partially because of their anticholinergic effects. Anxious patients may also beneﬁ  t from, and well-tolerate buspirone. 
At least one in eight IBS patients are offered an antidepressant,
(43)

(43)
though data suggest that antidepressants are more consistent in improving global measures than speciﬁ  c gastrointestinal symptoms. 
A group of patients with treatment-refractory irritable bowel syn-drome—nearly half had no psychiatric disorder—more than 90 per cent beneﬁ  ted from low-dose antidepressant or antianxiety medica-
tions: 92 per cent of patients improved, and 56 per cent experienced complete remission of irritable bowel symptoms.
Inﬂ ammatory bowel disease
Inﬂ ammatory bowel disease is the collective term for patients who 
have ulcerative colitis or Crohn’s disease. The aetiology of inﬂ  am-
matory bowel disease is unknown, but it may involve immunologi-cal, infectious, or environmental factors.
(44) The primary manifes-

tations of acute ulcerative colitis are rectal bleeding, diarrhoea, urgency, fever, weight loss, and, sometimes, abdominal pain. Crohn’s disease presents with malaise, fever, abdominal pain, and frequently rectal bleeding. Surgical treatment (colectomy) cures ulcerative colitis but not Crohn’s disease. However, surgery is usu-ally a last resort in ulcerative colitis.
Despite the strong beliefs of early psychosomatic theorists, 
there is no objective evidence that psychiatric disorders cause inﬂ ammatory bowel disease. However, patients with this disease 
and who have psychiatric disorders are more likely to have unex-plained physical symptoms in other organ systems, more disability than patients with similar disease severity and no psychiatric disor-der, and prior histories of physical and sexual abuse.
(45)

(45)
Exacerbations of inﬂ  ammatory bowel disease symptoms are posi-
tively associated with major life events and major stressors.(41,46)
Stress-induced alterations in gastrointestinal inﬂ  ammation may be 
mediated through changes in hypothalamic–pituitary–adrenal axis function and alterations in bacterial-mucosal interactions, and via mucosal mast cells and mediators such as corticotrophin releasing factor.
(47) Treatment focuses on the identiﬁ  cation and treatment of 5.3.4 medical conditions associated with psychiatric disorder

SECTION 5  psychiatry and medicine 1084
psychiatric disorders, if found, and on stress management and 
quality of life issues. Walker et al.(44) treated inﬂ  ammatory bowel 
disease patients who had major depression with an antidepressant and found marked improvement in depression and ability to func-tion. Relaxation, stress management,
(45, 48) and hypnotherapy were 
found to reduce abdominal pain and diarrhoea.
Gastroesophageal reﬂ  ux and peptic ulcer disease
Acid reﬂ  ux and peptic ulcer disease are common causes of non-
cardiac chest pain.(49) Ulcer disease occurs when the balance 
between stomach acid and mucosal defence factors is disrupted. Gastric acid, Helicobacter pylori , and non-steroidal antiinﬂ  amma-
tory drugs are the most important risk factors in the development of peptic ulcers.
(50) The majority of patie nts with peptic ulcer disease

are present with epigastric pain that begins 1 to 3 h after eating. Treatment is aimed at reducing gastric acid (e.g. using cimetidine and ranitidine), improving mucosal defences (with, for instance, sucralfate), and/or eradicating H. pylori  (antibiotics).
On examination, at least half of the patients initially suspected of 
having peptic ulcer disease do not have evidence of an ulcer.
(51)
Among patients with non-ulcer dyspepsia, psychiatric comorbidity is high. Magni reported that 87 per cent of patients with non-ulcer dyspepsia have one or more anxiety disorders compared with 25 per cent of those with dyspepsia where there is endoscopic evidence of ulcer.
(52) Ang et al. reported that a majority of patients 
who have typical symptoms of gastroesophageal reﬂ  ux do not have 
erosions on examination; those patients with non-erosive reﬂ  ux

erosions on examination; those patients with non-erosive reﬂ  ux 
disease have a higher prevalence of psychiatric morbidity.(53)
Metabolic disorders
Obesity
Obesity is becoming an epidemic throughout the developed world. Existing standard treatments in university settings, only 20 per cent of obese patients lose around 9 kg (about 20 lbs) at 2-year follow-up and only 5 per cent of patients lose about 18 kg (40 lbs).
(54) The 
majority of people who lose weight on a diet gain it all back. Weight loss and weight maintenance after loss is associated with more ini-tial weight loss, reaching a self-determined goal weight, having a 
physically active lifestyle, a regular meal rhythm including break-
fast and healthier eating, control of overeating, and self-monitoring of behaviours.
(55) Associated with weight regain after signiﬁ  cant

(55) Associated with weight regain after signiﬁ  cant 
weight loss include a history of weight cycling, disinhibited eating, 
binge eating, more hunger, eating in response to negative emotions 
and stress, and more passive reactions to problems.
There is no ideal treatment for weight loss. Weight-loss pro-
grammes vary considerably in terms of risk, cost, and efﬁ  cacy. For 
most patients with mild to moderate obesity, a multidimensional approach is best, combining diet, exercise, behaviour modiﬁ  cation,

most patients with mild to moderate obesity, a multidimensional approach is best, combining diet, exercise, behaviour modiﬁ  cation, 
and social support. Motivated patients with morbid obesity (more than 100 per cent overdesired body weight) may be considered for very low calorie diets, with the emphasis on long-term diet, behav-ioural change, exercise, and social support. Increasingly, surgical approaches are being used; patient selection procedures have been developed to address motivations, psychological resilience, dietary education, potentially complicating psychiatric or substance-related factors, and ensuring patients are aware these procedures are not without risk—there are many structural and metabolic complica-tions, including death. It is important to treat comorbid psychiatric illnesses. It is associated with excessive intake of carbohydrate-rich 
foods and with resistance to engaging in physical activity.
(56)

(56)
With mood disorders and schizophrenia have a high prevalence of risk factors for cardiovascular disease, diabetes, and obesity, which are on the order of 1.5 to 2.5 times higher than in the general population.
(56) On the other hand, it is also important to be mind-
ful of metabolic effects of psychopharmacological agents, especially second generation antidepressants. The latter are associated with weight gain, dyslipidemia, and abnormal glucose homeostasis, especially with olanzapine.
(56)
Wilson’s disease
Wilson’s disease, or hepatolenticular degeneration, is an autosomal recessive disorder affecting between one and three persons per 100 000 of the population. The abnormality in Wilson’s disease is defective hepatic excretion of copper. The consequence is copper deposition and injury to many organs, particularly the liver and the brain, including diffuse white matter lesions seen on MRI in many patients.

(57) The genetic defect occurs on chromosome 13, and the 
gene product is probably a transmembrane copper transporter.(58)
Because copper accumulation is slow, signs and symptoms do not appear before the age of 6 years. Most patients present with mani-festations of organ damage between the ages of 8 and 20. Prolonged extrahepatic release of copper not bound to ceruloplasmin causes basal ganglion destruction, and sometimes cerebral cortex destruc-tion. Prominent neuropsychiatric symptoms include irritability, aggression, disinhibition, and recklessness. Depressive features are also common. The severity of psychiatric symptoms correlates with the severity of neurological symptoms, especially dystonic and bulbar manifestations.
(58)
Disorders of lipid metabolism

(58)
Intervention studies have shown that cholesterol reduction using diet, drugs, or surgery reduces the risk of developing or worsening coronary disease. In general, a 1 per cent reduction in low-density lipoprotein-cholesterol has been associated with roughly a 2 per cent reduction in disease end-points.
(59) General agreement exists 
that eating less saturated fat and cholesterol, and adopting a diet and exercise habits to reduce obesity will beneﬁ  t the health of most 
people. Exercise has a much greater effect in reducing triglyceride levels than in reducing low-density lipoprotein-cholesterol concen-trations. Triglyceride levels are reduced after even a single exercise session. The efﬁ  cacy of regular aerobic exercise in mild to moderate 
hypertriglyceridaemia has been repeatedly demonstrated.
(60)
Hepatic encephalopathy

(60)
The pathogenesis of hepatic encephalopathy is related to wide-spread hepatic necrosis, commonly due to an acute viral infection, such as hepatitis B, or exposure to hepatotoxins. Common hepato-toxins that lead to liver failure include acetaminophen, isoniazid, halothane, valproic acid, mushroom toxin, and carbon tetrachlo-ride. Hepatic encephalopathy that accompanies acute fulminant liver failure is frequently associated with cerebral oedema, which might be reversible and a treatable factor. Oedema is the leading cause of death in acute hepatic failure. It may respond to the administration of mannitol and measures to control agitation.
(61)
For patients with acute hepatic failure who have signiﬁ  cant hepatic 
encephalopathy, liver transplantation increases survival from 20 to 80 per cent, making rapid and accurate diagnosis vital. Survival of

1085
liver transplant patients with neuropsychiatric involvement is sig-
niﬁ cantly lower if there is liver disease alone.(61) There is also an 
increased incidence of liver disease among patients with primary psychiatric disorders, including substance use disorders.
(62) B virus 
carriers are almost three times more likely to have psychiatric dis-
orders than comparison subjects.(63)
Endocrine disorders
Type I diabetes (insulin-dependent diabetes mellitus) occurs when the pancreas’ ability to secrete insulin is clinically impaired. Hyperglycaemic symptoms emerge when 80 to 90 per cent of islet cells fail to produce insulin. Around 90 per cent of diabetics have type II diabetes (non-insulin-dependent diabetes mellitus). Type II 
diabetes is characterized by peripheral resistance to the action of

diabetes is characterized by peripheral resistance to the action of 
insulin and decreased insulin secretion, in spite of the presence of elevated serum glucose levels. Patients with type II diabetes can often avoid or postpone the need for insulin treatment with appro-priate diet and exercise. Both type I and II diabetes are associated with a genetic predisposition.
(64)
The most frequent psychiatric disorders in patients with diabetes 
are anxiety and depressive disorders. Among general populations of diabetics, anxiety disorders occurred in up to 45 per cent and depressive disorders in up to 33 per cent.
(65) Rosenthal et al.(66) in a

(65) Rosenthal et al.(66) in a 
3-year prospective study of hospitalizations and mortality in older patients with diabetes, found that the combined presence of retin-opathy and a high depression score on the Geriatric Depression scale had the strongest relationship with mortality. Patients with diabetes are twice as likely to experience depression as those without diabetes; this holds true for both type I and II diabetes.
(66) Patients 
with schizophrenia are at increased risk for developing type II dia-betes
(67) is growing interest in the possibility that there are shared 
inherited risk factors for the two disorders,(68) though the evidence 
is weak and largely circumstantial. In addition, second generation antipsychotic medications, especially olanzapine, are associated with type II diabetes mellitus and abnormal glucose metabolism.
Diabetic patients who have psychiatric disorders can have less

Diabetic patients who have psychiatric disorders can have less 
disease morbidity when their psychiatric disorders are appropri-ately treated, highlighting the importance of monitoring diabetic patients for psychiatric disorders and monitoring psychiatric patients for excess weight and diabetes.
(69) Independent of the level 
of physical illness present in type I or II diabetes, the presence of anxiety and/or depression is important in determining the quality of a patient’s life.
(70) Treatment adherence problems complicate 
care, particularly in children and adolescents with type I diabetes. A great deal of patience, family support, and education is necessary to minimize passive and active non-compliance.
Hypothyroidism

Hypothyroidism is usually the result of primary failure or ablation of the thyroid gland, hypothalamic dysfunction, pituitary dysfunc-tion, autoimmune thyroiditis, or lithium therapy. Clinical manifes-tations of hypothyroidism include fatigue, cold intolerance, lethargy, weakness, weight gain, constipation, menstrual irregulari-ties, hair loss, slow reaction time, oedema, delayed reﬂ  exes, and 
bradycardia. Hypothyroidism occurs in as many as 10 per cent of patients taking lithium; lithium-induced hypothyroidism is more likely to occur in women.
(70)The association between clinical hypothyroidism and depression 
is well known. Gold et al .(71) found that 5 per cent of a series of

is well known. Gold et al .(71) found that 5 per cent of a series of 
250 patients with major depressive syndromes had at least subclin-ical hypothyroidism. In many patients with hypothyroidism, the depression responds to thyroid hormone replacement alone,
(72)
but the response may take a long time. When that is the case, anti-depressants are indicated and efﬁ  cacious.
(71)
Hyperthyroidism
The most frequent clinical manifestations of hyperthyroidism are 
nervousness, diaphoresis, hypersensitivity to heat, palpitations, fatigue, weight loss, tachycardia, dyspnoea, and weakness. The most common causes include Graves’ disease, toxic adenoma, and toxic multinodular goitre. Less common causes include Hashimoto’s thyroiditis, postpartum hyperthyroidism, and factitious hyperthy-roid state.
As with hypothyroidism, depressive and anxiety syndromes are

As with hypothyroidism, depressive and anxiety syndromes are 
the most common psychiatric conditions seen among patients with hyperthyroid states; there is a three-fold increased risk for develop-ment of mood disorder following hospitalization with hyperthy-roidism.
(73,74) When patients have depressive or anxiety syndromes 
in the context of hyperthyroidism, and have no past histories of psychiatric disorders, the psychiatric symptoms resolve more than 90 per cent of the time when the hyperthyroidism resolves. This obviates the need for other psychiatric interventions unless antithy-roid medication, radioactive iodine, or thyroid surgery has not been successful.
(74) Anxiety symptoms will disappear in direct rela-
tion to the reduction of thyroid hormone levels. Depressive symp-toms are not quite so linearly related and may resolve at a slower pace as thyroid hormone level normalize.
Hypoparathyroidism

Parathyroid hormone mobilizes calcium from bone, induces renal reabsorption of calcium, increases renal clearance of inorganic phosphate, and promotes intestinal reabsorption of calcium. Hypoparathyroidism would be expected to result in hypocalcae-mia, which can cause delirium. Hypoparathyroidism can result from autoimmune destruction of the parathyroid glands, removal of the parathyroids, disruption of the glands’ blood supply, tumour, or neck irradiation. Medical and neuropsychiatric symptoms and signs are related to the level of serum calcium and the rate at which hypocalcaemia develops. Faster the hypocalcaemia develops, the more likely delirium and other neuropsychiatric symptoms are to occur. The most frequent symptoms are caused by neuromuscular irritability and include paraesthesias, carpal pedal spasm, laryngos-pasm, blepharospasm, and bronchospasm.
(75) Cardiovascular

(75) Cardiovascular 
manifestations include prolonged Q–T interval, heart block, and congestive heart failure. The most common neuropsychiatric symptoms and signs are seizures, EEG abnormalities, increased intracranial pressure, disorientation, confusion, and extrapyrami-dal symptoms. The mainstays of treatment are calcium and vita-min D. Neuropsychiatric syndromes should resolve with the nor-malization of serum calcium.
Hyperparathyroidism
Typically, hypercalcaemia is discovered by routine laboratory test-ing in patients without obvious illness. Primary hyperparathy-roidism is the most common cause of hypercalcaemia among adult patients; among hospitalized patients, malignancy is the most 5.3.4 medical conditions associated with psychiatric disorder

SECTION 5  psychiatry and medicine 1086
 common cause.(75) Reversible hyperparathyroidism and hypercal-
caemia are also associated with lithium therapy.(76) In primary 
hyperparathyroidism, parathyroid hormone is secreted inappropri-ately, despite an elevation in the ionized calcium level. Signs and symptoms of hyperparathyroidism include nausea, vomiting, ano-rexia, constipation, proximal muscle weakness, polyuria, polydipsia, impaired renal function, hypertension, short Q–T interval, brady-cardia, and a number of neuropsychiatric symptoms. The latter include lethargy, drowsiness, impaired concentration ability, and confusion. In severe cases, there may be stupor or coma, psychosis, and cognitive impairment are common in patients who have serum calcium levels above 16 mg/dl. Depressive symptoms, but not cog-nitive symptoms, tend to resolve with treatment.
(77) Cognitive 
symptoms may improve, but residual symptoms usually remain.
Cushing’s syndrome

Hypersecretion of cortisol by the adrenal gland can result in Cushing’s syndrome. Cushing’s syndrome can also be due to exog-enous ACTH or glucocorticoid administration, or endogenous hyperproduction of these hormones. Because a physiological release of cortisol occurs during periods of stress or duress, it is common to see elevations of serum cortisol during the courses of many psychiatric disorders, including major depressive disorder, alcoholism, anorexia nervosa, panic disorder, and psychoactive substance-withdrawal syndromes. The more common clinical signs and symptoms of Cushing’s syndrome, whether endogenous or exogenous, include fat redistribution, menstrual irregularities, dys-phoria, thin skin, moon facies, increased appetite, sleep disturbances, hypertension, hypercholesterolaemia, hypertriglyceridaemia, poor concentration, impaired memory, euphoria, glucose intolerance,

striae, and hirsutism.
At least half of all patients with Cushing’s syndrome will experience 
depressive or manic symptoms
(78); the symptoms will be moderate to 
severe in half of these patients. Many will also experience psychotic symptoms. Symptoms are dose-related when due to exogenous ster-oids. Depression or mania due to Cushing’s syndrome will eventually remit when the hypercortisolaemia is corrected, the return to euthymia is usually gradual. When depression or mania is slow to remit, treat-ment with antidepressants or mood stabilizers is warranted.
Addison’s disease
Addison’s disease is the result of an autoimmune process that destroys the adrenal glands; it is the most common cause of primary adrenal insufﬁ  ciency in the industrialized world, accounting 
for about 65 per cent of cases.
(70) Both glucocorticoid and mineralo-
corticoid secretion are diminished in this condition. Clinicalmanifestations of adrenal insufﬁ  ciency include weight loss, fatigue,

corticoid secretion are diminished in this condition. Clinicalmanifestations of adrenal insufﬁ  ciency include weight loss, fatigue, 
vomiting, diarrhoea, anorexia, and salt-craving. Patients with Addison’s disease will require lifelong replacement of both glucocor-ticoids and mineralocorticoids. Patients may be misdiagnosed with major depressive disorder, personality disorder, dementia, or somato-form disorders. It is not uncommon for the diagnosis to be delayed for many months; Addison’s disease is a disorder to be continually mindful about in a patient with treatment-resistant depression.
Hyperprolactinaemia
Prolactin is synthesized in the pituitary gland; its secretion is increased during pregnancy, enhancing breast development. Prolactin secretion is inhibited by glucocorticoids and thyroid hor-
mone, it is predominantly under the inhibitory control of dopamine.
(70) Dopamine is, in fact, prolactin inhibiting factor. This

(70) Dopamine is, in fact, prolactin inhibiting factor. This 
is why dopamine blocking medications such as neuroleptics can 
cause hyperprolactinaemia. Symptoms of hyperprolactinaemia include breast development and lactation. These bothersome side effects of neuroleptics, particularly in men, can be modulated by changing to a more favourable neuroleptic medication, such as a second generation antipsychotic.
Hypopituitarism
Hypopituitarism occurs when multiple pituitary hormones exhibit decreased secretion. It can be due to either gland destruction or inadequate stimulation by factors that regulate pituitary function-ing. Common causes of hypopituitarism are pituitary adenomas, hypothalamic tumours, metastatic carcinoma (especially breast and bronchus), and cerebral trauma and haemorrhage.
(70) Other

(70) Other 
causes include vascular disorders, immunological conditions, and a variety of congenital anomalies. Clinical manifestations depend on which hormones are deﬁ  cient; signs and symptoms are those of the 
individual deﬁ  ciency states. Other signs that may be present when 
there is hypopituitarism include headache, visual loss, and radio-graphically discovered sella enlargement. Treatment of patients with hypopituitarism involves hormone replacement therapy and surgery when accessible lesions are present.
(70)
Autoimmune disorders
Systemic lupus erythematosus
Systemic lupus erythematosus is characterized by the production of autoantibodies that injure tissue in several organ systems, most frequently the skin, central nervous system, kidney, and lungs. In addition, non-speciﬁ  c symptoms occur in a large majority of 
patients, including fatigue, fever, weight loss, arthralgias, and myal-gias.
(79) The most common presenting symptoms are fever, arthral-

gias, butterﬂ  y rash, photosensitivity, Raynaud’s phenomenon, and 
mucous ulcers. The laboratory diagnostic hallmark of systemic lupus erythematosus is the production of high-titre autoantibodies directed against a variety of cell nucleus components (antinuclear 
antibodies). Systemic lupus erythematosus has no known cure, so treatment is based on symptom relief, suppression of inﬂ  amma-
tion, and preventing future pathology.
The most common psychiatric presentations of active systemic 
lupus erythematosus are psychosis, delirium, seizures, and cognitive 
(80) Autoantibodies to neuronal membranes, which 
interfere with the ability of neurones to respond to stimuli, may account for most neuropsychiatric deﬁ  cits and symptoms,
(81)
though CNS vasculitis during the course of this disease may also

(81)
though CNS vasculitis during the course of this disease may also 
play a role in some patients. Symptoms in lupus patients are likely to be related to unique sets of autoantigens,
(82) and are related to 
antibodies against N-methyl- D-aspartate (NMDA) receptors.(83)
Antibodies may be partially responsible for depression, short-term 
memory problems, and new learning difﬁ  culties in lupus patients. 
Signiﬁ  cantly associated with declining cognitive function are con-
sistently positive antiphospholipid antibodies, consistent steroid use, diabetes, and higher depression scores.
(83) Mood syndromes 
are probably the most common psychiatric presentation of patients with systemic lupus erythematosus,
(84) but mood change is not

1087
always due to involvement of the central nervous system. Patients 
are frequently treated with steroids, which raise the possibility of steroid-induced neuropsychiatric syndromes. However, in many cases, addition of steroids to treatment may improve psychiatric syndromes.
Renal disorders
Acute renal failure
Acute renal failure is an abrupt decrease in renal function sufﬁ  cient 
to result in azotaemia—retention of nitrogenous waste in the body.
(85) Acute renal failure can result from a decrease of renal 
blood ﬂ  ow (prerenal azotaemia), intrinsic renal disease (renal azo-

taemia), or obstruction of urine flow (postrenal azotaemia). Prerenal azotaemia can be caused by renal arterial occlusion or a decrease in the effective blood volume (e.g. haemorrhage, conges-tive heart failure, diarrhoea). Intrinsic renal azotaemia is most commonly caused by acute tubular necrosis due to an acute ischae-mic or nephrotoxic insult. Azotaemia is due to obstruction of the urine collecting system; this may occur when there is bladder outlet obstruction or ureteral obstruction.
Medical complications of acute renal failure include hyperkalae-
mia, hyperuricaemia, arrhythmias, anaemia, coagulopathies, vom-iting, nausea, and urinary tract infections. Metabolic perturbations can lead to delirium. Neuropsychiatric manifestations include

mia, hyperuricaemia, arrhythmias, anaemia, coagulopathies, vom-iting, nausea, and urinary tract infections. Metabolic perturbations can lead to delirium. Neuropsychiatric manifestations include 
somnolence, asterixis (ﬂ  apping tremor), neuromuscular irritability, 
and seizures. Mental status abnormalities in acute (but not chron-ic) renal failure begin to occur for most adults when the serumcreatinine level acutely rises to about 4.0 mg/dl. In oliguric renal failure, serum blood urea nitrogen levels can be expected to rise by about 10 to 20 mg/dl per day. Serum creatinine levels can be expected to rise by about 1 mg/dl per day. Neuropsychiatric complications of acute renal failure are best treated by correcting the underlying cause of the renal failure. Dialysis may be used to manage acute 
manifestations. While awaiting reversal of neuropsychiatric mani-
festations, symptomatic management with antiseizure medications 
and neuroleptics may be necessary.

Chronic renal failure and end stage renal disease
Chronic renal failure is a progressive and irreversible loss of renal 
function.(86) The most common aetiologies of renal insufﬁ  ciency 
ultimately leading to end stage renal disease are diabetes, hyperten-sion, and glomerulonephritis. Loss of up to 75 per cent of glomeru-lar ﬁ ltration rate does not usually result in pronounced clinical 
symptoms, as the remaining glomeruli adapt with hyperﬁ  ltration. 
Serum creatinine is a sensitive indicator of early, subclinical, chron-ic renal failure. For example, the doubling of serum creatinine from 0.7 to 1.4 mg/dl signiﬁ  es a loss of approximately 50 per cent of 
glomerular ﬁ  ltration rate, emphasizing the importance of early 
detection and prevention.
Patients with chronic renal failure usually become symptomatic

Patients with chronic renal failure usually become symptomatic 
when glomerular ﬁ  ltration rate is less than 10 ml/min. Uraemia 
affects every organ system, including the central nervous system. Neuropsychiatric manifestations of chronic renal failure include 
irritability, insomnia, lethargy, anorexia, seizures, and restless legs 
syndrome.
(86) In contrast to acute renal failure—where neuropsy-
chiatric signs and symptoms may appear with a creatinine level as low as 4 mg/dl—in chronic renal failure, patients may have a normal mental status examination with a serum creatinine level 
as high as 9 to 10 mg/dl. Symptomatic treatments with low-dose neuroleptics, antiseizure medications, or benzodiazepines are sometimes necessary in chronic renal failure.
Kimmel et al .
(86) studied the prevalence of hospitalizations for

(86) studied the prevalence of hospitalizations for 
psychiatric illness in patients with end stage renal disease and com-pared that rate with four other chronic medical conditions (diabe-tes, ischaemic heart disease, cerebrovascular disease, and peptic ulcer disease). Hospitalizations for mental disorders were 1.5 to 3.0 times higher in these patients than in patients with the four other chronic diseases. Dementias and depression were the most common reasons for hospitalization. With end stage renal disease are almost twice as likely to die by suicides as the general popula-tions, after controlling for other potential demographic and clini-cal contributors to suicide risk.
(87)
Sexual dysfunction is very common in patients with end stage 
renal disease. Abrams et al.(88) found that 75 per cent of his sample

(87)
renal disease. Abrams et al.(88) found that 75 per cent of his sample 
of men with this disease reported a decrease in frequency of sexual intercourse of at least 50 per cent. Disruptions in sexual function, which may be physiological (e.g. vascular complications of diabe-tes, fatigue following dialysis treatments) or psychological or both, account for at least a portion of the dysphoria experienced by patients with end stage renal disease.
The deﬁ  nitive treatments for most patients with chronic renal 
failure are transplantation or haemodialysis. In general, transplan-tation is encouraged because of a better quality of life and a greater chance for rehabilitation and symptom resolution. Researchers in three separate prospective studies found that patients who received renal transplants experienced better physical and psychological outcomes than patients who remained on dialysis.
(89)

(89)
Neuropsychiatric signs and symptoms resolve much more com-pletely with transplantation than with haemodialysis. Psychiatric aspects of organ transplantation are discussed later. The psychiatric aspects of haemodialysis are discussed next.
Haemodialysis
The average patient on haemodialysis requires 3.5 h of dialysis three times per week to achieve adequate creatinine clearance.
(86)
Haemodialysis has enabled the survival of countless thousands of patients with chronic renal failure and provides a temporary man-agement tool for patients on transplantation waiting lists. However, it is not a benign procedure, and has a number of potential neuropsy-chiatric complications. Patients on haemodialysis are at high risk for developing volume overload, pulmonary oedema, hyperkalaemia, hyperphosphataemia, and metabolic bone disease if compliance with restricted diet and ﬂ  uid intake is not optimal. Patient adherence to

these diet and ﬂ  uid-intake protocols are used as one of the criteria for 
making decisions about appropriateness for transplantation. Psychiatric reasons for non-adherence should be addressed and are usually reversible, with the exception of personality disorders. These include mood disorders, phobias, panic disorder, substance-related 
disorders, adjustment disorder, and cognitive disorders.
Haematological disorders
Anaemia due to vitamin deﬁ  ciency
Both folic acid and cobalamin (vitamin B12) are necessary for the 
production of DNA; in their absence, the nucleus of the cell cannot 5.3.4 medical conditions associated with psychiatric disorder

SECTION 5  psychiatry and medicine 1088
undergo normal mitosis. The main cause of folic acid deﬁ  ciency is 
dietary insufﬁ  ciency.(90) This commonly occurs in severe alcohol-
ics. The main cause of cobalamin deﬁ  ciency is malabsorption. The 
major clinical manifestations of folate or vitamin B12 deﬁ  ciency 
include fatigue, pallor, and for cobalamin deﬁ  ciency, neuropsychi-
atric manifestations. The latter include loss of proprioception in 
the lower extremities, loss of vibratory perception, anosmial, for-getfulness, and even dementia. Diagnosis is based on measurement of serum levels of vitamin B12 and folate. Treatment is replacement of folate (1 mg/day or improved diet) and vitamin B12 (adminis-tered parenterally).
In cobalamin deﬁ  ciency, neuropsychiatric ﬁ  ndings can occur 
even when megaloblasts and anaemia are absent.
(91) Patients with

(91) Patients with 
cobalamin levels between 100 and 200 pg/ml, and especially those with levels less than 100 pg/ml, may have cobalamin-reversible neuropsychiatric deﬁ  cits.
(138) Even dementia due to chronic cobala-
min deﬁ  ciency may be partially reversible when diagnosed and 
aggressively treated. It is also associated with a higher risk of depres-sion, especially in older adults; anaemia severity and depression severity scores are highly correlated.
(92) Treatment of the anaemia 
may result in resolution of depressive symptoms; in some cases depressive symptoms are slower to resolve and may require extended treatment with antidepressant medication, particularly for patients predisposed to mood disorders.
Iron-deﬁ  ciency anaemia
When erythrocyte-cytoplasm production is abnormally low due to

When erythrocyte-cytoplasm production is abnormally low due to 
the reduced production or availability of one of the three compo-nents of haemoglobin (iron, globin, or haem), the ratio of cyto-plasm to the contents of the rest of the cell declines. This results in a microcytic anaemia. In most cases, microcytic anaemia is due to iron-deﬁ  cient haemopoiesis.
(92) Deﬁ  ciency is usually due to an 
iron-poor diet or defective iron utilization by the body. Clinical manifestations of iron-deﬁ  ciency anaemia are related to the severity 
of the iron deﬁ  ciency and include severe fatigue, pallor, changes in 
nail curvature (‘spoon nails’), and, at times, pica and cheilosis at the corners of the mouth. A diminished haematocrit and mean cor-puscular volume, and low serum iron are the cornerstones of the diagnosis. The severe fatigue associated with iron deﬁ  ciency can be

misdiagnosed as major depressive disorder; treatment with an anti-depressant will not help unless there is also clinical major depres-sion apart from the iron deﬁ  ciency. Iron replenishment to correct 
the underlying deﬁ  ciency is the speciﬁ  c. With iron replenishment, 
the haemoglobin should correct to normal, and symptoms should resolve, within 4 to 6 weeks.

There is increasing recognition that patients with psychiatric signs and symptoms frequently have associated medical disorders. Interactions between the disorders can be quite complex and may involve neuropsychiatric manifestations of medical illness, medical effects of psychiatric treatments, psychiatric effects of medical treatment, increased medical illness related to factors inherent in the psychiatric condition, and maladaptive personality styles or disorders that affect outcomes of medical and psychiatric illness. Psychiatric disorders in patients with other medical illnesses increase mortality, morbidity, health care costs, and decrease adherence to medical therapies. Appropriate and cost-effective management must integrate knowledge from psychiatry and pri-

mary care to assure maximal therapeutic gains for the patient. Those involved in consultation to primary care providers must understand both the basic pathophysiology and clinical character-istics of the medical disorders and their treatments, as well as pos-
sess the psychiatric knowledge necessary to ensure that the patient 
with medical illness is adequately managed.
Robinson, M.J. and Owen, J.A. (2005). Psychopharmacology. In Textbook 
of psychosomatic medicine  (ed. J.L. Levenson), pp. 871–3. American 
Psychiatric Publishing, Inc., Washington, DC.
Saha, S., Chant, D., and McGrath, J. (2007). A systematic review of mortality 
in schizophrenia. Archives of General Psychiatry ,64, 1123–31.
Schmitz, N., Thefeld, W., and Kruse, J. (2006). Mental disorders and 
hypertension: factors associated with awareness and treatment of hypertension in the general population of Germany. Psychosomatic 
Medicine ,68, 246–52.

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5.3.5 Psychiatric aspects 
of infections

Neuropsychiatric disturbances stemming from infectious diseases 
are widespread in both the industrialized world and developing countries. Such neuropsychiatric syndromes are not necessarily the result of infectious processes directly involving the central nervous system, they may also be complications of systemic infections. There are many microbial, viral, and parasitic agents, as well as other types of infectious substances, which can affect the central nervous system, leading to the appearance of neurological and psy-chiatric symptoms that may cause suffering to the patient, and even be disabling.
When considering the psychiatric manifestations of infectious 
illness, it is important to consider clinical manifestations derived

1091
from a possible systemic infection, which can be less obvious 
than a direct involvement of the central nervous system. Acute organic reactions may accompany many systemic infections, especially at the extremes of life. A clear example is the delirium that frequently occurs with pneumonia in the elderly. In these clinical syndromes, several factors could be responsible for the alterations in cerebral metabolism. The mere fact of having a fever could be involved. Cerebral anoxia often appears to be responsible, or the inﬂ  uence of toxins derived from the infecting 
micro-organism. More complex metabolic disturbances or the accumulation of toxic intermediate products can also be  implicated.
Likewise, infections that course as chronic or subacute illnesses

Likewise, infections that course as chronic or subacute illnesses 
are frequently accompanied by the onset of depressive syndromes. One of the factors implied in clinical depression that occurs within the context of systemic infectious illnesses (e.g. tuberculosis and infectious mononucleosis), is a sense of physical vulnerability, possibly heightened by a loss of strength and negative changes in the patient’s appearance. Patients are often afraid of losing their earning capacity or even their jobs, as well as other social and occu-pational problems associated with the illness.
Another very important factor, above all with the human immu-
nodeﬁ  ciency virus ( HIV ) and other sexually transmitted disease 
(STD ), is the social stigma that these patients may suffer.
(1) Sexually

(1) Sexually 
transmitted disease infection implies sexual activity that histori-cally carries connotations of illicit, casual, sexual encounters, and acquiring an STD is frequently associated with embarrassment and social stigma.
In addition to the disease itself, the medications commonly used 
to treat infectious illnesses can have side-effects that alter patients’ behaviour, as well as their cognitive and affective functioning(Table 5.3.5.1).
In this chapter we consider infections of clinical interest in the 
practice of psychiatry. These conditions will be dealt with brieﬂ  y, 
and textbooks of general medicine should be consulted for further details. Prion diseases and chronic fatigue syndromes, which are also related to the subject of the present chapter, are discussed in Chapters 4.1.4 and 5.2.7, respectively.
HIV infection

Patients infected with HIV are at an increased risk for a variety of mental disorders. Those encountered most frequently in psychiat-ric practice are discussed below. HIV dementia is discussed in Chapter 4.1.9.
Nature of neuropsychiatric disorders in HIV-infected 
patients
Neuropsychiatric disorders are common in HIV-infected patients, 
and they can be either primary or secondary. Primary  complica-
tions are those that can be attributed directly to the infection of the central nervous system by the virus, or to immunopathological events precipitated by HIV infection. Primary HIV-related brain disorders include HIV-related dementia and minor cognitive disorder.
(2) Immune suppression can lead to a variety of secondary 
complications affecting the brain, including opportunistic infec-tions (e.g. cerebral toxoplasmosis and progressive multifocal leuco-
encephalopathy) and tumours (e.g. cerebral lymphoma). Secondary

complications in the form of acute and subacute syndromes (e.g. delirium) often occur as a result of cerebrovascular complications 
and toxic states induced by various therapeutic agents.
HIV-associated acute stress reaction
This transitory syndrome appears in some individuals after they are notiﬁ  ed of their seropositivity. It is equally frequent among 
those who, after a period as an asymptomatic carrier, are informed that the infection has progressed towards full-blown AIDS. The appearance of these symptoms is closely linked in time to the stressful circumstance, and generally remits in hours or days.
The symptoms are highly varied. Some patients suffer from 
intrusive thoughts or brooding related to their uncertainties regard ing

intrusive thoughts or brooding related to their uncertainties regard ing 
health, the future, the risk of contagion to others (especially loved ones), and the idea of death. The vegetative symptoms of panic attacks are also usually present. In more severe cases, the patient may also present social isolation, verbal expressions of rage or feelings of desperation, and other forms of altered behaviour.Table 5.3.5.1  Neuropsychiatric adverse effects of drugs frequently 
used in the treatment of infectious diseases
Drug Adverse effect
Aciclovir Headache, somnolence, tremor, confusion, lethargy, 
seizures, agitation, major depression with psychotic 
symptoms
Amphotericin B DeliriumChloramphenicol Memory impairment, confusion, depersonalization, 
hallucinations
Cycloserine Depression, anxiety, confusion, hallucinations, 
paranoia, agoraphobia

symptoms
Didanosine (ddl) Headache, asthenia, polyneuropathyEfavirenz Dizziness, headache, insomnia, inappropriate 
behaviour, depression, concentration impairment, 
agitation, abnormal dreaming, and somnolence
Foscarnet AstheniaGentamicin Confusion, hallucinationsInterferon Depression, anxiety, irritability, deliriumIsoniazid (INH) Headaches, vertigo, hyper-reﬂ  exia, neuritis, 
convulsions, ataxia, toxic, encephalopathy, confusion, 
psychosis, antidepressant effect
Ketoconazole Somnolence, deliriumPara-aminosalicylate 
(PAS)Toxic psychosis
Penicillin G (procaine) Hallucinations, seizures, agitation, confusion
Rifampicin (rifampin) Myopathy, headache if hypersensitivityStreptomycin Toxic effects on cranial nerve VIII (vestibular), vertigo, 
nystagmus, ataxia, neuromuscular junction blockade

Sulphonamide Anxiety, depression, insomnia, hallucinationsTrimethoprim-
sulphamethoxazoleVertigo and confusion
Zalcitabine (ddC) Polyneuropathy
Zidovudine (AZT) Headache, myalgia, insomnia, asthenia, somnolence, 
anxiety, depression, mania, restlessness5.3.5 psychiatric aspects of infections

SECTION 5  psychiatry and medicine 1092
Depression is one of the most common psychiatric disorders found 
among HIV-infected individuals. Symptomatic stages of HIV infec-tion are associated with an increased prevalence of depressive symptoms and a syndromal diagnosis of major depression.
(3)
There are several factors behind the increased morbidity for 
affective disorders found in this population. First of all, the patient’s discovery of the infection has a dramatic psychological impact , as 
does the disease’s relentless progression. Second, the neurotropism 
of the virus  itself produces neuropathological changes in deep grey

of the virus  itself produces neuropathological changes in deep grey 
structures whose dysfunction is known to cause mood disturbances and changes in the neurotransmission systems, which may contrib-ute to the development of depression. Finally, the groups that in Western countries are at the highest risk for HIV infection (intra-venous drug users and male homosexuals/bisexuals) are also known to be at a high risk for depressive syndromes , indepen-
dently of having the virus. The risk factors for depression appear to be similar to those for HIV-seronegative patients and include, b esides 
advanced HIV infection: loss of social support; personal and family history of depression; drug use; and lack of conﬁ  dants.
When severe physical disease is present the diagnosis of major 
depression can be difﬁ  cult to make, because the disease itself may

depression can be difﬁ  cult to make, because the disease itself may 
be the real source of many depressive symptoms, for example insomnia, loss of appetite and weight, fatigue, lack of energy, retar-dation, and concentration difﬁ  culties. T o avoid misdiagnosing 
depression, it is important to focus on the more psychological, as opposed to somatic, symptoms associated with low mood. These include persistent low mood ,loss of enjoyment  of usually 
pleasurable activities, suicidal thoughts  and marked feelings of 
hopelessness ,guilt , and self-reproach . Suicidal ideation may not 
be expressed directly, but may be expressed more passively, for example poor adherence to medical treatment. Assessment of depressed mood also requires evaluation of the probable contrib-uting factors.
(i) Pharmacological treatment

Antidepressants are the treatment of choice in major depression, as well as in less severe depressive syndromes that are unresponsive to psychological and social intervention. Tricyclic antidepressants have been shown to be effective in treating depressed HIV-positive patients.
(4) AIDS patients can respond to lower dosages of tricyclics 
(25–100 mg), but they may also suffer severe anticholinergic effects at reduced dosages. Therefore, the choice of an antidepressant for these patients should be guided by its side-effect proﬁ  le.
Several studies have been published showing therapeutic 
response to selective serotonin reuptake inhibitors in seropositive patients with major depression.
(5) Many clinicians prefer the newer 
drugs in the medically ill, not only because of their higher accep-tance among patients, but also because of their greater overdose safety margin.
(ii) Psychotherapy

Psychosocial interventions derived from a wide variety of theoreti-cal orientations are effective in treating depression among individ-uals infected with HIV . There is good evidence for the value of psychological intervention in the management of HIV patients. Both interpersonal psychotherapy
(6) and cognitive–behavioural group therapy(7) may be particularly beneﬁ  cial for HIV patients 
with depressive symptoms.
Psychosis
Psychotic disorders sometimes occur in people with HIV infection. While their prevalence is not high, such a development can lead to complicated diagnostic and management problems. The fact that psychosis can be related to HIV infection does not imply that a new disease entity or diagnostic category has been identiﬁ  ed. When

seropositive individuals present with psychotic symptoms, efforts should be made to clarify the clinical features and to establish their aetiology, which could well be unrelated to HIV . While in some cases the psychotic symptoms may be the result of subtle or gross brain pathology associated with HIV infection, in others it may be iatrogenic or secondary to substance misuse. Psychiatric patients per se may be considered a group at risk for contracting HIV infection.
(8)
Neuroleptics are the treatment of choice for controlling psycho-
tic symptoms. The risk of developing antipsychotic-induced extra-pyramidal symptoms is higher in psychotic patients with AIDS than in psychotic patients without AIDS. AIDS patients may have an increased risk of developing tardive dyskinesia, neuroleptic malignant syndrome, and severe dystonic reactions.
(9) The presence

(9) The presence 
of organic cerebral deterioration, in particular HIV-associated dementia, is a risk factor for the development of neuroleptic malig-nant syndrome. In general, when using neuroleptics in this popula-tion, the best course is to start off with low doses, and increase the dosage slowly and progressively. The new antipsychotic risperidone has been associated with fewer extrapyramidal side-effects and used successfully in this group of patients.
(10)
Mania
HIV seems to increase the risk of manic episodes, and mania is a frequent reason for psychiatric hospitalization among people with the virus.
(11) In some cases illicit drug use or iatrogenic causes are 
implicated, for example the chance association of HIV infection and bipolar affective disorders, but generally no obvious aetiologi-cal factors can be identiﬁ  ed. Mania has been found to be a side-

effect of medication frequently used for HIV/AIDS, including didanosine (ddl) ,ganciclovir ,procarbazine ,estavudine  (d4T), 
steroids, and zidovudine  (AZT ). Most cases of new-onset mania 
occur in advanced HIV disease and they are often associated with the presence of substantial cognitive impairment. New-onset mania in severe symptomatic disease is predictive of reduced survival.
Standard pharmacotherapy with neuroleptics and lithium are 
effective, but the usefulness of these drugs may be restricted by the development of severe adverse effects in immunosuppressed HIV-infected patients. Most psychiatrists choose atypical neuroleptics 
for HIV . However, these agents are not without risk for extrapyra-

midal side-effects in HIV patients, including the risk for metabolic inhibition of some agents by protease inhibitors. Potent antiretro-viral therapy has been documented to protect against the develop-ment of HIV-associated mania.
(12)
Delirium
Delirium is one of the organic mental disorders observed most fre-quently in hospitalized HIV-infected patients. The exact prevalence of delirium or acute organic brain syndrome in HIV is unknown.

1093
Patients with advanced systemic disease and dementia are at a high 
risk for delirium, the cause of which is often multifactorial. The precipitant organic factors involved are listed in Table 5.3.5.2.
A conservative attitude has been recommended for the manage-
ment of these conditions, with the use of low oral or intramuscular doses of neuroleptics, and correction of the organic disorders responsible for the development of disturbances in the level of con-sciousness.
(13) However, other authors have postulated that patients 
suffering from delirium and agitation should be given high doses of neuroleptics—alone or in combination with lorazepam—in cases where quick control of the symptoms is vital.
(14) The efﬁ  cacy of 
pharmacological interventions in patients with delirium is height-ened if treatment is begun as soon as the ﬁ  rst symptoms appear.
Other central nervous infections in HIV-related illness
In the advanced phases of AIDS, opportunistic infections are

In the advanced phases of AIDS, opportunistic infections are 
highly varied, as are the neoplasias that can develop in immunode-pressed individuals, which affect the central nervous system. The more frequents are:
◆ Progressive multifocal leucoencephalopathy .This is a grave 
neurological complication, linked to papovavirus infection. Dementia can develop rapidly, with focal neurological altera-tions such as blindness, ataxia, and hemiparesia. Death follows very quickly thereafter, and there is no known treatment. Computerized brain images taken from these patients show a characteristic involvement of the white matter .
◆ Cerebral toxoplasmosis.  It is linked to the reactivation of a latent 
cerebral infection by  Toxoplasma gondii, an opportunistic intra-

cellular protozoan. The clinical presentation can vary greatly, but it is characterized by the rapid development of a marked altera-tion in the mental state. The focal involvement can produce headache and lateralized neurological effects. The lesions tend to be located in basal ganglia. Diagnosis is based on structural neu-roimaging tests, and treatment is with pyrimethamine and sulphadiazine .
◆ Cryptococcal meningitis (torulosis).  This form of meningitis, 
caused by infestation with the yeast-like fungus  Cryptococcus 
neoformans, is characterized by headache, meningism (although 
it sometimes courses without this symptom), photophobia, nausea, fever, and delirium. The diagnosis is made after a lumbar puncture, and analysis of the culture and antibodies .Syphilis
A century ago, patients with general paresis due to cerebral syphi-

litic infections constituted a high proportion of mental hospital admissions, and accounted for an appreciable part of the chronic population of such institutions. With the identiﬁ  cation in the early 
twentieth century of the causative agent, Treponema pallidum ,
and the development of effective methods of treating syphilis, this condition has become relatively rare. Historically, the study of syphilis of the central nervous system has been of great interest to psychiatrists due to the light it sheds on the nature of the relation-ship between cerebral and mental disease. It was one of the ﬁ  rst 
mental disorders for which a speciﬁ  c organic aetiology was demon-
strated, and the ﬁ  rst to respond to a medical treatment.
Syphilis remains a major problem in certain areas of the world.

Syphilis remains a major problem in certain areas of the world. 
Because during its early stages it is a genital ulcerative disease, syphilis facilitates the transmission of HIV and may be particularly important in contributing to HIV transmission in those regions where the rates of both infections are high.
Syphilis is a complex STD with an extremely variable clinical course. Neurosyphilis presents 5 years or more after the initial infection. It affects 10 per cent of non-treated cases, and can take several clinical forms.
(15)
◆ Asymptomatic neurosyphilis . Infected subjects have abnormal-
ities in the cerebrospinal ﬂ  uid (pleocytosis, elevated protein, and 
reactive VDRL score), but no symptoms or signs of central ner-vous system disorder. It can evolve into a symptomatic form or remit on its own.

◆ Meningovascular syphilis.  Appears within 1 to 5 years of pri-
mary infection, although it can occur as early as 6 months and as late as 12 years.
(16) In the clinical picture, the patient may develop 
stroke syndromes of subacute onset with a preceding encephalic picture, including psychiatric disturbances such as lability or personality changes. The patient may complain of headache, lethargy, and malaise, and may experience difﬁ  culty in concen-
tration and exhibit faulty judgement. Emotional instability and irritability are common. Mental deterioration may progress to dementia, which can be accompanied by delusional symptom-atology and episodes of excitation.
(16)
◆ General paresis.  This form of parenchymal neurosyphilis is also 
known as  dementia paralytica or general paralysis of the insane.

(16)
known as  dementia paralytica or general paralysis of the insane. 
It usually ﬁ  rst appears some 20 years after the initial infection. 
Its initial symptoms are memory disturbance, dysarthria, and hyper-reﬂ  exia, which may be accompanied by personality changes 
and irritability—in many cases the latter are the presenting abnormalities. The symptoms progress to dementia with abnor-mal motor function and psychotic symptoms. These organic psychoses were frequent in the pre-penicillin era and are known for their ﬂ  orid clinical picture—prominent euphoric mood, 
expansive demeanour, and delusions of power, wealth, or social position. Other cases may resemble depressive psychosis with somatic delusions .
◆ T abes dorsalis.  This condition is a degeneration of the ascending 
ﬁ bres from the dorsal root ganglia, resulting in atrophy of the

ﬁ bres from the dorsal root ganglia, resulting in atrophy of the 
dorsal roots and demyelinization in the posterior columns of the Table 5.3.5.2  Aetiology of delirium in HIV-infected patients
Infections Encephalitis due to HIV, syphilis, toxoplasmosis, 
cryptococcosis, coccidioidomycosis, progressive 
multifocal leucoencephalopathy, herpesvirus
Abstinence Alcohol, opiatesMetabolic Depletion of volume, hydro-electrolytic alterations, 
transfusions
Hypoxia Pneumonia with respiratory, compromiseDeﬁ  ciencies B-complex vitaminsCerebral vascular event
Medication Anticholinergics, central nervous system depressors
Intracranial mass Haematoma, neoplasiasToxic Drugs of abuse5.3.5 psychiatric aspects of infections

SECTION 5  psychiatry and medicine 1094
cord. It can develop from 3 to 20 years after the initial infection. 
Main symptoms are the loss of position reﬂ  exes, ataxia, vibration 
sense, incontinence, and lacinating pains involving many areas of the body .
Diagnosis and management
The clinical picture of neurosyphilis is so variable that routine 
serological testing upon admission to psychiatric inpatient units has been recommended. In clinical practice, a rise in atypical syn-dromes with minor symptomatology has been attributed to partial suppression of the infection during its early stages by antibiotics taken for other reasons.
(16) The diagnosis of neurosyphilis should 
be considered on the basis of the patient’s symptoms and clinical signs, and conﬁ  rmed by serology and analysis of the cerebrospinal 
ﬂ uid.
Penicillin is the drug of choice for T. pallidum  infections, and in

ﬂ uid.
Penicillin is the drug of choice for T. pallidum  infections, and in 
the treatment of neurosyphilis, but the dosage must achieve trepo-nemicidal levels within the cerebrospinal ﬂ  uid. In untreated cases, 
death usually occurs within 4 to 5 years. If treatment is given early, the condition usually remits; in already established cases, the pro-gression of the disease can be halted. Antipsychotics are indicated for the symptomatic management of the excitement and psychotic symptoms that these patients may present. Clinicians should have in mind that all patients who have syphilis should be tested for HIV .
Other sexually transmitted diseases

A diverse range of psychological symptomatology is associated with STDs, in which maladaptive or pathological responses to infection (or fear of infection) may occur. Most of the studies that evaluated the psychological effects of having a STD have been carried out in patients attending genitourinary clinics, and focused on genital herpes, a common, recurrent, and painful infection. The response to diagnosis of a STD can include depression, anxiety, anger, social withdrawal, feelings of loneliness, and sexual dysfunc-tion.
(17,18) Also, high rates of hypochondriasis and veneroneurosis

(17,18) Also, high rates of hypochondriasis and veneroneurosis 
(a strong but unfounded conviction of having a venereal disease) are found in STD clinics and are frequently associated with psychi-atric morbidity. Psychological interventions can effectively reduce the distress associated with STDs, contribute to the control of the infection, increase compliance with medication regimens, and reduce somatic symptoms misattributed to a STD.
Tuberculosis
In spite of pharmacological advances, tuberculosis continues to be a serious public health problem in many parts of the world, espe-cially due to the increased tuberculosis rate in HIV-infected patients and the appearance of multidrug-resistant tuberculosis.
Tuberculosis patients may present with vegetative signs suggestive 
of depression, especially the elderly and those in the symptomatic 
stages of HIV infection. The initial depressive symptoms are weight

stages of HIV infection. The initial depressive symptoms are weight 
loss, lethargy, lack of interest, and mental confusion. They may also develop sleep disturbances due to night sweats and nocturnal coughing.
Tuberculosis patients quite frequently present with neuropsychi-
atric symptoms, which can be related to very different circumstances. First, clinicians should bear in mind that tuberculosis infection

atric symptoms, which can be related to very different circumstances. First, clinicians should bear in mind that tuberculosis infection 
often develops in patients who previously had a severe psychiatric pathology, such as alcoholism or intravenous drug abuse, or in the chronic mentally ill. Also, the most common psychiatric symp-toms, such as emotional lability and depression, could be related, among other factors, to the feeling of invalidity that accompanies the illness, and its social stigma. In addition, the preventive treat-ment of those in contact with the patient can trigger feelings of guilt. In some cases, tuberculosis leads to chronic respiratory dis-ease, which is also associated with depressive symptoms, suicidal ideation, and cognitive impairment, particularly in debilitated patients.
Neuropsychiatric disorders in patients with tuberculosis can also

Neuropsychiatric disorders in patients with tuberculosis can also 
be related to cerebral infections: tuberculous meningitis, poten-tially a very serious complication, develops in 5 per cent of all cases. Since these patients frequently present with mental symptoms that can ﬁ  gure prominently from the outset and even precede overt 
signs of meningeal infection, the correct diagnosis should be established urgently, in order to institute speciﬁ  c therapy as soon as 
possible.
Sputum tests, cultures, and chest radiographs, as well as a tubercu-lin skin test, are standard diagnostic tools. In cases of suspected tuberculous meningitis, a spinal puncture is necessary to determine whether the patient has lymphocytosis and a moderate increase in protein. The diagnosis is conﬁ  rmed when tubercle bacilli can be 
identiﬁ  ed or cultured from the ﬂ  uid; however, since irreversible 
brain damage may result from waiting for cultural conﬁ  rmation, it

brain damage may result from waiting for cultural conﬁ  rmation, it 
is often necessary to begin therapy on the basis of a presumptive clinical diagnosis. The brain scan may show hydrocephalus, focal infarcts, and exudate in basal brain cisterns.
(19)
It is important in psychiatric settings that suspected tuberculosis 
patients receive a proper diagnostic evaluation, not only for the sake of their own health but also for that of other patients who may be exposed to the infection in the unit. It may be necessary to trans-fer psychiatric inpatients with tuberculosis to a ward where isola-tion can be assured. The Centres for Disease Control recommend routine tuberculosis screening for patients in HIV risk groups, and for residents of mental health facilities.
(20)
The most commonly used drugs for the treatment of tuberculosis

(20)
The most commonly used drugs for the treatment of tuberculosis 
are isoniazid, rifampicin, pyrazinamide, ethambutol, and strepto-mycin. Compliance is vital to achieve effective treatment.
Lyme disease
First described in the United States in 1975, this infection has also been reported in Europe, Australia, and other parts of the world. It is caused by the spirochaete Borrelia burgdorferi , which is carried 
and transmitted by the deer tick. The somatic symptomatology features a characteristic skin lesion, an expanding erythematous annular lesion which usually ﬁ  rst appears 3 to 32 days after the 
initial transmission and may last for several weeks. In 15 per cent of the patients, the disease progresses to a secondary phase marked by neurological symptoms, for example meningoencephalitis, radiculitis, central and peripheral neuropathy, and myelitis.
The neuropsychiatric symptomatology consists in difﬁ  culties

The neuropsychiatric symptomatology consists in difﬁ  culties 
involving memory, orientation, and calculation. Even years after the ﬁ  rst infection, patients can present with violent and impulsive

1095
behaviour, labile affect, and depression. Cases of psychotic or 
catatonic syndromes and chronic dementia have been described. Many patients with Lyme disease, who suffer from neurological symptoms, present with signs of encephalopathy with alterations in their sleep, affect, and memory. The diagnosis can be established from a serological analysis.
Encephalitis
Encephalitis may be caused primarily by a viral disease affecting the brain or can be a complication of bacterial meningitis, septicae-mia, or brain abscesses. It can occur after inﬂ  uenza, herpes simplex, 
measles, rubella infections, and also after vaccination. In the acute stage, the patient may present with headache, vomiting, and seizures. Patients may develop a confusional syndrome. In rare cases, the encephalitis may present with predominantly psychiatric symptoms. That is the case of herpesvirus encephalitis, which due to its damage to temporal lobes can cause a serious amnestic syndrome.

In clinical practice, the psychiatrist is more likely to see the com-
plications that appear after the acute episode in the form of anxiety and depressive syndromes, personality change, and dementia. In the early years of life, encephalitis may be followed by behav-
ioural disorders.
(16)
Infectious mononucleosis
The Epstein–Barr virus causes 90 per cent of all cases of infectious 
mononucleosis. It can appear at any age, but the illness tends to manifest itself clinically in adolescents and young adults.
The most important symptoms are fever, general malaise, diffuse 
lymphadenopathies, and laryngitis. However, complications can lead to encephalitis and paralysis of the cranial nerves. In the case of encephalitic compromise, delirium can result. Depressive syn-dromes have also been observed after an acute infectious episode, accompanied by fatigue.
Brucellosis

This infection is produced by micro-organisms of the genus Brucella , and is transmitted by exposure to or ingestion of contam-
inated animal products, especially unpasteurized milk products, or contact with infected animal tissues. Onset can be insidious, since it mimics other more common illnesses, with low fever, fatigue, and sweating, but 10 to 20 per cent of cases present with spleno-megaly. The psychiatric manifestations of the disease can include depressive or anxious syndromes. Diagnosis can be conﬁ  rmed by 
blood or lymph cultures or bone marrow biopsy, although the majority of diagnoses are made serologically.
Fernandez, F. and Ruiz, P . (eds.) (2006). Psychiatric aspects of HIV/AIDS .
Lippincott Williams & Wilkins, Philadelphia, PA.
APA AIDS resource center: www.psych.org/AIDS
CDC resource center: www.cdc.gov/stdReferences
 1. Forstein, M. (1988). Understanding the psychological impact of AIDS:

 1. Forstein, M. (1988). Understanding the psychological impact of AIDS: 
the other epidemic. New England Journal of Public Policy ,4, 159–73.
 2. Catalan, J., Burgess, A., and Klimes, I. (1995). Psychological medicine of 
HIV infection . Oxford Medical Publications, Oxford.
 3. Ciesla, J.A. and Roberts, J.E. (2001). Meta-analysis of the relationship 
between HIV infection and risk for depressive disorders. The American 
Journal of Psychiatry ,158, 725–30.
 4. Markowitz, J.C., Rabkin, J.G., and Perry, S.W. (1994). Treating 
depression in HIV-positive patients. AIDS ,8, 403–12.
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for depression in patients with HIV and AIDS: a randomized, placebo-
controlled trial. The American Journal of Psychiatry ,156, 101–7.
 6. Markowitz, J., Kocsis, J.H., Fishman, B., et al. (1998). Treatment of

 6. Markowitz, J., Kocsis, J.H., Fishman, B., et al. (1998). Treatment of 
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 7. Blanch, J., Rousaud, A., Hautzinger, M., et al. (2002). Assessment of the 
efﬁ cacy of a cognitive-behavioral group psychotherapy programme 
for HIV infected patients referred to a consultation-liaison psychiatry department. Psychotherapy and Psychosomatics ,71, 77–84.
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in psychiatric inpatients: an unlinked anonymous study. British Journal 
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infection. Drugs ,4, 599–610.
10. Singh, A.N., Golledge, H., and Catalan, J. (1997). Treatment of HIV 
related psychotic disorders with risperidone: a series of 21 cases.

related psychotic disorders with risperidone: a series of 21 cases. 
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11. Kierburz, K., Zettelmaier, A., Ketonen, L., et al. (1991). Manic 
syndrome in AIDS. The American Journal of Psychiatry ,148, 1068–70.
12. Mijch, A.M., Judd, F.K., Lyketsos, C.G., et al. (1999). Secondary mania 
in patients with HIV infection: are antiretrovirals protective? Journal of 
Neuropsychiatry and Clinical Neurosciences ,11, 475–80.
13. Breitbart, W., Marotta, R., Platt, M.M., et al. (1996). A double-blind 
trial of haloperidol, chlorpromazine and lorazepam in the treatment of delirium in hospitalised AIDS patients. The American Journal of 
Psychiatry ,153, 231–7.
14. Fernandez, F., Levy, J.K., and Mansell, P .W. (1989). Management 
of delirium in terminally ill AIDS patients. International Journal 
Psychiatry in Medicine
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15. Simon, R.P . (1985). Neurosyphilis. Archives of Neurology ,42, 606–13.
16. Lishman, W.A. (1998). Organic psychiatry  (3rd edn). Blackwell Science, 
Oxford.
17. Catalan, J., Bradley, M., Gallwey, J., et al. (1981). Sexual dysfunction 
and psychiatric morbidity in patients attending a clinic for sexually transmitted diseases. British Journal of Psychiatry ,138, 292–6.
18. Hedge, B. (1997). Sexually transmitted diseases. In Cambridge 
handbook of psychology, health and medicine  (eds. A. Baum, S. Newman, 
J. Weinman, R. West, and C. McManus), pp. 584–5. Cambridge University Press, Cambridge.
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20. Dooley, S.W., Castro, K.G., Hutton, M.D., et al. (1990). Guidelines for

20. Dooley, S.W., Castro, K.G., Hutton, M.D., et al. (1990). Guidelines for 
preventing the transmission of tuberculosis in health-care settings, with special focus on HIV-related issues. Morbidity and Mortality 
Weekly Report ,39 (RR-17), 1–29.5.3.5 psychiatric aspects of infections

SECTION 5  psychiatry and medicine 1096
5.3.6 Psychiatric aspects of surgery 
(including transplantation)
Attention to psychiatric disturbances and to emotional distress 
is important in the surgical setting, from the time of the initial diagnostic assessment, to the perioperative period and the phase of subsequent recovery and rehabilitation. Psychiatric illness and psychological factors, which are not taken into account prior to surgery, may contribute to inaccurate diagnoses, unrealistic assess-ment of the surgical risk, unnecessary surgery, and complications that could have been avoided or minimized. This chapter will address these factors and provide an approach to the consideration of psychiatric factors and interventions in this setting.
Preoperative assessment and intervention

The assessment of all patients being considered for surgery should include a brief evaluation of their current emotional state, cogni-tive functioning, personal circumstances, present or past history of psychiatric illness, and personality and coping style, as these factors may affect their adjustment to surgery. Psychiatric consultation may be indicated for a number of speciﬁ  c reasons discussed below.
Psychological contributors to the patient’s 
physical symptoms
The most common psychological factor that complicates the sur-
gical assessment is a low pain threshold and a tendency to soma-tize, i.e. to experience and communicate emotional distress in physical terms. When emotional factors amplify somatic symp-toms, it is more difﬁ  cult to distinguish organic from functional dis-

orders on the basis of the clinical history. At the extreme end of the continuum of somatization is the dramatic presentation of physi-cal symptoms, which may mimic a surgical condition, in the absence of organic disease. This syndrome may fulﬁ  l criteria for a 
somatoform disorder, such as a somatization disorder, conversion disorder, or somatoform pain disorder.
(1) In such cases, careful 
attention to the objective indications for surgery is required. Individuals with a body dysmorphic disorder, a syndrome of per-ceived or imagined ugliness, may present with repeated requests for cosmetic surgery.
(2) However, cosmetic surgery is unlikely to

(2) However, cosmetic surgery is unlikely to 
relieve the body dissatisfaction of such patients, whose condition has much in common with obsessive–compulsive disorder. Dissatisfaction with the results of surgery is common in patients with body dysmorphic disorder, and litigiousness and threats towards the treating surgeon may occur in a small proportion of cases. In general, the failure of clinicians to consider the contribu-tion of somatization to the clinical presentation may lead to unnecessary or inappropriate surgery. When this occurs, postsur-gical complications may interfere with the subsequent evaluation of persistent physical symptoms. Somatoform disorders are dis-cussed further in Chapter 5.2.2.
Although physicians commonly consider that emotional factors 
may amplify physical symptoms, the possibility that disease has 
been intentionally simulated or fabricated is usually not entertained. Factitious disorder refers to a syndrome in which such behaviour is

been intentionally simulated or fabricated is usually not entertained. Factitious disorder refers to a syndrome in which such behaviour is 
enacted for no apparent reason, other than to assume the patient role. This is in contrast with malingering, in which there may be reports of physical symptoms motivated by the desire for some speciﬁ  c secondary gain, which may be ﬁ  nancial or compensation-
related. While relatively rare, factitious disorder poses particular challenges, in both detection and treatment, to psychiatric and sur-gical teams. Individuals with this disorder may produce or simulate disease in various ways, such as by self-inﬂ  icting wounds that

require surgical intervention or by surreptitiously contaminating themselves to produce infection. Patients with this condition may also communicate plausible symptoms of a surgical condition. Such patients are at risk to receive unnecessary surgery and should be regarded as suffering from a serious and potentially life-threat-ening condition. The majority of such patients are unwilling to accept psychological or psychiatric assistance, but an ongoing, sup-portive relationship with a medical caregiver may diminish this symptom pattern. Factitious disorder is discussed further in Chapter 5.2.9.
Capacity to consent to surgery
Providing information and obtaining informed consent are routine and essential aspects of preoperative care provided by the surgical team. Informed consent to a surgical procedure requires disclosure of pertinent information by the treating physician, and under-standing of the information, decisional capacity, and voluntary choice on the part of the patient.

(3) The decisional capacity of 
patients depends on their ability not only to understand informa-tion relevant to the decision, but also to apply it to their own situa-tion and to express a consistent voluntary choice.
(4) Information 
required by patients to make an informed surgical decision includes the rationale, risks, and beneﬁ  ts of the surgery, the potential 
alternative treatments, and the risk of not proceeding with surgery. In most jurisdictions, the emergency treatment of incapable persons is permitted, when substitute consent is not available, unless the clinician has reason to believe that the person would refuse such treatment if he or she were capable.
(3) When it is not 
an emergency, substitute consent must be obtained on behalf of individuals who are incapable of providing informed consent. The legal requirements for substitute consent vary in different jurisdictions.
The capacity to provide informed consent may be impaired by

The capacity to provide informed consent may be impaired by 
cognitive dysfunction, by psychiatric illness, or by contextual factors, such as the clarity and relevance of the information disclosed or the manner of disclosure. If screening by the treating surgeon indicates that the patient may be incapable, a psychiatric consultation may be requested to evaluate the patient’s decisional capacity.
(5) Patients 
with cognitive impairment or a major psychiatric disorder, such as schizophrenia, are not necessarily incapable of making treatment decisions, unless these conditions affect their understanding and appreciation of information relevant to the decision. Numerous tools have been developed to assess decisional capacity but there is no current gold standard.
(6)
Obtaining informed consent for surgery is not only a legal and 
ethical requirement, but also a crucial dimension of the surgeon–patient relationship. In some cases, treatment refusal reﬂ  ects a

ethical requirement, but also a crucial dimension of the surgeon–patient relationship. In some cases, treatment refusal reﬂ  ects a 
breakdown in the relationship between the surgeon and the patient more than it does an informed decision of the patient to reject a

1097
recommendation for surgery. When this occurs, attention to the 
physician–patient relationship, and the provision of additional information, may help to relieve the impasse so that an informed decision can be made. In other cases, treatment of a major psychi-atric illness, such as a psychotic episode in a patient with schizo-phrenia, is necessary to restore the patient’s capacity to provide consent.
Assessment of the response to surgery
Surgical patients face numerous stressors, including the fear of pain, disﬁ  gurement, and the loss of control, as well as the possibility 
of major medical complications and death. The response to these stressors may be affected by the nature of the illness and the surgical procedure, its personal meaning, the prior history of trauma, the support which is anticipated and perceived from medical caregiv-ers and signiﬁ  cant others, and the prior experience of the individual

with medical or surgical procedures. The age and life stage of the individual, the risk associated with the procedure, and the prognosis of the underlying or associated medical conditions may also affect the psychological response in the perioperative period. Apprehension and mistrust are more common in those who have previously suffered from the adverse effects of missed or delayed diagnosis or treatment. Attitudinal factors, including positive expectations and the desire to participate actively in the recovery process, may also affect clinical outcomes. The desire to maintain a sense of control may be adaptive during the preparation and rehabilitation phases but may be associated with greater distress immediately following surgery, when there is an inescapable and predominant requirement to depend on others.
(7) Those with more 
attachment anxiety, i.e. concern about the availability of support from others, may beneﬁ  t from predictability and reliability in rela-

tion to caregivers, whereas those who tend to be more self-sufﬁ  cient 
may beneﬁ  t most from strategies which promote self-reliance and 
self-care.
(8, 9)
There has been particular interest in psychosocial issues in the 
setting of transplantation surgery. This occurred, in part, because of the desire of transplant programmes to select optimal candidates for organ transplants, which were experimental and/or in scarce supply. However, the psychiatric and psychosocial selection criteria for transplant surgery have become less stringent, as the transplan-tation of particular organs has become more routine.
(10) At present, 
psychosocial evaluation of transplant candidates by a multi-disciplinary team allows for the identiﬁ  cation, treatment, and

psychosocial evaluation of transplant candidates by a multi-disciplinary team allows for the identiﬁ  cation, treatment, and 
monitoring of factors that may affect compliance, morbidity, and psychosocial outcomes. Organ transplants from living donors, such as for bone marrow, kidney, and liver transplantation, are unlike most other surgical interventions in that they necessitate surgery for individuals without pre-existing disease. Psychosocial evalua-tion of such donors includes consideration of the process of decision-making and informed consent, the adaptive capacities of the individual, the degree of social support, and the relationship of the donor to the recipient.
(11) Although there has been concern about 
the psychological consequences of such surgery, the available evidence suggests that organ donation is usually well tolerated and experienced in positive terms by the donor, particularly when the surgical and medical outcomes are favourable.
(12)

(12)
There is now increasing evidence that the systematic preoperative 
education of patients and their family caregivers in a therapeutic context may enhance adjustment to surgical procedures.(13)
Postoperative education may also improve subsequent rehabilita-
tion following surgical procedures. Such approaches are consistent with modern Western trends towards consumerism and patient empowerment, in which greater emphasis is placed on assisting patients to assume more responsibility for their medical course and treatment outcome. This approach has also been necessitated by the trend towards earlier hospital discharge of surgical patients into the community where much more self-care is required.
Anxiety

Anxiety
Preoperative anxiety is common and may be particularly problem-atic in patients awaiting procedures such as transplantation, which usually occur in the course of a life-threatening condition, and are associated with long and unpredictable waiting periods for surgery. Anxiety has been reported to be more common in younger patients, in females, and in those who are unmarried or who have less perceived social support.
(14) Research suggests that preoperative 
anxiety may complicate postoperative recovery through behav-ioural and physiological mechanisms.
(15) Symptoms of anxiety can 
usually be managed with education and reassurance, but when they are persistent and problematic, interventions such as progressive relaxation and guided imagery may be helpful both to reduce symptoms of anxiety and to enhance feelings of self-control.
(16)
Some patients beneﬁ  t from a benzodiazepine to reduce preopera-

(16)
tive anxiety, but those with antecedent anxiety disorders may require more intensive intervention, as outlined in Chapter 4.6.1. Prior to elective procedures, patients with speciﬁ  c blood or needle 
phobias may beneﬁ  t from systematic desensitization. Those with 
comorbid panic disorder may require a higher dose of anxiolytic medication in the preoperative period. The surgical team should be aware of such treatment so that the medication can be restarted promptly after surgery, to avoid symptoms of withdrawal and anxi-ety. If oral medications cannot be reinstituted for a prolonged peri-od of time after surgery, intramuscular lorazepam or intravenous lorazepam or diazepam may be used.
It is important to detect and treat mood disorders prior to surgery because they are associated with increased surgical morbidity and mortality, and with reduced treatment compliance in the postop-erative period.

(17) Anaesthetists must be aware of any drugs taken 
to treat and prevent bipolar and depressive disorders, because some can signiﬁ  cantly prolong muscle paralysis secondary to neu-
romuscular blockade. Furthermore, attention should be paid to serum lithium levels and signs of lithium toxicity since they may be affected by the patient’s ﬂ  uid and volume status. Conventional 
heterocyclic antidepressants and selective serotonin reuptake 
inhibitors can be continued until the time of surgery, and then restarted postoperatively, when oral medications can be tolerated. Selective serotonin reuptake inhibitors are known to affect platelet serotonin levels and platelet aggregation and to be occasionally associated with prolonged bleeding times, increased perioperative blood loss, and an increased subsequent need for transfusion.
(18)

(18)
Patients receiving monoamine oxidase inhibitors (MAOIs) are usually advised to discontinue this medication for 1 to 2 weeks prior to their surgery, although this recommendation must be weighed against the risk of withdrawal symptoms and of  precipitating 5.3.6 psychiatric aspects of surgery (including transplantation)

SECTION 5  psychiatry and medicine 1098
a current depression. The medical charts of patients receiving 
MAOIs should be clearly labelled to advise that all drugs admin-istered should be screened for their interactions with these drugs and that pethidine (meperidine) and dextromethorphan in par-ticular should not be prescribed due to risk of a serotonin syn-drome, which is associated with gastrointestinal, neurological, cardiovascular, and psychiatric symptoms. In addition, hospital charts of patients taking MAOIs should be clearly marked to indicate that they must avoid foods containing tyramine. Patients with bipolar disorder should be monitored for mood alterations since they may be at risk of developing hypomania or mania when steroid medications are used following transplantation surgery.

These disorders, most commonly related to schizophrenia or bipo-lar disorder, pose challenges which vary depending upon the requirements of the surgery and the patient’s mental status. Patients with schizophrenia may be at increased perioperative risk for hypo-tension, hypothermia, confusion, infection, and for ileus, in those who undergo abdominal surgery. These complications may occur due both to pathology of the endocrine, immune, and cardiovascu-lar systems associated with schizophrenia and to the effects of antipsychotic medications.
(19) Those who are being treated with a

(19) Those who are being treated with a 
low-potency antipsychotic may be switched to a high-potency agent to decrease the risk of hypotension, particularly with cardio-vascular surgery in the postoperative period. For their own com-fort and for that of others, individuals who are actively psychotic may require special arrangements, such as a single room, close or constant observation, and, when feasible, greater family involve-ment. Such patients require closer monitoring for many reasons, including the increased likelihood that they may misinterpret com-mon ward events as threatening and because they may be at increased risk for exacerbation of their underlying condition and for the occurrence of delirium.
Cognitive disorders

The capacity of patients to understand information and to provide a coherent account of their symptoms is fundamental to the process of diagnosis, informed consent, and assessment of the indications for surgery and the risk of speciﬁ  c postoperative complications. 
Cognitive impairment prior to surgery may complicate these pro-cesses and may be associated with an increased risk of delirium or dementia in the postoperative period. In such cases, neuropsycho-logical testing may be indicated prior to elective surgery to estab-lish a baseline, to assist in the evaluation of decisional capacity, and, to aid in the prediction of postoperative delirium or worsen-ing of dementia.
Patients with personality disorders are more likely to have greater difﬁ culty than others adapting to the multiple and unpredictable 
stresses associated with surgery. Those with impulsivity may have difﬁ culty adhering to the preoperative and postoperative regimen

stresses associated with surgery. Those with impulsivity may have difﬁ culty adhering to the preoperative and postoperative regimen 
and those who are suspicious and mistrustful may be more limited in their ability to form effective treatment relationships and to make treatment decisions, in which an enormous degree of trust is required. Those with a borderline personality disorder may be highly sensitive to feelings of personal injury or neglect and may 
tend to idealize some caregivers and to denigrate others. These responses may create problematic divisions amongst the treatment team and may adversely affect the care of the patient. A psychiatric consultant may be of help to provide patient support and to educate staff about the underlying psychiatric disorder in such individuals, who may otherwise be viewed negatively by staff who regard their behaviour as simply wilful or manipulative.
Substance abuse disorders

The preoperative assessment should include enquiry about sub-stance use, in order to adjust current medication appropriately and to prevent the occurrence of postoperative withdrawal syndromes. Consultation psychiatrists may play a role in continuing medical education about the value of routine, non-judgemental screening for substance use in medical patients, and about the importance of recording these details in the medical record.
Assessment of psychotropic medications
The pharmacological effects of psychotropic medications must be taken into account in the perioperative period. Important factors  that affect the risks and beneﬁ  ts associated with psychotropic med-
ication use perioperatively include:
1 End-organ sensitivity to side effects based on medical comorbid-
ity and organ dysfunction;
2 direct effects of psychotropic medications and their potential 
interactions with anaesthetic and analgesic agents likely to be prescribed;

3 route of access available (oral, suppository, subcutaneous, 
intramuscular, intravenous);
4 risk of withdrawal symptoms and recurrence or relapse of a
psychiatric disorder if psychotropic medications are to be 
discontinued.
(20)
Information on drug–drug interactions is constantly being 
updated and current information can be obtained from internet sites such as http://www.drugdigest.org/DD/Home or http://search.medscape.com/drug-reference-search.
Postoperative complications and 
Agitation and delirium
Agitation is a common postoperative problem, the frequency of

Agitation is a common postoperative problem, the frequency of 
which depends upon the characteristics of the disease, the nature of the surgery and its complications, and the pre-existing vulnera-bility of the patient. A concerted effort should be made to identify the source of the agitation, which may be a worsening of the medi-cal condition, inadequately controlled pain, or delirium. Delirium, which is described in more detail in Chapter 4.1.1, is a common complication, which develops in more than one-third of cases fol-lowing surgery.
(21) Higher rates of delirium are found following 
longer procedures, due to intraoperative hypoxemia, following car-diac surgeries, due to hypoperfusion and microemboli formation, following orthopaedic procedures, due to fat emboli, and following cataract surgery, due to the impact of vision loss and of ophthalmic drugs with anticholinergic side effects.
(22)

1099
Measures to prevent and ameliorate delirium include the identi-
ﬁ cation and treatment of predisposing risk factors and reversible 
causes, symptomatic treatment, and environmental interventions to reduce distress and agitation. The latter may include measures to prevent sensory deprivation and disorientation, to monitor safety, and to educate patients and family members about the con-dition. When distress or agitation associated with delirium threaten the safety and care of the patient, pharmacologic interventions may be necessary. There have been trials of cholinesterase inhibitors
(23)
and of atypical antipsychotics in those patients who can take oral medications, but haloperidol remains the ﬁ  rst-choice medication

(23)
and of atypical antipsychotics in those patients who can take oral medications, but haloperidol remains the ﬁ  rst-choice medication 
for management of delirium-associated agitation. It is preferred because it has fewer active metabolites and fewer anticholinergic and sedative effects than other antipsychotic medication and because it can be administered intravenously. This route of admin-istration is usually safe, although arrhythmias with its intravenous use have been reported in patients with histories of alcohol abuse or with cardiomyopathy.
(24) Benzodiazepines should be used to 
treat withdrawal from alcohol and sedative-hypnotics using stan-dard protocols.
Delirium may be highly distressing for both patients and family 
caregivers.
(25) Some patients subsequently retain disturbing mem-

ories of their experience during a delirium. Such traumatic recall may also occur, in rare instances, when there has been inadequate anaesthesia. In these cases, patients and their family caregivers typ-ically appreciate a discussion of their concerns and the opportunity to review these events with the surgeon and the anaesthetist. A small number of patients with these disturbing experiences develop symptoms of post-traumatic stress disorder and may beneﬁ  t from a brief course of psychotherapy or pharmacotherapy 
to alleviate their symptoms.
Ventilator weaning
Some patients experience difﬁ  culty being weaned from the venti-

lator due to anxiety, depression, delirium, or other psychological factors related to their disease or to the ICU environment. Behavioural approaches to facilitate weaning may include relax-ation techniques that do not depend on observation or manipula-tion of breathing, guided imagery, and/or biofeedback.
(26) Weaning 
problems due to anxiety typically respond to benzodiazepines or to haloperidol, administered in a single dose prior to weaning. Apathetic or depressed patients who have difﬁ  culty being weaned 
may beneﬁ  t from a psychostimulant.
(27) When delirium is the 
cause of weaning problems, its underlying cause should be identi-ﬁ ed and treated.
Pain management
Effective pain management is a fundamental aspect of postopera-
tive treatment and may reduce distress, agitation, sleep disturbance,

tive treatment and may reduce distress, agitation, sleep disturbance, 
anxiety, mood symptoms, and behavioural disorders. Suboptimal pain management may occur due to inadequate assessment of this 
symptom, insufﬁ  cient knowledge of the pharmacokinetic and 
pharmacodynamic properties of analgesic medication, and unfounded concerns about ‘addiction’ . Further, some patients refuse to accept adequate analgesia because of misconceptions or personal beliefs regarding the importance of stoicism, vigilance, or personal control. Consultant psychiatrists may help patients to address their concerns about analgesic medication and analgesic adjuvants and may act also as advocates or intermediaries for 
patients to ensure adequate analgesia.
Sleep disturbances, including reduced total sleep time, fragmenta-

tion of sleep, frequent arousals and awakenings, and reduced slow-wave sleep, are common in the immediate postoperative period. These disturbances may be caused by multiple factors, including the noise, temperature and light of the hospital environment, neu-roimmunological and other changes associated with the surgical insult, and anaesthetic and analgesic medications.
(28) Daytime 
sleeping, related to prolonged bed rest, lack of intellectual and social stimulation, and reduced circadian cues, may disrupt nor-mal sleep chronobiology and increase difﬁ  culty with night-time 
sleep.
Treatment of sleep disturbances should be directed to the identi-
ﬁ ed cause. In those patients in whom anxiety or the intrusiveness

sleep.
ﬁ ed cause. In those patients in whom anxiety or the intrusiveness 
of the hospital environment is the main cause of the sleep distur-bance, benzodiazepines may be temporarily used. When there are concerns about substance abuse, newer non-benzodiazepine hyp-notics may be preferable, due to the lower risk of tolerance associ-ated with their use.
(28) Caution should be exercised with patients 
for whom benzodiazepine-induced nocturnal respiratory compro-mise may be problematic or with elderly patients who are suscep-tible to cognitive compromise or to falls.
Cognitive impairment is a common short-term and long-term complication of major surgery, particularly in those with more advanced age. Gradual recovery of cognitive functions occurs in most patients within 3 months after surgery, although it may take as long as 6 to 12 months.
(29) Delirium that is slow to resolve may

(29) Delirium that is slow to resolve may 
be an early sign of an associated dementing illness or of a cerebral insult that has occurred during or after surgery. Cognitive impair-ment may be permanent when there has been irreversible brain damage due to neurosurgery or perioperative complications, such as hypoxia or stroke. Neuropsychological testing may be helpful to document or track changes in cognitive functioning. Education of primary caregivers about the risk and manifestations of cognitive impairment is essential, and institution of home supports and respite care for patients and families facing this complication may be necessary. Some patients with cognitive impairment may also beneﬁ  t from neurorehabilitation interventions.
Adjustment issues
Longer-term problems in adjustment may occur, particularly fol-
lowing disﬁ  guring surgeries, such as facial surgery, amputations,

lowing disﬁ  guring surgeries, such as facial surgery, amputations, 
ostomies, or following procedures such as organ transplantation, which impose complicated postoperative regimens. Sexual difﬁ  -
culties that result from procedures that compromise the neural input or functional integrity of genital structures, or that nega-tively affect body image or feelings of attractiveness, may be dis-turbing to patients and spouses who may beneﬁ  t from speciﬁ  c 
enquiry and assistance. Patients and their families should be informed about the possibility of adjustment problems with such surgeries and should be given information about available resourc-es. A minority of patients develop clinically signiﬁ  cant mood or 
anxiety disorders or signiﬁ  cant compliance problems during the 5.3.6 psychiatric aspects of surgery (including transplantation)

SECTION 5  psychiatry and medicine 1100
rehabilitation phase which may necessitate psychiatric consulta-
tion and intervention.
Prolonged dysfunction
Prolonged and disproportionate pain and disability occur in a subset of patients. In some of these cases, the surgery was under-taken to relieve refractory symptoms that subsequently proved to be functional or medically unexplained. This may occur with hys-terectomies performed to relieve pelvic pain and in surgery to relieve chronic back pain. In other cases, persistent disproportion-ate symptoms may be perpetuated by secondary gain of a ﬁ  nancial 
or social nature, or by opiate dependence. Undiagnosed and untreated mood, anxiety, and somatoform disorders may also con-tribute to persistent symptoms. The consultation psychiatrist may be called upon to identify these factors and to help distinguish them from undetected medical/surgical pathology or from the effects of inadequate pain regimens.

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5.3.7 Psychiatric aspects of cancer
Psycho-oncology addresses the two major psychiatric and psycho-
logical dimensions of cancer: ﬁ  rst, the responses of patients and

logical dimensions of cancer: ﬁ  rst, the responses of patients and 
their families at all stages of disease and the psychological stresses on health professionals delivering their care. The patient and physi-cian relationship, dependent on effective communication, impacts

1101
the care of all patients, at every visit, at all sites and stages of cancer, 
and during all treatments. The second dimension addresses the psychological, behavioural, and social factors that inﬂ  uence cancer 
risk, detection, and survival.
Many cancer centres and hospitals now have multi-disciplinary 
psychosocial teams consisting of clinicians and clinical investiga-tors from psychology, psychiatry, social work, nursing, and clergy. These teams provide consultation for patients and their caregivers, psychosocial education for oncology staff, and collaboration in studies in which quality of life is important. In addition, active research in brain, immune, and endocrine links is occurring, par-ticularly in the mechanism of cytokines in producing ‘sickness behaviour’ that may provide a biological basis for common symptoms of fatigue, depression, anxiety, weakness, and cognitive chances in cancer patients.
(1, 2)
Despite the fact that many cancer centres and oncology divisions

(1, 2)
Despite the fact that many cancer centres and oncology divisions 
now have a psycho-oncology or psychosocial unit, only a few centres have programmes that include both research and training.
This chapter describes the common psychiatric disorders and 
psychosocial challenges experienced by cancer patients and the range of interventions available.
A key challenge for the oncologist is the differentiation of expected, tolerable, transient distress associated with cancer, such as fear, worry, and sadness, from excessive, disabling, persistent distress requiring therapeutic intervention. Most psychiatric disturbances in patients with cancer relate to their illness or treatment side effects.
(3) One-third of patients will experience distress that requires 
evaluation and treatment.(3–6) The percentage is greater among

evaluation and treatment.(3–6) The percentage is greater among 
younger patients, those with sites of cancer with poorer prognosis, for example, brain, pancreas, lung, and those who are hospitalized with greater level of illness causing confusional states and greater anxiety and depression.
(7,8)
Anxiety

(7,8)
Anxiety
Anxiety is the most common form of distress experienced by patients in the oncology setting (Table 5.3.7.1). It occurs with abnormal metabolic states: hypoxia, pulmonary embolus, sepsis, delirium, bleeding, cardiac arrhythmia, and hypoglycemia. Hormone-secreting neoplasms that produce psychiatric symptoms consistent with mood or anxiety disorder are pheochromocytoma, thyroid tumour, carcinoid, parathyroid adenoma, adrenocortico-tropic hormone-producing tumour, insulinoma, and paraneoplas-tic syndrome, an immunologic non-metastatic central nervous system complications of several tumours (particularly, lung and ovary) that may present with mood or cognitive changes.
Numerous medications produce symptoms of anxiety: corticoste-
roids, neuroleptics, bronchodilators, thyroxine, and psychostimulants. The antiemetics, including metoclopramide and prochlorperazine, 
which are widely used for chemotherapy-related nausea and vomit-

ing, produce restlessness, akathisias, and dystonias. Benzodiazepines promptly reduce the restless movements, anxiety, and agitation. Withdrawal states from alcohol, benzodiazepines, sedative-hypnotics, and opioids produce anxiety as prominent symptoms.
Some patients undergoing cyclic chemotherapy receiving highly 
emetogenic regimens develop anticipatory anxiety, nausea, and vomiting days to hours in advance of receiving the next cycle of treatment.
(9–11) More effective antiemetic regimens have signiﬁ  -
cantly reduced the frequency and severity of this problem. However, behavioural interventions paired with antianxiety medications continue to assist in providing relief from this distress.
Patients who have pre-existing phobias, panic attacks, 
generalized anxiety disorder, or obsessive–compulsive disorder are at risk of experiencing symptom exacerbations during treatment (Table 5.3.7.1).

(12) Phobias of needles, blood, hospitals, magnetic 
resonance imaging machines, or radiation simulators complicate a patient’s ability to tolerate hospital procedures or adhere to recom-mended treatments. Panic attacks superimposed on physical symp-toms of dyspnea and tachycardia may be partially alarming to patients.
(3,13) Patients with previous traumatic experiences may suffer 
a recurrence of intrusive re-experiences of painful memories, mal-
adaptive avoidant behaviour or withdrawal, and hypervigilance.(14,15)
Cancer patients with OCD may have increased difﬁ  culty during 
treatment. Intrusive fears may lead to indecisiveness regarding treatment options and reluctance to accept interventions with known therapeutic efﬁ  cacy. Excessively time-consuming rituals

treatment. Intrusive fears may lead to indecisiveness regarding treatment options and reluctance to accept interventions with known therapeutic efﬁ  cacy. Excessively time-consuming rituals 
may interfere with a patient’s adherence to medical appointments. Inﬂ exibility of thought, hostility, overwhelming distress, and occa-
sionally poor insight contribute to the challenge of engaging these patients and assisting them in accepting interventions.
Management . Anticipatory anxiety prior to medical interven-
tions responds to empathic validation of the fear, adequate prepa-ration to set realistic expectations for the encounter, and rehearsal of the dreaded event.
Signiﬁ  cant disabling anxiety symptoms are frequently treated

Signiﬁ  cant disabling anxiety symptoms are frequently treated 
pharmacologically with benzodiazepines, selective serotonin-reuptake inhibitors (SSRIs), mirtazapine, venlafaxine, buspirone, antihistamines, beta-blockers, or neuroleptics. Table 5.3.7.2 out-lines the benzodiazepines commonly used and their initial and Table 5.3.7.1  Causes of anxiety in patients with cancer
Situational
 Diagnosis of cancer, prognosis discussion
 Crisis, illness/treatment
 Conﬂ  icts with family or staff
 Anticipating a frightening procedure Awaiting results of tests
 Fears of recurrence after completing treatment
Disease-related
 Poorly controlled pain Abnormal metabolic states
 Hormone secreting tumors
 Paraneoplastic syndromes (remote CNS effects)
Treatment-related
 Frightening or painful procedures (MRI, scans, wound debridement)
 Anxiety-producing drugs (antiemetic neuroleptics, bronchodilators) Withdrawal states (opioids, benzodiazepines, alcohol)

Frightening or painful procedures (MRI, scans, wound debridement)
 Conditioned (anticipatory) anxiety, nausea, and vomiting with cyclic 
  chemotherapy
Exacerbation of preexisting anxiety disorder
 Phobias (needles, claustrophobia)
 Panic or generalized anxiety disorder Posttraumatic stress disorder (Holocaust survivors, Vietnam veterans, recall 
  of  the death of a relative with cancer)
 Obsessive compulsive disorder5.3.7 psychiatric aspects of cancer

SECTION 5  psychiatry and medicine 1102
therapeutic doses. A shorter half-life enhances control during the 
upward titration process and decreases the risk of accumulation and intoxications.
Depression in cancer patients requires early recognition and thera-peutic intervention. Depression is more challenging to diagnose in patients with cancer because illness produces many neurovegeta-tive symptoms: sleep disturbances, appetite reduction and weight loss, psychomotor retardation, fatigue, apathy, and poor concentra-tion.
(16) Focusing the assessment on the psychological symptoms of 
dysphoria, anhedonia, hopelessness, worthlessness, excessive guilt, and suicidal ideation helps distinguish depression in the context of medical illness.
(17)
Table 5.3.7.3 outlines the medically related risk factors for

(17)
Table 5.3.7.3 outlines the medically related risk factors for 
developing depression: increasing levels of debilitation, advanced disease, and concurrent presence of other chronic illnesses or disabilities. Medications frequently encountered in the oncology setting that contribute to depressive symptoms are corticosteroids (dexamethasone and prednisone), chemotherapeutics (interferon, interleukin-2, vincristine, procarbazine, l-asparaginase), and sup-portive care medications.
(17) Depression may relate to organ failure 
or nutritional, endocrine, and neurologic complications of cancer. Depression is a common symptom of pancreatic cancer, which led to speculation about a tumour-induced mood disturbance medi-ated by alteration of brain serotonergic function through the effect of proinﬂ  ammatory cytokines.
(18–21)
Management . Psychotropic medications are effective in reducing 
depressive symptoms present in cancer patients.(22) Table 5.3.7.4

(18–21)
depressive symptoms present in cancer patients.(22) Table 5.3.7.4 
lists the most frequently used antidepressant medications in patients with cancer and their initial and maintenance doses. The antidepressants commonly used today are SSRIs, mirtazapine, ven-lafaxine, or buproprion. Tricyclic antidepressants and duloxetine are beneﬁ  cial for patients with depressive symptoms and neuro-
pathic pain. Psychostimulants treat depressive symptoms, and counter fatigue related to advanced illness and the somnolence associated with opioids. For depressed cancer patients not expected 
to survive weeks to months, psychostimulants provide more rapid relief from distressing depressive symptoms. Initiating antidepres-sants at low doses for elderly and debilitated patients and titration upward as tolerated provides similar beneﬁ  ts, but over a longer 
period of time.
Suicide and cancer

The incidence of suicide is increased in patients with cancer com-pared with the general population, but it is not as high as is often assumed. Suicide is more likely to occur in advanced disease as depression, hopelessness, and the presence of poorly controlled symptoms (especially pain) escalate.
Evaluation of suicidal thoughts should take into account disease 
stage and prognosis. Almost all patients who receive a diagnosis of cancer, even if the prognosis is optimistic, consider or contemplate suicide in the event of developing unbearable or intolerable distress. Some patients maintain supplies of medications for this purpose. This practice allows the patient to maintain a perception of control over progressive disease and feared intolerable pain and inevitable distress. Maintaining this option sometimes allows patients to tolerate difﬁ  cult treatments.
Morbid preoccupation with suicide or ruminative plans to com mit

Morbid preoccupation with suicide or ruminative plans to com mit 
suicide in cancer patients for whom the disease is in remission or in whom a good prognosis exists require careful evaluation.
(23)
Patients with a poor prognosis, advanced disease, and poorly controlled symptoms often have thoughts of suicide that are more Table 5.3.7.2 Common anxiolytic agents
Drug Brand name Starting dose/day Theraputic 
dose/day
SSRIs Sertraline
 Fluoxetine
 Paroxetine Citalopram
 Escitalopram
Benzodiazepines
 Alprazolam, XR
 Clonazepam, wafers
 *Lorazepam *Diazepam
Hypnotics
 Temazepam Zolpidem
 Zaleplon
 EszopicloneZoloft
Prozac
PaxilCelexa
Lexapro
Xanax
KlonopinAtivan
Valium
Restoril
Ambien
Sonata
Lunesta25–50 mg AM
10–20 mg AM10–20 mg10–20 mg 5–10 mg
0.25–0.5 mg
0.25–0.5 mg2 mg
15 mg
5 mg
5 mg
2 mg50–150 mg
20–60 mg
20–60 mg20–60 mg
10–30 mg
0.5–2.0 mg
0.5–2.0 mg
0.5–2.0 mg
 5–20 mg
15–45 mg
5–20 mg
5–20 mg
2–3 mg

15 mg
5 mg
5 mg
20–60 mg
10–30 mg
0.5–2.0 mg
0.5–2.0 mg
0.5–2.0 mg
 5–20 mg
15–45 mg
5–20 mg
5–20 mg
2–3 mg
* Also IV, IMTable 5.3.7.3  Medical-related risk factors for depression in patients 
with cancer
Poorly controlled pain
Other chronic disease/disability; advanced stage
Medications
 Corticosteroids
  Prednisone, dexamethasone
 Inteferon and Interleukin-2
 Chemotherapeutic agents
  Vincristine, vinblastine, procarbazine, L-asparaginase
Other medications
 Cimetidine
 Indomethacin Levodopa
 Methyldopa
 Pentazocine Phenmetrazine
 Phenobarbital
 Propranolol Rauwolﬁ  a alkaloids
 Tamoxifen
 Antibiotics (Amphotericin B)
Other medical conditions
 Metabolic (anemia; hypercalcemia) Nutritional (B
12 or folate)
 Endocrine (hyper-hypothyroidism; adrenal insufﬁ  ciency)
 Neurologic (paraneoplastic syndrome)
Sites of cancer
 Pancreatic, small cell lung, breast cancer, lymphoma (producing remote 
  CNS effects)

1103
likely to be viewed as rational by physicians.(24) These patients may 
request assistance from a physician in obtaining a prescription for medications to use to commit suicide. A treatable major depressive episode may precipitate their suicidal ideation, so it is particularly important to evaluate for the presence of hopelessness, which is a better predictor of suicidal risk than depression itself.
(23)
Management . Attentiveness to uncontrolled physical symptoms, 
especially pain, is crucial. Adequate pain control may have a dual effect of hastening death, while ameliorating suffering. Most physicians feel comfortable providing comfort and relieving distress. Increasing numbers of physicians do not consider this practice to be assisted suicide but as best medical care geared to maximal comfort.
(25)
Poorly controlled pain in patients with organ failure and meta-
bolic encephalopathy may result in poor judgement and impulse

(25)
bolic encephalopathy may result in poor judgement and impulse 
control leading to unpredictable suicide attempts.(26) These patients 
beneﬁ  t from a 24 h companion, nurse, or family member who 
understands the patient’s compromised state and treatment for delirium.
Delirium
Delirium is a global cerebral dysfunction characterized by a ﬂ  uctu-
ating level of arousal and cognitive disturbances. Symptoms include 
disorientation and confusion, inattention and poor concentration,

disorientation and confusion, inattention and poor concentration, 
perceptual disturbances, disordered thought process, psychomotor agitation or retardation, and an altered sleep–wake cycle. Delirium is distinguished from dementia in part by its reversibility. However, in advanced cancer, as organ failure progresses and results in refrac-tory metabolic derangements, delirium may be irreversible. The primary goal is ensuring the safety of the patient and caregivers. Protecting others from aggressive or combative behaviour is essen-tial. Family members should be told that the cause of the behaviour is brain dysfunction, not a mental aberration, and a given guidance 
in understanding the patient’s states.
In patients with cancer, especially those in advanced stages, an

In patients with cancer, especially those in advanced stages, an 
abrupt shift in mood or behaviour is most often related to a change in neurologic, vascular, or metabolic status; a psychological basis is far less likely. In fact, up to three-fourths of terminally ill patients may develop a delirium before death. Common causes of delirium in cancer are outlined in Table 5.3.7.5.
Management  begins with attention to the patient’s safety. It is 
important to have constant 1:1 observation, preferably by a person who can correct the patient’s misinterpretations of reality. Providing Table 5.3.7.4  Commonly used antidepressants in cancer
Drug Brand name Starting daily dosage PO (mg) Therapeutic daily dosage PO (mg)
Selective serotonin-reuptake inhibitors
 Sertraline Fluoxetine Paroxetine Citalopram
(neuropathic pain management primarily)
 Nortriptyline
 Amitriptyline Desipramine
Other agents
 Venlafaxine Trazodone

Sertraline Fluoxetine Paroxetine Citalopram
 Bupropion (XL, SR)
 Mirtazapine
Psychostimulants
 Methylphenidate
 Modaﬁ  nil Dextroamphetamine(Zoloft)
(Prozac)
(Paxil)(Celexa)
(Lexapro)
(Pamelor)
(Elavil)(Norpramin)
(Effexor)
(Desyrel)
(Wellbutrin, Zyban)
(Remeron)
(Ritalin)
(Provigil)(Dexedrine)25–50 mg AM
10–20 mg AM
10–20 mg AM10–20 mg AM
 5–10 mg
25–50 mg
25–50 mg25–50 mg
18.75–37.5 mg
50–100 mg
50–75 mg
15 mg HS
 5–10 mg (8AM & Noon)
50–100 mg (8AM & Noon) 5–10 mg (8AM &Noon)50–150 mg
20–60 mg
10–20 mg
50–200 mg
50–200 mg50–200 mg
75–225 mg
100–200 mg
150–400 mg
15–45 mg
10–30 mg
100–400 mg
10–20 mg
Lithium and mood stabilizers only for bipolar disorder;
MAOIs not recommended.
Table 5.3.7.5 Common causes of delirium in cancer
Causes Examples
Metabolic encephalopathy
  because of vital organ failure
Electrolyte imbalance

Treatment side effects
Infection
Hematologic abnormalities
Nutritional
Paraneoplastic syndromes
Metastatic or primary brain tumorLiver, kidney, lung (hypoxia), 
  thyroid, adrenal
Sodium, potassium, calcium, glucose
Narcotic/analgesicsAnticholinergics
Phenothiazines
AntihistaminesChemotherapuetic agents
Steroids
Radiation therapy to brainSepticemia
Microcytic and macrocytic anemias, 
  coagulopathies
General malnutrition, thiamine, folic acid, 
  vitamin B
12
Remote effects of tumorsGlioblastoma multiforme, primary CNS
 lymphoma5.3.7 psychiatric aspects of cancer

SECTION 5  psychiatry and medicine 1104
consistent caregivers, structured interactions with others, and 
frequent reorientation may limit the distress experienced by the patient. Elderly patients are more vulnerable to developing 
delirium, and those with cognitive impairment or dementia are at even higher risk. It is preferable to avoid physical restraints. However, containment of severe agitation may temporarily require restraints to prevent removal of endotracheal tubes, intravenous access, and loss of indwelling catheters, and also to avert falls. Behavioural symptoms of delirium in patients with cancer are outlined in Table 5.3.7.6.
Medications commonly used in managing delirium are summa-
rized in Table 5.3.7.7. Identiﬁ  cation and corrections of the underly-

ing aetiology of the delirium is not always possible and in thesecircumstances, neuroleptics providing relief for the patient from distressing symptoms should be the primary intervention. While haloperidol and lorazepam administered in conjunction provide additional sedative effects for patients with sever agitation,
(27)
patients with hypoactive subtype of delirium will beneﬁ  t from the 
administration of neuroleptics for symptomatic relief.(26,28)  In the 
terminal stage of cancer, delirium may be irreversible and refractory to neuroleptics. Additional sedation with alternative agents may be required to provide comfort and safety for the patient and family.Further information
www.apos-society.org
Free online education program for multidisciplinary training in 
Psycho-Oncology. Website contains ﬁ  fteen web-cast lectures in the ﬁ  ve

Psycho-Oncology. Website contains ﬁ  fteen web-cast lectures in the ﬁ  ve 
following tracks: Introduction to oncology, program administration, symptom detection and management (eight web-casts), interventions (four web-casts), and population-speciﬁ  c issues.
Direct link: http://www.apos-society.org/professionals/meetings-ed/
webcasts/webcasts-multidisciplinary.aspx
www.ipos-society.orgFree online lectures: Multilingual core curriculum in psycho-oncology. 
Five web-cast lectures translated into English, French, German, 
Hungarian, Italian, and Spanish.
Direct link: http://www.ipos-society.org/professionals/meetings-ed/
core-curriculum/core-curriculum-pres.htm
Holland, J.C. (2002). History of psycho-oncology: overcoming attitudinal 
and conceptual barriers. Psychosomatic Medicine ,64, 206–21.
Holland, J.C., (ed.) (2006). Quick reference for oncology clinicians: the

Holland, J.C., (ed.) (2006). Quick reference for oncology clinicians: the 
psychiatric and psychological dimensions of symptom management . IPOS 
Press, Charlottesville.
Psycho-oncology: Journal of the American Psychosocial Oncology Society, 
Behavioral and Ethical Aspects of Cancer . Published monthly in hard 
copy and online by John Wiley & Sons, Ltd.
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of cancer and cancer treatment due to a shared biologic mechanism? Cancer ,97, 2919–25.
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than normal interleukin-6 concentrations in cancer patients with 
depression: preliminary ﬁ  ndings. The American Journal of Psychiatry ,
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(ed. J.C. Holland), pp. 509–17. Oxford University Press, New Y ork.

 4. Hewitt, M., Herdman, R., and Holland, J. (eds.) (2004). Meeting 
psychosocial needs of women with breast cancer . Institute of Medicine, 
National Academies Press, Washington, DC.
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self-administered psychosocial cancer screening tool. Cancer Practice ,
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 9. Jacobsen, P .B., Bovbjerg, D.H., Schwartz, M., et al. (1995). Conditioned 
emotional distress in women receiving chemotherapy for breast cancer. 
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10. Andrykowski, M.A. and Redd, W.H. (1987). Longitudinal analysis of 
the development of anticipatory nausea. Journal of Consulting and 
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Handbook of psychiatry in palliative medicine  (eds. H. Chochinov and 
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13. Noyes, R. Jr., Holt, C., and Massie, M. (1998). Anxiety disorders. 
In Psycho-oncology  (ed. J.C. Holland), pp. 548–63. Oxford University, 
New Y ork.Table 5.3.7.7 Medications for managing delirium in cancer patients
Drug Brand name Approximate daily dosage
Neuroleptics
 Haloperidol
 Chlorpromazine
 Risperidone Olanzapine
 Quetiapine
 Lorazepam
 Midazolam*
Anesthetics
 Propofol*Haldol
Thorazine
Risperdal
Zyprexa
Seroquel
Ativan0.5–5 mg every 2–12 h, PO, IV, SC, IM
12.5–50 mg every 4–12 h, PO, IV, IM
1–3 mg every 12 h, PO
2.5–5 mg every 6–8 h, PO
12.5–50 mg every 12 h, PO
0.5–2.0 mg every 1–4 h, PO, IV, IM
30–100 mg every 24 h, IV, SC
10–50 mg every h, IV
PO, orally; IV, intravenously; SC, subcutaneously; IM, intramuscularly.
* Usually IV continuous infusion in intensive care setting.Table 5.3.7.6  Behavioral symptoms of delirium in patients 
State Symptom
Early, mild
Late, severe with

Late, severe with 
 behavioral changesAlteration of sleep-wake cycle, transient periods of 
  d i s o r i e n t a t i o n
Unexplained anxiety and sense of dreadIncreased irritability, anger, temper outbursts
Withdrawal, refusal to talk to staff or relatives
New onset of forgetfulness
Refusal to cooperate with reasonable requests;   pulling out tubes and lines
Angry, swearing, shouting, abusive
Demanding to go home, pacing corridorIllusions (misidentiﬁ  es staff, visual and sensory clues)
Delusions (misinterprets events, usually paranoid, 
  fears of being harmed)
Hallucinations (visual and auditory)

1105
14. Rowland, J.H. (1989). Intrapersonal resources: developmental stage of 
adaptation: adult model. In Handbook of psycho-oncology: psychological 
care of the patient with cancer  (eds. J.C. Holland and J.H. Rowland), 
pp. 25–43. Oxford University Press, New Y ork.
15. Peretz, T., Baider, L., Ever-Hadani, P ., et al. (1994). Psychological 
distress in female cancer patients with holocaust experience. General 
Hospital Psychiatry ,16, 413–18.
16. Roth, A.J. and Holland, J.C. (1994). Treatment of depression in cancer 
patients. Primary Care in Cancer ,14, 23–9.
17. Coups, E., Winell, J., and Holland, J. (2005). Depression in the context 
of cancer. In Biology of depression: from novel insights to therapeutic 
strategies , Vol. 1 (eds. J. Lucinio and W. Ma-LeWong), pp. 365–85. 
Wiley, Weinheim, Germany.
18. Ebrahimi, B., Tucker, S.L., Li, D., et al. (2004). Cytokines in pancreatic 
carcinoma. Cancer ,101, 2727–36.

19. McDaniel, J.S., Musselman, D.L., and Porter, M.R. (1995). Depression 
in cancer: diagnosis, biology and treatment. The Journal of General 
Psychology ,52, 89–99.
20. Lerner, D.M., Stoudemire, A., and Rosenstein, D.L. (2001). Cytokine-
induced neuropsychiatric toxicity. In Cytokine therapeutics in infectious 
diseases  (ed. S.M. Holland), pp. 323–32. Lippincott Williams & Wilkins, 
21. Mussleman, D.L., Lawson, D.H., Gumnick, J.F., et al. (2001). Paroxetine 
for the prevention of depression induced by high-dose interferon alpha. The New England Journal of Medicine ,344, 961–6.
22. Wilson, K., Chochinov, H., de Faye, B., et al. (2000). Diagnosis and 
management of depression in palliative care. In Handbook of psychiatry 
in palliative medicine  (eds. H. Chochinov and W. Breitbart), pp. 25–51. 

23. Rosenfeld, B., Krevo, S., Breitbart, W., et al. (2000). Suicide, assisted 
suicide, and euthanasia in the terminally ill. In Handbook of psychiatry 
in palliative medicine  (eds. H. Chochinov and W. Breitbart), pp. 51–63. 
24. Conwell, Y. and Caine, E.D. (1991). Rational suicide and the right to 
die: reality and myth. The New England Journal of Medicine ,325, 1100.
25. Chochinov, H.M. (2002). Dignity-conserving care- a new model 
for palliative care: helping the patient feel valued. The Journal of the 
American Medical Association ,287, 2253–60.
26. Breitbart, W. and Cohen, K. (1998). Delirium. In Psycho-oncology
(ed. J.C. Holland), pp. 564–75. Oxford University Press, New Y ork.
27. Breitbart, W., Marotta, R., Platt, M., et al. (1996). A double-blind

27. Breitbart, W., Marotta, R., Platt, M., et al. (1996). A double-blind 
trial of haloperidol, chlorpromazine and lorazepam in treatment 
of delirium in hospitalized AIDS patients. The American Journal of 
28. Breitbart, W. (2002). Spirituality and meaning- centered group 
psychotherapy interventions in advanced cancer. Support Care in 
Cancer ,10, 272–80.
5.3.8 Psychiatric aspects 
of accidents, burns, and other physical trauma
Epidemiology of accidents and injury
The one-year prevalence of accidents is about 15–20 per cent with 
highest prevalence in the younger age groups. About 80 per cent of accidents cause personal injury, and 1/3 to 1/2 of these injuries result in medical attention. About 10 per cent of 
medically attended injured victims require hospitalization.
(1)

(1)
In the UK (population about 60 million) 31 845 people were killed or seriously injured in 2006 due to road accidents and there were 2 58 404 road casualties.
Accident occurrence and psychiatric disorders
On a group basis, lower social classes, subjects with less education and lower intelligence tend to sustain more accidents and injuries (and have higher morbidity and mortality in general). The ratio of males to females for both fatal and non-fatal accidents is about 2:1 in subjects below 60 years of age. Individual variables associated with increased liability of being involved in an accident include antisocial tendencies, aggressiveness, impulsiveness, thrill and adventure-seeking behaviour. Conscious or unconscious intention is not an important explanation of the overall prevalence of accidents or injuries in the society.
Patients with signiﬁ  cant psychological problems (psychopathology

Patients with signiﬁ  cant psychological problems (psychopathology 
including substance abuse) sustain more severe injuries than healthy subjects and the prevalence of psychiatric disorders is increased among hospitalized injured adults compared to surgical 
patients admitted for other reasons. At least 15–20 per cent of per-
sons brought to hospital emergency rooms due to accidental injury have clinical significant blood concentrations of alcohol. Furthermore, patients with schizophrenia, affective illness and post-traumatic stress disorder have more accidental deaths  (and 
suicides) compared to the general population.
Physical injuries
Most non-fatal injuries treated in hospitals are minor head concus-sion and lacerations, strains/sprains, contusions/abrasions and fractures to body parts such as limbs. More severe injuries are mostly related to high energy ac cidents (e.g. motor  vehicle accidents)

and often involve both the head and limbs. Injuries to the inner organs are less frequent, but mostly more severe. The anatomical based Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS) are the most widely used classiﬁ  cation system of physical 
injury. Other classiﬁ  cation systems based on physiological impact 
of trauma (e.g. Revised Trauma Score, Glasgow Coma Score) and combinations of anatomical injury and physiological impact (e.g. Trauma and Injury Severity Score) exist as well. See: http://www.trauma.org/archive/scores/ais.html;
Physical injury as psychological trauma
Accidental injury implies several important sources of threat, loss or conﬂ  ict which may cause psychological distress or psychiatric 
disorders. The most important accident related variables associated with subsequent psychological problems include,
◆ Severity of the accident (e.g. real degree of threat to life of one 
self and others)
◆ Degree of helplessness
◆ Duration of the stressor

◆ Presence and type of actual physical injury
◆ Exposure to dead and mutilated bodies.
Nevertheless, pre-accident adjustment, personality and the per-
sonal meaning of the accident or injury are the strongest predictors 5.3.8 psychiatric aspects of accidents, burns, and other physical trauma

SECTION 5  psychiatry and medicine 1106
of both acute psychological responses and long-term psychiatric 
outcome. This observation holds even in the presence of a severe injury,
(2) although the type of injury per se  may inﬂ  uence the short- 
and long-term outcome. The relative contribution of ‘objective’ 
accident related compared to ‘subjective’ appraisal related variables in shaping the acute response varies. A rule of thumb is that the less severe the accident, the more important are variables not directly related to the accident per se  (i.e. the personal meaning of the acci-
dent and its consequences for the individual.
(3) Important individ-
ual variables include,(4–6)
◆ Pre-injury mental health and adjustment problems
◆ Personality traits (e.g. neuroticism, quality of attachment)
◆ Trauma history
The accident per se  may represent a blow to the person’s feeling of

The accident per se  may represent a blow to the person’s feeling of 
invulnerability (narcissistic loss). In some, the accident situation may provoke conﬂ  ictual feelings (e.g. self-blame, survivor guilt) or shame 
(e.g. own actions or fantasies prior to the situation). Injury to the body may threaten self-esteem and body image; or represent a loss of function. In some cases, the injury may even serve as a primary gain in a psychodynamic sense. The immediate responses will also be inﬂ uenced by psychological issues like fear of losing control, or the 
effect of that phenomenon if it occurs. Conﬂ  icts related to secondary 
gains may also inﬂ  uence the clinical response observed by others.
Clinical features and assessment of trauma at the 
accident scene
The ABC rule of assessment (Airway, Blood pressure, Circulation) 
should always be the ﬁ  rst step in any medical assessment of acute

should always be the ﬁ  rst step in any medical assessment of acute 
injury followed by physical examination of the thorax, abdomen, head and ﬁ  nally the extremities. However, except for head injuries 
associated with impaired cognitive function and injuries that signiﬁ  cantly interfere with ventilation or cardiovascular function 
(e.g. agitation due to hypoxia or apathy due to cardiovascular hypotension), the injury it self plays a minor role for the immediate psychological  responses to trauma.
Early and marked psychophysiological arousal symptoms like (in 
decreasing frequency) heartbeat, tremor, dry mouth, restlessness, shaking/trembling, weakness in legs, and sweating are common responses to an acute accident. However, the majority of accident victims appear reasonably calm
(5) although many have some degree

(5) although many have some degree 
of inner turmoil that may impair the ability to receive, retrieve, and handle information. If behavioural disturbances are seen during the ﬁ  rst seconds to minutes, they mimic phylogenetic responses 
known from all mammals exposed to acute and severe stressful events: ﬂ  ight, freeze, or ﬁ  ght.
(a) Flight response (anxiety, panic)
The patient appears frightened, may scream or cry. Clear cut panic 
(e.g. overt confusion, bewildered or aimless behaviour or running away), is rather infrequent even during disasters ( <1 per cent). 
Although lowering of blood pressure is not part of the clinical fea-tures of panic, panic is often included in the concept of ‘shock’ used by lay people and media.
Physiological response to physical injury may be misunderstood 
as ﬂ ight response. Patients with injury to the thorax hyperventilate

as ﬂ ight response. Patients with injury to the thorax hyperventilate 
and may appear anxious and scared. Cyanosis is not a sign of emo-tional distress in adults, and hyperventilation should always be considered as sign of respiratory problems needing urgent medical 
attention (e.g. pneumothorax). Patients with head injury may be confused and bewildered, but they seldom display the open anxiety 
seen in patients who panic.
Panic with severe behavioural disturbances may threaten the safety

of the subject and provoke anxiety in bystanders and other victims who may themselves be afraid to lose control. Thus, whenever possi-ble, patients with strong anxiety or panic should be offered immedi-ate psychological support. Establishing physical (e.g. hand around the shoulder) and verbal contact is important to reduce panic and provide a sense of security and control. Verbal contact may also reveal the subject’s real or imagined fears and provide the subject with an alternative way to express their inner turmoil and despair and thus pave the way for more optimal coping and subsequent behavioural control. The subject should be removed from the accident scene, but not left alone. These subjects need to move around and should not be forcefully immobilized. A helper may walk with the patient until he calms down. The exception to this rule is rare instances where the subject’s behaviour is completely out of control representing an immediate threat to the physical safety of self or

patient until he calms down. The exception to this rule is rare instances where the subject’s behaviour is completely out of control representing an immediate threat to the physical safety of self or others.

Reuniting family members may reduce anxiety and worries.Hyperventilation is treated as usual (breathing into a bag to 
increase the CO
2 -level) combined with physical and verbal contact 
as described above. It is crucial that somatic causes (e.g. pneumot-horax, intoxication) have been ruled out.
(b) Freeze response (apathy)
Freeze responses include halted surprise or in more extreme cases emotional numbness (apathy). Apathy causing lack of appropriate lifesaving activities occur rather infrequently among random sam-ples of accidentally injured adults (less than 10 per cent). In less than 1 per cent, signiﬁ  cant parasympathetic (vagus) responses with

lowering of blood pressure occurs (‘emotional shock’). These patients appear pale and silent. The look of their eyes gives an impression of detached distance, if they were looking onto their own personal world somewhere far away from the actual accident scene. Rarely, an atypical freeze response characterized by blank denial of having sustained an injury when one, in fact, exists may be seen. These subjects may continue to behave as if nothing had hap-pened and not take appropriate precautions at the accident scene.
Several physical injuries may mimic freeze-response. Patients 
with internal bleedings (e.g. liver, spleen) may appear pale and 
silent as if in emotional shock (‘freeze response’). The pulse is weak and fast (tachycardia), however, in contrast to the vagus tonus induced bradycardia of the freeze response.
If there is a risk of further injury associated with remaining at the

If there is a risk of further injury associated with remaining at the 
accident scene, patients with freeze responses must be removed to a safe place. They should not be left alone, but covered with a jacket or a blanket over their shoulders and attended to in a calm and gentle way, encouraging them to express some of their thoughts and emotions. If the freeze response is severe and prolonged, the patient should be brought to an emergency room for renewed and extended medical evaluation and basic psychological care. Cases of complete denial of having sustained an injury despite evidence for the opposite, should clinically be handled as a freeze response.
(c) Dissociative symptoms
Dissociative symptoms occur in about 15 per cent during the 1st second to minutes after an accident and may be associated with

1107
ﬂ ight or freeze responses. Brief symptoms of derealization are most 
common, even in relatively minor accidents (e.g. ‘unreal’ , like a ‘dream’ or ‘slow movie’). Symptoms of depersonalization (e.g. ‘I watched my body burn from a distance’) are less common and usually signal a more severe psychological response. Brief symp-toms of dissociation do not predict later psychiatric problems,
(5,7,8)
but marked and prolonged dissociative symptoms still present weeks after the accident.
(7)
(d) Fight response (aggression)

(5,7,8)
(7)
Fight responses include irritability, anger and more rarely, open aggression. This response is most often seen among bystanders or helpers who feel threatened by the exposure of dead and mutilated bodies. They may quarrel with the rescue team, and sometimes even interfere with the work of police or helpers. Open aggression is rare among victims themselves with the exception of intoxicated victims with severe personality disorders and a few who have sustained severe head injuries (e.g. subdural hematoma, fron-tal brain contusion).
Irritability and aggressive comments should not be taken per-

sonally by the helpers, but interpreted a symptom of helplessness. In most cases, this response is psychological, but impaired behav-ioural control due to drug or alcohol may be contributing factors. The patient should be treated as being extremely anxious and under high emotional distress. Reuniting with family or signiﬁ  cant others 
if possible may be helpful. Physical activity may reduce aggression. If suitable, simple tasks which require physical movements may be therapeutic (‘Can you give me a hand with . . . . .’), but subjects under stress should never be involved in important rescue tasks due to their impaired judgement ability and tendency to act irrationally.
(e) Acute stress reaction
Marked or severe ﬂ  ight, freeze or ﬁ  ght reponses are included in the 
ICD-10 (F43.0) deﬁ  nition of acute stress reaction (ASR). ASR is 
deﬁ ned as immediate onset of marked psychological symptoms

deﬁ ned as immediate onset of marked psychological symptoms 
(within 1 hour) following exposure to an exceptional mental or physical stressor. The symptoms must begin to decrease after 8 hours if the stressor is transient (e.g. accident). If exposure to the stress continues (e.g. combat zone, hostage situation) the symp-toms must begin to diminish after 48 hours. In contrast, the DSM-IV concept ‘acute stress disorder’ (ASD) describes develop-ment of symptoms not earlier than 2 days after the trauma but within one month after exposure.
Psychotropic drugs are seldom needed to treat acute psychologi-
cal responses at the accident scene if proper medical care including emotional contact from skilled, empathic helpers is offered. 
Violence towards victims having lost behavioural control may 
increase the anxiety among other victims and bystanders, and in

increase the anxiety among other victims and bystanders, and in 
fact, increase the risk for more behavioural disturbance within the group, and should thus be avoided.
(f) Acute pain
Some injured persons do not report pain complaints during the 1st second to minutes after even severe physical injury, and some may even continue to perform tasks as usual. This response occurs particularly in situations with continous threat to others or own life (e.g. wounded soldiers). This is part of a brief dissociative response which may be life saving and does not reﬂ  ect psychopa-
thology. However, a few accident victims respond differently. They may report the most painful physical sensations ever experi-
enced. In the absence of severe physical injury, this response most often reﬂ  ects catastrophic cognitions associated with severe anxie-
ty
(5) and should be treated accordingly. Most injured patients

ty
(5) and should be treated accordingly. Most injured patients 
report some degree of pain as minutes pass, however.
Severe pain should be treated at the accident scene and will con-
tribute to psychological and physical recovery from the injury.(9)
Anxiety and fear may lead to increased pain complaints, so may imagined (!) severe injuries. For those reasons, it is important not only to examine the presence of actual injury, but also explicitly ask the victim if he or she believes or fears  having sustained serious or

life-threatening injuries not detected by the medical personnel. If yes, factual information combined with additional proper medical examination if needed, should be provided to reduce the subject’s fears and worries. Faced with true life-threatening injuries, the helper should admit facts if asked, but nevertheless provide some hope and cautioned optimism. It is often hard to evaluate true prognosis at the accident scene and advanced trauma surgery may save the life of many severely injured subjects who would have died a few decades ago.
Responses seen in the emergency room
In urban areas, most subjects will be brought to emergency rooms within less than an hour. At that time most victims have started the process of working through the accident, the injury and its implications. This process is reﬂ  ected in a characteristic cluster of 
emotions, cognitions and physiological symptoms observed in humans exposed to all types of stressful situations.
(10–12)

(10–12)
◆ Intrusion includes images of the accident popping into the 
victims mind, and thinking about the accident even when the person do not want to do so. The main load of intrusive symp-toms are related to the severity of the accident and the personal meaning. Intrusive symptoms are common both in post-traumatic depression and anxiety.
(5)
◆ Avoidance includes trying not to talk about the accident or 
avoiding any cognitive or behavioural activities which reminds the person about the accident. Such symptoms and signs are strongly related to accident-independent variables such as per-sonality traits (e.g. coping style) and more often associated with anxiety than depression.
(5)
◆ Hyperarousal includes startle response, strongly increased heart 
rate, shivering and trembling, irritability, difﬁ  culty in concentrat-

(5)
ing, hypervigilance and disturbed sleep. With the exception of difﬁ culty to sleep, clinically signiﬁ  cant hyperarousal is rather 
infrequent in randomly selected accidentally injured subjects (less than 10 per cent). However, severe hyperarousal signiﬁ  es a strong 
physiological and emotional response and is increased among injured compared to non-injured accident victims and is in some studies associated with later post-traumatic distress problems.
(13)
The three most common types of behavioural problems seen in 
the emergency room are,
◆ Uncontrolled crying or screaming
◆ Strong anxiety which may include excessive pain complaints
◆ Aggression and dyssocial behaviour
Crying and anxiety are associated with high levels of intrusion

Crying and anxiety are associated with high levels of intrusion 
and avoidance, and may be part of ASR. Systematic and carefully 5.3.8 psychiatric aspects of accidents, burns, and other physical trauma

SECTION 5  psychiatry and medicine 1108
conducted medical examinations accompanied by supporting 
questions about the patients emotions, thoughts, and fantasies are the most effective way to put the patient at ease. Sedating drugs are seldom needed if the necessary psychological support is provided. Separation from family members or signiﬁ  cant others may increase 
anxiety and despair, and family reunion may be helpful. If symp-toms of high arousal persist, prazosin, a central nervous system (CNS) active alpha-1 adrenoreceptor antagonist or a beta-blocker (e.g. 40–60 mg propranolol) or alfa—may be given to attenuate extreme adrenergic tonus.
(14)
Aggressive behaviour occurs in about 5 per cent of injured 
persons brought to hospital, mostly among intoxicated subjects. The presence of head injury must be ruled out. Most cases can be brought under control with the help of signiﬁ  cant others and ﬁ  rm,

persons brought to hospital, mostly among intoxicated subjects. The presence of head injury must be ruled out. Most cases can be brought under control with the help of signiﬁ  cant others and ﬁ  rm, 
but calm attitude, addressing the fear or helplessness. In a few cases, acute administration of benzodiazepines or a sedating neuroleptic may be necessary. If the patient is intoxicated or suffer from respi-ration difﬁ  culties, neuroleptics may be the safest option. In cases of 
armed patients, the necessary precautions must be taken.
Psychotic forms of ASR are seldom seen in injured adults and 
even patients with schizophrenia or other psychotic disorder prior to the accident appear remarkably calm and collected upon arrival in the hospital. If psychosis is present at arrival in the emergency room, inﬂ  uence of psychoactive substances, severe injury (e.g. 
brain injury, respiratory failure) or a concurrent psychotic disorder 
must be ruled out.
(a) Whiplash injury

Rear end collision may cause a whiplash like movement of the neck. Biomechanical studies suggest overstretch of cervical facet-joint capsules as a possible source of pain. Neck pain, stiffness or tender-ness may occur minutes to hours after the accident. A medical examination including an X-ray of the cervical columna seldom reveals pathological ﬁ  ndings (Quebec classiﬁ  cation grade I). In more 
severe cases, distortion and minor bleeding in capsules, ligaments, tendons or muscles (grade II) may lead to additional musculoskel-etal signs such as decreased range of motion and point tenderness. In severe injuries, neurological ﬁ  ndings (impaired myostatic reﬂ  ex-

es, pareses, loss of sensibility, grade III) or even fractures (grade IV) may be present. In patients with whiplash related injury grade I or II, acute psychological distress and associated neck pain is the most important predictor of long-term outcome.
In the emergency room, treatment should aim at providing the sub-
ject with adequate information about the good prognosis. Pain after whiplash-injury usually lasts for four-to-six weeks (!), but gradually disappears. In cases of pain without somatic ﬁ  ndings, pain killers or 
antiﬂ  ogistic medication have uncertain effect and should not be pre-
scribed for more than a week. Sick leave should be avoided or be as short as possible. Mobilization and early return to work is recom-mended. Overtreatment by physicians or physiotherapists (e.g. appli-cation of stiff collar despite no ﬁ  ndings of injury to the cervical colum-
na) may lead to permanent illness behaviour and pain-ﬁ  xation.
(15)

(15)
The optimal physical treatment of whiplash injury is still unsettled,(16)
but premorbid pain and psychiatric disorders represent a risk for 
development of chronic disabling symptoms and should be treated.
(b) Signiﬁ  cant others’ needs
Relatives or survivors may want to see dead signiﬁ  cant others 
brought to hospital, and touch them. This process helps the relatives to work through the traumatic event and should be 
encouraged. If the dead body is grotesquely disﬁ  gured, the most

encouraged. If the dead body is grotesquely disﬁ  gured, the most 
horrifying parts should be covered prior to exposure. In any case, a physician or a skilled nurse should accompany the relatives during exposure. Small childrens’ emotional response to dead bodies mirror the adults’ response. Accordingly, reducing the anxiety and fear of the adults is the best way to help children cope with dead ones. Correspondingly, in cases of severe anxiety in accompanying small children, addressing the helplessness and anxiety of the parents is important. If dead bodies are stored in hospital chapels, care must be taken to cover the presence of religious symbols incongruent to the religious status of the dead one and his family (e.g. Christian crosses should be covered in case of a Jew or a Muslim). The reader is referred to chapter 4.16 for more informa-tion on culture speciﬁ  c responses to stress and trauma.
In disaster situations, the need for information varies among

In disaster situations, the need for information varies among 
relatives, depending on whether their loved ones are missing, injured, or dead (survivor status). Those who have lost loved ones often want to talk to rescuers or get information with regard to any hint about the emotional status of the dead one at the time of death. Accordingly, in situations with several hundred relatives come to the hospital, information is provided in separate groups 
according to the signiﬁ  cant other survivor status. The logistics of 
such procedures should be outlined in the hospital’s disaster plan.
Psychiatric treatment during hospital stay
Most studies indicate that risk factors, emotional, and behavioural responses correspond to that of medically ill patients and identify-ing those who are at increased risk can follow the same guidelines as for medicine in general.
(17) Some patients may complain about

(17) Some patients may complain about 
physical symptoms suggesting undetected injury. Such complaints may in fact be true. If not addressed and attended to, psychological distress presented by means of somatic complaints or symptoms is the rule.
Clinical syndromes requiring psychiatric attention during hospi-
tal stay are listed in Table 5.3.8.1. Complete denial of severity of injury or avoidant coping is maladaptive and should be counter-acted.
(18) Relatives or signiﬁ  cant others should be contacted. They 
may convey unrealistic fears—or hopes (e.g. ‘you will be able to walk’—attitudes in patients with permanent paralysis of legs)— which strongly inﬂ  uence the behaviour and emotional well-being 
of the patient. They may also provide information which may be helpful to understand current behaviour (e.g. previous dysfunc-tion, ‘silent’ delirium undetected by staff).
(a) Anxiety and acute stress reaction

Worrying and compulsive thoughts about the accident or the injury (intrusion) is seen both in anxiety and depression. Extreme anxiety may infrequently lead to cardiovascular complications (e.g. pulmonary embolia) in subjects with cardiovascular risk fac-tors (e.g. elderly subjects often smokers with hypertension and arterosclerosis).
Sleep problems may be present or related to physical pain and 
treatment procedures. The aetiology of nightmares following trau-matic injury is complex.
(19)They mostly emerge a couple of days 
after the accident and disappear gradually. Persisting nightmares for more than two weeks without any signs of mastery in the dream content, suggest development of post-traumatic stress disorder and should thus be treated.

1109
Psychological interventions should be based on clear indication 
and be brief, distress focused and time limited. Symptoms of intru-sion including nightmares may be treated by simple psychological techniques. If one speciﬁ  c traumatic event which can be delineated 
(e.g. visual image of a traumatic moment), psychological video replay techniques (VRT) may be useful. The subject is taught how to relax. Subsequently, the subject reviews the pre-accident and accident situation on an imagined (i.e. mental) video screen. When the anxiety rises to unacceptable levels, the subject is asked to push the (imagined) stop button and press fast replay until a pre-accident situation where the subjects is at ease is reached. When calm, the procedure is repeated, until the subject can view the whole accident without strong anxiety.
If the anxiety level is high or the traumatic event is more 
complex, more comprehensive interventions are needed, e.g. Eye

complex, more comprehensive interventions are needed, e.g. Eye 
Movement Desensitization and Reprocessing (EMDR) or Trauma-
Focused Cognitive Behavioural Therapy (TF-CBT).
(20) If strong 
anxiety is not brought under control by means of psychotherapy or other behavioural techniques (e.g. applied relaxation), psychoac-tive drugs can be added. In injured patients with childhood trauma or other traumatic events in the past, a selective serotonin reuptake inhibitor (SSRI) probably should be the first choice. Sleep problems are best dealt with by environmental adjustment when-ever possible, or by optimal pain control if appropiate. Sedative drugs are secondary option. Mianserin or mirtazapine combine 
sedative and antidepressant effects and may be alternative to benzodiazepines.
Acute stress disorder (ASD) may be conceptualized as an acute 
form of PTSD and may predict chronic PTSD.
(21)The main treat-

ment is psychotherapy (i.e. EMDR, TF-CBT). In PTSD, prazosin reduces nightmares and sleep disturbance in placebo-controlled studies, and may thus be an option also during the ﬁ  rst days to 
weeks after trauma. Some studies have reported propranolol given within days following a traumatic event to be useful for mitigating PTSD symptoms or perhaps even preventing the development of PTSD. The mechanism is thought to be explained by reduced con-solidation of emotional memory. Small doses of glucocorticoids may reduce traumatic memories in ASD as well,
(22)but larger 
controlled studies are needed to verify this ﬁ  nding. Benzodiazepines

controlled studies are needed to verify this ﬁ  nding. Benzodiazepines 
may also reduce acute distress, but may not reduce the risk of 6-month psychiatric anxiety problems. In conclusion, all psychop-harmacological treatments must be provided together with psy-chological interventions addressing the key psychological sources of distress and worry.
(b) Depression
Depressed mood during the first days to weeks following an accident are mostly due to guilt, shame, or grief due to real or Table 5.3.8.1  The most frequently seen psychiatric syndromes during hospital stay following accidental injury
Type of syndrome or clinical 
problemClinical symptoms and  signs Comment
Delirium Confused, strange behaviour; episodic 
disorientation; irritability; episodic fearful lookMay occur without obvious signs of agitation if sedated;
Relatives may detect it and be upset. Diagnosis: ‘Draw a clock test’ helpful

Relatives may detect it and be upset. Diagnosis: ‘Draw a clock test’ helpful 
Abstinence from drug or alcohol increased pulse; sweating; tremor; insomnia; 
agitation; anxiety; nausea; abdominal pain; 
dysphoric.May be interpreted falsely as accident-provoked anxiety
Antisocial personality, histrionic or 
borderline personality disorderAggressive behaviour; poor compliance with 
treatment; abusive language; high demand for 
analgesicsUndetected brain dysfunction must be ruled out; Relatives may provide 
important pre-injury information
Hypomanic or manic responses Elated mood; emotions do not correspond to 
the situation; uncritical behaviour Undetected brain dysfunction; bipolar disorder or hypomanic response as 
a defence against survivor guilt
Anxiety Tense, anxious, restless, worrying, increased 
startle reﬂ  exes; insomnia; dissociative symptoms

startle reﬂ  exes; insomnia; dissociative symptoms 
may occur.Prolonged or delayed stress response or disorder; imagined or real threat 
from accident or injury; physical complication (e.g. hypoxia, delirium); 
abstinent or side effects of drug. Obsessive-compulsive traits and high 
inner tension with fear of losing emotional control. If  unexplained, consult relatives for psychological clues. 
Depression Withdrawn, loss of appetite; inability to feel; sad; 
worrying; passive; lassitude;  anxiety symptoms 
frequentGrief; survivor guilt; psychological response to disﬁ  gurement or loss 
(real or imagined) of function or self-esteem; reactivating of previous 
painful memories 
Medically unexplained 
physiological events including  
delayed healing of woundsRare phenomena; typical senior physicians 
statement  ‘I’ve never seen something like it

statement  ‘I’ve never seen something like it 
before’Secondary gain by extended hospital stay (e.g. alternative prison); factitious 
disorder; extreme stress (psychophysiological activation) 
Excessive pain Complaints of pain; poor sleep and appetite; 
poor performance; do not reveal emotions. Undetected physical  complication; insufﬁ  cient pain treatment; anxiety  or 
depression response in past with obsessive-compulsive traits; withdrawal 
syndrome; drug abuser.
Partial or complete denial of actual 
injuryAs-if-nothing-has-happened behaviour; refuse 
treatment; request early dismissal from hospitalUndetected brain dysfunction; psyc hotic disorder. If male and partial 
denial, consider obsessive-compulsive traits and high inner tension with fear of passivity5.3.8 psychiatric aspects of accidents, burns, and other physical trauma

SECTION 5  psychiatry and medicine 1110
imagined losses. The key to understanding the response is the 
meaning of the accident or the injury for the patient. Guilt, shame or rumination over real or imagined losses is associated with long-term problems
(23) and may require speciﬁ  c therapy.(24)Premorbid 
causes of depression (e.g. bereavement, mood disorder at the time 
of the accident), must be kept in mind. In patients with immobiliz-ing injuries staying in hospital for an extended period, some degree of depressive symptoms is the rule. If the symptomatology is severe and persistent, antidepressants are indicated.
Persisting depression has been found to be highly predictive of a

Persisting depression has been found to be highly predictive of a 
long-term psychiatric consequence, and moderate to severe depres-sion predicts less likeliness of returning to preaccident functional level. Thus, depression should always be taken seriously. If marked depression presist for more then 2–3 weeks, an antidepressant should be given. Due to lower incidence of side effects, the newer low-toxic antidepressants are preferred. Delirinm and abstinence are treated as usual. Detailed presentations of the psychopharma-cology of the injured or medically ill are available.
(34–36)
(c) Pain
Both the injury itself (e.g. burn injuries, injuries to the pelvis, penetrating traumas) or medical treatment (e.g. physiotherapy to prevent contractures, ICU) may be associated with psychological distress and pain.
(25,26)  Pre-accident psychopathology increases the

(25,26)  Pre-accident psychopathology increases the 
prevalence and severity of pain complaints. Pain or fear of bringing about pain leads to diminished movement, which can engender contractures, muscle atrophy, and bed ulcers. Traumatic amputa-tion may be associated with phantom pain and exacerbation of pain in response to imagined movements has been reported in sub-jects with spinal cord injury.
(27)Poorly treated pain can be demor-
alizing to patients and provoke psychological regression, giving-up responses and long-t erm psychiatric problems
(28) including 
increased risk for suicide.(29) Thus active pain control is crucial 
and may reduce the prevalence of long-term suffering.(30) 
Comprehensive reviews of the psychological care of burned sub-jects are available.
(31)
Concerns that trauma patients with injury related pain will 
become addicted if treated properly with analgesics is neither supported by clinical experience nor by empirical data.
(32)However,

(31)
(32)However, 
co-morbid psychiatric disoders must be taken into account when treating injury-associated pain. Patients with a history of substance abuse may have greater tolerance to analgesics and will have to be titrated to higher doses.
(33)
(d) Confusion and psychoses
In civilian life situations, confusion or psychotic responses appear-ing for the ﬁ  rst time days after being admitted to hospital are almost 
exclusively due to a central nervous system dysfunction. Risk factors are severe injuries (ISS >15; third degree burn injury) and 
major head injuries (e.g. contusion). Impaired cognitive functions or drug or alcohol abuse prior to accident and age >50 increase the 
risk of organic mental dysfunction.
In a few cases, psychotic-like confusional and agitated responses

In a few cases, psychotic-like confusional and agitated responses 
occurring during the hospital stay may be due to abrupt disruption of intake of psychotropic medication taken for long periods prior to the accident. If in doubt about the aetiology of a psychotic response seen during the ﬁ  rst days to weeks (including severe manic 
episodes), the psychiatrist should consider the response to be of organic origin and explore the pathophysiological processes as done in cases of delirium. Asking the patient to draw a clock, may 
be a simple and effective way of detecting organic dysfunction.
(37)
(e) Alcohol and drug abuse
A signiﬁ  cant number of accident victims brought to hospital have 
an alcohol or drug problem, and symptoms of abstinence may be misinterpreted as psychological anxiety.
(38)In cases of grossly

(38)In cases of grossly 
deviant behaviour, the presence of co-morbid severe personality disorder should be considered. Alternative explanations include delirium or side effects to drugs (e.g. steroids).
(f) Psychological needs of rescue personnel and staff
Debrieﬁ  ng is a psychological treatment intended to reduce the psy-
chological morbidity that may arise after exposure to accident or injury. Debriefing involves promoting emotional processing/catharsis or ventilation by systematically encouraging recollection/ ventilation/ reworking of the traumatic event. There is no evidence that this method reduces the incidence of post-accident problems in civilian life.
(20,39)  Accordingly, psychiatric intervention in the 
emergency room should be limited to those who display acute and 
severe psychiatric disorders.

Rescue personnel and medical staff may be psychologically 
affected by sudden exposure to grotesquely mutilated bodies.(40)
The same individual vulnerability found in injured subjects apply. Group debrieﬁ  ng has been recommended if the rescue 
operation was extremely difﬁ  cult; there were many dead or there 
was explicit harsh critique of the rescue operation from the media. Debrieﬁ  ng offered and conducted by a respected senior member 
of the rescue team is probably more appropriate than debrieﬁ  ng 
offered by psychologists or psychiatrists. However, empirical data regarding efﬁ  cacy of emotionally focused group debrieﬁ  ng is 
scarce.
Long-term behavioural and psychiatric consequences 
of physical trauma
Physical injury may cause permanent physical change including

scarce.
Physical injury may cause permanent physical change including 
neurological dysfunction,(41) impaired physical function, changes 
in perceived somatic health including pain,(30)decreased capacity 
to work (in children: play), decreased social contact and decreased leisure pleasure.
(42) In an unselected population of hospitalized 
accidentally injured adults, about half will report some complaints three years later. Among those with most severe injuries (ISS >15), 
only 1/3 will have made full recovery after three years, and about half will report at least moderate disabilities.
(43)
The prevalence of non-organic mental disorders among hospi-
talized adults is about 20 per cent after six months and 10 per cent after two years.
(29, 44–49) Depressive symptoms and disorder are 
most frequently seen followed by speciﬁ  c accident-related phobia

most frequently seen followed by speciﬁ  c accident-related phobia 
and PTSD. Subsyndromal PTSD-cases must be added to these numbers. PTSD is associated with several physical health problems including cardiovascular diseases, respiratory diseases, chronic pain conditions, gastrointestinal illnesses, and cancer.
(12) The prev-
alence of alcohol and drug abuse is increased as well.
The prevalence of long-term psychiatric is increased in injuries 
associated with visual disﬁ  gurement, loss of body parts or physical 
function (e.g. spinal cord injury), neck injuries and injuries to the pelvis and genital areas.
(42) Chronic pain following accidental injury 
is often associated with concommittant mental disorders, in par-ticular mood disorders or PTSD.
(50) Man-made accidental injury

1111
(e.g. assault, combat, rape, terrorism) cause more long-term mental 
problems than other types of accidental injury (e.g. natural disasters). Studies comparing outcomes in men versus women  have 
been mixed. Current evidence suggests that women are at higher risk for anxiety and depression, and men are more at risk for substance abuse and antisocial behaviour.
Following extreme psychological and physical trauma (e.g. tor-
ture, concentration camp survivors, hostage situations), permanent change in the person’s pattern of perceiving, relating to, and thinkingabout the environment and the self may occur (ICD-10 F62.0: Enduring personality change after catastrophic experience). The changes should not fully be explained by the presence of PTSD. This diagnostic category does not exist in the DSM-IV .
Assessment of long-term psychiatric consequences of 
traumatic injury
The following key-points need to be explored when evaluating 
long-term effects of traumatic injury

◆ Social and cognitive resources (including social support)
◆ History of mental disorder, social dysfunction or trauma in the 
past
◆ Overlooked physical injury (increased risk if high energy 
accident or severe injury, e.g. undetected frontal brain damage or other neurological injury)
◆ Deviant behaviour or accident-related psychiatric disorders 
following the accident (including ASR or ASD)
◆ Painful treatment procedures
◆ Accident-independent traumatic life-events during the post-
injury period
◆ Current psychiatric disorders
Patients, relatives and physicians may evaluate long-term 
problems differently(51) and psychiatric co-morbidity is prevalent.

problems differently(51) and psychiatric co-morbidity is prevalent. 
Thus the clinical assessment should be supplemented by a system-atic screening for the most common psychiatric disorders (e.g. MINI neuropsychiatric interview) and cognitive, behavioural and quality-of-life issues (e.g. Impact of Event scale, General Health Questionnaire). Questionnaires specifically designed to address physical, emotional and social outcome of accidental injury are available.
(42) A proper, complaint-focused medical 
examination is often necessary as well.(52) The psychiatrist may 
improve the quality of the medical examination by providing the examining physician with speciﬁ  c diagnostic questions based 
on information of the patient’s trauma history and symptom complaints.
Treatment of long-term problems

Psychiatric disorders occurring in the aftermath of injury are treated according to general treatment guidelines of mental disor-ders with some modiﬁ  cations. EMDR and TF-CBT are the best 
validated psychotherapeutic interventions for trauma related PTSD.
(20)If the psychological themes are related to conﬂ  icts, family 
issues or secondary events, short-term psychotherapy as outlined by Horowitz and his group
(10) may be conducted. Body-focused 
treatments may be helpful in some subjects with chronic pain problems after trauma.
(53) Randomized controlled treatment trials of accidentally injured adults with post-injury psychosomatic and 
psychiatric problems are few, however. Comprehensive treatment of patients may provide better results than intervention performed by one single professional only.
(54)
Antidepressants should be given in cases of mood disorders or

(54)
Antidepressants should be given in cases of mood disorders or 
PTSD not responding to psychotherapeutic interventions alone. SSRIs and related drugs are ﬁ  rst choice. Drugs acting on nor-adrenalin 
reuptake alone (e.g. atomoxetine, reboxetin) may increase anxiety and should be avoided. Psychopharmacological treatment of somatoform pain disorders should target both serotonin and nor-adrenalin (e.g. amitryptyline, chlomipramine, duloxetine, venla-faxine). In cases of chronic PTSD with high level of intrusive symptoms, prazosin or propranolol may be added. Betablockers may be valuable as a supplement to anxiety provoking exposure therapy. Benzodiazepines may reduce PTSD-related anxiety, but differences in modulation of skin conductance compared to patients with panic disorder support clinical experience that drug treatment should be supplemented with psychological interven-tions in order to achieve optimal results. Guidelines for psychop-

harmacological treatment in patients with co-morbid physical 
disorders exist (e.g.
(36)).
Compensation claims and litigation
Most accidentally injured subjects do not exaggerate their loss,(55)
and in non-litigant situations malingering is an unlikely explana-tion in most cases of chronic disturbances after accidents. Neither is economical settlement followed by signiﬁ  cant change in clinical 
situation in most cases. However, in litigation situations, the patient’s problem report may sometimes be exaggerated or even invalid. Studies of personal injury plaintiffs indicate that a sig-niﬁ cant number report pre-injury functioning superior to that 
of controls, and malingering has been estimated to 20–30 per cent.
Studies consistently show that delayed-onset PTSD in the absence 
of any prior symptoms is rare, whereas delayed onsets that represent exacerbations or reactivations of prior symptoms may occur.
(56)Untrained subjects are able to endorse symptoms on

(56)Untrained subjects are able to endorse symptoms on 
checklists to meet criteria for diagnoses of major depression, PTSD and GAD, and PTSD self-report measures cannot be used for diagnosis.
(57)Furthermore, intrusive symptoms are not PTSD-
speciﬁ  c and may be signiﬁ  cant in depression as well.(5)This fact 
is often neglected which explains why some expert testimonies misinterpret depression as being PTSD.
The physician should always try to get patient-independent 
information from reliable sources (e.g. medical records, general practitioners) also related to pre-injury function
(58) before 
concluding about long-term problems due to physical injury. The possibility that clinically signiﬁ  cant brain injury or non-injury

concluding about long-term problems due to physical injury. The possibility that clinically signiﬁ  cant brain injury or non-injury 
related illnesses or psychiatric disorders occurring after the injury, have been overlooked during the medical evaluation part of litiga-tion and compensation cases must be kept in mind.
There is no evidence that physical injury provoke de novo
bipolar disorder or disorganized schizophrenia, even among severely maltreated subjects.
(59)However, permanent injury to 
frontal and temporal lobes of the brain may provoke manic episodes, paranoid psychoses with schizophrenic-like symptoma-tology and chronic depression. Both in clinical and court settings, such brain dys functions may be overlooked due to lack of classical neurological signs.5.3.8 psychiatric aspects of accidents, burns, and other physical trauma

SECTION 5  psychiatry and medicine 1112
Expert testimony should be based on the best available evidence 
and standards of care, which requires that experts stay current in their ﬁ  eld of expertise, and revise old opinions as new information 
is published. Personal experience alone is rarely sufﬁ  cient. The psy-
chological difﬁ  culties and challenges faced by an expert witness is 
discussed elsewhere.
(60)
Web links
Physical injury scoring systems
This web link provides access to description and on-line calculation of 
physical injury trauma scores and links to other resources about physical trauma.
http://www.trauma.org/archive/scores/ais.html
Psychiatric treatment
Several databases providing information about treatment in medicine, 
including psychiatry and psychosomatic medicine are available. These databases include systematic reviews metaanalysis, clinical trials, and more, including both psychological and biological 
interventions.
The Cochrane Library

http://www3.interscience.wiley.com/cgi-bin/mrwhome/106568753/HOME
NICE (National Institute for Health and Clinical Excellence):
http://www.nice.org.uk/).
The limitation of such databases is infrequent updates. In areas
with limited research, the conclusions reported may be outdated
even shortly after they are published. Thus these databases
cannot replace continuous updates from databases of original research like:
PubMed http://www.ncbi.nlm.nih.gov/sites/entrez
PsychInfo.http://www.apa.org/psycinfo/
or National center for post-traumatic stress disorder database with 
information about treatment of PTSD and traumatic stress for Mental Health Care Providers. http://www.ncptsd.va.gov/ncmain/index.jsp
Other useful web links
Practice guidelines for psychiatric consultation in the general medical 
settings provided by the
Academy of Psychosomatic Medicine: http://www.apm.org/prac-gui/psy
39-s8.shtml

The European association for consultation-liaison psychiatry and 
psychosomatics publishes power-point presentations about different aspects of psychiatry in the medical ill or injured: http://www.eaclpp.org/
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Law,33(1), 55–8.5.3.8 psychiatric aspects of accidents, burns, and other physical trauma

This chapter covers the psychiatry of menstruation, various mani-
festations of the desire for children (such as surrogate pregnancy and pseudocyesis), pregnancy and mental health, the psychopa-thology of parturition, infant loss, postpartum psychiatric disorders, the mother–infant relationship and infanticide.
The psychiatry of menstruation
It has long been realized that menstruation and mental illness are linked. As early as 1827 menstrual mood disorder was used as a defence in ﬁ  licide.
(1) In the 1850s, Brière de Boismont(2) and 
Schlager(3) carried out the ﬁ  rst surveys showing that 20–30 per cent 
of women suffered a mood disorder before or during the menses—usually irritability or depression, occasionally euphoria. There are descriptions of a wide variety of deviant behaviours, including nymphomania, food cravings, binge drinking, pathological lying, 
shoplifting, and ﬁ  re-setting, as well as suicide, violence, homicide,

shoplifting, and ﬁ  re-setting, as well as suicide, violence, homicide, 
and morbid jealousy. There are other nervous diseases associated with menstruation, including epilepsy, migraine, and hypersomnia.
Recently, there has been much research into the biological basis 
and treatment of ‘premenstrual tension’ (or its synonyms). A num-ber of daily rating schedules have been published, but self-devised rating scales, tailored to an individual patient’s symptoms, can be used, provided that they are carefully completed every day. Scientiﬁ  c 
studies are bedevilled by difﬁ  culties in deﬁ  ning the disorders.
(4)
It is not known whether this is one syndrome or many. Irritability 
is striking, but otherwise the symptoms are common to many other disorders.
Although little is known about the aetiology, progress has been 
made in treatment. There may be a response to serotonin-reuptake-inhibiting antidepressants (e.g. ﬂ  uoxetine, chlomipramine). In so

made in treatment. There may be a response to serotonin-reuptake-inhibiting antidepressants (e.g. ﬂ  uoxetine, chlomipramine). In so 
far as a luteal-phase defect may be a factor, ovulation-promoting drugs such as clomiphene can be tried. The synthetic steroid dan-azol, and the gonadorelin agonists (which suppress menstruation), are draconian treatments for severe cases. All interventions should be prescribed in the context of a long-term study using daily ratings.
Rarely, menstruation is linked to a psychosis with acute onset, 
brief duration, and full recovery. Premenstrual, catamenial, para-menstrual, mid-cycle, and ‘epochal’ variants have been described.

(5)Menstrual psychosis is rare, but perhaps not excessively so. There is a clustering of episodes around puberty and after childbirth, although only a small proportion of menstrual cycles are involved. There are sufﬁ  cient case reports from Japan, India, and Islamic 
countries to suggest a worldwide disorder. This is not a speciﬁ  c 
entity, and most typical examples manifest non-menstrual bipolar disorder at another stage of life. Clinically, it resembles puerperal psychosis. The close relationship between these two psychoses is emphasized by women who develop puerperal and menstrual psychosis at different times.
(6) A Japanese investigation showed an 
association with anovulatory cycles.(7) Pregnancy has a beneﬁ  cial

association with anovulatory cycles.(7) Pregnancy has a beneﬁ  cial 
effect, and there are claims of successful treatment with oral con-traceptives, progesterone, clomiphene, danazol, and gonadorelins. The basis for intervention is a long-term study, with a good base-line and exact timing of events in relation to the menstrual cycle.
Infertility

Motherhood is among the strongest and most universal of motiva-tions. For many infertile women, childlessness is the most upsetting experience of their lives, and the yearning for children dominates everything. Infertility is stigmatizing, especially in some cultures. Infertile couples often suffer from self-reproach over sexual indis-cretions, abortions, or contraception. They envy fertile couples, and contacts with other people’s children, family celebrations, and friends’ pregnancies are problematic. The security of the marriage may be threatened by the fear that the spouse will desert to a fertile partner; nevertheless, the marriages themselves are often happy.
Infertility differs from other stresses in its duration. The psycho-
logical reaction unfolds over years. When treatment begins, there is 
a cycle of optimism and hope, with a build-up of tension towards 
the end of the cycle, followed by disappointment and despair.

the end of the cycle, followed by disappointment and despair. 
Sexual functioning comes under strain during the investigation, 
and the discovery of azoospermia is especially stressful. There is 
some evidence that stress affects conception, though more prospec-tive studies are needed.
Assisted reproduction
Artiﬁ  cial insemination (using the husband’s or partner’s semen) 
has been available from the late eighteenth century, and donor insemination since 1884. Its psychological effects on marriage seem minimal; husbands or partners rarely react with jealousy to the 5.4
Obstetric and gynaecological 
conditions associated with psychiatric disorder

1115
baby, any more than to an adopted child. The proof that the experi-
ence is acceptable is that it is often repeated. One of the principles is privacy, ensuring that donor and couple never meet and remain ignorant of each other’s identity. It is felt that violating anonymity might compromise the marriage, since donor and mother are too deeply involved in procreation to regard their relationship with detachment; but times may be changing. The interests of the chil-dren have to be considered; donor insemination obscures the genetic lineage, and the child cannot beneﬁ  t from advances in 
genetics.
In vitro  fertilization (IVF) was ﬁ  rst performed in 1978, and was

genetics.
In vitro  fertilization (IVF) was ﬁ  rst performed in 1978, and was 
achieved with a donated oocyte in 1984; it is now widely used—in Holland, 1/60 babies are born by IVF. The procedure is harrowing, and counselling is mandatory. There is an increase in multiple births, which are more stressful. But the quality of parenting may be superior to that of families with naturally conceived children.
Surrogate motherhood
This has two meanings:
◆ A woman is inseminated (artiﬁ  cially or naturally) with the hus-
band’s or partner’s semen, and surrenders the child to the genet-ic father and adoptive mother. The surrogate provides oocyte and womb, and is a substitute spouse.
◆ The wife donates a fertilized oocyte to the surrogate gestational 
mother. This method, involving in vitro  fertilization and embryo 
transfer, is the only way a woman without a uterus can have a child that is genetically her own.
A considerable number of women apply to become surrogate

A considerable number of women apply to become surrogate 
mothers, for motives of ﬁ  nancial gain, altruism, pleasure in being 
pregnant, or atonement.
(8) A child can now have 3 mothers—
genetic, gestational, and rearing.
Surrogate pregnancy has stirred up an ethical debate. Apart from 
religious objections, there is concern about the physical and psy-chological consequences for the gestational mother, and there are endless opportunities for custody disputes and other legal compli-cations. It has been found that the gestational mother does not bond strongly to the foetus, and most surrogate and commission-ing mothers do not suffer from psychological problems.
Pseudocyesis
When a woman believes herself to be pregnant and develops symptoms and signs of pregnancy, this is called pseudocyesis. In a classic monograph, Bivin and Klinger
(9) collected 444 cases

(9) collected 444 cases 
from the literature. Many sufferers were parous, including women with as many as 10 children, and as many as six episodes of pseudocyesis.
The differential diagnosis includes delusions of pregnancy, in 
which there are no somatic changes. This is a common delusion and can also occur in men. There is also pregnancy simulated for social, mercenary, or legal purposes (e.g. to escape the death penalty).
The clinical features include:
◆ a ﬁ rm belief in the pregnancy, usually lasting until the onset of a 
false labour at 9 months, after which the disorder usually resolves
◆ amenorrhoea
◆ morning sickness and/or pica◆ enlargement of the breasts and nipples, and even a discharge of 
colostrum
◆ abdominal enlargement, caused by muscular contraction,

colostrum
◆ abdominal enlargement, caused by muscular contraction, 
tympanites, fat, or pathological lesions, but without effacement of the navel
◆ an illusion of foetal movements
◆ enlargement of the uterus to the size of a 6-week pregnancy.
Modern diagnostic tests have greatly reduced the frequency. 
The diagnosis should be made on ultrasound examination. Where radiology or ultrasound are unavailable, an examination under anaesthetic is recommended—in the presence of a family member to avoid accusations of abortion.
The psychological basis is usually an intense desire for children, 
especially in older childless women. In some cases, however, a guilty fear of pregnancy has been the background; this has occasionally led to dangerous attempts at abortion by non-pregnant women. Pseudocyesis is a demonstration of the inﬂ  uence of psyche over

soma, mediated by hormonal secretion. It occurs in dogs, cattle, and rodents. Persistence of the corpus luteum would explain breast changes, moderate uterine enlargement, and secretory endometrium; but it is not the only basis: hormonal measurements have been made in at least 30 patients, some of whom had chronic anovula-tory states, hyperprolactinaemia, or androgen excess.
These women require psychotherapy. Simply revealing the diag-
nosis is unsatisfactory because the patient may consult another 
doctor with the same symptoms, or develop a recurrence. The 
underlying conﬂ  icts must be explored, helping the patient to accept 
that she is not pregnant.
Sterilization

Women can be prevented from bearing children by various operations on the uterus and Fallopian tubes, indications for which are contraceptive, medical, eugenic, or psychiatric. Sterilization is the most effective and widespread contraceptive method. A large number of studies have looked at its effect on mental health, but many had methodological weaknesses. Ekblad, however, published two thorough studies in 1950s—a general study of 225 women, of whom 99 per cent were interviewed 5 to 6 years later, and a unique study of 60 sterilized women with no living children.
(10)
There have been two modern prospective studies. Cooper and 
colleagues in Oxford(11) interviewed 201 women 4 weeks before

(10)
colleagues in Oxford(11) interviewed 201 women 4 weeks before 
non-puerperal tubal sterilization for contraceptive reasons; 190 were re-interviewed 6 months later, and 193 at 18 months after sterilization: the number with psychiatric illness fell from 21 before the operation to 9 at 6 months, and rose to 18 at 18 months. Not surprisingly, the presence of psychiatric disorder before the opera-tion was a predictor of its continued presence; only two who were in good psychological health before the operation developed psy-chiatric illness 6 months later. A WHO collaborative study, involv-ing ﬁ  ve countries (India, Colombia, Nigeria, Philippines, and 
England), compared 926 sterilized women with 924 who used other methods of contraception: those who chose sterilization had more preoperative psychiatric disorder. The results from the Nottingham ﬁ eld centre
(12) were published separately, and found that 9/138

(12) were published separately, and found that 9/138 
sterilized women had psychiatric disorder before the operation; 
after surgery there were only three new cases at 6 weeks, and four more at 6 months, less than the control group.5.4 obstetric and gynaecological conditions associated with psychiatric disorder

SECTION 5  psychiatry and medicine 1116
A small minority of sterilized women are troubled by frigidity or 
severe regret. The most concrete evidence is a request for reversal, several studies of which have been published. Regret is more com-mon in the following groups of women:
◆ Y ounger women or those with fewer children: Ekblad(10) found 
that none of his 60 childless women required hospitalization for depression, but 16 were seriously distressed and 29 expressed a longing for children of their own.
◆ Those in whom sterilization was the condition for a termina-
tion—a barbaric and punitive practice that used to be the rule in some countries.
◆ Those sterilized at a time of crisis—after parturition, or during 
a psychiatric illness—when it is difﬁ  cult to make a balanced 
judgement.
◆ Those under external pressure.
◆ Those with learning difﬁ  culties: the issue of sterilization, which

◆ Those with learning difﬁ  culties: the issue of sterilization, which 
has from time to time been practised in various countries, is becoming more important. With a policy of community care and a greater tolerance of sexual activity, there is an increased risk of pregnancy in women with severe learning difﬁ  culties, 
with the spectre of inherited disorders and problems in mother-ing. Y et these women greatly desire children, and do not have the same resources to compensate for their lack.
◆ Those sterilized for medical reasons such as inherited disorders, 
for which medical advances have later provided alternative solutions (e.g. amniocentesis).
◆ Those who seek sterilization in a context of marital disharmony: 
after the marriage has failed, the wife may remarry and change her mind about further children.
◆ Those with religious scruples.
Hysterectomy

This is one of the commonest operations, and is performed in about 10 per cent of women. There have been claims that it leads to ‘post-hysterectomy depression’ . But this idea has been thoroughly and systematically refuted. Several prospective investigations have shown that mental health improves after hysterectomy. Three com-parable Oxford studies, conducted between 1975 and 1990, have addressed this problem: all showed that psychiatric morbidity fell below its preoperative level, or remained low.
(13) The ranks of 
women with ‘post-hysterectomy’ depression are swollen by those seeking a surgical remedy for psychosomatic complaints.
In younger women, infertility can be a source of discontent. It

In younger women, infertility can be a source of discontent. It 
would not be surprising if the loss of the womb affected feminine identity and libido; but this is probably also a myth. Prospective studies from Oxford,
(13) St Louis,(14) and Aberdeen showed an 
increase in the frequency of intercourse, and of enjoyment. Concomitant oöphorectomy does not adversely affect psychiatric well-being.
(15)
The psychiatry of pregnancy
Pregnancy adjustment
The psychopathology of pregnancy needs to be understood in terms of the adjustment all women must make when they conceive. Pregnancy is not only a biological event, but also an adaptive 
process.
(16) A pregnant woman must carry the baby safely through 
to delivery, and adjust to the sacriﬁ  ces that motherhood demands.

process.
to delivery, and adjust to the sacriﬁ  ces that motherhood demands. 
She must ensure the acceptance of the child by the family, develop an attachment to the baby within, and prepare for the birth. She must adjust to the alteration in her physical appearance, and develop a somewhat different relationship with the child’s father.
Many pregnancies are unplanned and not initially welcomed. 
Many women react to conception with grief and anger. A random sample of English mothers showed that 44 per cent of pregnancies were unintentional, including 17 per cent that ended by legal abor-tion. In married women aged 25 to 29 years with one child, 80 to 84 per cent of pregnancies were planned, compared with 26 per cent in the unmarried.
(17) The planning of pregnancy and its acceptance

(17) The planning of pregnancy and its acceptance 
are two different things. The fact of planning does not guarantee acceptance; 6 to 12 per cent of those who plan their pregnancies subsequently regret them. Most unplanned pregnancies are imme-diately accepted; even if the initial response is negative, gradual acceptance usually follows. In a small proportion of cases, rejection continues to the end of the pregnancy.
Pregnancy has a profound effect on the relationship with the 
child’s father. At every stage this relationship is of the highest importance. A pregnant woman needs increased attention and care and is sensitive to perceived rejection. Pregnancy alters other rela-tionships as well—with the wider family and friends. Many women become closer to their families-of-origin and in-laws.
The change in appearance and shape is sometimes distressing. 
Some take pride and pleasure in these changes, enjoy the extra

Some take pride and pleasure in these changes, enjoy the extra 
attention, and feel an enhanced sense of womanliness. Others are concerned about their loss of ﬁ  gure and facial bloom, weight gain, 
and stretch marks. Dysmorphophobia, with ideas of reference and social avoidance can ensue.
Pregnancy may be accompanied by medical disorders, and in all 
there is an interaction between physical and psychological factors. Pica is common, especially geophagia (eating earth or clay), which can lead to iron deﬁ  ciency anaemia, bowel obstruction, and round-
worm infection; other forms of pica can lead to lead poisoning or hypokalaemia. Rarely, hyperemesis can cause Wernicke’s encepha-lopathy, and delirium can complicate chorea gravidarum.
(18)
Denial of pregnancy

(18)
In women who do not realize they are pregnant, one must distin-guish between three different phenomena: unnoticed pregnancy, deliberate concealment, and dissociative denial. A German survey of 29 000 births found 62 women who failed to recognize pregnancy until the 20th week (1/475 births); 12 were not diagnosed until they were in labour with a viable infant (1/2455).
(19) A Welsh study 
obtained similar ﬁ  gures.(20)
The late discovery of an unwelcome pregnancy carries a small 
risk of suicide. The mother is also at risk of all those complications of delivery that, with modern antenatal care, have become rare. For the child there are increased hazards, including prematurity and neonaticide.
Prenatal attachment
The mother ‘bonds’ or ‘afﬁ  liates’ to the unborn child in a way anal-

ogous to the formation of the mother–infant relationship after birth. Prepartum bonding is catalysed by quickening and probably by ultrasound examination. The mother begins to have fantasies

1117
about the baby and talks affectionately to it. She may engage the 
husband or partner and other children in ‘playing’ with the baby. At the same time she prepares for the birth and motherhood (‘nesting behaviour’).
There is a pathology of the afﬁ  liative stage. In some mothers 
there is minimal attachment even at term. The foetus is viewed as an intrusion, whose movements annoy the mother and disturb her sleep. A poor mother–foetus relationship is one of the predictors of impaired mother–infant bonding. When the mother’s attitude to the pregnancy is obstinately rejecting, therapists can direct her attention to the relationship with the child within. Stroking the abdomen and identifying foetal body parts, or telling stories about the baby’s future life, have been suggested.
Foetal abuse

When a mother deeply resents her pregnancy, she may try to harm the foetus. This occurs, with determined intent, in self-induced abortion. It may also occur as a manifestation of rage against the baby;
(21) a pregnant woman may pound on her abdomen, even to 
the point of causing bruising.
It is not only the mother who may ‘batter’ the foetus. Domestic 
violence is common and may increase during pregnancy, when kicks and blows are directed at the abdomen, rather than the face. The main factors are sexual frustration, substance abuse, jealousy, the mother’s irritability, and unreadiness for fatherhood.
The foetus is cushioned from external violence by the amniotic 
ﬂ uid, but can still be damaged by severe abdominal or pelvic inju-

ries. Domestic violence can lead to miscarriage, foetal death, and premature birth. Infants can be damaged by penetrating wounds, and there are over 100 instances of gunshot wounds to the gravid uterus—the result of murderous assaults, attempts to induce a late abortion, or suicide attempts.
Mental illness during pregnancy
(a) Anxiety
For many mothers, pregnancy is a time of considerable anxiety. The ﬁ rst trimester may involve an anguished decision whether to con-
tinue or terminate the pregnancy. Those who have previously suf-fered from prolonged infertility, multiple miscarriages or foetal loss are especially prone to prepartum anxiety. In the third trimester anx-iety is centred on three main themes: fears of parturition (tocopho-bia), of foetal abnormality, and of failure to cope with motherhood.

These anxieties will usually be managed by ventilation and support, 
but anxiolytic medication can be used cautiously. Of the anxiolytic agents, phenothiazines are relatively safe. Benzodiazepines are contraindicated in the last stages of pregnancy because of foetal intoxication (‘the ﬂ  oppy infant syndrome’). Propranolol is best 
avoided, because of reports of intrauterine growth retardation, and neonatal cardiac and respiratory symptoms.
Although prepartum depression has not aroused the same interest as postpartum depression, it is no less common. Depression is common in all women in the reproductive age group, and preg-nancy is not protective. Depression can be recurrent, and there is an association with puerperal mania.
The frequency of suicide is a vexed question. There are problems

The frequency of suicide is a vexed question. There are problems 
about the accuracy of the data since not all suicides are reported to the coroner, not all have necropsies, and not all necropsies include an examination of the uterus. In addition, both suicide and preg-
nancy are often concealed. One must therefore treat with scepti-cism those enquiries which do not scrutinize the primary records. Nevertheless, there is evidence that the suicide rate has declined throughout this century; in the ﬁ  rst quarter, about 13 per cent of 
women who committed suicide were pregnant—a rather high ﬁ  gure, 
suggesting that pregnancy was a risk factor at a time when illegiti-mate pregnancy was stigmatized. This was conﬁ  rmed by the thor-
ough mid-twentieth century study of Weir.
(22) More recent studies 
show rates below those in the general population.
Severe prepartum depression is sometimes left untreated, because

Severe prepartum depression is sometimes left untreated, because 
of fears about the effect of drugs on the foetus. These fears have been exaggerated. No antidepressive drug is known to have terato-genic effects. Most have no effect on the foetus, though ﬂ  uoxetine 
may reduce uterine blood ﬂ  ow and paroxetine may cause neonatal 
pulmonary hypertension. There are reports of toxic effects or with-drawal symptoms in neonates, so that medication is more to be avoided during the last trimester. Electroconvulsive therapy is safe, provided that the mother is competently oxygenated during anaes-thesia; pregnant women should be screened for rare syndromes of pseudocholinesterase deﬁ  ciency before receiving this treatment.
(c) Alcoholism
Pregnancy has a beneﬁ  cial effect on alcohol addiction, but, if heavy

Pregnancy has a beneﬁ  cial effect on alcohol addiction, but, if heavy 
abuse continues, there are severe effects on the foetus. The main effect is retardation of intrauterine growth
(23); although ethanol 
shortens gestation, the low birth weight is not explained by prema-turity, rather the infants are small for gestational age. The infant becomes addicted and may suffer neonatal withdrawal symptoms. Ethanol is also teratogenic, causing ‘the foetal alcohol syndrome’ (or ‘spectrum disorder’), ﬁ  rst described in France in 1968.
(24) The 
features include facial dysmorphism due to maxillary hypoplasia, and brain damage, resulting in long-term cognitive impairment and behavioural disorders (see also Chapters 9.2.7 and 10.4). In the detection of these severe complications, systematic prenatal screen-ing for alcohol abuse is useful.
(d) Other addictions
Cannabis  is commonly abused by pregnant women; it affects foetal

Cannabis  is commonly abused by pregnant women; it affects foetal 
growth, and may lead to long-term neurobehavioural and cogni-tive deﬁ  cits. Lysergic acid diethylamide  may have teratogenic or 
mutagenic effects. Phencyclidine  addiction leads to withdrawal 
symptoms.
Narcotic addicts , like alcoholics, have multiple emotional and 
social problems, and many do not seek antenatal care. The infants may be affected by maternal malnutrition and infections such as venereal disease, hepatitis, endocarditis, and AIDS. Narcotics are not teratogenic, but a high proportion of the infants are of low birth weight, partly explained by prematurity, and partly by intra-uterine growth retardation. A withdrawal syndrome develops in most babies. The perinatal mortality rate and frequency of sudden infant death, are increased. There is an increased incidence of 
microcephaly, and there may be impaired mental development,

microcephaly, and there may be impaired mental development, 
although other factors in the maternal life style may account for this. Methadone maintenance reduces the effect on birth weight; but it may depress respiration in the newborn, and lead to a more severe and prolonged withdrawal syndrome, with a greater fre-quency of seizures. Buprenorphine may be a more suitable mainte-nance therapy, with milder withdrawal effects. If it is decided to withdraw heroin, this should be done in the second trimester, 5.4 obstetric and gynaecological conditions associated with psychiatric disorder

SECTION 5  psychiatry and medicine 1118
replacing it by methadone. Naloxone, which can be given by 
implant, has been used, although there are concerns about foetal abstinence syndromes. After birth, the infants should be kept in hospital for at least 14 days. Respiratory depression can be treated by naloxone, and seizures and withdrawal symptoms by sedatives such as diazepam, or by tincture of opium.
Cocaine  may be teratogenic, causing genitourinary and cardiac 
abnormalities, but the evidence is conﬂ  icting. Its main effects are

abnormalities, but the evidence is conﬂ  icting. Its main effects are 
cardiovascular: it causes uterine vasoconstriction, and this can lead to placental abruption. The infants may suffer cerebral infarction. There is intrauterine growth reduction and an increased incidence of microcephaly. Premature labour is common. There is a with-drawal syndrome, but this is less severe than with narcotics. There is some evidence of an increased risk of sudden infant death. Long-term effects on language development and behaviour are contro-versial, and may be due to confounding factors such as maternal depression, other drugs, and the environment.
All these mothers should receive close psychiatric supervision 
and social casework. Hair and meconium analysis improves the diagnosis of opiate and cocaine abuse in mothers who present unexpectedly in labour.
(e) Eating disorders

There are psychological and somatic reasons for an antagonism between pregnancy and anorexia nervosa; nonetheless, most anorexic women recover, and menstruate when their weight reaches about 80 per cent of the standard weight. Ovulation can be induced by clomiphene or menopausal gonadotrophin in those who fail to menstruate. There are numerous case reports and several long-term studies showing that many women with a history of anorexia nervosa give birth to children in the normal way. The overall effect on fertility has been quantiﬁ  ed by a 12-year Danish 
study; the average number of children (0.6) was about one-third the usual ﬁ  gure.
(25) The desire for children is shown by the freque ncy 
of infertility treatment, planned pregnancy, and breast feeding.
A minority become pregnant while in the throes of the disease.

A minority become pregnant while in the throes of the disease. 
Anorexic amenorrhoea may delay the diagnosis. Pregnancy usually has a beneﬁ  cial effect; but if the mother continues to restrict her 
diet, the foetus may suffer from malnutrition. Occasionally it has been necessary to rescue the infant by elective Caesarean section. There is a tendency to relapse in the puerperium. When mothers are actively anorexic, there is often conﬂ  ict at mealtimes; occasionally 
children may become involved in their mother’s asceticism, and suffer stunted growth.
Bulimia nervosa is often improved by pregnancy. The pressure of 
the enlarging uterus on the stomach makes bingeing more difﬁ  cult. 
About half relapse after delivery.
(26) Pregnancy is not much affected

(26) Pregnancy is not much affected 
by bulimia, but low birth weight has been reported. Bulimic moth-ers sometimes show deviant mothering, ignoring or excluding their children while overeating or vomiting, or restricting food supplies.
(f) Obstetric factitious disorder
Self-induced illness behaviour can extend into the obstetric domain.
(27) Women may induce bleeding to simulate threatened 
miscarriage, placenta praevia, or postpartum haemorrhage. They may stimulate rupture of the membranes to precipitate an early delivery. Others have been caught manipulating instruments, for example an external tachodynamometer. Two patients even attempted to simulate hydatidiform mole, by adding human chori-onic gonadotrophin to blood samples.(g) Psychosis
Numerous asylum surveys have testiﬁ  ed to the lower frequency of 
psychosis during pregnancy than after delivery. This was conﬁ  rmed

psychosis during pregnancy than after delivery. This was conﬁ  rmed 
by Kendell and colleagues, in their linkage of Edinburgh obstetric and psychiatric case registers
(28): in a study of 54  087 births, they 
found rates of 2.1 per month before conception and 2.0 per month during pregnancy, much lower than after childbirth (51 in the ﬁ  rst 
month).
Pregnancy probably has no effect on chronic delusional states, 
but it does have a beneﬁ  cial effect on menstrual, bipolar, and pos-
sibly cycloid (acute polymorphic) psychoses.
(29) Nonetheless, acute 
manic and cycloid episodes occur during pregnancy, and some seem remarkably similar to puerperal psychosis. They would be regarded as sporadic or random, except that they have been observed in women with a history of puerperal psychosis (at least 13 in the literature).
(30) There is an association with multiparity, 
with the postpartum episode occurring ﬁ  rst.

Neuroleptic agents appear to be safe during pregnancy. 
Phenothiazines and butyrophenones are not teratogenic. The main (but infrequent) hazard is sedation and extrapyramidal symptoms in the newborn. Lithium is relatively dangerous; at least 12 cases of the rare Ebstein’s anomaly have been reported. As delivery approaches, reduced renal clearance can result in toxicity with nor-mal doses; eight cases of alarming blood levels (up to 5 mmol/l) have been reported, with coma and convulsions in the mother. Even at normal blood levels, babies exposed to lithium have suffered lethargy, hypotonicity, and other effects. Carbamazepine has been associated with rather high rates of congenital abnormal-ity, and sodium valproate is particularly dangerous, with major 
abnormalities especially spina bifida, and a foetal valproate syndrome.
(h) Obstetric liaison services

In view of the complexity of the psychological response to preg nancy, 
and the frequency of anxiety, depression, and other psychiatric disorders, there should be good liaison between obstetric and psychiatric services. In addition to the need to diagnose and treat prepartum psychiatric disorders, the high level of supervision in the antenatal clinics offers an opportunity for preventive psychiatry, by screening for vulnerable women, including those with unwanted pregnancies, severe social problems, or a history of psychosis, addictions, or depression.
The psychopathology of parturition
Childbirth can be one of the severest of human ordeals, and in spite of its brevity, is a time of risk for psychopathology.
(18) In advanced

(18) In advanced 
countries, all these complications are rare, but may still be com-mon where obstetrics is primitive, or pregnancy denied. Acts of desperation, such as auto-Caesarean section or suicide, and rage attacks, endangering the foetus, are fully described in the older lit-erature. Delirium is well documented; in most cases, it lasts a few hours, starting shortly before delivery and disappearing after the birth, with amnesia for the event; but it can continue into the puer-perium, or start immediately after the birth. Engelhard
(31) gave 
the best estimate of its frequency: in a 10-year survey, there were ﬁ ve cases of transitory confusional states in 19 910 births. The exis-
tence of this phenomenon aggravates the jurisprudential problem of neonaticide, because, in an unattended delivery, it is impossible

1119
to know whether or not the mother was temporarily confused. 
Unexplained stupor or coma has also been described during and immediately after delivery.
Infant loss
The child may be lost for a variety of reasons:
◆ termination of pregnancy at the behest of the mother
◆ miscarriage, ectopic pregnancy, and late termination of a wanted 
child for medical reasons
◆ foetal death in utero , stillbirth, neonatal death, and sudden infant 
death (‘cot death’ , SIDS)
◆ relinquishment to adoption.
(a) Termination of pregnancy
The indications for abortion include the following:
◆ medical—to preserve the health and life of the mother
◆ humanitarian—when pregnancy has resulted from rape or incest
◆ eugenic—where there is a risk of congenital abnormality
◆ psychiatric
◆ social—because pregnancy is untimely and disruptive
◆ on demand—in the belief that women should be free to decide 
when to have children.
There has been a debate on the validity of the psychiatric indica-

tions; this turns on the psychiatric consequences of a refusal to terminate. Suicide threats are common, but are rarely carried out; nevertheless there can be no doubt that unwanted pregnancy is a factor in completed suicide. A history of puerperal psychosis is not an indication, because it is equally likely to follow abortion; but there are other, arguably more serious, puerperal complications such as mother–infant relationship disorders, which are more com-mon and severe after unwanted pregnancy. These can be avoided by adoption, but the psychological effects of relinquishment are not negligible.
The psychological effects of termination have been thoroughly

The psychological effects of termination have been thoroughly 
explored. Most who voluntarily abort suffer no adverse effects, either in the short or long-term. There is often relief, even euphoria, and a reduction in anxiety, depression, anger, guilt, and shame. A minority experience regret and self-reproach over the ‘murder’ of the baby. Some feel like criminals and worry about punishment, a 
nemesis of sterility or future congenital malformations. A few develop clinical depression. A Finnish study showed that the suicide rate 
was increased from 11/10
5 to 35/105.(32)
There is a literature on ‘postabortion psychosis’ , but both parts of

There is a literature on ‘postabortion psychosis’ , but both parts of 
the term have multiple meanings; ‘abortion’ refers to miscarriage, termination, criminal abortion, and even stillbirth after short gesta-tion, and ‘psychosis’ includes delirium, Wernicke–Korsakow syn-drome, melancholia, and psychogenic paranoid disorders. Manic or cycloid episodes, similar to puerperal psychosis, occur after abortion: apart from epidemiological evidence
(33) and individual cases, the 
association of postabortion and postpartum psychosis in the same woman has been reported on at least 14 occasions.
(30) Some episodes 
occurred after miscarriage, but several followed termination, in most cases performed to prevent a recurrence of puerperal psychosis.
T o minimize the psychological risk, prudent decision taking is of 
the essence, and counselling has a valuable role. The most difﬁ  cult part of the experience is the loneliness and isolation. Many do not

the essence, and counselling has a valuable role. The most difﬁ  cult part of the experience is the loneliness and isolation. Many do not 
inform their parents, and, when they do, face censure and unwel-come pressure. The attitude of the child’s father is crucial. Attempts should be made to involve him in all aspects of the experience; unfortunately his reaction is often unhelpful. It is axiomatic that a woman should make her own decision—one of the most difﬁ  cult 
she will ever take. It often has to be taken hastily, in an atmosphere of conﬂ  ict and turmoil. The best outcomes are found when a 
woman makes her decision in a context of respect and support from partner, parents, friends, or counsellor.
(b) Miscarriage

This is a common event, perhaps 40 per cent of all conceptions, but only 10 per cent occur after pregnancy is recognized by amenor-rhoea or other signs. An ectopic pregnancy is gynaecologically more serious, but has the same psychological effects. The emotional consequences of miscarriage are not trivial, and can be compared to perinatal death—less severe, because there has been little time for attachment to the newly conceived, but still the loss of a greatly desired child. The event itself, with foetal tissue passed suddenly and painfully, may be disturbing. Some of the psychological symp-toms may resemble post-traumatic stress disorder, with intrusive re-experiencing (‘ﬂ  ashbacks’) and nightmares. There is a sense of

failure, guilt, and anger. The incidence of depression is four times the rate found in the general population. There may be depressive episodes at the time of the expected delivery, anniversary reactions, 
and an increased risk of postpartum emotional disorder after a 
later normal delivery.
Helping a mother who has suffered a miscarriage is a variant of 
grief therapy, in which her intense distress is shared, and sadness, guilt, and anger ventilated.
Late termination for medical reasons, although a deliberate 
intervention, is psychologically similar to miscarriage and to foetal death in utero . Some wish to continue the pregnancy in the full 
knowledge that the baby will be abnormal. Depression is common, and grief long-lasting. All these women require counselling, before and after the termination.
(c)  Foetal death in utero , stillbirth, neonatal death, and 
sudden infant death
Reactions to these events are generally more severe than to miscar-

riage, and each has its special characteristics. When the baby dies in late pregnancy, the mother carries a corpse within her, and must undergo a futile labour. If it dies during labour, the loss is sudden and shock pronounced, with a strong sense of unreality. When the child dies in the ﬁ  rst week, the parents have to endure great anxiety, 
with dwindling hope; they may be involved in the decision to switch off the respirator, and witness the child dying. The later death of an infant, when the maternal emotional response is fully developed, especially sudden infant death, is at the very top of the catalogue of calamities; there is no warning or preparation, and the death is followed by a forensic investigation.
(d) Grief after infant loss

This is similar to other grieving, but has its own special character. There is shock, followed by emotional numbness and emptiness, then long-lasting and agonizing sadness. Grief hallucinations (of foetal movements, the baby’s face, the infant crying or playing in the cot) may be experienced. There is guilt, anger, and recrimina-tion. There are various crises, especially the disposal of toys, baby 5.4 obstetric and gynaecological conditions associated with psychiatric disorder

SECTION 5  psychiatry and medicine 1120
clothes, and nursery furniture, as well as meeting friends and rela-
tives; some, ﬂ  oundering in their embarrassment, are evasive and 
unable to comfort or sympathize (‘wall of silence’). Especially after SIDS, there may be shame, stigma, and even ostracism or malicious speculation. Envy of successful mothers is a problem; there may even be a temptation to steal babies. Surviving children may be confused by their parents’ grief, upset by family turmoil, and deprived of attention and care; they are also grieving and preoccu-pied with their own search for the meaning of death.
(34)
When helping the parents,(35) the principles are as follows:
◆Honesty and openness in communication . The admission of

(34)
◆Honesty and openness in communication . The admission of 
errors is delicate, but the parents’ guilt should not be reinforced by the obstetric team’s refusal to accept responsibility. Recrimination, litigation, or querulant reactions are common. Staff should accept this as normal, and try not to be defensive. After a stillbirth, most mothers prefer to be segregated, and discharged early. One or more interviews with the consultant obstetrician are indicated. It is essential that the mother is visited by a member of the primary care team. A lactating mother may need bromocriptine, or to donate milk to a milk bank. Hypnotics may help mothers troubled by insomnia. The doctor should be alert for secondary depression.
◆All parents want to know why the baby died . The necropsy can

◆All parents want to know why the baby died . The necropsy can 
help, but parents should be warned that often no explanation is found. Necropsies in SIDS are specialized; the pathologist can play a vital psychological role, and should be available for discussion.
◆Mementoes  should be kept, including a photograph. The dignity 
of naming and a burial ceremony is helpful. The value of seeing and holding the dead baby has been challenged.
(36)
◆The bereaved mother needs to share her distress . A sensitive 
and sympathetic person, with the time and interest to listen, can help her grieve and accept her loss. This support will often come from the husband or partner, family, or friends. If not, pro-fessionals, especially chaplains or nurses, should step in. Self-help groups and voluntary agencies are invaluable for some mothers.
◆The next pregnancy . No doctrinaire advice can be given

◆The next pregnancy . No doctrinaire advice can be given 
about the timing of the next pregnancy. Increased anxiety during pregnancy and the puerperium can be expected.
◆The grieving sibling . The routine and rhythm of family life 
should be disturbed as little as possible. The parents should not be afraid to show their emotions—it is best to acknowledge their sadness, and how much they will miss the baby. They should try to give a factual account of what happened, avoiding euphe-misms. It is important to reassure the children: they are not responsible and will not lose the love of the parents; neither they nor their parents are in imminent danger of death. The child can be helped to grieve by looking at pictures of the dead sibling, attending the funeral, and visiting the graveyard. (see Chapter 9.3.7 for further information about bereavement in childhood.)
(e) Relinquishment
Adoption used to be the main way to satisfy the longing to rear

Adoption used to be the main way to satisfy the longing to rear 
children and to handle accidental pregnancy, but there has been 
a great social change in Europe and North America. Since 1950, 
the number of children born to single mothers has climbed steeply, and is still climbing, but, despite this increase, the number of adoptions is falling steadily. This is not due to spectacular 
improvements in the infertility treatment, reducing the demand, nor to the relaxation in the abortion laws, reducing the supply, but a new tolerance of single motherhood. In partial compensation for the scarcity of relinquished babies, the practice of adopting foreign-
born children has arisen.
Although adoption is on the wane, attention has been focused 
on the psychological effects of relinquishment.
(37) For some relin-
quishing mothers, giving up the child is a painful, loving act of selﬂ ess courage. In others it is the enforced loss of a living child,

quishing mothers, giving up the child is a painful, loving act of selﬂ ess courage. In others it is the enforced loss of a living child, 
with a charade of informed consent. Relinquishment is among the most stressful of events. Instead of understanding and support, there is often loneliness and ostracism. Time is no healer; the child continues to exist and can be seen again, and there is often a fantasy of reunion or restitution. As time goes on, there is a new compo-nent; the adult child may seek its biological mother, and there is the hope that this event, which she cannot inﬂ  uence, may happen. 
There has been a growth in the number of organizations to help relinquishing parents ﬁ  nd their offspring. Many countries are 
grappling with the problems of legislating for reunions.
T o avoid these severe and prolonged psychological effects, a 
relinquishing mother needs counselling during the pregnancy. The

relinquishing mother needs counselling during the pregnancy. The 
aim is to emerge from the experience with self-respect and dignity. After delivery the mother should be encouraged to see the infant and photographs should be ﬁ  led. Follow-up counselling should be

aim is to emerge from the experience with self-respect and dignity. After delivery the mother should be encouraged to see the infant and photographs should be ﬁ  led. Follow-up counselling should be 
continued for at least 6 months. The mother may wish to join a society for relinquishing parents. There is also the relationship with the adopting family to consider. Adoptive parents should accept any gift or token of the natural mother’s love. Information on the outcome of the child should be available. Some birth-mothers wish to provide up-to-date information, so that the child knows they are now respected citizens. A recent innovation is the practice of ‘open adoption’ , in which both sets of parents meet. There is even ‘continuing open adoption’ , which means that they remain in contact over the course of the child’s development.
The psychiatry of the postpartum period
The normal puerperium

For many or most mothers, giving birth is a supreme moment, and euphoria or elation is common. Some may be too excited to sleep. These feelings of peace, fulﬁ  lment, and accomplishment help to 
sustain mothers during the weeks of strain that follow. Prolonged euphoric reactions, lasting a week or more, are probably mild puer-peral mania, and are often followed by depression.
Newly delivered mothers have to face a number of challenges, 
including the following. 
◆Physical exhaustion . This can be coupled with the painful 
sequelae of pelvic trauma.
◆Breast feeding . Although this has many advantages, it is often 
difﬁ cult to establish.
◆Insomnia . Sleep deprivation, especially during the ﬁ  rst month, 
is a cause of irritability, and should be borne in mind when mothers present ‘at the end of their tether’ .
◆Recovery of normal ﬁ  gure and attractiveness . This may be

◆Recovery of normal ﬁ  gure and attractiveness . This may be 
threatened by weight gain and stretch marks. Mothers may occasionally develop a state similar to dysmorphophobia.
(38)

1121
◆Loss of libido . Episiotomy and vaginal trauma often cause 
dyspareunia; fatigue may depress sexual activity. Nevertheless sexual relations are usually resumed within 1 to 3 months, though reduced in frequency, and with a delayed return of orgasm. For this and other reasons (e.g. jealousy) the marriage may come under strain.
◆Social privation . The loss of employment, income, and leisure, 
as well as conﬁ  nement to the house, are all contributory factors.
With this background of rapid biological, social, and emotional 
transition, it is not surprising that a wide variety of psychiatric disorders occur; indeed the psychiatric complications of childbirth are more numerous and complex than in any other human situation.
The maternity ‘blues’  is so common as to be almost normal. 
Usually between the third and ﬁ  fth days, many mothers experience 
a sudden, ﬂ  eeting, and unexpected period of sensitivity and unchar-

acteristic weeping. In the great majority this passes off within a few hours, or a day or two. There is some evidence for an association between this brief dysphoric reaction and postpartum depression.
Reactions to severe labours
After excessively painful labours, some women suffer nightmares, and repetitive daytime intrusion of images and memories, similar to those that occur after the harrowing experiences of war and natural disaster. Since the original description,
(39) over 40 papers

(39) over 40 papers 
have been published on this subject, including 10 quantitative studies showing rates of up to 5.9 per cent of deliveries. Many of these women avoid further pregnancy (secondary tocophobia), and those who become pregnant again may experience a return of symptoms, especially in the last trimester.
This disorder can be treated by counselling and by speciﬁ  c 
psychological therapies. T ocophobia is an indication for elective Caesarean section.
(b) Querulant reactions
Another reaction to a severe labour experience is pathological complaining ( Querulantenwahn ). These women complain bitterly 
about perceived mismanagement, and their angry rumination may continue for weeks or months, interfering with infant care. Some conﬁ  ne themselves to vengeful fantasies and verbal or written criti-
cism, but others proceed to litigation. Careful assessment is needed to distinguish these reactions from reasonable complaining.

This disorder can be treated by a psychotherapeutic approach, 
which distracts the mother from her grievances and reinforces productive child-centred activity.
Postpartum anxiety disorders
Recent research has shown that postpartum anxiety disorders are just as common as postpartum depression.
(38, 40)  A review of eight 
studies of ‘panic disorder’ showed that 44 per cent of anxious women had an exacerbation, and 10 per cent a new onset, in the 
puerperium.
(41) It is important to identify the focus, as well as the 
form, of anxiety, because there are several themes that indicate spe-
ciﬁ c psychological therapies. Benzodiazepines should be used with

ciﬁ c psychological therapies. Benzodiazepines should be used with 
caution in lactating mothers. They are well absorbed from the gut, and more slowly metabolized in the neonatal liver, and occasionally cause lethargy and weight loss in breast-fed infants.(a) Puerperal panic, and phobic avoidance of the infant
Some mothers, especially primiparae  in isolated ‘nuclear’ families, 
are overwhelmed by the responsibility of caring for the newborn.(42)
The panic and agitation seen in extreme examples is an exaggera-tion of the anxiety that many women experience when they ﬁ  rst 
confront this awesome task. If no help is available, a mother can develop a phobic avoidance of the infant,
(43) and risks losing her 
mothering role.
These disorders can often be handled by the wider family, without

These disorders can often be handled by the wider family, without 
invoking professional help. The mother needs sedation, especially at night. During waking hours, she should remain with the baby, but must be supported at all times. Treatment is by desensitization. Gradually the mother takes over, at her own pace, undertaking the easiest tasks ﬁ  rst, and involved in all decisions. In severe cases, con-
joint admission may be the only way to rescue the situation. With correct diagnosis and management the prognosis is excellent.
(b) Anxieties about infant health and survival

The care of an infant involves ceaseless vigilance. In women prone to anxiety and excessive worrying, or in those who have suffered years of infertility or recurrent miscarriage, motherhood can lead to excessive solicitude about banal tasks that put the baby at risk (e.g. bathing) and sensitivity to the slightest indication of illness. In some, the anxiety is focused on the possibility of sudden infant death.
(44) These mothers lie awake listening to the baby’s breathing; 
sleep with their hand on the infant’s chest, check the infant many times each night, or even wake the baby to ensure that he or she is still alive. This results in excruciating tension, insomnia, and exhaustion.
These mothers require anxiety management. Day-hospital

These mothers require anxiety management. Day-hospital 
attendance, with relaxation therapy and group support is ideal. A mother with ‘fear of cot death syndrome’ may be helped by expla-nations about the rarity of SIDS, and the infant’s resistance to asphyxia, as well as devices to monitor the infant’s breathing. The vicious cycle of insomnia and hypervigilance can be interrupted periodically by involving relatives or friends, so that she can sleep under sedation. Ventilation, and the support of mothers who have recovered from similar problems, is helpful. However, these are 
only palliatives, because the underlying cause is an event, which, 
albeit uncommon, remains possible during a period of several months.
Puerperal obsessional disorders
There is evidence that the puerperium is one of the main pre-cipitants of obsessive–compulsive disorders.
(45,46)  In addition to

(45,46)  In addition to 
obsessional rituals, the disorder may present with thoughts, images, or impulses of child harm. These impulses to attack the child must be distinguished from the pathological anger that precedes child abuse. The mother is gentle and devoted. She experiences extra-vagant infanticidal images, such as stabbing, decapitation, or strangulation. She fears being left alone with her infant, and may 
take extraordinary precautions.
(47) The obsessional content may 
be of child sexual abuse, for instance masturbating or castrating their sons.
Ventilation, explanation, and psychotropic medication are part

Ventilation, explanation, and psychotropic medication are part 
of the treatment, but are rarely sufficient. It is important to discourage avoidance of the child, and encourage cuddling and play, thus strengthening positive maternal feelings. Cognitive–behavioural treatment can help her to achieve mastery over 5.4 obstetric and gynaecological conditions associated with psychiatric disorder

SECTION 5  psychiatry and medicine 1122
 irrational impulses. (For the treatment of obsessive–compulsive 
disorder, see Chapter 6.3.2.1.)
Puerperal melancholia was one of the ﬁ  rst postpartum psychiatric 
disorders to be identiﬁ  ed. During the asylum era, only the most 
severe cases were admitted, and the occurrence was underestimated when compared with ‘puerperal mania’ . When, in the 1950s, atten-tion turned to milder disorders, postpartum depression was found to be common in the general population. The pioneering work of the Gordons in New Jersey
(48) was soon widely conﬁ  rmed. In the 
last 10 years there has been a ﬂ  ood of papers from all over the 
world. Surveys have shown rates of at least 10–20 per cent, or even higher in the ‘Third-World’ .
(49) ‘Postnatal depression’ has become a

(49) ‘Postnatal depression’ has become a 
household word. It is an important lay concept, which has legiti-mized maternal depression in the minds of the public, providing a valid explanation for role failure, diminishing stigma, enabling mothers to accept that they are ill, and to come forward for treat-ment. It is a slogan that can be wielded in the political struggle to obtain better services for mothers of young families. There is a need for such concepts, which have social inﬂ  uence.
However, one must examine the scientiﬁ  c value of this concept 
with scepticism. Depression after childbirth is clinically similar to any other depression, and the association of depression with the puerperium is not striking. Whatever the prevalence in surveys, only about 5 per cent consult their general practitioners. The 
epidemiological evidence is weak. The suicide rate in the ﬁ  rst post-

partum year is below the female rate.
(32) Depression is common 
in women during the reproductive years, whether they are infertile, pregnant, puerperal, menopausal, or involved in child rearing. The term ‘postnatal depression’ has the danger of introducing into the minds of the unwary the mirage of a homogeneous disorder with a single cause. Rather, it is a rubric for a heterogeneous group of disorders. Many mothers with anxiety, obsessional, or post-traumatic disorders, or with a disturbed infant relationship, are depressed, but the setting, causes, and treatment are different. Not surpris-ingly, research into its causes has found that they are the same as those that cause depression at all ages—heredity, a history of previ-ous or prepartum depression, ‘neuroticism’ , adverse events or social conditions, difﬁ  cult relationships, and social isolation. It has been

suggested that the burden of child rearing, rather than child bear-
ing, is a factor, but this has been challenged by a Swedish twin 
study
(50) and a Norwegian suicide study(51) showing that parous 
women have a lower risk of depression than nulliparous women. In mothers with recurrent puerperal depression one would expect to ﬁ nd speciﬁ  c factors. Adjustment to motherhood has received much 
less emphasis than it deserves; unwanted pregnancy has been found to be a predictor of antepartum and postpartum depression.
Whatever its frequency, the effects of depression on family life, 
and the emotional climate in which children are reared, is of great concern. A growing child needs emotional support, attention, approbation, and stimulation. The mother is the child’s primary environment, and her mood dominates his or her world. Even very young infants are disturbed by deviant social behaviour in the mother. Although deﬁ  cits are not universal,
(52) her depression can

(52) her depression can 
lead to inattention through anergia or brooding, reduced quantity, quality, and variety of interaction, and loss of the reinforcement of the mother’s gaiety and tenderness. Her anger may be misdirected at the children. Frequent irritability, impatience, and criticism induce social withdrawal, anxiety, and reciprocal anger. There may 
be educational deﬁ  cits. These effects depend on the degree and 
duration of maternal depression, and the extent to which it involves interactions with the child. (See Chapter 9.3.6 for further informa-tion on the effects of maternal depression on child development.) In extreme cases, maternal depression can lead to the tragedy of combined suicide and ﬁ  licide.
Treatment begins with effective diagnosis. Many more mothers

Treatment begins with effective diagnosis. Many more mothers 
are depressed than ever make their way to the surgery. The reasons for the failure to seek help are not fully understood: some recover early, some do not realize they are ill, and some are ashamed of con-fessing their symptoms, suffering in silence because of ignorance, stigma, and fears of losing their baby. Screening procedures help the primary care services to identify cases; an example is the Edinburgh Postnatal Depression Scale,
(53) which has high sensitivity and speci-
ﬁ city. Patients identiﬁ  ed by screening, or self-referral, require a full 
psychiatric examination, in order to identify vulnerability factors and the speciﬁ  c components of postpartum disorders. This initial

psychiatric examination, in order to identify vulnerability factors and the speciﬁ  c components of postpartum disorders. This initial 
interview is best held at home, because clinic attendance is an obsta-cle for mothers fettered with the care of young children, and because domiciliary assessment has a quality that cannot be achieved in the ofﬁ ce. The interview should explore the symptoms and course of 
the illness, study its context in the mother’s life history, personality, and circumstances, review the events of this pregnancy, explore the mother’s relationships with her spouse, baby, other children, and family of origin, and establish the available supports.
Treatment is focused on depression and any underlying vulner-
ability. It will always involve psychotherapy, if only in the form of a single interview; it will usually include medication or other 
specific treatments; a few require electroconvulsive therapy.

specific treatments; a few require electroconvulsive therapy. 
Working with the baby’s father, potentially the main supporter, is important; fathers can come under strain, either because their wife’s intimacy with the baby disturbs conjugal dynamics, or because her depression has a domino effect on him. Home visits by community nurses are an ideal method of delivering continuing care and psychotherapy. An extensive literature has accumulated demonstrating the efﬁ  cacy of psychological treatments by double-

blind randomized controlled trials. As for drug treatment, there is no evidence that any drug is superior to others. There are at least 50 reviews of drug treatment in lactating mothers. The suckling infant has little body fat, less plasma protein-binding, an immature liver and kidney and an undeveloped blood-brain barrier. But the risks are minor. Only a minute dose is delivered to the infant: Epperson and colleagues demonstrated that serotonin re-uptake blocking agents do not affect serotonin levels in breast fed infants.
(54) Occasionally, babies have been over sedated. It is 
not recommended that antidepressant agents be withheld, or that breast-feeding be stopped; but it is wise to use these drugs cau-tiously, and it may be helpful to take the drug after breast feeding 
(see also Chapter 6.2.3).
Prevention is important in mothers with a history of severe or

Prevention is important in mothers with a history of severe or 
prolonged postpartum depression. They often present during the next pregnancy, requesting advice or prophylaxis. If they are already symptomatic, or have obvious risk factors such as marital friction or social isolation, they need support from community psychiatric nurses, voluntary agencies, or other groups. If they are well, it is only necessary to establish contact, so that a recurrence is diag-nosed and treated promptly. Prophylactic antidepressant medica-tion can be considered.

1123
Mother–infant relationship disorders
Just as the emerging relationship with the foetus is important dur-
ing pregnancy, so also the growth of the mother–infant relationship is the key psychological process in the puerperium. ‘Bonding’ is a popular lay term; some professionals prefer ‘attachment’ , but one must not confuse this with infant–mother attachment. The mother–infant relationship consists essentially of ideas and emotions aroused by the infant, which ﬁ  nd their expression in affectionate and protec-
tive behaviour. Its immense power is revealed in self- sacriﬁ  ce, and

tive behaviour. Its immense power is revealed in self- sacriﬁ  ce, and 
the pains of separation. Its inner presence is betrayed by external signs—touching and fondling, kissing, cuddling and comforting, prolonged gazing and smiling, baby talk and cooing, recognizing signals, tolerating demands, and resisting separation; but it is hard to select a single activity that lies at the core. Particular behaviours wax and wane, but the relationship endures, even when the child is absent, even when it is gone for ever. This emotional response enables the mother to maintain the never ending vigilance, and endure the exhausting toil of the nurture of the newborn.
There is no ‘critical period’ in the development of the maternal 
response. Close proximity from the start (‘rooming-in’) gives conﬁ  -

dence in mothering skills, and breast-feeding may help. The infant plays an important part. At an early stage, it can discriminate speech, and reacts preferentially to the human face and voice. Eye-to-eye contact mediates the interaction, and gazing becomes an absorbing activity on both sides. The baby’s smile is another catalyst. Videotape studies have shown the infant contributing to a dialogue with its caregiver. Sometimes the maternal response is immediate, primed by afﬁ  liation to the foetus, but sometimes there is a worrying delay. 
For the ﬁ  rst 3 to 4 weeks many mothers feel bruised, tired, and inse-
cure, and their babies seem strange and distanced. As the baby begins to respond socially, a normal relationship develops rapidly.
The term ‘mother–infant relationship (or bonding) dis orders’ cov-

ers a spectrum of clinical states, which has two main  dimensions:
◆ An absent or negative emotional response. In severe cases, the 
mother regrets the pregnancy and expresses dislike or hatred of her baby. She may try to persuade her own mother, or another relative to take over, and may demand that the infant be fostered or adopted. The most poignant manifestation is a secret wish that the baby ‘disappear’—be stolen, or die.
◆ Pathological anger. The infant’s demands anger the mother 
and provoke aggressive impulses, which may lead to shouting, cursing, screaming, or assaults.
There is at present little data on the frequency of these disorders

There is at present little data on the frequency of these disorders 
in the general community. At the level of ‘threatened rejection’—where the mother has an aversion to her child and seeks temporary escape from child care (the threshold for active intervention)— the frequency of these disorders in the general community is probably about 1 per cent. It is much higher in mothers who seek help for ‘postnatal depression’—about 10 per cent at the level of established rejection, and another 15 per cent for threatened rejection.
(55)
These disorders are usually accompanied by depression, but there 
are many reasons to reject the euphemism ‘postpartum depression with impaired mother–infant interaction’ .
◆ A disturbed relationship is different from a mood disorder.
◆ When depression is associated with phobias, obsessions, or devi-

ant behaviour, these co-morbid phenomena are still considered worthy of study and treatment in their own right.◆ Impaired interaction, although it can be recorded and measured, 
is not the essence of the phenomenon, but merely its behavioural manifestation; it has other causes, especially infant-centred anxiety.
◆ Aversion to the infant is not conﬁ  ned to depressed mothers;(56,57)
◆ When they coexist, their severity and course often differ.
◆ Only a minority of depressed mothers have this problem. It is 
important to select them for treatment and not to stigmatize the others.
◆ The risks—including child abuse and neglect—are higher. It is 
these disorders, rather than uncomplicated depression, that have serious and long-term effects on the child’s development.
(58)

(58)
These mothers are a high-risk group that can contribute to the vital task of preventing child abuse and neglect.
◆ The treatment is different and speciﬁ  c (see below). Assessment 
and treatment of this relationship forms an important part of 
the work of mother–infant mental health teams.
◆ Management must be aware of the need for training and service 
provision.
◆ The aetiology is different, with more emphasis on unwanted 
pregnancy and challenging infant behaviour.
The diagnosis can be facilitated by self-rating questionnaires, but 
the main clinical resource is an interview probing the mother’s emotional response and behaviour. In severe cases and in research, the ‘gold standard’ is direct observation, preferably over a substan-tial length of time.
The treatment proceeds in stages:

◆ Where there is a delay in the maternal emotional response, expla-
nation and reassurance are usually sufﬁ  cient.
◆ When hostility, rejection, and anger are prominent, the primary 
decision is whether to attempt treatment or not. The mother must be given freedom of choice; it is dangerous for her to feel trapped in unwelcome motherhood. At the same time, the father has his rights. The option of relinquishing the infant must be openly acknowledged, and fully discussed with both parents.
◆ If it is decided to embark on treatment (as in most cases), depres-
sion should be treated with psychotherapy, drugs, or (occasion-ally) electroconvulsive therapy.
◆ The speciﬁ  c element of therapy is working on the dyadic rela-

tionship. This relationship, like others, grows through shared pleasure. The baby alone has the power to awaken its mother’s feelings, so the aim is to create circumstances in which mother and child can enjoy each other. It is a mistake to separate the mother and baby completely, which merely compounds the problem by adding an element of avoidance. If there is any hint of abuse or aggressive impulses, the mother must never be left alone with her infant. She must be relieved of irksome burdens of infant care. When mother and baby are calm, she is encour-aged and helped to interact with him—to cuddle, talk, play, and bring out his smile and laughter. Participant play therapy and baby massage may assist.
Treatment can take place in various settings. Home treatment

Treatment can take place in various settings. Home treatment 
can be successful, provided there is enough support to relieve the mother of night care and stressful duties: the maternal grandmother, 5.4 obstetric and gynaecological conditions associated with psychiatric disorder

SECTION 5  psychiatry and medicine 1124
an understanding husband or partner or a family group can some-
times achieve this. Day-hospital treatment provides individual sup-port and group discussion, as well as speciﬁ  c therapies. In the most 
severe and refractory cases, the proper setting is an inpatient mother-and-baby unit, where an experienced team of psychiatric and nursery nurses, available 24 h a day and 7 days a week, can provide full support. Even in the most severe cases, one can feel optimistic about a successful outcome. (For further information about child abuse see Chapter 9.3.3.)
Postpartum psychoses
These fall into two main groups—organic psychoses and bipolar disorders; a third group—reactive or psychogenic psychosis—is most convincingly seen in adoptive mothers and fathers. There are many causes of delirium after childbirth.
(18) Organic psychoses are 
hardly ever seen in Europe or North America, but may still be important in Africa,

(59) India, South-East Asia, and Latin America, 
where the majority of children are born. Historically the most important causes have been infection and eclampsia psychosis, but cerebral venous thrombosis is common in India.
(60)
The form of psychosis still seen in Europe and North America 
was described by Osiander,(61) and illuminated by the case studies 
of Esquirol.(62) The long-standing controversy about its nosology

of Esquirol.(62) The long-standing controversy about its nosology 
has been resolved in favour of a relationship with the bipolar group; but there is also a connection with acute polymorphic (cycloid) psychosis, which may also belong to the bipolar rubric. These are biological brain disorders, with high heritability and an inborn tendency to develop episodes throughout life. The problem of causation can be broken down into three subsidiary questions: the nature of the diathesis, the determinants of clinical polarity (mania, depression, or cycloid), and the trigger that provokes the episode. The ﬁ  rst two questions belong to the wider study of bipolar dis-
order. The third is speciﬁ  c to puerperal psychosis. The clinical facts

order. The third is speciﬁ  c to puerperal psychosis. The clinical facts 
suggest not one, but several triggers related to the female reproduc-tive process—abortion, pregnancy itself (especially the last trimes-ter), the early puerperium (especially the ﬁ  rst 10 days), postpartum 
menstruation, menstruation in general (see menstrual psychosis 
above), and weaning. These triggers can be added to the list of other biological events that trigger bipolar episodes, including surgery, adrenocortical steroid treatment, and seasonal climatic changes. Instances can be given of the combination of all these triggers in the life history of individual women, and there may be a shared pathway in these diverse precipitants. The incidence is somewhat less than 1 in 1000 pregnancies.
(28,63)  The Edinburgh

(28,63)  The Edinburgh 
study showed no link with twin pregnancies, breast feeding, single parenthood, or stillbirth. The miscarriage rate has been low in two studies. This psychosis has high heritability—not just for bipolar disorder, but also the puerperal trigger.
(64)
Postpartum bipolar psychoses are acute, rapidly reaching a climax

(64)
Postpartum bipolar psychoses are acute, rapidly reaching a climax 
of severity. The onset is usually between 2 and 14 days after delivery. Mania is severe, often with ‘schizoaffective’ symptoms or extreme excitement. Almost every psychotic symptom may be seen—the whole gamut of delusions, verbal hallucinations, disorders of the will and self, and catatonic features. There is often an apparent confusion or perplexity. Since the advent of electroconvulsive therapy and neu-roleptic medication, the duration has fallen to a few weeks. A minority of patients show a tendency to relapse in rhythm with menstruation. Puerperal recurrences occur after 20 to 25 per cent of subsequent pregnancies. Non-puerperal recurrences are also common.There are no speciﬁ  c treatments. The ﬁ  rst resource is sedation by

neuroleptic agents, but these should be used with caution because of the risk of severe extrapyramidal side effects, which include neuroleptic malignant syndrome. It is usual to stop breast-feeding, although this may not be necessary, because the infant receives only a minute dose of the neuroleptic and adverse effects have not been noted; Clozapine may, however, accumulate in breast milk. Lithium has been used increasingly since the link with manic-depressive psychosis was recognized. There is also evidence for its prophylac-tic value in women at high-risk. However, it may have adverse 
effects on breast-fed infants. Electroconvulsive therapy is highly

effects on breast-fed infants. Electroconvulsive therapy is highly 
effective in all varieties of puerperal psychosis, including puerperal mania. The location of treatment is an important issue. Since hospitalization can be disruptive to the family, this disorder should for preference be treated at home, where the patient can maintain her role as wife, homemaker, and mother, and her relationship with the newborn; but its severity and the lack of community resources make this a counsel of perfection. If hospital admission is necessary, there are great advantages in conjoint mother and baby admission.
Services for mothers with mental illness
An outline of the services required for this area of psychiatry is slowly emerging. Its aims are prevention in those who are vulner-able, early and accurate diagnosis, and rapid effective intervention, with minimal disruption of family life. These aims require the following:
◆A multi-disciplinary specialist team  This team, a key resource

◆A multi-disciplinary specialist team  This team, a key resource 
whatever the cultural background, should consist of psychia-trists, nursing staff of various kinds, psychologists and social workers; it can serve a population of several million inhabitants, handle severe and intractable illness, train all staff, develop services, and conduct research.
◆A community service  Domiciliary assessment and home treat-
ment are appropriate for mothers.
◆Day care  A day hospital can provide a full range of interventions, 
including groups, play therapy, motherhood classes, anxiety management, and occupational therapy, with minimal family disruption. The presence of mothers with similar disorders is an additional support. The children are cared for in a crèche.
◆Inpatient facilities  Conjoint admission of mother and infant 
is superior to the admission of the mother alone.(65) Wards

is superior to the admission of the mother alone.(65) Wards 
dedicated to conjoint admission also have advantages over admissions to general psychiatric wards, although they are more expensive.
◆An obstetric liaison service  Apart from treating prepartum 
mental illness, this provides an opportunity for preventive psy-chiatry, by detecting vulnerability during pregnancy.
◆Links with other agencies providing services for mothers  The 
social services have a key role. Their family centres fulﬁ  l a similar 
function to mother-and-baby day hospitals. They can relieve the burden on the mother, and safeguard the child, by providing emergency foster care. Other agencies include the National Society for the Prevention of Cruelty to Children (in the United Kingdom), midwifery services, primary care teams, and child psychiatry services.

1125
◆A network of voluntary organizations  These are independent 
organizations, but can have close cordial ties with the profes-sional service. There is no one better suited to support a depressed mother than another mother who has suffered a similar problem and is now well—she knows the stratagems or words of comfort that were helpful, and is living proof of the hope of recovery. For each disorder, a panel of recovered mothers is an important resource.
◆Medico-legal expertise  Expert advice is often required in cases 
of child abuse or infanticide, and where a mother with mental illness is seeking custody of, or access to, her children.
The psychiatry of parental children-killing
The term ‘infanticide’ covers the killing of infants and children by their mother or father in a wide variety of circumstances, broadly divided into ‘neonaticide’ (killing the newborn) and ‘ﬁ  licide’ (the 
later murder of a child).
Neonaticide

Killing neonates (especially female infants) has been customary in certain societies as an ofﬁ  cial policy or ‘grass-roots’ custom for 
controlling population growth. This is completely different from criminal neonaticide, in which a mother, who has concealed her pregnancy and given birth in secret, kills the infant immediately after parturition. This was a major public health problem in Europe during the nineteenth century. Its frequency has dwindled as a result of contraception, a relaxation of the abortion laws, and changed attitudes to single motherhood; but it still occurs.
The mental state of mothers who kill the newborn can be 
deduced from the methods used. Suffocation is by far the most common,
(66) and this testiﬁ  es to the mother’s panic, faced by a cry ing 
baby. In a minority, brutal head injuries, stabbing, or decapitation testify to rage and hatred.
In Europe, starting in Russia in 1647, the public has gradually

In Europe, starting in Russia in 1647, the public has gradually 
taken a humane view of this felony. By 1881, all European states, with the exception of England and Wales, made a distinction between infanticide and other forms of murder, and assigned a more lenient penalty. England and Wales at last came into line with the Infanticide Act 1922. In some American states no distinction is made between this and other forms of murder.
There has been much debate whether the defence of insanity can 
be invoked. Most of these babies die when the mother is in the grip of an emotional crisis—seized by fear or fury. This is not generally acceptable in law as evidence of insanity, which is deﬁ  ned as a 
defect of reason. However, impairment of consciousness undoubt-
edly occurs during labour (see above); it is rare in hospital practice,

edly occurs during labour (see above); it is rare in hospital practice, 
but may be more common in clandestine deliveries, and is hard to exclude. If the defence is burdened with the proof of insanity, there can be no valid evidence in unwitnessed deliveries; but there is the possibility of a miscarriage of justice—that a mother, who killed her baby when her consciousness was clouded, is wrongly con-demned.
Filicide
The majority of murdered children are killed by their parents, and the majority of female murderers kill their own child. A survey in Queensland gave an estimate of the frequency: of 49 infanticides between 1969 and 1978, there were 11 neonaticides and 38 ﬁ  licides; this is about 3 in 100 000 per year of children under 5 years of 
age.
(67) In Sweden, between 1971 and 1980, there were 79 cases 
involving 96 children—an annual rate of 2 in 100 000 children under the age of 5 years.

age.
(68) There are a variety of causes.
◆Depression  This is the most common cause. Studies of convicted 
mothers underestimate the frequency of depressive filicide, because many complete suicide. Melancholic ﬁ  licide is commit-
ted in the belief that the child’s best interests are being served (delusional mercy-killing). Mothers surviving depressive ﬁ  licide 
usually make no attempt to conceal the crime; they confess and seek punishment. Mothers may kill more than one child, but family murder seems more common in men.
◆Child abuse  This is the other relatively common cause. Death 
results from ill-tempered assaults or overzealous punishment, without homicidal intent. Fathers are often involved.
◆Psychosis  In non-affective psychosis, ﬁ  licide may occur if delusions 
involve the child, or as a result of command hallucinations.

◆Trance states  A few ﬁ  licides have occurred during epileptic 
automatism or somnambulism.
Not all parental child killing occurs as a complication of mental 
illness. Unwanted infants are occasionally murdered in cold blood. Euthanasia of an incurably ill and suffering child can also occur.
The only modern texts that cover most of this subject are Motherhood and 
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15, 45–55.5.4 obstetric and gynaecological conditions associated with psychiatric disorder

The coexistence of psychiatric disorders in patients with medical 
illnesses may inﬂ  uence both the diagnosis and the course of the 
illness by their effects on pathophysiological, diagnostic, and thera-peutic processes. There may also be effects on patients’ collabora-tion with treatment and on their relationships with health care staff. Several factors change the management of, medical illnesses and psychiatric disorders, and their inter-relation
◆ increased life-expectancy and increasing survival of people with-
severe illness alter the risk of other medical and psychiatric disorders;
◆ social changes affecting family structure can affect care giving. 
Other social factors include changes in the role of women (work, delayed maternity); increased immigration with conse-quent cultural diversity including different concepts of medical and psychiatric disorders (see Chapter 1.3.2);
◆ increased use of medication in medical and in psychiatric treat-

ment, and changes in the organization of health care and social assistance from hospital-based to community-based.
This chapter describes how to recognize, treat and manage 
psychiatric disorders in medical illnesses.
The frequency of psychiatric disorders 
among the medically ill
The prevalence of psychiatric disorders in medical illnesses ranges 
from 16–60 per cent depending on the research methodology (self-reports or interviews; inclusion or exclusion of somatic items), the setting (out-patient or hospitalized), and the sample. In general, the frequency of psychiatric disorders in patients with heart disease
(1) (coronary disease, heart failure), gastrointestinal diseases

(1) (coronary disease, heart failure), gastrointestinal diseases 
(irritable bowel syndrome), lung diseases (asthma, chronic bron-chitis), and diabetes is 15–20 per cent. In patients with cancer and chronic pain it is 30–40 per cent; and in neurological diseases (Parkinson’s, multiple sclerosis, epilepsy) and dialysis it is 50 per cent. T en to 20 per cent of patients have sub-threshold symptoms 
that nevertheless inﬂ  uence psychosocial functioning. The preva-
lence of psychiatric disorders among family members of people with chronic disabling conditions is only slightly lower. The most 
frequent are organic mental disorders (5–44 per cent), followed by substance abuse (10–25 per cent), anxie ty disorders (10–30 per cent),

frequent are organic mental disorders (5–44 per cent), followed by substance abuse (10–25 per cent), anxie ty disorders (10–30 per cent), 
mood disorders (9–13 per cent), personality disorders (6–9 per cent), somatoform disorders (5–9 per cent), mania and psychosis (1 per cent). Recognition by medical doctors is below 50 per cent and the referral rate to liaison services is approximately 1–3 per cent.
The frequency of medical illnesses among 
psychiatric patients
The most severe psychiatric disorders are frequently associated 
with social isolation, difﬁ  cult relations with health-care providers, 
poor adherence to treatment, unhealthy lifestyle(2) (nutrition, smok-
ing, hygiene), side-effects of medication and substance depend-ence. The presence of psychiatric symptoms can also lead to failure to recognize physical symptoms. And yet some medical illnesses are more frequent in people with schizophrenia than in the general population.

(3)These conditions are cardiovascular r isk (9.4 per cent 
in men, 7 per cent in women), diabetes (13 per cent), hypertension (27 per cent) and chronic conditions in general (41 per cent).
(4)
Table 5.5.1  Prevalence of medical illnesses in patients with mood 
disorders
Disease %
Hypertension 18.1–34.8
Stroke 1.7–1.9Headache 19.3Chronic pulmonary disease 10.6–12.9Hypothyroidism 9.6Obesity 4.6Alcohol abuse 12.2–24.7Nicotine 9.1–12.6Illicit drug abuse 9.75.5
Management of psychiatric 
disorders in medically ill patients, including emergencies

1129
The diagnosis of psychiatric disorder in 
medically-ill patients
Anxiety, fear, demoralization, a sense of loss, decreased pleasure, 
and thoughts of death are frequent in advanced debilitating physical disease even when there is no coexisting anxiety or depres-sive disorder.
Physical disease and its treatment may cause somatic symptoms 
similar to those of psychiatric disorders. And the ‘aetiological’ criterion of the DSM-IV-TR that requires exclusion of a physical cause is often difﬁ  cult to apply in advanced medical illness, as are 
the criteria for depression. Endicott
(5) proposed replacing the four 
somatic items for depression (fatigue, insomnia, weight-loss, and difﬁ culty in concentrating) with four psychological symptoms:

somatic items for depression (fatigue, insomnia, weight-loss, and difﬁ culty in concentrating) with four psychological symptoms: 
depressed appearance, social withdrawal, brooding, non-reactive mood. However, this proposal risks excluding somatic symptoms which are a core manifestation of more severe forms of depressive disorder. In doubtful cases, an inclusive approach to somatic symp-toms is preferable, and the risk of severe psychiatric disorders should not be underestimated.
Self-abasement and guilt are less frequent in medically ill patients. 
In assessing guilt, ethnic and cultural factors must be taken into account, for example, feelings of guilt are uncommon in depressed Arabs, whereas somatization is common. 
Some syndromes in medically ill patients do not correspond 
to standard diagnostic categories but nevertheless inﬂ  uence func-
tioning and the course of disease. The Diagnostic Criteria for Psychosomatic Research

(6) mention illness denial, thanatophobia, 
demoralization, and alexithymia. In medical illness, psychiatric dis-orders may manifest with somatic symptoms (see Chapter 5.2.3).
Table 5.5.2 gives some broad indications for the differential diag-
nosis of psychiatric disorders in the presence of medical illness.
(7)
T o be classed as a psychological reaction, the psychiatric disorder 
must develop at the same time as the onset of the medical illness or the treatment. In some conditions such as, pancreatic cancer, multiple sclerosis, the onset of psychiatric disorder may precede the recognition of the medical illness (e.g. Multidimensional evalu-
ation of the care requirements is essential and codiﬁ  ed approaches 
exist).
(8)
Atypical symptoms occur in psychiatric disorders due to medical

exist).
(8)
Atypical symptoms occur in psychiatric disorders due to medical 
conditions. Drium is often complex with auditory hallucinations 
prevailing, whereas tactile, olfactory, and gustatory hallucinations are rare.
Causes of psychiatric illness among medical 
patients
These are both psychological (see Chapter 5.6). and medical
(see Chapter 5.3. 4.
If properly treated, psychiatric disorders in medically ill patients have the same prognosis as those occurring without medical ill-ness, except in some very advanced and debilitating cases, and in these, the few reported studies give contrasting results. Psychiatric disorders may signiﬁ  cantly inﬂ  uence the outcome of the medical

condition. Depression is associated with an increased risk for subsequent development of ischaemic heart disease, Parkinson’s disease, Alzheimer’s disease (and other dementias) and medical diseases in general. It is an independent predictor of severe compli-cations in diabetes and of mortality in ischaemic heart disease, heart failure,
(9)stroke, dementia, cancer and HIV . Anxiety may 
exacerbate angina, arrhythmia, asthma, movement disorders, hypertension and irritable bowel syndrome and is associated with increased health-seeking behaviour and prescription of inappro-priate drugs.
Delirium is reversible in 70–80 per cent of cases, but in termi-
nally ill patients may be progressive and intractable, and is associ-ated with increased short-term mortality.
(10) Mania and psychosis 
may worsen the medical outcome due to behavioural alterations, poor adherence and increased drug adverse effects.

Table 5.5.2  Differential diagnosis among psychiatric disorders (PD) in medical illnesses (MI)
Comorbidity (MI – PD) Latent (PD) Psychological Reaction Psychoorganic PD
Onset with mi - ++ + /-
Medical aetiology - -/+ - +
Life events - +/- + -
Personal/family medical history ++ --
Cognitive disorders - - - +
Altered awareness - - - +
Fluctuation in severity of psychic
symptoms-- ++
Atypical psychic symptoms - - - +
Self-abasement ++ /- --
Family history for psychic symptoms ++ /- --
Empathy of doctor -/++ /- + -
Response to psychiatric treatment +/- ++ -5.5 management of psychiatric disorders in medically ill patients, including emergencies

SECTION 5  psychiatry and medicine 1130
Treatment
In speciﬁ  c populations of patients such as those with diabetes, 
asthma, myocardial infarction, irritable bowel syndrome, cancer, Parkinson’s disease, multiple sclerosis, and rheumatic diseases, psychosocial interventions and a variety of psychological treat-ments have a positive effect on psychiatric disorders, and the qual-ity of life and relationships.
(11)In medical conditions requiring 
active patient participation, psychological treatments improve adherence to the therapeutic programmes. In diabetes they reduce glycosylated haemoglobin, in Parkinson’s they produce cognitive and motor improvement. Such treatments can reduce physical symptoms including pain, nausea, dyspnoea and disability. For other indices such as mortality in heart attack, longevity in cancer, severity of hypertension and peptic ulcer, and inﬂ  ammatory activ-
ity in rheumatoid arthritis, there are psychological beneﬁ  ts and

ity in rheumatoid arthritis, there are psychological beneﬁ  ts and 
improvements in quality of life but poor effects on medical out-come. Indeed, in the more severe psychiatric disorders, combined treatment with psychopharmacological drugs is more effective. Studies of cost-effectiveness and length of hospitalization have reported conﬂ  icting results.
(12)
The consultation process
(a) Forming an alliance with the medical team
The psychiatrist should initially aim to work with medical staff on 
their clinical rounds, and interview patients who have no psychiat-ric disorder to learn what it means to have the medical condition and to undergo its treatment. The psychiatrist should be present at informal discussions, such as those during coffee breaks,and share the clinical team’s emotional experiences.
(b) Interview with medical team

The aim is to evaluate the clinical situation, review the medical records; identify the most signiﬁ  cant reason for referral and why the consultation has been made at this time; identify the team’s 
approach to the patient, clarify whether the patient has been informed of the consultation and in what way. If the referral seems inappropriate for the patient, does this reﬂ  ect a problem within the 
medical team such as burn out?
(c) Interview with the patient
The interview should move dynamically between the ‘objective’ position (clinical data, psychosocial information) and the ‘subjec-tive’ position. Feelings evoked in the psychiatrist frequently mirror perceptions of the patient and the medical team. T o recognize them helps empathetic relations and emotional containment. A protocol for the interview is shown below.
 (13)
(d) Reporting back to the medical team

(13)
Reporting should be clear and concise with both a verbal and a writ-ten report. The focus should be on the reason for referral. Risk fac-tors and points of strength should be identiﬁ  ed. A verbal report of an 
‘image’ such as an episode fom the patient’s experience, a memory or even a dream can sometimes aid empathetic understanding by the medical team. Practical advice on management should be provided.
(e) Psychopharmacological treatment
The psychopharmacological treatment of medically ill patients may be difﬁ  cult for several reasons including the stigma associated 
with psychiatric disorders, weariness with the many medical treat-ments already undergone, increased sensitivity to side-effects due to pharmacokinetic changes produced by interactions with medi-cal drugs and any underlying liver or renal disease.
(14) However

(14) However 
when adherence is adequate, the therapeutic response is similar to that of patients without medical illnesses. Nevertheless, the pre-scription of medication must not replace receptiveness to the patients problems and emotional support, which are frequently the most effective intervention.
It is often useful to offer the patient a drug not for symptoms 
such as depression when these arise in a discouraging physical situation because this may be seen as disparaging—but for other 
Goal Approach
Overcome stigma The medical team: present the psychiatrist to the patient as a team member and motivate consultation
The psychiatrist: explores any ambivalence or negative feelings empathetically (it may not be clear to the 
patient why a psychiatrist is discussing his/her disorder)
Open questions: background and information Why is the patient hospitalized? What does he/she think of the illness?

Principal emotions and fears What does the patient feel? What is he/she most afraid of?Consider constructive ways of coping; and discuss 
dysfunctionWhat and who most help the patient to overcome difﬁ  culties; who is important, what other resources are 
available
Completing the information Medical history and current quality of lifeDevelop a shared understanding of the situation in 
which medical and psychological aspects are linked 
and not viewed as alternatives.“Normalize” emotional disorders as reactions to illness that may amplify symptoms and inﬂ  uence course.
Describe physical mechanisms of symptom production such as muscular contraction, vasodilation/
constriction, hyperventilation, asthenia, inactivity, immune defences.
Use clear, descriptive language with imagery: e.g. tension is like a tight shoe.

Deﬁ  ning goals and reducing unrealistic expectations Discuss the main problems
Aim to improve problems, not solve them.
Set realistic goals
Propose a treatment plan What interventions, “ﬁ  rst steps”
Practical advice about day-to-day matters such as interpersonal relations, how to reduce tension

1131
realistic goals. The speciﬁ  c contribution that the drug can make to 
achieving these goals should be explained and a clear description provided of its somatic effects. The psychiatrist should also:
◆ Aim to simplify treatment as far as possible. The distinction 
between ‘psychiatric’ and ‘medical’ drugs is arbitrary since many drugs have both physical and psychological effects.
◆ Rationalize treatment using the fewest possible drugs. First choice 
should be drugs that act on more than one symptom, psycho-logical or medical (e.g. reduce agitation and nausea, insomnia and hyporexia, depression and headache, pain and anxiety).
◆ Consider side-effects and interactions before deciding treatment 
including their time of onset. Thus, SSRI should be prescribed at least one week apart from any treatment with signiﬁ  cant gas-

trointestinal side-effects. Investigate complementary drug use: e.g. 20–40 per cent of oncology patients take herbal remedies, many of which have signiﬁ  cant pharmacological interactions 
(see Chapter 6.2.9).
◆ Prefer drugs that were effective for the patient in the past; starting 
with low doses and increasing them gradually.
◆ Sometimes the best action is to discontinue a drug.
Differences from traditional psychotherapy
The major aims are to control distress, maintain self-respect, main-tain signiﬁ  cant relations and doctor-patient communication, work 
through information, and develop adaptive coping mechanisms.
Timing : At times of crisis (e.g. immediately after the communi-

cation of a serious diagnosis), the need for control is paramount. At the onset of complex diseases, short cycles of interviews may prevent subsequent psychiatric disorder.
Flexibility : This is needed due to variations over time in the con-
ditions of treatment (in hospital, or as a day patient or outpatient), the symptoms, and the motivation of the patient, who may alter-nate between the need for emotional sharing and moments of self-withdrawal. Existential uncertainty is reﬂ  ected in relations 
with the psychiatrist and each interview is an entity in itself.
Eclecticism : The complexity of the situation often requires 
integration of different approaches at different times: expressive, cognitive, body-mediated or psycho educational. The intervention

integration of different approaches at different times: expressive, cognitive, body-mediated or psycho educational. The intervention 
may focus on the patient, on family members or on the medical team. Flexibility and eclecticism must originate from the integra-tion of the patient’s needs and the psychiatrist’s empathic and comprehensive evaluation of these needs.
Regression : Illness, hospitalization, fear, and the ‘invalid role’ 
may make a patient, who would otherwise refuse it, become receptive to the psychiatrist’s intervention. During medical illness, emotional defences are more fluid, the relationship with the psychiatrist may form more rapidly and short interventions can be effective. After discharge the psychiatrist must be ready to change approach.
Existential context : A severe disease often casts doubt on the

Existential context : A severe disease often casts doubt on the 
meaning of existence. Patients may fall into despair or ask them-selves what really matters. They may want to reorganize their lives around new priorities. In these circumstances, interviews should focus on the present, abandoning the ‘past-future’ approach, and deﬁ ne the psychiatric disorder as an accentuation of natural human emotions. Fear should be dealt with directly, including fear of 
dying, and the patient’s relatives, including their doctors, should be helped to provide support since fear is greater when experienced alone.
Physical contact : Faced with severe disease, some patients ‘speak’

Physical contact : Faced with severe disease, some patients ‘speak’ 
only after having been touched. Sometimes bodily contact, for example through simple massage, may keep open communication with family members and staff, even without the use of words. A glance, a voice, the sense of touch, or other bodily sensations may form an intense dialogue between patient and therapist and be the most effective way to understand how aware the patient is of his/her condition.
Treatment of urgent situations
◆ Medical treatment should address the overall quality of life, 
including the gap between expectations and reality. Many medi-cal interviews target practical matters but place less emphasis on working through expectations. A doctor-patient relationship capable of offering relief while gradually reducing the gap between hope and reality is fundamental.
◆ The patient’s chief supports are family members and caregivers.

Improving their psychological skills through simple psycho-educational programmes may be more cost-effective than generally increasing psychiatric consultations.
◆ Psychosocial and biological risk factors should be identiﬁ  ed early, 
including both current factors and those in the medical history.
Acute anxiety
Treatment of acute anxiety should maximize the beneﬁ  cial effects of 
the doctor-patient relationship as well as providing speciﬁ  c psycho-

social and pharmacological interventions. At times of crisis, one-on-one companionship is useful, sometimes with simple relaxation or massage that family members can provide. When a serious medi-cal diagnosis is communicated, it is helpful to listen, and for medical staff to be receptive to emotional reactions in the sub sequent 24 hours; solitude should be alleviated, if necessary with the help of voluntary workers. Benzodiazepines should be prescribed only when really necessary and for short periods to reduce the risk of tolerance and 
addiction. Benzodiazepines may reduce respiratory function further 
in patients who retain CO
2, thereby worsening their asthenia. If 
prolonged pharmacological therapy is necessary, sedative antide-pressants may be an alternative to benzodiazepines.

Panic attacks : Somatic symptoms of a panic attack may be 
confused with an excacerbation of medical conditions such as chest pain, irritable bowel syndrome, and asthma. Treatment with a selective serotonin reuptake inhibitor is usually effective but half of these patients require long-term treatment since relapse is common after discontinuation. Psychological treatment
(15) (see 
Chapter 4.7.3) can be effective.
Post-traumatic stress disorder : Stress factors in medical 
contexts may cause and prolong this disorder. Such factors include acute medical events, intensive care, post-confusional reactions, communication of a serious diagnosis, and presence at 
unexpected deaths. Pharmacological therapy has limited results

unexpected deaths. Pharmacological therapy has limited results 
but psychological treatments may be effective (see Chapter 4.6.2), Risk prevention is important.5.5 management of psychiatric disorders in medically ill patients, including emergencies

SECTION 5  psychiatry and medicine 1132
Treatment should be based on prevention, and psycho education, 
psychosocial and pharmacological interventions.
Antidepressants : The choice of drug should be based on the 
side-effect proﬁ  le and interactions (see Chapter 6.2.3). The somatic

side-effect proﬁ  le and interactions (see Chapter 6.2.3). The somatic 
effect of treating depression can be important. Cognitive and motor functions can improve in stroke patients, glycaemic control can improve in diabetics, as can chronic pain, and dyspnoea in lung-disease. SSRIs may produce gastrointestinal side effects, bleeding due to platelet dysfunction, so that monitoring is essential in patients on anticoagulants. Venlafaxine in high doses may increase blood pressure. Mirtazapine has no sexual side-effects, has anti-nausea activity and stimulates the appetite, but may cause weight gain and sedation. TCAs, being anticholinergic, affecting heart conduction and the peripheral autonomic nervous system, are contraindicated in heart disease, cognitive impairment, orthos-
tatic hypotension, hypertrophic prostate, glaucoma and epilepsy.

tatic hypotension, hypertrophic prostate, glaucoma and epilepsy. 
Secondary amines, such as nortriptyline and desipramine, are preferable.
Methylphenidate may be useful in particular medical situations, 
such as palliative care or advanced cancer, to alleviate fatigue, increase appetite, and reduce opiate-induced sedation. It may ele-vate mood and has rapid onset. Agitation and insomnia are the main problems.
Personality disorders, particularly antisocial and borderline disor-ders, may create emergencies due either to aggressive behaviour towards self or others or to conﬂ  ict within the team. Screening for 
substance abuse and depression is necessary since these increase impulsiveness. Patients can become aggressive when their demands are not met, e.g. for increased painkillers, or interviews with their doctors. Staff require support to manage conﬂ  icts and frustration, 
and to maintain a caring approach.
(16)

(16)
Staff must be empathetic but at the same time act as a team. 
Limits and rules should be established at admission treatment to prevent escalation of aggression. Interviews must be in conditions of safety; if necessary with other staff or even police present. The agreed plan must be respected by all staff, avoiding the extremes of excessive permissiveness and excessive rigidity, which may be induced by the patient’s disorder. Patients with personality disor-ders often use truth-based observations pathologically to exploit the therapist’s and institution’s weak points. Recognizing what is true in their criticisms may improve patient management.
Delirium and dementia (see Chapters 4.1.1 and 4.1.13)
Mania 
A manic crisis affects the care of the medical condition dramati-
cally both through excessive activity, weight-loss, reduction of sleep, and through non-compliance with treatment and conﬂ  ict

cally both through excessive activity, weight-loss, reduction of sleep, and through non-compliance with treatment and conﬂ  ict 
with staff. The medical history should be evaluated for disease-related stress factors which may trigger crises. Manic symptoms recognized early together with possible causes of insomnia such as pain, nocturia, dyspnoea, or environmental factors including noise, unsuitable temperature, frequent entrance of night-staff for other patients. Where possible, precipitating factors should be removed. When this is impossible (e.g. a requirement for high-dose cortisone), treatment is as that of mania in other situations

(see Chapter 4.5.8) taking medication side-effects into account (see Chapter 6.2.4). Antipsychotic drugs are generally faster acting at lower doses than in primary mania. More potent antipsychotics are preferable since they have lower anticholinergic and alpha-blocking effects. It is useful to focus on symptoms the patient ﬁ  nds 
disturbing rather than ego-syntonic symptoms. Restraint or hospi-
talization in a psychiatric ward is necessary when hyperactivity 
could compromise physical safety or the underlying condition.
Psychosis
Close collaboration between the psychiatrist and the medical team 
is necessary, with the most appropriate environment for treatment, medical or psychiatric unit, being decided case-by-case. Medical investigations and interviews should be simpliﬁ  ed and clear basic

information provided. Continuity of care among medical profes-sionals is important. The psychological effect of medical treatment should be assessed. When there are hallucinations, medical staff should be educated about their nature and supported, so that they do not criticize any content expressed by the patient, but are able to empathize with the patient’s distress. Management may require constant observation and in some cases restraint and involuntary treatment. Medically ill patients are especially sensitive to the side-effects of antipsychotic drugs but generally respond to lower doses. The choice of drug and dose are based on the side-effects and the 
underlying disease (see Chapter 6.2.2)). Cardiac pathology and 
QTc enlargement require ECG monitoring and ziprasidone, haloperidol, chlorpromazine, and thioridazine are contraindicated. Caution is also necessary in alcoholics, and patients with hypokale-mia and hypomagnesemia.
(17)

(17)
Extra-pyramidal effects of high doses of typical neuroleptics may 
cause laryngospasm and affect the diaphragm, worsening any respiratory insufﬁ  ciency. For chronic treatment, newer drugs are 
preferable. Caution is required in hepatic and renal diseases and where there is a risk of epileptic ﬁ  ts. Fluid intake should be moni-
tored carefully because dehydration increases the risk of neurolep-tic malignant syndrome. In secondary psychosis, the family should be informed and supported and, after the psychotic episode has been resolved, the patient must be helped to work through the disorientating experience.
Aggression and restraint
Aggression should be assessed, thoroughly deﬁ  ning the sequence 
of events that preceded it and the role of medical and psychiatric factors, stressful events and environmental factors. Major predic-tors related to the patient include a history of violence, difﬁ  culty in

communication, and the psychological condition. Predictors related to the environment include: crowding, and a  medical team unreceptive to the patient’s discomfort. The best strategy is preven-tion through providing information in a clear and empathetic way, recognizing risk situations and early signs of agitation, and using de-escalation techniques if necessary with pharmacological sup-port (see also Chapter 11.14).
Environmental measures to limit psychomotor agitation include: 
making the patient as comfortable as possible, reducing back-ground noise, removing potentially harmful objects, and identify-ing situations of which the patients is intolerant. Patients can be

1133
distracted by walking or occupational activities, avoiding a forced 
stay in bed and making the timetable ﬂ  exible. If possible, family 
members can be asked to collaboration.
Where permitted under national law, restraint may become nec-
essary during unmanageable agitation and aggression in the course of an acute psychiatric disorder, in confusional states, especially in the elderly and aftersurgery, with metabolic diseases or during abstinence from alcohol and drugs (seen especially during the ﬁ  rst 
few days of hospitalization).
If restraint is permissible, staff training is necessary because 
improper use may cause injury to patients or staff. Restraint should be used only when strictly necessary and for the shortest possible time, with constant monitoring of its continuing necessity and the patient’s condition.
In medically ill patients restraint may increase the risk of throm-

boembolism, reduce respiratory function with increased risk of infection, increase cognitive deﬁ  cit, pressure ulcers, urinary and 
intestinal incontinence. When restraint is removed there is an increased risk of falls.
Deliberate self-harm and suicidality (see also 
Chapter 4.15.4)
In advanced medical illness, suicidal ideation is frequent as an 
expression of the wish for release from suffering, to regain control over a condition that is perceived as unstoppable, and is wearing the patient down. The actual risk of suicide is slightly above that of the general population. Speciﬁ  c risk factors are: chronic disease, 
uncontrolled physical symptoms such as pain or dyspnoea, disﬁ  g-

uring surgery, unrecognized psychiatric disorder (delirium, depres-sion, personality disorder), substance abuse, and lack of social sup-port. The most frequent form of self-harm is drug overdose, particularly of analgesics and psychopharmacological drugs. Most lethal suicidal acts are of the impulsive type, in particular jumping.
(18)The doctor-patient relationship is often the best help against 
loss of hope. Safety of the environment is crucial since medical contexts facilitate access to potentially lethal objects and to the pos-sibility of jumping. In cancer, the risk is higher in the ﬁ  rst year, 
decreasing with time after diagnosis. In the end stage of illness e.g. in renal failure, treatment withdrawal may have to be considered, with the: clinical and ethical problems of distinguishing a rational decision by the patient from one affected by a psychiatric disorder or another potentially modiﬁ  able factor.

Patients refusing treatment (see also Chapter 1.5.1)
Background culture should be taken into account as some ‘overall 
rejections’ are actually related to this rather than to factors in the individual. An alliance with family members is necessary. Factors in the doctor-patient relationship should be evaluated, together with the information that the patient has received. In some cases refusal relates to fear, anger or despair. If it seems that the patient would feel belittled by a psychiatric consultation it is better to support medical staff who are receptive to the patient’s emotional sate. This is done patients often then accept psychiatric support more readily. In complex cases, the history of the patient’s attitude to treatment should be evaluated on admission to treatment. Aa history of interrupted treatment, changes of doctor or difﬁ  dence towards 
caregivers, may indicate a need for greater efforts to develop good doctor-patient relationships. When obtaining items of medical

caregivers, may indicate a need for greater efforts to develop good doctor-patient relationships. When obtaining items of medical 
history from family members, it is important to identify whom the patient trusts most. In relations with the medical team, the most appropriate ﬁ  gure for dialogue should be identiﬁ  ed. In some cases, 
informal conversations, for example in the evening, are more useful than formal medical interviews.
Levenson, J.L., (2005). Textbook of psychosomatic medicine . American 
Psychiatric Publishing, Washington, DC.
Wise, M.G. and Rundell, J.R., (2005). Clinical manual of Psychosomatic 
medicine: A Guide to Consultation–Liaison Psychiatry . American 
Guthrie, E. and Creed, F. (1996). Seminars in Liaison Psychiatry . College 
seminars series. Royal College of Psychiatrists, London.
Web sites
The European Association for Consultation Liaison Psychiatry and
Psychosomatics. http://www.eaclpp.org

Web sites
International Organization for Consultation- Liaison Psychiatry.
http://www. med.monash.edu.au/psychmed/ioclp.
The International College of Psychosomatic Medicine. http://www.
icpm.org
 1. Rutledge, T., Reis, V .A., Linke, S.E., et al. (2006). Depression in heart 
failure a meta-analytic review of prevalence, intervention effects, and associations with clinical outcomes. Journal of American College of 
Cardiology, 48(8), 1527–37.
 2. Michael, T., Compton, M.T., Daumit, G.L., et al. (2006). Cigarette 
Smoking and Overweight/Obesity Among Individuals with Serious Mental Illnesses: A Preventive Perspective. Harvard Review of 
Psychiatry, 14(4), 212–22.
 3. Carney, C.P . and  Jones, L., (2006). Medical Comorbidity in women

 3. Carney, C.P . and  Jones, L., (2006). Medical Comorbidity in women 
and men with bipolar disorders: a population – based controlled study. Psychosomatic Medicine, 68, 684–91.
 4. Goff, D.C., Sullivan, L.M., McEvoy, J.P ., et al. (2005). A comparison of 
ten-year cardiac risk estimates in schizophrenia patients fromthe CATIE study and matched controls. Schizophrenia Research,
80, 45– 53.
 5. Endicott, J., (1984). Measurement of depression in patients with cancer. 
Cancer, 53(Suppl 10), 2243–9.
 6.  Fava, G.A., Freyberger, H.J., Bech, P ., et al. (1995). Diagnostic criteria 
for use in psychosomatic research. Psychotherapy Psychosomatic, 63(1), 
1–8.
 7. Lipowski, Z.J., (1967) Review of consultation psychiatry and 
psychosomatic medicine, II: clinical aspects. Psychosomatic Medicine, 
29, 201–24.
 8. Huyse, F.J., Lyons, J.S., Stiefel, F.C., et al, (1999). INTERMED: a method 
to assess health service needs. I. Development and reliability. General

to assess health service needs. I. Development and reliability. General 
Hospital Psychiatry, 21, 39–48.
9. Barth, J., Schumacher, M. and Lingen, C.H. (2004) .Depression as a 
Risk Factor for Mortality in Patients With Coronary Heart Disease: A Meta-analysis, Psychosomatic Medicine, 66, 802–13.
10. Breitbart, W., Gibson, C. and Tremblay, A., (2002). The delirium 
experience: delirium recall and delirium-related distress in hospitalized 
patients with cancer, their spouses/caregivers, and their nurses. Psychosomatis, 43, 183–94.
11. Guthrie, E. and Creed, F. (1996). Treatment methods and their 
effectiveness. In Seminars in Liaison Psychiatry (eds. E., Guthrie, 
and F., Creed), pp. 238-73. College seminars series. Royal College of Psychiatrists, London.5.5 management of psychiatric disorders in medically ill patients, including emergencies

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12. Andreoli, P .B., Citero, Vde A. and Mari Jde, J., (2003). A systematic 
review of studies of the cost-effectiveness of mental health 
consultation-liaison interventions in general hospitals. Psychosomatics, 
44(6), 499–507.
13. Stuart, M.R. and Lieberman, J.A., (2002). The ﬁ  fteen minute hour. 
Practical  therapeutic interventions in Primary care . Saunders, Elsevier 
(USA). 14 Levenson JL, (2005). Psychopharmacology. In: Levenson 
JL, ed. Textbook of psychosomatic medicine , American Psychiatric 
15. Shapiro, F. (2001). Eye Movement Desensitization and Reprocessing: 
Basic Principles, Protocols and Procedures . Guilford Press, New Y ork.16. Hay, J.L. and PassiK, S.D. (2000). The cancer patient with borderline 
personality disorder: suggestions for symptom-focused management in the medical setting. Psychooncology, 9(2), 91–100.
17. Gasper, J.J. and  Tsai, C. (2006). Community Behavioral Health

17. Gasper, J.J. and  Tsai, C. (2006). Community Behavioral Health 
Sciences, Community Health Network of San Francisco, San 
Francisco General Hospital, Revised: Guidelines for the use of atypical 
antipsychotics in adults .
18. Druss, B. and Pincus, H. (2000). Suicidal ideation and suicide 
attempts in general medical illnesses, Arch Intern Med, 160(10), 
1522–6.

5.6
Health psychology
Health psychology is concerned with understanding human behav-
iour in the context of health, illness, and health care. It is the study of the psychological factors, which determine how people stay healthy, why they become ill, and how they respond to illness and health care.
Health psychology has emerged as a separate discipline in the 
past 30 years and there are many reasons for its rapid development. An important background factor is the major change in the nature of health problems in industrialized societies during the twentieth century. Chronic illnesses such as heart disease and cancer have become the leading causes of death, and behavioural factors such as smoking, diet, and stress are now recognized as playing a major role in the aetiology and progression of these diseases.
(1) The

(1) The 
provision of health care has grown enormously and there is an increased awareness of good communication as a central ingredi-ent of medical care and of the importance of such factors as patient satisfaction and quality of life as key outcomes in evaluating the efﬁ cacy of medical interventions.
Although health psychology has developed over a similar time 
period to general hospital/liaison psychiatry and shares some com-mon areas of interest, there are some clear differences between these two ﬁ  elds. Liaison psychiatry has a primary focus on hospital 
patients, particularly those experiencing psychological difﬁ  culties 
in the face of a physical health problem. In contrast, health psy-chology has a much broader focus on both healthy and ill popula-tions and on the psychological processes that inﬂ  uence their level 
of health or their degree of adaptation to disease. Whereas health

of health or their degree of adaptation to disease. Whereas health 
psychology has been mainly concerned with developing explana-tions based on theory, for health-related
(2) and illness-related 
behaviour,(3) liaison psychiatry has concentrated on the diagnosis 
and treatment of either unexplained symptoms or psychiatric dis-orders occurring in people with medical conditions (see the other chapters in Part 5 of this volume).
In this chapter we provide an overview of the main themes and 
areas in health psychology. Four broad areas of behaviour will be reviewed, namely behavioural factors inﬂ  uencing health, symptom 
and illness behaviour, health care behaviour, and treatment behav-iour. Inevitably such an overview is selective and the interested reader should seek out a more comprehensive introductory text
(4, 5)
or more in-depth accounts of speciﬁ  c areas.(2, 3)Behavioural factors inﬂ  uencing health
A wide range of behavioural factors can inﬂ  uence health. In the

(4, 5)
A wide range of behavioural factors can inﬂ  uence health. In the 
following section there is a focus on stress, personality, and the main theories that have been developed to explain the variation in health-related behaviours.
Stress and health
The term ‘stress’ is usually used to describe situations, in which individuals are faced with demands that exceed their immediate ability to cope. Stressful situations are typically those that are novel, unpredictable, and uncontrollable as well as those involving change or negative events such as a loss. These situations can give rise to adverse psychological and physiological changes which, in turn, may result in disease.
(6)
Stress may have indirect effects on health by increasing levels of 
risk behaviour (e.g. smoking, alcohol consumption), or may have direct effects on speciﬁ  c physiological mechanisms (e.g. increase in

risk behaviour (e.g. smoking, alcohol consumption), or may have direct effects on speciﬁ  c physiological mechanisms (e.g. increase in 
blood pressure) as well as affecting the individual’s resistance to disease through suppression of the immune system, or by exacer-bating or triggering a disease process in an already vulnerable individual.
A range of behavioural and emotional responses are shown by 
individuals as they attempt to cope with stressful situations and these are accompanied by autonomic, neuroendocrine, and immu-nological changes. During stressful episodes, releasing factors from the brain cause the pituitary to release ACTH which gives rise to the release of corticosteroids from the cortex of the adrenal glands. In addition to producing a number of well-known changes associ-
ated with the mobilization of both short- and longer-term physical

ated with the mobilization of both short- and longer-term physical 
resources (e.g. release of adrenaline (epinephrine) or noradrena-line (norepinephrine), release of glucose, activation of endorphins/encephalins, etc.), these steroids can also have effects on the immune system.
(7)
The effects of stress on immunity have sparked the development 
of the new multi-disciplinary ﬁ  eld of psychoneuroimmunology 
which focuses on the links between psychological, endocrine, and immunological processes (see Chapter 2.3.10). A large amount of work in this area has concentrated on the links between stress and immune function, but less work has focused on impaired immunity and the later development of disease. Acute stressors, such as examinations, or more chronic stressors, such as caring for

SECTION 5  psychiatry and medicine 1136
a dependent elderly relative, have been shown to lead to deleterious 
immunological changes. Work has also associated stress with a greater susceptibility to viral infection
(8) as well as longer healing 
times for experimental puncture wounds(9) and wounds from sur-
gical operations.(10) A recent meta-analysis of studies of stress and 
immunity shows substantial evidence for a relationship between stress and impaired immune system effectiveness, particularly for chronic uncontrollable sources of stress.
(7)
Personality and health
Although there is no consistent empirical support for the older idea that different diseases are linked with speciﬁ  c personality 
types, there is evidence from different, more credible sources that personality factors can inﬂ  uence health and play a role in deter-
mining illness in other ways.
(11)
Probably the best known work in this area concerns the link

(11)
Probably the best known work in this area concerns the link 
between the so-called ‘type A ’ personality and coronary heart disease. The type A personality  was originally characterized by 
competitiveness, time urgency, hostility, and related behavioural factors, which were associated with a signiﬁ  cantly increased risk of 
coronary heart disease (CHD). However, it is now thought that only certain components (e.g. anger and hostility) of the original type A formulation are ‘pathogenic’ .
(12)
Type A individuals show a greater physiological reactivity (e.g.

(12)
Type A individuals show a greater physiological reactivity (e.g. 
in blood pressure and heart rate) to environmental demands and may even generate more demands by their style of behaviour. The more frequent elevations in blood pressure and higher levels of hormonal change, characteristic of this behavioural style, may eventually cause adverse physical changes to the heart and blood vessels. Also, type A individuals are more likely to engage in unhealthy behaviours since they drink more alcohol than type B individuals and, if they smoke, they inhale their cigarette smoke for a longer time.
Type A behaviour is probably the most extensively investigated 
personality factor in current health psychology research, and there have been interventions developed to change the behaviour pat-tern, with positive health outcomes.
(13) More recently the concept 
of the type D personality  has been described as another major psy-

chological risk factor for CHD. Type D refers to the tendency to experience negative emotional states and to inhibit the expression of these emotions in social settings. Type D patients with CHD have been found to have a signiﬁ  cantly higher risk of further cardiac 
morbidity in the short- and longer-term.
(14)
More generally, patterns of positive or negative emotional 
responses, associated with personality, can inﬂ  uence various aspects 
of health.(11,15) Individuals who are high in negative affect (i.e. 
experience more negative emotions, particularly anxiety) do not seem to be more prone to disease, but they are more likely to notice bodily changes and symptoms and consequently seek medical help more frequently (see Wiebe and Smith
(15) for a more detailed 
account of negative affect and the links between personality and health).

Another aspect of personality which has been shown to be health 
protective is optimism, which describes a tendency towards positive expectations in life and which enables individuals to cope better with stressors and engage in healthier lifestyles. There is emerging evidence that optimistic individuals not only cope more effectively with illness and other life crises but also show better health outcomes than those with lower levels of optimism.
(16)Lifestyle and health
The effects on health of behaviours such as smoking and high alcohol use are well documented.
(1) There is overwhelming

(1) There is overwhelming 
evidence that smokers not only are much more likely to die from lung cancer and other cancers but also have much higher rates of cardiovascular disease and chronic respiratory disorders, particu-larly emphysema and chronic bronchitis. Moreover, the disease risk is dose related in that higher levels of smoking are more strongly associated with all these diseases. With sustained high levels of alcohol use a different but equally unpleasant spectrum of health problems can be seen. Drinking is a major cause of accidents partic-ularly motoring accidents and can cause liver damage as well as having detrimental effects on brain functioning.
(1)
For health psychologists, the key questions about health-risk

(1)
For health psychologists, the key questions about health-risk 
behaviours concern their origin, their maintenance, and their prevention or treatment. There are diverse determinants of these behaviours since they may start as ways of coping with stress, in response to peer pressure, for pleasure or for a number of other reasons. Similarly, they will be maintained by a variety of psycho-logical, social, and biological factors.
There are many other risky behaviours that cannot be discussed 
in detail in an overview; these include drug abuse, poor diet, and accidents, and the health effects of all these are also well documented.
(1) Although health psychology has an important role 
to play in describing, explaining, and intervening in all risk behav-iours, these problems should not be conceptualized exclusively in individual behavioural terms since they often reﬂ  ect adverse social 
circumstances or particular cultural contexts.
(17)

(17)
The same caveats about the inﬂ  uence of social and cultural factors 
must also be applied to the understanding of health-protective or health-enhancing behaviours. Prospective cohort studies have conﬁ  rmed that various daily behaviours (e.g. patterns of eating, 
sleeping, and exercise) can have significant long-term effects on health.
(18) For example, there is now a growing body of evidence 
to indicate that regular exercise has a beneﬁ  cial effect on both phys-
ical and psychological health.(19) Exercise can reduce the incidence 
of physical health problems in elderly people and facilitate recovery from heart attack. However, there can be signiﬁ  cant problems in 
ensuring that exercise and other health-promoting activities are adhered to. Interventions need to be planned carefully, because it has been shown that it is usually very difﬁ  cult to make and main-

tain changes in health-related behaviour. Information provision is rarely sufﬁ  cient to promote behaviour change since it is also neces-
sary to elicit and modify beliefs (see below) as well as inﬂ  uencing 
social networks in order to ensure success.
Beliefs and health-related behaviour
Even though health psychologists acknowledge the importance of situational, dispositional, and socio-cultural factors as determi-nants of health-related behaviour, most current research has a primary focus on the role of beliefs in explaining variance in health-related behaviour. The most widely used explanatory approaches have been described generically as ‘social cognition models’ (see Conner and Norman
(2) for an excellent overview of these models).

(2) for an excellent overview of these models). 
These models are based on the premise that, when a person is faced 
with having to make a decision about a particular health behaviour (e.g. attend for a screening test; wear a seat belt, etc.), their decision-making and behaviour can be best understood in terms of their perceptions or beliefs about the health issue and the behaviour in

1137
question. The best known models here are the Health Belief Model, 
Theory of Reasoned Action/Theory of Planned Behaviour, and Protection-Motivation Theory. Broadly these models locate the strength of certain beliefs or evaluations of the health threat (e.g. ‘is it serious? Is it likely to affect me?’) and/or the associated health behaviour (‘Is it an acceptable or worthwhile thing for me to do?’) as the key determinants of an individual’s motivation or intention to carry out the behaviour. More recent models incorporate other beliefs, such as self-efﬁ  cacy, which reﬂ  ect the individual’s belief 
about their ability to implement or carry out the health-related behaviour.
For habitual and addictive health-related behaviours (e.g. dietary 
behaviour; substance abuse) there have also been attempts to develop stage-based models, such as the Precaution Adoption model and the Transtheoretical model
(2) as ways of describing the

(2) as ways of describing the 
stages which people may go through in evaluating the health issue through to thinking about, planning, and maintaining behaviour change. Although these stage models provide a framework for identifying the patient’s state of readiness for a health behaviour change intervention as well as an immediate target for an interven-tion, the evidence for them is weak and there are now a number of serious critiques of their validity and applicability.
(20)
Symptoms and illness behaviour
The psychology of physical symptoms

(20)
Understanding how symptoms are perceived is critical to explain-ing variation in illness behaviour. Psychological factors play an important role in the appraisal of symptoms. There is considerable evidence that bodily symptoms and functions are not perceived with a high degree of accuracy and individuals vary widely in what symptoms are noticed and whether medical help is sought for symptoms.
(21)
The probability that individuals will attend to somatic informa-
tion will depend on the competition for attention from other sources of available stimuli. When the environment is lacking in stimulation individuals tend to pay more attention to bodily symp-toms. Conversely, when an individual’s attention is drawn to the external environment, bodily symptoms are less likely to be noticed. This ﬁ  nding has wide day-to-day applications ranging from why

people cough in the boring parts of movies and lectures to explain-ing demographic differences in symptoms reports, such as increased symptom reporting among the socially isolated and the unemployed. It also has clinical applications in chronic pain and other chronic medical conditions where patients’ isolation may exacerbate the condition by increasing preoccupation with symptoms.
Cognitive schemas can also strongly inﬂ  uence the reporting of 
physical symptoms by guiding the way individuals pay attention to 
their body. Schemas determine the organization of incoming infor-mation and guide health directed behaviour. There is a strong ten-dency for individuals to search for information that is consistent with existing schemas and disregard information that does not ﬁ  t.

Individuals also attach more importance to symptoms consistent with a current cognitive schema than other symptoms. Schemas may develop through personal experience with the condition or by having come across the illness through family, friends, or in the media. Illness schemas can vary from vague ideas about the types of symptoms that represent an illness to more elaborate and detailed conceptions of individual illnesses. Medical students’ disease, where students studying a particular illness notice they 
also have the symptoms of the condition, and episodes of mass psychogenic illness are more dramatic demonstrations of this phenomenon, but the process is seen on a more subtle level with response to placebos (see below). Here, following treatment, a new cognitive schema may shift attention towards symptoms that indicate recovery rather than those of the illness.
Patient delay

There is growing research to suggest that patients’ interpretation of their symptoms can inﬂ  uence help-seeking behaviour.
(22) One 
medical condition where delay can have serious consequences is myocardial infarction, as early arrival at hospital is strongly associ-ated with improved chances of survival. There is a large variation in how long patients delay before seeking help, and a strong predictor of early arrival at hospital is the belief that the symptoms are a heart attack.
(23) Heart attacks are generally seen as sudden and dramatic 
events that involve severe chest pain and collapse. In the case of myocardial infarction patients, the mismatch between these expec-tations and the symptoms experienced gives rise to patient delay.
Research investigating the stages of patient delay for medical 
conditions has generally found three main stages prior to entering treatment, with each stage inﬂ  uenced by a different set of factors

conditions has generally found three main stages prior to entering treatment, with each stage inﬂ  uenced by a different set of factors 
and decisional processes. The ﬁ  rst interval is generally referred to 
as appraisal delay, which is the time period from when the indi-vidual ﬁ  rst detects symptoms to when an illness is inferred. The 
main inﬂ  uences on this period are factors related to interpretation 
of symptoms. The second interval is called illness delay—the period from the time the individual decides he or she is ill until the deci-sion is made to seek medical help. The ﬁ  nal period called utiliza-
tion delay is the time until the individual enters hospital or has 
contact with medical personnel. This ﬁ  rst period of appraisal delay 
has been generally found to cause the largest contribution to over-all delay.
(24)
High health service users

(24)
A large percentage of medical consultations are made for non-medical complaints. This is particularly so for primary health care services. A number of studies have found that a small percentage of individuals without signiﬁ  cant medical illness use a disproportion-
ately large amount of medical services and at considerable cost.
(25)
These individuals have been variously labelled as somatizers, hypo-chondriacs, the worried well, patients with medically unexplained symptoms, and multiple attenders.
Research on high health service users suggests they are higher in

Research on high health service users suggests they are higher in 
trait anxiety. This is consistent with research showing a strong relationship between the somatic complaints and high levels of psychological distress or neuroticism. Individuals high in anxiety tend to be more introspective, watchful for any unusual symptoms, and develop more negative interpretations of symptoms they expe-rience.
(26) Symptoms of anxiety, such as tachycardia, can also be 
misinterpreted as signs of a physical illness by some patients.
Some individuals also seem to have a tendency to make 
catastrophic interpretations about physical symptoms and this may inﬂ  uence frequency of presentation to medical services and 
recovery from illness. Catastrophizing in pain patients has been associated with disability, and drop-out from pain-management programmes.
(27) It has also been associated with higher levels of 
fatigue and disability in chronic fatigue syndrome patients. 5.6 health psychology

SECTION 5  psychiatry and medicine 1138
Catastrophizing is also seen in ‘cardiac invalidism’ . Here patients 
adopt an extremely passive, dependent, and helpless role in the belief that any form of overly vigorous activity will bring on another myocardial infarction. A hypersensitivity to bodily symptoms means that normal sensations may be misconstrued to indicate overexertion or an impending fatal myocardial infarction. This pattern often results in a cycle of inactivity and loss of physical con-dition, which in turn can support these beliefs when patients exert themselves. Many patients who develop highly negative illness beliefs overuse medical services mainly for reassurance about symptoms.
The issue of reassurance in medical consultations is relevant

The issue of reassurance in medical consultations is relevant 
here. One of the common patient expectations in primary care consultations is to have a better understanding of current symptoms. For many patients, being told there is no serious medical problem underlying their symptoms is effective in reducing concern about their condition, but for a signiﬁ  cant number there remains worry 
about their health status. Continued anxiety in this group often results in further needless consultations and investigations. Evidence suggests that patients’ existing beliefs about their condi-tion are predictive of reassurance failure and that for reassurance to be effective, patients’ concerns need to be elicited and appropriate 
information provided to explain either the patient’s symptoms or 
why serious pathology has been ruled out.
(28)
Recent work on improving reassurance following medical testing

(28)
Recent work on improving reassurance following medical testing 
has suggested providing information to patients about the meaning of normal test results before testing, may weaken patients’ preconceived beliefs about their condition and provide a context to help understand the test result. In this study, providing patients with information about normal test results prior to testing, improved their reassurance, reduced their symptoms, and lessened their use of unnecessary medication.
(29)
If patients’ ideas and beliefs about their symptoms are not 
addressed when symptoms persist or recur it is likely that health worry will also be reactivated as the patient still lacks a satisfactory cognitive model or explanation that enables them to interpret their symptoms as benign. A practical consequence of these ﬁ  ndings is

the need for clinicians to elicit the patient’s own attributions and concerns about their symptoms and to use these as the basis for dealing with misconceptions and providing the patient with a more benign explanation of their symptoms.
(29)
Cognitive models of illness
Research suggests patients cluster their ideas about an illness around five coherent themes or components, which health psychologists have called illness perceptions.
(30) These provide a 
framework for patients to make sense of their symptoms, assess health risk, and direct action in the recovery phase. The major cognitive components are as follows.
◆ Identity: the label of the illness and the symptoms the patient 
views as being part of the disease.
◆ Cause: personal ideas about aetiology, which may include simple 
single causes or more complex multiple causal models.
◆ Time-line: the patient’s belief about the likely time course of the 
illness (e.g. acute, chronic, or episodic).

◆ Consequences: expected impact of the illness on the patient’s 
life.◆ Cure/control: the patient’s beliefs about the extent to which the 
illness is amenable to cure or control either through personal actions or by treatment.
These components show logical interrelationships. For example, 
a strong belief that the illness can be cured or controlled is typically 
associated with short perceived illness duration and relatively minor consequences.
The theoretical framework for this research is derived from the 
self-regulatory model developed by Leventhal et al.
(30) This model

(30) This model 
views illness perceptions as critical in guiding the patient’s coping efforts to deal with symptoms, illness, and threats to health. It consists of four components: the cognitive representation of the illness, the emotional response to the illness and treatment, the coping directed by the illness representation, and the individual’s appraisal of the coping outcome.
Patient cognitive models of their illness are, by their nature, 
private. Patients’ are often reluctant to discuss their beliefs about their illness in medical consultations because they fear being seen as ignorant or misinformed. Until recently, assessment of illness perceptions has been by open-ended interviews designed to encour-age patients to elaborate their own ideas on the illness. However, questionnaires have been developed to measure illness perceptions 
in a variety of illnesses

(31,32) as well as speciﬁ  c beliefs about medi-
cation.(33)
The illness perception approach has recently been applied to a 
large number of health conditions (see Hagger and Orbell(34) for a 
meta-analysis). Current research in this area is building on these ﬁ ndings to develop cognitive–behavioural interventions designed 
to modify dysfunctional illness perceptions and provide better recovery. A good example of this is a study showing that the early elicitation and modiﬁ  cation of dysfunctional illness beliefs can 
improve recovery and return to function in patients with a recent myocardial infarction.
(35)
Health care behaviour
In this section we examine the role of psychological processes in the delivery of health care by focusing on two broad areas: doctor–patient communication and health care in hospital.
Doctor–patient communication

There is now considerable evidence not only of patient dissatisfac-tion with medical communication but also of widespread non-compliance with subsequent treatment recommendations. Early research revealed that patient dissatisfaction was often associated with receiving insufﬁ  cient information, poor understanding of 
the medical advice, and subsequent reluctance or inability to follow recommended treatment or advice. Another source of patients’ dissatisfaction is the perception that the doctor lacks interest and empathy, and is unwilling to involve them in decision-making dur-ing the consultation. Thus, an overview of research in this area
(36)
revealed that patient satisfaction was higher following consulta-tions in which the doctor engaged in more social conversation, positive verbal and non-verbal behaviour, and partnership building.
A range of frameworks have been developed for describing the

A range of frameworks have been developed for describing the 
process of the consultation. Similarly various methods have been devised for analysing the interactional processes which occur  during the consultation
(36) and Roter et al .(37) have used these

1139
analyses to propose ﬁ  ve distinct patterns of communication in 
doctors:
◆ narrowly biomedical, characterized by closed-ended medical 
questions and biomedical talk
◆ expanded biomedical, similar to the narrowly biomedical but 
with moderate levels of psychosocial discussion
◆ biopsychosocial, reflecting a balance of psychosocial and 
biomedical topics
◆ psychosocial, characterized by psychosocial exchange
◆ consumerist, characterized by patient questions and information 
giving by the doctor.
The highest levels of patient satisfaction were found with those 
who had seen doctors using the psychosocial communication pat-tern, whereas the lowest satisfaction scores were recorded in those who had experienced either of the two biomedical patterns.
An alternative and broader distinction has been made between 
consultations which are described as patient centred and those which are doctor centred, reﬂ  ecting the extent to which the doctor

consultations which are described as patient centred and those which are doctor centred, reﬂ  ecting the extent to which the doctor 
or patient determines what is discussed. Doctor-centred consulta-tions are ones in which closed questions are used more often and the direction is determined by the doctor, typically with a primary focus on medical problems. In contrast, patient-centred encoun-ters involve more open-ended questions with greater scope for patients to raise their own concerns and agendas.
Patient satisfaction and understanding of their illness following 
the medical consultation can play a major role in inﬂ  uencing adher-
ence with treatment or advice as well as other outcomes including health and well-being. A number of studies have demonstrated ben-eﬁ cial effects on patients’ health and well-being arising from posi-
tive experiences in medical consultations.
(38) These have focused on

(38) These have focused on 
psychological states such as anxiety as well as changes in speciﬁ  c 
physical variables such as blood pressure and blood glucose control. Some of the most impressive ﬁ  ndings here have been found in the 
patient-intervention studies, which are described below.
One important spin-off from the ﬁ  ndings in this area has been 
the development of communication skills training packages for medical undergraduates and for experienced clinicians, particular-ly for improving skills in difﬁ  cult areas of communication such as 
giving ‘bad news’ . There have also been a number of speciﬁ  c inter-
ventions aimed at patients. Generally, these have involved interven-tions for patients prior to a consultation in order to increase their level of participation, particularly to ensure that their own concerns are dealt with and that information provided by the 
doctor is clearly understood.
Health care in hospital

Patients experience many stressors in hospital and these arise 
from a range of factors including enforced lifestyle changes and the demands involved in developing good relations with hospital staff.
(39) Other hospital stressors include worries about aspects of 
communication with staff, as well as concerns about investigations and treatment. Even such factors as the layout and colour of the ward, and the view from the patient’s bed have been found to affect recovery. Not surprisingly, studies that have compared home-treated and hospitalized patients with the same condition have shown less psychosocial distress in those remaining at home.In addition to these general psychological impacts of hospitaliza-
tion, there may be speciﬁ  c problems or demands which occur either

tion, there may be speciﬁ  c problems or demands which occur either 
as a result of the particular health problem or the type of treatment which the patient has to undergo. An example of the way in which patients’ health problems may inﬂ  uence their experience of hospi-
tal care can be seen in some of the studies of patients with HIV/AIDS who may experience negative or blaming attitudes from staff or other patients. For example, with AIDS patients being treated in either special care units or integrated in more general hospital set-tings, the latter group reported higher levels of stress associated with feelings of abandonment, and impersonal or discriminatory treatment. Where staff perceive patients as instrumental in having brought about their own condition through their own behaviour or neglect, they may be less committed, motivated, and sympathetic towards them.
A number of studies have been made of the psychological effects

A number of studies have been made of the psychological effects 
of speciﬁ  c treatment settings such as intensive care units (ICU) and 
haemodialysis units. Studies of patients in intensive care reveal high levels of psychological distress both during and for some time after their stay.
(40) A range of factors seem to be involved, including 
being intubated and not being able to communicate. Even physical aspects of the ICU can have signiﬁ  cant effects. Thus comparisons 
of patients in intensive care units with and without windows found that those in the windowless units were less well oriented during their stay and had a less accurate recall of their length of stay after-wards. In addition to these general problems associated with the intensive care units, other studies have assessed the degree of stress experienced by staff and visitors. For patients’ relatives there is evi-dence that they ﬁ  nd the time spent by the patient on life support in

the intensive care unit particularly worrying. During this time they experience considerable fear and uncertainty but this can be improved by seeking information and the use of other resources.
In contrast with the acute psychological restrictions and demands 
of intensive care, some patients such as those on renal dialysis are 
subject to much more chronic restrictions. Dialysis can have major effects on an individual’s psychological and social functioning, par-ticularly giving rise to vocational impairment, reduced sexual activ-ity, and mood changes.
(41) In addition to the physical limitations 
and demands of dialysis, patients are also faced with the need to adhere to strict recommendations regarding diet and ﬂ  uid con-

sumption, as well as complex medication regimens. A number of aspects of dialysis can give rise to psychological distress, including the constant threat of death, dependence on the dialysis machine and medical staff. The stringent dietary and liquid restrictions are also important factors in patients’ feelings of helplessness and lack of control. The ways in which patients cope can have important inﬂ uences on their well-being and outcome. For example, prob-
lem-focused types of coping have been shown to be associated with better adherence to ﬂ  uid intake restrictions, when these 
coping strategies were used in response to stressors arising from a relatively controllable aspect of dialysis. For those stressors, which 
patients perceived as less controllable, emotion-focused coping

patients perceived as less controllable, emotion-focused coping 
strategies provide better levels of adherence.
Many medical procedures in hospital can give rise to consider-
able discomfort and anxiety. These include certain treatments such as surgery, and speciﬁ  c investigative procedures such as barium 
radiography, endoscopy, and cardiac catheterization, which may 
not only be uncomfortable and sometimes physically distressing but which also carry the threat of uncovering a serious medical 5.6 health psychology

SECTION 5  psychiatry and medicine 1140
condition.(42) Consequently a number of psychological interven-
tions have been developed to prepare patients for surgery or other stressful procedures in the hospital setting. In broad terms they can help by providing the patient with information to reduce the uncertainty of the event, or with speciﬁ  c behavioural or cognitive 
skills to help with some of the discomfort or pain.
(43)
These interventions have been found to improve a range of post-
surgical outcomes, including anxiety, pain and use of pain medica-tion, length of stay in hospital, and various indicators of recovery. All the interventions have been found to be successful in improving at least one aspect of outcome, and the majority of them have a positive impact on many of the outcomes. A meta-analysis by Johnston and Vogele
(43) revealed that the largest recovery effects

(43) revealed that the largest recovery effects 
were obtained for pain, negative affect, and physiological indices of recovery but there was considerable variation in the magnitude of these effects. Smaller but more consistent advantages of psycho-logical preparation were found on pain medication and length of hospital stay. The interventions, which had the most widespread overall effects on all the outcomes, were found to be procedural information provision and behavioural instructions. In addition to these speciﬁ  c psychological preparations, there is now evidence 
that the pre- and post-surgical social setting can have a signiﬁ  cant 
effect on recovery. Studies have also revealed clear beneﬁ  cial effects 
of sharing a room with someone who was recovering from surgery. Patients who had post-surgical room-mates, who had undergone the same type of surgery, have been shown to be less anxious prior to surgery, engaged in more post-surgical physical activity, and

were discharged home sooner.
Treatment behaviour
Patients respond to their treatment in a range of ways and these can 
have very signiﬁ  cant effects on clinical outcomes. Two major areas of 
patient behavioural variation are seen in the extent to which patients adhere to their prescribed treatment and in the non-speciﬁ  c or 
placebo effects of the treatment on clinical outcome. An overview of research on these two areas is now presented.
Adherence
The extent to which the patient adheres to the advice or treatment offered in health care consultations has been widely studied. Most medical consultations result in the prescription of treatment or advice, and the use of medicines is a key aspect to the self-manage-ment of most chronic illnesses. However, many patients fail to do this and low rates of adherence to recommended treatment are seen as problematic in chronic physical and psychiatric illnesses.
(44)
The incidence of reported medication non-adherence varies

(44)
The incidence of reported medication non-adherence varies 
greatly from 4 to 92 per cent across studies, converging at 30 to 50 per cent in chronic illness. In primary prevention studies, it has been found that many participants drop out of lifestyle change programmes, designed to improve diet or reduce health-risk behav-iours. Even patients who have experienced major health problems, such as heart attacks, may show low levels of uptake of rehabilita-tion programmes as well as considerable variation in the adoption of recommended lifestyle change. In the area of mental health, there is also evidence of signiﬁ  cant rates of non-adherence to vari-
ous recommendations from health care providers.
Non-adherence behaviours may be categorized as either inten-
tional or unintentional. Intentional non-adherence arises when the patient makes a strategic decision not to take the treatment as

tional or unintentional. Intentional non-adherence arises when the patient makes a strategic decision not to take the treatment as 
instructed. An example of this type of behaviour has been found among hypertensive patients who believed that they could judge when their blood pressure was high by the presence of symptoms such as stress or headache and thus took antihypertensive medica-tion only when these symptoms were experienced. From a self-regulatory perspective, the level of treatment adherence may be indicative of a strategic coping response, which is entirely consis-tent with the patient’s view of their problem. Thus, patients who believe that their problem will not last for long have been found to be less likely than those with a more chronic time-line represen-tation to adhere to their medication over a long period of time.
Non-adherence may be unintentional when the patient’s

Non-adherence may be unintentional when the patient’s 
intentions to follow treatment recommendations are thwarted by barriers such as forgetting, and inability to follow treatment instructions because of a lack of understanding or physical prob-lems such as poor eyesight or impaired manual dexterity. Thus, if the quality of communication is poor and patients receive infor-mation, which is difﬁ  cult to understand or recall, as has been out-
lined above, then this makes it less likely that treatment will be adhered to.
The determinants of non-adherence

One very obvious explanation for non-adherence arises from poor understanding and recall of information presented in the medical consultation. Many patients lack basic knowledge about their med-ication but there is no simple relationship between this and their adherence. Reviews of adherence research fail to demonstrate a consistent positive association between knowledge and adherence. Moreover, interventions that enhance knowledge do not necessarily improve adherence. Patient satisfaction can act as a mediator between information provision, recall, and adherence since patient surveys reveal that many patients wanted more information than they were given. Dissatisfaction with attributes of the practitioner or the amount of information and explanation provided may act as a barrier to adherence by making the patient less motivated towards treatment.

The emphasis of adherence research over the last decade or so 
has moved away from attempts to identify stable trait factors which characterize the non-adherent patient to achieving a greater under-standing of how and why patients decide to take some treatments and not others. Much of this research is informed by psychological theories, which conceptualize behaviour as the product of cogni-tion which occurs within a social framework.
The application of the social cognition models, described earlier 
in this chapter, indicates that medication non-adherence may arise from a rational decision on the part of the patient and identiﬁ  es 
some of the cognitions which are salient to these decisions. The types of beliefs and attitudes speciﬁ  ed by such theories as the

some of the cognitions which are salient to these decisions. The types of beliefs and attitudes speciﬁ  ed by such theories as the 
Health Belief Model, the Theory of Planned Behaviour and the Self-Regulatory Model (SRM) have all been used to explain aspects of treatment adherence. The SRM also acknowledges the impor-tance of symptom perception in inﬂ  uencing illness representations 
and adherence as a coping behaviour. Conﬁ  rmatory evidence for 
this is provided by ﬁ  ndings from studies of patients with hyperten-
sion and with diabetes, both of whom commonly use perceived symptoms to indicate their blood pressure and glucose levels respectively, and to guide self-treatment. However, patients’ beliefs about their symptoms and estimations of their own blood pressure

1141
and glucose levels are often erroneous, and this can result in poor 
control of symptoms and illness.
More recent research has begun to focus on the role of people’s 
beliefs about medicines and the ways in which these could inﬂ  u-
ence adherence.(45) This research has revealed two broad factors 
describing people’s beliefs about their prescribed medicines: their perceived necessity for maintaining health (speciﬁ  c-necessity) and 
concerns based on beliefs about the potential for dependence or harmful long-term effects and that medication taking is disruptive (specific-concerns). Two factors were also found to describe people’s beliefs about medicines in general. The ﬁ  rst relates to 
the intrinsic properties of medicines and the extent to which they are harmful addictive substances (general-harm) and the second factor comprises concerns that medicines are overused by doctors (general-overuse).
People’s views about the speciﬁ  c medication regimen prescribed

People’s views about the speciﬁ  c medication regimen prescribed 
for them were found to be much more strongly related to adher-ence reports than are more general views about medicines as a whole. Moreover, interplay was found between concerns and neces-
sity beliefs, which suggests that people engage in a risk–beneﬁ  t 
analysis and consequently attempt to moderate the perceived potential for harm by taking less. Patients with stronger concerns based on beliefs about the potential for long-term effects and dependence reported lower adherence rates, whilst those with stronger beliefs in the necessity of their medication reported great-er adherence to medication regimen.
(45) This work points to the 
importance of accessing patients’ beliefs as a prerequisite of any intervention designed to increase medication adherence. In partic-ular, it would seem important to identify speciﬁ  c concerns about 
treatment and to allay these in ways which make sense to the patient.

The placebo response
The term ‘placebo’ is used to describe a treatment that gains a response due to its therapeutic intent rather than the speciﬁ  c ingre-
dients of the treatment itself. Placebo responses have been shown for a wide variety of medical treatments including surgery, psycho-therapy, medication, therapeutic ultrasound, injections, and aero-sol sprays. Placebos have also been demonstrated to have effects in countless medical conditions and also on a number of physiologi-cal functions such as blood pressure, heart rate, gastric motility, lung function, and postoperative swelling. Adverse effects from placebos or so-called ‘nocebo’ effects have also been noted in the literature.
Characteristics of the treatment itself and the setting it is admin-
istered in can have a strong inﬂ  uence on the magnitude of the 
placebo response. In general, treatments that involve more serious

placebo response. In general, treatments that involve more serious 
rituals and sophisticated equipment such as surgery have stronger 
placebo effects. Likewise, other treatments imparting a powerful impression to the patient such as foul- or strong-tasting medicine, injections, and precise instructions also enhance the placebo response. The colour of medication has been shown to have some effect depending on the condition, and known brand names seem to have an edge in placebo response over unknown drug companies.
A similar theme runs through the clinician characteristics that 
increase the placebo response. Clinicians and clinics seen as having high status and having high levels of credibility have an improved placebo response. At the same time, the doctor–patient interaction is also important. If the doctor shows high levels of concern and 
empathy for the patient then the response increased. High conﬁ  -

dence shown by the doctor in the treatment administered to the patient along with a clear indication of the expected response of the treatment is also likely to improve the likelihood of placebo response.
In contrast, isolating characteristics of patients who are placebo 
responders has yielded inconclusive results. Much of the evidence for the role of demographic, intellectual, or personality characteris-tics of patients likely to respond to placebos is mixed and inconsis-tent. Studies have found individuals who responded to placebos in one setting to be unresponsive in another. Likewise, conditioning studies have shown individuals who have been unresponsive can later respond. These ﬁ  ndings point to the fact that individual 
characteristics probably play a less signiﬁ  cant role than situational 
factors and the doctor–patient interaction in influencing the placebo response.

Treatment response has been divided into speciﬁ  c and non-
speciﬁ  c components, with the non-speciﬁ  c component encom-
passing factors such as clinician attention, expectation, reputation, treatment setting, etc. Determining the magnitude of the speciﬁ  c 
and non-speciﬁ  c components of medical treatment is a difﬁ  cult 
and probably impossible task. In an attempt to determine how powerful non-specific effects are under ideal circumstances, Roberts et al.
(46) chose to look at the effect of a number of medical

(46) chose to look at the effect of a number of medical 
treatments later shown to be ineffective but where clinician faith in the treatment was initially positive. Pooling the data from diverse treatments such as gastric freezing for duodenal ulcer and glomectomy for asthma, this study found 40 per cent of patients had an excellent response to the treatments, 30 per cent good, and30 per cent poor. This suggests that under ideal circumstances where clinician and patient expectations are high and the treat-ment is administered in a credible way, non-speciﬁ  c factors can by 
themselves exert a powerful effect.
The role of compliance with placebos also appears to be impor-
tant. In a review of ﬁ  ve placebo-controlled studies measuring both 
compliance with medication and outcome, Epstein
(47) found that

subjects who were more compliant did better on outcome measures, regardless of whether they were on placebo or active treatment. Outcomes included prevention of relapse in schizophrenia, reduc-tion of fever or infection in cancer patients, alcohol abstinence, reduction of weight, and prevention of mortality in patients with heart disease. In a later study, Horwitz et al.
(48) also found the 
risk of death was substantially less in patients who took more than 75 per cent of their medication regardless of whether the medica-tion was placebo or β-blocker. This suggests the act of compliance 
may have some effects of other health-promoting behaviours or cause cognitive or emotional changes that may inﬂ  uence health in 
the long-term.
There have been a number of theories proposed to explain

There have been a number of theories proposed to explain 
the placebo response but no one theory yet provides an adequate integrated theoretical framework. The reduction of anxiety follow-ing treatment and consequent effect on symptoms has been proposed as one mechanism by which the placebo effect may oper-ate, but changes in anxiety states have not reliably been associated with placebo responses. The role of the medical situation and its accoutrements being associated through classical conditioning with symptom relief is likely to play some role. There is, however, little direct research on this proposed mechanism, although 5.6 health psychology

SECTION 5  psychiatry and medicine 1142
classical conditioning of drug responses has been shown in certain 
Two other theories proposed have been the role of cognitive 
dissonance and patient expectations. The cognitive dissonance argument proposes that the placebo effect may be due to the pres-sure on individuals to show consistency in their views and actions. Therefore, for some individuals, having treatment is inconsistent with not showing any change in symptoms and this may encourage the person to reduce this inconsistency. The role of patient expecta-tions and placebo effects is an area that has not received a great deal of systematic research. It is suggested that patient expectations may cause changes in cognitive schemas that inﬂ  uence the types 
and nature of symptoms that patients pay attention to following treatment. New developments in research on illness perception and beliefs about treatment, outlined above, as well as in the ﬁ  elds

and nature of symptoms that patients pay attention to following treatment. New developments in research on illness perception and beliefs about treatment, outlined above, as well as in the ﬁ  elds 
of neurobiology and neuroimaging
(49) hold considerable promise 
for increasing our understanding of the nature of the placebo effect and its determinants.
This selective overview of health psychology has demonstrated the range of psychological processes in health, illness, and health care. At the present time it is primarily a disciplinary area of psychology with an emphasis on research into health and illness behaviour. However, many interventions have been developed for healthy individuals, patients, and health care staff. This practitioner aspect of health psychology is now being accompanied by speciﬁ  c profes-
sional developments, and formal postgraduate training in health psychology is now available in many countries.
(50)

(50)
Health psychology has established itself rapidly but it is still very 
much an emerging discipline. Greater insights are needed into the ways in which psychological processes can inﬂ  uence health and 
illness, and more comprehensive models are required for explain-ing all aspects of health and illness behaviour. In the long term this will result in the increasing use of psychological interventions for preventing and managing health problems and for the effective delivery of health care.
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The organization of psychiatric services for general hospital depart-
ments might change in far-reaching ways in the coming decades. Whereas the focus was primarily on reactive services for inpatients on medical and surgical wards, the future should focus on more proactive integrated service delivery for the complex medically ill. The essential difference from other psychiatric services is that the population served is taken care of by medical specialists in the general health setting. Consequently services are delivered in the context of the medical-psychiatric interface. Consult requests are always formulated in this perspective: the patient is treated for a medical illness or physical complaints and there are signs of an interfering psychiatric disorder.
1 Nowadays these patients are 
referred to as the ‘complex medically ill’ .(1) Therefore triage and 
treatment integrated in the medical context is the area of expertise of consultation-liaison (CL) psychiatrists.

The development of this area of psychiatry has been hampered 
by dysfunctional splits in health care, such as between general and mental health care, both on the level of its organization as well as its reimbursement.
(2, 3) Recent reports, such as the report of the 
joint working group of the United Kingdom Royal College of Physicians and the Royal College of Psychiatrists, which describe the psychological needs of the medically and surgically ill, provide guidance to counteract these dysfunctional splits.
(4) As the delivery 
of care-trajectories for comorbid patients becomes more and more an issue on the health care agenda, CL psychiatrists should seize this opportunity and become advocates for integrated service delivery for the complex medically ill.

1 Whereas in mental health comorbidity refers to making more than 
one criteria based psychiatric diagnosis, in the CL literature the term ‘comorbidity’ is generally used to describe the combination of physical diseases and psychiatric disorders.Current levels of service delivery
Around 1990 the extent of inpatient CL psychiatric service delivery 
was evaluated, based on the records of a representative national sample of hospitals (United States)
(5) and based on a prospective 
multicentred study (Europe).(6) Both studies reported an average 
consult rate of 1 per cent, ranging up to 4–5 per cent in some university settings. This rate is much lower than the prevalence of psychiatric disorders in medical populations.
(6) Taking this under-
utilization into account, the most striking ﬁ  nding was still the large

utilization into account, the most striking ﬁ  nding was still the large 
variation in departments served and types of patients seen. The European Consultation-Liaison Workgroup’s (ECLW) Collaborative Study made clear that CL psychiatric service delivery is primarily an emergency service. Most referrals were late, as reﬂ  ected by an 
average time of 11 days after admission before patients were referred. In addition one-third was emergency referrals: ‘See the patient the same day’ .
(6, 7) Exceptions were the German psychoso-
matic services driven by their primary interest in patients with unexplained physical complaints and problems of coping with somatic illness using a more integrated liaison approach. These ser-vices showed higher consultation rates (between 2 and 4 per cent), provided more follow-up visits, and communication with aftercare providers.
(6, 7–9)
It is now evident that mental disorders and physical diseases

(6, 7–9)
It is now evident that mental disorders and physical diseases 
cluster in vulnerable patients. The prevalence of mental disorders in the general hospital population is on average twice as high compared to that of the general population. However, when focus-ing on speciﬁ  c populations such as cardiac, diabetes, or transplan-
tation, the rates of major depression may reach up to 30 per cent
(10, 11)
(see other chapters of this section). Patients in the general hospital 
setting are primarily treated for their physical diseases. However, 
the multiple interactions between the comorbid medical and psychiatric disorders make them complex. This justiﬁ  es an inte-
grated approach and requires individualized multimodal and mul-tidisciplinary care.
(12,13) These complex patients are the target 
population for CL psychiatrists. They are in need of integrated services.5.7
The organization of 
psychiatric services for general hospital departments
Frits J. Huyse, Roger G. Kathol,

1145
Types of service delivery
Here several models of service delivery are described (Table 5.7.1). 
The models have an increasing level of sophistication determined by their level of integration and the related procedural collabora-tive activities. Service delivery requires by deﬁ  nition, negotiations 
with health plans for their reimbursement. This is especially true for the integrated models of service delivery.
(7,13,14)
Consultations
Consultations are the classical mechanism for doctors to involve other medical specialists in the treatment of patients with addi-tional medical problems. Patients are referred if the treating physi-cian recognizes psychiatric comorbidity or a psychological problem and if he or she thinks that psychiatric evaluation and/or interven-tion may be helpful. The problem linked with this type of service delivery is that physicians often do not recognize psychiatric dis-turbance in medical patients.
(15) In some cases, this problem is

(15) In some cases, this problem is 
avoided by organizing a ‘contract type’ of consultation where every patient with a deﬁ  ned clinical problem is referred, for instance 
patients with attempted suicide.
Liaison2
Whereas in the consultation function psychiatrists wait for the referral, the liaison function is proactive. A preventive approach is implemented through weekly multidisciplinary rounds. In orderto establish such a role the consultant and a departmental head formulate a liaison arrangement for the provision of psychiatric services for a certain population, clinic or ward. An important addi-tional aspect of the liaison model is its educational focus. Though every consult offers an educational opportunity, in the liaison func-tion the consultant is better equipped to enhance the skills of the teams through weekly attendance of clinical rounds. Currently,
2 Here the term ‘liaison’ is only used to describe the speciﬁ  c ‘liaison

2 Here the term ‘liaison’ is only used to describe the speciﬁ  c ‘liaison 
function’ in addition to the basic consultation function.the liaison model is restricted to tertiary care hospitals with 
more extensive CL psychiatric services. In the European collabora-tive study only 5 per cent of the consults came from a liaison arrangement.
(6, 8)
Psychiatric-medical, medical-psychiatric units, or 
psychosomatic units
The ‘Psych-Med unit’ is an integrated clinical service for high 
complex patients with unstable medical disease, such as diabetes, and psychiatric disorders. Due to their mutual interactions such patients require not sequential but integrated assessment and treat-ment, including both intensive medical and psychiatric nursing. Depending on the required acuity levels of physical and psychiatric nursing, different types of Psych-Med units can be described.
(14)

(14)
Dual-trained or combined staffs are selected to provide these levels of integrated care. Organizational prototypes of this function are the US-initiated psychiatric-medical clinics and the Germfan psychosomatic wards, which focus on adjustment disorders in medical patients and complex somatization.
(14) During the last 
years, the efforts to improve integration between inpatient and outpatient care for complex patients led to the implementation of multidisciplinary, and specialized integrated treatment programmes for speciﬁ  c patient groups in day hospitals (e.g. for chronic pain 
patients and geriatric patients).
Screening
As the selection criteria for patients in the liaison function are not operationalized, referrals are intuitively generated on the basis of clinical expertise.
(15) Nowadays instruments are available to sup-

port both clinical work and research. The liaison function can be seen as a precursor of screening. It will gradually merge into more structured preventive functions, deﬁ  ned by the needs of a target 
population and guided by screening.
(16) Currently, two lines of 
screening are in its development. First of all there is a model with a primary focus on psychopathology and primarily depression, using the patient health questionnaire (PHQ) as an indicator of psychiat-ric comorbidity. It is used in (elderly) patients with physical disor-ders, such diabetes, or physical complaints of unknown origin.
(11, 17)
Until now this is mainly used in an outpatient setting. The other approach taken is screening for ‘complexity’ . A European group has taken the approach to operationalize complexity and to develop a screener and an assessment tool to detect and analyse the complex medically ill.
(12,16)  The Complexity Prediction Instrument

(12,16)  The Complexity Prediction Instrument 
(COMPRI)—the screener—is to be applied at admission on an internal medicine ward to detect patients at risk for negative out-comes of care. At the same time a comparable instrument has been developed for the elderly population to detect patients who are frail and are or have an increased risk of becoming complex.
(18) Other 
indicators of complexity such as administrative and clinical are dis-cussed elsewhere.
(12) The INTERMED-method has been developed 
for complexity assessment and the design of related integrated interventions.
(19) It starts with a structured interview evaluating 
16 health risk variables (Table 5.7.2). The ﬁ  tting of these 16 risks

16 health risk variables (Table 5.7.2). The ﬁ  tting of these 16 risks 
with 4 prognostic variables in a biopsychosocial schema and the uniform-scoring system providing different levels of action visual-ized in different colours, supports decision-making and facilitates interdisciplinary communication. The integrated multidisciplinary interventions designed might require case-management.Table 5.7.1  Types of service delivery
1 Emergency services
 • Attempted suicide
 • Acute behavioural disturbances and their prevention
  • Deliria
  • Withdrawal
2  Regular consults for patients with possible interfering psychiatric 
complications, such as anorexia, factitious disorder, anxiety- or depressive 
disorders, adjustment disorders, somatization and organic mental disorders.
3 Integrated services
 •  Participation in multidisciplinary clinics, such as pain, memory, or 
transplant

 •  Participation in multi-disciplinary rounds on ‘liaison-wards’ or of disease 
management programmes, such as for patients with Parkinson disease, 
diabetes, cancer, or chronic heart failure
 •  Screening for depression or complexity in at risk populations, including 
the development of related care trajectories
 •  Clinical services for highly complex patients with both medical and 
psychiatric acuity, such as the medical psychiatric unit5.7 the organization of psychiatric services for general hospital departments

SECTION 5  psychiatry and medicine 1146
Until now this is an area of health care in which mental health 
care is not formally integrated. It is to be expected that screening for psychopathology or complexity in the chronically ill will be become important future tools to initiate integrated care and allow CL psychiatric teams to actively contribute to the care of complex patients.
The organization of a consultation-liaison 
psychiatric service
It is unrealistic to assume that in the future the needs of general hos-
pital patients with psychiatric morbidity can be met simply by 
increasing staff. T o see all patients with psychiatric comorbidity 
would require many times the present stafﬁ  ng levels. Consequently, 
CL psychiatrists should plan their services carefully together with 
their medical colleagues. The following points should be considered.
The population to be seen

Every consultant working in a general hospital, in primary care, or in a nursing-home setting needs to deﬁ  ne what patients have to be

seen and what services are to be delivered. In a general hospital, emergency services will be required for patients who attend for psychological reasons, including attempted suicide, and for patients with substance abuse withdrawal and acute deliria (Table 5.7.1). In addition consults should be done for patients with unexplained physical problems and other complex illness behaviour. The con-sult capacity beyond these two consult categories should be used for the development of more preventive consults integrated in existing forms of multidisciplinary service delivery. Selection of areas of interest depends on several factors, such as service delivery or research priorities of the hospital (for instance transplant or oncology) or an own research agenda. In primary care the target population in addition to the chronically ill will be patients with somatization problems including affective and anxiety disorders 
(see Chapter 5.2.3).
Psychiatric assessment

As in other settings, the formal psychiatric assessment is a crucial part of the services delivered. Speciﬁ  c to the setting is the differen-
tial diagnosis with physical disorders, the role and the meaning of physical deregulations, effects of pharmaca, the effects of the psychiatric disturbance on compliance with the treatment of the physical disease, the consequences of the assessment for the integrated prognosis, and the subsequent long-term integrated management of the patient. As the outcome of psychiatric disor-ders is clearly related to the interfering problems, which contribute to the complexity of patients, inclusion of the assessment of poten-tial risks for such problems should be considered.
(19)
Disciplines and stafﬁ  ng
The size and composition of the CL team needs to be deﬁ  ned 
depending on the size and type of the hospital and of the target group of patients (Table 5.7.1) as well on the ﬁ  nancial possibilities

depending on the size and type of the hospital and of the target group of patients (Table 5.7.1) as well on the ﬁ  nancial possibilities 
and other available services. For the basic function, the assessment and treatment of patients seen for attempted suicide, one is referred to Chapter 4.15.4. In a European study (ECLW Collaborative Study) it became clear that there was a variation in team composi-tion from monodisciplinary (medical model) to multidisciplinary (mental health model) depending on the size of the service as well as the country.
(8) In addition to individual psychotherapeutic treat-

ment, mutual adjustment with and instructions of other caretakers is a key aspect of CL work. Consequently, nowadays CL psychiatry cannot provide optimal care without team members focusing on psychological treatment and the organization of case-management required for long-term individualized care-trajectories. Good evidence is becoming available that psychological interventions (cognitive–behavioural, problem solving, and interpersonal psy-chotherapies) are effective in patients with physical illness and depression as well as unexplained physical complaints;
(20,21) (see 
also Chapter 5.2.3). The effectiveness of interventions of CL psy-chiatric nurses depends on their roles. For the effectiveness of case-management in these patients is less evidence according to a recent systematic review.
(22) Turning it another way around, as CL psychi-

atric nurses will often work in the chronic medically ill, a recent review has provided an overview to assess the effective elements of chronic disease management (Table 5.7.3).
(23) T o be able to con-
tribute to integrated care programmes, such as for diabetes or for haemodialysis, tertiary care hospitals should have teams with, on average, one full-time equivalent of psychiatric staff per 300 beds and a secretary, in addition to psychiatric residents, nurses, and psychologists.
(24) Both psychiatric and complexity screening func-
tions need to be supported by manpower to translate the ﬁ  ndings 
into clinical action, such as the design and implementation of a long-term individualized care trajectory and prevent decompensa-tion in those who are vulnerable.
Relationship between medical staff, hospital board, 
and regional mental health facilities
For the development of more integrated services beyond

For the development of more integrated services beyond 
emergency consultations good working relationships are required. The psychiatrist should be a formal member of the medical staff. Negotiations on the size and focus of CL psychiatric service  delivery Table 5.7.2  Health risks evaluated for complexity assessment with 
INTERMED-method
Chronicity Is patient known with physical illness/disease
Diagnostic dilemma Were physical symptoms clariﬁ  ed

Severity of symptoms Physical functioningDiagnostic challenge Complexity of current medical problemRestrictions in coping Interferences of coping with medical problemsPsychiatric dysfunctioning Psychiatric historyResistance to treatment Capacity to collaborate with treatmentPsychiatric symptoms Severity of symptomsRestrictions in integration Social integration reﬂ  ected by work and leisureSocial dysfunctioning Quality of relationsResidential instability Stability of housingRestrictions of network Availability of helpIntensity of treatment Utilization
Treatment experience Trust in health professionals
Organization of care Participating health professionalsAppropriateness of referral Capacity to deliver appropriate care

1147
should be organized with representatives of the general hospital 
board, the regional mental health provider, and the health plan. They should decide on functions, budgets, and facilities. The lack of medical facilities in mental health institutions is a good reason to include the need to develop a psychiatric medical unit in the general hospital to serve the more serious medically ill from mental health institutions. Wards with both a psychiatric and medical function can solve the problems created by the artiﬁ  cial division 
between general and mental health care.
Audit
Both for ﬁ  nancial purposes as well as for strategic planning practice

Audit
Both for ﬁ  nancial purposes as well as for strategic planning practice 
audit is required. It does not make much sense to have an extensive audit system such as used in studies, unless this is used for projects. Otherwise an audit system integrated in the hospital mainframe seems the most appropriate, including the basic patient documen-tation, the reason for referral, the referring department, their diag-noses, and treatment.
(25)
Training
In the ‘western’ world CL psychiatry is becoming more and more an area of special interest, which is reﬂ  ected in a subspecialty-status 
in several countries, such as the United States, the United Kingdom, and Australia. Training should include speciﬁ  c medicopsychiatric 
aspects of the work, including psychopharmacology in the medi-cally ill. Guidelines have been formulated by several associations and have been published.
(26, 27)

(26, 27)
Associations for consultation-liaison psychiatry exist, which orga-nizational format differs by country. Since the ﬁ  rst decade of the twenty-ﬁ  rst century there is an increasing international exchange 
between leading organizations as well as among leaders in the ﬁ  eld. 
Leading associations are
◆ The Academy of Psychosomatic Medicine in the USA: www.apm.
org. This organization has an international membership and focus and
◆ The European Association of Consultation and Liaison Psychiatry 
and Psychosomatics: www.eaclpp.org
 1. Huyse, F.J. and Stiefel, F.C. (eds.) (July 2006). Integrated care for the 
complex medically ill . Medical Clinics of North America, Elsevier.
 2. Institute of Medicine. (2001). Crossing the quality chasm: a new health

 2. Institute of Medicine. (2001). Crossing the quality chasm: a new health 
system for the 21st century. Committee on quality of health care in 
America . National Academy Press, Washington, DC.
 3. Institute of Medicine. (2005). Improving the quality of health care for 
mental and substance-use conditions: quality chasm series . National 
Academy Press, Washington, DC.
 4. Royal College of Physicians and Royal College of Psychiatrists. (1995). 
The psychological care of medical patients. Recognition of need and service provision .Council report CR35 . Royal College of Physicians and 
Royal College of Psychiatrists, London.
 5. Wallen, J., Pincus, H.A., Goldman, H.H., et al. (1987). Psychiatric 
consultations in short-term general hospitals. Archives of General 
Psychiatry ,44, 163–8.
 6. Huyse, F.J., Herzog, T., Lobo, A., et al. (2001). Consultation-liaison

 6. Huyse, F.J., Herzog, T., Lobo, A., et al. (2001). Consultation-liaison 
psychiatric service delivery: results from a European study. General 
Hospital Psychiatry ,23(3), 124–32.
 7. Huyse, F.J., Herzog, T., Lobo, A., et al. (2000). European consultation-
liaison psychiatric services: the ECLW collaborative study. 
Acta Psychiatrica Scandinavica ,101, 360—6.
 8. Herzog, T., Creed, F., and Huyse, F.J., et al. (1994). Psychosomatic 
medicine in the general hospital. In Psychiatry in Europe: directions and 
developments  (eds. C. Katona, S. Montgomery, and T. Sensky), 
pp. 143–51. Gaskell, London.
 9. de Cruppe, W., Hennch, C., and Buchholz, C., et al. (2005). 
Communication between psychosomatic C-L consultants and general practitioners in a German health care system. General Hospital 
Psychiatry ,27(1), 63–72.
10. Kathol, R., Saravay, S.M., Lobo, A., et al. (2006). Epidemiologic trends

10. Kathol, R., Saravay, S.M., Lobo, A., et al. (2006). Epidemiologic trends 
and costs of fragmentation. The Medical Clinics of North America ,
90, 549–72.
11. Egede, L.E. (2006). Disease-focussed or integrated treatment: diabetes 
and depression. The Medical Clinics of North America ,90, 627–46.
12. De Jonge, P ., Huyse, F.J., and Stiefel, F.C. (2006). Case and care 
complexity in the medically ill. The Medical Clinics of North America ,
90, 679–92.
13. Smith, G.C. and Clarke, D. (2006). Assessing the effectiveness of 
integrated interventions: terminology and approach. The Medical 
Clinics of North America ,90, 533–48.
14. Wulsin, L.R., Söllner, W., and Pincus, H.A. (2006). Models of integrated 
care. The Medical Clinics of North America ,90, 647–77.
15. Söllner, W., DeVries, A., and Steixner, E., et al. (2001). How successful are

15. Söllner, W., DeVries, A., and Steixner, E., et al. (2001). How successful are 
oncologists in identifying patient distress, perceived social support, and need for psychosocial counselling? British Journal of Cancer
,84, 179–85.
16. Huyse, F.J., Stiefel, F.C., and de Jonge, P . (2006). Identiﬁ  ers, or “red 
ﬂ ags” of complexity and need for integrated care. The Medical Clinics 
of North America ,90, 703–12.
17. Kroenke, K. and Rosmalen, J.G.M. (2006). Symptoms, syndromes, and 
the value of psychiatric diagnostics in patients who have functional somatic disorders. The Medical Clinics of North America ,90, 603–26.
18. Slaets, J.P .J. (2006). Vulnerability in the elderly: frailty. The Medical 
Clinics of North America ,90, 593–601.Table 5.7.3  Evidence for effective chronic care management
There is evidence to support the following initiatives
◆ Broad chronic care management models
◆ Integrated community and hospital care

◆ Greater reliance on primary care
◆ Identifying people at greatest risk of complications and hospitalizations
◆ Involving people with long-term conditions in decision-making
◆  Providing accessible structured information for people with long-term 
conditions and their families
◆ Self-management education
◆ Self-monitoring and referral systems
◆ Electronic monitoring and telemonitoring
◆ Using nurse-led strategies, where appropriate
There is less evidence to support the following initiatives
◆ Case-management
◆ Evidence-based care pathways
◆ Shared learning among health professionals
There is limited information about
◆ New models of commissioning services
◆ Appropriate data collection and monitoring
◆ Linking health services with voluntary and community services
(From D. Singh (2006), Transforming chronic care , NHS Surrey and Suffolk UK. © Crown

(From D. Singh (2006), Transforming chronic care , NHS Surrey and Suffolk UK. © Crown 
copyright.)5.7 the organization of psychiatric services for general hospital departments

SECTION 5  psychiatry and medicine 1148
19. Stiefel, F.C., Huyse, F.J., Söllner, W., et al. (2006). Operationalizing 
integrated care on a clinical level: the INTERMED project. The Medical 
Clinics of North America ,90, 713–58.
20. Katon, W.J., Von Korff, M., Lin, E.H., et al. (2004). The pathways study: 
a randomized trial of collaborative care in patients with diabetes and depression. Archives of General Psychiatry ,61(10), 1042–9.
21. Unutzer, J., Katon, W., and Callahan, C.M., (2002). Collaborative 
care management of late-life depression in the primary care setting: a randomized controlled trial. The Journal of the American Medical 
Association ,288(22), 2836–45.
22. Latour, C.H., van der Windt, D.A., de Jonge, P ., et al. (2007). Nurse-led 
case management for ambulatory complex patients in general health care: a systematic review. Journal of Psychosomatic Research ,62(3), 
385–95.
23. Singh, D. (2006). Transforming chronic care . NHS Surrey and

385–95.
23. Singh, D. (2006). Transforming chronic care . NHS Surrey and 
Suffolk, UK.24. Herzog, T., Stein, B., Söllner, W., et al. (2002). Practice guidelines for 
consultation-liaison psychosomatics . Schattauer, Stuttgart.
25. Söllner, W., Stein, B., and Hendrischke, A., et al. (2005). 
A documentation form for the consultation-liaison services: development of the CL-BaDo. Zeitschrift fur Psychosomatische 
Medizin und Psychotherapie ,51, 310–22.
26. Gitlin, D.F., Schindler, B.A., Stern, T.A., et al. (1996). Recommended 
guidelines for CL psychiatric training in psychiatry residency programs: a report from the academy of psychosomatic medicine task force on psychiatric training in CL psychiatry. Psychosomatics ,37,
3–11.
27. Söllner, W., Creed, F. and the EACLPP Workgroup on training 
in CL. (2007). European guidelines for training in CL psychiatry and psychosomatics. Journal of Psychosomatic Research ,62(4), 
501–09.

6.1 The evaluation of treatments  1151
1242
Max Fink

1242
Max Fink
Philip J. Cowen6.2.10.3 Transcranial magnetic stimulation   1263
Diana Sanders
 6.3.2 Cognitive behaviour therapy  1285
 6.3.3  Interpersonal psychotherapy for

1337
Michael CroweSECTION 6
Treatment Methods 
in Psychiatry

6.3.8  Family therapy in the adult 
psychiatric setting  1380
W. Rössler
Kevin Gournay 6.4.3  Social work approaches to mental health work: international trends  
1408

6.1
Contents
 6.1.1 The evaluation of physical treatments
 6.12 The evaluation of psychological treatment
Paul Crits-Christoph and Mary Beth Connolly Gibbons
6.1.1 The evaluation of 
physical treatments
The strengths and weakness of the 
single trial
Strengths
New treatments, or variations of older therapies, rarely represent 
a revolutionary departure from what has gone before. As progress is usually made in modest steps, evaluation in prospective rand-omized trials is needed. These studies, comparing a new treatment with a relevant control, may be able to highlight and quantify relatively subtle but important differences in outcome.
Randomization controls for selection biases. If undertaken care-

fully, it should ensure that both known and unknown confounding variables, such as age, sex, and additional medications, are evenly distributed between groups. Any differences in outcome should then be due to the treatment, or the intention to give the treatment (see below). In 1991, the World Health Organization stated that the randomized controlled trial, if ethical and feasible, is the most objective means of evaluating mental health interventions.
(1)
Certainly, large well-conducted trials, with participants, inter-
ventions, and outcomes recognizable to those working in health services, are potent guides to clinical practice. Nevertheless, even when such trials exist, it is important to view them alongside all other comparable evidence. Should the large study afﬁ  rm the 
ﬁ ndings of smaller trials the clinician can proceed with conﬁ  dence. If there is a discrepancy then debate will be generated, which should

ﬁ ndings of smaller trials the clinician can proceed with conﬁ  dence. If there is a discrepancy then debate will be generated, which should 
clarify important issues relating to the participants, interventions, or outcomes measured or to the methods by which the trial was conducted.
(2)
Power
As numbers within a study increase so does the precision of results, enabling important but subtle differences to be detected, if they do indeed exist. Should a new treatment be considerably better than its predecessors few people would have to be randomized in order to demonstrate clearly the advantage of the innovative approach. As the advantage expected of new treatments is usually modest, reasonably large studies are often needed.
The power calculation is an important prerequisite for any rand-

omized trial. For example, if clinical observation suggests that a new treatment can help 20 per cent more people avoid admission than the standard care, this can form the basis for a power calculation for a trial. Using a simple formula
(3) the trialist can work out how many 
people would have to be randomized in order to have a known prob-ability of highlighting such a difference, should one really exist. In this case, about 150 people would have to be allocated to each arm of the trial to be reasonably conﬁ  dent of detecting a true 20 per cent 
difference ( α= 0.05, β= 0.8). Most mental health trials are far too 
small to show up anything but very gross differences between treat-ments. For example, the average number of participants in schizo-phrenia trials is about 100 with only a slow increase over time.
(4)
A single small trial should not greatly inﬂ  uence the clinician, but

(4)
A single small trial should not greatly inﬂ  uence the clinician, but 
the combined results of several studies may begin to have the power to inform practice.
Biases
Randomization attempts to control for the biases that would inﬂ  u-
ence treatment allocation (selection biases). Blinding at outcome attempts to control for biases that would result from participants or raters knowing which treatment had been allocated to whom (observer bias). Inadequate randomization leads to an overestimate of effect in the region of 31 to 40 per cent, and poor blinding at outcome to that of about 17 per cent.
(5) Further overestimate 
results from the use of unpublished or modiﬁ  ed scales, commonly 
seen in mental health studies, and a ﬁ  nancial or academic invest-
ment in the therapy by the trialists.(6, 7)The evaluation of treatments

SECTION 6  treatment methods in psychiatry 1152
There are many threats to the validity of a single trial. Viewing all 
relevant studies, each of which was subject to different degrees of bias, should give a more balanced picture. Of course, the reader of a review should be vigilant for the systematic bias, across all trials, that may consistently sway results one particular direction.
Generalizability
Even if a study is adequately powered and undertaken with due regard for bias, a single trial may be difﬁ  cult to apply to everyday 
practice.
(a) Participants
Most studies involve unusual participants. Frequently those eligible for trials have to give informed consent, their problems are well deﬁ ned and do not involve multiple pathologies, and they are 
expected to tolerate the demands of a study.
(b) Interventions
Applying the results of a single study is made even more difﬁ  cult

Applying the results of a single study is made even more difﬁ  cult 
because study interventions are often impractical. For example, drug trials may use rigid dose regimens impossible to apply to routine care. Psychosocial therapies tested within a trial are often of such high quality that they bear little resemblance to what an overstretched clinical service can provide.
(c) Outcomes
Measurement of outcome may also limit the value of a single trial. In a survey of 2000 schizophrenia trials, 640 different scales were used to record outcomes such as mental state, behaviour, global impression, and adverse effects.
(4) Speciﬁ  c subspecialties within 
psychiatry may have an even greater propensity to create scales for trials.
(8) Even within poorly powered trials, these sensitive tools 
may be able to detect real differences between treatments that may be statistically if not clinically signiﬁ  cant. However, few clinicians

may be able to detect real differences between treatments that may be statistically if not clinically signiﬁ  cant. However, few clinicians 
use such scales in everyday practice and interpreting results becomes a matter of conjecture.
Trials that involve carefully defined groups of participants 
receiving meticulously controlled treatments and having outcomes measured on sensitive scales are called ‘explanatory’ studies.
(9) Such 
trials dominate the literature, although calls for more pragmatic or ‘real world’ methodology are increasing
(4,10) and there are now 
examples of this broader approach.(11, 12, 13, 14)  Currently, general-
izing from the results of a single trial to day-to-day practice is inadvisable. If, however, several explanatory studies, all undertaken with constrained, but different, methodologies are giving a similar result, the clinician can feel a little more comfortable when acting on their ﬁ  ndings.
The rogue result

Even the well-conducted generalizable trial can produce a rogue 
result. Currently, the acceptable level of chance is one in 20. A statistically signiﬁ  cant result, often denoted as p<0.05, suggests that 
the ﬁ  nding, if the experiment was to be replicated, should occur 
19 out of 20 times. One time in 20, however, a different result will appear simply because of chance. This can lead to an interest-
ing paradox. A single trial may not provide the best evidence of how to manage people, even in the locality that the study was undertaken. The play of chance may result in an erroneous result and unless that trial is viewed in the company of all relevant evidence, clinicians will be mislead.Time

It is inadvisable to act on the results of a single trial because of issues of power, biases, generalizability, and the possibility of chance erroneous results. There is, however, also the issue of time. Clinicians may often prefer to read the results of a single review rather than spending time assimilating information from several similar trials. Most practitioners have very little time to keep up with research relevant to their practice. Clinicians admit to having half an hour of reading time per week,
(15) and much of that may 
not be retained.(16) Reading reviews is time efﬁ  cient.
Reviews
There are two main approaches to the reviewing process—the 
traditional and the systematic.
The traditional review
The traditional review is often undertaken by a person well respected in the relevant ﬁ  eld who uses knowledge and acumen,

The traditional review is often undertaken by a person well respected in the relevant ﬁ  eld who uses knowledge and acumen, 
supplemented by research, to produce a synopsis of the literature. This approach still dominates the current texts, journals, and lec-ture tours. For example, in 1987 in four major North American medical journals, 86 per cent of review articles depended on quali-tative synthesis and contained no ‘methods’ section whatsoever.
(17)
In only 6 per cent of the reviews was quantiﬁ  cation attempted in 
order to support opinion and the situation did not improve much across the next decade.
(18) Therefore, the clinician is left in a situa-
tion where it is difﬁ  cult not to operate under a double standard. On 
the one hand, a large relevant trial providing objective evaluation would be desirable, but frequently, a traditional subjective review is all that is available.
Systematic reviews

The form of a systematic review encourages the introduction of basic epidemiological principles and quantiﬁ  cation into the 
process of reviewing. Gene Glass, an educational psychologist, was the ﬁ  rst to add the results of similar studies in the hope of quantify-
ing the effects of a treatment.
(19) Glass deﬁ  ned ‘meta-analysis’ as 
‘the statistical analysis of a large collection of analyses results from individual studies for the purpose of integrating the ﬁ  ndings’ .
(20)
Unsurprisingly, in the sensitive area of the psychotherapies, 
their ﬁ  rst and ﬂ  awed attempts in the new discipline generated 
controversy.(21) Critics were quick to point out that drawing con-

clusions from summation of very different types of therapies, undertaken by practitioners of varied experience, was likely to be inadvisable. These pioneers, who even years later are still being criticized for adding ‘apples and oranges’ ,
(22) are nevertheless owed 
a great debt by the rest of medicine. After all, it depends on the question being asked. It is ﬁ  ne to mix apples and oranges, if your 
question is about fruit.
(23)
Systematic reviews attempt to minimize bias in the identiﬁ  ca-

(23)
tion, extraction, and summation of relevant data by applying good survey methods to the process of literature reviewing. An analogy may help. In a community survey of the prevalence of mental disorders, a researcher stands on the doorstep of the hospital and suggests that 5 per cent of the population suffers from serious mental illness. By chance, the ﬁ  nal estimate may even be correct, 
but the work could not be seen as methodologically rigorous. The 
researcher should have written a study protocol, clearly deﬁ  ned an

1153
unbiased sample of individuals to interview, and speciﬁ  ed a priori 
the analyses to be undertaken. A systematic review should do this for a survey of a ‘population’ of relevant literature. Within such a review, the objectives, criteria for selection of relevant studies, search strategy, methods of study selection, data extraction, and assimilation are all made explicit.
The advantages of the systematic approach
As is suggested above, a systematic review may, by adding the results of similar studies together, at least begin to address the issue of the underpowered study, single trials of biased methodology, poor generalizability, and idiosyncratic results. Although often longer than most traditional reviews, the systematic review is still a time-efﬁ cient way to appraise research. Additional advantages are both 
intuitive and practical.
(a) Objectivity
Medicine remains a scientiﬁ  c discipline and the attempt at objective

Medicine remains a scientiﬁ  c discipline and the attempt at objective 
quantiﬁ  cation must be an integral part of this approach. However, 
the systematic review and meta-analysis should never become a source of clinical tyranny. Individual clinicians will always have to use wisdom and judgement in their day-to-da y decision-making, 
but to exclude objective appraisal from this process is foolhardy.
(b) Clinical empowerment
Systematic reviews can provide clear information to clinicians, policy makers, and recipients of care, and so help inform the decision-making process. For example, a systematic review of family therapy suggests that this educational, psychosocial package can help those with schizophrenia avoid or postpone relapse.
(24) This ﬁ  nding is 
very much in line with the suggestions of traditional reviews.(25)

However, the systematic review is able to illustrate how seven fami-lies have to undergo regular therapy, for up to a year, in order for a single relapse to be postponed. Such data, of course, mean different things to different people. Clinicians may ﬁ  nd this an acceptable 
degree of effort, whereas managers of services, or even families of those with schizophrenia, may not. Although the ﬁ  ndings may not 
decrease controversy, at least debate can be informed.
The quantiﬁ  cation of trial data can sometimes provide informa-
tion quite at odds with the advice of traditional reviewers. The best example comes from outside mental health care. In 1992, Antman et al. undertook a meta-analysis of randomized trials evaluating the 
care of those with acute myocardial infarction.
(26) As the reviewers

(26) As the reviewers 
added trial data, they found that by 1973 enough studies existed to show clearly that thrombolytic treatment saved lives. Subsequent trials added precision to the result but did not change the ﬁ  nding. 
Antman and colleagues also showed how traditional reviews contin-ued to fail to mention thrombolytic therapy up to 15 years after the summated trial data could have shown its value.
(26) These traditional 
reviews recommended treatments for myocardial infarction that were positively harmful. Examples have emerged from mental health. Sometimes, traditional reviews make bold claims or recommenda-tions which are not supported by the evidence in quantitative, systematic reviews. For example, some claims made for cognitive therapy for schizophrenia
(27) go well beyond objectively summarized 
evidence.(28, 29) Conversely, even when evidence is of high quality

evidence.(28, 29) Conversely, even when evidence is of high quality 
and readily accessible, traditional reviewers can be blind. For exam-ple, both the strengths and the limitations of new generation antip-sychotic drugs have been evident for years
(30,31,32) but traditional reviews and texts have encouraged uncritical enthusiasm for their 
use(33, 34) and even guilt for failing to prescribe.(35)
(c) Gaps in research
Often a systematic review will highlight unsuspected gaps in research. The trial-base of much routine practice is not strong, and systematic reviews can help shape questions to be tested in well-planned and conducted trials.
(36) Certainly, some research 
funders are now requiring that a systematic review be undertaken before a randomized trial is funded. This also avoids wasting resources on questions that have already been answered.
The limitations of the systematic approach
(a) Qualitative information

Systematic reviews focusing on the value of treatments given to those with mental health problems usually involves quantitative synthesis of data from randomized trials. Incorporating the great wealth of information from more qualitative approaches in an unbiased way is problematic.
(b) Trial content and quality
Systematic reviews are limited by trial content and quality. For example, it is feasible that, on average, those taking a new drug may have a statistically signiﬁ  cant 10-point-greater decrease in a modi-
ﬁ ed Brief Psychiatric Rating Scale
(37) score than those taking the 
comparison treatment. First, this ﬁ  nding is difﬁ  cult to put into

comparison treatment. First, this ﬁ  nding is difﬁ  cult to put into 
clinically meaningful terms. Second, most scales do not provide ‘interval’ data. A 10-point change for someone who started with a very high score may not mean the same as the same change for a person entering the study with a lower rating. Third, more prob-lems stem from the modiﬁ  cation of the scale. This may well not be 
published and so validity is questionable. The use of such data is associated with an overestimate of effect.
Undertaking a systematic review of poor-quality trials is an 
important prerequisite for the design of good studies, but clinical interpretation can be problematic.
(38)
(c) Rare outcomes

(38)
Randomized trials are not a powerful means of identifying rare but important outcomes. For example, large cohorts of those taking the ‘atypical’ antipsychotic drug, clozapine, suggest a rate of about 1 per cent for agranulocytosis, a serious adverse effect.
(39) However, 
a systematic review of all relevant randomized trials ﬁ  nds a much 
lower incidence.(40) As the most vulnerable period for the occur-
rence of agranulocytosis is from weeks 6 to 18 of treatment,(39) and 
most studies in the systematic review were of shorter duration, the incidence was underestimated.
Trials have limited power to identify rare outcomes and, although 
systematic reviews may increase this power, reviews of studies of different methodologies may be needed to quantify these important effects.

(d) Limited statistical methods
The statistics used to summate data within meta-analyses are still evolving. For example, much of the continuous scale data, seen so frequently in mental health trials, is not normally distributed. How robust the commonly used methods of meta-analysis are for these non-parametric data is not clear. In addition, as mental health begins to evaluate preventive interventions then cluster randomi-zation, where communities or institutions are randomized rather 6.1.1 the evaluation of physical treatments

SECTION 6  treatment methods in psychiatry 1154
than individuals, will become more common. The statistics for 
a meta-analysis of these studies is still a matter of debate.(41)
Frequently, a systematic review of mental health trials must present, but not summate, relevant data.
The methods of systematic reviews
Setting the question
Clinical questions regarding the effects of treatments have three parts: the participants (who are the people of interest to the questioner?), the interventions (what are the speciﬁ  c treatments

Clinical questions regarding the effects of treatments have three parts: the participants (who are the people of interest to the questioner?), the interventions (what are the speciﬁ  c treatments 
that are to be the focus of the review?), and the outcomes (what are the outcomes of interest to the reviewers?) . Although the reviewers may have knowledge of existing trials and their limitations, it is important that the questions set are relevant to the review’s reader-ship. If the review is to service clinicians then clinically relevant outcomes must be a priority and not necessarily those anticipated by foreknowledge of the trials. If all studies then provide data on mean change in the Brief Psychiatric Rating Scale and fail to men-tion the outcome of ‘clinically important improvement’ , the review can highlight this important gap in knowledge.
Developing an answerable question. The next stage for formulat-

ing the question is to decide on the type of study that is best suited to answering the question. For questions related to the efﬁ  cacy of 
treatments this is usually the randomized trial. At ﬁ  rst glance, this 
may seem straightforward, but it is important to state a priori
whether studies that implied, but did not state, randomization should be included. No other methodological parameter is so consistently linked with exaggerated estimations of effect than poor description of randomization.
(5) Studies that describe themselves 
as ‘prospective, double-blind, evaluative controlled trials’ would be excluded from a review if the entry criteria demanded an explicit description of randomization.
Identifying studies
Studies are usually identiﬁ  ed by searching bibliographic databases 
such as EMBASE, MEDLINE, or PsycINFO. Hand-searching relevant journals, conference proceedings, and references is also often undertaken.

A systematic review would be a misnomer if the researchers 
did not make the means of identiﬁ  cation of studies clear and repro-
ducible. The exact source of trials, and the search strategies, must be explicit. It is at this poin`t that the advice of an information specialist is important. The coverage of mental health journals in many bibliographic databases is poor and often limited by region or language
(42) so that searching several sources is advisable. For 
example, the last decade China has become highly productive of mental health trials
(43) but few are reported in mainstream biblio-
graphic databases.(44)
In recent years, however, the situation for those wishing to iden-
tify all treatment trials relevant to a particular topic has become easier. The Cochrane Controlled Trials Register within the Cochrane Library,

(45) is the largest and most comprehensive bibliographic 
database of published and unpublished randomized trials, and controlled clinical studies, in existence. For citations of trials, this specialist register has eclipsed databases such as EMBASE, Medline, and PsycINFO. Searching the Cochrane Controlled Trials Register also avoids the problem of the numerous ‘false’ positive citations produced by searches of unspecialized biomedical databases.Identifying every possible study is important. Potent biases 
operate in this area. Trials that have statistically signiﬁ  cant results 
are more likely to be published than those reporting equivocal ﬁ ndings,
(46) and they are more likely to be published in English.(47)
Systematic reviews incorporating only Anglophone published data

Systematic reviews incorporating only Anglophone published data 
or trials from one region are likely to produce, at best, imprecise, and at worse, overoptimistic views of efﬁ  cacy.
Selecting studies
Once a search is completed, relevant studies must then be selected 
without bias. Reviewers usually work independently and document the outcome of all disputed decisions. Some feel that those select-
ing the trials should be blind to the study’s author, source (usually a journal), and the institution where the trial was undertaken. All 
have potential to bias the study selection. However, such blinding would often involve prohibitive effort. In any event, a systematic review should make explicit the degree of effort made to avoid selection bias at this crucial stage.
Quality assessment of trials

Once studies are identiﬁ  ed and prespeciﬁ  ed entry criteria met, 
a last set of quality criteria may be applied. Scales are available, but essentially they rate selection and observation bias (see above). The description of concealment of allocation is central, as this meth-odological parameter has consistently been shown to be linked with an estimate of effect. If this is poorly reported, the trial is likely to overestimate the effect of the experimental intervention.
(5) For 
trials that describe allocation with nothing more than ‘randomized’ , this single parameter may not be a sensitive measure of quality. A scale addressing both selection and observation bias by rating the description of randomization, blinding, and reasons for people withdrawing, may be more appropriate.
(48)
A systematic review should prestate the level of quality that is 
acceptable, or, at the very least, how the data from poor-quality studies are to be managed.
Data extraction

(48)
Reliable data extraction is important. Just as studies must be selected with due regard for the inclusion of bias, so data must be extracted carefully and reproducibly. Often reviewers ensure maximum reliability by organizing double data extraction by an independent reviewer.
Data management
(a) A priori  primary analysis
As with any quantitative research, a systematic review will generate 
the potential for multiple analyses. As one in 20 will be statistically signiﬁ  cant by chance, it is important to state a priori  the primary 
analyses to be undertaken. Although multiple secondary analysis are often undertaken, these are only hypothesis-generating as data have been multiply tested.
(b) Unacceptable loss to follow-up

In every study, there must be a certain attrition that renders data meaningless. For example, in a trial of tacrine for those with Alzheimer’s disease 68 per cent of people taking the experimental compound were withdrawn or lost to follow-up.
(49) Drawing 
conclusions from the data provided by the 32 per cent of ‘compl-eters’ is problematic as selection bias, originally addressed by

1155
randomization, is likely to be great. Trial attrition may not be 
immediately apparent from ﬁ  rst glance. For example, a meta-
analysis of studies comparing the antipsychotic quetiapine with chlorpromazine and haloperidol for schizophrenia shows consid-erable loss to follow-up at only a few weeks.
(50) The last observa-
tion of those leaving was carried forward to the results, so that data presented in the trials were on the numbers originally randomized. The trialists made an assumption that data collected just before leaving the study would reﬂ  ect the situation at the end of the trial. 
These assumptions by the trialists may or may not be justiﬁ  ed
(51)
but reviewers must also make judgements. It is crucial to make

(51)
but reviewers must also make judgements. It is crucial to make 
these important decisions explicit and to make them before seeing the data.The limit at which data become meaningless may differ depending on the question addressed. For example, in the situation of trialling a new oral drug for schizophrenia, clearly a loss of nearly 60 per cent of people at 6 weeks is clinically untenable. The reviewer may judge that the unfortunate clinician may lose up to 30 per cent of people by 6 weeks but that any greater loss would reﬂ  ect more than 
misfortune and render data of little use. In different circumstances, such as the acute care of very disturbed people in closed wards, the loss of even 10 per cent of participants could be seen as a threat to the value of the data presented.
(c) Intention-to-treat analysis
Interventions are not randomized in trials — it is the intention  to give

Interventions are not randomized in trials — it is the intention  to give 
treatments that is randomly allocated. Once people are lost to follow-up, the property of the randomization to distribute known and unknown confounding variables is under threat. The randomization has, in effect, been broken. The real threat of an introduction of selection bias has led to the phrase — once randomized, always analyze.
(3)
Once a limit to trial attrition has been set, reviewers must, before

(3)
Once a limit to trial attrition has been set, reviewers must, before 
seeing trial data, exercise more judgement in what outcome is to be attributed to those who were lost. It is impossible to avoid assump-tions, but these should be based on common sense if not evidence. For example, when presenting data for the outcome of ‘clinically improved’ , reviewers could assume, unless contrary information is provided in the trials, that those who left early did not have an important recovery. If good quality sources of information are available, this assumption can become more evidence-based. Perhaps an exemplary trial within a systematic review managed 100 per cent follow-up even on those who left the study early. If this trial found that 90 per cent of those who had not complied with the study protocol were not ‘clinically improved’ , it would provide a rationale for applying this ﬁ  gure to the other trials in 
the meta-analysis. Unless individual patient data are available,

the meta-analysis. Unless individual patient data are available, 
this process is impossible for continuous outcomes and only ‘completer’ data must be presented.
(d) Continuous data
Data on continuous outcomes are frequently skewed, with the mean not being the centre of the distribution. The statistics for meta-analysis are thought to be able to cope with some skew, but were formulated for parametric normally distributed data. Reviewers may wish to build in simple rules to avoid the potential pitfall of applying parametric tests to very skewed data. For exam-ple, in scale data where a mean endpoint score is provided with a standard deviation, when the latter is multiplied by 2 and is then greater than the mean, data could be stated to be too skewed to summate.
(52) This rule cannot be applied for scale data reporting 
change, rather than endpoint, scores.
A wide range of rating scales are available to measure outcomes

A wide range of rating scales are available to measure outcomes 
in mental health trials. These scales vary in quality and many are poorly validated. It is generally accepted that measuring instru-ments should have the properties of reliability (the extent to which a test effectively measures anything at all) and validity (the extent to which a test measures that which it is supposed to meas-ure). Before publication of an instrument, most scientiﬁ  c jour-
nals insist that both reliability and validity be demonstrated to the satisfaction of referees. Reviewers may well decide, as a mini-mum standard, to exclude data from unpublished rating scales.
(38)
(e) Individual patient data

(38)
Most mental health meta-analyses are of aggregate data from published reports. Other specialities have set a ‘gold standard’ for systematic reviews by acquiring, checking, and reanalyzing each person’s data from the original trialists.
(53) Collecting individual 
patient data allows reviewers to undertake time-to-event analyses and subgroup analyses, to ensure the quality of the randomization and data through detailed checking and correction of errors by communication with triallists, and ﬁ  nally to update follow-up 
information through patient record systems (such as mortality registers).
Limited empirical evidence exists for some of the advantages of

Limited empirical evidence exists for some of the advantages of 
individual patient data reviews over other types of review. The former does help to control publication bias, to ensure use of the intention-to-treat principle in the analysis, and to obtain a fuller picture of the effects of different treatments over time. Undertaking individual patient data reviews requires considerable additional skills, time, and effort on the part of the reviewers when compared to meta-analyses of published aggregate data.
(54)
Statistics
(a) Inappropriate meta-analyses
Systematic reviews may, or may not, contain meta-analyses. Where participants, interventions, or outcomes are clearly too different to summate, reviewers must resist the temptation to use powerful statistics on inappropriate data.
(41)
(b) Summary measures
Much has been written about the statistics for meta-analysis,(55)

(41)
but if their meaning is not conveyed to the user of the review, they are of little value. Summary measures such as odds ratios or relative risk are frequently employed for dichotomous outcomes and weighted and standard mean difference for continuous data. Where continuous data are presented from different scales measuring similar phenomena then standard mean difference is often calcu-lated and called the effect size. This estimate has statistical integrity, but is even more problematic to interpret clinically than weighted mean difference. In each of these summary measures, an individual trial contributes to the ﬁ  nal statistic, inversely proportional to the 
precision of its result.
Currently, in this new discipline, statistics for meta-analysis are 
powerful and evolving. In recent years, there has been a much bet-ter understanding of how best to summate data from cluster rand-

omized trials and crossover studies. T echniques for these types of analyses are now widely accessible. Further statistical ﬂ  exibility is 
available through use of generic inverse variance. This statistical 6.1.1 the evaluation of physical treatments

SECTION 6  treatment methods in psychiatry 1156
technique facilitates analyses of properly analyzed cross-over trials, 
cluster randomized trials and non-randomized studies, as well as outcome data that are ordinal, time-to-event or rates. Better meth-ods for managing non-parametric data can conﬁ  dently be expected 
in the next few years.
(41)
(c) Sensitivity analyses
This is where an analysis is used to determine how sensitive the results of the review are to changes in how it was undertaken. For example, the reviewers may state, again a priori , that they wish to 
compare the size of effect of industry-sponsored trials versus those undertaken independently of the manufacturer of the experimen-tal drug.
(7) The sensitivity of the final result to adding and

(7) The sensitivity of the final result to adding and 
subtracting sets of trials is then tested. Sensitivity analyses can be proposed on many variables, such as severity of illness, age of participant, means of diagnosis, subtype of intervention, and qual-ity of trial. This can easily lead to the problems of multiple testing, although for meta-analyses of published data the quality and extent of trial reporting severely restricts the numbers of sensitivity analyses that are possible.
(d) Heterogeneity
In systematic reviews heterogeneity refers to variability or differ-ences between studies’ estimates of effects and is a function of clinical and/or methodological diversity among the studies. Despite rigorous deﬁ  nition and application of inclusion criteria,

the trials eventually selected may not be homogeneous enough to summate. Heterogeneity should be considered, sought, and meas-ured, and, if present, investigated. Statistical tests of heterogeneity are used to assess whether the observed variability in study results (effect sizes) is greater than that expected to occur by chance. These tests, however, have low statistical power and careful inspection of results for outlying ﬁ  ndings is just as valuable. 
Recently, partly because it is more intuitive than previous meas-ures, the I
2 has become widely used. This quantiﬁ  es inconsistency 
across studies, moves the focus away from testing whether hetero-geneity is present to assessing whether the heterogeneity, that many argue is inevitable, will impact on the meta-analysis. A value greater than 50 per cent is often considered to indicate sub-stantial heterogeneity.
(41)

(41)
Heterogeneity can be caused by various factors, and its presence generates debate about differences in study design (methodological diversity) and differences between studies in key characteristics of the participants, interventions, or outcome measures (clinical diversity). Heterogeneity can be explored by undertaking subgroup analyses or employing meta-regression. In subgroup analyses, the results of one group of studies with a characteristic thought to be causing heterogeneity is compared to those of another group of trials without that characteristic. For example, trials of a new interpersonal therapy for depression may be heterogeneous. The reviewers may have stated, a priori , that the new therapy, targeted at 
young people, may not be effective for those over 30 years of age. Overall, although the trials may have heterogeneous results, if the two subgroups of studies involving people over and under the age 
of 30 have homogeneous results, it is feasible that the original

of 30 have homogeneous results, it is feasible that the original 
hypothesis of the reviews regarding age was correct. Meta-regres-sion, is an extension to subgroup analyses that allows the effect of variables, even several simultaneously, to be investigated. Again these variables should be pre-stated and this technique necessitates much high quality data to be meaningful. Even then, the regression is essentially an observational study with all the dangers of unex-
plained or residual confounding. In mental health reviews, investi-gation of heterogeneity often generates valuable debate, rather than providing deﬁ  nitive answers.
(e) Reporting bias
There are several ways to assess whether reporting (publication) 
bias (see above) is operating within a review. The reviews may use a funnel plot technique
(56) where the results of a trial are plotted

(56) where the results of a trial are plotted 
against its size. Large studies with any result, positive or negative, tend to be published. Small positive studies are also usually easily identiﬁ  ed, but it quickly becomes apparent if small ‘negative’ studies 
have not been found. This could be due to a variety of reasons, but one of which is a selective reporting of positive outcomes.
Sources of systematic reviews
Journals
Systematic reviews are increasingly seen in major journals. These can be identified by simple or comprehensive methodology-speciﬁ  c searches of bibliographic databases such as EMBASE, 
Medline, or PsycINFO. Examples of these searches can be readily identiﬁ  ed
(57) but need to be updated periodically to reﬂ  ect changes 
in notation or indexing. These search phrases would then be linked to a subject-speciﬁ  c phrase such as ‘depression’ or ‘cognitive therapy’ ,

in notation or indexing. These search phrases would then be linked to a subject-speciﬁ  c phrase such as ‘depression’ or ‘cognitive therapy’ , 
by the word ‘and’ to limit and focus the number of identiﬁ  ed 
citations.
DARE database
The Database of Abstracts of Reviews of Effectiveness (DARE) is a specialist database containing thousands of citations of system-atic reviews of health care. These reviews are assessed according to explicit criteria, and structured abstracts describing methodology and results, and commenting on quality and clinical implications, 
are also included.
Cochrane reviews
The Cochrane Database of Systematic Reviews is an electronic 
publication increasingly favoured by clinicians, researchers and those compiling guidelines. It contains the full text and data of reviews undertaken to the most rigorous systematic standards
(58)

(58)
and is updated quarterly. There is often a considerable lag time for traditional journal publication and this can result in the publi-cation of good-quality but misleading systematic reviews. For example, an important systematic review on the effects of family intervention for schizophrenia was published in August 1994.
(59)
Just 2 weeks later, the same authors re-summated relevant data in an electronic version and the results were much less favourable than had been previously reported.
(60) In the considerable period

(60) In the considerable period 
between completion of the paper version and its publication, less favourable trials appeared. Further updates of this review suggest that the trend is continuing. By using electronic publishing, the Cochrane Database of Systematic Reviews allows trends over time to be highlighted and reviews to be maintained.
The Cochrane Library is a collection of databases supplying 
high-quality evidence to inform all those interested in the evaluation of health care.
(45) It is published quarterly on CD-ROM 
and the Internet, and includes the Cochrane Database of Systematic Reviews, the source of many of the reviews quoted in this

1157
chapter, the DARE abstracts, and The Cochrane Controlled Trials 
Register.
Summary publications
There are now several periodically updated, systematically compiled, publications designed primarily for busy clinicians. For example, one such publication, Clinical Evidence,
(61) now has 
a comprehensive mental health subset, and is available in short or very short versions, providing clinical ‘bottom lines’ of relevant systematic reviews or randomized trials.
The Cochrane Handbook - http://www.cochrane-handbook.org/ contains 
up-to-date methodological details of systematic reviews and meta-analysis
Clinical Evidence - http://clinicalevidence.bmj.com/ceweb/index.jsp an 
on-line, regularly updated compendium of systematic evidence 
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6.1.2 The evaluation of

London.
6.1.2 The evaluation of 
psychological treatment
Psychotherapy continues to be a widely practised treatment for 
psychiatric disorders and other problems in living. Since publica-tion in 1952 of the well-known article by Hans Eysenck,
(1) in which 
he claimed that there was no evidence that psychotherapy was effective, there has been an accelerating literature concerned with methodologies for evaluating psychotherapy, as well as speciﬁ  c 
studies demonstrating the efﬁ  cacy, or lack thereof, of various psy-
chotherapies. In more recent years, pressures from the government agencies and insurance companies that bear much of the cost of mental health treatments have added to the call for accountability regarding psychotherapeutic treatment.
Despite a vast literature of over 1000 outcome studies of the

Despite a vast literature of over 1000 outcome studies of the 
effects of psychotherapy, questions remain about the role of psy-chotherapy as a treatment for mental disorders. Extensive meta-analytical reviews of the psychotherapy outcome literature provid-ed evidence that, generally speaking, psychotherapy appears to be 
efﬁ cacious.
(2) While encouraging, this information was not partic-
ularly useful. As with any medical problem or disorder, the relevant public health clinical question is whether a treatment is beneﬁ  cial 
for the presenting problem or psychiatric disorder for which help is sought. Along these lines, a number of efforts have been made at summarizing the results of the psychotherapy outcome literature in terms of what works for different disorders or problems.
(3, 4) For 
example, these efforts have arrived at conclusions such as ‘cognitive therapy is efﬁ  cacious in the treatment of major depressive disorder’ .

(3, 4) For 
The simplicity and clinical appeal of such conclusions, about 
which psychotherapy treatments work for which patient problems, belies a host of more complex issues regarding how one evaluates psychotherapy and makes a decision about whether treatment ‘works’ or not. Other treatments within psychiatry, such as phar-macotherapy, lend themselves to rather straightforward designs (namely placebo-controlled randomized clinical trials) that permit clear inferences about the efﬁ  cacy of a treatment approach. In con-
trast, research on psychotherapy as a verbal interchange between two or more participants does not have the luxury of such straight-forward pharmacotherapy research designs. Instead, psychotherapy outcome research is characterized by the use of a variety of research

designs and methods that, while often not without limitations to 
strong scientiﬁ  c inferences about treatment efﬁ  cacy, can provide 
incremental scientiﬁ  c advance in the understanding of the useful-
ness of psychotherapeutic treatments. The aim of the current chapter is to provide an overview of approaches to the evaluation

1159
of psychological treatments. We begin with a discussion of speciﬁ  c 
research designs employed in psychotherapy outcome research, with a discussion of some of the broad issues that currently guide the selection among these different experimental designs. This is followed by a selective review of assessment strategies for outcome evaluation, with discussion of examples of instruments.
Issues in planning research evaluating 
psychotherapy
A number of other sources provide a detailed discussion of issues 
involved in planning a study on psychotherapy, as well as explica-tion of various research designs. In particular, our presentation draws heavily from Kazdin,
(5) supplemented with writings that 
illustrate more recent trends in both design and methodology.
There are, of course, a wide range of decisions to be made in

There are, of course, a wide range of decisions to be made in 
designing an evaluation study of psychotherapy. These decisions affect the choice of patients, therapists, control groups, data ana-lytical strategies, etc. Table 6.1.2.1 presents a list of the types of questions that need to be asked in designing or evaluating a study of psychotherapy outcome. A discussion of some of the key meth-odological issues that cut across many of the questions raised in Table 6.1.2.1 follows.
Internal versus external validity
An initial important decision in planning an evaluation of psycho-therapy outcome, or any intervention, is the relative emphasis on internal versus external validity of the inferences from the investi-gation. Internal validity refers to the extent to which inferences can be attributed to the intervention per se , as opposed to other factors.

In order to maximize internal validity, the investigator attempts to control as many of the extraneous factors as possible through a variety of procedures including, among others, random assign-ment, the use of control groups, assessing subjects in the same ways and at the same point in time, and careful selection of a relatively homogeneous subject sample. With as many factors as possible held constant across treatment groups except for the nature of the intervention, an outcome difference detected between the experi-mental and control group(s) can be attributed to the intervention, 
rather than other factors.
External validity, in contrast, refers to the extent to which the 
results of a study can be generalized to other subjects, settings, treatment durations, and treatment providers other than those used within the speciﬁ  c study. In regard to the evaluation of psy-

chotherapy outcomes, external validity is often invoked to raise the question of whether study results pertain to the ‘real world’ in which psychotherapy is practiced—the diverse set of patients, ther-apists, and settings occurring in the community that may be quite different from the conditions of an investigation conducted in a research setting.
Clearly, both internal and external validity are important, but 
it is difﬁ  cult to maximize each within the context of the same

it is difﬁ  cult to maximize each within the context of the same 
study. Studies of homogeneous patient samples, for example, may have high internal validity, but generalize poorly to the mix of heterogeneous patients seen in clinical practice. The relative merits of studies with high internal versus external validity have been a source of ongoing debate among psychotherapy outcome researchers.Different research designs are more or less appropriate depend-
ing upon the scientiﬁ  c question of interest. For example, the pro-

cess of developing and testing new treatments generally proceeds stepwise, beginning with individual case reports and then progress-ing to an ‘open-label’ (a term derived from pharmacotherapy research) trial involving the application of a single treatment to a relatively small group of patients. Following an open-label trial, a promising treatment would then be tested within the context of a controlled, efﬁ  cacy trial. In this efﬁ  cacy trial, the treatment 
would be tested under ideal circumstances (for instance, by highly trained clinicians). If an effect is found in the controlled efﬁ  cacy 
trial, a controlled, effectiveness trial is the next step. In this effec-tiveness trial, the treatment would now be tested under more ‘real world’ conditions. This line of research is oriented towards understanding whether the treatment per se  is responsible for

change (efﬁ  cacy trial) and whether the effect generalizes (effective-
ness trial).
Naturalistic studies represent an alternative type of effectiveness 
trial in which the scientiﬁ  c question is usually not a focus of type 
of treatment. Instead, such studies might examine the relationship of patient characteristics, therapist factors, or length (dose) of treatment to outcome.
Selection criteria for psychotherapy 
outcome studies
The choice of selection criteria for a psychotherapy outcome study 
depends, of course, on the nature of the research q uestion to be 
asked. From a public health perspective, samples are usually chosen based upon the presence of a discrete disorder or problem that has signiﬁ  cance to society. The selection of the target disorder, however, is

only the beginning of the selection process. For studies of DSM Axis I non-psychotic disorders, it is typical that other major psychotic disorders such as schizophrenia and bipolar disorder are excluded from the study. However, there is wide variability across research studies in the extent to which other Axis I and Axis II disorders are included in a study or not.
This aspect of selection criteria relates primarily to the internal 
versus external validity distinction discussed above. Studies that emphasize internal validity will probably exclude many comorbid 
diagnoses, while studies that maximize external validity will tend to 
be more inclusive. As the comorbidities among Axis I diagnoses can be high, the impact on the nature of the patient sample selected can be considerable.
Naturalistic studies that focus on psychotherapy per se , rather

Naturalistic studies that focus on psychotherapy per se , rather 
than public health concerns, are oriented towards external validity and typically do not have restrictive selection criteria. For these studies, the question is ‘how effective is psychotherapy for the types of patients that end up in psychotherapeutic treatment in the com-munity?’ Thus, few, if any, selection criteria are speciﬁ  ed.
One particular selection problem that affects any type of psycho-
therapy outcome study is whether or not patients currently treated with psychotropic medication are included in the evaluation study. Once again, from the point of view of internal validity—attempting to attribute the treatment outcome to the psychotherapy treatment per se —patients on concurrent medication treatment

are usually excluded. In contrast, external validity concerns would lead to the inclusion of patients on medications, since increasing numbers of patients in the community with anxiety and affective 6.1.2 the evaluation of psychological treatment

SECTION 6  treatment methods in psychiatry 1160
Table 6.1.2.1 Selected questions to raise in planning a study of psychotherapy
Sample characteristics
1 Who are the subjects and how many of them are there in this study?
2 Why was this sample selected in light of the research goals?
3 How was this sample obtained, recruited, and selected?4 What are the subject and demographic characteristics of the sample (e.g. sex, age, ethnicity, race, socio-economic status)?
5 What, if any, inclusion and exclusion criteria were invoked (i.e. selection rules to obtain participants)?
6 How many of those subjects eligible or recruited actually were selected and participated in the study?7 With regard to clinical dysfunction or subject and demographic characteristics, is this a relatively homogeneous or heterogen eous sample?
Design
1 How were subjects assigned to groups or conditions?

Design
2 How many groups were included in the design?3 How are the groups similar and different in how they are treated in the study?
4 Why are these groups critical for addressing the questions of interest?
Procedures
1 Where was the study conducted (setting)?
2 What measures, materials, equipment, and/or apparatus were used in the study?
3 What is the chronological sequence of events to which subjects were exposed?4 What intervals elapsed between different aspects of the study (assessment, treatment, follow-up)?
5 What variation in administration of conditions emerged over the course of the study that may introduce variation within and b etween conditions?
6 What procedural checks were completed to avert potential sources of bias in implementing the manipulation and assessment of d ependent measures?
7 What checks were made to ensure that the conditions were carried out as intended?

8 What other information does the reader need to know to understand how subjects were treated and what conditions were provided ?
Therapists
1 Who are the therapists, and why are these individuals selected?2 Can the inﬂ  uence of the therapist be evaluated in the design as a ‘factor’ (as in a factorial design) or can therapist effor ts be evaluated within a condition?
3 Are the therapists adequately trained? By what criteria?
4 Can the quantity and quality of their training and implementation of treatment be measured?
Treatment
1 What characteristics of the clinical problem or cases make this particular treatment a reasonable approach?
2 Does the version of treatment represent the treatment as it is usually carried out?3 Does the investigation provide a strong test of treatment? On what basis has one decided that this is a strong test?

4 Has treatment been speciﬁ  ed in manual form or have explicit guidelines been provided?
5 Has the treatment been carried out as intended? (Integrity is examined during the study but evaluated after it is completed.)6 Can the degree of adherence of therapists to the treatment manual be codiﬁ  ed?
7 What deﬁ  nes a completed case (e.g. completion of so many sessions)?
1 If speciﬁ  c processes in the clients or their interpersonal environment are hypothesized to change with treatment, are these to be assessed?
2 If therapy is having the intended effect on these processes, how would performance be evident on the measure? How would group s differ on this measure?
3 Are there additional processes in therapy that are essential or facilitative to this treatment, and are these being assessed?
4 Does the outcome assessment battery include a diverse range of measures to reﬂ  ect different perspectives, methods, and domai ns of functioning?

5 What data can be brought to bear regarding pertinent types of reliability and validity for these measures?6 Are treatment effects evident in measures of daily functioning (e.g. work, social activities)?
7 Are outcomes being assessed at different times after treatment?
Data evaluation
 1 What are the primary measures and data upon which the predictions depend?
 2 What statistical analyses are to be used and how speciﬁ  cally do these address the original hypotheses and purposes?
 3 Are the assumptions of the data analyses met? 4 What is the likely effect size that will be found based on other treatment studies or meta-analyses?
 5 Given the likely effect size, how large a sample is needed to provide a strong powerful test of treatment (e.g. power ≥ 0.80 )?

5 Given the likely effect size, how large a sample is needed to provide a strong powerful test of treatment (e.g. power ≥ 0.80 )?
 6 Are there subdivisions of the sample that will be made to reduce the power of tests of interest to the investigator? 7 What is the likely rate of attrition over the course of treatment, and post-treatment and follow-up assessments?
 8 With the anticipated loss of cases, is the test likely to be sufﬁ  ciently powerful to demonstrate differences between groups  if all cases complete treatment?
 9 If multiple tests are used, what means are provided to control error rates?10 Prior to the experimental conditions, were groups similar on variables that might otherwise explain the results (e.g. diagno sis, age)?
11 Are data missing due to incomplete measures (not ﬁ  lled out completely by the subject(s) or loss of subjects)? If so, how ar e these handled in the data analyses?

12 Will the clinical signiﬁ  cance of client improvement be evaluated and if so by what method(s)?
13 Are there ancillary analyses that might further inform the primary analyses or exploratory analyses that might stimulate fur ther work?
Reproduced with permission from A. Kazdin. Methodology, design and evaluation in psychotherapy research. In Handbook of Psychotherapy and Behavior Change  (eds. A.E. Bergin and S.L. 
Garﬁ  eld), pp. 19–71. Copyright 1994, John Wiley & Sons, Inc.

1161
disorders are receiving psychotropic medications for their prob-
lems. Often, a compromise is struck: patients on medications are eligible for the psychotherapy study as long as they (and their pre-scribing doctor) agree to maintain a stable dosage of the medication for the duration of the psychotherapy study.
Treatment standardization
Psychotherapy efﬁ  cacy research, like pharmacotherapy research, 
requires that the treatment be standardized. Such standardization serves two related purposes. First, from a clinical point of view, it is necessary that the treatment be clearly specified, so that any conclusions about differential treatment efﬁ  cacy can be translated

into clear treatment recommendations. From a research point of view, treatment standardization allows studies to be replicated. In addition, by making the delivery of a treatment more standard-ized, differences between therapists and the statistical problems that result from the non-independence that ‘therapist effects’ introduce can be avoided.
(6)
Standardization of pharmacological interventions is relatively

(6)
Standardization of pharmacological interventions is relatively 
straightforward—a per-day dosage (or range of dosages) is set in advance. But for psychotherapy, how can something so complex as patient–therapist dialogue be standardized? The central ingredient in standardization of a psychosocial treatment is a treatment manual. A psychotherapy manual describes the treatment in detail, with case examples and instruments for psychotherapists. Some treatment manuals, particularly those coming from a cognitive behavioural perspective, present a highly systematized step-by-step programme which therapists follow over the course of therapy. The relative success of treatment manuals in standardizing psycho-therapy has been supported by a meta-analysis,
(7) which document-

ed that studies employing treatment manuals had fewer outcome differences between therapists compared with studies that did not employ treatment manuals. Thus, when a treatment manual is used, therapists appear to produce relatively more uniform outcomes. In contrast, when no treatment manual is used, therapists differ considerably in their typical outcomes with patients; suggesting that different therapists are likely to be conducting sessions in discrepant ways, with some therapists producing more favourable outcomes and other therapists producing less favourable outcomes.
Treatment standardization, however, does not simply translate 
to the use of a treatment manual. A variety of steps are needed to ensure that therapists are delivering the intended treatment (Table 6.1.2.2), including: the careful selection of therapists; train-
ing of therapists in the intended modality using a treatment manu-
al; certiﬁ  cation of therapists based upon their adherence to the

al; certiﬁ  cation of therapists based upon their adherence to the 
treatment model during training; and continuing adherence and competence monitoring of therapists during a clinical trial.
Concerns have been raised about the ‘treatment manual’ concept 
applied to less directive treatments such as psychodynamic therapy. The belief is that session-by-session manuals would remove the essence of good psychotherapy, and good dynamic therapy in particular, by making treatment artiﬁ  cially rigid and taking away 
the necessary clinical ﬂ  exibility and creativity. Psychodynamic 
treatment manuals, however, are perhaps better described as ‘guides’ , which specify the principles of treatment but do not overly constrain the necessary clinical flexibility and creativity. The ﬂ exibility of treatment is fully retained through the principle of tailoring the treatment intervention to the speciﬁ  c idiosyncratic

issues that are salient for each patient. The actual learning of the practice of treatment is accomplished through supervision in the application of the treatment manual. Because dynamic treatment manuals are less like ‘cookbooks’ , there may be a greater reliance on the supervision process compared with perhaps more straight-forward behavioural treatments.
Research designs
Unlike pharmacological research where a single form of research design (placebo-controlled study) dominates the literature, psy-chotherapy researchers have employed a host of different research designs to understand the effects of psychotherapy. Some of the more common designs are listed in Table 6.1.2.3 and are explicated in the next section.
Single-case designs

Clinical evaluation of the effects of psychotherapy dates back to Freud’s descriptions of individual cases in treatment. However, methods to systematically examine the effects of interventions with individual patients were developed by behaviour therapists.
(8)
These single-case experiments rely on comparing patient responses to differing experimental conditions over time. Typically, such sin-gle-case studies begin with an extended baseline period where patient behaviours or symptoms are recorded without any inter-vention. Then, different intervention phases are introduced, usually followed by more baseline (no intervention) assessment phases.
While experimental, single-case designs lend themselves well to

While experimental, single-case designs lend themselves well to 
the investigation of behavioural treatments that include a focus on immediate overt behaviour, such designs have rarely been employed with other verbal psychotherapies that emphasize longer term processes such as patient psychological growth and functioning. The generalizability of ﬁ  ndings from single-case research is another 
limitation to this form of research.Table 6.1.2.2 Steps involved in the standardization of 
psychotherapy for outcome research
Selection of therapists
Training of therapists using a treatment manualCertiﬁ  cation of therapists based upon adherence to the treatment modelContinued assessment of therapist adherence and competence during a 
 clinical trial6.1.2 the evaluation of psychological treatment
Table 6.1.2.3  Common research designs for the evaluation of 

clinical trial6.1.2 the evaluation of psychological treatment
Randomized controlled trials with non-speciﬁ  c or psychological ‘placebo’ controlComparative designsDismantling or additive designsComparisons with medication and pill placebosNaturalistic designs

SECTION 6  treatment methods in psychiatry 1162
Randomized controlled trials
Random assignment of subjects to treatment and control condi-
tions is generally viewed as the preferred method of evaluating the effects of interventions in psychiatry, and in medicine in general. However, perhaps the single most vexing problem in research of psychotherapy outcome is the design of control groups. In phar-macotherapy research, a pill placebo (with ‘double blinding’ , i.e. the patient and the doctor are unaware of treatment assignment) serves to control for all elements of treatment except for the chemical ingredient of interest. Thus, the overall effects of treatment are the sum of the speciﬁ  c effect of the chemical agent plus the effects of 
‘extraneous’ or non-speciﬁ  c factors such as patient expectancy,

‘extraneous’ or non-speciﬁ  c factors such as patient expectancy, 
hope, and aspects of the doctor-patient relationship. With psycho-therapeutic treatments, it is less clear which aspects of treatment are speciﬁ  c and which are non-speciﬁ  c. Furthermore, designing 
a credible control treatment that contains only the non-speciﬁ  c 
elements of the treatment package is inherently difﬁ  cult.
(a) Types of control groups
A variety of types of control conditions have been implemented in 
psychotherapy efﬁ  cacy studies. One common form of control

psychotherapy efﬁ  cacy studies. One common form of control 
group is the ‘waiting-list’ control. Patients are randomly assigned to either the experimental group or to delayed treatment. While such a control condition appears to control for the passage of time (i.e. patients generally improve over time even without treatment), assignment to a waiting-list control condition is likely to immedi-ately change patient hope and expectations about relief of their problem. Patients in the waiting-list condition will not expect to improve until they actually receive treatment, while patients assigned to the experimental condition will likely be more hopeful about change. Thus, the treatment and control conditions are not balanced with regard to expectancy or other non-speciﬁ  c fac-

tors such as regular meetings with a competent caring professional. The potential superiority of the experimental condition over the 
control condition cannot be attributed to the hypothesized active 
ingredients in the experimental condition. Nevertheless, such wait-ing-list controls can serve as a useful initial step in evaluating a treatment.
A scientiﬁ  cally stronger type of control group for psychotherapy 
evaluation studies is one that involves regular meetings with a psy-chotherapist, but does not contain certain important hypothesized active elements. Some forms of supportive psychotherapy have been used as a control group in this regard. For example, in evalu-ating the efﬁ  cacy of cognitive behavioural therapy for posttrau-
matic stress reactions, a supportive therapy control condition has been successfully used.
(9) With some psychotherapy treatments,

(9) With some psychotherapy treatments, 
however, the supportive elements are an important part of the overall treatment model and are hypothesized to be curative in their own right. In this case, a supportive psychotherapy control condition is not appropriate for evaluating the efﬁ  cacy of the over-
all package. In fact, sometimes supportive therapy has been found to be superior to other therapies.
(10)
Comparative designs
An alternative to attempting to create an adequate psychological ‘placebo’ control is to only compare active treatments rather than comparing active treatments to ‘placebo’ control groups. However, rather than solve the problem of how to evaluate the efﬁ  cacy of 
a psychotherapeutic intervention, comparative designs simply change the scientiﬁ  c question from ‘Is this treatment efﬁ  cacious?’

a psychotherapeutic intervention, comparative designs simply change the scientiﬁ  c question from ‘Is this treatment efﬁ  cacious?’ 
to ‘Which treatment works best?’ Comparative designs are gener-ally only informative if one active treatment proves to be more effective than another. If, as is commonly the case in psychotherapy studies, both active treatments produce equivalent results, the investigator is left not knowing whether both treatments are effec-tive, or whether both treatments are non-effective (beyond the effects of non-speciﬁ  c elements).
Dismantling designs
Dismantling designs are an alternative to psychological placebos, 
waiting lists, or comparative designs. In a dismantling design, the full clinical treatment package is compared with the full package minus one element in order to establish which elements are neces-sary and sufﬁ  cient for change. Variations on this theme include

‘additive’ or constructive designs that examine whether adding a new element enhances the efﬁ  cacy of a treatment package.
As an example, dismantling designs have been usefully applied in 
the evaluation of the behavioural treatment of obsessive-compulsive disorder. The full treatment package involving exposure and response prevention techniques has been compared with each of the individual components of the package.
(11) Patients were 
randomly assigned to either the full exposure and response preven-tion package, exposure alone, or response prevention alone. Those receiving the full package improved signiﬁ  cantly more than did 
the patients in either of the control treatments. At follow-up assess-ments, 80 per cent of patients receiving the full package remained improved at follow-up, whereas only 27 per cent of those in the single components groups remained ‘improved’ .
The advantage of dismantling strategies in psychotherapy

The advantage of dismantling strategies in psychotherapy 
research is clear. Causal statements about differences in improve-ment between treatment conditions can be made, since all factors (including non-speciﬁ  c elements) except one are held constant, 
and the problems involved in other types of control groups are avoided. These designs, in general, should probably be used more 
often than they are. Some psychotherapies, however, may not easily 
lend themselves to such dismantling strategies. Moreover, it may be premature to attempt to dismantle a treatment package when questions about the efﬁ  cacy of the whole package need to be 
resolved ﬁ  rst.
Comparisons with medication
One type of design for the evaluation of psychotherapy that has

One type of design for the evaluation of psychotherapy that has 
increased in importance consists of comparisons to medication treatments. An example of this type of study is a recent investiga-tion comparing cognitive therapy, medication (paroxetine), and pill placebo in the treatment of moderate to severe major depres-sive disorder.
(12) The rationale for this design is that the medication 
group provides the standard reference condition with established efﬁ cacy. The pill-placebo group allows for establishing that the par-
ticular sample in the study showed the typical medication-placebo difference that would be expected (in other words, the sample was not unusual), and controls for some of the non-speciﬁ  c effects of

the psychotherapy (for example, regular visits to a professional, positive expectancies for change). While the pill placebo is clearly not a perfect control condition for psychotherapy, it serves as a practical function—i.e. if a speciﬁ  c psychotherapy is not better 
than a pill placebo, should the psychotherapy be pursued as a treat-ment option?

1163
Attribute by treatment interactions
An emerging emphasis in psychotherapy outcome research is 
the investigation of attribute by treatment interactions. Partly inﬂ uenced by the common ﬁ  nding of no differences between 
psychotherapies, as well as the desire to make more speciﬁ  c clinical 
recommendations, investigators have hypothesized that certain matches of client characteristics and treatment modalities produce superior outcomes. One initial problem with pursuing potential matches of patient characteristics with the type of treatment is that there are a large number of potential variables (for instance, various combinations of diagnosis, therapist, treatment, patient’s problem, setting).
The investigation of patient-treatment matches has intuitive 
clinical appeal, as most therapists believe that some patients seem to ‘ﬁ t’ a form of treatment better than others. Research on patient-
treatment matching, however, is inherently difﬁ  cult, particularly

treatment matching, however, is inherently difﬁ  cult, particularly 
because large sample sizes are generally needed to adequately test interaction effects. Two of the largest randomized clinical trials ever performed with psychotherapeutic treatments have failed to ﬁ nd much support for speciﬁ  ed patient-treatment interactions.
(13,14)
Thus, it remains to be seen whether aptitude by treatment-
interaction designs will provide useful information about psycho-therapy outcome.
Naturalistic studies
Naturalistic designs are used to examine issues such as the effectiveness of treatments in real-world setting with the types of patients that typically seek treatment. For example, the effectiveness of cognitive behavioural therapy for panic disorder and agoraphobia has been examined in a naturalistic study.
(15)

(15)
The authors report that outcomes were better for patients receiving naturalistic cognitive behaviour therapy, compared to a non-randomized wait-list control group. However, the overall outcomes for cognitive behavioural therapy were not as robust as previously seen in controlled clinical trials. While this form of naturalistic study has several advantages, including the fact that the data are drawn from actual clinical services in the real world, such data do not add to an understanding of which forms of psychotherapy work and which do not, and they do not provide strong causal statements. Hypotheses generated from naturalistic studies can inform the planning of experiments that can make stronger statements about causality. In addition, naturalistic studies provide useful descriptive information about the service 
delivery system.
Strategies for assessing psychotherapy outcome
Once a particular experimental design has been decided upon,

Once a particular experimental design has been decided upon, 
the next crucial question in evaluating psychotherapy pertains to the selection of instruments for the study. Instruments include those needed to adequately select a patient population, such as measures of psychiatric diagnoses and initial symptomatology. Therapeutic change is often evaluated on a broad range of measures including dimensional measures of symptoms, personal-ity, self-esteem, quality of life, and functioning in a variety of areas (for example, social and occupational functioning). In addi-tion, the impact of treatment on speciﬁ  c theoretical constructs 
(mediators) can be examined. Discussion of each of these domains follows.Patient selection
Because the identiﬁ  cation of effective therapies for speciﬁ  c disor-

ders is an important research priority from a public health point of view, an accurate and thorough assessment of these disorders is central to the evaluation process. The most widely used instrument for assessing the major DSM-IV Axis I diagnoses in research settings is the Structured Clinical Interview for DSM-IV .
(16) The 
format of this semi-structured interview, with questions grouped by criteria and by diagnosis, allows an experienced clinical evalua-tor to assign diagnosis as the interview progresses. It is most commonly used to select subjects according to study inclusion or exclusion criteria or to characterize a study population. It can also be used to document change in diagnostic status post-treatment or over the course of a longitudinal study.
(b) Symptom measures

Whereas categorical measures are critical for the selection of a rela-tively homogeneous patient sample at intake, the evaluation of patient improvement requires the measurement of symptoms and functioning on a continuum. These continuous measures of the amount, timing, and nature of change are typically the primary outcomes of intervention studies. They include ratings of a single construct representing a core feature of the disorder, scales which cover the range of symptoms present in a general diagnostic cate-gory (e.g. rating scales of ‘depression’ or ‘anxiety’), and measures that cut across many diagnoses and are indicative of overall psychopathology or symptomatology. At each of these levels of assessment, one can ﬁ  nd both clinician-rated and self-report tools; 
for practical reasons, the self-report method predominates.
Measures of therapeutic change
(a) Dimensional assessment of core symptoms

In general, the more circumscribed and behavioural the problem, the simpler the assessment method. For some disorders, investiga-tors have found that single-item measures of target symptoms sufﬁ ce. For example, treatment studies of panic disorder and buli-
mia rely on self-reporting the number of ‘episodes’ that occur in a well-deﬁ  ned interval, such as the past week or the past month. 
Daily diaries are often used to facilitate recall and to enhance accuracy. Obsessive-compulsive symptoms can be assessed by Likert-type ratings of the severity of compulsions and obsessions, and the improvement of speciﬁ  c phobias by ratings of fear and 
avoidance. Severity ratings can be completed by both the patient 
and an independent evaluator.
For most disorders, core symptom measures of greater psycho-

metric sophistication are needed to supplement simpler methods. 
The Penn State Worry Questionnaire,
(17) for example, assesses 
the central feature of generalized anxiety disorder, and the Y ale-Brown Obsessive-Compulsive Scale
(18) measures the various symp-
toms that occur with obsessive compulsive disorder. In eating disorder research, the self-report EDI-2
(19) and the Eating Disorder 
Examination(20) are commonly used.
In depression research, the Inventory of Depressive 
Symptomatology(21) is the result of efforts to develop a continuous 
measure of the nine DSM symptoms for major depressive episode. Other widely used scales include the interview-based Hamilton Rating Scale for Depression
(22) and the self-report Beck Depression 6.1.2 the evaluation of psychological treatment

SECTION 6  treatment methods in psychiatry 1164
Inventory,(23) although these instruments do not map directly on 
to DSM criteria. The severity of speciﬁ  c manic symptoms can be 
assessed with either the Bech-Rafaelsen Mania Scale(24) or the 
Y oung Mania Rating Scale.(25)
(b) General measures of anxiety, depression, and other symptoms
The Hamilton Rating Scale for Depression and the Beck Depression Inventory are often administered concurrently to provide clinician and patient perspectives on the level of depression, and are used both as primary outcome measures in studies of depression, and as secondary measures in treatment studies of other disorders. Because of the comorbidity of Axis I disorders in general, and the interrelatedness of anxiety and depression in particular, it is useful to include assessments of both depression and anxiety. General measures of anxiety include the Hamilton Anxiety Rating Scale
(26)
and the Beck Anxiety Inventory.(27) These general measures are

(26)
and the Beck Anxiety Inventory.(27) These general measures are 
used with a variety of diagnostic groups, but it is important to remember that they have varying relevance to different disorders within a given diagnostic group. For example, a score on the Beck Anxiety Inventory might be a good index of the severity of the generalized anxiety disorder, but be less informative about speciﬁ  c 
phobias or obsessive-compulsive behaviour.
(i) Psychotic symptoms
In psychological treatment studies of severe depression, mania, and psychotic disorders, it is often necessary to assess the level of psychot-ic symptomatology. The Brief Psychiatric Rating Scale
(28) is recom-
mended for this purpose. It has items covering ﬁ  ve symptom clusters:

mended for this purpose. It has items covering ﬁ  ve symptom clusters: 
thinking disturbance, anxious depression, withdrawal/retardation, hostile/suspiciousness, and agitation/excitement. As with other clini-cian-rated scales, it should be administered by an experienced clini-cian who has received standardized training on this instrument.
(ii) Substance use problems
Because of the frequent comorbidity of substance use problems with other Axis I disorders, it is important to evaluate the level of drug and alcohol use when screening patients for study enrollment or when characterizing a sample. The substance use modules of the DSM-IV Structured Clinical Interview are frequently used for this purpose. The Addiction Severity Index
(29) has the advantage of providing

(29) has the advantage of providing 
more comprehensive and detailed information on problem areas associated with abuse, and yields scores that can be compared across patients, and from the beginning to the end of treatment. Because it is a rather time-consuming interview, it is recommended only in instances when the rates of substance use and related problems are expected to be high and their measurement is a research priority.
(c)  Measure of global psychological functioning/
psychopathology
The rationale for using measures that cover a broad range of

The rationale for using measures that cover a broad range of 
psychopathology is that they characterize the sample in terms of associated symptoms (i.e. symptoms other than those of primary interest) and provide a global measure of subjective distress. They have also proved to be quite useful in detecting treatment-related changes in evaluations of diverse psychotherapies. A popular self-report measure of general psychopathology is the SCL-90-R (and its abbreviated version, the Brief Symptom Inventory).
(30) The 
SCL-90-R is a 90-item scale; the Brief Symptom Inventory is com-posed of 53 items. Both yield nine symptom dimensions and three global indices of distress. Because correlations between the two instruments are very high, it is recommended that the latter be used when time is an issue or when this measure is included as part 
of a larger core battery of assessment.
(d) Measures of self

Many psychotherapies explicitly attempt to improve self-esteem, self-concept, and self-conﬁ  dence, and therefore it is relevant to 
examine the extent to which treatment successfully impacts on these domains. One of the oldest and most widely used measures of self-esteem is the Rosenberg Self-Esteem Scale,
(31) an easily admin-
istered 10-item Likert-type scale yielding a uni-dimensional indicator of global self-esteem. More recent work in this area aims to distinguish other self-related constructs (such as self-concept) from self-esteem, develop more theoretically based multifactorial models, and improve upon the psychometrics of earlier measures. Some resulting scales, such as the Beck Self-Concept T est
(32) or the 
Selves Questionnaire,(33) are appropriate for patients with a fairly 
wide range of psychiatric diagnoses.
(e) Personality assessment

(32) or the 
Personality variables typically appear in evaluations of psychologi-cal treatment as either primary outcomes (as in the study of psycho-therapy for personality pathology), or as prognostic indicators in studies of other Axis I disorders. They might also be included as part of a larger effort to thoroughly describe the patient sample. There are two ways to approach the evaluation of personality within these contexts: determination of the presence or absence of a DSM per-sonality disorder, and dimensional ratings of personality features.
(i) Categorical: DSM-IV Axis II
Treatments that target speciﬁ  c personality disorders tend to rely on 
the ﬁ  rst approach to assessment, namely the use of interviewer-
administered instruments which assess criteria for the 10 speciﬁ  c

administered instruments which assess criteria for the 10 speciﬁ  c 
personality disorders listed in the DSM-IV . The Structured Clinical Interview for DSM-IV Axis II
(34) was designed for this purpose. 
A positive feature of this assessment is its efﬁ  ciency in eliciting the 
information required to assign Axis II diagnoses, especially when used in conjunction with the self-report Personality Disorder Questionnaire.
(ii) Dimensional
Dimensional methods of assessing personality arise from either theoretical or factor-analytical models of the essential elements of personality structure. The Five Factor Model
(35) proposes that 
personality, in both patient and non-patient samples, can be mea-sured along ﬁ  ve dimensions: neuroticism, extraversion, openness 
to experience, agreeable, and conscientiousness. Extremes of these traits deﬁ  ne personality pathology. This model and several instru-

ments used to generate scores on these factors, including the self-report NEO Personality Inventory and NEO-PI-R
(36) and 
a semistructured interview (the Structured Interview of the Five-Factor Model of Personality
(37)), have received considerable 
empirical support in both clinical and non-clinical samples.
Another dimensional measure of personality is the SWAP-200.(38)
This instrument consists of a set of 200 personality-descriptive statements designed to be used by a clinician who knows a given patient well. The clinician arranges the 200 statements into eight categories, from those that are not descriptive to those that are highly descriptive of the patient. These scores are then used to generate both individualized, ideographic case descriptions as well as dimensional scores for the 10 personality disorders included in DSM–IV .

1165
The categorical and dimensional methods are not entirely 
mutually exclusive and both are valuable in ongoing research into the phenomenology, aetiology, correlates, and treatment of person-ality disorder.
(f) Measures of functioning and quality of life
In recent years, the deﬁ  nition of mental health has been broadened 
to encompass its more positive, and somewhat paradoxically, its more negative aspects. Mental health is now viewed as more than the absence of illness, but the illness itself is increasingly seen as chronic and quite disabling. This has prompted investigators to turn their attention to outcomes other than symptom change—to evaluate fully the effectiveness of a psychotherapeutic intervention means to document its broad effect on a number of relevant domains including social/interpersonal functioning, work func-tioning, and quality of life.
(i) Overall functioning

Incorporated into the DSM system as a separate axis (Axis V), the Global Assessment of Functioning scale
(39) (GAF) is the most 
widely used measure of psychosocial impairment. Clinicians rate on a scale of 1 to 100 the current level of functioning, or if desired, the highest or lowest level of functioning within some designated time period. General well being and functioning are also assessed with scales that have been developed for the routine outcome assessment in clinical practice, rather than for efﬁ cacy trials. An example is the OQ-45,
(40) a self-report measure 
consisting of three subscales representing broad content areas: (1) symptom distress, (2) interpersonal relations, and (3) social role (dissatisfaction and distress in tasks related to work, family roles, and leisure life).
(ii) Social and occupational functioning
The assessment of role performance has a fairly long history in psychotherapy research. The Social Adjustment Scale (SAS)
(41) was

(41) was 
developed to document the level in functioning in six areas: work as worker, ‘housewife’ , or student; social activities; relationship with family; relationship with spouse; parental responsibilities; member of a family unit. There is much documentation of its psychometric properties and clinical utility, and it has been used with a wide range of adult outpatients. A unique feature of the Longitudinal Interval Follow-up Evaluation (LIFE)
(42) is that it was designed 
to collect information on psychosocial functioning (as well as on diagnosis and symptoms) over longer periods of time. In the hands of trained evaluators, it is a structured interview that has been shown to have good reliability.
The concern among both scientists and health-care managers

The concern among both scientists and health-care managers 
about the cost-effectiveness of speciﬁ  c treatments has generated 
interest in more comprehensive assessments of work functioning and productivity. Endicott and Nee developed the Endicott Work Productivity Scale,
(43) a self-report instrument containing 25 items 
designed to be sensitive to more subtle differences among patients in work attitudes and behaviour.
Two self-report instruments measuring interpersonal difﬁ  culties 
have been used in studies of psychotherapy: The Inventory of Interpersonal Problems
(44) and the Dyadic Adjustment Scale.(45)
The Inventory of Interpersonal Problems is a 127-item self-report measure with high internal consistency and test-retest reliability of each of the six subscales: assertive, social, intimate, submissive, responsible, and controlling. The Dyadic Adjustment Scale is a 32-item scale designed to assess the severity of relationship discord

in married and unmarried cohabiting couples, with higher scores indicating better adjustment. Responses on the Dyadic Adjustment Scale discriminate between distressed and non-distressed couples 
and yield a total score based on the factors of dyadic consensus, 
dyadic cohesion, dyadic satisfaction, and affectional expression.
(iii) Quality of life
The most promising of the quality-of-life measures for mental health outcome research are those based on a broad deﬁ  nition of 
quality of life—covering role functioning and social-material con-ditions as well as life satisfaction or well being—and which can be applied across disorders and across treatments. However, more widespread use and testing of quality-of-life instruments is needed to establish their utility and to help resolve a number of important measurement issues, including the value of more ‘objective’ indices of quality of life and the relationship between symptoms and quality-of-life judgments.

(g) Utilization of treatment services
The impact of a treatment on usage of other health-related services is a factor to be considered in determining the cost-effectiveness of that treatment. One broad instrument designed to assess changes in service usage over the course of treatment is the Treatment Services Review.
(46) This is a 5-minute interview that documents 
the number and types of treatment services received during reha-bilitation from substance abuse, but it also can be adapted for use with other clinical populations.
(h) Theory-based measures

Evaluation of the hypothesized important psychological constructs of a particular psychotherapy can serve as outcome measures in their own right or as mediators of change in symptoms and functioning. For example, the cognitive model of depression holds that distorted cognitions about the self and world are responsible for generating and maintaining negative emotions. Measures of depressogenic cognitions are therefore included as outcomes and mediators of symptom change in studies of cognitive therapy for depression. The Hopelessness Scale
(47) is a 20-item self-report scale 
that assesses the hopelessness and pessimism associated with suicidal ideation and intent. The Dysfunctional Attitudes Scale
(48)

(48)
is a 40-item index of general attitudes and beliefs hypothesized by Beck and colleagues to underlie a propensity for depressive thinking, whereas the Automatic Thoughts Questionnaire
(49)
covers 30 negative thoughts proposed to occur during a symptom-atic depressed state.
In regard to psychodynamic psychotherapy, theory-specific 
mediators include measures of core conflicts
(50) and self-
understanding.(51)

Of all the treatments in medicine and psychiatry in particular, the evaluation of psychotherapy offers some of the greatest challenges to researchers. A wide variety of research designs and instruments have been employed, with distinct advantages and disadvantages to each. No one study of psychotherapy can answer all the important questions that need to be asked. Given the complexity of research on psychotherapy, knowledge accumulates slowly. Despite the problems, complexities, and slow pace of scientific advance, 6.1.2 the evaluation of psychological treatment

SECTION 6  treatment methods in psychiatry 1166
psychotherapy outcome research now has the tools and emerging 
findings to begin to influence the practice of psychotherapy 
and mental health treatments in general. We expect that in the next decade methodological advances in the evaluation of psychotherapy will lead to a stronger link between research and practice.
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46, 472–82.6.1.2 the evaluation of psychological treatment

Contents
 6.2.1 General principles of drug therapy in psychiatry
 6.2.2 Anxiolytics and hypnotics
 6.2.3 Antidepressants
 6.2.4 Lithium and related mood stabilizers
 6.2.5 Antipsychotic and anticholinergic drugs
 6.2.6 Antiepileptic drugs
Brian P . Brennan and Harrison G. Pope, Jr
 6.2.7 Drugs for cognitive disorders
 6.2.8 Drugs used in the treatment of the addictions
 6.2.9 Complementary medicines
 6.2.10 Non-pharmacological somatic treatments
 6.2.10.1 Electroconvulsive therapy
Max Fink
 6.2.10.2 Phototherapy
 6.2.10.3 Transcranial magnetic stimulation
 6.2.10.4 Neurosurgery for psychiatric disorders
Keith Matthews and David Christmas6.2.1 General principles of 
drug therapy in psychiatry

The successful use of psychotropic drugs demands an understand ing 
of their pharmaceutical, pharmacokinetic, and pharmacodynamic properties.
◆Pharmaceutical properties : Pharmaceutical formulations can be 
manipulated to produce different durations of action, for example the use of oily emulsions of antipsychotic drugs in depot formulations.
◆Pharmacokinetic properties : Pharmacokinetics is the mathe-
matical description of the disposition of drugs in the body by absorption, distribution (to plasma proteins and tissues), and elimination (usually by hepatic metabolism and renal excretion). Differences in drug disposition determine differences in dosage regimens and are important for drug interactions.
◆Pharmacodynamic properties : Pharmacodynamics is the study

◆Pharmacodynamic properties : Pharmacodynamics is the study 
of the pharmacological actions of drugs and how actions at the molecular level are translated, via actions at cellular, tissue, and organ levels, into therapeutic or adverse effects. The known phar-macological actions of psychotropic drugs are not necessarily the actions that produce their therapeutic or adverse effects.
Dosage regimens
A drug dosage regimen is a recipe for drug administration, intended to produce the desired therapeutic effect with a minimum of unwanted effects. It is described in terms of the pharmaceutical formulation, the dose, and the frequency and route of administra-tion used. The duration of administration is also important.
In treating any condition, it is best to learn initially to use a 
few drugs, preferably well-established ones, and to expand one’s repertoire with increasing experience.
The choice of drug depends ﬁ  rstly on the indication—obviously

The choice of drug depends ﬁ  rstly on the indication—obviously 
an antidepressant will be the drug of choice for a patient with depression, if drug therapy is thought to be required. The choice of Somatic treatments6.2

1169
antidepressant will depend on features of the disease and other 
factors. For example, some antidepressants are more sedative and 
anxiolytic than others, and can be helpful in patients who are 
agitated. The avoidance of adverse effects or interactions can also 
dictate the choice; for example, tricyclic antidepressants should be 
avoided in men with prostatic hyperplasia and selective serotonin 
reuptake inhibitors (SSRIs) should not be used in children, because 
of the increased risk of suicidal ideation.
It is usual to start therapy with published dosage recommendations, 
generally beginning at the lower end of the recommended dosage 
range and monitoring for a therapeutic effect. A common error is 
to give a starting dose of a drug and then to add or substitute 
another drug if the ﬁ  rst does not work. This is usually bad practice. 
If the desired effect does not occur with the initial dosage, increase 
the dose gradually until the effect occurs or the upper limit of the

the dose gradually until the effect occurs or the upper limit of the 
recommended range is reached (although adverse effects may limit 
this process). Only then should another drug be tried. Sometimes a 
poor response is due to poor adherence to therapy; careful expla-
nation of the condition and the need for therapy helps.
Psychotropic drugs can be given orally or parenterally, and as 
immediate-release or modiﬁ  ed-release formulations. Most drug 
administration is oral, but parenteral therapy can be useful to guar-
antee administration (e.g. depot formulations in schizophrenia) 
and for a quicker onset of action (e.g. in the treatment of acute 
mania). Modiﬁ  ed-release products are used for long-term therapy. 
They can be given less often and produce a smoother proﬁ  le of blood 
concentrations (Fig. 6.2.1.1).(1) The advantage of intramuscular

concentrations (Fig. 6.2.1.1).(1) The advantage of intramuscular 
modiﬁ  ed-release (depot) formulations of antipsychotic drugs is that 
drug delivery can be ensured by supervised infrequent administra-
tion (say every 2 weeks). Different modiﬁ  ed-release formulations 
of the same compounds have different release characteristics and 
are not interchangeable; for example, when prescribing a modiﬁ  ed-
release oral formulation of lithium always give the patient the same 
formulation and specify the brand name on the prescription.
Combination formulations (e.g. a phenothiazine plus a tricyclic 
antidepressant in a single tablet) do not allow ﬂ  exibility of prescrib-
ing and should generally be avoided. Important exceptions include 
combination analgesic formulations (e.g. co-codamol, which con-
tains paracetamol plus codeine) and combinations of levodopa with

tains paracetamol plus codeine) and combinations of levodopa with 
a dopa decarboxylase inhibitor (benserazide or carbidopa).
Treatment of children
There are no uniform rules for determining dosage regimens in 
children. Pharmacokinetics and pharmacodynamics are different 
for some drugs but not others.
◆ Absorption is not greatly different from absorption in adults.
◆ The distribution of water-soluble drugs is different, but psycho-
tropic drugs are lipid-soluble.
◆ Protein binding is reduced in neonates; phenytoin is affected.
◆ Hepatic oxidative metabolism and glucuronide conjugation 
are deﬁ  cient in neonates, and mature at variable rates; this is 
important for psychotropic drugs.
◆ Glomerular and renal tubular functions are immature in 
neonates and take about 6 months to reach adult values.

If a child needs a psychotropic drug, consult the manufacturer’s 
literature and always start with a low dosage.Treatment of elderly people
Pharmacokinetic differences in old age are more predictable than 
in children, but pharmacodynamic changes are variable.
◆ Absorption is not greatly affected.
◆ Elderly people have less body fat, and so lipid-soluble drugs 
may be more highly concentrated in the brain; however, this 
effect varies unpredictably from drug to drug (e.g. the apparent 
volume of distribution of diazepam is increased while that of 
nitrazepam is not).
◆ Protein binding is reduced in elderly people; phenytoin is affected.
◆ Hepatic metabolism is reduced in frail but not in ﬁ  t old people; 
this effect is proportional to liver size.
◆ Renal function is impaired with age; use creatinine clearance,

◆ Renal function is impaired with age; use creatinine clearance, 
measured or estimated (not eGFR), as a guide.
◆ Inappropriate polypharmacy is common in old people, increas ing 
the risk of drug interactions.
When treating an elderly person with a psychotropic drug always 
start with a low dosage and increase dosages more slowly.
Pregnancy and breast feeding
Anticonvulsants are teratogenic.(2) For example, sodium valproate 
has been associated with spina biﬁ  da, cardiac malformations, 
hypospadias, anomalies of the brain and face, coarctation of the 
aorta, and limb reduction defects.(3)
Few other psychoactive drugs are teratogenic. However, most of 
them cross the placenta and some can cause withdrawal symptoms 
in the neonate. The teratogenicity of lithium has been overstated 
in the past; the main risk is cardiovascular teratogenicity, but

in the past; the main risk is cardiovascular teratogenicity, but 
although the risk of Ebstein’s anomaly is increased, the absolute 
risk (0.05–0.1 per cent) is still very small;(4) nevertheless, some 
Fig. 6.2.1.1 Administration of lithium in immediate-release and modiﬁ  ed-release 
oral formulations. The immediate-release formulation (solid line) produces rapid 
peaks of serum concentration and large ﬂ  uctuations during a dosage interval. 
In contrast, the modiﬁ  ed-release formulation (dotted line) is more slowly 
absorbed but produces much less ﬂ  uctuation in serum concentrations. Note 
also that the apparent half-life of lithium is longer after administration of the 
modiﬁ  ed-release formulation; this is not the true half-life of lithium, but the 
half-life of its release from the modiﬁ  ed-release formulation. (Adapted from A.

half-life of its release from the modiﬁ  ed-release formulation. (Adapted from A. 
Amdisen, Variation of serum lithium concentration during the day in relation to 
treatment control, absorptive side effects and the use of slow-release tablets, Acta 
Psychiatrica Scandinavica , 207, 55–7, copyright 1969, John Wiley & Sons, Inc.)6.2.1 general principles of drug therapy in psychiatry

SECTION 6  treatment methods in psychiatry 1170
advise that it should be avoided or used with caution in the ﬁ  rst 
trimester of pregnancy,(5) and fetal sonography is recommended at 
18–20 weeks after ﬁ  rst-trimester exposure.(3)
Although most psychoactive drugs are lipid-soluble and therefore 
enter the breast milk, few do so in high enough amounts to trouble 
the neonate; if a neonate becomes drowsy while breast feeding, 
reduce the mother’s dosage or stop breast feeding. Lithium appears 
in the breast milk and can be found in the serum of breast-fed babies 
in variable concentrations, up to half of those in the mother. Because 
neonates have immature renal function, some recommend avoiding 
breast feeding.(6) However, others consider that the beneﬁ  ts of breast 
feeding to mother and child outweigh the small risk of lithium 
toxicity.(4) The following advice has been given:(3)
◆ Educate the mother about the manifestations of toxicity.
◆ Explain the risks of dehydration.

◆ Consider partial or total formula supplements during episodes 
of illness or dehydration.
◆ Suspend breast feeding if toxicity is suspected.
◆ Check infant and maternal serum concentrations.
Pharmacokinetics—drug disposition
Most psychotropic drugs are rapidly and well absorbed after 
oral administration. However, drugs can be removed by various 
processes before they reach the systemic circulation. The fraction 
of drug that reaches the systemic circulation is called its systemic 
availability (or, more commonly, bioavailability).
After oral administration a formulation will generally disintegrate 
in the stomach and the drug it contains will dissolve in gastric con-
tents. However, drugs are not generally absorbed in the stomach. 
After gastric emptying they are for the most part absorbed in the

After gastric emptying they are for the most part absorbed in the 
jejunum and ileum, and some are absorbed from the colon as well. 
During transit across the gut wall they may be metabolized by an 
oxidative isozyme of cytochrome P450, CYP3A4, and can be secreted 
back into the gut lumen by P glycoprotein. When they enter the por-
tal circulation they may be eliminated by the liver. If hepatic metabo-
lism is extensive, a large amount of drug will be removed during this 
ﬁ rst passage through the liver. For example, clomethiazole has exten-
sive ﬁ  rst-pass metabolism in the liver and its systemic availability is 
low (about 40 per cent); thus, intravenous doses are considerably 
lower than oral doses. In severe liver disease, such as cirrhosis, or 
when there is arteriovenous shunting, this presystemic metabolism is 
reduced and the systemic availability increases up to 90 per cent; oral

reduced and the systemic availability increases up to 90 per cent; oral 
doses of clomethiazole should be reduced in liver disease.(7)
In the systemic circulation drugs are bound to plasma proteins 
and distributed to the tissues. Protein binding is important for 
drugs that are highly bound (over 90 per cent) and not widely dis-
tributed to the body tissues; in those cases protein-binding dis-
placement can result in a large rise in the amount of unbound drug 
available to the target tissue. This is important for phenytoin, which 
is 90 per cent bound to plasma albumin and has a low volume of 
distribution. The binding of phenytoin is reduced when the serum 
albumin concentration falls (in chronic liver disease, the nephrotic 
syndrome, protein malnutrition, or the third trimester of pregnancy), 
when binding to the protein is abnormal (in chronic renal insufﬁ  -

ciency), or when another drug (e.g. sodium valproate) causes dis-
placement. Acute displacement causes phenytoin toxicity, but only transiently, because in the case of phenytoin an increase in unbound 
concentration causes it to be more rapidly eliminated. When 
measuring plasma phenytoin concentrations in patients in whom 
protein binding is reduced, the target concentration (and the labo-
ratory will measure total drug, i.e. bound plus unbound) is reduced 
(see Fig. 6.2.1.2).
In chronic renal insufﬁ  ciency the protein binding of phenytoin is 
reduced. This leads to an increase in the unbound plasma (or serum) 
concentration relative to the total concentration; the target total 
concentration therefore falls. The shaded area shows the range of 
plasma phenytoin concentrations that one would generally aim to

plasma phenytoin concentrations that one would generally aim to 
achieve (the target concentration range) in treating a patient with 
epilepsy. As renal function deteriorates (indicated here by an increase 
in serum creatinine concentration), the target range for plasma phe-
nytoin concentration falls from 40–80 μmol/l when renal function is 
normal to 10–30 μmol/l in severe renal insufﬁ  ciency.
After absorption and distribution most psychoactive drugs are 
cleared from the body by hepatic metabolism;(8) impaired liver 
function, if severe (for the liver has a large capacity), reduces their 
elimination, and dosages should be reduced.
Lithium is cleared solely by renal elimination and therefore the 
dosage should be reduced in proportion to the creatinine clearance. 
Since renal function falls with age, lithium dosages should be lower 
in older people.(9)
The half-life of a drug is a function of its clearance and its

The half-life of a drug is a function of its clearance and its 
distribution volume: the slower the rate of clearance or the more 
extensive the distribution the longer the half-life. If a drug is given 
in a regular maintenance dose, the amount of drug in the body 
will gradually accumulate; however, as the amount in the body 
increases, the rate at which it is eliminated also rises, and eventually 
a plateau (or steady state) is reached when the amount eliminated 
during a dosage interval equals the dose (the maintenance dose). 
The time it takes to reach this steady state depends on the half-life 
80
60
40
20
00 150 500 1000
Serum creatinine concentration ( μmol/l)Total phenytoin plasma concentration ( μmol/l)
1500
Fig. 6.2.1.2 In chronic renal insufﬁ  ciency the protein binding of phenytoin 
is reduced. This leads to an increase in the unbound plasma (or serum)

1500
is reduced. This leads to an increase in the unbound plasma (or serum) 
concentration relative to the total concentration; the target total concentration 
therefore falls. The shaded area shows the range of plasma phenytoin 
concentrations that one would generally aim to achieve (the target concentration 
range) in treating a patient with epilepsy. As renal function deteriorates (indicated 
here by an increase in serum creatinine concentration) the target range for plasma 
phenytoin concentration falls, from 40–80 μmol/l when renal function is normal 
to 10–30 μmol/l in severe renal insufﬁ  ciency (I. Odar-Cederlöf, unpublished data.)

1171
of the drug; about 94 per cent of the steady-state value will be 
reached after four half-lives (Fig. 6.2.1.3, curve A). For example, 
lithium has a half-life of about 24 h; after 4 days of maintenance 
therapy with the same regular dose a steady state will be reached; 
this does not depend on the dose or frequency of administration 
(Fig. 6.2.1.3, curves B and C). If a modiﬁ  ed-release formulation is 
used and the half-life of absorption of the drug from the formula-
tion is longer than the drug’s own half-life, the longer (apparent) 
half-life will determine the time to steady state; for example, the 
apparent half-life of ﬂ  upentixol after the administration of ﬂ  upen-
tixol decanoate is 17 days, compared with 36 h for ﬂ  upentixol after 
oral administration. When using depot antipsychotic drugs, which 
have long half-lives of absorption, steady-state therapy should ﬁ  rst 
be established with an ordinary formulation.

Curve A shows that during the regular administration of a main-
tenance dose of a drug the amount of drug in the body rises after a 
dose, reaches a peak, and then falls as the drug is distributed to the 
tissues and eliminated. If another dose is given soon after the ﬁ  rst, 
the plasma concentration will rise by the same amount as before 
but will fall faster after peaking, since most drugs obey ﬁ  rst-order 
kinetics and the plasma concentration falls exponentially. Thus, 
when a drug is given repeatedly the mean plasma concentration 
rises more slowly with each successive dose, until eventually a 
steady state is reached, when the amount eliminated in a dosage interval is equal to the dose itself. This takes about four half-lives of 
the drug. Curve B represents the concentrations during adminis-

tration of half the dose given at the same frequency. The time taken 
to reach steady state is the same in both cases, but the eventual 
steady-state concentration in case B is half that in case A, being 
proportional to the dose. Curve C represents the concentrations 
during administration of half the dose given twice as often (i.e. the 
total dose is unchanged). Neither the time taken to reach steady 
state nor the eventual mean steady-state concentration is affected. 
However, the ﬂ  uctuations in plasma concentration during a dosage 
interval are reduced (cf. Fig. 6.2.1.1). Kinetic characteristics of 
some psychotropic drugs are shown in Table 6.2.1.1.
Pharmacological actions of drugs
Psychotropic drugs interfere with neurotransmitter functions in 
several ways—via actions on neurotransmitter receptors, storage, 
release, reuptake, and metabolism. Transmembrane neurotransmit-

ter receptors are broadly speaking of two types—ionotropic and 
metabotropic receptors. Ionotropic receptors (e.g. nicotinic acetyl-
choline, glycine, GABA, and NMDA, AMPA, and kainate receptors) 
incorporate ion channels in their structures and mediate rapid 
responses. Metabotropic receptors (e.g. G protein-coupled recep-
tors such as adrenaline, noradrenaline, cannabinoid, dopamine, 
opioid, and serotonin receptors other than 5HT3 receptors) produce 
their effects via signal transduction systems, which activate second 
messengers or ion channels, and produce longer lasting responses.
Agonist action at a receptor
Agonists are substances that act by stimulating the action of a 
receptor.
Benzodiazepines bind to benzodiazepine receptors in the spinal

receptor.
Benzodiazepines bind to benzodiazepine receptors in the spinal 
cord, brainstem, cerebellum, limbic system, and cerebral cortex. 
These receptors are associated with receptors for the inhibitory 
neurotransmitter γ-aminobutyric acid (GABA), linked to a chlo-
ride channel.(10) The benzodiazepines enhance the action of GABA 
through its chloride channel, the presumed mechanism whereby 
they are anxiolytic and hypnotic. Some other hypnotics that have 
non-benzodiazepine structures also act via benzodiazepine 
receptors: zopiclone binds to the GABA–benzodiazepine receptor 
complex, but at a site different from that of benzodiazepines;(11)
clomethiazole binds to a binding site distinct from those of benzo-
diazepines and barbiturates;(12) zolpidem binds to a subtype of 
binding site called BZ1, found on GABA neurones in the sensorimo-
tor cortex and extrapyramidal tracts.(10)

The triptans (such as sumatriptan, naratriptan, zolmitriptan), 
which are used to treat migraine, are agonists at 5-hydroxytrypta mine 
(5-HT1B/D) receptors, causing vasoconstriction. They are therefore 
contraindicated in patients with cardiovascular disease and in those 
with hemiplegic or basilar migraine because of the fear of stroke.(13)
Antagonist action at a receptor
Antagonists are substances that have no actions of their own at 
receptors and act by preventing the action of an agonist, usually an 
endogenous one.
The antipsychotic (neuroleptic) drugs are all antagonists at recep-
tors for the endogenous neurotransmitter dopamine; this is thought 
to be the basis of their antipsychotic actions in the mesolimbic 
system (via Dl and D4 receptors) and undoubtedly produces their

system (via Dl and D4 receptors) and undoubtedly produces their 
Fig. 6.2.1.3 Curve A—during the regular administration of a maintenance dose 
of a drug the amount of drug in the body rises after a dose, reaches a peak, and 
then falls as the drug is distributed to the tissues and eliminated. If another dose is 
given soon after the ﬁ  rst, the plasma concentration will rise by the same amount 
as before but will fall faster after peaking, since most drugs obey ﬁ  rst-order kinetics 
and the plasma concentration falls exponentially. Thus, when a drug is given 
repeatedly the mean plasma concentration rises more slowly with each successive 
dose, until eventually a steady state is reached, when the amount eliminated in 
a dosage interval is equal to the dose itself. This takes about four half-lives of the

a dosage interval is equal to the dose itself. This takes about four half-lives of the 
drug. Curve B represents the concentrations during administration of half the dose 
given at the same frequency. The time taken to reach steady state is the same in 
both cases, but the eventual steady-state concentration in case B is half that in 
case A, being proportional to the dose. Curve C represents the concentrations 
during administration of half the dose given twice as often (i.e. the total dose 
is unchanged). Neither the time taken to reach steady state nor the eventual 
mean steady-state concentration is affected. However, the ﬂ  uctuations in plasma 
concentration during a dosage interval are reduced (cf. Fig. 6.2.1.1). (Adapted from 
Amdisen, A. Variation of serum lithium concentration during the day in relation to 
treatment control, absorptive side effects and the use of slow-release tablets, Acta

Psychiatrica Scandinavica , 207, 55–57. Copyright 1969, John Wiley & Sons, Inc.)6.2.1 general principles of drug therapy in psychiatry

SECTION 6  treatment methods in psychiatry 1172
adverse effects in the extrapyramidal tracts (via D2 receptors). The 
so-called atypical antipsychotic drugs (including clozapine and risperidone) have little effect on D
2 receptors and less commonly 
cause extrapyramidal adverse effects.(14)
Flumazenil is a competitive antagonist of benzodiazepines at 
benzodiazepine receptors and is used to reverse their effects.(15)
Partial agonist action at a receptor
Partial agonists are substances that can be agonists or antagonists at receptors, depending on the endogenous tone of the system upon which they are acting. If the degree of endogenous stimulation of the receptor is low, a partial agonist will tend to act as an agonist; if high, it will end to act as an antagonist.
The anxiolytic buspirone is a partial agonist at 5-HT
1A autore-
ceptors and reduces the ﬁ  ring of 5-hydroxytryptamine (5-HT) 
neurones by stimulating the auto-receptors.(16)
Actions via second messengers and ion channels

1A autore-
Some drugs act directly on second messenger systems and ion channels, without actions at receptors.
Lithium inhibits enzymes involved in the metabolism of inositol 
phosphates and may deplete cells of phosphoinositides, which are important as second messengers in neurotransmission.
(17)
However, other mechanisms have been proposed, including effects on the synthesis, turnover, and functional activity of brain 5-HT and effects on neuronal membrane function by effects on sodium and potassium ﬂ  uxes via the sodium/potassium pump 
enzyme.
(18)
Altered neurotransmitter storage
Reserpine, which causes depression, inhibits the incorporation of neurotransmitters into presynaptic storage vesicles and thus causes depletion of neurotransmitter stores.
Increased neurotransmitter release

Amphetamines cause increased release of noradrenaline (norepi-nephrine) and dopamine and have mood-enhancing effects.
(19)
Inhibition of neurotransmitter reuptake
Most antidepressants inhibit the reuptake of monoamines into the presynaptic nerve ending after their release.
(20) The effects of 
different antidepressants on monoamine reuptake are listed in Table 6.2.1.2. Reduced reuptake of monoamines occurs immedi-
ately, but the full therapeutic effects of antidepressants take some 
weeks to occur. This is explained by the occurrence of adaptive changes in presynaptic and postsynaptic receptors, including down-regulation of β-adrenoceptors, reduced sensitivity of β- and 
α
2-adrenoceptors, and increased sensitivity of αl-adrenoceptors

α
2-adrenoceptors, and increased sensitivity of αl-adrenoceptors 
and 5-HT receptors. However, it is not known how these actions are translated into the therapeutic effect. The last of these effects has led to the use of 5-HT autoreceptor antagonists, in the hope of producing a quicker onset of antidepressant action by enhancing 5-HT neurotransmission.
(21,22)  For example, the partial 
β-adrenoceptor agonist and 5-HT1A receptor antagonist pindolol 
hastens the response to SSRIs, although it does not affect the extent of the response.
(23) Another strategy involves drugs with 
several actions, which inhibit more than one reuptake system and are antagonists at neurotransmitter receptors.
(24)Table  6.2.1.1  Pharmacokinetic information about some 
Drug Systemic 
availability (%)Half-life (h) Route of hepatic 
eliminationa
Alprazolam 90 12 CYP3A
Chlordiazepoxideb 95 15
Clobazamb90 20
Diazepamb 100 30 CYP2E1/2C19
Flurazepamb 30 3 CYP2E1

Lorazepam 90 15Nitrazepam 75 24Oxazepam 100 9Temazepam 95 10
Antidepressonts
Lithium 100 24 (Renally excreted)
TricyclicsAmitriptyline 50 20 CYP1A2/2D6Clomipramine 50 20 CYP1A2/2D6/2C19Desipramine 40 24 CYP2D6Imipramine
b50 14 CYP1A2/2D6
Nortriptyline 60 36 CYP2D6TetracyclicsMaprotiline 95 40Mianserin 25 16 CYP2D6
Triazolopyridines
Trazodone 100 10Selective serotonin  
reuptake inhibitors
Fluoxetine 95 48 CYP2D6/3A4
Fluvoxamine 90 20 CYP1A2/2C19/3A4Paroxetine Variable 24 CYP2D6Sertraline Low 24 CYP2D6Monoamine oxidase  
inhibitors
Phenelzine High 1 Polymorphically 
acetylated
Tranylcypromine Moderate 2Moclobemide 40 2 CYP2C19
Antipsychotic drugs
Chlorpromazine
b 10 12
Thioridazine 60 10 CYP2D6Triﬂ  uoperazine Low 14Butyrophenones
Haloperidol 60 20 CYP2D6

b 10 12
Droperidol 75 2ThioxanthenesFlupentixol 40 36Zuclopenthixol 50 20 CYP2D6OthersClozapine 50 12Risperidone 75 3/20
c CYP2D6
a CYP refers to isozymes of the cytochrome P-450 family of enzymes.
b All these drugs are partly metabolized to active metabolites, Some of the metabolites 
have long half-lives (e.g. diazepam is metabolized to desmethyldiazepam). Some benzodiazepines (e.g. clorazepate and prazepam) are completely metabolized to active metabolites with long half-lives.
c Extensive and poor metabolizers respectively.

1173
Altered neurotransmitter metabolism
Inhibitors of monoamine oxidase (MAO) enhance monoamine 
neurotransmission by irreversibly and non-selectively inhibiting the breakdown of monoamines after their release. Moclobemide
(25)
is a RIMA, a reversible inhibitor of MAO type A, which metabolizes 5-HT and noradrenaline. Moclobemide is therefore less likely to cause hypertension when taken in combination with amine-containing foods, such as cheese, since this reaction requires inhibition of both MAO type A and MAO type B.
Valproate partly acts by inhibiting GABA transaminase, thus 
enhancing GABA inhibitory transmission. However, it has other actions: it inhibits GABA reuptake, increases the sensitivity of GABA receptors to GABA, reduces the concentrations of the excitatory neurotransmitter aspartate, and may open potassium channels, thus stabilizing neuronal cell membranes.
Adverse effects of drugs

Unwanted effects of drugs are commonly referred to as toxic effects or side effects. However, these are ambiguous terms, for several reasons:
◆ T oxic effects occur through exaggeration of the desired pharma-
cological action of the drug, and therefore occur at doses that are above those usually associated with a therapeutic effect. For example, antipsychotic drugs produce some toxic effects by antagonism at dopamine receptors in the extrapyramidal tracts.
◆ T oxic effects can also occur through exaggeration of actions 
other than those that are thought to produce the therapeutic action. Paracetamol toxicity occurs because an active metabolite binds covalently to liver proteins, damaging them.
◆ Side effects occur either through actions that are unrelated to the 
desired pharmacological effect or through actions that are related to the desired pharmacological effect but occur in another tissue.

desired pharmacological effect or through actions that are related to the desired pharmacological effect but occur in another tissue. 
Tricyclic antidepressants cause dry mouth, glaucoma, and urinary retention by anticholinergic action. Sildenaﬁ  l causes colour vision 
disturbances by inhibiting phosphodiesterase type V in the eye, the action by which it has its therapeutic effect in erectile dysfunction. True side effects are more properly called collateral effects.
(26)
It is therefore better to use the terms ‘unwanted effects’ or 
‘adverse effects/reactions’ . Adverse reactions and adverse effects are identical—the former are seen from the point of view of the patient, the latter from the point of view of the drug.
Adverse drug effects are classiﬁ  ed according to the scheme known 
as DoTS (Dose, Time, and Susceptibility).
(26)
Classiﬁ  cation according to dose-relatedness
1Hypersusceptibility reactions : Here the dose–response curve for

(26)
1Hypersusceptibility reactions : Here the dose–response curve for 
harm is far to the left of the dose–response curve for beneﬁ  t; hyper-
susceptibility adverse reactions therefore occur at doses below those that are normally beneﬁ  cial. Penicillin allergy is an example.
2Collateral reactions : Here the dose–response curve for harm is in 
a region that is bounded by a curve that is just to the left of the dose–response curve for beneﬁ  t and one that is just to the right; 
collateral adverse reactions therefore occur at doses within the range of those that are normally beneﬁ  cial. They can occur 
(i) through a pharmacological effect that is distinct from that involved in the beneﬁ  cial effect (for example an anticholinergic 
effect of a tricyclic antidepressant) or (ii) through the same pharmacological effect as that associated with the beneﬁ  cial

effect of a tricyclic antidepressant) or (ii) through the same pharmacological effect as that associated with the beneﬁ  cial 
effect, but in a different tissue (for example colour vision distur-bance due to sildenaﬁ  l).
3Toxic reactions : Here the harm occurs through the same mecha-
nism as beneﬁ  t (i.e. is on the same dose–response curve) but at 
doses that are above those that are normally beneﬁ  cial. An exam ple 
is serotonin syndrome due to ﬂ  uoxetine.
Classiﬁ  cation according to time-relatedness
Adverse drug reactions can be either time-dependent or time-
independent (Table 6.2.1.3).
1 Time-independent reactions can occur at any time during therapy

1 Time-independent reactions can occur at any time during therapy 
and are generally toxic reactions. They occur when the actual con-centration of the drug increases or dose response curve shifts to the left, for whatever reason. An example is digoxin toxicity, which can occur for pharmaceutical reasons (for example administra-tion of the wrong tablets), pharmacokinetic reasons (for example renal insufﬁ  ciency), or pharmacodynamic reasons (for example 
hypokalemia). In the ﬁ  rst two cases the concentration at the site 
of action increases and in the last the dose–response curve is shifted to the left.
2 Time-dependent adverse drug reactions are of six types; exam-
ples are given in Table 6.2.1.3.
◆ Immediate or rapid reactions occur when a drug is given too 
quickly.
◆ First-dose reactions occur only after the ﬁ  rst dose of a course.

quickly.
◆ Early reactions occur soon after the ﬁ  rst administration; they 
either wear off with time (early tolerant effects) or persist (early persistent effects).Table 6.2.1.2  Effects of antidepressants on monoamine reuptake
Drug Inhibition of uptake
Noradrenaline 5-HT Dopamine
Amitriptyline +++ ++ —Clomipramine +++ +++ —Desipramine +++ ++ —Imipramine
a++a+—
Nortriptyline ++ + —
Tetracyclics
Maprotiline ++ — —Mianserin ++ — —
Phenylethylamines
Venlafaxine ++ ++++ —
Trazodone — + —
Speciﬁ  c serotonin reuptake inhibitors
Fluoxetine — +++ —Fluvoxamine + ++ —Paroxetine — +++ —Sertraline + ++++ +
a Through its metabolite desipramine.6.2.1 general principles of drug therapy in psychiatry

SECTION 6  treatment methods in psychiatry 1174
◆ Intermediate reactions occur within the ﬁ  rst few weeks or 
months of administration but not thereafter; those who are susceptible will suffer the reaction and those who are not will not (healthy survivors); for example, clozapine causes neutro-penia predominantly during the ﬁ  rst 24 weeks of therapy—
there after the risk is small.
◆ Late reactions occur late in the course of administration, the 
risk increasing with time; this group includes withdrawal reactions.
◆ Delayed reactions are seen at some distant time after the initial 
exposure, even if the drug is withdrawn before the reaction appears.
Classiﬁ  cation according to susceptibility factors
The risk of an adverse drug reaction differs among members of 
an exposed population. For some reactions some individuals are susceptible, others are not—for example, prolonged muscle relax-

ation due to suxamethonium in people with pseudocholinesterase deficiency. In other cases susceptibility follows a continuous distribution—for example, increasing susceptibility with increas-ing impairment of renal function. Although reasons for increased susceptibility may be unknown, several types are recognized (Table 6.2.1.4).
(27–34)  These include:
◆ genetic variation;
◆ age;
◆ sex;
◆ physiological variation (for example pregnancy, body weight);
◆ exogenous factors (for example drugs and food);
◆ diseases (for example renal or hepatic impairment).
More than one susceptibility factor can be present in an individual.Table 6.2.1.3  Time-related classiﬁ  cation of adverse drug reactions in the DoTS method. (Reproduced from British Medical Journal , Aronson,

J.K. and Ferner, R.E. (2005), 327, 1222–5, with permission from BMJ Publishing Group Ltd.)
Type of reaction Examples Implications
Time independent
Due to a change in dose or 
concentration (pharmaceutical 
effects)Toxicity due to increased systemic availability Beware of changing formulations of some drugs 
(e.g. modiﬁ  ed-release formulations of lithium)
Due to a change in 
dose or concentration (pharmacokinetic effects)Lithium toxicity due to renal insufﬁ  ciency Forewarn the patient; monitor carefully throughout treatment; alter 
dosage when pharmacokinetics change (e.g. renal insufﬁ  ciency); avoid interacting drugs
Occurs without a change 
in dose (pharmacodynamic 
effects)Digitalis toxicity due to hypokalaemia Forewarn the patient; monitor carefully throughout treatment; avoid 
precipitating (pharmacodynamic) factors; avoid interacting drugs
Time dependent
Immediate (due to rapid 
administration)Red man syndrome (vancomycin)
Hypertension (digitalis)

Hypotension (iodipamide)Administer slowly
First dose [of a course] Hypotension (Ð1 adrenoceptor antagonists and angiotensin 
converting enzyme inhibitors)
Type I hypersensitivity reactions Take special precautions for the ﬁ  rst dose
Careful history taking; if a reaction occurs, avoid re-exposure; counsel 
the patient
Early tolerant
Early persistentAdverse reactions that involve tolerance 
(e.g. nitrate-induced headache)
Glucocorticoid-induced diabetes mellitusMonitor during the early stages; give appropriate reassurance; expect 
adverse effects if strategies to avoid tolerance are adopted
Monitor during the early stages and treat appropriately or withhold
Intermediate (risk increases at 
ﬁ  rst, then diminishes)Venous thromboembolism (classical antipsychotic drugs)
Neutropenia (clozapine)

Hypersensitivity reactions types II, III, and IVMonitoring not needed after the high-risk period unless 
susceptibility changes; withdraw drug if a reaction develops
Late (risk increases with time) Osteoporosis (glucocorticosteroids)
Tardive dyskinesia (dopamine receptor antagonists)Retinopathy (chloroquine)Tissue phospholipid deposition (amiodarone)Withdrawal syndromes: opiates, benzodiazepines, 
hypertension (clonidine and methyldopa), myocardial infarction (beta-blockers)Assess baseline function; forewarn the patient; monitor periodically 
during prolonged treatment
Withdraw slowly; forewarn the patient; replace with a longer acting 
drug if withdrawal is not possible
Delayed Carcinogenesis (ciclosporin, diethylstilbestrol)
Teratogenesis (thalidomide)Avoid or screen; counsel or forewarn the patient

1175
Factors that increase the risk of an adverse effect
(a) Pharmaceutical factors
Adverse effects can arise from changes in the pharmaceutical 
formulation. There is a risk of lithium toxicity or loss of action when one modiﬁ  ed-release formulation of lithium is replaced by 
another.
(b) Pharmacokinetic factors
Changes in the pharmacokinetics of a drug can result in toxic or collateral adverse effects. This most commonly occurs through impaired liver function (Table 6.2.1.1) or renal insufficiency (lithium).
(c) Pharmacodynamic factors
Changes in the sensitivity of a tissue to a drug occur during long-term therapy and can result in adverse effects. Tardive dys kinesia with dopamine receptor antagonists may be related to altered sensitivity of dopamine receptors,
(35) although there are problems 
with this hypothesis, and complex interactions with other neurotr ans-
mitters may be involved.(36)
When adaptive changes occur during long-term therapy, sudden

When adaptive changes occur during long-term therapy, sudden 
withdrawal of the drug can result in rebound reactions. Examples include the typical syndromes that occur after the sudden withdra wal 
of narcotic analgesics
(37, 38)  or of alcohol (delirium tremens).(39)
Sudden withdrawal of barbiturates can cause restlessness, sleepless-ness, mental confusion, and convulsions; a similar syndrome, in which anxiety features prominently, can occur after the sudden withdrawal of benzodiazepines.
(24, 40)
Drug interactions
In a drug interaction one drug alters the effects of another, result-ing in increased or decreased effects. Fluvoxamine inhibits the hepatic metabolism of warfarin and increases its anticoagulant effect,
(41) whereas carbamazepine reduces the anticoagulant effect 
of warfarin by increasing its metabolism.(42)

1 Pharmaceutical interactions occur when there is a physicochem-
ical interaction between two compounds in solution. Lists of such incompatibilities are too long to remember. T o avoid phar-
maceutical interactions, do not combine drugs in an infusion solution and use only sodium chloride 0.9% or glucose 5% in drug infusions.
2 Pharmacokinetic interactions occur when one drug interferes 
with the disposition of another during absorption, distribution, or elimination. Here are examples that are relevant to psycho-tropic drugs.
◆ Sucralfate reduces the absorption of amitriptyline by about 
50 per cent;(43) this might be of clinical importance, but drug 
absorption interactions are not usually important.
◆ Phenytoin is displaced from protein-binding sites by valproate 
(which also inhibits its metabolism).(44)
◆ The metabolism of psychotropic drugs can theoretically be

◆ The metabolism of psychotropic drugs can theoretically be 
inhibited by drugs that inhibit metabolism via cytochrome P450 in the liver (Table 6.2.1.1). Reports of such interactions appear frequently. Inhibitory drugs include cimetidine, antifungal imidazoles (such as ﬂ  uconazole), and macrolides 
(such as erythromycin).
◆ Non-selective MAO inhibitors, such as tranylcypromine, 
inhibit the metabolism (by MAO type A) of dietary amines in the gut and metabolism (by MAO type B) of the noradrena-line that they release, resulting in hypertension. Avoid this combination.
◆ Diuretics inhibit the renal excretion of lithium; alter the 
dosage of lithium and monitor the serum concentration when starting a diuretic or changing the diuretic dosage.
3 Pharmacodynamic interactions occur when two drugs interact

3 Pharmacodynamic interactions occur when two drugs interact 
at the same site of action. Alcohol potentiates the actions of all psychotropic drugs; patients taking psychotropic drugs should be warned that even one alcoholic drink can impair their ability to drive or operate machinery. The combination of reuptake inhibitors with non-selective irreversible monoamine oxidase inhibitors can cause the serotonin syndrome,
(45) which is Table 6.2.1.4  Sources of susceptibility to adverse drug reactions
Source of susceptibility* Examples Implications
Genetic Porphyria
Suxamethonium sensitivity
Malignant hyperthermia
CYP isozyme polymorphismsScreen for abnormalities; avoid speciﬁ  c drugs
Age Neonates (chloramphenicol(27))
Elderly people (hypnotics(28))Adjust dosages according to age
Sex Alcohol intoxication
Meﬂ  oquine, neuropsychiatric effects(29)

Lupus-like syndrome(30)Use different doses in men and women
Physiology altered Phenytoin in pregnancy(31) Alter dosage or avoid
Exogenous factors Drug interactions
Interactions with food (e.g. grapefruit juice with drugs cleared by 
CYP3A4(32); see Table 6.1)Alter dosage or avoid co-administration
Diseases Renal insufﬁ  ciency (e.g. lithium(33))
Hepatic cirrhosis (e.g. morphine(34))Screen for abnormalities; avoid speciﬁ  c drugs; use reduced 
dosages
*Mnemonic GASPED6.2.1 general principles of drug therapy in psychiatry

SECTION 6  treatment methods in psychiatry 1176
sometimes fatal.(46) The combination of lithium with either 
SSRIs(47) or the SNRI venlafaxine(48) can also cause the serotonin 
syndrome. Flumazenil reverses the effects of benzodiazepines—a beneﬁ  cial pharmacodynamic interaction.
Monitoring drug therapy
If possible, monitor drug therapy by observing the clinical 
outcome. In psychiatric disorders this is difﬁ  cult, but it can be done 
by asking patients or their carers to keep diaries of symptoms.
Next best is to monitor some pharmacological effect of the drug, 
in the way that one measures the international normalized ratio (INR) in patients taking warfarin (thus measuring the effect of the drug on the blood, being unable to monitor its clinical effect of preventing pulmonary embolism). However, there are no compa-rable routine tests available for monitoring the pharmacological effects of psychotropic drugs.
Because of these difﬁ  culties one falls back on measurements of

Because of these difﬁ  culties one falls back on measurements of 
serum concentrations of some drugs. The assumptions in doing this are that the serum concentration reﬂ  ects the concentration at 
the site of action and that there is a concentration–effect relation-
ship. Few psychoactive drugs can be monitored in this way, the principal ones being lithium and phenytoin. Some advocate moni-toring treatment with some tricyclic antidepressants,
(49) but this 
use is controversial.
Serum concentration measurement can be used to individualize 
therapy in the early stages of treatment or when the dosage is being changed, to check adherence to therapy, to help diagnose toxicity, and to monitor the effects of drug interactions.
Carbamazepine
The target plasma carbamazepine concentration range is 17–42 mmol/l, but plasma concentrations do not correlate well with effect, since it has an active metabolite, oxcarbazepine; higher concentrations are associated with an increased risk of toxicity.

(50)
Carbamazepine induces its own metabolism, and its half-life is therefore shortened during long-term therapy. So, after an initial apparent steady state has been reached 3 or 4 days after starting therapy, a new steady state occurs at a lower concentration a few weeks later, and the dose may need to be increased at that time. Blood samples should be taken immediately before a dose.
Lithium
The target serum lithium concentration is 0.4–1.0 mmol/l. Concentrations above 1 mmol/l are associated with an increased risk of toxicity. Take blood samples at a standard time—12 h after the last dose. In my view, routine monitoring is unnecessary, and the serum lithium concentration should be measured at times when toxicity is most likely, for example in patients with changing renal function or with acute alterations in electrolyte balance.
(51,52)

(51,52)
Many psychiatrists prefer to measure the serum lithium concentra-tion routinely at, say, 3- or 6-monthly intervals. However, although regular monitoring may emphasize the dangers to the patient and give an opportunity for a consultation, it is no substitute for proper monitoring at the appropriate times.
Valproate
The target serum valproate concentration range is 40–80 μmol/1, although this range is based on its use in epilepsy rather than bi polar affective disorder;
(53) higher concentrations are associated with an 
increased risk of toxicity. The blood sample can be taken at any time after the last dose.
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SECTION 6  treatment methods in psychiatry 1178
6.2.2 Anxiolytics and hypnotics
Anxiety is a commonly experienced emotion that becomes a clinical 
disorder when it is too severe, too protracted, or too pervasive for the subject to bear. Insomnia is a failure to experience satisfying sleep, together with a feeling of tiredness during the day. Many compounds, the anxiolytics and hypnotics, are used to treat these conditions, but the two groups of drugs overlap.
The classical antianxiety drugs (anxiolytics) are alcohol, the 
opioids, and the barbiturates. For the past 45 years, the benzodiaz-epines, such as diazepam and lorazepam, have dominated the ﬁ  eld. 
They are effective anxiolytics in the short term but their long-term efﬁ cacy remains in dispute. Their disadvantages include cognitive 
and psychomotor impairment, paradoxical reactions, tolerance, and dependence, and they are major drugs of abuse.
Other anxiolytics act on the 5-hydroxytryptamine (5-HT;

Other anxiolytics act on the 5-hydroxytryptamine (5-HT; 
serotonin) systems of the brain and include buspirone and the 
selective serotonin reuptake inhibitors (SSRIs). Newer compounds are still being introduced that lie outside these groups.
The use of benzodiazepine and benzodiazepine-like hypnotics, 
by contrast, continues apace. Some switching to the shorter-acting benzodiazepines has occurred, together with the introduction of the ‘z-compounds’ , zopiclone, zolpidem, and zaleplon. These drugs tend to have fewer residual effects the next day than the benzodiaz-epines, and are claimed to be less likely to induce rebound and dependence than equivalent benzodiazepines. Particular care is needed in prescribing such hypnotics to the elderly.
The rational use of both anxiolytics and hypnotics requires

The rational use of both anxiolytics and hypnotics requires 
minimal dosage, short durations of use, and simultaneous exploitation of non-pharmacological methods.
‘Sedative’ originally meant a substance that has the property of 
allaying anxiety. However, it has now come to denote feelings of drowsiness or torpor. This state was originally called ‘oversedation’ , and was often noted with the barbiturates and other older drugs such as chloral. Next, the term ‘tranquillizer’ was introduced 40 or more years ago in an attempt to distinguish between the older sedatives and the newer drugs, supposedly non-sedative, such as the benzodiazepines. But this distinction is artiﬁ  cial as, apart from 
safety in overdosage, the benzodiazepines closely resemble the barbiturates in pharmacological and clinical properties. The term ‘anxiolytic’ is now generally favoured.
Anxiolytic drugs

Anxiety-allaying drugs have been used for thousands of years, dating back to the discovery that, among its psychotropic proper-ties, alcohol could induce sedation. The nineteenth century saw the development of inorganic and, later, organic chemical compounds. Bromides were introduced as sedatives and became widely used despite their poor effectiveness, toxicity, and potential abuse. Organic chemists in the second half of the nineteenth century 
introduced sedatives such as chloral and paraldehyde.
The ﬁ  rst barbiturate was introduced over a 100 years ago. This

The ﬁ  rst barbiturate was introduced over a 100 years ago. This 
group of drugs is divisible into the ultrashort-acting (e.g. anaes-thetic-induction agents such as thiopentone and methohexital), short-acting (e.g. secobarbital), medium-acting (e.g. butobarbital), and long-acting (e.g. phenobarbital) barbiturates. Most of the rest are of medium duration with half-lives of 16 h or so. The disadvan-tages of the barbiturates include drowsiness, tolerance to their effects, dangers of overdose, and possible physical and psychological dependence with severe withdrawal syndromes.
(1)
Meprobamate was introduced as the ﬁ  rst of the ‘tranquillizers’ , but 
its advantages over the barbiturates proved minimal.
The benzodiazepines were ﬁ  rst synthesized in the 1930s, but

(1)
The benzodiazepines were ﬁ  rst synthesized in the 1930s, but 
not developed until 2 years later. The prototype, chlordiazepoxide, was evaluated in the clinic, found effective, and soon introduced into medical practice. More than 1000 benzodiazepines and related compounds have been synthesized, including diazepam, the most widely used of all. Anxiolytic and hypnotic, as well as muscle-relaxant and anticonvulsant properties are licensed indications. However, the distinction between anxiolytic and hypnotic uses often seems to owe more to commercial expediency than to scien-tiﬁ c rationale; some compounds, such as lorazepam, are marketed 
for both indications.
The benzodiazepines

The main reason for the original popularity of the benzodiazepines was the perceived safety in overdose compared with the quite marked toxicity of the barbiturates. In turn, concern has mounted concerning the benzodiazepines.
(2) These drugs are widely prescribed 
by many physicians for patients with emotional problems, circula-tory disorders, tension headaches, and pains in the chest and back as well as digestive disorders, all with the common symptom of anxiety. This widespread use, even overuse and the induction of dependence even at normal therapeutic dose has led to ofﬁ  cial 
injunctions for greater caution in prescribing.
Pharmacokinetics
Two aspects of the pharmacokinetics of the benzodiazepines are 
relevant to the prescriber—speed of onset of action and the dura-tion of that action. The speed of onset depends on the mode of

relevant to the prescriber—speed of onset of action and the dura-tion of that action. The speed of onset depends on the mode of 
administration and the penetration time to the brain. Given by mouth, most benzodiazepines are rapidly absorbed and exert a prompt anxiolytic effect, for instance in panic states. Diazepam and lorazepam are prime examples. Although temazepam enters the brain more rapidly than, say, oxazepam, it still takes an appreciable time to induce sleep. The redistribution phase can be pronounced and will then largely determine the duration of effect of single doses of benzodiazepines such as diazepam and ﬂ  unitrazepam.
The metabolic half-lives of the benzodiazepines also vary greatly. 
N-desmethyldiazepam (nordiazepam) is the major and active 
metabolite of diazepam and several other benzodiazepines. It has a long half-life, about 60 h, and accumulates over the ﬁ  rst month of

metabolite of diazepam and several other benzodiazepines. It has a long half-life, about 60 h, and accumulates over the ﬁ  rst month of 
treatment. Metabolism of these drugs is even slower in the elderly and in patients with liver damage.
Benzodiazepines with a 3-hydroxyl grouping, such as lorazepam, 
oxazepam, and temazepam, have half-lives averaging 12 h or less. Liver damage has to be severe before the metabolism of these drugs

1179
is affected. Alprazolam is a triazolobenzodiazepine with a half-life 
of 9 to 16 h, and with hydroxy metabolites of low biological activity. 
Both chlordiazepoxide and diazepam are absorbed erratically after intramuscular injection. Lorazepam, however, is well absorbed after intramuscular injection.
Basic pharmacology
The benzodiazepines potentiate the widespread inhibitory neu-rotransmitter γ-amino butyric acid (GABA). Benzodiazepines do 
not act directly on GABA receptors but have their own receptors. Because of this widespread inhibitory effect, benzodiazepines alter the turnover of neurotransmitters such as norepinephrine and sero-tonin. The main sites of action of the benzodiazepines are in the spi-nal cord where muscle-relaxant effects are mediated, the brainstem (perhaps accounting for their anticonvulsant properties), the cere-bellum (causing ataxia), and the limbic and cortical areas involved in the organization of emotional experience and behaviour.
Clinical pharmacology

The depressant effects of single therapeutic doses of a benzodiaze-pine can usually be readily detected. However, lower doses may fail to impair psychological functioning and subjective effects are usually absent. In the clinical context with anxious patients and with repeated higher doses, sustained impairment of functioning is more difﬁ  cult to demonstrate. Some studies have shown decre-
ments in performance after the ﬁ  rst dose, but improvements in 
functioning, in comparison to predrug levels, may become apparent by the end of a week of repeated usage. This suggests that the well-known impairment of performance produced by pathologi-cally high levels of anxiety is ﬁ  rst worsened by the sedative effects. 
Then as the antianxiety effects build-up, the patient’s psychological functions may improve.
A second mechanism concerns tolerance, which reﬂ  ects several

A second mechanism concerns tolerance, which reﬂ  ects several 
biochemical mechanisms including alteration in benzodiazepine-receptor type. Patients who have a high alcohol intake are tolerant to benzodiazepines.
The benzodiazepines have marked and selective effects on 
memory by interfering with episodic memory, that is to say the system concerned with remembering personal experiences.
(3) This 
effect seems independent of any sedation or attentional impairment. Alcohol adds to the cognitive impairment induced by the benzodi-
azepines but does not necessarily potentiate it.
The dependence potential of benzodiazepines is seen in drug-
preference studies, but these drugs are much less preferred than say the amphetamines. Differences among benzodiazepines have been documented; for example, oxazepam seems to have less abuse liability than diazepam.

The largest gap in our knowledge of these drugs is on their long-
term usage, which has been evaluated in relatively few studies.
(4)
Thus, it is still largely unclear whether therapeutic effects are main-tained in most patients for longer than a few weeks and when dependence supervenes in the minority of patients who encounter problems on protracted usage.
Hypnotic drugs
The main groups of drugs used in the modern treatment of insom-nia are the benzodiazepines, and the newer compounds, zopiclone, eszopiclone, zolpidem, and zaleplon. The pharmacology of these 
benzodiazepines is essentially the same as that of the anxiolytic 
compounds.
Nitrazepam is a long-acting benzodiazepine with an elimination 
half-life ranging between 25 and 35 h, but it is longer in the elderly.

Because of this, it is likely to produce residual effects and to accumulate. Flunitrazepam is more potent, but is somewhat shorter acting with a half-life of 10 to 20 h. It has a rapid redistribu-tion phase, which can result in a short duration of intense action. It has earned an undeserved reputation as the ‘date-rape’ drug. Flurazepam is still widely used in the United States. It has a very long-acting metabolite, which can produce psychological impair-ment on regular dosage, especially in the elderly. Of the intermediate-acting compounds, temazepam has a half-life of 10 to 15 h, without active metabolites. At modest dose (10–15 mg daily), it results in few residual effects and is fairly well tolerated by the elderly. Major problems with abuse have limited its popularity, but it is still widely prescribed worldwide. Lormetazepam is slightly shorter acting, loprazolam has a fairly short half-life, but its absorption may be slow and erratic.

Triazolam is the archetypal short-acting benzodiazepine, with a 
mean half-life of around 3 to 4 h, and no clinically signiﬁ  cant 
metabolites. Daytime sedation is seen after high doses (0.5 mg daily), but not usually with lower ones. These higher doses have also been associated with an increased incidence of anterograde amnesia and unusual behaviours, including depressive reactions and hostility.
Zopiclone is a cyclopyrrolone derivative believed to bind close 
to, but not exactly at, the benzodiazepine receptor. It has a half-life of about 5 h in younger subjects and about 8 h in the elderly. Its sedative and hypnotic effects are similar to those of the benzodi-azepines, but its side effect proﬁ  le is generally superior with fewer 
central nervous system effects such as oversedation, confusion, and memory impairment. Rebound and withdrawal problems also seem to be less.
Eszopiclone is the S-enantiomer of zopiclone, which is a racemic

Eszopiclone is the S-enantiomer of zopiclone, which is a racemic 
mixture. It is licensed for the long-term treatment of insomnia in the United States, following successful clinical trials.
Zolpidem is an imidazopyridine compound that binds selectively 
to one subtype of the benzodiazepine receptor. It is rapidly absorbed 
and has a short elimination half-life of 0.7 to 3.5 h (mean 2.4 h). It decreases sleep-onset latency but has less consistent effects on total sleep time.
(5) Residual effects are minimal, as are memory 
disturbances. Rebound and withdrawal are uncommon but have been documented.
Zaleplon is also a selective compound with a very short half-life 
averaging only 1 h. It shortens sleep onset without usually prolong-ing total sleep time. Residual effects are absent, and memory is minimally disturbed.
Clinical effects of anxiolytics
Although the usual licensed indications are generalized anxiety and panic disorder,
(6, 7) the main practical application of the benzodiaz-

epines is to aid in the symptomatic management of anxiety and stress-related conditions.
(8) These indications are often so wide as to 
be difﬁ  cult to deﬁ  ne in terms of recognized disorders. Instead the 
symptoms of anxiety, in whatever context, are the main indication. 6.2.2 anxiolytics and hypnotics

SECTION 6  treatment methods in psychiatry 1180
Thousands of comparative trials among the benzodiazepines have 
been carried out, but few differences with respect to risk–beneﬁ  t 
ratios have been found.
Antianxiety medications are difﬁ  cult to assess. Anxiety disorders 
are very varied in their natural history; some resolve over a few 
weeks, whereas others become chronic for no apparent reason, with subsequent acute-on-chronic exacerbations. The patients with chronic, severe unresponsive illnesses tend to be referred to psychi-atric outpatient departments. Uncontrolled observations on family practice patients will give a more encouraging impression of anti-anxiety drugs than will assessment of the more chronic patients attending psychiatric clinics. Even in the latter type of patient, useful symptomatic relief is often obtained without complete resolution of the illness.
Drugs such as diazepam have a long elimination half-life so that

Drugs such as diazepam have a long elimination half-life so that 
once daily or nightly dosage is sufﬁ  cient. Nevertheless, many 
patients prefer to take a divided dosage during the day, often claim-ing that they can detect further antianxiety activity after each dose and are thereby reassured. For episodic anxiety, shorter-acting compounds such as lorazepam can be used, taken 30 min or so before entering the anxiety-provoking situation. If the panic has already started, lorazepam can still be given and will exert a fairly prompt action. Lorazepam is also invaluable in the emergency man-agement of the acutely anxious and disturbed psychotic patient.
Antipanic actions have been claimed for the benzodiazepines, in 
particular alprazolam, acting to prevent the episodes rather than aborting them. However, although suppression of the panic attack is often quite effective, relapse, and even rebound may occur when the benzodiazepine is discontinued, even if it is tapered off.
(9)

(9)
Because of this SSRI antidepressants are generally preferred.(7)
The short-acting benzodiazepines are also used as adjuncts to 
relaxation therapy, preoperative medication, and deep sedation for minor operative procedures such as dentistry. The drugs render the patient calm, conscious, and cooperative, with often total antero-grade amnesia for the operation.
Unwanted effects
The commonest unwanted effects of the anxiolytic benzodiazepines 
are tiredness, drowsiness, and torpor, features of ‘oversedation’ . The effects are dose and time related, being maximal within the ﬁ rst 2 h after large doses. Drowsiness is most noticeable during 
the ﬁ  rst week of treatment, after which it largely disappears proba-

bly due to a true tolerance effect. Patients should be warned of the potential side effects of any prescribed benzodiazepine and the initial dosage should be cautious. Both psychomotor skills and intellectual and cognitive skills are affected. In particular, patients should be advised not to drive during the initial adjustment of dosage. Important decisions should be deferred during this period because judgement may be clouded.
Benzodiazepines have major effects on cognitive function in 
long-term users. A meta-analysis of 13 research studies revealed 
impairments across all cognitive categories examined.
(4) The drugs 
differ in their ability to produce memory deﬁ  cits, with lorazepam 
being especially powerful.(3) However, most benzodiazepines can 
cause problems, especially in higher dose and in the elderly.
Psychomotor performance is also affected, with elderly drivers

Psychomotor performance is also affected, with elderly drivers 
particularly at risk. As with other depressant drugs, potentiation of the effects of alcohol can occur. Patients must be warned not to drink alcohol when taking benzodiazepines, either chronically or intermittently. Patients taking benzodiazepines may develop 
paradoxical behavioural responses such as uncontrollable weeping, increased aggression and hostility, and acute rage reactions or uncharacteristic criminal behaviour such as shoplifting.
(10) This 
phenomenon is by no means conﬁ  ned to the benzodiazepines; 
alcohol is a cardinal example of a drug whose use may lead to excessive violence or criminal behaviour. Paradoxical reactions, including the release of anxiety or hostility, are most common 
during the initial week of treatment, and usually resolve spontane-

ously or respond to dose adjustment. Reports of the induction of depression by the benzodiazepines in patients with apparent generalized anxiety disorder are probably the result of an initial misdiagnosis and a failure to detect the underlying depression.
Other unwanted effects include respiratory depression, excessive 
weight gain, skin rash, impairment of sexual function, menstrual irregularities, and rarely, blood dyscrasias. The use of benzo-diazepines in pregnancy is generally regarded as reasonably safe. However, benzodiazepines pass readily into the foetus and can produce respiratory depression in the neonate. Finally, benzodiaz-epines pass into the mother’s milk and can over sedate the baby, so breastfeeding should be discouraged if benzodiazepines are pre-scribed, especially in high dose.
Overdosage

Overdosage with benzodiazepines is common; deaths are not. Although fatal-overdose statistics contain deaths ascribed to benzodiazepines alone,
(11) many such attributions are suspect. 
Only in children and the physically frail, especially those with respiratory illness, are the benzodiazepines on their own hazardous. However, they can markedly potentiate other central nervous system depressant drugs such as alcohol. Typically, the person falls into a deep sleep but can be roused the administration of the benzodiazepine antagonist, ﬂ  umazenil.
Tolerance and dependence
If tolerance occurred regularly, then escalation of dosage would be

If tolerance occurred regularly, then escalation of dosage would be 
the norm. This does occur with the benzodiazepines, but is fairly uncommon. Escalation of dose is often stepwise, with each incre-ment following a temporary deterioration in psychosocial circum-stances. Most patients later reduce the dose as the stress resolves, but others continue the higher dose to which they presumably have developed some tolerance.
T olerance to the clinical effects in patients maintaining moderate 
doses of benzodiazepines is now generally accepted.
(12) Few con-
trolled observations concern the long-term efﬁ  cacy of anti anxiety 
compounds in chronically anxious patients. If medication is withdrawn, the original symptoms may reappear. This is taken as evidence that therapeutic benefit still continues. However, it may reﬂ  ect ‘rebound’ rather than long-term clinical beneﬁ  t.

Undoubtedly, many chronically anxious patients are helped by their treatment with benzodiazepines, but this raises the question as to the frequency of psychological and physical dependence on these drugs. Dependence is easily demonstrable in those patients who have attained high doses. Rebound and withdrawal symptoms after the long-acting benzodiazepine diazepam are not usually apparent until about 5 to 10 days after discontinuation. It is much shorter in patients discontinuing the shorter-acting benzodiaze-pines (2–4 days). The mildest symptoms and signs are anxiety, tension, apprehension, dizziness, tremulousness, insomnia, and

1181
anorexia. More severe physical dependence is shown by the with-
drawal symptoms of nausea and vomiting, severe tremor, muscle 
weakness, postural hypotension, and tachycardia. Occasionally, 
hyperthermia, muscle twitches, convulsions, and confusional 
psychoses may develop.
After normal dose usage, perceptual changes can be particularly 
troublesome.(13) The proportion of patients taking benzodiaze-
pines chronically who experience withdrawal symptoms on discon-
tinuing medication ranges between 27 and 45 per cent, depending 
on the criteria used. Sometimes the withdrawal reactions seem very 
prolonged(14) or depression may supervene.
Management of withdrawal
It is widely accepted that the most appropriate way to manage 
patients withdrawing from benzodiazepines is to taper the dose 
gradually, because the severe symptoms of withdrawal, such as 
epileptic ﬁ  ts and confusional episodes, are more likely to follow 
abrupt than gradual withdrawal. Views differ as to the rate of

abrupt than gradual withdrawal. Views differ as to the rate of 
withdrawal. Detailed guidelines,(15,16) based on a consensus view 
in the United Kingdom, recommend minimal intervention ﬁ  rst, 
usually by a general practitioner (Fig. 6.2.2.1). This may comprise a letter to the long-term user, or an interview on a routine visit, 
with advice to taper the medication. More active intervention 
involves careful assessment, education, and then the adoption, with 
the patient’s agreement, of a timetable of about 6 to 8 weeks for 
withdrawal. Some agencies suggest a month of tapering for every 
year of benzodiazepine use, but this may result in patients becom-
ing preoccupied with their symptoms. One strategy is to try a fairly 
brisk withdrawal, say over 6 to 8 weeks, and only resort to more 
gradual tapering if the symptoms become intolerable. Another ploy

gradual tapering if the symptoms become intolerable. Another ploy 
is ﬁ rst to substitute a long-acting for a short-acting benzodiazepine, 
say 10 mg of diazepam for 1 mg of lorazepam, and then to taper off 
the diazepam later.
Patients must be carefully followed up as a depressive illness is 
not uncommon and may need vigorous treatment. Such an illness 
may be reactive to the stress of withdrawal or be a recurrence of an 
earlier affective episode.
Other drugs have been advocated, but most patients are loath to 
substitute yet another medication. Depressed patients should have 
the depression treated before attempting withdrawal. Based on 
evidence from animal studies, fairly large single doses of ﬂ  umazenil 
have been tried with some success.
Psychological support is essential, with the doctor or a practice 
nurse maintaining close contact with the patient during withdrawal.

nurse maintaining close contact with the patient during withdrawal. 
The physician should show clearly that he understands the prob-
lems of withdrawal in order to capture the conﬁ  dence of the 
patient. He or she must recognize that patients frequently incubate 
numerous misconceptions and negative expectations about 
tranquillizers and withdrawal. These must be elicited, identiﬁ  ed, 
discussed, and corrected.
Cognitive behavioural treatment is currently favoured and is 
often effective if administered by an experienced professional. 
Relaxation treatment and training in anxiety management skills 
in the framework of group therapy can boast of only moderate 
effectiveness.
Other anxiolytics
Benzodiazepine-receptor partial agonists
The disadvantages of the benzodiazepines include sedation, 
psychomotor and cognitive impairment, and withdrawal

psychomotor and cognitive impairment, and withdrawal 
symptoms after long-term use. Increased understanding of benzo-
diazepine-receptor mechanisms suggested that compounds 
might be developed which are partial agonists and/or selective to 
some subtypes of receptor.(17) Such compounds would be less 
efﬁ cacious than full agonists but might have better adverse-effect 
proﬁ les and less dependence potential, that is superior risk–beneﬁ  t 
ratios. Their promise has not been fulﬁ  lled, as the risk–beneﬁ  t 
ratios of these compounds do not seem superior to those of the 
full agonists.
5-HT1A partial agonists
These drugs have a complex pharmacology. The ﬁ  rst, buspirone, 
was licensed in many countries some years ago. These drugs 
suppress activity in presynaptic serotonergic neurones, diminish-

ing serotonin activity, and leading on to down-regulation of 5-HT2
and perhaps other 5-HT receptors. Buspirone is much less 
sedative than the benzodiazepines and causes little or no psycho-
motor or cognitive impairment, nor does it potentiate the effects of 
alcohol. In formal clinical trials, buspirone was equi-effective and 6.2.2 anxiolytics and hypnotics
Fig. 6.2.2.1 Guidelines for withdrawal from benzodiazepines (BZ). (Reproduced 
with permission from J. Russell and M. Lader (eds.), Guidelines for the prevention 
and treatment of benzodiazepine dependence , Mental Health Foundation, 
London. Copyright 1993, Mental Health Foundation, London.)

SECTION 6  treatment methods in psychiatry 1182
equipotent to diazepam, but patients taking buspirone improve 
more slowly.(18) The side effects of buspirone include headache, 
dizziness, and nausea. Discontinuation is not accompanied by either rebound or withdrawal.
Other 5-HT
1A partial agonists have been developed mainly as 
potential antidepressants and antianxiety agents, but few have been marketed, mainly because of disappointing efﬁ  cacy.
Pregabalin
This compound is a structural analogue of GABA although it is not 
active at GABA receptors.(19) It binds with high afﬁ  nity to an auxil-
iary α2-δ subunit protein of voltage-gated calcium channels in the

iary α2-δ subunit protein of voltage-gated calcium channels in the 
CNS: it acts as a presynaptic modulator of the excessive release of neurotransmitters in hyperexcited neurones. It is predominantly excreted unchanged in the urine. It was initially developed for use as an adjunctive treatment in epilepsy and neuropathic pain. Several clinical trials in GAD have shown it to have efﬁ  cacy akin to 
those for benzodiazepines and venlafaxine.
(20) It has a rapid onset 
of action and was effective in preventing relapse over 34 weeks. T olerance was good during dosage escalation to the usual dose of 150–600 mg/day, mild dizziness and somnolence being the usual adverse effects. No clinically signiﬁ  cant withdrawal was seen after 
tapering. It is approved for the treatment of GAD in Europe, and is a signiﬁ  cant introduction.
Antiepileptic drugs
There is a long history of the use of many of these compounds in

There is a long history of the use of many of these compounds in 
anxiety disorders,(21) but they are not routine choices.

Phenothiazines, such as chlorpromazine and trifluoperazine, and a range of other antipsychotic drugs have been advocated for treating anxiety. The dosage recommended is quite low, typically less than half the initial antipsychotic dose used in psychotic patients. Sometimes, even at this dosage, the antipsychotic drug is not well tolerated by the anxious patient because unwanted autonomic effects, such as dry mouth and dizziness, too closely resemble the symptoms of anxiety. Even more unwelcome are extrapyramidal symptoms such as restlessness (mild akathisia) and parkinsonism, although at the low doses advocated such unwanted effects are uncommon. There may even be a risk of tardive dyskine-sia. The chief advantage of this medication is that dependence is virtually unknown, so the main indication for their use is in patients with histories of dependence on other central nervous system

depressant drugs such as alcohol or barbiturates.
Antidepressants
Several of these drugs, such as amitriptyline, doxepin, and 
trazodone, have useful secondary sedative properties. They are widely prescribed for depressed patients with anxiety or agitation. More recently, several SSRI antidepressants such as paroxetine and escitalopram have been evaluated in the treatment of various anxiety disorders. SSRIs are now the treatment of choice in chronic anxiety disorders.
(22, 23)
MAOIs have been used for many years to treat phobic states, but 
the well-known range of unwanted effects, including hypotension, limb oedema, and dietary and drug interactions, preclude their routine use.β-adrenoceptor antagonists
Beta-adrenoceptor antagonists may help patients with anxiety, but 
usually only those complaining of somatic symptoms. They are still favoured by some primary care doctors.
Antihistamines

The older compounds penetrate the brain readily and are quite sedative. Hydroxyzine has been evaluated in at least two placebo-controlled trials in doses of 50 mg/day: it proved to be signiﬁ  cantly 
better than placebo. The advantages are that paradoxical reactions are rare, cognitive function including memory is largely unaffected, and rebound and withdrawal seem rare.
Clinical effects of hypnotics
Insomnia is a common symptom,(24) especially in the elderly.(25)
Nonetheless, many complaints of insomnia are unfounded as the patient has unreal expectations concerning sleep. Elderly people fail to appreciate that it is normal to sleep less and less deeply as they age. Napping during the day also decreases the need for sleep at night. Some people can manage on 5 to 6 h a night indeﬁ  nitely,

and yet worry that this is insufﬁ  cient. Explanation and reassurance 
relieve their worries.
In many patients complaining of more severe insomnia, the c ause 
is a physical complaint such as pain, breathlessness, or pruritus. The treatment is for that of the primary complaint. In many other cases, the insomnia is either a symptom of psychiatric distress, anxiety, or depression, or it is iatrogenic, caused by the very drugs prescribed to relieve the insomnia. In the ﬁ  rst instance, treatment is directed 
towards the primary condition; in the second, a careful regimen of 
drug withdrawal, or substitution and subsequent withdrawal, should be instigated, as discussed earlier for anxiolytic medication. Some drugs, of which caffeine is the most common, induce insom nia. 
Alcohol may also disrupt sleep, particularly during the latter half of the night.
Despite this, a substantial number of patients cannot be placed

Despite this, a substantial number of patients cannot be placed 
into these categories and yet they persistently complain of insomnia (primary insomnia). Careful evaluation of the issues may yet reveal some relationship to stresses, both transient and persistent. It can be established that these patients are responding to unusual or pro-tracted pressures of life: a man worries over possible redundancy, his wife is concerned about their delinquent son, their daughter is lovelorn, and grandmother is anxious over her increasing frailness. Giving drugs may set in train a long-term process culminating in drug-related insomnia without solving the basic problems.
Short-term symptomatic relief is acceptable when the stress is

Short-term symptomatic relief is acceptable when the stress is 
undoubtedly severe but transient. Even so, the hypnotic agent must be chosen carefully. The elimination half-life is the most important consideration. Those with half-lives over 12 h, such as nitrazepam, are only appropriate where an anxiolytic effect is required during the day as well as sleep induction at night. Even here, diazepam 5 to 15 mg, one dose at night, may be preferred. T emazepam with its shorter half-life will encourage sleep onset without leaving the patient with too many residual sedative effects the next day. Unfortunately, it has been extensively abused.
The management of chronic insomnia is much more 
problematic.
(26) The newer compounds zopiclone and zolpidem 
are also short-acting agents and can help assure a good night’s

1183
sleep without much risk of residual sedative effects the next day.(27)
This is dependent on the dosage being kept modest, especially in 
the elderly. Eszopiclone is licensed in the United States for long-
term use in chronic insomnia and is already used extensively there.
Zolpidem and zaleplon can be used in a different strategic ways 
from other longer-acting drugs. Hypnotics are traditionally taken 
every night before going to bed to induce or maintain sleep. 
However, the severity of insomnia usually varies from night to 
night. Consequently, regular usage may be partly, or even largely, 
unnecessary, and increases the risk of habituation and dependence. 
Very-short-acting compounds are unlikely to leave residual effects 
the next day, even taken up to 5 h or so before the expected time of 
wakening. Consequently, the insomniac can refrain from regular 
hypnotic usage but, instead, wait up to an hour or so after going

hypnotic usage but, instead, wait up to an hour or so after going 
to bed to see if natural sleep supervenes before resorting to medica-
tion. This changes the regular prophylactic use of hypnotics to 
‘as needed’ , and lessens the risk of habituation and dependence. 
Furthermore, the patient is gratiﬁ  ed to feel that he or she has 
control of the medication instead of vice versa.
Residual effects
Residual effects can be a problem especially when long-acting drugs 
are used repeatedly. Dosage is important here, since residual effects 
increase in both magnitude and duration as the dose is increased. It 
should be remembered that hypnotics are the only class of drugs in 
which the main therapeutic effect (drowsiness) is identical with the 
main unwanted effect; the two are merely separated by 8 h in time. 
A short-acting hypnotic compound will be devoid of residual

A short-acting hypnotic compound will be devoid of residual 
effects the next day, but the patient may wake early. After taking a 
longer-acting compound, sleep may be prolonged but hangover 
effects pronounced.
Idiosyncratic effects
Adverse effects with triazolam alerted prescribers and regulators to 
possible major adverse effects of short-acting benzodiazepines. The 
adverse reactions in question include daytime anxiety, amnesic 
effects, and episodes, and morbid affects such as depression and 
hostility. In summary, the evidence suggests that these are class 
effects common to the benzodiazepines, although more likely to occur the shorter the duration of action of the drug and the higher 
the dose. Alcohol is also capable of producing these effects.
Rebound
Discontinuation of many hypnotics is often followed by worsening

Rebound
Discontinuation of many hypnotics is often followed by worsening 
of sleep compared with pretreatment levels. In practical terms, 
insomniac patients ﬁ  nd that their sleep is disturbed for a night or 
two after abrupt discontinuation of what appeared to be effective 
medication. Some of this rebound is subjective as patients taking 
sleeping pills tend to overestimate their sleeping time (compared 
with sleep laboratory recordings); on withdrawal, they underesti-
mate their sleep. The intensity of rebound insomnia is strongly 
related to dose but less clearly to the duration of use, and marked 
individual differences exist. The risk of rebound is greater with 
short-half-life compared with the long-half-life compounds. 
Tapering off medication lessens the likelihood of rebound. 
However, despite clinical impressions that rebound insomnia might 
lead to the resumption of medication, there is little evidence

lead to the resumption of medication, there is little evidence 
for this.(28)
Dependence may supervene on the longer-term use of hypnotics; 
giving a long-acting benzodiazepine drug only once in 24 h does 
not protect against such an eventuality. The management of the 
withdrawal syndrome that may occur is largely the same as with the 
anxiolytic benzodiazepines.
Abuse
A growing problem with these drugs is abuse—non-medical use, 
on a regular or sporadic basis, often in a polydrug context. 
Worldwide, ﬂ  unitrazepam is the main problem and can be taken 
orally, by injection, or by snifﬁ  ng. In the United Kingdom, temaze-
pam is widely abused by injection. The injected drug has a marked 
sedative and/or disinhibiting effect, resulting in chaotic behaviour, 
carelessness, and an enhanced risk of the transmission of commu-

nicable diseases such as HIV infection and hepatitis.
Other hypnotics
Gaboxadol is a GABA agonist. Preliminary data suggest useful 
hypnotic properties.
Melatonin preparations
A series of compounds are being developed based on melatonin. 
This hormone is important in the regulation of sleep and is secreted 
at night. Some elderly insomniacs seem to be deﬁ  cient in melatonin. 
Preparations include Circadin®, licensed in the UK for short-term 
use in insomnia in over 55s. Ramelteon is a melatonin1 and melato-
nin2 agonist. It is licensed in the United States for insomnia, and is 
effective in inducing sleep: it has a favourable safety proﬁ  le.(29)
In many countries the drug treatment of both anxiety and insom-
nia still largely revolves around the use of the benzodiazepines. 
Nevertheless, controversy and disagreement still rage about the

Nevertheless, controversy and disagreement still rage about the 
risk–beneﬁ  t ratio of compounds in this area. Short-term use in 
both indications is well established, with a favourable database as a 
Fig. 6.2.2.2 Table of half-lives.6.2.2 anxiolytics and hypnotics

SECTION 6  treatment methods in psychiatry 1184
rationale for this approach. However, long-term use is still only 
researched in a limited way. While both the efﬁ  cacy and safety of 
long-term use remain unclear, acceptance of current guidelines limiting the use of benzodiazepines seems wise.
The advent of the SSRIs as anxiolytics has driven a wedge between 
the treatment methods for anxiety and insomnia. Anxiety can be treated just as effectively with an SSRI (and probably, pregabalin) as with a benzodiazepine, and more safely. The treatment of insomnia still relies on the benzodiazepines until the risk–beneﬁ  t ratio of newer 
drugs such as the melatonin-related compounds becomes clear.
Nevertheless, in the author’s opinion the most important 
outstanding issue is the relationship between drug and non-drug treatments.
(30) The management of anxiety disorders and

(30) The management of anxiety disorders and 
of insomnia is complex and is hampered by a dearth of informa-tion concerning the relative merits of various treatment modalities. Much research is also needed on the optimum strategies for combining all the therapies available to us, and on identifying predictors of response.
Developments in the neuropharmacology of insomnia hold out 
the promise of new compounds with novel and perhaps more effective modes of action.
(31) With respect to anxiety disorders, a 
major shift of emphasis has followed the demonstration of the efﬁ cacy of the SSRIs.
(32)
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1185
6.2.3 Antidepressants
Major depressive disorder is a serious, recurrent illness which levies 
a crippling toll on individuals, families, and society in general. The importance of depression as a major public health problem is emphasized by ﬁ  ndings from the World Health Organization 
Global Burden of Disease survey in showing that in 1990 it was the fourth largest cause of burden of disease (i.e. years of life lost due either to premature mortality or to years lived with a disability). It has been estimated that by the year 2020 it is expected to be the second largest cause of burden of disease.
(1) Depression is under-

diagnosed and frequently under-treated, and depressed individuals have a much higher risk for suicide. The primary treatment for depression involves the use of antidepressant drugs, and it is there-fore important that clinicians become familiar with and adept in utilizing this important group of compounds. Although primarily used for the treatment of depression, drugs within this category also have a number of other important uses. A thorough under-standing of the pharmacology of antidepressants will aid the clini-cian in the selective use of these drugs for patients with depression as well as patients with a number of other disorders.
A brief history of antidepressant discovery 
and theories of action
Table 6.2.3.1 gives a brief chronology of antidepressant drug

Table 6.2.3.1 gives a brief chronology of antidepressant drug 
discoveries and theories of drug action. It is a comment on our understanding of the illness that some of the major advances in the pharmacotherapy of depression have been serendipitous. Prior to 1954, except for the use of electroconvulsive therapy, there were few effective drug treatments for depression. In 1954, the antidepressant era was initiated with the observation that some patients with 
tuberculosis displayed mood elevations following treatment with the antituberculosis agent iproniazid.(2) Following this initial ser-endipitous observation, the antidepressant effect of iproniazid was conﬁ  rmed(3) and its action of inhibiting monoamine oxidase was 
reported. Iproniazid had signiﬁ  cant toxicity and other monoamine

reported. Iproniazid had signiﬁ  cant toxicity and other monoamine 
oxidase inhibitors (MAOIs) were subsequently introduced. Independent from the work on MAOIs, imipramine, which has a chemical structure similar to the phenothiazines, was assessed as an agent to treat agitation in psychotic patients where it was found to be ineffective. However, it was noticed (again serendipitously) that imipramine produced an improvement of mood in the subset of patients who had symptoms of depression. Kuhn then reported in 1958 that imipramine was an effective antidepressant.(4)
One of the earliest theories of antidepressant drug action was 
that the antidepressant effect was produced by an increase of serot-onin (5-hydroxytryptamine ( 5-HT )) in brain. This was supported 
by an initial study showing that an MAOI plus tryptophan, the pre-cursor of 5-HT, was a more effective antidepressant treatment than an MAOI alone.
(5) Subsequently, the discovery that imipramine and

(5) Subsequently, the discovery that imipramine and 
desipramine had effects in inhibiting the reuptake of noradren aline 
(norepinephrine) and adrenaline (epinephrine) into the syna pse led 
to the catecholamine theory of depression, which proposed that antidepressant treatments act by increasing the level of cate-cholamines at brain synapses.
(6, 7) T en years later, it was reported 
that in laboratory animals most antidepressant treatments lead to downregulation of β-adrenergic receptors. This supported the pro-
posal that antidepressants act by reducing β-adrenergic receptor 
sensitivity.
(8) However, the reduction in β-adrenergic receptor 
sensitivity occurred within hours and antidepressant effect requires 1 to 3 weeks and futher not all effective antidepressant treatments produce reductions in β-adrenergic receptor sensitivity.
In the 1970s and 1980s, a large number of studies on antidepres-

sants were conducted in laboratory animals which demonstrated that they produced a number of changes in monoamine receptor sensitivity.
(9) In the late 1980s, a number of neurophysiological 
Table 6.2.3.1 History of discovery of antidepressants and pharmacological theories of antidepressant drug action
Year Discovery or theory Reference
1954 Discovery that MAOIs have antidepressant effects 2, 3
1958 Discovery that the tricyclic drug imipramine is an effective antidepressant 41963 Serotonin theory of depression:  MAOIs act by increasing serotonin and tryptamine in brain 5
1965 Catecholamine theory of depression:  ADTs act by increasing cathecolamines in brain 6, 7
1975 β-Adrenergic receptor theory of depression:  ADTs act by altering the sensitivity of several monoamine receptor subtypes in brain 8

1981 Monoamine receptor sensitivity theory of depression:  ADTs act by altering the sensitivity of several monoamine receptor subtypes in brain 9
1987 Serotonergic augmentation theory of depression:  ADTs act by decreasing sensitivity of presynaptic serotonergic autoreceptors and 
increasing sensitivity of serotonergic postsynaptic receptors to increase overall efﬁ  cacy in serotonergic transmission10
1996 A molecular and cellular theory of depression:  ADTs act by producing a sustained activation of the CAMP system which increases brain 
levels of neurotrophic factors that reverse the effects of stres in certain brain areas14
1998 Discovery that a substance P antagonist that does not interact with monoamine systems is as effective an antidepressant as an SSRI 
(paroxetine)16

2000/2006 Demonstration of antidepressant properties of ketamine implicating the glutamatergic system in the pathophysiology of depression 19, 20
ADT, antidepressant treatment.6.2.3 antidepressants

SECTION 6  treatment methods in psychiatry 1186
studies provided evidence that the delay in onset of antidepressant 
effects could be accounted for by a slow decrease in sensitivity at presynaptic serotonergic autoreceptors which has the overall result of increasing serotonergic function after days and weeks of treat-ment.
(10) An elaboration on the receptor sensitivity theory was the 
discovery that most antidepressants produce alterations in the sen-sitivity of a speciﬁ  c glycine-sensitive site on the N-methyl-d-aspar-
tate (NMDA) receptor.
(11) A subsequent study showed that an 
NMDA antagonist may have antidepressant actions(12)and this line

NMDA antagonist may have antidepressant actions(12)and this line 
of thought has borne fruit recently in a possible novel mechanism of action for antidepressant treatment. An additional receptor sen-sitivity change thought to be important in the mechanism of action of antidepressants involved changes in the sensitivity of receptors for glucocorticoids. It was found that antidepressants produce an overall improvement of inhibitory feedback on the hypothalamic-pituitary-adrenal axis
(13) and that speciﬁ  c corticotrophin releasing 
hormone (CRH) antagonists have antidepressant properties.(14)
A more recent theory of antidepressant drug action involves 
ﬁ ndings that antidepressant treatments affect intracellular path-
ways and neurotrophins. It was found that many antidepressants, in spite of β-adrenergic receptor downregulation, continue to pro-

duce sustained activation of the cAMP system and that this is related to increases of neurotrophic factors in brain.
(15)
Neurotrophins reverse the effects of stress in some brain areas and this raise the possibility that antidepressants act by increasing neu-rotrophins which reverse the effects of stress in important brain areas of depressed patients.
Throughout the 1980s, and 1990s a number of compounds that 
do not ﬁ  t the standard monoamine theories of depression have 
been found to be effective clinical antidepressants. One of these drugs, tianeptine, actually increases the uptake of 5-HT into nerve endings, an effect that is opposite to the standard selective serot-onin reuptake inhibitors ( SSRI s).
(16) Similarly, while there was

(16) Similarly, while there was 
intense interest in a report of possible antidepressant efﬁ  cacy of 
a substance P receptor antagonist,(17) which does not interact with 
monoamine systems, clinical trials for this speciﬁ  c compound were 
disappointing.
Although no single mechanism has been discovered that will 
account for the antidepressant effects of all effective antidepressant treatments, it is clear that initial effects on monoamine metabolism with subsequent effects of intracellular pathways is important. While clinical wisdom and data suggest that there is a lag of 7–21 days to antidepressant action, recent reports question this notion of delayed onset of efﬁ  cacy.
(18) Recently ketamine, an 
NMDA antagonist has been shown to have an onset of action much faster than that traditionally seen with conventional antidepres-sants
(19,20)  suggesting that the pursuit of novel mechanisms may

(19,20)  suggesting that the pursuit of novel mechanisms may 
indeed result in advances in the pharmacotherapy of depression. Using preclinical models, it has been suggested that both nonselec-tive NMDA antagonists as well as NR2B selective antagonists exert their antidepressant effects by regulating the functional interplay between AMPA and NMDA throughput.
(21)
Pharmacology and types of 
compounds available
Antidepressant drugs fall into a wide variety of chemical classes 
and they have a wide range of neuropharmacological effects. They are grouped in Tables 6.2.3.2, 6.2.3.3, and 6.2.3.4 based on the presumed primary action that leads to an antidepressant effect.

and they have a wide range of neuropharmacological effects. They are grouped in Tables 6.2.3.2, 6.2.3.3, and 6.2.3.4 based on the presumed primary action that leads to an antidepressant effect. 
Table 6.2.3.2 lists the drugs that inhibit the uptake of the monoam-ines noradrenaline, 5-HT, and dopamine into nerve endings which in turn is thought to increase the function of the respective monoamine systems in brain. Table 6.2.3.3 lists the drugs that inhibit monoamine oxidase and thereby increase the concentration of many amines in brain. Table 6.2.3.4 lists the drugs with other primary actions that do not primarily involve inhibition of monoamine uptake or monoamine oxidase inhibition.
In Table 6.2.3.2, the first 12 compounds are inhibitors of

In Table 6.2.3.2, the first 12 compounds are inhibitors of 
noradrenaline uptake with a variable potency of inhibiting 5-HT uptake. The drugs with secondary amine structures, desipramine, nortriptyline, protriptyline, amoxapine, and maprotiline are predominantly noradrenaline uptake inhibitors with little effect on 5-HT uptake.
(22) It can be seen in Table 6.2.3.2 that clomipramine, 
in addition to inhibiting noradrenaline uptake, is also a strong 5-HT uptake inhibitor. There are currently three selective serotonin and noradrenaline reuptake inhibitor (SNRI) drugs available; miln acipran (not licensed in the US), venlafaxine and duloxetine. Venlafaxine, inhibits both 5-HT and noradrenaline and 5-HT reuptake,
(23) as do milnacipran and duloxetine though in varying 
proportions. While afﬁ  nities vary depending on the system studied, 
milnacipran blocks 5-HT and norepinephrine reuptake with rela-tively equal afﬁ  nity, while duloxetine has been suggested to have a

milnacipran blocks 5-HT and norepinephrine reuptake with rela-tively equal afﬁ  nity, while duloxetine has been suggested to have a 
slightly greater selectivity for 5-HT and venlafaxine a much greater selectivity for 5-HT.
(24)Reboxetine (not licensed in the US) is a 
highly selective and potent inhibitor of noradrenaline reuptake.(25)
It has only a weak effect on the 5-HT reuptake and does not affect the uptake of dopamine.
A key issue in the pharmacology of all antidepressant drugs is the 
relative speciﬁ  city of their action. Drugs with a tertiary amine 
structure tend to produce more antagonism of α
1-adrenergic

1-adrenergic 
receptors which can produce hypotension, histamine receptors which can produce sedation, and muscarinic cholinergic receptors which can produce blurred vision, dry mouth, and urinary retention. This leads to more side-effects for these compounds than the drugs with a secondary amine structure. Venlafaxine has relatively less effect on these receptors and thus fewer side-effects
(23) (see 
Table 6.2.3.6).
SSRIs are probably the most widely prescribed antidepressants 
and represent a class of drugs that selectively inhibit 5-HT reuptake from the synapse. Unlike the tricyclics, they each have different chemical structures. The drugs listed in Table 6.2.3.2 have a rela-tively speciﬁ  c effect in inhibiting 5-HT uptake,
(22) and because of

(22) and because of 
their relatively speciﬁ  c effect on this monoamine system and the 
lack of antagonism of many other receptors, they have been found to have fewer side-effects. Escitalopram was introduced following the discovery that all of the inhibitory activity of citalopram on 5-HT reuptake resides in the S-(+)-enantiomer ( S-citalopram),
(26)
with S-citalopram being 167 times more potent than R-citalopram 
at inhibiting 5-HT reuptake into rat brain synaptosomes.
MAOIs are listed in Table 6.2.3.3. Two isozymes, monoamine 
oxidases A and B, are present in many discrete cell populations within the central nervous system, and glial cells also express monoamine oxidases A and B. The main substrates for monoam-ine oxidase A include adrenaline, noradrenaline, and 5-HT. The breakdown of dopamine in striatal regions of the brain is preferen-tially by monoamine oxidase B, but it can also be broken down by monoamine oxidase A. Since monoamine oxidase is located on the

1187
outside of the plasma membrane of the mitochondria in neurones, 
it is not able to eliminate amines that are stored inside vesicles. MAOI produces an increase in monoamines in the cytoplasm. It is thought that the increase in monoamine content is the primary mechanism of action of MAOIs, and other secondary changes including β-adrenergic receptor downregulation and other recep-
tor changes are secondary to the increased amine levels.
(27)
Four of the six drugs listed in Table 6.2.3.3 are irreversible inhib-
itors. The two reversible inhibitors are essentially inert substrate analogues, and there is usually a correlation between their plasma concentration and the reversible inhibition of monoamine

itors. The two reversible inhibitors are essentially inert substrate analogues, and there is usually a correlation between their plasma concentration and the reversible inhibition of monoamine 
oxidase A. Since isocarboxazid, phenelzine, and tranylcypromine are irreversible inhibitors of monoamine oxidases A and B, there can be serious side-effects when foods that are high in tyramine or other amines are ingested. In addition, these three drugs have strong interactions with other drugs that alter monoamine Table 6.2.3.2 Pharmacological actions of antidepressants: drugs that inhibit monoamine reuptake at the synapse
Drug Chemical class Relative reuptake inhibition
Noradrenaline 5-Hydroxytryptamine Dopamine
Imipramine Tricyclic ++ + 0
Desipraminea Tricyclic ++++ 00
AmitriptylineaTricyclic ++ + 0
Nortriptylinea Tricyclic +++ 0/+ 0
Trimipramine Tricyclic + 00
Clomipramine Tricyclic + +++ 0
ProtriptylineaTricyclic ++++ 00
Doxepin Tricyclic ++ 0/+ 0
Amoxapinea Tricyclic +++ 0 +

MaprotilineaTetracyclic +++ 00
Venlafaxine Bicyclic ++ + 0/+
Milnacipran SNRI +++ +++ 0/+
Duloxetine SNRI +++ ++ 0/+
Reboxetine NARI ++++ 0 +
Fluoxetine SSRI 0 +++ 0
Sertraline SSRI 0 ++++ +
Fluvoxamine SSRI 0 +++ 0
Paroxetine SSRI + ++++ 0
Citalopram SSRI 0 ++++ 0
Escitalopram SSRI 0 ++++ 0
0, None; 0/+, minimal; +, low; ++, moderate; +++, High; ++++, very high.
aSecondary amine.
Table 6.2.3.3 Pharmacological actions of antidepressants: drugs 
that inhibit monoamine oxidase
Drug Chemical class MAO A MAO B Reversible
Isocarboxazid Hydrazine Yes Yes No
Phenelzine Hydrazine Yes Yes NoTranylcypromine Amphetamine Yes Yes NoMoclobemide Morpholine Yes No YesBrofaromine Piperidine Yes No YesSelegiline Phenethylamine No Yes
a No
MAO, Monoamine oxidase.

a No
aSelective at lower doses; becomes non-selective at higher doses.Table 6.2.3.4 Pharmacological actions of antidepressants: drugs 
that do not act by strong inhibition of monoamine uptake or inhibition of monoamine oxidase
Drug Chemical class Possible pharmacological action
Trazodone Triazolopyridine Mixed 5-HT agonist/antagonist
Nefazodone Phenylpiperazine Mixed 5-HT agonist/antagonist, weak 
monoamine uptake inhibitor
Bupropion Unicyclic
amino ketoneWeak noradrenaline and dopamine 
uptake inhibitor
Mianserin Tetracyclic Antagonist α2-adrenergic auto- and 
heteroreceptors, increased 5-HT and 
noradrenaline release
Mirtazapine Tetracyclic Antagonist α2-adrenergic auto and 
heteroreceptors, increased 5-HT and noradrenaline release6.2.3 antidepressants

SECTION 6  treatment methods in psychiatry 1188
metabolism and therefore their use as antidepressants is much 
more limited than the tricyclics, SSRIs, or other antidepressant compounds. Tranylcypromine, which has a structure similar to amfetamine in addition to being an MAOI, is also thought to have a stimulant-type action of rapid onset. With the reversible MAOIs moclobemide and brofaromine, the recovery of monoamine oxidase back to normal levels after the drug is stopped is much shorter than with the irreversible MAOIs. These drugs increase concentrations of 5-HT, noradrenaline, and adrenaline that are short and parallel the time course of the monoamine oxidase A inhibition. These two drugs are more easily displaced by the pressor amines such as tyramine, and therefore, are thought to be safer than the irreversible inhibitors.
Selegiline, which has recently become available as a transdermal 
patch,
(28)is selective at lower doses for monoamine oxidase B but

patch,
(28)is selective at lower doses for monoamine oxidase B but 
at higher doses it becomes non-selective.(29) It has been primarily 
used for the treatment of Parkinson’s disease and the doses for treating depression need to be much higher (note: selegiline is not licensed in the UK for depression). Since monoamine oxidase B is not involved in the intestinal tyramine interaction, selegiline inter-actions with ingested monoamines have been minimal.
In addition to inhibiting monoamine oxidase, these compounds 
have other effects on monoamine systems that can produce side-effects. However, the major concerns are the interactions with dietary amines and other drugs that inﬂ  uence amine function. The 
combination of dietary interactions and slow recovery of monoam-ine oxidase following with the irreversible inhibitors makes these drugs one of the more difﬁ  cult treatments to administer. They are

combination of dietary interactions and slow recovery of monoam-ine oxidase following with the irreversible inhibitors makes these drugs one of the more difﬁ  cult treatments to administer. They are 
generally reserved for patients not otherwise responding to the 
other less toxic antidepressants.
In Table 6.2.3.4, compounds that are effective antidepressants 
but do not inhibit monoamine oxidase or have strong monoamine uptake inhibition are listed. Trazodone has shown receptor antago-nist activity at several 5-HT receptor subtypes although its active metabolite m-chlorophenylpiperazine (mCPP) is a potent direct 
serotonin agonist. It is a weak but relatively selective inhibitor of 5-HT reuptake, is an antagonist at 5-HT1A and 5-HT2 receptors in addition to its active metabolite mCPP being a potent 5-HT ago-nist.
(30)This leads to trazodone being classiﬁ  ed as a mixed 5-HT

(30)This leads to trazodone being classiﬁ  ed as a mixed 5-HT 
agonist/antagonist. It also has relatively weak 5-HT uptake inhibit-ing properties but with no effect on noradrenaline or dopamine uptake. Trazodone is virtually devoid of anticholingeric activity and therefore it has few side-effects in this area. However, it does produce considerable sedation and hypotension secondary to antagonism of α
1-adrenergic receptors and histamine receptors.
Nefazodone is an analogue of trazodone that was developed to 
overcome the orthostatic hypotension and sedation caused by the latter. Like trazodone it is a 5-HT receptor antagonist with weak monoamine uptake inhibition activity.
(31)It has less afﬁ  nity for the 
α-adrenergic receptors and is inactive on many other receptors. 
It too is metabolized to m-chlorophenylpiperazine which is an

It too is metabolized to m-chlorophenylpiperazine which is an 
active serotonergic agonist. Although the initial effects of nefazo-done involve alterations of 5-HT neurotransmission, these effects are complex and depend on the biological test used.
Bupropion resulted from focussed research to ﬁ  nd antidepressant 
compounds that would have fewer side-effects than traditional tri-cyclics (note: buproprion is  not licensed in the UK for depression). Bupropion is a mild inhibitor of noradrenaline uptake, has some effects on inhibiting dopamine uptake but has no effect on 5-HT uptake.
(32)These effects are not associated with β-adrenergic recep-
tor downregulation as is seen w ith many other antid epressants. One 
of the active metabolites is hydroxybupropion which also has an antidepressant proﬁ  le in laboratory animals. It is of interest that

of the active metabolites is hydroxybupropion which also has an antidepressant proﬁ  le in laboratory animals. It is of interest that 
bupropion is one of the few drugs that reduce REM latency since most other treatments increase it. Although the speciﬁ  c mecha-
nisms of bupropions antidepressant effects are not known, its unique proﬁ  le has led to its use in the treatment of bipolar disor-
der
(33) as well as its use in the treatment of smoking cessation.(34)
Mianserin and mirtazapine both have potent effects on antago-
nizing α2-adrenergic auto- and heteroreceptors.(35)They also 
antagonize other 5-HT receptors but have minimal effects on monoamine uptake or monoamine oxidase activity. Since α
2 recep-
tors inhibit noradrenaline release, their antagonism leads to an increase in noradrenaline release in many brain areas. In addition, antagonism of α
2-adrenergic heteroreceptors located on seroton-
ergic neurones results in an enhanced 5-HT release. With mirtaza-pine, since 5-HT

2 and 5-HT3 receptors are blocked, this could 
result in selective enhancement of 5-HT1-receptor-mediated 
neurotransmission. These drugs have low afﬁ  nity for muscarinic, 
cholinergic, and dopamine receptors and this is related to a reduced side-effect proﬁ  le. The combination of increased noradrenaline 
release and increased 5-HT release resulting from the α
2-antago-
nism on auto- and heteroreceptors is hypothesized to be the central mechanism of action.

2-antago-
Data on the pharmacokinetics of antidepressants are listed in Table 6.2.3.5. The tricyclic antidepressants are by and large well absorbed although time to peak plasma concentration can vary from 1 to 12 h depending on the drug and the individual. In gen-eral, these drugs are metabolized in the liver to a variety of metabo-lites, some of which are active. For instance, desipramine is a metabolite of imipramine and nortriptyline is a metabolite of amitriptyline. Most of these compounds have a long half-life (close to 24 h) that will allow for once-daily dosing. All the compounds are highly bound to plasma protein except for venlafaxine and milnacipran. Although many of the compounds have active metabolites, the exact percentage of each metabolite in patients and in their clinical effects is still largely unknown.

There is considerable individual variation in the metabolism of 
tricyclics, and a large component of this may be genetic. Up to 7 to 
9 per cent of the Caucasian population have been classiﬁ  ed as slow 
metabolizers (slow hydroxylators) which can be measured by the rate of hydroxylation of debrisoquin. The slow hydoxylation has been determined to be caused by a polymorphism in a cytochrome P-450 macrosomal enzyme (CYP2D6). It is of interest that many SSRIs are inhibitors of P-450 isoenzymes which can considerably inﬂ uence the metabolism of tricyclic antidepressants.
(36)In general, 
the increased renal clearance in children and a decreased renal clearance with age need to be taken into account with dosing.
The SSRIs are rapidly absorbed, although there is variability 
within the drug half-lives. The metabolism into active metabolites can vary the pharmacodynamic effects considerably. For example, ﬂ uoxetine is metabolized to norﬂ  uoxetine which has similar activ-

ity on 5-HT reuptake as ﬂ  uoxetine. The elimination half-life of 
norﬂ uoxetine is longer (4–16 days) than that of ﬂ  uoxetine (4–6 days). 
The desmethyl metabolite of sertraline although not nearly as

1189
potent as the parent compound, also has a much longer half life. 
The desmethyl metabolite of citalopram or escitalopram, although a potent noradrenaline uptake inhibitor, is much lower in concen-tration than citalopram and it weakly crosses the blood-brain barrier. Fluvoxamine, paroxetine, duloxetine or milnacipran do not have any active metabolites. The relatively long half-lives of some of the SSRIs, particularly ﬂ  uoxetine, require longer drug-free 
periods before switching to other classes of compounds especially before starting an MAOI.
The MAOIs are all rapidly absorbed. For the irreversible MAOIs, 
the elimination half-life and protein binding patterns are not as relevant because of the irreversible effects on monoamine oxidase. The reversible MAOIs have shorter half-lives and require multiple daily dosing.
(29)With the irreversible MAOIs, once the drug is

(29)With the irreversible MAOIs, once the drug is 
stopped, there needs to be time for new synthesis of monoamine oxidase. This requires a minimum of 5 to 7 days and the safest recommendation is to wait 2 weeks before starting other drugs that 
may interact with the MAOIs.
The five other antidepressants listed in Table 6.2.3.5 are 
rapidly absorbed but there is some variation in their elimination half-life. In general, the half-lives are short enough that multiple 
daily dosing is required. They are generally bound to plasma protein at a high level. The metabolites of trazodone and nefazo-done have mixed effects on 5-HT receptors which results in a complex overall effect. Trazodone and nefazodone undergo exten-sive hepatic metabolism and one major metabolite is m-chloroph-
enylpiperazine which stimulates 5-HT receptors. Many metabolites have biological activity with half-lives different to the parent compounds.
Bupropion is metabolized in the liver and its metabolites can be at

Bupropion is metabolized in the liver and its metabolites can be at 
higher concentration than the parent compound. The relationship between plasma bupropion and clinical response has been poor.
Table 6.2.3.5 Pharmacokinetics of antidepressants
Drug Absorption time to peak 
plasma concentration (h)Elimination half-life (h) Percentage plasma 
protein bindingImportant metabolite
Monoamine reuptake inhibitors
Imipramine 1.5–3 11–25 92 DesipramineDesipramine 3–6 11–31 90 2-OH-desipramine
Amitriptyline 1–5 10–26 94 Nortriptyline
Nortrityline 3–12 18–44 92 10-OH-nortriptyleneTrimipramine 3 9–11 95 NoneClomipramine 2–6 21–31 97 DesmethylclomipramineProtriptyline 6–12 67–89 93 NoneDoxepin 1–4 11–23 80 Desmethyldoxepin
Amoxapine 1–2 8–30 90 8-OH-amoxapine
Maprotiline 4–12 28–58 88 DesmethylmaprotilineVenlafaxine 2 5 30 O-desmethylvenlafaxineMilnacipran 0.5–4 8 13 NoneDuloxetine 6–10 8–17 95 None
Reboxetine 1.5–2.4 12–14 97 NA
SSRIs

SSRIs
Fluoxetine 4–8 24–120 94 Norﬂ  uoxetineSertraline 6–8 27 99 n-DesmethylsertralineFluvoxamine 2–8 15–26 77 NoneParoxetine 5–7 24–31 95 NoneCitalopram 1–6 33 80 NA (monodesmethylcitalopram)
Escitalopram 3–6 22–32 56 S-desmethylcitalopram
MAOIs
Isocarboxazid 3–5 NA NA NAPhenelzine 2–4 NA NA NATranylcypromine 1.5–3 1.5–3.5 NA NAMoclobemide 1–1.5 1.4 NA Numerous
Brofaromine 1–2 12–15 NA n-Desmethylbrofaromine
Selegiline 1–3 2–10 NA n-Desmethylselegiline
Other antidepressants
Trazodone 1–2 6–11 92 m-Chlor ophenylpiperazineNefazodone 1 2–4 99 m-ChlorophenylpiperazineBupropion 3 10–21 85 Bupropion threoamino alcoholMianserin 2–3 15–22 NA NA
Mirtazapine 2–3 20–40 85
None
NA, data not available6.2.3 antidepressants

SECTION 6  treatment methods in psychiatry 1190
Side-effects
The history of new drugs becoming available for the treatment of 
depression reﬂ  ects the efforts by the pharmaceutical industry to 
ﬁ nd compounds with reduced side-effects. This is in particularly 
important in the treatment of patients with medical illness because some of the side-effects can have considerable negative medical consequences. In Table 6.2.3.6, the propensity of the different drugs to produce some of the side-effects caused by antidepressants can be compared. The drugs that have high afﬁ  nity for the α
1-adrener-
gic receptors can produce hypotension. Antagonism of histamine receptors has been associated with sedation and there is a long list of anticholinergic effects associated with antagonism of muscarinic cholinergic receptors.
For the tricyclics, it can be seen that drugs with a tertiary amine

For the tricyclics, it can be seen that drugs with a tertiary amine 
structure produce increased sedation. There is also an increase in the frequency of side-effects associated with antagonism of mus-carinic cholinergic receptors such as dry mouth, constipation, blurred vision, urinary retention, dizziness, tachycardia, memory impairment, and at high and toxic doses, delirium. There is also an increased tendency for these same compounds to produce hypotension and to have unwanted cardiac effects that can lead to serious complications. In addition, the tertiary amines have a ten-dency to produce more weight gain than the secondary amines. The adverse effects have a particular impact on the tolerance of the patients to taking the medication. Most importantly the anticholin-ergic and cardiac effects can produce difﬁ  cult complications in the

elderly even leading to delirium when too high a dose is given. Amoxapine can cause extrapyramidal symptoms which are thought to be secondary to blocking dopamine receptors.
(37)The most 
common adverse effects in patients taking reboxetine during clini-cal trials were insomnia, sweating, constipation, dry mouth, and urinary hesitancy compared with placebo, and the rates of nausea, diarrhea, and somnolence were lower compared with ﬂ  uoxetine.
(38)
Nausea, dry mouth, dizziness, headache, somnolence, constipation, 
and fatigue were reported most frequently with duloxetine.(39)
The propensity to produce orthostatic hypotension is also a seri-
ous side-effect, particularly in the elderly. With the increased risk of falls and subsequent fractures in the elderly, this can be a serious health risk. A number of methods such as teaching patients to rise slowly from a supine position, tilting the bed upward, and maintenance of ﬂ  uid uptake could help prevent this. However,

other equally effective newer antidepressants produce much less of many of these side-effects, and they can be more safely used in the elderly.
Many of the drugs that are monoamine uptake inhibitors can 
cause cardiac conduction delays which may even lead to heart block in patients with pre-existing conditions. Severe overdose of these compounds can produce major and life-threatening cardiac arrhythmias. The secondary amines are generally thought to pro-
duce less cardiac effects than the tertiary amines. One of the char-
acteristics of the SSRIs which has led to their widespread use is their low rate of side-effects. The pharmacological speciﬁ  city of 
these compounds which bind to the 5-HT transporter, while not

these compounds which bind to the 5-HT transporter, while not 
binding to the other neurotransmitter receptor types, results in their producing a therapeutic effect without many of the unwanted side-effects. In placebo-controlled trials the incidence of early dis-continuation of SSRIs because of adverse events is intermediate between patients treated with placebo and patients treated with tricyclic antidepressants. Some of the symptoms reported with

these compounds include agitation, anxiety, headache, sleep dis-turbance, and tremor. One of the more troublesome side-effects is sexual dysfunction especially anorgasmia. Less frequently, there are changes in appetite with nausea, dry mouth, sweating, and weight change. In general, these effects are less than those observed with the non-SSRI monoamine uptake inhibitors. The interaction of SSRIs with MAOIs to produce the serotonin syndrome is discussed under toxic effects below. Fluoxetine and sertraline induced higher rates of sedation as dosages are increased but in contrast, paroxet-ine produces a dose-dependent increase in arousal.
In contrast with the fewer side-effects produced by SSRIs and

In contrast with the fewer side-effects produced by SSRIs and 
the other antidepressants that are not monoamine inhibitors, the MAOIs tend to produce frequent and often much more serious side-effects. Frequent side-effects include dizziness, headache, insomnia, dry mouth, blurred vision, nausea, constipation, forget-fulness, difﬁ  culty with urination, and weakness. There is also 
sexual dysfunction, including anorgasmia, impotence, delayed 
ejaculation, and decreased desire. Insomnia has also been reported. The original MAOIs iproniazid and isocarboxazid had a higher fre-quency of impairing liver function, but this is less with the other drugs. Pyridoxine deﬁ  ciency has been reported and should be 
considered in evaluating side-effects. The largest problem with the MAOIs is the interactions with foods and with other drugs. Food interaction is much less of a problem with the reversible MAOIs moclobemide and brofaromine.
(37–39)
Trazodone and nefazodone lack the anticholeringic side-

(37–39)
effects of many of the tricyclic drugs. This makes them useful compounds in many medical conditions where this effect would be problematic. Trazodone has an acute sedative effect which is useful in the treatment of agitation, anxiety, and insomnia. However, this can be a troublesome side-effect when the patient performs tasks that require full alertness. Trazodone appears to have more propensity to produce orthostatic hypotension than nefazodone, possibility related to the degree of α
receptor antagonism. Both trazodone and nefazodone, because of their lack of anticholinergic effects, have a low probability of producing difﬁ  culties in patients with cardiac illness. There 
is a slight tendency for weight gain but not nearly as strong as for some of the other antidepressants.
(40)A relatively rare but

(40)A relatively rare but 
important side-effect with trazodone is priapism. The risk for this side-effect is greatest during the early phase of treatment and the reporting of abnormal erectile function, including inappropriate or prolonged erections, should prompt quick discontinuation of trazodone treatment. Sexual side-effects have also been reported in women.
Bupropion has a very different side-effect profile than the 
conventional tricyclic antidepressants. It has no anticholinergic effects, is not sedating, and instead of weight gain, it suppresses appetite in some patients. In comparison to the SSRIs and trazodone and nefazodone, it also does not cause sexual dysfunction. There is no orthostatic hypotension, and bupropion does not produce cardiac side-effects. The possible stimulation of dopaminergic systems by bupropion can be related to its activating effects. This

may be useful in patients with retardation but may exacerbate 
patients with agitation and insomnia. Bupropion can make tics in attention-deﬁ  cit hyperactivity disorder and T ourette’s disorder 
worse.
(41)Patients have been described with bupropion-related

1191
psychosis which includes hallucinations and delusions. Psychotropic 
drugs also modulate seizure threshold and this needs to be carefully evaluated.
(42)For example, a serious side-effect of bupro-
pion that is rare but clinically important is the propensity to 
induce seizures in doses over 450 mg/day. Thus, bupropion should 
not be used at a dose higher than this and careful evaluation of history of seizures and other medical conditions or treatments that might lower seizure threshold should be evaluated in each patient.
Mianserin often produces drowsiness during the ﬁ  rst weeks of

Mianserin often produces drowsiness during the ﬁ  rst weeks of 
treatment but has much less anticholinergic side-effects than other tricyclic antidepressants. It has less effects on producing hypoten-sion and cardiac effects and there is only a low propensity for weight gain. Mirtazapine also has an increased amount of drowsiness and sedation. These side-effects are usually mild and transient. Mirtazapine has a low propensity to produce orthostatic hypotension or cardiac effects. There is a tendency for increased 
appetite and weight gain, however, which does not appear to be as severe as with tricyclics such as amitriptyline. Mianserin and mirtazapine have not been shown to produce high rates of sexual dysfunction as has been seen with trazodone and there is little evidence of lowering of the seizure threshold.
The side-effect proﬁ  les of the antidepressants are thought to

The side-effect proﬁ  les of the antidepressants are thought to 
relate to their respective effects on a variety of neurotransmitter systems. Clinicians should be aware of the proﬁ  le of side-effects for 
each of the antidepressants they prescribe. The dose and duration of treatment interact with the intensity and type of side-effect and should be considered relative to antidepressant effects when evalu-ating, switching or stopping treatment. Although all antidepressant treatments can provoke switches into mania in vulnerable patients with bipolar disorder, it would appear that the MAOIs have a somewhat higher propensity to do this than the other compounds. Table 6.2.3.6 Side-effects of antidepressants
Drug Sedation Anticholinergic effects Hypotension Cardiac effects Weight gain
Imipramine +++ ++ ++ +++ ++
Desipramine ++ + + + +
Amitriptyline +++ ++++ +++ +++ +++
Nortriptyline ++ + + + +
Trimipramine +++ +++ ++ +++ ++
Clomipramine ++ +++ ++ +++ +

Protriptyline 0/+ ++ + +++ +
Doxepin +++ ++ +++ ++ ++
Amoxapine + ++ + ++ +
Maprotiline ++ ++ ++ ++ +
Venlafaxine 0/+ 0/+ 0 + 0
Milnacipran 0/++ /++ 0/++ 0
Duloxetine ++ + 0/+ 0/++
Reboxetine 0 +/++ 0/+ 0/+ 0
SSRIs
Fluoxetine 0/+ 00 0 0
Sertraline 0 0 0 0 0
Fluvoxamine 0 0 0 0 0Paroxetine ++ 00 0
Citalopram ++ 0/+ 0/+ 0
Escitalopram ++ 0/+ 0/+ 0/+
MAOIs
Isocarboxazid + + +++ 0 +
Phenelzine + 0 +++ 0 ++
Tranylcypromine + 0 ++ 0 0/+
Moclobemide 0 0 0 0 0Brofaromine 0 0/+ 0/+ 00
Selegiline 0 0 + 00
Trazodone +++ 0 ++ 0/++
Nefazodone + 0 + 0/+ 0/+
Bupropion 0 0 0 + 0
Mianserin +++ 0/+ 0/++ +
Mirtazapine +++ + 0/++ +
0, None; 0/+, 0ccasional; +, law; ++, moderate; +++, veryhigh.6.2.3 antidepressants

SECTION 6  treatment methods in psychiatry 1192
It is important that the nature of somatic and behavioural symp-
toms be carefully recorded before the onset of treatment so that the emergence of side-effects can be documented for the individual patient.
Toxic effects
There is ongoing concern recently regarding the issue of antide-pressant use and suicide. The field has been grapplling with two inter-related issues: the possible risk of suicidal behaviour attributable to antidepressant treatment versus the potential decrease in suicidal behaviour afforded by antidepressant therapy. In 2004, there was an 18 per cent increase in adolescent suicides over the previous year.
(43)This coincided with increased publicity

(43)This coincided with increased publicity 
about the relationship between antidepressant treatment and sui-cide risk in children and adolescents and a subsequent decline in antidepressant prescriptions. The Food and Drug Administration (FDA) has issued a black box warning to warn the public about the increased risk of suicidal thoughts and behaviour (‘suicidality’) in children and adolescents being treated with antidepressant medications.
(44)
Often the most serious toxic effects are the result of overdose.

(44)
Often the most serious toxic effects are the result of overdose. 
Since depressed patients are at increased risk of suicide there is always the possibility that suicidally depressed patients will over-dose on their antidepressants. This is a very serious consideration and should be carefully evaluated when prescribing antidepressants. The symptoms and course of events following acute antidepressant overdose are complex and can be confusing unless a clear history of overdose is obtained. With tricyclic antidepressants, restlessness and excitement are initially seen with possible myoclonus, and dystonia and seizures leading to the development of coma. Seriously compromized patients can have depressed respiration with hypoxia, depressed reﬂ  exes, hypertension, and hypothermia. With 
the antidepressants that have antimuscarinic activity, there can be strong anticholinergic effects with mydriasis, ﬂ  ushed skin, dry 
membranes, and tachycardia.

Antidepressant overdose can be life-threatening and patients 
should receive immediate emergency medical evaluation. The local poison control centre should be contacted in any case of suspected antidepressant overdose. Appropriate follow-up can include the use of activated charcoal to absorb the drug as well as other medical supportive measures. Different compounds have different proba-bility of serious complications following an overdose and this is related to the amount ingested. However, drugs are often taken in combination, and it is difﬁ  cult to know the exact composition and 
amount of the overdose.
Another serious toxic side-effect is the interaction of MAOIs and

Another serious toxic side-effect is the interaction of MAOIs and 
foods that are high in tyramine and other monoamines. Tyramine has both direct and indirect sympathomimetic actions, has a pres-sor action, and is present in a number of foodstuffs. It is normally broken down by the MAO enzymes and in the presence of a MAOI will increase in concentration. Some of the foods that should be restricted in the diet of patients taking MAOIs are listed in Table 6.2.3.7. The reaction usually develops 20 min to 1 h following ingestion of food and is characterized by nausea, apprehension, occasional chills, sweating, r estlessness and hypotension with occipi-
tal headache, palpitations, and possibly vomiting. Neck stiffness, 
piloerection, dilated pupils, fever, and motor agitation are seen on examination. In severe forms, the reaction can lead to delirium, hyperpyrexia, cerebral hemorrhage, and death. The interaction of

piloerection, dilated pupils, fever, and motor agitation are seen on examination. In severe forms, the reaction can lead to delirium, hyperpyrexia, cerebral hemorrhage, and death. The interaction of 
the irreversible MAOIs with certain dietary components leading to the hypertensive reaction is one of the most serious drawbacks to the use of these types of compounds. The reversible MAOIs moclobemide and brofaromine have not been found to interact with tyramine in the same fashion as the irreversible MAOIs. Thus, they have much less liability in terms of producing the hyperten-sive crisis seen with the irreversible MAOIs.
(29)Phentolamine 
(5 mg) administered intravenously or nifedipine (onset of action 5 minutes), a calcium channel blocker, have been shown to be use-ful in the treatment of hypertensive reactions.
Serotonin syndrome is most often encountered when a MAOI 
is combined with an SSRI and there is an excess of 5-HT which overstimulates serotonin receptors.

(45)This syndrome can manifest

(45)This syndrome can manifest 
itself with sweating, diarrhoea, abdominal pain, fever, tachycardia, elevated blood pressure, myoclonus, hyper-reflexia, and with irritability and agitation. In its severe form, there can be severe hyperpyrexia, motor irritability, cardiovascular shock, and death. This toxic effect can result from the use of irreversible MAOIs and the addition of high amounts of tryptophan or other drugs that release serotonin in the brain. In addition, a common cause of this syndrome can result from the use of SSRIs and irreversible MAOIs concomitantly. Thus, it is strongly recommended that when MAOIs or SSRIs are utilized in sequence that the switch of treatment from one drug to the other has a minimum of a 14-day washout drug-free period before the second drug is started. In the case of discontinuing drugs with long half-lives such as ﬂ  uoxetine an

even longer period of up to 3 to 5 weeks may be necessary to safely avoid any possibility of producing the serotonin syndrome as a possible reaction to the drug combination.
The use of antidepressants during pregnancy is controversial 
and as always clinicians need to balance up the risks and beneﬁ  ts 
of treatments for individuals in this situation. Some recent studies have suggested that the use of SSRI medication in the perinatal period may be associated with adverse events like low birth weight and respiratory distress in the new born.
(46, 47) However, this 
needs to be balanced against the fact that women at risk for depres-sion may be at risk if not treated with antidepressants during pregnancy
(48)and both these risks need to be balanced against 
Table 6.2.3.7 Dietary restrictions for patients on MAOIs
Aged cheeses Liver Raisins
American cheesea Aged meats Soy Sauce
Cottage cheesea Canned meats Ripe avocado
Yogurta Processed meats Sauerkraut

Sour creama Meat extract Licorice
Wine Fermented foods Chocolatea
Beer Snails Coffeea
Yeast extract AnchoviesHerring Canned ﬁ  gsSardines Fava beans
a Not over 50g daily.

1193
The elderly are much more susceptible to toxic effects of antide-
pressants than younger individuals. In elderly patients, there may be other illnesses and the compensatory biological systems are not as resistant as in younger individuals. Mild toxic effects can be life threatening in the elderly. The newer antidepressants with fewer side-effects are the best drugs to use in the elderly.
There are a number of other toxic events that occur with less 
regularity. Isocarboxizid and phenelzine, since they are hydrazines, have some propensity to produce liver toxicity. Other much less frequent toxic events have occurred following antidepressants such as idiosyncratic individualized allergic reactions to the drug, suppression of the haematopoietic system, unusual dermatological reactions and hyponatremia.
(49)There are reports of death in 
children receiving desipramine(50) though the cause of these deaths

children receiving desipramine(50) though the cause of these deaths 
is unknown. Similarly, there is literature documenting increased incidence of gastric bleeding in association with SSRI treatment though there is a confounding effect of concomitant non-steroidal anti-inﬂ  ammatory medication.
(51)
Indications
Table 6.2.3.8 lists conditions where some antidepressant drugs have 
been found to be effective. Not all drugs are equally effective in each condition and very few clinical trials of the different com-pounds in each of the conditions have been conducted. Since the efﬁ  cacy of antidepressant drugs is in part related to the dose 
administered and/or blood levels, it is difﬁ  cult to be certain of the 
relative efficacy of one compound versus another when only single ﬁ  xed doses are used. The expense and difﬁ  culty of multidose

relative efficacy of one compound versus another when only single ﬁ  xed doses are used. The expense and difﬁ  culty of multidose 
designs in comparing two treatments are extremely large and this is the main factor limiting comparisons of different drugs across the conditions listed in Table 6.2.3.8. In addition, the large number of compounds available would make this a very dif-ﬁ cult task indeed. Another issue is that many of the drugs are 
only officially approved by the American Food and Drug Administration for use in depressed patients. Many of the indica-
tions listed in Table 6.2.3.8 are ‘off-label’ use of the medication.

tions listed in Table 6.2.3.8 are ‘off-label’ use of the medication. 
Since depression is the most prevalent illness, pharmaceutical com-panies have developed and brought forward drugs with depression as the primary indication. The expense of clinical trials to gain approval for other indications is high. Thus, for many of the condi-tions listed in Table 6.2.3.8, there is only fragmentary evidence for efﬁ cacy of some antidepressants and almost no data or comparable 
efﬁ cacy across drugs.
There are a number of different diagnostic approaches to

There are a number of different diagnostic approaches to 
depression as listed in Table 6.2.3.8. By and large, all of the drugs listed in Table 6.2.3.5 have been shown to be effective in the treat-ment of major depression. Most drugs have been studied in outpa-tient samples of patients with major depression. Their relative efﬁ cacy in the treatment of more severe conditions such as melan-
cholia, psychotic depression, or bipolar depression remains limited. In addition, the relative efﬁ  cacy of the different compounds as 
treatments for the depressive subtype, such as atypical depression, dysthymia, or secondary depression, has not been fully studied. There have been some reports that the MAOIs may be more effec-tive in atypical depression
(52) but not all studies have validated 
this. When depression in the elderly is under consideration, the side-effect proﬁ  le for each drug becomes a much more relevant

this. When depression in the elderly is under consideration, the side-effect proﬁ  le for each drug becomes a much more relevant 
consideration when choosing a speciﬁ  c drug.Anxiety disorders have considerable comorbidity with depression. 
Imipramine was initially found to be effective in the treatment of panic disorder and since then SSRIs have also been effective as well as MAOIs.
(53)Clomipramine was found to be effective in obses-
sive-compulsive disorder though more recently SSRIs tend to be favoured as they generally have fewer side-effects. Depending on the studies, both SSRIs and MAOIs have been effective treatments in social phobia as well as some tricyclic drugs. In general anxiety disorder and post-traumatic stress disorder, antidepressants have also shown efﬁ  cacy but not to the same extent as seen in panic 
disorder.
(54)
It is of interest that some antidepressants have been effective in

disorder.
(54)
It is of interest that some antidepressants have been effective in 
treating eating disorders. They are effective in bulimia nervosa(55)
but not in anorexia nervosa.(56)The dose of ﬂ  uoxetine to treat 
Table 6.2.3.8 Clinical indications for antidepressant treatments
Clinical condition
Major depression
MelancholiaPsychotic depression
Bipolar depression
Atypical depressionSecondary depression
Dysthymia
Depression in elderly (pseudodementia)
Prevention of depression relapse
Panic disorderObsessive–compulsive disorder
Social phobia
Generalized anxiety disorderPost-traumatic stress disorder
Bulimia nervosa
ObesityNausea with chemotherapy
Insomnia
NarcolepsySleep apnea
Pain
Migraine headache
Atypical facial painChronic pain syndromes
Diabetic neuropathy
Alcoholism
Smoking cessationBorderline personality disorder
Neurological disorders
EnuresisAttention-deﬁ  cit disorder

Premenstrual dysphoric disorder
Peptic ulcer
Urticaria pruritusPremature ejaculation6.2.3 antidepressants

SECTION 6  treatment methods in psychiatry 1194
bulimia nervosa is higher than the treatment of depression. The 
increase of weight seen following many antidepressants contrasts with some reports of the usefulness of SSRIs in the treatment of obesity.
In clinical practice, many clinicians have used trazodone as a 
night-time sedative. In the treatment of depression, sleep is one of the ﬁ  rst symptoms to show improvement following initiation 
of most antidepressant treatments. Various reports of use of anti-depressants in the treatment of narcolepsy and sleep apnoea have also been published.
Antidepressants have been effective in various pain syndromes.

Antidepressants have been effective in various pain syndromes. 
Since there is a wide range of the medical conditions producing pain, the results have been quite variable. In general the antidepres-sants have been able to reduce many of the painful symptoms as well as be effective in treating the secondary depression associated with chronic pain. However, they do not demonstrate the clear analgesic effect of drugs such as opioids.
Antidepressants have been reported to be effective in many other 
disorders including substance abuse, alcoholism, and smoking cessation.
(57) In children with enuresis a dose of imipramine as low 
as 25 mg has been seen to be safe and effective. In both children and adults, imipramine, desipramine, bupropion, and nortriptyline have been effective in the treatment of attention-deﬁ  cient disorder.
(58) 
Antidepressants have found use in the treatment of premenstrual 
disorders,(59)and they are also useful in the treatment of several 
neurological disorders.

(58) 
In general the indications and uses of a speciﬁ  c antidepressant 
in part depend on their side-effect proﬁ  le and on the previously 
demonstrated efﬁ  cacy. A major issue in the use of drugs to treat the 
large number of depressed patients with a comorbid medical con-dition is the careful choice of drug to minimize possible negative interactions with the medical disease.
Contraindications

The major contraindications in the use of antidepressants arise from the interaction of the pharmacological effects of antidepres-sant treatment with a comorbid condition of the patient or with diet or drug interactions. As mentioned above, the most serious contraindications arise from the use of irreversible MAOIs in patients taking other drugs or a diet that interacts and potentiates monoamine function resulting in a hypertensive crisis. A major contraindication is the use of MAOI in patients who receive anaesthesia.
(59) Patients on MAOIs should carry a card for medical

(59) Patients on MAOIs should carry a card for medical 
emergencies warning of drug interactions. Drugs that potentiate serotonin can interact with SSRIs to give the serotonin syndrome. The more relative contraindications involve the interaction of the side-effect proﬁ  le of the antidepressant treatment with either the 
primary medical disease or with other medications that the patient may be taking. Another relative contraindication is the use of antidepressants during pregnancy and breast feeding though clearly there needs to be a risk beneﬁ  t analysis of the use of the 
medication.
Many patients may be taking other medications and many are prescribed more than one psychotrophic drug at a time. Because of this, it is important that clinicians are aware of drug-drug interactions. Drugs that impair the cytochrome P-450 microsomal

enzyme system in the liver can interact with other drugs that are dependent on hepatic metabolism. For example, barbiturates and carbamazepine which induce hepatic enzymes can accelerate tricyclic metabolism and reduce steady state blood levels. Another anticonvulsant increasingly prescribed in the control of affective disorders, valproate, can reduce tricyclic drug clearance. Neuroleptics can elevate tricyclic blood levels which may be related to the impairment of the hydroxylation pathway for tricyclic metabolism. One of the more important drug-drug interactions 
involves the use of SSRIs and tricyclic drugs. This is related to 
the competitive inhibition of cytochrome by all of the SSRIs except ﬂ uvoxamine. This can result in clear elevations of steady state

the competitive inhibition of cytochrome by all of the SSRIs except ﬂ uvoxamine. This can result in clear elevations of steady state 
plasma concentrations. If combinations like this are utilized, the tricyclic doses need to be reduced. The utilization of a drug where plasma concentrations can be monitored (see Table 6.2.3.10) would help in the adjustment of dose if the tricyclic is combined with an SSRI.
One of the more serious drug-drug interactions previously 
mentioned is the interaction of tricyclic drugs with MAOIs. This can lead to hypertensive reactions and possibly stroke as well as possible induction of the serotonin syndrome.
(45)Often antide-

pressants are combined with phenothiazines. There is some evidence that chlorpromazine can block the metabolism of tricy-clics and thus when these two treatments are combined a possible reduction in the tricyclic treatment may be required. Other drugs that have been shown to increase tricyclic levels through blocking their metabolism include cimetidine, methylphenidate, and haloperidol. Tricyclic drugs can reduce the effects of clonidine and guanethidine in reducing blood pressure; an anticonvulsant, phenytoin, may be elevated; and the drug warfarin may be increased following tricyclic drugs. With the SSRIs, since there is a narrow pharmacological effect, interactions with anticholinergic agents or antihistaminics or alcohol are generally less than the tricyclics. The one major interaction is through the cytochrome P-450 family of enzymes which are inhibited by most SSRIs and interact with the metabolism of other drugs.

MAOIs. In addition to the dietary interactions, the MAOIs can interact with many of the ‘over-the-counter’ medications such as cough syrups and decongestants. Table 6.2.3.9 lists a number of compounds that have adverse drug interactions with MAOIs. Certainly many of the drugs that are direct or indirect adrenergic and dopaminergic agonists can produce overstimulation of the sympathetic nervous system. This can result in increased blood pressure and possibly adverse effects on the central nervous system. These drugs include all of the sympathomimetics, amphetamines, methylphenidate, and other stimulants. This can also occur with drugs such as other MAOIs and tricyclics or SSRIs that increase monoamine levels. MAOIs may worsen hypoglycaemia and require readjustment of the dosage of hypoglycaemic agents. Major con-cerns arise when patients on MAOIs need surgery because of the interaction with a number of compounds used in anaesthesia. This is more likely to occur with the use of

hypoglycaemic agents. Major con-cerns arise when patients on MAOIs need surgery because of the interaction with a number of compounds used in anaesthesia. This is more likely to occur with the use of pethidine. Careful considera-tion should be given to using a minimal 2-week washout for patients on MAOIs under going elective surgery.

The mixed 5-HT agonist drugs also have important drug-drug 
interactions. Trazodone can potentiate barbiturate and alcohol and it can increase drowsiness and sedation in patients taking these

1195
agents. It has also been reported to produce the serotonin syndrome 
at times when combined with an SSRI and possibly buspirone. Trazodone has altered the kinetics of benzodiazepines including alprazolam and triazolam. Trazodone interacts with cytochrome P-450 enzymes and has been shown to increase plasma levels of digoxin. Unlike trazodone, nefazodone does not appear to potentiate the sedative effects of alcohol.
Bupropion undergoes hepatic metabolism and its levels can be 
altered by other drugs effecting this metabolic route. There is some dopaminergic activation with bupropion and it has had adverse interactions with MAOIs. Because of the dopaminergic activity, there have been interactions with anti-parkinsonian medication. Because bupropion lowers the seizure threshold at higher dosages it can interact and with other medications that would have similar 
effects to produce seizures. A combination of bupropion and lithium

effects to produce seizures. A combination of bupropion and lithium 
may increase the likelihood of seizures. There are some reports that carbamazepine may decrease bupropion drug levels.
Mirtazapine is metabolized by cytochrome P-450 enzyme systems. 
There is the potential for interaction with other drugs via this system. The extent of use of mirtazapine is not as great as the older drugs and the drug-drug interactions are not as extensively reported.
In general, a large number of drug-drug interactions have been 
reported for the antidepressants. The drug-drug interactions can be quite variable depending on the patient and the dosage and duration of treatments. Thus, the adverse drug-drug interactions are one of the main reasons for the recommendations to use monotherapy rather than more than one drug. The use of drug combinations should, on average, be restricted to patients who have a poor response to a single treatment because of the possibility of adverse drug-drug interactions.

Drug withdrawal
Long-term administration of a drug can produce adaptive changes in many aspects of the human biology. When the drug is abruptly discontinued, ‘rebound’ drug withdrawal symptoms can be observed. This is most clearly seen with longer-term opiate, benzo-diazepine, or barbiturate use. Antidepressants are not addictive and dependence does not develop. With the antidepressants some degree of tolerance to the sedative and autonomic effects tends to develop and on abrupt withdrawal patients can have emerging 
symptoms consisting of malaise, dizziness, nausea, diarrhoea, chills, insomnia, restlessness, and muscle aches. Symptoms emerging dur-ing drug withdrawal have been seen following treatment with tri-cyclics as well as SSRIs.
(60)They have been described on occasion

(60)They have been described on occasion 
for MAOIs and the other non-monoamine uptake antidepressants. One main factor is the drug elimination half-life. Abrupt discon-tinuation of drugs with a short elimination half-life will produce more emergent side-effects than drugs with a long half-life. Thus, it has been found that patients taking shorter half-life drugs such as paroxetine and sertraline have more of an emergent symptom increase than patients taking the longer elimination half-life drug ﬂ uoxetine. Therefore, the dose of drugs with a shorter elimination 
half-life should generally be tapered over a 2- to 3-week period when being discontinued rather than being stopped abruptly. Drugs with a longer elimination half-life can be stopped abruptly since the parent drug and metabolite may last for many days. Clinicians must be aware that slow elimination means that parent drug and active metabolites remain in the body for up to several 
weeks.

weeks.
With the irreversible MAOI inhibitors, since there is a 1- or 
2-week period during with monoamine oxidase must recover following discontinuation of the MAOI, emergent side-effects have not been as regularly observed. In general with the other antide-pressants the withdrawal syndromes have not been permanent. Clinicians must make special efforts to discriminate between the return of symptoms and the emergence of new symptoms related to drug withdrawal.
Dosages and administration

In Table 6.2.3.10 some of the suggested optimal plasma concentra-tions for different antidepressant drugs are listed. For nortriptyline, desipramine, imipramine, and amitriptyline there is some evidence for a minimal plasma and concentration necessary for clinical response. An established therapeutic range is available for nortriptyline. Thus, patients with nortriptyline concentrations between 50 and 150 mg/ml seem to do much better. With the other drugs, it is generally thought that the plasma levels reﬂ  ect 
a minimal threshold of plasma concentration for clinical response. Below this level patients are less likely to respond and the upper limit indicates that there is increased possibility of the systemic or cardiac toxicity. Bupropion levels between 50 and 100 ng/ml may possibly be the best range. However, it is important that the dose be kept below 450 mg/day because of the possibility of seizures.

Except for nortriptyline and the use of plasma concentrations to 
obtain a minimal effective level, it is generally the patient’s clinical response that dictates dosage adjustments. One difﬁ  culty is that 
some patients with plasma concentrations outside the therapeutic range do respond and many patients with concentrations within the therapeutic range do not. Thus, the dosage needs to be adjusted depending on the individual patient’s response. Clearly plasma concentration monitoring can be helpful in many situations such as evaluating plasma levels when higher than standard doses are used, assessing toxicity, use in elderly patients or patients with comorbid conditions to evaluate possible drug interactions, or where compliance is questioned. Blood for drug levels is usually obtained for plasma levels during elimination phase which is usually in the morning 12 h after the last dose.Table 6.2.3.9 Adverse drug interactions with MAOIs
Other antidepressants Other MAOls

Buspirone CarbamazepineStimulants L-DopaSympathomimetics MethyldopaDopamine GuanethidineAmphetamines DextromethorphanMethylphenidate PethidineAdrenaline CocaineAsthma inhalants ReserpineDecongestants TryptophanAppetite suppressants Fenﬂ  uramine6.2.3 antidepressants

SECTION 6  treatment methods in psychiatry 1196
The authors would like to thank Aybala Saricicek MD for her assis-
tance in the preparation of the chapter.
Biological Psychiatry  (Elsevier)—the journal of the Society of Biological 
Psychiatry http://www.sobp.org/
Neuropsychopharmacology  (Nature Publishing group)—the journal of the 
American College of Neuropsychopharmacology http://www.acnp.org/
Schatzberg, A.F. and Nemeroff, C. B. (eds). (2004). American Psychiatric 
Publishing Textbook of Psychopharmacology (3rd edn.) American 
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Imipramine 25–75 (10) 150–300 (30–50) 200–300d

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6.2.4 Lithium and related 
mood stabilizers
Global categorization of the mood stabilizers
Lithium is the paradigmatic mood stabilizer. It is effective in the 
acute and prophylactic treatment of both mania and, to a lesser mag-nitude, depression. These characteristics are generally paralleled by the widely accepted anticonvulsant mood stabilizers valproate, car-

bamazepine (Table 6.2.4.1), and potentially by the less well studied putative mood stabilizers oxcarbazepine, zonisamide, and the dihydropyridine L-type calcium channel blocker nimodipine. In contrast, lamotrigine has a proﬁ  le of better antidepressant effects 
acutely and prophylactically than antimanic effects.
Differential responsivity among individual patients
Having grouped lithium, valproate, and carbamazepine together, it is important to note they have subtle differences in their therapeutic proﬁ  les and differential clinical predictors of response 
(Table 6.2.4.1). Response to one of these agents is not predictive 
of either a positive or negative response to the others.
(1,2) Thus, 
clinicians are left with only rough estimates and guesses about which drug may be preferentially effective in which patients. Only sequential clinical trials of agents either alone or in combination can verify responsivity in an individual patient.
(3)Individual 
response trumps FDA-approval .

Requirements for method of longitudinal assessment
Given this clinical conundrum, it is advisable that patients, family 
members, clinicians, or others carefully rate patients on a longitu-dinal scale in order to most carefully assess responses and side effects. These are available from the Depression Bipolar Support Alliance (DBSA), the STEP-BD NIMH Network, or www.bipolar-networknews.org and are highly recommended.
Increasing need for complex combination treatment
The importance of careful longitudinal documentation of symp-toms and side effects is highlighted by the increasing use of multi-ple drugs in combination.
(2)This is often required because patients 
may delay treatment-seeking until after many episodes, and very different patterns and frequencies of depressions, manias, mixed states, as well as multiple comorbidities may be present. Treating patients to the new accepted goal of remission  of their mood and

other anxillary symptoms usually requires use of several medica-tions. If each component of the regimen is kept below an individual’s side-effects threshold, judicious use of multiple agents can reduce rather than increase the overall side-effect burden.
Patients and family education is a must
There is increasing evidence of reliable abnormalities of biochem-istry, function, and anatomy in the brains of patients with bipolar disorder, and some of these are directly related to either duration of illness or number of episodes.
(4, 5) Therefore, as treatment resist-
ance to most therapeutic agents is related to number of prior 
episodes, and brain abnormalities may also increase as well, it 
behooves the patient to begin and sustain acute and long-term 
treatment as early as possible .
Early age of onset and treatment delay are related to an 
adverse outcome in adulthood
Despite the above academic, personal, and public health recom-

mendations, bipolar disorder often takes ten years or more to diag-nose and, hence, treat properly. In fact, a younger age  of onset is 
highly related to presence of a longer delay  from illness onset to 
ﬁ rst treatment, and  as well, to a poorer outcome  assessed both 
retrospectively and prospectively.
(6)

1199
BDNF: A role in vulnerability, onset, progression, 
New data indicate that the brain growth factor BDNF (brain-
derived neurotrophic factor) which is initially important to synap-togenesis and neural development, and later neuroplasticity and long-term memory in the adult is involved in all phases of bipolar disorder and its treatment.
(7)
It appears to be: 1) both a genetic (the val-66-val allele of BDNF) 
and environmental (low BDNF from childhood adversity) risk fac-
tor; 2) episode-related  (serum BDNF decreasing with each episode of 
depression or mania in proportion to symptom severity; 3) related to some substance abuse  comorbidity (BDNF increases in the VTA 
with defeat stress and cocaine self-administration); and 4) related to treatment .Lithium, valproate, and carbamazepine increase BDNF 
and quetiapine and ziprasidone block the decreases in hippocam-pal BDNF that occur with stress (as do antidepressants) .
More episodes convey more problems

A greater number of prior episodes is related to increased likeli-
hood of: 1) a rapid cycling course; 2) more severe depressive symp-toms; 3) more disability; 4) more cognitive dysfunction; and 5) even the incidence of late life dementia.
(4, 8, 9, 10)
Early effective treatment may protect the brain
Taken together, the new data suggest a new view not only of bipolar disorder, but its treatment. Adequate effective treatment may  not only (a) prevent affective episodes (with their accompanying risk 
of morbidity, dysfunction, and even death by suicide or the increased medical mortality associated with depression), but may also (b) reverse or prevent some of the biological abnormalities 
associated with the illness from progressing .
Thus, patients should be given timely information pertinent to

Thus, patients should be given timely information pertinent to 
their stage of illness and recovery that emphasizes not only the risk of treatments, but also their potential, ﬁ  guratively and literally, life-
saving beneﬁ  ts. Long-term treatment and education and targeted 
psychotherapies are critical to a good outcome.
Therapeutic strategy
We next highlight several attributes of each mood stabilizer, but recognize that the choice of each agent itself is based on inade-quate information from the literature, and sequencing of treat-ments and their combinations is currently more an art than an evidence-based science. We look forward to these informational and clinical trial deﬁ  cits being reduced in the near future and the 
development of single nucleotide polymorphism (SNP) and other neurobiological predictors of individual clinical response to individual drugs.
In the meantime, patients and clinicians must struggle with

In the meantime, patients and clinicians must struggle with 
treatment choice based on: 1) the most appropriate targetting of the predominant symptom picture with the most likely effective agent (Table 6.2.4.1 and 6.2.4.2) the best side-effects proﬁ  le for 
that patient (Table 6.2.4.2 and 6.2.4.3) using combinations of drugs with different therapeutic targets and mechanisms of action Table 6.2.4.1  Neuroprotective effects of lithium in cultured cells and animal models of diseases
I. Therapeutic Spectrum Lithium Carbamazepine Valproate Lamotrigine Nimodipine
A Acute Mania ++++ ++++ ++++ 0 (++)
B. Mania Prophylaxis ++++ +++ ++++ + (++)
C. Acute Depression ++ ++ ++ +++ (+)
D. Depression Prophylaxis ++++ ++++ +++ ++++ (++)
II. Correlates of Response
A.  Family History  + = 
positive – = negative+ Mania –Depression – Bipolar Disorder ND + Anxiety Disorder ND
B. Bipolar Type (BP) I II I,II I,II I,II,NOS
 Manic Type:   Pattern: Euphoric Intermittent Dysphoric Continuous Dysphoric

 Manic Type:   Pattern: Euphoric Intermittent Dysphoric Continuous Dysphoric 
Non-acceleratingContinuous Euphoric Ultradian
C. Comorbidities
 Anxiety Disorder None ++ +++ +++ (+)
 Substance Use None ++ +++ + /– ( +)
D. PTSD Utility 0 ++ ++ ++ 0
E. Other Unique Targets M-D-I vs.  D-M-I 
Antisuicidal AntimedicalMortalityAlcohol Withdrawal
Tigeminal NeuralgiaAlcohol Abstinence
Migraine Prophylaxis(Alzheimer’s Dementia)
(Migraine Prophylaxis) Subarachnoid Hemorrhage
F. Baseline PET Activity ? Hyper- metabolism ?  Hypo-metabolism Hypo-metabolismG. CSF SRIF (Somatostatin)
  Predicts Response: ? No Prediction ? ? Low SRIF
  Effect of Drug: ? Decreases SRIF Increases SRIF
III. Neurotropic Effects
A. Increase BDNF Yes Yes Yes ? ?
B. Increase Neurogenesis Yes ? Yes ? ?C. Neuroprotective Yes Yes Yes Yes (Yes)

Effect of Drug: ? Decreases SRIF Increases SRIF
Legend: ++++ = very marked; +++ = marked; ++ = moderate; + = mild or some effect; +/– = equivocal; () = ambiguous data; 0 = no effect; – = worse.6.2.4 lithium and related mood stabilizers

SECTION 6  treatment methods in psychiatry 1200
(Table 6.2.4.3 and 6.2.4.4) careful consideration of potential advan-
tageous pharmacodynamic interactions and disadvantageous phar-macokinetic drug-drug interactions that need to be avoided or anticipated.
Mood stabilizers
Lithium
In the late 1960s and early 1970s, open and double-blind randomized treatment and discontinuation studies revealed highly signiﬁ  cant effects of lithium in long-term prophylaxis .
These studies followed shortly after a series of studies demonstrat-ing lithium’s acute antimanic effects in comparison with both placebo and the existing neuroleptic treatments. High rates of response were touted and lithium clinics were established with the hope that the 60 to 80 per cent response rates revealed in the controlled clinical trials would be mirrored by clinical practice.
(11)
However, over the past two decades there has been increasing

(11)
However, over the past two decades there has been increasing 
recognition of the inadequacy of lithium both in acute treatment and long-term prophylaxis, even when used with adjunctive treat-ments such as antipsychotics, benzodiazepines, and antidepres-sants.
(12, 13, 14) Given this increasing cognizance of lithium’s less 
than dramatic efﬁ  cacy in many patients with bipolar illness, alter-
native and adjunctive treatments were sought.The anticonvulsants carbamazepine, valproate, and 
lamotrigine
Carbamazepine and valproate are now well recognized as potential 
mood-stabilizing anticonvulsants, and initial promising data are emerging for lamotrigine as well. The data are more equivocal for oxcarbazepine and minimal for zonisamide. Importantly, the 
GABA-active anticonvulsants gabapentin, tiagabine, and topira-mate  are not effective in acute mania  and thus cannot be consid-

ered mood stabilizers. Nonetheless, topiramate may be useful in some common comorbidities of bipolar illness including alcohol and cocaine abuse, bulimia, overweight, migraine, and PTSD. Similarly, gabapentin (which increases brain GABA and acts at the alpha
2 delta subunit of the L-type calcium channel) and its 
close relative pregabalin may have secondary utility in comorbid panic anxiety and social phobia, sleep disorder, alcohol withdrawal, and chronic pain syndromes.
L-type calcium-channel blockers
The dihydropyridine L-type calcium channel blockers became a focus of possible interest for lithium-intolerant and lithium-unresponsive patients based on a variety of clinical and theoretical rationales. Dubovsky et al .
(15) found increased intracellular 
calcium in blood elements of patients with bipolar illness, a ﬁ  nding

calcium in blood elements of patients with bipolar illness, a ﬁ  nding 
that has been replicated more than a dozen times. Dubovsky et al.(16)
proceeded to demonstrate the potential antimanic efﬁ  cacy of 
the L-type calcium channel blocker verapamil. Many other small Table 6.2.4.3  Global assessment of relative side-effects
Li CBZ VPA LTG NIMOD
Weight Gain ++ + ++ 00
Tremor ++ + /−+ + + /− 0
GI Upset ++ + ++ + /− 0
Memory Disturbance ++ + + −
Rash 0a++ + /−+ + 0
↓WBC ⎯+ + 00 0
Agranulocytosis 0 + 00 0
↓Platelets − 0b++ 00
↑ Liver Enzymes 0 ++ ++ (+) 0
Hepatitis 0 ++ ?0
Dizziness Ataxia Diplopia +/−+ + ++ + /−
Hyponatremia −+ + 00 0
Alopecia +/− 0 ++ ?0
Thyroid Decrements ++ + /−+ /−+ /− 0
Teratogenic ++ + + + 00
Malformations Epstein’s 
AnomalySpina 
Biﬁ  daSpina 
Biﬁ  da
Developmental Delay 0 +/−+ + + /− 0
Legend: a = psoriasis; b =with aplastic anemia; ++ = moderate to substantial or common;

Biﬁ  da
Legend: a = psoriasis; b =with aplastic anemia; ++ = moderate to substantial or common; 
+ = mild to less frequent; +/− = equivocal or rare; 0 = not present or no change; 
− = opposite effect; () = ambiguous ﬁ  ndingsTable 6.2.4.2  Global putative mechanisms of action
Antiglutamineric: +++ + ?
Via:Glutamate Uptake + 
Sodium Blockade + (+) +
↑ Brain GABA ++ /−+ + ⎯ 0
↑ GABA-B R in hippocampus (with 
chronic administration)+++
↓ Calcium Inﬂ  ux +++ + + +
Via: 
Weak NMDA Receptor Inhibition +++ + 0
Inhibition of Calcium-Channel Type ⎯ (L) T (N,P) L
↓ DA Turnover +++
Second Messenger System
↓ c-AMP , G proteins ++ ++ ⎯ ⎯ ⎯
PI Turnover ↓ (↑) N.C. ? +/−
PKC Inhibition ++ ++
↓ ras, MEK, Erk Pathway ++ ++
↓ Inositol Transport +++ ??
↑ BDNF +++
↑ Bcl-2 + +
Histone Deacetylase Inhibition ⎯+ + + ??

1201
controlled studies were also positive, although less than dramatic 
results have recently been reported by two groups.(17, 18) In addi-
tion, one controlled study found that verapamil was not an effective acute antidepressant, even though it appeared to have good antimanic properties.
(19)Verapamil was never widely used in 
clinical practice.
Given these ambiguities with verapamil, Pazzaglia et al.(20) and 
Post et al.(21) at the NIMH in the U.S. chose to explore the potential 
antimanic and antidepressant effects of the dihydropyridine L-type calcium channel blocker nimodipine which has a very different biophysical and pharmacological proﬁ  le from verapamil.
(22) In 
contrast to the phenylalkylamine verapamil, the dihydropyridine nimodipine is a more potent anticonvulsant that blocks cocaine-induced hyperactivity, sensitization, and dopamine overﬂ  ow; is 
positive in animal models of depression; and it improves rather than impairs cognition.
Pharmacology
Lithium

Lithium
A series of sequential decade-related candidate mechanisms for lithium’s psychotropic (mood-stabilizing) actions have been suggested over the last 50 years. These included:
◆ Effects on enzymes and biosynthetic aminergic neurotransmitter 
pathways (1950s)
◆ Effects on presynaptic adrenergic release and reuptake mecha-
nisms (1960s)
◆ Effects on postsynaptic receptor modulation and impact on 
receptor supersensitivity (1970s)
◆ Effects on second messenger systems, adenylate cyclase and 
G-proteins (1980s)(23)
◆ Effects on phosphoinositol turnover, protein kinases (PKC and 
GSK-36), and other signal transduction pathways (1990s)(24, 25)
◆ Most recently, effects on the nuclear level of DNA binding and 
gene transcription have been found that increase neurotrophic and other factors regulating neuroprotection versus apoptosis and cell death (2000s)
(26, 27)

(26, 27)
Several of these candidate mechanisms are summarized in 
Figs 6.2.4.1 and 6.2.4.2, and are compared with the mechanisms of some of the other mood-stabilizing anticonvulsants such as carbamazepine and valproate. Lithium’s effects on G proteins
(20) are 
conceptually intriguing in relation to lithium’s ability to modulate overactive systems, and preliminary support for its adenylate cyclase effects being important for acute mania are based on the ﬁ nding that novel adenylate cyclase inhibitors are also effective 
in acute mania.
(21) Similarly, recent studies implicating the ability 
of lithium and valproate to inhibit protein kinase C has been 
preliminarily vali dated with the demonstration of antimanic effects 
of the protein kinase C inhibitor tamoxifen in two double-blind studies.
(28, 29)

(28, 29)
Most recently, lithium has emerged as a possible neurotrophic 
and neuroprotective drug  via multiple potential pathways. 
It inhibits calcium inﬂ  ux through the N-methyl-D-aspartate gluta-
mate receptor;(23) it inhibits GSK-3B; and it increases the ratio of 
neurotrophic to cell death factors. For example, it increases Bcl-2 and brain-derived neuotrophic factor (BDNF) while decreasing the apoptotic factor BAX and P-53.
(25, 26)  Much work remains 
to be done to implicate or rule out these changes in the wide array of psychotrophic actions of lithium. Lithium also increases white blood cell count and platelets by increasing granulocyte-macrophage colony-stimulating factor.
(30) This effect is 
sufﬁ cient to overcome the benign white count suppression of 
carbamazepine.(31, 32)

The potential clinical relevance of this ﬁ  nding is also evidenced 
by the data that pretreatment with lithium can decrease the size of a cerebral infarct following middle cerebral artery ligation and decrease the amount of neurological deﬁ  cit.
(33)Given the new 
ﬁ ndings of altered size of crucial structures involved in emotion 
regulation in the affective disorders, including amygdale,(34, 35) 
hippocampus,(36) and prefrontal cortex,(4) one can only wonder 
whether lithium’s neuroprotective effects could alter some of these putative neuronal- or glial-based deﬁ  cits in central nervous system 
structure and function. The preliminary evidence supports this proposition because lithium increases patients’ NAA, a marker of neuronal integrity and, grey matter volume as well.
(37, 38)
Carbamazepine, valproate, and lamotrigine

(37, 38)
As seen in Table 6.2.4.2, since lithium, carbamazepine, and val-proate share a group of effects in common, one wonders if they are related to their global antimanic/antidepressant effects. Notable dif-ferences among these agents are also present, perhaps also related to some of the differences in therapeutic targets and comorbidities seen in Table 6.2.4.1.
Given the shared effects of carbamazepine and lamotrigine in 
potent sodium channel blockade and subsequent decreased release of glutamate, one wonders about mechanisms that account for their difference in the epilepsies (carbamazepine exacerbates while lamotrigine improves absence seizures) and bipolar disorder (lamotrigine is a better antidepressant than antimanic). Potential candidates are the effects on different calcium channel subtypes (N,P) and ability to inhibit GABA release, but factors critical to 
lamotrigine’s antidepressant effects remain to be elucidated.
(39)

(39)
L-type calcium channel blockers
There are several subtypes of voltage-dependent blockers of 
calcium inﬂ  ux which modulate the L-type channel, i.e. one with 
relatively long (L) opening times. These subtypes include the wide-ly recognized phenylalkylamines typiﬁ  ed by verapamil, the benzo-
diazepines typiﬁ  ed by diltiazem, the diphenylpiperazines typiﬁ  ed by 
ﬂ unarizine, and the 1,4-dihydropyridines typiﬁ  ed by nifedipine, 
nimodipine, isradipine, amlodipine, nicardipine, and nitrendipine. Remarkably, even though these agents all potently bind to this voltage-dependent calcium channel and act to inhibit calcium inﬂ ux, their biochemical and physiological effects are very different, 
as noted above.
Verapamil and the phenylalkylamines are charged and bind at 
the outer portion of the calcium channel, while the dihydropyrid-ines, which are uncharged (except amlodipine), bind deeper inside

the outer portion of the calcium channel, while the dihydropyrid-ines, which are uncharged (except amlodipine), bind deeper inside 
the calcium channel. These different membrane properties and 
binding characteristics result in a different proﬁ  le of effects for the 
dihydropyridines compared with the phenylalkylamines, including increased lipid solubility. It is possible that these differences relate to the increased effectiveness of the dihydropyridines on depres-sion
(40) and ultra rapid cycling seen in a small subgroup of lithium-
refractory bipolar patients.6.2.4 lithium and related mood stabilizers

SECTION 6  treatment methods in psychiatry 1202
Pharmacokinetics, dosage, and 
Lithium
Lithium blood levels are conventionally described as being thera-
peutic from 0.5 to 1.2 mmol/l. Within this range, there is a wide 
agreement that higher doses are associated with increasing num-
bers of side-effects, but there is disagreement as to whether this 
is uniformly accompanied by a better therapeutic effect. Gelenberg 
et al .(12) reported that higher doses of lithium in the 0.8 to 
1.0 mmol/l range averaging 0.83 mmol/l were 2.6 times as effective 
as doses achieving blood levels in the lower therapeutic range of 
0.4 to 0.6, averaging 0.54 mmol/l. This increased efﬁ  cacy  (i.e. lower 
risk of relapse) was achieved at the cost of a greater frequency of 
side effects . Three times as many patients given doses in the high 
range withdrew from the study due to side effects. A series of other 
studies suggest that low to moderate doses of lithium may be just as

studies suggest that low to moderate doses of lithium may be just as 
effective as those in the higher range.(13)
Data of Kleindeinst et al.(41) further suggest a differential dose/
effect relationship for lithium in mania versus depression prophy-
laxis. They found higher doses/blood levels more effective in pre-
venting manic episodes while, paradoxically, lower doses/levels 
were more effective in preventing depressions . There is a consid-
erable time lag before lithium reaches steady-state levels and some attempts at lithium loading with large doses from the outset have 
not been successful. A certain amount of time is needed for lithium 
to gain access into the central nervous system compartment and 
steady-state levels are not typically achieved until ﬁ  ve half-lives or 
approximately six days. With the advent of magnetic resonance 
spectroscopy it has been found that lithium levels in the brain are

spectroscopy it has been found that lithium levels in the brain are 
half those in serum and, based on one small study, may be better 
correlated with the degree of clinical response than serum levels. 
Older individuals have higher intracellular lithium levels , which 
may account for the observations of toxicity at apparently thera-
peutic blood levels .
While lithium has traditionally been administered in two, three, 
or four times daily dosing regimens in attempts to achieve the most 
consistent and stable blood levels possible, several ﬁ  ndings have led 
to changes in this pattern of dosing. Extended-release preparations 
are now available and suitable for twice-daily dosing. Even with the 
original preparations of lithium carbonate many clinicians and 
investigators have administered lithium in single nighttime doses 
in order to achieve the highest blood levels (and the potential for

in order to achieve the highest blood levels (and the potential for 
side effects) during sleep, and utilize the much lower trough levels at 
a time when the kidney, for example, can be relatively spared from 
continuously high lithium levels. Some investigators feel that this 
might be associated with lower long-term renal side effects, and pre-
liminary data suggest that this paradigm may not be associated with 
any loss of clinical efﬁ  cacy. Given lithium’s unique anti-suicide 
Fig. 6.2.4.1 Common and differential mechanism of mood stabilizers: Pl, phosphoinositol; AC, adenylate  cyclase; IMPase, 
inosital monophosphatase; PLC, phospholipase C; cAMP , cyclic adenosine monophosphate; NPY, neuropeptide Y; ACH, 
acetylcholine; G αs, G protein alpha (s) subunit; DA, dopaminergic; Ne, noradrenergic; PKC, protein kinase C; A1R, adenosine

acetylcholine; G αs, G protein alpha (s) subunit; DA, dopaminergic; Ne, noradrenergic; PKC, protein kinase C; A1R, adenosine 
A1 receptors; T4, thyroxine; Gap 43, growth-associated protein 43; CRE, cyclic response element; CBZ, carbamazepine; TRH, 
throtrophin-releasing hormone; CREB, cyclic response element binding protein; VPA, valproate; SRIF, somatosatin; t.o., turnover .

1203
effects and strong evidence of neurotrophic and neuroprotective 
effects in animals at clinically relevant blood levels of 0.5 mmol/l, 
administering lithium at whatever doses/blood levels are not associ-
ated with side effects would appear to have considerable merit .
Carbamazepine, valproate, lamotrigine
Carbamazepine , in contrast to oxcarbazepine, is a potent inducer 
of CYP 3A4  hepatic enzymes, accounting for auto-induction 
after one to three weeks of treatment.(8) With immediate release 
preparations, B.I.D or T.I.D. dosing is required, but with long-
acting preparations such as Equetro®(T egretol Retard®), all H.S. 
dosing should be considered. The dose and blood level to side-
effects relationships are highly variable and individual. In non-
emergency situations, 200 mg H.S. may be considered as a starting 
dose with slow upward titration to avoid or accommodate to side 
effects. In manic inpat ients initial dosing of 600 mg to 800 mg on 
day one may be tolerated.

While blood levels of 4–12 μg/ml are touted as therapeutic in 
epilepsy, there is no relation of blood level to degree of clinical 
response across either seizure disorder or affectively ill patients. 
Therefore, individualized titration to good clinical effect and 
minimal side-effects  burden is more appropriate than compulsive 
blood level monitoring.
Valproate may be given in loading doses of 10 to 15 mg/kg. 
Efﬁ cacy is usually observed between 50–120 mg/ml with a target of 
80 mg/ml or more in mania. Single nighttime doses can be employed
with both immediate release and extended release preparations, 
which may be better tolerated.
Lamotrigine must be dosed and titrated very slowly  in an attempt

Lamotrigine must be dosed and titrated very slowly  in an attempt 
to avoid the occurrence of a serious rash . A typical procedure is to start with 25 mg/day for two weeks and then 50 mg/day for two 
weeks, and then increase by 25 mg (preferably) to 50 mg/week 
thereafter. A target dose is about 200 mg/day, but increases 
to 400 mg/day in those showing partial responses is often tolerated. 
The rate of titration and target dose of lamotrigine should be 
halved on valproate  (which doubles lamotrigine levels ) and can be 
doubled on carbamazepine and related potent enzyme inducers.
The pharmacokinetics of the dihydropyridine L-type calcium chan-
nel blockers differ markedly. Nimodipine has a T½ of 1–2 h requir-
ing T.I.D. dosing to peak total doses of 240 to 480 mg/day. 
Isradipine’s T½ is 8 h, allowing B.I.D. dosing to a peak dose

Isradipine’s T½ is 8 h, allowing B.I.D. dosing to a peak dose 
of 15 mg/day. Notably, amlodipine has a longer half-life and is suit-
able for single nighttime or twice-daily dosing in comparison with 
the better psychiatrically studied drugs nimodipine and isradipine. 
However, as long-acting preparations of these compounds become 
available, the importance of this half-life dissociation among the 
different compounds may dissipate. In our patient cohort at the 
NIMH, the pharmacokinetics of nimodipine (Bay e 9736) and its 
several metabolites (Bay o 1762, Bay m 5397, and Bay m 8922) 
were characterized by a rapid peaking (in 30–45 min) and decline 
in the second hour in response to a 60 mg challenge dose at 
steady-state blood levels after an overnight fast. Additional small 
secondary peaks occurred when usual dosing of four-times-a-day

secondary peaks occurred when usual dosing of four-times-a-day 
was resumed. There were no notable differences between capsule 
and tablet preparations. The phenylalkylamine verapamil has a 
5–8 h half-life, also requiring T.I.D. dosing to a target peak 
daily dose of 480 mg/day.Fig. 6.2.4.2 Mechanisms of mood Stabilization. Depicted schematically at the top of the ﬁ  gure is a synapse with various 
types of channels, neurotransmitters, and proteins associated with the mechanisms of action of the mood stabilizers listed in 
the table below. Row headings : Li, lithium; CBZ, carbamazepine; VPA, valproate; LTG, lamotrigine; GPN, gabapentin; 
TPM, topiramate. Column headings ; K+ efﬂ  ux; Na+ inﬂ  ux; EAA, excitatory amino acids; GABA, γ-aminobutyric acid;

TPM, topiramate. Column headings ; K+ efﬂ  ux; Na+ inﬂ  ux; EAA, excitatory amino acids; GABA, γ-aminobutyric acid; 
GABA t.o., GABA turnover; Tryp, tryptophan; 5-HT, serotonin; NMDA Ca2+; L-type Ca2+; G, G protein; cAMP , cyclic adenosine 
monophosphate; IPtase, inositol phosphatase; AP-1, activator protein 1; Sub P , substance P; SRIF, somatostatin. Arrows indicate  
increases or decesases in substance/activity.
6.2.4 lithium and related mood stabilizers

SECTION 6  treatment methods in psychiatry 1204
Side effects
Lithium
Since lithium has been in use for much of the latter half of the 
twentieth century, its side-effects proﬁ  le has been well described. 
Tremor and gastrointestinal distress, particularly diarrhoea, are generally dose-related, but some patients can have idiosyncratic sensitivity to these side effects, even at relatively low doses. Lithium-induced tremor can be countered with the beta-blocker propranolol in doses of 10 mg four times/day.
Side effects most likely to be associated with non-compliance 
or discontinuation of the drug include a sense of psychomotor slowing, cognitive dulling, acne or psoriasis, and weight gain. There is preliminary evidence that the anticonvulsants topiramate or zonisamide may help to reverse or stabilize lithium-related weight gain. Cognitive dulling could be treated with dose lowering, 
assessment of thyroid function, and T
3 (25–50 μg) augmentation

3 (25–50 μg) augmentation 
even with normal thyroid indices, folate augmentation, and, potentially, an acetylcholinesterase inhibitor such as donepezil (Aricept®).
Lithium interferes with the actions of ADH (i.e. vasopressin) 
because of its ability to block vasopressin-induced adenylate cycla-se. A syndrome of reversible diabetes insipidus  is thus induced 
which, in most patients, is not problematic, although in a small percentage of patients, excretion of large volumes of urine can be extreme, inconvenient, and disruptive of normal social routines and sleep. This can be countered with amiloride or the thiazide diuretics (however, the latter also increase lithium levels).
Lithium is clearly able to induce thyroid dysfunction with increases 
in thyroid-stimulating hormone, sometimes proceeding to more 
full-blown evidence of chemical hypothyroidism. The threshold for

full-blown evidence of chemical hypothyroidism. The threshold for 
treating lithium-related increases in thyroid-stimulating hormone has not been deﬁ  nitively identiﬁ  ed, but with some evidence of lower 
levels of free thyroxine being associated with increased levels of depression and other low thyroid indices being associated with increased cognitive dysfunction, replacement of thyroid hormones 
would appear indicated as thyroid-stimulating hormone begins to exceed normal levels . Whether thyroid supplementation can 
reverse or prevent these lithium-related abnormalities remains to be directly assessed in prospective studies.
Some investigators suggest that long-term lithium may be 
associated with slowly increasing creatinine levels  and a decrease 
in creatinine clearance.
(40) The incidence of these glomerular

(40) The incidence of these glomerular 
ﬁ ltration abnormalities in lithium-treated patients compared with 
age- and gender-matched controls remains controversial, as does the mode of treatment in the face of progressive changes in these indices. Given the availability of other potential mood-stabilizing agents, a reduction in lithium levels and supplementation or switch-ing to other agents would be a conservative measure, if tolerated. However, others recommend careful monitoring of continued lithium therapy because the effects of lithium discontinuation on creatinine levels are highly inconsistent.
Severe episodes of lithium intoxication are to be avoided since 
they can be associated with a syndrome of irreversible cerebellar dysfunction.
(42)The use of lithium with very high dose neuroleptic

(42)The use of lithium with very high dose neuroleptic 
treatment is also to be avoided since occasional idiosyncratic and irreversible organic brain syndromes have resulted on rare occasions. Marked EEG changes and tonic-clonic seizures were also observed with the combination of lithium and clozapine. Lithium can be associated with alterations in calcium homeostasis and frant 
hyperparathyroidism. As mentioned above, lithium can increase white cells and platelets via its action on granulocyte-macrophage colony stimulating factor.
Valproate has many lithium-like side effects which may also be 
additive in combination treatment. V alproate has a black box 
warning for rare hepatitis/pancreatitis and should not be given to children below two years of age . It can also cause low platelets,

warning for rare hepatitis/pancreatitis and should not be given to children below two years of age . It can also cause low platelets, 
and signs of bleeding tendency should be attended to. Because valproate increases homocysteine, routine supplementation with folate (and possibly also B6 and B12 in women of child bearing age) would appear prudent . Valproate can cause asymptomatic to 
symptomatic hyperammoniumemis; treatment with l-carnitine may be helpful. Zinc and selenium are anecdotally touted as pre-venting alopecia, but systematic evidence is lacking. Data are mixed as to whether valproate increases testosterone and causes the polycystic ovary syndrome (PCOS). Hirsutism is rarely seen in affectively ill patients and birth control pills will prevent PCOS. Valproate does increase the already high rates of menstrual irregu-
larities seen in women with bipolar disorder.

Carbamazepine has less weight-gain liability than lithium or 
valproate, but has greater potential for rash and rare but serious hematological problems. Carbamazepine  routinely causes a benign 
drop in white blood cells via its effects on colony stimulating factor; this can be countered by lithium . More problematic are 
agranulocytosis and aplastic anemia, estimated to occur in 1 in 20 000 to 50 000 patients. Patients should be warned to consult 
their physician  if they develop a fever, sore throat, or other infec-
tion that could emanate from a low white blood count, or bleeding gums or petechiae that could reﬂ  ect low platelets. Hyponatremia is 
more common with oxcarbazepine  than carbamazepine, but the 
hyponatremia of carbamazepine can be treated or prevented with lithium or demeclocycline. Low T
4 on carbamazepine is usually not 
reﬂ ective of hypothyroidism because TSH is not increased, BMR is

reﬂ ective of hypothyroidism because TSH is not increased, BMR is 
not decreased, and the degree of drop in T4 and free T4 may even be 
correlated with degree of antidepressive effect.
The major side-effects concern of lamotrigine is that of a severe 
rash , estimated to occur in 1 of 5 000 adults and 1 of 2 500 children. 
Even a benign rash should lead to drug discontinuation because there is no way to predict when a rash may progress to a Stevens-Johnson syndrome or T oxic Epidermal Necrolysis. Otherwise, the side-effects proﬁ  le of lamotrigine ﬁ  ts well with bipolar depres-
sion treatment because the drug is weight-neutral, non-sedating, and without sexual dysfunction or endocrine dysregulation.
The side-effects proﬁ  le of nimodipine and related dihydropyridine

The side-effects proﬁ  le of nimodipine and related dihydropyridine 
L-type calcium channel blockers differs considerably from that of lithium. These drugs are primarily used in cardiology for their anti-hypertensive and anti-arrhythmogenic effects. As such, they may cause side effects related to hypotension including dizziness 
and tightness in the chest . Unlike lithium, they are not typically 
associated with gastrointestinal distress and tend to be slightly constipating rather than associated with diarrhea. Therefore, they might be able to replace some component of lithium’s therapeutic action, as noted below, potentially without exacerbating some of lithium’s related side effects. Although these agents are often used in migraine prophylaxis, they can also be associated with headache on rare occasions. Redness and erythema with excessive warmth in

1205
the pretibial areas is also an occasional side effect of these agents, as 
is, more rarely, edema itself.
Nimodipine and related dihydropyridine L-type calcium chan-
nel blockers do not appear to share lithium’s ability to induce cog-nitive slowing and, in fact, these agents have been reported to improve performance in some preclinical models of learning and memory deﬁ  cits as well as in some clinical studies of patients with 
Alzheimer’s disease. This might be related to nimodipine’s ability to increase somatostatin upon chronic administration,
(43) although 
other mechanisms remain to be explored.
Also, in contrast to lithium, which is associated with a small inci-
dence of Epstein’s anomaly, verapamil is not teratogenic. While sys-tematic data are not available for the other dihydropyridine L-type calcium channel blockers, it is hoped that they will prove to be as safe as verapamil appears to be.
Indications and contraindications
Lithium

Lithium
The double-blind controlled studies of lithium in acute mania were positive several decades ago, and in the largest randomized study comparing lithium with placebo in a study primarily designed to evaluate the acute antimanic efﬁ  cacy of valproate, lithium and val-
proate appeared to show approximately equal efﬁ  cacy and both 
were superior to placebo.
(44) However, there appear to be a number 
of subtypes of illness with consistently higher or lower rates of 
response. As summarized in Table 6.2.4.1, a useful rule of thumb is 
that lithium is relatively less effective, with a low effectiveness rate 
of around 30 per cent in acute manic syndrome characterized by 
anxiety and dysphoria, comorbid substance abuse, comorbid med ical 
conditions, the pattern of illness of depression-mania-well inter-vals as opposed to mania-depression-well intervals, in those with a negative family history of bipolar illness in ﬁ  rst-degree relatives, in

those with evidence of EEG and neurological dysfunction, 
and in those with a pattern of rapid cycling or multiple prior episodes.
(2)
Lithium used to be considered contraindicated in pregnancy, 
but with the recognition that major cardiac malformations such as Epstein’s anomaly are rare (1 in 1 200 births), many clinicians and patients are deciding to continue lithium when it appears important to continued mood stability.
As discussed earlier, the evidence of verapamil’s acute antimanic efﬁ cacy is derived from a considerable series of small double-
blind studies. While the initial studies were unequivocally posi-tive, more recent studies have not been as positive comparing either verapamil with placebo or verapamil with lithium. Only very preliminary evidence is available for the acute antimanic efﬁ  -
cacy of nimodipine, with the open study of Brunet et al.
(45) being 
positive in six of six individuals.(18, 63) In placebo-controlled stud-

(45) being 
ies using an off-on-off-on design, 10 of 30 patients with refractory recurrent affective disorder responded and, in may instances, the antimanic efﬁ  cacy was demonstrated both in the on-phase and 
with symptom exacerbation in the off-phase.
(46) However, many of 
these individu als had ultra-rapid or ultra-ultra-rapid (ultradian) 
cycling patterns and most of the efﬁ  cacy data reﬂ  ected effective 
pharmacoprophylaxis of mania rather than acute antimanic efﬁ cacy per se .Dubovsky
(47) observed that a prior history of lithium response 
appears to be associated with a good response to verapamil. However, with the dihydropyridines we have observed some instances of response in those who were previously non-responders to lithi-um.
(46)Among those responsive to the drug were patients with

(46)Among those responsive to the drug were patients with 
ultra-rapid and ultradian cycling and those with a pattern of recur-rent brief depression. As indicated above, a number of these indi-viduals were rechallenged and responsiveness was conﬁ  rmed in 
an off-on-off-on design . Whether those bipolar patients with 
increased intracellular calcium would be among those responsive to the L-type calcium channel blockers also awaits completion of such a study, which is now under way.
A promising area of investigation is work using brain imaging, 
which has found that depressed patients with the classical pattern of relative frontal hypometabolism, and especially in the left insula, were among those who responded best to nimodipine, while equal-ly depressed patients with left insula hypermetabolism responded to carbamazepine.
(48)These data raise the possibility that regional 
topographies of blood ﬂ  ow or metabolism might ultimately help

topographies of blood ﬂ  ow or metabolism might ultimately help 
identify a subgroup of patients more responsive to the calcium-channel blocking agents. Also potentially helpful are data showing that nimodipine increases somatostatin in the CSF, and in one small study, that those with lower baseline CSF somatostatin were better responders to the drug.
(49)
Interactions
Lithium
Owing to its renal excretion, lithium has renally-mediated rather 
than hepatically-mediated drug-drug interactions. Lithium excre-
tion is decreased by medications such as thiazides, non-steroidal anti-inﬂ  ammatory drugs, angiotensin-converting enzyme inhibi-
tors, and, to a lesser extent, furosemide, and by physiological states such as dehydration, advanced age, and renal disease.
(50) Owing

(50) Owing 
to lithium’s poor therapeutic index, these interactions can result in clinical lithium toxicity unless appropriate dosage adjustment is made. In contrast, lithium clearance is less consistently affected by amiloride, aspirin, and sulindac, and increased with other medications with diuretic effects such as acetazolamide, manni-tol, aminophylline, caffeine, and theophylline, as well as during pregnancy.
Valproate, carbamazepine, lamotrigine
Valproate is FDA-approved for migraine prevention and treatment of acute mania. However, it is widely considered a mood 
stabilizer and used in long-term prophylaxis of both mood phas-es. A modicum of data support acute and prophylactic efﬁ  cacy in 
depression. V alproate decreases alcohol intake  in bipolar 
patients
(51) with this comorbidity and is useful in a wide range of 
anxiety syndromes.

patients
V alproate is contraindicated in pregnancy  because of a several 
percentage risk of neural tube defects (spina biﬁ  da) and, more 
recently noted, a substantial (20 per cent) incidence of other adverse events,
(52) as well as moderate to severe developmental delay in 
a sizeable number of children.
Carbamazepine  is approved for trigeminal neuralgia and the 
long-acting preparation of carbamazepine (Equetro®/T egretol Retard®) is approved only in acute mania, but can be considered in long-term prophylaxis for those not responsive to lithium or valproate. 6.2.4 lithium and related mood stabilizers

SECTION 6  treatment methods in psychiatry 1206
Its proﬁ  le of effectiveness is almost the converse of that of lithi-
um, with better effects in those with bipolar II illness, anxiety, 
and substance abuse comorbidity, mood incongruent delusions,
(53) and a negative family history of bipolar disorder in 
ﬁ rst-degree relatives. Carbamazepine should not be used in preg-
nancy because it carries about a 0.5 per cent risk of neural tube defects.
Lamotrigine is unique because it is approved for only preven-
tion of depressed episodes  and to a lesser extent, manic and mixed 
episodes. Robust efﬁ  cacy in acute depression has been seen in three 
studies, but not in four others, although the meta analysis remains signiﬁ  cantly positive. A small series of patients studied in Canada 
identiﬁ  ed correlates of positive response, including continuous 
cycling pattern and a personal and positive family history of 
anxiety disorders .
(54, 55) Only one of ﬁ  ve pregnancy case registries

(54, 55) Only one of ﬁ  ve pregnancy case registries 
showed a signiﬁ  cance for the increased occurrence of cleft lip and 
palate, and this agent clearly appears safer than valproate or carbamazepine. Its overall serious adverse event percentage of 1 per cent does not appear to be different from that of the general population.

Different calcium-channel blockers differentially affect carbamazepine levels. While verapamil and diltiazem increase carbamazepine levels substantially, potentially causing toxicity, this is not the case with nimodipine, isradipine, or amlodipine. Preliminary data from our group and others suggest that car-bamazepine decreases nimodipine levels after a 60 mg challenge dose. In our study, group mean peak nimodipine levels during treatment with carbamazepine were about one-half those observed during treatment with nimodipine alone, although this ﬁ  nding 
showed only a trend level of signiﬁ  cance, probably due to small 
sample size.
When calcium channel blockers are added to ß-adrenergic 
blocking agents, depression of ventricular function, cardiac slowing, and atrioventricular block can result. Combining calcium channel blockers with ß-adrenergic blocking agents may produce 
hypotension. Verapamil and nitrendipine increase plasma concen-

trations of digoxin and produce bradycardia, hypotension, or atrioventricular block.
Effects of withdrawal
Lithium
In addition to the variety of predictors of relative lithium nonresponsiveness from the outset, two relatively new and differ-
ent mechanisms for the development of treatment resistance or 
loss of efﬁ  cacy have been uncovered during long-term follow up 
in patients who are initially responsive. The ﬁ  rst of these is the 
apparent development of tolerance characterized by an increasing frequency and/or severity of breakthrough episodes despite good compliance and consistent maintenance of lithium blood levels. In a group of 66 patients referred to the NIMH because of lithium nonresponsiveness, 23 patients (34.8 per cent) displayed this 
apparent tolerance pattern .
(55)Although it has not been system-

atically studied, the initial therapeutic manoeuvres in the face of such loss of efﬁ  cacy at maximum tolerated doses would appear to 
be augmenting lithium’s effects with other putative mood-stabilizing
agents with different mechanisms of action, and if lithium should be discontinued, a consideration of its reinstitution with a hope 
for renewal of responsivity.
In contrast with this tolerance pattern in which patients suffer 
breakthrough episodes despite remaining under treatment, the phenomenon of lithium-discontinuation-related refractoriness refers to a small group of patients who have done extremely well on their long-term lithium, discontinue the drug, suffer additional relapses, and then fail to re-respond once lithium is reinstituted. This phenomenon accounted for nine of the 66 patients (13.6 per cent) who presented to us as lithium-refractory.
(56)The average

(56)The average 
time well on lithium was 6.6 years, substantially greater than the average well interval of 1.5 years prior to instituting lithium therapy, strongly suggesting that lithium had been effective in these individuals, and if they had remained on the drug, they might have remained well. Sadly, for each of these individuals, this did not prove to be the case.
One patient had been well on lithium for more than 16 years 
and tapered lithium slowly, suggesting that neither the duration of time well nor the use of a slow taper would necessarily prevent the development of discontinuation-induced refractoriness. A number of other investigative groups have observed such a phenomenon.
(57)

(57)
In these studies, discontinuation-induced refractoriness occurred in anywhere from 3.6 per cent to 18.6 per cent of patients, with a total of 39 of 321 (12.1 per cent), and 12 of 92 (13 per cent) in studies that tracked responders only. Even if it only occurs in about 10 per cent of patients who discontinue their lithium, it would nev-ertheless appear to be of considerable clinical import and should be included in the informed consent process so that the patient has all of the available data when making decisions of whether or not to continue treatment. That is, in considering the risk-beneﬁ  t of 
stopping lithium, a patient should not only know the very high 
risk of relapse  (50 per cent in the ﬁ  rst ﬁ  ve months after discontin-
uing lithium, 80–90 per cent after 1.5 years,
(58) but also that there 
isno guarantee that responsivity would be as rapid, robust, or 
complete  as previously experienced, and that a small subgroup of

complete  as previously experienced, and that a small subgroup of 
individuals, perhaps as many as 10 per cent, will not achieve the same good response that they had previously.
Valproate will displace carbamazepine from its protein binding and inhibit the epoxide hydrolase from converting the active epoxide to the inactive diole. Thus, carbamazepine dose will need to be 
decreased when used in combination with valproate .V alproate 
will double lamotrigine levels  such that dosing should be one-half 
that of normal.
Carbamazepine as a potent 3A4 inducer has many drug-drug 
interactions . It will decrease levels of oestrogen such that high 
dosage forms need to be used with birth control pills . It will lower 
levels of lamotrigine, haloperidol, aripiprazole, and many other compounds.
Inhibition of 3A4 will notably increase carbamazepine

Inhibition of 3A4 will notably increase carbamazepine 
levels  and potentially cause toxicity if a patient is at or near their 
side-effects threshold. Erythromycin  and its analogues, verapamil, 
and diltiazem  are such examples, and patients should be warned to 
check with their pharmacists about its many other interactions. Side effects can be avoided with lower carbamazepine doses in advance of such drugs being administered.
Each of these drugs can be discontinued rapidly without a major 
withdrawal syndrome. T olerance to the efﬁ  cacy of each of these

1207
agents has been observed in isolated cases or small series. Increasing 
doses and/or switching to or adding other agents without cross-tolerance (mechanistically different) are typically used clinically 
(8)
In instances of tolerance development a period of time off the new ineffective drug may be associated with transient renewal of efﬁ  cacy. 
Theoretical, but unproven ways of slowing or minimizing toler-ance development include: using more maximally tolerated doses, rather than minimally effective ones; holding doses stable and not decreasing them unnecessarily; using combination of drugs; and treating earlier as opposed to later in the course of illness.

Because so few patients have been studied with the L-type calcium channel blockers in long-term prophylaxis, it is uncertain to what extent patients may become tolerant to these agents. However, since tolerance has been observed to virtually every other putative mood-stabilizing agent, it is likely that this will also occur with nimodipine and related agents. Similarly, it is uncertain whether the phenomenon of discontinuation-related refractoriness observed with lithium would extend to the class of L-type calcium channel blockers; while we have not observed this phenomenon in our cohort of nimodipine responders (63), only a small group of patients has been studied to date.
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6.2.5 Antipsychotic and 
anticholinergic drugs
Herbert Y. Meltzer and  William V. Bobo
The discovery by Delay and Denicker in 1953 that chlorpromazine

The discovery by Delay and Denicker in 1953 that chlorpromazine 
was highly effective in alleviating delusions, hallucinations, and disorganized thinking, was the seminal breakthrough in the treat-ment of schizophrenia, the ﬁ  rst agent to produce sufﬁ  cient relief of 
core psychotic symptoms to permit life outside of institutions for many patients with schizophrenia, and even a return to a sem-blance of function within normal limits. Chlorpromazine and the other related typical antipsychotic drugs which were introduced over the next 30 years have proven to be of immense beneﬁ  t to 
vast numbers of people who experience psychotic symptoms as a

1209
component of a diverse group of neuropsychiatric and medical dis-
orders, as well as drug-induced psychoses. These drugs have been invaluable in providing clues to the aetiology of schizophrenia and other forms of mental illness with psychotic features and as tools in understanding fundamental neural processes, especially those involving dopamine, a key neurotransmitter involved in psychosis. This class of drugs has now been supplanted by the so-called atypical antipsychotic drugs, of which clozapine is the prototype. This chapter will describe the various classes of antipsychotic agents, with emphasis on the atypical antipsychotic drugs, their beneﬁ  ts 
and adverse effects, recommendations for use in clinical practice, and mechanism of action. The drugs used to treat the extrapyrami-dal side-effects (EPS) produced mainly by the typical antipsychotic drugs are also considered.
The classes of antipsychotic drugs
Antipsychotic drugs have been classiﬁ  ed into two broad categories:

Antipsychotic drugs have been classiﬁ  ed into two broad categories: 
typical and atypical.(1) Typical antipsychotic drugs are those which 
(typically) produce EPS at clinically effective doses, including par-kinsonism (muscle rigidity, tremor, bradykinesia), acute dystonic reactions, dyskinesias, akathisia (restlessness), and tardive dyskine-sia. They are also called neuroleptics because of their inhibitory effect upon locomotion activity. They are sometimes referred to as ﬁ rst generation antipsychotic drugs, but this has multiple problems 
as a class designation. The prototype of the atyipcal class of agents is clozapine which was ﬁ  rst discovered during the early stages of 
the development of the drugs called ﬁ  rst generation agents. The 
major mode of action of typical neuroleptics is to block dopamine D
2 receptors in the limbic system, which includes the nucleus 
accumbens, stria terminalis, and amygdala.

The typical antipsychotic drugs are members of a variety of 
chemical families (Table 6.2.5.1). They vary in afﬁ  nity for the D2
receptor, with low afﬁ  nity drugs such as chlorpromazine, which 
require high doses for clinical efﬁ  cacy, to high afﬁ  nity drugs such as 
haloperidol, which are effective at lower doses (Table 6.2.5.1). Kapur and Seeman
(3) have proposed that the rate of dissociation of 
all antipsychotic drugs from the D2 receptor provides the basis for

all antipsychotic drugs from the D2 receptor provides the basis for 
the distinction between typical and atypical antipsychotic drugs, with atypical antipsychotic drugs dissociating more rapidly. While this is true for clozapine and quetiapine, the atypical drugs risperi-done, sertindole, olanzapine and asenapine dissociate no more rapidly or even slower than haloperidol. As such, ‘fast dissociation’ cannot provide the pharmacological basis for atypicality for most of the drugs that are considered atypical.
Low-potency typical neuroleptic agents are those in which the 
usual dose range in schizophrenia is equal to or greater than 200 mg/day, while mid- to high-potency agents are those in which the dose range is between 2 and 175 mg/day. In general, the low-potency drugs are more sedative and more hypotensive than the high-potency agents but also have less of a tendency to produce

extrapyramidal side-effects. The typical antipsychotic drugs differ 
from one another with regard to potential for other side-effects, e.g. weight gain and hypotension, but have comparable efﬁ  cacy as 
antipsychotic agents.
(4)
Atypical antipsychotic drugs are those antipsychotic agents with 
a signiﬁ  cantly lower propensity to produce EPS at clinically effec-
tive doses.(1) They are also characterized by a more diverse and complex pattern of pharmacological activity, including serotonin 
(5-hydroxytryptamine)2A and dopamine D2 antagonism as well as 
a variety of activities at other receptors whose contribution to their mode of action is still being elucidated.
(2) Substituted benzamides, 
e.g. amisulpride, also have low EPS at clinically effective doses and 
may constitute another class of atypical agents. New classes of atypical antipsychotic drugs are emerging from research with con-siderable frequency at the current time.

The prototypical atypical antipsychotic drug is clozapine, a 
dibenzodiazepine (Table 6.2.5.1).
(5) Others include aripiprazole,(6)
olanzapine, quetiapine, paliperidone, risperidone, sertindole, zipra-sidone and zotepine, while iloperidone,
(7) asenapine,(8) and laur-
asidone(9) are in development and have a similar pharmacology to 
that of risperidone. These drugs are all more potent 5-HT2A than 
D2 receptor antagonists as well as multireceptor antagonists(9, 10)
except for aripiprazole, which is a dopamine D2 receptor partial 
agonist. Bifeprunox is also a partial D2 agonist. It lacks 5-HT2A
receptor blocking properties, relying instead on 5-HT1A partial 
agonism to reduce serotonergic tone. Amisulpride and remoxipride are substituted benzamides. Both are selective D
2/D3 antagonists.(2)

Table 6.2.5.1  Selected antipsychotic drugs and classiﬁ  cation 
schemes
Drug name Trade 
nameChemical class General 
classD2 
potency*
Aripiprazole Abilify Dihydrocarbostyril Atypical
Chlorpromazine Thorazine Phenothiazine Typical LowClozapine Clozaril Dibenzazepine AtypicalDroperidol Inapsine Butyrophenone Typical MidFluphenazine Prolixin Phenothiazine Typical HighHaloperidol Haldol Butyrophenone Typical HighLoxapine Loxitane Dibenzazepine Typical Mid
Mesoridazine Serentil Phenothiazine Typical Low
Molindone Moban Dihydroindolone Typical MidOlanzapine Zyprexa Thiobenzodiazepine AtypicalPaliperidone Invega 9-hydroxy 
metabolite of 
risperidoneAtypical
Perphenazine Trilafon Phenothiazine Typical Mid

Pimozide Orap Butyrophenone Typical MidPromazine Phenothiazine Typical MidQuetiapine Seroquel Dibenzothiazepine AtypicalRisperidone Risperdal, 
Risperdal 
CONSTABenzisoxazole Atypical
Thioridazine Mellaril Phenothiazine Typical Low
Tiotixene Navane Thioxanthene Typical HighTriﬂ  uoperazine Stelazine Phenothiazine Typical MidZiprasidone Geodon Benzisothiazole Atypical
* Classiﬁ  cation on the basis of potency of D2 receptor binding for typical antipsychotic 
drugs only6.2.5 antipsychotic and anticholinergic drugs

SECTION 6  treatment methods in psychiatry 1210
Remoxipride was withdrawn shortly after its introduction because 
of a high rate of aplastic anaemia.
As will be discussed, the atypical antipsychotic drugs differ not 
only with regard to side-effects but also with regard to efﬁ  cacy.(11,12)
Atypical antipsychotic agents have been shown to have advantages, 
albeit modest, in treating negative mood symptoms(13–15) and to 
improve cognitive dysfunction in schizophrenia and perhaps other psychiatric disorders.
(16–18)
There is abundant evidence that dopamine plays a key role in the aetiology of psychosis and the action of antipsychotic drugs.
(19)
The antipsychotic action of the typical antipsychotic drugs is highly correlated with their afﬁ  nities for D
2 receptors. Amphetamine

(19)
2 receptors. Amphetamine 
and methamphetamine, which increase synaptic concentrations of dopamine, have been found to exacerbate delusions and hallucinations in some patients with schizophrenia This effect is believed to be due to stimulation of a subgroup of D
2 receptors 
in mesolimbic nuclei.(19, 20) The cell bodies of mesolimbic 
dopamine neurones reside in the ventral tegmentum, the so-called A10 area, and have terminals in the nucleus accumbens, stria terminalis, and olfactory tubercle. The outﬂ  ow of these regions 
to the thalamus and the cortex is believed to mediate psychotic symptoms. The firing rate of the mesolimbic dopaminergic neurones is subject to multiple inﬂ  uences, including stimulatory 
serotonergic input from the median raphe.
(21) The origin of the

(21) The origin of the 
dopamine neurones that terminate on cholinergic neurones in the basal ganglia is the substantia nigra, the so-called A9 region.
(20)
Blockade of striatal D2 receptors in this pathway leads to the extra-
pyramidal side-effects produced by antipsychotic agents. A group of ventral tegmental dopamine neurones project to vari-ous regions of the cortex and comprise the mesocortical dopamine system. There is extensive evidence that these neurones are impor-tant for cognition, especially working memory,
(22) as well as nega-
tive symptoms.(23) Neuroleptic drugs occupy 80 to 95 per cent of 
striatal D2 receptors in patients with schizophrenia at clinically 
effective doses, though a lower blockade threshold of 60 per cent for improving positive symptoms has been identified.
(24) 
Extrapyramidal side-effects occur above 80 per cent occupancy of these receptors. Blockade of D
2 receptors in the anterior pitu-

(24) 
itary gland is the basis for their ability to stimulate prolactin secretion.
(25)
The prefrontal cortex has relatively low concentrations of D2
receptors and has a higher density of D1, D3 and D4 dopamine 
receptors.(20) The activation of D1 receptors in prefrontal cortex 
may be especially critical for normal working memory and other executive type functions subserved by this brain region. However, no D1 agonists are available for treatment at the current time, although several are in development. Drugs which selectively block D
4 receptors have not been found to have an antipsychotic effect.(26)
There are only limited data regarding the aetiologic or pharmaco-logical signiﬁ  cance of D
3 receptors in schizophrenia.
The typical antipsychotic drugs vary in their in vitro  and in vivo
afﬁ nities for receptors such as the dopamine D1, histamine H1,

muscarinic, α-1 and α-2 adrenergic, and serotonergic receptors 
(Table 6.2.5.2), which mediate effects on arousal, extrapyramidal, cognitive, cardiovascular, gastrointestinal, and genitourinary func-
tion (Table 6.2.5.3).
(27)Thioridazine is a relatively potent antimuscarinic agent. Most of 
the low-potency antipsychotic agents are potent α1 and H1 antago-
nists. These afﬁ  nities contribute to hypotension and weight gain, 
respectively. While some typical antipsychotic drugs have a high afﬁ nity for 5-HT
2A receptors, their afﬁ  nities for D2 receptors are 
even higher, which diminishes the beneﬁ  cial effects of the 5-HT2A
receptor blockade. The speciﬁ  c receptor proﬁ  le of each atypical

receptor blockade. The speciﬁ  c receptor proﬁ  le of each atypical 
antipsychotic is of special interest because it may account for criti-cal differences among these compounds, especially in terms of side effect burden (Table 6.2.5.4).
The afﬁ  nities of the atypical antipsychotic drug have been related 
to their efﬁ  cacy and side effect proﬁ  les. As noted above, the most 
important determinant of atypicality for most of the currently available agents of this type is that they are more potent 5-HT
2A
than D2 receptor antagonists. An exception is aripiprazole, which 
combines potent 5-HT2A antagonism and 5-HT1A agonism, with 
partial D2 receptor agonism. Another exception is amisulpiride, 
which is a selective D2/3 antagonist with little pharmacological 
activity at 5-HT2A receptors. Combined 5-HT2A with less potent

activity at 5-HT2A receptors. Combined 5-HT2A with less potent 
D2 antagnoism is the most consistent principle yet discovered to produce a separation between antipsychotic action and interfer-ence with motor function. This hypothesis arose from showing that it could distinguish clozapine, the prototypical atypical antipsy-chotic drug, and a series of other atypical antipsychotic compounds from those which have typical properties.
(28) These studies 
suggested that the low potential for extrapyramidal side-effects of clozapine, and subsequently, olanzapine, quetiapine, risperidone, iloperidone, ziprasidone, paliperidone and asenapine are due, in part, to their relatively stronger 5-HT
2 antagonist and weak D2

antagonist properties. The serotonin-dopamine interaction in the nigrostriatal and mesolimbico-cortical pathways appears to be mediated by stimulation of 5-HT
2A receptors, which are located on 
dopaminergic cell bodies, whereas antagonism of these receptors may release these neurones from tonic inhibition.
The atypical antipsychotic agents have the ability to increase pre-
frontal cortical dopaminergic activity compared with subcortical dopaminergic activity.
(29) The ability to increase the release of 
dopamine in the prefrontal cortex may be important for atypical antipsychotic agents to improve cognition and negative symptoms. It may also contribute to decreasing the release of dopamine in the mesolimbic region, because prefrontal dopamine neurones modu-late the activity of corticolimbic glutamatergic neurones that inﬂ  u-
ence the release of dopamine from nerve terminals in the limbic region.
(22) Typical neuroleptic drugs do not share this ability to

(22) Typical neuroleptic drugs do not share this ability to 
increase dopamine efﬂ  ux in prefrontal cortex. Clozapine and some 
of the other atypical antipsychotic drugs that are also potent 5-HT
2A antagonists, but not typical neuroleptics, also produce 
marked increases in prefrontal cortical and hippocampal acetyl-choline efﬂ  ux.
(30) These atypical agents also produce marked 
increases in noradrenaline efﬂ  ux in the prefrontal cortex which is 
correlated in time and magnitude with the increase in extracellular dopamine.
(31) It is of interest that in rodents, combining ritanserin 
(a mixed 5-HT2a/2B/2C antagonist) or M-100907 (a selective 5-HT
2A antagonist) with a selective D2/3 antagonist resulted in 
increased prefrontal dopamine release.(32, 33) The combination of

increased prefrontal dopamine release.(32, 33) The combination of 
haloperidol and M-100907 also increased prefrontal dopamine release, with the greatest effects observed when lower doses of halo-peridol were used.
(34) Because reduced noradrenergic and dopami-
nergic function in prefrontal cortex and hippocampus has been

1211
Table 6.2.5.2  Afﬁ  nities of selected antipsychotic drugs at various neuroreceptors
Drug name D2 5-HT1A5-HT2A5-HT2C α-1 α-2 H-1 M-1
Aripiprazole 0.95 5.6 4.6 181.0 25.0 74.0 29.0 >6K
Chlorpromazine 2.0 >3K 3.2 26.0 0.28 184.0 0.18 47.0
Clozapine 431.0 105.0 13.0 29.0 l.6 142.0 2.0 14.0
Droperidol 0.25 (173)NA NA NA NA NA NA NA
Fluphenazine 0.54 145.0 7.4 418.0 6.4 314.0 7.3 >1K
Haloperidol 2.0 >1K 73.0 >10K 12.0 >1K >3K >10K
Loxapine 10.0 >2K 3.9 21.0 31.0 151.0 2.8 175.0
Molindone 63.0(43)>3K(43) 320.0(43)>10K(43) >2K(43) >1K(43) >2K(43) NA
Olanzapine 72.0 >2K 3.0 24.0 109.0 314.0 4.9 24.0
9-OH risperidone* 9.4 637.8 1.9 100.3 2.5 4.7 5.6 >10K
Perphenazine 1.4(43)421.0(43)5.6(43)132.0(43)10.0(43)810.5(43)8.0(43)NA
Pimozide 0.65(43)650.0(43)19.0(43)>3K(43) 197.7(43)>1K(43) 692.0(43)800.0(174)
Quetiapine 567.0 431.0 366.0 >1K 22.0 >3K 7.5 858.0
Risperidone 4.9 427.0 0.19 94.9 5.0 151.0 5.2 >10K

Thioridazine 10.0 108.0 11.0 69.0 1.3 134.0 14.0 33.0Tiotixene 1.4 410.0 111.0 >1K 12.0 80.0 12.0 >10K
Triﬂ  uoperazine 1.3
(43)950.0(43)13.0(43)378.0(43)24.0(43)653.7(43)63.0(43)NA
Ziprasidone 4.0 76.0 2.8 68.0 18.0 160.0 130.0 >10K
All receptor binding afﬁ  nities are reported as Ki (nM) using National Institutes of Mental Health (NIMH) Psychoactive Drug Screening Program (PDSP) certiﬁ  ed data, available on line at 
http://pdsp.cwru.edu/pdsp.php, unless otherwise speciﬁ  ed. In general, the lower the Ki (nM) value, the higher the binding afﬁ  nity for the drug at a given receptor site.
NA = human cloned receptor data not available
* 9-hydroxy (9-OH) risperidone is marketed as paliperidone
Table 6.2.5.3  Hypothesized therapeutic and adverse effects of receptor occupancy by antipsychotic drugs

Target receptor Pharmacological activity Therapeutic effect(s) Adverse effect(s)
Dopamine D2 Antagonism or partial agonist effects Reduction of positive symptoms Extrapyramidal effects (EPS)
Hyperprolactinemia
Serotonin (5-HT) 1AFull or partial agonist effects Cognitive enhancement
Reduction of mood and anxiety symptoms
5-HT 2A Antagonism Reduction of negative symptoms
Reduction of EPS
Increased deep sleep
5-HT 2CAntagonism Reduced anxiety symptoms Weight gain
Adrenergic α-1 Antagonism Orthostatic hypotension
Dizziness
Adrenergic α-2 Antagonism Reﬂ  ex tachycardia
Histamine H-1 Sedation Sedation
DrowsinessWeight gain
Muscarinic 
(cholinergic) M-1Antagonism Reduction of EPS Blurry vision
Exacerbation of acute angle closure glaucoma
Sinus tachycardiaConstipation
Urinary retention

Memory dysfunction
Adapted from Kelly, D.L. and Love, R.C. Ziprasidone and the QTC interval: pharmacokinetic and pharmacodynamic considerations, P sychopharmacology Bulletin, 35, 66–79, 
copyright 2001, MedWorks Media Global, LLC.6.2.5 antipsychotic and anticholinergic drugs

SECTION 6  treatment methods in psychiatry 1212
associated with negative symptoms and cognitive impairment in 
schizophrenia,(22, 35)  the cortical release of these two neurotransmit-
ters, and possibly also acetylcholine, may provide a pharmacological basis for the advantages of atypical antipsychotics over typical neu-roleptic drugs in the treatment of these critical symptom domains. In patients with schizophrenia who were stabilized on typical neu-roleptics, the addition of mianserin, a 5-HT
2A/C and adrenergic α-2
antagonist, was associated with improved neurocognitive perfor-mance,
(36)adding further support to a role of 5-HT2A receptors in 
the treatment of cognitive dysfunction in schizophrenia.
The importance of serotonin receptors other than 5-HT2A for 
the action of antipsychotic drugs has received considerable attention. Activation of 5-HT
1A receptors are believed to have a 
dopamine modulating effect similar to that of 5-HT2A antago-

nism.(37) Under experimental conditions, 5-HT1A agonists have 
been shown to stimulate cortical dopamine release(38, 39) and, in 
schizophrenic patients who were stabilized on haloperidol, the addition of tandospirone, a 5-HT
1A partial agonist, resulted in 
improved neurocognitive performance.(40) This effect has also been 
demonstrated more recently for buspirone, another 5-HT1A partial 
agonist.(41) Serotonin-1A receptors may be important for cognitive effects of at least some of the atypical antipsychotic drugs that are 
active at this receptor site. Activity at 5-HT1A receptors is not shared 
by all antipsychotic drugs (Table 6.2.5.2), however. Antagonism of 5-HT
2C receptors also appears to result in cortical dopamine and 
norepinephrine release, as well as in the nucleus accumbens.(42)

norepinephrine release, as well as in the nucleus accumbens.(42) 
The cognitive effects of selective 5-HT2C antagonists added to typi-
cal neuroleptic drugs in patients with schizophrenia have not been examined. As is the case with 5-HT
1A activity, not all atypical anti-
psychotic drugs are active at 5-HT2C receptors (Table 6.2.5.2). Like 
antagonism at histamine H1 receptors,(43) 5-HT2C antagonist activ-
ity may be related to antipsychotic induced weight gain.(44)
Atypical antipsychotics may display regional selectivity in terms 
of their dopaminergic activity, relative to typical neuroleptics. For instance, atypical antipsychotic drugs appear to preferentially block cortical D
2 receptors, relative to those located in the striatum.(45, 46) 
Haloperidol results in proportionally equivalent D2 blockade in

Haloperidol results in proportionally equivalent D2 blockade in 
both brain regions.(47)The atypical antipsychotics also increase the 
expression of the early intermediate gene c- fos, in the prefrontal 
cortex and the shell of the nucleus accumbens, while sparing the core of the latter region and the striatum. Typical neuroleptic drugs have the opposite effect on c- fos expression. Sparing the dorsal Table 6.2.5.4  Adverse effects of selected antipsychotic drugs
Typical antipsychotic drugs
EPS Tardive 
dyskinesiaProlactin elevation Sedation Weight gain Orthostasis Anti-cholinergic Diabetes 
exacerbation & 
dyslipidemia
ChlorpromazineFluphenazine
Haloperidol
LoxapineMesoridazine
Molindone
PerphenazineThioridazine
Tiotixene
Triﬂ  uoperazineSome (for low 
potency* drugs) 
- +++  (for high-
potency* drugs)++ - +++ ++  - +++  (risk 
higher for high-potency drugs)Some 
(for high 
potency 
drugs) - +++  
(for low-
potency

(for high 
potency 
(for low-
potency 
drugs); ? least for 
molindoneSome 
(for high 
potency 
(for low-
potency 
molindoneSome (for 
high potency 
(for low-potency 
drugs)Some (for high 
potency drugs) - +++  (for low-
potency drugs)+ - ++
* See Table 6.2.5.1 for list of low-, mid-, and high-potency (with respect to dopamine D2 receptor blockade) antipsychotic drug s
Adapted from the International Psychopharmacology Algorithm Project (IPAP) algorithm for the treatment of schizophrenia, availa ble at www.ipap.org, copyright 2008 International 
Psychopharmacology Algorithm Project (IPAP)
Atypical antipsychotic drugs
dyskinesiaProlactin elevation Sedation Weight gain Orthostasis Anti-cholinergic Glucose 
dysregulation & 
Amisulpride + Rare +++ + 0 - ++ 00

Aripiprazole 0 - + 0 - + 0 0 - + 0 - ++  - ++ 00
Clozapine 0 0 Transient +++ +++ +++ +++ +++
Olanzapine 0 - + (if < 10 mg/day) Rare + (if < 20 mg/day) ++ +++ + + +++
Quetiapine 0 Rare 0 ++ +  - ++ ++ 0 - ++ +
Risperidone + (less if < 4 mg/day) Rare +++ + +  - ++ ++ 0 +
Ziprasidone 0 - + Rare 0 - + 0 - ++ 0 + - ++ 00
Sufﬁ  cient data for paliperidone, iloperidone and asenapine are not yet available for inclusion in this table.

1213
striatum is believed to be related to the low potential for extrapyra-
midal side-effects of these agents.(2, 21)
Clozapine, olanzapine, risperidone, and quetiapine are able 
to block the interference in prepulse inhibition produced by 
d-amphetamine, apomorphine, or phencyclidine at doses that do not interfere with locomotor function. Clozapine and M100907 are able to block the effects of phencyclidine, an N-methyl-D-aspartate 
receptor antagonist, on locomotor activity in rodents. This suggests the ability of rat 5-HT
2A-receptor blockade to block some of 
the effects of phencyclidine which is one of the more important models for schizophrenia.
(2, 21) In a recent single photon emission 
tomography (SPECT) study, patients with schizophrenia who received treatment with clozapine evidenced reduced NMDA-active radiotracer binding compared with healthy controls, drug free patients with schizophrenia, and patients with schizophrenia who were treated with typical neuroleptics.

(48) The extent of 
involvement of other atypical antipsychotic drugs relative to typical antipsychotics at NMDA receptors and other glutamatergic targets is an area of active interest. Other receptor targets that are of special interest in terms of improving cognitive functioning and selected psychotic symptoms include M1 muscarinic, α-7 nicotinic, 
andα-1 and α-2 adrenergic receptors.
Administration, pharmacokinetics, 
and dosage
Administration
(a) Typical antipsychotic drugs
The major uses of the antipsychotic drugs are for the treatment 
of schizophrenia, mood disorders typically with psychotic features, and senile psychoses.
(4, 49) Other indications are discussed elsewhere 
in this book in the consideration of the management of speciﬁ  c

in this book in the consideration of the management of speciﬁ  c 
disorders, such as T ourette’s syndrome, and aggression. The major advantage of the typical neuroleptic drugs is their ability to improve positive symptoms, i.e. delusions and hallucinations. Administration of typical neuroleptic drugs leads to the complete or nearly complete elimination of positive symptoms and disorganization of thought and affect in about 60 to 70 per cent of patients with schizophrenia and an even higher proportion of those with psychotic mania and psychotic depression.
(49) The antipsychotic response in

(49) The antipsychotic response in 
schizophrenia and mania is sometimes apparent within a few days in many patients but usually takes up to several weeks or months. A reasonable duration for a therapeutic trial with one of these agents is 4 to 6 weeks. It is not appropriate to switch medications after 1 or 2 weeks, even if a response is not apparent, unless side-effects pose a serious problem. Positive symptoms (delusions and hallucinations) do not respond to typical neuroleptic drugs in about 10 per cent of schizophrenic patients even during the ﬁ  rst epi-
sode.
(50) Another 20 per cent of patients with schizophrenia develop 
resistance to these agents during the subsequent course of their illnesses.
(51) Development of resistance to typical neuroleptic 
drugs may occur at any time during the course of treatment, even after many years of control of positive symptoms. Such patients are more likely to respond to clozapine
(51) or one of the other atypical 
antipsychotics.(50, 51)

The average doses of the typical neuroleptic drugs are given in 
Table 6.2.5.5. The best results with these drugs in terms of efﬁ  cacy 
and side-effects may be expected with the lowest dose needed to produce control of positive symptoms with the fewest extrapyra-
midal side-effects.(4, 49)
There are some patients for whom higher doses are indicated, but 
most controlled studies have failed to ﬁ  nd beneﬁ  ts from high-dose 
strategies of combining two or more of these agents. Increasing the 
dose of these agents when patients fail to respond rapidly, for exam-ple within days, is not recommended. Augmentation with a benzo-diazepine may be useful to decrease anxiety until the lower doses of neuroleptic drugs produce adequate control of positive symp-toms.
(4, 49) Patients who may require higher doses of neuroleptic

(4, 49) Patients who may require higher doses of neuroleptic 
drugs to respond adequately are at greater risk of hyperprolactinae-mic effects, EPS, and tardive dyskinesia and are generally better treated with an atypical antipsychotic drug.
However, the improvement in positive symptoms which is often 
achievable with the typical antipsychotic drug is only one element in the treatment of schizophrenia and is not sufﬁ  cient grounds for 
judging response to be adequate. Additional efﬁ  cacy factors of 
major importance are summarized in Table 6.2.5.6.
T olerability and safety factors, such as compliance, tardive dyski-
nesia, weight gain, and medical morbidity are also major elements in outcome and are inﬂ  uenced by the choice of a typical or atypical 
antipsychotic drug. Typical neuroleptic drugs are not as effective for improving primary negative symptoms of schizophrenia in the majority of patients.
(52, 53) There is a consensus that typical neuro-

leptic drugs can improve negative symptoms that are secondary to positive symptoms and depression while at the same time possibly causing secondary negative symptoms due to their ability to pro-duce extrapyramidal side-effects.
(52) Abnormalities in speciﬁ  c 
domains of cognition (Table 6.2.5.6) are present in ﬁ  rst-episode 
schizophrenic patients at a moderate to severe level and show slight to moderate, rarely severe, deterioration during the course of ill-ness.
(54, 55)  Approximately 85 per cent of patients with schizophrenia 
are clinically impaired in one or more domains of cognition.(55, 56)
Cognition has been shown to be perhaps the most critical determi-nant of functional capacity among patients with schizophrenia, even more so than positive symptoms.
(57) Typical neuroleptic drugs 
usually do not improve cognitive function.(58) Those typical

usually do not improve cognitive function.(58) Those typical 
neuroleptic drugs such as thioridazine and mesoridazine, which have strong antimuscarinic properties, may produce further impairment in some memory functions.
(58)
All of the typical neuroleptic drugs are likely to be equally effective 
in treating either the initial presentat ion or recurrent psychosis due to 
breakthrough of symptoms, despite compliance, or because of having 
stopped medication(4, 49, 51)  First-episode patients with schizophrenia 
usually require much lower doses than patients with two or more episodes, suggesting some progression of the disease process or devel-opment of tolerance to the mechanism of action of these drugs.
(59)
Doses for more chronic patients should be in the range of 5 to 10 mg haloperidol equivalents per day (Table 6.2.5.5) for up to 4 to 6 weeks 
unless there is a major need for chemical means to prevent harm to

unless there is a major need for chemical means to prevent harm to 
self or others, to decrease excitement, or induce sleep.
(60) Auxiliary 
medications for anxiety and sleeplessness, for example benzodiaze-pines, may supplement these low doses of antipsychotics.
(61)
Parenteral injections of haloperidol, chlorpromazine, or other 
neuroleptics may be needed for patients who refuse oral medication or where very rapid onset of action is needed to control acutely dangerous behaviours if less restrictive means either fail or cannot be utilized safely. Commonly, haloperidol (2–10 mg) with or without lorazepam (2–4 mg) is delivered intramuscularly every 30 6.2.5 antipsychotic and anticholinergic drugs

SECTION 6  treatment methods in psychiatry 1214
to 60 minutes as required, up to three doses. Doses of haloperidol 
given intramuscularly in such situations generally should not exceed 18 mg per day. Oral medication should be substituted as soon as feasible. If positive symptoms fail to respond to a single 
trial of a typical neuroleptic drug at adequate doses in patients with 
schizophrenia, there is evidence that switching to another typical antipsychotic, even of a different chemical class, is unlikely to pro-
duce greater control.
(4, 49, 51) This is likely to be true for other indi-
cations for the use of antipsychotic agents as well.
In cases of repeated illness relapse due to poor compliance or 
when patients prefer it, the use of long acting (e.g. depot) injectable antipsychotic medications, typically administered once every

when patients prefer it, the use of long acting (e.g. depot) injectable antipsychotic medications, typically administered once every 
2–4 weeks, may be used. The use of injectable antipsychotic medication has been associated with lower rates of relapse and rehospitalization and greater global improvement compared with 
oral typical neuroleptics,
(62) possibly as a result of ensured drug 
delivery. Long acting injectable drugs should not be given to ameliorate acute behavioural disturbances.
(b) Atypical antipsychotic drugs
As implied above, there are major advantages for many patients to 
be treated with the atypical antipsychotic drugs and it is generally Table 6.2.5.5  Oral dosing of antipsychotic drugs
Equivalent doses (mg/day) Starting dose Titration schedule Dose range (mg/day)
Chlorpromazinea100 15–50 mg BID-QID As clinically indicated 300–1000 (divided QD-QID)

Fluphenazineb2 0.5–10 mg/day (divided Q6–8 hours) As clinically indicated 5–20
Haloperidolc2 0.5–5 mg BID As clinically indicated 5–20
Loxapine 10 10 mg BID As clinically indicated 30–100Mesoridazine 50 150–400
Molindone 10 50–75 mg/day divided TID-QID As clinically indicated 30–100Perphenazine
d10 4–8 mg TID (8–16 mg BID-QID if hospitalized) As clinically indicated 16–64
Thioridazine 100 50–100 mg TID As clinically indicated 300–800Tiotixene 5 2 mg TID As clinically indicated 15–50Triﬂ  uoperazine 5 2–5 mg BID As clinically indicated 15–50
For elderly patients, or those with renal or hepatic problems, doses of drug may need to be reduced by one-half or more

a Short-acting IM formulation may be given 25–50 mg (may repeat after 1–4 hrs as required); may gradually increase dose up to 40 0 mg IM Q 4-6 hrs (maximum of 2000 mg/day) may be 
needed for severe cases
b Short-acting IM formulation may be given 2.5–10 mg/day in Q6–8 hr intervals; Depot IM formulation may be given 12.5–25 mg Q 3 weeks
c Short-acting IM formulation may be given 2–5 mg Q 1–4 hrs; Depot IM formulation may be given at approximately 10–20 times the stable oral dose Q 4 weeks
d Short-acting IM formulation may be given 5–10 mg Q 6 hrs (maximum of 30 mg/day)
Starting dose Titration schedule Dose range (mg/day)
Aripiprazolea10–15 mg daily As clinically indicated, every 2 weeks 10–30
Clozapine 12.5 mg QD-BID Increase by 25–50 mg/day until usual effective dose of 300–450 mg/day after 2–4 weeks 150–600Olanzapine

b5–10 mg daily As clinically indicated, by 5 mg/day every 7 days 10–30
Paliperidone 6 mg/day As clinically indicated, by 3 mg/day Q 2–4 week increments, up to 12 mg daily 6–12Quetiapine 25 mg BID Increase by 25–50 mg BID-TID on days 2 and 3, to target dose of 300–400 mg daily 
 (QD – TID) by day 4. Further increases as clinically indicated by 25–50 mg BID every 2 days.300– 800
Risperidone
c 0.5–1 mg BID Increase by 0.5–1 mg BID on days 2 and 3, with further dose increases thereafter by 0.5–1 mg 
 increments Q 7 days as required2–8
Ziprasidoned20 mg BID with food Increase by 20–40 mg BID every 2 days to target dose of 80 mg (all doses with food) 120–200
For elderly patients, or those with renal or hepatic problems, doses of drug may need to be reduced by one-half or more, and ti tration may be slower

a Short-acting IM formulation may be given at 9.75 mg, though the lower 5.25 mg dose may be indicated in some situations.
b Short-acting IM formulation may be given 10 mg as required (may be repeated after 2 hrs, up to 30 mg/day).
c Long-acting IM formulation may be initiated at 25 mg Q 2 weeks (continue oral risperidone dose for 3 weeks), with increases as  clinically indicated every 4 weeks up to a dose of 50 mg Q 
2 weeks
d Short-acting IM formulation may be given 10–20 mg as required (may be repeated Q 2–4 hrs as needed, up to 40 mg/day)

1215
recommended that, where possible, these agents be considered as 
the ﬁ  rst-line treatment.(63, 64) The atypical antipsychotic drugs are 
the dominant antipsychotic treatment for schizophrenia, mania, and psychotic depression in clinical practice in many parts of the world. However, there is considerable international variation in their usage. Cost factors may explain part of the variance in the use of these agents within and between countries. The typical neuro-leptic drugs are no longer covered by patent protection and are avail-able in inexpensive generic forms. There are a number of patients whose psychosis is adequately controlled by these agents and they (and their families and prescribers) are content to continue them even when informed of the potential advantages of the newer anti-psychotic agents. When only the cost of medication is considered, it may seem that ﬁ  scal reasons argue for continuation of typical

neuroleptic drug treatment since the atypical agents can cost up to 
100 times more. In addition, the widely accepted notion of greater 
overall beneﬁ  t from treatment with atypical antipsychotic drugs, as 
opposed to typical neuroleptics, was recently challenged by results from two effectiveness studies. The ﬁ  rst of these demonstrated no 
signiﬁ  cant difference in all-cause discontinuation from the study as 
the primary endpoint, as well as discontinuation for lack of efﬁ  ca-
cy, between atypical drugs, with the exception of olanzapine, and the typical neuroleptic perphenazine.
(65) The latter study reported 
a lack of signiﬁ  cant differences in quality of life between patients 
who received naturalistic treatment with typical or atypical antipsy-chotic drugs.
(66) Methodological limitations, detailed discussion of which is beyond the scope of this chapter, limit the conclusions

(66) Methodological limitations, detailed discussion of which is beyond the scope of this chapter, limit the conclusions 
that can be drawn from these reports about the relative merits of one class of antipsychotics versus another, both of which are in dis-agreement with the majority of the clinical literature that docu-ments differences between these broad classes of antipsychotic drugs across a wide range of outcomes. Because medication costs account for, at most, 5 per cent of the total costs of schizophrenia, with the major costs being hospitalization and indirect costs such as lost income and disability income to support patients in the community, more effective and tolerable medications may offset their greater cost.
(67,68) As such, atypical antipsychotic drugs are 
recommended as ﬁ  rst line treatments of schizophrenia and related 
psychotic disorders. Each will be discussed separately.
(i) Clozapine

Clozapine was synthesized in 1959 as part of a project to discover antipsychotic drugs with low potential for extrapyramidal side-effects. It proved to be one of the most interesting and clinically important compounds ever discovered. It was labelled as atypical because of its ability to block amphetamine-induced locomotor activity, one of the most widely accepted models for antipsychotic activity, without producing catalepsy in rodents, the leading model for causation of extrapyramidal side-effects in humans. Subsequent clinical studies showed it to have the lowest extrapyra-midal side-effects of any antipsychotic drug known.
(5,69) Clinical 
trials in the 1960s and 1970s suggested it was also superior in Table 6.2.5.6  Target signs and symptoms for the pharmacological management of schizophrenia

Target Description
Positive syndrome Hallucinations
Delusions◆ Typically the most amenable to treatment with all antipsychotic drugs
Negative syndrome Avolition
Apathy
Anhedonia
Lack of responsiveness
Poor rapport with others
Passive social withdrawalPoverty of speech
Affective ﬂ  attening◆ Robustly correlated with functional impairment in schizohprenia
◆  More difﬁ  cult to treat pharmacologically, and may required longer to respond than 
positive signs and symptoms
◆ Pharmacological adjuncts may be needed, though under-studied
◆  Atypical antipsychotic drugs are believed to be more efﬁ  cacious than typical 
neuroleptics
Hostility/excitement Verbal or physical aggression ◆ Typically amenable to treatment with all antipsychotic drugs
◆ Use of parenteral formulation may be required

Mood and anxiety symptoms Depressed mood
Anxious mood
Nervousness
Panic symptomsSuicidal ideation◆ Believed to be more responsive to treatment with atypical antipsychotic drugs
◆  Clozapine has demonstrated superiority for treating chronic suicidality in 
Cognitive impairment 
(psychopathological deﬁ  nition)Disorientation
Problems with abstraction
Attentional problems
PreoccupationsDisorganized thought processes◆  Some domains respond favourably to antipsychotic drug treatment, though response 
is often incomplete
(neuropsychological testing 
deﬁ  nition)Working memory
Attention/vigilance
Verbal learning/memoryVisual learning/memory
Problem solving
Processing speed◆  Neuropsychological deﬁ  cits, like negative signs and symptoms, are robustly correlated

Processing speed◆  Neuropsychological deﬁ  cits, like negative signs and symptoms, are robustly correlated 
with functional outcome in schizophrenia
◆ Very difﬁ  cult to treat with medication alone
◆  Atypical antipsychotic drugs are believed to be superior to typical neuroleptics, 
though effect sizes are only mild to moderate for the former6.2.5 antipsychotic and anticholinergic drugs

SECTION 6  treatment methods in psychiatry 1216
efﬁ cacy with regard to control of positive symptoms, but given the 
standards of clinical trials of that era, these conclusions could not be relied upon.
(70) In 1975, 6 years after its introduction in Europe, 
clozapine’s ability to cause granulocytopenia or agranulocytosis 
was ﬁ  rst reported. Six deaths occurred in clozapine-treated patients 
in a geographically restricted area of Finland over a short period of time. The role of clozapine in these deaths is still uncertain because no other such clustering has ever occurred in Finland, or elsewhere. Nevertheless, clozapine was withdrawn from general use, although it remained available for humanitarian use in patients who had previously received it, for individual cases where it seemed indi-cated because of its low potential for extrapyramidal side-effects, and for research purposes.
(69)
Clozapine was reintroduced in 1989 after it was demonstrated to

(69)
Clozapine was reintroduced in 1989 after it was demonstrated to 
be superior to chlorpromazine to improve positive and negative symptoms in 300 patients who were resistant to the action of at least three typical neuroleptics.
(71) Thirty per cent of the patients 
treated with clozapine responded after 6 weeks of treatment compared to 4 per cent of the chlorpromazine-treated patients. Subsequent studies have shown that up to 60 to 70 per cent of patients will respond within 6 months of treatment. Patients with shorter duration of illness tend to respond better. Some predictors of response include weight gain and absence of atrophy in the prefrontal cortex.
(52) Clozapine has been reported in several stud-
ies to reduce the risk of suicide.(52, 72)  It has been shown in a large 
number of studies to improve some aspects of cognitive function, especially verbal ﬂ  uency, immediate and delayed verbal learning 
and memory, and attention.
(16–18)

(16–18)
Because of the side-effect proﬁ  le of clozapine, it is not generally 
used as a ﬁ  rst-line drug. On the other hand, monitoring the 
white blood count for the development of agranulocytosis or gran-ulocytopenia, as well as improved methods of treating agranulocy-tosis, have made it much safer to use. Clozapine is still probably underutilized in many parts of the world. Any patient with an unsatisfactory response to the typical neuroleptics and at least one atypical antipsychotic should be considered for clozapine treatment. This amounts to at least 20 per cent of schizophrenics. Clozapine use may also be considered for patients with schizophre-nia who are at high risk for suicide, even if the aforementioned threshold of inadequate response to other drugs has not yet been met.

Clozapine is usually given twice daily, but sometimes more than 
half of the dose or the entire dose is given at sleep time to minimize 
daytime sedation. The daily dosage is gradually titrated to the tar-get range described in Table 6.2.5.5. Patients who are treatment resistant may require higher doses. Typical or non-clozapine atypi-cal antipsychotic drugs should be discontinued either before begin-ning clozapine or by eliminating them over a 1- to 2-week period as the dose of clozapine is increased. Because clozapine produces only about 40 to 50 per cent occupancy of striatal D
2-receptors,(73)
and some of its key advantages are believed to be related to its low D
2-receptor blockade, concomitant administration of typical neu-
roleptic drugs would be predicted to interfere with some of the beneﬁ  ts of clozapine and, thus, should not ordinarily be prescribed

roleptic drugs would be predicted to interfere with some of the beneﬁ  ts of clozapine and, thus, should not ordinarily be prescribed 
with clozapine. However, some patients with persistent positive symptoms despite an adequate trial of clozapine monotherapy might be expected to beneﬁ  t from the addition of low-dose halo-
peridol, or its equivalent, to provide additional low level D
2-receptor 
blockade.Determination of clozapine plasma levels is useful whenever 
patients are not responding adequately. If response is inadequate, various approaches to augment response have also been utilized. In addition to adding a low dose of a typical neuroleptic, as men-tioned above, it may be useful to augment clozapine treatment with valproic acid or other mood stabilizer (such as lithium, carba-mazepine, lamotrigine or topiramate), anxiolytic drugs, or an antidepressant.
(52) The choice of augmenting agent is largely

(52) The choice of augmenting agent is largely 
driven by symptomatic considerations, or pharmacokinetic inter-actions in the case of ﬂ  uvoxamine. However, none of these strate-
gies have strong empiric support. One exception may be the addition of sulpiride, which may result in a signiﬁ  cant reduction in 
symptom burden when added to clozapine.
(74)Electroconvulsive 
therapy (ECT) also resulted in a modest further reduction in symptoms when used in conjunction with clozapine, and appears to be well tolerated.
(75) It is difﬁ  cult to postulate a rationale for

(75) It is difﬁ  cult to postulate a rationale for 
adding another atypical antipsychotic, with the exception of amis-ulpride, because of their similarity in pharmacology to clozapine. It should be discontinued if side-effects are intolerable, or if there is no apparent response after a 6-month trial of clozapine alone and subsequent trials with augmentation therapy. Clearly, further studies involving clozapine partial- or non-responders are urgently needed. It should be noted that discontinuation of clozapine can precipitate a severe relapse even when clozapine is slowly tapered.
(76)
(ii) Risperidone
Risperidone is useful as a ﬁ  rst-line drug for the treatment of all 
forms of schizophrenia, including residual schizophrenia.(77–79)
Deﬁ nitive data are lacking for its efﬁ  cacy in patients who are

Deﬁ nitive data are lacking for its efﬁ  cacy in patients who are 
neuroleptic resistant or who have failed to respond to other atypical antipsychotics, including clozapine.
(80) Clinical experience 
is not supportive of widespread efficacy in these groups but there may be some responders. However, risperidone may be useful in patients who fail to tolerate other antipsychotic agents because of side-effects not shared by risperidone, such as anticholinergic effects. Risperidone is well-tolerated in low doses by the elderly and has been widely used in the United States for the treatment of a variety of senile psychoses.
(81, 82)  Its efﬁ  cacy against haloperi-
dol was established in a series of multicentre trials which demon-strated advantages for risperidone in overall psychopathology in mainly chronic schizophrenic patients in an acute exacerbation at doses in the 6 to 8 mg/day range.
(11, 77)  However, these doses

(11, 77)  However, these doses 
have proven to be higher than is needed for most patients in clinical practice, possibly reflecting some of the problems in generalizing from controlled clinical trials. The doses for schizo-phrenia most often used in non-elderly adults are now 4 to 6 mg/day. First-episode patients may not tolerate higher doses (e.g. above 5 mg per day), and some may respond to as little as 1 to 2 mg/day. Some treatment-resistant patients may need doses higher than 6 mg/day; however, the results of clinical studies in this population have been mixed. Whether prolonged trials, i.e. up to 6 months, are useful in such patients, as they are in clozapine patients, is not yet known.
Beyond treatment of acute symptoms, the position occupied 
by risperidone as a ﬁ  rst line treatment option is also supported 
by long term maintenance phase and relapse prevention studies.

by long term maintenance phase and relapse prevention studies. 
For instance, relative to haloperidol, risperidone has also been associated with a lower risk of relapse (34 vs. 60 per cent) over a

1217
minimum of 12 months of treatment.(83) In another study that 
|retrospectively compared rates of rehospitalization for patients who received treatment with risperidone, olanzapine, or typical neuroleptics, rehosptialization rates for risperidone and olanzapine were similar, and both were signiﬁ  cantly less than those of patients 
treated with typical neuroleptics.
(84)
Risperidone is usually initiated at low doses (e.g. 1–2 mg daily) 
and is titrated into the dosage range provided in Table 6.2.5.5. The medication is often initiated in twice daily dosing; however, because its primary active metabolite, 9-OH risperidone, is phar-macologically equivalent to its parent drug and because it has a longer elimination half-life, once daily dosing is also possible. Risperidone is available in soluble wafer and liquid forms, which may be advantageous for patients who have swallowing difﬁ  culties

or require taking their medication in a non-pill form for other rea-sons, including their own preference.
For patients who have a history of poor compliance leading 
to frequently relapsing illness, or for those who prefer it, a long acting injectable form of risperidone is available (Table 6.2.5.1) for administration typically every two weeks. For treatment 
responsive patients, response may be expected to occur in the 
25–50 mg (per every two week dose) range,
(85) however, oral 
risperidone must be continued through at least the ﬁ  rst 3 weeks 
of treatment with the long acting injectable form before being slowly tapered. Supplementation with oral medication may be required when the dose of the long-acting drug is upwardly adjusted due to breakthrough psychotic symptoms. As is the case with long-acting injectable typical antipsychotics, long-acting injectable risperidone should not be used acutely to control dangerous behaviours.

Risperidone has more of a tendency to produce extrapyramidal 
side-effects than any of the other atypical antipsychotics but this can be minimized by using the lowest dose which controls positive symptoms and adding an anticholinergic drug, if necessary.
(82)
Addition of a typical neuroleptic to risperidone will increase the risk of extrapyramidal side-effects. Risperidone is not well tolerat-ed by patients with Parkinson’s disease because of extrapyramidal side-effects. There are some data suggesting the risk of tardive dyski-nesia in patients with schizophrenia, and especially the elderly, with risperidone is less than that of the typical neuroleptic drugs.
(86)
Among atypical antipsychotic drugs, risperidone and paliperi-
done appear to be the most liable in terms of increasing prolactin release. As is the case with EPS, the effect of risperidone on prolac-tin concentration appears to positively correlate with dose.
(25) The

(25) The 
changes may occur in both men and women; however, the greatest elevations appear to occur among women. Elevations in prolactin levels as a result of treatment with risperidone do not always trans-late into clinical symptoms such as sexual dysfunction or gynaeco-mastia in men and menstrual changes and breast discharge 
in women; however, patients should be monitored clinically for 
these effects, and prolactin concentrations measured if these symptoms occur.
The issue of whether the improvement in negative symptoms 
by risperidone and other atypical antipsychotic drugs is due to an effect on so-called primary negative symptoms versus secondary negative symptoms has been much debated. Data from large multicentre trials of risperidone versus clozapine show an effect on primary negative symptoms as residual change left after adjusting for improvement due to decreases in positive or depressive symptoms and extrapyramidal side-effects.
(87) In addition, results

(87) In addition, results 
from a meta-analysis of 6 studies comparing risperidone to typical neuroleptic treatment indicated greater response rate for negative symptoms (deﬁ  ned as achieving >20 per cent reduction in negative 
symptom burden) as well as greater reduction in anxious/depres-sive symptoms among risperidone treated patients.
(88) Risperidone 
has a greater ability to improve cognition in schizophrenia than the typical neuroleptic drugs.
(17) Improvement in working memory 
has been the strongest ﬁ  nding, while improveme nts in attention, 
executive function, and verbal learning and memory have also been reported. Risperidone has been shown to be a cost-effective treatment for schizophrenia,
(89) especially in its long-acting 
injectable form,(90)and to improve quality of life,(91) ﬁ rm conclu-
sions about relative cost-effectiveness between atypical antipsy-chotic drugs for non-treatment-resistant schizophrenia are difﬁ  cult

sions about relative cost-effectiveness between atypical antipsy-chotic drugs for non-treatment-resistant schizophrenia are difﬁ  cult 
to draw at this time. Further research in this important area is needed.
In summary, risperidone is a ﬁ  rst line pharmacological treatment 
of schizophrenia and other forms of psychosis. It may produce sig-niﬁ cant advantages over typical neuroleptic drugs with regard to 
negative symptoms, cognition, and extrapyramidal side-effects, but it does produce dose dependent increases in EPS risk, and increases in serum prolactin levels resembling those of typical antipsychotic drugs. It should be used at the lower doses where possible. A long-acting injectable form of this medication should be considered a ﬁ rst line treatment option in cases of frequent relapse due to poor 
medication compliance.
(iii) Olanzapine
Olanzapine is indicated as a ﬁ  rst-line treatment for all forms of 
schizophrenia(63, 92)  with the caveat that it has not been shown to be

schizophrenia(63, 92)  with the caveat that it has not been shown to be 
as effective as clozapine in neuroleptic-resistant patients at conven-tional doses.
(8, 60) However, some patients of this type do respond to 
olanzapine,(93) perhaps at high doses.(94, 95)  There are no means 
yet to determine which of this group of patients will respond to olanzapine (or risperidone) so some clinicians may elect a trial with either of these agents before considering clozapine.
The efﬁ  cacy of olanzapine in treating psychosis and negative 
symptoms in patients with an acute exacerbation of schizophrenia has been ﬁ  rmly established in a variety of large-scale, multicentre 
trials.
(92) In these trials, olanzapine at doses of 10 to 20 mg/day has

trials.
(92) In these trials, olanzapine at doses of 10 to 20 mg/day has 
been superior to placebo and equivalent or superior to haloperidol in some measures of total psychopathology, positive, or negative symptoms. For example, in the North American multicentre trial, high-dose olanzapine (15 ± 5 mg/day) was superior to haloperidol (15 ± 5 mg/day) in the treatment of negative symptoms.
(96) The 
effect of olanzapine to improve negative symptoms was found to be on primary rather than secondary negative symptoms.
(97)
Olanzapine has also been found to be effective as a maintenance 
treatment of schizophrenia.(98) The estimated relapse rates, deﬁ  ned 
as the need for hospitalization, during a 1-year period in three studies of patients receiving olanzapine for maintenance treatment were 19.6 to 28.6 per cent. These rates were signiﬁ  cantly lower 
than those in patients receiving placebo, ineffective doses of olanzapine, or haloperidol.
(98) Olanzapine has some efﬁ  cacy in

(98) Olanzapine has some efﬁ  cacy in 
treating anxious and depressive symptoms,(99) as well as cognitive 
dys function,(17, 18) associated with schizophrenia or schizoaffective 
disorder. Pharmacoeconomic studies and investigations of medica-tion effects on quality of life measures indicate that olanzapine has 6.2.5 antipsychotic and anticholinergic drugs

SECTION 6  treatment methods in psychiatry 1218
a beneﬁ  cial cost-outcome proﬁ  le. For instance, in one investigation, 
the higher cost of olanzapine relative to haloperidol was offset by olanzapine-treatment associated reductions in rehospitalization and overall treatment costs.
(100) Olanzapine treatment has also 
been associated with better outcomes as assessed by overall and 
health-related quality of life relative to haloperidol.(101)As 
mentioned above, olanzapine was found to be the most effective antipsychotic drug in the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) phase I study.
(65)
The average clinical dose of olanzapine is 12.5 to 20 mg/day but 
many patients may be expected to respond to lower doses (e.g. 10 mg daily).
(102) A principle advantage of olanzapine is its once

(102) A principle advantage of olanzapine is its once 
daily dosing and the feasibility of starting the medication at a dose that is clinically effective for most patients. Doses higher than 20 mg/day are rarely more effective than lower doses, especially for non-refractory cases. Augmentation of olanzapine with typical neuroleptic drugs or risperidone should be done sparingly to avoid extrapyramidal side-effects and possibly compromising efﬁ  cacy. 
Olanzapine is also available in a soluble wafer form that may be preferred to the pill form by some patients, especially those with swallowing difﬁ  culties and related problems.
For acute situations where rapid control of agitation, hostility or 
other dangerous behaviours is required, olanzapine is available as a short-acting injectable medication (Table 6.2.5.1).
(103) Similar to

(103) Similar to 
short-acting typical neuroleptic drugs, the medication is delivered intramuscularly. Doses of 5 to 10 mg per injection may be given, depending on the severity of the target behaviours. A long-acting formulation is in clinical testing.
In summary, olanzapine has found wide acceptance as an atypi-
cal antipsychotic drug because of its once-a-day administration, efﬁ cacy for negative symptoms, improvement in cognitive func-
tion, and low extrapyramidal side-effect proﬁ  le. Signiﬁ  cant weight 
gain and other metabolic effects may be a problem for some patients, as will be discussed below.
(iv) Quetiapine
Quetiapine has been shown to be as effective as typical antipsy-chotics, with fewer extrapyramidal side-effects and no effect on serum prolactin levels.
(104,105)  Part of the reason for this may be

(104,105)  Part of the reason for this may be 
that quetiapine and clozapine both appear to bind more loosely to striatal D2 receptors than other antipsychotic drugs, and that both drugs show antipsychotic activity at D2 receptor occupancies that are well below the 60 per cent threshold identiﬁ  ed for most other 
antipsychotic drugs.
(106) In spite of this similarity with clozapine, 
quetiapine does not appear to have efﬁ  cacy comparable to clozap-
ine for treatment-resistant patients.
The efﬁ  cacy of quetiapine for acute phase schizophrenia is sup-
ported by results from several randomized, controlled trials that documented superiority of quetiapine relative to placebo across several doses, with some patients with some patients responding to 150 mg/day and others requiring 750 mg/day.
(104) For instance, in

(104) For instance, in 
one high- (750 mg/day) versus low-dosage (250 mg/day) study, both dosage groups evidenced greater reduction in positive symp-toms relative to placebo; however, the differences were signiﬁ  cant 
only for the high-dose group.
(105) In another study that assessed 
multiple ﬁ  xed doses of quetiapine (75 to 750 mg/day) compared 
with haloperidol and placebo, signiﬁ  cant differences in improve-
ment over placebo for quetiapine were observed in the dosage range of 150 to 750 mg/day.
(104)Quetiapine’s effect on negative symptoms continue to be investi-
gated. One placebo controlled comparison documented improve-ments in negative symptoms with quetiapine treatment across a wide range of doses, with the greatest improvement reported at 300 mg daily.
(104) In the high- vs. low- dose study reviewed above, 
the high-dose group also experienced greater improvement in negative symptoms relative to placebo.
(105) Like risperidone

(105) Like risperidone 
and olanzapine, quetiapine appears to improve depressive symptoms
(107) and certain cognitive deﬁ  cits(17,18)  associated with 
schizophrenia or schizoaffective disorder. The improvements in cognition with quetiapine appear to be superior to those of halo-peridol.
(108)
These results suggest that, overall, the greatest improvement in 
positive and negative symptoms may occur when quetiapine is used at the higher end of its dosage range. The average clinical dose appears to be between 300 and 500 mg/day, usually given twice daily though some beneﬁ  t from the medication when given only

once daily. The effects of using higher doses for patients who do not respond adequately to these doses are uncertain. A titration of the dosage is required after initiating the medication. From the viewpoint of EPS and hyperprolactinaemic effects, quetiapine appears to confer only low risk. As such, it, like clozapine, appears to be well tolerated even among patients with idiopathic Parkinson’s disease.
(109) Sedation may be a limiting side effect for some, espe-
cially during dosage titration. Weight related, metabolic, and other adverse effects will be discussed in greater detail below.
In summary, quetiapine also appears to be effective for a wide 
range of schizophrenia-associated symptoms and confers a lower level of risk in terms of antidopaminergic adverse effects. The dosage range of this medication may be quite wide, though patients may have a greater chance of beneﬁ  ting from the medication at the 
higher end of this range.
(v) Ziprasidone

Ziprasidone has a varied receptor occupancy proﬁ  le. Like most 
atypical antipsychotic drugs, it displays high afﬁ  nity 5-HT2A bind-
ing coupled with relatively lower afﬁ  nity D2 receptor binding. 
Ziprasidone is also a 5-HT1A agonist, as well as both a serotonin and norepinephrine reuptake pump inhibitor.
(110) This proﬁ  le 
predicts a wide range of pharmacological activity against core psychotic symptoms, negative and affective symptoms, as well as neurocognition.
Ziprasidone, like quetiapine, has been shown to be superior to 
placebo for the reduction of total psychopathology and positive and negative symptoms.
(111,112)  There is limited evidence to suggest 
superiority over typical neuroleptics with regard to improvement in positive and negative symptoms.
(111,113)  Studies of multiple ﬁ  xed 
doses of ziprasidone vs. haloperidol at conventional doses indicate that ziprasidone yields similar efﬁ  cacy to haloperidol for reducing

doses of ziprasidone vs. haloperidol at conventional doses indicate that ziprasidone yields similar efﬁ  cacy to haloperidol for reducing 
positive symptoms and global psychopathology at a dose of 160 mg/day.
(113) Doses greater than 160 mg/day have not been system-
atically investigated.
Ziprasidone significantly improved negative symptoms and 
reduced the risk of relapse compared to placebo in a 1-year mainte-nance study in stable hospitalized chronic schizophrenic patients.
(114) These maintenance phase effects were not dependent 
on the daily dose of ziprasidone. In a 28-week comparison with haloperidol, the two groups evidenced similar overall effects for positive symptoms; however, between groups differences were

1219
documented favouring ziprasidone for negative symptoms and 
EPS.(115) Ziprasidone was effective against depressive symptoms 
associated with schizophrenia in one study at a dose of 160 mg/day.
(116) Signiﬁ  cant improvements in multiple cognitive domains 
have been reported among ziprasidone treated patients in a variety 
of treatment contexts.(117) Such changes appear to be unrelated to 
improvements in other symptoms of schizophrenia. Ziprasidone treatment has been associated with significant improvement in quality of life measures in one post hoc data analysis.
(118) Further 
investigation of the effect of ziprasidone on health related quality of life and similar outcomes are warranted. Ziprasidone treat ment of schizophrenia appears to be cost-effective relative to no treatment.
(119) Further cost-beneﬁ  t studies are needed.
The dose range of ziprasidone for acute treatment appears to

The dose range of ziprasidone for acute treatment appears to 
be between 80 and 160 mg/day, higher doses within this range may be more effective (Table 6.2.5.5). Doses greater than 120 mg/day appear to be required to achieve >60 per cent dopamine D2 
receptor blockade,
(120) the D2 receptor occupancy threshold that 
appears to coincide with efﬁ  cacy against positive symptoms, as pre-
sented earlier. The medication is usually given twice daily, although some may take the medication once daily at night time. A titration of the total daily dose into the recommended range is required after initiating the medication. One critical aspect of medication administration for ziprasidone is the requirement that the medica-tion be taken with food. There appear to be profound differences in bioavailability at equivalent doses between the fed and unfed state.
(121) A full meal, as opposed to a light snack, appears to be

(121) A full meal, as opposed to a light snack, appears to be 
required. Therefore, patients are encouraged to take their medica-tion with meals.
A short-acting intramuscular formulation of ziprasidone has 
been developed which should be useful in situations where more rapid action is needed. This formulation is available in two doses (10 and 20 mg), the preferred dosage being 20 mg due to signiﬁ  -
cantly greater reduction in agitation relative to lower dose.
(122) The 
use of the short-acting injectable form can facilitate a transition to oral medication, and may reduce that time required to titrate the daily dose of ziprasidone to one that is likely to be effective.
Ziprasidone appears to be well tolerated. Treatment-emergent 
EPS burden is low.
(112,113) Initial problems with somnolence or

(112,113) Initial problems with somnolence or 
behavioural activation are usually self limited, although temporary use of clonazepam or other benzodiazepine at low doses may improve tolerability, especially during the titration phase, should the latter occur. Importantly, data from both short- and long-term studies indicated that ziprasidone is not associated with clinically signiﬁ  cant changes in weight, glycaemic measures, or markers of 
lipid homeostasis.
(123)
Ziprasidone can result in partial blockade of the slow potassium 
rectiﬁ  er current in the cardiac conduction system, which may result 
in prolongation of the QTc interval (discussed in greater detail 
below).(124)On the other hand, there is only one case report of 
ziprasidone induced torsades de pointes , the risk of which is believed 
to be increased if the QTc interval is >500 msec.(125) There

to be increased if the QTc interval is >500 msec.(125) There 
have also been no reported deaths in the context of overdose with the medication. Under routine circumstances, screening electro-cardiograms are not required. Nevertheless, caution may be warranted for individuals who are at risk for signiﬁ  cant prolonga-
tion of the QTc, including patients who take medications other than ziprasidone that prolong the QTc. Concomitant use of CYP-450 3A4 inhibitors does not appear to pose a signiﬁ  cant risk.
(126)In summary, ziprasidone appears to be a useful additional 
atypical antipsychotic agent because of its favourable side-effect proﬁ le, including no weight gain—a major problem with olanzapine

atypical antipsychotic agent because of its favourable side-effect proﬁ le, including no weight gain—a major problem with olanzapine 
and clozapine-and no prolactin elevation, which is a less serious side-effect of risperidone. Patients should be instructed to take the medication with food. Ziprasidone treatment may result in an increase in the QTc interval; however, in a great majority of cases, this is not clinically signiﬁ  cant.
(vi) Aripiprazole
Among the atypical antipsychotics, aripiprazole is pharmacologi-
cally unique in that it combines partial D2 receptor agonism with high potency 5-HT2A antagonism. Because it is a partial D2 recep-tor agonist, it binds to the receptor with full afﬁ  nity, but exerts only

a fraction of the intrinsic activity at that site that would be expected of endogenous dopamine. As such, in states of relative dopamine excess, as is believed to be the case in the ventral striatum among schizophrenic patients who experience positive symptoms, aripiprazole is believed to exert relative antagonist activity at D2 receptors.
(127) Conversely, it is believed to act primarily as an ago-
nist in cases of relative hypo-dopaminergia, as may be the case in the prefrontal cortex in patients with schizophrenia.
(22) For this 
reason, aripiprazole and other D2 partial agonists in development are sometimes referred to as ‘dopamine stabilizers.’ Aripiprazole also functions as a potent 5-HT1A partial agonist.
(128)
The efﬁ  cacy of aripiprazole in the treatment of acute schizophre-
nia at doses ranging between 10 and 30 mg (taken once daily) was established on the basis of four short-term randomized controlled studies.
(129) Relative to placebo, efﬁ  cacy against negative symptoms

(129) Relative to placebo, efﬁ  cacy against negative symptoms 
was also demonstrated.(130) Long term superiority of aripiprazole 
(vs. placebo) for relapse over 26 weeks(131) and medication compli-
ance and symptom response (vs. haloperidol) for up to 52 weeks has also been established.
(133) One study reported on the effective-
ness of ﬂ  exibly dosed aripiprazole (15–30 mg daily) among patients 
with schizophrenia with a history of resistance to treatment with olanzapine or risperidone.
(133) The utility of aripiprazole in the 
setting of well deﬁ  ned treatment refractory schizophrenia requires 
further systematic investigation.
The overall effectivenss of aripiprazole has been evaluated in two 
recent studies. One study reported the effectivenss of ﬂ  exibly dosed 
aripiprazole over 8 weeks of treatment (53 per cent response rate at mean endpoint dose = 19.9 mg/day) among a cohort of patients

aripiprazole over 8 weeks of treatment (53 per cent response rate at mean endpoint dose = 19.9 mg/day) among a cohort of patients 
with chronic schizophrenia and schizoaffective disorder under rou-tine treatment conditions in a community healthcare setting.
(134)
The second study documented comparable effectiveness with olan-zapine over 52 weeks of treatment, with more favourable effects for aripiprazole for several metabolic adverse effects.
(135) As is the case 
with other atypical antipsychotic drugs, early evidence indicates that aripiprazole may also have beneﬁ  cial effects on neurocognitive 
performance in patients with schizophrenia at recommended doses.
(136) Further study of the effects of this medication on cogni-
tion is indicated. Clinically relevant improvement in quality of life has been documented in one study.
(137) More cost-outcome studies 
of aripiprazole are needed.
Treatment with aripiprazole is usually initiated with 10 to 15 mg

Treatment with aripiprazole is usually initiated with 10 to 15 mg 
daily, although some patients may not be able to tolerate these doses due to agitation, nausea or vomiting. The dose can be increased up to 30 mg if needed, and tolerated. An oral solution form is also available. Aripiprazole is also available in a soluble 6.2.5 antipsychotic and anticholinergic drugs

SECTION 6  treatment methods in psychiatry 1220
wafer as well as an acute intramuscular form. The acute injectable 
form appears to be effective in the dosage range of 5.25 to 15 mg.(138)
The recommended dose is 9.75 mg.
Aripiprazole is generally well tolerated, with an adverse effect 
proﬁ le similar to placebo in short-term studies involving patients 
with acute schizophrenia and in longer-term studies of chronic, 
stable patients.(129) As is the case with all atypical antipsychotic 
drugs, the EPS burden is lower than that of typical neuroleptics. Some patients, however, may encounter this effect if the dose is started too high or if the titration is too aggressive. Aripiprazole treatment does not appear to signiﬁ  cantly increase, and may cause 
a slight decrease, in prolactin levels.
(25) Importantly, short- and 
longer-term studies indicated that, similar to ziprasidone, aripipra-zole is not associated with a high risk of signiﬁ  cant changes in

longer-term studies indicated that, similar to ziprasidone, aripipra-zole is not associated with a high risk of signiﬁ  cant changes in 
weight, glycaemic measures, or markers of lipid metabolism.
(123)
In summary, aripiprazole appears to be effective as an acute and 
long-term maintenance treatment for schizophrenia and related psychotic disorders at recommended doses, though some patients may require higher doses. Aripiprazole was initiated in most studies at doses of 10 to 15 mg once daily; however, some patients may require a slower titration following a lower starting dose. This medication is available in many dosing forms, all of which appear to be very well tolerated. Important beneﬁ  ts from a tolerability 
viewpoint include very low rates of prolactin elevation, and low risk of weight gain and metabolic adverse effects.
(vii) Paliperidone

Paliperidone is the most recent antipsychotic drug to gain approval for use in the US. It is the 9-OH metabolite of risperidone, which has a longer elimination half-life than the parent compound, as reviewed above. Additionally, paliperidone, which is pharmacologi-cally similar with regard to receptor occupancy proﬁ  le to risperidone, 
is available commercially in an extended release form.
The short-term efﬁ  cacy of paliperidone has been established on 
the basis of three randomized, placebo controlled studies, two of which have been published,
(139,140) that investigated the clinical 
efﬁ cacy of 5 ﬁ  xed doses (3, 6, 9, 12, and 15 mg) given once daily

efﬁ cacy of 5 ﬁ  xed doses (3, 6, 9, 12, and 15 mg) given once daily 
relative to placebo. In each of these studies, all doses of paliperi-done were superior to placebo for reducing global psychopathology and positive symptoms, as well as negative symptoms, anxious/depressive symptoms associated with schizophrenia, and hostility/excitement. In addition, all doses of paliperidone were superior to placebo for improving measures of functional capacity. Paliperidone has not been investigated in the context of treatment refractory schizophrenia. Paliperidone appears to be effective for the preven-tion of relapse on the basis of one published study.
(141)
The recommended starting dose of paliperidone in its extended

(141)
The recommended starting dose of paliperidone in its extended 
release form is 6 mg, given once daily. Even though there is a suggestion of greater improvement in terms of symptom reduction from the paliperidone registration studies at higher doses, the adverse effect burden may also be greater (discussed below). Doses may be upwardly adjusted at 3 mg/day increments, up to 12 mg daily. Investigatons of doses greater than 6 mg daily for patients who do not respond adequately have not been performed. A long acting injectable form of paliperidone is currently in development.
Pooled analysis of data from the three short-term, acute phase 
studies indicate that paliperidone appears to be well tolerated, and that the recommended starting dose (6 mg once daily) was associ-ated with a placebo-like overall adverse effect proﬁ  le.
(142) At doses higher than 6 mg, there appeared to be an increase in the reported

(142) At doses higher than 6 mg, there appeared to be an increase in the reported 
incidence of EPS, though not to the degree at any of the doses test-ed that would be expected with typical neuroleptic treatment. Elevations in prolactin levels appear to be consistent with those observed with risperidone treatment, and appear to be greater in magnitude at higher doses. This effect appears to be especially pronounced among female patients. There were no signiﬁ  cant 
changes from baseline in weight or measures of lipid or glucose handling. Data from long term investigations will provide a more comprehensive picture of paliperidone’s tolerability proﬁ  le.
In summary, paliperidone, the newest atypical antipsychotic

In summary, paliperidone, the newest atypical antipsychotic 
drug, appears to be safe and effective for both short- and long-term treatment of schizophrenia. The EPS and prolactinemic adverse effect burden may resemble that of risperidone, but this notion requires prospective investigation. Paliperidone in its extended release form can be started at a clinically effective dose. A long-acting injectable form is currently in development.
(viii) Amisulpride
The efﬁ  cacy of amisulpride for the treatment of positive symptoms 
has been established over a wide dosage range (200 to 1200 mg daily) in treatment studies of up to 12 months duration.
(143)
In general, it appears that higher doses (above 400 mg/day) are effective for treating patients with predominately positive symp-toms, although efﬁ  cacy against negative symptoms has also been 
demonstrated in this dosing range.
(144, 145) Low-dose amisulpride 
(≤ 300 mg/day) has been shown to be effective in treating negative

(≤ 300 mg/day) has been shown to be effective in treating negative 
symptoms in schizophrenics with predominantly negative symptoms.
(146–148) Evaluation of the effect of amisulpride in 
patients with minimal extrapyramidal side-effects and positive symptoms suggests amisulpride is able to improve primary negative symptoms, even in patients with deficit syndrome schizophrenia.
(146–148)  At both dose ranges, amisulpride produces

(146–148)  At both dose ranges, amisulpride produces 
minimal extrapyramidal side-effects, but may result in increased prolactin levels. Amisulpride has been directly compared with hal-operidol, and with both risperidone and olanzapine. In general, amisulpride appears to be as clinically effective as all three drugs for treating positive symptoms. Improvement in negative symp-toms is superior to haloperidol and appear equivalent to olanzap-ine and risperidone. Improvement in depressive symptoms related to schizophrenia were also equivalent between amisulpride and olanzapine; however, in a meta-analysis of three studies, amisul-pride was shown to be superior to high dose risperidone (8 mg daily) and haloperidol.
(149) It is unknown if it is effective in 
neuroleptic-resistant patients. Because its pharmacology is quite distinct from that of the 5-HT
2A-based receptor antagonists previ-

ously discussed, amisulpride may be useful in patients who fail to tolerate that class of drugs. Amisulpride has also been demonstrated as being superior to haloperidol on quality of life measures and global functioning.
(150) Pharmacoeconomic analyses indicate that 
amisulpride has a beneﬁ  cial cost-outcome proﬁ  le.(151)
(c) Iloperidone and asenapine
Clinical trials are currently taking place with both of these atypical 
agent to determine its efﬁ  cacy and side-effect proﬁ  le compared 
with typical and other atypical antipsy chotic drugs. Like most other 
atypical antipsychotic drugs, both asenapine and iloperidone com-bine potent 5-HT2A antagonism with less potent D2 receptor antag-onism. Asenapine is currently undergoing investigation in phase 3

1221
clinical trials. Short-term, acute phase efﬁ  cacy of iloperidone for 
symptom reduction relative to placebo has been demonstrated at daily doses of 20 to 24 mg daily, with less certain effects at lower doses.
(152) Long-term investigations thus far indicate a low inci-
dence of EPS, lack of effect on prolactin release, and minimal effect 
on body weight.(152) It has the potential to be made into a long-
acting form, which would be of great value.
Pharmacokinetics, metabolism, and drug interactions
(a) Typical neuroleptics

The typical neuroleptics are well absorbed when administered orally or parenterally. Intramuscular injection leads to more rapid and higher plasma levels. Peak plasma levels are reached in 30 min after intramuscular injection and 1 to 4 h after oral injection. Steady state is achieved in 3 to 5 days. The half-life for elimination is in the range of 10 to 30 h. Substantial amounts of the antipsychotics are stored in lipids, including in the brain. There is controversy about how long these drugs persist in the system after discontinuation. By the criterion of elevations of plasma prolactin levels, the concen-trations are too low to be biologically active within 48 h after discontinuing oral medication. On the other hand, some rodent and human positron emission tomography studies suggest that long-acting forms of haloperidol or ﬂ  uphenazaine may persist for

1 to 3 months. Metabolism of the typical and atypical antipsychotic 
drugs occurs in the liver for the most part, via conjugation with glucuronic acid, hydroxylation, oxidation, demethylation and 
sulphoxide formation. Much of this metabolism occurs via the hepatic cytochrome (CYP)-450 enzymes, particularly the 2D6 and 3A4 sub-families for most drugs. Some metabolites have signiﬁ  cant 
biological activity, for example mesoridazine, and 7-hydroxyloxap ine. 
Dosing of typical neuroleptic medications are determined by clinical effects, less by pharmacokinetic factors.
Pharmacokinetic drug-drug interactions at the level of protein

binding are expected to be minimal, even though most typical neu-roleptics are tightly bound to plasma proteins. Even so, appropriate therapeutic monitoring of drugs that are also tightly bound to plas-ma proteins but have a narrow therapeutic index (e.g. warfarin, digoxin, phenytoin) when used in conjunction with typical neuro-leptics is warranted. Interactions at the level of the CYP-450 system are also thought to be minimal for most agents. Because smoking is so common among patients with schizophrenia and because smok-ing can be associated with potent induction of CYP-450 1A2 isoen-zymatic activity, dosage adjustments may be needed for selected antipsychotic drugs during any changes in smoking status. Other combinations with typical neuroleptics may be worth avoiding for other reasons, such as increased central nervous system affects (e.g. anxiolytics, other central nervous system depressants, anticholiner-gics, certain antihypertensive drugs), increased EPS (e.g. metoclo-pramide,

such as increased central nervous system affects (e.g. anxiolytics, other central nervous system depressants, anticholiner-gics, certain antihypertensive drugs), increased EPS (e.g. metoclo-pramide, D2 blocking anti-nausea drugs, caffeine), impaired cardiac

conduction (certain drugs combined with typical neuroleptics 
known to prolong the QTc interval), and neurotoxicity (lithium), 
especially among individuals who are more advanced in age.
There are wide variations in the pharmacokinetics of clozapine in 
patients. The average half-life is 6 to 12 h. Plasma concentrations are higher in Chinese patients than in Caucasian patients, in non-smokers than smokers, and in females than males. The bioavailability is not affected by food intake, metabolism occurs mainly in the 
liver. The chief metabolite is N-desmethylclozapine, which has

liver. The chief metabolite is N-desmethylclozapine, which has 
some biological activity. Clozapine is metabolized by CYP1A2, and several potential drug-drug interactions are thus possible. When agents that induce CYP-1A2 are prescribed or ingested, close monitoring of patients for a worsening of symptoms is warranted. Plasma levels of clozapine of approximately 350 ng/ml are more often associated with good response than lower levels,
(153) and 
should be checked in such cases. Upward adjustment of the clozap-ine daily dosage will typically correct the problem. On the other hand, if a CYP1A2 inducer is discontinued or a potent inhibitor is added, this may result in a rise in clozapine concentration, and an increase in adverse effect risk.
(154) Caution may also be warranted 
for drugs that are potent inhibitors of CYP 2C19 and CYP3A4.(155)

In addition, caution is warranted when considering concomitant use of drugs which can also cause bone marrow suppression (e.g. carbamazepine) or precipitously drop seizure threshold.
Risperidone is well absorbed from the gut and is extensively metab-olized in the liver by CYP2D6 to 9-hydroxyrisperidone in approxi-mately 92 to 94 per cent of Caucasians.
(156) Thus, 9-0H risperidone

(156) Thus, 9-0H risperidone 
is an active species in the majority of patients. About 6 to 8 per cent of Caucasians and a small proportion of Asians have a polymor-phism of the CYP2D6 gene, which leads to poor metabolism of risperidone. For poor metabolizers of risperidone, the active moi-ety is mainly the parent compound. The half-life of the 9-hydroxy metabolite is about 21 h whereas the half-life of risperidone is about 3 h. Thus, risperidone can be used on a once-a-day schedule for normal metabolizers whereas multiple doses are needed for those who are poor metabolizers. Risperidone should be titrat-ed from 2 to 5 mg/day over at least a 3-day period to minimize hypotensive  and neuro muscular side-effects. Drugs known to induce or inhibit CYP2D6 and 3A4 may alter plasma levels of risperidone; thus, close monitoring is advised when such agents are 
added to ongoing risperidone treatment.
Olanzapine has a half-life of 24 to 30 h, which indicates that single

Olanzapine has a half-life of 24 to 30 h, which indicates that single 
daily administration is adequate.(92) The metabolic pathways of 
olanzapine involves CYP2D6, CYP1A2 and flavin-containing mono-oxygenases, as well as N-glucuronidation. It has a low 
potential for drug-drug interactions and requires extremely high concentrations not likely to be achieved under clinical conditions to inhibit cytochrome P-450 systems. Plasma levels of approxi-mately 9.3 mg/ml have been reported to predict better clinical response to olanzapine in inpatients with an acute exacerbation.
(157)
Drugs that are known inducers or inhibitors of CYP1A2 may sig-niﬁ cantly affect plasma levels of olanzapine and alter its clinical 
effects at a given dosage; thus, active monitoring of symptoms and adverse effects is indicated if such agents are added. As is the case with clozapine, gender and smoking status may inﬂ  uence olanzapine

levels leading to adjustment in dosage.
(153)
Quetiapine is well absorbed and is approximately 83 per cent protein bound.
(158) Quetiapine is absorbed better after eating.(158)
It has a half-life of 6 h. It is metabolized in the liver by CYP3A4 to inactive metabolites. Quetiapine has signiﬁ  cant interactions with 
several inducers and inhibitors of CYP3A4. Co-administration with 6.2.5 antipsychotic and anticholinergic drugs

SECTION 6  treatment methods in psychiatry 1222
these agents may require dosage adjustment. Thioridazine may 
also signiﬁ  cantly increase the clearance of quetiapine,(159) thus 
necessitating dosage adjustment. Despite the short half-life, a clinical trial compared three dosing regimens (450 mg/day given in two or three divided doses, and 50 mg/day given twice daily). Both of the higher-dose groups were superior to the low-dose group and there were no differences between the two high-dose schedules. Once daily dosing, which is also a common dosing strategy for quetiapine, is also supported in the literature.
(160) The 
feasibility of such a dosing schedule, which does not seem to be predicted by peripheral pharmacokinetic parameters, is possible because quetiapine appears to interact centrally with both D2 and 5-HT2A receptors much longer than its 6 h elimination half-life.
(161)

(161)
Ziprasidone has a half-life of 4 to 10 h. Twice-daily administration is possible despite this relatively short half-life. Clinically, many patients are prescribed this medication only once daily. Regardless, ziprasidone should always be taken after eating in order to facilitate absorption. About two-thirds of ziprasidone is metabolized by aldehyde oxidase into inactive metabolites. The remainder is metabolized by CYP3A4 and CYP1A2 into inactive metabolites. At the current time, there are no known drug interactions with zipra-sidone at the level of aldehyde oxidase, since enzymatic activity does not appear to be altered by coadministered drugs. Although CYP3A4 appears to play only a minor role in the metabolism of ziprasidone, potent inhibitors or inducers of CYP3A4 may signiﬁ  -
cantly alter plasma concentrations of ziprasidone,
(162) and may

(162) and may 
thus necessitate an adjustment in dosage. The use of concomitant medications that may prolong the QTc interval should be avoided. Ziprasidone is contraindicated for patients with a history of known QT prolongation, recent acute myocardial infarction, or uncom-promised heart failure.
Aripiprazole is well absorbed from the gut, and has an elimination half-life of 75 hours. It is metabolized primarily by CYP3A4 and 2D6 isoenzymes into an active metabolite, dehydro-aripiprazole, which has a half-life of 94 hours. This pharmacokinetic pattern supports once daily dosing. Because aripiprazole is metabolized by CYP3A4 and 2D6, known inhibitors or inducers of these isoenzymes may result in increased or decreased clearance of aripiprazole and dehydro-aripiprazole.
(163)
(vi) Paliperidone, Iloperidone, and Amisulpride

(163)
Paliperidone is currently marketed in the US and abroad only in an osmotically controlled extended release formulation, which results in steady release of active drug over a 24 hr period. Hepatic metabolism is not considered a major route of clearance. Paliperidone is converted into metabolites that are not believed to contribute signiﬁ  cantly to its overall pharmacological activity. 
Few signiﬁ  cant drug-drug interactions at the level of the CYP450 
system are therefore anticipated. Even so, the plasma concentra-tion of paliperidone may be altered by drug interactions at CYP3A4.
(164)
Iloperidone has a half-life of 12 to 15 h. Its absorption is not 
affected by food. It should be titrated slowly because of orthostatic hypotension, and close monitoring is warranted when it is com-bined with antihypertensive drugs or drugs that are associated with orthostatic effects. The optimal dose has not yet been established

but is likely to be in the 5 to 10 mg/day range. Amisulpride has a half-life of 10 to 15 h. It is well tolerated. As yet, there are no known drug interactions. More information regarding the meta-bolic handling and potential for drug-drug interactions for both of these medications is anticipated as they continue to be further developed.
Typical neuroleptics
The adverse effects that are most routinely concerning for antipsy-chotic drug treatment are extrapyramidal adverse effects (EPS), especially for typical neuroleptic mediations. For typical neurolep-tics, high-potency drugs such as haloperidol and ﬂ  uphenazine 
are more likely to produce EPS than low-potency agents such as chlorpromazine and thioridazine. The latter may have lower potential for extrapyramidal side-effects than other typical neuroleptics because of its relatively higher afﬁ  nity for muscarinic

receptors. Atypical antipsychotic drugs are less likely to cause EPS during acute and long term tretment. There are a wide range of extrapyramidal side-effects produced by the typical neuroleptics, including dystonic reactions when ﬁ  rst administered, akathisia 
during the ﬁ  rst 2–3 weeks, parkinsonism during the ﬁ  rst several 
weeks with variable persistence, neuroleptic malignant syndrome at any time point but usually in the initial weeks, and tardive dyskinesia.
Dystonic reactions  due to neuroleptic drugs can be treated 
with parenteral anticholinergic agents or diphenhydramine, an antihistamine with some anticholinergic properties. The use of anticholinergic and other agents to manage parkinsonism due to typical neuroleptic drugs will be discussed subsequently.
Akathisia  may be the most common of the EPS effects, 
occurring in up to 70 per cent of patients treated long term with haloperidol.
(165) The term refers to a subjective uncomfortable

(165) The term refers to a subjective uncomfortable 
experience of motor restlessness which is relieved by movement. As such, patients will complain of discomfort, and manifest increases in psychomotor behaviour. These symptoms can be so distressing as to increase the risk of agitation or even suicidal behaviours.
(166)
Although patient age does not seem to inﬂ  uence risk of developing

(166)
Although patient age does not seem to inﬂ  uence risk of developing 
akathisia, women are believed to be at higher risk. Accurate diagno-sis of this condition is necessary in order to prevent inadvertent increases in neuroleptic dose from a belief that the patient’s discomfort from akathisia is due instead to worsening psychosis. This effect may be managed by reduction in dosage or switching medications to an atypical antipsychotic drug or a drug that is less likely to cause akathisia. When these strategies are not feasible, the symptoms may respond to anticholinergic medications, usually within 3–7 days. Other options include low doses of benzodiaze-pines or beta-adrenergic blockers, assuming no contraindications to either.
Parkinsonism  caused by antipsychotic drugs resembles idio-
pathic parkinsonism. Diagnostically, severe neuroleptic induced parkinsonism may resemble depression or negative symptoms

pathic parkinsonism. Diagnostically, severe neuroleptic induced parkinsonism may resemble depression or negative symptoms 
of schizophrenia; however, the associated motor signs and time course of symptoms in relation to starting antipsychotic treatment distinguish the former. Like akathisia, the onset and severity of antipsychotic induced parkinsonism is related to medication

1223
dosage; thus, a lowering of the dose or switching to a medication 
that is less likely to cause this effect may provide signiﬁ  cant relief, 
or ameliorate the parkinsonian signs and symptoms altogether. When this is not feasible, anticholinergic medications may provide relief, typically within 3–7 days. The response to anticholinergic medication is quite variable, however.
T ardive dyskinesia  emerges at various rates depending upon 
age, sex, and diagnosis.
(167, 168) The rate in younger patients is

(167, 168) The rate in younger patients is 
between 3 and 5 per cent per year. It is higher in bipolar than schizophrenic patients and much higher in people above the age of 60. It is related to dose and will be less likely with lower doses of typical neuroleptics. Tardive dyskinesia is ordinarily reversible, although irreversible and/or extremely severe and rarely life-threat-ening forms can occur. The best way to minimize its occurrence is to use an atypical antipsychotic drug in lieu of a typical agent, since these drugs as a class are associated with a much lower risk of tardive dyskinesia.
(167) Patients with mood disorders should gener-
ally not receive maintenance treatment with typical antipsychotic drugs unless mood stabilizers alone prove insufﬁ  cient because 
they are at greater risk for tardive dyskinesia. There are no deﬁ  ni-

tive treatments for tardive dyskinesia. Generally, the best strategy is prevention through the use of atypical antipsychotic drugs, and periodic screening with a structured assessment tool such as the Abnormal Involuntary Movement Scale (AIMS). There is some suggestion in the literature that continuation of antipsychotic treatment does not worsen tardive dyskinesia, and may eventually result in a stabilization and improvement of tardive symptoms. Switching to clozapine appears to be helpful, although such an effect is not invariable.
Neuroleptic malignant syndrome  is a rare life-threatening side-
effect related to an apparent compromise of the neuromuscular 
and sympathetic nervous systems.
(169) It usually occurs at the ini-

tiation of treatment with a high-potency agent but may occur with any of the typical (or atypical agents) at any point. Immediate discontinuation of the medication is essential. The condition is characterized by muscle rigidity, breakdown of muscle ﬁ  bres lead-

ing to large increases in plasma creatine kinase activity, fever, autonomic instability, changing levels of consciousness, and some-times death. It may be treated by discontinuing all antipsychotic drug treatment, applying external hypothermia, supporting blood pressure, and administering a direct-acting dopamine agonist such as bromocriptine or pergolide, and dantrolene sodium, which  blocks the release of intracellular stored calcium ions. After its successful treatment, an atypical antipsychotic should be used even though these agents, including clozapine, may also induce 
neuroleptic malignant syndrome.
The typical neuroleptic drugs produce a wide variety of 
other side-effects , including weight gain, seizures (especially

other side-effects , including weight gain, seizures (especially 
pimozide), sedation, hypotension, elevated liver enzymes, retinitis pigmentosa (thioridazine), orthostatic hypotension, prolongation of the QTc interval (low potency phenothiazines, pimozide) and anticholinergic effects (mesoridazine, chlorpromazine, thioridazine). All the typical neuroleptic drugs produce marked increases in serum prolactin levels, with the increases being greater in females than males.
(25) Prolactin elevations may 
affect sexual function in both males and females, with difﬁ  culty 
achieving erection or orgasm among the most common side-effects.
(25)Atypical antipsychotic drugs
(a) Clozapine
(i) Agranulocytosis
It has now been reliably established that clozapine produces agranulocytosis in slightly less than 1 per 100 patients.
(170, 171)

(170, 171)
This is 15 to 30 times the rate associated with the phenothi-azines and possibly higher than that for the butyrophenones. The peak of agranulocytosis with clozapine occurs between 4 and 18 weeks, and then falls off sharply. Weekly monitoring of the white cell or absolute neutrophil count is required for 26 weeks in most countries, with the frequency decreasing to biweekly or monthly thereafter, sometimes on a voluntary basis. In the US, monthly monitoring is required assuming no hematological abnormalities after one year of treatment. The cost-effectiveness of monitoring after a year has not been studied but it is probably in the range that would lead to its abandonment by current standards. With monitoring, agranulocy-tosis can usually be detected before infection sets in or becomes overwhelming. Discontinuation of clozapine, beginning treatment

with colony cell stimulating factors, and the usual procedures 
for treating an infection are usually effective in restoring the white cell line.
(ii) Other side-effects
Clozapine produces a wide range of side-effects.(171) These can 
generally be managed by dose adjustment and concomitant medications. Clozapine produces hypotension because of its potent α
1-adrenoceptor antagonism and must be slowly titrated in most 
patients. Low-dose glucocorticoid treatment may be helpful in some patients with severe hypotension. Clozapine rarely if ever produces signiﬁ  cant extrapyramidal side-effects, although some 
cases of akathisia and neuroleptic malignant syndrome have been reported.
Major motor seizures are another important side-effect of

Major motor seizures are another important side-effect of 
clozapine. They are dose related, with the incidence being about 2 per cent in patients at low doses and 6 per cent at doses greater than 600 mg/day. They are sometimes preceded by myoclonic jerks. Valproic acid and dose reductions are usually effective in preventing the progression of myoclonic jerks or treating major motor seizures. Other anticonvulsants can be combined with clozapine if needed, though caution would be clearly warranted 
with the use of carbamazepine due to its potential for bone marrow 
suppression.
Hypersalivation is another side-effect. It usually responds to anti-
cholinergic therapy or to clonidine. Exacerbation of obsessive-com-pulsive symptoms has been reported with clozapine. Augmentation with an SSRI or lithium carbonate is usually effective.
Weight gain is a frequent side-effect of clozapine, with about

Weight gain is a frequent side-effect of clozapine, with about 
30 per cent of patients gaining more than 7 per cent of body weight.
(171) Diet and exercise are useful in minimizing this effect. 
A related problem is the emergence of insulin resistance or type II diabetes, or exacerbation of existing diabetes, with or without atherogenic changes in serum lipid proﬁ  le. There have also been 
reports of diabetic ketoacidosis that emerged in the context of clozapine treatment. Of the atypical antipsychotic drugs, clozapine and olanzapine are associated with the highest risk for clinically signiﬁ  cant weight gain, as well as abnormalities in glycaemic con-
trol and lipid homeostasis.
(123)6.2.5 antipsychotic and anticholinergic drugs

SECTION 6  treatment methods in psychiatry 1224
Somnolence, tachycardia, hypertension, constipation and 
stuttering are also produced by clozapine. Tachycardia is treated only when the pulse is greater than 100 beats/minute. β-Blockers 
are effective to reduce the heart rate, but may also result in syner-gism of hypotensive effects.
(171)
There have been reports of clozapine-associated myocarditis and 
cardiomyopathy.(172)The presence of eosinophilia accompanied by 
cardiotoxic signs such as tachycardia, fatigue, orthostasis, or respi-ratory problems (many of which are adverse effects of clozapine) should alert the clinician to the possibility of myocarditis and the need for medical evaluation.
Finally, treatment with clozapine may not uncommonly result in

Finally, treatment with clozapine may not uncommonly result in 
an asymptomatic mild elevation in hepatic transaminase levels; however, there have also been reports of hepatotoxicity in the setting of clozapine treatment. Polypharmacy appears to be a risk factor. Cases of fulminant hepatotoxicity leading to liver failure are rare.
(iii) Risperidone
Risperidone is associated with moderate weight gain, comparable to that of typical neuroleptic drugs in most cases, and less than that of clozapine and olanzapine.
(123,173)  Risperidone also produc-
es some postural hypotension because of its α1-adrenoceptor 
blocking properties. Risperidone produces greater increases in serum prolactin secretion than any of the other atypical antipsy-chotic drugs.
(25) The increases appear to be at least comparable 
to those of typical neuroleptics.(173) At higher doses, particu-
larly above 6 mg daily in most adults, the incidence of EPS also increases,

(77) though typically not to the degree observed when 
using typical neuroleptic drugs in clinical practice. Risperidone, like clozapine and other agents of this type, can sometimes exacer-bate or induce symptoms of obsessive-compulsive disorder and tics, probably due to its antiserotonergic properties. This can be counteracted in some patients by the addition of an SSRI. Risperidone is not associated with agranulocytosis or increased risk of seizures. Because of its low afﬁ  nity for muscarinic receptors, 
risperidone treatment is not associated with signiﬁ  cant anticholin-
ergic effects.
(iv) Olanzapine

Olanzapine also produces dose-dependent extrapyramidal side-effects, including some dystonic reactions in patients with schizophrenia, but these are less frequent and severe than those produced by typical neuroleptic drugs or risperidone.
(173)
Olanzapine is less well tolerated than clozapine in patients with Parkinson’s disease. Olanzapine, like other atypical antipsychotic drugs, is associated with a lower risk of tardive dyskinesia than typical neuroleptics.
The major side-effect of olanzapine is weight gain.
(173) Large 
weight gains due to increased appetite occur in 10 to 15 per cent of olanzapine-treated patients during the ﬁ  rst 6 months of treatment.

weight gains due to increased appetite occur in 10 to 15 per cent of olanzapine-treated patients during the ﬁ  rst 6 months of treatment. 
Another 20 to 35 per cent gain between 7 and 10 per cent of body weight. These gains tend to become permanent for as long as patients continue the medication. Like clozapine, olanzapine is also associated with higher risk of insulin resistance, glycaemic changes, and development of atherogenic changes in lipid proﬁ  le.
(123) Cases 
of diabetic ketoacidosis associated with olanzapine treatment have been reported.
Olanzapine is also associated with some increase in liver enzymes, 
orthostatic hypotension, anticholinergic side-effects, and sedation. Many of these adverse effects are time limited and reduce in inten-
sity or resolve over the ﬁ  rst few weeks of treatment with continu-

ous use. Olanzapine produces transient increases in serum prolactin levels, which are smaller in magnitude than those produced by typ-ical neuroleptic drugs or risperidone.
(25, 173)
Olanzapine, like other agents of this type, can occasionally exac-
erbate or induce symptoms of obsessive-compulsive disorder and tics, probably due to its antiserotonergic properties. This can be counteracted in some patients by the addition of an SSRI. Olanzapine is not associated with agranulocytosis or increased risk of seizures.
(v) Quetiapine
Quetiapine appears to have fewer extrapyramidal side-effects than either risperidone or olanzapine.
(158, 173) Quetiapine is tolerated

(158, 173) Quetiapine is tolerated 
in patients with Parkinson’s disease to a much greater extent than risperidone or olanzapine. The incidence of extrapyramidal side-effects with quetiapine in schizophrenic patients appears to be comparable to placebo. The major side-effects with quetiapine are headache, agitation, dry mouth, dizziness, weight gain, and postural hypotension.
(173)
With regard to weight gain and other metabolic effects, quetiap-
ine treatment appears to confer moderate risk—similar to that of risperidone, but less than that associated with clozapine or olan-zapine treatment.
(123) Far less is known about the long term effects 
of quetiapine on markers of glycaemic and lipid homeostasis. Nevertheless, clinically signiﬁ  cant changes in serum lipids have 
been reported.
Decreased serum thyroid hormone levels, increased hepatic

Decreased serum thyroid hormone levels, increased hepatic 
transaminases and elevated serum lipids have been reported. Decreases in total and free thyroxine, when they occur, are mild, non-progressive, and are not believed to be clinically signﬁ  ciant. 
The effect may be dose dependent. Similar to clozapine, asymp-tomatic elevations in hepatic transaminases may be encountered early in the course of treatment, followed by a return to baseline values. Animal studies suggest an increased risk of cataracts.
(173)
Periodic ophthalmological screening for lenticular opacities is recommended by the manufacturer, though no causal relationship between the use of quetiapine and the development of cataracts has been demonstrated to date.
(vi) Ziprasidone

Ziprasidone does not increase serum prolactin levels and is virtu-ally devoid of extrapyramidal side-effects, weight gain, and changes in markers of glucose handling and lipid metabolism. Its major side-effects are nasal congestion and somnolence,
(173) the latter of 
which is usually transient. There has been some concern of cardio-vascular side-effects, for example increased QTc interval; however, perusal of the available data does not reveal a signiﬁ  cant problem 
in this regard. However, caution is warranted when considering the coadministration of ziprasidone with other drugs that are known to prolong the QTc interval, since ziprasidone has been associated with a signiﬁ  cant increase in the QTc interval of 16.6 msec, which 
was greater than that of other atypical antipsychotics and haloperi-dol, but less than thioridazine.
(174) Screening for electrolyte

(174) Screening for electrolyte 
abnormalities and cardiac disease (including recent myocardial infarction, congestive heart failure symptoms and arrythmias with or without syncope) may be indicated prior to starting ziprasidone.

1225
(vii) Aripiprazole and paliperidone
Aripiprazole is well tolerated, and does not appear to routinely 
cause EPS or hyperprolactinaemic changes at recommended dos-ages. This also appears to be the case for higher than recommended doses. Aripiprazole is also not associated with clinically signiﬁ  cant 
increases in weight, or changes in markers of glucose handling or lipid homeostasis. Both aripiprazole and ziprasidone are therefore believed to be the atypical antipsychotic drugs with the most advantageous metabolic risk proﬁ  le.
Paliperidone in its extended release form also appears to be well

Paliperidone in its extended release form also appears to be well 
tolerated during short term, acute phase treatment. In these stud-ies, the most common side effect was tachycardia. Rates of discon-tinuation due to adverse effect burden were also very low. The risk of hyperprolactinaemic changes with paliperidone appears to resemble those of risperidone, although no head-to-head compari-sons have been carried out. The changes in prolactin levels may be dose related. The EPS burden associated with paliperidone during the short term studies was low for the 6 mg dose; however, at higher doses, the incidence of EPS appears to be higher. Measures of weight and metabolic effects during 6 week treatment with paliperidone showed no significant changes from baseline. Similar results were found for paliperidone during medium-term treatment.
(141)
Future long term studies will add greatly to our understanding of paliperidone’s adverse effect proﬁ  le.

(141)
The main indication for the antipsychotic drugs is the treatment of 
all phases of schizophrenia, including acute, ﬂ  orid symptoms of 
psychosis, prevention of relapse, and deﬁ  cit symptoms. Important

psychosis, prevention of relapse, and deﬁ  cit symptoms. Important 
other uses include the psychotic phase and prophylaxis of mania, depression with psychotic features, the psychosis, agitation, and aggression of various dementias, the treatment of psychoses due to l-dopa or other dopamine agonists in Parkinson’s disease, T ourette’s syndrome, treatment-resistant obsessive-compulsive disorder, self-injurious behaviour, porphyria, antiemesis, intractable hiccoughs, and as antipruritics. Some current research has suggested that the antipsychotic drugs may be of use to prevent the onset of schizo-phrenia by administering them to individuals who are in the pro-dromal phase of the illness. The atypical antipsychotics may be effective for augmenting antidepressants in patients with treat-
ment-resistant non-psychotic depression, and are being tried on an

ment-resistant non-psychotic depression, and are being tried on an 
experimental basis for various character disorders such as border-line, schizoid, and schizotypal personality disorders. Clozapine, which has the lowest incidence of extrapyramidal side-effects of any of the antipsychotic drugs, has some special applications in neurological conditions such as essential tremor and the treatment of the water intoxication syndrome in schizophrenic patients. The uses of the classical antipsychotics such as chlorpromazine and haloperidol have been limited by their side-effects, especially parkinsonism and tardive dyskinesia, a slowly developing, some-times irreversible series of abnormal involuntary movements involving facial, limb, and girdle muscles. As has been discussed, the atypical antipsychotic drugs such as clozapine, olanzapine, que-tiapine, and risperidone, as well as iloperidone and ziprasidone, which are in development, have signiﬁ  cant advantages with regard

to parkinsonism. Clozapine deﬁ  nitely has a vastly reduced risk of 
tardive dyskinesia and the other atypical agents most likely have a risk that is less than that of the typical neuroleptic drugs but more than clozapine. Uses in other psychiatric and neurological condi-
tions may be expected to emerge as the safety proﬁ  le of these agents 
is better described.
Antiparkinsonian agents
Anticholinergic drugs
Antiparkinsonian medications, including anticholinergic, antihis-taminic, benzodiazepines, dopamine agonists, and β-blockers are 
of importance in the management of extrapyramidal side-effects. They are usually needed with the typical neuroleptic drugs but some patients will require antiparkinsonian treatment with olan-zapine, risperidone, or quetiapine. The anticholinergics and the antihistaminics (e.g. diphenhydramine) are used to treat acute dys-kinesias and dystonias, pseduoparkinsonian symptoms (tremor, rigidity, bradykinesia, shufﬂ  ing gait), and akathisia. These agents

act centrally in the basal ganglia to block the effects of increased acetylcholine release due to D
2-receptor blockade. The most widely 
used anticholinergic drugs are benztropine, biperiden, procycli-dine, and trihexyphenidyl. Benztropine is given in doses of 1 to 6mg/day usually in divided doses. Biperiden is given in doses of 2 to 16 mg/day in two or three doses. Procyclidine is given in divided doses of 5 to 30 mg/day. Trihexylphenidyl is given in doses of 1 to 15 mg/day, in a single or divided dose.
These agents are competitive antagonists of the ﬁ  ve subtypes of 
muscarinic receptors that have been identiﬁ  ed and which are 
labelled M
1 to M5. They have minimal antagonist effect at nicotinic 
cholinergic receptors. Blockade of cholinergic receptors on intra-striatal neurones by these agents restores the cholinergic balance, which is disrupted by blockade of D
2 dopamine receptors by some

2 dopamine receptors by some 
antipsychotic agents. Other central effects include impairment of various forms of memory. Elderly patients in particular may develop anticholinergic-induced agitation, irritability, disorientation, hal-lucinations and delirium because of the natural loss of cholinergic neurones with aging.

These agents have some preference for the central nervous system but some peripheral anticholinergic effects are to be expected. Blockade of vagal tone in the heart produces tachycardia. Other adverse effects include decreased bladder function and urinary retention and decreased bowel motility leading to constipation and impaction. Decreased saliva and bronchial secretion contribute to dry mouth and increased dental caries while decreased sweating increases the risk of heat stroke. Blockade of muscarinic receptors in the eye cause pupillary dilation and inhibition of accommoda-tion, leading to photophobia and blurred vision. Rarely, narrow-angle glaucoma may ensue. The muscarinic receptors in the basal ganglia are predominantly M
2 whereas those in the periphery 
are M1. The rank order of the anticholinergic drugs for relative 
selectivity for the M2 receptor is biperiden, procyclidine, trihexyl-

phenidyl, and benztropine. All these agents can cause dry mouth, blurred vision, urinary retention, constipation, and increased intra-ocular pressure. They may cause anticholinergic delirium in elderly patients or after taking high doses. Biperiden is less likely to cause peripheral anticholinergic effects. Benztropine, biperiden, and tri-hexyphenidyl may cause euphoria because of their ability to inhib-it dopamine reuptake and may be subject to abuse.6.2.5 antipsychotic and anticholinergic drugs

SECTION 6  treatment methods in psychiatry 1226
The anticholinergic drugs or the antihistamine diphenhydramine 
are given intramuscularly for the treatment of acute dystonic reactions. They are usually effective within minutes and may have to be repeated. It is usually not necessary to prescibe an oral anti-cholinergic following a dystonic reaction, though some may require their brief use depending on which anipsychotic is prescribed. These agenst should not be given prophylactically unless the patient is at established risk for EPS at the dose of antipsychotic which is being started. If akathisia or parkinsonism develops following treatment with a typical neuroleptic drug, the ﬁ  rst consideration 
should be whether to continue to use the offending agent and drop the dosage or to substitute an atypical antipsychotic drug. If decreasing the dose of antipsychotic drugs does not sufﬁ  ce or is

should be whether to continue to use the offending agent and drop the dosage or to substitute an atypical antipsychotic drug. If decreasing the dose of antipsychotic drugs does not sufﬁ  ce or is 
not clinically feasible, substituting an atypical agent is the clearly the recommended choice since it avoids all the unpleasant side-effects of the anticholinergic agents. 
Other drugs
Amantadine, which also has antiviral actions, is able to increase the release of dopamine in the basal ganglia, which diminishes the release of acetylcholine. It may improve acute dystonias, akathisia, akinesia, parkinsonism, and tardive dyskinesia. It has also been reported to improve sexual function and decrease weight gain due to neuroleptic drugs. It may cause increased arousal, agitation, and indigestion, however. The usual oral dose is 100 to 400 mg/day.
β-Blockers such as propranolol, atenolol, and pindolol are

β-Blockers such as propranolol, atenolol, and pindolol are 
useful for treating akathisia and tremor. They may cause bradycar-dia, and particularly immediate-release forms should not be stopped abruptly due to rebound tachycardia.
Benzodiazepines, such as clonazepam, lorazepam, and diazepam, 
are useful for treating akathisia, acute dystonias, and acute dyskine-sias. They can cause drowsiness and lethargy, and have abuse 
potential.
Antipsychotic drugs are invaluable tools in treating a large variety 
of patients with schizophrenia and other conditions. Their main beneﬁ  ts are, in fact, to treat psychotic symptoms, but the newer

of patients with schizophrenia and other conditions. Their main beneﬁ  ts are, in fact, to treat psychotic symptoms, but the newer 
agents in particular may improve negative symptoms, cognition, mood, anxiety, and aggression as well. The evidence for atypical antipsychotic drugs to improve cognition is steadily increasing and this should be one of the driving forces behind the substitution of these agents for the typical antipsychotic drugs. Recent evidence of volumetric increases in cerebral cortical gray matter associated with atypical, but not typical, antipsychotic drugs may be related to improvement in such symptoms.
(175) As such, atypical antipsy-
chotic drugs may produce ‘disease modifying’ rather than just ‘symptomatic’ effects, a matter that is of considerable current interest.
Antipsychotic drugs are useful as both acute and maintenance

Antipsychotic drugs are useful as both acute and maintenance 
treatments to prevent the recurrence of psychotic symptoms. The extrapyramidal side-effects and greater tardive dyskinesia risk of the typical antipsychotics, coupled with their lesser efﬁ  cacy to 
improve negative symptoms and cognition suggest that newer agents are preferred. Clozapine, despite its risk of agranulocytosis, is the treatment of choice for patients who fail to respond to other typical or atypical antipsychotic agents. Risperidone, olanzapine, 
quetiapine, ziprasidone, aripiprazole and paliperidone have some-what different pharmacologic proﬁ  les. It is not clear which of these 
agents should be tried in a given patient but on going research may clarify that. These agents, and clozapine, appear to differ signiﬁ  -

cantly in their propensity for causing clinically signiﬁ  cant changes

in weight and markers of metabolic status. Amisulpride has a mechanism of action different from that of the other atypical agents, with some preference for treating negative symptoms. These compounds, as well as others expected to be approved for use in the near future, for example iloperidone and asenapine, will need to be compared with each other to determine if differential indica-tions exist. Side-effect differences among these drugs as well as the availability of long-acting preparations may help clinicians choose among them. Cost-effective analyses currently favour use of the atypical antipsychotic drugs because of better compliance leading to less frequent relapses and shorter hospital stays. They also facili-tate retention of work skills and return to work which decreases the indirect costs of illness in patients still young enough to be able to work. As long as the typical antipsychotics remain in use, and for some patients who receive atypical agents, anticholinergic and

costs of illness in patients still young enough to be able to work. As long as the typical antipsychotics remain in use, and for some patients who receive atypical agents, anticholinergic and other antiparkinsonian drugs will continue to be necessary to treat extrapyramidal side-effects.

Because of the compliance problem, which is less with the atypi-
cal than the typical antipsychotics, it is important to develop more long acting atypical drugs. Risperidone is currently available in such a form, and paliperidone and olanzapine will also be in the near future. While the current group of atypical antipsychotic drugs is predominantly characterized by relatively more potent 5-HT
2A than D2 receptor antagonism, it is likely that a number of 
different strategies will emerge for compounds which produce fewer extrapyramidal side-effects than the typical neuroleptics. Because these compounds are so effective in that regard, the real challenge is to develop agents which address other key features of schizophrenia, especially cognitive impairment and negative symp-toms, without the side-effect burden of this group of compounds.
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of Clinical Psychiatry ,68, 826–31.6.2.6 Antiepileptic drugs
Several drugs originally developed to treat epilepsy have been

Several drugs originally developed to treat epilepsy have been 
found effective in certain psychiatric disorders. This chapter reviews the antiepileptic drugs most extensively studied in psychiatric disorders: valproate, carbamazepine, lamotrigine, and topiramate. We then brieﬂ  y mention six other antiepileptics currently under 
investigation in various psychiatric disorders, but not yet exten-sively studied: gabapentin, oxcarbazepine, levetiracetam, tiagabine, zonisamide, and pregabalin. The antiepileptic drug phenytoin is rarely used in psychiatric disorders, and is therefore not included in this chapter. The benzodiazepines, which have antiepileptic prop-erties, are also omitted here, as they are discussed in Chapter 6.2.2. We brieﬂ  y list studies documenting the efﬁ  cacy of these various agents

in psychiatric disorders, but the reader is referred to the individual chapters on speciﬁ  c disorders for a more detailed discussion of 
treatment strategies.
Valproate1
Valproate (valproic acid) is a simple branched-chain carboxylic 
acid, first used as an organic solvent in the late 1800s (see Fig. 6.2.6.1). Its antiepileptic properties were discovered serendipi-tously in 1963, and its clinical use as an antiepileptic drug began in 1964. As early as 1966, valpromide (the amide precursor of valproate) was reported to be effective in the treatment of bipolar disorder.
(1) Since then, valproate has been used effectively in the 
treatment of numerous psychiatric and neurologic conditions, and is now widely used as a mood stabilizer in the treatment of bipolar disorder.
Valproate is currently available as ﬁ  ve different preparations:

Valproate is currently available as ﬁ  ve different preparations: 
valproate (Depakene), sodium valproate (Depakene syrup), dival-proex sodium (Depakote) (which is an equal proportion of sodium valproate and valproic acid), divalproex sodium sprinkle capsules (Depakote sprinkle capsules), and valpromide (the amide precur-sor of valproate, which is available in Europe, but not in the United States).
The mechanism of action of valproate in the treatment of epilepsy is unclear, but appears to be related to increased levels of gamma-aminobutyric acid (GABA) in the brain. It inhibits the breakdown and turnover of GABA, increases its release, and increases the density of the GABA- ββ receptor subtype.
(2)
Its mechanism of action in treating psychiatric disorders is 
unknown.6.2.6 antiepileptic drugs
1Valproate is marketed in the British Commonwealth as ‘valproic acid’ and

(2)
1Valproate is marketed in the British Commonwealth as ‘valproic acid’ and 
as ‘sodium valproate’ in the US, but these are effectively interchangeable as they both yield valproate in the bloodstream.

SECTION 6  treatment methods in psychiatry 1232
All preparations of valproate are completely absorbed after oral 
administration. The rate of absorption varies slightly with the dif-
ferent preparations, but these differences are probably not clinically 
signiﬁ  cant. Co-administration with food can delay absorption. 
Valproate is approximately 90 per cent protein-bound. Only the 
unbound drug crosses the blood brain barrier and is pharmaco-
logically active in the CNS. As total serum valproate concentration 
increases, the unbound portion of valproate is disproportionately 
increased, presumably due to saturation of the protein-binding 
sites. Therefore, at higher serum concentrations, small increases in 
dose may result in signiﬁ  cant changes in efﬁ  cacy and side effects. 
Valproate is metabolized by the liver to a glucuronide conjugate or 
one of several metabolites, some having anti epileptic activity. The

one of several metabolites, some having anti epileptic activity. The 
half-life of valproate ranges from 6 to 17 h. Enzyme-inducing 
antiepileptic drugs, such as carbamazepine and phenytoin, shorten 
the half-life of valproate (see Interactions).(3)
Valproate is often associated with minor side effects, but can rarely 
cause life-threatening, idiosyncratic reactions. Common side effects 
include gastrointestinal symptoms, such as nausea, vomiting, 
abdominal pain, and diarrhoea; and neurological symptoms, 
such as tremor, somnolence, and dizziness. Weight gain is also 
common. Hair loss occurs in some patients, but is often transient 
and reversible upon discontinuation of the drug. Rare, but poten-
tially fatal, idiosyncratic reactions include hepatic failure, acute 
haemorrhagic pancreatitis, and agranulocytosis.(2,4) Known risk 
factors for irreversible hepatic failure include young age (especially

factors for irreversible hepatic failure include young age (especially 
less than 2 years old), developmental delay, a metabolic disorder, 
or concomitant administration of other antiepileptic drugs.(5)Because of this risk, liver function tests are recommended prior 
to initiation of therapy and periodically thereafter (see Dosage and 
Administration).
(a) Overdose
Overdose with valproate can result in heart block, coma, and death. 
Haemodialysis may be useful in clearing the drug rapidly, and 
naloxone may reverse the CNS depressant effects.(3)
(b) Pregnancy
Valproate increases the risk of neural tube defects (such as spina 
biﬁ da) to approximately 1–2 per cent of pregnancies when admin-
istered in the ﬁ  rst trimester. Other reported congenital anomalies 
include craniofacial defects and cardiovascular malformations. 
Valproate is found in human breast milk, at approximately 1–10

Valproate is found in human breast milk, at approximately 1–10 
per cent of serum concentrations, but its effects on the nursing 
child are unknown.(6)
Controlled trials conﬁ  rm that valproate is effective in the treatment 
of multiple seizure types, including complex partial, simple and 
complex absence, generalized tonic–clonic, and myoclonic seizures.(3)
Several controlled studies indicate efﬁ  cacy in the treatment of 
acute mania,(7–13) mixed episodes,(12,14) and in the prophylaxis of 
recurrent mood episodes.(13,15,16) One small controlled study has 
offered limited evidence for the efﬁ  cacy of valproate in the treat-
ment of bipolar depression.(17) There is growing support from 
controlled studies for the efﬁ  cacy of valproate, combined with 
both typical and atypical antipsychotics, in the treatment of acute

both typical and atypical antipsychotics, in the treatment of acute 
exacerbations of schizophrenia(18,19); particularly when the presen-
tation includes agitation and hostility.(20) There are also several 
small controlled studies demonstrating the beneﬁ  t of valproate in 
the treatment of mood instability and impulsivity associated 
with borderline personality disorder.(21–23) Other conditions for 
which valproate may sometimes be useful include pain syndromes, 
anxiety disorders, alcohol and sedative withdrawal syndrome, 
impulse control disorders, and behavioural and affective distur-
bances associated with intellectual disability and dementia.(2)
Valproate is contraindicated in patients with known hypersensi-
tivity to the drug. It should be used cautiously in patients with 
signiﬁ  cant hepatic disease.

In general, valproate can be combined safely with other psychotropic 
medications and antiepileptic drugs. However, given that valproate is 
highly protein-bound and can inhibit hepatic enzymes, some drug–
drug interactions have been identiﬁ  ed.(3)Aspirin , which is highly 
protein-bound, elevates the free fraction of valproate, resulting in 
increased effects of valproate on the CNS. Valproate can displace 
diazepam ,phenytoin ,carbamazepine , and warfarin  from protein-
binding sites, resulting in increased activity of these drugs. Co-
administration of valproate with lamotrigine  signiﬁ  cantly increases 
the half-life of the latter and can increase the risk of lamotrigine-
induced rashes. When administered with carbamazepine , three 
potential interactions may occur: (1) valproate can increase the con-

centration of carbamazepine’s metabolite, carbamazepine-10,11-
epoxide, by inhibiting its further metabolism; (2) carbamazepine 
may lower the valproate level; and (3) valproate may increase the 
carbamazepine level.(24) Therefore, close monitoring of serum 
Topiramate
(e)
Fig. 6.2.6.1 Molecular structures of selected antiepileptic drugs. (a) Valproate, 
(b) Carbamazepine, (c) Oxcarbazepine, (d) Lamotrigine, and (e) Topiramate.

1233
concentrations of both drugs is important when they are combined. 
Amitriptyline  and ﬂ uoxetine  may increase serum valproate concen-
trations, possibly by inhibition of valproate metabolism.
As with other antiepileptic drugs, valproate should be tapered grad-ually over several weeks to minimize the risk of rebound seizures.
Dosage and administration
Before initiating treatment with valproate, it is advisable to obtain a baseline complete blood count (CBC), liver function tests (LFTs), and if appropriate, a pregnancy test. CBC and liver function tests should be performed monthly for the ﬁ  rst 3 months, and, if no

abnormalities are found, every 6 to 12 months thereafter. If hepatic transaminase levels increase to more than three times normal, valproate should be discontinued. If the transaminase levels even-tually return to baseline and the patient responded to valproate previously, re-challenge can be considered. If hepatic transaminase levels increase, but are less than three times normal, monitoring should be increased to once every 1–2 weeks until transaminase levels stabilize, and then monthly thereafter.
(2)
The initial starting dose of valproate in adults is 250 to 1000 mg 
per day, given in two or three divided doses (see Table 6.2.6.1 for dosage forms). The dose may be increased every 1–3 days depending on the patient’s response and tolerance. The usual therapeutic concentration is between 50–100 μg/ml (drawn 12 h

after the last dose) for both psychiatric and neurological disorders. Some clinicians give the entire daily dose of valproate at bedtime. In patients with seizure disorders or acute mania, an oral loading strategy can be used.
(25) In this situation, the patient receives 
20 mg/kg as a bolus on the ﬁ  rst day, resulting in rapid achievement 
of therapeutic levels. However, psychiatric patients who are not 
acutely manic usually have difﬁ  culty tolerating the oral loading 
strategy.
Carbamazepine (T egretol®) is an iminostilbene derivative with a structure similar to the tricyclic antidepressant imipramine (see Fig. 6.2.6.1). It was initially developed as a potential antidepressant 
in the 1950s, but was found to have antiepileptic and analgesic

in the 1950s, but was found to have antiepileptic and analgesic 
properties, and has been marketed for the treatment of seizures and pain syndromes since 1963. For many clinicians, it has been the preferred treatment for partial and generalized tonic–clonic seizures, as well as neuropathic pain. Its clinical use in affective 
disorders began in the early 1970s; since then, it has become widely 
used in psychiatry.
Carbamazepine’s mechanism of action in the treatment of seizures and pain syndromes is controversial, but probably results from blockade of voltage-sensitive sodium channels or enhancement 
of gamma-aminobutyric acid (GABA) activity. Its mechanism of action in psychiatric disorders is unknown, and may be different, 
given that it affects numerous neurotransmitter systems.
(26, 27)
Carbamazepine is absorbed slowly, with peak plasma levels

(26, 27)
Carbamazepine is absorbed slowly, with peak plasma levels 
occurring 4–5 h after administration of the tablets. Absorption is faster for the carbamazepine liquid, and slower for carbamazepine 
extended-release tablets. Oral bioavailability is about 80 per cent; plasma protein binding is approximately 75 per cent. 
The half-life of carbamazepine is variable, as it induces its own metabolism with chronic administration (autoinduction). Initially, the half-life ranges from 18–65 h, but after autoinduction is 
complete (usually 3–5 weeks), it is decreased to 5–25 h. Children metabolize carbamazepine more rapidly than adults, and therefore 
require higher doses to achieve similar levels. Carbamazepine is metabolized in the liver by the cytochrome P
450 system to a 
wide variety of metabolites, some with antiepileptic activity. The

wide variety of metabolites, some with antiepileptic activity. The 
predominant metabolite, carbamazepine-10, 11-epoxide (CBZ-E), is further metabolized by epoxide hydrolase to an inactive form. 
Most of carbamazepine’s metabolites are excreted as glucuronide conjugates in the urine.
(28, 29)
Carbamazepine is generally well tolerated, with less than 5 per cent of patients discontinuing the medication because of adverse effects. Common side effects seen during initiation of treatment 
include dizziness, ataxia, sedation, nausea, and diplopia. These 
are often mild in severity, and frequently resolve with continued treatment.
(a) Haematological side effects
Carbamazepine commonly causes a benign suppression of white 
blood cell count, but in rare cases may cause severe and potentially

blood cell count, but in rare cases may cause severe and potentially 
fatal blood dyscrasias, including agranulocytosis, pancytopenia, 
and aplastic anaemia. The incidence of these non-dose-related, idiosyncratic reactions has been estimated to range between 1 in 10 000 to 1 in 300 000.
(4)
(b) Hepatic toxicity
Carbamazepine is frequently associated with benign transaminase elevations. Very rarely, a non-dose-related, idiosyncratic reaction causes hepatic failure, which can be fatal.Table 6.2.6.1  Available dosage forms of antiepileptic drugs
Drug (proprietary name) Preparation
Valproate
 Valproate (Depakene)
 Valproate syrup (Depakene syrup)
 Divalproex sodium (Depakote)
 Divalproex sodium extended release (Depakote ER)
 Divlaproex sodium sprinkle capsules250 mg capsule
250 mg/5 ml
125, 250, and 500 mg tablets
250, 500 mg tablets
125 mg capsule
 Carbamazepine (Tegretol

Divlaproex sodium sprinkle capsules250 mg capsule
250 mg/5 ml
®)100, 200 mg tablets; 100 mg 
chewable tablets; suspension of 
100 mg/5 ml
 Carbamazepine extended-release tablets
  (Tegretol XR ®)
  ( C a r b a t r o l ®)
  (Equetro ®)100, 200, and 400 mg tablets
100, 200, and 300 mg capsules
Oxcarbazepine (Trileptal ®) 150, 300 and 600 mg tablets; 
suspension of 300 mg/5 ml
Lamotrigine (Lamictal ®) 25, 100, 150, and 200 mg tablets; 
2, 5, and 25 mg chewable tablets6.2.6 antiepileptic drugs

SECTION 6  treatment methods in psychiatry 1234
(c) Cardiovascular effects
Carbamazepine slows intracardiac conduction, and is relatively 
contraindicated in patients with heart block.
(d) Dermatologic effects
Rashes occur in 5–15 per cent of patients. These are usually benign, but rarely lead to exfoliative dermatitis, Stevens–Johnson syndrome, or toxic epidermal necrolysis. Therefore, it is usually recommended that the drug be discontinued if any rash develops.
(e) Endocrine effects
Carbamazepine can exert antidiuretic effects, which result in hyponatremia in 5–40 per cent of patients.
(30) Usually, this effect is 
clinically insigniﬁ  cant.
Carbamazepine can result in decrease in free T3 and T4, but clinical 
hypothyroidism is extremely rare.
Carbamazepine overdose can be fatal. Common symptoms include nystagmus, tremor, ophthalmoplegia, and myoclonus. Life-threatening effects include atrioventricular block, coma, seizures, and respiratory depression.
(31)

(31)
Carbamazepine exposure in the ﬁ  rst trimester results in neural 
tube defects in approximately 1 per cent of infants. Craniofacial abnormalities and developmental delay have been reported as well. Carbamazepine is found in breast milk, but its effects on the nursing infant are unknown.
(6, 32)
Carbamazepine is indicated for the treatment of simple partial, complex partial, and generalized tonic–clonic seizures. It is ineffec-tive against absence seizures, and may even exacerbate them. Carbamazepine is also indicated in the treatment of trigeminal neuralgia and other neuropathic pain syndromes. Several double-blind, placebo-controlled trials conﬁ  rm carbamazepine’s efﬁ  cacy 
in treating both the manic and mixed phase of bipolar disorder.
(33,34)
There is limited evidence demonstrating efﬁ  cacy in the treatment

(33,34)
There is limited evidence demonstrating efﬁ  cacy in the treatment 
of either bipolar or unipolar depression. Uncontrolled reports also suggest that carbamazepine may be useful in the treatment of personality disorders, impulse control disorders, and alcohol/sedative withdrawal syndrome.
Carbamazepine is contraindicated in patients with a history 
of previous bone marrow depression, hypersensitivity to the drug, or hypersensitivity to any of the tricyclic antidepressants (given its structural similarity to imipramine). Its use with monoamine oxidase inhibitors is not recommended, and carbam-azepine should be used with caution in patients with cardiac disease.
Given that carbamazepine is extensively metabolized by the liver and induces hepatic enzymes, it produces many significant drug–drug interactions (Table 6.2.6.2).
(35–37)  Many drug levels are

(35–37)  Many drug levels are 
reduced by carbamazepine and can become subtherapeutic. Therefore, it is important to monitor concomitantly administered medications, as dosage adjustments may be necessary.Effects of withdrawal
As with other antiepileptic drugs, carbamazepine should be gradually tapered over several weeks in order to avoid rebound seizures.
Carbamazepine is generally initiated at a starting dose of 100–400 mg, taken either as a single dose or two divided doses (see Table 6.2.6.1 for dosage forms). The dose is gradually increased by 100 or 200 mg every 2 weeks as the patient tolerates. The usual therapeutic serum concentration is 4–12 mg/l (20–50 μmol/l), 
which is meas ured before the ﬁ  rst morning dose. The half-life of Table 6.2.6.2 Carbamazepine (CBZ)-drug interactions

CBZ decreases drug levels Drugs that increase CBZ levels
Alprazolam Acetazolamide
Clobazam CimetidineClonazepam ClarithromycinClozapine DanazolDicoumarol Dextropropoxyphene
Doxycycline Diltiazem
Ethosuximide FluoxetineFentanyl Gemﬁ  brozilHaloperidol IsoniazidImipramine ItraconazoleLamotrigine KetaconazoleMesuximide LoratadineMethadone Macrolide antibiotics
Methylprednisolone Metronidazole
Oral contraceptives (can result in 
contraceptive failure)Nicotinamide
Nicotinic acid
PropoxypheneRemacemideRifampicin 
Stiripentol
TerfenadineValproateVerapamilViloxazinePancuronium
ParacetamolPhensuximidePhenytoin (can either increase 
or decrease)
PrednisolonePrimidoneRemacemide
Theophylline
TiagabineTopiramateValproateVecuroniumWarfarin
CBZ increases drug levels Drugs that decrease CBZ levels
Clomipramine (possibly) Cisplatin
Phenytoin (can either increase

Phenytoin (can either increase 
or decrease)Doxorubicin
Felbamate
RifampicinPhenobarbitalPhenytoinPrimidoneTheophyllinePrimidone

1235
carbamazepine will decrease with chronic administration due to 
autoinduction, necessitating frequent monitoring of the serum carbamazepine concentrations and continued dosage adjustment in the ﬁ  rst 2 months of therapy.
Laboratory screening
Given the risk of severe blood dyscrasias and hepatic failure, some 
authorities recommend obtaining a CBC and LFTs at the initiation of treatment. These tests are often repeated every 2 weeks for the ﬁ  rst few months of treatment, and then every 3 to 6 months 
thereafter. However, some authorities argue that testing is unneces-sary, since idiosyncratic reactions are rare and may occur too rapidly to be detected by routine laboratory monitoring.
Lamotrigine
Lamotrigine (Lamictal®) is a phenyltriazine compound, structur-ally unrelated to other antiepileptic drugs (see Fig. 6.2.6.1). It was introduced in Ireland in 1993 and in the United Kingdom and the United States in 1994.

Lamotrigine is thought to act by blocking voltage-sensitive sodium channels, and by inhibiting the release of glutamate. In experimen tal 
animal seizure models, it has an antiepileptic proﬁ  le similar to 
that of phenytoin and carbamazepine.
(38)
The oral bioavailability of lamotrigine approaches 100 per cent, and absorption is unaffected by food. Peak plasma concentrations are reached 2–3 h after an oral dose. The half-life of lamotrigine is approximately 30 h, but is altered by the presence of other anti-epileptic drugs (see Interactions). Plasma protein binding is approximately 55 per cent. Lamotrigine is metabolized by the liver to an inactive glucuronide conjugate, and then excreted in the urine. The clearance of lamotrigine may be reduced in patients with renal impairment and Gilbert’s syndrome, and these individu-als may beneﬁ  t from dosage reduction.
(39)
In general, lamotrigine has few side effects and is better tolerated

(39)
In general, lamotrigine has few side effects and is better tolerated 
than other antiepileptic drugs. The most common side effects include 
dizziness, headache, diplopia, ataxia, blurred vision, nausea, somno-lence, and rash. The most concerning side effect is skin rash, which can be life-threatening. Approximately 10 per cent of adults develop a rash while taking lamotrigine, but the majority of these are benign. However, about 1 in 1000 will develop a life-threatening rash, such as Stevens–Johnson syndrome or toxic epidermal necrolysis. The inci-dence of rash is much higher in paediatric patients, occurring in 1 in 50 to 1 in 100 patients; therefore, lamotrigine should be used with caution in patients less than 16 years of age. Starting at a low dose and slowly increasing it can minimize the risk of rash. Co-adminis-tration of valproate can increase the risk of rash. Given the difﬁ  culty

in predicting who will develop a life-threatening rash, lamotrigine is usually discontinued at the ﬁ  rst sign of any rash.
There are a few reports of possible idiosyncratic reactions in 
patients taking lamotrigine. These include disseminated intravas cularcoagulation, multiorgan failure, and acute hepatic necrosis.
(40) It is 
unclear, however, if these conditions were actually caused by the drug itself.
The few reported cases of overdose on lamotrigine (at doses up to 4000 mg) were not fatal, but resulted in symptoms such as excessive sedation, dizziness, and headache.
The effects of lamotrigine on human pregnancy and breast-fed infants are unknown.
Several double-blind, placebo-controlled, add-on trials conﬁ  rm 
lamotrigine’s efﬁ  cacy in treating some patients with partial or 
generalized tonic–clonic seizures.(39) Clinical trials also suggest

generalized tonic–clonic seizures.(39) Clinical trials also suggest 
efﬁ cacy against absence, atypical absence, and myoclonic seizures, 
as well as seizures associated with the Lennox–Gastaut syndrome.(41)
Lamotrigine demonstrated efﬁ  cacy in the treatment of bipolar 
depression in a large placebo-controlled trial.(42) However, it does 
not appear to be beneﬁ  cial in the treatment of acute mania, largely 
due to the drug’s long titration schedule. Several controlled studies have also demonstrated efﬁ  cacy in the maintenance treatment of 
(39, 43–45)  and in the rapid-cycling subtype of 
bipolar disorder.(46) In addition to bipolar depression, lamotrigine 
has shown some beneﬁ  t in two small placebo-controlled studies 
when added to selective serotonin reuptake inhibitors (SSRIs) as an augmentation strategy in the treatment of unipolar depression.
(47, 48)

(47, 48)
Preliminary evidence from two small placebo-controlled studies also indicates that lamotrigine may have beneﬁ  t as an augmenta-
tion therapy with conventional and atypical antipsychotics in treatment-resistant schizophrenia.
(49, 50)
Lamotrigine does not appear to affect the kinetics of other antiepileptic drugs or oral contraceptives, but its own kinetics are markedly affected by the concomitant administration of other antiepileptic drugs. Valproate inhibits the metabolism of lamo-trigine, resulting in a doubling of the half-life to almost 60 h. The enzyme-inducing antiepileptic drugs, such as carbamazepine and phenytoin, decrease the half-life to approximately 15 h. These interactions necessitate dosage adjustments when starting lamotrig-ine (see Dosage and Administration).
(38)

(38)
As with other antiepileptic drugs, lamotrigine should be tapered gradually over several weeks in order to avoid rebound seizures.
Lamotrigine must be started at a low dose and increased with caution to a therapeutic dosage in order to minimize the risk of rash. The patient should be informed of the risk of developing a rash, and instructed to contact the physician immediately if one appears. The starting dose depends upon the concomitant admin-istration of other antiepileptic drugs. See Tables 6.2.6.3–6.2.6.5 for the appropriate lamotrigine titration schedules. Table 6.2.6.1 shows dosage forms.6.2.6 antiepileptic drugs

SECTION 6  treatment methods in psychiatry 1236
T opiramate (T opamax®) is a sulfamate-substituted monosaccha-
ride originally developed as an oral hypoglycemic agent. It was sub-sequently found to have antiepileptic effects. It is currently approved for epilepsy in over 60 countries and for migraine prophylaxis in more than 20 countries.
T opiramate is believed to act through several different mechanisms including: (1) inhibition of sodium channel conductance; (2) inhi-bition of L-type calcium channels; (3) increase in GABA release through an unknown mechanism; (4) decrease in glutamate-mediated excitation through blockade of kainate receptors; and (5) inhibition of carbonic anhydrase.
(51)
There is almost complete, linear, and rapid absorption of topira-mate across dose ranges.
(52) The absorption of topiramate is not

(51)
(52) The absorption of topiramate is not 
affected by food. It is not signiﬁ  cantly protein-bound. Hepatic metabolism (~20 per cent) is less important than renal clearance 
(~80 per cent) and inactive metabolites comprise less than 5 per cent the administered dose.
(52) The normal half-life of topira-
mate is 19–23 h; this is not inﬂ  uenced by the administration of 
hepatic enzyme-inducing medications such as carbamazepine 
or phenytoin.(52)
The most common side effects of topiramate are memory and concentration difficulties, paresthesias, somnolence, dizziness, anorexia, and weight loss. In clinical trials with topiramate, kidney stones are reported 2–4 times more frequently than in the general

population, probably as a result of the drug’s inhibition of carbonic anhydrase. Patients predisposed to developing kidney stones should maintain good hydration during topiramate therapy to minimize the risk of renal stone formation. Rarely, topiramate has been associated with acute myopia precipitating secondary angle closure glaucoma and with oligohidrosis leading to hyperthermia.
Several cases of topiramate overdose have been recorded, with signs and symptoms including severe metabolic acidosis, convulsions, drowsiness, speech disturbance, blurred vision, diplopia, lethargy, tupor, hypotension, abdominal pain, agitation, and dizziness. The clinical consequences in most cases were not severe. However, deaths have occurred after poly-drug overdoses involving topiramate.
The effects of topiramate on human pregnancy and breast-fed infants are unknown.

T opiramate has conﬁ  rmed efﬁ  cacy as monotherapy for partial-
onset seizures or primary generalized tonic–clonic seizures for patients 10 years and older and as adjunctive therapy for the same seizure types, including seizures associated with Lennox–Gastault syndrome, in patients of age 2 and older.
(52) In addition, several 
large controlled studies have demonstrated beneﬁ  t in the prophy-
laxis of migraines.(53–55)  It may also be helpful in the treatment of 
essential tremor and chronic pain syndromes. There are no large placebo-controlled studies investigating the use of topiramate as monotherapy for bipolar disorder. However, there is limited evi-dence from several small open-label studies for topiramate as an adjunctive treatment for both the depressive
(56) and manic(57, 58)

phases of bipolar disorder. Controlled studies have demonstrated efﬁ cacy in eating disorders including binge eating disorder
(52) and 
bulimia nervosa.(59) Given its ability to reduce weight, the utility of 
topiramate may be greatest as an adjunctive treatment in bipolar disorder with comorbid obesity. Several small placebo-controlled studies have also suggested that topiramate may have beneﬁ  t in the 
treatment of alcohol dependence,
(60) impulse control disorders 
such as pathological gambling,(61) and borderline personality 
disorder.(62)
T opiramate does not typically alter the metabolism of any other drugs. One important exception to this is that the effectiveness of Table 6.2.6 .3 Suggested lamotrigine titration schedule for patients 
taking carbamazepine, phenytoin, phenobarbital, primidone, or rifampicin and not taking valproate
Week 1  25 mg daily

Week 2  50 mg dailyWeek 3 100 mg daily, in divided dosesWeek 4 100 mg daily, in divided dosesWeek 5 200 mg daily, in divided doses
Week 6 300 mg daily, in divided doses
Week 7 Up to 400 mg daily, in divided doses
Table 6.2.6 .4 Suggested lamotrigine monotherapy for patients not 
taking carbamazepine, phenytoin, phenobarbital, primidone, or 
rifampicin and not taking valproate
Week 1 12.5 mg daily
Week 2 25 mg dailyWeek 3 50 mg dailyWeek 4 50 mg dailyWeek 5 100 mg daily
Week 6 150 mg daily
Week 7 200 mg daily
Table 6.2.6 .5 Suggested lamotrigine titration schedule for patients 
taking valproate
Week 1 12.5 mg every other  day
Week 2 25 mg every other  day
Week 3 25 mg dailyWeek 4 25 mg dailyWeek 5 50 mg daily
Week 6 75 mg daily
Week 7 100 mg daily

1237
the ethinylestradiol component of oral contraceptives is reduced 
when more than 200 mg of topiramate is prescribed daily.(52)
T opiramate occasionally leads to a modest increase in phenytoin concentrations (0–25 per cent) and to modest increases in the clearance of risperidone, pioglitazone, and lithium.
(52)
Hydrochlorothiazide can lead to modest increases in serum concen-tration of topiramate.
(52) Concomitant administration of topira-
mate and valproate has been associated with hyper ammonemia with or without encephalopathy in patients who have previously tolerated either drug alone.
As with other antiepileptic drugs, topiramate should be tapered gradually over several weeks in order to avoid rebound seizures.

The recommended dose for monotherapy treatment of epilepsy in adults and children 10 years of age or older is 400 mg/day in two divided doses. It is recommended that therapy be initiated at 25–50 mg/day followed by titration to an effective dose in incre-ments of 25–50 mg/week. The recommended total daily dose for migraine prophylaxis is 100 mg/day administered in two divided doses. In patients with renal impairment one-half of the usual adult dose is recommended.
Other antiepileptics
Several other drugs with antiepileptic activity are currently under investigation in various psychiatric disorders, but have not as yet shown well-documented efﬁ  cacy. Gabapentin (Neurontin®), a

Several other drugs with antiepileptic activity are currently under investigation in various psychiatric disorders, but have not as yet shown well-documented efﬁ  cacy. Gabapentin (Neurontin®), a 
structural analog of gamma-aminobutyric acid (GABA), has been marketed for use as adjunctive therapy in the treatment of epilepsy since 1993 and also carries a clinical indication for postherpetic neuralgia. It displays a pharmacological proﬁ  le similar to phenytoin 
and carbamazepine in animal seizure models.
(63)
Several placebo-controlled trials conﬁ  rm gabapentin’s efﬁ  cacy as 
adjunctive therapy in some patients with partial seizures, especially complex partial seizures and partial seizures with secondary gener-alization.
(42) Additionally, several controlled studies have demon-
strated beneﬁ  t in the treatment of various pain syndromes, particu-
larly neuropathic pain.(64, 65)  In a large, multicentre, controlled

larly neuropathic pain.(64, 65)  In a large, multicentre, controlled 
study gabapentin failed as an adjunctive treatment with lithium and/or valproate in the treatment of acute manic or mixed episodes, and actually performed signiﬁ  cantly more poorly than placebo.
(66)
Since that time, however, a small controlled study has suggested 
that gabapentin may have efﬁ  cacy as an adjunctive maintenance 
treatment for bipolar disorder.(67) Two small controlled studies 
have also demonstrated efﬁ  cacy for gabapentin in the treatment of 
panic disorder(68) and social anxiety(69) respectively.
Oxcarbazepine (Trileptal®), the 10-keto analog of carbamaze-

pine, has an antiepileptic effect similar to carbamazepine, but has fewer side effects, and has not been associated with severe blood dyscrasias. The drug also has fewer effects on hepatic enzyme activ-ity, and hence causes fewer drug interactions. Given its similarity to carbamazepine, oxcarbazepine might be expected to be effective for the manic phase of bipolar disorder. However, despite some promising uncontrolled observations, there are as yet no large controlled trials of oxcarbazepine as monotherapy in adult bipolar disorder. A large double-blind study of oxcarbazepine in children 
with manic or mixed episodes did not demonstrate efﬁ  cacy.
(70)
Preliminary evidence from one small open-label study suggests 
that oxcarbazepine may also reduce the risk of relapse prevention in alcohol abuse.
(71)

(70)
(71)
Zonisamide (Zonegran®) is an antiepileptic that causes carbonic 
anhydrase inhibition; it is somewhat similar in its pharmacologic proﬁ le to topiramate. Like topiramate, it frequently causes weight 
loss, and has been shown effective for weight loss in a controlled study of obese individuals with binge eating disorder.
(72) It also 
increases the risk of kidney stones to at least the same degree as topiramate. Small open-label studies have suggested that zonisamide may be effective in the treatment of both the manic and depressed phases of bipolar disorder.
(73,74)
Tiagabine (Gabitril®) is believed to exert its anticonvulsant 
effects by enhancing the effects of GABA. This is thought to occur through blockade of reuptake of GABA into presynaptic neurones. Tiagabine showed efﬁ  cacy in the treatment of generalized anxiety

effects by enhancing the effects of GABA. This is thought to occur through blockade of reuptake of GABA into presynaptic neurones. Tiagabine showed efﬁ  cacy in the treatment of generalized anxiety 
disorder in a large double-blind study.
(75) In addition, several small 
open-label studies have demonstrated preliminary evidence beneﬁ  t 
in the treatment of posttraumatic stress disorder,(76) major depres-
sive disorder with comorbid anxiety,(77) and as an augmentation 
therapy for generalized anxiety disorder.(78) Tiagabine demonstrated 
limited efﬁ  cacy as an add-on treatment for treatment-refractory 
bipolar disorder in one small clinical case series.(79)
Levetiracetam (Keppra®) is a novel anticonvulsant with an 
unclear mechanism of action. It has demonstrated beneﬁ  t in the 
treatment of social anxiety disorder in one small controlled study, warranting further investigation into this potential use.
(80)
Pregabalin (Lyrica®) is a structural derivative of GABA. However,

(80)
Pregabalin (Lyrica®) is a structural derivative of GABA. However, 
it does not act by altering GABA levels or by binding to the GABA receptor. The exact mechanism of action of pregabalin is unknown, although it is most likely related to its high afﬁ  nity for the alpha
2-
delta site on voltage-gated calcium channels. Pregabalin has shown promise as an anxiolytic. Three separate large placebo-controlled studies have demonstrated beneﬁ  t with pregabalin in the treatment 
of generalized anxiety disorder.
(81–83)  Pregabalin also demonstrat-
ed efﬁ  cacy in the treatment of social anxiety disorder in one large 
controlled study.(84)
It is important to note that soon after the completion of this text,

It is important to note that soon after the completion of this text, 
the United States Food and Drug Administration released an alert recommending that patients taking antiepileptic drugs be closely monitored for changes in behavior that could indicate worsening of depression or the emergence of suicidal thoughts or behavior. This warning was based on a meta-analysis of placebo-controlled trials involving eleven antiepileptic medications, including both tri-als in epilepsy and trials in psychiatric disorders. This meta-analysis revealed that patients receiving antiepileptic drugs had approxi-mately twice the risk of suicidal behavior or ideation (0.43%) 
compared to patients receiving placebo (0.22%).
(85) Further investi-
gation and analyses of this possible association are ongoing.

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71. Croissant, B., Diehl, A., Klein, O., et al. (2006). A pilot study of 
oxcarbazepine versus acamprosate in alcohol-dependent patients. 
Alcoholism, Clinical and Experimental Research ,30(4), 630–5.
72. McElroy, S.L., Kotwal, R., Guerdjikova, A.I., et al. (2006). Zonisamide 
in the treatment of binge eating disorder with obesity: a randomized controlled trial. The Journal of Clinical Psychiatry ,67(12), 
1897–906.
73. McElroy, S.L., Suppes, T., Keck, P .E. Jr., et al. (2005). Open-label 
adjunctive zonisamide in the treatment of bipolar disorders: a prospective trial. The Journal of Clinical Psychiatry ,
66(5), 617–24.

74. Ghaemi, S.N., Zablotsky, B., Filkowski, M.M., et al. (2006). An open 
prospective study of zonisamide in acute bipolar depression. Journal of 
Clinical Psychopharmacology ,26(4), 385–8.
75. Pollack, M.H., Roy-Byrne, P .P ., Van Amerigen, M., et al. (2005). 
The selective GABA reuptake inhibitor tiagibine for the treatment of 6.2.6 antiepileptic drugs

SECTION 6  treatment methods in psychiatry 1240
generalized anxiety disorder: results of a placebo-controlled study. 
The Journal of Clinical Psychiatry ,66(11), 1401–8.
76. Connor, K.M., Davidson, J.R., Weisler, R.H., et al.  (2006). Tiagabine for 
posttraumatic stress disorder: effects of open-label and double-blind discontinuation treatment. Psychopharmacology ,184(1), 21–5.
77. Carpenter, L.L., Schecter, J.M., Tyrka, A.R., et al. (2006). Open-label 
tiagabine monotherapy for major depressive disorder with anxiety. The Journal of Clinical Psychiatry ,67(1), 66–71.
78. Schwartz, T.L., Azhar, N., Husain, J., et al. (2005). An open-label study 
of tiagabine as augmentation therapy for anxiety. Annals of Clinical 
Psychiatry ,17(3), 167–72.
79. Suppes, T., Chisholm, K.A., Dhavale, D., et al. (2002). Tiagabine in 
treatment refractory bipolar disorder: a clinical case series. Bipolar
Disorders ,4(5), 283–9.
80. Zhang, W., Connor, K.M., and Davidson, J.R. (2005). Levetiracetam

80. Zhang, W., Connor, K.M., and Davidson, J.R. (2005). Levetiracetam 
in social phobia: a placebo controlled pilot study. Journal of clinical 
Psychopharmacology ,19(5), 551–3.
81. Feitner, D.E., Crockatt, J.G., Dubovsky, S.J., et al. (2003). A randomized, 
double-blind, placebo-controlled, ﬁ  xed-dose, multicenter study of 
pregabalin in patients with generalized anxiety disorder. Journal of 
Clinical Psychopharmacology ,23(3), 240–9.
82. Rickels, K., Pollack, M.H., Feitner, D.E., et al. (2005). Pregabalin for 
treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Archives of General Psychiatry ,62(9), 1022–30.
83. Montgomery, S.A., T obias, K., Zornberg, et al.  (2006). Efﬁ  cacy and

83. Montgomery, S.A., T obias, K., Zornberg, et al.  (2006). Efﬁ  cacy and 
safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine. The Journal of Clinical 
Psychiatry ,67(5), 771–82.
84. Pande, A.C., Feitner, D.E., Jefferson, J.W., et al. (2004). Efﬁ  cacy of the 
novel anxiolytic pregabalin in social anxiety disorder: a 
placebo-controlled, multicenter study. Journal of Clinical 
Psychopharmacoly ,24(2), 1419.
85.  United States Food and Drug Administration (January 31, 2008). 
Information for Healthcare Professionals - Suicidality and Antiepileptic Drugs.
6.2.7 Drugs for cognitive disorders
Cognitive disorders are among the most difﬁ  cult of all nervous

Cognitive disorders are among the most difﬁ  cult of all nervous 
system illnesses to treat as they affect the most complex and least clearly understood aspects of brain function. Animal studies can-not accurately mirror the complexities of human cognition, and there are few, if any, animal models of human cognitive illnesses. As so few drugs have been found to exert clinically signiﬁ  cant 
effects, animal models for testing novel cognition-enhancing agents have unknown predictive value. However, progress has been made in recent years with improved international agreement on the criteria used to approve new cognition-enhancing drugs, and the introduction of new drugs for the treatment of dementia.
It is important to deﬁ  ne the objective of drug treatment in this, the 
most common of all forms of senile dementia. Alzheimer’s disease (AD) is a progressive illness; drug treatment could treat the symp-

toms without inﬂ  uencing the course of the disease, or it might seek 
to delay or arrest the progressive cognitive deterioration which such patients suffer. Although the latter aim is the subject of inten-sive research in academic and industrial laboratories,
(1) there are 
no drugs that target the underlying pathology, and only palliative treatments are, as yet, available.
The approval of new medicines for the symptomatic treatment 
of AD in recent years has led regulatory agencies to deﬁ  ne more 
clearly what criteria should be used in assessing the clinical beneﬁ  ts

clearly what criteria should be used in assessing the clinical beneﬁ  ts 
derived from drug treatment. AD is a disease characterized by dis-turbances in higher cortical function, including disorders of recent memory, language function, praxis, visual perception, abstract thinking, and decision making. A variety of composite dementia assessments designed to provide an overall summary of cognitive status, for example the Mini Mental State Examination ( MMSE ), 
Alzheimer’s Disease Assessment Scale-Cognition ( ADAS-Cog ), and 
the Brief Cognitive Rating Scale are used.
(2) Most studies w ith cho-
linesterase inhibitors in AD have used ADAS-Cog (a 70-point scale), 
and a two to three-point improvement for the drug-treated group versus placebo at 6 months has generally been accepted. However, statistically signiﬁ  cant, but small, drug-induced improvements in

and a two to three-point improvement for the drug-treated group versus placebo at 6 months has generally been accepted. However, statistically signiﬁ  cant, but small, drug-induced improvements in 
cognitive assessment scores do not necessarily represent a clinically signiﬁ  cant improvement to the patient or to their doctor; they 
must be supplemented by evidence of clinical improvement, using some form of Clinical Global Impression of Change as an outcome measure, usually rated by a clinician on a seven-point scale.
The development of agreed scientiﬁ  c and clinical standards for 
the approval of new drugs has largely eclipsed most of the older drugs that had been used in the treatment of AD and other demen-tias, since none of them can meet these standards. The older drugs include a range of cerebral vasodilators (e.g. dihydroergotoxin, 
papaverine, isoxsuprine, cinnarizine) and the so-called ‘nootropics’

papaverine, isoxsuprine, cinnarizine) and the so-called ‘nootropics’ 
(e.g. piracetam, oxiracetam, aniracetam), which were widely used in some European countries, as well as the so-called ‘metabolic enhancers’ (e.g. idebenone and indeloxazine) which were popular for a while in Japan.
Cholinergic agents
Attention has focused instead on the cholinergic agents. The ‘cholinergic hypothesis’ of dementia. was boosted by the discovery in the 1970s that cholinergic neurones are particularly damaged or absent from the brains of patients dying with AD, and that the extent of damage to the cholinergic system correlates with the severity of dementia in life.
(3) In AD the damage appears to be 
particularly severe in the system of cholinergic neurones located deep in the forebrain in the nucleus basalis of Meynert, whose ﬁ bres branch extensively and innervate most areas of the cerebral

particularly severe in the system of cholinergic neurones located deep in the forebrain in the nucleus basalis of Meynert, whose ﬁ bres branch extensively and innervate most areas of the cerebral 
cortex. This neuronal system forms part of the ascending reticular activating system, which plays a key role in the process of selective attention—essential for the laying down of new memories. Consequently, there has been considerable interest in the possibility that ‘cholinergic replacement therapy’ might relieve the symptoms of AD, in the same way that dopamine replacement therapy has successfully been employed in the treatment of Parkinson’s disease. The most successful approach so far has been the use of inhibitors of the enzyme acetylcholinesterase.
Inhibitors of acetylcholinesterase  have been known since the 
nineteenth century with the discovery of physostigmine, a plant

1241
product used as an arrow-tip poison. Irreversible organophosphate 
inhibitors of acetylcholinesterase were later developed as chemical warfare agents (‘nerve gases’), and for more peaceful uses as insecticides. Despite their colourful past, low doses of this class of compounds have proved effective as cognitive enhancers in a wide range of animal tests, including those in which cholinergic function is deliberately impaired.
(4) The ﬁ  rst clinical trials in patients with 
AD were performed with physostigmine, and conﬁ  rmed that the 
drug had signiﬁ  cant beneﬁ  cial effects on cognitive performance 
in AD patients.(5) However, it has limited usefulness because, 
although it is absorbed rapidly, it has only a very short half-life in plasma. This means that to obtain any sustained cognitive beneﬁ  t 
it has to be given in doses that are sufﬁ  ciently high to elicit a num-
ber of adverse side-effects; thus, the therapeutic window was very narrow.

Subsequently four other cholinesterase inhibitors with improved 
proﬁ les have gained approval for use in AD: tacrine ,donepezil, 
rivastigmine, and galantamine , but tacrine is no longer actively 
marketed owing to liver toxicit y. Clinical data from  sever al thou sand
patients with AD involved in trials with these cholinesterase inhibi-tors are now available.
(6–8) The ﬁ  rst of these to gain approval in 
1997 was donepezil. Results of large-scale clinical trials with done-zepil and the other cholinesterase inhibitors over periods of 15 and 24 weeks have yielded similar results for the three compounds in patients with mild to moderately severe AD. The drugs caused small but signiﬁ  cant improvements in the ADAS-Cog, CIBIC, and

MMSE scores. The most common side-effects were transient mild nausea, insomnia, and diarrhoea. Not all patients with AD will beneﬁ  t from treatment with cholinesterase inhibitors; the propor-
tion ranges from 30 to 50 per cent; although the clinical beneﬁ  ts 
of drug treatment in patients showing a response can persist for up to 24 months.
The approval of cholinesterase inhibitors for the treatment of 
Alzheimer’s disease was an important landmark. They are reasonably 
well tolerated and produce signiﬁ  cant, if modest, beneﬁ  cial effects 
in patients with mild to moderately severe AD. However, they have not gained immediate and universal acceptance. In some countries (e.g. the United Kingdom) it has been argued that the drugs are too costly and provide at best only a modest improvement.
Some studies have also found the cholinesterase inhibitors to be 
effective in treating the cognitive deﬁ  cits in vascular dementias, but

effective in treating the cognitive deﬁ  cits in vascular dementias, but 
the effects are small and less consistent. Rivastigmine has also been shown to have beneﬁ  cial effects in treating the cognitive deﬁ  cits in 
Parkinson’s disease with dementia.
(9) The cholinesterase inhibitors 
may thus ﬁ  nd other applications as cognitive enhancers in condi-
tions other than AD.
An alternative approach to cholinergic replacement therapy has 
been to develop drugs that mimic acetylcholine  and act as agonists 
at the muscarinic cholinergic receptors in brain, but which, unlike 
acetylcholine itself, are bioavailable and brain-penetrant. Attention 
has focused on the discovery and development of muscarinic agonists that show selectivity for the m
1-receptor subtype, which is

1-receptor subtype, which is 
the predominant form present in the cerebral cortex. The most thoroughly studied cholinomimetic to date is xanomeline, a compound that acts as a highly potent and selective m
1-receptor 
agonist. Clinical effects were assessed in a multicentre study of 343 patients with AD.
(10) Patients on the highest dose showed 
signiﬁ  cant improvement when assessed using the ADAS-Cog scale 
and also showed a signiﬁ  cant overall global improvement using CIBIC. In addition to cognitive improvements, patients receiving 
xanomeline also exhibited signiﬁ  cant behavioural improvement, 
with dose-dependent reductions in vocal outbursts, suspiciousness, delusions, agitation, and hallucinations. Xanomeline is unlikely

with dose-dependent reductions in vocal outbursts, suspiciousness, delusions, agitation, and hallucinations. Xanomeline is unlikely 
to be used in the treatment of AD because of its relatively short duration of action, but these results suggest that further research on cholinomimetics may still be justiﬁ  ed.
An entirely different pharmacological approach is exempliﬁ  ed by 
the drug memantine , the ﬁ  rst to be approved for the treatment of 
moderate to severe AD. Memantine is thought to act by virtue of its ability to block the NMDA sub-type of glutamate receptors in the brain. Clinical trials in AD showed small but signiﬁ  cant beneﬁ  -
cial effects on cognitive tests and in global clinical outcome, but curiously the effects were most notable in patients with advanced stage disease and less in patients with mild to moderate AD.
(11)

(11)
Although the effects of memantine are small, it remains the only effective treatment for advanced stage AD.
Attention-deﬁ  cit hyperactivity disorder
Attention-deﬁ  cit hyperactivity disorder ( ADHD ) is one of the 
most thoroughly studied disorders in child psychiatry, and the increasingly common use of stimulant drugs to treat this disorder has become the focus of much public attention and debate in recent years.
(12) ADHD is deﬁ  ned in terms of three key features: lack of 
sustained attention, impulsivity, and hyperactivity. According to the DSM-IV deﬁ  nition the diagnosis of ADHD now includes more 
than 10 per cent of children.
(13)
Because of the interest in the drug treatment of ADHD, a num-

(13)
ber of assessment tools have been developed. These include the widely used Conners’ T eacher Rating Scale, the Conners’ Parent Rating Scale, and a variety of tests designed to measure hyperactiv-ity, problem behaviour, attention, and other aspects of cognition, as well as academic performance.
(14)
The most commonly used drugs are the psychostimulants 
amfetamine  and methylphenidate . Methylphenidate (Ritalin®) is 
by far the most widely prescribed. In more than 100 published trials these drugs have been found to have signiﬁ  cant beneﬁ  cial 
effects on all three key symptoms of ADHD in approximately 70 per cent of the treated children, and also in an adult form of ADHD.
(15) Amfetamine (Adderall®) is approved for treatment of 
adult ADHD (not licensed in UK).
The mechanism of action of all three agents is similar; they

The mechanism of action of all three agents is similar; they 
act principally as inhibitors of the dopamine-uptake mechanism in the brain and promote the release of this neurotransmitter, thus stimulating dopaminergic mechanisms. The drugs also act to an important extent on noradrenaline-containing neurones to promote an increased release of this monoamine.
(16) This may be relevant;a 
selective inhibitor of the noradrenaline transporter in brain, atom-
oxetine , has been approved as the ﬁ  rst non-scheduled stimulant 
for the treatment of ADHD in both children and adults.(17)
Another non-amfetamine modaﬁ  nil is also non-scheduled and 
is widely used in the United States for the treatment of ADHD,(18)

although the drug has not yet gained regulatory approval from FDA because of possible serious adverse skin reactions. The mode of action of modaﬁ  nil is unknown but it is used for the treatment of 
narcolepsy.
It is paradoxical that stimulant drugs, whose actions include 
an ability to promote hyperactivity, should have a calming effect 6.2.7 drugs for cognitive disorders

SECTION 6  treatment methods in psychiatry 1242
on hyperactive children. One explanation is that actions of these 
amfetamine derivatives show the ‘rate dependency’ typical of other central nervous system agents, i.e. they tend to stimulate low rates of behaviour and to suppress high rates.
(19) An alternative view is 
that the relatively low doses of amphetamines used in the treat-
ment of ADHD would not have stimulant effects even in normal healthy adults. There are few animal models that can be used in the study of psychostimulant use or ADHD. Mice that are genetically engineered to delete the genes for the dopamine and other monoamine transporters have proved valuable.
(20) Animals 
which lack the dopamine transporter have elevated levels of dopamine in their brains and are behaviourally hyperactive. Paradoxically, d-amfetamine decreases activity in these animals, in keeping with the ‘rate-dependency’ hypothesis.
(20)
The use of amfetamines, particularly methylphenidate, has

(20)
The use of amfetamines, particularly methylphenidate, has 
increased rapidly during the past 30 years, particularly in the United States where in some states more than 10 per cent of school-age boys receive the drug.
(12) The use of amfetamines in Europe 
has been at a much lower level so far, although their use in ADHD has also been increasingly rapidly.
(12) I n  t u rn ,  s u c h  wi d e s p r e ad  
use of psychostimulants creates problems about diversion and abuse.
(12)
‘Cognition Enhancers’ in Drugs Futures 2025—[www.foresight.gov.uk/
Brain_Science_Addiction].
‘Drug Treatment of Alzheimer’s Disease’ , Royal College of Psychiatry—
[www.rcpsych.ac.uk/mentalhealthinformation/olderpeople/
drugtreatmentofalzheimers.aspk].
‘Methylphenidate, atomoxetine and dexamfetamine for attention deﬁ  cit 
hyperactivity disorder (ADHD) in children and adolescents—guidelines.’ National Institute for Clinical Excellence UK, March 22, 2006. [http://www.nice.org.uk].

1. Moreira, P .I., Zhu, X., Nunomura, A., et al.  (2006). Therapeutic 
options in Alzheimer’s disease. Expert Review of Neurotherapeutics ,
6, 897–910.
2. Gershon, S., Ferris, S.H., Kennedy, J.S., et al. (1994). Methods for the 
evaluation of pharmacological agents in the treatment of cognitive 
and other deﬁ  cits in dementia. In Clinical evaluation of psychotropic 
drugs: principles and guidelines  (eds. R.F. Prien and D.S. Robinson), 
pp. 467–99. Raven Press, New Y ork.
3. Bartus, R.T., Dean, R.L., Beer, B., et al.  (1982). The cholinergic 
hypothesis of geriatric memory dysfunction. Science ,217, 408–17.
4. Rupniak, N.M.J., Steventon, M.J., Jennings, C.A., et al.  (1989). 
Comparison of the effects of four cholinomimetic agents on cognition in primates following disruption by scopolamine. Psychopharmacology ,

99, 189–95.
5. Giacobini, E. (1998). Cholinesterase inhibitors for Alzheimer’s 
disease therapy: from tacrine to future applications. Neurochemistry 
International ,32, 413–19.
6. Birks, J. and Harvey, R.J. (2006). Donepezil for dementia due to 
Alzheimer’s disease. Cochrane Database Systematic Reviews , (1), 
CD001190.
7. Loy, C. and Schneider, L. (2004). Galantamine for Alzheimer’s disease. 
Cochrane Database Systematic Reviews , (4), CD001747.
8. Birks, J., Grimley Evans, J., Lakovidou, V ., et al.  (2006). Rivastigmine 
for Alzheimer’s disease. Cochrane Database Systematic Reviews , (4), 
CD001191. 9. Maidment, I., Fox, C., and Boustani, M. (2006). Cholinesterase 
inhibitors for Parkinson’s disease dementia. Cochrane Database 
Systematic Reviews , (1), CD004747.
10. Bodick, N.C., Offen, W.W., Levey, A.I., et al. (1997). Effects of

10. Bodick, N.C., Offen, W.W., Levey, A.I., et al. (1997). Effects of 
xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptom in Alzheimer’s disease. Archives of 
Neurology ,54, 465–73.
11. McShane, R., Areosa Sastre, A., and Minakaran, N. (2006). Memantine 
for dementia. Cochrane Database Systematic Reviews , (2), CD003154.
12. Iversen, L.L. (2006). Speed, ecstasy, ritalin: the science of amphetamines .
13. American Psychiatric Association. (2000). Diagnostic and statistical 
manual of mental disorders  (4th edn, T ext Revision) (DSM-IV-TR). 
14. Conners, C.K. (1998). Rating scales in attention deﬁ  cit hyperactivity 
disorder: use in assessment and treatment monitoring. The Journal of 
Clinical Psychiatry ,59(Suppl. 7), 24–30.

15. Wender, P .H. (2001). ADHD: attention-deﬁ  cit hyperactivity disorder in 
children, adolescents and adults . Oxford University Press, Oxford.
16. Solanto, M.V . (1998). Neuropsychopharmacological mechanism of 
stimulant drug action in attention-deﬁ  cit hyperactivity disorder: a 
review and integration. Behavioural Brain Research ,94, 127–52.
17. Kratochvil, C.J., Vaughan, B.S., Daughton, J.M., et al.  (2004). 
Atomoxetine in the treatment of attention deﬁ  cit hyperactivity 
disorder. Expert Review of Neurotherapeutics ,4, 601–11.
18. White, R.F. and Giorgadze, A. (2006). A randomized, double-blind, 
placebo-controlled study of modaﬁ  nil ﬁ  lm-coated tablets in children 
and adolescents with attention-deﬁ  cit hyperactivity disorder.

and adolescents with attention-deﬁ  cit hyperactivity disorder. 
45, 503–11.
19. Robbins, T.W. and Sahakian, B.J. (1979). Paradoxical effects of 
psychomotor stimulant drugs in hyperactive children from the standpoint of behavioural pharmacology. Neuropharmacology ,
18, 931–50.
20. Gainetdinov, R.R., Sotnikova, T.D., and Caron, M.G. (2002). 
Monoamine transporter pharmacology and mutant mice. Trends in 
Pharmacological Sciences ,23, 367–73.
6.2.8 Drugs used in the 
treatment of the addictions
Medical treatment of the addictions remains controversial, with

Medical treatment of the addictions remains controversial, with 
addiction itself viewed as a lifestyle problem, a hijacking of brain systems by drugs, or as a medical illness. Many of these controversies may be avoided by taking a goal-oriented approach to treatment, in which clinical objectives are deﬁ  ned, and both medications and 
psychological interventions are used to facilitate progress towards these. The effectiveness of medications is maximized when they are used as one component of a comprehensive treatment plan.
There are no ‘magic bullets’ in addiction treatment—the same

There are no ‘magic bullets’ in addiction treatment—the same 
pharmacological principles apply to these drug treatments as to any other. Drugs need to be given in effective doses, at appropriate intervals, allowed time to reach steady state, and also to dissipate when terminated on the basis of their half-life. Some drugs also have an abuse potential of their own (e.g. opiates, sedative-hypnotics) especially those with a rapid onset of action, and such

1243
drugs need to be particularly closely monitored and controlled, 
to minimize their diversion and misuse.
Medications in perspective
The clinical goal-oriented approach requires clarity about the clini-cal objectives at each phase of the treatment process. A typical treatment plan involves three primary clinical objectives:
◆ drug and psychosocial stabilization
◆ detoxiﬁ  cation when appropriate
◆ prevention of relapse or recurrence.
Stabilization with a substitution treatment (e.g. methadone

Stabilization with a substitution treatment (e.g. methadone 
or buprenorphine in opiate addiction) involves prescribing a pharmacological equivalent to the abused drug to stop illicit use, crime, etc. It allows time for stabilization to occur and to con-sider later objectives. Stabilization itself may be either short-term with the primary goal of terminating illicit drug use ‘on top’ of the prescription, or longer-term where it is commonly known as maintenance. The goals of maintenance are either psychosocial stabilization in preparation for detoxiﬁ  cation, or harm reduction 
in patients where abstinence is not practicable or safe. Unless a sufficient degree of stabilization has been achieved prior to detoxiﬁ  cation, the chances of success are strictly limited. The

in patients where abstinence is not practicable or safe. Unless a sufficient degree of stabilization has been achieved prior to detoxiﬁ  cation, the chances of success are strictly limited. The 
harm-reduction goal has generated much controversy, but one of its major beneﬁ  ts is the reduction in the spread of HIV among 
injecting drug users. In this group stable long-term maintenance treatment is preferable to repeated cycles of premature discontinu-ation followed by relapse to uncontrolled drug use with its atten-dant elevated risk of death from overdose as tolerance wanes. Monitoring by using drug screens and clinical assessments 
is required to ensure that patients do not use ‘on top’ of their 
prescription.
Speciﬁ  c drugs used in addiction treatment
This chapter deals with methadone, levacetylmethadol (LAAM), 
codeine and dihydrocodeine tartrate, buprenorphine, clonidine, lofexidine, naltrexone, naloxone, acamprosate, disulﬁ  ram, and clo-

methiazole (chlormethiazole), and covers addiction indications only. Many of these drugs are not licensed for use in addiction treatment (e.g. methadone tablets and injection), or are currently licensed in only one or a few countries (e.g. clonidine in Germany, lofexidine in the United Kingdom).
Methadone(1,2) (Methadose ®, Physeptone ®, 
Synastone ®)
This is a long-acting opioid analgesic which has been the mainstay 
of opioid substitution treatment, but is often difﬁ  cult to stop due 
to its prolonged withdrawal syndrome.
Pharmacology : it is a strong full μ-opioid agonist.
Types of compounds available : it is available in liquid, injectable, 
and tablet formulations.
Pharmacokinetics :tmax 2 to 4 h after oral dosing; 1 h after intra-
muscular injection; its half-life is 25 h.

Side-effects : as with other μ-opioids, its side-effects include 
mental blunting, sweating, constipation, nausea, and analgesia.T oxic effects : acute overdose leads to respiratory depression and 
pulmonary oedema.
Indications : opiate maintenance, stabilization, and detoxiﬁ  cation; 
it is also indicated for use during pregnancy.
Contraindications : respiratory or severe liver disease, mono-
amine oxidase inhibitors; caution should be exercised in elderly people.
Interactions : respiratory depression especially in combination 
with other sedative drugs; metabolism affected by hepatic enzyme induction and inhibition; plasma levels are affected by HAART drugs.
Effects of withdrawal : these include moderate but prolonged 
abstinence syndrome, especially poor sleep.
Dosage and administration : single daily dose, occasionally twice

Dosage and administration : single daily dose, occasionally twice 
daily; dose depends on the level of dependence—if unknown, ini-tially 10 to 20 mg daily. The minimum dose that covers withdrawal symptoms for 24 h should be given, and increased by 5 to 10 mg as necessary. Close monitoring is necessary by clinical assessment and 
drug screen. Some centres use intravenous preparations in those 
who don’t respond to oral preparations.
LAAM(3) (ORLAAM ®)
LAAM is a methadone variant with a much longer half-life, requiring only three visits a week for full supervision of medica-tion. However, take-home medication is not allowed and its use is restricted to specialist clinics and is reserved for patients who have failed other treatments. Its licence in Europe has been withdrawn due to QTc prolongation.
Pharmacology : it is a synthetic μ-opioid agonist with active

Pharmacology : it is a synthetic μ-opioid agonist with active 
metabolites which are more potent than the parent drug.
Types of compounds available : aqueous solution.
Pharmacokinetics :t
max 2 to 4 h; duration of action is 48 to 72 h; 
half-lives for LAAM and its metabolites are 2 to 4 days; it takes 2 weeks to reach steady state.
Side-effects : too rapid escalation of the dose may result in 
sedation, orthostatic hypotension, poor concentration, and over-dose.
T oxic effects : as for methadone; QTc prolongation; overdose 
occurs with too frequent (daily) dosing, use of multiple drugs, or ‘on-top’ use due to impatience with its slow onset of action.
Indications : opiate maintenance, stabilization, and detoxiﬁ  cation.
Contraindications : pregnancy (transfer to methadone); QTc 
prolongation prior to induction of treatment; dose should be reduced in elderly people, and in renal and hepatic impairment.
Interactions : as for methadone; other drugs prolonging QTc 
interval.

interval.
Effects of withdrawal : as for methadone, but with a milder 
withdrawal syndrome due to longer t
1/2.
Dosage and administration : pre-treatment ECG to identify 
prolonged QTc intervals, repeated 12–14 days after initiating treatment and periodically thereafter to rule out alterations to the QTc; give three times a week or on alternate days; increase dose by 20 to 40 per cent when transferring form 48 h to 72 h dosing inter-val. Transfer methadone to LAAM by giving 1.2 to 1.3 times the daily methadone dose; and LAAM to methadone by waiting at least 48 h and then giving 0.8 times the LAAM dose. If low or unknown tolerance, the initial dose is 20 to 40 mg three times weekly. Adjust dose in 5- to 10-mg steps, but no more frequently than 6.2.8 drugs used in the treatment of the addictions

SECTION 6  treatment methods in psychiatry 1244
weekly at the most. Strongly warn patients of the risk of supple-
mentation with street drugs especially prior to steady state. LAAM is detected by urine screens for methadone.
Buprenorphine(4,5) (Subutex®, Suboxone®, 
Temgesic®, Buprenex®)
Advantages over methadone and other full μ-agonists are its safety 
in overdose, the attenuation of the drug ‘high’ during on-top use, and its low levels of psychological reinforcement and withdrawal symptomatology during detoxiﬁ  cation.
Pharmacology : a partial μ-opioid agonist, which explains the 
ceiling on respiratory depression; slow onset of action; dissociates slowly from the μ-receptor.
Types of compounds available : 0.2-, 0.4-, 2- or 8-mg sublingual 
tablets, or 0.3-mg ampoules for injection; it is also available in combination with naloxone in a 1:4 ratio (Suboxone®) to reduce misuse if diverted.
Pharmacokinetics : sublingual tablets absorbed rapidly into

Pharmacokinetics : sublingual tablets absorbed rapidly into 
the buccal mucosa and released slowly into the blood stream; t
max 2 
to 6 h.
Side-effects : withdrawal symptoms if either too little or too 
much is given; nausea and vomiting are rare in addicts.
T oxic effects : as for methadone, but less constipation and 
respiratory depression.
Indications : opiate maintenance, stabilization, and detoxiﬁ  cation, 
including in pregnancy; may be especially suitable for opioid antagonist-assisted withdrawal; no dosage adjustment needed in renal failure or elderly people.
Contraindications : severe respiratory disease; use with care in 
severe liver disease.
Interactions : rare; sedation with benzodiazepines.
Effects of withdrawal : there is a mild but delayed withdrawal 
syndrome.
Dosage and administration : initial dose is 0.8–4 mg increasing

syndrome.
Dosage and administration : initial dose is 0.8–4 mg increasing 
by 4 to 8 mg daily until the required dose level is reached; usual daily dose 8 to 32 mg; doses above 12 mg may be given on alternate days; minimize withdrawal symptoms after long-term use by reducing by 1 mg every 3 to 4 days or less often; buprenorphine-assisted heroin detoxiﬁ  cation by rapid reduction over 5 to 10 days; 
the injectable form is not recommended for use in addiction treat-ment. Monitor clinical state and perform drug screens for compli-ance and on-top use.
Codeine phosphate and dihydrocodeine 
tartrate(6, 7) (DF118 Forte ®, 
DHC Continus ®)
Advantages over methadone occur in situations where long-acting

Advantages over methadone occur in situations where long-acting 
opioids may be inappropriate. These are often preferred by patients, and by doctors treating the young, low-dose users, and in acute situations (e.g. in police custody). Disadvantages are its ease of misuse, high levels of psychological reinforcement due to its rapid onset of action, and its unfavourable side-effect proﬁ  le.
Pharmacology : it is a weak short-acting μ-opioid agonist.
Types of compounds available : Codeine: 15-, 30- and 60-mg 
oral tablets, linctus, syrup and injection; dihydrocodeine tartrate: 30- or 40-mg oral tablets for use three to six times a day, and a 60-, 90-, or 120-mg slow-release preparation (DHC Continus) for 
use every 12 h; also parenteral preparation and elixir.
Pharmacokinetics : peak plasma levels at 1 to 2 h; half-life 3.5 
to 4.5 h.
Side-effects : it is more likely to cause sedation, dizziness, stimu-

to 4.5 h.
lation, euphoria, constipation, histamine release, psychomimetic effects, and disturbing dreams than other opioids.
T oxic effects : precipitation of life-threatening exacerbations of 
asthma; in overdose, coma with myotonic twitching, grand mal convulsions, and rarely rhabdomyolysis may occur.
Indications : opiate maintenance, stabilization, and detoxiﬁ  cation
Contraindications : acute exacerbations of asthma, lower respi-
ratory tract infection, respiratory depression, and hepatic failure, increased intracranial pressure; caution should be exercised in renal impairment and elderly people.
Interactions : as for methadone; it may enhance the effects of 
warfarin.
Effects of withdrawal : mild withdrawal syndrome.
Dosage and administration : dose depends on level of dependence;

warfarin.
Dosage and administration : dose depends on level of dependence; 
monitor clinical state and urine screen to conﬁ  rm compliance and 
termination of on-top use.
Naltrexone(8–11)  (Nalorex ®, Opizone ®)
Naltrexone is used to maintain abstinence in detoxiﬁ  ed opiate 
addicts during the period of highest vulnerability to relapse following detoxiﬁ  cation. It blocks the ‘high’ produced by opiates 
and promotes the extinction of conditioned responses. It also has a role in alcohol misuse and ultra-rapid opioid detoxification. Nalmefene is a related long-acting μ receptor antagonist that has a 
licence for alcoholism in some countries.
Pharmacology : it is a long-acting non-selective opioid antago nist.
Type of compound available : 50-mg oral tablet.
max 1 h; duration of action is dose related, 
and a single dose can be effective for up to 48 h.

Side-effects : opiate withdrawal syndrome may occur on induc-
tion; occasionally, gastrointestinal irritation, headaches, arthralgia, ﬂ attening of mood, and rash occur.
T oxic effects : severe opioid withdrawal in dependent addicts 
lasting 2 days; reversible liver toxicity at high dose in obese and elderly people; liver function tests should be monitored especially if baseline tests are impaired.
Indications : prevention of impulsive relapse following detoxiﬁ  -
cation in opioid users; opioid antagonist-assisted withdrawal; it reduces the reinforcing effects of alcohol.
Contraindications : acute hepatitis or liver failure, and 
active peptic ulcer; caution should be exercised in hepatic or renal impairment.
Interactions : competitive opioid blockade, so potentially can be 
overcome using very high opiate doses.

Effects of withdrawal : none, but risk of opioid overdoes follow-
ing withdrawal (loss of toerance).
Dosage and administration : treatment initiated following 
LFTs and opioid-negative urine screen (or a negative naloxone challenge). Twenty-ﬁ  ve mg is given on the ﬁ  rst day, and then 50 mg 
daily for 3 to 6 months. Thrice weekly dosing (100/100/150 mg) may occasionally improve compliance. Supervision of consump-tion by a supportive person, urine tests to monitor compliance, and 
regular reviews are very important in maximizing effectiveness.

1245
Naloxone(12) (Narcan ®)
Naloxone is a short-acting antagonist used in the treatment of 
opioid overdose, during detoxiﬁ  cation, and naltrexone induction. 
Take home naloxone may be used to treat opiate overdoses in the community by patients trained in its use.
Pharmacology : it is a short-acting competitive opioid antago nist.
Types of compounds available : it is available in injectable form 
for intramuscular, intravenous, or subcutaneous use.
Pharmacokinetics : half-life 1 to 2 h.
Side-effects : withdrawal in opiate-dependent subjects; nausea 
and vomiting; rarely, high blood pressure and pulmonary oedema can occur.
T oxic effects : very occasional deaths due to acute pulmonary 
oedema, extreme hypertension, and ventricular arrhythmias have occurred in those with known myocardial disease.
Indications : naloxone reverses the effects of opioid overdose,

Indications : naloxone reverses the effects of opioid overdose, 
and in high doses may help in overdose due to alcohol and benzo-diazepines. Naloxone is also occasionally used as the diagnostic test of opioid dependence, and as a challenge test prior to naltrex-one initiation. It is also used for opioid antagonist-assisted with-drawal, and in combination with oral opiate agonists to reduce misuse by the injectable route (e.g. Suboxone®). In neonates it is used for the reversal of the effects of opioids given to mothers 
during labour.
Contraindications : none if not opioid dependent (safe in 
neonates, children, pregnancy, elderly people); caution is advisable 
in opioid dependence, painful conditions, and cardiovascular disease.
Interactions : severe hypertension following reversal of coma due 
to clonidine overdose.
Effects of withdrawal : none.

Dosage and administration : in opioid overdose, give 0.4 to 2 mg 
intravenously (5 to 10 μg/kg in neonates and children) and repeat at 2- to 3-min intervals until desired response; may also be given intramuscularly in overdose; lower doses are used in adults (0.1–0.2 mg) to reverse opioid-induced respiratory depression, but higher doses are needed with buprenorphine and σ-receptor agonists. Continue naloxone by infusion or repeated 
injection if necessary to maintain recovery. During naltrexone induction, give 0.2 mg parenterally followed by 0.8 mg 30 min later (or 0.6 mg 30 s later if given intravenously). In equivocal cases give 1.6 mg.
Clonidine hydrochloride(13, 14)  
(Catapres ®, Dixarit ®)
Clonidine is an α2-adrenoceptor agonist used to suppress some

Clonidine is an α2-adrenoceptor agonist used to suppress some 
symptoms of opioid withdrawal, especially methadone-assisted withdrawal. It is ineffective for subjective symptoms, muscle/bone aches, stomach cramps, and insomnia.
Pharmacology : clonidine is an antihypertensive agent 
that decreases central and peripheral (sympathetic) noradren-ergic activity by stimulating presynaptic receptors in the locus coeruleus.
Types of compounds available : it is available as tablet, liquid, 
sustained release capsule, and transdermal preparation; the tablet 
is licensed in Germany.
max 90 min; half-life of 20 to 25 hSide-effects : it causes hypotension, sedation, dry mucous 
membranes, bradycardia, depression, impotence, constipation and diarrhoea, sleep disturbance, ﬂ  uid retention, headache, euphoria, 
and Raynaud’s phenomenon.
T oxic effects : a clonidine withdrawal syndrome may occur on

T oxic effects : a clonidine withdrawal syndrome may occur on 
abrupt withdrawal or non-compliance; paralytic ileus, psychotic features, or depression can also occur; coma or severe sedation can occur on acute overdose.
Indications : rapid opiate withdrawal and opiate antagonist-
assisted withdrawal; it is also used as adjunct for alcohol, benzodi-azepine, and nicotine withdrawal.
Contraindications:  low baseline blood pressure, disorders of 
cardiac pacemaker activity and conduction, cardiovascular and cerebrovascular disease, and porphyria; caution is necessary in renal and hepatic impairment, peripheral vascular disease, and where there is a history of depression or psychosis.
Interactions : combinations with sedative drugs; phenothiazines 
may increase hypotension. Tricyclic antidepressants may block its effects.
Effects of withdrawal : an increase in sympathetic activity with 
symptoms mimicking the opiate withdrawal syndrome may occur

symptoms mimicking the opiate withdrawal syndrome may occur 
18 to 72 h after the last dose on abrupt termination. Blood pressure rebound is rare when used for less than 1 month. The effects are minimized by gradual withdrawal.
Dosage and administration : expertise is needed to monitor 
cardiovascular signs and adjust dose during a clonidine detoxiﬁ  ca-
tion over 1 to 3 weeks. Start clonidine after discontinuation of the opioid. Following a test dose, 0.1 mg tablets are given four to six times daily building up to 2 mg daily over a few days in inpatientsbut half this dose in outpatients. Patches applied once weekly and supplemented by tablets if withdrawal symptoms occur. Frequent monitoring for hypotension and bradycardia is needed.
Lofexidine(13–15)  (BritLofex ®)
Lofexidine is an analogue of clonidine, but easier to use because there is less hypotension and sedation.

Pharmacology : as for clonidine; differences occur possibly 
because it is more potent at the A subtype of α
2-adrenoceptors.
Types of compounds available : 0.2-mg oral tablets; these 
are licensed in the United Kingdom only.
Pharmacokinetics :tmax 3 h; half-life of 15 h.
Side-effects : these are the same as for clonidine, but with 
markedly less hypotension and other side-effects.
T oxic effects : as for clonidine; it has little rebound effect on blood 
pressure, and no psychiatric complications or misuse has been reported.
Indications and contraindications : as for clonidine.
Interactions : as for clonidine.
Effects of withdrawal : as for clonidine, but less rebound.
Dosage and administration : treat for 1 to 3 weeks; dose may be

Dosage and administration : treat for 1 to 3 weeks; dose may be 
started before opiate is stopped; on day 1, give 0.8 mg in divided doses, and build up by 0.4 to 0.8 mg daily. Aim for a minimum of 1.6 mg daily in four divided doses, increasing to a maximum daily dose of 2.4 mg. Plan for a peak in the dose when the peak of withdrawal 
symptoms are expected. Blood pressure should be monitored 2 h 
after the initial dose, and daily as the dose is increasing. After peak opiate withdrawal lofexidine should be withdrawn gradually over at least 2–4 days. The dose should be reduced by 0.2–0.4 mg daily.6.2.8 drugs used in the treatment of the addictions

SECTION 6  treatment methods in psychiatry 1246
Acamprosate (calcium 
acetylhomotaurinate)(16,17)  (Campral EC ®)
Acamprosate is a non-aversive agent used to maintain abstinence 
in alcohol-dependent patients during the most vulnerable period following detoxiﬁ  cation, which may work as an anticraving agent.
Pharmacology : this is not fully understood. It affects the 
brain’s γ-aminobutyric acid (inhibitory) and glutamate (excitatory) 
systems.
Types of compounds available : oral enteric-coated tablets 
containing 333 mg acamprosate.
max 5 h; half-life 21 h; steady state after 
7 days.
Side-effects : there are a range of dose-related side-effects which 
are mainly mild and transient, including diarrhoea and other gastrointestinal effects, pins and needles in the limbs, skin pruritus, confusion, and sexual effects. Transient reductions in blood pressure occur in those with alcohol-induced hepatic cirrhosis.

T oxic effects : hypercalcaemia is a theoretical possibility following 
overdose.
Indications : maintenance of abstinence following alcohol detox-
iﬁ cation; it is suitable for use in those with liver dysfunction.
Contraindications : renal impairment and severe hepatic failure.
Interactions : concomitant food decreases bioavailability.
Dosage and administration : begin treatment as soon as possible 
after detoxiﬁ  cation, and continue for 1 year. Four tablets a day 
(2–1–1) with meals if body weight is less than 60 kg, but six tablets a day (2–2–2) if over 60 kg. The drug should be continued during alcohol relapses.
Disulﬁ  ram(18–20)  (Antabuse ®)
An unpleasant disulﬁ  ram-ethanol reaction occurs when alcohol is 
consumed, acting as a deterrent or punishment if drinking occurs. Disulﬁ  ram is used under specialist supervision during periods of 
vulnerability to relapse.
Pharmacology : disulfiram is an aldehyde dehydrogenase

Pharmacology : disulfiram is an aldehyde dehydrogenase 
inhibitor leading to the accumulation of acetaldehyde after ethanol consumption.
Types of compounds available : 200-mg oral tablets.
Pharmacokinetics : inhibition of alcohol dehydrogenase develops 
slowly over 12 to 24 h and peaks at 48 h.
Side-effects : relatively non-toxic on its own, but may cause 
drowsiness, fatigue, halitosis, nausea, vomiting, and a decrease in libido. With alcohol, disulﬁ  ram causes nausea, vertigo, anxiety, 
blurred vision, hypotension, chest pain, palpitations, tachycardia, 
facial ﬂ  ushing, and throbbing headache. Symptoms can last 3 to 
4 days, but may persist for 1 week. Symptoms may occur even with small amounts of alcohol, but 25 to 50 per cent of patients experience little or no reaction at standard doses.
T oxic effects : the disulﬁ  ram-ethanol reaction may be very severe

T oxic effects : the disulﬁ  ram-ethanol reaction may be very severe 
with respiratory depression, cardiovascular collapse, cardiac arrhythmias, coma, cerebral oedema, hemiplegia, convulsions, and death. Chronic treatment and overdose may cause high blood pressure, hepatotoxicity, and neuropsychiatric complications.
Indications : it is used as a deterrent to the use of alcohol and 
maintenance of abstinence, especially if there is high motivation and good compliance in the patient.Contraindications : cardiac failure, cardiovascular or cerebro-
vascular disease, hypertension, peripheral neuropathy, psychosis, severe personality disorder, suicide risk, pregnancy, and breast feeding. It should be used with caution in hypertension, diabetes mellitus, epilepsy, impaired hepatic or renal function, respiratory disorders, cerebral damage, and hypothyroidism, as it may exacer-bate these conditions. Caution should be exercised in the elderly.

Interactions : caution with phenytoin, diazepam, chlordiazepoxide, 
theophylline, warfarin, and caffeine metabolism; acute psychosis or confusional state may occur with metronidazole. Concurrent tricyclic antidepressants may exacerbate the disulﬁ  ram-ethanol 
reaction and cause a toxic confusional state.
Effects of withdrawal : none but restoration of alcohol dehydro-
genase depends on de novo  enzyme synthesis which occurs over 6 
or more days.
Dosage and administration : after 24 h without alcohol, give

Dosage and administration : after 24 h without alcohol, give 
800 mg as a single dose on day 1, then reduce dose over 5 days from 100 to 200 mg daily. Effectiveness is dose related. Blood pressure should be monitored regularly if the patient is taking over 500 mg/day. Compliance is improved with monitoring (carbon disulphide breath test) and supervision. Patients should be warned not to ingest any alcohol, including alcohol in food, liquid medicines, and even toiletries. An alcohol challenge test may be done in specialist centres. The patient should be reviewed every 6 months at a minimum. Alcohol should be avoided for at least 1 week on termi-nating disulﬁ  ram.
Clomethiazole (edisylate)(21) (Heminevrin ®)
Clomethiazole (previously known as chlormethiazole) is a seda-
tive-hypnotic-anxiolytic which also inhibits the metabolism of alcohol resulting in a more gradual elimination of alcohol from the body.

Pharmacology : it is an agonist at the picrotoxin/barbiturate site 
of the GABA-A receptor, a glutamate antagonist, and an inhibitor of alcohol dehydrogenase.
Types of compounds available : oral and parenteral forms.
max 1 h (oral dosing); plasma half-life is 4 h 
but is double this in elderly people.
Side-effects : conjunctival irritation, nasal congestion, tingling 
in the nose, headaches, and reversible elevation of liver function tests.
T oxic effects : respiratory depression, sudden fall in blood pres-
sure, anaphylactic reactions, and death (often due to combination with alcohol).
Indications : acute alcohol withdrawal and delirium tremens 
in inpatients.
Contraindications : alcohol addicts who continue to drink,

Contraindications : alcohol addicts who continue to drink, 
pulmonary insufficiency, pregnancy, and lactation; caution is advised in renal impairment, severe liver damage, and cardiac and respiratory disease.
Interactions : alcohol and diazoxide may cause severe respiratory 
depression. Plasma levels are increased by cimetidine. It causes 
severe bradycardia with propranolol.
Effects of withdrawal : rebound insomnia and anxiety (as with 
other sedative drugs).
Dosage and administration : titrate using three or four daily 
doses according to patient response. Initially give 2 to 4 capsules, then 9 to 12 in divided doses over the next 24 h, 6 to 8 capsules on

1247
day 2, 4 to 6 on day 3, reducing it to 0 by day 6 to 9 in order to avoid 
dependency. Only use it by infusion where resuscitation facilities are available; initially give 3 to 7.5 ml/min, then reduce dosage to 0.5 to 1 ml/min (infusion no longer available in UK).
British National Formulary (BNF) www.bnf.org.
NIDA (National Institute on Drug Abuse) www.nida.nih.gov.
SAMHSA (Substance Abuse and mental health services administration). 
 1. Lingford-Hughes, A.R., Welch, S., and Nutt, D.J. (2004). Evidence-
based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology ,
18, 293–335.
 2. NICE. (2007). Methadone and buprenorphine for the management of 
opioid dependence. NICE technology appraisal guidance 114 . National 
Institute for Health and Clinical Excellence, London.

2. NICE. (2007). Methadone and buprenorphine for the management of 
 3. Clark, N., Lintzeris, N., Gijsbers, A., et al. (2002). LAAM maintenance 
vs methadone maintenance for heroin dependence. The Cochrane 
Database of Systematic Reviews , (2): CD002210.
 4. Law, F.D., Myles, J.S., Daglish, M.R.C., et al.  (2004). The clinical use 
of buprenorphine in opiate addiction: evidence and practice. Acta 
Neuropsychiatrica ,16, 246–74 (with erratum at 2004, 16, 326).
 5. Nutt, D.J. (1997). Receptor pharmacology of buprenorphine. Research 
and Clinical Forums ,19, 9–15.
 6. Krausz, M., Verthein, U., Degwitz, P ., et al.  (1998). Maintenance 
treatment of opiate addicts in Germany with medications containing codeine—results of a follow up study. Addiction ,93, 1161–7.
 7. Robertson, J.R., Raab, G.M., Bruce, M., et al.  (2006). Addressing

 7. Robertson, J.R., Raab, G.M., Bruce, M., et al.  (2006). Addressing 
the efﬁ  cacy of dihydrocodeine versus methadone as an alternative 
maintenance treatment for opiate dependence: a randomized controlled trial. Addiction ,101, 1752–9.
 8. Gonzalez, J.P . and Brogden, R.N. (1988). Naltrexone. A review of its 
pharmacodynamic and pharmacokinetic properties and therapeutic 
efﬁ cacy in the management of opioid dependence. Drugs ,35, 192–213.
 9. NICE. (2007). Naltrexone for the management of opioid dependence. 
NICE technology appraisal guidance 115 . National Institute for Health 
and Clinical Excellence, London.
10. Srisurapanont, M. and Jarusuraisin, N. (2005). Opioid antagonists for 
alcohol dependence. The Cochrane Database of Systematic Reviews , (1): 
CD001867.
11. Minozzi, S., Amato, L., Vecchi, S., et al.  (2006). Oral naltrexone

CD001867.
11. Minozzi, S., Amato, L., Vecchi, S., et al.  (2006). Oral naltrexone 
maintenance treatment for opioid dependence. The Cochrane Database 
of Systematic Reviews , (1): CD001333.
12. Handal, K.A., Schauben, J.L., and Salamone F.R. (1983). Naloxone. 
Annals of Emergency Medicine ,12, 438–45.
13. Gowing, L., Farrell, M., Ali, R., et al.  (2004). Alpha2 adrenergic agonists 
for the management of opioid withdrawal. The Cochrane Database of 
Systematic Reviews , (4): CD002024.
14. Kahn, A., Mumford, J.P ., Rogers, GA., et al. (1997). Double-blind study 
of lofexidine and clonidine in the detoxiﬁ  cation of opiate addicts in 
hospital. Drug and Alcohol Dependence ,44, 57–61.
15. Strang, J., Bearn, J., and Gossop, M. (1999). Lofexidine for opiate 
detoxiﬁ  cation: a review of recent randomised and open controlled 
trials. American Journal on Addictions ,8, 337–48.

16. Littleton, J. (1995). Acamprosate in alcohol dependence: how does it 
17. Wilde, M.I. and Wagstaff, A.J. (1997). Acamprosate: a review of its 
pharmacology and clinical potential in the management of alcohol dependence after detoxiﬁ  cation. Drugs ,53, 1038–53.18. Banys, P . (1988). The clinical use of disulﬁ  ram (Antabuse): a review. 
Journal of Psychoactive Drugs ,20, 243–60.
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Dependence ,27, 201–7.
6.2.9 Complementary medicines
Complementary medicines pose a particular challenge to medical 
practitioners who may feel that their patients need conventional treatment but often ﬁ  nd themselves out of their depth when 
patients ask about complementary therapies. Pharmacological options include herbal medicines, certain foods, and nutritional supplements such as vitamins and minerals. Physical treatments include acupuncture, massage, and osteopathy to name a few. Treatments, which purport to achieve their effects through changes in internal ‘energy ﬂ  ow’ include reiki, reﬂ  exology, healing, and therapeu-

tic touch, and also homeopathy and traditional Chinese acupunc-ture. All these treatments are either used alternatively, i.e. instead of, or complementary, i.e. in addition to, conventional medicine. In patients with mental health problems, depending on the deﬁ  nition 
and inclusion criteria, estimates of the prevalence of complemen-tary medicine use range from 8 per cent to 57 per cent. Depression and anxiety seem to be the most common indications.
(1)
Herbal remedies and supplements
Principles of treatment
Herbal remedies and supplements may come in many different forms and formulations. Since they are currently not subject to the same regulatory requirements as conventional medicines they can vary substantially in contents and dose even if they purport to con-tain the same ingredients. The pharmacological properties of an extract or a supplement may depend on many different factors (Table 6.2.9.1).
Condition-speciﬁ  c remedies
Cognitive enhancers

Cognitive enhancers are either used in the treatment of dementia 
to enhance mental performance or prevent cognitive decline in healthy people. One strategy aims at increasing choline availability, e.g. by inhibiting acetylcholine esterase. Alternative non-choliner-gic neuroprotective strategies have been postulated. These rely on antioxidants scavenging free radicals thereby reducing neurotoxic-ity or anti-coagulants and increasing cerebral blood flow.
(4)
Suggested herbal cognitive enhancers for which some positive trial evidence has been collated include ginkgo ( Ginkgo biloba ), panax 6.2.8 drugs used in the treatment of the addictions

SECTION 6  treatment methods in psychiatry 1248
ginseng ( Panax ginseng ), hydergine ( Claviceps purpurea ), sage 
(Salvia ofﬁ  cinalis ), and vitamin E. The potential side effects can 
be derived from the purported mechanisms of action. For example, remedies increasing the cerebral blood ﬂ  ow such as ginkgo may 
increase the risk of cerebral haemorrhage. Panax ginseng  has 
been associated with manic episodes and hydergine can lead to ergot poisoning unless dosed carefully. Some sage species can lower the seizure threshold. Others contain camphor, which can be toxic in high doses.
(2) Also, evidence is emerging that taking vitamin E 
above the recommended level may increase all-cause mortality.(5)Anxiolytics and sedatives

Drugs considered to be either anxiolytics or sedatives essentially have the same underlying mechanisms of action. The stronger an agent the more sedating it will be, leading to coma in extreme cases. Four mechanisms of action have been implicated; binding to γ-aminobutyric acid (GABA) receptors leading to hyperpolariza-
tion of the cell membrane through increased inﬂ  ux of chlorine 
anions; inhibition of excitatory amino acids (EAA) thereby also impairing the ability to form new memories; sodium channel blockade, reducing depolarization of the cell membrane; and cal-cium channel blockade, reducing the release of neurotransmitters into the synaptic cleft.
(4) The most commonly used CAMs for anx-
iolysis and sedation, such as valerian ( Valeriana ofﬁ  cinalis ), passion 
ﬂ ower ( Passiﬂ  ora incarnata) , kava ( Piper methysticum ), and German

ﬂ ower ( Passiﬂ  ora incarnata) , kava ( Piper methysticum ), and German 
chamomile ( Matricaria recutita ) are GABAergic. Lemon balm 
(Melissa ofﬁ  cinalis ) has cholinergic and GABAergic properties. For 
other plant remedies, including hops ( Humulus lupulus ), oats 
(Avena sativa ), lavender ( Lavendula angustifolia ), and starﬂ  ower 
also known as borage ( Borago ofﬁ  cinalis ), the actual mechanism of 
action remains unknown. Melatonin regulates the circadian rhythm and also has some GABAergic properties although trial evidence remains inconclusive. Some of these remedies can potentially have serious side effects. For instance, kava extracts have been associated with signiﬁ  cant and potentially fatal hepatotoxicity. Starﬂ  ower con-
tains γ-linolenic acid that may lower the seizure threshold. Some

tains γ-linolenic acid that may lower the seizure threshold. Some 
passion ﬂ  ower extracts may contain cyanide components. As expect-
ed, all remedies in this class can lead to drowsiness when taken in high doses and can potentiate the effect of synthetic sedatives.
Antidepressants and mood stabilizers
Most complementary antidepressants are thought to work through 
serotonergic and noradrenergic pathways. The most robust clinical data are available for St John’s wort ( Hypericum perforatum ), 
having been extensively reviewed in meta-analyses.
(1) Hyperforin, 
inhibiting the reuptake of monoamines, is thought to be the most likely active component. Supplements, such as S-adenosylmethio-
nine (SAMe), folic acid, l-tryptophan, and 5-hydroxytryptophan

nine (SAMe), folic acid, l-tryptophan, and 5-hydroxytryptophan 
are components or co-factors in the serotonin synthesis. For SAMe, equivalence to tricyclic antidepressants has been demonstrated. However, SAMe is very expensive and a suitable oral formulation may be difﬁ  cult to obtain. Selenium has also been suggested but the 
mechanism of action, albeit still unclear, seems to be different. Its antioxidant properties may reduce nerve cell damage. Selenium 
also facilitates conversion from thyroxin (T4) to thyronine (T3), 
and T3 substitution is one possible augmentation strategy for antidepressants. As for lithium, the therapeutic index is narrow. Omega-3 fatty acids are known to stabilize membranes and to facilitate monoaminergic, serotonergic, and cholinergic neuro-
transmission. The currently available evidence supports the use

transmission. The currently available evidence supports the use 
of eicosapentaeonic acid on its own or in combination with doco-sahexaonic acid as adjunctive treatment.
(6) Serotonergic remedies 
should not be combined with each other or with conventional anti-depressants because of the increased risk of serotonin syndrome. Equally, herbal antidepressants may induce mania in vulnerable patients although current evidence relies on case reports only. Finally l-tryptophan and 5-hydroxytryptophan should be avoided 
until the associated risk of eosinophilic myalgic syndrome is fully explained.Table 6.2.9 .1 Determinants of pharmacological properties of 
complementary medicines
Factor Problem Example
Material 
productionQuality may depend 
on plant material used, 
time of harvesting, 
geographical location, or other environmental 
factorsSt John’s wort extracts prepared 
from the ﬂ  owers are more potent 
than extracts prepared from the 
leaves
Extraction 
methodDetermines remedy

leaves
methodDetermines remedy 
compositionAlcoholic valerian extracts may 
be safer than aqueous extracts such as teas because harmful 
volatile substances (valepotriates) 
are eliminated more easily. The resulting extracts may be less 
potent though, since valepotriates 
have GABAergic properties.
(2) 
Conversely, aqueous kava extracts 
may be safer than alcoholic 
extracts because liver protective substances such as glutathione 
are retained
Standardization Difﬁ  cult to achieve 
if active ingredient is unknownSt John’s wort is based on the 
extract traditionally standardized on hypericin, a photosensitive 
red pigment. However, 
current evidence suggests that 
standardization should be based 
on hyperforin, which inhibits the reuptake of monoamines
(1)
Dosing Depends on

(1)
Dosing Depends on 
standardization300 mg of St John’s wort extract 
standardized on 0.5% or 5% 
hyperforin most likely have 
different pharmacodynamic effects
Contamination Increased and 
sometimes unexpected 
toxicityContamination with e.g. fertilizer 
residuals or heavy metals. 
Association of eosinophilicmyalgic 
syndrome and some 
5-hydroxy-tryptophan products may be at least in part due to 
contamination of some batches
Adulteration May lead to serious 
side effects and drug interactions falsely 
ascribed to the 
remedy per seAdulterants include steroids, 
NSAIDs, anticonvulsants, benzodiazepines, hypoglycemic 
agents, erectogenic agents, and 
warfarin
(3)

1249
Remedies for psychosis
Rauwolﬁ  a (Rauvolﬁ  a serpentina ) extracts were traditionally used 
before synthetic antipsychotics became widely available. Several alkaloid derivatives including reserpine were introduced in the 1950s. They block vesicular storage of monoamines so that the presence of monoamines in the cytoplasm is prolonged, enabling them to be more easily degraded by monoamine oxidases. In con-sequence, the amount of neurotransmitter available on depolariza-tion of the cell membrane is reduced.
(4) On the one hand, this may 
lead to a reduction of dopamine and the resolution of psychotic symptoms. On the other hand, less serotonin and noradrenaline will be available, which explains why drugs such as reserpine may precipitate depression. An alternative strategy is the augmentation of antipsychotic treatment with omega-3-fatty acids, but the results of clinical trials remain inconclusive and larger trials will be needed to clarify effectiveness.
(6,7)

(6,7)
Remedies for movement disorders
Attempts have been made to treat tardive dyskinesia with antioxi-dants. This approach relies on the assumption that tardive dyskine-sia is not only due to dopamine receptor super-sensitivity but is also related to oxidative tissue damage induced by antipsychotics. Clinical trials suggest that vitamin E may prevent the progression of tardive dyskinesia. One trial found actual improvement. However, the beneﬁ  ts have to be offset against taking vitamin E 
long-term, particularly when higher than recommended daily doses are used.
(5) A far more powerful antioxidant than vitamin E 
is melatonin attenuating dopaminergic activity in the striatum as well as hypothalamic dopamine release.
(8)
Remedies for the treatment of addiction
Only few plants have been identiﬁ  ed as having the potential to 
counter addiction. Such may be ibogaine, derived from the West African shrub Tabernanthe iboga . It has hallucinogenic properties,

counter addiction. Such may be ibogaine, derived from the West African shrub Tabernanthe iboga . It has hallucinogenic properties, 
and has been used to counter nicotine, cocaine, and opiate addic-tion. It causes dose-dependent CNS stimulation ranging from mild excitation and euphoria to visual and auditory hallucinations. The therapeutic value of ibogaine is limited since it is highly neuro-toxic and can cause irreversible cerebellar damage. A synthetic derivative with similar reported effects, but without cerebellar toxicity is 18-methoxycoronaridine (18-MC).
(4) Between 1990 and 
2006, twelve deaths after ibogaine use were reported. More deaths may have occurred but may not have been reported due to the ‘underground nature of ibogaine treatment’ . Passion ﬂ  ower and 
valerian, by virtue of their GABAergic properties, may ameliorate withdrawal symptoms. Kudzu, Japanese arrowroot ( Pueraria

valerian, by virtue of their GABAergic properties, may ameliorate withdrawal symptoms. Kudzu, Japanese arrowroot ( Pueraria 
lobata ), has traditionally been used for the treatment of alcohol 
hangover. The active ingredient, puerarin, counteracts the anxio-genic effects associated with alcohol withdrawal.
(9)
Examples of remedies commonly used for chronic 
somatic conditions
Many different remedies are available for somatic conditions. Their 
use may be problematic in chronic conditions such as cancer or HIV where the therapeutic margin of conventional medicines is narrow.
(10) For example, echinacea ( Echinacea purpurea ) is used to 
boost immune system. This may be detrimental where immunosu-pression is desired since echinacea may potentially stimulate the growth of malignant or infectious cell lines. Patients with breast 
cancer may often resort to phytoestrogens such as soy ( Glycine 
max), wild yam ( Dioscorea alata ), or liquorice ( Glyccyrhiza glabra )

to reverse the effects of antiestrogenic therapies such as tamoxifen. Phytoestrogens, however, can theoretically stimulate breast cancer cells and thus should be advised against in this patient group. Liquorice is a popular ingredient of many traditional Chinese medicines and may cause hypokalemia if used excessively. Evening primrose ( Oenothera biennis ) oil is a popular remedy for premen-
strual syndrome and mastalgia. Like starﬂ  ower it contains γ-linolenic
acid and may lower the seizure threshold or reduce the efﬁ  cacy of 
antiepileptic drugs.
Determining interactions between complementary and conven-tional medicines can be extremely difﬁ  cult. In the ﬁ  rst instance, the

Determining interactions between complementary and conven-tional medicines can be extremely difﬁ  cult. In the ﬁ  rst instance, the 
clinician must be prepared to consider such a possibility and take a corresponding history. As often, association does not prove causality. Drug interactions can be distinguished into pharmacodynamic and pharmacokinetic interactions. Pharmacodynamic interactions occur when remedies act as agonists, antagonists or inverse agonists 
to conventional medicines. Additive toxicity, e.g. hepatotoxicity due to pyrrolizidine alkaloids, or increase of coagulability due to coumarinic constituents may also be of concern. Pharmacokinetic interactions include interactions with the cytochrome microsomal enzyme system (CYP) or membrane transporter proteins expressed through the ABC cassette genes (Table 6.2.9.2).
(1, 2, 11, 12)
The CYP system

The pharmacokinetics of most anticancer drugs is highly variable and may be genetically determined. For instance, the oxidative metabolism depends on the CYP system. The effects of CYP inducers and inhibitors are essentially differential depending on whether metabolites are more or less active (Table 6.2.9.2). If metabolites 
are less active than the original agent, CYP inhibitors increase 
whereas inducers reduce therapeutic effectiveness. Conversely, if 
metabolites are more active than the original agent, CYP inhibitors 
reduce whereas as inducers increase therapeutic effectiveness. Often 
such interactions have only been studied in vitro  and it remains 
unclear whether they translate into tangible clinical effects.
(11,12)

(11,12)
In clinical practice, it is often possible to monitor combination of medicines more closely or to adjust the doses of conventional drugs in the required direction rather than to advise discontinuation of complementary remedies. Interactions with CYP 3A4 are of particular concern, since this enzyme metabolizes up to 60% of all clinically used drugs including HIV protease inhibitors, HIV non-nucleoside reverse transcriptase inhibitors, warfarin, ciclospo-rin, oral contraceptives, digoxin, theophylline, anticonvulsants, and various psychoactive drugs.
(13)
ABC transporters
The ABC cassette genes represent proteins binding to ATP and use this energy to drive various molecules through cell membranes. The transport is mostly unidirectional. The ABC genes have been mainly explored for their capacity to cause multi-drug resistance in cancer chemotherapy.

(12) Thus remedies exerting such effects may 
be of particular interests to the liaison psychiatrist. The most commonly known transporter is p-glycoprotein involved in the 6.2.9 complementary medicines

SECTION 6  treatment methods in psychiatry 1250
transport of many psychotropic drugs through the blood brain 
barrier. St John’s wort, valerian, and panax ginseng are remedies shown to change p-glycoprotein activity (Table 6.2.9.2).
(11,12)
However, whether such effects are sufﬁ  ciently powerful to affect 
conventional treatments remains unclear.(14)
At present, the evidence base for the use of psychotropic comple-mentary medicines is extremely limited. Due to the large variability of formulations it can be extremely difﬁ  cult to conduct clinical 
trials with replicable results even if a candidate plant has been identiﬁ  ed. Pooling results of existing trials in meta-analyses may 
be unhelpful if the trials are too small or heterogenous or if the analysis is not adjusted for the extract types used. Equally, system-atic pharmacovigilance is difﬁ  cult to implement in the absence of a 
regulatory framework.
Clinicians need to be aware that patients may use complementa-

ry therapies regardless of the evidence available and should inquire about such forms of self-medication. Pattern of use may vary with cultural background and health beliefs. Given the com-plex pattern of potential interactions, conventional health care 
professionals should not be afraid to discuss complementary use 
with their patients. For instance, complementary medicines should be considered a potential cause when the clinical presentation, the treatment result, adverse effects, or even diagnostic investigations 
are unusual or unexpected. Equally, patients should be encouraged

are unusual or unexpected. Equally, patients should be encouraged 
to disclose information about complementary medicines to health care professionals. On the one hand, discussions need to be con-ducted sensitively in order to avoid alienating patients who may feel that they have not been taken seriously or have been criticized for using complementary medicines. On the other hand, uncritical encouragement of potentially harmful or inappropriate use of complementary medicines may possibly lead to litigation.(15) In most cases, remedies may not have to be discontinued if conven-tional treatments are closely monitored and adjusted. A construc-tive discussion about complementary medicines may potentially be a gateway towards enhancing compliance with conventional treatments.
Memorial Sloan-Kettering Cancer Center: Cancer Information: 
Integrative Medicine: www.mskcc.org. Keyword: herbs.
National Centre for Complementary Alternative Medicines / National

National Centre for Complementary Alternative Medicines / National 
Institute of Health: http://nccam.nih.gov.
Royal Botanic Gardens, Kew: Education: Resources: Information 
Sheets: www.rbgkew.org.uk/ksheets/.
Royal College of Psychiatrists: Mental Health Information: Therapies: 
Complementary and Alternative Medicines 1 & 2: www.rcpsych.ac.uk/mentalhealthinformation/therapies.aspx.Table 6.2.9 .2 Examples of potential drug interactions of commonly used psychotropic remedies
Remedy Pharmacodynamic Pharmacokinetic
Ginkgo Antithrombolytic agents 1A1, 1A2, 2B1/2, 2C9, 2C19 *, 3A1, 3A4 inhibition
Panax ginseng Insulin and oral hypoglycaemics, antithrombolytic agents, MAOIs 
(phenelzine), loop diuretics1A1, 1A2, 1B1, 2C9, 2C19, 2D6 , 2E1 inhibition3A4 
inconclusive; p-glycoprotein inhibition

Hydergine Serotonergic antidepressants, choline-esterase inhibitorsVitamin E Anticoagulants and antiplatelet drugs; prevention of nitrate tolerance 
possible; ↑ effect of sildenaﬁ  l and related phophodiesterase-5 inhibitors 
possible; ↓ effect of chemotherapies relying on oxidative stressCYP 3A11 induction
Valerian ↑ Effect of sedatives CYP 3A4  and p-glycoprotein inhibition
Passion ﬂ  ower Anticoagulants, ↑ effect of sedatives CYP 3A4 inhibition
Kava ↓ Effect of levodopa Potentiation of liver toxicity of other drugs
CYP 1A2, 2C9, 2C19, 2D6, 3A4 and 4A9/11 inhibition
Melatonin Anticoagulants, ↑ effect of sedatives;  ↓ effect of chemotherapies relying 
on oxidative stress
St John’s wort Serotonergic antidepressants CYP 3A4, 1A2, 2C9, 3A4 and 2E1 induction:, 
p-glycoprotein induction

Omega 3 fatty acids ↑ Effect of warfarin, aspirin and non- steroidal anti- inﬂ  ammatory drugs CYP 3A4 and p-glycoprotein inhibition
Rauwolﬁ  a ↑ Effect of anti- psychotics and barbiturates; ↓ effect of levodopa; severe 
bradycardia with digitalis glycosides; hypertension in combination with 
sympathomimetics
Iboga Cholinergic and anticholinergic drugsEchinacea ↓ Effect of immunosuppressants CYP 2A1 , 2C9, and 3A4 inhibition, CYP 3A4 induction 
also possible depending on extract
Evening primrose oil Other drugs reducing seizure threshold, anticoagulants 1A2, 2C9, 2C19, 2D6, 3A4 inhibition
*Bold font: In vivo  evidence available.

1251
The Prince of Wales Foundation for Integrated Health: http://
www.ﬁ  h.org. uk/.
 1. Werneke, U., Turner, T., and Priebe, S. (2006). Complementary 
alternative medicine in psychiatry: a review of effectiveness and safety. The British Journal of Psychiatry ,188, 109–21.
 2. Natural Medicines Comprehensive Database. (2007). Keyword: 
product search. www.naturalmedicines.com.
 3. Ernst, E. (2002). Adulteration of Chinese herbal medicines with 
synthetic drugs: a systematic review . Journal of Internal Medicine, 
252, 107–13 .
 4. Spinella, M. (2001). The psychopharmacology of herbal medicine .
MIT Press, Cambridge.
 5. Food Standards Agency. Expert Group on Vitamins and Minerals. 
(2003). Safe upper levels for vitamins and minerals . www.
foodstandards.gov.uk.
 6. Freeman, M.P ., Hibbelen, J.R., Wisner, L.K., et al. (2006). Omega-
3 fatty acids: evidence base for treatment and future research in psychiatry. The Journal of Clinical Psychiatry ,67, 1954–67.

6. Freeman, M.P ., Hibbelen, J.R., Wisner, L.K., et al. (2006). Omega-
 7. Joy, C.B., Mumby-Croft, R., and Joy, L.A. (2003). Polyunsaturated 
fatty acid supplementation for schizophrenia  (Cochrane review ). In The
Cochrane Library, Issue 4, John Wiley & Sons, Ltd., Chichester, UK.
 8. Lohr, J.B., Kuczenski, R., and Niculescu, A.B. (2003). Oxidative 
mechanisms and tardive dyskinesia. CNS Drugs ,17, 47–62.
 9. Overstreet, D.H., Keung, W.M., Rezvani, A.H.,  et al.  (2003). Herbal 
remedies for alcoholism: promises and possible pitfalls. Alcoholism: 
Clinical and Experimental Research ,27, 177–85 .
10. Labriola, D. and Livingston, R. (1999). Possible interactions 
between dietary antioxidants and chemotherapy. Oncology
(Williston Park ), 13, 1003–8.
11. Sparreboom, A., Cox, M.C., Acharya, M.R., et al.  (2004). Herbal

11. Sparreboom, A., Cox, M.C., Acharya, M.R., et al.  (2004). Herbal 
remedies in the United States: potential adverse interactions with anticancer agents. Journal of Clinical Oncology, 22, 2489–503 .
12. Sparreboom, A., Danesi, R., Ando, Y., et al.  (2003). 
Pharmacogenomics of ABC transporters and its role in cancer chemotherapy. Drug Resistance Updates ,6, 71–84.
13. Committee of Safety in Medicine & Medicines Control Agency. 
(2000). Reminder: St John’s wort ( Hypericum perforatum )
interactions. Current Problems in Pharmacovigilance ,26, 6–7.
14. Morris, M.E. and Zhang, S. (2006). Flavonoid-drug interactions: 
effects of ﬂ  avonoids on ABC transporters. Life Sciences ,78, 2116–30.
15. Cohen, M.H. and Eisenberg, D.M. (2002). Potential physician 
malpractice liability associated with complementary and integrative medicinal therapies. Annals of Internal Medicine ,136, 596–603.

6.2.10 Non-pharmacological 
somatic treatments
Contents
Max Fink
Keith Matthews and David Christmas6.2.10.1 Electroconvulsive therapy
Max Fink
Convulsive therapy (ECT or electroshock) is an effective treatment

Max Fink
Convulsive therapy (ECT or electroshock) is an effective treatment 
for those with severe and persistent emotional disorders. It is safe for patients of all ages, for those with debilitating systemic illnesses and during pregnancy. It relieves symptoms in a briefer time than do psychotropic drugs. T o achieve remission, treatments are usually given three times a week for two to seven weeks. T o sustain recovery, treatments are continued either weekly or biweekly for several months. The overall duration of the treatment course is similar to that of the psychotropic medications frequently used for the same conditions.
The treatment is severely stigmatized and its use is discouraged, 
even interdicted, in the belief that the electricity or the seizures irreversibly damage the brain.
(1–5) Few physicians are tutored in its

(1–5) Few physicians are tutored in its 
use and facilities are limited making ECT unavailable to many who would beneﬁ  t. The ease in the use of psychotropic medications, 
and neither greater efﬁ  cacy nor greater safety, encourages their 
preferential use as ECT is relegated to the ‘last resort.’ In countries where psychotropic medications are expensive, ECT is prescribed, but the expense for anesthetics limits its use to its unmodiﬁ  ed 
form.
Despite these hurdles of stigma, expense and lack of training, its 
use has persisted for more than 70 years. Indeed, its use is increas-ing. Whole societies where it was interdicted at the end of the 20
th century, as in the Netherlands, Germany, Austria, Italy, and 
Japan, interest and usage has increased, texts have been written or translated, and local psychiatric societies formed to encourage its use.
(4–6)
Origins

(4–6)
Origins
At the turn of the century when malarial fevers were used to treat patients with neurosyphilis, it was deemed possible to treat one illness by developing another. Reports that patients with dementia praecox were relieved of their psychosis after suffering convulsions supported a concept of an antagonism between epilepsy and psy-chosis. An explanation was seen in the reports that the concentra-tions of brain glial cells in patients with dementia praecox were low and in those with epilepsy were high.
(7) Was it possible that the 
root of schizophrenia lay in the paucity of glia and would their increase relieve the illness?
After testing ways to induce a grand mal seizure in animals,

After testing ways to induce a grand mal seizure in animals, 
Ladislas Meduna, a Hungarian neuropathologist and psychiatrist, on January 24, 1934, injected camphor-in-oil into a man with the catatonic form of schizophrenia. The patient seized and recovered without incident. Following the model of malarial fever therapy, Meduna repeated the injections every three days, and after the ﬁ  fth 
seizure, the patient, for the ﬁ  rst time in four years, talked spontane-
ously and fed and cared for himself. After three additional treat-ments he was discharged home, returned to work, and was well when Meduna left Hungary in 1939.
(7)
Chemically induced seizures, either with camphor or pentylene-
tetrazol (Metrazol), were rapidly adopted worldwide as the treat-
ment for dementia praecox, but the treatments were painful and 6.2.10.1 electroconvulsive therapy

SECTION 6  treatment methods in psychiatry 1252
frightening, so alternative means were sought. In 1938, the Roman 
psychiatrists Ugo Cerletti and Luigi Bini demonstrated the ease of administration and the efﬁ  ciency of electrically induced seizures. 
Quickly, ‘electroconvulsive therapy’ (ECT, electroshock) became the commonest method of inducing seizures and is the standard induction today.
(4–5, 8)
For whom is ECT effective?
Established DSM diagnoses are usually cited as the indications for ECT. The diagnoses are imprecise, however, offering heterogeneous population samples. A syndromic view offers more homogeneous populations for treatment.
(9–11)
Deﬁ ned by DSM Classiﬁ  cation . The DSM deﬁ  ned conditions 
for which ECT is prescribed are cited in established texts(12–15)
(Table 6.2.10.1.1). The breadth of its clinical efﬁ  cacy across major 
DSM diagnostic classes is striking, reﬂ  ecting commonalities in the

DSM diagnostic classes is striking, reﬂ  ecting commonalities in the 
pathophysiology of different disorders. This experience challenges the concept that DSM classiﬁ  ed disorders are distinct biological 
abnormalities, and supports the 19
th century concept of a unitary 
psychosis.(16)
ECT is not useful for a patient with neurosis, situational malad-
justment, personality disorder (character pathology), or drug dependence. It is of limited beneﬁ  t for anyone with a lifelong history 
of mental and emotional dysfunction, unless the onset of the present illness is acute and well deﬁ  ned, or affective, psychotic, or catatonic 
features dominate the presentation
(12–15) (Table 6.2.10.1.2).
Deﬁ ned by syndrome. DSM-III and DSM-IV classify illnesses 
based on the check-off of symptoms modiﬁ  ed by duration criteria.

based on the check-off of symptoms modiﬁ  ed by duration criteria. 
The DSM criteria identify heterogeneous populations that do not support useful treatment algorithms or the search for biological roots of the illnesses. Clinical syndromes describe more homoge-neous populations, often substantiated by biological tests and/or a high speciﬁ  city of interventions. Melancholia, psychotic depres-
sion, catatonia, delirious mania, and acute schizophrenia are syn-dromes that are particularly responsive to ECT (Table 6.2.10.1.3). These syndromes are not readily identiﬁ  ed in the established clas-
siﬁ cation systems. Summary descriptions are offered here; the 
interested reader will ﬁ  nd more extensive descriptions in the cited 
literature.
(a) Depressive mood disorders

Convulsive therapy is most effective against mood disorders, depression and mania. Depressive mood disorders are dominated by sadness, hopelessness, fears, and thoughts that life is no longer worth-living. Variants are recognized, dominated by vegetative and motor abnormality (melancholia), by delusions (psychotic depression), by severe cognitive deﬁ  cit (pseudodementia), or by 
catatonia.
(14)
While all variants respond to induced seizures, some also respond 
to other speciﬁ  c treatments. Melancholic and pseudodementia 
patients respond to tricyclic antidepressants. Psychotic depressed 
patients require high doses of both antidepressant and antipsychotic medications.
(11) Anticonvulsant sedative drugs, the barbiturates 
and the benzodiazepines, are useful in catatonic patients.(9)
(i) Melancholia

Motor signs (retardation or agitation) and vegetative symptoms of inability to sleep, feeding, and weight loss are its features. Work, sex, and family are disregarded. Thoughts of suicide are prominent.
(10–11)Hypercortisolemia is characteristic of the syndrome.(17) Cortisol 
metabolism is inﬂ  uenced by hypothalamic, pituitary, and adrenal 
interactions. Melancholic patients exhibit elevated serum levels of cortisol, obtunded diurnal rhythmicity, and serum levels remain elevated despite an administered dose of dexamethasone. The abnormality is measurable by the dexamethasone suppression test (DST) or its variant, the dexamethasone/corticotrophin releasing factor test (Dex/CRH). Elevated cortisol levels normalize with treatment and become abnormal again with relapse. In the 1980s, the speciﬁ  city of the DST was considered poor for the major

depressions deﬁ  ned by DSM-III and the test was discarded. But the 
re-assessment of the literature and recent reports ﬁ  nd the test as Table 6.2.10.1.1  DSM deﬁ  ned clinical diagnoses in which ECT is 
effective
(11)
Major depressive disorder
 single episode [296.2x]**
 recurrent [296.3x]**
 mania [296.4x]**
 depressed [296.5x]** mixed type [296.6x]**
 not otherwise speciﬁ  ed [296.70]**
Atypical psychosis [298.90]
 catatonia [295.2x]
 schizophreniform [295.40] schizo-affective [295.70]
Catatonia
 Schizophrenia, catatonic type [295.2x]
 Catatonic disorder due to a medical condition [293.89]
 Malignant catatonia [293.89] Neuroleptic malignant syndrome [333.92]
Delirium
 Due to a general medical condition [293.0]
 Due to substance intoxication
* from Fink, 1999
** speciﬁ  er for psychosis
Table 6.2.10.1.2  DSM diagnoses in which ECT is ineffective11
Dementia and Amnestic Disorders [293.0, 290.xx, 294.xx]

Due to substance intoxication
Substance-related Disorders [303.xx, 291,x, 304.x, 292.x]Anxiety and Somatiform Disorders [300.xx]Factitious Disorders [300.xx]Dissociative Disorders [300.1x, 300.6]Sexual Dysfunctions [302.xx, 625.8, 608.89, 607.84, 608.89, 625.8]Sleep Disorders [307.xx, 780.xx]Impulse disorders [312.3x]Adjustment disorders [309.xx]Personality disorders [301.xx]

1253
both sensitive and speciﬁ  c for melancholic depression, where it has 
a positive predictive value.(11,18)
After an extensive review of the literature, Taylor and Fink (2006) 
concluded that classifying mood disorder patients as either melan-cholic or non-melancholic offered more homogeneous popula-tions with better outcomes with TCAs and ECT than did the DSM classiﬁ  cation of major depression and bipolar disorder.
(11) In their 
formulation, melancholia is a syndrome of depressive mood, with motor and vegetative abnormalities and with evidence of cortisol abnormality.
(ii) Delusional (psychotic) depression
Overwhelmed by feelings of helplessness, hopelessness, and worth-lessness, the patient believes others are watching or talking about him, reporting voices when no one is present. He imagines that events depicted on a television or movie screen apply directly to him. This form is labelled psychotic depression and is remarkably responsive to ECT.

In 1975, Glassman and his associates at Columbia University 
reported that only three of 13 delusional depressed patients (23 per cent) improved when they were treated with high doses of imipramine, while 14 of 21 non-delusional patients (66 per cent) improved under the same treatment.
(18) Nine of the 10 unimproved 
delusional patients responded well to ECT. These ﬁ  ndings have 
been repeatedly veriﬁ  ed.(11,12)
In a study of 437 depressed hospitalized patients treated with 
imipramine in doses of 200 to 350 mg/day for 25 days or longer, 
247 (57 per cent) were evaluated as re covered and we re disc harged.(19)
When the 190 unimproved patients were treated with bilateral 
ECT, 156 (72 per cent) were recovered. Most of the depressed patients who had not improved with imipramine were delusional as well as depressed.
Only a third of delusional depressed patients recover when 
treated with antidepressant drugs alone and half recover with antipsychotic drugs alone.

(11, 19–20) Two-thirds of those treated 
with ECT or with high doses of both antidepressant and antipsy-chotic drugs regain their health.
In a two-year study of late-life depression, 47 per cent of the 
delusional depressed patients treated with medication relapsed ear-lier and more often than the nondelusional depressed (15 per cent), indicating that delusional depression is particularly resistant to medication.
(21) It is, however, so amenable to ECT that it is consid-
ered a primary indication for its use.(11–14) But the condition is dif-
ﬁ cult to diagnose making inadequate treatment common. In a 
three-hospital research study of ECT and continuation medica-tions, only 2 of 52 delusional depressed patients had adequate courses of medication treatment before they were referred for ECT.

(22) The same failure was found in another multi-center study 
with only 5 of 106 patients failing adequate courses of treatment before referral to ECT.
(23)
Many reviews ﬁ  nd psychotic depression to have a more severe 
pathophysiology and just using the same treatments as for non-psychotic depression, even at much higher doses is not adequate.
(11,12)
Y et, bilateral ECT is remarkably effective. In a multi-site collabora-tive ECT study, of 253 patients with unipolar major depression, 77 were psychotic depressed. Their remission rate was 95 per cent compared to 83 per cent for the non-psychotic depressed, with the speed of response faster for the psychotic depressed patients.
(24, 25)
(iii) Pseudodementia (reversible dementia)

(24, 25)
Because the depressed patient ignores daily events, little of what happens to him is registered and memory is compromised. The condition is hardly distinguishable from Alzheimer’s dementia. The onset is usually more rapid and severe compared to the onset of a structural dementia, and patients often report a history of prior depressive episodes.
(11, 14)
Because the syndrome is not well known, patients are often sent 
to nursing home care. An example of a 58-year old woman who developed a reversible dementia and was not adequately treated for eight years is reported. Once the diagnosis was considered, antide-pressant treatment relieved the syndrome and returned the patient to a more normal family life.
(14)
(iv) Catatonia
When the patient is mute, sitting rigidly in a chair or lying motion-less on his bed, and unresponsive to questions and commands, he appears as in a stupor. The state is called catatonia  or depressive stupor .

Catatonia is seen among patients with many DSM diagnoses.
(9)
It is discussed in detail below.
(b) Manic mood disorders
A mood disorder dominated by grandiosity, expansiveness, feelings of increased power and energy, and excitement, can last for hours, days, weeks, or months. Even after it is relieved, it may recur or alternate or combine with episodes of depression. When the switch-es occur within one or a few days, the experience is labelled rapid 
cycling , a malignant form of the illness. Bipolar disorder  is the label 
applied to both mania and mixed forms of the illness.
(11, 26)
Disturbances in eating and sleeping, thinking, memory, and 
movement are features of mania. The patient does not sleep, eats poorly, loses weight, and concentrates thoughts poorly. Memory is impaired, often severely; he may be so disorganized as to appear demented and delirious. Melancholia, psychosis, pseudodementia, and catatonia variations are commonly seen.Table 6.2.10.1.3  ECT responsive syndromes

 Depression
  Melancholia
  Psychotic (Delusional) depression
 Mania
  Mixed States (mania, depression)  Rapid cycling mania
  Depressive phase of bipolar disorder
  Delirious mania
Psychosis
 Acute schizophrenia
 Postpartum psychosis
Catatonia
 Hypokinetic catatonia (Kahlbaum Syndrome) Excited catatonia (delirious mania, oneiroid state)
 Malignant catatonia (NMS, TSS)
Other
 Delirium Suicide risk
 Status epilepticus (SE < NCSE)
* from Fink, 1999.6.2.10.1 electroconvulsive therapy

SECTION 6  treatment methods in psychiatry 1254
Delirious mania is a striking form of mania. A normal person 
suddenly becomes excited, restless, and sleeps poorly, fears that neighbors are watching him, and is easily frightened. He may hide in the house or leave it abruptly, dressed inappropriately, some-times naked, and wander about the streets. His hallucinations are vivid, his thoughts disorganized. Confusion alternates with mut-ism, posturing, rigidity, and stereotyped repetitive movements. Physical exhaustion even to the point of death occurs.
(11, 27)
Before ECT, patients were sedated with opiates, bromides, or 
chloral and many died of poor care, inanition, and pneumonia. A 1994 summary of the reports of manic patients treated with ECT ﬁ nds 371/562 (66 per cent) remitted or showed marked clinical 
improvement.
(28) The introduction of chlorpromazine and other 
sedative drugs quickly replaced ECT for efﬁ  cacy and ease of use.

sedative drugs quickly replaced ECT for efﬁ  cacy and ease of use. 
But when chlorpromazine and other antipsychotic drugs were used in place of ECT, the doses often carried the risks of sudden death and neuroleptic malignant syndrome, as well as tardive dyskinesia and tardive dystonia.
(9)
Anticonvulsant drugs are now preferentially recommended, 
even though the evidence for their efﬁ  cacy is poor. Many authors 
encourage the use of lithium for immediate relief and for prophy-laxis. In 438 manic patients treated with ECT or lithium, 78 per cent of the ECT treated group showed marked improvement compared to 62 per cent of those treated with adequate doses of lithium and 56 per cent of those treated with inadequate doses.
(29) The group 
receiving neither ECT nor lithium fared least favourably with only 37 per cent improved.
No matter the array of medications and polypharmacy for mania, 
ECT is an effective alternative.

(c) Catatonia
Muscular rigidity, posturing, negativism, mutism, echolalia, echopraxia, and stereotyped mannerisms, the signs of catatonia, appear suddenly and immobilize patients.
(9) When the disorder is 
transient, it may be disregarded, but when it persists, it threatens life. Patients undergo forced feed ing and develop be dsores, muscular 
atrophy and pulmonary embolization. Repeated bladder catheteri-zations induce infections.
Catatonia is recognized in patients with affective illnesses, both 
depression and mania, in patients with systemic disorders, and in those with toxic brain states caused by hallucinogenic drugs. For decades, the prevailing belief was that each instance of catatonia represented schizophrenia. The major classiﬁ  cation systems in psy-

chiatry — DSM-III and IIIR of the American Psychiatric Association and the International Classiﬁ  cation of Diseases (ICD-IX, ICD-X) — 
assigned patients with catatonia to the diagnosis of schizophrenia, catatonic type. Few patients were treated with anticonvulsant 
sedatives or ECT, despite their known efﬁ  cacy, because neither was 
recommended for schizophrenia. This short-sighted view was somewhat corrected in the 1994 classification system of the American Psychiatric Association (DSM-IV), which recognized catatonia as secondary to systemic illness in the class of “ Catatonic
disorder due to . . . . (Indicate the General Medical Condition)[293.89]” .
(30) The experience that catatonia is not limited to patients 
with “schizophrenia” has led to the call for a separate category in DSM-V .
(9,31)
Catatonia is deﬁ  ned by the persistence of two or more character-
istic motor signs for more than 24 h in a patient with a mental disorder.

(9,31)
(9,31) Posturing and staring can be observed, but most signs require elicitation in the examination. The accepted motor 
signs and a formal examination are cited in catatonia rating scales.
(9) An intravenous challenge of lorazepam or amobarbital 
veriﬁ  es the diagnosis in more than 2/3 patients with catatonia, and 
a positive test response augurs well for high dose benzodiazepine 
therapy. When this treatment fails, ECT is effective, although the treatment schedule may require daily treatments.
Catatonia may be transitory or may persist for months or years. 
It appears in many guises.
(9, 32)  Prominent examples are malignant 
(pernicious) catatonia  (MC) with a high risk of death and the 
neuroleptic malignant syndrome  (NMS) that follows on the admin-
istration of neuroleptic drugs.
(i) Malignant catatonia

Descriptions of patients who develop an acute febrile delirium with excitement or stupor dot the literature. They often exhibit signs of catatonia. Vegetative dysregulation is often severe and death was a frequent feature before the introduction of ECT. Descriptions by Bell (1849), Stauder (1934), and Bond (1950) highlight the lethal nature of the syndrome. In 1952, Arnold and Stepan described patients in whom ECT rapidly relieved malignant catatonia, but to avoid mortality it had to be used within the ﬁ  rst ﬁ  ve days.
(9)
(ii) Neuroleptic malignant syndrome (NMS)
A toxic response to neuroleptic drugs evinced by fever, motor 
rigidity, negativism, mutism, and cardiovascular and respiratory instability is a toxic response to neuroleptic drugs. It is indistin-guishable from malignant catatonia.

(9, 32) It is an MC variant as the 
diagnostic criteria and effective treatments are the same as for MC. MC occurs with almost all neuroleptics, most commonly with the high-potency agents like haloperidol, ﬂ  uphenazine, and thiothixene, 
but also with atypical neuroleptics.
One hypothesis explains the syndrome as a consequence of an 
excessive reduction in the amount of brain dopamine. Those who believe this association prescribe the dopamine agonists bromoc-riptine or levodopa and relieve muscular rigidity by prescribing the muscle relaxant dantrolene. Neither of these treatments has proved effective and dantrolene use is associated with considerable toxicity.
(33)
These are best not used and patients are best treated with sedative anticonvulsants and ECT.
(iii) Toxic serotonin syndrome (TSS)

(33)
A toxic syndrome is occasionally described in association with the SSRI antidepressant drugs. TSS is similar to MC with prominent gastrointestinal symptoms. The diagnosis and treatment follows the protocol for MC.
(9)
(d) Psychosis
A severe impairment of thought characterized by delusions is a feature of many psychiatric conditions, notably manic delirium, psychotic depression, post partum depression, and toxic psychosis. It is broadly deﬁ  ned as a psychosis and diagnosed within the major 
class of psychoses as schizophrenia. In this class ECT is hardly considered. But when we consider the efﬁ  cacy of ECT in the psy-
chotic variants of the mood disorders, we appreciate that ECT is an effective treatment of psychosis.
(34)
Convulsive therapy was introduced for the treatment of demen-

(34)
tia praecox and was widely and quickly adopted. Comparisons with chlorpromazine found both treatments effective in acute and severe short-term illnesses, but neither was useful in chronic states. Chlorpromazine was favoured since its cost is considerably less and

1255
its image better. As more patients failed to respond to medications, 
however, a cadre of’medication resistant’ psychotic patients devel-oped. Families asked whether anything else could be done to better the patients’ lives. Friedel (1986) augmented a failed course of thi-othixene therapy with ECT, returning each of nine patients to community life. The finding was replicated in the successful augmentation in 8/9 psychotic patients.
(34)
Clozapine was described as a treatment for psychotic patients 
who had failed to respond to two different antipsychotics. As the experience with this treatment grew, clinicians were again faced with treatment failures and ECT augmentation was tried. A synergy for ECT and clozapine was described and offers an effective treat-ment for patients who have failed conventional antipsychotics and clozapine.
(34)
It is reasonable to consider ECT in the treatment of psychosis,

(34)
It is reasonable to consider ECT in the treatment of psychosis, 
whether in an affective illness or in schizophrenia. For the affective illnesses, ECT is used alone. In schizophrenia, ECT is effective alone or in augmenting neuroleptics.
(34)
(e) Delirium
Acutely ill psychotic patients often exhibit disturbances in 
consciousness and are confused. Delirium is common in toxic states, either drug induced (alcohol being the most common), or secondary to drug withdrawal, or associated with systemic illnesses. Delirium is a feature of acute manic states (e.g. delirious mania) and the confusional state described as oneirophrenia. With few resources to treat acute psychoses, ECT was applied with favourable results.
(14,35) The relief of delirium by ECT is 
an unrecognized effect that warrants consideration as an alternative to the risks of high potency neuroleptic drugs inducing NMS (MC).
(f) Neurological syndromes

ECT is well appreciated in catatonia, but it is also useful in status epilepticus (SE), non-convulsive status epilepticus (NCSE), and Parkinsonism.
(i) Status epilepticus
SE and NCSE are emergency conditions with high mortality rates. The pathophysiology is the persistence of seizures as biochemical inhibitory mechanisms fail to terminate a seizure.
(36) Despite ever 
larger doses of anticonvulsant medications, proceeding from lorazepam to phenytoin, phenobarbital, and general anesthesia with midazolam, propofol, or barbiturates, patients persist in SE and NCSE.
ECT is another effective intervention. During the course of 
electroconvulsive therapy, the seizure threshold rises, encouraging seizure termination. The ﬁ  rst report of the relief of intractable 
epilepsy by ECT in 1943 has been sporadically veriﬁ  ed.
(37)

(37)
An explanation for this application is physiologically interesting. 
The strength of a seizure can be judged by the immediate rise in serum prolactin after a sustained epileptic seizure. Within the hour after a seizure, the level of serum prolactin indicates whether the seizure is a cerebral grand mal event or a pseudoseizure. Serum prolactin levels do not rise in SE but remain normal. This suggests that the SE seizures are partial or incomplete and that they fail to stimulate an inhibitory termination process. But even in patients in SE, ECT elicits maximal seizures, making it a reason-able alternative to general anesthesia as a treatment for intractable seizures.(ii) Parkinsonism

In treating older depressed patients with concurrent Parkinsonism with ECT, motor and facial rigidity were also relieved. In Par kinsonism, 
brain dopamine levels are reduced, making dopamine agonists effective treatments. In ECT, brain and CSF levels of dopamine increase. Experiments in Parkinsonian patients without mood disorder found motor rigidity to be relieved.
(38) For those patients 
who are not relieved by conventional treatments, periodic ECT has been helpful. Continuation treatments, like continuation pharma-cotherapy, are necessary to sustain the beneﬁ  t.
(g) Suicide
All psychiatric disorders carry the risk of suicide. ECT reduces this 
drive. The impact of medications on suicide risk is not well deﬁ  ned 
but compared to ECT, the efficacy is less favourable.(6,11)
Comparisons of ECT and TCAs across different treatment eras ﬁ  nd

Comparisons of ECT and TCAs across different treatment eras ﬁ  nd 
the frequency of suicides decreased in the ECT era. A study of the psychiatric status of 519 patients six months after discharge from hospital treatment for depression found 0.8 per cent of the ECT treated patients had made a subsequent suicide attempt compared to 4.2 per cent for those rated as receiving adequate and 7 per cent of those receiving inadequate courses of antidepressant drugs. At the 6-month follow-up no suicides were reported in 34 women treated with ECT, but two suicides occurred in the 84 patients treated with antidepressants (2.4 per cent).
(39)
In a study of the expressed suicide intent (changes in Item 3 of

(39)
In a study of the expressed suicide intent (changes in Item 3 of 
the HAMD rating scale) in 148 patients treated with ECT, the base-line average score was 1.8. It reduced to 0.1 in 72 responders and to 0.9 in 76 non-responders. For the total sample, there was a greater decrease in the suicide item scores than in the overall HAMD scores.
(40)
In another study of 444 patients referred for ECT, 131 had high 
expressed suicide intent scores.(6) The scores dropped to zero in 
106 (80.9 per cent) with treatment, occurring in 38.2 per cent (50/131) after 3 ECT (one week), in 61.1 per cent (80/131) after 6 ECT (two weeks); and in 76.3 per cent (100/131) after nine ECT (three weeks).
ECT’s effect on the death rate in the mentally ill, particularly 
those with mood disorders, must be a major consideration in treat-ment recommendations.
When to consider ECT?  Psychotropic drugs and psychotherapy are

When to consider ECT?  Psychotropic drugs and psychotherapy are 
the ﬁ  rst treatments of the psychiatrically ill, with referral to ECT 
when these treatments fail. Since ECT is effective in medication treatment failures, would it not be wise to spare patients a pro-longed illness and risks of suicide by offering ECT as the initial treatment? ECT is indeed considered the ﬁ  rst treatment when there 
is a need for a rapid, deﬁ  nitive response, as in suicidal patients who 
require constant observation and restraint, in hyperactive patients 
who may be at risk of harm to themselves or others, in those with

who may be at risk of harm to themselves or others, in those with 
malignant disorders as malignant catatonia, neuroleptic malignant syndrome, or delirious mania, or in those whose lives are in jeop-ardy from systemic illness. It is also preferred in those patients who have had a prior illness that responded well to ECT or who have had a poor experience with medications.
(11–15)
How many failed trials of medications are reasonable before 
ECT is considered? For some patients, especially those whose prac-titioners are not knowledgeable about ECT, medication trials 6.2.10.1 electroconvulsive therapy

SECTION 6  treatment methods in psychiatry 1256
become interminable and ECT is considered only when the patient 
seeks care elsewhere. A reasonable guideline is derived from the experimental trials with clozapine, an agent with life-threatening risks.
(41) T o put patients at risk and yet obtain the possible beneﬁ  ts 
of clozapine, the researchers decided that patients should not be 
offered clozapine unless they had experienced two unsuccessful courses of neuroleptic treatment. A similar standard seems reason-able for recommending ECT. After patients have failed two different courses of medications at adequate doses and for adequate periods, ECT is to be considered.
Financial considerations affect the decision. If the patient is 
severely ill and has only a limited ability to pay for extended care, repeated unsuccessful medication trials are unwarranted. All practitioners should balance the cost of medication trials and the effective use of ECT.

Consideration of age.  ECT is an accepted treatment for adults. 
For decades, the attitudes of child and adolescent psychiatrists pre-cluded consideration of ECT for their patients except the most devastatingly ill. The acknowledged safety of ECT in adults relaxed prejudices against its use and led to more treatment trials. Once it became clear that the response of adolescents was similar to that of adults, the attitude changed and ECT is now an accepted treatment for adolescents with the same illnesses that are successfully treated in adults.
(42)
ECT is probably effective in similar conditions in children, but 
their expression of mood and psychotic disorders is different than in adults and difﬁ  cult to interpret. The published experience in the 
few children treated with ECT ﬁ  nds that conditions that respond in 
adults and adolescents also respond in children.
ECT is widely used in geriatric patients. Indeed, it is increasingly

ECT is widely used in geriatric patients. Indeed, it is increasingly 
called on when the side effects of medications become intolerable and when medication trials fail. The safety of modern ECT is such that even the frailest and systemically ill elderly can be safely treated with ECT. We acknowledge no absolute contraindication to ECT other than the lack of skill of the clinicians.
(11–15)
The treatment process
Consent . The referral of a patient to an ECT service starts the

(11–15)
Consent . The referral of a patient to an ECT service starts the 
treatment process. As in surgical treatment, the patient and family members are educated as to the risks and processes of the treatment course, and a signed voluntary consent, witnessed by a family member if possible, is obtained. In response to the turmoil of the 1970s when a draft for an unwelcome war led to widespread questioning of authority, attacks on ECT as a forced involuntary treatment led the profession to suggest procedures for informed voluntary consent. These procedures are well established.
(1, 2, 4, 12)
An explanation of why the treatment is recommended, speciﬁ  c 
anticipated beneﬁ  ts and risks, the names of the responsible physi-
cians, and a statement that the patient may, at any time, discontinue the treatment are elements of a valid consent.
(4,13,14)  Although vol-

untary consent is the basis for ECT in almost all Western countries, provisions for involuntary treatment for patients who may not be able to understand the severity of their illness nor the need for treatment is provided in state laws with courts authorizing treat-ment. In a few venues, surrogate consent by family members is accepted. Educational videotapes and books for laymen support the consent process.
(4, 12, 43)Procedures . Treatments are usually given in an equipped room 
with access to the in-patient wards. Increasingly, as more than half the treatments are given to out-patients, units are established with ready access to the community.
(12,13)
Prior to treatment, systemic medical examinations usually

(12,13)
Prior to treatment, systemic medical examinations usually 
advised for general anaesthesia are completed. These include com-plete blood count, electrocardiogram, and urinalysis. If systemic illness is present, the treatment is optimized. Often, an anaesthesi-ologist will examine the patient and the record before treatment, obtaining a separate anaesthesia consent. Although no medical examinations relative to the ECT process are required, some centers unnecessarily insist on pre-treatment brain scans and EEG for all patients.
Anaesthesia . When curare and succinylcholine were introduced 
to modify the convulsion, patients thought they were suffocating as respiratory muscles relaxed. Momentary amnesia was provided by a barbiturate and the combination of barbiturate-induced amnesia and succinylcholine muscle relaxation became standard procedure.
(8,12)  When psychiatric practice changed from an ofﬁ  ce

(8,12)  When psychiatric practice changed from an ofﬁ  ce 
to a hospital venue, and anaesthesiologists administered medica-tions, misunderstanding of the role of anaesthesia ensued and the beneﬁ  ts of treatments were reduced by high anaesthetic doses that 
made effective seizures difﬁ  cult. Present practice is detailed in 
anaesthesiology texts.
(44)
Monitoring and electrode placement . T o monitor the physiologic 
effects of induced seizures, EEG and ECG electrodes are applied. T o monitor the motor seizure, a blood pressure cuff is usually applied to the calf of one leg, inﬂ  ated before the administration of a motor 
relaxant to observe the motor seizure duration. Two stimulating electrodes are required for ECT. In the early years, the electrodes were applied to both temples, w ith the maximum energies passing 
through the intervening brain tissues, esp ecially the centrencephalic

through the intervening brain tissues, esp ecially the centrencephalic 
structures of the hypothalamus and pituitary. Relocating the elec-trodes on one side of the head to avoid stimulating the dominant temporal lobe led to seizures with less immediate impact on cogni-tion. ‘Right unilateral ECT’ (RUL-ECT) became popular until clinicians realized that the efﬁ  cacy of such treatments was signiﬁ  -
cantly less than through bilateral electrodes (BL-ECT).
(8,12)
At one time we believed that any seizure was therapeutic, but 
we now know that this is not so. A seizure with EEG or motor dura-tions under 20 sec rarely develops a full grand mal convulsion. At ﬁ rst, effective treatments were characterized as those with a

we now know that this is not so. A seizure with EEG or motor dura-tions under 20 sec rarely develops a full grand mal convulsion. At ﬁ rst, effective treatments were characterized as those with a 
motor seizure of at least 25 sec. But not all seizures of such length are effective. Seizures induced through unilateral electrodes at near-threshold energies (experimentally identified as 1.5 and 2.5 times the calibrated seizure threshold) are not as effective as seizures induced through bilateral electrode placements.
(45)
Energies for seizure inductions in unilateral ECT must be at least 6 to 8 times the calibrated seizure threshold to achieve equal efﬁ  cacy; 
at such high energies the advantage in minimizing immediate 
memory effects is lost.
(46) As there is a linear relationship between 
age and seizure threshold, the energy levels with modern devices that deliver brief pulse electrical currents for BL-ECT is estimated by the half-age formula.

(47) In devices that deliver 500 mC of energy 
at 100 per cent, the energy level for the ﬁ  rst induction is set at half 
the patient’s age. The quality and duration of the EEG seizure are a guide to later induction energies. In present clinical practice, electrodes are applied to both temples (BT-ECT) or over the outer canthus of each eye in ‘bifrontal’ (BF-ECT) placement. While the

1257
advantages of BF-ECT and BT-ECT are being assessed in large 
studies, their efﬁ  cacy seems equivalent. There is little justiﬁ  cation 
for the use of RUL-ECT in clinical practice.
We now rely on the ictal EEG to deﬁ  ne an effective treatment, 
and modern ECT devices record either one or two channels of brain electrical activity. The typical ictal EEG presents a build-up of energies, then high-voltage spike activity mixed with high-voltage slow waves (3–6 Hz), followed by trains of lesser voltage slow waves, and an abrupt end to the electrical activity with electri-cal silence. Such EEG patterns, generally of 35–130 sec in duration, are associated with motor seizures that are 10–20 per cent shorter. If seizures do not show these well-deﬁ  ned phases, we repeat the 
treatment at different energy settings until a robust EEG sequence is elicited.
(11–15)
A rise in the post-ictal serum prolactin is another index of

(11–15)
A rise in the post-ictal serum prolactin is another index of 
seizure adequacy. Grand mal seizures release brain peptides into the CSF and blood. Serum prolactin, easily measured, rises rapidly reaching a peak at about 25–30 min, and falls to a baseline level within 2 h. The absence of a dramatic rise in serum prolactin is a sign of inadequate treatment.
(48)
The ECT course . Occasionally a single treatment relieves a disor-
der, but such instances are so rare as to be noteworthy. The basic course is more often between 6 and 20 treatments. These are usu-ally given three times a week at the onset and, after the symptoms show some relief, are reduced to twice or once a week. The resolu-tion of catatonia (MC, NMS) is frequently accomplished in three to ﬁ ve treatments but these are best administered daily. Depressive

disorders require 6–12 treatments for resolution. Manic and psy-chotic disorders require 20 or more treatments.
Discontinuing treatment at the point of immediate resolution 
of symptoms is associated with high relapse rates. Continuation treatment, often continuation ECT, is as essential a part of ECT management as it is for pharmacotherapy.
(49,50)
Continuation treatments . High relapse rates are the most com-
mon complaint in ECT practice. When patients are given a short course of treatments, early relapse is common. Because ECT is complex, frightening, and expensive, patients seek the shortest course of treatment, and physicians accede by prescribing a limited number of treatments on referral or at the time the patient signs the consent.
(4)
Short courses of treatments may relieve symptoms but relapse is 
quick.(49,50)  Continuation treatment is necessary. Two recent studies

(4)
quick.(49,50)  Continuation treatment is necessary. Two recent studies 
guide present practice. In a 3-hospital collaborative study of depressed patients referred for ECT, remitted patients were ran-domly assigned to 6-month courses of medication. Relapse rates were 84 per cent for placebo, 60 per cent for nortriptyline and 39 per cent for the combination of lithium and nortriptyline under serum level control.
(50) In the 4-hospital collaborative study, 
depressed patients treated with bitemporal ECT were randomly assigned to continuation with ECT or the same lithium and nortriptyline combination. The 6-month relapse rates were 32 per cent for continuation medication and 37 per cent for continuation ECT.
(49) These rates are statistically indistinguishable in the two 
studies.
ECT and psychotropic drugs .(12, 51)  With the exception of 
anti psychotics, we lack evidence of synergy between psychotropic drugs and ECT.

studies.
(11,12,14) TCA, MAOI, and SSRI antidepressants 
are usually discontinued during an ECT course. Anticonvulsants and sedative drugs affect seizure thresholds and may interfere with efﬁ cacy. ECT augmentation of antipsychotics is seen as safe and 
When ECT is administered to a patient with clinically effective 
serum lithium levels, generally seen as 0.8–1.2 mEq/l, there is the 
risk of a post-seizure delirium. If lithium treatment is sustained during ECT, the dosages are reduced so that the serum lithium levels do not rise above 0.6 mEq/l on treatment days.
Systemic drugs, especially those used to treat cardiovascular 
disorders, may put the patient at risk for hypotension, ataxia, or exaggerated cognitive deﬁ  cits, but these effects can be easily managed, 
so they are usually continued during ECT.

Inducing adequate seizures in patients who have been receiving 
benzodiazepines may be difficult. Intravenous flumazenil, the benzodiazepine antagonist, effectively minimizes the inhibiting effects of benzodiazepines. Such use is encouraged for patients with catatonia or mania who have been treated with benzodiazepines.
(9)
Risks and contraindications
Bone fractures, tardive seizures, and cardiac arrhythmias were 
common risks of early ECT, but the routine use of muscle relaxa-tion with succinylcholine markedly reduced them.
(8,12) Headache,

(8,12) Headache, 
tongue injury, and post-seizure delirium continue to be systemic risks. Headaches respond to analgesics, delirium to benzodi-azepines, and tongue injury can be prevented by the proper appli-cation of bite-blocs. The principal risks of ECT today are cognitive effects and unacceptable relapse rates.
In a post-seizure delirium, which occurs in about 10 per cent of 
the treatments, the patient is poorly aware of where he is and may thrash about and be confused. It is more common in the ﬁ  rst and 
second treatments than in later ones. Reassurance, calm talk, and gentle handling of movements that might be harmful can usually allay such states. If the restlessness does pose risks, it can be calmed by intravenous diazepam.
Persistent amnesia is the most dreaded risk of ECT.
(12–15) Patients

(12–15) Patients 
usually forget the personal events that occurred during the illness and treatment. On treatment days, both the anesthesia and the seizure alter cognition, temporarily interfering with the memory of events. In the ﬁ  rst decades of ECT use, adequate ventilation was 
not assured and untoward effects on cognition were profound and frequent. But changes in practice have reduced these effects. Ventilation with pure oxygen, changes in the type of electrical cur-rent and the amounts of energy, and selected electrode placement reduced the effects on cognition, so that within a few weeks after the course is over, the patients’ performance on memory tests usu-ally surpasses their pre-treatment abilities.
Contraindications . There are no systemic illnesses that preclude 
the administration of ECT when the treatment is clearly warranted. Some conditions — severe hypertension, uncontrolled cardiac

the administration of ECT when the treatment is clearly warranted. Some conditions — severe hypertension, uncontrolled cardiac 
arrhythmia, bleeding tendencies, recent myocardial infarction, 
increased intracranial pressure, and a brain or cerebrovascular lesion — call for special care. The case literature offers suggestions for the appropriate treatment with ECT of patients with these conditions.
(12–15)
Mechanism of action
When convulsive therapy was introduced, its most prominent side effect was amnesia, and much debate centered on whether amnesia 6.2.10.1 electroconvulsive therapy

SECTION 6  treatment methods in psychiatry 1258
was, in fact, the mechanism for improving thought and mood. 
Experiments with different electrode placements discouraged this explanation.
(4,12)
Others focused on the physiologic effects of seizures, especially 
the changes in the interseizure EEG. Such changes were found to be necessary, but not sufﬁ  cient, for recovery.
(8, 52) Interest in this 
hypothesis is revived by recent studies.(53)
Explanations based on neurohumours and their receptors are 
important in our present views of the action of drug therapies. These are also cited to explain the beneﬁ  ts of ECT. The experimental 
data fail to support these explanations.
(8, 12, 54)
Meduna thought that the concentration of glia was a factor in 
illness and that seizures elicited increased gliosis and recovery.(6)
Recent reports cite increased neurogenesis as an active brain response to induced seizures.
(55)
My view is that the neuroendocrine system is the most likely

(55)
My view is that the neuroendocrine system is the most likely 
agent for the clinical changes brought about by induced sei-zures.
(8,56)  Neuroendocrine dysregulation is prominent in patients 
with the mental disorders for which ECT is effective. Thyroid, adrenal, sex gland, and hypothalamic dysfunction are common in patients with disorders in mood, thought, motor activity, feed-ing, sleep, sex, growth, and maturation. Indeed, every aspect of body physiology and mental activity is affected by these glands, as exempliﬁ  ed by the action of the adrenal glands in depressive mood 
In the severely depressed patients, the adrenal glands produce 
too much cortisol.
(17, 18, 56) The high blood levels disrupt the

(17, 18, 56) The high blood levels disrupt the 
normal diurnal rhythms of other glandular discharges, and the glands do not respond to the usual feedback mechanisms. The most prominent features of depression — failure to eat, loss of weight, inability to sleep, loss of interest in sex, inability to concen-trate thoughts, and difﬁ  culties in memory — are distortions of the 
functions regulated by the neuroendocrine glands in a self-adjusting feedback.
Each seizure stimulates the hypothalamus to discharge its 
hormones, which causes the pituitary gland to discharge its prod-ucts, which then affects the level of cortisol. The ﬁ  rst effects of this 
cascade are transitory, but repeated seizures restore the normal interactions of the hypothalamic-pituitary-adrenal axis. Feeding and sleep become normal, followed by motor activity, mood, 
memory, and thought.

How does a seizure elicit such profound changes in physiology? 
In ECT, the currents from the stimulating electrodes on each temple pass through the central parts of the brain, stimulating both the hypothalamus to discharge its hormones and the centren-cephalic structures to produce a bilateral grand mal seizure. (One of the ﬂ  aws in unilateral electrode placement is that the currents 
have to take indirect routes to affect the pertinent areas of the brain.) The massive amounts of hypothalamic and pituitary hormones that enter the bloodstream during ECT are measurable within a few minutes. They circulate throughout the body, affecting all the body’s cells — a compelling and welcome sign of recovery.
After some courses of ECT, the return to normal endocrine func-
tion persists. At other times, the glands revert to their abnormal

tion persists. At other times, the glands revert to their abnormal 
activities and the mental disorder becomes evident again. In these cases, repeated stimulation of the hypothalamus and the pituitary by continuation ECT restore and sustain normal glandular func-tions and support a normal mental state.Suggested replacements for ECT
Although Meduna’s experiments and numerous studies of ECT and sham ECT support the seizure as evidence of the brain changes essential to a therapeutic beneﬁ  t, the introduction of electricity 
focussed attention away from the seizure and onto electricity as the medium for the treatment’s efﬁ  cacy. This interest is not new. Soon 
after Galvani and Volta demonstrated that electric currents could stimulate nerves and muscles, medical applications were enthusias-tically sought. The ﬁ  rst electrical experiments in the mentally ill

are ascribed to Gale in New Y ork State in 1802 and Aldini in Italy in 1803.
(3,16,54) Electrical experiments were publicly demonstrated 
by Franklin, Mesmer, and Marat in the ﬁ  rst years of the 19th century. 
Little beneﬁ  t was recorded and most efforts are best considered 
quaint explorations.(3) At the time of World War I, faradization was 
a treatment for hysteria and applied in the military.(57)
During the second half of the 20th century, many techniques have 
been suggested as replacements for ECT, the lat est bein g transcranial
magnetic stimulation (rTMS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS).
(58) In rTMS rapidly alternating 
magnetic ﬁ  elds are delivered to stimulate the brain. At very high

magnetic ﬁ  elds are delivered to stimulate the brain. At very high 
intensities, a seizure may be induced and some experiments have been undertaken to compare the seizure induced by magnetic currents with those induced by electric currents. The technique, called magnetic seizure therapy (MST), is reported to have a mild antidepressant effect.
(58)
In VNS an electrical stimulator is implanted in the chest wall and 
electrodes are threaded through the neck to the left vagus nerve. The stimulator is similar to that used to reduce seizures in patients with severe epilepsy. The side effects of hoarseness, nausea, and vomiting are common. In DBS, the stimulating electrodes are placed in the brain, a technique occasionally used in severe Parkinsonism. We lack sufﬁ  cient evidence for the efﬁ  cacy of rTMS, VNS and DBS in

psychiatric disorders to warrant their routine clinical use.
Device manufacturers who seek a market for their products 
encourage the technologies. The bad image and the stigma of ECT make its replacement the basis for exploration. At the time of this writing (Spring, 2007), no evidence has been published that any of these techniques have persistent therapeutic effects, and none are replacements for ECT.
The future in ECT
Induced seizures effectively allay severe psychiatric disorders. The treatment’s stigma, however, inhibits its use and research into its mechanism. When neuroscientists recognize the unique nature of the seizure — a phenomenon that is ubiquitous in animal life — and seek to understand its biology, they will then seek ways to replace 
the gross process of induced seizures by more acceptable interven-tions. Understanding the mechanism will clarify the aetiology of psychiatric disorders. ECT will be replaced when we understand its

the gross process of induced seizures by more acceptable interven-tions. Understanding the mechanism will clarify the aetiology of psychiatric disorders. ECT will be replaced when we understand its 
mechanism better; for the present, continued usage is assured since no alter native intervention with its efﬁ  cacy and safety is in our 
materia medica .
Abrams, R. (2001). Electroconvulsive Therapy  (4th edn.). Oxford University 
Press, New Y ork

1259
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American Psychiatric Pub, Washington, DC.
6.2.10.2 Phototherapy
Phototherapy or artiﬁ  cial bright-light treatment, has been used in 
the management of a number of medical disorders including pso-riasis and hyperbilirubinaemia of the newborn. From the point of view of psychiatric treatment, the notion that light might help peo-ple with certain psychological symptoms has an ancient lineage. For example, Wehr and Rosenthal
(1) cite Aretaeus who suggested in 
the second century ad that ‘lethargics are to be laid in the light and 
exposed to the rays of the sun (for the disease is gloom)’ . In 1898, a ship’s physician named Frederick Cook recorded that the ‘lan-
guor’ which affected members of an Antarctic expedition during the winter darkness could be relieved with bright artiﬁ  cial light.
(1)

(1)
The ﬁ  rst systematic study of phototherapy as a psychiatric treat-
ment was carried out in 1984 by Rosenthal et al.(2) who used bright 
artiﬁ cial light to treat patients with the newly identiﬁ  ed syndrome 
of seasonal affective disorder. Seasonal affective disorder is a recur-rent mood disorder in which patients experience regular episodes of depression in autumn and winter with remission in spring and summer. Since then phototherapy has become the mainstay of the treatment of seasonal affective disorder, particularly in patients with atypical depressive features such as hyperphagia and hyper-somnia. Phototherapy has also been used as an investigational treatment in other psychiatric disorders but the evidence for its efﬁ cacy in these conditions less established.
Light and seasonal and circadian rhythms

Animals and humans show circadian and seasonal rhythms in 
aspects of their physiology and behaviour that are inﬂ  uenced by 
environmental cues or zeitgebers . The light–dark cycle is believed to 
be one of the most important zeitgebers  regulating circadian and 
seasonal rhythmicity in mammals. Mammalian circadian rhythms are driven by an ‘oscillator’ in the suprachiasmatic nucleus of the hypothalamus. Environmental light inﬂ  uences the activity of this 
nucleus via a neuronal pathway which runs from the retina to the hypothalamus. Thus appropriately timed bright light is able to advance or delay endogenous circadian rhythms.
(3)
Lewy et al .(4) suggested that in patients with seasonal affective 
disorder the delayed onset of dawn in the autumn causes endoge nous

(3)
circadian rhythms to become phase-delayed with respect to clock time and the sleep–wake cycle. Bright-light treatment is able to correct this abnormality by phase advancing circadian rhythms, thereby re-synchronizing them with the sleep–wake cycle. This proposal is supported by the fact that controlled trials show that in most patients morning phototherapy is more effective than eve-ning phototherapy.
(5) While this hypothesis gives a good account 
of how bright-light treatment might ameliorate the symptoms of seasonal affective disorder, its possible efﬁ  cacy in other condi-
tions such as non-seasonal depression is difﬁ  cult to explain by this 
mechanism.
Light treatment and monoamines

It is possible that bright-light treatment, through its interaction with the hypothalamus, could alter the circadian activity of the monoamine neurotransmitters involved in mood regulation. For example, some studies have shown that the antidepressant effects of phototherapy can be reversed by treatments that diminish both catecholamine and serotonin neurotransmission.
(6)
This has been taken as evidence that the antidepressant effects of bright light are mediated via activation of serotonin and catechol-amine pathways. An alternative explanation is that in the absence of concomitant drug treatment, recovered depressed patients are vulnerable to depletion of these neurotransmitters in any case. However, effects of bright light on monoamines could account for the therapeutic effects of light in mood disorders other than winter depression.

1261
Forms of phototherapy
The most common form of phototherapy uses a light box, 
which contains ﬂ  uorescent tubes mounted behind a translucent 
plastic-diffusing screen. Depending on the fluorescent tubes employed, the light emitted is either full spectrum, which contains a little ultra violet light, or cool white light which has no ultraviolet. The light box usually rests on a table or desk at about the eye level of a seated subject. The output of different light boxes varies but is usually between 2500 and 10 000 lux. Light sources produc-ing 10 000 lux are more expensive but allow a reduced duration of exposure (30 min compared with 120 min) to secure a therapeutic effect.
(7)
Phototherapy has also been administered using head-mounted

(7)
Phototherapy has also been administered using head-mounted 
units or light visors. These instruments are attached to the head and project light into the eyes allowing subjects to remain mobile while receiving treatment. While light visors are more convenient to use than light boxes, results from placebo-controlled trials have not been encouraging.
(7)
Another form of light therapy involves the use of dawn-simulating
alarm clocks. These clocks are programmed to simulate the illumi-nation that would be experienced out of doors during sunrise on a spring day.
(8) In practice, the clocks begin a gradual illumination 
of the bedroom about 2 h before normal wake time, increasing to a maximum of about 250 lux at the point of waking. Overall the effects of dawn-simulation in the treatment of winter depression seem equivalent to those of bright-light treatment
(9) and patients 
often ﬁ  nd dawn-simulating clocks more convenient (although a 
partner sleeping in the same room may not).

Generally phototherapy is well tolerated although mild side effects occur in up to 45 per cent of patients early in treatment. These include headache, eye strain, blurred vision, eye irritation, and increased tension. Insomnia can occur particularly with late-evening treatment. Rare adverse events that have been reported include manic mood swings and suicide attempts, the latter puta-tively through light-inducing alerting and energizing effects prior to mood improvement. Whether these rare events are actually adverse reactions to the light is uncertain. There is no evidence that phototherapy employed in recommended treatment schedules causes ocular or retinal damage .
Indications and contraindications to light 
treatment
The best established indication for light treatment is seasonal

treatment
The best established indication for light treatment is seasonal 
affective disorder where patients experience autumn and winter depressions. Clinical predictors of a response to light treatment include the following:
◆ Increased sleep
◆ Increased appetite and winter weight gain
◆ Carbohydrate craving
◆ Afternoon slump in energy
◆ Complete remission of symptoms in the summerSeveral controlled trials have assessed the efﬁ  cacy of bright-light 
treatment in the treatment of winter depression. In a meta-analysis of nine randomized studies, Golden et al .
(9) found a signiﬁ  cant 
beneﬁ  t of bright light over dim light control with an effect size of 
0.84 (95 per cent conﬁ  dence interval, 0.6–1.08). A similar beneﬁ  t 
was apparent for six studies of dawn simulation which had a mean effect size of 0.73 (95 per cent conﬁ  dence interval, 0.37–1.08).

was apparent for six studies of dawn simulation which had a mean effect size of 0.73 (95 per cent conﬁ  dence interval, 0.37–1.08). 
While these data are compelling it needs to be remembered that it is often difﬁ  cult to arrange a placebo treatment that will match the 
therapeutic expectation of bright light or dawn simulation.
Other mood disorders
Patients with more typical melancholic symptoms (e.g. weight loss and insomnia) do less well with bright-light treatment, even when the disorder is seasonal in nature. However, bright light has also been used in the treatment of non-seasonal depression both as a sole treatment as an adjunct to more conventional therapy. The evidence for the efﬁ  cacy of bright light for this indication is less 
established but a Cochrane review
(10) suggested that morning light 
treatment was signiﬁ  cantly better than control treatment when

treatment was signiﬁ  cantly better than control treatment when 
applied as an adjunct to drug treatment or sleep deprivation. Most of these studies were of short-term duration and there are sugges-tions that the added beneﬁ  t of light therapy does not persist 
when treatment stops.
(11) In these studies, hypomania was more 
common in light-treated subjects. Phototherapy may also be of beneﬁ  t in other conditions characterized by depressed mood and 
overeating (e.g. premenstrual dysphoria and bulimia nervosa). The literature contains reports of a number of controlled trials in such disorders where light treatment has improved depression ratings. However, the difﬁ  culty of distinguishing the speciﬁ  c and placebo 
effects of bright-light treatment relative to dim light control makes the current data difﬁ  cult to interpret.
Circadian rhythm disorders

Because bright light is an effective zeitgeber  for circadian rhythms 
it may also have a useful place in the treatment of disorders characterized by circadian rhythm disturbances. Such disorders encompass a range of conditions including phase-delayed or phase-advanced sleep disorder, jet lag, and problems related to shift work. In addition, disturbances of the sleep–wake cycle are common in older people with cognitive impairment. There are several reports of the utility of light treatment in these conditions; however, there is a paucity of randomized trial data.
(7)
There are no absolute contraindications to phototherapy, except the obvious caveat that since the therapeutic effect depends on retinal activation, subjects must have sufﬁ  cient visual function to

There are no absolute contraindications to phototherapy, except the obvious caveat that since the therapeutic effect depends on retinal activation, subjects must have sufﬁ  cient visual function to 
allow this to occur. Otherwise it would seem prudent to avoid phototherapy in patients with pronounced and untreated agitation because this symptomatology could be worsened. In addition, evening phototherapy may worsen insomnia.
A substantial minority of patients with seasonal affective disorder 
meet criteria for bipolar II disorder, raising the concern that photo-therapy may trigger hypomania in such individuals. Particular caution might be needed in patients with a bipolar I syndrome. Some regimes of phototherapy might lead to a degree of sleep deprivation which could also destabilize mood in bipolar patients.6.2.10.2 phototherapy

SECTION 6  treatment methods in psychiatry 1262
One of the advantages of phototherapy in seasonal affective disorders 
is that the use of antidepressant drugs may be avoided. Despite this, many patients with winter depression use phototherapy con-comitantly with antidepressant medication without an obvious potentiation of adverse effects. However, a case report described apparent serotonin toxicity where phototherapy was combined with selective serotonin re-uptake inhibitors.
(7)
Like bright light, the pineal hormone, melatonin, also has the 
ability to shift the timing of circadian rhythms(2) and theoretically 
melatonin taken at an inappropriate time of day could offset the antidepressant effect of light. It is also possible that bright-light treatment could exacerbate the ability of some drugs (e.g. chlorprom-azine, St John’s Wort) to cause skin photosensitivity reactions.
(7)
Effects of withdrawal of phototherapy

(7)
If a patient with seasonal affective disorder responds to light treat-ment, withdrawal of treatment during the period of seasonal vulnerability leads to a return of symptomatology within a few days. It may be possible, however, to lessen the daily duration of treatment particularly towards the end of winter without inducing relapse. Otherwise cessation of light treatment does not seem to cause a speciﬁ  c withdrawal syndrome.
Administration of phototherapy
Since the best established indication for phototherapy in psychiatry 
is seasonal affective disorder, the following account will describe the use of bright-light treatment in winter depression. One of the major practical difﬁ  culties in phototherapy is the time needed to

administer treatment. For this reason a 10 000 lux light box may be preferred because the daily duration of treatment can be reduced to 30 min. It seems likely that cool-white light and full-spectrum light have equivalent clinical efﬁ  cacy, but because cool-white light 
is free of ultraviolet light it is theoretically safer and should be preferred.
The balance of evidence suggests that bright-light treatment of 
winter depression is most effective when administered in the early morning.
(4) However, treatment given later in the day may be 
effective for some patients. In an initial trial, therefore, it is best to recommend early morning treatment but to advise the patient that the timing of therapy can eventually represent a balance of thera-peutic efﬁ  cacy and practical convenience. Treatment in the late 
evening should be avoided because of the possibility of sleep disruption.
Early-morning phototherapy should start a few minutes after

Early-morning phototherapy should start a few minutes after 
waking. Subjects should allow themselves a 30 min duration of treatment with a 10 000 lux light source. They should seat them-selves about 30 to 40 cm away from the light box screen. They should not gaze at the screen directly but face it an angle of 45° and glance across it once or twice each minute.
The antidepressant effect of light treatment usually appears in a 
few days but in controlled trials up to 3 weeks can be needed before 
the therapeutic effects of bright light exceed those of placebo treatment. If no beneﬁ  t is noted after the third week of therapy, 
light treatment should probably be abandoned. As noted above mild side effects are common in the early stages of treatment but usually settle without speciﬁ  c intervention. If they are persistent

light treatment should probably be abandoned. As noted above mild side effects are common in the early stages of treatment but usually settle without speciﬁ  c intervention. If they are persistent 
and troublesome the patient can sit a little further away from the light source or reduce the duration of exposure. Exposure should also be reduced or stopped if elevated mood occurs.
Once a therapeutic response has occurred it is usually necessary 
to continue phototherapy up to the usual time of natural remission, otherwise relapse will occur. It may be possible, however, to lower the daily duration of treatment. Phototherapy can also be started in advance of the anticipated episode of depression as this may have a preventative effect; however, the evidence for this is limited and doubts have been expressed.
(7,12)
Centre for Environmental Therapeutics. http://www.cet.org.
Seasonal Affective Disorder Association. http://www.sada.org.uk.

(7,12)
Eagles, J.M. (2003). Reading about seasonal affective disorder. The British 
Journal of Psychiatry ,182, 174–6.
 1. Wehr, T.A. and Rosenthal, N.E. (1989). Seasonality and affective illness. 
The American Journal of Psychiatry ,146, 829–39.
 2. Rosenthal, N.E., Sack, D.A., Gillin, C., et al. (1984). Seasonal affective 
disorder: a description of the syndrome and preliminary ﬁ  ndings with 
light therapy. Archives of General Psychiatry ,41, 72–80.
 3. Arendt, J. and Broadway, J. (1987). Light and melatonin as zeitgebers  in 
man. Chronobiology International ,4, 273–82.
 4. Lewy, A.J., Sack, R.L., Miller, S.L., et al.  (1987). Antidepressant and 
phase-shifting effects of light. Science ,206, 710–13.
 5. T erman, J.S., T erman, M., Lo, E.S., et al.  (2001). Circadian time of

 5. T erman, J.S., T erman, M., Lo, E.S., et al.  (2001). Circadian time of 
morning light administration and therapeutic response in winter depression. Archives of General Psychiatry ,58, 69–75.
 6. Neumeister, A., Turner, E.H., Matthews, J.R., et al. (1998). Effects of 
tryptophan depletion versus catecholamine depletion in patients with seasonal affective disorder in remission with light therapy. Archives of 
General Psychiatry ,55, 524–30.
 7. Eagles, J.M. (2004). Light therapy and the management of winter 
depression. Advances in Psychiatric Treatment ,10, 233–40.
 8. T erman, M. and T erman, J.S. (2006). Controlled trial of naturalistic 
dawn simulation and negative air ionization for seasonal affective disorder. The American Journal of Psychiatry ,163,
2126–33.
 9. Golden, R.N., Gaynes, B.N., Ekstrom, R.D., et al. (2005). The efﬁ  cacy 
of light therapy in the treatment of mood disorders: a review and

2126–33.
of light therapy in the treatment of mood disorders: a review and 
meta-analysis of the evidence. The American Journal of Psychiatry ,
162, 656–62.
10. Tuunainen, A., Kripke, D.F., and Endo, T. (2007). Light therapy for 
non-seasonal depression. http://www.cochrane.org.reviews/en/
ab004050.html.
11. Martiny, K., Lunde, M., Unden, M., et al.  (2006). The lack of sustained 
effect of bright light in non-seasonal major depression. Psychological 
Medicine ,36, 1247–52.
12. Partonen, T. and Lonnqvist, J. (1996). Prevention of winter seasonal 
affective disorder by bright-light treatment. Psychological Medicine ,
26, 1075–80.

1263
6.2.10.3 Transcranial 
magnetic stimulation
Transcranial magnetic stimulation (TMS) is a means of non-
invasively stimulating the cerebral cortex using a hand-held coil applied to the scalp. In recent years TMS has been increasingly used to target neuronal circuitry implicated in neuropsychiatric disorders.
A key milestone in the development of TMS occurred in 1831 
when Michael Faraday discovered the phenomenon of electromag-netic induction whereby a time-varying magnetic ﬁ  eld can induce 
electrical currents through a conductor lying in proximity to the ﬁ  eld. The French biophysicist D’Arsonval in 1896 induced 
phosphenes, vertigo, and syncope in human subjects by placing an induction coil around their heads. In the late 1950s, Kolin stim-ulated peripheral nerves (the frog sciatic nerve) with a magnetic ﬁ eld and a few years later the same technique was used in human

subjects, inducing muscle twitching by applying a pulsed magnetic 
ﬁ eld over the ulnar, peroneal, and sciatic nerves.
In the mid-1980s, Barker and colleagues in Shefﬁ  eld developed 
a magnetic stimulator to directly stimulate the human motor cortex.
(1) They applied a circular coil, through which a large (4000 A), 
brief (110 μs) current was passed to the scalp. The resulting pulsed magnetic ﬁ  eld was used to stimulate the motor cortex, evoking 
movements in the contralateral limbs and is known as transcranial magnetic stimulation. This ability to non-invasively stimulate the motor cortex with a magnetic ﬁ  eld soon replaced high-voltage

movements in the contralateral limbs and is known as transcranial magnetic stimulation. This ability to non-invasively stimulate the motor cortex with a magnetic ﬁ  eld soon replaced high-voltage 
transcutaneous electrical stimulation for assessing central motor conduction times and mapping corticospinal pathways in a variety of neurological conditions. In the late 1980s machines capable of delivering multiple TMS pulses were developed. Repetitive TMS (rTMS), unlike single pulses of TMS can produce effects that last after the period of stimulation. For example, it has been shown that rapid rTMS (at frequencies of 5 Hz and greater) enhances motor excitability whereas slow rTMS (at 1 Hz 
or less) transiently depresses excitability.
(2) The underlying princi-

ple of rTMS treatment is that the normal balance of excitatory and inhibitory processes within certain neuronal pathways may be disrupted in psychiatric conditions such as depression. Stimulating the brain using rTMS provides a means of increasing and decreasing excitation and inhibition in these pathways, having a neuromodulatory effect and allowing a focal targeting of speciﬁ  c 
neuronal circuitry.
The underlying mechanisms of the effects of rTMS remain poorly understood. This is in part because, as with attempting to under-stand the mode of action of psychotropic medication, it is difﬁ  cult

The underlying mechanisms of the effects of rTMS remain poorly understood. This is in part because, as with attempting to under-stand the mode of action of psychotropic medication, it is difﬁ  cult 
to establish links between cellular and physiological changes and alterations in emotion, thinking, and behaviour. T echniques used to try to better understand the molecular and physiological effects of rTMS have included neuroimaging and animal studies.Neuroimaging has demonstrated that rTMS may exert effects on 
the brain at a considerable distance from the site of stimulation. For example, serial positron emission tomography scanning has been used to measure regional cerebral blood ﬂ  ow in medication-
free patients with major depression before and after courses of fast and slow rTMS administered over the left prefrontal cortex.
(3)
It has been demonstrated that fast rTMS causes increases in regional 
cerebral blood ﬂ  ow in bilateral frontal, limbic, and paralimbic areas

(3)
cerebral blood ﬂ  ow in bilateral frontal, limbic, and paralimbic areas 
whereas slow rTMS caused decreases in blood ﬂ  ow in the right pre-
frontal cortex, left medial temporal cortex, and left basal ganglia and amygdala.
It has been suggested that rTMS of the left prefrontal cortex may 
modulate brain function by an effect on dopamine release. Elevated extracellular dopamine concentrations in the dorsal hippocampus have been demonstrated in the brains of rats who received rTMS. However, one of the problems with using animal models of rTMS is that currently small rTMS coils are not available and it is there-fore impossible to focally stimulate one particular area of the small rodent brain. In humans it has been shown that rTMS to the 
dorsolateral prefrontal cortex can induce the release of dopamine 
in the ipsilateral caudate nucleus.
(4)

(4)
Being non-invasive and not requiring a general anaesthetic, rTMS is considered to be a relatively safe treatment and few side-effects have been reported. The most signiﬁ  cant potential side-effect is the 
risk of unintended seizure induction. There have been six reports to date of seizure induction in healthy volunteers. In half of these, very high stimulation intensities and frequencies were used. There have only been three reports of seizures in patients receiving rTMS and one of these patients had a pre-existing diagnosis of temporal lobe epilepsy. Researchers generally follow safety guidelines that exclude high-risk patients, (e.g. those with a stroke, brain tumour or pre-existing epilepsy) from receiving rTMS. These guidelines also suggest limits to the intensity, frequency, and stimulus duration of the rTMS used.
(5)

(5)
The most common side-effect of rTMS is headache or facial dis-
comfort that is the result of direct stimulation of muscle and nerves in proximity to the coil. Approximately 10–30 per cent of subjects experience these symptoms, which are generally short-lived and well-tolerated.
Technique
rTMS equipment comprises a stimulator unit, booster modules, a laptop computer, and a ﬁ  gure-of-eight coil. The stimulator unit 
contains the charging circuitry, energy storage capacitors, control electronics and discharge, and safety circuitry. It is connected to booster modules, which charge the high-voltage capacitors, enabling trains of high-intensity magnetic stimulation to be produced. The stimulating coil consists of tightly wound copper wire in a figure-of-eight through which a rapidly alternating electric current passes to produce a pulsed magnetic ﬁ  eld. Various

stimulation parameters including train duration, frequency of stimulation, stimulus intensity, and length of inter-train interval can be altered using computer software.
rTMS treatment is delivered via the ﬁ  gure-of-eight coil applied 
to the scalp surface. Typically, prior to treatment, TMS will be used 6.2.10.3 transcranial magnetic stimulation

SECTION 6  treatment methods in psychiatry 1264
to map the motor area of the right abductor pollicis brevis (APB), 
and measure its motor threshold. The stimulus intensity delivered during treatment is then calculated in relation to this motor thresh-old. The main method of localizing the stimulation site has been to use a ﬁ  xed point in anatomical relation to a speciﬁ  c motor area, for 
example the dorsolateral prefrontal cortex has generally been deﬁ ned as the point 5 cm anterior to the APB motor area in the 
parasaggital plane. More recently some studies have used magnetic resonance imaging to more accurately delineate the area to be stimulated.
rTMS and depression
Transcranial magnetic stimulation was ﬁ  rst postulated to have 
potential applications in psychiatry by Bickford and colleagues who noted transient elevation in mood in several healthy subjects who had received single pulses of TMS to the motor cortex.
(6) Several

(6) Several 
small open studies followed that suggested that low frequency rTMS over the vertex may have antidepressant effects. Since the mid 1990s most interest has focussed on high-frequency rTMS applied to the left dorsolateral prefrontal cortex (LDLPFC), a region reported to be underactive in depression. T o date there have been approximately 30 randomized trials of real and placebo rTMS in depression. In addition there have been several published meta-analyses including a Cochrane review.
(7) This reviewed 16 trials,

(7) This reviewed 16 trials, 
14 of which were suitable for quantitative analysis. They found that high-frequency rTMS to the LDLPFC and low-frequency rTMS to the right dorsolateral prefrontal cortex (RDLPFC) were both superior to sham treatment but only for one measure (the Hamilton Depression Rating Scale) and at one time point (immediately after 2 weeks of treatment). The difference between real and sham was not large, leading to the conclusion that at this stage there was not strong evidence to support the use of rTMS as an antidepressant therapy.
There has been considerable heterogeneity between studies. 
Nearly all the trials have comprised patients with major depressive disorder defined using DSM-IV criteria. However there has been considerable variability with respect to pharmacotherapy received, with some trials specifying treatment resistance (variously 
deﬁ ned) and some specifying medication-free participants. In

deﬁ ned) and some specifying medication-free participants. In 
two of the studies patients were started on antidepressant treatment either shortly before or simultaneously with the rTMS treatment.
The choice of appropriate sham condition is an important 
methodological consideration. There are two main approaches. Most studies have relied on tilting the active coil (usually through 45° or 90° with one or both wings of the coil touching the scalp). However intracerebral voltage measurements in a rhesus monkey have shown that, depending on how the coil is tilted, sham condi-tions obtained by coil tilting can induce voltages in the brain to levels only 24 per cent below active rTMS.
(8) The fact that some 
‘sham’ coils produce signiﬁ  cant cortical stimulation may account 
for some of the beneﬁ  t seen in those receiving sham stimulation

for some of the beneﬁ  t seen in those receiving sham stimulation 
and may underestimate the difference between real and placebo treatment. The other approach is to use a specially designed place-bo coil. This looks identical to the real coil and makes the same noise but does not cause any cortical stimulation. However, neither does it cause sensation to the scalp, meaning that subject blinding may still be less effective. Indeed the problem of maintaining blinding in studies with rTMS continues to be a major method-
ological issue.
Most studies have given high-frequency rTMS to the LDLPFC, 
probably as a result of the positive early studies when this area was

probably as a result of the positive early studies when this area was 
stimulated. Several investigators have used low-frequency rTMS to the RDLPFC. Low-frequency rTMS is much less likely to induce a seizure and is probably better tolerated by patients. Since slow rTMS has an inhibitory effect in contrast to the excitatory effect of fast rTMS and since there is considerable evidence that the left and right hemispheres have contrasting functions in regulating mood, it could be speculated that slow rTMS to the right cortex may have a similar effect to fast rTMS to the left.
Studies of high-frequency rTMS in depression have generally

Studies of high-frequency rTMS in depression have generally 
used stimulation frequencies of 5 to 20 Hz. There is a suggestion from animal studies that higher frequency stimulation may have a greater antidepressant effect but so far the numbers of subjects in human studies have been too low to show if a difference in effect of varying stimulation frequency exists. Likewise, the optimal stimulus intensity, length of treatment course, and total number of stimulations is not yet clear from the published data. However, longer trials with an increase number of stimulations appear to make little difference.
(9)
Most of the rTMS studies in depression have been small, the 
largest until recently having 70 patients. However, recently a much larger industry-sponsored (Neuronetics) trial submitted their ﬁ ndings to the US Food and Drug Administration (FDA), seeking

largest until recently having 70 patients. However, recently a much larger industry-sponsored (Neuronetics) trial submitted their ﬁ ndings to the US Food and Drug Administration (FDA), seeking 
licensing approval for an rTMS device. In this study 301 patients were randomized to real or sham rTMS. Participants received 10 Hz rTMS of the left dorsolateral prefrontal cortex, 3000 pulses per day for 20 days. Although there was a marginal difference between the groups in favour of rTMS at the end of treatment, there was no signiﬁ  cant group difference on an intention-to-treat 
analysis of the primary outcome measure (Montgomery-Åsberg Depression Rating Scale). In January 2007 the FDA Neurological Devices panel considered Neuronetic’s application to have its rTMS equipment licensed for therapeutic use. The panel felt 
that there was insufﬁ  cient evidence to support its efﬁ  cacy. The 
ﬁ nal FDA decision is expected in summer 2007 (website: http://

www.fda.gov/cdrh/panel/summary/neuro-012607.html, accessed: 5 June 2007).
In the United Kingdom the National Institute for Clinical 
Excellence (NICE) has issued recommendations stating ‘Current evidence suggests there are no major safety concerns associated with transcranial magnetic stimulation for severe depression but there is no evidence that the procedure has clinically useful efﬁ  cacy’ 
(website: http://www.nice.org.uk/article.aspx?o=ip346consultation, accessed: 5 June 2007).
Comparisons with ECT
In addition to comparisons with placebo treatment, rTMS has also been directly compared with ECT in several studies. While ECT is the most effective treatment for severe depression in the short-term its use is limited by several issues, including acceptability to patients, 
the requirement to be anaesthetized, and the occurrence of

the requirement to be anaesthetized, and the occurrence of 
side-effects, particularly cognitive side-effects. rTMS could be a potential alternative if it proved effective. In total there have been six published randomized controlled trials to date comparing ECT and rTMS. These trials have all had relatively small numbers of

1265
patients, particularly when compared with trials of antidepressant 
medications. They have either shown rTMS to be less effective or not statistically different from ECT. The most recent and largest trial to date included 46 patients and compared 3 weeks of treat-ment with rTMS to a course of ECT.
(10) The mean reduction in the 
Hamilton Depression Rating Scale achieved at the end of treatment was 14.1 points in the ECT group, compared with 5.4 points for the rTMS group, translating into a mean percentage reductions from baseline of 58 and 22 per cent, respectively. Overall, ECT was shown to be substantially more effective as a short-term treatment of depression than rTMS.
rTMS and schizophrenia
While most studies of rTMS within psychiatry have focussed on depression, there has been a growing interest in using rTMS as a possible treatment for schizophrenia. It has been used to treat both auditory hallucinations and to alleviate negative symptoms of schizophrenia.

Auditory hallucinations occur in approximately 70 per cent of 
patients with schizophrenia and in about a quarter of cases respond poorly if at all to antipsychotic medication. Recent advances in neuroimaging have enabled measurement of neural activity while hallucinations are being experienced and it has been demonstrated that auditory hallucinations are associated with activation in a number of brain areas, including the temporal cortex bilaterally. This area has been targeted in several rTMS studies using slow rTMS to reduce excitability.
The ﬁ  rst account of using rTMS to treat auditory hallucinations 
reported improvement in the severity of hallucinations of three patients with schizophrenia who had 40 min/day of 1 Hz rTMS 
over 4 days.
(11) There have now been 15 published treatment studies 
of rTMS targeting auditory hallucinations in schizophrenia. T en sham-controlled trials (involving 212 patients) were included in a recent meta-analysis

(12) which concluded that overall rTMS 
was signiﬁ  cantly better than sham stimulation in the treatment of 
auditory hallucinations.
Negative symptoms of schizophrenia include alogia, avolition, 
anhedonia, and affective ﬂ  attening and are associated with atten-

tional impairment and executive dysfunction. Negative symptoms are often resistant to neuroleptic medication and are associated with poor clinical outcome. There is increasing evidence that nega-tive symptoms are related to reduced cortical activation, particu-larly involving the left prefrontal cortex. Therefore one treatment approach has been to attempt to increase activation within this region. There have been four published randomized controlled studies comparing real and sham rTMS of the left dorsolateral prefrontal cortex to target negative symptoms of schizophrenia, of which three found no difference between real and sham treatments 
and one found 2 weeks of high-frequency rTMS signiﬁ  cantly 
improved negative symptoms. Novak et al .
(13) additionally per-

formed a battery of neuropsychological tests and follow-up patients for 6 weeks after treatment but found no signiﬁ  cant differences 
between treatment groups at either time point for primary or 
secondary outcome measures. The most recent study
(14) did not 
provide evidence that rTMS to the DLPFC improved negative symptoms of schizophrenia in patients with prominent negative symptoms but did suggest that rTMS may improve cognitive functioning in this patient group, at least in the short-term. However larger studies with longer periods of follow-up will be 
required to further examine this preliminary ﬁ  nding.
rTMS and obsessive–compulsive disorder
There have been several studies that have attempted to treat symp-

toms of obsessive–compulsive disorder (OCD) by modulating activity in prefrontal and motor circuits using rTMS. The earliest blinded trial of rTMS for OCD included 12 patients and found that a single session of right prefrontal high-frequency cortical stimulation signiﬁ  cantly decreased compulsive urges for over 8 h.
(15)
Obsessive thoughts did not change signiﬁ  cantly. This study sug-
gested that rTMS may be a useful probe of neuronal circuitry associated with symptoms of OCD. However a number of subse-quent studies have failed to replicate these ﬁ  ndings. A Cochrane 
review in 2003 examined three randomized controlled trials and concluded that there were currently insufﬁ  cient data to draw con-
clusions about the efﬁ  cacy of rTMS in the treatment of OCD.
(16)
The most recent, and largest trial of TMS in OCD to date

(16)
The most recent, and largest trial of TMS in OCD to date 
randomly allocated 33 patients with OCD to receive 10 sessions of either active or sham low-frequency (1 Hz) rTMS over the LDLPFC.
(17) This study did not demonstrate any difference 
between real and sham treatments.
rTMS and other neuropsychiatric disorders
rTMS has been postulated as a potential treatment in a variety of other neuropsychiatric disorders. There is emerging evidence that it may improve some of the motor symptoms of Parkinson’s disease. In a recent study six daily sessions of high-frequency rTMS were given to 55 unmedicated patients with Parkinson’s disease.
(18)

(18)
Patients received either 10 Hz or 25 Hz rTMS bilaterally to the motor cortex arm and leg areas or to the occipital cortex (control group). It was found that stimulation to the motor areas improved all measures, e.g. walking time, key-tapping speed, and self-assessment and that 25 Hz stimulation yielded greater improvement than 10 Hz. The effect was sustained for a month after treatment and restored by further booster sessions. The authors concluded that 25 Hz rTMS can lead to cumulative and long-lasting beneﬁ  ts on 
motor performance in Parkinson’s disease.
A recent study explored the effect of low-frequency rTMS to the 
left temperoparietal region on chronic tinnitus.
(19) Patients received 
1200 stimuli per day for 5 days of either real or placebo treatment in a randomized controlled crossover trial. Overall active rTMS induced a transient, but signiﬁ  cant improvement in the symptoms 
of tinnitus.
rTMS has also been used in an attempt to provide relief from

rTMS has also been used in an attempt to provide relief from 
chronic neuropathic pain.
(20) A recent review summarized that high-
frequency rTMS to the motor cortex is able to produce pain relief but that the effect is brief and that research in this area is required.
rTMS has also been used as a probe of neuronal circuits in 
dementia and in attention deﬁ  cit hyperactivity disorder although 
any possible therapeutic role for it in these conditions appears some way off.
Summary
rTMS has an increasing role as a useful investigational tool for probing neuronal circuitry in a variety of neuropsychiatric disorders. However its therapeutic value is at present less certain. 6.2.10.3 transcranial magnetic stimulation

SECTION 6  treatment methods in psychiatry 1266
The anti depressant efﬁ  cacy of rTMS has now been investigated for 
over 15 years and despite initial early enthusiasm there is still not clear evidence for its usefulness as a treatment in depression, reﬂ ected in the recent FDA and NICE decisions. Further research is 
required to identify speciﬁ  c brain regions in speciﬁ  c conditions 
that may be appropriate targets for treatment with rTMS, allowing tailoring of treatments for individual patients. The recent develop-ment of neuronavigational techniques using MRI imaging should aid treatment site localization. Other future research should be directed at establishing optimal rTMS parameters, e.g. the intensity, frequency and number of treatments.
http://www.ists.unibe.ch/ is the homepage of the International Society for 
Transcranial Stimulation. It also provides links to other websites of interest.

George, M.S. and Belmaker, R.H. (eds.) (2007). Transcranial magnetic 
stimulation in clinical psychiatry , p. 289. American Psychiatric 
Publishing. Arlington, V A. Provides a useful summary of the theoretical and practical aspects of TMS research.
Lisanby, S.H. (ed.) (2004). Brain stimulation in psychiatric treatment ,
p. 153. American Psychiatric Publishing, Washington, DC. Reviews 
transcranial magnetic stimulation and also other brain stimulation 
techniques including deep brain stimulation, magnetic seizure therapy and vagus nerve stimulation.
 1. Barker, A.T., Jalinous, R., and Freeston, I.L. (1985). Non-invasive 
magnetic stimulation of human motor cortex. Lancet ,1, 1106–7.
 2. Hallett, M. (2000). Transcranial magnetic stimulation and the human 
brain. Nature ,406,147–50.

 3. Speer, A.M., Kimbrell, T.A., Wassermann, E.M., et al. (2000). Opposite 
effects of high and low frequency rTMS on regional brain activity in depressed patients. Biological Psychiatry ,48, 1133–41.
 4. Strafella, A.P ., Paus, T., Barrett, J., et al. (2001). Repetitive transcranial 
magnetic stimulation of the human prefrontal cortex induces dopamine 
release in the caudate nucleus. The Journal of Neuroscience ,21, RC157.
 5. Wassermann, E.M. (1998). Risk and safety of repetitive transcranial 
magnetic stimulation: report and suggested guidelines from the international workshop on the safety of repetitive transcranial magnetic stimulation, June 5–7, 1996. Electroencephalography and 
Clinical Neurophysiology ,108, 1–16.
 6. Bickford, R.G., Guidi, M., Fortesque, P ., et al. (1987). Magnetic

 6. Bickford, R.G., Guidi, M., Fortesque, P ., et al. (1987). Magnetic 
stimulation of human peripheral nerve and brain: response enhancement by combined magnetoelectrical technique. Neurosurgery ,20, 110–6.
 7. Martin, J.L., Barbanoj, M.J., Schlaepfer, T.E., et al. (2002). Transcranial 
magnetic stimulation for treating depression. Cochrane Database of 
Systematic Reviews ,2, CD003493.
 8. Lisanby, S.H., Gutman, D., Luber, B., et al. (2001). Sham TMS: 
intracerebral measurement of the induced electrical ﬁ  eld and the 
induction of motor-evoked potentials. Biological Psychiatry ,49, 460–3.
 9. Loo, C.K., Mitchell, P .B., McFarquhar, T.F., et al. (2007). A sham-
controlled trial of the efﬁ  cacy and safety of twice-daily rTMS in major 
depression. Psychological Medicine ,37, 341–9.
10. Eranti, S., Mogg, A., Pluck, G., et al. (2007). A randomized, controlled

10. Eranti, S., Mogg, A., Pluck, G., et al. (2007). A randomized, controlled 
trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression. The American Journal of Psychiatry ,164, 73–81.
11. Hoffman, R.E., Boutros, N.N., Berman, R.M., et al. (1999). Transcranial 
magnetic stimulation of left temporoparietal cortex in three patients reporting hallucinated. ‘‘voices’’ Biological Psychiatry ,46, 130–2.12. Aleman, A., Sommer, I.E., and Kahn, R.S. (2007). Efﬁ  cacy of slow 
repetitive transcranial magnetic stimulation in the treatment of 
resistant auditory hallucinations in schizophrenia: a meta-analysis. 
The Journal of Clinical Psychiatry ,68, 416–21.
13. Novak, T., Horacek, J., Mohr, P ., et al. (2006). The double-blind

13. Novak, T., Horacek, J., Mohr, P ., et al. (2006). The double-blind 
sham-controlled study of high-frequency rTMS (20Hz) for negative symptoms in schizophrenia: negative results. Neuroendocrinology 
Letters ,27, 209–13.
14. Mogg, A., Purvis, R., Eranti, S., et al. (2007). Repetitive transcranial 
magnetic stimulation for negative symptoms of schizophrenia: a randomized controlled pilot study. Schizophrenia Research ,93, 221–8.
15. Greenberg, B.D., George, M.S., Martin, J.D., et al. (1997). Effect of 
prefrontal repetitive transcranial magnetic stimulation in obsessive-
compulsive disorder: a preliminary study. The American Journal of 
Psychiatry ,154, 867–9.
16. Martin, J.L., Barbanoj, M.J., Perez, V ., et al. (2003). Transcranial 
magnetic stimulation for the treatment of obsessive-compulsive disorder. Cochrane Database of Systematic Reviews ,
3, CD003387.

17. Prasko, J., Paskova, B., Zalesky, R., et al. (2006). The effect of repetitive 
transcranial magnetic stimulation (rTMS) on symptoms in obsessive-compulsive disorder. A randomized, double blind, sham controlled study. Neuroendocrinology Letters ,27, 327–32.
18. Khedr, E.M., Rothwell, J.C., Shawky, O.A., et al. (2006). Effect of daily 
repetitive transcranial magnetic stimulation on motor performance in 
Parkinson’s disease. Movement Disorders ,12, 2201–5.
19. Rossi, S., De Capua, A., Ulivelli, M., et al. (2007). Effects of repetitive 
transcranial magnetic stimulation on chronic tinnitus. A randomised, cross over, double blind, placebo-controlled study. Journal of Neurology, 
Neurosurgery, and Psychiatry ,78, 857–63.
20. Leo, R.J and Latif, T. (2007). Repetitive transcranial magnetic

20. Leo, R.J and Latif, T. (2007). Repetitive transcranial magnetic 
stimulation (rTMS) in experimentally induced and chronic neuropathic pain: a review. The Journal of Pain ,8, 453–9.
6.2.10.4 Neurosurgery for 
Ablative neurosurgery
Deﬁ nition
Historical deﬁ  nitions of Neurosurgery for Mental Disorder (NMD), 
previously known as ‘psychosurgery’ , have either made distinctions between neurosurgery for psychiatric or ‘psychological’ illness and disorders assumed to have a clearer ‘biological’ origin (e.g. epilepsy, Parkinsons’ disease); or, have emphasized control of behaviour as a therapeutic objective rather than the control of symptoms. A more recent deﬁ  nition, and the one used throughout this chapter is that 
provided by the UK Royal College of Psychiatrists:
(1)

(1)
A surgical procedure for the destruction of brain tissue for the purposes of alleviating speciﬁ  c mental disorders carried out by a stereotactic or other 
method capable of making an accurate placement of the lesion.
Historical overview
The ﬁ  rst attempt at treating psychiatric illness by surgical methods 
is commonly attributed to Gottlieb Burckhardt, a Swiss psychia-trist, who in 1888 performed ‘temporal topectomy’ on six patients who were most probably suffering from schizophrenia. His intention

1267
was to sever the connections between the frontal lobes and the rest 
of the brain. Results were mixed: one patient was reported as improved; two were ‘quieter’; and two showed no change. However, one patient died; another developed epilepsy; and a further had motor weakness. His results were met with a mixture of ridicule and hostility and he never again wrote on the subject.
In 1935, James Fulton and Carlyle Jacobsen operated on the 
frontal lobes of two chimpanzees named Becky and Lucy after ﬁ  rst 
studying their responses to frustration in behavioural experiments. They found their behaviour dramatically changed after the surgery. Becky’s previous agitated responses to frustration became more passive whilst Lucy was much more agitated. At a London meeting in 1935, they presented their ﬁ  ndings to an audience which included 
Egas Moniz, a Portuguese neurologist.
Moniz teamed up with Almeida Lima, a neurosurgeon, and in a

Moniz teamed up with Almeida Lima, a neurosurgeon, and in a 
30-min operation in November 1935, they performed frontal leu-cotomy on their ﬁ  rst patient. The procedure ﬁ  rst involved injecting 
alcohol into the white matter tracts of the frontal lobes, but they later would change to using an instrument of their own design, the leucotome, to extirpate ‘cores’ of tissue. In 1936, they published their report on the outcomes of 20 patients who were probably suffering from depression, panic disorder, and schizophrenia. One-third were better, one-third were worse, and one-third were unchanged.
Shortly after their paper was published, Walter Freeman, 
a US neurologist, wrote an enthusiastic review and quickly secured the collaboration of a neurosurgeon, James Watts. They modiﬁ  ed

the procedure slightly and began practising what Freeman termed bilateral frontal lobotomy. Over the next decade, Freeman became frustrated with the cumbersome requirements of a neurosurgical theatre and team. Adapting a technique first described in the 1930s, Freeman infamously developed the transor-bital lobotomy in 1946. Notorious for the initial use of an ice-pick, the procedure involved forcing a tool (an ‘orbitoclast’) under the upper eyelid and through the base of the skull into the frontal lobes. Also known as the ‘ice-pick lobotomy’ , the relative ease with which the procedure could be performed resulted in the wide-spread adoption of the technique throughout the United States and Europe. However, it was the indiscriminate overuse of such ‘freehand’ procedures and the associated adverse effects that occurred in many patients that led to public and professional antipathy towards neurosurgery for psychiatric illness, which peaked in the late 1950s. The introduction of

adverse effects that occurred in many patients that led to public and professional antipathy towards neurosurgery for psychiatric illness, which peaked in the late 1950s. The introduction of chlorpromazine in 1954 also meant that for the ﬁ  rst time there was a non-surgical

treatment for schizophrenia.
Despite a reduction in the use of neurosurgery for mental disorder 
in the late 1950s and early 1960s, the development of stereotactic techniques (which had been demonstrated in 1908 by Horsley and Clarke and adapted for human use in 1947 by Spiegel and Wycis) meant that greater accuracy and greater consistency in neurosurgery could deliver better outcomes in selected patients. Procedures became more selectively and reliably targeted and lesions became 
more discrete.
All NMD procedures have targeted one or more of three main 
regions: (i) fronto-limbic connections within the orbital or cingulate cortices; (ii) subcortical limbic circuitry; and (iii) limbic cortex, including the amygdala and cingulate cortex.Four ‘modern’ stereotactic procedures have been described with

only two remaining in regular usage in the Western World. Anterior capsulotomy is still performed in Cardiff (UK), Spain, Belgium, and Scandinavia, whilst anterior cingulotomy is the procedure of choice in Dundee (UK), Poland, South Korea, and North America.
(a) Subcaudate tractotomy (SST)
Developed in the United Kingdom by Geoffrey Knight in 1965, lesions were originally created using radioactive Yttrium
90 rods. 
SST targets the white matter tracts of the ‘substantia innominata’ connecting the orbital cortex to limbic regions, and probably involved lesioning the nucleus accumbens.
(b) Anterior capsulotomy (ACAPS)

Described by Jean Talairach in 1949 and further developed by Lars Leksell for the treatment of chronic pain, ACAPS places lesions in the anterior limb of the internal capsule—a large white matter bundle connecting the frontal cortex with the thalamus and limbic structures. Lesions are generated using focused gamma radiation (gammacapsulotomy) or thermal damage (thermocapsulotomy). (See ﬁ  gure 6.2.10.4.1 for typical ACAPS lesions.)
(c) Anterior cingulotomy (ACING)
The cingulate gyrus was ﬁ  rst proposed as a target by John Fulton in 
the late 1940s. Hugh Cairns, an English neurosurgeon and a friend of Fulton’s, performed ‘cingulectomy’ in 1948. The less destructive ‘cingulotomy’ was ﬁ  rst performed by Eldon Foltz and Lowell White 
in 1962 for the treatment of pain. (See ﬁ  gure 6.2.10.4.2 for typical 
ACING lesions.)
(d) Limbic leucotomy

First developed by Desmond Kelly in 1973, it represented a combi-nation of cingulotomy and subcaudate tractotomy lesions.
During the 1960s and 1970s, a variety of other operations were explored as treatments for hypersexuality, aggression, and crimi nality. 
These included hypothalamotomy and amygdalotomy. Reports of outcomes from such interventions were often favourable, but interpretation has been complicated by issues of diagnosis, patient selection, and assessment. Such clinical presentations are not considered appropriate indications for surgery today.
Three main indications exist for modern NMD: obsessive-

compulsive disorder (OCD); anxiety disorders; and major depres-sion. Only individuals who have experienced chronic, disabling symptoms that have failed to respond after the diligent pursuit of available treatments (pharmacological and psychological) should be considered for ablative neurosurgery.
There are few absolute contraindications to NMD. There is no 
evidence to support the use of NMD as a treatment for eating 
disorders, schizophrenia, or personality disorders. However, where these exist as signiﬁ  cant comorbid conditions alongside depression 
or OCD, these do not represent absolute contraindications and careful consideration is required.
Ethical considerations
One of the most persistent concerns for the public and for health professionals is that NMD is used to tr eat patients in the absence of

One of the most persistent concerns for the public and for health professionals is that NMD is used to tr eat patients in the absence of 
informed consent. Although the absence of informed consent was likely to be an issue for early procedures, to the best of our knowledge, 6.2.10.4 neurosurgery for psychiatric disorders

SECTION 6  treatment methods in psychiatry 1268
all contemporary centres performing NMD today insist upon the 
patient’s ability to give informed consent. In Scotland, the Mental Welfare Commission must authorize any proposed NMD as being in the patient’s best interests and must conﬁ  rm that the patient is 
capable of providing informed consent. In England and Wales, the Mental Health Act Commission has a duty to set-up multi-disci-plinary panels to authorize NMD for consenting patients under Section 57 of the Mental Health Act, 1983. Similarly, in most other countries where the procedure is available, the procedure can only go ahead with the approval of an independent review board.
Criteria for NMD
General criteria for suitability show little variation between centres. Key inclusion and exclusion criteria for NMD in Dundee are shown below in Table 6.2.10.4.1.
Outcomes from NMD
Whilst placebo-controlled trials are considered the ideal assessment

Whilst placebo-controlled trials are considered the ideal assessment 
for intervention trials, they have frequently been described as unethical in the case of NMD. Despite this, there have been three isolated double-blind trials, involving a total of 6 patients. Despite suggestions of non-response in all cases, follow-up was brief and there is inadequate detail to make informed judgements of outcome.
(a) Combined outcomes for different procedures
Comparisons across studies are of limited value due to differences in procedure, patient characteristics, and the use of different rating scales. However, Spangler et al.
2 reviewed outcomes from different 
procedures and for different indications, deﬁ  ning a positive out-
come as being a score of 1 or 2 on the Clinical Global Impression (Improvement) scale.
(2) Positive outcome rates were: ACAPS

(2) Positive outcome rates were: ACAPS 
(67 per cent); ACING (61 per cent); SST (37 per cent); and limbic leucotomy (67 per cent). The most effective procedures for affective disorder and OCD (respectively) were limbic leucotomy followed by ACING. The least effective procedure for both disorders (and overall) was SST.(b) Anxiety disorders
The crude rate of improvement following NMD (all procedures) for anxiety disorders ( n = 290) is 77 per cent.
(1) More recent reports 
of ACAPS would support a claim to effectiveness but this may be at the expense of signiﬁ  cant adverse effects (apathy and dysexecutive 
symptoms).
(c) Obsessive-compulsive disorder

The combined rate of ‘Completely Improved’ or ‘Improved’ outcomes following SST is 52 per cent. More recent studies involv-ing ACAPS or ACING report improvements on the Y ale-Brown Obsessive-Compulsive scale (Y-BOCS) in the region of 30 per cent. Despite this relatively low ﬁ  gure, approximately 85 per cent of 
patients ( n = 478) will have a marked or lesser improvement 
following NMD for OCD.
(1)
(d) Depression
There is only one report of outcomes from ACAPS for depression. Herner (1961) described outcomes for 19 patients with a ‘depressive state’ .
(3) Outcomes included: ‘permanent improvement’ 
(74 per cent); unchanged (5 per cent); and worse (5 per cent). In all 75 per cent experienced permanent side effects.
Spangler et al . (1996) reported that 53 per cent of those with

Spangler et al . (1996) reported that 53 per cent of those with 
affective disorder ( n = 10) responded to ACING, with a 60 per cent 
response rate in unipolar depression.
(2) Dougherty et al . (2003) 
reported a mean reduction in Beck Depression Inventory (BDI) 
score of 33 per cent in 13 patients following ACING.(4) With regards 
to limbic leucotomy, there are few studies looking at outcomes 
solely in depression but Mitchell-Heggs (1976) reported that 7 of 
9 patients with depression improved after surgery.(5)
(e) Bipolar disorder
There are only two reports of NMD for bipolar disorder, both following SST.
(6, 7) Each involved small numbers ( n = 9 ) but 
described improvements in cycle frequency with a greater effect on manic episodes than depression. Improved drug responsiveness was also alleged.

The mechanism of action of NMD is unknown, but almost all neurosurgical procedures involve lesioning white matter tracts connecting the prefrontal cortex with the thalamus, cingulate gyrus, and areas of the limbic system such as the amygdala and hippocampus. Neuroimaging studies have suggested that this 
circuitry is dysfunctional in depression and interrupting 
parts of these circuits may rectify emotional and cognitive process-ing within these brain areas. In the case of OCD, there is compel-ling evidence that symptoms arise from functional circuits connecting the frontal cortex, thalamus, and basal ganglia and that lesioning parts of this circuit may serve to eradicate many of the symptoms.
(a) General adverse effects

Transient adverse effects such as headache are relatively common and tend to resolve in the ﬁ  rst week after surgery. Post-operative 
confusion can occur in 3–10 per cent of patients with higher rates following SST. Incontinence is relatively uncommon with modern procedures, but the reported rates are: 1.1 per cent after SST; Table 6.2.10.4.1  Inclusion and exclusion criteria for NMD
Inclusion criteria Exclusion criteria
1. Age ≥20 years 1. Age <20 years
2.  Legal status : both formal and 
informal patients can be considered2.  Failure to fulﬁ  l ICD-10 criteria for 
a suitable indication
3.  ICD-10 diagnosis of : severe depressive 
episode; recurrent depressive disorder, 
current episode moderate to severe; bipolar affective disorder, current 
episode severe depression3.  Primary diagnosis of : substance 
misuse; organic brain syndrome; 
adult personality disorder; pervasive developmental 
disorder
4.  Duration of episode of illness :

disorder
4.  Duration of episode of illness : 
minimum of 3 years, with at least 2 years of unremitting symptoms 
despite active treatment. Only in 
exceptional circumstances would a duration<5 years be considered4.  Absence of evidence of an 
adequate therapeutic trial of psychological treatment
5.  Consent : the patient must be 
capable of providing sustained, 
informed consent5.  Absence of evidence of 
extensive trials of adequate 
pharmacological treatment

1269
5.5 per cent after ACING; and 9.5 per cent with limbic leucotomy. 
Apathy has been reported to occur in up to 24 per cent of patients following limbic leucotomy, but not all studies report its occurrence and this is likely to be a relatively high estimate. The incidence of weight gain varies greatly: 6.2 per cent after SST; 65.5 per cent after ACAPS; and 5.5–21.4 per cent after ACING. Similarly, there is wide variation in the reported rates of seizures: 1.6–3.3 per cent after SST; 0–7.7 per cent after ACAPS; 1–9 per cent after ACING; and 14.2 per cent after limbic leucotomy. Finally, suicide rates range from 1 per cent after SST to 12 per cent after ACING but these rates may reﬂ  ect differing severities of illness.
(b) Effects on personality
It is certainly the case that early procedures such as leucotomy had

It is certainly the case that early procedures such as leucotomy had 
marked effects on the personality and behaviour of large numbers of patients. However, with the advent of stereotactic procedures and more focused lesions, the effects on personality appear to be mild, sometimes even absent. It is acknowledged, however, that it is difﬁ  cult to make robust appraisals of personality without 
assessment tools designed for such a purpose and in the context of symptom reduction in chronic illnesses.
Most published studies have reported normalization of 
personality traits following modern procedures such as ACING and ACAPS. In addition, there is a trend towards reductions in neuroticism and increases in extraversion. There are some recent reports of adverse effects on executive function following 
ACAPS for anxiety disorders
(8) but many such studies lack preop-
erative assessments of personality making conclusions difﬁ  cult 
to draw.

to draw.
(c) Effects on neuropsychological function
As with personality changes, the detrimental effects of earlier procedures upon neuropsychological functioning were probably signiﬁ  cant. However, the majority of studies reporting neuropsy-
chological outcomes from ACAPS, ACING, and limbic leucotomy from the early 1970s onwards report either no deterioration on general measures (such as IQ, attention, memory) post-operatively or, more frequently, improvement. It is likely that improvements in performance are mediated through symptom reduction.
Vagus nerve stimulation (VNS)
Overview
The vagus nerve is the longest of the 12 cranial nerves and 80 per cent of its ﬁ  bres are sensory afferents. These ﬁ  bres terminate in the 
nucleus tractus solitarius, sending ascending ﬁ  bres to the forebrain

nucleus tractus solitarius, sending ascending ﬁ  bres to the forebrain 
via the locus coeruleus and parabrachial nucleus. The vagus nerve, 
therefore, provides an access route to modify information which is 
processed in brain regions involved in mood regulation.
VNS involves the subcutaneous implantation of a programmable 
pulse generator in a location similar to a cardiac pacemaker. 
Electrodes connect the generator to the left cervical portion of the 
vagus nerve. Stimulation is delivered in an intermittent pattern (typically 30 s every 5 min) but parameters are changed using a palmtop computer and a programming wand held over the pulse 
generator.
VNS was ﬁ  rst used to treat epilepsy in 1988 and became available 
for the treatment of refractory partial seizures in 1994. The ﬁ  rst 
trials in depression began in 1998.Outcomes in depression
There are a number of short, open trials of VNS which typically report a 3-month response rate ( ≥50 per cent reduction in the 24-item

There are a number of short, open trials of VNS which typically report a 3-month response rate ( ≥50 per cent reduction in the 24-item 
Hamilton Rating scale for Depression; HRSD
24) of 30–40 per cent, 
and a remission rate (HRSD24≤ 9) of approximately 15 per cent.
Larger, 12-month trials have demonstrated 12-month response 
rates of 27.2–46 per cent and remission rates of 15.8–29 per cent.(9,10)
In a 12-month controlled comparison of VNS versus Treatment-As-Usual (TAU), George et al.
(11) reported response rates of 27 per 
cent for VNS + TAU versus 13 per cent for TAU. Such improve-ments appear to be maintained at 2 years, with response rates of 42 per cent and remission rates of 22 per cent.
(12) In the only 
randomized, controlled trial of VNS, Rush et al .(13) reported 10-
week response rates on the HRSD24 of 15.2 per cent in the VNS 
group versus 10.0 per cent in the placebo group, changes which were non-signiﬁ  cant.

(13) Despite positive results in uncontrolled 
trials, deﬁ  nitive evidence of efﬁ  cacy remains elusive.
Most adverse effects are related to stimulation, and in most people 
they are fairly mild and improve over time. Many can be managed by altering the stimulation parameters. In the initial stages, com-mon effects are: hoarse voice (53 per cent); headache (23 per cent); neck pain (17 per cent); cough (13 per cent); and dyspnoea (17 per cent). At 12-months, the only adverse effect to persist at rates higher than 10 per cent is hoarse voice (21 per cent).
(9)
Deep brain stimulation (DBS)
Overview
As with VNS, DBS has evolved from a treatment for neurological disorders to a putative intervention for psychiatric illness. The most 
Fig. 6.2.10.4.1 Typical locations of anterior capsulotomy lesions superimposed

Fig. 6.2.10.4.1 Typical locations of anterior capsulotomy lesions superimposed 
upon normalized T1 MRI scan.Lesions not to scale.
6.2.10.4 neurosurgery for psychiatric disorders

SECTION 6  treatment methods in psychiatry 1270
effective targets for OCD and depression have yet to be determined 
but a number of possible locations for stimulation exist. However, DBS should be considered as an experimental treatment for both disorders.
The procedure involves the bilateral implantation of electrodes 
using stereotactic guidance with post-operative conﬁ  rmation of 
location using MR scanning. The electrodes are connected to a generator typically implanted in the abdomen. Following surgery, the stimulation settings are programmed using immediate/short-term changes in symptoms as a guide.
DBS for obsessive-compulsive disorder
The most common target for DBS for OCD, thus far, has been ventral portion of the anterior limb of the internal capsule, the same site as ablative anterior capsulotomy. In a double-blind cross-over trial of anterior capsular stimulation in four patients Nuttin et al . (2003) reported reductions in symptoms of 36.8 per cent

which were maintained after 21 months. In a small case series of four patients Abelson et al.
(14) described marked improvements in 
one patient, with a lesser improvement in another. Greenberg et al.
(2006) reported responses ( ≥35 per cent reduction in Y-BOCS 
score) in 4 out of 8 patients with DBS in the internal capsule.
Other proposed targets include the nucleus accumbens and the 
ventral caudate nucleus, but all targets may involve stimulation of a common anatomical area.
DBS for depression
In the only published report of DBS for depression, Mayberg et al.
15 stimulated the white matter tracts of the subgenual cingu-
late gyrus in six patients. Four patients were responders whilst two showed no change. Randomized on-off-on-off trials conﬁ  rmed 
a stimulation-related improvement which was associated with a reduction in local cerebral blood ﬂ  ow in the subgenual cingulate 
and dorsolateral prefrontal cortex.

Adverse effects that have been reported include: throbbing or buzzing sensations; nausea; and jaw tingling. A number of reports have described problems with battery life with the stimulators being replaced every 5 to 12 months. Battery failure has often been associated with a recurrence of symptoms over a few days which has been associated with marked depressive symptomatology and suicidal ideation. One study has reported a suicide, but commented that this was unrelated to stimulation. Numbers of reported cases are too small to determine if this is indeed the case.

Despite its chequered past, modern NMD bears little similarity to historical freehand procedures. Advances in neuroimaging mean that anatomical substrates for depression and OCD are being elucidated. Ablative procedures such as ACAPS and ACING are unlikely to undergo randomized controlled trials but prospective clinical audit suggests that such procedures may offer improvement to selected patients with treatment-refractory depression and OCD. 
Interventions such as VNS and DBS offer the possibility of double-
blind testing but as yet there is insufﬁ  cient evidence to suggest that 
such procedures offer greater effectiveness.
Freeman, C., Crossley, D., and Eccleston, D. (2000). Neurosurgery for mental 
disorder. Report from the Neurosurgery Working Group of the Royal College of Psychiatrists. Royal College of Psychiatrists, London.
Binder, D.K. and Iskandar, B.J. (2000). Modern neurosurgery for psychiatric 
disorders. Neurosurgery ,47, 9–21.

Feldman, R.P ., Alterman, R.L., and Goodrich, J.T. (2001). Contemporary 
psychosurgery and a look to the future. Journal of Neurosurgery ,
95, 944–56.
George, M.S., Rush, A.J., Sackeim, H.A., et al.  (2003). Vagus nerve 
stimulation (VNS): utility in neuropsychiatric disorders. International 
Journal of Neuropsychopharmacology ,6, 73–83.
Malone, D.A., Greenberg, B.D., and Rezai, A.R. (2004). The use of deep 
brain stimulation in psychiatric disorders. Clinical Neuroscience 
Research ,4, 107–12.
1. Freeman, C., Crossley, D., and Eccleston, D. (2000). Neurosurgery for 
mental disorder. Report from the Neurosurgery Working Group of the Royal College of Psychiatrists . Royal College of Psychiatrists, London.
2. Spangler, W.J., Cosgrove, G.R., Ballantine, H.T. Jr., et al. (1996).

2. Spangler, W.J., Cosgrove, G.R., Ballantine, H.T. Jr., et al. (1996). 
Magnetic resonance image-guided stereotactic cingulotomy for intractable psychiatric disease. Neurosurgery ,38, 1071–6.
3. Herner, T. (1961). Treatment of mental disorders with frontal stereotaxic 
thermo-lesions: a follow-up study of 116 cases. Acta Psychiatrica 
Scandinavica ,36(Suppl. 158), 1–140.
4. Dougherty, D.D., Weiss, A.P ., Cosgrove, G.R., et al. (2003). Cerebral 
metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression. Journal of Neurosurgery ,
99, 1010–7.
5. Mitchell-Heggs, N., Kelly, D., and Richardson, A. (1976). Stereotactic 
limbic leucotomy—a follow-up at 16 Months. The British Journal of 
Psychiatry ,128, 226–40.Fig. 6.2.10.4.2 Typical locations of anterior cingulotomy lesions superimposed 
upon normalized T1 MRI scan. Lesions not to scale.

1271
 6. Lovett, L.M. and Shaw, D.M. (1987). Outcome in bipolar affective 
disorder after stereotactic tractotomy. The British Journal of Psychiatry ,
151, 113–16.
 7. Poynton, A., Bridges, P .K., and Bartlett, J.R. (1988). Resistant bipolar 
affective disorder treated by stereotactic subcaudate tractotomy. The
British Journal of Psychiatry ,152, 354–8.
 8. Rück, C., Andreewitch, S., Flyckt, K., et al. (2003). Capsulotomy for 
refractory anxiety disorders: long-term follow-up of 26 patients. The
American Journal of Psychiatry ,160, 513–21.
 9. Marangell, L.B., Rush, A.J., George, M.S., et al. (2002). Vagus nerve 
stimulation (VNS) for major depressive episodes: one year outcomes. 
Biological Psychiatry ,51, 280–7.
10. Rush, A.J., Sackeim, H.A., Marangell, L.B., et al. (2005). Effects of 12 
months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biological Psychiatry ,58, 355–63.11. George, M.S., Rush, A.J., Marangell, L.B., et al. (2005). A one-year

months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biological Psychiatry ,58, 355–63.11. George, M.S., Rush, A.J., Marangell, L.B., et al. (2005). A one-year 
comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biological Psychiatry ,58, 364–73.
12. Nahas, Z., Marangell, L.B., Husain, M.M., et al. (2005). Two-year 
outcome of vagus nerve stimulation (VNS) for treatment of major 
depressive episodes. The Journal of Clinical Psychiatry ,66,
1097–104.
13. Rush, A.J., Marangell, L.B., Sackeim, H.A., et al. (2005). Vagus nerve 
stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biological Psychiatry ,58, 347–54.
14. Abelson, J.L., Curtis, G.C., Sagher, O., et al. (2005). Deep brain 
stimulation for refractory obsessive-compulsive disorder. Biological Psychiatry ,57, 510–6.
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stimulation for treatment-resistant depression. Neuron ,45, 651–60.6.2.10.4 neurosurgery for psychiatric disorders

Contents
 6.3.1 Counselling
 6.3.2 Cognitive behaviour therapy
  6.3.2.1  Cognitive behaviour therapy for 
  6.3.2.2  Cognitive behaviour therapy for 
eating disorders
    Zafra Cooper, Rebecca Murphy, and 
  6.3.2.3  Cognitive behaviour therapy 
for depressive disorders
  6.3.2.4 Cognitive behaviour therapy for schizophrenia
 6.3.3 Interpersonal psychotherapy for 
depression and other disorders
 6.3.4 Brief individual psychodynamic psychotherapy
 6.3.5 Psychoanalysis and other long-term 
dynamic psychotherapies
 6.3.6 Group methods in adult psychiatry
 6.3.7 Psychotherapy with couples
 6.3.8 Family therapy in the adult psychiatric setting

 6.3.9 Therapeutic communities
David Kennard and Rex Haigh6.3.1 Counselling
People seek counselling for many reasons. Sometimes those who 
have had no previous need for mental health services are literally stopped in their tracks by life events—illness, family breakdown, intolerable stresses. People with long-term difﬁ  culties may turn to 
counselling when they feel the statutory services are not able to meet their needs, or as an adjunct to health care provision. With greater social mobility and the separation of family members, counselling increasingly provides the care and support previously offered within local communities. The provision and acceptability of counselling is on the increase. Counselling is possibly the most commonly delivered form of psychological therapy
(1, 2) and the

(1, 2) and the 
British Association for Counsellors and Psychotherapists have over 30 000 members, with equivalent numbers in other countries. Professional training programmes in counselling have mush-roomed in response to demand. Counsellors are found in many statutory and voluntary settings—mental health, primary care and medical settings, workplaces, drug and alcohol services, voluntary and charitable organizations, trauma services, and educational settings—as well as in private practice.
But what exactly is counselling? What do counsellors do? Is 
counselling the same as psychotherapy? And, is it an effective form of treatment? Although counselling is a major growth area within mental health, it can be difﬁ  cult for consumers and purchasers of 
counselling services to know what kind of counselling and counsel-
lor to use, with lack of clarity about what works for whom. There

lor to use, with lack of clarity about what works for whom. There 
are many different models of counselling, types of counsellor and many different training courses. It is difﬁ  cult to make clear distinc-
tions between counselling and psychotherapy. Much of the work of counsellors has not historically been amenable to standard meth-ods of evaluation, and research is relatively new. Currently there is no statutory regulation for the term ‘counsellor’ , which means that people are able to practise as counsellors without registration or accreditation. By deﬁ  nition, people who seek counselling are likely 
to be vulnerable, and the issue of public protection is paramount.6.3

1273
The aim of this chapter is to clarify these issues and examine the 
place of counselling in psychiatry. The chapter begins by looking at the deﬁ  nition of counselling, and how counselling is both similar 
to, and distinct from, psychotherapy. The chapter goes on to look at the key features of counselling, and different models of counselling. Although counselling can and is used for many psychological dif-ﬁ culties, the chapter selects speciﬁ  c problems where there is evi-
dence that it is an effective intervention: mild to moderate depres-sion, adjustment difﬁ  culties, bereavement, trauma, and relationship

dence that it is an effective intervention: mild to moderate depres-sion, adjustment difﬁ  culties, bereavement, trauma, and relationship 
problems. I then consider counselling in different settings, again selecting a few which illustrate the work of counsellors—primary care, mental health settings, student counselling, and the work-place—looking at the way counselling can be adapted according to the needs of the service. The chapter concludes by looking at issues of training, quality, and standards, commenting on the need for the control of an ever-developing profession without loss of the grow-ing availability of effective counselling services to those in need.
Deﬁ ning counselling
No single deﬁ  nition of either counselling or psychotherapy exists 
in spite of many attempts in Britain, North America, and elsewhere to arrive at one.
(3) Currently, neither the British Association

(3) Currently, neither the British Association 
of Counselling and Psychotherapy (BACP) nor the American Counseling Association has either proprietary rights of the terms or even ofﬁ  cial deﬁ  nitions, although, as discussed below, the move 
towards statutory regulation for counselling and psychotherapy may ensure greater clarity for practitioners and consumers.
At its broadest, counselling is conceptualized as a way of helping 
or assisting others to make their own adjustment and decisions in the face of life problems. Counselling aims to offer a safe relation-ship within which the individual can explore personal difﬁ  culties 
and, through developing a deeper understanding of themselves, move towards change. The Department of Health deﬁ  nes counsel-
ling as . . . a form of psychological therapy that gives individuals an 
opportunity to explore, discover, and clarify ways of living more

opportunity to explore, discover, and clarify ways of living more 
resourcefully, with a greater sense of well being. Counselling may be 
concerned with addressing and resolving speciﬁ  c problems, making decisions, coping with crises, working through conﬂ  ict, or improving 
relationships with others .
(4)
In contrast with other forms of psychological therapy, where 
the focus may be on treating speciﬁ  c problems, many counselling 
models give equal if not more weight to the process  of change. The 
journey through which a client goes—to greater understanding, awareness, and resolution—is as important as the outcome. Counsellors practise within all therapeutic approaches, strongly inﬂ uenced by humanistic, experiential, and psychodynamic prin-

ciples. They tend not to link their work to diagnostic categories, preferring to see each client as an individual, and using an approach matching the client’s needs rather than diagnosis. Counsellors may define themselves by the model they practise—for example, humanistic or psychodynamic—and/or by the type of problems they work with, such as bereavement or relationship counsellors.
Counselling may also be deﬁ  ned in terms of key elements  and 
goals ,
(5) as shown in Table 6.3.1.1. Again, the key elements and goals 
illustrate the variation within counselling. For example, what is meant by counselling ranges from providing a safe arena for people to gain understanding and insight, to offering more direction and guidance leading to decision-making and problem-solving.Counselling and psychotherapy
Much of the above can also be applied to psychotherapy and parts of this chapter do indeed overlap signiﬁ  cantly with psychotherapy.

Much of the above can also be applied to psychotherapy and parts of this chapter do indeed overlap signiﬁ  cantly with psychotherapy. 
There may well be variation between countries in what is deﬁ  ned as 
counselling or psychotherapy. Counselling and psychotherapy each have distinct features including different historical roots. Psychotherapy  arose from the seminal works of Freud in the late 
nineteenth and twentieth centuries, and in the past, psychothera-pists tended to offer a long-term psychodynamic approach. Now, however, psychotherapy also includes interpersonal, humanistic, and cognitive models. In the United States, counselling  was origi-
nally linked with vocational guidance, personnel management, and the workplace,
(5) and as such was much more advisory and direc-

tive than the analytic processes of psychotherapy. Carl Rogers, the founder of non-directive counselling in the 1940s, initiated the movement away from practical guidance and problem-solving towards collaborative and person-centred models, forming the basis of counselling today.
Differences between psychotherapy and counselling tend to 
relate more to the individual psychotherapist’s or counsellor’s training and interests and to the setting in which they work, rather than to any intrinsic difference in the two activities. In medical and mental health settings, psychotherapists are more likely to work with patients with severe psychological disorders, offering long-term therapy, whereas counsellors may concentrate on difﬁ  culties 
amenable to short-term work—mild to moderate psychological 
disorders, relationship difﬁ  culties, or bereavement. Counsellors

disorders, relationship difﬁ  culties, or bereavement. Counsellors 
who work for voluntary agencies or in educational settings such as schools and colleges usually concentrate more on the ‘everyday’ problems and difﬁ  culties of life than on severe psychological disor-
ders, although agencies such as MIND, Alcoholics Anonymous, or Table 6.3.1.1  The key elements and goals of counselling 
(Reproduced from Feltham, C. What are counselling and 
psychotherapy? In The Sage Handbook of Counselling and 
Psychotherapy, (eds. C. Feltham and I. Horton), pp. 3–10, copyright 2006, Sage Publications.)
The key elements of counselling The goals of counselling
◆ Listening and talking methods ◆ Support, psycho-education 
 of addressing psychological  and guidance
 and psychosomatic problems ◆ Insight and understanding
 and change ◆ Self actualization and 
◆ An unstructured and non-directive  personality change

of addressing psychological  and guidance
 form of therapy, using the ◆ Adjustment, symptom 
 therapeutic relationship as an  reduction and ‘cure’ active ingredient in promoting 
◆ Problem-solving and 
 change  decision-making
◆ Counselling operates largely ◆ Crisis intervention and 
 without medication or other  management physical interventions
◆ Risk management (e.g. genetic 
◆ Counselling may be concerned  counselling)
 not only with mental health but  with social, spiritual, philosophical and other aspects of living
◆  Professional forms of counselling are 
based on formal training, accreditation 
and on-going supervision and 
professional development6.3.1 counselling

SECTION 6  treatment methods in psychiatry 1274
Narcotics Anonymous offer counselling to people with serious 
mental illnesses. In private practice, however, a counsellor’s work will overlap with that of a psychotherapist.
In a pragmatic vein, Feltham states that practitioners and the 
public stand to gain much more from the assumption of commonality than from spurious or inﬁ  nitesimal distinctions . . . little is to be gained 
practically from further controversy about professional titles and distinctions .
(5) In 2000, the British Association for Counselling 
lent weight to greater rapprochement by becoming the British Association for Counselling and Psychotherapy. On a practical level, it is interesting that many recipients of ‘talking therapies’ other than counselling, such as psychotherapies, cognitive-behaviour therapy and problem-focused discussions with GPs, psychiatrists, or nurses, say that they have received counselling ,

reinforcing Feltham’s plea that the issue of deﬁ  nition and distinc-
tion is academic rather than of practical value.
Counselling skills and counselling practice
Counselling skills  are integral to the practice of psychiatry and all the 
‘helping professions’ , as basic ingredients of effective interviewing, accurate history-taking, diagnosis, and treatment-planning.
(6) The 
skills of listening, summarizing, reﬂ  ecting, checking, understand-
ing, gaining rapport, and communicating enable other people to feel understood. They are essential for engagement and eliciting information, especially when the person is afraid, in pain, or mis-trustful. The health worker’s counselling skills may inﬂ  uence the 
patient’s collaboration with an active participation in treatment, and thereby the outcome of a wide range of medical and even surgi-cal treatments. Many helping and health professionals such as social workers, occupational therapists, probation ofﬁ  cers, and speech

and communication therapists use counselling skills as an integral part of their work but would not be seen as primarily counsellors.
In contrast, counsellors as professionals , who use counselling as a 
speciﬁ  c intervention, work in many areas of mental health practice 
alongside psychotherapists, clinical and counselling psychologists, psychiatrists, psychiatric nurses, and social workers.
(7) For profes-
sional counsellors, counselling skills are central to their work.
Counselling as a speciﬁ  c planned intervention in psychiatry can 
be differentiated into two broad and overlapping categories, deﬁ  ned 
by aims into decision-making  and treatment :
◆ Decision-making  is an important ingredient in many forms of 
therapeutic counselling but, conversely, some forms of decision-oriented counselling (e.g. genetic counselling) embody no explicit therapeutic intention.
◆Counselling as a primary treatment  for problems is used in the

◆Counselling as a primary treatment  for problems is used in the 
management of a range of conditions as an adjunct to other interventions including medication, as an integral component of a multimodal treatment method (e.g. crisis intervention), or as a speciﬁ  c treatment in its own right (e.g. for postnatal 
Counselling psychology
As well as professional counsellors, counselling psychologists have a particular role to play within counselling provision in mental health. The area of counselling psychology, now developing in the United Kingdom in line with other parts of the world, is a distinctive profession within applied psychology, which aims to foster the psy-chological development of the individual and help people develop more effective and fulﬁ  lled lives. It is based on the fundamental tenets of counselling, but in addition aims to integrate the applica-
tion of psychological theory and research into its practice.
(8)

(8)
Counselling psychologists use a variety of therapeutic models, including person-centred, psychodynamic, and cognitive. Although the training of counsellors can be varied, as discussed below, counselling psychologists undergo standardized post-graduate doctorate training leading to chartered status within the British Psychological Society, or equivalent in other countries.
Is counselling an effective method of 
treatment?
Despite the proliferation of counsellors in many areas of medicine 
and psychiatry, counselling has tended to lag behind medicine and other health care professions in engaging in and promoting research to establish its effectiveness and efﬁ  cacy.
(9) The nature of counsel-
ling can mean that standard methods such as RCTs are not appro-priate means of evaluation, whereas qualitative research methodology is better able to assess meaningful changes.
(10) However, counsel-

ling as a profession is now engaging in better quality research, concentrating on outcomes in routine practice as well as qualitative analysis. New practice-based methods of evaluation, such as CORE (Clinical Outcomes in Routine Evaluation), and the aggregation of data across UK NHS counselling services can lead to national benchmarks. Methods of case-study research, and the development of measures of the client’s perspective on psychological distress, PSYCHLOPS,
(11) enable more client-focused research. Such 
emphasis on evidence-based practice will lead to more careful targeting of speciﬁ  c counselling approaches to speciﬁ  c problems,
(3)
clearer information for the public and will improve counselling’s 
parity with other health care professions.

(3)
Currently, counselling has an image that it is more appropriate 
for people with mild to moderate difﬁ  culties. The Department of 
Health(4) recommends that counselling should not be the main 
intervention for people with severe and complex mental health problems or personality disorders. Patients who are adjusting to life events, illnesses, disabilities, or losses may beneﬁ  t from brief 
therapies such as counselling. However, counsellors such as those in primary care and the voluntary sector are already offering an important and valued service. Although people with more serious and enduring mental health difﬁ  culties require primarily psychiat-
ric and pharmacological intervention, offering emotional support, advice, and problem-solving can form an important, although under-researched, part of their care.
The core conditions of counselling and the

The core conditions of counselling and the 
therapeutic relationship
Counselling depends primarily on the interaction between the 
counsellor and client, what goes on in that interaction and the qualities of both client and counsellor. Carl Rogers’
(12) deﬁ nition 
of the conditions necessary for therapeutic change was a radical departure from traditional psychotherapeutic practice, in empha-sizing the qualities  and attitudes  of the counsellor rather than spec-
ifying what the counsellor must do. His work led to the following as 
necessary  and sufﬁ cient  conditions for therapeutic change:
◆The client is in a state of incongruence , being vulnerable or anxi ous.
◆The therapist is congruent  and genuine  in the relationship with 
the client.

1275
◆The therapist experiences unconditional positive regard  for the 
client.
◆The therapist experiences an empathic understanding  of the 
client’s frame of reference or way of seeing things.
◆The therapist feels non-possessive warmth  towards the client.
◆The client perceives  the therapist’s unconditional positive regard 
and empathic understanding.
These core conditions have been used and developed in many 
models of counselling and therapy; even therapies traditionally seen as more technical have always maintained their importance.
(13)
Empathy , for example, a core condition which is central to all good 
therapeutic relationships, enables clients to know that they are heard and understood. At its simplest, empathy is a simple restate-ment of someone else’s words. At its richest, it involves ... a fearless

exploration of another’s inner world, a sensing of meanings unspoken, a compassionate naming of pain ... the fullest empathy does not censor or discriminate. It sees the world as the other person sees it .
(14)
While Rogers took the view that such core conditions are both 
necessary and sufﬁ  cient for therapeutic change to occur, other 
models of counselling have deﬁ  ned such conditions as necessary 
but not in themselves sufﬁ  cient for change. However, the core con-
ditions remain the bedrock upon which counselling is practised.
The therapeutic relationship
Across very diverse treatments, including cognitive and psycho-pharmacological,
(15) measures of the strength of the relationship, 
or alliance, have been the strongest and most consistent process correlates of treatment outcome.
(3,16) Clients who have strong alli-
ances with their therapists tend to have better outcomes.
Although recognized as an essential component of change, dif-

ferent models have different conceptual and practical approaches to the relationship. Three examples illustrate the differences:
◆Person-centred models take a here-and-now perspective, looking at the immediate interaction between client and counsellor. The client’s perception of the therapist’s empathy, unconditional positive regard, and congruence enables therapeutic change.
◆Cognitive models regard the relationship as necessary but not sufﬁ cient for therapeutic change. The relationship is primarily 
collaborative, with an active, working bond formed between client and counsellor to facilitate the tasks of therapy.

◆Psychodynamic models distinguish the real relationship between client and counsellor, and the transference relationship, consist-ing of both client transference and therapist counter transference. The working alliance therefore is only partly based in reality, also containing aspects of both parties’ histories.
Counselling methods and techniques

There have always been many approaches to counselling and psychotherapy, and this diversity grew into a veritable ‘multiverse’ during which some authors estimated that there were over 400 brand therapies in existence. There are also different settings and agencies which offer counselling—clinics, institutes, health centres, or voluntary bodies, each with its own particular features. Within each model and setting, there are different formats of coun-selling including self-help materials on CD-rom and the Internet, as well as individual, couple, group, family, and organizational. Such a range can be confusing to potential clients and 
organizations, and the question of what works, for whom, and in which setting, has to be central in matching client, problem, therapy, and therapist.
Speciﬁ  c models of counselling are usually differentiated by a 
number of factors:
◆Basic assumptions or philosophy
◆Formal theory of human personality and development

◆Clinical theory deﬁ  ning the goals, principles, and processes of 
change
◆Therapeutic skills and techniques(17)
One useful distinction exists between schools  of counselling and 
theoretical approaches .(18) A theoretical approach presents a single 
position regarding the theory and practice of counselling, whereas a school is a grouping of different theoretical approaches with common characteristics(see Table 6.3.1.2).
The three main schools are humanist-existential, psychodynam-

ic, and cognitive behavioural. Humanistic-existential models will be described in detail, with briefer mention of psychodynamic and cognitive behavioural models, which are covered in other chapters. The section on methods also looks at the trend towards integration and eclecticism within counselling, whereby counsellors use a variety of methods and approaches adopted from different models. Although not clearly ﬁ  tting into any one school, information-
giving and problem-solving  are counselling methods widely used in 
psychiatry, and are therefore described ﬁ  rst.
Information-giving and problem-solving
Giving information  is an important part of all medical and psychi-
atric practice, reﬂ  ecting an open and collaborative approach to

atric practice, reﬂ  ecting an open and collaborative approach to 
treatment, providing patients and their carers with the material necessary for informed decision-making. For example, for people with schizophrenia or those who misuse alcohol, the provision of information about the diagnosis, causes, and potential consequences of their condition is essential for mobilizing motivation and com-pliance with treatment. Giving information about the actions and potential side-effects of a prescribed medication enables people to 
Table 6.3.1.2  Overview of counselling schools and main approaches 
(Reproduced from Nelson-Jones, R. Theory and practice of counselling 
and therapy  (4th edn.), copyright 2006, Sage Publications.)
Psychodynamic school
Classical psychoanalysis (Sigmund Freud)
Analytical therapy (Carl Jung)
Humanistic-existential school
Person-centred therapy (Carl Rogers)

Gestalt therapy (Fritz Perls)Transactional analysis (Eric Berne)
Existential therapy (Irvin Yalom and Rollo May)
Cognitive behavioural school
Behaviour therapy (Ivan Pavlov, BF Skinner and Joseph Wolpe)
Rational emotive behaviour therapy (Albert Ellis)
Cognitive therapy (Aaron Beck)Multimodal therapy (Arnold Lazarus)6.3.1 counselling

SECTION 6  treatment methods in psychiatry 1276
play an active role in pharmacological intervention. Information-
giving is always crucial when communicating a diagnosis and fundamental to counselling for risk, as in genetic counselling, and to any intervention in which the individual is helped to make decisions.
Psycho-educative methods have a place in most models of coun-
selling and psychotherapy, but have specific importance in problem-solving and cognitive behavioural models. For example, a psychologist or counsellor may describe to the client a psychologi-cal model of a speciﬁ  c condition, such as the cognitive model of 
panic, to help the client understand their particular symptoms.
Information-giving and psycho-education involves more than

Information-giving and psycho-education involves more than 
just giving information to a passive recipient. Wherever possible the individual’s curiosity about their condition is promoted, encouraging them to ask questions and, when appropriate, to ﬁ nd their own answers. The Socratic method and guided learning 
are central to cognitive approaches. Information is not provided in a didactic fashion, but in response to the client’s questions, as client and therapist are engaged in collaborative enquiry. Whatever the information given, the practitioner checks whether the client has understood the information and its meaning. Information-giving is rarely the endpoint of an intervention, serving instead as the basis for decision-making or continuing therapeutic work.
Problem-solving  has been used and empirically validated as a 
speciﬁ  c treatment, particularly for depression, and is used by many

speciﬁ  c treatment, particularly for depression, and is used by many 
cognitive behavioural and humanistic counsellors. Problem-
solving forms a major part of brief solution-focused therapy.
(19)
From a problem-solving perspective, depression results from the 
interaction between negative life events, current problems, and deﬁ cient problem-solving abilities, and therefore facilitating solv-
ing problems is a means to alleviate depression.
(20) Therapist and 
client work collaboratively to identify and prioritize key problem areas, break them down into speciﬁ  c manageable tasks, solve prob-
lems, and develop appropriate coping behaviours. The approach involves several stages:
◆ Identiﬁ  cation and formulation of the client’s problem(s)
◆ Setting clear and achievable goals
◆ Generation of alternatives for coping
◆ Selection and operationalization of a preferred solution

◆ Evaluation of progress, with further problem-solving as 
necessary
Research in the United Kingdom has shown that problem-
solving delivered by general practitioners is as effective as pharma-cological treatment for moderate and major depression in primary care.
(21,22)  The intervention can be extremely useful for clients 
who do not want or cannot tolerate pharmacological treatment and is recommended in NICE guidelines as a treatment for mild depression. It can be offered by counsellors, general practitioners, and nurses, and may be a means to improve treatment adherence for people with psychotic disorders, as part of a psycho-education-al intervention including motivational interviewing.
(23)
Brief solution-focused therapy  developed from its roots in family

(23)
Brief solution-focused therapy  developed from its roots in family 
therapy to applications in counselling, mental health, group work, education, drug and alcohol work, social work, and business. It is the preferred mode of working for counsellors in the workplace, given its brief and focused approach. The model arose from family therapists’ observations that clients made significant changes 
when focusing on their preferred futures rather than on current problems. By articulating solutions, and building on existing skills and strengths, clients saw their problems in a different light and could effect change.
The ‘miracle question’ is a classic method of solution-focused 
therapy which is integrated into other models. The client is asked to think about and describe waking up one day to ﬁ  nd that all

therapy which is integrated into other models. The client is asked to think about and describe waking up one day to ﬁ  nd that all 
problems have vanished. The counsellor explores the impact of the miracle on people and situations. The question enables the client to get into a problem-solving cognitive set, enabling identiﬁ  cation 
of what needs to happen for the problems to change. The method has been studied in a range of client groups and settings, including with repeat offenders in the forensic service, and can produce 
positive outcomes.
(19)
Humanistic and existential models
Humanistic and existential approaches include person-centred 
therapy, gestalt therapy, transactional analysis, and existential approaches. Of these, the person-centred model is the most well known, and the one that comes most readily to mind when describ-ing the philosophy of counselling.

Client-centred ,orperson-centred  as it is more often called, 
counselling originates from the work of Carl Rogers, whose empha-sis on the recognition and empowerment of the help-seeker challenged the perceived authoritarianism of both the medical model and psychoanalysis. The model highlights respect for the person, and adopts the optimistic assumption that each person has an inner potential for healthy development and achievement, or ‘self-actualization’ . Person-centred approaches often use the analo-gy of a plant to describe the concept of growth and change. No one 
can make a plant grow, but if the plant is provided with the right conditions—water, light, soil, nutrients—then it will become the

can make a plant grow, but if the plant is provided with the right conditions—water, light, soil, nutrients—then it will become the 
best plant it can be. Person-centred therapy assumes that people have an inbuilt motivation to change, and also have the skills neces-sary with which to effect changes. Rogers’ model of counselling is non-directive. The counsellor’s task is to create the core relation-ship conditions of empathy, warmth, unconditional positive regard, and genuineness, described above, in which the client’s inner resources and potential will be unlocked, leading to the spontane-ous resolution of problems and developmental growth.
The central features of person-centred counselling form the 
bedrock of other models of counselling, including cognitive approaches. Carl Rogers, in initiating the person-centred approach, has also had a wide inﬂ  uence in the helping professions—the term

bedrock of other models of counselling, including cognitive approaches. Carl Rogers, in initiating the person-centred approach, has also had a wide inﬂ  uence in the helping professions—the term 
‘person-centred’ is used frequently in policy documents and guide-lines within health care organizations, as one of the standards of service and as a philosophy of health care.
While a non-directive and reﬂ  ective approach has value, and may 
be useful for initial data-gathering and supportive work, caution must be applied to the use of Rogerian counselling in psychiatry. Resource constraints require practitioners to impose time limits on counselling, which therefore must be more focused and ‘active’ . Furthermore, very disturbed people may be unable to access an inner potential for spontaneous change and growth, implicit within the client-centred model. There are some for whom a reﬂ ective non-directive approach may be harmful, risking an over-

whelming upsurge of avoided or forgotten memories of traumatic experiences without providing methods for coping with them.

1277
Victims of childhood sexual abuse or other destructive experiences 
may be re-traumatized by unstructured reﬂ  ective counselling.
It is likely that the person-centred approach will continue to 
form the basis of good counselling and psychotherapeutic practice regardless of the model used, with increased emphasis on more ‘skills-based’ approaches such as cognitive behavioural and other models that lend themselves more easily to measurement, structured working, and evidence-based practice.
Gestalt therapy  was originated by Fritz Perls, who described his 
approach as dealing with the total existence of a person, rather than being primarily occupied with symptoms or character structure.
(24)
Gestalt therapy argues that the past is past and the future unknow-able, therefore the focus of counselling should be the present moment—an approach, interestingly, espoused by the develop-ment of mindfulness in psychiatry and psychotherapy.
(25) The goal

(25) The goal 
of therapy is to put clients in touch with what they are thinking, feeling, and sensing, in the here and now, and how they restrict or limit themselves by continual focus on the past or future. Gestalt therapists regard the therapeutic relationship as a ‘working’ relationship, with client and counsellor taking responsibility for themselves. Attaining awareness is an essential aim within the relationship.
Gestalt therapy uses many techniques, including dream-work 
and psychodrama. The classic ‘two chair’ method of gestalt therapy enables clients to work with ‘unﬁ  nished business’ which may be 
inﬂ uencing current problems. For example, a client with memories 
of a difﬁ  cult relationship with a parent is encouraged to have a 
dialogue with the parent in the empty chair, to see both client and parent’s point of view. The client may put themselves, meta-
phorically, in the empty chair, to enable greater understanding and 
acceptance of the self.

Research has only recently played a role in the development of 
gestalt theory and practice. Most of the studies concern the effectiveness of the two-chair method, an approach which is being integrated into other models, for example Greenberg’s
(26) emotion-
focused psychotherapy, and cognitive approaches.(13)
Transactional analysis (TA)  was founded by Canadian psychia-

trist Eric Berne, and provides a theory of personality, child devel-opment, and psychopathology as well as a theory of counselling. The method assumes, as for other person-centred approaches, that people are born with a drive for growth and health—the ‘I’m OK, you’re OK’ life position. TA characterizes the personality into three groups of ‘ego states’—parent, adult, and child, each with behavioural, social, historical, and phenomenological aspects. Psychopathology arises from the repetition of unhelpful life scripts, or patterns of being, often learned early in life. Counselling enables the individual to identify and modify problematic patterns.
Very little research has been conducted into the effectiveness 
of TA as a therapy although many theoretical concepts and practical techniques have been assimilated into psychotherapy and 
counselling.

(27) The method has also led to the concept of the 
‘reﬂ ective practitioner’ , a theme embodied by the BPS Division of 
Counselling Psychology.
Existential approaches  originated in applied philosophy, and 
focus on helping people to come to terms with life in all its confus-ing complexity. Rather than curing people of pathology, the aim is to help people deal with the contradictions, dilemmas, and para-doxes of everyday existence.
(28) Anxiety and depression, rather than 
to be avoided, are to be embraced and understood in order to live life to the full. The main method is conversational, enabling clients 
to confront rather than avoid the reality of situations.
Although existential approaches may sound idealized and 
unrealistic, much of existential therapy aims to help people build conﬁ  dence and competence in tackling everyday problems. The

unrealistic, much of existential therapy aims to help people build conﬁ  dence and competence in tackling everyday problems. The 
methods and approaches have very little outcome research, because of the opposition of existential therapists to what is seen as the reductionist tendencies of research—i.e. what is effective in therapy is not open to evaluation using standard methodology. It may be that the approach offers a number of factors which can be usefully integrated into other, more evidence-based models, such as the focus on validating experience, creation of meaning to enable traumatic events to be processed, and authenticity.
Cognitive behavioural approaches

Cognitive behaviour therapy (CBT) is currently receiving excellent press internationally, and occupies a central place in the move towards evidence-based practice. NICE recommends CBT more often than other therapeutic approaches for many psychological problems. Despite its popularity and evidence-base, cognitive approaches have not been readily embraced by the counselling world.
(13) The structured and focused approach, and use of 
techniques to promote change, rested uncomfortably with counsel-lors trained in client-centred approaches, and cognitive therapy was felt to pay insufﬁ  cient attention to the therapeutic relationship 
and to the inﬂ  uence of past events on current problems. However, 
the last few years have seen a major change in the way cognitive therapy is being adopted within counselling, and a large propor-tion of counsellors integrate at least some of the approaches into their work.

The attraction of cognitive therapy to counsellors is increasing, 
with more overt focus placed on the therapeutic relationship, long-term approaches, and schema-focused work inherent in newer models, which enables counsellors to abandon their preju-dices against CBT.
(29) There is enormous scope for counsellors to 
adopt cognitive therapy in a more systematic and rigorous manner, particularly in light of the empirical evidence supporting its effectiveness and increasing demand for briefer interventions.
(13)
However, counsellors trained in different schools of counselling can be tempted to borrow specific methods from cognitive therapy, such as monitoring negative thoughts, and to use them in an eclectic way. The risk is that the effective components of the approach such as collaboration, structure, focus and homework, may be lost, thus diluting CBT’s established effectiveness.
Psychodynamic counselling
Psychodynamic counselling(30) draws from the theoretical

Psychodynamic counselling(30) draws from the theoretical 
traditions of Alderian therapy, Jung’s analytical psychology, Freudian psychoanalysis, and Kleinian psychodynamic therapy. Psychodynamic approaches pay particular attention to past experience, particularly adverse relationship experiences during early life, the continuing inﬂ  uence of which may be mediated 
by unconscious processes. These are seen to inﬂ  uence attachment 
patterns, psychosocial development, and later psychological func-tioning. Unconscious processes derived from early experiences contribute to the generation and maintenance of abnormal psy-chological states. In psychodynamic counselling and psychotherapy, these unconscious processes may be identiﬁ  ed through examining 6.3.1 counselling

SECTION 6  treatment methods in psychiatry 1278
transference and counter-transference in the therapeutic 
relationship.
The search for the personal meaning of the client’s problem or 
symptoms is central to psychodynamic counselling. The counsellor encourages clients to talk about their difﬁ  culties, but also to reﬂ  ect 
and gain insight on spontaneous associations and attitudes towards the counsellor as potential sources of information about the presenting problems. Insight alone may be sufﬁ  cient to enable 
clients to spontaneously bring about the required changes in their lives. Psychodynamic counselling may also use methods akin to problem-solving and behavioural experiments to facilitate identiﬁ  -
cation and rehearsal of new and more adaptive interpersonal strategies.
Eclectic-integrative approaches

Many practitioners assimilate conceptual and practical way of working that can be attributed to more than one theoretical perspective, formulating the client’s difﬁ  culties and choosing a 
mix of methods using more than one theoretical framework. Formally working with a variety of models and methods may be described eclectic or integrative.
(31) Such generic therapies often 
emphasize non-speciﬁ  c factors such as building the therapeutic 
alliance and engendering hope. Whether this gives the best of each world, or risks the worst of all, is very much open to question, and by nature, eclectic therapy is difﬁ  cult to standardize for RCTs. The 
worst kind of eclecticism  may be an arbitrary pick-and-mix

worst kind of eclecticism  may be an arbitrary pick-and-mix 
approach, whereby a generically skilled counsellor trains in a vari-ety of approaches and applies these with clients in a way in which he or she deems best. There is little evidence that such an approach is any more effective than the core conditions of counselling allow. Lazarus
(32) describes technical eclecticism , the drawing of inter-
ventions from different sources without necessarily subscribing to their founding discipline. Wherever possible, technically eclec-tic therapists use treatments based on empirical evidence and client need.
Integration , in contrast, combines identiﬁ  able and speciﬁ  c aspects 
of models in a predetermined way, allowing the evolution of a deﬁ ned form of therapy such as cognitive analytic therapy .
(33)
Psychodynamic interpersonal therapy  offers NHS counsellors a point

(33)
Psychodynamic interpersonal therapy  offers NHS counsellors a point 
of convergence between predominantly humanistic counselling and more clinically and dynamically orientated approaches often used within psychiatry.
(34)
Integration and eclecticism in counselling and therapy will no 
doubt continue to develop as the nature of clients’ problems and the ways of doing therapy evolve. Environmental and technological changes may lead to increasing use of the Internet in counselling and psychotherapy, with face-to-face interactions possible even when client and counsellor are in different locations. It is essential that new counselling approaches are thoroughly supported by empirical evidence so we do not see creeping eclecticism washing out the effectiveness of established methods.
Applications of counselling to speciﬁ  c 

Depending on the settings in which they work, counsellors need to 
be equipped to work with clients with a range of psychological difﬁ culties. For example, the primary care counsellor’s caseload is 
likely to include client difﬁ  culties ranging from mild to moderate anxiety or depression to bereavement and relationship problems. 
Whether or not counselling is an effective intervention for the 
range of problems seen in these settings has not yet been clearly established. The following looks at counselling for problems where there is good evidence for effectiveness.
Common psychological problems
A Cochrane systematic review(35) compared counselling with nor-
mal GP care for people suffering from anxiety, depression, or stress disorders. The authors concluded that overall, signiﬁ  cant beneﬁ  ts

mal GP care for people suffering from anxiety, depression, or stress disorders. The authors concluded that overall, signiﬁ  cant beneﬁ  ts 
were seen in mental health improvement from counselling com-pared with usual GP care, or GP care plus antidepressant treatment, in the short-term (up to 4 months). However these beneﬁ  ts were 
not maintained in the longer term, over 9 to 12 months. Counselling may be more effective for depression than as a treatment for anxiety. Barrowclough et al .
(36) compared CBT with supportive 
counselling (SC) in the treatment of anxiety symptoms in older adults. The CBT group did better than the SC group following treatment, and at follow-up. Overall, cognitively orientated models of counselling and therapy are more effective for depression and anxiety in the long-term than generic counselling. However, coun-selling may enable people to recover more quickly from depression, and is therefore a valuable and valued intervention.

Counselling for adjustment disorder
Adjustment disorder is deﬁ  ned as a problematic response to a normal
stressor, not caused by another mental health problem or bereave-ment. Such stressors include normal transitions such as leaving home, migration, adverse interpersonal experiences (e.g. relation-ship breakdown), and unexpected losses such as redundancy. Individual vulnerability can play a part in a person’s reaction to life changes, such as previous losses or other adversity, social or cultural isolation, economic deprivation or physical illness.
Counselling is recommended as the ﬁ  rst line of treatment for 
people having difﬁ  culty adjusting to life events, illnesses, disabili-
ties or losses, including childbirth and bereavement.
(4) The coun-
selling relationship is an important source of security when much has changed in the person’s life. The client is helped to identify the stressors, to explore the personal signiﬁ  cance of the changes

experienced, and to express the emotions generated. It can be nec-essary to examine unresolved past experiences which may impact on the current adjustment—for example, an individual may not begin to come to terms with redundancy until he recognizes and addresses his unresolved feelings about being abandoned by a parent in childhood. Problem-solving methods are used to identify adaptive goals and ways they may be achieved. The counsellor may encourage the client not to use unhelpful solutions such as denial, excessive use of alcohol, or emotional suppression. The aim is for the client to resolve the crisis themselves.
Relationship problems

Government statistics from both the United States and the United Kingdom show that an ever-growing proportion of marriages fail, with around one in two marriages ending in divorce and an even higher rate in other relationships. Many divorces and relationship problems involve children under the age of 16. A number of spe-cialized serv ices have evolved, including pre-marital counselling, 
counselling for sexual problems, infertility counselling, bereavement and divorce counselling, and counselling for those involved in

1279
second and subsequent relationships.(37) T elephone counselling 
and drop in services are frequently used by individuals and couples aiming to clarify the problems and ﬁ  nd appropriate help. The kind 
of issues couples bring to relationship counselling include:
◆ Communication difﬁ  culties
◆ Conﬂ  icts in need between different parties
◆ Extra-relationship affairs
◆ Sexual problems
◆ Conﬂ  icts as parents
◆ Gender role changes
◆ Violence
◆ Substance abuse
◆ Jealousy or possessiveness
Because of the wide range of difﬁ  culties, relationship counsellors 
tend to offer a variety of interventions rather than working within one therapeutic model, and it is unclear whether any one theoreti-cal approach is generally more effective than another.
(38) Brief,

(38) Brief, 
dynamic work can start the process of internal change, so that the couple is able to work on their own to practise new patterns of relating. Brief, focused work can offer immediate and early solu-tions to issues which might otherwise threaten the relationship. Longer interventions may be required for couples dealing with major life events and experiences, and offer the opportunity to look at childhood and other roots of persistent or destructive patterns of relating.
The effectiveness of counselling depends a great deal on the 
willingness of participants to engage in a process which can be painful, challenging often long-established patterns of relating, and one partner in the relationship may be more enthusiastic than the other to promote change. Research shows that many of those who experience relationship counselling understand themselves better, 
become less emotionally disturbed and understand their partner 
and relationships better.

(39) In some cases, a good outcome is for 
the relationship to end, in a way which causes least disruption to all parties including children. In the latter case, referral to other agencies may be essential, such as when child protection issues are involved.
Grief counselling
Grief is not a pathological state in itself, and most people emerge from the natural grieving process in a healthy way. Counselling has a role both in facilitating grieving for those who experience difﬁ culties in the process, and in helping those with complex grief 
reactions.
(40) Counselling might involve more than one person in a 
bereaved family or other grouping, for example the college friends of a student killed in an accident.
In health settings grief counselling is undertaken by trained

In health settings grief counselling is undertaken by trained 
professionals or volunteers, and in the community by self-help voluntary agencies such as Cruse (in the United Kingdom) or groups attached to hospices.
(41) Voluntary agencies are often staffed 
by people who have themselves experienced bereavement, and group counselling in this context provides a valuable opportunity for acceptance, sharing of experience, and the hope borne out of talking with others who have already come to terms with their loss.The research on grief counselling
(42) shows that professional ser-
vices and professionally supported voluntary and self-help services can reduce the risk of psychiatric and physical problems following bereavement, and reduce the risk level of ‘high-risk’ widows to that of a ‘low-risk’ group. Reid et al.
(43) found that support by hospice

(43) found that support by hospice 
volunteers of high-risk bereaved relatives substantially reduced their levels of anxiety and need for medical care.
Drug and alcohol problems

Drug and alcohol dependence and related problems generate many controversies about their nature and treatment, such as whether people diagnosed as alcoholics can ever return to harm-free, con-trolled drinking, and the motivation and ability of those addicted to drugs and alcohol to change. Many volunteer agencies offer drug and alcohol treatments, advocating a multifaceted approach, with a combination of methods drawn from motivational interviewing, person-centred and cognitive behavioural therapy known as ‘motivational enhancement therapy’ . There are several different models of drug and alcohol use, including that of Narcotics Anonymous, similar to Alcoholics Anonymous, who view substance abuse as a pre-existing, biochemical abnormality, necessitating life-long abstinence. Other views seek to minimize the harm caused by drugs and alcohol, by reducing risks, reducing intake, and possibly changing to another, less harmful substance. A third view sees addic-tion as a pattern of

views seek to minimize the harm caused by drugs and alcohol, by reducing risks, reducing intake, and possibly changing to another, less harmful substance. A third view sees addic-tion as a pattern of inappropriate coping: cognitive behavioural principles are used to recognize and deal with situations likely to lead to drug use.

A major trial in the United States randomized 487 patients to 
one of four, 6-month, treatments. All treatments included group drug counselling following a 12-step model, focusing on achieving abstinence. The group program was offered either alone, or in combination with individual drug counselling, CBT or individual supportive-expressive psychotherapy. Attrition rates in all groups were high, with only 28 per cent completing treatment. All inter-ventions led to a reduction in drug use, but the greatest reduction was for individual plus group counselling.
(44)
Counselling for recent and past trauma

(44)
Increased public awareness of global trauma arising from natural disasters, war, and terrorism, has led to the development of psycho-logical interventions designed to prevent the onset of post-traumatic stress disorder (PTSD) in those exposed to traumatizing events. However, after many years of early interventions in the form of active single-session ‘debrieﬁ  ng’ for individuals and groups, there is 
no evidence for their effectiveness in preventing PTSD. One of the problems in the ﬁ  eld is the tendency to ‘medicalize’ normal distress 
in traumatic situations, leading to the construction of ‘disaster 
therapists’ , perhaps with limited understanding of the culture in 
which the disaster occurred, ready to offer advice and counselling 
to survivors who may not see themselves as having a mental health 
problem.
(45)
There is also no evidence that non-directive counselling is effec-

problem.
(45)
tive in treating acute stress disorder, which itself constitutes a risk factor for PTSD.
(46) Short individualized preventive interventions 
in the style of ‘psychological ﬁ  rst aid’ may be most effective.
There is no evidence that non-directive or reﬂ  ective counselling 
is effective in the treatment of post-traumatic stress disorder. The advocates of counselling for post-traumatic stress disorder describe active-focused methods such as cognitive behaviour therapy,
(47)6.3.1 counselling

SECTION 6  treatment methods in psychiatry 1280
and using debrieﬁ  ng, to enable people to build a cognitive and 
emotional account of their experiences. Given that many clients with PTSD are, understandably, mistrustful or avoidant, the methods have to be used within the context of a sound therapeutic relationship, meeting the core counselling conditions.
Postnatal depression
Postnatal depression is often mild and remits spontaneously for many women. However, effective treatment is important because of the potential adverse effect on the child’s emotional and cogni-tive development. Home-based counselling is as effective as anti-depressant medication in the treatment of postnatal depression, and is more acceptable to mothers.
(48) Counselling can be delivered 
by health visitors trained in cognitive behavioural counselling methods.
(49) The research suggests that depressed mothers beneﬁ  t

(49) The research suggests that depressed mothers beneﬁ  t 
from an opportunity to talk about their concerns, not all of which necessarily focus on their baby, with a receptive and non-judge-mental professional person. Counselling and other psychological interventions are highly acceptable to mothers with postnatal depression, and preferred over pharmacological treatment. If coun-selling and other forms of psychotherapy enable women to recover from postnatal depression more rapidly than usual care, this alone may be a valuable service to offer in addition to routine care.
Counselling settings

Counselling takes place in a large number of settings relevant to psychiatry. These include primary care, general medical settings, student counselling services, workplace counselling services, and the voluntary sector. These settings will be described below, aiming to discuss the ways in which counselling may be best adapt-ed to the individual settings, with indications of outcome data on effectiveness.
Counselling in primary care

Primary care is one of the most conspicuous areas of growth in counselling, stimulated by greater demands for alternatives to medication for emotional problems, and by continuing debate about the most effective way of managing mental health problems in primary care. The Layard report on the need for CBT for depres-sion and NICE guidelines stress the importance and effectiveness of psychological interventions including counselling, with a par-ticular focus on CBT. It is likely that the number of counsellors who practice CBT will grow in order to meet demand.
In the United Kingdom, around half of general practices employ 
a qualiﬁ  ed counsellor and the majority meet national criteria for 
good practice.
(50) The development of UK primary care counsel-
ling is no doubt part of a wider international trend towards more accessible counselling services at the primary care level.
Counsellors in primary care are a diverse group, in the patients

Counsellors in primary care are a diverse group, in the patients 
that they see, the counselling models used, and the length of coun-selling offered. Those identiﬁ  ed as primary care counsellors include 
practice nurses, health visitors, and district nurses trained in coun-selling skills; clinical and counselling psychologists; community psychiatric nurses, and social workers, and qualiﬁ  ed counsellors 
and psychotherapists. Counselling in primary care is usually provided through one of three main service delivery models
(51):
◆ Counsellors based in GP practices and provided by a local agency 
or cooperative◆ Managed counselling services provided by the PCT or mental 
health trust, with counsellors based in GP practices or a central site
◆ Voluntary agencies (in cases where PCTs have contracts to refer 
to externally managed services in the voluntary sector)

Counsellors are valued in primary care for a number of rea-
sons,(52) providing time for patients to talk through and reﬂ  ect on 
problems, where general practitioners are unable to spend the nec-essary time on individual patients, as well as a valued alternative or addition to pharmacotherapy. Counselling in primary care also facilitates early identiﬁ  cation and intervention for mental health 
difﬁ culties.
Counsellors in primary care need to be ﬂ  exible in the way that 
they work, using different models as appropriate to each client. They also need to be ﬂ  exible about boundaries and conﬁ  dentiality,

they work, using different models as appropriate to each client. They also need to be ﬂ  exible about boundaries and conﬁ  dentiality, 
communicating with general practitioners and other health profes-sionals as appropriate. Counselling is generally six to eight 50-min sessions, with a maximum of 20 sessions, and therefore focusing on presenting difﬁ  culties rather than long-term issues. The role of the 
counsellor is varied, and may include offering individual or group counselling, offering advice or training to primary care staff on 
managing mental health problems, and general consultation.
Despite the growth and popularity of counselling in primary 
care, it is not clear how effective it is compared to other models such as CBT. Studies have shown mixed ﬁ  ndings.
(9) Trials compar-
ing counselling for anxiety and depression with usual general practitioner care, CBT, and anti-depressant medication have shown signiﬁ  cantly greater clinical effectiveness of counselling compared

ing counselling for anxiety and depression with usual general practitioner care, CBT, and anti-depressant medication have shown signiﬁ  cantly greater clinical effectiveness of counselling compared 
to usual general practitioner care in the short-term but not in the long-term.
(53–55)  For people with chronic depression, there were 
no signiﬁ  cant differences between usual care, CBT and short-term 
psychodynamic counselling,(56) although at 12 months, both 
psychological therapies were superior to usual care. Counselling in primary care can be cautiously reported as a valuable service, par-ticularly for people with mild to moderate emotional disturbance as well as bereavement and relationship difﬁ  culties. Clients improve 
in the short-term, and the service is appreciated and valued by gen-eral practitioners and patients. Primary care services are probably best offered as a range of mental health services, linking closely with community mental health services.

Counselling in general medical settings
Medical patients are understandably at higher risk of psychological difﬁ culties compared to the general population, and many hospital 
departments and clinics employ counsellors as part of the multidis-ciplinary team to meet patients’ psychosocial needs.
(57) Counselling 
beneﬁ  ts patients in many hospital settings such as gastroenterology, 
cardiology, obstetrics, and gynaecology, the families of children with medical problems and disabilities and patients with diabetes, renal failure, disﬁ  gurement, cancer, head injuries, and chronic conditions 
such as multiple sclerosis.
(58) Counsellors offer what is becoming 
increasingly limited in medicine—time. A large amount of psycho-social adjustment is needed in most serious illnesses and conditions, and counsellors in health care settings are assisting people cope with potentially life’s most challenging moments.
For some conditions, such as HIV/AIDS and genetically

For some conditions, such as HIV/AIDS and genetically 
transmitted illnesses, counselling forms an important aspect of treatment. From its outset, HIV/AIDS attracted the attention of psychological therapists, since at ﬁ  rst there was little else to offer

1281
to help people deal with a strange and potentially fatal illness. 
A range of professional and voluntary services grew to support those infected. The stages of the illness present different needs, from pre-testing counselling, dealing with the emotional, social, and physical consequences of a positive diagnosis, and managing the adjustment to living with a chronic condition. Genetic counsel-
ling is specialized branch of counselling practice with increasing 
applications within psychiatry. In the coming years, the expected identiﬁ  cation of susceptibility genes for psychiatric disorders may 
bring new opportunities and expectations from patients and families for psychiatric genetics.
(59)
Counselling is usually offered through referral to a speciﬁ  c

(59)
Counselling is usually offered through referral to a speciﬁ  c 
hospital department or ward-based counsellor. Many health care workers and hospital chaplains use counselling skills, which are generally regarded as supportive and therapeutic for patients. This does not replace the need for managed counselling services delivered by trained and professional therapists.
Counselling in educational settings

Counselling services in college and university settings cater for stu-dents with a wide range of issues. Because of their age and develop-mental stage, many students have problems adjusting to the new freedoms and demands of college life and also face the developmen-tal challenges of adolescence and young adulthood—conflicts between dependence and independence, psychosexual development, issues to do with self and body image and eating disorders. Other common difﬁ  culties include ﬁ  nancial, study, and interpersonal 
problems. Mature students may also contend with the stress of jug-gling study with children and home-life, and being minorities with-in a younger peer group. With increasing admissions of overseas students, issues such as identity and loneliness will also arise.
Student counselling services are often arranged so that practical 
(e.g. ﬁ  nancial guidance or careers counselling) and psychological

(e.g. ﬁ  nancial guidance or careers counselling) and psychological 
help are offered separately to provide discreet and conﬁ  dential a ccess. 
Most clients refer themselves, but may be referred by staff or the student’s doctor. Services need to include or work closely with psychiatrists and other mental health professionals in order to meet the needs of students with mental illness. The majority present with less severe emotional or psychological problems, but these may be highly disruptive to their studies and social integration.
Short-term counselling is usually appropriate for students, partly

Short-term counselling is usually appropriate for students, partly 
because of their urgency and the structure of the academic year, but also because their natural developmental potential enables most young people quickly to change. This process may be acceler-ated even more by the intelligence inherent in students, though emotional development can lag behind intellectual development. The task of counselling has been likened to helping the young per-son back on to the track of normal psychosexual development. More severe derailments, however, may require longer counselling, specialized psychotherapy, or psychiatric treatment.
Counselling in the voluntary sector

Counselling within the voluntary sector has vastly increased, with a growing number of support groups and voluntary organizations offering counselling, mainly on self-referral basis. The most well known in the United Kingdom include Alcoholics Anonymous, Cruse Bereavement Care, Relate for relationship difficulties, and the Samaritans, with equivalent organizations in other coun-tries. Many mental health charities offer support, befriending, and counselling at a ‘grassroots’ level; some, such as MIND in the United 
Kingdom, are organized nationally, whereas others operate at a local level. These organizations contribute a great deal to mental health provision, offering the opportunity to talk through and reﬂ ect on problems, and in offering support to individuals with 
more severe mental health problems and their families.
The interface between voluntary and statutory services is varied

The interface between voluntary and statutory services is varied 
and at times uncomfortable, with the two sharing different models of care, philosophies, and policies on issues such as conﬁ  dentiality. 
There is less research on the effectiveness of counselling provision within the voluntary sector, although one study has shown it to be at least as effective as statutory provision and is often carried out by appropriately trained staff.
(60)
Counselling in the workplace
Mental health and employment are known to be signiﬁ  cantly related:

(60)
Mental health and employment are known to be signiﬁ  cantly related: 
satisfaction at work is positively correlated with mental health and the unemployed experience higher rates of mental health problems compared to those in employment. The provision of workplace counselling has steadily expanded over the past 20 years, with more than 75 per cent of medium and large organizations in Britain and North America making counselling available to their staff. Counselling may be part of a beneﬁ  ts package, occupational health, 
human resources or a service brought in to help with speciﬁ  c prob-
lems, such as redundancy. Workplace counselling can be viewed as the application of methods of brief psychological interventions that have been shown to be effective in other settings. However, a distinctive strength of seeing a counsellor in the workplace is that the counsellor will be sensitive to the combination of personal and

work pressures that the person may present. Workplace counselling 
is a systemic, as well as individual, intervention in that the organi-zation that pays the counsellor is always present, consciously or unconsciously, inﬂ  uencing the number of sessions and conﬁ  denti-
ality boundaries.
Counselling for work-related difﬁ  culties is effective in reducing 
stress-related problems at work and sickness.
(61,62)  Those who 
receive counselling are highly satisﬁ  ed, believing it helps them 
resolve their problems. Clinically signiﬁ  cant improvement in levels 
of anxiety and depression are reported in 60–75 per cent of clients. Counselling is associated not only with reduction in sickness absence but also improvement in other organizational outcomes such as more positive work attitudes, fewer accidents, and enhanced work performance.
The main provision of counselling at work include employee 
assistance programmes (EAPs) and specialized staff counselling services.

Employee assistance programmes  were ﬁ  rst introduced in the 
United States after the Second World War, to rehabilitate oil-industry employees with alcohol problems. EAPs have become widespread 
in North America and are increasing in the United Kingdom. They 
are reported to achieve good results in terms of the percentage of employees who are rehabilitated for work, the reduction in alcohol consumption, improvement of work performance, and cost savings to the company.
(63)
EAPs provide a comprehensive conﬁ  dential counselling service 
to employees and their families, allowing employee’s problems to be identiﬁ  ed and resolved at an early stage, and are normally 
incorporated into the company’s beneﬁ  ts package as a form of 
private emotional health care. EAPs include 24-h access, telephone 6.3.1 counselling

SECTION 6  treatment methods in psychiatry 1282
counselling, and helplines as well as individual counselling offered 
at short notice. One of the advantages of counselling organized through EAPs as opposed to in-house staff counselling is improved conﬁ  dentiality: staff may be reluctant to use counselling services at 
work if they are not convinced of full conﬁ  dentiality, and if they 
fear their career prospects may be adversely affected.
Staff counselling services : many private and public sector 
organizations now have in-house counselling services.
(61) One of 
the ﬁ  rst was set-up by the Post Ofﬁ  ce in the early 1980s, in recogni-

(61) One of 
tion of the need to provide emotional and psychological support to employees. Mental health issues, mainly anxiety and depression, formed 46 per cent of the caseload, as well as relationship prob-lems, alcohol problems, bereavement, assault, physical illness or disability, and social problems. Staff counselling schemes are now promoted by many health and education authorities, the Royal College of Nursing, the British Medical Association, and MIND at Work. Problem-solving and cognitive methods of counselling appear to be the most valuable models for workplace settings.
(61)
Evaluation of the London Transport Counselling and Trauma 
Unit showed that the service made huge savings in its ﬁ  rst year of

(61)
Unit showed that the service made huge savings in its ﬁ  rst year of 
operation, in terms of reduced sickness absence and other treat-ment costs. Research from the United States indicates a return for every dollar invested in Employee Assistance Programmes of between $3 and $7.
(61,62) Other beneﬁ  ts may be less quantiﬁ  able 
but nevertheless valuable. For example, a qualitative study(64) of 
police ofﬁ  cers and support staff who had received counselling for 
work-related difﬁ  culties, showed that many described themselves 
as learning something new and useful about themselves as a result of counselling. For example, an experienced detective stated, I am 
100 per cent better at listening now to a person .
Telephone and electronically delivered counselling
The telephone  is a valuable method of counselling, as shown by

The telephone  is a valuable method of counselling, as shown by 
organizations such as The Samaritans. T elephone helplines respond to millions of calls each year, and offer a means of talking about feelings and gaining support, information, and advice. The telephone is excellent for crisis intervention and short-term work—one of the key reasons why people phone telephone helplines is because they are in crisis and want to talk anonymously and conﬁ  dentially.
The telephone and teleconferencing can also be used to conduct 
some or all of a course of individual or group counselling, or as an adjunct to pharmacological treatment. T elephone advice and structured counselling improved outcome and satisfaction for clients starting antidepressant medication,
(65) and also improved 
adherence to medication.(66)
Electronically delivered counselling : since the mid-1990s, new

Electronically delivered counselling : since the mid-1990s, new 
forms of text technology—the Internet, chatrooms, email, and mobile phone texting—are being developed to deliver counselling and psychotherapy. There is an increasing body of evidence that using text to conduct a therapeutic relationship is not only possible but also in many cases more desirable than face-to-face interaction. Electronically delivered counselling has been addressed by counsel-ling organizations in the United Kingdom, United States and internationally, with published guidelines on issues such as conﬁ  -
dentiality and data protection, contracting and informed consent, assessment of suitability of clients, boundaries, and practitioner competence.
(67) The International Society for Mental Health Online (http://www.ismho.org/) was formed in 1997 to ‘promote

(67) The International Society for Mental Health Online (http://www.ismho.org/) was formed in 1997 to ‘promote 
the understanding, use and development of online communica-tion, information, and technology for the international mental health community’ .
Working electronically has beneﬁ  ts those who cannot access 
therapy because of, for example, disability or geography. Communicating from a distance can make for a more honest and 
open relationship, clients diverging information or issues which they would ﬁ  nd difﬁ  cult to discuss face-to-face. Such disinhibition 
may be empowering—clients having a cathartic experience, so they can then disappear into cyberspace—or potentially hazardous, with traumatic issues remaining unresolved. Although the evalua-tion of such services is in its infancy, and there are many issues to be addressed, such as practitioner competence and conﬁ  dentiality,

electronic forms of mental health provision are likely to increase. They provide a means of providing help to clients who not only cannot but do not wish to meet with a helper, clients who have been traditionally excluded from mental health provision.
Counselling accreditation, training, 
and registration
The number of counsellors and psychotherapists in the United 
Kingdom and other countries is growing rapidly. Professional status and accountability are key concerns about counselling and coun-sellors, along with other providers of non-medical health care
(68)—
in the past, anyone could practise as a counsellor, with no standards of training, supervision, or attachment to a regulatory body. As a result, the vulnerable users of such practitioners are at risk. However, there is a strong move within counselling towards clear standards of training and accreditation, to be able to provide an effective and accountable service to the public.

For full accreditation , professional counsellors are required to 
follow, as a minimum, a 3-year full-time training course in the theory and practice of counselling. The standards required are covered by two main organizations in the United Kingdom, with equivalents in other countries:
◆ The British Association of Counselling and Psychotherapy, which 
offers accreditation for counsellors from a variety of disciplines, mainly humanistic and psychodynamic.
◆ The British Psychological Society, which offers accredited 
chartered status for counselling psychologists, trained to meet standards in applied psychology.
The requirements for accreditation or registration vary between

The requirements for accreditation or registration vary between 
organizations. Common requirements are a minimum of 450 taught contact hours and 450 h of supervised practice, evaluated via case studies and process reports; academic knowledge of counselling theory and research; personal counselling or psychotherapy; and, for the British Psychological Society, research skills and experience. The qualiﬁ  cation requires that practitioners follow a code of 
practice and ethics, stipulating ethical practice, the need for super-vision, appropriate conﬁ  dentiality, and other standards for profes-
sional practice.
One of the problems in accreditation is ensuring that counsellors 
have followed a known and recognized training course. Alongside the expansion of interest in counselling, the number of counselling courses rises each year, ranging from short evening classes in active

1283
listening and short courses in counselling skills for health profes-
sionals, to full-time training leading to professional accreditation or chartering. A recent review of UK training found that many psychotherapy and counselling organizations are small, and a signiﬁ  cant number of training providers are linked to no external 
quality assurance systems, 63 per cent having no professional body recognition.
(69) There are a large number of titles for both training 
courses and individual counsellors and psychotherapists, which can only cause confusion to both potential trainees and the public. The review
(69) made a number of recommendations to improve 
the quality of training courses, to lead to greater standardization.
A further change within counselling is the move towards

A further change within counselling is the move towards 
registration. Currently there is no statutory protection for using the terms ‘counsellor’ or ‘psychotherapist’ , and therefore no means for the prevention of bad practice or abuse. Without registration through a professional body, clients may have no redress for incom-petent practice. The National Service Framework for mental health, which sets clear standards for the delivery of effective services, emphasize the importance of ‘talking therapies’ but stresses the need to register counsellors, psychotherapists, and psychologists. The registering organizations are now moving towards statutory registration and legal protection for the terms counsellor, psychol-ogist, and psychotherapist; and at the time of writing, deﬁ  nitive

legislation is likely to be in place by 2008 or so. In the meantime, it is vital that the public and health professionals are aware of the need to seek help only from qualiﬁ  ed practitioners of counselling.
For psychiatrists and other mental health care professionals, it 
can be difﬁ  cult to make sense of the range of counselling models 
available, and it is therefore not surprising that potential purchas-ers and consumers are similarly confused about the nature and advisability of seeking counselling. Counselling has only recently been subject to the rigorous evaluation necessary to meet the standards of evidence-based practice. The most central aspects of counselling, the therapeutic relationship, and qualitative nature of the work, can be difﬁ  cult to evaluate using established research 
methodology.
However, counselling is an evolving profession, moving away

However, counselling is an evolving profession, moving away 
from, but not forgetting, its roots in Rogerian and psychoanalytic practice, and working hard to meet standards of effectiveness, evaluation, registration, and accountability.
Far more attention is being paid to evaluation, with the develop-
ment of research paradigms suited to counselling. Systematic evaluation will eventually make it possible to identify, on the basis of clear evidence, the indications for speciﬁ  c models of counselling 
as well as their limitations. Issues of training, standards, ethics, and accountability are being addressed, to enable counselling to become fully consolidated and integrated within mental health services.
Counselling is a vital part of psychiatry for many reasons. There 
is a signiﬁ  cant gap between the demand for psychological therapy 
and the available supply. One proposal to overcome this problem is to increase efﬁ  ciency of provision through the adoption of briefer

and the available supply. One proposal to overcome this problem is to increase efﬁ  ciency of provision through the adoption of briefer 
‘minimal interventions’ within stepped care models.
(70) Counselling 
is likely to play an increasingly important part of provision of psy-chological therapies, particularly for those with mild to moderate mental health problems and social and relationship difﬁ  culties. It makes sense for interventions to be offered at an early stage of 
difﬁ culties: while many problems do resolve on their own, people 
welcome the support and understanding that counselling can offer, and it is valuable in hastening recovery from emotional distress. Counselling may be appropriate as part of the treatment for people with serious mental illness, offered by psychiatric nurses, social workers, occupational therapists, and workers in the voluntary sector.
Although CBT is being advocated as the treatment of choice for

Although CBT is being advocated as the treatment of choice for 
many psychological problems, there is a risk that over-enthusiastic endorsement of the beneﬁ  ts of CBT at the expense of other models 
may lead to a gap in care: not everyone responds to cognitive approaches, and even when they do, the level of recovery varies. Therefore, the breadth and repertoire of counsellors can add a variety and richness to mental health care provision. It is this aspect 
of the human condition, the recognition that we must learn to ‘weep for the plague, not just cure it’, that is an essential component of meaningful therapy and meaningful relationships. When we experi-ence what seems awful and horrible in our lives, we often take solace in knowing that another person understands, or, at least, is attempt-ing to understand, our pain .
(71)
My thanks to Dr Sietske Boeles and Frank Wills for comments on 
earlier drafts of the chapter.

(71)
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Guildford, New Y ork.6.3.2 Cognitive behaviour therapy
Contents
 6.3.2.1 Cognitive behaviour therapy for anxiety disorders
 6.3.2.2 Cognitive behaviour therapy for eating disorders
Zafra Cooper, Rebecca Murphy, and Christopher G. Fairburn
 6.3.2.3 Cognitive behaviour therapy for depressive disorders
 6.3.2.4 Cognitive behaviour therapy for schizophrenia
6.3.2.1 Cognitive behaviour 
therapy for anxiety disorders

Cognitive behaviour therapy for anxiety disorders is a brief 
psychological treatment (1 to 16 sessions), based on the cognitive model of emotional disorders. Within this model, it is assumed that it is not events per se, but rather people’s expectations and interpretations of events, which are responsible for the production of negative emotions such as anxiety, anger, guilt, or sadness. In anxiety, the important interpretations, or cognitions, concern perceived physical or psychosocial danger. In everyday life, many situations are objectively dangerous. In such situations, individuals’ perceptions are often realistic appraisals of the inherent danger. However, Beck
(1) argues that in anxiety disorders, patients system-

atically overestimate the danger inherent in certain situations, bodily sensations, or mental processes. Overestimates of danger can arise from distorted estimates of the likelihood of a feared event, distorted estimates of the severity of the event, and/or dis-torted estimates of one’s coping resources and the availability of rescue factors. Once a stimulus is interpreted as a source of danger, an ‘anxiety programme’ is activated. This is a pattern of responses that is probably inherited from our evolutionary past and origi-nally served to protect us from harm in objectively dangerous primitive environments (such as attack from a predator). The pro-gramme includes changes in autonomic arousal as preparation for ﬂ ight/ﬁ  ght/fainting and increased scanning of the environment for 
possible sources of danger. In modern life, there are also situations 
in which these responses are adaptive (such as getting out of the

in which these responses are adaptive (such as getting out of the 
path of a speeding car). However, when, as in anxiety disorders, the 
danger is more imagined than real, these anxiety responses are largely inappropriate. Instead of serving a useful function, they contribute to a series of vicious circles that tend to maintain or exacerbate the anxiety disorder.
Two types of vicious circle are common in anxiety disorders. 
First, the reﬂ  exively elicited somatic and cognitive symptoms 
of anxiety become further sources of perceived danger. For exam-ple, blushing can be taken as an indication that one has made a fool of oneself, and this may lead to further embarrassment and 6.3.2.1 cognitive behaviour therapy for anxiety disorders

SECTION 6  treatment methods in psychiatry 1286
blushing; or a racing heart may be taken as evidence of an impend-
ing heart attack and this may produce further anxiety and cardiac symptoms. Second, patients often engage in behavioural and cog-nitive strategies that are intended to prevent the feared events from occurring. However, because the fears are unrealistic, the main effect of these strategies is to prevent patients from disconﬁ  rming 
their negative beliefs. For example, patients who fear that the unusual and racing thoughts experienced during panic attacks indicate that they are in danger of going mad and often try to con-trol their thoughts and (erroneously) believe that if they had not done so, they would have gone mad.
Within cognitive models of anxiety disorders, at least two different

Within cognitive models of anxiety disorders, at least two different 
levels of disturbed thinking are distinguished. First, negative automatic thoughts are those thoughts or images that are present in speciﬁ  c situations when an individual is anxious. For example, 
someone concerned about social evaluation might have the nega-tive thought, ‘They think I’m boring’ , while talking to a group of acquaintances. Second, dysfunctional assumptions are general beliefs, which individuals hold about the world and themselves which are said to make them prone to interpret speciﬁ  c situations 
in an excessively negative and dysfunctional fashion. For example, a rule involving an extreme equation of self-worth with social approval (‘Unless I am liked by everyone, I am worthless’) might make an individual particularly likely to interpret silent spells in conversation as an indication that others think one is boring.
Cognitive behaviour therapy attempts to treat anxiety disorders

Cognitive behaviour therapy attempts to treat anxiety disorders 
by (a) helping patients identify their negative danger-related 
thoughts and beliefs, and (b) modifying these cognitions and the 
behavioural and cognitive processes that normally maintain them. A wide range of procedures are used to achieve these aims, including education, discussion of evidence for and against the beliefs, imagery modiﬁ  cation, attentional manipulations, exposure 
to feared stimuli, and numerous other behavioural assignments. Within sessions there is a strong emphasis on experiential work and on working with high affect. Between sessions, patients follow extensive homework assignments. As in cognitive behaviour therapy for other disorders, the general approach is one of collaborative empiricism in which patient and therapist view the patient’s fearful thoughts as hypotheses to be critically examined and tested.
Historical development of cognitive behaviour therapy

Modern cognitive behaviour therapy for anxiety owes its develop-ment to pioneering work since the 1950s and 1960s in which the principles of classical conditioning were applied to the understand-ing and treatment of phobias.
(2) It was argued that (a) phobic stimuli

are conditioned stimuli that acquired their aversive properties by being paired on one or more occasions with a traumatic event, and (b) avoidance is the main reason why phobias fail to extinguish. This suggestion led naturally to the development of various forms of exposure therapy, in which patients were systematically exposed to phobic stimuli. Initially therapists were concerned that elicita-tion of strong anxiety responses would be counter-therapeutic so exposure was very gradual, often starting with brief, imaginal presentations, followed by relaxation. Subsequent research showed that such a gentle approach was unnecessary and relatively rapid, in vivo  exposure became the norm. By the mid-1970s, it was 
clear that up to 70 per cent of phobics obtained worthwhile improvements from in vivo  exposure.
(3) However, many were less

(3) However, many were less 
than fully recovered and it was not clear how exposure therapy could be applied to non-phobic anxiety states (such as panic disor-der and generalized anxiety disorder). In an attempt to enhance treatment effectiveness further, researchers attempted to identify additional factors that might maintain anxiety. Several cognitive processes outlined below received empirical support. As a conse-quence, more comprehensive cognitive behavioural treatments that attempt to modify a range of maintaining factors were developed. This chapter describes these treatments.
Cognitive content of anxiety disorders
Although there is no substitute for a careful assessment of each patient’s ideation, research shows that most anxiety disorders are characterized by a speciﬁ  c type of fearful ideation and successful 
therapy generally focuses on such ideation.
(4)
(a) Panic disorder

(4)
Panic disorder is characterized by a fear of an immediately impend-ing internal disaster (e.g. heart attack, cessation of breathing, mental derangement) and a sense of loss of control over physical and mental functions. Many of panic patients’ negative thoughts can be viewed as misinterpretations of normal bodily sensations (such as palpitations or a slight feeling of breathlessness). Indeed, cognitive theorists
(5) argue that panic attacks result from a vicious circle in 
which catastrophic misinterpretations of body sensations lead to an increase in anxiety and associated sensations, which are in turn 
interpreted as further evidence of impending, internal disasters (e.g. heart attack, fainting, going mad). Panic disorder with agora-phobia is often also accompanied by fear of the interpersonal consequences of attacks (e.g. ‘I’ll make a fool of myself’).
(b) Social phobia

Social phobia is characterized by exaggerated fears of being evalu-ated, of having one’s weaknesses exposed, and of being judged adversely by other people. While in feared social situations, the social phobic continually monitors his or her performance, fears that this performance will be viewed as evidence that he or she is inept, boring, or stupid, and expects that such judgements will have dire long-lasting implications (loss of status or worth and failure to achieve key goals such as friendship, marriage, promotion). Often social phobics have excessively high standards for social performance (e.g. ‘My speech must be perfectly ﬂ  uent’ , ‘I must 
always appear intelligent and witty’). Typically, social anxiety is triggered when individuals have a strong desire to convey a particular, favourable impression of them and have marked insecurity about their ability to do so.
(c) Generalized anxiety disorder

Generalized anxiety disorder is characterized by excessive worry about a number of life circumstances (e.g. ﬁ  nance, health, work, 
children, etc.) and the subjective impression that the worry is difﬁ cult to control.
(6) Beck et al.(7) suggested that generalized anxiety 
disorder patients are anxious about many topics because their beliefs about themselves and the world make them prone to inter-pret a wide range of situations and circumstances in a threatening fashion. Although their beliefs are quite varied, Beck suggested that they mainly revolve around issues of acceptance, competence, responsibility, and control, as well as the symptoms of anxiety. Borkovec et al .
(8) have shown that, compared with non-patients,

1287
the worry of general anxiety disorder patients involves less imagery 
about speciﬁ  c feared outcomes and more verbal rumination in 
which problems are cast in a more abstract, more difﬁ  cult to solve, 
form. Wells(9) has highlighted the importance of positive and nega-
tive beliefs about worry (meta-cognition).
(d) Obsessive–compulsive disorder
Obsessive–compulsive disorder is characterized by intrusive and 
distressing thoughts, impulses, or images about possible harm coming to oneself or others. Thoughts with a similar content to the intrusions of obsessional patients (e.g. a young mother having an intrusive thought about dropping her baby) are common in the 
general population.
(10) For this reason, it has been suggested that 
the key cognitive abnormality in obsessive–compulsive disorder is not the content of obsessional thoughts, but rather the way the thoughts are interpreted.
(11) In particular, it would appear that

(11) In particular, it would appear that 
obsessional patients interpret recurrent obsessional thoughts and impulses as a sign that something terrible will happen, for which they will be responsible. For example, the young mother mentioned above may think that because she had a thought of dropping her baby, she is very likely to do so, despite ﬁ  nding the idea repugnant. 
In order to prevent the feared consequences of their obsessional thoughts, patients engage in a wide range of ‘putting right’ acts including (when relevant) washing and checking.
(e) Post-traumatic stress disorder
Surveys(12) indicate that unwanted, intrusive, and distressing mem-

ories and the other symptoms of post-traumatic stress disorder (avoidance of reminders and hyperarousal/numbing) are common immediately after traumatic events. Over the next few months many people recover but in a subgroup post-traumatic stress disor-der becomes chronic. It is the latter group that normally present for treatment. Research indicates that chronic post-traumatic stress disorder is associated with appraising the traumatic event and/or its sequelae in a manner that would produce a sense of serious current threat to one’s view of oneself and/or the world.
(13)
Examples are given in Table 6.3.2.1.1. There is also evidence that chronic post-traumatic stress disorder tends to be associated with a fragmented memory for the traumatic event and that recovery is associated with developing a more coherent narrative.
(14,15)
Why do negative thoughts and beliefs persist?

(14,15)
If the world is not as dangerous as anxiety disorder patients assume, why do they not notice this and correct their thinking? For many patients with chronic anxiety disorders, the persistence of their fears can seem strangely irrational, at least at ﬁ  rst glance. Consider, 
for example, panic disorder patients who think during their panic attacks that they are having a heart attack. Before they come for treatment they may have had several thousand panic attacks, in each one of which they thought they were dying, but they are not dead. Despite what might appear to an outsider as stunning disconﬁ  rmation of their belief that a panic attack can kill, their 
thinking has not changed.
Several factors that appear to prevent patients from changing 
their negative thinking are outlined below. Such factors are impor-tant because reversing them is likely to be a particularly efﬁ  cient 
way of treating anxiety disorders.

(a) Avoidance, escape, and safety-seeking behaviours
Early conditioning theorists identiﬁ  ed avoidance of, and escape from, 
feared stimuli as important factors in the maintenance of anxiety disorders. It is easy to see how avoidance of a feared situation (e.g. a 
supermarket for an agoraphobic) or escape from the situation before a feared event (e.g. a panic attack) occurs could prevent phobics from disconﬁ  rming their fears. However, situational avoidance/escape is 
not so obviously relevant to non-phobic anxiety and some phobics regularly endure feared situations without marked improvement in their fears. Salkovskis
(16) introduced the concept of in-situation

(16) introduced the concept of in-situation 
safety behaviours to deal with this problem. In particular, Salkovskis suggested that while in feared situations most patients engage in a variety of (often subtle) behaviours that are intended to prevent, or minimize, a feared outcome. For example, cardiac concerned panic disorder patients may sit down, rest, and slow down their breathing during attacks and believe, erroneously, that performing these safety behaviours is the reason why they did not die. Experimental studies have conﬁ  rmed that (a) anxious patients engage in safety behaviours 
while in feared situations, and (b) dropping these behaviours facili-tates fear reduction.
(4)
Recent work(17) has highlighted several other important features

(4)
Recent work(17) has highlighted several other important features 
of safety behaviours. First, although termed ‘behaviours’ , many are internal mental processes. For example, patients with social phobia who are worried that what they say may not make sense and will sound stupid, often report memorizing what they have said and comparing it with what they are about to say, whilst speaking. If everything goes well, patients are likely to think ‘It only went well because I did all the memorizing and checking; if I had just been myself people would have realized how stupid I was’ . In this way their basic fear persists. Second, it is common for patients to engage in a large number of different safety behaviours while in a feared situation. Table 6.3.2.1.2 illustrates this point by summarizing the safety behaviours used by a patient who had a fear of blushing, especially while talking to men whom she thought other people would think were attractive. Third, safety behaviours can create

some of the symptoms that patients fear. For example, responding 
to a feeling of breathlessness in panic attacks by breathing more quickly and deeply (hyperventilating) can enhance the feeling of being short of breath. Similarly, post-traumatic stress disorder patients who are concerned that unwanted intrusive recollec tions of the trauma mean they are going mad and often try hard to sup-press such recollections. Unfortunately, active suppression increases the probability that the intrusion will occur. Fourth, some safety 
Table 6.3.2.1.1  Some examples of idiosyncratic negative appraisals 
leading to a sense of current threat in post-traumatic stress disorder
What is appraised? Negative appraisal
Fact that trauma happened ‘Nowhere is safe’
One’s behaviour/emotions during trauma ‘I cannot cope with stress’; ‘It 
 was my fault’
Initial post-traumatic stress disorder symptoms
Irritability, anger outbursts ‘My personality has changed 
 for the worse’

was my fault’
Flashbacks, intrusive recollections, and 
nightmares‘I’m going mad’; ‘l’ll lose 
 control of my emotions’
Other people’s reactions after trauma
Positive responses ‘They think I am too weak to 
cope on my own
Negative responses ‘Nobody is there for me’; ‘I 
 can’t rely on other people’6.3.2.1 cognitive behaviour therapy for anxiety disorders

SECTION 6  treatment methods in psychiatry 1288
behaviours can draw other people’s attention to problems that 
patients wish to hide. For example, a secretary who covered her face with her arms whenever she felt she was blushing discovered that colleagues in her ofﬁ  ce were much more likely to look at her when 
she did this than when she simply blushed. Finally, some safety behaviours inﬂ  uence other people in a way that tends to maintain 
the problem. For example, the tendency of social phobics to moni-tor continually what they have said, and how they think they come across, often makes them appear distant and preoccupied. Other people can interpret this as a sign that the phobic does not like them and, as a consequence, they respond to the phobic in a less warm and friendly fashion.
(b) Attentional deployment

Selective attention plays an important role in maintaining some anxiety disorders. Patients with panic disorder or hypochondriasis fear certain bodily sensations and symptoms, believing they indicate the presence of a serious physical disorder (heart attack, cardiac dis-ease, cancer, etc.). Such patients have often had several medical investigations that indicate they do not have the physical illness(es) they fear, but they are not convinced. One reason appears to be that their fears lead them to focus attention on relevant parts of their bodies and, as a consequence of this attentional deployment, they become aware of benign bodily sensations that other people do not notice.
(5) The presence of such sensations is then taken by the 
patient as evidence that a serious physical illness has been missed. (Hypochondriasis is classiﬁ  ed as a somatoform disorder in DSM-
IV
(6) and as a somatization disorder in ICD-10.(18) However, it has

IV
(6) and as a somatization disorder in ICD-10.(18) However, it has 
many features in common with anxiety disorders and can be con-ceptualized as such for the purposes of psychological treatment).
Social phobia appears to be associated with two attentional 
biases. First, when in feared social situations, patients with social phobia report becoming highly self-focused, constantly monitor-ing how they think and feel they are coming across, and paying less attention to other people.
(17) Reduced processing of other people means that social phobics have less chance to observe other people’s 
responses in detail and, therefore, are unlikely to collect from other people’s reactions information that would help them to see that they generally come across more positively than they think. Second, there is some evidence that when social phobics do focus on other people, they are particularly good at detecting negative reactions
(19)
and are poor at detecting positive reactions.

(19)
(c) Spontaneously occurring images
Spontaneously occurring images are common in anxiety disorders and also appear to play a role in maintenance. Patients with social phobia often report ‘observer-perspective’ images in which they see themselves as if viewed from outside.
(20)

(20)
Unfortunately, in their images they do not see what a true observer would see, but rather their fears visualized. For example, a teacher who was anxious about talking with colleagues in coffee breaks noticed that before speaking she felt tense around her lips. The tension would trigger an image in which she saw herself with a twisted and contorted mouth, looking like ‘the village idiot’ . At that moment, she was convinced everyone else thought she was stupid. Negative images are also used as information in other anxi-ety disorders. For example, obsessional patients who have images of committing a repugnant act (e.g. stabbing one’s child) take the occurrence of the image as evidence that they are in danger of performing the act. Similarly, patients with post-traumatic stress disorder report that ﬂ  ashbacks increase the perceived likelihood of 
a future trauma.
(d) Emotional reasoning

A further source of misleading information that can enhance patients’ perception of danger is anxiety itself.
(21) For example, 
social phobics often think they look as anxious as they feel, but in general this is not the case.
(22) Similarly, generalized anxiety disorder 
patients often take feeling on edge as a sign that something bad is about to happen.
(e) Memory processes
Some anxiety disorders are associated with a tendency for the selec-tive recall of information that would appear to conﬁ  rm the patient’s 
worst fears. For example, high socially anxious individuals selec-tively recall negative information about the way they think they have appeared to others in the past when anticipating a stressful social interaction.
(22) Similarly, patients with hypochondriasis

(22) Similarly, patients with hypochondriasis 
selectively recall illness-related information. In post-traumatic stress disorder, a failure to elaborate memories at the time of the trauma and enhanced associative learning appear to play a key role in maintaining the re-experiencing symptoms.
(13)
(f) Rumination
Anxious patients often spend protracted periods of time ruminatingabout negative things that could happen in the future and about how bad they would be. They may also ruminate about things that they feel have gone wrong in the past. Studies by Davey and Matchett
(23) indicate that such rumination can enhance fear. There

(23) indicate that such rumination can enhance fear. There 
are several ways in which rumination might operate. First, thinking about an event may directly increase its subjective probability. Second, selectively focusing on past negative events, feelings, and impressions may further enhance the perceived likelihood of future danger. Third, rumination is rarely focused on constructively pro-cessing perceived threats, but instead often seems to elaborate the Table 6.3.2.1.2  Safety behaviours associated with a fear of blushing
Feared outcome Safety behaviour intended to prevent 
feared outcome
‘My face (and neck) will go red’ Keep cool (open windows, drink cold 
 water, avoid coffee, wear thin clothes)
Avoid eye contact. If in a meeting, pretend 
 to be writing notesKeep topic of conversation away from 
 ‘difﬁ  cult’ issues
Tell myself the man is not really attractive.  He’s no more than a 2 (out of 10)
‘If I do blush, people will notice’ Wear clothes (scarf, high collar) that

‘difﬁ  cult’ issues
‘If I do blush, people will notice’ Wear clothes (scarf, high collar) that 
 would hide part of the blush
Wear make-up to hide the blush
Put hands over face. Hide face with 
 long hairStand in a dark part of the room
‘If people notice, they will think 
badly of me’Provide an alternative explanation for the 
 red face, e.g. ‘it’s hot in here’.
‘I’m in a terrible rush today’, ‘I’m recovering  from ﬂ  u’, etc.

1289
threats or make them more abstract and hence difﬁ  cult to deal 
with. For example, patients with post-traumatic stress disorder often ask themselves ‘Could I have done something different?’ during their traumatic event without thinking through in detail what their alternative options might have been, and how feasible they would have been at the time.
Treatment
Assessment interview
Table 6.3.2.1.3 summarizes the main topics covered in the assess-ment interview. The aims of the interview are as follows: (a) to obtain a detailed description of the patient’s fears and behaviour; (b) to identify maintaining factors; (c) to normalize the problem; (d) to develop a model of the problem that can be used to guide treatment.
The interview would start by asking the patient to provide a brief

The interview would start by asking the patient to provide a brief 
description of the main presenting problem(s). For example, intense anxiety attacks, anxious apprehension, and avoidance of places where the attacks seem particularly likely or would be embar-rassing. The interviewer then obtains a detailed description of a recent occasion when the problem occurred or was at its most marked. This would include the situation (‘Where were you?’ , ‘What were you doing?’), bodily reactions (‘What did you notice in your body?’ , ‘What sensations did you experience?’), thoughts (‘At the 
moment you were feeling particularly anxious, what went through

moment you were feeling particularly anxious, what went through 
your mind? What was the worst that you thought might happen? Did you have an image/mental picture of that? How do you think you looked?’), behaviour (‘What did you do?’), and the behaviour of others (‘How did X react?’ , ‘What did X say/do?’). Having obtained a detailed description of a recent occasion, the interviewer should check whether the occasion was typical. If not, further descriptions of other recent occasions should be elicited to provide a complete picture.Next a list of situations in which the problem is most likely to 
occur or is most severe is elicited (‘Are there any situations in which you are particularly likely to have a panic attack?’), together with information about modulators (‘Are there any things that you notice make the symptoms stronger/more likely to occur?’ , ‘Are there any things that you’ve noticed make the symptoms less likely/less severe/more controllable?’).

Possible maintaining factors should be identiﬁ  ed, including the 
◆ avoidance of situations or activities (‘What situations/activities 
do you avoid because of your fears?’)
◆ safety behaviours (‘When you are afraid that X might happen, is 
there anything you do to try to stop it happening?’)
◆ attentional deployment (‘What happens to your attention when 
you are worried about X? Do you focus more on your body? Do you become self-conscious?’)
◆ faulty beliefs (e.g. an obsessive–compulsive disorder patient, 
believing that thinking something can make it happen)
◆ attitudes and behaviour of signiﬁ  cant others (‘What does Y think 
about the problem?’; ‘What does Y do when you are particularly anxious?’)
◆ current medication
There are several ways in which excessive use of both prescribed

There are several ways in which excessive use of both prescribed 
and non-prescribed medications can maintain anxiety disorders. For example, painkillers and tranquillizers can cause derealization and sleep disturbance respectively, and drinking before social occasions prevents disconﬁ  rmation of one’s social fears.
It is also important to assess patients’ beliefs about the cause of 
their problems as some beliefs may make it difﬁ  cult for patients to 
engage in therapy. For example, patients with post-traumatic stress disorder who think the best way of dealing with a painful memory is to push it out of their mind are unlikely to engage in imaginal reliving of the event until this belief is dealt with.
Finally, a brief description of the onset and subsequent course of

Finally, a brief description of the onset and subsequent course of 
the problem should be obtained. This description should particularly focus on factors, which may have been responsible for initial onset and for ﬂ  uctuations in the course of the symptoms and is primarily 
used to make the development of the problem seem understand-able to the patient.
It is not always possible to obtain all the information needed for

It is not always possible to obtain all the information needed for 
a cognitive behavioural formulation in an assessment interview. Sometimes it is necessary to follow-up the interview with home-work assignments in which the patient collects more information to clarify the formulation. For example, a hypochondriacal patient who was concerned that palpitations meant that she had cardiac disease was asked to record what she did each hour and how many palpitations she experienced. T o her surprise, palpitations were not associated with exercise, as she expected, but rather were most common when she was sitting quietly, reading, watching television, or studying. This realization helped convince her that her problem may be disease preoccupation rather than a faulty heart.
Developing an idiosyncratic model of the 
patient’s problem
Assessment ends with the development of an idiosyncratic version

Assessment ends with the development of an idiosyncratic version 
of the cognitive model. In particular, therapists aim to show patients Table 6.3.2.1.3  Summary of topics to be covered in assessment 
interview
Brief description of presenting problem(s)
For each problem
 Detailed description of a recent occasion when problem occurred/was at 
  its most marked  Situation
  Bodily reaction
  Cognitions  B e h a v i o u r
 List of situations when the problem is most likely to occur/be most severe
 Modulators (things making it better or worse)
 Possible maintaining factors
  Avoidance of situations/activities  Safety behaviours
  Attentional deployment
  Faulty beliefs  Attitudes and behaviour of others
  Medication
 Beliefs about cause of the problem Previous treatment (types, whether successful)
 Onset and course

Attentional deployment
Personal strengths and assetsSocial and ﬁ  nancial circumstances6.3.2.1 cognitive behaviour therapy for anxiety disorders

SECTION 6  treatment methods in psychiatry 1290
how the speciﬁ  c triggers for their anxiety produce negative auto-
matic thoughts relating to feared outcomes and how these are 
maintained by safety behaviours and other maintenance processes. 
The model is usually drawn on a whiteboard, so that patient and 
therapist can look at it and discuss it together. Figure 6.3.2.1.1 
shows an example for a panic disorder patient. His panic attack 
started with a twinge in his chest muscles, and he then had the 
thought, ‘There is something wrong with my chest area, maybe 
I am having a heart attack’ . This interpretation made him start to 
feel anxious, his chest muscles tightened up more, he started to feel 
dizzy, his heart raced more, and he then thought, ‘I’m dying, 
I’m having a heart attack’ , and also, interestingly, ‘If I don’t die, 
people will notice I’m anxious and think it is odd’ . He then engaged 
in a series of safety behaviours to try to prevent himself from dying.

in a series of safety behaviours to try to prevent himself from dying. 
He thought he had read somewhere that paracetamol (aminaceto-
phen) is good for people with heart problems and so he took a 
paracetamol. This is incorrect information, but the key point is that 
he believed it. He also sat down and rested, took the strain off his 
heart, and took deep breaths, trying to slow down his heart rate. 
He believed that the main reason he had not died was that he had 
engaged in the safety behaviours. The reader will also notice that 
some of the safety behaviours (taking deep breaths and monitoring 
the heart) will also have augmented his feared symptoms.
Figure 6.3.2.1.2 shows a further example with a social phobic 
patient. The patient’s main fear was that other people would think 
she was stupid and boring. The situation used to develop the model

she was stupid and boring. The situation used to develop the model 
was a recent coffee break at work during which the patient had dif-
ﬁ culty joining a conversation with colleagues. When attempting to 
join the conversation she had the thought, ‘I’ll sound stupid and 
everyone will think I am dumb’ . In order to prevent herself from 
sounding stupid, she engaged in an extensive set of safety behav-
iours which (a) prevented her from discovering that her spontane-
ous thoughts are interesting to other people, (b) made her appear 
preoccupied and uninterested in her colleagues, and (c) made her 
excessively self-conscious. While self-conscious, she became par-
ticularly aware of anxiety symptoms (sweaty palms, stiff muscles around her mouth) that she thought other people might see, and 
indeed, had an image of herself in which she looked very strange,

indeed, had an image of herself in which she looked very strange, 
with a twisted and rigid mouth and appeared stupid.
Normally idiosyncratic models of the form illustrated in 
Figs 6.3.2.1.1 and 6.3.2.1.2 will be developed at the end of the ﬁ  rst 
interview, and certainly not later than the second session. Such 
models are used as blueprints to help therapist and patient organize 
and develop the rest of therapy.
Monitoring progress
Once treatment has started, it is important to monitor progress 
continually in order to decide whether a particular treatment 
procedure is working or whether the case needs reformulating and 
new treatment procedures need to be implemented. Usually 
patients are asked to complete a small number of self-report ques-
tionnaires before each therapy session. Typically, these include

tionnaires before each therapy session. Typically, these include 
frequency and severity ratings for the main anxiety problems 
(often using simple 0–8 Likert-type scales), a measure of negative 
thoughts, and general measures of anxiety and depression (such 
as the Beck Anxiety Inventory(24) and the Beck Depression Inven-
tory(25)). Table 6.3.2.1.4 summarizes some of the most commonly 
used weekly measures. In some instances these are supplemented 
by more individualized diaries and ratings. More global standard-
ized measures of symptom severity are also often administered 
at the beginning, middle, and end of therapy in order to provide 
normative data (see Table 6.3.2.1.4).
Fig. 6.3.2.1.1 A cognitive model of a patient’s panic attacks. (Reproduced from 
Clark, D.M., Panic disorder: from theory to therapy.

Clark, D.M., Panic disorder: from theory to therapy. 
In Frontiers of cognitive therapy (ed. P .M. Salkovskis), pp. 318–344, Copyright 1996, 
Guildford Press, New York.) Fig. 6.3.2.1.2 A cognitive model for a patient with social phobia.

1291
Treatment procedures
A wide range of procedures can be used to modify patients’ 
negative beliefs and linked maintenance processes. For clarity the procedures are described separately. However, in practice the tech-niques are closely interwoven. Within a given session, therapists will usually use a mixture of discussion and experiential techniques to help patients to challenge convincingly their negative beliefs. As with cognitive behaviour therapy for other disorders, patients are given extensive homework assignments and it is assumed that a sizeable amount of therapeutic change is the result of homework assignments.
(a) Identifying patients’ evidence for their negative beliefs

Anxiety disorder patients usually have reasons for believing that the things they fear are dangerous, however strange their fears may seem. The therapist, therefore, tries to ‘get inside the patient’s head’ and see what the evidence is. Often the evidence is an event or piece of information that the patient has misinterpreted. Identifying and correcting such misinterpretations can be helpful. For example, a panic disorder patient believed that experiencing high anxiety could kill her. When asked by the therapist what her evidence was, she explained that she had seen it happen. Further enquiry revealed she had entered Dresden the day after the ﬁ  re bombing of that city 
by the allies during the Second World War and had helped search for survivors. When opening up cellars below demolished houses, she repeatedly observed that the occupants were either dead or behaved in a dazed confused manner, even though the ﬁ  re had not

entered their cellars. She concluded that fear had killed the occupants or sent them mad. However, further questioning from 
the therapist revealed that the cellar occupants all had bright cherry-red lips. This allowed the therapist to explain that they were suffer-ing from carbon monoxide poisoning, not the effects of intense fear. This correction considerably reduced the patient’s fear of anxiety.
(b) Education
Education about the symptoms of anxiety is often helpful, espe-cially if it directly targets patients’ idiosyncratic fears and concerns. For example, post-traumatic stress disorder patients often think their ﬂ  ashbacks and emotional outbursts mean they are going mad

or have permanently changed for the worse. In such cases, detailed assessment of the patient’s post-traumatic stress disorder symp-toms and explanation that each are common reactions to a trauma can greatly help. Similarly, panic disorder patients with cardiac concerns often cite left-sided chest pain as evidence for their belief that they have a cardiac disorder. In such cases discussion of Fig. 6.3.2.1.3 (from a study of chest pain in patients referred to a cardiac clinic
(26)) is useful. In particular, the patient discovers that 
left-sided chest pain is more characteristic of non-cardiac chest pain than of either conﬁ  rmed angina or myocardial infarction.

left-sided chest pain is more characteristic of non-cardiac chest pain than of either conﬁ  rmed angina or myocardial infarction. 
Further questioning helps patients to see that the association between left-sided pain and attacks is probably a consequence of their fears. That is to say, they can experience pain on either side of the chest but only panic when it is on the left side. Finally, patients with obsessive–compulsive disorder who are perturbed by the apparently repulsive and unusual nature of their intrusive thoughts often benefit from reviewing Rachman and De Silva’s classic 
Table 6.3.2.1.4  Commonly used measures for monitoring progress
Anxiety disorder Measure
Symptoms Thoughts Global severity
Panic disorder Panic Rating Scale(63)
Panic Diary(63)
BAI(33)
BDI(2)Agoraphobic Cognitions Questionnaire(65)Fear Questionnaire(64)
Mobility Inventory(66)
Social phobia Social Summary Scales (Table 4)
BAI(33)

BAI(33)
BAI(33)
BDI(2)Social Cognitions Questionnaire(53)Liebowitz Social Anxiety Scale(67)
Social Performance Scale(68)
Social Interaction Anxiety Scale’68’
Social Phobia and Anxiety Inventory(69)
Generalized anxiety disorder BAI(33)
BDI(2)Worry Domains
Questionnaire(70)
Thought Control
Questionnaire(72)Penn State Worry Questionnaire(71)
Spielberger State Trait Inventory(73)
Obsessive- compulsive disorder BAI(33)
BDI(2)ResponsibilityInterpretations
Questionnaire
(74)Padua Inventory(75)
Yale−Brown Obsessive Compulsive 
Scale(76)
Post-traumatic stress disorder Post-traumatic Diagnosis Scale(77,78)
BAI(33)
BDI(2)Post-traumatic Cognitions Inventory(79)
Personal Beliefs and Reactions Scale(81)Impact of Events Scale(80)
Post-traumatic Diagnosis Scale(78)

BAI(33)
Owing to their length, the Post-traumatic Cognitions Inventory and the Personal Beliefs and Reactions Scale are not suitable fo r weekly administration.
BAI, Beck Anxiety Inventory; BDI. Beck Depression Inventory.6.3.2.1 cognitive behaviour therapy for anxiety disorders

SECTION 6  treatment methods in psychiatry 1292
paper(10) which demonstrated that thoughts with identical content 
to obsessional intrusions are common in the general population.
(c)  Identifying observations that contradict patients’ 
negative beliefs
As anxiety disorder patients’ beliefs about the dangerousness of 
feared stimuli are generally mistaken, patients have often experi-
enced a number of events that contradict their beliefs before they 
come into therapy. Therapists can make considerable progress, 
even in an assessment interview, by spotting these events and 
helping patients understand their signiﬁ  cance. For example, panic 
disorder patients who are worried that their symptoms mean they 
are about to have a heart attack, often report that in some attacks 
something unexpected happened to distract them (e.g. a telephone 
call) and then their symptoms went away. Therapists could then 
pause and help the patient understand what this means, perhaps

pause and help the patient understand what this means, perhaps 
asking, ‘Would a cardiologist prescribe telephone calls as a treat-
ment for a heart attack?’ The patient would probably answer ‘No’ , 
to which the therapist might reply, ‘If telephone calls would not 
stop a heart attack, how might they work? If the problem was the 
negative thought, could they help (by distracting one from the 
thoughts)?’
(d) Imagery modiﬁ  cation
Images play an important role in many anxiety disorders. Most 
images represent feared catastrophes and can be treated as predic-
tions to be tested (see behavioural experiments below). However, 
when the images are stereotyped and repetitive it is often also 
necessary to work directly with the images and to restructure them 
explicitly.
The problem with anxiety-related images is that they seem very

The problem with anxiety-related images is that they seem very 
realistic at the time they occur and, as a consequence, greatly enhance 
fear. A common restructuring technique involves discussing with the patient whether the image is realistic. Once it is intellectually 
agreed that the image is an exaggeration, patients are asked to rec-
reate intentionally the negative image and to hold it in mind until 
they start to feel anxious. They are then asked to transform 
it into a more realistic image, or an image, which convincingly 
indicates that the original image was unrealistic. A common obser-
vation is that patients’ spontaneous images generally stop at the 
worst moment. For example, agoraphobic patients who fear faint-
ing in a supermarket might see themselves collapsed on the ﬂ  oor, 
but not see themselves getting up, recovering, and going home.

but not see themselves getting up, recovering, and going home. 
A useful transformation in such cases is to ‘ﬁ  nish out’ the image 
by asking patients to run it on until they see the positive resolution. 
Of course, sometimes simply running on an image does not 
produce a positive resolution. For example, a patient who feared 
she would go mad frequently experienced an image of two men in 
white coats entering her house to take her away to a locked ward. 
In the image, the men were extremely powerful and she felt power-
less. Transformation, following suggestions from her, involved 
shrinking the men and then turning them into ridiculous looking 
(and hence non-threatening) white poodles.
An interesting observation about spontaneous imagery is that it 
often fails to incorporate positive information that would seriously

often fails to incorporate positive information that would seriously 
undermine the impact of the image, even when the patient has 
such information. For example, a mother whose children died in a 
house ﬁ  re, repeatedly experienced intrusive ﬂ  ashbacks in which she 
saw the house going up in ﬂ  ames and smelled burning ﬂ  esh, despite 
having seen her children in the mortuary, knowing that they had 
not been burnt, but instead were rapidly overcome by fumes.
For imagery restructuring to be effective it is important that it is 
not done as a cold, intellectual exercise, but instead includes elicit-
ing the affect normally associated with the image. Transformation

ing the affect normally associated with the image. Transformation 
may have to be done in several steps. It is often best to start with the Fig. 6.3.2.1.3 Distribution of chest pain in patients referred to a cardiac clinic and subsequently diagnosed as non-cardiac chest pain (NCCP) , angina pectoris (AP), or 
myocardial infarction (MI). (Reproduced from Beunderman, R. et al. (1998), Differentiation in prodromal and acute symptoms of patients with cardiac and non-cardiac 
chest pain, In Advances in theory and practice in behaviour therapy  (ed. P .M.G. Emmelkamp, et al.), Copyright 1998, Swets and Seitlinger, Taylor and Francis Group, an 
informa business.)

1293
most threatening aspect of the image. Possible alternative images 
should be generated by patients, rather than simply imposed by the 
therapist.
(e) Cognitive restructuring
All the above techniques are examples of cognitive restructuring 
in which the therapist provides information and asks a series 
of questions to help the patients challenge their fearful thoughts 
and images. A list of some of the questions that can be particularly 
useful for helping anxiety disorder patients challenge their negative 
thoughts is given in Table 6.3.2.1.5. Further useful questioning 
techniques can be found in Chapter 6.3.2.3.
It is sometimes helpful to use graphical methods for discussing 
alternatives to negative thoughts. In situations where there are sev-
eral non-threatening alternative explanations for a feared event, pie 
charts are particularly useful. When constructing a pie chart the 
therapist draws a circle which is meant to represent all the possible

therapist draws a circle which is meant to represent all the possible 
causes of a particular event and asks the patient to list all the possi-
ble non-catastrophic causes of the event and allocate a section of the 
circle to each cause. At the end of the exercise, there is often very 
little of the circle left for the patient’s negative explanations. Figure 
6.3.2.1.4 illustrates the use of a pie chart to challenge a generalized 
anxiety disorder patient’s belief that he would be 100 per cent 
responsible for people not enjoying themselves at his dinner parties. 
The belief was preventing him from making new social contacts 
after a painful divorce. Pie charts are particularly helpful for dealing 
with distorted beliefs about responsibility and hypochondriacal 
concerns (e.g. ‘Headaches mean I have a brain tumour’).
When considering the worst that could possibly happen in a

When considering the worst that could possibly happen in a 
feared situation patients frequently ignore the fact that there are 
many intermediate events, each with a probability of less than 1, 
which have to occur for the catastrophe to be realized. The inverted 
pyramid can be a good way of representing this. Figure 6.3.2.1.5 
shows an example with a patient who was afraid of blushing. His 
worst fear was that other people would think they were greatly 
superior to him if he blushed. Whenever he felt his face becoming 
hot, he was convinced other people were thinking they are superior 
to him and gloating. However, careful discussion helped him to see 
that there were many intermediate steps between him feeling hot 
and the feared outcome. Once the conditional probabilities were 
taken into account, there was only a minute chance that his worst

taken into account, there was only a minute chance that his worst 
fear would be correct.It is important to remember that anxiety results from over-
estimating the cost of feared events as well as their probability. 
Discussions aimed at modifying perceived cost are often helpful. 
This can be true even in cases where it might seem obvious that the 
feared event is objectively costly. For example, in hypochondriacal 
patients who are worried about dying, therapists may be tempted 
to focus exclusively on whether or not the patients are likely to die 
from the symptoms they are concerned about. Accepting that dying 
is a bad thing, the therapist may not be inclined to ask, ‘What would 
be so bad about dying?’ However, Wells and Hackmann(27) found 
that many hypochondriacal patients have distorted beliefs and

that many hypochondriacal patients have distorted beliefs and 
images about death and the process of dying. For example, they 
think that when they die they will remain conscious and will 
continue to experience all the pain they had up to that point. Such 
people can beneﬁ  t greatly from discussion of their beliefs about the 
cost of dying.
Table 6.3.2.1.5  Useful questions for challenging anxiety-related 
thoughts
What is the evidence for this thought?
Is there any alternative way of looking at the situation?
Is there an alternative explanation?
How would someone else think about the situation?
Are you focusing on how you felt, rather than on what actually happened?
Are you setting yourself an unrealistic or unobtainable standard?
Are you forgetting relevant facts or overfocusing on irrelevant facts?
Are you thinking in all-or-nothing terms?

Are you overestimating how responsible you are for the way things work out?
What if the worst happens? What would be so bad about that? How could 
 you cope?
How will things be x months/years afterwards?
Are you overestimating how likely the event is?
Are you underestimating what you can do to deal with the problem/situation?Fig. 6.3.2.1.4 A pie chart representing factors that might contribute to guests 
enjoying themselves at a dinner parties to challenge a generalized anxiety disorder 
patient’s belief that he would be 100 per cent responsible for people not enjoying 
themselves. (Reproduced from Clark, D.M., Anxiety states: panic and generalized 
anxiety, In Cognitive therapy for psychiatric problems: a practical guide  (ed. 
K. Hawton, et al. ), pp. 52–96. Copyright 1989 with permission from Oxford

K. Hawton, et al. ), pp. 52–96. Copyright 1989 with permission from Oxford 
University Press.)
Fig. 6.3.2.1.5 An inverted pyramid representing conditional probabilities 
between ‘feeling hot’ and ‘others thinking they are superior to you’ constructed for 
a patient who was afraid of blushing.
6.3.2.1 cognitive behaviour therapy for anxiety disorders

SECTION 6  treatment methods in psychiatry 1294
(f)  In vivo  exposure to feared situations, activities, 
and sensations
Systematic exposure to feared and avoided situations has a long 
history in cognitive behaviour therapy and is one of the most effec-tive ways of helping patients to discover that the things they are afraid of will not happen or are more manageable than they antici-pate. Initially, exposure was often conducted in imagination but it is now known that in vivo  exposure is a more effective way of deal-
ing with situational fear.
(3) During the 1970s and 1980s the domi-
nant framework for exposure was habituation. It was assumed that repeated prolonged exposure was required to achieve fear reduc-tion. More recent cognitive formulations have suggested that expo-sure is likely to be optimally effective when set-up in a way that maximizes the extent to which patients are able to disconﬁ  rm their

fears, and considerable attention is now devoted to setting up expo-sure assignments in a way that will maximize cognitive change. Before entering a feared situation, patients are asked to specify what is the worst they think could happen, how likely they think it is, and what they would normally do to prevent the feared catastrophe (safety behaviours). They are then asked to enter the feared situa-tion while dropping their safety behaviours and to observe carefully whether the feared outcome occurs. Afterwards, discus-sion focuses on whether the feared catastrophe occurred. If it did 
not, how does the patient explain its non-occurrence? Was it 
because the patient now thinks the feared outcome is unrealistic or does the patient think it was because of ‘luck’ or the continued use of safety behaviours? In the latter two instances, further exposure assignments with further encouragement to drop safety behaviours are required.
In addition to avoiding feared situations, anxiety disorder

In addition to avoiding feared situations, anxiety disorder 
patients can also avoid feared sensations. Such avoidance is partic-ularly prominent in panic disorder. For example, because of their fears about the meaning of increases in heart rate, dizziness, sweat-ing, and other autonomic cues, panic disorder patients often avoid exercise. Increasing exercise can be an excellent way of helping 
them to challenge their negative beliefs, as can other ways of inducing bodily sensations such as ingesting caffeine, and hyper-ventilating. In each instance, the key point is to help patients discover that they can experience intense physical sensations with-out dying, losing control, or experiencing some other catastrophe.
Table 6.3.2.1.6 shows a record sheet that can be useful for plan-

ning and summarizing the results of exposure assignments, with illustrations from patients with social phobia and agoraphobia. Because of the intensity of patients’ fears, and their tendency to attribute good outcomes to ‘luck’ , it is often necessary to move up a hierarchy of feared situations and to consolidate successes by repetition.
In obsessive–compulsive disorder, the compulsive rituals act 
as safety behaviours and it is necessary to ensure that patients refrain from engaging in rituals (which are often also termed

as safety behaviours and it is necessary to ensure that patients refrain from engaging in rituals (which are often also termed 
‘putting right’ acts) during exposure assignments. This procedure is called ‘exposure and response prevention’ . For example, obses-sional washers would be asked to ‘contaminate’ themselves by touching feared objects and then not put things right by washing. Similarly, obsessional checkers may be asked to expose themselves to activities that would normally provoke their checking (e.g. turn-ing on the gas cooker) and then refrain from checking more than would be normal. In both instances, patients usually ﬁ  nd 
that although exposure initially provokes considerable distress, the distress systematically declines during prolonged response prevention.
(28)
Unlike most phobic fears, the fears of obsessive–compulsive dis-

(28)
order patients (e.g. developing a fatal disease from touching an object that is believed to be contaminated) often cannot be discon-ﬁ rmed during a single or indeed multiple, exposure assignments. 
Discussing this issue, Salkovskis
(11) has suggested that exposure 
and response prevention may work by providing patients with a different understanding of their problems. In particular, the decline 
Table 6.3.2.1.6  Record sheet for noting behavioural experiments
Situation Prediction Experiment Outcome What I learned
(What exactly did you think 
would happen?
How would you know?) 
(Rate belief 0–100%)(What did you do to test the 
prediction?)(What actually happened? 
Was the prediction correct?)(1) Balanced view (rate 
belief 0–100%)?
(2) How likely is what you 
predicted to happen in future (Rate belief 0–100%)
Social phobic 
 patientCoffee break; 
  sitting with 
other teachers; trying to 
join in the

join in the 
conversationIf I just say things as they 
  come into my mind, they’ll 
think I’m stupid (50%)Say whatever comes into my 
  mind and watch them like a 
hawk; don’t focus on myself; this only gives me misleading 
information (such as images 
of myself as the ‘village idiot’), and means I can’t see themI did it and I watched the 
  others; one of them 
showed interest and we talked; she seemed to quite 
enjoy itI am probably more 
  acceptable than 
I think (70%)
Agoraphobic 
 patientShopping in a 
 supermarketI will feel dizzy and have a 
 panic attack (90%). 
 Unless I grip the trolley 
 tightly or sit down at that 
 moment, I collapse (80%)Go into the supermarket.
  When I start to feel dizzy, 
remind myself it is just anxiety, 
my heart rate is up and

Unless I grip the trolley 
my heart rate is up and 
I can’t faint. Then move away from the trolley and stand 
unsupportedI felt dizzy but didn’t faint, 
  even though I didn’t sit 
down or hold on to the 
trolleyFeeling dizzy in anxiety 
  attacks will not make me 
faint (60%)

1295
in distress during exposure and response prevention helps the 
patient to discover that they are suffering from a worry problem, rather than being in objective danger.
(g) Imaginal exposure in post-traumatic stress disorder
Although imaginal exposure is rarely used in most anxiety disor-ders, it plays an important role in the treatment of post-traumatic stress disorder. It is known
(29) that avoidance of thinking about the 
traumatic event is an important predictor of persistent post-traumatic stress disorder. In the light of this ﬁ  nding, clinicians 
have attempted to treat post-traumatic stress disorder by repeated, imaginal reliving of the traumatic event, and controlled trials
(30)

(30)
have shown that this technique is effective. At this stage it is not known why reliving works. One suggestion is that the intrusive symptoms of post-traumatic stress disorder are the result of a fragmented and disorganized memory for the trauma that is poor-ly integrated with other autobiographical information. Reliving might, therefore, facilitate the production of a more organized narrative account of the event that can be placed in the broader context of the individual’s life.
(13,31) Two types of imaginal reliving

(13,31) Two types of imaginal reliving 
have been used in controlled trials: writing out details of the event and reliving the event in imagery. In either case, it seems important to focus not only on what happened, but also on patients’ feelings and thoughts, both at the time and now, looking back at the event. Problematic idiosyncratic meanings that can be addressed with cognitive restructuring are often identiﬁ  ed during reliving 
exercises.
(h) Behavioural experiments
Behavioural experiments play a central role in the treatment of anxiety disorders. In a behavioural experiment, therapist and patient plan and implement a behavioural assignment that will provide a test of a key belief. The in vivo  exposure assignments out-
lined above are examples of behavioural experiments. Several further examples are given to illustrate the technique.
Patients with post-traumatic stress disorder often think their

Patients with post-traumatic stress disorder often think their 
intrusive recollections mean they are going mad or losing control in some way, and as a consequence, try to push the intrusions out of their mind. If this problem is identiﬁ  ed during the ﬁ  rst session 
of therapy, therapists often conduct an experiment to illustrate the undesired consequences of thought suppression. For example, the therapist might say to the patient, ‘It doesn’t matter what you think about in the next few minutes as long as you don’t think about one 
particular thing. The thing is a ﬂ  uorescent green rabbit eating my 
hair!’ Most patients ﬁ  nd they immediately get an image of the rab-
bit and have difﬁ  culty getting rid of it. Discussion then helps them

bit and have difﬁ  culty getting rid of it. Discussion then helps them 
to see that an increase in the frequency of target thoughts is a nor-mal consequence of thought suppression. This result can then be used to set-up a homework assignment in which the patient is asked to collect data to test the idea that thought suppression may be enhancing intrusions. The experiment involves not trying to push the intrusions out of one’s mind, but instead just letting them come and go, watching them as though they were a train passing through a station. Often patients report this simple experi-
ment produces a marked decline in both the frequency of intru-
sions and the belief that they are a sign of impending insanity or loss of control.
Patients with social phobia often overestimate the signiﬁ  cance of

Patients with social phobia often overestimate the signiﬁ  cance of 
their anxiety symptoms for other people. A useful behavioural experiment to illustrate this point involves having either the patient or the therapist conduct a survey in which other people are asked 
for their views about the feared symptom. For example, in the case of fear of blushing, other people might be asked:
Why do you think people blush?Do you notice other people blushing?Do you remember it?Do you think badly about people who blush?If you do, what do you think about them?’A further helpful experiment can involve intentionally display-

ing a feared symptom (e.g. handshaking or forgetting what one is talking about) and closely observing other people’s responses. A particularly effective behaviour experiment for modifying social phobics distorted self-images involves the use of video feedback. Patients are asked to engage in a difﬁ  cult social task while being 
videotaped. Afterwards they are asked to describe in detail how they think they appeared. They are then asked to view the video, watching themselves as though they are watching a stranger, ignor-ing memories of how they felt and simply focusing on how they would look to other people. In this way they often discover that they come across better than they would expect on the basis of their self-imagery. This experiment is often a powerful way of correcting distorted self-images.
Patients with panic disorder or hypochondriasis persistently 
think that normal bodily signs and/or symptoms are caused

think that normal bodily signs and/or symptoms are caused 
by a serious physical disorder. Numerous behavioural experiments can be used to demonstrate the correct, innocuous causes of their symptoms. For example, reading pairs of words which represent patient’s illness interpretations (e.g. palpitations-dying, breathlessness-suffocate) has been shown to induce feared sensations.
(5) Similarly, reproducing patients’ fear-driven behav-
iours can produce the very symptoms the patients take as evidence for a serious physical illness. For example, patients who feel short of breath in a panic attack often respond by breathing quickly and deeply (hyperventilation), which paradoxically produces more breathlessness. Similarly, patients who are concerned about cancer may palpate body parts and then take the resulting soreness or discomfort as evidence of the presence of cancer.
(i) Therapy notes

Over a series of sessions therapist and patient will generate a sub-stantial number of arguments against the patient’s fearful beliefs. In order to maximize the impact of this accumulation, patients are asked to keep a running record of evidence against their beliefs in a notebook that can easily be consulted at times of doubt. Table 6.3.2.1.7 shows an illustrative example from a panic disorder patient’s notebook. At the start of therapy, the patient had been concerned that there was something seriously wrong with his heart.
( j) Anger management
Although anxiety is the predominant problematic emotion in anxiety disorders, some patients also report signiﬁ  cant problems

Although anxiety is the predominant problematic emotion in anxiety disorders, some patients also report signiﬁ  cant problems 
with other emotions such as depression and anger. T echniques for dealing with depression can be found in Chapter 6.3.2.3. Some empirically validated techniques for dealing with anger are described here. Although presented in the context of anger accompanying anxiety disorders, these techniques are also relevant to anger in other disorders and to people without an Axis I disorder.6.3.2.1 cognitive behaviour therapy for anxiety disorders

SECTION 6  treatment methods in psychiatry 1296
(k) Cognitive content and other assessment issues
Anger is triggered when other people are seen to have broken one’s 
personal rules about what is right and fair.(1) Angry individuals 
invariably think that they have been badly treated and ascribe their perceived ill treatment to intention or unacceptable neglect on the part of others. A key ﬁ  rst step in assessment is to help patients 
become aware of their automatic thoughts during periods of anger. It is also helpful to keep a record of the situations and behaviours of other people that routinely trigger anger. Review of such triggers often reveals a particular theme and an implicit rule that the patient thinks other people should abide by. A detailed description of how the person behaves when angry and what effect the behaviour has on others is also essential.
(l) Intervention

As patients’ rules about the way that others should behave are often highly idiosyncratic, a useful tactic involves asking patients to consider whether the problem is assuming that others hold the same rule as them when they do not. This can help reduce the conviction that others’ actions are actively malicious. Other useful questions include the following.
◆ Is there any other explanation for what happened?
◆ Did the other people know that their actions would harm me?
◆ Am I mind-reading?
◆ Am I over-applying the ‘shoulds’?
◆ What are the advantages and disadvantages of responding with 
anger?
◆ Are there other ways I could behave which will be more likely to 
put things right/help me to get over it?
Although identifying and changing anger-related thoughts is a 
useful tactic, it is important to remember that anger is an action-orientated emotion. When angry, patients have a strong compul-sion to hit out verbally or physically, and have great difﬁ  culty in

useful tactic, it is important to remember that anger is an action-orientated emotion. When angry, patients have a strong compul-sion to hit out verbally or physically, and have great difﬁ  culty in 
thinking rationally. For patients with recurrent anger problems, it is often useful to teach them ﬁ  rst to pause and relax or remove 
themselves from the anger-provoking situation before trying to challenge their thoughts and to delay-taking action (such as writ-ing angry letters to others) until they have calmed down and had time to consider the appropriateness/usefulness of the action. 
T o enhance further the generalizability of thought-challenging work, it is often useful to summarize the answers to typical anger-
related thoughts on a ﬂ  ash card that patients can carry around and 
consult whenever they become angry.
Anger can sometimes be the result of  chronic under-assertiveness,

Anger can sometimes be the result of  chronic under-assertiveness, 
with patients’ fears preventing them from making their point of view known until they feel overwhelmed and irritated by the demands placed on them. In such cases, discussion of the fears that prevent earlier and more appropriate assertion and role-playing in which the patients try out and evaluate ways of communicating their views to others in a prompt and constructive fashion can be helpful.
Cognitive behaviour therapy is suitable for most patients with anx-iety disorders and the low dropout rates reported in many controlled trials
(4, 32)  suggest that it is well tolerated. In cases with

(4, 32)  suggest that it is well tolerated. In cases with 
additional severe comorbid problems (e.g. alcohol dependence, depression) it is sometimes necessary to bring these problems under control before starting cognitive behaviour therapy for anxiety. Concurrent use of prescription anxiolytic medication (benzodiazepines, tricyclics, selective serotonin reuptake inhibi-tors) is not a contraindication. At one time it was thought that anxiolytics may facilitate treatment by helping patients to confront their fears more quickly. However, there is little evidence that concurrent medication enhances initial response.
(32) In addition, 
combining medication (alprazolam or imipramine) with cognitive behaviour therapy has been shown to produce poorer long-term outcome than cognitive behaviour therapy alone in panic disorder.
(33)

(33)
The latter result suggests that if a patient is not already taking anxiolytic medication, it is probably best to start treatment with cognitive behaviour therapy alone. Medication might then be added at a later stage, if response to cognitive behaviour therapy alone is poor.
Efﬁ cacy
Controlled trials involving comparisons with other psycho logical 
iterventions and waiting-list control groups indicate that cognitive Table 6.3.2.1.7  A panic disorder patient’s notebook: evidence for the two alternative explanations for chest pains
‘There is something seriously wrong with my heart’ ‘My problem is my belief that there is something wrong with my heart’
1  I hear my heart thumping sometimes, even in my ear . But because of my 
fears I focus on my body and that makes me notice it. When I notice it

fears I focus on my body and that makes me notice it. When I notice it 
I get anxious and that makes it louder because my heart beats are bigger
2  I have chest and rib tightness throughout the day . But cardiac patients 
don’t. They get chest pain (often crushing and more localized) during 
heart attacks. It is muscle tension due to work stress. It is mild after a 
good night’s sleep and easier at weekends. It is worst after a stressful day at work
3  I occasionally get tingling in my ﬁ  ngertips.  But this is a common symptom 
of anxiety. Also deep breathing—which I do when I think there is 
something wrong—causes tingling1  I think I am dying in a panic attack and that thought makes me anxious, 
producing many more sensations and setting up a vicious circle
2  Distraction sometimes helps. That makes sense if the problem is my thoughts. It

2  Distraction sometimes helps. That makes sense if the problem is my thoughts. It 
does not make sense if the problem is a heart attack. The same argument applies to leaving the situation. That would not stop a heart attack but it makes me feel 
more comfortable and undermines the negative thoughts
3  I get symptoms most often at the end of the day, when I have come to expect 
them and have time to dwell on them
4  I have proved to myself that there is nothing wrong with my heart with vigorous 
exercise. All that happens is that my heart beats faster and pumps harder, as it 
should do in order to supply my muscles with the energy they need
Reproduced from Clark, D.M. Panic disorder: from theory to therapy. In Frontiers of cognitive therapy (ed. P .M. Salkovskis), pp . 318–44. Copyright 1996, Guilford Press. New York.

1297
behaviour therapy is an effective and speciﬁ  c treatment for panic 
disorder, social phobia, speciﬁ  c phobia, generalized anxiety dis-
order, hypochondriasis, obsessive–compulsive disorder, and post-traumatic stress disorder.
(4, 32)  Results comparing immediate 
response to cognitive behaviour therapy alone and pharmaco-
therapy alone have been mixed, with superiority for cognitive behaviour therapy, equivalence for cognitive behaviour therapy, and superiority for pharmacotherapy all being reported. In con-trast to the immediate response data, the follow-up analyses after medication discontinuation that are currently available favour cognitive behaviour therapy.
(34) However, the database is modest 
and further research is required. For anger problems, controlled trials have shown that the cognitive behavioural procedures described here are effective.
(35)
Training and supervision

(35)
Most controlled trials have used therapists who have received specialized training in cognitive behaviour therapy and there is some evidence that deviation from therapy protocols and/or poor implementation is associated with less good outcome.
(36) For these 
reasons, clinicians are likely to beneﬁ  t from specialized training

and supervision. Where local training institutes exist, it is wise to take advantage of their expertise. Even when no local institute is available, expert cognitive behaviour therapists from established centres often travel internationally to deliver workshops and supervision. Several professional organizations run regular train-ing workshops and can be contacted through the Internet. The organizations include the British Association of Behavioural and Cognitive Psychotherapies (http://www.babcp.org.uk), the Association of Behaviour and Cognitive Therapies (www.abct.org), the International Association of Cognitive Psychotherapy (http://www.cognitivetherapyassociation.org), the American Psychological Association (http://www.apa.org), and the American Psychiatric Association (www.psych.org). A comprehensive list of the compe-tencies required for the main cognitive behaviour therapies for anxiety disorders can be found at:

and the American Psychiatric Association (www.psych.org). A comprehensive list of the compe-tencies required for the main cognitive behaviour therapies for anxiety disorders can be found at: http://www.ucl.ac.uk/clinical-health-psychology/CORE/CBT_Framework.htm

A number of texts describe the theory and practice of cognitive behaviour therapy for speciﬁ  c anxiety disorders
(37–39) and for anger 
problems(40) in considerable detail. T exts are frequently updated. 
Readers interested in the latest therapy guides are recommended to visit the following websites: www.oup.com, www.oup.com/us/ttw, www.guilford.com, www.wiley.com. Video illustrations of therapy sessions are also available for some anxiety disorders (see ABCT, American Psychological Association, and Guilford Press websites).
1. Beck, A.T. (1976). Cognitive therapy and the emotional disorders .
2. Rachman, S. (1996). The evolution of cognitive behaviour therapy. 
In Science and practice of cognitive behaviour therapy  (eds. 
D.M. Clark and C.G. Fairburn), pp. 3–26. Oxford University Press, 
Oxford.
3. Marks, I.M. (1975). Behavioural treatment of phobic and obsessive-

Oxford.
compulsive disorders. In Progress in behavior modiﬁ  cation(eds. M. Hersen, R.M. Fisher, and P .M. Miller), 1, pp. 66–158. Academic 
 4. Clark, D.M. (2004). Developing new treatments: on the interplay 
between theories, experimental science and clinical innovation. Behaviour Research and Therapy ,42, 1089.
 5. Clark, D.M. (1996). Panic disorder: from theory to therapy. In 
Frontiers of cognitive therapy  (ed. P .M. Salkovskis), pp. 318–44. 
Guilford, New York.
 6. APA. (1994). Diagnostic and statistical manual of mental disorders
(4th edn). American Psychiatric Association, Washington, D.C.
 7. Beck, A.T., Emery, G., and Greenberg, R.L. (1985). Anxiety disorders 
and phobias: a cognitive perspective . Basic Books, New Y ork.
 8. Borkovec, T.D., Ray, W.J., and Stober, J.W. (1998). A cognitive

 8. Borkovec, T.D., Ray, W.J., and Stober, J.W. (1998). A cognitive 
phenomenon intimately linked to affective, physiological, and interpersonal behavioral processes. Cognitive Therapy and Research ,
22, 561–76.
 9. Wells, A. (2000). Emotional disorders and metacognition: innovative 
cognitive therapy . Wiley, Chichester.
10. Rachman, S.J. and De Silva, P . (1978). Abnormal and normal 
obsessions. Behaviour Research and Therapy ,16, 233–48.
11. Salkovskis, P .M. (1985). Obsessional–compulsive problems: a 
cognitive-behavioural analysis. Behaviour Research and Therapy ,
23, 571–83.
12. Kessler, R.C., Sonnega, A., Bromet, E., et al.  (1995). Posttraumatic 
13. Ehlers, A. and Clark, D.M. (2000). A cognitive model of posttraumatic 

14. Brewin, C.R. and Holmes, E.A. (2003). Psychological theories of 
posttraumatic stress disorder. Clinical Psychology Review ,23, 339–76.
15. Foa, E.B., Molnar, C., and Cashman, L. (1995). Change in rape 
narratives during exposure therapy for posttraumatic stress disorder. Journal of Traumatic Stress ,8, 675–90.
16. Salkovskis, P .M. (1996). The cognitive approach to anxiety: threat 
beliefs, safety-seeking behaviour, and the special case of health anxiety 
and obsessions. In Frontiers of cognitive therapy  (ed. P .M. Salkovskis), 
pp. 48–74. Guilford Press, New Y ork.
17. Clark, D.M. and Wells, A. (1995). A cognitive model of social phobia. 
In Social phobia: diagnosis, assessment and treatment  (eds. R. Heimberg, 
M. Liebowitz, D.A. Hope, and F.R. Schneier), pp. 69–93. Guilford Press, New Y ork.

18. WHO. (1992). International statistical classiﬁ  cation of diseases and 
related health problems  (10th edn). WHO, Geneva
19. Veljaca, K.A. and Rapee, R.M. (1998). Detection of negative and 
positive audience behaviours by socially anxious subjects. Behaviour 
Research and Therapy
,36, 311–21.
20. Hackmann, A., Surawy, C., and Clark, D.M. (1998). Seeing yourself 
through others’ eyes: a study of spontaneously occurring images in social phobia. Behavioural and Cognitive Psychotherapy ,26, 3–12.
21. Arntz, A., Rauner, M., and Van den Hout, M. (1995). If I feel anxious, 
there must be danger: ex-consequential reasoning in inferring danger in anxiety disorders. Behaviour Research and Therapy ,33, 917–25.
22. Mansell, W. and Clark, D.M. (1999). How do I appear to others? Social

22. Mansell, W. and Clark, D.M. (1999). How do I appear to others? Social 
anxiety and processing of the observable self. Behaviour Research and 
Therapy ,37, 419–34.
23. Davey, G.C.L. and Matchett, G. (1994). Unconditioned stimulus 
rehearsal and the retention and enhancement of differential ‘fear’ conditioning: effects of trait and state anxiety. Journal of Abnormal 
Psychology ,103, 708–18.
24. Beck, A.T. and Steer, R.A. (1993). Beck anxiety inventory manual .
25. Beck, A.T. and Steer, R.A. (1993). Beck depression inventory .
The Psychological Corporation, San Antonio, TX.
26. Beunderman, R., Van Dis, H., Koster, R.W., et al.  (1988). Differentiation 
in prodromal and acute symptoms of patients with cardiac and 6.3.2.1 cognitive behaviour therapy for anxiety disorders

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non-cardiac chest pain.  In Advances in theory and practice in behaviour 
therapy   (eds. P .M.G. Emmelkamp, W.T.A.M. Everaerd, F. Kraaimaat, 
and M.J.M. van Son). Swets & Zeitlinger, Amsterdam.
27. Wells, A. and Hackmann, A. (1993). Imagery and core beliefs in health 
anxiety: content and origins. Behavioural and Cognitive Psychotherapy ,
21, 265–73.
28. Rachman, S.J., De Silva, P ., and Roger, G. (1976). The spontaneous 
decay of compulsive urges. Behaviour Research and Therapy ,
14, 445–53.
29. Ehlers, A., Mayou, R.A., and Bryant, B. (1998). Psychological predictors 
of chronic posttraumatic stress disorder after motor vehicle accidents. 
Journal of Abnormal Psychology ,107, 508–19.
30. NICE. (2005). Post-traumatic stress disorder (PTSD): the management 
of PTSD in adults and children in primary and secondary care (Clinical Guideline 26) . National Institute for Clinical Excellence, London, 
UK (www.nice.og).

31. Foa, E.B. and Riggs, D.S. (1993). Post-traumatic stress disorder in rape 
victims. In Annual review of psychiatry  (eds. J.M. Oldham, 
32. Nathan, P .E. and Gorman, J.S. (eds.) (2002). A guide to treatments that 
work . Oxford University Press, New Y ork.
33. Barlow, D.H., Gorman, J.M., Shear, M.K., et al.  (2000). Cognitive-
behavioral therapy, imipramine, or their combination for panic disorder. A randomized controlled trial. Journal of the American 
Medical Association ,283, 2529–36.
34. Clark, D.M. and Wells, A. (1997). Cognitive therapy for anxiety 
disorders. In Review of psychiatry  (eds. L.J. Dickstein, M.B. Riba, and 
J.M. Oldham), pp. 9–44. American Psychiatric Press, Washington, DC.

35. Del Vecchio, L. and O’Leary, K.D. (2004). Effectiveness of anger 
treatments for speciﬁ  c anger problems: a meta-analytic review. Clinical
Psychology Review ,24, 15–34.
36. Schulte, D., Kunzel, R., Pepping, G., et al.  (1992). Tailor-made versus 
standardized therapy of phobic patients. Advances in Behaviour 
Research and Therapy ,14, 67–92.
37. Hawton, K.E., Salkovskis, P .M., Kirk, J., et al.  (1989). Cognitive 
behaviour therapy for psychiatric problems . Oxford University Press, 
Oxford.
38. Wells, A. (1997). Cognitive therapy of anxiety disorders: a practice 
manual and conceptual guide . Wiley, Chichester, UK.
39. Barlow, D.H. (ed.). (2007). Clinical handbook of psychological disorders
(4th edn). Guilford Press, New Y ork.
40. Howells, K. (1998). Cognitive behavioural interventions for anger,

40. Howells, K. (1998). Cognitive behavioural interventions for anger, 
aggression and violence. In Treating complex cases  (eds. N. Tarrier, 
A. Wells, and G. Haddock), pp. 295–318. Wiley, Chichester.
41. Spielberger, C.D., Gorsuch, R.L., and Lushene, R.E. (1970). Manual for 
the state—Trait anxiety inventory . Consulting Psychologists Press, 
Palo Alton, CA.
42. Clark, D.M., Salkovskis, P .M., Hackmann, A., et al.  (1994). 
A comparison of cognitive therapy, applied relaxation and imipramine in the treatment of panic disorder. British Journal 
of Psychiatry ,164, 759–69.
43. Marks, I. and Mathews, A.M. (1979). Brief standard self-rating for 
phobic patients. Behaviour Research and Therapy ,17, 263–7.
44. Chambless, D.L., Caputo, G.C., Bright, P ., et al.  (1984). Assessment for

44. Chambless, D.L., Caputo, G.C., Bright, P ., et al.  (1984). Assessment for 
fear of fear in agoraphobics: the Body Sensations Questionnaire and the Agoraphobia Cognitions Questionnaire. Journal of Consulting and 
Clinical Psychology ,52, 1090–7.
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23, 35–44.
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social anxiety scale: a comparison of the psychometric properties of self-report and clinical-administered formats. Psychological Medicine ,
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measures of social phobia scrutiny fear and social interaction anxiety. 
Behaviour Research and Therapy ,36, 455–70.
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derived inventory to measure social fears and anxiety: the social phobia and anxiety inventory. Psychological Assessment ,1, 35–40.
49. Tallis, F., Davey, G.C.L., and Bond, A. (1994). The Worry Domains 
Questionnaire. In Worrying: perspectives on theory, assessment and 
treatment  (eds. G. Davey and F. Tallis). Wiley, Chichester.
50. Molina, S. and Borkovec, T.D. (1994). The Penn State Worry 
questionnaire: psychometric properties and associated characteristics. In Worrying: perspectives on theory, assessment and treatment
(eds. G. Davey and F. Tallis). Wiley, Chichester.
51. Wells, A. and Davies, M. (1994). The Thought Control Questionnaire: 
a measure of individual differences in the control of unwanted thoughts. Behaviour Research and Therapy ,32, 871–8.

52. Salkovskis, P .M., Wroe, A.L., Gledhill, A., et al. (1999). Responsibility 
attitudes and interpretations are characteristic of obsessive compulsive disorder. Behaviour Research and Therapy ,38, 347–72.
53. Van Oppen, P ., Hoekstra, R.J., and Emmelkamp, P .M.G. (1995). 
The structure of obsessive-compulsive symptoms. Behaviour Research 
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Y ale-Brown Obsessive-Compulsive Scale (YBOCS) Part 1: development, use and reliability. Archives of General Psychiatry ,
46, 1006–11.
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a brief instrument for assessing post-traumatic stress disorder. Journal 
of Traumatic Stress ,6, 459–73.

56. Foa, E., Ehlers, A., Clark, D.M., et al.  (1999). The post-traumatic 
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Event Scale: a measure of subjective stress. Psychosomatic Medicine ,
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and exposure plus applied relaxation in social phobia: a randomised controlled trial. Journal of Consulting and Clinical Psychology ,
74, 568–78.

6.3.2.2 Cognitive behaviour 
therapy for eating disorders
Zafra Cooper, Rebecca Murphy, 
and Christopher G. Fairburn
The eating disorders provide one of the strongest indications 
for cognitive behaviour therapy. This bold claim arises from the demonstrated effectiveness of cognitive behaviour therapy in the treatment of bulimia nervosa and the widespread acceptance that cognitive behaviour therapy is the treatment of choice.
(1)
Cognitive behaviour therapy is also widely used to treat anorexia nervosa although this application has not been adequately evalu-ated. Recently its use has been extended to ‘eating disorder not

1299
otherwise speciﬁ  ed’ (eating disorder NOS),(2) a diagnosis that 
applies to over 50 per cent of cases,(3) and emerging evidence sug-
gests that it is just as effective with these cases as it is with cases of bulimia nervosa.
In this chapter the cognitive behavioural approach to the under-
standing and treatment of eating disorders will be described. The 
data on the efﬁ  cacy and effectiveness of the treatment are considered 
in the chapters on anorexia nervosa and bulimia nervosa (see Chapters 4.10.1 and 4.10.2 respectively), as is their general management.
The cognitive behavioural account of the 
maintenance of eating disorders
Although both the DSM and ICD schemes for classifying eating 
disorders encourage the view that anorexia nervosa and bulimia nervosa are distinct clinical states, consideration of their clinical features and course over time does not support this.
(4) Patients

(4) Patients 
with anorexia nervosa, bulimia nervosa, and eating disorder NOS have many features in common, most of which are not seen in other psychiatric disorders, and studies of their course indicate that most patients migrate between these diagnoses over time. This temporal movement, together with the fact that the disorders share the same distinctive psychopathology, has led to the suggestion that common ‘transdiagnostic’ mechanisms are involved in the persis-tence of eating disorder psychopathology.
(5)
Anorexia nervosa, bulimia nervosa, and most cases of eating

(5)
Anorexia nervosa, bulimia nervosa, and most cases of eating 
disorder NOS are united by a distinctive core psychopathology: patients over-evaluate the importance of their shape and weight and their ability to control them. According to the cognitive behavioural view it is this dysfunctional scheme of self-evaluation that is of cen-tral importance in maintaining these disorders. Whereas most peo-ple evaluate themselves on the basis of their perceived performance in a variety of domains of life, people with eating disorders judge themselves primarily in terms of their shape and weight and their ability to control them. Most of their other clinical features can be understood as stemming directly from this ‘core psychopathology’ , including the extreme weight-control behaviour (i.e. the dieting, self-induced vomiting, laxative misuse,  and over-exercising), the vari-
ous forms of body checking and avoidance, and the preoc cupation

ous forms of body checking and avoidance, and the preoc cupation 
with thoughts about eating, shape, and weight. Fig. 6. 3.2.2.1 provides 
a ‘transdiagnostic’ representation (or ‘formulation’) of the main processes involved in the maintenance of eating disorders.
The only feature that is not obviously a direct expression of the 
core psychopathology is binge eating, present in all cases of bulimia nervosa, many cases of eating disorder NOS and some cases of anorexia nervosa. The cognitive behavioural theory proposes that binge eating is largely a product of attempts to adhere to multiple extreme, and highly speciﬁ  c, dietary rules. These patients’ tendency

to react in a negative and extreme fashion to the (almost inevitable) breaking of these rules results in even minor dietary slips being inter-preted as evidence of poor self-control. Patients respond to this per-ceived lack of self-control by temporarily abandoning their efforts to restrict their eating. This produces a highly distinctive pattern of eat-ing in which attempts to restrict eating are repeatedly interrupted by episodes of binge eating. The binge eating maintains the core psy-chopathology by intensifying patients’ concerns about their ability to control their eating, shape, and weight. It also encourages further dietary restraint, thereby increasing the risk of further binge eating.Three further processes also maintain binge eating. First, difﬁ  -

culties in the patient’s life and associated mood changes increase the likelihood that they will break their dietary rules. Second, binge eating temporarily ameliorates such mood states and distracts patients from thinking about their difﬁ  culties. Third, if the binge 
eating is followed by compensatory vomiting or laxative misuse, it 
is also maintained because patients’ mistaken belief in the effective-ness of such ‘purging’ undermines a major deterrent to their binge eating. They do not realize that purging has little effect on energy absorption.
(6)
Patients with anorexia nervosa share the distinctive core psycho-

(6)
pathology of those with bulimia nervosa and eating disorder NOS. The major difference between patients with anorexia nervosa and those with other eating disorders lies in the fact that in anorexia nervosa under-eating predominates and therefore patients become extremely underweight. This has certain physiological and psycho-logical consequences (see Chapter 4.10.1) that contribute to the persistence of the eating disorder.
(7) For example, delayed gastric 
emptying results in a sense of fullness even after eating modest amounts of food and secondary social withdrawal magnifies patients’ isolation from the inﬂ  uence of others.
The composite ‘transdiagnostic’ formulation shown in 
Fig. 6.3.2.2.1 represents the core processes that maintain any eating disorder. The speciﬁ  c maintaining processes operating in any

Fig. 6.3.2.2.1 represents the core processes that maintain any eating disorder. The speciﬁ  c maintaining processes operating in any 
patient depend upon the nature of the eating disorder psychopa-thology present. In some cases only certain of the processes are active (for example, in most cases of binge-eating disorder), but in others (for example, cases of the binge eating/purging subtype of anorexia nervosa) most are operating. The formulation highlights the maintaining processes that need to be addressed in treatment, thereby allowing the clinician to design a bespoke treatment to ﬁ  t 
the individual patient’s psychopathology.
Evidence for the cognitive behavioural account
There is a sizeable body of research that supports the cognitive view of the maintenance of eating disorders.
(8) This includes descriptive

(8) This includes descriptive 
and experimental studies of the clinical characteristics of these Fig. 6.3.2.2.1 The transdiagnostic ‘template’ formulation of the maintenance of 
eating disorders. (Reproduced from Fairburn, C.G., Cognitive behavior therapy and 
eating disorders , Copyright 2008, Guilford Press, NY).Strict dieting; non-
compensatory weight-control
behaviour
Binge eating
Compensatory
vomiting/laxative
misuseFeatures of
under-eating and
a low weightEvents and
associated mood
changeOver-evaluation of shape and
weight and their control 6.3.2.2 cognitive behaviour therapy for eating disorders

SECTION 6  treatment methods in psychiatry 1300
patients and the research on dietary restraint and ‘counter-regulation’ 
(a possible analogue for binge eating).(9) There is also strong 
indirect support from a large body of research indicating that cognitive behaviour therapy based on this model has a major and lasting impact on bulimia nervosa (see Chapter 4.10.2) and emerg-ing evidence that this is also true of eating disorder NOS. Further support comes from the ﬁ  nding that ‘dismantling’ the cognitive 
behavioural treatment for bulimia nervosa by removing those pro-cedures designed to produce cognitive change attenuates its effects and results in patients being markedly prone to relapse.
(10) Direct 
support comes from studies that have shown that dietary restraint appears to mediate this treatment’s effect on binge eating
(11) and 
that continuing over-evaluation of weight and shape in those who have recovered in behavioural terms is predictive of subsequent relapse.
(12,13)

(11) and 
(12,13)
Transdiagnostic cognitive behavioural treatment of 
There follows a brief description of cognitive behaviour therapy for 
eating disorders. Full details are provided elsewhere.(14) The treat-
ment is outpatient-based and, as applied in research settings, involves 20 individual treatment sessions over 20 weeks for the 80 per cent or more of patients who are not signiﬁ  cantly under-
weight (body mass index over 17.5). The remaining patients with a body mass index of 17.5 or below receive 40 sessions over 40 weeks. The indications for the treatment are the presence of an eating disorder of clinical severity. It is not appropriate for those whose psychiatric state, general physical health, or degree of weight loss is such that they cannot safely be treated on an outpatient basis.
The treatment has four stages.

(a) Stage one
The aims of the ﬁ  rst stage are as follows: to educate patients about 
treatment and the disorder; to engage the patient in treatment and change, and to introduce and establish a pattern of regular eating and weekly weighing. This stage comprises approximately eight sessions which are held twice weekly over 4 weeks.
(i) Jointly creating the formulation
This is usually done in the ﬁ  rst treatment session. The therapist 
draws out the relevant sections of Fig. 6.3.2.2.1 incorporating the patient’s own experiences and terms. This helps patients to realize both that their behaviour is comprehensible and that it is main-tained by a variety of self-perpetuating mechanisms which are open to change. The formulation provides a guide to what needs to be targeted in treatment if patients are to achieve a full and lasting recovery.
(ii) Establishing real-time self-monitoring

This is the ongoing ‘in-the-moment’ recording of eating and other relevant behaviour, thoughts, feelings, and events (see Chapter 4.10.2 for an example monitoring record). Self-monitoring is initi-ated in the ﬁ  rst session and continues throughout treatment. It 
serves two purposes: it assists in the identiﬁ  cation of the patient’s 
problems and progress and, more importantly, it facilitates change by helping patients address problems as they occur.
(iii) Establishing ‘weekly weighing’
The patient and therapist check the patient’s weight once a week and plot it on an individualized weight graph. Patients are strongly encouraged not to weigh themselves at other times. Weekly in-session 
weighing has several purposes: ﬁ  rst, it provides patients with 
accurate data about their weight at a time when their eating habits are changing; second, it provides an opportunity for the therapist

accurate data about their weight at a time when their eating habits are changing; second, it provides an opportunity for the therapist 
to help patients interpret the numbers on the scale, which other-
wise they are prone to misinterpret and, third, it addresses the important maintaining processes of excessive body weight check-ing or its avoidance.
(iv) Providing education
From the second session onwards, an important element of treatment is education about weight and eating since many patients have misconceptions that maintain their eating disorder. The follow-ing topics need to be covered:
◆ Body weight and its regulation: the body mass index and its 
interpretation; natural weight ﬂ  uctuations; and the effects of 
treatment on weight.
◆ Physical complications of binge eating, self-induced vomiting, 
the misuse of laxatives and diuretics, and the effect of the eating disorder on hunger and fullness.
◆ Ineffectiveness of vomiting, laxatives, and diuretics as a means of

◆ Ineffectiveness of vomiting, laxatives, and diuretics as a means of 
weight control.
◆ Adverse effects of dieting: the types of dieting that promote binge 
eating; dietary rules versus dietary guidelines.
T o provide reliable information on these topics, patients 
are asked to read relevant sections from one of the authoritative books on eating disorders
(6,15,16)  and their reading is discussed in 
subsequent treatment sessions.
(v) Establishing ‘regular eating’

The establishment of a pattern of regular eating is fundamental to successful treatment whatever the form of the eating disorder. It addresses an important type of dieting (‘delayed eating’); it dis-places episodes of binge eating and, for underweight patients, it introduces regular meals and snacks that can be subsequently increased in size. Early in treatment (usually by the third session) patients are asked to eat three planned meals each day, plus two (or if underweight three) planned snacks and they are asked not to eat between them. Patients may choose what they eat at these times with the only conditions being that the meals and snacks are not followed by any compensatory behaviour and that there should rarely be more than a 4-hour interval between these occasions of eating. The new eating pattern should take precedence over other activities but should not be so inﬂ  exible as to preclude the

possibility of adjusting timings to suit the patients’ commitments 
each day.
Patients should be helped to adhere to their regular eating plan 
and to resist eating between the planned meals and snacks. Two rather different strategies may be used to achieve this: the ﬁ  rst 
involves helping patients to identify activities that are incompatible with eating or make it less likely, and the second is to help patients to recognize that the urge to eat is a temporary phenomenon. Through using these strategies patients learn to distance themselves from the urge to eat which they ﬁ  nd gradually fades with time.
(vi) Involving signiﬁ  cant others
The treatment is primarily an individual treatment for adults 
and hence it does not actively involve others. Despite this, it is our

1301
practice to see ‘signiﬁ  cant others’ with the patient if this is likely 
to facilitate treatment and the patient is willing for this to happen. There are two speciﬁ  c indications for involving others: if others 
could help the patient in making changes or if others are making it difﬁ cult for the patient to change by, for example, commenting 
adversely on eating or appearance.
(b) Stage two
Stage two is a transitional stage which generally comprises two appointments, a week apart. Whilst continuing with the proce-dures introduced in stage one the therapist and patient conduct a joint review of progress to date, identify problems still to be addressed, revise the formulation if necessary, and design stage three.
(c) Stage three

The aim of this stage is to address the key mechanisms that are maintaining the patient’s eating disorder. The order in which these mechanisms are addressed depends upon their relative importance in maintaining the particular patient’s psychopathology. There are generally 8-weekly appointments.
(i) Addressing the over-evaluation of shape and weight
The ﬁ  rst step involves explaining the concept of self-evaluation and 
helping patients identify the life domains which contribute to their judgement of themselves. The relative importance of these domains can be visually represented on a pie chart, which for most patients is dominated by a large slice representing shape and weight and 
controlling eating.
The patient and therapist then identify the problems inherent 
in this scheme for self-evaluation. Brieﬂ  y there are three related 
problems: ﬁ  rst, the over-evaluation of shape and weight tends to

problems: ﬁ  rst, the over-evaluation of shape and weight tends to 
marginalize other domains and thus self-evaluation is overly dependent on performance in one area of life; second, the area of controlling shape and weight is one in which success is elusive, thus undermining self-esteem; and third, the over-evaluation leads to behaviour which is unhelpful and which itself maintains the disorder.
The ﬁ  nal step in educating about self-evaluation involves identi-
fying its three main expressions which occur to varying degrees in different patients. These are body checking, body avoidance, and feeling fat. The therapist explains how these behaviours and experi-ences serve to maintain and magnify the patient’s concerns about shape and weight and it is agreed therefore that they need to be addressed in treatment.
(ii) Addressing body checking and avoidance

Patients are often not aware that they are engaging in body checking and that it is maintaining their body dissatisfaction. The ﬁ  rst step 
in addressing body checking involves obtaining a detailed account of the behaviour by asking patients to record it. An example moni-toring record is shown in Fig. 6.3.2.2.2. Patients are then helped to realize that body checking is not a helpful way of assessing their 
Day   ……Friday………..        Date  …..6th Sept ……….. 
Checking
(what done, time taken)Place
7.45
8.15
10.30
11.15
12.301.30
3.10
3.30
6.45
7.30
8.10
9.301 piece of toast with
butter and
marmite. 1 cup of tea 
1 apple & diet coke 
Cheese and tomato
sandwich & banana and kit
kat
Cup of coffee and 1
yoghurt
Water
Salad with tuna
1 glass of red wine
1 kit kat and half a
crunchie
1 glass of red wineKitchen
Office
Canteen
Office
Living
room
Living
room*
* VLooking at stomach and thighs
in bedroom mirror while
getting dressed (2 mins)

crunchie
Office
Canteen
Office
Living
room
Living
room*
Scrutinisng stomach in mirror
standing sideways (1 min)
Feeling and pinching stomach
while sitting at desk
(10mins)
Assessing shape of woman on
street (10secs)
Looking at reflection in
window while doing dishes
(5mins)
Touching and pinching stomach
and thighs while having a
bath (15mins)Bedroom
Office
toilet
Office
Office –
through
window
Kitchen
BathroomNot hungry but know I should have
breakfast  
Depressing. Can’t see any muscles –
only fat.
Ok
How can it be so fat?? Have hardly
eaten anything today!  
Chocolate was too much. Feel too full. 
myself sick.  
Fat disgusting flesh. Feel massive.  
Had planned to have other 1/ 2 of
chocolate bar. Can’t do it, am already
too fat!
Feel unhappy. Wish I was as thin as
her. Can’t accurately compare myself
to others – never really sure what my

too fat!
shape is. Frustrating.     
Still want more food but won’t let
myself since might lose control.   
I’m so huge! Wish I was tall and
elegant. How depressing.   
Feel disgusted. Am I ever going to get
rid of this fat?   
Feel fat! Too much chocolate today.
Have to get rid of the food. Go to bed
to stop thinking about it.    Time Food and drink consumed Place * V/L Context and comments 
Fig. 6.3.2.2.2 An adapted monitoring record illustrating body checking.6.3.2.2 cognitive behaviour therapy for eating disorders

SECTION 6  treatment methods in psychiatry 1302
shape or weight as it provides unreliable and biased information. 
Certain forms of body checking are best stopped altogether. In the case of more normative checking such as mirror use, education should stress that, as with other forms of body checking, what one ﬁ nds depends to an important extent upon how one looks (e.g. 
scrutiny of perceived ﬂ  aws tends to magnify them). For patients 
who avoid seeing their bodies, the therapist needs to explain that this too maintains dissatisfaction. Patients need to be encouraged to get used to the sight and feel of their body. Participation in activities that involve a degree of body exposure can be helpful, for example, swimming.
(iii) Addressing ‘feeling fat’

‘Feeling fat’ is an experience reported by many women but the intensity and frequency of this feeling appears to be far greater among people with eating disorders. Feeling fat is a target for treat-ment since it tends to be equated with being fat (irrespective of actual shape and weight) and hence maintains body dissatisfaction. Although this topic has received little research attention, clinical observation suggests that in many patients feeling fat is a result of mislabelling certain emotions and bodily experiences. It may be addressed by helping patients appreciate that feeling fat tends to be triggered by the occurrence of certain negative mood states (e.g. feeling bored or depressed) or by physical sensations that heighten body awareness (e.g. feeling full, bloated, or sweaty). Patients can then be encouraged to question the feeling when it occurs and correctly label and address the underlying triggering state using a problem-solving approach.

(iv) Developing marginalized domains for self-evaluation
Tackling the expressions of the over-evaluation of shape and weight 
will gradually reduce it. At the same time, it is also important to encourage the patient to increase the number and signiﬁ  cance of 
other domains for self-evaluation. Although this is an indirect means of diminishing the over-evaluation of shape and weight, it is nevertheless a powerful one.
(v) Exploring the origins of the over-evaluation
T owards the end of stage three it is often helpful to explore the origins of the patient’s sensitivity to shape, weight, and eating. An historical review can help to make sense of how the problem developed and evolved, highlight how it might have served a useful function in its early stages and help patients distance them-selves from the past. If a speciﬁ  c event appears to have played a

critical role in the development of the eating problem, the patient should be helped to reappraise this from the vantage point of the present.
(vi) Addressing dietary restraint
A major goal of treatment is to reduce, if not eliminate altogether, strict dieting. This dieting has two aspects: an attempt to limit eating termed ‘dietary restraint’ and actual under-eating in physio-logical terms termed ‘dietary restriction’ . ‘Regular eating’ will already have addressed one form of dietary restraint (delayed eating). Patients need to recognize that their multiple extreme and rigid dietary rules lead to preoccupation with food and eating, encourage binge eating and impose practical and social restrictions. 
It should therefore be agreed that dietary restraint needs to be addressed. T o do this, the patient’s various dietary rules should 
be identiﬁ  ed together with the beliefs which underlie them. The

be identiﬁ  ed together with the beliefs which underlie them. The 
patient should be helped to break the rules in order to test the beliefs in question and to learn that the feared consequences that 
maintain the dietary rule (typically sudden weight gain or binge eating) are not an inevitable result of breaking it. With patients who binge eat it is important to pay particular attention to food avoidance and to help them systematically reintroduce such foods into their diet.
(vii) Addressing event-triggered changes in eating

Among patients with eating disorders, eating habits may change in response to outside events. The change may involve eating less, stop eating altogether, overeating or binge eating. If these changes persist into stage three, they should be addressed by helping patients to tackle the triggering events using a problem-solving approach and by helping patients to accept the occurrence of intense-mood states and identify ways (that are not harmful) of modulating their moods.
(d) Stage four
The aims in stage four are to ensure that the changes made in treatment are maintained over the following months and that the risk of relapse is minimized in the long term. There are three appointments, each 2 weeks apart. During this stage, as part of their preparation for the future, pat ients discontinue self-monitor ing and 
transfer from in-session weighing to weighing themselves at home.

T o maximize the chances that progress is maintained the thera-
pist and patient jointly devise a speciﬁ  c plan for the patient to fol-
low over the following few months until a post-treatment review appointment. Typically this includes further work on body checking, food avoidance, and perhaps further practice at problem-solving. In addition, the therapist encourages patients to continue their efforts to develop new interests and activities.
There are two elements to ‘relapse prevention’ . First, patients 
must have realistic expectations regarding the future. A common 
problem is that many hope never to experience any eating 
difﬁ culties again. It needs to be explained that this makes them

difﬁ culties again. It needs to be explained that this makes them 
vulnerable to relapse since it encourages a negative reaction to even minor setbacks. Patients should be told to expect lapses with the eating problem continuing to be their Achilles’ heel. The goal is for patients to identify setbacks as early as possible, view them as a ‘lapse’ rather than a ‘relapse’ , and use a well-developed plan to deal with them. Thus, the second element of relapse prevention is the construction of such a plan. The therapist and patient should review the components of treatment with the aim of identifying the principles and procedures that were most relevant and helpful and devise a plan for the future incorporating this information.
Underweight patients

When treating patients who are underweight (most are cases of anorexia nervosa but some are cases of eating disorder NOS) three main modiﬁ  cations to the treatment are required: the motivation 
of these patients needs to be enhanced, their state of starvation needs to be corrected, and signiﬁ  cant others are more likely to be 
involved. As a result treatment needs to be considerably longer.
(a) Enhancing motivation to change
The poor motivation of these patients needs to be addressed from the outset of treatment. There are various ways of enhancing moti-vation
(17) including focusing on establishing a sound therapeutic 
relationship, ensuring that the patient feels understood, making it clear that one is working on behalf of the patient and not their

1303
relatives or concerned others, accepting the patient’s beliefs and 
values as genuine and comprehensible, and adopting an experi-mental approach in which the therapist and patient together explore the advantages and disadvantages of making changes. This includes educating the patient about the physiological and psycho-logical effects of starvation; for example, impaired concentration, preoccupation with food and eating, sleep disturbance, sensitivity to cold, ritualistic eating, social withdrawal, and enhanced fullness secondary to delayed gastric emptying.
(7) It is best to focus particu-

larly on those features that the patient views as a problem and explain how they tend to perpetuate the eating disorder. In addition, an exploration of the broader impact of the eating problem on the patient’s life is important. When exploring the advantages and dis-advantages of change, it is important to draw a distinction between the short-term and long-term consequences of change since patients tend to focus on the immediate present rather than the future.
(b) Restoring a healthy weight

Unless the weight loss is rapid or extreme, or the patient’s health is endangered by physical complications, weight restoration can usually be accomplished on an outpatient basis. Before focusing on weight gain, however, it is best to devote several sessions to establishing a collaborative working relationship and to developing a joint formulation and treatment plan. Thereafter, weight gain and the subsequent maintenance of a healthy weight must be an integral part of treatment. A target weight range should be identi-ﬁ ed in excess of a body mass index of 19.0.
The weight gain should be gradual and steady (at an average 
rate of about 0.5 kg/week). This requires an energy surplus to be established. This can be achieved by providing patients with energy-rich drinks to supplement their food intake (which should be increased such that it is sufﬁ  cient to maintain their current weight). 
The energy-rich drinks may be viewed as weight restorative

The energy-rich drinks may be viewed as weight restorative 
‘medicine’ designed to produce the energy surplus. The drinks should be phased out once the target weight range has been reached. Whilst regaining weight patients should be helped to address their shape and weight concerns and dieting in much the same way as described above. Once a satisfactory weight has been reached patients need time to learn how to maintain their weight in a normal manner.
(c) Involving the signiﬁ  cant others
Weight regain is a protracted process that takes considerable time 
and effort on the part  of the patient. If the patient lives with others it can be helpful to involve them if doing so is consistent with the nature of their relationship. Signiﬁ  cant others can help the patient 
choose what to eat and provide guidance concerning portion sizes. This is likely to be especially important with younger patients (many underweight patients are adolescents) who are still living at home with their parents.

We are grateful to the Wellcome Trust for its support. CGF holds a Principal Research Fellowship (046386). ZC and RM are supported by a programme grant (046386).Further information
Fairburn, C.G. (2008). Cognitive behavior therapy and eating disorders .
The International Journal of Eating Disorders .
 1. National Institute for Clinical Excellence. (2004). Eating disorders—core 
interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders . NICE Clinical Guideline 
No. 9. NICE, London. www.nice.org.uk
manual of mental disorders . American Psychiatric Association, 
 3. Fairburn, C.G. and Bohn, K. (2005). Eating disorder NOS (EDNOS): 
an example of the troublesome ‘not otherwise speciﬁ  ed’ (NOS) 
category in DSM-IV . Behaviour Research and Therapy ,43,
691–701.

3. Fairburn, C.G. and Bohn, K. (2005). Eating disorder NOS (EDNOS): 
691–701.
 4. Fairburn, C.G. and Harrison, P .J. (2003). Eating disorders. Lancet ,
 5. Fairburn, C.G., Cooper, Z., and Shafran, R. (2003). Cognitive behaviour 
therapy for eating disorders: a ‘transdiagnostic’ theory and treatment. 
Behaviour Research and Therapy ,41, 509–28.
 6. Fairburn, C.G. (1995). Overcoming binge eating , pp. 48–54. Guilford 
 7. Garner, D.M. (1997). Psychoeducational principles in treatment. 
In Handbook of treatment for eating disorders  (eds. D.M. Garner and 
P .E. Garﬁ  nkel), pp. 145–77. Guilford Press, New Y ork.
 8. Vitousek, K.M. (1996). The current status of cognitive–behavioral 
models of anorexia nervosa and bulimia nervosa. In Frontiers of 
cognitive therapy  (ed. P . Salkovskis), pp. 383–418. Guilford Press, 
New Y ork.

New Y ork.
 9. Polivy, J. and Herman, C.P . (1993). Etiology of binge eating: 
psychological mechanisms. In Binge eating: nature, assessment and 
treatment  (eds. C.G. Fairburn and G.T. Wilson), pp. 173–205. Guilford 
10. Fairburn, C.G., Jones, R., Peveler, R.C., et al.  (1993). Psychotherapy 
and bulimia nervosa: the longer–term effects of interpersonal 
psychotherapy, behaviour therapy and cognitive behaviour therapy. 
Archives of General Psychiatry ,50, 419–28.
11. Wilson, G.T., Fairburn, C.G., Agras, W.S., et al.  (2002). Cognitive-
behavioral therapy for bulimia nervosa: time course and mechanisms of change. Journal of Consulting and Clinical 
Psychology ,70, 267–74.
12. Fairburn, C.G., Peveler, R.C., Jones, R., et al.  (1993). Predictors of 
12–month outcome in bulimia nervosa and the inﬂ  uence of attitudes

12–month outcome in bulimia nervosa and the inﬂ  uence of attitudes 
to shape and weight. Journal of Consulting and Clinical Psychology ,
61, 696–8.
13. Fairburn, C.G., Stice, E., Cooper, Z., et al.  (2003). Understanding 
persistence in bulimia nervosa: a 5-year naturalistic study. Journal of 
Consulting and Clinical Psychology ,71, 103–9.
14. Fairburn, C.G. (2008). Cognitive behavior therapy and eating disorders .
15. Cooper, P .J. (1995). Bulimia nervosa and binge eating: a guide to 
recovery.  Robinson, London.
16. Schmidt, U. and Treasure, J. (1993). Getting better bit(e) by bit(e) .
Erlbaum, Hove.
17. Vitousek, K., Watson, S., and Wilson, G.T. (1998). Enhancing 
motivation for change in treatment–resistant eating disorders. Clinical
Psychology Review ,18, 391–420.6.3.2.2 cognitive behaviour therapy for eating disorders

SECTION 6  treatment methods in psychiatry 1304
6.3.2.3 Cognitive behaviour therapy 
This chapter describes A.T. Beck’s cognitive behaviour therapy 
(CBT) for depression.(1) Beck’s is probably the most fully 
developed, comprehensively evaluated, and widely disseminated cognitive behavioural approach to depression. Additionally, CBT is an effective treatment for a range of acute psychiatric disorders, shows promise for severe mental illness and personality disorder, and is thus helpful not only with primary depression, but also with a range of comorbid conditions.
Central characteristics of CBT
The general principles and nature of CBT are described elsewhere. Two speciﬁ  c points relate to depression:
(a) Demands of CBT
Given the nature of depression, CBT challenges both therapist and 
patient. It requires active engagement  (e.g. willingness to carry out

patient. It requires active engagement  (e.g. willingness to carry out 
self-help assignments), yet depressed patients often lack motiva-tion and energy. It is based on a friendly collaboration , yet 
depressed people often ﬁ  nd it hard to talk and clinicians may ﬁ  nd 
their negativity aversive. It is an educational approach , using writ-
ten materials and record sheets, yet depressed patients often have concentration and memory difﬁ  culties. Its stance is optimistic , yet 
depressed patients are often afraid (or convinced) that change is impossible. Therapists should be alert to these difﬁ  culties, under-
stand them as aspects of depression rather than blaming the patient (‘She must want to be depressed’) or themselves (‘I’m no good at this’), and maintain a persistent, problem-solving stance.
(b) Advantages of CBT

Nonetheless, CBT has real advantages for depressed patients. Its structure  discourages rumination, and helps patients to focus sys-
tematically on their difﬁ  culties. Its emphasis on a warm therapeu-
tic relationship  encourages empathy, while its goal orientation
implies that change is possible. The coherent model  of human 
functioning, on which it is based, allows it to address many issues, including depression itself, comorbid conditions, problems in liv-ing, long-standing difﬁ  culties (such as low self-esteem), patients’ 
responses to therapy and therapist, and therapists’ responses to patients. Its emphasis on collaboration and on transfer of knowl-
edge and skill  empowers patients to become their own therapists 
and to take control of their lives.
Beck’s interest in the role of cognition grew out of his practice as a psychoanalytical therapist. Dissatisﬁ  ed with analytical understand-

ings of depression, he became curious about the role of the nega-
tive thinking he observed in depressed patients.
(2–4) Beck’s clinical 
observation and research consistently showed the thinking of depressed people to be dominated by self-derogation, negative expectations, overwhelming problems and responsibilities, depri-vation and loss, and escapist and suicidal wishes, themes fuelled by systematic biases in information processing. He suggested that 
patients could recover from depression by learning to re-evaluate everyday cognitions, and to understand the long-standing idiosyn-cratic schemas under lying them.
This early scientist–practitioner stance has remained central 
CBT, stimulating an integrated ﬂ  ow of experimental investigation,

CBT, stimulating an integrated ﬂ  ow of experimental investigation, 
practice development, and research into treatment efﬁ  cacy, which 
has continued to the present day. The ﬁ  rst successful outcome trial 
of CBT for depression appeared in 1977.
(5) A detailed treatment 
manual emerged shortly afterwards.(1) Thirty years of randomized 
controlled trials now support the treatment’s effectiveness.(6) Like 
other short-term focused psychological treatments, it has consis-tently proved as effective as antidepressant medication post-treat-ment. It reduces the likelihood of relapse by about 50 per cent, and this effect endures,
(7) and can be enhanced by booster sessions in 
the months following treatment.(8) Thus CBT emerges as surpris-
ingly cost-effective.(9) With adequate training and supervision 
equivalent results can be achieved even with severe depression and high comorbidity.
(10, 11)
Technique

(10, 11)
Technique
Cognitive case conceptualization
(a) Enduring cognitive vulnerability to depression
The cognitive model of depression  proposes that enduring cogni-
tive structures and processes shape how everyday experience is interpreted, and are in turn reinforced by these interpretations. This model (Fig. 6.3.2.3.1) forms the basis for an individualized 
conceptualization , developed and shared with the patient, which 
informs and guides therapy. It suggests that experience  (loss, events 
with lasting implications for self-worth)
(12,13)  leads people to reach 
fundamental conclusions  about themselves, others, and the world 
(‘basic’ or ‘core’ beliefs, or schemas). They devise guidelines for 
living  (‘conditional assumptions’), which allow them to operate in

living  (‘conditional assumptions’), which allow them to operate in 
the world, assuming the truth of those conclusions. Using schemas and rules to organize experience and guide behaviour is a normal part of human functioning. However, where schemas are globally negative (e.g. ‘I am inferior’) and assumptions extreme and resis-tant to change (e.g. stringent perfectionism), they become counter-productive. Evidence for cognitive vulnerability  to depression 
prior to ﬁ  rst onset is now emerging,
(14) as is evidence that recur-
rent episodes leave an tendency to re-experience depressogenic processing patterns in the presence of mild, normal depressed mood (‘cognitive reactivity’).
(15, 16)
(i) Relationship between thinking and other aspects of depression
Dysfunctional beliefs and assumptions are activated by events  that

(15, 16)
Dysfunctional beliefs and assumptions are activated by events  that 
match the person’s particular sensitivities. So a person with nega-tive beliefs about the self whose psychological well-being depends on love and approval might become depressed after experiencing rejection. Activation of the system results in an upsurge of ‘ nega-
tive automatic thoughts ’—‘negative’ in that they are associated 
with painful emotions, and ‘automatic’ in that they pop into the person’s mind rather than being a product of reasoned reﬂ  ection. 
Such thoughts reﬂ  ect processing biases  such as overgeneralization. 
Depression is characterized by biased negative thoughts about the self (e.g. ‘I’m useless’), the world (e.g. ‘My situation is intolerable’), and the future (e.g. ‘Nothing will ever change’). The latter (hope-lessness) is central to suicidality.

1305
The more depressed people become, the more negative thoughts 
they think, and the more they believe them. The more negative 
thoughts they think and the more they believe them, the more 
depressed they become. Thus depression is maintained by vicious 
circles  in which negative thinking and other symptoms reinforce 
one another. Experimental and clinical research reﬂ  ects this recip-
rocal relationship between affect and cognition : modifying 
depressive thinking modiﬁ  es depressed mood, while modifying 
depressed mood modiﬁ  es depressive thinking.
(ii) Objectives of CBT for depression
The ﬁ  rst goal is to break the vicious circle  described above by 
teaching patients to work effectively with negative automatic 
thoughts. Attention then turns to cognitive predisposing factors 
(beliefs, assumptions) in order to reduce vulnerability  and decrease 
the likelihood of future episodes. The aim is not to teach realistic

the likelihood of future episodes. The aim is not to teach realistic 
thinking per se , but rather to help patients to resolve their problems 
by teaching them cognitive behavioural skills.
(iii) Overview of CBT for depression
Treatment usually proceeds through the following stages :
◆ diagnosis, assessment, problem identiﬁ  cation
◆ cognitive interventions designed to reduce the frequency of 
negative thoughts◆ behavioural assignments intended to tackle behavioural and 
motivational deﬁ  cits
◆ monitoring, questioning, and testing negative automatic 
thoughts (the main body of therapy)
◆ relapse prevention.
Patients usually move from one stage to the next as each is mas-
tered. The starting point varies : severely depressed patients often 
begin with simple behavioural interventions, whereas relatively 
mild depressions may immediately be amenable to cognitive work.

mild depressions may immediately be amenable to cognitive work. 
At each stage, cognitive and behavioural interventions are closely 
integrated .(17) Thus behavioural interventions such as activity 
scheduling present opportunities to identify, question, and test 
negative thoughts, while work on thoughts and assumptions is 
closely linked to changes in behaviour.
Traditionally, up to 20 sessions  of therapy are offered, twice 
weekly for 4 weeks and once weekly thereafter. Most patients 
respond within about 15 sessions. Some do well with 4–6 sessions, 
but severe chronic depressions may require more than 20 sessions, 
as well as shorter, more frequent sessions early on. Post-treatment 
boosters help to increase conﬁ  dence and consolidate and extend 
skill. Sessions start with agenda-setting (prioritizing what to work

skill. Sessions start with agenda-setting (prioritizing what to work 
on), homework review, and feedback on the previous session. After 
the day’s main topics have been discussed, more homework practice 
is agreed to ensure generalization and reinforce new learning. Key 
points are summarized, and the therapist asks for reactions to the 
session, including anything that has been uncomfortable or unclear.
CBT was developed as a treatment for moderate-to-severe uni polar 
depression,(1) and has been consistently effective with this population. 
However, good average results in outcome trials conceal wide vari-
ations in responsiveness.(18) Consistent predictors of treatment 
response remain elusive.
Patients presenting with endogenous symptoms are as likely to 
respond well as non-endogenous patients. However, results for 
severe depression(19) and bipolar disorder(20) remain somewhat

severe depression(19) and bipolar disorder(20) remain somewhat 
conﬂ  icting.
Some factors may facilitate a positive response; well-developed 
pre-existing cognitive and behavioural coping skills, acceptance of 
the cognitive model, willingness to engage in self-help assignments, 
an early focus on teaching speciﬁ  c cognitive-therapy skills, ease of 
access to thoughts and feelings, problem speciﬁ  city, and ability 
to form a collaborative alliance. Such criteria can be explored at 
assessment, especially if it is divided into two sessions with a simple 
intervening homework assignment.
Patients who are unsuitable for short-term CBT(21) may none-
theless respond to a modiﬁ  ed approach with:
◆ greater emphasis on socialization and on cultivating a solid 
working relationship
◆ more extended behavioural work

◆ more work on enduring depressogenic schemas in the later 
stages of treatment
◆ more emphasis on integration with antidepressant medication
◆ more careful attention to environmental factors (including not 
only life stresses and family relationships, but also the ward and 
health-care team)
Fig. 6.3.2.3.1 Cognitive model of depression.6.3.2.3 cognitive behaviour therapy for depressive disorders

SECTION 6  treatment methods in psychiatry 1306
Finally, given that CBT and antidepressant medication generally 
produce similar results, the patients’ wish for psychological treat-ment should also be taken into account.
Selection procedure
Diagnosis: recognizing and labelling depression
CBT was designed for moderate-to-severe major unipolar depression. The diagnostic criteria for major depressive episode,
(22) remark-

ably consistent for over 30 years, describe a symptom pattern (including cognitive features) that has been recognized throughout history, and appears basically consistent across age, gender, race, and culture. However, the relative emphasis on different symptoms and the manner in which distress is expressed varies, and assess-ment procedures should be adapted to explore cultural context. Additionally, sociocultural factors necessarily influence belief systems, and therapists should be sensitive to such differences, rather than assuming that their own assumptions are shared by their patients.
Severity

Severity
Severity should be taken into account when deciding whether con-current (or alternative) physical treatments or hospitalization are necessary, and in determining where to begin within CBT. Severity can be assessed through clinical interview (e.g. intensity, pervasive-ness, and reactivity of depressed mood; extent of behavioural and interpersonal deﬁ  cits). The Beck Depression Inventory  (BDI-
II)
(23) a well-established self-report measure of depression, pro-
vides a rapid overview of symptoms. Weekly completion allows clinicians to observe overall progress, as well as tracking scores on particular items, e.g. hopelessness. Hopelessness and suicidality should be routinely assessed
(24) and any sign of suicide risk investi-
gated in-depth.(25)
Clinical interview
Interview assessment for CBT includes the following:
(a) Symptoms and associated cognitions

Negative automatic thoughts both trigger and enhance symptoms of depression (Table 6.3.2.3.1). Identifying meanings attached to symptoms prepares the ground for more helpful perspectives (e.g. ‘These are symptoms of depression, not a reﬂ  ection of my 
worth as a person’).
(b) Impact on functioning
It is important to establish how depression affects relationships, work performance, and leisure time. It may be necessary to take practical steps to improve the patient’s situation (e.g. gradual reintroduction to work).
(c) Coping strategies

The more depressed the patient, the more likely that she/he has adopted coping strategies which help in the short-term, but are in the longer-term self-defeating (e.g. alcohol or drugs, social with-drawal, bed). Therapist and patient can discuss the pros and cons of these, and how cognitive behavioural strategies might be more beneﬁ  cial. The aim is for patients to reach the point of trying more 
adaptive coping strategies for themselves.(d) Onset of current episode

Information about the onset of episodes may provide valuable clues about beliefs and assumptions. For example, a young woman became depressed when her husband took a job abroad, and was away for long periods. She believed that he would not have done so if he truly loved her. In fact, he had taken the job because it paid exceptionally well and the savings they could make would allow them to start the family they had been planning. The therapist noted the patient’s interpretation of her husband’s behaviour, and later in therapy used this clue as a starting point to identify long-standing doubts about her attractiveness, and a linked dysfunc-tional assumption: ‘If someone is not there for me all the time, it means they don’t care about me’ .
(e) Background
(i) Previous treatment

Many depressed patients presenting for CBT have already received other treatment (most commonly antidepressant medication and counselling). The therapist should inquire about the outcome  of 
such treatment, and what the patient makes of it . Depressed 
patients often conclude that the incomplete success of prior treat-ment means that they will also be unable to beneﬁ  t from this new 
approach. Such thoughts can be worked with using straightforward cognitive behavioural methods (identify, question, test). When the patient has received psychological therapy, it is often helpful to ask what they learned  from it. If they feel they learned nothing, 
this may predispose them to approach CBT with pessimism.Table  6.3.2.3.1  Negative automatic thoughts and symptoms of 
Symptoms Negative automatic thoughts
Behavioural
Lowered activity level I can’t do it. It won’t work.Procrastination I’ll never get it done. It’s too much for me.

Motivationa l
Loss of energy It’s too much effort. I’ll wait till I fell better.Loss of pleasure, interest I won’t enjoy it. What’s the point? I can’t be 
bothered.
Affective
Sadness I’ve lost everything important to me.Guilt I’m letting everybody down.Anger Why can’t people just leave me alone?
Shame What must everyone think?
Anxiety I’m not going to be able to cope.
Cognitive
Indecisiveness Whatever I do will go wrong.Poor concentration I must be going senile.
Physical
Loss of sleep If this goes on, I won’t be able to function.Loss of appetite I’m going to make myself ill.Loss of sexual appetite Our marriage is at an end.
Other
Suicide This is unbearable. There is no other way out.
Problems in living There’s nothing to be done.

1307
Alternatively, if they learned something of value, CBT can build on 
this positive experience.
(ii) Expectations of CBT
These may reﬂ  ect general pessimism about change, especially if 
patients know nothing about the approach. Those who have heard or read about CBT, and are aware of outcome data, may be more optimistic, although still anxious lest it fail to help them . Others 
may have heard negative reports (e.g. that it is mechanistic and fails to address deep issues). Non-defensive discussion  of expectations 
allows doubts and misconceptions to be addressed, as well as encouraging open-mindedness and continued frank feedback from the patient.
(iii) Early experience and resultant beliefs and assumptions
CBT is conceptualization driven ,(26)closely based on the 
cognitive model of depression . In order for patients to understand 
how their problems developed, and that current beliefs are learned opinions rather than reﬂ  ections of fact, it is helpful to

how their problems developed, and that current beliefs are learned opinions rather than reﬂ  ections of fact, it is helpful to 
know about relevant formative experiences. This is particularly true when working with severe, chronic problems, and personality disorders. However, obtaining historical information is often 
not an immediate priority . It is more important initially to convey 
the hopeful message that something can be done to change things for the better. Therefore details about history, beliefs, and assump-tions may not be explored until work on behavioural deﬁ  cits 
and negative automatic thoughts has produced a reduction in hopelessness and depressed mood. That said, where patients are relatively mildly depressed, psychologically minded, and able to articulate their difﬁ  culties with ease, a draft conceptualization

incorporating historical information, beliefs, and assumptions sometimes emerges even from the initial assessment.
Managing treatment
(a) Starting treatment
The ﬁ rst treatment interview has four main objectives :
◆ to establish a warm, collaborative therapeutic alliance
◆ to list speciﬁ  c problems and  associated goals , and select a ﬁ  rst 
problem to tackle
◆ to educate the patient about the cognitive model , especially the 
vicious circle that maintains depression
◆ to give the patient ﬁ  rst-hand experience of the focused, work-
man-like, empirical style  of CBT.
These convey two important messages: (1) it is possible to make 
sense of depression; (2) there is something the patient can do about it. These messages directly address hopelessness and helplessness.
(i) Identifying problems and goals
The problem list  usually includes symptoms of depression. It may

The problem list  usually includes symptoms of depression. It may 
also contain aspects of other disorders (e.g. panic attacks), problems in living (e.g. family conﬂ  icts), and, in some cases, long-
standing psychological problems (e.g. fear of intimacy). Developing the list provides the therapist with a ‘map of the territory’ , which suggests possible targets for intervention, as well as an opportunity to foster the therapeutic relationship by demonstrating empathy. It suggests that apparently chaotic experience can be broken down into manageable problem areas. Goal identiﬁ  cation  then implies 
that progress is possible.(ii) Introducing the cognitive model of depression
The therapist’s next task is to demonstrate how negative thinking 
inﬂ uences emotion and behaviour , relating this to the patient’s

inﬂ uences emotion and behaviour , relating this to the patient’s 
experience using material derived from the session. The therapist explains that the patient will learn to notice negative automatic thoughts, to stand back, question them, and develop more realistic and helpful perspectives. Patients are often doubtful about their ability to do this. It is important therefore to present CBT as a 
learning opportunity  during which skills can be acquired, step by 
step, with the therapist’s guidance. The therapist is not obliged to convince patients that CBT will work for them, but a willingness to try it in practice is essential.
(iii) Where to start?
Aﬁ rst treatment target  is chosen towards the end of the ﬁ  rst 
session, and an appropriate homework  task agreed upon. Suitable

session, and an appropriate homework  task agreed upon. Suitable 
homework tasks include: observing a recording of the session and noting important points (this assignment follows every session), reading assignments,
(27) and self-monitoring assignments. The 
initial target varies. Where patients are only relatively mildly depressed, and remain active and capable of experiencing interest and pleasure, monitoring negative automatic thoughts can begin right away. Where the depression is more severe, with signiﬁ  cant 
behavioural and motivational deﬁ  cits, it is best to begin with 
behavioural interventions.
(b) Behavioural interventions
(i) Reducing rumination
In severe depression, access to more positive perspectives may be blocked by depressed mood, making modifying negative automatic thoughts difﬁ  cult or impossible. At the same time, depressed

In severe depression, access to more positive perspectives may be blocked by depressed mood, making modifying negative automatic thoughts difﬁ  cult or impossible. At the same time, depressed 
patients spend a great deal of time ruminating about their difﬁ  cul-
ties and shortcomings.
(28) Learning to direct attention elsewhere
reduces the frequency of negative thoughts and hence improves mood. This palliative measure will not resolve the patient’s prob-lems, but its impact reinforces the model, and feeling somewhat better can facilitate more constructive thinking.
(ii) Monitoring activities
Lowered activity levels and loss of interest and pleasure are often central to depression, and interventions designed to address them are known to be powerful in their own right.
(19) Early behavioural 
interventions serve to maximize engagement in activities provid-
ing a sense of pleasure and mastery . This has a direct impact on

ing a sense of pleasure and mastery . This has a direct impact on 
mood, and provides opportunities to test negative thoughts that block engagement and, in a more global sense, prevent recovery (e.g. ‘I can’t do anything to change how I feel’).
Patients record what they do, hour by hour, on a Weekly Activity 
Schedule (Fig. 6.3.2.3.2). Each activity is rated 0–10 for Pleasure 
(P) and Mastery (M) . P ratings indicate how enjoyable the activity 
was, and M ratings how much of an achievement it was. ‘P’ is usu-ally easily understood, but M can present difﬁ  culties. Depressed 
people often feel that nothing they do is an achievement, perhaps because most of their activities are routine (‘What’s so special about that?’) or do not meet their standards (‘I should have done more’). 
M should therefore be explained as ‘an achievement, given how you

M should therefore be explained as ‘an achievement, given how you 
felt at the time ’ . Thus even simple activities (e.g. making a cup of 
tea) are real achievements when patients are hampered by low mood and loss of energy. Ratings should be made immediately 6.3.2.3 cognitive behaviour therapy for depressive disorders

SECTION 6  treatment methods in psychiatry 1308
after each activity, since retrospective ratings may be distorted by 
negatively biased recall. In addition, it is helpful for patients to 
review each day , asking questions like: ‘What worked for me?’ 
‘What did not work?’ ‘What do I need more of? Less of? Different?’
(iii) Planning activities
Once self-monitoring is mastered, each day is planned in advance
on an hour-by-hour basis. This:
◆ provides a structure and helps with setting priorities
◆ averts the need to keep making decisions about what to do next
◆ reduces what may seem like chaos to a manageable list
◆ increases the chances that activities will be carried out
◆ enhances patients’ sense of control.
A pattern of activities is sought in which mastery and pleasure 
are balanced and maximized . The plan is likely to contain a blend 
of obligations (e.g. the ironing) and pleasures (e.g. listening to 
music). Avoided tasks can be included, broken down into manage-

able steps (‘graded task assignment’). Again, it is helpful for patients 
to review each day in detail, identifying unhelpful thoughts to be 
worked on in the next therapy session (e.g. ‘If I can’t complete the 
task, I might as well not bother at all’). Thus the cognitive element 
is present even when behaviour change is the primary target.
(c) Working with negative automatic thoughts
Once behavioural methods have been mastered, patients learn to 
identify, question, and test negative automatic thoughts . The main tool here is the Dysfunctional Thoughts Record (Fig. 6.3.2.3.3). 
The example summarizes a lengthy discussion that took place 
when a patient experienced a serious setback midway through 
(i) Identifying negative automatic thoughts

Patients learn to record upsetting incidents  as soon as possible 
after they occur (delay makes it difﬁ  cult to recall thoughts and 
feelings accurately). They learn:
1T o identify unpleasant emotions  (e.g. despair, anger, guilt), 
signs that negative thinking is present. Emotions are rated for 
intensity on a 0 to 100 scale. These ratings (though the patient 
may initially ﬁ  nd them difﬁ  cult) help to make small changes in 
emotional state obvious when the search for alternatives to nega-
tive thoughts begins. This is important, since change is rarely 
all-or-nothing and small improvements may otherwise be 
missed.
2T o identify the problem situation . What was the patient doing 
or thinking about when the painful emotion occurred (e.g. ‘wait-
ing at the supermarket checkout’ , ‘worrying about my husband

ing at the supermarket checkout’ , ‘worrying about my husband 
being late home’)?
3T o identify negative automatic thoughts associated with the 
unpleasant emotions . Sessions direct the therapist towards ask-
ing: ‘And what went through your mind at that moment?’ Patients 
become aware of thoughts, images, or implicit meanings that 
are present when emotional shifts occur, and record them word-
for-word. Belief in each thought is also rated on a 0 to 100 per cent 
Fig. 6.3.2.3.2 Weekly activity schedule. P , pleasure; M, mastery.

1309
scale (100 per cent represents complete belief, 50 per cent a mod-
erate degree of belief, and so on). Again, this helps to make small 
changes in conviction evident at the next stage.
The skill of identifying painful emotions and associated thoughts 
is best learned if therapist and patient work through examples on 
the sheet  before the patient self-monitors independently. Therapists 
can make sure that patients understand what is required, and are 
prepared for possible difﬁ  culties. For example, patients sometimes 
avoid recording thoughts because doing so is upsetting. Therapists 
can reassure them that this phase will pass once they learn to answer 
their thoughts, and suggest that they follow recording by engaging 
in an absorbing and pleasurable activity. Sometimes thoughts 
recorded do not seem to ‘ﬁ  t’ the emotion experienced; in this case, 
therapists may need to help patients to ‘unpack’ the meaning of

therapists may need to help patients to ‘unpack’ the meaning of 
the thought  (for example, ‘That didn’t go too well’ may turn out to 
mean ‘I’m a total failure’). Time taken to learn accurate self-
monitoring varies; many patients acquire the skill within a few 
days, but others take much time and coaching.
(ii) Questioning negative automatic thoughts
Once patients can record thoughts and feelings, they learn to search 
for alternative views , writing these in the ﬁ  fth column of the 
Dysfunctional Thoughts Record. There is no such thing as a ‘right’ 
answer to a negative thought; the ‘right’ answer is the one that helps 
the patient to feel better and handle the situation more constructively. Accordingly, the therapist’s task is not to suggest alternatives, but 
rather to elicit them through ‘ guided discovery ’ , a process of sensi-

tive questioning, which allows patients to reach new interpretations 
independently. It is helpful for therapists to develop a personal 
‘library’ of questions, through discussion with colleagues, observa-
tion of other therapists, attendance at workshops, and reading. 
Productive areas of inquiry include:
1What is the evidence?  Processing biases in depression mean that 
patients give weight to information consistent with prevailing 
perspectives at the expense of information, which suggests 
that they may not be wholly true. The therapist thus needs to 
examine ‘evidence’ believed to support the thought, and also to 
seek information that might contradict it.
2What alternative views are there?  Questions such as the follow-
ing can prompt alternative perspectives: ‘How would you have 
reacted to this before you became depressed?’ ‘What is your per-

spective on this when you feel relatively well?’ ‘What might some-
one whose views you trusted make of this?’ ‘If someone you cared 
about came to you with this problem, what would you say?’
3What are the advantages and disadvantages of this way of 
thinking?  This approach is particularly helpful with self-critical 
thinking. Patients often believe that self-criticism is an effective 
way of bringing about change; in fact, it only intensiﬁ  es depres-
sion. Patients who habitually self-criticize can be helped to draw 
Fig. 6.3.2.3.3 Dysfunctional thoughts record.6.3.2.3 cognitive behaviour therapy for depressive disorders

SECTION 6  treatment methods in psychiatry 1310
up an analysis of pros and cons. Apparent advantages (e.g. ‘It 
keeps me on my toes’) may in fact be outweighed by disadvan-tages (e.g. ‘It paralyses me’).
4What are the biases in my thinking?  The tendency to make 
inferential errors such as overgeneralization has already been mentioned. Learning to recognize these can be helpful, especially when patients regularly make the same mistake.
Alternatives reached by questioning negative automatic thoughts 
are recorded on the Dysfunctional Thoughts Record. The patient rates them for degree of belief, to ensure that they are sufﬁ  ciently
convincing (they do not require belief ratings of 100 per cent). If alternatives are not at all convincing, they will have no impact on the strength of the original automatic thoughts or associated emotions. These are now re-rated in the ﬁ  nal column as a check 
that plausible alternatives have been found.

As with self-monitoring, these skills are best learned by working 
through examples in session  before the patient attempts to 
answer thoughts independently. Even then, patients are sometimes unable to ﬁ  nd alternatives, especially if emotion is high. This is 
quite normal, given that questioning one’s thoughts is a complex skill. It may be helpful to leave searching for alternatives until the storm is past. Sometimes alternatives make no difference to the original thoughts or emotions. This may be because the patient has reservations about their validity (‘Y es, but . . . ’), which can dealt with like other negative thoughts. Alternatively, it may be that non-verbal methods (e.g. imagery work, experiential learning) are nec-essary to facilitate emotional change, or that the resistant thought is a more or less direct statement of an underlying belief of much longer duration, which will take longer to change.

(iii) Testing negative automatic thoughts: what can I do now?
It is important that cognitive changes brought about by question-ing are consolidated through behavioural experiments .
(17) These 
are often designed to test out the validity of the new perspective by seeking further information or acting differently and observing the results. They may also include practical plans to solve genuine life problems and to deal with the trigger situation differently should it occur again.
(d) Ending treatment
Although most episodes of depression are time-limited, relapse 
and recurrence are common —the more so, the more episodes a 
person has experienced. CBT therefore emphasizes working on cognitive vulnerability factors, summarizing and consolidating learning, and preparing for possible setbacks. A new approach, Mindfulness-Based Cognitive Therapy ,
(29) which integrates elements

(29) which integrates elements 
of CBT with intensive meditation practice, has been developed speciﬁ  cally to tackle this problem. Its effectiveness with patients 
who have experienced three or more episodes of depression has been demonstrated in two clinical outcome trials.
(30, 31)
(i) Re-evaluating dysfunctional assumptions
Once patients are skilled at answering negative automatic thoughts, attention turns to dysfunctional assumptions that make them vulnerable to depression. Often these emerge from information gathered earlier, for example repeating themes in Dysfunctional Thoughts Records. They may also be identiﬁ  ed using a ‘downward 
arrow’ technique, which involves identifying situations that typically distress the patient, and associated thoughts. Instead of responding directly to these, the therapist asks: ‘If that was

arrow’ technique, which involves identifying situations that typically distress the patient, and associated thoughts. Instead of responding directly to these, the therapist asks: ‘If that was 
true, what would it mean to you?’ This question (or variants) is repeated until a general assumption or rule, relevant to a range of situations, emerges. The validity of the rule is then questioned and tested. This process normally takes several sessions to com-plete. A helpful sequence of questions is given below (these are not exhaustive:
1Where did this rule come from?  Identifying the source of a 
dysfunctional assumption (e.g. parental criticism) often helps to encourage distance by suggesting that its development is under-standable, though it may no longer be relevant or useful.
2In what ways is the rule unrealistic?  Dysfunctional assumptions 
do not ﬁ  t the way the world works. They operate by extremes, 
which are reﬂ  ected in their language (always/never rather than

which are reﬂ  ected in their language (always/never rather than 
some of the time; must/should/ought rather than want/prefer/would like).
3In what ways is the rule helpful?  Dysfunctional assumptions are 
not usually wholly negative in their effects. For example, perfec-tionism may lead to genuine high-quality performance. If such advantages are not recognized and taken into account when new assumptions are formulated, the patient may be reluctant to move forward.
4In what ways is the rule unhelpful?  The advantages of 
dysfunctional assumptions are normally outweighed by their costs. Perfectionism leads to rewards, but it also undermines satisfaction with achievements and stops people learning from constructive criticism.
5What alternative rule might be more realistic and helpful?

Once the old assumption has been undermined, it is helpful to formulate an explicit alternative (e.g. ‘It is good to do things well, but I am only human-sometimes I make mistakes’). This provides a new guideline for living, rather than simply under-mining the old system.
6What needs to be done to consolidate the new rule?  As with 
negative automatic thoughts, re-evaluation is best made real through experience: behavioural experiments. These encourage patients to challenge speciﬁ  c examples of old rules, as well as 
testing out the validity of new ones by acting as if they were true and observing the results This systematic work may need to con-tinue for weeks or indeed months, given that assumptions have often been in place for many years.
(ii) Re-evaluating negative core beliefs
Negative thoughts often disappear as patients recover, whether the

Negative thoughts often disappear as patients recover, whether the 
depression is treated by psychological means or not. Sometimes, however, they reﬂ  ect enduring beliefs about the self, the world 
(including other people), or the future, which if left untouched may predispose the patient to become depressed again. Methods for dealing with these have primarily been developed in the context of CBT for personality disorder,
(32, 33)  but can often be used within 
short-term CBT. This is important, given limited resources.
The cognitive model suggests that negative beliefs contributing 
to vulnerability to depression are (like dysfunctional assumptions) based on early learning, and maintained by a consistent bias in favour of information, which conﬁ  rms them, and against infor-
mation, which contradicts them. Therapists help patients to become aware of this bias, to question the ‘evidence’ that upholds

1311
the negative beliefs (much as the ‘evidence’ in favour of negative 
automatic thoughts is questioned), and to search actively for information which contradicts it. Once a relevant belief has been identiﬁ  ed (e.g. ‘I am no good’) and rated for degree of belief 
(0–100 per cent), the suggestion is introduced that this may be more of an opinion than a fact (work at the level of automatic thoughts should have prepared the ground for this idea). If possi-ble, the patient is asked to suggest a more positive alternative (e.g. ‘If you were not ‘no good’ , how would you like to be?’), and belief in the alternative (which is likely to be low) is also rated. The alterna-tive provides a new ‘address’ at which to store information incon-sistent with the old belief. However, it is not always possible to ﬁ  nd

one at this stage (e.g. when the patient has predicated his or her life on the belief and accumulated a large body of supporting evidence). In this case, an alternative may only become available once the old belief has been systematically weakened.
Supporting ‘evidence’ may include events from the distant past,

Supporting ‘evidence’ may include events from the distant past, 
which have been interpreted in a self-derogatory way (e.g. child-hood abuse), as well as later experiences (e.g. a broken marriage) and everyday events of the kind already recorded on the Dysfunctional Thoughts Record. Each item is questioned, and new and more adaptive interpretations arrived at. In addition, patients are asked to record evidence that would support a more positive alternative to the old belief (e.g. examples of their strengths and skills). The success of these interventions is assessed by repeatedly rating the degree of belief in the old system, as well as in the new alternatives. This work too may take a considerable time, especially if negative beliefs have had a sizeable impact on the person’s life. Where treatment time is limited for practical reasons, clinicians may ﬁ nd it helpful to space out later sessions, ensuring that intervening 
weeks are used to consolidate and extend within-session work.

(iii) Consolidating learning: ‘blueprints’
Preparation for ending treatment begins with the treatment 
contract. The implication of offering a limited number of sessions is that treatment will end, and that patients will acquire the skills necessary to deal with depression independently. Throughout therapy, they are encouraged to take increasing responsibility for determining session content, making practical suggestions, devis-ing homework assignments, summarizing learning, and applying new skills in fresh areas. Written session summaries and therapy tapes encourage reﬂ  ection and consolidation.
At the end of treatment, gains are summarized in a personal 
action plan or ‘blueprint for the future’ . The blueprint is conﬁ  ned

action plan or ‘blueprint for the future’ . The blueprint is conﬁ  ned 
to one or two sheets of paper, guides continued learning, and helps deal with relapse or recurrence. It draws on the case conceptualiza-tion, session notes, homework records, reading materials, and the 
like. The therapist should examine sessions, records, etc. indepen-
dently, so that the plan is drawn up jointly, nothing important is forgotten, and the patient goes away with as full a summary as possible. The following questions provide a useful framework:
1How did my problems develop?  (unhelpful beliefs and 
assumptions, the experiences that led to their formation, events precipitating onset)
2What kept them going?  (maintenance factors)
3What did I learn from therapy that helped?  (techniques (e.g. 
activity scheduling) and ideas (e.g. ‘I can do something to inﬂ  u-

ence my mood’). T echniques should be detailed so that patients know exactly what to do should depression recur. Examples of 
handouts and record sheets can be included.)
4What were my most unhelpful negative thoughts and assump-
tions? What alternatives did I ﬁ  nd to them?  (summarized in 
two columns)
5How can I build on what I have learned?  (a solid, practical, 
clearly speciﬁ  ed action plan)
(iv) Preparation for setbacks
The blueprint should also be used to plan for relapse. It is helpful

The blueprint should also be used to plan for relapse. It is helpful 
right at the beginning of treatment to tell patients that, however well they do, they may well experience a setback at some point, not least because periods of low mood are a normal part of human experience. CBT will not prevent the patient from ever having another moment’s distress; it will provide tools for dealing with dis-tress more effectively. This information can help patients to respond with less fear and despair when they do encounter setbacks.
Preparation for setbacks can be framed by the following questions:
1What might lead to a setback for me?  For example, future losses 
(e.g. children leaving home) and stresses (e.g. ﬁ  nancial difﬁ  cul-
ties), i.e. events which impinge on patients’ vulnerabilities and 
are thus liable to be interpreted negatively. For people who have

are thus liable to be interpreted negatively. For people who have 
experienced recurrent depression, mild normal low mood (with-out any major environmental stimulus) can act as a trigger for negative thinking which, if unchecked, can spiral down into clinical depression.
2What early warning signs do I need to be alert for?  Feelings, 
behaviours, and symptoms that might indicate the beginning of another depression are identiﬁ  ed and listed, using careful 
analysis of this and previous episodes and of ﬂ  uctuations in 
mood occurring during treatment.
3If I notice that I am becoming depressed again, what should 
I do?  Clear simple instructions, which will make sense despite 
low mood, are needed here. Speciﬁ  c ideas and techniques sum-

marized earlier in the blueprint should be referred to. General encouragement can also be included (e.g. ‘Don’t panic’), as well as a speciﬁ  c plan for what to do if cognitive behavioural methods 
do not lift mood within a speciﬁ  ed period (e.g. contact the gen-
eral practitioner about medication, contact the therapist for tele-phone discussion or booster sessions, contact emergency services or telephone helplines in the event of serious suicidal thoughts). Recontacting therapists is often difﬁ  cult, as patients may feel that 
they have failed or them down. Therapists should make it clear 
that they consider it a sign of courage to ask for further help, not a sign of weakness.
(e) Training
Cognitive behaviour therapy for depression is a sophisticated treat-

ment, requiring theoretical knowledge, research familiarity, and clinical expertise. The latter is best developed through practical training and close supervision. Core skills have been operational-ized in measures of therapist competency, such as the Cognitive 
Therapy Scale ,
(34) which allow practitioners to judge for themselves 
whether they are indeed practising cognitive behaviour therapy and to monitor skills development.
Treating depressed patients with cognitive behaviour therapy is a 
challenge, especially with severe, chronic, and relapsing depressions 6.3.2.3 cognitive behaviour therapy for depressive disorders

SECTION 6  treatment methods in psychiatry 1312
and depression comorbid with other conditions. Therapist compe-
tency (the ability to carry out the treatment as intended and to an adequate standard) has a direct impact on outcome. Thus the need for experienced therapists, and for adequate training and ongoing supervision, especially with more difﬁ  cult groups, cannot be over-
emphasized.
(10,11)
Where established training institutes exist, it is wise to take 
advantage of their expertise. Even where no local institute is available, expert therapists from established centres often travel internationally to deliver conferences, workshops, seminars, and supervision—notably the triennial World Congress of Cognitive and Behaviour Therapies.
However, novice therapists will sometimes have little option but 
to supervise themselves, using clinical texts as a knowledge base. Therapists at all skill levels will beneﬁ  t from regularly monitoring

to supervise themselves, using clinical texts as a knowledge base. Therapists at all skill levels will beneﬁ  t from regularly monitoring 
audio or video recordings of their treatment sessions, using the Cognitive Therapy Scale  to identify strengths and areas in need 
of improvement. Even if no more experienced practitioner is available, peer supervision with interested colleagues is helpful. It provides external feedback on clinical practice, and makes other 
forms of learning possible (role play, study groups, etc.).
(f) Self-care
Depression is an infectious disease. It is easy for psychological

Depression is an infectious disease. It is easy for psychological 
therapists (especially if relatively inexperienced) to become con-taminated by patients’ hopelessness. Therefore supervision should include a focus on the therapist’s own thoughts and feelings. Therapists with a substantial proportion of depressed clients should also ensure that they leaven their day by planning life-enhancing and pleasurable experiences, and should be prepared to use cognitive behavioural methods to address their own negative thoughts.

The Beck Institute for Cognitive Therapy and Research in Philadelphia, Pennsylvania, runs extramural courses and training programmes (www.beckinstitute.org), as does the Oxford Cognitive Therapy Centre (www.octc.co.uk), who also offer a selection of CBT oriented booklets for patients and clinicians. The Academy of Cognitive Therapy offers information about CBT, training in CBT, certiﬁ  cation as a cognitive therapist, and (once a member) access to 
a ListServe on which issues relating to theory, research, and clinical practice can be discussed with experienced cognitive therapists (www.academyofcognitivetherapy.org) The International Associa-tion of Cognitive Psychotherapy (www.cognitivetherapyassociation.org) also has a ListServe and hosts regular conferences in member countries. Different countries also have their own national organi-zations promoting CBT, for example, the American Association 
for Behavioural and Cognitive Therapies (www.aabt.org), the

for Behavioural and Cognitive Therapies (www.aabt.org), the 
Australian Association for Cognitive and Behavioural Therapies (www.aabct.org), and the British Association for Behavioural and Cognitive Psychotherapies (www.babcp.com). These will be able to offer information about training opportunities.
A number of texts describe the theory and practice of CBT for depression 
in some detail.(1,17,21) Practical ideas can also be found in self-help texts 
for patients.For the clinician:
Beck, J.S. (1995). Cognitive therapy: basics and beyond . Guilford Press, 
New Y ork.
Fennell, M.J.V . (1989). Depression. In Cognitive behaviour therapy for 
psychiatric problems: a practical guide  (eds. K. Hawton, P .M. Salkovskis, 
J. Kirk, and D.M. Clark). Oxford Medical Publications, Oxford.
Fennell, M. J. V ., Westbrook, D., and Benneth-Levy, J. (2004). Depression. 
In The Oxford guide to behavioural experiments in cognitive therapy

(eds. J. Benneth-Levy, G. Butler, M.J.V . Fennell, et al. ). Oxford 
For the patient:
Beck, A.T. and Greenberg, R.L. (1974). Coping with depression . Available 
from The Beck Institute of CBT and Research, GSB Building, City Line and Belmont Avenues, Suite 700, Bala Cynwyd, Philadelphia, PA 19004–1610, USA.
Burns, D.D. (1980). Feeling good . New American Library, New Y ork.
Butler, G. and Hope, A. (2007). Manage your mind  (2nd edn). Oxford 
Fennell, M.J.V . (1999). Overcoming low self-esteem . Constable Robinson, 
London.
Gilbert, P . (1996). Overcoming depression . Constable Robinson, London.
Greenberger, D. and Padesky, C.A. (1995). Mind over mood , Chap. 10. 
Westbrook, D. (1999). Coping with depression . Available from: Oxford

Westbrook, D. (1999). Coping with depression . Available from: Oxford 
Cognitive Therapy Centre, Dept of Clinical Psychology, Warneford Hospital, Oxford OX3 7JX, UK.
Subjective experience:
Solomon, A. (2002). The noonday demon . Simon & Schuster, New Y ork.
Styron, W. (1991). Darkness visible . Jonathan Cape, London.
Wolpert, L. (1999). Malignant sadness . Faber, London.
Current research and theoretical developments are best followed through 
professional journals (primarily psychiatry and clinical psychology—see the reference list for examples), available in libraries and through the Internet.
1. Beck, A.T., Rush, A.J., Shaw, B.F., et al.  (1979). Cognitive therapy of 
2. Beck, A.T. (1963). Thinking and depression: 1. Idiosyncratic content and 
cognitive distortions. Archives of General Psychiatry ,9, 324–33.

3. Beck, A.T. (1964). Thinking and depression: 2. Theory and therapy. 
Archives of General Psychiatry ,10, 561–71.
4. Beck, A.T. (1967). Depression: clinical, experimental and theoretical 
5. Rush, A.J., Beck, A.T., Kovacs, M., et al.  (1977). Comparative efﬁ  cacy of 
cognitive therapy and pharmacotherapy in the treatment of depressed outpatients. Cognitive Therapy and Research ,1, 17–37.
6. Hollon, S.D., Thase, M.E., and Markowitz, J.C. (2002). Treatment & 
prevention of depression. Psychological Science in the Public Interest ,
3, 39–77.
7. Paykel, E.S., Scott, J., Cornwall, P .L., et al. (2005). Duration of relapse 
prevention after cognitive therapy in residual depression: follow-up of controlled trial. Psychological Medicine ,35, 59–68.

8. Jarrett, R.B., Kraft, D., Doyle, J., et al. (2001). Preventing recurrent 
depression using cognitive therapy with and without a continuation phase. Archives of General Psychiatry ,58, 381–8.
9. Vos, T., Corry, J., Haby, M.M., et al.  (2005). Cost-effectiveness of 
cognitive-behavioural therapy and drug interventions for major depression. The Australian and New Zealand Journal of Psychiatry ,
39, 683–92.

1313
10. DeRubeis, R.J., Hollon, S.D., Amsterdam, J.D., et al. (2005). Cognitive 
therapy vs. medications in the treatment of moderate to severe 
depression. Archives of General Psychiatry ,62, 409–16.
11. Hollon, S.D., DeRubeis, R.J., Shelton, R.C., et al. (2005). Prevention 
of relapse following cognitive therapy vs. medications in moderate to severe depression. Archives of General Psychiatry ,62, 417–22.
12. Ingram, R.E. (2003). Origins of cognitive vulnerability to depression. 
Cognitive Therapy & Research ,27, 77–88.
13. McGinn, L.K., Cukor, D., and Sanderson, W. (2005). The relationship 
between parenting style, cognitive style and anxiety and depression: 
does increased early adversity inﬂ  uence symptom severity through the 
mediating role of cognitive style? Cognitive Therapy & Research ,
29, 219–42.
14. Alloy, L.B., Abramson, L.Y., Whitehouse, W.G., et al.  (2006). Prospective 
incidence of ﬁ  rst onsets and recurrences of depression in individuals

incidence of ﬁ  rst onsets and recurrences of depression in individuals 
at high and low cognitive risk for depression. Journal of Abnormal 
Psychology , 115, 145–56.
15. Segal, Z.V ., Gemar, M., and Williams, S. (1999). Differential cognitive 
response to a mood challenge following successful cognitive therapy or pharmacotherapy for unipolar depression. Journal of Abnormal 
Psychology ,108, 3–10.
16. Lau, M.A., Segal, Z.V ., and Williams, J.M.G. (2004). T easdale’s 
differential activation hypothesis: implications for mechanisms of 
depressive relapse and suicidal behaviour. Behaviour Research and 
Therapy ,42, 1001–17.
17. Fennell, M.J.V ., Westbrook, D., and Bennett-Levy, J. (2004). Depression. 
In The Oxford guide to behavioural experiments in cognitive therapy  (eds. 
J. Bennett-Levy, G. Butler, M.J.V . Fennell, et al. ). Oxford University 

18. Tang, T.Z., DeRubeis, R.J., Beberman, R., et al.  (2005). Cognitive 
changes, critical sessions, and sudden gains in cognitive-behavioural therapy for depression. Journal of Consulting and Clinical Psychology ,
73, 168–72.
19. Dimidjian, S., Hollon, S.D., Dobson, K.S., et al. (2006). Randomized 
trial of behavioural activation, cognitive therapy, and antidepressant 
medication in the acute treatment of adults with major depression. Journal of Consulting and Clinical Psychology ,74, 658–70.
20. Scott, J., Payken, E., Morris, R., et al. (2006). Cognitive behavioural 
therapy for severe and recurrent bipolar disorders. Randomised controlled trial. The British Journal of Psychiatry ,188, 313–20.
21. Moore, R.G. and Garland, A. (2003). Cognitive therapy for chronic and 
persistent depression . Wiley, Chichester, UK.

22. American Psychiatric Association. (1994). Diagnostic and statistical 
23. Beck, A.T., Ward, C.H., Mendelson, M., et al.  (1961). An inventory for 
measuring depression. 
Archives of General Psychiatry ,4, 561–71.
24. Beck, A.T., Weissman, A., Lester, D., et al.  (1974). The measurement of 
pessimism: the Hopelessness Scale. Journal of Consulting and Clinical 
Psychology ,42, 861–5.
25. Beck, A.T. (1993). Beck scale for suicide ideation  (manual ). Psychological 
Corporation, San Antonio.
26. Persons, J.B. (1989). Cognitive therapy in practice: a case formulation 
approach . Norton, New Y ork.
27. Beck, A.T. and Greenberg, R.L. (1974). Coping with depression .

Available from The Beck Institute of Cognitive Therapy and Research, GSB Building, City Line and Belmont Avenues, Suite 700, Bala Cynwyd, Philadelphia, PA 19004–1610, USA.
28. Papageorgiou, C. and Wells, A. (2003). Depressive rumination: nature, 
theory and treatment . Wiley, Chichester.
29. Segal, Z.V ., Williams, J.M.G., and T easdale, J.D. (2002). Mindfulness-
based cognitive therapy for depression: a new approach to preventing relapse . Guilford, New Y ork.
30. T easdale, J.D., Segal, Z.V ., Williams, J.M.G., et al.  (2000). Reducing risk 
of recurrence of major depression using Mindfulness-Based Cognitive Therapy. Journal of Consulting and Clinical Psychology ,
68, 615–23.
31. Ma, J. and T easdale, J.D. (2004). Mindfulness-based cognitive therapy

31. Ma, J. and T easdale, J.D. (2004). Mindfulness-based cognitive therapy 
for depression: replication and exploration of differential relapse prevention effects. Journal of Consulting and Clinical Psychology ,
72, 31–40.
32. Padesky, C.A. (1994). Schema change processes in cognitive therapy. 
Clinical Psychology and Psychotherapy ,1, 267–78.
33. Beck, A.T., Freeman, A., Davis, D.D., et al. (2004). Cognitive therapy of 
personality disorders . Guilford Press, New Y ork.
34. Y oung, J.E. and Beck, A.T. (1980). Development of an instrument 
for rating cognitive therapy: the cognitive therapy scale . University of 
Pennsylvania, Philadelphia, PA.
6.3.2.4 Cognitive behaviour 
therapy for schizophrenia
Cognitive behaviour therapy ( CBT ) for schizophrenia focuses on

Cognitive behaviour therapy ( CBT ) for schizophrenia focuses on 
the core psychotic symptoms of hallucinations and delusions. Other psychosocial approaches to psychosis (e.g. intervention with families and to promote medication compliance) also frequently use CBT techniques. In this chapter, however, we focus on CBT for delusional beliefs and other psychotic phenomena and review evidence for its efﬁ  cacy.
Background: assumptions and 
common components
The CBT approach to psychotic symptoms comprises two different 
strands each with their own theoretical basis, although of late these two approaches have become conjoined in practice.
Coping strategy enhancement
The ﬁ  rst approach is inspired by the stress-vulnerability model of

The ﬁ  rst approach is inspired by the stress-vulnerability model of 
schizophrenia. Vulnerability here is viewed as a ‘black box’ , drawing mainly on the biomedical tradition. It is assumed that stressors capable of triggering or exacerbating symptoms may be generated or modulated by the individual. For example, stressors emanating from the social environment are modulated by the patient’s own appraisal of their stressfulness and his or her coping strategies.
Another class of stressors consists of the symptoms themselves.

Another class of stressors consists of the symptoms themselves. 
It is assumed that certain strategies used to cope with symptoms are unhelpful and generate stress in the individual, in turn, exacer-bating symptoms. These strategies are conventionally divided into affective strategies (e.g. relaxation, sleep, etc.), behavioural strate-gies (being active, drinking alcohol, etc.), and cognitive strategies (distraction, challenging voices, switching attention away from voices, etc.). This underpins the approach known as Coping 
Strategy Enhancement
(1) whereby patients are offered a range of 
strategies which are implemented in an empirical fashion to deter-mine their effectiveness in symptom control. For example, Falloon and Talbot
(2) documenting the coping strategies used by voice-
hearers, concluded that those who had multiple strategies available 6.3.2.4 cognitive behaviour therapy for schizophrenia

SECTION 6  treatment methods in psychiatry 1314
to them were more able to cope with their voices. Tarrier(3) on the 
other hand, focusing on a wider range of psychotic symptoms, concluded that those who applied strategies consistently tended to fare the best. This approach views the individual as an active agent who attempts to reduce the threat or distress posed by psychotic symptoms, but does not concern itself with the content or meaning that psychotic symptoms may have to the individual. There is also, in this approach, assumed to be a fundamental discontinuity between normal and abnormal functioning that comes about once the biological vulnerability is ‘online’ .
CBT for delusions and hallucinations
The second CBT strand draws its theoretical strength from the cog-nitive therapy approach.
(4) Early work in this area focused on the

(4) Early work in this area focused on the 
similarity between normal (but strongly held) beliefs and delusions, in terms of the psychological processes at play in their maintenance. For example, Brett-Jones et al.
(5) showed that delusions, like every-
day beliefs, lead the individual to recruit evidence to support them and to de-emphasize or dismiss contradictory evidence. Continuing the exploration of the continuity between normal and delusional beliefs, Birchwood and Chadwick
(6) argued that certain beliefs

(6) argued that certain beliefs 
about voices’ power may be considered as a quasi-rational response to anomalous experience, with the meaning attributed to them in terms of identity, power, and the consequence of disobedience determining distress and behaviour in relation to the voice. Other work has drawn on the cognitive therapy approach in depression, which emphasizes the importance of evaluative beliefs about the self (e.g. self-worth) in the genesis and maintenance of depressed mood.
(7) The application of this to psychosis also emphasizes 
evaluative beliefs about the self. The precise relationship between self-evaluative beliefs and delusional thinking is a much debated issue of the present time. It has been argued, for example, that delu-sions may serve the function of defending the individual from the full impact of low self-worth through blaming others for negative events rather than the self. This is the so-called ‘paranoid defence’ .
(8)

(8)
The content of psychotic thinking often reﬂ  ects such personal 
issues. For example, for the patient who has been sexually abused, this theme tends to crop up in the content of voice activity or in the supposed identity of the voice.
(6)
This early work has been elegantly drawn together in a cognitive 
model of psychosis by Phillipa Garety and her colleagues. In a sem inal 
paper(9) they propose a model of the cognitive processes leading to 
the positive symptoms of psychosis. In brief, positive symptoms in psychosis are hypothesized to begin with basic cognitive distur-bances with lead to ambiguous sensory input, the intrusion into consciousness of unintended material from memory, or to difﬁ  cul-
ties with the self-monitoring of intentions and actions, such that they are experienced as alien. This result in anomalous conscious experiences such as actions being experienced as unintended, rac-ing thoughts, thoughts appearing to be broadcast, and thoughts experienced as voices.

However, the authors argue that such anomalous experiences 
alone do not develop into full-blown psychotic experiences unless an individual appraises them as externally caused and personally signiﬁ  cant. Such appraisals are the results of particular reasoning 
processes (e.g. data gathering bias or externalizing attributional 
style), dysfunctional personal schemas (e.g. low self-esteem born of 
adverse social experience), emotional states (e.g. anxiety and depression), and appraisal of the experience of illness.This model integrates the two strands of cognitive therapy.

adverse social experience), emotional states (e.g. anxiety and depression), and appraisal of the experience of illness.This model integrates the two strands of cognitive therapy. 
It suggests, for example, that the reduction in dysfunctional emo-tional states through, for example, coping strategy enhancement, will contribute to alterations in the attributions, which are impor-tant in the formation and maintenance of the positive symptoms. Similarly, it provides a theoretical basis for the basic techniques traditionally used in the second strand of CBT. Such techniques encourage the individual to weigh evidence that contradicts a delusion as a strategy to compensate for the basic information-processing abnormality, challenge negative self-schemata, and combat depression.
Evaluation

In recent years the volume of trials evaluating CBT for psychosis has greatly expanded, with approximately 20 such studies now reported. Most of these have been conducted in the United Kingdom among patients with chronic schizophrenia. The strength of the data is now sufﬁ cient for The UK National Institute for Clinical excellence to 
state that cognitive behavioural therapy should be available as a treatment option for people with schizophrenia.
(10)
An up-to-date review(11) reporting the analysis of 19 studies of

(10)
An up-to-date review(11) reporting the analysis of 19 studies of 
CBT for positive symptoms in schizophrenia, found a mean effect size of 0.37. The authors concluded that 74 per cent of these studies achieved small effect sizes, 32 per cent moderate effect sizes, and 16 per cent large effect sizes in improving positive psychotic symptoms, relative to standard psychiatric care. Furthermore, they argued that this is unlikely to be due to publication bias. The effect sizes for CBT versus standard treatment among patients with chronic illness were greater than those among acutely ill patients. This may have been due to a ceiling effect caused by the effective-ness of medication in reducing symptoms in ﬂ  oridly ill inpatients.

Similarly, the better the design of the trial, the smaller the treat-ment effect size, suggesting that CBT is not the panacea for all psychotic ills that it may have originally appeared.
With regard to relapse prevention, CBT appears to be more 
successful when the intervention is focused on relapse prevention, rather than relapse prevention being one of a series of compone nts.
(11)
For example, Gumley and his colleagues(12) were able to demonstrate 
that a group of patients with psychosis receiving targeted CBT for relapse prevention had almost half the rate of relapse over a 12-monthperiod compared with a similar group receiving treatment as usual (18.1 versus 34.7 per cent). In this study, the CBT treatment con-sisted of an engagement phase, early signs of relapse monitoring with a personalized questionnaire, and targeted CBT at the ﬁ  rst 
sign of impending relapse.
While large, pragmatic trials of CBT treatment packages have

While large, pragmatic trials of CBT treatment packages have 
yielded the above favourable results, investigating the active elements of the interventions is difﬁ  cult because CBT for psychosis 
now refers to a wide range of treatments.
Furthermore, although the conceptual basis of CBT emphasizes 
the link between emotion, cognition, and behaviour, modifying 
emotion in psychosis has been relatively neglected in CBT trials, in favour of outcomes based on modiﬁ  cation of delusions and hallu-
cinations themselves.
It has been proposed that CBT should be focused into more tar-
geted interventions aimed at emotional dysfunction or distress and/or behavioural anomaly in psychosis that is directly or indi-rectly linked to psychosis symptoms.
(13) This approach recognizes

1315
that while changing the psychosis symptoms might not always be 
possible, it may well be feasible to change the affective consequences of the symptoms or the diagnosis. This affective change may have further beneﬁ  ts in reducing the severity of the psychosis experience 
per se .
For example:
1 CBT can be used to reduce distress, depression, and problem 
behaviour associated with commanding voices, without chang-ing the frequency or content of the voices themselves.
(14)
2 CBT can focus on anxiety, depression, and interpersonal difﬁ  -
culty in individuals at high risk of developing psychosis.(15)
3 CBT can focus on the relapse prodrome to prevent relapse in 
psychosis.(12)
4 CBT can focus on ‘comorbid’ depression and social anxiety, 
including the patient’s appraisal of the diagnosis and its stigma-tizing consequences.
(16)
5 CBT can be used to reduce stress reactivity, thereby increasing 
resilience to life stress and preventing psychotic relapse.(17)

(16)
6 CBT can be used to increase self-esteem and social conﬁ  dence in 
people with psychosis.(18)
Coping strategy enhancement involves developing a coping repertoire and over-rehearsing it to facilitate an automatic coping response.
(19) It can either be used to improve an individual’s 
attempts to cope with his or her voices by developing an under-standing of factors that trigger or improve the voices, or to test the reality of thoughts about the voices.
For example, therapy with a patient who hears threatening 
and frightening voices exacerbated of being alone might involve: An explicit congratulation on the strength involved in withstand-ing the voices’ incessant activity; strengthening of coping strategies involving seeking company and social support; and the use of a personal stereo for distraction.

Cognitive therapy to challenge delusions and 
dysfunctional assumptions
The application of cognitive therapy in challenging of delusions 
and dysfunctional beliefs draws upon the approach described by Chadwick et al .
(20) and builds upon the pioneering work of 
Chadwick and Lowe.(21)
Engaging patients is perhaps the greatest challenge facing a ther-
apist. It is noticeable that many individuals either never attend or do so for a few sessions and then stop. Once individuals get past the opening strategies of cognitive therapy they usually see therapy through. Careful attention to appropriate therapeutic technique can maximize client engagement. Similarly, Kuipers et al.
(22) report 
that a response to CBT in their study was associated with greater cognitive ﬂ  exibility concerning delusions at baseline. This suggests 
that the sufferer may need some small degree of insight into the fact that he might be mistaken, to beneﬁ  t from cognitive therapy 
for delusions.

The process involves six basic steps as summarized in 
Table 6.3.2.4.1.(a) Viewing delusions as beliefs, not facts
The ﬁ  rst technical difﬁ  culty to be encountered is the necessary 
move to aid the client in conceptualizing a delusion as a belief and not a fact. This move is an essential part of CBT for all emotional problems, but is difﬁ  cult at the best of times. With depression, for 
example, patients often struggle to appreciate that their sense of worthlessness, which is so concrete to them, is actually a belief they hold and is different from a knowledge of events and facts. With delusions there is the added complication that the therapist might be perceived as being just another person who disbelieves the patient.
There are two central points to bear in mind when seeking to

There are two central points to bear in mind when seeking to 
reconceptualize delusions as beliefs, not facts—why it is being done and how it is done.
(20)
The purpose of clarifying that delusions are beliefs, not facts, is 
to empower the patient and offer a way of easing his or her distress. If the patient really is being persecuted by a powerful organization, or has a radio transmitter and receiver in his head, neither he nor the therapist can actually change this. The patient feels that he knows this as a fact, with the consequence that he feels frustrated and helpless as well as distressed. However, if the patient only believes this to be true, then he gains the freedom to examine his beliefs and perhaps change his distressing feelings and behaviour and experiences himself. In this sense it is in his best interest for the delusion to be false.
How this process takes place is critical. The process of Socratic

How this process takes place is critical. The process of Socratic 
questioning is not one of persuading a patient that he is wrong and that you, the therapist, are right. This mistake is made all too often. Rather, in Socratic dialogue the therapist helps the patient to draw 
on his own doubt and experience in order to realize that there are 
other ways in which he is able to make sense of his experience. So, when the therapist pursues the conceptual step of clarifying that a delusion is only a belief, the patient’s own doubt, past or present, his own contradictory experience and behaviour, and concern about the possibility that the delusion is wrong are accessed. Many patients have ‘double awareness’ of delusions—on the one hand they believe them ﬁ  rmly and are distressed and disturbed by them,

yet on the other hand they behave in ways that contradict the delu-sion, and they believe that working with a therapist might ease the problem. Finally, the therapist must accept that it is acceptable if the patient does not alter his belief. The process is ‘collaborative empiricism, not indoctrination’ .
(17)
(b) Developing a rationale for questioning the delusion
Patients are usually used to being told by family and carers that their beliefs are wrong, that they are deluded. It is easy for a therapist to Table 6.3.2.4.1 A summary of the steps in cognitive therapy for 
delusions
1 Viewing delusions as beliefs, not facts
2 Developing a rationale for questioning the delusion
3 Weakening delusions4 Utilizing inconsistency and irrationality5  Reformulating delusions as reactions to, and attempts to make sense of, 
speciﬁ  c experience
6 Assessing the delusion and alternative, and empirical testing6.3.2.4 cognitive behaviour therapy for schizophrenia

SECTION 6  treatment methods in psychiatry 1316
prepare the intervention well and embark on it before the patient is 
clear of the purpose and possible beneﬁ  t, thus causing early loss of

engagement. It is revealing to turn the engagement question on its head and to consider why a patient should ever wish to engage in therapy. With emotional problems patients identify their problems as depression, anger, anxiety, guilt, etc.; with delusions and halluci-nations this is not so—patients predominantly present problems which they believe are actual events (persecution, voices, passivity). This means that they have no clear objective and therefore have no particular motivation to engage. The key reason for a patient to reconsider delusional beliefs is that it will help him feel less distress and it will free him to behave differently and to pursue the things he wants more directly. What the therapist does gradually through the unfolding cognitive assessment is to clarify with the patient that he is experiencing emotional and behavioural problems, and that these are tied to his beliefs (delusional and evaluative). The thera-pist then needs to explore with the patient how the

patient that he is experiencing emotional and behavioural problems, and that these are tied to his beliefs (delusional and evaluative). The thera-pist then needs to explore with the patient how the delusion affects his life and how his life would be different (i.e. better or worse) if the delusion were false.

(20) In this way, the therapist slowly encour-
ages the patient to view the delusion not as an important discovery but as a belief that results in distress (e.g. fear, anxiety) and causes him to behave in ways which he would rather not (e.g. avoid things he would otherwise like to do).
(c) Weakening delusions
Disputing comprises four elements:(20)
◆ The evidence for the belief is challenged, in inverse order of its 
importance to the delusion.
◆ The internal consistency and plausibility of the delusional 
system is questioned.
◆ Following Maher,(23) the delusion is reformulated as being an 
understandable response to, and way of making sense of, speciﬁ  c 
experience, and a personally meaningful alternative is then constructed.
◆ The individual’s delusion and the alternative are assessed in the 
light of the available information.
◆ Challenging the evidence for the belief.
Watts et al.(24) argued that a danger when trying to modify delu-

sions, indeed, all strongly held beliefs, was psychological reactance, whereby too direct an approach served only to reinforce the belief. They offered two principles to minimize this possibility: begin with the least important belief, and also work with the evidence for the belief rather than the belief itself.
Accordingly a ‘verbal challenge’ of delusions begins by question-
ing the evidence for the belief, and this process begins with the least signiﬁ  cant item of evidence and works up to the most signiﬁ  cant

ing the evidence for the belief, and this process begins with the least signiﬁ  cant item of evidence and works up to the most signiﬁ  cant 
one. Our preferred approach is that with each item of evidence the therapist questions the patient’s delusional interpretation and puts forward a more reasonable and probable one. The customary approach in CBT is for the patient to be asked to generate the alter-native interpretation(s), rather than the therapist supply one, but we have found that for certain patients this conventional tactic is a 
weak intervention.
When the therapist questions the evidence for a delusion there 
are two distinct but related objectives. One is to encourage the patient to question and perhaps even to reject the evidence for his or her belief, and in this way perhaps to undermine the patient’s

are two distinct but related objectives. One is to encourage the patient to question and perhaps even to reject the evidence for his or her belief, and in this way perhaps to undermine the patient’s 
conviction in the delusion itself. For some individuals challenging the evidence is a very powerful intervention and one that produces a substantial reduction in delusional conviction. However, more commonly this does not happen, but challenging evidence is still valuable in that it does impart insight into the connection between events, beliefs, affect, and behaviour. This is the second objective of challenging evidence, namely to convey the essentials of the ABC approach, i.e. that strongly held beliefs inﬂ  uence affect,

behaviour, and cognition (i.e. interpretation) for all people. Core beliefs recruit or bias everyday inferences and automatic thoughts. However, this means that people often impose an interpretation on to events, which is unwarranted, and because we are prone towards selectively processing information that confirms our beliefs, this goes undetected. In other words, it is understandable that a patient should interpret a particular event in line with his delusion because this is merely one occurrence of a general ten-dency, and conﬁ  rmation bias, common to all of us. In therapy, it is 
helpful to convey the ordinariness and normality of this process with everyday examples.
Having considered the alternatives, the patient is then asked to

Having considered the alternatives, the patient is then asked to 
rate his conviction about each; regardless of how convinced he remains that the delusional interpretation is correct, it is usual to move on to the next piece of evidence. The therapist does not have to change what the patient thinks, but only to offer a fresh insight into the way he is thinking.
(d) Utilizing inconsistency and irrationality
Although delusions contain differing degrees of inconsistency and irrationality, they all seem to contain some. For example, Margaret believed that she could not act or make a decision with-out reference to her voice; however, she described periods when she was relaxed and the voices quiescent where she would be making decisions. Such inconsistencies can be therapeutically useful.
(e)  Reformulating delusions as reactions to, and attempts to 
make sense of, speciﬁ  c experience

We always construe a delusion as both a reaction to and an attempt 
to make sense of certain puzzling and often threatening experience. It is an understandable and reasonable attempt to ﬁ  nd meaning at 
a time when the individual is bewildered, anxious, and frightened. But, the delusion carries a cost in terms of distress and disturbance, which the individual might not otherwise experience. This is how delusions may be explained to patients.
(23)
At this stage the therapist has commenced the process of challen-
ging the delusional belief, re-formed the delusion as an attempt to make sense of certain experiences (e.g. primary symptoms, trau-ma) and raised the idea that the delusion is psychologically func-tional (i.e. it eases puzzlement) and perhaps linked to evaluative beliefs.
(f)  Assessing the delusion and alternative, and 
empirical testing

Finally, the patient and therapist need to assess the delusion and 
alternative in the light of the available evidence and previous discussion. The therapist may spell out the advantages of the alter-native interpretative framework, which can also be discussed by 
relating it to the patient’s experiences.

1317
It is an integral part of CBT that the belief or assumption under 
consideration be tested empirically. Such reality testing involves planning and performing an activity that validates or invalidates a belief, or part of a belief.
When working with delusions, we set up a clear alternative belief 
in opposition to the delusion, clarifying with the patient in advance precisely what has to happen for each to be supported and refuted. For example,
(20) Alison believed that by repeating her voice’s 
command (e.g. ‘The price of milk will rise a billion times’) it would 
actually happen by transmitting the thought to a member of the government who would act upon it. The empirical test involved repeating the voice and purchasing milk before and after doing so, predicting that within 2 weeks the price of milk would at least double. If it did not, the alternative (that the power to change events was very weak) would be strengthened.
Cognitive therapy for beliefs about auditory

Cognitive therapy for beliefs about auditory 
The above techniques can be applied to challenge beliefs about 
‘voices’ using the following three steps:
Assessing the personal meaning a voice has for a person is the deﬁ ning feature of the cognitive approach to assessing auditory 
hallucinations. The delusional beliefs found to be most signiﬁ  cant 
are those relating to a voice’s identity, purpose, power, knowledge, and the consequences of compliance and resistance. The semi-structured interview schedule developed by Chadwick and Birchwood
(6, 25) is recommended.
(b) Disputing beliefs about voices

The thrust of the therapist’s challenge is that the beliefs are reason-able and understandable reactions to, and attempts to make sense of, the auditory hallucinations. The therapist reviews evidence and inconsistency, and plans tests, with the aim always of evaluating two possible meanings: that the beliefs are true, a discovery, or that they are reasonable and understandable, but mistaken. As ever, it is vital that the therapist really practises Socratic questioning and works collaboratively. This involves drawing out patients’ own doubts, puzzlement, double awareness, critical faculty, etc., rather than forcing a contradiction on them.
The major piece of evidence for the delusional beliefs is always 
the actual voices, especially their content—these are, after all, the activating events that the delusions are invoked to explain. The role of beliefs is critical because individuals usually attribute voices

with a power and knowledge that goes well beyond what they have 
actually said. Several examples of challenging follow.
It is really quite common for beliefs about compliance (e.g. ‘If I 
don’t do what my voice says I will be punished’) not to ﬁ  t patients’ 
experiences, and perhaps it is only their emotional impact which prevents patients from abandoning them. Kate, for example, believes ‘If I drop my guard the voices will kill me’ , but in fact she has dropped her guard on many occasions without consequence. This might be pointed out as follows. ‘Kate, you say that the voices have the power to kill you and you must be on your guard constantly. I certainly appreciate the fear that this must create. What puzzles me though is that your guard is often down, like when you are asleep. How is it that they have not succeeded in all these years?’The appearance of being all knowing (omniscience) is a vital 
aspect of many voices
(22) and often features as a key piece of evi-

dence that the identity of the voice is superhuman. It leaves indi-viduals feeling exposed and vulnerable and very prone to guilt and shame. Alice believes that her voice is a prophet endowed with the ability to foretell the future. In particular, the voice anticipates exactly the arrival of her husband home from work each day. T o begin the process of questioning she was asked: ‘Let’s suppose for a moment that the voice cannot foretell the future; can you think of any other possible explanations for last night’s prediction?’ One such possibility was that the voice was making a very safe guess.
(c) Testing beliefs about control

A useful strategy is to use a procedure whereby the patient and therapist learn to engineer situations to start or increase the prob-ability of hearing voices, and then to stop or reduce them. In this way the patient gains a surprising degree of control over the voice. The initial assessment provides information about cues that pro-voke voices for a particular individual; concurrent verbalization is known to stop or diminish voices temporarily. This information is combined in the following ﬁ  ve steps.
◆ Identify cues that increase and decrease voices.
◆ Practise the use of ‘increasing’ and ‘decreasing’ strategies within a 
session.
◆ Propose the notion that ‘control’ requires the demonstration that 
voice activity can be turned up/on or down/off.
◆ In sessions encourage the patient to initiate or increase voice 
activity for short periods then reduce or stop it.
◆ Elicit changes in the patient’s belief about his control over 
the voices.

The above process has been applied in a targeted way to the special 
case of beliefs about command hallucinations. These are high-risk, distressing, and relatively common symptoms of schizophrenia.
For example, Byrne and her colleagues
(26) have developed a spe-
ciﬁ c cognitive therapy for command hallucinations, which draws 
on the above techniques. Using the methods of collaborative empiricism and Socratic dialogue, the therapist seeks to engage the client to question, challenge, and undermine the power beliefs, then to use behavioural tests to help the client gain disconﬁ  rming 
evidence against the beliefs. These strategies are also used to build clients’ alternative beliefs in their own power and status, and ﬁ  nally,

evidence against the beliefs. These strategies are also used to build clients’ alternative beliefs in their own power and status, and ﬁ  nally, 
where appropriate, to explore the origins of the schema so clients have an explanation for why they developed those beliefs about the voice in the ﬁ  rst place. They were able to show that this process 
produce significant reductions in compliance behaviours and favourable changes in beliefs about the power, superiority and need to comply with the voices, despite the frequency, loudness, and content of the voices staying the same.
(14)
CBT for psychosis is a rapidly developing ﬁ  eld, and one that has 
borne considerable fruit in terms of providing effective treatments and a basis upon which a dialogue between the patient and the professional can take place about matters of great concern and a source of much distress.6.3.2.4 cognitive behaviour therapy for schizophrenia

SECTION 6  treatment methods in psychiatry 1318
Nelson, H. (2005). Cognitive behavioural therapy with delusions and 
hallucinations: a practice manual  (2nd edn). Nelson Thornes, 
Cheltenham.
Morrison, A.P . (2002). A casebook of cognitive therapy for psychosis . Brunner/
Byrne, S., Meaden, A., Trower, P ., et al. (2006). A casebook of cognitive 
behaviour therapy for command hallucinations: a social rank theory .
 1. Tarrier, N., Yusupoff, L., Kinney, C., et al. (1998). Randomised 
controlled trial of intensive cognitive behavioural therapy for patients with chronic schizophrenia. British Medical Journal ,317, 303–7.
 2. Falloon, I.R.H. and Talbot, R. (1981). Persistent auditory 
hallucinations: coping mechanisms and implications for management. 
Psychological Medicine ,11, 329–39.
 3. Tarrier, N. (1987). An investigation of residual positive symptoms in

 3. Tarrier, N. (1987). An investigation of residual positive symptoms in 
discharged schizophrenic patients. British Journal of Clinical Psychology ,
26, 141–3.
 4. Beck, A.T., Rush, A., Shaw, B., et al. (1979). Cognitive therapy of 
depression . Guilford, New Y ork.
 5. Brett-Jones, J., Garety, P ., and Hemsley, D.R. (1987). Measuring 
delusional experiences: a method and its application. British Journal of 
Clinical Psychology ,26, 257–65.
 6. Birchwood, M. and Chadwick, P .D. (1997). The omnipotence of voices. 
II. T esting the validity of the cognitive model. Psychological Medicine ,
27, 1345–53.
 7. Garety, P .A., Kuipers, L., Fowler, D., et al. (1994). Cognitive behavioural 
therapy for drug resistant psychosis. The British Journal of Medical 
Psychology ,67, 259–71.
 8. Bentall, R.P . and Kinderman, P . (1998). Psychological processes and

 8. Bentall, R.P . and Kinderman, P . (1998). Psychological processes and 
delusional beliefs: implications for the treatment of paranoid states. In Outcome and innovation in psychological treatment of schizophrenia
(eds. T. Wykes, N. Tarrier, and S. Lewis), pp. 119–44. Wiley, Chichester.
 9. Garety, P .A., Kuipers, A.E., Fowler, D., et al.  (2001). A cognitive model 
of the positive symptoms of psychosis. Psychological Medicine ,
31, 189–95.
10. National Collaborating Centre for Mental Health. (2003). 
Schizophrenia: full national clinical guideline on core interventions in 
primary and secondary care . Royal College of Psychiatrists and the 
British Psychological Society, London.
11. Tarrier, N. and Wykes, T. (2004). Is there evidence that cognitive 
behavioural therapy is an effective treatment for schizophrenia? A cautious or cautionary tale. Behaviour Research and Therapy ,
42, 1377–401.

12. Gumley, A., O’Grady, M., McNay, L., et al. (2003). Early intervention 
for relapse in schizophrenia: results of a 12-month randomized controlled trial of behavioural therapy. Psychological Medicine ,
33, 419–31.
13 Birchwood, M. and Trower, P . (2006). The future of cognitive 
behavioural therapy for psychosis: not a quasi-neuroleptic. 
British Journal of Psychiatry ,188, 107–8.
14. Trower, P ., Birchwood, M., and Meaden, A. (2004). Cognitive therapy 
for command hallucinations: randomised controlled trial. British Journal of Psychiatry ,184, 312–20.
15. Morrison, A.P ., French, P ., Walford, L., et al. (2004). Cognitive therapy 
for the prevention of psychosis in people at ultra-high risk: randomised controlled trial. British Journal of Psychiatry ,185, 291–7.
16. Iqbal, Z., Birchwood, M., and Chadwick, P . (2000). Cognitive

16. Iqbal, Z., Birchwood, M., and Chadwick, P . (2000). Cognitive 
approach to depression and suicidal thinking in psychosis. 2. T esting the validity of a social ranking model. British Journal of 
Psychiatry ,177, 522–8.17. Myin-Germeys, I., Delespaul, P ., and van Os, J. (2005). Behavioural 
sensitization to daily life stress in psychosis. Psychological Medicine ,
35, 733–41.
18. Hall, P .L. and Tarrier, N. (2003). The cognitive behavioural treatment 
of low self esteem in psychotic patients: a pilot study. Behaviour 
Research Therapy ,41, 317–32.
19. Tarrier, N. (1992). Management and modiﬁ  cation of residual 
psychotic symptoms. In Innovations in the psychological management of 
schizophrenia  (eds. M. Birchwood and N. Tarrier), pp. 38–72. 
20. Chadwick, P .D., Birchwood, M., and Trower, P . (1996). Cognitive 
therapy for delusions, voices and paranoia . Wiley, Chichester.
21. Chadwick, P .D.J. and Lowe, C.F. (1990). Measurement and modiﬁ  cation

21. Chadwick, P .D.J. and Lowe, C.F. (1990). Measurement and modiﬁ  cation 
of delusional beliefs. Journal of Consulting and Clinical Psychology ,
58, 225–32.
22. Kuipers, E., Garety, P ., Fowler, D., et al. (1997). London-East Anglia 
randomised controlled trial of cognitive behavioural therapy for 
psychosis. I. Effects of the treatment phase. The British Journal of 
Psychiatry ,171, 319–27.
23. Maher, B.A. (1988). Anomalous experience and delusional thinking: 
the logic of explanation. In Delusional beliefs  (eds. F. Oltmans and 
B.A. Maher), pp. 5–22. Wiley, New Y ork.
24. Watts, F., Powell, E., and Austin, S.V . (1973). The modiﬁ  cation of 
abnormal beliefs. The British Journal of Medical Psychology ,46, 359–63.
25. Chadwick, D. and Birchwood, M. (1994). The omnipotence of voices. 
A cognitive approach to auditory hallucinations. British Journal of 
Psychiatry ,164, 190–201.

26. Byrne, S., Meaden, A., Trower, P ., et al. (2005). A casebook of cognitive 
behaviour therapy for command hallucinations: a social rank theory approach . Routledge, London.
6.3.3 Interpersonal psychotherapy 
for depression and other disorders
Carlos Blanco, John C. Markowitz, and 
Myrna M. Weissman
Interpersonal psychotherapy (IPT) is a time-limited, diagnosis-
focused therapy. IPT was deﬁ  ned in a manual. Research has estab-
lished its efﬁ  cacy as an acute and chronic treatment for patients 
with major depressive disorder (MDD) of all ages, as an acute treat-ment for bulimia nervosa, and as adjunct maintenance treatment for bipolar disorder.
(1–9) The research ﬁ  ndings have led to its inclu-
sion in treatment guidelines and increasing dissemination into clinical practice.

Demonstration of efﬁ  cacy in research trials for patients with 
major depressive episodes (MDEs) has led to its adaptation and testing for other mood and non-mood disorders. This has included modiﬁ  cation for adolescent and geriatric depressed patients
(10,11)
patients with bipolar(12) and dysthymic disorders;(13,14)  depressed 
HIV-positive(15) and depressed pregnant and postpartum 
patients;(16,17)  depressed primary care patients;(18) and as a mainte-
nance treatment to prevent relapse of the depression.(5) Most of the 
modiﬁ  cations have been relatively minor and have retained the 
general principles and techniques of IPT for major depression.

1319
Non-mood targets have included anorexia, bulimia, substance 
abuse, borderline personality disorder, and several anxiety disorders. In general, outcome studies of IPT have suggested its promise for most psychiatric diagnoses in which it has been studied, with the exceptions of anorexia, dysthymic disorder, and substance use disorders.
(14,19,20)
IPT has two complementary basic premises. First, depression is a 
medical illness, which is treatable and not the patient’s fault. Second, depression does not occur in a vacuum, but rather is inﬂ  u-

enced by and itself affects the patient’s psychosocial environment. Changes in relationships or other life events may precipitate depres-sive episodes; conversely, depressive episodes strain relationships and may lead to negative life events. The goal of treatment is to help the patient solve a crisis in his or her role functioning or social envi-ronment. Achieving this helps the patient to gain a sense of mastery over his or her functioning and relieves depressive symptoms.
Begun as a research intervention, IPT has only lately started to be 
disseminated among clinicians and in residency training pro-grammes. The publication of efﬁ  cacy data, the promulgation of 
practice guidelines that embrace IPT among antidepressant treat-

ments, and economic pressures on length of treatment have led to 
increasing interest in IPT. This chapter describes the concepts and techniques of IPT and its current status of adaptation, efﬁ  cacy data, 
and training. The chapter provides a guide to developments and a reference list, but not a comprehensive review.
IPT traces its theoretical and clinical origins to the interpersonal psychoanalytic theory of Meyer and Sullivan and builds on work of other relational theory including object relations, particularly with regard to attachment. However, it applies this theory within a con-ceptual and clinical framework that differs signiﬁ  cantly from that

of Sullivan and much of relational theory. In contrast with psycho-analytically inspired schools of thought, IPT sees its goals in treat-ing depression and other medical disorders, rather than trying to change overall personality. Pragmatically, IPT opts to narrow its focus to address the area of interpersonal life that seems to require the most immediate attention.
Acknowledging the importance of personality and early 
experience, IPT emphasizes the role of recent stressful events in triggering depression and other psychiatric disorders in vulnerable 
individuals, while it also recognizes the protective role social 
supports play against psychopathology. Nevertheless, IPT is less interested in discerning the cause  of a depressive episode (since it 
assumes the aetiology of depression to be multifactorial) than in using the connection between current life events and the onset of depressive symptoms to help the patient understand and combat the episode of illness.

Compared to other psychotherapies, such as psychoanalytic 
psychotherapy or even cognitive behavioural therapy, IPT is rela-tively young. It is less concerned about maintaining an established orthodoxy than about adapting itself to the needs of the patient. Although IPT theorists have taken into account theoretical devel-
opments in psychiatry and related ﬁ  elds, much of IPT’s evolution 
has been based on the results of clinical trials. As investigations continue into IPT as a treatment for different disorders and popu-lations, further modiﬁ  cation of its theoretical aspects as well as 
techniques are likely.Indications
IPT research has demonstrated its efﬁ  cacy for major depressive disor-
der across a range of patient ages and contexts, and for bulimia ner-vosa. One large trial indicates its efﬁ  cacy (modiﬁ  ed as interpersonal 
social rhythms therapy, or IPSRT) as an adjunctive treatment for bipolar disorder. 
(6) Lesser evidence suggests the potential beneﬁ  ts of

(6) Lesser evidence suggests the potential beneﬁ  ts of 
IPT for several anxiety disorders. (21,22) IPT has shown no advantages 
over control psychotherapies for dysthymic disorder or substance abuse disorders. 
(14,20) For depressed adolescents, IPT has shown not 
only efﬁ  cacy but effectiveness in a school-based programme. (10,11)
Both the physician and patient guides in primary care guidelines

Both the physician and patient guides in primary care guidelines 
for depression list IPT, cognitive behavioural therapy (CBT), behavioural, brief dynamic, and marital therapy as treatments for depression. IPT is spreading from its initial research base in the United States. The IPT manual has been translated into Italian, German, Japanese, Spanish, and French, and is being used ever more widely around the world. Descriptions of IPT have appeared in Spanish, Norwegian, Finnish, and Dutch journals. An International Society for Interpersonal Psychotherapy, established at the American Psychiatric Association Annual meeting in May 2000 in Chicago, has a growing membership and biennial international meetings in 2004 and 2006, and maintains a bibliography of studies.
Because IPT focuses clinically on the social context of the

Because IPT focuses clinically on the social context of the 
depressive episode, researchers have sometimes adapted IPT when applying it to different treatment populations, developing manuals 
for different age groups or subpopulations, and occasionally 
adding focal problem areas. IPT has also been used at different lengths, in different formats, in one pilot couple’s adaptation, and as a telephone intervention. Nonetheless, all these adaptations involve the basic principles that constitute IPT: a no-fault deﬁ  ni-
tion of the patient’s problem as a medical illness, excusing the patient from blame for his or her symptoms; and a continual focus on the relationship between the patient’s moods and life situation. The continuing growth of IPT research precludes an exhaustive description of studies. This chapter presents a selection of key research trials of IPT for mood and other disorders (see Efﬁ cacy )
and offers selected references for further reading.

Although formal contraindications (i.e. situations in which IPT would worsen the patients’ situation) are not known, IPT was never intend-ed to function as a monotherapy for patients with psychotic depres-sion or bipolar disorder. In addition, three controlled trials have found no beneﬁ  t of IPT as a treatment for substance use disorders.
Conducting IPT
Each of the four IPT interpersonal problem areas has discrete goals 
for therapist and patient to pursue. The therapist helps the patient relate life events to mood and other symptoms. In this section we outline the phases of IPT, as well as common strategies and tech-niques used in IPT treatment. We also outline some differences with cognitive behavioural therapy, to which it is often compared.
Phases of treatment
As an acute treatment, IPT has three phases. The ﬁ  rst phase ,

generally covering sessions 1–3, includes diagnostic evaluation, 6.3.3 interpersonal psychotherapy for depression and other disorders

SECTION 6  treatment methods in psychiatry 1320
psychiatric history, and setting the treatment framework. The ther-
apist reviews symptoms, diagnoses the patient as depressed accord-ing to DSM-IV (or ICD-10) criteria, and gives the patient the sick role. The psychiatric history includes the ‘interpersonal inventory’ , which is not a structured instrument but a careful review of the patient’s past and current social functioning and close relationships, their patterns, and mutual expectations. The rela-tionships are examined to see to what extent they are satisfactory, whether there have been recent changes in those relationships, or whether the patient desires to change them. As part of this review, the therapist commonly links the main social and interpersonal situations of the patient’s life to the onset of depressive symptoms.
During the opening phase the therapist also sets a time limit for

During the opening phase the therapist also sets a time limit for 
the acute treatment, generally between 12 and 16 sessions. The optimal number of sessions for IPT requires further research. One study suggests that as few as eight sessions may be effective for some patients, but similar to pharmacological treatment, different doses (i.e. number of IPT sessions) might be necessary for different patients. Sessions are generally scheduled weekly. This allows sufﬁ  -
cient time to pass that things will happen in the patient’s outside life, on which the treatment focuses. Y et it is frequent enough to maintain momentum and thematic continuity. However, in certain cases logistical difﬁ  culties (e.g. due to a general medical illness) 
might require less frequent sessions.
At the end of the ﬁ  rst phase, the therapist links the depressive 
syndrome to the patient’s interpersonal situation focusing on one of the four interpersonal problem areas: (1) grief ; (2) interpersonal

syndrome to the patient’s interpersonal situation focusing on one of the four interpersonal problem areas: (1) grief ; (2) interpersonal 
role disputes ; (3) role transitions ; or (4) interpersonal deﬁ  cits. Once 
the patient explicitly accepts this formulation as the focus for treat-ment, IPT enters its middle phase.
It is important to keep treatment focused on a simple theme. 
Any formulation necessarily simpliﬁ  es a patient’s life narrative. 
Although some patients may present with multiple interpersonal problems, the goal of the formulation is to isolate one or, at most, two salient problems related to the patient’s mood disorder (whether as precipitant or consequence). More than two foci would risk diffusing the treatment and diluting its efﬁ  cacy. Sometimes a 
number of interpersonal problems contribute to the depressive episode, making it apparently difﬁ  cult to choose a focus. However,

number of interpersonal problems contribute to the depressive episode, making it apparently difﬁ  cult to choose a focus. However, 
research has shown that IPT therapists agree in choosing foci, and patients ﬁ  nd those foci credible. Moreover, resolution of the 
interpersonal treatment focus appears to correlate with symptom-atic improvement.
An important task of the initial phase requires deciding 
whether or not to use medication. A growing literature suggests that combined treatment with antidepressants and IPT works at least as well as, but is not always superior to IPT alone. Thus, except for very severe cases or possibly the elderly, the choice between IPT alone or combined with medication relies more on cost, availability 
of resources, and patients’ preference than on existing empirical 
evidence.
The middle phase  involves approaches speciﬁ  c to the chosen 
interpersonal problem area. For Grief —complicated bereavement

evidence.
interpersonal problem area. For Grief —complicated bereavement 
following the death of a loved one—the therapist facilitates mourning and helps the patient ﬁ  nd new activities and relation-
ships to compensate for the loss. Role disputes  are conflicts 
with signiﬁ  cant others: a spouse, a child, other family members, 
co-workers, or a close friend. The therapist helps the patient explore the relationship, the nature of the dispute, and available options to negotiate its resolution, including ending the relation-
ship. Role transition  includes change in life status: for example, 
beginning or ending a relationship or career, moving, promotion, demotion, retirement, graduation, having a baby, or diagnosis of another medical illness. The patient learns to manage the change by mourning the loss of the old role, recognizing positive and negative aspects of the new role, and taking steps to master this new role.

Interpersonal deﬁ  cits  are used as a focus for patients who lack 
any of the ﬁ  rst three focal life situations. Such patients are isolated 
or lack social skills, have problems in initiating or sustaining relationships. The goal is to help the patient to develop new rela-tionships and skills. Some patients who fall into this category may in fact suffer from dysthymic disorder or social anxiety disorder, for which separate strategies have been developed.
The ﬁ  nal phase  of IPT, occupying the last 2–4 sessions of acute 
treatment, builds the patient’s newly acquired sense of indepen-dence and competence by recognizing and consolidating therapeutic gains. Compared to psychodynamic psychotherapy, IPT de-emphasizes termination: it is a bitter–sweet graduation from successful treatment. The sadness of separating from the therapist is contrasted with depressive feelings.
If the patient has not improved, the therapist emphasizes that the

If the patient has not improved, the therapist emphasizes that the 
treatment  has failed, not the patient, and that alternative effective 
treatments, such as medication or other psychotherapies exist. If the treatment has succeeded, the therapist underscores the patient’s competence to function without further therapy by emphasizing that the depressive episode has improved because 
of the patient’s actions in changing a life situation. The therapist 
also helps the patient to anticipate triggers for and responses to depressive symptoms that might arise in the future.
Patients with multiple prior MDE’s or signiﬁ  cant residual symp-

toms, who successfully complete acute treatment but remain at high risk for relapse or recurrence, may contract for maintenance therapy as acute treatment draws to a close. At the end of the treat-ment (acute or maintenance, depending on the case) the patient is also explicitly told that, should depression recur, the patient should immediately seek treatment, just as the patient would do if any other medical illness recurred.
Techniques
Readers new to IPT will ﬁ  nd that much of what we describe below 
sounds familiar and overlaps with other psychotherapies. Thus, on one level, IPT demands few novel skills from therapists and is relatively easy to learn.
The challenges of IPT lie not in the use of any individual

The challenges of IPT lie not in the use of any individual 
technique, but in organizing these approaches to establish and maintain a coherent primary treatment focus and to resist the temptations of digressing into clinical material outside that focus. Additional challenges may arise from ‘unlearning’ reﬂ  exive responses 
from prior training experiences such as making transfer ence-focused 
interventions (for psychodynamic therapists) or identifying automatic cognitions and schemas (for cognitive therapists). In our exposition of strategies and techniques, we focus on major depressive disorder, the ﬁ  rst and still best tested indication for IPT, 
although the same principles may apply to other disorders.
(a) General strategies
IPT is organized around four important concepts.

1321
(i) Psychoeducation
The therapist helps the patient to recognize that the problem is a 
common medical illness, a mood disorder, with a predictable set of symptoms, not the personal failure or weakness of the patient. IPT therapists deﬁ  ne depression as a treatable condition that is not the 
patient’s fault. This deﬁ  nition displaces guilt from the patient to 
the illness, decreases the patient sense of isolation by feeling part of a larger group (those with depression), and provides hope for a response to treatment.
Underscoring this approach, IPT therapists give depressed

Underscoring this approach, IPT therapists give depressed 
patients the ‘sick role’ . This role temporarily excuses them from what their illness prevents them from doing while assigning them the task of working as patients in order to recover their previous healthy role. The resolution of the sick role is to regain the healthy, euthymic role by the end of treatment. The time-limited structure of IPT also energizes patients and protects against regression during treatment.
(ii) Focusing on the positive
IPT therapists take an empathic, supportive, and encouraging stance. They emphasize their patients’ successes, although they also commiserate on their difﬁ  culties. ‘Focusing on the positive’ means 
underscoring positive events; it does not mean ignoring negative

underscoring positive events; it does not mean ignoring negative 
affect. By doing this, IPT therapists may facilitate the therapeutic alliance that is crucial to good outcome. By solving an interper-sonal crisis—a complicated bereavement, a role dispute or transi-tion, or an interpersonal deﬁ  cit—the IPT patient has the dual 
opportunity to improve his or her life situation and simultaneously relieve the symptoms of the depressive episode.
This coupled formula, validated by randomized controlled trials 
in which IPT has been tested, can be offered with conﬁ  dence 
and optimism. Symptomatic relief may correlate with the degree to which the patient solves his or her interpersonal crisis. This ther-apeutic optimism, while not speciﬁ  c to IPT, very likely provides 
part of its power in remoralizing the patient.
(iii) Focus on the present, not the past

IPT deals with current rather than past interpersonal relationships, focusing on the patient’s immediate social context. The IPT thera-pist attempts to intervene in depressive symptom formation and social dysfunction rather than addressing enduring aspects of personality, which are difﬁ  cult to assess accurately during an 
episode of an Axis I disorder. However, IPT does build new social skills such as self-assertion and increased ability to understand interpersonal exchanges, which may be as valuable as changing personality traits.
(iv) Link mood to life events

A core strategy of IPT is constant attention to the link between the patient’s current mood state and recent interpersonal experiences. Stressful life events and negative interpersonal en -counters trigger lower mood and can lead to depressive episodes in vulnerable individuals. Conversely, depressed mood impairs social functioning, which can lead to further negative life events. IPT is postulated to work by helping the patients manage interpersonal relationships more effectively, which leads to improved mood. Improved mood then allows patients to more effectively manage interpersonal experiences in an iterative fashion.
Unlike psychodynamic psychotherapy, IPT does not  focus on 
early childhood experiences and long-standing familial dynamics. Thus, the patient’s current mood state is linked to recent

early childhood experiences and long-standing familial dynamics. Thus, the patient’s current mood state is linked to recent 
experiences rather than those rooted in the distant past. Nor does IPT focus on transferential material, except in the relatively rare instance when problems arise in the therapeutic alliance. Thus the treatment highlights recent experiences outside the ofﬁ  ce.
(b) Speciﬁ  c techniques
T o achieve the general goals of IPT, the following techniques are 
frequently used:
1An opening question : ‘how have things been since we last met?’ , 
which leads the patient to provide an interval history of mood and events. The therapist begins each session after the ﬁ  rst one

which leads the patient to provide an interval history of mood and events. The therapist begins each session after the ﬁ  rst one 
with this tactic. It is common, particularly at the beginning of the treatment that the patient will focus exclusively either on the mood or on a recent event. When that occurs, the therapist gen-tly asks about the other aspect and helps the patient connect mood and recent events.
2Communication analysis , a detailed recreation of recent, 
affectively charged circumstances. This detailed analysis often helps the patient uncover nuances of the interpersonal exchanges 
that had been missed prior to the session.
3 An exploration of the patient’s wishes and options, to help the 
patient realize and voice the desired outcomes.
4Decision analysis , to help the patient integrate communication

4Decision analysis , to help the patient integrate communication 
analysis, the wishes and options and the constraints of the situa-tion and decide on a speciﬁ  c course of action.
5Role-playing , to help the patient rehearse that course of action 
before implementing in real life.
Similarities and differences with 
other psychotherapies
Because IPT and CBT are the two best empirically supported 
psychotherapies, they are often compared. (23) IPT shares with CBT

psychotherapies, they are often compared. (23) IPT shares with CBT 
an orientation towards making the patient feel understood, a ‘here and now’ focus, a general feeling of hope and optimism, psycho-education, and the use of role-playing to favour the acquisition of new skills. It addresses interpersonal issues in a manner familiar to marital therapists. Although like CBT a time-limited treatment targeting a syndromal constellation (e.g. major depression), IPT is considerably less structured, and focuses on interpersonal problem areas rather than automatic thoughts. IPT overlaps to some degree with psychodynamic psychotherapies, yet IPT also meaningfully differs from them: in its focus on the present, not the past; its focus on practical, real-life change rather than self-understanding; its medical model; and its avoidance of the trans-ference and of genetic and dream interpretations.
Efﬁ cacy

Efﬁ cacy
Research ﬁ  ndings: IPT for mood disorders
IPT outcome research is ongoing, with new studies published every 
year. What follows is a selection of key research trials of IPT for mood and other disorders. For some of these trials, IPT was adapted in a separate treatment manual, but in all cases the general principles of the treatment remained the same.6.3.3 interpersonal psychotherapy for depression and other disorders

SECTION 6  treatment methods in psychiatry 1322
(a) Acute treatment of major depression
IPT was ﬁ  rst tested as an acute antidepressant treatment in a four-cell, 
16-week randomized trial. This compared weekly IPT, amitriptyline (AMI), their combination, and a monthly supportive psychotherapy treatment for 81 outpatients with major depression.
(24,25) The out-
come of patients receiving amitriptyline and IPT was similar and superior to that of supportive psychotherapy. Patients who received both amitriptyline and IPT had better depression outcomes and better scores on a range of social adjustment measures including overall adjustment, work performance, and communication than those on amitriptyline alone, suggesting an additive effect of IPT on medication treatment. At 1-year follow-up, many patients sustained improvement from the brief IPT intervention, and IPT 
patients had developed signiﬁ  cantly better psychosocial function-

ing whether or not they received medication. This effect on social function was not found for AMI alone and had not been evident for IPT at the end of the 16-week trial.
Still probably the most important study to date involving 
IPT is the National Institute of Mental Health Treatment of Depression
(24,25) Collaborative Research Program (TDCRP), inves-
tigators randomly assigned 250 outpatients with major depression to 16 weeks of IPT, CBT, or either imipramine (IMI) or placebo with clinical management.
(2) Most subjects completed at least 
15 weeks or 12 treatment sessions. Patients with milder depression (deﬁ ned as a 17-item Hamilton Depression Rating Scale [HDRS]

15 weeks or 12 treatment sessions. Patients with milder depression (deﬁ ned as a 17-item Hamilton Depression Rating Scale [HDRS] 
score <20) improved equally in all four treatments. For more severely depressed patients (HDRS>20), IMI worked fastest and most consistently better than placebo. IPT and IMI were compara-ble on several outcome measures, including HDRS, and superior to placebo for more severely depressed patients. In some analyses, IPT appeared to be slightly superior to CBT. CBT was not superior to placebo among the more depressed patients.
A follow-up study of TDCRP subjects 18 months later found 
no signiﬁ  cant difference in recovery among remitters (who had 
minimal or no symptoms after the end of treatment, sustained during follow-up) among the four treatments.
(26) Thirty per cent

(26) Thirty per cent 
of CBT, 26 per cent of IPT, 19 per cent of imipramine, and 20 per cent of placebo subjects initially randomized to those treat-ments remitted and remained in remission during that time span. Among acute remitters, re lapse over the 18-month follow-up 
was 36 per cent for CBT, 33 per cent for IPT, 50 per cent for imipra-mine (medication having been stopped at 16 weeks), and 33 per cent for placebo. The authors concluded that, for many patients, 16 weeks of speciﬁ  c treatments were insufﬁ  cient to achieve full 
and lasting recovery.
Special populations and settings
(a) Depressed primary care patients

There has been a study comparing IPT and nortriptyline with usual care for depressed patients in a primary care setting. If patients were hospitalized for a general medical condition, IPT was continued in the hospital when possible. Depressive symptom severity declined more rapidly with either nortriptyline or IPT than in usual care. Approximately 70 per cent of treatment completers receiving nortriptyline or IPT, but only 20 per cent in usual care, had recovered after 8 months. Subjects with a lifetime history of comorbid panic disorder had a poorer response across treatments, compared to those with major depression alone.(b) Depressed HIV-positive patients (IPT-HIV)

IPT has also been investigated for depressed HIV patients (IPT-HIV), emphasizing common issues among this population includ-ing concerns about illness and death, grief and role transitions. A randomized study echoing the TDCRP of 101 HIV-positive 
patients with depressive symptoms found IPT and imipramine 
each superior to CBT and supportive therapy. Many patients reported improvement in depressive physical symptoms that they had mistakenly attributed to HIV infection. IPT may have been a better ﬁ  t than CBT for these patients due to the extreme life events 
they faced at the height of the HIV epidemic.
(c) Peripartum depression
Pregnancy and the postpartum also provide natural role transi-tions as an IPT focus. Exploring these role transitions addresses the depressed pregnant woman’s self-evaluation as a parent, physiologic changes of pregnancy and postpartum, and altered relationships with the spouse or signiﬁ  cant other and with other children.

Timing and duration of sessions are adjusted in response to bed-rest, delivery, obstetrical complications, and childcare. Postpartum mothers may bring children to sessions. As with depressed HIV-positive patients, telephone sessions, and hospital visits are some-times necessary. A controlled clinical trial comparing IPT to a didactic parent education group in depressed pregnant women showed advantages for IPT. A study of depressed postpartum women found superiority of IPT over a wait-list control group. A small randomized trial has also suggested the possibility that group IPT may serve to prevent MDD relapse during the postpar-
tum period.
(d)  Conjoint IPT for depressed patients with marital 
disputes (IPT-CM)
Marital conﬂ  ict can precipitate or complicate depressive episodes.

Marital conﬂ  ict can precipitate or complicate depressive episodes. 
Some clinicians believe that individual psychotherapy for patients in marital disputes may lead to premature rupture of marriages. Researchers at Y ale University developed a manual for conjoint therapy of depressed patients with marital disputes (IPT-CM). IPT-CM includes the spouse in all sessions and focuses on the cur-rent marital dispute. Eighteen patients with major depression linked to the onset or exacerbation of marital disputes were randomly assigned to 16 weeks of either individual IPT or IPT-CM. Patients in both treatments showed similar reductions in depressive symptoms, but patients receiving IPT-CM reported signiﬁ  cantly 
better marital adjustment, marital affection, and sexual relations. These pilot ﬁ  ndings require replication with a larger sample and 
other control groups.
(e) Depressed adolescents (IPT-A)

IPT has also been modiﬁ  ed to incorporate adolescent developmental 
issues. Three randomized trials, one of them conducted in Puerto Rico, have shown the efﬁ  cacy of IPT-A. It is important to note that 
in the Puerto Rico study, the only one that also included CBT in the 
design, IPT appeared superior to CBT in certain measures (e.g. 
self-esteem and social adaptation), consistent with the ﬁ  ndings of 
the TDCRP and the study of depressed HIV-positive patients.
(f) Maintenance treatment
Based on the success of IPT as acute treatment for MDD, the 
recurrent nature of mood disorders, and the efﬁ  cacy of medication 
in preventing relapse and recurrence, IPT was adapted as a once

1323
monthly maintenance treatment for MDD (IPT-M). This was a 
novel development and allowed the ﬁ  rst real testing of psychother-
apy as a maintenance treatment for patients who had remitted from acute depression. Since IPT-M begins with patients who have remitted, its goal is to maintain the remitted state. Both patient and therapist are vigilant for early signs of interpersonal problems similar to those of which the patient and therapist previously identiﬁ  ed as associated with the onset of the patient’s most recent 
depressive episode. At the same time, the therapist works to enhance strengths that appear to have been present prior to the patient’s illness or began to emerge as the most recent depressive episode remitted. In contrast with the acute phase application of IPT, which usually focuses on one or at most two interpersonal problem areas, IPT-M may shift problem areas over time. Three studies have compared medication and IPT as maintenance treatment for MDD.

In the ﬁ  rst study, 128 outpatients with recurrent depression 
initially treated with combined high dose (>200 mg/day) imipra-mine and weekly sessions of IPT. 
(4, 5) Responders remained on 
high-dosage medication while IPT was tapered to a monthly frequency during a 4-month continuation phase. Patients who remained re mitted were then randomly assigned to 3 years of either: 
(1) imipramine plus clinical management; (2) imipramine plus monthly IPT; (3) monthly IPT alone; (4) monthly IPT plus place-bo; or (5) placebo plus clinical management.
Both IPT and imipramine were signiﬁ  cantly superior to the 
placebo group in delaying MDD relapse. Imipramine was superior to IPT-M in the ability to prevent relapse. The group that received IPT with imipramine had a numerically lower rate of recurrence at 1 year (16 per cent) than the group on imipramine alone (40 per cent), but those results were not statistically signiﬁ  cant. Two different

studies have had very similar ﬁ  ndings in comparisons of IPT 
and nortriptyline for geriatric patients with recurrent major 
depression. 
(7, 27)
Further study is required to determine the efﬁ  cacy of IPT relative 
to newer medications (e.g. selective serotonin-reuptake inhibitors), and the efﬁ  cacy of dosages other than once monthly maintenance 
IPT. A study of differing doses of maintenance IPT for depressed patients in Pittsburgh has not found differences in outcome based on frequency of sessions.
(28) Perhaps optimal dosing of mainte-
nance IPT depends on individual patients’ needs.
The success of IPT in treating MDD has led researchers to 
investigate its efﬁ  cacy in bipolar and dysthymic disorder.
(i) Bipolar disorder
The modiﬁ  cation of IPT used as an adjunct to medication in the

The modiﬁ  cation of IPT used as an adjunct to medication in the 
treatment of bipolar disorder is called interpersonal and social rhythm therapy (IPSRT). Its use rests on the hypothesis that disruptions of social rhythms are destabilizing for bipolar patients and contribute to trigger their relapse. By decreasing the number and intensity of those disruptions, IPSRT should improve the course of bipolar disorder. The behavioural component helps to protect sleep patterns and limit the disruptions that may provoke mania; the IPT approach to depression remains largely the same.
After stabilizing bipolar I patients with appropriate pharmaco-
therapy and either IPSRT or intensive clinical management, patients were randomized again to either IPSRT or clinical management for preventive treatment.
(6)They found that participants assigned to

(6)They found that participants assigned to 
IPSRT acutely had longer survival times to a new affective episode, irrespective of maintenance treatment assignment. Participants in 
the IPSRT group had higher regularity of social rhythms at the end of the acute treatment, and this increased regularity of social rhythms during the acute treatment mediated the reduced likeli-hood of recurrence during the maintenance treatment. Further research appears necessary to more ﬁ  rmly establish the optimal 
timing and treatment duration of IPSRT.
(ii) Dysthymic disorder
A modification of IPT for dysthymic disorder(29) encourages 
patients to reconceptualiz e what they have considered their lifelong 
character ﬂ  aws as ego-dystonic, chronic mood-dependent symp-
toms: as chronic but treatable ‘state’ rather than immutable ‘trait’ .

Three randomized trials have examined the efﬁ  cacy of IPT in dys-
thymic disorder. In the ﬁ  rst study, 35 patients with an ICD-10 diag-
nosis of dysthymia with or without comorbid MDD were random-ized to moclobemide alone ( n = 19) or moclobemide plus IPT ( n = 
16). Patients were assessed with the 17-item Hamilton Rating Scales for Depression (HAM-D), the Global Assessment Scale (GAS), and the Quality of Life and Satisfaction Questionnaire at baseline, 12, 24, and 48 weeks. Both groups showed statistically signiﬁ  cant improve-
ment in all measures across time. There were no differences between the two treatments at week 12. However, patients in the combined 
group had statistically better scores than the patients in the moclobe-
mide group on all outcome variables at weeks 24 and 48.
In the second study, 707 adults in primary care clinic with DSM-

IV dysthymic disorder were randomized, with or without past and/or current MDD (15 per cent of the sample had current MDD), to treatment with sertraline alone (50–200 mg), IPT alone (10 ses-sions), or sertraline with IPT combined.
(30) At the end of treatment, 
response rates were 60 per cent for sertraline alone, 47 per cent for IPT alone, and 58 per cent for sertraline with IPT. After an addi-tional 18-month naturalistic follow-up phase, there were no statisti-cally signiﬁ  cant differences in symptom reduction between sertra-
line alone and sertraline with IPT. However, both were more effective than IPT alone in reducing depressive symptoms. It is important to note, though, that IPT was given as a brief treatment, while sertra-line was generally continued for the full 2 years of the study.

A third study compared IPT adapted for the treatment of 
dysthymia (IPT-D), brief supportive psychotherapy, sertraline, and combined IPT-D/sertraline for patients with pure dysthymic disor-der (i.e. without ‘double’ depression) in 94 subjects treated over 16 weeks.
(14) Patients improved in all conditions, with the cells 
including sertraline pharmacotherapy showing superiority over psychotherapy alone in response and remission. The results of this study are consistent with an emerging literature suggesting that pharmacotherapy may acutely beneﬁ  t patients more than 
psychotherapy. In conjunction with the other studies in patients with dysthymic disorder, it suggests that IPT alone may not be an efﬁ cacious treatment for dysthymic disorder.
IPT for non-mood disorders
The efﬁ  cacy of IPT as an antidepressant treatment has led to its 
adaptation as a treatment for other psychiatric disorders, based on the premise that life events are ubiquitous.
(a) Bulimia

Fairburn et al. modiﬁ  ed IPT for the treatment of bulimia, eliminat ing 
the use of the sick role and of role-playing in order to contrast 6.3.3 interpersonal psychotherapy for depression and other disorders

SECTION 6  treatment methods in psychiatry 1324
distinct therapeutic strategies in comparing IPT and CBT. Initial 
trials showed that although CBT worked faster to relieve bulimic symptoms, IPT had longer-term beneﬁ  ts comparable to CBT and 
superior to a behavioural control condition.
(1) A subsequent multi-
site trial found CBT superior to IPT.(9)
Following a model closer to the original IPT principles, Wilﬂ  ey 
et al. modiﬁ  ed IPT in a group format (IPT-G) and compared it to 
group CBT and a wait-list control for 56 women with non-purging bulimia.
(8) The initial IPT phase was conducted individually. The 
interpersonal area for almost of all subjects was formulated as ‘interpersonal deﬁ  cits’ . At termination, binge eating decreased in 
the IPT-G and CBT groups, but not in the control condition. Results persisted at 1-year follow-up. A randomized clinical trial of 162 women, comparing group IPT, and CBT for 20 sessions over 20 weeks, yielded similar results.

A research group in Christchurch, New Zealand studied the 
application of IPT to anorexia nervosa.
(19) In their trial, neither 
IPT nor CBT showed efﬁ  cacy as an outpatient treatment, consis-
tent with the general anorexia outcome literature.
(b) Anxiety disorders
IPT has not yet been tested in controlled studies for anxiety disorders. Promising results have been found in for social anxiety disorders, PTSD, and panic disorder.
(22, 31–33)  Several groups are 
currently conducting controlled trials for these disorders.
(c) Substance abuse
IPT has failed to demonstrate efﬁ  cacy in three clinical trials for 
patients with substance dependence.(20, 34, 35) These negative stud-
ies suggest limits to the range of utility of IPT as a main treatment for substance use disorders, but do not necessarily preclude its use to treat MDD comorbidity in those patients.
(d) Other applications

Research groups are testing the applicability of IPT to body dys-morphic disorder, chronic somatization in primary care patients, depressed patients postmyocardial infarction, depressed cancer patients, borderline personality disorder, insomnia, and other disorders. The IPT focus on life events suggests its potential applicability to patients with medical illness.
(e) IPT by telephone
Because many patients avoid or have difﬁ  culty reaching an ofﬁ  ce 
for face-to-face treatment, IPT and IPC are being tested as a treat-ment delivered over the telephone. Weissman and Miller conducted a successful pilot feasibility trial comparing IPT by telephone to wait-list control in 30 patients with recurrent major depression, and found IPT to be the superior control condition in reducing depressive symptoms and improving psychosocial functioning.
(36)

(36)
Neugebauer and colleagues found telephone IPC a helpful inter-vention for women with subsyndromal depression following a miscarriage.
(37, 38)
(f) Interpersonal counselling (IPC)
Many patients presenting for treatment, particularly outside mental health settings, report psychiatric symptoms but do not meet threshold criteria for a psychiatric disorder. Nonetheless, their symptoms can be debilitating, interfering with their daily function-ing, and often result in increased use of general medical services. Interpersonal counselling (IPC), based on IPT, was designed to treat distressed primary care patients who do not meet full syndromal criteria for psychiatric disorders. IPC is administered for a maxi-
mum of six sessions by health care usually by professionals who lack formal psychiatric training such as nurse practitioners. The ﬁ  rst ses-
sion can last up to 30 min; subsequent sessions are briefer.
IPC therapists assess the patient’s current functioning, recent life

IPC therapists assess the patient’s current functioning, recent life 
events, occupational and familial stressors, and changes in inter-personal relationships. They assume that such events provide the context in which emotional and bodily symptoms occur. Klerman and colleagues studied 128 patients in a primary care clinic who scored 6 or higher on the Goldberg General Health Questionnaire (GHQ), randomizing them to IPC or to usual care without psycho-logical treatment.
(39) Over an average of 3 months, often receiving 
only one or two IPC sessions, IPC subjects showed signiﬁ  cantly 
greater symptom relief on the GHQ than controls, especially mood improvement. IPC subjects were more likely to subsequently make use of mental health services, suggesting a new awareness of the psychological aspect of their symptoms.
Predictors of response to IPT

Five studies have examined predictors of response to IPT. Analyses of the TDCRP data identiﬁ  ed general predictors of response to 
MDD treatment, as well as predictors for specific treatment modalities.
(40,41) Seven patient characteristics predicted outcome 
across treatments: social dysfunction (higher social function pre-dicted better response), cognitive dysfunction (better cognitive function predicted better response, particularly to CBT), expecta-tion of improvement (higher expectation predicted better response), therapeutic alliance (a stronger alliance predicted bet-ter response), endogeneity of depression (endogenous depression tended to have better response, a ﬁ  nding supported by another 
study examining the relationship between EEG patterns and response to IPT in depressed patients
(42)), double depression (its

(42)), double depression (its 
presence predicted poorer outcome), personality traits (their pres-ence predicted worse response), and duration of current episode (longer duration was associated to worse response). In addition prior social adjustment, as measured by previous attainment of a marital relationship and higher satisfaction with social relation-ships in general, differentially predicted good response to IPT. This ﬁ  nding is consistent with reports in the general psychothera-
py literature documenting that various indicators higher baseline psychosocial functioning predict good psychotherapy response. Two other studies suggest that comorbidity tends to worsen the prognosis of treatment with IPT alone, but not the prognosis of combined treatment.
(43,44)
Summary of research ﬁ  ndings
IPT has demonstrated efficacy as an acute and maintenance

(43,44)
IPT has demonstrated efficacy as an acute and maintenance 
monotherapy and as a component of combined treatment for major depressive disorder. It also appears to have utility for other mood and non-mood syndromes, although the evidence for these is sparser. It has not shown beneﬁ  t for substance use disorders or as 
a monotherapy for dysthymic disorder. Since monotherapy with either IPT or pharmacotherapy is likely to sufﬁ  ce for most patients 
with major depressive disorder, combined treatment is probably best reserved for severely or chronically ill patients. How best to combine time-limited psychotherapy with pharmacotherapy—for which patients, in what sequence, etc.—is an exciting area for future research.

1325
Training
Until recently, IPT therapists were few, and practiced almost 
exclusively in research studies. Publications supporting its efﬁ  cacy 
have led to clinical demand for this empirically supported treatment. IPT training is now increasingly included in professional work-shops and conferences, with training courses conducted at University centres in Canada, the United Kingdom, continental Europe, Asia, New Zealand, and Australia. IPT is taught in a small but growing minority of psychiatric residency training programmes in the United States and as well as some family practice and primary care training programmes.
Although the principles and practice of IPT are relatively

Although the principles and practice of IPT are relatively 
straightforward, any psychotherapy requires innate therapeutic ability, comfort with the so-called common factors of psychotherapy: tolerating and exploring affect, helping the patient to feel under-stood, engendering hope, etc. IPT training requires more than reading the manual: psychotherapy is learned by doing. Most IPT training programmes are designed to help experienced therapists refocus their treatment by learning new techniques, not to teach novices psychotherapy. Candidates should have a graduate clinical degree (MD, Ph.D., MSW, RN), several years of experience con-ducting psychotherapy, and clinical familiarity with the diagnosis of patients they plan to treat.
The IPT training in the TDCRP became the model for subsequent 
research studies. It included a brief didactic programme, reading the manual, and a practicum in which the therapist treated 2–3 patients under close supervision monitored by videotapes of the

research studies. It included a brief didactic programme, reading the manual, and a practicum in which the therapist treated 2–3 patients under close supervision monitored by videotapes of the 
sessions. For research certiﬁ  cation, we continue to recommend at 
least two or three successfully treated cases with hour for hour supervision of taped sessions.
Although many clinicians would like a formal certificate 
or diploma in IPT, there is no gold standard of IPT proﬁ  ciency 
and no accrediting board. When IPT practice was limited to research settings, this posed no problem: one research group taught another, in the manner described above. As IPT spreads in clinical practice, the educational and accreditation process for IPT requires further study. The newly created International Society for Interpersonal Psychotherapy (ISIPT) may provide an appropriate forum in which to discuss these increasingly important issues.

The history of IPT has been a succession of outcome trials. These studies have helped to deﬁ  ne diagnostic indications for this treat-
ment, but we know far less about the dosage and indications of IPT than about antidepressant medication. Future outcome trials may continue to deﬁ  ne the scope of efﬁ  cacy (response to treatment 
under ideal conditions) and effectiveness (response to treatment in more general clinical settings) of IPT. These should include both tests for different diagnoses, such as the anxiety disorders, testing of dosage—optimal frequency and duration of IPT sessions—and also studies of the sequencing of IPT with other treatments. Other research may help to determine the cost-effectiveness and potential cost-offset of IPT as a treatment that improves both symptoms and social functioning.
Most of the work on IPT to date has focused on treatment out-
come. By contrast, little is known about the process aspects in IPT

come. By contrast, little is known about the process aspects in IPT 
such as the speciﬁ  c value of many IPT interventions. Although it appears that solving an interpersonal problem area correlates 
with treatment outcome, it is unclear, for example, whether the choice of a particular treatment focus over other makes a difference for patients, or whether particular sorts of life events are helpful or unhelpful foci. Patient and therapist characteristics may also 
potentially inﬂ  uence treatment outcome.
Finally, while the initial work on IPT was conducted in the United 
States, over the last few years, IPT trials have also been conducted in other countries. As those studies continue to be conducted, it will become easier to discern to what extent IPT addresses topics are universal across cultures.
In summary, IPT is a time-limited, forward-looking, pragmati-

cally focused psychotherapy that deﬁ  nes psychiatric disorders as 
treatable medical illnesses and links them to the patient’s current social situation. This strategy has proved efﬁ  cacious for patients 
with major depression and bulimia, and shows promise for other mood and non-mood disorders.
Elkin, I., Shea, M.T., Watkins, J.T., et al. (1989). National Institute of 
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Weissman, M.M., Markowitz, J.C., and Klerman, G.L. (2007). Clinician’s 
quick guide to interpersonal psychotherapy . Oxford University Press, 
New Y ork.
Website of the International Society of Interpersonal Psychotherapy:

New Y ork.
Website of the International Society of Interpersonal Psychotherapy: 
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interpersonal psychotherapy for patients with dysthymic disorder in primary care: 6-month comparison with longitudinal 2-year follow-up of effectiveness and costs. Journal of Affective Disorders ,
68(2–3), 317–30.
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153(10), 1293–300.

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6.3.4 Brief individual 
psychodynamic psychotherapy
Interest in brief dynamic psychotherapy has ﬂ  ourished in recent 
years. The psychodynamic psychotherapies, including brief psy-chodynamic psychotherapy, aim to change behaviour through new understanding and the recognition of maladaptive patterns of behaviour enacted since childhood but not previously observed. Through this process, perceptions, expectations, beliefs, and, there-fore, behaviours and feelings are altered.
(1)
Historically, ‘brief psychotherapy’ and ‘long-term psychotherapy’ 
were used synonymously with ‘supportive’ and ‘explorative’ psychotherapy, respectively. However, brief and long-term describe only the duration rather than the technique, focus, or goal of treatment.
(2) The time limits of brief dynamic psychotherapy give

(2) The time limits of brief dynamic psychotherapy give 
it a unique character and distinguish it from long-term psycho-therapy and psychoanalysis. Because of its limited goals, the brief dynamic psychotherapist must confront his or her ambitiousness and perfectionism as well as any exaggerated ideal of personality structure and function.
Psychotherapy in general, and brief individual psychodynamic 
psychotherapy in particular, is perhaps the most elegant form of micro-neurosurgery. Psychotherapy strives to alter behaviour (i.e. cognitions, affects, and actions) with verbal interchange—fundamentally to change neurone A that used to connect to neurone B so it will now connect to neurone C. Although the ther-apist in the individual psychodynamically derived psychotherapies does not ‘require’ behavioural change, the end result of the thera pist’s

technical expertise is to achieve behavioural change, including changes in well-being, physical health, social supports, and societal productivity as well as symptomatic relief. As in all of medicine, 
both non-speciﬁ  c and speciﬁ  c curative factors affect the outcome 
of this work. The non-specific curative factors—abreaction, the provision of new information, and maximizing success experiences—are present in all forms of medical treatment includ-ing brief psychotherapy. Brief individual dynamic psychotherapy also has speciﬁ  c technical interventions and procedures above 
and beyond the non-speciﬁ  c curative factors. As in other medical 
therapies, there are contraindications and dangers in the use of this treatment.

Evolving from psychoanalysis in the mid-twentieth century, brief individual psychodynamic psychotherapy, like other psychody-namic treatments, is based on the principle that meanings and past experience play an important role in behaviour and illness. Although psychoanalysis is now a lengthy procedure usually requiring a number of years to complete, the early psychoanalytic literature, including Freud’s ﬁ  rst cases, contain histories of success-
ful short analyses. During the ﬁ  rst 30 years of psychoanalysis, it was 
unusual for treatments to extend beyond 1 year.
(3) Ferenczi was the 
ﬁ rst analyst to advocate shortening psychoanalysis. He advocated ‘active therapy’ a more directive, focused, and briefer treatment. 
Rank was the ﬁ  rst one to explicitly to set a time limit on treatment.

Rank was the ﬁ  rst one to explicitly to set a time limit on treatment. 
Ferenczi and Rank(4) articulated the advantages of brief dynamic 
Following the Second World War, the interest in psychoanalysis 
resulted in greater demand for psychotherapy and increased pressure to develop briefer treatments. In the mid-1940s, Alexander and French advocated shortening treatment by decreasing the frequency of sessions in order to minimize regression. They pro-posed to focus treatment on the present rather than the past, using historical conﬂ  icts to inform the therapist in providing the best 
corrective emotional experience for the patient in the present.
The community-based mental health treatment movement, the 
increasing cost of mental health care, and the rise of managed care in the United States; have stimulated efforts to ﬁ  nd briefer forms

increasing cost of mental health care, and the rise of managed care in the United States; have stimulated efforts to ﬁ  nd briefer forms 
of psychotherapy. Contemporary brief individual psychodynamic psychotherapy is heavily influenced by the British School’s development of brief focal psychotherapy. Balint sponsored a workshop of experienced psychoanalytic psychotherapists, which focused on clinical evaluation and attempted to understand which patients might be suitable for briefer treatment. After Balint’s death, Malan carried on the work of the group. At the Tavistock clinic, Malan developed and applied the principles of psychody-namic treatment to brief treatment, delineating methods for evaluating process and outcome variables. He emphasized the importance of therapeutic planning and the identiﬁ  cation of a 
focal conﬂ  ict.
Concurrently, Sifneos, at the Massachusetts General Hospital, 
was studying brief psychotherapy.

(5,6) Sifneos developed ‘short-
term anxiety-provoking psychotherapy’ as a technique and theory with strict inclusion and exclusion criteria for choosing patients. Davanloo broadened the focus of the brief psychodynamic psycho-therapies to include more than one conﬂ  ict. He also expanded the 
inclusion criteria to individuals with character pathology and chronic phobic and obsessional neuroses, and advocated actively confronting resistances. Mann’s time-limited psychotherapy iden-tiﬁ ed a central issue related to the meaning of time, as the focus of 
the treatment. Mann related this to the patient’s difﬁ  culties in con-
fronting loss and separation and the reality of time and death.
In recent years, brief psychotherapy has become increasingly

In recent years, brief psychotherapy has become increasingly 
research based. Strupp, Luborsky, and Horowitz have all introduced manualized focused psychodynamic treatments which substantially 
contribute to our research understanding of this treatment 
modality.
Brief dynamic psychotherapy technique
(a) Evaluation and setting
The evaluation is particularly important in brief individual 
psychodynamic psychotherapy because of the need for rapid and 
accurate assessment. In contrast to longer term treatments, brief

accurate assessment. In contrast to longer term treatments, brief 
individual psychodynamic psychotherapy does not offer the luxury of time to re-evaluate and correct mistakes. Although at times we think of psychotherapy as beginning as soon as the doctor sees the patient, this is a hyperbole, used to underscore the impor-tance of interpersonal and transferential elements in the initial meeting with the patient. In fact, it is extremely important, particu-larly in brief individual psychodynamic psychotherapy, to distinguish the diagnostic interviews from the ongoing treatment. 6.3.4 brief individual psychodynamic psychotherapy

SECTION 6  treatment methods in psychiatry 1328
The interventions and technical procedures performed during the 
evaluation phase, usually one to four sessions, are substantially dif-ferent from the technical aspects of brief individual psychodynamic psychotherapy itself. The evaluation phase includes the diagnosis, consideration of the interaction among the patient’s ego strength, physical health, and selection variables, and the treatment recom-mendation, including considering the option that no treatment is indicated.
As in all medical treatments, brief individual psychodynamic

As in all medical treatments, brief individual psychodynamic 
psychotherapy is given to patients rather than to diseases. The abil-ity to participate in brief individual psychodynamic psychotherapy process requires the patient to be able to access his or her fantasy life in an active and experiencing manner (i.e. psychologically minded) and, importantly, is able to get up and leave this process behind at the end of a session and not be lost in reverie or uncon-trolled fantasies or fears. Note that this does not mean the patient requires a ‘high IQ’ . In fact, a high IQ, when accompanied with rigidity, intellectualization, and rumination, as is often seen, can be a contraindication to a brief psychodynamic treatment since these defences can be quite formidable. The availability of interper-sonal support in the patient’s real environment and the patient’s ability to experience and simultaneously observe highly charged

affective states are necessary to a successful treatment. Individuals 
who are in an emergent crisis (e.g. imminently suicidal, psychotic, recent major life trauma) and therefore are very concerned and focused on the real events in their life cannot enter into a brief psychodynamic psychotherapy without ﬁ  rst having a period of 
supportive treatment. A true life crisis does not allow the patient the opportunity to explore fantasies.
Negotiation with the patient is an important part of reaching a 
treatment decision in brief individual psychodynamic psychotherapy. The patient must rapidly feel a part of the treatment and commit-ted to the process. The process of setting a time limit at the begin-ning of the treatment can be an important element in decreasing the dropout rate from this form of treatment,
(7) particularly with

(7) particularly with 
the patient who is concerned about dependency, ‘becoming addicted’ to the therapist, or who needs to maintain a substantial sense of control. What is dealt with in treatment can only be what the patient is able to bring into focus, what the patient can tolerate talking about, and what he or she can tolerate the therapist talking about.
(8) Although this is not different than other psychodynamic 
treatments, the limited time of brief individual psychodynamic psychotherapy means that there is limited ability to interpret multiple defences that might open new areas of exploration.
(b) Technique
The rapid establishment of the therapeutic alliance is critical to brief individual psychodynamic psychotherapy.
(9) Identifying the 
patient’s initial anxieties related to beginning therapy is an impor-

tant technique in the early sessions of brief individual psychody-namic psychotherapy in order to assure the alliance and to establish the conditions under which the patient can favourably hear and respond to the interpretations that the therapist will later give. As the therapy unfolds, the therapist operates on the hypothesis that each session is related to the previous one. The therapist strives in each session to identify the continuity of meaning related to the treatment focus that is present but hidden.
(10) This continuity 
is driven by the ‘experience bias’ of the patient, and his or her 
tendency to experience the world in a certain way due to unique developmental experiences that have moulded his or her percep-
tion, interpersonal beliefs, and expectations.(11)
Brief individual psychodynamic psychotherapy is more focused,

Brief individual psychodynamic psychotherapy is more focused, 
and more ‘here and now’ oriented with fewer attempts to recon-struct the developmental origins of conﬂ  icts than the extensive 
reworking of personality undertaken in longer term psychothera pies. 
Through the exploration of the patient’s metaphors and symbols, both defensive patterns and disturbances in present interpersonal relations are identiﬁ  ed in the treatment setting as well as in the 
patient’s life. The importance of being able to hear what the patient has to say and to understand its meaning remains central as in other psychoanalytically oriented treatments.
Free association and inquiry : Free association is part of the

Free association and inquiry : Free association is part of the 
technique of brief individual psychodynamic psychotherapy. But what constitutes free association—as in all dynamic therapies—requires thoughtful consideration. In its most basic form, and particularly highlighted in brief individual psychodynamic psycho-therapy, free association means that the patient is free to choose what they wish to talk about. This rather direct deﬁ  nition empha-
sizes that free association is always relative. In addition, in brief dynamic psychotherapy, the patient is always somewhat more task focused that in open-ended treatments or psychoanalysis and this focus should not be discouraged by the therapist. Rather it is the therapist’s task to hear the themes in the patient’s concerns. The therapist asks questions, directs the patient’s attention, and uses 
benign neglect, i.e. avoids some areas of conﬂ  ict that cannot be

benign neglect, i.e. avoids some areas of conﬂ  ict that cannot be 
dealt with at this time or in a short period of time. The therapist identiﬁ  es those spots at which free association breaks down (the 
presence of a defence) or at which the narrative is carrying a single emotional story out of the patient’s awareness. As in all dynamic treatments, often when the patient is able to talk freely and with a coherent narrative about their conﬂ  icts, the work of the treatment 
is completed.
Defence and transference : Brief individual psychodynamic 
psychotherapy emphasizes understanding (a) the mechanisms of defence used by the patient to decrease anxiety and other uncom-fortable feelings associated with areas of conﬂ  ict which are out of

awareness, and (b) the characteristic transference relationships which distort the patients response to their adult world. Typically these two areas, defence and transference, create the world of meaning and expectations in which the patient lives. The tech-niques of the brief psychodynamic psychotherapy are directed towards clarifying these areas and presenting them to the patient to increase understanding and in this manner change symptoms and behaviour. Often only one defence is concentrated on in a given brief treatment. As the defence is clarified, the transference relationship may become evident. The developmental narrative of how the patient came to see the world in the way he or she does, provides the ‘glue’ through which the patient can integrate this knowledge into their life experience and behaviours, and recall it for practice and future use.
The brief individual psychodynamic psychotherapy therapist, 
similar to longer term psychodynamic work, must both enhance

similar to longer term psychodynamic work, must both enhance 
the patient’s observing capacity in order that the transference can be observed by the patient and therapist, and create the therapeutic situation in which the patient can hear the therapist’s interpreta-tions in a useful manner. Dreams, as well as slips of the tongue 
and symptoms, can provide an avenue to the understanding of unconscious conﬂ  ict which can be taught and explored with the

1329
patient. The therapist strives to interpret both the triangle of 
anxiety (wish-defence-anxiety) and the triangle of insight (trans-ference ﬁ  gure in the present—the therapist/patient interaction—
transference ﬁ  gure from the past).
Frequently, when the transference  is most evident, other elements

Frequently, when the transference  is most evident, other elements 
of the past are simultaneously experienced in the patient’s life. In brief individual psychodynamic psychotherapy these can be particularly important to the patient’s understanding the feeling elements of the transference in a mutative manner since the depth and intensity of the transference is much less and much briefer than in long-term work. In contrast, however, the presence of a recent precipitant to the patient’s problems, as is usually the case in brief psychodynamic psychotherapy, can considerably intensify transference responses and be a central element in developing the psychodynamic understanding for the patient. The transference experience—the transference, the life experiences being relived, and particularly the precipitant—provide the web of meaning that is the focus of interpretation and the mutative force in brief individual psychodynamic psychotherapy.

Often the transference in brief individual psychodynamic 
psychotherapy is paternal or maternal, but it has also been noted that, perhaps due to the time-limited nature of the work, sibling 
and transference ﬁ  gures from adolescence may more often be 
recalled in brief individual psychodynamic psychotherapy. The transference is rarely as deep as that seen in long-term treatment. It requires a skilled eye to note and bring the transference to the attention of the patient in a manner that is neither intrusive nor offensive.
(12) Interpretations usually occur over several sessions, in

(12) Interpretations usually occur over several sessions, in 
the middle or later third of the treatment, during which past, pres-ent, and transference experiences are linked together. In the context of the affective arousal associated with this transference experience and the simultaneous understanding of the experience, behavioural change occurs and the patient’s ability to perceive previously hid-den feelings and relationships as well as his or her view of the future and the past can change.
Countertransference : Countertransference is also an important 
element in brief individual psychodynamic psychotherapy as in other psychodynamic treatments.
(13) Analysis of countertransfer-

ence reactions can allow the therapist to recognize subtle aspects of the transference relationship and to understand the patient’s experience better. Because of the more active stance, the brief psy-chodynamic psychotherapist can be particularly prone to counter-transferences that show up as over-involvement or aggression. In addition, the brief time available for treatment can make recovery from countertransference errors quite difﬁ  cult.
(c) Medication
Medication is frequently used in conjunction with brief psychody-

namic psychotherapy. This can complicate the treatment and its progress as well as aid in symptom recovery. The therapist must explore the meaning of the medication and its role in the patient’s view of himself or herself and interpersonal strengths and vulner-abilities. At times, brief individual psychodynamic psychotherapy can also serve as an alternative to medication treatment for less severe symptoms or when medication is contraindicated. Medication may have also begun during the initial brief psychody-namic psychotherapy and then continued after the psychotherapy has formally stopped and the patient is followed with less frequent meetings to monitor medication. This sequence has many advantages including resolving present stressors and precipitants,

encouraging medication compliance, and ongoing medical follow-up after therapy either in maintenance or intermittent frequency. Another course of brief dynamic therapy may be indi-cated at a later date if the response to combined treatment is ineffective or if new problems appear. Greater education of clini-cians and research on this combined and sequential treatment is needed.
Comparison of the brief psychodynamic 
The work of Malan, Sifneos, Mann, and Davanloo shows substan-
tial overlap in each author’s goals, selection criteria, technique, and duration of treatment.
(14) The goals of all of these models of 
brief psychotherapy include facilitating health-seeking behaviours and mitigating obstacles to normal growth. From this perspective, brief psychotherapy focuses on the patient’s continuous develop-ment throughout adult life and the context-dependent appearance of conﬂ  ict, depending on environment, interpersonal relationships,

biological health, and developmental stage. This picture of brief psychotherapy supports modest goals that require the therapist to refrain from perfectionism. Malan, Sifneos, Mann, and Davanloo also seem to agree with Stierlin’s
(15) contrast between brief psycho-
therapy’s use of the ‘propitious moment’ and long-term treatment’s use of ‘a shared past’ between therapist and patient. Both the propitious moment and the shared past carry psychotherapeutic advantages and disadvantages, emphasizing certain technical possibilities and limiting others.
Selection criteria : Many of the selection criteria emphasized by

Selection criteria : Many of the selection criteria emphasized by 
Malan, Sifneos, Mann, and Davanloo are common to all kinds of psychodynamic psychotherapy. However, unique selection criteria are required due to the brief duration of treatment. Patients in brief psychodynamic psychotherapy must be able to engage quickly with the therapist, terminate in a short period of time, and be able to carry on much of the working through and generalizing of the treatment effects on their own.
The necessity for greater independent action by the patient 
requires that the patient have high levels of ego strength, motivation, and responsiveness to interpretation. Sifneos’s rather unique emphasis on intelligence as a criterion may be related to his anxiety-provoking interpretations, which require a broader educational context in order to be understood. The importance of the rapid establishment of the therapeutic alliance underlies a substantial number of the selection and exclusion criteria.

Focus of brief psychotherapy : All authors mention the central 
importance of the focus in brief psychotherapy, and therefore the evaluation sessions to determine this focus. Mann formulates the focus to the patient in terms of the patient’s fears and pain. However, he would probably agree with Malan, Davanloo, and Sifneos in the importance of constructing the psychodynamic focus at a deeper level in one’s own understanding of the work being done. Maintaining the focus is the primary task of the therapist. This enables the therapist to deal with complicated personality struc-tures in a brief period of time. Resistance is limited through benign neglect of potentially troublesome but non-focal areas of the personality. The elaboration of techniques for establishing and maintaining the focus of treatment is critical to all brief individual psychodynamic psychotherapies.6.3.4 brief individual psychodynamic psychotherapy

SECTION 6  treatment methods in psychiatry 1330
Transference : The manner and rapidity in which transference 
is dealt with vary considerably among proponents of brief individ-ual psychodynamic psychotherapy. Malan takes a more typical psychoanalytic approach of waiting for transference to become resistance before it is interpreted. Sifneos, in his emphasis on the Oedipal relationship, is more aggressive in handling the deep con-ﬂ ictual areas of transference material. Davanloo is confrontational 
in developing a transference experience. This confrontational style may at times confuse the patient’s experience of the real and the transferential therapist. However, Davanloo often treats severe obsessional disorders. In these cases, the need to increase the patient’s affective awareness is high. These may be the patients in which this particular technique is most useful. Aggressive, compet-itive, and hostile feelings, which might otherwise remain ﬁ  rmly

defended, may thus become available to these patients.
Countertransference : The role of countertransference in brief 
psychotherapy is as complicated as it is in long-term treatment. Countertransference issues related to the aggressive techniques used by Sifneos and Davanloo have been observed. Countertransference experiences related to termination and loss can also be prominent.
(16)
The goal-directed techniques of brief psychotherapy limit the development of regressive countertransference responses.
(13)
Duration of treatment : There is remarkable agreement on the 
duration of brief psychotherapy. Although the duration ranges from 5 to 40 sessions, authors generally favour 10 to 20 sessions. The duration of treatment is critically related to maintaining the focus within the brief psychotherapy. Shlien et al.
(17) have found in

(17) have found in 
Rogerian therapy, a correlation between the number of sessions and recovery. In general, they report an increasingly successful outcome (measured by the patient’s self-concept) up to about 20 sessions. Howard et al .
(18) using a meta-analytical technique, 
found 75 per cent of patients showing some improvement by 26 sessions. However, this study includes a wide range of types of treatment. When treatment extends beyond 20 sessions, the thera-pist frequently may ﬁ  nd himself or herself enmeshed in a broad 
character analysis without a focal conﬂ  ict. Change after 20 sessions 
may be quite slow. Clinical experience generally supports the idea that brief individual psychodynamic psychotherapy should be between 10 and 20 sessions although more complicated cases will require greater length of treatment. Often extending treatment beyond 20 sessions is recognition that treatment will be beyond 40 or 50 sessions.

Brief psychodynamic psychotherapy for depression, narcissistic 
disturbances, panic disorder, substance abuse, and post-traumatic 
stress disorder have been described.
(14,19) Horowitz et al.(20) have 
described brief psychotherapy focused on the stress responses evidenced by various personality styles. He emphasizes that this psychotherapy is directed towards dealing with the process of the stress response and not character change. However, his outcomes 
indicate that selected character changes are possible in some areas. 
The distinction between recovery from a disruption in homoeo-static balance, reconstitution of self-esteem and self-concept, and changes in character structure require further exploration.
Critical points : The identiﬁ  cation of critical points during brief 
psychotherapy, when the ‘danger’ of becoming a long-term treat-ment is most acute, clariﬁ  es the technical handling of brief psycho-

dynamic psychotherapy. At these points, the therapist often notes an increasing vagueness of the goals of the treatment, decreased activity by the therapist, and the emergence of the transference as the central element. These variables indicate the potential of a 
short-term psychotherapy becoming a long-term treatment. The fourth to sixth hour of weekly 12-session therapy is often a point at which incipient or potential regression may suddenly appear. The patient at this time is testing the boundaries of the treatment. Action by the therapist is required if a brief psychotherapy is to remain exactly that—brief. The study of technical interventions, which occur at these critical moments, will further elucidate the technical handling of limited regression in brief psychodynamic psychotherapy.

Malan and the T avistock group: focal psychotherapy : Developed 
from the workshops of Balint and Malan, focal psychotherapy is an example of applied psychoanalysis.
(21) Malan has carried on Balint’s 
earlier work.(22, 23)  Previous attempts to develop brief forms of psy-
choanalytic psychotherapy primarily involved the use of ‘activity’ which was frequently equated with manipulation. On the contrary, Malan emphasized the importance of choosing and maintaining a narrow focal area to be dealt with in a brief period of time. He stresses the importance of ﬁ  nding the appropriate focus in the 
patient’s story and consistently interpreting the focal problem area.
(23) Through selective attention and neglect, the therapist 
maintains the focus and completes a brief psychotherapy. The importance of determining the focus underscores the value of the diagnostic process, including the psychodynamic assessment of the patient prior to the initiation of psychotherapy.
(24)

(24)
Malan identiﬁ  es the following factors as leading to the lengthen-
ing of treatment: resistance, overdetermination, a need for working through the roots of conﬂ  ict in early childhood, transference, 
dependence, negative transference connected with termination, and the transference neurosis. In addition, some therapist charac-teristics may lengthen treatment. These include a tendency towards passivity, a sense of timelessness conveyed to the patient, therapeu-tic perfectionism, and a preoccupation with deeper earlier experi-ences. All of these factors must be dealt with in order to maintain a brief therapy. For Malan, identifying a focal conﬂ  ict acceptable 
to the patient is critical to a successful outcome (Table 6.3.4.1). In addition, the patient must have the capacity to think in feeling terms, demonstrate a high motivation, and exhibit a good response to trial interpretations made during the evaluation phase. Patients

who have had serious suicidal attempts, drug addiction, long-term 
Table 6.3.4.1  Brief psychodynamic psychotherapies
Goal of treatment
Identify the defence, the anxiety, and the impulse
Link the present, the past, and the transference
Focus of treatment
Internal conﬂ  ict present since childhood
Selection criteria
Patient is able to think in feeling terms
Highly motivated
Good response to trial interpretation
Duration of treatment
Up to 1 year
Mean 20 sessions
Termination
Set deﬁ  nite termination date at beginning of treatment

1331
hospital stays, more than one course of electroconvulsive therapy, 
chronic alcoholism, incapacitating severe chronic obsessional symptoms, severe chronic phobic symptoms, or gross destructive or self-destructive acting-out are excluded from treatment. The patient is also excluded from focal psychotherapy if the therapist anticipates any of the items in Table 6.3.4.2.
For Malan, the criteria in Table 6.3.4.2 represent speciﬁ  c dangers. 
If the therapist cannot make contact with the patient, or low motivation or rigid defences are present, it will be difﬁ  cult to form 
an effective therapeutic working alliance within a short time. Complex or deep-seated issues, which must be dealt with to resolve a conﬂ  ict area, require a longer period of treatment. Difﬁ  cult trans-

ference relationships may also prevent timely termination or lead to premature termination. The occurrence of severe depressive or psychotic episodes during treatment can be a danger to the patient and require adjunctive treatments. Thus, Malan takes seriously the time limitation in brief therapy, which requires the rapid establish-ment of a therapeutic alliance and the ability to terminate therapy without the development of unexpected serious symptoms.
Malan, in contrast with other practitioners, does not automati-
cally exclude patients with serious psychopathology. He sees the balance between motivation and focality as the primary criteria. A patient with only moderate motivation but a highly focal conﬂ  ict 
might be accepted into treatment. Similarly, a patient with high motivation but not as focal a conﬂ  ict might also be accepted into 
treatment with the hope that clariﬁ  cation of the focus would occur 
in a short period of time.

Identifying the precipitating factors, early traumatic experiences, 
or repetitive patterns can indicate the area of internal conﬂ  ict 
present since childhood and the possible focus of treatment. The therapist should assess the congruence between the current conﬂ  ict 
and the ‘nuclear’ or childhood conﬂ  ict during the evaluation phase. 
The patient’s response to interpretations about aspects of this conﬂ  ict may lead to acceptance into treatment. According to Malan, 
the greater the probability that the conﬂ  ict area will manifest itself 
in the transference, the more positive the outcome will be.
Malan is less concerned with technique than with the impor-

tance of choosing the focus. He employs the usual technical procedures of psychoanalytic psychotherapy and emphasizes the importance of making interpretations of the transference and con-necting these to current and past relationships. This ‘triangle of insight’ (the transference, the current relationship, and the past relationship) leads to the patient’s cure. Overall, the goal is to clarify the nature of the defence, the anxiety, and the impulse, which the patient is experiencing, and to link these to the present, the past, 
and the transference. Once the defence and the anxiety are clari-ﬁ ed, the link to the past can be made. The interpretation that links 
to the past may be experienced as reassuring by the patient because of its emphasis on the conﬂ  ict belonging to the world of fantasy

to the past may be experienced as reassuring by the patient because of its emphasis on the conﬂ  ict belonging to the world of fantasy 
rather than to the world of the present. Malan emphasizes tran-sference interpretations as the most therapeutically effective interpretations because of their ‘here and now’ character.
In the brief therapy unit at the Tavistock Clinic, a time limit 
was almost always given at the beginning of treatment. For trainees 
this was usually 30 sessions. However, in his publications, Malan 
indicates a mean of 20 sessions for those cases with favourable outcomes. The longer time for trainees gives the opportunity to correct mistakes that might occur. In some published cases, therapy was extended up to 1 year (46 sessions). In general, Malan advo-cates the importance of a deﬁ  nite date rather than a number of

sessions. Practically speaking, this eliminates the need for the patient and therapist to keep count of the number of sessions and eliminates complications related to whether or not to make up sessions that the patient has missed. Such a time limit gives a deﬁ nite beginning, middle, and end to the therapy. It helps to con-
centrate the patient’s material and the therapist’s work, to maintain the focus, and decrease the diffuseness that might lead into long-term work.
Sifneos: short-term anxiety-provoking psychotherapy:  Sifneos

Sifneos: short-term anxiety-provoking psychotherapy:  Sifneos 
emphasizes the importance of patient selection because of the anxiety-provoking nature of his brief psychotherapy techniques (Table 6.3.4.1). He distinguishes anxiety-provoking therapy from anxiety-suppressing therapy, commonly referred to as supportive psychotherapy. For short-term anxiety-provoking psychotherapy, the patient must be of above average intelligence and have had at least one meaningful relationship with another person during his or her lifetime. The patient who has had such a relationship will be able to withstand the anxiety produced by the therapy and to develop rapidly a mature collaborative relationship with the therapist. This criterion tends to exclude narcissistic disorders. In addition, the patient must be highly motivated for change, not only for symp-tom relief. Sifneos also identiﬁ  es several criteria for the patient 
selection based on the presentation of the patient during the evalu-

ation. The patient must have a speciﬁ  c chief complaint. If the 
patient has a number of complaints, Sifneos asks the patient which complaint is of top priority. The patient’s ability to identify one conﬂ  ict area and to postpone work on others is taken as an indica-
tion of the patient’s ability to tolerate anxiety. Sifneos looks for patients with anxiety, depression, phobias, conversion, and mild obsessive-compulsive features or personality disorders involving clear-cut interpersonal difﬁ  culties. During the evaluation, the 
patient must show an ability to interact with the evaluating psychiatrist, to express feelings, and to show some ﬂ  exibility.
Sifneos is one of the few authors who clariﬁ  es his assessment of 
motivation. He deﬁ  nes motivation as including the patient’s ability

motivation. He deﬁ  nes motivation as including the patient’s ability 
to recognize symptoms as psychological, a tendency to be intro-spective and honest about emotional difﬁ  culties, and a willingness 
to participate in the treatment situation. In addition, motivation includes curiosity, willingness to change as well as a willingness to make reasonable sacriﬁ  ces, and a realistic expectation of the results 
of psychotherapy.
Sifneos focuses on the Oedipal conﬂ  ict and does not expect a 
good outcome in dealing with other than Oedipal conﬂ  ict areas. Table 6.3.4.2  Exclusion criteria for Malan’s and the Tavistock group’s 
brief focal psychotherapy
1.  Therapist is unable to make affective contact with the patient during the 
evaluation

2. Therapist anticipates that extended work will be needed To generate motivation To decrease rigid defences To reach complex or deep-seated issues  To resolve unfavourable, intense transference, or dependence which may 
develop
3.  Depressive or psychotic disturbance may intensify and place the patient 
at risk6.3.4 brief individual psychodynamic psychotherapy

SECTION 6  treatment methods in psychiatry 1332
The majority of failures using short-term anxiety-provoking 
psychotherapy have occurred in patients who complained of reac-tive depression following the loss of a loved one. He believes that this failure is due to the non-triangular (non-Oedipal) origins of the ambivalent feelings in some patients. In such cases, when the issue of termination arises, the patient regresses and an impasse is reached.
During the initial phase of psychotherapy, the therapist must 
establish good rapport with the patient in order to create a therapeu-tic alliance. The therapist uses anxiety-provoking confrontations in order to clarify issues around the patient’s early life situation and present-day conﬂ  ict. The therapist avoids areas such as passivity, 
dependence, and acting-out, which might lead to extensive regres-sion. The use of anxiety-provoking confrontations in a direct attack on the patient’s defences dist inguishes short-term anxiety-p rovoking

psychotherapy from other brief psychotherapies. Although it is made clear to patients during their evaluation that the psychother-apy is expected to last only a few months, no speciﬁ  c number of 
sessions or termination date is given. Interviews are held weekly and last for 45 min. The vast majority of treatments last from 12 to 16 sessions, and none go beyond 20 sessions. The aggressive confrontational style of this treatment underscores the importance of excluding pre-Oedipal problems and the importance of coun-tertransference reactions in the therapist related to being too aggressive.
Mann: time-limited psychotherapy:  Mann has focused on the 
speciﬁ  c limitation of time in brief psychotherapy. Mann sees the 
variable of time as a speciﬁ  c operative factor in psychotherapy as 
well as an element in its curative effect.
(25,26) The experiences of 
the timelessness of treatment and of the treatment’s termination are signiﬁ  cant elements in Mann’s view of the psychotherapeutic

the timelessness of treatment and of the treatment’s termination are signiﬁ  cant elements in Mann’s view of the psychotherapeutic 
process.
Usually there are two to four evaluation meetings prior to begin-
ning psychotherapy. Mann limits psychotherapy to a total of 12 treatment hours, distributed according to patient need. This may result in weekly 30-min sessions for 24 weeks or twice weekly hour-long sessions for 6 weeks. In practice, however, nearly all patients are seen in once-weekly 45- or 50-min sessions for 12 weeks. Mann admits having chosen the number 12 somewhat arbitrarily; however, his clinical experience indicates that somewhere between 10 and 14 sessions is a sufﬁ  cient number. Mann emphasizes the 
importance of a uniform number of sessions for evaluating the 
psychotherapeutic process among different therapists. In this way,

psychotherapeutic process among different therapists. In this way, 
the relationship between the patient’s presenting problems and psychotherapeutic technique can be more easily studied. Also, the provision of a speciﬁ  c number of sessions can be more easily 
accepted by the patient as a typical medical ‘prescription’ . Finally, the setting of a speciﬁ  c last session in the initial contract with the 
patient allows the therapy to have a clear beginning, middle, and 
end (see Table 6.3.4.1).
Mann indicates a number of exclusionary criteria: serious depres-
sion, acute psychosis, borderline personality organization, and the inability to identify a central issue. Mann sees Sifneos’ criteria as primarily excluding borderline patients. He does not agree with Sifneos’ emphasis on superior academic or work performance.
T o some extent, Mann initially minimized selection as a central

T o some extent, Mann initially minimized selection as a central 
issue for brief psychotherapy. Later, Mann expanded his selection criteria by emphasizing the importance of the patient’s ego strength as measured by prior work performance and past relationships.
(26)Patients who may have difﬁ  culty engaging and disengaging rapidly 
from treatment are excluded. This includes schizoid patients, certain obsessional patients, patients with strong dependency needs, some narcissistic patients, some depressive patients who will not be able to form a rapid therapeutic alliance, and some patients with psychosomatic disorders who do not tolerate loss well.
According to Mann, the selection of the central issue for the psy-

chotherapy is the critical event. It is the vehicle through which the patient is engaged in the work of therapy and on which a successful outcome depends. Mann looks for a central issue that is develop-mentally and adaptively relevant and has been recurrent over time. He describes this issue as the patient’s ‘present and chronically endured pain’ and characterizes it as preconscious. Mann has further described the central issue as including a particular image of the self.
(25) The central issue formulated in terms of time, affect, 
and an image of the self is the ‘paradigm of the transference’ expected to emerge in treatment. The therapist’s statement of the central issue is a clariﬁ  cation, which can be readily recognized, felt, and

held onto by the patient. Time-limited psychotherapy is intended to resolve this present and chronically endured pain and the patient’s ‘negative self-image’ . The therapist frames the central issue to the patient in terms of a general statement about feelings.
Mann and Goldman
(26) described in detail the phrasing of the 
central issue to the patient. It is the central issue that speciﬁ  es the

central issue to the patient. It is the central issue that speciﬁ  es the 
therapeutic contract and the goal of the therapy. In the case of a 41-year-old depressed woman who was preoccupied with her husband and children being even a minute late, Mann suggested the central issue: ‘Y ou’ve encountered extreme life situations and have managed them remarkably well ... yet you fear and have always feared that despite your best efforts you will lose everything’ . In a 31-year-old married man attempting to gain a college degree who was consumed with a fear of failing, Mann suggested the central issue: ‘Because there have been a number of sudden and very painful events in your life, things always seem uncertain, and you are excessively nervous because you do not expect anything to go along well. Things are always uncertain for you’ .
(26)
Mann uses the usual psychoanalytic psychotherapy techniques:

(26)
Mann uses the usual psychoanalytic psychotherapy techniques: 
defence analysis, transference interpretation, and genetic recon-struction. Transference is interpreted from within the central identiﬁ  ed conﬂ  ict area and in terms of the adaptive processes of the 
patient. However, Mann does not confront the patient. In general, his interventions are very close to the conscious material provided by the patient. Mann identiﬁ  es speciﬁ  c dynamic events that unfold 
during the 12 sessions. The opening sessions are understood as ﬁ lled with the unconscious magical expectation that past pains will 
now be resolved. During the initial phase, the therapist makes few comments and accepts the positive transference of the patient. Important aspects of the current problem, defence mechanisms, coping styles, and genetic roots of the central issue become clearer 
during this phase. In the middle four sessions, resistance is likely to

during this phase. In the middle four sessions, resistance is likely to 
appear, as well as the negative transference. The patient experiences 
the frustration that all of the wished for changes may not occur. 
In the ending phase of treatment, termination and the patient’s resistances to termination in the face of unresolved problems in other areas of life are prominent.
Mann sees the importance of confronting separation and 
termination issues as critical to the success of brief psychotherapy. Frequently, the patient unconsciously reveals an awareness that the mid-point of treatment has come. The patient experiences

1333
separation from the transference-invested therapist as a separation 
from an ambivalently experienced person from the past, without having achieved the fantasized magical resolution. The goal is to enable the patient to separate from the transference-invested thera-pist less ambivalently than he had done from this earlier important ﬁ gure. Consequently, both the resolution of the central issue and 
the unfolding of an attachment-separation process in the 12-ses-sion treatment contract are intimately related through the develop-ment and interpretation of the transference.
Davanloo: broad-focus short-term dynamic psychotherapy:
Davanloo writes about broad-focus short-term dynamic psychotherapy.
(27) His selection criteria include patients with an

(27) His selection criteria include patients with an 
Oedipal focus, those with a loss focus, and those with multiple foci. Davanloo is particularly interested in patients suffering from long-standing obsessional and phobic neuroses. His research data indicate that 30 to 35 per cent of the psychiatric outpatient popula-tion can beneﬁ  t from this mode of therapy. Most information 
about his technique is derived from the publication of cases, presentations, and brief descriptions of his research that accompany case presentations.
The initial evaluation is a speciﬁ  c focused interview in which 
the patient’s defences against ‘true’ feelings are gently but consis-tently confronted. Davanloo says that this is not a universal tech-nique for the initial interview and cautions on its use with patients with severe psychopathology. Selection is based on psychological

mindedness, the quality of the patient’s interpersonal relations, 
and, in particular, on the presence of at least one meaningful relationship in the patient’s past. The patient’s ability to tolerate and experience anxiety, guilt, and depression are important (Table 6.3.4.1). The patient must be motivated to complete the treatment process and to resolve neurotic problems. His or her ability to respond to interpretation is an important selection criterion. In particular, response to transference interpretations, which link the transference with the present and the past, is a critical feature in the assessment for broad-focus short-term dynamic psychother-apy. Davanloo ﬁ  nds no value in criteria based on severity and 
duration of illness. Finally, the presence of ﬂ  exibility in the ego’s 
defensive pattern and a lack of use of the primitive defences of pro-jection, splitting, and denial are important factors in selecting patients.

The technique Davanloo uses in therapy is a continuation of that 
used in the initial interview. The emotional experience of the patient in the transference is emphasized. The patient is ‘gently but relentlessly’ confronted about his defences against feelings in the transference relationship and in the past. All the usual tech-niques of psychoanalytic psychotherapy are employed: defence analysis, transference interpretations, and genetic reconstruction. Dreams and fantasy materials are also used. Transference interpre-tations tend to be made early. Because of the confrontive style, a strong therapeutic alliance is necessary. Patients frequently experience hostile, angry feelings towards the therapist because of being confronted. Davanloo actively pursues the patient’s defences against recognizing the anger and its transference elements.

Davanloo warns therapists that passive dependent and obsessional 
characters may develop a symbiotic transference relationship. This may be avoided through active confrontation and selection of patients. The active confrontation of defences and early transfer-ence interpretations tend to mobilize powerful affects and memo-ries early on in treatment.Davanloo recommends from 5 to 40 sessions, depending on the 
patient’s conﬂ  ict area (Oedipal versus multiple foci) and other 
selection criteria. In general, his treatments fall between 15 and 25 sessions. He does not recommend setting a speciﬁ  c termination 
date but rather makes clear to the patient that treatment will be short. Shorter time periods (5–15 sessions) are chosen for patients with a predominantly Oedipal focus, longer durations 
(20–40 sessions) for the more seriously ill group.
Comparison of psychodynamic, cognitive, and 
interpersonal brief psychotherapies
Interpersonal psychotherapy(28,29) and cognitive behavioural

Interpersonal psychotherapy(28,29) and cognitive behavioural 
psychotherapy(30) derive from the psychodynamic model and 
therefore share many common elements with brief psychodynamic psychotherapy but with distinct approaches and interventions. All three modalities, interpersonal psychotherapy, cognitivebehavioural therapy, and brief individual psychodynamic psychotherapy, are complex methods of treatment that must be custom-tailored to the individual patient. Brief by deﬁ  nition, they 
all lack the extended working through and application period of psychoanalysis and intensive (long-term) psychodynamic psycho-therapy. All demand a high degree of clinical judgement and considerable experience to acquire competency. The relationship between the therapist and patient and the establishment of a thera-peutic alliance are essential (Table 6.3.4.3).

Table 6.3.4.3  Comparison of the brief dynamic psychotherapy with 
cognitive psychotherapy and interpersonal psychotherapy
Brief dynamic 
psychotherapyCognitive 
psychotherapy Interpersonal 
Free association ++ + +
Directiveness + +++ ++Neutrality +++ +++ +++Time-limited +++ +++ +++Defence analysis +++ +++ +
Schema/distortions
Transference +++ + +++
Interpersonal
patterns
Behavioural 
interventions−− +++ +
Published manuals + ++ ++
Concurrent use 
of medication++ +++ +++
Empirical 
research indicates 
efﬁ  cacious treatments+ +++ +++
Training in 
long-term dynamic 
psychotherapy helpful+++ + +++6.3.4 brief individual psychodynamic psychotherapy

SECTION 6  treatment methods in psychiatry 1334
While sharing many similarities, it is ultimately in the concep-
tion of the problem, the goals, and therapeutic interventions that these treatments differ. It is unclear to what extent behavioural changes may be attributed to the similarities or differences between treatments. All psychotherapies, including brief individual psychodynamic psychotherapy, interpersonal psychotherapy, and cognitive behavioural therapy teach new skills-problem-solving skills directed at how to resolve interpersonal and emotional prob-lems when they arise. Differences among these psychotherapies in their interventions are more striking than the differences in their goals or the problem areas they identify for therapeutic work. In psychodynamic psychotherapy the structure of the session is deter-mined by the ﬂ  ow of the patient’s thoughts and their interaction

with the therapist’s interpretive comments. In contrast, cognitive and interpersonal psychotherapies use more directive, structured, and behavioural interventions. Whereas the brief individual psy-chodynamic psychotherapy like other psychodynamic psychother-apies relies on the patient to activate and practice new behaviours without direction. The therapist remains an empathic interpreter, a sharer of the patient’s experience and perspective. While in other therapies, especially cognitive, the therapist may direct, prescribe, enjoin, educate, or role play.
Practical problems in brief psychodynamic 
The choice of focus is perhaps the most important and the most 
difﬁ cult aspect of brief individual psychodynamic psychotherapy. 
It is helpful to identify several foci during the evaluation process, recognizing that there are inevitably several conﬂ  ict areas active at

It is helpful to identify several foci during the evaluation process, recognizing that there are inevitably several conﬂ  ict areas active at 
any one time in a patient’s life. Then the therapist can begin the process of thinking through what the treatment of each focus would entail (Table 6.3.4.4).
The therapist can begin to decide which focal conﬂ  ict will be 
more difﬁ  cult to reach in a brief period of time, which will threaten 
the therapeutic alliance more and therefore require a deeper work-ing relationship that may take more time, and which focus requires interpreting more primitive defences and therefore may be more complicated.
Choice of a particular focus can also create more family or exter-
nal disruption or support which can aid or disrupt the treatment.
Use of medication requires carefully explaining to the patient the

Use of medication requires carefully explaining to the patient the 
relationship of the medication to the psychotherapy. Often the medication treatment will continue beyond the psychotherapy. If repeated complicated medication alterations are needed or if 
serious side effects of the medication occur, the psychotherapy plan may have to be altered to allow time to understand them from the patient’s perspective.
New therapists are often concerned about setting the date of 
termination at the time of the evaluation, fearing that they may not be able to complete the work by the deadline. Supervision with an experienced colleague can be very helpful to assure conﬁ  dence and

avoid mistakes that may lengthen the treatment. Alternatively, the new therapist may feel too much relief in setting the termination date when treating a very dependent patient and therefore miss the intensity with which the patient is attached and experiencing the therapist as an important, needed, or feared ﬁ  gure from the past.
The management of missed sessions should be made clear at 
the beginning of treatment. Usually it is best not to ‘make up’ the 
sessions, but to keep to the termination date. If the therapist is concerned about this as a potential issue in the treatment, the therapist may wish to plan several additional sessions in the overall treatment to assure this can be discussed and understood thera-peutically. Of course if an emergency arises it is always appropriate to schedule appointments as needed for the health and safety of the patient.
The patient who ‘divulges’ new ‘secret’ information near the end

The patient who ‘divulges’ new ‘secret’ information near the end 
of the treatment is a challenge to all therapists. Understanding to what extent this represents narcissistic, or sociopathic issues, fear of the therapist or the treatment, or the emergence of hope for the future or a transference enactment will determine how to respond.
Brief individual psychodynamic psychotherapy is best learned in 
conjunction with the skills of longer term psychodynamic psycho-therapy. In the longer work, the therapist will be able to see more easily the possible conﬂ  ict areas and think about the sequencing of 
the treatment of these, i.e. which is closer to the patient’s awareness or which is more defended. In addition there is more time to correct errors and repair untoward events in the therapeutic relationship. The brief individual psychodynamic psychotherapist will have less time to correct mistakes and must more quickly identify conﬂ  ict areas and assess their relative importance and

potential for resolution through treatment.
Efﬁ cacy: research and evaluation
The brief psychodynamic treatments have a small empirical 
database. Much further research is needed.(31) In general, studies 
have supported the efﬁ  cacy of this treatment approach. However, 
methodological issues are prominent in most research in this area. The development of handbooks for treatment has gone far in improving research in the psychoanalytically oriented brief treatments.
(19, 32–34)
The effectiveness of psychotherapy in general, is not argued as in 
the past.(8, 35–37)  Brief psychodynamic psychotherapy has been 
shown to have an effect size similar to many other medical treatme nts. 
Short-term psychodynamic psychotherapy has shown modest to moderate, often sustained gains for a variety of patients.
(38)

(38)
However, the question of which psychotherapy is suitable for which patient and by which therapist is still unclear. The cost-effectiveness of psychotherapeutic treatment remains hotly debated and is a focus of substantial research.
(9, 39, 40) Individual psychotherapy has 
been shown to result in fewer days of hospital stay for patients on medical or surgical services of a general hospital. In health clinics Table 6.3.4.4  Identifying and selecting the focal conﬂ  ict in brief 
dynamic psychotherapy
Identifying the focal conﬂ  ict
Explore
 Precipitant of symptoms
 Early life traumas Repetitive patterns of behaviour Listen for inhibitions/avoidance Watch for conﬂ  icts about success as well as loss/failure
Selection among several foci

Precipitant of symptoms
 Choose the focus that is presently active Use trial interpretation to identify active focus Select focus related to only one transference ﬁ  gure

1335
or health maintenance organizations, brief psychotherapy decreases 
the number of visits to primary health care providers, reduces the number of laboratory and radiographic studies, decreases the number of prescriptions given, and, overall, reduces direct health care costs. Recently summaries of the cost-offset effects of outpa-tient mental health treatment, the majority of which were short-term are hopeful but not unambiguous. One study found outpatient psychotherapy resulted in a 33 per cent average reduction in medi-cal care utilization. Furthermore, these reductions occurred mostly in the more expensive, inpatient medical services. In another study, 72 patients with signiﬁ  cant emotional problems and treated only 
by internists in a general medical clinic were compared with 62 patients who, in addition to being treated by internists for medical problems, received 10 weekly psychotherapy visits. Both groups had approximately an equal de gree of emot ional distur bance.

At 4-month and 1-year follow-ups, the brief psychotherapy group reported signiﬁ  cantly more global improvement than the non-
psychotherapy group. Also, more patients in the brief psychotherapy group became employed at 1-year follow-up than in the non-psychotherapy group. This study suggests speciﬁ  c beneﬁ  cial effects 
of brief psychotherapy when used in a medical setting by skilled psychotherapists. Combining psychotherapy with antidepressant medication has also been shown to give the best outcome at 1 year when compared to either treatment alone. Whether a therapist keeps to a consistent frame of reference in the treatment may also be a predictor of success if brief individual psychodynamic psycho-therapy, regardless of what that perspective is.
(41)
Malan’s ﬁ  nding of the importance of making the transference-
parent link for the successful outcome of treatment is signiﬁ  cant 
and requires further exploration.(2) One reanalysis of Malan’s data

and requires further exploration.(2) One reanalysis of Malan’s data 
conﬁ  rmed his ﬁ  nding and one did not.(42) In addition, one replica-
tion of this ﬁ  nding has been published.(43) Importantly, more 
recently, the overuse of transference interpretations has been shown to lead to poorer outcome. The therapeutic alliance, particularly when measured from the patient’s perspective, has a consistent although modest contribution to outcome.
(9, 44) It has been shown 
that independent of the type of treatment and early clinical improvement, the therapeutic relationship contributes directly to the positive therapeutic outcome.
(45)
The quality of the therapeutic interaction and the handling 
of the transference and countertransference appears to be critical to success or failure in brief individual psychodynamic psychotherapy.
(34) Patients treated by therapists who have not been

(34) Patients treated by therapists who have not been 
professionally trained, may, on average, be as improved as patients treated by professional brief dynamic therapists. However, such non-experienced therapists run out of relevant material and are unwilling to continue to treat patients over an extended period of time.
(46) One of the important tasks of training in psychotherapy 
may be the development of the ability to ‘endure’ with the patient and, over time, with numbers of patients. T echnical training and a theoretical framework may allow the therapist to maintain a sense of competence, direction, and interest in the work which the non-professional therapist cannot.
Interpersonal psychotherapy and cognitive-behavioural therapy

Interpersonal psychotherapy and cognitive-behavioural therapy 
have been much more extensively studied than dynamic psycho-therapy, particularly in combination with medications. Recently, telephone psychotherapy with cognitive behavioural therapy in primary care settings when initiating antidepressant medication has been shown to improve clinical outcome.
(47, 48) T o the extent that these treatments share techniques and outcomes, similar 
results might be expected with brief dynamic psychotherapy; how-ever, this still needs to be shown. Focal directive psychotherapies generally appear to be more effective than traditional unstructured 
psychodynamic psychotherapy for a number of types of patients, but a delineation of which psychotherapy for which patient over

psychodynamic psychotherapy for a number of types of patients, but a delineation of which psychotherapy for which patient over 
what time and with which medication remains to be demonstrated. Good clinical sense dictates combined treatments with matching the patient’s cognitive and affective style with treatment type and making medication compliance a focus of any psychotherapy. Additionally, further research of brief psychodynamic psychother-apies in speciﬁ  c psychiatric disorders as well as across the life span 
are needed.
(49, 50)

(49, 50)
Brief dynamic psychotherapy is an important treatment for numer-ous disorders, primarily the adjustment, anxiety, and mood disorders. Both alone and in combination with medication brief dynamic psychotherapy is an effective part of the treatment armamentarium. Clinicians should be trained in the brief as well as the longer term treatments and their use as brief, intermittent, and mainte-nance treatments. Skill in the longer term psychotherapies is important to developing skill in the brief dynamic psychotherapy where the needs for rapid establishment of the therapeutic alliance and the accurate assessment of transference and defence patterns are important.
Empirical studies comparing well-defined brief dynamic 
psychotherapy with cognitive and interpersonal psychotherapies are limited. Future research must address which form of brief 
psychotherapy may be most helpful for which patient. An individ-

ual’s preferred learning path-what he or she may see and observe most easily such as thoughts or feelings or interpersonal relations-may be an important variable in determining which brief psycho-therapy for which patient. State, trait, and contextual variables will inﬂ  uence this learning modality. The process of change in 
brief individual psychodynamic psychotherapy, a process of alter-ing neuronal organization through verbal means, is inﬂ  uenced 
by the patient’s diagnosis, medications, past history, cognitive style, developmental stage, and affective availability, as well as the doctor–patient match.
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6.3.5 Psychoanalysis and 
other long-term dynamic psychotherapies
Basic assumptions
The term psychodynamic psychotherapy has no speciﬁ  c referent. 
It denotes a very heterogeneous range of psychological treatment approaches which arguably have in common an intellectual heritage of psychoanalytic theory. Psychoanalytic theory itself is no longer based on a unitary body of ideas
(1) but a number of ideas appear to 
be core to most psychodynamic approaches. These notions are:
(a) A shared notion of psychological causation, that mental disor-
ders can be meaningfully conceived of as speciﬁ  c organizations

ders can be meaningfully conceived of as speciﬁ  c organizations 
of an individual’s conscious or unconscious beliefs, thoughts, and feelings.
(b) Psychological causation extends to the non-conscious part of 
the mind, and to understand conscious experiences, we need to refer to other mental states of which the individual is unaware.
(c) The mind is organized to avoid unpleasure arising out of 
conﬂ  ict
(2) in order to maximize a subjective sense of safety.(3)
(d) Defensive strategies are a class of mental operations that seem 
to distort mental states to reduce their capacity to generate anxiety, distress, or displeasure. Individual differences in the predisposition to speciﬁ  c strategies have often been used as a 
method for categorizing individuals or mental disorders.
(4, 5)
(e) Varying assumptions are made concerning normal and abnormal

(4, 5)
child and adolescent development but therapists are invariably oriented to the developmental aspects of their patients’ pre-senting problems.
(6)
(f) Relationship representations linked with childhood experience 
are assumed to inﬂ  uence interpersonal social expectations 
including the transference relationship with the therapist(7)
and to shape the representations of the self.(8–11)
(g) These relationship representations inevitably re-emerge in the 
course of psychodynamic treatments.(12)
Brief overview of theories

Psychoanalytic theory has evolved from the work of Freud follow-ing two broadly separate paths which converged over the past 25 years only to separate again. In the United States followers of the Vienna school in the 1950s and 1960s evolved a systematic psychol-ogy of the ego, a conﬂ  ict-oriented complex psychological model of the mind and its disturbances.
(13) In Europe, only Anna Freud 
and her followers in London pursued this tradition of psychoana-lytic thought.
(14) Based on the Berlin school of Karl Abraham, 
Melanie Klein and her followers established a distinct approach 
focusing on the understanding of disturbance rooted in infantile destructiveness and sadism.
(15) Some psychoanalysts, inﬂ  uenced

(15) Some psychoanalysts, inﬂ  uenced 
by Klein and the idea of the pathogenic nature of the experiences of infancy, gradually discarded the mechanistic psychology of drives and psychology of internal structures in favour of theories of intra-psychic interpersonal relationships (object-relations theory).
(16)
As these schools developed in the United Kingdom, their inﬂ  u-
ence travelled across the Atlantic. First, Kohut, strongly inﬂ  uenced 
by Winnicott (albeit without explicit acknowledgement), evolved a psychoanalytic psychology of the self.
(17) Shortly after, Kernberg 
arrived at an imaginative integration of ego-psychological and Kleinian ideas.
(18) In the meantime, in the United Kingdom, the

(18) In the meantime, in the United Kingdom, the 
Kleinian movement rapidly progressed in their understanding of psychoanalytic clinical experience, moving beyond Klein’s original work and integrating some of the key features of the Anna Freudian and the British object-relations traditions.
(19) In the United States, 
disillusionment with the false certainty provided by ego-psychology became intense throughout the late 1970s and early 1980s and a radical change in psychoanalytic thinking took place with the emergence of the interpersonal relational perspective, which is in part rooted in the work of Harry Stack Sullivan.
(20,21)  The relational 
psychoanalysis of the 1980s and 1990s consolidated several lines of thought initiated by justiﬁ  ed critiques of traditional analytic 
theory
(22); including feminism, the hermeneutic-constructivist

theory
(22); including feminism, the hermeneutic-constructivist 
critique of the analyst’s authority, infancy research, and, closely related to this, the intersubjectivist-phenomenological philosophy of mind—as well as a general political movement to improve and democratize access to analytic ideas and training.
(23)
There are many other new psychoanalytic theoretical approaches, 
bringing the ﬁ  eld increasingly close to total fragmentation.(24) This is 
because the emergence of new approaches in no way signals the demise of any previous orientations, most of which continue to enjoy considerable popularity among speciﬁ  c groups of psychoanalysts.
Psychoanalytic therapy as treatment
The history of psychoanalysis as a therapeutic approach is rather

The history of psychoanalysis as a therapeutic approach is rather 
different. Broadly speaking, it may be argued that psychoanalysis and other long-term psychodynamic therapies are predominantly verbal, interpretive, insight-oriented approaches which aim to modify or re-structure maladaptive relationship representations. It is implicitly assumed that genetic and early environmental factors give rise to partial, unintegrated, and generally troublesome relationship representations (e.g. a helpless ‘infant’ requiring total care from an adult, a self with exaggerated sense of power, and entitlement requiring constant conﬁ  rmation from outside) that lie 
at the root of psychological disturbance. It is believed that the integration of these partial representations into more complex schemata, primarily but not exclusively through the use of insight, leads to improved internal and social adjustment.

Psychoanalysis is the most intensive form of these long-term 
therapies. The analysand attends treatment three or more times a week over a period of years. The use of the couch and the instruc-tion to the analysand to free associate have been considered hallmarks. The distinction between psychoanalysis and other forms of psychotherapy is normally made in terms of the frequency of 6.3.5 psychoanalysis and other long-term dynamic psychotherapies

SECTION 6  treatment methods in psychiatry 1338
sessions rather than in terms of the therapeutic stance of the ana-
lyst. It is difﬁ  cult to avoid the conclusion that in the absence of 
plausible, theoretically based criteria for what is or is not psycho-analytic, against the background of an overwhelming diversity of theoretical frameworks, psychoanalysts have attempted to ﬁ  nd 
common ground in readily identiﬁ  able treatment parameters. This 
problem arises as a consequence of an extremely loose relationship between psychoanalytic theory and clinical practice.
(24) It is an 
indisputable fact that, whereas theory has evolved extremely rap-idly in the last half of the twentieth century and continues to change, psychoanalytic practice has, until recently, changed sur-prisingly little and continues to provide the core of the psychoana-lytic identity. On the other hand, the follow-along study by Sandell et al.
(25) found that psychoanalysis and psychoanalytic psychother-

apy were ‘separate things’ . When psychotherapy was performed using mainly psychoanalytic techniques, it was less effective than psychotherapy performed with modiﬁ  ed and adjusted techniques 
(that is, not performed as an ‘as-if analysis’). The ﬁ  ndings from the 
Stockholm study suggest that psychoanalysis and psychoanalytic psycho therapy may be separate endeavours, although how exactly they differ is far from clear.
In this chapter we will not consider the theoretical richness of 
this ﬁ  eld but instead will focus on the clinical constructs which run 
across the diverse intellectual approaches. The intersection of the two is perhaps clearest in one area which we shall consider in some detail—namely, the therapeutic action of long-term psychoanalytically oriented psychotherapeutic treatment.
Historical development of the psychoanalytic 
approach to treatment

As is well known, Freud’s discovery of the talking cure(26) was really 
that of an intelligent patient (Anna O) and her physician (Breuer). The patient reported that certain symptoms disappeared when she succeeded in linking up fragments of what she said and did in an altered state of consciousness (which we might now call dis-sociative) with forgotten impressions from her waking life. Breuer’s remarkable contribution was that he had faith in the reality of the memories which emerged and did not dismiss the patient’s associations as products of a deranged mind. The patient’s response to treatment was probably less complete than Breuer and the young Freud had hoped
(27) but the ‘treatment’ deﬁ  ned the basic 
elements of the ‘cathartic’ method-linking memory of trauma (the circumstances of her experience of her father’s death) to her many symptoms.

At ﬁ rst Freud rigorously pursued the traumatogenic origins of 
neuroses. Later, when confronted by evidently incorrect statements, he modiﬁ  ed his theory, assuming consistency between recollection 
and childhood psychic reality rather than physical reality.
(28) The 
issue of accuracy of memories of childhood sexual trauma remains controversial, although its relevance to psychoanalytic technique is at best tangential.
(29) Freud’s technique, however, was dramatically 
modiﬁ  ed by his discoveries. The intense emotional relationship

modiﬁ  ed by his discoveries. The intense emotional relationship 
between patient and physician, which had its roots in catharsis following hypnotic suggestion, had gradually subsided into what was principally an intellectual exercise to reconstruct the repressed causes of psychiatric disturbance from the fragments of material derived from the patient’s associations. It was a highly mechanistic 
approach reminiscent of a complex crossword puzzle. In the light of therapeutic failures, however, Freud once more restored the emotional charge into the patient–physician relationship.
(30)
However, in place of hypnosis and suggestion, he used the patient’s

(30)
However, in place of hypnosis and suggestion, he used the patient’s 
emotion, signs of transference of affect and affective resistance which were manifest in the analytic relationship. Instead of seeing the patient’s intense emotional reaction to the therapist as an interference, Freud came to recognize the importance of transfer-ence as a representation of earlier relationship experiences which could make the reconstruction of those experiences in analysis highly meaningful to that individual.
(31)
Freud’s early clinical work evidently lacked some of the rigour 
which came to characterize classical psychoanalysis.(32) His occa-
sional encouragement to his patients to join him on holiday might now be considered a boundary violation.
(33) What is perhaps less 
well known is that Freud remained somewhat sceptical about the effectiveness of psychoanalysis as a method of treatment.
(34)

(34)
Indeed, autobiographies of some of his patients testify to his great ﬂ exibility as a clinician and use of non-psychoanalytic techniques, 
including behavioural methods.
(35) Nor was Freud the only clini cian 
to use psychoanalytic ideas ﬂ  exibly. The Hungarian analyst Sandór 
Ferenczi should be credited with the discovery of the treatment of phobic disorders by relaxation and exposure
(36) although many 
of his well-intentioned actions were criticized by contemporaries and more recently on arguable ethical grounds.
(37)
The technique of psychoanalysis after Freud’s death came to be 
codiﬁ  ed. Those (such as Alexander and French and Freda Fromm-
Reichmann) who attempted to revive or retain Freud’s original clinical flexibility were subjected to powerful intellectual rebuttals.

(38) In reality, psychoanalysts probably continued to vary 
in the extent to which they observed the ideals of therapeutic neutrality, abstinence, and a primarily interpretive stance, but these deviations could no longer be exposed to public scrutiny for fear of colleagues’ forceful condemnation. Personal accounts of analyses with leading ﬁ  gures yield fascinating insights into variations in 
technique, principally in terms of the extent to which the analyst made use of a personal relationship.
(39) There has been an ongoing

(39) There has been an ongoing 
dialectic throughout the history of psychodynamic approaches between those who emphasize interpretation and insight and those who stress the unique emotional relationship between patient and therapist as the primary vehicle of change. The controversy dates back to disputes concerning the work of Ferenczi and Rank
(40) but 
re-emerged with the ﬁ  rst papers of Balint and Winnicott in London 
opposing a Freudian and Kleinian tradition, and somewhat later in the United States with Kohut and more subtly Loewald opposing classical ego psychology.
In the last two decades, the pluralistic approach of modern 
psychoanalysis has brought out into the open many important 
dimensions along which psychoanalysts’ techniques may vary. 
In particular, the recent trend to consider analyst and patient as equal partners engaged in a mutual exploration of meaning
(41)

(41)
directly challenged many of the classical constructs. The emphasis on the mutual influence of infant and caregiver shaped the emerging relational model of therapy as a two-person process in which there was little room for a detached analyst with pretensions of ‘objectivity’ . Drawing on the assumption that humans are predisposed towards two-person co-constructed systems that provide a context for psychic change, the quality of engagement

1339
between therapist and patient became the core of therapeutic 
action. What changes the mind is not the insights gained but learn-ing from the interactional experience of being with another person. Neither the analyst nor the patient can be considered as forging meaning; rather, meaning is co-constructed.
Technique—principal features
Neutrality and abstinence
Based in the classical framework of libidinal theory, Freud made an explicit injunction against the analyst giving in to the temptation of gratifying the patient’s sexual desire.
(42) Obviously, this is pri-
marily an ethical issue. However, within the psychoanalytic context it also justiﬁ  es the analyst’s stance of resisting the patient’s curiosity 
or using the therapeutic relationship in any way that consciously or unconsciously could be seen as motivated by the need to gratify their own hidden desires. Within this classical frame of reference, the patient must also agree to forgo signiﬁ  cant life changes where

these could be seen as relevant to current psychotherapeutic work. In practice, such abstinence on the part of the patient is rare. Y et long-term psychodynamic treatment may founder if the emo-tional experiences of the therapy are obscured by the upheavals of signiﬁ  cant life events.
The primary function of abstinence is to ensure the neutrality of 
the therapist. The analyst assumes an attitude of open curiosity, 
empathy, and concern in relation to the patient. The therapist

empathy, and concern in relation to the patient. The therapist 
resists the temptation to direct the patient’s associations and remains neutral irrespective of the subject matter of the patient’s experiences or fantasies. While it is easy to take this issue too lightly, (and it is perhaps this aspect of the psychoanalyst’s therapeutic stance which makes them most vulnerable to ridicule), it is proba-bly genuinely critical for the therapist to retain emotional distance from the patient to a degree which enables the latter to bring fanta-sies and fears of which they feel uncertain. Nevertheless, neutrality at its worst denies the possibility of sensitivity; recent literature on the process and outcome of psychotherapy makes it clear that the therapist’s genuine concern for the patient must become manifest

if signiﬁ  cant therapeutic change is to be achieved.
(43) The quality 
of the alliance is one of the better predictors of outcome(44) and 
alliance is impacted by the patient’s attachment style and quality of object-relations.
(45)
Mechanisms of defence
The term ‘psychic defences’ may risk reiﬁ  cation and anthropomor-
phism (precisely who is defending whom against what?) yet the existence of self-serving distortions of mental states relative to an external or internal reality is generally accepted, and frequently demonstrated experimentally.
(46–48)  Within classical psychoana-
lytical theory and its modern equivalent (ego psychology), intra-psychic conﬂ  ict is seen as the core of mental functioning.
(49)
Here defences are seen as adaptations to reduce conﬂ  ict. Within 
many object-relations theories, defences are seen as helpful to the individual to maintain an authentic or ‘true’ self-representation or a nuclear self.
(17) Models of representations of relationships are

(17) Models of representations of relationships are 
of course often defensive. Traumatic experiences may give rise to omnipotent internal working models to address a feeling of helplessness. Within attachment theory, defences are construed 
as assisting in the maintenance of desirable relationships.
(50)
The Klein–Bion model makes limited use of the notion of defence mechanisms but uses the term in the context of more complex 
hypothetical structures called defensive organizations.(19) The term 
underscores the relative inﬂ  exibility of some defensive structures, 
which are thus best conceived of as personality types. For example, narcissistic personality disorder combines idealization and destruc-tiveness; genuine love and truth are devalued. Such a personality type may have been protective to the individual at an earlier devel-opmental stage, and has now acquired a stability or autonomy which must be rooted in the emotional gratiﬁ  cation which such a

self-limiting form of adaptation provides.
(51)
Irrespective of the theoretical frame of reference, from a thera-
peutic viewpoint clinicians tend to differentiate between so-called primitive and mature defences based on the cognitive complexity entailed in their functioning.
(52) In clinical work, primitive defences 
are often noted together in the same individual. For example, individuals loosely considered ‘borderline’ tend to idealize and then derogate the therapist. Thus they maintain their self-esteem by using splitting (clear separation of good from bad self-perception) and then projection. Projective identiﬁ  cation
(53) is an elaboration

(53) is an elaboration 
of the process of projection. An individual may ascribe an undesir-able mental state to the other through projection but when the other can be unconsciously forced to accept the projection and experience its impact, the defence becomes far more powerful and stable. The analyst’s experiencing of a fragment of the patient’s self-state, has in recent years been considered an essential part of therapeutic understanding.
(54)
Whether in fantasy or in actualized form, through projective 
identiﬁ  cation the patient can experience a primitive mode of con-
trol over the therapist. Bion argued that when the self is experi-enced as being within another person (the therapist) the patient frequently attempts to exert total control over the recipient of the projection as part of an attempt to control split-off aspects of the self. Bion
(55) also argued that not all such externalizations were of

(55) also argued that not all such externalizations were of 
‘bad’ parts of the self. Desirable aspects of the self may also be projected, and thus projective identiﬁ  cation can be seen as a primi-
tive mode of communication in infancy. There are other aspects of projective identiﬁ  cation which we commonly encounter clinically. 
These include the acquisition of the object’s attributes in fantasy, the protection of a valued aspect of the self from internal persecu-tion through its evacuation into the object, and the avoidance or denial of separateness. It is thus a fundamental aspect of inter-personal relationship focused on unconscious fantasy and its appreciation is critical for the adequate practice of long-term psychotherapy.
(56)
Classiﬁ  cations of defences have been frequently attempted(52, 57–61)
and often as a method for categorizing individuals or mental 
disorders.(4, 5) An attachment theory-based classiﬁ  cation rooted in

disorders.(4, 5) An attachment theory-based classiﬁ  cation rooted in 
the notion of habitual deactivation or hyperactivation of the attachment system (‘attachment style’) has achieved general acceptance.
(62, 63) Deactivating (‘avoidant’ or ‘dismissing’) strate-
gies include suppression of ideas related to painful attachment experiences, repressing painful memories, minimizing stress and distress, segregated mental systems that result in the defensive exclusion of distressing material from the stream of conscious-ness.
(64, 65)  Ingenious experimental studies have shown that indi-
viduals who habitually use avoidant defences are more efﬁ  cient, 
when instructed, at suppressing conscious thoughts and associated feelings about a romantic partner leaving them for someone else
(66)
and are more likely to attribute their own unwanted traits to others 6.3.5 psychoanalysis and other long-term dynamic psychotherapies

SECTION 6  treatment methods in psychiatry 1340
(projection) which serves to both increase self-other differentiation 
and enhance self-worth.(67) In a further, remarkable study the same 
group of researchers demonstrated that the above advantages of the suppression strategy of those using avoidant defence fall away in the laboratory situation if a cognitive load is placed on the participant which then leaves them literally defenceless so that they experience a heightened rebound of previously suppressed thought about painful separation.
(68) The cognitive and socio-cognitive

(68) The cognitive and socio-cognitive 
strategies associated with reducing anxiety or displeasure and enhancing safety, which both the attachment theory and psycho-analytic literatures tend to refer to as defences, are perhaps better thought of not as independent classes of mental activity or psycho-logical entities but as a pervasive dynamic aspect of complex cogni-tion interfacing with attachment relationships and emotional experience. Some mechanisms of defence are thought to be more characteristic of the less severe psychological disorders (e.g. depres-sion, anxiety, obsessive–compulsive disorders, etc.). It is beyond the scope of this chapter to consider the various defence mechanisms in detail.
Modes of therapeutic action
The primary mode of the therapeutic action of psychoanalytic psychotherapy is generally considered to be insight.
(69) Insight may 
be deﬁ  ned as the conscious recognition of the role of unconscious

be deﬁ  ned as the conscious recognition of the role of unconscious 
factors on current experience and behaviour. Unconscious factors encompass unconscious feelings, experiences, and fantasies. The psychodynamic model has been seen as a model of the mind that emphasizes repudiated wishes and ideas which have been warded off, defensively excluded from conscious experience. In our view this is a narrow and somewhat misleading way to deﬁ  ne the 
therapeutic mechanism for approaches that are considered as psychodynamic. The psychodynamic approach is better seen as a stance taken to human subjectivity that is comprehensive, and aimed at understanding all aspects of the individual’s relationship with her or his environment, external, and internal. Freud’s great discovery (‘where id was, there ego shall be’ , Freud
(70) p. 80), often

(70) p. 80), often 
misinterpreted, points to the power of the conscious mind radically to alter its position with respect to aspects of its own functions, including the capacity to end its own existence through killing the body. Psychodynamic, in our view, refers to this extraordinary potential for dynamic self-alteration and self-correction—seemingly totally outside the reach of non-human species. Engaging with this potential to bring change through understanding, is the science and the art of the psychodynamic clinician.
Conscious insight is more than mere intellectual knowledge
(71, 72)
or descriptive insights. Prototypically, psychodynamic therapy achieves demonstrated or ostensive insights which represent a more direct form of knowing, implying emotional contact with an event one has experienced previously.  Working with w hat is no n-con scious

is at the heart of the dynamic approach to bringing about psycho-logical change because of the force that awareness of unconscious expectations can bring to the interpretation of behaviour. Although specific formulations of the effect of insight depend on the theoretical framework in which explanations are couched, there is general agreement that insight has its therapeutic effect by in some way integrating mental structures.
(72) Kleinian analysts(73) tend to 
see the healing of defensively created splits in the patient’s repre-sentation of self and others as crucial. Split or part-objects may also be understood as isolated representations of intentional beings whose motivation is insufﬁ  ciently well understood for these to be 
seen as coherent beings.
(74) In this case insight could be seen as a 
development of the capacity to understand internal and external objects in mental state terms, thus lending them coherence and consistency.
(75) The same phenomenon may be described as an

(75) The same phenomenon may be described as an 
increasing willingness on the part of the patient to see the interper-sonal world from a third person’s perspective.
(76)
A simple demonstration to the patient of such an integrated 
picture of self or others is not thought to be sufﬁ  cient.(31) The 
patient needs to ‘work through’ a newly arrived integration. Working through is a process of both unlearning and learning: actively discarding prior misconceptions and assimilating learning to work with new constructions. The technique of working through is not well described in the literature, yet it represents the critical advantage of long-term over short-term therapy.
(77) Working

(77) Working 
through should be systematic and much of the advantage of long-term treatment may be lost if the therapist does not follow through insights in a relatively consistent and coherent manner.
In contrast to the emphasis on insight and working through are 
those clinicians who, as we have seen, emphasize the ‘relationship aspect’ of psychoanalytic therapy (Balint, Winnicott, Loewald, Mitchell, and many others). This aspect of psychoanalytic therapy was perhaps most eloquently described by Loewald when he wrote about the process of change as: ‘set in motion, not simply by the technical skill of the analyst but by the fact that the analyst makes himself available for the development of a new ‘object-relationship’ between the patient and the analyst . . . ’(Loewald, 1960, pp. 224–5).
(78) Sandler and Dreher(79) have recently observed

(78) Sandler and Dreher(79) have recently observed 
‘while insight is aimed for it is no longer regarded as an absolutely necessary requirement without which the analysis cannot proceed’ . There is general agreement that the past polarization of interpreta-tion and insight on the one hand, and bringing about change by presenting the patient with a new relationship on the other, was unhelpful. It seems that patients require both, and both may be required for either to be effective.
(80)
Controversy remains even if all accept that neutrality is an 
impossible and undesirable ﬁ  ction and that patient and therapist 
affect each other in myriad mutually inﬂ  uencing ways. Projective 
identiﬁ  cation is seen as occurring in a bidirectional interpersonal 
ﬁ eld between analyst and patient—a model clearly adapted from 
Kleinian approaches to infant-caregiver interaction.(23) If we take

Kleinian approaches to infant-caregiver interaction.(23) If we take 
this perspective seriously, we have to concede that all analytic inter-ventions change the situations into which they are introduced, and their content and style always reﬂ  ect the analyst’s counter-
transference/response to the treatment situation.
(81) Relational 
psychoanalysis advocates making the interactional inﬂ  uence of 
analyst upon patient explicit. As Levenson(82)(p. 9) put it, the key 
therapeutic question is not ‘what does this mean?’ but rather ‘what is going on around here?’ The therapist will ‘act’ on the patient; this 
is not a therapeutic disaster but rather a potentially progressive and 
certainly inevitable part of the process.
It has been suggested that change in analysis will always be 
individualized according to the characteristics of the patient or the analyst.
(83) For example, Blatt(84) suggested that patients who were

(83) For example, Blatt(84) suggested that patients who were 
‘introjective’ (preoccupied with establishing and maintaining a viable self-concept rather than establishing intimacy) were more responsive to interpretation and insight. By contrast, anaclitic patients (more concerned with issues of relatedness than of self-development) were more likely to beneﬁ  t from the quality of

1341
the therapeutic relationship than from interpretation. Taking a 
second look at large-scale outcome investigations Blatt found strong evidence for the oft made but rarely demonstrated claim of patient personality—therapeutic technique ﬁ  t.
(85)
Indications and contraindications and 
selection procedures
Medical treatments normally have indications and contraindications. 
In psychodynamic treatment the term ‘suitability’ indicates a looser notion of the appropriateness of the approach.
(86) Nevertheless, 
based primarily on clinical experience, some writers have arrived at specific criteria for long-term psychodynamic therapy.
(87)
Some authors have also suggested relatively systematic methods of assessment yielding both diagnostic and prognostic informa-tion.
(88) The majority of psychodynamic clinicians, however, rely 
on clinical judgements based on interpersonal aspects of their ﬁ  rst 
meeting with the patient.(71) The three areas of assessment are

meeting with the patient.(71) The three areas of assessment are 
personal history, the content of the interview, and the style of the presentation.
A history of one good relationship has been traditionally 
regarded as a good indicator.
(89) By contrast, a history of psychotic 
breakdown, severe obsessional states, somatization, and lack of frustration tolerance are generally considered contraindications. For example, a challenging set of re-analyses of the Treatment of Depression Collaborative Research Program found that the trait of perfectionism was associated with poor outcome, and could under-mine the therapeutic alliance and the patient’s satisfaction with social relations, limiting their improvement in the course of brief treatment for depression.
(90)
Empirical literature, to the meagre extent that this is available,

(90)
Empirical literature, to the meagre extent that this is available, 
suggests that many of the presuppositions about suitability are unfounded. It was, for example, assumed that patients who mani-fested more serious mental illness, especially disturbances in reality testing, were unsuitable for psychoanalysis; however, a recent study showed that some patients with serious disturbances in reality test-ing were able to beneﬁ  t from psychoanalysis when their analysts 
were able to tolerate and analyse this level of psychopathology.
(91)
What does seem to be consistent is that severity of symptoms, as well as functional levels in work and relationships, are correlated with the outcome of psychotherapy
(92)—although no single patient 
variable is a strong predictor of outcome. This is why the effects of psychotherapy, good and bad, can sometimes be surprising.
Predicition based on the content of assessment interviews is

Predicition based on the content of assessment interviews is 
hard. In general, the presence of some kind of ‘mutuality’ between therapist and patient is a positive indicator. Some clinicians offer ‘trial interpretations’ which summarize their initial impressions, and a positive thoughtful response to these is regarded a good indication. The capacity to respond emotionally within the assess-
ment session is a further indicator.
(93) Motivation for treatment is 
harder to ascertain. Most patients express enthusiasm for the treatment, which falls away once they are asked to confront unpleas-ant or unﬂ  attering parts of themselves.
More recently, psychodynamic therapists have given increasing 
consideration to the style of the patient’s discourse during assess-ment rather than its content. Holmes,
(94) for example, attempts to

(94) for example, attempts to 
identify whether patients’ narrative styles are avoidant (sparse and dismissing of interpersonal issues) or enmeshed and entangled (excessive current anger about past hurts and insults). The ﬁ  ndings of one study indicate that, in a severely personality disordered 
population at least, the avoidant type of patient has a better prog-nosis in psychodynamic therapy.
(95) A further relevant capacity is 
reﬂ ective function or mentalization, often reﬂ  ected in narrative; 
this has been variously described as seeing oneself from the 
outside,(96) reﬂ ecting on one’s inner world(87) or having ﬂ  uidity of 
thought.(97)
(a) Establishing parameters

Most psychodynamic therapists, explicitly or implicitly, convey objectives and expectations to their patients. The details of this agreement normally include arrangements for a time and a place as well as the length and frequency of sessions. Usually a tentative idea is offered as to the likely duration of therapy: ‘It is likely to take years rather than months.’ Most therapists also describe the expected behaviour of the patient and the therapist: ‘I would like you to be as open and honest with me as possible and say absolutely everything that comes into your mind. This is the fundamental rule.’ In fact it is very likely, in view of the variety of such agreements that tend to be made, that its emotional context is more relevant than the speciﬁ  c items agreed upon. Such a ‘contract’ implies recogni-

tion by both patient and therapist that the process of therapy needs protecting and that it is important enough to require a sacriﬁ  ce 
from both parties.
In the treatment of severe personality disorders, contracts may 
have an additional important function—that of protecting the therapy from incessant enactments, self-harming, parasuicidal gestures, and so on. In Kernberg’s approach to the treatment of borderline patients, the patient formally undertakes not to seek the therapist’s help outside of ofﬁ  ce hours, not to engage in acts of 
violence and to deal with self-destructive acts through normal medical channels.
(98) Whilst such agreements are commonly made 
in long-term therapy, it is by no means clear that they are either essential or useful. For example, in an alternative form of psychody-namic therapy, Mentalization-Based Treatment (MBT), contracts are not recommended.
(99)
(b) Formulation of patients’ problems

(99)
An important part of initiating any psychosocial treatment is arriving at least at a preliminary formulation of the patient’s problems. In the case of psychodynamic therapies this represents a special challenge because of the diversity of the possible theories to draw on. In principle, psychodynamic formulations would identify key unconscious conﬂ  icts, central maladaptive defences, 
unhelpful unconscious fantasies and expectations, deficits in personal development, and so on. The complexity of such formula-tions is such that agreements are hard to arrive at even when clini-cians follow similar orientations. In the absence of a generally accepted format for formulating the patient’s problems, a list of key parameters for the level of maturity of personality organization may be offered:
(a) the maturity of relationship representations (three or more 
persons versus just a self-other dimension)

(b) the maturity of psychic defences (primarily based on projec-
tive versus internalizing processes)6.3.5 psychoanalysis and other long-term dynamic psychotherapies

SECTION 6  treatment methods in psychiatry 1342
(c) the extent of whole as opposed to part object-relations (e.g. 
whether a person is represented as performing more than a single function for the patient)
(d) the general mutuality of the relationship patterns described; 
the quality of attachment to others.
It should be noted that psychodynamic formulations tend to 
change as treatment progresses. Indeed, Winnicott described psychoanalysis as ‘an extended form of history taking’ .
(100)
Within certain psychodynamic approaches formulation is commu-nicated formally to patients (e.g. by letter in cognitive analytic therapy Ryle
(101)).
The middle phase
(a)  Supportive and directive interventions in 
psychodynamic therapy
Supportive techniques are used both explicitly and implicitly in 
psychodynamic treatment. They include offering explicit support and afﬁ  rmation; offering reassurances concerning, for example,

psychodynamic treatment. They include offering explicit support and afﬁ  rmation; offering reassurances concerning, for example, 
irrational anxieties about the therapeutic arrangements; expressing concern and sympathy to a patient who has suffered a recent loss; and general empathy for the patient’s anxieties and struggles with the treatment.
(102)
From a psychodynamic point of view, such supportive interven-
tions are by no means straightforward. For example, Feldman(103)
illustrated how patients may sometimes experience the therapist’s submission to a demand for reassurance as a source of anxiety rather than comfort. They may be unconsciously aware that the therapist’s true stance is not compatible with reassurance and therefore face anxieties about the therapist’s weakness in allowing themselves to be manipulated. By contrast, Kohut’s
(17) emphasis on

(17) emphasis on 
interpersonal empathy was probably a welcome antidote to the somewhat rigid interpretive stance of American ego psychologists, particularly for those whose history of psychosocial deprivation meant that they had experienced little by way of genuine warmth or concern in the past.
The most common use of supportive and directive techniques in 
psychodynamic psychotherapy are in the service of the therapy itself. Elaborative techniques (e.g. the simple question: ‘Could you tell me more?’) are undoubtedly directive in specifying a topic of interest, but at the same time may be crucial antecedents to interpretive work. Clariﬁ  cation stands in between supportive and 
interpretive interventions. It is a restatement in the therapist’s words of the patient’s communication. It may also be crucial in 
offering a verbal (symbolic) label for a confused set of internal

offering a verbal (symbolic) label for a confused set of internal 
experiences which the patient is poorly equipped to represent coherently. Confrontation is also in between a directive and an interpretive approach. At its gentlest, confrontation may involve the therapist simply identifying an inconsistency in the patient’s communication and bringing this to the patient’s attention. For example: ‘Y ou seem to express no sadness about this loss, yet in the past you claimed to have cared a great deal for him’ .
(b) Regression

An important facet of psychoanalysis and long-term psychodynam-ic therapy is the activation and exploration of parts of the patient’s personality which may be normally hidden behind an over-riding demand to adapt to the demands of every day life. Access to these aspects of personality is achieved through the process of regression. It has been suggested that rather than encouraging regression, the 
process is best conceived of as inhibiting ‘an anti-regressive func-tion’ in much the same way that certain intimate interpersonal experiences, large group situations, and alcohol appear to bring out the more infantile aspects of our character.
(104) Some psychoana-
lysts consider regression to be crucial to successful psychoanalytic treatment, but others consider the concept and its clinical applica-tion outmoded and counterproductive.
(105) The extent to which a 
particular treatment involves signiﬁ  cant regression appears to be a

particular treatment involves signiﬁ  cant regression appears to be a 
function of the patient’s personality as well as the therapist’s par-ticular approach. Fear of regression is an important source of resis-tance to long-term psychotherapy, particularly amongst those with previous experience of psychotic episodes.
(104)
(c) Resistance
Resistance is inevitably encountered in any long-term psychody-namic treatment. In fact, the presence of resistance is implied by the term dynamic, which suggests psychic forces both pulling against and pushing towards change. Like regression, resistance ﬂ  uctuates 
in the middle stage of treatment. In borderline and narcissistic disorders, the patient’s intense resistance signals the patient’s desperation to protect extremely fragile self-esteem. In less severe cases, what appears to be at issue is preventing a painful integration of experience, such as the integration of love and hate directed towards the same object.

(106)
In clinical practice resistance takes a variety of forms. In repres-
sion resistance, the patient may experience a temporary difﬁ  culty 
in gaining access to particular ideas and feelings; for example, failing to remember dreams. In transference resistance the patient may appear to wish to keep their relationship with their therapist at an extremely superﬁ  cial level. In a negative therapeutic reaction the 
increase of symptomatology occurs alongside therapeutic progress. In Freud’s formulation this may be attributed to unconscious guilt. It is quite likely that in at least some patients this form of resistance against psychotherapy is part of a pervasive so-called ‘envious’ pre-disposition to eradicate any aspect of their life that they experience as ‘good’ but beyond their immediate control.
(107)
(d) The experience of the transference

(107)
Patients may experience a whole range of feelings about an analyst including love, admiration, excitement or anger, disappointment, and suspicion. The feelings appear to have little to do with the therapist’s actual personality as different patients are likely to bring quite disparate feelings about the same analyst at the same time. While clearly not realistic, the actual nature of transference experience and its use in therapy is quite controversial.
(108) Object-
relations theorists consider the analyst a vehicle onto which an internal object (a person, an aspect of a person, the self, or an aspect of the self) is projected.
(109) Clearly internal objects are representa-
tions which are heavily distorted by both fantasy and defensive processes.
For John Bowlby
(64) transference feelings are based on expecta-

tions gathered through past relationship experience with an attach-ment ﬁ  gure. Patients resist understanding of the past relationship 
by insisting on repeating it. Bowlby’s
(110) suggestion that therapists 
function as secure bases implies that psychodynamic therapists are, in part, conducting attachment therapy as inevitably they serve as attachment ﬁ  gures for their patients. There is accumulating evidence 
for this claim
(111–114) with a number of studies linking speciﬁ  c

1343
transference schemas and attachment.(115–117) Many analysts do 
not accept such an isomorphism between past and present. Rather, they see it as something which gives coherence to the patient’s experience of the analytic relationship—an aspect of narrative rather than a representation of the historical realities of the patient’s experience.
(118) In contrast, analysts who work in the Klein–Bion 
frame of reference see transference as providing an inevitably accu-rate picture of the patient’s current internal world.
(119) For exam-
ple, a transference where the analyst is idealized may reﬂ  ect psy-
chotic anxieties in the patient linked to an intensiﬁ  cation of the 
death instinct. The idealization serves to protect both the patient and the analyst from fantasized destruction which threatens to engulf them both. Marcia Cavell
(120) demonstrated that these alter-

native models of transference have their philosophical roots in the debate between correspondence and coherence models of truth.
There is signiﬁ  cant debate regarding from what point and how 
much psychoanalytic therapists should work ‘in the transference’ . Some analysts are inclined to see transference as pertinent to every aspect of the psychoanalytic situation. For example, Joseph
(119)
considers the therapeutic situation in toto as mirroring the internal state of the patient. Thus the therapeutic alliance or the ‘real relationship’
(121) are regarded as subsumed under the transference 
relationship. In this context it makes little sense to interpret any-thing other than the transference from the very beginning of the analysis. By contrast, Strachey

(122) understood transference as an

(122) understood transference as an 
attempted externalization of the patient’s superego. Unlike other people in the patient’s life, the analyst does not accept this exter-nalization, whether it is idealized, denigratory, or judgemental. The analyst conveys his or her understanding of the externalization by a so-called ‘mutative interpretation’ . While Strachey implied that only interpretation of the transference is therapeutic, his view clearly admits other aspects of the therapeutic relationship. Other therapists, particularly Freudian psychoanalysts, regard transference interpretations as an important but not uniquely therapeutic way of providing the patient with insight and consider the almost exclusive reliance on understanding the patient through their thoughts and feelings about their therapists as unhelpful and even dangerous.
(123) The only systematic investigation of this technical

(123) The only systematic investigation of this technical 
controversy, where patients were randomly assigned to a transfer-ence and a non-transference-oriented psychological therapy, could not show a signiﬁ  cant difference between the overall effectiveness 
of these two treatments, although there was a tendency for those with more dysfunctional object-relationship representations to do better in therapy which used transference interpretations.
(124,125)
The nature of the transference appears to systematically relate 
to speciﬁ  c clinical groups and hence may have an aetiological 
signiﬁ  cance. For example, speciﬁ  c transference patterns appear 
to characterize particular groups of narcissistic patients.(17) The

to characterize particular groups of narcissistic patients.(17) The 
‘mirroring’ transference is one where patients crave the approba-tion and admiration of the therapist. This may be a consequence of the failure of the original self-objects (parents) in their mirror-ing function. If this transference is undermined by premature interpretations, an opportunity for restoring self-esteem is lost. The ‘idealizing’ transference also enables the patient to address a deﬁ ciency in self-esteem by secretly identifying with the object of 
admiration (the analyst). If the analyst destroys this idealized image, within Kohut’s framework, this is equivalent to a direct attack on the patient’s self-regard. Other analysts would suspect that behind such an exaggeratedly positive image lies the patient’s true image of the analyst as frustrating or inadequate, an image

which is simply placed out of harm’s way by the idealization. An interesting empirical study of clinicians’ experience of the 
transference with personality disordered patients was reported 
from Drew Westen’s laboratory.
(115) The study identiﬁ  ed ﬁ  ve trans-
ference dimensions: angry/entitled, anxious/preoccupied, avoidant/counterdependent, secure/engaged, and sexualized which were associated in predictable ways with Axis II pathology and conﬁ  rmed 
that the way patients interact with their therapists can provide important data about their personality, attachment patterns, and interpersonal functioning.
Commonly, transference includes an erotic component, regard-
less of the age or even the gender of the analyst.
(126) Admitting to 
such feelings may border on the unacceptable for some patients. Attachment theorists may suggest that sexual fantasies are used in the service of obtaining the attention of an unresponsive attach-ment ﬁ  gure.

(127) Eroticized transference, relatively common in 
severely traumatized patients, represents an expression of a need for sexual gratiﬁ  cation which, in the context of the therapy, is not 
considered by the patient as unrealistic.
(71) Some view this phe-
nomenon as an indication of an immature mode of representing internal reality, where only the physically observable outcome is believed to be real.
(128)
(e) Experience of the countertransference
Countertransference is a somewhat controversial concept in psycho-analytic clinical work. The therapist during the course of an inten-sive long-term treatment is likely to have a range of feelings which are related to the patient’s current experience but which may serve to either illuminate or obscure this. Some countertransference experi-ences may be instances of projective identiﬁ  cation and thus can be 
appropriately attributed to the patient,
(129) whereas others are likely

(129) whereas others are likely 
to be the analyst’s neurotic emotional reactions to the patient’s behaviour or the material he or she brings. For Freud,
(130) counter-
transference was always of this latter type, a neurotic reaction which was likely to obstruct psychoanalytic treatment. It was not until Paula Heimann
(131) pointed out that the analyst’s feelings and 
thoughts could contain important clues about the patient’s uncon-scious mental state that countertransference started to be seriously considered as part of the analyst’s therapeutic armamentarium. Those following an interpersonalist tradition saw the recognition of the complementarity of the therapeutic relationship as highly appro-priate. From this point of view, the assumption of perfect neutrality on the part of the analyst who is a participant as well as an observer is both an anathema and an anachronism.
(132) The psychotherapeu-

tic process is more accurately viewed as a complex mixture of com-plementary interpersonal processes which establish themselves in ‘custom designed’ conﬁ  gurations in each treatment.
(133)
The therapist’s feelings may be either complementary to or 
concordant with those of the patient.(134) Concordant counter-
transferences are the product of primitive, empathic processes within the therapist who ‘feels’ for the patient, who may uncon-sciously react to experiences implied but not yet verbalized by the patient; for example, inexplicable overwhelming sadness. Complementary countertransferences tend to occur when the patient treats the analyst in a manner consistent with interpersonal interactions within a past relationship. Most commonly this occurs when the patient treats the therapist as he or she experienced being treated as a child. This is known as the ‘reverse transference’ .
(135)6.3.5 psychoanalysis and other long-term dynamic psychotherapies

SECTION 6  treatment methods in psychiatry 1344
The mechanisms of countertransference are poorly understood. 
T o assert that countertransference functions via projective identiﬁ  -
cation merely brings one poorly understood phenomenon to account for a second even less well understood one. Sandler
(136)
suggested that an instantaneous process of automatic mirroring of 
one’s partner in an act of communication accounted for concor-dant countertransference. The process, which he termed primary identiﬁ  cation, was non-conscious and could be brought into aware-
ness only upon reﬂ  ection. Recent work on the mirror neurone sys-
tem
(137,138) suggests that the fundamental mechanism that allows

tem
(137,138) suggests that the fundamental mechanism that allows 
us to understand the actions and emotions of others involves the activation of the mirror neurone system for actions and the activa-tion of visceromotor centres for the understanding of affect. An alternative account suggests that a secondary mode of encoding is available within language whereby the use of a language of pretend gestures at the phonemic, syntactic, or even semantic level enables the communicator to address directly the unconscious of the recipi-ent of the communication.
(139) In other words, anything that can be 
said in gestures may be communicated unconsciously through lan-guage, through phonemic distortion, intonation, and other paralin-guistic features and picked up impressionistically by the therapist.
When either concordant or complementary countertransferences

When either concordant or complementary countertransferences 
mobilize defensive processes within the analyst, countertransference is in danger of becoming disruptive to therapeutic understanding. The analyst may react by unconsciously withdrawing from the therapeutic relationship. For example, in the case of a concordant countertransference where the patient’s feelings of inadequacy create a similar feeling in the analyst, the analyst’s vulnerability in this area may lead him or her to become defensively angry or exces-sively motivated to demonstrate his or her efﬁ  cacy. There may be 
no simple way of regulating such reactions and the only reasonable strategy might be to carefully monitor one’s style of relating, noting 
anything that is unusual. A number of analysts have pointed to the 
importance of reﬂ  ectiveness in this context.
Some feelings in relation to the patient are not provoked either

Some feelings in relation to the patient are not provoked either 
by the patient’s projections or the neurotic feelings these give rise to in the therapist. It required someone of the stature of Donald Winnicott
(140) to make the self-evident observation that the 
provocative behaviour of certain patients (particularly those in the borderline spectrum) can lead to a normal reaction of ‘objective hate’ . These reactions are merely indications of the therapist’s humanity. Analytic understanding of these sometimes intense reactions to patients helps, but models of countertransference ill-ﬁ  t 
such experiences. The objective study of countertransference has had to wait for a recent ingenious methodological development from Westen’s laboratory.
(141)  The Countertransference

(141)  The Countertransference 
Questionnaire yielded eight clinically and conceptually coherent factors that were independent of clinicians’ theoretical orientation: (i) overwhelmed/disorganized, (ii) helpless/inadequate, (iii) positive, 
(iv) special/overinvolved, (v) sexualized, (vi) disengaged, (vii) pare ntal/
protective, and (viii) criticized/mistreated. Countertransference patterns were systematically related to patients’ personality pathol-ogy across therapeutic approaches, suggesting that clinicians, regardless of therapeutic orientation, can make diagnostic and therapeutic use of their own responses to the patient.
(f) Interpretation

Interpretive interventions are at the core of psychoanalytic and psy-chodynamic treatment. However, the importance of interpretation is often exaggerated in relation to other aspects of the therapy. 
It is a sobering reminder that follow-up studies of long-term psychodynamic therapies invariably demonstrate that patients remember their analyst not for their interpretive interventions, rarely remembering individual interpretations, but rather for their ‘emotional presence’ , regardless of the analyst’s therapeutic perspective.
(142)
Interpretations may be classiﬁ  ed according to the aspect of a 
conﬂ  ict they aim to address: the defence, the anxiety, or the under-

(142)
lying wish or feeling. Similarly, the content of the interpretation may be used in classifying interpretations: whether it relates to external reality, the transference relationship, or childhood rela-tionships. In principle, in the earliest phases of treatment interpre-tations relating to current events are most common and, as the treatment progresses, transference issues and the patient’s past may increasingly take over as foci of analytic work. Interpretations should start with the patient’s anxiety, by identifying the defence used by the patient to protect himself from repudiated wishes and affects. In reality, these are guidelines that are rarely followed in practice. For example, very long-term treatments tend to end up being principally supportive explorations of the patient’s current experience.

(143) Furthermore, interpretations of the distant past 
tend to be least helpful to individuals with severe personality disor-ders.
(144) Working in the so-called ‘here and now’ is more effective 
with those patients whose representation of the past is unreliable and distorted.
(145)
Steiner(146) distinguished analyst-centred from patient-centred 
interpretations. The former refers to comments on the patient’s reactions in terms of what the patient thinks may be going on in the analyst’s mind, while the latter directly addresses the analyst’s perception of the patient’s non-conscious mental state. In either case the patient is directly learning about how minds interact in the context of social relationships. The distinction is important since when patient-centred interpretations are used exclusively the ther-apist may appear to be persecutory and not to be cognizant of the patient’s genuine difﬁ  culties in being in an intimate relationship

with another person. Others have argued, that at least in the case of severe personality disorder, interpretations, if they were to have therapeutic value, should focus on the patient’s understanding of thoughts and feelings in themselves or in others at the level of what 
was conscious rather than unconscious, what patients could dis-
cover for themselves rather what they received as a communication from a ‘mind expert’ .
(147) This implies that interpretation of the 
transference is about helping the patient represent their own and their therapist’s mental states in the treatment room in all their complexity but with a stance conveying enquiry and playful curios-ity about something that is not readily knowable (the mental state of the other is always opaque) with the aim of making thinking about thoughts and feelings safe again rather than communicating 
powerful insights.
The idealization of the transference has led some therapists to

The idealization of the transference has led some therapists to 
neglect interpretation of the patient’s behaviour outside of the therapy. Most clinicians now agree that a balance needs to be struck between these two approaches. Treatment which is over-focused on the transference becomes a claustrophobic enclave.
(148) In certain 
instances, the direct communication of the therapist’s experience of frustration (objective hate in Winnicott’s terms) may help to break a rigid repetitive pattern in the therapy.
(149) Disclosing the 
therapist’s experience is one of the cutting edges of the relational

1345
approach to psychodynamic therapy.(150) In cases where the thera-
peutic alliance falters, perhaps following an empathic failure on the part of the therapist, it turns out that the recovery of the alliance may have particular therapeutic value both in showing the possibility of repair
(151) but also as an opportunity to understand 
misunderstanding, an ideal opportunity for the recovery of mentalization.
(152)
Ending treatment
The ending of psychoanalytic therapy is often idealized in clinical descriptions. As there is little agreement on the goals of psychoana-lytic therapy,
(79) it is hardly surprising that there is little general 
agreement about when ending is appropriate. Desirable ﬁ  nal out-
comes are mostly stated in terms of the process of treatment and are thus mostly speciﬁ  ed in theoretical terms (e.g. increased aware-
ness of impulses and fantasies, a reintegration of aspects of the self lost through projective identiﬁ  cation, the capacity to engage in

ness of impulses and fantasies, a reintegration of aspects of the self lost through projective identiﬁ  cation, the capacity to engage in 
self-analysis, etc.). All these, even if observable in the course of treatment, are only loosely related to the aims the patient might have in concluding a lengthy treatment process.
The patient’s own goals tend to be outcome rather than process 
goals and are more easily defined: the decline of symptoms, improved relationships, greater well-being, increased capacity for work, higher self-esteem, a capacity for assertiveness. As such changes are clearly achievable without psychodynamic treatment, 
many psychodynamic clinicians erroneously regard such criteria 
for ending as superﬁ  cial. Independent evidence will be required to 
show that the achievement of process aims results in a more permanent or general achievement of outcome aims, in order to validate process aims as an appropriate criterion for ending.

Ending itself, of course, is a process. There is signiﬁ  cant disagree-
ment between authors, however, as to its nature; it has been labelled among other things as a mourning,
(153) a detachment,(71) and a 
maturation.(154) It is inevitable that there is disappointment and 
disillusionment at the ending of long-term therapy as what is achieved is never quite the same as what has been hoped for.
(155)
Also, the patient loses the object who has been available as a recep-tacle for projections.
(146) It is not surprising then, that symptoms 
sometimes return, even if only brieﬂ  y, as part of the process of ter-
mination and the full beneﬁ  t is not seen until some months after 
termination.(25) There is general agreement, however, that with

termination.(25) There is general agreement, however, that with 
these unconscious issues worked through the ending of therapy requires no special form of intervention on the part of the thera pist.
Efﬁ cacy
It is often said that there are no studies on the effectiveness of 
psychoanalysis and long-term psychodynamic psychotherapy. In fact, this is not true. There are a number of comprehensive reviews
(156–160)  and they tend to come to similar conclusions. There 
is considerable evidence for the effectiveness of psychoanalytic approaches but deﬁ  nitive randomized controlled trials of its efﬁ  cacy 
are still lacking.
The Boston Psychotherapy study
(161) compared long-term psy-

choanalytic therapy (two or more times a week) with supportive therapy for clients with schizophrenia in a randomized controlled design. On the whole clients who received psychoanalytic therapy fared no better than those who received supportive treatment. In a partial-hospital RCT
(162,163) the psychoanalytic arm of the treatment included therapy groups three times a week as well as 
individual therapy once or twice a week over an 18 month period.
The Stockholm Outcome of Psychotherapy and Psychoanalysis 
Project(164–166)  followed 756 persons who received national insurance 
funded treatment for up to 3 years in psychoanalysis or psychoana-
lytic psychotherapy. The groups were matched on many clinical variables. Four or ﬁ  ve times weekly analysis had similar outcomes

lytic psychotherapy. The groups were matched on many clinical variables. Four or ﬁ  ve times weekly analysis had similar outcomes 
at termination when compared with one to two sessions per week psychotherapy. During the follow-up period, psychotherapy patients did not change but those who had had psychoanalysis continued to improve, almost to a point where their scores were indistinguishable from those obtained from a non-clinical Swedish sample.
The German Psychoanalytic Association undertook a major 
follow-up study ( n = 401) of psychoanalytic treatments undertaken 
in that country between 1990 and 1993.
(159,167) Between 70 per cent

(159,167) Between 70 per cent 
and 80 per cent of the patients achieved (average 6.5 years after the end of treatment) good and stable psychic changes according to the evaluations of the patients, their analysts, independent psychoana-lytic and non-psychoanalytic experts, and questionnaires com-monly applied in psychotherapy research. The evaluation of mental health costs showed a cost reduction through fewer days of sick leave during the 7 years following the end of long-term psychoana-lytic treatments. In the absence of pre-treatment measures it is impossible to estimate the size of the treatment effect.
The Research Committee of the International Psychoanalytic 
Association recently prepared a comprehensive review of North American and European outcome studies of psychoanalytic treat-ment.

(157) Four case record studies, 13 naturalistic pre-post or 
quasi-experimental studies, nine follow-up studies, and nine exper-imental studies were identiﬁ  ed. In addition, six process-outcome 
studies were also reviewed. The committee concluded that existing studies failed to demonstrate unequivocally the efﬁ  cacy of psycho-
analysis relative to either alternative treatment or active placebo. Studies showed a range of methodological and design problems including absence of intent to treat controls, hetero geneous patient groups, lack of random assignments, failure to use independently administered standardized measures of outcome, etc.
Another overview
(168) suggested that psychoanalytic treatments

(168) suggested that psychoanalytic treatments 
may be necessary when other treatments proved to be ineffective. The authors concluded that psychoanalysis appears to be consis-tently helpful to patients with milder disorders and somewhat helpful to those with more severe disturbances. More controlled studies are necessary to conﬁ  rm these impressions. A number of 
studies testing psychoanalysis with ‘state of the art’ methodology are ongoing and are likely to produce more compelling evidence over the next years. Despite the limitations of the completed stud-ies, evidence across a signiﬁ  cant number of pre-post investigations 
suggests that psychoanalysis appears to be consistently helpful to patients with milder (neurotic) disorders and somewhat less consistently so for other, more severe groups. Across a range of uncontrolled or poorly controlled cohort studies, mostly carried 
out in Europe, longer intensive treatments tended to have better

out in Europe, longer intensive treatments tended to have better 
outcomes than shorter, non-intensive treatments (demonstration of a dose-effect relationship). The impact of psychoanalysis was apparent beyond symptomatology, in measures of work function-ing and reductions in health care costs. Studies report results which other psychotherapies have not been able to achieve; some studies show very long-term beneﬁ  ts from psychoanalytic treatment; the 6.3.5 psychoanalysis and other long-term dynamic psychotherapies

SECTION 6  treatment methods in psychiatry 1346
results tend to be highly consistent across studies; some of the 
populations studied have been larger than most better controlled treatment trials. So whereas it is true to say that little that is deﬁ  nite 
can be stated about the outcome of psychoanalysis, a number of suggestive conclusions may be drawn and these are listed below.
Across a number of studies and measures psychoanalysis has 
been shown to beneﬁ  t the majority of those who are offered this 
treatment
(169) and can bring the functioning of a clinical group to 
the level of the normal population.(167) Completed treatments tend 
to be associated with greater beneﬁ  ts.(170) On the whole longer 
treatments have better outcomes(171) and intensive psychoanalytic 
treatment is generally more effective than psychoanalytic psycho-therapy,
(25) but its superiority sometimes only becomes apparent 
on long-term follow-up.(172) Psychoanalysis can lead to a reduction

on long-term follow-up.(172) Psychoanalysis can lead to a reduction 
in health care related use and expenditure(173) and this is main tained 
for a number of years after therapy ends(174) but it does not invari-
ably achieve this.(166) Psychoanalytic treatment can lead to a reduc-
tion in the use of psychotropic medication amongst inpatients.(175)
Long-term psychoanalytic therapy can reduce symptomatology in severe personality disorders such as BPD
(162,176,177)and these 
improvements are maintained.(163)
Training
Training in psychoanalytic psychotherapy and psychoanalysis has three components: a personal psychoanalytic psychotherapy, theoretical training, and supervised clinical practice. A variety of trainings are available, although in most countries there is only one training organization that is recognized by the International Psychoanalytic Association. Training is long, chieﬂ  y because of the

length of supervised treatments. Training standards are carefully monitored by national and international bodies.
Psychoanalysis is hardly a practical treatment alternative for the twenty-ﬁ  rst century. The principles derived from this treatment, 
however, have powerfully influenced other psychotherapeutic approaches, whether long-term or short-term therapy or psychiat-ric care more generally, particularly in the United States. At the time of its invention, it was the unique effective psychosocial treat-ment method for psychiatric disorder which offered a genuine alternative to the sometimes barbaric and generally ineffective treatment methods available. Not surprisingly, its proponents 
adopted an almost religious zeal in defending its value against

adopted an almost religious zeal in defending its value against 
alternative approaches. While understandable, such an attitude has no place in the sophisticated evidence base underpinning multi-agency service planning. Psychoanalytic clinicians face a challenge in identifying their niche in the complex mental health care delivery systems of the twenty-ﬁ  rst century.
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6.3.6 Group methods 
in adult psychiatry
After a century of development, group therapy is today one of the 
most widely practised treatment methods in psychiatry with an extensive literature. There are three principles common to its wide range of applications. First, the therapist calls the ‘community’ into the consulting room where, together with the therapist, it becomes the therapeutic agent. Second, the therapist assembles a group of people who can contribute to a commonly held resource from which its members can each derive beneﬁ  ts. And third, the thera-

pist does nothing for them in the context of the group, that they can do for themselves, and one another.This chapter starts by providing a conceptual framework that 
differentiates methods, models, and applications for the practice of group therapy in adult psychiatry. After classiﬁ  cation of the dif-
ferent methods and applications we discuss the main theoretical models; explore the dynamic life of therapy groups; consider some of the key clinical issues facing practitioners; their applications to a range of patient populations and settings; their evaluation and justiﬁ  cation and their historical evolution this century. In the con-
clusion we consider the planning of group services and the training of their practitioners. This revision of the chapter has brought it up-to-date with the contemporary literature in a ﬁ  eld that has seen 
a great deal of innovation since the original 2000 edition.
The developing evidence base for group psychotherapy is

The developing evidence base for group psychotherapy is 
‘Guardedly optimistic. The literature has become stronger and deeper and is capable of supporting evidence-based treatment recommendations for some patient populations.’ The evidence base for the effectiveness of group psychotherapy has been growing with the ﬁ  eld. Some 700 studies, spanning the past three decades, have 
shown that the group format consistently produced positive effects with diverse disorders and treatment models.
(1) These show that 
both individual and group psychotherapy will effect much the same set of results. For group therapy to be effective it has to utilize those therapeutic factors originally laid out by Foulkes
(2) and later 
by Yalom(3)—the group has to be the primary focus of therapy;

by Yalom(3)—the group has to be the primary focus of therapy; 
patients need to be well selected; and therapists need to be ade-quately trained. The chapter will address these questions of focus, selection, and training.
Although the two authors of this chapter are both group analysts, 
we have set out to provide a full account of the wide range of group work practice. The United Kingdom is our own working location which lends emphasis to the chapter but it is compiled with sources and references that address the international ﬁ  eld and it gives 
attention to current literature in many countries including North and South America and Continental Europe.
Basic methods
In Fig. 6.3.6.1 we have used two simple factors—therapeutic goals and group leadership—to provide a simple classiﬁ  cation of the 
many different methods.
Therapeutic goals
Groups will be more or less speciﬁ  c in their therapeutic goals. For

Groups will be more or less speciﬁ  c in their therapeutic goals. For 
example, those catering for a homogeneous population with a com-monly deﬁ  ned problem whose solution provides the basis for entry 
to the group—such as overcoming drink or drug dependence—are classiﬁ  ed here with speciﬁ  c goals. Groups that provide psychoana-
lytic psychotherapy, whether run according to Interpersonal, Tavistock, or Group-Analytic models, are classiﬁ  ed here with non-
speciﬁ  c goals. There is a wide range of variation between these 
extremes and within each of these main psychodynamic models.

The more the leader directs the group, the more prominent he becomes as the group’s ‘model object’ . The less the leader directs the group, the more scope there is for the emergence of unconscious dynamics and for attention to transference and counter-transference. In this case, therapy progresses through the development of relationships. The greater the leadership activity, the more likely it

1351
is that group members are being offered a technique or skill in the 
setting of a group. The lower this activity, the stronger will be the 
relational content of the therapy and the therapist’s skills of foster-
ing relationships will equip the group to work developmentally and 
in depth on both the obvious and hidden issues that its members 
bring. The three principal psychodynamic methods discussed in 
The principal model of psychodynamic  group therapy below share 
a non-directive philosophy with subtle but signiﬁ  cant differences 
between their models of practice.
Using these two basic indicators—speciﬁ  city of goals and levels 
of leadership activity—the four quadrants in the diagram provide 
us with a simple way of ‘placing’ the different group therapies.
Goal-speciﬁ  c therapy with high level of leader 
activity: quadrant 1
In many drug and alcohol dependency regimes, participants are 
required to fulﬁ  l obligations tied to each stage of a structured

required to fulﬁ  l obligations tied to each stage of a structured 
programme. They move forward when stage-speciﬁ  c obligations 
are fulﬁ  lled. As the novice moves up, he/she becomes a trainer to 
the newcomers with the therapist(s) directing the process in active 
terms. Cognitive therapy given in a group setting uses the group 
as an assembly who learn from and discuss with the expert. 
Dependency on a shared and valued leader, and attention to group 
dynamics amplify the learning and some group cohesion develops, 
but this is not the primary focus of the therapy.
Goal-directed with lower level of leader 
activity: quadrant 2
Problem-solving or psycho-educational groups for homogeneous 
populations, such as those set up for eating disorders or offenders, 
which are run along analytic lines, can be placed in this category. 
Although there are clear and directed goals, the leader’s level of

Although there are clear and directed goals, the leader’s level of 
activity is conﬁ  ned to a facilitating, linking, or enabling one, fol-
lowed by analysis and interpretation. Group discussion and cohe-
sion amplify the affective experience and enhance the learning.
Non-speciﬁ  c goals with high level of leader 
activity: quadrant 3
In psychodrama groups , leadership is explicitly vested in the 
psychodrama director. The needs and goals of group members are diffuse and often diverse and, in psychiatric practice, will have to 
do with relief from mental suffering. The psychodrama director 
can draw on many techniques. Affective arousal can be high so the 
power of sharing through discussion and the sympathy; and empa-
thy of group members towards one another become powerful ther-
apeutic tools. Strong conﬂ  ict arousal and its subsequent resolution 
is similarly therapeutic.

Systems-centred therapy  (as developed by Agazarian)(4)
similarly provides a high level of leadership activity for groups that 
have non-speciﬁ  c goals. Short-term dynamic groups are frequently 
constituted with non-speciﬁ  c goals but are run over 10 or 20 sessions 
by leaders who maintain a high level of involvement and direction, 
often demarcated according to the different stages of the group’s 
progress.
Non-speciﬁ  c goals with low level of leader 
activity: quadrant 4
The goals of group-analytic or psychoanalytic group therapy are 
most frequently diffuse and non-speciﬁ  c involving relief from 
symptoms and other forms of suffering; personal growth; and 
psychological change. There are three main schools considered in 
this chapter—the Interpersonal (Y alom), Tavistock (Bion or group-

as-a-whole), and the Group-Analytic. They share non-speciﬁ  c 
goals and have low levels of leader activity but differ from one 
another in how the leadership role and function is understood 
and discharged. They share assumptions about the importance 
of unconscious individual and group dynamics and look to the 
group for its transformational potential. Their differences affect 
the way in which transference and counter-transference is under-
stood and worked with. There is a comparative appraisal of these 
models below.
The application of basic methods
We now provide a more detailed overview of the current ﬁ  eld 
and offer a brief set of training requirements for practitioners in 
each of the methods discussed.
The ﬁ  eld can be divided into ﬁ ve basic methods —activity,

The ﬁ  eld can be divided into ﬁ ve basic methods —activity, 
supportive, problem-solving, psycho-educational, and psychody-
namic. The ﬁ  rst three methods are goal-speciﬁ  c as indicated by 
their descriptions, the fourth is less speciﬁ  c and the ﬁ  fth is a non-
directive analytic psychotherapy. In supportive and problem-solving
groups, therapeutic leadership can be highly directed or not, 
depending on the approach. Activity and psycho-educational 
groups will inevitably have a high level of directed group leader-
ship, whilst psychodynamic groups have a much lower level of 
directed group leadership. All ﬁ  ve methods rely on the same basic 
procedures—the selection and grouping of a number of people 
seeking help who have regular meetings together with one or more 
well-trained therapist(s).
Activity groups
The most vulnerable and disturbed patients can be placed in therapy

The most vulnerable and disturbed patients can be placed in therapy 
groups deﬁ  ned by an activity that provides a convening function 
such as exercise or cooking. They can then be used to create condi-
tions for a wide range of secondary functions that foster afﬁ  lia-
tions, develop social skills, address unspoken anxieties, and express 
troubling emotions. Occupational therapists and nurses using 
art media or other socially syntonic activity like gardening or Fig. 6.3.6.1 A simple classiﬁ  cation of group methods.
6.3.6 group methods in adult psychiatry

SECTION 6  treatment methods in psychiatry 1352
hair-dressing have been developing a wide range of group services 
in both acute and rehabilitation psychiatry for many years.(5) The 
approach has been used in a wide range of other settings including medical rehabilitation, rehabilitation with refugees, social work and fostering, and adoption programmes. Groups that keep the original activity as their primary focus, working with art media for example, need to be differentiated from those which use such media to develop an analytic focus on psychological work. The arts psychotherapies belong to this latter group. They have non-speciﬁ  c 
therapeutic goals and might, as in the case of music therapy, have a high level of leadership activity or, in the case of art therapy, have a low level of leadership activity.
Whilst therapists do not engage in the uncovering and explora-

tion of unconscious dynamics, they will need leadership abilities, capabilities in organizing group activities, and should have a basic understanding of psychopathology and group dynamics.
Supportive groups
These groups function as a form of social support providing con-tainment, the improvement of social skills, and the enhancement of participants’ capacities for social adaptation. They aim to reduce the deleterious effects of social isolation, bring people out of withdrawal into a social context, and provide opportunities for problem sharing. They cater to patient populations with long-standing personality disorders not open to uncovering exploration; those with chronic mental and physical illness,
(6) physical handi-
cap, mental retardation, and carers for those with any of these problems. They will often allow a certain amount of psycho-education with the group leader inﬂ  uencing members’ attitudes

cap, mental retardation, and carers for those with any of these problems. They will often allow a certain amount of psycho-education with the group leader inﬂ  uencing members’ attitudes 
as in the case, for example, of a group for young sexually active adults with learning disability who might receive guidance on contraception.
Problem-solving groups
Group therapy is provided for a set of referral criteria to resolve a defined and sometimes circumscribed problem. Alcoholics 
Anonymous, Alanon, Gamblers Anonymous, and groups for people 
with poor impulse control, eating disorders, or other habitual 
problems such as smoking, are a few of the examples. These groups

problems such as smoking, are a few of the examples. These groups 
can take on many of the features of long-term support groups, in that they offer ego-supportive and adaptive resources, providing an extended service for monitoring by the patient or by professionals, without necessarily committing members to the deeper and more radical analytic work entailed by a psychodynamic group. In many cases, the problem-solving focus provides a convening frame by which to engage a population who are soon drawn into psychody-namic work that sees them through profound changes. Many of the groups run by clinicians in primary hospital care—occupational therapists, nurses, doctors, and psychologists—take this form. The Group Work Programme at the Medical Foundation For Victims Of T orture in London is another example (see also section on trau-ma in specical population, below).

Where they cater for the more severely disturbed, staff will 
need to be well-trained in one of the core professions. They will need leadership abilities, capabilities in organizing group activities, 
should have a basic understanding of psychopathology, and be suf-ﬁ ciently well-trained to explore the dynamic group issues that lead 
from the problem back to the personality structure of their mem-bership. If therapeutic goals involve major changes in personality and social functioning, this will involve the uncovering and explo-ration of unconscious dynamics.
Psycho-educational groups
The original groups for servicemen with war neurosis at Northﬁ  eld took this form in which people were given the role of

The original groups for servicemen with war neurosis at Northﬁ  eld took this form in which people were given the role of 
students of their disorders rather than ‘sick’ people. Patients become open to new information and are better able to unlearn maladap-tive attitudes about the nature of their disorder. This more cogni-tive approach can be applied in homogeneous problem-solving groups. Information can be provided through lectures, discussions, and suitable reading material. There are different ways of lowering anxiety and uncovering maladaptive and inappropriate attitudes towards such problems as anxiety states, phobias and obsessions, and psychosomatic disorders. Many of the groups run for those with serious physical illness (see also section on the medically ill in special populations, below) take this form. And there is often a major psycho-educational component in support groups—for example, those with chronic mental illness who can be helped to

understand and cope with delusions, hallucinations, and the stigma of illness.
(7)(see also section on the mentally ill in special popula-
tions, below)
Staff need leadership abilities; capabilities in organizing group 
activities, a basic understanding of psychopathology, and need to be sufﬁ  ciently well-trained in their chosen problem area to be able 
to relate its educational focus to thematic group issues. If therapeutic goals involve major changes in personality and social functioning, this will involve the uncovering and exploration of unconscious dynamics.
Psychodynamic groups
There are supportive, problem-solving, and psycho-educational components in all psychodynamic groups, but the description ‘psychodynamic’ is reserved for those in which the declared goal is 
lasting personal change through a non-directive, free-associative 
therapy. The range of different group contexts is so varied that—at 
ﬁ rst sight—they might appear to have little in common. But there

ﬁ rst sight—they might appear to have little in common. But there 
will be common principles offering therapy to a group of people 
on an in-patient unit recovering from psychosis and meeting thrice 
weekly; those in a secure unit for violent offenders meeting once weekly; and those—including mental health trainees—attending a group in private practice once or twice weekly. These principles can be summarized in the table, Table 6.3.6.1 below.
Within these parameters therapy is part of the cultural domain 
of all shared, conversational experience in which people struggle with meaning—in congregational life, in the confessional, in theatre, narrative or poetry.
(8, 9)
Staff need to be trained to the level already described. They need

(8, 9)
Staff need to be trained to the level already described. They need 
good leadership ability, capabilities in organizing group activities, and a good understanding of psychopathology. Beyond these requirements, therapeutic goals will involve major changes in per-sonality and social functioning involving the uncovering and 
exploration of unconscious dynamics. So staff will need access to a

1353
range of specialized training opportunities which should provide 
psychodynamic theory, clinical supervision and, ideally, some opportunity for the practitioners’ own personal development.
The contemporary ﬁ  eld and its history
The paradigm shift that led to a vision of the group as a whole 
began over a period of time and in a number of locations. Trigant Burrow coined the term group analysis in the USA in the 1920s.
(10,11) Further development in the years after World War II 
period enabled workers to recognize the dynamics of groups and institutions and led to group and family therapy, milieu therapy, and therapeutic community concept and practice.
Second World War
In Britain and the US, during the Second World War, an apprecia-tion of group psychology led to a wide range of innovations, the most important of which included:
◆ The use of group methods for selection and allocation of work 
responsibilities
◆ Studies of group morale

◆ The integration of psychiatric knowledge to the management of 
large groups through the role of the command psychiatrist
◆ The treatment of acute and prolonged battle stress and the reha-
bilitation of returned prisoners of war.
Clinicians used the opportunities created within army psychiatry 
to apply methods developed in the pre-war years.(12) Brigadier J.R. 
Rees, Director of the Tavistock Clinic in the 1930s, largely created this opportunity in the British Army. His Tavistock colleagues formed an ‘invisible college’ and were responsible for signal achieve-ments in the advances in selection and treatment.
(13)
Foremost amongst these were Northﬁ  eld, the military hospital 
near Birmingham where S.H. Foulkes was a senior medical ofﬁ  cer.(14)
A refugee from Nazi Germany, Foulkes brought with him from the

A refugee from Nazi Germany, Foulkes brought with him from the 
Frankfurt Institute the revised understanding of Freudian theory that was also to prove inﬂ  uential in the US. In the New School for 
Social Research, New Y ork, and in the work of Neo-Freudians like Erich Fromm, Frieda Fromm-Reichman, and social theorists like 
Adorno, Marcuse, and Norbert Elias, psychoanalysis and Marxist theory were brought into a new, creative relationship.
(15) In the 
United Kingdom Foulkes ﬁ  rst developed his approach to group ther-
apy in Exeter before the war and was able to apply it successfully on a 
large scale to the treatment of war neuroses at Northﬁ  eld.
Post-war period
Group psychotherapy moved from inspirational and didactic models 
to psychodynamic and analytic ones in the post-war period.
(a) United Kingdom

The Group-Analytic Tradition: Foulkes gathered around him a small group of clinicians and others who developed his ideas and practises. Drawing on the ideas of Trigant Burrow, they called it group analysis and later established the Group-Analytic Society, and trained generations of clinicians. His ﬁ  rst book written in the heat 
of the Northﬁ  eld experience outlined the basics of his approach.
(16)
Other publications followed and, with Malcolm Pines, training 
courses were established which lead to the founding of the Institutes of Group Analysis and Family Therapy, the Association of Family Therapists, and Association of Therapeutic Communities. There are now training courses in group analysis in many centres in the United Kingdom and continental Europe. The Journal, Group Analysis ,

established by Foulkes, continues to be the major publication in European group psychotherapy. Group-analytic psychotherapy has undergone clinical evaluation by a number of clinicians.
(17–19)
The ‘Tavistock’ Approach: The approach originates in the work 
of Bion, Ezriel, Sutherland, and their colleagues. It shares with group analysis an interest in the underlying pattern of object relations in groups but, under the inﬂ  uence of Bion—its major 
exponent—his ‘basic assumption theory’ is applied to the exclusion of almost everything else. (Bion’s monograph was his only publication on groups and marked the end of his interest in the subject.
(20)) The approach has been especially inﬂ  uential in 
staff training and consultancy which, given the slender theoretical foundations on which it rests, suggests a wide responsiveness in the ﬁ  eld of basic assumption theory. The approach has undergone 
further development in the United States where it is often referred

further development in the United States where it is often referred 
to as group-as-a-whole. When employed as a therapy, it can over-look the individuality of a group’s members, disturbing some patients whose experience of the group situation can repeat early developmental traumas of neglect and misunderstanding by care-takers. Malan’s study of effectiveness
(21) raised serious questions 
about the model’s efﬁ  cacy in its clinical applications but its training 
applications continue to inﬂ  uence the ﬁ  eld.
(b) United States
(i) Early pioneers
Jacob Moreno  was the innovator of group psychodrama, a pioneer 
form of group psychotherapy.(22) He also introduced sociometry, 
a scientiﬁ  c method for the study of group afﬁ  liations and conﬂ  icts, 
widely accepted and used by social psychologists. Slavson  was 
an educationalist of psychoanalytic persuasion who became the central ﬁ  gure in the early development of group psychotherapy.

an educationalist of psychoanalytic persuasion who became the central ﬁ  gure in the early development of group psychotherapy. 
His clinical inﬂ  uence, particularly with groups for the parents of 
children in difﬁ  culty, and his focus on the dynamics of projection 
in groups has been of lasting importance.
(23) His organizational 
efforts lead to the formation of the American Group Psychotherapy Table 6.3.6.1  Organizing principles for group therapy
 1 Members will have been chosen by the therapist.
 2 They will have chosen to join and participate. 3 They will be expected to justify their place by reliable attendance and 
participation.
 4 The work will be governed by a psychotherapeutic contract. 5 The contract will include deﬁ  nitions of conﬁ  dentiality and other 
boundaries.
 6 A therapeutic alliance with individual members will be established

 6 A therapeutic alliance with individual members will be established 
either prior to their joining the group or during the early stages of their attendance in the group.
 7 Agreed parameters will include the duration and time-boundaries of the 
group as well as its membership and composition.
 8 Groups can be homogeneous or heterogeneous. 9 Groups may have a ﬁ  xed time limit or continue on a slow–open basis for 
many years.
10 Groups may have a stable and ﬁ  xed, or a rotating membership with empty 
places taken by new members.6.3.6 group methods in adult psychiatry

SECTION 6  treatment methods in psychiatry 1354
Association. Emanuel Schwartz  began to apply psychoanalytic 
ideas to group psychotherapy in the late 1930s and was later joined by Alexander Wolf .
(24, 25) In their approach, people under-
went an individual psychotherapy in the setting of a group, a kind 
of parallel process alongside their fellow patients, with attention focused on the transferential relationship between each individual and their therapist. The approach has been of lasting importance in creating a clinical framework for combining individual and group therapy. Foulkes’ criticism at the time was that the approach over-looked any systematic use of group-speciﬁ  c process. In contrast to 
their ‘psychotherapy in the group’ he offered group analysis as a clinical alternative, describing it as ‘psychotherapy by the group’ .
(ii) Irving Yalom
Y alom’s interpersonal approach is inﬂ  uenced by the interpersonal 
psychotherapy of Sullivan and Frank. His Theory And Practice of

psychotherapy of Sullivan and Frank. His Theory And Practice of 
Group Psychotherapy,  now in its ﬁ  fth edition and written jointly 
with Leszcz, is the ﬁ  rst systematic account of groups informed by 
research and remains one of the most inﬂ  uential books in the 
field.(3) Y alom’s later text on inpatient group psychotherapy 
systematized group work in that setting.(26)
(iii) The contemporary ﬁ  eld
There are many centres of excellence, a wide range of methods and models and an empirical base grounded in research. The most use-ful single text is by Rutan and Stone, now in its fourth edition.
(27)
Collections by Kaplan and Sadock(28) and by Alonso and Swiller(29)
cover the ﬁ  eld. Psychoanalytic models have a rich diversity of theory 
with contributions from object relations, self psychology, and social systems theory.
(30) The Modern Group movement is amongst the

(30) The Modern Group movement is amongst the 
most innovative, beginning with a classic text by Spotnitz(31) and 
developing through an active training programme, a journal, The
Modern Group,  and publications by Ormont(32) and others.
(iv) South America
There is a vigorous ﬁ  eld of development throughout South America 
that draws on both the Tavistock and Group Analytic traditions but is informed by independent sources based largely on the work of Pichon-Riviere. Tubert-Oklander and Hernandez de Tubert have introduced this approach, referred to as Operative Groups, to the English-speaking world.
(33)
(v) Continental Europe
Group methods have played an active part in the reconstruction of mental health services throughout Europe in the post-war period. Distinctive approaches are emerging. Those in Germany include psychosomatic practice
(34) and the Gottingen model.(35) The jour-

nal of the Heidelberg Institute of Group Analysis gives access to a vigorous ﬁ  eld. A major research study is in process, based in 
Germany, in which therapists throughout Europe are taking part and which aims to provide a detailed evaluation of group therapy, its patients, and its therapists.
(36) Other distinctive developments 
include those in Italy(43) and original training models, for example, 
those in Greece(37) and Norway.(38)
Principal models of psychodynamic 
group therapy
The therapist
The therapist is responsible to the group— and to the institution 
in which it is set—for achieving and maintaining professional competence and should have a level of training appropriate to the 
task. A formal qualiﬁ  cation in psychotherapy is the ideal training.

task. A formal qualiﬁ  cation in psychotherapy is the ideal training. 
This will have included theory, personal therapy for the therapist, and clinical supervision. Mental health professionals from all disci-plines make an active contribution to a rich and diverse service with the training requirements of theory and supervision arranged at their workplace. The opportunity to run a group is provided in most psychiatric and psychology training programmes. Many centres and training institutions offer training in group methods and several are wholly committed to the training of group thera-pists who have their own professional associations in the UK and internationally. Private once- or twice-weekly analytic groups are now regarded by many mental health professionals as the therapy of choice for their personal development. Other requirements for a

good therapist are listed in table 6.3.6.2.
(a) Making a beginning
The establishment of a group begins as a management task in the 
deﬁ nition of its goals, recruitment of its members, protection of its 
setting, venue and timetable, and in the maintenance of its ongoing life. It evolves as a therapeutic task in which the therapist is respon-sible for maintaining a therapeutic attitude to the individual mem-bers and to the group as a whole. Powerful affects and attitudes will be directed towards her which she will monitor and transform into verbal and non-verbal therapeutic responses.
The therapeutic rationale will allow the therapist to be discrimi nat-
ing and consistent about interventions of various kinds during the life of the group and what follows below provides an orientation— based on the dynamic elements of structure, process and content— to the three main models used in the UK.
Structure, process, and content: the dynamic elements 
of a group

of a group
Regardless of the therapist’s method, people usually start in groups 
with a form of serial monologue. Out of this arise the capacities to talk and listen that are often undeveloped or even non-existent at the outset of therapy but which are its core constituents. From talk-ing and listening comes self-disclosure and out of this social exchange identiﬁ  cation emerges, which in due course leads to 
dialogue and differentiation. So the conductor must give a place to monologue whilst, at the same time, cultivating dialogue—the exchange between members or sub-groups—and, ultimately, 
Table 6.3.6.2  Requirements for therapeutic competence
Requirements for therapeutic competence include:
1 The ability to follow complex interactions and processes.
2 The ability to discriminate between appropriate activity and a containing 
form of silence.
3 A reﬂ  ective attitude and the capacity to consider and reﬂ  ect upon the

3 A reﬂ  ective attitude and the capacity to consider and reﬂ  ect upon the 
processes concerning both the individual members and the group as a whole.
4 An eye for both the visible and invisible group and a curiosity about the 
unconscious or otherwise hidden aspects of a group’s life. This will require 
the therapist’s access to their own internal process and a capacity to make 
use of it.
5 A therapeutic rationale for action related to the group tasks and leadership 
requirements including the psychopathology of the individuals, their psychodynamics, and group dynamics.

1355
promoting discourse, deﬁ  ned here as the free interaction of partici-
pants in the ﬂ  exible and complex exchange that distinguishes the 
communication of a group.
Structure describes the more enduring aspects of any group’s 
makeup, the ‘architecture’ of its interpersonal relations conceptual-
ized ﬁ  rst in terms of the setting and its boundaries and then con-
ceptualized in the bond between each individual, the therapist(s), 
and the group as a whole. Process describes the ﬂ  uid and dynamic 
ﬂ uctuations of emotion and experience, the business of relating 
and communicating, the changes of association and inter-member 
responses. The content of a group’s exchange is in its visible and 
audible events, in the narrative line and dramatic content of peoples’ 
encounters, the topics raised, their thematic development, and the 
extent to which they are explored or avoided.
As Fig. 6.3.6.2 illustrates, each of these three dynamic elements

As Fig. 6.3.6.2 illustrates, each of these three dynamic elements 
has a determining inﬂ  uence on each of the others. For example, 
a group in which there was a problem caused by the institution’s 
failure to honour its commitment to reliable space for regular 
meetings, would have a serious structural problem. Intrusion, 
relocation, or a conﬂ  ict over space might then emerge in the con-
tent of the members’ associations as they talked about shared past 
experience. The therapist would need to decide whether to direct 
the process towards the connection between past and present anxi-
eties, or reassurance that the therapist would—from now on—be 
able to protect their space.
(a)  Overview of the Interpersonal, Tavistock, and 
Group-Analytic Models
In the Interpersonal school, intra-group interactions, including

In the Interpersonal school, intra-group interactions, including 
those between its members and the leader, are taken in their totali-
ty, but differentiating the leader as a different ‘sort’ of person from 
the others. In the Tavistock model, a two-body psychology is used 
to analyse the interchange between the leader and the group taken 
as a whole. The therapist’s principal role is in the analysis and 
interpretation of defences against primitive anxieties (or basic 
assumptions). The Group-Analytic Model calls on elements of 
both foregoing models. Like the Tavistock model it considers the 
leader as structurally different to other group members but like the 
Interpersonal model, it encourages the leader to work in the group 
with individuals. A three-body psychology is used to understand

with individuals. A three-body psychology is used to understand 
the role of the leader who is referred to here as the conductor. Therapy proceeds through the dynamic interaction between each 
individual, the conductor, and the group as a whole.
(b) The model of interpersonal group therapy
The focus is on interpersonal learning as a primary mechanism of 
change. The group provides the antidote to maladaptive interper-
sonal beliefs and behaviours through feedback from others and 
encouragement to experiment with healthier behaviours first 
within the group and then outside. The joint examination of intra-
group transference reactions allows members to replace processes 
that have a historical origin in the ‘there and then’ , the dynamic 
past, with those more appropriate to the ‘here and now’ , the 
dynamic present. The approach emphasizes the educational oppor-

tunities of working in the ‘here and now’ of the group. The therapist 
takes the responsibility for leading the group towards awareness of 
these interpersonal dynamics and their expressions. There is also 
greater therapist transparency than in other psychodynamic 
approaches with the therapist modelling desired behaviours, shar-
ing the reactions to events in the group directly, and being open to 
feedback from other group members.
As the diagram indicates, interpersonal dynamics are kept at 
the forefront of members’ attention by the therapist. This sets 
a pattern in which the content of members’ discussions and the 
process of their interactions gives the group its agenda. The inter-
personal approach places the therapist amongst other members

personal approach places the therapist amongst other members 
of the group without giving him a distinctive structural identity 
and omits any formal demarcation for the boundaries of the group 
as a whole.
The model provided the early descriptive research on the phases 
of small groups, on the basis of which Y alom tabulated the curative 
factors  in a group’s life (see Table 6.3.6.3).
This construction has been very inﬂ  uential. Y alom’s use of the 
term ‘curative’ poses many problems for those clinicians who see 
the goals of therapy involving personal growth and change. He did 
much to address this difﬁ  culty by singling out the last of his ‘cura-
tive’ factors—existential issues—for special treatment in a subse-
quent text.(49)
(c) The Tavistock model
Bion’s ideas have an explanatory power and simplicity of applica-

tion that continues to prove illuminating.(40) In a group at any 
Fig. 6.3.6.2 The dynamic elements of a group.MEMBER
MEMBER
MEMBER
MEMBERMEMBERTHERAPISTMEMBER
Fig. 6.3.6.3 The elements of an interpersonal group.6.3.6 group methods in adult psychiatry

SECTION 6  treatment methods in psychiatry 1356
point in time, its culture and climate are governed by primitive, 
unconscious anxieties that impede its capacities for rational work in which the person or representation of the leader plays a crucial part. The anxieties, organized into one of three categories, referred to as basic assumptions , are dependency, ﬁ  ght or ﬂ  ight, and 
pairing. They affect the group as a whole in which only one basic assumption is believed to be operative at any point in time. Bion saw basic assumptions as interfering with the ‘work group’ , the more rational, higher-level functioning of the group and its mem-bers. The therapist’s key task lies in understanding and interpreting the operative basic assumption to the whole group. The meaning of individuals’ experience is subsumed by this understanding of the whole. This therapist-centred approach sees transference only as directed towards the therapist who represents authority. In depen-

dency , the group tries to elicit protection through passive or depen-
dent behaviour. In ﬁ ght/ﬂ  ight  they will attack the therapist or 
some other issue; or retreat and withdraw. And in pairing  they may 
create a group illusion that some magical form of rescue may arise from the dilemmas of group life through charged partnerships. Hopper has introduced a fourth basic assumption that he calls massiﬁ  cation/aggregation  in which the defensive structures of 
groups or societies in crisis is thought to entail either a rigid fusion of identities excluding individuality, or extensive withdrawal 
preventing mutuality.
The two-body psychology used here enforces a series of clinical

The two-body psychology used here enforces a series of clinical 
constraints that reduce the complexity of group interaction to a bi-personal exchange between therapist and group taken as a whole. As Fig. 6.3.6.4 illustrates, intra-group dynamics are considered only in their entirety for what they reveal about the unconscious state of the group as a whole, and for what they indicate about the nature of the group’s relationship with the therapist. Figure 6.3.6.4 illus-trates how the therapist stands outside the group in a stance that is not only neutral and dispassionate but also opaque and with-holding of self.
Ezriel, basing his work on Bion, developed his theory of com-
mon group tension .
(41) He believed that the group would be caught 
up at any given time in a commonly shared conﬂ  ict centred on the 
unconscious fear of catastrophe, what he called the dreaded state .

People would avoid a state in the group—say one in which they talked about sad feelings—because of the unconscious fear that talking about sadness would lead to a dreaded state, in this case a depressive collapse. A group would be driven into unconscious, defensive organization—what he called the required state —to 
keep sadness at bay. For example, an extended period of manic humour, the required state, would help prevent the avoided state ,
sadness, and this would in turn protect against the dreaded state.Interpretations would allow members to become increasingly aware of the underlying catastrophic fears and reduce their need for defensive organization.
Horwitz calls Ezriel’s approach ‘deductive’ , in that it relates

Horwitz calls Ezriel’s approach ‘deductive’ , in that it relates 
individual’s contributions only to the common group tension. He realized that this deductive approach was clinically unproductive and developed, what he called an ‘inductive’ method which is group-centred.
(42) Interventions are ﬁ  rst addressed to individual 
members in the group. Only after working with patients individu-ally does the therapist introduce a common theme that binds them together. Thus the therapist, as in the Group-Analytic model, works on a ﬁ  gure/ground basis in which individual contributions are 
valued and explored in their own right before they are contextual-ized in the life of the group as a whole.Table 6.3.6.3  Yalom’s curative factors
 1 Instillation of hope
 2 Universality 3 Imparting information
 4 Altruism
 5 Corrective recapitulation of primary family group
 6 Development of socializing techniques
 7 Imitative behaviour 8 Interpersonal learning
 9 Group cohesiveness

4 Altruism
 10 Catharsis 11 Existential factors
Fig. 6.3.6.4 The elements of a 
Tavistock group.MEMBER
MEMBER
MEMBER
MEMBERMEMBERTHERAPIST
MEMBERTHERAPY GOVERNED BY
2-PERSON RELATIONSHIPBETWEEN THERAPIST &
GROUP AS A WHOLE,
OFTEN DISTORTED BYBASIC ASSUMPTIONSBOUNDARY OFGROUP AS AWHOLE

1357
Another approach, focal conﬂ  ict theory , as developed by Whitaker 
and Lieberman(43) is similar to Ezriel’s in focussing the therapist on a 
conﬂ ict that becomes his point of emphasis, but it answers Horwitz’s 
criticisms. On their account, underlying disturbing motives
in group behaviour are acted against by unconscious, restrictive 
solutions . On their account the therapist—by focusing on such key 
conﬂ  icts—helps give members access to the unconscious anxieties 
and once these have been relieved they can construct more enabling 
solutions  to the shared dilemmas of the group. The idea of focal 
conﬂ icts, conceived of in these broader terms, has become an integral 
part of the Group-Analytic model.
(d) The Group-Analytic model

This approach integrates important aspects of the two preceding models but introduces a number of new elements. As Fig. 6.3.6.5 suggests, the therapist is encouraged to address the individual as well as the whole group and considers the more conscious and individual dynamics as well as the unconscious and potentially destructive whole-group dynamics. The approach is guided by an integrated set of concepts relating structure, process, and content to one another in which the group conductor works both as thera-pist and as group member to foster and cultivate the ordinary lan-guage of shared conversational experience. He will at times take up the position of the group’s manager, and at other times he will speak personally as one of its members. Groups may begin with a relatively high level of leadership activity, referred to as dynamic

administration , which is ﬂ  exibly reduced with a decrescendo of 
responsibility as the group becomes the therapist and the leader-
ship function is devolved upon its membership who becomes active 
co-therapists in each other’s treatment
(44). Figure 6.3.6.6 indicates 
how, in this approach, at one key moment in the group its theme can focus on structural dynamics that link one member to both the 
therapist and to the group as a whole. The web of interconnecting dynamics between any one member and all the others, is summa-rized by ‘the group as a whole’ , and this is called on to represent the inter-connecting latticework of relationships that includes all the members and the therapist.(c) The Matrix
As Fig. 6.3.6.6 indicates, the conductor is inside and a part of the group, the structural elements of which provide a way of under-standing the crucial links between each member, the conductor and the group as a whole. The triangle by which the group’s psy-

chological objects are linked to each other illustrates one of the 
6 corresponding patterns of connection. When replicated for each of the 6 members, the diagram will produce a matrix  of relational 
patterns, a complex relational ﬁ  eld that will undergo change in 
terms of alliances, sub-groups, and polarizations. This concept of the matrix is crucial in group analytic theory. It allows us to accept that all events in a group will become part of an unconscious net-work that is intrapsychic, interpersonal, and transpersonal. The developing matrix creates the capacity to receive, contain, and eventually transform individuals’ contributions, fostering integra-tion at the individual level as it does so in the group as a whole.
Free-ﬂ  oating discussion: Free ﬂ  oating discussion is the group-

analytic equivalent of free-association. The term originates in Foulkes’ own writing and describes a set of key clinical concepts in therapeutic practice that distinguish the group-analytic approach. The language of the group is discussed in the dynamic life of groups, below.
Group-speciﬁ  c process: These processes, also mapped out origi-
nally by Foulkes, have been studied further by Pines
(45) and by 
Agazarian and Peters.(46) The key concept of resonance  describes the 
unconscious communication of emotion. The group provides its members with a wide ﬁ  eld of meaning which is explored as they 
mirror  one another’s experience, ﬁ  nd their emotions ampliﬁ  ed by 
association with one another, and ﬁ  nd condensed , sometimes highly 
aroused, cathartic experience, moments charged with signiﬁ  cance.
Content analysis: Foulkes described four levels at which the

Content analysis: Foulkes described four levels at which the 
content of the group’s discussion can be analysed in the search for meaning.
(47) In the Tavistock model this is the therapist’s exclusive 
task, whereas here interpretation is only one amongst a number of others. The therapist’s overall stance is to foster communication and educate the group’s members about the dynamic links between the group’s structure, the content of the discussion, and the form 
Fig. 6.3.6.5 Group Analytic 
psychotherapy.1: Group activity *  Psychotherapy in the group, by the group, including the conductor
2: Group conductor *  As therapist
*As group member 
3: Group matrix *  The ordinary language of shared conversational experience in
which people struggle with meaning 
4: The dynamic elements of a group:
structure

structure
process content6.3.6 group methods in adult psychiatry

SECTION 6  treatment methods in psychiatry 1358
in which it takes place. Figure 6.3.6.7 illustrates the conductor’s 
therapeutic role in relation to each of these dynamic elements of the discussion.
(f) Recent developments in group-analytic psychotherapy
The role of dreams in group psychotherapy has been reconsidered.(48)
Friedman described two of the unconscious functions they serve in group therapy—requests for containment and inﬂ  uence on 
relations with the dream audience.
(49) Lipgar and Pines(50) work 
towards an integration of the ideas and methods of Bion and Foulkes with discussion from an international panel. Nitsun
(51)
considers sexuality in group psychotherapy: sexual identity, bound-ary transgression, erotic connection, dissociation of desire, the group as witness, erotic transference and counter-transference, and the effectiveness of psychotherapy.
(g) The conductor as therapist and group member

At times of coherence, when the members are close in the shared experience of a moment, or when there is an issue charged with meaning, the group-analytic approach comes into its own. The symbolic content of the discourse might evolve in the language content, the ﬂ  ux of interactions, or the attention given to an indi-
vidual’s problems. The conductor needs to be able to model this use of imaginative play—with images, associations, or exchanges—and then stand back to allow members to take the enquiry forward. Cox
(52) shows how images can safely hold experience too painful 
or brittle to tolerate much analysis. People discover that images can touch the depths before they stir the surface, giving access to profoundly felt and deeply hidden concerns. When used and played 
with in this way, the mutative use of metaphor  provides the whole

with in this way, the mutative use of metaphor  provides the whole 
group with a vehicle for change. Other aspects of the therapist’s activity are summarized in Table 6.3.6.4.
The dynamic life of groups
In the sections that follow we draw on our own Group-Analytic model to examine a range of clinical considerations and make them as relevant as possible to the widest range of practitioners, regard-less of their own models.
Group development theory
Many schemata have been proposed, usually derived from time-limited experiential and study groups but some of these can provide a useful orientation. Bennis and Shepard,
(53) followed by 
Y alom, write about the initial stages of orientation , involving a 
search for structure and goals, dependence on the leader, and concern with boundaries. Their second stage is characterized by conﬂ  ict, particularly over norms , authority, and control. Their 
third stage is achieved with a high level of group coherence  that

third stage is achieved with a high level of group coherence  that 
allows for inter- and intra-personal exploration. They acknowledge that the boundaries between phases are not clear and that a group never graduates permanently from any one phase.
In slow open groups, especially, this idea of discrete phases has 
its limits. The group-analytic approach provides a cyclic model in which focal issues such as affection, intimacy, personal history, and change, are understood and struggled with repeatedly. A group Fig. 6.3.6.6 The elements of a group-analytic theory.BOUNDARY OF
THE GROUP AS AWHOLE
THERAPISTmember
member
member
membermember
memberFIGURE GROUND DYNAMICS
ALLOW ANY THEMATIC FOCUS TO
BE FIGURAL.  HERE THE
STRUCTURAL DYNAMICS FORONE PERSON ARE FIGURAL, THE
OTHERS SERVING AS
BACKGROUND
TRIANGULATION BETWEEN
EACH MEMBER, THE
CONDUCTOR & THE GROUP ASA WHOLE, GIVES THEMATIC
FOCUS TO THE MATRIX STRUCTURAL
DYNAMICS RELATETHIS MEMBER TO
THERAPIST & TO
GROUP AS A WHOLE

1359
understands in these terms struggles with developmental tasks
rather than phases, in the course of which it is the individuals who enjoy growth, differentiation, and progressive change.
(a) Developmental stages and thematic focus
Figure 6.3.6.8 provides a map of these developmental tasks con-ceived of in logical rather than sequential terms. The way in which one person comes into the group will be different to the arrival of another. The terms on which one person joins will have a deter-mining inﬂ  uence on each of the stages they pass through. For 
example, preoccupations about how someone came into the group—the terms of their engagement—might be resolved only when the person leaves perhaps one, three, or ﬁ  ve years later, when

example, preoccupations about how someone came into the group—the terms of their engagement—might be resolved only when the person leaves perhaps one, three, or ﬁ  ve years later, when 
they have to assess the outlook for their future as they look back over the years spent in therapy. So the diagram can be used as a thematic map for one person’s journey through therapy, or as a way of appraising the stage reached by the group as a whole.
Early stages are dominated by the anxiety of being involved in 
a new situation and by questions about other group members. Preoccupations are likely about boundary issues, conﬁ  dentiality 
and security. In the second stage, those familiar with psycho-
therapy—or otherwise accustomed to talking about themselves—will be at an advantage. There will be a range of tensions about group norms and disclosures, reasons for joining and discrepant levels of conﬁ  dence about using the group. In the third stage,

members will defend against intimacy with one another and strug-gle with questions of trust, attachment, and afﬁ  liations. In the DYNAMIC ELEMENTS
………………………………………………………....……...
A: Structure
Individual
Conductor
…………………………………………………………….......
B: Process
Amplification
Resonance Mirroring
Condensation
,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
C: Content
The shared experience of the group analysed at 4
levels :
1 Current level
2 Transference level3 Projective level
4 Primordial or archaic levelCONDUCTOR’S THERAPEUTIC ROLE
……………………...…………………………..
A: Dynamic administration
1 Group selection and composition
2 Managing the setting
3 Managing boundaries, membership
 and time issues 
…………………………...……………………..
…………………………...……………………..B: Facilitate members’ participation
and reflective analysis
1 Allow and cultivate free-floating
 discussion
2 Location of group preoccupations
 and focal conflicts
3 Translation from language of

 unconscious symptoms to conscious behaviour – “ego
 training in action” 
C: Analysis and interpretation
The conductor working as both therapist
and group member :
1 Therapist provides holding,
 containment and reflection
2 Analysis of transference issues3 Interpretation and therapist’s use  
 Of counter-transference 
4 Mutative use of metaphor and
 allegoryGroup-
as-a-
whole
Fig. 6.3.6.7 Structure, process, 
and content—the conductor’s therapeutic map.
Table 6.3.6.4  The therapist’s activity
A: Leadership and analysis
 1 Model a capacity for open, direct communication
 2 Maintain therapeutic neutrality
 3 Attend to boundary events 4 Provide holding and containment
 5 Withhold personal material
 6 Drawn on counter-transference for 7 Reﬂ  ection on group events
 8 Bring events from background to foreground, or vice versa

5 Withhold personal material
 9 Provide linking communications10 Clariﬁ  cation and confrontation with individuals
11 Attention to omissions, avoidance, denial
12 Maintain silence
B: Interpretation
1 Locate group preoccupations
2 Translate from the language of unconscious (individual and group) 
behaviour
3 Interpret or provide metaphorical constructions for
I  Defences and resistancesII  Transference and projective process
III Archaic and primordial experience6.3.6 group methods in adult psychiatry

SECTION 6  treatment methods in psychiatry 1360
fourth stage, as members become increasingly able to trust the 
group with self-disclosure, observed changes might become mani-fest as self-exploration yields the beneﬁ  cial experience of individu-
ation and differentiation. In the concluding stage, people prepare for departure and ﬁ  nd themselves comparing points of difference 
between changes achieved in the group and the state of their lives outside—generalising from the arena of therapy to that of real life. Has therapy made a lasting difference? Will it be maintained outside?
The language of the group
Foulkes suggested that ‘symptoms, in themselves unsuitable for sharing, exert, for this very reason, an increasing pressure upon the individual to express them’ .
(54) The group equips the person to

(54) The group equips the person to 
transform the mute and inchoate language of symptoms into a socially understandable form of discourse. Following publication of Schlapobersky’s paper, The Language of the Group, there is increasing interest in characterizing group phases in terms of the language that predominates, using theory from discourse analysis and the Foulksian concept of free-ﬂ  oating discussion.
(16)
It is possible to differentiate between three primary forms of 
speech that arise in the matrix of any group. At the most basic level monologue— speaking alone (with or without an audience)—is a 
form of individual self-expression. At the next level dialogue —a

form of individual self-expression. At the next level dialogue —a 
conversation between two people—is the form of communication that distinguishes a bipersonal exchange. And at the third level discourse —the speech pattern of three or more people—allows 
the free interaction of all its participants in a ﬂ  exible and complex 
exchange that distinguishes the communication of a group. These patterns of speech are universal cultural forms arising in all com-munication and are present in the life of every group, although in no set order. Monologue can be understood as a soliloquy, dialogue as the resolution of opposites or the search for intimacy, and dis-course as the work of a chorus. The use of free-ﬂ  oating discussion 
allows a pattern of exchange to move freely between these different speech forms, each of which constitutes a distinctive type of

allows a pattern of exchange to move freely between these different speech forms, each of which constitutes a distinctive type of 
communication. It is through this movement—from monologue through dialogue to discourse and back again—that the group-analytic method comes into its own, creating an arena in which the dialectic between the psyche and the social world helps to refashion both.
(13,14)
The group analyst works as both group member and therapist, beginning with dynamic administration, assuming an active role in a new group and allowing a decrescendo  of his own role as the 
group gains authority. He is responsible for helping the group with the location  of disturbance in its process and for providing a 
balance between analytic and integrative forces whilst manifest content is translated into language that describes the unconscious. Transference is prominent but the work is undertaken in the dynamic present. Foulkes’ account in the following passage,
(55) of

(55) of 
the conductor at work in a group, stands in dramatic contrast to Freud’s account of the psychoanalyst at work behind the couch:
He treats the group as adults on an equal level to his own and exerts an important inﬂ  uence by his own example . . . representing and 
promoting reality, reason, tolerance, understanding, insight, catharsis, independence, frankness, and an open mind for new experiences. This happens by way of a living, corrective emotional experience.
Disturbed, narcissistic, or borderline patients bring to the group

Disturbed, narcissistic, or borderline patients bring to the group 
more primitive psychic structures and processes that put strain on the resources of other group members. Such patients can create turmoil in which the leader’s task is to maintain the group at a more mature level of psychic organization. By responding to part-object relationships and processes on the level of whole-object relations, containing responses can be established. Progressively, these help to build for the disturbed patient a more benign world of inner object relationships and processes. More disturbed patients desperately seek attention in ways that are inappropriate and disruptive. This search for attention  arises because the patient 
cannot establish a sense of connection  between herself and the 
processes of the group. Mirroring and resonance can steadily come to replace these isolated and fragmentary responses allowing the patient to attain—for the ﬁ  rst time—a coherent sense of self and

processes of the group. Mirroring and resonance can steadily come to replace these isolated and fragmentary responses allowing the patient to attain—for the ﬁ  rst time—a coherent sense of self and 
a capacity to recognize the identity of others.
(a) The dynamics of change
As noted above, Y alom cited 11 ‘curative’ factors responsible for change in groups. Foulkes believed there were four key group-speciﬁ  c 
factors: mirroring, exchange, social integration, and activation of the collective unconscious. Tschuschke and Dies
(56) have identiﬁ  ed 
ﬁ ve key factors that they could study empirically (Table 6.3.6.5).
(b) Binding forces: alliance, cohesion, and coherence
Group alliance  has as its major focus the quality of the relationship

Group alliance  has as its major focus the quality of the relationship 
that develops between each individual member and the therapist(s). These alliances grow as each individual develops a transference relationship to the therapist and can feel that their own particular individual dynamics are recognized. Group cohesion used to be compared to the concept of therapeutic alliance in individual psychotherapy but current research shows that alliance (deﬁ  ned as 
the affective bond that develops between each group member and the therapist) can be differentiated from group cohesion.
Group cohesion  describes the bonds between group members, their 
attitudes, and their commitment to therapeutic work, in particular 
Fig. 6.3.6.8 Developmental stages and thematic focus.STAGE 1 : ENGAGEMENT
IN/OUT
UP/DOWN
NEAR/
FAR
SAME/

IN/OUT
UP/DOWN
NEAR/
FAR
SAME/
DIFFERENTSINK/SWIMSTAGE 5 : TERMINATIONSTAGE 2 : AUTHORITY
STAGE 3 : INTIMACY
STAGE 4 : CHANGE

1361
their feelings of attraction and dependency. These processes are 
interdependent and in combination they provide optimal condi-
tions for positive group process and outcome.(57)
Group coherence  is a more evolved group state requiring but 
going beyond cohesion. It evolves as a semantic matrix, built on the earlier, relational matrix. When a group moves through support and understanding to be able to recognize and work through conﬂ  ict, it can achieve a sense of containment.
(58) At this stage the 
group becomes a more complex, self-evolving, and self-deﬁ  ning 
entity capable of reaching deeper levels of exploration, acceptance, and understanding.
(c) Corrective emotional experience
The concept was introduced by Alexander to describe the patient’s recognition of discrepancies between present and past experience. Grotjahn, a colleague of his, applied this to the group, describing it as ‘the corrective family experience’ .

There is a built-in correction of the transference phenomena through the peer relationship in groups. An analyst is trained to let the transference neurosis to grow to full bloom. Members of a group are neither trained nor willing to accept such projections . . . and will correct them. This is the basis of a corrective therapeutic family experience.
(59)
Oedipal, sibling, and pre-oedipal constellations are activated in 
group therapy and can be worked through as the members play parts in each other’s family scenarios.
(60) The task of the therapist 
interprets transference and helps the group as a whole to develop coherent norms of understanding and responsiveness that equip its members to go beyond the private preoccupations that might have brought them into therapy. Garland calls this taking the non-
problem seriously .
(61)
(d) Resonance, mirroring, and other dynamic processes
Foulkes described the group as ‘a hall of mirrors’ . Each person, he

(61)
Foulkes described the group as ‘a hall of mirrors’ . Each person, he 
thought, could see aspects of themselves reﬂ  ected in the personality 
and behaviour of others and could often more easily recognize these aspects of the self than by direct introspection. We cannot know ourselves in the absence of reﬂ  ective mirroring, the feedback 
and information we obtain from others according to our presence and behaviour in the group brings us to a greater awareness of who we are. Resonance in the group is the unconscious communication of emotion by which the other process dynamics—like mirroring, ampliﬁ  cation and condensation—are effected.Insight and outsight, regressive and progressive forces in groups
The dictum, ‘where id was, ego shall be’ , coined originally by Freud

The dictum, ‘where id was, ego shall be’ , coined originally by Freud 
to ground the psychoanalytic enterprise in an easily comprehensible principle, has been superseded for group workers by the idea of ego training in action , coined by Foulkes. It emphasizes two relat-
ed issues. The ﬁ  rst is that insight —the understanding of the self—
is related to outsight  deﬁ ned as the understanding of the other(s). 
And the second is that people ﬁ  nd growth and change as much 
in what they do for others— progressive behaviour —as in what 
others can do for them— regressive behaviour . So the group is 
designed to create an arena in which there is continuous ﬂ  ux 
between these different elements.
(e) Imitation, identiﬁ  cation, internalization, and differentiation
(i) Imitation
From early in infancy, we observe and copy what others do. A ther-

apeutic group is designed to create conditions in which imitative behaviour, or modelling, can be experienced, monitored, and understood. It brings the group members closer together and, as it develops into identification and internalization, it increases the cohesiveness of the group.
(ii) Identiﬁ  cation
Peoples’ predominant modes of relatedness to one another—such as compliance, avoidance, dominance, receptivity, exploita-tion, and need—become apparent in the group. The group exposes these patterns of relatedness to reveal how the internal objects with which members have identiﬁ  ed can be externalized and

encountered in the group through projection and introjection. Members compel each other to play and re-play the dramas of their interior lives and past injuries in the ‘here and now’ of group experience.
(iii) Internalization
Intimacy with others is developed through the exchange of under-standing. As it is given and received, it allows for new forms of inti-macy within the self. Constructive  experience in the group 
is taken in and becomes part of the self. This can allow the recogni-tion and reappraisal or deconstruction  of repetitive patterns 
and ﬁ  xed, maladaptive characteristics. And this can lead to the 
reconstruction  of the self in the concluding phases.
(iv) Differentiation
Over time people become aware of signiﬁ  cant differences in their 
reactions, emotions, and psychological structures. Examples are increased tolerance of affect, understanding and modiﬁ  cation of 
self-inﬂ  icted pain, diminution of guilt and shame, retrieval of

self-inﬂ  icted pain, diminution of guilt and shame, retrieval of 
lost aspects of the self, increased openness with others, increased spontaneity and creativity, and, most critically, feelings of tolerance for or forgiveness of the self, for the constraints into which it has 
been driven by past injury and present defence.
(62)
(f) Personal and group resistances
Some resistances are manifestations in the group of the characteristic

(62)
Some resistances are manifestations in the group of the characteristic 
defences of the members, evident in their interpersonal behaviour. Others are resistances of the group as a whole, shown in blockage of free-floating discussion, opposition to group interaction, sub-grouping, and opposition to the deepening and broadening of the group’s exploration. A constructive function of resistances should be kept in mind when monitoring the pace at which both individuals and the group can progress without experiencing Table 6.3.6.5  Five factors in the dynamics of change open to 
empirical evaluation
(56)
1 Cohesiveness Closely related to 2 & 3 as determining factors that 
inﬂ  uence outcome in 4 and 5
2 Self-disclosure Closely related to 1 & 3 as determining factors that 
3 Feedback Closely related to 1 & 2 as determining factors that 

4I n t e r p e r s o n a l  
learning outputEvidence of working through process seen in 4
5 Family 
re-enactmentFindings of change in these patterns provides evidence of 
enduring psychic change6.3.6 group methods in adult psychiatry

SECTION 6  treatment methods in psychiatry 1362
overwhelming anxiety. Resistances can protect people from fears of 
loss of self and identity; and from fears of engulfment through excessive intimacy. Resistances then become opportunities for understanding fear of change, for the re-working early develop-mental patterns, and for discovering the freedom that can follow release from excessive internal control.
(g) The anti-group
Nitsun developed an understanding of the anti-group, bringing together the work of Bion and Foulkes.
(63) He introduced the 
concept to help understand the negative experiences therapists face in periods of stagnation, hostile silence, severe conﬂ  ict in or

concept to help understand the negative experiences therapists face in periods of stagnation, hostile silence, severe conﬂ  ict in or 
premature departure from the group, or negative feelings about the work of the group. These situations can arise when the group recapitulates early experiences of loss, deprivation, anger and envy or in an effort to avoid these emotions. Negative emotions can then be projected towards the group and the conductor who represent early care-givers. These feelings can be worked on when the thera-pist uses counter-transference to recognize and verbalize projected feelings. The idea of negative elaboration  (see below) is a useful 
guide in this process.
Basic clinical issues
Dynamic administration
(a) Selection and composition
Group composition is the therapist’s ﬁ  rst and most enduring

Group composition is the therapist’s ﬁ  rst and most enduring 
contribution to the group for its membership will determine the outcome of therapy. Preparing patients for treatment with several individual sessions or, if necessary, an extended programme of preparatory work will provide the therapist and patient with a basis for judgement about therapeutic prospects. Preparatory work has been found likely to enhance participation and reduce drop-out rates, although ﬁ  ndings are not conclusive.
(64)
The criteria for selection are exclusive rather than inclusive since

(64)
The criteria for selection are exclusive rather than inclusive since 
most patients seeking psychotherapy can be accommodated in a group, provided a suitable one is available. The selection process should take into account both the patient needs and the composi-tion of the group. A service should, ideally, provide a selection of groups into which people can be placed both according to their needs and characteristics, and those of the particular group. Selection criteria aim to optimize the ‘ﬁ  t’ between the needs and 
resources of the individual and those of the group.
Table 6.3.6.6 lists inclusion criteria, while Table 6.3.6.7 gives a 
shortlist of excluding criteria. Lists of this kind should be used with caution. In general, at least four inclusive criteria should be found amongst those to be included in outpatient, dynamic psychothera-py groups with a mixed population. If there are four exclusion cri-
teria, one should be very wary about including the person in a

teria, one should be very wary about including the person in a 
group. However, there are many exceptions.
The criteria in Tables 6.3.6.6 and 6.3.6.7 hold good for mixed 
groups and outpatient services generally. With homogeneous groups for special populations, the range of potential candidates is much wider, for example, Hearst describes a population of severely deprived mothers drawn entirely from those on the exclusion list.
(65)
(b) Homogeneous and heterogeneous groups
Homogeneous groups: Are for people with similar symptomatic or diagnostic pictures, such as phobias, anxiety, or depression. Such groups offer more immediate support to members, are better 
attended, and provide faster symptomatic relief. However they may remain at a more superﬁ  cial level with less interpersonal 
learning.
(67)
Homogeneous groups are also used for those with similar

learning.
(67)
Homogeneous groups are also used for those with similar 
personality structure or life-history, particularly those in socially extreme categories. For example, men with histories of sexual violence or women who have suffered rape or torture may be treated.
Heterogeneous groups: Melnick and Woods
(67) suggest that 
group composition should be guided by an optimal balance between conditions ensuring group maintenance or homogeneity, and those maximizing interpersonal learning or heterogeneity. A group which shares one strong characteristic—a diagnosis such as an eating disorder, or a personal attribute like intelligence—can accommodate a diversity of presenting problems or social back-grounds. If, on the other hand, the members are similar in social background, diversity can be incorporated on another basis, such as diagnosis. Thygesen

(68) found that diversity enabled group 
members to recognize and work with differences in mental and emotional attitudes, life histories, and developmental problems. Recognizing and working with difference develops emotional resources, promotes ﬂ  exibility, and the tolerance of emotional 
tension. And it encourages the group to move from cohesion , in 
which security is based on identiﬁ  cation, to coherence  in which 
relationships are based on differentiation.
It is useful also to identify members likely to be isolated from 
the rest of the group by age, ethnicity, gender, personality, or prob-lems or a history that noone else shares, for they are likely to ﬁ  nd Table 6.3.6.6  Inclusion criteria for psychodynamic groups (at least 
four of these criteria should be present, for someone to join a group)
 1 Motivation to address personal issues, to resolve problems

 2 Willingness to try and participate 3 Some experience of successful relationships in childhood or present 4 Some interest in exploring and understanding the self 5 Some capacity to talk, listen, and relate 7 Some interest in others 8 Some sense that being amongst others could be helpful 9 Some ability to sympathize or empathize with others’ needs and problems10 Some indication of future reliability in attendance
Table 6.3.6.7  Exclusion criteria for psychodynamic groups(66) 
(if four or more of these criteria are present, then questions should 
be raised about inclusion)
 1 Those in acute crisis

 2 Prior history of broken attendance in therapy 3 Major problems of self-disclosure 4 Major problems with reality testing, i.e. paranoid projections or psychosis 5 Pathological narcissism 6 Difﬁ  culties with intimacy generalized into personal distrust 7 Defences that rely excessively on denial and disassociation 8 Emotional unavailability
 9 Tendency to be verbally subdued or withdrawn
10 Tendency to be hostile and aggressive, verbally or otherwise

1363
the group experience threatening. We do not put a patient into a 
position of being isolated.
Managing the structure, setting, and time boundaries
(a) Optimal and sub-optimal size
The optimal number for small group psychotherapy, ranging from ﬁ ve to nine, is determined by practical considerations. A smaller 
number than this minimum is likely to have an active attendance of only two or three and will not necessarily generate the corporate energy to produce movement. A group larger than this will exceed the number that can be taken into one person’s conﬁ  dence in 
a face-to-face exchange.
Sub-optimal groups  can provide valuable therapy under good 
(69) Low and irregular attendance is often associated

(69) Low and irregular attendance is often associated 
with a problematic composition, particularly if there is a high proportion of members with character disorders and borderline features. Their inner sense of deprivation and loss can make the group seem unreliable and threatening which can be reinforced if the therapist is seen to be in difﬁ  culty. Therapists who can 
maintain an understanding attitude and positive commitment to the group’s future will usually ﬁ  nd the situation settles into 
a working nucleus of members that can then be built upon.
(b) Setting and time-boundaries
The therapist supplies, creates, and maintains the setting through-out the group’s life. This requires attention to such matters as meeting times, punctual beginnings and endings, conﬁ  dentiality, 
the predictable frequency of its meetings and breaks, and the general guarantee of a stable background.

Every aspect of the group’s life, including absences, departures, 
late attendance, and extra-group communication in terms of let-ters, phone calls, and messages, referred to generically as boundary 
events , are open for discussion. Boundary events are interpreted 
for the meaning they might hold for the life of the group as a whole. This is a task initiated by but not conﬁ  ned to the therapist. Also, the 
setting itself—to which each member is seen to contribute—comes to acquire a capacity to hold  the individual members and contain
their anxieties and insecurities. The issue of containment is of 
great importance, as is the discovery—by people who may have no

great importance, as is the discovery—by people who may have no 
belief in themselves as responsible members—that they can take responsibility for themselves and expect responsibility from others. The group is thus responsible not only for the nurture, acceptance, and security of its members, but also for their containment, the setting of limits and the maintenance of consistent authority. The therapist will often have to lead the way in modelling both roles for the group’s members.
Fostering therapeutic norms and a culture of enquiry
The therapist encourages the sharing of experience and helps to balance participation, recognition, and translation. The thrust of a group’s life is towards greater shared involvement and the expression of emotions. The expression of feeling may arise in the recounting of members’ life-situations and their reasons for therapy— narrative emotion —or it may arise in the interpersonal

encounters engendered by the telling—in the drama  of ‘here and 
now’ . Therapy becomes effective when the problems that brought the patient into treatment become recognizable in their interper-sonal encounters. At this point the affect lodged in the narrative will interact with the drama of the group’s current emotions, creating opportunities for corrective emotional experience. 
As the group progresses from constructive  to deconstructive ,
and ultimately to reconstructive , experience, it will encompass 
gesture, behaviour, body-language, and other non-verbal commu-nication, and actions that convey feelings when emotions have no 
words.
Guidelines for intervention
There are four modalities of time and place in any therapy group. 
The content of the exchange might be located in the past outside the group, the past inside the group, the present outside the group, and the present in the group.
Free-ﬂ  oating discussion will carry the focus of the exchange

Free-ﬂ  oating discussion will carry the focus of the exchange 
between these different modalities. The therapist’s task is to follow the interaction, to use interventions sparingly and strategically, to cultivate a reﬂ  ective curiosity for which Table 6.3.6.8 offers some 
pointers, and to work towards a progressive shift in the focus of attention, from no. 1, in Fig. 6.3.6.9 towards 4, via 2 and 3. A group governed by narrative in its free-ﬂ  oating discussion is likely to be 
dominated either by the the group’s own past or by the past of its members outside the group or by their current lives outside. A group governed by members’ intense experience of one another 
in the present, is likely to be governed by the drama of immediate

in the present, is likely to be governed by the drama of immediate 
encounter and understanding. The corrective recapitulation of early family life is likely to arise when the issues that predominate in no’s 1, 2, and 3, are translated into issues that prevail in 4, where they can be addressed in the present which allows new resolutions to be forged.
Groups for special populations
Nine distinctive clinical populations or approaches merit special mention. Some pose distinctive problems for group workers and, as we indicate in the section on borderline patients, they sometimes need co-therapists working together in the group.
Table 6.3.6.8  Interventions in time and place
 1 Address process rather than content
 2 Help members recognize aspects of themselves in others and accept the 
viewpoints of others on themselves
 3 Monitor the intensity of participation to allow an enabling pace so 
members can develop resources to deal with the intimacies of each others’ lives

 4 Establish a sense of enquiry about the ﬂ  uctuations of mood and outlook, 
and a sense of curiosity about thematic movement between the different 
modalities of time and place
 5 Help the group recognize role conﬁ  gurations taken up by individuals 
(therapist’s assistant or rival, joker, complainer)
 6 Hold in mind the gestalt of ﬁ  gure and ground. If someone stands out, 
what is the background against which they do so? If the ground changes 
the underlying pattern of the group, how might the ﬁ  gural person be 
affected?
 7 Help the group recognize sequences and patterns
 8 Help the group decode and ﬁ  nd meaning in the constructive, 
deconstructive, and reconstructive elements of its exchange

affected?
 9 Work towards the coherency of the group10 Foster the integration and integrity of its members6.3.6 group methods in adult psychiatry

SECTION 6  treatment methods in psychiatry 1364
Intensive outpatient psychotherapy heterogeneous 
groups for mixed populations
Group analytic psychotherapy has come into its own as a treatment 
modality in out-patient settings in the context of clinical agencies in public and private Health Services. Table 6.3.6.9 gives a picture of patients’ clinical needs in the private practice of John Schlapobersky over a twenty-year period. Some attempt has been made to indicate how these categories are mapped against those in ICD 10 and DSM IV . 
The medically ill
Groups have been used successfully for people with diseases of the cardiovascular, endocrine, gastro-intestinal, pulmonary, neurological, and renal systems. Amongst the applications are groups for those with renal dialysis and organ transplantation; chronic conditions such as diabetes, irritable-bowel syndrome, and rheumatic disease; and life-threatening conditions such as metastatic cancers.

Groups usually have members with a single disorder, last for 
20 sessions or fewer, and are psycho-educational in purpose. They emphasize compliance with treatment regimes and opportunities to share and explore the affective consequences of the conditions. The focus is on helping patients come to terms with the complaint; make changes in lifestyle, including diet, exercise, work, and recre-ation; deal with the inevitable anxieties about death, stigma, demoralisation, feared dependency, and loss of control; and resolve 
issues in relationships with loved ones and care staff. Clinicians 
write of how, despite their brevity, these groups provide a forum for sometimes profound exchange about major existential issues including pain, fear, and impending death.
(70)
Evaluation indicates such groups are effective in improving quality 
of life and, to some extent, in prolonging its duration even with meta-static cancer.
(71) Improved survival correlates significantly with

(71) Improved survival correlates significantly with 
enhanced, active coping. Spiegel reported a signiﬁ  cant, near-doubling 
of survival effects in 86 women with metastatic breast cancer treated for one year with weekly, supportive-expressive group therapy.
(72, 73)
The chronic mentally ill
In North American literature there are consistent ﬁ  ndings that 
schizophrenic patients do best in support groups that help them manage their symptoms and devise coping strategies for day-to-
day problems.(74) Group discussion is used to help overcome prob-
lems of social isolation, develop social skills and coping resources, and learn about maladaptive interactions evident in the ‘here and now’ of the group. The leader creates a sense of safety and security with supportive feedback. Areas that people ﬁ  nd helpful include

the management of symptoms, expression of emotion, and rela-tionships with others. Groups are less valued for acquiring insight or receiving guidance about the illness, medication, or economic problems. Interpretations that reveal or explore unconscious con-ﬂ icts, particularly transferential issues between members or with 
the therapist, are more likely to be harmful than helpful.
(75) Patients 
respond positively to an interactive, open, and safe group environ-ment, with gradually increased cohesion, decreased avoidance, and decreased conﬂ  ict.
(10)
Recently, Resnik(76) has described the use of insight-orientated 
psychotherapy with delusional problems using psychoanalytic principles in long-term group psychotherapy for psychotics.
Borderline personality disorders
Working with these patients can pose difﬁ  cult clinical problems

Working with these patients can pose difﬁ  cult clinical problems 
based on their ‘stable instability’ , including their inability to form a stable therapeutic alliance, mood oscillations, poor impulse con-trol, limited reﬂ  ective ability, painful states of psychic emptiness, 
followed by self destructive acting-out including self-destructive gestures and self-mutilation, violence; substance abuse, sexual act-ing out, and eating disorders. Some attempts at short-term group therapy combining cognitive behavioural approaches with the psy-chodynamic have shown promise. Longer therapies in out-patient groups have been encouraging but have not been evaluated. Good results are reported with in-patient applications at, for example, The Cassel and Henderson Hospitals, and in other forensic settings where day hospital group treatments are followed by outpatient group therapy in a carefully monitored programme.
(77)

(77)
Homogeneous outpatient groups do not do well because the 
members use similar ‘primitive’ defences of splitting, projection and denial, and have not acquired a stable sense of identity. They are suspicious of close interpersonal contact and have little capacity to care for or be cared for by others. Such groups lack cohesion, are pervaded by a sense of pessimism, hostility, rivalry, and easily fragment. Self-destructiveness is turned onto the group and its therapists who may experience intense counter-transference feelings of frustration, despair, and anger.
These problems can be managed in the containing setting of 
closed or specialized institutions. However, it is generally better to place one or two borderline patients in an otherwise well-functioning group where other members will not always respond to borderline pathology at the same primitive level. They may—like 
the adult carers of children—respond with understanding, ﬁ  nd

the adult carers of children—respond with understanding, ﬁ  nd 
ways of setting limits, and expect co-operation with the task at hand. After sometime, lengthy periods in which borderline patients maintain a frustrating presence on the margins of the group, or make themselves felt in aggravating terms at its very centre, they can acquire resources to take part in the group’s work in more mature terms. This combination of borderline and neurotic members in a carefully composed group can beneﬁ  t both parties. 
Borderline members will often have an unerring accuracy of perception about others, they can shake the group into more active interactions, and may not collude with others’ neurotic defences. Fig. 6.3.6.9 Location of group discourse in time and place.1 External past
2 External present3 Group past4 Dynamic present 
431
2

1365
The containing resources of the other members that set the norms 
and values of the group can slowly be internalized by the border-lines. As with many of these specialist areas, therapists working with these populations will need to acquaint themselves with the literature, have ongoing supervision and may—to begin with—work more fruitfully in co-therapy.
For a review of group psychotherapy for personality disorders 
see
(78, 79).
Forensic groups
Group therapy has been used for forensic populations, previously thought untreatable. Pioneering work has been done in the UK in special hospitals,
(80,81)  in prisons such as Grendon,(82) and great 
strides have been made in outpatient services at the Portman Clinic in London.
(83) Therapeutic community treatment for mentally dis-
ordered offenders in North America and Western Europe has been reviewed by Lees, Manning, and Rawlings.
(84)
The aim of forensic group therapy is to help patients ﬁ  nd words,

(84)
The aim of forensic group therapy is to help patients ﬁ  nd words, 
rather than actions, to express impulses and compulsions. A major part of the group’s work is to provide psychic space for perspective, negotiation, recognition, acceptance, and verbalization of hurt. Sharing the past and present can make it accessible as internalized, persecutory, and vengeful monologues are brought into dialogue.
In Britain, the Probation Service is the agency most actively 
involved in the groupwork with offenders.
(85) A report for the NHS 
Centre for Reviews and Dissemination (CRD Report 17) reviews studies of therapeutic communities and small groups and indicates that these show the most promising results of any form of treat-ment for anti-social personality disorders.
(86)Trauma
Group work with trauma victims is a comparatively new ﬁ  eld but

Group work with trauma victims is a comparatively new ﬁ  eld but 
one in which there is a vigorous range of applications. The most comprehensive overview is Van der Kolk’s text.
(87) There are groups 
for survivors of sexual abuse,(88) war trauma,(89) and torture and 
other forms of organized violence. Group work applications to traumatized children and adolescents is discussed in reference 90 and more generally in reference 91.
At the Medical Foundation for The Care of Victims of T orture in 
London, a group work programme caters for refugees and asylum-seekers. The groups provide psychotherapy for massive psychic and physical trauma, for problems of displacement and exile, and for trans-cultural problems.
(92) The diversity of different kinds of

(92) The diversity of different kinds of 
groups, including a range of activity, problem-solving, and psycho-dynamic groups, ensures that people can be provided with an envi-ronment in which they can each realize their own potential for self-healing. The programme is grounded in commitment to human rights, to team-work that addresses counter-transference issues, and to principles of positive intervention to counter emotions of hopelessness, and despair.
(93,94)
Couples groups
These groups cater for people in stable but troubled relationships in which there is some form of pernicious collusion. The approach can provide symptom relief and personality change in even severe difﬁ culties with relationships that last but do not work. Family 
therapy is concerned with the systemic function served by symptoms. Psychoanalysis is concerned with the origins of the Table 6.3.6.9  Categories of clinical need catered for by intensive, outpatient group therapy with mixed populations

(many of those who join groups are found in more than one of these categories of need)
1.  High dependency 
need including:2.  Problematic reactions 
to traumatic life 
events including:3.  Character 
problems 
including:4.  Serious 
relational 
problems 
including:5.  Selected people 
with borderline 
personality 
disorders 
including6.  Training of mental 
health professionals 
including:7.  Those seeking 
personal 
growth or understanding 
including:
a  Recovery from serious 
or enduring mental and physical illness
b  Help with the 
resolution of moderate psychiatric symptoms
c  Resolving addiction 
and substance abusea  Loss, injury, illness, 
disorder, infertility
b  Massive psychic and 
physical trauma
c  Adult sequelae of child 
sexual abusea  Immaturity and 
developmental problems
b  Chaotic life 
situations
c  Problems of 
identity and 
meaning
d  Problems of 
gender, sexuality, 
and orientation
e  Occupational 
problemsa  Intimacy 
avoidance
b  Recurrent

meaning
avoidance
b  Recurrent 
broken relationships
c  Intractable 
conﬂ  icts  Those with 
insight who 
both need and 
can tolerate containment  Psychotherapists, 
psychiatrists, 
psychologists, social 
workers, clergy  People who 
would have 
previously 
sought this 
through 
individual psychoanalysis
(John Schlapobersky: Group-Analytic Practice & Southwood Practice: 1987–2007) 
Category 1: Corresponds to Axis I in DSM IV and Groups F1–4 in ICD 10.Category 2: Corresponds to Axes III, IV, & V in DSM IV and Group F5 in ICD 10.
Category 3: Corresponds to Axes IV and V in DSM IV and Group F8 in ICD 10.
Category 4: Corresponds to Axis V in DSM IV and Group F8 in ICD 10.Category 5: Corresponds to Axis II in DSM IV and Group F6 in ICD 10.6.3.6 group methods in adult psychiatry

SECTION 6  treatment methods in psychiatry 1366
symptoms in object relationships. Group analysis provides a bridge 
between these paradigms, helping therapists ﬁ  nd a point of inter-
vention between marital and object relationships.
In a group, the process moves between the psychology of the 
individuals and the dynamics of their marriages. This interplay between the pair and the person—the interactive and historical dynamics—is part of the group’s free-ﬂ  oating discussion. The 
therapist uses this interplay, following the patterns of the group’s progress and making interpretations. Work is at times transferen-tial, other times, systemic techniques are used to address immedi-ate issues.
(95) Themes to which the group resonates are ampliﬁ  ed 
and members are helped to condense from this discourse, the kind of personal knowledge that promotes growth and change. There is insufﬁ  cient evaluation of the method’s efﬁ  cacy, but experience in

and members are helped to condense from this discourse, the kind of personal knowledge that promotes growth and change. There is insufﬁ  cient evaluation of the method’s efﬁ  cacy, but experience in 
hospital and private practice is very encouraging.
(96)
The elderly
This is an area of relatively new therapeutic exploration. A range of groups has been found useful in helping the aged to face their problems, improve their functioning, and feel happier about themselves. The groups include those offering support, activity, psycho-education, problem-solving, and insight, and takes place in many settings. Common themes include the ubiquity of loss, the acceptance of death, and the value of humour in lightening mood.
(97)
Brief therapy in groups

(97)
Spurred by economic and managerial pressures a distinctive modal-ity has evolved. Sessions are held weekly and number between 6 and 30. Characteristics that differentiate brief from long-term therapy include: clearly deﬁ  ned therapeutic goals agreed at the 
outset, the early establishment of a therapeutic alliance, active and ﬂ  exible therapeutic style, a focus on ‘here and now’ group 
process, the maintenance of time awareness, monitored in stage-speciﬁ  c terms, and the vigorous, directed exploration of thematic 
content.
Short-term groups may be homo- or heterogeneous. 
Homogenous groups have proved effective in helping patients deal with loss and grief, the consequences of trauma and abuse, and common problems coping with physical illness and disability. Heteregenous groups require more psychodynamic commonalities 
such as shared problems in inter-personal relationships, the ability 
to recognize and work on psychological issues, and the ability to

to recognize and work on psychological issues, and the ability to 
cope with the speed and intensity of the process. Those who lack psychological sophistication or are not motivated for self-
exploration, are not suited.
Research and evaluation
The general trends in literature show ample empirical conﬁ  rma-
tion that group treatments represent a powerful therapeutic inter-vention. A comprehensive overview of literature described positive outcomes with alcoholism, anxiety disorders, bereavement, buli-mia, depression, schizophrenia, and sexual abuse.
(98) There is also 
evidence of the adverse outcomes in group psychotherapy which can guide the clinicians training for the work.
(99)
(a) Outcome research
A meta-analysis of 58 controlled studies of psychotherapy for the treatment of depression showed that in comparison to a waiting list control the average treated patient was better off than 80 per

A meta-analysis of 58 controlled studies of psychotherapy for the treatment of depression showed that in comparison to a waiting list control the average treated patient was better off than 80 per 
cent of the controls.
(100) The efﬁ  cacy of group and individual therapy 
was almost identical. Tyllitski(101) also reported no appreciable 
difference between individual and group therapy effectiveness, 
both doing better than the control condition. Budman et al. found signiﬁ  cant improvement in time-limited individual and group 
therapies. It seems that most patients who are suitable for psycho-therapy will beneﬁ  t in either modality.
(b) Process research
(i) Preparation of patients for group therapy
In a review of 20 controlled or comparative studies, Piper and 
Perrault(102) found that preparation has a positive effect upon 
attendance but that it could not be shown to have a direct effect on outcome.
(ii) Therapist activity

Development of constructive group norms will depend on factors such as careful group composition and leadership style. Foulkes’ idea that the conductor has, at ﬁ  rst, a relatively high rate 
of activity which decreases as the group develops its own resources for psychological work has been supported by later research ﬁ ndings.
(103)
(iii) Group process variables
Research on therapeutic factors (e.g. self-disclosure and feedback) 
and leadership technique indicate that members in well-established groups are engaged in many different types of psychological work. They are less group-centred and more likely to be confronting the personal distress and maladaptive interpersonal styles that brought them to treatment in the ﬁ  rst place.
(104)
(iv) Therapeutic factors

(104)
In a study of long-term in-patient groups, Tschuschke and Dies(105)
investigated ﬁ  ve therapeutic factors: cohesiveness, self-disclosure, 
feedback, interpersonal learning-output, and family re-enactment. All ﬁ ve therapeutic factors were associated with clinical improve-
ment with group cohesiveness, an important ingredient. They suggested that affective integration  into the group, that is the high 
and positive emotional relatedness to co-members, promotes the capacity to disclose and leads to more frequent and intense feed-back from fellow patients. It appeared that feedback given earlier in the group had a stronger relationship to treatment outcome. This may suggest that interpersonal feedback  needs time to be 
assimilated and worked through before it can be utilized effectively. There are signiﬁ  cant differences between successful and unsuccess-
ful patients in terms of level of group cohesion and amount of

ful patients in terms of level of group cohesion and amount of 
self-disclosure. Patients who disclose little and do not feel drawn to 
the group receive relatively little meaningful interpersonal feedback and become neglected. They concluded that cohesiveness, self-
disclosure , and feedback  and together promote interpersonal 
learning  within the group.
These ﬁ  ndings were conﬁ  rmed by the author’s later studies, 
the most recent of which was published in 2007
(106) and by recent 
independent studies using different parameters; see, for example, references 
(107–109).
Conclusion: planning a service
For group psychotherapy to be effective the group has to be the primary focus of therapy; patients need to be well selected; and

1367
therapists need to be adequately trained. Therapeutic competence 
is not a function of mastering the literature so much as it is the outcome of experience in the group situation itself. Courses intro-ducing different group methods are now widely available through-out the UK, Continental Europe, and the USA. Group training is also provided in many general training programmes and, along with clinical supervision, is offered in many health and other service agencies.
Long-term outpatient  group therapy of 100 sessions or more is 
effective and economic in producing lasting beneﬁ  ts for patients 
with a wide range of medical and psychiatric symptoms, interper-sonal problems, traumatic life experiences, character and personal-ity disorders. In-patient  group therapy is an effective resource 
in the context of acute units working with crisis, and in secure units working with long-term problems. Short-term  group therapy for

in the context of acute units working with crisis, and in secure units working with long-term problems. Short-term  group therapy for 
selected conditions requires careful composition of the group and an active, ﬂ  exible therapeutic approach.
We have not tried to cover the range of group services and 
approaches for children. Chapters by Schamess
(110) and by 
Kymissis(111) cover group work with children and adolescents, respec-
tively. Further reading is available in Evan’s text(112) and Melzack.(113)
There are economic arguments for group therapy. In one study, 
the quality of improvement between individual and group therapy of psychiatric patients was not signiﬁ  cantly different but the cost

the quality of improvement between individual and group therapy of psychiatric patients was not signiﬁ  cantly different but the cost 
of the service was different. Cost savings were calculated as the reduction in medical consultations and hospital attendance, and lost workdays. For those treated with psychotherapy of any kind, the cost of treatment was 25 per cent per patient less than it was for those who did not receive psychotherapy. The cost of group psy-chotherapy per patient was about a third less than for individual psychotherapy.
(114)
A. Bateman, D. Brown and J. Pedder’s (2000) Introduction To Psychotherapy 
(Routledge) sets group therapy in the context of other psychotherapies. D. Stock Whittaker’s (1995) introduction, Using Groups To Help 
People (Routledge) and M. Aveline and W. Dryden’s (1988) Group 
Psychotherapy In Britain Today (Open University Press) give a general

Psychotherapy In Britain Today (Open University Press) give a general 
overview of UK practice in the past.  There are three good texts that 
introduce the group-analytic approach.  The most recent by H, Behr and L. Hearst (2005) is Group Analysis: A Meeting of Minds (John 
Wiley). W. Barnes, S. Ernst and K. Hyde have written a recent overview, (1999) An introduction to groupwork: a group-analytic perspective 
(Palgrave Macmillan). And an earlier text by D. Kennard (1993) The Workbook of Group Analysis (Routledge) provides a clinically 
grounded study of practitioners at work.  The range of other books in 
the International Library of Group Analysis and the journals, Group 
Analysis, Group, and The International Journal of Group Psychotherapy give access to the many specialist applications discussed here.
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52. Cox, M. and Theilgaard, A. (1987). Mutative metaphors in 
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53. Bennis, W.G. and Shepard, H.A. (1956). A theory of group 
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55. Foulkes, S.H. (1964). Therapeutic group analysis . George Allen and 
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56. Tschuschke, V . and Dies, R.R. (1994). Intensive analysis of therapeutic

56. Tschuschke, V . and Dies, R.R. (1994). Intensive analysis of therapeutic 
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57. Marziali, C. et al. (1997). The contributions of group cohesion and 
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60. Pines, M. (1990). Group analysis and the corrective emotional 
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61. Garland, C. (1982). Group analysis: taking the non-problem seriously. 
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62. Pines, M. (1995). The universality of shame: a psychoanalytic approach. 
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63. Nitsun, M. (1996). The anti-group: destructive forces in the group and 
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64. Salvendy, J.T. (1993). Selection and preparation of patients and 
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66. Roback, H.B. and Smith, M (1987). Patient attrition in dynamically 
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67. Melnick, J. and Woods, M. (1976). Analysis of group composition: 
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69. Zelakowski, P . (1998). The sub-optimal group. Group Analysis ,
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71. Leszcz, M. and Goodwin, P . (1998). The rationale and foundation 
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75. Kapur, R. (1993). The effects of group interpretations with the severely 
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6.3.7 Psychotherapy with couples
Introduction and background
There is an ongoing crisis in the institution of marriage, at least in

There is an ongoing crisis in the institution of marriage, at least in 
Western cultures. There has for some time been a tendency to idealize marriage, and at the same time social forces are operating which tend to undermine it.
(1) These inﬂ  uences have probably 
made a contribution to the increasing divorce rate, as well as the tendency for fewer couples to marry, and have probably also led to an increase in the number of couples seeking help with their relationships.
In the United Kingdom, for example, the number of marriages 
taking place each year has fallen for the ﬁ  rst time in living memory, 
and the number of divorces is still steadily increasing, reaching 40 per cent of marriages in 1996.
(2) There are also a large number

(2) There are also a large number 
of ‘common-law’ marriages, often with children, as well as more transient cohabiting or non-cohabiting sexual relationships, both heterosexual and homosexual. The stability of these relation-ships is, of course, not recorded in the marriage or divorce statis-tics, and the rate of breakup can only be guessed at; however, it is very probable from clinical experience that in these non-marital relationships there is a higher than 40 per cent incidence of breakup. In the wake of these changes, there are a large number of 6.3.7 psychotherapy with couples

SECTION 6  treatment methods in psychiatry 1370
single-parent families and ‘reconstituted’ or blended families, as 
reviewed by Robinson,(3) and there is a decreasing proportion of 
children who are being brought up in the traditional nuclear family with two biological parents.
In addition to these new factors affecting marriage in the 
early 21
st century we should also be aware of the fact that many 
countries, especially those in the developed world, have a multicul-tural society, and that immigrant cultures have different attitudes to marriage and family life. For example, families from the Indian subcontinent often prefer to arrange marriages for their children, and in some cases insist that the couple live in the hus-band’s parents’ house. On the other hand, West African couples often leave their children in Africa to be looked after by family members for long periods of time, while the parents work or study in the West.

In the last few years, Gay marriage or Civil Partnership has been 
recognized in many western countries. Couples in Gay relation-ships have many of the same problems and satisfactions as hetero-sexual couples, and in addition, must live with fairly widespread 
negative attitudes and homophobia from neighbours, family 
and society generally. Their relationships have to be, if anything, stronger than heterosexual ones to survive these pressures, and may be more in need of therapy.
Couple therapy must be able to take account of these factors, 
and whilst much of what is contained in this chapter will relate to heterosexual married British couples living with their biological children, it should be understood that there are many other types of relationship which can be helped using a similar approach, with appropriate changes of emphasis. In a later section, there will be some additional discussion of the speciﬁ  c problems relating to

couples from other cultures, and ways of managing these.
Couple counselling and couple therapy
The concept of couple counselling dates from the 1920s when in the United States the American Association for Marital Counselling was formed; in the United Kingdom the Marriage Guidance Council (now called Relate) was founded in 1938. Counselling mainly took the form of giving advice on practical issues, but in more recent years, Relate counselling has been orientated more towards psychodynamic approaches, and favours a longer-term involvement with the couple. Couple counselling continues in both countries, and the great majority of couples seeking help with their relationships are seen by couple counsellors, rather than any other types of therapist.
The distinction between couple counselling and couple therapy

The distinction between couple counselling and couple therapy 
is not an easy one, because many of the interventions are similar. In a simplistic sense therapy attempts to make a more radical difference to the couple’s functioning than counselling, which has 
the general aim of improving adjustment to the situation as it is. 
However, many forms of both couple therapy and couple counsel-ling are based on a theoretical formulation which is derived from a related school of individual psychotherapy (for example, cognitive behavioural or psychodynamic). Thus, theoretical formulations in the resultant couple work are so different between therapies (e.g. psychodynamic as against behavioural) that a particular form of counselling may have more in common with a related form of couple therapy than that therapy itself has with another type of couple therapy.Psychoanalytic/psychodynamic couple 
therapy
Couple therapy using a psychodynamic model began in the United

therapy
Couple therapy using a psychodynamic model began in the United 
Kingdom in 1948, when Dicks and his colleagues founded the Institute of Marital Studies. The theories and techniques involved have been ably reviewed by Daniell
(4) and Clulow.(5) The central 
concept used is that the inner (unconscious) world of the two part-ners determines their interaction and their response to changing circumstances. It is as though each partner has an internal blue-print, both of themselves and each other, formed partly by observa-tion but also partly by the inﬂ  uence of earlier intimate attachment 
experiences with parents, siblings, or friends. These inﬂ  uences may

experiences with parents, siblings, or friends. These inﬂ  uences may 
actually determine the choice of partner, and the nature of each partner’s patterns of attachment (secure or insecure) will affect the ways in which they cope with the stresses of the new relationship. There may then be projections which lead one partner to attribute motives such as hostility or sadism to the other, whereas in fact this is a split-off and denied characteristic of the ﬁ  rst partner. Other 
consequences of this unconscious process may include the system 
of shared fantasies and defences which builds up as the relationship 
continues.
In therapy, four premises are used, which inform a relatively 
long-term and open-ended series of sessions. The ﬁ  rst is that a 
person’s emotional health is related to his or her capacity to manage both internal conﬂ  ict and external stress: it is important to be able

person’s emotional health is related to his or her capacity to manage both internal conﬂ  ict and external stress: it is important to be able 
to experience fear as well as trust, pain as well as pleasure, doubt as well as certainty, frustration as well as satisfaction. Secondly, signiﬁ  cant relationships can be used to resurrect, but also change, 
inﬂ exible patterns of behaviour established in the past. Thirdly, 
unconscious processes need to be taken into account when attempt-ing to understand problems in relationships. Fourthly, change takes time because it requires a reordering of perceptions of self and others, perhaps with the help of transference interpretations by the therapist involving both partners.
Therapy in this mode may be carried out by one therapist seeing

Therapy in this mode may be carried out by one therapist seeing 
both partners, but is more often done by two therapists either seeing the couple together or in parallel individual sessions, using one partner with one therapist, with joint supervision of the two therapists. An intriguing aspect of this therapeutic format is that sometimes the two cotherapists ﬁ  nd themselves interacting in 
unfamiliar ways, in sessions and between sessions, which are thought to represent the projection of fantasies and feelings by the couple on to the therapists; the therapists’ understanding of these projections in their joint supervision may play a role in advancing the therapy itself. If these insights are used to inform the therapists’ interaction with the couple, the individual partners may then be made aware of their own conﬂ  icts, fantasies, and projections, 
and thus be able to give up some of their repetitive patterns of 
behaviour and withdraw damaging projections.

The psychoanalytic approach has been an important source of 
theoretical ideas in couple therapy, especially the concepts of attachment and loss developed by Bowlby.
(6) It has also the distinc-
tion of being the ﬁ  rst theory to be adapted to this area of work. 
There are, however, some drawbacks to working in this way, as enumerated by Wile.
(7) He sees the emphasis on negative impulses 
and emotions (e.g. dependence, narcissism, sadism, manipulation, and exploitation) as painting a rather unﬂ  attering and negative 
picture of the couple in therapy, and perhaps therefore reducing

1371
their motivation to continue. A more serious problem with the 
approach is that the psychodynamic concepts, whether of defence mechanisms, projections, or shared fantasies, are treated as if they were as real as observed behaviour, whereas in fact they must remain assumptions based on hypothetical constructs, and are really only valuable in so far as the therapy based on them is effective.
(1)
The question of efﬁ  cacy is raised later in the chapter, but it 
must be stated here that the psychodynamic therapies for couple problems have only seldom been submitted to controlled trial, and then usually in a relatively short-term form. The therapy may be quite long term, and the improvements seen are usually not dra-matic, so that in the last analysis the approach has to remain of uncertain value.
Behavioural couple therapy
The behavioural approach, in contrast, makes no assumptions about internal conﬂ  icts or underlying mechanisms in the individu-

als. The approach was initiated in 1969 by Stuart
(8) and Liberman(9)
as behavioural marital therapy. They worked from the principles of operant conditioning and made the assumption that couples who were having difﬁ  culties were either giving each other very low 
levels of positive reinforcement or were using punishment or nega-tive reinforcement to coerce each other into behaving differently. The remedy that they proposed for this situation was to help the partners to learn how to persuade each other to conform to the desired pattern of behaviour by the use of prompting and positive reinforcement. Thus, complaints would be transformed into requests and requests into tasks agreed by both partners.
Behavioural marital therapy relies on the therapist’s observation

Behavioural marital therapy relies on the therapist’s observation 
of the couple’s behaviour in the session and on the problems they report from the previous week or equivalent timespan. There are 
two types of therapeutic activity in behavioural marital therapy. The ﬁ  rst is reciprocity negotiation, in which the partners request 
changes in behaviour on each side and negotiate how this can be achieved through mutually agreed tasks. The second is communi-cation training, in which the partners are encouraged to speak directly and unambiguously to each other about feelings, plans, or perceptions, and to feed back what they have heard and under-stood. In both these approaches, the deeper meanings behind a particular piece of behaviour are ignored, the emphasis being on change in the interaction both in the here and now and in the immediate future. The approach has been the subject of many controlled trials (see below), and is of proven efﬁ  cacy.
Cognitive behavioural and

Cognitive behavioural and 
rational–emotive couple therapy
Aaron Beck,(10) in his cognitive behavioural approach to couple 
therapy, identiﬁ  es in the communication of disturbed couples many 
of the problems found in the thinking of depressed patients, and attempts to correct these. Thus, he tackles misunderstandings, gen-eralizations, untested assumptions, and automatic negative thoughts by challenging assumptions, reducing unrealistic expectations, relaxing absolute rules, improving the clarity of the communication and focusing on the positive rather than the negative.
Similarly, Albert Ellis (reviewed by Dryden
(11)) uses a rational-
emotive approach to couple problems. Here, the main focus is on the use of words; terms such as ‘intolerable’ are replaced by (for 
example) ‘difﬁ  cult to accept’ , and the couple are encouraged to

example) ‘difﬁ  cult to accept’ , and the couple are encouraged to 
express desires rather than demands. There is an analysis of the repetitive cycles of cognitive and behavioural disturbance, in which each partner may attribute the other’s behaviour to a negative motive and assume that nothing can be done about it. The general thrust of this therapy is similar to that of Beck, but with a more lively and less formalized approach in the session.
Systems therapy for couple problems
The systems approach to couple therapy derives partly from concepts developed by Minuchin
(12) and Haley,(13) and partly from the work 
of Selvini Palazzoli et al.(14) All these pioneers worked predominantly

of Selvini Palazzoli et al.(14) All these pioneers worked predominantly 
with families rather than couples, but many of their ideas and tech-niques are relevant to the treatment of couples. Although the systems approach to therapy has broadened and deepened since the 1980s, many of the early concepts are still very useful.
A central concept in thinking about couple relationships is 
‘enmeshment’ , by which is meant an excessive involvement in what is essentially the private business of another person. It is quite common to ﬁ  nd an enmeshed relationship between parents and 
their teenage children, in which both sides ﬁ  nd it very hard to ‘let 
go’ . It can also be found in couple relationships where one partner wants to be closer than the other, and a conﬂ  ict arises as to what is 
the best distance to maintain. Systems therapy aims to help them to ﬁ nd a compromise ‘distance’ which suits them both, and thereby

the best distance to maintain. Systems therapy aims to help them to ﬁ nd a compromise ‘distance’ which suits them both, and thereby 
to reinforce the necessary ‘boundaries’ which people need in main-
taining their individuality within a relationship.
The concept of circular causality is also central to systems work. 
This enables the couple to get away from the idea that one person is necessarily to blame for a particular situation by considering the continuous cycle of cause and effect in which A ’s actions may be caused by B’s actions and also B’s may equally be caused by A ’s. Thus, systems therapists, when approaching a couple problem, do not focus on one partner’s behaviour, but rather on the pattern of interaction obtaining in the relationship. They will then try to effect a change in which both partners contribute actively to the solution of the problem.
Systems therapists have many techniques at their disposal, includ-

ing those which increase the couple’s understanding of the system they are participating in. These include family genograms (a form of family tree construction which leads to discussion of transgenera-tional inﬂ  uences or ‘systems over time’), family ‘sculpting’ (in which 
the members position themselves and each other wordlessly to represent their current relationships), and the discussion of ‘family myths’ and stories. More active techniques, designed to play a part in changing the family interaction, include creating conﬂ  ict in the ses-
sion, giving homework tasks, and the use of ‘paradoxical injunctions’ 
in which the therapist tells the family to continue with the current interaction because, even though it is problematic, it seems to be 
protecting them from worse consequences. These more active techniques will be dealt with in more detail in the main part of this chapter on behavioural–systems therapy.

Mixed or eclectic approaches
Most couple therapists use a mixture of techniques, and it seems that this is probably an inevitable consequence of the difﬁ  culties 6.3.7 psychotherapy with couples

SECTION 6  treatment methods in psychiatry 1372
involved in applying one therapeutic method rigorously in a clinical 
setting. A number of speciﬁ  c combinations have been advocated, 
and will be brieﬂ  y mentioned here.
The first is the psychodynamic-behavioural approach of 
Segraves.(15) In this, the basic underlying cause of marital distur-
bance is assumed to be the partners’ conﬂ  icting internal and uncon-
scious projections, and their interactions. The therapy, however, 
is not only directed at helping them to understand these (as in 
psychodynamic therapy) but also to increase their negotiating and 
communicating skills (as in behavioural marital therapy).
The second is a more comprehensive mixture of theory and 
technique, known as the intersystem model, and advocated by 
Weeks.(16) This tries to take account of the individual, interactional, 
and intergenerational aspects of couple relationships, and com-
bines them in what is probably closest to a systems model, but with

bines them in what is probably closest to a systems model, but with 
more emphasis on the psyche of the individual. Interventions 
are on both a conjoint and individual basis, and the techniques 
of decentring (see below) and paradoxical injunctions are often 
used.
The third eclectic approach is that of Spinks and Birchler.(17)
This is called behavioural–systems marital therapy, and makes use 
of behavioural marital therapy as the main form of intervention, 
moving into the systems mode when ‘resistance’ emerges. There 
are many similarities between this form of treatment and the one 
described in the main part of this chapter, but our ‘behavioural–
systems approach’ is more integrated as between the two compo-
nents of the method.
The fourth eclectic approach which should be mentioned is that 
of Berg-Cross.(18) She uses rational-emotive, sociocognitive, 
systemic, psychodynamic, humanistic, and theological concepts

systemic, psychodynamic, humanistic, and theological concepts 
to understand and modify couple relationships. Like that of 
Weeks, her approach gives the therapist a very wide canvas to work 
on, but may lose some of the focus by being very general and 
all-embracing.
The behavioural–systems approach to 
couple therapy
Behavioural–systems couple therapy is the approach that will be 
described in detail in the present chapter, and although it is only 
one of several approaches to couple problems, it has the advantage 
of spanning two of them, and issues such as indications for therapy 
and assessment are shared with both the pure behavioural and 
systemic approaches. It is the method developed at the Maudsley 
Hospital Couple Therapy Clinic in the 1980s. It has been expounded 
at greater length by Crowe and Ridley,(1) and like some of the other

at greater length by Crowe and Ridley,(1) and like some of the other 
eclectic models mentioned above it combines two different 
approaches, behavioural marital therapy and systems family therapy. 
The behavioural dimension, similarly to that described by 
Stuart (8) and Jacobson and Margolin,(19) consists of the relatively 
straightforward methods of reciprocity negotiation and communi-
cation training. The systems dimension is more complicated, and 
involves systems thinking, structural moves during the session, 
tasks and timetables for the couple between sessions, and the use of 
paradox. The method was developed in a predominantly psychiat-
ric setting, and has been found to be particularly suitable for those 
couples where one or both partners has psychiatric problems in 
addition to their relationship difﬁ  culties. It is also useful as an adjunct to psychosexual therapy where a sexual dysfunction or a

addition to their relationship difﬁ  culties. It is also useful as an adjunct to psychosexual therapy where a sexual dysfunction or a 
sexual motivation problem seems to be connected with relation-
ship issues.
The method should be thought of as a series of menus from 
which the practitioner can choose techniques rather than as a set 
course of therapy beginning at one point and ending at another. 
Thus, the various components of behavioural–systems couple 
therapy can be incorporated at any time in the therapy session, 
although in practice, negotiation, communication training, and 
structural moves are usually employed in the earlier part of the 
session, while tasks, timetables, and paradox are usually reserved 
for the ‘message’ at the end, and are linked to homework assign-
ments to be carried out between sessions.
The different techniques of behavioural–systems couple therapy

The different techniques of behavioural–systems couple therapy 
can be thought of as belonging to a kind of hierarchy. The so-called 
‘hierarchy of alternative levels of intervention (ALI)’(1) links each 
type of intervention with a particular set of clinical problems and 
makes recommendations as to the type of intervention that is 
appropriate. The ALI hierarchy is shown in diagrammatic form in 
Fig. 6.3.7.1. As may be seen, where the couple appear to have greater 
rigidity in their behaviour, where they show more symptoms, and 
where they show more reluctance to accept the relationship as the 
focus of work, the therapist needs to move to the systems end of the 
hierarchy, and use more ingenuity in the development of interven-
tions. If, however, the couple accept the interactional focus and 
show willingness to recognize the part that the relationship is play-

ing in maintaining the problems, the therapist may be quite com-
fortable and effective working behaviourally. By and large, the 
preference is to work behaviourally, since this implies collaborating 
with the couple and accepting their stated goals, whereas the systems 
approach puts the therapist into a more managing role, deciding 
what is best for the couple and suggesting tasks that may not be what 
they would expect. It should be emphasized that the therapist may 
at any stage move up or down the hierarchy, according to the cou-
ple’s response: an increase in ﬂ  exibility shown by the couple could 
be the trigger for the therapist to begin working in a more behav-
ioural way, whereas an increase in rigidity or a failure to respond to 
behavioural work could be met by a more systemic approach.
Couple characteristics:

Therapist interventions:More symptoms
Individual focus
Rigidity of the system
7. Cease treatment or use other therapies
6. Adjust to the symptoms
5. Paradox
4. Timetables and tasks
3. Induce arguments
2. Communication training
1. Reciprocity negotiation
More need for therapist
ingenuity
Less reliance on couple’s
stated goals
Fig. 6.3.7.1 The alternative levels of intervention hierarchy.

1373
If there is a relationship problem identiﬁ  ed by either the couple or 
their advisers, even if there are also individual psychiatric or behav-ioural problems, and if the couple are willing to attend together, then in most cases they are suitable for behavioural–systems couple therapy. The breadth of the therapeutic approach, the fact that the behavioural techniques are of proven efﬁ  cacy (see below), and the 
fact that the systemic interventions are suitable for those with more psychiatric symptoms or similar problem behaviours, all give the 
therapy a wide range of positive indications.
(a) The nature of the problem
Clearly those with relationship problems such as arguments and

Clearly those with relationship problems such as arguments and 
tensions are highly suitable for couple therapy. Another related indication is those relationships in which one partner (who might be attending a counsellor or psychiatrist alone) spends much time complaining about the absent partner’s behaviour. A third indica-tion is where the health of one partner suffers following the other partner’s individual therapy.
Many problems with sexual function would be suitable for 
couple therapy, including those couples where there is a disparity in sexual desire, or those where one partner has a speciﬁ  c phobia 
for sex. In some such cases there is also a need for individual therapy, especially where one partner is the survivor of earlier childhood sexual abuse.
Many people with depression or anxiety, especially those where 
there is also poor self-esteem, may be suitable for couple therapy.

there is also poor self-esteem, may be suitable for couple therapy. 
There are often aspects of the illness that are exacerbated by problems in the relationship. Indeed, in a study by Leff et al.  in 
2000
(20) it was shown that couple therapy was an effective and 
acceptable form of treatment for couples in whom one partner was depressed.
Where jealousy is present the problem usually affects the non-
jealous partner to a greater or lesser extent, and here it would almost always be useful to have at least a few conjoint sessions with the couple, as suggested by De Silva.
(21)
Some problems are perhaps less amenable to couple work, and

(21)
Some problems are perhaps less amenable to couple work, and 
among these are, for example, phobias which seem unconnected with home life in any way, and post-traumatic stress reactions where the event happened away from the partner. Some alcoholic and drug-addicted patients have so much of their existence involved with the addiction that they are not available emotionally to do couple work, and the work would at that stage be wasted on them. Similarly, those with an acute psychosis would, at the time they are acutely ill, be unavailable to this kind of therapy, and should not be offered it. However, in both cases, when the acute crisis is over and the addiction or psychosis is under control, it would be very appropriate to offer them some kind of couple therapy, even if this had limited aims and expectations. Some of the most useful psychological interventions in schizophrenia, after the acute 
illness has resolved, involve the nearest relative, as shown by 
McFarlane.
(22)

(22)
(b) Degree of connection with the relationship
Some problems in individuals have been in existence long before they entered the present relationship. If this is the case, the thera-pist should consider whether it is best to embark on couple therapy or whether individual therapy would be better. However, even when there seems no causal connection with the relationship, the effect of the problem on the partner may be such as to warrant at 
least one or two couple sessions.
(23)
(c) Availability and willingness for joint therapy

(23)
If the partner of a patient is unavailable or unwilling to attend for therapy, it may be appropriate to let the situation be, and not offer treatment. In some immigrant couples, for example those from the Indian subcontinent, there are cultural reasons given for a wife not attending therapy, and we usually have to respect these. However, in both situations it is sometimes right to put some pressure on the absent partner to attend, because the reasons for non-attendance may be relevant to the couple problems we are trying to treat.
(d) Is the relationship continuing?

If the person who is asking for therapy is going through a divorce or equivalent breakup of a relationship, it may not be appropriate or possible to treat both partners. However, in some cases there is good work to be done in arranging a more satisfactory breakup, in terms of domicile and care of any children. This ‘mediation’ work is increasingly being done, and many of the processes are similar to those of couple therapy.
Assessment and selection
This is not an easy process, because there is a dearth of research on the types of couple problem presenting for treatment and on the outcome of treatment itself. However, on the basis of the referral letter (usually from a GP or psychiatrist) the therapist will usually arrange a preliminary session with the couple. The only reason not to see the couple in the ﬁ  rst instance is that they are not willing to 
attend as a couple, or the problem is seen clearly as an individual one (see above).

Another, more subtle, form of selection occurs during the ﬁ  rst 
therapy session, when the couple are in contact with the process of therapy. In this session, the therapist considers the ability of the partners to empathize with each other, their pattern of communi-cation, their stage in the ‘family life cycle’ (see below) with its associated stresses, and their ﬂ  exibility in response to simple thera-
peutic interventions. He or she will attempt to use reciprocity 
negotiation or other straightforward techniques of therapy, partly 
as a treatment trial, and partly to see whether the couple is ready for this kind of intervention. If not, the therapist can move to a more systemic approach, or decide after a few visits that there is no future at this point in further therapy of this kind, and that something else (e.g. individual therapy) is needed (Fig. 6.3.7.1).

The process of therapy: beginning and continuing
Behavioural–systems couple therapy is essentially a short-term therapy involving perhaps 5 to 10 sessions of 60 minutes each, over a period of 3 to 6 months. Although the therapy was developed in a room with a one-way screen and live supervision, it is quite possible to use behavioural–systems couple therapy in any conven-tional consulting room without a team or live supervision. If the one-way screen is used, the therapist and the team (which may include students as well as experienced colleagues) begin by read-ing the referral letter and the biographical questionnaires which the couple will have completed, and discuss the case with a view to formulating the problem from an interactional point of view. This may involve, for example, thinking about the couple’s stage in the ‘family life cycle’ (e.g. birth of the ﬁ  rst child or the ‘empty nest’), 6.3.7 psychotherapy with couples

SECTION 6  treatment methods in psychiatry 1374
any recent event such as a bereavement or a new relationship, or 
the diagnosis of a serious illness. Hypotheses about the possible causation of the recent problems are not necessarily thought of as ‘true’ explanations, but have the function of informing the thera-pist’s thinking and suggesting what level of the ALI hierarchy to choose at the initial meeting and what strategy to employ in the session.
There are several important issues to address in the ﬁ  rst session, 
which functions both as a kind of assessment and as the beginning of the therapeutic work. It is necessary:
◆ to remain in control;
◆ to develop rapport with both partners, without favouring either;
◆ to maintain the momentum of the session and the interactional 
focus;
◆ to maximize the opportunities for the couple to experience 
a change in the nature of their interaction.
A particularly useful move at some stage in the ﬁ  rst session, and

focus;
A particularly useful move at some stage in the ﬁ  rst session, and 
one which we almost always use, is to ask the partners to talk directly to each other rather than the therapist; this is the so-called ‘decentring’ technique originated by Minuchin.
(12) Keeping this 
conﬁ  guration for as much as possible of the session enables the 
therapist to observe the couple’s typical pattern of interaction, to intervene as a ‘theatrical producer’ rather than a diplomatic negotiator, to avoid as far as possible taking sides, and to encourage the kind of negotiation which hopefully the couple will be able to carry on at home without the presence of a third party. It is not necessary to remain decentred for the whole session, but if it does not happen at all in the ﬁ  rst session, an opportunity for effective 
work will have been lost.

It may be difﬁ  cult to remain decentred in the face of pressures 
from one or both partners to talk to the therapist directly. One way to participate while still remaining decentred is to request the part-ners to ask each other questions to which the therapist would like to 
know the answer. For example, one might say: ‘Could you ask your 
partner what she thinks about your coolness on this matter?’ or ‘Perhaps your partner disagrees with you; could you check with him?’ . In this way the couple can continue to talk to each other in the decentred position without undue ‘triangling in’ of the therapist.
One situation which causes particular problems for the

One situation which causes particular problems for the 
behavioural–systems therapist is where one partner persists with monologues, either about his or her own symptoms and problems or about the partner’s unreasonable behaviour. This is a perfectly acceptable way to present a problem in one-to-one therapy, but in couple therapy it slows down the interaction and prevents the therapist focusing on the relationship. One way to overcome this is by decentring, but in some couples this is too difﬁ  cult, and another 
possibility is to ask the non-verbal partner to comment on the spokesperson’s problems. This can provoke a minor crisis in the couple, and lead to the spokesperson realizing that the problems are not all one-sided. It is a technique related to circular questioning, and is used fairly extensively in family therapy see Chapter 6.3.8
Another obstacle to progress is the situation in which the 
partners have intractable arguments, perhaps about other family

partners have intractable arguments, perhaps about other family 
members. If such battles continue to dominate the sessions the 
therapist may have to devise a method for putting them ‘on ice for the time being’ and concentrating instead on negotiating everyday problems to do with the house or the children.Momentum may also be slowed by the therapist’s own style of 
working. Students of the behavioural systems approach may need to ‘unlearn’ some of their otherwise good therapeutic habits such as being a good and empathetic listener. They may be able to achieve this by decentring or by asking circular questions in order to refocus on the interaction and increase momentum.
On the other hand, it is still important for the therapist to be able 
to feel and show empathy to the two individuals in therapy. The difﬁ culty may be that to show empathy to one partner may be

to feel and show empathy to the two individuals in therapy. The difﬁ culty may be that to show empathy to one partner may be 
interpreted by the other as side-taking. A possible remedy lies in 
a particular skill, which, however, is not easy to acquire, of saying something to show that one has understood one partner without antagonizing the other. One way to develop this skill is for the therapist not to become emotionally involved in the issues, but to concentrate on the process of interaction, thinking all the time in terms of balance and communication rather than worrying about the rights and wrongs of what is being discussed. This must be done while still showing respect to both the partners, taking their problems seriously, and at the same time conveying hope that they can be solved.
It is also very helpful for the partners themselves to be in touch

It is also very helpful for the partners themselves to be in touch 
with each other emotionally and take each other seriously. Some individuals are very good at communicating, but only at an intellectual level, and cannot express empathy with each other. Their interaction is like that of fellow committee members, and they tend to suppress any expression of feelings such as sadness or anger which are ‘not on the agenda’ . In other couples, there is an imbalance, with one partner expressing feelings openly and the other being exclusively logical and self-controlled. In both situa-tions it is necessary to help them to communicate both intellectu-ally and emotionally, encouraging the self-controlled individual to be more open and the person who is emotionally open to try to be more restrained at times.
Ending the session

Every session must have an ending, and the purpose in the behavioural–systems approach is to send the couple away with something to work at in the weeks before the next session. About two-thirds of the way through a supervized session the therapist will usually go behind the one-way screen, turning off the camera and closing the shutters (although when working alone this luxury is not available and the therapist must work independently to end the session on a positive note). The team and the therapist then spend about 15 minutes in discussion, planning the ‘message’ to be given to the couple at the end. Part of this discussion will centre round the team’s thinking about the signiﬁ  cance of the 
problems from a systems point of view, but part will also be con-cerned with how the therapist can help the couple to change their interaction.
The introduction to the message will give the date of the

The introduction to the message will give the date of the 
next appointment, and usually also contains some positive and sympathetic comments for both partners. It is important as far as possible to keep them both ‘on side’ at this stage, so that it would be unwise to say something which could be seen by either partner as favouring the other one. A good example of an introductory comment would be: ‘The team and I are aware of the great difﬁ  cul-
ties you are experiencing, but we think you have what is basically a good relationship, and you are both working hard to improve things’ .

1375
The message itself will vary according to the level of the hierar-
chy at which the therapy is being pitched. If it is mainly a session of reciprocity negotiation the main theme may be simply to reiter-ate the negotiated plans for both partners which have emerged from the earlier discussion. If, however, the therapist is working more systemically, the message may contain a task, a timetable, or a paradoxical injunction which is designed to alter both the behaviour of the couple and the way they conceptualize their relationship. In some cases, it is appropriate to use a ‘split-team’ message , in which one part of the team is said to favour a more behavioural task while the other part believes that that will be impossible to achieve and therefore prefers to ‘prescribe the symptom’ .
The ﬁ  nal part of the message is again likely to reiterate the posi-

tive sentiments of the introduction. There are good therapeutic reasons for this, in that people tend to remember the positive things that they hear about themselves, and may then link these to the more specific tasks or injunctions that are given with them. In many cases we also send a written copy of the message to the couple, so that they can think it over between sessions and not forget what has been discussed.
Where therapists are working alone, they will be unable to have 
the 15 minute break in the session, but it is always useful to spend a little time thinking about the message to be given at the end of the session, and to think what other team members might have said or suggested for a ﬁ  nal message.
Speciﬁ  c techniques in behavioural–systems 
(a) Reciprocity negotiation
Within the alternative levels of intervention hierarchy, reciprocity

Within the alternative levels of intervention hierarchy, reciprocity 
negotiation is at the lowest level, relating closely to the goals that the couple themselves has set, and depending on a fairly co-operative attitude on both sides. The partners state their complaints in every-day terms, and the task of the therapist is then to help them to achieve a compromise by each doing what the other partner wants in a reciprocal way.
Reciprocity negotiation is partly based on operant conditioning 
and partly on the social exchange theory of Thibault and Kelley.
(24)
The assumption is that satisfaction in marriage and other intimate 
relationships is based on a relatively equal and high level of input 
by each partner of positive (i.e. rewarding) behaviour and a rela-

tively low input of negative or unacceptable behaviour. Problematic marriages have a low level of these mutually rewarding behaviours on both sides, or may have a gross imbalance in the input from the two different partners. Instead of exchanging positive behaviour, the partners may use coercive methods to try and force the other to stop doing those things of which they disapprove.
The remedy proposed by behavioural marital therapy is that each 
partner should state their complaints , but that these complaints 
should then be translated into wishes  for an alternative way of 
behaving which is more acceptable, and, as a second stage, into tasks . It is very useful to concentrate on practical, domestic issues

behaving which is more acceptable, and, as a second stage, into tasks . It is very useful to concentrate on practical, domestic issues 
for these tasks, as these are easily grasped, frequently repeated, and more likely to be remembered than more abstract tasks. In principle the tasks for each partner should be linked and recip-rocal, but if this is not possible a ‘bank account’ approach can be used in which each partner builds up a fund of good behaviour and they work out at the end of a period of time whether it has 
been mutually acceptable. In moving from complaints to tasks one also moves from past to future, and this is one of the most charac-teristic features of reciprocity negotiation. The therapist is thus more interested in what will happen next week than in what hap-pened last week or last year.
The way that reciprocity negotiation is used in behavioural–

systems couple therapy is a little different from its use in behav-ioural marital therapy. We will usually have the couple in a decentred position while negotiating, and feel that this helps the process both to be effective, and to translate more successfully to their home setting. We also use it quite brieﬂ  y at different stages of 
therapy, rather than as the mainstay of therapy throughout.
The tasks developed for each partner in reciprocity negotiation 
should be:
1 speciﬁ  c,
2 positive,
3 repeatable,
4 practicable, and
5 acceptable to both partners.
They should also be concerned with everyday activities, rather 
than once-only events such as arranging an overseas holiday. Sometimes sexual problems can be brought in to the negotiation.
Reciprocity negotiation is a well-tried and effective method of

Reciprocity negotiation is a well-tried and effective method of 
couple therapy in those who accept that they have marital prob-lems. It is also an advantage that the therapist here works in a way which is straightforward and takes an adult-to-adult approach. But it is also, in our setting, a way of assessing whether the couple are ready for this sort of intervention; if not, they can be offered a more systemic input until they are more ready to negotiate.
(b) Communication training

The second strategy in the alternative levels of intervention hierarchy is training in communication. This too is part of the behavioural marital therapy spectrum, but not so exclusively, because work on communication is part of most types of couple therapy. The char-acteristic feature of the form of communication training used in our setting, however, is that it aims for efﬁ  cient and clear commu-
nication, with positive and constructive requests rather than com-plaints. Other forms of communication training
(25) emphasize 
other skills such as empathy, reﬂ  ective listening, and supportive 
comments. In the present form of communication training these are also issues to be considered, but the main emphasis is on issues such as reducing misunderstandings, ensuring that both partners have an equal say, and helping them both to speak from the ‘I’ position.
Problems encountered in couple therapy amenable to communi-
cation training include:
◆ lack of empathy

◆ inability to express emotion
◆ failing to listen
◆ monologues with no break for feedback
◆ one partner the spokesperson and the other silent
◆ mind-reading (i.e. A knowing better than B what is in B’s mind)6.3.7 psychotherapy with couples

SECTION 6  treatment methods in psychiatry 1376
◆ sting in the tail (a positive comment followed by a criticism)
◆ wandering off the topic
◆ continual criticism.
In carrying out communication training, the therapist ﬁ  rst 
decentres him- or herself, and asks the couple to converse about a relevant topic. When a problem of communication arises the therapist acts as a ‘director’ and asks them to discuss the topic in another way. If the problem observed is one of lack of empathy, this may include asking one partner to attend to the emotional state of the other, and perhaps to feed back his or her understanding. If it is of inability to express emotion, the therapist may try to intensify the interaction, pointing out the way in which they are holding back their emotions, and encouraging more expressiveness.
The next three problems are connected: failing to listen, talking

The next three problems are connected: failing to listen, talking 
in monologues, and the ‘spokesperson’ problem. Remedies can be decentring, encouraging each partner to speak for him- or herself, stopping the talkative partner (perhaps by asking them to listen to what the other partner has to say), and cutting any monologues short by asking for feedback from the other partner. In dealing with mind-reading one may have to be quite diplomatic, because the process is rather similar to psychotherapeutic interpretation, and some partners may feel that this is a legitimate way of giving insight; however, it should be tactfully blocked, usually by asking the partner whose mind is being ‘read’ to say whether that is what he or she really thinks.
The ‘sting in the tail’ is dealt with usually by simply pointing it 
out, but in some cases it can be neutralized by asking the speaker 
to restate the idea the opposite way round with the ‘sting’ ﬁ  rst.

to restate the idea the opposite way round with the ‘sting’ ﬁ  rst. 
An example of this is given by a man who said ‘I realize you were hurt by what I did, but I had no intention to harm you (i.e. you are being oversensitive)’ . He was asked to rephrase it as ‘I had no inten-tion to harm you, but I realize that you must have been hurt’ , and his wife found this much more acceptable, because she could respond to the more positive part of the comment.
The problems of wandering off the topic and continuous 
criticism are often rather intractable. One way, however, of keeping them to task is to bring them back frequently to the problem ﬁ  rst 
presented, and ask whether they can concentrate on solving it. In the case of mutual criticism, one way of coping is to slow down the interaction so that each partner speaks only after the therapist has intervened to reframe what has just been said.

As with reciprocity negotiation, communication training is used 
not as a self-contained therapy in itself, but rather as part of a menu of techniques to be chosen according to the problem presented or observed at the time.
(c) Structural moves in session
The main interventions under this heading are raising arguments (or heated discussions) in the session, reversed role play, and ‘sculpting’ .
There are many couples in which there is a reluctance to enter 
any sort of conﬂ  ict. They avoid differences of opinion, and pretend 
that there is agreement on almost every issue. The more dominant 
partner, usually more at ease verbally, effortlessly takes the spokes-person role. The other partner is either silent much of the time or 
spends much effort placating the other in order to reduce conﬂ  ict.
One strategy with such couples is to ask them to argue (or, to put

One strategy with such couples is to ask them to argue (or, to put 
it more acceptably, to have a heated discussion ) about a fairly trivial topic. An example of this might be whether the toilet seat 
should be left up or down after it has been used. It must be a genu-ine difference of opinion, and not simply one manufactured for the purpose, but it is important that it should be of a trivial nature, as otherwise the couple may feel inhibited about discussing it.
They are then asked to discuss the issue with the therapist observ-

ing, and the therapist particularly encourages the more submissive partner to participate with enthusiasm. It may be necessary to ask him or her to speak louder, or to ask the other partner to listen more carefully to what the quiet partner has said, but the therapist should not take sides as such. What is being dealt with is not the issue itself, but the process of arguing. The outcome does not matter, except that the submissive partner should not be allowed to ‘get away with’ their usual tactic of giving in for the sake of peace. The couple may ‘agree to differ’ or the submissive partner may have a better than usual hearing, and even win the argument.
This intervention is particularly useful for those couples where 
there is a degree of depression in the quieter partner, or where the quieter partner is very reluctant to be involved sexually, and is blaming him- or herself.

Another intervention in session which can have an impact on the 
interaction is the ‘ reversed role play ’ . Here the couple is asked to 
discuss a particular issue, but they are asked to act as if they were 
the other partner, even perhaps changing chairs for the purpose. The exercise is useful for some couples who have difﬁ  culty under-
standing each other’s point of view, and may promote better mutual understanding.
A third intervention in session is the use of ‘ sculpting ’ , in which

A third intervention in session is the use of ‘ sculpting ’ , in which 
the partners position themselves and each other wordlessly in a kind of tableau to express some aspects of the relationship. For example, a wife who feels herself excluded from her husband’s life may place him looking away from her, while her husband might place the two arm-in-arm and facing the same way. Neither posi-tion would represent the objective truth, but each would gain some understanding of the views of the other. The different views could also be the subject for discussion in session or during ‘homework’ . As with reversed role play, sculpting, with the accompanying ‘experiential’ insight, can be useful in those couples where there is little understanding of the other’s point of view.
(d) Timetables and tasks

These are perhaps the most frequently used of our interventions. They are always given as part of the ‘homework’ at the end of the session, and may be of a behavioural nature or more systemic. Systems tasks are usually used for behaviour which is thought of as being out of control. Thus, they may be used in a couple where there is a jealous partner: this partner would be asked to raise his or her doubts about the other’s ﬁ  delity, but only at a speciﬁ  ed 
time each day and for a limited period (e.g. half an hour). If the topic comes up at any other time, they are asked to postpone any discussion till the appointed time. This can be frustrating for the jealous partner, although he or she will perhaps be reassured that the other will give the topic his or her full attention at the set 
time: but for the other partner it can come as a great relief that the 
issue of jealousy is at last under some sort of control, even in this 
simple form.

A timetabled task may be used in other situations, for example, 
when one partner has a series of complaints which the other is rejecting. The couple can again be asked to discuss the issue only

1377
at certain times and for a limited duration. The advantage of a 
timetable under these circumstances is that the therapist does not have to adjudicate as to who is right or wrong in the content of the argument, but simply deals with the process of arguing by asking the couple to raise their legitimate complaints at home at an appro-priate but limited time.
Another frequently used timetable is the ‘talk’ timetable, in which 
a couple who do not communicate very often are asked to set a time each day or evening when they can get together for a discus-sion about the day’s events. In cases where there are difﬁ  culties with 
empathy, it may be useful in addition to ask each partner at the daily talk session to repeat back what the other one has said to reassure the other that they have understood what is meant.
One situation which responds particularly well to timetabling is

One situation which responds particularly well to timetabling is 
where the male partner is very keen on sex and the female (while not having a sexual dysfunction as such) is much less enthusiastic. Here the partners are encouraged to reach a compromise on the agreed frequency at which sexual relations might occur, and then they agree on a suitable timetable. The day of the week has to be ﬁ xed in advance, since if this is not done the usual arguments will

ensue as to whether sex should take place that night, and they are also asked to make the chosen night something special, with perhaps a dinner and the telephone disconnected. If, however, the enthusiastic partner suggests sex on another night, the other can simply remind him that it has been arranged and that they should stick to the arrangement. This remedy may seem somewhat crude, and it is often simply a temporary measure. However, it can be said to have virtually saved some relationships, because it takes the heat out of the sexual conﬂ  ict which could otherwise lead to divorce, 
and its use can open up the discussions in subsequent sessions to include non-sexual topics which would otherwise be pushed out by the sexual issue.
It should be mentioned here that many relationship problems 
have a sexual and a general dimension. When the sexual difﬁ  culty is

have a sexual and a general dimension. When the sexual difﬁ  culty is 
motivational rather than dysfunctional, it is often most productive to deal with it in couple relationship therapy either alone or in combination with psychosexual therapy. In such a case it is quite appropriate to suggest techniques such as the Masters and Johnson ‘sensate focusing’
(26) in addition to the couple therapy approaches 
already mentioned.
(e) Paradoxical interventions
Paradox is a relatively infrequently used option in couple therapy (Fig. 6.3.7.1), and is brought in when other methods are ineffective or where the couple relationship seems so rigid that no other intervention can be used. The rationale for paradox depends on a systemic hypothesis which states that the homeostatic forces in the system may be so strong that no straightforward intervention will alter it. All systems tend towards a resistance to change, but in

some the resistance is maintained by powerful forces which them-
selves seem to be informed by extreme anxiety.
(14) In these couples 
or families the only intervention likely to succeed in changing the 
system is one which prohibits change, but for unacceptable reasons. 
Although the above explanation is somewhat unsatisfactory, 
paradox remains in practice a technique which can unlock an 
otherwise stuck relationship and get the couple back on course for 
continued therapy.
Paradox is always applied with care and in a sympathetic manner. 
A common form is to ‘prescribe the symptom’ , that is to advise the couple that it is best ‘for the time being’ to persist with both the behaviour complained of and the reciprocal behaviour in the other partner. The reason given for this conclusion is a plausible, but 
challenging and perhaps unacceptable, explanation based on sys-
temic understanding of the relationship.
In using paradox the therapist should think in four stages. First,

In using paradox the therapist should think in four stages. First, 
there should be a positive connotation of the ‘symptom’ and the reciprocal behaviour. Secondly, there should be a rehearsal of why they are at present helpful for the couple. Thirdly, a statement should be made of the hypothesized feared consequences if the behaviours were to stop. Fourthly, the symptom and the reciprocal behaviour should be prescribed. A case example may make this process a little clearer.
Case Study:  A couple who presented with depression in the wife

Case Study:  A couple who presented with depression in the wife 
(Edna) and a rather overprotective attitude on the husband, George’s, side were in therapy for some weeks without much prog-ress. Following a session in which the therapist asked many ques-tions of both of them about the circumstances and consequences of the depressive episodes, the paradox was presented as follows. ‘This depression seems in some ways to be quite good for you as a 
couple, because it enables Edna to help George by giving him a role 
in life as her protector. If the depression were to disappear it might be difﬁ  cult for you both to continue your peaceful relationship, 
because the differences between your views and ideals would become very clear and you might argue all the time. So for the time being it is better for Edna to remain depressed and for George to be her spokesman and protector’ .
This intervention led to quite an outburst from the wife, who up

This intervention led to quite an outburst from the wife, who up 
to that time had always been very quiet, and she began to talk of some of the differences of opinion that they had actually had. The husband looked rather disconcerted, and questioned the therapist’s reasoning. In the next two sessions the couple reversed their imbalance to some extent, the wife became more assertive than the husband, and her depression became less severe.
The paradox can thus be a powerful mechanism for change, but 
it must be used with some caution, since an instruction given paradoxically may be taken literally. So it would be inappropriate to include in a paradox any instructions to break the law, to harm oneself or others, or to act irresponsibly. If given as recommended, however, the paradox can unlock a ‘stuck’ system and put the couple on the road to change and improvement.
In a team setting it is probably best to use a ‘split team’  message

In a team setting it is probably best to use a ‘split team’  message 
rather than a paradox as such. This presents the paradox as above, but in the form of an alternative, for example in the form of a dis-agreement between the therapist and the supervising team. ‘I feel that you can carry on with the tasks that I have been giving you, but my team think I am being naïve, and that you really need the depressive symptoms and the overprotection to keep your marriage from falling apart’ . The effect is similar, but the impact is softened somewhat by this technique.
Couple therapy with couples from other cultures
As mentioned above, most western countries are now multi-cultural, and a significant minority of those seeking therapy, especially in urban centres, are from immigrant backgrounds. Probably the most frequently seen in Britain are those of South Asian origin, but Eastern European, African and African- Caribbean 6.3.7 psychotherapy with couples

SECTION 6  treatment methods in psychiatry 1378
couples are also seen quite often. In the USA there are many people 
of Latin American and Oriental backgrounds, and here again these will be more commonly encountered in urban settings. The author’s experience is mainly with South Asians, and the examples will be mainly from this group.
Cultural factors in counselling have been highlighted by 
d’Ardenne and Mahtani,
(27) and include the need for awareness in 
the counsellor that he or she also comes from a speciﬁ  c culture 
which may be just as difﬁ  cult for the client to comprehend as the 
client’s is to the counsellor. They emphasize the need for humility in the face of difference, and the responsibility of the counsellor to check with the clients before making assumptions about their lifestyles and beliefs. Their advice on the use of interpreters is that unofﬁ  cial interpreters, including members of the clients’ own

families, should be discouraged because they are inclined to act as therapists themselves, may translate inaccurately, may ignore cultural differences and may even exploit the clients. It is better to use ofﬁ  cial interpreters, though this may become expensive to the 
treatment unit, and the interpreters themselves may translate inac-curately in accord with what they think the therapist wants to hear. 
Ideally a unit would have multilingual counsellors, but this is not 
always practicable. In practice, it is often possible with a modicum of understanding of the language for a couple relationship thera-pist to carry out therapy in English without an interpreter, but with a little bit of necessary translation by the partner whose English is better.
Little has been written speciﬁ  cally on cultural factors in relation-
ship therapy, but Ahmed and Bhugra
(28) have reviewed the role of

(28) have reviewed the role of 
culture in sexual dysfunctions, and their observations are also relevant to couple therapy. They emphasize the need to adapt the techniques of ‘western’ sex therapy to accommodate the cultural backgrounds of the patients, in particular the gender roles in the culture, and they highlight the risks of ignoring these in therapy.
Couple therapists need to be ﬂ  exible in regard to the aims of 
therapy in these couples, which may be rather different from the typical white British couple, and there may also be limits to the kind of therapeutic change possible. For example, a couple from South Asia may be orientated towards a male dominated marital pattern, and both partners may be reluctant to accept the kind of equal relationship that typical couple therapy would expect. In other cases, the more traditional male partner may be concerned

to retain the traditional dominance, while the (more westernized) 
woman may be demanding equality. Similar problems may arise in couples who come from different cultures, and there are clearly more interracial relationships developing as the cultures become more integrated.
Religious considerations may bring difﬁ  culties to therapy. Strict 
Muslim couples may be reluctant to attend therapy together, par-ticularly with a male therapist, because of the difﬁ  culty of the wife 
talking to a male stranger. Masters and Johnson
(26) found that one 
of the most reliable prognostic factors in their therapy was the neg-ative effect of any strong religious belief on the outcome. It has also been observed that in a sexual dysfunction clinic Asian couples were more likely than white couples to default from therapy, a ﬁ  nd-
ing put down to their pursuit of organic explanations for the prob-lems and educational and language barriers.
(29)

(29)
Similarly African-Caribbean couples will have different aims and 
limitations from white British couples. The father in these families 
may traditionally be more of an absentee, and leave the upbringing of the children to his partner, who becomes the main authority 
ﬁ gure in the family. Again, the therapist must remain aware of pos-
sible differences from his/her own culture, and remember that the key consideration is the wishes and wellbeing of the couple rather than any imposed set of rules derived from theory. In particular it is usually impossible to persuade the man to take a more active role in child care, even when the woman wants this, and their relation-ship will usually remain ‘semi-detached’ .
One particular ‘problem constellation’ which the author has

One particular ‘problem constellation’ which the author has 
seen many times is that of an Englishman married to a North American woman. This should theoretically present no problems, as the language and cultures of both are similar. However, they are divided by the tendency for the British man to be reserved and sometimes resentful and the American woman to be outspoken and critical. Such difﬁ  culties have also been found with couples 
from other disparate backgrounds, such as North American and

from other disparate backgrounds, such as North American and 
Latin American partners, and Southern European and British couples. These differences in outlook can lead to repetitive quar-rels, in which neither partner can understand where the other is coming from, and often there is also a lack of sexual contact between them. In therapy it is usually necessary to explain each partner to the other, using positive terms and helping them to appreciate the cultural differences without condemning the partner. Then they can usually cooperate with reciprocity negotia-tion and communication training.
Although the examples given are mainly of South Asian and

Although the examples given are mainly of South Asian and 
Western couples, the principles for dealing with cross-cultural relationships of all sorts are basically similar. The therapist needs to respect the differences between their culture and his/her own, trying not to impose solutions which are alien to the couple’s own culture. In those cases where they each come from a different back-ground, the general approach is to try to build bridges between them, and use the techniques of behavioural systems therapy to solve their difﬁ  culties.
Efﬁ cacy of couple therapy
The efﬁ  cacy of couple therapy is not an easy topic to discuss. 
Problems arise as to how one should assess efﬁ  cacy, and while most 
authors would agree that a measurable improvement in marital adjustment is a valid measure of improvement, some authors dis miss
that as being too subjective or too superﬁ  cial. On the other hand,

that as being too subjective or too superﬁ  cial. On the other hand, 
to use an objective criterion such as divorce as an outcome variable might be seen as being too strict on the therapy, since divorce happens for many reasons, and it might not actually be a bad out-come in some relationships.
A review of efﬁ  cacy in couple therapy has been carried out by 
Baucom et al.
(30) They did a very thorough search of the literature, 
and made some far-reaching and challenging observations. They comment that the untreated improvement rate is very low in cou-ple problems, and that many of the non-behavioural approaches are of unproven efﬁ  cacy. They conclude however that behavioural 
marital therapy (comparing mean effect size over a series of 17 independent controlled outcome studies) is an efﬁ  cacious and

marital therapy (comparing mean effect size over a series of 17 independent controlled outcome studies) is an efﬁ  cacious and 
speciﬁ  c intervention for marital distress. The improvement is likely 
to last for up to a year after treatment but there is less certainty over longer follow-up periods. The addition of cognitive restructuring to behavioural couple therapy did not add anything to the efﬁ  cacy, 
but the numbers were rather small.

1379
Snyder and Wills(31) evaluated the outcomes of behavioural ver-
sus insight-orientated marital therapy, and found that there was equal improvement in the two conditions, with both being superi-or to waiting list controls. There was, however, a difference at follow-up, with more of those who had had behavioural therapy divorcing than those who had had insight-orientated therapy.
In a controlled study of behavioural versus interpretative couple 
therapy, Crowe
(32) found that both approaches were effective, but 
that the behavioural approach produced results more quickly. The follow-up at 18 months showed both methods to be of lasting efﬁ cacy, with no differences between them at that point.
Another treatment approach, emotion-focused therapy,
(33) has 
produced good results with couples in therapy. As with behavioural couple therapy the couples improved signiﬁ  cantly more than those

(33) has 
produced good results with couples in therapy. As with behavioural couple therapy the couples improved signiﬁ  cantly more than those 
on a waiting list, but this therapy seems less effective in couples with higher levels of distress.
In one of the relatively few studies on the efﬁ  cacy of systems-
orientated couple therapy. Emmelkamp et al .
(34) evaluated the 
effects of behavioural versus systems couple therapy, and conclud-ed that the two approaches had very similar results, but both did better than waiting-list controls.
The London Depression Study
(20) (see above) found that sys-
temic couple therapy produced good improvement not only in terms of the couple satisfaction but also on the depression in the depressed partner. The therapy was also associated with a lower drop-out rate than the antidepressant condition, and was thus more acceptable to the patients and their partners.

Thus, the two components of behavioural–systems couple therapy 
have both been validated by outcome research, although at a much higher level for the behavioural than the systemic. It would be desirable to carry out research on the combined therapy, but this has not yet been done, and the best that can be said is that it is a combination of two probably effective treatment approaches, and therefore likely to be effective.
Training
Training for work with couples using a behavioural–systems approach has been thoroughly reviewed by Crowe and Ridley.
(1)

Training
(1)
It requires an ability in the therapist to understand and use differ-ent approaches, and an ability to adapt ones activity to the needs of the couple. Before beginning to work as a couple therapist the trainee should have a basic understanding of the dynamics of couple and family interaction, the phases of human development, the impact on the individual of life events, sexual function and interaction and the impact of physical illness on couple and family relationships. These can be dealt with in the traditional seminar format, in which the trainee can also learn about theoretical and technical aspects of the approach to couple therapy itself. It is also important in selecting candidates for training to ensure that they have some experience of counselling individuals or of being in a therapeutic role, for example as a nurse or doctor.

In addition to the seminars there are also more active training 
sessions in which the trainee is given the technical skills to carry out therapy. The latter take three main forms: role play, obser-vation, and supervized practice. In role play the trainees are encour-aged to use either an existing couple or a ﬁ  ctional one and role play 
a couple therapy session. Ideally they should each, in different exercises, have the opportunity to play the husband, wife, therapist, and observer in therapy.
(35) This helps both in the development of 
technical skills and in learning to be empathetic to clients through having experienced the client role. In role play the trainee can prac-tise any of the techniques required in therapy, but it is perhaps espe-cially useful in the area of communication training, in which the therapist needs to be alert to the problems shown by the partners and able to apply the appropriate technique smoothly and effectively.

In observation and supervision other aspects of the therapy can 
be taught, especially the more systemic methods such as arguments, reversed role play, and the framing of messages. The trainees move quite quickly from live observation of therapy in the clinic to being ﬁ rstly a co-therapist and then the sole therapist in the session, 
supported and supervised by the trainer and the observation team on the other side of the screen. It is in this activity that trainees begin to display their skills or deﬁ  cits as therapists, and the trainer 
must be able to assess progress at this stage and take remedial action if a trainee does not seem to be working as well as expected.
The ﬁ  eld of couple therapy is a wide and varied one, and there are

The ﬁ  eld of couple therapy is a wide and varied one, and there are 
almost as many different approaches to treatment as in individual psychotherapy. The relatively brief therapeutic method presented here, behavioural systems couple therapy, is an eclectic one, taking techniques from two approaches of proven efﬁ  cacy and combining 
them into a ﬂ  exible and versatile therapy capable of being used 
in a wide variety of presenting problems. These include simple relationship problems, psychosexual problems, and such psychiatric conditions as anxiety, depression, and morbid jealousy. It is rela-tively easy to teach, and although it has not yet been subjected to controlled trials it can be assumed to be no less effective than its component therapies which are both effective. It has recently also been recommended in a package for self-help
(36) with home-

work exercises and theoretical explanations to be used without the intervention of a therapist. There are few contraindications for the therapy, and it can be used both as a therapy in its own right or as an adjunctive therapy in, for example, the treatment of depression, psychosis or sexual dysfunctions. It can thus be a useful addition to the various methods available for the reduction of distress, whether in couples or individuals.
Crowe, M. and Ridley, J. (2000). Therapy with Couples: a behaviouralsystems
approach to marital and sexual problems  (2nd edn.). Blackwells Science, 
Oxford.
Clulow, C. (ed.) (2001). Adult Attachment and Couple Therapy . Brunner
Organizations which provide information about how 
to obtain couple therapy
British Association for Sexual and Relationship Therapy www.basrt.org.uk

British Association for Counselling and Psychotherapy www.bacp.co.ukUnited Kingdom Council for Psychotherapy www.psychotherapy.org.ukInstitute of Family Therapy www.instituteoffamilytherapy.org.ukAmerican Association for Marriage and Family Therapy www.aamft.org
Organizations which provide information on training 
in Sexual and Relationship Therapy
British Association for Sexual and Relationship Therapy www.basrt.org.uk6.3.7 psychotherapy with couples

SECTION 6  treatment methods in psychiatry 1380
Porterbrook Clinic, Shefﬁ  eld (Shefﬁ  eld Hallam University) www.
porterbrookclinic.org.uk
London South Bank University ww.lsbu.ac.uk/psychologyUniversity of Central Lancashire: Lancashire School of Health and 
Postgraduate Medicine www.uclan.ac.uk
Relate Institute, Doncaster www.relate.org.uk
American Association for Marriage and Family Therapy www.aamft.org
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counter–paradox.  Aronson, New Y ork.
15. Segraves, R.T. (1982). Marital therapy: a combined psychodynamic– 
behavioural approach.  Plenum Medical, New Y ork.
16. Weeks, G.R. (1989). Treating couples, the intersystem model of 
the Marriage Council of Philadelphia.  Brunner–Mazel, 
New Y ork.
17. Spinks, S.H. and Birchler, G.R. (1982). Behavioural–systems marita l 
therapy: dealing with resistance. Family Process ,21, 169–85.
18. Berg–Cross, L. (1997). Couples therapy . Sage, Thousand Oaks, CA.
19. Jacobson, N.S. and Margolin, G. (1979). Marital therapy: strategies 
based on social learning and behavioral exchange principles.Brunner–Mazel, New Y ork.
20. Leff, J., Vearnalls, S., Brewin, C.R., et al. (2000) The London depression

20. Leff, J., Vearnalls, S., Brewin, C.R., et al. (2000) The London depression 
intervention trial. Randomized controlled trial of antidepressants v. couple therapy in the treatment and maintenance of people with depression living with a partner: clinical outcome and costs. British 
Journal of Psychiatry ,177, 95–100.
21. De Silva, P . (1997) Jealousy in couple relationships: nature, assessment 
and therapy. Behaviour Research and Therapy ,35, 937–85.
22. McFarlane, W. (2000) Psychoeducational multi-family groups. 
Adaptations and outcomes. In Psychosis: Psychological Approaches 
and their Effectiveness.  (ed. B. Martindale, A. Bateman, M. Crowe 
and F. Margison) Gaskell, London.
23. Crowe, M. (2005) Couples and mental illness. Sexual and Relationship 
Therapy ,19, 309–10.
24. Thibault, J.W. and Kelley, H.H. (1959). The social psychology of groups.
Wiley, New Y ork.

25. Olson, D.H., McCubbin, H.I., Barnes, H., et al. (1983). Families: what 
makes them work.  Sage, Los Angeles, CA.26. Masters, W.M. and Johnson, V .E. (1970). Human sexual inadequacy. 
Little, Brown, Boston, MA.
27. d’Ardenne, P . and Mahtani, A. (1989). Transcultural Counselling in 
Action . Sage, London.
28. Ahmed, K. and Bhugra, D. (2007). The role of culture in sexual 
dysfunction. In Psychiatry: Sexual Disorders and Psychosexual Therapy .
(ed M.Crowe). Medicine Publishing (Elsevier), London.
29. Bhui, K. (1998). Psychosexual care in a multi-ethnic society. Journal of 
Social Medicine ,91, 141–3.
30. Baucom, D.H., Shoham, V ., Mueser, K.T., et al. (1998). Empirically

30. Baucom, D.H., Shoham, V ., Mueser, K.T., et al. (1998). Empirically 
supported couple and family interventions for marital distress and adult mental health problems. Journal of Consulting and Clinical 
Psychology ,66, 53–88.
31. Snyder, D.K. and Wills, R.M. (1989). Behavioural versus insight 
orientated marital therapy: effects on individual and interpersonal functioning. Journal of Consulting and Clinical Psychology ,57, 39–46.
32. Crowe, M.J. (1978). Conjoint marital therapy: a controlled outcome 
study. Psychological Medicine ,8, 623–36.
33. Johnson, S.M. and Greenberg, L.S. (1985). Differential effects of 
experiential and problem–solving interventions in resolving marital conﬂ  ict. Journal of Consulting and Clinical Psychology ,53, 175–84.
34. Emmelkamp, P .M.G., van der Helm, M., MacGillavry, D., et al. (1984).

34. Emmelkamp, P .M.G., van der Helm, M., MacGillavry, D., et al. (1984). 
Marital therapy with clinically distressed couples: a comparative evaluation of system–theoretic, contingency contracting and communication skill approaches. In Marital interaction: analysis and 
modiﬁ  cation (ed. K. Hahlweg and N. Jacobson), pp. 36–52.Guilford 
35. van Ments, M. (1983). The effective use of role–play. A handbook for 
teachers and trainers.  Kogan Page, London.
36. Crowe, M. (2005) Overcoming Relationship Problems. Constable 
Robinson, London.
6.3.8 Family therapy in the 
adult psychiatric setting
The term ‘family therapy’ covers a range of approaches. At one 
extreme, it is a method which seeks to help an individual patient. At the other extreme, the focus is on the relationships between peo-ple; according to this view psychopathology reﬂ  ects recurring,

problematic interactive patterns among family members. Midway between the two positions is one that views the family as acting potentially either as a resource or a liability for an identiﬁ  ed patient. 
In this chapter, we cover the spectrum but conﬁ  ne ourselves to the 
adult psychiatric setting.
A historical and theoretical context
The family has long been recognized as a core aspect of social orga-nization. The folklore of all cultures emphasize the family’s role to mould the character of its members. In the past 150 years academic disciplines, such as anthropology and sociology, have studied the various forms of family structure found in different cultures, and at different times. Since the 1960s, psychiatry has also developed a clinical and research interest in the family beyond that of genetics.
Scattered through Freud’s writings are interesting comments 
about marital and family relationships and their possible roles in

1381
both individual normal and abnormal development.(1) His descrip-
tion of unconscious processes like introjection, projection, and identiﬁ  cation illuminate how individual experiences may be trans-
mitted across generations. In 1921, J.C. Flugel published the ﬁ  rst 
comprehensive psychoanalytic account of family relationships.
(2)
Inﬂ uenced by Anna Freud, Melanie Klein, and Donald Winnicott, 
the child guidance movement in Britain, mainly consisting of social workers, devised a model of one therapist working with the disturbed child and another with the mother. The two clinicians then collaborated in order to appreciate how the mother’s anxieties distorted her perception and handling of her child, leading to developmental difﬁ  culties.
Proliferation of theoretical schools
Psychoanalytic and related approaches
Things took a different turn in the United States where Nathan 
Ackerman(3) began in the 1950s to treat families with a disturbed

Ackerman(3) began in the 1950s to treat families with a disturbed 
child, using psychodynamic principles. An interest in working with two or more generations arose concurrently with ‘transgeneration al’-
oriented family analysts using object–relations concepts. Thus, Murray Bowen
(4) noted that the capacity of psychotic children to 
differentiate from their families, while still retaining a sense of age-appropriate belonging, was impaired by the effects of unre-solved losses and other trauma in parental and grandparental gen-erations. He also devised the genogram, a schematic depiction of family structure, with a notation for notable events; this remains a standard part of family assessment (see below).
Boszormenyi-Nagy and Spark
(5) similarly addressed the trans-

generational theme, describing how relationships were organized around a ledger of entitlements and obligations, which conferred on each family member a sense of justice or injustice about their situation. This, in turn, reﬂ  ected childhood experiences of neglect 
or sacriﬁ  ces made on another relative’s behalf for which redress 
was sought in adult life.
Systems-oriented (see later)
Bowen(4) also introduced the principles of ‘systems theory’ into 
family therapy. A system is deﬁ  ned as a set of interrelated elements 
that function as a unity within a particular environment and where the whole is larger than the sum of the parts. ‘General systems theory’ , propounded in the 1940s by a German biologist,
(6)

(6)
contains among its key concepts the place of hierarchy and the emergence of new features in the system as it transforms itself, necessarily, from one level of organization to another. A family is an example of a partially open system that interacts with both its biological and socio-cultural environments and changes over time to accommodate developments such as the advent of a ﬁ  rst child or 
the death of a grandparent.
Working with delinquent youth, Salvador Minuchin recognized

Working with delinquent youth, Salvador Minuchin recognized 
the relevance of systems thinking. The youngsters often came from poor, emotionally deprived families, headed by a demoralized single parent (usually the mother) who alternated between exces-sive discipline and helpless delegation of responsibilities to a child or to her own critical mother. Since these families were beyond the 
reach of conventional ‘talking’ therapies, Minuchin applied action-
oriented techniques which enabled him to ‘join’ the family and to re-establish an adaptive hierarchy and effective boundaries between subsystems (marital, parent–child, siblings).Later, treating ‘psychosomatic families’ where the problem was a

child or adolescent suffering from anorexia nervosa, unstable diabetes or asthma, Minuchin and his colleagues noted that these families, while intact and articulate, were often enmeshed. Members avoided challenging the apparent sense of family unity. Typically, marital conﬂ  ict was detoured through the symptomatic child, 
resulting in maladaptive coalitions between parent and child (sometimes between grandparent and child) and the involvement of third parties (e.g. helping agencies) in family life; loss of hierar-chy and boundaries ensued. Because words were used to avoid change in these well-educated families, non-verbal strategies were devised to face unspoken fears of conﬂ  ict and change.
(7)
Jay Haley’s ‘strategic therapy’(8) combined features of Minuchin’s 
model with ideas of Milton Erickson whose techniques had skilfully exploited the notion that a covert message lurks behind explicit communication, which deﬁ  nes the power relationship

model with ideas of Milton Erickson whose techniques had skilfully exploited the notion that a covert message lurks behind explicit communication, which deﬁ  nes the power relationship 
between family members. Related theoretical developments took place in Palo Alto, California in the 1950s, where a group of clini-cians, together with the anthropologist Gregory Bateson,
(9)
observed that implicit in communication were tacit, non-verbal ‘meta-communications’ which deﬁ  ned the ties between partici-
pants. A contradictory quality between these two levels of commu-nication—in which messages carried persuasive, moral, or coercive force for the recipient—formed part of what they called a ‘double-bind’; this form of entrapment was proposed, albeit erroneously, as a possible basis for the formal thought disorder found in schizophrenia.
(10, 11)
(a) Systems-oriented models: further developments

(10, 11)
All the above system-oriented views assume that family functioning can be objectively studied. However, therapists are not value-free and may actively orchestrate changes in accordance with their preferred theoretical model; neglected in these circumstances are therapists’ biases and their inﬂ  uence.
This tendency probably reﬂ  ected the determination of family 
therapists to distance themselves from psychoanalytical theory; but it also led them to neglect the family’s past history and changes through the lifecycle, including the relevance of traumatic events.
In response to this criticism there was a shift away from a prob-
lem-focused approach, which had typiﬁ  ed most communication-
based views of psychopathology. The so-called Milan school
(12)

(12)
(see course of therapy below), whose founders were psychoanalysts, launched profound conceptual changes in how to approach the family, particularly in interviewing them. Another innovation was the participation of observers behind a one-way screen whose task was to offer hypotheses about the family-plus-therapist system to the protagonists.
A Norwegian group
(13) took the idea one step further by devel-
oping the ‘reﬂ  ecting team dialogue’ . Here, following a session, the 
family could observe the therapeutic team discussing their problems and possible causes, and what factors might have prompted them to seek certain remedies—especially those they had persevered with despite the clear lack of effectiveness.
(b) Post-modern developments

Family therapists also began to ask whether families might be hampered from trying out new ways to solve their difﬁ  culties 
because of the ways they themselves had interpreted their past experiences or unwittingly absorbed the explanatory narratives of external ‘experts’ or society at large.6.3.8 family therapy in the adult psychiatric setting

SECTION 6  treatment methods in psychiatry 1382
This led to a shift from considering the family as a system deﬁ  ned 
by its organizational structure to a linguistic-based one. According to this view the narrative a family relates about themselves is a means to integrate in speciﬁ  c ways their past experience and its 
significance. Other ‘stories’ are excluded from consideration. For instance, when a family with an ill member talk to health pro-fessionals, the conversations inevitably revolve around problems (a problem-saturated description). The family ignore times when problems were absent or minimal, or when they were conﬁ  ned to 
manageable proportions. A different story might be told if they were to examine the factors that could have led, or still lead, to better outcomes than those currently deemed pathological.
Several narrative-based approaches apply these concepts.
(14–16)

(14–16)
Philosophically, they align themselves with post-modernism, a movement which challenges the idea that there is a fundamental truth or grand theory known only by the expert.
(c) Criticism of systems approaches
Many criticisms have been levelled at systems-based approaches, these include:
◆ disregard of the subjective experiences of family members
◆ neglect of the family’s history
◆ inattention to unconscious motives in interpersonal behaviour
◆ not addressing the issue of unequal power in a family, particu-
larly violence against women and child abuse, and
◆ ignoring various forms of injustice based on societal attitudes 
regarding gender, ethnicity, and class.
This critique has led to integrating systems-oriented and psycho-
analytic concepts, particularly those derived from object–relations theory.
(17–20) Specific disorders such as schizophrenia(21) and 
anorexia nervosa(22) have been targeted. Another noteworthy

anorexia nervosa(22) have been targeted. Another noteworthy 
variant of integration is Byng-Hall’s(23) synthesis of attachment 
theory, systems-thinking, and a narrative approach.
Another criticism of systems-oriented approaches is minimizing 
the impact of material reality, such as physical handicap, or bio-logical factors, in the causation of mental illness, as well as socio-political phenomena like unemployment, racism, and poverty. These are obviously not merely the result of social constructions or linguistic games and the distress they may inﬂ  ict on people are 
potentially considerable.
The ‘psycho-educational’ approach and ‘family crisis inter-
vention’ have arisen in the context of the burden that severe mental illness, particularly schizophrenia, places on the family and the potential for members to inﬂ  uence dramatically the course of the

condition. This has led to a series of family interventions:
◆ educating the family about the nature, cause, course, and treat-
ment of schizophrenia
◆ providing the family with opportunities to discuss their difﬁ  cul-
ties in caring for the patient, and to devise pertinent strategies
◆ clarifying the role of conﬂ  ict, not only about the illness but also 
about other relational issues
◆ regularly evaluating the impact of the illness on the family, both 
individually and collectively
◆ helping to resolve other conﬂ  icts possibly aggravated by the 
demands of caring for a enduringly ill person.This type of work may be done with a single family or with

demands of caring for a enduringly ill person.This type of work may be done with a single family or with 
several families meeting together, known as Multiple-Family Group Treatment (MFGT). The latter has emerged as a powerful adjunct to conventional individual-based treatment of schizophrenia, bipolar disorder, major depression, obsessive-compulsive disorder, somatization disorder, and an array of chronic medical conditions. Good results have been achieved in reducing the relapse rate, duration, and frequency of hospitalization and in boosting compli-ance with medication.
(24) Family crisis intervention, initially 
devised for families with a schizophrenic relative but since applied to other clinical states, operates on the premise that deterioration or a request by the family to hospitalize a member may reﬂ  ect

change in a previously stable pattern of family functioning. Convening an emergency meeting with the patient, spouse, and other key family members may help to avoid admission. Social and institutional forces outside the family often contribute to a crisis, and may precipitate a psychotic episode in a vulnerable member. The ‘open dialogue’ model of family crisis interviewing, developed in Finland, fosters discussion about such forces, using concepts and techniques derived from, inter alia , the Milan school, narrative 
approaches, and psychodynamic thinking; this integrated perspec-tive has much potential.
(25)

(25)
A measure of controversy has dogged the issue of what constitutes the indications for family therapy. Pioneering practitioners claimed, somewhat overzealously, that their methods were suited to most conditions. A more balanced view since the mid-1990s encompasses a consensus that considering the systemic context is advantageous in assessing and treating any psychiatric problem. However, it does not follow that family therapy is the treatment of choice (or even indicated).
Family therapy, it should be stressed, does not constitute a 
unitary approach, with one principal purpose. The diversity of theoretical models we have alluded to above, with their correspond-ing techniques, should make this obvious. Regrettably, attempts to link indications to speciﬁ  c models have contributed little to the 
ﬁ eld.
It has also become clear that DSM or ICD diagnoses do not serve

ﬁ eld.
It has also become clear that DSM or ICD diagnoses do not serve 
well as a basis for determining indications for family interventions. DSM has a minuscule section, the V diagnoses, covering ‘relational problems’; these are limited in scope and not elaborated upon.
(26)
We are only informed that the problem in relating can involve a couple, a parent, and child, siblings, or ‘not otherwise speciﬁ  ed’ . 
ICD neglects this relational area entirely.
In mapping out indications, we need to avoid blurring family 
assessment and family therapy. A patient’s family may be recruited in order to gain more knowledge about diagnosis and treatment. This does not necessarily lead to family therapy. Indeed, it may point to marital therapy or to long-term supportive therapy. Thus, we need to distinguish carefully between an assessment family interview and family therapy per se .
A typology of family psychopathology, which might allow us to

A typology of family psychopathology, which might allow us to 
differentiate one pattern of dysfunction from another and so map out corresponding interventions, remains elusive. Empirical evi-dence is inconclusive and clinical consensus lacking. An inherent 
difﬁ culty is in selecting dimensions of family functioning central to 
creating a typology.
(27) Communication, cohesiveness, adaptability,

1383
boundaries between family members and subgroups, and level of 
conﬂ  ict are a few of the contenders offered (see our own classiﬁ  ca-
tion below).
There are no clear correlates between conventional diagnoses 
and family type. Efforts to establish links, such as an anorexia nervosa family
(28) or a psychosomatic family(29) have not been 
fruitful. Similarly, investigations into the family and schizophrenia have yielded no durable results.
(4,10) Clinicians and researchers 
have reluctantly accepted that models of effective family-based treatment for mental illness may not necessarily follow an under-standing of the apparent causes of a condition in terms of observed disturbances in family relating. This complex matter is helpfully reviewed by Eisler regarding studies of the treatment of anorexia nervosa, but has implications for the entire ﬁ  eld.
(30)
What follows is our attempt to distil clinical and theoretical 
contributions.(31) Given the considerable overlap in clinical

(30)
contributions.(31) Given the considerable overlap in clinical 
practice, categories are not mutually exclusive; and a family may require family therapy based on more than one indication. We should stress that family dysfunction is obvious in certain clini-cal situations and covert in others, often being concealed by a speciﬁ  c member’s clinical presentation. Six categories emerge:
1 The problem manifests in explicit family terms and the therapist 
readily notes the family’s dysfunction. For example, a marital conﬂ  ict dominates, with repercussions for the children; or ten-
sion between parents and an adolescent child dislocates family life with everyone ensnared in conﬂ  ict. In these situations the 
family is the target of intervention by dint of its clear dysfunc-tional pattern, and family therapy undoubtedly is the treatment of choice.
2 The family has experienced a disruptive life event which has led

2 The family has experienced a disruptive life event which has led 
to its dysfunction. These events are either predictable or acciden-tal and include, for instance, suicidal death, ﬁ  nancial embarrass-
ment, diagnosis of a serious physical illness, and the unexpected departure of a child from home. Any family stability that pre-vailed previously has been disturbed; the ensuing disequilibrium becomes associated with family dysfunction and/or the develop-ment of symptoms in one or more members. Family efforts to rectify the situation may inadvertently aggravate it.
3 Continuing, demanding circumstances in a family are of such 
a magnitude as to lead to ineffective adjustment. The family’s resources may be stretched to the hilt; external sources of support may be scanty or unavailable. Typical situations are chronic physical illness, persistent or recurrent psychiatric illness, and the presence of a frail elderly member.
4 An identiﬁ  ed patient may have become symptomatic in the

4 An identiﬁ  ed patient may have become symptomatic in the 
context of a dysfunctional family; symptoms are in fact an expression of that dysfunction. Depression in a mother, an eating problem in a daughter, alcohol misuse in a father, through family assessment, are adjudged to reﬂ  ect underlying family 
5 A family member is diagnosed with a conventional condition 
such as schizophrenia, agoraphobia, obsessive-compulsive disorder, or depression; the complications are the adverse rever-berations within the family stemming from that diagnosis. For example, the son with schizophrenia taxes his parents in ways that exceed their ‘problem-solving’ capacity; an agoraphobic woman insists on the constant company of her husband in activities of daily living; a recurrently depressed mother comes to

rely on the support of her eldest daughter. In these circumstanc-es, members begin to respond maladaptively to the diagnosed relative, which paves the way for a deterioration of her condition, manifest as an enduring or relapsing course.
6 Thoroughly disorganized families, buffeted by many problems, 
are viewed as the principal target of help. This is apposite, even though, for instance, one member abuses drugs, another is prone to violence, and a third manifests antisocial behaviour. Regarding the family as the core dysfunctional unit is the rationale rather than a focus on each member’s individual problems.
T o reiterate, family therapy may not be the only treatment indi-

cated. Thus, in helping a disturbed family struggling to deal with a schizophrenic member, supportive therapy and medication for the patient are usually as pertinent as any family treatment. Similarly, an indication for family therapy does not negate the possible use of another psychological approach for one or more family members. For instance, an adolescent striving to separate and individuate 
may beneﬁ  t from individual therapy following family treatment 
(or in parallel with it), while his parents may require a separate programme to focus on their sexual relationship.
These are self-evident and therefore mentioned only brieﬂ  y.
1 The family is unavailable because of geographical dispersal or 
death.
2 Shared motivation for change is lacking. One or more members 
may wish to participate, but their chances of beneﬁ  ting from a

death.
may wish to participate, but their chances of beneﬁ  ting from a 
family approach are likely to be less than if committing them-selves to individual therapy. We need to distinguish here between poor motivation and ambivalence; in the latter, the assessor teas-es out factors that underlie it and may encourage the family to engage.
3 The level of family disturbance is so severe or long-standing, 
or both, that a family approach seems futile, according to the best possible clinical judgement. For example, a family that has fought bitterly and incessantly for years is unlikely to engage in the constructive purpose of exploring their patterns of functioning.
4 Family equilibrium is so precarious that the inevitable 
turbulence
(32) arising from family therapy is likely to lead to

(32) arising from family therapy is likely to lead to 
decompensation of one or more members; for example, a sexu-ally abused adult may do better in individual therapy than by confronting the abusing relative.
5 The patient is too incapacitated to withstand the demands of 
family therapy. Someone in the midst of a psychotic episode or 
buffeted by severe melancholia is too affected by the illness to 
engage in family work.
6 An identiﬁ  ed patient acknowledges family factors in the evolu-
tion of his problem, but seeks the privacy of individual therapy to explore it, at least initially. For example, a university student struggling to achieve a coherent sense of identity may beneﬁ  t 
more from her individual pursuit of self-understanding. Such an approach does not negate an attempt to understand the contri-bution of family factors to the problem.6.3.8 family therapy in the adult psychiatric setting

SECTION 6  treatment methods in psychiatry 1384
Family assessment, an extension of individual psychiatric assess-
ment, adds a broader context to the formulation. The range and 
pace of the enquiry depends on the speciﬁ  cs of the case. Its phases 
are history from the patient, a provisional formulation concerning 
the relevance of the family, an interview with one or more mem-
bers, and a revised formulation. In some cases, it is clear from the 
outset that the problem resides in the family group, thus rendering 
the phases below superﬂ  uous.
History from the patient
The most effective way to obtain a family history is by constructing 
a family tree. Apart from showing the structure, it allows relevant 
information about noteworthy life events and a range of family 
features to be added. Scrutiny of the tree also provides a source 
of issues warranting exploration and, eventually, the potential for 
formulating hypotheses.

Personal details such as age, date of birth and death, occupation, 
education, and illness are recorded for each member, as well as 
critical family events (for example, migration, crucial relationship 
changes, notable losses, and achievements), and the quality of 
relationships. For an excellent discussion of the family tree—its 
construction, interpretation, and clinical uses—see McGoldrick 
and Gerson.(33) (See Fig 6.3.8.1 for genogram conventions.)
Useful principles are to work from the presenting clinical 
problem to the broader context, from the current situation to its 
historical origins and evolution, from ‘facts’ to inferences, and from 
non-threatening to more sensitive themes.
Questions are best preceded by a statement such as: ‘In order to 
understand your problems better I need to know something of

understand your problems better I need to know something of 
your background and your current situation’ . This can be enriched 
by questions that allude to interactive patterns: ‘Who knows about the problem? How does each of them see it? Has anyone else in the 
family faced similar problems? Who have you found most helpful 
and least helpful so far? What do they think needs to be done’ . 
Attitudes of family members can be thus explored and light shed 
on the clinical picture.
The presenting problem and changes in the family
Questions to understand the current context include: ‘What has 
been happening recently in the family? Have there been any changes 
(e.g. births, deaths, illness, losses). Has your relationship with family 
members changed? Have relationships in the family altered?’
The wider family context

A broader enquiry ﬂ  ows logically in terms of other family members 
to be considered, and in the time span of the family’s history. Other 
signiﬁ  cant ﬁ  gures, which may include caregivers and professionals, 
should not be forgotten.
Apart from information about the extended family’s structure, 
questions about their response to major events can be posed: for 
example, ‘How did the family react when your grandmother died? 
Who took it the hardest? How did migration affect your parents?’
Relationships are explored at all levels, covering those between 
the patient and other members and between these other members. 
Conﬂ  icted ties are particularly illuminating. Understanding who 
takes what ‘roles’ is also useful: ‘Who tends to take care of others? 
Who needs most care? Who tends to be the most sensitive to what

Who needs most care? Who tends to be the most sensitive to what 
is going on in the family?’ Asking direct questions about members 
is informative, but a better strategy is to seek the patient’s views 
about their beliefs and feelings and to look for differences between 
members: ‘What worries your mother most about your problem? 
What worries your father most?’ Several lines of enquiry may reveal 
differences.
Fig. 6.3.8.1 Genogram conventions.

1385
◆ Pursuing sequential interactions: ‘What does your father do 
when you say your depressions are dreadful? How does your mother respond when your father advises you to pull up your socks? How do you react when she contradicts him?
◆ ‘Ranking’ responses: ‘Everyone is worried that you may harm 
yourself.Who worries most? Who is most likely to do something when you talk about suicide?’
◆ Looking for relational changes since the problem: ‘Does your 
husband spend more or less time with you since your difﬁ  culties 
began? Has he become closer or more distant from your daughter?’
◆ Hypothetical questions dealing with imagined situations: ‘How 
do you think your relationship with your wife will change if you don’t improve? Who would be most likely to notice that you were getting better?’
Triadic questions help to gain information about relationships

Triadic questions help to gain information about relationships 
which go beyond pairs; for example: ‘How do you see your rela-tionship with your mother? How does your father see that relation-ship? How would your mother react to what you have told me if she were here today?’
Making a provisional formulation
Two questions arise from the above interview—how does the family typically function and are there any family features relevant to the patient’s problems?
(a) How does the family typically function?
A schema to organize ideas about family functioning builds from simple to complex observations: structure, changes, relationships, interaction, and the way in which the family works as a whole.
◆ The family tree will reveal the many family structures possible—
single-parented, divorced, remarried, siblings with large age gaps, adoptees. Unusual conﬁ  gurations invite conjecture about inherent 
◆ Data will be obtained about notable family changes and events;

◆ Data will be obtained about notable family changes and events; 
the timing of predictable transitions is pertinent. Have external events coincided with these transitions (times at which the family may be more vulnerable)? How has the family met such changes?
◆ Relationships refer to how members interact with one another. 
What is the degree of closeness and emotional quality (e.g. warm, tense, rivalrous, hostile)? Major conﬂ  icts may be noted, as may 
be overly intense relationships.
◆ Particular interactive patterns may become apparent which go 
beyond pairs. Triadic relationships are more revealing about how a family functions overall. A third person is often integral to deﬁ  ning the relationship between another pair. A conﬂ  ict, for 
instance, may be re-routed through the third person, preventing direct resolution. A child may act in coalition with one parent against the other or with a grandparent against a parent.

◆ At a higher level of abstraction, the clinician notes how the family 
works as a whole. Particular patterns (possibly a series of triads) may emerge that may have recurred across generations. For exam-ple, mothers and eldest sons have fused relationships, with fathers excluded, while daughters and mothers-in-law are in conﬂ  ict.Idiosyncratic shared beliefs may be discerned, explaining much 
of the way the family does things. ‘Rules’ governing members’ behaviour towards one another or to the outside world may ﬂ  ow 
from these beliefs. For example, a family may hold that ‘Y ou can only trust your own family; the outside world is always dangerous’; they may therefore avoid conﬂ  ict at any cost, and prohibit seeking 
external support.
Evidence of family difﬁ  culties may be found at each of these

Evidence of family difﬁ  culties may be found at each of these 
ﬁ ve levels. If they are, the question arises whether these do or do 
not relate to the patient’s problems.
(b) Are family factors involved in the patient’s problems?
Links between family functioning and the patient’s problems take various forms, but the following categories cover most situations:
◆ the family as reactive
◆ the family as a resource, and
◆ the family in problem maintenance
Often, more than one will apply.
The family as reactive
The patient’s illness, or its exacerbation, may have occurred at a 
time of family upheaval. While the precipitant for the upheaval may have been inherent in the illness itself, an escalating combina-tion of the two may pertain. The illness may have occurred in the face of family stress; it pressurizes the family all the more, and this in turn exacerbates the illness.
The family as a resource

The family may be well placed to assist in treatment. This may be as straightforward as supervising medication, ensuring clinic atten-dance, and detecting early signs of relapse, or providing a home environment that promotes and maintains recovery. The family may also call on friends and agencies, professional or voluntary, to offer support.
The family in problem maintenance
Interactions revolving around the patient’s illness may act to maintain it.
1 First, the illness becomes a way of ‘solving’ a family problem, the 
best that can be achieved. For example, anorexia nervosa in a teenager due to attend a distant university may lead to her aban-doning this plan since she feels unable to care for herself. Were she to leave, parental conﬂ  ict would become more exposed and 
her mother, with whom the patient is in coalition against her father, would ﬁ  nd herself unsupported. The illness therefore

her mother, with whom the patient is in coalition against her father, would ﬁ  nd herself unsupported. The illness therefore 
keeps the patient at home and enmeshed in the parental relation-ship, and also provides a focus for shared concerns and an osten-sible sense of unity.
2 Maintenance of the illness does not solve a family problem but 
may have done so in the past. An interactive pattern persists even though it lacks utility. In the previous example, the father’s mother died 9 months later. His wife subsequently expressed feelings of closeness which he had not experienced for years; their relationship gradually improved. Both parents, however, continued to treat their daughter as incapable of achieving 6.3.8 family therapy in the adult psychiatric setting

SECTION 6  treatment methods in psychiatry 1386
autonomy, reinforcing her own uncertainty about coping inde-
pendently if she were to recover.
3 Persistence of illness reflects a perception by the family of 
themselves and their problems, to which they are bound by the persuasive power of the narrative they have shaped for them-
selves. This often stems from the health care professional’s 
explanatory schema.
Interview with key informants
The clinician will by now have made an initial assessment of the patient’s problems and of the family context. The next step is an interview with one or more informants, usually family members, to corroborate the story, to ﬁ  ll in gaps, to determine inﬂ  uences 
impinging on the patient, and to recruit others to help. A family meeting is most effective to accomplish these goals.
Implementing the session may prove difﬁ  cult since the patient

Implementing the session may prove difﬁ  cult since the patient 
may oppose it for all sorts of reasons: symptoms have been kept secret, he regards it as unfair to burden others, he is ashamed of seeing a psychiatrist, he is fearful the family will be blamed, he is suspicious of them, and so forth. These concerns need ventilating, particularly if the family context is pivotal and it is likely that treat-ment will be enhanced by their involvement. The patient will agree in most cases. Where the safety of the patient or others is threat-ened, refusal may be overridden on ethical grounds. Otherwise, refusal must be respected. A family session can be suggested again after a more trusting relationship has been established.
Who should be seen depends on the purpose of the interview;

Who should be seen depends on the purpose of the interview; 
generally, all those living in the household are likely to be affected by the patient’s illness. The more family factors pertain, the more desirable the attendance by all. The patient’s views are sought since he will provide insight into the members he deems crucial to his ‘story’ .
The family interview
Much information will have been garnered by the time the family is seen. The clinician should consider any biases that may have inﬁ  l-
trated her thinking about the family, and how best to avoid being 
drawn into alliances. A non-judgemental stance is paramount.
Introductions are made in the initial phase. Names and preferred 
modes of address are clariﬁ  ed. The clinician then explains the 
meeting’s purpose, details of which may well inﬂ  uence future par-
ticipation. She invites everyone to share views about the nature and effects of problems they face.
The clinician has an idea about how the patient’s problems relate

The clinician has an idea about how the patient’s problems relate 
to family function, and can test it out by asking probing questions and observing interactions. This is kept to herself since it is unhelp-ful for a hypothesis to be offered prematurely. Instead, details about everyday events are sought and inferences drawn later. For example, rather than focusing on ‘closeness’ , questions can be asked about time spent together, whether intimate experiences are shared, who helps with family tasks, and so on.
Triadic relationships can be scrutinized both through questioning 
(what does A do when B says this to C?) and observation (what 
does A do when B and C reveal tensions?). The scope for such ‘circular’ questioning (a method ushered in by the Milan school) is 
enhanced if several members participate. A third person may be

enhanced if several members participate. A third person may be 
asked to comment on what two others convey to each other when a particular event occurs. This strategy of not posing questions to which the family may have stereotypical responses challenges them 
to think about their relationships in a fresh way.
Information is elicited that elaborates the family tree. 
Observations may be made concerning family structure and func-tioning; for example, who makes decisions, who controls others and in what areas, the quality of speciﬁ  c dyadic relationships, 
conﬂ  ict, alliances, how clearly people communicate and how they 
solve problems. The discussion then extends to all spheres of family 
life: beliefs, traditions, rules, and values.
Throughout the interview the clinician afﬁ  rms the experiences

Throughout the interview the clinician afﬁ  rms the experiences 
of all family members. Concerns are attended to and the members’ strengths and efforts acknowledged.
The interview concludes with a summary of what has emerged. 
The clinician may wish to continue the assessment or recommend family therapy. If the latter, an explanation of its aim and rationale is then given.
Arrangements are made for a follow-up session, purportedly the 
launch of family therapy per se , but in essence a continuation of 
‘work’ in progress.
Revised formulation
Since new information becomes available at each point, the initial formulation is revised as necessary.
Five observational levels —of structure, transitions, relationships,

Five observational levels —of structure, transitions, relationships, 
patterns of interaction, and global functioning—are re-examined in terms of the family as reactive, resourceful, or problem-maintaining. We now turn to the course of family therapy.
The course of therapy
With a family approach agreed upon, therapy begins. However, when a family is referred as a group on the premise that the prob-lem is inherently a family one, it is made explicit that the initial stage incorporates assessment.
Given the plethora of ‘schools’ of family therapy it would be 
laborious to chart the course of treatment based on each. We shall focus on the Milan approach,
(12) but stress that it has undergone 
reﬁ nements. Our account highlights core features but ﬁ  rst we com-
ment brieﬂ  y on the different roles the therapist may assume.
Role of the family therapist

Beels and Ferber,(34) early observers of possible roles for family 
therapists, divide them into ‘conductors’ and ‘reactors’; this differ-entiation remains useful since it transcends schools. Virginia Satir
(35) is a good illustration of the conductor given that she 
espoused the notion of family therapist as a teacher who shares her expertise in how to communicate well by setting goals and the direction of treatment. She guided the family to adopt a new form of language to resolve communication problems, which she saw as the root of their troubles. Additionally, the therapist instils confidence, promotes hope for change, and makes them feel comfortable. Conductor-type therapists are explicit authorities, who intervene actively.

The therapist as reactor resonates with, and responds to, what 
the family exhibits to her. Psychoanalytically oriented and ‘pure’ systems therapists are representative since they typically share observations about patterns of relating that emerge. We will illustrate this in our account of the Milan school.
(12)

1387
The Milan approach
With assessment complete, the therapist (sometimes a pair) meets 
the family for about an hour. With her preparatory knowledge, she develops a hypothesis about the nature of the family’s dysfunction. She has the opportunity on observing patterns in vivo  to conﬁ  rm 
her notions. Patterns usually emerge from the start, making the therapist’s job correspondingly easier. Apart from hypothesis-testing, another key task is to engage the family so they will be motivated to reattend. We could interpolate a dictum here: a pri-mary aim of the ﬁ  rst session is to facilitate a second session. A vital 
element in encouraging engagement is for the therapist to promote a sense of curiosity in family members so that they raise questions about themselves and the family as a group.
(36)
The chief strategy is circular questioning.(37) Its main purpose is

(36)
The chief strategy is circular questioning.(37) Its main purpose is 
to address the family’s issues indirectly; this avoids applying pressure on members and possibly inviting their resistance. For example, the therapist questions an adolescent about how his par-ents get on with each other, a mother about how her husband relates to the eldest son, a grandmother about which grandchild is closest to the parents, and so forth. This generates illuminating data about individual members and about the family as a group. In this phase, it helps to clarify the hypothesis and to engage par-ticipants. It also affords the therapist a greater facility to remain neutral. Because the system and not a patient is the target of change, the therapist is wary of showing any bias.
Various options are then available. If the therapist works as part 
of a team, her colleagues have busily observed the proceedings 
through a one-way screen. The family’s consent for this will of

through a one-way screen. The family’s consent for this will of 
course have been obtained. During a break, the team—observers and therapist(s)—pool impressions.
(38) This is always enlightening 
since team members note something that others have missed. A consensus evolves, conclusions are drawn and converted into ‘messages’ . The therapist returns to the family to convey them. The actual messages and their oracular quality comprise a potent intervention, but not necessarily more cogent than circular ques-tions made during the working session. We should mention here that the narrative school has brought with it a de-emphasis on the ‘message’ on the grounds that ‘truth’ is a shared construction.
One to three messages are usually given, with maximal clarity.

One to three messages are usually given, with maximal clarity. 
These have a range of purposes including promotion of inter-sessional ‘work’ . Homework may be assigned and another session planned (unless termination was set for this point). Meetings com-monly occur 3 to 4 weeks apart, and for good reason. During this 
time, the family, armed with new ideas, tackle them in their day-to-day lives. It is not critical how they go about it but that they do so. 
As Cecchin has posited,
(36) the family’s interest in their functioning 
should have been so aroused that they will be motivated to continue looking at themselves between sessions.
The varied nature of the message makes them classiﬁ  able.
(39)
Messages are supportive, hypothesis-related, or prescriptive. First, 
the message has a reassuring and encouraging quality and is not related to the hypothesis. A complimentary message  might be that

the message has a reassuring and encouraging quality and is not related to the hypothesis. A complimentary message  might be that 
‘The team were impressed by how open you all were in the session’ , and a reassuring message  that ‘This is tantamount to a new start for 
the family and uncertainties are likely’ .
Hypothesis-related messages  refer to the hypothesis worked out by 
the team, and may assume diverse forms. It may be stated directly; for example, ‘Susan has assumed the role of therapist for her parents and sister to save the family from breaking up’ . There may be 
reference to change such as, ‘The team sees John taking responsibility; John and his father’s improved relationship has enabled this to occur’ . The family may be offered choices related to the hypothesis; for instance, ‘The family could risk openness or remain self-preoccupied’ . Paradoxical messages  are a means to communicate a

hypothesis which invites the family to revisit a feature of their func-tioning so that the family’s difﬁ  culties are positively promoted and 
explicitly encouraged; for example, ‘The team sense that your prob-lem is working for the good of your marriage; sticking with your illness can save the marriage’ . More creatively, the paradox may be split, in that the family are told about a divergence of opinion in the team
(40); for instance, some members believe it is too risky for them 
to communicate openly, others suggest the family can begin to do so. Through a prescriptive message  the family is given a task. This 
may or may not be related to the hypothesis. For example, the fam-ily is urged to meet on their own before the next session to explore what inhibits a member from relating closely to the others.
Whatever the form of message, the therapist de-emphasizes the

Whatever the form of message, the therapist de-emphasizes the 
pathological status of the patient and applies what the Milan school calls positive connotation . This brilliant innovation rests on the 
premise that all behaviour is purposeful, and that the purpose can be construed positively. An adolescent’s ‘open grieving’ is reframed as sparing the family the anguish of grief. This quality of message calls for creative thinking and ﬂ  ies in the face of the customary 
view of symptoms as evidence of psychopathology. Again, curiosity enters the picture as the family hears a positive communication 
concerning an issue they hitherto regarded as abnormal.
The process described continues in succeeding meetings, with

The process described continues in succeeding meetings, with 
attention also paid to family life between sessions. Duration of therapy depends on how entrenched the family dysfunction is rather than on the status of the patient’s problems. Thus, systemic change is aimed for, with the family invited to consider a substitute mode of functioning that is feasible and safe. In practice, the number of sessions ranges from 1 to 12. If progress has not been made by about the seventh session, it is likely that alternate ways of helping family and/or patient are needed.
Ending therapy

T ermination issues are less profound than in individual or group therapy. The reason is obvious. The family has come as a living unit and will continue as such. Even when the therapist is a pure con-ductor, the family’s intrinsic resources are highlighted so that they can be drawn on after the therapist’s departure. Determining the end-point is not usually problematic. There is a shared sense that the work has been accomplished.
A hypothesis (or set of hypotheses) has been introduced, tested, 
and conﬁ  rmed. The family system has been examined so that 
impediments are recognized and understood and better modes of functioning devised and implemented. The family is not required to leave functioning optimally. Instead, termination occurs when there is agreement that the family feels conﬁ  dent to try out newly 
discovered options.
As alluded to earlier, this may be determined alongside a judge-
ment that the identiﬁ  ed patient (or another family member)

ment that the identiﬁ  ed patient (or another family member) 
requires another form of therapy in their own right. An adolescent who has felt unable to separate and individuate is a good example. While family work has explored the system that hindered his 6.3.8 family therapy in the adult psychiatric setting

SECTION 6  treatment methods in psychiatry 1388
‘graduation’ , the sense prevails that he could beneﬁ  t further from 
individual or group therapy. In another example, the parents may conclude, with the therapist’s support that they have an agenda which is not pertinent to their children and is therefore best under-taken in couple therapy.
Problems encountered in therapy
Where assessment has been carried out diligently and motivation for change sustained, treatment proceeds smoothly. A crisis may still buffet the group but, rather than being derailed, the family regard it as a challenge with which to grapple.
Family treatment does not always succeed. Indeed, deterioration 
may occur, albeit in a small percentage of cases. What common dif-ﬁ culties are encountered? The non-engaging family is problematic

may occur, albeit in a small percentage of cases. What common dif-ﬁ culties are encountered? The non-engaging family is problematic 
in that while evidence points to the need for family intervention, members cannot participate in the task, usually because they resist letting go of ‘the devil they know’ . In another variation, engage-ment of some members may fail. This is particularly so in the case of fathers who, in the wake of their denial, tend to see the target of therapy as the identiﬁ  ed patient rather than the family as a group. 
This belief may apply to any member.
Missed appointments may punctuate therapy, often linked to 
turbulent experiences between sessions or apprehension about what a forthcoming session may engender. Like any psychotherapy,

turbulent experiences between sessions or apprehension about what a forthcoming session may engender. Like any psychotherapy, 
drop-out is possible. On occasion, this is appropriate in that the indication for family therapy was misconstrued. In other circum-stances, drop-out is tantamount to failure and may stem from such factors as therapist ineptitude, unearthing of family conﬂ  ict which 
they cannot tolerate, and inappropriate selection of a family based on faulty assessment.
Given that the family continues as a living group during treat-
ment, they are exposed to all manners of vicissitudes, and these may disrupt the therapeutic work. For example, an overdose by the patient, abrupt marital separation, or admission to a psychiatric hospital may take its toll and undermine treatment.
In discussing termination, we commented on outcome. Not all 
families will beneﬁ  t. The family’s dysfunction may be so intractable

families will beneﬁ  t. The family’s dysfunction may be so intractable 
that it proves impervious to change, hypotheses may be ‘off the mark’ , the family may lack sufﬁ  cient psychological-mindedness, 
members may retreat in the face of change because of insecurity, and so forth.
Occasionally, dependency becomes a problem as the family dis-
cards any vestige of autonomy and only feels secure in the authori-tative hands of the therapist. The latter may inadvertently foster such dependency by assuming undue authority, so precluding any sense of a growing partnership. The family’s inherent resources are then not permitted expression.
Finally, part of the family may harbour a secret that threatens the 
principle of open communication. The therapist may be inveigled 
into a subgroup, although knowing that secrets are not conducive

into a subgroup, although knowing that secrets are not conducive 
to the therapeutic process. For example, a wife calling the therapist to say she has been having an affair but cannot divulge this to her husband or children lest she hurt them imposes a burden on the therapist and the process (see Bloch et al .
(27) for an overview of 
conﬁ  dentiality in family therapy).
Sound clinical judgement is required in all these situations. Since 
no ready-made prescriptions are available, the therapist must be aware that difﬁ  culties may occur even in a highly motivated, 
well-selected family. The general principle, however, is to prevent their evolution if at all possible or to recognize them early and ‘nip 
them in the bud’ .
Research in family therapy
Selective reviews of the vast research literature in family therapy have been provided by Carr.

(41,42) Larner(43) has examined political 
and conceptual issues raised by family therapists’ attempts to con-form to the criteria of evidence-based practice while Stratton and his colleagues
(44) have looked at the impact of such research on 
clinicians. An argument for the continuing relevance of single-case studies has been mounted by Datillio
(45) and the possibilities of 
conducting qualitative research in a systems model by Burck.(46)
The long-standing debate between the role of ‘common basic 
factors’ versus ‘model-specific factors’ , which has bedevilled research in individual therapy, also pertains to family therapy. Simon
(47) has proposed a testable hypothesis, rich in its implica-

tions, that the most effective model is one whose concepts and val-ues most closely resemble the world view of the therapist. He offers this as a conceptual bridge between the two approaches to thera-peutic research, although he curiously says nothing about the fam-ily’s world view.
Modifying the psychoeducational model of family-based treat-
ment to incorporate clinically relevant socio-cultural factors has been proposed for the treatment of adolescents and young adults suffering from schizophrenia
(48) and depression.(49)
In appraising the contemporary state of family therapy research 
in adult clinical psychiatry, we may be cautiously optimistic. Immense strides have been made in developing theoretical concepts. As can be seen in the ﬁ  rst section of the chapter, we have a rich

in adult clinical psychiatry, we may be cautiously optimistic. Immense strides have been made in developing theoretical concepts. As can be seen in the ﬁ  rst section of the chapter, we have a rich 
array of therapeutic approaches.
(50) On the other hand, the growth 
occurred at a dizzy pace, with the inevitable consequence of overload. How can we make sense of so many offerings? Is integra-tion needed to forestall fragmentation? Have we reached the point to pause and reﬂ  ect? Are we in a position to evaluate the effective-
ness of diverse approaches, and for various types of clinical problems?
Observers of the research
(51, 52) have pointed to a complicating 
factor in contemplating future work, namely the therapist assem-bling a natural group, of varying composition, in which the princi-pal goal is to improve its functioning. We face the conundrum of what constitutes optimal outcome and how it is best measured. We can best illustrate this by citing Asen and his colleagues.
(53)

(53)
In their trial of family therapy they had agreed to apply multidi-mensional measures to assess outcome—at individual, dyadic, and family system levels. At follow-up they noticed changes at the ﬁ  rst 
two levels, but not in the family as a whole. The latter involved ratings of such aspects as communication, boundaries, adaptability, and competence. The researchers were candid in sharing their doubts about how to deal with the divergent ﬁ  ndings. Several inter-
pretations were offered: for example, no change was achieved in family functioning, the instrument of family functioning was non-reactive to treatment since it was a trait measure, and an inap-propriate model of therapy was applied in the ﬁ  rst place. The group 
concluded that the ‘assumptive worlds’ of therapists and research-ers were under scrutiny rather than the families themselves.
A group in Oxford
(54) encountered similar difﬁ  culties in their

(54) encountered similar difﬁ  culties in their 
study of consecutive families treated in an adult family therapy clinic. Whereas two-thirds of the identiﬁ  ed patients were judged 
improved at termination, only half the families were rated as

1389
functioning at a better level. Again, the investigators were left with 
questions of how to determine what had actually been achieved.
A methodologically simpler method is to focus only on the iden-
tiﬁ ed patient. The work of Hafner et al.(55) exempliﬁ  es this choice—
a case-controlled evaluation of family therapy in an inpatient set-
ting with subsequent hospital admission data as the chief outcome criterion. Satisfactory as this study is in design, the omission of a family-system outcome measure leaves us ignorant about the level of family functioning following the intervention.
With these tricky matters in mind, what does research need to 
sort out? The diffuse question of whether family therapy works is of little utility, and is reminiscent of the sterile debate that typiﬁ  ed 
individual psychotherapy outcome research for decades.
(56) While

(56) While 
subsequent meta-analyses demonstrated that psychological inter-ventions overall exerted useful effects across a range of conditions, the ﬁ  eld was still open to the criticism that efﬁ  cacy of a speciﬁ  c 
approach for a particular clinical state remained unanswered. Family therapy should not repeat the same mistake; instead of posing the futile question of whether family therapy is effective in adult psychiatry, we should ascertain whether a speciﬁ  c family 
therapeutic approach, whose character is well identified and meas urable, is useful for both the identiﬁ  ed patient, with a speciﬁ  c 
clinical presentation, and his family’s functioning, again well deﬁ ned.
We have good examples of such research. Many intervention 
studies of families with a schizophrenic member have carefully described the principles of treatment, its rationale, process 
aspects, and outcome measures in the patient and (in some cases)

aspects, and outcome measures in the patient and (in some cases) 
the family.
(57–60)
As mentioned earlier, multiple family group therapy (MFGT) is 
emerging as the preferred psychosocial intervention for adolescents and young adults with schizophrenia. A comparison with the ‘open dialogue’ model we mentioned earlier has not been conducted, and may not be feasible, since the latter is part of a comprehensive treat-ment paradigm.
(61) A Danish study(62) which combined MFGT 
with assertive community-based treatment of young people with schizophrenia reported improvement not only of psychotic features (both positive and negative), but also a decline in use of alcohol and illicit drugs. Given the major problem of co-morbidity, this is a welcome development.
MFGT has also been directed to helping the caregivers of patients

MFGT has also been directed to helping the caregivers of patients 
with schizophrenia. In a randomized controlled trial, Hazel et al.
(63)
found that those in the treatment programme for over a 2-year 
period experienced greater relief from distress compared to con-trols, but they were not able to determine the mechanism for this effect.
Work in the area of affective disorders and family therapy has 
been innovative, with MFGT, again, gaining popularity.
(64) As in 
schizophrenia, the family treatment aims to reduce members’ hostility and criticism expressed toward the depressed patient.
An excellently designed and executed study on anorexia and 
bulimia nervosa illustrates how outcome research can contribute to the clinical sphere.
(65) In a well-controlled study, patients were ran-

domized to either family therapy or ‘routine individual supportive therapy’ , following their discharge from a weight-restoration programme. The family intervention focused on providing the members with information about the eating disorder and the effects of starvation. Parental anxiety was acknowledged and efforts made to help them take control of their daughter’s diet. In parallel with improved physical status, therapy turned progressively to 
typical adolescent issues of autonomy and how these might be achieved. Overall, a structural approach was applied, with systemic and strategic methods added as necessary. Applying these princi-ples to groups of families with adolescents with anorexia nervosa appears to be useful.
(66)
While the above studies concerning particular diagnoses, and

(66)
While the above studies concerning particular diagnoses, and 
involving an identiﬁ  ed patient, is necessary for progress,(67) this 
does not preclude outcome studies where the family system is the main target of change. We illustrate this with a particular form of family grief therapy.
(68) The model was derived from earlier empir-
ical research on the outcome of family grieving in an oncology setting. A 13-month follow-up yielded ﬁ  ve family clusters, two of 
which were distinctly dysfunctional, two functional, and an inter-mediate group vulnerable to maladaptive grieving. Three dimen-sions of family relational functioning were critical: cohesiveness, conﬂ  ict, and expressiveness. The researchers then developed a 
treatment model highlighting the goals of promoting cohesiveness, expressiveness, and optimal management of conﬂ  ict. A screening

treatment model highlighting the goals of promoting cohesiveness, expressiveness, and optimal management of conﬂ  ict. A screening 
instrument was found which could readily identify dysfunctional families. A randomized controlled trial was then carried out which showed certain family types benefiting but others remaining unchanged, and a small group even being made worse.
(69)
This necessarily schematic account of research on family therapy 
in adult psychiatry points to action needed in future. We can best summarize what investigators should strive for as: ‘Speciﬁ  city is of 
the essence’ .
Training
From charismatic ﬁ  gures devising innovative methods of family 
therapy, the ﬁ  eld has developed into a worldwide enterprise, with 
dozens of books, scores of training courses, several journals, and a busy programme of national and international conferences and workshops on offer.
(70) Formal training may be given as follows(71):

1 University-based programmes that regard family therapy as a 
distinct professional pursuit, with a corresponding corpus of knowledge, and offer degree courses at various academic levels.
2 Free-standing institutes that also see family therapy as a distinct 
discipline and provide training, generally part-time and of briefer duration than university-based programmes.
3 Within university-afﬁ  liated hospitals and clinics that arrange 
professional training in psychiatry, psychiatric nursing, psychol-ogy, social work, and occupational therapy. Although there is a tremendous diversity in the above programmes, most include:
◆ Supervision of clinical work with the experienced practitioner

◆ Supervision of clinical work with the experienced practitioner 
(and perhaps other students) observing the trainee and family from behind a one-way screen. Some clinicians however consider the one-way screen as dehumanizing. They advocate instead a model of co-therapy between trainee and supervisor, often with other students sitting in the same room as the family.
◆ Video recording the trainee’s work, which she then reviews 
with the supervisor and fellow students, is widely used. Tapes conducted by eminent therapists are also popular.
Whether training requires familiarity with concepts and techniques
of diverse schools or whether it is preferable to develop expertise in only one school remains an open question. The free-standing institutes tend to be run by practitioners of a particular school so 6.3.8 family therapy in the adult psychiatric setting

SECTION 6  treatment methods in psychiatry 1390
that, after a mostly cursory overview of the ﬁ  eld, training con-
centrates on a speciﬁ  c model. Wendel and his colleagues(72) have 
proposed a model of training for multidisciplinary mental health settings which places most emphasis on integrating empirically derived knowledge; ﬂ  exibility is a crucial feature for facilitating its 
optimal application.
Family therapy has the potential to play a major role in the adult psychiatric setting. As we have commented above, research reveals several promising developments. Clinicians should seriously con-sider applying this mode of treatment; they will be much rewarded in doing so.
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6.3.9 Therapeutic communities
Two of the best-known pioneers of therapeutic communities, T om 
Main and Maxwell Jones, deﬁ  ned them as follows:
An attempt to use a hospital not as an organization run by doctors 
in the interests of their own greater technical efﬁ  ciency, but as a 
community with the immediate aim of full participation of all its members in its daily life and the eventual aim of the resocialization of the neurotic individual for life in ordinary society.
(1)
What distinguishes a therapeutic community from other comparable treatment centres is the way in which the institution’s total resources, staff, patients, and their relatives, are self-consciously pooled in furthering treatment. That implies, above all, a change in the usual status of patients.
(2)

(2)
T oday therapeutic communities can be deﬁ  ned by a number of 
common features, but a word of warning. For reasons of historical coincidence, the term is used in the ﬁ  elds of mental health and 
addictions to refer to two somewhat different treatment models. In the addiction ﬁ  eld they are also known as hierarchical, drug-free or 
concept-based therapeutic communities, or simply addiction therapeutic communities,
(3) in contrast to the more democratized 
programmes in mental health. The two models have similar goals but their methods differ, although there are signs of increasing rapprochement between them. This chapter deals mainly with therapeutic communities in mental health, but reference will also be made to addiction therapeutic communities and those in long-term care settings. It is worth noting that those admitted to a thera-peutic community for treatment are usually referred to as residents, clients, or members, rather than as patients.6.3.9 therapeutic communities

SECTION 6  treatment methods in psychiatry 1392
Deﬁ ning beliefs
Certain beliefs about human relationships and the nature of therapy 
are central to therapeutic communities.
1 Staff are not completely ‘well’ and residents are not completely 
‘sick’ . There is a basic equality as human beings between staff and residents, who share many of the same psychological processes and experiences.
2 Whatever the symptoms or behaviour problems, the individual’s 
difﬁ culties are primarily in his or her relationships with other 
people.
3 Therapy is essentially a learning process, both in the sense of learn-
ing new skills—how to relate to others or deal more appropriately with distress—and learning to understand oneself and others.
Deﬁ ning principles
A study of one of the best-known therapeutic communities, 
Henderson Hospital,(4) identiﬁ  ed four principles or ‘themes’ that 
have come to be widely associated with therapeutic community treatment.
Four principles of therapeutic community treatment

◆ Democratization  Every member of the community should 
share equally in the exercise of power in decision-making about community affairs.
◆ Permissiveness  All members should tolerate from one another 
a wide degree of behaviour that might be distressing or seem deviant by ordinary standards.
◆ Communalism  There should be tight-knit intimate sets of 
relationships, with sharing of amenities (dining room etc.), use of ﬁ rst names, and free communication.
◆ Reality confrontation  Residents should be continuously 
presented with interpretations of their behaviour as it is seen by others in order to counteract their tendency to distort, deny, or withdraw from their difﬁ  culties in getting on with others.
Deﬁ ning aspects of current practice

The generalizability of these principles to newer therapeutic 
communities is now being questioned and others are developing theoretical frameworks for different therapeutic communities.
(5)
In 2002, a quality network including most British therapeutic com-munities started, the ‘Community of Communities’ , with the explicit aim of deﬁ  ning good practice and improving it. In 2006 the 
ﬁ rst version of ‘Core Standards’ was published.
(6) This comprised 
16 standards which were derived from consensus and consultation exercises to determine what practitioners and service users thought reﬂ ected the underlying values of therapeutic communities.
Box 6.3.9.1 illustrates a sample of eight of the standards. Note 
that ‘all community members’ should be taken to include both res-ident or client members, and staff.
Evolution of different types of therapeutic community

Communities providing sanctuary for mentally ill people have been known as far back as the fourteenth century at Geel in Belgium. In 1796 the Retreat was opened by the Quakers in Y ork, England, 
where personal relationships and social expectations in a family-like atmosphere enabled previously dangerous and unpredictable 
individuals to control and modify their behaviour.
(7) This model, 
known as ‘moral treatment’ , strongly inﬂ  uenced the creation of 
asylums in Britain and the United States in the ﬁ  rst half of the

asylums in Britain and the United States in the ﬁ  rst half of the 
nineteenth century. In the early twentieth century, pioneers in ther-apeutic education, inspired by a Christian belief in the therapeutic power of love and by Freud’s new method of psychoanalysis (see Chapter 3.1), created residential schools for maladjusted children that demonstrated most of the practices and attitudes outlined above.
(8) The modern equivalent of communities such as Geel 
can be found in the intentional communities run by third sector (voluntary) organizations such as l’Arche and the Camphill communities for people with learning disabilities. (The term ‘intentional community’ avoids language that implies clinical responsibility or a focus on therapy or change, and has been deﬁ  ned

as ‘a relatively small group of people who have created a whole way of life for the attainment of a certain set of goals’ .) A number of therapeutic communities for children and young people now exist as voluntary organizations in the educational sector, as progressive schools, and as long-term treatment units for very disturbed children.
The history of mental health therapeutic communities for adults 
began during the Second World War, when the psychoanalyst 
Wilfred Bion was put in charge of the training wing at Northﬁ  eld 
Military Hospital in Birmingham, England. His brief attempt in 1943 to establish a therapeutic community failed, but was soon followed by others who were more successful: T om Main, S. H. Foulkes, and Harold Bridger at Northﬁ  eld, and Maxwell Jones at 
Mill Hill Hospital, London. In dealing with psychiatric casualties among soldiers they developed a radical new approach, which was ﬁ rst described in a series of papers in 1946. One of these coined the

term ‘therapeutic community’ .
(1) Main and Jones continued to 
develop different versions of this new method after the war, Main as director of the Cassel Hospital and Jones at Belmont Hospital Industrial Neurosis Unit, which was renamed the Henderson 
Box 6.3.9.1 Core standards for therapeutic communities
1 The whole community meets regularly2 All community members work alongside each other on day-
to-day tasks
3 All community members share meals together
4 All community members can discuss any aspects of life within 
the community
5 All community members create an emotionally safe environ-
ment for the work of the community
6 All community members participate in the process of a new 
client member joining the community
7 There is an understanding and tolerance of disturbed behav-
iour and emotional expression
8 Positive risk taking is seen as an essential part of the process 
of change

1393
Hospital in 1958. The Cassel Hospital continues as an inpatient 
psychotherapy hospital, and Henderson Hospital replicated itself in 2000 to serve national needs for ‘severe personality disorder’ provision by founding Main House in Birmingham and Webb House in Crewe.
The creation of the National Health Service in 1948 provided the 
stimulus to address the major problems of institutionalization revealed in a number of studies of large mental hospitals in the United Kingdom and United States.
(9,10)  In the 1950s and 1960s 
social psychiatry was in the ascendancy and a number of these hospitals developed what Clark called the ‘therapeutic community approach’’ .
(11) In the 1970s and 1980s concepts of collective respon-

sibility fell from favour and individualism prevailed, with a decline in the fortunes of therapeutic communities. The 1990s and 2000s have seen a revival of interest in therapeutic communities within more speciﬁ  c mental health contexts, including prisons, personality 
disorder services, and for the management of people with enduring mental illness in the community. The problem of degraded and poorly functioning inpatient units is now being addressed by atten-tion to establishing and maintaining ‘therapeutic environments’ in acute settings, in a direct parallel to the ‘therapeutic community approach’ 40 years earlier.
(12,13)
Alongside these developments two other types of therapeutic

(12,13)
Alongside these developments two other types of therapeutic 
community have emerged. In 1958 a self-help organization in the United States called Synanon became the prototype for concept-based therapeutic communities for ex-addicts. Phoenix House and Daytop were two major programmes that grew from this, and today therapeutic communities modelled on them can be found in more than 50 countries worldwide.
(3) A development that grew out of 
the antipsychiatry movement in the 1960s is known at Soteria. These are small low-stress family-like environments where psycho sis 
is responded to with intensive therapeutic support rather than medication. These communities are mainly found in Europe.
(14)
Scientiﬁ  c background
Therapeutic communities have drawn on the concepts of psycho-
analysis, group analysis (see Chapter 6.3.6), humanistic and integrative psychotherapies, and on sociological studies of mental hospitals which identiﬁ  ed phenomena such as the total institution
(10)

(10)
and patterns of behaviour associated with psychiatric treatment in 
institutions.(15) They are also underpinned by studies of the impact 
of unconscious processes in organizations,(16,17)  and by anthropo-
logical studies such as that of Rapoport(4) which found a typical 
pattern of oscillation in the therapeutic community.
A developmental model based on the ‘required emotional expe-
riences’ of attachment, containment, communication, inclusion, and agency has been proposed by Haigh.
(18) This identiﬁ  es ways 
in which a range of psychological theories and approaches are relevant to therapeutic community practice, and illustrates how they are replicated in the structures and culture of a therapeutic community. It also proposes that disturbance of ‘primary emotional development’ (which all humans undergo early in life) can to some extent be made good by a satisfactory experience of ‘secondary emotional development’ in a therapeutic community.
Technique—how change is brought about

Since the therapeutic community is the treatment, managing treat-
ment involves attention to two parallel processes: the progress of each resident through the community, and the effective function-
ing of the therapeutic community as a whole. Responsibility for managing these two processes ultimately belongs to the staff, though it is shared with the residents when the community is func-tioning well.
Most if not all the treatment in a therapeutic community takes 
place in groups and in the everyday life of the community, although some also use individual psychotherapy. The essence of the therapeutic community technique has been encapsulated in two phrases.
1 A living–learning  situation: this refers to the fact that everything 
that happens between members of a therapeutic community in the course of living together, and in particular when a crisis occurs, is used as a learning opportunity.
(19)

(19)
2Culture of enquiry : this refers to the creation not just of certain 
structures but of a basic culture among the staff of ‘honest enquiry into difﬁ  culty’ . There is a conscious effort to identify and 
challenge dogmatic assertions or accepted wisdoms.
(20)
The basic mechanism of change is not difﬁ  cult to explain. The 
therapeutic community provides a wide range of lifelike situations in which the difﬁ  culties a member has experienced in their rela-
tionships with others outside are re-experienced, with regular opportunities in small group and community meetings to examine and learn from these difﬁ  culties. If the therapeutic community is

tionships with others outside are re-experienced, with regular opportunities in small group and community meetings to examine and learn from these difﬁ  culties. If the therapeutic community is 
to work as a therapeutic method, all its constituent parts described in this chapter must be in good-working order. This requires a pro-cess by which new members adopt the values of the community, emphasizing openness, responsibility, and active participation, and in turn pass these on when the next new members arrive. T o operate this mechanism requires both staff and residents to fulﬁ  l 
a number of roles (Box 6.3.9.2).
Staff training
The need for specialized training for leading or working as a staff member in a therapeutic community has been a matter of some debate.
(21) There is an argument that the emphasis on egalitarianism

and democratization means that this form of treatment is best delivered by people without special training who can just ‘be themselves’ . Unqualiﬁ  ed social therapists often form a key part of 
the staff complement. However, the other argument is now increas-ingly accepted, that while being oneself is an important part of the staff role (see above), therapeutic community work requires a high level of skill and knowledge in a number of areas, together with a well-developed capacity for open honest discussion and reﬂ ection.
Training courses exist in the United Kingdom, Finland, Norway, 
the Netherlands, and Greece, but there is no set standard or curriculum. Some relevant theoretical training is obtainable as part of group therapy and systemic therapy courses, and the case has

the Netherlands, and Greece, but there is no set standard or curriculum. Some relevant theoretical training is obtainable as part of group therapy and systemic therapy courses, and the case has 
also been made for a placement in a therapeutic community to be 
part of professional training in psychiatry and psychotherapy. The beneﬁ  ts include learning at ﬁ  rst hand about the treatment of 
personality disorders, experience of group-based treatment, and 
working as a member of a multi-disciplinary team, thus gaining 
first-hand experience of institutional dynamics and the way individuals react to their wider social networks. One of the most popular short courses in the United Kingdom and the Netherlands 6.3.9 therapeutic communities

SECTION 6  treatment methods in psychiatry 1394
is a brief residential simulated therapeutic community.(22) Here, 
20 to 30 health professionals live together for a few days in the roles of residents with a ‘staff’ group working with them. This provides a valuable opportunity to experience at ﬁ  rst hand the workings and 
impact of this form of treatment.
Universal indications for therapeutic community treatment are difﬁ cult to give. Modiﬁ  ed therapeutic communities have been 
developed for people with different types and levels of psychiatric disorder, and even the same therapeutic community may ﬂ  uctuate in 
its capacity to absorb difﬁ  cult members. An individual’s suitability 
will need to be judged in relation to a particular therapeutic com-munity at a particular time. Having made this caveat, the general indications and contraindications will usually apply (Box 6.3.9.3).
Pathways and process: phases in the 
therapeutic journey

There are usually four distinct but overlapping phases in a member’s 
journey to and through a therapeutic community:Engagement phase : Referral, preparation, and selection procedures 
are an integral part of therapeutic community practice, involving both the prospective member and existing residents as active participants in the process, which start with referral or self-referral. Many prospective members of therapeutic communities are 
wary or fearful of the forthcoming therapy, and need support 
and encouragement to persist. This is often effectively delivered by current or ex-members, arranged in partnership with voluntary agencies, or with internet support groups. During this time, any regular support from mental health teams or other agencies should continue.
Assessment and preparation phase : When a decision to proceed

Assessment and preparation phase : When a decision to proceed 
towards formal treatment has been made, several arrangements may need to be made. These include formal assessment processes, practical planning, and agreeing a treatment contract. This work is frequently arranged through the use of an ‘assessment and prepara-tion group’ , which is also designed to be a time-limited foretaste of 
what the treatment phase entails. The assessment process can be 
undertaken in this group itself, in smaller groups, or with individual 
appointments. The practical planning involves matters such as arranging childcare, securing stable accommodation, and agreeing plans for medication and risk management. It also includes an Box 6.3.9.2 Staff and client/resident roles in a therapeutic community
Role Role activity of client/resident members Role activity of staff members

Participation and involvement in the daily To explain how the community works to To spend informal time with client/residents (th ose
life of the community(‘Living–learning’) those referred, to visitors, and new members who appear aloof may be challenged about th is)
To take responsibility for various tasks which To work alongside clients/residents in
contribute to the running of the community day-to-day tasks
To contribute to various ‘extras’ such as To monitor other staff members’ emotional
being involved in teaching and research involvement and consider in supervision
To notice and include those who isolate themselves
Contributing to and managing therapeutic To use identiﬁ  cation to challenge or support peers To use therapeutic interventions in groups of various
processes (‘Culture of enquiry’) modalities (e.g. group analytic, psychodrama, art 
therapy, CBT)

To be open to the challenge and support To encourage client/resident members to take a
of one’s peers therapeutic role, in some cases delegating
responsibility for out-of- hours support to them
To support those in crisis, often including
out-of-hours
To maintain community structures such as
rules and timekeeping
Responsibility for decision-making and To make decisions about day-to-day and To decide the level of decision-making which would be
‘Democratization’ domestic matters, including rotas and elections optimal for the therapeutic beneﬁ  t of the client group,
according to their capabilities and needs
To participate in decisions about therapeutic To monitor the functioning of the therapeutic
matters (e.g. deciding consequences of 
breaking rules)environment and titrate the level of staff input and 
leadership required

To be involved in planning local events and service To ensure good communication with managers, 
developments (e.g. open days, starting new groups) commissioners, referrers, clinical colleagues, and other 
relevant organizations
Senior and ex-members can offer invaluable
support in maintaining effective externalrelations (e.g. with organizational executives)

1395
explicit treatment contract, which may be a verbal agreement about 
understanding the community rules, or a formal written and signed agreement.
Treatment phase : This usually begins with a formal ‘case confer-
ence’ or ‘selection panel’ including current community members with a decision made by voting. Subsequent therapy programmes vary considerably: from 1 day per week to whole-time residential; from predominantly sociotherapy to a range of psychoanalytic, cognitive behavioural, humanistic and interpersonal and systemic groups; from a few weeks duration to several years, either time-limited or open-ended; and from group size of less than 6 to more than 50. Some communities include individual therapy, but others consider this inimical to the group dynamic process. A modal or typical programme would be for between 3 and 5 days per week, 
with all interventions in groups comprising a mixture of commu-

nity meetings, small therapy groups, shared lunch, and informal time together. A typical community would have between 12 and 24 members divided into three small groups, who would stay for 12 to 
18 months. Suitable arrangements would be in place for crisis 
meetings to be called at short notice, as would a system for mem-
bers to support each other out-of-hours.
During the ﬁ  rst few weeks of treatment the new member will be 
feeling his or her way, forming attachments to one or two others, but still wary of the groups. After the ﬁ  rst month or two he or she 
will begin participating more actively in the groups, taking part in the full life of the community with certain role responsibilities, helping and supporting other members. This will probably include experience of situations similar to those triggering referral, such as 
having to deal with authority, fear of failure, feeling rejected or

having to deal with authority, fear of failure, feeling rejected or 
abandoned, situations evoking rivalry and competition, or many others. As before, these may trigger destructive or violent impulses towards the self or another person, or the experience of other symptoms of distress. Through the group meetings the mem-ber is confronted with the effects of their behaviour on fellow members and the meaning of the behaviour or symptoms is 
explored, making full use of the insights and understanding of fel-
low members. Through this repeated process the member gradu-ally comes to experience himself and others differently. As one member wrote: Bit by bit, almost grudgingly, the fact dawned on me that I wasn’t surrounded by forty sticks of furniture but by Jim, Gary, 
Jane . . . 
(23)
Re-entry phase : Until recently, many therapeutic communities had

Jane . . . 
(23)
Re-entry phase : Until recently, many therapeutic communities had 
a ‘cliff-edge’ ending, where one day members are able to have the community’s full emotional and practical support, and the next are not allowed to contact any other members. Although this has some theoretical justiﬁ  cation in terms of ‘coming to term with endings’ , 
and has strong advocates amongst ex-members of therapeutic com-munities, it is now generally considered better practice to support members over the leaving process, and then into re-establishing mainstream social networks. This can be done with a speciﬁ  c ‘leavers 
group’ , that members join while in the full treatment phase and con-tinue afterwards, for either a ﬁ  xed or indeﬁ  nite period. These groups 
normally include a practical focus, and are social and supportive 
rather than exploratory and therapeutic. For those who are ready and able, they can have objectives of securing employment or educa-

tion for members. In the case of prison-based therapeutic communi-
ties for ex-addicts the provision of drug-free housing and vocational 
training have been found to improve success rates.
(24)
As well as planned endings there are various other types of 
ending. Some members may leave prematurely, unable to cope with 
therapy; some may be ‘voted out’ by the community for a serious or 
repeated transgression of community rules. Such endings do not necessarily indicate a treatment failure, although the longer mem-bers remain the more likely they are to beneﬁ  t.
Research evidence
The effectiveness of therapeutic communities has been investigated 
in relation to different clinical problems, which are discussed 
separately.

Until recently there has been little systematic evidence of the efﬁ  -
cacy of therapeutic communities for treating personality disorders, and disagreement over whether those who did beneﬁ  t were really 
suffering from psychopathic or personality disorder. While efﬁ  cacy 
in this area is still questioned (see Chapter 4.12.7), the picture has recently become clearer with the publication of the ﬁ  rst systematic Box 6.3.9.3 Indications and contraindications for therapeutic community treatment
Indications Indications for specialized TC Contraindications
Diagnosis of:
◆ Personality disorder First episode psychosis Physically dependent addictions
◆ Self-harm Serious and enduring mental illness Current mania
◆  Adjustment disorders Less than 18 years old Depression with severe retardation

◆  Recurrent depressive disorders Learning disabilities Dementia
◆ Bipolar disorder Perpetrators of sexual abuse Dangerously low weight
◆ Intractable anxiety disorders Antisocial PD with history of intimidation and deception
◆ Eating disorder No capacity for social involvement
◆ Addictions Inability to see problems in terms of relationships
Unwillingness to engage in informal, intimate, and open style of relating
with professionals
Age:
No age limits: young children to elderly 
members can show beneﬁ  tBelief that only experts can help6.3.9 therapeutic communities

SECTION 6  treatment methods in psychiatry 1396
review of therapeutic community treatment for people with 
personality disorders.(25) The authors carried out a full search of 
therapeutic community publications and grey literature, collecting over 8000 references from 38 countries. These were reduced to 29 research studies that met the criteria of randomized controlled trial design (eight studies) or comparative or controlled studies that reported raw data and used conservative outcome criteria (e.g. reconviction rates rather than psychological improvement). A meta-analysis found that 19 studies showed a positive effect within the 95 per cent level of conﬁ  dence while the remaining 
10 straddled the neutral score. The overall summary log odds ratio was−0.567, with a 95 per cent conﬁ  dence interval, −0.524 to −0.614.

10 straddled the neutral score. The overall summary log odds ratio was−0.567, with a 95 per cent conﬁ  dence interval, −0.524 to −0.614. 
The authors concluded that there is strong evidence for the effec-tiveness of therapeutic communities. A more recent systematic review assessed evidence for interventions for people with PD in general and for dangerous and severe personality disordered offenders and made clear recommendations about the most promising treatment interventions for PD in use or currently in development. The reviewers covered therapeutic community programmes; cognitive, behavioural, cognitive behavioural, and psychodynamic psychotherapies; pharmacological and physical treatments. They concluded that ‘the TC model currently has the most promising evidence base in this poor ﬁ  eld’ .
(26)
Offending behaviour
Therapeutic communities have been established in prisons to deal

(26)
Therapeutic communities have been established in prisons to deal 
with disruptive, violent inmates, and also with the underlying problems of antisocial personality disorder. Results at Barlinnie Special Unit in Scotland demonstrated substantial reductions in violent incidents within prison. Reconviction studies carried out at Grendon, a prison run entirely on therapeutic community lines, found that prisoners had lower rates of reconviction, fewer custo-dial sentences, and fewer reconvictions for violent offences than prisoners on the Grendon waiting list who never went there. Those who stayed at Grendon longer than 18 months showed the greatest reductions in reconviction rates. Re-offending rates have also been found to be lower in the former Federal Republic of Germany for prisoners in Social Therapeutic Institutions than those receiving standard prison sentences.
(27) In 2004, the ‘Democratic Therapeutic

(27) In 2004, the ‘Democratic Therapeutic 
Community Core Model’ was accredited as a treatment programme for use in prisons in England and Wales. Such programmes must show evidence of their capacity to impact on dynamic risk factors known to be associated with re-offending. Risk factors that thera-peutic communities have been found to have a positive inﬂ  uence 
on include negative attitudes towards authority, identiﬁ  cation with 
antisocial role models, and acceptance of responsibility for offend-ing behaviour.
Drug dependence
Therapeutic communities for drug dependence use the hierarchical or concept-based model. These form one part of the range of treatments for drug abuse, which includes other residential models such as Christian communities and the Minnesota model, as well as methadone maintenance programmes and psychotherapy. Therapeutic communities for drug dependence, often modiﬁ  ed to

suit different local cultures, can now be found in many European and international countries as well as in the United States where they originated. Although the model began, and continues, as a residential peer-support programme in the community, it has 
adapted well to secure environments, and concept-based therapeu-tic communities for drug dependence have been established in American prisons since the mid-1980s, accompanied by a growing number of aftercare programmes providing employment and drug-free accommodation. Several national studies have evaluated the outcome of these programmes. Randomized controlled trials show that no-treatment groups have a higher level of recidivism than those who complete treatment in a prison therapeutic com-munity, and that recidivism is further reduced by participation in a community aftercare therapeutic community.
(24) Since 1995

(24) Since 1995 
a number of these therapeutic communities have also been estab-lished in English prisons. The general conclusion, for both secure and non-secure therapeutic communities, is that residents who stay in programmes for longer periods have lower rates of drug use and criminal behaviour and higher rates of employment than those who stay for shorter times. However, there are no direct compari-sons between therapeutic communities and other treatment models, and it is likely that therapeutic communities are successful for those who are well motivated. Although this may be only a rela-tively small proportion of all drug abusers, studies, and admission policies, suggest those who enter these high intervention therapeu-tic communities tend to be severely addicted and damaged, often dually diagnosed with personality disorder, and less likely to 
respond to low intervention treatments.
(28)
A small number of therapeutic communities have been developed

(28)
A small number of therapeutic communities have been developed 
in the United Kingdom, United States, Switzerland, and Germany on the principle that ﬁ  rst episodes of psychosis can be effectively 
treated in low-stress family-like settings providing round the clock personal support, with no or minimal use of neuroleptics. This has become known as the Soteria model. Two Soteria houses, in California and Berne, have been subjected to randomized or matched control trials comparing them with usual hospital treat-ment. One study found that completing subjects with schizophre-nia exhibited a large effect size beneﬁ  t with Soteria treatment, 
especially in the areas of psychopathology, work, and social func-tioning. Length of stay in Soteria Berne was initially longer but this was subsequently reduced to less than the admission ward. In both studies the 2-year outcomes were at least as good in the

Soteria group and less antipsychotics were prescribed for the 
Soteria group.
(14) A 20-year study of an acute psychiatric ward 
in Finland found that people with acute psychotic episodes and borderline conditions seemed to beneﬁ  t from the therapeutic 
community model with a high level of support, negotiation, order, and organization.
Severe and enduring mental illness
The therapeutic community approach(11) has been widely used in 
large mental hospitals to counter the effects of institutionalization 
and to mobilize the residual capacity of those suffering from chronic 
mental illness for social relationships, purposeful employment, and personal responsibility. The method was as much about improving the sense of purpose and morale of the staff and the general quality of life in the institutions as it was about clinical improvement, and its success was demonstrated in the way some large old mental hospitals were turned into centres of excellence.

1397
With the re-provision of services for people with enduring mental 
illness in the community, therapeutic community principles have been found to be an effective way of structuring staffed hostels and homes. In one version of this, the ‘ward in a house’ , the model is close to the original practice of the Y ork Retreat, an antecedent of therapeutic communities (see above).
(29) The challenges pre-
sented by the severely mentally ill chemical user have also been addressed using a modiﬁ  ed therapeutic community with some 
evidence of success. Three main modiﬁ  cations required to the TC 
structure were increased ﬂ  exibility, decreased intensity, and greater 
individualization.
(30)
Children and adolescents
Therapeutic communities for children and adolescents were ﬁ  rst 
developed in the ﬁ  eld of therapeutic education almost a century

(30)
developed in the ﬁ  eld of therapeutic education almost a century 
ago, and now exist for a variety of needs: learning disability, delin-quency, and emotional disturbance. Little systematic evaluation has been carried out. A survey of 186 children in nine therapeutic communities for emotionally disturbed children found evidence of increased stability and hopeful outcomes for those who stayed. A 20-year follow-up of 28 children in one community reported evidence of long-term improvement.
(31)
Wright and Richardson, reviewing the current state of research 
for therapeutic communities for children and young people, conclude that, ‘when rigorous quality controls are introduced there are as yet too few studies to draw any aggregated conclusions. Perhaps the clearest qualiﬁ  ed statement would be that there is low-

level evidence that some residential therapeutic placements produce changes in the mental and social functioning of some young people who have been unable to cope with family life’ .
(32)
Learning disabilities
Long-term residential communities for adults with learning disabilities exist in the charitable sector in many countries around the world. These are value based rather than evidence based. There is some evidence that many families express a strong preference for village-style communities such as the Camphill for their mentally handicapped relatives.
(33)
Campling, P . and Haigh, R. (eds.) (1999). Therapeutic communities: past, 
present and future . Jessica Kingsley, London.
Campling, P ., Davies, S., and Farquharson, G. (2004). From toxic institutions 
to therapeutic environments . Gaskell, London.
Community of Communities. (2006). Service standards for therapeutic 
communities . Royal College of Psychiatrists, London.

Kennard, D. (1998). An introduction to therapeutic communities  (2nd edn). 
Jessica Kingsley, London. www.therapeuticcommunities.org––website 
of the Association of Therapeutic Communities.
1. Main, T. (1946). The hospital as a therapeutic institution. Bulletin 
of the Menninger Clinic ,10, 66–70.
2. Jones, M. (1968). Social psychiatry in practice , pp. 85–6, Penguin, 
3. Rawlings, B. and Y ates, R. (2001). Therapeutic communities for the 
treatment of drug users . Jessica Kingsley, London.
4. Rapoport, R.N. (1960). Community as doctor . Tavistock, London. 5. Campling, P . and Haigh, R. (eds.) (1999). Therapeutic communities: 
past, present and future . Jessica Kingsley, London.
 6. Community of Communities. (2006). Service standards for therapeutic

 6. Community of Communities. (2006). Service standards for therapeutic 
 7. Tuke, S. (1813). Description of the retreat . Reprinted by Process Press, 
London, 1996.
 8. Bridgeland, M. (1971). Pioneer work with maladjusted children .
Staples Press, London.
 9. Barton, R. (1959). Institutional neurosis . John Wright, Bristol.
10. Goffman, I. (1961). Asylums . Doubleday, New Y ork; Penguin, 
Harmondsworth, 1968.
11. Clark, D.H. (1965). The therapeutic community—concept, practice 
and future. The British Journal of Psychiatry ,131, 553–64.
12. Campling, P ., Davies, S., and Farquharson, G. (2004). From toxic 
institutions to therapeutic environments . Gaskell, London.
13. Hardcastle, M., Kennard, D., Grandison, S., et al.  (2007). Experiences 
of mental health in-patient care: narratives from service users, carers and professionals . Routledge, London.

14. Ciompi, L. and Hoffman, H. (2004). Soteria Berne: an innovative 
milieu therapeutic approach to acute schizophrenia based on the concept of affect-logic. World Psychiatry ,3, 140–6.
15. Stanton, A. and Schwartz, H. (1954). The mental hospital . Basic Books, 
New Y ork.
16. Menzies, I. (1960). A case-study in the functioning of social systems as 
a defence against anxiety. Human Relations ,13, 95–121.
17. Main, T. (1957). The ailment. British Journal of Medical Psychology ,
30, 129–45.
18. Haigh, R. (1999). The quintessence of a therapeutic environment. 
In Therapeutic communities: past, present and future  (eds. P . Campling 
and R. Haigh), Chap. 20. Jessica Kingsley, London.
19. Jones, M. (1968). Social psychiatry in practice , pp. 105–12. Penguin, 

20. Main, T. (1983). The concept of the therapeutic community: variations 
and vicissitudes. In The evolution of group analysis  (ed. M. Pines), 
pp. 197–217. Routledge and Kegan Paul, London.
21. Roberts, J. (1998). Questions of training. In An introduction to 
therapeutic communities  (ed. D. Kennard). Jessica Kingsley, London.
22. Rawlings, B. (2005). The temporary therapeutic community—a 
qualitative evaluation of an ATC training weekend. Therapeutic 
Communities ,26
, 6–18.
23. Mahoney, N. (1979). My stay at the Henderson Therapeutic 
Community. In Therapeutic communities: reﬂ  ections and progress
(eds. R.D. Hinshelwood and N. Manning), pp. 76–87. Routledge and Kegan Paul, London.
24. Wexler, H. (1997). Therapeutic communities in American prisons. 
In Therapeutic communities for offenders  (eds. E. Cullen, L. Jones, and

In Therapeutic communities for offenders  (eds. E. Cullen, L. Jones, and 
R. Woodward), pp. 161–79. Wiley, Chichester.
25. Lees, J., Manning, N., and Rawling, B. (1999). Therapeutic community 
effectiveness. A systematic international review of therapeutic community treatment for people with personality disorders and mentally disordered offenders . CRD Report 17, NHS Centre for Reviews and Dissemination, 
University of Y ork, Y ork.
26. Warren, F., Preedy-Fayers, K., McGauley, G., et al. (2003). Review of 
treatments for severe personality disorder . Home Ofﬁ  ce Online Report 
30/03, Home Ofﬁ  ce, London.
27. Rawlings, B. (1999). Therapeutic communities in prisons: a research 
review. Therapeutic Communities ,20, 177–93.
28. Y ates, R. and Wilson, J. (2001). The modern therapeutic community: 
dual diagnosis and the problem of change. In Therapeutic communities

dual diagnosis and the problem of change. In Therapeutic communities 
for the treatment of drug users  (eds. B. Rawlings and R. Y ates). Jessica 
Kingsley Publishers, London and Philadelphia.
29. Leff, J. and Trieman, N. (1997). Providing a comprehensive community 
psychiatric service. In Care in the community: illusion or reality
(ed. J. Leff), pp. 189–201. Wiley, Chichester.6.3.9 therapeutic communities

SECTION 6  treatment methods in psychiatry 1398
30. Sacks, S. (2000). Co-occurring mental and substance use disorders: 
promising approaches and research issues. Substance Use and Misuse ,
35, 2061–93.
31. Rose, M. (1997). Transforming hate to love: an outcome study 
of the Peper Harow treatment process for adolescents . Routledge, 
London.32. Wright, J.C. and Richardson, P . (2003). The challenge of research. 
In Therapeutic communities for children and young people  (eds. A. Ward, 
K. Kasinski, J. Pooley, and A. Worthington), pp.244–53. Jessica Kingsley, 
London.
33. Cox, C. (1995). The case for village communities for people with 
learning disabilities. British Journal of Nursing ,4, 1130–4.

6.4
Treatment by other professions
Contents
 6.4.1 Rehabilitation techniques
W. Rössler
 6.4.2 Psychiatric nursing techniques
 6.4.3 Social work approaches to mental 
health work: international trends
 6.4.4 Art therapy
6.4.1 Rehabilitation techniques
W. Rössler
The goal of psychiatric rehabilitation is to help disabled individuals 
to establish the emotional, social, and intellectual skills needed to
live, learn, and work in the community  with the least amount of 
professional support.(1)
Rehabilitation practice has changed the perception of mental 
illness. Enabling disabled people to live a normal life in the com-munity causes a shift away from a focus on an illness model towards a model of functional disability . As such, other outcome measures

aside from clinical conditions become relevant. Social role func-tioning including social relationship, work, and leisure as well as quality of life and family burden are of major interest for the people affected living in the community.
(25)
The relevance of psychosocial and environmental problems is 
reﬂ ected in the DSM-IV and ICD-10. Axis IV of DSM-IV and codes 
Z55–Z65 and Z73 of ICD-10 are assigned for reporting psychoso-cial and environmental problems that may affect the diagnosis, treatment, and prognosis of mental disorders.The International Classiﬁ  cation of 
Functioning, Disability and Health
Long-term consequences of major mental disorders might be 
described using different dimensions. A useful tool was provided by the International Classiﬁ  cation of Impairment, Disability and 
Handicaps (ICIDH), first published by the World Health Organization in 1980. The ICIDH has been recently revised. The revised ‘ International Classiﬁ  cation of Functioning, Disability

Handicaps (ICIDH), first published by the World Health Organization in 1980. The ICIDH has been recently revised. The revised ‘ International Classiﬁ  cation of Functioning, Disability 
and Health’  (ICF) includes a change from negative descriptions of 
impairments, disabilities and handicaps to neutral descriptions of body structure and function, activities and participation. A further change has been the inclusion of a section on environmental factors as part of the classiﬁ  cation. This is in recognition of the 
importance of the role of environmental factors in either facilitat-ing functioning or creating barriers for people with disabilities. Environmental factors interact with a given health condition to create a disability or restore functioning, depending on whether the 
environmental factor is a facilitator or a barrier.
ICF is a useful tool to comprehend chronically mentally ill in all

ICF is a useful tool to comprehend chronically mentally ill in all 
their dimensions including impairments at the structural or functional level of the body, at the person level concerning 
activity limitations and at the societal level with respect to restric-
tions of participation. Each level encompasses a theoretical foundation on which a respective rehabilitative intervention can be formulated.
Target population
During the course of psychiatric reforms the predominant objec-
tive of psychiatric rehabilitation was to resettle patients from large custodial institutions to community settings. T oday all patients suffering from severe mental illness require rehabilitation. The core group is drawn from patients with the following:
◆ persistent psychopathology
◆ marked instability characterized by frequent relapse
◆ social maladaptation.(28)

SECTION 6  treatment methods in psychiatry 1400
There are other deﬁ  nitions currently used to characterize the 
chronically mentally ill. But they all share some common elements, that is a diagnosis of mental illness, prolonged duration, and role 
incapacity .
Although the majority of the chronically mentally ill have the 
diagnosis of schizophrenic disorders, other patient groups with psy-chotic and non-psychotic disorders are targeted by psychiatric reha-bilitation. Up to 50 per cent of people with severe mental illness carry dual diagnoses  especially in combination with substance abuse.
The role of the psychiatrist in rehabilitation
Psychiatric rehabilitation is by its very nature, multidisciplinary;
because of the many different competencies required. Monitoring medication is a key task of the psychiatrist.
Pharmacotherapy in psychiatric rehabilitation needs some

Pharmacotherapy in psychiatric rehabilitation needs some 
special consideration. Symptom control does not necessarily have the highest priority as some side effects of pharmacological treat-ment can weaken a person’s ability to perform his social roles, and impair vocational rehabilitation. Many patients living in the community want to take responsibility for their medication
themselves. This also includes the varying of medication without consultation within certain limits.
The starting point for an adequate understanding of rehabilita-
tion is that it is concerned with the individual person in the context 
of his or her speciﬁ  c environment. Psychiatric rehabilitation is 
regularly carried out under real life conditions . Thus, rehabilita-

tion practitioners have to take into consideration the realistic life circumstances that the affected persons are likely to encounter in their day-to-day living.
A necessary second step is helping disabled persons to identify 
their personal goals . Motivational interviews provide a sophisti-
cated approach to identify the individuals’ personal costs and beneﬁ  ts associated with the needs listed.
(8) This makes it also nec-
essary to assess the individuals’ readiness for change.(15) Functional 
assessment and individual goal setting are prerequisites of a differ-entiated rehabilitation intervention plan and should be repeated in different stages of the rehabilitation process.
The rehabilitative planning process focuses on the patient’s 
strengths . Irrespective of the degree of psychopathology of a given

strengths . Irrespective of the degree of psychopathology of a given 
patient, the rehabilitation practitioner must work with the ‘well 
part of the ego’  as ‘there is always an intact portion of the ego to 
which treatment and rehabilitation efforts can be directed’ (Lamb 1984
(2)). This leads to a closely related concept: the aim of restoring 
hope to people who suffered major setbacks in self-esteem because of their illness. As Bachrach
(2) states ‘it is the kind of hope that 
comes with learning to accept the fact of one’s illness and one’s limitations and, proceeding from there’ .
Psychiatric rehabilitation concentrates on peoples’ rights as 
a respected partner  and endorses their involvement and self-
determination  concerning all aspects of the treatment and reha-
bilitation process. These rehabilitation values are also incorporated in the concept of recovery.
(9) Within the concept of recovery, the

(9) Within the concept of recovery, the 
therapeutic alliance  plays a crucial role in engaging the patient in 
his or her own care planning. It is essential that the patient can rely on his or her therapist’s understanding and trust as most of the chronically mentally ill and disabled persons lose close, intimate, and stable relationships in the course of the disease. Recent research has suggested that social support is associated with recovery from chronic diseases, greater life satisfaction, and enhanced ability to 
cope with life stressors.
(24) Therefore, psychiatric rehabilitation is 
also an exercise in network building.
Current approaches
Psychiatric rehabilitation aims at changing the natural course

of the disease. Y et, there is no consensus among rehabilitation researchers on what rehabilitation actually does accomplish. Some understand rehabilitation as an approach to help disabled people to compensate for impairments and to function optimally with the deﬁ ciencies they have. Other researchers assume that rehabilitation 
helps the patient to recover from the disorder itself, while the contributing factors to the healing process are not clear.
The overall philosophy of psychiatric rehabilitation comprises 
two intervention strategies. The ﬁ  rst strategy is individual-centered 
and aims at developing the patient’s skill  to interact with a stress-
ful environment. The second strategy is ecological and is directed towards developing environmental  resources to reduce potential

ful environment. The second strategy is ecological and is directed towards developing environmental  resources to reduce potential 
stressors. Most disabled people need a combination of both approaches.
As a general rule people with psychiatric disabilities tend to 
have the same life aspirations  as people without disabilities in 
their society or culture. They want to be respected as autono-mous individuals and lead a life as normal as possible. As such they mostly desire (1) their own housing, (2) an adequate education and a meaningful work career, (3) satisfying social and intimate relationships, and (4) participation in community life with full rights.
Housing
The objective of psychiatric reforms since the mid-50s of the 20th

Housing
The objective of psychiatric reforms since the mid-50s of the 20th 
century has been to resettle chronically mentally ill persons from large custodial institutions to community settings. Providing sheltered housing in the community for the long-term patients of the old asylums was one of the ﬁ  rst steps in the process of deinsti-
tutionalization. Most long-stay patients can successfully leave 
psychiatric hospitals and live in community settings .
Ideally, a residential continuum  (RC) with different housing 
options should be provided. RC ranges from round-the-clock staffed sheltered homes to more independent and less staffed sheltered apartments, which eventually allow individuals moving to independent housing in the community. Critics of RC contended that (1) up to date RC is rarely available in communities, (2) that RC does not meet the varying and ﬂ  uctuating needs of persons 
with serious mental illnesses, and (3) that RC does not account for

with serious mental illnesses, and (3) that RC does not account for 
individuals’ preferences and choices. Supported housing , i.e. inde-
pendent housing coupled with the provision of support services emerged in the 1980s as an alternative to RC. Supported housing offers ﬂ  exible and individualized services depending on the individ-
ual’s demands. In the meantime, rehabilitation research could dem-onstrate that supported housing is a realistic goal for the majority of people with psychiatric disabilities.
(23) Once in supported housing, 
the majority stay in housing and are less likely to become hospital-ized. Other outcomes do not yield consistent results.
Work
The beneﬁ  cial effects of work on mental health have been known 
for centuries.(11) Therefore, vocational rehabilitation  has been

1401
a core element of psychiatric rehabilitation since its beginning. 
Vocational rehabilitation is based on the assumption that work not only improves activity, social contacts, etc., but may also promote gains in related areas such as self-esteem and quality of life, as work and employment are a step away from dependency and a step closer  to integration into society. Enhanced self-esteem  in turn improves 
adherence to rehabilitation of individuals with impaired insight.
Vocational rehabilitation originated in psychiatric institutions 
where the lack of activity and stimulation led to apathy and with-drawal of their inpatients. Long before the introduction of medica-tion, occupational and work therapy contributed to sustainable improvements in long-stay inpatients. T oday occupational and work therapy are not any longer hospital-based but represent the starting point for a wide variety of rehabilitative techniques teach-ing vocational skills.

Vocational rehabilitation programs in the community provide a 
series of graded steps to promote job entry or re-entry . For less dis-
abled persons, brief and focused techniques are used to teach how they can ﬁ  nd a job, ﬁ  ll out applications, and conduct employment 
interviews. In transitional employment, a temporary work environ-ment is provided to teach vocational skills, which should enable the affected person to move on to competitive employment. But all too 
often, the gap between transitional and competitive employment is 
so wide that the mentally disabled individuals remain in a temporary work environment. Sheltered workshops providing pre-vocational training also quite often prove a dead end for the disabled persons.
One consequence of the difﬁ  culties in integrating mentally

One consequence of the difﬁ  culties in integrating mentally 
disabled individuals into the common labour market has been the steady growth of cooperatives, which operate commercially with disabled and non-disabled staff working together on equal terms and sharing in management. The mental health professionals work in the background providing support and expertise.
T oday, the most promising vocational rehabilitation model is 
supported employment  (SE). In SE, disabled persons are placed in 
competitive employment according to their choices as soon as pos-sible, and receive all support needed to maintain their position.
(4)
The support provided is continued indeﬁ  nitely. Participation in SE 
programs is followed by an increase in the ability to ﬁ  nd and keep 
employment.(7) Links were also found between job tenure and 
non-vocational outcomes, such as improved self-esteem, social integration, relationships, and control of substance abuse.
(4,29)  It

(4,29)  It 
was also demonstrated that those who had found long-term employment through SE had improved cognition, quality of life, and better symptom control.
(17)
Although ﬁ  ndings regarding SE are encouraging, some critical 
issues remain to be answered. Many individuals in SE obtain unskilled part-time jobs. Since most studies only evaluated short (12–18 months) follow-up periods, the long-term impact remains unclear. Currently, we do not know which individuals beneﬁ  t from 
supported SE and which do not.
(20) After all, we have to realise that 
the integration into the labour market does by no means only depend on the ability of the persons affected to fulﬁ  ll a work role

the integration into the labour market does by no means only depend on the ability of the persons affected to fulﬁ  ll a work role 
and on the provision of sophisticated vocational training and sup-port techniques but also on the willingness of society to integrate
its most disabled members.
Building relationships
In recent years, social skills training packaged in the form of modules with different topics has become very popular and has been widely promulgated. The modules focus on medication man-
agement, symptom management, substance abuse management, basic conversational skills, interpersonal problem solving, friend-ship and intimacy, recreation and leisure, workplace fundamentals, community (re-)entry, and family involvement. Each module is composed of skill areas. The skills areas are taught in exercises with demonstration videos, role-play and problem solving exercises, and in-vivo  and homework assignments.
(14)

(14)
The results of several control studies suggest that disabled 
individuals can be taught a wide range of social skills . Social and 
community functioning improve when the trained skills are rele-vant for the patient’s daily life, and the environment perceives and reinforces the changed behaviour. Unlike medication effects, bene-ﬁ ts from skills training occur more slowly. Furthermore, long-term 
training has to be provided for positive effects.
(3) Overall, social 
skills training have been shown to be effective in the acquisition and maintenance of skills and their transfer to community life.
(13)
Keeping relationships
As a consequence of deinstitutionalization the burden of care  has 
increasingly fallen on the relatives of the mentally ill. Informal caregiv-ing signiﬁ  cantly contributes to health care and rehabilitation.
(31)
Fifty to ninety per cent of disabled persons live with their relatives

(31)
Fifty to ninety per cent of disabled persons live with their relatives 
following acute psychiatric treatment. This is a task many families do not choose voluntarily. Caregiving imposes a signiﬁ  cant burden 
on families. Those providing informal care face considerable adverse health effects, including higher levels of stress and depres-sion, and lower levels of subjective well being, physical health and self-efﬁ  cacy. Additionally, not all families are equally capable of 
giving full support to their disabled member and are not willing to replace an insufﬁ  cient health care system. Caregivers regularly 
experience higher levels of burden when they have poor coping resources and reduced social support. But families also represent 
support systems , which provide natural settings for context-
dependent learning important for recovery of functioning. As such, there has been a growing interest in helping affected families since the beginning of care reforms.

One area of interest deals with the expectations of relatives 
concerning the provision of care. Relatives quite often feel ignored ,
not taken seriously, and also feel insufﬁ  ciently informed by health 
professionals. They also may feel that their contribution to care is not appreciated or that they will be blamed for any patient problems. It certainly is no surprise that there is a lot of frustration and resentment among relatives considering the physical, ﬁ  nancial 
and emotional family burden.
Family intervention programs  have produced promising results. 
Family intervention is effective in lowering relapse rate, and also in improving outcome e.g., psychosocial functioning. Possibly, family intervention can reduce family burden. Furthermore, the treatment gains are fairly stable.

(21) But we also have to appreciate, that it is 
not clear what the effective components of the different models are. Additionally, family interventions differ in frequency and length of treatment. There are also no criteria for the minimum amount of treatment necessary.
Finally, we have to be aware that most family interventions were 
developed in the context of western societies during deinstitution-alization. Family caregiving might be quite different in a different 
cultural context . This refers to other cultures in total as well as to 
minority groups in western societies.
(31)6.4.1 rehabilitation techniques

SECTION 6  treatment methods in psychiatry 1402
Participation in community life with full rights
Practitioners often are confronted with the deleterious effects of 
stigma and discrimination  in the lives of people with serious 
mental illnesses. Numerous studies have examined stigmatizing attitudes toward people with mental illness.
(12) In recent years, the 
scientiﬁ  c interest in the perspective of the labelled individual has 
increased too. There is extensive empirical evidence of the negative consequences of labelling and perceived stigmatization. These include demoralization, low quality of life, unemployment, and reduced social networks.
(10,19) Once assigned the label ‘mental 
illness’ and having become aware of the related negative stereo-types, the affected individuals expect to be rejected, devaluated or discriminated against. This vicious cycle decreases the chance of recovery and normal life.
On the other hand, well-integrated people with mental illness

On the other hand, well-integrated people with mental illness 
exhibit better outcomes regarding psychopathology and quality of life. The importance of social integration is underlined even more when considering the subjective availability of support: perceived social support predicts outcome in terms of recovery from acute episodes of mental illness, community integration, and quality of life.
(27, 30)
On the basis of comprehensive research in this area during the 
last decade, several strategies have been developed to ﬁ  ght the 
stigma and discrimination suffered by those who have mental ill-nesses.
(30) Different research centres developed interventions 
directed to speciﬁ  c target groups relevant for de-stigmatization, 
e.g., students(18) or police ofﬁ  cers.(22) Persons in contact with 
mentally ill individuals quite often have a more positive attitude. Contact with the mentally ill persons also reduces social distance,
(12)

(12)
which is a strong argument in favour of community psychiatry. Other initiatives have targeted stigma by means of more compre-hensive programs. The World Psychiatric Association launched one of the internationally best-known programs in 1996 (www.openthedoors.com). All these initiatives make clear that efforts in re-integrating persons with serious mental illness into community life must be accompanied by measures on the societal level.
The core elements of modern psychiatric rehabilitation are 
summarized in Box 6.4.1.1
Developing environmental resources
Effective psychiatric rehabilitation requires individualized and 
specialized treatment , which has to be embedded in a comprehen-
sive and coordinated system of rehabilitative services. But even when a variety of services are available, they are poorly linked in

sive and coordinated system of rehabilitative services. But even when a variety of services are available, they are poorly linked in 
many cases, and costly duplication may occur.
While developing community support systems it became 
obvious that there is a need to coordinate and integrate the 
services  provided as each involved professional concentrates on 
different aspects of the same patient. Therefore, as a key coordinat-ing and integrating mechanism, the concept of case management
(CM) originated. CM focuses on all aspects of the physical and social environment. The core elements of CM are the assessment of patients’ needs, the development of comprehensive service plans for the patients, and arrangement of service delivery.
(26)
Over the past two decades, a variety of different models of CM

(26)
Over the past two decades, a variety of different models of CM 
have been developed which exceed the original idea that CM mainly intends to link the patient to needed services and to coordinate those services. T oday most clinical case managers also provide direct services in the patient’s natural environment. This model is called Intensive Case Management  (ICM). ICM on its part is difﬁ  cult to 
distinguish from Assertive Community Treatment  (ACT).
Stein and T est have developed the basic compounds of ACT in 
the 1970’s.
(33) The original program was designed as a community 
based alternative to hospital treatment for persons with severe mental illnesses. A comprehensive range of treatment, rehabilita-tion, and support services in the community is provided through a multidisciplinary team. ACT is characterized by an assertive outreach approach i.e., interventions are mainly provided in the natural environment of the disabled individuals.
(32)

(32)
Research on CM and ACT yielded ‘mixed’ results.(6) While the 
traditional ofﬁ  ce-based CM approach obviously is less successful, 
the ACT model was found to be more beneﬁ  cial when compared 
with standard care.(16) ACT can reduce time in hospital,(20) but has 
moderate or only little effects on improving symptomatology and social functioning. The differing features of the respective services might explain the international variation. Six regularly occurring features of successful services were identiﬁ  ed: smaller case loads, 
regularly visits at home, a high percentage of contacts at home, responsibility for health and social care, multidisciplinary teams, and a psychiatrist integrated in the team.
(5)
1. Anthony, W. (1979). The principles of psychiatric rehabilitation .
University Park Press, Baltimore, MD.
2. Bachrach, L.L. (2000). Psychosocial rehabilitation and psychiatry in the 
treatment of schizophrenia – what are the boundaries? Acta Psychiatr

treatment of schizophrenia – what are the boundaries? Acta Psychiatr 
Scand Suppl 407, 6–10.
3. Bellack, A.S. (2004). Skills training for people with severe mental illness. 
Psychiatr Rehabil J ,27(4): 375–91.
4. Bond, G.R. (2004). Supported employment: evidence for an evidence-
based practice. Psychiatr Rehabil J ,27(4): 345–59.
5. Burns, T, Catty, J, Wright, C. (2006). De-constructing home-based care 
for mental illness: can one identify the effective ingredients? Acta Psychiatr Scand Suppl ,429, 33–5.
6. Burns, T, Fioritti, A, Holloway, F. et al. (2001). Case management and 
assertive community treatment in Europe. Psychiatr Serv ,52(5), 631–6.
7. Cook, J.A., Leff, H.S., Blyler, C.R. et al. (2005). Results of a multisite 
randomized trial of supported employment interventions for individuals with severe mental illness. Arch Gen Psychiatry,
62(5), 505–12.

8. Corrigan, P .W., McCracken, S.G., Holmes, E.P . (2001). Motivational 
interviews as goal assessment for persons with psychiatric disability. Community Ment Health J ,37(2), 113–22.Box 6.4.1.1 Core elements of psychiatric rehabilitation
– multidisciplinary– carried out under real life conditions
– identify patient’s personal goals
– focus on the patient’s strengths– work with the ‘well part of the ego,– concentrate on people’s rights as a respected partner– endorse their involvement and self-determination– build a therapeutic alliance

1403
 9. Farkas, M., Gagne, C., Anthony, W. et al. (2005). Implementing 
recovery oriented evidence based programs: identifying the critical 
dimensions.  Community Ment Health J, 41(2), 141–58.
10. Graf, J., Lauber, C., Nordt, C. et al. (2004). Perceived stigmatization of 
mentally ill people and its consequences for the quality of life in a Swiss population. J Nerv Ment Dis ,192(8), 542–7.
11. Harding, C., Strauss, J., Hafez, H. et al.  (1987). Work and mental 
illness. I. T oward an integration of the rehabilitation process. Journal of 
Nervous and Mental Disease ,175, 317–26.
12. Lauber, C., Nordt, C., Falcato, L. et al. (2004). Factors inﬂ  uencing social 
distance toward people with mental illness. Community Ment Health J ,
40(3), 265–74.
13. Liberman, R.P ., Glynn, S., Blair, K.E. et al. (2002). In vivo ampliﬁ  ed 
skills training: promoting generalization of independent living skills for clients with schizophrenia. Psychiatry, 65(2), 137–55.

14. Liberman, R.P ., Kopelowicz, A. (2002). T eaching persons with severe 
mental disabilities to be their own case managers. Psychiatr Serv 53(11), 
1377–9.
15. Liberman, R.P ., Wallace, C.J., Hassell, J. (2004). Rehab rounds: 
Predicting readiness and responsiveness to skills training: the Micro-Module Learning T est. Psychiatr Serv ,55(7), 764–6.
16. Marshall, M. (1996). Case management: a dubious practice. 
BMJ, 312(7030), 523–4.
17. McGurk, SR., Mueser, K.T. (2003). Cognitive functioning and 
employment in severe mental illness. J Nerv Ment Dis ,191(12), 789–98.
18. Meise, U., Sulzenbacher, H., Kemmler, G. et al. (2000). [‘‘…not dangerous, 
but nevertheless frightening’’ . A program against stigmatization of 
schizophrenia in schools]. Psychiatr Prax , 27(7), 340–6.
19. Mueller, B., Nordt, C., Lauber, C. et al. (2006). Social support modiﬁ  es

19. Mueller, B., Nordt, C., Lauber, C. et al. (2006). Social support modiﬁ  es 
perceived stigmatization in the ﬁ  rst years of mental illness: 
a longitudinal approach. Soc Sci Med  2006, 62(1), 39–49.
20. Mueser, K.T., Bond, G.R., Drake, R.E. et al.  (1998). Models of 
community care for severe mental illness: a review of research on case management. Schizophrenia Bulletin ,24, 37–74.
21. Pilling, S., Bebbington, P ., Kuipers, E. et al. (2002). Psychological 
treatments in schizophrenia: I. Meta-analysis of family intervention and cognitive behaviour therapy. Psychol Med ,32(5), 763–82.
22. Pinfold, V ., Huxley, P ., Thornicroft, G. 
et al. (2003). Reducing 
psychiatric stigma and discrimination–evaluating an educational 
intervention with the police force in England. Soc Psychiatry Psychiatr 
Epidemiol ,38(6), 337–44.
23. Rog, DJ. (2004). The evidence on supported housing. Psychiatr Rehabil J,
27(4), 334–44.

24. Rogers, E.S., Anthony, W., Lyass, A. (2004). The nature and dimensions 
of social support among individuals with severe mental illnesses. 
Community Ment Health J ,40(5), 437–50.
25. Rössler, W. (2006). Psychiatric rehabilitation today: an overview. 
World Psychiatry 5(3), 151–7.
26. Rössler, W., Fätkenheuer, B., Löfﬂ  er, W. et al. (1992). Does case 
management reduce the rehospitalization rate? Acta Psychiatrica 
Scandinavica ,86, 445–9.
27. Rössler, W., Salize, H.J., Cucchiaro, G. et al. (1999). Does the place of 
treatment inﬂ  uence the quality of life of schizophrenics? Acta Psychiatr 
Scand ,100(2), 142–8.
28. Royal College of Psychiatrists (1996). Psychiatric rehabilitation  (revised 
edition). Gaskell, London.

29. Ruesch, P ., Graf, J., Meyer, P .C. et al. 2004). Occupation, social support 
and quality of life in persons with schizophrenic or affective disorders. Soc Psychiatry Psychiatr Epidemiol ,39(9), 686–94.
30. Rusch, N., Angermeyer, M.C., Corrigan, P .W. (2005). Mental illness 
stigma: concepts, consequences, and initiatives to reduce stigma. Eur Psychiatry, 20(8), 529–39.
31. Schulze, B., Rössler, W. (2005). Caregiver burden in mental illness: 
review of measurement, ﬁ  ndings and interventions in 2004–2005. 
Current Opinion in Psychiatry ,18, 684–91.32. Scott, J.E. and Dixon, L.B. (1995). Assertive community treatment 
and case management for schizophrenia. Schizophrenia Bulletin ,
21, 657–68.
33. Stein, L.I. and T est, M.A. (1980). Alternative to mental hospital

33. Stein, L.I. and T est, M.A. (1980). Alternative to mental hospital 
treatment. I. Conceptual model, treatment program, and clinical evaluation. Archives of General Psychiatry ,37, 392–7.
6.4.2 Psychiatric nursing 
techniques
Psychiatric nursing as an entity has really only evolved since the 
Second World War. Psychiatric nurses (now often referred to as mental health nurses in the United Kingdom and Australasia) can now be found in most countries of the developed world, although in the developing world, psychiatric nursing is still not deﬁ  ned as a 
speciﬁ  c discipline. In many countries, psychiatric hospitals are still 
staffed by untrained ‘Attendants’ who may have some supervision from general trained nurses. Nevertheless, a number of initiatives, notably those of the Geneva Initiative in Psychiatry
(1) in Eastern

(1) in Eastern 
Europe and the former Soviet Union and the World Health Organization in African countries, have provided speciﬁ  c training 
in psychiatric nursing techniques.
The development of psychiatric nursing across the world needs 
to be seen in the context of changing and evolving patterns of mental health care. De-institutionalization, with the attendant setting up of community mental health teams, has prompted a range of innovations in psychiatric nursing and the psychiatric nurse of today, who in the United States and Europe is likely to be a university graduate, is a very different person to that of the nurse working in the post-Second World War asylums of 40 years ago.
In this chapter, we examine the development of psychiatric nurs ing 
in some detail and particularly emphasize the role of psychiatric 
nurses working in the community. Community psychiatric nursing 
ﬁ rst developed in the United Kingdom nearly 50 years ago and

ﬁ rst developed in the United Kingdom nearly 50 years ago and 
this model has been followed in countries such as Australia and New Zealand. However, this community role has not developed to any great extent in the United States, where the main presence of psychiatric nursing remains in hospital-based care. Furthermore, in the United Kingdom and Australasia, the development of com-munity initiatives has seen the role of the psychiatric nurse blur-ring with that of other mental health professionals. Chapters such as this cannot really do justice to the whole range of techniques used by psychiatric nurses; neither can it examine in any detail the differences between psychiatric nursing practices across the world. However, a description of psychiatric nursing in six important areas will provide the reader with an appreciation of the range and diversity of psychiatric nursing skills:
◆ Inpatient care

◆ Psychosocial interventions in the community
◆ Prescribing and medication management6.4.2 psychiatric nursing techniques

SECTION 6  treatment methods in psychiatry 1404
◆ Cognitive behaviour therapy
◆ Primary care
◆ Psychiatric nursing in the developing world.
Psychiatric nursing in inpatient settings
In the past three decades the population in psychiatric hospitals 
across the developed world has fallen dramatically in England from 160 000 to 30 000 beds over a period of 25 years and the duration of inpatient care in the United Kingdom in 2007 is approximately 36 days. However, today’s inpatients are a population with much greater levels of illness than was previously the case; they tend to be more treatment-resistant, have complex problems, and display high levels of substance abuse and violence.
(2) As a corollary of this,

(2) As a corollary of this, 
a greater proportion of patients are now detained under mental health legislation. Inpatient facilities consist of acute psychiatric units, local secure units, and high secure psychiatric hospitals for those patients who pose high levels of danger to themselves and others. In the United Kingdom, four high secure hospitals contain approximately 1600 patients. It should also be noted that, due to the large numbers of people with psychiatric problems in prisons, there are now several hundred psychiatric nurses employed in prison settings to carry out a range of assessment and treatment procedures. In addition, the NHS also has a number of ‘in reach’ schemes, which include sending NHS staff into prisons on a sessionalbasis.
Given that community care in the western World is now the 
norm, inpatient care is now seen as a short-term measure with the

norm, inpatient care is now seen as a short-term measure with the 
dual purposes of stabilizing the patient’s condition and keeping the patient safe. Psychiatric nurses have a role to play in the overall assessment of the patient and, given that the nurse is—literally—with the patient 24 h a day, the observation of the patient’s mental state and behaviour is of considerable importance. Unfortunately, this is an area where, outside the United States, a number of prob-lems exist and suicide rates by inpatients are unacceptably high.
(3)
In the United States, inpatient wards tend to be much more secure than wards in countries such as the United Kingdom and Australia and, therefore, the incidence of inpatient suicide is much lower. The UK National Conﬁ  dential Inquiry into suicides and homicides
(3)
demonstrates that nearly 200 suicides by inpatients occur every

(3)
demonstrates that nearly 200 suicides by inpatients occur every 
year, with hanging on the ward itself being still prevalent at unaccept-ably high levels. Recently the National Institute for Health and Clinical Excellence (NICE)
(4) has published guidelines, which 
include the observation of patients at risk. This guidance sets out very careful protocols for the observation of patients at risk and includes recommendations regarding the prevention of abscond-ing. In the United Kingdom and Australia, open-door policies still operate in acute psychiatric units and it is being increasingly recog-nized that balancing the rights of the patients against safety is a difﬁ cult issue. Nurses also have a major role to play in providing 
patients and their families with information about condition and treatment. We also know that there are interventions that can be 
applied by nurses, which would lead to improved outcomes. For 
example, Drury et al.

(5) showed that a cognitive behavioural therapy 
package improved longer-term outcomes. Similarly, Kemp et al.(6)
showed that motivational interviewing and psychoeducation 
methods produced clear, clinical, and economic beneﬁ  ts in patients 
who have compliance problems with medication.With regard to the containment of violent behaviour, which is 
now so common in inpatient settings, nurses in the United Kingdom have been assisted by very comprehensive evidence-based guidance from the National Institute for Health and Clinical Excellence (NICE),
(4) which sets out clear guidance on the use of

(4) which sets out clear guidance on the use of 
de-escalation techniques and control and restraint, as well as pro-viding a comprehensive algorithm for the use of rapid tranquilliza-tion. In respect of rapid tranquillization, nurses are now provided with the necessary skills to observe and monitor patients following rapid tranquillization, including the use of pulse oximetry and blood pressure. Whilst nurses in Australasia use the same methods of managing violent behaviour as nurses in the United Kingdom, psychiatric nurses in most European countries and in the United States use various forms of mechanical restraint and a very wide range of devices, including belts, straps, nets, and jackets. Whilst it needs to be recognized that there are a range of social and cultural inﬂ uences that determine how violence in mentally ill people is 
managed, it is important to note that the evidence base for all forms of violence management, including rapid tranquillization, is very

managed, it is important to note that the evidence base for all forms of violence management, including rapid tranquillization, is very 
poor and a Cochrane review found that there is no evidence base 
for the use of seclusion and restraint.
(7)
Psychosocial interventions 
in the community
In order to appreciate the current practice of psychiatric nurses

(7)
In order to appreciate the current practice of psychiatric nurses 
working in the community, it is important to say something about the historical context. Until the early 1980s, community psychiatric nurses (CPNs) in the United Kingdom were generally based in large, Victorian psychiatric hospitals and worked mostly within a consultant psychiatrist team responsible for the follow-up of patients after discharge from hospital. Their main responsibilities were the administration of medication and the provision of general, supportive care, mostly to people with schizophrenia, the elderly with functional and organic illnesses, and to people with other serious and enduring mental illnesses. Initial research on the effectiveness of community psychiatric nurses produced very positive results. In a randomized trial conducted by Paykel et al.
(8)

(8)
CPNs were compared with psychiatric registrars in the provision 
of aftercare for patients who had suffered an acute episode requiring hospitalization. In general terms, this study showed that there was an equivalent outcome on clinical, social, and economic measures. Some 20 years ago, CPNs in the United Kingdom began to diversify their practice and separated themselves from consultant psychia-trists, attaching themselves to primary care settings and taking referrals directly from GPs. By 1990, a national survey showed that 40 per cent of CPNs worked in primary care.
(9) The vast majority 
of this work involved treating people with depression, anxiety, and adjustment disorder, using counselling-based approaches. Whilst this work by CPNs became very popular with GPs and mental health professionals in general, research into the effectiveness of their work demonstrated that they were largely ineffective. Gournay and Brooking
(10) carried out a randomized controlled trial involv-

ing 11 CPNs, working in six primary care settings in North London. In this study, 177 patients were randomized to either routine continuing care from their GP or to CPN intervention. The major-ity of patients had adjustment disorders and various states of general depression and anxiety. Patients, in both the CPN and

1405
continuing GP care groups, showed signiﬁ  cant improvement on a 
range of measures, clinical status, and social functioning but, at post-treatment and follow-up, there was no difference in outcomes demonstrated. Patients allocated to CPNs showed high levels of dropout (50 per cent) and patient satisfaction rating did not correlate with outcome measures. An economic analysis
(11) showed 
that, per unit of health gain, CPN intervention was very expensive compared with interventions for people with schizophrenia. The Paykel and Gournay and Brooking studies still represent the only research evidence regarding the efﬁ  cacy of CPNs working with 
common mental disorders.
During the early 1990s a National Review of Psychiatric Nursing

During the early 1990s a National Review of Psychiatric Nursing 
in the United Kingdom led to CPNs refocusing their efforts on the seriously mentally ill and this trend has been followed in Australasia. In the last decade there has been a wide range of psychiatric nursing developments in respect of psychosocial interventions. The initial impetus for this development came from the Thorn Programme, this initiative taking its name from the Sir Jules Thorn Trust, a charitable foundation that provided the funds to inaugu-
rate the ﬁ  rst 3 years of the training programme for nurses, com-
mencing in 1992. The initiative was originally led by Dr Jim Birley who, with a group of colleagues from other professions, became impressed by the work of nurses working in cancer care. Birley’s initial aim was to train a substantial number of nurses speciﬁ  cally

dedicated to the care of people with schizophrenia and their relatives. Indeed, Birley, who was one of the pioneers of Social Psychiatry in the United Kingdom, noted that the families of people with schizophrenia were often in great need of intervention. Previous work in Manchester
(12) had conﬁ  rmed that nurses could 
be trained in family intervention skills which in turn led to positive outcomes for the patient and family. This training in family work formed the basis of what has now become a more general initiative to train nurses in various evidence-based psychosocial interven-tions for schizophrenia. The Thorn Initiative has now become the national model of training in psychosocial interventions in the United Kingdom and similar programmes to Thorn have been set-up in Australasia and some European countries. The psychosocial interventions used by nurses are as follows:
◆ Assertive community treatment
◆ Family interventions for schizophrenia

◆ Cognitive behavioural techniques for managing hallucinations 
and delusions
◆ Approaches with dual diagnosis
◆ Medication management.
In addition to psychosocial interventions, training programmes 
for psychiatric nurses working in the community, now also include approaches to improve the physical health of people with serious mental health problems and nurses are now taking a more active lead in ensuring that this very vulnerable population obtains appropriate medical services including physical screening and health promotion activities. At the time of writing, there are also, in several parts of the United Kingdom, speciﬁ  c training programmes 
for nurses aimed at helping patients with chronic mental illness to deal with obesity, lack of exercise, and smoking.
On a cautionary note, there are now several studies
(13) which dem-

onstrate that more intensive case management may not be effective, the possible reason being that one needs to provide nurses with 
suitable levels of training in community approaches. In the UK700 study
(13) mentioned above the nurses involved only received a few 
hours training in case management approaches, whist nurses

hours training in case management approaches, whist nurses 
undertaking basic psychosocial interventions training such as a Thorn diploma will receive 250 h of classroom instruction in addi-tion to supervised practice. Whilst there have been considerable numbers of nurses trained in the above-mentioned evidence-based psychosocial interventions, unfortunately there are still many nurses working in the community without such training. Whilst their general psychiatric nursing skills will be reasonably sound, their impact on patient care will be somewhat limited.
In the early part of the twenty-ﬁ  rst century, psychiatric nurses

In the early part of the twenty-ﬁ  rst century, psychiatric nurses 
working in the United Kingdom, Europe, and Australasia are increasingly working in specialist community teams, for example, assertive outreach services, early intervention teams and crisis intervention, and home treatment teams. Whilst these approaches are commonly used across the United States, such teams are likely to be staffed by case managers who have backgrounds in social work and social care and psychiatric nurses are unlikely to be employed in large numbers. In the United States, psychiatric nurses are often speciﬁ  cally employed to run medication clinics, probably 
for reasons of cost, whilst in the United Kingdom, approximately 50 per cent of community mental health teams carrying out a very wide range of psychosocial functions are likely to be CPNs.
Prescribing and medication management
The work of Kemp et al .(6) who showed that motivational inter-

viewing and psychoeducation methods produced good outcomes for patients who were non-compliant with their medication, led to the development of medication management training for nurses in the United Kingdom. Gray et al .
(14) using a cluster randomized 
controlled trial, where 60 CPNs were randomly assigned to medi-cation management training or carrying on with their usual treat-ment as usual, demonstrated that the nurses who had received medication management training produced very clear beneﬁ  ts in 
patients with schizophrenia. The study demonstrated a signiﬁ  cantly

patients with schizophrenia. The study demonstrated a signiﬁ  cantly 
greater reduction in patients’ overall psychopathology for the trained group, compared with treatment as usual. At the end of the 6-month study period, the improvement in positive and negative symptoms for the trained nurses over the control was statistically and clinically signiﬁ  cant. This training is now used by, literally, 
thousands of nurses in the United Kingdom, Australasia, and some non-English speaking countries in Europe. Whilst this training, which comprised a number of components, including improving 
the pharmacological knowledge of the nurses, the use of side effect

the pharmacological knowledge of the nurses, the use of side effect 
monitoring and motivational interviewing for non-compliant patients, a European multi-centre trial, which tested adherence therapy as a treatment package over and above routine clinical care and delivered mostly by psychologists and psychiatrists, showed that the treatment package was no more effective than health edu-cation in improving quality of care.
(15) Both studies raised a num-
ber of questions concerning the very complex issue of treatment compliance with medication and the speciﬁ  c difﬁ  culties associated 
with measurement of compliance itself and of patient insight.
Arguably, the most important recent development in psychiatric 
nursing has been the advent of nurse prescribing. This began more than a decade ago in the United States, where nurses have 6.4.2 psychiatric nursing techniques

SECTION 6  treatment methods in psychiatry 1406
prescriptive authority in virtually all states. The situation in the 
United States is, however, complex with a considerable variation in the level of prescriptive authority across the United States from complete independence to being able to prescribe under a physi-cian protocol. In turn, the educational requirement for nurse prescribers also varies considerably. However, most states have fairly comprehensive regulations concerning not only course content, but also hours of instruction and supervision. The Website of the American Psychiatric Nurses,
(16) provided at the end of this 
chapter, provides very detailed state-by-state information. In 2006, United Kingdom legislation was passed that means nurses may prescribe almost independently,
(17) although—as in the United

(17) although—as in the United 
States—there is a variation across the country in terms of training and practice. Across nursing more generally, the law in the United Kingdom means that provided it is within their area of specialist work, nurses may independently prescribe any drug (including controlled substances such as opiates). By contrast to the different legislative frameworks that exist in the United States, the legislative framework for the United Kingdom is unitary. However, interpre-tation of that framework in the United Kingdom seems to vary between NHS services. There are now similar nurse prescribing ini-tiatives in Australasia, where because of the nature of rural and remote populations, the development of nurse prescribing seems very logical.
At present, there are no randomized controlled trial data to com-

pare nurse prescribing with more conventional doctor prescribing, 
neither is there any substantial data on patient efﬁ  cacy. The advan-
tages of nurse prescribing have been clearly set out in a Maudsley 
discussion paper  by Gournay and Gray
(18) and these include the del-
egation of routine prescribing tasks to nurses, so that psychiatrists may concentrate their prescribing efforts on difﬁ  cult-to-manage 
patients who may be treatment-resistant and/or non-compliant and those patients who have substantial physical health co-morb idity. 
Another advantage might be that CPNs, who are case managers, may be able to spend more time than their psychiatrist colleagues in the detailed evaluation of effectiveness and side effect monitor-ing and management.

For more than 35 years, nurses in the United Kingdom have been trained to provide psychological treatment to patients with various mental health problems. These developments began in 1972, when Isaac Marks, a psychiatrist working at the Maudsley hospital, began a 3-year experiment to determine whether nurses could be trained to deliver behavioural interventions for neurotic disorder. Isaac Marks was one of the ﬁ  rst to recognize that the workforce of 
psychologists would be insufﬁ  cient to deliver evidence-based treat-
ment. Subsequently, Marks
(19) published data which demonstrated 
both the clinical and economic effectiveness of nurses working with neurotic disorders in primary care. Over the years, training programmes for nurses have developed and now nurses are trained in a variety of university and clinical settings alongside their psy-chology colleagues in the practice of evidence-based psychological

treatments, i.e. cognitive behaviour therapy for a very wide range 
of disorders. Whilst the original efforts to train nurses were centred on techniques for the treatment of phobias and obsessive–compulsive disorder, nurses are now trained more comprehensively in cogni-tive behavioural methods, which encompass treatment techniques used in the treatment of depression, schizophrenia, and personality 
disorders. In recent years there has been a small, but signiﬁ  cant, 
growth in the United Kingdom of psychiatric nurses employed as psychological therapists. However, this trend has not been repli-cated in Australasia or Europe, where legislative frameworks pre-vent nurses from obtaining full accreditation as psychological ther-apists. In the United States, the situation is variable. Nevertheless, the American Psychiatric Nurses’ Association membership com-prises a signiﬁ  cant number of nurses who have full accreditation

as therapists in their respective states. Such nurses are now often prepared at a post-doctoral level and their expertise is arguably equivalent to that of their clinical psychologist colleagues.

Following the refocus of CPNs efforts on people with schizophrenia and other serious and enduring illnesses, there have recently been a number of United Kingdom policy developments that will lead to more psychiatric nurses being employed in primary care settings. This trend follows the recognition that many people with common mental health problems do not receive evidence-based treatment or, if they do, they are subject to long periods on waiting lists. Psychiatric nurses are now being trained to provide brief evidence-based interventions in primary care and also to provide important assessment and screening functions, so as to ensure that patients who need the services of the community mental health teams are suitably referred and those who can be managed at primary care level are provided with appropriate treatments. Nurses are now also 
increasingly involved in the delivery of computerized cognitive behaviour therapy, which, as a recent NICE review demonstrat-
ed,

ed,
(20) is effective in the treatment of a wide range of mental health 
problems. This method of treatment is particularly important given the scarcity of skilled therapist resources. Psychiatric nurses are therefore increasingly involved in the running of ‘Computer clinics’ , which now use a very wide variety of treatment packages for a whole range of disorders. Whist most of these packages come at a cost, there are now free to access programmes on the Internet. These include ‘Moodgym’ ,
(21) a programme for the self-help treat-
ment of depression, which is based on a cognitive behavioural approach and developed in Australia at the Australian National University in Canberra. Moodgym has been evaluated and its use is supported by positive randomized trial data.
(22)
Psychiatric nursing in the developing world

(22)
As noted above, there have been a number of training initiatives in the former communist countries of Eastern Europe and the former Soviet Union.
(1) Nevertheless, the numbers of trained psychiatric 
nurses across this region still remains fairly small. It is also clear that the skills of psychiatric nurses, in these countries, are compromised by the relatively poor general standards of mental health care.
With the exception of South Africa, psychiatric nursing is very 
poorly developed in the African continent. However, the World Health Organization has a number of projects that aim to integrate mental health into primary care provision. For example, the Ministry of Health in Kenya, the Kenyan Psychiatric Association, and the Kenyan Nursing Council are working with the UK Department for International Develo pment on a 5-year programme

1407
that began in 2005, which has the ambitious aim of training 
3000 primary care workers with some skills in very basic mental health care.
In Asia, psychiatric nursing is becoming increasingly recognized 
and there are now substantial training initiatives in the Indian subcontinent and China. Nevertheless, the numbers of psychiatric nurses who are needed in those vast countries are very great and, at present, the best way of describing the psychiatric nursing presence would be to say that it is sparse and patchy, with most nurses work-ing in the large cities. An additional problem is that, where reason-able standards of education and training exist (and this applies particularly to India and China) there is a considerable loss to immigration to the developed world—to countries such as the United Kingdom and the United States, where the recruitment and retention of psychiatric nurses is an ongoing problem, and is ﬁ  nan-
cially very attractive.

There is obviously enormous potential for the development of 
psychiatric nursing across the developing world and, although current initiatives have focused on providing nurses with basic skills, there is obviously enormous potential for the provision of evidence-based psychosocial interventions and, given the tremen-dous shortage of psychiatrists in many countries, nurse prescribing (providing that the nurses have received adequate education and training) could obviously potentially provide widespread beneﬁ  ts 
for a substantial proportion of the literally millions of people whose illnesses are currently untreated.

Psychiatric nursing is a relatively new profession, which has evolved over the past 50 years, from a branch of general nursing, where the main role focused on the custodial care of people with chronic serious and enduring mental illnesses—such as schizophrenia—to the present day situation, where nurses are, in the developing world at least, more likely to be university graduates who may be employed in a number of very diverse roles. The setting for these roles could be in inpatient settings, where custodial care is challenging, to say the least, to the community with roles involving psychosocial interventions within primary health care teams, to inpatient and community settings where nurses are increasingly autonomous prescribers of medication or psychological therapists. It is pleasing to note that the education and training of psychiatric nurses is gradually becoming more evidence based and policy makers are

apparently much more aware of the need to provide focused skill 
sets on populations of need.
From values to action: The Chief Nursing Ofﬁ  cer’s review of 
mental health nursing (2006)—England—http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4133839
American Psychiatric Nurses Association—http://www.apna.org/i4a/pages/
index.cfm?pageid=1
Newell, R. and Gournay, K. (2008). Mental health nursing: an evidence based 
approach  (2nd edn). Elsevier, London.
Australian and New Zealand College of Mental Health Nursing—http://
www.acmhn.org/index.htmlReferences
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projects/projects.asp
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report of the National Conﬁ  dential Inquiry into suicide and homicide 
by people with a mental illness . University of Manchester. 
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nursing for neurotic patients: a controlled trial. The British Journal of 
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 9. White, E. (1990). The third quinnenial survey of CPNs . Department of 
Nursing Studies, University of Manchester.
10. Gournay, K. and Brooking, J. (1994). The CPN in primary care: an 
outcome study. The British Journal of Psychiatry ,165, 231–8.
11. Gournay, K. and Brooking, J. (1995). The CPN in primary care: an 
economic analysis. Journal of Advanced Nursing ,22, 769–78.
12. Brooker, C., Fallon, I., Butterworth, A., et al.  (1994). The outcome 
of training community psychiatric nurses to deliver psychosocial intervention. The British Journal of Psychiatry ,165, 222–30.

13. Burns, T., Fiander, M., Kent, A., et al. (2000). Effects of caseload size on 
the process of care of patients with severe psychotic illness: report from 
the UK700 trial. The British Journal of Psychiatry ,177, 427–33.
14. Gray, R., Wykes, T., Edmonds, M., et al.  (2004). Effect of a medication 
management training package for users on clinical outcomes for patients with schizophrenia: cluster randomised controlled trial. The
British Journal of Psychiatry ,185, 157–82.
15. Gray, R., Leese, M., Bindman, J., et al. (2006). Adherence therapy 
for people with schizophrenia. The British Journal of Psychiatry ,
189, 508–14.
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17. Extended Nurse Prescribing. http://www.dh.gov.
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PublicationsPolicyAndGuidance/DH 4006775

18. Gournay, K. and Gray, R. (2001). Should mental health nurses prescribe? 
Maudsley discussion paper . Institute of Psychiatry, London.
19. Marks, I. (1985). Nurse therapists in primary care . RCN Publications, 
London.
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The clinical and cost effectiveness of computerised cognitive behaviour 
therapy for depression and anxiety. Technology Appraisal 51 . NICE, 
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21. Moodgym website: http://moodgym.anu.edu.au/
22. Christensen, H., Grifﬁ  ths, K.M., and Jorm, K. (2004). Delivering 
interventions for depression by using the internet: randomised 
controlled trial. British Medical Journal ,328, 265.6.4.2 psychiatric nursing techniques

SECTION 6  treatment methods in psychiatry 1408
6.4.3 Social work approaches 
to mental health work: international trends
The historical development of mental 
health social work
Social work was formally established in most European countries 
and North America at the end of the nineteenth century, before it took off gradually in other countries. It usually developed out of charitable work, which focused on ﬁ  nancial support for poor 
families. The second main strand in social work was represented by the Settlement Movement, which concentrated on improving the communal life of poor people by living with them, using com-munity work methods to support and empower.
The major impetus to developing mental health social work at 
the beginning of the twentieth century was related to the work of leading psychiatrists and psychologists with shell-shocked (PTSD) soldiers during the First World War.
(1) This approach lead to the

(1) This approach lead to the 
establishment of the psychodynamically oriented Tavistock Clinic in London, where the ﬁ  rst British psychiatric social worker was 
appointed in 1920.
(2) Stuart(3) argues that American mental health 
social work in the pre-1920 period concentrated more on care in the community in its social, rather than its administrative or psy-chological meaning, than after 1920, when it shifted further to the psychological dimension.
Social workers in both the children and the adults outpatient

Social workers in both the children and the adults outpatient 
services provided comprehensive psychosocial history of the child/adult and their family, enabled parents, teachers, and partners of adult clients to understand the underlying psychological reasons for the index client’s mental ill health, and guided them as to how they could actively support that family members.
(2) It was only in 
the 1950s that qualiﬁ  ed psychiatric social workers began to work in 
hospitals.
Since the 1970s all English-speaking countries have also opted 
for deinstitutionalization as their core mental health policy, leading to the closure of many of their psychiatric hospitals, replacing them by community-based services and by small psychiatric wards in general hospitals.
(4,5) With the notable exception of Italy,(6,7) most 
continental European countries have opted for bed reduction coupled with less extensive community services.
The trend towards deinstitutionalization is formally adhered

The trend towards deinstitutionalization is formally adhered 
to also in Latin America, but thus far is only practised in some small-scale projects.
(8,9) This applies also to Asia. MHSWs (mental 
health social workers) there focus mainly on sorting out beneﬁ  ts, 
though some are based in rehabilitation focused facilities where they work on connecting users to educational and employment opportunities.
(10)
This fundamental change has led to the relocation of MHSWs 
away from institutions into community services,(5) to a renewed 
interest in rehabilitation, and more recently also in the newly deﬁ ned recovery.
(11)
The paralleled development of private, for-proﬁ  t mental health 
services especially—but not exclusively—in the United States, has led to a further shift in the location of MHSWs and their work

services especially—but not exclusively—in the United States, has led to a further shift in the location of MHSWs and their work 
focus. Most United States MHSWs are to be found today working as psychotherapists in private practice or in managed care residen-tial units.
(12) In the latter they work with users who have long-term 
mental illness to a per capita budget.
Although the not-for-proﬁ  t sector has grown considerably with 
the focus on care in the community, MHSWs work there only in certain countries in which the public sector has either been reduced or never played the major part it does in the United Kingdom (e.g. the Netherlands, Hong Kong).
Underpinning values
Social work, including its mental health branch, is ethically governed by a set of values, which are expected to be universal and adhered to in everyday practice,
(13) even though its implementation may

(13) even though its implementation may 
prove at times to be problematic in terms of balancing care and control.
The values are derived from the liberal collectivist, humanistic, 
tradition of the twentieth century in which social work has developed.
The core values are social justice, respect for people who social 
workers meet at their most vulnerable state, readiness to help in a way which will enable the client to retain dignity, self-determination, and enhance their problem-solving abilities. Social workers are expected to take an active stance against any type of discrimination. Furthermore, social workers are committed to pursing a psychoso-cial approach in any type of their practice, and believe that most clients have the potential to grow and positively change.
Several elements stand out as central to MHSW:
1 The right to fail—this comes as part of the right to self-

determination, in that social workers are aware that risk needs to be taken at times to enable people to grow and develop, or as a basic human right of making a mistake. When social workers take this right seriously, they are able to have a genuine discus-
sion with clients as to the pros and cons of risk-taking, of 
learning from success as much as of learning from failure.
(14,15)
2 The wish to take an active stance against discrimination applies 
to working well with clients who come from ethnic minorities, from sexual orientation minorities, and to combating stigma against mental illness in one’s practice.
3 The adherence to a psychosocial approach entails ensuring that

3 The adherence to a psychosocial approach entails ensuring that 
both the psychological and the social aspects of users’ lives are attended to, an issue of importance in mental health where often biological aspects are attended to, but the psychosocial ones are not getting the same priority.
(16)
Conceptual developments
Psychodynamic approaches
As outlined above, mental health social work originated within the psychodynamic fold, though social workers did not practice psychoanalysis as a work method.
Social workers have tended to select from the range of psychody-
namic perspectives those theories, which were more focused on the ego, rather than on the id or the unconscious. The impact of ego psychology was/is in evidence in terms of understanding how people come to develop and maintain mental distress and mental

1409
illness, the importance of family dynamics, and of attachment to 
signiﬁ  cant others.(17, 18, 19, 20)
American social workers developed the crisis approach in its 
application to all areas of social work.(21) Based on Erickson’s 
notion of the normal crisis every person goes through when mov-
ing from one stage of life to another, major life events may lead initially to adverse reactions. However, with professional support people can reorganize their reactions more constructively, reduce the duration of these reactions, be more ready for change at the point of crisis, and learn how to improve their coping strategies and emotional responses. The problem-solving approach also originated from the United States, developed by Perlman.
(22)
Although the psychodynamic understanding of relationships is in 
evidence in her work, she focused on the process of social work with individuals and families (casework) and the client–worker relationships, beginning with the presenting problem.

The identiﬁ  cation of child abuse, especially child sexual abuse, 
and its implications for the mental health of children and adults in the 1970s and the 1980s led to refocusing on the psychodynamic approach among social workers in this area
(23) at a time in which 
all other approaches have paid less attention to the impact of such abuse on mental health.
Learning theory applications in social work
Behavioural social work
Behavioural social work developed in the United States in the 1950s, and is a leading approach in relation to people with milder forms of mental illness and problems of living.
(24) Its application 
within social work does not differ in any signiﬁ  cant way from its

within social work does not differ in any signiﬁ  cant way from its 
application within psychiatry or psychology. In this sense it is not a social work approach. A number of inﬂ  uential texts appeared in 
the United Kingdom which demonstrated the research evidence pertaining to the effectiveness of the approach in a number of social work areas.
(25)
Task-centred social work
This orientation takes further the crisis perspective and the lessons from learning theories and behaviour modiﬁ  cation.
Reid and Epstein
(26, 27) , as well as Marsh and Doel,(28) proposed 
that people work better on their problems if focused on speciﬁ  c 
targets and if the problem-solving effort leads to success, however small. Research evidence demonstrated the usefulness of this approach to different aspects of social work, such as direct work with children and their parents, as well as with people suffering from mild mental distress symptoms.

The social dimension in mental health social work
Social workers and theorists interested in the social dimension began usually from the assumption that inequality in opportuni-ties and in civic participation due to poverty may increase the rate of mental illness among poor people. This assumption follows Merton’s classical matrix of the reactions to the gap between social goals and means, in which mental illness is a reaction of people who accept socially desirable goals, but withdraw from obtaining them after being frustrated in doing so, whilst at the same time not adopting antisocial means (as in criminal behaviour) or develop-ing an alternative model of society (social rebels).This strand of thinking was reinforced in the 1960s and 1970s by 
the application of Marxist thinking and the combined impact of the deviancy and anti-psychiatry orientations.
(29) Discrimination 
on the basis of age, ethnicity, gender, or sexual orientation

on the basis of age, ethnicity, gender, or sexual orientation 
was added in the 1980s to the likely social factors which foster inequality.
Social workers accepted the logic presented by sociologists such 
as Goffman and Scheff 
(30, 31, 32) that the stigma attached to mental 
illness is largely irreversible, as it is accepted both by others and by the individual concerned who in turn internalizes his or her poor social status.
Interestingly, although accepting the enormity of the labelling 
process, social workers did not count themselves among the labellers.
The appeal of the anti-psychiatry approach for social workers 
related to acknowledging the price of labelling for the individual concerned, and the considerable shortcomings of a system focused on the psychiatric hospital and medication in which psychological and social factors were largely ignored.

T oday the social perspective implies a greater focus on social 
inclusion, supporting users and carers-led initiatives, ensuring ﬁ nancial support side-by-side with the critique of the medical-
ized approach to mental health and illness, of modernity and post-
modernity.
(16)
A more recent strand of this approach is outlined in the critical 
social work, which applies a post-modern perspective to the analysis of where social work is, as well as the issues and dilemmas related to mental health social work. Bainbridge
(33) highlights the 
need to focus on the social dimension and sociological understand-ing of mental ill health in social work, as well as on issues of power and empowerment.
(a)  The social role valourization (SRV) and the 
strength approach
This approach was initially developed by psychologists in the ﬁ  eld 
of learning difﬁ  culties.(34–37)
SRV accepts the deviancy approach up to the point at which the

SRV accepts the deviancy approach up to the point at which the 
impact of labelling and segregation is said to be irreversible. Conversely, SRV is focused on reversing the devaluation of the dis-abled person and the group, while accepting that a disability exists. The devalued existence can be reversed by the combined impact of the following:
◆ enabling those who have been segregated to live in the commu-
nity by providing them with the opportunities to do so and the support they require for this purpose
◆ enhancing the competencies of the disabled person
◆ changing their public image, in part by their positive presence in 
ordinary settings in the community
◆ upgrading the state of the physical settings in which a disabled 
group is treated, lives, and works
◆ changing the derogatory language used in both professional and

◆ changing the derogatory language used in both professional and 
lay circles in describing people with disabilities.
Its protagonists are critical of professional attitudes, knowledge, 
and skills, including those of social workers (see Wolfensberger).(35)
Y et as a group social workers have within their repertoire more of the attitudes, knowledge, and skills required by this approach than any other mental health profession. Furthermore, SRV offers an 6.4.3 social work approaches to mental health work: international trends

SECTION 6  treatment methods in psychiatry 1410
interesting and comprehensive combination of psychological and 
social dimensions; for an application to how it can work with the Nearest Relative in mental health.
(38)
In the United States and Canada, but much less so in the United 
Kingdom, SRV came into prominence within social work through 
the strengths  model of social work.(39) The model is unique in 
concentrating on the strengths the person and his or her environ-ment possess, and how these could be harnessed to solve the speciﬁ  c 
problem and lead to an improvement in the person’s quality of life. Coming together with a focus on following people’s ambitions (as long as these are within socially acceptable norms), this orientation has led to useful and positive outcomes in care management.
(40)
A further development of the strengths model is the growing interest in focusing on enhancing resilience in mental health social work.
(41)

(40)
(41)
Interestingly, the approach has been adopted by other mental 
health professionals in the ﬁ  eld of employment without acknowl-
edging the debt to social work.
Legally anchored MHSW
The social mandate of social work is anchored within legal and policy frameworks; this applies to MHSW too.
Securing beneﬁ  ts
In all countries social workers are gatekeepers to and advocates for 
securing beneﬁ  ts either in cash (e.g. disability allowance, Direct

securing beneﬁ  ts either in cash (e.g. disability allowance, Direct 
Payment agreement) or in kind (e.g. housing, clothing). They often have to make the claim in addition to the client, verify the claim as against eligibility criteria, secure supporting documents from other professionals, at times negotiate with other agencies (e.g. social security, health, education), and in a number of countries they are indeed located in social security services (e.g. Portugal, Israel).
While this work is considered to be routine, its importance in the 
life of poor people cannot be underestimated. The evidence high-lights that most people with enduring mental illness are poor,
(42)
and that remaining poor is a strong counter-indication to becom-ing mentally healthy. Furthermore, the evidence related to Direct Payment in mental health,
(43) which enables users to take the

(42)
(43) which enables users to take the 
driving seat as to how they spend their budget in agreement with the local authority and mental health trust, illustrates the social inclusion and recovery value of such a scheme which clearly comes out of the strengths model.
Knowledge of the available resources and eligibility is needed for 
this type of work, as well as the ability to inform users and enable them to participate as deserving partners.
In a large number of countries this is the main social work task 
in mental health (e.g. Brazil, Greece, Italy, Ireland, Portugal, and Poland).
The approved social worker
This role illustrates an enhanced legal position for MHSWs; its fullest form is practised in the United Kingdom.
The approved social worker was developed in Britain to provide

The approved social worker was developed in Britain to provide 
a complementary measure to the psychiatric perspective within the 1982 amendments to the 1959 Mental Health Act.
Social workers were seen as suitable professional ﬁ  gures who 
would represent the psychosocial angle in parallel to the psychiatric view in the following instances:◆ assessing people when an application has been made for a 
compulsory admission to a psychiatric unit
◆ the follow-up to such an admission
◆ mental health review tribunals (established within the 1959 
Mental Health Act)
◆ work with the Nearest Relative(38)
◆ coordinate the multi-disciplinary assessment, which needs to be 
carried out by a psychiatrist and a GP in addition to the social worker. This assessment has to be carried out within a speciﬁ  ed 
limited period of time.
Each of these tasks calls for somewhat different knowledge

Each of these tasks calls for somewhat different knowledge 
and skills, as well as emphasis and use of a range of more generic skills.
(44) In each task social workers are asked not to replicate the 
psychiatric assessment but to compliment it. For example, they have to look for the least restrictive alternative to the hospitaliza-tion before they can recommend a hospital admission, rather than diagnose mental illness. Social workers have an autonomous position as they can disagree with the views of the other professions. The role requires exercising more social control than care, a con-tested issue within social work.
Training to become an approved social worker requires 60 days 
of academic input and supervised practice initially, followed by 5 days refresher training annually. Individual social workers can take it up after 2 years of post-qualiﬁ  cation work experience.

of academic input and supervised practice initially, followed by 5 days refresher training annually. Individual social workers can take it up after 2 years of post-qualiﬁ  cation work experience. 
This compares with 2 days training for general practitioners and 1 day for psychiatrists.
Most of the activities undertaken by MHSWs with adults since 
1983 are related to meeting the requirements of this role. Existing 
evidence
(45) highlights that in most cases ASWs are working to a 
good standard. The role also offered MHSW a higher status and pay, but came with the price tag of giving up most of their previous activities, such as family work, group and community work, and work with users who have minor mental illness. However, the pro-posed new English Mental Health Act
(46) includes the introduction

(46) includes the introduction 
of AMHPs (Approved Mental Health Practitioners) who can come from any mental health discipline, but likely to be nursing because of the numerical dominance of nurses in the English mental health service. ASWs are unhappy at being dethroned of their unique legal role, arguing that nurses do not have the same background training for psychosocial understanding and intervention.
Workforce research into ASWs
(47) has highlighted a recent steady 
decrease in the number of ASWs, a high number of workers approaching retirement age and low morale, factors likely to have played a part in the government’s wish to introduce other profes-sions to this role. There are currently 4500 ASWs, a minority in the total workforce of social workers in England which stands at 46 000.
While current ASWs and MHSWs will be able to be part of the 
AMHP workforce, this change may also enable them to reclaim some of their previous roles and activities.
Care management

In all English-speaking countries and a number of European countries (e.g. the Netherlands, Slovenia), MHSWs are also often engaged in one form or another of care management, which follow the speciﬁ  c laws and regulations of each country (e.g. the Care in 
the Community 1990 Act in England).

1411
Care management (not be confused with managed care) is a 
form of coordinating the assessment, planning, and interventions with people who require long-term care, including in mental health. It is aimed at preventing fragmentation and duplication of professional input and services, as well as ensuring that services follow the user’s needs, and not vice versa as was—and still is—the case all too often. While in the United Kingdom, psychiatrists are formally the nominated care manager since 1995, and CPNs are the professionals in more frequent contact with the users, in other countries such as Australia, New Zealand, and Canada, social workers are often the nominated care coordinator.
Care management can be practised in a variety of ways, ranging 
from a purely administrative orientation, through clinical care management, to one anchored within the strengths and recovery orientations.
(40, 48, 49) The choice is often dictated by the managers

(40, 48, 49) The choice is often dictated by the managers 
of a local authority or a mental health trust.
Community treatment orders (CTOs)
CTOs constitute a third legally deﬁ  ned area in which MHSWs are 
engaged. They originated in the United States, and exist in a variety of formats in Canada, Australia, and the United Kingdom.
(50–52)
They represent a response to the escalation of concerns about risk avoidance in the ﬁ  eld of mental health, closely related to the growing 
fears of risk raised by modernity and post-modernity,
(54, 55)  and 
reinforced more recently by fears of terrorism as a particularly threatening type of risk. It is indicative that this preoccupation is not shared between North and South Europe; it is much more prominent in the North.
Following a legal process, CTOs enable the nominated mental

Following a legal process, CTOs enable the nominated mental 
health professional to require a service user to adhere to speciﬁ  c 
restrictions, such as to live in a certain facility or to present them-selves for interventions at speciﬁ  c locations. This measure has been 
introduced to ensure that users with long-term mental illness who lead a disorganized life (e.g. often do not comply with medication, live rough, misuse substances, mishandle money, misagreed appointments, and get into trouble with the law) will have a safety net, which structures their lives. There is some evidence of the 
effectiveness of CTOs,
(48, 49) but it seems restricted to speciﬁ  c 
subgroups within the broader category of people with severe and enduring mental illness.
Social workers are often the nominated professionals responsi-
ble for the agreed plan and enforcement of the CTO. This puts them in a somewhat conﬂ  ictual position regarding the desired

ble for the agreed plan and enforcement of the CTO. This puts them in a somewhat conﬂ  ictual position regarding the desired 
focus on care in social work, as it is tilted more towards the control element.
(56)
Non-legally anchored MHSW
The constraints on this type of work come not only from the primacy of legally sanctioned work, but also from working within welfare bureaucracies, for a private employer interested primarily in proﬁ  t, or for an impoverished not-for-proﬁ  t service.
Despite these constraints, we have examples of good and innova-
tive MHSW practice in most countries, which include:
◆ Successful attachment to primary care was established as early as

◆ Successful attachment to primary care was established as early as 
1965 in London, with the social workers, their clients, and the general practitioners expressing satisfaction with this way of working. Nevertheless, this form was largely abandoned owing to the focus on statutory responsibilities.◆ Social workers pioneered collective user involvement approach 
during the early 1980s(57) some years before it became fashion-
able in wider circles.
◆ Applying self-directed group and community work approach to 
working with mothers of abused children, empowering them to take control over their lives.
(58)
◆ Initiating de-institutionalization in social care institutions in 
Slovenia.(59)
◆ Creating family support teams(60) where most staff members are

(58)
◆ Creating family support teams(60) where most staff members are 
social workers providing brief assessment and consultation to families of children with minor mental distress, and are often successful in preventing the need for referral to more expensive services.
◆ Establishing the Building Bridges project in which parents with 
mental health difficulties and their children are supported together as well as separately.
(61)
◆ Creating The Faith Links project, a multi-faith project within an 
inpatient service in which users, volunteers, and social workers plan joint activities which follow users’ spiritual wishes.
(62)
◆ Supported education and employment schemes in mental health 
initiated by social workers.(63)

(62)
Mental health social work is a broad, rather than a rigorous, church. Since the 1980s social workers have gained in professional status by the introduction of the roles of the approved social worker (or licensed to carry out civil commitment in the American context), care co-ordinators, managers of managed care facilities, or psycho-therapists. These gains have come at a price outlined in the text above.
Often the cost of closer collaboration within the multi-disciplinary 
framework has led to the risk of giving up the attempt to hold on to, and further develop, an alternative and complimentary perspec-tive from that of psychiatrists, nurses, or psychologists, as well as raising doubts as to the uniqueness of MHSW.
The increased narrowness of the role is not simply the byproduct 
of the legal framework. It is also due to increased specialization

of the legal framework. It is also due to increased specialization 
within mental health on the one hand, and the effects of neo-
liberal policies globally on public sector funding on the other hand.
The move to privately contracted work, either in managed care 
or in psychotherapy so apparent in the United States, is yet another outcome of neo-liberal policies which fragments MHSW. As a trend we are likely to see growing beyond the United States, the increased concentration of mental health social workers within the private sector does not bode well for a profession whose value base focuses on the need to protect the more vulnerable and stigmatized populations, and to provide the dual perspectives of psychosocial input.
Mainly due to governmental pressure related to fear of risk and

Mainly due to governmental pressure related to fear of risk and 
its potential political fallout, the focus on working exclusively with people experiencing long-term severe mental illness has contrib-uted to the increasing narrowness of the role of social workers in most First World countries. The paralleled withdrawal of social work involvement with people who have milder forms of mental distress within public sector and not-for-proﬁ  t services, and its 6.4.3 social work approaches to mental health work: international trends

SECTION 6  treatment methods in psychiatry 1412
increased availability only to those who can afford it, is a reﬂ  ection 
of this situation.
The core qualities of belief, optimism, and caring of MHSWs 
identiﬁ  ed in a cross-national research(64) coupled with the ability 
of MHSW to innovate as highlighted in this chapter, illustrate the 
optimistic scenario for positive change within this branch of social work. However, unless theory building and research aspects are given the importance they deserve within MHSW globally, includ-ing an inevitable critical dimension of the existing system, mental health social work is likely to be no more than a reﬂ  ection of the 
developments in other professions. This will not only mean curtail-ing its autonomous potential, but also the impoverishment of the multi-disciplinary framework as a whole of a crucial dimension necessary for its comprehensive work, as exempliﬁ  ed in some recent 
work on the social aspects of MHSW.
(16)

(16)
In addition, mental health social work will have to develop a 
much stronger policy making function, if it is to provide a more responsive, effective, and comprehensive service to users, relatives, and the communities in which these people live.
Norman, E. (ed.) (2000). Resiliency enhancement: putting the strength 
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the promise of the psychosocial approach . Ashgate Publishing, 
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6.4.4 Art therapy
The fundamental principles of art

The fundamental principles of art 
therapy/art psychotherapy
Descriptions of art therapy from two of the oldest and largest 
professional associations, the British Association of Art Therapists and the American Art Therapy Association refer to: the use of art materials for self-expression and reﬂ  ection in the presence of a 
trained art therapist. Art therapy uses the ﬂ  exible, creative problem-
solving potential of art-making to improve and enhance the physical, mental, and emotional well-being of individuals of all ages. The relationship between the therapist, client, and their artwork is of central importance. Art therapy can be used on a one-to-one and group basis.
Art therapy (or art psychotherapy, both titles are protected 
by law) in the United Kingdom is ﬁ  rmly rooted in psychodynamic

by law) in the United Kingdom is ﬁ  rmly rooted in psychodynamic 
and humanistic concepts and practices appropriate to public sector settings, and adapted to the social and mental health of the client. 
It is a broad-based discipline, involving substantial knowledge of 
the visual arts, individual and group psychotherapy, social and communication sciences, and the impact of culture on health.
(1)
Main premises
◆ That visual image-making is an important aspect of the human 
learning process;
◆ That art made in the presence of an art therapist may enable a 
person to get in touch with feelings that cannot easily be expressed in words;
◆ That the creative process helps people to resolve conﬂ  icts and 
problems;
◆ That art can act as a ‘container’ for powerful emotions and be a 
means of communication between client(s) and therapist;
◆ That the image can serve to illuminate the transference in the

problems;
◆ That the image can serve to illuminate the transference in the 
case of a psychodynamic approach.
Engagement in image-making is of central importance although 
clients do not need any prior experience of or skill in art, as the aim is not to produce a ‘good’ piece of art that can be exhibited. The images made in art therapy may embody thoughts and feelings, be a bridge between the ‘inner world’ and outer reality, be a mediator between unconscious and conscious, hold and symbolize past, present, and future aspects of a client’s life. Ambivalence and conﬂ  ict 
can be stated and contained within an image. In art therapy the client tries to give form to what seem to be inexpressible or unspeak-able feelings, which they can then share with the art therapist.6.4.4 art therapy

SECTION 6  treatment methods in psychiatry 1414
The focus of the transference (bringing feelings from the past into 
the present), can be onto the art object rather than to the therapist directly, adding a ‘third dimension’ to the therapeutic process.
(2–4)
An important aim, as with all psychotherapy, is to bring about 
change. Positive change may occur when a client can direct their 
strong feelings into making art and when the therapist helps the client to tell their story through the art. How, when, and if change occurs obviously depends on their capacity to engage with this process and needs much time and patience while the client builds conﬁ  dence. For verbally inarticulate clients, or those who use words 
defensively, engagement with the art materials gives the opportu-nity to understand self and environment, communicate emotions to the therapist, receive feedback, and encouragement.
The historical development of art therapy 
in the United Kingdom, United States, and Europe

There are parallels in the development of art therapy in the United 
Kingdom and United States, early history being shared with that of group analytic psychotherapy as a phenomenon of the Second World War rehabilitation movement.
(5–7) In the 1940s and 1950s 
art therapists were simply artists working in hospitals who empha-sized the healing role of art. In 1963, the British Association of Art Therapists was formed from this small group of artists and art educators, who set themselves the task of deﬁ  ning and extending 
the activity, preparing standards for training in the higher educa-tion sector, informing the public and other professionals of the potential of art therapy, and working towards a career and salary structure in the National Health Service (NHS). The ﬁ  rst postgrad-
uate trainings  began in the late 1960s. The positive response of

uate trainings  began in the late 1960s. The positive response of 
the NHS and other organizations to art therapy’s beneﬁ  cial impact 
led to a petition being made for statutory regulation under the old Council for Professions Supplementary to Medicine in 1991, approved in 1997, after which art therapists, along with music and dramatherapists had their own federal Board at the Council. They 
were transferred to the Health Professions Council in 2001. Training

were transferred to the Health Professions Council in 2001. Training 
in the United Kingdom is now at Master’s level, in four universities in England, one in Scotland, one in Northern Ireland, and usually follows a degree in art and design. Study of psychotherapeutic principles, visual art, and practical placement are important elements in the training. Elsewhere in Europe the picture is very different with some countries sharing the UK standards, others having no training or a great variety of trainings in both the public and private sector. The United States, Australia, and New Zealand have the same requirements of a Master’s level qualiﬁ  cation in 
order to practice. (See website references for more information.)
The development of art therapy with 
speciﬁ  c client groups
One of art therapy’s main advantages as a treatment is its ﬂ  exibility. 
It can be used with many different client groups and some of these are discussed as follows:
Children

Children
Many founder art therapists in the United Kingdom and United States were art teachers and were inﬂ  uenced by the ‘child-centred’ approach to art education that developed in the 1930s. American 
pioneer Kramer considered that it was art activity itself that had inherent healing properties; and that within a secure relationship with the therapist, a child could sublimate their destructive and aggressive feelings by producing an object, which would symbolize those feelings, prevent them being acted out and lead to more insight and control. This often led to change in behaviour.
(8)
Others pioneers from the United States gave examples of how

(8)
Others pioneers from the United States gave examples of how 
group work could enable angry and shameful feelings to be shared among the group members as well as the therapist, to the relief of the child as well as his peers.
(9) Many art therapists specializing in 
work with children attest to the importance of play and to the role of art materials in allowing regression in the form of mess-making. This seems to be particularly beneﬁ  cial for children who have 
suffered sexual abuse
(10–12) due to the loosening of control that 
happens when a child becomes deeply immersed in the physical process of painting and is able to lower defences as a result. Materials may be smeared, spilled, and wasted and it is important that the therapist maintains control of the boundaries and is able to tolerate a high level of anxiety as the child attacks the therapeu-tic space.
(13)
Art therapy is helpful for children suffering from chronic

(13)
Art therapy is helpful for children suffering from chronic 
constipation, faecal overﬂ  ow soiling, and also ‘antisocial behaviour’ 
and Aldridge(14) pointed out the relationship she observed 
between food, painting, and faeces while working with neglected and abused children in the context of a social services Unit and how mess-making was important in their creative development. Ambridge
(15) discussed how images may be used to reﬂ  ect mother–
child relationships with children who have been sexually abused and are often so traumatized that they cannot speak about their experiences.
The physical involvement in the art materials in enabling 
regression and essentially in receiving containment and acceptance from the therapist is very important to all the children mentioned above.
Dubowski
(16,17)  used a Developmental Art Therapy approach in 
research with children with learning difﬁ  culties, aiming to help the

Dubowski
research with children with learning difﬁ  culties, aiming to help the 
child to achieve his or her maximum potential. Understanding creativity and mark-making in early childhood is as important in this model as understanding psychodynamics. Studies made by Kellog
(18) of over 100 000 children’s scribbles inform our under-
standing of the developmental process leading to production of meaningful marks. Visual problem-solving through picture-making is developed between the age of about 18 months (when hand-eye co-ordination has developed to the extent that they can grasp an implement and direct it to a picture surface while attend-ing to the activity) and 4 years, by which time most have developed the capacity to make recognizable pictures endowed with symbolic meaning.
(19) This model draws on insights from art educationists, 
most recently Matthews.(20,21)  Art therapists have also contributed

most recently Matthews.(20,21)  Art therapists have also contributed 
to the emotional and educational development of children with Autism.
(22,23)
Art therapists also occasionally work with families and this is an 
emerging area of interest.
People with learning difﬁ  culties
Stott and Males(24) were among the ﬁ  rst British art therapists to 
write about their work in a large hospital with people who had

1415
lived in institutions most of their lives. They suggested that art 
therapy offered a means of communication and of self-expression through which difﬁ  culties of life in an institution, such as loss of 
identity, could be eased. Their goals were: to ﬁ  nd the art medium of 
most use to each resident, bearing in mind any physical handicaps; to set-up the art therapy sessions at regular times and in the same place; record and report the results of sessions; to enable maximum communication to take place. For some long-term residents, the art therapy studio became an ‘oasis’ in the desert of the hospital and they gained an identity as ‘artist’ .
Their work was continued by a generation of art therapists 
concerned about the effects of institutionalization on long-stay residents. Drawing on Gardner’s work concerning the categories of personal and spatial intelligence
(25) Rees set-up a qualitative

(25) Rees set-up a qualitative 
research project using a detailed observational schedule with a group of women with severe learning difﬁ  culties in a single-sex 
locked ward, conducted over 3 years to investigate clients’ use of physical space and its potential symbolic signiﬁ  cance. Rees found that by relating to physical and spatial aspects of their envi-ronment, some clients discovered an effective way of maintaining some level of psychological and emotional integration. They were helped to manage their often overwhelming feelings and to develop a stronger identity in their, albeit, very restricted environment.
(26)
Strand used a group interactive art therapy model with a group of learning disabled clients whom she observed to be suffering from loss and despair as a result of their emotional needs being neglected.

(27)
Now that people with learning difﬁ  culties mainly live in the 
community, art therapists are now able to assist clients in develop-ing resources to manage their day-to-day activities, and to improve their quality of living—particularly social interaction—through engagement in creative activity, often in groups. Insights from earlier work on institutionalization and exclusion now inform art therapy with older residents in care homes.
Offenders
Liebmann used art therapy within probation services to address ‘offending behaviour’ directly
(28) summarizing the beneﬁ  ts to 
offenders as follows: as a means of non-verbal communication, important for the high percentage of offenders who have poor verbal skills, conversely with those who use words defensively; to release angry and aggressive as well as shameful and embarrassed feelings and provide an acceptable way of looking at and dealing with difﬁ  cult emotions; client and therapist together could look

back at the images over a series of sessions, see patterns and note developments; active participation is required, helping to mobilize those who may not be voluntary clients and bring about favourable behavioural changes that outlast the session itself. Liebmann devised strategies to help offenders gain insight into their behav-iour, for example, the comic strip where the client is asked to draw an important life event within frames, the sequences of which 
can then be discussed and alternative options suggested.
(29) This 
approach combines some elements of cognitive behavioural therapy with a psychodynamic approach, providing a structure, which is empathetic but on the other hand does not collude with offending behaviour, nor accept it as inevitable.
T easdale produced a set of Guidelines while working in the pris-

on service. These focus on inmates and on the prison environment, reinforce many of the points above, such as using art therapy to support prisoners in coping with their imprisonment, address feel-
ings of separation, isolation, loss, low self-esteem. Speciﬁ  c advice is 
offered for conducting art therapy within a prison context.
(30)
People with psychotic illness
From the 1940s art therapists have worked with long-stay clients in psychiatric hospitals modifying the effects of institutionalization through detailed attention to communication when even the most psychotic patients could communicate through images and have this acknowledged. Now that people with psychosis increasingly live in the community and cope with the challenges of everyday life the focus is on issues of independence, isolation, building relation-ships, managing the illness, and its impact on self and family.
(31)

(31)
Work with acutely psychotic clients, on the other hand, takes 
place on wards, is normally brief and aimed at helping the client to interact positively with others usually in ‘open’ studio groups with a rapidly changing population, or for those in a serious acute state, on a one-to-one basis. Drawing on process-oriented psychology McClelland
(32) has devised a new model using art therapy to work 
directly on the acute state itself, requiring an active and assertive therapist style and meeting the client in their own ‘language’ however bizarre this may seem.
Older people
With older people’s mental health and well-being coming under increased government scrutiny, this is an area where art therapy has much potential to be beneﬁ  cial. Art therapists in this ﬁ  eld have

noted that attention to loss, fear of illness and dying, feelings of helplessness and dependency is necessary in alleviating depression. Recent art therapy research with older people with dementia showed some improvements in mental acuity, calmness, sociability, and physical competence following 40 weekly sessions of group work, compared to no change in the control.
(33)
As with other client groups, engaging in creative activity can 
also provide an outlet for frustrations to do with ageing, as well as possibly leading to a challenging and rewarding hobby.
Art therapy is used with people suffering from cancer, including terminal cancer
(34,35)  as well as with other long-term and progres-

sive illnesses or conditions such as multiple sclerosis, ME, kidney disease, effects of stroke, Parkinson’s disease, and in palliative care to manage anxiety and fear about death and dying. The aims are to assist clients in coping with the emotional impact of their illness, enabling expression of feeling, relieving depression and stress, and improving their quality of living.
Other areas  where promising work is going on: with eating 
disorders, drug and alcohol addiction, and with refugees and asylum seekers, many of whom have been the victims of war, of torture and are suffering extreme stress; also with the moderately to severely depressed and those who have work and relationship difﬁ culties.
Contextual issues
In the United Kingdom, over 50 per cent of art therapists work

In the United Kingdom, over 50 per cent of art therapists work 
within the NHS where they may form part of the psychological therapies or occupational therapy department, or be autonomous. Others practise in Social Services, Education, Home Office, 6.4.4 art therapy

SECTION 6  treatment methods in psychiatry 1416
non-Statutory services, and a fairly small percentage work privately 
or are self-employed.
All are capable of assessing the suitability of the client for art 
therapy. Exclusion criteria are minimal. Initial interviews usually explain that the client does not have to be ‘good at art’ and that art therapy is not a ‘painting class’ but that it may arouse strong and sometimes difﬁ  cult feelings. All therapists are trained to work with 
individuals and groups, to function as members of multi-disciplinary teams, to manage health and safety issues concerning preparation and maintenance of the art therapy space, liaising regularly with medical, nursing, teaching, or other appropriate staff in the interests of the client. Ethical standards are laid down by the Health Professions Council as for the other arts therapists (drama and music and also dance) with whom there is regular contact.
Research

Research
There is a substantial body of qualitative research in art therapy, however much of this would not meet the criteria for evidence-based practice required by today’s public sector. Currently there is very little about art therapy within National Institute of Clinical Excellence guidelines, which have tended to emphasize quantitative studies. This is unfortunate as it gives the impression of a profession without a strong evidence base, which is not so as the ﬂ  ourishing 
Art Therapy Practice Research Network and a growing body of literature demonstrates.
(36, 37)
A few books and papers emerging from control group studies 
feature evaluations of art therapy groups with older people with moderate to severe dementia
(38) and with schizophrenia. In 2006,

(38) and with schizophrenia. In 2006, 
the UK Health T echnology Assessment supported a consortium headed by Crawford, Killaspy, and Waller (University of London) for a multi-centre random control group study of art therapy and schizophrenia. The Master’s level training in art therapy requires a substantial dissertation, and a signiﬁ  cant percentage of art therapists
continue to doctorate research designed to use and test the hypoth-eses emerging from over 60 years of detailed casework.
British Association of Art Therapists: www.baat.org.
Health Professions Council: www.hpc-uk.org (Art, Drama and Music 
Therapy).
International Society for the Study of the Psychopathology of Expression 
and Art Therapy: http//www.online-art-therapy.com/
American Association of Art Therapists: www.arttherapy.org.

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enriching communication: art therapy for children with autism. In Development and diversity: new applications in art therapy  (ed. D. 
Sandle), pp. 57–77. Free Association Books, London and New Y ork.
23. Tipple, R. (2003). The interpretation of children’s art work in a 
paediatric disability setting. Inscape ,8, 48–59.

24. Stott, J. and Males, B. (1984). Art therapy for people who are mentally 
handicapped. In Art as therapy  (ed. T. Dalley), pp. 111–26. Tavistock, 
London.
25. Gardner, H. (1984). Frames of mind: the theory of multiple intelligences .
Paladin, London.
26. Rees, M. (1995). Making sense of marking space: researching art 
therapy with people who have severe learning difﬁ  culties. In Art and 
music therapy and research  (eds. A. Gilroy and C. Lee), pp. 117–37. 
Routledge, London and New Y ork.
27. Strand, S. (1990). Counteracting isolation: group art therapy for people 
with learning difﬁ  culties. Group Analysis ,23, 255–63.
28. Liebmann, M. (ed.) (1994). Art therapy with offenders . Jessica Kingsley, 
London.
29. Liebmann, M. (1998). Art therapy with offenders on probation. In

London.
29. Liebmann, M. (1998). Art therapy with offenders on probation. In 
Development and diversity: new applications in art therapy  (ed. D. Sandle), 
pp. 104–20. Free Association Book, London.
30. T easdale, C. (2002). Guidelines for arts therapists working in prisons .
Department for Education and Skills/HM Prison Service, Prisoners’ Learning and Skills Unit.
31. Killick, K. and Schaverien, J. (1997). Art psychotherapy and psychosis .

1417
32. McClelland, S. (1992). Brief art therapy in acute stages: a process-
oriented approach. In Art therapy: a handbook  (eds. D. Waller and 
A. Gilroy), pp. 189–208. Open University Press, Buckingham.
33. Rusted, J., Sheppard, L., and Waller, D. (2006). A multi-centre 
randomized control group trial on the use of art therapy for older 
people with dementia. Group Analysis ,39, 517–36.
34. Pratt, M. and Wood, M. (eds.) (1998). Art therapy in palliative care .
Routledge, London and New Y ork.35. Waller, D. and Sibbett, C. (eds.) (2005). Art therapy and cancer care .
McGraw-Hill, Maidenhead.
36. Karkou, V . and Sanderson, P . (2006). Arts therapies: a research based 
map of the ﬁ  eld. Elsever, London.
37. Gilroy, A. (2006). Art therapy ,research and evidence based practice . Sage, 
London.
38. Waller, D. (ed.) (2002). Arts therapies and progressive illness .
Brunner-Routledge, Hove and New Y ork.6.4.4 art therapy

6.5
Indigenous, folk 
healing practices
What are indigenous, folk healing practices?
Indigenous, folk healing practices are nonorthodox therapeutic 
practices based on indigenous cultural traditions, operating out-side of ofﬁ  cial (modern) healthcare systems.
(1) These practices are 
often validated by experience, but are not founded on scientiﬁ  c 
principles. Indigenous healing practices are observed in ‘primitive’ or ‘pre-industrialized’ societies as well as in modern or developed societies. All healing practices or psychotherapies are more or less culturally inﬂ  uenced, including modern and orthodox psychother-
apies, but indigenous healing practices are described as ‘culturally embedded’ because they are often intensely embedded in the cul-tural systems in which they were invented and in which they are practised. They are, therefore, usually very difﬁ  cult to transplant to

entirely different cultural settings, where they do not have the same meaning or legitimacy.
(2)
While indigenous healing practices function in general as heal-
ing methods for problems, they are not usually considered by either 
the healer or the clients to be psychological therapy for the clients’ 
emotional or psychological problems. Rather, they are recognized as religious ceremonies or healing exercises related to supernatural or natural powers. However, from a mental health point of view, the indigenous healing practices often provide psychotherapeutic effects for the clients, and can be considered as folk psychotherapy.
Anthropologists have studied folk healing practices as a part of

Anthropologists have studied folk healing practices as a part of 
cultural behaviour. Recently, cultural psychiatrists have become interested in examining indigenous healing practices from clinical perspectives to explore the similarities and differences that exist between folk healing practices and modern psychotherapy, and to disclose the therapeutic mechanisms that are operating in and being utilized by indigenous healing practices. Many people in developed societies utilize folk healing practices as adjunctive to their primary (modern) therapy or as their main way to get help. Therefore, it is relevant for the modern psychiatrists to know what 
they are and the possible therapeutic mechanism they offer, or the 
possible negative effects they may receive by utilizing such indige nous
healing practices.
Various practices are covered by the loosely deﬁ  ned terms,

Various practices are covered by the loosely deﬁ  ned terms, 
indigenous or folk healing. Religious healing practices and ceremo-nies are closely related to a speciﬁ  c religion. Shamanism involves 
a spirit medium. Divination, or various kinds of fortune-telling, including astrology or physiognomy, may be used by people to 
solve their psychological problems or to seek answers for life prob-lems, and, therefore, can be viewed as folk counselling practices as well. Furthermore, the practice of meditation, a self-training exercise 
used to obtain tranquility, growth of mind, and prevention of emotional problems, can be considered a folk healing practice if one deﬁ  nes psychotherapy very broadly, as not only treating a suf-
fering person but also providing a means for preventing problems and improving the quality of a person’s mental life.
(3)

(3)
No matter what terms are used, indigenous healing practices 
share some common features. They are invented and utilized by local people for the purpose of solving problems or treating suffering—therefore, they are called indigenous in contrast to uni-versal. They are distinctly different from the modern (Western or 
orthodox) professional medical approaches—thus, they are called folk practices. Most of them are supernaturally oriented and remote from any scientiﬁ  c orientation. Such indigenous practices are 
usually rooted in traditional beliefs and folk interpretations of problems, and, thus, are closely related to cultural beliefs.
Subdivision of various healing practices

Based on their core nature and their basic therapeutic orientation, healing practices observed in different societies can be subdivided into different categories namely, supernatural orientation (such as spirit mediumship, religious healing ceremony, and divination); nature orientation (such as fortune-telling, astrology, and medita-tion); medical-physiological orientation (such as mesmerism, acupuncture, and herb medicine); and socio-psychological 
orientation (such as Zen training, Alcoholics Anonymous, est, and 
most modern psychotherapy).
(4,5) It is recognized that such sub-
divisions are arbitrary, and often overlap. Y et these subcategories 
will help us to understand various healing practices that exist on a 
spectrum which includes the supernatural, natural, physiological, 
and psychological.

Spirit mediumship (trance-based healing system)
Spirit mediumship broadly refers to a situation in which the healer or the client, or both, experiences alternate states of consciousness in the form of dissociation or a possessed state at the time of the healing ritual. From a psychotherapeutic point of view, it is

1419
important to distinguish which person is in an alternative state of 
consciousness, as the mechanism of therapy differs depending on whether it is the healer or the client who is dissociating.
(a) Shamanism
It is speculated that the geographic heartland of shamanism is Central and North Eurasia, with widespread diffusion to Southeast Asia and the Americas.
(3) Through a religious ceremony, a shaman

(3) Through a religious ceremony, a shaman 
can work himself into a trance state in which he is possessed by a god. The rhythmic singing, dancing, or praying (quiet meditation) seems to assist the self-induction of the trance state. Among native healers in North and South America, a psychedelic substance (such as may be found in cactus) is frequently used to induce an altered state of consciousness and a special psychic experience for the healing performance. Whether the altered state of consciousness is substance- or self-induced, the healer is considered to be possessed by a supernatural power. The client can then consult the supernat-ural through the shaman for instructions on dealing with his or her problems.
The causes of problems are usually interpreted according to the

The causes of problems are usually interpreted according to the 
folk concepts held by the culture—involving such things as loss of 
the soul, sorcery, spirit intrusion, or violation of taboos. Disharmony 
with nature may also be interpreted as the cause of problems. Coping methods are usually magical in nature, such as: prayer, the use of charms, or the performance of a ritual ceremony for extrac-tion or exorcism. Utilizing supernatural powers, acting as an authority ﬁ  gure, making suggestions, and providing hope are some 
of the main mechanisms for healing provided by the shaman. The goal of the healing practice is to resolve the problems that a client is encountering.
(b) Zar ceremonies
The term zar refers to a ceremony as well as a class of spirits. Zar
ritual is observed primarily in Muslim societies in the Mideast, including Ethiopia, Egypt, Iraq, Kuwait, Sudan, and Somaliland. Zar ritual is different from shamanism in that, in addition to the

ritual is observed primarily in Muslim societies in the Mideast, including Ethiopia, Egypt, Iraq, Kuwait, Sudan, and Somaliland. Zar ritual is different from shamanism in that, in addition to the 
healer, the client also experiences the dissociated or possessed state.
The zar ceremony is primarily a female activity. All of those 
attending the ceremony wear new or clean clothing to please the spirits. The main patient usually wears a white gown, as much gold jewelry as possible, and is heavily perfumed. The ceremony master begins the ceremony with a song and drumming. When a spirit associated with some person in the audience is called, that person begins to shake in her seat, dancing, and trembling until she falls, exhausted, to the ﬂ  oor. Before the spirit consents to leave, it usually 
demands special favours, such as jewellery, new clothing, or expen-

sive foods. It is the duty of the relatives and friends to gather around the prostrate woman and pacify the spirit. The whole tone of the ceremony is one of propitiation and persuasion, rather than coer-cion. The ceremony ends with an animal sacriﬁ  ce and a feast.
The zar ceremony is primarily an adult female activity reﬂ  ecting 
social conditions of sex-separation, low female status, restriction of women from religious participation, an unbalanced sex ratio, marital insecurity, and relative isolation. The zar ceremony provides 
women an ideal situation for relief of persistent and regular anxieties and tensions arising from their life conditions. The goods demanded during the ceremony are all things that their husbands should provide. This fulﬁ  lls a woman’s wish for attention and care. Emotional catharsis, fulﬁ  llment of unsatisﬁ  ed desire, and compen-

sation for the suppressed female role are some of the therapeutic mechanisms working in this kind of therapeutic ritual. Restoring balance in real life is the implicit goal of this culture-embedded healing practice.
(6)
Religious healing ceremonies
A distinction needs to be made between religion and a religious healing ceremony. Religion refers to a system of belief in a divine or superhuman power or spiritual practice. As a part of a religion, some people may perform special ceremonies for the purpose of healing certain problems or disorders. There are various kinds of religious healing ceremonies observed in different societies that are considered by mental health workers to serve a therapeutic func-tion for their participants.
(a) Sprit dancing ceremony
As observed among Salish-speaking Indians of the Paciﬁ  c Coast of

As observed among Salish-speaking Indians of the Paciﬁ  c Coast of 
North America, healing ceremonies utilize psychological mecha-nisms and processes similar to those in brainwashing. The initiate has to go through three major therapeutic approaches: depatterning through shock treatment (such as physical restraint, blindfolding, hitting, kinetic stimulation, or intensive acoustic stimulation, followed by lying still, being forbidden to talk, and starvation); physical training (such as daily running, jumping into ice-cold waters, or frequent rounds of dancing); and, ﬁ  nally, indoctrination.
(7)
(b) Sacriﬁ  cial ritual
An example is found in Y oruba, Africa. A person’s problems were 
identiﬁ  ed by palm nuts tossed by the diviner. It was usually inter-
preted that the person or a member of his family had offended the family orisa  (the lineage deity) or some other spirit. Then, the 
sacriﬁ  ce of a certain animal was prescribed for resolution. In the

sacriﬁ  ce of a certain animal was prescribed for resolution. In the 
sacriﬁ  ce, the supplicant passed his bad luck or illness to the animal, 
and the animal was killed in the supplicant’s stead. The healing power of the ritual lies in its reassurance and generation of conviction. The ritual demonstrates that proper curative steps are being taken.
(8)
(c) The religious ceremony of mourning
This is practised among members of the Spiritual Baptist Church in the West Indies. In a desire for spiritual strength and other beneﬁ  ts, church members volunteer to participate in the practice. 
After ceremonial washing and anointing, the mourners are isolated in a small chamber at the back of the church, where they remain for a period of 7 days. During that time, each individual prays, fasts, and experiences dreams and visions. The mourners claim they obtained beneﬁ  cial psychological relief on their moods; attainment

of the ability to foresee and avoid danger; improvement in their decision-making abilities; cures for physical illnesses; and height-ened facility to communicate with God.
(9)
(d) Snake-handling cult
An extremely different form of religious ritual was a snake-handling cult in the southern United States. As part of cult activi-ties, members, in trance states, handled poisonous snakes as a sign of being blessed by God. Occasionally, some of the members died when they were bitten by the snakes. Although forbidden by the government to perform such cult rituals, these activities still exists. The gratiﬁ  cation of emotional excitement was interpreted 6.5 indigenous, folk healing practices

SECTION 6  treatment methods in psychiatry 1420
as one of the effects sought by cult members—even at the risk of 
their lives.(10)
(e) Christian religious healing
It is important to know that religious healing ceremonies are not only observed in primitive societies or among uncivilized popula-tions, but are quite common in many industrialized societies, as well. In Christian religious healing, there is a broad spectrum of beliefs and activities, ranging from Christian Science to the funda-mentalism of healers such as Oral Roberts to the Roman Catholic rite of anointing of the sick. The participating client is provided with the hope for supernatural resources against disease, thus increasing his or her security and sense of well-being.
(11)
Thus, in various forms of religious healing ceremonies, the 
therapeutic operation is carried out through the ritual of prayer, testimony, sacriﬁ  ce, reliving experience, or even spirit possession.

therapeutic operation is carried out through the ritual of prayer, testimony, sacriﬁ  ce, reliving experience, or even spirit possession. 
Assurance, suggestions, and generation of conviction are some of the healing mechanisms utilized in the practices. The aims of therapy are to heal the problems and give a certain perspective to the client’s life.
Divination
Divination refers to the act or practice of trying to foretell the future or the unknown by occult means. It relies on mysterious, magic, or religious methods. Since the interpretation of divine instruction is usually provided by the diviner himself, or an interpret-er, the interaction between the diviner/interpreter and the client becomes an important variable.
There is a range of methods of divination. Some methods are

There is a range of methods of divination. Some methods are 
very simple, while others are more complicated. For example, in Nigeria, Africa, the divination practised by the Nsukka Ibo (called Afa) is carried out by casting four strings containing half-shells of 
the seeds of the bush mango;
(12) and by the people in Y oruba 
(known as Ifa) by tossing palm nuts.(8) In the divination practised 
in some parts of Africa, the diviner simply offers a certain sign himself. For example, divination may occur while his hand is 
shaking, with the belief that he is guided by a supernatural power to give instructions.
In ancient China, turtle shells or the bones of big animals were 
burned during divination ceremonies and divine instruction was interpreted through the cracks made from the heat. An elaborate divination system called chien  has been developed in China, and a 
modiﬁ  ed version is used in Japan. T o obtain answers to questions

modiﬁ  ed version is used in Japan. T o obtain answers to questions 
about their lives, some Chinese or Japanese will visit temples for 
divination. After a sincere prayer to the god of the temple, the per-
son will ask for divine instruction, which is provided through a for-
tune stick that the person selects. Corresponding to the number on the stick, there is a fortune paper with an answer written on it. This practice is called chien  drawing in Chinese,
(13) or kujibiki  in 
Japanese.
No matter what method of divination is practised , the basic 
therapeutic operation is performed to provide a clear-cut answer for the problems presented. Thus, it is helpful psychologically for a client to ﬁ  nd a deﬁ  nite way to address his problems. Naming effects 
are among the healing mechanisms operating in divination. It is assumed that human life is under the inﬂ  uence of supernatural regu-
lation. It is the basic goal of the person seeking help to ﬁ  nd the

lation. It is the basic goal of the person seeking help to ﬁ  nd the 
proper way to comply with the universe through divine instruction.(a) Fortune-telling
The system of reference shifts from the supernatural to the natural in the practice of fortune-telling. Based on the concepts of micro-
cosm and macrocosm, fortune-telling is oriented to the basic belief that human life and behaviour are parts of the universe. The nature of the problems is usually explained in terms of an imbalance of vital forces or disharmony with the natural principles that rule the universe. The objective of the practice is to help the client ﬁ  nd out 
how to live compatibly with nature and adjust to the environment more harmoniously.
Based on the sources of information used, fortune-telling can be 
divided into several groups. In astrology, there is a basic belief that 
a person’s life is correlated to and inﬂ  uenced by the movement of

a person’s life is correlated to and inﬂ  uenced by the movement of 
the stars, thus, their movement becomes the essential source of information for predicting one’s life course. For the Chinese, an ancient record of universal change, the Oracle of Change ( Yi-Jing ), 
is used for fortune-telling. A person’s date and time of birth, and the number of strokes in the Chinese character for his or her name, is the information needed to calculate an individual’s fortune.
Physiognomy is based on the assumption that there is a close

Physiognomy is based on the assumption that there is a close 
correlation between the mind and the body and that one’s charac-ter, life, and fortune can be read by examining one’s physical features. It is assumed that a person is born with a certain predis-position, which is shown in his physical appearance and will lead him to manifest certain behaviour patterns. A physiognomist tries to help a client understand his own character and behaviour patterns, learning how to make good use of his talents and, at the same time, make up for his shortcomings.
Although the basic assumption underlying fortune-telling is that 
every person has a predetermined course of life, such fate is not absolutely unchangeable—it may be subject to modiﬁ  cation. Thus, 
it is not a completely passive acceptance of fate, but allows room for adjustment. Finding a way to adjust your own fortune is the purpose of fortune-telling.
Even though the basic orientation shifts from a supernatural to a

Even though the basic orientation shifts from a supernatural to a 
natural one, and the sources of practice rely on the rules of nature, the therapeutic operation, like divination, is still characterized by offering folk-natured interpretation and providing concrete guidance for a client in making choices. Based on the concepts of 
microcosm and macrocosm, complying with the fundamental rules of nature is the basic goal of the practice.
Common therapeutic factors
Reviewing various forms of folk therapy, it has been pointed out 
that the core of the effectiveness of different methods of religious and magical healing seems to lie in their ability to arouse hope by capitalizing on the patient’s dependency on others.
(14) Comparing

(14) Comparing 
the healing practices carried out by witch doctors and psychiatrists, it has been pointed out that they share a common root. Both kinds of therapists are able to decrease the client’s anxiety by identifying what is wrong with him—that is, to name the cause of the prob-lems, providing the effect of the Rumpelstiltskin principle; the therapist presents certain personal qualities that are admired by the culture and contribute to the therapy; the client’s expectations of therapy, and the emotional arousal that is usually enhanced by the therapeutic setting, the therapist’s belief in himself, and his 
reputation; the emerging sense of learning and mastery that the

1421
client obtains through therapy; and ﬁ  nally, the techniques of 
therapy that enhance the basic components of psychotherapy. It is clear that folk healing practices and modern psychotherapy share a number of nonspeciﬁ  c therapeutic mechanisms.
(15) It has been 
indicated that traditional healing practices have several advantages 
over cosmopolitan modern medicine, namely: cultural congeniality, maximal use of the personality of the healer, a holistic approach, accessibility and availability (particularly for developing areas), effective use of affect and altered states of consciousness, collective therapy management, and cost-effectiveness.
(1) It is important to 
recognize that both folk healing and modern therapy utilize symbols and metaphors for interpretation and suggestions.
(16) In contrast 
to modern psychotherapists, some folk healers make use of symbolic interpretations and suggestions to enhance the effects of healing.
Attitudes towards indigenous 

Different points of view exist among scholars, clinicians, and public

Different points of view exist among scholars, clinicians, and public 
health workers regarding whether or not to encourage or discour-age indigenous folk healing practices in various societies. Some people (particularly modern clinicians) see folk healing as merely superstitious and primitive, insisting that such out-of-date prac-tices should be discouraged or prohibited. Others (such as cultural anthropologists and cultural psychiatrists) consider these folk practices to be interesting subjects for academic study—examining the therapeutic elements that are utilized in these primitive healing practices, and why such supernaturally oriented therapeutic exercises are still popular among some groups. Still other people (such as some community health workers) believe that, due to the shortage of professional personnel available in the community, the existence of folk therapies should be supported. The position

was taken that any folk healing practice that is proven (or at least considered) to be helpful to the client and useful to the community deserves the support and encouragement of clinicians as well as 
administrators.
Final comments: clinical implications
The comparative study of indigenous healing practices and modern psychotherapy has revealed the existence of certain universal elements of the healing process that operate as important factors for therapy, whether the therapy is carried out in a primitive or modern form. The universal and nonspeciﬁ  c healing factors 
identiﬁ  ed are: the cultivation of hope, the activation of surround-
ing support, and the enhancement of culturally sanctioned coping. The study of indigenous healing practices has also pointed out the existence of supernatural dimensions of healing power, which are less intentionally utilized in modern therapy.
Despite the general usefulness of folk therapies, the ill effects

Despite the general usefulness of folk therapies, the ill effects 
of some have not been widely studied and reported. Y et, clinical observation has disclosed that some folk therapists cause harm to the clients who seek their services. Under the guise of treatment, tricking a client out of his money by deceit or fraud, or sexual involvement with a client, are examples of disreputable behaviour 
that are occasionally reported. Harming a client by prescribing 
dangerous substances, and physically injuring or even killing a client by accident during the performance of an exorcism, are other 
examples of serious complications that have occurred.
No matter what position is taken, there is one simple fact that

No matter what position is taken, there is one simple fact that 
deserves attention, namely, that there exists a wide range of profes-sional quality among so-called folk healers, and different motiva-tions for practice. Some are benign healers motivated by a desire to serve, while others are not. Some are well-trained in their particu-lar professions and know how to practice within its limitations, while others are not—and are liable for malpractice. The major problem is that, from a public health point of view, in most societ-ies, there still are no formal guidelines for regulating folk therapy, as there are for modern therapy. Folk therapy, whether it is sha-manistic practice or faith healing, should be subject to periodic surveys and reevaluation by the public health administration, as is modern clinical work, so that its beneﬁ  ts to clients can be protected

and any potential malpractice can be prevented. If any folk thera-pist refuses to be examined and regulated, he or she should be discouraged or prevented from practicing.
Tseng, W.S. (1999). Culture and psychotherapy: review and practical 
guidance. Transcultural Psychiatry ,36(2), 131–79.
Tseng, W.S. (2003). 7: Culturally competent psychotherapy. In Clinician’s 
guide to cultural psychiatry  (ed. W.S. Tseng), pp. 291–342. Academic 
Press, San Diego.
 1. Jilek, W.G. (1994). Traditional healing in the prevention and treatment 
of alcohol and drug abuse. Transcultural Psychiatric Research Review ,
31(3), 219–58.
 2. Tseng, W.S. (2001). Handbook of cultural psychiatry , pp. 515–37. 
 3. Prince, R. (1980). Variations in psychotherapy procedures. In Handbook 
of cross-cultural psychology: psychopathology , Vol. 6 (eds. H.C. Triandis 
and J.G. Draguns). Allyn and Bacon, Boston.

3. Prince, R. (1980). Variations in psychotherapy procedures. In Handbook 
 4. Tseng, W.S. and Hsu, J. (1979). Culture and psychotherapy. In 
Perspectives on cross-cultural psychology  (eds. A.J. Marsella, R.G. Tharp, 
and T.J. Ciborowski). Academic Press, New Y ork.
 5. Tseng, W.S. (1999). Culture and psychotherapy: review and practical 
 6. Kennedy, J.G. (1967). Nubian zar ceremonies as psychotherapy. 
Human Organization ,26(4), 185–94.
 7. Jilek, W.G. (1976). Brainwashing as therapeutic technique in 
contemporary Canadian Indian sprit dancing: a case in theory building. In Anthropology and mental health: setting a new course
(ed. J. Westermeyer). Mounton Publishers, Paris.
 8. Prince, R. (1975). Symbols and psychotherapy: the examples of

 8. Prince, R. (1975). Symbols and psychotherapy: the examples of 
Y oruba sacriﬁ  cial ritual. Journal of American Academy of Psychoanalysis ,
3(3), 321–38.
 9. Grifﬁ  th, E.E.H. and Mahy, G.E. (1984). Psychological beneﬁ  ts of 
spiritual Baptist mourning. The American Journal of Psychiatry ,
141(6), 769–73.
10. La Barre, E.H. (1962). They shall take up serpents: psychology of 
the southern snake-handling cult . University of Minnesota Press, 
Minneapolis.
11. Hufford, D. (1977). Christian religious healing. Journal of Operational 
Psychiatry ,8(2), 22–7.
12. Shelton, A.J. (1965). The meaning and method of Afa divination 
among the northern Nsukka Ibo. American Anthropologist ,
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SECTION 6  treatment methods in psychiatry 1422
13. Hsu, J. (1976). Counseling in the Chinese temple: a psychological 
study of divination by Chien drawing. In Culture-bound syndromes, 
ethnopsychiatry, and alternate therapies  (ed. W.P . Lebra). University 
Press of Hawaii, Honolulu.
14. Frank, J.D. (1961). Persuasion and healing: a comparative study of 
psychotherapy . Schocken Books, New Y ork.15. T orrey, E.F. (1986). Witchdoctors and psychiatrists: the common 
roots of psychotherapy and its future . Harper & Row Publishers, 
New Y ork.
16. Kirmayer, L.J. (1993). Healing and the invention of metaphor: the 
effectiveness of symbols revisited. Culture, Medicine and Psychiatry ,
17(2), 161–95.

7.1 Public policy and mental health  1425
Matt Muijen and Andrew McCulloch
1452
Tom Burns
7.10.1 The special psychiatric problems of refugees   1493
Richard F. Mollica, Melissa A. Culhane, and Daniel H. Hovelson
7.10.2 Mental health services for homeless mentally ill people   1500

7.10.3 Mental health services for ethnic minorities   1502
Tom K. J. Craig and Dinesh Bhugra SECTION 7
Social Psychiatry and 
Service Provision

7.1
Public policy, and speciﬁ  cally national public policy, is one of the 
key factors that affects the practice of psychiatry, the shape of mental 
health services, and the environment within which mental health services work. The speciﬁ  c content of public policy varies greatly 
across the world and often even across neighbouring countries. It is therefore impossible within the space of this chapter to undertake systematic international comparisons. This chapter gives an over-view of:
(a) what policy is and why it might be important;(b) types of policy and policy development internationally;(c) international structures and organizations that are relevant to 
the scope and content of policy, especially in the ﬁ  eld of human 
rights which is often the starting point for policy;
(d) the breadth of policy activity that is relevant to mental health—

stretching beyond the health ministry and health policy—and the partnerships that are necessary to tackle the mental health of individuals and populations.
What is public policy?
Koontz and Weihrich(1) define policy or policies as ‘General 
statements or understandings which guide thinking on decision making.’ This deﬁ  nition implies that:
1 policy may be stated in writing (statute, guidance, or statement) 
or may be unwritten and disseminated through management or political chains of command only;
2 policies may exist at various organizational levels albeit here we 
are mainly concerned with national policies;
3 policy is only one factor in any ﬁ  nal management or clinical

3 policy is only one factor in any ﬁ  nal management or clinical 
decision. Other factors will often be more important, and clinical behaviour is notoriously resistant to policy inﬂ  uence except 
where certain behaviour is directly prohibited.
(2)
Therefore, the policy needs to be understood as just one of 
the factors which determine the nature and state of mental health services and mental health promotion or public mental health within a society.In many developed countries, the management of the public 
sector has seen major changes over the last two decades, shifting 
from a hierarchical and bureaucratic administration to a model of ‘managerialism’ .
(3) In the old model policy making and administra-
tion was separated, and governments were responsible for the pro-vision of services often via related public sector agencies. The new model, inspired by business,

(4) is characterized by governments 
introducing competition and market principles and involving the private sector in providing services, setting measurable objectives, and introducing performance management with the aim of deliv-ering higher efﬁ  ciency. This has affected professionals such as 
psychiatrists by shifting accountability for good medical practice as judged by peers to reporting on outputs to managers as speciﬁ  ed 
by contracts and practice guidelines. Nevertheless, in most cases strong professional accountability remains, creating a dual accountability that may be appropriate but is always challenging and sometimes conﬂ  icting.
Mental health public policy
Public policy in mental health is driven by a range of inﬂ  uences

Public policy in mental health is driven by a range of inﬂ  uences 
and interests which policy makers will attempt to balance. Positive drivers, that is factors that encourage the development of progressive mental health policies, include:
◆ epidemiological evidence of the prevalence and the contribution 
of mental disorders to the burden of disease;
◆ evidence for effective and efﬁ  cient interventions;
◆ public interest as expressed by politicians and the media;
◆ campaigns by NGOs and professional groups;
◆ human rights considerations;
◆ pressure from patient and family organizations;
◆ growing public expenditure.(5)
The strong interface between mental health issues and human

The strong interface between mental health issues and human 
rights explains the importance of human rights conventions and declarations in the shaping of policies and legislation, especially in countries where mental health policy and practice are less developed historically. Negative drivers, that is, factors that limit the commitment of policy makers, include budget limitations, Public policy and mental health

1426
competition from other priority areas, discrimination, and the 
perception that mental health is not a fruitful area for investment.
The function of mental health policy
Mental health policy may serve a variety of functions ranging from the purely political and presentational through to delivering on a moral or social imperative. Often policy is mixed in function, ena-bling politicians to make a statement on an important human rights or social issue whilst also achieving real improvements for people with mental illness and delivering on economic targets. Mental health policy will also affect delivery of other aspects of policy in relation to crime, housing, education, and health. Thus, a coherent set of social policies cannot be developed without address-ing mental health in some way. Mental health has been called a ‘wicked’ social policy issue (see Bogdanor for a discussion of such issues)
(6) because it is hard to deﬁ  ne, to address, and to deliver on

(6) because it is hard to deﬁ  ne, to address, and to deliver on 
tangibles, but unless we do, many of our social aspirations will not be fully realizable. Finally, the stated mission or desired outcome of policy may vary—for example some countries may have goals in terms of reduced prevalence of an outcome such as suicide, others may wish to achieve de-institutionalization.
(7)
Broader public policy and mental health
Whilst policy on mental health services per se  is likely to be the 
concern of the health ministry, the impact of other public policy on both mentally ill people, and the practical application of psychiatry may be even bigger. People with severe or persistent common men tal 
health problems often face social exclusion and face difﬁ  culties 
with issues including housing/shelter, employment, education, and welfare or welfare beneﬁ  ts. All mental health professionals in all

with issues including housing/shelter, employment, education, and welfare or welfare beneﬁ  ts. All mental health professionals in all 
countries of the world will be aware of how much these issues can affect the lives of people with mental illness and indeed clinical outcomes. Box 7.1.1 summarizes some of the main relevant policy areas which will impact on mental health services.
It should be clear from only brief examination of this table that 
achieving a totally coherent mental health policy presents huge challenges:
◆ The views of different parties and the priorities of many different 
government departments must be reconciled;
◆ Policy must integrate horizontally—for example, across health, 
education, and local government, and vertically from small organizations up to government;
◆ The non-measurable side of what is offered is very important

◆ The non-measurable side of what is offered is very important 
to the stakeholders—services must be responsive, caring, joined up and visible to users, carers, and the general public—yet these features of services are hard to inﬂ  uence from central government;
◆ The needs and demands are so large and diverse it is difﬁ  cult 
to construct and resource a coherent system for delivery even in the richest countries;
◆ Achieving equity and balancing resource allocation across groups 
of people suffering from a range of mental disorders with different prevalence and causing a different burden to self, families, and communities. Different groups of disorders require different invest-ment producing different potential beneﬁ  ts yet such decisions must 
often be made on the basis of ambiguous information whilst sub-ject to conﬂ  icting pressures from advocacy groups, communities,

often be made on the basis of ambiguous information whilst sub-ject to conﬂ  icting pressures from advocacy groups, communities, 
media, colleagues, government ministries, and parliament.Comparative policy
It can be argued that mental health policies in most countries fall within four broad groupings:
1 Provision for the basic protection of human rights of people with 
mental illness or those lacking mental capacity;
2 As one together with a simple health care policy to provide for 
the health care needs of people with serious mental illnesses;
3 The above but with a more comprehensive health and social 
care policy which addresses primary and specialist care needs for various groups of disorders;
4 A comprehensive cross-sectoral mental health policy that address-
es care, public mental health, and broader issues such as housing.
No country in the world has a fully comprehensive policy

No country in the world has a fully comprehensive policy 
although developed countries such as New Zealand, Australia, several SECTION 7  social psychiatry and service provision
Box 7.1.1 Policy links for mental health across government
Government department 
or ministry (generic 
description may not accord 
with structures in all countries)Mental health relevant policy 
responsibility (Examples)
Department of health/health 
and social servicesPrimary mental health care
Human resources for health and 
social care servicesFinance for health and social care
Specialist mental health care 
policyPublic mental health or mental health promotion
Department of employment/
social welfareWelfare beneﬁ  ts for people with 
mental health problems
Employment rights and 
protectionOccupational health
Department of education Education on mental health

Department of education Education on mental health 
issues as part of wider curricula in schools and higher educationHealthy schoolsHigher education for relevant vocational qualiﬁ  cations
Department of criminal 
justice/internal securityDiversion of mentally ill 
offenders from the criminal 
justice systemPublic security
Department of housing/
communities and
local government/regionsHousing for mentally ill people
Community development
Urban policy
Department for 
constitutional affairs/human 
rightsProtection of those who lack 
capacity
Treasury or ﬁ  nance ministry Financing of the above at a 
macro level
Strategic value for money
(The authors after Jenkins et al.  (2002))

1427
European countries, and states of Canada and the United States 
have advanced policies. This reﬂ  ects the nature and resources of 
these societies, and does not necessarily result in differences in prevalence or outcomes.
(8)
Human right conventions and legislation
Human rights have historically been a fundamental driver for the development of mental health policy in most countries of the world. The current Human Rights conventions derive from the United Nations, and are binding once they are ratiﬁ  ed by member

states following adoption by the United Nations General Assembly. The Universal Declaration of Human Rights was adopted in 1948. This was followed in 1966 by the International Covenant on Political and Civil Rights (ICCPR) and the International Covenant on Economic, Social and Cultural Rights (ICESCR), in combination known as the International Bill of Rights. None of the conventions directly addresses issues related to mental health care, although the right to the highest attainable standard of physical and mental health is included in Article 12 of the ICESCR. In non-binding gen-eral comments, the committee on Economic, Social and Cultural 
Rights speciﬁ  ed that right to health covers availability, accessibility

Rights speciﬁ  ed that right to health covers availability, accessibility 
with a strong emphasis on equality and non-discrimination, and acceptability including cultural sensitivity and quality. The obliga-tion of signatories to provide information on detentions and measures taken to prevent abuse for people admitted to mental hospitals is important.
(9)
In 1991, the United Nations General Assembly adopted ‘the prin-

(9)
ciples for the protection of persons with mental illness and the improvement of mental healthcare’ , better known as the MI princi-ples, which remains a key reference document for national mental health legislation. The document outlines 25 principles, stressing the importance of non-discriminatory practice within the health care system. The rights to which patients with mental health prob-lems are entitled, according to the MI principles, include the right to live and work as far as possible in the community, and the right to the best available treatment and care in the least restrictive set-tings in conditions suited to the cultural background of the patient. The principles also set out expectations for conﬁ  dentiality, the pro-
tection of autonomy, and the conditions for involuntary detention. In combination the principles offer a good foundation for modern

tection of autonomy, and the conditions for involuntary detention. In combination the principles offer a good foundation for modern 
mental health policies and legislation. Although the document is 
not legally binding, it is clearly stated that member states are expected to implement these principles fully.
An essential principle, conﬁ  rmed by the World Conference on 
Human Rights in 1993, is that all human rights are universal, equally applying to people with disabilities and mental disorders. This is a strong driver for national governments to deliver anti-discrimination legislation, guidance, and practice.
International agencies
There are several relevant regional agencies that represent coun-tries, including political organizations such as the European Union, the Council of Europe and the European Court of Human Rights, 
the African Commission on Human and People’s Rights, and the Inter-American Court of Human Rights. All have produced con-

ventions and declarations pertinent to people with mental health problems, some legally binding.
(10)The World Health Organization (WHO), the specialist health 
agency of the United Nations, is mandated by its constitution to support member states in all health areas, including mental health. Its core functions include to:
◆ propose conventions, agreements and regulations, and make 
recommendations with respect to international health matters;
◆ assist governments, upon request, in strengthening health 
services;
◆ promote improved standards of teaching and training in the 
health, medical, and related professions;
◆ study and report on, in cooperation with other specialized

services;
◆ study and report on, in cooperation with other specialized 
agencies where necessary, administrative and social techniques affecting public health and medical care from preventive and curative points of view, including hospital services and social welfare.
In 2001, WHO dedicated the World Health Report to mental 
health. The report entitled ‘New Understanding, New Hope’ urges member states ‘to seek solutions for mental health that are already available and affordable’ .
(11) The report formulates a set of 
10 recommendations for member states to address the challenges faced in various areas of mental health. By adopting the report (World Health Assembly Resolution WHA 55.10), governments have committed themselves to implement its recommendations to strengthen primary care and develop accessible and affordable community-based mental health services.

At WHO regional level there have been several declarations and 
action plans that elaborated the principles of the World Health Report 2001, and reinforced the commitment by governments to delivery. Examples include the Caracas Declaration for the Americas, anticipating the World Health Report, and the European Declaration for Mental Health signed in Helsinki 2005.
Why public mental health policy?

Although the governments of most countries accept a role for public policy in the regulation, commissioning, funding, resourcing, and provision of mental health care, particularly for persons with severe and enduring mental health problems, a case still should be made why mental health care cannot be left to a combination of the private market and civil society to deliver without central intervention. As we have argued, when national systems are compared, considerable variation emerges, even within developed countries. In some, the role of government is limited to regulation of independent health insurance groups that purchase from independent providers, and the public funding of a safety net for expensive acute care or long-term conditions. In other countries all parts of the health system are state owned and tax funded.
The World Bank produced a report on this question,
(12) scruti-
nizing the arguments for public ﬁ  nancing of mental disorders as

nizing the arguments for public ﬁ  nancing of mental disorders as 
compared to other conditions that compete for public money. In their opinion, disease burden, cost-effectiveness of interventions, and externalities are not sufﬁ  cient arguments since these are not 
unique to mental health. However, the potential of catastrophic cost, the risk of insurance market failure, and the place of involun-tary treatment and consequent issues of human rights are all disproportionately present in mental health care and plead in favour of a public role. One could add to this that stigma and 7.1 public policy and mental health

1428 SECTION 7  social psychiatry and service provision
discrimination may negatively affect the availability and access 
to mental health services if left to market forces together with the argument advanced above that comprehensive social policies cannot logically leave out mental health.
Economic impact of disease burden

An important argument for the view that mental health should be central to health care and public policy in general is the burden of disease evidence, addressed elsewhere in this book (cross ref). The realization that mental disorders contribute so much to the overall burden of disease puts mental health care at least on an equal foot-ing with other groups of disorders that have long been recognized as posing a major public health challenge such as infectious disease, cancer, and heart disease. Even more startling is the very high pro-portion of years lived with disability attributable to mental health problems and the days lost to employment due to mental health conditions. The majority of mental health problems contributing to disability are anxiety and depression and the burden of substance misuse and organic disorders in developed countries is also very high, and rising.
From a public policy perspective, this means that the conse-

quences of mental health problems are no longer only an issue of health care, but are central to macro-economic national interests, particularly at times of skills shortages. This has become connected with the interest in the mental well-being of the population, based on the observation that level and growth in Gross National Product (GNP) is only very marginally associated with status of mental well-being of the population, and in some cases even inversely correlated.
(13) This has resulted in the conclusion by economists 
that government’s macro-economic policies should not simply be driven by the aim to maximize the Gross National Product and the income of its citizens. Rather, the ‘happiness’ of the population should become the prime driver of policy making.
(14) Governments

(14) Governments 
have consequently seen a need to stimulate the employment of people with mental disorders, both as part of the social inclusion agenda and to reverse the very high and increasing cost of mental disability. This could be considered as a somewhat symptomatic approach ignoring the more systemic problem of job stress and insecurity in very competitive market economies. However, there is also no doubt that loss of employment is a disastrous event for individuals and families in its own right, whether considered from an emotional, social, or ﬁ  nancial perspective. The strong 
association of unemployment with divorce, mental illness, suicide, all factors associated with social exclusion
(15) in their own right,

(15) in their own right, 
supports the case for increasing employment rates, if not exclu-sively so. A challenge mental health services are facing is to identify the most appropriate and effective response to such broader societal needs as many of the levers for change lie outside the health care sector.
The scope of mental health public 
policy development
The scope of mental health policy making has broadened, as 
reﬂ ected in the content of international declarations. During the 
second half of the twentieth century mental health policy and expenditure was focused on people with severe and enduring conditions cared for in institutional settings. Increasingly the focus is broadening to incorporate mental health promotion and 
prevention and treatment of common mental disorders, including 
a key role for primary care. The reasons for this include:

◆ an increased demand for the treatment of stress and depression;
◆ the development of community-based services, lowering the 
threshold to access for, and acceptability of care;
◆ the growing evidence base for a range of interventions such as 
cognitive behavioural therapy (CBT);
◆ increased media interest in common mental disorders and their 
treatment;
◆ the reduction of stigma of common mental disorders;
◆ growing afﬂ  uence in many countries making privately purchased 
therapies more affordable;
◆ an awareness that mental health problems are associated with 
many social determinants of health, including inequality, and macro-economic conditions;
◆ the co-morbidity between mental health problems and many 
physical diseases including diabetes and CHD, affecting mortality, and recovery rates;
◆ an awareness of the cost of mental illness to society, and the

◆ an awareness of the cost of mental illness to society, and the 
evidence of cost-effective promotion and prevention activities.
All these have major consequences for public policy. The complex 
interface between public mental health activities and mental illness services demands a multi-agency approach, crossing the responsi-bilities of government departments and local services and requires 
‘joined up government’ . This requires clear policies with explicit objectives and targets, specifying responsibilities for delivery and 
funding. It requires the active ownership of mental health issues beyond the health care sector and its advocacy by leading practi-tioners across a range of sectors and disciplines.
Policy implementation

The growing range and complexity of mental health-related activitiesrequires explicit strategies outlining the vision and values of reform, the planned service organization, capital and human resource implications, ﬁ  nancing, quality monitoring, and human rights 
protection. The number of countries in the world with such detailed mental health policies as deﬁ  ned above is still low but 
growing. There are also many examples of good strategies, whether at national, state, regional, or local level, that have produced impressive change, and guidance for the drafting of policy and legislation is available.
(16)
The common factors in countries with a successful track record 
of change include:
◆ full commitment by government;
◆ national consultation exercises, gaining the views and support of 
key stakeholders;
◆ clear and consistent communication of objectives;
◆ realistic and sustained resource allocation;
◆ workforce strategies including education and training.

However, there are also examples of countries that have drafted 
comprehensive strategies that have not been implemented.

1429
Failure of implementation will create cynicism that may obviate 
future attempts. Main factors that lead to failure include:
1 Poor connection between the strategy and reality, and lack of 
focus. In some instances strategies are written by foreign experts ignorant of local circumstances. Other examples are of strategies that are based on ideology and are overambitious, repeating the content of declarations without taking into account local needs and resources.
2 Lack of ﬁ  nancial commitment or poor grasp of the ﬁ  nancial 
costs of a new model of care, causing rejection by the ﬁ  nance 
ministry or inability to deliver locally.
3 Neglect of the human resource implications. New models tend to 
require more staff with new skills, and implementation can cre-ate high levels of anxiety that need to be confronted.
4 Lack of consultation with professional groups, users, carers, and 
communities, who therefore reject or resist the strategy.

5 Insufﬁ  cient joint planning either across government or with 
partner organizations that will carry responsibilities for the funding and delivery of essential components such as social care, housing, and employment. Incentives will need to be created for various groups such as professionals and the private sector to support the strategy. Added to this is the need to align incentives across different areas, and to prevent the development of per-verse incentives, leading to conﬂ  icts of interest.
(17)
6 Lack of a long-term perspective. It is often possible to develop 
local model services, but generalization to national and sustain-able programmes requires different approaches.
7 Lack of all party political support. It is unlikely reform will be

7 Lack of all party political support. It is unlikely reform will be 
initiated and embedded within the lifetime of a single parliament/administration or under the governance of the same minister of health. Unless political support is strong across the political spec-trum, the risk of reversal due to weak commitment or even hos-tility to previously agreed plans is high.
Human resources
Any strategy must include plans for sufﬁ  cient staff with the right 
attitudes, skills, and competencies. The growing demand for 
mental health care has increased the need for staff. Many countries 
around the world are looking for ways to remedy staff shortages, particularly of doctors and nurses. Three approaches can be 
distinguished:
◆ increase of national recruitment;
◆ creation of different roles and responsibilities for staff;
◆ international recruitment.

Although the increase of training places is on the face of it an 
obvious approach, it does not solve the problem immediately since the lag time between the creation, for example, of a medical training place and the production of a psychiatrist will be at the least 10 years. The availability of training places assumes that places will be ﬁ lled with able candidates, which is also not always the case. In 
some poorer countries students reject the option to become mental health workers due to stigma, poor working conditions, and poor pay.
An important alternative strategy is to take a more comprehensive 
competency-based approach, and analyse the roles and responsibilitiesof staff groups that are available and could be equally 
effective, sometimes even at lower cost. A potential example of this is nurse prescribing.

(18) A step further is the creation of new 
workforce roles, compatible with the direction of reform. Community-based services may require a multi-disciplinary team involving a larger proportion of social workers and psychologists instead of only doctors and nurses. One could also consider new types of community workers focusing on prevention or early intervention, or support workers for patients with severe and enduring disorders. A primary care-based approach may suggest the development of mental health expertise for primary care work-ers. In practice, however, such models tend to create additional demands for staff and change roles of existing staff, rather than reducing the need for the specialists who remain in short supply.
(19)
A short cut to solving staff shortages is international recruitment,

(19)
A short cut to solving staff shortages is international recruitment, 
setting up a three-way dilemma between ethical recruiting practice, the interest of both receiving and sending countries, and the beneﬁ  t of individuals. In some trade zones the free migration of 
employees, including health care staff, is a basic right. It is also hard to argue that health care staff living in poverty and insecurity should be deprived of the opportunity to improve their lives by working in rich and secure countries. Developed countries argue that it is their responsibility to ensure access to health care for their population, although some consideration for the conse-quences of the country of origin should be shown. Ethical recruit-ment guidelines have been developed, distinguishing between active recruitment, that is deliberately setting out to attract staff, and passive recruitment, offering open opportunities, for example,

by adver tising in an international journal. The presence of a bilat-
eral memorandum of agreement is also a indication of good practice.
(20) It has to be recognized that international recruitment 
is not a phenomenon limited to western host countries. It is a global process, with a stream of staff following the trail of higher salaries.
Funding
If it is accepted that the public sector is responsible for the funding of mental health care, the total amount and by implication the proportion of the health budget to be allocated to mental health has to be determined, whether at a national, regional, or local level. In theory this could be calculated on the basis of a population needs assessment, matching the level of need with the cost of inter-ventions. Many countries have performed epidemiological surveys with a sufﬁ  cient degree of precision to allow an estimate of the 
prevalence of diagnostic groups.
(21) It is more challenging to take

(21) It is more challenging to take 
account of the cost of treatment. Attempts to determine the costs of speciﬁ  c interventions are possible in research settings. 
However, in psychiatry, the cost variation even within homogene-ous diagnostic groups attributable to factors such as severity, age, co-morbidity, ethnicity, geography, and social context, as well as supply factors such as the range of treatments and delivery options, make any prediction imprecise, as demonstrated by the challenge of developing Diagnosis Related Groups (DRGs) for mental health care.
(22)
The variation of spending on mental health across countries is 
striking. About 20 per cent of countries in the world dedicate less than 1 per cent of the total health budget on mental health, and a 7.1 public policy and mental health

SECTION 7  social psychiatry and service provision 1430
few more than 10 per cent as reported in the WHO Atlas project 
(2005),(23) with a strong positive correlation between the mental 
health budget and GDP . Thus, the poorest countries have a very low public spending on mental health, although this ignores the importance of out of pocket payments in many of these countries, sometimes with catastrophic impact on families.
Variations over time of the proportion of health budget allocated 
to mental health tend to be minor. This suggests that proportion of 
budget allocated to mental health can be attributed to static factors such as historical spending, often based on running costs of hospi-tals, adjusted by political priorities and inﬂ  uenced by factors such 
as advocacy and level of stigma. We do not know of any example of a national formula of rational health budget allocation at treasury/ﬁ nance ministry level, although a number of countries use a psy-

chiatric needs index to inform sub-national spending decisions.
Equitable resource allocation

A decision on basis of equity needs to balance the burden of disease for patients, families, and the community (see Chapter 7.5), intensity of human suffering, and the cost-effectiveness of treat-ment relative to other health conditions. In developed countries budgets can be expected to cover basic needs and simple evidence-based practices across all disease groups. It would be hard to accept in Western Europe or North America that patients have no access to treatments for conditions such as tuberculosis or schizo-phrenia. Some rationing in a variety of implicit or explicit forms is usually in place for expensive new technologies or costly treat-ments for common and mild conditions. Whilst mental health has few hi-tech interventions, interventions like CBT would be highly expensive if applied to more than deﬁ  ned subgroups of 
patients.

patients.
In poor countries with very low mental health budgets, many 
lives will depend on the decision how best to invest the scarce resources in order to gain the greatest cost-effectiveness as measured by DALYs averted. Cost-effectiveness studies have found that episodic treatment with older antidepressant drugs is the most 
cost-effective treatment in poor countries, whereas the treatment of 
schizophrenia is relatively more expensive.
(24) Even more challeng-
ing is to decide on the merit of allocation across disease groups, for example, tuberculosis versus mental health.
(25) However, one has to 
take into account that ﬁ  gures are based on averages, and ignore the 
very great personal and community beneﬁ  ts that some individual 
interventions can offer. In mental health, it also has to be considered that interventions are not only about treatment of diseases, but also

interventions can offer. In mental health, it also has to be considered that interventions are not only about treatment of diseases, but also 
involve in many instances action against major human rights abuses and the consequences of neglect, such as patients with schizophre-
nia locked up for years or children ignored in institutions. It is hard to put monetary values on such decisions, and this yet again places mental health activities beyond a narrow health treatment perspec-tive, but shows it as one component of broad public policy making. The challenge is to keep mental health high on the agenda of all public policy makers, rather than it being allowed to slip down every government department’s list of priorities.
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a biopsychosocial perspective . Allyn and Bacon, Boston.Knapp, M., McDaid, D., Mossialos, E., et al.  (2006). Mental health 
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health policy . Greenwood Press, Westport.
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mental health policy . Maudsley Monograph. The Psychology 
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understanding, new hope . World Health Organization, 
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scope for public health sector involvement in mental health . The World 
Bank, Washington, DC.
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Books, London.
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organization of services for mental health . World Health Organization, 
Geneva.

Geneva.
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health declaration for Europe. World Psychiatry ,5, 113–17.
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University Press, New Y ork.7.1 public policy and mental health

7.2
Service needs of individuals 
and populations
Mike Slade, Michele Tansella, 
and Graham Thornicroft
The importance of needs assessment has been one of the most con-
sistent themes to emerge from the evolution of community mental health services. However, the concept of ‘need’ is used in different, and sometimes contradictory, ways. The aim of this chapter is to
◆ deﬁ ne needs assessment
◆ consider different approaches to assessing needs, both at the 
individual and at the population levels
◆ discuss how needs assessments can be applied in real-world settings in planning and delivering clinical care.
Deﬁ ning needs
At its simplest, a need involves a lack of something. But of what? 
In operational terms the concept of need is usually applied to a dif-ﬁ culty (in this case in relation to a person with mental illness) for 
which a possibly effective intervention exists. By implication an experienced difﬁ  culty for which there is no known effective inter-

vention is therefore not deﬁ  ned as a need.
(1) The clearest categori-
zation of such needs was identiﬁ  ed by Brewin, who grouped 
deﬁ nitions of need within mental health care into three categories: 
lack of health, lack of access to services or institutions, and lack of action by mental health workers.
(2) Approaches to need within 
each of these three categories will be reviewed.
(a) Needs for improved health
The psychologist Maslow established probably the best-known hierarchy of need, when he formulated a theory of human motivation.
(3) In his model, fundamental physiological needs (such

(3) In his model, fundamental physiological needs (such 
as the need for food) underpin the higher needs of safety, love, self-esteem, and self-actualization. He proposed that people are motivated by the requirement to meet these needs, and that higher level needs could only be met once the lower and more fundamen-tal needs were met. The clinical relevance of this theory is that it implies a hierarchy of clinical priorities—interventions to meet basic physiological need (e.g. to ensure adequate food supply) should take priority over interventions to foster, for example, self-esteem.In practice health-related needs are often considered in a widely 
deﬁ ned way. In England, for example, the requirement to base the 
provision of services on level of need was ﬁ  rst made explicit in the 
National Health Service and Community Care Act,
(4) which deﬁ  ned

(4) which deﬁ  ned 
need as the requirements of individuals to enable them to achieve, 
maintain, or restore an acceptable level of social independence or quality of life . This requirement was retained when national stan-
dards for mental health services were set.
(5) This involves needs-led
care planning—basing care for an individual patient on an assess-ment of their health and social needs. The needs-led approach offers many beneﬁ  ts:
1 The overall level of need gives guidance about which part of the 
mental health system should treat the patient, for example that people with less disabling mental disorders should be seen in pri-mary care settings.
(6)
2 Needs assessment can improve the comprehensiveness of case 
formulations and care plans by incorporating a broad range of health determinants, such as poor housing or lack of social support.

(6)
3 Explicit identiﬁ  cation of need can support clinician–patient dis-
cussions about care priorities, which is associated with improved treatment satisfaction
(7, 8) and compliance.(9, 10)
4 Identiﬁ  cation of needs helps to identify the contribution of serv-
ices outside the psychiatric sector.
5 Needs-led care can facilitate more individualized treatment plan-
ning than diagnosis-driven approaches, by more closely match-ing the help offered to patient’s needs and by explicitly identify-ing problems which require the involvement of both health and other agencies.
Needs-led care planning focussing on health can be differentiated 
from the assessment of care needs. Assessing care needs involves identifying whether the patient will beneﬁ  t from a predeﬁ  ned

from the assessment of care needs. Assessing care needs involves identifying whether the patient will beneﬁ  t from a predeﬁ  ned 
menu of interventions, and by deﬁ  nition will not identify all unmet 
needs for individual patients. Assessment of need at the patient level should therefore be a separate process from decisions about what care or treatment to provide. There are, however, other reasons to assess needs for services, which we now review.

1433
(b) Needs for services
The second category of need is a requirement for a particular type 
of service. At the population level, it is possible to use epidemiolog ical
methods to develop prevalence for different disorders, which can be translated into estimates of the need for services. A recent epide-miological survey in the United States, for example, found very considerable unmet need of the population level nationwide.
(11)
This study identiﬁ  ed that between 1990–92 and 2001–03 the over-

(11)
all annual period prevalence of mental illnesses remained constant at between 29.4 and 30.5 per cent. Among these cases, however, there was an increase in the proportion who received any treatment at all, rising from 20.3 to 32.9 per cent between the two time periods. The inverse is however very revealing, namely that the most recent data show that 67 per cent of people with mental disorders in the United States receive no treatment. The situation is worse in other countries. A recent comparative international study of depression found that 0 per cent of patients in St Petersburg received evidence-based treatment in primary care, and only 3 per cent were referred on to specialist mental health care.
(12) The 
inability of patients to afford out-of-pocket costs was the primary barrier to care for 75 per cent of the depressed Russian patients studied.
International comparisons of population-level needs have been

International comparisons of population-level needs have been 
conducted in recent years. The ESEMed Study, for example, carried out cross-sectional surveys in Belgium, France, Germany, Italy, the Netherlands, and Spain among 8796 representative members of the general population. Individuals with a 12-month mental disorder that was disabling or that had led to use of services in the previous 12 months were considered in need of care. The study found that about 6 per cent of the sample was deﬁ  ned as being in need of 
mental health care. Nearly half (48 per cent) of these people 
reported no formal health care use, so that 3.1 per cent of the adult population had an unmet need for mental health care. In contrast, 
only 8 per cent of the people with diabetes had reported no use of services for their physical condition.
(13)
(c) Needs for action
In health care, the concept of need has been taken to mean the ability to beneﬁ  t in some way from health care, and thus distin-

(13)
guished from demand (what the person asks for) and supply (services given).
(14) For example, the MRC Needs for Care 
Assessment Schedule is premised on the assumption that need is ‘a 
normative concept which is to be deﬁ  ned by experts’ .(15)
Using this approach, an Australian study compared current and 
optimal treatment for 10 high-burden mental disorders in Australia.
(16) This found that current levels of treatment at current

(16) This found that current levels of treatment at current 
coverage avert 13 per cent of the overall burden attributable to these disorders. Providing optimal treatment at current coverage would avert 20 per cent of the burden, and optimal treatment at optimal coverage would avert 28 per cent. The development of a more robust treatment evidence base makes this innovative approach to informing public policy more possible, and the approach can be recommended for evidence-based policy initiatives.
Patient and staff perceptions of need

There has been a long-standing recognition that differences in perceptions of need can exist, in particular between staff and patient. In the 1990s the emphasis was put on acknowledging these differences, but then prioritizing the staff perspective. For example, UK policy stated that all users … should be encouraged to participate 
to the limit of their capacity. ...Where it is impossible to reconcile different perceptions, these differences should be acknowledged and recorded .
(17) Several societal and scientific developments 
challenge this prioritization of staff over patient perspectives.
First, general societal changes towards consumerism and an

First, general societal changes towards consumerism and an 
emphasis on rights have produced more assertive mental health service users. Easier access by patients to internet-based informa-tion reduces the knowledge disparity. Reduced societal trust in the authoritative expert has eroded the position power of mental health staff. The emphasis put on choice and empowerment raise patient expectations of being more than passive recipients of care.
(18,19)
Second, the prioritization of staff perspectives has been actively 
challenged by an increasingly vociferous and organized user move-ment. This opposition has found its voice in the ‘recovery’ move-ment, which emphasizes the meaning and values of the patient, and the need for services to foster self-management rather than dependency. There has been widespread international policy support for recovery-focussed services

(20) although there can be 
tensions between what professionals construe as their duty of care and being led by the patient perspective on need, which can create ethical dilemmas. Care planning which emphasizes agreement between staff and patients may have additional advantages. A recent study in Verona showed staff–patient agreement on needs was signiﬁ  cantly associated with better treatment outcomes both rated 
by the patient and by staff (psychopathology, social disability, global functioning, subjective quality of life, and satisfaction with care).
(21) Similarly, there is emerging evidence that crisis plans 
(advanced statements) which are jointly agreed between staff and patient can be cost-effective in reducing compulsory admission to hospital.
(22,23) Such emerging ﬁ  ndings indicate that needs assess-
ment and care planning, which are based on negotiation and jointly agreed analyses of problems and interventions, are likely to become increasingly important in future.

Finally, emerging empirical evidence strongly supports the posi-
tioning of the patient perspective at the heart of needs assessment and care planning. Evidence from several studies consistently shows differences between staff and patient perspectives on need,
(24,25)  so 
the two perspectives are not interchangeable. Empirical research sug-gests two reasons for basing care on the patient rather than staff assessment of need. First the patient rating is more stable than the staff rating.
(26) Second, longitudinal studies indicate a causal rela-
tionship between patient-rated (but not staff-rated) unmet need and quality of life.
(27–29) If the goal of mental health services is to improve

(27–29) If the goal of mental health services is to improve 
quality of life, then best available evidence indicates that the patient’s perspective on their unmet needs should drive care planning.
Assessing needs
In this section we identify speciﬁ  c approaches to assessing needs.
(a) Individual-level needs assessment measures
Several standardized approaches to the assessment of patient-level 
need have been developed, primarily in the United Kingdom. These have shown a transition along a continuum, from an initial focus on assessment of need as an objective state to be deﬁ  ned by experts 
following careful assessment, towards those which emphasize the subjective nature of needs assessment.
The earliest standardized needs assessment measure was the 
Medical Research Council Needs for Care Assessment (NFCAS) .
(30)7.2 service needs of individuals and populations

SECTION 7  social psychiatry and service provision 1434
The NFCAS assesses the need for further action by health care 
professionals, and links identiﬁ  cation of a need with a predeﬁ  ned 
list of actions. This raises two problems. First, the emphasis on identifying available interventions which would be at least partly effective is problematic, given the complexities of deciding that a treatment has not worked. Second, updating the list of actions has proved problematic. However, as Bebbington notes, ‘the inevitable value judgements inherent in the procedure have the virtue of being public and consequently accessible to argument’ .
(31) An 
important variation of the NFCAS is the Cardinal Needs Schedule 
(CNS) ,(32) which also considers patient willingness to accept help 
and level of carer concern. Training is needed for using both the NFCAS and the CNS, and they are primarily used for research purposes.
At the other end of this continuum are needs assessment

At the other end of this continuum are needs assessment 
measures which emphasize individual difference and the subjective nature of need. The A VON Mental Health Measure  was developed 
by service users, and assesses physical, social, behaviour, access, and mental health domains.
(33) It can take up to 20 min for completion 
by the patient and 5 min by the staff, and its development has emphasized external validity over other psychometric properties. The Carers and Users Experience of Services (CUES)  was devel-

oped by service users and staff, and assesses 16 domains: the place you live, money situation, the help you get, the way you spend time, your relationships, social life, information/advice, access to services, choice of mental health services, relationship with mental health workers, consultation and contact, advocacy, stigma, any treatment, access to physical health services, and relationship with physical health workers.
(34) Completion can take up to 30 min. Neither 
AVON nor CUES have become widely used in mental health services.
The Camberwell Assessment of Need (CAN)
(35) spans both

(35) spans both 
ends of the continuum. It assesses 22 domains of health and social need, and a key development is that it records staff and patient views separately, without giving primacy to either perspective. Research (CAN-R), clinical (CAN-C), and brief versions (CANSAS) of the CAN have been developed for adults of working age with severe mental health problems,
(36) and it has been translated in 
22 languages. Variants have been developed for people with learning disabilities and mental health problems (CANDID),
(37)
mentally disordered offenders (CANFOR),(38) older adults 
(CANE),(39) and mothers with mental health problems (CAN-M).(40)
An updated web resource for the CAN is available at www.iop.kcl.ac.uk/prism/can.
The CAN has become the most widely used needs assessment 
measure internationally,

(41) and is the standardized needs assess-
ment measure which is most relevant to routine clinical practice. The short version, CANSAS, can be recommended for routine use in community services. Two speciﬁ  c approaches have been empiri-
cally shown to produce patient-level beneﬁ  t. First, the patient-rated 
two-way communication (2-COM) measure is an amended version of the CAN which gives the patient the opportunity to identify unmet needs and also prioritize those which they wish to discuss with their clinician.
(42) Asking patients to complete 2-COM before 
an outpatient appointment and then using that information in the appointment was associated with greater patient satisfaction and more likelihood of treatment change.
(7) Second, a structured

(7) Second, a structured 
approach to collating and feeding back staff and patient ratings for CANSAS and other assessments led to a reduction in psychiatric admissions, probably because of earlier intervention during 
relapse,
(43) and improvements in patient-rated unmet need and 
quality of life for higher premorbid IQ patients.(44) Routine 
use of CANSAS brings patient-level benefits, and empirical evidence indicates the clinical focus should be on assessment and interventions for patient-rated, rather than staff-rated, unmet needs.
(b) Population-level needs assessment measure
Measures to assess population-based needs can be classiﬁ  ed by the

Measures to assess population-based needs can be classiﬁ  ed by the 
data and by the analytic approaches they use. Three types of data are commonly used. The most readily accessible documents the use of current mental health services. While this can be criticized as reﬂ ecting only current service provision, its ready availability and 
nationwide coverage means that is extensively used.
Simple population-based samples are very inefﬁ  cient in estimat-
ing the prevalence of relatively rare conditions such as schizophre-nia. Studies thus tend to use two-stage procedures, with a relatively brief initial screening process applied to a large number of people followed in-depth interviews for a selected few. ‘Booster’ samples, perhaps including all the known psychiatric patients for the areas surveyed, may be sought through mental health services.
(45)
Population surveys depend on the identiﬁ  cation of randomly sam-

(45)
pled individuals. Some types of mental health problems, notably substance misuse, are commonly associated with socially marginal lifestyles, making it likely that sufferers will be systematically under-represented by traditional population sampling approaches. More sophisticated sampling approaches, such as capture–recapture methods, have been used for these situations.
(46)
The third type of data relates to the views of local people. Local 
needs assessment studies entail a structured approach to eliciting the views of service users, their carers, interested voluntary sector organizations, and all statutory agencies with responsibilities in the area. Smith
(47) has described how this type of study can be integrated 
into the overall planning process.
Government initiatives in England have tried to base the alloca-

tion of money between areas on the morbidity as well as the size of their populations. This has led to studies modelling this variation. The ﬁ  rst widely used index
(48) was developed on the basis of con-
sensus between GPs about patient characteristics associated with high use of primary care services. While developed for wider purposes, this was shown to relate reasonably closely to variations in psychiatric admission. Later indices have been established by statistical modelling exercises seeking to quantify the relationship between social variables measured in censuses and either service use,
(49) or population-based epidemiological ﬁ  ndings. The variation

(49) or population-based epidemiological ﬁ  ndings. The variation 
between places in the prevalence of the less severe types of mental illness commonly dealt with in primary care is less than that for problems usually managed by specialist mental health services, which again is much less than that observed for forensic services. Thus models developed for one level of care should not be used to estimate patterns of need for other levels.
In practice, no single approach to assessing the needs of a popu-
lation will sufﬁ  ce. Needs assessment at this level requires the inte-
gration of many perspectives. The Kings Fund review of London’s mental health Services
(50) illustrates how a detailed perspective can 
be assembled from many fragments of evidence, each of which would be inadequate in isolation. Recent examples of population-level needs assessment from the United States, Canada, and

1435
New Zealand also reveal that epidemiological studies may not 
produce data that corresponds directly to needs, and that some sub-populations, for example particular ethnic groups, may be less well represented in such approaches, unless considerable method-ological care is taken.
(51–53)
If a mental health practitioner is asked to join a committee to 
plan services, for example, for a local catchment area, what approach is helpful to identify and use population-level needs? Table 7.2.1 indicates a series of steps to ﬁ  nd the best available information 
on population prevalence rates.
(54)
As Table 7.2.1 shows, we consider that the best possible informa-
tion would be local epidemiological data on the occurrence of mental disorders, using a standard system of classiﬁ  cation, along-
side a measure of the needs for treatment among the prevalent cases identiﬁ  ed.
(55) Since these assessments are expensive and time-

consuming, most sites will not have access to such recent local data. If the data in step (1) are not available then we suggest that coun-try/regional epidemiological data (2) are used instead, and are then weighed for local socio-demographic characteristics. But if such larger scale prevalence data are not available, then a third option is to use international rates from ‘comparison’ countries or regions, again weighted for local socio-demographic characteristics (3). The results in this case will be less accurate because they are based on the additional assumption that the data can be transferred between countries. A newer set of techniques that offer considerable prom-ise are rapid appraisal/rapid assessment techniques. These are methods to undertake brief assessments of population needs which are focussed upon key focussed questions, for example on how primary care services should be augmented to treat people with

depression, and example of these approaches have been used to 
positive effect in South Africa.
(56–58)
In some cases, none of the data described in steps 1–3 will be 
available, and then the next option (4) is to use a number of experts, some of whom may be from the local area, to produce a consensus statement on the local rates and characteristics of people with men-tal illness. Such a data synthesis can be based on the best available views, taking into account local factors (e.g. levels of non-health service provision, family support, traditions, degree of afﬂ  uence, or migration). This pragmatic approach will yield data which are 
accurate enough to use for local service planning purposes.
This raises the important topics of coverage and focussing. 
Coverage  means the proportion of people who receive treatment 
who could beneﬁ  t from it.
(59)Focussing  refers to how far those 
people who actually receive treatment in fact need it: do they have any form of mental illness?

(60) Even in the most well-resourced 
countries one can ﬁ  nd both low coverage and poor focussing.(61, 62)
From the public health perspective, therefore, the key issue is the 
appropriate use of resources, whatever the level of resources actually available, namely to increase both coverage and focus.
(c)  The relationship between individual and 
population-level needs
We have argued in this chapter that the provision of care for indi-

vidual patients should be based on assessment of their health and social needs. Can these individual assessments be aggregated to inform service? For population-level service planning, the key question is what types of interventions to provide, and with what capacity. Therefore data from individual needs assessments cannot simply be aggregated to inform service development decisions. While it is theoretically feasible to undertake routine standardized needs assessments on all patients within a service, this approach alone has three drawbacks. Firstly, despite the developing evidence reviewed earlier about the beneﬁ  ts of routine use of standardized 
outcome assessments, this remains the exception rather than the norm.
(63, 64)  Secondly, there is not yet a sufﬁ  ciently developed

(63, 64)  Secondly, there is not yet a sufﬁ  ciently developed 
information infrastructure to support the national collection, man-agement, and analysis of such data, despite this being a priority identiﬁ  ed two decades ago.
(65) Thirdly, even if individual needs 
assessments were nationally aggregated, the diversity of views (patient, staff, carer, taxpayer) would make a shared interpretation of the data problematic.

In this chapter we have emphasized that it is of central importance when planning mental health service for populations, to do so on the basis of (i) the occurrence of mental disorders in that particular population, (ii) the impairments caused by these disorders that require interventions, (iii) the nature and level of needs among these people, (iv) identifying from among these needs those which are unmet, and then (v) prioritizing new service development on the basis of these unmet needs, including a range of social supports and services (such as housing or employment opportunities, out-side the mental health system), the requirements for enhanced physical/general health care, as well as improvements in the provi-sion of speciﬁ  c mental health services. For all of these sectors there

is an increasingly clear call from service user/consumer groups for involvement in these priority-setting planning exercises.
(18,19)
At the level of individuals with mental illness, there is a similar 
trend to increasingly involve service users/consumers in assessing needs, with emerging evidence that this produces a more compre-hensive basis for care planning. Indeed in the last decade there has been an important conceptual shift away from the view that professionals deﬁ  ned ‘needs’ while consumers stated ‘demands’ , to a 
better appreciation of the many advantages to be gained from identifying, as far as possible, unmet needs in a joint and consen-sual way as a basis for action.Table 7.2.1  Ways to measure or estimate local population mental 
health prevalence
(1)  Actual local epidemiological data on psychiatric morbidity and disability 
for the particular area by age, sex, ethnicity, social status, and degree of 
urbanicity
(if not available)
↓

↓
(2)  Country/regional epidemiological data weighed for local 
socio-demographic characteristics
↓
(3)  International data from ‘comparable’ countries or regions, adjusted for 
local socio-demographic characteristics
(If 1, 2, 3 not sufﬁ  cient)
↓
(4)  Best estimates and expert synthesis and interpretation based on other 
sources of local information and opinions (e.g. extent of non-health service provision, family support, local traditions, or migration)7.2 service needs of individuals and populations

SECTION 7  social psychiatry and service provision 1436
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46. Hay, G. and McKeganey, N. (1996). Estimating the prevalence of 
drug misuse in Dundee, Scotland: an application of capture-
recapture methods. Journal of Epidemiology and Community Health ,
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47. Smith, H. (1998). Needs assessment in mental health services: the 
DISC framework. Journal of Public Health Medicine ,20, 154–60.
48. Jarman, B. (1983). Identiﬁ  cation of underprivileged areas. British 
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of a local index of need (LIN) and its use to explain variations in social services expenditure on mental health care in England. Health & Social 
Care in the Community ,14, 254–63.
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, 1549–56.7.2 service needs of individuals and populations

7.3
Cultural differences 
care pathways, service use, and outcome
This chapter discusses the inﬂ  uence of culture on the route an 
individual takes to access treatment for psychological distress and the treatment received. Culture is difﬁ  cult to measure. All catego-
ries of cultural variables have different meanings and measure different things. Research into them leads to different hypotheses. Given this reality, there is no need to join the cul-de-sac argument of whether one or the other is the most important. In the discus-sion below, the roles of ethnicity and of socio-economic, political, community, national, and other factors that help to deﬁ  ne the 
culture of an individual or a group are acknowledged. Associations with pathways to care, service use, and outcome will be presented.
Care pathways
Cultural variation in pathways through care

At the beginning of the pathway to care, the individual displays cognitive, physical, or behavioural changes. They or their family, friends, or wider community interpret these as in need of some remedy. The individual’s personal resources and then informal resources of family and friends are often triggered to help deal with the problem. These may lead to resolution but if they do not they may lead to presentation through an ever more distant and ‘professional’ array of caregivers, help agencies, and formal medical services. Most help for psychological problems is not given by mental health services. Interventions and their perceived success or failure move an individual along a pathway. 
Pathways through care have differing directions and durations.

Pathways through care have differing directions and durations. 
These depend on where the pathway starts, the presenting symptoms, and psychosocial and cultural factors in the individual, their 
community, and the services used. Pathways are not random, they 
are structured and set by a dialogue between the individual, the community, and the code of the statutory services and the law set within that country.
(1)
At each level the aim of care is to help the individual move down 
to less professional interventions until they are either back in the community or at the lowest intensity of care that meets their 
needs. Traditionally, care pathways have considered routes to 
getting treatment but with de-institutionalization, social inclusion and the recovery model, pathways out of care need to be considered 
more widely.
International comparisons

Cultural variation in pathways to care for a mental health problem is readily, though crudely, demonstrated through interna-tional comparisons. For example, in an international study of the pathways to care of 1554 patients newly referred to the mental health services in 11 centres in different countries, the majority of patients (63–80 per cent) were referred by their general practitioner in United Kingdom, Spain, Portugal, Czechoslovakia, Cuba, Mexico, and Aden Democratic Republic of Y emen. Only between 0–15 per cent of patients in these centres had referred themselves, with the exception of Mexico (24 per cent). In Kenya, only 7 per cent were referred by general practitioners but 72 per cent were referred by a hospital doctor. In Pakistan and India, a quarter of patients were

referred by general practitioners, a quarter by hospital doctors, 
a third were self-referred, and 11–17 per cent were referred by reli-gious healers. In Indonesia, both primary care and native healer referrals constituted each around a third of all referrals. The differ-
ences between these 11 centres largely reﬂ  ected the people’s choice 
of ﬁ rst port of call for a psychiatric problem.
(2)
International differences in pathways are also reﬂ  ected in primary 
health care studies. In a 14 country World Health Organization (WHO) investigation, the proportion of attendees with anxiety and depression as deﬁ  ned by the Composite International Diagnostic 
Interview (CIDI) varied ﬁ  ve-fold across centers. Asian sites reported 
the lowest rates and European and South American sites the highest. The differences in prevalence may reﬂ  ect a combination

the lowest rates and European and South American sites the highest. The differences in prevalence may reﬂ  ect a combination 
of demographic differences between attendees, true differences in population prevalence, the differential availability of other culture-speciﬁ  c pathways to care for the psychologically distressed, and 
differential sensitivity of the CIDI in picking up psychiatric disor-der in different cultures.
(3)
Geographically less dispersed countries also demonstrate signiﬁ  -
cant differences in care pathways. In a recent study of 6 Eastern European countries, the percentage of new patients with schizo-phrenia who ﬁ  rst sought care from psychiatric services ranged

1439
from 69 per cent in Bucharest (Romania) to 47 per cent in Zagreb 
(Croatia). Thirteen percent of patients ﬁ  rst sought care from general 
practitioners in Strumica, Macedonia but 47 per cent in Zagreb. 
The police were the ﬁ  rst port of call in 8 per cent of cases in 
Bucharest but for none in Zagreb.(4)
This study used the ‘encounter form’ developed for the 
WHO which can be used to map and quantify pathways to care 
(Fig. 7.3.1).
Marked differences in pathways to care also exist within coun-
tries and groups. The increase in the use of involuntary admission 
of African-Caribbeans in the UK and African-Americans in the US 
is well documented. The reasons for this are unclear but some argue 
that it reﬂ  ects service conﬁ  guration.(5) More recently, increased 
involuntary admission rates have been reported in the Maori 
population of Auckland, New Zealand.(6)
Geographic and ecological factors may also contribute to varia-

tion in pathways to care within a country. In a Canadian province, 
involuntary admissions were shown to be related to the size of 
a community and its proximity to the hospital. Thus, involuntary 
admission rates were increased if a community was close to the 
hospital. Rates were also higher in both densely populated inner 
city areas as well as in cities of less than 500 people. The higher 
rates of involuntary admission in small towns may be related to a 
decreased likelihood of being tolerated or remaining anonymous.(7)
Despite a similar mental health act, involuntary admissions in 
Greenland were found to be twice as high as they were in Denmark 
or the Faroe Islands. The excess risk was associated with the higher 
homicide rate, lower psychiatric bed availability, lower access to

homicide rate, lower psychiatric bed availability, lower access to 
psychiatric care, small settlements, and increased alcohol consump-
tion and violence in Greenland.(8)
Factors associated with cultural variation in pathways
How interpersonal or cultural factors are translated into differences 
in pathways has rarely been assessed. However, a number of factors 
have been identiﬁ  ed that contribute to cross-national and cross-
ethnic differences.The family may play an important role. An American study 
reported that Chinese patients were kept for extended periods 
of time within their families at the beginning of pathways, while 
Anglo-Saxons and Central Europeans were referred by their rela-
tives or themselves to a range of mental health and social agencies. 
Native Americans tended to be referred by people other than 
relatives or themselves.(9) In another study, both Asians and

relatives or themselves.(9) In another study, both Asians and 
African-Americans showed more extended family involvement, 
and the involvement of key family members tended to be persistent 
and intensive in Asians. Ethnicity was also associated with the 
length of delay, Asians showing the longest delay and white people, 
the shortest.(10)
The history of and the way that institutions promote themselves 
can affect the attitude minority patients have to them and so their 
likelihood of using them. For example, the view of American 
hospital services by ethnic minority patients has been tarnished by 
the American Medical Association’s support for segregated wards 
until the 1960s.(11)
The experience of illness is a culturally shaped phenomenon. 
The monitoring of change, the understanding of symptoms, the

The monitoring of change, the understanding of symptoms, the 
language used to present symptoms, and the fears that accompany 
symptoms are all suffused with cultural interpretations.(12) Cultural 
differences in displaying distress are most obviously seen in 
culture-bound syndromes but are present in the content of delu-
sions and somatic presentation of distress. Somatic symptoms 
are located in multiple systems of meaning that serve diverse psy-
chological and social functions. In one study, the experience of 
neurotic patients in India was labeled depressive by clinicians 
using DSM-IIIR, whereas the patients emphasized their somatic 
experience.(13) Such discrepancies between professional theory 
and patients’ experience may have an impact on the recognition 
and treatment of psychiatric disorder. For example, ethnic 
difference between the doctor and the patient or linguistic/

communication problems had previously been offered as reasons 
for British general practitioners missing depression in South Asian 
women. However, South Asian doctors are also more likely to miss 
Fig. 7.3.1 Pathways to psychiatric 
care in Belgrade, Bucharest, Iasi, 
Strumica and Zagreb. Percentage of 
those taking each step for each centre 
respectively, for carers involved in 
more than 5 per cent of pathways. 
Steps occurring in only one or 
two centres are indicated as a single 
ﬁ  gure followed by the centre name in 
brackets. (Curved arrows above carer 
boxes indicate recursive pathways, 
where patients have gone from one to 
another of the same type of carer). 
Reproduced from Gater, R., Jordanova, 
V., Maric, N. et al.  (2003). Pathways to 
psychiatric care in Eastern Europe.

psychiatric care in Eastern Europe. 
British Journal of Psychiatry,  186, 
529–35, copyright 2003, The Royal 
7.3 cultural differences care pathways, service use, and outcome

SECTION 7  social psychiatry and service provision 1440
depression in South Asian women.(14) Thus, rather than ‘ethnic 
match’ , the culture of medicine may be the important determinant 
of recognition of depression in this group and its treatment. Longer delays in ﬁ  rst contact with a mental health professional,
(10)
reduce likelihood of successful drug treatment,(15) and poorer 
outcomes(16) have been reported in groups of Asian patients. 
The mismatch between patient experience and culture of medicine appears ubiquitous. In Turkey, psychiatric patients with somatic presentations were shown to have longer delays because they went to see hospital doctors ﬁ  rst before being referred to a psychiatrist.
(17)
A study in Nigeria found that a large proportion of depressed 
patients initially received another diagnosis because of somatic presentation.
(18) However, emphasis on somatic experience on the

(17)
(18) However, emphasis on somatic experience on the 
part of the patient does not preclude the patient’s recognition of psychological factors, and addressing culturally shaped experience of illness can help clinicians determine underlying aetiology and understand patients with challenging somatic symptoms.
(19)
Beliefs about why the problem has arisen, shape the pathway into 
care. How important this is depends on how different a culture’s models of illness and treatment are from that of the service providers. For example, in a study of help-seeking behaviour of families of patients with schizophrenia in India, most of those who believed in supernatural causation consulted indigenous healers ﬁ  rst and 
those who identiﬁ  ed schizophrenia as a medical problem consulted 
practitioners of modern medicine.
(20) Similarly, a study in Ghana

(20) Similarly, a study in Ghana 
found that a perceived supernatural cause of mental health prob-lems was associated with a marked reduction in the likelihood of consulting a mental hospital facility.
(21) Surveys among Chinese 
Americans and Mexican Americans show that(22,23)  the association 
between help-seeking, service and acculturation is mediated, amongst others, by beliefs and explanatory models of psychiatric symptoms. Patient satisfaction is highest if the explanatory model of the patient is matched with that of the service provider.
(24)

(24)
Mental health-care professionals are also prone to differences in explanatory models. For example, a comparison between mental health-care professionals in Saudi Arabia and the UK revealed that the staff in the UK believed in a greater range of possible causes and diagnoses for auditory hallucinations than staff in Saudi Arabia. Differences in belief were associated with different expecta-tions regarding efﬁ  cacy of possible treatments.
(25)
Pathways to care are shaped by public opinion and stigma. Such 
factors can also contribute to the resources that a society will give, and where and by whom treatment is given. A population survey in Germany showed that the lay public generally held psychotherapy in high esteem and the vast majority of respondents rejected pharmacotherapy for psychological problems. Psychoanalysis was the most popular approach in the western part of Germany but in eastern Germany the preference was for group therapy.
(26)

(26)
Similarly, because psychiatric practice remains to a large degree 
opinion-based within Europe, differences exist between national 
samples of psychiatrists with regard to the diagnosis, aetiology, 
treatment, and outcome of psychiatric disorders such as schizo-phrenia. Cultural divergence is especially evident with regard to differential emphasis on psychodynamic and biological approaches,
(27) and the level of availability of psychotherapy within 
the health service in European countries appears to be associated with the dominant therapeutic culture of psychiatrists.
(28)
The quality of mental health legislation, and, perhaps more 
importantly, the degree to which correct implementation is enforced have an effect on care pathways. Increased stigma of 
psychotic illness and fear of public safety have led to compulsory treatment in the community becoming law in the UK. This could change pathways to and through care.
(29) In the Netherlands,

(29) In the Netherlands, 
a weak and impractical act has been criticized for denying patients with severe mental illness the treatment they need. In Spain, to date no speciﬁ  c mental health act exists. In countries like the United 
Kingdom and France, involuntary admission is in practice, a largely clinical decision, and therefore more easily to put into effect compared with, for example, The Netherlands and most of Germany where the decision is ultimately made by the judiciary. In the United Kingdom and France, the police may bypass medical referral and take people behaving strangely in a public place direct-ly to a psychiatric hospital. This has been shown to be an important pathway for certain ethnic minority groups, such as African-Caribbeans in the United Kingdom.
(30)
Filters on the pathway to care and 
service use

(30)
Filter permeability and service use
The majority of people in psychological distress never present to 
formal health services. If formal help is sought, the likelihood of receiving such help is inﬂ  uenced by the permeability of a number 
of ﬁ lters (see Chapter 7.8). For example, once the decision to seek 
formal help is taken, actual receipt of help depends on the ability of the professional at the ﬁ  rst port of call (usually primary care 
services) to recognize the presence of mental disorder. The perme-ability of subsequent ﬁ  lters determines the rate with which patients 
move from primary care service to specialist mental health out-patient services, and from specialist outpatient to hospital-based psychiatric services and back down the hierarchy.
(a) Cross-ethnic differences
There are important cross-ethnic and cross-national differences in the permeability of ﬁ  lters along the pathway to care. Recognition of

There are important cross-ethnic and cross-national differences in the permeability of ﬁ  lters along the pathway to care. Recognition of 
symptoms by mental health professionals is an important factor. Recognition of distress is dependent on the way symptoms are elicited. For instance, the recognition by primary care doctors of psychiatric disorder in African-Caribbeans and South Asians in the United Kingdom has been shown to be poor.
(31) There are a num-
ber of reasons for this including differences between the symptoms expected by doctors and those presented.
(12) Despite the fact that

(12) Despite the fact that 
they visit their general practitioner more often, women of South Asian origin with depression are less likely to be diagnosed and treated than white British women. Detection of depression depends on the doctor’s skill but also whether the patient tells the general practitioner about her worries. Those who believed that a doctor was the right person to deal with depression were found to be more likely to disclose information and more likely to be diagnosed and treated.
(12) South Asian women are less likely than white 
British women to think that a doctor was the right person to deal with depression.
(32) A one-year follow-up of the sample of the

(32) A one-year follow-up of the sample of the 
Epidemiologic Catchment Area Program revealed that African-Americans, Hispanics, and other minorities were much less likely to have consulted with a professional in the specialized mental health care sector than white people. The odds of consultation in African-Americans was less than one-quarter of that in white people even after adjustment for confounders.
(33) Similarly,

1441
African-American children and adolescents may also remain 
under-treated although they may have higher levels of symptom-
atology.(34) Differences between American ethnic groups are also 
apparent in populations with identical insurance coverage.(35)
Hence, these ﬁ  ndings(36) suggest low permeability of ﬁ  lters on the 
pathway to mental health care. Reasons for this may include that African-Americans are less inclined to seek professional help because of increased tolerance to depressive symptoms, but also because of fear of hospital admission.
(37) In comparison to all other 
ethnic groups, African-Americans make more use of emergency rooms for routine psychiatric care.
(38)
Despite the low permeability of the ﬁ  lters on the pathway to

(38)
Despite the low permeability of the ﬁ  lters on the pathway to 
care there is an over-representation of African-Caribbeans and African-Americans at the level of hospital-based psychiatric services. Possible mechanisms for this include failure of commu-nity services to engage mentally ill African-Caribbean men
(39) and 
bypass of the usual ﬁ  lters by, for example, compulsory admission 
to hospital with or without police involvement.(40) It has been 
shown that police involvement and compulsory admission to hospital is strongly associated with the absence of general practi-tioner involvement.
(41) Levels of perceived violence and rates of

(41) Levels of perceived violence and rates of 
involuntary admission may be due to stereotyped attitudes of the police and mental health professionals or may be in part due to a higher rate of presentation of psychosis that is superimposed on intact premorbid personalities. It has been suggested that reactive forms of psychotic illness in African-Caribbeans are wrongly labelled as schizophrenia.
(42) Higher functioning, less 
withdrawn patients may be perceived as constituting a higher risk by police and mental health professionals. Another factor is that, despite low rates of recognition by general practitioners, African-Caribbeans are most likely to be referred on to a specialist, followed by white people and then people from south Asia even when socioeconomic class and diagnosis are taken into account.
(31)(b) Cross-national differences

Cross-national differences in ﬁ  lter permeability and service use are 
difﬁ cult to examine. Service organization plays an important role. 
For example, compared with south Manchester, in the United Kingdom, closer integration between community and inpatient psychiatric services in south Verona, Italy, resulted in a greater per-
meability of the ﬁ  lter between inpatient and community care, as 
evidenced by higher hospital admission rates and shorter lengths of stay. Conversely, greater permeability of the general practitioner referral ﬁ  lter in south Manchester resulted in more referrals, and 
therefore higher treated incidence and prevalence rates of psychiatric disorder.
(43) Similarly, compared with the more institution-based 
system in Groningen, in The Netherlands, the south Verona community-based system provided for a higher degree of continuity of care across services for patients with schizophrenia.
(44)

(44)
Because of convergence in methodology, fascinating material on 
cross-national differences in the dynamic balance between psycho-logical distress, need for care, and actual treatment received is now available from large prevalence surveys of representative samples in different countries. Comparative data are available on three large population studies in three countries. In the United States and Ontario (Canada), samples representative of all non-institutional-ized individuals aged 18 to 54 years were examined using the Composite International Diagnostic Interview (CIDI) in 1990 and samples of people aged 18 to 64 years in The Netherlands were examined in 1996 (Nemesis Study).
(45–47)
The three studies show that help-seeking rates among individuals

(45–47)
The three studies show that help-seeking rates among individuals 
with a diagnosable disorder vary widely. The contact rate with any type of formal or informal service was lowest in the United States (33.9 per cent) and not far from twice as high in The Netherlands (56.7 per cent) (Table 7.3.1). Among individuals with a diagnosable disorder, ambulatory service use in the general medical sector was much higher in Ontario and The Netherlands than in the United States, especially among those with more severe comorbid 
Table 7.3.1 Prevalence of CIDI disorder and service use in three countries
Service use
12-month 
prevalenceGeneral medicalaAmbulatory mental healthbAny service Perceived need for care in non-
users of professional services
National Comorbidity Survey
No disorderc54.0 2.6 2.6 7.6
One disorder 1S.7 5.6 8.3 18.8 8.4Two disorders 12.0 10.2 18.6 33.9
Ontario
No disorder’ 65.6 1.5 1.2 3.3One disorder 127 9.7 6.3 17.8 5.4Two disorders 5.9 24.3 23.5 39.4
Nemesis
No disorder

Ontario
Nemesis
c 58.8 3.8 1.8 6.1
One disorder 15.3 15.5 7.8 22.5 3.8Two disorders 8.1 42.8 30.3 56.7
a Non-psychiatrist physician in any setting or allied health professional in a general medical setting.
b Psychiatrist or psychologist in any setting or allied health professional (e.g. nurse, social worker) in a psychiatric or addi ction treatment setting.
c No lifetime history of any disorder at all.
Weighted data from Kessler et al.(45) and Bijl et al.(47)7.3 cultural differences care pathways, service use, and outcome

SECTION 7  social psychiatry and service provision 1442
disorders. Individuals in the United States with more severe disor-
ders were less likely to use services in the health-care sector as a 
whole, but if treatment from self-help and other sources is included, the difference between Ontario and Nemesis on the one hand, and the United States on the other, is attenuated. This suggests that low permeability of the primary care access and primary care referral ﬁ  lters in the United States may lead to increased use of 
non-professional services to ﬁ  ll the gap.
Table 7.3.1 shows that the higher the contact rates with profes-

sional services of individuals with a CIDI diagnosis, the lower the number of individuals who were not using professional services but felt they were in need of such help (level of unmet need) (Table 7.3.1). Such differences in the population level of unmet need are important from the point of view of public health. For example, if 90 per cent in a population of 200 million are non-users of professional services for mental health problems, then the difference between 8.4 per cent (United States) and 3.8 per cent (The Netherlands) in perceived need is a difference of 9.2 million individuals.
The substantial differences in mental health care provided by the 
general practitioner are likely to have an equally substantive impact on the likelihood of receiving appropriate management. Thus, the proportion of patients with major depression (as deﬁ  ned in

general practitioner are likely to have an equally substantive impact on the likelihood of receiving appropriate management. Thus, the proportion of patients with major depression (as deﬁ  ned in 
DSM-IIIR) in the previous 12 months who received appropriate medication management, deﬁ  ned as a combination of antidepres-
sant medication use and four or more visits to any health-care provider within the previous 12 months, was much higher in Ontario (14.9 per cent) than in the United States (7.3 per cent). 
This difference was especially marked for the lowest income groups 
in the two countries. Individuals in the lowest income groups in the United States were found to be 7.5 times less likely to make contact with either general or specialty health-care providers than their peers in Ontario. For the highest income groups, however, contact rates differed only by a factor 2.1.
(48) These data suggest

(48) These data suggest 
that economic barriers play an important role in determining the permeability of the ﬁ  lters on the pathway to care. In a United 
Kingdom national survey, 16 per cent of patients with a depressive episode in the past week according to the Revised Clinical Interview Schedule were current users of antidepressant medication.
(49)
Because the majority of the population does not have a mental 
disorder, even a small degree of service use by this large segment of the population will take up a considerable part of the total capacity of mental health services. Thus, Katz et al.
(50) noted that because of

(50) noted that because of 
the relatively high rates of perceived need for care and help-seeking among individuals without a CIDI diagnosis in the United States, total mental health outpatient service use was higher in that country than in Ontario. Although diagnosis is only an imperfect indicator of need for care, the results nevertheless suggest that the mismatch between need and care in the population is greater in the United States than in Ontario.
A long-standing debate exists whether and how ﬁ  nancing of 
mental health care can be used to maximize the ﬁ  t between need

mental health care can be used to maximize the ﬁ  t between need 
and care in the population. A frequently expressed concern is that universal coverage will lead to an increase of people with little need using services of unproven value. The opposite argument, however, is that limitations in coverage will result in service use that is poorly matched to need. Although it is thought that differences in type of insurance system have an impact on demand and utiliza-tion of mental health services,
(51) systematic comparisons between countries have been lacking. The systems of coverage in the United

States, Canada, and The Netherlands are different in many respects. In Ontario, universal and relatively comprehensive coverage for mental health services exists, with no or minimal limits on inpatient stays or outpatient visits for mental health services, and minimal patient cost sharing. In The Netherlands, almost all mental health care is covered under the Exceptional Medical Expenses Act, and is available to the entire population. A compre-hensive range of public services exists, with few supply-side controls. In the United States, at least 16 per cent of the population is uninsured, and even for the insured mental health coverage is increasingly limited. Although the public health system provides mental health care at little or no cost to the poor and the unin-sured, supply-side controls severely and increasingly limit access. Therefore, the results of the comparisons between the three coun-tries do not support the frequently expressed reservation that

expansion of insurance coverage for mental health disorders results 
in an increase in unnecessary use of services. Of the three countries considered, those with broad mental health coverage actually treat-ed a similar number or more people with severe mental illness, but less people who never had a history of mental illness.
Treatment and response
Culture has an important inﬂ  uence on the type of service received. 
There are reports that African-Caribbean and African-American patients receive antipsychotic medications in a higher prescribed dose, and more frequent use of injectable preparations is made.
(30, 52–57) Asian patients have been reported to receive lower 
doses.(58, 59)  Some ethnic minority groups may receive less infor-
mation about side-effects,(60) which may result in less vigilance 
with regard to onset of problems such as tardive dyskinesia. In the United States and the United Kingdom, ethnic minority patients are less likely to receive psychological treatment.

(61,62) In the United 
States, African-American children have substantially lower rates of receiving methylphenidate.
(63,64) Such differences may be 
related to differences in explanatory models of African-American parents, and differences in the rate with which African-American parents receive appropriate information about attention deﬁ  cit–
hyperactivity disorder from the doctor.
(65)
There are several important considerations with regard to 
outcome in relation to cultural variables.(66) The ﬁ  rst is that 
services offered may not be equally efﬁ  cacious for different groups

services offered may not be equally efﬁ  cacious for different groups 
of people. For example, Chinese, Japanese, Filipino, Korean, and Southeast Asian Americans who were treated in the same setting in Los Angeles County showed different outcomes. Filipinos were under-represented in the system, whereas Southeast Asians were over-represented and had higher rates of service utilization. Despite this, Southeast Asians showed less improvement than the other groups, even after controlling for diagnosis and initial level of functioning.
(67) The second is that treatment uptake may differ 
between groups.(33) In the United Kingdom and the United States, 
uptake of treatment with antipsychotic medication may be higher in white patients, though the overall inﬂ  uence of ethnicity remains 
small.
(68) The third consideration is that the expectations about the

small.
(68) The third consideration is that the expectations about the 
desired endpoint of treatment may not be the same for different groups of people. For example, the expectations of British Asian and white people relating to the process and outcome of a psycho-logical intervention were shown to be different in one study.
(69)

1443
Outcome may improve if therapists receive information about their 
clients’ cultural background and expectations before treatment.(70)
Perhaps the most important consideration is that outcome is a 
multidimensional concept defying summary statements. For example, clinical outcome in terms of usual symptom severity and risk of self-harm may be better in African-Caribbean patients with psychosis as compared with white people, yet risk of imprisonment and compulsory admission may be greater,
(71) as may be the 
frequency of relapse(72) and the rate of dissatisfaction with 
services.(73)
However, it is interesting to note that a recent pan-European 
study has concluded that despite the fact that differences in health-care systems may affect service provision and cost, the impact of such differences on outcome may be less marked. More work needs to be undertaken on cultural differences in care pathways and treatment to see if they change outcomes.
(74) Moreover, at an

(74) Moreover, at an 
individual level, recent work has failed to show differences in the duration of untreated psychosis between African Caribbeans and whites in the UK,
(75) even though they have different pathways 
to care at ﬁ  rst admission indicating that the impact of cultural or 
ethnic differences in pathways can be difﬁ  cult to predict.
Pathways out of care
Pathways out of care are complex and have multiple inﬂ  uences. 
An important inﬂ  uence is the pathway into care because the 
relationship set up with services at ﬁ  rst contact determines, in part, 
the trajectory of the clinical career of a patient. Moreover, in speciﬁ  c circumstances, such as where the criminal justice system is 
involved, certain responsibilities may be placed on services which constrain the ability to discharge patients. There has been little research which aims to understand ethnic differences in pathways out of care.
(76) This reﬂ  ects the fact that the focus of studies to date

(76) This reﬂ  ects the fact that the focus of studies to date 
has been to document any inequalities in access to care.
Pathways out of statutory sector care are inﬂ  uenced by the 
effectiveness of treatment strategies, the illness models and treat-ment preferences of patients, the structure and funding of clinical services, the availability of and access to nonstatutory sector support and also the socio-cultural context in which people live.
Effectiveness is a combination of the efﬁ  cacy of a treatment 
and the real world context which inﬂ  uences outcomes. Though 
there may be differences in the efﬁ  cacy of drugs by racial group, 
differences in compliance are more likely to be important,
(77) and 
there are well documented differences in adherence to treatment programs which may lead to differences in rates of patients leaving care.
(78)
Adherence has been linked to differences in illness models but

(78)
Adherence has been linked to differences in illness models but 
in psychosis the level of discord between patient and treatment ser-vice illness models are not consistently associated with differences in outcome.
(79) This may reﬂ  ect the fact that preferred alternative 
treatment outside statutory mental health services are not available or that services are more coercive with patients who do not fully subscribe to their model.
The structure and funding of clinical services is important. Filters 
out of care can be porous—an example of this is Ontario, where rehabilitation is mainly offered by local community based organi-zations which may have better links with the community and so make transition out of care easier. They also have limited responsi-bility for their clients compared to the UK and may be less risk averse. Risk averse service cultures can lead to delay in discharge from care.
(80) Moreover, putting the onus on risk can mean that

(80) Moreover, putting the onus on risk can mean that 
ethnic groups who are considered more risky have particular difﬁ  -
culty in getting out of care.
Prevailing law also shapes pathways out of care. Such laws 
may be applied differently to some ethnic groups. For instance, in 
New Zealand, the Maori population is more likely to be detained on community treatment orders thus delaying movement out of statutory service care.
(81)
The availability of nonprofessional support and the structure of

(81)
The availability of nonprofessional support and the structure of 
some cultural groups may affect pathways. Those of South Asian origin with severe mental illness spend less time in hospital and outpatient care. Family support is cited as the reason for this. Socio-cultural mores are important but also geographic concentra-tion; dispersed refugee and asylum groups with limited access to community support may stay longer in services than would be expected from their symptoms. But socially cohesive groups can be a double-edged sword. One study has demonstrated higher rates of re-admission in areas with high social capital which arguably could be a result of high levels of health norm policing and low levels of tolerance for deviance.
(82)
Socio-economic factors also need to be kept in mind when con-

(82)
sidering the capacity of communities to offer care. The decreased resources available to low income groups will be important in determining the level of burden they will be able to accept.
World Health Organization: up to date information on the health with 
a good archive, research tools and data as well as a section which summarizes health systems organization and funding for each of the countries in the world. http://www.who.int/en/
World Association of Cultural Psychiatry: free newsletter and journal on 
cross cultural psychiatry issues at: http://www.waculturalpsychiatry.org/
National Institute for Clinical Excellence in the UK has developed a 
pathways approach to improving mental health services for people with schizophrenia backed by algorithms and research evidence: 
http://www.schizophreniaguidelines.co.uk/nice_implementation/
pathways_to_care.php.

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7.4
Primary prevention of 
Despite the demonstration of the possibility of preventing some 
forms of mental disorders, many mental health professionals con-tinue to underestimate the possibilities of primary prevention in their ﬁ  eld. This is due to:
1 a lack of clear concepts when referring to this issue;2 the fact that the effective prevention of mental and neurological 
disorders often falls outside the usual remit of mental health professionals (in many cases it falls outside the health sector altogether).
These two factors are discussed below, in addition to an 
indication of actions which effectively prevent some forms of mental disorders.
In the late 1950s, Leavell and Clark(1) proposed a three-level con-

cept of prevention (primary, secondary, and tertiary), covering almost all medical actions. Their innovative approach must be understood in relation to what they also called the horizon of the natural history of the disease process: under natural circumstances, a disease will proceed from a prepathological period through its early stages, evolving either to partial or full recovery (or cure), or to death; in the case of partial recovery, there may be chroniﬁ  cation 
or sequelae. Prevention, in this sense, refers not only to the appear-ance of the disease but also to any further worsening or complica-
tion of it once it has appeared.
Primary prevention
The primary prevention level covers what is otherwise referred 
to as both health promotion and speciﬁ  c protection, and is best

to as both health promotion and speciﬁ  c protection, and is best 
exempliﬁ  ed by, for example, adequate nutrition and immunization 
against speciﬁ  c diseases by vaccines. Whereas, in this example, 
adequate nutrition is totally non-speciﬁ  c (it contributes to enhanc-
ing the overall resistance to several diseases without conferring any speciﬁ  c protection against any), vaccination is highly speciﬁ  c 
in relation to a single condition. Rational-specific protection is fully dependent on a reasonable knowledge of the aetiology of the disease (or, at least, its mode of transmission) in order to be effective.Secondary prevention

The secondary prevention level refers to early detection and treat-ment of diseases. Usually the bulk of the medical activity, its main preventive goal is to avoid chronicity and the establishment of irreversible sequelae. It is dealt with more speciﬁ  cally in Part 6 of 
this book.
Tertiary prevention
The tertiary prevention level largely corresponds to rehabilitation. It enters into operation once the disease process has been estab-lished and aims at reducing as much as possible damages caused by the disease process, preserving intact functions, and restoring and/or compensating impaired functions, disabilities, and handicaps.
On one hand, this conceptual model was highly instrumental in 
providing an impetus towards preventive activities in the medical ﬁ eld as a whole but, on the other hand, it so popularized the term

providing an impetus towards preventive activities in the medical ﬁ eld as a whole but, on the other hand, it so popularized the term 
prevention that it almost lost its powerful message. Therefore, it is important to retain the idea of primary prevention as a synonym of speciﬁ  c protection, referring to methods designed to avoid the 
occurrence of a speciﬁ  c disorder or groups of  disorders. It comprises 
those measures applicable to a particular disease or group of dis-eases in order to intercept their causes before they affect people, and should be differentiated not only from treatment and rehabili-tation, but also from mental health promotion.
The main obstacle for the prevention of many mental disorders

The main obstacle for the prevention of many mental disorders 
is the limited knowledge about their aetiology. Admittedly, there are very promising and exciting hypotheses concerning the causes of three mental disorders which represent the greatest burden, namely, depression, schizophrenia, and dementia. They are, never-theless, nothing more than hypotheses. The most successful examples of prevention of diseases refer to those whose aetiology (cause and/or mode of transmission) is relatively well-known. There are historical examples of the prevention of some conditions based on false assumptions about or without a good knowledge of their aetiology (for example, the eradication of malaria in ancient Rome, and the control of the London cholera epidemics by John Snow in the nineteenth century). However, it does not seem appro-priate for health professionals and scientists to base their actions on chance or false assumptions, even though the result might be opportune to the population.

1447
As implied by the need to intercept causes of a particular disease 
or groups of diseases (with a common cause), the concept of pre-vention calls for a high degree of speciﬁ  city concerning the target 
condition or conditions. In the medical ﬁ  eld, it led to successful 
programmes for the prevention of, for example, diarrhoeal diseases (such as typhoid), hypertension, coronary heart disease, breast cancer, and unwanted pregnancies, rather than of infectious dis-eases, cardiovascular diseases, cancer, or obstetrical problems. Unfortunately, in the mental health ﬁ  eld there has not been a great 
concern with the speciﬁ  cation of the target condition, and the 
prevention of ‘mental disorders’ (as a whole) became a label soon associated with failure and disinterest.
Mental disorders

What is understood as ‘mental disorders’ comprises a variety of quite diverse clinical conditions in terms of aetiology, symptom-atology, clinical course, prognosis, and response to treatment. Therefore, whenever the prevention of mental disorders is referred to, an effort must be made to obtain some precision.
From a nosological point of view, most of the mental disorders 
are conceptually at a syndromal level; depression, schizophrenia, and dementia are appropriate examples. In this respect, dementia is one step ahead of the other two, in so far as vascular dementia is now clearly differentiated from Alzheimer’s disease, with impor-tant implications for prevention.
Therefore a strategic shift is necessary in order to obtain greater

Therefore a strategic shift is necessary in order to obtain greater 
efﬁ ciency in the successful prevention of some mental disorders. 
The ﬁ  rst step is for an effort to be as speciﬁ  c as possible in relation 
to the target condition: for instance Down syndrome or phenylke-
tonuria instead of intellectual disorder, foetal alcohol syndrome, delirium tremens instead of alcoholism, and vascular dementia and dementia following brain injury instead of dementia in general.
The second step applies to those conditions which cannot be 
meaningfully broken down into more speciﬁ  c conditions, such as 
schizophrenia or depression. In these cases, the target is displaced from the appearance of the conditions towards future relapses, once a ﬁ rst episode has occurred; this conveniently applies to schizophre-
nia, depression, and dependence on alcohol and other drugs.
Finally, there are some violent behaviours, such as suicide, para-

suicide, and violence against others, the control (and prevention) of which are largely expected by society to come from the ﬁ  eld 
of mental health. They do not characterize a mental disorder in particular, but are frequently associated with one or more of them. Their prevention, therefore, requires specifically dedicated interventions.
With this wide range of issues considered as mental disorders, it 
becomes clear that the coverage of their prevention goes well beyond the limits of this chapter. A detailed conceptual approach to the prevention of mental and psychosocial disorders can be found in a recent publication of the World Health Organization (WHO ).
(2)
Prevention of mental disorders
From a practical point of view there are three groups of conditions 
for which efﬁ  cient preventive action has been documented.

(2)
1 Mental disorders with known aetiology: this mostly includes 
those disorders demonstrated to have an organic basis, ranging from the ‘historical’ general paresis and dementing disorders 
(e.g. vascular dementia, pellagra, and dementias associated with infectious and parasitic diseases such as malaria and HIV infec-tion) to several forms of intellectual disorder (Down syndrome, foetal alcohol syndrome, phenylketonuria, and intellectual dis-
order due to iodine deﬁ  ciency).
2 Mental disorders without a well-established aetiology but with 
a relatively predictable course: these are chronic disorders with a recurrent relapsing ﬂ  uctuating pattern, such as schizophrenia, 
mood disorders (unipolar and bipolar), and alcohol dependence 
syndrome.
3 Psychosocial problems strongly associated with mental disorders:

syndrome.
3 Psychosocial problems strongly associated with mental disorders: 
these range from violence (domestic and other) to suicide and staff burnout.
Mental disorders with known aetiology
(a) Infectious diseases
Prevention of this group of disorders has by far yielded the greatest success. The demonstration in 1911 by Noguchi and Moore of the brain infection by Treponema pallidum  as the cause of general 
paresis
(3) opened the way in 1917 to its treatment by malaria thera-
py, and later to its prevention with penicillin; this is now a land-mark in the history of medicine. The discovery of the aetiology of pellagra also led to its prevention and control, leading to the pre-vention of one type of dementia associated with alcoholism and avitaminosis.
These two once very frequent diseases have almost completely

These two once very frequent diseases have almost completely 
disappeared and there are many experienced psychiatrists who never come across a single case of either; with them also disap-peared the history of their successful control. Although the same success has not yet been achieved in relation to vascular dementia, the control of hypertension and atherosclerosis (e.g. through the reduction of salt and fat intake) can signiﬁ  cantly reduce brain dam-
age and ensuing dementia (vascular or multi-infarct dementia).
In some developing countries, meningitis and malaria (and, to 
a lesser extent, inadequately treated epilepsy) are important causes of permanent brain damage which can also lead to dementing 
disorders. The environmental control of malaria and other brain infections, of which bacterial meningitis is the most important,

disorders. The environmental control of malaria and other brain infections, of which bacterial meningitis is the most important, 
and their early and prompt treatment can reduce the impact of the infection on the brain and prevent these forms of dementia (or intellectual disorder, depending on the age of onset).
More recently, it has been demonstrated that in some people 
infected with HIV , the initial manifestations of AIDS are accompa-
nied by some forms of mental disorder, such as mood disorders or dementia.
(4) The prevention of these forms of mental disorders 
follow the same measures as for the prevention of AIDS in general. However, it is not yet certain if the newer combined treatments (bi- and tritherapy) can alter the course of AIDS when brain damage due to HIV has been conﬁ  rmed.
(b) Intellectual disorder (mental retardation)
Up to 15 per cent of cases of intellectual disorder could be prevented 
by dealing with the causes that lead to it. A recent WHO publi-cation

(2) has set detailed guidelines for the prevention of some 
forms of this condition, namely, Down syndrome, foetal alcohol syndrome, phenylketonuria, and iodine deficiency syndrome. 7.4 primary prevention of mental disorders

SECTION 7  social psychiatry and service provision 1448
These preventive actions are both efﬁ  cient and affordable even in 
very poor regions of the world.
◆ Down syndrome —The primary prevention of Down syndrome 
can be successfully achieved through the control of the age at 
which women become pregnant: ideally, the age range during 
which the risk is minimal is between 16 and 35 years, after which 
the risk increases almost exponentially, as shown in Fig. 7.4.1. 
Amniocentesis is a procedure that can be very useful for the 
in utero  diagnosis of Down syndrome (as well as of other prob-
lems and malformations). Where it is culturally and morally 
acceptable, and legally permitted, a therapeutic abortion is 
viewed by some as another primary prevention measure.
◆ Iodine deﬁ  ciency —The world population at risk of intellectual 
disability due to iodine deﬁ  ciency is approximately 1 billion and 
it still occurs in large numbers in some regions of the globe.(6)

However, it can be very efﬁ  ciently and cheaply prevented through 
the addition of iodine to salt, milk, ﬂ  our, or water, or, in special 
situations, through injections of an oily solution containing 
iodine.(7)
◆ Phenylketonuria —Intellectual disorder due to phenylketonuria 
can also be successfully prevented through the early identiﬁ  ca-
tion of children at risk who then receive a phenylalanine-free diet 
throughout their lives.(8)
◆ Foetal alcohol syndrome  (FAS)—Intellectual disorder and mal-
formations seen in FAS syndrome can be prevented if women 
stay away from alcohol during pregnancy, more particularly dur-
ing the ﬁ  rst trimester, or at least keep their alcohol intake below 
the dangerous limit of 15 g of ethanol per day.(9)
Table 7.4.1 summarizes actions which can effectively prevent

Table 7.4.1 summarizes actions which can effectively prevent 
some forms of intellectual disorder. Prevention of intellectual dis-
order is discussed further in Chapter 10.3.
Mental disorders without a well-established aetiology 
but with a relatively predictable course
In this group of disorders, the target for prevention is not the 
disorder itself, whose aetiology is not clearly established, but the occurrence of further episodes of the disorder, since these are 
chronic recurrent disorders. Three good examples of this are mood 
disorders, schizophrenia, and alcohol dependence syndrome.
(a) Mood disorders
In addition to the use of antidepressants and neuroleptics to treat 
episodes of depression and mania, respectively, it has been demon-
strated that the appropriate use of lithium salts can prevent the

strated that the appropriate use of lithium salts can prevent the 
reappearance of new episodes of disease, or at least increase the 
disease-free periods and reduce both their duration and severity. 
The use of lithium salts, also called psychoprophylactics, is now 
a standard procedure for the treatment and management of mood 
disorders and this use can be considered as a form of prevention of 
mood disorders (see Chapter 4.5.8).
(b) Schizophrenia
Although no evidence of a deﬁ  nite cause of schizophrenia is yet 
available, it can be reasonably controlled through the use of psy-
chopharmacotherapy and psychosocial interventions. Relapse rates 
(measured by number of hospital readmissions or days in hospital) 
decrease signiﬁ  cantly when persons with schizophrenia adhere to 
some speciﬁ  c pharmacological regimens and are exposed, together 
with their relatives, to psychoeducational programmes.(10) These

with their relatives, to psychoeducational programmes.(10) These 
usually include some social skills training for the patient and infor-
mation about the disease and the management of expressed 
emotions for the relatives. Unfortunately, schizophrenia is a very 
long-lasting condition, even lifelong, and most studies on the 
combination of those two approaches have not yet gone beyond a 
follow-up of 48 months, thus limiting the full appreciation of its 
long-term efﬁ  ciency.
This term refers to both the alcohol dependence syndrome and 
other forms of problematic use of alcohol. For people in either 
category, whenever total abstinence is an unachievable or undesir-
able goal, the intake reduction, particularly when in connection 
with risk or dangerous situations, may become the target for

with risk or dangerous situations, may become the target for 
prevention. There are several therapeutic techniques usually 
revolving around brief interventions that are useful to help people 
signiﬁ  cantly to reduce their alcohol and their exposure to problems Fig. 7.4.1 Estimated risk of Down syndrome by related age. (Data from 
Gottesman.(5) Taken from the contribution of genetic factors to the common 
psychopathologies © World Health Organization, www.who.int )
Table 7.4.1  Action to prevent mental retardation
Condition Preventive action
Iodine deﬁ  ciency 
disordersIodize salt or water supply
Treat individuals at risk with iodized oil or Lugol’s solution
Down syndrome Discourage pregnancies in women over the age of 
35 years
If appropriate, provide amniocentesis to women over the 
age of 35 years
Foetal alcohol

35 years
Foetal alcohol 
syndromeUse simple screening test to identify women at risk
Discourage women from drinking alcohol during 
pregnancy
Alert women that drinking around the time of 
conception increases the risk to the child
Phenylketonuria Screen all newborn babies for phenylketonuria
Treat with a special low-phenylalanine diet
Discourage pregnancies in women with phenylketonuria

1449
associated with it (harm reduction). One should neither forget nor 
minimize the positive impact of self-help groups (such as Alcoholics Anonymous) in helping some people to achieve sobriety.
Psychosocial problems strongly associated with 
(a) Violent behaviour
In this category, the immediate target condition is not strictly a 
mental disorder. However, its close connections with some forms of mental disorder or symptoms make their prevention of immedi-ate concern in the mental health ﬁ  eld. Domestic violence (spouse 
and child beating) is strongly associated with substance abuse;
(11)
some types of mental disorders are potent risk factors for suicide (see below), and stress and anxiety are at the roots of the burnout syndrome seen in health workers (see below).
Extremely violent behaviour (and crime) is not associated with 
severe mental disorders (such as schizophrenia) as usually por-trayed by the media.
(12, 13)  On the contrary, it is more frequently

(12, 13)  On the contrary, it is more frequently 
associated with some types of personality disorders (e.g. antisocial, poor impulse control, aggressive) and with substance use, of which the most prevalent is alcohol. Hence, the control of substance use disorders (in itself a case of secondary prevention) can be seen as an example of primary prevention of domestic violence. The focus of prevention should be broadened from the individual perspective (the substance user) to the social group (the family) which is not exposed to the direct organic effects of alcohol, but nonetheless suffers from its indirect effects.
(b) Suicide
Despite the long-standing sociological tradition of considering suicide as a phenomenon associated with the social condition known as anomia,
(14) the medical profession tends to see it pri-

marily as a medical problem. Probably both are right. Among the demonstrated risk factors for suicide there are both social factors (anomy, old age, masculine gender, social isolation) and medical problems (chronic, painful, and incurable diseases and, most of all, psychiatric disorders and psychological problems). Several European studies have indicated that approximately 80 per cent of all cases of suicide are associated with alcohol use and depression combined.
(2) This indicates the appropriateness of targeting the 
treatment of these two conditions (another secondary prevention intervention) regarding the prevention of suicide. However, given the broad social implications of suicide, treatment of mental disorders alone has not yet produced a signiﬁ  cant reduction of 
suicide rates.

Hence the importance of a paradigmatic change which views 
suicide on a ecological perspective that considers the suicidal act as the immediate target for prevention and not just suicidal intention or ideation as subsumed by the traditional medical (and psychiat-ric) model.
(2) It is now ﬁ  rmly established that the control of the 
availability of means to commit suicide can greatly contribute to the reduction of mortality rates from suicide. According to WHO,
(2)
steps to prevent suicide can be taken in the following areas:
◆ psychiatric treatment
◆ gun control
◆ gas detoxiﬁ  cation
◆ control of toxic substances◆ responsible media reporting.
Corresponding actions to prevent suicide include:
◆ identiﬁ  cation and treatment of people suffering from depression
◆ restriction of access to guns
◆ detoxiﬁ  cation of domestic gas and car emissions
◆ controlling the availability of toxic substances and medicines
◆ downtoning reports of suicide in the media

◆ erection of physical barriers to deter jumping from high places.
A more detailed discussion about the prevention of suicide can 
be found in Chapter 4.15.4.
(c) Staff burnout
Freudenberger(15) ﬁ rst used the term ‘staff burnout’ to describe a 
‘syndrome of exhaustion, disillusionment and withdrawal in vol-untary mental health workers’ . The concept has aroused consider-able interest in the caring professions, and the publication of a large number of articles and books on the subject suggests that burnout is a major problem in health services.
(2)
Indeed, with the general trend towards community-based care in 
many parts of the world, burnout is now a problem faced by all caregivers, including the relatives of people suffering from chronic disorders.

There is no single accepted deﬁ  nition of burnout; however, there 
is general agreement that the syndrome has three major character-istics, which are observed in various caregivers, particularly health workers and family members:
◆ emotional exhaustion
◆ depersonalization
◆ a reduced feeling of personal accomplishment.
The two approaches most frequently employed to prevent staff 
burnout are:
◆ Stress management (at the individual level);(16) and
◆ Supervisor training (at the organizational level).(17)
Table 7.4.2 summarizes actions which contribute to the 
prevention of burnout among health care staff, at different levels of intervention.
Who is responsible for primary prevention?

As indicated in the introduction of this section, one of the obstacles to a greater involvement of mental health professionals in preven-tive action stems from the fact that the effective actions for the 
Table 7.4.2  Action to prevent staff burnout
Avoid making unrealistically high demands of caregivers
Ensure that all workers have some rewarding tasksTrain caregivers in time-management and relaxation techniquesModify jobs that are proving too stressful
Encourage the formation of support groups
Consider the possibility of part-time employmentEncourage workers to participate in decisions which affect them7.4 primary prevention of mental disorders

SECTION 7  social psychiatry and service provision 1450
prevention of several mental disorders often falls outside their 
usual remit and in many cases falls outside the health sector altogether, as indicated in Table 7.4.3. Although this is true, it does not mean that mental health professionals do not have a major role to play in three areas: advocacy, information generation, and 
supervision.
Perhaps mental health professionals need to reconsider their 
potential role in primary prevention; for instance, they could develop their potential to act as advocates and advisers to professionals in other sectors. As Eisenberg
(18) has argued:
what matters is not the mode of action of the agent, the venue in which it is applied, or the academic discipline of the practitioner, but the effectiveness of the measure in preventing diseases manifested by disturbances in mental function.

At any rate, prevention is unquestionably a public health priority. Accordingly, WHO has recently published a book on this aspect of prevention, whose reading is strongly recommended.
Bertolote, J.M. (ed.) (1965). Primary prevention of mental, neurological and 
psychosocial disorders . World Health Organization, Geneva.
Leavell, H.R. and Clark, E.G. (1965). Preventive medicine for the doctor in 
his community: an epidemiological approach  (3rd edn). McGraw-Hill, 
New Y ork.
World Health Organization. (2004). Prevention of mental disorders: 
effective interventions and policy options . World Health Organization, 
Geneva.
 1. Leavell, H.R. and Clark, E.G. (1965). Preventive medicine for the doctor 
in his community: an epidemiological approach  (3rd edn). McGraw Hill, 
New Y ork.
 2. Bertolote, J.M. (ed.) (1998). Primary prevention of mental, neurological 
and psychosocial disorders . World Health Organization, Geneva.

New Y ork.
 3. Schneck, J.M. (1960). A history of psychiatry . C.C. Thomas, 
Springﬁ  eld, IL.
 4. Maj, M. (1990). Psychiatric aspects of HIV-1 infection and AIDS. 
Psychological Medicine ,20, 547–63.
 5. Gottesman, I. (1982). The contribution of genetic factors to the common 
psychopathologies . World Health Organization, Geneva.
 6. Hetzel, B.S. (1986). Mental defect due to iodine deﬁ  ciency: a major 
international public health problem that can be eradicated. In Science and service in mental retardation  (ed. J.M. Berg), pp. 297–306. 
Methuen, London.
 7. Dunn, J.T. and van der Haar, F. (1990). A practical guide to the correction 
of iodine deﬁ  ciency . International Council for Control of Iodine 
Deﬁ ciency Disorders, Adelaide.
 8. World Health Organization. (1985). Community approaches to the

 8. World Health Organization. (1985). Community approaches to the 
control of hereditary diseases :report of a WHO advisory group .
 9. Smith, I.E., Lancaster, J.S., Moss-Wells, S., et al.  (1987). Identifying 
high-risk pregnant drinkers: biological and behavioural correlates of continuous heavy drinking during pregnancy. Journal of Studies on 
Alcohol ,48, 304–9.
10. Leff, J. and Waughn, R. (1981). The role of maintenance therapy 
and relative expressed emotion in relapse of schizophrenia: a 2-year follow up. The British Journal of Psychiatry ,139, 102–4.
11. Regier, D.A., Farmer, M.E., Rae, D.S., et al. (1990). Comorbidity of 
mental disorders with alcohol and other drug abuse: results from 
the Epidemiological Catchment Area (ECA) study. The Journal of the 
American Medical Association ,264, 2511–18.

12. Barbato, A. (1998). Psychiatry in transition: outcomes of mental 
health policy shift in Italy. The Australian and New Zealand Journal of 
Psychiatry ,32, 673–9.Table 7.4.3  Agents for prevention
Condition Effective agents for prevention
Down syndrome Family planning professionals
Obstetricians/midwivesWomen’s associations
Foetal alcohol syndrome General health-care personnel
Substance abuse professionals
Family planning professionalsObstetrictans/midwives .EducatorsWomen’s associations
Phenylketonuria Obstetricians/midwives
PaediatriciansNutritionists
Iodine deﬁ  ciency General health-care personnel
NutritionistsGroups involved in salt production/tradeWater supply personnelEducators
Depression Mental health workers
Rehabilitation ofﬁ  cers
Schizophrenia Mental health workers

Alcohol dependence 
syndromeGeneral health workers
Mental health workers
Self-help groups
Violence General health workers
Mental health workersPaediatriciansJustice ofﬁ  cersPolice ofﬁ  cers
Suicide Mental health workers
General health workersAgricultural and environment authoritiesJournalists
Pharmaceutical industry
Car industryTrafﬁ  c authoritiesAuthorities in charge of provision of domestic gasGun control authorities (including legislators)
Burnout Occupational health workers
General health workersStaff counsellors
Trade unions
Staff associationsPersonnel ofﬁ  cersJob supervisorsSelf-help groups

1451
13. Aldige, H.V . (1992). Civil commitment and arrests: an investigation of 
the criminalization thesis. The Journal of Nervous and Mental Disease ,
180, 184–91.
14. Durkheim, E. (1990). Le suicide . Presse Universitaire de France, 
Paris.
15. Freudenberger, H.J. (1974). Staff burn out. Journal of Social Sciences ,
30, 159–65.16. Meichenbaum, D. and Jaremko, M.E. (1983). Stress reduction and 
prevention . Plenum Press, New Y ork.
17. Kilburg, R.C., Nathan, P .E., and Thoreson, R.W. (eds.) (1986). 
Professionals in distress: issues, syndrome and solutions in psychology .
American Psychological Association, Washington, DC.7.4 primary prevention of mental disorders

7.5
Planning and providing 
mental health services for a community
Tom Burns
The aim of this chapter is to assist clinicians and managers review 
and plan services effectively for their local population. Severe psychiatric disorders manifest themselves in social relations and often disrupt social structures; they have wide-ranging conse-quences and services need to be comprehensive. Health and social care have been intertwined in psychiatry from its origins—it is neither feasible nor sensible to ignore the wider context of their management.
Mental health services research
The last 30 years have seen an explosion of Mental Health Services Research alongside the shrinking and closure of mental hospitals (see Chapter 7.6). Policy considerations, particularly cost contain-ment and public safety, have inﬂ  uenced the research agenda which

is disproportionately Anglophone (from the United States, United Kingdom, and Australasia) and focused on new services developed as alternatives to institutional care with stafﬁ  ng and motivation 
that are not easily generalizable. More routine practices, crucial for safe and effective care, have been relatively neglected by researchers.
Scope of chapter
This chapter is mainly devoted to describing the essential compo-nents of a mental health service—its ‘building blocks’ . It will then consider how they relate to one another, how they can be priori-tized, and how integrated into an effective local service linking into other essential services. Lastly it will stress how their inevitable evolution should be monitored.
Services for adults (increasingly referred to as ‘adults of working

Services for adults (increasingly referred to as ‘adults of working 
age’ indicating 18–65 years) will be used as the template. In many settings these may be the only services, stretching to accommodate all comers. In better resourced health care systems a range of specialized services have evolved from this basic model and are described elsewhere in this section (refugees 7.10.1, homeless 7.10.2, and ethnic minorities 7.10.3).Building blocks of mental health services: 
care and treatment
Most mental health treatments (whether psychological, pharmaco-
logical, or social) are based on face-to-face interviews and do not require sophisticated equipment or buildings. Institutions (the asylums) evolved for social care of disabled individuals, to protect them while they recovered and, sometimes, to protect society from them. Patients needing long-term institutional care are now rela-tively few but psychiatry is judged on how they are managed and service planners must pay them due attention.

Inpatient beds
No comprehensive service can survive without access to 24 h nurs-ing supervision for acute episodes of severe illness. These include patients at risk from neglect or suicide or those lacking insight. Wards usually accommodate 10–20 patients. It is rarely possible to effectively staff and run stand-alone units of less than 3–4 such wards (30–60 beds). Ward size is a trade-off between privacy and domesticity against effective supervision. Single rooms are prefer-able, affording maximal privacy and, while initially expensive, improve ﬂ  exibility and reduce conﬂ  ict.
Smaller, more ﬂ  exible, units such as ‘crisis houses’ offering 24 h 
care are a useful complement to inpatient wards, but not a replace-ment. Ward design and management are increasingly crucial as improved community care concentrates involuntary and disturbed inpatients in them.
How many acute beds?

‘How many beds do we need for our local population?’ is often the ﬁ rst question asked by planners or managers. Unfortunately there 
is no reliable or precise answer to this. We know that supply will drive use (perceived as need)—beds are rarely left unﬁ  lled despite 
enormous variation in their availability. It is also surprisingly difﬁ  -
cult to collect useable ﬁ  gures on bed usage nationally or inter-
nationally because of differences in methods of reporting and also the profusion of overlapping and rarely deﬁ  ned local terms

1453
(e.g. night hospitals, crisis homes, step-down wards). The levels of 
external accommodation provision (e.g. hostels, day care) clearly 
also impact the need for acute beds. Similarly need for beds will reduce as community services become more comprehensive and robust.
European provision of general acute beds in 2000 in the public 
sector ranged from 128 per 100 000 in the Netherlands to 6 per 100 000 in Northern Italy. However, unless we know the pattern of care (in particular the level of private and social services care) these ﬁ gures tell us relatively little. The United Kingdom has little parallel 
private care and here acute beds needed for a population of 250 000 have been estimated to range from 50 to 150 plus 5 to 20 secure or intensive care beds
(1) dependent on morbidity (generally much 
higher in large urban settings). London ﬁ  gures for the mid-1990s

higher in large urban settings). London ﬁ  gures for the mid-1990s 
were very close to this range, averaging 73 for outer and 110 for inner London, but with increased secure provision, particularly in the deprived inner city. The authors predicted a similar range of 24 h supervised hostel need (40–150 per 250 000 population) and London use was somewhat higher (99 and 162 per 250 000, respectively) but with a markedly wider range.
Current bed usage in the United Kingdom is closer to the 50 per 
250  000 and well below this in stable communities. This reﬂ  ects 
both the establishment of specialized home-treatment and asser-tive outreach teams and the expansion of forensic care but also a shift in expectations and practice. The average duration for admis-sions has been steadily reducing over the last three decades. Figures 
can be misleading as they are heavily skewed by short (1–2 day)

can be misleading as they are heavily skewed by short (1–2 day) 
admissions but the current admission for an uncomplicated psychotic relapse is likely to be between 3 and 6 weeks.
Longer inpatient care
Acute inpatient wards admit patients for weeks or a couple of months. Rapid discharge is anticipated and regimes emphasize openness and independence. Even within a local service some patients will require longer or more secure care because of illness severity or for legal reasons. Modern rehabilitation practice restricts long-stay wards to patients whose behaviour is persistently unac-ceptable to local communities. Forensic and secure services are usually a regional or national rather than local responsibility.
Diagnosis-speciﬁ  c wards
Alcohol and substance abuse wards have been long established

Alcohol and substance abuse wards have been long established 
(especially in Scandinavia and Central Europe) and diagnosis- or disorder-specific wards are increasingly common. Wards for specialized patient groups such as anorexia nervosa or resistant schizophrenia provide highly speciﬁ  c regimes. These are generally 
an adjunct to acute admission wards rather than an alternative. Some services are organized in disorder-speciﬁ  c wards (e.g. a psy-
chosis unit, a psychosomatic ward) instead  of general wards. 
Such specialization is not possible in comprehensive services for populations of less than about 1  000  000. For smaller populations this increased specialization must be balanced against reduced ﬂ exibility and energy wasted in ‘boundary disputes’ .
Day care
Day care is provided either in day-hospitals or day-centres, with

Day care
Day care is provided either in day-hospitals or day-centres, with 
little consistency in the terms or practices. Patients attend usually from 1 to 5 days a week for a half or whole day before returning to 
their homes in the evening. It is particularly valuable when families  
are out at work but can offer support at evenings and weekends or for very isolated patients.
Generally day-hospitals are provided by health services, include 
medical and nursing staff and can offer treatments (e.g. the pre-
scription and monitoring of medication, psychotherapies). Day-
hospitals were a signiﬁ  cant feature in the move of mental health

hospitals were a signiﬁ  cant feature in the move of mental health 
services from mental hospitals to District General Hospital sites. However their role has been more uncertain since community teams have expanded and taken on much of their therapeutic role. Many services have scaled down or even closed their day-hospitals relying more on social services for day care. Day-hospitals have had a problem of isolating themselves from service needs, locked in time with a static patient group. Comprehensive services can, undoubtedly, survive well without them, so if they are to be estab-lished it is essential that there are strong links into local teams who can exercise some control over their clientele and their activity.
Day-centres, provided by social care organizations, can rarely

Day-centres, provided by social care organizations, can rarely 
provide treatments or employ clinical staff. However overlap is wide with services highly speciﬁ  c to local context (e.g. a drop-in 
day-centre may be the main provider of psychiatric assessment and treatment in areas of high social mobility and homelessness). Generally day-centres provide long-term social support and day-hospitals focused interventions and treatments.
(2) The ‘Club 
House’ is a specialized rehabilitation day centre, popularized in the United States, which emphasizes useful normal work and where members take responsibility for running the centre with minimal supervision. Many day units now function in the evening and at weekends.
Acute day-hospitals in Europe and partial hospitalization in the 
United States have been energetically proposed as alternatives to inpatient care
(3) but have had little impact. While day-hospitals 
never achieved their anticipated prominence they serve speciﬁ  c

never achieved their anticipated prominence they serve speciﬁ  c 
groups well (e.g. mothers with small children or protracted treat-ment of eating disorders or personality problems). Day care is problematic in rural settings but adaptations such as travelling day-centres (i.e. a team that moves from setting to setting on speciﬁ  c days) or a weekly open day run by the community team are 
worth considering.
Supported accommodation and 
residential care
Many patients remain well outside hospital only with adequate 
support. At its most basic this implies stable, affordable accommo-dation. For many, however, supervision is needed to ensure self care, continued medication, and to anticipate and defuse crises. This can be provided by voluntary agencies, social services, or health services. Voluntary agencies tend to be more efﬁ  cient at pro-

viding long-term residential care
(4) but they may be reluctant to 
accept risky patients (e.g. with a history of violence or substance abuse). A mixed economy works best and the need for health services supported accommodation depends on the vigour of local voluntary and social services. While some purpose built units exist, the accommodation is usually shared adapted houses to promote 
integration and reduce stigma.7.5 planning and providing mental health services for a community

SECTION 7  social psychiatry and service provision 1454
Supported or sheltered accommodation is subject to a bewilder-
ing terminology but can be considered at four basic levels of 
increasing need:
1Group homes . These have no regular staff and are reserved for 
relatively independent patients visited by staff from their own community teams.
2Day -staffed hostels . One or two staff are present each day 
to support and monitor patients (encouraging cooking and cleaning, etc). They would usually not provide speciﬁ  c treatment 
but liaise with the community team about it.
3Night-staffed hostels . Non-clinical staff sleep over in the hostel 
to provide greater safety and availability.
424 h staffed/nursed hostels . On-site clinical staff are available

424 h staffed/nursed hostels . On-site clinical staff are available 
overnight either sleeping in or, sometimes, awake. These are expensive hostels and generally restricted to patients with long-term severe illnesses (including sometimes those compulsorily detained). Night-staffed hostels tend to be larger usually with 10–20 residents as opposed to 4–8 in day staffed ones.
Most comprehensive local services provide levels 1 and 2 and 
most social services undertake to provide level 3. Level 4 is relatively rare and would usually serve a population of 500 000–1 000 000.
Ofﬁ ce-based care and outpatient clinics
In insurance-based systems many psychiatrists run individual 
ofﬁ ce practices and manage patients on their own. In state-funded

ofﬁ ce practices and manage patients on their own. In state-funded 
systems this is rare; most work in outpatient clinics or mental health teams. Both approaches should be considered when plan-ning and providing public mental health services, paying particular attention to ﬁ  nancial regulations that can inhibit integration and 
development (comprehensive planning may pose a signiﬁ  cant 
threat to their livelihood and be resisted). Ofﬁ  ce-based practice 
remains widespread but neglected in academic and policy publica-tions. It tends to be narrow in remit (usually either psychotherapy or pharmacotherapy) and is poorly equipped for managing severe disorders.
Outpatient clinics (‘polyclinics’ or ‘dispensaries’) are an essential 
part of modern services increasingly replacing ofﬁ  ce practice. 
Psychiatrists and psychologists may still operate independently

Psychiatrists and psychologists may still operate independently 
within them but with access to enhanced resources and second opinions. In the public sector outpatient clinics may operate either alongside community mental health teams (CMHTs) or as part of them (which works better for severe illness).
(5) They provide 
an efﬁ  cient, predicable format for assessments, treatment, and 
monitoring.
Community mental health centres (CMHCs)

Mental hospitals, for all their faults, had no problems coordinating care; what little was available was all in the same place. Outpatient clinics expanded to Community Mental Health Centres (CMHCs) providing a wide range of services located in shared buildings (e.g. depot clinics, a day-hospital, psychotherapy services). The failure of the early US CMHCs demonstrated that relying entirely on patients to attend fails to engage the more ill and also that down-playing the ‘medical model’ made it impossible to recruit psychiatrists, further distancing practice from the severely ill.Most CMHTs are based in CMHCs sharing accommodation

with other CMHTs and services (e.g. day care). They provide an important safeguard in sustaining clinical standards and reducing the professional isolation in dispersed community services. This is a particularly important safeguard for community teams which can otherwise easily become idiosyncratic and rigid in their practice if not forced into regular contact with others.
Multidisciplinary Community mental health 
teams (CMHTs)
Most community mental health services consist of varied forms 
of multidisciplinary CMHT consisting of psychiatrists, nurses, social workers and often psychologists, and occupational therapists. The stafﬁ  ng of these teams will vary but their strength is that

of multidisciplinary CMHT consisting of psychiatrists, nurses, social workers and often psychologists, and occupational therapists. The stafﬁ  ng of these teams will vary but their strength is that 
regular meetings to assess and review the management of patients incorporates their varied professional perspectives and allocates tasks based on skills and needs. Developed initially in France and the United Kingdom and championed latterly in Italy they have seen further specialization from North America and Australia.
The generic sector CMHT (‘The CMHT’)
Who it is for
The CMHT is the fundamental building block of modern commu-

nity mental health services. It originated as mental hospital catchment areas (often covering a whole city or county) were divided into sectors of 50–100 000 inhabitants to permit ongoing care. The aim was that it should be possible for most of the team to have some familiarity with most of its complex and long-term patients and to have some personal  knowledge of its referrers 
and community resources. Current sector size in Western Europe ranges from 20–50 000 population, determined both by resources (shrinking as investment increases) and by the local conﬁ  guration. 
As more specialized teams are established the CMHTs remit may be reduced and sector size consequently increased keeping its caseload fairly constant. 200–250 is considered the maximum for most teams to exploit multidisciplinary working. The number is less in

services for highly complex and difﬁ  cult patients.
CMHTs offer assessment and care for patients discharged from 
psychiatric units and those who cannot be adequately treated in primary care or in the private sector. They should prioritize severe mental illnesses (SMI—e.g. psychoses and severe affective disor-ders). However diagnosis is not all—complications from social adversity, personality difﬁ  culties, or substance abuse can make sec-
ondary mental health care necessary even for apparently ‘minor’ disorders. T ools to clarify this threshold
(6) have been of limited 
use and most teams rely on clinical assessments. In countries with limited private care CMHTs also treat mild and transient disorders. CMHTs can be remarkably inefﬁ  cient if little thought is given 
to their structure and thresholds. T o work well, there needs to be agreement on their purpose, clientele and systems of management and they have often suffered from lack of clarity and leadership.

Stafﬁ  ng and management
CMHT stafﬁ  ng varies enormously and there is no uniform model. 
T eams of less than 6 can rarely provide comprehensive care or 
cross-cover while teams of more than about 12–15 start to become

1455
unwieldy, overwhelmed with management and information transfer. 
CMHTs emphasize skill-sharing and a degree of generic working 
and have evolved an informal, democratic style(7) which often 
means confusion over clinical leadership (originally provided informally by senior medical staff). With increased staff numbers and treatment complexity ‘team managers’ now coordinate work-load with a role which varies from the purely administrative to setting clinical priorities and supervising staff. Establishing a clear understanding of clinical leadership in CMHTs (without inhibiting initiative and creativity) is essential for effective functioning. If leadership and management are separated (common with a strong medical presence) the roles need to be well deﬁ  ned and 
relationships good.

The key to good care is accurate assessment (see Chapter 1.8.1). Most commonly psychiatrists conduct initial assessments (usually in an outpatient clinic) and involve the team members in treat-ment. Increasingly other team members have taken a role in assess-ments, either individually or jointly with the psychiatrist. Although this issue generates strong feelings there is surprisingly little research into it. With highly developed primary care non-medical assessments may be effective but otherwise medical time should prioritize assessments. With severely ill patients home-based assess-ments pay considerable dividends.
(8, 9)
Case management
Most CMHT staff act as clinical case managers(10, 11) with responsibil-

(8, 9)
ity for coordination, delivery, and review of care for their patients. The caseloads of staff members should be explicitly limited (usually 15 to 30) and reviews recorded and systematic. In the United Kingdom this has been formalized as the Care Programme Approach.
(12)
Fig. 7.5.1 shows a care plan indicating a patient’s needs or problems, the interventions proposed to meet them, who is responsible and who is informed, plus an agreed date for review. Such concise structured paperwork (as with the risk assessment and contingency plan (Fig. 7.5.2)) can be adapted to any service, coordinates complex care and serves as a natural focus for clinical reviews. The level of detail needs to be clinically (not managerially) determined.
Team meetings

CMHTs need 1–2 regular meetings (each usually 1.5–2 h) per week for both clinical and administrative business. The degree of struc-ture depends on team style and remit.
(a) Allocation of referrals
Referrals can be allocated by who is ﬁ  rst available or by matching 
the clinical problem against available skill and training. Time dis-cussing allocations before assessment is generally unproﬁ  table and 
most well-established teams delegate the task to the manager or a 
senior clinician.
(b) Patient reviews
Reviews should be held for (i) new patients , (ii) routine monitoring ,
and (iii) discharge . Reviews can range from simply reporting the 
problem and proposed treatment in uncomplicated cases through to detailed, structured, multidisciplinary case-conferences includ-ing other services (e.g. GP , housing, child protection). New patient

reviews are an excellent opportunity for providing a broad, experienced overview, and ensuring rational and fair allocation to caseloads. Routine monitoring  is often overlooked yet probably the 
most important for team efﬁ  ciency. It should be systematic and not 
only responsive to crises and problems. It shapes and redirects treatment and identiﬁ  es patients ready for discharge. The burden 
on individual staff members is regularly monitored. Routine moni-toring is a legal requirement of the Care Programme Approach and good practice in all case management. Discharge reviews  are an 
excellent opportunity for audit and learning within the team.
(c) Managing waiting lists and caseloads
Effective CMHTs need to guarantee prompt access. Routine

Effective CMHTs need to guarantee prompt access. Routine 
assessments  should be within 2–4 weeks. Sooner is rarely produc-
tive and delays above 3 weeks result in a rapidly rising rate of failed appointments.
(13)Urgent assessments  (most psychotic episodes) 
need to be seen within a week, usually within a couple of days. Emergency assessments  are for those associated with immediate risk 
(e.g. hostile behaviour or suicidal intent) and need to be seen the same day.
A practical approach to waiting lists is to count the assessments in 
the preceding year and allocate routine appointments for 20 per cent more. Thus a team with 400 assessments the preceding year allocating nine slots a week will have one available weekly for emergencies. Rapid routine assessment reduces pressure for urgent and emergency referrals more efﬁ  ciently than emergency rotas.
Communication and liaison

T eam meetings ensure internal communication but CMHTs need 
good links with a wide network of professional colleagues. Structured liaison is advisable with primary care and general hospitals in addition to routine letters. Hospital links may be between speciﬁ  c CMHTs and wards or CMHTs may provide input 
to patients from their sectors in the absence of dedicated liaison psychiatry services.
(a) General practice liaison
Much of mental health care is delivered in primary care (see Chapter 7.8) and effective coordination is essential. GP liaison systems range from informal contact through to shared care and co-location of CMHTs in GP Health Centres.
(14) An effective 
system comprises regular, timetabled meetings between the two teams or a ‘link’ CMHT member attending the GP health centre. Monthly meetings where shared and complex patients are dis-cussed are highly time-efﬁ  cient because of prompt problem solving

and crisis anticipation. However it is important to be clear about responsibilities, fudging boundaries is risky.
(b) Liaison with other agencies
The same principles apply to liaison with other agencies (social services, housing, charitable, and voluntary sector providers). Whether regular meetings are cost-effective will depend on the volume of shared work but showing up and meeting people (even just once) pays enormous dividends in improved relationships and understanding. Professional conﬁ  dentiality and information 
sharing is more sensitive.
Assertive Outreach (AO) Teams
The most replicated and researched specialist CMHT is the AO T eam. 
The original US model(9) improved clinical and social outcomes 
with substantially reduced hospitalization at slightly lower cost. 7.5 planning and providing mental health services for a community

SECTION 7  social psychiatry and service provision 1456
CPA REVIEW
Patient’s name: Jenny T
Address: 56 Acacia Avenue
Phone:CMHT:  West Central
Phone:
New patient: YES/NO
If NO, date of review: 20.10.07
Date of birth: 09.06.61
GP: Dr FindlayDiagnosis:
1…Major depressive disorder..… F 32 .0
F __ __.__ 2……………………………………… Phone:
You must consider the following: 1) Mental health, including indicators of relapse; 2) Physical health; 3) Medication; 4) Daytime
activity; 5) Personal care / living skills; 6) Carers, family, children and social network; 7) Forensic history; 8) Alcohol or substance misuse
9) Cultural factors; 10) Housing/finances/legal issues.
Complete a risk assessment and include : i) a crisis plan; ii) a contingency plan
Assessed needs or problem Intervention Resp.of
1. Depressed mood, apathetic and self critical 
2. Suicidal thoughts 
3. Daughter’s school problems 
4. Plan for recovery • Regular home visits, assess mental state 
• Encourage compliance with antidepressants

• Encourage compliance with antidepressants 
• Encourage activity – take to shops etc 
• Explore severity (+/- plans) at each visit 
• Support mother and husband who are scared 
of suicidal thoughts 
• Maintain links with class teacher 
• Keep family informed of her progress 
• Link with support group when mood lightens 
• Help reapply for part-time cleaning job BJ
BJ/ Cons 
BJ
BJ
Professionals involved in care: Dr Psychologist CPN OT SW Ward Nurse ACT Other
Ward Nurse ACT Other Present at planning meeting: Dr Psychologist CPN OT SW
Copy given to patient? YES/NO Copy sent to GP? YES/NO
Phone Billie Jarvis (BJ) Care co-ordinator(print):
Care co-ordinator (signature): .............................................................. Date of next review: 20.04.08. Job title: CPN Patient’s signature:………………………………  
On Supervision Register? YES/

NO Care management? YES/NO Risk history completed? YES/NO
On Supervised Discharge? YES/NO Relapse + risk plan required? YES/NO
Fig. 7.5.1 Care programme review document.

1457
AO teams (Box 7.5.1) are costly and consequently reserved for the 
most difﬁ  cult (‘hard to engage’ or ‘revolving-door’) psychotic 
patients with frequent, often dangerous, relapses and poor medi-cation compliance plus alcohol or drug abuse, signiﬁ  cant personality 
difﬁ culties, and offending behaviour.
AO emphasizes proactive outreach—visiting patients at home 
even when they are reluctant. It exploits enhanced team working with daily meetings and several members actively involved with most patients both for safety considerations and also reﬂ  ecting 
patients’ extensive needs. The culture is of very practical working (taking patients shopping, sorting out accommodation, delivering medicines daily if need be) well beyond traditional professional boundaries.
Despite strongly expressed convictions there is little evidence 
that AO teams need to slavishly follow the original model
(15, 16)  and local clinical adjustments are both sensible and justiﬁ  ed. If embed-

ded in a comprehensive system there is little need for a 24 h service, most staff establish strong individual relationships with patients and caseloads are usually more than the recommended 1:10. Where CMHTs function well AO teams take only patients who cannot be stabilized despite their support.
If CMHTs provide outreach and a comprehensive treatment 
then the extra AO resources may add little. Improved outcomes fol-low only from additional effective treatments (e.g. daily Clozapine visits in resistant schizophrenia); it is not outreach itself that is therapeutic. Whether AO will improve care (and, if so, how many teams are needed for how many patients) will depend on current services.
Ethics in community mental health care

Balancing patients’ welfare with their autonomy and their rights with those of their families and the wider community are sharply revealed in AO teams. These teams regularly visit patients who vigorously and clearly reject them. When does intensive support become intrusion? When does professional persistence tip over into coercion or disrespect?
Compulsion was traditionally identiﬁ  ed with the buildings of 
the old asylums or left to the family (as it still is in many parts of the world). With expanded community care, compulsion, and coercion (either explicitly in the form of legal requirements or informally through professional or social pressure
(17)) are now

(17)) are now 
a pervasive feature of practice. Improved legal and professional scrutiny makes compulsory treatment possible in the community. Most developed countries have enacted forms of community treatment order (‘mandated community treatment’ , ‘outpatient committal’) mainly for the care of young psychotic individuals CONFIDENTIAL: RELAPSE AND RISK MANAGEMENT PLAN
Name : Alastair W 
Categories of Risk Identified: 
Aggression and violence YES/NO Severe self-neglect             YES/NO
Exploitation (self or others) YES/NO Risk to children & young adults            YES/NOSuicide and self-harm  YES/NO
Other (please specify} ………………………. 
Current factors which suggest there is significant apparent risk: 
(For example: alcohol or substance misuse; specific threats; suicidal ideation; violent fantasies; anger; 
suspiciousness; persecutory beliefs; paranoid feelings or ideas about particular people)

suspiciousness; persecutory beliefs; paranoid feelings or ideas about particular people) 
Continued excessive drinking—especially when depressed. Makes him more suspicious and hostile. 
Clear statement of anticipated risk(s): 
(Who is at risk; how immediate is that risk; how severe; how ongoing) 
Clear risk to strangers (not family or staff), usually in bars. Often when poor medication compliance. 
Action Plan: 
(Including names of people responsible for each action and steps to be taken if plan breaks down) 
Relapse plan discussed and agreed—to increase antipsychotics and contact when concerned with 
people plotting (‘to help you cope with them’). 
If he feels seriously threatened to seek admission through the emergency room 
Date Completed: xx/xx/xx  Review date: xx/xx/xx
Fig. 7.5.2 Risk assessment and contingency plan.
Box 7.5.1 ACT core components
◆ Assertive follow-up.

◆ Small caseloads (1:10–1:15).
◆ Regular (daily) team meetings.
◆ Frequent contact (weekly to daily).
◆In vivo practice  (treatment in home and neighbourhood).
◆ Emphasis on engagement and medication.
◆ Support for family and carers.
◆ Provision of services using all team members.
◆ Crisis stabilization 24 h a day, 7 days a week.7.5 planning and providing mental health services for a community

SECTION 7  social psychiatry and service provision 1458
without insight into their need for ongoing treatment. The intro-
duction of these provisions has generally been controversial but their operation not so.
Community treatment orders have the advantage of legal scrutiny 
unlike most of the ethical dilemmas facing CMHT and AO staff in their day-to-day work. These require discussion case-by-case. How proper is it to inform neighbours if a patient may pose a risk to them but will not give consent? Is it right for a patient, heavily dependent on his parents, to deny them information on his treat-ment? What does a case manager do when they know their client is doing something illegal? Most professionals share the goal of maxi-mizing their patient’s autonomy while minimizing signiﬁ  cant risks. 
Guidelines exist only for extreme circumstances. T eams should be encouraged in regular discussion of these issues.
Crisis teams

Crisis teams play a crucial role where local services are poorly developed (they may be the only community services) or in city 
centres with many transient and homeless patients. They must pri-oritize rapid response and accessibility. Most teams will see patients immediately, certainly the same day. Their clinical aims and staff-ing are essentially similar to the acute functioning in CMHTs. They are best located alongside CMHTs or in the emergency rooms of general hospitals with 24 h availability. Liaison services (see Chapter 5.7) can often incorporate and manage hospital-based crisis teams.
Crisis Resolution/Home Treatment (CR/HT) Teams
The CR/HT team model, developed in Australia(18) and currently 
implemented in the United Kingdom and Europe, reﬂ  ects increased

implemented in the United Kingdom and Europe, reﬂ  ects increased 
consumer demand for access in crises and a desire to reduce inpatient care costs. It draws heavily on AO practice with limited, shared caseloads, ﬂ  exible working, extended access, and an empha-
sis on outreach. Reduction in hospitalization offsets much of their cost
(19) but this needs to be considerable as with two daily shifts 
and on call overnight needs a staff of about 15 for a caseload of 30 proposed for a population of 150 000.
(20) They target patients

(20) They target patients 
who would otherwise be in hospital and focus on the severely men-tally ill with intensive visiting (usually daily for a limited period) and considerable practical support and work with patients’ social networks; most aim for a maximum of 6 weeks involvement. Such intensive team working requires highly effective communication and the teams meet daily (often twice at shift handovers). Information transfer is burdensome and liaison with CMHTs complex requiring absolute clarity on local arrangements for clinical responsibility.
Variations in practice and sustainability
The CR/HT teams may reduce the need for hospital care(18, 21)  but 
how much will vary. The UK model is precisely speciﬁ  ed (includ-

ing who it should and should not care for, Box 7.5.2) but practice varies considerably. A full 24 h service is rarely needed, an on-call facility to the emergency room and police station at night usually sufﬁ ces. Contact frequencies are generally lower, patients stay with 
the service longer than anticipated and they are inevitably referred individuals recurrently in crisis (often with alcohol and relation-ship problems) who cannot easily be refused care but would not be ‘otherwise in hospital’ . Good medical stafﬁ  ng is needed and CMHT responsibilities need to be carefully negotiated, mutually agreed 
and crystal clear if to be avoided. These realities need to be care-fully considered before deciding to establish such teams.
Crisis services may have a relatively limited lifespan
(22) but can

(22) but can 
be a very successful way to improve local access, gain familiarity with at-risk populations, and then consolidate as a more compre-hensive service. Sometimes, however, they become overwhelmed with inappropriate referrals or patients who cannot be referred on and close.
Crisis houses and respite care

Crisis houses allow admission with a minimum of formality and often with reduced supervision compared to hospitals. They are usually small (4–8 beds) in a domestic setting and take people for days, occasionally a week or two. They are favoured for vulnerable women and early intervention services. Most have one staff mem-ber sleeping in overnight and a couple on during the day with sup-port from patients’ case managers. They are very welcome for a minority of patients but do not replace inpatient care and need careful supervision to avoid becoming chaotic or blocked.
Adjunct or replacement for CMHTs?
The three teams outlined above comprise the fundamental building blocks of most community services. AO and CR/HT teams have been proposed as substitutes for CMHTs, particularly when there are problems with local CMHTs. However both experience and research evidence
(23) suggests that they are rarely durable without

(23) suggests that they are rarely durable without 
effective CMHTs to relate to. They should be considered to improve the quality of care in otherwise well-functioning services rather than cost-saving shortcuts.
Highly specialized and diagnosis-speciﬁ  c 
teams
There are various specialized teams, generally organized on a 
regional  level. These are not essential local services but impact on Box 7.5.2 Remit of UK Crisis Resolution/Home Treatment 
Teams(20)
‘Commonly adults (16 to 65 years old) with severe mental illness 
(schizophrenia, manic depressive disorders, severe depressive disorder) with an acute psychiatric crisis of such severity that, without the involvement of the CR/HT team hospitalisation would be necessary’.
‘The service is not usually appropriate for individuals with :
◆Mild anxiety disorders .
◆Primary diagnosis of alcohol or other substance abuse .
◆Brain damage or other organic disorders including dementia .
◆Learning disabilities .

◆Exclusive diagnosis of personality disorder .
◆Recent history of self harm but not suffering from a psychotic or 
serious depressive illness .
◆Crisis related solely to relationship issues’ .

1459
them—both in terms of removing some of the clinical obligations 
and the need to ensure clear and negotiable thresholds.
Early Intervention Teams (EIS)
Concern that a long duration of untreated psychosis (DUP) con-fers poorer prognosis
(24) has led to the development of EIS teams 
which many would now argue should be standard provision. Developed mainly from Australian and UK models
(25, 26) they vary 
remarkably even despite a detailed prescription for UK teams. Some down-play diagnosis in favour of easy access, others restrict to schizophrenia, some emphasize a ‘youth service’ while others take all ﬁ  rst episode patients irrespective of age.
(7) Even more 
confusing there are three quite different activities which may, or may not, be part of the service (Box 7.5.3).
The core of EIS is a specialized CMHT which case-manages 
ﬁ rst episode psychosis patients protecting social networks and

ﬁ rst episode psychosis patients protecting social networks and 
functioning (keeping patients at college or work, an emphasis on family interventions, etc.) assuming a return to premorbid functioning. Crisis and respite houses are preferred to hospital. Some EIS teams conduct public awareness campaigns, lecturing in schools and colleges.
(27) A minority of research teams attempt to 
identify and treat ‘ultra-high risk’ patients to prevent progression to psychosis.
(28)
Forensic and rehabilitation teams
Community-focused services face particular difﬁ  culties in treatment-
resistant patients, particularly those with socially unacceptable or offending behaviour. Such patients ﬁ  t poorly into open wards and

resistant patients, particularly those with socially unacceptable or offending behaviour. Such patients ﬁ  t poorly into open wards and 
specialized forensic teams provide care where offending behaviour and danger to others predominates. Some provide community services (intensive case management of dangerous patients) with an emphasis on risk assessment and management. Integrating them with general services can be problematical.
A signiﬁ  cant number of patients remain disabled despite best 
treatments and require long-term management of disability rather than episode-based care. Rehabilitation teams generally serve patients who cannot survive without supervised accommodation even when at their best. They include the diminishing cohort of old long-stay patients and increasingly a very disturbed ‘new long-stay’ population with comorbid substance abuse and behavioural disturbances.
Diagnostic-speciﬁ  c teams
Highly specialized teams for individual disorders (e.g. eating

Highly specialized teams for individual disorders (e.g. eating 
disorders, personality disorders, bipolar patients) concentrate speciﬁ  c skills and provide specialized treatments and are usually provided at regional level. They usually have stronger advocates 
than CMHTs, both from professionals and families of sufferers, and the opportunity costs (see below) of establishing them need careful thought.
Planning services
Step-wise planning and adaptation
Planning mental health services for a given community rarely starts with a clean sheet. In such circumstances there are excellent texts, both general and specific to mental health. Tansella and Thornicroft’s ‘matrix’ model
(29) is particularly thorough and

(29) is particularly thorough and 
structured (see Chapter 7.2). It covers the process from establishing service principles and needs assessment (at national, regional, and local levels) through to monitoring and reviewing the cycle of planning and provision. They propose a hierarchical approach depending on the level of mental health spend.
(30) Case identiﬁ  ca-
tion and outpatient treatments in primary care are the priority for low income countries and only with increased resources the establishment of a secondary care mental health service (usually a form of generic CMHT). Not until these are well-established are specialist and inpatient services indicated. This process must, however, take account of what is already in place.
Local population needs assessment

Psychiatric morbidity varies considerably with social deprivation and is much higher in cities than in stable rural or suburban settings (see Chapter 2.7). At the regional and national level comparative need can be predicted fairly well from established indexes incorpo-rating levels of migrants, overcrowding, poverty, etc. Catchment areas should broadly reﬂ  ect these differences. At the more local 
level these ﬁ  gures are of limited value. How does one factor in 
travelling time or known differences in the quality of primary care? A process of negotiation is best to agree local allocation following these general guidelines. However a concentration of hostels for the mentally ill or homeless or the presence of a railway station or international airport may swamp these differences. These should 
be provisionally estimated in planning but then regularly monitored 
and reviewed.
Opportunity costs and unintended consequences

Planning mental health services has become based on international evidence, often including cost-effectiveness analyses, i.e. is there more overall patient health gain for the same input (see Chapter 7.7)? However these rarely address the opportunity costs across a whole system. For example one form of day hospital may be more cost-effective for its patients than another day hospi-tal, but is diverting nurses from an inpatient unit to staff that day hospital a net gain? Rigorous intervention studies of large systems are formidably difﬁ  cult to conduct and even more so to 
interpret.
The impact of enthusiasm and the migration of the best staff 
to such research services can be especially misleading.
(31) Successful 
new services are always reported but there is less consistency in report-ing when a service may have lost its efﬁ  cacy or was abandoned.

(5, 22)
It is best to visit examples of services that are proposed and not to 
always assume that what works for them will necessarily workfor you.
(15)Box 7.5.3 Components of early intervention teams
◆Case management —ongoing care of identiﬁ  ed patients
◆Early Identification —awareness-raising campaigns for 
psychoses
◆High risk and prodromal  patient identiﬁ  cation and treatment7.5 planning and providing mental health services for a community

SECTION 7  social psychiatry and service provision 1460
Manpower is often as signiﬁ  cant a resource limitation as fund-
ing, hence the need for a system-wide appraisal. Also, though expressed as costs, these decisions include wider judgements of values and expectations rather than simply outcomes.
(30) Local and 
national objectives also matter, not just clinical ones (e.g. public safety now dominates much mental health planning).
Cultures and funding
Health care cultures, their structures and their funding systems vary enormously. Services must be congruent with them otherwise they will not survive. Occasionally service planners can inﬂ  uence the system but more often have to adapt to it.

Obtaining relatively small changes in funding arrangements (or external governance) can deliver quite major improvements. However caution is needed as unintended consequences and perverse incentives may arise. Enthusiastic clinicians are often blind to the risks of over-prescription which can lock in outmoded practices (e.g. a highly speciﬁ  c form of day hospital or crisis 
facility) that after opening is found not to have the level of need predicted but may be so rigidly prescribed that it cannot be adapted.
How ‘integrated’ mental health care should be is a highly local 
decision. Well-established systems often strive for integration with 
general medicine or, increasingly, with social services to reduce both discrimination and administrative barriers to integrated care. For less conﬁ  dent services the value of a distinct, separate, identity

can be considerable—not least the ability to protect its resources. The 19th century British mental health reformer Lord Shaftsbury wrestled with the same dilemma.
The task of integration is easily underestimated, particularly the 
energies required to accommodate contrasting health and social care cultures. Social care, for example, tends to rely on very detailed paperwork and a highly structured system of intensive supervision (reﬂ ecting political accountability and previously only minimally 
trained workforce) as opposed to the high levels of professional autonomy in health care. Agreed compromises need to be reached before integration and the negotiations can be exhausting, but preferable to misunderstandings. The costs and beneﬁ  ts will depend 
very much on the local situation, relationships and history and should be very carefully weighed up.
Relationships with the voluntary sector and 
patients movement
Relations with local non-health statutory services (housing, educa-

tion, police) and with the voluntary sector will determine much of the success of MH services. Voluntary and private sectors may ﬁ  ll 
specialist niches left by a monolithic public health care system (as with the NHS in the United Kingdom) or conversely the public sys-tem may act as a safety net, for charitable and private provision. Service planners need to exploit the strengths of local providers. Non-statutory services are often more efﬁ  cient but less compre-
hensive and may also be less reliable over the long-term. Both may be equally reliant on public funding, differing only in contracts and degrees of independence. Patient and carer advocacy and support organizations are now a major force; effective working with them signiﬁ  cantly will enhance both the design and delivery of services 
(see Chapter 7.9).Monitoring and review

Careful monitoring and review are as important as careful planning 
for several reasons. The long-term, ﬂ  uctuating nature of disorders, 
the subjective nature of diagnoses (increasingly self-ascribed) complicate outcome measures and the targeting of services; ser-vices can easily drift to those who demand them from those who most need them; treatments (particularly psychological and psychotherapeutic treatments) may evolve over time losing their effective characteristics; needy patients are rarely demanding or well-informed; engaging and motivating them to collaborate in long-term, treatments is difﬁ  cult.
A consistent effort to deliver even the most basic, proven inter-
ventions will make a substantial difference to patient welfare. The PORT study in the United States demonstrated how schizophrenia care was strikingly inconsistent and fell below accepted essen-tials.
(32) Regular audit ensures that services remain targeted on

(32) Regular audit ensures that services remain targeted on 
those for whom they were developed and that their application and quality remains good. Monitoring can vary in sophistication—from a simple head count of who is getting what through to careful evaluation of care pathways. The audit review process feeds back into the development process, adjusting and reﬁ  ning it. Even 
in the most hard-pressed services audit more than rewards its investment.
Routine outcome measures (ROM)
Audit brings rigour and reﬂ  ection (often lost in the immediacy of 
the therapeutic relationship) into the care process. Measurement also serves a training purpose by benchmarking interdisciplinary understandings of symptoms and outcomes. Systematic, periodic recording of patients’ clinical or social status is increasingly used in both planning and research. Structured outcomes can be generic (e.g. HoNOS
(33)) or for speciﬁ  c disorders (e.g. the Brief Psychiatric

(33)) or for speciﬁ  c disorders (e.g. the Brief Psychiatric 
Rating Scale(34)) or even locally developed. Their value lies in their 
consistency of use.
Planning and providing mental health services requires ﬂ  exibility 
and compromise. Epidemiological and service statistics translate poorly to local planning; this remains primarily a practical and political, rather than academic, activity. The scientiﬁ  c evidence is 
dominated by Anglophone alternatives to hospital care studies but local history, culture, mental health law, and political imperatives cannot be ignored. Mediterranean societies, for example, with strong family supports and fewer isolated psychotic individuals have less interest in AO teams. A high-proﬁ  le patient homicide, or 
a strong public endorsement of services by politician or celebrity, can derail years of careful planning.
This chapter has attempted to draw out some principles (Box 7.5.4)

for the process but these can only be guidelines. Inevitably the decision will be based on what is possible  locally. Despite this most 
solutions draw on a limited number of tried and tested structures 
described here in some detail. Their balance and conﬁ  guration 
depend on what is available for them and around them. Above all the mentally ill and their families deserve reliable and predictable services. Not all change is innovation and research ﬁ  ndings should 
be judged in terms of their sustainability and demonstrated translation from research efﬁ  cacy to clinical effectiveness.

1461
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Thornicroft, G. and Tansella, M. (1999). The mental health matrix: a manual 
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3. Marshall, M. (2003). Acute psychiatric day hospitals. British Medical 
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4. Knapp, M., Hallam, A., Beecham, J., et al.  (1999). Private, voluntary or 
public? Comparative cost-effectiveness in community mental health care. Policy and Politics ,27(1), 25–41.
5. Wright, C., Catty, J., Watt, H., et al.  (2004). A systematic 
review of home treatment services. Classiﬁ  cation and sustainability. 
Social Psychiatry and Psychiatric Epidemiology ,39, 789–96.
6. Slade, M., Powell, R., Rosen, A., et al.  (2000). Threshold assessment 
grid (TAG): the development of a valid and brief scale to assess the severity of mental illness. Social Psychiatry and Psychiatric Epidemiology ,
35(2), 78–85.
7. Burns, T. (2004). Community mental health teams . Oxford University 

8. Burns, T., Beadsmoore, A., Bhat, A.V ., et al.  (1993). A controlled trial of 
home-based acute psychiatric services. I: clinical and social outcome. The British Journal of Psychiatry ,163, 49–54.
9. Stein, L.I. and T est, M.A. (1980). Alternative to mental hospital 
treatment. I: conceptual model, treatment program, and clinical evaluation. Archives of General Psychiatry ,37(4), 
392–7.10. Intagliata, J. (1982). Improving the quality of community care for 
the chronically mentally disabled: the role of case management. Schizophrenia Bulletin ,8(4), 655–74.
11. Holloway, F., Oliver, N., Collins, E., et al. (1995). Case management: 
a critical review of the outcome literature. European Psychiatry ,
10, 113–28.
12. Department of Health. (1990). The care programme approach for

12. Department of Health. (1990). The care programme approach for 
people with a mental illness referred to the special psychiatric services. Department of Health, London. Report No.: Joint Health/Social Services Circular HC (90) 23/LASS (90) 11.
13. Burns, T., Raftery, J., Beadsmoore, A., et al. (1993). A controlled trial of 
home-based acute psychiatric services. II: treatment patterns and costs. The British Journal of Psychiatry ,163, 55–61.
14. Burns, T. and Bale, R. (1997). Establishing a mental health liaison 
attachment with primary care. Advances in Psychiatric Treatment ,
3, 219–24.
15. Fiander, M., Burns, T., McHugo, G.J., et al.  (2003). Assertive 
community treatment across the Atlantic: comparison of model ﬁ delity in the UK and USA. The British Journal of Psychiatry ,
182, 248–54.
16. Burns, T., Marshall, M., Catty, J., et al.
 (2005). Variable outcomes in

 (2005). Variable outcomes in 
case management trials—an exploration of current theories using meta-regression and meta-analysis : Final Report. Department of Health, 
London.
17. Monahan, J., Redlich, A.D., Swanson, J., et al. (2005). Use of leverage 
to improve adherence to psychiatric treatment in the community. Psychiatric Services ,56(1), 37–44.
18. Hoult, J. (1986). Community care of the acutely mentally ill. The British 
Journal of Psychiatry ,149, 137–44.
19. Smyth, M.G. and Hoult, J. (2000). The home treatment enigma. British 
Medical Journal ,320(7230), 305–9.
20. Department of Health. (2001). The mental health policy 
implementation guide. Department of Health, London.
21. Johnson, S., Nolan, F., Pilling, S., et al. (2005). Randomised 
controlled trial of acute mental health care by a crisis resolution team: the north Islington crisis study. British Medical Journal ,
331(7517), 599.

22. Cooper, J.E. (1979). Crisis admission units and emergency psychiatric 
services. Public Health in Europe, No. 2. Copenhagen: World Health Organisation.
23. Burns, T., Catty, J., Watt, H., et al.  (2002). International differences in 
home treatment for mental health problems. Results of a systematic review. The British Journal of Psychiatry ,181, 375–82.
24. Marshall, M., Lewis, S., Lockwood, A., et al.  (2005). Association 
between duration of untreated psychosis and outcome in cohorts 
of ﬁ rst-episode patients: a systematic review. Archives of General 
Psychiatry ,62(9), 975–83.
25. Edwards, J., McGorry, P .D., and Pennell, K. (2000). Models of early 
intervention in psychosis: an analysis of service approaches. In Early

intervention in psychosis: an analysis of service approaches. In Early 
intervention in psychosis: a guide to concepts, evidence and interventions(eds. M. Birchwood, D. Fowler, and C. Jackson). John Wiley & Sons, New Y ork.
26. Birchwood, M., T odd, P ., and Jackson, C. (1998). Early intervention 
in psychosis. The critical period hypothesis. The British Journal of 
Psychiatry —Supplement ,172(33), 53–9.
27. McGorry, P . and Jackson, H. (1999). Recognition and management of 
early psychosis. A preventative approach. Cambridge University Press, 
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controlled trial of interventions designed to reduce the risk of progression to ﬁ  rst-episode psychosis in a clinical sample with 
subthreshold symptoms. Archives of General Psychiatry ,59(10), 921–8.

29. Tansella, M. and Thornicroft, G. (1998). A conceptual framework 
for mental health services: the matrix model. Psychological Medicine ,
28(3), 503–8.Box 7.5.4 Developing local community mental health services
◆ Make a careful inventory of what services exist, and any special 
local needs.
◆ Consult locally and invest heavily in building coalitions with 
policy makers, statutory services, and voluntary groups.
◆ T est research evidence for durability and relevance. If possible 
visit established services and ask ‘around the service’ .
◆ Monitor and review regularly. Improved consistency of 
current practice often delivers more than introducing new treatments.
◆ Consider carefully opportunity costs. Include both the impact 
of a speciﬁ  c improvement across the whole service and the 
costs of system change itself.

◆ Avoid excessive reorganization—not all change is innovation.7.5 planning and providing mental health services for a community

SECTION 7  social psychiatry and service provision 1462
30. Thornicroft, G. and Tansella, M. (2004). Components of a modern 
mental health service: a pragmatic balance of community and hospital 
care: overview of systematic evidence. The British Journal of Psychiatry ,
31. Coid, J. (1994). Failure in community care: psychiatry’s dilemma. 
British Medical Journal ,308(6932), 805–6.
32. Lehman, A.F. and Steinwachs, D.M. (1998). Translating research 
into practice: the Schizophrenia Patient Outcomes Research T eam (PORT) treatment recommendations. Schizophrenia Bulletin ,24(1), 
1–10.
33. Orrell, M., Y ard, P ., Handysides, J., et al.  (1999). Validity and 
reliability of the health of the nation outcome scales in psychiatric patients in the community. The British Journal of Psychiatry ,174,
409–12.
34. Overall, J.E. and Gorham, D.L. (1962). The brief psychiatric rating 

7.6
Evaluation of mental 
health services
Evaluation is the basis for improving care to people with mental 
illness. It is vital to know whether interventions are beneﬁ  cial or 
harmful, and whether they offer value for money. Mental health interventions need to be understood both in terms of their active ingredients and how they ﬁ  t within their context.
(1) Such combined 
interventions, often including pharmacological, psychological, and social elements, are the epitome of ‘complex interventions’
(2) and 
their evaluation poses considerable challenges. In this chapter we shall discuss deﬁ  nitions  of evaluation, and go on to discuss why
evaluate, what  to evaluate, and how to evaluate mental health ser-
vices. In our conclusion we shall offer an indication of the most important trends in this ﬁ  eld in the coming years. The overall

vices. In our conclusion we shall offer an indication of the most important trends in this ﬁ  eld in the coming years. The overall 
approach that we take is centred upon the idea that ongoing evalu-ative research is of fundamental importance in discovering which interventions are effective, neutral, or harmful, and that such infor-mation is essential to deliver better mental health care.
Evaluation: deﬁ  nitions and conceptual 
framework
The Concise Oxford English Dictionary(3) gives the following deﬁ  ni-
tions of ‘evaluation’:evaluate  (verb transitive )1. assess, appraise; 2a. ﬁ nd or state the 
number or amount of; 2b. ﬁ nd a numerical expression for.
evaluation  (noun )1. appraisal, valuation, assessment; 2. estimate, 
estimation, approximation, rating, opinion, ranking, judgement, reckoning, ﬁ  guring, calculation, computation, determination.
The etymological root of the word therefore refers directly to

The etymological root of the word therefore refers directly to 
‘value’ , although in common usage ‘evaluation’ now has a more technical connotation. In our view evaluation necessarily requires both the precise measurement of the effects of treatments or ser-vices, alongside a contextual understand of the meaning, and value of such results.
A conceptual model that can be used to clarify key issues related 
to the evaluation of mental health services is the Matrix Model.
(4, 5)
The two dimensions  of this model are place and time (see Table 
7.6.1). Place refers to three geographical levels: (1) country/regional, (2) local, and (3) individual. Time refers to three phases: (A) inputs, (B) processes, and (C) outcomes. In this framework inputs  relates

to all those resources which are necessary before health care can take place (such as ﬁ  nancial and human resources, policies, and 
treatment guidelines), processes  refers to all those activities which 
constitute the delivery of health care (such as outpatient consulta-tions, or hospital admissions), while outcomes  refers to the conse-
quences of health care (such as changes in symptoms, disability, and quality of life). In relation to the evaluation of mental health services, we shall illustrate in this chapter how inputs and processes need to be measured and understood in their contribution to the outcomes of care.
Historically, the ﬁ  rst attempts to evaluate psychiatric practice orig-

inated in the mid-nineteenth century as the tabulation of admis-sions, discharges, and deaths in mental hospitals, simply describing the inputs and processes of care. In recent decades, as more sophisti-cated research methodologies and more valid and reliable research measures have been developed, so the evaluation of mental health services has increasingly focussed upon the analysis of the outcomes of care. As Sartorius has put it, ‘In its most classical form, evaluation denotes a comparison between results and goals of activity’ ,
(6) indi-
cating that evaluation has now become a purposeful exercise in which measurements are used as tools to answer speciﬁ  c questions, 
usually deﬁ  ned a priori at the beginning of a scientiﬁ  c study.
Why evaluate mental health services?
In our view, the main purposes of mental health service evaluation 
are to assess the effectiveness and cost-effectiveness of care, either

are to assess the effectiveness and cost-effectiveness of care, either 
at the organizational (local) or at the patient (individual) level. In the long-term such evidence can be used to provide better services for people with mental illness. For example, evaluation can be applied to comparing differing models of care, such as studies in England showing that home-treatment teams can provide a realis-tic alternative to emergency hospital admission.
(7–9) Evaluation 
therefore measures the impact of care (outcomes) and also aims to increase understanding of the active ingredients (inputs and pro-cesses) which contribute to better outcomes.
(1) In fact, a wider 
range of purposes can be served by the evaluation of mental health services, as shown in Table 7.6.2.
What to evaluate in mental health services?
In our view the most important focus of evaluation is upon the outcomes  of care.

(10, 11)  The outcome chosen for any particular

SECTION 7  social psychiatry and service provision 1464
evaluation will depend upon the central question addressed and 
the level at which outcomes are assessed, as shown in Table 7.6.3.
Directly in relation to the population level, a frequently used 
outcome measure is suicide rate (see cell 1C in Table 7.6.1). Rates of homelessness among mentally ill people (or rates of mental illness among the homeless) can also be used as an outcome indicator of the effectiveness of mental illness policies at the national (or regional) level.
At the local level, outcome indicators useful for evaluation can be 
made in three ways: (i) by interpolating from regional/national data; (ii) by measuring directly at the local level; and (iii) by aggregat-ing individual-level information up to the local level. For example, rates of suicide and unemployment can be estimated using the ﬁ  rst 
method, or directly measured using the second approach if the

method, or directly measured using the second approach if the 
appropriate data and resources exist, which will provide more 
accurate and up-to-date information. The third approach is to aggregate up to the local level information gathered from individual patients, if institutions providing care to those local patients are 
willing to cooperate in integrating their datasets.
At the individual level mental health service evaluation increasingly 
acknowledges the importance of outcomes other than symptom severity.
(10, 11) Traditionally, symptom severity measures  have 
been used most often to assess the effectiveness of the early, mental health treatments. Psychiatrists and psychologists have contributed to the early development of such assessment scales to allow this Table 7.6.1  Overview of the Matrix Model, with examples of inputs, processes, and outcomes
Place dimension Time dimension
(A) Input phase (B) Process phase (C) Outcome phase
(1) Country/regional level 1A 1B 1C

 Mental health budget allocation
 Mental health laws Government directives and policies
 Training plans for mental health staff
 Treatment protocols and guidelines  Performance/activity indicators (e.g. admission 
 rates, compulsory treatment rates) Overall suicide rates
 Homelessness rates Imprisonment rates
 Years lived with disability
(2) Local level 2A 2B 2C
 Local service budgets and balance for 
  hospital and community services Local population needs assessment
 Staff numbers and mix
 Clinical and non-clinical services Working relationships between teams Service contacts and patterns of service use
 Pathways to care and continuity Targeting of services to special groups Suicide rates among people with 
  mental illness Employment rates
 Physical morbidity rates
(3) Individual level 3A 3B 3C
 Assessments of individual needs made

mental illness Employment rates
 Assessments of individual needs made 
  by staff, service users, and by families Therapeutic expertise of staff
 Information for service users
 Information for family members Content of therapeutic interventions (both 
  psychological, social, and pharmacological)
 Continuity of clinical staff
 Frequency of appointments Symptom severity
 Impact on caregivers
 Satisfaction with services
 Quality of life Disability 
 Met and unmet needs
Table 7.6.2  Main purposes of mental health service evaluation
◆ To assess the outcomes of services in experimental conditions ( efﬁ  cacy )
◆  To investigate whether interventions which have demonstrated efﬁ  cacy  
under experimental conditions are also effective  in ordinary, routine clinical 
◆  To understand the mechanism of action (i.e. active ingredients) of 
◆  To inform mental health service investment decisions, for example using

◆  To inform mental health service investment decisions, for example using 
health economic data on cost-effectiveness
◆  To raise awareness among planners, policy makers, and politicians of 
service gaps
◆  To test a priori or to check post hoc  the value of planning decisions 
(for example, the closure of mental hospitals)Table 7.6 .3 Outcome measures suitable for use in routine clinical 
practice
Outcome measure Place dimension
Country level Local level Individual level
Employment status √√ √ √
Physical morbidity √√ √
Suicide and self-harm √√ √ √√
Homelessness √√ √
Standardized mortality ratios √√
Symptom severity √√ √
Impact on caregivers √√
Satisfaction with services √√ √
Quality of life √√
Disability √√ √
Met and unmet needs for care √√
Key: √ = suitable for use as an outcome, √√ = commonly used as an outcome.

1465
research to take place.(10,11) While the primary symptoms are clearly 
important, for most of the more severe mental disorders there is symptom persistence, and, at present, it is unrealistic to see symptom eradication as the sole aim of treatment. Therefore, very often, after the point of maximum symptom relief, when the extent of the ongoing impairments is clear, then the clinical task becomes one of attempting to minimize the consequent disability and handicap.
The importance of the impact of caring  for people with mental 
illnesses upon family members and others who provide informal care has long been recognized, but has only been subjected to con-certed research relatively recently.
(11–13) Such research has shown

(11–13) Such research has shown 
that it is common for carers themselves to suffer from mental ill-nesses, most commonly depression and anxiety, and to worry about the future when they may no longer be able to cope. Moreover, many family members are most distressed by the patient’s underac-tivity, and are often poorly informed about the clinical condition, its treatment, and the likely prognosis, as well as being inadequately provided with a practical action plan of what to do in the future should a crisis occur. Indeed, some services continue to convey to families the outmoded idea that carers, especially parents, are in some way to blame for the disorder or for relapses of the condition. The regular provision of information sessions for family members is now a hallmark of a good practice.
(14, 15)

(14, 15)
Patients’ satisfaction with services  is a further domain that has 
recently become established as a legitimate, important, and feasible area of outcome assessment.
(16) This is a recognition of the contri-
bution that service users and their carers can make to outcome assessment. Psychometrically adequate scales in this ﬁ  eld are those 
that adopt a multidimensional approach, assess the full range of service characteristics, are independently administered (so that patient ratings have no consequences upon their future clinical care), and have established validity and reliability.
(17)
Quality of life  ratings have also become prominent during the 
last decade, and several scales have been constructed that reﬂ  ect 
different basic approaches to the topic.(18) The ﬁ  rst distinction is

different basic approaches to the topic.(18) The ﬁ  rst distinction is 
between scales that address subjective well-being, compared with those that also measure objective elements of quality of life. The second main point of differentiation is between scales constructed for the general population and those designed for patients suffer-ing from speciﬁ  c disorders, including the more severe mental ill-
nesses.
(19) One advantage of quality of life data is that they tend to 
be popular with politicians, for whom the concept often has pow-erful face validity.
Among people with longer-term or more complex mental ill-
nesses, the measurement of disability  is often an important con-
sideration.
(20) Increasing importance is also being attached to the 
needs  of people with mental illness, where met needs are difﬁ  cul-
ties faced by people with mental illness in the presence of appropri-ate interventions.

(21) Needs (both met and unmet) may be deﬁ  ned 
by professionals/experts, or by service users, and in fact there is 
emerging evidence that service user ratings may be more informa-tive, for example in predicting quality of life.
(22–24)
Psychometric properties of outcome 
measures
Establishing the psychometric qualities of scales used for service 
evaluation is a central issue.(4) Among the most important charac-
teristics of outcome scales are validity and reliability. Validity refers to whether a scale actually measures what it is intended to measure. 
It is conventionally assessed in terms of face validity, content validity, consensual validity, criterion-related validity, and construct validity.
In addition, a rating scale must give repeatable results for the

In addition, a rating scale must give repeatable results for the 
same subject when used under different conditions, i.e. it must be reliable. There are four widely used methods to gauge reliability: inter-rater reliability, test–retest reliability, parallel-form reliability, and split-half reliability. The main issue for the evaluation of mental health services is to use wherever possible scales with known and adequate psychometric properties.
How to evaluate mental health services
In this section we consider research designs that may be applicable to the range of contexts used in mental health service evaluation.
(1)
Different types of evidence produced using these designs cannot be considered as equivalent. A hierarchical order has been proposed by Geddes and Harrison
(25) as shown in Table 7.6.4.
In terms of research methods or designs which can be used to

In terms of research methods or designs which can be used to 
produce such evidence, they can be considered as: (i) randomized controlled trial (RCT), (ii) quasi-experimental studies, (iii) case-control studies, (iv) cohort studies (prospective or retrospective), (v) cross sectional studies, and (vi) case series and single case studies. Since evaluations of mental health services are usually con-cerned with complex interventions, it is helpful to have an overall scheme linking different stages of research to test treatment inter-ventions. The Medical Research Council (MRC) framework for the evaluation of complex interventions sets out one such sequence, as shown in relation to anti-stigma interventions in Table 7.6.5. The elements in this scheme can be considered as sequential, or stages 0, 1, and 2 can be seen as one larger iterative activity.
(1) Nevertheless,

(1) Nevertheless, 
although this gives salience to randomized controlled trial designs, it is important to appreciate that research study designs need to be matched to the purpose of each type of evaluation, as shown in Table 7.6.6.
Evidence from a meta-analysis of randomized 
controlled trials
Meta-analysis can be deﬁ  ned as ‘the quantitative synthesis of the 
results of systematic overviews of previous studies’ , while systematic overviews, in turn, are methods of collating and synthesizing all the available evidence on a particular scientiﬁ  c question.
(26) Since ran-
domized controlled trials are often considered to produce the most sophisticated evidence on the efficacy of medical treatments, 
Table 7.6.4  Hierarchy of evidence
1a Evidence from a meta-analysis of RCTs
1b Evidence from at least one RCT
2a Evidence from at least one controlled study without randomization
2b Evidence from at least one other type of quasi-experimental study

3  Evidence from non-experimental descriptive studies, such as comparative 
studies, correlation studies, and case-control studies
4  Evidence from expert committee reports or opinions and/or clinical 
experience of respected authorities
(Reproduced from J.R. Geddes, and P .J. Harrison, Closing the gap between research and 
practice, The British Journal of Psychiatry , 171, 220–5, copyright 1997, The Royal College 
of Psychiatrists.)7.6 evaluation of mental health services

SECTION 7  social psychiatry and service provision 1466
a meta-analysis conducted on well selected and relevant random-
ized controlled trials can be seen as the highest order of knowledge. It follows that the quality of systematic overviews is limited by the quality and quantity of the contributory trials (see Table 7.6.7).
(27)
Cochrane was the ﬁ  rst to emphasize the need to bring together, 
within speciﬁ  c categories, the results of randomized controlled 
trials.(28) This approach is now central to evidence-based medicine. 
Within psychiatric evaluation the ﬁ  rst meta-analyses were conducted 
in the late 1970s, and more information is given on systematic reviews in Chapter 1.10 and 6.1 .
An illustration of such an exercise is the systematic overview and 
meta-analysis is that which reviewed RCTs comparing the out-comes of community mental health teams with those of standard care for patients with severe mental illness and disordered person-alities.

(29, 30)  They found 1200 citations using the search strategy: 70 
appeared relevant to the review, but only four studies satisﬁ  ed the 
inclusion criteria. The main results of this systematic review are that community mental health team management is associated with fewer deaths by suicide, with fewer people being dissatisﬁ  ed with 
services or leaving the studies early. No clear difference was found in admission rates, overall clinical outcomes, or in the duration of inpatient hospital treatment. The authors concluded that commu-nity mental health team management is not inferior to non-team standard care in any important respects, and is superior in promot-ing greater acceptance of treatment. It may also be superior in reducing hospital admissions and avoiding deaths by suicide.

The randomized controlled trials
The importance of randomized controlled trials within medical research has been expressed by Korn and Baumrind:
(31)‘Randomized clinical trials are the sine qua non for evaluating treatment in man’ . According to Barker and Rose: ‘the essence of the randomized controlled trial is that the outcome of the treat-ment given to one group of patients is compared with one or more other groups who are given different treatments or none at all. Allocation of individuals to the treatment and comparison groups is by random selection’ .
(32)
The advantages of the research design of these studies have been 
extensively described(33) and are shown in Table 7.6.8 (see also 
Chapter 1.10 in this book). However, the design limitations of such trials also need to be appreciated, particularly in relation to health service research, as shown in Table 7.6.9.
(34)
In addition to the technical limitations of the trial design, there

(34)
In addition to the technical limitations of the trial design, there 
are also situations where randomized controlled trials are not applicable to speciﬁ  c research questions. These can be summarized 
as conditions in which randomized controlled trials are inadequate, impossible, inappropriate, or unnecessary, as shown in Table 7.6.10. Nevertheless, where they are appropriate, it will be necessary to use explicit criteria to assess the quality of such trials, such as those shown in Table 7.6.11.
(35, 36)
It is now common to distinguish between efﬁ  cacy trials  (which 
tend to be explanatory) and effectiveness trials  (sometimes other-
wise called large simple, pragmatic, practical, or management trials).
(33, 37–39)  This categorical distinction has its uses, although 
Table 7.6 .6 Research aims and appropriate study designs
Research aim Appropriate study designs
Service description Cross sectional survey
Assess intervention Quasi-experimental study (e.g.

Assess intervention Quasi-experimental study (e.g. 
controlled before–after comparison)
Randomized controlled trial
Identify prognosis for a condition Cohort study
Establish aetiology of a condition Cohort study
Case-control studyTable 7.6.5  Phases of the Medical Research Council framework for the evaluation of complex interventions(1, 2)
0 Preclinical 1 Modelling/manualization 2 Exploratory 3 Deﬁ  nitive trial 4 Long-term implementation
Explore relevant theory 
to ensure best choice of 
intervention and hypothesis 
and to predict major confounders and strategic 
design issuesIdentify the components of the 
intervention and the underlying mechanisms by which they will 
inﬂ  uence outcomes to provide 
evidence that you can predict 
how they relate to and interact with each otherDescribe the constant and

how they relate to and interact with each otherDescribe the constant and 
variable components of a replicable intervention and a feasible protocol for comparing the intervention 
with an appropriate 
alternativeCompare a fully deﬁ  ned 
intervention with an appropriate 
alternative using a protocol 
that is theoretically defensible, reproducible, and adequately 
controlled in a study with 
appropriate statistical powerDetermine whether others 
can reliably replicate your 
intervention and the results in 
uncontrolled settings over the long-term
Example: anti-stigma 
intervention in schools study
Social contact theory
(69) Yes Completed(70) Planned Potential if preceding phases 
successful
Table 7 .6.7 Characteristics of systematic overviews
Questions to ask about papers for potential inclusion in a systematic 
overview

overview
◆ Were the questions and methods clearly stated?
◆ Were comprehensive search methods used to locate the relevant articles?
◆  Were explicit methods used to determine which articles were included in 
the review?
◆ Was the methodological quality of the primary studies assessed?
◆  Were the selection and assessment of the primary studies reproducible and 
free from bias?
◆ Were the differences in individual study results adequately explained?
◆ Were the results of the primary studies combined appropriately?
◆ Were the reviewer’s conclusions supported by the data cited?
(Reproduced from S.I. Sackett and J.E. Wennberg, Choosing the best research design for 
each question, British Medical Journal , 315 (7123), 1636, copyright 1997, BMJ Publishing 
Group Ltd.)

1467
for some purposes we may rather see efﬁ  cacy and effectiveness tri-
als as falling along a continuum. Efﬁ  cacy trials, which usually pre-
cede effectiveness studies, refer to those conducted under more ideal, experimental conditions, while effectiveness trials are RCTs carried out in more routine clinical conditions.
(28, 40–42)
Nevertheless, some important questions, for example the impact of clinical guidelines, may only be researchable in real world settings, and will therefore bypass the efﬁ  cacy study stage.
(43)
Cochrane has deﬁ  ned effectiveness, at the patient level, as assess-
ing whether an intervention does more good than harm when provided under usual circumstances of health care practice.
(28) At 
the level of service provision, Wells has deﬁ  ned effectiveness trials 
as those which ‘duplicate as closely as possible the conditions in the target practice venues to which study results will be applied’ .
(44)

(44)
The key differences between efﬁ  cacy and effectiveness trials are 
shown in Table 7.6.12, although in practice the differences between these types of trial may not necessarily be as great as the differences between pharmacological, psychological, and service interventions (such as the dissemination, and related barriers, of proven inter-
ventions).
(45–47)
In planning effectiveness RCTs, seven sets of issues need to be 
carefully considered: (i) study question (e.g. is the study question expressed in an answerable way?), (ii) reference population (e.g. what is the reference group or subgroup to which the trial results should be generalized?), (iii) patient sample (e.g. how far does the sample reﬂ  ect the target population?), (iv) study settings (e.g. how

representative are the study settings of routine clinical sites?), (v) study interventions (e.g. is the study intervention manualized, acceptable to patients, and suitable for widespread use?), (vi) control condition (e.g. are the key characteristics of the control condition well described, and do they vary within and between sites?), and (vii) bias (e.g. attrition, blinding, concealment, consent, and Table 7.6 .8 Advantages of RCTs
◆ Controls for many confounding variables which may exist
◆ Eliminates the effects of spontaneous remission
◆ Eliminates regression to mean
◆ Eliminates placebo effect
◆ Independent of rater bias if blindness maintained
◆ Basis for systematic reviews
Table 7.6 .9 Limitations and disadvantages of RCTs designs
1. Difﬁ  culties in choosing the unit or level of random allocation
◆  Should allocation be made at the patient level, the clinician level, the clinical 
team/practice level, or the locality level?
2. Difﬁ  culties in achieving random allocation

◆  Randomization not possible
◆  Particular patient groups excluded
◆  Self-exclusion because of non-consent
3. Difﬁ  culties in obtaining consent and in maintaining motivation
◆  Consent may be inversely proportional to severity of condition
◆  Consent may be refused because of patient treatment preferences
◆  Retention with the trial may be affected by patient motivation
4. Difﬁ  culties in establishing and maintaining blindness
◆  Degree of blinding of subjects
◆  Degree of blinding of staff
◆  Degree of blinding of raters
◆  Deactive Hawthorne effect (the effect of being studied upon those being 
studied)
5. Difﬁ  culties related to the experimental conditions
◆  Concurrent multiple interventions in health service research trials (without 
a single potentially active ingredient)

studied)
◆  Interactions between treatment components
◆  Consistency of control (‘usual treatment’) conditions
◆  High attrition rates or loss to follow-up
   Large differences between conditions in which trials can take place and 
those of routine practiceTable 7.6.10  Situations when RCT designs are not applicable
1. Situations in which experimentation is inadequate
◆ Poor generalizability—low external validity
◆ Unrepresentative staff included
◆ Atypical patients included
◆ Treatments not standardized
2. Situations in which experimentation is impossible
◆ Refusal of clinicians to take part
◆ Ethical objections to the study
◆ Political barriers
◆ Legal objections
◆ Contamination between experimental and control conditions
◆ Scale of task—trials are required for too many treatments

3. Situations in which experimentation is inappropriate
◆ Studies conducted to reduce the occurrence of events of very low frequency
◆ Studies to prevent unwanted outcomes in the distant future
4. Experimentation unnecessary
◆ When beneﬁ  t/risk ratio is dramatic
◆ When there is a small likelihood of confounders
(Reproduced from N. Black (1996), Why we need observational studies to evaluate the 
effectiveness of health care, British Medical Journal , 312 (7040), 1215–18, copyright 1997, 
BMJ Publishing Group Ltd.)
Table 7.6.11  Criteria to evaluate the quality of an RCT
Criteria
 1. Is the hypothesis clearly deﬁ  ned?
 2. Is the study population representative? 3. Was patient assignment randomized? 4.  Were patients, practitioners, and assessors blind to the experimental 
intervention?

2. Is the study population representative? 3. Was patient assignment randomized? 4.  Were patients, practitioners, and assessors blind to the experimental 
 5. Were the groups similar at the start of the trial? 6. Were the groups treated equally apart from the experimental intervention? 7. Were all those who entered the trial accounted for at its conclusion?
 8. Was this in the groups to which they were originally allocated?
 9. Are all clinically important outcomes considered?10. Whose perspective do they reﬂ  ect?11. Is the data analysis appropriate?12. What is the size and precision of the treatment effect?13. Do the likely beneﬁ  ts outweigh the harms and risks?14. Is the conclusion supported by the results?7.6 evaluation of mental health services

SECTION 7  social psychiatry and service provision 1468
contamination). These issues are shown in more detail in 
Tables 7.6.13 and 7.6.14.(48)
Quasi-experimental studies
The term ‘quasi-experiment’ was ﬁ  rst used to refer to a situation in 
which the decision about whether an individual does or does not receive the intervention to be evaluated is not under the investiga-tor’s control.
(49) Random allocation of patients is therefore 
not made, so selection bias may occur. In other respects, a quasi-experiment aims to apply the logic of randomized controlled trials to the study design, and the researcher tries to reduce this bias by making the study units, in the groups being compared, as alike as possible in terms of the most important characteristics. This approach is known as matching . Characteristics chosen for match-
ing are those expected to inﬂ  uence the outcome (i.e. confounding

ing are those expected to inﬂ  uence the outcome (i.e. confounding 
factor). Therefore, the overriding aim of matching is to reduce the contribution made by the matched variables to the selection bias, although this method is inferior to randomization in that it cannot reduce the selection bias from all other variables.There are two main approaches to matching. Paired matching
consists of selecting individuals for the comparison group (or gr oups)
who have closely similar characteristics to those included in the experimental group, for example in terms of age, gender, and occupation. This form of prestratiﬁ  cation will need to be taken 
into account at the data analysis stage. A less rigorous variant is group matching , which only ensures that there are similar overall 
proportions of people, for both the experimental and comparison groups, in the various age bands, occupational groups, or other predeﬁ  ned strata used for the variables chosen for matching.

Non-experimental descriptive studies
The next type of research design included in the hierarchy of evidence 
is non-experimental descriptive studies. For the sake of clarity and brevity we shall distinguish two types of descriptive study: struc-tured clinical practice and everyday unstructured clinical practice. An example of a descriptive evaluation design is the South Verona Outcome Study.
(50, 51) This is a prospective study, which aims to Table 7.6.12  Key differences between efﬁ  cacy and effectiveness trials
Efﬁ cacy trials Effectiveness trials
Goal To estimate efﬁ  cacy and safety (if relevant) usually of a 
speciﬁ  c clinical interventionTo estimate relative beneﬁ  ts and risks of approved treatments, clinical 
interventions, programmes, or policies

When Usually before an intervention is introduced Post-implementationDiagnosis Diagnosis by structured interview Clinical diagnosis or structured interview
Inclusion and exclusion 
criteriaStrict and multiple inclusion and exclusion criteria, typically 
excluding patients with comorbid physical and psychiatric 
disordersRelatively few inclusion and exclusion criteria to optimize external 
validity of sample
Patient sample Typically enrol highly motivated patients Attempt to include more representative patients, including those 
who are ambivalent and who may not adhere to the allocated 
treatment regime
Sample size At most a few hundred, more often less than 100 Often larger to enable smaller effect sizes to be identiﬁ  ed in 
heterogeneous populations (e.g. in large simple trials with dichotomous outcomes)

Comparator Placebo and/or single active comparator (for drug trials) One or more active comparators (for drug trials)
Treatment as usual or active control (for psycho-social 
interventions)Treatment as usual or active control (for psycho-social interventions)
Dosing Fixed or ﬂ  exible Flexible dosing in clinically used range
Blinding Triple-blind (i.e. patients, staff, and researchers blind), or 
double-blindDouble-blind (where possible), or single-blind
Duration 1–4 months 6 months or more
Research sites Small number of experienced research sites Dozens of routine treatment sites
Delivery of intervention According to manual or protocol, not a fo cus of research Fidelity to manual a key variable, and study ma y consider barriers to 
delivery of intervention in routine practice
(47)
Research protocol Strictly deﬁ  ned Deliberately similar to usual practice

(47)
Adjunctive treatments Not allowed or strictly limited Allowed as in usual practice
Outcomes Symptom rating scales and other clinical parameters A single well-deﬁ  ned, clinically important outcome (for large simpl e 
trials) and multiple secondary outcomes, including safety and costs 
(for practical trials)
(Reproduced from S. Stroup, Practical clinical trials for schizophrenia, Epidemiologia e Psichiatria Sociale , 14, 132–6, copyright 2005 II Pensiero Scientiﬁ  co Editore.)

1469
assess the outcome of mental health care. Data from this study have 
been analysed using a multidimensional perspective. Among 354 patients followed up after 6 years of treatment in routine clini-cal settings the study revealed a complex pattern of emerging and disappearing clinical and patterns of exacerbation and remissions, with both changing frequently over time, but changes in both clinicial and social domains were not associated with diagnosis.
(52)
Over the course of the next decade we expect that the following key trends will be of paramount importance. In relation to the focus of research, in many countries a degree of contestability may well devel-
op, in which those who have traditionally identiﬁ  ed questions to be 
addressed by research (investigators) will be challenged by research funders (such as governments and charities) and by the intended beneﬁ  ciaries of the research (people with mental illness and their

family members) to set the research agenda.
(53) We can expect gov-
ernments to direct their research investment towards policy chal-lenges, such as barriers to the implementation of evidence-based practice.
(54–56)  This may well include the commissioning of research 
not just on new treatments and services, but also to evaluate already or even long-established models of care. For example, there is rela-tively little mental health service evaluation about: outpatient ser-vices (clinics), inpatient services, or forensic service provision.
(57, 58)
In future, it will be important to evaluate post hoc  current but unprov-
en service conﬁ  gurations, particularly those that are widespread and 
expensive, as well as innovative interventions. This will necessitate providing sufﬁ  cient long-term funding for health service research.
In terms of study design, we anticipate that there will be a relative

In terms of study design, we anticipate that there will be a relative 
growth of effectiveness studies, especially RCTs, which attempt to balance internal and external validity.
(48) These will more often 
than in the past specify the precise nature of the control condition, use representative patient samples, and standardized outcomes measures. Less common study designs, such as cluster and preference RCTs will be necessary to tackle complex interventions.
(59, 60)
The recent trend to more often include qualitative assessments Table 7.6.13  Criteria to plan effectiveness randomized 
controlled trials(48)
1. Study question
◆ Who deﬁ  nes the aim of the study?
◆ What process is used to identify the question addressed?
◆  Is the study question expressed in an answerable way? (as a clear 
hypothesis)
◆ Prior evidence of intervention effect size
◆ Is the answer to this question really unknown?
◆ Why is this question important now?

◆  Is there initial evidence from efﬁ  cacy trials or effectiveness studies? 
(observational or trials)
◆  What is the public health importance of the policy or practice question 
addressed?
◆ What is the clinical necessity of the question?
◆  Sample size and statistical power for primary/secondary aims and related 
hypotheses
2. Reference population
◆  What is the reference group (or subgroup) to which the trial results should 
be generalized?
◆ What are their socio-demographic and clinical characteristics?
◆ What are the ethnic and cultural characteristics of the target group?
◆ What is resource level in this population?
◆ What is the nature and standard and coverage of health and social care?
◆ At what time point is population identiﬁ  ed?
3. Patient sample
◆ What are their socio-demographic, and clinical characteristics?

◆ What are the inclusion criteria?
◆ Not invited to participate rate
◆ Non-participation rate
◆ Patient preferences
◆ What are the exclusion criteria?
◆ How far does the sample reﬂ  ect the target population?
◆ What level of heterogeneity is there?
◆  Selection of incident or prevalent cases (true incidence/prevalence or 
treated incidence/prevalence)
◆  What are the rates of adherence and non-adherence to treatment as 
recommended?
4. Study settings
◆ Characteristics and representativeness of professional staff
◆ Levels of resources available
◆ Research oriented culture
◆ Staff morale and sustainability of intervention
◆ Incentives for research collaboration
◆ Opportunities for data linkage
◆ Centre/professional non-participation
5. Study intervention
◆ Is intervention acceptable?
◆ Total time needed to deliver intervention
◆ Frequency of interventions

◆ Simplicity/complexity of the intervention
◆ Single/multi-component intervention
◆ Is intervention manualized?
◆ Do usual professional staff deliver the intervention during the study?
◆ Can treatment process be measured? (ﬁ  delity)
◆ Degree of ﬁ  t/feasibility for current practice
◆ Exit strategy, who pays after the end of study6. Control condition
◆ Treatment as usual or speciﬁ  c control
◆ Acceptability to patients of control condition
◆ Cost and feasibility of control condition
◆ Variation between control condition within and between sites (ﬁ  delity)
◆ Are the key characteristics of the control condition well described?
7. Bias
◆ Does contamination take place?
◆ Degree of blinding
◆ Choice of primary and secondary outcomes
◆ Perspectives prioritized in outcome choice

7. Bias
◆ Time(s) at which outcomes measured
◆ Total length of follow-up and late effects
◆ Sources of outcome data
◆ Respondent burden
◆ Consent rate
◆ Recruitment rate
◆ Attrition/drop-out and follow-up rates
(Reproduced from Tansella, M. Thornicroft, G., Barbui, C. et al.  Seven criteria for improv-
ing effectiveness trials in psychiatry. Psychological Medicine , 36(5) 711–200, copyright 
2006, Cambridge University Press.)7.6 evaluation of mental health services

SECTION 7  social psychiatry and service provision 1470
within RCTs we expect to accelerate, for example to identity the 
acceptability of interventions to patients, and to identify the active ingredients (and barriers) to treatment effectiveness.
(61–65)
How will the conduct of evaluations of mental health services 
evolve in the coming years? We can identify a trend for study inter-ventions to be increasingly often manualized. At the same time the patient populations treated will be more often similar to those treated in routine clinical practice. As a consequence, more attention will need to be paid to ways to incentivize clinical staff to participate in research.
Although traditionally research scientists have seen the dissemi-
nation of research ﬁ  ndings largely in terms of publications in 
scientiﬁ  c journals,
(66) it is likely that research funders will increas-

ingly encourage or even insist upon using effective and target-speciﬁ  c communication methods to reach key audiences with the 
results of research and their implications, including non-traditional methods such as social marketing.
(67) This will be intended to alter 
the behaviour of service planners, commissioners, practitioners, and service users, so that the results of research do inﬂ  uence the 
behaviour of these key groups in terms of service decisions, so that they increasingly reﬂ  ect the evidence both of effective interventions

behaviour of these key groups in terms of service decisions, so that they increasingly reﬂ  ect the evidence both of effective interventions 
and where the evidence shows lack of effect then to stop ineffective practices and services. Such behaviour change (and an established evidence base for this) may include methods as social marketing, as well as carefully combined interventions such as those used in case management in the treatment of depression.
(68)Further information
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Tansella, M. and Thornicroft, G. (2001). Mental health outcome measures
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Fulop, N. and Allen, P . (2002). Studying the organization and the delivery of 
the health services: research methods . Routledge, London.
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mental health service: a pragmatic balance of community and hospital care. The British Journal of Psychiatry ,185, 283–90.
Thornicroft, G., Becker, T., Knapp, M., et al.  (2006). International outcome 
measures in mental health. Quality of life, needs, service satisfaction, costs and impact on carers. Gaskell, Royal College of Psychiatrists, London.
Slade, M. and Priebe, S. (2006). Choosing methods in mental health research .
Knapp, M.J., McDaid, D., Mossialos, E., et al.  (2007). Mental health policy 
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Focus of research
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◆ Including service users and family members in setting research questions
◆ Asking clear research questions to answer important clinical challenges
◆ Evaluating already established as well new services
◆ Providing sufﬁ  cient funding for long-term health service research
Study design
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◆ Moving from efﬁ  cacy to effectiveness trials
◆ Specifying the precise nature of the control condition
◆ Using representative patient samples
◆ Using standardized outcome measures

◆ Combining qualitative and quantitative information
Conduct of research studies
◆ Manualizing the interventions to be evaluated
◆ Specifying the key characteristics of the patient groups to be treated
◆ Incentivizing clinical staff to participate in research
Data analysis and interpretation of ﬁ  ndings
◆ Identifying the active ingredients of effective interventions
Dissemination of research ﬁ  ndings
◆  Using effective and target-speciﬁ  c communication methods to reach key 
audiences with the results of research and their implications
Implementation of effective interventions
◆  Implementing the results of evaluation when the evidence is strong enough 
and decommissioning ineffective practice

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72. Stroup, S. (2005). Practical clinical trials for schizophrenia. 
Epidemiologia e Psichiatria Sociale ,14, 132–6.

7.7
Economic analysis of 
mental health services
Economics is concerned with the use and distribution of resources 
within a society, and how different ways of allocating resources impact on the well-being of individuals. Economics enters the health sphere because resources available to meet societal needs or demands are ﬁ  nite, meaning that choices have to be made regarding 
how best to allocate them (typically to generate the greatest possible level of population health). Economics provides an explicit frame-work for thinking through ways of allocating resources.
Resource allocation decisions in mental health are complicated

Resource allocation decisions in mental health are complicated 
by the fact that disorders are common, debilitating, and often long-lasting. Epidemiological research has demonstrated the considerable burden that mental disorders impose because of their prevalence, chronicity, and severity: globally, more than 10 per cent of lost years of healthy life and over 30 per cent of all years lived with disability are attributable to mental disorders.
(1) Low rates 
of recognition and effective treatment compound the problem, particularly in poor countries.
However, disease burden is not in itself sufﬁ  cient as a justiﬁ  cation

However, disease burden is not in itself sufﬁ  cient as a justiﬁ  cation 
or mechanism for resource allocation or priority-setting. A disorder can place considerable burden on a population but if appropriate strategies to reduce this burden are absent or extremely expensive in relation to the health gains achieved, large-scale investment would be considered misplaced. The reason is that scarce resources could be more efﬁ  ciently channelled to other burdensome conditions for 
which cost-effective responses were available. For priority-setting and 
resource allocation, it is necessary to ask what amount of burden from a disorder can be avoided by using evidence-based interventions, and at what relative cost of implementation in the target population.
Cost and cost-effectiveness considerations enter into health care

Cost and cost-effectiveness considerations enter into health care 
reform processes, priority-setting exercises within and across health programmes, and regulatory decisions concerning drug approval or pricing. Two broad levels of economic analysis can be distin-guished: macro and micro.
Economic analyses at macro level: the 
mental health system
Macro-level economic analyses are concerned with how health 
systems function and what they achieve. What, for example, are the motivations and behaviour of key ‘stakeholders’ , with what implications for access, quality, and costs? What roles do economic 
forces play and can they be shaped to improve health outcomes and cost-effectiveness? Do different organizational or ﬁ  nancial arrange-
ments produce different resource conﬁ  gurations? For example, do 
markets achieve fairer or more efﬁ  cient allocations than state

markets achieve fairer or more efﬁ  cient allocations than state 
bureaucracies? Through their macro analyses, economists can con-tribute to a better understanding of how health systems can improve utilization of resources (for example, see Box 7.7.1).
While improved psychological well-being in the population is 
likely to represent the primary goal of the mental health system, there are other (social) goals that could also feature prominently, including quality improvements in service provision, and ﬁ  nancial 
(as well as human rights) protection for people with mental health 
problems.
(2) Meeting these goals is achieved via a number of key 
health system functions, including resource generation, their allo-cation via appropriate modes of ﬁ  nancing, actual provision of 
services, and overall stewardship and evaluation of these various functions.
(3) Economic analysis contributes to policy formation

(3) Economic analysis contributes to policy formation 
relating to each of these functions.(4–6)
There are barriers to implementation of evidence-based mental 
health care in even generously resourced health systems. An insidiousbarrier is resource insufﬁ  ciency: mental health services are often 
grossly under-funded in comparison to both needs and the 
Box 7.7.1 The relevance of a health systems perspective
The need for a systems approach to mental health policy and

The need for a systems approach to mental health policy and 
planning is made apparent from a simple illustration: cheap, effective drugs exist for key neuropsychiatric disorders, including tricyclic antidepressants, conventional neuroleptics, and anti-epileptic drugs, which are affordable even to resource-poor countries. The availability and prescription of these drugs to those in need, however, are determined by the extent to which such drugs have been distributed and by the ability of health care providers to detect and appropriately treat the underlying condition. Access to and use of such medications may further be hampered by the private cost of seeking and receiving health care, particularly if it is out-of pocket. User fees, provider incen-tives, and clinical practice are in turn inﬂ  uenced by the availability

SECTION 7  social psychiatry and service provision 1474
cost-effectiveness of interventions to meet them. This is a major 
issue for countries where the proportion of national income devoted to health care is low, or where the proportion of the health budget allocated to mental health is minimal. With limited funds it is difﬁ  cult to build any kind of service system, because it is difﬁ  cult 
to recruit, train, and retain skilled staff.
Even when resources are committed, available services might be

Even when resources are committed, available services might be 
poorly distributed, available at the wrong place or time relative to the distribution of needs. They may only be delivered by specialist clinics or concentrated in big cities, or affordable only by wealthier individuals. Improvements to practice take time to work through to improved health outcomes, cost-effectiveness gains or fairer access, even when suitable professionals can be recruited or new facilities opened. Decision makers must think long-term, for the immediate consequences of many interventions could be modest but longer-term beneﬁ  ts immense.
(7)
A more general difﬁ  culty is that available services do not match

(7)
A more general difﬁ  culty is that available services do not match 
what is needed or preferred. Indeed, there may be scant informa-tion on population or individual needs, and patients may have few opportunities to participate in treatment decisions. Another prob-lem could be poor coordination of services because of professional rivalry, stultifying bureaucracy or ‘silo budgeting’ (resources held in one agency’s ‘silo’ cannot be allocated to other uses).
Economic analyses at micro level: 
cost-effectiveness
The most frequently posed micro questions relate to the cost-effec-
tiveness of interventions, such as an emphasis on community-based care, the use of new drugs, or the development of secure accom-modation. For example, consider what happens following develop-ment of a new treatment (say a new medication for schizophrenia). Decision makers want answers to two questions when considering whether to use or recommend this drug. The ﬁ  rst is the clinical

question: is it effective in alleviating psychotic symptoms and generally improving health-related quality of life? If the answer to the clinical question is ‘yes’ , then there is a second question: is it cost-effective? That is, does the drug achieve the improved outcomes at a cost that is worth paying? The meaning of ‘worth’ is far from straightforward to establish and laden with controversy.
These two questions sit at the heart of economic evaluation: 
outcomes must be assessed (and compared between different 
treatments) and the (relative) costs of achieving them must be examined. Looking only at costs is not an economic evaluation.
There are different variants of economic evaluation. They share a 
common approach to the conceptualization, deﬁ  nition, and meas-

urement of costs, but adopt different approaches when considering and measuring outcomes, primarily because they seek to answer slightly different questions. We set out these differences by discuss-ing the questions a study might address, measuring costs and out-comes, making trade-offs between them, and utility and beneﬁ  t 
measurement.
Question and perspective
The choice of evaluative approach depends on the question to be addressed. If the question is essentially clinical—what is the most appropriate treatment for someo ne with particular n eeds in particu-
lar circumstances—information is needed on the comparative costs of alternative treatments and comparative outcomes meas ured in terms of symptom alleviation, improved functioning, and so on. 
A cost-effectiveness analysis would be appropriate (see ‘Effectiveness measurement’ below).

If, to take a broader stance, the question is whether to treat 
depression rather than spending the funds elsewhere in the health system, then decision makers need to know the costs, but now need an outcome measure that uses a common metric across different health domains. The most common such metric is ‘utility’ and a c ost-
utility analysis would be undertaken (see ‘Utility measurement’ below).
T o widen the perspective further, if the question is whether to 
increase expenditure in the health system or in (say) improving transport or launching a new environmental policy, then an evalu-ation needs to ask about the comparative costs and impacts of the different options, where ‘impact’ will need to be measured in a common unit across all public policy areas. The usual choice of broad measure is monetary, leading to cost–beneﬁ  t analysis (see ‘Beneﬁ  t 
measurement’ below).

The question to be addressed thus inﬂ  uences the type of evalua-
tion needed, but the choices are not mutually exclusive: a single study can support more than one approach if the right measures are used. The broader the question, the lower the likelihood that the outcome measure will be sensitive to the particular circum-stances of a speciﬁ  c disorder such as depression, but the greater the 
usefulness in terms of resource allocation decisions.
Linked to speciﬁ  cation of the question to be addressed is the 
perspective  of a study. Is the evaluation needed to help resource 
allocation within a particular agency (such as primary care clinic), or a particular system (such as the health care system), or the whole society? The perspective will determine the breadth of both cost and outcome measurement.
Cost measurement

Some costs are directly associated with a disorder or its treatment, such as the money spent on medications and services used by patients, and some are more indirect, measuring lost productivity because ill-health can disrupt someone’s employment pattern or 
the social cost of unpaid care provided by families. How broadly the costs are measured will depend upon the purpose of the study.
In carrying out evaluations in practice, economists need data on 
service use patterns by patients. This information might come from organizational ‘billing’ systems (recording amounts transferred between purchasers and providers for  services used), or from routine 
information systems that record service contacts, or from research instruments that speciﬁ  cally collect data on service use patterns 
through interviews with patients, caregivers, or service profession als. 
One widely used instrument is the Client Service Receipt 
Inventory.
(8)

(8)
The next task is to attach unit cost estimates to these service use 
data. In England, there is an excellent annual compendium of health and social care unit costs, which provides just such ﬁ  gures.
(9)
In other countries, it might be necessary to estimate unit costs 
anew. A range of data sources could be used, including government statistics, health system expenditure ﬁ  gures, and speciﬁ  c facility or 
organization accounts. The main cost categories to be quantiﬁ  ed 
would be:
◆ salaries of staff employed in patient treatment and care
◆ facility operating costs (e.g. cleaning, catering)

1475
◆ overhead costs (e.g. personnel, ﬁ  nance)
◆ capital costs for buildings and durable equipment
Effectiveness measurement
The most intuitive mode of economic evaluation is cost-effective-
ness analysis (CEA): it measures costs as set out above, and out-comes along the dimensions that would be recognized by clinicians and used in clinical studies (changes in symptoms, behaviour, functioning, and so on). A CEA can help decision makers choose between interventions aimed at speciﬁ  c health needs. A cost-
effectiveness analysis looks at a single outcome dimension—such as change in symptoms—and computes and compares the differ-ence in costs between two treatments and the difference in this (primary) outcome. If one treatment is both more effective and less costly than another, then it would clearly be the more cost-effective of the two. But if it is more effective and more  costly then a trade-
off is needed (see below).
Often the economist will compute cost differences and a range

Often the economist will compute cost differences and a range 
of effectiveness differences (one for each outcome dimension)—an 
approach sometimes called cost-consequences analysis—which has the advantage of breadth but poses a challenge if one outcome is better and another worse for a particular treatment. It is then not always obvious which treatment is to be preferred, and the decision maker must weigh up the strength of evidence.
Making trade-offs
If an evaluation ﬁ  nds a new intervention to be both more effective 
but simultaneously more expensive than an older intervention, which is the more cost-effective of the two? A trade-off must be made between the better outcomes and the higher costs necessary to achieve them.
The classical way of determining this trade-off has been via the 
derivation of a incremental cost-effectiveness ratio (CER), which divides the extra cost associated with a new intervention by its additional effect (see Box 7.7.2).

More recently, health economists have developed the ‘net beneﬁ  t 
approach’ to explicate the nature of the trade-off (see Box 7.7.3 for an example). It is commonly seen today in the construction of cost-effectiveness acceptability curves  (CEACs). These curves show 
the probability that an intervention will be cost-effective for each 
of a number of pre-speciﬁ  ed or implicit valuations of an outcome 
improvement by the decision maker.
Utility measurement
One way to overcome the potential problem of different outcome dimensions pointing in different directions is to employ a single, over-arching measure. A preference-weighted, health-related quality

One way to overcome the potential problem of different outcome dimensions pointing in different directions is to employ a single, over-arching measure. A preference-weighted, health-related quality 
of life measure could be used. The value of the quality of life improvement is gauged in units of ‘utility’ , usually expressed by a combined index of the mortality and quality of life effects of an intervention. The best known such index is the Quality Adjusted 
Life Y ear (QALY).
A cost-utility analysis (CUA) measures the outcome difference 
between two interventions in terms of QALY gain, and compares this with the difference in costs. CUAs have a number of attractions, including a unidimensional, generic outcome measure that allows comparisons across diagnostic groups, based on an explicit methodology for weighting preferences and valuing health states. But the utility measure may be too reductionist and insufﬁ  ciently

sensitive to changes expected in a particular clinical area such as depression treatment.
(11) Nevertheless, cost-utility analyses produce 
estimates of cost-per-QALY gain from one therapy over another, which can then inform health care resource allocation decisions, such as by the National Institute for Health and Clinical Excellence (NICE) in England and Wales.
Beneﬁ  t measurement
Cost–beneﬁ  t analysis asks whether the beneﬁ  ts of a treatment or 
policy exceed the costs, helping decision makers to allocate resources across a wide area, for example comparing health care with housing, education, or defence. All costs and outcomes (beneﬁ  ts) 
are valued in the same (monetary) units. If beneﬁ  ts exceed costs, 
the evaluation would provide support for the intervention or programme, and vice versa. With two or more alternatives, the intervention with the greatest net beneﬁ  t would be deemed the 
most efﬁ  cient. Cost–beneﬁ  t analyses are thus intrinsically attrac-

tive, but conducting them is especially problematic because of the difﬁ  culties associated with attaching monetary values to health 
outcomes, and especially mental health outcomes. Methodological advances in health economics offer ways to obtain direct valuations of health outcomes by patients, families, or others,
(12) but they will 
not be easy to apply in mental health contexts.
Design issues
As in clinical evaluation, an important consideration for the review, assessment, and interpretation of economic evidence is research Box 7.7.3 Example of the net beneﬁ  t approach in mental 
health services research
An example of the use of cost-effectiveness acceptability 
curves comes from a study of computer-delivered cognitive behavioural therapy (CCBT) for anxiety and depression.
(10)

(10)
CCBT was more expensive in health service terms than standard primary care services, but more effective in reducing symptoms. The ﬁ  tted CEACs showed that, even if the value placed by society 
on a unit reduction in the Beck Depression Inventory (the primary clinical measure used in the trial) was as little as £40, there was an 81 per cent probability that CCBT would be viewed as cost-effective. Similarly, assigning a societal value of just £5 to each additional depression-free day would result in an 80 per cent probability that CCBT would be cost-effective. The CEAC makes transparent the trade-offs faced by decision makers.
Box 7.7.2 Calculation of the incremental cost-effectiveness 
ratio
For example, evaluation of a new antidepressant may show that

ratio
For example, evaluation of a new antidepressant may show that 
the cost per treated case of major depression is an extra £500 per year but also results in a lower average symptom score over this period (such as a ten point reduction on the Beck Depression Inventory); the resulting incremental CER would therefore be £50 [£500/10], meaning that each additional unit improvement on the BDI cost £50.7.7 economic analysis of mental health services

SECTION 7  social psychiatry and service provision 1476
design. Generally speaking, the ideal type of study upon which to 
base decisions on cost-effectiveness and resource allocation is the one conducted prospectively with two (or more) appropriately sized randomly allocated groups of patients, for whom all conceiv-able costs and outcomes are measured appropriately, including a comparable measure of outcome (monetized beneﬁ  ts or, more 
realistically, a utility metric).
Looking across the mental health ﬁ  eld, the accumulation of new

Looking across the mental health ﬁ  eld, the accumulation of new 
cost-effectiveness evidence has been uneven, tending to be greater in diagnostic areas where new classes of medication have been launched: the pharmaceutical industry looks to economic evidence to support its marketing. At the same time, health care funding and delivery bodies also want their own independent evidence on new therapies. Consequently, a lot of economic studies of depression followed the licensing of the early selective serotonin-reuptake inhibitors (SSRIs) and later antidepressants with other mechanisms of action. Similarly, the arrival of the atypical antipsychotics and the cholinesterase inhibitors for Alzheimer’s disease stimulated a lot of economics research.
We cannot cover all mental health areas here. Instead, in the 
next three sections, we look at areas where there has been some interesting activity:
◆ cost-utility analysis of depression treatment in primary care

◆ cost-effectiveness of interventions for child and adolescent 
◆ sectoral cost-effectiveness analysis of mental health interventions 
in developing countries.
Cost-utility analysis of depression treatment 
in primary care
T en years ago, examples of the application of the cost-utility 
approach to mental health were hard to ﬁ  nd.(11) Since then, there 
has been an increasing use of the so-called cost-per-QALY approach in mental health evaluations, following recommendations for such analyses by regulatory bodies in Australia, Canada, the United Kingdom, and the United States. In the ﬁ  eld of depression, for 
example, cost-utility analyses have now been carried out for: screening in primary care
(13) (annual and periodic screening cost

(13) (annual and periodic screening cost 
more than $50 000 per QALY, one-off screening below this thresh-old); newer versus older antidepressant drugs
(14); maintenance 
treatment for recurrent depression(15, 16) ; guideline-concordant 
primary care treatment for women(17); primary care practice-
initiated quality improvement programmes(18); computerized 
cognitive behavioural therapy(10); and ECT versus transcranial 
magnetic stimulation for ‘treatment-resistent’ depression.(19) Many 
of the cost-utility analyses carried out to date employ secondary data and modelling techniques to estimate costs and effects, others have constructed cost-per-QALY estimates alongside clinical trials.
An example of a cost-utility analysis using modelling is that 
by Revicki et al.
(14) who compared treatment for major depression

(14) who compared treatment for major depression 
with (a) newer antidepressants (nefazodone and fluoxetine) (b) tricyclics (imipramine) and, for treatment failures, (c) a step approach involving initial treatment with imipramine followed by nefazodone. A decision analysis model was developed to simulate the clinical management pathways and pattern of recurrences of major depression for these alternative treatment strategies to est imate 
lifetime medical costs and health outcomes (expressed as QALYs). There were only minor differences in costs and QALYs between 
nefazodone and ﬂ  uoxetine, and both these newer antidepressants 
were estimated to be cost-effective compared to imipramine treat-ment and the imipramine step approach. The ratios of cost to QALYs gained for these newer antidepressants were deemed to be sufﬁ ciently low (below $20 000 per QALY gained) to merit adop-

tion of these treatments in the health system. For example, the extra lifetime cost of nefazodone over imipramine ($1321) resulted in 0.32 added QALYs, giving a ratio of $4065 per QALY gained. Since decision models and their ﬁ  ndings are only as good as their under-
lying assumptions and the quality of the data used to estimate key 
model parameters, extensive sensitivity analyses were conducted, but these did not alter the conclusions. However, the results did not include indirect costs such as changes in work productivity—important for a societal perspective—and are not readily generaliz-able to groups other than the targeted population (in this study, 30-year old women with one previous depressive episode).
An example of the empirically based generation of cost-per-QALY 
information is the randomized controlled trial of practice-initiated quality improvement (QI) for depression,
(18) which involved

(18) which involved 
group-level randomization of 46 clinics in six community-based US managed care organizations, either to medication or psychotherapy quality improvement programme (in addition to training and enhanced educational resources). Two QALY measures were derived, one from the Short-From, 12-Item Health Survey (SF-12) plus a standard gamble utility weighting exercise among a local conve-nience sample, the other with reference to estimated time spent depressed plus values from the literature for lost utility due to depres-sion. Relative to usual care, average health care costs increased by $400–500 per treated patient, while QALY gains were less than 0.025, resulting in an estimated cost per QALY of $15 000–36 000 (QI-medication) and $9500–21 500 (QI-therapy). In addition to these health gains, patients exposed to the quality improvement pro-grammes were employed more days than those receiving usual care.
The envisaged beneﬁ  t of expressing the results of economic eval-

uation in these terms lies in the ability to line-up cost-per-QALY estimates for a range of different interventions and disorders, with a view to determining acceptable efﬁ  ciency against a pre-deﬁ  ned 
threshold (of, say, $50 000 in the US context), or even constructing ‘league tables’ summarizing best and worst buys in the health sector. In practice, there remain signiﬁ  cant problems in relying 
on league tables for allocating resources (due to the heterogeneous and context-speciﬁ  c nature of cost-utility studies), while there may 
be criteria unrelated to efﬁ  ciency that determine whether a partic-
ular intervention is deemed acceptable for reimbursement or inclusion in a deﬁ  ned package of basic health care.
Cost-effectiveness of interventions for child 
and adolescent mental health problems
There are hundreds of completed economic evaluations in the

There are hundreds of completed economic evaluations in the 
depression ﬁ  eld, almost all conﬁ  ned to adults of ‘working age’ . 
But there is surprisingly little economic evidence on child and adolescent mental health interventions. A systematic review a few years ago found only 14 published economic evaluations, some of rather poor quality.
(20) Common problems included small 
sample sizes, narrow cost measures, short follow-ups, and limited outcome measures. (Guidelines and quality checklists are available for health economist researchers and readers of their outputs.)
(21)

1477
Another drawback is that most of the completed economic studies 
have been undertaken in North America, the United Kingdom, and Australia. But the results of economic evaluations generally do not transfer easily from one health system to another because of differ-ences in system structure and ﬁ  nancing, leading to differences in rela-
tive costs. It is infeasible and certainly unnecessary to carry-out an evaluation every time a policy decision needs to be taken, but it is also difﬁ cult to assess the relevance of economic evidence from another 
country, especially if its mental health system is markedly different.
An example of a well-conducted cost-effectiveness analysis is the 
evaluation of a home-based social work intervention for children and adolescents who have deliberately poisoned themselves.
(22)

(22)
The researchers measured suicidal ideation, hopelessness, and fam-ily functioning as the main outcomes, and costs were based on pat-terns of utilization of health, education, social care, and voluntary sector services. Within a randomized controlled trial, involving 162 children aged 16 years or under, they found no signiﬁ  cant 
difference in the main outcomes or costs, although parental satis-faction with treatment was signiﬁ  cantly greater in the group that 
received a new social work intervention compared to those who received routine care.
In another pragmatic randomized trial, a parenting intervention

In another pragmatic randomized trial, a parenting intervention 
for parents of children at risk of developing conduct disorder (the Incredible Y ears programme) was compared to wait-list controls. The perspective for cost measurement was the public sector (health, social care, special education); effectiveness was measured by 
reductions in intensity of behaviour problems.
(23) The Incredible 
Y ears programme was more effective but also more costly. The researchers found that it would cost £1344 to bring the average child in the intervention group (in terms of behaviour intensity score) to below the clinical cut-off point. A cost-effectiveness acceptability curve was plotted to show the trade-offs between cost and effectiveness.
Sectoral cost-effectiveness analysis of 
mental health interventions in developing countries
Cost-effectiveness analysis can also be used to evaluate mental

Cost-effectiveness analysis can also be used to evaluate mental 
health programmes for whole populations (countries or even world regions). While the burden of neuropsychiatric disease is very high, the resources available to address that burden are extremely low. Given the consequent tension between the need for and the availability of mental health care, plus the fact that effective inter-ventions do exist, the job of cost-effectiveness analysis is to show how much of the burden can be reduced or averted, by doing what, and at what cost.
Through its CHOICE project (choosing interventions that 
are cost-effective), WHO embarked on an initiative to assemble databases on cost-effectiveness of key health interventions in 14 epidemiological sub-regions of the world.
(24) A comparative 
cost-effectiveness analysis of interventions for reducing the burden

cost-effectiveness analysis of interventions for reducing the burden 
of major neuropsychiatric disorders formed part of this pro-gramme.
(6, 25, 26)  WHO-CHOICE advocates a ‘generalized’ form of 
cost-effectiveness analysis, in which costs and effects of current and new interventions are compared to the starting point of ‘doing nothing’ . Accordingly, the costs and effectiveness of pharmacologi-cal and psychosocial interventions in primary care or outpatient settings for psychiatric disorders were compared in a population 
model to an epidemiological situation representing the untreated natural history of these disorders. Effects are measured as disability adjusted life years (DALYs) averted (i.e. reduced burden), and costs in international dollars (I$; one international dollar should buy the same quantity of health care resources in China as in the United States).
Compared to no treatment (natural history), the most cost-

effective strategy for averting the burden of psychosis and severe affective disorders in developing regions of the world is a combined intervention of ﬁ  rst-generation antipsychotic or mood-stabilizing 
drugs with adjuvant psychosocial treatment delivered by 
community-based outpatient services, with cost-effectiveness ratio of I$4200–5500 in Sub-Saharan Africa and South Asia, rising to more than I$10 000 in middle-income regions
(25) (see Fig. 7.7.1). 
Currently, the high acquisition price of second-generation antipsy-chotic drugs makes their use in developing regions questionable on efﬁ ciency grounds alone, although this situation stands to change 
as these drugs come off patent. By contrast, evidence indicates that the relatively modest additional cost of adjuvant psychosocial treatment reaps signiﬁ  cant health gains, thereby making such a

as these drugs come off patent. By contrast, evidence indicates that the relatively modest additional cost of adjuvant psychosocial treatment reaps signiﬁ  cant health gains, thereby making such a 
combined strategy for schizophrenia and bipolar disorder treat-ment more cost-effective than pharmacotherapy alone.
For more common mental disorders treated in primary care settings 
(depressive and anxiety disorders), the single most cost-effective strategy is the scaled-up use of older antidepressants (due to their lower cost but broadly similar efﬁ  cacy to newer antidepressants). 
However, as the price margin between older and generic newer antidepressants continues to narrow, generic SSRIs should be at 
least as cost-effective and may therefore represent the treatment of

least as cost-effective and may therefore represent the treatment of 
choice in the future. Since depression is commonly recurring, there are also grounds for thinking that proactive care management, including long-term maintenance treatment with antidepressant drugs, represents a cost-effective (if more resource-intensive) way of signiﬁ  cantly reducing the enormous burden of depression in 
developing regions.
(27)
The purpose of such an exercise is to locate the relative position 
of effective and applicable interventions within a wider cost-effectiveness and priority-setting framework. Using the affordabil-ity criteria of the WHO Commission for Macroeconomics and Health,
(28) this analysis indicates that (a) the most efﬁ  cient inter-

ventions for common mental disorders can be considered very cost-effective (each DALY averted costs less than 1 year of average per capita income), and (b) community-based interventions for severe mental disorders using older antipsychotic and mood-stabilizer drugs meet the criterion for being cost-effective (each DALY averted costs less than three times GDP per capita). These ﬁ ndings therefore provide relevant information regarding the 
relative value of investing in neuropsychiatric treatment and prevention, and so may help to remove one of many remaining barriers to a more appropriate public health response to mental 
health needs.
Economic evaluation provides a means of comparing the costs and outcomes of mental health interventions or programmes, enabling

Economic evaluation provides a means of comparing the costs and outcomes of mental health interventions or programmes, enabling 
decision makers to assess whether they offer good use of (scarce) resources. An analysis of costs alone, or indeed of outcomes alone, 7.7 economic analysis of mental health services

SECTION 7  social psychiatry and service provision 1478
does not provide such information. The results of well-conducted 
economic evaluations can be channelled into decision-making processes at a succession of levels.
Patients, users, and caregivers
Economic evidence can complement clinical decision-making at the patient, user, and caregiver level by comparing costs and con-sequences of particular treatments. One very pertinent question about any treatment is whether the additional acquisition costs associated with (say) newer antidepressants or second-generation antipsychotics are compensated by better symptomatic response or fewer side effects. Our earlier examples of economic evaluations of treatments for depression and for child and adolescent mental health problems provide this kind of evidence.
Purchasers and providers
At another decision-making level, those who commission or purc hase

mental health services need economic data. A core element of local needs assessment and strategic service development by (say) a state health care system or a health maintenance organization concerns the resource implications of changes to, for instance, the hospital/community balance or investment in a new clinic or training of therapists.
Government and society
Economic evaluations should inﬂ  uence national-level policy and 
resource allocation decisions. Such evaluations have inﬂ  uenced 
policy with respect to the substitution of community-based for long-term hospital care, the development of ‘assertive outreach’ models, the expansion of early intervention initiatives for psychosis, and the overall level of funding. The CHOICE programme aims to provide this kind of evidence.
While adding economic analysis to mental health evaluations

While adding economic analysis to mental health evaluations 
introduces an extra dimension that offers a wider assessment of the implications of new or existing courses of action, there can also 
be limitations. Many economic evaluations fall short of the ideal, whether in terms of sample size, comprehensiveness of cost measurement, outcome assessment, or evidence interpretation. 
Conclusions based on small-sample randomized trials can often only be tentative, while failure to measure the wider (non-health 
and non-service) costs associated with two or more treatments may produce misleading and partial results.
Even when it overcomes these limitations, an economic evaluation 
can never resolve difﬁ  cult allocative and policy issues; rather, it is one 
additional tool that, together with evidence on the clinical and social dimensions, can facilitate explicit evidence-based decision-making.
Knapp, M.R.J., Funk, M., Curran, C., et al. (2006). Economic barriers to

Knapp, M.R.J., Funk, M., Curran, C., et al. (2006). Economic barriers to 
better mental health practice and policy. Health Policy and Planning ,
21, 157–70. http://heapol.oxfordjournals.org/cgi/content/
full/21/3/157
WHO. (2006). Dollars, DALYs and decisions: economic aspects of the mental 
health system . WHO, Geneva, Switzerland. http://www.who.int/
mental_health/evidence/dollars_dalys_and_decisions.pdf
Website of WHO’s cost-effectiveness work programme (CHOICE): 
http://www.who.int/choice
1. WHO. (2001). The World health report 2001; mental health: new 
understanding, new hope . WHO, Geneva.
2. WHO. (2004). Mental health policy, plans and programmes. Mental health 
policy and service guidance package . WHO, Geneva.
3. WHO. (2000). The world health report 2000; health systems; improving 
performance . World Health Organization, Geneva.
4. Dixon, A., McDaid, D., Knapp, M., et al.  (2006). Financing mental health

4. Dixon, A., McDaid, D., Knapp, M., et al.  (2006). Financing mental health 
services in low- and middle-income countries. Health Policy and Planning ,21, 171–82.Fig. 7.7.1 Cost-effectiveness ratios 
for a basic mental health package in 
low and middle-income regions of the world. 02,0004,0006,0008,00010,00012,000Cost per DALY averted (international dollars)
Sub-Saharan
AfricaLatin America &
CaribbeanMiddle East &
North AfricaEurope &
Central AsiaSouth
AsiaEast Asia &
PacificDepression : Older antidepressants +
psychosocial Tx
Panic disorder : Older antidepressants +
Schizophrenia : Older antipsychotic drug +
Bipolar disorder : Older mood stabiliser +

1479
 5. Knapp, M.R.J., Funk, M., Curran, C., et al.  (2006). Economic barriers 
to better mental health practice and policy. Health Policy and Planning ,
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 6. WHO. (2006). Dollars, DALYs and decisions: economic aspects of the 
mental health system . WHO, Geneva.
 7. Scott, S., Knapp, M., Henderson, J., et al. (2001). Financial cost of 
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interventions. In Measuring mental health needs  (2nd edn) (eds. 
G. Thornicroft, C. Brewin, and J.K. Wing), pp. 200–24. Gaskell, London.
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10. McCrone, P ., Knapp, M., Proudfoot, J., et al. (2004). Cost-effectiveness 
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11. Chisholm, D., Healey, A., and Knapp, M.R.J. (1997). QALYs and 
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14. Revicki, D., Brown, R., Keller, M., et al.  (1997). Cost-effectiveness of 
newer antidepressants compared with tricyclic antidepressants in managed care settings. The Journal of Clinical Psychiatry ,58, 47–58.

15. Kamlet, M.S., Wade, M., Kupfer, D.J., et al.  (1992). Cost-utility analysis 
of maintenance treatment for recurrent depression: a theoretical 
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16. Hatziandreu, E.J., Brown, R.E., Revicki, D.A., et al. (1994). Cost-utility 
of maintenance treatment of recurrent depression with sertraline 
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primary care intervention for depressed females. Journal of Affective 
Disorders ,74, 23–32.18. Schoenbaum, M., Unutzer, J., Sherbourne, C., et al. (2001). 
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22. Byford, S., Harrington, R., T orgerson, D., et al. (1999). 
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of Psychiatry ,174, 56–62.
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choices in health: WHO guide to cost-effectiveness analysis . WHO, 
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psychiatry. World Psychiatry ,4, 37–44.
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(eds. D. Jamison, J. Breman, A. Measham, et al.). Oxford University 
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and health: investing in health for economic development . WHO, 
Geneva. 7.7 economic analysis of mental health services

7.8
Psychiatry in primary care
David Goldberg, André Tylee, 
and Paul Walters
In recent years, major epidemiological surveys have been carried 
out in the community in many different countries, in the United Kingdom most recently by the Ofﬁ  ce of National Statistics (to ﬁ  nd 
this and other surveys go to http://www.statistics.gov.uk/STATBASE/Product.asp?vlnk=8258). The ﬁ  ndings in such com-
munity surveys can be compared with ﬁ  ndings in primary care

munity surveys can be compared with ﬁ  ndings in primary care 
surveys, when it will be found that the list of common mental dis-orders is not quite the same, although conditions characterized by symptoms of depression and anxiety are the most common. Rather than considering the detailed diagnoses, it can be helpful to distin-guish between ‘internalizing disorders’ , which besides anxiety states and depression, also include the fear disorders like phobias and panic disorder, obsessive-compulsive disorder and many cases of somatization disorder; and ‘externalizing disorders’ consisting of conduct disorder in childhood, and antisocial behaviour, as well as drug and alcohol disorders in adult life. The former group of disorders are characterized by subjective distress, and typically high levels of anxious and depressive symptoms; while in the latter group abnormalities are in externally observed behaviour.
(1)
In community surveys it can be seen that rates of internalizing

(1)
In community surveys it can be seen that rates of internalizing 
disorders rise sharply after puberty, are highest between the ages of 35 and 55 and fall thereafter, and that females rates are higher than males at all ages., while rates of externalizing disorders reach their maximum between the ages of 15 and 34, and fall sharply after that, with males rates much higher than female rates at all ages. This is shown in Table 7.8.1 (which does not include antisocial behaviour as reliable data are not available in the community).
The Goldberg-Huxley Model(2)
This was devised as a framework for comparing the characteristics of patients seen in the community with those in other medical settings, and describing the pathway which people usually follow to mental health care in places where GPs act as ‘gatekeepers’ . It con-sists of ﬁ  ve levels, separated by four ﬁ  lters. The ﬁ  gures for psychiat-
ric morbidity over 1 year necessitate using estimates of incidence

ric morbidity over 1 year necessitate using estimates of incidence 
rates, and are therefore much higher than the point prevalence 
rates reported in community surveys. The essence of the model is the demonstration that most distressed patients will see a doctor over the course of 1 year (ﬁ  lter 1), but only about half of them will have their distress detected (filter 2). Most common mental 
disorders are treated in primary care, so ﬁ  lter 3 is relatively imper-
meable, only allowing one in five to pass. Psychiatrists only have any part in the process with the fourth ﬁ  lter, which also holds 
back most patients. Psychiatrists therefore form their ideas about mental disorders from a highly skewed section of all those with disorders.
Prevalence of psychiatric disorder in 
primary care
In the United Kingdom, about 80 per cent of the population consult 
their doctor in the course of a year, and prevalences among attenders are higher than among the general population.
(2) In con-

(2) In con-
trast, specialist mental health services see between 1 and 2 per cent of the population in the course of a year, and admit only about 0.5 per cent to inpatient care, so that primary care deals with the major part of the burden of common mental disorders.
The World Health Organization (WHO) carried out the largest 
primary care survey in 14 countries
(3) but for purposes of com-
parison only the UK data will be shown here. Table 7.8.2 compares the frequencies and types of mental disorders seen in the commu-
nity, in primary care, and in psychiatric practice. Mental disorders 
Table 7.8.1  Annual prevalence of mental disorders in the 
community by type and age, rates per 100 at risk
Disorder Gender 5 to 16 to 34 to 54 to 74 All (16–75)
Internalizing Male  3.1 11.70 16.75  9.87 13.5

Female  4.3 20.55 21.35 14.80 19.4
Externalizing Male 10.05 11.6; 18.9 2.25; 10.4 0.4; 3.8 6.0; 11.9
Female  4.35 5.3; 5.7 0.75; 2.1 0.4; 0.5 2.3; 2.9
Other Male  1.9  0.33  0.78  0.23  0.5
Female  0.75  0.42  0.73  0.52  0.6
Internalizing  = any neurotic disorder. Externalizing  = conduct disorder for age 5–16; for the 
remaining age groups the rate for drug dependence is shown ﬁ  rst, followed, after the semicolon, by the rate for alcohol dependence. Other  = psychotic disorders in adults. 
Source: National Statistics website: www.statistics.gov.uk Crown copyright material is reproduced with the permission of the Controller Ofﬁ  ce of Public Sector Information (OPSI).

1481
seen in primary care settings are more severe on average than those 
seen in community surveys, and different disorders predominate. The ﬁ  gures shown are for practices in Manchester with a fairly high 
prevalence of mental disorders, but the spread of diagnoses is fairly similar in other countries. The ICD-10 criteria only counted somatoform disorders if they were severe and long-standing, and do not count the many patients presenting with unexplained somatic symptoms, which are often accompanied by symptoms typical of anxiety or depression. A more recent study from Denmark
(4) has estimated that almost a half of their patients were

(4) has estimated that almost a half of their patients were 
diagnosed cases of mental disorders, with somatoform disorders being found in about one-third. Patients with established physical illnesses are also at greater risk of mental disorders, and this is especially so if they are disabled by their illness. It can be seen from Table 7.8.3 that disorders admitted to psychiatric hospitals in the United Kingdom are different again from those typically seen in primary care, with organic states, drug and alcohol dependence, schizophrenia and severe depressive states accounting for the majority of cases (Source: http://www.hesonline.nhs.uk/Ease/servlet/ContentServer?siteID=1937&categoryID=202).
A study in 10 European countries shows 28 per cent of consecutive 
attenders in the United Kingdom to be distressed on a screening interview, but only 6 per cent presented psychological symptoms 
to their GP . Most of these (5.5 per cent) received a psychiatric diag-

nosis, but the GPs also diagnosed others as ‘psychiatric’—so that their total rate was 15 per cent.
(5) These ﬁ  gures are fairly similar 
to those in Switzerland and the Netherlands, but in stark contrast to those in Eastern Europe. In the Russian Federation, for example, 27 per cent were distressed, but none reported psychological distress to their GPs, and none were diagnosed: however, the GPs identiﬁ  ed 3 per cent of their patients as ‘psychiatric’ . Fairly similar ﬁ gures were reported in Estonia, Poland, and Belgium; while 
ﬁ gures in Germany, Spain, and Sweden are intermediate ( ibid 2007; 
see Fig. 7.8.1). This study also showed that GPs who discuss psycho-social matters with their patients, and look at them are better at diagnosing them—a ﬁ  nding that echoes previous research in the 
United Kingdom.
(2)
It can be seen from Fig. 7.8.1 that most distressed patients—who

(2)
It can be seen from Fig. 7.8.1 that most distressed patients—who 
may well be found to have a mental disorder if interviewed with a research interview—do not mention their distress to their doctor, and that this accounts for failure to diagnose the disorder. Many patients who have not endorsed feelings of distress are nonetheless assessed as mental unwell, either because they are presenting with Table 7.8.2  Prevalence of mental disorder by gender for the community, for primary care attenders, and for admissions to psychiatric beds
The community annual prevalence (%) Primary care cases consecutive attenders (%) Mental hospital inpatients (%)
Males Females Males Females Males Females
Mixed anxiety depression  6.8 10.8  2.1  4.5  9.8 17.6
GAD  4.3  4.6  4.9 14.9Panic  0.7  0.7  3.4  3.6Phobias  1.3  2.2  2.1  4.6Neurasthenia – –  6.1 21.7
Somatoform disorder – – –  0.5

OCD  0.9  1.3 – –Depression  2.3  2.3 13.9 18.3 17.9 27.3Alcohol dependence 11.9  2.9  5.3  0.8Drugs dependence  5.4  2.1 – – 30.1 14.3Schizophrenia  0.6  0.5 – – 20.4 13.7Organic, dementia – – – – 10.3 15.9Subnormality – – – –  7.1  5.4
Developmental disorders – – – –  5.1  5.4
Any Dx 14.1% 19.9% 23.5% 27.5% 100% 100%
Sources: National Statistics website: www.statistics.gov.uk Crown copyright material is reproduced with the permission of the C ontroller Ofﬁ  ce of Public Sector Information (OPSI).
Table 7.8.3  The Goldberg-Huxley Model: Data for Manchester, UK
Level 1 : Community samples 250–315/1000/year
First Filter: The decision to consult
Level 2 : All those seeing GPs found to have a mental 
disorder210–230/1000/year
Second ﬁ  lter: GPs ability to detect

Level 3 : Cases recognized by the GP 101/1000/year
As ‘mental disorders’
Third ﬁ  lter: GPs decision to refer
Level 4 : All those seeing mental health professionals 20.6/1000/year
Fourth ﬁ  lter: Psychiatrist’s decision to admit to hospital
Level 5 : Those admitted as inpatients 3.4/1000/year
(Note that these estimates are annual period prevalences, and depend on estimates of 
annual incidence rates in addition to point prevalence rates. Source: Reproduced from D.P . Goldberg and P .J. Huxley, Common mental disorders—a bio-social mode l, 
copyright 1992, The Tavistock Institute, London.)7.8 psychiatry in primary care

SECTION 7  social psychiatry and service provision 1482
unexplained somatic symptoms or because they are under treat-
ment for a mental disorder that has responded to treatment.
Clinical presentations
Somatization is broadly deﬁ  ned as the expression of psychological 
distress through physical symptoms. In primary care, most patients present physical symptoms at the onset of an episode of anxiety and depression. This is actually the usual way that new episodes of common mental disorders present in general medical settings, as only about 15 per cent of new episodes present purely in psycho-logical terms.
(2)
Primary care somatizers can be subdivided into ‘facultative

(2)
Primary care somatizers can be subdivided into ‘facultative 
somatizers’ , who admit to their psychological symptoms and accept a mental disorder diagnosis if appropriately interviewed, and ‘pure somatizers’ who, despite such an enquiry, still deny the presence of psychiatric symptoms. People have many reasons for preferring to present somatic symptoms to their doctors—they are under-standably worried that they may have a new physical disease, they give priority to pains over other symptoms because it is pain that hurts, and they often wish to avoid the stigma of being thought psychologically distressed.
Somatizers may be compared with ‘psychologisers’ , who directly 
present their psychological problems to their doctors. The former are more likely to report adverse childhood events and periods of childhood illnesses, while the latter have more abnormal attach-
ment behaviours.
Hidden versus conspicuous morbidity
The ability of GPs to detect psychological disorders among their

The ability of GPs to detect psychological disorders among their 
patients forms the second ﬁ  lter that patients must pass through in 
order to receive a diagnostic label. This ability varies a good deal between places as well as between disorders. In the WHO study
(3)
the overall average detection rate was 48.9 per cent, but rates varied from 75 per cent for Verona to 15.9 per cent for Shanghai (62.9 per cent for Manchester). Recognition rates for individual diagnoses followed these overall rates, with somatization disorder 
being best recognized, followed by depression. However, these detection rates do not reveal whether the GP is identifying the same patients as the research assessment. In fact, the exact agreement between the two (measured by κ) is rather poor, at only +0.18 for 
all centres (+0.38 for Manchester).
The second ﬁ  lter is passed when the GP recognizes a mental

The second ﬁ  lter is passed when the GP recognizes a mental 
health problem in the patient, although this will often be without a precise ICD-10 diagnosis. Those recognized by the GP make up the ‘conspicuous’ morbidity —in fact, just under half of that estimated 
to be present in the waiting room population by a two-stage case-ﬁ nding procedure: so that the patients who are not identiﬁ  ed can 
be thought of as the ‘ hidden morbidity’ . These undetected patients 
continue to consult, but an outsider’s inspection of notes and prescriptions, or even discussion with the relevant doctor, will not identify them as patients with psychiatric morbidity. In practice, the ‘conspicuous’ morbidity may be greater than 50 per cent, as the longitudinal nature of primary care means that patients may be diagnosed in subsequent visits, and this is missed in cross-sectional waiting room studies.
(6,7) Kessler et al . followed up a cohort of

(6,7) Kessler et al . followed up a cohort of 
primary care patients over 3 years and found only 14 per cent of patients with depression remained unrecognized at the end of this period.
(8) Rost et al . followed up 98 depressed patients who 
had made at least one visit to their GP and found 32 per cent were undetected at 1 year.
(9) Despite this, GPs are good at recognizing 
severe depression, and unrecognized depression tends to be mild.
(10–12)  The severity of depression in primary care, rather than 
being deﬁ  ned categorically, may therefore be better conceptualized 
as running along a continuum from mild to severe. Using a dimen-sional approach Thompson et al . calculated GPs only miss one 
‘probable’ case of depression every 29 consultations.
(13)
Doctors better able to detect disorder have the following 
characteristics:(2)
◆ Make eye contact with the patient
◆ Make empathic comments
◆ Pick up verbal cues
◆ Pick up non-verbal cues

(13)
◆ Ask directive questions, with a psychological content
◆ Do not read notes, or look at their computer, while the patient 
is speaking
◆ Deal with over-talkativeness
◆ Deal with today’s problem
Data from the WHO study indicate that these ‘undetected 
illnesses’ are on an average less severe than those detected by GPs and have a somewhat better outlook. However, the data does not support the view that failure to detect these less severe disorders has serious long-term consequences for the patient
(14) although 
this does not mean that there are not individuals would be better served if their distress was acknowledged.

Mental illness in the elderly is common in primary care. Between 5 and 10 per cent of older adults attending primary care will suffer from depression, though this may be higher in areas of socio-economic Fig. 7.8.1 Proportions of population that feel distressed, present symptoms of 
distress, are diagnosed if they do so, and total number of patients diagnosed, in 10 European countries (Reproduced from P . Verhaak, J. Bensing, and A. Brink-Nuinen, Primary mental health care in 10 European countries: patients’ demands and 
GPs’ responses. European Journal of Psychiatry , 21, (1), Zaragoza Jan–Mar 2007, 
copyright 2007, INO REPRODUCCIONES, S.A.).051015202530
BeEst Ger NethPo Ru SpSwe Swi UK
All countries
% feels distressed % presents symptoms
% with sympt. + diagn % diagnosed total

1483
deprivation.(15) Older people are less likely to admit to psychiatric 
problems and more likely to emphasize somatic concerns and pres-ent behavioural changes. One study found that only 38 per cent of those identiﬁ  ed as depressed through screening in the commu-
nity had discussed feelings of depression with their GP .
(16)
This may lead to under-recognition in primary care. Crawford et al . found that only 52 per cent of 62 patients identiﬁ  ed with 
clinical depression from a community survey were correctly diag-nosed by their GP .
(17) The elderly may attribute their symptoms 
to ‘normal ageing’ , grief, or physical illness, or may fear sigmatization more than younger patients making recognition more difﬁ  cult. Elderly depressed men may be particularly likely to 
go unrecognized.
(17)
A systematic approach using a collaborative care model may

(17)
A systematic approach using a collaborative care model may 
improve depression management for the elderly in primary care. The Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial in the United States demonstrated that a primary care collaborative model for late-life depression was more effective than usual care in improving depressive symptoms. It also decreased pain due to osteoarthritis, increased functional abilities, and improved quality of life.
(18) The collaborative care model was highly 
cost-effective(19) and continued to show beneﬁ  ts over a 2-year 
follow-up period.(20)
The other major condition with which the GP will be involved 
is dementia. In the United Kingdom, the prevalence rate is approximately 5 per cent for all those over 65, but there is an age-related rise within this band to 25 per cent for those aged over 85. Consultations for organic psychoses reﬂ  ect this: 370 consultations

per 10 000 years at risk for those aged over 75, and 888 per 10 000 years at risk for those aged over 85. However, the management of people with dementia in primary care has been criticized.
(21) Up to 
75 per cent of patients with moderate to severe dementia and up to 97 per cent of patients with mild cognitive impairment go unrec-ognized by their GP .
(22) Again there may be a number of reasons 
for this. Dementias have an insidious onset, and sometimes the doctor’s familiarity with the patient can militate against spotting change. If a relative also accepts that the changes associated with dementia reﬂ  ect normal ageing, the diagnosis may be delayed or 
never made. Only 40 per cent of GPs in the United Kingdom use a speciﬁ  c test to detect dementia, and in a survey of 8051 GPs in 
England 40 per cent thought an early diagnosis of dementia was not important.
(23) Turner et al . surveyed GPs knowledge, conﬁ  -

dence, and attitudes about dementia and found that despite GPs overall knowledge about diagnosis and management being good, a third lacked conﬁ  dence in their diagnostic skills and two-thirds 
lacked conﬁ  dence in their management of behavioural problems 
and other associated problems in dementia.
(24)
Downs and others conducted a trial of an educational package to 
improve detection and management of dementia in primary care.(25)
In the United States, a trial of collaborative care versus care as usual for patients with dementia in primary care has produced encouraging results.
(26) Compared with care as usual, collaborative

(26) Compared with care as usual, collaborative 
care (consisting of case management though a senior practice nurse working with the patient’s family and integrated in the pri-mary care team, and the use of standard protocols to guide and monitor treatment) resulted in signiﬁ  cant improvements in the 
quality of care and in the symptoms of dementia, without an increase in psychotropic medication use.Classiﬁ  cation of mental disorders in 
Difﬁ culties with conventional psychiatric taxonomies
The main problem with the International Classiﬁ  cation of Diseases, 
10th Edition (ICD-10)(27) or Diagnostic and Statistical Manual, 
4th Edition (DSM-IV)(28) classiﬁ  cations used by psychiatrists is

4th Edition (DSM-IV)(28) classiﬁ  cations used by psychiatrists is 
that they were devised to describe a very different consulting population, they are needlessly complicated, and they do not lead directly to management. Patients usually present a mixture of physi-cal, psychological, and social symptoms expressed in any order, although somatic symptoms are usually ﬁ  rst. Some symptoms 
are repeatedly mentioned and some are mentioned only in passing. Symptoms left to the end may be the most important of all. Symptoms may not ﬁ  t a psychiatrist’s taxonomy. In primary care, 
patients often have several concurrent problems of a medical, psychological, and social nature.
Most psychologically distressed patients show symptoms of 
both anxiety and depression. The ICD-10 classiﬁ  cation has a mild 
disorder called ‘mixed anxiety depression’ , since some patients have

disorder called ‘mixed anxiety depression’ , since some patients have 
symptoms of each which together seem sufﬁ  cient for a diagnosis, 
although not satisfying the criterion for either disorder on its own. However, this does not solve the problem of the many patients who are above the threshold for both disorders, who are declared ‘co-morbid’ for two different disorders by conventional psychiatric taxonomy.
An alternative view points out that the two groups of symptoms 
are strongly correlated with one another (about +0.7) in the con-sulting population,
(2) and thus views them as two related dimen-

sions of symptomatology which tend to co-vary over time. GPs themselves rarely emphasize the distinction between the two groups of symptoms, and there appears to be no evidence that any adverse consequences follow this neglect. For the GP , the diagnostic task can be one of separating the symptoms of depression and anxiety from those of an accompanying physical illness, or of probing for psychiatric morbidity in patients where apparent physical symptoms do not have an organic cause. In primary care settings, ‘co-morbidity’ refers to patients who have both physical disorders and mental disorders.
Solutions to the classiﬁ  cation problem
Both the major psychiatric classiﬁ  cations—ICD-10 and DSM-IV—

offer special versions produced in collaboration with primary care physicians which are deemed suitable for this setting, and roughly 
correspond to the parent classiﬁ  cation. The WHO offers ‘ ICD10-
PHC ’
(29) which consists of 26 common conditions, with advice on 
how they present, the diagnostic features, the differential diagnosis of similar symptoms, essential information for the patient and the carer, advice and support for the patient and the carer, the role of medication, and indications for referral to the mental health services. Information is given about national organizations, and self-help materials, to assist people with particular diagnoses, and advice is given to GPs in particular areas about customizing the system by including information about self-help and support groups for local people.
The ‘ DSM-IVPC ’
(30) on the other hand is organized by symptoms

(30) on the other hand is organized by symptoms 
that branch out into diagnostic algorithms. The GP assesses the 7.8 psychiatry in primary care

SECTION 7  social psychiatry and service provision 1484
patient’s symptoms and, in workbook fashion, determines the 
relevant psychiatric diagnoses. The manual is formatted to be con-cise and practical, with limited use of psychiatric jargon. As a key feature, the chapter devoted to ‘Algorithms for Common Primary Care Presentations’ presents nine algorithms, headed by the presenting symptoms, for the most common psychiatric concerns encountered in primary care. No advice is given on management or on information to be given to carers.
Given the quantity of printed material that ﬂ  oods into GPs ofﬁ  ces,

Given the quantity of printed material that ﬂ  oods into GPs ofﬁ  ces, 
it is doubtful whether many GPs keep such systems on their desks—although they may be incorporated in their computer programs. It is more realistic to use such systems in training new doctors, so that ways of approaching patients and their carers become incorporated in their usual routines, with the system only consulted when an unusual problem presents itself. It can be seen that whereas the DSM-IV sys-tem is aimed at formal diagnosis, the ICD10-PHC system is aimed at management once an assessment has been completed.
The International Classiﬁ  cation for Primary 
Care, (ICPC -2-R)(31)
The classiﬁ  cation most widely used by GPs is of course their own, 
devised under the auspices of the World Organization of National Colleges & Academies (‘WONCA ’), called the International Classiﬁ  cation for Primary Care, ‘ ICPC-2-R ’ . This is a system which

devised under the auspices of the World Organization of National Colleges & Academies (‘WONCA ’), called the International Classiﬁ  cation for Primary Care, ‘ ICPC-2-R ’ . This is a system which 
classiﬁ  es all patient data and clinical activity in primary care, taking 
into account the frequency distribution of problems commonly encountered.
It allows classiﬁ  cation of
◆ the patient’s reason for encounter (RFE),
◆ the problems/diagnosis managed,
◆ interventions,
◆ test results, and the
◆ ordering of these data in an episode of care structure
It has a biaxial structure and consists of 17 chapters, each divided 
into seven components dealing with
◆ symptoms and complaints
◆ diagnostic, screening, and preventive procedures
◆ medication, treatment, and procedures
◆ test results
◆ administrative
◆ referrals and other reasons for encounter, and
◆ diseases
It is not clear to what extent all GPs work their way through this

◆ diseases
It is not clear to what extent all GPs work their way through this 
complex system, but should they reach the seventh component, there is a rough correspondence with the ICD. Note that multiple disorders can be coded in the same episode, but the extent to which 
this is done is not clear. Nor does the system provide advice on the 
management of the various conditions—it is assumed that the 
clinician knows how to do this.
The Read codes(32)
The most widely used system in the United Kingdom since the advent of computerization, are the Read codes. This meets the needs of the generalist by including diagnoses, symptoms, and 
problems. Some very broad reasons for consultation—such as ‘anx-
iousness’ , ‘depressed’ , and ‘headache’ are provided. A letter of the

iousness’ , ‘depressed’ , and ‘headache’ are provided. A letter of the 
alphabet is followed by up to four numerical codes, and there are also about 50 codes for diagnoses such as E204. ‘Depression’ or E2003 ‘anxiety with depression’ , which correspond very roughly to ICD diagnoses. However, no criteria are given, nor any advice on management for these various diagnoses.
None of the above four systems take into account functional 
impairment and disability, yet clinicians need to consider this in conjunction with the set of symptoms presented by an individual patient. Both diagnosis and current impairment are essential, and may help to explain why up to a quarter of patients with schizo-phrenia are managed solely in primary care settings
(33) whilst some 
patients with adjustment disorder need referral to the community mental health team.
Improving the identiﬁ  cation of some 
common disorders

(a) Aids to accurate detection of depression
Rather than using routine screening questionnaires to all patients, 
it is more practical to ask the following questions in six groups of patients:
◆ all those who look or sound depressed, or mention depressive 
symptoms
◆ all those with a past history of depression
◆ all those with signiﬁ  cant physical illness causing disability
◆ all those with diabetes and coronary heart disease, where the risk 
is higher
◆ all those with other mental health problems, such as dementia or 
heavy drinking
◆ mothers of infants who are either single or are unsupported by a 
partner or family
Both these questions should be asked:
◆ During the past month, have you been feeling down, depressed 
or hopeless?
◆ During the last month, have you often been bothered by having

◆ During the last month, have you often been bothered by having 
little interest or pleasure in doing things?
(b) Aids to accurate assessment of severity of depression
If positive replies are obtained to either of these, assess severity of 
using the Patient Health Questionnaire-9 (PHQ-9) a questionnaire 
with nine questions validated for use in primary care,(34) which 
may assist in ensuring that antidepressant medication is better tar-geted on those with moderate and severe degrees of depression.
(c) Aids to the accurate detection of alcohol problems
Other, more recent tools, such as the Drug Abuse Problem Assessment for Primary Care (DAPA-PC),
(35) were designed spe-
ciﬁ cally to be administered via computer. While currently popular

ciﬁ cally to be administered via computer. While currently popular 
in the areas of depression and substance abuse, the audience for assessment tools is expanding for a number of reasons, including: convenience, privacy, high-patient satisfaction,
(36) decreased pro-
vider time, improved validity, and reliability,(37) and decreased 
expense.

1485
The management of mental disorders within 
(a) Stepped care
With the introduction of mental health guidelines there has been 
a shift towards stepped care for mental health problems.(38) Stepped 
care ‘provides a framework in which to organize the provision of services supporting both patients and carers, and healthcare pro-fessionals in identifying and accessing the most effective interven-tions’ (see Fig. 7.8.2). Stepped care allows treatment to be provided in steps according to the severity of problems and/or response to treatment, aiming to provide the greatest beneﬁ  t to most of the

people from the resources available. Patients who fail to respond are given the next step on the treatment plan. Stepped care can be delivered by starting at the least invasive step and gradually ‘climbing’ the steps according to response, thus targeting more intensive treatments to those that that need them, or by ‘stratifying’ care so that the ﬁ  rst treatment step is determined by severity of 
disorder and thereafter by response.
(39) Stepped care was developed 
in the United States, initially for the management of depression.(40)
In the United Kingdom, this model of care has now been 
recommended for depression,(38) anxiety disorders,(41) obsessive-
compulsive disorder,(42) and self-harm.(43)
(b) Mental health workers based in primary care
Several new possibilities have emerged recently with the advent of the new graduate mental health workers  in primary care. The NHS

Several new possibilities have emerged recently with the advent of the new graduate mental health workers  in primary care. The NHS 
plan (DH 2000) was to have 1000 such workers in England and indications are that there are 600–700 in post. Mostly, the posts are similar to assistant psychologists and they generally are trained on a one-day release scheme at local university level in primary care 
mental health. Many are conducting initial assessment, providing brief psychological interventions such as brief cognitive behaviour therapy (CBT) or problem-solving for common mental health problems and medication management. Many are overseeing the use of self-help written materials and computerized help such as ‘Beating the Blues’ , a computerized CBT programme for depres-sion, which has been shown to be cost-effective.
(44) Graduate pri-

mary care mental health workers (PCMHWs) also act as advisors on the range of other local services (for example, local library bib-liotherapy schemes, and support groups). They have been proved to be effective at increasing patient satisfaction with episodes of care but were found not to improve mental health symptoms or to use the voluntary sector more than usual care.
(45) Many PCMHWs 
are psychology graduates, and they tend to move on after a year or two into much wanted clinical psychology posts, so corporate memory can be diminished. Many other interventions described in level two of the National Institute for Clinical Excellence (NICE) Depression guideline
(38) are increasingly applied in primary care—
such as exercise schemes, befriending schemes, brief problem-solving, brief CBT, self-help materials, and sleep restoration.
Practice primary care counsellors may in reality be psychologists,

Practice primary care counsellors may in reality be psychologists, 
psychotherapists, or counsellors depending on their training, expertise, and accreditation. They mostly see adults with common mental health disorders which may include adjustment disorders and losses. They often integrate different models of brief psycho-therapeutic treatment depe nding on their training and the particular
patient, and they receive regular supervision. These services may be provided in-house or in a neighbouring practice depending on 
Fig. 7.8.2 The stepped care model applied to depression. Reproduced with permission.(38) 
7.8 psychiatry in primary care

SECTION 7  social psychiatry and service provision 1486
available space. Some counsellors specialize in providing services 
for non-English speaking groups and certain patient subgroups such as eating disorders, domestic violence, etc.). Whilst resources are usually limited on occasions they may see patients for longer courses of treatment.
(c) The role of the primary care nurse
Practice nurses are increasingly involved in chronic disease man-agement within practices and this includes managing mental health conditions whether severe or common. From April 2006, practices have been rewarded in England under the Quality and Outcomes Framework of the General Services Medical Contract
(46) for screen-

ing their patients with coronary heart disease (CHD) and diabetes for depression and with any newly depressed patients for using a recommended patient self-report instrument to assess baseline severity of depression. The recommended instruments are the Patient Health Questionnaire-9 item (PHQ9),
(34) the Hospital 
Anxiety and Depression Scale (HADS),(47) or the Beck Depression 
Inventory (BDI).(48) Practice nurses are expected to undertake

Inventory (BDI).(48) Practice nurses are expected to undertake 
much of this work as they see the patients with CHD or diabetes for review and therefore they need proper training and supervision. Also rewarded in the GP contract is an annual physical review of all patients on the Severe and Enduring Mental Illness registers (SEMI or SMI)—again usually conducted by practice nurses. Such nurses have traditionally administered depot medication for such patients without much training on the procedure or the accompanying health checks. This training has been improving lately. Expecting an untrained practice nurse to administer depot without support and training is unacceptable, and training is needed in how to give the injection, how to review the suitability of this form of medica-tion, how to monitor for side-effects, how to assess mental state for signs of deterioration, when to involve colleagues or refer to the

community mental health team, and crisis management.
Practice nurses have been successfully trained in the assessment 
and management of depression
(49, 50) and the use of problem-
solving in major depression.(51) Practice nurses have been success-
fully trained in chronic disease management of the severely mentally ill,
(51) whereby they constructed a disease register, a care plan, and 
3-monthly structured reviews encompassing psychological, physical, and social well-being. Whilst the practice nurses were diligent and detected problems, there was little evidence that they communicated these to the GPs. There was also a failure to increase health promotion in this group, despite their recognized increased standardized mortality.
Health visitors trained in counselling have been shown to 
benefit women with postnatal depression,
(52) and Appleby 
et al.(53) have targeted the same group of patients with a nurse-led 
Primary care mental health services

The primary care team provides the majority of care to people suf-fering from mental health problems. Though many services remain GP-led, many are becoming increasingly sophisticated with a grow-ing number of professionals involved in the care of people with mental health problems. In England, the Department of Health has produced a guide for improving primary care mental health 
services.
(39)
A number of models for primary care mental health services 
are described reﬂ  ecting the need for services to provide care to populations with different needs, resource availability, and rela-
tionships with secondary care. Examples include the ‘opt-in’ or self-referral model, proactive models such as a collaborative care model, ‘one-stop shop’ models, and focused service models (i.e.

tionships with secondary care. Examples include the ‘opt-in’ or self-referral model, proactive models such as a collaborative care model, ‘one-stop shop’ models, and focused service models (i.e. 
services are developed for a speciﬁ  c remit such as common mental 
disorder or psychosis). The ‘opt-in’ model is one in which the patient initiates care and follow-up and is the traditional primary care model. In a collaborative care model there is active follow-up and collaboration between patient, primary care health profession-als, and when required secondary care professional with the health professional coordinating care. A ‘one-stop shop’ model provides a single point of access to all mental health services with a triage system determining resource allocation. There is no perfect model, and all have advantages and disadvantages depending on the popu-lation needs and availability of resources.
As services develop so the range of primary care mental

As services develop so the range of primary care mental 
health professionals is expanding. As well as the traditional primary care professionals—the GP and practice nurse—many practices now have others, including primary care graduate mental health workers and health visitors. Their roles include making assess-ments, facilitating referrals and movement through the health care system, and delivering treatments. In the United Kingdom, the availability of counselling services is now commonplace in primary care and up to 50 per cent of general practices have on-site counselors.
(54) They are referred people with a wide range

(54) They are referred people with a wide range 
of common mental disorders and other psychosocial problems such as adjustment disorders. Bower and Roland reviewed the evidence for the effectiveness of counselling in primary care and found it was associated with a modest improvement in short-term outcomes compared to usual care, but was no better than usual care over the longer-term. It did not appear to be any more cost-effective than usual care but patients appeared satisfied with it.
(55)
The primary–secondary care interface
What GPs expect of psychiatrists

(55)
GPs expect psychiatrists to possess and exhibit specialized skills of assessment and management not possessed within the primary health care team. The primary care team may include primary care mental health workers ranging from graduate workers to counsel-lors, psychotherapists, or psychologists, although if present these are usually extremely thinly spread (i.e. 1–2 sessions per practice per week). GPs do expect their psychiatrists or a named person from the mental health team to be available when they are needed, and they should also make themselves available for incoming telephone calls from the key contact. Because of sheer numbers (in England and Wales there are 12 times as many GPs as psychiatrists) the GP must protect this valuable resource by not overloading it with inappropriate referrals and by obtaining and maintaining certain assessment and management skills that can be used in pri-

mary care as well as sharing the care of certain patients under the 
leadership of secondary care. Referrals will vary widely from prac-tices depending on their own ‘in-house’ expertise and the presence or absence of any primary care mental health workers or local counselling services. Larger practices often have more in-house 
expertise and are more likely to have at least one of their GPs who 
possess more specialized mental health skills. Small practices with one or two partners are less likely to have such skills and may need

1487
more support. GPs expect the psychiatrist to provide inpatient care 
when needed (e.g. serious self-neglect, suicide intent, etc.) and day-patient facilities to provide a place of care, respite, and safety. They can also expect the psychiatrist to use diagnostic facilities and investigations (e.g. scans) as necessary and to provide highly spe-cialized treatments when indicated (e.g. electroconvulsive therapy). Less frequently, the GP may need respite from particular doctor–patient relationships for the longer-term good of both. Referral is also sometimes a result of pressure by the relatives or patient. Where good communication exists between primary and secondary care, these often ‘covert’ reasons for referral can be openly dis cussed.
Access to specialist assessment when appropriate is paramount

Access to specialist assessment when appropriate is paramount 
for a primary care service. GPs are not usually trained in specialist assessment and therefore, to match need to services, a psychiatrist, community psychiatric nurse, or psychologist from the community mental health team can perform this function, often in a primary care setting or the patient’s home. Other community mental health teams operate an outpatient clinic (which may be moved into the surgery). Often ‘true consultancy’ is being sought by the GP , whereby he or she may receive advice only. Other practices operate a joint consultation system whereby the specialist and generalist see the patient together and formulate a plan. With recent changes in the conﬁ  guration of mental health teams in the United Kingdom to

provide acute care, early intervention and assertive outreach, in some places the more traditional community mental health teams are being reduced which is often confusing and can be unsettling for practices which have developed relationships with individual 
psychiatrists and colleagues. Also, if crisis teams work 9 to 5 p.m., 
yet the GP surgeries are open until 6 or 7 p.m., this can create difﬁ culties for making urgent referrals.
Ways of organizing the interface
The interface between primary and secondary care is of key impor-
tance in the delivery of mental health care. Bower and Gilbody(56)

have described a continuum of specialist involvement in primary care mental health with least involvement of secondary care profes-sionals in the education/training model, and increasing involve-ment through the consultation-liaison model, the collaborative care and the replacement/referral model. In practice, these models are not mutually exclusive. They can complement one another and be adapted to take into account local workforce issues and staff availability.
There are at least four models of working across the interface 
between primary and secondary care:
1 A replacement/referral model  is the traditional way in which

1 A replacement/referral model  is the traditional way in which 
primary care interfaces with secondary care. In this model, the patient’s care is handed over to specialist services by way of a referral, the specialist service only relinquishing care when the patient had been treated. However, over the last 25 years other models have developed.
(57) These include:
2 The consultation-liaison model  allows secondary care profes-
sionals to develop ongoing relationships with primary care professionals, not only providing expert advice but also actively liaising with the primary care team, and often attending team meetings or seeing patients jointly with the GP .
3 The collaborative care model , as described above has primary

3 The collaborative care model , as described above has primary 
care mental health professionals working between primary and secondary care to improve the overall care of patients. These link-workers can provide active fo llow-up and acce ss to specialist 
advice and care as needed.
(59)
4 In the training/education model , secondary care provides 
education and training to the primary care team which otherwise 
functions autonomously utilizing secondary care services when needed via a referral system.
How health services negotiate the interface between primary 
and secondary mental health services is likely to get increasingly

and secondary mental health services is likely to get increasingly 
complex as secondary care moves away from centralized care through the community mental health teams, to specialist teams such as assessment and brief treatment teams, early intervention teams, and continuing care teams. It is likely that each of these teams will develop its own model of interfacing with primary care. This may allow for a more ﬂ  uid interface and closer working rela-
tionships between primary care and secondary care teams.
(59)
However, it needs to be managed appropriately or could lead to confusion of roles and responsibilities.
Shared care registers and shared care plans
Ashared care register  is usually a computerized record of all

Ashared care register  is usually a computerized record of all 
patients jointly cared for by the two services. It might consist of all those who have been discharged from hospital in the past 2 years, all those who have been on a psychotropic drugs for longer than a year, and all psychotic patients known to the GP who have not had an admission to the hospital. The record gives information about the key worker, outpatient clinics are held in the surgeries, and ‘good practice protocols’ can be developed, so that the case register can be audited against what other teams agree is good clinical practice.
Shared care plans  follow on from this development. Such a plan 
gives the primary care staff information about symptoms which they may expect while the patient is well, likely symptoms in relapse, the name of the key worker, and full details of whom to contact in an emergency both during the day and at night. The plan makes

clear who is responsible for medication, and gives an acceptable 
alternative should the GP ﬁ  nd it necessary to vary the medication. 
It is essential that these plans are mutually agreed between the two teams, rather than being imposed by one team on the other. GPs in England are now being remunerated for keeping registers of patients with psychotic illnesses, dementia, and learning disabilities.
Improving the mental health skills of GPs
About half of GP trainees have a 6-month psychiatry hospital attachment, many of which are considered to be unhelpful for a future generalist career.
(59) Many GPs have had no higher profes-

sional training in mental health and are not required to do so. There are several GPs who may have previously trained in psychia-try or psychotherapy (e.g. cognitive analytic psychotherapy, CBT, family therapy, etc.) before entering general practice and there is a growing national network of GPs with a special interest in psychiatry (GPsis) with the development of a national course for GPsis to Diploma/Masters level organized by PRIMHE, the National Primary Care Mental Health charity for professionals (www.primhe.org). The GPs network covers most regions and greatly overlaps with the National Trailblazer network (www.iop.kcl.ac.uk). Trailblazers was developed 10 years ago by one of the authors (AT) to bring together professionals from primary and secondary care to work together in pairs to build bridges and 7.8 psychiatry in primary care

SECTION 7  social psychiatry and service provision 1488
enhance local services by working on a local service development 
project together with supervision. Trailblazer courses bring pairs together for tutor and peer supervision of projects for up to a year. T o date nearly 1000 GPs, psychiatrists, CPNs, PNs, etc., have par-ticipated in this way and trailblazer training centres now run in every region in England, supported by the Regional Care Services Improvement Partnership Development Centres (www.csip.org.uk/regions) of the UK Department of Health. International trail-blazers is now part of the International Initiative for Mental Health Leaders (www.IIMHL.org) and runs in New Zealand, United States, and England where there is the added interest of comparing service systems by participants who have exchange visits as modules rotate in the three countries. Trailblazers has been positively evaluated for the adult-centred learning approach.
(60) Another well-recognized

(60) Another well-recognized 
Quality Improvement Programme with a long history of working in primary care has recently focused its methods on common mental health disorders. The Improvement Foundation (www.improvement foundation.org.uk) formerly known as the National Primary Care Development T eam (www.npdt.org.uk) have been working with 20 PCTs in England using a Plan Do Study Act cycle (PDSA) to help practices improve their depression care.
As there are few opportunities for primary care workers to obtain 
mental health skills training, one successful distance learning method involves the use of training DVDs. ‘Micro-skills’ of assess-ment or treatment of mental health disorders can be demonstrated by real-life general practitioners with actor–patients in 10 min consultations. The learner is then encouraged to practice these

skills using role-plays supplied with the DVDs. A series of existing training materials have been put together for the World Psychiatric Association (WPA) which involves two of the authors (DG and AT) and colleagues from the Institute of Psychiatry, and Prof. Linda Gask and her colleagues at Manchester University. The materials in this WPA package cover depression, somatization, chronic fatigue, schizophrenia, anxiety, and dementia (see www.iop.kcl.ac.uk or www.man.ac.uk for further details).
Summary
At one time, it was asserted that the ‘worried well’ were treated in primary care, while true mental illnesses were seen by the mental

Summary
At one time, it was asserted that the ‘worried well’ were treated in primary care, while true mental illnesses were seen by the mental 
illness services. This was not true when it was asserted, and is even less true now. The great majority of patients with common mental disorders are cared for within primary care, and many of those with severe mental illnesses are only seen in primary care. ‘Stepped care’ is a model for distributing clinical problems between the services, and ‘shared care’ refers to the care of patients seen by both primary care and specialist mental health services. Many other workers in primary care now assist GPs with the treatment of mental disorders, and special administrative arrangements within primary care are necessary to ensure that clinical services are available to those with special needs.
In summary, mental disorders in primary care:
◆ Are an important public health problem
◆ Frequently present with somatic symptoms

◆ Are more likely to be detected if the doctor has better communi-
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, 361–70.
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measuring depression. Archives of General Psychiatry ,4, 561–71.

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of depression. International Review of Psychiatry ,4, 311–6.
50. Mann, A.H., Blizard, R., Murray, J., et al. (1998). An evaluation of 
practice nurses working with general practitioners to treat people with depression. The British Journal of General Practice ,48, 875–9.
51. Mynors-Wallis, L.M., Gath, D.H., Lloyd-Thomas, A.R., et al. (1995). 
Randomised controlled trial comparing problem-solving treatment 
with amitriptyline and placebo for major depression in primary care. 
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general practice setting: controlled study of health visitor intervention in treatment of postnatal depression. British Medical Journal ,

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ﬂ uoxetine and cognitive-behavioural counselling in the treatment of 
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survey of counsellors in primary care: evidence for growing 
professionalisation . Royal College of General Practitioners, London.
55. Bower, P . and Rowland, N. (2006). Effectiveness and cost effectiveness 
of counselling in primary care.[update of Cochrane Database of Systematic Reviews, 2002; (1): CD001025; PMID: 11869583]. Cochrane 
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disorders in primary care: conceptual models and evidence base. British Medical Journal ,330, 839–42.

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evaluation of the Trailblazers teaching the teachers programme in mental health. Learning in Health and Social care ,2, 74–82.7.8 psychiatry in primary care

7.9
The role of the voluntary sector
What is the mental health voluntary sector?
The voluntary sector plays an important role in the mental health 
ﬁ eld across the world. Originally set up and run by volunteers, the 
prime motivation and purpose for this sector is improving the lives of people affected by mental health problems by doing things differently, tirelessly pushing for change, never giving up hope and working alongside service users (also known as patients and consumers) and their families every step of the way. In some coun-tries it has been labelled the ‘third sector’ to distinguish it from other organizational sectors namely industry (private sector) and government (public or statutory sector).
The voluntary sector is not, however, a cohesive group of 
organizations and across the mental health community each one operates with its own speciﬁ  c remit. Some of these organizations

organizations and across the mental health community each one operates with its own speciﬁ  c remit. Some of these organizations 
have become large businesses providing a wide range of services under contract with statutory agencies. Others choose to avoid 
employing staff and are still run entirely by committed volunteers. 
Many rely on voluntary donations in order to remain ﬁ  ercely 
independent of government. Each has its own aims and mission, core stakeholder group, trustee and membership structures, man-
agement systems, governance procedures, and a unique portfolio 
of activities.
Some mental health organizations focus activities on mental 
health or emotional well-being speciﬁ  cally (e.g. Finnish Association

health or emotional well-being speciﬁ  cally (e.g. Finnish Association 
for Mental Health). Others target a social problem and support all those affected such as charities working with the homeless, refu-gees, victims of domestic violence, or young offenders, including people with mental health problems. There are organizations that primarily campaign, educate, advocate, lobby, and promote self-help resources such as EUFAMI—an association for families across Europe and SANE Australia. In parts of the world, including Eastern Europe, there are particular challenges in mental health resulting from poverty, dislocation of the population, and insufﬁ  -

cient resources for health. Some states, like Armenia, have no mental health services. Here, the Catholic Agency for Overseas Development (CAFOD) is working with Armenia’s Association of Child Psychiatrists and Psychologists to provide therapy and men-tal health care and to increase awareness and understanding in order to overcome prejudice.
Wherever they work, key characteristics of voluntary sector 
organizations include an independent position, a strong values base, empowerment principles, non-proﬁ  t distributing of resources,

passionate commitment to the work focus, rooted to service user, and carer experiences and they are always striving for changes to provide people with mental health problems better provision and opportunities. Most started as local support groups but some have grown into large national organizations with considerable political leverage. The National Schizophrenia Fellowship (known today as Rethink) was founded in 1972 by a group of families con-cerned that relatives of people with schizophrenia had no support for themselves. In this chapter we draw on the Rethink experience to illustrate how the voluntary sector contributes to, and shapes, modern psychiatry. Although the English experience does not directly map onto those in other countries across the world, there are similarities and we seek to highlight these through the use of international examples where possible.
Rethink severe mental illness

Rethink is a membership charity with 7500 members (service users, carers, mental health professionals, the general public) whose mis-sion is ‘to support everyone affected by severe mental illness recover a better quality of life’ . It adopts a recovery-orientated approach to supporting the individual and their family through periods of ill health and their journey of recovery. This perspective is signiﬁ  cantly 
different from that of clinicians and statutory providers, who have not been through the experiences common to people who suddenly have to cope with severe mental illness. Rethink staff descriptions of their role include:
Bridging: linking a person with non-judgemental delivery of services connected with service user and carer experience
Ensuring service users are heard and needs met more holistically
Initially providing mutual support, the organization later offered 
information resources which address the problems commonly

information resources which address the problems commonly 
encountered by service users and carers, like difﬁ  culty in gaining 
access to services or funding for appropriate care. The emphasis is on ﬁ nding successful strategies which achieve solutions. Advocacy 
is provided for individuals and families whose needs are not being met. The experiences of service users struggling to cope provide detailed evidence which is used to develop Rethink’s policy on the mental health issues which reach the political arena and also as the basis of campaigns on stigma and discrimination. Research and

1491
surveys of service user and carer views form the basis of reports on 
vital issues, like how information can be provided to carers with due respect for the service user’s privacy and autonomy. Guidance on good practice may be developed and sometimes training for professionals. Media activity has publicized Rethink’s campaigns and using the internet has made dissemination of information cheaper and easier than it used to be.
Rethink’s activities also include the provision of front-line services 
in partnership with the National Health Service and Social Services (statutory sector) for example supported housing schemes, advocacy projects, community resource centres, carer support services, employment and training programmes, school education projects, and mentoring programmes for young people. In 2007, Rethink ran 350 front-line mental health services and employed approximately 1300 staff.
Does the voluntary sector 
make a difference?

The voluntary sector makes a substantial contribution to both the 
image of psychiatry and its practices. For example in New Zealand, the Mental Health Foundation has worked in partnership with the Ministry of Health and other agencies to run a successful anti-discrimination campaign—like minds, like mine (whakaitia te whakawhiu i te tangata) for the past 10 years. This is an internally renowned mental health awareness programme that is transform-ing how the New Zealand public engages with mental health issues. Non-Governmental Organizations (NGOs) can also bring inﬂ uence to bear at a national level and bring people together to 
plan new service models. The World Fellowship for Schizophrenia and Applied Disorders (WFSAD) supported a workshop in East Africa in 2003 where service users and families could meet with government ministers and medical professionals to discuss plans

for achieving effective health care delivery. In England, the volun-tary sector has collectively ensured that the published clinical guidelines describing best practice for the treatment of schizophre-
nia in 2002 took note of service user and carer treatment preferences. In India, Action for Mental Illness (ACMI), an advocacy initiative has achieved tax concessions for those with mental illness and their carers and also maintenance allowances equivalent to those provided to people with physical disabilities.
Standards of mental health care delivery vary dramatically—with

Standards of mental health care delivery vary dramatically—with 
cases of human rights abuses in psychiatry being documented in some countries and innovative services emerging in others in response to local demands. The voluntary sector can, and does, bring the spotlight on both ends of the service delivery spectrum (good and bad) and demand better for everyone. It also leads the way by developing innovative solutions both in terms of service delivery, public education, and self-management techniques. In the United States, NAMIs Peer-to-Peer Education Course is a 9-week experiential education course on the topic of recovery for anyone with serious mental illness who is interested in establishing and maintaining wellness. In Canada, a family to family network was established for ﬁ  rst episode psychosis families by the Canadian

Mental Health Association. The recovery model is being pioneered and embraced by the voluntary sector across the world. However, this relatively new approach requires a change of attitude by both service users and professionals as shown by the Scottish recovery network programme.Common themes tend to emerge through the campaigns of 
voluntary organizations across the world, in spite of differences in wealth and varying stages of development. In most places the demands are for earlier intervention, better crisis response, more support for families, and less use of physical restraint on the ward when coping with challenging behaviour. The transition to care in the community presented a new set of problems, not least the need for different professional skills and adequate resources. And in the 
later part of the last century, the controversy over community treat-

ment orders was raging in many countries. Changes in government policy and concerns over access to newer treatments resulted in new alliances in many countries, and the voluntary sector, clinicians and other professionals often learned to work together, recognizing how in alliance they could lobby more effectively for better law and more resources.
An excellent example of successful partnership working in 
England and Wales has been the formation of a coalition known as the Mental Health Alliance involving 80 organizations. Professional bodies have joined, including the Royal College of Psychiatrists as prominent and active members. The Mental Health Alliance has opposed the government’s proposals for reforming the Mental Health Act 1983 for the past 8 years and has managed to achieve some change in the content of the legislation as well as delaying the whole process.
The role of critical friends

The independence of organizations is an essential characteristic of the voluntary sector. These bodies do occupy the territory of ‘critical friends’ to both the statutory and private sectors of the mental health community, monitoring activity and speaking out in praise of positive developments but also highlighting when things are wrong.
For example at Rethink experience shows that misdiagnosis can 
result in inappropriate care and treatment with tragic consequences like imprisonment, suicide, or even homicide. Therefore Rethink supports service users in obtaining expert second opinions. Providing families or individual service users with accurate but understandable information enables them to challenge the opinion of a psychiatrist or medical team if this seems appropriate.
Rethink also advocates for families by using the complaints 
procedures or by providing legal representation at inquest hearings

procedures or by providing legal representation at inquest hearings 
in order to draw attention to deﬁ  ciencies in support, care, and 
treatment. They focus efforts on cases where systemic problems played a part, like a poor approach to risk assessment or refusal to accept information from families. The aim is to persuade the Ombudsmen or coroners to recommend improvements in the local policies and procedures in order to improve the quality of services.
In recent times there has been a spotlight on mental health 
services’ engagement with people from Black and Minority Ethnic groups (BME) in England. The BME voluntary mental health orga-nizations have formed a network which aims to reduce inequalities and promote good practice in mental health for racialized groups. The Network has been very critical of the Government’s proposals 
to amend mental health legislation and has criticized the statutory

to amend mental health legislation and has criticized the statutory 
health sector for failing to meet legal requirements on race equality. Similar issues arise in the United States where the National Council of La Raza (NCLR)—the largest national Hispanic civil rights and advocacy organization in the United States—works to improve 7.9 the role of the voluntary sector

SECTION 7  social psychiatry and service provision 1492
opportunities for Hispanic Americans. They report that Latinos are 
at a disproportionately high risk for depression and other condi-tions associated with mental illness, and are also much less likely to seek treatment or receive quality culturally and linguistically com-petent care.
The voluntary sector is a dynamic and vital part of any mental health system. Rooted in the experiences of mental health service users and carers, voluntary sector organizations across the world ensure that the voices of ‘experts by experience’ directly inﬂ  uence

campaigns, policy debates, service redesign, and project planning and treatment guidelines. The sector is, however, fragile and in some countries organizations are increasingly dependent on state funding which could undermine their autonomy and indepen-dence. Psychiatrists can support their local voluntary organizations by joining them—as members, as campaigners, and as educators. The sector can also support psychiatrists, helping to transform the public image of psychiatry and encouraging young people to take an interest in mental health as a career option. The alliances forged 
with psychiatrists and their representative bodies are crucial for improving the quality of mental health services and to effectively tackle stigma and discrimination. We do need each other in order to deliver better outcomes for mental health service users and their families.
The websites for some of the voluntary organizations referenced in the 
chapter are:

Rethink: www.rethink.orgCanadian Association for Mental Health: www.camh.ca
EUFAMI—European Federation of Associations of Families of People with 
Mental Illness: www.eufami.org
Mental Health Foundation in New Zealand: www.mentalhealth.org.nz
National Alliance on Mental Illness: www.nami.org
SANE Australia: www.sane.org
Scottish recovery network: www.scottishrecovery.net
The World Fellowship for Schizophrenia and Allied Disorders (WFSAD): 
www.world-schizophrenia.org

7.10
Special problems
Contents
 7.10.1 The special psychiatric problems of refugees
 7.10.2 Mental health services for homeless 
mentally ill people
Tom K. J. Craig
 7.10.3 Mental health services for ethnic minorities
Tom K. J. Craig and Dinesh Bhugra
7.10.1 The special psychiatric 
problems of refugees
While the forced displacement of people from their homes has 
been described since ancient times, the past half-century has witnessed an expansion in the size of refugee populations of extraordinary numbers.
(1,2) In 1970, for example, there were only 
2.5 million refugees receiving international protection, primarily through the United Nations High Commission for Refugees (UNHCR ). By 2006, UNHCR was legally responsible for 8.4 mil-

lion refugees. In addition, it is conservatively estimated that an additional 23.7 million people are displaced within the borders of their own countries. Although similar in characteristics to refugees who have crossed international borders, internally displaced per-sons do not receive the same protection of international law. Adding all refugee-type persons together, the world is forced to acknowl-edge the reality that over the past decade more than 10 000 people per day became refugees or internally displaced persons.
The sheer magnitude of the global refugee crisis, the resettlement 
of large numbers of refugees in modern industrial nations such as Canada, the United States, Europe, and Australia, and the increased media attention to civil and ethnic conﬂ  ict throughout the world

has contributed to the medical and mental health issues of refugees becoming an issue of global concern. This chapter will focus on a comprehensive overview of the psychiatric evaluation and treat-ment of refugees and refugee communities. Although this mental health specialty is in its infancy, many scientiﬁ  c advances have been 
made that can facilitate the successful psychiatric care of refugee patients.
Deﬁ nition
The deﬁ  nition of a refugee as outlined in the 1951 Convention 
and 1967 Protocol relating to the Status of Refugees is presented in Box 7.10.1.1.
(3) A person or persons who has passed over from one 
country into another seeking protection from violence and who cannot return to his country of origin because of fear of persecution or injury is considered a refugee according to inter-national law.
The 1951 Convention Relating to the Status of Refugees was

The 1951 Convention Relating to the Status of Refugees was 
drawn up by the United Nations parallel to the creation of UNHCR. This Convention and the subsequent 1967 Protocol establishes 
Box 7.10.1.1 Deﬁ  nations according to the 1951 convention and 
1967 protocol relating to the status of refugees
Article 1—Deﬁ  nition of the term ‘refugee’ A(2)  [Any person who] . . . 
owing to well-founded fear of being persecuted for reasons of race, religion, nationality, membership of particular social group or political opinion, is outside the country of his nationality and is unable or, owing to such fear, is unwilling to avail himself of the protection of that country; or who, not having nationality and 
being outside the country of his former habitual residence . . . , is unable or, owing to such fear, is unwilling to return to it. (As amended by Article 1(2) of the 1967 Protocol.)
Article 33—Prohibition of expulsion or return (refoulement)

Article 33—Prohibition of expulsion or return (refoulement) 
(1) No contracting state shall expel or return (refouler) a refugee 
in any manner whatsoever to the frontiers of territories where 
his life or freedom would be threatened on account of his race, religion, nationality, membership of a particular social group or political opinion.

SECTION 7  social psychiatry and service provision 1494
international law for the deﬁ  nition of refugees as well as the protec-
tion accorded to them. It also articulates the important principle of non-refoulement  (Box 7.10.1.1), which states that no refugee can be 
returned to his or her country of origin or any other location where there is any probability that he or she will be harmed. These legal deﬁ nitions indicate that a refugee is not an economic migrant or a 
traditional immigrant. Sadruddin Aga Khan, in a seminal report, was one of the ﬁ  rst High Commissioners to acknowledge the 
human rights violations that are primarily responsible for the generation of refugee populations.
(4) Corresponding to these inter-
national covenants, the international community has focused on the protection of refugees. There are two components to protection that are classically viewed by UNHCR as an essential aspect of its mandate. These two elements include protection against:

1 ongoing violence and potential injury to the refugee including 
being denied proper asylum and involuntary repatriation;
2 lack of adequate food, water, clothing, and other forms of mate-
rial assistance.
The UN Declaration of Human Rights adopted by the United 
Nations in December 1948 and the United Nations Convention against T orture and Other Cruel Inhuman or Degrading Treatment or Punishment adopted in December 1984 extends the basic prin-ciples of refugee protection and asylum, and reafﬁ  rms the principle 
of non-refoulement . In most refugee crises, not withstanding the 
political and military barriers to protection, UNHCR and the inter-national community strive to offer refugees a safe asylum and basic humanitarian aid.
Trauma and torture
By deﬁ  nition, most refugees have experienced traumatic life events

By deﬁ  nition, most refugees have experienced traumatic life events 
of extraordinary brutality. Since the Second World War, empirical studies have investigated the relationship between mass violence, the refugee experience, and psychiatric morbidity. The earliest research focused on survivors of the Nazi concentration camps.
(5–8)
Shortly after the Second World War, Eitinger and his colleagues gave a detailed account of their medical and psychiatric examina-tions of concentration camp survivors. They postulated that the traumatizing process had a dual nature. They described the somat-ic traumas of captivity, such as head injury, hunger, and infections, as leading to a ‘psycho-organic syndrome’ , and the predominately psychological traumas as leading to other psychiatric disorders such as depression. Thygesan’s studies of concentration camp survivors in Denmark revealed similar results.
(9, 10)  These early

(9, 10)  These early 
pioneering investigations of the psychosocial sequelae of the Nazi concentration camps established a preliminary baseline of trau-matic outcomes for future generations of refugees, many of whom had experienced the trauma of similar experiences in Cambodia, Bosnia-Herzegovina, and elsewhere.
Increasingly, civilian populations carry the burden of ethnic 
conﬂ  ict and mass violence. It is now estimated that more than 
80 per cent of casualties caused by the recent violence in Africa, Asia, and Europe have primarily affected non-combatants.
(11)
Extensive research has revealed the major trauma events experi-enced by refugee populations fall into the eight groups below:
1 material deprivation2 war-like conditions3 bodily injury
4 forced conﬁ  nement and coercion
5 forced to harm others
6 disappearance, death, or injury of loved ones7 witnessing violence to others8 brain injury
Every refugee situation will have a range of traumatic events that

Every refugee situation will have a range of traumatic events that 
will fall into each of these categories that are unique or characteristic of a speciﬁ  c conﬂ  ict. It is essential that the speciﬁ  c types of violence 
experienced by a given refugee population are well known to the psychiatric clinician who can use this knowledge to assess potential traumatic outcomes.
(12) In addition to many unique forms of 
violence occurring in different refugee settings, the meaning of violent events also differs across cultures. Anecdotal, clinical, and epidemiological evidence suggests that certain categories of refugee trauma are more potent than others in producing psychiatric morbidity and other traumatic outcomes. Brain injury, sexual violence, torture and other forms of bodily injury, coercion, and forced conﬁ  nement have great potential of causing psychiatric

harm in refugees exposed to these events. Consistent with indica-tors of the ‘potency’ of speciﬁ  c trauma events, there evidence of a 
dose–effect relationship between cumulative trauma and psychiat-ric symptoms.
(13) The personal aspects of human suffering associ-
ated with speciﬁ  c types of trauma, such as the murder of a child or 
the disappearance of a family member are still relatively undeﬁ  ned 
but obviously very difﬁ  cult.
Many refugees have actually experienced torture. Recent research 
states that the most signiﬁ  cant ﬁ  nding in the last 7 years may be 
that either torture has become more prevalent worldwide or the total number of events reported has increased, likely as a result of advocacy and elevated media attention.
(14) After 25 years of research 
on treatment work with torture survivors, still no consensus exists for effective interventions within the ﬁ  eld.
Conceptual model of traumatic outcomes

Research on refugees has revealed the persistence of negative health 
and social outcomes decades after their initial experience of violence and dislocation. Emergence of standardized criteria for psychiatric diagnoses and disability and the demonstrated ability to elicit trauma events through simple screening instruments in culturally diverse populations have allowed evidence to accumulate suggesting a model of traumatic outcomes associated with the refugee experience. This model is primarily based upon the classic epidemiological triad which describes the interaction between host (i.e. the refugee), agent (i.e. traumatic life experiences), and envi-ronment (e.g. refugee camp) in the pathogenesis of psychiatric dis-orders.
(15, 16)  This model, illustrated in Fig. 7.10.1.1, allows equal

(15, 16)  This model, illustrated in Fig. 7.10.1.1, allows equal 
attention to be given to all aspects of the refugee experience.
The model in Fig. 7.10.1.1 has three major elements. First, it sug-
gests that the major medical outcomes associated with the refugee experience are medical illness, psychiatric disorders, and disability. Second, trauma and the personal and environmental characteris-tics of the refugee describe the major risk factors associated with 
violent outcomes. Third, the direction of the causal arrows in the 
model do not imply a lack of reciprocal relationships where none is indicated; instead they indicate what most investigations consider

1495
to be the most dominant causal relationship. Despite its limita-
tions, this simple conceptual model can provide the psychiatric 
professional with a scheme for approaching the refugee patient 
from either a clinical or public health perspective. The importance 
of the socio-cultural and political context unique to each refugee 
situation and its impact on each of the model’s pathways cannot be 
overstated, since refugees come from diverse cultural groups and 
political experiences.
Health status and medical illness
Refugees experience many diseases and chronic debilitating 
conditions, such as starvation and landmine injuries that have 
both immediate and long-term effects on their physical health. 
Every refugee situation involves many unique but common acts of 
violence leading to major medical sequelae. For example, gender-
based violence and rape, which were instruments of ethnic cleans-
ing in the Balkans, resulted in pregnancy, medically complicated

ing in the Balkans, resulted in pregnancy, medically complicated 
self-administered abortions, and sexually transmitted diseases.(17)
Extensive documentation of refugee survivors of torture describes 
the medical sequelae of torture and the causal link between refugee 
trauma and medical mortality and morbidity over time.
Throughout the process of migration, refugees are frequently 
exposed to infectious diseases and physical or psychological trauma 
that can have a profound impact on their overall health and well-
being. Refugees are at increased risk for diseases such as obesity, 
diabetes, and heart disease, and often encounter signiﬁ  cant barriers 
to employment and health care when attempting resettle. For these 
reasons, programmes implemented in the refugees’ country of 
resettlement designed to improve health-seeking behaviours and

resettlement designed to improve health-seeking behaviours and 
overall self-care can have a positive, lasting impact on refugees’ 
physical and mental health.(18)
Psychiatric symptoms and illness
Observations since Kinzie et al .(19) and Mollica et al .(20) ﬁ rst 
diagnosed PTSD in Cambodian refugees, have made the cultural 
validity of PTSD seem almost certain. However, this reality does 
not negate the importance of culture-speciﬁ  c symptoms related to 
trauma that are independent of PTSD criteria. Recent large-scale 
epidemiological studies of refugee populations have conﬁ  rmed the high prevalence of major depression and PTSD in Western 
(e.g. Bosnian(21)) and non-Western (e.g. Cambodian(22) and 
Bhutanese(23)) refugee communities. The mental health impact of 
major depression, which presents both as a comorbid disorder with

major depression, which presents both as a comorbid disorder with 
PTSD and alone, is chronic, severely disabling and demands the 
attention of the clinician working with refugees. Longitudinal data 
indicates that 45 per cent of Bosnian refugees who met criteria for 
PTSD, depression or both continued to meet criteria for these dis-
orders 3 years later.(24) Similar results were found in a longitudinal 
study of Cambodian refugees 20 years after resettling in the United 
States.(25) As with Western populations, depression in refugees 
tends to be under-diagnosed and can be expressed as somatic com-
plaints. A study of Vietnamese refugees showed high prevalence 
based on self-report, but high rate of physician under-diagnosis. 
Most patients with depression (95 per cent) presented with physi-
cal complaints.(26) These ﬁ  nding underscore the importance of

cal complaints.(26) These ﬁ  nding underscore the importance of 
depression screening especially in the primary care setting.
New research indicates that there may be memory problems 
in refugees with PTSD. When asked to recall traumatic events 
refugees with PTSD reported an increased number of traumatic or 
torture events over their baseline report, as compared to those with 
other psychiatric disorders who showed no change or decreases in 
number of events reported.(27) Substance use disorders are often 
overlooked in refugee populations but are often comorbid with 
PTSD.(28) Early in the 1980s reports of Hmong refugees using 
opium emerged.(29) Substance use disorders have been shown to 
have a delayed presentation of 5 to 10 years after the initial settle-
ment of the refugee.(30) However, substance use disorders may vary

ment of the refugee.(30) However, substance use disorders may vary 
by population. One recent study of Cambodian refugees in the 
United States reports low rates of alcohol use in the past 30 days.(31)
Screening for substance use disorders especially in primary care is 
important. Complex grief reaction and chronic insomnia are also 
prevalent in this population.
(a) Head injury
Clinical evidence is also emerging identifying head injury as a cause 
of signiﬁ  cant psychopathology in refugee survivors. Head trauma 
is one of the most common forms of torture, so much so that 
reports of torture almost always imply that some kind of head 
trauma occurred. Many head injury survivors experience seizures 
and headaches, as well as behavioural disturbances such as aggres-
siveness, irritability, and sleep disturbances. Recent research on 
Vietnamese ex-political detainees who experienced head trauma

Vietnamese ex-political detainees who experienced head trauma 
while in captivity indicates that the number of head injuries is 
related to a decrease in executive functioning, those with head injury 
have increased risk of developing PTSD, and had decreased cortical 
thickness in several brain regions (Mollica et al. 2007, unpublished). 
The long-lasting effects of head trauma are serious and pervasive, 
affecting both the injured individual and their family. The presence 
of head trauma in torture victims has been overlooked in past 
research, but awareness is growing.
(b) Functional status and disability
Although the functional status of refugees at the emergency and 
long-term ends of the continuum of the refugee experience has 
received little attention, the signiﬁ  cance of this traumatic outcome

received little attention, the signiﬁ  cance of this traumatic outcome 
is beginning to emerge. Until recently, the standard operating 
model of refugee protection has not been asked to determine the 
long-term socio-economic damage caused by the refugee experi-
ence. The answer to this question is extremely important to the Fig. 7.10.1.1 Conceptual model of refugee risk factors and traumatic outcomes.
7.10.1  the special psychiatric problems of refugees

SECTION 7  social psychiatry and service provision 1496
recovery of societies in which the majority of the population has 
been displaced. In many societies, the refugee experience is the 
majority experience, which has strong implications for future 
socio-economic development. While the prevalence of functional 
impairment and disability is unknown in refugee populations, 
a recent epidemiological study of Bosnian refugees in Croatia 
reveals that functional disability may, in fact, be extremely high, 
especially in elderly refugees.(21) Furthermore, disability may be 
exacerbated in refugee survivors who have both chronic medical 
and psychiatric disorders.
This section reviews key factors unique to the psychiatric evalua-
tion and diagnosis of the refugee patient.
Primary care: the proper setting for a refugee clinic
The psychiatric literature has generally stressed the importance of 
evaluating and treating refugee patients in a primary health care

evaluating and treating refugee patients in a primary health care 
setting, whether in a refugee camp or in a country of resettlement. 
Four factors seem to support this viewpoint:
1 refugee patients seldom self-refer to psychiatry;
2 in many societies considerable stigma is associated with psychiatry 
but not with primary care medicine;
3 the majority of refugees seek out the care of their local medical 
doctors and indigenous traditional healers for the relief of their 
emotional suffering;
4 most refugees have associated medical and psychiatric disorders.
Considerable ﬁ  eld experience has shown that establishing a 
mental health programme within a health facility where refugees 
already seek medical care can result in the highly successful utiliza-
tion of psychiatric professionals and treatment.
Cross-cultural psychiatric assessment and diagnosis

Early research describing the psychiatric status of refugee survivors, 
especially those who had been tortured, refrained from the use of 
psychiatric diagnoses because of a prevailing perception that the 
observed symptoms were a normal response to horriﬁ  c life experi-
ences.(12) Similarly, many medical anthropologists believed that 
Western psychiatric diagnostic classiﬁ  cations were not relevant to 
the assessment of suffering in non-Western populations.(32) Despite 
these reservations, the emergence of standardized diagnostic criteria 
for major depression and post-traumatic stress disorder (PTSD) 
have allowed for the cultural validity of these diagnoses to be tested 
in a number of refugee settings. Cross-cultural research suggests 
that assessments of psychiatric illness should begin with phenom-

enological descriptions of folk diagnoses or culture-specific 
syndromes.(33) Important methods of exploring the validity of 
DSM-IV diagnoses in cross-cultural settings have included using 
culturally valid deﬁ  nitions of functioning and mental health prob-
lems based on local views of maladaptive thoughts and behaviour 
in response to distress, not preconceived Western diagnostic cate-
gories(34); however, to date, not a single culture-speciﬁ  c illness 
associated with the mass violence and torture experienced by 
refugees has been deﬁ  ned.(35) On the contrary, the criteria for the 
two major diagnoses associated with violence in Western society, 
i.e. major depression and PTSD, have been successfully applied to refugees from many parts of the world. While high rates of PTSD 
can be measured in refugee patients and traumatized civilians, it is

can be measured in refugee patients and traumatized civilians, it is 
not known if other culture-speciﬁ  c symptoms not part of the 
DSM-IV criteria that may have greater clinical relevance and mean-
ing to a speciﬁ  c refugee group. A general principle demonstrated by 
the World Health Organization cross-cultural study of depres-
sion,(36) i.e. that while some depressive symptoms may be present 
across cultures, they may not be the symptoms most strongly 
endorsed by the patient; this principle may also apply to PTSD. 
Figure 7.10.1.2 provides an illustration, which can help to address 
the problem of psychiatric diagnoses in refugee patients. This ﬁ  gure 
suggests that, until further research is forthcoming, the psychiatric 
provider needs to determine clinically whether the refugee patient 
is presenting with scenario A, B, or C.
The high prevalence of psychiatric symptoms associated with 
trauma in refugee populations neither afﬁ  rms nor negates the

trauma in refugee populations neither afﬁ  rms nor negates the 
‘normalization’ of these symptoms. A narrow medical viewpoint 
could create a psychiatric redeﬁ  nition of refugee mental health 
problems that would place the majority of refugees in a ‘mentally 
ill’ box without any access to individual psychiatric care; on the 
other hand, the hostility of many humanitarian aid workers toward 
psychiatry has denied the seriously mentally ill refugee legitimate 
access to psychiatric treatment. There will probably be a compro-
mise at the intersection of public health objectives and the protec-
tion goals of humanitarian aid workers. In future, the presence of 
chronic and severe disability in refugee survivors will be the gold 
standard which drives the psychiatric and humanitarian rehabilita-
tion of refugee survivors.(37, 38)
Psychiatric screening

If mental health practitioners are to treat refugee patients, they 
must be able to assess the refugee’s major risk factors and traumatic 
outcomes. Simple screening instruments culturally adapted to the 
language, trauma, and symptoms of refugee patients have been 
found to be extremely effective as well as being well received by 
refugees themselves.(39–41) For example, a simple well-known 
Fig. 7.10.1.2 Comparison of diagnostic classiﬁ  cations.

1497
screening instrument adapted from the Hopkins Symptom 
Checklist allowed Indochinese patients for the ﬁ  rst time to provide 
their symptoms with little distress. The development of the Harvard Trauma Questionnaire further revealed that these same patients could provide answers to lists of possible trauma events and symp-toms without becoming retraumatized. Overall, two major lessons have been learned from the use of simple checklists with refugee survivors.
1 The checklist acknowledges the traumatic life experiences of the 
refugee survivors and de facto  gives them permission to elaborate 
on the details of their trauma.
2 The checklist, as a simple medical test, helps refugees to ‘put 
words around’ events and symptoms that would be too emotion-ally overwhelming for them in an open-ended interview.
Extensive research regarding appropriate methods of develop-

ment, translation, and validation of the clinical screening instru-ments such as the Hopkins Symptom Checklist and Harvard Trauma Questionnaire has been widely disseminated.
(29, 42)
Understanding somatic complaints
For years it was considered standard psychiatric wisdom that emo-tional distress, especially in non-Western patients, was primarily somatic in character; and that, because of their dominant expres-sion of suffering through somatization, these patients were not psychologically minded, making them incapable of participating in psychotherapy or counselling. Extensive clinical experience and scientiﬁ  c studies with refugee patients throughout the world have

led to a revision of these previously dominant professional atti-tudes. While it may be valid that some refugees primarily present their emotional suffering through somatic complaints, it has also been found that it is fairly easy for the medical practitioner to obtain from refugee patients deeper insights into their feelings and their beliefs as to the causes of their emotional distress. Often because of severe victimization, refugees as a group will not readily 
share their experiences of trauma and related medical and psychi-
atric injuries unless they are in a highly conﬁ  dential environment 
where it is clear that the medical team can be trusted. In fact, the ability of refugee patients to extend themselves beyond their initial somatic complaints, as well as participating in clinical dialogue with the psychiatric practitioner as to the nature of their mental distress, is more the rule than the exception and is a major goal of assessment.
(43)

(43)
The trauma story
The trauma story emerges as the centrepiece of any treatment approach. Every refugee patient has at least one traumatic experi-ence that ﬁ  gures prominently in his or her life history. The trauma 
story is a living reality and is present for every patient. The trauma story is also present for the clinician. Y et, the story can be elusive and difﬁ  cult for both patient and doctor to share. Often times when 
the patient is ready to tell the trauma story, the clinician is not ready to hear it. More frequently, when the clinician is ready for the patient to tell his or her story, the patient is unwilling. Therefore, one of the major goals of psychotherapy with refugees is to allow the trauma story to emerge gently and become a familiar and acceptable theme, which the refugee is not shamefully hiding from his or her therapist and ultimately his or her family and 
(44)

(44)
Although commonly conducted within populations who have 
experienced trauma, typically by relief workers or crisis counsel-lors, debrieﬁ  ng has been shown to have negative effects on psychi-
atric outcomes and should be avoided at all costs.
(45) As described 
above, the trauma story should be allowed to emerge naturally and at the patient’s own pace.
Psychiatric treatment of refugee patients should primarily be based upon standard psychiatric practices for mentally ill patients, includ-ing the appropriate use of psychotropic medicines. However, a number of novel therapeutic approaches have been used with refugees. Recent research in refugee populations has indicated that cognitive behavioural therapy (CBT) is efﬁ  cacious for treatment-
resistant PTSD and panic attacks
(46, 47) and in refugees who have 
experienced torture.(48) Interpersonal psychotherapy for depres-
sion has been found to be useful in rural Uganda.(49) This approach

sion has been found to be useful in rural Uganda.(49) This approach 
may also be effective with resettled refugees in Western countries. In female veterans of war, prolonged exposure therapy was more effective over time than other interventions for reducing symptoms of PTSD in female veterans of war. It may be possible and beneﬁ  -
cial to use prolonged exposure therapy for others with PTSD.
(50)
Similarly, although no research has speciﬁ  cally examined the effects

(50)
Similarly, although no research has speciﬁ  cally examined the effects 
of therapies such as eye movement desensitization and reprocessing (EMDR) for refugees, positive results have been seen in a variety of different studies done with traumatized populations, including individuals with PTSD. Traditional medicine, which includes diverse health practices, knowledge, and beliefs is widely accepted and practiced worldwide. Traditional medicine typically relies upon local classiﬁ  cations of emotional distress and its treatment 
can incorporate plant-, animal- or mineral-based medicines, as well as spiritual therapies or massage.
(45) Traditional healing 
approaches were widely used for the Cambodian refugee crisis of the 1990s.
(51–53)  Although widely used, no conclusive research has 
yet been done using complementary treatments such as massage, acupuncture or herbal medicine in the treatment of torture survivors.

(14) Recent research with Cambodian refugees it was 
shown that interventions supporting work, altruism, and spiritual-ity for refugees might serve as protective factor for the onset of psychiatric disability.
(54)
Special considerations
A number of special considerations have emerged from the many therapeutic approaches that have been tried with refugees.
Family focus
Treatment should be directed at the entire family of the identiﬁ  ed

Treatment should be directed at the entire family of the identiﬁ  ed 
refugee patient. The refugee crisis tends to initiate a process in which surviving family members become each other’s major social support system. The disruption and disintegration of stable commu-nities and traditional social supports place the entire burden of survival upon family members. Sometimes in extreme situations that affect the family unit such as when a refugee is experiencing symptoms of depression, psychosis, or social withdrawal, the psy-chiatrist must reach out to the patient and establish a one-to-one therapeutic relationship until family members can be of assistance.7.10.1  the special psychiatric problems of refugees

SECTION 7  social psychiatry and service provision 1498
Cultural sensitivity
The cultural sensitivity of refugee mental health practitioners is 
essential to the proper therapeutic relationship to the refugee patient. This means that the refugee mental health practitioner must be informed as to the type of trauma experienced by the refugee and its socio-cultural meaning, the cultural idioms by which human suffering is expressed in a given community, and the social stigma associated with mental illness. Despite the refugees’ own adversity, long-standing social prejudices against mental ill-ness will persist throughout the refugee crisis.
Little cross-cultural literature exists on the relationship between 
refugee patient, Western professional, and bilingual interpreter. 
The use of refugees as interpreters can be problematic. Ideally,

The use of refugees as interpreters can be problematic. Ideally, 
health professionals from the refugee communities should be recruited to participate in psychiatric intervention. These individu-als have had professional medical training as to the importance of conﬁ dentiality and can also provide insight into the cultural nuances

of the doctor–patient relationship. The use of untrained interpret-ers from the refugee community should be avoided if at all possible. This is especially true of family members or members of a com-munity or government institution that has previously threatened the security of the refugees. In addition, medical practitioners must respect patient dignity by not allowing young people to interview community elders or males from the community to ask refugee women explicit sexual questions and/or witness or be exposed to an undressed refugee woman during a medical examination. The more the bicultural interpreter can function in the role of a trained mental health paraprofessional, the more successful will be the therapeutic experience of all involved.
Caring for the seriously mentally ill

Despite numerous biases against psychiatric intervention in refugee populations, psychiatrists are well positioned to treat the seriously mentally ill refugee. In most refugee camps, those in immediate danger are the psychotic and depressed refugees with suicidal ide-ation. These individuals have difﬁ  culty coping with their ongoing 
crisis and have high mortality rates. Once resettled, these refugees with serious mental health issues need appropriate medical and mental health services.
(55)
Special treatment needs of gender-based violence
Many colleagues in the ﬁ  eld of refugee mental health have sought 
to break the ‘conspiracy of silence related to sexual violence’ .(32)
While this issue has been well documented in refugee communi-ties, it was not until the Bosnian conﬂ  ict that rape was ﬁ  nally

While this issue has been well documented in refugee communi-ties, it was not until the Bosnian conﬂ  ict that rape was ﬁ  nally 
accepted by the international community not as a criminal act but as a crime against humanity. This recognition of gender-based vio-lence as the most common type of torture of women, as well as a major terrorist instrument of war, has contributed to the protec-tion and psychiatric care of sexually abused refugee survivors. While the political will now exists to condemn rape, and to protect refugees from it, the cultural stigma and corresponding social pun-ishments of women considered ‘tainted’ by sexual violence, some-times including their murder (‘honour killing’) by relatives, continues to make the psychiatric care of these survivors extremely difﬁ cult. In most cultures, rape remains a secret issue caused by the 
refugee’s extreme resistance to reveal any details to the physician.

refugee’s extreme resistance to reveal any details to the physician. 
Psychiatric practitioners must approach this issue with extreme caution in a strictly conﬁ  dential manner. They must also be aware of the severe consequences to the patient if the rape experience 
becomes public knowledge, even to the patient’s family members.
Risk and resiliency factors
The pre- and post-conﬂ  ict personality characteristics of refugees 
that increase resiliency and reduce psychiatric distress and disability are not known. While certain demographic characteristics have been associated with negative traumatic outcomes, these character-istics may be confounded by other risk factors. Women, especially widows, seem especially vulnerable to negative refugee effects. UNICEF has extensively reviewed those risk factors associated with the vulnerability of refugee children and adolescents.
(56) Data from

(56) Data from 
Bosnian refugees correspondingly reveal the high rates of disability associated with trauma and psychiatric comorbidity in the elderly.
Lessons learned from studies of political prisoners in Turkey 
reveal the importance of a well-established political world view as a major protection against the long-term human suffering associated with torture.
(57) Studies of Bhutanese refugees in Nepal conﬁ  rm 
the possible protective function of Buddhism in devout refugee practitioners of this religion.
(23) Anecdotal reports by refugees 
themselves consistently conﬁ  rm the emotional safety that they have 
found in their spiritual and religious beliefs and practices. Finally, recent research ﬁ  ndings concur with the earlier research in concen-

tration camp survivors and prisoners of war that prior psychiatric history and premorbid personality factors may have little effect on the psychiatric sequelae of traumatic refugee experiences. In reset-tlement countries, opportunities related to family uniﬁ  cation, 
learning to speak the new country’s language, and employment have clearly been shown to be associated with decreased psychiatric morbidity over time. Those who provide psychiatric care for refugees must keep in mind the environmental opportunities that can increase their overall resiliency.
Reducing risk and maximizing resiliency

Figure 7.10.1.1 provides a readily accessible model for psychiatric practitioners to determine how they can reduce the risk factors associated with psychiatric disorders as well as promote the resil-iency of the refugee patient. The section on risk factors provides many useful insights into the importance of enhancing the refu-gee’s active role in work, spiritual participation, involvement in altruistic behaviour, and the many other personality and environ-mental factors that can directly reduce depression and other forms of psychiatric distress.
www.hprt-cambridge.org <http://www.hprt-cambridge.org> (Harvard 
Programme in Refugee Trauma)
http://mentalhealth.samhsa.gov/cmhs/SpecialPopulations/refugmhnew.
asp (U.S. Substance Abuse and Mental Health Services Administration, Refugee Mental Health Division)
www.unhcr.org (United Nations High Commission on Refugees)

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7.10.2 Mental health services for 
homeless mentally ill people
Deﬁ nition and demography of homelessness 
and its link to mental illness
The term ‘homeless’ has been used to describe populations as

The term ‘homeless’ has been used to describe populations as 
diverse as those sleeping in the shelter of a cardboard box, to those sleeping on a friend’s ﬂ  oor. Given such wide deﬁ  nition, it is not 
surprising that estimates of the numbers involved vary greatly from survey to survey and from one country to another. But regardless of the deﬁ  nition, there is consensus that the numbers of homeless 
people in most Western urban areas increased during the past two decades, reﬂ  ecting a scarcity of low-cost housing, the erosion of 
traditional family networks, and downsizing in the organization and delivery of supportive services. Of all these factors, the

traditional family networks, and downsizing in the organization and delivery of supportive services. Of all these factors, the 
shortage of affordable accommodation is the most important. For example, in England there has been a 40 per cent increase since 2002 in the number of households on waiting lists for social hous-ing with estimates that a minimum of 20 000 housing units above current government targets are required to simply meet newly arising urgent need.
(1)
Compared with a domiciled population, homeless people are less 
likely to have completed basic education, less likely to have ever held employment, and more likely to have experienced parental neglect and abuse in their childhood.
(2)
Given the evidence linking homelessness to poverty and social

(2)
Given the evidence linking homelessness to poverty and social 
disadvantage, it is hardly surprising that homeless people report higher rates of psychiatric disorder relative to the general popula-tion. While rates vary depending on the particular measure of mental illness adopted by each study and by the homeless popula-tion being investigated, most report major psychiatric disorder in 30 to 60 per cent of those using emergency shelters and sleeping rough. The prevalence of schizophrenia and other psychoses is particularly high amongst the middle-aged residents of long-stay hostels, while depression, generalized anxiety, and impulsive self-harm are more typically encountered in younger runaways and adolescent populations. Alcoholism and drug dependency are pres-ent in as many as two-thirds of men and a third of homeless women. Co-morbidity of mental illness and substance use disorder 
is the rule rather than the exception as are the co-occurrence

is the rule rather than the exception as are the co-occurrence 
of respiratory disease, infections, trauma, and the physical consequences of poor diet, poor hygiene, and the complications of substance abuse. Of growing concern is the accumulation of older multiply disabled populations in some North American cities.
(3)
The typical pattern of service utilization of the severely mentally 
ill among the homeless population is one of extremes—bursts of involuntary hospital admissions and compulsory treatment inter-spersed with long periods of neglect and isolation. Many of those who are found sleeping rough or resident in temporary shelters have found their way to these locations as a conscious effort to avoid contact with health and social care professionals and remain unwilling to be part of any structured rehabilitation programme.
Barriers to care
Poverty and isolation

Very few homeless mentally ill people have satisfactory links to family or other supportive social groups. Unemployment is the norm and many have histories of contact with the criminal justice system. The lack of supportive kinship networks mean that there is 
seldom anyone who has an interest in their welfare and no one on 
whom services can rely for informal care giving. Affordable hous-ing is likely to be of poor quality and unsupervised. Landlords are reluctant to rent property to someone with a history of destructive behaviour, a criminal record, or manifest mental illness.
Barriers arising from the illness

Severe mental illness contributes to incompetence in many aspects of daily life, with impaired social function and problems initiating and executing daily living tasks that require a degree of forward planning. Co-morbid cognitive impairment or substance abuse compound these problems. Many homeless patients will have lost their accommodation as a direct result of their illness, being evicted

1501
for failing to keep up with rent payments, neglecting or damaging 
the property, or following complaints from neighbours.
Barriers put up by services
The lack of common purpose and co-ordination of social welfare, health, and criminal justice agencies lies at the heart of many difﬁ  -
culties faced by homeless mentally ill people. A young homeless person, for example, may be too chaotic to undertake the retrain-ing programme that is his only route to welfare support, may be unable to register with a local family health centre because of his lack of a permanent address, and may be summarily rehoused without reference to health services involved in his care. Finally, the prejudices of professionals can make services unacceptable and the emphasis on treatment is seldom attractive to a homeless person whose immediate needs are for food, shelter, and security.
Principles of service organization 
and delivery
T o state the obvious, the solution to problems of homelessness

T o state the obvious, the solution to problems of homelessness 
lies in the provision of suitable accommodation, targeted efforts to re-house the most vulnerable, and sufﬁ  cient longer-term tenancy 
support to prevent a return to the streets. While many countries have social welfare legislation to assist homeless people, only a 
minority provide a legally enforceable right to suitable accommoda-
tion for vulnerable populations. The Rough Sleepers Initiative in 
England, provides emergency accommodation for the roofless 
population and follows this emergency re-housing with a T enancy 
Sustainment Programme of ﬂ  exible practical and emotional sup-
port to prevent future accommodation breakdown.
(4) This has been 
very successful in reducing the numbers of rough sleepers though gaps remain, particularly for people suffering from severe mental illness and s ubstance dependency. For these populations, a further

very successful in reducing the numbers of rough sleepers though gaps remain, particularly for people suffering from severe mental illness and s ubstance dependency. For these populations, a further 
tier of service involving specialized mental health provision is needed either as part of an intensive initial stabilization
(5) or in the 
longer-term. While the detail of specialized services varies according to local circumstances, they are all based on a small number of ideo-logical and organizational principles (Table 7.10.2.1).
Improved inter-agency co-operation
As a ﬁ  rst step, most involve a steering group comprising senior 
representatives of the key stakeholders in health, housing, social services, police, and voluntary sectors. These groups oversee the 
development of services across a wide geographical area—a large sector of a city or state. The members carry sufﬁ  cient political and

development of services across a wide geographical area—a large sector of a city or state. The members carry sufﬁ  cient political and 
managerial authority to be effective in dealing with bureaucratic obstacles that are bound to arise from time to time.
Providing local multidisciplinary specialist teams
This co-ordination is replicated at the local level through multi-disciplinary clinical teams, joint working, and case management. Such partnership ventures have been established in several cities in North America, Europe, and Australia using a variety of organi-zational approaches ranging from a single multidisciplinary team through ‘one-stop shops’ where professionals from a variety of backgrounds come together to provide services at a common location.
Essential components of the specialist service

The management of a homeless mentally ill person involves stages of engagement, stabilization, resettlement, and the eventual transfer of care to mainstream providers. Engagement can take a long time, staff must be prepared to leave the clinic and go to where homeless people congregate. Help with welfare and practical problems may be all that can be done at ﬁ  rst but the duty to maintain a thera-
peutic focus must always be maintained. Stabilization requires the specia list assessment and treatments provided to any mentally ill person, including hospital admission if necessary. The task of resettlement typically involves a compromise between personal preferences, available resources, and the level of support needed to promote rehabilitation. For example, independent accommodation may be a person’s ﬁ  rst choice but may only be a viable prospect 
if it can be backed up by weekly visits from the mental health

if it can be backed up by weekly visits from the mental health 
team. Core and cluster arrangements, in which residents have their own ﬂ  at but receive supervision from an on-site warden with-
in the complex is a particularly effective model for those who have failed in independent accommodation but who reject shared facilities.
The eventual transfer of care to mainstream services can be quite 
difﬁ cult to manage and most follow-up studies suggest that fewer 
than half of those transferred remain in treatment.
Specialist multidisciplinary teams for homeless mentally ill people provide an essential safety net for those who have fallen out of the wider mental health care system. They offer distinct advantages in terms of their capacity to work across traditional geographical and bureaucratic barriers, to take the longer-term view of the task of 
engagement, and to bring together the multiple strands of care 
across different provider agencies. Introduced as a temporary

across different provider agencies. Introduced as a temporary 
measure over a decade ago, they are still with us and likely to remain 
a permanent ﬁ  xture of urban mental health care.
Access to mental health services for people who are homeless or living in 
temporary or insecure accommodation. A good practice guide: http://www.communities.gov.uk/index.asp?id=1162512
Essential statistics on homelessness in Britain: http:// www.homeless.org.
uk/policyandinfo/facts/statisticsTable 7.10.2.1  Services for homeless mentally ill people
Essential components for rehousing
  Availability of temporary accommodation with a pathway to permanent 
housing
 Capacity to deliver basic needs (shelter, food, income support) Ongoing practical support to maintain tenancy
Specialized mental health service

housing
 Steered by a partnership of key stakeholders (housing, health, welfare, etc.) Multidisciplinary front-line team Assertive outreach model Capable of managing mental illness and substance-use disorder
Wider context
 Community-orientated mainstream psychiatric services  Inﬂ  uence of central and local government policies on health, welfare, and 
criminal justice7.10.2  mental health services for homeless mentally ill people

SECTION 7  social psychiatry and service provision 1502
 1. National Housing Federation. (2006). England’s housing time-bomb: 
affordability and supply 2006–11 . National Housing Federation, 
London. Website: http://www.housing.org.uk/uploads/ﬁ  le/campaigns/
tb_england.pdf
 2. Bhugra, D. (ed.) (1996). Homelessness and mental health .
 3. Hahn, J.A., Kushel, M.B., Bangsberg, D.R., et al. (2006). The aging 
of the homeless population: fourteen-year trends in San Francisco. 
Journal of General Internal Medicine ,21, 775–8.
 4. Lomax, D. and Netto, G. (2007). Evaluation of tenancy sustainment 
teams. Department of communities and local government.http://www.odpm.gov.uk/index.asp?d=1505917
 5. Susser, E., Valencia, E., Conover, S., et al. (1997). Preventing recurrent 
homelessness among mentally ill men: a ‘critical time’ intervention after discharge from a shelter. American Journal of Public Health ,
87, 256–62.

7.10.3 Mental health services 
for ethnic minorities
Ethnicity, culture, and health care need
Services aimed at minority ethnic populations are all too often 
developed on the basis of conspicuous morbidity than on any real understanding of the diversity of ethnic minority communities and their wider health needs. For example, in England, while much has been written about ethnicity and psychiatric morbidity, the literature remains largely focused on African-Caribbeans and Asians, while the needs of the Irish, who comprise the largest ethnic community by migration in many parts of the UK are seldom explicitly addressed despite evidence of high rates of suicide and unexplained death many times in excess of the indigenous population.
(1) In

(1) In 
addition, the large numbers of asylum seekers and refugees who move around the world, brings an increased need for culturally sensitive services. But very few models exist for developing these. The principles of good practice indicate that the start has to be a clear knowledge of the population that will be accessing services and an appreciation of the complicating factors of social disadvantage, material deprivation, and poverty.
There is no doubt that social disadvantage and racial prejudice 
whether real or perceived are pivotal in determining not only the mental health of minority populations but also the pathways indi-viduals and their families use in seeking help for ill health. Delays in help-seeking can also be due to the stigma of mental illness and to sufferers’ fears that they will be misunderstood and mistreated 
because of differences in culture, language, and racist attitudes

because of differences in culture, language, and racist attitudes 
within the services. These factors may be more apparent in older individuals and those who were born outside the country who may not be aware of various options available to them. Studies over the past 30 years or more in Britain, the Netherlands, the United States, Canada, and Australia have shown that minority groups have lower access to mental health services, are less likely to receive care, and when they do this is more likely to be of a lower quality. Black people in the UK and the United States are more likely than white 
people to be compulsorily detained in hospital, to be screened for drug abuse, to receive higher doses of medication and physical rather than psychological therapies. They are over-represented compared with their numbers in the general population, whether in general wards, locked wards, secure units, court diversion schemes, special hospitals, or prisons.
(2)

(2)
Some of these problems can be attributed to a lack of under-
standing on the part of mental health practitioners of the cultural beliefs, values, and practices of minority groups with consequent shortcomings in assessment, diagnosis, and the provision of care. While language can be a major obstacle, for many people from minority ethnic groups who speak English the problem is of com-munication rather than language. The power dynamic that is always present in any clinical consultation is magniﬁ  ed and both patient 
and doctor will have predetermined expectations of how their inter-action will turn out depending upon their experience of previous consultations. Problems in the interaction are likely to be interpreted as arrogance and racism on the one hand and indifference, wariness, or docility on the other. Thus, both missed diagnoses and misdiagnosis may result. A lack of recognition of the personal, social, and cultural problems which influence the presenting

patterns of symptoms in different ethnic groups can contribute to 
the tendency of clinicians to make assumptions and listen out for stereotypical triggers which then prompt a particular therapeutic response. Such triggers include religious euphoria, use of Cannabis in African-Caribbeans, and the ‘fatalistic attitude’ attributed to Asian patients.
Culturally competent services
The past decade has seen an emerging consensus that the way forward lies in the development of fully integrated multicultural services with good working links with the local minority commu-nity rather than separate services. Such services would provide staff who can understand their client’s cultural background and the ways in which this inﬂ  uences the presentation of distress and

disorder. There would be closer working links with religious lead-ers and healers of local ethnic minority communities, female-only areas on wards, and a greater involvement and support of the fam-ily in understanding the problems and developing solutions.
In North America,
(3, 4) Britain,(5) and Australia(6) there has 
been a signiﬁ  cant ‘top–down’ pressure to shift health care organiza-
tions in this direction and several large-scale programmes such as the European 9-country ‘Migrant-Friendly Hospitals’ initiative
(7)
have been reported. Although differing in detail, all these pro-grammes share common elements. These principles are outlined in Table 7.10.3.1 setting out the main conclusions in a ‘bottom–up’ approach in order to emphasize the importance of changes in the attitudes, knowledge, and skills of front-line managerial and clinical staff.
Commonly referred to as ‘cultural competence’ these attributes

Commonly referred to as ‘cultural competence’ these attributes 
include attention to obvious language differences but go further to include history, traditions, beliefs, and values even if 
the latter differ from those held by the professional. A culturally 
competent clinician is sensitive to a patient’s cultural inﬂ  uences, 
expressions of distress and help-seeking, and is also aware of their own attitudes and prejudices and how these are in turn shaped by their own cultural background. This objective is achieved through

1503
training and a plethora of different cultural competency/diversity 
courses have sprung up in recent years. A search of the Internet identiﬁ  es courses in undergraduate nursing, medical, and pharmacy 
programmes, in post-graduate continuing professional develop-ment and as part of wider organizational change and development. While the moral argument for improved cultural competence is hardly contestable, whether or not these training courses are sufﬁ  -
cient to effect lasting change in behaviour and the delivery of health care is less certain. The very limited empirical evidence base is predominantly from the Unit ed States and shows efﬁ  cacy in terms 
of short-term changes in attitudes and knowledge. Evidence is still lacking on which elements of this training are essential and on the downstream effects on service quality that is the real target.
Table 7.10.3.1 also shows the other key steps that have been taken

Table 7.10.3.1 also shows the other key steps that have been taken 
towards developing more culturally sensitive services. Most health 
service providers have gone some way to providing female-only inpatient wards, more community-orientated service settings and addressing the need for expanding the numbers of people from minority backgrounds in their workforce though it is still all too easy to think that problems with cultural sensitivity can be solved with this alone. Simply hiring people on the basis of nationality, ethnicity, or skin colour will not necessarily ameliorate problems in the service. Typically these staff are the lowest in the hierarchy of 
power and have the least capacity for inﬂ  uencing either the care of 
the patient or wider attitudes within the institution. Even when employed in a position of power there is a danger of their appoint-ment being seen as tokenistic.
Another important step involves the elaboration of performance

Another important step involves the elaboration of performance 
indicators to assess the impact of training and service changes and ethnic monitoring with a focus on key areas such as the use of coer-cive treatments, treatment discontinuation, and ethnic differences in the uptake of psychological and pharmacological treatments. In the most sophisticated systems this includes both quantitative epidemiological and economic data as well as qualitative inputs from consultation with users, carers, and the general public includingcommunity and religious leaders.
(8)
Finally, at the wider community level, NGOs have often become

(8)
Finally, at the wider community level, NGOs have often become 
the champion of good practice, seen by their users as an antidote to inadequate mainstream care. These small organizations are gener-ally based on consultation with users, carers, and local mental health professionals and are more in tune with the expressed needs of the community. The best have good working relations with mainstream services, and are generally seen as making an impor-tant contribution to wider community care. They provide a range of supportive services and are ideal vehicles for health promotion and dissemination of health-related information. Given the need to develop ways of working which promote inclusion of patients, their families, and the community in general, it is impossible to overstate the importance of effective liaison between the voluntary sector and mainstream psychiatric services. People often come into contact with the emergency services because there is a lack of

knowledge of the availability of community alternatives and of 
where to go when distressed. Working with voluntary services will not only contribute to their longevity but also ensure that the com-plementary treatment modalities they offer are part of the service provided.
Even where these system-wide initiatives are absent or not yet 
fully implemented, individual clinicians can do a lot to improve the care of minorities within their own service. Finding out the scale of the problem is a good place to start. Are population estimates available from a recent census, is information available from a recent census or from local government sources? More important-ly, are there known problems of access for these populations in general or particularly within local mental health services? Are signiﬁ  cant numbers not treated because they are held in ‘inappro-

priate’ settings in the criminal justice system or because they are mobile populations? In terms of delivering the service, outreach is likely to be the key and this will almost always involve partnership arrangements, developing understanding of key cultural inﬂ  uences 
including the importance of alternative health perspectives, spiritu-
ality and traditional healing. Seve ral innovative services have been 
developed alongside organizations that ‘hold’ signiﬁ  cant numbers 
of the minority population such as the Church or the local Mosque or NGOs dealing with speciﬁ  c communities, which can provide a

of the minority population such as the Church or the local Mosque or NGOs dealing with speciﬁ  c communities, which can provide a 
wider social or housing service to minority populations. It is the near universal experience of these services that initial progress is slow with many barriers of mutual misunderstanding and suspi-cion to overcome. Developing a relationship or even employing someone from the minority culture as a go-between, advisor, or ‘cultural consultant’ can be helpful though it needs careful prepara-tion to avoid selecting a consultant from the wrong tribal Table 7.10.3.1  Organizational steps towards a culturally competent 
mental health service
1 Workforce level
Training in ‘cultural competence’ should be mandatory for all mental health 
professionals
 (a) Undergraduate programmes
 (b) Post-graduate as continuing professional development
2 Health care provider level

Provide accommodation, washing, and living space facilities that take into 
account different cultural and gender deﬁ  nitions of ordinary social behaviour, dignity, and respect.
Senior management responsibility and accountability for:
 (a) Active race equality policies
 (b)  Recruitment policy—to increase presence of minority staff and 
provision of training and support as needed
 (c) Ensure staff have received relevant cultural competency training
Ensure adequate data collection includes a robust estimate of the numbers of 
ethnic minorities using services with a focus on key areas such as disparities by ethnicity in the use of coercive treatments, dropout from follow-up; 
differences in the uptake of psychological and pharmacological treatments.
Specialized outreach services targeting mentally ill people in the criminal

Specialized outreach services targeting mentally ill people in the criminal 
justice system, homeless, and refugee populations.
Partnership arrangements with NGOs including the provision of volunteer 
advisors and of translation services that do not rely on relatives or other 
informal carers.
3 Wider health service level
At the appropriate Regional or National HMO or Statutory Organization: (a)  Policy and practice commitment to removing barriers to access, e.g. 
extend health insurance to the uninsured and closer integration of primary and secondary mental health care
 (b)  Collection of good quality demographic information and ethnic 
monitoring for planning and overseeing services
 (c)  Minority representation at all levels of health service planning and 
delivery
Continue to expand the science base to determine what works best for whom7.10.3  mental health services for ethnic minorities

SECTION 7  social psychiatry and service provision 1504
background or at the wrong level  of seniority, gender, or language 
group. Culture broker models have been used in the United States, whereas cultural consultation services happen in parts of the UK and cultural liaison ofﬁ  cers are used in parts of Australia. 
Whatever the choice, it is likely to take time and patience to develop a high level of ‘visibility’ in the target community as well as a sound understanding of its culture, taboos, and historical context. Where available, cultural supervision from a more experienced practitioner is also helpful. The underlying principle has to be a two-way process, which deals with information from the patient’s community and the service provider to ensure that communica-tions are clear.
A few further points can usefully be taken into account in plan-

ning the service. First an understanding of local models of illness that determine when and how and of whom help will be sought, second use of local epidemiological data to assess the impact of age and gender on service demand and ﬁ  nally the involvement of the 
local community to promote a sense of ownership and involve-ment in the delivery of services.
In conclusion, the diagnosis and treatment of mental ill health 
among multiethnic populations is probably one of the most complex and contentious challenges in psychiatric service provision. At the heart of this complexity are problems of ignorance, attitude, and failures of communication on all sides. It is also potentially one of

the most rewarding endeavours if got right. No one service model is likely to apply to every community, even if people belong to the same ethnic group. The development of specialist psychiatric services may not always be possible or even essential. Instead, the 
requirements are for approaches that are ﬂ  exible, sensitive, accessible, 
and accountable to the people they serve.
American Psychological Association guidelines for providers of services to 
ethnic linguistic and culturally diverse populations: http://www.apa.org/pi/guide.htmlSainsbury Centre for Mental Health. (2002). Breaking the circles of fear 
http://www.scmh.org.uk
 1. Bhugra, D. (2004). Culture and self-harm . Psychology Press, Hove.
 2. Lipsedge, M. (1993). Mental health: access to care for black and ethnic 
minority people. In Access to health care for people from black and 
ethnic minorities  (eds. A. Hopkins and V . Bahl), pp. 169–83. 
Royal College of Physicians, London.

 3. Ofﬁ  ce of Minority Health (USA). Assuring cultural competence in 
health care: recommendations for national standards and an outcome-focused research agenda. www.omhrc.gov/Assets/pdf/checked/Assuring_Cultural_Competence_in_Health_Care-1999.pdf
 4. Mental Health: Culture Race and Ethnicity. A supplement to Mental 
Health: A Report of the Surgeon General. www.surgeongeneral.gov/library/mentalhealth/cre/
 5. Department of Health. (2005). Delivering race equality in 
mental health care: an action plan for reform inside and outside 
services and the government’s response to the independent 
inquiry into the death of David Bennett . HMSO, London. http://
www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_4100773

 6. Royal Australasian College of Physicians. (2005). Policy statement: 
aboriginal and T orres Strait Islander Health. Available at:http://www.racp.edu.au/index.cfm?objectId=49F4E2A9-2A57-5487-
D0597D1ED8218B61
 7. Migrant-Friendly Hospitals Initiative. (2004). Available at: 
http://www.mfh-eu.net/public/home.htm
 8. Jordan, J., Dowswell, T., Harrison, S., et al. (1998). Health needs 
assessment. Whose priorities? Listening to users and the public. British 
Medical Journal ,316, 1668–70.

8.1 The biology of ageing  1507
1524
1530
Claudia Jacova and Howard H. Feldman
 8.5.2 Substance use disorders in older people  1540
Barton W. Palmer, Gauri N. Savla, and Thomas W. Meeks 8.5.4 Mood disorders in the elderly  1550
 8.5.5 Stress-related, anxiety, and obsessional disorders in elderly people  
1558
1564

1558
1564
1579
Pamela S. MeldingSECTION 8
The Psychiatry 
of Old Age

8.1
Although old age is readily recognizable, methods to deﬁ  ne and 
measure the underlying biological processes are much less amena-ble to study. For this reason, life expectancy  has been widely used 
as a surrogate measure of ageing, as well as to monitor economic progress at national and regional levels. It is generally acknowl-edged that lifespan is a constitutional feature of the human pheno-type, and twin studies have indicated that 25–33 per cent of the variance in human longevity  is genetic in origin.
(1,2) External 
factors including lifestyle can also exert a major inﬂ  uence, as illus-
trated by the current mean life expectancies of 79 and 86 years for males and females in Japan, whereas the comparable ﬁ  gures for 
Botswana are 35 and 33 years, respectively.
The importance of genetic inheritance as a determinant of

The importance of genetic inheritance as a determinant of 
extended survival has been illustrated by population level studies in Okinawa, an island prefecture of southern Japan with a very high prevalence of long-lived individuals. On the island, the mortality rates of the male and female siblings of centenarians were approxi-mately half those of birth cohort-matched, non-centenarian siblings.
(3) These ﬁ  ndings parallel an earlier study of the family of 
Jeanne Calment, who died in France in 1997 aged 122 years. Of her 55 relatives, 24 per cent had lived to >80 years compared to just 2 per cent of a matched control group.
(4) However, it remains 
unclear whether the enhanced lifespan of individuals who exhibit above average longevity is due to a slowing of the overall ageing process or is primarily associated with resistance to major life-threatening pathologies.
The concept of an ‘ allostatic load ’ , potentially involving the

The concept of an ‘ allostatic load ’ , potentially involving the 
neuroendocrine, sympathetic nervous, immune and cardiovascular systems, and metabolic pathways, has been advanced to describe the lifetime costs of adapting to physical and psychological stresses. According to this hypothesis, while the actions of biological mediators of stress  can be initially beneﬁ  cial to health, chronic 
stimulation results in regulatory imbalance and subsequent pathophysiological changes.
(5) Empirical studies have indicated 
increased physiological dysregulation and functional decline at >70 years of age, which would imply that predicted global increases in the numbers of older persons will be accompanied by dispro-portionately larger groups of individuals with major age-related pathologies.Theories of ageing

While initially popular, it became apparent that single, ‘magic bullet’ causes of ageing were inappropriate to complex biological species, and with this recognition earlier organ- and system-based theories have gradually been discounted. Conversely, the observa-tion that ageing appears to be initiated at different ages and can proceed at different rates in individual members of a species provides presumptive evidence for the interaction of multiple genetic and non-genetic inﬂ  uences. Two main groups of theories 
have been formulated, genomic and stochastic, each subdivided into a number of discrete topic headings.
Genomic theories of ageing
Genomic theories  premise that ageing is primarily associated with

Genomic theories  premise that ageing is primarily associated with 
changes in the genetic constitution of the organism. Support for genomic theories stems largely from the characteristic life expect-ancies of mammalian and non-mammalian species, and theories proposing a primarily genetic basis for ageing were greatly strength-ened by the demonstration that human diploid cells exhibited a highly reproducible lifespan when cultured in the laboratory. Although strong evolutionary advantages can be envisaged for genetic control of developmental changes up to and including reproductive adulthood, the existence of genes uniquely encoding ageing seems improbable since few free-living animals or humans have ever succeeded in attaining the maximum lifespan of their species.
(a) Information transfer

The ability to synthesize functional proteins is dependent on the ﬁ delity of genetic information encoded in the DNA, its unimpaired 
transcription from DNA to RNA, and translation into peptides and proteins. As each of these processes is subject to inaccuracy, and during the life course of an organism the sequence of information transfer steps is continuously operational, the error potential is large. With increasing chronological age the probability of errors increases, resulting in the accumulation of deleterious mutations late in life.
(6) Since a number of the proteins synthesized may be 
involved as surveillance enzymes to maintain the accuracy of the entire system, feedback mechanisms could lead to its collapse, resulting in a phenomenon initially termed error catastrophe .The biology of ageing

1508
(b) Somatic mutation
With the demonstration of an inverse correlation between the 
lifespan of mammalian species and the incidence of chromosome abnormalities, age-related physiological changes were originally ascribed to accumulated mutations in the nuclear DNA ( nDNA ) of 
somatic cells. Findings of this nature could, however, be explicable in terms of the ability of an organism to tolerate DNA damage via the repair of damaged molecules, with more than 130 human DNA 
repair genes  identiﬁ  ed.
(7) The capacity of nDNA to resist attack by 
endogenous reactive species and environmental agents is therefore considerable, which casts doubt on the general applicability of the theory.
(c) Epigenetic mechanisms
Epigenetic errors, i.e. errors in the control of gene expression rather than mutations in DNA or protein, have been proposed as major primary causal factors in senescence.
(8) In promoter regions of

(8) In promoter regions of 
genes, hypermethylation silences a gene whereas the hypomethyla-tion of previously methylated sequences permits their expression. The pattern of DNA methylation  is established during develop-
ment and is cell type-speciﬁ  c, and changes in methylation can 
occur both during ageing and in cancer cells. The advantage of epigenetic models of ageing is their lack of requirement for the evolutionary preservation of genes encoding ageing, which in former generations would seldom have been expressed.
(d) Mitochondrial decline

Mitochondria are subcellular organelles responsible for aerobic energy production in humans and many other species. The mito-chondrial genome of ~16.5 kb is characterized by its extremely compact organization, with no protective histones, a lack of exci-sion or recombinational repair mechanisms, and a virtual absence of introns, all of which make it highly susceptible to mutation. Mitochondrial DNA ( mtDNA ) plays a central role in mitochon-
drial propagation and the maintenance of cellular respiration, but a majority of proteins involved in the regulation of mtDNA tran-scription, translation and replication, and the mitochondrial respiratory chain, are encoded in the nuclear genome. This design requires the operation of a highly coordinated mechanism for the expression of the nuclear and mitochondrial genomes. The central role of mitochondria in energy production means that defects may 
be of major metabolic signiﬁ  cance, and the demonstration of

be of major metabolic signiﬁ  cance, and the demonstration of 
increased levels of mtDNA deletions and base-substitutions in aged human neurones, heart, and skeletal muscle suggest a causative role for mtDNA mutations in ageing.
(9)
(e) Telomere loss
T elomeres are specialized structures located at the terminus of the DNA helix and critical to the maintenance of DNA stability and replication. The enzyme telomerase which is responsible for telomere synthesis is active during early embryonic and foetal development but its activity is down-regulated in all human somatic cells before birth. As human diploid ﬁ  broblasts in culture were 
shown to progressively lose telomeres, it was hypothesized that telomere length could act as a predictor of the potential in vitro
lifespan achievable by a cell strain.
(10) Humans have a common 
telomere proﬁ  le found on lymphocytes, amniocytes, and ﬁ  brob-

lasts which appears to be preserved throughout life. However, the rate of telomere loss with ageing varies between chromosomes and there is evidence that, in addition to the common human telomere proﬁ  le, each person exhibits an individual proﬁ  le.
(11)Besides ageing, telomere loss has been implicated in a wide range of 
disease states, including heart disease, stroke, infection, long-term chronic stress, and ob esity. Given the apparent relationship between 
telomere loss and both ageing and age-related pathologies, phar-macological activation of telomerase has been proposed as a poten-tial treatment for chronic or degenerative diseases.
(12) As tumour 
tissue and transformed cells constitutively produce telomerase, any therapeutic intervention of this nature would require careful monitoring.
Stochastic theories of ageing

Stochastic theories  of ageing propose that cumulative adverse 
random changes at the cellular level ultimately overwhelm the capacity of an organism to survive, with ageing representing the preceding period of functional decline.
(a) Rate of living
An optimum lifespan was achieved by a variety of non-mammalian species when the organisms were maintained at suboptimal temperatures. The further demonstration of an inverse relation-ship between basal metabolic rate and longevity in mammals was interpreted as evidence that a species lifespan was governed by its rate of living , which in turn was correlated with its level of energy 
expenditure. Theories of this type tend to be imprecise in deﬁ  ning

expenditure. Theories of this type tend to be imprecise in deﬁ  ning 
the nature of the factor(s) controlling ageing and lifespan, although it was subsequently proposed that the rate of living theory could be reformulated as a stress  theory of ageing, with stress resistance and 
longevity positively correlated.
(b) Waste product accumulation
Ageing has been ascribed to interference by accumulated waste products in normal cellular metabolism and function, ultimately resulting in dysfunction and death at cellular and organ levels. Lipofuscin, a highly insoluble, pigmented compound derived by auto-oxidation from incompletely degraded cellular materials and detected with advancing age in neurones, cardiac muscle ﬁ  bres, 
and the adrenal cortex, has been particularly implicated. Alternatively, the build-up of lipofuscin in older organisms may be secondary to an age-related decline in the function of cellular catabolic processes.
(c) Macromolecule cross-linkage

Many macromolecules of biological importance develop cross-links with increasing chronological age. The establishment of cross-linkage, whether covalent in nature or due to hydrogen bonding, alters the chemical and physical properties of molecules. Thus cross-linkage of the extracellular protein collagen is believed to be responsible for the loss of elasticity in mammalian blood vessels and skin with advancing age, even though collagen is sub-ject to turnover throughout the lifespan. DNA and RNA also are believed to be potential intracellular targets for cross-linking agents, and changes in their structure could have serious functional implications for cellular information ﬂ  ow.
(d) Post-synthetic modiﬁ  cation
In addition to cross-linkage, molecular aggregation and immobili-
zation that compromises cellular metabolism and function could be caused by post-synthetic modiﬁ  cation of proteins, with

zation that compromises cellular metabolism and function could be caused by post-synthetic modiﬁ  cation of proteins, with 
non-enzymic glycosylation (glycation) particularly associated with ageing. Glycation is initiated by the reaction of glucose with the amino group of lysine residues, which then proceed to form a Schiff SECTION 8  the psychiatry of old age

1509
base, and progressively more complex compounds collectively 
termed advanced glycosylation end (AGE) products. As little varia-tion was found in the glycation levels of lens crystallin proteins in subjects aged between 10 and 80 years, post-synthetic mechanisms may be as much an effect as a cause of ageing.
(e) Free radical damage
The role of free radicals  in ageing was ﬁ  rst proposed over 50 years 
ago.(13) A wide range of highly reactive free radicals are derived 
from molecular oxygen, including the superoxide and hydroperoxyl radicals, hydrogen peroxide, hydroxyl radical, and singlet oxygen. The polyunsaturated fatty acid side chains of cell and organelle membranes form highly susceptible targets for the action of reactive oxygen species (ROS) , and the resulting lipid peroxidation

can result in severe membrane damage and eventual death of the cell. DNA may also be a critical target molecule for free radical damage, with mtDNA especially susceptible because of its proxim-ity to the site of free radical production in the inner mitochondrial membrane.
(9) Although a wide variety of antioxidants have been 
identified in humans, including ascorbate, α-tocopherol, 
β-carotene, glutathione, and the enzymes superoxide dismutase, 
peroxidase, and catalase, there has been little experimental evidence that these antioxidants can produce a signiﬁ  cant extension in 
maximum lifespan. However, transgenic mice expressing the free radical scavenger enzyme catalase targeted to mitochondria showed an approximately 20 per cent extension in their mean and maxi-mum lifespans, and concomitant delays in cardiac pathology and cataract development.
(14)
Ageing as an energy crisis

(14)
From an evolutionary perspective, it was suggested that senescence was the end-result of an energy conservation strategy operating in somatic cells. During the course of a lifespan, total available energy has to be allocated to a variety of functions, including macromo-lecular synthesis and degradation, cell and organ maintenance, and reproduction of the species. Since the energy supply is ﬁ  nite, 
and to ensure propagation of the species by the successful trans-mission of genes to future generations, a compromise has to be reached between the energy made available for each of these func-tions. According to the disposable soma theory , this accommoda-
tion in energy saving is achieved by maintenance of absolute or near absolute accuracy in germ cell replication but less rigorous error correction in somatic cells.
(15)
As an organism ages, the demands placed on the free energy pool

(15)
As an organism ages, the demands placed on the free energy pool 
alter and increase from a primarily anabolic role to meeting the requirements of ever-increasing repair and catabolic functions, including those imposed by speciﬁ  c disease-related insults. If the 
mitochondrial inner membrane and/or mtDNA is damaged, an organism must increasingly rely on alternative, less efﬁ  cient path-
ways for its energy needs, ultimately resulting in a critical shortfall in the energy supply needed to sustain life. In such an energy crisis ,
the somatic cells primarily affected would be post-mitotic cells with high energetic demands, typiﬁ  ed by the heart, skeletal muscle, 
and the brain.
Dietary modiﬁ  cation of ageing
Inherited factors clearly play a major role in ageing, and in deter-
mining the human lifespan. But if ageing also is stochastic in nature then it should be possible to modify development of the ageing phenotype by altering the relative influence of contributory

mining the human lifespan. But if ageing also is stochastic in nature then it should be possible to modify development of the ageing phenotype by altering the relative influence of contributory 
environmental variables, including diet.
Dietary (or calorie) restriction, based on a diet reduced in total 
amount but otherwise nutritionally adequate, is the only method so far proven to increase maximum lifespan in mammals. The orig-inal dietary restriction experiments conducted in the 1930s result-
ed in animals that remained prepubertal as a result of their retarded 
growth and development.
(16,17) In more recent food restriction 
experiments, rodents have typically been fed a diet corresponding to approximately 60 per cent of the food ingested by ad libitum  fed 
controls, commencing either soon after weaning or in young adulthood. Under these circumstances, besides a increase in maxi-mum lifespan the development of tumours and other chronic diseases of late adulthood was slowed.

DNA microarray  studies into the effects of calorie restriction 
(CR)  in mice have indicated a shift in transcriptional patterns 
towards increased protein turnover and decreased macromolecular damage. Rats maintained on a restricted diet (representing 60 per cent of the control diet) for 36 weeks showed increased transcrip-tion of muscle genes involved in ROS scavenging, tissue develop-ment, and energy metabolism, with decreased expression of genes 
involved in signal transduction, stress response, and structural and 
contractile proteins.
(18) CR also was able to maintain ATP produc-
tion but at the same time reduce age-dependent endogenous oxidative damage.
(19)
Preliminary studies conducted on rhesus macaque monkeys 
aged approximately 20 years and maintained on a reduced caloric intake for 9–10 years have suggested that long-term CR produced beneﬁ  cial alterations in glycogen metabolism and mitigated the

aged approximately 20 years and maintained on a reduced caloric intake for 9–10 years have suggested that long-term CR produced beneﬁ  cial alterations in glycogen metabolism and mitigated the 
development of insulin resistance in older animals. Although restricted numbers of primates have been studied and few have attained extreme old ages, a wide range of potentially beneﬁ  cial 
outcomes have been reported, in particular an improvement in glucose tolerance, a lower core body temperature, an attenuated decline in dehydroepiandrosterone (DHEA) sulphate levels, decreased triglycerides and increased HDL2b, in combination with lower weight, lean body mass and fat, and lower energy expendi-ture (reviewed in Bittles 2008).
A number of small-scale human studies have been reported, 
including a 6-day investigation on eight adults and eight pubertal

including a 6-day investigation on eight adults and eight pubertal 
children involving a 50 per cent caloric reduction that resulted in a significant reduction in the nitrogen balance of both adults and children and a decrease in their insulin-like growth factor-1 (IGF-1) levels. Individuals who had voluntarily adopted a restricted food intake for 6 years displayed a wide variety of physiological, metabolic, and biochemical changes, all of which would be consist-ent with protection against atherosclerosis,
(20) and CR alone or 
with accompanying exercise regimes signiﬁ  cantly increased the 
numbers of mitochondria in skeletal muscle cells while decreasing both energy expenditure and the frequency of mtDNA damage in overweight healthy adults.
(21)
Ageing and the concept of healthy life 
expectancy
Active Life Expectancy (ALE) is deﬁ  ned as the period of life free of

(21)
Active Life Expectancy (ALE) is deﬁ  ned as the period of life free of 
disabilities which interfere with basic Activities of Daily Living (ADL), e.g. eating, getting in and out of bed, bathing and toiletry needs, dressing, and indoor mobility. The concept of healthy life expectancy has been extended by weighting speciﬁ  c physical and 8.1 the biology of ageing

1510 SECTION 8  the psychiatry of old age
cognitive dysfunctions to measure Disability-Adjusted Life Y ears 
(DALY) and Quality-Adjusted Life Y ears (QALY). Disability 
Adjusted Life Expectancy (DALE)  is now widely used in epidemi-
ological studies to estimate the number of years that might be expected to be spent in ‘full health’ . A common ﬁ  nding in devel-
oped countries was that although females enjoyed higher DALE scores they also could expect more years of disability at advanced ages. Although measures such as DALE, DALY, and QALY have been criticized on methodological grounds, given global increases in the numbers of elderly individuals, the concept of healthy life expectancy may be increasingly useful in identifying the health and support needs of the aged.
Discussion

As in other areas of medical science, the Human Genome Project has impacted strongly on research into biological aspects of ageing, and DNA analysis now offers major insights into the development of the ageing phenotype. During the last decade, DNA microarray studies have been adopted to investigate changes in gene expression that accompany ageing.
Initial studies on rodent tissue showed differential gene expression 
patterns with advancing age, indicative of a marked stress response and lower expression of metabolic and biosynthetic genes. An ‘age-ing transcriptome’ conserved across mammalian species has been identiﬁ  ed, comprising deregulation of mitosis, cell adhesion, trans-
port, signal transduction, mitochondrial function, and inﬂ  amma-
tory response, and accompanied by a reduction in processes dependent on energy metabolism and mitochondrial function.
(22)

(22)
Subsequent analysis of human tissue based on large-scale DNA microarrays has revealed diverse patterns of both increased and decreased gene expression. However, a study of ~32 000 muscle tissue genes obtained from volunteers aged 16 to 89 years conﬁ  rmed the 
existence of a common ageing signature, with altered levels of expression in 250 age-regulated genes and three genetic pathways that correlated both with chronological and physiological age.
(23)
Research on adult stem cells may provide key future insights into 
ageing. Adult stem cells mainly undergo chronological ageing, as in skeletal muscle, or exhibit a combination of chronological and replicative ageing, typiﬁ  ed by haematopoietic stem cells.
(24)
What remains to be determined is whether the overall decline in

(24)
What remains to be determined is whether the overall decline in 
tissue regenerative capacity with advancing age is caused by intrin-sic ageing of stem cells, or is due to increasing impairment of stem cell function in an aged tissue environment. Until this basic question is resolved, the prospect of stem cell therapy as a potential ‘treatment’ to correct the functional declines and degenerative diseases typical of human ageing will remain a theoretical possibility.
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et al. (2005). Extension 
of murine life span by overexpression of catalyse targeted to mitochondria. Science ,308, 1909–11.
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19. Lopez-Lluch, G., Hunt, N., Jones, B., et al. (2006). Calorie restriction 
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1511
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Nature Genetics ,441, 1080–6.8.1 the biology of ageing

8.2
Sociology of normal ageing
Research on the sociology of normal ageing has focused on under-
standing the paradigms of ‘ successful ageing ’ . In an apparent 
reaction to ‘ disengagement theory’(1) which proposed that to with-
draw from roles and relationships in old age was normal, a new conceptual framework was developed in the late 1960s and 1970s which attempted to explain how individuals adapted to the con-straints of ageing and old age. This has been variously measured in terms of good health, high levels of physical and mental function-ing, and active engagement with one’s social and physical environ-ment. While post-modernism and critical gerontology have attempted to refocus the debate, the emphasis of most research and writing has remained within the framework of understanding, explaining, and even facilitating, ‘success’ in old age.
There is also a body of research which recognizes the importance

There is also a body of research which recognizes the importance 
of the life course perspective , and that throughout an individual’s 
life, he or she is faced with continuities  and discontinuities  which 
have to be negotiated and resolved. Old age is but part of this life-
long process. Changes which occur in later life, such as retirement and widowhood, will lead to discontinuities in roles and relation-ships, other aspects of our lives will undergo little change allowing continuity. Alongside this, perspectives from anthropology, history and the social constructionist school of thought have also been recently inﬂ  uential.
This chapter will discuss concepts of age, generation, and cohort. 
It will consider the contribution of the life course approach to understanding ageing, and the manner in which other perspectives, such as social constructionism, narrative psychology and anthro-pology, have contributed to the sociology of normal ageing.
Structuring the life course through age

According to Hazelrigg,(2) the concept of age introduces 
signposts which link memory and anticipation, an iteratively remembered past and an iteratively expected future. Age classiﬁ  ca-
tion is thus integral to normal organization of consciousness. As Mead’s extensive work on life history, reminiscence and autobi-ography informs us,
one interacts retrospectively with one’s younger selves, recalling earlier states of selfhood in the productive functioning of memory, and interacts prospectively with ones’ older selves, anticipating conditions, actions, 
goal realizations and the like of late states of selfhood .
1
For both the individual and society, age conveniently dissects the 
life course into more manageable components. As a capitalist, industrial system emerged, and individuals moved from domestic units to bureaucratically organized corporations, so age was used to deﬁ  ne adulthood and thus labour force participation. Age

became the basis for regulating a large population. It deﬁ  ned the 
responsibilities of citizenship, and for each age related transition there is a stage of preparation, a stage of participation, and a stage of retirement.
Various anthropological studies
2 have highlighted alternative 
ways in which the life course might be structured. One of the most inﬂ uential anthropological studies on the sociology of ageing was 
Cowgill and Holmes
(3) work on ageing and modernization, which 
argued that the marginalization of older people was directly linked to modernization. While extensively debated ever since, this work highlighted the importance and complexity of cultural diversity. The burgeoning of anthropological studies around the concept of age and ageing since the Cwgill and Holmes study have contributed signiﬁ  cantly to our understanding of this diversity.
Neither the !Kung nor Herero, hunter-gather and Bantu

Neither the !Kung nor Herero, hunter-gather and Bantu 
pastoralist peoples respectively of Botswana, have a concept of chronological age, marking age by physical transitions. Alternatively, the Tuareg, a semi-nomadic peoples in northern Niger, noted age by social transitions—courtship, marriage, childbirth, and grand-children. Here, life transitions deﬁ  ning the ageing process are 
predominantly social rather than biological. A girl becomes 
a women not at menstruation, but at marriage; a women becomes 
an older women not at menopause but on having a child marry. For the Sukama of north-west Tanzania, ageing is deﬁ  ned through

an older women not at menopause but on having a child marry. For the Sukama of north-west Tanzania, ageing is deﬁ  ned through 
life course events. This emphasizes the social status of elderhood, measured by the wealth of alliances, offspring and livestock, which could not be diminished through ill health or loss of mental capacity. The Gussui of south-western Kenya have a similar notion of elderhood. However, they have adapted this traditional seniority gradation based on networks and afﬁ  liations to modern demands, 
1 G.H. Mead, quoted in Hazelrigg p. 105(2)
2 See Harper for a full reference list to these studies(5)

1513
incorporating such aspects as the role of entrepreneur to the 
criteria for achieving successful seniority status.
Modern Japanese society still applies a wide variety of terms to 
different points of the life course indicating complex relationships between chronological age and life transitions and physical appearance. For example, mid-life men and women w ith children 
whether or not they are married, will commonly be referred to as 
uncle and aunt, ( oji-san  and oba-san ). Similarly, old men and women 
are frequently given the name of grandfather or grandmother, ( ojii-
san and obaa san ) regardless of the presence of grandchildren, 
a characteristic also found in some European countries such as Greece. It is therefore clear that the domination of chronological age, has less salience in some other cultures.
Generation and cohort

Two further important concepts are generation and cohort. Individuals born within the same time period may be perceived as having a shared history and a common biography. The concept of generation  is thus the link between an individual life course 
and the social changes that occur during the historical time of that life course. A generation may thus be thought of as embodied 
history .
Many of these draw on ideas from Mannheim who explored the

history .
Many of these draw on ideas from Mannheim who explored the 
creation of society through the continuous emergence of new age groups or generations. He argued that if social processes were always carried on and developed by the same individuals then once established, any fundamental social pattern, attitude or intellectual trend would probably be perpetuated. Culture was thus developed by individuals who come into contact anew with the accumulated heritage, that is the role of generations and while the continuous 
emergence of new individuals results in some loss of accumulated 
possessions it facilitates re-evaluation of our inventory and teaches us both to forget that which is no longer useful and to covet that which has yet to be won.
The problem for quantitative social scientists is how to disentangle 
those factors pertaining to the individual life course from those 
emerging from the historical context. It is here that the concept

emerging from the historical context. It is here that the concept 
of cohorts, and cohort analysis has been reﬁ  ned by some to form 
a more analytical tool in the understanding of age and generational change.
A cohort begins with a particular demography at birth, that is its 
sex, race and economic composition. Differential mortality may lead to a higher proportion of some sub-groups surviving to old age; social mobility may lead to changes in cohort social status 
composition; and different historical periods will allow or enhance differential migration in and out of speciﬁ  c cohorts. A more sophis-
ticated analysis places cohorts within speciﬁ  c historical contexts.
(4)
The life-stage principle  suggests that disruptive social changes have 
enduring consequences on the subsequent lives, a particularly marked effect on those vulnerable at the time of occurrence.
Life course perspective

The life course perspective views old age as part of a life-long process of continuity and change. These can be addressed within four main frameworks: context, transitions, roles , and 
relationships .Context
A starting point for life course analysis is the acknowledgement 
of the historical context  within which different cohorts experience 
different aspects of the life course to life course perspective. As Harper
(5) explores, while, most older men experienced a long

(5) explores, while, most older men experienced a long 
period of economic activity followed by abrupt retirement, many older Western women experienced their younger lives within a framework of primary domestic duties, supplemented by intermit-tent economic activity. As a result, most older women replaced low earning capacity or economic dependence in younger life, with low incomes in old age. Cohorts in mid life, however, have had very dif-ferent social and economic frameworks within which to live out their lives. Half the labour force in many countries is now female and full-time economic employment, with or without domestic, in particular childcare responsibilities, is becoming a widespread experience for many women. Despite this, there are still considera-ble income disparities in earning capacity of mid-life men and women. However, it is likely that future cohorts of older women will have higher incomes relative to older cohorts, and a lower gen-der income disparity.
Transitions

The processes which occur within these contexts can be understood as a series of life transitions.
(6) Key transitions associated with later 
life are the end of active parenting, grandparenthood, widowhood and retirement. Each of these phases of life which may overlap, may be understood in relation to prior phases, and are mediated by other variables such as gender, class, and race. The transition to grandparenthood, for example, is experienced very differently by men and women, while the end of active parenting and transition to parent of a non-dependent child, the so-called empty nest 
syndrome , is mediated both by gender and by the experience of 
active parenting itself.
The transition to widowhood  is one of the most stressful events 
of later life, with a high prevalence of depression both immediately before (presumably due to anticipation of the event and/or associ-ated care giving) and in the ﬁ  rst year following bereavement.

of later life, with a high prevalence of depression both immediately before (presumably due to anticipation of the event and/or associ-ated care giving) and in the ﬁ  rst year following bereavement. 
Widowhood is likely to lead to lower income but higher social 
contacts for women, while men maintain their income, but are 
more likely to lose social contacts, unless they remarry. Over half women over 65 are widowed, rising to four-ﬁ  fths at 85. Only 17 per 
cent of men are widowed over 65, rising to 43 per cent by their late 80s. Nearly three-quarters of older men in the UK are married, compared with less than a half of older women. This is explained both by differential life expectancy and the tendency of men to remarry following divorce or widowhood.
(7)
The transition to Grandparenthood  is the current normal experi-

(7)
ence of old age. US data suggests that more than half the popula-tion aged over 55 are in four-generation families and three-quarters of this population are or can expect to be as grandparents, with a prediction that one-third of current grandparents will live to be great grandparents, and one-ﬁ  fth of all women who reach 80 
will spend some time in a ﬁ  ve-generation family as great-great-
grandmothers. A similar picture may be found in the UK with estimates that three-quarters of adults over 66 years of age are grandparents. The transition from parenthood to grandparent-hood, and even great-grandparenthood, determines both an individual’s self-identity and subsequent roles and functions as 8.2 sociology of normal ageing

SECTION 8  the psychiatry of old age 1514
grandparenthood. In addition, the experience of the relationship 
that the grandchild has with his or her grandparent earlier will partially determine the way they take on the role and relate to their own grandchildren later on in life. Other sociological theories have been applied to the study of grandparenthood. Role theory  suggests 
that a successful transition to grandparenthood requires both some socialization to the role, and appropriate life course timing. Social stress theory  is used to argue that stress associated with 
transition to grandparenthood is related to the number, type, and context of the transitions and moderated by gender, education, income, and race.
(9)
For many individuals, especially men, the transition to retirement
is abrupt. Although early retirement has increased in Europe over the past twenty ﬁ  ve years, most men still retire from full time work

is abrupt. Although early retirement has increased in Europe over the past twenty ﬁ  ve years, most men still retire from full time work 
in their early-to mid-60s. A successful transition to retirement requires securing both ﬁ  nancial security and personal adjustment. 
Atchley
(10) identiﬁ  es several phases of retirement. Pre-retirement, 
which may include a combination of both negative and positive feelings towards the impending event; a honeymoon period imme-diately following the event, which may extend for several years depending on the adjustment and resources, social, ﬁ  nancial, and 
personal, available to the individual; disenchantment and reorien-tation; and eventually (if successful) stability. This latter stage occurs with the development of a well established set of criteria for making choices and dealing with the challenges and opportunities of this new life phase.
Roles and relationships

The above transitions—retirement, widowhood, grandparenthood - are also, of course, phases of life with speciﬁ  c roles and relation-
ships. Thus, the transition of retirement also has an associated phase of being retired; that of grandparenthood of being a grand-parent; that of widowhood of being a widow or widower.
We can examine two of these—late-life parenting and grandpar-
enting—in the context of negotiating transitions and continuities in family roles and relationships as individuals age.
(11) Intergenera-
tional solidarity—shared values, normative obligations and endur-ing ties—and intergenerational conflict—whereby issues are resolved and relationships move on have been long seen as impor-tant components of this. More recently the concept of intergenera-tional ambivalence has been introduced. This, it is argued, reﬂ  ects

the contradictions which occur with ageing within family relation-ships These arise both through the desire of parents and children for both help and freedom, and conﬂ  icting norms regarding family 
relationships especially around the issue of care giving.
(a) Late-life parenting
Increasing longevity also means that most parent-child relation-ships will be lived out as predominantly non-dependent adult dyads, this is despite the delaying of child birth. The common expe-rience for many parents and children is around 60 years of joint life, of which under one-third is spent in the traditional parent/dependent-child relationship. Around one-quarter of UK women and nearly 40 per cent of US women aged 55–63 still have a surviv-ing parent. These women have thus spent around 60 years a child, some 40 of them in an adult relationship with a living parent. This relies on re-bonding  in adulthood sometimes also referred to as 
‘reverse bonding’ .

(12)Under such experiences we see a loosening of 
the association between marital and parental roles. As the common experience of parenthood moves to more than 50 years of shared 
life, parents and children are adjusting to spending most of their relationship as independent adults. Similarly, husbands and wives are spending fewer of their joint lives as parents of young children. Relationships which have been historically based on a hierarchy which existed in part to support successful reproduction must move to greater equality, both child-parent, and husband-wife, as traditional roles based on parenthood give way to companionate relationships.
(12)
(b) Grandparenting roles3
Currently, women can expect to become grandmothers in their 50s and 60s due to the early ﬁ  rst age of births in the 1960s and 1970s.

(12)
Currently, women can expect to become grandmothers in their 50s and 60s due to the early ﬁ  rst age of births in the 1960s and 1970s. 
In addition, grandparental roles are lasting far longer due to increased longevity, the grandparent is thus more likely to be able to build a relationship with their grandchild into their adulthood. As a result many grandmothers, in particular, now face simultane-ous demands as children of frail and dependent parents, mothers and grandmothers, as well as still being in full or part time economic employment.
(13)
Grandmothers, in particular maternal grandmothers, are repeat-
edly attributed with having more inﬂ  uence in almost every value 
domain over their grandchildren than grandfathers. Research into the role of grandfathers has been limited.
(14) However, it has been

(14) However, it has been 
proposed that men become more nurturing as they get older and it could be hypothesized that these qualities might be expressed in relationships with their grandchildren. Similarly, the need to consider grandfathers as important resources for teenage mothers who are rearing their children, has been stressed. Harper also found that grandfathers could act as replacement partners and replace-ment fathers in female single parent households.
(13)
Various roles of grandparenthood have been identified.(15) 
Bengtson (1985) for example, identiﬁ  es ﬁ ve separate symbolic func-
tions of grandparents: being there; grandparents as national guard; family watchdog; arbiters who perform negotiations between (fam-ily) members; and participants in the social construction of family history. Harper’s study of grandmothers identiﬁ  es grandmother as

carer, replacement partner (conﬁ  dante, guide and facilitator), 
replacement parent (listener, teacher and disciplinarian), and as family anchor (transferring values, attitudes and history).
(13)
Complementary perspectives
Our understanding of ageing from a life course perspective has drawn on valuable insights from narrative gerontology and the social constructionist perspective.
Narrative gerontology
Narrative gerontology’s main contribution to the ﬁ  eld of ageing 
has been to the role of the life story in the development of theoreti cal 
and empirical approaches to ageing. It presumes that individuals think and act on the basis of stories, which have an external 
structure and an internal reality. Individuals retell their stories as they progress through their lives to make sense of their lives, and

structure and an internal reality. Individuals retell their stories as they progress through their lives to make sense of their lives, and 
from a sociological perspective this retelling when carried out publicly provides considerable insights into various aspects of an individual’s experience of ageing across the life course. There are 
3 A full reference list on grandparenthood may be found in Harper.(5)

1515
four dimensions to this: the structural story, which reﬂ  ects the 
wider societal context inhabited across the life course; the socio-cultural story, which reﬂ  ects other identities such as ethnicity 
and gender; the situational story which reﬂ  ects an individual’s roles 
and relationships; and the interpersonal story, the meanings which the individuals place themselves on their life story.
Writers in this genre of theory have further suggested that indi-
viduals experience two types of time. Achenbaum
(16) describes this 
as a physical outer time  and a psychological inner time , or as Kenyon 
and Randall(17) state clock time  and story time . There may be a ten-
sion between the two types of time described as on time  and off 
time .(18) Hazelrigg(19) suggests that the tension between the two

time .(18) Hazelrigg(19) suggests that the tension between the two 
times has been become more extreme within modern society, so dominated by rigid timekeeping. He argues that modern life is lived in two separate registers. On the one hand, most of a life experience is formed directly and indirectly in a highly standardized sequence of institutionalized events—schooling, work, parenting, retirement. These events are regulated by procedural rules and recognized rou-tines, with predictable durations and regulated transitions between events. On the other hand, those aspects of life experiences that are not institutionalized and structurally stabilized in recognized life course sequences tend to have little or no connection to status dimensions or speciﬁ  c locations in the life course. These would 
include self-image, personal satisfaction, existential aesthetics etc.

T ensions arise when the two registers fail to coincide— off 
time .
(18) Examples include middle-aged couples falling in love and 
publicly exhibiting displays of physical affection and romance, or older people adopting student style lives. Off time may also include the experience of being externally forced, through illness for exam-ple, to fall outside the normal behaviour range as deﬁ  ned for one’s 
age. This also includes examples where society takes an individual and places them within a situation which is unusual for their chronological age–for example, a very young person being rapidly promoted within an institution which is very highly age regulated, such as a university, and taking on a professorial mantle.
Social constructionist approaches

The sociology of ageing has also recently enveloped social con-structionist approaches, including phenomenology, symbolic interactionism, and ethnomethodology. These approaches share a subjective orientation to social reality, focusing on describing how individuals negotiate their worlds, rather than trying to explain why. A key area of interest here is the management of identity across the life course and in particular as we age. Examples include, Matthew’s
(20) seminal work using symbolic interactionist 
approaches to explore how old women negotiate their own identi-ties when they are continually deluged with negative public stere-otypes of inﬁ  rmity and worthlessness. This is a theme taken up 
later by Featherstone and Hepworth
(21) in their work on the Masks 
of Ageing. Similarly, Karp(22) uses symbolic interactionist

of Ageing. Similarly, Karp(22) uses symbolic interactionist 
approaches to explore the impact of social messages on the emerg-ing consciousness of men and women in their 50s of their own ageing.
The sociology of, so-called, normal ageing thus combines perspec-tives from diverse traditions of thought. This actual measurement of ageing, in terms of health, physical and mental functioning, and active engagement with one’s social and physical environment,

has combined quantitative social science, epidemiology and politi-cal economy. The understanding of these interactions, draws on perspectives from sociology, psychology, and anthropology. In both cases, however, there is now recognition of the importance of context and process, and that, in reality, there is perhaps no single construct of ‘normal’ ageing. Given this perspective, it is essential that care for older adults is person-centred rather than imposed by professionals.
Johnson, M., Bengtson, V ., Coleman, P .  et al . (eds) (2005) The Cambridge 
Handbook of Age and Ageing . Cambridge University Press, 
New Y ork.
Ageing Horizons: http://www.ageing.ox.ac.uk/ageinghorizons/index.htm
Binstock, R. and George, L. (2005). Handbook of Ageing and the Social 
Sciences . Elsevier, London.
 1. Cumming, C., and Henry, W. (1961). Growing Old , New Y ork Basic 
Books.
 2. Hazelrigg, L. (1997). On the importance of Age. In Studying aging and

Books.
 2. Hazelrigg, L. (1997). On the importance of Age. In Studying aging and 
social change: conceptual and methodological issues  (ed. M. A. Hardy). 
pp. 93–128. Sage Publications, Thousand Oaks.
 3. Cowgill, D. and Holmes, L. (eds.) (1972). Ageing and Modernization ,
New Y ork, Apple Century Crofts.
 4. Elder, G. H., and O’rand, A. M. (1995). Adult lives in a changing 
society. In Sociological perspectives on social psychology
(eds. K. S.Cook, G. A. Fine, & J. S.House), pp. 452–475. Allyn and Bacon, Boston.
 5. Harper, S. (2006). Ageing Societies . Hodder Arnold, London.
 6. Elder, G. H. (1985). Perspectives on the life course. In Life course 
dynamics: trajectories and transitions  (ed. G. H. Elder)  1968–1980 .
pp.23–49. Cornell University Press, Ithaca.
 7. Arber, S. Davidson, K. and Ginn, J. (eds.) (2003). Gender and Ageing:

 7. Arber, S. Davidson, K. and Ginn, J. (eds.) (2003). Gender and Ageing: 
changing Roles and Relationships , Maidenhead, Open University 
Press.
 8. Kornhaber, A. (1996). Contemporary Grandparenting , New York, 
Sage. 
 9. Szinovacz, M. (1997). Grandparents today: a demographic proﬁ  le. The
Gerontologist, 38, 37–52.
10. Atchley, R. (1989). A continuity theory of normal aging, The
Gerontologist, 29, 183–90.
11. Giarrusso, R., Silverstein, M., Gans, D., et al.  (2005). Ageing parents 
and adult children: new perspectives on intergenerational relationships. In The Cambridge handbook of age and ageing (eds. M.L. 
Johnson, and V . L. Bengston). Cambridge University Press, 
New Y ork.
12. Harper, S. (2006). Ageing Societies . Hodder Arnold, London.
13. Harper, S. (2005). Understanding Grandparenthood. In The Cambridge

New Y ork.
13. Harper, S. (2005). Understanding Grandparenthood. In The Cambridge 
handbook of age and ageing (eds. M.L. Johnson, and V . L. Bengston), 
14. Mann, R. (2007). ‘Out of the shadows?: Grandfatherhood, age and 
masculinities’ , Journal of Aging Studies , 21(4), 271–81.
15. Bengtson, V . (1985) Diversity and symbolism in grandparental roles. 
In Grandparenthood  (eds. V . Bengtson, and J. Robertson) Beverly Hills, 
Sage.
16. Achenbaum, W. A. (1991) Time is the messenger of the Gods: a 
gerontological metaphor. In Metaphors of Aging in Science and 
Humanities (eds.  G. Kenyon, J. Birren, and J. Schroots), pp. 83–101. 
New Y ork, Springer.8.2 sociology of normal ageing

SECTION 8  the psychiatry of old age 1516
17. Keynon, G., and Randall, W., (1997). Restorying our Lives: 
personal growth through autobiographical reﬂ  ection . Westport, CT, 
Praeger.
18. Hagestad, G. O. (1986). Dimension of time and the family. American 
Behavioral Scientist ,29, 679–94.
19. Hazelrigg, L. (1997). On the importance of Age. In Studying aging and 
social change: conceptual and methodological issues  (ed. M. A. Hardy), 
pp. 93–128. Sage Publications, Thousand Oaks.20. Matthews, S. (1979). The Social World of Older Women . Newbury park, 
Sage.
21. Featherstone, M., and Hepworth, M., (eds.) (1995). Images of Ageing .
22. Karp, D. (1988). A decade of reminders: changing age consciousness 
between ﬁ  fty and sixty years old, The Gerontologist , 727–38.

8.3
The ageing population and 
the epidemiology of mental 
disorders among the elderly
In the last decades the ageing of the populations has become a 
worldwide phenomenon.(1) In 1990, 26 nations had more than 
2 million elderly citizens aged 65 years and older, and the projec-
tions indicate that an additional 34 countries will join the list by 
2030. In 2000, the number of old persons (65+ years) in the world 
was estimated to be 420 million and it was projected to be nearly 1 
billion by 2030, with the proportion of old persons increasing from 
7 to 12 per cent.(2) The largest increase in absolute numbers of old 
persons will occur in developing countries; it almost triples 
from 249 million in 2000 to an estimated 690 million in 2030. The 
developing regions’ share of the worldwide ageing population will 
increase from 59 to 71 per cent. Developed countries, which 
have already seen a dramatic increase in people over 65 years of

have already seen a dramatic increase in people over 65 years of 
age, will experience a progressive ageing of the elderly population 
itself (see Fig. 8.3.1). The global trend in the phenomenon of 
population ageing has dramatic consequences for public health, 
health care ﬁ  nancing, and delivery systems in the whole world. The 
absolute number of chronic diseases as well as psychiatric disorders 
is expected to increase. In this chapter, the epidemiological aspects 
of the most common psychiatric disorders of the elderly are 
summarized and discussed.
The epidemiology of depression in the elderly can be approached 
at three levels: its occurrence in the elderly living in the community, 
in those reaching primary care, and in the residents of hostels and 
nursing homes.
The community

It might be expected that, overall, the prevalence of depressive 
symptoms and disorders might increase in old age due to the loss 
of partners, friends, social status, retirement, income, and, above 
all, declining health. It is surprising, therefore, that surveys of the 
elderly in the general population have recurrently found rates that 
are signiﬁ  cantly lower than in younger adults. Many of the large 
national surveys have not included persons aged over 65 years, but 
two exceptions are Australia, which found a 12-month prevalence 
of 1.7 per cent for the 65 years and over group compared with 5.8 per cent for all adults; and the New Zealand survey with rates 
of 2.0 and 8.0 per cent, respectively. It must be emphasized that 
these data refer to depressive symptoms in the elderly living in the 

What is so far unproven is that such ﬁ  ndings are indeed valid, 
and if they are, what might explain them.(3) They could be due to 
sample bias, in which elderly respondents with depressive symp-
toms may be more likely to decline to be interviewed than younger 
depressed people. Selective mortality has also been proposed, but 
cannot account for the size of the difference. It could be due to an 
error in case ascertainment, by which the interview instrument is 
not equally valid across age groups. For example, questions about 
depressive symptoms may be responded to differently by persons 
aged 20 and 80 years. Another possibility is a cohort effect in much 
of the Western world, where people born in the second half of the 
twentieth century have higher rates for depression.(4,5) This seems

twentieth century have higher rates for depression.(4,5) This seems 
increasingly likely and may be due to a combination of social and 
Fig. 8.3.1 Percentage of the population aged 65+ for more developed and 
less developed countries. (Reproduced from Kinsella, K. and Velkroff, V.A. The 
demographics of aging. Aging Clinical and Experimental Research , 4, 59–69, 
copyright 2002 with permission from Editrice Kurtis S.r.l.)

SECTION 8  the psychiatry of old age 1518
Unsurprisingly, the prevalence of depressive symptoms is consider-
ably higher in elderly persons consulting their doctor than in the general community. One study in London found a point prevalence of about 30 per cent. Where it has been possible to compare the rates for those cases recognized by their doctor with cases indepen-dently ascertained by a research measure, such as a screening instrument or standardized interview, a typical ﬁ  nding is that the 
general practitioner recognizes about two thirds of the mild cases, rising to some 90 per cent of the moderate to severe ones. Some cases are considered to be depressed when they are not. Another ﬁ nding is that elderly persons with depressive symptoms may not 
mention them to their doctor, attributing them to their age and circumstances. These ﬁ  ndings have led to programmes offering

mention them to their doctor, attributing them to their age and circumstances. These ﬁ  ndings have led to programmes offering 
additional training for GPs and to recommending the use of brief screening tests in primary care. Because diagnosis would lead to appropriate treatment being given earlier in an episode of depres-sive disorder, its duration would be shortened. Since prevalence is the product of incidence and duration, the prevalence of depres-sion would therefore be expected to fall. This is an example of the application of epidemiology to prevention, which is its ultimate service.
Depression in hostels and nursing homes

Prevalence rates are also higher in hostels and nursing homes. In the United States, levels as high as 30 to 50 per cent have been reported. It might be thought that the context of living in a nursing home would account for having depressive symptoms. But one study found that the excess over the general population rates was largely accounted for by medical disorders, environmental factors contributing little to the variance. This needs to be studied further because it seems counterintuitive that the social and physical environment, both of which can be modiﬁ  ed, could be of little 
relevance.
What is important is that only about one quarter of cases are 
recognized. T o compound the situation, those cases that are recog-nized tend to be treated with too low doses of antidepressants. Depressive symptoms are well known to occur comorbidly with 
cognitive decline and the dementias. These ﬁ  ndings from clinical

cognitive decline and the dementias. These ﬁ  ndings from clinical 
epidemiology have pointed to the need for better case recognition through education of medical and nursing staff, and to the use of routine screening of residents in such settings.
Suicide
For many decades across the world, the traditional pattern has been for the highest rates of suicide to be in elderly men. This has now changed. In over a third of countries, both developed and less developed, it is younger people who have come to carry the highest rates. The World Health Organization provides a valuable resource for such data, showing rates by age and gender for nearly all coun-tries from 1950 onwards.
(6) The pattern varies considerably

(6) The pattern varies considerably 
between countries. For example, in the United Kingdom in 2002, men aged 75 and over had a rate of 10 per 100 000, whereas the highest rate was 18 per 100 000, in men aged 35–44 years. In the United States and in the Russian Federation, the rates for men aged 75 and over were 41 and 89 per 100 000, respectively.
The main risk factors for suicide in the elderly are a past history 
of an attempt, depressive disorder, physical illness or disability, chronic pain, recent losses, social isolation, and access to lethal 
means. While universal interventions are more powerful than selected factors in prevention,
(7) these attributes can be used in

(7) these attributes can be used in 
selective intervention to identify groups at increased risk. Furthermore, being multiplicative, these markers are of great value in individual cases by alerting the clinician to a person needing particular attention. Here is another example of the use of epide-miology for prevention. A systematic review of suicide prevention strategies for all age groups concluded that two interventions did reduce rates: physician education in recognizing and treating depression; and restricting access to lethal means.
(8) Both of these 
interventions have close relevance to the elderly.
The subject matter here refers to older people who have enduring attitudes and behaviour that bring difficulties for themselves or for others.
(9) There is only sparse information on the pre-

valence of personality disorders in the general population, let alone speciﬁ  cally in the elderly. One exception, based on a national sur-
vey of mental health, found a lifetime prevalence of 6.5 per cent across all age groups with a trend towards lower rates with increasing age.
In clinical practice, it has long been suggested that traits such as

In clinical practice, it has long been suggested that traits such as 
impulsivity and externalizing behaviours tend to become less fre-quent in later life, whereas anxiety-prone, dependent, schizoid, paranoid, or obsessional persons are likely to change little as they age, or to become more so. Bergmann’s pioneering enquiries among the elderly of Newcastle upon Tyne found that it was the anxiety-prone and insecure types that had late-onset neurotic disorders. A more recent study of late-life depression found an overall preva-lence of comorbid personality disorder of 10–30 per cent. The group formerly known as neurotic and more recently as Cluster C in the DSM classiﬁ  cation, had the higher prevalence. The Cluster B group,

those with borderline, narcissistic, histrionic, and antisocial traits, were rare. What is not yet established, however, is if this lower prev-alence also exists in the general population of the elderly, not just among cases with depressive disorder who have reached treatment in specialist services.
The epidemiology of personality disorders in later life is there-
fore signiﬁ  cant for two reasons. First, some types are associated 
with increased risk of anxiety, depression, or paranoid states ( vide 
infra ). Second, there remains much yet to understand about the 
natural history of the personality disorders across the lifespan.
Psychosis of late onset
For the functional psychoses of late life, epidemiological informa-tion comes from two sources: studies of persons who have reached psychiatric services; and surveys of elderly persons living in the general community.
(10) Psychotic symptoms probably exist as a

(10) Psychotic symptoms probably exist as a 
continuum of severity, with only the more developed cases meeting diagnostic criteria. These often, but not always, reach psychiatric services, not uncommonly through being brought to the attention of the police. States phenomenologically similar to those found in clinics do occur in the community in non-trivial numbers. For cases that reach the threshold for a diagnosis by virtue of the range and severity of symptoms and behaviour, it has been proposed that cases with onset after the age of 60 years be called ‘very-late-onset schizophrenia-like psychosis’ . The syndrome has a 1-year prevalence

1519
of 0.1 to 0.5 per cent. For advancing knowledge about the aetiology 
of schizophrenia, any information on it might be useful in explain-ing why people with this syndrome have reached the seventh decade or later in life without becoming psychotic, and only then develop it. It is more common in women. This is unlikely to be due to different social visibility or access to services. It is asso-ciated with a better premorbid level of social and occupational functioning. Premorbid paranoid or schizoid traits have been implicated and both clinical and community-based studies have found an association with sensory impairment such as deafness or poor eyesight. Personal and environmental factors associated with ageing have been considered, such as physical ill health, bereave-ment, loss of friends, and loss of income, but these have not been shown to contribute signiﬁ  cantly. Genetic factors appear to be less 
important than in earlier onset schizophrenia.
Alcohol and drug dependence

It is generally believed that the prevalence of alcohol abuse and

It is generally believed that the prevalence of alcohol abuse and 
dependence declines during adult life and that the elderly have low rates in most communities. This may well be the case, but some other factors have to be considered. Whatever the prevalence, the absolute numbers will rise in the future because of the unprecedent-ed growth in the elderly population. Next, the assumption may be false. In community surveys, errors in the ascertainment of alcohol abuse may lead to an underestimate for older persons. Most screen-ing instruments were developed for use on younger adults, so their validity in the elderly is largely undetermined. Measures of the quantity drunk may mislead because smaller amounts may have an intoxicating effect in persons whose body fat, lean tissue, cerebral reserve, and metabolic function have declined. So the usual cut-off for problem drinking may be set too high for the elderly. One review

of screening instruments concluded that the CAGE and MAST-G 
scales were appropriate, whereas other widely used instruments were not.
(11) Next, all the studies have been cross-sectional. The 
elderly may have lower rates because of a cohort effect, whereby people born in the ﬁ  rst half of the twentieth century may have been 
more moderate drinkers for all their life, compared to the high levels of consumption that are now found in the young of both sexes.
The actual values for prevalence are dependent on the instru-
ment used and the deﬁ  nition used to deﬁ  ne problem drinking, 
alcohol abuse, or dependence.
(12) One review of community studies 
gives a ﬁ  gure of 5.1 per cent using various deﬁ  nitions. Invariably, 
men have higher rates than women. There is also considerable vari-ation between countries and across different cultures. In identifying cases, a distinction of clinical signiﬁ  cance needs to be made between

late-onset and long-standing alcohol abuse. In primary care, accident and emergency departments, hospital in-patients, and nursing homes, the prevalence is much higher, yet cases are consistently under-recognized. The use of screening instruments in all of these settings has been advocated to improve this.
Alcohol abuse carries important comorbidity. In addition to all 
the established medical complications, it is associated with falls, subclinical delirium, cognitive decline, and depression. One study demonstrated a ﬁ  ve-fold increase in the risk of developing a psy-
chiatric disorder, especially depression and dementia. Simultaneous 
use of benzodiazepines, itself common in older persons, is clearly 
an additional and important factor. Against all this, it should be recalled that moderate alcohol use has been found in population studies to be associated with better mental and cardiovascular 
health, as well as being subjectively enjoyable.
Alzheimer’s disease and other dementias

In the last two decades the dementia ﬁ  eld has registered a tremen-
dous scientific progression in many research areas including aetiology, pathogenesis, clinical aspects, treatment, and prevention. These advances have opened new perspectives, especially concern-ing deﬁ  nitions and diagnostic criteria, which have a relevant impact 
on epidemiological research.
Dementia is still deﬁ  ned as a syndrome which includes memory 
deﬁ cits and disturbance of other higher cortical functions; these 
major symptoms are commonly accompanied, and occasionally preceded, by deterioration in emotional control, social behaviour or motivation. However, it has become apparent that memory impairment may not necessarily be the major or ﬁ  rst symptom for 
dementia subtypes such as frontotemporal dementia (FTD) and vascular dementia (VaD). Furthermore, as the current deﬁ  nition

dementia subtypes such as frontotemporal dementia (FTD) and vascular dementia (VaD). Furthermore, as the current deﬁ  nition 
requires impairment severe enough to interfere with daily func-
tioning, in several cases a delay of the diagnosis occurs. For that reason, a new research line has emerged with the aim to detect early Alzheimer’s disease (AD) and other dementias, and the terms mild cognitive impairment (MCI) and cognitive impairment 
no-dementia (CIND) have been proposed to identify those subjects 
that show a clear cognitive deﬁ  cit but do not fulﬁ  l diagnostic crite-
ria for dementia. Finally, it is well known that dementia syndrome can be induced by many different underlying diseases, and that a differential diagnosis may be difﬁ  cult for several reasons. AD as

well as other dementia subtypes shows heterogeneity with distinct clinical and pathological characteristics; many different dementing disorders overlap in clinical and pathologic features; and different dementing disorders may make a common contribution or interact in causing dementia symptoms. Thus, rather than viewing, for example, AD and VaD as dichotomous entities, it may be more relevant to consider the role of their additive or synergistic interac-tions in producing a dementia syndrome.
(13,14)
Following these new perspectives, in this chapter we will sum-
marize the major ﬁ  ndings from the most recent epidemiological 
research according to three major topics: early detection of AD and other dementias, incidence and risk factors for AD and dementia, and prevalence and impact of the dementing disorders at the individual and societal levels.
Early detection

As diagnostic criteria for AD require gradual onset of cognitive deﬁ cits, it is expected that cognitive disturbances are present 
already before the diagnosis can be rendered. Cognitive deﬁ  cits are 
observable up to 10 years before dementia diagnosis with a sharp decline more evident in the ﬁ  nal 3 years,
(15) and occurring in 
episodic memory as well as in other cognitive domains such as executive functioning, verbal ability, visuospatial skills, attention, and perceptual speed.
(16) However, our capability to use such early 
disturbances as a predictive tool of incipient dementia is strongly limited by several concomitant facts: (1) cognitive decline is 
also present as a function of the normal ageing process; (2) several conditions other than AD may lead to cognitive disturbances in the elderly; and (3) dementia-free patients with cognitive impairment observed in specialized clinical settings are different from cogni-

tively impaired persons detected in the general population.
(17)8.3 the ageing population and the epidemiology of mental disorders among the elderly

SECTION 8  the psychiatry of old age 1520
T o overcome these difﬁ  culties, different deﬁ  nitions have been pro-
posed, with MCI and CIND being the most commonly used. MCI 
deﬁ nition was originally derived in a clinical setting to identify sub-
jects with isolated memory loss (now referred to as the ‘amnestic’ type) who may be in a preclinical phase of AD. Since then, the view has widened to cover a broader range of cognitive disturbances, and 
other MCI subtypes have been proposed.
(18,19) CIND is derived 
essentially from population-based studies, and operationalized in 
slightly different items. Unfortunately, not one of the proposed deﬁ  -
nitions has shown a sufﬁ  ciently good predictivity at the community 
level. Even a highly selected algorithm including subjective memory 
complaints, and global, and speciﬁ  c (memory/language) cognitive 
deﬁ cits could identify only 18 per cent of the incipient AD cases.(20, 21)

Although elderly persons with cognitive impairment have a high risk 
of developing dementia with a rate of about 11 to 50 per cent over 
1 to 5 years, not all persons w ith CIND or MCI develop dementia. 
A substantial proportion of these persons (24–42 per cent) even 
improve in their cognitive performances over time.(22) This diverse 
prognosis supports the notion that AD is not the only causal mecha-nism underlying cognitive impairment in the non-demented elderly 
population. Cognitive psychologists have detected lower cognitive 
performances in elderly persons with deﬁ  ciency in vitamin B
12 and 
folate, elevated homocysteine, thyroid stimulating hormone deﬁ  cien-
cy, and cardiovascular disease. Physicians found an association 
between CIND and a number of factors including frailty-related fac-

tors such as history of hip fracture and high consumption of multiple drugs, history of psychoses, and depressed mood occurring 3 years 
before CIND development.
(23) Other studies have identiﬁ  ed older 
age, low education, depression, APOE ε4 allele, medicated hyperten-
sion, mid-life elevated serum cholesterol, and high diastolic blood 
pressure, as well as diabetes and anticholinergic medication use as risk factors for MCI.
(17)
The prevalence of cognitive impairment—no dementia varies 
depending on diagnostic criteria with a maximum of 30 per cent.(24)
In the younger elderly (e.g. 65–75 years old) cognitive impairment is actually more frequent than dementia disorders.(25) Annual 
incidence rates vary from 15 per 1000 among persons aged 75–79 
years to 98 per 1000 among nonagenarians, when the estimates are

years to 98 per 1000 among nonagenarians, when the estimates are 
corrected for dropouts due to death (Fig. 8.3.2; Ref.26). Regardless 
of the aetiology underlying the cognitive deﬁ  cits, the high preva-
lence and incidence highlight the importance of this syndrome in 
the ageing population. Given that the criteria for cognitive impair-ment in non-demented persons are still under construction, and 
that there is no efﬁ  cacious treatment to stop the possible progres-
sion to AD, at the moment we must be cautious with diagnosing MCI, which may cause an unnecessary burden on patients and 
relatives due to the unclear prognosis. However, it is clinically 
relevant to identify all persons with cognitive deﬁ  cits due to treat-
able conditions such as depression, low-level vitamin B
12, and use 
of drugs.
Incidence and risk factors

12, and use 
of drugs.
Dementia incidence is similar in all continents and from different regions of the world (Table 8.3.1). Slightly lower rates detected in US in comparison with those in Europe and Asia are likely to be 
due to differences in study designs and case ascertainment.
(27) AD 
accounts for 60–70 per cent and VaD accounts for 15–20 per cent of all dementia cases. The incidence of both AD and dementia increases almost exponentially with age. However, there are incon-sistent ﬁ  ndings regarding whether the rates continue to increase 
even in more advanced ages. The apparent decline found in some 
studies may be an artifact of the poor response rates, survival 
effects, and nature of populations previously sampled in these very old age groups.
(28)
Age is the strongest risk factor for dementia and AD, suggesting

(28)
Age is the strongest risk factor for dementia and AD, suggesting 
that ageing-related biological processes could be implicated in the 
etiopathogenesis of AD. Further, the strong association with increasing age can be, at least partially, explained by a lifetime 
cumulative risk to different risk factors. Using this approach, the risk of dementia in late life is considered as a result of complex 
Fig. 8.3.2 Corrected age-speciﬁ  c incidence rates with 95 per cent conﬁ  dence intervals of non-dementia cognitive impairment, including th e two mutually exclusive 
deﬁ  nitions of amnestic MCI and CIND. (Reprinted from Alzheimer’s and Dementia, 2, L., Fratiglioni, C. Qui, and K. Palmer, vasc ular cognitive impairment: time for 
prevention?, 202–4, copyright 2006, with permission from Elsevier.)98.4
75.3
14.648.3
020406080100120140
75-79 80-84 85-89 90+
Age groupsIncidence rates per 1000 person-years

1521
Table 8.3 .1 Age-speciﬁ  c prevalence and incidence rates for dementia in the world and different regions: estimated from meta-analyses
Age groups Incidence rate (per 1000 person-years) Prevalence (per 100 population)
Worldwide 
(Gao et al . 
1998)Europe 
(Fratiglioni 
et al . 2000)USA (Jorm and 
Jolley, 1998)East Asia 
(Jorm and Jolley, 
1998)Worldwide 
(Jorm 
et al . 1987)Worldwide 
et al . 1999)Europe (Lobo 
et al . 2000)China (Liu 
et al . 2003)*
60–64 1.1 — — — 0.7 0.9 — 0.3
65–69 3.3 2.4 2.4 3.5 1.4 1.6 0.8 0.770–74 8.4 5.5 5.0 7.1 2.8 3.5 3.0 1.375–79 18.2 16.0 10.5 14.7 5.6 6.9 5.8 2.880–84 33.6 30.5 17.7 32.6 11.1 13.0 12.0 5.685–89 53.3 48.6 27.5 72.1 23.6 25.2 17.4 11.890–95 72.9 70.2 — — — 35.8 28.5 23.795+ 86.8 — — — — 48.1 — —
* The dementia cases in this meta-analysis include only Alzheimer’s disease and vascular dementia.

(Reproduced from Backman, L., Small, B.J. and Fratiglioni, L. Cognitive deﬁ  cits in preclinical Alzheimer’s disease: current kn owledge and future directions. In New frontiers in cognitive aging  
(eds. R.D. Dixon, L. Backman and L.G. Nilsson), pp. 161–77, copyright 2004, with permission from Oxford University Press.)
interactions of genetic susceptibility, biological factors, and envi-ronmental exposures experienced over the lifespan. A summary of 
all these factors is reported in Table 8.3.2, according to different 
biological mechanisms and grade of scientiﬁ  c evidence. As a part 
of an initiative of the Swedish Council on T echnology Assessment 
in Health Care, speciﬁ  c criteria to summarize the scientiﬁ  c evi-
dence concerning risk and protective factors for dementia have been proposed. Similar to criteria adopted for other diseases, these

dence concerning risk and protective factors for dementia have been proposed. Similar to criteria adopted for other diseases, these 
criteria ﬁ  rst integrate the internal validity with basic causal criteria 
to weight the study quality, and then they take into account also number and proportion of the included studies reporting a speciﬁ  c 
association.
(29) Moderate or strong evidence supports several 
genetic, vascular, and psychosocial factors as signiﬁ  cantly related 
to both AD and dementia risk. Whereas implementing preventive strategies targeting the genetic susceptibility is limited, the other 
two hypotheses can easily lead to prevention programmes.
(a) Genetic hypothesis
First-degree relatives of AD patients have a higher lifetime risk of developing AD than the general population or relatives of

First-degree relatives of AD patients have a higher lifetime risk of developing AD than the general population or relatives of 
non-demented subjects. Both genetic and environmental factors contribute to the phenomenon of familial aggregation. Twin stud-ies have shown that heritability of AD is about 58 per cent, whereas other variance may be attributable to non-genetic factors.
(30) The 
APOE ε4 allele is the only established susceptibility gene factor for 
both early- and late-onset AD. The risk effect of APOE ε4 allele 
decreases with increasing age, and after age 75 years, 15–20 per cent of AD cases are attributable to APOE genotype.
(31) Familial aggre-
gation of dementia and AD can be only partially explained by APOE polymorphism, implying that other genetic factors may be active and need to be detected.
(32) Several other genes have been 
examined as possible candidates, but the reports are sporadic or the results are inconsistent.
(33)

(33)
(b) Vascular hypothesis
Whereas the reported association between vascular risk factors and dementia risk is expected, due to vascular dementia, several explanations have been proposed for the association between 
vascular risk factors and Alzheimer-type dementia: (1) coexistence of vascular factors and AD pathology in the elderly; (2) precipitat-ing effect of cerebrovascular disease or interactive effect between Alzheimer-type and vascular lesions in the brain; and (3) misclas-siﬁ cation of mixed dementia as AD. Even if the mechanisms are 
still not fully understood, prevention may be possible as most vascular risk factors and diseases are modiﬁ  able or amenable to

still not fully understood, prevention may be possible as most vascular risk factors and diseases are modiﬁ  able or amenable to 
prevention and treatment. Controlling high blood pressure in mid-dle age, avoiding mid-life obesity, and appropriately treating diabe-tes are the major intervention actions. Some studies also show that people who maintain tight control over their blood glucose levels tend to score better on tests of cognitive function than those with poorly controlled diabetes. Indeed, borderline diabetes or impaired glucose tolerance is also linked to an increased risk of dementia and AD in very old people.
(34) Finally, to postpone clinical expres-
sion of the dementia syndrome in old people, preventing recurrent cerebrovascular disease as well as maintaining sufﬁ  cient cerebral 
perfusion by adequately managing heart failure and avoiding very low blood pressure seems to be critical.
(c) Psychosocial hypothesis

Evidence from both epidemiological and biological studies indi-cates that factors acting at different periods across life course and having an intellectually stimulating nature may contribute in increasing the neural reserve and therefore promote functionally more efﬁ  cient cognitive networks to cope with brain pathology and 
delay the onset of clinical manifestations of dementia. These factors include education, adult-life occupational work complexity as well as late-life social network and intellectually stimulating activities.
(29, 35) Although physical exercise may reduce the risk of

(29, 35) Although physical exercise may reduce the risk of 
brain damage due to atherosclerosis, the relevance of physical activ-ity itself remains in debate, as most physical activities include also social and mental components. Complex leisure activities with physical, mental, and social components seem to have the most beneﬁ  cial effect.
(36) In addition to the reserve hypothesis, other 
mechanisms such as premorbid cognitive ability, vascular damage, 8.3 the ageing population and the epidemiology of mental disorders among the elderly

SECTION 8  the psychiatry of old age 1522
neuroprotection, or detection bias may be possible explanations. 
The most likely effect of a mentally, physically, and socially active life is to postpone the onset of clinical dementia: even delaying dementia onset by 5 years would halve dementia prevalence and substantially decrease the number of dementia cases in the community.
Prevalence and impact
Despite different inclusion criteria, several meta-analyses of prevalence studies have resulted in strikingly similar results (Ref.
27; Table 8.3.1). Currently, more than 24 million people in the 
world have dementia and this number will double in 20 years.(37)
The prognosis of dementia is dramatic. In 3 years, more than

The prognosis of dementia is dramatic. In 3 years, more than 
50 per cent of the dementia cases progress to the severe stage. In the Kungsholmen Project, the proportion of severe dementia among prevalent cases increased from 19 per cent at baseline to 48 per cent after 3 years, and to 78 per cent after 7 years. This progression is due to both cognitive and functional decline. The mean annual rate of cognitive decline as measured with the MMSE varies from –4.0 to –2.0 points. Many predictors of a more rapid cognitive decline have been reported such as initial higher cognitive function, func-tional disability, and brain lesions. The APOE ε4 allele seems not to 
act as relevant prognostic factor.
(38)
Dementia is strongly associated with disability being the major

(38)
Dementia is strongly associated with disability being the major 
determinant of developing dependence and functional decline over 3 years. Approximately half of the persons who developed func-tional dependence in a 3-year period can be attributable to demen-tia.
(39) In industrialized countries, mental disease and cognitive 
impairment are the most prevalent disorders among older adults living in nursing homes or other institutions. However, institution-alization of dementia patients varies depending on age structure, urban or rural residence, and other cultural aspects. In the 75+-year-old population, 70 per cent of incident dementia cases die during the 5 years following the diagnosis, accounting for a mor-tality rate specific for dementia of 2.4 per 100 person-years. Dementia triplicates the risk of death.
(40)Conclusion

Mental disorders are common chronic conditions among the elderly people, and the absolute number of subjects with psychiatric disorders will increase dramatically worldwide in the near future due to the ageing of the populations. In addition, the mental dis-orders have a high impact both at the individual and societal level. Prevention may represent one answer to these challenging conditions. The scientiﬁ  c advances of the last few years have pro-
vided sufﬁ  ciently strong evidence supporting two possible preven-
tative strategies: an active and stimulating lifestyle in late life as well as optimal control of other chronic disease both at middle and late age may decrease the risk of relevant psychiatric disorders such as AD and other dementias.
Hybels, C.F. and Blazer, D.G. (2003). Epidemiology of late-life mental 
Blazer, D.G. and Hybels, C.F. (2005). Origins of depression in later life.

Blazer, D.G. and Hybels, C.F. (2005). Origins of depression in later life. 
Psychological Medicine ,35, 1241–52.
Jorm, A.F. (2001). History of depression as a risk factor for dementia: an 
updated review. The Australian and New Zealand Journal of Psychiatry ,
35, 776–81.
Ferri, C.P ., Prince, M., Brayne, C., et al. (2005). Global prevalence of 
dementia: a Delphi consensus study. Lancet ,366, 2112–17.
Qiu, C., De Ronchi, D., and Fratiglioni, L. (2007). The epidemiology of the 
dementias: an update. Current Opinion in Psychiatry ,20, 380–5.
Fratiglioni, L. and Wang, H.X. (2007). Brain reserve hypothesis in dementia. 
Journal of Alzheimer’s Disease ,12(1): 11–22.
Fratiglioni, L., von Strauss, E. and Qiu, C., (2007). Epidemiology of the 
dementias of old age. In Oxford textbook of old age psychiatry (eds. 
R. Jacoby, T. Dening, A. Thomas, and C. Oppenheimer), pp. 391–406. Oxford University Press, Oxford.

 1. Kinsella, K. and Velkoff, V .A. (2002). The demographics of aging. 
Aging Clinical and Experimental Research ,4, 59–69.Table 8.3 .2 Scientiﬁ  c evidence supporting risk and protective (in italic) factors of dementia and AD by different aetiological hypotheses .
Risk and protective  factors
Vascular Psychosocial Genetic Others
Insufﬁ  cient or limited 
scientiﬁ  c evidenceHigh cholesterol
Cigarette smoking
ObesityLate life high BP
Late life low BP
Heart failure
Silent stroke
Moderate alcohol intakeDietary factors (e.g.  ﬁ  sh and vegetables)Depression
Low SES
Midlife physical activityLate life social networkSeveral susceptibility 
genesHead trauma
Inﬂ  ammatory markers
NSAIDsHRT
Folate and vitamins B12, A, E, and C deﬁ  ciency
Occupational exposure to toxics
Antioxidants
Moderate or strong

NSAIDsHRT
Moderate or strong 
scientiﬁ  c evidenceMidlife high BP
Clinical stroke 
Atherosclerosis 
Antihypertensive drugsLow education
Late life mentally 
stimulating activities
Physical activityAPOE ε4 allele*
Familial aggregation
Abbreviations: AD = Alzheimer’s disease; APOE = apolipoprotein E gene; BP = blood pressure; HRT = hormone replacement therapy; NSAIDs = non-steroidal anti-inﬂ  ammatory drugs; 
SES = socioeconomic status.
(eds. R.D. Dixion, L. Backman and L.G. Nilsson), pp. 161–77, copyright 2004, with permission from Oxford University Press, New York)

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12. Johnson, I. (2000). Alcohol problems in old age: a review of recent 
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16. Bäckman, L., Jones, S., Berger, A.K., et al. (2005). Cognitive impairment 
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environments for explaining Alzheimer disease. Archives of General 
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, 168–74.
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37. Ferri, C.P ., Prince, M., Brayne, C., et al. (2005). Global prevalence of 
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40. Agüero-T orres, H., Fratiglioni, L., Guo, Z., et al. (1999). Mortality

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from dementia in advanced age: a 5-year follow-up study of incident dementia cases. Journal of Clinical Epidemiology ,52, 737–43.8.3 the ageing population and the epidemiology of mental disorders among the elderly

8.4
Assessment of mental 
disorder in older patients
The assessment of older people is not fundamentally different 
from that of younger patients. The principles of taking history and mental-state examination are the same at any age. But if the goals are common, the routes taken to reach them are not necessarily so. For example, an assessment adequate enough to begin treatment of a 30-year-old woman presenting to an outpatient clinic with a depressive illness might take about an hour and involve speaking only to the patient and perhaps brieﬂ  y to her partner, whereas 
the equivalent assessment of an 81-year-old woman in whom uncertainty exists as to whether the diagnosis is that of a depressive or a dementing illness may require more than one interview and necessitate enquiry from several informants. This section will not repeat what can be found in Chapter 1.8.1, but cover only those points which are speciﬁ  c to or need to be emphasized for older 
patients.

patients.
The referral process
Who refers?
Whilst the referral process might be the same as for younger 
patients, it is more often different. In many cases the patient has no idea why, or indeed does not even know or has forgotten that she has been referred. (The feminine gender is used in this chapter because older women are more likely to develop a mental illness and to survive longer than men. However, what is written applies also to men.)
The process has most often been initiated by family members 
who might not have discussed it with the patient. Many old people live alone with no relatives nearby or even in the same country or state, so that referrals are frequently initiated by friends, neigh-bours, or other acquaintances, such as local shopkeepers, social services care workers, and people who run luncheon clubs.
Reasons for referral

In the case of a woman of 30 with a depressive illness, she is referred to a psychiatrist for treatment to effect a remission. However, an older woman of 80 with a similar condition may be referred for a variety of reasons including the following: the primary care doctor might be uncertain of the diagnosis, that is whether it could be dementia; the grown-up children might have removal from home to residential or nursing care as the ﬁ  rst item on their agenda; the patient’s condition may not be the primary issue—there may be 
greater concern for her husband who is failing to cope, perhaps to the extent of physically abusing her.
The informants

A large number of older people seen by psychiatrists are unable to give complete or reliable information about themselves. Frequently, but not invariably, there is a spouse or adult offspring living with the patient. In other cases, however, it is necessary to track down someone less obvious. Neighbours are often helpful at relating recent history, but may know little of past personal or family history. Effort spent in telephoning relatives, even those on the other side of the world, can be invaluable in giving an account of such items as family history or premorbid personality. If an informant is not readily available, for example, because it is night-time in Australia, the psychiatrist should not shelve the task of phoning, but only defer it to the next available opportunity.
Where conﬂ  icting information is given by a variety of informants

Where conﬂ  icting information is given by a variety of informants 
it might be necessary to weigh up the particular ‘hidden agenda’ of 
each one. For example, the husband of a demented woman may 
minimize his wife’s behaviour disturbance for fear that she would be ‘put away’; whereas the daughter may overstate it in order to support a case for her mother’s transfer to a nursing home because her father repeatedly phones her for assistance at all hours of the day and night. Each one of the two informants has cogent reasons for weighting the information, but the psychiatrist and his or her team cannot help to resolve the situation until they understand those reasons.
Professional informants
Psychogeriatrics is as dependent on multi-disciplinary working as any other branch of psychiatry. Many patients seen for the ﬁ  rst

Psychogeriatrics is as dependent on multi-disciplinary working as any other branch of psychiatry. Many patients seen for the ﬁ  rst 
time will already be well known to their primary care doctor who will be able to provide invaluable information. The same frequently applies to community psychiatric nurses who now take referrals directly from general practitioners and may themselves be making referrals to the old-age psychiatry service. The psychogeriatrician can save a great deal of time and effort by consulting community psychiatric nurses and general practitioners before seeing the patient or relatives.

1525
Where to assess the patient
The patient needs to be placed at her maximum advantage to pro-
vide clinical information in whatever setting the assessment takes place. This has to be stated explicitly because the doctor is often required to take active steps to ensure it. Account has to be taken of special sensory impairment. Poor vision may need lights to be switched on so that the patient can see who is asking her questions. Distracting noises will make it even more difﬁ  cult for someone 
with hearing impairment to grasp what is said. Surprisingly often, this may require a request that the television be switched off. Most importantly, examiners need to sit facing the patient with the lips visible, to speak slowly, and to enunciate words carefully. The patient should then be asked if she can hear properly. Simply shout-ing at her is not a substitute for these simple steps.
Social customs vary within and between societies. For instance,

Social customs vary within and between societies. For instance, 
in the United Kingdom and the United States the use of ﬁ  rst names 
is much more acceptable with younger adults than it was 40 years ago. With the current generation of older patients it is not. For them to be called by their ﬁ  rst names unbidden is disrespectful and 
infantilizing. Even if nurses and other non-medical staff do so, doc-tors should not use ﬁ  rst names, unless speciﬁ  cally invited. Instead, 
the surname plus appropriate title (Mr, Mrs, etc.) is correct.
At home
The preferred place to assess older patients is in their own homes, although circumstances sometimes dictate that it will be elsewhere. At home patients feel less intimidated and can be seen within an environment which tells the psychiatrist a great deal that he cannot know in the clinic. If a house is ﬁ  lthy and cold and the patient in a

similar state, and if there is reliable information that this is only a recent phenomenon, then it is a powerful descriptor of the patient’s inability to cope. However, the converse is not always true; a clean and tidy home may only reﬂ  ect someone else’s willingness to 
support and care for the patient who could not otherwise do it herself (e.g. a daughter or neighbour). Another advantage of a home assessment is that cognitive disabilities, such as dyspraxia and agnosia, can be tested in an ecologically valid way (making tea, recognition of family members from photographs) that is more acceptable to a patient than being formally tested with the Mini-
Mental State Examination.
(1)
Assessments at home require more preparation for the doctor

(1)
Assessments at home require more preparation for the doctor 
than is necessary at outpatient clinics where equipment for physi-cal examination and blood tests are available, for example. It is an obvious courtesy to the patient to let her know of the visit before-hand, but it is also wise to arrange for a suitable informant to be present. Furthermore, some older patients are incapable of letting visitors into their houses and the informant might well ﬁ  rst have to 
facilitate the doctor’s access. Elderly patients are much more likely to be suffering from comorbid physical illness which may be the fundamental cause of the mental disorder, for example, pneumo-nia or a urinary tract infection manifesting delirium. The old-age psychiatrist does not therefore need to adhere rigidly to lines of specialty demarcation but rather be aware of the possibility of and prepared to search for physical illness. The basic equipment for a

medical examination, such as a stethoscope, sphygmomanometer, 
and patellar hammer are items to be taken on home visits. Urine testing strips and a thermometer, especially a low-reading thermometer, are also sometimes useful.In a psychiatric hospital

Patients who are assessed after admission to psychiatric beds lack the advantages of being in their own environment, although the opportunity for physical examination is much easier. Another advantage for hospital inpatients is that the assessment can be car-ried out over a longer period of time, since older people tire more easily and cooperation varies from day-to-day. For example, some demented patients will object to undergoing full cognitive assess-ment in one go, especially because they are often aware that they are failing. If a few questions are asked in the course of several short sessions, a more accurate and complete picture of the patient’s abil-ities eventually emerges. If the Mini-Mental State Examination is administered in this way, a higher total can be achieved than if an attempt to administer it all at once meets with sullen refusal after the ﬁ  rst few questions, with all subsequent ones having to be scored 
zero.

zero.
Information from other informants is as crucial for hospital 
inpatients as it is for those seen at home. It is usually the responsi-bility of the house ofﬁ  cer or resident to collect the history, and they 
may be required to telephone several informants in distant and local parts to obtain a full picture which the patient is incapable of providing.
Liaison visits in general hospitals
Liaison visits to patients in general hospitals make up a consider-able part of the old-age psychiatrist’s work because comorbid mental and physical illnesses are very common. In spite of the fact that the host nurse’s instinct is to lead the visiting psychiatrist straightaway to the patient’s bedside, the latter should insist on ﬁ  rst 
reading the case notes (charts) and speaking to the nursing staff who know her best. From the case notes and the prescription cards

reading the case notes (charts) and speaking to the nursing staff who know her best. From the case notes and the prescription cards 
(medication orders) invaluable information on current and past drug therapy as well as details of the patient’s medical history are obtained. Clues as to the patient’s mental state are often best gleaned from the records written by the nurses. Nevertheless, non-psychiatrist doctors, surgeons, and nurses are not accustomed to assessment of the mental state and statements such as ‘confused’ should not be taken at face value, since they stand for anything from slight difﬁ  culty in answering complex questions due to anxi-
ety at being in a strange environment to major mental disturbance. As in most other settings, time spent telephoning informants from the general hospital ward is well invested and may permit the visiting old-age psychiatrist to express an opinion on the patient’s condition more ﬁ  rmly than would otherwise have been possible.

A useful ﬁ  nal step before going to talk to the patient is, if possible, 
to observe her from a suitable distance. In this way signs of delirium, 
disruptive behaviour, social interaction, and other phenomena 
such as dyskinesias may be seen.
When seeing the patient herself, wherever possible she should 
be taken to a separate room and not examined in an open ward where there are other patients. If it is impossible for the patient to leave her bed, then it is usually feasible to move the bed to a more private place.
Nursing and residential homes
Much of that which is required for liaison visits to general hospitals applies to assessment in residential or nursing homes, most notably trying to see the patient in a private room away from  other r esidents. 
Since abuse of elderly people is sometimes an issue in these 8.4 assessment of mental disorder in older patients

SECTION 8  the psychiatry of old age 1526
settings, it is preferable to have at least some time completely alone 
with the patient ﬁ  rst, and if indicated, to check for bruises or other 
injuries, and secondly to allow the patient to tell the doctor things which she might be frightened to do in front of the staff of the home. Another problem in some nursing and residential homes is that the psychiatrist ﬁ  nds that an untrained or unqualiﬁ  ed member 
of staff accompanies him, the quality of whose information may not be at the level of trained nurses. Careful questioning of several members of staff, attention to written records, and telephone calls to appropriate informants should all improve the quality of the assessment.
The history
As has already been made clear, for many older patients a complete history may have to be obtained from a variety of informants. With the patients themselves a more ﬂ  exible approach than is taken with

younger ones is often needed. Whether intellectual failure is obvi-ous and global or there is only relatively mild cognitive impairment (MCI), for some to give a history that is fully chronologically cor-rect can be too great an effort. The examiner must accept these limitations and try to keep the atmosphere as relaxed as possible. Much more than the young, elderly psychiatric patients perceive the psychiatric interview as an ordeal or a form of trial in which it is easy for them to acquire a sense of failure. This in turn induces anxiety and a vicious spiral of ever worsening performance. One way in which the patient can be put at ease is to reassure her that you will come to her main problem in due course but that it would 
be good to hear something of her background ﬁ  rst. For most older

be good to hear something of her background ﬁ  rst. For most older 
patients the family and personal histories are easier to recall than the confusing events which have led up to the referral. This is not simply good for the patient but for the examiner as well. Amongst the most proﬁ  table of pleasures in old-age psychiatry are the life 
stories of people who have lived during some momentous periods of world history. Furthermore, these stories put patients into a context which makes it much easier to understand why and how they have reacted to the mental illness with which they have presented.
As regards the family history speciﬁ  cally, the examiner needs

As regards the family history speciﬁ  cally, the examiner needs 
to be alert to mistakes which could indicate cognitive impairment. A patient may confuse family relationships or misidentify family members quite early in the course of a dementing illness. In other words, inaccurate information from the patient can be as clinically informative as that which is correct. Older patients are not neces-sarily as sophisticated in medical vocabulary as their children and grandchildren. Therefore, to obtain facts about a possible family history of dementia (an important issue), it may be necessary to ask if any blood relative had ‘memory problems’ in late life or ‘had to go into a home’ .
In eliciting the personal history the examiner might need to be 
aware of the historical context at the time in question. Some older patients, however afﬂ  uent they may be now, grew up in poverty or

aware of the historical context at the time in question. Some older patients, however afﬂ  uent they may be now, grew up in poverty or 
other adverse circumstances (e.g. a parent died of tuberculosis dur-ing their childhood) which could still be affecting their psychologi-cal lives. Similarly, education may have been disrupted in a way that is more unusual nowadays. Some patients, notably women, relate how they missed education because they had to look after their younger siblings after mother died or father was killed, because the remaining parent had to go out to work for the family to survive. 
A precise enquiry should be made as to educational attainment, and especially the level of literacy and numeracy which may be the only ‘baseline’ appraisal obtainable for a patient with current dyslexia or dyscalculia.
Whilst it is often very obvious to the examining doctor that a

Whilst it is often very obvious to the examining doctor that a 
patient has cognitive impairment because of her errors and incon-sistencies in giving her personal history, it is very unwise to fore-close on a diagnosis at this stage. Patients with severe depressive illnesses can be even more hesitant than those with, for example, Alzheimer’s disease, or show such retardation and lack of concen-tration on what is being asked that they can portray a clinical picture that is not easily distinguishable from a state of advanced dementia.
Medical and psychiatric history

The nature of the information required is no different from that in younger patients. However, of particular importance in the older population is past and present medication. Drugs taken at the pre-scribed dose, at a wrong dose (due to dementia), or drugs no lon-ger intended to be taken and prescribed sometimes quite a long time ago but of which a residual supply remains, are all potent causes of confusion and even frank delirium in old people. It is therefore good practice to ask to see where all medication is kept and to examine each pack or bottle to check that the amount left is approximately proportionate to that which one might expect given the date the drugs were dispensed. Since elderly people are fre-quently the victims of clinically injudicious polypharmacy, it is common to ﬁ  nd a large quantity of current and prescription-

expired drugs which the patient is taking on a random basis. T o counter this problem proprietary boxes which dispense drugs in 
daily amounts, such as the Dosette or Nomad systems, are used and 
can more easily be checked for compliance or overdosing.
Premorbid personality
Personality is one of the prime determinants of outcome in mental illness at any age, but where older people are concerned too little effort is made, partly for lack of reliable informants, to give a valid assessment of personality. False assumptions are made that some-one has always been awkward or cantankerous, whereas it is shown later that they have become so because of frontal-lobe impairment. Similarly, it is sometimes assumed that a woman has always exhib-ited attention-seeking or manipulative behaviour, when to the surprise of doctors and nurses alike such behaviour disappears following effective treatment for a depressive illness. Every effort

should be made to ﬁ  nd a reliable informant before reaching such 
conclusions.
The mental state examination
Appearance, behaviour, and the environment
A great deal can be learnt from the appearance of the patient and her home environment. Signs of neglect in both are commonly found. A brief tour of the home may reveal rotten food, little or no food, empty bottles of liquor, evidence of poor hygiene or inconti-nence, and inadequate heating. The patient may be dirty and unkempt, and clothes may have been put on in the wrong order (dressing dyspraxia). Particular attention should be paid to rela-tively mild impairment of attention and concentration, since it

1527
might betray a delirium which can be treated to achieve a remark-
able improvement in the patient’s condition. Agitation is another sign to be carefully sought. Sometimes agitation is obvious with behaviour such as pacing and sighing which make it almost impos-sible to communicate with the patient, but at other times it can be allied to psychomotor retardation and perceptible only in tireless movements of the ﬁ  ngers.
Talk
Dysphasia in any of its guises is a frequent manifestation of demen-
tia. Sometimes it is obvious, but not always. For example, it may be difﬁ cult at ﬁ  rst to differentiate between an expressive dysphasia 
(Broca’s dysphasia) and retardation. It is relatively mild or moder-ate receptive dysphasia (Wernicke’s dysphasia), however, which traps the unwary clinician. In such cases the patient may appear to be obtuse, unintelligent, or hard of hearing until it is appreciated that she simply does not understand a considerable proportion of what is said to her.

Even if the patient is not dysphasic, she may be evasive and given 
to circumlocution. Again, this should not be taken automatically as evidence of a premorbid lack of intelligence or pompousness, since it is frequently used as a camouﬂ  age for cognitive impairment. 
A patient with dementia might say ‘Oh of course I know that’ or 
‘I never paid any attention to that sort of thing’ when asked to give an item of current affairs.
In manic or hypomanic illness in old-age slow ﬂ  ight of ideas is 
sometimes missed by inexperienced clinicians or mistaken for evidence of cognitive impairment. Here the normal coherence of thought is disrupted because the patient is distracted from one idea to another, just as in characteristic ﬂ  ight of ideas, but they are deliv-
ered at a normal or even slower pace. The latter can occur if a mixed affective state is present.
Thought content

Much of that which applies to younger patients applies also to older ones and does not need to be mentioned here. However, subtle changes in thought content amounting to a restriction in breadth and a repetitiveness of themes may be noticed. Formal thought disorder which is found in young patients with schizophrenia is extremely rare in the old.
Mood
Depressive illness is commonly missed in older patients. This is partly because the clinical picture can mimic a dementing illness, so that a history from a reliable informant, as has already been stressed, is mandatory. Another reason is so-called masked depres-
sion in which the patient denies depressed mood but presents

sion in which the patient denies depressed mood but presents 
with other symptoms, such as those of apparent physical illness. In this sort of case a reliable account of sleep and appetite distur-bance, weight loss, and anhedonia give clues as to the presence of an affective disorder. It should also be remembered that dementia and depressive illness are common disorders and not infrequently occur together, so that the diagnosis of one does not rule out the other.
Older men are still the group most at risk of suicide in 
most countries of the world where statistics are recorded (see Chapter 4.15.1). The psychiatrist does not shrink from speciﬁ  c 
enquiry about suicidal thinking in patients of any age, but it can sometimes be difﬁ  cult to differentiate between a rational desire to

enquiry about suicidal thinking in patients of any age, but it can sometimes be difﬁ  cult to differentiate between a rational desire to 
die when the time comes and active suicidal ideation. In-depth probing is therefore mandatory and the examiner should not be put off by the patient’s attempts to leave the topic, if he or she thinks that there is likely to be risk of self-harm.
Cognitive examination
In assessing elderly patients more emphasis is usually placed on the cognitive examination than in younger patients. In theory it can be as exhaustive and thorough as assessment by a neuropsychologist, but in the routine practice of old-age psychiatry it usually has to be feasible within the constraints of a consultation which lasts about an hour.
It is in this part of the assessment that the examiner is most

It is in this part of the assessment that the examiner is most 
likely to lose the patient’s cooperation, principally because of the humiliation experienced by some at their own failures. Some patients become angry, indignant, or defensive. Others become anxious and their performance deteriorates. One way to pre-empt this is to preface testing by stressing that this is not a competitive examination and that most people have difﬁ  culty answering some 
of the questions. Correct answers are praised without excessive 
emphasis and incorrect ones are either treated in a neutral way or 
given a positive spin by saying, for example, ‘Well it’s …, but you 
weren’t far off’ .
Many old-age psychiatrists and other members of their multi-
disciplinary team prefer to use standardized questionnaires, such as the Mini-Mental State Examination,
(1) the questionnaire in widest

(1) the questionnaire in widest 
use. It has the advantage that results between and within patients can be compared and progress can be monitored. However, no off-the-shelf test is exhaustive and none produces an adequate cognitive assessment by itself. The clinician therefore needs to have some sort of schema for covering the main areas of cognitive func-tion which would include: memory (in its various aspects) and general information, and naming; the understanding and produc-tion of language; praxis (ideomotor and constructional); sensory recognition (gnosis); abstract reasoning; verbal ﬂ  uency; calcula-

tion; left/right orientation; and executive function (the ability to integrate mental processes for goal-directed activity). The list is not exhaustive and some areas may need to be covered in greater detail as the clinical situation demands. Table 8.4.1 gives a guide to cognitive examination based on an extended Mini-Mental State 
Examination. Clinicians vary in the order and way in which they 
test individual cognitive functions, and the list in Table 8.4.1 is not intended to be prescriptive.
Other aspects of the mental state examination
These do not differ in essence from that in younger adults and are not covered in this section.
Physical assessment
Since physical comorbidity is extremely common, the old-age psy-chiatrist needs to be able and willing to conduct a basic physical examination. In the patient’s home this may not always be easy. 
For instance, it may not be kind to ask a frail person who takes an

For instance, it may not be kind to ask a frail person who takes an 
hour or more to dress and come downstairs in the morning to return to her bed and undress, but it is usually possible to make a reasonable examination of the arterial pulse, blood pressure, and jugular venous pulse, and to auscultate the heart and lungs when 8.4 assessment of mental disorder in older patients

SECTION 8  the psychiatry of old age 1528
the patient is seated. Similarly, a partial neurological examination 
for signs of focal deﬁ  cits is also possible. However, if something 
alerts the doctor to the need to examine an undressed and supine patient, the duty should not be shirked, lest a hitherto unsuspected abdominal mass, or a strangulated hernia are missed.
Patients admitted to psychiatric hospital or nursing home beds 
should all undergo a physical examination. Focal neurological signs may indicate the cause of dementia. Carcinoma of the breast which either dementia or fear has prevented the patient from declaring may be much more treatable than she has believed. All the physical disorders which may be revealed are too numerous to mention, but their detection and treatment nearly always contribute to an improvement in mental function.
Laboratory investigations

Owing to tight budgetary constraints it is sometimes argued that routine laboratory investigations, such as full blood count and chest radiography, are unnecessary for younger adults. Whether or not this is true, with older patients such tests are strongly advised because the treatment of comorbid physical illness improves mental disorder. Furthermore, a treatable or arrestable cause of dementia may be found. For patients with dementia the following 
are recommended: full blood count; serum electrolytes, and creati-nine; liver and thyroid function tests; syphilis serology; vitamin B
12

12
and red cell folate; chest radiography. Medical and nursing staff should also have a low threshold for sending urine for microbio-logical examination (see superimposed delirium below). The vexed question of neuroimaging, an expensive procedure, is much dis-cussed and the debate is not easily summarized or resolved. Most space-occupying lesions can be detected, as can many vascular changes. However, there is nothing pathognomonic for Alzheimer’s disease on CT, magnetic resonance imaging, or single-photon emission tomography. In Alzheimer’s disease, scans may support the diagnosis but not establish it.
General considerations in the assessment of 
older psychiatric patients
Falls
The causes of falls in older people are many and the reader is

Falls
The causes of falls in older people are many and the reader is 
referred to textbooks of geriatric medicine for a full discussion. However, the old-age psychiatrist needs to be aware that many Table 8.4.1  Schema for testing cognitive functions based on an extended mini-mental state examination
Function Subfunction Examples
Orientation Time Year, month, date, day, season
Place Own address or that of hospital, city, county/state, country
Person Own name (married women sometimes cannot give married name); recognize others by name 
or function (e.g. you are a doctor)
Memory Immediate recall Immediate repetition of three objects or a name and (local) address
Delayed recall Repetition as above but after a distractor taskLong-term recall Give historical or personal events (that can be veriﬁ  ed)General information Names of politicians or other VIPs

Concentration Months of the year in reverse order, counting from 20 back to 1; spelling WORLD forwards then 
backwards
Praxis Construction Copy diagram of interlocking pentagons
Ideomotor Draw a clock and set the hands at a speciﬁ  ed time (also a test of executive function)Dressing Put on a jacket; undo, and refasten buttons
Sensory recognition (gnosis) Visual including prosopagnosia Recognize photographs taken from unusual angles and of familiar faces
Auditory Recognize the doorbell
Tactile Recognize objects placed in the palm, e.g. coins
Reading Any sample but use large print, e.g. newspaper headlines
Olfactory Recognize something from the kitchen, e.g. coffee
Language Expressive Repeat ‘no ifs ands or buts’

Understanding Carry out a three-stage commandNaming Naming objects of increasing complexity
Verbal ﬂ  uency List as many items from a category as possible in 1 min, such as boys’ and girls’ forenames, or as 
many words beginning with a speciﬁ  ed letter
Writing Write an ordinary English sentence
Calculation Not too complex—subtraction of serial sevens from 100 is too difﬁ  cult for many. A simple sum 
involving money is better
Left–right orientation Face–hand test (e.g. left hand to left  ear, right hand to left ear); ﬁ  nger recognition on own and 
examiner’s hand
Abstract reasoning ‘In what way are an apple and a banana alike?’
‘In what way are a boat and a car similar?’Interpretation of simple proverbs

Testing one function usually depends on one or more others; for example, most tests depend on understanding of language. Exampl es are neither prescriptive nor exhaustive.

1529
psychotropic drugs precipitate falls through postural hypotension, 
with tricyclic antidepressants and neuroleptics being particular offenders. Neuroleptics induce parkinsonism, putting the patient at risk of tripping against rugs or items of furniture. The clinical implications of falls, especially in older women, are serious because patients are at risk of a fractured neck of femur or (less commonly) a subdural haematoma, both of which carry a high mortality.
Nutrition
Poor nutrition is commonly found in patients presenting to old-age psychiatry services. Even in afﬂ  uent societies many older people are 
amongst the most impoverished or feel that they cannot afford good food. Some are too frail to get out to the shops. Others lack motivation to shop and eat because of depressive illness. Patients suffering from dementia may be incapable of shopping and prepar-ing food. Widowers might never have learned to cook. A vitamin B

12 or folate level at the lower end of the reference range, or even 
below it, is as often a reﬂ  ection of poor nutrition as an indication 
of pernicious anaemia.
Superimposed delirium

Here it is mentioned only that subacute delirium superimposed on another condition is at risk of not being recognized because it is taken to be a manifestation of the underlying illness, usually dementia. This is particularly the case when a subclinical urinary tract infection occurs in a demented patient. It is of clinical rele-vance because treatment of the urinary tract infection results in a great improvement in the patient’s mental state. On routine assessment particular attention should therefore be paid in the his-tory to evidence of sudden worsening of a stable or only slowly deteriorating condition, and to nocturnal disturbance especially with (usually visual) hallucinations. On examination of the patient herself the level of consciousness, awareness of the environment, attention, and concentration should be noted.Delirium is described in Chapter 4.1.1, and special features in 
older people are considered in Chapter 8.5.1.

Reassessment after treatment
Because so much of psychiatry is practised in the community, it is impossible for all patients to be reassessed by a psychiatrist after treatment. In hospital or outpatient clinics it is feasible, but not for the majority of older patients who live at home. Furthermore, in areas where the population is geographically widespread, it is very difﬁ cult if not impossible for many older people, who may be frail 
and inﬁ  rm, to travel long distances to attend clinics. Much of the 
follow-up assessment in old-age psychiatric services is therefore carried out by other members of the multi-disciplinary team, such as psychologists or occupational therapists, but mostly by commu-nity psychiatric nurses. It is essential for the psychiatrist to meet regularly with members of the team seeing patients in the com-munity to discuss the progress of individual patients following treatment.

Goldberg, D. and Murray, R. (eds.) (2006). The Maudsley handbook of 
practical psychiatry  (5th edn). Oxford University Press, Oxford.
Hodges, J.R. (2007). Cognitive assessment for clinicians  (2nd edn).Oxford 
Jacoby, R., Oppenheimer, C., Dening, T. et al. (eds.) (2008). The Oxford 
textbook of old age psychiatry . Chap. 10–12. Oxford University Press, 
Oxford.
 1. Folstein, M.F., Folstein, S.E., and McHugh, P .R. (1975). ‘Mini-mental 
state’ . A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research ,12, 189–98.8.4 assessment of mental disorder in older patients

8.5
Special features of clinical 
syndromes in the elderly
Contents
 8.5.1 Delirium in the elderly
 8.5.1.1 Mild cognitive impairment
 8.5.2 Substance use disorders in older people
 8.5.3 Schizophrenia and paranoid disorders in 
late life
Barton W. Palmer, Gauri N. Savla, and Thomas W. Meeks
 8.5.4 Mood disorders in the elderly
 8.5.5 Stress-related, anxiety, and obsessional disorders in elderly people
 8.5.6 Personality disorders in the elderly
 8.5.7 Suicide and deliberate self-harm in elderly people
 8.5.8 Sex in old age
8.5.1 Delirium in the elderly
Note  Dementia in people of all ages is considered in Part 4, Section

Note  Dementia in people of all ages is considered in Part 4, Section 
4.1, where the following topics are considered: Chapter 4.1.2 Dementia: Alzheimer’s disease; Chapter 4.1.3 Frontotemporal dementias; Chapter 4.1.4 Prion disease; Chapter 4.1.5 Dementia with Lewy bodies; Chapter 4.1.6 Dementia in Parkinson’s disease; 
Chapter 4.1.7 Dementia due to Huntington’s disease; Chapter 4.1.8 Vascular dementia; Chapter 4.1.9 Dementia due to HIV disease; Chapter 4.1.10 The neuropsychiatry of head injury; Chapter 4.1.11 Alcohol-related dementia (alcohol-induced dementia; 
alcohol-related brain damage); Chapter 4.1.13 The management of 
dementia.

dementia.
Although delirium occurs at all ages, it is most frequently encoun-tered in late life. This is because delirium is the result of an interac-tion between individual vulnerability factors (e.g. brain disease, sensory impairment) and external insults (e.g. physical illness, medication), the rates of which both increase with age. Our current concept of delirium derives principally from the ﬂ  orid clinical 
stereotype that has evolved from centuries of clinical observations on younger patients, and it may not be applicable to our histori-cally unique ageing population. In younger adults, a major physical insult is usually necessary to precipitate delirium, which is often a dramatic disturbance. This is not the case in vulnerable elderly patients when relatively mild physical, psychological, or environ-mental upsets may be sufﬁ  cient to bring about acute disturbances

of mental functioning. These disturbances may be less obvious 
than in younger patients, particularly if they occur in the context 
of pre-existing cognitive impairment. Consequently, despite being common and problematic, delirium in elderly patients is frequently missed or misdiagnosed as dementia or depression by medical and nursing staff.
(1) This is unfortunate, because delirium is an impor-
tant non-speciﬁ  c sign of physical illness or intoxication, and if left 
untreated there may be costly consequences, both for the patient and for health services.
The clinical features of delirium are described in Chapter 4.1.1. Most delirium in elderly patients is of the quiet hypoactive variety, lacking the more ﬂ  orid disturbances in mood, perception, and behaviour

that bring the disorder to clinical notice. Reversible cognitive impair-ment in elderly patients is associated with reduced conscious level, poor attention, poor contact with the patient, incoherent speech, reduced psychomotor activity, lack of awareness of surroundings,

1531
poor orientation, and poor memory.(2) Hyperactive delirium does 
occur in elderly patients, but it is less pronounced, with the overac-tivity usually conﬁ  ned to purposeless behaviour such as pulling at 
the bedclothes. Violent behaviour is uncommon; elderly patients are more likely to injure themselves than others.
The ICD-10 and DSM-IV diagnostic criteria for delirium are 
described in Chapter 4.1.1. They are not entirely concordant; ICD-10 is more restrictive, resulting in the diagnosis of fewer cases.
(3) However, the two systems agree on four essential features: 
disturbance of consciousness, disturbance of cognition, rapid onset/fluctuating course, and evidence of an external cause. Unfortunately, none of these features is speciﬁ  c for delirium as 
opposed to dementia, and the current diagnostic criteria are poor predictors of outcome, deﬁ  ned in terms of improvement in cogni-

tive function. Reversibility of cognitive impairment may be the most discriminating feature of delirium,
(2) but is problematic as a 
diagnostic criterion since outcome is unknown at the outset.
Another shortcoming of the current classiﬁ  cations of delirium is 
that they do not recognize the partial and transitory disturbances that are commonly observed in elderly patients. Subsyndromal delirium is common, and is part of a continuum between normality and the full syndrome. Subsyndromal cases are clinically signiﬁ  cant, since they have the same risk factors and the same 
increased mortality as syndromal cases.
(4)
The diagnosis of delirium is a two-stage process: ﬁ  rst, diagnose

(4)
The diagnosis of delirium is a two-stage process: ﬁ  rst, diagnose 
the delirium, and second, identify the underlying cause or causes. The diagnosis of delirium in elderly patients can be problematic, given the predominantly hypoactive clinical picture and the unre-liability of ‘positive’ symptoms. However, it is important to con-sider the possibility if cognitive decline is rapid, and if any of the recognized signs and symptoms are present. A good informant history from relatives or ward staff is essential to establish the onset and course of the disorder. Routine screening procedures may be useful in identifying patients who develop delirium while in hospital. Brief instruments such as the Mini-Mental State Examination
(5) are not diagnostic, but will alert the clinician to

(5) are not diagnostic, but will alert the clinician to 
any sudden decline in cognitive function. More extended diag-nostic instruments are also available, such as the Delirium Rating Scale,
(6) the Confusion Assessment Method,(7) and the Delirium 
Symptom Interview.(8) Another approach to screening for deliri-
um is to identify those at particular risk of developing the disorder. Predictive factors related to the patient include: visual impair-ment, severity of illness, cognitive impairment, and a blood urea nitrogen/creatinine ratio of 18 or more.
(9) Hospital- and treat-
ment-related factors include: use of restraints, malnutrition, use of more than three medications, bladder catheterization, and the number of iatrogenic events.
(10) These factors are multiplicative 
in their effect.
The differential diagnosis of delirium includes most other

The differential diagnosis of delirium includes most other 
psychiatric disorders in this age group. These disorders are them-selves risk factors for delirium, so the possibility of co-morbidity must always be considered. When in doubt, investigate and manage as delirium until the situation is clear.Dementia
Dementia is a major risk factor for delirium, and in practice co-morbidity commonly occurs. However, differential diagnosis is important, as episodes of delirium need to be identiﬁ  ed in order 
for them to be managed effectively. Recent onset and rapid decline of cognitive functioning, from whatever baseline, indicate an episode of delirium until proved otherwise. Delirium in elderly patients can be prolonged, and failure to recover quickly following treatment of the cause does not necessarily indicate an underlying dementia. It is important to have a good history of pre-morbid functioning.

Delirium can be difﬁ  cult to distinguish from severe depression in 
elderly patients, cognitive impairment associated with severe depression is usually relatively mild in comparison with the affec-tive disturbance, whereas the reverse is true of delirium. The pat-tern of diurnal variation also varies in the two disorders, with depressed patients tending to be worse in the mornings, and deliri-ous patients in the evenings. Elderly depressed patients are at 
increased risk of delirium, either through self-neglect or because of the antidepressant treatment they are receiving. Anticholinergic 
tricyclic drugs are particularly troublesome in this respect. Adverse life events, such as bereavement, may precipitate both depression and delirium in vulnerable individuals.
Mania
Mania is much less common than delirium in old age, and is often mistaken for it. There may be a previous history of manic-depressive illness, but a proportion of cases of mania in late life are ﬁ  rst pre-

sentations, usually in association with underlying organic brain disease. Elderly manic patients are often exhausted and dehydrated, and so ‘manic delirium’ is a common presentation.
Anxiety states in elderly patients are unlikely to be mistaken for delirium, unless they are particularly severe. Similarly, paranoid states and schizophrenia rarely lead to diagnostic difﬁ  culty, although 
it should be noted that patients with these disorders are at an increased risk of developing delirium, either through self-neglect, or the effects of neuroleptic and anticholinergic medications. A num-ber of other rare conditions in which cognitive, perceptual, affective, and behavioural disturbances occur, such as amnesic syndromes, epilepsia partialis continua, twilight states, the Charles Bonnet syn-drome, neuroleptic malignant syndrome, and catatonia, may also resemble delirium. If the history and c linical examination are incon-

clusive, EEG may be helpful in maki ng the diagnosis.
The community prevalence of delirium increases with age, rising to 
14 per cent in those aged 85 years and older. In medical and surgi-cal inpatients, the rates of delirium vary considerably (prevalence, 10–30 per cent; incidence, 4–53 per cent), because of methodologi-cal and population differences. Similar rates are also found in stud-ies of acute psychogeriatric admissions.
(11) Some patient groups, 
such as those with hip fractures, have consistently higher rates. Other at-risk populations, such as nursing home residents, have received less systematic investigation, but the available evidence 8.5.1 delirium in the elderly

SECTION 8  the psychiatry of old age 1532
suggests that they also have rates of delirium comparable to those 
found in elderly inpatients.
Aetiology
Almost any physical illness can give rise to delirium in elderly patients. The most common physical causes are listed in Table 8.5.1.1. In many cases the underlying cause is not obvious, and the delirium may be the most prominent presenting feature. The aetiology is commonly multi-factorial, and all contributory factors need to be identiﬁ  ed and treated. As a rule, hyperactive delirium is more commonly due to infection and toxic/withdrawal 
states, whereas hypoactive delirium is more commonly due to metabolic abnormalities.
Drugs are an important cause of delirium in elderly patients, due

Drugs are an important cause of delirium in elderly patients, due 
to age-associated changes in their distribution, metabolism, and excretion. These pharmacokinetic changes are very variable, with the result that toxicity at apparently therapeutic doses is unpredictable. Certain drugs are particularly prone to cause delirium in elderly patients, for example those with anticholinergic activity. Tricyclic antidepressants, thioridazine, and benzhexol are particularly toxic in this respect, but many of the drugs commonly prescribed to elderly patients have some degree of anticholinergic activity, for example, digoxin, prednisolone, cimetidine, ampicillin, and warfarin. Individually, this activity may be small, but the cumulative effect can be signiﬁ  cant if patients are on multiple medications.
(12)
Patients with Alzheimer’s disease are particularly prone to develop

(12)
Patients with Alzheimer’s disease are particularly prone to develop 
delirium when given anticholinergic drugs, perhaps because their central cholinergic function is already impaired. In a minority of particularly vulnerable elderly patients, purely environmental and psychological insults are sufﬁ  cient to cause delirium. The mecha-
nisms of action in these cases are not known, but may involve factors such as sensory deprivation and stress responses via the hypothalamic-pituitary-adrenal axis.
Traditionally, delirium has been regarded as a transient condition that proceeds to either recovery or death. In the majority of cases, the delirium is brief, but about one-third of patients have pro-longed or recurrent episodes.
(13) Delirium is associated with

(13) Delirium is associated with 
increased short-term mortality in elderly patients, mainly because of the severity of the underlying illness. Delirium interferes with the processes of diagnosis, treatment, and rehabilitation, and as a result patients have longer hospital stays and higher rates of func-tional decline and discharge to nursing homes.
(14) Increased length 
of stay and mortality are particularly associated with hypoactive delirium. In general, patients with hyperactive delirium appear to be less severely ill than those with hypoactive delirium; this may be due to differences in the cause of the delirium, or to the fact that hyperactive delirium is more likely to be identiﬁ  ed and the causes 
treated.
Prospective studies have shown that the prognosis, in terms of 
persistent or recurrent symptoms, is relatively poor in elderly patients.
(15) This is probably because those who experience delirium

(15) This is probably because those who experience delirium 
are a vulnerable group who are likely to develop the condition pro-vided there is sufﬁ  cient external insult. A proportion will also be 
suffering from a form of dementia, which will increase the vulnerability to delirium as it progresses. There is evidence that delirium is followed by persistent cognitive decline,
(16) which raises 
the possibility that it (or the underlying cause) is a risk factor for the development or exacerbation of dementia.
Evaluation of treatment
Evidence regarding the efﬁ  cacy of treatments for delirium is sparse

Evidence regarding the efﬁ  cacy of treatments for delirium is sparse 
(Chapter 4.1.1). The cholinergic hypothesis of delirium raises the possibility that cholinergic agonists, such as the cholinesterase inhibitors licensed for the treatment of Alzheimer’s disease, may be of value in the prevention and treatment of delirium.Table  8.5.1.1 Common causes of delirium in elderly patients
Drugs
PsychotropicsHypnoticsAnticonvulsants
Dopamine agonistsAnalgesicsAnaestheticsAlcohol withdrawal
Infection
Urinary tract infectionsPneumoniaSepticaemiaUlcers, pressure sores, gangrene
Endocarditis
Postsurgical wound infection
Metabolic and endocrine
Electrolyte abnormalitiesUncontrolled diabetesHyper/hypothyroidismRenal failureHepatic failure
Hypothermia
Malnutrition
Cardiovascular
Cardiac failureMyocardial infarctionVascular diseaseAnaemia/polycythaemia
Respiratory
Pulmonary embolismPneumothorax
Pleural effusion
Intracranial

TraumaSubdural haematomaStrokeTumourEpilepsy
Gastrointestinal
Perforation
Pancreatitis
Cholecystitis/cholangitisHaemorrhageConstipation

1533
There are four important steps in the management of delirium(17):
Address the underlying causes (see above)
Behavioural control
This aspect of delirium management can be divided into pharma-
cological and non-pharmacological strategies. Non-pharmacological interventions in delirium are aimed at reducing the confusing, frightening, and disorienting aspects of the hospital environment in which most patients ﬁ  nd themselves. They have received little 
formal evaluation, but features such as good lighting, low noise levels, a visible clock, and the reassuring presence of personal pos-sessions and familiar individuals, such as relatives, are thought to be helpful. Any invasive intervention, including personal care tasks, should be introduced and explained simply, slowly, clearly, and repeatedly before it is carried out. Holding the patient’s hand while talking helps to focus attention and provides reassurance.
The drug treatment of the symptoms and behaviours of delirium

The drug treatment of the symptoms and behaviours of delirium 
in the elderly is similar to that of younger patients, although it is necessary to start with lower doses, such as haloperidol 0.5 to 2 mg orally, or intramuscularly if necessary, repeated until the distur-bance is controlled. Prescriptions should be for short periods only (up to 24 h) to encourage review of the effects and the necessary dosage. Once the delirium has resolved, the medication should be reduced/discontinued over a period of 3 to 5 days. If the patient cannot tolerate typical or atypical neuroleptic drugs, then a benzo-diazepine (for instance, diazepam, lorazepam, or alprazolam) should be used instead.
Prevent/treat complications

The complications that befall patients with delirium probably contribute to the adverse outcomes associated with this condition. For example, hyperactive delirium is associated with falls during the hospital admission, whereas hypoactive delirium is associated with the development of pressure sores. Other complications of delirium include urinary incontinence, sleep disturbance, malnutrition, and immobilization; all of these problems should be anticipated and prevented where possible.
Rehabilitation and family support
Given the risk of functional decline following delirium, every effort 
should be made to return the patient to their pre-morbid level of 
functioning. ADL capacity should be assessed regularly, and inde-

pendence encouraged where possible. The patient’s family need to be involved in the rehabilitation process, as they will be largely responsible for aftercare following discharge. They should know that delirium is often recurrent, and be advised about the early signs of this. Indeed, delirium is a useful marker of vulnerability, and of the need for more intensive community aftercare.
The modern hospital environment contributes signiﬁ  cantly to the 
development of delirium in elderly patients, and multi-component interventions to improve poor clinical practice have been shown to reduce cost-effectively the incidence of delirium in elderly inpa-tients.
(18) The following areas are important:◆ Prescribing

Avoid where possible any drugs with known deliriogenic potential, particularly in at-risk individuals such as those with Alzheimer’s disease. There should be regular review of the drug chart, with the aim of keeping the number of drugs to the minimum necessary. Non-pharmacological sleep-promotion strategies should be used in preference to hypnotic drugs.
◆ Ward environment and routines
These should aim to minimize disorientation, sensory impairment, and sleep deprivation. Patient mobility should be encouraged, as should adequate food and ﬂ  uid intake. Medical and nursing staff 
should be trained to recognize and manage delirium.
◆ Surgical routines
Good preoperative, perioperative, and postoperative care (especially with regard to infection control, blood pressure, and oxygenation) will reduce the risk of postoperative delirium.
American Psychiatric Association. (1999). Practice guideline for the

American Psychiatric Association. (1999). Practice guideline for the 
treatment of patients with delirium . American Psychiatric Association, 
British Geriatrics Society. (2006). Guidelines for the prevention, diagnosis and 
management of delirium in older people in hospital .British Geriatrics 
Society, London.
Byrne, E.J. (1994). Confusional states in older people . Edward Arnold, 
London.
Lindesay, J., Rockwood, K., and Macdonald, A. (2002). Delirium in old age .
Lipowski, Z.J. (1990). Delirium: acute confusional states . Oxford University 
1. Bowler, C., Boyle, A., Branford, M., et al. (1994). Detection of psychiatric 
disorders in elderly medical in-patients. Age and Ageing ,
23, 307–11.
2. Treloar, A.J. and Macdonald, A.J.D. (1997). Outcome of delirium: 
Parts 1 and 2. International Journal of Geriatric Psychiatry ,
12, 609–18.

3. Liptzin, B., Levkoff, S.E., Cleary, P .D., et al. (1991). An empirical study of 
diagnostic criteria for delirium. The American Journal of Psychiatry ,148,
451–7.
4. Levkoff, S.E., Liptzin, B., Cleary, P .D., et al. (1996). Subsyndromal 
delirium. The American Journal of Geriatric Psychiatry ,4,
320–9.
5. Folstein, M.F., Folstein, S.E., and McHugh, P .R. (1975). Mini-mental 
state-a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research ,2, 1891–8.
6. Trzepacz, P .T., Baker, R.W., and Greenhouse, J. (1988). A symptom rating 
scale for delirium. Psychiatry Research ,23, 89–97.
7. Inouye, S.K., van Dycke, C.H., Alessi, C.A., et al. (1990). Clarifying 
confusion: the confusion assessment method. Annals of Internal 
Medicine ,113, 941–8.

8. Albert, M.S., Levkoff, S.E., Reilly, C., et al. (1992). The delirium 
symptom interview: an interview for the detection of delirium symptoms in hospitalized patients. Journal of Geriatric Psychiatry 
and Neurology ,5, 14–21.
9. Inouye, S.K., Viscoli, C.M., Horowitz, R.I., et al. (1993). A predictive 
model for delirium in hospitalised elderly medical patients 
based on admission characteristics. Annals of Internal Medicine ,
119, 474–81.8.5.1 delirium in the elderly

SECTION 8  the psychiatry of old age 1534
10. Inouye, S.K. and Charpentier, P .A. (1996). Precipitating factors 
for delirium in hospitalized elderly persons. Predictive model and 
interrelationship with baseline vulnerability. The Journal of the 
American Medical Association ,275, 852–7.
11. Lindesay, J., Rockwood, K., and Rolfson, D. (2002). The epidemiology 
of delirium. In Delirium in old age  (eds. J. Lindesay, K. Rockwood, 
and A. Macdonald), pp. 27–50. Oxford University Press, Oxford.
12. Tune, L., Carr, S., Hoag, E., et al. (1992). Anticholinergic effects 
of drugs commonly prescribed for the elderly: potential means of assessing risk of delirium. The American Journal of Psychiatry ,
149, 1393–4.
13. Rudberg, M.A., Pompei, P ., Foreman, M.D., et al.(1997). The natural 
history of delirium in older hospitalized patients: a syndrome of 
heterogeneity. Age and Ageing ,26, 169–74.
14. Inouye, S.K., Rushing, J.T., Foreman, M.D., et al. (1998). Does delirium

14. Inouye, S.K., Rushing, J.T., Foreman, M.D., et al. (1998). Does delirium 
contribute to poor hospital outcome? A three-site epidemiologic study. Journal of General Internal Medicine ,13, 234–42.
15. Levkoff, S., Evans, D., Liptzin, B., et al. (1992). Delirium, the occurrence 
and persistence of symptoms among elderly hospitalised patients. Archives of Internal Medicine ,152, 334–40.
16. Jackson, J.C., Gordon, S.M., Hart, R.P ., et al. (2004). The association 
between delirium and cognitive decline: a review of the empirical literature. Neuropsychological Review ,14, 87–98.
17. Marcantonio, E. (2002). The management of delirium. In Delirium in 
old age  (eds. J. Lindesay, K. Rockwood, and A. Macdonald), pp. 123–51. 
18. Inouye, S.K., Bogardus, S.T., Charpentier, P .A., et al. (1999).

18. Inouye, S.K., Bogardus, S.T., Charpentier, P .A., et al. (1999). 
A multicomponent intervention to prevent delirium in hospitalized 
older patients. The New England Journal of Medicine ,340, 669–76.
8.5.1.1 Mild cognitive impairment
Within the cognitive functioning continuum from normal ageing 
to dementia three broad states can be distinguished: normal func-tioning for age, clear-cut impairment meeting diagnostic criteria for dementia, and mild cognitive impairment (MCI), which falls below normal but short of dementia in severity (Fig. 8.5.1.1.1). There is active debate over what MCI is, how to deﬁ  ne and classify 
this state, and where to set its borders on the described continuum.
(1)
Some deﬁ  nitions depict MCI as the tail-end of normal cognitive 
ageing whereas in other deﬁ  nitions MCI embodies the early clinical

(1)
ageing whereas in other deﬁ  nitions MCI embodies the early clinical 
manifestation of Alzheimer Disease (AD) and other dementias. In 2003, the key elements of different MCI deﬁ  nitions were inte-
grated into a consensus diagnostic and classiﬁ  cation framework,
(2)
thus establishing some common ground in a ﬁ  eld that is still evolv-
ing. MCI has also been positioned as a potentially important target for early treatment interventions to delay progression to dementia.
Nosologically, MCI is not currently included as a diagnostic entity 
in the Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV-TR)
(3) and the International Classiﬁ  cation of Diseases ,
10th revision.(4) The diagnostic categories of Mild Neurocognitive 
Disorder  (DSM-IV-TR) and Mild Cognitive Disorder  (ICD-10) are

Disorder  (DSM-IV-TR) and Mild Cognitive Disorder  (ICD-10) are 
similar to MCI because they require the presence of cognitive impairment but these categories can only be assigned if a speciﬁ  c 
neurological or general medical condition can be identiﬁ  ed to 
account for the cognitive symptoms. Much of the current condition of MCI does not ﬁ  t as it has no aetiologic speciﬁ  cation. Nevertheless, 
MCI is increasingly a presenting condition in primary and special-ized settings of care. Medical practice guidelines have recognized MCI as a risk state for dementia and recommend careful clinical evaluation and monitoring of individuals with this diagnosis.
(5,6)
Nosology
The current nosological entities within the general MCI framework include a variety of deﬁ  nitions and capture overlapping but not 
identical conditions in the ageing population (Fig. 8.5.1.1.2).

Age-associated memory impairment (AAMI)
AAMI describes healthy individuals over the age of 50 that experience memory decline. Formal diagnostic criteria require complaints of memory loss, performance on objective memory tests falling at least 1 SD below norms for young individuals, and intellectual functioning normal. AAMI cannot be diagnosed if there is a Fig. 8.5.1.1.1 Theoretical continuum from normal ageing to dementia: darker 
shading indicates areas of overlap between adjacent states and increased diagnostic challenge. (Reproduced from R. Petersen et al. Apolipoprotein E status 
as a predictor of the development of Alzheimer’s disease in memory-impaired 
individuals, The Journal of the American Medical Association , 273, 
1274–78, copyright 1995, The American Medical Association.)

Fig. 8.5.1.1.2 MCI nosological entities on the continuum from normal ageing 
to dementia. (Reproduced from H.H. Feldman and C. Jacova, Mild cognitive impairment, The American Journal of Geriatric Psychiatry , 13(8), 645–55, copyright 
2005, American Association of Geriatric Psychiatry, Lippincott Williams & Wilkins.)

1535
neurological, psychiatric, or medical condition that can account for 
the impairment.(7)
Age-associated cognitive decline (AACD)
The AACD category covers impairments in any domain affected by ageing, including learning, memory, attention, thinking, 
language, and visuospatial function. There must be self- or inform ant-
reported cognitive decline over at least 6 months and performance on objective cognitive tests at least 1 SD below age- and education-appropriate norms. The cognitive impairment cannot fulﬁ  l dementia 
criteria and is not accounted for by systemic, neurological, or psychiatric disorders.
Cognitive impairment not dementia (CIND)
CIND includes all individuals that cannot be classiﬁ  ed as cogni-
tively normal or as demented. CIND has been applied both in population- and clinic-based studies.
(8, 9) This diagnostic label is 
assigned by clinical judgement when there is memory and/or cog-nitive impairment insufﬁ  cient to meet DSM criteria for dementia,

assigned by clinical judgement when there is memory and/or cog-nitive impairment insufﬁ  cient to meet DSM criteria for dementia, 
without exclusions related to underlying aetiologies. There are to date no operational criteria for this category. Because of its inclusiveness CIND encompasses a range of aetiologies that must be disentangled to be clinically meaningful.
(8, 9)
Amnestic mild cognitive impairment (aMCI)
This amnestic condition is deﬁ  ned as a clinical disorder that

(8, 9)
This amnestic condition is deﬁ  ned as a clinical disorder that 
describes a transitional state between normal ageing and AD. It is characterized by memory impairment in the context of otherwise preserved abilities. The diagnostic criteria for aMCI require mem-ory complaint preferably corroborated by an informant, objective memory impairment for age and education, largely normal general cognition, essentially intact activities of daily living (ADLs), and the absence of dementia. Objective memory impairment, though not anchored to a speciﬁ  c cut point, is generally ≥1.5 SD below 
appropriate norms.
(10)
Mild cognitive impairment (MCI): international 
working group criteria
The MCI concept has recently been broadened to encompass 
multiple patterns of cognitive impairment including amnestic, non-amnestic, single- or multiple-domain deﬁ  cits.
(2) In this frame-

work the classification of MCI requires multiple steps. First, individuals should be judged as neither normal nor demented. Second, there should be evidence of cognitive decline, supported by self and/or informant reports, impairment on objective cogni-tive tests, or evidence of decline over time on these tests. Third, activities of daily living should be mainly preserved, with the provi-sion that complex ADLs can be minimally impaired.
(2) Like CIND, 
this MCI category recognizes multiple aetiologies underlying impairment, and requires their identiﬁ  cation.
Clinical staging scales
Studies of MCI frequently utilize clinical staging scales both to 
deﬁ ne the inclusion criteria as well as to track outcomes. The Clinical 
Dementia Rating (CDR) scale(11) distinguishes ﬁ  ve stages of demen-

tia severity, with a stage of questionable dementia (CDR 0.5), between the stages of healthy (CDR 0) and mild dementia (CDR 1). CDR 0.5 is most often applied to MCI; however, this stage also can include those with functional impairment who meet dementia cri-
teria. Similarly, the Global Deterioration Scale (GDS),
(12) which dis-
tinguishes seven stages of impairment, overlaps with MCI at stage 2 (normal with a subjective complaint) or stage 3 (subtle deﬁ  cits in 
cognition and occupational/social activities), whereas individuals 
with mild dementia may receive a GDS stage 3 or 4. The mapping of MCI onto these staging scales has not yet been fully reconciled.
Prevalence estimates for MCI will naturally vary according to the deﬁ nition, to age and to the setting. In population-based studies,

Prevalence estimates for MCI will naturally vary according to the deﬁ nition, to age and to the setting. In population-based studies, 
AAMI has been estimated to affect up to 38.4 per cent, and AACD between 21 and 35.2 per cent, of individuals aged 60 or older.
(13)
CIND has been reported to affect between 16.8 and 23.4 per cent of individuals aged 65 or older. The prevalence of aMCI has been much lower, at 3 to 6 per cent in similar age groups.
(13) Within the 
broad MCI classification, the multiple domains and single non-memory domain subtypes have been described as roughly twice as frequent as the amnestic subtype, with multiple domain impairment estimated to affect 16 per cent of individuals.
(14,15)
The prevalence of AACD, aMCI, MCI, and CIND varies with age, with a two- to threefold increase from age 65–74 to >85 in CIND (Fig. 8.5.1.1.3).
(8,16)  The prevalence of MCI and related conditions

(8,16)  The prevalence of MCI and related conditions 
within the referral clinic setting is much higher than population estimates.
(17)
Natural history
(a) Progression rates to dementia
While the rate of progression to dementia is 1 to 2 per cent per year for cognitively normal individuals aged 65 or older, the rates for all MCI entities are systematically higher and quite variable (Fig. 8.5.1.1.4). Whereas AAMI has low progression rates (1 to 3 per cent per year) and is closest to a normal population, for all other categories most studies report rates between 10 and 15 per cent per 
Fig. 8.5.1.1.3 The prevalence of CIND with increasing age reported in the 
Canadian study of health and ageing (CSHA)(8) and the Indianapolis study of 
health and ageing.(16)
8.5.1.1  mild cognitive impairment

SECTION 8  the psychiatry of old age 1536
annum, generally over 5-year periods. A meta-analytic study indi-
cated a mean annual conversion rate of 10.24 per cent, with a range of 2 to 31 per cent. The single most important factor accounting for this heterogeneity was the source of the participants, with sub-jects referred to specialist services, either geriatric or memory/dementia clinics, progressing to dementia at roughly twice the rate found for community volunteers.
(18) In studies of CIND annual 
rates have been 17 per cent for a dementia clinic-referred cohort, 9 per cent for a population-based cohort.
(1,9)
An unresolved question is whether all subjects with MCI eventu-
ally develop dementia. In a highly selected aMCI sample with CDR 0.5 followed over 10 years, all subjects eventually progressed to meet dementia criteria.
(19) This evidence has been proposed to 
support the belief that aMCI represents early-stage AD.(19) Other

support the belief that aMCI represents early-stage AD.(19) Other 
studies with similar length of follow-up have not found as high rates of progression and neuropathologic evidence also suggests more heterogeneity, with up to 50 per cent of subjects with aMCI meeting criteria for AD, and the remainder having varied non-AD abnormalities including vascular lesions, argyrophilic grain disease, 
or other conditions.
(20)
(b) Reversion rates to normal
There are consistently proportions of individuals with MCI that 
will revert back to normal cognitive functioning during follow-up. In population-based studies, this backcrossing has sometimes been particularly high (range 4 to >40 per cent after 1.5 to 5 years).
(1)
In clinic-referred samples, reversion rates for CIND appear to be lower (14 per cent after 2 years).
(9) Reversion may in part be a reﬂ ection of an inherent instability in the MCI condition, particularly

(9) Reversion may in part be a reﬂ ection of an inherent instability in the MCI condition, particularly 
when it is defined exclusively by psychometric cut points.(1)
Reversion appears to be more common when there is no clearly identiﬁ  ed aetiology for MCI.
(9)
(c) Mortality risk
The mortality risk of MCI is near twice the risk of cognitively nor-
mal individuals. The estimated relative risk has been 1.5 for AACD, 1.5–1.9 for CIND, and 1.3–1.7 for aMCI while there has been no increased risk reported for AAMI. There is no clear explanation for this increased mortality risk. It is independent of health condi-tions such as cardiac disease, cerebrovascular disease, diabetes, and malignancies, and it may be related to incipient and eventually full-blown dementia.
(21)
Diagnosis: clinical approach
Overview
Figure 8.5.1.1.5 depicts a ﬂ  ow chart for the clinical diagnosis of 
MCI.(2) The diagnostic process begins with an expressed concern

(21)
Overview
MCI.(2) The diagnostic process begins with an expressed concern 
about cognitive functioning from the patient and/or informant. The assessment then requires a careful history from the patient and informant, as well as the mandatory administration of objective cognitive testing. An evaluation of social function and ADLs, both instrumental and basic, is performed to determine whether there is impairment sufﬁ  cient for a dementia diagnosis. 
A clinical judgement must be made of whether the impairment falls outside of the normal range for age and whether it falls within MCI or dementia. The cognitive proﬁ  le can further be classiﬁ  ed 
into single amnestic, multiple domains, or single non-memory domain. The ﬁ  nal step in the diag nostic process is the determination 
of the aetiology of MCI.
Cognitive assessment

The identiﬁ  cation of MCI requires evidence of impairment on objec-
tive cognitive testing. Generally, a cognitive screening test is needed as a ﬁ  rst step. It should be recognized that the most widely used Mini 
Mental State Examination (MMSE) lacks sensitivity for MCI diag-nosis. In turn, two novel instruments (the Montreal Cognitive Assessment, MoCA, and the DemT ect) have been shown to reliably discriminate MCI from normal ageing.
(22) The effects of age and 
educational achievement on test performance and the consequent risk of misclassiﬁ  cations must be kept in mind in the clinical assess-
ment. Irrespective of the instrument that is chosen, there should be coverage of episodic memory, executive functioning and language, which are the most frequent presenting problems in MCI.

Neuropsychological testing (NPT) can be helpful where a clear-
cut determination of MCI is difﬁ  cult following the initial assess-
ment. NPT provides information on the pattern of impairment, with identiﬁ  cation of the domains affected and reference to stan-
dardized scores. Serial NPT may be particularly useful in deﬁ  ning 
the progression from MCI to mild dementia. The rate of decline on tests of memory, executive functioning and language accelerates during the 3- to 5-year time window before diagnosis of full-blown 
dementia.
(22) NPT also has some predictive utility in addressing 
the risk of progression from MCI to dementia. Deﬁ  cits on tests 
of episodic memory and executive functioning have consistently been found to characterize those with MCI that will develop dementia.

(22)Fig. 8.5.1.1.4 Range of annualized estimates of progression to dementia in 
various MCI groups, reported in Refs.(13,14,18)

1537
Neuropsychiatric symptoms (NPS)
NPS may provide a very useful additional domain for evalua-
tion. An estimated 50 to 70 per cent of subjects with MCI have informant-reported NPS. Symptoms of depression, agitation/
aggression, anxiety, apathy, and irritability, while at a low level of 
intensity, nevertheless each have a frequency of >30 per cent. NPS are associated with greater MCI severity and may be predictive of progression to dementia.
(23) The evaluation of NPS is recommended 
within an MCI assessment.
Aetiology
The determination of aetiology is a ﬁ  nal key step in the assessment 
of MCI. It requires additional laboratory studies as well as consid-eration of neuroimaging results. Within a cohort of individuals with CIND, the most prevalent aetiologic subtypes were pre-AD, vascular cognitive impairment, cognitive impairment with psychi-atric illness, and not otherwise speciﬁ  ed (NOS) (Table 8.5.1.1.1).

These CIND aetiologic subtypes differed in their functional and psychobehavioural proﬁ  les, and in their 2-year prognosis. Pre-AD 
and vascular CIND had the highest rates of progression to demen-tia (~40 per cent), with pre-AD subjects developing exclusively probable AD. Psychiatric CIND and CIND NOS had the highest rates of reversion to normal (20 to 30 per cent). Progression to dementia occurred in all aetiologic subtypes (Table 8.5.1.1.1).
(9)
Biomarkers
There are no widely accepted MCI biomarkers at the present time. Research has focused on neuroimaging with MRI and FDG-PET as well as on tau and β-amyloid (A β) protein levels in cerebrospinal 
ﬂ uid (CSF).
On structural MRI, individuals with MCI may show volume loss in 
the medial temporal lobe (MTL) that may presage AD. The key structures of the MTL include the hippocampus and the entorhinal cortex. MTL structures can be rated on visual scales that may 
Table 8.5.1.1.1  Aetiologic subtypes of CIND and their 2-year

Table 8.5.1.1.1  Aetiologic subtypes of CIND and their 2-year 
progression to AD/dementia
Subtype Prevalence
(% within 
cohort)Dementia at 
2-years (% within 
subtype)AD at 2-years 
(% within 
dementia)
Pre-AD 24.6 40.9 100
Vascular 18.1 40.0 33.3Psychiatric 17.3 25.0 75Non-AD degenerative 2.3 33.3 0Neurological 7.3 25.0 25Medical 3.5 60.0 100Mixed 7.6 33.3 100Not otherwise speciﬁ  ed 19.3 24.2 62.5
(Reproduced from G.Y. Hsiung et al. (2006), Outcomes of cognitively impaired not 
demented at 2 years in the Canadian cohort study of cognitive impairment and related dementias. Dementia and Geriatric Cognitive Disorders,  22(5–6), 413–20, with permission 
from S. Karger A.G, Basel.)Fig. 8.5.1.1.5 Diagnostic ﬂ  ow chart proposed by the International Working Group on MCI. (Reproduced from B. Winblad et al. (2004), Mild cognitive impairment—

beyond controversies, towards a consensus: report of the International Working Group on mild cognitive impairment, Journal of Internal Medicine , 256, 240–6, copyright 
2004, John Wiley & Sons, Inc.)Cognitive complaint
Not normal for age
Not demented
Cognitive decline
Essentially normal functional activities
Mild Cognitive Impairment
Impairment in memory?
Only memory
impairment? YES
YES YES NONOMore than one
domain impaired?
Single
nonmemory
MCIMultidomain
MCI
Non-amnesticMultidomain
MCI
AmnesticAmnestic
MCINO8.5.1.1  mild cognitive impairment

SECTION 8  the psychiatry of old age 1538
reasonably predict AD.(24) MRI-based predictive algorithms may 
be better when MTL measures are combined with measures of lat-
eral temporal lobe or anterior cingulate structures, or with perfor-mance scores on episodic memory.
(24) Both whole brain and MTL 
atrophy rates are greater in MCI subjects that progress to AD than in those who do not.
(25)
The characteristic pattern of AD is to have metabolic reductions 
in temporoparietal and posterior cingulate regions on [18F-]-ﬂ  uoro-
deoxyglucose (FDG) PET. This pattern may be seen in individuals with MCI ahead of full-blown disease. Serial PET may show further metabolic deterioration in these areas as well as abnormali-ties in the ventrolateral prefrontal cortex in subjects who progress to AD.
(1) Recently, PET radioligands that bind to cerebral amyloid 
and potentially to tau proteins have been developed. These include Pittsburgh compound B (PiB) ( N-methyl-[
11C]2-(4 ′-methylamin-

ophenyl)-6-hydroxybenzothiazole) for amyloid and FDDNP (2-(1-[6-[(2-[
18F]ﬂ uoroethyl)(methyl)amino]-2-naphthyl]ethylid
ene)malononitrile) for amyloid and tau. Studies with these ligands have revealed higher than normal retention in subjects with MCI, with a pattern that follows the anatomical distribution of AD pathology.
(26,27)  If longitudinal follow-up conﬁ  rms that these MCI 
cases develop AD, PET with PiB or FDDNP could become a diagnostic test for the early identiﬁ  cation of AD.
(24)
Cerebrospinal ﬂ  uid markers
CSF markers can reﬂ  ect the AD pathogenic process including a 
reduction in A β42 as it aggregates into senile neuritic plaques, as

(24)
reduction in A β42 as it aggregates into senile neuritic plaques, as 
well as an increase in total tau (t-tau) and phospho-tau (p-tau), which signals the hyperphosphorylated state of tau. In MCI, the combination of abnormal A β42, t-tau, and p-tau 181 is associated 
with a 17–20 increased risk of developing AD over 4–6 years. Currently, the utility of these markers is limited by the lack of a standardized assay and the variability in measurements obtained at different laboratories.
(28)
There are no standard therapies for MCI. A clinical management plan is formulated on an individual basis in consideration of the cognitive pattern of MCI and its aetiology. There are two goals for treatment: ﬁ  rst, to alleviate the cognitive symptoms of MCI, and 
second, to attempt to delay the onset of dementia in those at risk.
Symptomatic treatment

A 24-week trial of the cholinesterase inhibitor (ChEI) donepezil did not beneﬁ  t subjects with aMCI on its primary endpoints of delayed 
recall and global impression of change. There were beneﬁ  ts on sec-
ondary measures including the ADAS-cog, neuropsycho logical tests of attention, and patient-rated global function (Patient Global Assessment, PGA).
(29)A longer term trial of donepezil with subjects 
with aMCI (the Alzheimer’s Disease Cooperative Study-Memory Impairment Study, ADCS-MIS) demonstrated benefits on the ADAS-cog, memory and language scores, and global meas ures including the CDR sum of boxes but these were conﬁ  ned to the ﬁ  rst 
18 months of treatment.
(30)
(b) Non-pharmacologic therapies

(30)
Cognitive and lifestyle interventions may help the cognitive and behavioural difﬁ  culties in MCI. An 8-week cognitive intervention programme to improve memory strategies produced beneﬁ  ts on 
tests of delayed recall and face-name association, and on se lf-assessed 
everyday memory function in subjects with aMCI.
(31) A 14-day 
healthy lifestyle programme with memory training, physical condi-tioning, relaxation techniques, and a diet plan, showed beneﬁ  ts 
in subjects with mild self-reported memory complaints. These beneﬁ  ts included improved word ﬂ  uency and metabolic changes 
on FDG-PET in dorsolateral prefrontal cortex.
(32) Therapeutic 
approaches of this type require considerable resources, and conﬁ  r-
mation in randomized controlled trials (RCTs) is needed before large-scale implementation in MCI can be recommended. Nevertheless these approaches hold some promise.
Delaying the onset of AD

A considerable number of long and large trials of ChEIs and non-steroidal anti-inﬂ  ammatory drugs (NSAIDs) have been directed at 
delaying the time to diagnosis of AD in those with aMCI. In the 3-year ADCS-MIS trial, treatment with donepezil did not have an effect on the primary outcome measure of progression to AD after 36 months. An interesting observation in the study was that carri-ers of the apolipoprotein E ε4 allele treated with donepezil had a 
reduced risk of progression to AD at all time points.
(30) Similarly, 
rivastigmine was unsuccessful in delaying the time to diagnosis of AD.
(33) A 4-year trial of the COX-2 inhibitor rofecoxib did 
not show treatment beneﬁ  ts on the primary endpoint of percent-
age of subjects that were diagnosed with AD nor on secondary measures of cognition and global function.
(1) Based on the avail-
able data, the lo ng-term use of ChEIs or NSAIDs in MCI, with the

able data, the lo ng-term use of ChEIs or NSAIDs in MCI, with the 
goal of delaying AD onset, cannot be recommended.
An expanding literature supports the hypothesis that a cognitively, socially, and physically active lifestyle in late life may reduce the risk for AD.
(34) Evidence from RCTs to support this hypothesis is not 
currently available and it is premature to recommend organized interventions. There would be little perceived harm in promoting an engaged lifestyle as part of the management of MCI.
The future of MCI

MCI has been a useful construct to focus attention on the cognitive impairment that is going to increase exponentially within our grey-ing societies. It is recognized that MCI is a risk state for developing AD and other dementias. A natural next step will be to develop criteria to diagnose AD earlier. A proposal of research criteria for the early diagnosis of AD has recently been published.
(24) The diag-
nosis builds on a clinical core of early and signiﬁ  cant episodic 
memory impairment and requires in addition the presence of at least one biological footprint of the disease: medial temporal lobe atrophy on structural MRI, abnormal CSF, or reduced temporopa-rietal glucose metabolism on FDG-PET.
(24) Similar frameworks 
are already in place or will be developed for non-AD dementias. As these frameworks will advance, the concept of MCI will likely be signiﬁ  cantly reﬁ  ned and could look quite different by the next 
edition of this textbook.

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socially integrated lifestyle in late life might protect against dementia. 
Lancet Neurology ,3, 343–53.8.5.1.1  mild cognitive impairment

SECTION 8  the psychiatry of old age 1540
8.5.2 Substance use 
disorders in older people
This chapter is divided into three main sections, focussing respec-
tively on alcohol use disorders (AUDs), medication use disorders (MUDs), and use of illegal substances and nicotine, in older people. In each section we focus in detail on deﬁ  nitions and diagnosis, 
epidemiology, aetiology, clinical features, investigations, screening, management, and prognosis. More is known about AUDs in older people, hence this section is the longest, but MUDs in older people is also a signiﬁ  cant problem and abuse of illegal drugs may become 
increasingly important in future years.
Alcohol use disorders (AUDs) in 
older people
The ageing of populations worldwide means that the already signiﬁ  -

cant problem of alcohol use disorders (AUDs) in older people is likely to become even more important in future years. However, AUDs in older people are neglected and underdiagnosed, for the reasons outlined in Table 8.5.2.1, and unless these factors are tack-led proactively there exists a real danger of AUDs in older people becoming a silent epidemic, with negative impacts on all aspects of health and well-being
(1) (see Table 8.5.2.2).
Deﬁ nitions and diagnosis
AUD is a general and broad term, used to include a wide range of 
alcohol-related problems, as outlined in Table 8.5.2.3. Alcohol status may also change throughout life, with one-third of older people with AUDs developing such problems for the ﬁ  rst time in

alcohol-related problems, as outlined in Table 8.5.2.3. Alcohol status may also change throughout life, with one-third of older people with AUDs developing such problems for the ﬁ  rst time in 
later life (late-onset AUDs). A more severe course of AUD, higher levels of antisocial personality and stronger family histories of AUDs are seen in those with early-onset AUDs.
Because of the effects of physical and cognitive ageing, pharma-
cokinetic changes, the increased prevalence of comorbid illness, and interactions with prescribed medication, older people are likely to encounter AUDs at levels of intake lower than the general population. Therefore, the recommended levels of intake for the general population (i.e. up to 21 and 14 units per week for men and women, respectively
(2)) may be inappropriately high for older peo ple. 
However, apart from the NIAAA recommendations of no more than one drink per day for older people,
(3) there is a lack of guid-

ance on safe levels of alcohol intake, and the pursuit of obvious and ‘down and out’ drinkers may lead to a signiﬁ  cant amount of more 
subtle and clinically ‘silent’ AUDs being missed.
Furthermore, the diagnostic criteria used by ICD-10 and DSM-
IV used to describe harmful use and alcohol dependence syndrome may not be applicable to older people, as evidence of diagnostic criteria such as craving, compulsion, tolerance, and withdrawal features may be less clear-cut and masked by other medical condi-tions, and older people may be less likely to encounter the ﬁ  nancial, 
occupational, family and legal consequences of AUDs (see also Table 8.5.2.1 and section on screening).Epidemiology

The prevalence of AUDs in older people varies depending on the screening and diagnostic criteria used, clinical and socio-demographic characteristics (men having levels 4–6 times higher than women) and the level of severity of AUD being deﬁ  ned. In community-based 
studies, for example, 2–4 per cent of older people have been estimated to have alcohol misuse or dependence,
(4) with higher rates of 
16 per cent (men) and 2 per cent (women) when looser criteria such as excessive alcohol consumption are used.
(5) Clinical populations of 
older people have higher levels of AUDs, with emergency department, nursing home and psychiatric inpatients being described as having levels of 14, 18, and 23 per cent, respectively.
(6–8)
The true prevalence of AUDs in older people is often underesti-

(6–8)
mated, for the reasons outlined in Table 8.5.2.1. It is likely, however, that the actual levels of alcohol consumption and AUDs do decline with age.
(9,10)  This decline may be due to factors such as premature 
death of those with AUDs, reduced physiological reserve and comorbid medical illness leading to reduced alcohol intake, age-cohort effects and age-related changes in social networks, occupa-tional, and ﬁ  nancial status.
Aetiology, risk factors, and associations
These factors can be broadly described as being biological/medical, 
social, and psychological in nature. Genetic factors are likely to be important in relation to both early-onset
(11) and late-onset AUDs.(12)
The genetic risk for AUDs may also overlap with risk for other mental disorders such as antisocial personality disorder, other drug use problems, anxiety disorders, and mood disorders.
(13) AUDs

(13) AUDs 
may have a cause and effect relationship with medical illness.
Important social aetiological factors are likely to include male 
gender, bereavement, age-cohort effects, culture and ethnicity, religion, and marital status (higher levels of AUDs in divorced and single). Some social factors, such as marital problems, may have a two-way relationship with AUDs.Table 8.5.2.1  Reasons for the neglect and underdiagnosis of AUDs 
in older people
Patient factors
Older people may be less likely to volunteer information on alcohol intake/AUDs
Recall of alcohol intake may be inaccurate due to cognitive impairmentFeatures of AUDs may be atypical or masked (e.g. presenting as falls, 
 confusion)
Pharmacokinetic changes, comorbid illness, and drug-interactions mean

confusion)
Pharmacokinetic changes, comorbid illness, and drug-interactions mean 
 alcohol-related problems may arise even at relatively low levels of intake
Health service factors
Health care professionals less likely to ask older people about alcohol intake 
 and AUDs
Health care professionals less likely to refer older people for treatment, even 
 when AUD detected
Inappropriate screening and diagnostic tools usedTherapeutic pessimism in treating older peopleInappropriately high levels for ‘recommended’ or ‘healthy’ levels of intake
Family and societal factors
Family members may be less likely to perceive AUD as a problem in older 
 relatives
Ageist attitudes lead to risk of AUDs in older people being perceived as 
 ‘understandable’
AUDs in older people less ‘noisy’, with less impact on absenteeism, antisocial 
 behaviour, crime

1541
Relevant personality factors include the stronger association 
between antisocial personality, hyperactivity, and impulsivity in ‘early-onset’ compared to late-onset AUDs, who may have higher levels of ‘neuroticism’ and depression.
(14)
AUDs in older people, as in all populations, may also have a two-
way relationship with psychiatric disorders such as depression and anxiety disorders. For example, an older person may begin drinking in an effort to self-medicate depressive symptoms, or they may 
become depressed because of their drinking.
(15)
Clinical features and comorbidity
AUDs in older people are linked to signiﬁ  cant morbidity and mor-
tality, affecting practically all aspects of physical, neuropsychiatric and social health and well-being,
(1,16) as summarized in 
Table 8.5.2.2.
Pharmacokinetic changes (reduced physiological reserve, 
reduced metabolic efﬁ  ciency, and increased volume of distribution

reduced metabolic efﬁ  ciency, and increased volume of distribution 
due to a higher fat to lean muscle ratio, leading in turn to relatively higher blood alcohol concentrations in older people) along with the general effects of physical and cognitive ageing, increasing frailty, reduced functional ability, and higher levels of concomitant prescription drug use means that alcohol is relatively more toxic to older people than younger people. Furthermore, as outlined earlier, such toxic effects may be subtle and may be missed or mistaken for other conditions.
AUDs in older people are associated with a wide range of mental 
disorders, such as depression, psychosis, withdrawal syndromes, cognitive impairment, and dementia
(17) (see Table 8.5.2.2) and 
are also associated with an increased risk of suicide.(18) The rela-
tionship between alcohol use and brain damage and dementia is complex,

(19) in that AUDs may increase the risk for different types 
of dementia(20) and there also exist diagnostic entities known 
as ‘amnesic syndrome associated with alcohol use’ (ICD-10) or ‘alcohol-induced persisting dementia’ (DSM-IV). In contrast, light to moderate alcohol use may protect against dementia.
(21)

(21)
The assessment of AUDs in older people begins with a thorough clinical interview and history of alcohol use (quantity and frequency of drinking, beverage type, drinking context), mental state exami-nation, physical examination and collateral history if available, and with the patient’s consent. If indicated by the initial history, additional questions should be asked about features of alcohol dependence syndrome, as they relate to the patient’s physical and psychosocial health. Questions should be framed in a sensitive and non-judgemental way, as patients may disengage and be lost to treatment and follow-up if they feel threatened by the assessment procedure.
(b) Further investigations in AUDs

Following a detailed history and examination, other investigations may be indicated and should be directed by the patient’s clinical status. These may include: blood tests to check the following: urea and electrolytes; full blood count; liver function tests; vitamin B12 and folate levels; neuroimaging (CT or MRI brain); gastrointestinal investigations such as ultrasound, CT, or MRI examinations of the abdomen, upper gastrointestinal endoscopy, and liver biopsy; basic cardiovascular investigations such as electrocardiogram and other Table 8.5.2.2  Physical, neuropsychiatric, and socio-demographic 
aspects of AUDs in older people
1. Physical factors
Hepatic problems: elevated liver enzymes; fatty liver; alcoholic hepatitis; 
 cirrhosis; malignancy
Gastritis, peptic ulcer disease, and bleedingOesophageal varicesAcute and chronic pancreatitis
Malignancies
Mouth, pharynx, larynx, oesophagus, hepatic, colorectal, pancreatic

Ischaemic heart diseaseHypertensionAlcohol-induced arrhythmiasCongestive heart failureAlcoholic cardiomyopathy
Haematological
Macrocytosis (acute effect of alcohol intake and due to vitamin B12 and 
 folate deﬁ  ciency in chronic AUD)
Anaemia (due to gastrointestinal problems)
Musculoskeletal
Falls and fracturesReduced bone densityMyopathy
Metabolic
Hypoglycaemia
HyperuricaemiaElevated lipidsDiabetes more difﬁ  cult to control
2. Neuropsychiatric factors
Cognitive impairment and dementiaFrontal lobe impairmentWernicke–Korsakoff syndromeCerebellar cortical degenerationCentral pontine myelinosisMarchiafava–Bignami diseaseDepression
Psychosis
IntoxicationWithdrawal syndrome (may be more difﬁ  cult to treat in older people)Suicide
3. Socio-demographic

Psychosis
Male genderDivorced, widowed, and single statusSocial isolationUpper and lower ends of socio-economic spectrum
4. Other
Alcohol–drug interactionsAspiration pneumoniaRoad trafﬁ  c and other accidentsTable 8.5.2.3  Types/levels of severity of AUDs
◆ Excessive alcohol consumption (i.e. drinking above recommended levels)
◆ Binge drinking (i.e. episodic bouts of excessive alcohol intake)
◆ Problem drinkers/harmful use/abuse
◆ Alcohol dependence syndrome
◆ ‘Early-onset’ versus ‘late-onset’8.5.2 substance use disorders in older people

SECTION 8  the psychiatry of old age 1542
more detailed investigations if indicated, e.g. echocardiogram and 
24 h blood pressure monitoring.
(c) Screening for AUDs in older people
Screening programmes should aim to detect both clear-cut and subtle cases of AUDs in older people. It must be remembered that screening tests are not diagnostic in themselves, but positive results should lead on to further investigations. Screening methods may be based on self-report alcohol screening instruments such as the CAGE,
(22) the AUDIT,(23) and biophysical measures such as 
blood tests checking mean corpuscular volume and liver function tests.
A systematic review of self-report alcohol screening instruments 
(24) revealed that the CAGE was the most widely 
studied, but that sensitivity and speciﬁ  city varied depending on the

studied, but that sensitivity and speciﬁ  city varied depending on the 
clinical characteristics of the population in question. However, the CAGE is the most well recognized alcohol screening instrument and is quickly and easily administered, so the authors would recommend use of at least this instrument, along with further investigations and assessment scales if problems are detected.
The utility of biophysical screening measures such as carbohy-
drate-deﬁ  cient transferrin, liver function tests or the mean corpus-
cular volume may be less reliable in older people,
(25) because of 
higher levels of comorbid physical illnesses leading in themselves to false-positive and abnormal results. However, they may prove useful when combined with other clinical information, both in the detection of AUDs and monitoring of progress through treatment.
Management and prevention

Primary prevention  strategies should focus on individual older 
people (especially considering that one-third of older people have late-onset AUDs) and can also be directed at the entire population, targeting factors such as ease of access to alcohol, restrictions on alcohol advertising, and education about the adverse effects of drinking. Such primary prevention and public health initiatives tend to be directed towards younger individuals, but they should also take into account the more clinically ‘silent’ AUDs that may develop in older people.
(26)
Secondary prevention  strategies should focus on older people 
who already have ‘at-risk’ drinking, either currently or in the past, and who are at risk of developing worsening problems in the context of diverse factors such as bereavement, social isolation, adjustment to retirement, and physical or psychiatric health problems.
Tertiar y pre vention  involves treatment of existing AUDs.

Tertiar y pre vention  involves treatment of existing AUDs. 
Treatment modalities can be divided into biological/medical, social, and psychological. Biological/medical treatments are most important in the acute setting, where detoxiﬁ  cation may be 
required.
Care should be taken with benzodiazepine-assisted withdrawal 
in older people, in view of the elevated risk of oversedation, confusion, and falls. There are no elderly-speciﬁ  c guidelines on 
benzodiazepine-assisted alcohol withdrawal in older people. 
Lorazepam has been identiﬁ  ed in one review
(27) as the safest choice 
of benzodiazepine for treatment of alcohol withdrawal in older people, in view of the fact that advancing age and liver disease have little impact on its metabolism, and absorption by the intramuscu-lar route is predictable. In practice, however, it is likely that there is more clinical experience with use of long-acting benzodiazepines such as chlordiazepoxide. The choice of benzodiazepine used

should be based on individual patient characteristics such as previ-ous treatments, current medical status (e.g. degree of hepatic impairment) and an objective measure of withdrawal may help guide the dosing regimen (see Table 8.5.2.4).
Parenteral or oral thiamine should be given to prevent develop-
ment of the Wernicke–Korsakoff syndrome. A recent review has concluded that, in the emergency department setting, oral thiamine administration is as effective as parenteral admin-istration.
(28) Again, however, there are no elderly-speciﬁ  c guide-
lines, and individual patient characteristics must be taken into account, such as general health, ability to take oral medication, and compliance.
The three medications that are approved by the US Food and 
Drug Administration to promote abstinence and reduce relapse are Disulﬁ  ram, Acamprosate, and Naltrexone.
(29) However, the limited 
efﬁ cacy of Disulﬁ  ram, combined with the potential for a more

efﬁ cacy of Disulﬁ  ram, combined with the potential for a more 
severe side-effect proﬁ  le means it is best avoided in this age group. 
In contrast, Naltrexone and Acamprosate have been suggested as suitable agents for use in older people.
(30)
Psychosocial aspects of treatment should also be explored. This 
may include addressing social circumstances that may be con-tributing to the AUD (e.g. personal ﬁ  nances and housing). There is 
a dearth of evidence on psychotherapeutic approaches to AUDs in older people, but there is some evidence that older people may respond better to psychotherapy in same-age settings,
(31,32)
and consideration should also be given to support groups such as Alcoholics Anonymous.
Prognosis
The available literature on the topic suggests that older people are at least as likely, if not more likely, to beneﬁ  t from treatment

Prognosis
The available literature on the topic suggests that older people are at least as likely, if not more likely, to beneﬁ  t from treatment 
of AUDs as younger people.
(33,34) However, prognosis in older 
people is likely to vary widely depending on a number of factors relating to the individual themselves and the nature of their AUD, the presence of family and other support systems and the availability of treatment services, particularly services that are tailored to older people.
Table 8.5.2.4  The Clinical Institute Withdrawal Assessment for 
Alcohol-Revised Version (CIWA-Ar) (Reproduced from The South London and Maudsley NHS Trust Prescribing Guidelines, 2005–2006, 
copyright South London and Mandsley NHS Foundation Trust)
 1. Nausea and vomiting
 2. Tremor 3. Paroxysmal sweats 4. Anxiety 5. Agitation 6. Tactile disturbances 7. Auditory disturbances 8. Visual disturbances
 9. Headaches and fullness in head
10. Orientation and clouding of sensorium

9. Headaches and fullness in head
Severity of alcohol withdrawal
Mild: <10Moderate: 10–20Severe: 20+
(Items 1–9 are scored from 0–7 and item 10 from 0–4. Maximum possible score is 67)

1543
Medication use disorders (MUDs) in 
High levels of prescribing of all types of medications for older 
people, which may at times be inappropriate, along with factors such as variable compliance, altered pharmacokinetics, reduced functional ability, and increased levels of physical, psychiatric, and cognitive morbidity mean that older people are at higher risk of developing MUDs than any other age group.
(35) As with AUDs, 
clinical features of MUDs may be atypical and masked by other conditions and thus go undetected and untreated.
(36)
As with AUDs, older people are affected by a wide range of types 
and severity of MUD.
The ICD-10 uses the same general principles of intoxication, 
harmful use, dependence, and withdrawal state that apply to alcohol for use of sedative and hypnotic medications. As with AUDs, elderly-speciﬁ  c criteria are not cited, but the same general

harmful use, dependence, and withdrawal state that apply to alcohol for use of sedative and hypnotic medications. As with AUDs, elderly-speciﬁ  c criteria are not cited, but the same general 
principles apply: older people are likely to experience harm at lower levels of use and clinical features guiding diagnosis are more likely to be atypical and masked by other health problems.
Iatrogenic factors are also important, as drugs may be inade-
quately or underused for treating or preventing conditions, or drugs may be overused, leading to unnecessary exposure of the older individual to adverse effects.
(36)
Older people comprise 13 per cent of the US population, but they have been estimated to use more than 30 per cent of prescrip-tion
(37, 38) and 35 per cent of OTC drugs:(37) it has been estimated

(37, 38) and 35 per cent of OTC drugs:(37) it has been estimated 
that older people use prescription and OTC medications approxi-mately three times as much as the general population. Furthermore, we know that the risk of MUDs increases with polypharmacy, which is common in older people.
(39,40)
Benzodiazepines are the most commonly prescribed psychotro-
pic drugs in older people, with one study of community-dwelling older people in Ireland demonstrating that 17 per cent of partici-pants were prescribed benzodiazepines, with use in females being twice that in males, and 18 per cent of benzodiazepine users taking at least one other psychotropic drug. Furthermore, 52 per cent of benzodiazepine users were prescribed a long-acting benzodiaze-pine.
(41) It has also been reported that depression in older commu-

nity-dwelling people is more likely to be detected if accompanied by anxiety symptoms, and such individuals are at risk of inappro-priate treatment with benzodiazepines.
(42)
Use of opiate analgesia is common in older people and is liable to 
give rise to MUDs. Therefore, use of these medications should be carefully monitored, with due consideration of dose and careful tapering.
(43)
The general principles for aetiology, risk factors, and associations for substance misuse outlined above (see Table 8.5.2.5) also apply to MUDs. Further MUD-speciﬁ  c factors are outlined below in 
Table 8.5.2.6.Clinical features and comorbidity

Clinical features and comorbidities associated with MUDs in older people will vary widely depending on the drug being used and patient characteristics such as age, gender, and presence of other physical and neuropsychiatric problems. An outline of clinical features and comorbidities are listed in Table 8.5.2.7.
As with AUDs, a standard clinical assessment involving a history, mental state, and physical examinations and collateral history will form the basis of an MUD assessment. A list of all prescribed and over the counter medications being used, along with their indications for use, should be recorded. Ideally, the patient should be asked to bring with them all medications in their containers, as this will also give an indication as to levels of adherence or compli-ance. Any reported adverse effects should be recorded, along with 
Table 8.5.2.6  Aetiology, risk factors, and associations of MUDs in 

Biological/medical factors
Genetic predispositionChronic medical conditions (e.g. pain)Age-related pharmacokinetic changesInteractions: other medications and alcoholType of medication (e.g. benodiazepines, analgesics)
Psychosocial factors
DepressionAnxiety disordersPersonality disorderOlder ageFemale genderLower educational levelSeparated or divorced statusTable 8.5.2.5  Risk factors for substance abuse in the elderly 
(Reproduced from R.M. Atkinson (2002), Substance abuse in the elderly, In Psychiatry in the elderly  (3rd edn.) (eds. R. Jacoby and 
C. Oppenheimer), copyright 2002, with permission from Oxford 
University Press).
Predisposing factors
Family history (alcohol)Previous substance abusePrevious pattern of substance consumption (individual and cohort effects)Personality traits (sedative–hypnotics, anxiolytics)
Factors that may increase substance exposure and consumption level

Gender (men-alcohol, illicit drugs; women-sedative–hypnotics, anxiolytics)
Chronic illness associated with pain (opioid analgesics), insomnia (hypnotic 
drugs), or anxiety (anxiolytic)
Long-term prescribing (sedative–hypnotics, anxiolytics)Caregiver overuse of ‘as needed’, medication (institutionalized elderly)Life stress, loss, social isolationNegative affects (depression, grief, demoralization, anger) (alcohol)Family collusion and drinking partners (alcohol)Discretionary time, money (alcohol)
Factors that may increase the effects and abuse potential of substances
Age-associated drug sensitivity (pharmacokinetic, pharmacodynamic factors)Chronic medical illnessesOther medications (alcohol–drug, drug–drug interactions)8.5.2 substance use disorders in older people

SECTION 8  the psychiatry of old age 1544
symptoms and signs indicating underuse, overuse, or intermittent 
use of medication.
(b) Investigations in MUDs
Blood levels of the patient on some prescribed medications may be checked in order to assess levels of compliance and to establish if the blood level is within the therapeutic window for the drug in question (e.g. lithium, carbamazepine). Other biophysical measures may also be indicated that provide proxy measures of medication compliance, such as random or fasting glucose levels and levels of glycosylated haemoglobin, to assess for level of diabetes control and compliance with hypoglycaemic agents or insulin.
(c) Screening
There are no routinely used screening measures for MUDs in older people. However, use of a measure such as Beers’ criteria
(44,45) may 
be a useful addition to the overall assessment of an older person if an MUD is suspected.
(a) Primary and secondary prevention

Along with patients themselves, health care workers, family members, and carers all have important roles in the primary and secondary prevention of MUDs in older people. Prescriptions should be reviewed regularly with a view to simpliﬁ  cation and 
rationalization if possible, and the practice of giving ‘repeat prescriptions’ without clinical assessment should be discouraged.
Community pharmacists have an important role in providing 
education and advice on the use of both prescription and over the counter medications.
As older people may have physical and cognitive disabilities that 
interfere with appropriate use of medication,
(46) devices such as 
dosette boxes and combination packs may be helpful.(47,48)
Secondary prevention of MUDs in older people should focus on those with a past history of MUD.

(b) Tertiary prevention
T ertiary prevention of MUDs in older people will depend on the medication in question and the clinical and socio-demographic proﬁ le of the patient. Admission to a medical or psychiatric ward 
may be required to facilitate reduction or stopping of certain medications, e.g. benzodiazepine detoxification, as outpatient detoxiﬁ  cation in older people may be hazardous.Prognosis in MUDs
Similar prognostic indicators that apply to AUDs are likely to be 
relevant to MUDs, and centre on the individual’s clinical and socio-demographic characteristics, levels of support, and available services. The duration of abuse and the medication or medications being abused is also of relevance.
Illicit drug use and nicotine use in 

Illicit drug use in older people is far less of a problem in compari-
son to AUDs and MUDs. Lifetime prevalence rates for illicit drug dependence have been estimated as 17 per cent for 18–29 year olds, 4 per cent for 30–59 year olds, and less than 1 per cent for those over the age of 60.
(49) Epidemiological Catchment Area data sug-
gest a lifetime prevalence rate for illegal drug use of only 1.6 per cent for older people.
(50)
Several other sources of data suggest similarly low rates of illegal 
drug use among older people. However, the ageing of the ‘Baby-boomer’ generation is likely to result in a cohort of older people who are healthier and have higher life expectancies than previous generations of older people, but who also carry with them higher rates of illegal drug use.
(51)
Principles similar to those seen with AUDs and MUDs apply, in

(51)
Principles similar to those seen with AUDs and MUDs apply, in 
that lower levels of drug intake are required to cause harm and pre-sentation may be atypical and thus go undetected. There is a dearth of evidence in the literature on detoxiﬁ  cation and opiate replace-
ment therapies in older populations.
Nicotine use (primarily through cigarette smoking) in older peo-
ple arguably causes more signiﬁ  cant morbidity and mortality than 
AUDs and MUDs, but the problem tends not to be addressed by psychiatrists, because of a lack of signiﬁ  cant neuropsychiatric 
effects of nicotine use, and a more obvious impact on many aspects of physical health. As with AUDs and MUDs, smoking in older people is treatable, and any comprehensive approach to improving the health of older people, at the individual clinical level or public health level, should involve education about the adverse effects of 
smoking and efforts at active treatment through the use of nicotine 
replacement therapies

(52) or antidepressants such as nortriptyline 
or buproprion.(53) However, an important and circular relation-
ship has been described between depression, smoking, and medical illness that complicates smoking cessation in those who have a his-tory of depression.
(54)
In this chapter we have highlighted the importance of AUDs and MUDs in older people, in terms of their prevalence and their important but often underrecognized contribution to morbidity and mortality. AUDs are underdetected, misdiagnosed, and often completely missed in older populations. However, despite ageist and therapeutically pessimistic assumptions, AUDs in older people are as amenable to treatment as in younger people, and treating an AUD in an individual of any age can lead to signiﬁ  cant beneﬁ  ts in 
their quality of life.
Likewise, the wide variety of MUDs in older people may be asso-

ciated with addiction to medication and the undertreatment and inappropriate treatment of medical and psychiatric conditions. Considering that older people are the highest consumers of Table 8.5.2.7  Clinical features and comorbidity associated with 
MUDs in older people
Neuropsychiatric (all psychotropic drugs; benzodiazepines may be 
 particularly problematic)
DeliriumDaytime drowsinessSleep disturbanceDepressionAnxiety
Physical
FallsFracturesDrug–drug and drug–alcohol interactions
Problems related to drug metabolism (e.g. renal and hepatic impairment)

1545
prescription medications, screening and treatment programmes 
for MUDs should also lead to considerable improvements in qual-ity of life, along with ﬁ  nancial and other savings.
Misuse of illicit drugs by older people is not generally a major 
problem at present, but it is virtually certain that consumption of illegal substances by people over 65 will increase in the future.
Greater awareness amongst physicians and other health care pro-
viders of the possibility of AUDs and MUDs in their older patients should lead to the development of more comprehensive and age-appropriate prevention and treatment strategies. At the levels of everyday clinical practice and public health policy, greater empha-sis should be placed on AUDs and MUDs in older people and further evaluation of dedicated ‘same-age’ treatment services and settings should be performed.
Website of National Institute on Alcohol Abuse and Alcoholism (NIAAA): 
www.niaaa.nih.gov

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896–905.8.5.3 Schizophrenia and 
paranoid disorders in late life
Estimates of the point-prevalence of paranoia and other psychotic 
symptoms among persons age ≥ 65 years have ranged from approx-
imately 4 per cent to 6 per cent,(1–3) and may be as high as 10 per 
cent among those age ≥ 85 years.(4) Although the majority of these 
symptoms occur as secondary psychoses in the context of Alzheimer’s disease or related dementias,
(5) the population of

(5) the population of 
people with schizophrenia is ageing along with the general ‘greying’ of the industrialized world, and mental health care for older adults with schizophrenia is expected to be an increasingly important public health concern.
(6)
Schizophrenia is typiﬁ  ed by the presence of two or more of the 
following categories of core symptoms: delusions, hallucinations, disorganized or catatonic behaviour, disorganized speech (or for-mal thought disorder), and negative symptoms (such as affective ﬂ attening, avolition, or social withdrawal).
(7) Older patients tend 
to have less severe positive symptoms (hallucinations, delusions, disorganized behaviour) than their younger counterparts, but there are few age-related differences in presence or severity of negative 
symptoms.
(8,9)

symptoms.
(8,9)
Most patients with schizophrenia and related primary psychotic 
disorders also have mild to moderate neurocognitive deﬁ  cits.(10)
There is considerable interpatient heterogeneity in terms of the 
severity of neuropsychological deﬁ  cits, but the level of these deﬁ  cits 
is a consistent and strong determinant of impairments in everyday functioning
(11) and competence or decisional capacity.(12)
In terms of late-life schizophrenia, one common division is 
between those with earlier onset in adolescence or early adulthood (prior to age 40 or 45 years) versus later-onset (onset ≥ age 40 or 45 
years). The latter group may comprise as many as 24 per cent of peo-ple with late-life schizophrenia.
(13) Relative to similarly aged patients

(13) Relative to similarly aged patients 
who had earlier onset, those with later-onset schizophrenia tend to have a higher prevalence of paranoid subtype and persecutory delu-sions, but better premorbid social-occupational functioning, fewer current disorganized symptoms, less severe (although not an absence of) negative symptoms, and less severe neuropsychological impair-ment. They are also more likely to be women, and tend to respond to lower doses of antipsychotic medication.
(3,14,15)  The two groups are 
similar in terms of severity of thought disorder,(16) although patients 
with very late onset schizophrenia-like psychosis (age of onset ≥ 60 
years) tend to have less severe formal thought disorder.(17)
Classiﬁ  cation systems
The term ‘schizophrenia’ was coined by Eugen Bleuler in the early 
20th century, but he wrote of ‘the schizophrenias’ (plural)(18) as an

1547
explicit acknowledgement of the substantial heterogeneity that 
characterizes this condition. Efforts to group ‘the schizophrenias’ into meaningful subtypes have been a key part of efforts to deﬁ  ne 
the syndrome itself.
(19) Most of the terms describing different sub-
types of schizophrenia in the current Diagnostic and Statistical 
Manual  (DSM-IV-TR)(7) and in the International Classiﬁ  cation of 
Diseases (ICD-10)(20) [such as paranoid, catatonic, hebephrenic 
(disorganized), and undifferentiated (simple) subtypes] overlap with the subtypes identiﬁ  ed by Kraepelin and or E. Bleuler a 
century ago. Other subtyping efforts have focused on a variety of dimensions such as positive and negative symptoms, cognitive functioning and/or course, but as true of the clinical subtypes in the DSM-IV-TR and ICD-10, there is invariably substantial intrasubtype heterogeneity.
(21)
In regard to late-life schizophrenia, one of the key nosological

(21)
In regard to late-life schizophrenia, one of the key nosological 
controversies over the past century has been whether or not the late onset form is actually schizophrenia. Kraepelin’s conception of dementia praecox  in 1896 was that the disorder was deﬁ  ned by onset 
in adolescence or early adulthood. By 1913, Kraepelin came to acknowledge that early onset was not a universal feature, but the emphasis on early onset remained a potent belief in the ﬁ  eld 
throughout most of the 20th century.
(22) On the other hand, inter-
est in late-onset schizophrenia has a long history, including seminal work by Manfred Bleuler, begun in the early 1940s with patients whose symptoms emerged at or after age 40 years.
(23)
The term ‘late-onset schizophrenia’ has occasionally been used 
interchangeably with the term late paraphrenia , although the latter 
was originally conceptualized as a more circumscribed psychosis with onset at age 60 or 65.
(24,25) Unfortunately, the terms ‘late-onset

(24,25) Unfortunately, the terms ‘late-onset 
schizophrenia,’ and paraphrenia  (with or without the epithet ‘late’), 
and a variety of age cut-offs have been used interchangeably and inconsistently over the years, resulting in considerable confu-sion in the literature.
(22,25) In a 1998 international consensus 
meeting on this topic, the group consensus suggestion was that the term ‘late onset schizophrenia’ be reserved for those with onset between ages 40 and 59 years, whereas the term ‘very late onset schizophrenia-like psychosis’ be used with those whose symptoms ﬁ rst manifest at age 60 or later.
(3)
None of the above schizophrenia onset-related categories is rep-
resented in the contemporary formal diagnostic systems. The 1980 version of the American Psychiatric Association’s Diagnostic and 
Statistical Manual  (DSM-III)
(26) arbitrarily excluded the diagnosis

(26) arbitrarily excluded the diagnosis 
of schizophrenia if symptoms did not emerge prior to age 45. This exclusion was dropped from the subsequent revision (DSM-III-R),
(27)
although the DSM-III-R required the speciﬁ  cation of ‘late onset’ if 
the prodromal phase of illness developed after 45. The latter is the only instance of ‘late-onset schizophrenia’ appearing as a named condition in one of the major nosological systems. Based on mounting empirical evidence that ‘real’ schizophrenia could mani-fest after age 45,
(13) the age of onset restrictions as well as the ‘late 
onset’ speciﬁ  er were dropped in the DSM-IV (28) and DSM-IV-TR.(7)
Similarly, there is no age-of-onset related restriction or speciﬁ  ca-
tion under the ICD-10.(20)
The diagnostic criteria for schizophrenia in the DSM-IV-TR and ICD-10 mention neither current age nor age of onset.

(7,20)  A key differential diagnosis with older adults is to rule out presence of 
a secondary psychosis.(29) For instance, among elderly patients, 
psychotic symptoms most commonly present in the context of dementia, such as Alzheimer’s disease, Parkinson’s disease, or dementia with Lewy Bodies.
(5) The pattern in any one patient may 
of course vary from normative trends, but in general among those with dementia-related psychotic symptoms, there is a greater pro-pensity for visual over auditory hallucinations, and bizarre content is less common in the delusions than in those of patients with primary psychotic disorders such as schizophrenia.
(30)
Delirium may also present as acute psychosis;(31) as with dementia,

(30)
Delirium may also present as acute psychosis;(31) as with dementia, 
visual hallucinations and delusions tend to be more common than auditory hallucinations, but the psychotic symptoms associated with delirium can be of any form.
(32) Given the high rates of polypharma-
cy among the elderly as well as age-related changes in pharmacokinet-ics, it is also important to consider pote ntial acute mental effects of the 
medications in isolation and in combination.
(33) Other differential 
diagnoses to consider among elderly patients are non-psychotic hal-lucinations related to bereavement or sensory deprivation.
(34,35)
Among the primary psychotic conditions, the standard differen-
tial diagnoses and considerations apply in terms of differentiating among schizophrenia, schizoaffective disorder, delusional disorder, brief psychotic disorder, substance-induced psychotic disorder, bipolar disorder with psychotic features, and major depressive disorder with psychotic features.
(7)

(7)
As was noted above, prevalence estimates of paranoia and other psychotic symptoms among persons age ≥ 65 years have ranged 
from approximately 4 per cent to 6 per cent,
(1–3) but these symp-
toms are most commonly in the context of a dementia or other medical condition. Estimating the lifetime prevalence of schizo-phrenia is a methodologically complex endeavour needing addi-tional research attention; recent estimates have ranged from approximately, 0.4 per cent to 1.0 per cent although estimates as high as 1.6 per cent have also been reported.
(36,37) The lifetime 
prevalence of schizophrenia is similar among men and women, and the majority of patients of either gender experience onset in adolescence or early adulthood.
(37) However, a consistent ﬁ  nding 
noted a century ago by E. Bleuler,(18) is that women tend to show 
later onset than men.(38)
Estimates of the lifetime prevalence of schizophrenia for persons

Estimates of the lifetime prevalence of schizophrenia for persons 
over age 65 have also varied, although the 95 per cent conﬁ  dence 
interval estimate from one recent comprehensive study was 0.58 to 1.45 per cent.
(37) There have been some epidemiological studies 
suggesting that the prevalence (current and lifetime) of schizo-phrenia among elderly persons is lower than that for the younger population. People with schizophrenia have higher mortality due to suicide and physical disorders,
(39,40)  so there are probably pro-
portionally fewer people with schizophrenia who survive to older age. However, the prevalence of schizophrenia in elderly patients may also have been underestimated in some of the earlier major epidemiological studies.
(41) For instance, the Epidemiologic

(41) For instance, the Epidemiologic 
Catchment Area study used the DSM-III criteria, but as was noted above, the DSM-III criteria for schizophrenia arbitrarily required 
onset of prodromal symptoms prior to age 45, so any cases of later-onset schizophrenia would have been excluded.
(41)8.5.3 schizophrenia and paranoid disorders in late life

SECTION 8  the psychiatry of old age 1548
Aetiology
The cause(s) of schizophrenia remains unknown. Both Kraepelin 
and E. Bleuler correctly suspected that there is a heritable vulnera-bility to schizophrenia, conﬁ  rmed by the substantially higher 
concordance rates among monozygotic twins (estimated at 40 to 50 per cent) relative to dizygotic twins (estimated at 5 per cent to 25 per cent).
(42, 43) The elevated risk of schizophrenia among 
ﬁ rst-degree relatives is present among those with schizophrenia 
onset in middle-age as well as those wither earlier onset relatives.(3)
Although some candidate genes have been identiﬁ  ed,(44) these 
efforts remain in an early stage of development. Also, given that even the monozygotic twin concordance rate is substantially below 100 per cent, non-genetic factors clearly have a role in the ultimate expression of the schizophrenia phenotype.
At present, the prevailing model of schizophrenia is that of

At present, the prevailing model of schizophrenia is that of 
neurodevelopmentally based aberrations in connectivity of key brain regions and systems.
(45, 46)  Evidence for the neurodevelop-
ment component includes an elevated risk of schizophrenia associ-ated with certain pre- or peri-natal insults or stresses, an increased prevalence of minor facial anomalies among patients with schizo-phrenia, and an increased prevalenc e of subtle c hildhood abnormal-
ities in motor, cognitive, and/or psychosocial development among those who later develop schizophrenia.
(45) At the level of neuropa-
thology, Kraepelin expressed some suspicion of involvement of the prefrontal and temporal lobes;
(47) these remain areas of interest in 
schizophrenia research although the current focus is on functional (rather than gross structural) impairments related to the connec-tions among such brain regions or systems.
(46)

(46)
Schizophrenia is generally a chronic condition, but not necessarily a constantly sustained one in that many patients experience one or more periods of several years of sustained recovery over their lifes-pan, but periods of relapse are also common.
(48) As with other 
dimensions of this disorder, the long-term course of schizophrenia is also characterized by heterogeneity among patients, as well as methodological challenges in interpreting varied ﬁ  ndings in the 
empirical literature.
(49) Some of the factors that have been cited 
as associated with worse prognosis include poor premorbid func-tioning, very early and gradual/insidious onset of symptoms, male gender, and a relative prominence of negative symptoms.
(49,50) In a 
recent review of ten long-term longitudinal outcome studies, Jobe and Harrow
(48) found that the estimates of ‘good outcome’ ranged

(48) found that the estimates of ‘good outcome’ ranged 
from 21 to 57 per cent. Since most of the long-term research on the course of schizophrenia has been of younger patients as they age, there remains a clear need for longitudinal research to document changes among patients as they age from their 60s, 70s, and 80s. Nonetheless, empirical data do not seem to support Kraepelin’s initial suggestion that dementia praecox  is characterized by a course 
of progressive decline.
(49) In fact, there may be some modest age-
related improvements in positive symptoms and perhaps other aspects of psychopathology.
(8) Although there is a small subset of 
‘poor outcome’/ chronically institutionalized patients who seem to be at added risk for cognitive and functional decline in older 
age,
(51) for most patients there is generally no increased (beyond

age,
(51) for most patients there is generally no increased (beyond 
age normal) decline in cognitive functioning among those with early or middle-age onset.
(52, 53)Treatment
Contemporary treatment guidelines for schizophrenia in older adults parallel those for younger adults in that a combination of pharmacological and psychosocial interventions is recommended.
(54)

(54)
Although treatment with antipsychotic medications is a mainstay of effective treatment and management of late-life schizophrenia, selection of the appropriate type and dose of antipsychotic medica-tion in the elderly may be complicated by age-related factors. One of the primary concerns with conventional neuroleptic medi-cations is that they can cause iatrogenic motor abnormalities; older adults are at even greater risk than younger patients to develop tardive dyskinesia and extrapyramidal symptoms, or EPS, (especially parkinsonism) from conventional neuroleptics.
(55) The

(55) The 
newer (‘atypical’ or ‘second generation’) antipsychotic medications have lower (although not absent) associated risk of tardive dyski-nesia and EPS, though risks for these motor side effects also vary from one atypical antipsychotic to another.
The current APA treatment guidelines for schizophrenia indicate 
‘Second-generation antipsychotics are generally recommended over 
ﬁ  rst-generation agents because of their signiﬁ  cantly lower risk of inducing extrapyramidal symptoms and tardive dyskinesia in older persons . . . However, the second-generation agents have other clini-cally signiﬁ  cant and common side effects  (pp. 33–34). ’ In addition to 
concerns about potential sedation, orthostatic hypotension, and other potential physical or medical side-effects from the newer medications, there has been recent concern about the potentially serious metabolic and cardiovascular side effects.
(56) Overall,

(56) Overall, 
atypical agents (with the exception of clozapine) have not shown superior efﬁ  cacy for schizophrenia in direct comparisons with typ-
ical antipsychotics.
(57) This fact, combined with the lower cost of 
typical agents, has prompted some experts to question the use of atypical antipsychotics as ﬁ  rst-line pharmacotherapy for schizo-
phrenia. In the absence of more deﬁ  nitive evidence, clinicians 
should discuss these various advantages and disadvantages of speciﬁ  c drugs with patients when choosing drug therapy.
For most antipsychotics (typical or atypical), older adults with 
schizophrenia generally respond to 50–75 per cent of the doses needed in younger patients and often cannot tolerate the full young adult dose.
(58) Side effects that are especially problematic in older

(58) Side effects that are especially problematic in older 
adults include anticholinergic effects (e.g. constipation, confusion, urinary retention), orthostatic blood pressure changes (which may lead to falls), and reported increases in stroke and death among persons with dementia receiving antipsychotics (as dementia, of course, becomes more prevalent with increasing age).
Antipsychotic medications are helpful in managing the psycho-
pathologic symptoms of schizophrenia, especially the so-called ‘positive symptoms’ such as delusions and hallucinations, but they are not a cure. Medications also tend to have little beneﬁ  t for the 
‘negative’ (e.g. apathy, anhedonia) and cognitive symptoms of the illness. Furthermore, many patients continue to have residual functional disability despite resolution of positive symptoms of psychosis. Thus, the importance of adjunctive treatment with 
evidenced-based psychosocial interventions in schizophrenia 
is being increasingly recognized.

(59) For instance, investigators 
at our Research Center have developed or adapted, and validated a number of effective adjunctive psychosocial interventions for older patients with schizophrenia or related psychoses; these include Cognitive Behavioral Social Skills Training,
(60)

1549
Functional Adaptation Skills Training,(61) diabetes management/
lifestyle modiﬁ  cation,(62) and vocational rehabilitation/supported 
employment.(63) These efforts address a number of dimensions of 
schizophrenia that are unaffected by pharmacologic treatment alone.
As noted above, schizophrenia is a chronic condition. In addition, to speciﬁ  c therapies previously described, managing this complex

and devastating illness requires careful attention to clinician-patient rapport. This is especially true in persons with severe paranoia and in those who lack insight into their illness. Providing care for someone who does not trust anyone or who sees no reason for treatment can be challenging, but these obstacles can often be overcome by involving family, listening empathically, avoiding premature confrontation about delusions, respecting the increased interpersonal distance many patients require, and identifying the patient’s goals and priorities. Management of schizophrenia may often be optimized by multi- and interdisciplinary care to address the many ways in which the illness affects patients’ lives. Because there tends to be a high degree of medical comorbidity in persons with schizophrenia (especially older adults), integration of primary care and psychiatric care is often needed. Due to normal age-related physical changes, polypharmacy, and the higher risk of medication

schizophrenia (especially older adults), integration of primary care and psychiatric care is often needed. Due to normal age-related physical changes, polypharmacy, and the higher risk of medication side-effects, the long-term management of schizophrenia in older adults demands frequent monitoring of symptoms, overall health, and side-effects. Cross-discipline collaborative care and continuity with the same clinicians can help ensure older persons with schizo-phrenia achieve the best possible outcomes.

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8.5.4 Mood disorders in the elderly
This chapter considers some of the commonly asked questions 
about mood disorders in later life. Is depression in later life a dis-tinct clinical syndrome? How common is it? Is there an organic link, for example to cerebral changes, and if so, is there an increased risk of later dementia? Is it more difﬁ  cult to diagnose and treat late-

life depression, and once treated, is the outcome good, bad, or indifferent? The emphasis will be on depression but bipolar disor-der and mania will also be considered.
The main mood disorders which older people suffer are classiﬁ  ed 
as: depressive episode, dysthymia, bipolar disorder, and organic mood disorder. Depressive illness and major depression are terms often used synonymously with depressive episode. Current classiﬁ  -
catory systems, notably The World Health Organization ICD10 and the DSM Version IV of the American Psychiatric Association, are described in Chapter 4.5.3.

1551
Depressive episode
Other than more frequent so matic and hypocho ndriacal co mplaints, 
patients with depression in later life are little different, symptom-atically, to younger adults.
(1) An exception may be the recently 
described ‘vascular depression’ (depression linked to small vessel disease of the brain), in which depressive ideation is less but cogni-tive impairment and apathy greater. In most cases then the patho-plastic effects of ageing and ill-health are what mainly inﬂ  uence the 
presentation of depression in later life (Table 8.5.4.1).
An overlap of symptoms due to associated physical ill-health  may 
lead to diagnostic difﬁ  culty, and determining whether a symptom 
has arisen predominantly because of affective disorder or a medical condition can be difﬁ  cult for those without the necessary experience.
Older depressed patients may minimize feelings of sadness  and 
instead become hypochondriacal  (morbidly preoccupied with a 
fear of illness).

(1) Late-onset neurotic symptoms  (severe anxiety ,
phobias ,obsessional compulsive phenomena or hysteria ) are usually 
secondary to depressive illness. Any act of deliberate self-harm
suggests depression, as elderly people rarely take ‘manipulative’ overdoses. An overdose in an older person should never be dis-missed because its effects, in purely medical terms, were trivial. All require psychiatric assessment. Severe depression may mimic

dementia. Table 8.5.4.2 highlights the main differences between progressive dementia and the pseudodementia of depression. Pseudodementia is a term which is perhaps waning in use as it has become clear that depressive disorder is commonly associated with cognitive impairment, which may not be reversible, even with adequate treatment of depression. Pseudodementia is often applied to an older depressed patient who, on presentation, appears very 
confused, with frequent ‘don’t know’ responses. However, the onset of confusion is acute, easily dated, the patients convey their despair

confused, with frequent ‘don’t know’ responses. However, the onset of confusion is acute, easily dated, the patients convey their despair 
non-verbally, and, unlike the person with degenerative dementia, complain vociferously about their memory. Cortical signs (aphasia, apraxia, etc.) suggest a primary dementia with a super-added depression rather than depressive pseudodementia. Wandering off and getting lost suggests dementia but occasional cases are seen of fugue states caused by severe depression mimicking disorganized behaviour in dementia. The key is a good history.
An unusual behavioural disturbance  may occasionally be a leading 
symptom of depression. Examples include the onset of incontinence in an older person who feels trapped in a situation of resented dependency in a residential or nursing home, late-onset alcohol abuse or, rarely, shoplifting.(a) Vascular depression

In vascular depression, vascular disease is judged to predispose, precipitate, or perpetuate depressive symptoms. Evidence (summa-rized by Baldwin
(2)) includes the following. There is a high rate of 
structural brain abnormalities in both white matter and basal gan-glia grey matter on imaging and on post-mortem examination of older patients with depressive disorder, notably with a late age of onset. Psychomotor change, apathy, and executive dysfunction (leading to slowed responses, failure of initiation, impersistence in tasks, and inefﬁ  cient memory) occur characteristically in such 
patients. Strategic lesion location, sufﬁ  cient to disrupt subcortical-
frontal circuitry, is associated with poorer depression outcomes, and progression of such lesions is associated with later incident cases of depression in those not already depressed. The concept of vascular depression is discussed critically under aetiololgy.

The psychiatric history should include a collateral history as well as drug evaluation (prescribed, ‘borrowed’ , and over-the-counter) and alcohol intake. A cognitive screening test should always be undertaken. A physical evaluation should focus on possible disor-ders causing an organic mood disorder (Table 8.5.4.3), including medication. Non-selective β-blockers, calcium antagonists, benzo-
diazepines, and systemic corticosteroids were the main culprits in one study.
(3)
Screening questionnaires can be used to help diagnose depression,

(3)
Screening questionnaires can be used to help diagnose depression, 
especially in settings such as medical wards where the prevalence is high, but their results must be informed by clinical judgement. The Geriatric Depression Scale (GDS) (Geriatric Depression Scale website http://stanford.edu/~yesavage/GDS.html) is widely used. It focuses on the cognitive aspects of depressive illness rather than physical depressive symptomatology, and has a simple ‘yes/no’ for-mat (Table 8.5.4.4). It loses speciﬁ  city in severe dementia but per-
forms reasonably well in mild to moderate dementia. For rapid screening four questions (1, 3, 8 and 9) can be used.
(b) Investigations
Table 8.5.4.5 summarizes investigations appropriate for a ﬁ  rst

Table 8.5.4.5 summarizes investigations appropriate for a ﬁ  rst 
episode of depression and a recurrence. A guiding principle is that elderly people are in a more precarious state of homeostasis with their environment because they have less physiological reserve. Table 8.5.4.1  Factors inﬂ  uencing the presentation of depression in 
Overlap of symptoms of physical disorder with those of the somatic 
symptoms of depression
Tendency of older people to minimize a complaint of sadness and instead 
become hypochondriacal
Late-onset neurotic symptoms (severe anxiety, obsessional compulsive 
symptoms, hysteria) which mask depression
Deliberate self-harm which seems medically trivial
PseudodementiaBehavioural disturbance such as alcohol abuse or shoplifting8.5.4 mood disorders in the elderly
Table 8.5.4.2  Characteristics distinguishing depression 
(‘pseudodementia’) from dementia
Dementia Depression
Insidious Rapid onset

Symptoms usually of long duration Symptoms usually of short durationMood and behaviour ﬂ  uctuate Mood is consistently depressed‘Near miss’ answers typical ‘Don’t know’ answers typical
Patient conceals forgetfulness Patient highlights forgetfulness
Cognitive impairment relatively stable Cognitive impairment ﬂ  uctuates 
greatly
Higher cortical dysfunction evident Higher cortical dysfunction absent

SECTION 8  the psychiatry of old age 1552
Severe depression in a 75-year-old may lead to quite serious meta-
bolic derangement which would be unlikely in a ﬁ  t 35-year-old.
An electroencephalogram (EEG) can help in differentiating 
depression from an organic brain syndrome such as delirium or an 
early dementia. A brain scan is only performed if clinically indi-
cated, for example a rapid-onset depression with neurological symptoms or signs. The Dexamethasone Suppression T est (DST) is less speciﬁ  c for depressive illness than was ﬁ  rst thought. It cannot 
reliably differentiate dementia from depression.
Organic mood disorder  is diagnosed when a direct aetiological 
link can be established between the onset of the mood disorder and an underlying systemic or cerebral disorder (including dementia), or an ingested substance such as medication or alcohol.
Bipolar disorder  is covered later. Psychotic illness  (schizophrenia

Bipolar disorder  is covered later. Psychotic illness  (schizophrenia 
or delusional disorder) may present with marked depressed affect but other symptoms are present. A common depressive delusion in old age is hypochondriasis and sometimes it is difﬁ  cult to decide 
whether the patient has a psychotic or an affective disorder. Interpretation depends on which symptoms predominate; if they occur together, it may be appropriate to use the term schizoaffective disorder.Dysthymia  chieﬂ  y occurs in younger adults but may occur in 
later life in association with chronic ill-health. Where there is a clear onset of depressive symptoms within 1 month of a stressful life event without the criteria for a depressive episode being met, then an adjustment disorder  may be diagnosed.
In the United Kingdom, pervasive depression (a term denoting a

In the United Kingdom, pervasive depression (a term denoting a 
depressive syndrome that a psychiatrist would regard as warranting intervention) is found between 8.6 and 14.1 per cent of elderly people living at home. The prevalence of a depressive episode is between 1 and 4 per cent of elderly people living at home.
(4) The 
ﬁ nding of a high rate of depressive symptoms but a much lower 
rate of depressive episodes is an epidemiological dilemma which is discussed in Chapter 4.5.4. It is likely that current classiﬁ  cation Table 8.5.4.3  Common medical illnesses and drugs that may cause 
organic mood syndromes
Medical conditions Central-acting drugs
Endocrine/metabolic Anti-hypertensive drugs
Hypo/hyperthyroidism β-blockers (especially non-selective)
Cushing’s disease Methyldopa
Hypercalcaemia Reserpine
Sub-nutrition Clonidine
Pernicious anaemia Nifedipine, calcium channel agents
Organic brain disease Digoxin
Cerebrovascular disease/stroke Steroids

CNS tumours Analgesic drugs
Parkinson’s disease OpioidsAlzheimer’s disease and vascular 
 dementiaIndomethacin
Multiple sclerosis Anti-parkinson
L-Dopa
Occult carcinoma Amantadine
Pancreas TetrabenazineLung Psychiatric drugs
Chronic infections Neuroleptics
Neurosyphilis Benzodiazepines
Brucellosis Miscellaneous
Neurocysticercosis SulphonamidesMyalgic encephalomyelitis AlcoholAIDS InterferonTable 8.5.4.4  Geriatric Depression Scale
Instructions : Choose the best answer for how you have felt over the past week .
 1. Are you basically satisﬁ  ed with your life? No
 2. Have you dropped many of your activities and interests? Yes
 3. Do you feel your life is empty? Yes
 4. Do you often get bored? Yes
 5. Are you hopeful about the future? No

2. Have you dropped many of your activities and interests? Yes
 6. Are you bothered by thoughts you can’t get out of your head? Yes
 7. Are you in good spirits most of the time? No
 8. Are you afraid something bad is going to happen to you? Yes
 9. Do you feel happy most of the time? No
10. Do you often feel helpless? Yes
11. Do you often get restless and ﬁ  dgety? Yes12.  Do you prefer to stay at home, rather than going out and doing new 
things? Yes
13. Do you frequently worry about the future? Yes
14.  Do you feel you have more problems with your memory than most? 
Yes
15. Do you think it is wonderful to be alive now? No
16. Do you often feel downhearted and blue (sad)? Yes
17. Do you feel pretty worthless the way you are? Yes
18. Do you worry a lot about the past? Yes
19. Do you ﬁ  nd life very exciting? No

20. Is it hard for you to start on new projects (plans)? Yes21. Do you feel full of energy? No
22. Do you feel that your situation is hopeless? Yes
23.  Do you think most people are better off (in their lives) than you 
are? Yes 
24. Do you frequently get upset over little things? Yes25. Do you frequently feel like crying? Yes
26. Do you have trouble concentrating? Yes
27. Do you enjoy getting up in the morning? No
28. Do you prefer to avoid social gatherings (get-togethers)? Yes
29. Is it easy for you to make decisions? No30. Is your mind as clear as it used to be? No
Notes : (1) Answers refer to responses which score ‘1’; (2) bracketed phrases refer to

Notes : (1) Answers refer to responses which score ‘1’; (2) bracketed phrases refer to 
alternative ways of expressing the questions; (3) questions in bold are for the 15-item version. Threshold for possible depression: >/=11 (GDS30); >/=5 (GDS15); >=2 (GDS4).

1553
systems overlook many of the late-life depressions found in 
community studies.
Depression in later life, whether major or ‘minor’ , is associated 
with worsened medical morbidity, disability, and increased health utilization.
(1) Co-morbidity from physical disorder or cognitive 
impairment is the main determinant of prevalence. Handicap, the disadvantage imposed by a physical impairment and attendant disability, is a further strong predictor of depression.
(5) This 
matters because handicap is amenable to social intervention.
In residential care, nursing homes and medical wards the rates 
are between 20 and 40 per cent.
Aetiology

(5) This 
Aetiology
The risk factors for depression in later life are discussed in Chapter 4.5.5. A depressive episode usually arises from a combina-tion of vulnerability factors along with a triggering (precipitating) adverse life event. Avoidant and dependent personality types are associated with late-life depression, and a lifelong lack of a capacity for intimacy is another risk factor.
(6) Precipitating life 
events occur at a similar frequency to other age groups, although health-related events are more common among older people.
(6)
The concept of vascular depression suggests new aetiological 
insights.(2) However, criticisms against vascular depression as a dis-
tinct subtype include the difﬁ  culty in establishing a temporal link

tinct subtype include the difﬁ  culty in establishing a temporal link 
between depression onset and vascular disease and that, if causal, vascular disease is likely to have been present well before old age. Furthermore, in studies of vascular depression the direction of causality is unclear since patients with vascular disease have a high rate of depression, and depression appears to worsen vascular disease, perhaps by direct effects on blood vessel endothelial func-tion and indirectly through poor self-monitoring of health and poor adherence to medical drugs.If conﬁ  rmed, the vascular depression hypothesis could lead

to antidepressant strategies aimed at improving the underlying vascular impairment as well as mood. In the meantime, a patient presenting late-onset depression should be thoroughly investigated for vascular disease as a potential aetiological contributory factor which should be optimally treated along with the depression.
Across all age groups depressive disorder is prone to persistence. Beekman et al.
(7) followed 277 community-dwelling subjects, aged 
over 55 (most over 75), from a Dutch epidemiological survey. Using multiple assessments of mood over a 6-year period, they found almost half the sample was depressed for more than 60 per cent of the time. Twenty three per cent had true remissions, 12 per cent remissions with recurrence, a third a chronic-intermittent course; another third had chronic depression. Outcomes reported from the community and medical ward patients are worse than those of depressed patients under psychiatric care,
(8) possibly linked to

(8) possibly linked to 
undertreatment in the non-specialist settings.
(a) Comparative outcome
Mitchell and Subramaniam(9) reviewed the literature between 1966 
and July 2004, ﬁ  nding 24 publications which could be used to assess 
outcomes between different age groups. Overall the authors concluded that episodes of depression remitted in later life as well as in other times but with a greater risk of relapse. Two factors seemed to explain this: age of onset (recurrent depression from earlier life conferring a poorer prognosis) and medical comorbidity (with a worse prognosis linked to a later onset). Although these mechanisms differ, the high risk of relapse in late-life depression highlights the need for effective continuation and maintenance phases of treatment, regardless of age of onset.
Mortality
A number of studies show that depression is an independent risk factor for increased mortality,
(1) not accounted for by suicide.

Mortality
(1) not accounted for by suicide. 
Following a cohort of 652 depressed and non-depressed subjects over 3.5 years, Geerlings
(10) found that duration, chronicity, 
and increasing symptoms from baseline were all linked to a higher risk of death, leading them to suggest that adequate treatment may reduce this effect. Physical illness, occult disease (e.g. a carcinoma), poor self-monitoring of health, inactivity, poor adherence to treatments, and effects on the hypothalamic-pituitary-adrenal axis or other endocrine systems are possible factors.
Factors predictive of outcome

Clinical features that have been shown to be associated with a poorer outcome, include a slower initial recovery, more severe initial depression, duration of illness for more than 2 years, three or more previous episodes, a previous history of dysthymia, psychotic symptoms, and cerebrovascular disease (including vascular depression). Other factors that may affect outcome adversely are chronic stress associated with a poor environment, crime, and poverty as well as a new physical illness, becoming a victim of crime, and poor perceived social support.
The practical message is that to improve the prognosis of 
depression one must treat episodes early and vigorously and attend to the patient’s social supports, and milieu.Table 8.5.4.5  Investigations for depression in later life
Investigation First episode Recurrence
Full blood count Yes Yes
Urea and electrolytes Yes YesCalcium Yes YesThyroid function Yes If clinically indicated, or 
more than 12 months

more than 12 months 
elapsed
B
12Yes If clinically indicated, or 
elapsed
Folate Yes If clinically indicated (for 
example recent poor diet)
Liver function Yes If indicated (for example 
suspected or known 
alcohol misuse)
Syphilitic serology If clinically indicated 
(for example 
relevant neurological 
symptoms)Only if clinically indicated
CT (brain) If clinically indicated If clinically indicated
EEG If clinically indicated If clinically indicated8.5.4 mood disorders in the elderly

SECTION 8  the psychiatry of old age 1554
(a) Does depressive disorder predispose to later dementia?
There is growing evidence from epidemiological studies that depres-
sion is a risk factor for later cognitive impairment or dementia.(11)
Why this might be so is not clear but it is known that chronic depres-sion is associated with hippocampal atrophy in older patients,
(12) and 
that depressed patients may adopt unhealthy lifestyles, which can aggravate the risk factors for vascular disease and later dementia.
Treatment

(12) and 
Treatment
Multi-modal management (pharmacological, psychological, and social) within a multidisciplinary framework is as important in late-life as it is at other times of life. Attending to an elderly depressed person’s physical health needs, physical environment, and social needs is essential. The goal is remission of all symptoms and not merely improvement, as residual symptoms increase the chance of chronicity. Ageing and frailty result in increased depen-dency and less ability to adapt in a ﬂ  exible way to the kinds of

adversity that maintain depression. T o give a simple example, good chiropody aimed at optimizing mobility can have a major positive impact alongside medical intervention, but no one aspect of treat-ment should be prioritized over another. Another important prin-ciple is patient-centredness. This should include giving the patients as much choice as possible regarding their treatment. Many older depressed patients, if asked, would prefer a psychological approach 
to medical management and there is good evidence that psycho-
logical treatments work well in older adults.
(13) Resource limitations 
are understood, but age alone should not determine the likelihood of receiving a psychological intervention, if preferred.
Collaborative care, whereby, a depression care manager (usually

Collaborative care, whereby, a depression care manager (usually 
a nurse, psychologist, or social worker) coordinates the care and works closely with both primary care physician and psychiatrist, is an important model for improving outcomes. In the largest study to date, ‘IMPACT’ from the United States, involving 1801 depressed primary care patients (major depression, 17 per cent; dysthymia, 30 per cent; or both, 53 per cent), at 12 months the Number-Needed-to-Treat (NNT) was highly signiﬁ  cant at four in those 
receiving the intervention.
(14)
General principles of pharmacological management include: 
building a therapeutic partnership with the patient; explanation of how and when antidepressants work; addressing adherence through building therapeutic concordance; tailoring antidepressants drug to the patient; arranging appropriate follow-up.

Altered pharmacokinetics, different pharmacodynamics, a greater 
chance of polypharmacy and hence drug interactions and reduced compensatory mechanisms are all important factors which bear upon treatment response in late-life depression.
(15) An important 
practical consequence is to be mindful of greater inter-individual variation in drug-handling in older patients. Patients worry about antidepressants being addictive, which they are not, and that 
depression means ‘senility’ , which it does not. Psychoeducation is 
important and can improve adherence to medication recommen-dations. Recommended starting and therapeutic dosages are listed in Table 8.5.4.6. These are average doses. For some drugs, notably the tricyclics, there is a very wide therapeutic range and higher levels may be required, provided they are tolerated.
A Cochrane systematic review of Randomized Controlled Trials 
(RCT)

(RCT)
(16) found efﬁ  cacy for antidepressants over placebo in late-life major depression. However, the analysis could only ﬁ  nd 17 suitable 
studies (two of SSRIs). The NNT averaged four, but was higher for SSRIs. In a further Cochrane systematic review of studies including patients aged over 55 (29 trials), there was no difference in efﬁ  cacy 
between tricyclics and SSRIs, but tricyclics were associated with higher withdrawal rates due to side-effects. Patients receiving tricy-clic-related antidepressants (Mianserin or Trazodone) had a similar withdrawal rate to SSRIs, leading the authors to conclude that tricy-clic-related antidepressants may offer a viable alternative to SSRIs in older depressed patients. The analysis also investigated ‘atypical’ antidepressants but it was not possible to make recommendations because of low statistical power. Atypicals included the important

antidepressants reboxetine, venlafaxine, and mirtazapine.
(17)
More recent RCTs have suggested less positive results.(18) Trials 
involving older adults and with venlafaxine, ﬂ  uoxetine, citalopram, 
and escitalopram showed these drugs to be no more effective than placebo. Sertraline and duloxetine were superior to placebo but remission rates, as opposed to response rates, were relatively low in all these studies. Trials which are of insufﬁ  cient duration and the 
use of antidepressants for milder depressions, for which they are ineffective, are possible factors.
(b) Depression in special patient groups
A Cochrane systematic review of antidepressants for depression in dementia found ‘weak’ evidence for their effectiveness,
(19)
but there were few admissible trials. This does not mean 
Table 8.5.4.6  Suggested starting and therapeutic doses for 
antidepressants in the United Kingdom
Drug Average therapeutic 
dosesaAverage starting doses
Amitriptyline 75–100 25

Clomipramine 75–100 10
Dosulepin (dothiepin) 75–150 25–50Imipramine 75–100 10–25
Nortriptyline 75–100 10–30
Lofepramine 140–210 70–140
SNRIs
Venlafaxine 150 37.5 bd
Duloxetine 60 30–60
SSRIs
Fluoxetine 20 20
Fluvoxamine 100–200 50–100
Paroxetine 20 20
Sertraline 50–150 50Citalopram 20–40 20
Escitalopram 10 5
Reversible monoamine oxidase 
 inhibitor  (RIMA)
Moclobemide 150–600 150 bd
5-HT2 receptor blocker
Trazodone 100–300 100
NASSA
Mirtazapine 15–30 30
Others
Mianserin 30–90 30
a See text.

1555
antidepressants are ineffective in depression-related dementia but 
there is a high rate of spontaneous recovery of depression compli-cating dementia so that ‘watchful waiting’ is reasonable for mild-to-moderate cases.
There is little trial data for individual antidepressants in patients 
with common medical disorders, but in the previously mentioned IMPACT research, both physical function and pain were improved in participants who received active case management compared to usual care.
(20,21)
Depression post-stroke is common. A high rate of spontaneous 
recovery occurs, especially in the ﬁ  rst 6 weeks. Studies are under-
way to assess whether repetitive Transcranial Magnetic Stimulation (rTMS) may be helpful in post-stroke depression. TCAs and SSRIs in standard dosages are effective in post-stroke emotionalism.
(c) Choice of antidepressant
Tricyclics  often cause postural hypotension, which may lead to

Tricyclics  often cause postural hypotension, which may lead to 
unpleasant dizziness or dangerous falls. Secondary amine tricyclics are generally safer in this respect than tertiary drugs. Poor left ven-tricular function is a risk, and so are diuretics or antihypertensive medication. Delirium is more likely in medically ill patients.
Behavioural toxicity (affecting vigilance, reaction times, etc.) has 
been largely ignored in the elderly. Now that so many older people drive and pursue other activities demanding high levels of vigi-lance, this must be addressed. The SSRIs  are safer in this respect 
than tricyclics, except for lofepramine which causes less impair-ment than the older tricyclics. Mirtazepine  enhances noradrenergic 
and serotonergic function via antagonism at the pre-synaptic α
2
receptor. Differences in pharmacodynamics and pharmacokinetics 
are minimal with age. The side effect proﬁ  le is similar to tricyclics;

2
are minimal with age. The side effect proﬁ  le is similar to tricyclics; 
weight gain and sedation can be troublesome. Duloxetine , like ven-
lafaxine is a dual-acting drug. The latter has been subject to cau-tions, regarding heart disease, at present in the United Kingdom, although recent restrictions have been lifted. Duloxetine has some RCT evidence in older depressed adults.
(22) Although a special diet 
with moclobemide  is not required, patients should be aware of drug 
interactions with painkillers and other antidepressants. Co-prescriptions of tricyclic and SSRIs should be avoided. A wash-out period of around 4–5 half-lives of the drug and any active meta-bolite is advised when transferring from a tricyclic or SSRI to moclobemide (but not from moclobemide to a tricyclic or SSRI).
(d) Failure to respond to initial treatment

If a patient has made minimal or no recovery after 4 weeks of treat-ment at optimal dose, then the chances of recovery are slim.
(23) The 
antidepressant may be changed to one of another class but if the patient shows at least 25 per cent improvement and is on an improving trajectory, then augmentation with lithium or a psycho-logical intervention should be considered (see below). Electroconvulsive Treatment (ECT) is safe and effective in older patients. It is recommended when drug treatment has failed, when the patient is in danger of inanition or is acutely suicidal and is probably the treatment of choice for psychotic depression.
(e) Continuation treatment
Most relapses occur in the ﬁ  rst 12 months,(24) so that this is a

Most relapses occur in the ﬁ  rst 12 months,(24) so that this is a 
reasonable time for continuation therapy. Patients must be educated about why they should continue to take medication even when feeling better. In psychotic depression anti-psychotic medication should be continued for 6 months and gradually withdrawn if the patient is well. Following ECT, medication should be continued to 
avoid relapse. Limited evidence suggests either continuing antide-pressants at the acute treatment dose or using lithium.
Older people have been shown to beneﬁ  t substantially from 
maintenance therapy,
(25) even after a ﬁ  rst episode.(24) Maintenance 
treatment is considered later.
(f) Resistant depression

Data in the elderly are sparse but the most important consideration is a rational stepped care approach. Before moving up the steps of treatment, the following should be addressed: is the diagnosis correct (for example has a psychotic depression been overlooked)? Is poor tolerance a reason for non-recovery? Does the patient take the tablets? Have psychosocial reinforcing factors (for example, family conﬂ  ict) been addressed? The steps themselves include

optimizing the dose of antidepressant (relevant mainly for older tricyclic antidepressants), changing from one class of antidepressant to another, augmentation with lithium or a psychological inter-vention and combining antidepressants (for example, a SSRI plus mirtazepine). Finally ECT should be considered as it remains the most effective antidepressant treatment. Using such an approach 80 per cent of patients in one study responded.
(26)
(g) Psychological therapies
Cognitive behavioural therapy (CBT), Interpersonal Psychotherapy (IPT), and psychodynamic psychotherapy have been shown to work in older people,
(13) including in group format. CBT and IPT 
along with family interventions are discussed elsewhere. Problem-solving Treatment (PST) addresses the here and now, focusing on current difﬁ  culties and setting future goals.
Psychological interventions may also be important in relapse 
prevention. Reynolds et al.
(27) showed in a study of older patients

(27) showed in a study of older patients 
that monthly IPT given in the continuation phase of treatment was more effective than routine care, with combined IPT and antidepressant therapy being the most effective strategy. However, the same group were unable to replicate this in a later study with a group of patients who were somewhat older.
(25)
Anxiety management can be an effective adjunctive treatment 
for depressed patients, especially those recovering from depression but left with residual anxiety, low conﬁ  dence, or phobic avoidance,

for depressed patients, especially those recovering from depression but left with residual anxiety, low conﬁ  dence, or phobic avoidance, 
any of which can undermine functional improvement. T echniques include progressive relaxation, either alone with a commercial tape, or in groups. Exercise and activity are important both to avoid depression and counter it. Behavioural activation is a technique which can overcome the withdrawal and apathy that so often exists in late-life depression. It works by helping the patient develop a schedule of activities, agreed with the patient, with or without a written diary to support implementation.
Work to support the family and main caregivers is also impor tant.
(a) Primary prevention
Many prevalent diseases of later life are associated both with 
depression as well as lifestyle factors: diet, exercise, and obesity. Cole and Dendukuri

(28) carried out a meta-analysis of risk factors 
for late-life depression, ﬁ  nding ﬁ  ve which were robustly linked to it. 
These were bereavement, sleep problems, disability, prior depression, and female gender. Some of these are amenable to a public health preventative approach.8.5.4 mood disorders in the elderly

SECTION 8  the psychiatry of old age 1556
Those most vulnerable to depression will often be in touch 
with a home care services. This is one area where education about detection could be usefully targeted. Another example is the staff of nursing homes where depression is highly prevalent. Postgraduate training of general practitioners is another way of improving detection via the ‘ﬁ  lter’ of primary care.
(b) Secondary prevention
Maintenance treatment with a tricyclic,(24) the SSRIs citalopram(29)
and paroxetine(25) or a combining medication with a psychological 
treatment(27) are effective prevention strategies.
Expert guidelines(30) recommend a minimum of 12 months 
continuation treatment for a ﬁ  rst episode, 24 months for a second,

continuation treatment for a ﬁ  rst episode, 24 months for a second, 
and at least 3 years for three or more episodes. Some clinicians recommend lifelong treatment with antidepressants following even a single episode of major depression on the grounds that a substantial later period morbidity might be reduced. This must be balanced against an increased risk of side effects as patients age.
(c) Tertiary prevention
Often the emphasis is on basic explanations and on simple instruc-tions about how to manage problems such as frequent hypochon-driacal complaints or apathy. Although respite care is usually associated with dementia, there is occasionally a case for it in those with chronic treatment-resistant depression, in order to allow the relative(s) a break.

Practice guidelines for bipolar disorder are available from the internet. Two are: British Association of Psychopharmacology  (2003)
(31)—http://
www.bap.org.uk/consensus/bipolar_disorder.html and the National Institute for Clinical Excellence (NICE) (2006) .
(32) http://
www.nice.org.uk/page.aspx?o=CG38.
Mania
Clinical descriptions of mania in late life often portray it as atypical. However, Broadhead and Jacoby
(33) found few clinical differences 
between 35 manic patients over the age of 60 compared to 35 y ounger
manic patients, aged below 40. The younger manic patients were 
more severely ill but there was no support for the often-held view 
that there is a greater depressive admixture in older patients.
The main differential diagnosis of mania in late life lies between a 
late-onset manic episode and bipolar disorder. In later presentations of bipolar disorder the time between depression and ﬁ  rst manic

late-onset manic episode and bipolar disorder. In later presentations of bipolar disorder the time between depression and ﬁ  rst manic 
episode can be us much as 15 to 40 years or more. Given this long latency it is easy to overlook bipolar disorder unless a thorough history is taken.
Although only about 10 per cent of new onset cases of bipolar disorder occurs after the age of 50 they account for proportionally greater morbidity. Changing demography makes it likely that there will be more cases of bipolar disorder in later life. Episodes can be misdiagnosed; for example a depressive mood swing presenting with withdrawal or a manic one with irritability.Aetiology
The phenomenon of conversion to bipolarity after many years of unipolar depression has led to speculation that cerebral organic factors may play a part in the aetiology of late-onset mania. In support of this, cognitive function is signiﬁ  cantly impaired in 
between a ﬁ  fth and a third of elderly manics.

(33,34)  Furthermore 
studies(35) have shown a high rate of neurological disturbance, 
cerebral deep white matter lesions, and reduced heritability in late-life mania.
The term ‘secondary mania’ denotes manic illness which starts 
without a prior history of affective disorder in close temporal rela-tionship to a physical illness or drug treatment and often in the absence of a family history of affective illness. A large number of conditions have been associated with secondary mania, including stroke, head injury, tumours, and non-speciﬁ  c lesions to the right 
side of the brain.
The prognosis for mania is similar to that for late-life depression; that is, there is an 80 to 90 per cent recovery in the acute phase but relapses and/or recurrences occur over time in about 50 per cent of cases.
(35)
Treatment

(35)
Treatment
As with younger patients, the mainstays of acute treatment are neuroleptics and mood stabilizers which include lithium and anticonvulsants, with ECT reserved for refractory cases. Increasingly atypical antipsychotics are used. These include olanzapine, risperi-done, and quetiapine with aripiprazole as a possible new contender. Valproate preparations are the most widely used anticonvulsant in bipolar disorder.
Some general points to consider are: (1) a greater inter-individual 
variability in drug metabolism, which makes predicting the therapeutic dose difﬁ  cult. Emergency rapid tranquillization with 
haloperidol 5 to 10 mg (often with 1 to 2 mg of lorazepam) can be used, but haloperidol has a long half-life and may lead to sudden immobility after a few days; (2) balancing risks caused by overac-tivity and exhaustion against an increased risk of falls in the elderly when using sedative tranquillizers; (3) an increased risk of confu-

sion and delirium if anticholinergic drugs are given to counteract 
side effects; and (4) the higher risk of side effects and toxicity from lithium in older patients (including a risk even at what are consid-ered therapeutic doses in younger patient).
(35) The optimal treat-
ment dose of lithium is not known. NICE recommends levels of 0.6 to 0.8 mmol/L for adults requiring maintenance lithium. Some old age psychiatrists use lower dosages but the evidence for low dose treatment in older patients is mixed.
The NICE Bipolar Guidance also covers the treatment of bipolar 
depression. The main message is that antidepressants, if used, should be combined with a mood stabilizer or an antipsychotic because of the risk of a manic switch.
Given the high rate of relapse or recurrence, prophylaxis should be considered in all patients. There has been a steady shift away from lithium to valproate over recent years, although some argue this has occurred ahead of evidence.

(36) Also, there is some evidence 
that lithium may reduce the risk of suicide in bipolar disorder as

1557
well as being neuroprotective, possibly reducing the risk of dementia 
which some population studies have been shown to be raised in affective disorder.
(31)
CRUSE Bereavement Centre (helpline@crusebereavementcare.org.uk, 0870
167 1677).
Bipolar Organisation (formerly the Manic Depressive Fellowship, http://
www.mdf.org.uk/; telephone 08456 340 540 [UK Only]; 0044 207 793 
2600 [Rest of world]).
MIND National Association for Mental Health, http://www.mind.org.uk.
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22. Nelson, J.C., Wohlreich, M.M., and Mallinckrodt, C.H. (2005). 
Duloxetine for the treatment of major depressive disorder in older patients. The American Journal of Geriatric Psychiatry ,13,
227–35.
23. Sackeim, H.A., Roose, S.P ., and Burt, T. (2005). Optimal length 
of antidepressant trials in late-life depression. Journal of Clinical 
Psychopharmacology ,25, S34–7.
24. Old Age Depression Interest Group. (1993). How long should the

24. Old Age Depression Interest Group. (1993). How long should the 
elderly take antidepressants? A double blind placebo-controlled study of continuation/prophylaxis therapy with dothiepin. The British 
Journal of Psychiatry ,162, 175–82.
25. Reynolds, C.F. III, Dew, M.A., Pollock, B.G., et al. (2006). Maintenance 
treatment of major depression in old age. The New England Journal 
of Medicine ,354, 1130–8.
26. Flint, A.J. and Rifat, S.L. (1996). The effect of sequential antidepressant 
treatment on geriatric depression. Journal of Affective Disorders ,
36, 95–105.
27. Reynolds, C.F. III, Frank, E., Perel, J.M., et al. (1999). Nortriptyline 
and interpersonal psychotherapy as maintenance therapies for 
recurrent major depression: a randomized controlled trial in patients older than 59 year. The Journal of the American Medical Association ,
281, 39–45.

28. Cole, M.G. and Dendukuri, N. (2003). Risk factors for elderly 
community subjects: a systematic review and meta-analysis . The 
American Journal of Psychiatry ,160, 1147–56 .
29. Klysner, R., Bent-Hansen, J., Hansen, H.L., et al. (2002). Efﬁ  cacy 
of citalopram in the prevention of recurrent depression in elderly 
patients: placebo-controlled study of maintenance therapy. The British 
Journal of Psychiatry ,181, 29–35.
30. Alexopoulos, G.S., Katz, I.R., Reynolds, C.F., et al. (2001). The expert 
consensus guideline series: pharmacotherapy of depressive disorders in older patients Postgrad Med Special Report ; (October):1–86, Expert 
Knowledge Systems, L.L.C, McGraw-Hill Healthcare Information 
Programs, Minneapolis, US.
31. Goodwin, G.M. (2003). For the consensus group of the British

31. Goodwin, G.M. (2003). For the consensus group of the British 
association for psychopharmacology. Evidence-based guidelines for treating bipolar disorder: recommendations from the British association for psychopharmacology. Journal of Psychopharmacology ,
17, 149–73.
32. National Institute for Health and Clinical Excellence. (2006). NICE
clinical guideline 38 bipolar disorder: the management of bipolar disorder in adults, children and adolescents, in primary and secondary care . National Institute for Health and Clinical Excellence, 
London, UK.
33. Broadhead, J. and Jacoby, R. (1990). Mania in old age: a ﬁ  rst prospective 
study. International Journal of Geriatric Psychiatry ,5, 215–22.
34. Stone, K. (1989). Mania in the elderly. The British Journal of Psychiatry ,
155, 220–4.8.5.4 mood disorders in the elderly

SECTION 8  the psychiatry of old age 1558
35. Shulman, K. (1996). Recent developments in the epidemiology, 
co-morbidity and outcome of mania old age. Reviews in Clinical 
Gerontology ,6, 249–54.
36. Shulman, K.L., Rochon, P ., and Sykora, K. (2003) Changing 
prescription patterns for lithium and valproic acid in old age: shifting practice without evidence. s, 326, 960–1.
8.5.5 Stress-related, anxiety, 
and obsessional disorders in elderly people
Stress-related, anxiety, and obsessional disorders in elderly people 
are common, distressing, costly to services, and potentially treatable. However, despite their clinical importance, many patients still go untreated, or are treated inappropriately. The speciﬁ  c conditions 
covered here are described in detail elsewhere; this chapter focuses on the differences and difﬁ  culties that are encountered when they 
occur in old age.
The ICD-10 and DSM-IV diagnostic classiﬁ  cations are described

The ICD-10 and DSM-IV diagnostic classiﬁ  cations are described 
in Chapter 1.11. Although the term ‘neurotic disorder’ is not used in DSM-IV , it is retained in ICD-10 as a collective term for the dis-orders considered in this chapter. The extensive comorbidity between these conditions and their diagnostic instability over time are also apparent in elderly people, which supports the idea that they are better considered as aspects of a general neurotic syndrome than as discrete diagnostic categories.
(1) This model is particularly 
applicable to elderly patients, whose illnesses are often the result of a long interaction between individual vulnerability, circumstances, and maladaptive responses to distress. Obsessive–compulsive dis-order (OCD) is probably not part of a general neurotic syndrome. Although classiﬁ  ed with the anxiety disorders in ICD-10 and

DSM-IV , it has a number of features that suggest it is a distinct and stable condition with a different aetiology (see Chapter 4.8).
These disorders have psychological, somatic, and behavioural features. In elderly people, these symptoms and behaviours are simi-lar to those seen in younger patients, but there are some important differences in how they manifest themselves or are perceived by others. Although most neurotic disorders in elderly patients are long standing, an important minority of cases have their onset in old age, and it is these that usually cause the greatest diagnostic difﬁ  culties.
Psychological symptoms
Symptoms of anxiety and depression occur to some extent in 
all of these disorders in late life. Depressive symptomatology in old age is described elsewhere (see Chapter 8.5.4). Regarding anxiety, the focus of the worries and fears of elderly people is on those issues that are of general concern in this age group (health, ﬁ  nances,

crime). The phobias described by elderly people are similar to those seen in younger adults,
(2) although some, such as the fear of 
falling, are more commonly seen in old age. Clinically signiﬁ  cant 
anxieties and fears in elderly people are often dismissed as reason-able purely on grounds of age. In fact, it is physical frailty and the availability of social support that determine elderly people’s perceptions of vulnerability and risk, and these rather than age should be considered when deciding whether or not concerns are reasonable.
The clinical features of OCD in old age are similar to those seen 
in younger patients. Obsessional symptoms rarely appear for the ﬁ rst time after the age of 50 years, and in such cases the possibility 
of an organic cause such as dementia or a space-occupying lesion should be investigated. They may also form part of a primary affective disorder.
Somatic symptoms

The somatic symptoms of anxiety are similar at all ages, but in elderly patients there is a greater likelihood of misdiagnosis and inappropriate investigation and treatment. This is particularly true of elderly patients experiencing panic attacks, who tend to be mis-directed to cardiologists, neurologists, and gastroenterologists.

The psychological and somatic symptoms of anxiety have several adverse behavioural consequences, for example, phobic avoidance, the abuse of sedative drugs and alcohol, and the development of troublesome abnormal illness behaviours such as somatization and hypochondriasis. In elderly patients these behaviours are usually of long standing, but they can develop following the onset of anxiety or depression in old age. In cognitively impaired patients, disturbed behaviour may be the main presenting feature.
In old age, these disorders usually present in primary care and the general hospital, and clinicians working in these settings need to be able to identify them, and to distinguish them from the other men tal 
and physical disorders that they may accompany or mimic.

There is extensive comorbidity between neurotic disorders and depression, and depressive symptoms are an integral component of many neurotic disorders, particularly in old age. It is therefore important to assess to what extent depression forms part of the clinical picture, as this may require treatment in its own right. Depressive disorder that is comorbid with anxiety responds less well to antidepressant treatment, and there is a greater likelihood of relapse and recurrence.
Dementia
In the early stages, dementia may present with symptoms such as anxiety, and obsessionality. More commonly, anxiety and depres-sion cause subjective cognitive impairment, which may be the presenting symptom. Dementia is associated with higher rates of anxiety, unrelated to severity of cognitive impairment. Patients with vascular dementia may be more vulnerable in this respect.

1559
This anxiety may be associated with the implications of the 
diagnosis in those patients who retain insight, or a response to psychotic symptoms or misinterpretations of the external environ-ment in those who are more severely affected. The caregivers of people with dementia are also vulnerable to developing depressive and anxiety disorders, particularly if they have a previous psychiatric history.
Delirium
Although delirium is a relatively quiet disorder in elderly patients (see Chapter 8.5.1), it may be associated with signiﬁ  cant affective 
disturbances, often in response to frightening visual hallucinations and imagined assaults. Conversely, in vulnerable individuals, severe anxiety may be sufﬁ  cient to precipitate delirium.
Paranoid states and schizophrenia
Patients suffering from these disorders may experience signiﬁ  cant 
fear and anxiety in response to their psychotic experiences, but this rarely causes diagnostic difﬁ  culty. Unusual hypochondriacal

fear and anxiety in response to their psychotic experiences, but this rarely causes diagnostic difﬁ  culty. Unusual hypochondriacal 
ideas may sometimes be difficult to distinguish from mono-symptomatic delusional disorders.
There is an important association between physical illness and neurotic disorders in old age. As a life event, an episode of physical illness may be the cause of neurotic disorder, particularly if it is severe or has sinister implications. For example, mild anxiety symp-toms are common following myocardial infarction in old age, and vulnerable individuals may develop a disabling ‘cardiac neurosis’ focused on their somatic anxiety symptoms. Most cases of agora-phobia that develop after the age of 65 years are not induced by panic but arise following an alarming experience of physical ill health.
(1) Follow-up studies of stroke survivors show that condi-

tions such as agoraphobia and generalized anxiety are common, tend to become chronic in a signiﬁ  cant proportion of cases, and 
are associated with poor functional recovery.
(3) Chronic disabilities 
that limit mobility and independence, such as arthritis, balance disorders, and sensory impairments, increase the patient’s sense of personal vulnerability and are also associated with elevated rates of anxiety and secondary avoidance.
Neurotic disorders can also cause physical illness by direct or 
indirect effects on the body. In elderly people, this may come about as the result of many years of harmful anxiety-driven behaviours such as smoking and alcohol abuse.
In terms of differential diagnosis, there is also the problem that

In terms of differential diagnosis, there is also the problem that 
a wide range of physical disorders may present with neurotic symptoms, and vice versa. In particular, a number of important cardiovascular, respiratory, and endocrine disorders may present with anxiety or depression and little else in old age.
(4) Anxiety 
symptoms may also be caused by prescribed drugs such as oral hypoglycaemics and corticosteroids, or by excessive intake of caf-feine and preparations containing sympathomimetics. In view of this, the clinical assessment should always include a drug history and a physical examination. A physical cause for neurotic symp-toms should be considered if there is no past psychiatric history and no life event or other circumstances to account for their 
onset.Epidemiology
While neurotic disorders are relatively uncommon in clinical 
populations, there are signiﬁ  cant prevalence rates in community 
samples, indicating that they do not pass easily through the ﬁ  lters

samples, indicating that they do not pass easily through the ﬁ  lters 
on the pathway to care. Surveys using different diagnostic criteria produce different rates of disorder, which makes comparisons difﬁ cult. However, some general ﬁ  ndings include a female prepon-
derance for most disorders, and a fall in prevalence and incidence rates with age. Most elderly people with neurotic disorders devel-oped them before their ﬁ  fties, but elderly cases of phobic disorder, 
panic, and OCD tend to be of later onset.
(5, 6)
Aetiology
The acquisition and subsequent loss or elaboration of the symptoms of anxiety and depression are determined by the patient’s premorbid vulnerability, the particular factors that precipitate the episode of illness (destabilization), and the measures taken by the patient or the doctor to control it (restitution).
(7)

(7)
Most of the evidence that biological factors play a role in the development of neurotic disorders derives from studies in younger subjects (see Chapters 4.7.1–4.7.3). These studies indicate that genetic factors contribute signiﬁ  cantly to premorbid vulnerability, 
but the role that they play in old age is not known. Neuroimaging studies of elderly depressed patients provide only limited informa-tion about neurotic disorders, suggesting that patients with milder forms of depression and higher anxiety scores are more likely than severely depressed patients to have normal CT scans. It has been suggested that some anxiety disorders following stroke may be related to lesion location.
(8)
(a) Social adversity

(8)
This may have its effect through higher rates of physical illness and exposure to adverse life events, or by inculcating a sense of poor self-esteem. However, the impact of adversity on self-esteem in old age is not clear, since a hard life may in fact equip one to cope better with the difﬁ  culties of old age.
(b) Life events
Adverse life events have an important role in determining the 
onset of depressive and anxiety disorders (see Chapters 4.5.5.1 and 4.7.1–4.7.3). It is the meaning of the event to the individual that is important; loss events lead to depression and threatening events to anxiety. Some types of life events (physical illness, bereavement, retirement, institutionalization) are more common in old age, and are associated with psychiatric morbidity in vulnerable individuals.
Extreme trauma and catastrophe are well known to have adverse

Extreme trauma and catastrophe are well known to have adverse 
psychological consequences, and post-traumatic stress disorder (PTSD) is a recognized diagnosis in ICD-10 and DSM-IV (see Chapter 4.6.2). It is clear from studies of elderly survivors of traumatic experiences such as war and the holocaust that PTSD is often a persistent disorder, and that its onset or recurrence may be precipitated by events many years after the original traumatic 8.5.5 stress-related, anxiety, and obsessional disorders in elderly people

SECTION 8  the psychiatry of old age 1560
experience. PTSD may also develop following trauma in late life, 
and as in younger subjects it tends to persist.
(c) Early experience
Early parental loss and childhood physical and sexual abuse are associated with the development of mental disorder in adult life, an effect that persists into old age.
(1)
(d) Relationships
There is evidence that both the quantity and quality of social rela-tionships are important determinants of psychological well-being in old age, and that factors such as smaller social networks are asso-ciated with anxiety disorders.
(9)
The limited evidence suggests that neurotic disorders in elderly people tend to become chronic and that older age of onset is a predictor of poor outcome, particularly in men.
(10) The pattern of 
symptoms may change over time.(11) Elderly patients with anxiety 
disorders have an excess mortality.
Treatment
Evidence

Treatment
Evidence
There is little high-quality evidence available about the effects of treatments for these disorders in elderly patients. Cognitive behaviour therapy (CBT) is of proven beneﬁ  t in younger adults 
(see Chapter 6.3.2.1), and there is some evidence that it is also effective in later life.
(12) There have been surprisingly few trials 
of anxiolytic drugs in elderly patients, but there is evidence that antidepressant drugs such as SSRIs and venlafaxine are effective in the treatment of generalized anxiety. In the absence of good evidence for a particular treatment, patient preference, and choice are important considerations.

Since most patients are seen in primary care and general medical settings, this is where the focus of management should be. The role of specialist old age psychiatry services should be to provide any advice and support that is necessary, which may include assuming responsibility for the most complex cases. Wherever the patient is seen and treated, the following should need consideration from the outset (see also Chapter 8.6):
◆ a thorough assessment and accurate diagnosis as the basis for the management plan
◆ the full range of physical and psychological treatment options, including patient education, lifestyle advice, bibliotherapy, and supportive counselling
◆ clear goals for the treatment plan, agreed if possible with the patient
◆ an adequate trial of treatment
◆ the likely duration of treatment
◆ frequency of review
◆ any possible adverse consequences, such as dependency, adverse side effects, risk of self-harm.(a) Psychological treatments

For the most part, the goals and techniques of CBT are the same for elderly patients as they are for younger adults (see Chapter 6.3.2.1). However, these may require some adaptation to accommodate sensory impairments, physical illness and disability, and cognitive dysfunction.
(13) The need to tailor treatment to the individual may 
limit the value of CBT in a group setting, although this has to be set against the beneﬁ  ts of shared experience and peer support. Group 
treatment is probably more straightforward with task-centred activities such as anxiety management.
The use of formal psychodynamic approaches to management is

The use of formal psychodynamic approaches to management is 
currently limited by economic constraints, and the lack of evidence regarding their effectiveness. However, health professionals should have some knowledge of the psychodynamics that underlie the concerns of elderly patients, and the mental defences that they use. They also need to be aware of their own preconceptions and cognitive distortions regarding the experience of old age, the psychological sophistication of elderly people, and their capacity for growth and change.
(b) Physical treatments
Chapter 8.6 describes the general principles of drug treatment in old age. None of the drugs used to treat anxiety in elderly people is entirely without problems, so they should be prescribed with care.
(14) Benzodiazepines are the most commonly used drugs, but

(14) Benzodiazepines are the most commonly used drugs, but 
they are often prescribed inappropriately. Elderly patients are par-ticularly sensitive to their adverse effects, and drug accumulation may lead to delirium, incontinence, and falls. Compounds with short half-lives and no active metabolites, such as oxazepam, are least problematic, although patients may develop withdrawal symptoms if they are discontinued, or taken erratically. Long-term benzodiazepine use should be avoided where possible, although it may be necessary in a few patients unresponsive to other forms of treatment.
Antidepressant drugs are now the ﬁ  rst choice in generalized anx-
iety and panic, particularly if depressive symptoms are prominent. The use of antidepressants in elderly patients is discussed in Chapter 8.5.4. SSRIs also have a speciﬁ  c effect in OCD. Neuroleptics 
have only a limited role in the management of anxiety, given their

have only a limited role in the management of anxiety, given their 
potentially disabling extrapyramidal side effects. However, a short course of low-dose treatment with a drug such as haloperidol or zuclopenthixol may be considered in those unable to tolerate benzodiazepines. Alternatively, sedative antihistamine drugs such as hydroxyzine may be useful. β-blockers are used in younger adults 
to control the sympathetic somatic anxiety symptoms, but contra-indications such as chronic obstructive airways disease, sinus bradycardia, and heart failure limit their use in elderly patients. Buspirone is an azapirone anxiolytic that is well tolerated by elderly patients, but it takes about 2 weeks to become effective, so is not useful for the management of acute episodes. It is indicated for severe chronic generalized anxiety and in patients where there is risk of dependence or abuse.

The possibilities for primary prevention are limited at present. However, in view of the association with physical illness, there may be an opportunity to intervene and prevent the development of chronic neurotic disability following strokes, heart attacks, and

1561
falls. It remains to be seen if the improved management of these 
disorders earlier in life will result in lower rates of chronicity and recurrence as cohorts age.
Lindesay, J. (ed.) (1995). Neurotic disorders in the elderly . Oxford University 
Lindesay, J. (2008). Neurotic disorders. In The Oxford textbook of old age 
psychiatry  (eds. R. Jacoby, T. Dening, A. Thomas, and C. Oppenheimer). 
National Institute for Clinical Excellence. (2004). Anxiety: management 
of anxiety (panic disorder with or without agoraphobia and generalised anxiety disorder) in adults in primary, secondary and community care . Clinical Guideline 22. NICE, London (www.nice.org.uk/
CG022NICEguideline).
Ruskin, P .E. and Talbot, J.A. (eds.) (1996). Aging and posttraumatic stress 
disorder . American Psychiatric Press, Washington, DC.
Salzman, C. and Lebowitz, B. (eds.) (1991). Anxiety in the elderly . Springer, 
New Y ork.

New Y ork.
 1. Tyrer, P . (1989). Classiﬁ  cation of neurosis . Wiley, Chichester.
 2. Lindesay, J. (1991). Phobic disorders in the elderly. The British Journal 
of Psychiatry ,159, 531–41.
 3. Astrom, M. (1996). Generalized anxiety disorder in stroke patients. 
A 3-year longitudinal study. Stroke ,27, 270–5.
 4. Pitt, B. (1995). Neurotic disorders and physical illness. In Neurotic 
disorders in the elderly  (ed. J. Lindesay), pp. 46–55. Oxford University 
 5. Robins, L. and Regier, D. (eds.) (1991). Psychiatric disorders in America .
Free Press, New Y ork.
 6. Krasucki, C., Howard, R., and Mann, A. (1998). The relationship 
between anxiety disorders and age. International Journal of Geriatric 
Psychiatry ,13, 79–99.
 7. Goldberg, D. and Huxley, P . (1992). Common mental disorders: a

 7. Goldberg, D. and Huxley, P . (1992). Common mental disorders: a 
bio-social model . Tavistock/Routledge, London.
 8. Robinson, R.G. (1998). The clinical neuropsychiatry of stroke .
 9. Beekman, A.T.F., Bremmer, M.A., Deeg, D.J.H., et al. (1998). Anxiety 
disorders in later life: a report from the longitudinal aging study Amsterdam. International Journal of Geriatric Psychiatry ,13,
717–26.
10. Noyes, R. and Clancy, J. (1976). Anxiety neurosis: a 5-year follow-up. 
The Journal of Nervous and Mental Disease ,162, 200–5.
11. Larkin, A.B., Copeland, J.R.M., Dewey, M.E., et al. (1992). The 
natural history of neurotic disorder in an elderly urban population. Findings from the Liverpool longitudinal study of continuing health in the community. The British Journal of Psychiatry ,160,
681–6.

681–6.
12. Mohlman, J. (2004). Psychosocial treatment of late-life generalized 
anxiety disorder: current status and future directions. Clinical
Psychology Review ,24, 149–69.
13. Koder, D.A. (1998). Treatment of anxiety in the cognitively 
impaired elderly: can cognitive-behavior therapy help? International 
Psychogeriatrics ,10, 173–82.
14. Suribhatla, S. and Lindesay, J. (2005). Treatment of anxiety disorders. 
In Practical old age psychopharmacology , Chap. 10 (eds. S. Curran and 
R. Bullock). Radcliffe, Abingdon.8.5.6 Personality disorders 
in the elderly
The study of personality disorder (PD) in late life presents concep-
tual, diagnostic, and methodological difﬁ  culties. By deﬁ  nition, PD 
is considered a group of personality traits that relatively persistent through adulthood. However, the concept of PD persisting throughout the lifespan contradicts widespread clinical belief that they become less severe with ageing. For example, DSM-IV

(1) notes 
that ‘some types of personality disorders . . . tend to become less evident or remit with age’ .
There are difﬁ  culties in studying PD in the elderly. One is the 
instability of the deﬁ  nition of PD over time, making it difﬁ  cult to 
relate earlier studies to those using current deﬁ  nitions of PD. 
In addition, diagnostic criteria are subject to criticism when applied to the elderly, in that they may be ‘age-biased’ .
(2, 3) Finally, the meth-
odology used to diagnose PD has been highly variable and difﬁ  cult 
to interpret between studies.
A major issue is whether personality is fully developed by early 
adulthood and then remains unchanged, or whether personality continues to develop and change throughout life. The work of McCrae and Costa
(4) demonstrated that personality characteristics

(4) demonstrated that personality characteristics 
are relatively stable within individuals over a 30-year period with correlations ranging from 0.7 to 0.8. However, this also demon-strates that complete stability is not there and suggests certain aspects of the personality may still develop and change with ageing. This suggests that PD may also change over the lifespan.
Another issue is whether underlying traits that persist through-
out the lifespan can rise to the level of a PD depending on the environment. For example, traits that may be personality disor-dered in young adult life, such as extreme dependency, may be an appropriate and adaptive trait for an older individual with multiple physical disabilities.
(5) Conversely, an individual may have a trait of 
extreme independence that may be adaptive in earlier life but which

extreme independence that may be adaptive in earlier life but which 
leads to distress and maladaptive functioning in a setting requiring dependence, such as a nursing home. Thus it is possible to have a 
PD diagnosed for the ﬁ  rst time in late life, which goes against the 
very deﬁ  nition of lifelong PD.
Clinical features of PD and details of their classification are 
reviewed in Chapters 4.12.2 and 4.12.3. However, there is difﬁ  culty 
in simply relating these criteria, which were developed for younger individuals, to the elderly. Typical diagnostic behaviours that clinicians associate with PD in younger adults may present as dif-
ferent behaviours in the elderly. This may lead clinicians to over-
look personality traits and disorders in older individuals. For 
example, a criterion of antisocial personality disorder is the repeated

example, a criterion of antisocial personality disorder is the repeated 
failure to sustain consistent work, behaviour not applicable to the older retired individual. Y et it is possible that the personality 
trait of irresponsibility, which led to the loss of jobs earlier in life continues, now appearing as a behaviour such as medicine non-compliance. Some authors have thus argued that the clinical 8.5.6 personality disorders in the elderly

SECTION 8  the psychiatry of old age 1562
features for some PD are age-biased since certain behaviours are 
less likely to occur in elderly persons despite the persistence of personality traits.
(2, 3)
Diagnosis of personality disorders
Diagnostic criteria for PD are discussed in Chapter 4.12.3. Because features of PD may change with ageing, diagnosis can be difﬁ  cult. 
Overlap with Axis I diagnoses such as depression or dementia make the diagnosis even more challenging. For example, depressed elderly people have symptoms normally associated with PD as they may be more dependent, avoidant, resistant, negative, and somatic.
(6)
In addition, depressed elderly people may view their lives negatively and overestimate personality psychopathology.
(7, 8)
Clinicians may be reticent to give a personality diagnosis to an 
individual with multiple medical problems to which maladaptive behaviours may be attributed even if a lifelong history of personal-ity pathology is established.

(8) They may also be concerned about 
the validity of historical information needed to make a PD diagno-sis. Therefore, in making a diagnosis of PD, a clinician should take a thorough history from as many reliable outside informants as possible. If the patient is in a state of acute distress with a current Axis I diagnosis such as depression, it is best to defer diagnosis of the PD until the illness is in remission. Otherwise, it is especially important to ask outside informants to think back to when the individual was a younger person, as current symptoms can colour the perception of lifelong personality traits. Asking for speciﬁ  c 
examples of history such as, details of relationships and job history, legal history, and the like, will be more helpful than just general descriptions of personality.

If behavioural difﬁ  culties and personality problems are found 
to be recent, the clinician needs to search carefully for a superim-posed medical condition, or a psychiatric condition such as depression. Clinicians should carefully screen for illnesses such as dementia, stroke, or other neurological disease, or a systemic medi-cal illness. Those with frontal lobe dementia, Alzheimer’s disease, or vascular dementia may have personality changes early in their life course.
(9–11)
Epidemiology and aetiology
The prevalence of PD in the elderly varies as to the methodology used and the population studied. It should be noted that no assess-ment instrument for PD in the elderly has been validated.
Community studies
Community studies have been the most useful to date. A community study,

(12) using the Epidemiologic Catchment Area ( ECA ) data, 
had 841 subjects examined by psychiatrists using the semi-structured Standardized Psychiatric Examination with DSM-III criteria. Comparing those over the age of 55 with those under 55, older individuals were found signiﬁ  cantly less likely to have a PD (6.6 
to 10.5 per cent) as compared with younger individuals. This ﬁ  nd-
ing was almost entirely due to a three-fold higher prevalence of 
cluster B PD in those under the age of 55, especially antisocial and 
histrionic PD. Interestingly, in this study none of the older indi-viduals were found to have cluster A PD. Table 8.5.6.1 summarizes the ﬁ  ndings of this large community study. The strengths of this 
study were that it was a community rather than a clinical sample, and subjects were evaluated by psychiatrists using a structured

study were that it was a community rather than a clinical sample, and subjects were evaluated by psychiatrists using a structured 
questionnaire. Limitations of this study were those inherent to the study of PD in late life, in that older subjects may have been inac-curate in recalling maladaptive behaviours, outside informants were not used, and lack of non-validated instruments for diagnos-ing PD in the elderly.
A community study of 43 093 persons, examining alcohol and 
related conditions across the life span, conﬁ  rmed that those over 
65 years had signiﬁ  cantly lower rates of all studied PD including 
avoidant, obsessive–compulsive, paranoid, schizoid, histrionic, and 
antisocial, using DSM-IV criteria.
(13)
A community survey study of DSM-III PD traits using the

(13)
A community survey study of DSM-III PD traits using the 
Personality Diagnostic Questionnaire revealed that ‘dramatic’ and ‘anxious’ personality traits declined up to 60 years of age with a slight increase thereafter, but that ‘odd’ or ‘eccentric’ traits showed no change with age.
(14)
Psychiatric populations
In addition to community samples, speciﬁ  c clinical samples have 
been examined. Limitations of these studies are the possibility of over diagnosis of PD due to symptoms of Axis I diagnoses.
A retrospective study of 2322 psychiatric inpatients with 
major depression found the prevalence of PD to be 11.2 per cent in those over the age of 65 as compared with 17.2 per cent for those under 65.
(15)
Psychiatric inpatient studies suffer from the limitation of diag-

(15)
nosing PD in the face of an acute psychiatric illness requiring hos-pitalization, making them likely to overdiagnose. Such studies are of very limited value.
(16,17)
Unfortunately, outpatient studies have similar limitations when 
examining those with concurrent Axis I diagnoses. A study of 36 psychiatric outpatients, including those with bipolar disorder, delusional disorder, and schizophrenia, revealed that 58 per cent had a diagnosis of personality disorder.
(18) Arguably, diagnosing Table 8.5.6.1  Weighted prevalence (%) of DSM-III personality 
disorders in a large community study
Age < 55 years Age > 55 years
Cluster A 0.1 0.0
Paranoid 0.0 0.0Schizoid 0.1 0.0Schizotypal 0.1 0.0
Cluster B 6.8 2.2*
Antisocial 2.7 0.1*
Borderline 0.8 0.0Histrionic 4.3 2.2*Narcissistic 0.0 0.0
Cluster C 3.8 4.3
Avoidant 0.0 0.0Dependent 0.2 0.1Obsessive–compulsive 3.6 3.3Passive-aggressive 0.0 1.0

Any personality disorder 10.5 6.6*
* p<0.05
Reproduced from B.J. Cohen et al. (1994). Personality disorders in later life. A community 
study. British Journal of Psychiatry , 165, 493–9, copyright 1994, The Royal College of 
Psychiatrists.

1563
personality disorder in the face of these disorders is likely to be 
difﬁ cult and result in an overestimation.
Prevalence summary
A meta-analysis of 11 articles published from 1980 to 1994 of per-
sonality disorders based on DSM-III or DSM-IIIR criteria revealed an approximately 10 per cent prevalence of personality disorders in those aged 50 and over.
(19) In comparing these studies it was noted 
that the method of diagnosis affected the prevalence of personality disorder. In conclusion, the authors felt that there was a deﬁ  nite 
need for well-designed studies using statistically robust samples to assess the true prevalence of personality disorders in late life.
Taking the best studies together—the ECA community study 
and the meta-analysis—the prevalence of personality disorder in the elderly, as currently deﬁ  ned, ranges from 7 to 10 per cent, with 
a decrease in prevalence of cluster B diagnoses.

Longitudinal community studies of PD have not been performed. With longitudinal data lacking, only cross-sectional studies are available. However, cross-sectional studies have a variety of limitations, including the possibility of a cohort effect explaining changes in prevalence in late life.
Antisocial personality disorder has been the best studied. The 
ECA study revealed that antisocial personality disorder declined from a 1-month prevalence of 0.9 per cent for individuals between 25 and 44 years of age to 0 per cent for those over the age of 65. When considering men only, the rate fell from 1.5 per cent in those aged 22 to 44 to 0.1 per cent in those over 65.
(20) Supporting this is 
a study revealing the decline in lifetime prevalence in antisocial personality disorder from between 2.1 and 3.3 per cent to between 0.2 and 0.8 per cent in those aged 65 and older.
(21) In addition,

(21) In addition, 
antisocial traits, as measured by the Minnesota Multiphasic Personality Index, reveal a decline with ageing.
(22) However, a 
forensic centre study revealed while antisocial PD declined after the age of 27, one-third remained criminally active throughout their lives.
(23)
Several hypotheses exist to explain this apparent decline in anti-
social personality disorder with ageing. Personality may continue to mature and develop. Early death due to high-risk behaviour or a change in antisocial behaviours to other symptoms including hyperchondriasis, depression, or alcoholism may occur.
(23) Also, 
behaviours such as criminality may decrease in older individuals, but antisocial personality traits remain and are simply more difﬁ  -
cult to measure using current diagnostic criteria. Also, decrease in impulsive and aggressive behaviours may correlate with full myelin-ation of frontal, temporal, and parietal cortices that does not occur until 30 or 40 years of age.

(24) Changes in brain neurochemistry 
with ageing, including serotonin and dopamine, may also result in decreased impulsiveness or aggressiveness.
(12) Decreased testoster-
one levels in men with ageing may contribute to a decline in these traits.
(25)
Other Cluster B disorders may decline with ageing. The ECA 
study previously reviewed found a decline in antisocial and histri-onic disorder.
(23) Another community study supported a decline in 
histrionic PD with ageing.(26) Interestingly, the pattern of decline 
varied with gender, with rates remaining constant in women but declining in men. Similarly, a diagnosis of borderline PD is rare in elderly individuals, with only two case reports in the literature.
(5)
There is conﬂ  icting data regarding a decline in cluster A or C diag-
noses. A large community study revealed lower rates of both Cluster A and C diagnoses in the elderly.
(13) However, a study of schizo-

typal PD revealed all cases began before 40 years of age and contin-ued lifelong.
(27)
Some work has been done on the interaction of PD with Axis I 
diagnoses. Studies of depressed elderly patients suggest PD is associ-ated with earlier age of depression onset, chronicity, and severity of dysthymia
(28,29) however depression may exacerbate or conceal per-
sonality traits, thus making ﬁ  rm conclusions of PD in such indi-
viduals difﬁ  cult. In the ECA study, certain Axis I diagnoses were 
found to be more common with a PD diagnosis. For example, all cases of obsessive–compulsive disorder in older individuals occurred concurrent with a PD.
(12) Both generalized anxiety disorder and sub-

stance use disorders were more common in the presence of a PD. There were no differences in the prevalence of schizophrenia and major depression in those with or without a PD. The ﬁ  ndings need 
to be conﬁ  rmed since the group of elderly with PD was small.
A recent interesting study has revealed any PD (DSM-IV criteria) 
is associated with increased risk of stroke and ischemic heart disease, adding to the possible morbidity of these disorders.
(30) However, 
such results should be viewed w ith caution as no screening was done 
to rule out depression or other associated factors that are prevalent in this population and may have led to over diagnosis of PD.

Given the relative lack of data regarding PD in the elderly, it is not surprising there is a corresponding lack of information regarding treatment and management. In general, clinicians should have a low threshold for suspecting concurrent psychiatric diagnosis, as major depression, anxiety, substance use disorders or dementia may mimic or exacerbate a personality disorder.
(5) Physical and 
medical problems should be thoroughly evaluated and treated to minimize any associated complaints.
Social and family supports should be explored and maximized. 
Firm and consistent limits must be set by the clinician for both patients and their families in regard to inappropriate behaviour.
(5)

(5)
Clinicians should also try to determine why the disordered behav-iour is occurring at a particular time. For example, placement in a nursing home may be stressful to an individual who has had difﬁ culty forming relationships and is now dependent on a group 
of caregivers. Psychotherapy with the goal of focusing on current life stresses, the individual’s vulnerabilities, and adaptive strategies can help the patient adjust to the current circumstance.
(5)
Psychotherapeutic treatments used for personality disorders in

(5)
Psychotherapeutic treatments used for personality disorders in 
younger individuals may be tried although little data exists on their effectiveness for elderly. A study of Dialectical Behavior Therapy (DBT) used in combination with medication to treat elderly depressives with personality disorders revealed better results than just medication. The study is limited in that such results are com-mon in other studies using any psychotherapy with medication versus medication alone and does not support a speciﬁ  c usefulness 
of DBT in elderly personality disorder. However, the study is the ﬁ rst to use DBT in an older population and shows it is tolerable in 
this age group.
If possible, psychiatric medication should be avoided unless there 
is a speciﬁ  c diagnosed condition. This will minimize the possibility 8.5.6 personality disorders in the elderly

SECTION 8  the psychiatry of old age 1564
of side effects in elderly individuals and avoid dependency and 
control issues.(5) This is important as elderly individuals with 
abnormal personality traits have been found to be at higher risk of receiving psychotropic medication.
(31)
There are no data available for preventing the development of a PD in late life. Clearly, more information is needed on the longitudinal course of diagnosed PD in late life so that information regarding treatment and prevention may be realized.
At the time of writing, there are no books or reports that give an overview 
of personality disorder in the elderly. Further information about speciﬁ  c aspects of the subject can be obtained from the relevant 
references in the text.
manual of mental disorder  (4th edn). American Psychiatric Association, 

 2. Agronin, M.E. and Maletta, G. (2000). Personality disorders in late 
life: understanding and overcoming the gap in research. The American 
Journal of Geriatric Psychiatry ,8, 4–18.
 3. Kroessler, D. (1990). Personality disorder in the elderly. Hospital & 
Community Psychiatry ,41, 1325–9.
 4. McCrae, R.R. and Costa, P .T. (1984). Emerging lives, enduring 
dispositions . Little Brown, Boston, MA.
 5. Holroyd, S. and Rabins, P .V . (1994). Personality disorders. In Principles 
of geriatric medicine and gerontology  (3rd edn) (eds. W.R. Hazzard, 
E.L. Bierman, J.P . Blass, W.H. Ettinger, and J.B. Hatter), pp. 1131–6. 
McGraw–Hill, NY.
 6. Thompson, L.W., Gallagher, D., and Czirr, R. (1988). Personality

 6. Thompson, L.W., Gallagher, D., and Czirr, R. (1988). Personality 
disorder and outcome in the treatment of late-life depression. Journal of Geriatric Psychiatry ,21, 133–46.
 7. Hirschfeld, R.M.A., Klerman, G.L., and Clayton, P .J. (1983). Assessing 
personality: effects of the depressive state on trait measurement. The American Journal of Psychiatry ,140, 695–9.
 8. Reich, J., Noyes, R., Hirschfeld, R.M.A., et al. (1987). State and 
personality in depressed and manic patients. The American Journal of 
Psychiatry ,144, 181–7.
 9. Petry, S., Cummings, J.L., and Hill, M.A. (1990). Personality alterations 
in dementia of the Alzheimer type. Archives of Neurology ,45, 1187–90.
10. Neary, D., Snowden, J., and Mann, D. (2005). Frontotemporal 
11. Dian, L., Cummings, J.L., Petry, S., et al. (1990). Personality alterations

11. Dian, L., Cummings, J.L., Petry, S., et al. (1990). Personality alterations 
in multi–infarct dementia. Psychosomatics ,31, 415–19.
12. Cohen, B.J., Nestadt, G., Samuels, J.F., et al. (1994). Personality 
disorders in later life. A community study. The British Journal 
of Psychiatry ,165, 493–9.
13. Grant, B.F., Hasin, D.S., Stinson, F.S., et al. (2004). Prevalence, 
correlates and disability of personality disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. The Journal of Clinical Psychiatry ,65, 948–58.
14. Reich, J., Nduaguba, M., and Y ates, W. (1988). Age and sex distribution 
of DSM–III personality cluster traits in a community population. Comprehensive Psychiatry ,29, 298–303.
15. Fogel, B.S. and Westlake, R. (1990). Personality disorder diagnoses

15. Fogel, B.S. and Westlake, R. (1990). Personality disorder diagnoses 
and age in inpatients with major depression. The Journal of Clinical 
Psychiatry ,51, 232–5.16. Molinari, V . (1993). Personality disorders and relapse rates among 
geropsychiatric inpatients. Clinical Gerontologist ,14, 49–52.
17. Molinari, V ., Ames, A., and Essa, M. (1994). Prevalence of personality 
disorders in two geropsychiatric inpatient units. Journal of Geriatric 
Psychiatry and Neurology ,7, 209–15.
18. Molinari, V . and Marmion, J. (1993). Personality disorders in 
geropsychiatric outpatients. Psychological Reports ,73, 256–8.
19. Abrams, R.C. and Horowitz, S.V . (1996). Personality disorders after age 
50: a meta–analysis. Journal of Personality Disorders ,10, 271–81.
20. Regier, D.A., Farmer, M.E., Rae, D.S., et al. (1988). One–month

20. Regier, D.A., Farmer, M.E., Rae, D.S., et al. (1988). One–month 
prevalence of mental disorders in the United States. Archives of General 
Psychiatry ,45, 977–86.
21. Robins, L.N. (1984). Lifetime prevalence of speciﬁ  c psychiatric 
disorders in three sites. Archives of General Psychiatry ,41, 949–58.
22. Weiss, J.M. (1973). The natural history of antisocial attitudes–
what happens to psychopaths? Journal of Geriatric Psychiatry ,6,
236–42.
23. Arboleda–Florez, J. and Holley, H.L. (1991). Antisocial burnout: an 
exploratory study. Bulletin of the American Academy of Psychiatry 
and the Law ,19, 173–83.
24. Elliott, F.A. (1992). Violence, the neurologic contribution: an overview. 
Archives of Neurology ,49, 595–603.
25. Gray, A., Jackson, A.N., and McKinlay, J.B. (1991). The relation between

25. Gray, A., Jackson, A.N., and McKinlay, J.B. (1991). The relation between 
dominance anger and hormones in normally aging men: results from the Massachusetts Male Aging Study. Psychosomatic Medicine ,
53, 375–85.
26. Nestadt, G., Romanoski, A.J., Chahal, R., et al. (1990). An 
epidemiologic study of histrionic personality disorder. Psychological 
Medicine ,20, 413–22.
27. Baron, M., Given, R., Asnis, L., et al. (1983). Age of onset 
in schizophrenia and schizotypal disorder. Neuropsychobiology ,
10, 199–204.
28. Abrams, R.C., Rosendahl, E., and Card, C. (1994). Personality disorder 
correlates of late and early onset depression. Journal of the American 
Geriatric Society ,42, 727–31.
29. Devanand, D.P ., Turret, N., and Moody, B.J. (2000). Personality 
disorder in elderly patients with dysthymic disorder. The American 
Journal of Geriatric Psychiatry ,8, 188–95.

30. Moran, P ., Stewart, R., Brugha, T., et al. (2007). Personality disorder 
and cardiovascular disease: results from a national household survey. 
The Journal of Clinical Psychiatry ,68, 69–74.
31. Mann, A.H. (1981). The twelve–month outcome of patients with 
neurotic illness in general practice. Psychological Medicine ,11,
535–50.
8.5.7 Suicide and deliberate 
self-harm in elderly people
Although in some countries suicide rates in young males have risen 
dramatically in the last decade or so, suicide in old age is important because rates in older people, especially those over 74, are still proportionately higher in most countries of the world where rea-sonably reliable statistics can be obtained.
(1) For example, in 2004

(1) For example, in 2004 
in Lithuania where suicide incidence is currently the highest, the

1565
overall rate in males per 100 000 total population was 70.1, but in 
men over 74 the rate was 80.2. In the United States, where suicide is neither especially common nor rare, in 2002 the overall rate for males per 100 000 total population was 17.9, but 40.7 in men over 74. Rates for older women are nearly always much lower than for their male counterparts.
A second reason for the importance of suicide in old age is that the 
proportion of older people in the population is rising worldwide. Indeed, the increase in developing countries is likely to be even greater than in developed countries. Although rates vary from year to year and birth cohort to cohort, it is highly likely that unless suicide pre-vention becomes a great deal more effective than at present, more and more older people will kill themselves in the coming years.
As with younger people, completed suicide in old age may be

As with younger people, completed suicide in old age may be 
seen as part of a continuum from suicidal thinking through delib-erate self-harm (which does not lead to death), to completed suicide. An added component within this continuum for older people is that of ‘indirect self-destructive behaviour’ , such as refusal to eat and drink or ‘turning one’s face to the wall’ which is clearly intended to hasten death. Finally, although this section does not deal with euthanasia and related issues, assisted suicide in people with termi-nal illness such Alzheimer’s disease and cancer may also be seen as part of the suicide continuum.
Suicidal thinking in community-dwelling 
elderly people
A number of studies have explored this issue. Fleeting thoughts of 
suicide or the idea that life is not worth living occur in up to about 15 per cent of community-dwelling older people,
(2) but serious 
consideration of suicide is very much less.(3) It is those older people

consideration of suicide is very much less.(3) It is those older people 
with mental disorders, mostly depressive, who show a higher frequency of thoughts that life is not worth living and harbour ideas of committing suicide. It seems logical to suppose, therefore, that depressed elders should be the target of suicide prevention strategies.
Indirect self-destructive behaviour

Unlike the young, some elderly people have the possibility open to them of behaving passively in such a way as to hasten death. This may happen either by refusing medical treatment essential to main-tain life, or simply by declining to eat and drink—‘turning one’s face to the wall’ . As regards the latter, many people, especially non-medical, believe that this is reasonable behaviour akin to so-called ‘rational suicide’ , and court rulings have sanctioned it. There is no doubt that there are several cases in which a person’s right to refuse treatment or nutrition, for example during the terminal phase of cancer, should and would be respected. However, it has been argued that many of such cases suffer from undiagnosed but treatable depressive illnesses. Some support for this point of view was pro-vided by a questionnaire study of more than 1000 residential and nursing home administrators in the United States.
(4) Cognitive

(4) Cognitive 
impairment, loss events, refusing medication, food, and drink, lone-liness, feeling rejected by families are all risk factors for indirect sui-cidal behaviour in residential homes.
(5) It is wise, therefore, that no 
one should be permitted to turn his or her face to the wall before assessment for the presence of a treatable depressive disorder.Deliberate self-harm
Incidence
It is less possible to make a clear distinction between deliberate self-harm (DSH) and completed suicide in older than younger people. DSH at all ages has been quite extensively studied, but for obvious reasons mainly in hospital samples, and it is possible that several cases are undetected in the community. Broadly speaking the incidence curve for DSH is highest for the young and declines with age, whereas that for completed suicide rises with age. By the same token suicidal intent behind acts of DSH in older people is signiﬁ  cantly greater than in younger adults.
(6) In clinical practice

(6) In clinical practice 
it is therefore wise to consider deliberate self-harm in those over 75 as failed suicide.
Sex
As with completed suicide, rates for DSH differ quite widely from country to country. As with younger attempters, females outnum-ber males at a raw number ratio of approximately 3:2, but the proportionate  gender ratio is approximately unity because fewer 
males survive into old age. Contrast this with completed suicide where men clearly outnumber women.
Methods
Deliberate drug overdose is the favoured method for DSH at all ages in Western countries; in some others, corrosive poisons or detergents are used. The most common types of drug for overdose are benzodiazepines, analgesics, and antidepressants. After drugs, self-cutting is the next most frequent method.

Older people are more likely to be assigned a psychiatric diagnosis after DSH, about half suffering from major depressive disorder, up to about a third from alcohol abuse, and under 10 per cent from other disorders.
(7) Only about 10 per cent have no psychiatric 
diagnosis at all. Alcohol abuse together with depressive disorder augments the risk of DSH in older people. The status of cerebral organic disorder is uncertain because selection bias in reported case series reduces comparability. However, mild cognitive impair-ment and a co-morbid depressive disorder have been considered risk factors, and should be borne in mind by the clinician, if only on common-sense grounds. Personality factors have been impli-cated in DSH in older people, but research data are too poor and too few to make reliable statements on the subject.

Risk factors for deliberate self-harm in elderly people include: physical illness; widowhood and divorce or separation from a cohabitee; social isolation and loneliness (not the same thing); or simply living alone.
(6,7) Unresolved grief, usually after death of a 
spouse, is a commonly found risk factor. The threat of transfer to a nursing home is, unsurprisingly, a precipitant of deliberate self-harm, although once an elderly patient is transferred to institutional care the risk of an overdose or some other attempt at suicide is reduced, probably because of lower access to the means and higher supervision. Surprisingly perhaps, terminal illness is not commonly found in older patients who attempt suicide but 8.5.7 suicide and deliberate self-harm in elderly people

SECTION 8  the psychiatry of old age 1566
fail, although hitherto undiagnosed but treatable physical disorders 
are sometimes revealed.
In keeping with the fact that more older suicide attempters are 
assigned a psychiatric diagnosis than younger ones is the fact that about 50 to 90 per cent, depending on the case series, undergo some form of psychiatric treatment as a result of the act of deliber-ate self-harm. Although fewer older people commit DSH than younger ones (about 5 per cent compared with 12 per cent) the risk of subsequent completed suicide is higher, compared with people of all ages (about 7 per cent compared with 3 per cent). Individual risk factors for later successful suicide include being male, having a prior psychiatric history, divorce, and current treatment for a persistent depressive illness.
(6, 8)
Completed suicide
Rates

(6, 8)
Rates
The point has already been made in the opening paragraph of this chapter that suicide rates are still highest in the oldest old in most countries. Men outnumber women by about three or four to one in most countries; the exception being rural China.
(1) However, suicide 
rates in the old have in fact been declining in many industrialized countries over the past 25 years, whilst those in young males have been rising—a reminder of the maxim that rates in all groups can and do vary over time and between countries, so that general 
conclusions about suicide should always take context into account. 
The reasons for incidence variations are discussed elsewhere, but 
socio-economic conditions and access to means play their part 
with the old as well as younger suicide victims.
Suicide at all ages is associated with divorce, widowhood, and

Suicide at all ages is associated with divorce, widowhood, and 
single marital status. Widowers are more likely to kill themselves than widows, which has relevance for old age psychiatry, since in the overall population there are more old widowers than young ones.
Methods
Methods of suicide chosen by older people depend to a great extent on availability. In the United States, ﬁ  rearms are used by the major-
ity of older men who kill themselves.
(9) Shooting is also commonly 
chosen in Australia and Finland. In the United Kingdom, which has more stringent ﬁ  rearms control, drug overdose, especially in 
women and frequently with combination analgesics, hanging (especially in men), suffocation, or jumping from tall structures are preferred methods.
(10) In Japan hanging, in Hong Kong jump-

ing from one of the many very high buildings, and in Sri Lanka organophosphate poisoning are the commonest means in use.
Planning
Suicide in older persons is marked by careful planning and about half of the victims leave a note to indicate why or to conﬁ  rm that 
they have killed themselves.
(10) Suicide pacts are generally rare, 
but half of those that do occur involve people over 65. A previous history of a suicide attempt (DSH) is found in about a third of those older people who kill themselves.
Studies, including case-control, in the United States, Scandinavia, and the United Kingdom have found that 70 per cent of older suicide victims suffer from a mental illness, most commonly a major depressive disorder at the time they die.
(11–14)  Chronic symptoms

(11–14)  Chronic symptoms 
of depression and a ﬁ  rst depressive illness in later life are associated 
with a greater risk of suicide. Untreated or inadequately treated depressive illness is also found more commonly in elderly suicides. By contrast with younger suicide victims, alcohol and drug abuse rates are lower in elderly people, although co-morbid depression and alcohol abuse do occur more frequently than by chance. Schizophrenia or schizophrenia-like disorders are found less commonly in older than younger suicides. Similarly, cerebral organic impairment or dementia are infrequent and even absent from some series of cases. There has been more recent interest in the role of personality in suicide in older people. In various studies obsessional or anankastic traits which researchers have called ‘low openness to experience’ have been shown to predispose to suicide.
(14,15)
Co-morbid physical illness

(14,15)
Co-morbid physical illness is, on common-sense grounds alone, likely to be a risk factor for suicide in older people and this has been conﬁ  rmed in a number of studies.
(16–18)  Also, older people 
are much more likely to have visited their primary care doctor in the month prior to killing themselves than are younger suicide victims, and furthermore more likely to complain of physical than mental symptoms. Nevertheless, suicide to bring about the prema-ture ending of a terminal illness or the avoidance of pain, although found to be a factor in studies of a variety of speciﬁ  c diseases, is not 
as common as one might imagine.
Social risk factors
Social risk factors for suicide in old age have been found to include: isolation and poor social integration; lack of a person to conﬁ  de in; 
and concerns over dependence or a move from home to residential care.
(13,18–20)  Bereavement by itself is no more of a risk factor in

(13,18–20)  Bereavement by itself is no more of a risk factor in 
older than the younger suicides, but a grief reaction prolonged for more than a year has been found to increase the risk.
Risk assessment
The study of suicide at any age is primarily for the purpose of prevention. In older people this means that, episodes of deliberate self-harm need to be considered as serious, even and perhaps espe-cially when they do not appear to be so. A quantitatively small overdose of a relatively less lethal drug is frequently no indication of the seriousness of suicidal intent. Primary care doctors should be aware of the suicide risk in those attending with physical disor-ders, especially where the patient’s complaints seem to be out of proportion to the actual evidence of disease. Nor is the identiﬁ  ca-

tion of a physical illness a reason to relax vigilance over suicide risk. Dismissal of an older person’s wish to die as ‘rational’ is probably wrong in the great majority of cases, but in any case should never be done before a thorough assessment of the mental state concen-trating in particular on depressive disorder. Anxiety is frequently 
so prominently a presenting symptom of depressive disorder in 
elderly people, that other manifestations, such as suicidal thinking, may be overlooked. Whilst elderly people respond well to antide-pressant medication, many live alone. Thus, a prescription for perhaps a month of treatment might be an enhancement of suicide risk. It is therefore prudent either to arrange close supervision or administration of medication by a carer rather than the patient

1567
themselves, or for no more than a week’s supply to be dispensed at 
a time. Pharmacists may be willing to assist in this by providing proprietary boxes with compartments for each dose.
Harwood, D. (2008). Suicide in older persons. In The Oxford textbook of old 
age psychiatry  (eds. R. Jacoby, C. Oppenheimer, T. Dening, and 
A. Thomas) Chapter 29 iii. Oxford University Press, Oxford.
Hawton, K. and van Heeringen, K. (eds.) (2000). The international handbook 
of suicide and attempted suicide . Wiley and Sons, Chichester.
Pirkis, J. and Burgess, B. (1998). Suicide and recency of health care contacts: 
a systematic review. The British Journal of Psychiatry ,173, 462–74.
 1. http://www.who.int/mental_health/prevention/suicide/
country_reports/en/index.html
 2. Kirby, M., Bruce, I., Radic, A., et al. (1997). Hopelessness and suicidal 
feelings among the community dwelling elderly in Dublin. Irish Journal 
of Psychological Medicine ,14, 124–7.

2. Kirby, M., Bruce, I., Radic, A., et al. (1997). Hopelessness and suicidal 
 3. De Leo, D., Cerin, E., Spathonis, K., et al. (2005). Lifetime risk of 
suicide ideation and attempts in an Australian community: prevalence, suicidal process, and help-seeking behaviour. Journal of Affective 
Disorders ,86, 215–24.
 4. Osgood, N.J. and Brant, B.A. (1990). Suicidal behavior in long-term 
care facilities. Suicide & Life-threatening Behavior ,20, 113–22.
 5. Draper, B., Brodaty, H., Low, L.F., et al. (2002). Self-destructive 
behaviors in nursing home residents. Journal of the American Geriatrics 
Society ,50, 354–8.
 6. Hawton, K. and Harriss, L. (2006). Deliberate self-harm in people aged 
60 years and over: characteristics and outcome of a 20-year cohort. International Journal of Geriatric Psychiatry ,21, 572–81.

 7. Draper, B. (1996). Attempted suicide in old age. International Journal 
of Geriatric Psychiatry ,11, 577–87.
 8. Hepple, J. and Quinton, C. (1997). One hundred cases of attempted 
suicide in the elderly. The British Journal of Psychiatry ,171,
42–6.
 9. Kaplan, M.S., Adamek, M.E., Geling, O., et al. (1997). Firearm suicide 
among older women in the US. Social Science & Medicine ,44,
1427–30.
10. Harwood, D.M.J., Hawton, K., Hope, T., et al. (2000). Suicide in older 
people: mode of death, demographic factors, and medical contact before death. International Journal of Geriatric Psychiatry ,
15, 746–3.
11. Conwell, Y., Duberstein, P .R., Cox, C., et al. (1996). Relationships of 
age and axis I diagnoses in victims of completed suicide: a psychological autopsy study. The American Journal of Psychiatry ,153,
1001–8.

1001–8.
12. Waern, M., Runeson, B.S., Allebeck, P ., et al. (2002). Mental disorder 
in elderly suicides: a case-control study. The American Journal of 
Psychiatry ,159, 450–5.
13. Beautrais, A.L. (2002). A case-control study of suicide and attempted 
suicide in older people. Suicide & Life-threatening Behavior ,32, 1–9.
14. Harwood, D.M.J., Hawton, K., Hope, T., et al. (2001). Psychiatric 
disorder and personality factors associated with suicide in older people: a descriptive and case-control study. International Journal of Geriatric 
16, 155–65.
15. Duberstein, P .R., Conwell, Y., and Caine, E.D. (1994). Age differences 
in the personality characteristics of suicide completers: preliminary ﬁ ndings from a psychological autopsy study. Psychiatry ,57, 213–24.
16. Conwell, Y., Lyness, J.M., Duberstein, P ., et al. (2000). Completed

16. Conwell, Y., Lyness, J.M., Duberstein, P ., et al. (2000). Completed 
suicide among older patients in primary care practices: a controlled study. Journal of the American Geriatrics Society ,48, 23–9.17. Waern, M., Rubenowitz, E., Runeson, B., et al. (2002). Burden of illness 
and suicide in elderly people: a case-control study. British Medical 
Journal ,324, 1355–7.
18. Harwood, D.M.J., Hawton, K., Hope, T., et al. (2006). Life problems 
and physical illness as risk factors for suicide in older people: a descriptive and case-control study. Psychological Medicine ,36,
1265–74.
19. Turvey, C.L., Conwell, Y., Jones, M.P ., et al. (2002). Risk factors for 
late-life suicide: a prospective, community-based study. The American 
Journal of Geriatric Psychiatry ,10, 398–406.
20. Duberstein, P .R., Conwell, Y., Conner, K.R., et al. (2004). Poor 
social integration and suicide: fact or artefact? A case-control study. 
Psychological Medicine ,34, 1331–7.
8.5.8 Sex in old age

A Darwinian sees man as devoted to reproducing himself. The 
decline of fertility with age makes one question the biological purpose of sexuality in the senium. Is it simply the remains of a once useful behaviour, a vestigial characteristic? The fact remains that sexual interest and sexual activity, both as sources of enjoy-ment and as important components of pair bonding, continue among men and women even into extreme old age. However, as Alex Comfort memorably remarked, ‘old people give up sex for the same reasons that they give up cycling—general inﬁ  rmity, fear of 
looking ridiculous, no bicycle’ .
(1) Or, more soberly: the common 
obstacles to the continued enjoyment of sex in old age are illness, attitudes, and demography.
Surveys of sexuality in old age

A comprehensive discussion of surveys in this ﬁ  eld can be found in 
Bouman.(2) These vary widely in their focus, setting, methods, and 
target age groups. The details are of great interest but only the main themes and a few illustrative examples can be described here.
Methodology
As with all surveys, one has to consider what factors inﬂ  uenced 
the selection (and self-selection) of the responders. In general, participants in these studies tend to be better educated and more liberal in their attitudes than their contemporaries; and important groups, such as people with chronic illness, may be under (or over) represented, depending on the setting of the survey.
Cross-sectional and longitudinal studies

Attempts to assess the effects of ageing on sexuality by surveying different age-groups at a single point in time are vulnerable to cohort effects— the sexual experience of those brought up before 
the Second World War is different from that of people whose child-hood was in the 1950s, and need have nothing to do with age. 
Longitudinal studies are demanding and costly, but they reveal the effects of ageing more clearly, and they also allow individual patterns, stable over time, to be identiﬁ  ed. For example, the series 8.5.8 sex in old age

SECTION 8  the psychiatry of old age 1568
of studies conducted at Duke University showed that although the 
prevalence  of sexual interest and activity in both men and women 
decreases with age, individual  patterns of sexuality tend to be stable 
until some event (such as illness or loss of a partner) disrupts the pattern.
(3)
Sexual interest and sexual pleasure
There is more to sex than actual intercourse, especially in old age. A consistent ﬁ  nding is that in both sexes interest in sex is more 
resistant to ageing than is sexual activity, even when non-coital activity is included. For example, in a cross-sectional study of volunteer respondents aged 80 or over, living in a residential home in the United States,
(4) 88 per cent of the men and 71 per cent of

(4) 88 per cent of the men and 71 per cent of 
the women enjoyed daydreams and fantasies about sex, 82 per cent of the men and 61 per cent of the women engaged in touching and caressing, while 63 per cent of the men and 30 per cent of the women had sexual intercourse ‘at least sometimes’ . Janus and Janus
(5) surveyed 2765 subjects in the United States by question-
naire, supplemented by 125 interviews. They found less reduction of activity in the older groups than had been found in earlier surveys, probably because they did not conﬁ  ne the question to 
coitus. In every age group men thought that they were more active than 3 years previously, but women, particularly those over 50, noted a decline. Unlike earlier studies foreplay was discussed, and the authors concluded that older men gain greater pleasure and experience more intimacy and warmth after coitus than younger men.
Obstacles to continued sexual activity

The commonest reasons given by people for a decline in their accustomed level of sexual activity were illness, and the loss of their partner.
(3) Interestingly, women (but not men) also gave illness of 
their partner as a reason. This may reﬂ  ect the traditional male role 
in initiating sexual activity, and also perhaps the fact that husbands tend to be older (therefore more at risk of illness) than their wives. For example, in a Swedish community study of 85-year olds,
(6)
participation in sexual intercourse was reported by 10 per cent of married women but only 1 per cent of the unmarried women, and by 22 per cent of married men compared to 13 per cent of the unmarried men. The rates for sexual interest (as opposed to activity) were higher: 46 and 37 per cent for married and unmarried men respectively; 24 and 15 per cent for married and unmarried women.
Attitudes to sexuality

Attitudes towards sexuality in old age—as revealed in responses to systematically varied vignettes—have become generally more positive over the last half-century, among both younger and older people.
(2,7) Probably this is true also of professional attitudes, and 
where this matters most is among the staff caring for older people in institutional settings. The evidence suggests that care staff who are older, better educated and have had vocational training, and who have more experience of caring, are likely to be more open to the sexual needs of their residents. However as Bouman
(2) points 
out, the same cannot be said of health policies and strategy. Government guidance on the care of older people has ignored their sexuality, and in most ofﬁ  cial surveys and policies on sexual issues, 
people aged 60 or more are excluded from consideration.Demography

With increasing life-expectancy many marriages continue well into the 9th decade of one or both partners. Divorce has now overtaken death as the main cause for the ending of a marriage, though this does not necessarily mean increasing numbers of people left single in old age. Many older people experience second or third marriages (or cohabitations), and the age gap between the partners in these new relationships tends to be larger than that between partners still in their ﬁ  rst marriage. The complex effects on family structure of 
these different social trends are analysed by Harper.
(8) She shows

(8) She shows 
that married older people have higher levels of health, social par-ticipation, and life satisfaction than those not married, and they live longer; while divorced men (compared to women, and to wid-owers) are the most disadvantaged in those respects. T o this we can add (based on the survey data mentioned above) that in old age married people also enjoy greater opportunities than the unmarried for sexual expression.
Sexual orientation
Much less is known and written about the sexual lives of older peo-ple who are not heterosexual in their orientation. Despite the pre-vailing trend in Western societies towards valuing diversity, most older homosexual people in their earlier lives will have feared—or faced—stigma, discrimination, even the threat of criminal proce-dure, and may still face such discrimination. Further discussion of this important group of people can be found in Bouman.
(2)
Sexuality and dementia

(2)
The effect of dementia on sexual interest and activity is unpredict-able. Most often it is associated with a decline in interest, but sometimes (probably in less than 10 per cent of cases) a person with dementia may become more sexually demanding, or may lose the ability to judge when the expression of sexual interest is unwanted or out of place.
(2, 9) The effect of the patient’s dementia 
on the spouse is also difﬁ  cult to predict. In some couples the 
physical relationship continues as an important expression of their affection, support, and concern for each other. More commonly, sexual activity declines. For example, Wright
(10) followed a group 
of couples in which one partner had dementia, alongside a control group of couples without dementia. Only 27 per cent of the afﬂ  icted 
couples continued sexual contact over the 5 years after diagnosis, compared to 82 per cent of the control couples.

Patients with dementia who have altered sexual behaviour, or 
who can no longer make reliable judgments about potentially sex-ual social situations, become vulnerable to misunderstanding, exploitation, or censure. In marriages the impact of these changes is often borne alone by the spouse, who also keeps them hidden from others. But people with dementia who live alone or who go into institutional care (even if only temporarily, into hospital perhaps) are not so protected, and clinical staff may be asked to intervene—to control behaviour that has offended or is harmful to 
others, or to reduce risk to a vulnerable patient. It may be crucial 
to establish whether such a patient is making an autonomous choice (for example, to engage in sexual contact with a fellow resi-dent) or whether their failure of understanding is being exploited; and Lichtenberg and Strzepek

(11) describe a helpfully structured 
approach to this question.

1569
Normal sexual function in old age
The normal human sexual response cycle and the physiology of 
sexual intercourse are described in Chapter 4.11.1 in this textbook. These descriptions hold true for sexually active older people, although age does bring some relatively minor physical changes (see Table 8.5.8.1, based on data from Masters and Johnson
(12))—
changes experienced by some but not necessarily by all. The most noticeable of these are probably the much longer refractory period in older men (the interval which follows ejaculation before renewed erection is possible), and the oestrogen-dependent changes in vaginal tissue and lubrication in older women. However, according to the self-reports of older sexually active people, the capacity for sexual pleasure and the quality of orgasms are not at all affected by age.
Sexual dysfunction in old age

The range of sexual dysfunctions is discussed in detail in Chapter 4.11.2 in this textbook. In old age, as mentioned earlier, physical illnesses and their treatm ents assume incr easing impor tance 
in curtailing the normal sexual activity and interest of an estab-lished couple. Likewise, with ageing, the balance between psycho-logical and physical factors in the causation of a sexual problem, tips towards the physical. An example of this is erectile dysfunction, where a notable increase in research into the physiology of penile erection has led to a number of effective physical treatments, especially relevant to erectile problems associated with illnesses common in old age (such as diabetes and vascular disorders).
(13,14)

(13,14)
However, a clearer understanding of the physical components of a problem does not diminish the importance of psychological factors. Myocardial infarction, probably accompanied by hyperten-sion and atherosclerosis, provides a good example. After the infarc-tion the couple may misperceive the breathlessness of orgasm as cardiac distress, and they may need encouragement to resume sexual relations which may reduce the risk of further infarction.
(15)
Even a hospital admission interrupts the couple’s sexual routine which may then be difﬁ  cult to resume.
Some of the most common physical causes of sexual dysfunction 
are listed in Tables 8.5.8.2, 8.5.8.3, and 8.5.8.4.Treatment of sexual problems in old age

The treatment of sexual dysfunction is founded on a comprehen-sive understanding of the problem. It begins with listening. Perhaps this is a statement of the obvious—except that the emotional power of sexuality makes it hard for patients and their partners to speak about sex, and for others to listen properly. Sexual histories are rarely taken as a routine part of the assessment of older people,
(2)
and even when patients disclose a sexual problem, their doctor may shrink from embarking on an exploration of the difﬁ  culty. Y et there

(2)
and even when patients disclose a sexual problem, their doctor may shrink from embarking on an exploration of the difﬁ  culty. Y et there 
is good evidence that opening up communication about a sexual problem—not only between clinician and patient but also (helped by the clinician) between sexual partners—forms a large part of successful treatment, and sometimes may be all that is needed. Even patients attending a specialized clinic may be satisﬁ  ed by receiving 
assessment and information, without necessarily wanting active treatment.
(13)
Sexual problems come to the notice of many different medical

(13)
Sexual problems come to the notice of many different medical 
and surgical specialties (gynaecology, urology, genitourinary medicine, diabetology, endocrinology) who have expertise in the physical treatments now available, and sometimes also in the psy-chological and relationship components of the dysfunctions that they treat. In other cases the psychiatrist may be helping the couple to work with a physical treatment that one of them is receiving, and to make the most of the improvements in sexual function that it offers.
Behavioural treatment for sexual dysfunction, ﬁ  rst described 
by Hunter,
(16) was developed by Masters and Johnson.(17)
Their Sensate focus exercise  (see Chapter 4.11.2) is a simple behav-
ioural technique that can be very effective in helping couples in whom sexual intercourse has become (for whatever reason) difﬁ  -

cult, painful, or disappointing, and who have then retreated from all pleasurable physical contact with each other. In this technique attention is removed from intercourse (in fact intercourse is for-bidden), and instead the focus is put on renewing the partners’ pleasure in mutual touch and caressing for its own sake.Table 8.5.8.1  Physical changes of ageing
Male Female
Retained Nil Nipple erection
Clitoral tumescence and retraction
Reduced Penile and nipple erection Vaginal lubrication and
Testicle elevation expansionPower of ejaculation Uterine elevationRectal contractions Bartholin gland secretion
Orgasmic contractions
Lost Flush Breast engorgement
Scrotal swelling FlushRe-erection Swelling of labia majora
Ejaculatory inevitability
Prostate contractions
Other Refractory period >24 h8.5.8 sex in old age

Table 8.5.8.2  Medical factors affecting sexual function
Drugs reducing sexual drive Drugs reducing 
testosteroneDrugs blocking 
physical arousal
Dopamine antagonists Digoxin Thiazide diuretics
Major tranquillizers Cimetrdine Some β-blockers
Metaclopamide Cyproterone
5-HT2 agonists–SSRIs except 
nefazodone, trazodone, ﬂ  uvoxamineFinasteride
Benzodiazepines Oestrogens
Progesterone
Table 8.5.8.3  Surgical procedures affecting sexual function
Transurethral prostatectomy leads to retrograde ejaculation
Pararectal surgery damages nervi erigentesIndwelling catheters and pessariesMutilation affecting body imageSurgery to genitalia

SECTION 8  the psychiatry of old age 1570
There is little scope for pharmacological treatment of most sexual 
difﬁ culties arising in old age, other than erectile dysfunction.(13,14)
Hormonal treatments are no longer thought to be helpful except 
where deﬁ  ciencies have been clearly demonstrated. The com monest 
hormonal treatment in old age is probably the use of oestrogen (topically) in dyspareunia. Treatment of hypersexuality and sexual aggression in the context of dementia is difﬁ  cult: pharmacological 
methods have been reviewed by Series and Degano.
(18)
Ageing brings increasing diversity. This certainly applies to sexual behaviour. Those who work in the ﬁ  eld of old age psychiatry can

(18)
Ageing brings increasing diversity. This certainly applies to sexual behaviour. Those who work in the ﬁ  eld of old age psychiatry can 
help their patients by understanding this diversity, making it safe and acceptable for patients to talk about whatever sexual concerns they have, and helping them in the acquisition of all the information they need. Sex in old age is not the frightening imperative of the teenager, but it can still contribute greatly to the quality of life.
Bouman, W.P . (2008). Sexuality in later life. In The Oxford textbook of old 
A. Thomas) (chapter 37). Oxford University Press, Oxford.
Gott, M. (2005). Sexuality, sexual health and ageing . Open University Press, 
Maidenhead, Berkshire.
Greengross, W. and Greengross, S. (1989). Living, loving and ageing. Sexual 
and personal relationships in later life . Age Concern England, Mitcham, 
Surrey.

Surrey.
Leiblum, S.R. and Rosen, R.C. (eds.) (2000). Principles and practice of sex 
therapy . The Guildford Press, New Y ork.Warner, J. (2000). Sexuality in dementia. In Dementia  (2nd edn) 
(eds. J. O’Brien, D. Ames, and A. Burns), pp. 267–71. Arnold, London.
 1. Comfort, A. (1980). Practice of geriatric psychiatry . Elsevier, New Y ork.
 2. Bouman, W.P . (2008). Sexuality in later life. In The Oxford textbook of 
old age psychiatry  (eds. R. Jacoby, C. Oppenheimer, T. Dening, and 
 3. George, L.K. and Weiler, S.J. (1981). Sexuality in middle and later life; 
the effects of age, cohort and gender. Archives of General Psychiatry ,
38, 919–23.
 4. Bretschneider, J.G. and McCoy, N.L. (1988). Sexual interest and

 4. Bretschneider, J.G. and McCoy, N.L. (1988). Sexual interest and 
behavior in healthy 80- to 102-year olds. Archives of Sexual Behavior ,
17, 109–29.
 5. Janus, S.S. and Janus, C.L. (1993). The Janus report on sexual behavior .
 6. Skoog, J. (1996). Sex and Swedish 85-year olds. The New England 
Journal of Medicine ,334, 1140–1.
 7. Gott, M. and Hinchliff, S. (2003). How important is sex in later life? 
The views of older people. Social Science & Medicine ,56, 1617–28.
 8. Harper, S. (2008). Sociological approaches to age and ageing. In 
The Oxford textbook of old age psychiatry  (eds. R. Jacoby, 
C. Oppenheimer, T. Dening, and A. Thomas) (chapter 2). Oxford University Press, Oxford.
 9. Haddad, P .M. and Benbow, S.M. (1993). Sexual problems associated 
with dementia: part 1. Problems and their consequences. International 
Journal of Geriatric Psychiatry ,8, 547–51.

9. Haddad, P .M. and Benbow, S.M. (1993). Sexual problems associated 
10. Wright, L.K. (1998). Affection and sexuality in the presence of 
Alzheimer’s disease: a longitudinal study. Sexuality and Disability ,
16, 167–79.
11. Lichtenberg, P .A. and Strzepek, D.M. (1990). Assessment of 
institutionalized dementia patients’ competencies to participate in 
intimate relationships. The Gerontologist ,30, 117–20.
12. Masters, W. and Johnson, V . (1966). Human sexual response . Churchill, 
London.
13. Melman, A. and Christ, G.J. (2002). The hemodynamics of erection and 
the pharmacotherapies of erectile dysfunction. Heart Disease ,
4, 252–64.
14. Trost, L., Kendirci, M., and Hellstrom, W.J.G. (2006). Erectile 
dysfunction in the aging man: current options for treatment. Aging Health ,2, 71–86.
15. Kellett, J. (1987). Treatment of sexual disorder: a prophylaxis for major

15. Kellett, J. (1987). Treatment of sexual disorder: a prophylaxis for major 
pathology? Journal of the Royal College of Physicians ,21, 58–60.
16. Hunter, J. (1782). Venereal disease . London.
17. Masters, W.H. and Johnson, V .E. (1970). Human sexual inadequacy .
18. Series, H. and Degano, P . (2005). Hypersexuality in dementia. 
Advances in Psychiatric Treatment ,11, 424–31.Table 8.5.8.4  Diseases affecting sexual function
Diabetes
Myxoedema, pituitary tumoursNeuroﬁ  bromatosis, paralysis, myotonia dystrophica, autonomic neuropathyPeyronie’s diseaseMalignancy and infections of genitalia and prostate, vaginal ﬁ  stulasLiver failure leading to higher oestrogensArthritisHypertension, vascular diseases, myocardial infarction
Respiratory distress
Depression, schizophrenia, cortical dementias

8.6
Special features of psychiatric 
treatment for the elderly
Three themes underlie the topics in this chapter.
Old age is a time of multiple problems
Physical, psychological, and social problems often occur together, 
linked by chance or causality in the life of the old person. Very rarely can one problem be dealt with in isolation, and many different sources of expertise may be engaged with a single individual. Therefore good coordination between different agents is essential in old age psychiatry, both for the individual patient and in the overall planning of services.
Clear boundaries between ‘normality’ and ‘disease’ are 
rare in old age
Many of the pathologies characteristic of old age are gradual in

Many of the pathologies characteristic of old age are gradual in 
onset and degenerative in nature, and more due to failures in pro-cesses of repair than to an ‘external foe’ , so the distinction between disease and health is often quantitative rather than qualitative. ‘Normality’ becomes a social construct with ﬂ  uid borderlines, 
containing the overlapping (but not identical) concepts of ‘statistically common’ and ‘functionally intact’ . Thus the popular perception of normal old age includes the ‘statistically common’ facts of dependence and failing function, whereas ‘intactness’ (excellent health and vigorous social participation) is seen as remarkable rather than the norm. But the boundaries of ‘old age’ are also socially constructed—in developed countries good health at the age of 65 would nowadays be regarded as a normal middle-aged experience, whereas superb health at 95 would still be some-

thing noteworthy.
Since some degree of physical dependence, forgetfulness, and 
vulnerability to social exclusion is expected in old age, meeting those needs is also regarded as a ‘normal’ demand on families and community agencies such as social services, rather than the respon-sibility of health care providers. As the severity of the needs increases, however, so also does the perceived role of health professionals, both as direct service providers and in support of other agencies.
Lack of competence is common in old age
Because of the high prevalence of cognitive impairment in old age (especially among the ‘older old’), questions frequently arise as to the competence of patients to make decisions. Older people who cannot manage decisions alone may come to depend increasingly 
on others for help; or, resisting dependence, they become vulnerable

on others for help; or, resisting dependence, they become vulnerable 
through neglect of themselves or through the injudicious decisions they make. When an incompetent person is cared for by a spouse or family member, the danger of self-neglect or of ill-considered decisions is lessened, but instead, there are the risks of faulty deci-sions by the caregiver (whether through ignorance or malice), and also risks to the health of the caregiver from the burden of depen-dence by the incompetent person. Legal mechanisms, differing from one country to another, exist to safeguard the interests of incompetent people.
These three themes will be developed further, and with them the 
following special topics:
1 multiple problems: including sleep disorders in old age, medica-
tion in old age psychiatry, and psychological treatments in old age psychiatry;
2 blurred boundaries of normality: including the role of specialist 
services and support between agencies;

3 incapacity and dependence: including balancing the needs of 
patients and caregivers, abuse of older people, ethical issues, and medico-legal arrangements for safeguarding decisions.
Multiple problems
Sleep disorders in old age
Useful reviews of this topic may be found in Anconi-Israel and Ayalon,
(1) Sivertsen and Nordhus,(2) and Mosimann and Boeve.(3)
More detailed general discussion of sleep and its disorders will be found in Chapters 4.14.1–4.14.4 of this textbook.
(a) Normal changes with age
With age, the architecture of sleep changes—in fact, most of the change occurs before the age of 60. Sleep is divided into shorter periods interspersed with wakefulness or brief arousals, there is a decrease in total sleep time and in sleep efﬁ  ciency (the ratio of

time asleep to time in bed), and there is less stage 4 (deep) and more stage 1 and 2 (shallow) sleep, without an increase in the proportion of rapid-eye-movement (REM) sleep. This change in sleep architecture is conventionally associated with changes in circadian rhythms with age, such as decreased amplitude and phase length of these rhythms (but see Monk
(4) for a critical review).

SECTION 8  the psychiatry of old age 1572
Many people adapt to these changes, but others ﬁ  nd the altered 
pattern distressing. Thus the borderline between normal and prob-lematic sleep is blurred, because subjective assessments of sleep quality are not necessarily matched by objective measures (such as polysomno graphy); consequently the definition of ‘insomnia’ hinges not only on features of night-time sleep, but on impaired functioning in the daytime.
The majority of healthy older people have no complaints about their sleep, but there is a strong association between poor sleep and other health problems, and sleep problems make a material contri-bution to the impaired quality of life suffered by people with comorbid illness. In a study of patients in primary care,
(5) a positive

(5) a positive 
answer to even one question about sleep (‘do you feel excessively sleepy during the day?’) predicted the quality of life related to phys-ical or mental health problems. Attention to improving sleep in these patients can improve their well-being, but too often the sleep problem is missed in the general assessment of the patient. Impaired sleep can have serious consequences: it is associated with symp-toms of anxiety and depression, an increased risk of falls, and diminished memory and cognitive functioning.
(1)
(c) Causes of disordered sleep
These include the following:
1Environmental causes : e.g. a strange bed, noise, cold or heat, or 
loss of a familiar bed companion (e.g. through bereavement).
2Physical causes : sleep can be broken by pain, stiffness (e.g.

2Physical causes : sleep can be broken by pain, stiffness (e.g. 
Parkinson’s disease or arthritis), limb movement (restless legs syndrome, periodic movements of sleep), breathlessness (cardiac failure or sleep apnoea), the need to urinate (prostatic disease or urinary tract infection), eating too close to bedtime, or dehydra-tion (e.g. voluntary restriction of ﬂ  uids to prevent nocturia).
3Medication : alcohol, especially if taken to relieve anxiety or to 
assist sleep (since the rapid metabolism of alcohol leads to rebound anxiety and wakefulness), and antidepressants such as selective serotonin reuptake inhibitors ( SSRIs ) can cause wake-
fulness or nightmares. Information on the numerous other med-ications which may impair sleep can be found in Anconi-Israel and Ayalon.
(1)
4Psychological causes : for example, anxiety, depression, hypoma-

(1)
nia, and paranoid illness. Often a sleep problem is triggered initi-ally by a physical cause, but is then maintained by the patient’s anxiety about wakefulness.
5Sleep in dementia : changes in sleep rhythm in dementia are 
similar to those of normal old age, but often more severe: day-time drowsiness or napping, difﬁ  culty in falling asleep  at night,

similar to those of normal old age, but often more severe: day-time drowsiness or napping, difﬁ  culty in falling asleep  at night, 
decreases in slow wave sleep and in rapid-eye-movement sleep. However, another common cause of sleep impairment is the use of benzodiazepines or major tranquillizers to treat behaviour disturbances: the patient may end up drugged in the day and wakeful at night. A partial remedy may be to create an overriding diurnal rhythm (e.g. by attendance at day care or a programme of physical activity in the day), together with the minimal use of medication at night. Patients in institutional care are particu-larly likely to be deprived of the normal cues for circadian rhythms: quiet and darkness at night, bright daylight in the morning, and physical activity in the day. On the other hand sleep time may be strikingly increased in dementia, especially

in vascular dementia where it may be part of the apathy that is 
common in that dis ease.
(d) The parasomnias
The parasomnias that are common in old age are obstructive sleep 
apnoea (or sleep-disordered breathing); restless legs syndrome and periodic limb movements in sleep; and REM sleep behaviour disorder (RBD). They may range in severity from troublesome to severely disabling, and accurate recognition is important for all of them, because of the consequences both to the patients and to their bed partners if their diagnosis and treatment are missed. Further details can be found in the sources mentioned above,
(1,3)
but RBD warrants some further discussion here. This disorder is deﬁ ned as an ‘intermittent loss of the muscle atonia normally pres-
ent during REM sleep, and episodes of elaborate motor activity associated with dream mentation’ .
(6) Typically, in the early hours

(6) Typically, in the early hours 
the patient (usually male) shouts, thrashes around, and may attack his bed partner, without waking, and without any recollection of the episode when he does wake later. The importance of this condition lies in the fact that it is very distressing, and possibly dangerous, for the bed partner; it can often be treated effectively (with clonazepam); and it is strongly associated with the develop-ment (sometimes after a very long latent period, of a decade or more) of neurodegenerative disease—especially Lewy body dementia, Parkinson’s disease, or multisystem atrophy—the alpha-synucleopathies.
(6, 7)
(e) Management of sleep disorders
(i) Psychological methods
These are now the methods of choice with insomnia in older adults.
(2,8) Trials comparing psychological with pharmacological

(6, 7)
(2,8) Trials comparing psychological with pharmacological 
treatment, and with a combination of the two, show equivalent effects in the short-term, but a longer-term advantage to the psycho-logical methods. More importantly, it has also been shown that in secondary insomnia (‘insomnia occurring when a psychiatric con-dition, a medical condition, a non-insomnia sleep disorder, or a medication appears to precipitate and then appears to maintain insomnia’) it is not necessary to wait until the primary condition has been resolved: the insomnia can usually be effectively treated in its own right, and even if it is not completely cured, valuable improvements can be achieved.
(8) Likewise, psychological methods 
can be used to help in withdrawing medication in hypnotic dependent insomnia.
(9)
The methods used have generally been ‘multicomponent

(9)
The methods used have generally been ‘multicomponent 
behavioural treatments’ . The components include:
◆ Relaxation training
◆ Stimulus control (requiring the patient to leave the bedroom if they are not sleeping)
◆ Sleep restriction and sleep compression (using a ﬁ  xed time for 
getting up, progressively shortening the time in bed until it matches the time asleep)
◆ Cognitive restructuring (modifying the pre-sleep thinking patterns, which in insomnia usually include negative thoughts about the effects of sleep loss, and the use of worry and self-blame as an attempted strategy for controlling thoughts
(10))
◆ Sleep hygiene education (advice on the effects of tea, coffee, exercise, etc on sleep)

1573
Such treatment packages need not be dependent on sources of 
specialist expertise: Sivertsen and Nordhus(2) discuss the feasibility 
of treating insomnia psychologically within primary care.
(ii) Treatment of sleep problems in dementia
When cognitive impairment makes psychological treatment difﬁ  -
cult, pharmacological treatment may be necessary. Benzodiazepines (probably temazepam for preference) must be used very cautiously; they are dangerous in ambulant patients, though less so for a patient who is no longer mobile. Sedating antidepressants (e.g. tra-zodone) can be used instead. An atypical antipsychotic may be appropriate if there is severe anxiety and suspiciousness (some-times of delusional intensity) of the carer at night.
The sleep problems of the carer of a patient with dementia also 
need to be taken very seriously. The carer may beneﬁ  t from the

need to be taken very seriously. The carer may beneﬁ  t from the 
psychological measures outlined above, and can institute some of the measures (such as sleep hygiene) on behalf of the patient. Insomnia in a caregiver, caused by the wakefulness of the person 
cared for, can lead to rapid breakdown of the support system. If the 
patient’s sleep problem cannot be resolved then it is essential to give the carer the opportunity for uninterrupted sleep at times, through arranging residential respite care, a night-sitter, or some other form of relief.
The use of medication in old age psychiatry
Speciﬁ  c uses of medication for the various psychiatric disorders 
occurring in old age are dealt with in the relevant chapters. Here, three general principles will be discussed:
◆ medication as an experimental trial
◆ stopping medication
◆ compliance and concordance.
(a) Medication as an experimental trial

Starting medication for any condition ought to be treated as the test of a hypothesis. There should be a plan, shared with the patient, setting out the following:
1 how long the trial will last before a decision is made that the 
treatment is unsuccessful and should be ended;
2 which target symptoms will be monitored, and what records 
should be kept (by the patient or caregiver);
3 when progress will be reviewed;4 what side-effects might be developing and which of these should 
alert the patient to stopping the drug and contacting the doctor;
5 what will follow if the trial succeeds;6 what will be tried instead if the trial fails.
This watchful approach to medication is particularly important 
for people with dementia. Often the patient’s confusion, lack of insight, and communication difﬁ  culties mean that a tentative

for people with dementia. Often the patient’s confusion, lack of insight, and communication difﬁ  culties mean that a tentative 
diagnosis has to be based on scanty information. For example, disturbed behaviour in a patient in a nursing home may be due to depression, but the patient cannot describe the depressive symptoms. Clues to the diagnosis may come from the care staff (e.g. ‘She never jokes with us now’), and an empirical trial of an antidepressant may result in a resolution of the symptoms. However, the trial must be set up carefully and medication not thoughtlessly continued for months without review, merely because no one has asked whether 
it is helpful or not.
(b) Stopping medication

The decision to withdraw medication can be as valuable and infor-mative as the decision to start it, and documentation of the reasons for the decision is equally important (though often neglected). In delirium, medication may be contributing to the problem, particularly where a cocktail of medications has been built up over time—improvement after withdrawal of a drug gives valuable guidance for a future episode. Also, patients reaching the terminal stages of dementia should have their medication gradually decreased, to test whether it is still needed: drugs prescribed at an earlier stage to control behavioural syndromes are rarely, if ever, required for the entire course of the disease.
However, there are also reasons for being cautious about stop-
ping medication. Some drugs have important withdrawal effects (e.g. paroxetine and benzodiazepines). Medication that has been used prophylactically may seem to be unnecessary while the

ping medication. Some drugs have important withdrawal effects (e.g. paroxetine and benzodiazepines). Medication that has been used prophylactically may seem to be unnecessary while the 
patient is well, but when the drug is withdrawn the need for it is 
revealed. For example, a patient can remain well for years on an antidepressant following a severe depressive episode, or on a low dose of antipsychotic after a schizophrenic illness—until well-intentioned withdrawal of the drug, however carefully monitored, precipitates the return of the illness.
(c) Compliance and concordance

The word ‘compliance’ appears to imply that patients must be obe-dient in following instructions; but nowadays patients are seen more as partners in their own treatment, for which the word ‘con-cordance’ (when the partnership is successful) is more apt. The same principle of partnership in treatment decisions applies to older people, wherever possible. However, in addition to willing-ness to participate there needs to be the ability to do so, which in older people is often impaired by physical causes (such as arthritic hands which cannot open child-proof packaging, or poor vision which misreads instructions), and by psychological causes, espe-cially memory loss and temporal disorientation. Therefore patients will often need help in maintaining their concordance with treat-ment, through suitable packaging and memory aids (such as calen-dar boxes), or through supervision or administration of the tablets

by others. Families may take a long time to notice that their parent 
or grandparent, who has taken medication reliably for years, has started to miss or duplicate doses.
It is important to understand the feelings of a caregiver who 
takes responsibility for the medication prescribed for a patient with dementia, especially where it is being used to control behaviour. Anything prescribed on an ‘as-needed’ basis should be very carefully 
explained. The caregiver may be afraid of provoking the difﬁ  cult 
behaviour by offering the medication, or conversely of overdosing her relative into stupor, or she may feel guilty about meeting her own needs by giving drugs to another. Such feelings make it hard 
for a caregiver to judge objectively when discretionary medication should be used.
Psychological treatments in old age

Many older people prefer a ‘talking treatment’ to medication, and there is increasing evidence of the success of psychological inter-ventions with cognitively intact older people.
(11) Brief focused 
interventions are particularly suitable.8.6 special features of psychiatric treatment for the elderly

SECTION 8  the psychiatry of old age 1574
However, even mild cognitive impairment, too slight to amount 
to dementia but enough to interfere with grasp and retention, may hamper psychological treatment. For example, such a patient being treated psychologically for anxiety may try hard to cooperate with her therapist, only to be made more anxious as she fails to remem-ber the instructions, or to put them into practice, and so the sense of failure she feels elsewhere in her life is reinforced.
The principles of supportive psychotherapy and problem-

solving are always relevant, both on their own or in conjunction with medication: providing ‘unconditional positive regard’ for the patient; accepting a degree of dependence by the patient, while limiting its consequences; setting appropriate expectations so that the patient is not unnecessarily exposed to a sense of failure; open-ly facing realities that cannot be altered (such as loss, disability, and death); helping to think through practical problems as they arise.
Family and systems therapy
(12) has a particular role in old age 
psychiatry, because it explicitly recognizes the patient in his or her social context. Although family therapy requires special training, the principles of a family approach can be adopted by all those working with older people.
When patients are cognitively impaired, psychological approaches

When patients are cognitively impaired, psychological approaches 
generally focus more on the interaction between the patient and the caregivers, who can be helped to understand the patient and the reasons for her behaviour, as well as their own actions and the reciprocal effects that these have on her. For example, reminiscence therapy helps professionals to respond to patients as ‘whole people’ with individual lives, as well as helping patients to reconnect with their former identities, and to recover some of the conﬁ  dence they 
took for granted in the past.
Therapies based on music, dance, drama, art, and sensory stim-
ulation are also important in old age.
(13) They can help patients, 
individually or in groups, to express feelings and thoughts, bypassing the impairments of verbal skills which come with dementia.
The blurred boundaries of ‘normality’
We consider two examples of the way in which ‘normality’ is not clearly deﬁ  ned in old age.

First, social expectations allow for increasing dependency in the 
old, and many people have personalities better suited for protective relationships than for solitude and independence. People who have struggled with anxiety and loneliness in middle age can experience the onset of physical dependence as a kind of relief: now they can allow themselves to be looked after. What was a dysfunctional personality structure in earlier life becomes adaptive in old age. In contrast, the person who has always jealously guarded his or her personal boundaries will ﬁ  nd the adjustment to disability very 
hard. Determined refusal to accept necessary help converts a ‘nor mal’ 
preference for independence into a problem for others.
The second example concerns the idea of death. For a younger 
person to say that they were waiting for death would prompt a

person to say that they were waiting for death would prompt a 
psychiatrist to look for evidence of a depressive illness. In old age this way of thinking may be found in someone with no disorder of mood, with the ability to enjoy life, and with a rational apprecia-tion of life’s inevitable limits. But even in old age, to see nothing valuable in one’s future might be a sign of depression.The role of specialist services and cooperation 
between agencies
This topic is dealt with more fully in the succeeding chapter 
(see Chapter 8.7).
The difﬁ  culty in separating the normal from the pathological, 
and in deciding when specialist intervention is required, is reﬂ  ected

and in deciding when specialist intervention is required, is reﬂ  ected 
at a structural level in shaping the responsibilities of the different bodies involved in the welfare of older people. Help required by older people can range from the simplest of neighbourly assist ance to the full resources of specialist hospital care. As people live longer, despite some morbidity, the demand for care increases. The response to this demand is shaped by many different factors: market forces, public concern, private enterprise, voluntary or charitable groups which spring up to ﬁ  ll perceived gaps, and governments 
acting to remedy abuse or to limit demand on state-funded services. The divisions of responsibility are arbitrary, and people fall between services as often as within them. Systems change. For example, in 
the United Kingdom older people with permanent disability (espe-

cially dementia) used to be cared for in state-funded hospitals, but this care has now become the responsibility of independent-sector nursing homes, with means-tested ﬁ  nancial support from the social 
security system.
The scope of specialist services for older people extends beyond 
the treatment of established illness. They have a role in the preven-tion and early detection of illness, in supporting and educating other service providers and in collaborating with other agencies in strategic planning. This span of interest can be represented as a pyramid (Fig. 8.6.1). The peak of the pyramid represents those requiring the scarcest and most intensive specialist services, and the base represents the population at large. In the middle are the people who need day care, support at home, social support, and help in primary care.
Between a population base of, say 20 000 older people and an

Between a population base of, say 20 000 older people and an 
inpatient provision of, say 10 beds lies the range of people to whom psychiatric services can offer signiﬁ  cant help without assuming 
total responsibility for care. It is essential that the different agencies interact effectively and overlap their care, rather than leaving patients to negotiate their way from one island of provision to another.
Key components of such a ‘mixed economy of care’ should 
include:
1 A system for prompt and accurate assessment of people’s needs 
which leads to offers of appropriate help, including reassessment. 
Assessment for specialist psychiatric care should be both ‘generic’ (using the skills that all disciplines share) and speciﬁ  c (using the 
particular skills of medicine, nursing, occupational therapy, etc.).
2 A clear understanding by staff working in the various agencies

2 A clear understanding by staff working in the various agencies 
of what their tasks will be, and good training that will allow them to carry these out with conﬁ  dence and satisfaction. When non-
specialist care breaks down, it is usually because the carer do not expect to have to deal with the problem which faces them.
3 Systems ensuring that people are not obliged to make frequent 
and abrupt transfers between one setting and another as their disabilities increase. Assessment must therefore include predic-tion of future need; and each provider should offer a degree of

1575
ﬂ exibility, to encompass people who will soon need what they 
provide, and others whose needs are greater than the norm. For some people, a change of setting as their condition progresses—for example, from a sheltered ﬂ  at to care in a nursing home—will 
be inevitable, so care systems must have ways of making transi-tions as smooth as possible.
Loss of capacity and dependence on help
Mutual helpfulness is an accepted part of marital and family rela-tionships. Family members often adapt unquestioningly to an older person’s increasing dependence until the emotional pressures, or the adjustments they have to make in their day to day lives, become severe.
The ‘needs of caregivers’ are part of the currency of discussion

The ‘needs of caregivers’ are part of the currency of discussion 
amongst service providers. But people in everyday life do not nec-essarily perceive themselves that way: they think of themselves as simply participating in a normal aspect of family life. Y ounger people who have duties to their work, partner, and children—duties which conﬂ  ict with the needs of their parents—may be readier 
to seek professional help than are the ageing spouses of a failing partner. Spouses often view caring as an intrinsic part of their life-long relationship, and may resent offers from outside as an intru-sion upon their privacy.
On the other hand, relationships can have malign as well as pro-
tective aspects, and sometimes the dependent partner in a caring relationship suffers more disadvantages than beneﬁ  ts. In extreme 
cases, abuse can occur.
Abuse of older people
This is much better understood now than a few decades ago, although systematic study is difﬁ  cult because of the varieties of

This is much better understood now than a few decades ago, although systematic study is difﬁ  cult because of the varieties of 
abuse or exploitation that arise, the ambivalent relationships that surround them, and the concealment often practised by abusers and victims alike.
(14) Abuse can occur in any circumstances, any 
class, and any relationship, from blood ties and friendships to pro-fessional and commercial relations. Nevertheless pointers to risk have been identiﬁ  ed (Table 8.6.1).
Typically, the victim is disabled, often but not always with a 
dementing illness, perhaps with impaired communication, and is unrewarding to look after. Typically, the abuser is also impaired in some way, isolated from support (often by refusal rather than the 
absence of offers of help), and may abuse alcohol. There may have been a long history of ambivalence or of mutual aggression between

absence of offers of help), and may abuse alcohol. There may have been a long history of ambivalence or of mutual aggression between 
abuser and victim, or the victim’s illness may have reversed a power 
relationship that previously operated (damagingly) in the opposite direction. The intention of the abuser is sometimes clearly to do harm. In other cases the abusive behaviour seems to be an impul-
sive response to emotional pressures which the abusers are poorly 
equipped to deal with because they do not understand them prop-erly, do not know how to share the burden with others, or are over-whelmed by the patient’s need for care. The abuse may range from a single assault by a caregiver, who is immediately horriﬁ  ed by what 
he or she has done, to systematic cold-blooded persecution. Abuse may be physical, emotional, psychological, sexual, or ﬁ  nancial.
(15)
Where harm to a vulnerable person is suspected, there is an

(15)
Where harm to a vulnerable person is suspected, there is an 
obligation to report it to the appropriate authority—in the United Kingdom, the local social services. Sometimes they in turn will involve the police and a criminal prosecution may follow. But frequently the problem can be dealt with in other ways, such as 
arranging a different form of care for the vulnerable person. The emphasis will be on reducing and managing risk, and on enhancing Table 8.6.1  Some risk factors for abuse in old age
Victim Abuser Relationship
Female 
Aged over 75
Physically dependent
Cognitively impairedSocially isolated 
 (lacking external 
 support)Sensory impairment
Abusive or 
 unrewarding to 
 caregiverReady to adopt sick 
 roleFamily member in 
 caregiver role
Psychiatric history
History of abuse as a  child
Substance misuse

Abusive or 
Financial dependence  on victim
Dependence for 
 housing on victimOverburdened by 
Unsupported, or 
 rejecting supportPrevious relationship – 
 not close, 
 ambivalent, mutually 
 abusiveRole reversal
Power reversal
Lack of problem-  solving skills in the 
 relationship
Forced proximityMutual dependence
Reproduced from Fisk, J.  Abuse of the elderly. In Psychiatry in the elderly  (2nd edn.) (eds. 
R. Jacoby and C. Oppenheimer), copyright 1997, with permission from Oxford University Press.8.6 special features of psychiatric treatment for the elderly
Fig. 8.6.1 The span of old age 
psychiatry services.Direct inputRole of specialist team
Assessment at home
Caseload of community specialist worker
Support to non-specialist agencies

Response to referrals for advice
Education and informationInpatients
New cases
Attenders at
day hospitals
Attenders at social venues
Patients presenting to primary care
General population of old peopleLiving at home with support
Support
to others

SECTION 8  the psychiatry of old age 1576
the quality of life of the person concerned. Difﬁ  cult ethical issues 
arise when an elderly couple both suffer from dementia and one of them (often the husband) insists on continuing to care alone for his wife, unaware of the loss of his competence to do so. For a time, professional staff will try to support both partners in their wish to remain together at home, and to mitigate the effects of the inadequate care by the husband. But at some point the profes-sional duty may need to shift from supporting, to taking over legal responsibility for the neglected person—though the displacement of the caregiving spouse in this way is distressing for everyone 
concerned.
Ethical problems in old age psychiatry
The same classical principles of bioethics (beneficence, non-maleﬁ  cence, autonomy, and conﬁ  dentiality)
(16) apply in old age 
psychiatry as in other age groups, but with differences in empha-sis.

(17) Since older people can rarely be considered in isolation, 
ethical principles have to be applied with the whole system in mind, and professionals often have ethical obligations to more than one person at a time.
(a) Values
In old age, as in youth, we should seek to produce beneﬁ  t and not 
harm—but identifying which of these is which may be more difﬁ  -
cult in old age. Death is usually thought of as harm, but sometimes may be regarded as a blessing. Therefore it is essential to understand what the patient, rather than the professional, sees as beneﬁ  cent,

and the patient’s right to name the value that they set on something must be respected. Some older people would prefer their assets to go to their descendants rather than being spent on their own care at the end of their lives—but the state sets limits to such self-denial.
(b) Ambivalence
Impairments of thinking and communication can complicate ethically observant professional practice. People of all ages may have ambivalent feelings, or say things which seem belied by their actions, but this is particularly common among older people with cognitive impairment. Perhaps memory failure causes decisions to be swayed by feelings of the moment, so that decisions are not consistently maintained; and cognitive difﬁ  culty in marshalling 
complex information means that weighing alternative possible outcomes to a decision is much harder.
An illustration may make this clearer.
Case study:  A woman with early cognitive impairment lives alone

Case study:  A woman with early cognitive impairment lives alone 
in the house where she brought up her children. She loves her house and garden, and tells her daughters that she never wants to live anywhere else, and she is convinced that she needs no help from them. At night, however, she becomes anxious and confused, and telephones her daughters, asking them why they ‘haven’t come home yet’ and begging them not to abandon her.
Does the night or the day reveal her ‘true wishes’ better? Which 
should guide the decisions of her family, and of the professionals whose help they seek? Possibly, her considered daytime thoughts and her anxious actions at night are tapping different areas of her experience—the daytime communication reﬂ  ects her aspirations

and her lifetime self-perception, while her telephoning at night reﬂ ects the immediacy of her feelings and needs. Our duty is to give weight to both kinds of communication, helping the patient herself 
to understand what they mean, and to offer her the real-life oppor-tunity (rather than theoretical discussion) of testing out the options she needs to consider.
(c) Giving information and safeguarding information
Ethical obligations here include truth telling, giving information to patients about themselves, and protecting patients’ information from others.
‘Loss of insight’ is a feature of dementia, but good insight is also 
dependent on sound information. A person who is making signiﬁ  -

cant errors, or beginning to fail in self-care, should not be left in ignorance of what is happening to them. In fact, public knowledge nowadays about Alzheimer’s disease is so much greater that sufferers often recognize the early signs themselves. They are entitled to an open discussion with their doctors, in which full information is put before them. (Relatives often shy away from such open disclosure, although when asked in surveys what they would wish for them-selves, they tend to say that they would rather be told).
When it comes to disclosing information about a patient to the 
people involved in his or her care, the arguments are different. It is

people involved in his or her care, the arguments are different. It is 
generally accepted that better care must depend on the best infor-mation, and it is normal for information to be shared between members of a clinical team, where the members share also in the duty of conﬁ  dentiality to their patient. But in old age it is harder to 
know where to set these boundaries—both as regards information that should be protected, and as regards recognition of who is a team member. For example, senior staff in some residential homes, strictly preserving conﬁ  dentiality, may not share information about

the residents with the untrained care staff. However, if they know nothing about a resident’s former life, caregivers will tend to respond to her as ‘a bundle of needs’ rather than as a real person; and if she cannot tell her own story, others must do it for her. This is much better recognized now than it used to be, and homes may ask families to construct a diary or album of a resident’s life, with photographs, mementos, and recollections by different relatives. The diary also acts as a memory prompt and trigger for enjoyable conversations between resident and caregiver, and it creates a domain of shared information about individuals within the institution.
(d) Autonomy
Healthy people strongly value the freedom to make their own decisions, to pursue their own aims, and to determine the course of their own lives. The onset of a physical illness may constrain this freedom, but people should still have as much inﬂ  uence as possible

over decisions about their illness and its consequences.
Psychiatric disorder is different, because it may affect the powers 
by which that freedom is exercised, and may lead to decisions which would never have been made in health. From this comes the need, universally recognized although taking different legal forms in different countries, to set external controls over the decisions of people when they are mentally ill. Such legal controls are typically based on acute functional illness as the paradigm case. This gives them an ‘all or nothing’ character, envisaging hospital treatment of an illness capable of being relieved, so allowing patients to 
resume their autonomy when they recover their health.
This legal model is not really suited to cognitive impairment and its 
effect on decision-making in old age. The illness will not get better,

1577
and patients are unlikely to give (as they might with an acute illness) 
later ‘retrospective informed consent’ to the treatment. The emphasis therefore has to be much more on minimal necessary interference —
on setting up protective frameworks, in which as much autonomy as possible can be exercised; on supporting patients at home or in homely settings, rather than bringing them into a hospital where no effective treatment can be given; and on gathering the information (both from patients and from those who know them best) which will enable professional decisions to reﬂ  ect the wishes that the patient 
would have expressed, had they been able to do so.
Looking after cognitively impaired patients requires us to try

Looking after cognitively impaired patients requires us to try 
constantly to maximize the opportunity for autonomous decisions, while also being very clear when a patient lacks the capacity to engage with a more complex issue. At such times, the responsibility for the decision must be openly and seriously taken by others. Trying to circumvent the problem by concealment and persuasion is a greater affront to autonomy than is an honest explanation to the patient of the reasons why a decision has been taken out of his hands.
Medico-legal issues
‘Doctors and lawyers have common responsibilities to ensure the protection of people who are incapable of deciding matters for themselves, and to promote the choice of those who can and should regulate their own lives. The careful assessment of whether individuals have or lack capacity is essential to protect their rights’ .
(18)
The legal framework in England and Wales for both ﬁ  nancial

(18)
The legal framework in England and Wales for both ﬁ  nancial 
and welfare decision-making where capacity is in doubt has been transformed by the Mental Capacity Act 2005, which came into force in April 2007. Some general principles of the Act are worth discussing here: more detail can be found in Lush.
(19)
‘Capacity’ is a legal rather than a medical concept (see Chapter 11.1). 
Every adult is presumed to have full capacity, and a loss of capacity must be proved in relation to the particular decision being made: capacity is ‘decision-speciﬁ  c’ . For example, a person may have  the 
capacity to choose another person to act for her in the manage-ment of her affairs, while lacking  the capacity to manage those 
affairs herself. Although the ﬁ  nal decision on capacity is made by 
the courts, they look to doctors to advise on whether a mental dis-order has affected the individual’s ability to make a particular deci-sion or to carry out a speciﬁ  c task.
(a) Assessing capacity

The Act states that a person lacks capacity if ‘ . . . he is unable to 
make a decision for himself . . . because of an impairment of, or disturbance in, the functioning of the mind or brain’ . Such a person lacks capacity in relation to a particular decision if he cannot:
◆ understand the information about the decision
◆ retain the information
◆ use or weigh the information in the process of making the decision
◆ communicate the decision
The information that he must understand should include the 
consequences of deciding one way or another, and of making no decision. The information must be retained only for long enough to allow a decision to be made, therefore memory loss does not automatically remove capacity. The focus of this test of capacity is

on the process  of decision-making: the Act explicitly states that ‘a 
person is not to be treated as unable to make a decision merely because he makes an unwise decision’ .
(b) Acting on behalf of a person who lacks capacity

Anyone acting on behalf of an incapacitated person must do so in the ‘best interests’ of that person. The action or decision in ques-tion should be delayed if there is a chance that the person may regain capacity; every effort should be made to enable them to participate in the decision-making process; the decision-maker should take into account the person’s past and present wishes, beliefs, values, and feelings, especially any that had been written down when they had the capacity; the views of families, carers and anyone else interested in their welfare should be sought; and the least restrictive method for achieving the intended purpose should be chosen. The obligation to act in a person’s best interests, and the protection from legal liability if they do so without negligence, extends to anyone carrying out acts of treatment and care, such as physical assistance, doing shopping, giving medical treatment, or 
nursing care.

(c) Lasting power of attorney
A person with capacity can choose to appoint someone to act on their behalf (their ‘attorney’). The power to act continues to be 
valid even after the ‘donor’ loses capacity, provided that the docu-ment giving the power has been registered with the Public Guardian (a newly created statutory ofﬁ  ce, replacing the former Court of 
Protection). The donor can give authority to his attorney to take both ﬁ  nancial decisions and decisions relating to his health and 
welfare, provided that he is shown to lack the capacity to make those decisions himself at the relevant time. The attorney has the duty to act in accordance with the principles of the Mental Capacity Act 2005 and the guidance of its Code of Practice, and must act in the best interests of the donor.
(d) Advance decisions to refuse treatment

The Mental Capacity Act 2005 also provides a framework and safeguards for a person who wishes to decide in advance what treatments should be withheld if they lose capacity in future. Advance decisions to refuse life-sustaining treatment have to be explicit, in writing, signed, and witnessed.
(e) Driving
A common problem concerns the ability of older patients with early cognitive impairment to drive safely.
(20) Scores on simple

(20) Scores on simple 
cognitive tests (e.g. the Mini-Mental State Examination) are very poorly correlated with driving ability, except where there is severe and obvious impairment. No quick objective test of driving skills has yet been devised. A worried but competent patient can often be reassured by booking an hour with a driving instructor. Loss of the freedom to drive represents such a loss of independence and enjoyment, and such a blow to self-esteem, that advice to give up driving may be strenuously resisted. On the other hand, families and professionals are conscious of potential risks to the public even if the patient denies these risks. Legally, the position in England and Wales is straightforward: individuals have a duty to notify the Driving and Vehicle Licensing Authority ( DVLA ) if they have

an illness which might impair their ability to drive. A doctor must tell the patient who has such an illness that they are under an 8.6 special features of psychiatric treatment for the elderly

SECTION 8  the psychiatry of old age 1578
obligation to inform the DVLA; if it seems that this advice has been 
ignored, the doctor has an obligation to inform the DVLA himself—the duty of confidentiality is overruled by that requirement. Thereafter, the DVLA will arrange for the patient to receive an independent medical examination, and it is the DVLA which decides whether the driving licence should be withdrawn. If the patient fails to attend the medical examination (whether through forgetfulness or lack of insight), the licence is automatically withdrawn.
Baldwin, C. (2005). Making difﬁ  cult decisions. The experience of caring for 
someone with dementia.  Alzheimer’s Society, Gordon House, 
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Ballard, C.G., O’Brien, J., James, I., et al.  (2001).  Dementia: management 
of behavioural and psychological symptoms.  Oxford University Press, 
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8.7
The planning and organization 
of services for older adults
When does an individual become an older adult? When they show 
signs of ageing? When they retire from work? When their health becomes frail? When they feel old? When society says they are old? Any of these indicators could deﬁ  ne an ‘older person’ anywhere 
between 40 and 90 plus years! However, it was for statistical sim-plicity that many jurisdictions chose the chronological age of 65 to mark the change in status from mature adulthood to ‘older person’ , mainly to establish an age for expected retirement and entitlement to certain beneﬁ  ts, including access to geriatric health services.

When this arbitrary discriminator was instituted in the mid-twentieth century, 70 years was a good lifespan for most people. However, over the past 50 years, life expectancy steadily increased and is currently advancing at 6 weeks per annum, boosting the overall number of adults over 65 years and, particularly the over 80 
years cohort.
(1) Increasing life expectancy, due to improved health 
care and lowering birth rates, is causing worldwide ‘population ageing’ . This phenomenon will affect all health and mental health services in future years.
Already, health care resource and cost implications of population

Already, health care resource and cost implications of population 
ageing for health services are enormous. Older adults occupy about two-thirds of general hospital medical, surgical, and orthopaedic beds; they are the greatest users of primary care and prescription medicines. Internationally, late-life illness takes up a considerable proportion of government or insurance funded health care budgets. As an example of the enormous costs involved,  in 2003/2004, the 
United Kingdom’s NHS spent ar ound 43 per cent (£16.471 billion) 
of its hospital and community health services budget on people over the age of 65, and the cost of community and residential care 
for older people was 44 per cent (£7.38 billion) of all social welfare 
budgets.
(2) These figures will rise dramatically over the next 
decades.
Mental Health Services have been slow to anticipate that popula-

budgets.
decades.
tion ageing will also increase the need for psychiatric services for older people. In many areas of the world, services are scarce, sporadic, or sub-standard. Even in developed nations, there is considerable variation in availability from one area to another. In the past decade, practically all OECD countries have promoted policies of de-institutionalization and community-based care for the elderly, in response to rising cost pressures associated with population ageing, plus a requirement to improve satisfaction for increasingly knowledgeable and assertive consumers, by providing 
better quality in all health services for older adults, including mental health.
(3)
The need for services for older adults

(3)
Whilst most people aspire to longevity, it can be a mixed blessing. Living longer increases risk of developing chronic degenerative diseases of body and brain, which can precipitate mental illness, possibly for the ﬁ  rst time in life. Psyc hiatry services for older adults 
see a full range of new and chronic psychiatric disorders. However, the commonest new threats to mental health in late life are affective disorders and dementia.
(4) Healthy, community-dwelling older adults 
are generally resilient, with a prevalence of major depressive illness of about 3 per cent, but studies of people in residential care ﬁ  nd 
signiﬁ  cant depressive symptoms in 14–42 per cent,
(5) and in popu-
lations over 80 years, about 40 per cent.(6) Depression occurs in 
15 to 40 per cent of medical inpatients(7) and in approximately

15 to 40 per cent of medical inpatients(7) and in approximately 
35.9 per cent of patients in geriatric rehabilitation units.(8) Among 
the many aetiological contributors to me ntal health problems in 
late life, physical illness and poor health are major risk factors, particularly for depression,
(9) the risk increasing with disability.(10)
Co-morbid physical disorders can mask depression or impede management with psychotropic medications. Although, pure anxiety disorders reduce in late life to about 1 per cent in community-dwelling older adults, anxiety co-morbid with other psychiatric disorders, particularly depression, is more common at approxi-mately 4 per cent. Older people with anxiety disorders are high users of health care resources and may initially present with physical symptoms.
(11) Affective disorders are often multi-dimensional,

(11) Affective disorders are often multi-dimensional, 
their treatment complicated, and frequently, they need joint management with geriatric colleagues.
Dementia affects 5–7 per cent of people at 65 and 20 per cent 
of those over age 80 years. By 2040, the number of people with the disorder will double in the developed countries of Europe and North America.
(12) Older adults with dementia are an exemplar of 
consumers who require multi-disciplinary management. While geriatricians manage the majority of patients, those who exhibit 
behavioural and psychological symptoms of dementia (BPSD), 
approximately one-third, do best with additional specialist psychiatric

SECTION 8  the psychiatry of old age 1580
expertise and management.(13) People with dementia can live for 
many years as their disorder progresses, requiring increasing levels of support from family, social workers, nurses, residential care providers, and other community health care workers in addition to psychiatry services.
Why are specialist services required?
As indicated above, mentally or physically frail older adults have complex needs and frequently require a broad, multi-disciplinary approach in several domains, (a domain being a broad area of spe-cialist services i.e. mental health, geriatrics, primary care, social ser-vices, etc.). This can be difﬁ  cult to achieve if provision is by

disjointed services. In many places in the world, lack of specialist services requires generic mental health services to treat older adults with dementia, depression, or other mental illnesses but this prac-tice risks medical needs being unnoticed, or unappreciated. Frail older adults can ﬁ  nd the experience of inpatient care in units with 
younger psychotic patients frightening and unacceptable. There are also different perspectives for working-age and geriatric psychiatry. Many working-age services promote a recovery model whereas care of older adults focuses on maintaining function, improving quality 
of life and paying more attention to the spiritual, environmental, 
and social inﬂ  uences on mental health. In addition, there is greater

and social inﬂ  uences on mental health. In addition, there is greater 
need to involve the social and family network of mentally frail elderly people than there is for working-age adults. For older adults, specialist services, with close collaboration with geriatricians and other geriatric providers, are preferred for optimal management.
Principles of good service delivery 
for older adults
Optimal service delivery starts by establishing the principles that 
services wish to adopt. These should govern the ethos of service delivery. For the World Health Organization ( WHO), the mnemonic 
CARITAS (Latin for Compassion) summarizes a global consensus on speciﬁ  c values required for good service delivery for psychiatry 
of old age.
(14) These principles, championed over many years by 
many international pioneers of mental health services for older adults, assert that optimal services are:
◆ Comprehensive

of old age.
 They take all aspects of the patient’s physical, psychological, and 
social needs and wishes into account i.e. are patient-centred .
◆ Accessible
 They minimize the geographical, cultural, ﬁ  nancial, political, 
and linguistic obstacles to obtaining care.
◆ Responsive
 They act promptly and appropriately to a wide variety of patient 
needs.
◆ Individualized
 They focus on each person in her/his family and community 
context aiming, wherever possible, to maintain and support the person within her/his home environment.
◆ Transdisciplinary
 They optimize the contributions of people with a range of per-
sonal and professional skills and facilitate collaboration with vol-untary and other agencies.◆ Accountable
 They accept responsibility for assuring the quality of the service

 They accept responsibility for assuring the quality of the service 
delivered, monitoring this in partnership with patients and their 
families. They are ethically and culturally sensitive.
◆ Systemic
 They work ﬂ  exibly with all available services to ensure continuity 
of care.
Summarizing, good services provide patient-centred  care with 
easy access to a comprehensive range of services  delivered by multi-
disciplinary personnel  working in a collaborative, responsive, respectful, 
and accountable  way.
Patient-centred care
The UK National Frameworks for Older People(15) and most OECD

The UK National Frameworks for Older People(15) and most OECD 
health administrations promote patient-centered care as a major means of improving quality of services and consumer satisfaction. Whilst most health professionals believe that they already practice patient-centred care, many patients would not agree. Predominantly, health systems for older people, particularly hospital-based, are far from patient-centered, being mostly organized around clinician or administrative requirements rather than patient needs. Patients encounter rigid appointment times, lack of evening or night services, inﬂ  exible boundaries between departments, inconvenient

visiting hours, limited or expensive parking, and silo’d funding streams. Access or contact processes are obscure or difficult, information is inadequate, multiple assessments take place, and poor coordination between providers leads to treatment omissions 
or errors. Notably, older adults and their caregivers consider having multiple referrals to different specialists or providers and frequently repeating the same history to be a waste of time and 
resources.
(16)
Consumer appraisals of their experience of services often result 
in common themes. Many experience poor communication—provider to patient, provider to caregiver, and provider to provider. Another common topic is lack of ﬂ  exibility in developing manage-

ment plans capable of involving several domains and dimensions of care (a dimension is a subset of a specialist domain, i.e. depression, dementia, continence, or mobility). As many elderly people have dif-ﬁ culties with mobility, or live far from services, transportation is 
another major issue.
In contrast, patient-centered services emphasize smoothing 
the progress of the patient ‘journey’ through the health system, eliminating duplication, matching care plans to patient needs, and generally making a demanding experience easier for the patient and their family. Unsurprisingly, the concept is appealing to patients and families. Increasingly, consumers, and their advocates, want to 
contribute to service planning, delivery, and evaluation.
(17) So,

(17) So, 
what do older people want from their health care providers? Older people value their independence and being involved in the decision-making for their own care plans. Most want to remain in their own homes for as long as possible, but if that is detrimental for them, they want the right to relinquish decision-making, in various degrees, to other parties such as family members or their clinicians. They expect providers to treat them as an individual, to preserve their dignity, and to elicit and respect their preferences. Above all, they wish to be appropriately informed.
(18) These desires are 
appropriate to all health care delivery for older adults, not just mental health. As most of us hope to grow old, we can empathize

1581
with these wishes. Perhaps we need to remember that in planning 
and organizing services for older adults, we are potentially design-ing them for ourselves. The quality of care required is what we would be happy with, if we ever become clients.
Comprehensive and integrated services
Patient-centered care is more achievable with comprehensive or integrated services. The terms comprehensive and integrated are not interchangeable. A comprehensive service is one with a full range of inpatient and community services available within the same domain. An integrated service is one with a single point of entry capable of providing care plans that incorporate interven-tions and support in multiple domains and speciﬁ  c dimensions of 
care. Integrated services are characterized by a single point of entry, case management, geriatric, psychogeriatric and social assessments, and have multi-disciplinary teams.
(3) They should have a seamless

(3) They should have a seamless 
joining together of the various components of service, encompass-ing ‘systemness’ without diminishing component part identities.
(19)
Integration of different organizations is much easier if there are common administrative processes and ﬁ  nancial systems. However, 
many mental health organizations have reporting and funding structures separate from other older adults’ services (e.g. The Mental Health Trusts in the United Kingdom). Quasi-integration can be achieved by building effective functional  links with a wide 
variety of health care professionals outside mental health e.g. pri-mary care, geriatrics, acute medical and surgical care, social care, community health care, and non-clinical resources. For these col-laborations to work, it is essential that bureaucratic processes enable easy transfer of funding and information across different entities and do not thwart clinicians’ efforts to implement care plans for patients.

Integrated services are potentially more efﬁ  cient as they should 
reduce duplication of assessments or investigations and service gaps. Currently, the majority of well-established services for older adults provide comprehensive rather than integrated services,
(20)
the latter being more ideology than practice, although this might be slowly changing. Research indicates that integrated care can delay institutionalization, reduce costs, and has beneﬁ  ts in con-
sumer satisfaction
(3) but is insufﬁ  cient, as yet, to demonstrate that 
integrated services are more effective in achieving better health outcomes.
(a) The place of the common geriatric assessment (CGA)

An important tool for assisting integration is the common geriatric assessment (CGA). Different disciplines all have their own styles and foci for assessment but, despite individual differences, it is useful to have some common information for all teams and multi-disciplinary groups, regardless of who takes the main responsibility for the patient.
(21) Advocacy for the comprehensive geriatric assess-
ment (CGA) covering all the main domains and dimensions of physical illness, mental health, disability, and social assessment, is increasing internationally, notwithstanding a lack of research on their effectiveness in improving health outcomes. They aim to save a patient from multiple repetitions of the same information.
(16)

(16)
T o be useful, CGAs require personnel to work across professional and agency barriers, which can have beneﬁ  ts in creating relationships 
with allied colleagues, essential for developing integrated services. There needs to be agreement amongst the providers as to the appli-cability of the information required, agreed processes by which the CGA generates onward referral to the appropriate domains of care and procedures for updating and review. In some jurisdictions, (e.g. 
United Kingdom) CGAs or single assessment processes (SAPs) are mandatory for all older adults’ services, in others, i.e. New Zealand and Australia, they are being trialed with a view to future obligatory use. SAPs and CGAs vary in their comprehensiveness and can aim at different levels, e.g. screening, proactive assessment, primary care, or secondary care services. They provide useful background infor-mation common to a range of providers but are not a substitute for specialized clinical assessment.

(b)  The ‘core business’ of mental health services for 
older adults
Irrespective of whether a mental health service for older adults is part 
of a comprehensive or integrated system, their ‘core business ’ is the:
◆ Diagnosis and management of new cases of mental illness arising 
in late life, often associated with the ageing process.
◆ Treatment of mental illness complicating physical illness and disability.
◆ Management of older adults with long-term mental illness com-plicated by ageing.
◆ Education and support for caregivers of older adults with mental illness.
Most psychiatry for older adults is about the management 
of chronic illness and care, rather than cure, is usually the main priority. An adaptation of the 5As model for patient-centred chronic illness management
(22) is useful to describe the ‘core tasks ’
of patient-centered psychiatry of old age. They are:
◆ Assessment of multiple care needs
◆ Advice on diagnosis and options for management

◆ Agreement with patient and caregiver on a care plan
◆ Assistance with implementation of care plan
◆ Assertive follow-up when needed
The ‘core areas of expertise ’ for specialist services for older adults 
are the:
◆ Treatment of affective and psychotic disorders in late life
◆ Assessment of neurocognitive disorders and the management of the behavioural and psychological symptoms of dementia (BPSD)
◆ Rehabilitation of long-standing, chronic psychiatric disorders in patients whose disorder is complicated by physical illness or ageing
◆ Management of delirium in medically ill or complicating dementia
◆ Liaison with families, caregivers, and community providers
Core components of psychogeriatric service 
delivery
The evidence base for the ‘core components’

delivery
Working with mentally ill older adults involves a variety of loca-
tions i.e. the patient’s own residence, medical and surgical wards in a general hospital, psychiatry inpatient facilities, residential care facilities, outpatient clinics, outreach clinics, geriatric rehabilitation 8.7 the planning and organization of services for older adults

SECTION 8  the psychiatry of old age 1582
units, or day hospitals. Several models of services for older adults 
have evolved over the past 30 or 40 years, shaping a degree of accord amongst clinicians on what are ‘core components’ . The evidence for these has been systematically reviewed by Draper and Low.
(23)
(See Table 8.7.1.)
Community old age psychiatry services
The lynchpin of geriatric psychiatry services is the community-
based assessment and case management team. The community team model originated from the closure of the mental hospitals and the move into community-care in the 1980–90s. Their focus is domiciliary assessment and management. This offers the clinician 
opportunities to observe patients in their own environment, and

opportunities to observe patients in their own environment, and 
promotes optimal cognitive functioning by decreasing stress for the individual. Home assessment avoids the sometimes-perceived stigma of attending a psychiatric clinic and eliminates transporta-tion difﬁ  culties, as well as allowing ready access to family members 
or other caregivers. Treatment for most patients can take place at their residence (own home or nursing home), reducing reliance on inpatient or residential care. The model has proven to be efﬁ  cient 
and highly acceptable to consumers and caregivers.
A typical multi-disciplinary team consists of at least one psychia-

trist, psychiatric nurses, clinical psychologists, social workers, occu-pational, and other therapists plus support and administration staff. A psychiatrist traditionally leads a multi-disciplinary team but not necessarily so. As a whole, the team should be able to address the biopsychosocial, therapeutic, and psychoeducational requirements of a wide range of disorders and intervention 
settings. T eam members case-manage depending upon their own special skills and expertise. Working collaboratively, with appropri-ate training, good supervision, and well-designed protocols and communication systems enhances the multi-disciplinary team. Some of the most effective teams are ‘interdisciplinary’ who devel-op ﬂ exible working patterns characterized by a non-hierarchical

structure, and shared decision-making. They facilitate lateral communication between team members, and free exchange of ideas to develop optimal treatment and support management plans as a group. The evidence for community-delivered specialized multi- or interdisciplinary psychogeriatric assessment and man-agement teams is strong and indicates consistently better outcomes than ‘usual care’ of primary care or generic mental health management.
Inpatient units

Inpatient units vary from the specialized older person’s assessment, treatment, and rehabilitation (ATR) unit, similar to their geriatric counterparts, to dedicated beds in geriatric wards, or donated beds in working-age mental health units. Preferably, a specialized inpatient unit is purpose built or has the functionality to separate patients with functional and organic disorders, as each group has different clinical features, nursing needs, disabilities, and requirements for care plans. The evidence for specialized inpatient psychogeriatric units is positive but as there have been few random controlled trials (RCTs), it is less robust than the evidence for 
Table 8.7.1  Level of evidence and study qualities for areas of service delivery
Area No. of studies 
reviewedNo. of controlled 
trialsQuality range,* range 
(low) 0–1 (high)Mean rating of 
qualityLevel of evidence of effectiveness

Psychogeriatric day hospitals 10 0 0.43–0.82 0.57 Level IV (particularly depression)
Community old age psychiatry 
services24 7 0.79–0.94 0.87 Level I for multi-disciplinary psychogeriatric 
teams, level IV for adult psychiatry teams
Integrated hospital and 
community-care4 2 0.71–0.82 0.76 Level II for psychogeriatric services 
post-discharge care, no evidence for geriatric medical services (level I)
Primary care collaborations 3 2 0.89–0.94 0.92 Level II
Older people in general adult 
psychiatric wards6 0 0.51–0.67 0.59 Level IV
Acute psychogeriatric wards 23 0 0.43–0.78 0.61 Level III-2
Hospital medical services 6 2 0.82–0.90 0.89 Level II for prevention of delirium without 
dementia, no evidence for other mental 
health outcomes (level 1)
Combined psychogeriatric and 
medical wards3 0 0.52–0.53 0.52 Level IV

Hospital-based CL psychogeriatric 
service delivery7 3 0.62–0.90 0.79 Level II effectiveness for reducing costs and 
length of stay
Long-term psychogeriatric care 11 0 0.58–0.71 0.66 Level III-2Psychogeriatric outreach to 
long-term care8 6 0.73–0.95 0.84 Level II for liaison style outreach services, 
Level III-2 for consultation style
Overall 108 25 0.62–0.95** 0.85**
*If ≥2 controlled trials in service area, quality range reported for RCTs only, otherwise reported for all studies. **overall mean a nd range reported for controlled trials only.
(Reproduced from Draper, B. Melding, P . and Brodaty, H. (2005) Psychogeriatric Services Delivery: An international perspective,  copyright 2005, with permission from Oxford University Press.)

1583
community teams. Nevertheless, what evidence exists points 
to specialized psychogeriatric units having better outcomes for psychogeriatric patients than working-age mental health, or geriat-ric medical units.
(23) Scientiﬁ  c evaluation of combined psychogeri-
atric and geriatric medical wards is inadequate but expert clinical 
opinion considers them useful in the management of co-morbid medical and psychiatric illness.
Consultation and liaison
Hospital-based consultation and liaison (CL) services are important components because of the high number of mental disorders in the physically ill, general hospital populations. However, while the evidence is relatively good for CL outcomes such as hospital stays and costs, it is only modestly positive for mental health out-
comes.
(24) Notwithstanding, in recent years, older adults’ CL

comes.
(24) Notwithstanding, in recent years, older adults’ CL 
services have outreached from the general hospital to provider organizations in the community. The evidence for these liaison services, usually provided by community teams to psychogeriatric long-term care facilities and voluntary organizations, is relatively good.
(23)
Day Hospitals
Day Hospitals, originally attached to the old psychiatric institutions, have mostly devolved into community facilities and many United Kingdom psychiatrists of old age consider them indispensable.
(25)
Specialist day hospitals provide care for people with moderate and severe needs, including people w ith functional mental illnesses such 
as depression, anxiety, and schizophrenia, who may need speciﬁ  c 
support with daily activit ies and people with moderate to severe 
dementia. The Day Hospital allows hospital level treatment while allowing patients to remain living in their own residence. The

dementia. The Day Hospital allows hospital level treatment while allowing patients to remain living in their own residence. The 
evidence for their effectiveness, while positive, is sparse. As they are less common, they are not as revered in other parts of the world as much as they are in the United Kingdom. Day Hospitals need to be differentiated from Day Centres, managed by the voluntary or welfare sectors, which usefully provide social activities to keep the patient involved with their community and much needed respite for caregivers.
Residential care
An elderly person unable to support themselves in their own home needing daytime or 24 h supervision requires a resident caregiver or residential care facility. A community may have a range of resi-dential care facilities managed by a variety of agencies such as local authorities, voluntary organizations, for-proﬁ  t or not-for-proﬁ  t

religious and welfare organizations in the independent sector. These non-government organizations (NGOs) provide care homes for older adults who need support because of physical or mental frailty but not to the extent of requiring hospital level care. Many of the residents have some cognitive impairment and, unsurpris-ingly, a relatively high number of patients have complicating depression and/or psychosis. Residential care homes vary mark-
edly in their ability to support older adults with mental health 
problems. Evidence from The Netherlands
(26) and Australia(27)
indicates that mental health enhanced care in the form of regular psychogeriatric team liaison to these residential facilities has ben-eﬁ cial outcomes for patients for example less inpatient stays, less 
psychotropic medication, and improvement in depression and psychosis.Long-term care

Progressive de-institutionalization since the 1980s saw the transfer of many long-stay, public sector beds, for patients with dementia or intractable mental illness, to community-based nursing homes or hospitals. These facilities were generally smaller, more home-like and provided additional activities for the residents than traditional long-term care did. The change required many old age psychiatry services to collaborate with independent sector stakeholders and evolve outreach and liaison models of care with the new long-term residential care facilities. This paradigm shift for service delivery was beneﬁ  cial for patient outcomes.
(23)
Disturbed behaviour resulting from dementia (BPSD) can be

(23)
Disturbed behaviour resulting from dementia (BPSD) can be 
severe enough for patients to need Specialized Care Units (SCUs). Examples are in Italy, France (CANTOUs), Tasmania (ADARDS unit), and London (Domus units). Such units have a small number of beds, well-trained staff with high staff to patient ratios and access to ongoing specialized psychogeriatric team care. When compared with traditional psychogeriatric ward patients, unsurprisingly, those in a specialized care unit, show improvements in cognition, self-cares, activity participation, and behaviour. The key elements to success appear to be training staff to anticipate and recognize mental health problems and close liaison with specialist mental health teams.
Respite care
The community-care model relies on family, rather than profession-als to attend to most of the needs of a mentally frail, elderly person. This is demanding, difﬁ  cult work for caregivers who usually have

other responsibilities of family, home, and jobs. The main focus of respite care is to give lay caregivers a break from caring every few weeks, so they may continue to provide care and thus delay the need for permanent nursing home care as long as possible. Respite can be in the patient’s own home, by providing a ‘live-in’ profes-sional caregiver, or in hospital or a residential care facility for a week or two, every couple of months, allowing the family caregiver to take a holiday. Whilst seeming an admirable concept, the effec-tiveness of respite care is doubtful and there is little evidence that it has a signiﬁ  cant effect on caregivers’ burden, psychiatric status or 
physical health, or on patients’ cognition, function, physical health, or rate of institutionalization.
(28) Respite care, even when available, 
may be poorly utilized. Caregiver barriers to using respite care include guilt, ﬁ  nancial reasons, cultural attitudes, and fear of stigma.

may be poorly utilized. Caregiver barriers to using respite care include guilt, ﬁ  nancial reasons, cultural attitudes, and fear of stigma. 
Access barriers include unavailability, lack of publicity about ser-vices, long waiting lists, and poor identiﬁ  cation of at-risk caregivers. 
Patient barriers include severe problem behaviours, immobility, incontinence, wandering, and inability to communicate.
(29)
Primary care collaborations
Despite older adults forming the majority of patients seen by gen-eral practitioners (GPs), they detect and treat less than half the number of older adults with mental disorders.
(30) Short consulta-

tion times, with a concentration on physical symptoms, with few patients presenting explicitly with mental health complaints, plus a reluctance of older adults, especially men, to express psychological distress to their GP , leads to under-recognition of mental disorders in older adults. Depression may be erroneously attributed to loneliness or ageing and early dementia overlooked. Primary care practitioners also make fewer decisions to treat or refer patients 8.7 the planning and organization of services for older adults

SECTION 8  the psychiatry of old age 1584
to specialist services and often preferred to monitor, or defer 
decisions.(31)
Mere cooperation between mental health services and primary 
care seems insufﬁ  cient to improve matters. Collaborations such as 
mental health enhanced primary care looks more promising. 
Education of primary care nurses in recognition of mental disor-ders and use of screening instruments might be useful to improve identiﬁ  cation of mental disorders.
(31) Even better is the idea of

(31) Even better is the idea of 
‘embedding’ nurses, who have the skills necessary to identify health problems and coordinate care for older adults, into primary care practices. One experimental scheme in New Zealand, ‘The Coordinators of Services for the Elderly’ (COSE project) works within a primary care small group of practices to coordinate care of the practices’ elderly patients across health, mental health, community, and accident services. An RCT of the COSE project over usual care signiﬁ  cantly demonstrated that patients in the 
COSE arm were less likely to be hospitalized, their residential care was delayed and morbidity reduced.
(32)
The primary care physician is crucial to patient care from start to 
ﬁ nish, not only in identifying people who are at risk but also for

(32)
ﬁ nish, not only in identifying people who are at risk but also for 
any post hospital discharge care as the majority of patients seen by specialist services eventually return to primary care for ongoing management, in conjunction with their family caregivers. Even if patients or their caregivers can self-refer to secondary services, it is important not to bypass the general practitioner, who has awareness of the patient’s overall health care and context.
Special components of services
Memory clinics
The substantial growth in numbers of memory clinics, over the past 10–15 years, was stimulated by the licensing of cholinesterase inhibitor drugs for Alzheimer’s disease.
(33) Memory clinics offer a

(33) Memory clinics offer a 
range of services from assessment of cognition to specialized treat-ment of memory problems. Dedicated memory services can improve diagnostic expertise and lessen stigma for the patient. Usefully, they often focus on education of patients and caregivers as well as monitoring medications. However, the concept of a ‘memo-ry clinic’ ﬂ  ies in the face of the trend towards community-based 
services and integration with local services. Furthermore, the inter-vention base is often very narrow. Very few studies provide any evi-dence of increased mental health gain over other psycho geriatric services, but there is some evidence that the attention, communica-tion, and counselling offered increases consumer satisfaction.
(34)
Older adults with intellectual handicap

(34)
People with intellectual handicap are also living longer and they are at particular risk for developing dementia. Over 55 per cent of people with Down’s syndrome between the ages of 60–70 have Alzheimer type dementia, which often begins to emerge in midlife rather than old age. Consequently, the intellectually handicapped older person has complex care needs that require dementia, mental health, and learning disability services to work together 
assiduously.
(2)
Older prisoners
An often forgotten group is ageing prisoners, who are also increas-ing in number. Older prisoners have increased risk for depression and other mental health problems. Long-serving older prisoners 
may develop dementia and require the special challenge of care delivery whilst incarcerated. Specialist services for older prisoners are scarce and, if available, usually provided by visiting community assessment and treatment services in conjunction w ith local fo rensic

psychiatry services.
Younger people with dementia
Early onset dementia is fortunately rare but when it occurs, it is dev-astating. The patients usually have family responsibilities with young children, jobs, and ﬁ  nancial commitments. Early onset dementia 
usually has a more accelerated course and genetically related family members may be concerned for themselves or their offspring. Diagnosis is often delayed for younger people so considerable dis-tress and problems have usually built up before they reach services. Their management needs may also be different as they are usually physically ﬁ  tter and they may require more structured activities 
than their older counterparts do, but need similar levels of supervi-sion. Appropriate services for younger people who develop demen-tia are often scarce and the patients may fall into an under-resourced gap between working-age and older adults’ services.
Academic units

Although there has been a growth in the number of geriatric psychiatry academic units and positions worldwide, they are still under-represented in universities worldwide. They are important providers of under and postgraduate teaching and research.
Planning to commissioning
Commissioning is ‘the process of specifying, securing, and moni-toring services to meet the needs of a population at a strategic level’ .
(2) Proposed services require a ‘business case’ with the place 
of an intended service clearly demonstrated in the overall schemata of health provision for a population. Demonstration of the need for services and projections of likely demand is necessary and the chief scientiﬁ  c tools available to identify these are epidemiology, 
demography, and utilization studies.
Epidemiology predicts the likely problems in a population and

Epidemiology predicts the likely problems in a population and 
demography the characteristics of the population that could increase risk. The older the population, the more likely it will have a high prevalence of dementia requiring services. An important demographic to consider when planning services is the socio-economic status of a population. Low socio-economic status increases the likelihood of poor physical health, poor functionality and deprivation causes stress, leading to poverty of control over 
one’s life, low self-esteem, anxiety, insecurity, and depression.
(35)
Also important is the number of immigrant residents. Ethnic elders 
are more likely to have earlier social disadvantage compounding in later life into a multiple jeopardy of social disadvantage, poorer physical health, and mental health problems.
(36)
Whilst epidemiological studies may predict potential need,

(36)
Whilst epidemiological studies may predict potential need, 
and demographics highlight areas of possible risk, not all people with problems will demand services. Demand or utilization is considerably less than the potential need as predicted from the demographical and epidemiological data. International research consistently shows similar demand patterns. About half of identi-ﬁ ed patients obtain treatment from a health care provider. Only 
10–16 per cent reaches specialist mental health services, and

1585
primary care treats about 30–40 per cent. For older adults utiliza-
tion is even less than for working-age adults.(37) Stigma can have a 
detrimental effect on willingness to access services(38) as may cul-
tural barriers.(36) For individuals, utilization of mental health ser-
vices is more likely if the disorder is severe, is adversely affecting the 
family or social network, or the patient is female.
Services are usually commissioned based on expected demand 
rather than predicted need. Demand often increases, outstripping supply once services are available and information about them per-meates into the community. Resource review on a regular basis as demand rises is necessary.
Commissioning new or revised services involves stocktaking of

Commissioning new or revised services involves stocktaking of 
available resources for older adults. Often these are inequitable, with urban areas enjoying a range of services that rural areas lack. Despite unique individualities of different countries of the world, some characteristics tend to be true of all rural communities. They tend to be older and poorer than urban populations with a higher percentage of females.
(39) Stoical older adults living in rural areas 
have a high tolerance of distress and are often reluctant to seek help from mental health services.
(40) Consequently, rural populations 
are even more vulnerable for late-life mental health disorders, yet outreach services are usually infrequent, and primary care limited. Some countries with very large rural areas, for example United States, Canada, Africa, Australia, and New Zealand commission novel methods of outreach, such as ﬂ  ying doctor services.
Ideally, service planning should be in conjunction with key stake-

holders, that is consumers, other geriatric services and providers, including NGOs. For optimal patient-centred mental health care for older adults to be effective, individual specialist hospital services need to work with general practitioners and other community providers. Attention to administrative pathways and funding struc-tures that promote collaboration between providers is important. Commissioning strategies that prop ose integration of existing 
services need to recognize that, whilst the end result may be beneﬁ  -
cial to patients, the process will cause enormous upheaval and 
distress among the workforce involved, particularly if there is decommissioning or amalgamation of duplicate services.
Service development is contingent on there being a skilled, educated

Service development is contingent on there being a skilled, educated 
workforce. A development plan needs to consider the specialist disciplines required, based on expected case mix and work loads, staff availability, recruitment and retention, morale, job satisfac-tion, and very importantly, training issues. Clinical services have important roles in teaching and training ongoing professional development and in clinical evaluation, and systems research. These tasks can also be important means of cross-fertilization, dis-semination of ideas between related services, teams, and disciplines. Involvement of different disciplines in undergraduate or postgrad-uate teaching programmes including psychiatry trainees can be useful for disseminating a broader perspective to prospective health 
professionals intending to work with older adults.

A vital aspect of commissioning is monitoring, that is, the methods 
of service review and evaluation. This is important for continuing quality initiatives and research but also to provide evidence for review and future commissioning of even better services.
Worldwide, population ageing is driving the development of men-tal health services for older adults. Finite resources, burgeoning costs, expanding therapeutic repertoires, and increasing consumer 
interest in involvement in health care is challenging health organi-zations to develop effective, efficient, and economic patient-centred services for older adults. Fundamentally, the quality of services is dependent on health personnel working with their patients and other providers, towards shared aims of improving health out-comes and quality of life. Clinicians’ adaptability, ﬂ  exibility, respon-

siveness, availability for patients, and willingness to collaborate are the keys to success in developing future services for older adults.
Draper, B., Melding, P ., and Brodaty, H. (eds.) (2005). Psychogeriatric service 
delivery: an international perspective . Oxford University Press, Oxford, 
New Y ork.
Department of Health and Care Services Improvement Partnership. (2005). 
Everybody’s business. Integrated mental health services for older adults: a service development guide . www.everybody’sbusiness.org.uk
World Health Organization. (1997). Organization of the care and the 
psychiatry of the elderly . World Health Organization, Geneva.
Melding, P . and Draper, B. (eds.) (2001). Consultation liaison geriatric 
psychiatry . Oxford University Press, Oxford, New Y ork.
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Psychogeriatric service delivery , pp. 4–13. Oxford University Press, 
Oxford, New Y ork.

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(2005). Everybody’s business. Integrated mental health services for older 
adults: a service development guide . Older people and disability division, 
Directorate of Care Services, Department of Health, London.
 3. Johri, M., Beland, F., and Bergman, H. (2003). International 
experiments in integrated care for the elderly: a synthesis of the evidence. International Journal of Geriatric Psychiatry ,18(3), 222–35.
 4. Riedel-Heller, S.G., Busse, A., and Angermeyer, M.C. (2006). The 
state of mental health in old-age across the ‘old’ European Union—a systematic review. Acta Psychiatrica Scandinavica ,113(5), 388–401.
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populations of elderly: a review. Acta Psychiatrica Scandinavica ,

5. Djernes, J.K. (2006). Prevalence and predictors of depression in 
113(5), 372–87.
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correlates of depression in the oldest old: the OCTO study. Aging & 
Mental Health ,3(2), 119–28.
 7. Gareri, P ., Ruotolo, G., Curcio, M., et al.  (2001). Prevalence of 
depression in medically hospitalized elderly patients. Archives of 
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in a rehabilitation unit for older adults. Postgraduate Medical Journal ,
76(893), 153–6.
 9. Cole, M.G. and Dendukuri, N. (2003). Risk factors for depression 
among elderly community subjects: a systematic review and meta-analysis. The American Journal of Psychiatry ,160(6), 1147–56.
10. Braam, A.W., Prince, M.J., Beekman, A.T.F., et al. (2005). Physical

10. Braam, A.W., Prince, M.J., Beekman, A.T.F., et al. (2005). Physical 
health and depressive symptoms in older Europeans: results from EURODEP . The British Journal of Psychiatry ,187(1), 35–42.
11. Flint, A.J. (2005). Generalised anxiety disorder in elderly patients: 
epidemiology, diagnosis and treatment options. Drugs & Aging ,
22(2), 101–14.
12. Ferri, C., Prince, M., Brayne, C., et al. (2005). Global prevalence of 
dementia: a Delphi consensus study. Lancet ,366(9503), 2112–17.
13. Brodaty, H., Draper, B., and Low, L.F. (2003). Behavioural and 
psychological symptoms of dementia: a seven-tiered model of service delivery. Medical Journal of Australia ,178(5), 231–4.8.7 the planning and organization of services for older adults

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14. World Health Organization. (1997). Organization of the care and the 
15. Department of Health. (2001). National service framework for older 
people .
16. Stevenson, J. (1999). Comprehensive assessment of older people. Kings 
fund rehabilitation programme. Developing rehabilitation opportunities for older people . Kings Fund, London.
17. Dening, T. and Lawton, C. (1998). The role of carers in evaluating 
mental health services for older people. International Journal of 
Geriatric Psychiatry ,13(12), 863–70.
18. Robb, G. and Seddon, M. (2006). Quality improvement in New Zealand 
healthcare. Part 6: keeping the patient front and centre to improve healthcare quality. The New Zealand Medical Journal ,119(1242), 
U2174.
19. Melding, P . (2005). Integrating service delivery and quality of care. In 
Psychogeriatric service delivery  (eds. B. Draper, P . Melding, and

U2174.
Psychogeriatric service delivery  (eds. B. Draper, P . Melding, and 
H. Brodaty), pp. 251–80. Oxford University Press, Oxford, New Y ork.
20. Challis, D., Reilly, S., Hughes, J., et al.  (2002). Policy, organisation 
and practice of specialist old age psychiatry in England. International 
Journal of Geriatric Psychiatry ,17(11), 1018–26.
21. Stevenson, J. (1999). Comprehensive assessment of older people. Kings 
22. Sheridan, S.L., Harris, R.P ., and Woolf, S.H.A. (2004). Shared decision 
making about screening and chemoprevention: a suggested approach from the U.S. preventive services task force. American Journal of 
Preventive Medicine ,26(1), 56–66.
23. Draper, B., and Low, L.F. (2005). Evidenced-based psychogeriatric

23. Draper, B., and Low, L.F. (2005). Evidenced-based psychogeriatric 
service delivery.  In Psychogeriatric service delivery: an international 
perspective  (eds. B. Draper, P . Melding, and H. Brodaty), pp. 75–122. 
Oxford University Press, Oxford, New Y ork.
24. Draper, B. (2001). Consultation liaison geriatric psychiatry. In Geriatric 
consultation liaison psychiatry  (eds. P . Melding and B. Draper), 
pp. 3–34. Oxford University Press, Oxford, New Y ork.
25. Hoe, J., Ashaye, K., and Orrell, M. (2005). Don’t seize the day hospital! 
Recent research on the effectiveness of day hospitals for older people 
with mental health problems. International Journal of Geriatric 
Psychiatry ,20(7), 694–8.
26. Depla, M., Pols, J., De Lange, J., et al.  (2003). Integrating mental health

26. Depla, M., Pols, J., De Lange, J., et al.  (2003). Integrating mental health 
care into residential homes for the elderly: an analysis of six Dutch programs for older people with severe and persistent mental illness. Journal of the American Geriatrics Society ,51(9), 1275–9.
27. Brodaty, H., Draper, B., Millar, J., et al. (2003). Randomized controlled 
trial of different models of care for nursing home residents with dementia complicated by depression or psychosis. The Journal of 
Clinical Psychiatry ,64(1), 63–72.
28. Flint, A. (1995). Effects of respite care on patients with dementia and 
their caregivers. International Psychogeriatrics ,7, 505–17.
29. Brodaty, H. and Gresham, M. (1992). Prescribing residential care for 
dementia- effects, side-effects, indications and dosage. International 
Journal of Geriatric Psychiatry ,7, 357–62.

30. Speer, D. and Schneider, M. (2003). Mental health needs of older 
adults and primary care: opportunity for interdisciplinary geriatric 
team practice. Clinical Psychology: Science and Practice ,10(1), 
85–101.
31. Watts, S.C., Bhutani, G.E., Stout, I.H., et al. (2002). Mental health 
in older adult recipients of primary care services: is depression the 
key issue? Identiﬁ  cation, treatment and the general practitioner. 
International Journal of Geriatric Psychiatry ,17(5), 427–37.
32. Parsons, M., Anderson, C., Senior, H., et al. (2007). ASPIRE: Assessment 
of Services Promoting Independence and Recovery in Elders . University of 
Auckland, Auckland.
33. Lindesay, J., Marudkar, M., van Diepen, E., et al. (2002). The second

33. Lindesay, J., Marudkar, M., van Diepen, E., et al. (2002). The second 
Leicester survey of memory clinics in the British Isles. International 
Journal of Geriatric Psychiatry ,17, 41–7.
34. Jolley, D., Benbow, S.M., and Grizzell, M. (2006). Memory clinics. 
Postgraduate Medical Journal ,82(965), 199–206.
35. Marmot, M. (2005). Social determinants of health inequalities. Lancet ,
365(9464), 1099–104.
36. Silveira, E.R.T. and Ebrahim, S. (1998). Social determinants of 
psychiatric morbidity and well-being in immigrant elders and whites 
in east London. International Journal of Geriatric Psychiatry ,13(11), 
801–12.
37. Wang, P .S., Lane, M., Olfson, M., et al.  (2005). Twelve-month use of 
mental health services in the United States: results from the National Comorbidity Survey Replication. Archives of General Psychiatry ,
62(6), 629–40.

38. Brodaty, H., Cathy, T., Claire, T., et al.  (2005). Why caregivers of people 
with dementia and memory loss don’t use services. International 
Journal of Geriatric Psychiatry ,20(6), 537–46.
39. Allan, D. and Cloutier-Fisher, D. (2006). Health service utilization 
among older adults in British Columbia: making sense of geography. Canadian Journal on Aging ,25(2), 219–32.
40. Judd, F., Jackson, H., Komiti, A., et al. (2006). Help-seeking by rural 
residents for mental health problems: the importance of agrarian values. The Australian & New Zealand Journal of Psychiatry ,40(9), 
769–76.

9.1 General issues   1589
  9.1.1 Developmental psychopathology and 
1589
  9.1.2 Epidemiology of psychiatric disorder in childhood and adolescence  
1594
  9.1.3 Assessment in child and adolescent psychiatry  
1600
  9.1.4 Prevention of mental disorder in childhood and other public health issues  
1606
  9.2.1 Neuropsychiatric disorders  1612
  9.2.2 Speciﬁ  c developmental disorders in childhood 
and adolescence  1622
Helmut Remschmidt and Gerd Schulte-Körne
  9.2.3 Autism and the pervasive developmental disorders  
1633
1643
1654
1664

1643
1654
1664
Daniel S. Pine  9.2.7 Paediatric mood disorders  1669
1680
  9.2.9 Sleep disorders in children and adolescents  1693
1702
 9.2.11 Children’s speech and language difﬁ  culties  1710
Judy Clegg
 9.2.12 Gender identity disorder in children 
and adolescents  1718

9.3.1 The inﬂ  uence of family, school, 
1740
1747
1752
Paul Ramchandani, Alan Stein, and Lynne MurraySECTION 9
Child and Adolescent 

9.3.7 The effects of bereavement in childhood  1758
 9.5.1 Counselling and psychotherapy for children  1764
 9.5.3 Cognitive behaviour therapies for 
children and families  1777
1787
Philip A. Fisher and Elizabeth A. Stormshak 9.5.5 Medication for children and adolescents: current issues   
1793
1802
1807

1802
1807
1811

9.1
Contents
classiﬁ  cation in childhood and adolescence
  9.1.2 Epidemiology of psychiatric disorder in childhood and adolescence
  9.1.3 Assessment in child and adolescent psychiatry
  9.1.4 Prevention of mental disorder in childhood and other public health issues
9.1.1 Developmental 
psychopathology and classiﬁ  cation in childhood 
and adolescence
Classiﬁ  cation schemes of psychiatric disorders in childhood and 
adolescence have to take into account three particular features. Firstly, the individual is continually changing and growing. Sound knowledge is therefore required of the normal range of develop-ment and its limits. For example, some fears may be normal in a 5-year-old but abnormal in an 8-year-old. Once identiﬁ  ed, it is 
helpful to decide if abnormalities are due to delay in  or deviance

helpful to decide if abnormalities are due to delay in  or deviance 
from  the usual pattern of development. The implications of each 
differ, and should be classiﬁ  ed differently. Secondly, the majority of 
childhood mental health problems arise from an excess of behav-iours exhibited by many young people, such as aggression or dieting. They are seldom due to qualitatively distinct phenomena of the

childhood mental health problems arise from an excess of behav-iours exhibited by many young people, such as aggression or dieting. They are seldom due to qualitatively distinct phenomena of the 
kind more often seen in adult conditions, such as hearing voices or hanging oneself. Consequently choosing a cut-off point to make a categorical entity from a dimensional construct is more often used in child psychiatry. This is inevitably an arbitrary process (albeit informed by empirical criteria), which may lead to loss of informa-tion, and may be held to be labelling the child unnecessarily. That dimensions can be interchanged with categories does not necessar-ily mean they are unhelpful—after all, day and night are useful terms yet the boundary between them is continuous and arbitrary. Psychiatrists in particular may be criticized for ‘medicalizing’ a child’s difﬁ  culties by talking about disorders or diagnoses, whereas

other professionals and parents may prefer to see them as under-standable variations in child development, and prefer to call them ‘emotional and behavioural difﬁ  culties’ . However, diagnoses are a 
quick way to convey a lot of information that dimensions may not. 
Thus to only say a child is at an extreme of an antisocial behav iour 
dimension does not necessarily convey the association with speciﬁ  c 
reading retardation and ADHD, which could be (and often are) consequently missed.
Thirdly, children’s difﬁ  culties nearly always arise in the context 
of relationships within the family. More often than in adulthood, some or all, of the problem may appear to be the result of the functioning of the family, rather than in the individual child who may merely be reacting to the situation. For example, a child who is disobedient and shouts in class may simply be behaving the way his parents do at home. A classiﬁ  cation system will be stronger if it

can take family functioning into account—it will have a greater chance of capturing clinically important causal and therapeutic considerations.
A valid and useful classiﬁ  cation system will need to take into 
account these features and be based on a thorough understanding of normal development and how it can go wrong, rather than 
merely include static descriptions of presumed pathological states. 
The term of developmental psychopathology  was coined in the early 
1980s to denote the scientiﬁ  c study of how abnormalities can 
be understood in terms of processes underpinning human development.
(1,2) There are now journals and books incorporating 
the term into their titles.(3,4) Many disciplines are relevant, from 
embryology and genetics to social learning theory and criminology. Developmental psychopathology, besides studying the impact of pathogenic inﬂ  uences on pathways through life, such as the way the General issues

SECTION 9  child and adolescent psychiatry 1590
monoamine oxidase-A (MAOA) genotype interacts with an abu-
sive upbringing to cause conduct disorder,(5) or how speciﬁ  c read-
ing retardation leads to low self-esteem, also investigates protective mechanisms, such as the ameliorating effect of high IQ on the pro-pensity to juvenile offending, or the beneﬁ  cial effect of a trusting 
and caring relationship with an adult on the impact of childhood abuse. This chapter aims to show how ﬁ  ndings from developmen-
tal psychopathology have informed current classiﬁ  cation systems, 
and what challenges remain.
General issues
Change over time
Because mental processes and behaviour change as a child develops, it is not always clear whether the same diagnoses should be applied across the age range. Thus a highly aggressive toddler may throw himself screaming onto the ﬂ  oor in daily tantrums, whereas a

highly aggressive teenager may assault old ladies and rob them. Do they suffer from the same disorder? ICD 10 holds that they do—both meet criteria for conduct disorder, which is deﬁ  ned in terms 
of antisocial behaviour that is excessive for the individual’s age, and that violates societal norms and the rights of others. DSM IV-R on the other hand has two separate diagnoses, oppositional-deﬁ  ant 
disorder for the younger case, and conduct disorder for the older. However, as both diagnoses have similar correlates and there is a strong continuity from one to the other, the validity of the division is questionable. Y et current adult psychiatric schemes have no diag-nosis at all to apply to antisocial behaviour, unless it is part of a personality disorder.
The extent to which adult criteria should be applied to children

The extent to which adult criteria should be applied to children 
requires good empirical data. In the case of obsessive–compulsive disorder, the phenomenology is remarkably similar in childhood, so there is no problem. However, for depression the picture is rather different. Currently, ICD 10 and DSM IV-R have few emotional disorder categories speciﬁ  c to childhood, and they are 
mostly subtypes of anxiety. Mood disorders are diagnosed accord-ing to adult criteria, with the consequence that surveys of depres-sion ﬁ  nd prevalence rates close to zero under 8 years of age. Y et 
there are miserable children who cry frequently, say they are unhappy, look sad, and are withdrawn.
(6) However, they usually sleep and eat 
reasonably well, and their mood ﬂ  uctuates during the day, with 
spells when they sometimes appear more cheerful. Should they not be allowed a diagnosis? ICD 9 had a category for ‘disturbance of emotions speciﬁ  c to childhood and adolescence, with misery

spells when they sometimes appear more cheerful. Should they not be allowed a diagnosis? ICD 9 had a category for ‘disturbance of emotions speciﬁ  c to childhood and adolescence, with misery 
and unhappiness’ , and such children suffer impairment.
(7) Follow-
up studies of prepubertal children referred with this picture showed a moderately increased risk of adult type depression later on, whereas adolescents with depressive symptoms had a higher risk of adult depression.
(8) Genetic studies show that symptoms of 
depression in prepubertal children are predominantly due to environmental inﬂ  uences, whereas after puberty genetic inﬂ  uences 
become more important.
(9) Finally, tricyclics are not effective in

(9) Finally, tricyclics are not effective in 
childhood but are effective in adults. This example shows that mis-ery in younger children has some phenomenological features and external correlates in common with adult depression but also sev-eral differences, so the current approach which makes a comprehen-sive yet parsimonious classiﬁ  cation system for all ages loses validity.
In contrast, there is continuing reluctance to diagnose personal-
ity disorders in childhood. This may be because they are often seen as a life sentence of a noxious, untreatable condition, in distinction

ity disorders in childhood. This may be because they are often seen as a life sentence of a noxious, untreatable condition, in distinction 
to the general hope that there is opportunity for ‘growing out of’ conditions in childhood, or treatment for them. However, with perhaps the most destructive personality type, dissocial, there is growing evidence that the combination of antisocial behaviour and callous-unemotional traits is well established by the age of seven. Moreover, this combination of childhood characteristics has a far higher heritability than antisocial behaviour without callous-unemotional traits.
(10)
Validity
Categories need to be distinct not only in terms of the phenomena used to deﬁ  ne them, but, crucially, also in terms of external criteria. 
Even if categories can be reliably distinguished, if external criteria are the same, then one is likely to be dealing with two variants of the same condition. An analogy would be the difference between black and white cats.

Typical validating criteria in child psychiatry derived from 
developmental psychopathology are:
1Epidemiological data , such as age of onset and sex ratio. Forty 
years ago ‘childhood psychosis’ was a unitary classiﬁ  cation, but 
work showing the clear difference in age of onset helped validate the distinction between autism and schizophrenia, which seldom co-occur. Disruptive disorders occur four times more commonly in boys, whereas emotional disorders are commoner in girls.
2Long-term course . Most childhood disorders show reasonable 
homotypic continuity , that is they stay the same. Some show 
heterotypic continuity , so that for example, some cases of child-
hood hyperactivity end up as antisocial adults. This does not necessarily invalidate the category, but requires explanation.
3Genetic ﬁ  ndings . If individuals with distinct categorical diagnoses

3Genetic ﬁ  ndings . If individuals with distinct categorical diagnoses 
have relatives with different disorders, this helps validate the distinction. This has conﬁ  rmed the validity of several diagnostic 
categories, but not all. For example, it has not held for the many speciﬁ  c subtypes of anxiety disorder in ICD 10, whose validity is 
questionable. Genetic studies can also clarify the scope of symp-tom clusters. For example, family studies of autism have revealed a broader phenotype in relatives of probands,
(11) so that new dis-
orders may need to be considered, which encompass only one of the original three constituent domains of classical autism, namely social relatedness, communication problems, and repeti-tive and stereotyped behaviours.
  The hunt is now on for speciﬁ  c genes associated with particular

The hunt is now on for speciﬁ  c genes associated with particular 
psychiatric disorders. Thus dopamine receptor and transporter genes are reliably associated with Attention Deﬁ  cit Hyperactivity 
Disorder,
(12) but unless (i) the gene always leads to the disorder 
and (ii) all cases of the disorder are caused by the gene, particular genotypes are unlikely to be used to validate diagnostic categories.
4Psychosocial risk factors . The association between institutional 
upbringing with many changes of carer and reactive attachment 
disorder is so strong that it has been made a requirement for diagnosis in ICD 10. Conduct disorders are strongly associated with discords at home, whereas autistic disorders are not. However, most psychosocial risk factors are less speciﬁ  c in their associa-
tions, and so are only modestly helpful as validating criteria.
5Neuropsychological tests . The hyperkinetic syndrome is clearly 
distinguishable from conduct disorder on tests of attention such

1591
as the continuous performance task. Recently, there has been 
considerable progress in showing that one of the core deﬁ  cits 
in autism is failure on ‘theory of mind’ tests of ability, to see another person’s point of view, which non-autistic children, with comparable levels of intellectual disability, can do.
6Medical investigations . There have been many failed attempts 
in this field, including biochemical markers of adolescent depression and endocrine markers of aggression. However, the advent of functional neuroimaging is allowing exciting relatively non-invasive pictures of children’s brains to be built up, and reliable findings are beginning to emerge, for example in ADHD.
(13) In future these may well be helpful validators for 
classiﬁ  cation.
Reliability
This is a prerequisite for validity, and most categories have reason-

able inter-rater and test–retest values, once investigators are trained up. Where there are many overlapping categories, as in current deﬁ nitions of the many varieties of anxiety disorders, or personality 
disorders, inter-rater reliability falls.
(14)
Effect of informant and instrument
Traditionally information is obtained from parents and the child, and is then combined by the clinician on a case-by-case basis. However, the need for consistent diagnostic rules that is imposed by a ‘menu-driven’ approach can prove difﬁ  cult, since the weight

given to a particular informant may best vary according to condition. Thus, if a parent says a child has symptoms of conduct disorder but the child denies it, the parent is more likely to be right and the child may be covering up or ashamed. However, if the parent says the child is not depressed but the mental state examination of the child reveals otherwise, it is the parent who may be ignorant of their child’s true state. Such difﬁ  culties reduce the validity of interviews 
which use invariant combination rules. Further, in genetic studies, the heritability of a condition may vary greatly according to which informant is believed. Thus in the Virginia Twin study, conduct 
disorder was 69 per cent heritable according to the information 
derived from the mother interview, 36 per cent using information from the child, and only 27 per cent using information from the father.
(15) Studies such as these underline the need for clinically

(15) Studies such as these underline the need for clinically 
sensitive ways of combining information, and the use of multi-informant, multi-method ascertainment of information. Statistical techniques such as latent variable analysis may help reduce meas-urement error, but may build in unwarranted assumptions which distort the raw data.
Structured interviews, which accept the respondent’s reply, do 
not require lengthy training or clinically informed investigators, and so are popular in epidemiological surveys. However, the quality of information differs little from that obtained by question-naire,
(16) and often has a high false-positive and false-negative rate 
in comparison to semi-structured interviews. Direct observation, although expensive, often provides the most reliable and valid information for assessment of disruptive disorders.

There are many artefactual reasons for comorbidity appearing high, such as Berkson’s bias
(17) in clinical samples (where not all 
cases get referred, the chance of referral will be related to the combined  likelihood of referral for each condition separately), or 
overlapping criteria, or artificial subdivision of syndromes. However, even after taking these possible sources of error into account, comorbidity is marked for child psychiatric disorders. In a meta-analysis of community samples,
(18) the odds ratio for anxiety 
with either Attention Deﬁ  cit Hyperactivity Disorder (ADHD) or 
conduct disorder is 3, for anxiety and depression 8, and ADHD and conduct disorder 10. Rates are even higher in clinical samples. True comorbidity may arise through several mechanisms:
(19) (i) shared

(19) (i) shared 
risk factors (e.g. early deprivation may lead to oppositional-deﬁ  ant 
disorder and an attachment disorder), (ii) overlap between risk factors (thus a depressed mother may pass on a genetic liability to depression in her son and provide inconsistent discipline which predisposes him to conduct disorder), (iii) one disorder creating an increased risk for the other (e.g. conduct disorder leading on to drug dependency), or (iv) the comorbid pattern constitutes a meaningful syndrome (e.g. depressive conduct disorder, described below under combined categories).
Some classiﬁ  cation schemes
A simple scheme with three main groups of disorders
A simple but well researched, valid way of grouping child disorders 
‘lumps’ them into three groups, which are helpful to hold in mind when considering speciﬁ  c diagnoses:
Emotional disorders  including anxiety, depression, phobias, 
somatization, and obsessive–compulsive disorder; disruptive

somatization, and obsessive–compulsive disorder; disruptive 
disorders  including conduct disorder and hyperactivity; and devel-
opmental disorders  including intellectual disability, the autistic 
spectrum, language and reading delays, and enuresis and encopresis.
Comorbidity within each grouping is very common, but only 
occurs across groups in a minority of cases. External criteria validat-ing the differences between these groups are given in Table 9.1.1.1.9.1.1 developmental psychopathology and classification in childhood and adolescence
Table 9.1 .1.1 Validating criteria for main diagnostic groupings
Emotional 
disordersDisruptive 
disordersDevelopmental 
disorders
Age of onset over 8 under 8 under 3
Sex ratio commoner in girls 
after pubertycommoner in 
boyscommoner in 
boys
Family size normal large normalFamily history anxiety and 
depression 
increasedcriminality 
increasedrelated disorders 
may be increased

boys
Socio-economic 
statusnormal lower normal
IQ normal lower range of 
normalnormal or low, 
sometimes very 
low
Speciﬁ  c delays absent present in a third commonNeurological signs absent uncommon commonCause mixed, sometimes 
mainly geneticmixed, sometimes 
mainly 
environmentaloften mainly 
genetic

1592
Current schemes: ICD 10 and DSM IV-R
The DSM IV-R and ICD 10 committees worked closely together 
and strove to have names and criteria that are as close as possible. However, there are some general differences.
(a) ‘Picture-ﬁ  tting’ versus ‘menu-driven’ approaches
Firstly, as in adulthood, ICD 10 has one set of ‘clinical descriptions 
and diagnostic guidelines’ and a separate set of ‘diagnostic criteria for research’ . The former comprises general descriptions of disorders requiring a qualitative matching of case characteristics with the scheme, a ‘picture-ﬁ  tting’ approach which is similar to the way

clinicians practise. The latter comprises lists of symptoms with explicit criteria detailing the number and permutation required for diagnosis, a ‘menu-driven’ approach. DSM IV-R has only the latter. It has advantages in increased reliability, but is relatively cumber-some so that many clinicians do not bother to apply the criteria rigorously. Even for the simpler DSM III criteria, a study found that whilst trained researchers achieved kappa values of 0.83, 0.80, and 0.74 for attention deﬁ  cit disorder, conduct disorder, and emo-
tional disorder, the comparable ﬁ  gures for United States clinicians 
in regular practice were 0.30, 0.27, and 0.27, which are seriously 
low.
(20)
A further disadvantage of the ‘menu-driven’ approach arises in 
cases where although the clinician believes a diagnosis is present because of the severity of symptoms, their number is insufﬁ  cient to

cases where although the clinician believes a diagnosis is present because of the severity of symptoms, their number is insufﬁ  cient to 
meet criteria. For example, consider the following youth: he repeat-edly mugs old ladies, sets ﬁ  res frequently, often argues, is often 
spiteful or vindictive, has unusually severe tantrums, and has no friends or job because of his behaviour. According to ICD 10 research diagnostic criteria (or DSM IV-R criteria) he has no diag-nosis, as he has two but not three symptoms of conduct disorder, and three but not four symptoms of oppositional-deﬁ  ant disorder. 
However, according to ICD 10 ‘diagnostic guidelines’ he easily meets the requirements for conduct disorder since ‘any category, if marked, is sufﬁ  cient’ .
(b) Multiple diagnoses
A second difference between ICD 10 and DSM IV-R is in multiple 
diagnoses. ICD 10 encourages the selection of one diagnosis that closest ﬁ  ts the picture, assuming that differences are due to a varia-

tion upon the typical theme. DSM IV-R (and the closely linked ICD 10 research criteria) encourage selection of as many diagnoses as criteria are met. Problems arise with this approach when symp-toms are common to two disorders, for example irritability con-tributes to affective disorders and to conduct disorders, so double coding is more likely. Since comorbidity is very common in clinical practice, multiple coding is frequent using a ‘menu-driven’ approach so that it begins to approach a dimensional system and to lose the advantages of categorization.
The pros and cons of each approach will vary according to 
whether extra information is conveyed by the second diagnosis. 
Where there is good evidence of the validity of common comorbid

Where there is good evidence of the validity of common comorbid 
conditions, ICD 10 has combined categories. Thus the external validating characteristics of ‘depressive conduct disorder’ are simi-lar to those of pure conduct disorder, with no increase of affective disorders in individuals, nor in their relatives, followed up to adult-hood. Double coding would convey erroneous information about the depressive aspect. ‘Hyperkinetic conduct disorder’ , on the other hand, is characterized by more severe neuropsychological deﬁ  cits 
than occur in either condition alone, and by worse psychosocial outcome in adulthood. Double coding would not convey the poor 
prognosis.
(c) Multiaxial framework
The ICD 10 has a multiaxial framework for psychiatric disorders in 
childhood and adolescence(21) which will be described here. DSM

childhood and adolescence(21) which will be described here. DSM 
IV-R uses a somewhat different multiaxial framework, which is applicable for disorders arising at all ages. It will not be described here except as a contrast to ICD 10. Each axis except the last (psy-chosocial impairment) is coded independently of the apparent causal contribution to the psychiatric syndrome. This avoids tricky decisions about causality and allows conditions to be recognized and clinical needs addressed.
(i) Axis one: clinical psychiatric syndromes
Criteria for particular diagnoses are described in the relevant chap-ters of this text.
(ii) Axis two: speciﬁ  c disorders of development

These include speech and language, reading, spelling, and motor development. In DSM IV-R they are included in Axis one. However, having a separate axis helps to ensure that they are not overlooked. This can easily happen, for example, in children with conduct dis-order, where the antisocial behaviour tends to command attention, while in fact one-third of the children also have speciﬁ  c reading 
retardation (dyslexia), which if untreated worsens the progno-sis.
(22) It very desirable to administer standardized psychometric 
tests in order to characterize speciﬁ  c disorders of development.
(iii) Axis three: intellectual level
The categories are no intellectual disability (IQ 70 or over), mild

The categories are no intellectual disability (IQ 70 or over), mild 
intellectual disability (50–69), moderate intellectual disability (IQ 35–49), severe intellectual disability (IQ 20–34), and profound intellectual disability (IQ under 20). In DSM IV-R personality dis-orders are also included on the axis.
Subtyping intellectual disability gives a good example of sub-
stantial differences which arise when categories are imposed on top of a dimensional construct. If all children with an IQ below 50 are taken together (often together also called severe), and compared with those having an IQ of 50–70 (mild), major differences emerge on independent validating criteria, as shown in Table 9.1.1.2.
From the table it will be seen that there are major differences

From the table it will be seen that there are major differences 
between the categories on fronts as varied as brain pathology and life expectancy. There is no particular psychiatric pattern arising in children with intellectual disability, rather the incidence of all dis-
orders is raised, so that in those with IQ under 50, fully one half 
have a psychiatric disorder.
(23)
(iv) Axis four: associated medical conditions
All medical conditions should be coded. A few have speciﬁ  c asso-
ciations with psychiatric disorders, for example tuberous sclerosis predisposes to autism, Cornelia de Lange syndrome to self-injury; Down syndrome on the other hand protects against autism but often leads to presenile dementia. Even where there is no speciﬁ  c 
disorder, congenital syndromes are often characterized by a partic-ular pattern of behaviour. The study of these behavioural pheno-
types  is a discipline in its own right.
(v) Axis ﬁ  ve: associated abnormal psychosocial conditions

These include a range of pyschosocial hazards, from abnormal 
intrafamilial relationships such as physical or sexual abuse, to men-tal disorders in other family members, distorted intrafamilial com-munication patterns, abnormal upbringing, e.g. in an institution, SECTION 9  child and adolescent psychiatry

1593
acute life events, and chronic interpersonal stress arising from dif-
ﬁ culties at school. Each is coded dimensionally on a three point 
scale. As the number of psychosocial adversities goes up, the rate of psychiatric disorders increases.
(24) Conduct disorder is particularly 
associated with poor immediate psychosocial environments. As with other axes, abnormalities are coded irrespective of apparent cause. This is particularly relevant since while perhaps 20 years ago the mechanism was thought to be directly environmental, in the last 10 years good evidence has been collected to show that some environmental characteristics of the home are genetically mediated.
(25)
For example, the association between lack of books in the home and poor child reading is partly mediated through parents with lower IQ buying fewer books.
(vi) Axis six: global social functioning

Here a judgement is made on a nine point dimensional scale ranging from superior social functioning to profound and perva-sive social disability. Unlike other axes, ratings of disability are not independent, but have to be judged as due to a psychiatric or devel-opmental disorder on axes one to three. Thus impairment arising from adverse circumstances cannot be coded—it must arise from intraindividual factors. This rule therefore excludes recognition of psychosocial interventions which aid functioning, from reduction of parental Expressed Emotion to changing schools. DSM IV-R studies often use the Children’s Global Assessment scale,
(26) an

(26) an 
adaptation of the Global Assessment of Functioning (GAF) used in adults. An advantage of the CGAS is that it is rated without  impairment having to be caused by psychiatric disorder. A disad-
vantage is that psychiatric symptoms, rather than impairment alone, contribute to the rating.
(d)  Should impairment of social function be part of 
psychiatric diagnosis?
In general, ICD 10 and DSM IV-R do not require impairment of 
social functioning to be present in order to make a diagnosis. There 
are exceptions, thus in DSM IV-R, oppositional-deﬁ  ant disorder 
does require impairment. With many qualitatively distinct adult

does require impairment. With many qualitatively distinct adult 
disorders, having no impairment criterion makes sense, so that a person experiencing the delusions and hallucinations characteris-tic of schizophrenia, but able to go to work and form relationships while on neuroleptics still has schizophrenia. But should a child who says he is afraid of dogs and crosses to the other side of the pavement on seeing one, but otherwise functions well, be deemed to suffer from a phobia? If impairment criteria are not applied, very high rates of disorder are obtained in epidemiological surveys. This lacks credibility with the general public, who may then dismiss all psychiatric problems in children, and is unrealistic for clinicians and health planners, who would not see most of the identiﬁ  ed 
individuals as cases needing treatment. For example, a large epide-miological survey

(27) found that using DSM III criteria, 50 per cent 
of children and adolescents had a diagnosis. However, when an impairment criterion was added, the ﬁ  gure came down to 18 per cent. 
This would appear to be a much more realistic ﬁ  gure. However, it 
could be argued that social impairment is too constraining, and for example would exclude an adolescent who is fairly depressed but able to function. The term impact  can be used to include subjective 
distress as well as impairment, and is gaining in popularity among many child psychiatrists.
(28)
Falling through the cracks: children with 
social impairment but no diagnosis
Diagnostic systems have to be practically useful above all. If they

(28)
Diagnostic systems have to be practically useful above all. If they 
are overinclusive, the risk is that there are too many categories, which have poor reliability and high overlap. If on the other hand they are too exclusive, the risk is that there will be many individuals suffering from problems which are not encompassed by the scheme. In one thorough survey, 9.4 per cent had no diagnosis but signiﬁ  -
cant impairment.
(29) Across a variety of ‘caseness’ measures, the 
individuals were as disturbed as those with a diagnosis. Many of the difﬁ  culties were around relationships with parents and siblings, 
and arguably, such children who have symptoms associated with psychosocial impairment should be regarded as suffering from a psychiatric disorder.
Classiﬁ  cation of child psychiatric conditions has advanced enor-

mously in the last 20 years. There is a much stronger empirical basis to support current schemes, which are grounded in the many scientiﬁ  c disciplines that contribute to developmental psychopa-
thology. Nonetheless there are considerable obstacles to overcome if DSM V and ICD 11 are to be major steps forward.
T o access the journal Development and Psychopathology , visit http://journals.
cambridge.org/action/displayJournal?jid=DPP9.1.1 developmental psychopathology and classification in childhood and adolescence
Table 9.1.1.2  Characteristics of children with severe versus mild 
intellectual disability
Severe retardation Mild retardation
Deﬁ  nition IQ under 50 IQ 50–70
Social 
functioningInvariably marked 
impairmentMany have minor or no 
Cause Organic pathology in 
majorityUsually no organic cause 
evident
Family history Parents and siblings usually

Social 
evident
Family history Parents and siblings usually 
of normal intelligenceParents and siblings often at 
lower levels of intelligence
Background Fairly equal distribution 
across SES levelsMuch commoner at lower 
SES levels
Neglect at home unlikely Neglect at home more likely
Appearance Dysmorphic features 
often evidentNormal appearance
Medical 
complicationsPhysical handicap common 
(e.g. cerebral palsy)Physical handicap uncommon
Major health problems 
frequentHealth in normal range
Life expectancy shortened Life expectancy normal
Fertility low Fertility little impaired
complicationsSevere and pervasive 
disorders such as hyperactivity, autism, 
and self-injury especially 
commonDisorders similar in type 
to those found in children without MR, but occur more 
frequently
Presentation of disorders 
often altered, mental

often altered, mental 
state may be difﬁ  cult to 
determineForm of disorders and mental 
state examination similar to 
children without retardation

1594 SECTION 9  child and adolescent psychiatry
Cicchetti, D. and Cohen, D. (eds.) (2003). Developmental psychopathology
(2nd edn). Wiley, New Y ork.
Taylor, E. and Rutter, M. (2008). Classiﬁ  cation. In Rutter’s child and 
adolescent psychiatry  (5th edn) (eds. M. Rutter, D. Bishop, D. Pine, 
et al.). Blackwell, Oxford.
Goodman, R. and Scott, S. (2005). Child psychiatry  (2nd edn). Blackwell, 
Oxford.
T o access the ofﬁ  cial website discussing issues around DSM IV criteria, visit 
http://www.dsmivtr.org/index.cfm and regarding ICD 10 visit http://www.who.int/classiﬁ  cations/icd/en/
 1. Cicchetti, D. (1984). The emergence of developmental 
psychopathology. Child Development ,55, 1–7.
 2. Rutter, M. (1988). Epidemiological approaches to developmental 
psychopathology. Archives of General Psychiatry ,45, 486–95.
 3. T o access the journal Development and Psychopathology , visit http://
journals.cambridge.org/action/displayJournal?jid=DPP

 4. Cicchetti, D. and Cohen, D. (eds.) (2003). Developmental 
psychopathology  (2nd edn). Wiley, New Y ork.
 5. Kim-Cohen, J., Caspi, A., Taylor, A., et al. (2006) . MAOA, maltreatment, 
and gene-environment interaction predicting children’s mental health: new evidence and a meta-analysis. Molecular Psychiatry, 11, 903–13 .
 6. Puura, K., Tamminen, T., Almqvist, F., et al. (1997). Should depression 
in young children be diagnosed with different criteria? European Child 
& Adolescent Psychiatry ,6, 12–19.
 7. Costello, E.J., Mustillo, S., Erkanli, A., et al. (2003). Prevalence and 
development of psychiatric disorders in childhood and adolescence. Archives of General Psychiatry ,60, 837–44.
 8. Harrington, R., Fudge, H., Rutter, M., et al. (1990). Adult outcomes of

 8. Harrington, R., Fudge, H., Rutter, M., et al. (1990). Adult outcomes of 
childhood and adolescent depression––I. Psychiatric status. Archives of 
General Psychiatry ,47, 465–73.
 9. Scourﬁ  eld, J., Rice, F., Thapar, A., et al. (2003). Depressive symptoms 
in children and adolescents: changing aetiological inﬂ  uences with 
development. Journal of Child Psychology and Psychiatry, and Allied 
Disciplines ,44, 968–76.
10. Viding, E., Blair, R.J.R., Mofﬁ  tt, T.E., et al. (2005).  Evidence for 
substantial genetic risk for psychopathy in 7-year-olds. Journal of Child 
Psychology and Psychiatry, and Allied Disciplines, 46, 592–7 .
11. Rutter, M. (2000). Genetic studies of autism: from the 1970s into the 
millennium. Journal of Abnormal Child Psychology ,28, 3–14.
12. Thapar, A., O’Donovan, M., and Owen, M.J. (2005). The genetics of

12. Thapar, A., O’Donovan, M., and Owen, M.J. (2005). The genetics of 
14, R275–82.
13. Rubia, K., Smith, A.B., Brammer, M.J., et al. (2005). Abnormal brain 
activation during inhibition and error detection in medication-naive adolescents with ADHD. The American Journal of Psychiatry ,162, 1067–75.
14. Thomsen, P ., Jorgensen, J., and Nedergaard, N. (1992). ICD-10: a ﬁ
 eld 
study in a Danish child psychiatric unit. European Psychiatry ,7, 287–91.
15. Eaves, L., Silberg, J., Meyer, J., et al. (1997). Genetics and developmental 
psychopathology: 2. The main effects of genes and environment on behavioral problems in the Virginia twin study of adolescent behavioral development. Journal of Child Psychology and Psychiatry, and Allied 
Disciplines ,38, 965–80.
16. Boyle, M., Offord, D., Racine, Y., et al. (1997). Adequacy of interviews

16. Boyle, M., Offord, D., Racine, Y., et al. (1997). Adequacy of interviews 
vs checklists for classifying childhood psychiatric disorder based on parent reports. Archives of General Psychiatry ,54, 793–9.
17. Berkson, J. (1946). Limitations of the application of fourfold table 
analysis to hospital data. Biometrics ,2, 47–53.
18. Angold, A., Costello, E., and Erkanli, A. (1999). Comorbidity. Journal of 
Child Psychology and Psychiatry, and Allied Disciplines ,40, 57–87.
19. Rutter, M. (1997). Comorbidity: concepts, claims and choices. Criminal 
Behaviour and Mental Health ,7, 265–85.
20. Prendergast, M., Taylor, E., Rapoport, J., et al. (1988). The diagnosis of 
childhood hyperactivity: a US-UK cross-national study of DSM-III and ICD-9. Journal of Child Psychology and Psychiatry, and 
Allied Disciplines ,29, 289–300.
21. World Health Organization. (1996). Multiaxial classiﬁ  cation of child 
and adolescent psychiatric disorders . Cambridge University Press,

and adolescent psychiatric disorders . Cambridge University Press, 
22. Trzesniewski, K., Mofﬁ  tt, T., Caspi, A., et al. (2006). Revisiting the 
association between reading achievement and antisocial behaviour: new evidence of an environmental explanation from a twin study. Child Development, 77, 72–88 .
23. Stromme, P . and Diseth, T. (2000). Prevalence of psychiatric diagnoses 
in children with intellectual disability: data from a population-based study. Developmental Medicine and Child Neurology ,42, 266–70.
24. Appleyard, K., Egeland, B., van Dulmen, M., et al. (2005). When more 
is not better: the role of cumulative risk in child behavior outcomes. Journal of Child Psychology and Psychiatry, and Allied Disciplines ,
46, 235–45.
25. Braungart, J., Fulker, D., and Plomin, R. (1992). Genetic inﬂ  uence of

25. Braungart, J., Fulker, D., and Plomin, R. (1992). Genetic inﬂ  uence of 
the home environment during infancy: a sibling adoption study of the HOME. Developmental Psychology ,28, 1048–55.
26. Shaffer, D., Gould, M., Brasic, J., et al. (1983). A children’s global 
assessment scale (CGAS). Archives of General Psychiatry ,40, 1228–31.
27. Bird, H., Y ager, T., Staghezza, B., et al. (1990). Impairment in the 
epidemiological measurement of childhood psychopathology in the 
community. Journal of the American Academy of Child and Adolescent 
Psychiatry ,29, 796–803.
28. Goodman, R. and Scott, S. (2005). Child psychiatry  (2nd edn). 
29. Angold, A., Costello, E., Farmer, E., et al. (1999). Impaired but 
undiagnosed. Journal of the American Academy of Child and Adolescent 
Psychiatry ,3, 129–37.
9.1.2 Epidemiology of 
psychiatric disorder in childhood and adolescence

Epidemiology is the study of patterns of disease in human popula-
tions.(1) Patterns are non-random distributions, and patterns of 
disease distribution occur in both time and space. Whenever we 
observe a non-random distribution, we have the opportunity to 
identify causal factors that inﬂ  uence who gets a disease and who 
does not. For example, we observe that depression rises rapidly after puberty in girls, but not to the same extent in boys.
(2) This 
non-random distribution in time suggests that there may be some-thing about puberty in girls that is causally related to depression.
(3)
An example of disease distribution in space can be seen in the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) study of ﬁ  ve sites in the United States and 
Puerto Rico.
(4) Although the prevalence of psychiatric disorders

(4) Although the prevalence of psychiatric disorders 
was fairly similar across sites, the likelihood that a psychiatric diag-nosis was accompanied by signiﬁ  cant functional impairment was 
much higher in children at the mainland sites than in Puerto Rico. This offers the opportunity to study between-site differences that might result in differences in the level of impairment caused by 
psychiatric disorders. The task of epidemiology is to understand these observed patterns in time and space, and to use this under-
standing as a basis for the prevention and control of disease.

1595
Epidemiological medicine has both similarities to and differences 
from clinical medicine. Like clinical medicine, epidemiology is an action-oriented discipline, whose goal is intervention to prevent and control disease. Scientiﬁ  c knowledge about the cause and 
course of disease is another common goal. Epidemiology also reflects clinical medicine in using two methods of attack on 
disease: tactical  methods, concerned with the practical and admin-
istrative problems of disease control at the day-to-day level, and strategic  methods, concerned with ﬁ  nding out what causes disease 
so that new weapons of prevention and control can be engi-neered.
(5,6) Thus, for example, in their tactical or public health role

(5,6) Thus, for example, in their tactical or public health role 
epidemiologists can be found reporting on the prevalence of adolescent drug abuse, the social burden (including cost) that drug abuse creates, and the best ways to control its spread, while others working at the strategic level might be exploring the science under-lying environmental constraints on gene expression.
Epidemiology diverges from clinical medicine to the extent that 
it concentrates on understanding and controlling disease processes in the context of the population at risk , whereas the primary focus 
of clinical medicine is the individual  patient. This does not mean

of clinical medicine is the individual  patient. This does not mean 
that epidemiology is not concerned with the individual; on the contrary, it is very much concerned with understanding the indi-vidual’s illness and the causes of that illness. The difference lies in the frame of reference. Put crudely, clinical medicine asks: ‘What is wrong with this person and how should I treat him or her ?’ 
Epidemiology asks: ‘What is wrong with this person and what is it 
about him or her that has resulted in this illness ?’ Why is this child 
depressed, but not her brother? If her mother is also depressed, is the child’s depression a cause, a consequence, or an unrelated, chance co-occurrence? Such questions immediately set the individ-ual child within a frame of reference of other children, or other fam-ily members, or other people of the same sex or race or social class.
Sampling, or selecting the population within which to count

Sampling, or selecting the population within which to count 
cases, is of central importance in epidemiology. Counting cases is an important ﬁ  rst step towards measuring the social burden caused 
by a disease, and the effectiveness of prevention. For most diseases, 
however, simply counting the number of individuals presenting 
for treatment will produce estimates that are seriously biased by referral practices, ability to pay, and other factors. This is a big problem in child psychiatry because parents, teachers, and pedia-
tricians all serve as ‘gatekeepers’ to treatment.
(7) Community-based

(7) Community-based 
data are needed to measure the extent of need, and the unmet need, for prevention or treatment. Methods for assessing psychiatric dis-orders in the general population are discussed in another chapter. However, it is worth noting that methods for assessing disorder, whether they take the form of interviews, questionnaires, or neuro-psychiatric tests, can only be as good as the taxonomy they are designed to operationalize. Current instruments mainly use scor-ing algorithms that turn the responses into diagnoses based on the DSM-IV or ICD-10 taxonomies. If these taxonomies do not mirror the ‘reality’ of psychiatric disorder then the results of using inter-views or questionnaires based on them will in turn be faulty.
Estimating the burden of child and 
adolescent psychiatric disorders
In a world of scarce health care resources, it is important to under-

stand the size of the burden to the community caused by these disorders. Burden, in terms of numbers affected, impact on the individual, and cost to the community, is a crucial factor in the 
battle for resources for treatment and prevention.
Attempts to reduce the burden of mental illness must, of neces-
sity, pay attention to the early years. It is becoming increasingly clear that most psychiatric disorders have their onset before adult-hood, and that many should be regarded as chronic or relapsing disorders. For example, the National Comorbidity Survey Replication, a representative population sample of over 9000 adults aged 18 and over in the United States,
(8) found that, of the 
46.4 per cent of all participants reporting one or more psychiatric disorders during there lifetime, half reported onset by age 12, and three-quarters by age 24.

(9) Since we can expect a lot of forgetting 
of early episodes by older participants,(10) it is likely that onset in 
childhood is even more common than this.
If the burden of mental illness begins to be felt in childhood, it is

If the burden of mental illness begins to be felt in childhood, it is 
important to know the extent of the problem so that we can begin to plan for treatment and prevention. Unfortunately, the data on which to build such estimates are very sparse. We have to rely on a national prevalence study of psychiatric disorders in the United Kingdom, and another of a large area of Brazil, together with a few national or large community surveys using symptoms scales, and a handful of diagnosis-based studies in smaller community samples, some of them longitudinal. Questionnaire-based surveys are not very useful for measuring prevalence, because they tend to deﬁ  ne 
‘caseness’ in terms of a certain percentage of the sample with high scores; a method that predeﬁ  nes prevalence.
In the past decade the United Kingdom has carried out a national 
prevalence study,

(11,12)  conducted by the Office for National 
Statistics, with funding from the Department of Education and other agencies. The primary purpose was to produce prevalence estimates of conduct, emotional, and hyperkinetic disorders, as well as pervasive developmental disorder, eating disorders, and tic disorders, using both ICD-10 and DSM-IV criteria. The second aim was ‘to determine the impact  or burden  of children’s mental 
health. Impact  covers the consequences for the child; burden  reﬂ ects 
the consequences for others’ .
(13) (p. 185). Third, the study measured 
service use. A stratified random sampling plan for England, 
Scotland, and Wales produced a sample of 10 438 children aged 5 to 15. Parent and child were interviewed using the Development and Well-Being Assessment (DAWBA),

(14) a computer-assisted lay 
interview that uses a ‘best-estimate’ approach to diagnosis, in which 
responses recorded by lay interviewers are evaluated by clinicians. The ﬁ  rst interview wave, conducted in 1999,
(13) was followed by a 
questionnaire mailed 18 months later to all ‘cases’ with a diagnosis at Time 1, and a one-in-three random sample of non-cases. A second interview of all those completing questionnaires at Time 2, and all others who were cases at Time 1, was completed in 2002.
(15)
By weighting the responses to account for the various selection factors and for non-response, Meltzer and colleagues developed estimates of prevalence (i.e. the presence of a disorder at the Time 1 interview), of incidence (new cases between the two interviews), and of persistence.

The UK study found that almost one child in 10 (9.5 per cent) 
aged 5 to 15 had a psychiatric disorder based on the ICD-10 classiﬁ  -
cation system. Prevalence was higher in adolescents (11.2 per cent at 11 to 15) than in children (8.2 per cent at 5 to 15), and in boys (11.4 per cent than girls 7.6 per cent). Conduct disorders were the most common (5.3 per cent), followed by anxiety disorders (3.8 per cent). Depression was rare in both sexes and all age groups 9.1.2 epidemiology of psychiatric disorder in childhood and adolescence

1596
(0.9 per cent over all), as were hyperkinetic disorders (1.4 per cent). 
Seven per cent of previously unaffected children developed a psychiatric disorder in the 3 years between the interviews. Four per cent developed a new emotional disorder (anxiety and/or depres-sion), and 5 per cent a behavioural and/or hyperkinetic disorder. More girls developed emotional disorders, and more boys developed behavioural disorders. Persistence, measured as the presence of the same diagnosis the years apart, was higher for behavioural disorders (43 per cent) than for emotional disorders (about one in four).
Factors affecting prevalence estimates

It is not a simple matter to compare the British prevalence rates with those from other countries, because there are few large stud-ies, and the age ranges do not overlap. A study of youth age 7 to 14 in south-eastern Brazil, which used the same diagnostic interview but the DSM-IV taxonomy, found an overall prevalence of 12.7 per cent. Although prevalence estimates were slightly different from those reported by the UK study, the relative ordering was the same. Behavioural disorders were again the most common (7 per cent), followed by anxiety disorders (5.2 per cent) and ADHD (1.8 per cent). Once again, depression was rare (1.0 per cent). Other studies from around the world
(16) usually generate prevalence rates of

(16) usually generate prevalence rates of 
around 20 per cent. This puts the British and Brazilian studies at the low end of the range. However, there are many factors other than the ‘true’ rate of psychiatric disorder (if there is any such thing) that affect a published prevalence rate. The most important of these are:
1The time frame of the diagnostic measure . Questions can be 
asked about symptoms occurring ‘now’ , ‘in the past month’ , ‘in the past 3, 6, or 12 months’ , or ‘ever’ . Clearly, if recall is accurate the latter questions will elicit more symptoms than the former. Unfortunately, recall is not always accurate. Prevalence rates are 
higher from interviews with longer time frames, but not as much

higher from interviews with longer time frames, but not as much 
higher as would be consistent with accurate recall. For example, The National Comorbidity Study Replication, based on a nation-ally representative sample of adults in the United States, found that the lifetime prevalence of any disorder was 46.4 per cent, while the 12-month prevalence was 26.2 per cent. This means that 26.2 per cent /46.4 per cent = 56.5 per cent of all cases across the lifespan were present in the past 12 months. This could be explained in several ways: (i) there was an epidemic of psychiat-ric disorders in the 12 months before the survey; (ii) over half of all psychiatric diseases are chronic; once they occur they remain active for the rest of life; (iii) many early episodes are forgotten, and people report the onset of the most recent episode as the ﬁ  rst occurrence of the disorder. In the absence of any

evidence for (i), some combination of (ii) and (iii) seems the most likely explanation. We have evidence that the reliability with which children and adults recall the ﬁ  rst occurrence of 
a symptom falls 
dramatically after 3 months,(17) and recommend 
concentrating on symptoms occurring in the past 3 months if a fairly reliable estimate is sought.
  In general, when comparing prevalence rates from different 
reports it is important to bear in mind the time frame. In a com-parison of reported rates of child and adolescent depression 
published since the 1970s, we found that the time frame of the interview accounted for most of the variance, compared with taxonomy (DSM-III, DSM-IIIR, DSM-IV , ICD-9, ICD-10), diag-
nostic interview, or birth cohort.
(2)
2The number and nature of the informants . For several decades now

(2)
2The number and nature of the informants . For several decades now 
clinicians and epidemiologists alike have recommended collect-ing information about a child from a range of informants: the parents, siblings, teachers, and peers, as well as the child. Most diagnostic instruments, whether questionnaires or interviews, exist in forms for diverse informants, with scoring algorithms that allow a diagnosis to be made on the basis of one informant or more. In the latter case, most follow the rule that clinicians gener-ally observe, of counting a symptom as present if reported by any informant, rather than expecting agreement among informants, which rarely occurs.
(18) Rates of psychiatric disorder will vary 
with the number of informants, and also depending on which informants report on which diagnoses. For example, across 
repeated assessments of 1420 children and adolescents, only 26 per cent of those with a diagnosis from the child interview also

repeated assessments of 1420 children and adolescents, only 26 per cent of those with a diagnosis from the child interview also 
had one from the parent interview, and only 22 per cent of those with a diagnosis based on the parent interview had one from the 
child interview. This was statistically a highly signiﬁ  cant level 
of agreement (OR 5.4, 95 per cent; CI 3.6, 7.9; p <.0001), but 
nevertheless only 13.5 per cent of cases were reported by both informants. Readers of epidemiological studies need to decide for 
themselves how much the number and type of informant matters in judging the accuracy of a prevalence estimate of a speciﬁ  c dis-
order. For example, parents often do not know much about their children’s drug use, while young children themselves generally have little insight into their own hyperactivity, and teachers seldom notice children’s depression. Prevalence rates based solely 
on these informants would be likely to be quite low.

3The age and sex of the subjects . The prevalence rates of different 
disorders vary markedly by age, sex, and age-by-sex across child-hood and adolescence. For example, a meta-analysis of 26 stud-
ies of child and adolescent depression
(2) estimated the prevalence 
of adolescent depression (5.6 per cent) as twice that of childhood 
depression (2.9 per cent), and that of adolescent girls (5.9 per cent) as signiﬁ  cantly higher than that of adolescent boys (4.6 per 
cent). Figure 9.1.2.1 shows prevalence rates of any psychiatric disorder (dotted lines) from a representative population sample 
of 1420 youth assessed regularly between ages 9 and 21. It is clear that prevalence, even when measured over time in the same sub-jects, varies markedly with age. This is because some of the com-mon disorders of childhood, such as functional enuresis and

encopresis, ADHD, and separation anxiety, diminish as children grow up, but then later on the problems of adolescence and 
young adulthood, such as drug abuse and depression, take their 
place. Between about 11 and 14, when the disorders of childhood 
have faded and those of adulthood not yet appeared, relatively few children have disorders. Prevalence rates will also differ 
depending on the distribution of males and females in the 
sample. Boys are signiﬁ  cantly more likely to have developmental 
disorders, enuresis and encopresis, and ADHD in the early years, 
and drug abuse in the later years. Although girls are more vulner-
able to depression after puberty,
(19) this does not have a large 
effect on the overall prevalence of psychiatric disorder.
4The inclusion of measures of functional impairment . Most DSM-
IV and ICD-10 diagnoses require that to be clinically signiﬁ  cant, 
symptoms must have a harmful effect on patients’ ability to SECTION 9  child and adolescent psychiatry

1597
function in their normal environments.(20) There is a wide range 
of measures of functional impairment,(20) and many diagnostic 
interviews employ measures of impairment as part of their diag-nostic algorithms.
 The inclusion or exclusion of a measure of impairment can 
make a dramatic difference to prevalence estimates. For example, version 2.3 of the Diagnostic Schedule for Children, a widely used interview for youth and parents, uses two measures of impairment. First, if a symptom is reported further questions are asked about whether it affects the child’s functioning. Second, the interviewer scores the child on the Global Assessment Scale,
(21) which rates the child’s overall level of function from 0 to 
100. Table 9.1.2.1 shows the impact on the prevalence of any anxiety disorder of including or excluding either or both of these measures of impairment, using data from a multi-site epidemio-logical study.
(21) When no measure of impairment was used

(21) When no measure of impairment was used 
almost 40 per cent of subjects received an anxiety diagnosis. With both criteria applied at their most rigourous level, the prevalence of anxiety was cut to 3.2 per cent.Future directions in the epidemiology of 
child and adolescent psychiatric disorders
Up to this point, the role of epidemiology has been mainly a 
descriptive one, addressing the basic questions: how many? who? 
where? when? However, child psychiatry is changing, and epidemi-ology will change as well. The goal is now to understand how risk exposure and vulnerability change over the life course, and how the requirements of ‘normal’ development shape the types of psychopathology that emerge if these requirements are not met. The term ‘developmental epidemiology’ , ﬁ  rst coined by Kellam 
in the 1970s,
(22) is useful to describe what epidemiology is doing 
these days.
In this section we describe some rapidly growing research areas

In this section we describe some rapidly growing research areas 
that will contribute to the next generation of studies, and will con-tribute to the shift from ‘child psychiatric epidemiology’ to ‘develop-mental epidemiology’ . We discuss the future under ﬁ  ve headings: 
longitudinal research, genetic epidemiology, life course epidemiology, intergenerational epidemiology, and prevention science.
Longitudinal research
Although there have been many longitudinal develo pmental studies, 
some of them beginning at birth (or even before), longitudinal studies of psychiatric disorders had to await the development of appropriate technology; speciﬁ  cally, data collection methods that 
validly and reliably translated the psychiatric taxonomy into instru-ments that could be used repeatedly with the same subjects. Several of these have become available in the past 20 years.
(23)

(23)
There are now several research groups that have used their longi-
tudinal data to look at continuities and discontinuities in mental illness from childhood into adolescence and beyond. Some of the longitudinal studies have followed their subjects into adulthood.
(16)
These are beginning to show indications of continuity of disorder across childhood and adolescence,
(24) and between temperamental 
characteristics in early childhood and the onset of psychiatric disor-ders in late adolescence and young adulthood.
(25)
Genetic epidemiology
There have been two revolutions in genetic epidemiology in the past two decades that will have a tremendous impact on psychiatry in the next decade.
(a) Psychiatric–behavioural genetics
The ﬁ  rst revolution occurred when the methods of psychiatric epide-

miology were applied to behavioural genetics. Psychiatric interviews 9.1.2 epidemiology of psychiatric disorder in childhood and adolescence
Fig. 9.1.2.1 (solid lines) shows the effect of applying a functioning criterion 
to diagnoses. It has the effect of ﬂ  attening the U-shaped curve and revealing a doubling of psychiatric disorder with age, from around 5 per cent at age 9–10 to 10 per cent at age 21. This gradual increase is seen in both boys and girls.051015202530354045
10 12 14 16 19 21Male SED Female SED
Male any Dx Female any Dx
Table 9.1.2.1 Effect of different rules for deﬁ  ning impairment on the per cent prevalence of any anxiety disorder (parent or child interview ) 
using the DISC 2.3
Diagnosis without diagnosis-speciﬁ  c impairment criteria Diagnosis with diagnosis-speciﬁ  c impairment criteria
Criteria only CGAS < = 70 
(mild)CGAS < = 60 
(moderate)CGAS < = 50

(moderate)CGAS < = 50 
(severe)Criteria only CGAS < = 70 
(severe)
Any anxiety diagnosis 39.5 18.5 9.6 4.3 20.5 13.0 7.2 3.2
(Reproduced from D. Shaffer  et al. The NIMH diagnostic interview schedule for children version 2.3 (DISC 2.3): description, acceptability, prevalence rates, and  performance in the 
MECA study, Journal of the American Academy of Child and Adolescent Psychiatry , 35, 865–77, copyright 1996, American Acadamy of Child and Adolescent Psychiatry, Lippincott 
Willams & Wilkins.)
DISC = Diagnostic Interview Schedule for Children. CGAS = Children’s Global Assessment Scale.

SECTION 9  child and adolescent psychiatry 1598
like those described earlier were used in studies with genetically 
informative designs, such as twin, adoption, family, and migrant studies. For the ﬁ  rst time, researchers examined cate-
gorical disorders such as depression, in ways that approximate clinical diagnosis. Furthermore, behavioural geneticists began to take seriously, issues of sampling, so that they could talk about the contribution of genes to disease in the population as a whole, rather than in highly selected families or groups. There have also been some longitudinal studies looking at how genes can have different effects at different developmental stages.
(26)
(b) Molecular genetics

(26)
The second genetic revolution occurred when it became feasible to apply the methods of molecular genetics to epidemiologic samples. This development opens up the opportunity to use not only twin or adoption studies but a wide range of singleton samples to test theories about candidate genes for speciﬁ  c symptoms. Even more 
exciting is the new opportunity to use the treasure house of data from longitudinal studies to test for gene–environment interactions. Such studies can answer questions about which genes interact with which environmental factors, and at what develop-mental stage.
(27,28)
Life course epidemiology

(27,28)
Life course epidemiology is the study of long-term effects on chronic disease risk, of physical and social exposures, during gesta-tion, childhood, adolescence, young adulthood, and later adult life. It includes studies of the biological, behavioural, and psychosocial pathways that operate across an individual’s life course, as well as across generations, to influence the development of chronic diseases.
(29)
Life course epidemiology has developed a special concern with 
‘the “embodiment” of social phenomena into the biological’(30)
encapsulated in the concept of ‘health inequalities’ . This concern arose historically from work showing that mortality from many diseases is spread unequally across the population and that these differences in risk can be linked to social inequalities that often go back to infancy or even to the parental generation. This body of work has had enormous signiﬁ  cance for international thinking

about social policy and is having a direct effect on the allocation of public resources in the United Kingdom and elsewhere.
Intergenerational epidemiology
A life course approach to epidemiology intertwines biological and social transmission of risk across generations, recognizing that geographical and secular characteristics may be unique to one cohort of individuals.
(31,32)
Experiences of the previous generation can operate at many 
different levels of generality. They may be speciﬁ  c to the moth-
er–child dyad (e.g. the effect of drug use during pregnancy), or may affect everyone living in a certain neighborhood (e.g. pov-erty, or exposure to an environmental toxin). All mothers and children maybe affected by a particular event, such as a periodof famine or disease, or children may be affected by theirmother’s developmental stage (e.g. children of teen mothers or elderly mothers). Models for intergenerational research have recently appeared

(33) and statistical methods have become more 
tractable.Prevention science
Prevention science uses theory about the causes of disease to gener-ate interventions, which when tested provide information not only about the effectiveness of the intervention, but also about the aeti-ology of the disease. Epidemiology traditionally divides prevention into thee categories, depending on the mean level of risk in the population of concern. Programmes available to all, like clean water, car seat belts, and parental leave programmes, are examples of primary  or universal  prevention. For example, the ‘Just Say No’ 
drug abstinence programme was introduced as a primary preven-tion for all children in school, designed to stop drug use before it began. Unfortunately, the results were neutral if not negative.
(34)
On the other hand, primary prevention with both children(35) and 
families(36) can be both effective, and suggest aetiologic pathways 
that could be explored in further research.

(34)
Secondary intervention programmes  are based on high-risk 
children, schools, or communities. Many of them are both theory-driven and scientiﬁ  cally sound. A good example of a secondary 
intervention that yields insights for epidemiology is the ‘Fast Track’ programme for aggressive children in grade school. This was based on clearly articulated theory about cognitive difﬁ  culties that could 
interact with environmental risk to produce aggressive behaviour in socially ambiguous situations.
(37) Hostile attributional bias was 
indeed found to be a partial mediator of the effect of the interven-tion on reductions in aggressive behaviour.
Once children have developed clinically deﬁ  ned psychiatric disor-

ders, interventions tend at present to focus on clinical treatment rather than tertiary prevention . T ertiary prevention programmes are 
rare. One example of proven effectiveness is Multisystemic Therapy.
(38) Given the early onset of most psychiatric disorders, this 
is clearly a vitally important area for future work.
This chapter has covered a lot of ground; from the ﬁ  rst stirrings of

This chapter has covered a lot of ground; from the ﬁ  rst stirrings of 
understanding about childhood psychiatric disorders to the possi-bility of using molecular genetics to identify gene–environment interactions that can generate psychiatric disorder. There are fuzzy boundaries between epidemiology and developmental psychopa-thology, life course epidemiology, genetic epidemiology, services research, and clinical psychiatry. It will be important to keep these boundaries pervious, to share a common language where possible, and to learn and use one another’s methods.
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Meltzer, H., Gatward, R., Corbin, T., et al. (2003). Persistence, onset, risk 
factors and outcomes of childhood mental disorders . Ofﬁ  ce for National 
Statistics, London.

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Carolina Health and Human Services Finance Commission, 
Columbia, SC.9.1.2 epidemiology of psychiatric disorder in childhood and adolescence

SECTION 9  child and adolescent psychiatry 1600
9.1.3 Assessment in child 
and adolescent psychiatry
The goals of assessment of a child/adolescent are to (1) detect 
psychopathology and its impacts on the child’s functioning in fam-ily, school, and peer domains, (2) allow appropriate intervention targets to be identiﬁ  ed and prioritized; and (3) identify relevant 
variables, including family or school factors that may inﬂ  uence 
treatment adherence.
Distinctive aspects of the psychiatric 
assessment in children
1 Parents (or other adults) ordinarily initiate and pursue the 
evaluation of the child for diverse reasons. Adult expectations for the child sometimes exceed the child’s abilities, or the adult’s own parenting or teaching style may be a poor ﬁ  t with this child. 
Some adults may seek treatment to alter the child to remedy this poor ﬁ  t.
2 Children may not be receptive to changing their behaviour.

2 Children may not be receptive to changing their behaviour. 
Children may attribute problems to others and be unable to accept their contribution to an identiﬁ  ed problem. The psychiat-
ric assessment of children requires attention to what the child wishes would change.
3 Y oung children may not trust unfamiliar adults (including 
clinicians), and adolescents may perceive the clinician as another adult imposing expectations or judgements. Multiple infor-mants
(1) are often needed to identify the child’s functioning in 
school, home, and peer domains, to identify the child’s areas of strength on which the clinician can build, and to identify others (peers or adults) able to introduce or reinforce more adaptive skills or behaviours.
4 Most DSM-IV-TR diagnoses were deﬁ  ned amongst adult sam-
ples.
(2) Efforts to consider where a particular child ﬁ  ts on the

ples.
(2) Efforts to consider where a particular child ﬁ  ts on the 
depressed mood, anxiety, and aggression axes, for example, requires attention to developmental differences in symptom expression.
5 The ability of the clinician to forge alliances with the child, the 
parent, and outside entities is essential. A breach in any of these relationships can impede treatment. Parental permission should be obtained to contact and collaborate with relevant parties.
Content of the clinical interview
Reason for referral
Who initiated this referral, their motivations, and what changes they seek is vital. Expectations of various parties may collide and must be reconciled for effective treatments to be implemented. For example, the school may seek changes in parental discipline, while parents may expect the evaluation to yield additional school services.
History of problem(s)

Parents often experience intense pain while recounting the deterio-ration or anguish of their child. Clinicians should provide parents an opportunity to describe the evolution of the problem, attending 
to the context in which symptoms emerged and occur, changes in frequency and intensity of symptoms, and their current progres-sion. The clinician should inquire directly about the functions  of 
problem behaviours, including secondary gains (e.g. tantrums diminish chore requirements, etc.). The clinician should clarify whether symptoms are specific to one functional domain or whether they pervade multiple areas of the child’s functioning at home, school, and with peers.
Past problems
Signiﬁ  cant past symptoms impairing the child should be identiﬁ  ed. 
It is especially important to understand whether symptoms have been persistent since early childhood, are intermittent, or represent deterioration from a previously better level of functioning.
Comorbid problems

Clinicians should inquire about disorders often seen in tandem. For example, bipolar disorder in children is often associated with previous attention deficit hyperactivity disorder.
(3) Screening 
instruments (such as those selectively available free of cost at web-sites such as www.schoolpsychiatry.org) can be useful to provide comprehensive information about less conspicuous symptoms.
Substance use history
Clinicians should inquire about the child’s exposure to and use of tobacco, alcohol, and illicit substances. Children may perceive that substances alleviate their distress (e.g. anxiety, depression) and ‘self-medicate.’ Clarifying impacts of substances on symptoms may yield intervention points attractive to the child.
Previous treatment(s)

Chronological assessment of past treatments may reveal strategies adaptable to the current problem. Past treatment history may suggest treatment modalities (in)tolerable to this patient (and family). Medication trials, counselling, hospitalizations, or alterna-tive treatments should be explored.
Developmental history
Parents may vary in their recollection of their child’s attainment of developmental milestones. Review of earlier videotapes of the child may improve the reliability and completeness of reports regarding the sequence of the child’s growth.
The child’s development regulating sleep, eating,  and toileting
should be investigated. Attained skills may suddenly be lost, some-times signalling the importance of emotional events at particular times. Eating behaviour has become complicated as both hunger and obesity increase risks of psychopathology.
(4,5)
Psychomotor development  includes standing, walking, running,

(4,5)
Psychomotor development  includes standing, walking, running, 
throwing, hopping, and playing sports or musical instruments. How the child fares at sports may clarify psychomotor skills. Fine motor and gross motor skills may not be congruent.
Cognitive development  refers to the child’s acquisition of thinking 
skills. Speciﬁ  c inquiry concerning speech development, reading, 
writing, and math skill progression may reveal global or speciﬁ  c 
Interpersonal development  refers to how the child interacts with 
others, particularly family members and other children and adults.

1601
Stability of relationships, numbers of friends, types of activities 
shared, and expectations of peers often reveal sources of difﬁ  culty 
or maladaptive patterns.
Emotional development  and temperament  reveal the child’s 
capacity to recognize his or her own mood state and to self-soothe or regulate negative affect. Prevailing moods can be described by parents, who may also detail past suicidality, irritability, speciﬁ  c 
fears and anxieties, and conditions associated with the child’s happiness and pleasure.
The child’s moral development  indicates whether conscience or 
moral values are too lax, too harsh, overly focused on particular areas, or uneven and out of proportion to daily events. The child’s ability to recognize impacts of decisions on others, and to acknowl-edge and correct mistakes provides clarity about the child’s 
strengths and limitations. The child’s religious and cultural/ethical

strengths and limitations. The child’s religious and cultural/ethical 
views and practices also shape this area, and may guide treatment interventions.
Trauma  may impact or even arrest development. Investigation of 
actual events (such as documented abuse), but also of events per-ceived traumatic by the child and family may shed important light on the child’s behaviours and patterns of relating to others. Events surrounding the trauma, disclosures to others, and reactions of adults are also important for the clinician to recognize and address.
Harmful behaviour , towards self or others, may reveal 
important developmental progressions that warrant intervention. Head-banging may reveal sensory disturbances, thoughts or comments about death may reveal suicidality, and self-harmful acts such as self-mutilation or cutting may reveal primitive coping mechanisms.
(6) Harmful acts towards animals or people may

(6) Harmful acts towards animals or people may 
indicate needs for monitoring while other diagnostic or treatment interventions occur.
Few psychiatric disorders appear transmitted exclusively genetically. Many parents fear that their other child may be destined to suffer psychopathology when a family member manifests a disorder, so clariﬁ  cation of contributions to expression of disorders can reduce 
unwarranted fear, guilt, and distress. Please refer to Chapter 6.3.8 for more information on assessment of family functioning.
Divorce, separation, and single-parent  family circumstances 
may stress all family members. Even when parents part amicably, children may attempt to reunite family members. Children may exhibit symptoms even years after separations as they enter differ-ent developmental phases.
(7)
Adoption  may be a positive event for the child, and adoption

(7)
Adoption  may be a positive event for the child, and adoption 
warrant tactful attention by the clinician, including age at adoption of the child and biological parents, the involvement with biological parents, the child’s understanding of the adoption, and how the adoption is discussed at home.
Medical history
Pregnancy complications, birth difﬁ  culties, hospital stays, and 
medical illnesses requiring treatments (e.g. asthma, diabetes) should be investigated, as they increase the child’s risk for psycho-pathology.
(8) Inquiry into emergency room visits or surgeries can 
shed light on the child’s fears, or parental over/underprotective-ness. Allergies should be ascertained, as well as responses or side effects to medications, including naturopathic or homeopathic agents.Child strengths/weaknesses
Interests, hobbies, and talents  of the child should be obtained from

Interests, hobbies, and talents  of the child should be obtained from 
the child and parents. Parents may have aspirations the child does not share, or the child may have fantasies beyond apparent abilities. In most cases, though, the child will have some identiﬁ  able inter-
ests or abilities that serve as potential points of connection with peers and adults (including clinicians).
The child’s media diet
Children are exposed to television, music, videos, electronic games, cell phones, e-mail and instant messaging, personal digital assistants, etc. It is important to clarify which media the child uses, how much time each day is spent with these various media, and what consequences these media have on the child (e.g. in response to watching action TV show the child becomes more violent versus has developed interest in Asian food through watching cooking programmes).
(9) The degree of parental awareness and appropriate

(9) The degree of parental awareness and appropriate 
limit-setting regarding TV , video games, and instant messaging may warrant intervention.
Mental status examination (MSE)
The MSE must be adjusted for children (see Fig. 9.1.3.1). The MSE includes a clinical description of the child’s appearance, mood, sensorium, intelligence, and thought content and process. Much of 
the MSE takes place implicitly as the clinician interacts and observes 
the child during the child and family interviews.
Structure of the clinical interview
Preparatory phase of the child interview
Unlike regular pediatric check-ups, the psychiatric evaluation usually occurs because of prominent symptoms often perceived as embarrassing by the parents or the child. A phone call before the interview by the clinician or staff can clarify the structure of the interview, the collaboration anticipated to devise solutions, and the opportunity for parents to provide any conﬁ  dential informa-
tion to the clinician.

The parent interview
The parent interview can be complicated by parental ambivalence about having a child evaluated by a psychiatrist, fears of loss of control or criticism, or parental shame or embarrassment about perceived parenting faults. The clinician should remain sensitive throughout the interview to parent vulnerabilities. T echniques to help parents overcome such obstacles during the interview are summarized in Fig. 9.1.3.2.
The developmentally sensitive clinical interview 
of the child
The interview process and wording of questions must be tailored 
to ﬁ t with the child’s understanding.(10) The child may not under-
stand terms necessary to answer questions accurately. The child may also provide misleading answers to shield other family mem-bers, to protect against acknowledging some perceived failing, or to address circumstances if the child fears it might entail placement out of the home. Please refer to Chapter 9.1.1 for more speciﬁ  c

information for obtaining reliable information during the child interview.9.1.3 assessment in child and adolescent psychiatry

SECTION 9  child and adolescent psychiatry 1602
Fig. 9.1.3.1 The mental status examination in children.Category Components What to Assess
Appearance Physical Appearance Gender; ethnicity; age (actual and apparent); cleanliness and   
  grooming, hair/clothing style, presence of physical anomalies,     indicators of self-care and parental attentiveness 
 Manner of Relating to  Ease of separation from parent, guardedness, defiance, eagerness  
 Clinician and Parents to please, flirtatiousness
 Activity Level Psychomotor retarded to agitated, sustained or episodic, goal-oriented
  or erratic; coordination, unusual postures or motor patterns (e.g., tics,  stereotypies, compulsions, catatonia, akathisia, dystonia, tremors)
 Speech Fluency (including stuttering, cluttering, speech impediments), rate,  
  volume, prosody
Mood Current Affect Predominant emotion and range (constricted to labile) during the

Speech Fluency (including stuttering, cluttering, speech impediments), rate,  
  interview, and appropriateness to content (e.g., giggles while talks  about sibling’s illness); intensity; lability
 Persisting Mood Predominant emotion over days/weeks; whether current affect   
  unusual or consistent with mood; whether mood reactive to situations    or same across range of situations
 Coping Mechanisms and How child manages conflict or distress, age-appropriateness of   
 Regulation of Affect responses to and dependency on parents; sexual interests, impulses,    aggression; control or modulation of urges (finding alternative or     socially appropriate means of satisfying urges); how deals with     frustration or when anxious
Sensorium Orientation Self (name), place (town, State), time (awareness of morning, day of

Sensorium Orientation Self (name), place (town, State), time (awareness of morning, day of  
  week, month, year varies by age), situation (why at this appointment)
Intellect/ Attention Need for repeating, how long sustained on activity, degree to which  
Cognition  child shifts from activity to activity, distractibility (to outside noises,    etc.)
 Memory Immediate (repeat numbers, names back), short-term (recall 3   
  objects at 2 and 5 minutes), long-term (recall events of past week) 
 Intelligence; Fund of Age-appropriate recognition of letters, vocabulary, reading, counting,  
 Knowledge computational skills; age-appropriate knowledge of geography,     history, culture (celebrities, sports, movies, etc.); concrete to abstract    thinking, ability to classify and categorize
 Judgment Best assessed after rapport established, as initially minimization or

Judgment Best assessed after rapport established, as initially minimization or 
  denial more common); what would do if found stamped envelope next    to mailbox, fire started in theater, say if saw man with big feet
 Insight Ability to see alternative explanations, others’ points of view; locus of
   control (internal v. external); defense mechanisms 
Thought Process : Coherence  Logical, goal-directed, circumstantial or tangential (consider   
  age-appropriateness), looseness of associations, word salad     (incoherent, clanging, neologisms)
 Process : Speed  Mutism, poverty of thought (long latency, thought blocking), poverty  
  of content (perseveration), racing thoughts, flight of ideas
 Perceptions Altered bodily experiences (depersonalization, derealization),   
  misperception of stimulus (illusion), no stimulus (hallucination :

Perceptions Altered bodily experiences (depersonalization, derealization),   
  misperception of stimulus (illusion), no stimulus (hallucination :   
  auditory [psychosis > PTSD > organic causes], visual [substance    use, delirium], olfactory (neurological, seizure disorder] gustatory    [from medicine side effects])
 Content Obsessions (ego-dystonic), delusions (ego-syntonic), thoughts of  
  harm to self or others (magical thinking, or fears at night often age    appropriate)

1603
The child’s understanding of the psychiatric interview
The child and parent are usually seen together at the beginning of 
the child psychiatric interview to put the child at ease. Once com-fortable, the child usually can tolerate the parents leaving the room. Transitional objects (books, electronic devices from home) may ease these transitions. Inquiring about what the child believes par-ents, teachers, or other adults want to be different as a result of this interview often elucidates what the child recognizes about others’ perspectives, and also facilitates the child projecting thoughts or fantasies about this evaluation.
Adolescents  sometimes fear parents will skew the interview by 
telling their ‘version’ ﬁ  rst to get the clinician to side against the adolescent.
(11) Meeting brieﬂ  y with the parent and adolescent to 
clarify objectives, and then meeting with the adolescent alone at length may enhance an alliance with an adolescent. During this

clarify objectives, and then meeting with the adolescent alone at length may enhance an alliance with an adolescent. During this 
initial segment the clinician can clarify the plan to meet alone with 
parents after meeting with the adolescent to review birth history, developmental milestones, and family.
Adolescents may resist answering questions or participating. 
Clinicians can identify the adolescent’s priorities and side with those that are reasonable, or identify what the adolescent needs to do to satisfy parents so that the adolescent no longer needs to see a psychiatrist. Clinicians may also decrease resistance by inquiring ﬁ rst about the adolescent’s interests, strengths, musical preferences, 9.1.3 assessment in child and adolescent psychiatry
1 Forming a clinical alliance with parents

(a) Facilitating Narrative History  Open-ended questions allow parents control, and can be followed with narrow questions to fill in needed    details.  Using the parent’s own words can help parents feel heard. (b) Finding Common Themes/Patterns   Inquiry into problems or conflicts the child has with other adults, peers, or unfamiliar others may illuminate    patterns of the child’s behavior that play out in a variety of settings, decreasing parents’ anxiety that they    alone provoke the child’s problem. (c) Finding Good Intentions Gone Awry  Parents may feel ashamed of past parenting efforts done in desperation.  Acknowledging the parent’s good intention leading to a misguided effort can diminish self-reproach.  For    example, a parent’s harsh response often belies a fear about the child’s future behavior, so identifying the    fear and then examining alternative responses can be productive).  (d) Partnering with Parents (Clinician as “partner” in decision-making process)

the child’s future behavior, so identifying the    fear and then examining alternative responses can be productive).  (d) Partnering with Parents (Clinician as “partner” in decision-making process)  Clinicians increasingly serve as partners, outlining several appropriate treatments, risks, and side effects,    and helping parents to choose and invest in preferred treatments.  If parents propose treatments the    clinician regards as unhealthy or unproven, the clinician can identify potential risks of such treatments to    minimize risks to the child. (e) Clarifying Expectations of the Evaluation  Parents sometimes have unrealistic fantasies about what the evaluation will accomplish. Inquiring early    about what the parent hopes will be accomplished by this evaluation can reveal such expectations and    fantasies, which the clinician can realistically address. For example, parents may believe the evaluation can    definitively prove the child had been abused by someone. At the other

and    fantasies, which the clinician can realistically address. For example, parents may believe the evaluation can    definitively prove the child had been abused by someone. At the other extreme, parents may fear that the    clinician will tell them that their child will never be normal, will require institutionalization, or ultimately harm    others.2 Eliciting Sensitive Information (a) Providing the Parent Opportunities to Convey Sensitive Information  Apprising parents of times and methods to convey information can provide appropriate mechanisms for    sharing of information. (b) Revisiting Sensitive Information at Safer Points  If parents resist disclosing information, the clinician should not force answers (as they are more likely to be    inaccurate or incomplete), but rather proceed to less distressing information. (c) Explaining the Purpose of Sensitive Information  Some parents may need to understand the underlying reasons for inquiring about personal information. For

to less distressing information. (c) Explaining the Purpose of Sensitive Information  Some parents may need to understand the underlying reasons for inquiring about personal information. For    example, the clinician may need to explain the need to inquire about relatives to clarify genetic contributions    to the child’s difficulties. (d) Describing How Sensitive Information Will Be Reported  Parents are sometimes fearful that details of embarrassing past parental personal problems may be    included in reports to be seen by others.  Parents may fear that marital conflict information might be used to    alter custody arrangements, or symptoms in a report that could jeopardize their child’s future educational or    occupational pursuits.  Clarifying that general information will be provided (“history of substance abuse on    maternal side”) rather than specifics and that parents will be able to review reports whose release they    authorize can diminish resistance to sharing sensitive

(“history of substance abuse on    maternal side”) rather than specifics and that parents will be able to review reports whose release they    authorize can diminish resistance to sharing sensitive information.3  Handling Discrepant Reports  (a) Contextualizing Points of View  Differences between observers’ descriptions of a child’s behavior have several potential sources. For    example, teachers sometimes report very different presentations than parents.  Examining what precipitates    the child’s problem, and how it expresses itself in different environments may allow clinicians to borrow    effective strategies across environments without “blaming” adults.   (b) Aligning Different Perspectives  When parents or adults exhibit conflict during the psychiatric evaluation, the clinician may continue to    refocus adults to the child’s needs. For example, the clinician may encourage “middle ground” approaches    to increase consistency between environments.

SECTION 9  child and adolescent psychiatry 1604
rather than focusing on their ‘problems,’ as adolescents are devel-
opmentally struggling with their identity, and may resist ﬁ  tting into 
the ‘psychiatric patient’ category.
Developmentally sensitive techniques for 
the psychiatric interview
Four categories of techniques are commonly employed in these 
interviews. Engagement  techniques are often required to put the 
child at ease so that the child will provide accurate clinical infor-mation. Projective  techniques allow the child to reveal underlying 
themes or issues which cannot be verbalized directly. Direct ques-
tioning  techniques clarify particular points needed to distinguish 
disorders, contributions to the child’s problems, and intervention options. Interactive  techniques clarify how the child relates to, as 
well as accepts or integrates input from, others.
Techniques to engage the child

Child psychiatrists often provide toys or objects for patients in the waiting room and ofﬁ  ce. Toy ﬁ  gures, puppets, and ‘relationship-
oriented’ toys may ease the child into the interview. Generic toy ﬁ gures are usually preferable, since they are more likely to evoke 
the child’s speciﬁ  c themes and concerns rather than ‘scripts’ based 
on TV shows or movies. Tasks framed as ‘games’ or active (e.g. drawing a house or family) often help the child transition into the psychiatric interview. By allowing the child to direct the content, the interviewer can follow the sequence of the child’s concerns, note themes that emerge, and observe the points at which a child avoids or shifts to a new topic.
With adolescents , efforts to indicate familiarity with contempo-

rary adolescent tastes (music, movies, terms, etc.) can be perceived ingenuine by the adolescent. Instead, clinicians may inquire about current interests, musical preferences, and current adolescent values from a curious, ‘help me understand it’ perspective, rather than from one of ‘trying to be hip.’ Manipulable items (squeeze balls, modelling clay, ﬁ  nger cuffs, cards, etc.) may allow adolescents a 
socially acceptable option for keeping their hands busy so that the interview feels less like an interrogation.
Projective techniques
Projective techniques may help the child express concerns indirectly, 
so that anxiety about signiﬁ  cant fears, telling family secrets, or 
betraying loyalties is minimized. Common projective techniques

betraying loyalties is minimized. Common projective techniques 
include having the child draw a picture of him- or herself or family doing something. For pictures of the child, body details including sizes of appendages or body parts and articulation (ﬁ  ngers, toes), 
relative size of the ﬁ  gure to the page, and frequent erasures can all 
reveal underlying issues of anxiety, perceived agency to address difﬁ culties, or needs to control the environment. Depictions of the 
self as non-human, grotesque, imbued with super powers, or of the opposite gender may provide clues about the child’s self-image and underlying wishes. The relative size and placement or omission of family members in a family drawing may illuminate the child’s feelings about family relationships. Aggressive or sexual themes may be revealed in drawings.
Verbal projective techniques can similarly yield important infor-

mation. Asking what animal or character (TV/movie star, cartoon, superhero) the child would most like to be, or whom the child would take along to a deserted island, or asking what the child would do with three magic wishes often allow underlying issues to 
emerge. Wishes may reveal basic needs, such as food or a safe place to live, or longings for parents to reunite or for the return of a departed friend. Wishes sometimes reveal speciﬁ  c desires, such as 
‘not to have tics anymore,’ or ‘never to get teased.’ Very general or 
altruistic wishes, such as ‘world peace’ or ‘to live in a big house with lots of money’ warrant further exploration, such as ‘Are there par-ticular ﬁ  ghts you would especially like to stop?’ or ‘Who else would 
live there?’ and ‘What would you do ﬁ  rst with lots of money?’
Projective techniques may help adolescents  to reveal and share

Projective techniques may help adolescents  to reveal and share 
emotionally signiﬁ  cant concerns with the clinician. Inquiries into 
favourite, or most disliked, movies, television characters, political or historical ﬁ  gures, musicians or artists, or sports ﬁ  gures, all allow 
elaboration of the teenager’s ideas in displacement. Adolescents less distrustful of the clinician may readily speak about their own social 
longings or anxieties regarding friends at school. Adolescent resis-

tances are often revealed by reluctance to divulge names of friends, or even questions about why the clinician needs to know this information. If resistance is detected, questions about what the adolescent most admires about a character, or what the adolescent imagines this character would do in given situations may reveal the adolescent’s perceptions. Asking the adolescent about the different cliques or groups at school and his or her relationship to them provides useful information about the teen’s self-image. Similarly, questions about what the adolescent sees as fair or would most like to change about school or the world often reveals underlying concerns and issues.
Direct questioning

Direct questioning can specify symptoms or events, clarify how the child sees the world and functions within it, and follow-up on material from other parts of the evaluation. Asking the child to describe friends (‘T ell me about your best friend.’), siblings, or parents, is preferable to ‘Do you get along with your brother?’ Open-ended questions such as ‘What sorts of things make you mad/afraid/happy?’ and ‘What do you daydream about?’ are simi-larly preferable to ‘Do you get mad?’ or ‘Do you ever daydream?’
Anchoring direct questions to major events may help children 
provide more accurate answers. For example, ‘Did that happen before or after your birthday?’ or ‘How has that (problem) been since school ended?’ improve respondent accuracy.
Substance abuse, sexuality, and risky behaviours are often 
assessed through direct questions. The clinician can use simple 
questions, such as ‘Substance use?’ that allow signiﬁ  cant latitude,

questions, such as ‘Substance use?’ that allow signiﬁ  cant latitude, 
and then focus in further, contingent on the child’s responses. For example, the clinician may hear ‘No, I don’t do any of that any-more,’ which could then be followed by ‘What led to that decision?’ and then proceed back to when and what substances were used. Similarly, sexuality can be assessed by gentle direct questions that do not prematurely close off response options, such as ‘Have you had romantic feelings towards another? How did that go?’ (rather than ‘Have you had a boyfriend yet?’). Adolescents may fear the interviewer will be disapproving, so questions like ‘romantic feel-ings towards anyone’ are preferable to ‘are there any girls you like?’
(12) Finally, direct inquiries into risky behaviours (stealing,

(12) Finally, direct inquiries into risky behaviours (stealing, 
vandalism, assaults, gambling, etc.) often require general questions such as ‘Have you done anything that you now look back on and think was dangerous?’ before proceeding to speciﬁ  c questions (e.g. 
‘Have you ever stolen anything? Have you ever been beaten up?

1605 9.1.3 assessment in child and adolescent psychiatry
Beat up someone else?’). Suicidal risk behaviours may be mini-
mized or trivialized, so additional questions to examine fantasies 
about impacts of the suicide on family and friends or value contra-dictions may be needed to clarify suicidality risks.
(13)
Interactive techniques
Throughout, the clinician observes how the child relates to another person and what feelings or reactions this child elicits. How the child reacts to a new person, sustains interactions, and terminates the interview often reveal patterns important in the child’s larger social life. The clinician can evaluate more complex social interactions during transitions (‘It’s time to put these toys up in the box.’) and during games. Short games (tic tac toe) are useful since the clinician can quickly detect the child’s response to winning, tying, and losing.
Adolescents  employ more complex patterns, often speciﬁ  c to a

Adolescents  employ more complex patterns, often speciﬁ  c to a 
subgroup to which they now belong, so clarifying what clothing symbols represent, meanings of confusing terms, and values espoused by subgroups can clarify how the adolescent relates to others. The clinician should observe provocative comments, often used to titrate space between the clinician and the adolescent, or to 
reject others ﬁ  rst.
Concluding the interview
Ending collaboratively increases the likelihood that the child will 
feel positive about subsequent encounters with clinicians, includ-ing treatment. Questions such as ‘Are there other things that would be important for me to know about what you’re like or how things have been for you?’ or ‘What else have I not asked about that is important?’ facilitate this process.
The child may be curious about what the clinician will say and

The child may be curious about what the clinician will say and 
to whom. The interview is one piece of a larger evaluation, so the clinician may need to clarify that other testing, conversations with others, or additional meetings may be needed. Discussing ﬁ  ndings 
(including treatment recommendations) with parents is usually advisable since parents may disagree with the clinician’s conclu-sions or resist suggested interventions (e.g. medication, school placement, etc.).
Conﬁ  dentiality is one of the most challenging issues surround-
ing child psychiatric interviews, especially with adolescents. Describing to the adolescent what will be told to speciﬁ  c others 
is helpful, as well as what information will not be revealed (e.g. specific details about substance abuse or sexual behaviours). Parents and the child should be told explicitly that conﬁ  dentiality 
does not extend to situations that pose a clear danger to the child

does not extend to situations that pose a clear danger to the child 
or others. In cases where dangerous content emerges (e.g. the child describes obtaining bullets to frighten a peer), the clinician should clarify with the child how they will tell appropriate others, 
preferably together.
Neuropsychological testing
Patients may have subtle or complicated difﬁ  culties processing 
certain types of information. Consultation with a pediatric neuro-psychologist may clarify appropriate tests to address persisting diagnostic questions. Clinicians should recognize that young patients may not be ‘interested’ in testing tasks, so scores should be interpreted cautiously, with input from the person who did the testing, when the clinician discusses ﬁ  ndings with families.
Laboratory evaluation in the child 
psychiatric evaluation
Few definitive clinical tests identify specific child psychiatric

Few definitive clinical tests identify specific child psychiatric 
disorders. Laboratory testing remains useful when symptoms and physical ﬁ  ndings suggest a particular disorder. Collaboration 
with the primary pediatric care provider may guide decisions about possible further medical consultations (e.g. audiometric, genetic, neurological, speech, etc.) or diagnostic tests (e.g. blood tests, neuroimaging, sleep studies).
Testing in speciﬁ  c childhood disorders
Laboratory testing yields ﬁ  ndings that alter the working diagnosis 
in approximately 1 per cent of cases, and the yield for laboratory abnormalities, without the presence of other supportive physical ﬁ ndings, remains less than 5 per cent.
(14) Laboratory tests com-
monly considered are summarized in Table 9.1.3.1. Specialized technologies, such as positron emission tomography (PET), single photon emission computerized tomography (SPECT), functional

monly considered are summarized in Table 9.1.3.1. Specialized technologies, such as positron emission tomography (PET), single photon emission computerized tomography (SPECT), functional 
Table 9.1.3.1  Laboratory tests to consider in childhood psychiatric disorders
Disorder
Lab test MR/PDD Mood Psychosis OCD tics Substance 
abuseEating 
disorders
Chromosomal testing X X
Wood’s (UV) lamp XMonospot X
Thyroid XX X
Lyme titre X
CBC X X X X XSerum chemistry X X X X XLead level XThroat culture antistreptolysin O antibody (ASO), antideoxyribonuclease B titres X
Urine drug screen X X X
Cerebrospinal ﬂ  uid analysis X XNeuroimaging X
EEG X

SECTION 9  child and adolescent psychiatry 1606
MRI (fMRI), and brain electrical activity mapping (BEAM) remain 
attractive research tools at this time in child psychiatry.
Recommended Websites:
www.aacap.org: the home site for American child psychiatry; includes 
current practice parameters for various psychiatric disorders.
www.schoolpsychiatry.org: rating scales, school interventions for psychiatric 
symptoms.
Baron, I.S. (2004). Neuropsychological evaluation of the child . Oxford, 
New Y ork.
Martin, A. and Volkmar, F.R. (eds.) (2007). Lewis’s child and adolescent 
psychiatry: a comprehensive textbook  (4th edn). Lippincott, Williams, & 
Wilkins, Philadelphia.
Mash, E.J. and Barkley, R.A. (eds.) (2007). Assessment of childhood disorders
(4th edn). Guilford, New Y ork.
Rutter, M. and Taylor, E.A. (eds.) (2002). Child and adolescent psychiatry
(4th edn). Blackwell, Oxford.
 1. Ferdinand, R.F., Hoogerheide, K.N., van der Ende, J., et al. (2003). The

 1. Ferdinand, R.F., Hoogerheide, K.N., van der Ende, J., et al. (2003). The 
role of the clinician: three-year predictive value of parents’ , teachers’ and clinicians’ judgment of childhood psychopathology. Journal of 
Child Psychology and Psychiatry, and Allied Disciplines ,44(6), 867–76.
 2. Patel, V ., Flisher, A.J., Hetrick, S., et al. (2007). Mental health of young 
people: a global public-health challenge. Lancet ,369(9569), 1302–13.
 3. Masi, G.P .G., Millepiedi, S., Mucci, M., et al. (2006). Developmental 
differences according to age at onset in juvenile bipolar disorder. Journal of Child and Adolescent Psychopharmacology ,16(6), 679–85.
 4. Weinreb, L., Wehler, C., Perloff, J., et al. (2002). Hunger: its impact on 
children’s health and mental health. Pediatrics ,110(4), e41.
 5. Vila, G., Zipper, E., Dabbas, M., et al. (2004). Mental disorders in obese

 5. Vila, G., Zipper, E., Dabbas, M., et al. (2004). Mental disorders in obese 
children and adolescents. Psychosomatic Medicine ,66(3), 387–94.
 6. King, R.A., Ruchkin, V .V ., and Schwab-Stone, M. (2003). Suicide and 
the continuum of adolescent self destructiveness: is there a connection? 
In Suicide in children and adolescents  (eds. R.A. King and A. Apter). 
 7. Wallerstein, J.S. and Blakeslee, S. (2000). The unexpected legacy of 
divorce: a 25 year landmark study . Hyperion, New York.
 8. Indredavik, M.S., Vik, T., Heyerdahl, S., et al. (2004). Psychiatric 
symptoms and disorders in adolescents with low birth weight. Archives 
of Disease in Childhood. Fetal and Neonatal Edition ,89(5), F445–50.
 9. Pataki, C., Bostic, J.Q., and Schlozman S. (2005). The functional 
assessment of media in child and adolescent psychiatric treatment.

9. Pataki, C., Bostic, J.Q., and Schlozman S. (2005). The functional 
assessment of media in child and adolescent psychiatric treatment. 
Child and Adolescent Psychiatric Clinics of North America ,14(3), 
555–70.
10. Lewis, M. (ed.) (1991). Psychiatric assessment of infants, children, and 
adolescents . Williams and Wilkins, Baltimore.
11. King, R.A. and Schowalter, J.E. (2004). The clinical interview of the 
adolescent. In Textbook of child and adolescent psychiatry  (3rd edn) 
(eds. J.A. Wiener and M.K. Dulcan), pp. 113–16. American Psychiatric 
12. King, R.A. (1997). Practice parameters for the psychiatric assessment 
of children and adolescents. American Academy of Child and Adolescent Psychiatry. Journal of the American Academy of Child and 
Adolescent Psychiatry ,36(Suppl. 10), 4S–20S.
13. Galvin, M.R., Fletcher, J., and Stilwell, B.M. (2006). Assessing the

13. Galvin, M.R., Fletcher, J., and Stilwell, B.M. (2006). Assessing the 
meaning of suicidal risk behavior in adolescents: three exercises for clinicians. Journal of the American Academy of Child and Adolescent 
Psychiatry ,45(6), 745–8.
14. Challman, T.D., Barbaresi, W.J., Katusic, S.K., et al. (2003). The yield 
of the medical evaluation of children with pervasive developmental disorders. Journal of Autism and Developmental Disorders ,33(2), 187–92.9.1.4 Prevention of mental 
disorder in childhood and other public health issues
Over the last two decades advances in psychiatric classiﬁ  cation 
systems and screening tools have allowed the global and national burden of mental disorder to be described with the ﬁ  rst large-scale 
epidemiologic studies. The World Health Organization’s World 
Health Report 2001  estimated that over 450 million individuals suf-

fer from mental disorders, and that psychiatric disorders ranked as 5 of the top 10 causes of disability in the global population.
(1)
Studies speciﬁ  cally of psychiatric disorders in children report that 
between 3 per cent and 18 per cent of children have a clinically signiﬁ  cant psychiatric disorder, a number far exceeding those with 
access to treatment.
(2) A recent study which included data on age of 
onset found that 50 per cent of psychiatric disorders had their onset by age 14, and 75 per cent by age 24.
(3) Treatment on this scale is

(3) Treatment on this scale is 
unlikely to ever be feasible, even if available methods were more effective and less risky than those currently available. Preventing mental health disorders from occurring is an alternative to decrease the extent of this public health problem. However, if a key charac-teristic of prevention is acting prior to onset of a disorder, the early age of onset for most mental disorders indicates intervention must occur during long before adulthood.
Neuroscience has contributed evidence that longitudinal trajec-

tories of brain development are affected by a combination of genetic and environmental factors. Neuroimaging studies have shown dynamic changes in brain structure and function continu-ing through childhood and adolescence, and geneticists have found that gene expression is highly dependent on environmental condi-tions. These ﬁ  ndings imply that the brain is still highly plastic 
during childhood and adolescence. This may confer greater vulner-ability to long-term effects of insults from trauma, substance abuse, 
or other adverse inﬂ  uences than in adulthood, but also the poten-
tial for lifelong beneﬁ  cial effects from early positive interventions.
Growing interest in the possibilities afforded by research into 
prevention in children’s mental health stimulated a series of large-scale reports and initiatives beginning in the early 1990s.
(4–7)

(4–7)
Advances in epidemiology, developmental psychopathology, and prevention science have converged to provide a framework to guide and evaluate prevention programmes. This chapter will discuss basic principles of public health and preventive medicine with application to mental health disorders in children and adolescents.
Public health and prevention: history and 
basic concepts
The goal of public health is the prevention of disease and promo-
tion of health in communities. The World Health Organization has deﬁ ned health  as ‘a state of physical, mental and social well-being 
and not merely the absence of disease or inﬁ  rmity’ ,
(8) and mental 
health  as ‘a state of well-being in which the individual realizes his or

1607
her own abilities, can cope with the normal stresses of life, can work 
productively and fruitfully, and is able to make a contribution 
to his or her community’ .(1) Public health differs from clinical 
medicine in that it addresses health-related matters on the level of populations rather than individuals. Public health activities include assessment of the health status and risk factors within a commu-nity through epidemiology, and population-focused interventions such as supporting the practice of preventive medicine, health education and behavioural modiﬁ  cations, creating and enforcing 
measures to maintain a healthy environment, and working to increase support for public health initiatives within the political sphere. In countries without universal access to health care public health ofﬁ  ces may also act as providers of medical treatment for 
individuals without other means of access.
(9)
Communities have acted to support the health of their members

(9)
Communities have acted to support the health of their members 
throughout history.(10) Common concerns for most societies have 
included control of epidemics, public sanitation, and promotion of personal hygiene, although the forms of public health interven-tions have varied depending on societal values, conceptions of the causes of ill health, and available resources. The health risks posed by the large-scale urban poverty and overcrowding associated with the industrial revolution helped to stimulate the growth of modern public health organizations, whose concerns eventually broadened to include issues such as workplace safety and regulation of the production of foods and medicines. Public health interventions changed to reﬂ  ect advances in the understanding of disease pro-
cesses, for example moving from general notions of the value of sanitation to focusing on speciﬁ  c infectious agents. Measures such

cesses, for example moving from general notions of the value of sanitation to focusing on speciﬁ  c infectious agents. Measures such 
as widespread vaccination and regulation of sanitary conditions have been so effective in developed countries that the focus of 
public health in these areas has shifted to chronic disorders such 
as heart disease and hypertension. Although emotional and behav-ioural issues have always been a concern of communities, system-atic intervention to prevent mental disorders has lagged behind other disorders, in large part because of the lack of consensus regarding the nature of these problems or even how to classify them. A key factor in the advances in public mental health of the past several decades has been progress in epidemiology of mental health disorders.
(9)
Epidemiology in public mental health
Incidence and prevalence
Epidemiology provides information about the incidence  of a

(9)
Epidemiology provides information about the incidence  of a 
condition, meaning the number of new cases, which arise during a certain period of time, and its prevalence , meaning how many indi-
viduals have the condition during a certain period. The goal of pre-vention is to decrease a condition’s incidence, i.e. prevent new cases from occurring, while successful treatment results in the decrease of the prevalence. Mental health disorders have presented challenges to epidemiology on several levels. In order to determine how many cases of a certain condition exist within the population, it is necessary to know how to deﬁ  ne a case, but this is far from straight-
forward in the realm of mental health. Classiﬁ  cation of medical 
disorders tends to evolve from symptom-based to mechanism-based as the links between a speciﬁ  c pathophysiology and the 
observed signs and symptoms are established. The lack of knowl-

edge about the mechanisms producing cognitive and behavioural 
symptoms means that classiﬁ  cation of mental disorders still relies upon descriptions of constellations of symptoms. The International 
Classiﬁ  cation of Disease version 10 (ICD-10 ),
(11) and its United 
States counterpart the Diagnostic and Statistical Manual TR-IV
(DSM-TR-IV ),(12) are the results of iterative attempts by experts in 
the ﬁ  eld to create meaningful classiﬁ  cations of psychiatric disor-
ders based upon such observations in conjunction with applicable considerations of length and severity of illness, age of onset, and risk factors. This work has provided the standardized terminology 
that made possible the ﬁ  rst large-scale epidemiologic descriptions

that made possible the ﬁ  rst large-scale epidemiologic descriptions 
of mental disorders. However, problematic issues pertinent to epidemiology remain, including questions regarding the relative merits of categorical versus dimensional classiﬁ  cation systems; how 
to interpret the high rate of comorbidities for several disorders; and how best to account for individuals who have subthreshold symptoms, including how to determine the starting point of a disorder. It is not uncommon for individuals who have come to meet criteria for a mental health disorder such as schizophrenia or depression to have had a preceding period of subthreshold ‘pro dromal’ symptoms, but healthy individuals also have occasional subthreshold symptoms that resolve without intervention. Unfortunately this differentiation often cannot be determined except retrospectively, despite the fact that there may be different implications for epidemiologic and preventive efforts.

The question of how symptoms change over time gains addit ional 
relevance when attempting to describe the epidemiology of mental health disorders in children and adolescents. As described in more detail elsewhere in this volume,
(13) the science of developmental 
epidemiology has arisen as a respo nse to the reco gnition that mental

epidemiology has arisen as a respo nse to the reco gnition that mental 
disorders may manifest in different ways over the lifespan, and that certain types of symptoms at one age may indicate that an individual is at high risk for developing a different disorder at a later stage of maturation. Risk factors may also have differing impact depending on an individual’s developmental stage. Function may appear impaired if children are developing slowly in compari-son with their peers, and it must be decided when this is normal variation and when it should be considered pathological. An additional layer of complexity in epidemiology in paediatric popu-lations is the incorporation of information from additional informants such as parents and/or teachers, and determining how to evaluate the relationship of symptoms to particular contexts.

Epidemiology is also used to assess for the presence of risk factors. Fixed risk factors  are those that cannot be altered, such as genotype. 
Malleable risk factors  are susceptible to intervention, such as expo-
sure to lead-based paint or domestic violence. Causative risk factors
are those with known relationships to a particular outcome, and are of particular interest to prevention because they represent potential points of intervention. Protective factors  instead decrease 
the risk of an adverse outcome. Resilience  is a term used to describe 
an individual’s ability to do well despite exposure to a typically high-risk situation.
Effective intervention to decrease risk factors or increase protec-
tive factors requires determining how these factors relate to each 
other and to the targeted health issues. The ultimate goal is a chain 
of causative steps leading from risk factor to outcome, but epide-miological data itself may provide sufﬁ  cient guidance for action.

of causative steps leading from risk factor to outcome, but epide-miological data itself may provide sufﬁ  cient guidance for action. 
One of the most famous examples of this was John Snow’s identiﬁ  -
cation of tainted drinking water from a particular well as the root 9.1.4 prevention of mental disorder in childhood and other public health issues

SECTION 9  child and adolescent psychiatry 1608
of a cholera epidemic in London, which he did based solely on 
epidemiological observations. Removal of the pump handle stopped the epidemic and proved that exposure was a causative risk, decades before the bacteria itself was identified. We are currently in a similar situation to Snow in regards to connecting risk factors to mechanisms for many mental health disorders, with the additional complication that mental health disorders are typically associated with combinations of a large number of indi-vidually modest potential risk factors.
Risk factors can be classiﬁ  ed in terms of how they relate to each 
other and to the speciﬁ  ed outcome,
(14) and thus what type of 
intervention if any is appropriate. Mediating  risk factors are those 
which explain how or why another factor affects the outcome; for example, the phenylketonuria enzyme mediates  the effects of the 
phenylketonuria gene on IQ.
(14) Although all causal factors are

(14) Although all causal factors are 
mediators, the reverse is not true, and experimental conditions are generally necessary to demonstrate that a particular mediator plays a causal role. A moderating  risk factor instead speciﬁ  es under 
what conditions or for whom another risk factor will affect outcome. Moderating risk factors describe populations that have differing responses to a given exposure, and may also represent potential sites of intervention to prevent an adverse outcome by reducing vulnerability or increasing resilience. A proxy  risk factor, 
also called a pseudocorrelation , is one that itself does not strongly 
predict outcome but is highly correlated to a risk factor that does. Overlapping  risk factors are those that arise from the same underly-

ing construct and are observed to equally predict outcome, be highly correlated with each other and not stand in a speciﬁ  c 
temporal relationship; these can often be combined into a single 
factor. Independent  risk factors conversely are unrelated to each 
other; they both predict outcome but without correlation or temporal precedence.
Theoretical models in prevention
The identiﬁ  cation of risk factors and their interpretation evolves 
together with theoretical models for the causes and treatments of health problems. The fundamental model used throughout public health and epidemiology is that of host-agent-environment , in 
which the host is the person affected or at risk, the agent  is the direct 
cause of disease, and the environment  includes external factors

cause of disease, and the environment  includes external factors 
which affects the host’s vulnerability to the agent and the vector by which the agent reaches the host. While this model was ﬁ  rst 
developed for infectious disease, it has been expanded to include other types of chronic non-infectious disorders.
(10) Examples of 
pathogenic agents in the latter case include nutrition, chemicals, and genes; host factors include age, sex, and lifestyle; while social or economic issues are among those potentially affecting the environment. Another dimension that has gained increased atten-tion in psychopathology is the actual transaction between the individual and environment—for example, the features of the way a child and parent interact. Intervening to remove risk factors from multiple domains simultaneously can potentially provide the most effective outcome.

Incorporating development into this model adds many challenges. 
The ﬁ  elds of developmental science and developmental psychopa-
thology arose to create as a framework for the integration of infor-mation from developmental epidemiology, neuroscience, genetics, psychology, psychiatry, sociology, and other disciplines in order to better understand the complex interplay of factors affecting the 
health of an individual throughout their lifespan.
(15) Major contri-
butions from work in this area have been establishing the impor-tance of interactions between genes and environment in determin-ing the trajectory of development, rather than attributing mental health outcome to being due entirely to one factor or the other, and the dialectical nature of the relationship between the develop-ing individual and their environment. The recognition of the importance of context in development has led to an elaboration of the different overlapping systems, or ecologies
(16) that a child

(16) that a child 
resides within and which present unique risks and opportunities for intervention.
Risk factors may be generalized, such as malnutrition and poverty, 
or more disease-speciﬁ  c, such as exposure to a particular toxin. 
Many risk factors will tend to occur together, and often risk factors have a non-linear relationship to outcomes; i.e. one or two may not signiﬁ  cantly affect outcome, while as the number goes above a 
certain level risk increases sharply for a number of disorders. An additional complexity in developmental psychopathology is the presence of multicausality and multiﬁ  nality. Multiple risks or 
disease processes may produce similar behavioural phenomena, while speciﬁ  c risk factors may be associated with a wide range of 
clinical presentations. Tracing causal paths and determining what are the factors that are mediating and moderating the relationships 
between risks and outcomes depends upon the ability to follow the

between risks and outcomes depends upon the ability to follow the 
impact of speciﬁ  c interventions over time.
The prevention research cycle and evidence-
based prevention
Although direct experimentation on human subjects to establish 
causality among the risk factors affecting developmental trajecto-ries is not in itself ethically feasible, suitably designed longitudinal controlled trials of preventive interventions can address the same goals.
(17) Recognition of the value of considering prevention 
research as an iterative process led to the formulation of the preven-
tive research cycle .(4) The steps in the cycle are: (i) identiﬁ  cation of

tive research cycle .(4) The steps in the cycle are: (i) identiﬁ  cation of 
the problem or disorder and the size of its impact on a community; (ii) review of relevant information, particularly regarding relevant risk and protective factors available data from existing preventive research programmes; (iii) design, conduct, and analysis of pilot studies, including replication at multiple sites; (iv) implementation of larger-scale trials which will provide additional information about which populations may be more or less appropriate, and how the intervention does when scaled up in size; and (v) large-scale implementation and ongoing evaluation.
The randomized clinical trial, in which individuals or discrete

The randomized clinical trial, in which individuals or discrete 
communities are randomly assigned to receive either the interven-tion under investigation, a different intervention, or no interven-tion at all, continues to be a gold standard for determining whether a prevention programme itself is responsible for observed changes and thus to establish causality. Only a randomized clinical trial can determine if the intervention actually results in prevention, i.e. evidence that new cases did not develop that otherwise would have. Some trials, particularly those for populations in which some symptoms may already be present, result in decrease of those subsyndromal symptoms. While this is not without value, it is more strictly considered treatment than prevention.

1609
The ability to make a convincing case for the value of a preven-
tive intervention is particularly important because investing in pre-vention is asking an individual or community to devote resources towards a problem that has not yet occurred. Standards for evidence-based preventions have been explicitly identiﬁ  ed to help 
with design and evaluation of studies, including criteria for when there is sufﬁ  cient grounds to move along the research cycle from 
pilot studies to large-scale ﬁ  eld trials and ﬁ  nal dissemination.
(18)
The recommendations provide guidance for appropriate statistical 
methodology and design, and emphasize the need for replication in independent samples, adequate provision of training materials for non-research personnel as the scope of the project grows, and ongoing data collection after dissemination to inform communi-ties and researchers about the impact of the intervention and direct the next iteration. They also differentiate between effectiveness ,

deﬁ ned as showing a positive result in pilot studies under highly 
controlled circumstances, and efﬁ cacy , indicating a programme is 
also able to produce results in the less-optimal conditions associ-ated with larger-scale trials.
Types of preventive interventions
Once it has been determined that a particular problem is present, and pertinent risk and protective factors have been identiﬁ  ed, it is 
necessary to determine what type of intervention is most likely to be effective. Two broad distinctions are applicable to any interven-tion. The ﬁ  rst, as implied by the host-agent-environment model, 
is whether to address the individual, their environment, or both. The second distinction concerns which portions of the population potentially at risk are to be addressed.
(19)
Primary, secondary, and tertiary prevention
The ﬁ  rst widely used public health prevention categories were pro-
posed by the Chronic Disease Commission in 1957, who classiﬁ  ed

(19)
posed by the Chronic Disease Commission in 1957, who classiﬁ  ed 
prevention as being primary, secondary, or tertiary.(20)Primary 
prevention  is aimed at the normal population and deﬁ  ned as efforts 
aimed at decreasing the incidence of new cases, such as preventing access to contaminated water supplies as illustrated by the case of John Snow. Secondary prevention  is targeted towards individuals 
who already show early signs of disease or disorder, with the aim of decreasing the prevalence of already established cases. Tertiary 
prevention  attempts to minimize the degree of morbidity associated 
with an established illness, through decreasing its duration or asso-ciated disability. Such deﬁ  nitions were a crucial step in designing 
interventions to focus on a speciﬁ  c population and problem and

interventions to focus on a speciﬁ  c population and problem and 
take into account speciﬁ  c characteristics of that situation. However, 
classifying prevention by the disease stage may require a greater understanding of how risks related to disorders than is possible for 
many conditions.
Universal, selected, and indicated prevention
An alternative classiﬁ  cation system based upon risk–beneﬁ  t con-
siderations for preventive interventions was introduced by Gordon in 1983
(21) and disseminated through the seminal Institute of 
Medicine  report in 1994.(4) Gordon proposed that the beneﬁ  t of a 
prevention programme could be assessed by comparing an indi-vidual’s risk of developing a disorder with the risk or cost of the associated intervention. In his system, prevention is classiﬁ  ed as 
universal ,selected , or indicated , depending on the degree of  identiﬁ  ed risk. Universal prevention  is applied to everyone in a

universal ,selected , or indicated , depending on the degree of  identiﬁ  ed risk. Universal prevention  is applied to everyone in a 
deﬁ ned population, and the associated interventions are optimally 
low risk, low cost, and may be administered by individuals who possess relatively little specialized training. However, universal pre-vention spends resources on a large number of individuals who would not have become ill in any case. Selective intervention  is 
aimed at individuals at above-average risk for a disorder, and antic-ipates a commensurately higher cost and intensity of intervention. Finally, indicated prevention  is for individuals who are showing 
early signs of a disorder or exhibit biological markers indicating risk; the acceptable cost and risk here would again be higher to reﬂ ect the increased need of the individual.
There are areas of similarity between the two systems, which

There are areas of similarity between the two systems, which 
has led to some confusion. The populations and goals of primary and universal prevention are comparable, but selected and indicated groups indicate individuals at increasing levels of risk but who do not yet meet criteria for a disorder, whereas secondary and tertiary address issues related to different stages of having a disorder.
Comparison of prevention and health promotion
An alternate conceptualization of how to proactively intervene to improve outcomes is health promotion , deﬁ  ned as measures 
to increase likelihood of wellness as a positive quality rather than limiting efforts to decreasing risks for a negative outcome.
(5) From 
a practical standpoint it overlaps largely with universal prevention, but the theoretical foundations and targeted outcomes differ. Although few would disagree with the potential beneﬁ  ts of promoting

health in the community, health promotion has not always been included within the scope of prevention policy due to concerns that it may dilute efforts towards risk prevention that are character-ized by more clearly deﬁ  nable and measurable outcomes. Others 
have argued that in view of the complex pathways of developmen-tal psychopathology, a less-speciﬁ  c approach is more consonant 
with our existing knowledge, and may actually be more effective over the long run to create resilience against a broader range of disorders.
(22)
Effective preventive interventions for 
children’s mental health
The degree of implementation of preventive measures for mental 
health disorders in children and adolescents depends largely on how convincingly speciﬁ  c risk factors can be demonstrated which

health disorders in children and adolescents depends largely on how convincingly speciﬁ  c risk factors can be demonstrated which 
are malleable to politically and economically feasible actions. For example, realization of the adverse effects of prenatal alcohol exposure on neurodevelopment resulted in widespread public education efforts. Other toxins such as lead-based paint have also been the focus of education and regulations to decrease children’s exposure. Vaccination programmes have signiﬁ  cantly reduced 
mental disorders associated with infectious diseases such as rubella, and programmes have been put in place to decrease risks from accidents through measures such as use of car seats and bicycle helmets.
For conditions where the core risk factors are less clearly deﬁ  ned

For conditions where the core risk factors are less clearly deﬁ  ned 
progress has been slower, but enough data has accrued over the past two decades of systematic prevention trials to be able to begin to assess the effectiveness of preventive interventions in this context. The scope of the current chapter does not allow a detailed description, and the reader is referred to relevant chapters for 9.1.4 prevention of mental disorder in childhood and other public health issues

SECTION 9  child and adolescent psychiatry 1610
speciﬁ  c disorders within this text, as well as general reviews and 
meta-analyses available elsewhere.(4,5,16,19)
Health promotion
A recent report by the World Health Organization summarized globally relevant general risk factors and the state of evidence for speciﬁ  c interventions to promote mental health and resilience.
(6)
Social, environmental, and economic factors have a major impact 
on mental health. Increasing attention is also being paid to social 
capital , a concept which broadly refers to aspects of social organiza-
tion and community norms that facilitate the ability of indivi duals to work together for mutual beneﬁ  t. General measures for health

tion and community norms that facilitate the ability of indivi duals to work together for mutual beneﬁ  t. General measures for health 
promotion include improving nutrition, housing, access to educa-tion and economic security, as well as strengthening community networks, reducing exposure to violence, decreasing substance abuse, and intervention to help with recovery from disasters. Risks for children’s mental health from the proximal family environment include adverse maternal behaviour during pregnancy, such as substance abuse, child abuse, parental mental illness, and domestic violence, and may be addressed with measures such as home-
visiting programmes for pregnant women and new mothers and 
pre-school programmes.
While the beneﬁ  ts of such general health promotion activities 
seems highly plausible, rigorous evidence of their effects on mental health allowing quantiﬁ  cation for cost-beneﬁ  t questions is difﬁ  cult to

seems highly plausible, rigorous evidence of their effects on mental health allowing quantiﬁ  cation for cost-beneﬁ  t questions is difﬁ  cult to 
come by and currently patchy, especially for larger-scale interventions. Reasons for this include the length of time necessary to see the results of these interventions, which may be much longer than the policy environment which fostered them; the large samples neces-sary, which may range from difﬁ  cult to impossible to randomize 
appropriately, and the lack of funding for this type of information-gathering. Here in particular naturalistic ‘experiments’ may be of aid, in which populations exposed to changes in risk factors or social policies are closely monitored for the impact on health outcomes.

The practical implementation of universal preventive measures overlaps largely with health promotion, despite the differences in their theoretical background and aims. Universal prevention pro-grammes have the signiﬁ  cant advantage of not conferring stigma 
upon participants, but their beneﬁ  ts are difﬁ  cult to quantify due to 
the generally small effect sizes and consequent large samples neces-sary,
(23) and they by deﬁ  nition devote signiﬁ  cant resources to indi-
viduals who likely would not have had problems regardless. Universal prevention programmes with evidence of beneﬁ  t have 
been developed for issues such as conduct disorder, anxiety, and depression. These have been primarily school-based, focusing on classroom behavioural management, social skills training, and 
cognitive strategies to help children learn prosocial behaviours 
and cope with stressful situations. Some programmes adopt a 
multimodal approach which includes parents. Universal approaches

multimodal approach which includes parents. Universal approaches 
to decrease substance abuse have had mixed results. Educational 
techniques have shown clear success in increasing the knowledge base regarding risks of substance abuse, but impact on actual usage has been harder to demonstrate outside of more comprehensive programmes targeting multiple types of risk.
(16)
Preventive measures for selected populations become more spe-
ciﬁ c to individual disorders. Children at risk for conduct disorder often come from impoverished environments with high rates of 
exposure to violence, substance abuse, and weak family and com-munity structures. Secondary preventions in these settings accord-

ingly rely more strongly on multimodal interventions which include the family. Children with a depressed parent are at increased risk for depression, and secondary interventions in this case may 
include treatment of the depressed parent in addition to cognitive therapies for the child. Stress related to difﬁ  cult transitions such 
as parental death, divorce, or unemployment are also signiﬁ  cant 
risk factors for children, and have been effectively addressed with courses of cognitive group therapy.
Indicated prevention measures, for children with early symp-
toms or biological markers of a disorder, have the narrowest scope and generally the clearest evidence of effectiveness. A seminal study in the prevention of depression was performed by Clarke and colleagues,
(24) who showed that cognitive therapy in adolescents

(24) who showed that cognitive therapy in adolescents 
with subsyndromal symptoms of depression and a depressed parent could reduce the incidence of new cases of depression compared to a control group. Schizophrenia has become a target of preventive medicine through studies showing that treatment of adolescents with early symptoms of psychosis may delay onset of a full psychotic break.
(25) Multimodal interventions have also been 
shown to be effective for children and adolescents already showing signs of increased aggressive or antisocial behaviour.
Common themes in ‘best-practice’ mental health prevention 
programmes have included the need for multimodal approaches which simultaneously address both the child and components of the environment, and the increased durability of improved out-comes when interventions are maintained for signiﬁ  cant lengths

of time. Many programmes focus on reduction of proximal risk factors rather than mental health disorders themselves as a more feasible outcome measure, although when possible it is optimal to incorporate both. When preventive research began to stratify interventions into universal, selected, and indicated, it was originally predicted that the lowest-risk individuals would benefit the most from universal-level interventions. It was instead found that 
higher-risk children actually showed the greatest response, sup-
porting the development of tiered systems in which children who did not beneﬁ  t adequately from universal measures could also be 
referred for secondary and indicated levels.
In general, meta-analyses have found that preventive pro-

grammes in mental health for selected and indicated populations have small to moderate effect sizes, similar to those seen in other areas of medicine. Anxiety and depression have shown the most consistent responses. Universal programmes have not shown sig-niﬁ cant effectiveness in meta-analyses of controlled trials, which is 
understandable given the necessary sample sizes, but has led to debate regarding the justiﬁ  cation of their claim on scarce resources.

understandable given the necessary sample sizes, but has led to debate regarding the justiﬁ  cation of their claim on scarce resources. 
Another concern is that most research has been carried out at the level of pilot studies, with much less available from large-scale trials or fully disseminated programmes. What information is available shows a tendency for a fall off in effectiveness when moving to larger-scale implementation. This suggests a need to spend more attention from the earliest stages on issues relating to dissemination such as adapting programmes for existing community infrastructure. Early collaboration with the members of the targeted community also helps to ensure relevance of a programme and consequent participation; for example parenting classes, while potentially valuable, may not attract individuals preoccupied with issues,

1611
such as safety or securing transportation. Finally, the issue of 
how to transfer preventive programmes into different settings requires much more extensive attention. Most prevention research has been done in a few of the more afﬂ  uent nations, primarily the 
United States, United Kingdom, Canada, Australia, and countries in northern Europe. Little is known about how to transfer pro-grammes or which programmes may be suitable for other less-afﬂ uent areas.
Enormous progress has been made in recognizing the scope of men-

tal health problems for children around the world, and in developing the theoretical framework needed to address decreasing this burden in a systematic fashion. T echnological advances in neuroimaging, genetics, and computational biology are providing the tools to start describing the biological processes underlying the complex course of development, and have renewed appreciation of the role of the envi-ronment in determining how a genetic heritage is expressed.
However, rapid technological change is also altering the environ-

ment of children and their families at an unprecedented rate, and what kinds of challenges to public health these changes may present is not yet fully understood. What is becoming clear is that as technological advances increase the range of available health care treatments, along with the potential cost, the choices for societies between spending limited resources on treatment or prevention will have to become increasingly deliberate.
A substantial body of work has demonstrated that prevention 
in mental health can be effective, but those who would beneﬁ  t the

in mental health can be effective, but those who would beneﬁ  t the 
most from preventive interventions are often not those with the political or economic resources to make them a priority. While the potential interventions to prevent mental health disorders in children are constrained by the knowledge and resources available, what is actually done depends upon the social and political values of individual communities and nations.
(9) It is to be hoped that as 
our understanding of these disorders grows, public policies to pre-vent the development of mental health disorders in children will become as commonplace a responsibility for modern societies as the provision of clean drinking water.
UK. National Health Service Guide for Child and Adolescent Mental Health :
http://www.bma.org.uk/ap.nsf/Content/Childadolescentmentalhealth
World Health Organization webpage for mental disorders : http://www.who.

int/topics/mental_disorders
U.S. substance abuse and mental health services administration: clinical 
preventive services in substance abuse and mental health update: from Science to services  http://www.samhsa.gov/publications/allpubs/
SMA04-3906/i.asp
Society for prevention research : http://www.preventionresearch.org
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Geneva.
 2. Costello, E.J., Egger, H., and Angold, A. (2005). 10-year research update 
review: the epidemiology of child and adolescent psychiatric disorders: 
I. Methods and public health burden. Journal of the American Academy 
of Child and Adolescent Psychiatry ,44(10), 972–86. 3. Kessler, R.C., Berglund, P ., Demler, O., et al. (2005). Lifetime prevalence

of Child and Adolescent Psychiatry ,44(10), 972–86. 3. Kessler, R.C., Berglund, P ., Demler, O., et al. (2005). Lifetime prevalence 
and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry ,62(6), 
593–602.
 4. Mrazek, P .B. and Haggerty, R.J. (1994). Institute of Medicine  (U.S.).
Committee on prevention of mental disorders, United States. Congress .
Reducing risks for mental disorders: frontiers for preventive intervention research . National Academy Press, Washington, DC.
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policy options summary report . World Health Organization, Geneva.
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practice . World Health Organization, Geneva.
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health in England . HMSO, London.
 8. WHO. (2001). Basic documents . World Health Organization, Geneva.

7. HMSO. (1992). The health of the nation: a summary of the strategy for 
 9. Detels, R. (2002). Oxford textbook of public health  (4th edn). Oxford 
University Press, Oxford, New Y ork.
10. Tulchinsky, T.H. and Varavikova, E. (2000). The new public health: an 
introduction for the 21st century , In (eds. K. Rhoshel, and 
M.D. Lenroot). Child Psychiatry Branch , National Institute of Mental 
Health, pp. 5–54. Academic Press, San Diego.
11. World Health Organization. (1993). The ICD-10 classiﬁ  cation of mental 
12. American Psychiatric Association. (2000). Task force on DSM-IV . 
Diagnostic and statistical manual of mental disorders: DSM-IV-TR(4th edn). American Psychiatric Association, Washington, DC.
13. Costello, F.J and Angold, A. (2009). Epidemiology of psychiatric disorder

13. Costello, F.J and Angold, A. (2009). Epidemiology of psychiatric disorder 
in Chilood and adolecence . In New Oxford Textbook od Psychiatry (2nd
edn.) (eds. M.G. Gelder, N.C. Andreasen, J.J. López-I bor Jr, and J.R. 
Geddes)
14. Kraemer, H.C., Stice, E., Kazdin, A., et al. (2001). How do risk factors work 
together? Mediators, moderators, and independent, overlapping, and proxy risk factors. The American Journal of Psychiatry ,158(6), 848–56.
15. Rutter, M. and Sroufe, L.A. (2000). Developmental psychopathology: 
concepts and challenges. Development and Psychopathology ,12(3), 265–96.
16. Greenberg, M.T., Domitrovich, C., and Bumbarger, B. (2001). The 
prevention of mental disorders in school-aged children: current 
state of the ﬁ  eld. Prevention & Treatment ,4(1), 1–62.
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prevention. A conceptual framework and some directions for a national 
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18. Flay, B.R., Biglan, A., Boruch, R.F., et al. (2005). Standards of evidence: 
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25. McGorry, P .D., Yung, A.R., Phillips, L.J., et al. (2002). Randomized 
subthreshold symptoms. Archives of General Psychiatry ,59(10), 921–8.9.1.4 prevention of mental disorder in childhood and other public health issues

9.2
Clinical syndromes
Contents
 9.2.1 Neuropsychiatric disorders
 9.2.2 Speciﬁ  c developmental disorders in childhood 
 9.2.3 Autism and the pervasive developmental disorders
 9.2.4 Attention deﬁ  cit and hyperkinetic disorders in childhood and adolescence
  9.2.5 Conduct disorders in childhood and adolescence
  9.2.6 Anxiety disorders in childhood and adolescence
  9.2.7 Paediatric mood disorders
  9.2.8 Obsessive–compulsive disorder and tics in children and adolescents
  9.2.9 Sleep disorders in children and adolescents
 9.2.10 Suicide and attempted suicide in children and adolescents
 9.2.11 Children’s speech and language 
difﬁ  culties
Judy Clegg

9.2.10 Suicide and attempted suicide in children and adolescents
Judy Clegg
 9.2.12 Gender identity disorder in children and adolescents
Richard GreenNote Substance abuse is considered in Part 4, Section 4.12. Aspects 
relevant to young people are considered within the chapters of this section .
9.2.1 Neuropsychiatric disorders
The developmental perspective
Developmental neuropsychiatry addresses the neurobiological basis 
of behaviour in infants, children, and adolescents with neurodevel-opmental disorders and in those with brain damage occurring during the developmental period. As a ﬁ  eld, it includes the aetiology, 
diagnosis, and treatment of behavioural, emotional, interpersonal, and psychiatric disorders.
(1, 2) The parent’s response, adjustment to, 
and involvement in treatment is a critical element in outcome.

The developmental neuropsychiatrist utilizes a developmental 
perspective that focuses on the developing person who is active, socially oriented, and emerging rather than passively responding to the environment. The adaptive plasticity of the developing nervous system to change is emphasized, and the essential role of environ-
mental experience in brain development is acknowledged. When 
working with the affected child, an effort is made to provide the supports needed to facilitate the mastery of age-appropriate devel-opmental tasks always keeping in mind the child’s individual capacities and strengths.
Scope of developmental neuropsychiatry
The scope of developmental neuropsychiatry is broad(2) and 
includes the following.
1 Neurodevelopmental disorders that are described in other chap-
ters of this book, including attention-deﬁ  cit and hyper activity

ters of this book, including attention-deﬁ  cit and hyper activity 
disorders (Chapter 9.2.4), pervasive developmental disorders and childhood-onset schizophrenia (Chapter 9.2.3), obsessive–compulsive disorder and T ourette’s syndrome (Chapter 9.2.8), and speciﬁ  c developmental disorders (Chapter 9.2.2).

1613
2 Neurogenetic disorders, both cytogenetic and metabolic, with 
behavioural phenotypes, several of which are also reviewed in Chapter 10.4.
3 T eratogenic exposure from both organic and inorganic toxins. 
In these instances, behavioural dysfunction may result from gestational substance abuse with alcohol and other substances or exposure to inorganic metals.
4 Endocrinopathies.5 Traumatic brain injury.6 Other neurological disorders (e.g. epilepsy).
Neurodevelopmental disorders
Developmental psychopathology applies developmental concepts

Developmental psychopathology applies developmental concepts 
to the study of neurodevelopmental disorders. The relationship of disordered to non-disordered behaviour is considered, as are the early origins of maladaptive behaviours that may not appear in clinical form until adolescence or adulthood. Knowledge of normal development is utilized to study children whose development is atypical, in order to understand the natural history of their disor-der and establish the developmental trajectory of that particular condition. Conversely, the investigation of such deviant behaviour associated with a particular disorder is considered in regard to our understanding of normal development. For example, attention-deﬁ cit hyperactivity disorder has been investigated as a disorder of

executive functions of the prefrontal cortex, and autistic disorder as a disorder of social cognition and communication. In both instanc-es, new knowledge about brain functions has been derived from 
these formulations. Among the neurodevelopmental disorders, the 
age of recognition varies, multiple causes are involved, and many transformations in behaviour may occur in determining their com-plex course. The goal is to understand the mechanisms and processes through which risk factors lead to the emergence of a dis-order. Disordered behaviour is not viewed as a static condition, but is considered as part of a dynamic transactional engagement. Behaviour and development are viewed within a social context, and the transactional nature of interactions is considered from infancy through adulthood to understand these processes.
Attention-deﬁ  cit hyperactivity disorder, pervasive developmental

Attention-deﬁ  cit hyperactivity disorder, pervasive developmental 
disorders, obsessive–compulsive disorder, T ourette’s syndrome, and childhood-onset schizophrenia are developmental neuropsy-chiatric disorders under active investigation and each is reviewed in the respective chapters. Their developmental psychopathology is investigated by addressing the origins and course of individual patterns of behavioural maladaptation in each of these disorders and determining their genetic bases, thought to be complex, and involving more than one gene. Information derived from genetics, developmental psychology, clinical psychology, psychiatry, sociol-ogy, physiological sciences, neurosciences, and epidemiology is included in the description of each of these disorders.
The interrelationship of the various child neuropsychiatric dis-
orders is an important consideration. Disorders may be risk factors for other conditions, so that attention-deﬁ  cit disorder may be a

orders is an important consideration. Disorders may be risk factors for other conditions, so that attention-deﬁ  cit disorder may be a 
risk factor for conduct disorder. In this instance, the child’s behav-iour affects the adult and the transactional interactions between child and adult may result in further disruptive behaviours. Moreover, there may be a developmental basis for disorders whose full presentation is not evident until later in life, as is the case with 
schizophrenia—generally considered to be a disorder of late adolescence or early adult life, but with origins in the developmen-tal period.
(3) Some disorders may have co-occurring diagnoses 
that inﬂ  uence their outcome, as in T ourette’s syndrome, where 
co-occurring conditions may determine the behavioural presentation. In T ourette’s syndrome, obsessive–compulsive symptoms may be an aspect of ‘pure’ T ourette’s syndrome, while co-occurring disrup-tive behaviour may be secondary to co-occurring attention-deﬁ  cit

disorder. Social and behavioural dysfunction in children with T ourette’s syndrome is largely ADHD-speciﬁ  c. Children with TS 
alone have a different social-emotional proﬁ  le.
(4–6) Compulsive 
behaviours may not only interfere with the normal routines for the affected child but also become particularly problematic for their impact on other family members.
Neurogenetic syndromes with behavioural phenotypes
Particular patterns of behaviour, temperament, and psychopathol-ogy may be associated with speciﬁ  c chromosomal and genetic 
(2,5,7–9)  The term ‘behavioural phenotype’ was introduced 
by Nyhan in 1972(7,10) to describe patterns of unusual behaviour 
that are so characteristic that they suggest a speciﬁ  c neurogenetic

that are so characteristic that they suggest a speciﬁ  c neurogenetic 
disorder. Nyhan described stereotypical patterns of behaviour occurring in syndromic fashion in sizeable numbers of affected individuals with a given syndrome, and observed that these patterns seemed self-programmed. In these children, he proposed that it is reasonable to hypothesize that their behaviours are associ-ated with an abnormal neuroanatomy and that such stereotypical patterns of unusual behaviour could reﬂ  ect the presence of struc-
tural deﬁ  cits in the central nervous system. Recent developments 
in the neurosciences provide a means to investigate the biological bases of behavioural phenotypes. Behavioural assessments, neuro-psychological testing, and neuroimaging procedures, carried out in well-characterized genetic syndromes, are being utilized to under-

stand pathways from genes to cognition and complex behaviours in these conditions.
Comprehensive study of children with different neurogenetic 
disorders may increase our appreciation for the relative contribu-tion of genetic variables in the pathogenesis of speciﬁ  c, affective, 
and behavioural disorders. Behavioural phenotypes have been studied most extensively in Down syndrome (language),
(11) fragile 
X syndrome (gaze aversion, hy perkinesia, autistic-lik e behaviour),(12)
Williams syndrome (sociability, hyperverbal behaviour, and 
visuospatial deﬁ  cits),(13,14)  Lesch–Nyhan syndrome (compulsive 
self-injury and aggression),(15–17)  and Prader–Willi syndrome 
(hyperphagia, obsessive–compulsive behaviour).(13,18,19) The num-
ber of identiﬁ  able behavioural phenotypes is growing with careful 
observations of behaviours in neurogenetic disorders.(8,9) Besides

observations of behaviours in neurogenetic disorders.(8,9) Besides 
behaviours, particular temperamental features have also been con-sidered in these disorders. However, when studying temperament, the appropriate measures must be chosen. For example, when Down syndrome, proposed to be linked to a particular tempera-ment, was studied using temperamental clusters of easy tempera-ment, slow to warm-up, and difﬁ  cult temperament, Gunn et al.
(20)
demonstrated both easy and difﬁ  cult temperament in children 
with Down syndrome; therefore, a typical temperamental pattern among these three categories was not demonstrated. However, when a more comprehensive assessment was carried out in other syndromes
(21) (that included the personality factors of extraversion, 9.2.1 neuropsychiatric disorders

SECTION 9  child and adolescent psychiatry 1614
agreeableness, conscientiousness, emotional stability, and openness, 
along with motor activity and irritability), speciﬁ  c personality 
phenotypes were identiﬁ  ed. These were differentially related to 
parental behaviours and family context in Prader–Willi, fragile X, and Williams syndromes. Moreover, isolated special abilities, as in calculation and in music,
(22) are recognizable that might be consid-
ered as phenotypes and linked to the proposed modular organiza-tion of the central nervous system. Finally, physical and behavioural phenotypes are not only identiﬁ  ed in neurogenetic syndromes but 
also in those caused by environmental events, such as intrauterine exposure to alcohol: namely, the foetal alcohol syndrome. Because alcoholism is a familial disorder, there may vulnerability to its effects resulting in a severe presentation in some individuals and less severe presentation in others.
(23)

(23)
Both traditional Mendelian laws of inheritance (Lesch–Nyhan 
syndrome) and non-traditional inheritance have been identiﬁ  ed in 
conditions with behavioural phenotypes. Among the non-traditionalforms of inheritance are triplet repeat amplification (fragile X syndrome), microdeletion or contiguous gene deletion (Williams syndrome), imprinting (Prader–Willi syndrome), transcriptional derepression (Rett’s syndrome), and excessive gene dosage (Down syndrome). A key ﬁ  nding is the recognition that mutations of 
single genes can lead to complex behavioural symptoms, especially if the affected protein is essential for the expression or processing of multiple ‘downstream’ genes.
Behavioural phenotypes are also discussed in relation to intel-
lectual disability in Chapter 10.5.1.
Neurobehavioural teratology

Neurobehavioural teratology investigates abnormal development of the nervous system and of cognition and complex behaviour that results from prenatal environmental insults. Neurobehavioural research addresses the prevalence of cognitive behavioural disorders in exposed individuals and the consequences of the brain insult on other developing brain systems, to identify risks for functional or behavioural deﬁ  cits. Investigators focus on cognitive behavioural 
deﬁ cits and their underlying anatomy and embryology. Assessment 
emphasizes not only IQ but also neuropsychological proﬁ  les, 
because learning disability or difﬁ  culty in visuomotor integration 
may be evident in children who function in the low to average range of general mental ability.
The natural history of intrauterine drug exposure on motor,

The natural history of intrauterine drug exposure on motor, 
cognitive, emotional, and social behaviour is an area of growing 
 concern. Multiple drug exposures during pregnancy are common 
among substance-abusing mothers. Of syndromes associated with intrauterine substance abuse, alcohol abuse has been studied the most extensively. Subsequently, retinoids, anticonvulsants (lithium, tegre-tol, and valproic acid), and the selective serotonin-reuptake inhibitors have also been studied. Other teratogens do not lead to major malfor-mations of the nervous systems but they do compromise its integrity (for example, lead, heroin, methadone), and are associated with neu-rotoxic damage or effects on neurochemical systems.
The greatest period of vulnerability to drugs in a human preg-

nancy is during the period of embryogenesis (days 14 to 60). During embryogenesis, many neurobehavioural teratogens (for instance, retinoids and ethanol) produce syndromes with abnor-malities that involve craniofacial, neural, and major organ systems. Behavioural abnormalities without detectable physical abnormality can occur when the insult occurs during the foetal period. The extent of malformation is stage-speciﬁ  c and dose-dependent, 
with outcomes ranging from death with malformation, malforma-
tion and survival, effects on growth, and cognitive–neuropsycho-logical or behaviour disorder. The same exposure to alcohol needed to produce cognitive behavioural change in the foetal period would generally cause malformation if it occurred during embryogenesis. The term ‘developmental toxicology’ is sometimes used if the insult 
occurs in the postnatal period.
There may be a genetic vulnerability that inﬂ  uences the extent

There may be a genetic vulnerability that inﬂ  uences the extent 
of expression of response to environmental toxins in an individual. A common family of regulatory genes is involved in the formation of structures of the face, head, hindbrain, parts of the heart, and thymus gland, all of which share a common origin from neural crest cells (anterior neural tube). These regulatory genes, known as HOX genes, provide rules for assembling various structures and for determining particular anatomical segments.
(24) Homozygous 
HOXA1 mutations have been shown to disrupt human brainstem, inner ear, cardiovascular and cognitive development. Because the retinoid family is involved in controlling these HOX genes,
(25) a 
similar pattern is produced by excessive retinoid administration, as in hype rvitaminosis of vitamin A (retinol). Moreover, the enzyme

(25) a 
similar pattern is produced by excessive retinoid administration, as in hype rvitaminosis of vitamin A (retinol). Moreover, the enzyme 
alcohol dehydrogenase functions in the metabolism of both retinol and ethanol so that intoxicating levels of ethanol can competitively inhibit the metabolism of retinol and impact brain development. Thus, both genetic and teratogenetic agents may produce similar developmental abnormalities. Understanding these mechanisms helps to understand how an abnormal facial appearance may suggest an abnormal brain.
Foetal alcohol spectrum disorder syndrome
Foetal alcohol syndrome is one of the most commonly recognized causes of intellectual disability; one that is preventable if recommended guidelines regarding alcohol use are followed by mothers.
(26)
Children with the full foetal alcohol syndrome demonstrate prenatal and postnatal growth deﬁ  ciency, microcephaly, infantile

(26)
Children with the full foetal alcohol syndrome demonstrate prenatal and postnatal growth deﬁ  ciency, microcephaly, infantile 
irritability, mild to moderate intellectual disability, and a character-istic facial appearance.
(23) The extent of the abnormality depends 
on the time of maximal exposure to alcohol and the dose. Approximately half of those affected have co-ordination problems, are hypotonic, and have attention deﬁ  cits. Between 20 and 50 per cent 
have other birth defects, including eye and ear anomalies and cardiac anomalies. Those children who do not show growth retar-dation or congenital anomalies may show more subtle changes, such as attention problems, disruptive behaviour, reduced speed of information processing, motor clumsiness, speech disorders, ﬁ  ne 
motor impairment, and learning problems, especially in mathe-matics.
(23,27)  These ﬁ  ndings have been documented in a prospec-

tive longitudinal study of the effects of prenatal alcohol exposure on a birth cohort of 500 offspring who were selected from 1529 consecutive pregnant women in prenatal care in community hospitals.
(28) Dose-dependent effects are most clear from the neu-
robehavioural status of subjects when regular neurodevelopmental evaluations are carried out from birth to age 14 years. The more subtle abnormalities are referred to as ‘foetal alcohol effects’ , or alcohol-related neurodevelopmental disorder. The full range of disabilities is described as foetal alcohol spectrum disorder.
(27)

1615
Subjects with average to above-average IQ may demonstrate 
neuropsychological deﬁ  cits in complex attention, verbal learn-
ing, and executive functioning. Disruptive behaviour, attention-deﬁ cit disorder, anxiety disorder, and communication disorder 
have been described
(29,31,33) in children with foetal alcohol syn-
drome and foetal alcohol spectrum disorder who test in the low normal range and in the moderate to severe range of intellectual disability.
Behavioural phenotype
The behavioural phenotype is characterized by problems in cogni-tive functioning, academic problems in arithmetic, difﬁ  culty with 
abstractions, understanding cause and effect, and generalizing from one situation to another. Thus, inattention, poor concentration, impaired judgement, memory deﬁ  cits, and problems in abstract 
reasoning are characteristic. Behavioural problems related to impulsivity and hyperactivity makes them vulnerable to later diag-noses of oppositional deﬁ  ant and conduct disorder.

(27,30)
Foetal alcohol spectrum disorder is not only a childhood disorder; 
the cognitive and behavioural effects and psychosocial problems may persist throughout adolescence into adulthood.
(28,33)  Although 
the facial features are not as distinctive after puberty and the growth deﬁ ciency is not as apparent as in the younger child, the central 
nervous system effects do persist throughout life. Approximately 50 per cent of those affected function as intellectually disabled persons. Moreover, adaptive behavioural problems in communica-tion skills and in socialization are apparent in those with foetal alcohol spectrum disorder whose intelligence test scores are in the normal range.
Poor judgement, attention problems, distractibility, difﬁ  culty in

Poor judgement, attention problems, distractibility, difﬁ  culty in 
recognizing common social cues, and problems in modulating mood continue as characteristic features. Family environmental 
problems often continue as risk factors for behavioural problems if there is a lack of stability in family life. In one follow-up study
(34)
that used structured interviews with non-intellectually disabled affected subjects, the most common diagnoses were alcohol or drug dependence, mood disorders, and personality disorders (especially passive aggressive or antisocial). Further follow-up is needed to investigate the mechanisms involved in these psychiatric presenta-
tions, and particularly in determining the pathways leading to 
alcoholism.

Foetal alcohol syndrome is a common cause of neuropsychiatric disorders, with a worldwide incidence of approximately 1.9 in 1000 live births. When foetal alcohol syndrome and alcohol-related neurodevelopmental disorder are considered together, the combined rate in one study conducted in the United States was 9.1 in 1000.
(35) Despite its frequency and severity, the syndrome may 
go unrecognized because physicians may not systematically enquire about alcohol use and may not recognize the spectrum of the effects of prenatal alcohol exposure on neurodevelopment.
Aetiology
The amount and pattern of alcohol consumption and the trimester of use during pregnancy, especially if during critical periods of brain development, are major factors in determining outcome. Binge drinking patterns with high blood concentrations are espe-

cially deleterious. Rapid changes in alcohol concentrations in the blood and central nervous system cause apoptotic damage (cell degeneration) in developing neurons and other cells in rat mod-els.
(36) Microcephaly is commonly reported in foetal alcohol syn-
drome and suggests an underdevelopment of the brain. Neuropathological studies demonstrate the underdevelopment or absence of the corpus callosum and enlarged lateral ventricles. Dendritic changes have been observed in animals with prenatal exposure to alcohol; these changes were correlated with decreased learning ability. Magnetic resonance imaging studies have docu-mented brain abnormalities in foetal alcohol syndrome, particu-larly in midline frontal structures such as the corpus collosum.
(37,38)
Research to identify speciﬁ  c polymorphisms contributing to foetal

(37,38)
Research to identify speciﬁ  c polymorphisms contributing to foetal 
alcohol spectrum disorder is at an early stage. Polymorphisms of only one of the genes for the alcohol dehydrogenase enzyme family, the ADH1B, have been demonstrated to contribute to 
vulnerability.
(39)
Treatment
(a) Evidence
Mothers of children with foetal alcohol syndrome who drank more alcohol and drank excessively early in gestation have more severe clinical features. Alcohol use in late pregnancy is primarily associated with prematurity and infants who are small for gestational age, rather than with the full foetal alcohol syndrome. Because of these risks, treatment must begin with prevention.
(32) There is no clearly

(32) There is no clearly 
agreed safe dose of alcohol for pregnant women. Because there is no known safe amount of alcohol consumption during pregnancy, it is recommended that women who are pregnant or who are planning a pregnancy abstain from drinking alcohol. Special efforts for educating women of child-bearing age are required that high-
light the harmful effects of alcohol; identiﬁ  ed children must be 
referred for early educational services.
A comprehensive treatment programme begins with parental 
acknowledgement of the aetiology of foetal alcohol syndrome or spectrum disorder and treatment for the parent, as indicated, for alcohol misuse and abuse. Parental counselling should include discussion of the physical and behavioural phenotype. The family should be advised about the need for special educational pro-grammes and assisted in behavioural management. Family therapy is often required to help family members cope with the developme ntal

disorder. Appropriate educational and behavioural treatment resources are needed to address the social deﬁ  cits, particularly in 
those cases where disruptive behaviour, attention-deﬁ  cit disorder 
and mood disorders are identiﬁ  ed.
Foetal alcohol syndrome is also considered as a cause of intellec-
tual disability in Chapter 10.4.
Gestational substance abuse
Opiates
Exposure to heroin and methadone ranges from a neonatal with-drawal syndrome to less predictable long-term outcomes.
(40) An 
impoverished environment may have disproportionate adverse effects on methadone-exposed children when compared to unex-posed children.
(41) Methadone effects have been associated with 9.2.1 neuropsychiatric disorders

SECTION 9  child and adolescent psychiatry 1616
increased body tension, poor motor co-ordination, and delay in 
motor skills acquisition.(42) However, the effects on mental 
development are less clear, but they do affect the child-rearing environment. Since methadone exposure produces an increased vulnerability to the effects of poor parent–infant relationships, these relationships require careful monitoring.
Cocaine
Cocaine is a central nervous system stimulant that inhibits nerve conduction in the peripheral nervous system. Cocaine is metabolized primarily through the plasma cholinesterase system, with the primary metabolic product being benzoylecgonine. Since cocaine rapidly crosses the placenta by simple diffusion, foetal peak blood levels are reached as quickly as 3 min.
(43) Having crossed the

(43) Having crossed the 
placenta in the foetus, cocaine has the same direct actions on the foetal cardiovascular system as seen in the maternal system. These cardiac changes involve the direct effects of cocaine, as well as indi-rect effects such as foetal hypoxia. Cocaine may lead to placental dysfunction (via vasocontracture effects), structural changes (via vascular compromise), and neurobehavioural abnormalities (via postsynaptic junction neurotoxicity).
Infant gestational age, birth weight, head circumference, and 
length have been found to be decreased in affected infants, and low birth weight is a frequent ﬁ  nding in studies of the offspring of

length have been found to be decreased in affected infants, and low birth weight is a frequent ﬁ  nding in studies of the offspring of 
cocaine-using women. In addition to abnormal growth patterns, congenital anomalies involving the genitourinary tract, heart, and central nervous system as well as limb-reduction abnormalities have been reported. A potential mechanism for all these anoma-lies appears to be interruption of the intrauterine blood supply, with subsequent disruption of embryonic development. Although approximately 25 to 30 per cent of infants exposed to cocaine in 
utero  may have physical difﬁ  culties, overall neurobehavioural 
problems may be more common, and most apparent in early infancy and childhood.
(40, 44) In one large study, at age 4 years,

(40, 44) In one large study, at age 4 years, 
prenatal cocaine exposure was not associated with lower full-scale, verbal, or performance IQ scores but was associated with an increased risk for speciﬁ  c cognitive impairments. A better home 
environment was associated with IQ scores for cocaine-exposed children that are similar to scores in non-exposed children. Although irritability and problems in state regulation are report-ed in infants and impulsive behaviour in pre-school children, these behaviours diminish over time with behavioural and psy-chosocial interventions.
(45) Child abuse is closely linked to sub-
stance abuse.
Treatment
These ﬁ  ndings suggest that careful attention be paid to the post-
natal home-rearing environment of children who are exposed to drugs in utero . Overall, the treatment programme must take into

natal home-rearing environment of children who are exposed to drugs in utero . Overall, the treatment programme must take into 
account physical and psychological change secondary to intra-uterine drug use as well as the postnatal nurturing environment. Both substance use and psychiatric disorder in the parents must 
be considered, because parents with attention-deﬁ  cit disorder and 
mood disorders may themselves self-medicate with cocaine. Without early intervention, special school programmes, behav-ioural management programmes, and a structured day pro-gramme will be necessary. Ongoing parent training is also required.
(40, 42)Endocrinopathies
Congenital hypothyroidism
Congenital hypothyroidism is associated with intellectual disablity and may be associated with decreased motor activity at birth, hoarse cry, and difﬁ  culty with feeding. It is rarely diagnosed at birth

from clinical assessment alone, but it is recognized from newborn screening tests with confirmation by measurement in blood samples. Symptoms of hypothyroidism may not be clearly detected until the second month of life. The overall prevalence is 1 in 4000 live births. Neurological and learning disorders associated with untreated congenital hypothyroidism include attention-deﬁ  cits, 
hearing loss, speech defects, ataxia, and abnormal muscle tone.
(46)
Rapid diagnosis in infancy is essential to prevent these complica-tions. Without treatment, severe neurological dysfunction ensues. With initiation of oral thyroid hormone treatment (levothyroxine in a single daily dose of 8 to 10 μg/kg per day) in the ﬁ  rst 6 weeks

of life, IQ is in the normal range. If treatment is delayed until 3 to 6 months, IQ drops to an average of 75, and, if initiated after 6 weeks, to an IQ of 55 or less. Rearing environment is important in long-term outcome. Despite early treatment there still may be enduring cognitive and motor deﬁ  cits in young adults.
(47)
Traumatic brain injury
Traumatic brain injury is deﬁ  ned as physical damage or impairment 
in function of the brain as a consequence of the application of acute mechanical force. Other causes of brain injury result from birth trauma, poisoning, or asphyxia. Traumatic brain injury is a major cause of death and disability among children, adolescents, and young adults, and is one of the most common causes of chronic brain syndromes in childhood. Traumatic head injury is common and becoming increasingly more so.
(a) Cognitive and behavioural

The most common long-term outcomes of traumatic brain injury are cognitive and behavioural changes. Immediately after emerging from a coma, the child will be unable to form new memories. The time, from the accident to the time when new memories emerge, is referred to as post-traumatic amnesia. The length of coma and the duration of post-traumatic amnesia are especially important in regard to the extent of cognitive recovery. Moreover, there is a strong inverse relationship between subsequent IQ and duration of coma. The persistence of cognitive deﬁ  cits is correlated 
with the duration of post-traumatic amnesia; the more persistent deﬁ cits follow more than 3 weeks of post-traumatic amnesia. 
Persistent verbal memory impairment is reported as long as 10 years after injury in up to one-quarter of those studied. Psychiatric symptoms in adults occurs more often following focal frontal-lobe

Persistent verbal memory impairment is reported as long as 10 years after injury in up to one-quarter of those studied. Psychiatric symptoms in adults occurs more often following focal frontal-lobe 
traumatic br ain injury than injury to other cerebral areas. In children, 
Rutter
(48,49) reported behavioural disinhibition after severe closed 
traumatic brain injury characterized by over-talkativeness, ignoring social conventions, impulsiveness, and poor personal hygiene.
(b) Psychiatric
Psychiatric outcomes can be divided into those that occur during the early phases of recovery and those that occur later. The earliest

1617
psychiatric sequelae are found before the termination of post-
traumatic amnesia. During this time, behavioural and affective 
symptoms are linked to the neurological presentation. The most common psychiatric diagnosis is delirium. Symptoms include short attention span, agitation, hallucinations, and disturbances in the sleep–wake cycle.
Subsequent occurrence of post-traumatic psychiatric symptoms 
is linked to the severity of the injury, its location, the child’s behavioural and emotional features prior to the accident, and the psychosocial interactions of the family members during the recov-ery phases. The more severe the traumatic brain injury, the greater the likelihood of psychiatric sequelae. All children in one prospec-tive study of severely injured children who had premorbid psychi-atric conditions showed post-traumatic psychiatric disorders.
(50,51)

(50,51)
Moreover, over half the children in this group who had no premor-bid symptoms prior to the accident had developed psychiatric symptoms during a 28-month, follow-up period. The greatest pre-morbid risks for psychiatric disorder were previous difﬁ  culties with 
impulse control and disruptive behaviour. In addition, a prior history of family dysfunction increased the risk for later symptom-atology. The range of disorders includes attention-deﬁ  cit hyperac-
tivity disorder,
(52) disruptive behaviour(53) post-traumatic mood 
disorders (both depressive and manic symptoms), post-traumatic stress disorder,
(54) and family dysfunction.(55,  56)  Transient psychotic 
features may occur. Hallucinations tend to be less bizarre and more concrete than the typical hallucination in schizophrenia. Moreover, head injury in childhood may accelerate the expression of schizo-phrenia in families where there is strong genetic predisposition
(57)

(57)
Injuries involving focal frontal-lobe dysfunction are associated with impulsive aggression and behavioural dyscontrol,
(58) most 
often following focal orbitofrontal injury. The rate of actual aggres-sion is less than often assumed. When forensic issues are consid-ered regarding violent behaviour each case should be evaluated individually taking into account the type of head injury and other risk factors especially a history of physical abuse.
Classiﬁ  cation—types of traumatic brain injury
Neurological damage associated with head trauma can be produced 
in several ways. Traumatic brain injury is classiﬁ  ed as open or closed;

in several ways. Traumatic brain injury is classiﬁ  ed as open or closed; 
these types differ in the pattern of injury and neurobehavioural outcome. Open refers to penetration of the skull, as in a depressed skull fracture or bullet wound, the extent depending on the regions damaged by contusion or cerebral oedema. Closed head injury results from acceleration and deceleration of the brain within the hard skull; this often leads to contusion of the brain from a sudden impact and may result in subarachnoid haemorrhage. Different parts of the brain have different densities, and therefore shearing stresses that develop during rapid brain movement cause injury. Furthermore, compression of blood vessels against the falx cerebri or tentorium may result in infarction of the areas, which these blood vessels supply. Penetrating traumatic brain injury causes

speciﬁ  c and direct loss of neural tissue.
It is estimated that 185 children per 100 000 from infancy to 14 years 
of age and 295 per 100 000 adolescents and young adults aged between 15 and 24 are hospitalized each year for traumatic brain injury.
(59) The risk is highest among the 15- to 19-year-olds where the rate is 550 per 100 000.(60) The incidence in paediatric popula-
tions is similar to that in adults. In the United Kingdom the rates 
for those under 16 years is approximately 45 000, with about 300 deaths each year.
(61) A mortality rate of 10 per 100 000 makes 
head trauma a major cause of death in children, but the death rate is still less than that in adults. There is no difference in the death rate between boys and girls before the age of 5 years, but after this age males are four times more likely to die than females. Approximately 90 per cent of head injuries are mild.
(61) Falls and 
transport injuries make-up the majority of cases. Inﬂ  icted traumatic

transport injuries make-up the majority of cases. Inﬂ  icted traumatic 
brain injury from physical abuse is a growing concern especially of repeated injuries. A US statewide population based study found the incidence of inﬂ  icted traumatic brain injury to be 17 per 100 000 
person-years in the ﬁ  rst 2 years of life with the highest incidence in 
infants during their ﬁ  rst year (30/100 00). The rate was higher in 
boys than girls.
(62)
Aetiology

(62)
Aetiology
The causes of traumatic brain injury are different depending on the age of the child. The incidence is twice as high in males as in females, and children who live in poor psychosocial circumstances are at greater risk. Traumatic brain injury from child abuse occurs in infancy: in the pre-school years the most common cause is falls; in early elementary school, it is pedestrian accidents. From 10 to 14 years of age there is an increase in sports and bicycle accidents, but by 15 years motor vehicle accidents and violent assault are the most common. Risk factors include poverty, single-parent homes, congested living arrangements, and a parental history of psychiatry disorder.
A common complication of traumatic brain injury is cerebral

A common complication of traumatic brain injury is cerebral 
oedema, but there are other complications such as infection and haematoma formation both inside and outside the brain. These complications result in neurological deﬁ  cits that may be extensive. 
Furthermore, compensatory mechanisms that are involved in recovery from head trauma may alter brain function. A child who has suffered a traumatic brain injury is likely to experience both neurological and psychiatric difﬁ  culties depending on the brain 
regions involved. Multiple mechanisms lead to psychological symp-tom formation—both psychosocial and physiological factors are involved.
The level of consciousness, degree of somatic injury, extent and duration of post-traumatic amnesia, severity of head injury, and degree of neurocognitive dysfunction in the early post-trauma period 
are important in determining outcome. Children who experience severe traumatic brain injury usually follow a predictable postop-

erative course.
(48) As previously noted, landmarks for recovery are 
associated with the time of emergence from coma and the time of emergence from post-traumatic amnesia. The emergence from coma is most often deﬁ  ned as the point at which the patient is able 
to follow simple verbal commands. Concurrently, visual tracking of objects in the environment may be observed.
Post-traumatic amnesia ends when the child is able to form new 
memories. The frequency of post-traumatic amnesia is probably related to concurrent injury to the temporal lobes associated with the head trauma. However, older memories may be recalled that do not involve the temporal lobe. The hippocampus has a central role 9.2.1 neuropsychiatric disorders

SECTION 9  child and adolescent psychiatry 1618
in the formation of new memories. Besides recovery from post-
traumatic amnesia, another form of memory loss-retrograde 
amnesia-for events that took place before the accident, typically becomes shorter and shorter during the recovery process. It is important to remember that children with severe head trauma will rarely have speciﬁ  c memories of the accident itself. Overall, the 
most important milestones in recovery for future outcome are the length of coma and the duration of post-traumatic amnesia.
Treatment
Most mild head injury and post concussive problems will resolve without treatment. When there are ongoing symptoms, parents and teachers must adjust expectations depending on the extent of injury. Complete recovery of all brain functions following severe brain injury is rarely accomplished. Still, if recovery is deﬁ  ned as a

reduction in impairments in behavioural and physiological func-tions over time then changes do occur so that, typically, there is recovery of function together with a fair amount of substitution of function. Mechanisms include resolution of brain swelling (oede ma), 
resolution of damage to other brain regions damaged through shock (diaschisis), changes in the structure of the nervous system (plasticity), and regrowth of neural tissue (regeneration). The extent of recovery depends on the severity of the injury, the number of times injured, the age at the time of injury, premorbid cognitive 
status, extent to which loss functions can be subsumed under other 
systems, integrity of other parts of the brain, individual brain structures, motivation, emotional considerations, and the quality of rehabilitation programme.
(63, 64)
Although children and adolescents tend to have a better outcome

(63, 64)
Although children and adolescents tend to have a better outcome 
after severe traumatic brain injury than those over the age of 21, the adult brain has greater plasticity than previously considered. Despite this general rule, children who are younger than 7 years may have a worse outcome since they may be at increased risk of child abuse as a cause of injury which may be particularly trau-matic. Furthermore, younger children may have a worse outcome based on the global effects of trauma on the developing brain. The duration of recovery of signiﬁ  cant neuropsychological, behav-
ioural, and emotional deﬁ  cits may last several years following injury. 
These higher cognitive deﬁ  cits lead to the major disability observed 
with traumatic brain injury.

Partial recovery of function can and does occur over time, not only in children but also in adults. Intervention through retraining and the use of cognitive memory aids is targeted to improve areas of cognitive functioning such as memory, attention, language, and perception.
(63) Even though partial recovery does occur after 
various types of brain injury, there is variability in the extent of recovery.

The most important primary injury prevention activities focus on teaching safe behaviour, the use of seat belts in cars, and wearing helmets when riding horses, bicycles, or motorcycles. Once an injury has occurred both anticipatory guidance, which teaches the family and child what to expect, and preventive intervention strategies are necessary. Early and focused rehabilitation proce-dures coupled with medication for associated psychiatric disorder, behaviour management, supportive therapy for families, and 
appropriate school programmes are necessary to prevent behav-ioural and psychiatric complications.
Epilepsy

Epilepsy
Epilepsy refers to recurrent seizures that are idiopathic (of unknown aetiology) or due to congenital or acquired brain lesions. Epilepsy is the symptomatic expression of brain pathology or dis-ordered brain function and is not a disease in itself. The symptom complex is episodic and associated with an excessive self-limiting neuronal discharge. The seizure is a frightening experience for parents and they require support and guidance. Epilepsy impacts the whole family and can create problems for all family members.
(65)
Clinical features and clinical course
Complex partial seizures involving the temporal and frontal lobe is the most common condition where complex neurological and psychiatric symptoms are seen in the same person. Complex symp-toms include behavioural automatisms, perceptual alterations, changes in affect and memory, distorted thinking, and hallucina-tions

(66) Forms occurring in infancy and childhood include 
temporal lobe epilepsy, frontal-lobe epilepsy, infantile spasms, Lennox–Gastaut syndrome, Landau–Kleffner syndrome, and benign focal epilepsy.
(67)
Children with partial seizures and electroencephalographic 
evidence of frontal involvement have more severe formal thought disorders and deﬁ  cits in communication discourse than those with 
temporal involvement. Because these seizures are rare in children, reports of symptoms are primarily found in case reports. For exam-ple, Saygi et al.
(68) and Stores et al.(69) have described sexual disinhi-
bition, pressured and tangential speech, screaming, aggression, disorganized behaviour, and nightmares in affected children.
Frontal-lobe epilepsy should be considered if there are episodes

Frontal-lobe epilepsy should be considered if there are episodes 
of brief sudden unresponsiveness without loss of consciousness. These episodes occur with continued understanding of spoken language and clonic or tonic motor phenomena involving the face and arms bilaterally. Laughing, crying, pedalling movements, and sexual automatisms may also suggest this diagnosis. A normal elec-troencephalograph does not rule out the diagnosis. Left frontal hypometabolism on positron-emission tomography scanning or reduced cerebral blood ﬂ  ow to the frontal area, although not diag-
nostic, support this diagnosis.
The Lennox–Gastaut syndrome is characterized by early onset 
of intractable seizures and bilateral slow spike-wave complexes on the EEG.
(70) The onset is typically between the ages of 1 and 7 years.

(70) The onset is typically between the ages of 1 and 7 years. 
The seizure pattern includes tonic, generalized toni c–clonic, atypical 
absence, atonic, and myoclonic seizures. Approximately half of children with the Lennox–Gastaut syndrome test as intellectually disabled. Marked language delay, overactivity, and irritability are characteristic. However, these behavioural symptoms may improve with seizure control. Ultimately, the diagnosis is based on the characteristic EEG ﬁ  nding of interictal slow spike-wave discharges 
in children with the early onset of poorly controlled seizures and a developmental disorder. In some instances, there is prolonged minor status epilepticus. Such episodes may last for several weeks during which the child engages in a variety of everyday activities but is socially unresponsive, aggressive, less articulate, and has

1619
minor twitching of the face and hands. This presentation must be 
differentiated from a psychiatric disorder.
Classiﬁ  cation of epileptic seizures utilizes both clinical and electro-
encephalographic features.(71) The current classiﬁ  cation divides 
seizures into two categories: partial and generalized. Partial seizures involve one cerebral hemisphere, in part or totally. They begin focally, although they may become generalized. Consciousness is preserved but cognitive functions may be transiently impaired: for example, speech may be impaired if the dominant hemisphere is affected. Partial seizures are further subdivided into those with simple or complex symptomatology. In children, simple com-plex seizures are most often simple motor or sensory phenomena. Complex partial seizures usually begin in temporal or frontal-lobe structures. It is this group that is particularly important to psychiatrists.

Epilepsy is a clinical rather than a laboratory diagnosis, and diag-nostic errors most commonly occur due to inadequate history and physical examination. The accuracy of diagnosis has improved with the establishment of a universally agreed upon classiﬁ  cation. 
In some instances there may be confusion between sleep arousal disorders and epilepsy.
(72)
The differential diagnosis includes complex partial seizures of

(72)
The differential diagnosis includes complex partial seizures of 
temporal lobe origin and pseudoseizures. Frontal-lobe complex partial seizures differ from those of temporal lobe origin in that the amnesia of frontal-lobe seizures is more pronounced than the extent of loss of consciousness. Moreover, frontal-lobe involvement is associated with unilateral or bilateral tonic posturing and pedal-ling movements, partial and not complete loss of consciousness, and eye and head deviation to the contralateral side. In complex partial seizures of temporal lobe origin, oroalimentary and repeti-tive hand automatisms, and looking around are characteristic. Lastly, sensory, gustatory, or olfactory hallucinations in frontal-lobe epilepsy must be differentiated from psychotic disorders such as schizophrenia and manic psychosis.
The distinction between true seizures and pseudoseizures can be

The distinction between true seizures and pseudoseizures can be 
difﬁ cult. Children with pseudoseizures commonly also have true sei-
zures. Emotional dysphoria can precipitate true seizures and many children with chronic seizures have psychiatric diagnoses. Frontal-lobe seizures may be confused with pseudoseizures. Frontal complex partial seizures differ from pseudoseizures in that pseudoseizures have a gradual onset and longer duration, while frontal-lobe seizures start slowly and last less than 1 min. Pseudoseizures include thrusting or rolling movements rather than the rhythmic ﬂ  exion and extension 
clonic movements seen in frontal-lobe epilepsy. Still, it may be difﬁ  -
cult to distinguish pseudoseizures
(73) and video and electroencepha-
lograph monitoring with depth electrodes may be necessary to deﬁ  n-
itively diagnose frontal-lobe epilepsy.
Other features differentiating pseudoseizures are as follows:
1 The seizure occurs when the child is observed, but not when 
alone.

alone.
2 The seizures are gradual rather than of sudden onset.3 Uncontrolled flailing occurs, rather than true tonic–clonic 
movements.4 The seizure is accompanied by histrionics, with screaming and 
shouting.
5 Painful stimuli are avoided during an attack;6 There is a sudden cessation of the seizure, with immediate return 
to an alert and responsive state.
7 There is absence of paroxysmal discharge during an attack on 
electroencephalography.
(73)
The incidence of epilepsy ranges from 0.7 to 1.1 per cent of the general population. It is the most common of the neurological diseases diagnosed in children.
(67) Approximately 50 per cent of

(67) Approximately 50 per cent of 
all cases of epilepsy begin during the childhood years and about 5 per cent of children will experience repeated epileptic seizures without a known extracerebral cause. In addition, about 3 per cent of children will have febrile convulsions that are usually benign and accompany a febrile illness. The great majority of these children, approximately 98 per cent, do not go on to develop true epilepsy. Other causes include hypoglycaemic seizures in children with dia-betes. In some instances, as in tuberous sclerosis complex, cognitive impairment and autistic regression with onset in the ﬁ  rst year of 
life, are linked to epilepsy; and in others there is a late onset of language disorder as in the Laudau–Kleffner syndrome.
The British Child and Adolescent Mental Health Survey
(74)

(74)
canvassed over 10 000 children and adolescents and identiﬁ  ed 
0.7 per cent of 5–15 year olds with a diagnosis of epilepsy. Among them there was an increased prevalence of emotional, behavioural, and relationship problems within families and among peers.
Aetiology
Advances in understanding epilepsy in childhood have come from 
the newer medical technologies. Recognition of a typical spike-wave 
pattern has led to the identiﬁ  cation of benign focal epilepsy. CT 
scanning and high-resolution magnetic resonance imaging ( MRI )

have led to the recognition of mesial temporal sclerosis, tuberous sclerosis, neuroblast migrational disorders, and small temporal lobe tumours. Positron-emission tomography scanning can demonstrate lesions undetected by MRI, such as focal lesions in patients with hypsarrthymia. Advances in surgical procedures have decreased the risks associated with callosotomies and hemispherectomies used for catastrophic seizures. New under-standing about neurotransmitters involved in the production and inhibition of seizures has led to advances in seizure medications.
Epileptic seizures are the result of an imbalance between inhibi-
tory [( γ-aminobutyric acid ( GABA ) and excitatory (glutamate)] 
neurotransmitter systems. Neuronal hyperexcitability leading to seizures may result from decreased inhibition or increased excitation.

(75) Epilepsy has its highest incidence in childhood, sug-
gesting that the immature brain is more vulnerable to seizures than the mature brain—a ﬁ  nding that is borne out by animal studies. 
Decreased inhibition or increased excitation may result in neuro-nal excitability and seizures.
(75) The speciﬁ  c mechanisms responsi-
ble for this imbalance remain uncertain. However, it is known that the binding of GABA to GABA
A receptors opens a chloride channel 
(ionophore) leading to a ﬂ  ux of chloride ions and consequent 
membrane hyperpolarization: it is also known that there are fewer GABA
A high-afﬁ  nity receptors in immature animals. Similarly, 
there are maturational differences in the development of major 9.2.1 neuropsychiatric disorders

SECTION 9  child and adolescent psychiatry 1620
ionotrophic receptors in excitatory systems and in the activation of 
N-methyl-d-aspartate receptors. In younger animals this results in 
larger excitatory postsynaptic potentials. It remains a puzzle why certain seizure types are age-speciﬁ  c in their onset.
(76)
Epilepsy syndromes may have a genetic basis.(77) Gene localiza-
tion for ﬁ  ve epilepsy syndromes with Mendelian inheritance are 
recognized, and localization has been suggested in three epilepsies with complex inheritance. Those epilepsies with a single gene inheritance include symptomatic epilepsies with associated diffuse brain dysfunction and idiopathic epilepsies, where the seizures are the primary brain abnormality. Idiopathic single gene epilepsies include benign, familial neonatal convulsions. T o date four autoso mal-

dominant forms of epilepsy have been described. Most genes dis-covered to be involved in human epilepsies encode subunits of ion channels, both voltage-gated and ligand-gated.
(77) Molecular 
genetic studies are expected to lead to the discovery of other epilepsygenes. Investigation of animal models of epilepsy is continuing.
The aetiology of temporal lobe seizures includes mesial temporal 
sclerosis, tumours, and cortical dysplasia. The younger the child, the less frequent is mesial temporal sclerosis. Other factors linked to aetiology are proposed: temporal lobe hypoperfusion and hypo-metabolism in Landau–Kleffner syndrome, and diffuse cortical and subcortical hypoperfusion in Lennox–Gastaut syndrome.

Early-onset epilepsies are associated with cognitive, behavioural, and communication disorders. Moreover, there is evidence that both clinical and subclinical epilepsy may result in developmental deviance, which has led to earlier and more aggressive treatment to try to prevent these impairments. Psychosocial factors are impor-tant in impairment. One prospective study evaluated 220 adults with childhood-onset seizures
(78) up to age 35. The majority of 
subjects were free of seizures as adults, but were at risk for social and educational problems. When compared with random control subjects, those with epilepsy demonstrated correlations between neurological and cognitive impairment and social deﬁ  cits. Those

with epilepsy only (100 subjects) had a fourfold risk of psychiatric disorder. The authors reported social adjustment problems, competence problems, and reduction in marriage rate and fertility. Psychotic disorders occur signiﬁ  cantly more frequently in people 
with epilepsy than in the general population with prevalence rates ranging from 2 to 8 per cent; the prevalence varying with the type of seizure disorder.
(79)
Cognitive and behavioural ﬁ  ndings suggest the importance of early

(79)
Cognitive and behavioural ﬁ  ndings suggest the importance of early 
intervention to prevent negative outcomes. The behavioural and psychiatric problems should be treated with the same approach used in children who are neurologically intact and include educa-tional, family, and pharmacological approaches. The indications and choice of psychiatric drugs is similar; epilepsy is not a strong contraindication for the use of neuroleptic or antidepressants, even though some of these medications may increase the frequency of seizures. Dexedrine may be the treatment of choice for hyperkinetic behaviour because it may increase the seizure threshold. Although caution is needed in those with more severe neurological involve-ment, there is no strong evidence for an increased risk for neuro-leptic-induced tardive dyskinesia. When there are behavioural problems one must consider the behavioural effects associated with anticonvulsant medications.
(80) In some instances, reducing the

(80) In some instances, reducing the 
dose or changing the medication may be helpful and this should 
be discussed with the referring physician.
The major drugs used for treatment include carbamazepine, 
valproic acid, gabapentin, vigabatrin, and topiramate. These medi-
cations are used for the various forms of epilepsy described above including temporal lobe seizures and Lennox–Gastaut syndrome. Lamotrigine is also used, but with caution because severe dermato-logical side-effects may occur. In some instances, temporal lobec-tomy has been successful in the control of behavioural dysfunction and illogical thinking when performed in children with intractable temporal lobe seizures. In tuberous sclerosis complex the seizure medication vigabatrin may be helpful (and more so than cortico-steroids) for infantile spasms.
(81)

(81)
A developmental perspective is indicated as there is increasing evidence of there being a developmental period during which a structure or function can be developed most completely.
(82) For 
example, in tuberous sclerosis complex the cognitive impairment and autistic regression may be approached by way of early drug therapy and, in some instances, by the surgical removal of tubers.
(83)

(83)
Thus a developmental understanding of epilepsy is now crucial in treatment planning. Research is continuing to clarify why, in some instances, epilepsy may have a severe developmental impact and in other instances be more benign. With greater understanding of genetic mechanisms appropriate family counselling will be needed, and perhaps, new drug treatments may emerge. An important treatment goal is to prevent adverse psychosocial outcome by correct diagnosis, early intervention for seizures, continual assess-ment for cognitive and behavioural disorders, appropriate school-ing, as well as effective family support, guidance, and therapy. Careful prospective follow-up studies are needed to demonstrate which interventions are most appropriate to speciﬁ  c types of epilepsy.

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seizures and psychogenic seizures: comparison of clinical and ictal characteristics. Neurology ,42, 1274–7.
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of mental health problems in children with epilepsy. Developmental 
Medicine and Child Neurology ,45, 292–5.
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epilepsy. Current Opinion in Neurology ,11, 115–18.
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laboratory and clinic. Epilepsia ,38, 12–30.

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9.2.2 Speciﬁ  c developmental 
disorders in childhood and adolescence
The term ‘speciﬁ  c developmental disorders’ includes a variety of 
severe and persistent difﬁ  culties in spoken language, spelling, read-

ing, arithmetic, and motor function. Skills are substantially below the expected level in terms of chronological age, measured intelli-gence, and age-appropriate education and cannot be explained by any obvious neurological disorder or any speciﬁ  c adverse psycho-
social or family circumstances. As the deﬁ  cits are quite substantial, 
analogies were initially made to neurological concepts and disor-ders such as word-blindness, alexia, aphasia, and apraxia, thus giv-ing rise to the notion that neurological deﬁ  cits are the aetiological 
basis of these disorders. Since this could not be demonstrated, the next step was to deﬁ  ne the disorders in a more functional way,

1623
 taking into account not only psychometric testing but also psycho-
social risk factors and the quality of schooling and education.
T oday, numerous ﬁ  ndings support the validity of the diagnostic 
concept of speciﬁ  c developmental disorders. These disorders and 
pervasive developmental disorders have the following features in common (ICD-10)
(1):
◆ An onset that invariably appears during infancy or childhood.
◆ An impairment or delay in the development of functions that 
are strongly related to biological maturation of the central nervous system.
◆ A steady course that does not involve the remissions and relapses 
that tend to be characteristic of many mental disorders.
Thus the term ‘speciﬁ  c developmental disorders’ reﬂ  ects the fact 
that the deﬁ  cits are circumscribed and relatively isolated against 
the background of an otherwise undisturbed psychological functioning.
In the multiaxial classiﬁ  cation of child and adolescent psychiatric

In the multiaxial classiﬁ  cation of child and adolescent psychiatric 
disorders,(2) speciﬁ  c developmental disorders are classiﬁ  ed on 
the second axis named ‘Specific disorders of psychological development’ , whereas pervasive developmental disorders are classiﬁ  ed on the ﬁ  rst axis (clinical psychiatric syndromes).
Based on the history and course of the disorders, two types can 
be distinguished:
◆ Disorders in which a phase of previously normal development 
has occurred prior to manifestation of the disorder. This, for example, applies to the Landau–Kleffner syndrome.
◆ An additional condition in which the abnormality was present 
from birth. This is especially true for autism. Autism is classiﬁ  ed 
in the category ‘pervasive developmental disorders’ , which are discussed elsewhere.
In DSM-IV ,
(3) nomenclature is somewhat different, but generally

In DSM-IV ,
(3) nomenclature is somewhat different, but generally 
includes disorders identical or similar to those in ICD-10.In DSM-IV , ‘communication disorders’ correspond to ‘speciﬁ  c 
developmental disorders of speech and language’ . However, they also include stuttering, which is not included in the corresponding category of ICD-10.
‘Learning disorders’ (DSM-IV) is the category that corresponds 
to speciﬁ  c developmental disorders of scholastic skills, and ‘motor 
skills disorder’ to ‘speciﬁ  c disorders of motor function’ .
Table 9.2.2.1 shows the terminology used in both classiﬁ  cation 
systems. The headlines of the two systems correspond; however, the subcategories show some differences.
Figure 9.2.2.1 shows a decision tree which includes the three 
main areas of dysfunction and addresses diagnosis and differential diagnosis.
Speciﬁ  c developmental disorders of speech 
and language

The main characteristic of these disorders is a disturbance of 
language acquisition from the early stages of development. The disturbance, however, is not directly attributable to neurological or speech mechanism abnormalities, sensory impairments, intellec-tual disability, or environmental factors.
(1)
There are three main problems in distinguishing these disorders 
from the normal state and other conditions:
1Differentiation from the normal state : the disorders must be 
distinguished from normal speech and language development, bearing in mind the great variations seen in the normal pattern. T o make the diagnosis, the disorder must clearly be clinically sig-
niﬁ cant, which can be determined by four main criteria: severity, 
course, pattern, and associated problems.

2Differentiation from intellectual disability (mental retardation) :
the degree of speech and language dysfunction must always be considered with respect to the child’s cognitive level.
3Differentiation from disorders due to sensory impairment 
or impairments of the central nervous systems : speech and 
language disorders resulting from severe deafness, specific 9.2.2 specific developmental disorders in childhood and adolescence
Table 9.2.2.1  Speciﬁ  c developmental disorders: a comparison of ICD-10 and DSM-IV NOS, not otherwise speciﬁ  ed
Speciﬁ  c developmental disorders of speech and language (F80)

 Speciﬁ  c speech articulation disorder (F80.0) Expressive language disorder (F80.1) Receptive language disorder (F80.2) Acquired aphasia with epilepsy (Landau–Kleffner syndrome) (F80.3) Other developmental disorders of speech and language (F80.8)Communication disorders
 Expressive language disorder (315.31)
 Mixed receptive–expressive language disorder (315.31)
 Phonological disorder (315.39) Stuttering (307.0)
 Communication disorder NOS (307.9)
Speciﬁ  c developmental disorders of scholastic skills (F81)
 Speciﬁ  c reading disorder (F81.0) Speciﬁ  c spelling disorder (F81.1)
 Speciﬁ  c disorder of arithmetical skills (F81.2)
 Speciﬁ  c disorder of scholastic skills (F81.3) Other developmental disorders of scholastic skills (F81.8)Learning disorders
 Reading disorder (315.00)

Speciﬁ  c disorder of scholastic skills (F81.3) Other developmental disorders of scholastic skills (F81.8)Learning disorders
 Mathematics disorder (315.1)
 Disorder of written expression (315.2)
 Learning disorder NOS (315.9)
Speciﬁ  c developmental disorder of motor function (F82) Motor skills disorder
 Developmental co-ordination disorder (315.4)
Mixed speciﬁ  c developmental disorders (F83)

SECTION 9  child and adolescent psychiatry 1624
neurological impairments, or structural brain abnormalities are 
not classiﬁ  ed in the category of speciﬁ  c developmental disorders 
of speech and language.
Speciﬁ  c speech articulation disorder
The main feature of the disorder is the child’s failure to use speech 
sounds appropriate for his or her mental age, while other language 
skills are within the normal range. Difﬁ  culties include errors in 
sound production and use, especially substitution of one sound for 
another. Difﬁ  culties in speech sound production usually interfere 
either with academic achievement or social communication. There 
are several degrees of severity reaching from mild or no impair-
ment of speech intelligibility to completely incomprehensible 
speech. Sound substitutions are considered less severe than sound 
omissions. The sounds most frequently misarticulated are those

omissions. The sounds most frequently misarticulated are those 
acquired later during speech development (l, r, s, z, th, ch). However, 
consonants and vowels that range early in the development 
sequence may be affected in younger children.
It is very important to relate the misarticulations to normal 
development. At the age of 4 years, errors in speech and sound pro-
duction are very frequent, but children are usually understood even 
by strangers. At 6 to 7 years of age, most speech sounds can be ade-
quately reproduced, and by the age of 11 to 12, children should be 
capable of almost all speech sounds.
In ICD-10, speech articulation disorder (F80.0) is classiﬁ  ed in the 
category ‘Speciﬁ  c developmental disorders of speech and language’ .

category ‘Speciﬁ  c developmental disorders of speech and language’ . 
The counterpart in DSM-IV is the category ‘Phonological disorder’ (315.39), classiﬁ  ed in the category ‘Communication disorders’ 
(see Table 9.2.2.1).
The leading feature, the age-appropriate misarticulation of speech 
sounds with the result that others have difﬁ  culties in understand-
ing the child, usually allows one to diagnose the disorder. There are 
three types of symptoms that can be observed: substitutions, omis-
sions, and distortions of speech sounds. The diagnosis should only 
be made if the severity of misarticulation is outside the limits of the 
normal variation for the child’s mental age. Further requirements 
are that non-verbal intelligence and expressive and receptive lan-
guage skills should be within the normal range.

Differential diagnoses include intellectual disability, hearing 
impairment, or other sensory deﬁ  cits or severe environmental 
deprivation.
Moderate to severe developmental articulation disorders can be 
found in 2 to 3 per cent of 6- and 7-year-old children, with less 
severe disorders even more frequent. The frequency of occurrence 
falls to 0.5 per cent by the time children are 17 years old 
(DSM-IV).
As it has been demonstrated that the disorder runs in families, it is 
assumed that genetic factors are important for its manifestation.
The prognosis is favourable if no other associated features such 
as hearing impairment, neurological conditions, cognitive impair-

ments, or psychosocial problems are present. However, the course Fig. 9.2.2.1 Speciﬁ  c developmental disorders. CNS, central nervous system.

1625
varies depending on the severity and the above-mentioned associ-
ated features.
Treatment is necessary and appropriate if the child is handicapped in his or her everyday life and cannot be understood by parents, siblings, or other persons. The focus of the therapy depends on whether speech articulation disorder is an isolated phenomenon or if other impairments or dysfunctions are present (e.g. developmen-tal disorder of motor functions). If it is an isolated phenomenon, functional speech therapy can be carried out on the principle that mispronounced sounds should not be repeated when correcting them, but substituted by the correctly pronounced sound.
(4) It is 
advisable to carry out this kind of therapy before the child enters school. If other disorders are present, a comprehensive therapeutic programme that includes speech therapy needs to be developed.
Expressive language disorder
(a) Clinical features and classiﬁ  cation

The main feature of this disorder is that the child’s ability to use 
expressive spoken language is reduced below the mental age appro-priate level, while language comprehension ranges within normal limits. Abnormalities in articulation may co-occur.
In ICD-10, the following symptoms are considered important 
for diagnosis (ICD-10, p. 237)
(1):
◆ delay of the development of expressive language (e.g. absence 
of single words by the age of 2 years, failure to generate simple two-word sentences by 3 years)
◆ restricted vocabulary development
◆ overuse of a small set of general words
◆ difﬁ  culties in selecting appropriate words and word substitutions
◆ short utterance length and immature sentence structure
◆ syntactical errors, especially omissions of word endings or preﬁ  x
◆ misuse of or failure to use grammatical features such as preposi-
tions, pronouns, articles, and verb and noun inﬂ  exions.

The DSM-IV criteria requires measures of expressive language 
development being substantially below those obtained from stan-dardized measures of both non-verbal intellectual capacity and receptive language development, interference with academic or occupational achievement, and the exclusion of mixed receptive–expressive disorder and pervasive developmental disorders.

The diagnosis is made by clinical observation, with special emphasis on expressive language functions and the use of individ-ually administered standardized tests of expressive language. The differential diagnosis should rule out mixed receptive–expressive language disorder (DSM-IV), characterized by an impairment of receptive language functions. Autistic disorder may also involve expressed language impairment, but autism can be distinguished by characteristic communication impairments. Finally, intellectual disability and sensory impairments (e.g. hearing impairment or other sensory deﬁ  cits) need to be ruled out, as well as severe 
environmental deprivation. The diagnosis is confirmed using intelligence tests, audiometric tests, neurological investigations, and a careful history. Finally, acquired aphasia needs to be ruled out. This can be done by assessing any medical condition that may have 
caused the disorder.

In the absence of thorough epidemiological studies, estimates suggest that between approximately 3 and 5 per cent of children may be affected by expressive language disorder of the develop-mental type. The acquired type seems to be less common.
DSM-IV distinguishes two types of expressive language disorders: the developmental type and the acquired type. In the developmental type, impairment of expressive language begins at a very early age and is not associated with neurological factors, while the acquired type occurs after a period of normal development and is caused by neurological or general medical conditions (e.g. head trauma, encephalitis). It is assumed that the developmental type is caused by genetic factors that inﬂ  uence language development.
The course depends on the type of disorder (developmental or

The course depends on the type of disorder (developmental or 
acquired type) and severity. Usually, the disorder can be diagnosed by the age of 3 years, while milder forms are often only detected later. According to DSM-IV ,
(3) approximately half of the children 
appear to outgrow the developmental type of expressive language disorder, while the other half have persistent difﬁ  culties. The out-
come of the acquired type depends on the severity and location of the brain pathology.
As causal treatment is not possible, treatment measures are based on general principles that have been found to be useful and effective in clinical practice.
1 The ﬁ  rst step is to explain clearly to parents the nature of the 
disorder and the fact that several other disturbances manifested by the child may be a result of the child’s communication deﬁ cit.
2 The best time to commence speech therapy depends upon the

2 The best time to commence speech therapy depends upon the 
severity of the disorder, the child’s cognitive and motivational structure, and other disorders that might be present. Instead of treating children too early (e.g. before the age of 3 years), offering advice and guidance to the parents is extremely important.
3 Treatment itself concentrates on teaching language skills using 
techniques such as imitation and modelling. The therapist should focus interventions selectively on the areas of difﬁ  culty, thus 
increasing the child’s phonological repertoire. Non-verbal com-munication techniques may be used if verbal communication is substantially impaired. But the therapist should always make sure that non-verbal communication does not dominate the ver-bal one.
4 In therapeutic programmes, everyday situations are now pre-

ferred to very structured programmes. This is because many therapists found that therapeutic progress during sessions was not transferred to everyday life situations. During structured treatment sessions the children are taught to give correct answers to questions that have nothing to do with their situation in every-day life, and it is now thought that structured language training may prevent them using language according to their needs.
(5)9.2.2 specific developmental disorders in childhood and adolescence

SECTION 9  child and adolescent psychiatry 1626
5 Alternative communication, such as sign language, should 
only be used if the child suffers from severe auditory compre-hension deﬁ  cits. The use of a sign language, however, is no longer 
regarded as an obstacle to the improvement of expressive language skills.
(6)
Receptive language disorder
This disorder is characterized by the child’s inability or reduced 
ability to understand language in a way appropriate for his or her mental age. As expressive language production depends on language comprehension; expressive language is also profoundly disturbed and abnormalities in word-sound production can be observed.
The diagnostic guidelines of ICD-10 include the following 
features:
◆ failure to respond to familiar names (in the absence of non-
verbal clues) by the ﬁ  rst birthday
◆ inability to identify at least a few common objects by 18 months

features:
◆ failure to follow simple, routine instructions by the age of 2 years
◆ inability to understand grammatical structures (e.g. questions, 
comparatives)
◆ lack of understanding of the more subtle aspects of language 
(tone of voice, gestures, etc.).
Owing to the disturbances in both receptive and expressive 
functions, the disorder is called ‘receptive–expressive language dis-order’ in DSM-IV . The diagnostic criteria require scores of both receptive and expressive language development substantially below those obtained from standardized measures of non-verbal intellec-tual capacity, interference with academic or occupational achieve-ment, and exclusion of pervasive developmental disorders.

Diagnosis is based on three factors: a careful history taken from the child’s parents, a thorough clinical investigation including neurological assessment and detailed speech and language assess-ment, and standardized tests measuring expressive and receptive language functions.
Differential diagnosis should rule out expressive language disor-
der (which is the case in the presence of language comprehension), speciﬁ  c speech articulation disorder, in which the receptive and 
expressive language functions are unimpaired, autism (which can be distinguished by the typical communication disturbance), intellectual disability, sensory deﬁ  cits, and severe environmental 
deprivation. These disorders can be excluded by intelligence tests, audiometric tests, neurological investigations, and taking a history.

Owing to the absence of epidemiological studies, the frequency with which the disorder occurs can only be estimated. According to estimations, the disorder occurs in up to 3 per cent of school-age children and is probably less common than expressive language disorder.
As in other developmental language disorders, there is evidence that genetic factors play the most important role in aetiology.
(7)The frequent association of disturbed language acquisition with adverse psychosocial factors in the family does not contradict a primarily genetic cause, as many children who grow up under these circumstances show entirely normal developmental patterns of speech and language skills.
(8)
The long-term prognosis is poor. Only half the patients in the sam-ple studied by Rutter et al.

(8)
(9) had normal conversational skills when 
they were in their twenties, and there was a decline in non-verbal IQ from childhood to adulthood. The course again depends on the type (developmental or acquired) and severity of the disorder. The disorder is usually detected before the age of 4 years, but earlier in severe cases. The prognosis is poorer than in expressive language disorder. As far as the acquired type is concerned, the prognosis varies depending on severity, location of brain pathology, the child’s age, and the level of language development prior to the disorder.

Treatment is generally undertaken along the same lines as in expressive language disorders. However, owing to the nature of the disorder, all factors that facilitate language comprehension should especially be encouraged. Non-verbal forms of communication such as sign language can be helpful.
Acquired aphasia with epilepsy (Landau–Kleffner 
syndrome)
The Landau–Kleffner syndrome is a rare disorder characterized by 
receptive and expressive language impairment and epileptic seizures, but retained general intelligence, and manifestation after a period of normal development, including language development. The onset of the disorder typically occurs between 3 and 7 years of age and is accompanied by paroxysmal electroencephalographic abnormalities, mainly bilateral spikes in the posterior temporal and parietal regions and epileptic seizures in about 80 per cent of cases.
(10) The loss of language may occur gradually over a period

(10) The loss of language may occur gradually over a period 
of months or abruptly within a few days or weeks.
Aphasia usually starts with receptive language problems 
occurring together with the characteristic electroencephalographic changes, followed by expressive language difﬁ  culties. Usually, the 
ﬁ rst sign is the impairment of receptive language functions with 
difﬁ culties in auditory comprehension. During the manifestation 
period, symptomatology is variable: some children become mute, others express jargon-like sounds, and some produce misar-ticulations and have difficulties in word fluency. During the manifestation period, emotional and behavioural symptoms are common; they can be regarded as a reaction to the loss of language functions and appear as anxiety reactions, acting-out behaviour, and aggression.
In DSM-IV , the condition is classiﬁ  ed in the category mixed 
receptive–expressive language disorder, acquired type.

The diagnosis can be based upon a detailed history of the child’s development, assessment of language functions, careful neurologi-cal assessment, and by electroencephalography. The differential diagnosis includes other types of acquired aphasia without epileptic seizures and electroencephalographic abnormalities, and

1627
disintegrative disorders of childhood such as dementia infantilis 
Heller (Heller’s syndrome) (see Chapter 9.2.2).
The prevalence of the disorder is unknown.
The aetiology is unknown. There is, so far, no indication of any genetic cause. Clinical characteristics suggest that an encephalitis might be considered a causal mechanism. The electroencephalo-graphic changes and the seizures are thought to cause the language and the behavioural and emotional problems.
(e) Treatment
So far, three different approaches to treatment have been undertaken:
1 Anticonvulsant treatment (mainly with carbamazepine): the 
frequency of seizures can be reduced to some extent with this medication, but paroxysmal electroencephalographic changes are not substantially inﬂ  uenced.
2 Corticosteroids have also been administered,
(11) but the beneﬁ  ts 
remain unclear.
3 Finally, surgical treatment by bilateral temporal transection has 
been attempted.(12,13)

Speciﬁ  c developmental disorders of 
scholastic skills
‘Speciﬁ  c developmental disorders of scholastic skills’ (ICD-10) or 
‘Learning disorders’ (DSM-IV) include disorders characterized by one or more signiﬁ  cant impairments in acquisition of reading, 
spelling, or arithmetical skills. ICD-10 suggests that the category ‘Mixed disorder of scholastic skills’ (F81.3) be used as an ill-deﬁ  ned, 
but necessary, category in which arithmetical and reading or spelling skills are signiﬁ  cantly impaired, although not because of 
general intellectual disability or inadequate schooling.
The disorders classiﬁ  ed in the category ‘Speciﬁ  c developmental 
disorders of scholastic skills’ ( SDDSS ) resemble speciﬁ  c disorders

disorders of scholastic skills’ ( SDDSS ) resemble speciﬁ  c disorders 
of speech and language. As in these latter disorders, normal pat-terns of skill acquisition are disturbed and detectable at an age when these functions are required. The disorders are not due to a lack of opportunity to learn or a consequence of brain trauma or 
disease, but represent a speciﬁ  c type of dysfunction in cognitive 
processing. The dysfunction affects speciﬁ  c skills, which can be 
distinguished from the cognitive functions that are usually in the normal range. As in other speciﬁ  c developmental disorders, the 
condition is more common in boys than in girls.
ICD-10 notes ﬁ  ve difﬁ  culties regarding diagnosis and differential 
diagnosis:
1 differentiation of the disorder from normal variations in

1 differentiation of the disorder from normal variations in 
scholastic achievement (this problem applies to all specific developmental disorders and was discussed in relation to speciﬁ  c 
developmental disorders of speech and language);
2 consideration of the normal developmental course;
3 interference with learning and teaching;4 underlying abnormalities in cognitive processing;5 uncertainties over the best way of subdifferentiating SDDSS.Based on these considerations, the following diagnostic guide-
lines for all SDDSS have been suggested (ICD-10):
◆Clinically signiﬁ  cant degree of impairment:  this is judged on 
the basis of severity (e.g. occurrence in less than 3 per cent of school children), developmental precursors (e.g. speech or language disorder in preschool years), and associated problems (e.g. inattention).

◆Speciﬁ  c impairment not explained solely by intellectual dis-
ability or by lesser impairments in general intelligence:  for this 
requirement to be met, individually administered and standard-ized IQ scholastic achievement tests are obligatory to demon-strate that the child’s level of achievement is substantially below the expected level compared to a child of the same mental age and IQ.
◆Developmental nature of the impairment:  this must be demon-
strated by the presence of the disorder during the early years of schooling and by exclusion of impairment acquired later. The child’s history of school progress is decisive in this respect.

◆Absence of external factors that could explain the impairment:SDDSS are thought to be mainly based on factors intrinsic to the child’s development, and not due to inadequate schooling or any other environmental factors such as absence from school or edu-cational discontinuities. However, such conditions may occur, making the diagnostic process difﬁ  cult.
◆Exclusion of visual and hearing impairments:  by deﬁ  nition, 
SDDSS do not occur as a result of impairment of sensory func-tion, such as visual or hearing impairment.
The main differential diagnostic task is distinguishing SDDSS 
from neurological disorders (e.g. alexia, aphasia, agraphia, apraxia) or impairments that also could inﬂ  uence the development of

from neurological disorders (e.g. alexia, aphasia, agraphia, apraxia) or impairments that also could inﬂ  uence the development of 
scholastic skills (e.g. emotional disorder). In cases of normal child development prior to the manifestation of a deﬁ  ned neurological 
disorder, differential diagnosis is not difﬁ  cult. However, if minor 
neurological signs (soft signs) were diagnosed previously, indepen-dent of any deﬁ  ned disorder, and the ﬁ  ndings persist, it may be 
difﬁ cult to distinguish recent symptoms from previous ones. In 
such cases, associated disorders or symptoms should be classiﬁ  ed 
separately in the appropriate neurological section of the classiﬁ  ca-
tion systems.
Speciﬁ  c reading disorder
The ICD-10 classiﬁ  cation system distinguishes between ‘Speciﬁ  c

The ICD-10 classiﬁ  cation system distinguishes between ‘Speciﬁ  c 
reading disorder’ and ‘Specific spelling disorder’ . In DSM-IV , ‘Specific reading disorder’ is distinguished from ‘Disorder of Written Expression’ . The latter is not identical with the ICD-10 cat-egory ‘Speciﬁ  c spelling disorder’ , insofar as that disorder excludes 
children whose sole problem is one of handwriting.
The main feature of this disorder is a speciﬁ  c and signiﬁ  cant 
impairment in the development of reading skills, which is not solely accounted for by mental age, visual acuity problems, or inadequate schooling.
(1)
Other functions may also be affected:
◆ word recognition
◆ reading comprehension skills9.2.2 specific developmental disorders in childhood and adolescence

SECTION 9  child and adolescent psychiatry 1628
◆ oral reading skills
◆ performance of tasks requiring reading
In many cases, spelling difﬁ  culties continue into adolescence and 
persist in adulthood, even when reading skills improve consider-ably. The history of children with speciﬁ  c reading disorder fre-
quently reveals a speciﬁ  c developmental disorder of speech and 
language. Symptoms of these disorders may still be present at ele-
mentary school when the speciﬁ  c reading disorder is ﬁ  rst diag-
nosed. Additional frequently associated problems include poor school attendance and problems with social adjustment.
The DSM-IV criteria for reading disorder state that reading 
achievement as measured by standardized tests should be substan-tially below the expected level and that the disturbance should interfere with academic achievement or activities of daily living that require reading skills.

The diagnosis is made on the basis of the ICD-10 and/or DSM-IV criteria, which are similar. The ICD-10 diagnostic guidelines require the following:
◆ A reading performance below the level that is expected on the 
basis of age, general intelligence, and school placement. For clin-ical purposes, usually 1.5 standard deviations below the expected level is regarded as a requirement for the diagnosis. For research purposes, two standard deviations are used.
◆ Performance to be assessed by individually administered stan-
dardized tests of reading accuracy, latency, and comprehension.
◆ Errors demonstrated in oral reading skills and deﬁ  cits in reading 
comprehension. Errors in oral reading include:
(a)  omissions, substitutions, distortions, or additions of words 
or parts of words;
(b) slow reading rate;
(c)  false starts, long hesitations, or ‘loss of place’ in text, and 
inaccurate phrasing;

(d) reversals of words in sentences or of letters within words.
Deﬁ cits in reading comprehension include:
(a) an inability to recall facts that have been read;(b) inability to draw conclusions or interferences from material 
that has been read;
(c)  use of general knowledge as background information, rather 
than of information from a particular story, to answer ques-
tions about a story that has been read.
(c) Comorbidity and associated features
It is important to analyse the features of the disorder with a longi-
tudinal perspective. Thus, several associated disorders can be 
observed: emotional problems during the early school years; hyper-
activity and conduct disorders in later childhood and adolescence. 
Additional frequent features include low self-esteem, adjustment

Additional frequent features include low self-esteem, adjustment 
problems at school, and problems in peer relationships. In about 
40 per cent of children with reading and/or spelling disorder, other disorders of clinical relevance are present. After ﬁ  nishing school, 
this rate decreases to 30 per cent, which includes a high proportion of antisocial behaviour and delinquency.
(14)(d) Epidemiology
Speciﬁ  c reading and spelling disorder occur in about 4 per cent of 
8- to 10-year-old children, when deﬁ  ned as two standard deviations 
below non-verbal IQ.(15,16) By using a wider definition, the 
rates are approximately 7 to 8 per cent, with a predominance of boys (2:1).
Currently, four main aetiological factors have been discussed:
1 genetic inﬂ  uences;
2 deﬁ  cits in central information processing;
3 general psychosocial factors;
4 speciﬁ  c learning conditions.

Familial clustering in dyslexia was recognized a few years after 
the ﬁ  rst description of the disorder by Hinselwood in 1895. A child 
with an affected parent has a risk of between 40–60 per cent of developing dyslexia.
(17) This risk is increased when other family 
members are also affected. There is estimated to be a 3 to 10-fold increase in the relative risk for a sibling ( λ
s), with an increase in λs
being observed when stricter criteria are applied.(18)
Twin studies have conﬁ  rmed that genetic factors are substantially

Twin studies have conﬁ  rmed that genetic factors are substantially 
responsible for the familial clustering of dyslexia. It is generally accepted that the proportion of inherited factors involved in the development of dyslexia is between 40–80 per cent, the highest estimates being reported for the phenotype dimensions word reading (up to 58 per cent) and spelling (70 per cent).
(19) Whereas 
shared environmental effects are low for word reading, for with reading, and spelling correlated traits, for example, phonological awareness, shared environmental is substantially higher at about 14 per cent. Based on genome-wide linkage analyses nine candidate gene regions (DYX1-9) could be identiﬁ  ed. Most replicated are 
two regions, 6p22, and 15q21. More recently, four candidate genes, DCDC2, KIAA0319, ROBO1, and DYX1C1 were identiﬁ  ed by

two regions, 6p22, and 15q21. More recently, four candidate genes, DCDC2, KIAA0319, ROBO1, and DYX1C1 were identiﬁ  ed by 
systematic association analyses. All these genes play a functional role in neuronal migration making them promising candidate genes for dyslexia. However, a functional relevant mutation has not been identiﬁ  ed yet.
(19)
The hypothesis of deﬁ  cits in central information processing is 
based on behavioural and neuroimaging studies that identiﬁ  ed 
cognitive processes that are impaired in dyslexics individuals. These are impaired visual processing, auditory processing, speech percep-tion, phonologic processing, orthographic processing, and motor coordination.
(20) The mainstream hypothesis is a phonological 
processing deﬁ  cit supported by longitudinal, intervention, and

processing deﬁ  cit supported by longitudinal, intervention, and 
brain imaging studies. Among the latter, the importance of left hemispheric specialization has been widely discussed in the litera-ture, either suggesting maturational lag of the left hemisphere or a structural deﬁ  cit in white and grey matter.
(20)
General psychosocial factors may also play a role in the manifes-
tation of speciﬁ  c reading and spelling disorder. However, the inﬂ  u-
ence seems to be rather marginal. The same applies, more or less, to the special learning condition, because severe deﬁ  cits in schooling 
are excluded by deﬁ  nition as a main cause of these disorders. 
However, given a genetic predisposition for speciﬁ  c reading or 
spelling disorder, poor learning conditions at school and at home may contribute to the manifestation of these disorders. In summary, the different factors responsible for the manifestation of speciﬁ  c

1629 9.2.2 specific developmental disorders in childhood and adolescence
reading and speciﬁ  c spelling disorder can be best understood in 
terms of a vulnerability model, in which several genetic predisposi-tions, on the one hand, and general psychosocial factors and special learning conditions, on the other, interact with one another.
More than 40 longitudinal follow-up studies have shown similar results:
◆ There is a high persistence of reading and spelling problems, 
phonological difﬁ  culties, and slowness in word recognition.(23,24)
◆ Retarded readers make poorer progress than backward 
readers.(25)
◆ On the other hand, considerable progress is possible in oral 
reading and reading comprehension.(26)
As far as schooling is concerned, a substantial proportion of chil-
dren with speciﬁ  c reading disorder remain behind the school level

dren with speciﬁ  c reading disorder remain behind the school level 
of their age group. However, there is a difference regarding social background. Children from middle-class homes more frequently show a positive educational outcome compared with children from socially disadvantaged homes.
(27)
An epidemiological study in Germany(16) showed that only 3 per 
cent of children with speciﬁ  c reading disorder were able to attend 
high school and more than 50 per cent remained at the lowest nor-mal school level. At the age of 18, the rate of unemployment was three times as high as in a normal control group.
As mentioned above, treatment is difﬁ  cult because the disorder 
tends to persist. Nevertheless, the following principles have been found to be useful:
1 Treatment should start as early as possible in order to avoid a 
sense of failure and low self-esteem.

2 The treatment should focus on individual instruction and teach-
ing sessions in basic phonetic and other skills such as reading, spelling, and writing. This needs to be done in an age-appropri-ate way based on the principles of learning theory and starting at a very low level to avoid disappointment and a sense of failure. There are several programmes used in different countries based on these principles, sometimes using computers.
3 Although very popular methods based on training basic percep-
tual skills like ﬁ  gure-ground discrimination, tone discrimina-
tion, temporal auditory processing have not been proven by empirical studies.
4 Even when feelings of failure and, consequently, low self-esteem

4 Even when feelings of failure and, consequently, low self-esteem 
are present, the instruction in basic skills is the appropriate approach. The child’s psychological and learning situation deserves special attention. Psychotherapeutic measures alone are not successful.
5 Parental support is extremely important. Therefore, the parents 
should not only be educated in detail about the disorder, but also encouraged to listen to their children reading from school books. This has been shown to be a successful approach.
(28)
6 There is no speciﬁ  c medication to improve reading and spelling 
skills, but there is some indication that stimulants may be helpful for poor readers who simultaneously suffer from attention-deﬁ cit hyperactivity disorder.Speciﬁ  c spelling disorder
In ICD-10, the main characteristic of this disorder is a speciﬁ  c and

In ICD-10, the main characteristic of this disorder is a speciﬁ  c and 
signiﬁ  cant impairment in the development of spelling skills in the 
absence of a history of speciﬁ  c reading disorder, which is not solely 
accounted for by low mental age, visual acuity problems, or inade-quate schooling. The children have difﬁ  culties in spelling orally 
and writing words correctly. For this diagnosis, the following criteria are required (ICD-10):
◆ The spelling performance of the child should be signiﬁ  cantly 
below the expected level regarding age, general intelligence, and school placement. This has to be assessed individually by administration of a standardized spelling test.
◆ The reading skills should be within the normal range and there 
should be no history of preceding reading difﬁ  culties.
◆ The spelling difﬁ  culties should not be due to grossly inadequate 
teaching, to sensory deﬁ  cits, or to neurological disorders or dys-

functions. They should not be acquired, either as a result of neu-ropsychiatric or any other disorders.
In DSM-IV , there is no category that corresponds exactly to the 
ICD-10 category ‘Speciﬁ  c spelling disorder’ . The DSM-IV category 
that most closely resembles ‘Speciﬁ  c spelling disorder’ is ‘Disorder of 
written expression’ , as deﬁ  ned by measured writing skills substan-
tially below the expected level, interference with academic achieve-ment, and, in the case of a sensory deﬁ  cit, writing skills greater than 
the difﬁ  culties usually associated with sensory deﬁ  cits.
It is uncertain whether a pure spelling disorder as described in

It is uncertain whether a pure spelling disorder as described in 
ICD-10 actually exists or whether spelling skills usually overlap with other functions that constitute scholastic skills. It is, however, possible to assess the different functions separately, as several studies show.
The diagnosis is made according to the criteria mentioned above and by the administration of standardized spelling tests.
Speciﬁ  c disorders of arithmetical skills
The main clinical feature of this disorder (also called dyscalculia) is 
a speciﬁ  c impairment in arithmetical skills that cannot be explained 
on the basis of general intellectual disability or inadequate school-ing. Dyscalculia is a difﬁ  culty in learning and remembering arith-
metic facts and executing calculation procedures, with immature problem-solving strategies, long solution times, and high error rates.

(29) A number of different skills may be impaired, as under-
standing or naming mathematical terms, operations, or concepts, and decoding written problems into mathematical symbols.
The impairment affects basic computational skills of addition, 
subtraction, multiplication, and division, whereas other functions such as reading and writing or motor skills are within the normal range (except in mixed disorder of scholastic skills). The arithmeti-cal difﬁ  culties vary, but in most cases include the following features 
(ICD-10):
◆ difﬁ  culties in understanding the conc epts under lying ar ithmetical
operations
◆ difﬁ culties or lack of understanding of mathematical terms or signs
◆ difﬁ  culties in recognizing numerical symbols

SECTION 9  child and adolescent psychiatry 1630
◆ difﬁ  culties in carrying out arithmetical manipulations
◆ difﬁ  culties in aligning numbers or symbols when performing 
calculations
◆ poor spatial organization of arithmetical calculations
◆ reduced ability to learn multiplication tables satisfactorily.
The diagnosis is made according to ICD-10 (Speciﬁ  c disorders 
of arithmetical skills) or DSM-IV criteria (Mathematics Disorder )
and the diagnostic guidelines. The ICD-10 guidelines require the following criteria:
◆ The child’s arithmetical performance should be signiﬁ  cantly 
below the expected level on the basis of age, general intelligence, and school placement, assessed by an individually administered standardized arithmetical test.
◆ Reading and spelling skills should be within the normal range 
expected for the child’s mental age, also tested by an individually administered standardized test.
◆ The difﬁ  culties in arithmetical skills should not be mainly due

◆ The difﬁ  culties in arithmetical skills should not be mainly due 
to grossly inadequate teaching or the direct effects or defects of visual, hearing, or neurological functions and should not be acquired as sequelae of neurological, psychiatric, or other disorders.
The DSM-IV criteria follow the same principles as with other 
speciﬁ  c developmental disorders. Required criteria include mathe-
matical ability substantially below the expected level, interference with academic achievement, and in the case of a sensory deﬁ  cit, the 
difﬁ culties in mathematical ability greater than the difﬁ  culties usu-
ally associated with sensory deﬁ  cits.
The diagnosis is made according to the above-mentioned criteria

The diagnosis is made according to the above-mentioned criteria 
in the ICD-10 and DSM-IV systems. Differential diagnosis must rule out acquired arithmetical disorder (acalculia), arithmetical difﬁ culties associated with a reading or spelling disorder, and 
arithmetical difﬁ  culties as a result of inadequate teaching.
It is estimated that between 3 and 6 per cent of all schoolchildren 
suffer from a speciﬁ  c arithmetical disorder.(30) The sex ratio is 
approximately equal, in some studies girls are found to be more often affected than boys.
(31) An important correlate of maths 
disorder is dyslexia. It is estimated that 40 per cent of dyslexics also have maths disorder.
(31)
Dyscalculia has not been studied with the same intensity as dyslexia. Therefore, knowledge about aetiology, course, and out-come is limited.

(31)
Numerical abilities, including arithmetic, are mediated by areas 
in the parietal lobe. In functional imaging studies performed during mental calculation tasks, a pattern of bilateral activation in the prefrontal, premotor, and parietal cortices has been obser-ved.
(32) Neuropsychological evidence indicates that numerical 
processing is localized to the parietal lobes bilaterally, in particu-lar the intra-parietal sulcus
(33) and is independent of other abili-
ties. A reduced volume of grey cortical matter in dyscalculicindividuals was found in the sulcus intraparietalis of the left hemisphere.
(34,35)There have been a few studies into genetic contributions to

(34,35)There have been a few studies into genetic contributions to 
mathematical cognitive ability. Most have studied the possible genetic aetiology of mathematics disorder, at least partly because of its comorbidity with reading disorder.
(36)
Results from twin studies were consistent with a genetic basis for 
mathematics disorder whether combined with reading disability or not and estimates of high heritability of mathematical ability were obtained in a sample of twins with normal intelligence ascertained for reading disability and family samples.
(37,38)
So far developmental dyscalculia is likely to be the result of the 
failure of these brain areas to develop normally and can best be deﬁ ned as a deﬁ  cit in the representation or processing of speciﬁ  cally 
numerical information.
(39)
A substantial proportion of children with speciﬁ  c disorder of 
arithmetical skills have associated emotional problems and difﬁ  -

(39)
culties in social interactions. It is not quite clear whether these difﬁ culties are secondary complications of the speciﬁ  c difﬁ  culties 
of arithmetical skills.
As a matter of fact, speciﬁ  c disorder of arithmetical skills is only 
diagnosed at the end of the ﬁ  rst year or the beginning of the second 
year of elementary school, because of the necessity of these skills at that time. Especially in cases when the disorder is associated with a high IQ, children may initially compensate for the difﬁ  culties with 
the result that the dysfunction is discovered only in the third year of elementary school or later. According to some studies,
(40,41)
children with speciﬁ  c disorder of arithmetical skills show poor 
visuospatial abilities and also have difﬁ  culties in complex and

(40,41)
visuospatial abilities and also have difﬁ  culties in complex and 
motor tasks. Share et al.(42) compared these results with their own. 
Deﬁ cits of right hemisphere functioning were found, but only in 
boys. These results suggest that boys and girls with speciﬁ  c disorder 
of arithmetical skills should be studied separately. A further inter-esting result is the association of the disorder with anxiety.
(43) This 
association is more pronounced in those children in whom arith-metical skills are substantially impaired compared with relatively good reading and spelling skills.
The treatment of speciﬁ  c disorders of arithmetical skills follows 
the same general lines as treatment of speciﬁ  c reading disorder. All

the same general lines as treatment of speciﬁ  c reading disorder. All 
treatment components have to focus on the training of skills that are impaired in a way that keeps the child motivated. Treatment strategies should focus on the mathematical disability itself or the mathematics anxiety with which the disorder is frequently associated. In many cases, both facets need to be included in the treatment programme. When treating the mathematical disability according to the child’s individual proﬁ  le of impairment, four 
aspects should be emphasized: semantic memory, procedural difﬁ  -
culties, visuospatial difﬁ  culties, and difﬁ  culties with mathematical 
problem-solving.
(44) Mathematics anxiety requires a more psycho-
therapeutic approach using relaxation techniques, with the aim of reducing anxiety prior to and during maths lessons in order to avoid a sense of failure.

Mixed disorders of scholastic skills
In ICD-10, this is speciﬁ  ed as an ill-deﬁ  ned and inadequately con-
ceptualized, but necessary residual, category of disorders in which both arithmetical and reading or spelling skills can be signiﬁ  cantly

1631
impaired, and in which the disorder cannot be explained in terms 
of general intellectual disability or inadequate schooling. This category covers disorders that meet the criteria of ‘Speciﬁ  c disorder 
of arithmetical skills’ (F81.2) and either ‘Speciﬁ  c reading disorder’ 
(F81.0) or ‘Speciﬁ  c spelling disorder’ (F81.1). As has been explained 
earlier, in the case of a mixed disorder of scholastic skills, it is speciﬁ  c arithmetical disorder that seems to dominate both in sever-
ity and with respect to associated psychopathological features.
Speciﬁ  c developmental disorder of 
motor function
Clinical features and classiﬁ  cation
Many children to whom this category applies, were previously 
diagnosed as having ‘minimal brain dysfunction’ . This term is no longer used. The essential clinical features of the disorder include the following (ICD-10):
◆ An impairment of motor coordination that is signiﬁ  cantly below

◆ An impairment of motor coordination that is signiﬁ  cantly below 
the expected level on the basis of age and general intelligence assessed by an individually administered and standardized test.
◆ The difﬁ  culties in coordination should already have been present 
early in development.
◆ They should not be acquired and not be a direct result of deﬁ  cits 
of vision or hearing or of any neurological disorder.
Variability of ﬁ  ne or gross motor coordination is great. The mile-
stones of motor development are usually delayed. In many cases, there is an association with speech difﬁ  culties, especially articula-
tion. Parents usually report that the child was slow in learning to sit, run, hop, climb stairs, and ride a bicycle. Many children also have difﬁ  culties in learning to tie shoelaces, fasten and unfasten 
buttons, and throw or catch balls. Some children may be generally clumsy in ﬁ  ne and gross movements others tend to have their main

buttons, and throw or catch balls. Some children may be generally clumsy in ﬁ  ne and gross movements others tend to have their main 
difﬁ culty with ﬁ  ne movements and coordination. In many cases, 
drawing skills are also impaired and the child’s difﬁ  culties are 
particularly obvious during ball games, which require a consider-able amount of gross motor coordination.
The DSM-IV criteria are similar, and emphasize a substantial 
backlog of motor coordination, significant interference with academic achievement, and require general medical conditions and pervasive developmental disorders to be ruled out.
There is growing evidence that speciﬁ  c developmental disorders 
of motor function are a quite heterogeneous group that needs to be 
subclassiﬁ  ed.
(45)
Diagnosis is made according to the criteria and guidelines in ICD-10 
and DSM-IV . Differential diagnosis should rule out speciﬁ  c neuro-

(45)
logical disorders, which can be done with a careful history and neurological examination, pervasive developmental disorders, which can be distinguished by the criteria of these disorders, or attention-deﬁ  cit hyperactivity disorder. The latter can be distin-
guished by their pronounced distractibility and impulsivity rather than impairment of motor coordination.
According to an estimation in DSM-IV about 6 per cent of 5- to 11-year-old children suffer from the disorder.Aetiology
There are two main factors said to be responsible for the aetiology, genetic inﬂ  uences and brain damage. As far as genetic inﬂ  uences 
are concerned, there are no valid studies that conﬁ  rm this assump-

tion. Regarding brain damage, the question arises whether early brain damage can result in a speciﬁ  c impairment of motor func-
tions, while other functions are within normal limits.
(46–48) As this 
appears very unlikely, comorbidity with other disorders should be considered the norm and speciﬁ  city regarded as the exception.
(49)
The few follow-up studies have shown that children who suffer 
from the disorder between 5 and 10 years of age show a high persis-tence of motor problems in adolescence. Almost all children who were identiﬁ  ed as having had motor difﬁ  culties at elementary 
school, had similar problems as teenagers.
(50–52)
Treatment
Treatment measures should focus on two main facets: the difﬁ  cul-
ties and impairments in the different motor functions, and the associated social and emotional difﬁ  culties. The ﬁ  rst facet requires

ties and impairments in the different motor functions, and the associated social and emotional difﬁ  culties. The ﬁ  rst facet requires 
an active functional treatment of motor functions focusing on the child’s individual difﬁ  culties. Programmes are available for this 
kind of treatment, which is usually carried out by physiotherapists and occupational therapists.
(53)
In treating the second facet, therapists are confronted with the 
child’s insecurity, which is a direct result of motor difﬁ  culties, poor 
body scheme, avoidance reactions of peers and classmates, and frequent feelings of inferiority and a low self-esteem.
(54) These 
associated problems need to be addressed in psychotherapy, in addi-tion to programmes that focus solely on training motor functions.
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in children—do they grow out of it? A ten-year follow-up study. Developmental Medicine and Child Neurology ,33, 55–68.
52. Cantell, M.H., Smyth, M.M., and Ahonen, T.P . (1994). Clumsiness

52. Cantell, M.H., Smyth, M.M., and Ahonen, T.P . (1994). Clumsiness 
in adolescents: educational, motor a nd social outcomes of motor 
delay detected at ﬁ  ve years. Special Issue of Adapted Physical Activity 
Quarterly ,11, 115–29.
53. Schoemaker, M.M., Hijlkema, M.G.J., and Kalverboer, A.F. (1994). 
Physiotherapy for clumsy children: an evaluation study. Developmental Medicine and Child Neurology ,36, 143–55.
54. Kalverboer, K.F. (1998). On the relevance of speciﬁ  c classiﬁ  cations of 
disorders with particular focus on DCD, developmental coordination 
disorder. In Perspectives on the classiﬁ  cation of speciﬁ  c developmental 
disorders  (eds. J. Rispens, T.A. van Yperen, and W. Yule), pp. 265–78. 

1633
9.2.3 Autism and the pervasive 
developmental disorders
The pervasive developmental disorders (PDDs) are characterized 
by patterns of deviance and delay in social-communicative devel-opment in the ﬁ  rst years of life, which are associated with restricted 
patterns of interest or behaviour. The prototypic PDD is childhood autism; other conditions included in the PDD class in ICD-10
(1)
include Rett’s syndrome, childhood disintegrative disorder, Asperger’s syndrome, and atypical autism. Except for one additional category in ICD-10 (hyperkinetic stereotyped movement disorder), the dis-orders included in ICD-10 and DSM-IV
(2) are essentially identical. 
In this chapter each of these conditions will be reviewed in terms of their clinical features, deﬁ  nition, epidemiology, course, and aetiol-
ogy; ﬁ  nal sections of the chapter address aspects of treatment and 
prevention for the group of disorders as a whole (Box 9.2.3.1).
Childhood autism

Autism was ﬁ  rst recognized by Kanner(3) in his report of 11 children 
with ‘autistic disturbances of affective contact’ . He emphasized two essential diagnostic features: autism and difﬁ  culties with change; 
but he also noted atypical language (when language was present at all). He used Bleuler’s term ‘autistic’ to convey the children’s social isolation. Although children with autism had undoubtedly been previously observed,
(4) it was Kanner’s particular genius to so pre-
cisely describe the condition. False leads for research arose since the term autism introduced an unintended confusion with schizophre-nia. Also, Kanner assumed that the children had normal intellectual potential. Subsequently, it became clear that autism and schizophre-nia were distinct and that autism was often associ ated with intellec-tual disability.

(5) Although describing autism as inborn, Kanner 
mentioned that parents were very well educated and successful. In turn this led to the idea, common during the 1950s, that autism might somehow result from deviant patterns of care by unusually successful parents. A large body of evidence shows that this is most certainly not the case.
(6) It is clear that families of children with 
autism come from all social classes and circumstances(7) and that 
the original impression had been the result of referral bias.
Social deﬁ  cits of a particular type remain a hallmark of autism. 
The nature of this deﬁ  cit varies, somewhat, over time but remains a 9.2.3 autism and the pervasive developmental disorders
source of great disability to the affected individual throughout 
life.(8) In younger and more impaired individuals there may be

life.(8) In younger and more impaired individuals there may be 
little interest in social interaction; less impaired individuals may come to a passive acceptance of social interaction while older and more cognitively able individuals are more likely to seem highly eccentric and one-sided.
(9) Difﬁ  culties are observed in the use of 
eye contact or other non-verbal social cues, in social emotional reciprocity and empathy, in activities involving shared interests with others, and with peer relationships (see Table 9.2.3.1). As Rutter
(10) suggested, these problems do not simply reﬂ  ect cognitive

(10) suggested, these problems do not simply reﬂ  ect cognitive 
impairment, which is present in about 60 per cent of individuals affected. Abnormalities in communication (not only in language) are also observed. In a substantial minority (perhaps 30 per cent) of cases, the child never acquires the capacity for communicative speech; among individuals who do talk, various unusual features of language are observed such as echolalia, idiosyncratic language, deﬁ cits in prosody, and pronoun reversal.
(11) Deﬁ cits in pragmatic 
language are particularly striking. As with the social disturbance, the deﬁ  cits observed are not solely due to intellectual disabilities. 
Various unusual behaviours are s ubsumed under the term ‘resistance

to change’ . These behaviours include literal resistance to change (‘insistence on sameness’), stereotyped and repetitive motor man-nerisms, strict adherence to non-functional routines, and interest in non-functional parts of objects. Various other features may be observed, such as unusual sensitivities to aspects of the environ-ment and attachments to unusual objects.
Deﬁ nition
In the 1950s and 1960s there was disagreement about autism, 
e.g. was it a form of schizophrenia or psychosis? Gradually evidence began to accumulate that suggested the role of central nervous system dysfunction in pathogenesis—for example, high risk for developing seizures. Differences in clinical features, onset and course, and family history also supported the distinctiveness of autism apart from childhood schizophrenia.
(12,13) By 1978,

(12,13) By 1978, 
there was a substantial body of work on the validity of autism. Rutter synthesized this in his inﬂ  uential deﬁ  nition of autism,
(10)
which required the presence of patterns of delay and deviance 
in the areas of social and language development that were not simply the result of developmental delay along with the group of unusual behaviours subsumed under Kanner’s term ‘insistence on sameness’ . Onset before 30 months of age was required. In ICD-9
(14) infantile autism was still termed a psychotic condition 
but by 1980 the highly influential DSM-III(15) appeared and 
recognized autism as a condition apart from schizophrenia, includ-ing it in a new class of disorders—the pervasive developmental disorders. The latter term has been the topic of some debate, although a better term has yet to be proposed and, in any case, the term PDD has now come into general usage in both DSM and ICD.
(16,17)
The name chosen in DSM-III (‘Infantile autism’) was consistent

(16,17)
The name chosen in DSM-III (‘Infantile autism’) was consistent 
with Kanner’s original report but reﬂ  ected a lack of developmental 
orientation; these concerns were addressed in DSM-III-R,(18) which 
provided a detailed, and more developmentally oriented, set of diagnostic guidelines. Unfortunately, this deﬁ  nition proved overly 
inclusive and it became apparent that additional work would be needed. Further impetus was given to this effort by pending changes in ICD-10
(1) and DSM-IV . Accordingly, an international 
ﬁ eld trial was undertaken.(19) Based on the results of this ﬁ  eld trial Box 9.2.3.1  The pervasive developmental disorders
 Childhood autism/autistic disorder
 Rett’s disorder
 Childhood disintegrative disorder
 Asperger’s disorder PDD-NOS/atypical autism

SECTION 9  child and adolescent psychiatry 1634
autism is deﬁ  ned (see Table 9.2.3.1) on the basis of characteristic 
problems in three areas: social interaction, communication and play, and restricted patterns of interest. By deﬁ  nition, autism must 
be present by the age of 3 years. ICD-10 provides for various ways in which a diagnosis of atypical autism can be made—for example, because of failure to meet age of onset or behavioural criteria. Data on this system suggest that it has good agreement with the diagnoses of experienced clinicians, avoids the problem of the overdiagnosis of autism in the most mentally handicapped persons, and has reasonably good reliability.
Epidemiology and demographics
Over 40 epidemiological studies of autism and related conditions have been conducted with prevalence estimates ranging from 0.7 per 10 000 to 72.6 per 10 000.
(20) In his recent 2005 review,

(20) In his recent 2005 review, 
Fombonne notes that prevalence rates are negatively correlated with sample size and there is an apparent trend for increased rates over time. Various considerations (including changes in deﬁ  nition) 
complicate the interpretation of increased rates. In this review, Fombonne suggests that a reasonable estimate of prevalence is 13 per 10 000 (Box 9.2.3.2). Although higher rates of 1 in 150 are 
reported if broad deﬁ  nitions are used.
A number of studies, including both epidemiological and clini-
cally referred samples, report higher rates of autism in boys than in girls (typically 3.5:1 or 4:1). This ratio varies with IQ level, i.e. fem-ales with autism who have IQs in the normal range are probably Table 9.2.3.1  ICD-10 criteria for childhood autism (F84.0)

A. Abnormal or impaired development is evident before the age of 3 years in at least one of the following areas:
  1 receptive or expressive language as used in social communication;
  2 the development of selective social attachments or of reciprocal social interaction  3 functional or symbolic playB.  A total of at least six symptoms from (1), (2), and (3) must be present, with at least two from (1) and least one from each  of (2) and (3)
  1 Qualitative impairment in social interaction is manifested in at least two of the following areas:   (a) failure adequately to use eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction   (b)  failure to develop (in a manner appropriate to mental age, and despite ample opportunities) peer relationships that inv olve a mutual sharing of interests, 
activities, and emotions

   (c)  lack of socio-emotional reciprocity as shown by an impaired or deviant response to other people’s emotions; or lack of modulation of behaviour 
according to social context; or a weak integration of social, emotional, and communicative behaviours
   (d)  lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g. a lack of showing, b ringing, or pointing out to other 
people objects of interest to the individual)
  2 Qualitative abnormalities in communication in at least one of the following areas:   (a)  delay in or total lack of development of spoken language that is not accompanied by an attempt to compensate through th e use of gestures or mime as 
an alternative mode of communication (often preceded by a lack of communicative babbling)
   (b)  relative failure to initiate or sustain conversational interchange (at whatever level of language skill is present), in  which there is reciprocal responsiveness to

(b)  relative failure to initiate or sustain conversational interchange (at whatever level of language skill is present), in  which there is reciprocal responsiveness to 
the communications of the other person
   (c) stereotyped and repetitive use of language or idiosyncratic use of words or phrases   (d) lack of varied spontaneous make-believe play or (when young) social imitative play  3 Restricted, repetitive, and stereotyped patterns of behaviour, interests, and activities are manifested in at least one of the following:
   (a)  an encompassing preoccupation with one or more stereotyped and restricted patterns of interest that are abnormal in con tent or focus; or one or more 
interests that are abnormal in their intensity and circumscribed in nature though not in their content or focus

   (b) apparently compulsive adherence to speciﬁ  c non-functional routines or rituals   (c)  stereotyped and repetitive motor mannerisms that invo lve either hand or ﬁ  nger ﬂ  apping or twisting or complex whole-bo dy movements:
   (d)  preoccupations with part-objects or non-functional elements of play materials (such as their odour, the feel of their s urface, or the noise or vibration they 
generate)
C.  The clinical picture is not attributable to the other varieties of pervasive developmental disorders; speciﬁ  c developmenta l disorder of receptive language (F80.2) 
with secondary socio-emotional problems, reactive attachment disorder (F94.1), or disinhibited attachment disorder (F94.2); men tal retardation (F70–F72) with 
some associated emotional or behavioural disorders; schizophrenia (F20.-) of unusually early onset; and Rett’s syndrome (F84.12 ).

Taken from Disorders of psychological development (criteria for research) , pp. 154–5. © World Health Organization, www.who.int
Box 9.2.3.2  Epidemiology of autism and related conditions
 Autism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13 per 10 000
 Rett’s disorder. . . . . . . . . . . . . . . . . . . . . . . . . .  1 per 10 000 girls Childhood disintegrative disorder . . . . . . .1.9 per 100 000 Asperger’s syndrome . . . . . . . . . . . . . . . . . . . . 4 per 10 000 PDD-NOS/atypical autism . . . . . . . . . . . . . . .1 per 150
Source: Cohen, D.J. and Volkmar, F.R. (eds.) (2005) Handbook of autism and pervasive 
developmental disorders  (3rd edn.) Wiley, New York.

1635
20 times less common than males.(21) The explanation for this sex 
difference remains unclear. It is possible that the degree of insult required to produce autism in females must be greater than for males, but other hypothesis have been raised. Ethnic and cultural differences have been little studied.
(20,22)
Although childhood autism is a chronic disability, there is some suggestion that with early intervention and remediation outcome is improving.
(23) For example, the number of individuals with 
either a ‘good’ or ‘fair’ outcome is now about 50 per cent—a note-worthy increase since 1980.
(24) However, even in the highest func-
tioning individuals marked social problems persist.
Changes in the degree of social relatedness, communication, and

Changes in the degree of social relatedness, communication, and 
self-help skills are observed with increases in developmental level. Seizure disorders are observed in up to 25 per cent of individuals and may have their onset at any point, but adolescence and early childhood are particularly common times.
(25) Factors that predict 
long-term outcome include the presence of some communicative speech by the age of 5 or 6 years, and non-verbal intellectual level.
Aetiology
Early interest centred on the possibility that experiential factors might somehow cause autism, but a host of research ﬁ  ndings sug-
gests that this is not the case. Rather, a fundamental disturbance in the central nervous system is implicated.
(a) Psychological factors
Disabilities affecting attentional mechanisms, arousal, sensory def-

icits, memory management, and complex information processing, among others, have been proposed as ‘primary’ deﬁ  cits underlying 
the social impairment in autism. Although each of these helps us understand some aspects of the condition, none has, as yet, pro-vided a more comprehensive account of the condition as a whole.
(26) Among the most inﬂ  uential recent theories attempting 
to do that is the hypothesis that posits a lack of a central drive for coherence in children with autism, with the consequent focus on dissociated fragments of their environment rather than integrated ‘wholes’ , leading to a fragmentary and overly concrete experience of the world.
(27) Another cognitive account of autism posits that 
the commonly found difﬁ  culties in abstracting rules, inhibiting 
irrelevant responses, shifting attention, and proﬁ  ting from feed-

back as well as in maintaining relevant information ‘on-line’—the so-called ‘executive functions’—underlie the social, communicative, and behavioural disabilities in autism.
(28) Although both these the-
ories—‘weak central coherence’ and ‘executive dysfunction’—pro-vide insightful new views of well-known clinical features, neither phenomena can be seen as speciﬁ  c to autism relative to other devel-
opmental disorders.
Probably the most inﬂ  uential current cognitive hypothesis focus-

es on mechanisms directly impacting on social understanding. This view, the ‘theory of mind’ hypothesis, posits that autism is caused by the child’s inability to attribute mental states such as beliefs and intentions to others. Devoid of this ability, individuals with autism are thought to be unable to infer the thoughts and motivations of others, thus failing to predict their behaviour and adjust their own actions accordingly, which results in a lack of reciprocity in com-munication and social contact.
(29) Although more than 50 studies 
have documented such deﬁ  cits in autism, there are still many limitations to this hypothesis. For example, more able individuals

have documented such deﬁ  cits in autism, there are still many limitations to this hypothesis. For example, more able individuals 
with autism do exhibit ‘theory of mind’ skills—and yet may be totally unable to utilize this capacity in their spontaneous social adjustment. Such phenomena suggest that factors other than a cog-nitive understanding of mental phenomena are required for a per-son to meet the demands of everyday social life. For example, the ‘enactive mind’ hypothesis focuses on early emerging and highly conserved mechanisms of socialization that precede the advent of mentalizing abilities, and which culminate in the development of joint attention and perspective taking skills.
(30) Of great interest in 
the past few years has been the conﬂ  uence of experimental psycho-

logical paradigms and functional neuroimaging studies focusing on the same constructs. This new trend is leading to new insights into brain systems subserving basic social mechanisms such as gaze behaviour, face processing, social-affective responses, and thinking about other people’s intentions and beliefs,
(31) all of which are 
greatly compromised in autism.
(b) Biological factors
The importance of biological factors in the pathogenesis of autism is suggested by several lines of evidence. Autism has been associated with a host of medical conditions; but the absence of population data and rigorous diagnostic assessment makes such associations difﬁ cult to interpret. For example, early reports suggested an asso-
ciation with congenital rubella, but this now seems questionable given the diagnostic dilemmas and the observation that ‘autistic-like’ features diminish over time.

(32) Gillberg(33) argues that medical 
conditions may be associated with autism in as many as one-third of the cases, but Rutter and colleagues
(34) suggest that a more reason-
able ﬁ  gure would be roughly 10 per cent of all cases. The strongest 
associations are with fragile X syndrome and tuberous sclerosis—both conditions having a strong genetic component (Box 9.2.3.3).
Fragile X syndrome is an X-linked intellectual disability syn-

drome involving a mutation characterized by a triplet repeat of cytosine–guanine–guanine (CGG) that may amplify with succeed-ing generations. It is associated with a characteristic facial appear-ance, enlarged testicles, intellectual disability, and some autistic features. Early reports suggesting high rates of fragile X in autism have now been modiﬁ  ed; fragile X affects perhaps 1 to 2 per cent of 
all individuals with autism.
(20)
The autosomal dominant disorder tuberous sclerosis is charac-
terized by abnormal tissue growth, or benign tumours (hamarto mas),

(20)
terized by abnormal tissue growth, or benign tumours (hamarto mas), 
in the brain and in other organs. The condition, which may affect 1 in 10 000 individuals, is variably expressed; the phenotype ranges from minor skin problems or seizures to severe intellectual disabil-ity with intractable seizures. The rate of this condition in autism (0.4–2.8 per cent) is signiﬁ  cantly increased.
(20)
Autism is a strongly genetic condition. Studies of monozygotic 
and dizygotic twins revealed much higher levels of concordance for monozygotic relative to dizygotic twin pairs, but also elevated 9.2.3 autism and the pervasive developmental disorders
Box 9.2.3.3  Medical conditions associated with autism
 Seizure disorder (epilepsy)
 Fragile X syndrome Tuberous sclerosis

SECTION 9  child and adolescent psychiatry 1636
rates of concordance in dizygotic twins relative to population 
rates.(35) General studies suggest that the recurrence risk of autism 
in siblings is in the order of between 2 and 10 per cent—which is a substantial increase in risk over population rates. There also appear to be higher rates of social and language problems and rigid patterns of behaviour in siblings and close relatives, raising the possibility that what is inherited is a broader phenotype reminis-cent of autism but which also may reﬂ  ect a more general predispo-
sition to developmental difﬁ  culties. Recent work also suggests 
elevated rates of anxiety and mood disorders in family members. Speciﬁ  c modes of inheritance remain unclear. It now appears that

elevated rates of anxiety and mood disorders in family members. Speciﬁ  c modes of inheritance remain unclear. It now appears that 
several interacting genes are probably involved in the pathogenesis of autism. Efforts are underway to identify susceptibility genes and trace their impact on brain development. Although several studies have shown increased rates of pre-, peri-, and neonatal complica-tions in children with autism, it is possible that some of these difﬁ culties may reﬂ  ect a genetic vulnerability in the child or that 
there may be an interaction of genetic and perinatal factors.
(35)
A recent report has noted the presence of placental abnormalities in pregnancies of children with autism.
Attempts have been made to identify neuropathological and

(35)
Attempts have been made to identify neuropathological and 
neuroanatomical correlates of autism. Areas of interest have included the cortical areas responsible for language and social interaction (frontal and temporal lobes) as well as the neostriatum and cerebellum.
(36) The report of reduced cerebellar size in the neocer-
ebellar vermal lobules VI and VII has not proven readily replicable. Some individuals with autism have enlarged brains and head sizes, with some evidence that abnormal growth occurs in the ﬁ  rst 2 years 
of life.
(37) Neuropathological studies have suggested p ossible cellular 
changes in areas of the brain such as the hippocampus and amyg-dala and changes in the cytoarchitecture of the brain, e.g. in the arrangement of cortical ‘minicolumns’ .
Various neurotransmitter systems have been studied. Probably

Various neurotransmitter systems have been studied. Probably 
the most robust ﬁ  nding has been the observation that about one-
third of the children with autism have increased peripheral levels of serotonin. This ﬁ  nding is not speciﬁ  c to autism and its signiﬁ  -
cance remains unclear.
(38) Studies of other neurotransmitters such 
as dopamine produced inconsistent ﬁ  ndings. The possible involve-

ment of dopamine is suggested by the high levels of stereotyped behaviours in autism—behaviours, which can be induced in animals by the administration of agents (stimulants) that affect levels of dopamine in the brain. Agents such as the neuroleptics, which block dopamine receptors, are effective in reducing the ste-reotyped and hyperactive behaviours of many autistic children. Another hypothesis has centred on the possible role of endogenous opioids, in that overproduction of such compounds might lead to social withdrawal and unusual sensitivities and behaviours. This has led to the administration of opioid antagonists such as naltrex-one in autism; unfortunately results have been disappointing. Studies of the immune system in autism have been relatively uncommon and ﬁ  ndings inconsistent.
Rett’s syndrome

In 1966, Andreas Rett described an unusual syndrome in girls 
characterized by a history of initial normal development, subse-quent head growth deceleration, and the development of speciﬁ  c 
clinical ﬁ  ndings such as breathing difﬁ  culties, movement problems, 
and some features suggestive of autism.
(39) His ﬁ  ndings were 
replicated and extended by Hagberg and colleagues.(40) As more extensive information became available it became clear that the 
more ‘autistic-like’ phase of Rett’s syndrome was relatively brief, but this was a major rationale for its inclusion in the PDD class.
(41)
Early pre- and perinatal histories are generally unremarkable in Rett’s syndrome, as is very early development. Usually within the ﬁ rst or second year of life development begins to slow or actually 
regress and various motor problems—including characteristic hand-washing stereotypies start to develop.
(42) A signiﬁ  cant loss

(42) A signiﬁ  cant loss 
of developmental skills occurs and head growth decelerates.(40)
The potential for misdiagnosis of autism is greatest during this time; during school age developmental regression often stabilizes and children are more socially responsive. As individuals with Rett’s syndrome approach adolescence they are frequently subject to increased spasticity, scoliosis, loss of ambulation, bruxism, hyperventilation, areophagia, apnoea, and seizures.
(43) Although 
debated,(44) the inclusion of Rett’s syndrome in the PDD class 
reﬂ ects an awareness of the confusion with autism and the impor-
tance of including the condition somewhere.(41)
Deﬁ nition
Various diagnostic criteria for Rett’s syndrome have been 
developed.(45) As presently deﬁ  ned in ICD-10 (see Table 9.2.3.2)

Deﬁ nition
developed.(45) As presently deﬁ  ned in ICD-10 (see Table 9.2.3.2) 
the condition develops after some months of normal development; head circumference is normal at birth but begins to decelerate between 5 and 48 months. Characteristic midline hand-wringing or hand-washing stereotypies develop and purposeful hand movements are lost.
Prevalence estimates range from 1 per 12 000 to 1 per 23 000 females; cases are observed in all racial and ethnic groups.
(46, 47)
Rett’s syndrome may account for one-quarter to one-third of progressive developmental disabilities among females.
(46) A small 
number of cases have now been reported in males.
Various clinical stages of the condition have been identiﬁ  ed.(42)
Early developmental losses may be subtle initially but become more

Early developmental losses may be subtle initially but become more 
marked with time. Purposeful hand movements are often then lost, as are speech skills. Ataxia and gait abnormalities are noted in those 
Table 9.2.3.2 ICD-10 criteria for Rett’s syndrome (F84.2)
A.  There is an apparently normal prenatal and perinatal period and apparently 
normal psychomotor development through the ﬁ  rst 5 months and normal 
head circumference at birth.
B.  There is a deceleration of head growth between 5 months and 4 years and 
loss of acquired purposeful hand skills between 5 and 30 months of age that is associated with concurrent communication dysfunction and impaired 
social interactions and the appearance of poorly co-ordinated/unstable gait 
and/or trunk movements.
C.  There is severe impairment of expressive and receptive language, together 
with severe psychomotor retardation.

D.  There are stereotyped midline hand movements (such as hand-wringing or 
‘hand-washing’) with an onset at or after the time when purposeful hand 
movements are lost.
Taken from Disorders of psychological development (criteria for research) , pp. 154–5. 
© World Health Organization, www.who.int

1637
patients who had acquired the ability to walk, unusual breathing 
patterns (hyperventilation and/or apnoea), and seizures may also be observed. While social and communication skills may improve in middle childhood motor problems are more pronounced. During the ﬁ  nal phase (roughly after age 10) progressive scoliosis 
and spasticity are observed, while cognitive function stabilizes and seizure activity may diminish. There is a dearth of information on adults with the condition. There does appear to be an increased risk of sudden death due to seizures and/or respiratory difﬁ  culties.
(48)
Aetiology
Rett(39) originally speculated that the condition might be 
associ ated with high peripheral ammonia levels, but this was incorrect. Recent work identiﬁ  ed mutations in the MeCP2 gene 
as the cause of Rett syndrome in most cases; this gene has a major role in regulating various genes during brain development.
(49)
Childhood disintegrative disorder

(49)
Shortly after the turn of the twentieth century a special educator working in Vienna, Theodor Heller,
(50) reported children who 
had a period of several years of normal development prior to a marked regression with loss of skills in multiple areas and minimal recovery. He initially termed the condition dementia infantilis; subsequently it has been referred to as Heller’s syndrome, disinte-grative psychosis, or childhood disintegrative disorder.
(51) Once 
it develops the condition is indistinguishable from autism,(52) but 
it is accorded separate diagnostic status since it appears distinctive in terms of onset and course.
In this condition an ‘autistic-like’ clinical picture develops after a prolonged period of normal development.
(50) More than 100 cases

(50) More than 100 cases 
have now been reported; the condition is rare but probably under-diagnosed.
(51) Essential clinical features include a relatively long 
period of normal development followed by a marked developmen-tal regression and development of various ‘autistic-like’ features; onset is typically between the ages of 3 and 4 years.
Onset can be relatively abrupt or more gradual, and a premonitory 
phase of non-speciﬁ  c anxiety or agitation may be observed. Parents 
often note associations between the onset of the condition 
and various psychosocial or medical events but such associations 
are probably correlational rather than causative.
(53) Once estab-
lished it resembles autism.(52) Given the behavioural similarity to

lished it resembles autism.(52) Given the behavioural similarity to 
autism, it might be argued either that the condition does not warrant separate diagnostic recognition or that the condition is inevitably the result of an association with some progressive medi cal 
condition. However, the pattern of onset is quite distinctive, the outcome appears to be even worse than in autism, and usually even with very intensive medical evaluations no general medical condition accounting for the regression is identiﬁ  ed.
(52)
Deﬁ nition
Criteria for the disorder are listed in Table 9.2.3.3. By deﬁ  nition the 
disorder cannot coexist with autism or another other explicitly deﬁ ned pervasive developmental disorder, schizophrenia, elective 
mutism, or the syndrome of acquired aphasia with epilepsy.

Epidemiological data are quite limited. Some limited data suggest a prevalence rate of 1 in 100 000. Initially cases seemed to be equally distributed between males and females, but it now seems likely that 
cases of Rett’s syndrome may have been included in early case series. Recent reviews have noted a preponderance of males.
(20)
In about 75 per cent of cases the deterioration reaches a plateau, in that there is no further loss of skills, but subsequent gains tend to be minimal. Thus the child who previously was normally socially related, spoke in full sentences, and was toilet-trained becomes indifferent to social interaction, loses all expressive language and toilet skills, and remains mute and relatively low functioning.
(52)

(52)
In the remainder of cases there is more limited recovery, for exam-ple the child regains the capacity to speak but only in single words or only echoes language. If a progressive metabolic or neuropatho-logical process is present, the developmental progression may con-tinue until death ensues; such cases often have a later onset.
(54) Life 
expectancy otherwise appears to be normal. In a very small num-ber of cases signiﬁ  cant recovery has been noted.
Aetiology
Various lines of evidence suggest the importance of neurobio-
logical factors in pathogenesis. Occasionally medical conditions such as the neurolipidoses, metachromatic leukodystrophy, Addison–Schilder’s disease, and subacute sclerosing panencephalitis are associated with the condition. Rates of electroencephalographic abnormalities and seizure disorders are of roughly the same frequency as seen in autism.9.2.3 autism and the pervasive developmental disorders

Table 9.2.3.3 ICD-10 criteria for other childhood disintegrative 
disorder (F84.3)
A.  Development is apparently normal up to the age of at least 2 years.
The presence of normal age-appropriate skills in communication, social relationships, play, and adaptive behaviour at age 2 years or later is required for diagnosis.
B.  There is a deﬁ  nite loss of previously acquired skills at about the time of 
onset of the disorder. The diagnosis requires a clinically signiﬁ  cant loss of 
skills (not just a failure to use them in certain situations) in at least two 
of the following areas:
 1 expressive or receptive language 2 play
 3 social skills or adaptive behaviour
 4 bowel or bladder control
 5 motor skills.
C.  Qualitatively abnormal social functioning is manifested in at least two 
 1  abnormalities in reciprocal social interaction (of the type deﬁ  ned 
for autism)
 2  qualitative abnormalities in communication (of the type deﬁ  ned 

 3  restricted, repetitive, and stereotyped patterns of behaviour, interests, 
and activities, including motor stereotypes and mannerisms
 4 a general loss of interest in objects and in the environment.
D.  The disorder is not attributable to the other varieties of pervasive 
developmental disorder; acquired aphasia with epilepsy (F80.6); 
elective mutism (F94.0); Rett’s syndrome (F84.2); or schizophrenia (F20.-).
Taken from Disorders of psychological development (criteria for research), pp. 154–5

SECTION 9  child and adolescent psychiatry 1638
Asperger’s syndrome
The condition known as Asperger’s syndrome was described by a 
paediatrician with interest in intellectual disability, Hans Asperger,
(55) who reported on four boys with marked social prob-
lems, unusual perseverative interests, and motor clumsiness but with seemingly good verbal and cognitive abilities. Like Kanner, Asperger used the word autism (autistic psychopathy) to describe this condition. His concept, however, had points of difference, as well as similarity, to autism. For example, verbal abilities tended to be an area of strength, concerns typically did not arise until later in the preschool period, and there was a tendency for the condition to run in families—particularly in fathers. Lorna Wing’s
(56) report of

(56) report of 
Asperger’s work and publication of a series of cases brought wider attention to the diagnostic concept. The validity of this condition, particularly apart from higher-functioning autism, remains the topic of much debate. A major complication has been the marked differences in deﬁ  nition of the conditions and its potential overlap 
with other diagnostic concepts (e.g. schizoid personality,
(57) non-
verbal learning disabilities,(58) semantic–pragmatic disorder,(59)
and right hemisphere learning problems).(60) As a result, the litera-
ture on this condition is difﬁ  cult to interpret, although areas of 
potential differences from autism have been identiﬁ  ed, such as 
neuropsychological proﬁ  les(61) and family history.(62)
This condition is characterized by impairments in social interac-

tion and restricted interests and behaviours as seen in autism. However, the child’s early development is marked by lack of any clinically signiﬁ  cant delay in spoken or receptive language, cognitive 
development, self-help skills, and curiosity about the environment. Consistent with Asperger’s
(55) original report, all-absorbing and 
intense circumscribed interests as well as motor clumsiness are typical, but are not required for diagnosis. The validity of this condition, apart from high-functioning autism and PDD not otherwise speciﬁ  ed (PDD-NOS) is controversial. Available research 
is difﬁ  cult to interpret given the markedly different ways in which

is difﬁ  cult to interpret given the markedly different ways in which 
the diagnostic concept has been used. Differences are more likely to be noted relative to autism if a rather stringent diagnostic approach is used. Evidence for external validity of the condition relative to autism includes differences in neuropsychological proﬁ  les, patterns 
of comorbidity, and family history.
Persons with Asperger’s syndrome often exhibit a somewhat 
eccentric social style rather than the more passive or aloof style noted in autism; for example, they may engage others in very one-
sided conversations about their area of special interest. They maybe 
overly reliant on rigid rules for social interaction and may fail to ‘see the forest for the trees’ in social matters (e.g. an appreciation of exactly when the usual rules do not apply is as important as when they do). Their social oddity and lack of ﬂ  exibility is a source of 
much disability.

While early speech-communication skills are apparently normal, 
certain aspects of communication become more deviant over time. Prosody may be poor, rate of speech may also be unusual, or it may have a somewhat disorganized, tangential, and circumstantial quality. The issue of whether such persons are at increased risk for thought disorder and psychosis remains unresolved, but some part of this impression probably reﬂ  ects communication problems.
It is rather typical for patients to amass considerable factual 
information about their topic of interest, which they pursue with great intensity; Asperger originally observed that family life may

information about their topic of interest, which they pursue with great intensity; Asperger originally observed that family life may 
revolve around the topic of special interest. He also suggested that motor clumsiness was present and, although not required for the diagnosis, there is often a history of motor delay and persistent motor awkwardness—for instance, the child may talk before he walks, have trouble fastening fastener, catching a ball, learning to ride a bicycle, engaging in cursive handwriting, and may also display stiffened gate.
Differences in neuropsychological proﬁ  les have been reported.
(63)
A stringent diagnostic approach may suggest areas of relative 
strengths (auditory and verbal skills and rote learning) and weak-ness (visuomotor and visuoperceptual skills); this pattern differs from that observed in higher-functioning individuals with autism

(64) and the heritability of social difﬁ  culties may be even 
greater in Asperger’s syndrome than in autism.(62)
Interest in the condition has revolved around the possibility that 
it might represent a transition between autism and other disorders such as schizophrenia. Associated conditions have included depres-sion, anxiety and other mood problems, violence, and other psychotic conditions.
(63) Unfortunately, almost all of this literature 
rests on case reports; controlled studies are needed.
Deﬁ nition
The ICD-10 criteria for Asperger’s syndrome are given in Table 9.2.3.4. 
As presently deﬁ  ned the social deﬁ  cit is the same as in autism. In 
contrast to autism, however, early language, cognitive, and other skills develop typically early in life. By deﬁ  nition, the case does not

contrast to autism, however, early language, cognitive, and other skills develop typically early in life. By deﬁ  nition, the case does not 
meet the criteria for childhood autism. Miller and Ozonoff
(65) note 
that several aspects of the current deﬁ  nition can be problematic; 
Asperger consistently felt that the syndrome he described differed from Kanner’s autism (1979). Thus the current deﬁ  nition almost 
certainly will be reﬁ  ned (or discarded) in future editions of ICD 
and DSM.
Table 9.2.3.4 ICD-10 criteria for Asperger’s syndrome (F84.4)
A.  There is no clinically signiﬁ  cant general delay in spoken or receptive 
language or cognitive development. Diagnosis requires that single words 
should have developed by 2 years of age or earlier and that communicative 
phrases be used by 3 years of age or earlier. Self-help skills, adaptive behaviour, and curiosity about the environment during the ﬁ  rst 3 years 
should be at a level consistent with normal intellectual development.

should be at a level consistent with normal intellectual development. 
However, motor milestones may be somewhat delayed and motor clumsiness is usual (although not a necessary diagnostic feature). Isolated 
special skills, often related to abnormal preoccupations, are common, but 
are not required for the diagnosis.
B.  There are qualitative abnormalities in reciprocal social interaction (criteria 
as for autism).
C.  The individual exhibits an unusual intense circumscribed interest or 
restricted, repetitive, and stereotyped patterns of behaviour interests and activities (criteria as for autism; however, it would be less usual for these to 
include either motor mannerisms or preoccupations with part-objects or 
non-functional elements of play materials).
D.  The disorder is not attributable to other varieties of pervasive 
developmental disorder; simple schizophrenia; schizotypal disorder; 
obsessive-compulsive disorder; anankastic personality disorder; reactive and

obsessive-compulsive disorder; anankastic personality disorder; reactive and 
disinhibited attachment disorders of childhood.
Taken from Disorders of psychological development (criteria for research), pp. 154–5 

1639
Estimates of prevalence vary markedly depending on the stringency 
of the deﬁ  nition used. A stringent approach to diagnosis would 
suggest a rate in the order of 1 in 2000 or so, but a much less stringent approach may yield one in several hundred.
(66)
Asperger(55) originally reported the condition only in boys, alth-
ough Wing reported on girls with the condition. There does appear to be a male predominance in the order of 20 to 1; similar sex ratios are observed in autism not associated with intellectual disability.
Asperger’s original(55) impression was of favourable long-term 
prognosis.(67) Many individuals can attend regular school with some 
additional support; unfortunately such children may be seen as eccentric and are often prime targets for being victimized. Better verbal skills can mislead educators about the child’s vulnerability in other areas, and difﬁ  culties academically may be mis attributed to

wilful non-compliance. There is the impression that these individu-als are capable of greater degrees of personal and occupational self-sufﬁ ciency than those with autism, but deﬁ  nitive data are lacking. It 
does appear that the social difﬁ  culties persist into adulthood.
(68)
Aetiology
Although the cause of Asperger’s syndrome remains unknown, 
the report of high rates of the condition in family members and the reports of occasional familial associations with autism suggests the potential importance of genetic factors. Neurobiological informa-tion on the condition is limited. The potential association of the condition with speciﬁ  c neuropsychological proﬁ  les is of some 
interest.
Atypical autism/PDD not otherwise 
speciﬁ  ed
Recent editions of both ICD and DSM have included a ‘subthresh-
old’ category (termed either atypical autism or pervasive develop-mental disorder not otherwise speciﬁ  ed—PDD-NOS). In some

old’ category (termed either atypical autism or pervasive develop-mental disorder not otherwise speciﬁ  ed—PDD-NOS). In some 
ways, this notion has historical links to earlier diagnostic concepts.
(23)
In practice, the term atypical autism in ICD-10 and the term PDD-NOS in DSM-IV refer to what is a residual diagnostic category. ICD-10 provides the possibility for various forms of special coding—for example, failure to meet the onset criteria for autism, failure to meet developmental/behavioural criteria, or failure to meet both.
Research on this diagnostic category has been less advanced than 
that for other disorders—no doubt reﬂ  ecting the problems intrin-
sic to ‘subthreshold’ disorders. Several attempts have recently been made to identify potential subgroups within the rather heteroge-neous disorder, but none has yet achieved general acceptance. Various attempts have been made to identify speciﬁ  c subgroups

within this broader category.
(69) It is sometimes the case that 
social and/or communicative skills are relatively preserved but the child exhibits unusual sensitivities, affective responses, and thought processes. It is likely that the term presently encompasses a number of conditions, which may be identiﬁ  ed in the future.
Autism and related PDDs must be differentiated from each other, 
from the speciﬁ  c developmental disorders (e.g. of language), from intellectual disability not associated with PDD, and from other 
conditions. In intellectual disability not associated with PDD, social and communicative skills are typically on a par with the child’s 
overall intellectual ability. Diagnostic differentiation can be most challenging in persons with severe and profound intellectual disabil-ity where assessment is more difﬁ  cult and stereotyped movements 
common. Occasionally language and other speciﬁ  c developmental

common. Occasionally language and other speciﬁ  c developmental 
disorders may be confused with autism/PDD. Usually, however, the child’s social abilities are preserved and the child is very communi-cative non-verbally. Schizophrenia rarely has its onset in childhood and almost never before the age of 5 years.
On occasion, selective mutism or social anxiety disorder may be 
confused with a PDD (particularly PDD-NOS/atypical autism). However, in selective mutism the child can speak in some situa-tions. Similarly, children with anxiety in social situations will usually not exhibit the other symptoms characteristic of autism/PDD. The unusual behaviour and interests of children with obses-sive–compulsive disorder may be taken to suggest autism or PDD, but social and language-communication skills are preserved.
In considering the differential diagnosis of conditions that present

In considering the differential diagnosis of conditions that present 
with regression it is important to review carefully previous diagnostic evaluations. Occasionally, progressive neuropatho logical conditions may have their onset in childhood. In the Landau–Kleffner syndrome (acquired aphasia with epilepsy) social skills should be relatively pre-served even in the face of an extensive aphasia.
Sometimes children who have experienced marked neglect may 
present with social difﬁ  culties, initially suggesting autism or PDD. 
However, in reactive attachment disorder the history of severe neglect is observed and, as the name of the condition implies, social deﬁ cits should remit substantially if an appropriate and nurturing 
environment is provided.
Treatment
Over the past decade a relatively substantial body of research on treatment of autism has appeared. Recent summaries of this work are available.
(70) Much of this work relates to behavioural and edu-

cational interventions although a body of well-controlled studies of psychopharmacological agents has appeared as well.
(71)
Children with autism and other PDDs generally require an inten-
sive and highly structured intervention programme. More able children may be able to tolerate regular classroom situations, with appropriate support, but more impaired children often need higher levels of teacher supervision and a more intensive classroom setting.
(72) For lower-functioning children areas of priority include 
the ability to tolerate adult guidance and intrusion, to follow routines, to develop communicative abilities, and move from asso-ciative to more conceptual learning strategies.
(73) The classroom

(73) The classroom 
setting can be important, as children with PDD can be readily distracted by extraneous stimuli. The tendency of such children to rely on routines can be used effectively to help promote more systematic learning. Generalization of skills learned is particularly important since the child may have difﬁ  culties in applying skills 
learned in new settings. Speech and communication are a critically important aspect of any intervention programme.
(11) Te ch n i qu e s 
to foster communication through non-verbal means such as sign language, picture-exchange, visual schedules, and other augmenta-tive methods can be very helpful to non-verbal children.
(74) The

(74) The 
use of such methods does not preclude, and in fact may foster, the use of spoken communication.9.2.3 autism and the pervasive developmental disorders

SECTION 9  child and adolescent psychiatry 1640
Behaviour modiﬁ  cation techniques are helpful in increasing the 
frequency of desired behaviours while simultaneously diminishing problem behaviours. Typically, a functional analysis of the target behaviour is initially performed, and then a plan developed for prompting or decreasing the behaviour.
(73) While there is general 
agreement that children with autism/PDD proﬁ  t from a behav-
iourally based intervention, there is more controversy over the degree to which progress can be made; for instance, there have been some claims for dramatic improvement and even ‘cures’ of autism.
Neuroleptics have been the most intensively studied psychophar-
macological agents in this population, and there have been several well-designed double blind, placebo-controlled trials.
(71) The main 
mechanism of action appears to be dopamine-receptor blockade. The agents may reduce maladaptive behaviours such as stereo-typies,

(75) but side effects include sedation, irritability, and move-
ment problems (including tardive dyskinesia). Recently, interest has centred on the newer atypical neuroleptics.
(76)
Goals for treatment include promoting learning and reducing behaviours that interfere with learning. Treatment is best based on a comprehensive view of the child and his or her strengths and areas of need. A structured and individualized intervention pro-gramme is needed. Various professionals such as speech patholo-gists, special educators, occupational and physical therapists may be involved.
(72,73) Goals for intervention will vary depending on

(72,73) Goals for intervention will vary depending on 
developmental level, life circumstance, and clinical context—for example, vocational factors will be more important during adoles-cence, and for individuals with conditions like Rett’s syndrome the efforts of other professionals (orthopaedists and respiratory therapists) may be needed.
For higher functioning and older individuals the acquisition and 
generalization of social skills are particularly important. The use of rehearsal and social scripts may be indicated. T eaching must be explicit and can include modelling and rehearsal within individual instruction and small group settings, with the use of naturalistic settings to encourage generalization whenever possible. For higher functioning students, including those with Asperger’s syndrome, this can include explicit analyses of challenging social situations, 
videotaping for self-observation, role playing, and the use of indi-
vidualized social stories.
(77)

(77)
There is no evidence that unstructured psychotherapy is useful 
in autism and related conditions. Structured and supportive psychotherapy may be appropriate for some carefully selected, higher-functioning individuals, particularly if it focuses on explicit problem-solving strategies for frequently troublesome situations.
Pharmacotherapy interventions are not curative, but they may 
provide considerable help with speciﬁ  c problematic symptoms.
(71)
The best evidence relates to the atypical neuroleptics but data on 
other agents are less substantive. The balance of potential beneﬁ  ts 
and risks should be considered, and informed consent obtained from parents or, whenever possible, the affected child.
Mood stabilizers and antidepressants have sometimes been used, 
given the increase in affective lability, anxiety, and depression in

given the increase in affective lability, anxiety, and depression in 
individuals with autism and PDDs. However, the response to antidepressants has been somewhat variable. Lithium and other mood stabilizers are sometimes used clinically, particularly if there 
is a strong family history of bipolar disorder, but there have been few controlled studies of these agents.
Selective serotonin-reuptake inhibitors (SSRIs) were of initial 
interest in autism, given the repeated reports of high group levels of peripheral serotonin in this population as well as of the high levels of repetitive behaviours observed in this group (i.e. reminis-cent of those seen in obsessive–compulsive disorder). Several reports have suggested that, at least in adults, these agents may be 
helpful in lowering the levels of obsessive–compulsive-like behav-

iours, although activation is sometimes observed; Studies of children have been less frequent, but there is some suggestion that they may also respond.
(71)
Various other agents have been used in autism, including 
anxiolytics, β-blockers, clonidine, and naltrexone. Unfortunately, 
it is difﬁ  cult to draw ﬁ  rm conclusions from the limited data avail-
able, but at present the clinical efﬁ  cacy of these agents is not 
well established in this population. Surprisingly few studies have systematically evaluated the use of stimulants in autism. However, the observation that these agents induce stereotyped behaviours in animals would suggest their potential for increasing levels of stereotyped behaviours.

At present information on the prevention of autism and related PDDs is clearly quite limited. Apart from the association with two strongly genetic conditions (fragile X syndrome and tuberous scle-rosis) no speciﬁ  c biological markers for autism have yet been found 
although some promising leads for early screening or children at risk (i.e. siblings) have appeared. It is likely that early diagnosis may change dramatically in the not so distant future as potential susceptibility genes are identiﬁ  ed or are combined with innovative 
approaches to screening—this will have potentially major impor-tance since there is some suggestion that early intervention may signiﬁ  cantly improve outcome.
www.autism.fm. Regularly updated website with links to other sites.
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Jacobson, J.W., Foxx, R.M., and Mulick, J.A. (2005). Controversial therapies

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1643
9.2.4 Attention deﬁ  cit and 
hyperkinetic disorders in childhood and adolescence
The concept of ADHD arose from neurological formulations, but 
does not entail them, and the modern deﬁ  nition simply describes a 
set of behavioural traits. The historical evolution of the concept was described by Schachar.
(1) It began with the idea that some 
behavioural problems in children arose, not from social and famil-ial adversity, but from subtle changes in brain development. The term ‘minimal brain dysfunction (MBD)’ was often applied, and covered not only disorganized and disruptive behaviour but other developmental problems (such as dyspraxias and language delays) presumed to have an unknown physical cause. MBD, however, stopped being a useful description when studies of children with deﬁ nite and more-than-minimal brain damage made it plain that

they showed a very wide range of psychological impairment, not a characteristic pattern (see Harris, this volume); and therefore it was invalid to infer the presence of brain disorder from the nature of the psychological presentation.
The successor to the concept of MBD was attention deﬁ  cit and 
hyperactivity: deﬁ  ned, observable behaviour traits without assump-
tion of cause. ‘Attention Deﬁ  cit/Hyperactivity Disorder’ (ADHD) 
in DSM-IV , and ‘Hyperkinetic Disorder’ in ICD-10, describe a constellation of overactivity, impulsivity  and inattentiveness . These 
core problems often coexist with other difﬁ  culties of learning,

core problems often coexist with other difﬁ  culties of learning, 
behaviour or mental life, and the coexistent problems may domi-nate the presentation. This coexistence, to the psychopathologist, emphasizes the multifaceted nature of the disorder; to the sociolo-gist, a doubt about whether it should be seen as a disorder at all; to the developmentalist, the shifting and context-dependent nature of childhood traits. For clinicians, ADHD symptoms usually need to be disentangled from a complex web of problems. It is worth-while to do so because of the strong developmental impact of ADHD and the existence of effective treatments. Public controversy continues, but professional practice in most countries makes ADHD one of the most commonly diagnosed problems of child mental health.
Overactivity

The idea of overactivity refers simply to an excess of movement. It is not totally dependent on context and cannot be reduced to non-compliance: physical measures of activity level have indicated that it is higher in children with ADHD than in controls, even during sleep.
(2) It is, however, partly dependent upon context: it is 
often inhibited by a novel environment, creating a pitfall for the inexperienced diagnostician who may exclude it incorrectly because it is not manifested during observation at a ﬁ  rst clinic visit. It may 
not be evident in situations where high activity is expected, such as the games ﬁ  eld. The key situations where it is evident are familiar 9.2.4 attention deficit and hyperkinetic disorders in childhood and adolescence
to the child and where calm is expected, such as visiting family 
friends, attending church, mealtimes, homework and—often the most troublesome—at school, during class.
(a) Impulsivenes

Impulsiveness means action without reﬂ  ection—often described as 
a failure to ‘stop and think’ . The term covers premature, unprepared and poorly timed behaviours—such as interrupting others, and giving too little time to appreciate what is involved in a school task or a social situation.
(b) Inattentiveness
Inattentiveness means disorganized and forgetful behaviour: short-sequence activities, changing before they are completed, with a lack of attention to detail and a failure to correct mistakes. All these are behavioural observations, not psychological constructs. At a cognitive level, ‘Attention deﬁ  cit’ is a rather poor descriptor;

the performance of affected children does not fade with time on a task any more than that of ordinary people and the presence of irrelevant information (‘distractors’) does not worsen their performance disproportionately to that of other people.
(3) There 
are cognitive changes of a different kind (see ‘Aetiology’ below); but the diagnosis of inattentiveness depends on descriptions and obser-vations of behaviour rather than on tests of performance.
Many other behavioural changes characterize some children with 
ADHD. They are, for instance, often irritable and their emotions can ﬂ  ash very rapidly when provoked. They may sleep badly (and 
this in turn can contribute to poor concentration). They can be aggressive to other people and non-compliant to authority. They can also be charming, humourous, inquisitive and intuitive. None of these, however, are either constant in ADHD or conﬁ  ned to those 
with ADHD. They are worth noting, but they do not make the diagnosis.

Attention Deﬁ  cit/Hyperactivity Disorder in DSM-IV is deﬁ  ned 
as the presence of a number, above a cut-off, of behaviours consid-ered to reﬂ  ect the cardinal features described above to a degree that 
is developmentally inappropriate and gives rise to some impairment in more than one setting (e.g. school and home).
(4) Overactive and 
impulsive behaviours are considered together as a single construct of ‘hyperactivity-impulsiveness’ , and for convenience the combined dimension will be referred to in this chapter as ‘hyperactivity’ . Examples of inattentive behaviour are added together and form a separate dimension. There are therefore three subtypes: hyperactive-impulsive, inattentive and combined.
The same problems characterize the ICD-10 definition of 
‘Hyperkinetic Disorder’ (HD),
(5) but with added requirements:

(5) but with added requirements: 
especially, that all three cardinal features are present, pervasively across home, school and other situations. HD is therefore, in effect, a subtype of ADHD.
(6, 7) The subtypes of hyperkinetic disorder are 
based on the presence or absence of conduct disorder—and indeed the presence of conduct disorder is an important factor with which to reckon in the course.
Diagnosis
Description of the symptoms makes them sound easy to recognize, and indeed the problems are usually very salient, disruptive to

SECTION 9  child and adolescent psychiatry 1644
other people, and common causes of referral to health and special 
education services. Nevertheless, there are pitfalls in the diagnosis, making it necessary for a specialist assessment to be undertaken before the diagnosis is given.
Ambiguous criteria
The behavioural problems, described in outline above, are trans-lated into detailed criteria in DSM-IV and ICD-10, and some of them can be ambiguous. For example, ‘does not follow instructions’ is a DSM item intended to imply that instructions are forgotten or not attended to; but the behaviour can also be shown for reasons of wilfulness and therefore a part of oppositional/deﬁ  ant disorder. 
Careful description or witnessing the behaviours complained of is necessary.
Confusion of cardinal and associated features

Many behavioural problems—such as temper tantrums, sleepless-ness, aggression and disobedience to adult authority—are common in children with ADHD, and may be the key reasons for presentation. It is easy to make the mistake of diagnosing ADHD when only disruptive behaviour is present. Much of the confusion comes from the way impulsiveness is operationalized in the diagnostic schemes. Behaviours, such as calling out in class and interrupting others, can indeed come from a difﬁ  culty in holding oneself back; but they 
can also represent deliberate ﬂ  outing of the rules, and in a London 
survey of 6- to 8-year-old boys they were as common in non-hyperactive but deﬁ  ant children as in the hyperactive.
(8) Direct

(8) Direct 
observation can usually make the distinction—watching either the children tackling tasks requiring them to stop and think in the clinic, or their natural behaviour in the classroom. Inattentive behaviour also helps to make the diagnosis of ADHD and is less confounded by oppositionality.
(a) Reliance on non-expert judgements

The behaviours of ADHD are continuously distributed in the population (see ‘Epidemiology’). The level that is considered normal or acceptable will vary from one culture to another and from one rater to another. T o be diagnosed, they should be exces-sive not only for the child’s age but also for the developmental level; and this demands considerable familiarity with the usual range of variation. The diagnostician will acquire this in the course of training and experience; experienced teachers will be excellent judges; but inexperienced or overstressed parents may identify the problems at a low level of hyperactive behaviour, or suppose that an abnormal level is only to be expected in childhood. It is usually helpful to obtain a detailed behavioural account rather than rely on an overall judgment of ‘overactivity’ or ‘failure to concentrate’ . Contradiction between sources may occur, and leads to arguments

between parents and teachers. This may be due to different expec-
tations, the emotional relationship of raters with the child, or children behaving very differently in contexts that vary in the demands placed on the children. The clinician needs to understand the full context of the way involved adults describe the child.
(b)  Problems of recognition in the presence of coexistent 
problems
It is commonplace for children whose problems meet the criteria 
for ADHD to show other patterns of disturbance as well. This is often, confusingly, called ‘comorbidity’ – confusing because it assumes that the other pattern is a distinct disorder, which is only

for ADHD to show other patterns of disturbance as well. This is often, confusingly, called ‘comorbidity’ – confusing because it assumes that the other pattern is a distinct disorder, which is only 
one of the explanations for coexistent problems. Clinicians need to understand the relationships for two reasons; so that they do not make or miss the diagnosis of ADHD; and so that they can make good strategies for treating ADHD in the presence of other disor-ders and other disorders in the presence of ADHD (see ‘Treating Complex cases’ , below).
(c) Conduct and oppositional disorders
The commonest association and the best researched is with conduct and oppositional disorders. Nearly half the children with hyperac-tive behaviour in a community survey showed high levels of deﬁ  ant 
and aggressive conduct as well; but the associations of the two problems were different, with hyperactivity (but not conduct problems) being associated with delays in motor and language development.

(8) Genetic research indicates higher heritability 
for hyperactivity than for deﬁ  ant and aggressive behaviour; but 
there are some genetic inﬂ  uences that are common to both.(9)
Hyperactivity is more responsive to stimulant medication than are 
less hyperactive forms of conduct problem.(10)
 When both ADHD and conduct problems are present, then the 
combined diagnosis (‘hyperkinetic conduct disorder’ in ICD-10) shows the associations of both disorders. ADHD is therefore not to be diagnosed by the absence of conduct disorder features, but by the clear presence of the core problems of inattentivess and disorganization.
(d) Tourette disorder and multiple tics

A different kind of differential is presented by children with T ourette disorder. Their motor restlessness may indeed represent the coexistence of ADHD, but can result directly from tics. If a child’s tics are very frequent and there are a large number of them, then their repetitive and stereotyped nature may not be apparent and they may be seen simply as restless ﬁ  dgetiness. Again, direct 
observation of the pattern of overactivity is the key. When there is doubt, videorecording the child and subsequent slow-motion review may make repetitive patterns evident.
(e) Autism spectrum disorders

Children with autism have clear and characteristic impairments of language, communication, and social development. Spectrum disorders, however, can raise diagnostic challenges. Children with ADHD alone often show language delays (usually of an expressive nature with over-simple utterances, by contrast with the receptive difﬁ culties and idiosyncratic patterns of autism). Their attention 
difﬁ culties may make them unresponsive to the overtures of others 
in a way that can simulate the social obliviousness of people in the 
spectrum of autism, and they are often friendless—not because of 
lack of interest in others but because of the capacity of hyperactive 
behaviour to irritate other people. Indeed, attention problems can

behaviour to irritate other people. Indeed, attention problems can 
extend to perseverativeness on certain activities such as video games that may be mistaken for the restricted interests of autism. All these factors can lead to ADHD being mistaken for autism, but the reverse can happen too. There are other reasons for overactive behaviour in autism. First, stereotyped patterns of driven overac-tivity can be seen: they are not disorganized or impulsive and are often made worse by change and novelty (which usually reduce the overactivity of ADHD). Second, episodic bursts of extreme activity can be seen and may be best regarded and treated as catatonic. Third, akithisia may result from neuroleptic medication, or  irritable

1645
restlessness from anticonvulsants, and it will be necessary to estab-
lish a clear history that ADHD has been a persistent trait.
(f) Attachment disorders
Reactive attachment disorder (RAD) may share with ADHD a disinhibited style of relating to other people (an unreserved but shallow making of social contact). Children with RAD, however, tend to be controlling rather than disorganized, and vigilant rather than inattentive; and inattention and impulsiveness are not cardi-nal features of RAD; so it is not difﬁ  cult to recognize both patterns

when present in an individual child. The confusion in practice often comes from theoretical misconceptions. Those caring for neglected or abandoned children may consider that the diagnosis of ADHD cannot be accurate because the cause of the children’s problems is clearly to be found in their early deprivation. The causal pathway may indeed be that of neglect (though genetic inheritance and fetal exposure to toxins also need considering); but ADHD is a descriptive category, not an explanatory one. If the 
pattern of ADHD is present it still needs recognizing—not least 
because the cause of the ADHD behaviour does not seem to deter-mine the response to stimulant medication, and children who have encountered neglect or abnormal early attachment may still have their ADHD problems reduced by medication.
(10)
(g) Bipolar disorders

(10)
Both ADHD and manic conditions are characterized by overactivity, overtalkativeness, a sensation of whirling thoughts, and often by irritable mood. The distinction is made by the presence in bipolar disorder of episodicity, euphoria, and grandiosity. A suggestion that these distinguishing features are not in fact present in child-hood bipolar disorder has naturally led to great overlap between the expanded childhood bipolar diagnosis and ADHD with poor emotional regulation, and further research will be needed to clarify whether there is a distinction.
In all these differential diagnoses, the principle is to establish that 
the child shows not only overactive behaviour, but the speciﬁ  c 
pattern of ADHD. Experienced judgement may be required, and the practice of diagnosing on the basis of questionnaire scores alone risks overidentiﬁ  cation.
In adult life, there are still more possibilities for misdiagnosis.

In adult life, there are still more possibilities for misdiagnosis. 
The commonest reasons for uncertainty are in distinguishing from atypical bipolar disorder and the effects of substance misuse. ‘Personality disorder’ is sometimes applied; and indeed ADHD shares with personality disorders a long-standing trait quality, but can also be a more precise way of describing the difﬁ  culties 
presented. Differentiation from the normal range of variation can be difﬁ  cult in the absence of clear standards. The task of the diag-
nostician is harder when adults are presenting for the ﬁ  rst time if 
only self-report is available; the self-description of hyperactivity may be a form of self-depreciation.
Methods of recognition
(a) Rating scales and informant interviews

Questionnaire ratings by parents or teachers are very useful for screening purposes, and in group studies they give a fairly good discrimination between people with a clinical diagnosis of ADHD and controls from the ordinary population.
(11) Many are 
available(12,13) and the most famous are those from Conners, which 
yield several different scoring systems; and derivatives such as the Iowa Conners, the SWAN and SNAP scales.(14) They do however 
leave a fair number of individuals misclassiﬁ  ed, and are not suit-
able as the sole means of establishing a diagnosis. A detailed inter-view with parents establishes what actual behaviours are the basis for ratings, allows professional judgement to be included, and remains the most informative single method.
(b) Psychiatric interview

Interview with the child is valuable for the observation of attention and social interaction that it yields, and for understanding a child’s view of their predicament. Children, however, are not good witnesses about their own concentration and impulse control, and even affected adults are not good at describing themselves in these terms. The experience of ADHD is usually one of suffering the reactions evoked from other people, or an experience of repeated failure. Adults often describe an experience of whirling and inter-rupted thoughts (in the absence of manic features); and some children will say the same, especially if treatment has enabled them to make a comparison with another way of being.
(c) Investigating underlying causes

Assessment needs not only to distinguish ADHD from related disorders, but to consider whether the ADHD pattern may result from remediable causes. The anamnestic history is by far the most productive investigation. It should include whether hearing prob-lems have been excluded by previous testing (and, if not, an expert assessment should be arranged), and any injuries or diseases are potentially damaging the brain. The strengths and weaknesses of the family environment need to be assessed; they may dictate the choices of treatment. Physical examination should be sufﬁ  cient to 
detect congenital anomalies, skin lesions, and motor abnormalities that can be the pointers to a neurological cause. Psychometric assessment is desirable whenever there are problems at school, both to generate an idea of developmental level against which the ‘developmental inappropriateness’ of behavioural symptoms can

be judged, and to detect barriers to learning that may be the reason 
for inattentiveness. Special physical investigations are not routinely necessary. EEG often yields evidence of immaturity, but this does not advance assessment much and is not routinely indicated. It is valuable in the investigation of epilepsy and in the rare cases when deterioration of function suggests the possibility of a degenerative disorder. Blood tests should be planned only on the basis of history and examination, but may include tests of thyroid function, lead (in high-lead areas) chromosomal integrity (including fragile-X probe) when there is other evidence of developmental delay, and speciﬁ  c DNA tests when there is clinical suspicion of a phenotype 
such as that of Williams syndrome.
Prevalence estimates vary widely; but most of the variation between studies comes from differences in definition
(6) A community

(6) A community 
survey in London of more than 2000 6–8-year-old boys found a continuum of severity on rating scales: at each successively higher level of hyperactive behaviour there were successively fewer num-ber of children
(8) The genetic evidence also supports a continuum: 
in a population-based twin study, the inﬂ  uences on hyperactive 
behaviour were similar over the whole range of variation.(15)
Estimates of prevalence are therefore critically dependent upon the cut-off point chosen.9.2.4 attention deficit and hyperkinetic disorders in childhood and adolescence

SECTION 9  child and adolescent psychiatry 1646
Two major inﬂ  uences on the cut-off are the diagnostic criteria 
applied and the cultural attitudes of raters. Attention Deﬁ  cit/ 
Hyperactivity Disorder has a rate in the school age population usu-ally given at about 5 per cent, but varies from 2.4 to 9 per cent
(6, 16)
probably depending on how rigorously ‘impairment’ is deﬁ  ned. 
The ICD-10 diagnosis of Hyperkinetic disorder yields rates around 1 to 2 per cent of the school age population.
(6, 17) Sex differences 
are marked: population surveys suggest that 2–3 boys are affected for every girl.
(18)
The frequency of hyperactive behaviour in the population, at 
least as indexed by rating scales in surveys, has not been increasing over the last two decades.
(19) By contrast, there have been large

(19) By contrast, there have been large 
increases in the frequency with which hyperactivity as a medical condition has in practice been recognized—most obviously evidenced by a great increase in the rates of stimulant prescription between 1995 and 2005 in the UK (Wong et al, in submission) and 
a continuing increase in the USA.
(20) The studies suggest that 
stimulant medication is given for about 3 children per 1000 in the UK (i.e. about 12 per cent of those in the community meeting ADHD criteria with impairment) and about 40 per 1000 in the USA. It is likely that health service organization plays a part in determining recognition. In the USA survey, a diagnosis of ADHD was more likely to have been made for children whose families Carried Health Insurance.
(20) In a UK survey, children with high

(20) In a UK survey, children with high 
hyperactivity as rated by teachers and parents seldom received a diagnosis, with the main ﬁ  lter coming at the level of recognition 
by primary health care services.
(21)
In adult life, those who were hyperactive as children still have an 
elevated rate of hyperactivity and related social impairment (reviewed systematically by Faraone et al .).
(22) Indeed, a cross-
sectional population survey of adults described a surprisingly high prevalence rate of about 4 per cent, with a high rate of co-existent psychological morbidity.
(23) More evidence is needed 
on the extent of the adult problem. It is however clear that a sub-stantial number of adults, who were not diagnosed in childhood, may be affected, and an increasing number are presenting for the ﬁ rst time to adult services.
Aetiology
Genetic inheritance
Genetic inﬂ  uences are strong: Twin studies suggest a heritability

Aetiology
Genetic inﬂ  uences are strong: Twin studies suggest a heritability 
around 80 per cent, making it one of the psychological disorders most strongly inﬂ  uenced by genetic inheritance,
(24, 25)  and adoptive 
family studies concur in emphasizing the strength of association with biological relatives.
(26) Indeed, several DNA variants in genes 
coding for relevant proteins have now been identified and replicated.
(27) In particular, the genes coding for the dopamine D4 
and D5 receptors, the dopamine transporter, SNAP25 (affecting synaptosomal protein), the serotonin 1b receptor and the serotonin transporter have all been associated with ADHD by more than one group of investigators. Several kinds of caution are, however, needed in interpreting these ﬁ  ndings. The odds ratios are all quite 
small (between 1.1 and 1.5), no polymorphism so far found is either necessary or sufﬁ  cient; it is possible that there are subtypes

small (between 1.1 and 1.5), no polymorphism so far found is either necessary or sufﬁ  cient; it is possible that there are subtypes 
of ADHD with different genetic inﬂ  uences
(28)
Current research continues to seek more associated genes, 
especially by genome scans and positional cloning and to empha-size the likely importance of gene-environment interactions. Individual studies have reported that the risk alleles for genes in the 
dopamine system magnify the effects on the foetus of maternal smoking and alcohol consumption during pregnancy,
(29, 30) and 
catechol o-methyl transferase (COMT) of low birth weight(31)
Environment
Environmental influences are reviewed by Taylor & Warner 
Rogers.(32) There are associations with several kinds of adversity in 
fetal and early postnatal life; and genetic factors may inﬂ  uence the

fetal and early postnatal life; and genetic factors may inﬂ  uence the 
exposure to some hazards (e.g. to lead, via playing in contaminated areas) as well as their impact. Many of the insults have generalized effects on brain development and can also lead to low IQ.
Prenatal
The prenatal factors implicated include smoking and drinking in pregnancy,
(33) cocaine,(34) maternal stress during pregnancy,(35)
anticonvulsant use(36) and the factors causing very low birth 
weight.(37) For some of these, there is experimental evidence for 
a harmful effect in animals. Smoking, for example, has high bio-logical plausibility: the substances inhaled have an effect in animal models, and there is a dose-response relationship in human studies.
(38) It is important to recognize these risk factors in assessing

(38) It is important to recognize these risk factors in assessing 
a referred child, because one may be able to prevent a subsequent child from suffering the same injury. Interpretation of a positive history, however, is not straightforward, because of the likely effects of genetic inﬂ  uences as well. There is no doubt of the existence of 
the fetal alcohol syndrome, nor that it can include ADHD symp-toms, but the effect of lesser degrees of exposure is uncertain. Apparent associations could be magniﬁ  ed by gene-environment 
correlations. Maternal drinking may be inﬂ  uenced by the same 
genes that inﬂ  uence ADHD; the genes and the pregnancy toxin 
may be handed down together. Knopic et al .
(39) investigated this 
by studying the offspring of mothers who were identical twins yet differed in whether they had a history of alcohol abuse: ADHD was common in both groups: the suggestion was that the genes were 
more important than the presumed exposure to alcohol.
Postnatal

Postnatal
In postnatal life, the best deﬁ  ned risks are at extreme levels of mis-
fortune. Head injury and brain disease have to be severe before they have a causative effect; minor injury is often a result of hyper-activity rather than a cause.
(32) Children who experienced extreme 
deprivation in the orphanages of Romania showed increased rates of pervasive and persistent overactivity and inattention in later childhood, even though they had been adopted into English fami-lies before the age of 4 years.
(40) Minor degrees of psychological 
adversity have not been shown to cause ADHD (though they may well be associated with coexistent conduct disorder). Indeed, the twin studies that show genetic inﬂ  uences can also be used to distin-

guish between the environment that all children in the family share (such as a chaotic family life style or the use of television), and the environmental inﬂ  uences that affect one child but not another; 
only the latter play a part.
Diet is often blamed for hyperactivity. There is some truth in it, 
but the effects seem to be modest. The main evidence comes from therapeutic trials (see under ‘Treatment’) which indicate that a range of foodstuffs can be harmful for individual children – includingcow’s milk, wheat ﬂ  our, eggs, and artiﬁ  cial colourings and additives. 
Individual idiosyncrasies seem more important than a damaging

1647
effect of the substances on everyone. Experimental trial, however, 
giving colourings including tartrazine to an unselected population of preschool children, suggests that the substances have a small but measurable adverse effect on behaviour across the whole range and so ought to be seen as mildly toxic.
(41)
The effect of these aetiological inﬂ  uences on the developing brain 
is being clariﬁ  ed by the neuroimaging possibilities being created by 
magnetic resonance and other non-invasive techniques. Several brain areas are smaller in ADHD than controls.
(42) The difference 
persists through adolescence into adult life and is more marked in those who have never received medication than those who have. The areas most affected—frontal, striatal and cerebellar—are involved in self-organizational abilities that fail in those with ADHD.
At a neuropsychological level, there have been extensive

At a neuropsychological level, there have been extensive 
comparisons between young people referred for, and diagnosed with ADHD in the USA and age-matched controls without psycho-pathology. ‘Executive function’—which has become a broad and ill-defined term for psychological processes by which people modify their responsiveness to stimuli or the organization of their responses—has received special attention and is reviewed by Willcutt et al.
(43) In general summary, many such functions show 
signiﬁ  cant differences between ADHD and controls, but the effect 
sizes are modest and do not suggest that research has yet hit on either a fundamental deﬁ  cit or on a means of diagnosis to replace 
behavioural description.
Motor inhibition and cognitive inhibition have received particu-
lar attention, deriving from the behavioural observation that children with ADHD can be described as ‘disinhibited’ , and from an inﬂ  uential suggestion by Barkley
(44) that failures of inhibitory

(44) that failures of inhibitory 
process could underlie the other cognitive deﬁ  cits – such as inefﬁ  -
cient planning ahead, and poor self-control by internal language. There is not much doubt that experiments reliably produce poor performance in ADHD on tests of suppressing motor responses.
(45)
Indeed, functional neuroimaging has found that people with ADHD, as a group, show less activation of brain structures involved in response suppression, even when they are performing at a satis-factory level on a simple test.
(46) There is more uncertainty about 
whether this form of impulsiveness does indeed derive from deﬁ cits in inhibition or from other kinds of psychological alteration,

whether this form of impulsiveness does indeed derive from deﬁ cits in inhibition or from other kinds of psychological alteration, 
such as reluctance to put effort into planning responses of any kind, or to be patient during a period of waiting. This last idea, ‘delay aversion’ , has been elaborated and tested
(47) and suggests that some 
children with hyperactive behaviour are still capable of delaying a response when appropriate provided that the length of time they have to wait for the reward is controlled. A head-to-head com-parison of inhibition failure action (in a ‘stop’ test) and delay aver-sion (in a test of delaying gratiﬁ  cation) has been carried out, with 
the result that either test on its own produced a moderate distinc-tion between ADHD and controls, but combining the two resulted in a much better discrimination, with sensitivity and speciﬁ  city 
around 80 per cent.
(48)

(48)
The clinical applicability of the extensive research investment in 
psychological testing is rather small. The tests have for the most part lacked either standardization or establishment of test–retest reliability; the interpretation of an individual child’s score, accord-ingly, lacks quantitative support. There are a few tests of related abilities that have normative values with age standardization
(e.g. the T ests of Everyday Attention for Children: TEACH). Their place in practice is not to make a diagnosis of ADHD, but to sug-gest which of several possible cognitive weaknesses apply in the individual child. In principle, useful advice for education could fol-low from such testing; but evaluations—of the uptake by teachers, of the advice or the impact on the child—are lacking.
First 3 years
A ‘difﬁ  cult temperament’ in early childhood includes overactivity

A ‘difﬁ  cult temperament’ in early childhood includes overactivity 
and poor self-regulation, and can have a harmful effect on parent–child relationships; but the concept of inattentiveness is hard to apply at this age and the diagnosis would be insecure.
Age 3–6
ADHD behaviours are clearly recognizable by this age, and there is a strong likelihood of persistence into the school years.
(49) Parent 
training is an effective intervention (see ‘Treatment’) and should be available for parents with children at risk, without waiting for formal diagnosis.
Age 7–11
 School and peer demands make ADHD behaviours impairing; the tolerance of families and the culture at large help to determine whether ADHD is seen as a problem; and this is a very common age for referral and diagnosis. Hyperactivity (as opposed to inattentive-ness alone) becomes important in gene rating aggressive and antiso-
cial behaviour and delinquency.
(50) The extent to which there is a

(50) The extent to which there is a 
poor social outcome may depend upon genetic inﬂ  uences,(51, 52) on 
environmental inﬂ  uences such as a hostile home atmosphere,(53)
and on gene–environment interactions (a COMT gene polymor-
phism together with a low birth weight predicted the development of antisocial symptoms in those with ADHD).
(31)
Age 12–18
During adolescence, there is a maturing in the abilities of self-control, and some children with ADHD will lose their problems; but the demands for self-control rise as well, and so the children are still more impulsive and inattentive than their peers and four times as likely to merit a psychiatric diagnosis.
(54) Indeed, about half 
of cases diagnosed in childhood will retain the full diagnosis in adolescence.
(55)
Those who continue to show hyperactivity are at risk for 
other problems, notably ag gressive and antisocial behaviour and 
delinquency,(50) and motor trafﬁ  c accidents.(56)
Adult life

(55)
Adult life
By adult life, most will no longer meet full diagnostic criteria for 
ADHD; but, equally, most will retain some functional impairment related to hyperactivity.
(22) This should imply a falling prevalence, 
but survey of adults has found high rates (about 4 per cent).(23)
Some part of this discrepancy may derive from adults developing impairment for the ﬁ  rst time; they may have had ADHD symptoms 
as children, but the symptoms were not impairing, and have only become impairing when adult life imposes responsibility and high expectations.9.2.4 attention deficit and hyperkinetic disorders in childhood and adolescence

SECTION 9  child and adolescent psychiatry 1648
The implications for practice are that from childhood to early 
adult life, and perhaps longer, severe levels of hyperactivity and inattentiveness should be seen as potentially chronic disability; and that intervention should not target only the core symptoms but also the surrounding tangle of adverse personal relationships and educational failure.
Treatment evaluations
There have been many trials of central nervous stimulants (espe-cially methylphenidate, with some work on dexamfetamine and pemoline) and atomoxetine. A systematic review was undertaken by NICE (National Institute for Clinical Excellence).
(57) Sixty-ﬁ  ve

(57) Sixty-ﬁ  ve 
trials met quality criteria and were assessed. Quantitative review indicated heterogeneity among the trials, so a meta-analysis was not attempted; but there was no doubt about the superiority of methylphenidate, atomoxetine, and dexamfetamine to placebo. Economic analyses were undertaken and were not very robust, but suggested that all three gave acceptable cost per Quality-Adjusted Life Y ear. All three should be in clinical use, with the decision regarding which product to use to be based on comorbidity, adverse effects, compliance, potential for drug diversion, and individual preferences with differences in cost as a secondary consideration.
Several proprietary preparations of methylphenidate have 
appeared that offer an extended release through the day; they differ in the physics of their delivery systems and therefore in their 
speed of onset and duration of action. Banaschewski et al.
(58) made

(58) made 
a systematic review of trials on them and on atomoxetine, which also has a sustained effect through the day. They indicated that the effect size of extended-release methylphenidate preparations was comparable to that of immediate-release—around 0.8–1.1 SD; but, not surprisingly, the effect of an 8-hour preparation was somewhat smaller than that of a 12 preparation on parent ratings, though similar on teachers’ ratings of child behaviour. The effect size of atomoxetine was around 0.6 SD.
Most studies have been carried out on children and adolescents 
of school age. In children under 6 years, the limited trial evidence suggests that stimulants are more effective than placebo in reduc-ing hyperactivity and the level of stress in family relationships
(59)

(59)
The safety of the drugs in this age group is uncertain. For adults, enough randomized controlled trials have appeared for stimulants and atomoxetine that meta-analysis has been possible, with the conclusion that they are more effective than placebo.
(58, 60)
Psychological evaluations
Behaviour therapy has received several trials, but no satisfactory systematic review has yet appeared. Miller et al.
(61) attempted one, 
but decided to exclude most of the trials because they did not meet the quality criteria that were imposed. Nevertheless, reasonably good effect sizes have been reported in randomized trials compari-sons for the comparisons of behaviour modiﬁ  cation programmes 
(usually delivered on an individual family basis) with no treatment or treatment as usual.
(62, 63) Group programs of parent training— 
which typically include supportive education in behavioural man-agement—are also effective, perhaps particularly for preschool children.

(64, 65) Cognitive therapy, by contrast, has been disappoint-
ing in trials.(66)Elimination diets
Several trials of eliminating foods that seem to be incriminated for an individual child, followed by double-blind administration of those foods in experimental design, have found that the identiﬁ  ed 
foods can worsen that child’s behaviour more than a placebo.
(67)
The implication, as for food effects on disorders such as eczema, is of idiosyncratic intolerances so that each child needs investigating individually. This is troublesome for families, and perhaps only applicable to younger children whose diet is still under parental control.
Drug vs. psychosocial intervention

There has been controversy over the relative merits of medication and behaviour therapy. In the USA, the debate has been sharpened by a perceived over-prescription of drugs and led to a large-scale random-allocation non-blind trial.
(68) The trial compared rather

idealized versions of: medication (with very careful and systematic monitoring of dose and response), behaviourally oriented psycho-social therapy (delivered with high intensity and a combination of approaches to teachers, parents and the young people themselves), both interventions given together, and a ‘treatment as usual’ policy of referring back to community agencies (which usually resulted in medication). At the prime outcome point—14 months after randomization—the outcome for those given the research style of medication was better than those given behavioural treatment only and considerably better than those given treatment as usual, even when that included medication. Adding medication to behaviour therapy improved the outcome for the primary measures of hyperactive behaviour; adding behaviour therapy to medication did not—but did yield better control of aggression at home, improvement in the overall sense of satisfaction of parents, lower medication dosage, and a higher rate

behaviour therapy to medication did not—but did yield better control of aggression at home, improvement in the overall sense of satisfaction of parents, lower medication dosage, and a higher rate of very good outcomes. These improvements in the combination treatment were real, but very expensive to achieve, and it remains uncertain whether such beneﬁ  ts could be matched by behaviour therapy delivered under

the constraints of ordinary practice. The marked superiority of careful medication to other forms of intervention did not persist at later follow-up points. At 2 and 3 years after the start of the trial, those who had been allocated to all arms of the trial showed rather similar outcomes. None were untreated, and all groups showed less hyperactivity than at the beginning of the trial, so the ﬁ  nding 
should not lead to therapeutic nihilism. The likely reasons for the waning of the medication effect are that the drug loses its effect, stops being taken, or depends upon careful and skilled adjustment of dosage in the longer term.
Psychoeducation

Unlike most psychiatric conditions, a diagnosis of ADHD is often sought by parents and welcomed by them. The image, of being a physically caused neurological disease, is often perceived as a relief from the stigma of mental disorder. On the other hand, the media controversy over whether it is a ‘real’ disorder, and over the use of controlled drugs, leaves some parents confused and fearful.
Assessment on the principles above will have led to an individual 
formulation of the nature and causes of the impairment. Extended explanation is worthwhile in the longer term. An over-simple

1649
description in terms of a chemical deﬁ  ciency in the brain may seem 
a useful starting point but can lead to unrealistic expectations for treatment and frustration with the doctor or, worse, with the child. A model of chronic disability is in keeping with the evidence from longitudinal studies; but needs to be modulated by the good out-come for some children, the improvement for most, and the ability of warm and encouraging parenting to reduce the risks of antiso-cial behaviour in later childhood and adolescence.
(53)
Children’s understanding of their problems is also worth a good 
deal of effort. Little research has so far addressed the issue, but it is important to their ability to cope. They need to know that their problem is understood, that treatments are available, that they can inﬂ uence their outcome by their own actions, and that the people

around them understand all this and can be encouraging. Positive role models are useful: some successful sports stars, performers, politicians and business people have outed themselves as having, and sometimes using, ADHD. Explanations need to be repeated as the young people mature and expect a fuller and more interactive discussion.
Explanation is often needed by teachers as well. They may need 
to revise their expectations of the level of challenge with which the child can cope; and for some frustration can lead to antagonism 
towards the child’s family. If they already see ADHD as a neuro-
logical disease, then the frequent observations of changeability in the children, and of ability to cope sometimes with difﬁ  cult tasks,

logical disease, then the frequent observations of changeability in the children, and of ability to cope sometimes with difﬁ  cult tasks, 
may make them reject a neurological cause—and with it the diag-nosis and the validity of drug treatment. They may need to know that physical and psychological factors can both enter into the child’s presentation and that the effect of medication does not depend on the aetiology.
(10)
After explanation comes basic advice on helping the children’s 
development. The ﬁ  rst steps with parents are to establish whether 
there is already a framework of frequent warm interactions and effective ways of giving instructions and following up children’s actions with consistent patterns of reward or loss of reward. If this does not already exist, then a parent training group is often helpful. Both a supportive atmosphere and the teaching of skills in behav-iour modiﬁ  cation seem to be necessary. The target behaviours for

modiﬁ  cation are often the ones most troublesome to parents— 
disobedience and aggression—rather than restlessness or inatten-tiveness speciﬁ  cally.
Liaison with schools should include advice on the severity of the 
problem and the intensity and nature of extra help that will be required. T eachers will often be able to share good practice in class-room management. One of the principles is to maintain good stimulus control, for instance by having the affected child at the front of the class under the teacher’s eye. Another is to ﬁ  nd oppor-
tunities for the children to let off physical energy (they can some-times be used as messengers between classrooms) and to learn in short chunks. Variety and interest in the material to be learned or understood is useful. Transitions between activities in the class-
room are often the time for children to become disorganized, and the child with ADHD should be the ﬁ  rst to change activity with

room are often the time for children to become disorganized, and the child with ADHD should be the ﬁ  rst to change activity with 
the teacher’s supervision. Individual attention is probably the most effective resource in the classroom, but it is also very demanding: a classroom assistant may help to achieve it. Star charts for younger children and token economy systems for older ones are often recommended, but usually depend upon the system used for the rest of the class.Speciﬁ  c interventions
When straightforward advice is not enough, then the two best-
evaluated treatment approaches are behaviour modiﬁ  cation  and 
medication management . The choice of which to start with will 
depend on several conclusions from the assessment: the severity of the problem (with more severe problems responding preferentially to medication rather than behaviour therapy
(7) the availability of

(7) the availability of 
treatment; the willingness and ability of parents (or teachers) to engage in psychological intervention; the urgency of the problem (with medication affording a more rapid change); and the wishes of the family. Whichever approach is taken ﬁ  rst, the other should be 
available without undue delay if the response is below expectation.
(a) Behaviour modiﬁ  cation
The principles of behaviour modiﬁ  cation do not differ from those 
used in other kinds of behaviour problem (e.g. 62). Target behav-iours should be clearly speciﬁ  ed and monitored; the antecedents and 
consequences of the behaviours should be understood and modiﬁ  ed 
as appropriate; clear schemes of reward and punishment should be established, understood by the child, and applied consistently. There are, in addition, some modiﬁ  cations to suggest for the speciﬁ  c

needs that come from the nature of ADHD. The rapid delay-of-reward gradient calls for contingencies to be applied with particular attention to speed. For example, a kitchen timer can be set for an appropriate length of activity depending upon the individual child (for instance, 5 min application to homework, or 30 min spent free of aggression to siblings). When the timer sounds, an obvious reward (such as a token) is given within a very few seconds. The reward may 
swiftly lose its reinforcing quality with repetition, so frequent changes 
in the reward (or the backup to a token) are needed. Impairment in error correction may make it all the more necessary to be explicit and swift in explaining to the child which of their behaviours has earned the reward, or its loss. Response cost (such as loss of tokens) is usually advocated in conjunction with the reward scheme.
(b) Medication
Prescription of medicines can be guided by published schemes(e.g.

13). Specialist assessment is highly desirable when problems are 
at the level that warrants medication—not because the treatment is specially risky, but because it is important that remediable causes and associated conditions are not overlooked. The ﬁ  rst choice of 
medicine is usually methylphenidate. If immediate-release is cho-sen, then one usually begins with doses, three times a day about 5 mg to 10 mg, depending on the child’s weight. If there are no adverse effects, then the dose is increased upwards (probably weekly) until there is a good response, or adverse effects become troublesome, or the ceiling of 0.7 mg/kg/dose is reached—whichever comes ﬁ  rst. If an extended-release preparation is chosen, then a 
similar policy is followed of starting at a low level (e.g. 10–20 mg as 
a single dose) and titrating in the light of response.
The choice of immediate—or extended—release preparation

The choice of immediate—or extended—release preparation 
should be discussed with the family. School children often have 
a strong preference for a single tablet to be taken in the morning 
before school, so as to avoid stigmatization. Schools should also be part of the decision making, because of the organizational prob-lems for them of maintaining secure storage and accurate adminis-tration. On the other hand, advantages of immediate-release include lower cost and the possibility of accurate control of the proﬁ le of action through the day.9.2.4 attention deficit and hyperkinetic disorders in childhood and adolescence

SECTION 9  child and adolescent psychiatry 1650
Individual variation in drug response is considerable, so good 
monitoring is a key to achieving good effects. A simple rating scale such as the abbreviated Conners is suitable: a short scale is more likely to be completed than a long one. The wide variety of presen-tations means that key problems for the individual child may not be included on a standard scale. An individualized scale can there-fore be constructed as part of the assessment and used as the prime outcome measure. Ratings by teachers are particularly important, but communication problems can mean that their voice is not heard.

If the dose is set only by the level seen as optimal by the parents, then there is a danger of over-treatment. The child’s behaviour will be seen at home in the mornings and evenings of schooldays, i.e. at times when the blood level of medication is lower than during school hours. The best dose for mornings and evenings may then lead a child being over-controlled and unspontaneous during school hours. Internet feedback from class teacher can be quick and accessible, but care is needed to maintain conﬁ  dentiality. 
T elephone monitoring is useful, especially to allow frequent adjust-ments in the initial phase of setting dosage, but cannot replace individual contact.
Physically, blood pressure and height and weight need regular 
checks; mentally, the examiner should be alert to the possibilities that agitation, depression, loss of spontaneity and perseveration can appear as a result of medication and not only as part of the condition.

Under some circumstances, atomoxetine is the medication of 
ﬁ rst choice. It is not a controlled drug, and does not maintain an 
illicit market, so it may be preferred if there is a substance-misusing

illicit market, so it may be preferred if there is a substance-misusing 
family member. The media controversy over the use of stimulants has entailed that atomoxetine may be acceptable to some families who reject ‘Ritalin’ . It may also be preferred in the presence of T ourette disorder and perhaps of high levels of anxiety. Children who have failed to respond to a stimulant may nevertheless show a good response to atomoxetine. The balance of adverse effects is somewhat different and atomoxetine may therefore be preferred when, for example, insomnia has resulted from stimulants or is a major problem in itself. The action of atomoxetine may take some weeks to appear, and close titration is not recommended. Rather, a test dose around 0.5 mg/kg is given (in case adverse effects appear even on a small dose), and is followed after a week by an increase to 1.2 mg/kg.
Treatment in comorbid conditions

In general, and as considered in ‘Diagnosis’ above, the cluster of ADHD symptoms is similar whether or not co-existent disorders are present. The principles are for the most part the same as when treating uncomplicated ADHD. In the most frequent combi-nation—of ADHD and conduct disorder—stimulant treatment can reduce antisocial problems as well as the core of ADHD
(57) and 
is often worth trying even before conduct disorder is addressed.
In the combination of ADHD and anxiety states, there is some trial evidence that the superiority of stimulant to placebo is less than in ADHD without anxiety.
(10,69)  There may need to be particular 
attention to monitoring both problems in establishing the correct dose level, and atomoxetine will sometimes be chosen. The reasons for anxiety should be sought and corrected.(b) Pervasive developmental disorders

When an autism spectrum disorder is also present, then treatment of ADHD with stimulants is possible, but particular attention needs to be given to the possibility of exacerbating social with-drawal and repetitive patterns of behaviour, and monitoring these should be given a priority as high as detecting the desired effects. The RUPP Autism Network
(70) treated 72 cases in a design with 
a 1-week test period, 4 weeks randomized crossover, and 8 weeks of continued treatment for those who responded well. Methylphenidate produced a better reduction of hyperactive behaviour than did placebo. The most satisfactory dose level was a modest 0.25 mg/kg.
(c) Substance misuse
In the presence of substance misuse, many clinicians are wary of prescribing the potentially misusable stimulants. There may be too much hesitation. People with ADHD taking stimulants show lower rates of substance misuse than those who do not take prescribed medication.
(71)
(d) Epilepsy

(71)
The presence of epilepsy raises extra needs in assessment before treatment. In poorly controlled epilepsy, ADHD symptoms may be the direct result of very frequent small seizures (‘absence status’ at the extreme) or of very frequent seizures at night, so ambulant and sleeping EEGs are useful. In less extreme cases, brief lapses of attention can be the result of minor seizures causing transient cog-nitive impairment; simultaneous recording of EEG with behaviour observation and/or psychological test performance is the best way of getting the answer. Anticonvulsant medications can also cause disturbances of attention and irritability; the clues come from high blood levels of anticonvulsants, low folate levels, polypharmacy, and a temporal relationship between drug changes and hyperactiv-ity or inattention. Once these are excluded, then treatment of

ADHD can proceed as usual. Methylphenidate, it has been copied from textbook to textbook, can worsen epilepsy. I have not been 
able to ﬁ  nd empirical evidence for this, do not ﬁ  nd that it matches 
with clinical experience and regard methylphenidate as safe in con-trolled epilepsy. Atomoxetine has had numerous reports of seizures following its use, but very few of ﬁ  rst seizures. In uncontrolled 
epilepsy, and especially where there is a risk for status epilepticus, I prefer to use dexamfetamine.
Review after a satisfactory response
When a child has responded well to the ﬁ  rst treatment chosen, 
a specialist’s review of the case is in order.
Is the improvement sufﬁ  cient? Impulsiveness and inattentiveness 
may not have disappeared entirely; but the goal should be that they are no longer impairing. If the problems are still more than minor, then the other main intervention should be explored.
What has happened to any co-existent disorders: are they satis-

factorily resolved or is further treatment or referral indicated?
Has the improvement led to different understanding of the child? 
Old habits of reacting to the children or setting expectations for 
them may need to be modiﬁ  ed. At home, parents may well have 
found that they set disciplinary sanctions at a high level when the need was to have an impact on an inattentive person. Those sanc-tions may be too severe, for a person who is now more responsive to reward and punishment and lead to distress or discouragement.

1651
At school, there may be opportunities for normalizing the 
curriculum. Social skills learning, which may have been abandoned in the past because of the child’s failure to proﬁ  t, may now be well 
worth another try.
Does the child understand the nature of the improvement? This,

Does the child understand the nature of the improvement? This, 
like the nature of the disability, will need discussing in different ways as the child matures. The initial reaction may well be one simply of relief at being out of trouble. If, however, medicines are seen as a tablet ‘to make me good’ , this attitude may lead to a rejec-tion of medicine in adolescence when rejecting other aspects of adult authority. There are usually many decisions to make about medication—whether to take it during the school holidays and at weekends, whether to vary the dose in line with environmental demands, and whether to continue taking it even though indulging in alcohol or cannabis. There is every reason to involve the child as an active agent in these decisions and to help them to learn from the consequences.
For how long should the treatment continue? Scientiﬁ  c study has

For how long should the treatment continue? Scientiﬁ  c study has 
not given a secure answer to this question, and individual decision making is needed. Periodic spells off medication—perhaps for a fortnight every two years—is a good way of deciding whether it is still needed. These are also good times for the patient to review why he is taking it, and perhaps to seek the reactions of others to his state off medication.
Are there satisfactory follow-up arrangements? Shared care 
between primary care and the specialist service is the ideal, with physical monitoring (perhaps 6-weekly) and minor dose adjust-ments carried out in primary care, and psychological monitoring and strategy decisions about therapy (perhaps 6-monthly) carried out by the specialist team.
Review in refractory cases
A case can be considered refractory when the problems are still impairing after the exhibition of methylphenidate (or dexamfet-amine), atomoxetine and behavioural therapy.

There are several reasons for failure at the ﬁ  rst line, of which 
failure to follow treatment is the commonest. If behaviour modiﬁ  -
cation was the ﬁ  rst line tried, and the child was too hyperactive for 
it to be adequately delivered, then it may well be worth another try in combination with medication, even if the medication alone was not obviously successful. If medication was not taken, then the reason may have been stigma and careful discussion may allow a more successful attempt. Public controversy about ADHD and medication has been intense for decades and has not been resolved by increasing knowledge. It is right for there to be strong debate, not least because the issues raised—of whether it is legitimate 
to make changes in one’s learning and social abilities through

to make changes in one’s learning and social abilities through 
physical methods—arise in many other areas of public concern. Unfortunately, however, some journalism accuses parents and teachers of bad faith, in pretending a physical cause to disguise failings in parental childrearing or inadequacies in schools. This is understandably disquieting for children and those around them. Involvement with a user group can help to maintain a positive attitude to overcoming disability, and counter some of the noxious attitudes expressed in some of the media.
Another reason for failure of medication is the appearance 
of adverse effects, either precluding the treatment or limiting the dose to subtherapeutic levels. Symptomatic treatment of adverse reactions is often possible.Appetite loss  can result from stimulants (and less commonly from

atomoxetine). This will often disappear towards the end of the day, as the medication is cleared from the body, so increased intake in the evenings (or at weekends or other holidays from stimulant medication) is often enough to prevent faltering in growth.
Insomnia  is a frequent complaint, but should be carefully recorded 
at baseline as it often precedes medication. The commonest prob-lem to result from stimulants is a delay in settling and falling asleep. Sleep hygiene measures can help, for instance, a planned decelera-tion of activity towards bedtime (perhaps in a place other than the bedroom, to avoid conditioning the bedroom environment to wakefulness); a reduction in light intensity (including sitting farther away from the television or computer screen); and prescrip-tion of melatonin shortly before settling. A switch from stimulants to atomoxetine may be needed.
Tics can be worsened or produced by stimulants. Some people

Tics can be worsened or produced by stimulants. Some people 
ﬁ nd that mild tics are a price worth paying for the beneﬁ  cial actions, 
or not even notice them; but they can be disﬁ  guring and stigmatizing. 
A switch to atomoxetine will often be the ﬁ  rst action; or the 
combination of methylphenidate with clonidine may be useful in both reducing tic severity and reducing the necessary dose of methylphenidate.
Treatment can also fail because the initial assessment was incom-
plete and set the wrong targets for therapy. Another disorder may have masqueraded as ADHD (see ‘Diagnosis’) and a failure to respond should raise the index of suspicion for the presence of autistic or hypomanic overactivity. (The converse, however, does not hold; a response to methylphenidate does not make the diag-nosis of ADHD, because qualitatively similar changes can be seen when ordinary children receive a stimulant, vide Rapoport et al.)
(72)

(72)
A variant of this comes when ADHD was present, but not the main 
problem, and the main problem perceived by parents or teachers is not drug-sensitive.
When the above reasons for failure to respond to treatment have 
been considered and dealt with, then the psychiatrist should consider some of the wide variety of unlicensed medications that have been shown effective in randomized controlled trials.
Some noradrenergic agents (clonidine, guanfacine), may act to 
stimulate presynaptic autoreceptors and may downregulate noradrenergic activation. They can be useful when there is a great deal of agitation as part of the symptom pattern (e.g. in autism). They do not, however, improve the cognitive aspects of  inattentiveness.
Modaﬁ  nil has effects in reducing hyperactivity and may enhance 
cognition as well. A licence has been applied for, but was interrupted 
by the possible emergence of skin disorders as a complication.
Tricyclic antidepressants (e.g. imipramine, protriptyline) and

Tricyclic antidepressants (e.g. imipramine, protriptyline) and 
some other antidepressants (bupropion, but not SSRIs) are more effective than placebo in reducing hyperactivity; their effect often 
wanes after a few weeks or months, but they can be useful for short 
periods, e.g. to allow a period off stimulants in a child with a growth problem.
Monoamine oxidase inhibitors also reduce hyperactivity; they 
are in general unsafe for use in children, partly because of the difﬁ culty in maintaining dietary restrictions, but the reversible 
MAOIs such as meclobomide are somewhat safer and could be 
considered. Nicotine patches can be considered for their combina-tion of cognitive and behavioural effects, but quite often produce nausea and local irritation.9.2.4 attention deficit and hyperkinetic disorders in childhood and adolescence

SECTION 9  child and adolescent psychiatry 1652
Risperidone and other atypical neuroleptics are often used, 
especially in intellectually impaired populations, but have not been evaluated for the treatment of ADHD. Their power, and the reason they are prescribed, is in the symptomatic reduction of severely aggressive and agitated behaviour rather than the improvement of attentive and reﬂ  ective behaviour. Clarity of indication is there-
fore important, and their beneﬁ  ts should be set against the many 
hazards.
Some efficacious drugs have been contraindicated because

hazards.
Some efficacious drugs have been contraindicated because 
of rare but severe, adverse effects: pemoline after reports of liver failure, desipramine because of cardiac toxicity. In general, the use of unlicensed or unevaluated drugs should be embarked on only by prescribers with specialist experience, who obtain carefully informed consent and monitor appropriately. The most effective medication protocol yet evaluated was that of the MTA approach (see above), in which stimulants were sufﬁ  cient for about 90 per 
cent of cases and there was little recourse to the second line of drugs.
Treatment in adult life
A key problem in current knowledge is that of making an accurate diagnosis when adults present for the ﬁ  rst time. Adults may be 
mistaken in identifying themselves (see above); but their recall of their childhoods is a reasonably reliable predictor of their parents’ ratings.

(73) Self-report scales have emerged(74, 75)  but are not yet 
fully validated. The account of somebody who knows the patient well—perhaps a spouse or a partner—is very desirable, but does of course need interpreting in the light of their own interests in a diagnosis.
Psychosocial treatment for adults is not yet well evaluated. 
In principle, adults ought to have greater capacities for cognitive and other self-instructional approaches. Y oung and Bramham
(76)
provide a useful guide. Simply the giving of a diagnosis comes as a relief to some who have puzzled over the reasons for their failures, and can liberate problem-solving approaches.
Treatment with stimulant drugs and atomoxetine has been 
evaluated by several randomized controlled trials in adults (reviewed by Faraone et al . and Banaschewski et al .).
(58,60)  The

(58,60)  The 
drugs are efﬁ  cacious. Only atomoxetine has a licence in Europe, 
and that only when treatment was started in childhood; but it does not seem reasonable to withhold a therapy because it was unavail-able to the person earlier. Their use follows similar principles to those described above for children, and Asherson
(77) provides a guide.
In conclusion, this chapter has presented a picture of ADHD and 
its severe form, hyperkinetic disorder, as disabilities that change with development and are often accompanied by other problems that can mask it or themselves be masked by it. They are rewarding challenges for diagnosis and treatment in adulthood as well as during childhood and adolescence.
The National Institute of Mental Health (NIMH) Website: http://www.

nimh.nih.gov/health/topics/attention-deﬁ  cit-hyperactivity-disorder-
adhd/index.shtml
The National Attention Deﬁ  cit Disorder Information and Support Service 
(ADDISS) Website: www.addiss.co.uk
Eric, T. (ed.) (2007). People with Hyperactivity: Understanding and Managing 
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9.2.5 Conduct disorders in 
The term conduct disorder refers to a persistent pattern of antiso-

cial behaviour in which the individual repeatedly breaks social rules and carries out aggressive acts which upset other people. It is the commonest psychiatric disorder of childhood across the world, and the commonest reason for referral to child and adolescent mental health services in Western countries. Antisocial behaviour has the highest continuity into adulthood of all measured human traits except intelligence. A high proportion of children and adoles-cents with conduct disorder grow up to be antisocial adults with impoverished and destructive lifestyles; a signiﬁ  cant minority will 
develop antisocial personality disorder (psychopathy). The disor-der in adolescence is becoming more frequent in Western countries and places a large personal and economic burden on individuals and society.

Relation to other disorders
Conduct disorder is one of the two disruptive disorders  of childhood, 
(also known as externalizing disorders ); the other is the hyperki-
netic syndrome (ICD 10), a more severe form of attention-deﬁ  cit 
hyperactivity disorder (ADHD, DSM IV-R). Conduct disorder and the hyperkinetic syndrome are distinct disorders but often co-occur. As discussed in Chapter 9.1.1 on classiﬁ  cation, disruptive 
disorders can be distinguished on a number of criteria from the other main grouping of child psychiatric conditions, the emotional 
disorders  (also known as internalizing disorders ). For example, 
unlike emotional disorders, disruptive disorders are commoner in boys, the socially disadvantaged, children from large families, and where there is parental discord.
Juvenile delinquency is a legal term referring to an act by a young 
person who has been convicted of an offence which would be 
deemed a crime if committed by an adult. Most, but not all,

deemed a crime if committed by an adult. Most, but not all, 
recurrent juvenile offenders have conduct disorder. In this chapter the term conduct disorder is used as deﬁ  ned by ICD 10 diagnostic 
criteria; the term conduct problems will be used for less severe antisocial behaviour.
Social problem or medical diagnosis?
Infringement of the rights of other people is a requirement for the diagnosis of conduct disorder. Since the manifestations include a

1655
failure to obey social rules despite apparently intact mental state 
and social capacities, many have seen the disorder as principally socially determined. They therefore believe the responsibility for its cause and elimination lies with people who can inﬂ  uence the 
socialization process, such as parents, schoolteachers, social service departments, and politicians. Due to the impossibility of their seeing all cases, there is some debate within child and adolescent psychiatry as to whether doctors and mental health professionals should be involved in any but the most complex presentations.
(1)
Some have argued that involvement of medical personnel carries the risk of their becoming agents of social control through the misapplication of diagnostic labels, which may lead to abuses of 
the kind seen in some totalitarian regimes.
However, advances in the last decade have shown there are sub-

stantial genetic and biological contributions to conduct disorder, and in some cases the symptoms may be responsive to medication. Work in the last 25 years mainly from the ﬁ  eld of child and adoles-
cent mental health has clariﬁ  ed many of the mechanisms contrib-
uting to the development and persistence of antisocial behaviour, and has led to the development of effective treatments. As yet these are not being widely used with the children and adolescents who need them. Therefore psychiatrists need to be able to contribute to 
the planning and delivery of an appropriate service.
Aggressive and deﬁ  ant behaviour is an important part of normal 
child and adolescent development which ensures physical and social survival. Indeed, parents may express concern if a child is too acquiescent and unassertive. The level of aggressive and deﬁ  ant

child and adolescent development which ensures physical and social survival. Indeed, parents may express concern if a child is too acquiescent and unassertive. The level of aggressive and deﬁ  ant 
behaviour varies considerably amongst children, and it is probably most usefully seen as a continuously distributed trait. Empirical studies do not suggest a level at which symptoms become qualita-tively different, nor is there a single cut-off point at which they become impairing for the child or a clear problem for others. There is no hump towards the end of the distribution curve of severity to suggest a categorically distinct group who might on these grounds warrant a diagnosis of conduct disorder.
Picking a particular level of antisocial behaviour to call conduct

Picking a particular level of antisocial behaviour to call conduct 
disorder is therefore necessarily arbitrary. For all children, the expression of any particular behaviour also varies according to child age, so that for example physical hitting is at a maximum at around 2 years of age but declines to a low level over the next few years. Therefore any judgement about the signiﬁ  cance of the level 
of antisocial behaviour has to be made in the context of the child’s age. Before deciding that the behaviour is abnormal or a signiﬁ  cant 
problem, a number of other clinical features have to be considered:
◆ Level: severity and frequency of antisocial acts, compared with children of the same age and gender
◆ Pattern: the variety of antisocial acts, and the setting in which they are carried out
◆ Persistence: duration over time
◆ Impact: distress and social impairment of child; disruption and damage caused to others.
Change in clinical features with age

The type of behaviour seen will depend on the age and gender of the individual.Younger children , say from 3 to 7 years of age, usually present 
with general deﬁ  ance of adults wishes, disobedience of instruc-
tions, angry outbursts with temper tantrums, physical aggression to people especially siblings and peers, destruction of property, 
arguing, blaming others for things that have gone wrong, and a tendency to annoy and provoke others.
In middle childhood , say from 8 to 11, the above features are often 
present but as the child grows older, stronger, and spends more time out of the home, other behaviours are seen. They include: swearing, lying about what they have been doing, stealing of others belongings outside the home, persistent breaking of rules, physical ﬁ  ghts, bully-

ing of other children, cruelty to animals, and setting of ﬁ  res.
In adolescence , say from 12 to 17, more antisocial behaviours are 
often added: cruelty and hurting of other people, assault, robbery 
using force, vandalism, breaking and entering houses, stealing from 
cars, driving and taking away cars without permission, running away from home, truanting from school, extensive use of narcotic drugs.
Not all children who start with the type of behaviours listed in 
early childhood progress on to the later, more severe forms. Only about half continue from those in early childhood to those in middle childhood
(2); likewise only about a further half of those with the

(2); likewise only about a further half of those with the 
behaviours in middle childhood progress to show the behaviours listed for adolescence. However, the early onset group are impor-tant as they are far more likely to display the most severe symptoms in adolescence, and to persist in their antisocial tendencies into adulthood. Indeed over 90 per cent of severe, recurrent adolescent offenders showed marked antisocial behaviour in early childhood. In contrast, there is a large group who only start to be antisocial in adolescence, but whose behaviours are less extreme and who tend to desist by the time they are adults.
Girls

Girls
Severe antisocial behaviour is less common in girls who are less likely to be physically aggressive and engage in criminal behaviour, but more likely to show spitefulness, emotional bullying (such as excluding children from groups, spreading rumours so others are rejected by their peers), frequent unprotected sex leading to sexually transmitted diseases and pregnancy, drug abuse, and running away from home.
Pattern and setting

Prognosis is determined by the frequency and intensity of antisocial behaviours, the variety of types, the number of settings in which they occur (e.g. home, school, and in public), and their persistence. For general populations of children, the correlation between parent and teacher ratings on the same measures is only 0.2 to 0.3, so that there are many children who are perceived to be mildly or moder-ately antisocial at home but well behaved at school, and vice versa. However, for more severe antisocial behaviour, there are usually manifestations both at home and at school.
Impact

Impact
At home the child often is subject to high levels of criticism and hostility, and sometimes made a scapegoat for a catalogue of family misfortunes. Frequent punishments and physical abuse are not uncommon. The whole family atmosphere is often soured and siblings also affected. Maternal depression is often present, and families who are unable to cope may, as a last resort, give up the child to be cared for by the local authority. At school, teachers may 9.2.5 conduct disorders in childhood and adolescence

SECTION 9  child and adolescent psychiatry 1656
take a range of measures to attempt to control the child and protect 
the other pupils, including sending the child out of the class, some-times culminating in permanent exclusion from the school. This may lead to reduced opportunity to learn subjects on the curriculum and poor examination results. The child typically has few if any friends, who get fed up with their aggressive behaviour. This often leads to exclusion from many group activities, games, and trips, so restricting the child’s quality of life and experiences. On leaving school the lack of social skills, low level of qualiﬁ  cations, and pres-
ence of a police record make it harder to gain employment.
The ICD-10 classiﬁ  cation has a category for conduct disorders, 
F91. The Clinical descriptions and diagnostic guidelines(3) state:
Examples of the behaviours on which the diagnosis is based include

Examples of the behaviours on which the diagnosis is based include 
the following: excessive levels of ﬁ  ghting or bullying; cruelty to ani-
mals or other people; severe destructiveness to property; ﬁ  resetting; 
stealing; repeated lying; truancy from school and running away from home; unusually frequent and severe temper tantrums; defiant provocative behaviour; and persistent severe disobedience. Any one of these categories, if marked, is sufﬁ  cient for the diagnosis, but isolated 
dissocial acts are not. (p. 267)
An enduring pattern of behaviour should be present, but no time 
frame is given and there is no impairment or impact criterion stated.
The ICD-10 Diagnostic criteria for research
(4) differ, requiring

(4) differ, requiring 
symptoms to have been present for at least 6 months, and the introductory rubric indicates that impact upon others (in terms of violation of their basic rights), but not impairment of the child, can contribute to the diagnosis. The research criteria take a menu-driven approach whereby a certain number of symptoms have to be present. 15 behaviours are listed to consider for the diagnosis of Conduct Disorder , which usually but not exclusively apply to 
older children and teenagers. They can be grouped into four classes:
(a) Aggression to people and animals
◆ often lies or breaks promises to obtain goods or favours or to avoid obligations
◆ frequently initiates physical ﬁ  ghts (this does not include ﬁ  ghts 
with siblings)
◆ has used a weapon that can cause serious physical harm to others (e.g. bat, brick, broken bottle, knife, gun)

◆ often stays out after dark despite parenting prohibition (begin-ning before 13 years of age)
◆ exhibits physical cruelty to other people (e.g. ties up, cuts, or burns a victim), and
◆ exhibits physical cruelty to animals.
(b) Destruction of property
◆ deliberately destroys the property of others (other than by ﬁ  re-
setting) and
◆ deliberately sets ﬁ  res with a risk or intention of causing serious 
damage).(c) Deceitfulness or theft
◆ steals objects of non-trivial value without confronting the vic-tim, either within the home or outside (e.g. shoplifting, burglary, forgery).
(d) Serious violations of rules
◆ is frequently truant from school, beginning before 13 years of age

◆ has run away from parental or parental surrogate home at least twice or has run away once for more than a single night (this does not include leaving to avoid physical or sexual abuse)
◆ commits a crime involving confrontation with the victim (including purse-snatching, extortion, mugging)
◆ forces another person into sexual activity
◆ frequently bullies others (e.g. deliberate inﬂ  iction of pain or hurt, 
including persistent intimidation, tormenting, or molestation), and
◆ breaks into someone else’s house, building, or car.
T o make a diagnosis, three symptoms from this list have to be 
present, one for at least 6 months. There is no impairment criterion. There are three subtypes: conduct disorder conﬁ  ned to the family 
context  (F91.0), unsocialized conduct disorder  (F91.1, where the 
young person has no friends and is rejected by peers), and social-

ized conduct disorder  (F91.2, where peer relationships are normal). 
It is recommended that age of onset be speciﬁ  ed, with childhood 
onset type  manifesting before age 10, and adolescent onset type  after. 
Severity should be categorized as mild ,moderate , or severe  accord-
ing to number of symptoms or impact on others, e.g. causing severe 
physical injury, vandalism, theft.
For younger children, say up to 9 or 10 years old, there is a list of 
eight symptoms for the subtype known as Oppositional Deﬁ  ant 
Disorder  (F91.3):
1 has unusually frequent or severe temper tantrums for his or her 
developmental level
2 often argues with adults3 often actively refuses adults’ requests or deﬁ  es rules
4 often, apparently deliberately, does things that annoy other 
people
5 often blames others for his or her own mistakes or misbehaviour

people
6 is often touchy or easily annoyed by others7 is often angry or resentful8 is often spiteful or resentful.
T o make a diagnosis of the oppositional deﬁ  ant type of conduct 
disorder, four symptoms from either  this list or the main conduct 
disorder 15 symptom list have to be present, but no more than two from the latter. Unlike the main variant, there is an impairment criterion: the symptoms must be amaladaptive and inconsistent with the developmental level (p. 161).
Where there are sufﬁ  cient symptoms of a comorbid disorder to 
meet diagnostic criteria, the ICD-10 system discourages the appli-cation of a second diagnosis, and instead offers a single, combined category. There are two major kinds: mixed disorders of conduct

1657
and emotions, of which Depressive Conduct Disorder  (F92.0) is 
the best researched; and Hyperkinetic Conduct Disorder  (F90.1). 
There is modest evidence to suggest these combined conditions may differ somewhat from their constituent elements.
The DSM IV-R system
(5) follows the ICD-10 research criteria 
very closely and does not have separate clinical guidelines. The same 15 behaviours are given for the diagnosis of conduct disorder 312.8, with almost identical wording. As for ICD-10, three symp-toms need to be present for diagnosis. Severity and childhood or adolescent onset are speciﬁ  ed in the same way. However, unlike 
ICD-10, there is no division into socialized/unsocialized, or family context only types, and there is a requirement for the behaviour to 
cause a clinically signiﬁ  cant impairment in social, academic, or

cause a clinically signiﬁ  cant impairment in social, academic, or 
social functioning. Comorbidity in DSM IV-R is handled by giving as many separate diagnoses as necessary, rather than by having single, combined categories.
In DSM IV-R, oppositional deﬁ  ant disorder is classiﬁ  ed as a sep-
arate disorder on its own, and not as a subtype of conduct disorder. Diagnosis requires four symptoms from a list of eight behaviours 
which are the same as for ICD-10, but unlike ICD-10, all four have 
to be from the oppositional list, and none may come from the main conduct disorder list. It is doubtful whether oppositional deﬁ  ant 
disorder differs substantially from conduct disorder in older chil-dren in any associated characteristics, and the value of designating it as a separate disorder is arguable. In this article, the term conduct disorder will henceforth be used as it is in ICD-10, to refer to all variant including oppositional deﬁ  ant disorder.

Making a diagnosis of conduct disorder is usually straightforward 
but comorbid conditions are often missed. The differential diagno-sis may include:
1Hyperkinetic syndrome/Attention-deﬁ  cit hyperactivity disorder .
These are the names given by ICD-10 and DSM IV-R respectively for similar conditions, except that the former is more severe. For convenience the term hyperactivity  will be used here. It is charac-
terized by impulsivity, inattention, and motor overactivity. Any of these three sets of symptoms can be misconstrued as antisocial, particularly impulsivity which is also present in conduct disorder. However, none of the symptoms of conduct disorder are a part of hyperactivity so excluding conduct disorder should not be difﬁ  cult. A frequently made error however, is to miss 
comorbid hyperactivity when conduct disorder is deﬁ  nitely

comorbid hyperactivity when conduct disorder is deﬁ  nitely 
present. Standardized questionnaires are very helpful here, such as the Strengths and Difﬁ  culties Questionnaire, which is brief, 
and just as effective at detecting hyperactivity as much longer alternatives.
(6)
2Adjustment reaction to an external stressor . This can be diagnosed 
when onset occurs soon after exposure to an identiﬁ  able psycho-
social stressor such as divorce, bereavement, trauma, abuse, or adoption. The onset should be within 1 month for ICD-10, and 3 months for DSM IV-R, and symptoms should not persist for more than 6 months after the cessation of the stress or its sequelae.
3Mood disorders . Depression can present with irritability and 
oppositional symptoms but unlike typical conduct disorder mood is usually clearly low and there are vegetative features; also

oppositional symptoms but unlike typical conduct disorder mood is usually clearly low and there are vegetative features; also 
more severe conduct problems are absent. Early manic depressive disorder can be harder to distinguish, as there is often consider-able deﬁ  ance and irritability combined with disregard for rules, 
and behaviour which violates the rights of others. Low self-esteem is the norm in conduct disorder, as is a lack of friends or constructive pastimes. Therefore it is easy to overlook more pro-nounced depressive symptoms. Systematic surveys reveal that around a third of children with conduct disorder have depressive or other emotional symptoms severe enough to warrant a diagnosis.
4Autistic spectrum disorders . These are often accompanied by

4Autistic spectrum disorders . These are often accompanied by 
marked tantrums or destructiveness, which may be the reason for seeking a referral. Enquiring about other symptoms of autis-tic spectrum disorders should reveal their presence.
5Dissocial/antisocial personality disorder . In ICD-10 it is suggested a 
person should be 17 or older before dissocial personality is con-sidered. Since at age 18 most diagnoses speciﬁ  c to childhood and 
adolescence no longer apply, in practice there is seldom difﬁ  culty. 
In DSM IV-R conduct disorder can be diagnosed over 18 so there is potential overlap. A difference in emphasis is the severity and pervasiveness of the symptoms of those with personality disorder, whereby all the individual’s relationships are affected by the behaviour pattern, and the individual’s beliefs about his antisocial behaviour are characterized by callousness and lack of remorse.
6Subcultural deviance . Some youths are antisocial and commit

6Subcultural deviance . Some youths are antisocial and commit 
crimes but are not particularly aggressive or deﬁ  ant. They are 
well adjusted within a deviant peer culture that approves of rec-reational drug use, shoplifting, etc. In some localities a third or more teenage males ﬁ  t this description and would meet ICD-10 
diagnostic guidelines for socialized conduct disorder. Some clini-cians are unhappy to label such a large proportion of the popula-tion with a psychiatric disorder. Using DSM IV-R criteria would preclude the diagnosis for most youths like this due to the requirement for signiﬁ  cant impairment.
Multiaxial assessment
ICD-10 recommends that multiaxial assessment be carried out for

ICD-10 recommends that multiaxial assessment be carried out for 
children and adolescents, while DSM IV-R suggests it for all ages. In both systems axis one is used for psychiatric disorders which have been discussed above. The last three axes in both systems cover general medical conditions, psychosocial problems, and level of social functioning respectively; these topics will be alluded to below under aetiology. In the middle are two axes in ICD-10, which cover speciﬁ  c (Axis two) and general (Axis three) learning disabilities 
respectively; and one in DSM IV-R (Axis two) which covers personality disorders and general learning disabilities.
Both speciﬁ  c and general learning disabilities are essential to 
assess in individuals with conduct problems. Fully a third of chil-dren with conduct disorder also have speciﬁ  c reading retardation
(7)
deﬁ ned as having a reading level two standard deviations below

(7)
deﬁ ned as having a reading level two standard deviations below 
that predicted by the person’s IQ. While this may in part be due to lack of adequate schooling, there is good evidence that the cogni-tive deﬁ  cits often precede the behavioural problems. General learn-
ing disability (mental retardation) is often missed in children with 
conduct disorder unless IQ testing is carried out. The rate of con-
duct disorder rise several-fold as IQ gets below 70.9.2.5 conduct disorders in childhood and adolescence

SECTION 9  child and adolescent psychiatry 1658
Between 5 per cent and 10 per cent of children and adolescents 
have signiﬁ  cant persistent oppositional, disruptive, or aggressive 
behaviour problems.(8, 9) With respect to historical period, a mod-
est rise in diagnosable conduct disorder over the second half of the twentieth century has also been observed comparing assessments of three successive birth cohorts in Britain.
(10) There is a marked 
social class gradient.(9) With respect to ethnicity, youth self-reports 
of antisocial behaviours, and crime victim survey reports of perpe-trators’ ethnicity show an excess of offenders of black African ancestry. Importantly, Hispanic Americans in the United States of America and British Asians in the United Kingdom do not tend to show an excess of offending compared to their white counterparts.
Sex differences in prevalence

The sex ratio is approximately 2:5 males for each female overall, with males further exceeding females in the frequency and severity of behaviours. On balance, research suggests that the causes of conduct problems are the same for the sexes, but males have more conduct disorder because they experience more of its individual-level risk factors (e.g. hyperactivity, neurodevelopmental delays). However, recent years have seen increasing concern amongst clinicians about treating antisocial behaviour amongst girls.
(11)
Developmental subtypes
Life-course persistent versus adolescence-limited
There has been considerable attention paid to the distinction between conduct problems that are ﬁ  rst seen in early childhood ver-
sus those that start in adolescence
(2) and these two subtypes are

(2) and these two subtypes are 
encoded in the DSM-IV . Early onset is a strong predictor of persis-tence through childhood, and early onset delinquency is more likely to persist into adult life. Those with early onset differ from those with later onset in that they have lower IQ, more attentional and impulsivity problems, poorer scores on neuropsychological tests, greater peer difﬁ  culties and they are more likely to come from 
adverse family circumstances.
(2) Those with later onset become 
delinquent predominantly as a result of social inﬂ  uences such as 
association with other delinquent youths. Findings from the follow-up of the Dunedin cohort support relatively poorer adult outcomes for the early onset group in domains of violence, mental health, substance abuse, work, and family life.

(2) However the ‘adolescence-
limited’ group were not without adult difﬁ  culties. As adults they still 
engaged in self-reported offending, and they also had problems with alcohol and drugs. Thus, the age-of-onset subtype distinction has strong predictive validity, but adolescent onset antisocial behaviours may have more long-lasting consequences than previously sup-posed, and so both conduct problems warrant clinical attention.
Aetiology
Individual-level characteristics
(a) Identiﬁ  ed genotypes
The search for specific genetic polymorphisms is a very new 
scientiﬁ  c initiative, and little has yet been accomplished. The most-
studied candidate gene in relation to conduct problems is the MAOA promoter polymorphism. The gene encodes the MAOA enzyme, which metabolizes neurotransmitters linked to aggressive behaviour. Replicated studies show that maltreatment history and 
genotype interact to predict antisocial outcome.
(12)
(b) Perinatal complications and temperament

(12)
Recent large-scale general population studies have found associa-tions between life-course persistent type conduct problems and perinatal complications, minor physical anomalies, and low birth weight.
(13) Most studies support a biosocial model in which obstetric 
complications might confer vulnerability to other co-ocurring risks such as hostile or inconsistent parenting. Smoking in pregnancy is a statistical risk predictor of offspring conduct problems,
(13) but a 
causal link between smoking and conduct problems has not been established. Several prospective studies have shown associations between irritable temperament and conduct problems.
(14)
(c) Neurotransmitters
In general the ﬁ  ndings with children have not been consistent.(15)
For example, in the Pittsburgh Y outh cohort, boys with long-stand ing

(14)
For example, in the Pittsburgh Y outh cohort, boys with long-stand ing 
conduct problems showed downward changes in urinary adrena-line level following a stressful challenge task, whereas prosocial boys showed upward responses. However other studies have failed to ﬁ nd an association between conduct disorder and measures 
of noradrenaline in children.
(15) It should be borne in mind that 
neurotransmitters in the brain are only indirectly measured, most measures of neurotransmitter levels are crude indicators of activity, and little is known about neurotransmitters in the juvenile brain.
(d) Verbal deﬁ  cits and autonomic reactivity
Children with conduct problems have been shown consistently to 
have increased rates of deﬁ  cits in language-based verbal skills.(16)
The association holds after controlling for potential confounds

The association holds after controlling for potential confounds 
such as race, socio-economic status, academic attainment, and test motivation. Children who cannot reason or assert themselves verbally may attempt to gain control of social exchanges using aggression; there are likely also to be indirect effects in which low verbal IQ contributes to academic difﬁ  culties which in turn mean 
that the child’s experience of school becomes unrewarding, rather than a source of self-esteem and support.
A low resting pulse rate or slow heart rate has been found consis-
tently to be associated with antisocial behaviour, and a meta-analysis
of 40 studies suggested it is the best replicated biological correlate 
of antisocial behaviour.
(17) Other psychophysiological indicators 
show that antisocial and psychopathic boys are also slowest to

show that antisocial and psychopathic boys are also slowest to 
show a skin-conductance response to aversive stimuli.(17) The 
explanation for the link between slow autonomic activity and antisocial behaviour remains unclear.
(e) Information-processing and social cognition
Dodge proposed the leading information-processing model for the genesis of aggressive behaviours within social interactions.
(18) The 
model hypothesises that children who are prone to aggression focus on threatening aspects of others’ actions, interpret hostile intent in the neutral actions of others, and are more likely to select and to favour aggressive solution to social challenges. Several studies have demonstrated that aggressive children make such errors of social cognition.
(18)
Risks outside the family
(a) Risks in the neighbourhood

(18)
It has long been assumed that bad neighbourhoods have the effect of encouraging children to develop conduct problems. Many parents

1659
strive to secure the best neighbourhood and school for their child 
that they can afford. Although it is obvious that some local areas have higher crime rates than others, it has been difﬁ  cult to docu-
ment any direct link between neighbourhood characteristics and child behaviour, for a number of reasons. For example, neighbour-hood characteristics were conceptualized in overly simple struc-tural-demographic terms such as percentage of non-white residents or percentage of single-parent households. Moreover, research designs could not rule out the alternative possibility that families whose members are antisocial tend to selectively move into bad neighbourhoods. A new generation of neighbourhood research is addressing these challenges, and suggests that the neighbourhood factors that are important include social processes such as ‘collec-tive efﬁ  cacy’ and ‘social control’ , do inﬂ  uence young children’s con-

duct problems, probably by supporting parents in their efforts to rear children.
(b) Peer inﬂ  uences
Children with conduct problems have poorer peer relationships 
than non-disordered children in that they tend to associate with children with similar antisocial behaviours, they have discordant interactions with other children, and experience rejection by non-deviant peers. Three processes have been identiﬁ  ed, namely that 
children’s antisocial behaviours lead them to have peer problems, deviant peer relationships lead to antisocial behaviours, and thirdly some common factor leads to both.
(19)
Risks within the family
(a) Concentration of crime in families
Fewer than 10 per cent of the families in any community account for more than 50 per cent of that community’s criminal offenses, which reﬂ  ects the coincidence of genetic and environmental risks.

Fewer than 10 per cent of the families in any community account for more than 50 per cent of that community’s criminal offenses, which reﬂ  ects the coincidence of genetic and environmental risks. 
There is now solid evidence from twin and adoption studies that conduct problems assessed both dimensionally and categorically are substantially heritable.
(20) However, knowing that conduct 
problems are under some genetic inﬂ  uence is less useful clinically 
than knowing that this genetic inﬂ  uence appears to be reduced, or

than knowing that this genetic inﬂ  uence appears to be reduced, or 
enhanced, depending on interaction with circumstances in the child’s environment. Several genetically sensitive studies have allowed interactions between family genetic liability and rearing environment to be examined. Both adoption and twin studies have reported an interaction between antisocial behaviour in the biological parent and adverse conditions in the adoptive home that predicted the adopted child’s antisocial outcome, so that the genetic risk was modiﬁ  ed by the rearing environment.
(b) Family poverty
There is an association between severe poverty and early childhood

There is an association between severe poverty and early childhood 
conduct problems. Early theories proposed direct effects of poverty related to strains arising from the gap between aspirations and realities, and from lacking opportunity to acquire social status and prestige. Subsequent research has indicated that the association between low income and childhood conduct problems is indirect, mediated via family processes such as marital discord and parent-ing deﬁ  cits.
(c) Parent–child attachment
Parent–child relationships provide the setting for the development 
of later social functioning, and disruption of these attachment rela-tionships, for example through institutional care, is associated with subsequent difﬁ  culties in relating. Thus, conduct problems might 
be expected to arise from infant attachment difﬁ  culties. One study

be expected to arise from infant attachment difﬁ  culties. One study 
found that ambivalent and controlling attachment predicted exter-nalizing behaviours after controlling for baseline externalizing problems
(21); disorganized child attachment patterns seem to be 
especially associated with conduct problems. Although it seems obvious that poor parent–child relations in general predict conduct problems, it has yet to be established whether attachment difﬁ  cul-
ties as measured by observational paradigms have an independent causal role in the development of behaviour problems; attachment classiﬁ  cations could be markers for other relevant family risks.
(d) Discipline and parenting
Patterns of parenting associated with conduct problems were delin-
eated by Patterson in his seminal work Coercive Family Process .(22)
Parents of antisocial children were found to be more inconsistent

Parents of antisocial children were found to be more inconsistent 
in their use of rules, to issue more, and unclear, commands, to be more likely to respond to their children on the basis of mood rather than the characteristics of the child’s behaviour, to be less likely to monitor their children’s whereabouts, and to be unresponsive to their children’s prosocial behaviour. Patterson proposed a speciﬁ  c 
mechanism for the promotion of oppositional and aggressive behaviours in children. A parent responds to mild oppositional behaviour by a child with a prohibition to which the child responds by escalating his behaviour, and mutual escalation continues until the parent backs off thus negatively reinforcing the child’s behav-iour. The parent’s inconsistent behaviour increases the likelihood of the child showing further oppositional or aggressive behaviour.

In addition to speciﬁ  c tests of Patterson’s reinforcement model 
there is ample evidence that conduct problems are associated with hostile, critical, punitive, and coercive parenting.
(23)
In considering the role of coercive processes in the origins or 
maintenance of conduct problems, we need to consider possible alternative explanations, (i) that the associations reﬂ  ect familial 
genetic liability towards children’s psychopathology and parents’ coercive discipline, (ii) that they represent effects of children’s behaviours on parents, and (iii) that coercive parenting may be a correlate of other features of the parent/child relationship or family functioning that inﬂ  uence child behaviours. There is considerable 
evidence that children’s difﬁ  cult behaviours do indeed evoke paren-

tal negativity. The fact that children’s behaviours can evoke nega-tive parenting does not however mean that negative parenting has no impact on children’s behaviour. The E-risk longitudinal twin study of British families examined the effects of fathers’ parenting on young children’s aggression.
(24) As expected, a prosocial father’s 
absence  predicted more aggression by his children. But in contrast, 
an antisocial father’s presence  predicted more aggression by his 
children, and his harmful effect was exacerbated the more time each week he spent taking care of the children.
(e) Exposure to adult marital conﬂ  ict and domestic violence
It is likely that family processes other than parenting skills and

It is likely that family processes other than parenting skills and 
quality of parent–child attachment relationships have a role. Many studies have shown that children exposed to domestic violence between adults are subsequently more likely to themselves become aggressive. Cummings and Davies
(25) proposed that marital con-
ﬂ ict inﬂ  uences children’s behaviour because of its effect on their 
regulation of emotion. For example a child may respond to fright-ening emotion arising from marital conﬂ  ict by down-regulating 
his own emotion through denial of the situation. This in turn may 9.2.5 conduct disorders in childhood and adolescence

SECTION 9  child and adolescent psychiatry 1660
lead to inaccurate appraisal of other social situations and ineffec-
tive problem-solving. Repeated exposure to family conflict is thought to lower childrens’ thresholds for psychological dysregula-tion, resulting in greater behavioural reactivity to stress.
(25)
Children’s aggression may also be increased by marital discord because children are likely to imitate aggressive behaviour mod-elled by their parents. Through parental aggression children may learn that aggression is a normative part of family relationships, that it is an effective way of controlling others, and that aggression is sanctioned, not punished.
(f) Maltreatment
Physical punishment is widely used, and parents of children with conduct problems frequently resort to it out of desperation. Overall, associations between physical abuse and conduct problems are well established.
(15) In the Christchurch longitudinal study, child sexual

(15) In the Christchurch longitudinal study, child sexual 
abuse predicted conduct problems, after controlling for other childhood adversities.
(26) Links with conduct problems are not 
however straightforward. The risk for conduct problems does not apply equally to all forms of physical punishment. The E-risk lon-gitudinal twin study was able to compare the effects of corporal punishment (smacking, spanking) versus injurious physical mal-treatment using twin-specific reports of both experiences.
(27)

(27)
Results showed that children’s genetic endowment accounted for virtually all of the association between their corporal punishment and their conduct problems. This indicated a ‘child effect’ , in which children’s bad conduct provokes their parents to use more corporal punishment, rather than the reverse. Findings about injurious physical maltreatment were the opposite. There was no child effect provoking maltreatment and moreover, significant effects of maltreatment on child aggression remained after controlling for any genetic transmission of liability to aggression from antisocial parents.
From risk predictor to causation

Associations have been documented between conduct problems and a wide range of risk factors. A variable is called a ‘risk factor’ if it has a documented predictive relation with antisocial outcomes, whether or not the association is causal. The causal status of most of these risk factors is unknown; we know what statistically predicts conduct-problem outcomes, but not how or why. Establishing a causal role for a risk factor is by no means straightforward, particu-larly as it is unethical to experimentally expose healthy children to risk factors to observe whether those factors can generate new con-duct problems. There is no one solution to the problem, although the use of genetically sensitive designs and the study of within-
individual change in natural experiments and treatment studies 
have considerable methodological advantages for suggesting causal inﬂ uences on conduct problems.

Of those with early onset conduct disorder (before eight) about 
half persist with serious problems into adulthood. Of those with adolescent onset, the great majority (over 85 per cent) desist in their antisocial behaviour by their early twenties.
Many of the factors which predict poor outcome are associated 
with early onset (Table 9.2.5.1).
T o detect protective factors, children who do well despite adverse 
risk factors have been studied.These so-called ‘resilient’ children, however, have been shown to

risk factors have been studied.These so-called ‘resilient’ children, however, have been shown to 
have lower levels of risk factors, for example a boy with antisocial behaviour and low IQ living in a rough neighbourhood but living with supportive, concerned parents. Protective factors are mostly the opposite end of the spectrum of the same risk factor, thus good parenting, high IQ are protective. Nonetheless there are factors which are associated with resilience independent of known adverse inﬂ uences. These include a good relationship with at least one 
adult, who does not necessarily have to be the parent; a sense of pride and self-esteem; and skills or competencies.
Adult outcome
Studies of groups of children with early onset conduct disorder indicate a wide range of problems not only conﬁ  ned to antisocial 
acts, as shown in Table 9.2.5.2.
What is clear is that not only are there substantially increased

What is clear is that not only are there substantially increased 
rates of antisocial acts, but that the general psychosocial function-ing of children with conduct disorder grown up is strikingly poor. For most of the characteristics shown in Table 9.2.5.2, the increase Table 9.2.5 .1 Factors predicting poor outcome
Onset Early onset of severe problems, before 8 years of age
Phenomenology Antisocial acts which are severe, frequent, and varied
Comorbidity Hyperactivity and attention problemsIntelligence Lower IQFamily history Parental criminality; parental alcoholismParenting Harsh, inconsistent parenting, with high criticism, low 
warmth, low involvement, and low supervision
Wider environment Low-income family in poor neighbourhood with 
ineffective schools
Table 9.2.5.2  Adult outcome
Antisocial 
behaviourMore violent and non-violent crimes, e.g. mugging, 
grievous bodily harm, theft, car crimes, fraud

Psychiatric problemsIncreased rates of antisocial personality, alcohol and 
drug abuse, anxiety, depression and somatic complaints, 
episodes of deliberate self-harm and completed suicide, 
time in psychiatric hospitals
Education and 
trainingPoorer examination results, more truancy and early school 
leaving, fewer vocational qualiﬁ  cations
Work More unemployment, jobs held for shorter time, jobs 
low status and income, increased claiming of beneﬁ  ts 
and welfare
Social network Few if any signiﬁ  cant friends, low involvement with 
relatives, neighbours, clubs, and organizations
Intimate 
relationshipsIncreased rate of short-lived, violent cohabiting 
relationships; partners often also antisocial
Children Increased rates of child abuse, conduct problems in 
offspring, children taken into care

Health More medical problems, earlier death

1661 9.2.5 conduct disorders in childhood and adolescence
compared to controls is at least double for community cases 
who were never referred, and three to four times for referred children.
(18)
Pathways
The path from childhood conduct disorder to poor adult outcome is neither inevitable nor linear. Different sets of inﬂ  uences impinge 
as the individual grows up and shape the life-course. Many of these can accentuate problems. Thus a toddler with an irritable tempera-ment and short attention span may not learn good social skills if he is raised in a family lacking them, and where he can only get his way by behaving antisocially and grasping for what he needs. At school he may fall in with a deviant crowd of peers, where violence and other antisocial acts are talked up and give him a sense of esteem. His generally poor academic ability and difﬁ  cult behav-

iour in class may lead him to truant increasingly, which in turn makes him fall further behind. He may then leave school with no qualiﬁ  cations and fail to ﬁ  nd a job, and resort to drugs. T o fund his 
drug habit he may resort to crime, and once convicted, ﬁ  nd it even 
harder to get a job. From this example, it can be seen that adverse 
experiences do not only arise passively and independently of the young person’s behaviour; rather, the behaviour predisposes them to end up in risky and damaging environments. Consequently, the number of adverse life events experienced is greatly increased.
(28)
The path from early hyperactivity into later conduct disorder is also not inevitable. In the presence of a warm supportive family atmosphere it is far less likely than if the parents are highly critical and hostile.
Other inﬂ  uences can however steer the individual away from 
and antisocial path. For example, the fascinating follow-up of delinquent boys to age 70 by Laub and Sampson

(29) showed that 
the following led to desistence: being separated from a deviant peer group; marrying to a non-deviant partner; moving away from a poor neighbourhood; military service which imparted skills.
Treatment
Evidence-based treatments
Proven treatments include those which singly or in combination address (i) Parenting skills, (ii) Family functioning, (iii) Child interpersonal skills, (iv) Difﬁ  culties at school, (v) Peer group inﬂ  u-
ences, and (vi) Medication for coexistent hyperactivity.
(a) Parenting skills
Parent management training  aims to improve parenting skills. There 
are scores of randomized controlled trials showing that it is effective for children up to about 10 years old.
(30) They address the 
parenting practices identiﬁ  ed in research as contributing to con-

duct problems. A more detailed account is given by Scott.(30)
Typically, they include ﬁ  ve elements:
(i) Promoting play and a positive relationship
In order to cut into the cycle of deﬁ  ant behaviour and recrimina-
tions, it is important to instil some positive experiences for both sides and begin to mend the relationship. T eaching parents the techniques of how to play in a constructive and non-hostile way with their children helps them recognize their needs and respond sensitively. The children in turn begin to like and respect their parents more, and become more secure in the relationship.(ii) Praise and rewards for sociable behaviour
Parents are helped to reformulate difﬁ  cult behaviour in terms of

Parents are helped to reformulate difﬁ  cult behaviour in terms of 
the positive behaviour they wish to see, so that they encourage wanted behaviour rather than criticize unwanted behaviour. For example, instead of shouting at the child not to run, they would praise him whenever he walks quietly; then he will do it more often. Through hundreds of such prosaic daily interactions, child behav-iour can be substantially modiﬁ  ed. Y et some parents ﬁ  nd it hard 
to praise, and fail to recognize positive behaviour when it happens, with the result that it become less frequent.
(iii) Clear rules and clear commands
Rules need to be explicit and constant; commands need to be ﬁ  rm 
and brief. Thus shouting at a child to stop being naughty doesn’t tell him what he should  do, whereas for example telling him to play 
quietly gives a clear instruction which makes compliance easier.
(iv) Consistent and calm consequences for unwanted behaviour

Disobedience and aggression need to be responded to ﬁ  rmly and 
calmly, but for example putting the child in a room for a few min-utes. This method of timeout from positive reinforcement sounds simple but requires considerable skill to administer effectively. More minor annoying behaviours such as whining and shouting often respond to being ignored, but again parents often ﬁ  nd this 
hard to achieve in practice.
(v) Reorganizing the child’s day to prevent trouble
There are often trouble spots in the day which will respond to fairly simple measures. For example, putting siblings in different rooms to prevent ﬁ  ghts on getting home from school; banning TV in the 
morning until the child is dressed; and so on.
Treatment can be given individually to the parent and child

Treatment can be given individually to the parent and child 
which enables live feedback in light of the parent’s progress and the child’s response. Alternatively, group treatments with parents alone have been shown to be equally effective.
(31) Trials show that parent 
management training is effective in reducing child antisocial behaviour the short-term, with moderate to large effect sizes of 0.5 to 0.8 standard deviations, and there is little loss of effect at 1 or 3 year follow-up.
(32)
(b) Family functioning
Functional Family Therapy, Multisystemic Therapy , and Treatment 
Foster Care  aim to change a range of difﬁ  culties which impede

(32)
Foster Care  aim to change a range of difﬁ  culties which impede 
effective functioning of teenagers with conduct disorder. Functional family therapy addresses family processes which need to be present such as improved communication between parent and young per-son, reducing interparental inconsistency, tightening up on super-vision and monitoring, and negotiating rules and the sanctions to be applied for breaking them. Functional family therapy has been shown to reduce reoffending rates by around 50 per cent.
(33) Other 
varieties of family therapy have not been subjected to controlled trials for young people with conduct disorder or delinquency, so cannot be evaluated for their efﬁ  cacy.
In multisystemic therapy,
(34) the young person’s and family’s

(34) the young person’s and family’s 
needs are assessed in their own context at home and in their rela-tions with other systems such as school and peers. Following the assessment, proven methods of intervention are used to address difﬁ culties and promote strengths. Multisystemic therapy differs 
from most types of family therapy such as the Milan or systemic approach as usually practised in a number of regards. Firstly, treat-ment is delivered in the situation where the young lives, e.g. at

SECTION 9  child and adolescent psychiatry 1662
home. Secondly, the therapist has a low caseload (4–6 families) and 
the team is available 24 h a day. Thirdly, the therapist is responsible for ensuring appointments are kept and for making change happen—families cannot be blamed for failing to attend or ‘not being ready’ to change. Fourthly, regular written feedback on progress towards goals from multiple sources is gathered by the therapist and acted upon. Fifthly, there is a manual for the therapeutic approach and adherence is checked weekly by the supervisor. Several randomized controlled trial attest to the effectiveness, with reoffending rates typically cut by half and time spent in psychiatric hospitalization reduced further.
(34)
Treatment foster care is another way to improve the quality of

(34)
Treatment foster care is another way to improve the quality of 
encouragement and supervision that teenagers with conduct disorder receive. The young person lives with a foster family specially trained in effective techniques; sometimes it is ordered as an alternative to jail. Outcome studies show useful reductions in reoffending.
(35)
(c) Anger management and child interpersonal skills
Most of the programmes to improve child interpersonal skills derive from cognitive behaviour therapy. A typical example is the Coping Power  Programme.
(36) This and other programmes have in 
common, in training the young person to:
  i) slow down impulsive responses to challenging situations by 
stopping and thinking,
  ii) recognize their own level of physiological arousal, and their 
own emotional state,
iii) recognize and deﬁ  ne problems,
 iv) develop several alternative responses,  v) choose the best alternative based on anticipation of 
consequences,

 vi) reinforce himself for use of this approach.Over the longer-term they aim to increase positive social 
behaviour by teaching the young person to:
 i) learn skills to make and sustain friendships,
 ii) develop so cial interaction skills such as turn-taking and 
sharing,
iii) express viewpoints in appropriate ways and listen to others.
Typically, given alone, treatment gains with interpersonal skills 
training are good within the treatment setting, but only generalize slightly to ‘real-life’ situations such as the school playground. However, when they are part of a more comprehensive programme which has those outside the young person reinforcing the approach, they add to outcome gains.
(36)
(d) Difﬁ  culties at school
These can be divided into learning problems and disruptive

(36)
These can be divided into learning problems and disruptive 
behaviour. There are proven programmes to deal with speciﬁ  c learn-
ing problems such as speciﬁ  c reading retardation, such as. reading 
recovery. However, few of the programmes have been speciﬁ  cally 
evaluated for their ability to improve outcome in children with con-duct disorder, although trials are in progress. Preschool education programmes for high risk populations have been shown to reduce arrest rates and improve employment in adulthood (see below).
There are several schemes for improving classroom behaviour, 
which vary from those which stress improved communication such as ‘circle time’ , and those which work on behavioural principles or 
are part of a multimodal package. Many of these schemes have been shown to improve classroom behaviour, and some speciﬁ  cally 
target children with conduct disorder.
(37)
(e) Peer group inﬂ  uences

(37)
A few interventions have aimed to reduce the bad inﬂ  uence of 
deviant peers. However, a number attempted this through group work with other conduct disordered youths, but outcome studies showed a worsening  of antisocial behaviour. Current treatments 
therefore either see youths individually try to steer them away from deviant peers, or work in small groups (say 3–5 youths) where the therapist can control the content of sessions. Some interventions place youths with conduct disorder in groups with well-functioning youths, and this has led to favourable outcomes.
(38)
(f) Medication for coexistent hyperactivity

(38)
Where there is comorbid hyperactivity in addition to conduct disorder, several studies attest to a large (effect size of 0.8 standard deviations or greater) reduction in both overt and covert antisocial behaviour,
(39) both at home and at school. However, the impact on 
long-term outcome is unstudied.
Engagement of the family is particularly important for this group of children and families as dropout from treatment is high, at around 30–40 per cent. Practical measures such as assisting with transport, providing childcare, holding sessions in the evening, or at other times to suit the family will all help. Many of the parents of children with conduct disorder may themselves have difﬁ  culty with

authority and officialdom and be very sensitive to criticism. Therefore the approach is more likely to succeed if it is respectful of their point of view, does not offer overly prescriptive solutions, and does not directly criticize parenting style. Practical homework tasks increase changes, as do problem-solving telephone calls from the therapist between sessions.
Parenting interventions may need to go beyond skill development 
to address more distal factors which prevent change. For example, 
drug or alcohol abuse in either parent, maternal depression, and a 
violent relationship with the partner are all common. Assistance in claiming welfare and beneﬁ  ts and help with ﬁ  nancial planning may 
reduce stress from debts.
A multimodal approach is likely to get larger changes. Therefore

A multimodal approach is likely to get larger changes. Therefore 
involving the school in treatment by visiting and offering strategies for managing the child in class is usually helpful, as is advocating for extra tuition where necessary. If the school seems unable to cope despite extra resources, consideration should be given to moving the child to a different school which specializes in the management of behavioural difﬁ  culties. Avoiding antisocial peers 
and building self-esteem may be helped by getting the child to attend after school clubs and holiday activities.
Where parents are not coping or a damaging abusive relation-

ship is detected, it may be necessary to liaise with the social services department to arrange respite for the parents or a spell of foster care. It is important during this time to work with the family to increase their skills so the child can return to the family. Where there is permanent breakdown, long-term fostering, or adoption may be recommended.

1663 9.2.5 conduct disorders in childhood and adolescence
Opportunities for prevention
Conduct disorder should offer good opportunities for prevention 
since:
1 it can be detected early reasonably well,2 early intervention is more effective than later,3 there are a number of effective interventions.
In the United States of America, a number of comprehensive 
interventions based on up to date empirical ﬁ  ndings are being 
carried out. Perhaps the best known is Families and Schools T ogether.
(40) Here the most antisocial 10 per cent of 5–6 year olds in 
schools in disadvantaged areas were selected, as judged by teacher and parent reports. They were then offered intervention which was given for a whole year in the ﬁ  rst instance and comprised:
 i) weekly parent training in groups with videotapes

i) weekly parent training in groups with videotapes
  ii) an interpersonal skills training programme for the whole classiii) academic tutoring twice a week iv) home visits from the parent trainer  v) a pairing programme with sociable peers from the class.
Almost 1000 children were randomized to receive this condition

Almost 1000 children were randomized to receive this condition 
or controls, and the project has cost over $50 million. However, so far, preliminary reports of outcome have been limited with no improvement of antisocial behaviour at home on questionnaire measures and modest improvements in the classroom. There are a number of possible reasons for the smaller effects compared to those obtained in trials with clinically referred populations. The motivation of families may be less as they don’t perceive they have a problem; starting levels of antisocial behaviour are lower, so there is not so far to go to reach normal levels; and keeping up the quality of the intervention across several sites is harder. It remains to be seen whether longer-term effects will be greater.
In the United States of America, preschool education pro-
grammes for disadvantaged children have shown good outcomes 
in small demonstration projects, but replication on a larger scale

in small demonstration projects, but replication on a larger scale 
has generally proved rather disappointing. In the United Kingdom, the government stressed the importance of helping parents of children in the ﬁ  rst 3 years of life and put substantial resources 
(£540 million) into SureStart  centres in speciﬁ  cally targeted high 
risk neighbourhoods to support parenting. Early evaluation of outcome showed no change on 24 of 25 variables; maternal accep-tance of the child was the only measured outcome to change, child antisocial behaviour did not.
(41) Separate from conduct disorder 
prevention but related is crime prevention, which can include reducing the opportunities for antisocial behaviour by tighter policing, reducing access to drugs and guns, and so on.

Much is known about the risk factors leading to conduct disorder and effective treatments exist. The challenge is to make these avail-able on a wide scale, and to develop approaches to prevention which are effective and can be put into practice at a community level.
T o access the US Federal Government’s site National Y outh Violence 
Prevention Resource Center which has recent research ﬁ  ndings, visit 
http://www.safeyouth.org/scripts/index.aspT o access the US Surgeon Generals’ thorough report on youth violence, visit 
http://www.surgeongeneral.gov/library/youthviolence/
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and conduct problems: best practices for intervention . Guilford Press, 
New Y ork.

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adolescents: research and treatment . Guilford Press, New Y ork.
Essau, C. (2003). Conduct and oppositional deﬁ  ant disorders: epidemiology, 
risk factors and treatment . Lawrence Erlbaum Associates, Mahwah, 
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and adaptation, Vol. 3 (2nd edn) (eds. D. Cicchetti and D.J. Cohen), 
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manual of mental disorders––DSM IV-R  (4th edn), text revision. 
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difﬁ culties questionnaire and the child behaviour checklist: is small 
beautiful? Journal of Abnormal Child Psychology ,27, 17–24.

6. Goodman, R. and Scott, S. (1999). Comparing the strengths and 
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association between reading achievement and antisocial behaviour: 
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conduct: nosological issues and comorbidity. In Conduct disorders in 
childhood and adolescence  (eds. J. Hill and B. Maughan). Cambridge 
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10. Collishaw, S., Maughan, B., Goodman, R., et al. (2004). Time trends in 
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11. Pullatz, M. and Bierman, K.L. (2004). Aggression, antisocial behaviour, 
and violence among girls: a developmental perspective . Guilford Press, 
New Y ork.
12. Kim-Cohen, J., Caspi, A., Taylor, A., et al. (2006) .MAOA, maltreatment, 
and gene-environment interaction predicting children’s mental health: 
new evidence and a meta-analysis. Molecular Psychiatry, 11, 903–913.
13. Brennan, P .A., Grekin, E.R., and Mednick, S.A. (2003). Prenatal and 
perinatal inﬂ  uences on conduct disorder and serious delinquency. In 
Causes of conduct disorder and delinquency  (eds. B. Lahey, T.E. Mofﬁ  tt, 
and A.Caspi), pp. 319–44. Guilford Press, New Y ork.
14. Keenan, K. and Shaw, D.S. (2003). Starting at the beginning: exploring 
the etiology of antisocial behaviour in the ﬁ  rst years of life. In Causes

the etiology of antisocial behaviour in the ﬁ  rst years of life. In Causes 
of conduct disorder and delinquency  (eds. B. Lahey, T.E. Mofﬁ  tt, and 
A.Caspi), pp. 153–81. Guilford Press, New Y ork.
15. Hill, J. (2002). Biological, psychological and social processes in the 
conduct disorders. Journal of Child Psychology and Psychiatry ,43,
133–64.
16. Lynam, D.R. and Henry, W. (2001). The role of neuropsychological 
deﬁ cits in conduct disorders. In Conduct disorders in childhood and 
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17. Ortiz, J. and Raine, A. (2004). Heart rate level and antisocial behaviour 
in children and adolescents: a meta-analysis. Journal of the American 
Academy of Child and Adolescent Psychiatry ,43, 154–62.
18. Dodge, K. (2006). Translational science in action: hostile attributional 
style and the development of aggressive behaviour problems.Development and Psychopathology, 18, 791–814.
19. Coie, J.D. (2004). The impact of negative social experiences on the 
development of antisocial behaviour. In Children’s peer relations: from 
development to intervention  (eds. J.B. Kupersmidt and K.A. Dodge), 
pp. 243–67. American Psychological Association, Washington, DC.
20. Mofﬁ  tt, T.E. (2005). Genetic and environmental inﬂ  uences on 
antisocial behaviours: evidence from behavioural-genetic research. Advances in Genetics ,55, 41–104.
21. Moss, E., Smolla, N., Cyr, C., et al. (2006). Attachment and behaviour

21. Moss, E., Smolla, N., Cyr, C., et al. (2006). Attachment and behaviour 
problems in middle childhood as reported by adult and child informants. Development and Psychopathology ,18, 425–44.
22. Patterson, G.R. (1982). Coercive family process . Castalia Publishing 
Company, Eugene, OR.
23. Rutter, M., Giller, H., and Hagell, A. (1998). Antisocial behaviour by 
young people . Cambridge University Press, Cambridge.
24. Jaffee, S.R., Mofﬁ  tt, T.E., Caspi, A., et al. (2003). Life with (or without) 
father: the beneﬁ  ts of living with two biological parents depend on the 
father’s antisocial behavior. Child Development ,74, 109–26.
25. Cummings, E.M. and Davies, P . (2002). Effects of marital conﬂ  ict on 
children: recent advances and emerging themes in process-oriented research. Journal of Child Psychology and Psychiatry ,43, 31–64.

26. Fergusson, D.M., Horwood, L.J., and Lynskey, M.T. (1996). Childhood 
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27. Jaffee, S.R., Caspi, A., Mofﬁ  tt, T.E., et al. (2004). The limits of child 
effects: evidence for genetically mediated child effects on corporal punishment, but not on physical maltreatment. Developmental 
Psychology ,40, 1047–58.
28. Champion, L., Goodall, G., and Rutter, M. (1995). Behavioural 
problems in childhood and stressors in early adult life: a 20 year follow-up of London school children. Psychological Medicine ,25, 231–46.
29. Laub, J. and Sampson, R. (2003). Shared beginnings, divergent lives: 
delinquent boys to age 70 . Harvard University Press, Cambridge, MA.

30. Scott, S. (2008). Parenting programs. Chapter in Rutter’s child and 
31. Scott, S., Spender, Q., Doolan, M., et al. (2001). Multicentre controlled 
trail of parenting groups for child antisocial behaviour in clinical 
practice. British Medical Journal ,323, 194–7.
32. Scott, S. (2005). Do parenting programmes for severe child antisocial 
behaviour work over the longer term, and for whom? 1 year follow 
up of a multi-centre controlled trial. Behavioural and Cognitive 
Psychotherapy ,33, 1–19.
33. Alexander, J.F., Holtzworth-Munroe, A., and Jameson, P .B. (1994). The 
process and outcome of marital and family therapy research: review and evaluation. In Handbook of psychotherapy and behaviour change

(eds. A. E. Bergin and S. Garﬁ  eld), pp. 595–630. Wiley, New Y ork.
34. Curtis, N.M., Ronan, K.R., and Borduin, C.M. (2004). Multisystemic 
therapy: a meta-analysis of outcome studies. Journal of Family 
Psychology ,18, 411–19.
35. Eddy, J.M., Whaley, R.B., and Chamberlain, P . (2004) .The prevention 
of violent behavior by chronic and serious male juvenile offenders: a 
2-year follow-up of a randomized clinical trial. Journal of Emotional 
and Behavioral Disorders, 12, 2–8.
36. Lochman, J.E. and Wells, K.C. (2004). The coping power program for 
preadolescent aggressive boys and their parents: outcome effects at the 1-year follow-up. Journal of Consulting and Clinical Psychology, 
72, 571–8.
37. Durlak, J. (1995). School-based prevention programs for children and

72, 571–8.
37. Durlak, J. (1995). School-based prevention programs for children and 
adolescents . Sage, Thousand Oaks, CA.38. Feldman, R. (1992). The St Louis experiment: effective treatment of 
antisocial youths in prosocial peer groups. Preventing antisocial behaviour(eds. J. McCord and R. Tremblay), pp. 233–52. Guilford Press, New Y ork.
39. Connor, D.F., Glatt, S.J., Lopez, I.D., et al. (2002). Psychopharmacology 
and aggression. I. A meta-analysis of stimulant effects on overt/covert aggression-related behaviors in ADHD. Journal of the American 
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40. Conduct Problems Prevention Research Group. (1992). 
A developmental and clinical model for prevention of conduct disorder. Development and Psychopathology ,4, 509–27.
41. Belsky, J., Melhuish, E., Barnes, J., Leyland, A., and Romanuik, H. 
(2006). Effects of sure start local programmes on children and families: early ﬁ  ndings from a quasi-experimental, cross sectional study.

(2006). Effects of sure start local programmes on children and families: early ﬁ  ndings from a quasi-experimental, cross sectional study. 
British Medical Journal ,332, 1476–9.
9.2.6 Anxiety disorders in 
The term ‘fear’ refers to the brain state evoked by dangerous stimuli 
that are avoided because they are capable of harming the organism. The term ‘anxiety’ , in contrast, refers to the brain state evoked by ‘threats’ , stimuli that signal the possibility  of danger at some point 
in the near future. Fear and anxiety represent adaptive responses to overt dangers and threats, in that these responses typically reduce the potential for harm to the organisms. Anxiety disorders  repre-
sent conditions where the level of fear is maladaptive either because it leads to clinically signiﬁ  cant distress or impairment in function.

sent conditions where the level of fear is maladaptive either because it leads to clinically signiﬁ  cant distress or impairment in function. 
These effects can result from the production of an anxiety response in a situation not perceived as dangerous by healthy people or by the production of an extreme anxiety response in a situation that healthy people would ﬁ  nd mildly anxiety provoking.
The current chapter summarizes recent research on paediatric 
anxiety disorders. A focus on developmental aspects of anxiety is 
important since most clinically impairing forms of anxiety typi-cally begin during childhood.
(1) Moreover, childhood anxiety 
disorders show associations with a range of adult psychopatholo-gies beyond anxiety, including most prominently various mood disorders. This fact has stimulated considerable debate concerning the degree to which childhood anxiety disorders reﬂ  ect early mani-

festations of adult anxiety disorders. Separation anxiety disorder (SAD) represents the only speciﬁ  c anxiety disorder that primarily 
occurs in children and adolescents but not adults. Two other dis-orders frequently co-occur with SAD, social phobia (SOPH), and generalized anxiety disorder (GAD). The current chapter focuses speciﬁ  cally on these three conditions. The chapter also reviews in 
somewhat less detail data for speciﬁ  c phobia (SPH), a typically 
minimally impairing condition, and panic disorder (PD), a condi-tion that occurs primarily in adults.
(1) Other chapters review mate-
rial for conditions that frequently co-occur with these ﬁ  ve anxiety 
disorders. This includes major depression (see Chapter 9.2.7), obsessive–compulsive disorder (Chapter 9.2.8), and trauma-related disorders (Chapters 9.3.2). Material on SAD, SOPH, GAD, SPH,

1665 9.2.6 anxiety disorders in childhood and adolescence
and PD are reviewed in three sections. The ﬁ  rst, most detailed, 
section reviews clinical features of these disorders, including typical presentations and diagnosis. The second somewhat briefer section reviews pathophysiology, and the final section briefly reviews therapeutics.
Children presenting with symptoms of anxiety typically manifest signs of various disorders. In fact, in the clinical setting, presenta-tion with a ‘pure’ form of anxiety is relatively rare. This suggests that current classiﬁ  cations group children into categories that are 
unlikely to represent distinct pathophysiologies. Nevertheless, while the current nosology is likely to change as understandings of pathophysiology advance, current classiﬁ  cation schemes remain

unlikely to represent distinct pathophysiologies. Nevertheless, while the current nosology is likely to change as understandings of pathophysiology advance, current classiﬁ  cation schemes remain 
quite useful in that they facilitate communication among individu-als working with a child and allow clinicians to draw on research in therapeutics using a common diagnostic system. The current section describes clinical presentation of ﬁ  ve speciﬁ  c anxiety disorders, as 
deﬁ ned in the fourth edition of the Diagnostic and Statistical 
Manual  (DSM-IV). These deﬁ  nitions are similar to those used 
in the 10th edition of the International Classiﬁ  cation of Disease
(ICD-10), although ICD-10 provides single diagnosis for children 
with multiple anxiety disorders, whereas and DSM-IV provides multiple diagnoses.
(a) Separation anxiety disorder
The key feature of SAD involves presentation of anxiety related to fear that harm will befall an attachment ﬁ  gure. In severe forms,

The key feature of SAD involves presentation of anxiety related to fear that harm will befall an attachment ﬁ  gure. In severe forms, 
SAD typically presents with avoidance of situations, such as school, where separation is required. The term ‘school phobia’ had been used on occasion for these presentations, but current approaches no longer use this term. Symptoms of SAD often are severe at night, leading many children to refuse to sleep alone or at friends’ homes. Considerable research examines the relationship between child-hood SAD and adult panic disorder.
The key features of SOPH involve intense fear or anxiety in situa-tions where the individual is scrutinized. This presents either as extreme form of pervasive shyness or as extreme fear in particular social situations, such as during class presentations. SOPH can also be classiﬁ  ed as a ‘generalized subtype’ , indicating that most social

situations are feared. The condition can markedly interfere with function by leading children to avoid important academic exercises that must be performed in social settings or by markedly impacting on social development. This effect on social relationships has led to some controversy concerning the boundaries between SOPH and pervasive developmental disorders (PDD). Classically, this distinc-tion can be made based on the presence of language dysfunction and stereotypic behaviour in PDD but not SOPH. Considerable research examines the relationship between late-childhood SOPH 
and early-childhood temperament.
The key feature of GAD involves a pervasive sense of worry about 
various events or circumstances. For example, children with GAD frequently worry about their competence, as might manifest on school or athletic performances. These worries are associated with other symptoms, such as muscle tension or other somatic

complaints, irritability, and trouble sleeping. Because children with SAD and SOPH also present with worry, clinicians face difﬁ  culties 
when attempting to determine if worries reﬂ  ect aspects of these 
disorders or another problem. GAD is diagnosed only when 
worries cannot be accounted for by another diagnosis. Considerable research examines the relationship between GAD and major depressive disorder (MDD).
(d) Speciﬁ  c phobia
The key feature of SPH involves fear of a speciﬁ  c stimulus or object. 
SPH can manifest to a range of objects, such as potentially dangerous animals or natural scenarios, and SPH can be categorized into one of ﬁ  ve types, based on the content of the fear. Children rarely

present for clinical care when they suffer from SPH in the absence of another anxiety disorder, despite the fact that SPH does present relatively commonly in pure forms in the community. This sug-gests that SPH typically is associated with relatively mild degrees of distress and impairment, unless SPH is associated with another anxiety disorder.
(e) Panic disorder
The key feature of PD involves spontaneous panic attacks. The term ‘panic attack’ refers to crescendo paroxysms of severe anxiety that occur suddenly and are associated with somatic and cognitive sensations, such as rapid heart beat, shortness of breath, and a strong desire to ﬂ  ee. Panic attacks occur in many situations and 
with various clinical syndromes. The key feature of PD is that at least some of these attacks occur in the absence of any cue or trigger. As such, the patient cannot attribute the attack to fear of any speciﬁ  c circumstance. PD virtually never occurs prior to puberty,

and the disorder is also very rare before adulthood.
The assessment for anxiety involves input from multiple sources. Clearly obtaining information directly from the patient is vital. Children with anxiety disorders may be reluctant to report the pre-cise nature of their fears. As a result, adults may be unaware of vital symptoms. On the other hand, children also often show reluctance to acknowledge their anxiety, either because they are unaware of their degree of incapacitation or because they are highly embar-rassed about their symptoms. In this instance, adults provide vital information concerning speciﬁ  c objects or situations that might be 
feared by children or adolescents.
Various forms of standardized assessment are available for 
paedi atric anxiety.
(2) This includes rating scales that can be directly

(2) This includes rating scales that can be directly 
completed by parents, teachers, or children, as well as scales that are completed by clinicians based on their interview of the child and parent. Moreover, standardized observational batteries typi-cally are used for the assessment of temperament, in very young children, that relate to anxiety disorders in older children. T emperament also can be measured by parent or self-report.
(3) In 
general, while high scores on various rating scales does provide some indication regarding the presence of an anxiety disorder, structured psychi atric interviews, completed by a trained clinician, represents the gold standard for arriving at a diagnosis.
Prevalence and demographics
As a group, paediatric anxiety disorders probably represent the most common form of developmental psychopathology. It is

SECTION 9  child and adolescent psychiatry 1666
 difﬁ cult to provide precise data concerning their overall prevalence, 
as the rate of anxiety disorders is highly variable across studies, most likely due to variations in assessment. Rates of anxiety disor-ders are unusually sensitive to even subtle changes in assessments of impairment.
(4) In general, overall lifetime rates of paediatric 
anxiety probably fall in the 10–20 per cent range.(5) Rates of indi-
vidual disorders vary with age. Thus, SAD represents the most common condition, with prevalence typically in the 5 per cent range, before puberty, whereas GAD and SOPH become more prevalent during adolescence, again with rates in the 5 per cent range. Rates of SPH are highly variable, depending on the strin-gency of impairment criteria, with some estimates surpassing 20 per cent. As noted above, PD is very rare before late adolescence.
In terms of demography, anxiety disorders show a strong female

In terms of demography, anxiety disorders show a strong female 
predominance. This gender difference manifests for all of the conditions examined here, and, unlike data for MDD, it emerges before puberty. While the overall rate of anxiety disorders changes relatively little from childhood to adolescence, the nature of disor-ders does change. Thus, SAD is most common in young children, 
whereas SOPH is most common in adolescence. Data concerning 
associations with social class appear somewhat mixed. While some inconsistent reports note higher rates among individuals in the relatively lower social strata, the data appear most consistent for SPH, with weaker or absent associations in other conditions.
(1)
Consistent with weak relationships, recent work suggests that abrupt changes in family economics do not lead to changes in rates of anxiety disorders, despite strong associations with changing rates of other disorders.
(6)

(6)
Data concerning comorbidity reveal distinct trends in the clinic relative to the community, most likely due to the effects of referral biases on data from the clinic. Thus, in the clinic, paediatric anxiety disorders have been linked to virtually every form of psychopatho-logy. This includes mood disorders, behaviour disorders, attention deﬁ cit hyperactivity disorder, and substance use disorders. In the 
community, however, associations appear particularly strong with a more restricted group of conditions. The most common comorbid-ity represents associations with other anxiety disorders, with odds ratios typically appearing in the three-to-ﬁ  ve range.
(1) Associations 
between SOPH and GAD appear particularly strong in this work. Comorbidity with mood disorder, particularly MDD, is only slightly weaker than comorbidity among the anxiety disorders.
(7) Other 
forms of psychopathology show far weaker associations.
Clinical course

(7) Other 
Paediatric anxiety disorders predict an increased risk for a range of adverse psychiatric outcomes in adults. This includes most promi-nently risk for adult anxiety disorders and MDD.
(1,8) In general, 
children and adolescent with one or another anxiety disorder face a two- to ﬁ  ve-fold increased risk for adult anxiety or MDD. These 
relationships reﬂ  ect the fact that most adults with various forms of 
mood or anxiety disorder show the initial signs of their problem during childhood or adolescence, manifest as a paediatric anxiety disorder. However, the overall magnitude of these longitudinal relationships between paediatric anxiety and any form of adult psychopathology appears somewhat weaker than longitudinal  relationships for other developmental psychopathologies, such as the behaviour disorders.
(9)Relatively few studies consider the long-term outcome of the spe-

ciﬁ c paediatric anxiety disorders. In the few studies that do examine 
this issue, the overall weight of the evidence suggests that risk for poor outcome is similar among all paediatric anxiety disorders.
(5)
However, some inconsistent data do note speciﬁ  c associations 
among individual child and adult disorders. For example, some evi-dence documents a particularly strong association between paediat-ric GAD and adult MDD,
(1) though studies following adolescents 
into their 30s suggest a comparable risk for MDD in adolescent SOPH.
(8) Similarly, some studies note an association between child-
hood SAD and adult PD, but the overall weight of the evidence does not provide strong support for this link.
(10) Finally, some inconsis-
tent evidence also suggests that the outcome of paediatric SPH appears relatively good, as compared with other anxiety disorders.
Neuroscience and fear

Work on the pathophysiology of anxiety disorders beneﬁ  ts from a 
wealth of research examining brain regions involved in fear and anxiety among rodents and non-human primates.
(11) Data also 
document strong cross-species parallels in the effects of threats and danger on behaviour, physiology, and information processing. This suggests that neural circuits implicated in fear and anxiety among rodents or non-human primates are likely involved in fear and anxiety among humans.
Basic science work delineates a distributed neural circuit engaged

Basic science work delineates a distributed neural circuit engaged 
by various forms of dangerous or threatening stimuli. This includes stimuli recognized as dangerous through learning, as classically studied in the ‘fear conditioning’ paradigm, whereby a neutral conditioned stimulus is paired with an aversive unconditioned stimulus.
(12) This also includes stimuli innately recognized as 
dangerous, even in the absence of prior training.(13) Finally, work 
in immature rodents and non-human primates demonstrates strong developmental inﬂ  uences on the neural circuitry associated 
with both learned and innate fears.
(11) Speciﬁ  cally, in immature 
relative to mature organisms, both genetic and environmental manipulations show the capacity to exert more robust, long-standingeffects on anxiety and fear-related behaviours as well as the under-lying neural circuitry mediating these behaviours.
Figure 9.2.6.1 illustrates the core components of the underlying

Figure 9.2.6.1 illustrates the core components of the underlying 
circuitry associated with fear and anxiety. The amygdala represents a hub in the fear circuit. As shown in Fig. 9.2.6.1, this collection of nuclei lies within the medial temporal lobe, where it receives input from various sensory cortices as well as brain-stem monoamine systems, and where it sends output to the hypothalamus and other structures that orchestrate the organism’s response to danger. While some debate continues concerning the precise role played by the amygdala in fear, the structure has been implicated in both learned 
and innate fears as well as various positive-valence emotions. Some 
data suggest that the amygdala plays a vital role in regulating atten-tion when organisms learn to associate neutral stimuli with salient events.
Fear and anxiety represent complex states that reﬂ  ect inﬂ  uences

Fear and anxiety represent complex states that reﬂ  ect inﬂ  uences 
from other brain regions beyond the amygdala. Figure 9.2.6.1 shows the location of two particularly important regions. Thus, the hippocampus also plays a role in fear and anxiety, with data most clearly implicating this brain region in the representation of spatial

1667 9.2.6 anxiety disorders in childhood and adolescence
contexts associated with threat. As shown in Fig. 9.2.6.1, the hippo-
campus lies posterior to the amygdala in the medial temporal lobe. Various components of the prefrontal cortex (PFC) also are involved in fear and anxiety. As shown in Fig. 9.2.6.1, particularly strong associations occur with ventral PFC, including both lateral and medial expanses. PFC is thought to play a regulatory role for fear and anxiety responses, serving to delineate the temporal con-text where fear and anxiety are either necessary or not appropriate, given the organism’s goals.
Familial aggregation and genetics
Most complex behaviours, including fear and anxiety, represent phenomena that result from inﬂ  uences of both genes and the

Most complex behaviours, including fear and anxiety, represent phenomena that result from inﬂ  uences of both genes and the 
environment. The associations of genes and the environment with anxiety can be examined directly with behavioural indicators of anxiety or psychiatric diagnosis. Alternatively, these associations can be examined with constructs beyond symptoms that show closer relationships to brain function. The term ‘endophenotype’ has been used to describe such underlying constructs linked to both disorders and their underlying risks.
(14)
Family studies consistently demonstrate strong associations 
among various anxiety disorders in parents and anxiety disorders in their children. More than 10 studies show that children born to parents with PD, SOPH, or GAD face a two- to four-fold incre ased risk for anxiety disorders.
(5) As with data from longitudinal studies, 
some non-speciﬁ  city emerges in other family studies. Children

some non-speciﬁ  city emerges in other family studies. Children 
born to parents with MDD even in the absence of anxiety face the same elevated risk for paediatric anxiety as children born to par-ents with anxiety disorders. These data are consistent with a wealth of data among adults documenting strong familial associations.
(15)
These ﬁ  ndings on familial aggregation might reﬂ  ect the effects of 
either genes or the environment. Data from twin and adoption studies suggest that genes account for approximately 40 per cent of the risk for anxiety both among children and adults.
(5,15)  Much like 
for longitudinal and family aggregation studies, twin studies suggest pathophysiologic similarities in the genetics of anxiety and depression. In particular, GAD and MDD appear to share many of the same genes.
(16) In terms of speciﬁ  c genes, the ﬁ  eld has only 
begun to examine associations with speciﬁ  c paediatric anxiety

begun to examine associations with speciﬁ  c paediatric anxiety 
disorders. While considerable enthusiasm pertains to research on serotonin-related genes, this enthusiasm emerges predominantly from studies in adults.
(11)
The effects of genes on risk for paediatric anxiety are not thought 
to moderate overt symptomatic expressions. Rather, genes, either as main effects or through interactions with the environment, are hypothesized to produce disruptions in the underlying function of the neural circuit illustrated in Fig. 9.2.6.1. These dis-ruptions are expected to produce perturbations in physiologic regulation and information processing functions, examples of endophenotypes for paediatric anxiety disorders. Work on endo-phenotypes in paediatric anxiety disorders generally focus on three related proﬁ  les.
First, considerable work examines variations in children’s

First, considerable work examines variations in children’s 
temperaments, as they relate to both parental histories of anxiety as well as children’s risk for anxiety, manifest later in life. This work shows that children who react with fear and hesitation in novel 
social scenarios face a high risk for anxiety.
(3) This temperamental 
classiﬁ  cation is known as ‘behavioural inhibition’ . Some evidence 
suggests that these associations pertain particularly strongly to the association with later-life SOPH.
Second, other work examines associations with variations in

Second, other work examines associations with variations in 
physiologic or cognitive responses to various threats. While various forms of fear and anxiety produce robust changes in autonomic physiology, inconsistent data document strong associations between individual differences in anxiety among humans and the magnitude of these physiological responses. Particularly interest focuses on between-group differences in conditioned physiologic reactions, but ﬁ  ndings in this area appear weak and inconsistent.
(17)
Some of the strongest findings emerge from research on the 
startle response. This defensive reﬂ  ex shows strong cross-species

(17)
startle response. This defensive reﬂ  ex shows strong cross-species 
similarities in the degree to which it can be modulated by the presence of a threat. In general, adult anxiety disorders are characterized by enhanced startle in some contexts, though data in paediatric anxiety disorders appear inconsistent. Moreover, children born to parents with either PD or MDD also show enhanced startle responses under some circumstances.
(18,19) Other 
work focuses on biases in various cognitive processes, such as attention and memory, where associations with speciﬁ  c disorders 
generally appear stronger than for studies of physiology. Here some work suggests that perturbations in face processing predict both risk for anxiety and the presence speciﬁ  cally of paediatric 
SOPH.
(20)
Finally, perturbations in respiration have been linked most 
convincingly to the diagnosis of PD.(21) Data among adults show

SOPH.
(20)
convincingly to the diagnosis of PD.(21) Data among adults show 
these respiratory perturbations aggregate within families. Moreover, findings in children and adolescents show that respiratory perturbation is associated with SAD but not other paediatric anxiety disorders, such as SOPH. Given evidence of familial aggre-gation between parental PD and childhood SAD, these data suggest that respiratory perturbation may confer a familial risk for panic disorder. Neverthe less, data examining respiratory function in off-
spring of PD patients are not consistent with this possibility.
(22)
Stress
Work in animal models demonstrates strong relationships between exposure to various forms of physical or emotional stress Fig. 9.2.6.1 Displays key anatomical components of brain circuitry engaged

Work in animal models demonstrates strong relationships between exposure to various forms of physical or emotional stress Fig. 9.2.6.1 Displays key anatomical components of brain circuitry engaged 
when various organisms encounter threats or dangers. Functional aspects of this circuitry show strong cross-species conservation, and Figure 9.2.6.1 depicts the location in the human brain of three particularly important neural structures: the ventral prefrontal cortex (PFC), amygdala, and hippocampus.

SECTION 9  child and adolescent psychiatry 1668
and individual differences in anxiety or fear.(11) These associations 
appear particularly strong in juvenile organisms. For studies among children and adolescents, strong associations also emerge with various measures of stress including either stress that occurs within the family or in other social contexts.
(23) Nevertheless, it remains 
unclear the degree to which these association reﬂ  ect speciﬁ  c conne-
ctions with anxiety, given that stress is associated with a range of other psychopathologies besides anxiety.
(24) Moreover, conside-
rable heterogeneity exists in terms of the relationship between stress and anxiety, given that some individuals exposed to extreme stress are resilient, whereas other individuals exposed to mild stress develop anxiety. At least some of these individual differences are though to reﬂ  ect the inﬂ  uences of genes on underlying neural

circuitry, such that the development of paediatric anxiety reﬂ  ects 
inﬂ uences of gene–environment interactions.
(11)
Through studies of brain imaging, it is now possible to examine 
associations between paediatric anxiety disorders and perturba-tions in brain structure or function. Relatively few brain-imaging studies have examined paediatric anxiety disorders, and the few studies that do focus on neural structures depicted in Fig. 9.2.6.1.
Without question, the amygdala stands as the most frequently 
investigated brain structure in paediatric anxiety. Two studies examine amygdala morphometry in paediatric anxiety disorders, with one of these studies reporting reduced volume and the other reporting enlarged volume, both focusing mostly on children with GAD.
(25,26)  Such inconsistencies are consistent with mophometry

(25,26)  Such inconsistencies are consistent with mophometry 
studies in adults, where inconsistent evidence of amygdala enlarge-ment or reduction emerges across a range of studies. Two other studies use functional magnetic resonance imaging (fMRI) to examine amygdala function in paediatric anxiety disorders.
(27,28)
Here, the ﬁ  ndings are more consistent, much like in a larger series 
of studies in adults. Speciﬁ  cally, both studies reported enhanced 
amygdala activation in paediatric GAD, consistent with data in adult SOPH, MDD, as well as post-traumatic distress disorder or behavioural inhibition. Finally, imaging work focused on other structures documents abnormalities with less consistency. This includes structural and functional studies of the PFC and hippocampus.
(5)
Therapeutics

(5)
A range of approaches has been suggested as useful in the treat-ment of paediatric anxiety disorders. The current chapter restricts considerations to a review of modalities studied with the rando-mized controlled trial (RCT). Two modalities have been studied in sufficient detail to provide conclusions on efficacy: cognitivebehavioural psychotherapy treatment (CBT) and selective sero-tonin reuptake inhibitors (SSRIs). The data for these two treat-ments are reviewed in most detail, whereas other treatments are mentioned only brieﬂ  y.
CBT relies on the principles of extinction, whereby an individual 
with an anxiety disorder undergoes exposure to a feared object or situation while relying on cognitive techniques taught as part of the therapy. In general, CBT is easiest when a child presents with a relatively speciﬁ  c set of fears and worries that allow the therapist to

work with the child to create a fear hierarchy. The child then gradu-ally undergoes exposure to situations on this hierarchy that are increasingly anxiety provoking. More than 10 studies use an RCT 
design to examine the efﬁ  cacy of CBT, and the overwhelming 
majority of these document strong efﬁ  cacy.
(5) Nevertheless, most 
of these studies compare CBT to a wait-list control condition, a condition that may actually be aversive. The few RCTs of CBT using more suitable control conditions generally ﬁ  nd weaker advantages 
for CBT. These studies suggest that CBT is a viable treatment option for any of the anxiety disorders considered in this chapter.
Five RCTs examine the efﬁ  cacy of one or another SSRI in paedi-
atric anxiety disorders, all using placebo control.
(5) As with the data 
for CBT, this work provides strong justiﬁ  cation for using SSRIs, in

for CBT, this work provides strong justiﬁ  cation for using SSRIs, in 
that robust treatment effects emerge. Moreover, these studies rely on placebo, a more credible control than in the CBT studies relying on wait-list comparison. Thus, the strength of the evidence sup-porting efﬁ  cacy is probably somewhat greater in SSRIs than it is 
for CBT. Nevertheless, serious concerns about the safety of SSRIs emerged in 2002, due to the suggestion that SSRIs were associated with an increased risk over placebo for suicidal thoughts or behaviour. This ultimately led the Food and Drug Administration to place a ‘black box’ warning on the use of SSRIs in children, a warning recently extended to adults aged 25 and younger. Given these concerns, CBT probably represents the most reason-able ﬁ  rst-line treatment for paediatric anxiety disorders. Among

children who either cannot complete a course of CBT or who fail to respond to CBT, SSRIs represent an eminently reasonable treatment.
A range of other treatments have been considered for paediatric 
anxiety disorders. These include both psychotherapies, such as dynamically oriented therapy, and medications, such as various non-SSRI antidepressants or benzodiazepines. Due to either the dearth of data on efﬁ  cacy or concerns with safety, all of these treat-
ments should be considered third-line options, after CBT and SSRIs.
The current chapter reviews data for paediatric anxiety disorders in three sections. The longest section reviews clinical characteristics of these disorders. This section describes the clinical features, demography, and outcome of paediatric anxiety disorders, the most common class of mental syndrome afﬂ  icting children and 
adolescence. The ﬁ  rst section is followed by a shorter section

adolescence. The ﬁ  rst section is followed by a shorter section 
focused on pathophysiology. Here, data on neural circuits implicated in anxiety are reviewed most comprehensively. Finally, treatment is brieﬂ  y reviewed in the third section. More detailed 
considerations of therapeutics for a range of paediatric psychiatric disorders can be found in section 9.5. This includes a discussion of both psychotherapies and medication.
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9.2.7 Paediatric mood disorders
In this chapter, we describe the nosology and epidemiology of 
paediatric unipolar and bipolar disorders, risk factors and predic-tors of course, and the evidence base for pharmacological and psy-chosocial treatments. We conclude this chapter by suggesting areas for future research.
Mood disorders may be classiﬁ  ed on three dimensions: (a) severity;

Mood disorders may be classiﬁ  ed on three dimensions: (a) severity; 
(b) course; and (c) presence or absence of mania/hypomania.(1)
Depressed children and adolescents may not describe their mood as sad, but instead as, ‘grouchy’ , ‘bored’ , ‘having no fun’ , or ‘empty’ .
(2)
The most severe depressive condition is major depression, which requires at least 2 weeks of a depressed, sad, bored, or anhedonic mood for most of the time, and four additional depressive symp-toms involving impairment in concentration, suicidal thoughts, difﬁ culty making decisions, impaired sleep and appetite, guilt, and 
a decreased sense of self-worth (Box 9.2.7.1). Patients with depres-sive symptoms, but whose clinical picture is below the threshold for major depression (so-called minor depression or depression NOS) can still show signiﬁ  cant impairment.
(3) Dysthymic disorder

(3) Dysthymic disorder 
is more chronic and intermittent than major depression, with periods of depression interspersed with normal mood, but with duration of at least 1 year (Box 9.2.7.2). Adjustment disorder with depressed 9.2.7 paediatric mood disorders

SECTION 9  child and adolescent psychiatry 1670
mood is a milder and self-limited disturbance of mood that follows 
a signiﬁ  cant life stressor (Box 9.2.7.3).
The presence of clinically signiﬁ  cant manic or hypomanic symp-
tomatology suggests bipolar spectrum disorder. The symptomato-logy of mania can be thought of as the mirror image of depression, with mood characterized by elation or grandiosity. Mania is associated Box 9.2.7.1 Criteria for the diagnosis of a major depressive 
episode
A. Five (or more) of the following symptoms have been present 
during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.
 Note : Do not include symptoms that are clearly due to a 
general medical condition, or mood-incongruent delusions or hallucinations.
1 Depressed mood most of the day, nearly every day, as indi-

Note : Do not include symptoms that are clearly due to a 
cated by either subjective report (e.g. feels sad or empty) or observation made by others (e.g. appears tearful). Note : In 
children and adolescents, can be irritable mood.
2 Markedly diminished interest or pleasure in all, or almost all, 
activities most of the day, nearly every day (as indicated by either subjective account or observation made by others).
3 Signiﬁ  cant weight loss when not dieting or weight gain 
(e.g. a change of more than 5 per cent of body weight in a month), or decrease or increase in appetite nearly every day. Note : In children, consider failure to make 
expected weight gains.
4 Insomnia or hypersomnia nearly every day.
5 Psychomotor agitation or retardation nearly every day 
(observable by others, not merely subjective feelings of

(observable by others, not merely subjective feelings of 
restlessness or being slowed down).
6 Fatigue or loss of energy nearly every day.7 Feelings of worthlessness or excessive or inappropriate 
guilt (which may be delusional nearly every day (not merely self-reproach or guilt about being sick).
8 Diminished ability to think or concentrate, or indecisive-
ness, nearly every day (either by subjective account or as observed by others).
9 Recurrent thoughts of death (not just fear of dying), recur-
rent suicidal ideation without a speciﬁ  c plan, or a suicide 
attempt or a speciﬁ  c plan for committing suicide.
B. The symptoms do not meet criteria for a Mixed Episode (see 
p. 365).
(1)
C. The symptoms cause clinically signiﬁ  cant distress or impair-

p. 365).
(1)
D. The symptoms are not due to the direct physiological effects 
of a substance (e.g. a drug of abuse, a medication (or a general medical condition (e.g. hypothyroidism).
E. The symptoms are not better accounted for by bereavement, 
i.e. after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.
(Modiﬁ  ed from APA (2000), Diagnostic and statistical manual of 
mental disorders  (4th edn), American Psychiatric Association 
Press, Washington, DC.)Box 9.2.7.2 Criteria for the diagnosis of dysthymic 
disorder
A. Depressed mood for most of the day, for more days than not,

disorder
A. Depressed mood for most of the day, for more days than not, 
as indicated either by subjective account or observation by others, for at least 2 years. Note : In children and adolescents, 
mood can be irritable and duration must be at least 1 year.
B. Presence, while depressed of two (or more) of the following:
1 poor appetite or overeating2 insomnia or hypersomnia3 low energy or fatigue4 low self-esteem5 poor concentration or difﬁ  culty making decisions
6 feelings of hopelessness
C. During the 2-year period (1 year for children or adolescents) of 
the disturbance, the person has never been without the symp-toms in Criteria A and B for more than 2 months at a time.
D. No Major Depressive Episode (see p. 356)
(1) has been present 
during the ﬁ  rst 2 years of the disturbance (1 year for children

during the ﬁ  rst 2 years of the disturbance (1 year for children 
and adolescents); that is the disturbance is not better accounted for by chronic Major Depressive Disorder, or Major Depressive Disorder, In Partial Remission. Note : There may have been a 
previous Major Depressive Episode provided there was a full remission (no signiﬁ  cant signs or symptoms for 2 months) 
before development of the dysthymic disorder. In addition, after the initial 2 years (1 year in children or adolescents) of dysthymic disorder, there may be superimposed episodes of Major Depressive Disorder, in which case both diagnoses may be given when the criteria are met for a Major Depressive Episode.
E. There has never been a Manic Episode (see p. 362),
(1) a Mixed 
Episode (see p. 365),(1) or a Hypomanic Episode (see p. 368),(1)
and criteria have never been met for Cyclothymic Disorder.

(1) a Mixed 
F. The disturbance does not occur exclusively during the course 
of a chronic Psychotic Disorder, such as Schizophrenia or Delusional Disorder.
G. The symptoms are not due to the direct physiological effects 
of a substance (e.g. a drug of abuse, a medication) or a general medical condition (e.g. hypothyroidism).
H. The symptoms cause clinically signiﬁ  cant distress or impair-
Press, Washington, DC.)

1671
with clear impairment, whereas hypomania, while associated with 
a change in functioning, does not always result in impairment per se. Bipolar individuals, especially in the paediatric age group, fre-quently do not show the classic distinct alternating manic and depressive periods found in adult bipolar patients. Instead they may either experience depression and manic symptoms simultane-ously, so-called mixed episodes, or alternations of mania and depression that may occur within a month, a week, or even a day, e.g. rapid cycling.
(4) Common symptoms of paediatric bipolar 
disorder are pressure of speech, increased energy, and decreased need for sleep. Risk-taking behaviour showing poor judgement (e.g. gambling, hypersexuality, excessive spending) and joking and excessive humour are very speciﬁ  c for paediatric bipolar disorder, 
but less common in paediatric samples. While irritability is a com-mon symptom of paediatric bipolar disorder, it is very non-speciﬁ  c

but less common in paediatric samples. While irritability is a com-mon symptom of paediatric bipolar disorder, it is very non-speciﬁ  c 
and is commonly found in many other conditions, such as depres-sion, oppositional deﬁ  ant disorder, and attention deﬁ  cit disorder. 
The DSM-IV requires a relatively long duration of mania (7 days) and hypomania (4 days) in order to meet criteria. Many paediatric patients may show the same symptom pattern but have very rapid cycling and therefore, do not meet these criteria. If altered function is present, such patients should receive a diagnosis of Bipolar 
Disorder NOS. Bipolar NOS is a common diagnosis for children 
with manic symptoms because very often, paediatric bipolar illness does not fulﬁ  l the duration criteria for mania, in part due to the 
frequency of rapid cycling conform to the classic adult patterns of distinct patterns of mania and depression.
(4) However, in children

(4) However, in children 
and adolescents, Bipolar disorder NOS does not appear to be different from Bipolar I or II with regard to impairment, rate of comorbid disorders, response to treatment, or family history of bipolar disorder, and many patients with BP-NOS upon longi-tudinal follow-up go on to develop BP-I or BP-II disorders.
(4)Individuals who have had a history of full mania plus major  depression receive a diagnosis of Bipolar I disorder, those with hypomania plus major depression receive a diagnosis of Bipolar II disorder, and those with hypomania and dysthymia receive a diag-nosis of cyclothymic disorder (see Boxes 9.2.7.4 and 9.2.7.5).
While some in the ﬁ  eld continue to raise questions about the

While some in the ﬁ  eld continue to raise questions about the 
validity of the diagnosis of paediatric bipolar disorder, the conver-gent evidence from longitudinal and high-risk studies is that there it is the essentially an earlier manifestation of the same illness as is found in adults, is highly familial, and shows a chronic and consistent course.
(4, 5)
Attention deﬁ  cit hyperactive disorder (ADHD) and 
disruptive disorders
Patients with ADHD, oppositional disorder, and conduct disorder 
are often irritable, show a low frustration tolerance, and can become demoralized due to school failure and peer rejection. However, in the absence of true depression, their mood will be restored as soon as the source of their frustration has been remedied. While both ADHD and depression are associated with poor concentration, the age of onset of ADHD is usually earlier than in mood disorders. Patients with ADHD have other accompanying difﬁ  culties such as

hyperactivity and impulsivity that are part of the depressive picture. Conversely, depressed patients will show changes in sleep, energy level, appetite, mood, and self-worth that are not part of the picture of ADHD. The symptoms of ADHD, such as poor concentration, hyperactivity, and impulsivity can also be seen in bipolar disorder but patients with ADHD rarely have concomitant hypersexuality, 
grandiosity, and decreased need for sleep.
(4, 5) However, hypersexu-
ality may also be seen in victims of sexual abuse, but in contrast with the hypersexuality of bipolar disorder, is not accompanied by clinically signiﬁ  cant grandiosity, pressure of speech, increased 
energy, and diminished need for sleep. Often, the diagnostic difﬁ  -

culty is not simply distinguishing between disruptive and mood disorders, but in the proper attribution of shared symptoms in patients with comorbidity, as is very often the case. When patients have both mood disorder and ADHD, usually the ADHD antedates the mood disorder. A diagnosis of a mood disorder can only be made when the shared symptoms, such as impaired concentration become worse in association with depressed or manic mood.
Patients with anxiety disorder may also become quite dysphoric, but when the anxiogenic situation is removed, normal mood frequently ensues. Anxiety is a frequent antecedent of paediatric depression and bipolar disorder.
(5, 6) Symptoms that are shared 
between disorders, such as difﬁ  culty with sleep, or impaired con-

centration, are attributed to the mood disorder only if they become worse with the onset of a depressed or manic mood state. Panic disorder is often comorbid with paediatric bipolar disorder.
(5)
However, it is important to distinguish between the symptoms of panic disorder, that are prominently somatic and associated with thoughts and feelings of dread, and rapid cycling and a mixed state, which are marked with mood instability and the presence of simultaneous, or rapidly alternating depressive and manic symptoms.Box 9.2.7.3 Criteria for the diagnosis of adjustment disorder with 
depressed mood
A. The development of emotional or behavioural symptoms 
in response to an identiﬁ  able stressor(s) occurring within 
3 months of the onset of the stressor(s).
B. These symptoms or behaviours are clinically signiﬁ  cant as 
evidenced by either of the following:

1 marked distress that is in excess of what would be expected 
from exposure to the stressor
2 signiﬁ  cant impairment in social or occupational (academic)
C. The stress-related disturbance does not meet the criteria for 
another speciﬁ  c Axis I disorder and is not merely an exacer-
bation of a pre-existing Axis I or Axis II disorder.
D. The symptoms do not represent bereavement.E. Once the stressor (or its consequences) has terminated, the sym-
ptoms do not persist for more than an additional 6 months.
Press, Washington, DC.)9.2.7 paediatric mood disorders

SECTION 9  child and adolescent psychiatry 1672
The use of marijuana, alcohol, or opiates can mimic the symptoms 
of depression, such as difﬁ  culty with concentration, motivation, 
low energy, and dysphoria. Amphetamine and cocaine abuse can mimic mania. Depressed and bipolar patients are at greatly increased risk of abusing substances, so that the presence of substance abuse does not rule out a mood disorder or vice versa, but in fact, should raise the suspicion of possible comorbidity.
Eating disorder

Patients with a restricting eating disorder who are nutritionally compromised may show symptoms that overlap with depression, including decreased appetite, low energy, and sad mood. Often the sadness is found in patients with anorexia who are being forced to gain or maintain weight against their will. A diagnosis of depres-sion, unless there is a clear historical precedent that antedates the eating disorder, should only be made when the nutritional status of the patient has been normalized. Bulimic disordered patients often have difﬁ  culties with impulse control that need to be differentiated 
from bipolar disorder.Box 9.2.7.4 Criteria for the diagnosis of bipolar disorder
A. Currently (or most recently) in a Manic Episode (see p. 362).(1)
B. There has previously been at least one Major Depressive 
Episode (see p. 356),(1) Manic Episode (see p. 362),(1) or 
Mixed Episode (see p. 365).(1)
C. The mood episodes in Criteria A and B are not better account-

ed for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Speciﬁ  ed.
Past or current history of a Manic Episode is characterized by:A. A distinct period of abnormally and persistently elevated, 
expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary).
B. During the period of mood disturbance, three (or more of 
the following symptoms have persisted (four if the mood is only irritable) and have been present to a signiﬁ  cant degree:
1 inﬂ  ated self-esteem or grandiosity
2 decreased need for sleep (e.g. feels rested after only 3 h of 
sleep)
3 more talkative than usual or pressure to keep talking4 ﬂ ight of ideas or subjective experience that thoughts are 
racing

sleep)
racing
5 distractibility (i.e. attention to easily drawn to unimport-
ant or irrelevant external stimuli)
6 increase in goal-directed activity (either socially, at work or 
school, or sexually) or psychomotor agitation
7 excessive involvement in pleasurable activities that have a 
high potential for painful consequences (e.g. engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
C. The symptoms do not meet criteria for a Mixed Episode (see 
p. 365).
(1)
D. The mood disturbance is sufﬁ  ciently severe to cause marked 
impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospi-talization to prevent harm to self or others, or there are psy-chotic features.

E. The symptoms are not due to the direct physiological effects of 
a substance (e.g. a drug of abuse, a medication, or other treat-ment) or a general medical condition (e.g. hyperthyroidism).
Note : Manic-like episodes that are clearly caused by somatic anti-
depressant treatment (e.g. medication, electroconvulsive therapy, light therapy, should not count toward a diagnosis of Bipolar I disorder.
(Modiﬁ  ed from APA (2000), Diagnostic and statistical manual 
of mental disorders  (4th edn), American Psychiatric Association 
Press, Washington, DC.)Box 9.2.7.5 Criteria for the diagnosis of cyclothymic disorder
A. For at least 2 years, the presence of numerous periods with 
hypomanic symptoms (see p. 368)(1) and numerous periods 
with depressive symptoms that do not meet criteria for a Major Depressive Episode. Note : In children and adolescents, 
the duration must be at least 1 year.
B. During the above 2-year period (1 year in children and

B. During the above 2-year period (1 year in children and 
adolescents), the person has not been without the symptoms in Criterion A for more than 2 months at a time.
C. No Major Depressive Episode (p. 356),
(1) Manic Episode 
(p. 362),(1) or Mixed Episode (see p. 365)(1) has been present 
during the ﬁ  rst 2 years of the disturbance.
 Note : After the initial 2 years (1 year in children and adoles-
cents) of Cyclothymic Disorder, there may be superimposed Manic or Mixed Episodes (in which case both Bipolar I disor-der and Cyclothymic Disorder may be diagnosed) or Major Depressive Episodes (in which case both Bipolar II disorder and Cyclothymic Disorder may be diagnosed).
D. The symptoms in Criterion A are not better accounted for by 
Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Speciﬁ  ed.

E. The symptoms are not due to the direct physiological effects 
of a substance (e.g. a drug of abuse, a medication) or a gen-eral medical condition (e.g. hyperthyroidism).
F. The symptoms cause clinically signiﬁ  cant distress or impair-

1673
Although there is evidence that borderline personality disorder can 
be reliably diagnosed in adolescents,(7) diagnostic convention 
requires that this diagnosis only be applied for adults. Still, there is general agreement that many adolescents, particularly those with mood disorders, have ‘borderline features’ , such as mood lability, impulsivity, suicidal thoughts and behaviour, chaotic interpersonal relationships, and risky behaviour that has a high likelihood of resulting in personal harm. Others have argued that borderline personality disorder is really a form of bipolar spectrum disorder, although family studies have not conﬁ  rmed this.
(5) Instead, the

(5) Instead, the 
high degree of overlap between personality disorder and bipolar disorder suggests that care be taken in not attributing symptoms that more appropriately are associated with a lifelong personality style to bipolar disorder. Conversely, in the presence of a clear and unremitting paediatric mood disorder, personality disorder should not be diagnosed.
Psychosis
Although rare in childhood, incipient schizophrenia can present with sad and detached mood, sleep disturbance, and social withdrawal. Psychotic symptoms that evolve in schizophrenia are more likely to be mood-incongruent. In contrast, psychosis in depression and bipolar disorder is more often, but not always, mood-congruent.
(2, 5) This is a diagnosis that often can only be 
made upon careful longitudinal follow-up. Since psychosis is often seen in youth with mood disorders, and schizophrenia is rare at this age group, any child or adolescents with psychosis needs to be

made upon careful longitudinal follow-up. Since psychosis is often seen in youth with mood disorders, and schizophrenia is rare at this age group, any child or adolescents with psychosis needs to be 
carefully assessed for the presence of a mood disorder, particularly bipolar illness.
Comorbidity is the rule, rather than the exception.(8) Anxiety disor-
der frequently antedates paediatric depression and bipolar disorder, with common precursors being social phobia and panic disorder, respectively. ADHD is frequently comorbid with both conditions. Substance abuse is often a complication of mood disorder, although this condition in turn lengthens episodes and increases the risk for recurrence.
Medical comorbidity
Medications used to treat epilepsy, inﬂ  ammatory bowel disease, and 
rheumatic and allergic disease can have profound effects on mood. Corticosteroids can induce depression or mania. Phenobarbital is associated with depression, as is use of inter feron.

(9) Moreover, 
systemic aspects of the diseases themselves may increase the risk for depression, in epilepsy, asthma, diabetes,  and thyroid illness. Oral 
contraceptives can also result in mood changes.
Descriptive epidemiology
The point prevalence of major depression in around 1–2 per cent in prepubertal samples, and between 3–8 per cent in adole scent samples.
(10) The prevalence of bipolar disorder is around 1 per cent 
in paediatric populations, although the rate of ‘soft’ bipolar dis-order, which has some, but not all of the core features of bipolar disorder, has been reported to be as high as 5 per cent in some adolescent samples.
(11) The male to female ratio is around 1:1 for

(11) The male to female ratio is around 1:1 for 
prepubertal depression, but increases to around 1:3 for depression after puberty. In contrast, the males and females have similar risk 
for bipolar disorder, regardless of pubertal status. The increased rate of depression after puberty is accounted for almost entirely by the increased risk in females, and may be related to changes in estradiol and testosterone associated with puberty.
(12) Prepubertal 
major depression is an admixture of two subtypes: one is highly familial, with a high risk for recurrence and for eventual paediatric mania, and the second with comorbid with disruptive disorders, a low risk for depressive recurrence, an association with parental criminality, substance abuse, and family discord, and a course more similar to conduct disorder than to mood disorder.
(13) A clear clin-

ical syndrome of depression has been reported in children as young as aged 3, particularly in those young children with a family history of mood disorders.
(14)
Course
Paediatric mood disorders tend to be both chronic and recurrent. While prepubertal depression comorbid with conduct disorder is likely not to be recurrent, studies of child-onset depression with a family history of depression show high rates of recurrence, with risks of recurrence of 40 per cent in 2 years, and over 70 per cent within 5 years.
(2) The average length of a depressive episode is 
around 4–6 months in community samples, and 6–8 months in clinical samples.
(15) The duration of dysthymic disorder is much 
longer, on average, around 5 years, according to one careful longi-tudinal study.
(2) In patients with comorbid dysthymic disorder and 
depression, so-called double depression, the risk for prolonged episodes and recurrence are both very high.
(2) Longer episodes

(2) Longer episodes 
are also predicted by comorbidity with substance abuse, conduct disorder, or anxiety disorder, family conflict, and parental depression.
(10, 16)
Paediatric bipolar disorder does not often present with ‘classic’ 
periods of alternating depression and mania. Instead, such patients frequently present with either a mixed state, e.g. simultaneous occurrence of depression and mania, or rapid cycling, with brief and alternating periods of depression and mania.
(4) In comparing 
the course of paediatric and adult bipolar patients, paediatric bipo-lar patients have many more episodes per year, and spend less time in remission.
(4) Consistent with these longitudinal observations are 
ﬁ ndings from adult pedigrees that age of onset in bipolar disorder

ﬁ ndings from adult pedigrees that age of onset in bipolar disorder 
appears to be familial, and that earlier age of onset is associated with higher rates of drug abuse, alcohol abuse, rapid cycling, and suicide attempts.
(17) Much of the impairment in paediatric bipolar 
disorder is associated with depressive symptoms that often never completely remit. As noted above, the adult criteria requiring 1 week and 4 days for mania and hypomania, respectively, may be overly stringent, insofar as a fairly high proportion (25 per cent) of patients below those criteria, so-called bipolar NOS, go on in longi-tudinal follow-up to develop clear Bipolar I or II disorder and 20 per cent of those with BP-II go on to develop BP-I within 2 years of follow-up.
(4) A longer period to recovery is predicted by longer 
duration of mood disorder, rapid cycling or mixed episode, psychosis, and lower SES.
(4)

(4)
Children and adolescents who present with a unipolar depressive 
disorder are at increased risk for developing a bipolar disorder, both in comparison to children without a mood disorder, and to individuals whose mood disorder has its onset in adulthood. Y oung depressed patients with a family history of bipolar disorder, who present with psychotic symptoms, and/or pharmacologically 9.2.7 paediatric mood disorders

SECTION 9  child and adolescent psychiatry 1674
induce mania or hypomania are at increased risk for developing 
paediatric bipolar disorder.(5,18)  According to one pharmacoepide-
miological study, the younger the depressed patient, the higher the risk for pharmacologically induced mania, although there was no standardized, direct assessment of manic behaviour.
(19) Additionally, 
one study suggests that paediatric bipolar patients with comorbid ADHD tolerate amphetamine as well as non-bipolar children with ADHD.
(20)
Sequelae
The most dreaded consequent of paediatric mood disorders is suicide. A unipolar depression conveys a 10–60-fold increased risk of suicide; nearly 80 per cent of adolescent suicide attempters have some form of a mood disorder.
(21) Suicide attempts may be even

(21) Suicide attempts may be even 
more frequent in paediatric bipolar disorder, with almost one-third of clinical samples showing a lifetime history of a suicide attempt. Studies in adults and adolescents that have assessed for bipolar disorder ﬁ  nd that as many as 10–20 per cent of all suicides have 
some form of bipolar spectrum disorder.
(21) Correlates of suicidal 
behaviour in both unipolar and bipolar disorder include earlier age of onset, history of abuse, comorbid disruptive and substance abuse disorders, hopelessness, mood lability, and chronic and unre-mitting course.
(21)
Other sequelae of untreated depression include educational and 
occupational under-attainment, interpersonal difﬁ  culties, obesity, 
cardiovascular disease, and alcohol and substance abuse. The effect of depression on body mass index (BMI) appears to be independent of treatment effects.
(22)
Aetiology

(22)
Aetiology
Both unipolar and bipolar disorders have a strong genetic com-ponent. The child of a unipolar depressed parent is at around 2–4 times the risk of the population to develop a depressive disor-der; this is even higher in children of parents with earlier onset (<age 20) and recurrent depression.
(23) Twin studies indicate that 
around 50 per cent of the variance in familial transmission of depressive symptoms is explained by heritable factors, and that the liability of depression and to anxiety may be co-transmitted.
(6)
There is some evidence that adolescent onset depression is more 
highly heritable than prepubertal depression.(24)
Bipolar disorder has an even stronger genetic component, with a

(6)
Bipolar disorder has an even stronger genetic component, with a 
bipolar parent conveying at least an 8-fold increased risk of bipolar spectrum disorder in children; twin studies suggest that heritable factors account for 70–80 per cent of the variance in familial trans-
mission.
(23) High-risk studies of both unipolar depression and 
bipolar disorder show the transmission of a wider phenotype, with 
increased rates of anxiety disorder being most prominent in both 
the offspring of depressed and bipolar parents.(5, 25)
Genetic linkage studies are beginning to converge on speciﬁ  c 
regions associated with depression and anxiety, with other regions 
implicated in bipolar disorder.(23) Linkage studies for early onset, 
recurrent depression suggest that there may be sex-speciﬁ  c linkage 
sites.(23)
The serotonin transporter promoter gene has a 44 bp insertion/

deletion, with the latter resulting in less vigorous transcription. Several studies have now shown an interaction between stressful life events and the less functional form of the transporter gene with regard to an increased risk for depression in adolescents and young adults.
(26) brain-derived neurotrophic factor (BDNF) is a gene that appears to protect the hippocampus system from the neurotoxic 
effects of stress. A three-way interaction between maltreatment, the less functional 5HTTLPR allele, and the met allele of the BDNF gene has been found with regard to risk for depression in children and adolescents.
(27) An association between the val66 form of 
BDNF and early onset depression has been reported.(28)
Genetic linkage studies have also identiﬁ  ed regions of interest for

Genetic linkage studies have also identiﬁ  ed regions of interest for 
bipolar disorder, although paediatric bipolar disorder per se has not been studied. In aggregate, linkage studies converge on chro-mosomal regions 6q and 8q.
(23, 29) Certain phenotypes of bipolar 
disorder have been reported, such as ‘lithium responsiveness’ , ‘alcoholism/suicidal behaviour’ , and ‘psychosis’ , with distinct areas of familial aggregation and linkage.
(17) Geller et al.(30) has reported 
in an association study of paediatric bipolar families that val66 form of BDNF is associated with the disease.
Structural changes in depression have been reported, with the 
most widely replicated result being changes in the anterior cingu-lated, an area associated with emotion regulation, in both bipolar and unipolar familial depression.
(31)
Paediatric bipolar subjects, compared to healthy controls, show

(31)
Paediatric bipolar subjects, compared to healthy controls, show 
decreased grey matter in the dorsolateral prefrontal cortex (DLPFC), cingulate cortex, and amygdale.
(32) Diffusion tensor 
imaging and magnetic resonance spectroscopy both point to alter-ations in axonal development and organization in the superior frontal (decreased white matter) and DLPFC regions (decreased levels of n-acetyl aspartate), respectively.
(33, 34)
Neurocognitive factors and emotion 
regulation
Depressed children and adolescents, relative to normal controls, 
show greater attention to, and distraction by sad stimuli, whereas normal controls are more likely to be distracted by happy stimuli.
(35)
Depressed adolescents are more vulnerable to the effects of rumi-nation and sad mood induction
(35) Depressed children and adoles-
cents may show less activation of reward-related circuitry when participating in a reward paradigm.
(36) These ﬁ  ndings are consis-

tent with earlier research showing that tendency to pessimism and rumination were risk factors for the onset of depressive symptoms, especially when confronted with stressful life events.
(35) Functional 
neuroimaging studies find alterations in amygdala activation to threat and other cognitive tasks, although the direction is not consistent across studies.
(37,38)
There is evidence that these tendencies may be present prior 
to the development of a mood disorder. The young children of mothers with a history of childhood onset depression (COD) show greater evidence of physiological distress (e.g. poor heart rate recovery after disappointment, resort to more passive waiting and less active distraction than normal controls, and show less efﬁ  cient

cognitive processing when confronted with an affectively laden cognitive task.
(39,40)  Positive reward anticipation, however, moder-
ated the relationship between parent early onset depression and child internalizing symptoms.
(41)
The extent to which negative affective bias, and difﬁ  culty with 
active coping is intrinsic versus learned is still unclear. Mothers with early onset depression are less responsive to their children’s expression of distress, tend to endorse and promote fewer emotion regulation strategies for their children, whereas maternal accuracy

1675
of recognition of their child’s emotional state was protective against 
child psychopathology.(42–44)  Taken together, these findings 
support a role in helping parents teach their children emotion regulation strategies such as distraction, emphasis on positive reward, and active coping as a means of preventing or treating depression.
(45)
There is growing consensus that paediatric bipolar disorder is associated with difﬁ  culty with attention, verbal and visuospacial 
memory, executive function, set-shifting, and recognition of facial expressions.
(32) In some studies, these ﬁ  ndings are present regard-
less of current mood state or medication(46) and some of these 
ﬁ ndings are present in the unaffected, high-risk offspring of adults 
with bipolar disorder.(47) Bias towards threat, and less activation of 
areas involved in emotion regulation in the face of frustration have also been reported.
(32) Many of these ﬁ  ndings are also reported in

(32) Many of these ﬁ  ndings are also reported in 
unipolar depression, and therefore, a direct comparison of these two conditions is needed.
Functional neuroimaging data are consistent with these ﬁ  ndings, 
with greater activation of reward-related circuitry (e.g. caudate and thalamus) and greater activation of inhibitory areas (e.g. DLPFC, anterior cingulated) when performing working memory tasks and viewing negatively valenced pictures compared to healthy controls.
(32)
Neuroendocrine/sleep
Neuroendocrine studies suggest that alterations in serotonergic and noradrenergic neurotransmission are associated with early onset unipolar depression.
(48) There are no clear ﬁ  ndings with regard to 
cortisol regulation and depression, although hypersecretion of cortisol close to the time of sleep has been reported to be related to adolescent depression.
(49) While subjective sleep complaints are

(49) While subjective sleep complaints are 
common in child and adolescent depression, polysomnographic studies have not consistently shown the decreased REM latency 
associated with depression that has been reported in adults.
(50)
Environmental risk factors
Environmental factors can also inﬂ  uence the onset and expression 
of paediatric mood disorders, often interacting with a genetic diathesis. Early abuse and neglect is a profound risk factor for depression, especially in interaction with a positive family history for mood disorder and certain genetic polymorphisms.
(26,27,51)
Family discord, substance abuse, and criminality are associated with depression in children from families at low familial risk for depression.
(52) Maternal-child conﬂ  ict shows a birectional rela-
tionship over time with regard to both parental and child mood dis order.
(53) A history of abuse is associated with an earlier age of 
onset and more prolonged and unremitting course in bipolar dis-order.

(54) Loss of a parent, close friend, or sibling is associated with 
an increased risk of depression in those children and adolescents with a pre-existing depressive diathesis.
(55) Conversely, a positive 
connection to family, school, and a pro-social peer group, can, in cross sectional studies, protect against depression and other health risk behaviours.
(56)
Assessment and monitoring
The properties of different assessment tools of mood disorder were recently reviewed.
(57, 58)  The most common interview-based  assessment for the severity of depression is the Children’s

(57, 58)  The most common interview-based  assessment for the severity of depression is the Children’s 
Depression Rating Scale, Revised (CDRS-R), a 17-item rating scale. Commonly used self-rating measures are the Children’s Depression Inventory for children and early adolescents, the Beck Depression Inventory (for adolescents and adults), the Reynolds Adolescent Depression Scale, the Center for Epidemiological Studies, Depression Scale (CES-D), and the Mood and Feelings Questionnaire (MFQ). The CDI shows treatment sensitivity, but 
does not distinguish well between anxiety and depression, and the 
CES-D does not have an item about suicidal ideation. The main advantage of the MFQ is that it has a short form for screening, has been validated in both community and clinical sites, has a parent form (so does the CDI), and can be used for both children and adolescents.

Two interview-based methods for monitoring the level of mania 
are the Y oung Mania Rating Scale and the Mania Rating Scale from the K-SADS.
(4) The advantage of the latter is that it can be taken 
from one of the most commonly used diagnostic interviews for children and adolescents. A self-report for mania also shows prom-ise, but has not yet been used in clinical trials.
(5)
Treatment and prevention
Practice guidelines recommend that the initial treatment for mild-to-moderate depression be support, education, and one of two forms of psychotherapy (cognitive behaviour therapy [CBT] or interpersonal therapy [IPT]). For patients who eschew psycho-therapy, or who live in a region where speciﬁ  c indicated forms of 
psychotherapy are not available, antidepressant medication is an 
appropriate approach. Guidelines agree that for more severe 
depression, combination of antidepressant medication and psycho-
therapy are ideal, although the data are mixed on this point

therapy are ideal, although the data are mixed on this point 
(reviewed below).
(59, 60)
Because depression is a chronic and recurrent illness, a long-term 
approach should be taken to the management of child and adoles-cent depression. Therefore, after symptomatic relief, treatment should be continued for at least 6–12 months, since there is evidence that without psychotherapy booster sessions or continued medica-tion treatment, there is a substantially increased risk of relapse or recurrence.
(59)
There is strong and convergent evidence for the efﬁ  cacy of CBT 
for adolescent depression in clinical samples, and for child depres-sion in symptomatic volunteers,
(59,61)  with a relatively modest 
effect size ( d = 0.34) relative to a waitlist condition or a comparison

effect size ( d = 0.34) relative to a waitlist condition or a comparison 
treatment. While some studies in clinical samples showed superio-rity of CBT to credible alternative treatments, the largest and most comprehensive study of the treatment of adolescent depression found that CBT was no better than placebo with regard to acute clinical response (43 per cent versus 35 per cent).
(62) In that study, 
CBT was more efﬁ  cacious than placebo in those with higher 
incomes (>$75 000) and with higher levels of cognitive distortion.(63)
While the response rate for combination (of medication and CBT) treatment was not different than for medication alone (71 per cent versus 61 per cent), combination resulted in a more rapid response and greater likelihood of remission (37 per cent versus 20 per cent) than medication alone.
(63) However, studies of combination treat-

ment for depression have been inconsistent. The addition of CBT to antidepressant treatment, both in primary care, and to the 9.2.7 paediatric mood disorders

SECTION 9  child and adolescent psychiatry 1676
management of moderately to severely ill depressed patients failed 
to improve outcome over antidepressant treatment alone.(64, 65)
A more recent study of depressed adolescents who did not respond to an adequate initial trial of an antidepressant found that the combination of medication and CBT resulted in a higher rate of improvement among subjects than medication alone.
(66)
Interpersonal therapy is a well-established treatment for adult 
depression, and more recently has been shown to be superior to waitlist control, clinical management, and treatment as usual.
(61)
This treatment has been demonstrated to be superior to treatment as usual in a community setting, as well.
(59) Other forms of treatment 
that show promise are attachment-based therapy and family psycho-education, but have not yet been replicated by other groups.
(59)
A group CBT approach that has been used for the treatment of

(59)
A group CBT approach that has been used for the treatment of 
depression,(67) has been adapted for the prevention of depression. 
In adolescents with subsyndromal depression, the group CBT resulted in a lower risk of onset of major depression than in the treatment usual group.
(67) This approach was extended to the adole-
scent offspring of depressed parents. Adolescents, in addition to having parents with a history of depression needed to have had a prior depressive episode or subsyndromal symptoms. In an initial clinical trial and one 4-site replication, the intervention resulted in a 2–5-fold lower risk for new-onset depression.
(68) The presence of 
current depression in the caregiver moderated the effectiveness of the CBT intervention, with children of parents with current depres-sion failing to show an effect from the intervention. Weissman et al.

(69) recently demonstrated that treatment of maternal depres-
sion resulted in symptomatic improvement in their children, particularly with regard to internalizing symptoms. A family psychoeducational approach has been shown to improve commu-nication and support with regard to depression in a family member, although there was no difference in the incidence of depression in this approach versus a comparison educational treatment.
(70)
The selective serotonin reuptake inhibitors (SSRIs) form the 
mainstay of medication management of depression. Fluoxetine is the only medication that is approved by the Food and Drug Administration (FDA) and the Medicines and Health care Regulatory Agency (MHRA) for use in paediatric depression, because it has the strongest evidence of efﬁ  cacy (http://www.fda.
gov and http://www.mhra.gov.uk). Other medications for which there is some evidence of efﬁ  cacy are citalopram, sertraline, and

gov and http://www.mhra.gov.uk). Other medications for which there is some evidence of efﬁ  cacy are citalopram, sertraline, and 
venlafaxine, although for each of these medications, there is some evidence that these agents are more efﬁ  cacious for adolescent than 
for child-onset depression.
(71) In contrast, ﬂ  uoxetine shows similar 
efﬁ cacy for both children and adolescents. Tricyclic antidepressants 
have been shown to be ineffective for children and adolescents with depression.
(72) One possible exception is clomipramine, that has 
been demonstrated, when given IV to reverse chronic and refrac-tory depression.
(73) While there are no controlled trials, buproprion 
is commonly used for paediatric depression, and in open trials shows evidence of efﬁ  cacy.
(74) One small controlled study suggests 
that omega-3 fatty acids may be efﬁ  cacious for the relief of child 
depression.(75)
Children and adolescents metabolize several of the antidepres-

sants more quickly (e.g. citalopram, sertraline) compared to adults, and so equal or higher doses may be required in order to achieve a similar effect.
(76) There has been little work in pharmacogenetics in 
paediatric populations, although one study has replicated adult ﬁ ndings showing that the less functional form of the serotonin transporter gene is associated with a less vigorous response to an 
antidepressant.
(77)
The use of SSRIs increased steadily over the past decade, but

(77)
The use of SSRIs increased steadily over the past decade, but 
enthusiasm for their use on the part of both families and clinicians has been curtailed by recent reports of an association between antidepressant use and the occurrence of spontaneously-reported suicidal adverse events (i.e. new-onset or worsening suicidal ideation or an attempt), which resulted in the FDA issuing a black box warning about this side effect. The FDA conducted a meta-analysis that showed on average that around 4 per cent of the drug-treated and 2 per cent of those on placebo developed a suicidal adverse event.
(78) In the subset of studies where suicidal ideation 
was measured systematically, there was no difference in suicidality by treatment condition, with a trend towards a protective effect in the medication group. A more recent meta-analysis, using random- rather than ﬁ  xed-effects modelling and including more studies that

were not available at the time of the FDAs analysis also found an increased risk, although the estimates of the risk difference for suicidal ideation and behaviour were 0.7 per cent rather than 2 per cent.
(71) In this meta-analysis, the beneﬁ  ts of antidepressants were 
also assessed, and in the case of depression, around 11 times more individuals showed clinical improvement than developed these sui-cidal adverse events, suggesting a favourable risk-beneﬁ  t ratio for 
the use of antidepressants, given careful clinical monitoring.
For patients who have been treated with psychotherapy or medi-
cation, addition of a complementary modality (e.g. psychotherapy or medication) is indicated. Family discord should be addressed by family therapy, and parental depression should be identiﬁ  ed and

cation, addition of a complementary modality (e.g. psychotherapy or medication) is indicated. Family discord should be addressed by family therapy, and parental depression should be identiﬁ  ed and 
referred for treatment. Failure to respond at that point suggests the need to try a second SSRI, followed by either venlafaxine or bupro-pion. A recent study comparing depressed adolescents who did not respond to an adequate trial with an SSRI found that a switch to second SSRI was as efﬁ  cacious as a switch to venlafaxine.
(66)
Augmentation is indicated if a patient shows a partial but palpable 
response but still is symptomatic, whereas those who have not responded at all should be tapered and switched to another medi-cation.
(79) There have been no clinical trials of augmentation in 
paediatric depressed subjects, but placebo-controlled trials in adults support the use of augmentation of SSRI treatment with lithium, T3, and bupropion.
(80) Also, for depression with a seasonal

(80) Also, for depression with a seasonal 
component, light therapy has been shown to be efﬁ  cacious in psy-
chiatric clinical trials.(81)
Paediatric bipolar disorder
Because paediatric bipolar disorder is rarer than unipolar depres-sion and because of the previous controversy about diagnosis, there has only recently been increased attention paid to its treatment. Best practice guidelines are based upon downward extension of experience in adults, as well as a handful of clinical trials, but the ﬁ eld is changing very rapidly, and it is expected that these guide-
lines will change in parallel.
(82) Paediatric bipolar disorder has

(82) Paediatric bipolar disorder has 
intrinsic in it a paradox: the most functionally impairing aspect of the condition is depression, but treatment of depression may induce mania. Therefore, treatment of paediatric bipolar disorder must be viewed as the prevention of future episodes, with an emphasis on mood stabilization, and not just on the relief of acute symptoms, important as that may be in the short-run. This idea that one needs to take medication in order to stay well, as compared to achieve symptomatic relief, is one that is difﬁ  cult for children

1677
and adolescents to grasp, and therefore needs to be an important 
target of ongoing management.
Acute management of mania
Emergent  mania represents a true emergency, as it can result in risky 
behaviour with irreversible consequences. One key to the control of mania is to restore sleep, since sleep deprivation increases mania in a vicious cycle. Most commonly, for the acute control of mania, practitioners use atypical neuroleptics such as risperdone, olanzap-ine, and quetiapine, which have been shown to be more efﬁ  cacious 
than placebo in reducing manic symptoms.
(82) Quetiapine has also 
been shown, in one study, to be superior to divalproex in reducing manic symptoms and achieving both response and remission, whereas lithium and divalproex were shown to have similar efﬁ  cacy. 
An open trial comparing the efﬁ  cacy of three mood stabilizers for

An open trial comparing the efﬁ  cacy of three mood stabilizers for 
achieving clinical response in paedi atric bipolar disorder found that divalproex was somewhat more efﬁ  cacious (ES = 0.58) compared to 
either lithium or carbamazepine (ESs = 0.38). Oxcarbazepine, a metabolite of carbamazepine, on the other hand, was found to be no better than placebo in achieving stabilization. Both for the  man-agement of psychotic symptoms and mania, the combination of a mood stabilizer such as lithium or divalproex and a neuroleptic appears to be more efﬁ  cacious in producing remission than a mood 
stabilizer alone.
(82)
Acute management of depression
For the treatment-naïve patient, the ﬁ  rst step in the management 
of the depressed bipolar patient is treatment with a mood stabili zer.
(5, 82) Open trials show that divalproex and lithium are 
relatively efﬁ  cacious as mood stabilizers, with carbamazepine being

relatively efﬁ  cacious as mood stabilizers, with carbamazepine being 
efficacious, but less so than either of the former two agents. In adults, atypical neuroleptics are also being established as mood stabilizers with potency equal to lithium and divalproex, although with very concerning side effects of rapid weight gain. Once a ther-apeutic blood level of divalproex or lithium has been attained patients often will experience a relief of their depression. Sometimes alteration in the dosage, either an increase or a decrease, can bring further symptomatic relief. If a patient is still experiencing signiﬁ  -
cant depressive symptoms, then an antidepressant can be added, but very carefully. Some data from adult studies suggests that bupropion may result in fewer manic break throughs than other antidepressants but those data do not exist yet in children.

Lamotrigine has been shown in adults to provide prophylaxis 
against future depressive episodes, but is not helpful for the treatment of acute depression; this has not yet been investigated in children, except in open trials.
(82)
Medical management
The medications used for mood stabilization all have systemic and potentially very serious side effects. The atypical neuroleptics cause rapid weight gain; therefore weight, a lipid proﬁ  le, fasting blood 
sugar, and waistline should be carefully monitored. One preliminary study suggests that concomitant treatment with metformin may attenuate weight gain.
(83) Hypoprolactinaemia and galactorrhoea 
are also consequences of neuroleptic use. Lithium is associated with thyroid disease (usually hypothyroidism), which if undetected can affect mood and treatment reponse. Lithium also can impair kidney function, resulting in an inability to concentrate urine, reduced glomerular ﬁ  tration rate, and proteinuria. Therefore, renal

function should be assessed prior to treatment and annually with a creatinine clearance and a 24 h urine for protein should be obtained at baseline and annually. Divalproex can have toxic effects on the 
hemopoetic system and the liver, both of which must be carefully 
monitored. Lamotrigine is rarely associated (0.5 per cent) with Stevens–Johnson syndrome, a disease of mucous membranes that can be potentially life-threatening.
Psychotherapeutic management
Patient and parent education and support are essential, including the importance of medication adherence, keeping regular sleep habits, avoidance of caffeine and other substances, and ability to recognize subtle signs of a shift in mood. Some speciﬁ  c forms of psychotherapy 
that target family process and emotion regulation have been developed.
(84) Family focused treatment (FFT) has been used

(84) Family focused treatment (FFT) has been used 
successful for adult bipolar disorder and results in fewer depressive episodes and better overall functioning. Pilot studies indicate what appear to be similar effects for adolescent bipolar disorder. A family psychoeducational approach also shows promise for improving adherence and reducing the risk of relapse.
(85) Two other approaches 
that have been piloted but not yet tested in randomized clinical trials are the application of CBT to paediatric bipolar disorder, which includes family education, emotion regulation, self-monitoring, and social skills training, and the adaptation of dialectic behaviour therapy (DBT) to adolescent bipolar disorder.
(86, 87)

(86, 87)
With regard to both conditions, it is important to try to understand neural circuitry and identify potential intermediate phenotypes, such as emotion dysregulation or impaired executive functioning, which are trait markers for risk for these disorders. The identi-ﬁ cation of intermediate phenotypes then opens up great opportu-
nities for monitoring treatment response, identifying youth at risk for the disorder, and conducting genetic studies on less complex phenotypes that are more likely to yield deﬁ  nitive results.
While there have been great strides in the treatment of depres-
sion, it is difﬁ  cult to predict who is going to respond to what treat-
ment, and also, who is most likely to experience side effects such as increased suicidal ideation. Pharmacogenetics and monitor-ing of biomarkers may hold promise for improving matching of patient to treatment. The best approaches to continuation and maintenance have only been addressed for the simplest cases

(e.g. uncomplicated episode with patient having a successful 
response to ﬂ  uoxetine.
(88)
Almost every aspect of treatment in paediatric bipolar disorder 
requires further study, including the best approach to the  management of mania, depression, and mixed state, testing the role of various promising psychosocial approaches, and identify-ing pharmacogenetic and biomarker predictors of treatment response.
While major depression has been described in high-risk children 
as young as age 3,
(14) it is less clear what are the earliest manifesta-
tions of paediatric bipolar disorder. Ongoing longitudinal and high-risk studies will help to clarify the answer to this question in coming years, and may then provide the basis for preventive interventions.9.2.7 paediatric mood disorders

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response and plasma levels of bupropion and metabolites in a 9.2.7 paediatric mood disorders

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Monitoring ,28, 190–8.
75. Nemets, H., Nemets, B., Apter, A., et al. (2006). Omega-3 treatment 
of childhood depression: a controlled, double-blind pilot study. The
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76. Findling, R.L., McNamara, N.K., Stansbrey, R.J., et al. (2006). 
The relevance of pharmacokinetic studies in designing efﬁ  cacy 
trials in juvenile major depression. Journal of Child and Adolescent 
Psychopharmacology ,16, 131–45.
77. Kronenberg, S., Apter, A., Brent, D., et al. (in press). Serotonin 
transporter (5HTT) polymorphism and citalopram effectiveness and 
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78. Hammad, T.A., Laughren, T., and Racoosin, J. (2006). Suicidality in 
pediatric patients treated with antidepressant drugs. Archives of General 
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1397–405.9.2.8 Obsessive–compulsive 
disorder and tics in children and adolescents

Although obsessive–compulsive disorder ( OCD ) has long been 
considered as a disorder of adulthood, the early child psychiatric literature contains famous descriptions of typical cases. At the beginning of the twentieth century, Janet reported on a 5-year-old with classical obsessive–compulsive ( OC) symptoms, and Freud 
described in his adult patients obsessional behaviours dating back from childhood, while speculating on the strong constitutional inﬂ uence in the choice of these symptoms. In the 1950’s, Kanner 
noted the resemblance and sometimes the association between compulsive movements and tics, and Despert described the ﬁ  rst

noted the resemblance and sometimes the association between compulsive movements and tics, and Despert described the ﬁ  rst 
large series of obsessive–compulsive children, noting the prepon-derance of males and the children’s perception of the abnormality and undesirability of their behaviours.
Tics have been described since antiquity, but the ﬁ  rst systematic 
reports are those of Itard, in 1825, and Gilles de la T ourette, in 1885. 
Both noted the association between tic disorders and OC symptoms, and speculated on the hereditary nature of the syndrome.
For the last two decades, there has been a tremendous growth 
of interest and research on OCD and tic disorders. Signiﬁ  cant

of interest and research on OCD and tic disorders. Signiﬁ  cant 
advances have occurred regarding the phenomenology, epidemiology, genetics, neurophysiology, pathogenesis, and treatment of both disorders. The frequent association of OCD and/or tic disorders with other neuropsychiatric disorders, as well as the increasing evidence coming from in-vivo neuroimaging studies, have led to a fascinating aspect of current neurobiological research—the possible localization of brain circuits mediating the abnormal behaviours. Of all paediatric psychiatric disorders, OCD and tic disorders now appear as model neurobiological disorders to investigate the role of genetic, neurobiological, and environmental mechanisms that interact to produce clinical syndromes of varying severity.

Obsessions are persistently recurring thoughts, impulses, or images that are experienced as intrusive, inappropriate, and distressing, and that are not simply excessive worries about realistic problems. Compulsions are repetitive behaviours or mental acts that a person feels driven to perform according to a rigidly applied rule, in order to reduce distress or to prevent some dreaded outcome. 
Obsessions and compulsions are egodystonic, i.e. there are consid-
ered by the subject himself as irrational or unrealistic, and are, at least partly, resisted. Children and adolescents with OCD may hide their symptoms, or will only allow them to appear at home, or in the presence of family members, suggesting partial voluntary control.
The clinical presentation of OCD during childhood and adoles-
cence has been documented in various cultures, with clinical series

1681
reported from the U.S., Japan, India, Israel, Denmark, and Spain.

Typically, children and adolescents with OCD experience multiple obsessions and compulsions, whose content may change over time. The most frequent obsessions in young people include fear of dirt or germs, of danger to self or a loved one, symmetry or exactness, somatic, religious and sexual obsessions. The most common com-pulsions consist of washing rituals, repeating, checking, touching, counting, ordering, and hoarding. Generally, compulsions are carried out to dispel anxiety and/or in response to an obsession (e.g. to ward off fear of harm). However, some obsessions and rituals involve an internal sense that ‘it does not feel right’ until the thought or action is completed, and certain children with OCD may be unable to specify the dreaded event that the compulsive rituals are intended to prevent, beyond a vague premonition of something bad happening. Simple compulsions, such as repetitive touching or symmetrical ordering, may even lack any discernable ideational component, and may

to prevent, beyond a vague premonition of something bad happening. Simple compulsions, such as repetitive touching or symmetrical ordering, may even lack any discernable ideational component, and may be phenomenologically indistin-guishable from complex tics. Several symptom dimensions have been identiﬁ  ed in OCD, which could suggest possible aetiologic

heterogeneity. Based on the symptom categories of the Children’s Y ale-Brown Obsessive–Compulsive Scale (CY-BOCS, the most widely used symptomatic measure in paediatric OCD research,
(1))
Stewart et al.(2) identiﬁ  ed four distinct factors, using principal 
components analysis: (1) symmetry/ordering/repeating/checking; (2) contamination/cleaning/aggressive/somatic; (3) hoarding; and (4) sexual/religious symptoms. These symptom dimensions are congruent with those described in similar studies of adults with OCD, suggesting fairly consistent covariation of OCD symptoms through the developmental course.
Tics
Tics are sudden, rapid, non-rhythmic, stereotyped, repetitive movements (motor tics) or sounds (vocal tics). They may mimic simple or more complicated fragments of normal motor or vocal behaviours, which are misplaced in context. Tics vary greatly in nature, location, number, intensity, forcefulness, and frequency.
(4, 5)

(4, 5)
Common simple motor tics are neck jerking, eye blinking, eleva-tion of shoulders, mouth movements. Common simple vocal tics include throat clearing, snifﬁ  ng, sucking air, grunting, snorting, 
humming, or barking. Complex motor tics may combine simple tics, and involve facial movements, jumping, gyrating, touching, kicking, grooming behaviours, or echokinesis (repeating someone else’s movement). They may appear to be purposive in character, as brushing hair back, or suddenly rotating on one foot to make a 360-degree turn. In a small fraction of cases, the complex motor tics are self-injuring behaviours, which may be potentially danger ous. 
Complex verbal tics include the repetition of what was just heard (echolalia) or said (palilalia), or socially inappropriate utterances (coprolalia), even disguised through sign language. The speciﬁ  c tic 
repertoire of an individual typically changes over time with no 
predictable course, but complex tics are rare in the absence of

predictable course, but complex tics are rare in the absence of 
simple tics. Tics often occur in discrete unpredictable bouts over the course of a day, separated by tic-free intervals. The combina-tion of bouts over different time scales explains why globally tics wax and wane over time.
Tics are suggestible, as indicated by their transient reappearance 
when they are recalled. They are also suppressible, as they can generally be willfully held back for brief periods of time. Tics are preceded by an inner tension, an urge to move or utter that may build-up during suppression. Suppressing tics requires mental

effort and may accentuate inattention; conversely, attentional prob-lems decrease the ability to suppress tics, and are associated with more severe tics. Various premonitory sensory urges have been reported to prompt the tics, together with feelings of inner conﬂ  icts over whether and when to yield to these urges. Sensory 
urges include focal tension, pressure, tickling, cold, warmth, pares-thesias, and generalized inner tension or anxiety. They usually arise in the part of the body involved in the subsequent motor act, and completing the tic seems to yield a temporary relief of the urge. Also, various auditory and visual cues, highly selective for each individual, can elicit tics, and some patients are extremely sensitive to these external cues, as in echo phenomena. Excitement and fatigue typically worsen tics, which are often more frequent and forceful when the individual is alone. Activities requiring ﬁ  ne

motor skills and attention improve tics. Although much dimin-ished, tics can occur during sleep, unlike many other movement disorders.
Children and adolescents with tic disorders may present a broad 
array of associated behavioural difficulties, including OC symptoms, disinhibited speech or conduct, impulsivity, distracti-bility, and motor hyperactivity.
(5) The presence of motor and/or 
phonic tics can be associated with difﬁ  culties in self-esteem, self-
deﬁ nition, family life, peer acceptance or relationships, and school 
performance.
Age of onset
The age at onset of OCD appears bimodal.(6) Prepubertal onset is 
associated with a male preponderance and an increased risk for tic disorders, including T ourette’s disorder. A second peak of onset occurs at or after puberty. Overall, the mean age at onset of OCD in children and adolescents have ranged from 9 years in referred subjects
(7) to 12.8 years in a community sample.(8)

The median onset age for simple motor tics is between 4 and 
6 years.(9) Phonic or vocal tics usually appear several years after the 
onset of motor tics, in most cases between 8 and 15 years. Many young children are completely oblivious of their tics, or experience them as wholly involuntary. Premonitory urges typically show up several years after the onset of the tics, on average around 10 years of age. Suppressibility of tics developmentally precedes awareness of premonitory urges, but may get easier as awareness increases.
(10)
Sex ratio
In community-based samples of adolescents with OCD, there are approximately equal numbers of males and females, while in most studies of referred children and youth with OCD, males outnum-ber females by 2:1 or 3:1.
(11)
Most studies show that the prevalence of tics is higher among 
boys than girls, with a ratio of 6–8:1 in clinic-based samples, and about 2:1 in community-based studies.

(11)
(12) The sex ratio generally 
increases with tic duration and severity. Thus, in one study, the ratio of boys to girls was 1.6:1 for motor tics present for 1-2 con-secutive months, increasing to 7.5:1 when tics were present for 2 non consecutive months, or more than 3 months.
(13)
In referred children and adolescents with OCD, the frequency of a diagnosis of any tic disorder ranges from 17 per cent to 40 per cent, and that of T ourette’s disorder from 11 per cent to 15 per cent.
(14)9.2.8 obsessive–compulsive disorder and tics in children and adolescents

SECTION 9  child and adolescent psychiatry 1682
Conversely, one study found that 29 per cent of T ourette’s disorder 
patients displayed OC behaviours.(15) In longitudinal studies, about 
50 per cent of children and adolescents with T ourette’s disorder develop OC symptoms or OCD by adulthood,
(16)whereas, in a 
follow-up study of children and adolescents initially treated for OCD, nearly 60 per cent were found to have a lifetime history of tics that ranged from simple, mild, and transient tics to T ourette’s disorder, for which the rate was 11 per cent.
(17) On the basis of 
personal or family history of tics, a distinction has been proposed between ‘tic-related OCD’ and ‘non-tic-related OCD’ , under the assumption that the two forms might differ in terms of clinical phenomenology, neurobiological concomitants, and responsive-ness to pharmacological interventions.
(18) Tic-related OCD appears

(18) Tic-related OCD appears 
to have an earlier onset, and to occur more frequently in boys than in girls. The need to touch or rub, blinking and staring rituals, worries over symmetry and exactness, a sense of incompleteness, and intrusive aggressive thoughts and images, are signiﬁ  cantly 
more common in tic-related OCD, whereas contamination worries and cleaning compulsions are more frequent in patients with non-tic-related OCD.
The overall lifetime psychiatric comorbidity in children and 
adolescents with OCD is about 75 per cent, both in referred and in community cases. The most common conditions comorbid with OCD are affective disorders, with prevalence ranging across studies from 8 per cent to 73 per cent for mood disorders, and from 13 per cent to 70 per cent for anxiety disorders.
(19) While occurring

(19) While occurring 
less frequently in non-referred subjects, a high rate of disruptive behaviour disorders—attention deficit/hyperactivity disorder (ADHD) and oppositional deﬁ  ant disorder—has been reported in 
subjects seen in paediatric OCD clinics. In girls, OCD can be comor-bid to anorexia nervosa.
Less than 10 per cent of clinically referred children and adoles-
cents with T ourette’s disorder do not have another morbid condition. About 55 per cent also have ADHD, and more than a third have anger control problems.
(9) Rage attacks in response to minimal

(9) Rage attacks in response to minimal 
provocation, lasting from a few minutes to an hour and usually followed by remorse, as well as an increased vulnerability for drug abuse, depression, and antisocial behaviour, are primarily observed when comorbid ADHD is present. Globally, comorbidity of T ourette’s disorder increases in adolescence, but more markedly for OCD and anxiety disorders in those without ADHD. Individuals with T ourette’s disorder have consistently shown difﬁ  culties with 
ﬁ ne motor control and visual motor integration, as well as impair-
ment in procedural or habit-based learning. Sleep is often disturbed, with increased short lasting motor activity, especially in non-REM sleep, compared to healthy controls.
Both DSM-IV and ICD-10 deﬁ  ne OCD, regardless of age, by

Both DSM-IV and ICD-10 deﬁ  ne OCD, regardless of age, by 
obsessions and/or compulsions, which are described, at some point during the course of the disorder, as excessive or unreasonable (criterion B), and are severe enough to cause marked distress or to interfere signiﬁ  cantly with the person’s normal routine, or usual 
social activities or relationships. The speciﬁ  c content of the obses-
sions or compulsions cannot be restricted to another Axis I diagno-sis, such as an eating disorder, a mood disorder, or schizophrenia. The DSM-IV adds that the disturbance is not due to the direct physiological effects of a substance or a general medical condition. The ICD-10 allows subclassiﬁ  cation of forms with predominant

obsessions, predominant compulsions, or mixed symptoms. In DSM-IV , the only difference in diagnostic criteria between children and adults appears in criterion B; although most children and adolescents actually acknowledge the senselessness of their symptoms, the requirement that insight is preserved is waived for children.
In both DSM-IV and ICD-10, tic disorders are divided into 
four categories, according to duration of the symptoms, and pres-ence of vocal tics in addition to motor tics: T ourette’s disorder, chronic motor or vocal tic disorder, transient tic disorder, and tic disorder not otherwise speciﬁ  ed (NOS). Transient tic disorder is 
deﬁ ned by single or multiple motor and/or vocal tics that occur 
many times a day, nearly everyday for at least 4 weeks, but for no 
longer than 12 consecutive months. In chronic motor or vocal tic

longer than 12 consecutive months. In chronic motor or vocal tic 
disorder, either motor or vocal tics, but not both, have been present at some time during the illness. In T ourette’s disorder, both multi-ple motor and one or more vocal tic have to be present, although not necessarily concurrently. Both T ourette’s disorder and chronic motor or vocal tic disorder have a duration of more than 1 year, with no tic-free period of more than 3 months. All tic disorders must have onset before age 18 years. In all, the disturbance causes marked distress or signiﬁ  cant impairment in social, occupational,

or other important areas of functioning, and is not due to the direct physiological effects of a substance (e.g. stimulants), or a general medical condition. The ICD-10 recognizes that there is an immense variation in the severity of tics. At the one extreme of the continuum, the presence of transient tics, at some time during childhood, is near-normal. At the other extreme, T ourette’s disorder is an uncommon, chronic, and incapacitating disorder.

In ICD-10, it is stated that OCD cannot be diagnosed if the patient meets T ourette’s disorder criteria, while both diagnoses may be given simultaneously in DSM-IV . Unlike tics, compulsions are aimed at neutralizing the anxiety resulting from an obsession, and/or they are performed according to rules that must be applied rigidly. However, both compulsive rituals and complex tics may be preceded by premonitory urges, which persist until the action is completed. In individuals with both T ourette’s disorder and OCD, these symptoms are sometimes so closely intertwined that efforts to distinguish them would be futile.
From a developmental perspective, pathological OC behaviours 
and thoughts differ from normal childhood rituals, mainly by their emotional context and their use of maladaptive versus adaptive cognitive and behavioural strategies.
(20) Developmental childhood

(20) Developmental childhood 
rituals are part of learning new skills, and accompanied by expres-sions of positive affect and interest. They are most intense in 4- to 8-year-olds, stress rules about daily life, help the child master anxiety, and enhance the socializing process. In contrast, persevera-tive behaviours in OCD are not goal-oriented, they are accompa-nied by a burdened, anxious affect, provoke frustration, are incapacitating and painful, and promote social isolation and regres-sive behaviour.
OCD must be distinguished from other anxiety disorders and, 
in some cases, from autism or schizophrenia. In phobias, subjects are preoccupied by their fears only when confronted to the phobo-gen stimuli, and, in separation anxiety disorder, fear of harm to

1683
parents or loved ones are part of persistent worries and behaviours 
which are not criticized by the child. Stereotyped movements and ritualistic behaviours are frequent in intellectual disability and autism, but they convey no particular intentionality, and the child does not try to resist them. In schizophrenia, there are erroneous belief systems in several areas, but the subject does not criticize them and does not consider the subsequent behaviours to be abnormal.
Tics should be differentiated from other types of abnormal

Tics should be differentiated from other types of abnormal 
movements which can occur in numerous congenital or acquired neurological and neuropsychiatric disorders (Sydenham’s chorea, encephalitis, Huntington disease, tuberous sclerosis, neuroacan-thocytosis, Wilson’s disease, head trauma, mental retardation, autism). The term of secondary tics or T ourettism has been applied to these disorders, and the abnormal movements can be chorei-form movements, dystonic movements, myoclonic movements, spasms, or stereotypies. Some medications such as central nervous system stimulants (methylphenidate, amphetamine, pemoline, cocaine), antihistaminic and anticholinergic drugs, antiepileptics (carbamazepine, phenytoin), antipsychotics, and opioids may also produce or exacerbate tics.
(21) The distinction between tic

(21) The distinction between tic 
disorders and other disorders with abnormal movements is based on anamnesis, family history, observation, and neurological exami-nation, which is usually normal in tic disorders. Speciﬁ  c diagnostic 
tests may be required to confirm neurological or exogenous causes.
Tics might be one of the most common behavioural problems in childhood, but estimates of the prevalence of tic disorders greatly vary because of differences in the methods used (e.g. parental report versus direct observation), differences in the populations surveyed (e.g. age and sex distribution), and the transient nature of tics. Surveys among school-age children indicate that up to 18 per cent of boys, and 11 per cent of girls manifest frequent ‘tics, twitches, mannerisms or habit spasms’ . Race and socio-economic status do not seem to inﬂ  uence the frequency of tics. There are

virtually no general population studies of transient tic disorder or chronic motor or vocal tic disorder. For T ourette’s disorder, most population-based surveys yield prevalence estimates in the range of 5–10 per 10,000, with children being more likely to be identiﬁ  ed 
than adults, and males more than females.
(22, 13)  In a study amongst 
all inductees into the Israeli Defence Force over 1 year, the point prevalence of T ourette’s disorder was 4.9 per 10 000 males and 3.1 per 10 000 females, and the prevalence of OCD was elevated in those with T ourette’s disorder (41.7 per cent vs. 3.4 per cent in others).
(23) One longitudinal study assessed the presence of tics 
and OCD in an epidemiological sample of individuals followed from childhood to adulthood.
(24) The prevalence of tics was

(24) The prevalence of tics was 
17.7 per cent at age 1–10 years, decreasing to 2–3 per cent in adoles-cence; childhood tics were associated with increased rates of OCD in adolescence; in adolescents with tics, the presence of comorbid OCD predicted persistence of tics into early adulthood.
There has been only one survey on the prevalence of OCD 
in children (5- to 15-year old), indicating an overall prevalence of OCD at 0.25 per cent, with an exponential increase as a function 
of age, from 0.026 per cent in 5–7 year olds to 0.63 per cent in 13–15 year olds.
(25) In adolescents, epidemiological studies using strict diagnostic criteria and structured clinical interviews have

(25) In adolescents, epidemiological studies using strict diagnostic criteria and structured clinical interviews have 
been conducted in several parts of the world, estimating the preva-lence of juvenile OCD between 1 and 4 per cent. In the largest study to date (N=5 596 high-school students), the lifetime prevalence of 
OCD in adolescents was estimated to 1.9 (±0.7) per cent, and none 
of the identiﬁ  ed cases had been previously diagnosed.
(8) In a later 
study,(26) the point prevalence of OCD was 3.6 (±0.7) per cent, 
decreasing to 1.8 per cent when excluding those individuals with only obsessions; among the OCD cases, there was a signiﬁ  cant 
elevation of tic disorders (T ourette’s disorder 5 per cent, chronic multiple tics 10 per cent, transient tics 10 per cent). In two longitu-dinal studies following cohorts of children in the community up to the age of 18 years, the prevalence for OCD ranged from 1.2 to 4 per cent.
(27, 28) Thus, it appears that OCD might be as frequent

(27, 28) Thus, it appears that OCD might be as frequent 
in adolescents as it is in adults (see Chapter 4.8).
Aetiology

Psychological theories of OCD have encompassed psychoanalytic as well as more general non-psychodynamic etiological approaches, focusing alternatively on volitional, intellectual, and/or emotional impairment. Freud’s famous patient, the Rat Man, has been seen as a paradigm of a psychologically determined illness, illustrating the central role of anal sadistic concerns with control, ambivalence, magical thinking, and the salience of defenses such as reaction formation, intellectualization, isolation, and undoing. Freud also provided fascinating speculations on the similarity between OC phenomena, children’s games, and religious rites. Later, Anna Freud stated that ‘obsessional outcomes are promoted by a constitutional increase in the intensity of the anal-sadistic tendencies probably as the result of inheritance combined with parental handling’ . However, despite the beautifully described dynamics of obsessional symptoms, most illustrative of unconscious processes, the psycho-analysts

result of inheritance combined with parental handling’ . However, despite the beautifully described dynamics of obsessional symptoms, most illustrative of unconscious processes, the psycho-analysts have also pointed out the extreme difﬁ  culty in treating

OCD with classical analytic treatment.
Even though psychological factors are insufficient to cause 
T ourette’s disorder, tic behaviours have long been identiﬁ  ed as 
stress-sensitive, and temporally associated with important events in the lives of children. In a prospective study over 2 years, children and adolescents with T ourette’s disorder and/or OCD experienced signiﬁ  cantly more psychosocial stressors than did healthy controls, 
and the level of psychosocial stress was a signiﬁ  cant predictor of 
future tic and OC symptoms severity.
(29)
Biochemical factors
Although a variety of biological aetiologies have been proposed in OCD since the 19
th century, modern neurobiological theories 
began with the clinical studies showing that clomipramine and other serotonin reuptake inhibitors ( SRIs ) had a unique efﬁ  cacy

began with the clinical studies showing that clomipramine and other serotonin reuptake inhibitors ( SRIs ) had a unique efﬁ  cacy 
in treating the disorder. This inspired a ‘serotoninergic hypothesis’ of OCD (see Chapter 4.8). In children, the involvement of the serotonin system in the pathophysiology of OCD is supported by one study in which improvement of OC symptoms during clomip-ramine treatment was closely correlated with pretreatment platelet serotonin concentration,
(30) and reports of decreased density of 
the platelet serotonin transporter in children and adolescents with OCD but not in those with T ourette’s disorder.
(31) However, the 9.2.8 obsessive–compulsive disorder and tics in children and adolescents

SECTION 9  child and adolescent psychiatry 1684
delayed and incomplete action of serotonergic drugs, suggesting 
multiple effects on other neurotransmitters as well, and numerous biochemical studies of OCD patients and controls have not yet indicated a single biochemical abnormality as a primary etiological mechanism in OCD.
In T ourette’s disorder, multiple neurochemical systems have 
been implicated by pharmacological and metabolic studies, but a primary disturbance in the dopaminergic system is supported by the tic suppressing effect of dopamine receptor antagonists (see below). Post-mortem studies have shown an increase in the num-ber of presynaptic dopamine transporter sites in the striatum and the frontal cortex of individuals with T ourette’s disorder. PET/SPECT studies have demonstrated greater binding to dopamine transporter sites in both the caudate and putamen nuclei,
(32)
increased dopamine release by psychostimulants in the putamen,(33)

(32)
and an association between density of dopamine receptors in the caudate and severity of tics.
(34) The ‘tonic-phasic hypothesis’ 
proposes both a hyperresponsive spike-dependent (phasic) dopami-nergic system (possibly related to an alteration in afferent cortical inputs), and a reduction in tonic dopamine levels (possibly second-ary to an overactive dopamine transporter system), that would upregulate pre- and postsynaptic dopamine receptors and further increase the phasic-tonic unbalance. There is also some evidence for the role of serotonin in tic disorders, notably a study showing that reduced serotonin transporter binding correlated with vocal tics and OC symptoms.
(35)
Genetic factors

(35)
In both OCD and T ourette’s disorder, twin and family studies provide strong evidence that genetic factors are involved in the ver-tical transmission of vulnerability within families. The average concordance rate in monozygotic twins is 65 per cent for OCD,
(36)
and 53 per cent for T ourette’s disorder.(37) Family studies have con-
sistently found higher rates of OCD and tic disorders in probands with paediatric OCD, as well as higher rates of tic disorders and OCD in those with tic disorders. Thus, Lenane et al.
(38) investigat-
ing 147 ﬁ  rst-degree relatives of children and adolescents with OCD 
found that 44 per cent of the families had a positive history of tics in at least one ﬁ  rst-, second-, or third-degree relative. Conversely, 
Pauls et al.
(39) reported that the prevalence rates of OCD and tic 
disorders were signiﬁ  cantly greater among the ﬁ  rst-degree relatives

disorders were signiﬁ  cantly greater among the ﬁ  rst-degree relatives 
of 100 probands with OCD (10.3 per cent and 4.6 per cent, respec-tively) than among relatives of psychiatrically unaffected subjects (1.9 per cent and 1.0 per cent). These ﬁ  ndings suggested that 
T ourette’s disorder and some forms of OCD could be variant expressions of the same underlying genetic factors.
Results from two genome-wide scans have been reported,
(40, 41)

(40, 41)
with the strongest linkage peaks being on chromosome 2 for T ourette’s disorder (p=0.00004), and chromosome 3 for OCD (p=0.0002); there were also regions that showed moderate evidence for linkage to both disorders. In early-onset OCD, family-based evidence for association at several serotonin system genes (SCL6A4, HTR1B, HTR2A) and brain-derived neurotropic factor (BDNF) has been reported in some studies, and the association seemed stronger in subjects with tic disorders associated with OCD.
(42)
There is also preliminary evidence for an association between OCD and two glutamate genes, the glutamate transporter gene (SLC1A1), and a glutamate receptor gene (GRIN2B).
(43) A complementary

(42)
(43) A complementary 
approach involving examining rare cases of cytogenetic abnor malitiesco-segregating with T ourette’s and related disorders has pointed to 
regions on chromosomes 3p, 7q, 8q, 9p, and 18q.(44)
Thus, as suggested by earlier family studies, OCD and T ourette’s 
disorder might have both shared and distinct susceptibility genes 
involved in their etiology. It is likely that epigenetic and non genet-ic factors may also contribute to phenotypal heterogeneity. A range of prenatal and perinatal events have been suggested as risk factors for increased tic severity, including lower birth weight, in utero exposure to caffeine, alcohol or tobacco, and maternal stress.
(45)

(45)
As the basal ganglia are especially sensitive to hypoxia, it is possible that factors associated with transient hypoxia could increase the risk for T ourette’s disorder in those with a genetic vulnerability.
Dysfunction of frontal–subcortical circuits
It has been known for a long time that OC symptoms could be associated with neurological disorders of motor control, including T ourette’s disorder, Huntington’s disease, Parkinson’s disease, as well as traumatic or infectious lesions of the basal ganglia.
(46)
Conversely, in both adults and children with typical OCD, an increased frequency of soft neurological signs has been reported.
(47)

(46)
(47)
Since the era of neuroimaging, numerous studies have consistently found that the ventral prefrontal cortical (VPFC) regions, such as orbital prefrontal cortex and anterior cingulate cortex, the striatum, the basal ganglia and the thalamus were basic brain structures involved in the pathophysiology of OCD. These studies have generally identiﬁ  ed abnormally high metabolic activity and/
or blood ﬂ  ow in the orbital cortex and the head of the striatal 
caudate nucleus in untreated OCD subjects at rest, compared to various control populations.
(48,49)  Furthermore, the same two

(48,49)  Furthermore, the same two 
regions, as well as the thalamus to which each projects, have shown further increase in activity during OC symptom provocation. In several functional neuroimaging studies of patients with child-hood onset OCD, measures of VPFC and striatal activity correlated positively with OCD symptom severity and treatment response.
(50,51)
Some studies have also indicated that the anatomy of the caudate, putamen and globus pallidus could differ between paediatric OCD patients and controls,
(52) especially in cases of paediatric autoim-
mune neuropsychiatric disorders associated with streptococcal infections (PANDAS).
(53) Although most studies have implicated

(53) Although most studies have implicated 
the VPFC in the pathogenesis of OCD, recent investigation sug-gests a role for the dorsolateral prefrontal cortex (DLPFC) as well. Thus, one study found a signiﬁ  cant increase in N-acetyl-aspartate 
(NAA), a neuronal marker of activity, in the left DLPFC of unmed-icated paediatric OCD patients compared to controls.
(54)
Recent MRI studies found that the volume of the caudate 
nucleus is decreased in both children and adults with T ourette’s disorder, whereas the volume of putamen and globus pallidus nuclei are primarily reduced in adults with the disorder.
(55) This is 
consistent with a study comparing monozygotic twins discordant for tic expression, in which caudate nuclei volumes were smaller in the more severely affected co-twin.
(56)In addition, subjects with

(56)In addition, subjects with 
T ourette’s disorder were found to have larger volumes in dorsal prefrontal and parieto-occipital regions.
(57) Although no associa-
tion was found between tic severity and the volumes of the basal ganglia, ratings of worst-ever tic severity were associated with larg-er orbito-frontal and parieto-occipital regions. In one recent study, cortical and subcortical hyperintensities that are considered as a subclinical manifestation of small-vessel disease, were signiﬁ  cantly 
more abundant in children and adolescents with T ourette’s

1685
disorder, OCD or ADHD than in healthy controls.(58) These results 
support a primary disturbance of the cortico-striato-pallidal-thalamo-cortical circuit, especially the projection into or out of the striatum. The small reduction of the caudate (about 5 per cent) may represent a marker for T ourette’s disorder, and larger prefron-tal cortex would likely result from the ability to suppress tics. Although tics are highly heritable, non genetic factors appear to contribute to these brain differences.
Autoimmune factors
For the last decade, clinical and research interest has grown in an autoimmune model of OCD and/or tic disorders, which could apply to a subgroup of subjects whose disorder begins abruptly during childhood. An association was ﬁ  rst reported between acute

onset OCD and Sydenham’s chorea, a childhood movement disor-der associated with rheumatic fever, which is thought to result from an antineuronal antibody-mediated response to group A beta-hae-molytic streptococcus (GABHS), directed at portions of the basal ganglia.
(59)OCD, or some of its symptoms, have been reported in 
70 per cent of Sydenham’s chorea cases.(60, 61)  Furthermore, in 
the absence of the neurological symptoms of Sydenham’s chorea, post-streptococcal cases of childhood-onset OCD, tics and/or other neuropsychiatric syndromes have been described under the acronym of paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Swedo et al.
(6)
deﬁ ned this novel group of patients using ﬁ  ve diagnostic criteria:

(6)
deﬁ ned this novel group of patients using ﬁ  ve diagnostic criteria: 
presence of OCD and/or tic disorder, prepubertal onset, episodic course of symptom severity, abrupt onset or dramatic exacerba-tions of symptoms temporally associated with GABHS infections (as evidenced by positive throat culture and/or elevated anti-GABHS titers), and association with neurological abnormalities (motoric hyperactivity or adventitious movements, such as chorei-form movements or tics). An antigen labelled D8/17, on the surface of peripheral blood mononuclear cells has been shown to be a marker for the genetic tendency to generate abnormal antibodies to GABHS. Two independent groups of researchers have found a greater expression of the D8/17 antigen in the B lymphocytes of patients with childhood-onset OCD or T ourette’s disorder 
compared with healthy controls, indicating that the presence 
of the D8/17 antigen may serve as a marker of susceptibility for OCD or tics.
(62, 63)

(62, 63)
Several follow-up studies of subjects treated for OCD during child-hood or adolescence have looked at the outcome of the disorder in early adulthood.
(11) All studies demonstrate the continuity of the 
diagnosis of OCD from childhood to adulthood: when subjects are still symptomatic, the main diagnosis is almost invariably OCD, although comorbid disorders are frequent, especially mood and/or anxiety disorders. Spontaneous course is most often marked by a waxing and waning severity of the disorder, whereas remissions under treatment can be followed by relapses, even after long periods of time. In the early studies in which subjects had received no or non-speciﬁ  c treatment, the recovery rate was poor (13–30 per cent). 
By the time patients had access to speciﬁ  c treatment with SRIs

By the time patients had access to speciﬁ  c treatment with SRIs 
and/or cognitive behavioural therapy (CBT), recovery rates increased to 55–65 per cent, although many of the symptom-free subjects at follow-up were still taking medication. A meta-analysis analyzed 16 studies that followed paediatric OCD patients between 
1 and 15 years.
(64) The overall remission rate (not fulﬁ  lling criteria 
for subthreshold or full OCD) was 40 per cent, with pooled mean persistence rates of 41 per cent for full OCD. Poor prognostic factors included a poor initial treatment response, and comorbid psychiatric illness.
In the majority of cases, tics are transient (present for less than

In the majority of cases, tics are transient (present for less than 
12 months), or wax and wane in severity with periods of exacerba-tion of an average duration of 9 weeks. The course of worst-ever tic severity usually falls between 7 and 14 years of age, which also includes the period when tics are most variable (10–12 years). By the end of the second decade, there is usually a steady decline in tic severity. However, adults who are able to suppress tics may be left with distracting urges, and a signiﬁ  cant minority (15–30 per cent) 
continues to have severe tics into adulthood.
(65) Despite substantial 
problems in childhood, the majority of patients with T ourette’s dis-order grow up to become well socially integrated and economically independent adults. However, as much as 25 per cent have persis-tent mental health problems. In those, tic severity ﬂ  uctuates, and

psychiatric co-morbidities (ADHD, other disruptive behaviour problems, OCD, mood and anxiety disorders, learning problems) are often the main determinants of global outcome. Poorer prog-noses are also associated with comorbid developmental disorders, chronic physical illness, unstable or unsupportive family environment, social difﬁ  culties, or exposure to psychoactive drugs 
such as cocaine.
(5)
Treatment
Evidence
The treatment of paediatric OCD has changed dramatically over the past 20 years, with two modalities being empirically shown to ameliorate the core symptoms of the disorder: CBT and pharma-cological treatment with SRIs. In T ourette’s disorder, D
2 dopamine 
antagonists have been used with relative success since the 1960s, and CBT techniques are being increasingly scrutinized.
Cognitive behavioural treatment

2 dopamine 
The cognitive behavioural model of OCD posits that compulsions function to reduce fear, and are subsequently reinforced by fear reduction, which prevents normal habituation and realistic appraisal of the threat value of feared stimuli. T echniques incorpo-rating exposure and ritual prevention are designed to break this cycle by exposing the individual to feared situations, while simulta-neously reducing compulsive behaviours.
(66) Discussion of 
obsessive thoughts, and other irrational beliefs, is often part of the exposure exercises but these informal cognitive techniques are used to support exposure rather than to replace it. The CBT of youth with OCD generally involves a three-stage approach, consisting of information gathering, therapist-assisted graded exposure with response prevention, and homework assignments.

(67) Anxiety 
management training plays an adjunctive role. For children with predominantly internalizing symptoms, treatment also includes relaxation and cognitive training. Families need to be involved, to varying extents according to individual situations. CBT is usually implemented with 13 to 20 weekly individual or family sessions, and homework assignments. Partial responders or nonresponders may require more frequent sessions, and out-of-ofﬁ  ce therapist-
assisted training.9.2.8 obsessive–compulsive disorder and tics in children and adolescents

SECTION 9  child and adolescent psychiatry 1686
A number of open trials, and four controlled studies (see 
Tables 9.2.8.1 and 9.2.8.2), have documented the beneﬁ  cial effects 
of CBT, alone or in combination with pharmacotherapy, for children and adolescents with OCD, with improvement measured on the CY-BOCS scores ranging from 25 per cent to 67 per cent. In the ﬁ  rst controlled study by Barrett et al. ,
(68) 88 per cent of youth treated with individual cognitive behavioural family treatment 
(CBFT), and 76 per cent of those treated with group CBFT showed clinically signiﬁ  cant improvement, as compared to no improve-
ment for any patients in the waitlist condition. Treatment gains were maintained at 12- to 18-month follow-up, with a total of 70 per cent of participants in individual therapy, and 84 per cent in Table 9.2.8.1  Controlled studies of pharmacological or psychological treatment in paediatric OCD

Study, Year N (age), Study duration Drug (daily dose), Study design Outcome % Improvement from baseline on active 
treatment for OC symptoms
Flament et al., 1985 19 (6–18 yr), 5 wk CMI (mean 141 mg)
Crossover vs. PBOCMI > PBO at 3–5 wk22–44 %
Leonard et al. , 1989 47 (7–19 yr), 5 wk CMI (mean 150 mg)
Crossover vs. DESCMI > DES at 3–5 wk 19–44 %
DeVeaugh-Geiss et al. , 
199260 (10–17 yr), 8 wk CMI (75–200 mg)
Parallel vs. PBOCMI > PBO at 3–8 wk 34–37 %
Riddle et al. , 1992 14 (8–15 yr), 8 wk FLX (20 mg)
Crossover vs. PBOFLX > PBO at 8 wk 33–44 %
March et al. , 1998 187 (6–17 yr), 12 wk SER (mean 167 mg)
Parallel vs. PBOSER > PBO at 3–12 wk 21–28 %
Riddle et al. , 2001 120 (8–17 yr), 10 wk FLV (50–200 mg)
Parallel vs. PBOFLV > PBO at 1–10 wk 21–25 %
Geller et al. , 2001 103 (7–17 yr), 13 wk FLX (mean 40 mg)
Paralell vs. PBOFLX > PBO at 7–13 wk 25–49 %
Liebowitz et al. , 2002 43 (8–17 yr), 16 wk FLX (mean 64 mg)
Parallel vs. PBOFLX > PBO at 16 wk 42 %

Geller et al. , 2004 203 (7–17 yr), 10 wk PAR (mean 30 mg)
Parallel vs. PBOPAR > PBO at 2–10 wk 47–65 %
Barrett et al. , 2004; 2005 77 (7–17 yr), 14 wk Randomized parallel study ICBFT 
vs. GCBFT vs. control conditionICBFT and GCBFT > control 
condition at 14 wk65 % for ICBFT
60 % for GCBFT
CMI: clomipramine; DES: desipramine; FLV: ﬂ  uvoxamine; FLX: ﬂ  uoxetine; PAR: paroxetine; PBO: placebo; SER: sertraline
ICBT: individual cognitive behavioural treatment, GCBT: group cognitive behavioural treatment
Table 9.2.8.2  Comparative studies of cognitive behavioural treatment and pharmacological treatment in paediatric OCD
Study, Year N (age), Study duration Drug (daily dose), Study design Outcome % Improvement / Remission for OC 
symptoms
De Haan et al., 1998 22 (8–18yr), 12 wk CMI CMI (25–200 mg) vs. BT BT > CMI Improvement from baseline

symptoms
BT: 59.9 %
CMI: 33.4 %
POTS Team 2004 112 (7–17yr), 12 wk SER (mean 150 mg) vs. PBO vs. CBT 
vs. Combi (CBT+SER) 3-site study, Parallel designCombi > CBT = SER > PBO 
effect size: 1.4 (Combi), 0.97 (CBT), 0.67 (SER)Improvement from baseline Combi: 
53 %; CBT: 46 %;
SER: 30 %; Placebo: 15 %
Remission post-treatment
(CY-BOCS<10)Combi: 53.6 %; CBT: 39.3 %
SER: 21.4 %; PBO: 3.6 %
Asbahr et al.,  2005 40 (9–17 yr), 12 wk 
F/U: 9 moSER (mean 137 mg) vs. GCBT Signiﬁ  cant improvement on 
CY-BOCS with both GCBT and SER
Relapse during F/y: 50% (SER), 
5 % (GCBT)NR
BT: behavioural treatment; CBT: cognitive behavioural treatment; CMI: clomipramine; Combi: combination treatment; F/U: follow-u p; GCBT: group cognitive behavioural treatment; NR: not 
reported; PBO: placebo; POTS: paediatric obsessive–compulsive disorder treatment study; SER: sertraline

1687
group therapy diagnosis-free at follow-up, and no signiﬁ  cant 
difference between the two treatment modalities.(69) More evidence 
for the efﬁ  cacy of CBT in the treatment of paediatric OCD comes 
from three studies that have compared CBT to pharmacotherapy and/or their combination (see below).
Behavioural techniques play an important role in the treatment 
of tics, although generally as adjunctive to medication. In a model of operant conditioning, ticking relieves unpleasant premonitory sensations, which reinforces the maintenance of tics. Habit reversal (HR) is based on awareness training regarding the premonitory urges, followed by training a competing response (a movement that involves the same muscle group as the tic) after the ﬁ  rst sensa-

tion that a tic is about to occur. The response must be temporally contingent on each occurrence of the urge, but using a muscle group related or unrelated to the tic may not be crucial for tic suppression. Relaxation, self-monitoring, contingency training for positive reinforcement of not ticking, and social support are used as ancillary components of HR. An extension of HR is exposure and response prevention (ERP): after the urge, the patient suppresses the tic voluntarily, which should lead to its extinction. Both techniques have been showed to yield relatively large effect size (1.06 to 1.42) in reducing tic severity at post-treatment
(70)
and long-term follow-up.(71) A recent review of the literature(72)
concluded that the use of HR to treat tics can currently be classiﬁ  ed 
as a ‘well established’ treatment, and that of ERP as a ‘probably efﬁ cacious’ treatment. Contrary to initial fears, these behavioural

as a ‘well established’ treatment, and that of ERP as a ‘probably efﬁ cacious’ treatment. Contrary to initial fears, these behavioural 
techniques have no negative consequences, such as substitution of the targeted tics, or post-suppression rebound or worsening due to increased awareness of premonitory urges.
In the past 25 years, a number of randomized, controlled clinical trials (summarized in Table 9.2.8.1) have been conducted in chil-dren and adolescents with OCD demonstrating, as in adults, the selective and unique efﬁ  cacy of the SRIs in the short-term and 
long-term treatment of the disorder.
(67, 73–79) Results have consis-

tently shown that: the antiobsessional action of the SRIs is inde-pendent of the presence of depressive symptoms at baseline; their antiobsessional action takes longer to appear than their antidepres-sant action; the therapeutic response occurs gradually over a few weeks to a few months; ﬁ  nal response is most often partial, with a 
mean reduction of OC symptoms from baseline to post-treatment ranging from 19 per cent to 44 per cent across measures and across studies.
(80) Geller et al.(81) conducted a meta-analysis of 12 ran-
domized, controlled medication trials in children and adolescents with OCD (total N=1 044), demonstrating that all serotonergic medications were highly signiﬁ  cantly superior to placebo, with 
consistent ﬁ  ndings across studies but a modest overall effect (the

consistent ﬁ  ndings across studies but a modest overall effect (the 
pooled standard mean difference between active drug and placebo was only 0.46). Clomipramine was statistically superior to the spe-ciﬁ c serotonin reuptake inhibitors (SSRI), but temporal trends 
might, at least, partly explain this apparent superiority: the clomip-ramine trials were conducted earlier in time when no other treatment was available, while the patient population included in subsequent controlled trials have changed over the years with increased availability of pharmacological alternatives. No head-to-head paediatric studies of clomipramine versus an SSRI have been conducted. The recommended daily dosages for SSRIs in the treat-ment of paediatric OCD are shown on Table 9.2.8.3.A few studies, summarized in Table 9.2.8.2, have compared 
pharmacological treatment to CBT or their combination for children and adolescents with OCD.
(82–84)  In the U.S. 12-week

(82–84)  In the U.S. 12-week 
paediatric OCD treatment study (POTS; N=112), the combined treatment with CBT and sertraline had the best rate of clinical remission (53.6 per cent vs 39.3 per cent on CBT alone, 21.4 per cent on sertraline alone, and 3.6 per cent on placebo); the remission rate for the combined treatment was not statistically different from that in the CBT only condition.
(83) In Asbahr et al.(84) study, both group 
CBT and sertraline induced a signiﬁ  cant improvement in OC 
symptoms, but after a 9-month post-treatment follow-up period, subjects in the group CBT condition had a signiﬁ  cantly lower rate 
of symptom relapse. A few case reports have also indicated that the addition of CBT to pharmacotherapy can allow successful with-drawal from medication.
The use of clomipramine can entail anticholinergic side effects

The use of clomipramine can entail anticholinergic side effects 
(dry mouth, dizziness, headache, tremor, fatigue, constipation, sweating, dyspepsia, sexual dysfunction), which may not abate over time and even increase with ascending titration.
(85) Clomipramine 
can cause tachycardia and prolongation of the QT and QTc inter-vals, and ECG monitoring is recommended.
(86) Risks of toxicity 
also include seizures, and rare cases of sudden death have been reported in children taking tricyclic antidepressants.
(87) Although 
less frequent and less disturbing that the secondary effects of clomipramine, the most commonly described adverse effects of the SSRIs include gastro-intestinal (nausea, constipation, abdominal pain), and central nervous system complaints (headache, tremor, drowsiness, akathisia, insomnia, disinhibition, agitation).
(88) The

(88) The 
possible induction of mania can also be of concern. Although not commonly reported in clinical trials, the eventual occurrence of sexual side effects should be reviewed with adolescents, since these may impact adherence to treatment. Recent reports of possi-ble growth suppression associated with the SSRIs suggest that monitoring of height may also be advisable.
(89) A recent concern, 
highly visible in the media, has been a possibly increased risk for suicidal thoughts, self-harm and/or harm to others, in youth treated with the SSRIs. However, no individual OCD study has documented a signiﬁ  cantly increased risk for suicidal ideation or behaviour on Table 9.2.8.3  Recommended daily dosages of serotonin reuptake 
inhibitors for the treatment of paediatric OCD
Medication Starting DoseaInitial Targeted Doseb,cMaximal Doseb
Citalopram 10 mg 40 mg 60 mg

Escitalopram 5 mg 20 mg 20 mgFluoxetine 10 mg 40 mg 80 mgFluvoxamine 25 mg 200 mg 300 mgParoxetine 10 mg 40 mg 60 mgSertraline 25 mg 100 mg 200 mgClomipramine 10 mg 150 mg 250 mg
a these doses should be given for about one week, that is about the time necessary to 
achieve steady state for these drugs, with the exception of ﬂ  uoxetine. This would ensure that no agitation or increased anxiety is triggered by the medication.
b for subjects weighing at least 50 kg; for smaller individuals, a weight-proportional regimen 
should be used
c according to side effects and response9.2.8 obsessive–compulsive disorder and tics in children and adolescents

SECTION 9  child and adolescent psychiatry 1688
a SSRI compared to placebo. In pooled analyses of the controlled 
studies conducted in youth with OCD and other anxiety disorders, behavioural side effects variously labelled as activation, akathisia, disinhibition, impulsivity, and hyperactivity have appeared, but there was no evidence for a signiﬁ  cant increase in the relative 
risk of suicidal thoughts or behaviours.
(90) In a recent review of 
27 trials of antidepressants in participants younger than 19 years (including six trials for treatment of OCD), there was an increased risk difference of suicidal ideation/suicide attempts across trials and across indications for drug versus placebo, but no completed suicide, and the beneﬁ  ts of antidepressants appeared much greater 
than the risk.
(91)In any case, rigorous clinical monitoring for 
suicidal ideation and other potential indicators for suicidal behav-iour remains advised in youth treated with the SSRIs.

The mainstay of treatment for T ourette’s disorder has been tradi-
tional antipsychotics, i.e. the potent dopamine (D2) postsynaptic blockers haloperidol and pimozide.
(92)The usual starting dose is 
0.25 mg/day of haloperidol or 1 mg/day of pimozide. Increments (0.5 mg haloperidol or 1 mg pimozide) may be added at 7 to 14 days intervals, up to 1–4 mg/day for haloperidol and 2–8 mg/day for pimozide. Atypical antipsychotics have also been used for the treatment of tics, and differences in efﬁ  cacy appear to be related 
to their relative potency of dopamine blockade. Risperidone has been shown to be superior to placebo,
(93, 94) and equally effective 
to pimozide,(95, 96)  at doses ranging from 1 to 3 mg/day (starting 
dose, 0.25–0.50 mg). The speciﬁ  c D2 receptor-blocking agents,

dose, 0.25–0.50 mg). The speciﬁ  c D2 receptor-blocking agents, 
tiapride and sulpiride, have been commonly used for the treatment of tics in Europe in doses ranging from 15–500 mg/day and 200–1 000 mg/day, respectively, but they are not available in the U.S. The use of traditional antipsychotics is limited by a range of side effects, both in the short term (parkinsonism, dystonia, dyskinesia, and akathisia) and in the long term (tardive dyskinesia). The newer antipsychotics appear to have a lower frequency of neurological side effects in the short term, and a lower relative risk of tardive dyskinesia, but weight gain, hyperlipidemia and diabetes are of growing concern. Among the antipsychotics used in the treatment of tics, pimozide is the most likely to be associated with prolonged QTc interval, although this is a rare occurrence at therapeutic doses. An ECG is recommended before starting treatment, during

the dose-adjustment phase, and annually during ongoing treat-
ment. Patients should also be informed that the risk for cardiac conduction abnormalities may increase when pimozide is com-bined with drugs that inhibit cytochrome P450 3A4 isoenzyme (e.g. macrolide antibiotics, SSRIs, etc.).
(97)
Clonidine is an antihypertensive agent ( α-2-adrenergic agonist) 
that has been shown effective for treatment of tic disorders, pre-sumably via acute and chronic downstream effects on dopamine. Clinical trials indicate an average 25–35 per cent reduction in symptoms over 8 to 12 weeks. Clonidine seems especially useful in improving attention problems and ameliorating complex motor tics. Treatment must be started at a low dose (0.05 mg in the morning), and slowly increased to 0.15–0.30 mg per day, given in several doses throughout the day. The major side effects are seda-tion, hypotension, dizziness, and a decrease of salivatory ﬂ  ow;

blood pressure and pulse should be measured at baseline and mon-itored during dose adjustment, and patients and families should be educated about the potential for rebound increases in blood pres-sure, tics, and anxiety upon abrupt discontinuation.
(98) Guanfacine 
is another α-adrenergic antihypertensive that has entered into  clinical practice. Given the added disability attributable to ADHD 
in children and adolescents with tic disorders, a treatment combin-ing an α-2 agonist and a stimulant may produce better outcomes 
than either alone. Recent studies suggest that the acute onset or worsening of tic symptoms among patients receiving stimulants may be simply an expression of the spontaneous time course of tics and comorbid ADHD.
(99) Atomoxetine is a selective norepinephrine 
reuptake inhibitor that reduces signiﬁ  cantly ADHD symptoms, 
and may also improve tics.

As described above, OCD and tic disorders are frequently chronic, and most treatments, notably medication, are suspensive but not curative. Therefore, when deﬁ  ning a treatment plan, clinicians 
should be aware that they embark on a long-lasting task.
CBT is generally favoured as the initial treatment of choice for 
OCD, especially in milder cases without signiﬁ  cant comorbidity, 
whereas presence of comorbid depression, anxiety, disruptive behaviour, or insufﬁ  cient cognitive or emotional ability to cooperate 
in CBT, are indications for including an SRI in the initial treatment. However, youth who have OCD and comorbid conditions may not be as responsive to SSRIs for OCD, as shown in Geller et al.
(100) study,

(100) study, 
in which the response rate was 75 per cent in the non-comorbid OCD group, but signiﬁ  cantly lower when OCD was comorbid with 
ADHD (56 per cent), tic disorder (53 per cent), or oppositional deﬁ ant disorder (39 per cent); comorbid OCD may also be more 
vulnerable to relapse with SSRI discontinuation. Although the SSRIs are indicated for OCD, depression, and anxiety disorders, which make them an ideal ﬁ  rst drug teatment when OCD is 
comorbid with an affective disorder, monitoring for the emergence of manic symptoms is required. The treatment of OCD comorbid with ADHD using stimulants may present a challenge because the-oretical concerns exist that stimulants may increase obsessional symptoms. However, it is common clinical practice to combine a SSRI (or CMI) with a psychostimulant.
(101)
Similar to adult patients, at least one third of young people with 
OCD prove refractory to treatment, and many ‘responders’ exhibit only partial response.

(101)
(11)For children and adolescents who do not 
seem to beneﬁ  t from SRI treatment, the ﬁ  rst steps are (i) to reeval-
uate the diagnosis and associated features, and (ii) to review the adequacy of the dose, duration, and compliance with medication. Then, for many youth with a partial response to pharmacotherapy, further improvement may be obtained by adding a concurrent CBT intervention. Furthermore, if a ﬁ  rst SSRI trial fails to produce an 
adequate response, pharmacological algorithms generally recom-mend switching to a second SSRI. Considering that these drugs all inhibit the 5-HT transporter, the ﬁ  rst drug can be discontinued 
abruptly, and the second initiated at a dose in the middle of its therapeutic range. Because of its longer half-life, if ﬂ  uoxetine has

abruptly, and the second initiated at a dose in the middle of its therapeutic range. Because of its longer half-life, if ﬂ  uoxetine has 
been the ﬁ  rst treatment, it could be stopped abruptly, but the sec-
ond SSRI must be titrated slowly. If two or three successive trials of SSRIs have failed, clomipramine is generally considered as the next 
option. Given that it has a half-life in the same range as most of the 
other SRIs, no time should be wasted in the substitution, unless a switch from ﬂ  uoxetine is carried out.
Very few drug augmentation or combination strategies have been 
tested for youth with treatment-resistant OCD. The addition of risperidone to various SRI agents (clomipramine, sertraline, ﬂ  uox-
etine, paroxetine) has been reported in a series of OCD adolescents

1689
with no comorbid tic disorder, with only modest beneﬁ  ts.(102)The
combination of an SSRI with clomipramine takes advantage of the pharmacokinetic and pharmacodynamic interactions of these medications, but it is important to monitor for adverse effects, particularly cardiovascular side effects, and the possible emergence of a serotonin toxic syndrome. Combining two SSRIs is a common clinical practice, despite the risk for drug interaction, since all SSRIs inhibit cytochrome P-450, and combinations may result in increased blood levels of each SSRI.
If short-term treatment with a SSRI often leaves OCD youth 
with residual symptoms, over an extended period of SSRI treat-ment, they may experience greater improvement. Three long-term (1–2 years) open studies have documented continued improve-ment after the acute phase, but at a much slower rate, with ﬂ  uvox-

amine, sertraline, and citalopram. Similarly, in two continuation studies of clomipramine (4–12 months), treatment continued to be effective and well tolerated. There are hardly any data on the doses of SRIs that should be used in treatment prolongation, versus those used in the acute treatment phase. It would thus be prudent to maintain the regimen that produced the maximal improvement in the acute treatment. The most recent guidelines for adult patients recommend a minimum treatment of one to two years, followed by a gradual taper to, ﬁ  rst, avoid discontinuation phenomena and, 
second, monitor patients for a possible deterioration.
(103)In youth, 
it is particularly recommended to choose a period free of stress (e.g. summer vacation) for tapering medication, and to provide alternative psychological support (CBT, education on relapse risk and management) for the period of discontinuation.
Although tics are a common childhood problem, only a small

Although tics are a common childhood problem, only a small 
minority of cases ﬁ  nd their way to clinics. Given the waxing and 
waning nature of tic disorders, usual therapeutic practice will ini-tially focus on careful clinical observation, along with educational and supportive interventions, and pharmacological treatments are held in reserve. The decision about whether and how to treat will depend on the primary diagnosis, and the degree of interference with the child’s development and functioning. Most simple tics occurring in the absence of severe functioning impairment respond 
to a simple explanation of the mechanisms. In case of comorbidity 
with a mood and anxiety disorder, it is not uncommon to see improvement in tic severity after successful treatment of the affective disorder with a SSRI.
(104) When tics are responsible of 
functional impairment, the decision to use medication follows careful assessment and identiﬁ  cation of target symptoms, that are

functional impairment, the decision to use medication follows careful assessment and identiﬁ  cation of target symptoms, that are 
interfering in the patient’s quality of life. The selection of medica-tion is based on a balance of risks and beneﬁ  ts, and in order not to 
expose the subject to excessive unwanted side effects, pharmaco-logical treatment should not aim at complete disappearance of tics. For tics of moderate severity, clonidine or guanfacine may be considered as the ﬁ  rst line treatment given their safety margin, and 
an expected 30 per cent decrease in tic severity may be sufﬁ  cient. 
For tics in the marked or severe range, however, more potent medications, such as antipsychotics, that decrease tics severity by 35–60 per cent should be considered, despite the increased risk of adverse effects. In addition, patients with tic disorders and their 
families should be cautioned about both licit and illicit drug use,

families should be cautioned about both licit and illicit drug use, 
since sympathomimetic agents ranging from decongestants through speed and cocaine, markedly exacerbate tics.
For children and adolescents with OCD and comorbid tic disor-
der, the SSRIs alone might have little anti-obsessional effect, and there are reports suggesting that ﬂ  uvoxamine and ﬂ  uoxetine may 
exacerbate or even induce tics in some patients. The adult litera-ture, and a few case reports of children and youth with OCD and comorbid tic disorder suggest that combined treatment with a SRI and a low dose of risperidone or another atypical antipsychotic is a reasonable option.
(105) Using data from the POTS study, March 
et al.(106) found that tic disorders appeared to adversely impact the 
outcome of medication management of paediatric OCD, in contrast to CBT outcomes which were not differentially impacted.
Therapeutically, the ﬁ  nding of possible autoimmune cases of

Therapeutically, the ﬁ  nding of possible autoimmune cases of 
OCD and tic disorders raises the clinical possibility that immuno-suppressant treatments might be effective, and a few experimental studies have been conducted. A double-blind, placebo-controlled study in resistant cases of PANDAS supported the efﬁ  cacy of both 
plasma exchange and intravenous immunoglobulin compared to a sham condition at one month, and the effects were maintained after 1 year for 82 per cent of subjects with follow-up assessment.
(107)
In another study antibiotic prophylaxis with penicillin or azithro-micin was administered for 12 months to a group of children with PANDAS; compared to the year prior to entry in the study, signiﬁ  cant decreases were observed in the number of streptococcal 
infections, and the number of neuropsychiatric exacerbations with both prophylactic treatments.

(108) There is preliminary evidence for 
the efﬁ  cacy of CBT in OCD cases of the PANDAS phenotype.(109)
However, it is still unknown what percentage of children with OCD 
may be part of the PANDAS subgroup, and neither immunosup-pressant nor antibiotic treatments are to be used for such cases out of the context of board-approved research protocols. Nevertheless, children with abrupt onset or exacerbation of OC and/or tic symp-toms require careful consideration of medical illnesses including upper respiratory tract infections during the preceding months, to be promptly treated if present. A throat culture and antistreptoly-sin O or antistreptococcal DNAase B titers may be considered to assist in diagnosing a GABHS infection.
(101)
Even if they are less efﬁ  cacious alone, other treatment modalities

(101)
Even if they are less efﬁ  cacious alone, other treatment modalities 
should not be neglected. The effectiveness of psychotherapy per se—apart from behavioural and cognitive interventions—on OCD and tic disorders has not been demonstrated, but the symptoms may have a profound impact on the life of subjects affected, and traditional psychotherapeutic approaches may be useful to help children and adolescents address the intrapsychic conﬂ  icts that 
may affect or result from their illness. Some families become exten-sively involved in participating in compulsive rituals or reassuring obsessional worries, others become mired in gruelling angry strug-gles with their symptomatic child. Work with families on how to manage the child’s symptoms, cope with the stress and family disruption that often accompanies OCD and tic disorders, and participate effectively in behavioural or pharmacological treatment is crucial. Most cognitive behavioural approaches of paediatric

OCD include the involvement of a parent in some therapeutic 
sessions, and it is noteworthy that the Barrett et al.
(68) study, 
which actively involves the family in the child’s treatment, reports improvement in the highest range of outcomes among CBT studies. In children with tic disorders, oppositional, deﬁ  ant, and 
disruptive behaviours are common, and parenting skill training may be an important adjunctive to treatment. For cases of very incapacitating OCD, there is some empirical evidence that milieu therapy in an inpatient setting may be a useful resource. Finally, the growing availability, in many countries, of family support and 9.2.8 obsessive–compulsive disorder and tics in children and adolescents

SECTION 9  child and adolescent psychiatry 1690
advocacy groups for patients with OCD and tic disorders may be 
most useful to alleviate the discouragement and incomprehension created by these disorders, and give access to appropriate treatment resources.

At present, there is no known preventive strategy individually targeted at either OCD or tic disorders. However, early interven-tion and comprehensive treatment, as long as needed, is certainly the best way to prevent severe incapacitation, and achieve complete recovery in some cases. Even when response to successive treatment efforts is less than optimal, the improvement in function and qual-ity of life may be considerable. In families with one or several cases of OCD or tic disorders, clinicians should be attentive to the onset of similar symptoms in children and siblings, and treat cases of newly occurring disorder early and vigorously. Although this might concern only a fraction of patients, evidence of the onset or exacerbation of OCD or tics associated with streptococcal exposure warrants standard antibiotic treatment and ongoing monitoring for recurrent infection.

Paediatric OCD is the disorder, in child psychiatry, whose clinical picture most closely resembles its adult counterpart. Despite a relative diversity, the symptom pool is remarkably ﬁ  nite, and very 
similar to that seen in older individuals. Prevalence, comorbidity, and response to behavioural and drug treatment also appear simi-lar across the lifespan. For tic disorders, there is continuity between child and adult presentations, but the disease is much more prone to resolve spontaneously, or to be less disruptive in adulthood. Both OCD and tics occur more often in males than in females, and are likely to be linked to an array of neurobiological abnormalities, many of which remain to be understood.
Invaluable beneﬁ  ts can now be obtained from available behav-
ioural and pharmacological treatments, but complete remission remains uncertain and long-term management may be required. 
Thus, the treatment of OCD and tics in children and adolescents

Thus, the treatment of OCD and tics in children and adolescents 
remains a clinical challenge. It requires careful assessment of the targeted symptoms and, in many cases, comorbidity; attention to the quality of the child’s functioning at home and with peers; use of speciﬁ  c CBT interventions, which are not readily available (or 
accessible) in all communities; patience and caution in the choice and adjustment of medication; and vigilance in watching potential side effects. Given the possible chronicity of OCD and/or tic disorders, and their changing patterns in severity and impact over the childhood and adolescent years, optimal treatment generally requires a long-term ongoing relationship with the child and family.
Current conceptualizations of OCD and tic disorders have been

Current conceptualizations of OCD and tic disorders have been 
shaped by advances in systems neuroscience and functional in vivo neuroimaging. Continued success in these areas should lead to the targetting of speciﬁ  c brain circuits for more intensive research. This 
should include testing novel pharmacological agents, tracking treatment response using neuroimaging techniques, and possibly investigating circuit-based therapies using deep-brain stimulation for refractory cases. The identiﬁ  cation of the PANDAS subgroup of 
patients, with an abrupt onset and dramatic exacerbations, certainly brings new insights into the pathophysiology of OCD and tic dis-
orders, and may lead to new assessment and treatment strategies. The increasing evidence for susceptibility genes in OCD and tic disorders will also doubtless point to new therapeutic directions. Furthermore, it is likely that many of the empirical ﬁ  ndings used

in research on paediatric OCD and tic disorders will be relevant to a better understanding of both normal development, and other disorders of childhood onset.
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in pediatric patients treated with antidepressant drugs. Archives of 
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45(10), 1171–8.
9.2.9 Sleep disorders in 
children and adolescents
It was argued in Chapter 4.14.1 that sleep disorders medicine should

It was argued in Chapter 4.14.1 that sleep disorders medicine should 
be viewed as an integral part of psychiatry, whatever the age group of patients, because of the various close connections between sleep disturbance and psychological disorders seen in clinical practice. This is certainly the case regarding child and adolescent psychiatry in view of the high rates of psychiatric disorder of which sleep disturbance is often a part, and also the frequent occurrence of sleep disorders in young people with potentially serious developmental effects of a psychological and sometimes physical nature. The temp-tation to view children’s sleep disorders as merely transitory problems, mainly in infancy, encountered by many parents and of no lasting or serious signiﬁ  cance, should be resisted. This may be 
true for some families but is frequently not the case in others.

The following account summarizes sleep disorders in childhood 
and adolescence. Familiarity is assumed with the earlier accounts of 
sleep disorders in adults (4.14.1), including the introduction to that sec-tion which covers basic aspects of sleep and other fundamental issues.
Sleep and sleep disorders in children 
compared to adults
In spite of the fact that much has now been discovered about the 
special characteristics of sleep disorders occurring at an early age, very little of this information has found its way into the training of paediatricians, child and adolescent psychiatrists, psychologists, or other professionals involved in the care of children. This must mean that many treatment and preventive possibilities are missed.
The solution does not lie simply in extending the practice of

The solution does not lie simply in extending the practice of 
adult sleep disorders medicine to children. Children are not minia-ture adults and they need special approaches reﬂ  ecting their many 
differences from older patients. These differences extend from basic features of sleep to various aspects of sleep disorders.
Sleep physiology
Profound changes take place during childhood in basic sleep physi-ology although many are complete by about 6–12 months of age. In general, there is a progression towards differentiation and orga-nization of conventionally deﬁ  ned sleep states, shorter sleep time, 
less napping, less slow wave sleep ( SWS ), and longer sleep cycles.
Speciﬁ  c aspects of particular clinical importance are as follows:
◆ Typical sleep duration (including naps) at different ages as shown 
in Table 9.2.9.1.9.2.9 sleep disorders in children and adolescents

SECTION 9  child and adolescent psychiatry 1694
◆ The body clock controlling (amongst other processes) the 
circadian sleep–wake cycle has become established by about 6 months.
◆ Rapid eye movement ( REM ) sleep is prominent in early infancy, 
perhaps reﬂ  ecting its role in brain maturation and early learning, 
and possibly explaining why sleep is fragile at this stage.
◆ In comparison, by early childhood SWS  is especially pronounced. 
This predisposes children of that age to arousal disorders (e.g. sleepwalking) which arise from SWS .
◆ Between about 5 years and puberty, overnight sleep is especially 
sound and alertness is maximal during the day. Various condi-tions causing excessive daytime sleepiness in adults (e.g. narco-lepsy) may not have this effect in children because of this increased alertness. However, overnight sleep may become extended.
◆ In contrast, adolescence is characterized by an increase in day-time sleepiness. The amount of SWS  decreases, the sleep phase is

◆ In contrast, adolescence is characterized by an increase in day-time sleepiness. The amount of SWS  decreases, the sleep phase is 
physiologically delayed and, with the onset of puberty, there is no longer the decrease in physiological sleep requirements seen progressively at earlier ages. The combination of these factors and strong inﬂ  uences to stay up late (especially at weekends 
but perhaps also during the week) for social and recreational purposes frequently causes unsatisfactory sleep–wake patterns.
Parental inﬂ  uences
The inﬂ  uence of parents is seen throughout children’s sleep disor-
ders medicine.
◆ Especially in the case of young children, parents’ perceptions usually determine whether there is a sleep problem. The same sleep pattern or behaviour may be a problem to one family but not another. Factors inﬂ  uencing parental attitudes include their

expectations, family and cultural practices (e.g. regarding par-ents and children sleeping together), and their own emotional state. Sometimes parents can be reassured that what they think is a serious problem about their child’s sleep is, in fact, within the normal range. The view taken of the situation might be the result of parental psychiatric illness needing attention in its own right; children of mothers with an affective illness have been shown to have an increased rate and severity of sleep problems although the nature of the connection is debatable.
◆ Conversely, parents may not seek help for their child’s sleep when they ought to do. They may be unaware of the problem, indiffer-ent, or they may mistakenly believe that the child’s sleep problem is inevitable and untreatable. This mistaken view is sometimes expressed by parents of children with a learning disability 
(intellectual disability) whose sleep problems can be particularly 
severe yet amenable to treatment.

◆ Parental practices are commonly the reason why a child’s sleep problem develops or is maintained. Early child-rearing practices determine sleep–wake patterns which can be delayed or disrupted by over-conscientious night-time feeding in infancy, failure to set limits on bedtime activities, or inconsistency (see later). Sleep disorders of physical origin may be complicated in these ways and exacerbated. It follows that treatment of many sleep disor-ders relies heavily on correcting parenting practices.
◆ Sometimes parents are not motivated to improve their child’s sleep for reasons that may be difﬁ  cult to inﬂ  uence. For example, 
a child’s presence in the parental bed may be welcome by one partner as a means of distancing himself or herself from the other at night. Families of handicapped children may lose their extra state ﬁ  nancial allowance if their child’s sleep problems are

successfully treated.
◆ The child’s basic attitude to sleeping is also inﬂ  uenced by its 
parents. Wider cultural factors are important but, within west-ernized societies, the child’s attitudes to going to sleep and being separated from its parents at night are strongly inﬂ  uenced by 
their ability to settle the child without being anxious about the separation. Children depend on their parents to provide positive attitudes to sleeping and to avoid negative associations such as disputes, punishment, and rejection.

◆ Especially in the early years, most children need their parents’ help in coping with night-time separation from them, and the potentially frightening experience of the dark or their own thoughts and fantasies. Infants need the comfort of physical contact. T oddlers are helped by bedtime routines and comforting ‘transitional objects’ , and encouragement to become ‘self-soothing’ so that they can fall asleep without their parents’ presence and attention (see later). Parents’ ability to provide such help depends on their personality and sensitivity and mental state and perhaps their cognitions about their child’s sleep based partly on their own experiences in childhood. Hopefully, older children and adolescents become increasingly independent.
Effects on parenting and the family
The effects of a child’s persistent sleep disturbance on family life, including its possible inﬂ  uence on parenting skills, is another 
important dimension.

◆ Mothers of children with a learning disability and severe sleep problems are reported to be more irritable, concerned about their own health, and less affectionate towards their children, with less control and increased use of punishment compared with mothers of such children without sleep problems. Similarly, associations have also been suggested between sleeplessness in toddlers in the general population and family problems, includ-ing marital discord and possibly physical abuse of the child.
◆ Family tensions are likely to increase when diagnosis of the child’s sleep disorder is delayed or inaccurate, or when effective treatment is not provided.

◆ Some reports have suggested that successful treatment of the child’s sleep problems generally leads to improvement in the Table 9.2.9.1  Average sleep requirements at different ages
Term birth 17 h
1 year 14 h2 years 13 h4 years 12 h10 years 10 hAdolescence 9 h plus*
*Many adolescents are thought to obtain far less sleep than this.

1695
mother’s mental state, conﬁ  dence in her own parenting ability, 
her relationship with the child, and also the child’s behaviour. Wider aspects of family function, including effects on siblings, have received little attention.
Developmental effects of sleep disturbance
◆ These parental and wider family issues indicate ways in which a child’s psychological and social development can be affected by persistent sleep disturbance. In addition, children can be dis-tressed by their experience of sleep disorder phenomena. Examples include night-time fears (which may be intense) alarming hypnagogic imagery, or sleepwalking and sleep (night) terrors which can be embarrassing, especially if they occur away from home. Excessive daytime sleepiness often leads to educa-tional problems and can produce extreme reactions such as the denial, aggression or depression described in narcolepsy, or accidents and substance abuse in adolescence.

◆ In addition to these largely indirect ways in which a child’s sleep disorder may have psychological effects, sleep disturbance can produce direct effects on mood, behaviour, and cognitive function. The developmental consequences might become severe if not arrested at an early age.
◆ Adolescents appear to be at particular risk of sleep loss and its possible psychological consequences, i.e. depressed mood, anxiety, behaviour problems, alcohol abuse, and even attempted suicide, as well as lower academic performance. The causal relationship between sleep loss and these problems, however, have yet to be fully established. The same is true of the outcome of attempts to correct this sleep loss by various means.
◆ Even impairment of physical growth is associated with sleep dis-turbance. Failure to thrive is a recognized possible consequence of early onset obstructive sleep apnoea ( OSA ) and possibly other

◆ Even impairment of physical growth is associated with sleep dis-turbance. Failure to thrive is a recognized possible consequence of early onset obstructive sleep apnoea ( OSA ) and possibly other 
severe and persistent sleep disturbance, perhaps as a result of reduced slow wave sleep ( SWS ) with which the production of 
growth hormone is closely linked.
◆ Other possible physical consequences of sleep disruption includes impaired immunity and endocrine disorders.
Patterns of occurrence of sleep disorders
◆ Some sleep behaviours which are developmentally usual in children are abnormal in adults and require investigation. Examples are bedwetting and repeated napping. Certain sleep disorders are seen exclusively in children (e.g. sleeplessness caused by infantile colic). Others, such as settling problems and confusion arousals, occur primarily in children (see later).

◆ Sleeplessness caused mainly by child-rearing practices is particu-larly common in early childhood. That attributable to the delayed sleep phase syndrome (see later) is considered to be particularly common in adolescence.
◆ Many of the parasomnias (such as headbanging, sleepwalking, or sleep terrors) are more common in childhood where, generally, they represent a temporary developmental phase without patho-logical signiﬁ  cance. The same behaviours in adults might be 
more likely to be manifestations of psychological problems requiring exploration.◆ Some sleep disorders thought to be conﬁ  ned to adulthood are 
now recognized in children. While much attention has been paid to OSA in adults, it is now thought that at least 2 per cent of chil-dren have this condition to some degree. Restless leg syndrome (RLS) and periodic limb movements in sleep ( PLMS ) are now

known to occur not uncommonly in children. The RLS may explain some cases of ‘growing pains’ . PLMS has been implicated as a cause of poor quality sleep resulting (as in other forms of sleep disturbance) with daytime attention deﬁ  cit hyperactivity 
disorder ( ADHD ) type of symptoms. Narcolepsy starts by the 
age of 15 years in at least one-third of cases. Even REM sleep behaviour disorder (once thought to be conﬁ  ned to elderly 
males), or something similar, has been reported in children and adolescents.
Manifestations of sleep disorders

◆ The clinical features of basically the same sleep disorder can be very different in children compared with older people. The over-all behavioural effects of excessive sleepiness in adults are a reduction of physical and mental activity. In contrast, its effects in young children can be increased activity with irritability, tantrums, or other behavioural difficulties. Some examples of ADHD are thought to be the result of sleep disorders (OSA, PLMS, or circadian sleep–wake rhythm disorder) with improve-ment in the difﬁ  cult behaviour following treatment of the sleep 
disorder.

disorder.
◆ OSA illustrates the important differences between children and adults, not only in the clinical manifestations of a particular sleep disorder but also in the underlying cause and treatment needs. Similarly the many manifestations of narcolepsy in childhood may be very far removed from the classical narcolepsy syndrome in adults, at least in its fully developed form. The same sleep dis-order may also show different physiological features according to age. Diagnostic criteria (e.g. for OSA and narcolepsy) derived from polysomnographic (PSG) studies in adults do not necessar-ily apply in children and may well need modiﬁ  cation.
Misinterpretation of children’s sleep disorders
Chapter 4.14.1 contains an account of the fundamental issue that, 
especially if clinicians are unfamiliar with the manifestations and consequences of the many sleep disorders now documented in the 
second edition of the International Classiﬁ  cation of Sleep Disorders

second edition of the International Classiﬁ  cation of Sleep Disorders 
(ICSD-2), there is a serious risk that these disorders will be mis-construed as something else (or even overlooked completely). The examples given include a number of particular relevance to practice in child psychiatry and paediatrics.
(1)
Treatment and prognosis
◆ Because of the aetiological differences discussed earlier, especially parental involvement, treatment often needs to be very different in children compared to adults. Appropriate behavioural approaches usually entail alterations to parenting practices designed to be acceptable and feasible in each individual family. Other forms of treatment, including chronobiological measures (such as adjustment of sleep schedules from the delayed sleep phase syndrome in adolescence) usually require considerable parental involvement. The same is true of the general sleep 9.2.9 sleep disorders in children and adolescents

SECTION 9  child and adolescent psychiatry 1696
hygiene principles described in Chapter 4.14.2. Explanation and 
(where appropriate) reassurance for the child and parents is an essential part of any treatment and may be effective in their own right without the need for more speciﬁ  c measures. As in adults, 
medication has a limited part to play overall.
◆ An optimistic point of view can be taken of the treatment of most children’s sleep disorders because children’s sleep is usually more amenable to change than that of adults where the factors underlying the sleep problem may well have become well estab-lished and complicated, as in many cases of chronic insomnia. However, treatment needs to be chosen carefully and imple-mented properly, and parents’ conﬁ  dence in the recommended

measures, and their willingness and ability to play their part in treatment, are an important determinant of success or failure. In some instances, it is not possible to implement a treatment programme for the child until parents themselves have been helped (e.g. by treatment for a depressive illness) or problems in the family as a whole have been resolved.
The various means by which sleep disorders might generally be detected and assessed are described in Chapter 4.14.1. These sub-jective and objective approaches need to be modiﬁ  ed for use with 
children because of the involvement of parents, developmental factors, and the differences between children and adults regarding clinical manifestations and diagnostic criteria.
The detection of sleep problems can be improved by routinely 
asking basic screening questions as part of the history-taking in any child:
◆ Does the child have difﬁ  culty getting to sleep or staying asleep?

◆ Is there excessive sleepiness during the day?
◆ Are there episodes of abnormal behaviour or experiences at night?
Positive answers to any of these questions call for a detailed sleep 
history.
Sleep history and general review
This is the cornerstone of sleep assessment. Unfortunately, history- taking schedules are usually perfunctory in the attention they pay to sleep and its possible disorders. Parents and also the child (if old enough) should be interviewed and the reasons for any disparities con-sidered. Sometimes sibs or teachers can provide important additional information. The main aspects that should be covered are as follows:
◆ Current sleep problems and their evolution.
◆ Past treatments and their effects.
◆ Review of the child’s current 24 h sleep–wake cycle(see Table 9.2.9.2) in order to determine in particular

(a) duration of sleep(b) quality of sleep (continuous or disrupted)
(c) timing of sleep
(d)  features suggestive of speciﬁ  c sleep disorders (e.g. breathing 
difﬁ culty or jerking limbs).
◆ Sleep environment and arrangements.
◆ Development of the child’s sleep patterns and problems.◆ General review of possible sleep symptoms.
◆ Family history of sleep disorder or other conditions.
Asleep questionnaire  completed by parents before the interview 
can provide a useful outline account of these and other aspects.(2)
Additional parts of the overall review of children with a sleep 
problem that are important in order to identify possible contribu-tory factors are as follows:
◆ Developmental history including developmental delays, illnesses, or signiﬁ  cant events at school or within the family.

◆ Review of physical health.
◆ Physical examination.
◆ Assessment of behaviour and emotional state.
◆ Family history and circumstances.
Following the initial consultation, a sleep diary , kept over a 
period of 2 or more weeks, can be particularly useful. This provides a more complete and balanced view than that obtained especially from fraught parents likely to give a distorted or unbalanced retro-spective account.
Special investigations (see also Chapter 4.14.1)
These depend on the nature of the sleep problem:
◆ Indications for PSG are essentially the same as for adults.Table 9.2.9.2  Review of child’s 24 h sleep–wake pattern (modiﬁ  ed 
according to child’s age)
Evening
Time of evening meal
Other evening activities
Going to bed
Preparation for bed, by whom
Time of going to bedReluctance to go at required time, parents’ reactions

Evening
Fears, ritualsWanting to sleep with someone, other comfortsTime taken to fall asleep, other experiences during that period
When asleep
Wakings, frequency, causes ability to return to sleep
Episodic events, exact nature, timing, frequency
Other behaviours during sleep, e.g. snoring, restlessness, bedwettingParents’ reaction to night-time events
Waking
Wakes spontaneously or needs to be woken up
Time of ﬁ  nal waking
Total duration of sleep periodLongest period of uninterrupted sleep
On waking: preoccupations, mood, feeling of being refreshed, other 
 experiencesDifﬁ  culty getting out of bed, time of getting out of bed
Daytime
Sleepiness, naps
Lethargy
Mood
Concentration and performance
Other unusual episodes

1697
◆ The use in children of multiple sleep latency tests ( MSL T ) as an 
objective measure of sleepiness is hampered by the absence of good normative data at different ages. However, in school-aged children, about 16–18 min to fall asleep is considered normal; less than this might indicate signiﬁ  cant daytime sleepiness which 
is also indicated by falling asleep in three or more of the naps. Nevertheless, in the presence of sleep disorders usually charac-terized by excessive sleepiness, MSLT results can be normal in late childhood because of the naturally enhanced daytime wakefulness at that age.
◆ Actigraphy , which provides information unobtrusively on basic 
sleep–wake patterns, is well established for children of all ages.
◆ Other possible measures  include toxic screening and the special 
tests mentioned earlier in Chapter 4.14.1.
Children at special risk of sleep disturbance

The prevalence of children’s sleep disorders is not known with any accuracy, even for those which are severe and persistent. A number of methodological problems make it difﬁ  cult to collect accurate 
ﬁ gures and no really vigorous attempt has yet been made to over-
come them. It seems that 20–30 per cent of children from infancy to adolescence have sleep problems that are considered signiﬁ  cant 
by them or their parents.
The occurrence of sleep problems exceeds this overall rate con-

siderably in various categories within the general population as a whole, and also in certain clinical subgroups. Determining the exact nature and cause of the sleep problems in these high risk groups (and also in any other affected children), with a view to successful treatment, is important because of the possible adverse effects on the child in a family that have just been discussed. 
Behavioural sleep problems probably predominate throughout 
these high risk groups but sleep disorders of a different nature may well be encountered instead or as well as those of behavioural origin.
Children in the general population
◆ Reference was made earlier to the fact that children in general appear to be particularly prone to different types of sleep disor-ders at certain ages of development i.e. early infancy, early child-hood, and adolescence.

◆ Adverse psycho-social circumstances are also associated with increased risk of childhood sleep problems. The importance of such factors as the degree of organization in family life, parental concern, child-rearing practices, and the mental health of parents was stressed earlier. High rates of various sleep problems, 
as well as other psychological difﬁ  culties, have been reported in 
homeless children.
Children with psychiatric disorders
High rates of sleep disturbance have been described in child psychiatric groups in general compared with other children, and in 
speciﬁ  c psychiatric disorders.
◆ Various sleep problems, including panic attacks, have been 
described in anxious children  in general including those with 
panic disorders . Similarly, many types of sleep problem (includ ing 
nightmares and other disturbed nocturnal episodes, excessive daytime sleepiness, and bedwetting) have been reported to be 
particularly frequent in traumatized children  including those

particularly frequent in traumatized children  including those 
who have suffered burn injury, abuse, or road trafﬁ  c accidents. 
Treatment of the sleep disturbance has appeared to improve their emotional state but further research is needed to asses the thera-peutic contribution of speciﬁ  c treatment for the sleep disorder as 
part of the overall care of the traumatized children.
◆ Difﬁ culty in sleeping is the main complaint in children and in 
adolescents with severe depressive disorders  but many complain 
of excessive sleepiness, possibly because of difﬁ  culty getting to 
sleep and/or poor quality sleep.
◆ Parental reports of sleep problems in children with ADHD

are very common. Parental impressions can be distorted but preliminary objective evidence also suggests that persistent sleep disturbance is common and sometimes important as the primary cause (or a signiﬁ  cant contributory factor) rather than 
simply a consequence of ADHD. It was mentioned earlier that ADHD symptoms have sometimes been attributed to deﬁ  nitive 
sleep disorders in which sleep quality is impaired, with improve-ment in ADHD symptoms following treatment of the sleep dis-order. Preliminary studies of sleep physiology or other objective aspects of sleep in children have also produced evidence of sleep abnormalities. Even where ADHD is attributable to other factors, sleep disruption is likely to worsen a child’s behaviour, meriting treatment in its own right wherever possible.

◆ Other psychiatric disorders  in which different types of sleep 
 disturbance is reported to be prominent are autism (including  circadian sleep–wake rhythm disorders and Asperger’s syndrome, tic disorders including T ourette syndrome (sleeplessness and para-somnias), and obsessive–compulsive disorders (poor quality sleep).
 Sleep complaints are also prominent in the chronic fatigue syn-
drome. As mentioned earlier, disruption by frequent awakenings (not obviously attributable to daytime inactivity) has been described in teenagers with this condition suggesting that day-time symptoms might be at least partly attributable to poor quality sleep. Occasionally Munchausen’s syndrome by proxy have come to light in the form of parental complaints of a sleep disturbance. Reports of the sleep of conduct disordered children are in keeping with the expectation that their sleep is disturbed because of their adverse or disorganized home and social cir-cumstances, and general way of life.

◆ Apart from psychiatric disorders themselves, medications  used 
in their treatment may affect sleep. Stimulant medication for ADHD appears to cause sleeping difﬁ  culties in some children 
but some children with ADHD may settle to sleep more readily even if their medication is given later in the day because this improves their bedtime behaviour. See Chapter 4.14.1 for other possible medication effects on sleep.
Children with a learning disability or other 
neurological disorder
Particularly high rates of sleep disturbance has been consistently 
reported in children with a learning disability . The disturbance is 
often severe, poorly managed and, therefore, persistent.
◆ Sleep problems in this group are often behavioural in origin (largely attributed to parenting practices), arising from often 9.2.9 sleep disorders in children and adolescents

SECTION 9  child and adolescent psychiatry 1698
understandable over-permissiveness, inconsistency, or parents’ 
inability to set limits on their child’s behaviour because of their own emotional state or excessive demands on their time. Other physical sleep problems include some chronic physical conditions. OSA features prominently in various speciﬁ  c learning difﬁ  culty 
conditions such as Down syndrome, the mucopolysaccharidosis and fragile X syndrome. Epilepsy can also play an important role as well as other co-morbid conditions.
◆ Sleep problems are also widely reported in children with neuro-
degenerative disorders , e.g. Rett’s syndrome and other neuro-
logical disorders such as head injury. Again, behavioural factors might be partly the reason, although interference with sleep mechanisms also seems likely, at least in the advanced stages of the disease.
Children with other chronic physical illness

Acute physical illnesses disturb sleep but only for the duration of the illness in most cases. By comparison, chronic illnesses are commonly complicated by long-standing sleep disturbance caused in various ways (see Chapter 4.14.1 for medical causes of sleep disorder some of which apply to paediatric cases).
Main sleep problems: sleeplessness
The second edition of the International Classiﬁ  cation of Sleep 
Disorders was outlined in Chapter 4.14.1. The following selective account of sleep disorders in children and adolescents is organized according to the three main types of sleep complaint: sleeplessness, excessive sleepiness, and the parasomnias. Childhood psychiatric and medical conditions in which sleep disturbance is a prominent feature has already been mentioned. Emphasis is placed on the differential diagnosis of sleep complaints and also on points of particular relevance to psychiatric practice.

The breakdown of problems and disorders according to age 
should not be interpreted too strictly as there is overlap between the different age groups. In addition to speciﬁ  c treatments men-
tioned for particular sleep disorders, the promotion of adequate sleep, regular sleep habits, and the other sleep hygiene principles 
referred to in Chapter 4.14.1 are important. Evidence for the effec-
tiveness of psychological treatments for sleeplessness in children is reviewed in detail elsewhere.
(3)
Infants

(3)
Infants
Ways of preventing or dealing with babies’ sleep problems are rarely taught to parents or prospective parents, with the result that many suffer needless sleep loss and distress because the child does not sleep well. It is important to encourage good sleep habits from the start to avoid bad sleep habits later on. There are certain gen-eral guidelines for achieving this, admitting that babies vary tem-peramentally in their response to recommendations and parents vary in their ability to adhere to them. The main basic principles are as follows:
◆ Establishing a consistent 24 h routine, including a bedtime routine that provides cues that is timed to go to sleep.

◆ Not prolonging night-time feeding beyond the age (about 6 months) when the baby’s body clock has developed enough to conﬁ  ne feeding to daytime.◆ T eaching the baby to fall asleep alone so that when he or she 
wakes in the night (a natural occurrence at all ages) it will be possible to fall asleep again without requiring parental attention (‘self-soothing ’).
◆ Establishing a clear difference in the infant’s experience between 
day and night to help to develop his/her body clock which controls sleep and wakefulness.
◆ Ensuring the environment is conducive to sleep.
Safety measures to reduce the risk of the infant coming to harm 
at night from suffocation, or other breathing problems associated with sudden infant death syndrome ( SIDS ), should also be part 
of parent education about sleep.
(4) Main recommendations are:

(4) Main recommendations are: 
having the infant sleep on his/her back and on a ﬁ  rm mattress that 
will not obstruct breathing, ensuring that his or her face cannot be covered during the night, ensuring the bedroom is smoke free, and avoiding co-sleeping if either parent has consumed alcohol or has taken medication or other substances with a sedative affect. Also, the baby should not be overheated at night.
Toddlers and pre-school children
About 30 per cent of children of this age present a problem of recurrently not going to bed at the required time, and/or waking repeatedly at night and demanding their parents’ attention includ-ing coming into their bed. Medical factors must be excluded but the usual explanations are behavioural especially:
◆ Anxiety about separating from parents at night

◆ Unhelpful associations with going to bed, e.g. stimulating activi ties
within the bedroom, threats, or recriminations
◆ Inadequate limit setting on bedtime or night-time behaviour
◆ Failure to require self-soothing ways of coping with night waking.
Behavioural methods of treating these problems can be very 
effective, even in severe and long-standing cases, including children with developmental disorders such as learning disability or autism, providing the treatment programme is implemented properly. The main methods used include graded changes and desensitization rather than leaving the child to cry (a quickly effective measure but one which is unacceptable to many parents).
School-age children
Some of the causes of sleeplessness in pre-school children still apply in older children but other factors become more relevant with increasing age:
◆ Night-time fears  are common from very early childhood

◆ Night-time fears  are common from very early childhood 
onwards although, in keeping with cognitive development, the content of the fears changes from aspects of the immediate envi-ronment (e.g. shadows or noises) through imaginary objects (ghosts, monsters) or the dark, to more realistic and speciﬁ  c fears 
concerning the child’s own health. Such fears are usually tran-sient and require only reassurance and comfort until they cease.
 In some children the fears are so intense and persistent that they 
reach phobic proportions and need special attention. The cause of the fear should be investigated. The night-time fear might be one aspect of an anxiety state, including post-traumatic stress dis-order in which case the child might also suffer from nightmares.

1699
The content of the fear or nightmare might be revealing, suggest-
ing abuse, for example. Other sleep disturbances (e.g. alarming hypnagogic hallucinations) may be the cause of the night-time fears. The child’s reluctance to go to bed because he or she is gen-uinely afraid must be distinguished from pretending to be afraid as a delaying tactic.
 Behavioural treatment is said to be very effective in cases of 
severe night-time fears. The child with night-time fears should be helped by positive associations with bedtime and by not going to bed so early that he or she lies awake in a fearful state.
◆ Even without night-time fears, a child will be unable to settle to sleep if bedtime is too early . Like some adults and even

◆ Even without night-time fears, a child will be unable to settle to sleep if bedtime is too early . Like some adults and even 
other species, children often have an evening period of intense wakefulness and activity before they begin to relax in preparation for sleep. A child is physiologically unable to sleep if put to bed in this ‘forbidden zone’ . Instead the sequence of events leading up to bedtime should be arranged so that the child goes to bed when ‘sleepy tired’ .
◆ W orry and anxiety  about daytime matters such as school prog-
ress may cause difﬁ  culty in getting to sleep or staying asleep. The 
original source of concern may no longer exist but the difﬁ  culty

original source of concern may no longer exist but the difﬁ  culty 
falling asleep may persist because the child has developed the habit of lying awake in bed in an agitated state (‘conditioned insomnia’). Sympathetic discussion of the child’s worries, atten-tion to the source of concern if possible, and ways of helping the child to relax at night, are generally thought to help. More speciﬁ  c psychiatric measures will be needed if the child has an 
anxiety or depressive disorder, or if there is evidence of serious problems within the family.
◆ ‘Childhood onset insomnia ’ or ‘idiopathic insomnia’  refers to a 
lifelong difﬁ  culty sleeping not attributable to environmental, 
emotional, or medical factors and therefore of constitutional origin. The condition is usually diagnosed retrospectively in adult life.
◆ Early morning waking  (i.e. when a child habitually wakes very

◆ Early morning waking  (i.e. when a child habitually wakes very 
early, does not return to sleep, and is noisy or demands atten-tion) can be very distressing to parents, and disruptive to the whole family. In pre-school children, early waking may be the result of excessive or otherwise inappropriate napping, but at a later age the problem may be part of the advanced sleep phase syndrome. In this disorder the child’s bedtime and sleep onset is so early that his or her sleep requirements have been met well before other members of the family wake in the morning. Gradual resetting of the child’s sleep onset time is required.
 In older children and adolescents early morning wakening may 
be part of an anxiety or depressive disorder. Otherwise, the child may have been woken too early by noise or other environmental factors which intrude into his or her sleep.
Adolescents
High rates of insomnia have been consistently reported in adolesce nts.

High rates of insomnia have been consistently reported in adolesce nts. 
The change from the highly efﬁ  cient sleep of pre-pubertal children 
to less satisfactory sleep in adolescence was mentioned earlier, including the biological inﬂ  uences in this change. The psychologi-
cal and social demands and stresses of adolescence further conspire 
to disrupt sleep patterns. Worries, anxiety, and depression are commonly quoted reasons for not being able to sleep at this age. 
Nicotine, alcohol, and caffeine-containing drinks, as well as illicit drug use, are additional possible inﬂ  uences.
Difﬁ culty getting off to sleep is often part of the delayed sleep

Difﬁ culty getting off to sleep is often part of the delayed sleep 
phase syndrome which is reported to be particularly common in adolescence. In this condition (which will be considered further in relation to excessive sleepiness as this is often the major complaint) there is a physiological inability to go to sleep until much later than the required time because of a shift in the sleep phase. The adoles-cent’s reluctance to go to bed earlier (or the bedtime struggles of parents with younger children with this disorder) are often misin-terpreted as ‘difﬁ  cult’ behaviour. Instead of recriminations and 
attempts to set limits, the timing of the sleep phase needs to be reset by so-called chronotherapeutic means.
Main sleep problems: excessive 
daytime sleepiness
Despite the evidence that it is a common problem,(5) sleepiness

Despite the evidence that it is a common problem,(5) sleepiness 
remains neglected in child and adolescent psychiatry and in paediatrics:
◆ Part of the explanation is that sleepiness is not usually viewed as a medical problem by parents, teachers, and children themselves, the symptoms being misperceived as laziness or disinterest. Otherwise, they may be interpreted as depression or even limited intelligence.
◆ Another difﬁ  culty is that excessive sleepiness can take various 
forms including prolonged overnight sleep or inappropriate periods of sleep during the day.
◆ Extreme degrees of sleepiness will cause a reduction of activity at any age, but lesser degrees in children may produce irritability, over-activity, restlessness, poor concentration, impulsiveness, or aggression. Explanations of such behaviours other than sleep loss or disturbance (such as ADHD) are more likely to be considered, as mentioned earlier.

◆ A high level of daytime alertness in older pre-pubertal children may be sufﬁ  cient to offset a tendency to sleep, providing a differ-
ent clinical picture of sleepiness but not seen at a younger or older age.
Because of these problems of recognition, the prevalence of 
excessive sleep in children and adolescents is not known. Clearly, it is not rare in view of the range of underlying conditions causing it, many of which are individually quite common.
It is important to establish that the problem really is excessive 
sleepiness. ‘Tiredness’ is an ambiguous term: ideally, sleepiness should be distinguished from fatigue or lethargy, without necessar-ily the need to sleep, for which different explanations are likely including physical illnesses, such as anaemia or endocrine disorders in which other signs are usually present. Occasionally, excessive sleepiness with long periods in bed or at home is simu-lated in order to escape from a difﬁ  cult situation. Detection of such

cases requires very careful clinical evaluation and assessment and possibly PSG.
Excessive sleepiness is mainly a problem in older children and (espe-
cially) adolescents. Many teenagers complain about excessive sleepi-ness but it has been claimed that very many more than those who seek help are likely to be suffering from chronic sleep deprivation 9.2.9 sleep disorders in children and adolescents

SECTION 9  child and adolescent psychiatry 1700
or  ‘sleep debt ’ . As mentioned earlier, the adverse effects of this are 
thought to be wide-ranging from underperformance at school, col-lege or work, to road trafﬁ  c accidents and other mishaps, as well as 
antisocial behaviour.
(6) Sometimes the situation is complicated by 
the use of stimulants to stay awake, and alcohol or sedative drugs to 
get to sleep.
The differential diagnosis of excessive sleepiness can be consid-
ered in terms of three main categories of cause: insufﬁ  cient sleep, 
disturbed sleep, and an increased need for sleep (Table 9.2.9.3).
Insufﬁ  cient sleep
The combination of late-night social activities or staying up late for 
study, and having to get up early for school or college reduces the number of hours many adolescents sleep to below that needed for satisfactory daytime functioning. Difﬁ  culty getting off to sleep at

night and recurrent waking makes the problem worse (or may be sufﬁ cient in themselves to reduce or seriously impair sleep). The 
result is considerable difﬁ  culty getting up in the morning, irritabil-
ity, emotional liability, lethargy, tiredness, or actually falling asleep during the day.
Correction of the problem of late-night social activities requires 
a change of lifestyle or other measures which may be difﬁ  cult to 
achieve without there being strong motivation to do so. The ideal solution is an agreed, co-operative effort on the part of both the young person and parents.
More speciﬁ  c measures will be needed if the habit of going 
to bed late has developed into a disturbance of the circadian sleep–wake cycle. This may take the form of irregular sleep–wake schedules or, more usually, the delayed sleep phase syndrome 
(DSPS)  which deserves special mention because it is common, 
especially in adolescents, and potentially very disruptive.

The time at which children fall asleep may become delayed during 
a period of illness, or because of protracted bedtime disputes about going to bed. In adolescents the problem arises from habitually staying up late for social or other reasons, especially at weekends or during holidays. After a time (the length of which varies with the individual) the sleep phase becomes physiologically delayed with 
the result that it becomes impossible to go to sleep earlier by choice, in spite of feeling tired and having been awake for a long time. Entreaties to go to bed at a sensible time and get up on time for school are likely to be ineffective.
The diagnostic features of DSPS are persistently severe difﬁ  culty 
getting to sleep, uninterrupted sound sleep, great difﬁ  culty getting

getting to sleep, uninterrupted sound sleep, great difﬁ  culty getting 
up for school or work, and sleepiness and under-functioning especially during the ﬁ  rst part of the day, giving way to alertness 
in the evening and early hours. The abnormal sleep pattern is maintained by sleeping in very late when able to do so at weekends 
and during holidays.
Treatment consists of gradually and consistently changing the 
sleep phase to an appropriate time. This can be achieved by slowly advancing the sleep phase (e.g. by 15 min a day) where the phased delay is about 3 h or less. More severe forms of the disorder require progressive sleep phase delay in 3 h steps (‘round the clock’). Additional measures to maintain the improved sleep schedule include early morning exposure to bright light and ﬁ  rm agreement

with the adolescent to maintain the new pattern of social activities and sleep. The place of melatonin remains unclear in view of the many uncertainties about its use and potential hazards, including possible adverse affects on reproductive physiology.
Achieving and maintaining an improved sleep–wake schedule by 
these means may not be easy. The difﬁ  culties are compounded if 
there is a vested interest in maintaining the abnormal sleep pattern, for example to avoid school (‘ motivated sleep phase delay ’). The 
presence of psychological problems, including depression, may well make successful treatment less likely. ‘Conditioned insomnia’ may appear similar to DSPS but its origins and treatment are different.
Disturbed nocturnal sleep

Daytime sleepiness, despite apparent normal time asleep at night, suggests that the restorative quality of sleep is impaired. Poor quality sleep can result from frequent awakenings or less obvious arousals including brief subclinical interruptions (or ‘fragmentation’) of sleep. Sleep may be disturbed by the following:
◆ Excessive caffeine, alcohol, or nicotine (combinations are partic-ularly hazardous), and illicit drug use and withdrawal.
◆ Medical and psychiatric disorders in childhood, and some of their treatments.
◆ Other sleep disorders: frequent parasomnias are likely to be obvious but periodic limb movements in sleep (now considered to be more important in childhood than previously thought) are much more subtle in their effects on sleep continuity.

◆ Sleep-related respiratory problems, including OSA. This condi-tion merits some emphasis because of its widespread occurrence: at least 2 per cent of children in the general population are affected with a peak onset at 2 to 6 years. The prevalence is much higher than this in various learning disability syndromes such as Down syndrome, as mentioned earlier.
There are important differences between OSA in children and 
OSA in adults. The typical adult with OSA is an obese middle-aged male who snores very loudly, under-functions during the day and usually responds to continuous positive airway pressure (CPAP) treatment at night.Table 9.2.9.3  Differential diagnosis of excessive sleepiness in older 
Late-night activities combined with getting up early
Insomnia
Erratic sleep–wake patternsDelayed sleep-phase syndrome
Disturbed sleep at night
Sleep-related upper airway obstructionRecreational drugs (caffeine, alcohol, nicotine)

Insomnia
Illicit drugs (including withdrawal)
Medical and psychiatric disordersOther sleep disorders (frequent parasomnias, periodic limb movements in sleep)
Increased need for sleep
Narcolepsy
Idiopathic central nervous system hypersomniaDepression
Neurological diseaseKleine–Levin syndrome (intermittent sleepiness)Menstruation-related hypersomnia (intermittent sleepiness)

1701
◆ In contrast, most children with OSA are not obese, the usual 
causes are large tonsils and adenoids (the removal of which can be beneﬁ  cial), the sex ratio is equal and, whereas adults have pro-
longed obstructive apnoeas, children often have partial airway obstruction with hypoventilation, actual apnoea events being less frequent and shorter. As already mentioned, the result may be over-activity and other disruptive behaviour rather than obvious sleepiness during the day.
Clinical assessment is the cornerstone of recognizing OSA.
◆ Night-time signs suggesting the diagnosis are combinations 
of snoring (although only about one in ﬁ  ve children who snore 
most nights have this condition), other noises suggesting breath-ing difﬁ  culties during sleep, paradoxical chest–abdomen respira-

tory movements, unusual sleeping positions including neck extension, very restless sleep, profuse sweating, nocturnal enure-sis, and sudden distressing awakenings during the obstructive event. There is also a higher incidence of other parasomnias but for reasons that are unclear.
◆ Daytime features include mouth breathing and adenoidal facies, headache and bad mood on wakening, and the behaviour problems already mentioned.
◆ Physical examination may reveal the anatomical cause of the obstruction (usually enlarged tonsils and adenoids). Radiological studies are required in the more complicated cases. PSG with respiratory measures is needed to assess the severity of the obstruction and the effects on blood gases during sleep which may be greater than suspected from clinical ﬁ  ndings.

Treatment is essential to counter or prevent physical and psycho-
logical complications. This usually consists of adenotonsillectomy or, much less commonly, other measures such as CPAP depending on the individual case.
Disorders involving an increased tendency to sleep
This occurs where prolonged or otherwise excessive sleep is an intrinsic part of the condition, rather than a consequence.
Narcolepsy is a neurological disorder mainly affecting REM sleep physiology. It is not the rarity once supposed; prevalence in the United States has been estimated at 4–9 per 10 000.
Onset has occurred by adolescence in a high number of cases but

Onset has occurred by adolescence in a high number of cases but 
the diagnosis is often not made for several years. The reasons for this are that symptoms may be subtle in their early stages, concealed, misinterpreted as laziness or psychological disorder such as depres-sion or conversion disorder, or overshadowed by the child’s extreme emotional reaction to the condition. Especially because of its many manifestations in childhood, narcolepsy is a good illustration of how a sleep disorder can be misconstrued as another type of clini-cal condition, especially when familiarity with the ﬁ  eld of children’s 
sleep disorders is limited.
(7)
The clinical presentation of early narcolepsy is very variable 
and some time usually elapses before the classic combination of daytime sleep attacks, overnight sleep disruption, cataplexy, hypna-gogic hallucinations, and sleep paralysis develop if, indeed, it does at all. In young patients the ﬁ  rst sign may consist of no more than

prolonged overnight sleep.
It is appropriate to consider narcolepsy in any young person 
who is excessively sleepy during the day without an obvious explanation, but repeated clinical and PSG assessment may be 
required at intervals before a deﬁ  nite diagnosis can be made, 
including its distinction from other forms of sleepiness such as the group of conditions known as idiopathic CNS hypersomnia . The 
demonstration of low CSF levels of the neuropeptide hypocretin (orexin) is now considered diagnostic of narcolepsy. The PSG features of narcolepsy in adults, which are described elsewhere (Chapter 4.14.3) do not necessarily apply in the childhood stage of the condition.
Narcolepsy is a persistent and disturbing condition for which 
careful treatment with medication together with ancillary meas-ures, as well as much support and advice about education, career, and psycho-social matters, are required. Other aspects of diagnosis and management are discussed in Chapter 4.14.3.

(b) Kleine–Levin syndrome
This also usually begins in the teenage years with periods of excessive sleepiness alternating with periods of normality. The sleepy episodes are associated (in its classical form) with overeat-ing, hypersexuality, and other disturbed behaviours which are often bizarre and out of character. It is also frequently mistaken for a psychological disorder or other medical conditions. The condition should be distinguished from other causes of intermitt ent sleepiness
in young people such as substance abuse, major depressive disorder 
(in which the sleepiness is much less marked), menstruation-related hypersomnia, and certain neurological disorders.
Main sleep problems: parasomnias

This category of sleep disorders is described in Chapter 4.14.4 in relation to adult psychiatry. The present account emphasizes aspects of the parasomnias of particular importance in childhood and adolescence when, collectively, they are more common than in adult life. Frequently, parasomnias cause parents much concern and they appear to be the subject of considerable diagnostic confu-sion and delay. As in older patients, different types of parasomnia may co-exist. A detailed account of parasomnias in young patients is available elsewhere.
(8)
The following general points about childhood parasomnias have 
clear implications for clinical practice.

(8)
◆ Precise diagnosis is important as different parasomnias may well need contrasting types of treatment. Accurate diagnosis depends principally on a detailed account of the subjective and objective sequence of events from the onset of the episode to its resolution, as well as the circumstances in which the episode occurs, including its timing. Audio–visual recording (including the use of home video systems) can be very informative. Only occasionally is PSG required, although this can be instructive where clinical evaluation is inconclusive and, sometimes, where there is the possibility that another type of sleep disorder co-exists.
◆ The more dramatic forms of parasomnia seem to be a particular cause of diagnostic confusion and imprecision, and also quite possibly unnecessary concern about their psychological signiﬁ  -
cance as most are benign.

◆ Especially when the range and manifestations of sleep disorders is not appreciated, parasomnias (and other sleep disorders) may well be misinterpreted as other physical or psychological conditions.9.2.9 sleep disorders in children and adolescents

SECTION 9  child and adolescent psychiatry 1702
◆ A child may have more than one kind of parasomnia or, indeed, 
more than one sleep disorder (e.g. arousal disorders associated with obstructive sleep apnoea).
◆ As many childhood primary parasomnias remit spontaneously within a few years, children and parents can often be reassured about the future, although protective measures (e.g. in severe headbanging or sleepwalking) may be required in the meantime.
◆ Speciﬁ  c treatment, including medication, is needed in only a 
minority of cases of primary parasomnia but is likely to be required for the underlying disorder in many of the secondary parasomnias.
◆ Research information on this point is limited, but a primary parasomnia might be symptomatic of a psychological problem if it is very frequent, unusually late in onset or persistent, or associated with a traumatic experience.

◆ Parasomnias may lead to psychological complications if the child is frightened, embarrassed, or otherwise upset by the experience, or because of the reactions of other people to the episodes.
Primary parasomnias
◆ Sleep-related rhythmic movement disorders  such as head-
banging, occur in many young children, almost always remitting spontaneously by 3 to 4 years of age. Although alarming to parents, they are usually of no psychological signiﬁ  cance (unlike 
daytime headbanging associated with severe neurodevelopmen-tal disorder). However, protective measures, such as padding the cot-sides, may be needed.
◆ Hypnagogic  (sleep onset) and hypnopompic  (on waking) 
hallucinations are common and may be frightening to the child.
◆ Parents are often distressed to witness confusional arousals, 
agitated sleepwalking , or sleep terrors  which are a form of 
‘partial arousal disorder ’ common in young children (see

‘partial arousal disorder ’ common in young children (see 
Chapter 4.14.4 for an account of arousal disorders). The degree of agitation and confused behaviour may be extreme, suggesting that the child is suffering in some way. In fact, in arousal disor-ders the child remains asleep and unaware of the events. Understandable attempts to arouse the child and provide comfort should be discouraged, as this may cause real distress. Although violence during sleep is described mainly in sleepwalking adults, such behaviour can occur in children.
◆ The term ‘nightmare’ is sometimes used misleadingly for any form of dramatic parasomnia. True nightmares  (frightening 
dreams) are common. If frequent and associated with intense bedtime fears, they may indicate an anxiety disorder and their content may suggest a cause.

◆ Nocturnal enuresis  is very common, affecting about 5 per cent 
of 7-year-olds at least once a week. Delayed maturation often seems to be the explanation, but physical or psychological factors may be involved, especially where previous bladder control is lost. Behavioural treatment can be very effective.
Secondary parasomnias
Nocturnal epileptic seizures  are not uncommon in children and 
must be distinguished from primary parasomnias because of their different signiﬁ  cance, and also the investigation and treatment they 
require. Seizures which are behavioural in manifestation are the most likely to be misdiagnosed as non-epileptic, for example benign centro-temporal (Rolandic) epilepsy of childhood and nocturnal frontal lobe seizures both of which are closely related to sleep.

Other parasomnias , which are part of medical or psychiatric 
disorders and which may be encountered in patients of any age, include nocturnal asthmatic attacks with accompanying distress, those associated with OSA or gastro-oesophageal reﬂ  ux, panic 
attacks, nocturnal disturbance that is part of the post-traumatic stress disorder, and dissociative states. Simulated parasomnias, shown by PSG to be enacted during wakefulness, can sometimes occur in children.
Stores, G. (2008). Sleep problems in children and adolescents: the facts . Oxford 
Stores, G. and Wiggs, L. (2001). Sleep disturbance in children and adolescents 
with disorders of development: its signiﬁ  cance and management . Clinics 
in Developmental Medicine No. 155. Mac Keith Press, London.
 1. Stores, G. (2007). Clinical diagnosis and misdiagnosis of sleep 
disorders. Journal of Neurology, Neurosurgery and Psychiatry ,

 2. Owens, J.A., Spirito, A., and McQuinn, M. (2000). The children’s sleep 
habits questionnaire. Psychometric properties of a survey instrument 
for school-aged children. Sleep ,23, 1043–51.
 3. Kuhn, B.R. and Elliot, A.J. (2003). Treatment efﬁ  cacy in pediatric sleep 
medicine. Journal of Psychosomatic Research ,54, 587–97.
 4. Fleming, P ., and Blair, P .S. (2007). Sudden infant death syndrome. Sleep 
Medicine Clinics, 2, 463–76.
 5. Fallone, G., Owens, J.A., and Deane, J. (2002). Sleepiness in children: 
clinical implications. Sleep Medicine Reviews ,6, 287–306.
 6. Dahl, R.E. and Lewin, D.S. (2002). Pathways to adolescent health: 
sleep regulation and behavior. Journal of Adolescent Health ,31,
175–84.
 7. Stores, G. (2006). The protean manifestations of childhood narcolepsy

175–84.
 7. Stores, G. (2006). The protean manifestations of childhood narcolepsy 
and their misinterpretation. Developmental Medicine and Child 
Neurology ,48, 307–10.
 8. Stores, G. (2007). Parasomnias of childhood and adolescence. 
Sleep Medicine Clinics ,2, 405–17.
9.2.10 Suicide and attempted 
suicide in children and adolescents
David Shaffer, Cynthia R. Pfeffer, 
and Jennifer Gutstein*
Suicidal behaviour is a matter of great concern for clinicians who 
deal with the mental health problems of children and adolescents. The incidence of suicide attempts reaches a peak during the mid-adolescent years, and mortality from suicide, which increases steadily

1703
through the teens, is, in many countries, one of the leading causes of 
death at that age.
Historical review
Until the late 1950s, knowledge about youth suicide was drawn from unrepresentative case reviews, reviews of the demography of suicide drawn from death certiﬁ  cate data, and speculation about dynamics. 
The late 1950s saw the ﬁ  rst systematic psychological autopsy study 
among adults that demonstrated the importance of psychiatric dis-order as a proximal cause of most suicides.
(1) This was followed by 
similar studies on children and adolescents,(2–5) conﬁ  rming the asso-
ciation in adolescence. Starting in the mid-1960s, the incidence of suicide in young males began to rise in many countries.
(6) The rate 
of increase eventually stabilized in the late 1980s and, in many coun-tries, is now showing signs of falling.
(7) These changes stimulated 
efforts to develop methods of preventing youth suicide.(8–11).
A good deal is now known about which teenagers commit sui-

cide, less about who attempts it, and very little about the optimal management of suicidal adolescents. The number of randomized controlled trials designed to assess different forms of treatment is exceedingly small, and many suggestions for clinical management are based on anecdotal accounts rather than on ﬁ  ndings from 
well-designed experimental trials.
Completed suicide occurs most commonly in older adolescents, and, although it can also occur in children as young as 6 years of age, it is excessively rare before puberty.
(7) Psychological-autopsy stud-
ies have shown that about 90 per cent of adolescent suicides occur in individuals with a pre-existing psychiatric disorder, often present for several years.
(3–5) In teenagers, the most common disorders are

(3–5) In teenagers, the most common disorders are 
some form of mood disorder, substance and/or alcohol abuse, often comorbid with a mood disorder in boys over age 15, and anxiety disorders.
(3, 4) At a trait level, many suicide completers have been 
noted to be irritable, impulsive, volatile, and prone to outbursts of aggression. However, this pattern of behaviour is by no means uni-versal, and anxious suicides have usually shown no evidence of prior behavioural, academic, or social disturbances.
(3)
Although some adolescents—predominantly girls suffering from 
a major depressive disorder—appear to have thought about suicide for some time before death, most adolescent suicides appear to impulsively follow a recent stress event, such as getting into trouble at school or with a law-enforcement agency; a ruptured relation-ship with a boy- or girlfriend; or a ﬁ  ght among friends. In many

instances, these stress events can be seen as a by-product of their underlying psychiatric disorder.
(12)
It also appears that a completed suicide can be precipitated—in a 
presumably already suicidal youth-by exposure to news of another person’s suicide, or by reading about or viewing a suicide portrayed in a romantic light in a book, magazine, or newspaper.
(13)
About a third of completed suicides have made a previous known 
suicide attempt, more commonly girls and those who suffered from a mood disorder.
(3) Completed suicide must be distinguished 
from autoerotic asphyxia, which is rare in teenagers.(3) Suicide 
pacts, common between middle-aged or elderly married couples and/or other family members, are similarly rare in adolescents, but are not unknown.
(3)Non-lethal suicidal behaviour
(a) Suicidal ideation

Suicidal ideation includes thoughts about wishing to kill oneself, making plans of when and where, and having thoughts about the impact of one’s suicide on others. Such thoughts may occur without great signiﬁ  cance among young children, who may not 
appreciate that suicide may result in irreversible death.
(14) However, 
appreciation of the ﬁ  nality of death should not be a factor in 
judging the seriousness of suicidal ideation. Suicide threats made by young children and adolescents most often involve a threat to jump out of a window, to run into trafﬁ  c, or to stab himself or 
herself.
(b) Attempted suicide
The most common proﬁ  le of a teenaged attempter is a 15- to 
17-year-old girl who has taken a small- or medium-sized overdose of an over-the-counter analgesic or medication taken by another family member. The behaviour is usually impulsive and occurs in the context of a dispute and humiliation with family or a boyfriend.

(15) The clinical features most strongly associated with 
suicide attempts are irritability, agitation, threatening, violent, or psychotic behaviour, and a persistent wish to die.
(16)
Groups in whom suicide attempts appear to be common include 
runaways,(3) children who have been exposed to physical and 
sexual abuse, and homosexual teenagers.(17) However, study-design 
issues make it unclear whether this is because of a high rate of psychopathology or substance abuse in these groups or because of some factor that speciﬁ  cally predisposes to suicidal behaviour.
A subset of non-fatal suicidal behaviour involving ingestion with 
a non-lethal intent is sometimes referred to as parasuicide. However, intent is difﬁ  cult to gauge retrospectively, and not all teenagers 
are aware of the lethalness of an ingestion, so that this term carries with it a risk of complacency and is probably best avoided in teenagers.
Suicide attempts

Assessment of a suicide attempt involves an evaluation of the short-term risk for suicide and attempt repetition, and an assess-ment of the underlying diagnosis or other promoting factors. If the child or teenager has been referred to as an ideator, it is important to determine whether they are contemplating or have secretly attempted suicide.
Repeated attempts, attempts by unusual methods (other than 
ingestions or superficial cutting), medically serious attempts, and attempts where the patient has taken active steps to prevent discovery all increase the risk for further attempts or death.
(18,19)
Children and adolescents systematically overestimate the lethality of different suicidal methods, so that a child with a signiﬁ  cant 
degree of suicidal intent may fail to carry out a lethal act.
(20–22)

(20–22)
The mental states leading to suicidal behaviour include anticipa-
tory anxiety, pessimism, or hopelessness, as well as paranoid or other cognitive distortions arising from an underlying psy-chiatric diagnosis.
(23) Inappropriate coping styles (e.g. impulsivity 
or catastrophizing) in response to external stress may also contrib-ute to the behaviour. Motivating feelings may include the wish to effect a change in interpersonal relationships, to rejoin a dead 9.2.10 suicide and attempted suicide in children and adolescents

SECTION 9  child and adolescent psychiatry 1704
relative, to avoid an intolerable situation, to get revenge, or to gain 
attention.(22)
Classiﬁ  cation of associated diagnoses
Suicide
Psychiatric diagnoses commonly associated with a suicide include 
depression, bipolar disorder, substance abuse, conduct disorder, 
and overanxious and panic disorders.(3–5) Although the rate of 
suicide in schizophrenics is high, because of the rarity of the 
condition, it accounts for very few suicides.
Recurring suicidal behaviour has been associated with hypomanic 
personality traits and cluster B personality disorders.(22) A history 
of impulsivity, mood lability, with rapid shifts from brief periods 
of depression, anxiety, and rage to euthymia and/or mania—
associated with transient psychotic symptoms, including paranoid 
ideas and auditory or visual hallucinations-is associated with a risk 
for further suicide attempts and is compatible with the diagnosis of

for further suicide attempts and is compatible with the diagnosis of 
borderline personality disorder. Many of these symptoms are also 
features of bipolar mood disorder.
(a) Age
In the United States, the age-speciﬁ  c mortality rate from suicide for 
10- to 14-year-olds was 1.6 per 100 000 in 1997.(24) This age group 
accounts for 7 per cent of the population but only 1 per cent of all 
suicides, and most of these occur in 12- to 14-year-olds.
The comparable figures for 15- to 19-year-olds are about 
six times higher. The suicide rates at this age in the United States and 
Canada in 1997 were 9.5 per 100 000 and 12.86 per 100 000 respec-
tively.(7) The proportion of suicides that occur in this age group is 
about the same as its representation in the general population.
Suicide rates for 15- to 24-year-olds in some other English-

speaking countries were 11.0 for males and 2.2 for females in the 
United Kingdom (1995), 16.0 in Australia (1995), and 26.1 in 
New Zealand (1997) (all per 100 000 population).(7)
(b) Gender
In the United States and most other countries, male suicides 
outnumber female suicides among 15- to 24-year-olds by a ratio 
of 4:1. In China and Cuba, the suicide rate is higher in females than 
in males.(7)
(c) Cultural and ethnic differences
Rates of suicide vary considerably in different cultural and national 
groups.(7) Possible reasons include variable access to lethal methods, 
different degrees of social support, integration, or group adher-
ence, or the inﬂ  uence of religious beliefs or spirituality.(25–27)
In some instances, the differences may be a function of geography

In some instances, the differences may be a function of geography 
rather than culture. Contagion within isolated groups may deter-
mine differences in rates.
(d) Secular changes
From 1964 to 1995, the suicide rate in the United States and Canada 
among 15- to 19-year-old males increased almost three-fold, and 
similar increases were reported in Australia, New Zealand, and the United Kingdom.(7) In most of these countries, there was little 
change in the female rate or in the rate amongst 10- to 14-year-olds. 
Fluctuations in the suicide rate appear to be real, rather than due to 
any methodological artefact (e.g. changes in reporting practices). 
The most plausible reason for the increase in suicidal behaviour 
among teenage boys is an increase in alcohol and substance use in 
the youth population.(3) The reasons offered for the recent decline 
in suicide rates include lowered substance- and alcohol-use rates

in suicide rates include lowered substance- and alcohol-use rates 
among the young and more effective diagnosis and treatment.(28)
Attempted suicide
There is a strong inverse relationship between attempted suicide 
and age. A large epidemiological survey of four suicide-related 
behaviours (ideation, plan, gesture, and attempt) in the United 
States has shown a signiﬁ  cantly higher rate of all four behaviours in 
the youngest age group (15–24 years).(29) This study also compared 
rates of these four behaviours across two decades (1990–1992 and 
2001–2003). It found that rates did not decrease, despite a 
dramatic increase in pharmacologic treatment.
Suicide attempts in adolescents are at least twice as common in 
females as males (see Figs 9.2.10.1 and 9.2.10.2). Considerable 
ethnic variation is seen in the United States, with, for unknown

ethnic variation is seen in the United States, with, for unknown 
Fig. 9.2.10.1 Youth risk behaviour survey: prevalence of suicidal ideation in 
teenagers in the previous 12-month period (1997) broken down into gender and 
ethnicity. (Reproduced from Centers for disease control (1998). Attempted suicide 
among high-school students–US, 1997. Morbidity and Mortality weekly Report, 
47, 47–9, copyright 1998, centers for Disease Control and Prevention, US.)
Fig. 9.2.10.2 Youth risk behaviour survey: prevalence of suicide attempts in 
among hign-school students–US, 1997. Morbidity and Mortality weekly Report, 

1705
reasons, Hispanic high-school students having twice the rate of 
black or white teenagers.(30)
Aetiology
(a) Psychiatric disorders
The most important risk factor for suicide is a psychiatric disor-der.
(3) Controlled studies of completed suicide suggest similar risk 
factors for boys and girls,(3, h31) but with marked differences in their 
relative importance(3–5) (Table 9.2.10.1). In girls, major depression 
is the most powerful risk factor, which, in some studies, increases the risk of suicide 12-fold; followed by a previous suicide attempt, which increases the risk approximately three-fold. In boys, a previ-ous suicide attempt is the most potent predictor, increasing the rate over 30-fold. It is followed by depression (12-fold increase), disruptive behaviour (two-fold increase), and substance abuse (increasing the rate by just under two-fold).
(3)
(b) Psychosocial stressors
Stressful life events often precede a suicide and/or suicide attempt.

(3)
(12) They are rarely a sufﬁ  cient cause in suicide, and their 
importance seems to lie in their action as a precipitant of stress in young people who are at risk by virtue of their psychiatric condi-tion. Family discord, lack of family warmth, and a disturbed par-ent-child relationship are commonly associated with types of child and adolescent psychopathology, but these factors do not play a more important role in suicide.
(12)
(c) Cognitive factors
Perceptions of hopelessness, negative views about one’s own competence, poor self-esteem, a sense of responsibility for negative events, and the immutability of these distorted attributions may 
contribute to the ‘hopelessness’ repeatedly found to be associated with suicidality.
(18, 19)
(d) Biology
Biological factors, speciﬁ  cally dysregulation of the serotonergic 
system, are common in adult suicides.(32) Dysregulation is mani-

(18, 19)
fested by low levels of serotonin metabolites in central nervous system fluids, low concentrations of presynaptic serotonergic receptors, and dense concentrations of postsynaptic receptors. Such serotonin abnormalities have been localized to the ventrolateral prefrontal cortex and brainstem of suicide victims and attempters (in postmortem positron-emission tomographic studies as well as in in vivo  biological challenges).
(33) Serotonin may inhibit 
extreme ﬂ  uctuations of mood and reactivity, and the vulnerability

extreme ﬂ  uctuations of mood and reactivity, and the vulnerability 
to suicide of individuals with these biological abnormalities may be mediated by impulsivity and emotional volatility. As the ventral prefrontal cortex plays a role in behavioural inhibition, it is conceivable that serotonin irregularities in this area make it more difﬁ cult for a suicidal individual to control his suicidal impulses.
(33)
The frequency with which these biological ﬁ  ndings occur in ado-
lescent suicide attempters is not yet clear, and studies to demon-strate the precise behavioural correlates of serotonin dysregulation proﬁ les are still lacking. Nordstrom et al .
(34) have suggested that 
knowing the biological status of suicide attempters may have a practical value, in that low 5-hydroxyindole acetic acid concen-trations in cerebrospinal ﬂ  uid examined shortly after a suicide

knowing the biological status of suicide attempters may have a practical value, in that low 5-hydroxyindole acetic acid concen-trations in cerebrospinal ﬂ  uid examined shortly after a suicide 
attempt may differentiate between suicide attempters who will commit suicide or repeat the attempt within a year and those who will not. The biology of suicidal behaviour is considered more fully in chapter 4.15.3
Table 9.2.10.1 Psychiatric diagnoses in child and adolescent suicides
Martunnen et al .(5)Shaffer et al.(6)Brent et al.(4)
Country Finland USA USA
Area National Greater New York Western PennsylvaniaPeriod 1987–1988 1984–1986 1984–1994N 53 120 140
Age 13–19 <20 13–19
Percentage girls 17 21 15
Control group None Matched community Matched communityDiagnostic system DSM-IIIR DSM-III DSM-III
Males Females All Males Females All Males Females All
Any diagnosis (%) 93 100 94 90 92 91 82 81 82Any mood disorder (%) 48 67 51 60 68 61 43 71 47
Substance abuse (%) 27 44 30 42 12 35 35 24 34

Conduct/antisocial/ 18 11 17 54 36 50 35 10 31
 disruptive disorder (%)
Any anxiety disorder (%) 2 11 4 27 28 27 13 24 14Schizophrenia (%) 5 11 6 3 4 3 — — —Past suicide attempt 27 67 34 28 50 33 37 62 419.2.10 suicide and attempted suicide in children and adolescents

SECTION 9  child and adolescent psychiatry 1706
(e) Imitation
Evidence has accumulated indicating that suicide in vulnerable 
teenagers can be precipitated by exposure to real or ﬁ  ctional 
accounts of suicide, such as intense media coverage of a real suicide 
or the ﬁ  ctional representation of a suicide in a popular ﬁ  lm or 
television programme. The risk is especially high in the young, and 
lasts for approximately 2 weeks.(13) The phenomenon of suicide 
clusters is also presumed to be related to imitation.
“Cybersuicide,” or a tendency for internet sites such as Bebo or 
MySpace” to encourage suicide pacts or to increase completed 
or attempted suicide in vulnerable adolescents, has become an 
increasing concern. This concern is based on multiple case reports 
from Japan, Wales, and the United States. These have captured sub-
stantial media attention. As yet no objective empirical data have 
been amassed to determine if there is a causal relationship between

been amassed to determine if there is a causal relationship between 
internet use and youth suicide.
One hypothetical model for how biological and social factors 
ﬁ t together is illustrated in Fig. 9.2.10.3.
In a longitudinal study of a large African-American community 
in the United States, Juon and Ensminger(35) found risk factors for 
suicidal behaviour in African-Americans to be very similar to those 
found in Caucasians (depression, substance use, and a number of 
family variables).
Little is known about the natural history of suicidal behaviour, but 
early-onset suicidal behaviour in prepuberty predicts suicidal 
behaviour in adolescence(36, 37) and an early-onset major depressive 
disorder is associated with suicidal behaviour in adolescence and 
adulthood.(38) Attempts to predict, at the time of the ﬁ  rst attempt,

adulthood.(38) Attempts to predict, at the time of the ﬁ  rst attempt, 
which adolescents are likely to repeat their suicidal behaviour have 
been unsuccessful.(22)
Because of the need to respond to a suicidal crisis, it is desirable to 
offer treatment within a service-delivery system that includes inpa-
tient and outpatient settings, acute crisis work, stabilization, 
extended management, and follow-up care and monitoring.
Outpatient treatment  should be used when the child or adoles-
cent is unlikely to act on suicidal impulses, when there is sufﬁ  cient 
support at home, and when there is someone who can take action if 
the adolescent’s behaviour or mood deteriorates. Children and 
adolescents should never be discharged from an emergency or care 
service without the child’s or adolescent’s caretaker having been 
interviewed (see Box 9.2.10.1) to ensure that ﬁ  rearms and/or lethal

interviewed (see Box 9.2.10.1) to ensure that ﬁ  rearms and/or lethal 
medications will be made inaccessible to the child. Unless this 
advice is given, parents will rarely, on their own initiative, take the 
necessary precautions. Before discharge, the clinician must have 
a good understanding of the amount of support that will be avail-
able for the child or adolescent if he or she is discharged home.
Acute psychiatric inpatient care  should be reserved for patients 
for whom intensive surveillance and intervention are considered 
essential-as in the presence of active suicidal ideation and intent 
or when the youngster is unable to commit to not carrying out a 
suicidal act, when the youth is unpredictable, impulsive, agitated, 
or psychotic, or if there is a lack of support and supervision in the home. There is no evidence that exposure to other suicidal psychi-

atric inpatients increases the risk of suicidal behaviour. Determining 
when a patient is ready for discharge from the hospital or crisis 
centre will usually include an evaluation of the severity of existing 
suicidal ideation and intent. Implicit coercions (e.g. telling patients 
that discharge will be delayed until they can state that they are not 
suicidal) should be avoided.
Treatment compliance may be improved by offering deﬁ  nite, 
closely spaced, follow-up appointments, being ﬂ  exible in arranging 
appointments if a crisis should arise, and reminding the family 
and patient by telephone or note about the next appointment. If an 
appointment is missed, the patient and parent should be contacted. 
Hopeless and depressed children and adolescents, who may be not 
be able to commit to a lengthy treatment process, may be better

be able to commit to a lengthy treatment process, may be better 
engaged by offering short-term treatment plans with defined 
intervention goals. While offering conﬁ  dentiality for some issues, 
Fig. 9.2.10.3 How do suicides occur and how can they be prevented?

1707
it is essential that the clinician communicate to the patient that, 
if they feel that suicidal thinking or behaviour is imminent, such information will be shared with the parents.
Contracts
A written or verbal ‘no-suicide’ contract is commonly negotiated at the start of treatment in the hope that it will improve treatment com-pliance and reduce the likelihood of further suicidal behaviour.
(39)
In its usual form, the child or adolescent promises not to engage in suicidal behaviour without ﬁ  rst informing the parents, therapist, or 
other responsible adult when he or she has thoughts of suicide or plans to commit suicide. No empirical studies have evaluated the efﬁ cacy of a contract, and contracts should be seen as no more than

adjuncts to the management of patients with low intent. Even if the patient agrees to such a contract, suicide risk may persist. It should also be appreciated that a ‘no-suicide’ contract may lessen a patient’s communication of stress and dysphoria, decrease the potential for developing a therapeutic alliance, and impair risk management. As mentioned above, coercive communications should be avoided, because these may encourage deceit and deﬁ  ance.
Speciﬁ  c psychotherapies
Working with suicidal children and adolescents is best done by 
a clinician who is available, has skill and training in managing suicidal crises, relates to the patient in an honest and consistent way, and can convey a sense of optimism and activity. Given these personal attributes, the therapist may use various models of psy-chotherapy, although relatively few empirical studies have evaluated their efﬁ  cacy.
(a) Cognitive behavioural therapy
Cognitive hbehavioural therapy is effective in depressed teenag-

ers,(40) but its value for suicidal adolescents has not been demon-
strated.(23) Brent et al .(23) modiﬁ  ed the approach for depressed 
adolescents. The treatment comprized 12 to 16 once-weekly sessions, followed by a 6-month booster phase of monthly or bimonthly sessions. It included a psychoeducational manual about mood disorders, training to monitor and modify automatic thoughts, assumptions, and beliefs, training in more assertive and direct methods of communicating, and help in conceptualizing alternative solutions to problems. Meetings with parents were sometimes held to augment the treatment, and psychopharmacol-ogy was used adjunctively if depressed adolescents had not improved after 4 to 6 weeks of pharmacotherapy.
Brent’s study provides no evidence of the efﬁ  cacy of cognitive-

Brent’s study provides no evidence of the efﬁ  cacy of cognitive- 
behavioural therapy for teenagers who had made a suicide attempt who were not included in this study.(b) Dialectical behavioural therapy
Dialectical behavioural therapy ( DBT ) is the only form of psycho-
therapy that has been shown in a randomized control trial to reduce suicidality in adults with borderline personality disorder.
(41) This 
treatment is based on a biosocial theory in which suicidal behav-iours are considered to be maladaptive solutions to painful negative emotions that also have affect-regulating qualities and elicit help from others.
(41)
The treatment involves developing problem-oriented strategies

(41)
The treatment involves developing problem-oriented strategies 
to increase distress tolerance, emotion regulation, interpersonal effectiveness, and the use of both rational and emotional input to make more balanced decisions. It usually involves individual and group sessions over the course of a year, although an untested modiﬁ  cation for adolescents (DBT-A) is designed to take 12 we eks.
(42)
It involves the participation of a relative who is charged to improve 
the home environment and to teach other relatives how to model and reinforce adaptive behaviours for the adolescents.
(c) Family therapy

As indicated above, family discord, poor communication, disagree-ments, lack of cohesive values and goals, and irregular routines and activities are common in suicidal children and adolescents who often feel isolated within the family. Family intervention aims to decrease such problems, improve family problem-solving and conﬂ  ict resolution, and reduce blame directed at the suicidal child 
or adolescent. Family-based cognitive therapy aims to reframe the family’s understanding of their problems, to alter the family’s maladaptive problem-solving techniques, and to encourage posi-tive family interactions. Psychoeducational approaches can help parents clarify their understanding of childhood and adolescent suicidal behaviour, identify changes in mental state that may herald a repetition, and reduce the extent of expressed emotion or anger.
(31)

(31)
Psychopharmacological interventions
In meta-analyses of adult studies, lithium maintenance treatment greatly reduces (8.6-fold) the recurrence of suicide attempts in adults with bipolar or other major affective disorders. Further, when lithium is discontinued there is a seven-fold increase in the rate of suicide attempts and a nine-fold increase in the rates of 
suicide.
(43) Other mood stabilizers, such as valproate and 
carbamazepine, are also widely used to treat bipolar disorders in children and adolescents; although their efﬁ  cacy has yet to be 
empirically demonstrated. Depressed suicidal children and adoles-cents with a history of bipolar disorder should ﬁ  rst be treated with 
a mood stabilizer before receiving an antidepressant.
Studies in depressed adults have found that the selective serot-
onin reuptake inhibitor ( SSRI ) antidepressants reduce suicidal

onin reuptake inhibitor ( SSRI ) antidepressants reduce suicidal 
ideation, and also reduce the frequency of suicide attempts in non-depressed patients with cluster B personality disorders with a past history of suicide-attempt behaviour.
(44) In contrast to the highly 
lethal potential of tricyclic antidepressants when taken in overdoses, SSRIs have low lethal potential. In a controlled trial of the depot neuroleptic ﬂ  upenthixol, Montgomery and Montgomery
(45) noted 
a signiﬁ  cant reduction in suicide-attempt behaviour in adults who 
had made numerous previous attempts. Similar studies have yet to be conducted for adolescents.
In the past decade, there has been much controversy over 
whether the SSRI antidepressants can induce suicidal ideation Box 9.2.10.1 Checklist before discharging an adolescent who has 

Before discharging a patient from the emergency room or 
crisis centre, always:
◆Check that ﬁ rearms  and lethal medications  have been secured 
or removed
◆Check that there is a supportive person  at home
◆Check that a follow-up appointment  has been scheduled9.2.10 suicide and attempted suicide in children and adolescents

SECTION 9  child and adolescent psychiatry 1708
and/or behaviour. A number of case reports appeared in 1990 
describing patients who had developed suicidal preoccupations after starting treatment with ﬂ  uoxetine. These reports were not 
supported by meta-analyses and re-analyses of large SSRI-treat-ment trials of depressed, bulimic, or anxious patients.
(46,47) The 
conclusion was reached that suicidal ideation is a common feature of depression and that the prevalence in SSRI-treated depressives was no greater than expected.
However, one reanalysis of the data presented in certain of these 
studies suggested that new ideation was signiﬁ  cantly more com-
mon in SSRI-treated depressed patients who had not previously reported suicidal ideation. Further, in a naturalistic challenge study, Rothschild and Locke
(48) were able to reinduce suicidal ideas in 
a small series of patients who had ﬁ  rst experienced ideation after

a small series of patients who had ﬁ  rst experienced ideation after 
starting treatment with ﬂ  uoxetine. These patients had also experi-
enced akathisia as a complication of ﬂ  uoxetine treatment, and 
a relationship between suicidality and ﬂ  uoxetine-induced akathisia 
has been noted by others.
Several meta-analyses have shed some additional light on this 
complex issue. A British meta-analysis of 702 clinical trials involv-ing 87, 650 adult patients documented a two-fold increase in suicide attempts in patients receiving SSRIs as compared to placebo.
(49)
An American meta-analysis of pediatric patients used data from 23 trials involving 4 582 patients.
(50) This study also found an

(49)
(50) This study also found an 
increased risk of suicidality in patients taking SSRIs, after controlling for the risk associated with suffering from depression. Both British and American regulatory agencies now require warnings about suicidal risks associated with SSRIs. (See also chapter 9.5.5)
At this stage, the wisest course of action is for the practitioner 
to be particularly observant during the early stages of ﬂ  uoxetine 
treatment of a depressed adolescent, to systematically enquire about suicidal ideation before and after treatment is started, and to be especially alert to the possibility of suicidality if SSRI treatment is associated with the onset of akathisia.
One must be careful about the risk of inducing suicidal ideation 
or behaviour through psychopharmacological activation or 
disinhibition. Clinicians should be cautious about prescribing

disinhibition. Clinicians should be cautious about prescribing 
medications that may reduce self-control, such as the benzodi-azepines, and phenobarbitone (phenobarbital). These drugs also have a high lethal potential if taken in overdose. Montgomery
(51)
noted that benzodiazepines may disinhibit some individuals who then become aggressive and attempt suicide and that there are suggestions of similar effects from the antidepressants, maprotiline and amitriptyline, the amphetamines, and phenobarbitone. Amphetamines or other stimulant medication should only be prescribed when treating suicidal children and adolescents with attention-deﬁ  cit hyperactivity disorder.
Community-based suicide prevention
The principal public health approaches to suicide prevention have 
been as follows:
◆ crisis hotlines
◆ method control

◆ media counselling to minimize imitative suicide◆ indirect case-finding by educating potential gatekeepers, 
teachers, parents, and peers to identify the ‘warning signs’ of an impending suicide
◆ direct case-ﬁ  nding among high-school or college students or 
among the patients of primary practitioners by screening for conditions that place teenagers at risk for suicide
◆ training professionals to improve the recognition and treatment 
of mood disorders.
(a) Crisis hotlines
Although crisis hotlines are available almost everywhere in the United States, research so far has been fairly limited and has failed to show that they impact on the incidence of suicide.
(52) Possible

(52) Possible 
reasons for this include the fact that actively suicidal individuals (males and individuals with an acute mental disturbance) do not call hotlines because they are acutely disturbed, preoccupied, or intent on not being deﬂ  ected from their intended course of action. 
It also seems that the large majority of callers are females, whereas males are at the greatest risk for suicide, that crisis lines are often busy and there may be a long wait before a call is answered so that callers disconnect, and that the advice that individuals receive on calling a hotline may be stereotyped, inappropriate for an individual’s needs, and perceived as unhelpful by the caller.
While each of these deﬁ  ciencies is potentially modiﬁ  able, to date 
there have been no systematic attempts to do so. Research studies in this area have been sparse and are sorely needed.
(b) Method restriction

Method preference varies by gender and by nationality. In the United States, the most common method for committing suicide is by ﬁ rearm, and it has been suggested that reducing ﬁ  rearm availa-
bility will reduce the incidence of suicide. However, in a natural experiment in the United Kingdom, when self-asphyxiation with coal gas became impossible after the introduction of natural gas, the decline in the suicide rate was marked but short-lived. There is, as yet, no good evidence that reducing access to ﬁ  rearms by 
gun-security laws has a signiﬁ  cant impact on suicides attributable 
to such, although they do impact on accidental and homicidal deaths from ﬁ  rearms.
(53)
(c) Media counseling
The United States Centers for Disease Control have issued sensible

(53)
The United States Centers for Disease Control have issued sensible 
guidelines for reporters and editors, pointing to the risks of exag-gerated or prominent coverage of youth suicide in general, and of the risks in focusing attention on an individual suicide.
(11) These 
sensible guidelines should be known to child clinicians who are engaged in public-health practice, even though there is, as yet, no good evidence that their application is effective in reducing the suicide rate.
(d) Indirect case-ﬁ  nding through education
Controlled studies have failed to show that classes for high-school 
students about suicide increase students’ help-seeking behaviour when they are troubled or depressed.
(54) On the other hand, there 
is evidence that previously suicidal adolescents are perturbed by exposure to such classes.
(51) Such educational programmes

(51) Such educational programmes 
seem, therefore, to be both an ineffective mode of case-ﬁ  nding and 
to carry with them an unjustified risk of activating suicidal thoughts. Educational approaches in schools are dsicussed further in chapter 4.15.4

1709
(e) Direct case-ﬁ  nding
If asked in a non-threatening way, adolescents will provide accurate 
information about their own suicidal thoughts and/or behav iours.(21)
Therefore a sensible approach to suicide prevention is to systemati-
cally screen 15- to 19-year-olds (the age group at greatest risk) for previous suicide attempts, recent serious suicidal preoccupations, depression, or complications of substance or alcohol use. Y ouths identiﬁ  ed in this way should be referred for evaluation and, if 
necessary, treatment.
(f)  Training primary care physicians and gatekeepers in the 
recognition and treatment of mood disorders
Preliminary and, as yet, unreplicated studies in Sweden(55) suggest 
that education of primary practitioners to identify the characteris-tics of mood disorders better and to treat these effectively produced a signiﬁ  cant reduction in suicide and suicide-attempt rates in

women. Because the optimal treatment of adolescent depression is not as well understood as that of adult depression, this is an option that may prove to be useful, but further work is needed.
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Affective Disorders ,35, 147–52.
9.2.11 Children’s speech 
and language difﬁ  culties
Judy Clegg

Judy Clegg
Speech and language difﬁ  culties have a signiﬁ  cant impact on 
the lives of children and their families. This chapter will give an overview of the types of speech and language difﬁ  culties chil-
dren present with and how these are generally classiﬁ  ed and 
diagnosed. Speciﬁ  c Language Impairment (SLI) and speech and 
language difﬁ  culties associated with child psychiatric disorder, 
speciﬁ  cally disorders of attention and selective mutism will be a 
focus. The life course of children with speech and language impairments will be described through childhood, adolescence, and adult life. Current management approaches will be present-ed and evaluated and strategies for effective communication considered.
Typical speech and language development

It is remarkable how quickly and easily most children progress through the typical stages of speech and language development to become competent communicators by the age of 5 years. Much is known about how children acquire speech and language and when these skills are achieved.
(1) Children need to be competent commu-
nicators prior to starting school, as learning is dependent on adequate speech and language abilities. At school entry age, children are expected to be able to speak clearly, to understand and use complex grammatical structures, to use language for a range of communicative reasons from requesting to negotiating and predicting, to take part conﬁ  dently in conversations with both 
children and adults and to have a knowledge of letter names and sounds and to read some single words. The acquisition of these speech and language skills will enable the child to access the

1711
 educational curriculum where learning is dependent on both ver-
bal and written language. If children are not competent in these skills then they will experience signiﬁ  cant difﬁ  culties in their learn-
ing from the start of their school career.
Features of speech and language difﬁ  culties
Speech and language development can be affected by hearing 
impairment, visual impairment, general learning disability, epilepsy, and speciﬁ  c syndromes of learning disability such as Down’s 
syndrome, and Fragile X syndrome. In these examples, speech and language difﬁ  culties are usually attributed to and explained by an 
aetiological cause. However, speech and language difﬁ  culties do 
occur in the absence of an obvious identiﬁ  able cause and are there-
fore considered as a speciﬁ  c impairment, e.g. SLI.
Prevalence rates of speech and language difﬁ  culties vary and 
are dependent on the criteria used to deﬁ  ne and classify them. Law 
et al.

et al.
(2) report prevalence rates in children as high as 24.6 per cent 
whereas rates for SLI are much lower between 3 and 7 per cent.(3)
Importantly, speech and language difﬁ  culties can persist over 
time and often have a negative impact on the child’s education and general well-being.
(a) Speech difﬁ  culties
A speech difﬁ  culty reduces a child’s intelligibility and may result in 
speech sounds being omitted, substituted with another sound or distorted. Speech difﬁ  culties can be evident when a child says single

speech sounds being omitted, substituted with another sound or distorted. Speech difﬁ  culties can be evident when a child says single 
words, sentences, and participates in conversation. The physical articulation of speech sounds is affected by physiological and struc-tural abnormalities, such as cleft lip/palate, and neurological impairments leading to dysarthria characterized by weakness and/or in-coordination of the speech musculature system. There is another group of children who have phonological speech difﬁ  culties. 
These children have an intact speech musculature system but have not managed to acquire all the speech sounds of their language and so can only use a limited range, which subsequently limits their intelligibility.
(b) Language difﬁ  culties
Language difﬁ  culties can involve problems in the development of 
both comprehension and production.
(i) Vocabulary difﬁ  culties
Restricted word knowledge and poor development of the under-

standing of word meanings result in small vocabularies. Some 
children have impoverished vocabularies but other children can have speciﬁ  c word ﬁ  nding or retrieval difﬁ  culties. Here, the child 
knows the word he wants to say but is unable to retrieve it accurately and quickly. This is usually evident by ‘searching’ behav-iours where the child may substitute the word for a related word, use a ﬁ  ller word such as ‘thingy’ or ‘stuff’ , gesture the word instead 
of saying it or say the ﬁ  rst sound of the word but not the rest. 
For example,
ICE SKATING: ‘I can’t do that thing . . . erm . . . you know . . . where 
you put sharp shoes on . . . I always fall over’ .
PLUM: ‘well, I don’t really like that one which smells like soil and is 
purple and juicy’

These problems may not only be due to lexical difﬁ  culties but also 
problems retrieving the right phonological sounds of the word. 
Cognitive impairments in information processing, speciﬁ  cally short-term and phonological working memory have been associat-
ed with problems in vocabulary learning.(4)
(ii) Syntax difﬁ  culties
Children often have difﬁ  culties in their understanding and use of 
syntax and as a consequence ﬁ  nd it very difﬁ  cult to not only under-
stand language but also to construct sentences in order to use lan-guage to communicate effectively, for example giving a narrative where past events are described and future events predicted. Common problems are learning how to use inﬂ  ections to mark dif-

ferent tenses and understanding as well as constructing complex sentences such as passives. The child in the following example has lots of syntax difﬁ  culties as well as word ﬁ  nding difﬁ  culties and it is 
clear how this affects his ability to convey verbal information. The correct forms the child is attempting are shown in brackets.
‘They erm . . . was . . . erm . . . goed to make (made) some vegetable 
circles (pizzas) and rolls (they rolled) it (the dough) out because that’s what you do ﬁ  rst and he was reading the menu (recipe) as 
well and then they is erm . . . erm . . . erm . . . printing (cut) them out and then they put them in the oven because they’ll taste crunchy (to cook) and then erm . . . then they took them out of the oven so they be . . . er . . . get . . . cool down (could cool down) and then you would take (ate) them’ .
(iii) Social communication difﬁ  culties
Children with speech and language difﬁ  culties often show associ-

ated problems in social communication behaviours, also referred to as pragmatics. These can be both verbal and non-verbal and include difﬁ  culties with eye contact, initiation, turn taking, interac-
tion, sharing, requesting, and responding. Higher level social com-munication abilities can also be affected such as inferring informa-tion, giving the listener adequate information and self-monitoring. Ultimately, these can all hinder effective communication between the child and others and also expose the child to negative social experiences, particularly with their peers. For some children, the social communication difﬁ  culties may be an intrinsic part of a 
developmental disorder where speech and language difﬁ  culties 
are evident, for example children with autistic spectrum disorders. In other children, it is important to note that these behaviours can

are evident, for example children with autistic spectrum disorders. In other children, it is important to note that these behaviours can 
develop as a secondary consequence of poor communication skills 
due to the speech and language difﬁ  culty.
Speech difﬁ  culties can occur in isolation without the presence of 
language difﬁ  culties. Language difﬁ  culties can also occur without 
the presence of speech difﬁ  culties but often speech and language 
difﬁ culties co-occur together. Children can have difﬁ  culties with 
both language comprehension and language production.
Within child psychiatry, both the ICD-10(5) and DSM-IV(6) sys-
tems categorize developmental speech and language difﬁ  culties. 
However, there is little robust empirical evidence to support the subtyping of speech and language difﬁ  culties. Children are usually 
classiﬁ  ed according to whether the speech and language difﬁ  culty is

classiﬁ  ed according to whether the speech and language difﬁ  culty is 
speciﬁ  c, i.e. cognitive development is age appropriate and if there 
are any co-morbid aetiological or functional explanations. Descriptions of the type of speech and language difﬁ  culty involve 
identifying how the speech and language system is disrupted, describing the levels of impairment, and how this is impacting on the child’s communication and their access to learning.9.2.11 children’s speech and language difficulties

SECTION 9  child and adolescent psychiatry 1712
Descriptions of developmental speech and 
language disorders
Children’s language is said to be ‘delayed’ when their language 
abilities are behind those expected for their chronological age and ‘impaired’ or ‘disordered’ when a language delay does not resolve and the child continues to experience signiﬁ  cant and severe prob-
lems. Several established diagnoses of developmental speech and language disorders are described below:
(a) Cleft lip and palate
A cleft/lip palate results from the incomplete fusion of the hard or soft palate in the embryonic stages of development. A cleft palate can be accompanied by a cleft lip or either one can occur independently. In the United Kingdom, cleft lip/palate is repaired in the ﬁ  rst few months of life. However, some children can be left 
with ﬁ  stulas and velopharyngeal incompetency, which signiﬁ  cantly

with ﬁ  stulas and velopharyngeal incompetency, which signiﬁ  cantly 
affects speech development and intelligibility. Children with cleft lip/palate receive speech and language therapy from birth onwards. At birth the focus of attention is primarily on feeding and then the development of speech and language.
(b) Dysarthria
Dysarthria is a speech disorder due to neurological impairment which affects how the speech musculature system functions. Children with cerebral palsy often have dysarthria, which makes their speech slow, weak, and uncoordinated. There may be a mild, slight slurring of speech to profound dysarthria where a child cannot produce any intelligible sounds or words. Children with moderate and severe dysarthria have shallow breathing which is insufﬁ  cient to sustain speech and/or a low-pitched voice, nasal 
speech, and a reduced range of vowels and consonants that can be produced accurately.
(c) Developmental phonological disorder

Unlike cleft lip/palate and dysarthria, phonological speech disor-ders involve the child’s developing speech sound or phonological system. The child’s speech is difﬁ  cult to understand because the 
child makes speech sound errors which are either due to the speech sound system developing more slowly or in an atypical way and this is not a result of obvious structural, sensory, or neurological impairments. Often, there are systematic patterns of errors in the child’s speech, for example the child always replaces the ‘s’ sound with a ‘d’ sound. Auditory processing and discrimination skills have been implicated in the development and maintenance of this disorder. Over time, phonological disorders often resolve with speech and language therapy input. However, for some children they are severe and do persist into adult life.
(d) Childhood apraxia of speech (CAS)

This developmental speech disorder is characterized by both speech and non-speech behaviours. The speech sound errors are inconsis-tent and are accompanied with oral movement difﬁ  culties in 
drooling, feeding, and blowing. Reduced early verbal behaviours such as babbling are often evident. CAS often co-occurs with motor apraxia but for some children, only speech and oral movements are affected. There is some debate as to the existence of CAS as there is no obvious cause although both neuromotor planning and the organization of the child’s phonological system have been implicated. CAS is often a label given to children where the speech 
disorder has persisted despite intervention and oral non-speech movements are affected. See Dodd
(7) for a detailed review of 
children’s speech disorders.
(e) Fluency disorders
Although classiﬁ  ed under speech disorders, stuttering is not an 
articulatory or phonological difﬁ  culty. There are no structural

articulatory or phonological difﬁ  culty. There are no structural 
abnormalities and the child usually has a typically developing phonological system. Core stuttering behaviours include part-word or whole-word repetitions, revisions, pauses, blocks, sound prolon-gations, and obvious struggling behaviours such as jerky head movements. Secondary behaviours result from the stuttering and generally help the individual to avoid stuttering. For example, circumlocution where the speaker substitutes a word he knows he will stutter on for an easier word and environmental control such as avoiding the use of the telephone or talking to certain people. Fluency disorders are often identiﬁ  ed in young children before the 
age of 5 years although many children experience a period of nor-mal non-ﬂ  uency usually between the ages of 2 and 5 years, which is

age of 5 years although many children experience a period of nor-mal non-ﬂ  uency usually between the ages of 2 and 5 years, which is 
not severe and resolves spontaneously.
(f) Learning disability
Level of cognitive ability is the strongest predictor of language ability and therefore language development is certainly affected in learning disability. The sequence of language development is simi-lar to that found in typical development but with mild to moderate to severe and profound delay. A child with a profound learning dis-ability may never develop an intent to communicate whereas another child may have established an intent but no verbal lan-guage and uses some signs or symbols to communicate instead. For children with mild and moderate learning disability, language abilities plateau with no further improvement, usually in adoles-cence at a level below the child’s chronological age.
It should be noted that speciﬁ  c patterns of speech and language

It should be noted that speciﬁ  c patterns of speech and language 
development have been identiﬁ  ed in speciﬁ  c syndromes of learning 
disability. Down’s syndrome is characterized by superior vocabu-lary development to grammatical development and children with William’s syndrome often appear as competent communicators but do have signiﬁ  cant language learning problems. Speech and 
ﬂ uency problems are common in learning disability and vary 
according to the aetiology of the learning disability. For example, conductive hearing loss and articulatory speech problems occur where there is cranio-facial involvement.
(g) Acquired childhood aphasias

Acquired aphasias refer to a loss or deterioration in language ability after a period of typical language development. The child acquires language but then loses these language abilities, usually between 3 and 7 years of age. Causes of childhood aphasia include open and closed head injury, cerebrovascular lesions, cerebral infections, cerebral tumours, and epilepsy. Landau Kleffner (ﬁ  rst described 
by Landau and Kleffner in 1957)
(8) is an acquired aphasia where 
language deteriorates after a period of typical language develop-ment and the deterioration in language is usually, although not always accompanied with a seizure disorder. Receptive language is severely affected with expressive language problems as well, often word ﬁ  nding difﬁ  culties. See Lees
(9) and Deonna(10) for a complete 
review.

1713
Speciﬁ  c language impairment (SLI)
Speciﬁ  c language impairment (SLI) is a term used to describe 
language impairment (and additional speech impairment) where there is no identiﬁ  able medical, neurological, sensory, or functional 
cause and where cognitive ability measured by non-verbal intelli-gence (IQ) is within the normal range. Therefore, there is a discrep-ancy between language and cognitive ability with the exclusion of any obvious causes for the language impairment. Diagnosis of SLI according to exclusionary and discrepancy criteria is dependent on standardized language and cognitive psychometric assessments. However, there is continuing debate regarding which criteria to use to establish a meaningful discrepancy between language and cogni-
tion. ICD-10,
(5) for example adopt a strict criteria of language skills

(5) for example adopt a strict criteria of language skills 
at least two standard deviations below the level expected for the child’s chronological age and language skills at least one standard deviation below the child’s level of non-verbal IQ. More liberal criteria advocates a non-verbal IQ of 75 or above with language abilities often only one SD below the mean. Proponents of liberal criteria claim that more stringent criteria may fail to identify chil-dren who are at risk of poor long-term outcomes. However, liberal criterion may identify children who simply perform at the lower end of the normal distribution of language ability. It should be recognized that different criteria are used. Although the diagnosis of SLI stipulates good cognitive ability, some speciﬁ  c cognitive 
deﬁ cits in phonological memory, verbal, and visuo-spatial memory 
and symbolic play are evident and thought to underpin the lan-guage impairment.

SLI is considered to affect 3–7 per cent of all children.
(3) The use 
of the exclusionary and discrepancy criteria to deﬁ  ne SLI means 
that as a group, children with SLI are very heterogenous with impairments in many areas of language. Although useful, attempts to subtype SLI
(11) have not yet proved clinically robust. However, 
children with SLI are considered to show disproportionate difﬁ  -
culties in vocabulary and syntax compared to other aspects of language.
(a) Aetiology of SLI
Research in SLI primarily focuses on trying to establishing a cause. SLI is a heritable disorder and much research is underway to try and establish the genetic basis.
(12,13) SLI is of particular interest to

(12,13) SLI is of particular interest to 
researchers because of the unusual dissociation between cognitive and language ability and whether this dissociation is explained by innate modular theories of language acquisition or more general cognitive processing deﬁ  cit theories. Some attempt has been made 
to identify genetic markers of SLI such as a phonological memory deﬁ cit
(12) which stems from the research into general cognitive 
processing deﬁ  cits as underlying SLI and a speciﬁ  c tense marking 
deﬁ cit(14) or a syntax representational deﬁ  cit(15) which argues for 
the disruption of innate modular components of language.
(b)  Diagnostic overlaps between SLI and autistic spectrum 
disorders (ASD)
(i) Pragmatic language impairment
Autism and autistic spectrum disorders (ASD) are discussed exten-

sively in Chapter 9.2.2 of this text. Language and communication difficulties are central to both SLI and ASD. However, the fundamental difference between these disorders is the severity and pervasiveness of the social communication impairment. In SLI, social communication difﬁ  culties are considered secondary to the language impairment where children with speech and language 
difﬁ culties will have problems in developing appropriate social 
communication skills. In ASD, the social communication impair-
ment is an intrinsic part of the disorder and does not develop as a secondary consequence of a speech and language impairment. Due to the increase in the identiﬁ  cation of ASD and the use of the autis-
tic spectrum many more children with milder difﬁ  culties are being

tic spectrum many more children with milder difﬁ  culties are being 
diagnosed with ASD. This has led to some researchers proposing that there are overlaps between SLI and ASD.
Semantic–pragmatic disorder was ﬁ  rst described in the 1980s as 
a subtype of SLI
(16,17) and was a label used to describe children 
with comprehension problems, echolalia, behaviour difﬁ  culties, 
and difﬁ  culty with non-literal language, semantics and pragmatics. 
At the time, these children were not considered as autistic. However, the increasing use of the autistic spectrum led to debates about whether semantic–pragmatic disorder exists as a separate category of SLI or whether it should be included on the autistic spectrum.
(18,19) The crucial issue was whether the social impair-

ment was intrinsic to the language disorder or a secondary conse-quence of the language disorder. T o address this, researchers have attempted to show differences in pragmatic abilities between chil-dren with SLI, ASD, and typically developing children. For exam-ple, Bishop and Norbury
(19) identiﬁ  ed a subgroup of SLI children 
who show a proﬁ  le of Pragmatic Language Impairment (PLI). 
These children showed inappropriate behaviours across aspects of social communication including initiating conversations, under-standing subtle aspects of language such as humour and sarcasm, adapting their communication to different contexts, understand-ing and using non-verbal communication, and engaging in conver-sations about speciﬁ  c interests. Importantly, these children did not 
show the non-verbal repetitive behaviours typically characteristic of autism. Overall it is argued
(19) that there are continuities between

(19) that there are continuities between 
autism and speciﬁ  c language impairment but not all children with 
pragmatic impairments have autism. Therefore, pragmatic lan-guage impairment alone should not be used to make diagnoses of autistic spectrum disorders. It is recognized that there are conﬂ  icting opinions about the increasing evidence that indicates 
continuity between disorders that have traditionally been regarded as distinct from one another. However, assessment should consider whether a child’s social communication difﬁ  culties are being com-
pounded by language difﬁ  culties as amelioration of the language 
difﬁ culties may improve the child’s social communication.
(c)  Associations between language and behaviour in child 
Children with primary psychiatric disorders often have a history of

Children with primary psychiatric disorders often have a history of 
developmental problems which can include speech and language delay. Children with primary speech and language disorders are at greater risk of developing behaviour difﬁ  culties than children 
without speech and language disorders. Various mechanisms have been put forward to try and explain this association. These include common antecedents such as low intelligence and deprivation,
(20)
environmental factors where language stimulation is negatively affected by poor parent–child interactions or the child’s inability to attend to the language stimulus,
(21) the psychosocial rejections and 
academic failure experienced by children with communication impairments affecting their self-conﬁ  dence and self-esteem and 
therefore their subsequent emotional behaviour development,
(22–24)

(22–24)
and a neurodevelopmental abnormality or immaturity as a shared 9.2.11 children’s speech and language difficulties

SECTION 9  child and adolescent psychiatry 1714
underlying cause.(25, 26) Although the simplicity of these mecha-
nisms is appealing, identifying, and differentiating them is certainly complex.
More recently studies have shown that children with primary 
psychiatric disorders can have undetected speech and language disorders.
(27, 28) ADHD is one of the most commonly reported 
psychiatric disorders associated with speech and language difﬁ culties.
(29) In ADHD, language difﬁ  culties consist of both 
receptive and expressive problems(30) and pragmatic language dif-
ﬁ culties(31, 32) such as excessive talking and poor topic maintenance. 
Although studies have not identiﬁ  ed a distinct proﬁ  le of speech 
and language difﬁ  culties in ADHD, they should be considered in 
assessment and management.
It has been hypothesized that these undetected speech and

It has been hypothesized that these undetected speech and 
language disorders somehow play a role in the development and maintenance of the psychiatric disorder and even that the psychiat-ric disorder is secondary to the undetected speech and language disorder (see mechanisms above). There is very limited evidence available to specify what the associations are and importantly, it may be that referral practices play a role where the psychiatric problem takes priority and the child is referred to mental health services ﬁ  rst. In the United Kingdom SLT and mental health 
services are usually very separate and it is not common that SLTs work in mental health services. The identiﬁ  cation of previously 
undetected speech and language disorders in the studies above are 
really the late identiﬁ  cation of pre-existing difﬁ  culties. Nevertheless,

really the late identiﬁ  cation of pre-existing difﬁ  culties. Nevertheless, 
management of childhood psychiatric disorders should consider if speech and language difﬁ  culties are a factor in the child’s behaviour 
as they may have an impact on how the child is managed, parti-cularly with respect to participation in verbal therapies and education.
(c) Selective mutism
This childhood disorder is described as the persistent refusal to talk in certain social situations despite being able to talk in other situations. The most common pattern is talking at home but not at school and the refusal to talk cannot be better accounted for by a communication disorder or difﬁ  culties in understanding and using 
spoken language. Pervasive developmental disorder or psychotic disorder should also be excluded. The mutism must last for more than a month (this cannot be the ﬁ  rst month of school) and

spoken language. Pervasive developmental disorder or psychotic disorder should also be excluded. The mutism must last for more than a month (this cannot be the ﬁ  rst month of school) and 
interfere signiﬁ  cantly with educational progress, social communi-
cation with others, and occupational achievement. In the case of a bilingual child, it is suggested that the mutism should persist for at least 6 months and be present in both the ﬁ  rst and second language 
before diagnosis.
(33)
Selective mutism is rare and as a result only a limited number of 
studies reporting the epidemiology of this disorder are available. Prevalence ﬁ  gures estimate a prevalence of approximately 0.75 to 
0.80 per cent 
(34,35)  and it is slightly more common in girls(36) with 
an onset between the ages of 3 and 5 years.(34) Although there is

an onset between the ages of 3 and 5 years.(34) Although there is 
no clear consensus to explain the cause(s) of the disorder, social phobia, and anxiety are certainly involved. Co-morbidity with behaviour problems, communication difﬁ  culties and developmen-
tal delay are also found which indicates that a multi-factorial aetiology is the best explanation. Data regarding the long-term outcomes is scarce but there are indications that with early inter-vention improvements are made but often children are still left feeling uncomfortable in some speaking situations.(d) Intervention for selective mutism
Intervention approaches include pharmacology, cognitive behaviour therapy, family therapy, psychodynamic therapy, and speech and language therapy. Although some success with ﬂ  uox-
etine has been reported
(37) this has not been widely replicated.

(37) this has not been widely replicated. 
A behavioural approach considers the disorder as learned behav-iour and techniques including contingency management, shaping and stimulus fading, systematic desensitization, and self-modelling are advocated. Family therapy aims to identify whether there are difﬁ culties in family relationships that are contributing to the 
mutism and attempts to work with the whole family to foster more positive relationships. Psychodynamic approaches involve tech-niques of play therapy and art therapy to identify the underlying reasons for the mutism and to help the child to express the possible unconscious conﬂ  icts he is experiencing. Although children with 
selective mutism are expected to have good speech and language skills, several studies have reported a high incidence of speech and language difﬁ  culties such as articulation and expressive and recep-
tive language difﬁ  culties.
(38, 39)  In these circumstances, speech and

(38, 39)  In these circumstances, speech and 
language therapy is used as a valuable adjunct to the other approaches. Speech and language therapy aims to facilitate the child’s communication rather than resolving the underlying causes of the mutism. Therapists work with the child to desensitize him/her to communicating with others by considering the child’s communication environment and the communication load of the tasks he is expected to engage in. A hierarchy of stages is followed from easy to hard speech tasks within easy to hard speaking situa-tions. A multi-modal perspective incorporating a combination of the above approaches is advocated. The combination of family involvement with cognitive behavioural, speech and language, psy-chodynamic and family involvement meet the multi-factorial needs of this disorder. See Cohan et al.
(40) for a detailed review of the efﬁ  -

cacy of the different intervention approaches described. Although social anxiety is the predominating feature of selective mut ism, the 
resulting lack of communication is challenging. Several strategies to facilitate communication with these children are presented and these can easily be incorporated into other intervention approaches:
◆ Check that there are no speech and language difﬁ  culties that may 
be contributing to the mutism. For some children, although early 
speech and language difﬁ  culties may have resolved the child may 
still feel under conﬁ  dent in their talking.
◆ One-to-one settings are most comfortable and try and include 
the familiar person, (usually the primary carer) who the child communicates regularly with in your interventions to start with. After a while the child may be able to manage this setting with-out the familiar person. This process may have to be repeated to encourage the child to talk in another setting.

◆ Encourage and accept non-verbal communication such as head nods, writing, drawing, and gesture as well as verbal communication. Non-verbal communication is easier than talk-ing for most of these children.
◆ Follow a hierarchy of verbal communication from easy to hard, most children ﬁ  nd whispering and talking quietly easier than 
loud talking.
◆ Consider the complexity of the task the child is expected to engage in. Questions, which are factual or only require a yes or

1715
no response are much less confrontational than questions, which 
ask the child about their feelings or opinion.
Further management considerations are detailed in Johnson and 
Wintgens.(41)
Life course and outcomes
An interest in the long-term outcomes of children with speech and language difﬁ  culties has emerged fairly recently. Historically, it was 
considered that primary speech and language difﬁ  culties resolved 
over time with no implications for other areas of development. This is certainly not true and much more is now known about the developmental trajectories through childhood, adolescence, and into adult life. Generally, children with speech and language difﬁ culties continue to show difﬁ  culties not only in communica-
tion but in cognition, behaviour, educational attainment, and psychosocial functioning. This section will focus on the life course and outcomes of children with proﬁ  les of primary speech and

tion but in cognition, behaviour, educational attainment, and psychosocial functioning. This section will focus on the life course and outcomes of children with proﬁ  les of primary speech and 
language difﬁ  culties where there is no cognitive deﬁ  cit. Cognitive 
ability is a powerful predictor of development, and therefore the outcomes of children with speech and language difﬁ  culties associ-
ated with cognitive delay are usually attributed to level of IQ rather 
than the speciﬁ  c speech and language difﬁ  culties themselves.
The impact of a speech and language impairment 
over the lifespan
Speech and language impairment leads to impoverished commu-

nication skills, which certainly impact on other areas of develop-ment. The developmental trajectories of children with primary speech and language impairment show impaired receptive and expressive language development in later childhood, adolescence, and even adult life. Cognition, as measured by non-verbal IQ has been shown to ﬂ  uctuate and even deteriorate over time, particu-
larly in adolescence and later life. Research to date suggests that any deterioration is temporary and resolves but much more needs to be known about this.
(42, 43) Children with speech and language difﬁ  -

culties are more likely to experience emotional and behavioural problems (see earlier section). During the course of childhood, the risk of developing emotional and behavioural problems seems to increase with obvious negative implications for other areas of development and functioning. There is a possible association between SLD and the development of antisocial behaviour in early adult life. At the age of 19 years participants with SLD in a Canadian community sample did not show high levels of aggression but did have higher rates of arrests and convictions.
(26)
The increase in social and behaviour problems may be the result

(26)
The increase in social and behaviour problems may be the result 
of communication and interaction problems young people experience in conjunction with the increasing social and academic demands placed on them. However, it is hard to disentangle cause and effect when so many variables interact. Socio-economic status (SES), learning ability, and type of educational placement no doubt also make a contribution. Therefore, SES and IQ are probably implicated in the development of social and behavioural difﬁ  cul-
ties as well as the speech and language impairment. In adult life, severe mental health conditions such as schizophrenia, depression, and personality disorder have been linked with early histories of and persisting severe speech and language impairment.
(44)There are strong associations between speech, language, and

(44)There are strong associations between speech, language, and 
literacy development and in fact, speech and language are funda-mental in learning to read and write. In order to learn, children need to be competent communicators when they start school. Language is the medium through which children are expected to learn and literacy is dependent on identifying and discriminating speech and letter sounds. Children with persisting speech and lan-guage difﬁ  culties are at risk for literacy problems and subsequent 
low academic achievement. Children with speech and language dif-ﬁ culties ﬁ  nd it much harder to learn to read and write than chil-
dren without speech and language difﬁ  culties. Educational attain-
ment is dependent on literacy and therefore these children are very disadvantaged. Studies measuring educational attainment using Standard Assessment T ests (SAT) have found that children with speech and language difﬁ  culties gain signiﬁ  cantly lower SAT scores 
than controls.

(45) In older individuals, attainment at GCSE and 
A level is also affected. Children with speech and language difﬁ  -
culties are often bullied by their peers and can be targets for victimization.
(46) Studies suggest that this is due to their odd com-
munication particularly difﬁ  culties with social communication 
behaviour. Unclear speech is also a signiﬁ  cant factor. In adult life, 
high levels of social maladaption and poor psychosocial function-ing were found in adults in their mid 30s with SLI. Employment, relationships, independent living, and health were all signiﬁ  cantly 
and negatively affected.
(44) See Clegg(47) for a full review.
Identiﬁ  cation of children at risk
There are variations in outcomes and not all children with speech

There are variations in outcomes and not all children with speech 
and language impairment are at risk of later negative outcomes. Issues of variability and risk and resilience are not yet fully under-stood. Risk factors for poor outcomes in later life are the severity of the initial impairment, involvement of receptive language, low IQ, and low SES. Resilience factors are the presence of pure speech difﬁ culties only, high IQ, high SES, and access to specialist support. 
A critical age hypothesis
(48) proposes that any speech and language 
difﬁ culties that impact on a child’s communication after 5 years 
should be considered as signiﬁ  cant and prioritized for intervention.
Speech and language difﬁ  culties should not be underestimated

Speech and language difﬁ  culties should not be underestimated 
in terms of their impact on children’s lives. With respect to clinical management, the risk factors should be considered in identifying those children at particular risk. In the United Kingdom, there is specialist educational provision now available that provides post-16 years provision for some young adults to try and reduce negative outcomes, e.g. supporting individuals to gain further qualiﬁ  cations and to enter the work place. Information about long-
term outcomes can certainly inform the individuals themselves, their families, and other professionals about prognoses and how best to support individuals to meet their learning and other needs effectively.

Speech and language therapists (SLTs) work in education, health, and social care, voluntary organizations and independent practice. A SLT is an important member of the interdisciplinary team and will lead on the assessment, differential diagnosis, intervention with, and management of individuals with communication and swallowing disorders. In recent years due to the shift to inclusion, many paediatric SLTs now work in schools with educational 9.2.11 children’s speech and language difficulties

SECTION 9  child and adolescent psychiatry 1716
professionals as part of the school team. This enables the SLT to 
contribute to statements of special education needs, formulating independent learning plans (ILP), and delivering the curriculum to make it accessible for children with speech and language difﬁ  cul-
ties. SLTs also work in community services such as the government Sure Start programme, primary and secondary health care, e.g. acute hospital settings and community clinics, specialist health services, e.g. child development centres and education, e.g. from preschool, mainstream and special schools/resourced provision. The inclusion of SLTs in Child and Adolescent Mental Health Services (CAMHS) is increasing but this is not consistent across the United Kingdom. However, there is now recognition that the SLT can have a valuable role within the CAMHS
(49,50) in terms of the 
identiﬁ  cation of any communication difﬁ  culties and the subse-

quent impact on mental health and offering intervention that will help to ameliorate the communication difﬁ  culty and facilitate 
communication. Within CAMHS, a SLT may be employed in a spe-cialist unit, child psychiatry outpatient service, or other. Differential diagnoses are usually made in collaboration with the team and a SLT will use a combination of formal and informal assessment. Formal assessment consists of using measures that compare the child’s speech and language abilities with abilities that are expected for the child’s chronological age. Various types of assessments are available criterion referenced, standardized, developmental scales, and observational. Intervention may be direct, i.e. individual or as part of a group or indirect, i.e. through working with the family or in the context of the child’s classroom and school.
Identiﬁ  cation of speech and language difﬁ  culties

Identiﬁ  cation of speech and language difﬁ  culties 
in children
The following checklist may be helpful when working with young 
school age children in identifying speech and language difﬁ  culties 
and initiating referral to speech and language therapy services.
(a) Speech
1 Is the child’s speech difﬁ  cult to understand?
2 Does the child miss out sounds from words?3 Is the child less intelligible when speaking in sentences than in single words?If yes , to one or more of the above then speech difﬁ  culties are 
evident and referral to speech and language therapy is advised.
(b) Comprehension
1 Can the child follow and engage in conversations with both chil-dren and adults?2 Can the child carry out verbal instructions correctly or does he need lots of prompting?3 Can the child understand a range of concepts such as time and space?If no , to one or more of the above then comprehension difﬁ  culties 
are evident and referral to speech and language therapy is advised.
(c) Production

1 Does the child have a wide range of vocabulary?2 Can the child use more complex sentences such as the ‘the boy 
ran for the bus because he was late’ rather than the boy was late and 
ran for the bus?
3 Is the child able to give a narrative of a past and future event?4 Does the child frequently say non-speciﬁ  c words such as ‘stuff’ 
or ‘thingy’ or hesitate when talking?If no  to 1 to 3 and yes to 4 then production difficulties are 
(d) Social communication
1 Is the child willing to participate in conversations and does he enjoy this?2 When the child talks, is it meaningful and relevant to the conversation and/or situation?3 Does the child use appropriate verbal and non-verbal communication behaviours?If no  to one or more of the above the social communication difﬁ  -

culties are evident and referral to speech and language therapy is advised.
(e) Education and social activities
1 How is the child functioning at school?2 Is the child able to access and participate in a range of social activities?3 Are the speech and language difﬁ  culties long standing and 
persisting beyond the age of 5 years?If the child is struggling to meet the demands of school and pres-ents with persisting speech and language difﬁ  culties then this is a 
cause of concern for later development and outcomes. Referral to speech and language therapy is advised.
General principles for working with children with 
speech and language difﬁ  culties
It may be useful to consider these general principles when working 
with children with speech and language difﬁ  culties
1 Consider your own communication and adapt it to:
◆ Offer forced choice answers.
◆ Break up long instructions and sentences into short steps.
◆ Slowdown delivery and use pauses.

◆ Use short simple sentences with familiar vocabulary and avoid 
ambiguous language.
◆ Use visual strategies such as pictures, real objects, and symbols to support spoken language.
◆ Remember that children with spoken speech and language difﬁ culties will also have written language difﬁ  culties.
2 It is always challenging when you are unable to understand what 
a child is saying to you. While there is no perfect solution, the following strategies will help:
◆ Reassure the child that you are interested in what they are trying to tell you.
◆ Be honest and say that you don’t understand but also make it clear which parts you did and did not understand.
◆ Offer a choice of possible answers to the child, as this will reduce the number of choices available to you to guess from.

◆ Ask the child to show you something to help or can the child describe it to you or point to it or draw it.
◆ If these are still not successful, reassure the child that you are interested in what they are trying to tell you and that you will try again later.

1717
Speake, J. (2004). How to identify and support children with speech and 
language difﬁ  culties . LDA, Cambridge, UK.
This is a useful text, which describes children’s speech and language 
difﬁ culties and offers practical strategies for assessment and 
management.
www.afasic.org.uk
Afasic is a UK charity that offers information and advice to children 
with speech and language difﬁ  culties and their families as well as 
professionals working in this area.
www.ican.org.uk
ICAN is a UK charity that funds specialist educational provision for 
children and adolescents with severe speech and language difﬁ  culties as 
well as offering information and advice.
www.rcslt.orgThe Royal College of Speech and Language Therapists (RCSLT) is the 
professional body for practicing speech and language therapists in the UK. Information about speech and language therapy services is available on this website.

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50–5.9.2.12 Gender identity disorder 
in children and adolescents
Variance in psychosexual development
Psychosexual development of sex-typed behaviours spans a broad 
mix of the elements that comprise ‘masculinity’ and ‘femininity’ . The possibility for variation is extensive. Among males, there are boys and men whose stereotypical masculinity may pose problems in mental health and criminality. They are not the focus here. Rather, here it is the marked deviation from the mean towards the ‘non-masculine’ or ‘feminine’ extreme. That pattern can also cause clinical concern and constitutes gender identity disorder ( GID ) as

manifested in childhood. For females, conventional ‘tomboyism’ is not the focus here, but rather the extreme that can cause clinical concern and constitutes GID.
No epidemiological studies exist of GID in children. Prevalence can be estimated only roughly from indirect sources. Two items on the Child Behaviour Checklist
(1) are consistent with components of 
the diagnosis. They are ‘behaves like opposite sex’ and ‘wishes to be of opposite sex’ . Among 4- to 5-year old boys, not clinically referred for behavioural problems, about 1 per cent of parents answer in the afﬁ rmative that their child ‘wishes to be the opposite sex’ . For ages 6

to 7 it drops to near zero, but rises to 2 per cent at age 11. For girls, the highest rate was 5 per cent at ages 4 to 5, but less than 3 per cent for other ages. With respect to ‘behaves like opposite sex’ , among the boys the rate was 5 per cent and among girls 11 per cent for all ages. However, these data do not indicate any longitudinal aspect of the reported behaviour, and do not detail the behaviour.
(2)
An alternative source of estimation looks to the percentage of 
adults believed to be homosexually oriented. From this population the percentage of homosexual men and women who typically report childhood cross-gender behaviour is used for the estimate. If the rate of exclusive homosexuality is 3 to 4 per cent for men and 1.5 to 2 per cent for women,
(3) with perhaps half of homosexual 
men and women recalling childhood cross-gender behaviour,(4,5)

the estimate of childhood cross-gender behaviour is about 3 per cent for boys and under 1 per cent for girls. However, this estimate suffers from problems of retrospective recall and poor comparabil-ity between surveys of adults. Further, the recalled behaviour may not have constituted GID.
A disparate sex ratio is evident in referral rates with GID. Four to 
ﬁ ve boys to one girl are referred. One reason may be greater parental 
concern over cross-gender behaviour in boys and the greater stigmatizing peer group response to ‘sissiness’ than to ‘tomboyism’ . An alternative explanation is that, as with most atypical patterns of sexuality, there is a higher ratio of males to females reﬂ  ecting 
a common intrinsic predisposition among males.
Children with GID differ from other children, including those who merely are not conventionally masculine or feminine as boys or

1719
girls. Their behaviours are typical of other-sex children. Not only 
do they express a wish to be the other sex, at least in earlier years before they may learn not to verbalize it, but also their dressing preferences, peer group preferences, toy preferences, game prefer-ences, and perhaps their physical mannerisms are those of the other sex.
(6)
The picture of GID in children as described in DSM-IVTR,(7)
can manifest, in part, by the repeatedly stated desire to be of the other sex: in boys by a preference for dressing in girls’ or women’s clothing or simulating female attire from available materials, and in girls an insistence on wearing stereotypically masculine clothing with refusal to wear traditional girls’ clothing. In role playing, as in make-believe play or imitating media characters, there is a strong preference by the child for other-sex roles. There is also a strong preference for toys generally identiﬁ  ed with the other sex, such as

Barbie dolls by boys. The peer group is composed primarily or exclusively of other-sex children. Pictures drawn are generally of other-sex ﬁ  gures. There may be cross-sex physical mannerisms. 
Concurrently, there is an avoidance of traditionally sex-typed activities. Criteria in ICD-10 are similar.
(8)
The diagnosis of GID in girls can be more problematic than in 
boys. This is because ‘tomboyism’ is a more common part of paedi-atric psychosexual development than ‘sissyness’ . There is, however, a distinction between GID in girls and tomboyism. Typical tomboys do not insist that they want to be boys and will wear girls’ clothes from time to time, will have both girls and boys as playmates, and will not work to present themselves as young boys.
Substantial cross-gender behaviours are generally manifest in

Substantial cross-gender behaviours are generally manifest in 
the third or fourth year. Although they are believed by parents and perhaps professional advisors to be a passing phase, at least with those children, seen clinically they endure into school years. Most children are evaluated at about age 7 or 8, when parents become increasingly concerned that the ‘passing phase’ is not passing and negative reactions by the peer group are enhanced, causing the 
child social distress.
(6)
Aetiology
Understanding the aetiology of GID considers typical inﬂ  uences 
on early psychosexual development in male and female children.
Early sex differences

(6)
Aetiology
Very early behavioural differences are evident between males and females. There may be recognition of the ‘like me’ , ‘not like me’ dichotomy of one’s sex. When boys and girls aged between 10 and 18 months were shown pictures of faces of infants of the same and other-sex, males looked at faces of males longer and females looked at faces of females longer. This ‘like me’ , ‘not like me’ dichotomy is also interpretable in the study in which two male and two female 1-year-old children were placed at the four corners of a room and permitted, one at a time, to crawl to any other child. Children more often crawled to a child of the same sex.
(9,10)
In early play patterns, boys and girls may differ. When 12-month-

(9,10)
old children were observed with their fathers in a waiting room, boys were more likely to handle ‘forbidden’ objects such as trays and vases.
(11) The 1-year-old’s toy preferences may also differ, with 
girls preferring soft toys and dolls and boys preferring transporta-tion toys and robots.
(12,13)
Preference for mother or father appears to discriminate boys and 
girls early. When 2- to 3-year-old children were asked which parent in an adjoining room they would prefer to play a game with, or to 
build with using blocks, or make a sketch with, both boys and girls preferred their father. At 4 years, girls shifted to mother but boys stayed with father.
(14)
When children aged between 2 and 3 years were observed in

(14)
When children aged between 2 and 3 years were observed in 
a free play setting, boys were more aggressive toward peers and showed more rough-and-tumble play. When paired in a test play situation with a boy, girls showed more passive behaviour, i.e. standing or sitting quietly and watching their partner play.
(15)
The preference for a same-sex peer group emerges early. When 
3.5- to 4.5-year-olds were shown pairs of photographs of boys and girls and asked to select the children with whom they would prefer playing, boys preferred boys and girls preferred girls.
(16)
Children become aware of sex role stereotypes early. At 2 years of 
age, boys believe that boys like to play with cars and help their father, 3-year-olds believe that boys like to build things and that only boys like to play with trains. They also believe that girls like to play with dolls, help mother, and cook dinner. Girls are also seen as more likely to say ‘I need help’ .
(17)

(17)
The peer group inﬂ  uences psychosexual development. In mixed-
gender peer groups, boys more often receive positive responses for masculine activities than girls receive for feminine activities. Boys seem more responsive to peer pressure, in that they will discontinue feminine activities more rapidly than girls will discon-tinue masculine activities when they are the target of negative responses from either boys or girls.
(18)
These ﬁ  ndings suggest that if sex-typed attributes emerge in 
psychosexual development of typical children shortly after the basic dichotomization of ‘like me’ , ‘not like me’ , or male/female, then the ﬁ  rst two components of gender identity are consolidated 
early: (a) the basic sense of male or female; (b) masculine or femi nine 
gender role. The age at which they consolidate coincides with the emergence of signiﬁ  cant cross-gender identity and behaviour 
as seen in the GID of childhood.

Fathers, when observed with 12-month-old children, were more 
likely to present their sons with trucks rather than dolls, whereas daughters were given both trucks and dolls equally. However, among those children who were given dolls, boys played with them less.
(19)
Mothers of young children have been observed with infant actor/
actress babies (Baby X experiments). Some of these stranger infants are cross-dressed or given cross-sex names. The perceived sex of the infant inﬂ  uences the mother’s behaviour. Children believed 
to be boys, whether they were or not, were more likely to be encour-aged to physical action. Infants believed to be girls were more likely to be given a doll, whereas male infants were more likely to be presented with a football.
(20)

(20)
None of these ﬁ  ndings of early sex differences have been system-
atically observed with children followed up years later to determine whether early variation from the more common patterns are associated with later variation in psychosexual development.
In our prospective research of several dozen cross-gender behav-
ing boys and conventionally masculine boys,
(21) more mother-son 
shared time was not found in the group of feminine (prehomo-sexual) versus masculine boys. There was substantial variability in the extent to which mothers and sons were emotionally close. However, with respect to father-son experiences, feminine boys 9.2.12 gender identity disorder in children and adolescents

SECTION 9  child and adolescent psychiatry 1720
shared less time with their fathers in their ﬁ  rst years when com-
pared with the contrast group of conventionally masculine boys or with their masculine preheterosexual brothers. There was an inverse relationship between the extent of father-son shared time in the ﬁ rst years and later Kinsey score of sexual orientation. Less father-
son time was associated with a higher (more homosexual) score.
Identifying the ‘chicken and egg’ here is problematic. Possibly, 
boys with a feminine identiﬁ  cation who prefer feminine-type 
activities are less interesting to their fathers. This would lead to father-son distancing. In many of the families, this was the case. However, the ﬁ  nding that early father absence or father-son aliena-
tion was associated with cross-gender behaviour was not invariable. Further, there are families in which the mother and father relate comfortably with children and in which GID manifests itself.
Hormonal inﬂ  uences

Evidence for hormonal inﬂ  uences on psychosexual development 
derives primarily from studies of the intersexed. Girls with congenital virilizing adrenal hyperplasia who produce an excess of androgen beginning prenatally are more rough-and-tumble in childhood play behaviours and less interested in doll play. They are more likely to be considered tomboys.
(22) However, less evidence 
exists for a deﬁ  ciency in prenatal androgen for boys with cross-
gender behaviours.(23–25) Prenatal sex hormone levels are impor-
tant theoretically, in that to the extent they inﬂ  uence sex-typed 
behaviour, such as rough-and-tumble or doll play, they may inﬂ  u-
ence peer group composition. They may inﬂ  uence the labelling 
of the child as ‘sissy’ or ‘tomboy’ , and may place the child on an atypical developmental track.
Seminal studies of the intersexed in the 1950s indicated that the 
sex of assignment in the ﬁ  rst 2 to 3 years of life was the critical

sex of assignment in the ﬁ  rst 2 to 3 years of life was the critical 
variable in establishing the basic concept of sexual identity as male or female. This was irrespective of gonadal status, hormonal status, internal reproductive structures, and, to some extent, genital con-ﬁ guration.
(26)These studies have been criticized on the ground that 
with the anatomically intersexed the prenatal endocrine status has not been normal.
(27) Thus recent interest has focused on 
individuals believed to have had normal prenatal development but who shortly after birth were nevertheless reassigned to live in the other-sex role, as well as those with a prenatal abnormality.
In one widely publicized case, one male of a pair of monozygotic 
twins suffered penectomy through circumcision trauma in the ﬁ  rst

twins suffered penectomy through circumcision trauma in the ﬁ  rst 
year of life and was reassigned to live as a girl alongside the boy co-twin at about 23 months of age. Although earlier reports indi-cated that the reassigned twin was adjusting successfully to life as a girl,
(28) more recent follow-up revealed that the individual reverted 
to living as a male in late adolescence, had undergone phalloplasty, and married a female.
(29) The other case involves a male infant 
who also underwent penectomy from circumcision trauma and was assigned to live as a girl, earlier, in the seventh month. That individual was reported to be living as a woman and is bisexual in orientation.
(30) One explanation for the discrepancy in the two 
reports is that the ﬁ  rst child was reassigned as a female later than

reports is that the ﬁ  rst child was reassigned as a female later than 
the time during which basic identity of male or female may be set. Both reports, however, suggest a prenatal inﬂ  uence on sexual 
orientation.
Children born with cloacal exstrophy also provide evidence 
for prenatal factors inﬂ  uencing gender identity, irrespective of 
postnatal socialization. Prenatal sex steroid levels are thought to be normal. However, the genital area of these infants, if chromosoma-
lly male is so malformed, that there is little prospect of male genital reconstruction. Therefore, many are socialized as girls. Reports from the US reveal a high rate of rejection of living as girls and transition to living as boys.
 (31) However, an early report from the 
UK does not indicate female gender role rejection.(32)
The enzyme deﬁ  ciency of 5-alpha reductase is another clinical 
example of competing inﬂ  uences of prenatal sex steroids and

example of competing inﬂ  uences of prenatal sex steroids and 
postnatal socialization. Without this enzyme testosterone is not converted to dihydrotestosterone, needed prenatally to virilize the genitalia. At birth these chromosomal males with intra-abdominal testes appear to be girls based on their external genitalia. Traditionally, they have been raised as girls. Then, at puberty, they do not feminize but rather their clitoris grows substantially to resemble a phallus and there is no gynecomastia. Most then adopt a male role.
(33) Debate continues whether this facility to live 
as heterosexual men is the product of prenatal testosterone or the extensive body virilization and social pressures to live as men. Long-term study of children where the testes are removed before puberty will provide further information.
Longitudinal aspects of atypical early 

Beginning in the late 1960s, the author conducted a prospective 
study of several dozen boys with extensive cross-gender identiﬁ  cation 
and behaviour.(6) Most of these boys would today be diagnosed 
with GID, although at the time the diagnosis had not yet entered into the diagnostic nomenclature. These boys were evaluated peri-odically and assessments continued until late adolescence or young adulthood for two-thirds. At that time, three-quarters of the boys were homosexual or bisexual. One was gender dysphoric. In con-trast, a demographically matched group of boys with conventional boyhood behaviours was heterosexual at outcome.
(34)More recent 
follow-up studies at another program reveal a higher minority percentage of cross-gender children remaining gender dysphoric but with the majority homosexually oriented.
(35)
These prospective studies are consistent with retrospective

(35)
These prospective studies are consistent with retrospective 
reports by adult transsexual males and homosexual males. Many transsexuals recall extensive cross-gender identiﬁ  cation and behav-
iours in childhood. Often, however, these are not documentable because of the length of time from onset to description and the dif-ﬁ culty of corroboration. Several studies have interviewed adult gay 
men and lesbian women with respect to gender-typed behaviours in childhood. Typically, more extensive cross-gender behaviours are reported than by groups of heterosexual men and women. These retrospective studies of men and women are consistent cross-culturally.
(4, 5)
Of theoretical and practical import is the overlap in childhood

(4, 5)
Of theoretical and practical import is the overlap in childhood 
gender behaviours between retrospective reports given by trans-sexuals and homosexuals, and in the prospective study of cross-gendered boys. Because transsexualism and homosexuality in the adult male are quite different, the question is: Why should there be such an overlap?
One possibility is that the two groups are relatively similar in 
earlier years, but that different life circumstances promote more comfort for one group continuing to live as males. Treatment intervention to change cross-gender behaviour may be decisive. Transsexuals were rarely treated as children. Different prevalence

1721
rates may also be key. Whereas the incidence of transsexualism may 
be one in 10 000 males,(36) the incidence of homosexuality may be 
3 or 4 per cent.(3) Thus if there are overlapping behaviours between 
the two in early years, probability would predict that the vast majority of cross-gendered males will emerge as homosexual, rather than transsexual. However, this does not explain the behav-ioural overlap between prehomosexual boys and pre-transsexual boys who will later be sexually attracted only to females (the latter living as lesbian women after sex reassignment surgery).
Gender identity and mental disorder

GID of childhood was introduced into the DSM in 1980. Its inclu-sion derived from the prospective study of cross-gender behaving boys described above, with the present author also being a member of the nomenclature committee. The criteria for a set of behaviours being included in the DSM was that a condition be experienced subjectively as distressing and that it constitute a social disadvantage. GID of childhood met the criteria because of the distress the chil-dren experienced in consequence of being either male or female and the peer group stigmatization that ﬂ  owed from their behaviours.
In the past decade, there has been increasing controversy over 
whether GID of childhood should remain in the list of disorders. In the same period in which GID of childhood was introduced, homosexuality was removed. As our prospective study revealed that a substantial majority of boys with GID matured into homo-

sexual men, to some critics the inclusion of GID was seen as a back-
door through which homosexuality reentered the list of disorders. A response to this concern is that when the subjective distress of being male or female present in children with GID disappears the person no longer has a disorder, whether a heterosexual or homosexual adult. On the other hand, when the distress of being male or female persists, the diagnosis remains GID as seen in ado-lescence or adulthood, commonly termed transsexualism.
Inclusion of GID for children in the list of disorders is also seen 
by some critics as perpetuating sex stereotyping in society, and demanding that children conform to traditional masculine/feminine behaviours. A response to this is that the diagnosis is not made merely for gender non-conformity but only when the child is unhappy being male or female, and where the child’s behaviours are so atypical that there is substantial adverse reaction from the peer group.
Initial assessment

In the initial assessment of children with suspected GID, the pro-fessional should attempt to engage both parents as well as the child. Frequently there is reluctance by one parent, usually the father, to attend. However, this is a family matter, and the clinician needs to gain impressions of the parent-child relationship, the parent-parent relationship, and the child’s behaviour from both parents as well as the child.
Assessment is directed towards understanding whether the 
behaviours described represent a normal variant of psychosexual development. Does the child overtly express dissatisfaction being the sex to which he or she was born? Is there a marked skewing of gender-typed behaviours towards those of other-sexed children or is there some mix? How long has there been cross-gender behaviour? What have parental reactions been to it initially and more recently? What is the child’s response when parents attempt

to frustrate the cross-gender toy or clothing preferences, if such attempts have been made? What time availability is there for each parent with the child? What do they do together? Are there other persons, for example grandparents or teachers, who may be rein-forcing cross-gender behaviours? What are the parental concerns, both in the short and long term, with respect to the signiﬁ  cance of 
the behaviours? Are there other behavioural or medical problems in addition to the gender identity issue?
Treatment
Typically, three principal targets are set for intervention with GID in children. First, the children are unhappy being the sex to which they were born; second, they are experiencing substantial peer group alienation; third, there is conﬂ  ict with one or both parents in

consequence of their atypical behaviour. A principal intervention strategy is helping the child understand that the world of gender is not necessarily black and white, but that greys exist as well. Boys can understand that not all boys need to be good athletes or rough-and-tumblers, and that boys can be sensitive and creative. Girls do not have to be boys to participate in rough-and-tumble play and sports. Children do not need to conform arbitrarily to all sex-typed attributes to remain in their birth sex role. T o the extent this can be internalized, the path to transsexualism may be blocked.
The peer group of children with GID can be expanded to include 
children of both sexes. Parents may have to make efforts, particu-
larly with cross-gendered boys, to ﬁ  nd boys of their son’s age who

larly with cross-gendered boys, to ﬁ  nd boys of their son’s age who 
will enjoy non-athletic non-rough-and-tumble companionship, perhaps engaging in board games or computer games together. Similarly, girls with GID who are very athletically motivated may ﬁ nd girls who are also athletically inclined, and not just boys 
to play with. Children who develop comfort in socializing with both boys and girls may experience enhancement of same-sex identiﬁ  cation.
Cross-gendered boys are notably alienated from their fathers and 
intervention can promote their relationship by ﬁ  nding mutually 
enjoyable activities. This may serve as a source of same-sex identiﬁ  -
cation in the child, will enhance the quality of the parent-child relationship, and will be a positive outcome irrespective of its inﬂ uence on later sexual identity.
Very few adult transsexuals had entered into any treatment

Very few adult transsexuals had entered into any treatment 
intervention to address GID during childhood. Children with GID referred for evaluation or treatment may, as a product of that concern by parents, and/or professional intervention, have that route to transsexualism diverted. However, there is no empirical support for intervention directed at emerging sexual orientation. There is no evidence that a speciﬁ  c type of ‘treatment’ in childhood 
has any effect on outcome on that dimension of gender identity.
(34)
Parents should understand that if they are concerned about the ultimate sexual orientation of their child, that is a long time ahead. For the immediate period the child is unhappy who he or she is, is experiencing conﬂ  ict with the peer group, and may be having dif-
ficulties at home with at least one parent. These are concerns that should be addressed.
Cross-gender living by children

In recent years, some children with GID have been permitted to live as children of the other sex. Their parents consider that the 9.2.12 gender identity disorder in children and adolescents

SECTION 9  child and adolescent psychiatry 1722
strong preference by their child for the dress, activities, and com-
panionship of the other sex with aversion to conventional sex-typed activities, along with the stated preference for being the other sex, argues for the child expressing its gender needs. Complexities of this decision include integrating it into the child’s school and neighborhood environment.
Typically, children with GID experience peer group stigma and 
domestic conﬂ  ict in consequence of their gender identity. Reduction 
of conﬂ  icts could enhance self-esteem. This social experiment 
should provide information on whether the longer-term status of the children differs from the children with GID not permitted cross-gender living, most of whom mature into homosexual adults and a minority into transsexual adults.
Early adolescent gender identity disorder

GID continuing into adolescence merges with GID of adulthood. Management issues address the young teenager’s continuing gen-der dysphoria and the consequent social problems. There may be peer group alienation. Depression may develop. School avoidance may develop. Awareness of sexual attraction to same-sex persons may be an additional source of conﬂ  ict. Parents may be unaware of 
their teen’s GID.
GID in adolescents presents medical, legal, and ethical dilemmas 
for clinicians. The somatic changes of puberty are very distressing to these young teenagers. And for those who will ultimately progress to adult GID or transsexualism, these changes may pose substantial obstacles to effective ‘passing’ in their desired gender role. The latter is especially true for males as the voice deepens, facial hair sprouts, and skeletal proportions masculinize. For females, menses are espe-
cially troublesome, though not visible, and breast development,

cially troublesome, though not visible, and breast development, 
especially when prominent, is very distressing.
Clinical recognition of these issues has led to an innovative 
program for some young teens with GID. This is a trial period of putting puberty on hold and possibly a later cross-sex hormone induced puberty. In the Netherlands, treatment may consist of administering a gonadotrophin releasing hormone agonist (GnRH analogue) at Tanner Stage 2-3 to block secretion of sex steroids that promote pubertal changes. This could be at age 12–14. Depending on the clinical picture of gender identity, at age 16, cross-sex ster-oids may be administered, or the analogue withdrawn so that endogenous puberty continues.
(37) UK practice disfavors analogue

(37) UK practice disfavors analogue 
treatment prior to Tanner Stage 4 or 5 after substantial pubertal changes. In the early experience of the Dutch treatment program, no patients who have commenced hormonal treatments prior to age 18 have regretted the decision to live as a person of the other sex. Although there is concern that a couple of years of gonadal steroid suppression could predispose to osteoporosis, this concern remains theoretical.
Legally, there is no age barrier to a minor consenting to a medical 
intervention in the United Kingdom, providing that there is sufﬁ cient understanding of the implications of the treatment.
(38)
At 16 years, adolescents are presumed competent to consent to 
medical treatment..
The psychiatric management dilemma here is predicting which 
gender dysphoric adolescents will mature into adult transsexuals, and which will be able to live in the gender role expected from 
birth, perhaps as homosexual adult men and women.Further information

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AC 112.9.2.12 gender identity disorder in children and adolescents

Contents
and the environment
 9.3.2 Child trauma
 9.3.3 Child abuse and neglect
 9.3.4 The relationship between physical and mental health in children and adolescents
 9.3.5 The effects on child and adult mental health of adoption and foster care
 9.3.6 Effects of parental psychiatric and physcial illness on child development
Paul Ramchandani, Alan Stein, and Lynne Murray
 9.3.7 The effects of bereavement in childhood
9.3.1 The inﬂ  uence of family, 
school, and the environment
Barbara Maughan 
Like adult disorders, most child psychiatric problems are now

Like adult disorders, most child psychiatric problems are now 
regarded as multifactorially determined: both genetic and environ-mental factors play a role in their development. This chapter provides an overview of some of the key environmental elements in that equation. Subsequent chapters discuss risks for speciﬁ  c dis-
orders; the focus here is on the more general issues that arise when 9.3
Situations affecting 
child mental health
considering the effect of environmental inﬂ  uences on the onset or 
persistence of psychopathology in childhood.
Environments and development

As in all aspects of child psychiatry, a developmental perspective is crucial when considering environmental risks. Some developmental periods may be especially sensitive for neurodevelopment, and show heightened effects of environmental insults. In addition, key sources of environmental inﬂ  uence change with age, and the 
meaning and impact of events will vary with the child’s stage of cognitive, emotional, and social development. The family is the central source of early environmental inﬂ  uences, charged as it is in

most societies with prime responsibility for the care, nurture, and socialization of the young. As children develop, so their social worlds expand; childcare and school settings take on increased importance, as do relationships with friends and peers. Throughout, each of these proximal contexts is shaped by inﬂ  uences from the 
wider culture and society. Any comprehensive assessment of 
a child’s environment needs to take each of these types and levels 
of inﬂ  uence into account.
Nature-nurture interplay
At one time, causal associations between adverse experiences and 
childhood disorder were assumed to run in just one direction. T oday, it is clear that the situation is vastly more complex. Children 
are not simply passive recipients of experience; they inﬂ  uence, as 
well as being inﬂ  uenced by, those around them, and they play an 
active role in constructing and interpreting their social worlds.
(1)
Even very young infants inﬂ  uence the nature of their interactions

(1)
Even very young infants inﬂ  uence the nature of their interactions 
with caregivers, and children’s capacities for shaping and selecting their experiences increase as they mature. The temperamentally difﬁ cult child is likely to evoke more negative responses from par-
ents; when parents themselves are under stress, or ﬁ  nd it hard to 
maintain consistency, troublesome child behaviours can play a key role in fuelling harsh or punitive responses. Delinquent adolescents may seek out delinquent peers, who further encourage their antiso-cial activities. Associations between environmental factors and dis-order often involve complex reciprocal patterns of effects.
Some of the evocative effects of children’s behaviour will reﬂ  ect 
heritable traits.
(2) The advent of behaviour–genetic studies in child 
psychiatry has provided important insights into environmental as

1725
well as genetic risks. Genetic analyses have shown, for example, that 
many ostensibly ‘environmental’ factors include some element of genetic mediation.
(3) Parents provide children not only with their 
environments but also with their genes, so that in biologically relat-
ed families, nature and nurture are inevitably interwoven. Musical parents will encourage their children to enjoy music, buy them a violin, and may also pass on musical talents. In a similar way, anti-social parents may rear children in hostile and punitive environ-ments, provide models of antisocial behaviour, and also pass on genes that predispose to disruptive behaviours. In all likelihood, genes and environments will often be correlated  in this way.
Genetically informative studies have also highlighted other key 
mechanisms in gene-environment interplay .
(4) First, environments 
may moderate  genetic inﬂ  uences, such that the heritability of some

may moderate  genetic inﬂ  uences, such that the heritability of some 
traits may vary systematically with qualities of the environment. Second, genetic factors may contribute to differential sensitivity to 
environmental risks . Research has consistently shown marked indi-
vidual differences in children’s responses to all but the most severe forms of psychosocial adversity. As yet, reasons for these differences are not well understood. They may reﬂ  ect variations in the severity 
of exposure; individual differences in resilience or coping strate-gies, or in environmental sources of protection; or variations in vulnerability. Genetic predispositions clearly constitute one source of such vulnerability, and several examples of gene x environment interactions have now been documented. Finally, pre-clinical studies provide clear evidence that environments can inﬂ  uence

gene expression  through epigenesis;  as yet, the extent to which proc-
esses of this kind apply in humans is unknown.
Risk variables and risk mechanisms
Identifying environmental factors that show links with children’s 
adjustment is only the first step in understanding how they 
function to increase risk for disorder. A variety of different mecha-nisms has been proposed here. Some may run through the effects of stress on the biological substrate. Exposure to aggression and hostility may inﬂ  uence children’s cognitive processing, leading to 
the development of negative cognitive sets and attributional biases. In a related way, disrupted early attachments are argued to affect the psychological structures needed for later relationship formation. Adverse experiences may lead to direct increases in negative emo-tionality, disruptive behaviours, and impulsiveness, or to negative interactional styles that impact on social relationships. And ﬁ  nally,

stress may affect children’s self-concepts, or compromise their coping skills in ways that increase the risks for disorder. Any given environmental risk may be associated with a number of risk mech-
anisms, and the processes involved in the persistence of disorder 
may differ from those involved in its onset.
Family inﬂ  uences
Pre- and early post-natal development
Some vulnerability to psychopathology is laid down in foetal 
development. The potential for adverse effects of maternal sub-
stance use on the developing foetus have been known for many 
years; much recent attention has focussed on associations between 
prenatal cigarette smoking and risk for externalizing disorders in 
offspring. In addition, current estimates suggest that as much as 15 per cent of the load of childhood emotional/behavioural prob-lems may be attributable to exposure to maternal anxiety and stress in pregnancy. Though the mechanisms involved here remain to be

elucidated, there is speculation that these effects may reﬂ  ect foetal 
programming of stress response systems akin to those posited in studies of early life inﬂ  uences on risk for cardiovascular disease.
Post-natally, as children progress from the complete dependence 
of infancy to increasing independence, they need stable and secure family relationships to provide emotional warmth, responsiveness, and constructive discipline. The inﬂ  uential work of Bowlby
(5) and 
others has shown that a child’s need to be attached to others is a basic part of our biological heritage. Infants become increasingly socially responsive over the ﬁ  rst 6 months of life. At 6 to 8 months 
of age they begin to form selective attachments to particular indi-viduals; they seek proximity to these attachment ﬁ  gures if distressed

of age they begin to form selective attachments to particular indi-viduals; they seek proximity to these attachment ﬁ  gures if distressed 
or frightened, and protest if the person they are attached to leaves. In evolutionary terms, these behaviours function to provide pro-tection for the infant, and to reduce anxiety and distress.
Almost all infants—even those neglected or maltreated by their 
carers—develop attachment relationships of this kind. Their qual-ity varies, however, depending on characteristics of the parent, the child, and the mesh between the two. Infants who have received sensitive and responsive care tend to show secure  attachment 
patterns; insecure  attachments are more likely to develop when 
parents themselves are stressed or unsupported, and are unrespon-
sive to their children. Two main types of insecure attachment have been identiﬁ  ed: avoidant attachments (associated with rejecting or

sive to their children. Two main types of insecure attachment have been identiﬁ  ed: avoidant attachments (associated with rejecting or 
highly intrusive parental care) and resistant–ambivalent patterns (associated with inconsistent or unresponsive parenting). More recently, a third disorganized category has been described, in which infants show a variety of contradictory behaviours after brief separations, and often appear confused, depressed, or apprehensive. This seems especially associated with parental behaviours that are frightening, unpredictable, or abusive.
Attachment theorists argue that the quality of these early rela-
tionships may have long-term implications. Though not entirely resistant to change, infants’ attachment patterns do tend to be stable over time. Some of this stability may reﬂ  ect continuity in the

tionships may have long-term implications. Though not entirely resistant to change, infants’ attachment patterns do tend to be stable over time. Some of this stability may reﬂ  ect continuity in the 
quality of family care. In addition, attachment theory proposes that early attachment experiences are internalized in internal working models of self and others, which function as templates for future relationship formation. Children who have experienced responsive early care come to expect others to be caring and reliable; those who have been ignored or rejected develop less positive expectan-cies of others, of relationships, and of themselves. Later in development, new relationships may be created in line with these expectancies.
Although many aspects of these models await conﬁ  rmation, 
securely attached infants are known to go on to be more sociable and co-operative in their social relationships, and to show more positive affect and self-esteem. Insecurely attached infants show

securely attached infants are known to go on to be more sociable and co-operative in their social relationships, and to show more positive affect and self-esteem. Insecurely attached infants show 
less positive relationships, and are at some increased risk for psy-
chopathology. Taken alone, attachment security in infancy is only a weak predictor of global functioning in early adulthood, suggesting that early attachment experiences work with and through other experiences—including peer relationships, later family experiences, and eventually mature intimate relationships—to contribute to later functioning. In addition, both ICD-10 and DSM-IV recognize two varieties of attachment disorders: non-attachment with emo-tional withdrawal, typically associated with abuse, and non-attach-ment with indiscriminate sociability, most usually observed when 9.3.1 the influence of family, school, and the environment

SECTION 9  child and adolescent psychiatry 1726
children have been exposed to repeated changes of caretaker or 
institutional care. Although as many as 40 per cent of infants receive insecure attachment classiﬁ  cations, these more severe forms of 
attachment disorder are rare.
Family relationships and parenting
Many other aspects of family life and relationships, and of parent-ing styles and behaviours, have been examined for their impact on children’s development. Research on families emphasizes the complexity of family relationships; each dyadic relationship is inﬂ uenced by other relationships in the family, and normative 
transitions in family life—the birth of a sibling, or mother starting work—reverberate to affect all family members.
(6) Relationships 
with parents and siblings change as children develop, and both these, and speciﬁ  c aspects of parenting, may impact on risks for 
disorder.
The implications of the most severely compromised parenting,

disorder.
The implications of the most severely compromised parenting, 
involving abuse or neglect, are examined in Chapter 9.3.3, and family-based risks for individual childhood disorders are discussed in detail in the chapters dealing with each speciﬁ  c condition. In 
general, these reﬂ  ect four broad themes:
◆ discordant, dysfunctional relationships between parents, or in 
the family system as a whole;
◆ hostile or rejecting parent-child relationships, or those markedly 
lacking in warmth;
◆ harsh or inconsistent discipline;
◆ ineffective monitoring and supervision.
Within this broad pattern, differential treatment of siblings is 
known to increase conﬂ  ict between children, and may have impor-
tant implications for psychopathology. In addition, outcomes are markedly poorer when children face multiple family-related risks.
Family life can also provide important sources of protective

Family life can also provide important sources of protective 
influences for children facing life events and other stressors. Cohesion and warmth within the family, the presence of one good relationship with a parent, close sibling relationships, and the nature of parental monitoring and supervision have all been found to show protective inﬂ  uences of this kind.
Parent and family characteristics
Psychopathology in parents is associated with increased risks of

Psychopathology in parents is associated with increased risks of 
emotional and behavioural problems in children. Recent estimates suggest that as many as 60 per cent of the children of parents with major depression will develop psychiatric problems in childhood or adolescence, and their risks of affective disorder are increased fourfold. Psychosis, alcohol and drug abuse, and personality disor-ders in parents are also associated with increased risks of disorder in offspring, and parental criminality is a strong risk factor for con-duct problems and delinquency.
In most instances, these links will reﬂ  ect a complex interplay 
between genetic and environmental effects. Disorder in parents is frequently associated with disturbed marital relationships, and parental psychopathology may also impair parenting capacities. Depressed mothers, for example, are less sensitive and responsive 
to their infants, and attend less, and respond more negatively, to

to their infants, and attend less, and respond more negatively, to 
older children. Alcohol and drug abuse and major mental disorders in parents may impair parenting in more wide-ranging ways. When parents are antisocial, effects may also be mediated through the endorsement of antisocial attitudes and social learning.Y oung maternal age is associated with increased risk for child 
and adolescent conduct problems. In part, these associations are likely to reﬂ  ect the educational and social disadvantages that pre-

dict very early parenthood; in part, the poor social conditions and lack of support faced by many young mothers; and in part, less than optimal parenting styles. Delinquency is also associated with large family size. Once again, the more proximal risks involved are likely to be complex: parental supervision may be less effective in large families, and opportunities to ‘learn’ from delinquent siblings higher. Beyond this, family size shows few consistent links with childhood disorder. Only children are not at increased psychiatric risk, and they share with other ﬁ  rst-borns some small advantages 
in terms of cognitive development. Birth order also appears to have few implications for behavioural adjustment, although youngest children show some increased rates of school refusal.
Changing family patterns

Recent decades have seen massive changes in the pattern of many children’s family lives. The most obvious markers are the dramatic increases in rates of divorce, single parenthood, and step-family formation, along with major increases in maternal employment. In the years immediately after the Second World War, just 6 per cent of British couples divorced within 20 years of marriage. By the mid-1960s that ﬁ  gure had increased four-fold, and divorce rates 
continued to rise into the 1980s. For most children, parental divorce will be followed by a period in a single-parent household; for a substantial minority, further family transitions will mean that they become part of a step family. In the early years of the 21st century more than 10 per cent of UK families with dependent children were step-families, and approaching a quarter of children lived in single parent households.
Parental divorce

There is now extensive evidence that divorce is associated with neg-ative consequences for children.
(7) Psychological and behavioural 
distress are common, especially in the period immediately follow-ing divorce; more severe disturbance is not. Boys in particular are at increased risk for conduct problems. Educational attainments and motivation are often compromised, and subsequent relation-ships may also be affected. As they approach adulthood, children of divorce move into close relationships earlier than their peers, but also experience higher risks of relationship breakdowns.
Events both before and after the separation seem central in 
understanding these effects. Longitudinal studies, for example, have shown that children in divorcing families often show dis-turbed behaviour well before their parents separate. Exposure to the discord and conﬂ  ict that frequently precede divorce thus seem 
to be key components of risk. After separation, problematic rela-

tionships between parents may continue, and the parents’ own dis-
tress may compromise their capacity to respond sensitively and consistently to their children’s needs. Many families face a sharp decline in economic circumstances after divorce, and for many children their parents’ separation may involve house moves, school changes, and other disruptions to their established social networks. Each of this constellation of factors may contribute to subsequent outcomes.
Single parents and step families
Research on the effects of growing up in single-parent and step families illustrates the complexity of family-related inﬂ  uences.
(8)

1727
Overall, children in single-parent and step families show higher 
mean levels of emotional and behavioural problems than those in non-divorced two-parent families; they also have an increased probability of health problems and educational underachievement. But there are also marked differences within each family type and associations between the quality of mother–child relationships and children’s adjustment is similar across family settings. In addition, single-parent and reconstituted families often differ from stable two-parent families in a plethora of other ways; in particular, they are much more likely to face economic pressures, poor social support, and higher levels of maternal depression. Once these variations and the degree of negativity in family relationships are taken into account, family type per se  shows few consistent links 
with children’s adjustment.
Peer inﬂ  uences
Beyond the family, relationships with peers are now recognized to

Beyond the family, relationships with peers are now recognized to 
provide a unique and essential contribution to children’s social, emotional, and cognitive development.
(9) By the end of the 
pre-school period most children have at least one reciprocated friendship. In childhood and adolescence, peers take on increasing importance; in middle childhood, more than 30 per cent of children’s social interactions are with peers, and adolescents are estimated to spend more than twice as much time with peers than they do with parents or other adults. The functions of friendship change with development, expanding to encompass companionship and stimulation, help and sharing, social and emotional support and intimacy.
With friends and peers children acquire skills, attitudes, and

With friends and peers children acquire skills, attitudes, and 
experiences that contribute to many aspects of their adaptation. By the same token, children who have poor social skills, or who are rejected or neglected by peers, are at risk of a range of adverse outcomes including poor school performance, school drop-out, 
and psychiatric disorder. Social rejection may increase children’s 
feelings of loneliness, reduce supports that can buffer against stres-sors, and also mean that isolated children miss out on important social learning experiences. Since many children with psychiatric disorders also show difﬁ  culties in relationships with peers, proc-
esses of this kind may well compound their problems. In adoles-cence, afﬁ  liations with behaviourally deviant peers have attracted 
particular interest as correlates of conduct disorder and delinquency. Here, reciprocal inﬂ  uences have been demonstrated: aggressive

particular interest as correlates of conduct disorder and delinquency. Here, reciprocal inﬂ  uences have been demonstrated: aggressive 
disruptive children are more likely to associate with deviant peers, but relationships with peers also show an independent effect on both the onset and persistence of delinquency.
Child care and schooling
By the late 1990s approaching 50 per cent of mothers in the UK returned to full- or part-time work before their infants reached one year of age. This major increase in early maternal employment has prompted extensive research on the impact of alternative childcare on children’s development. Recent evidence
(10) suggests that multi-
ple features of early care need to be considered in assessing effects. Higher child-care quality  (as indexed by features such as sensitive

ple features of early care need to be considered in assessing effects. Higher child-care quality  (as indexed by features such as sensitive 
and responsive care-giving, and cognitive and language stimula-tion), is associated with improved performance on tests of cogni-tive, language, and early academic skills, and with more prosocial skills and fewer behaviour problems, By contrast, higher quantityof child care (as indexed by hours per week in any kind of non-mater-
nal care), is associated with some increased risks of problem behav-iours in both the preschool and early school years.
School life then brings its own demands and challenges. Starting 
and changing schools are signiﬁ  cant, sometimes troublesome, 
events for children; although most young children adapt well, a signiﬁ  cant minority show some disturbance when they start school, 
and both attainment levels and self-perceptions are affected for

and both attainment levels and self-perceptions are affected for 
many young adolescents after the transition from primary to secondary school. T ests and examinations rank high on children’s lists of fears, and levels of psychological distress are elevated at times of major examinations. Although fears of this kind are not generally severe, they do show links with clinically signiﬁ  cant 
symptoms. Bullying is a further problem especially associated with the school context. Self-report surveys suggest that over 15 per cent of young children experience some bullying at school, mostly unknown to parents or teachers. Although rates fall with age, up to 5 per cent of adolescents continue to face bullying in secondary school. Persistently victimized children have identiﬁ  able character-

istics, with histories of anxious insecure behaviours and social isolation often beginning before they started school; bullying then increases their risks of adjustment problems.
Like families, schools differ in their atmosphere and social 
climate, and these variations show an independent impact on children’s academic progress and behaviour. In part, these varia-tions reﬂ  ect differences in initial pupil intakes. In addition, they 
show systematic links with organizational characteristics of schools. Schools with more positive outcomes are characterized by purpose-ful leadership, constructive classroom management techniques, an appropriate academic emphasis, and consistent but not overse-vere sanctions. In relation to behavioural outcomes, the composi-tion of pupil groupings may also be inﬂ  uential. Y oung children are 
more likely to become aggressive if placed in highly aggressive classes, and risks of delinquency are increased in secondary schools

more likely to become aggressive if placed in highly aggressive classes, and risks of delinquency are increased in secondary schools 
where intakes include large proportions of less able children. For 
some severely disadvantaged groups, however, schooling may offer an important source of positive experiences. Experimental studies of preschool programmes, for example, have shown impor-tant long-term gains in terms of reduced risks of delinquency and unemployment many years after participants left school.
Wider social and environmental inﬂ  uences
Poverty and social disadvantage
Poverty and social disadvantage are most strongly associated with 
deﬁ cits in children’s cognitive  skills and educational achievements.(11)
In the behavioural domain, disruptive behaviours also show

In the behavioural domain, disruptive behaviours also show 
links with family poverty. Effects appear to be more marked for boys than for girls, and seem to be stronger in childhood than in adolescence. Intermittent hardship is associated with some increased risk for conduct problems, but the impact is most marked for children in families facing persistent economic stress. Most current evidence suggests that these effects are indirect. Poverty imposes stress on parents, and reduces the supports available to them; these in turn increase the risks of harsh or coercive parent-ing, and reduce parents’ emotional availability to their children’s needs. Some studies suggest that relative deprivation—the percep-tion that one is disadvantaged by comparison with others—may be more important than income levels per se .9.3.1 the influence of family, school, and the environment

SECTION 9  child and adolescent psychiatry 1728
Neighbourhood and community contexts
Rates of childhood disorder vary in different neighbourhoods and 
communities. Urbanization is frequently associated with increased risks of disorder, and rates may be especially high in chronically dis-advantaged inner-city neighbourhoods. In early childhood, many of these effects seem to be indirect; neighbourhood disadvantage increases stress on families, and these in turn largely account for associations with children’s difﬁ  culties. In severely disadvantaged 
settings, however, even quite young children may be directly exposed to community violence, and in adolescence, neighbourhood inﬂ  u-
ences may be mediated through associations with delinquent peers.
Multiple stressors

For many children, exposure to these differing types of adversity will covary. Stressed families frequently live in poor neighbourhoods, where schools are under pressure and peer groups deviant. Early epidemiological ﬁ  ndings suggested that isolated single risks have 
relatively little impact on disorder, but that rates rise sharply when risk factors combine. More recently, studies have shown that child, sociocultural, parenting, and peer-related risks each add uniquely to the prediction of behaviour problems. In addition, the total number of risks a child faces explains further variance in outcomes.
Secular trends in disorder and psychosocial risks

Finally, it is important to consider how psychosocial risks may impact on overall levels of disorder. There is now clear evidence that rates of many adolescent disorders—including depression, suicide, alcohol and drug use, and delinquency—have risen since the Second World War.
(12) Since it is implausible that changes in the gene pool 
could occur so rapidly, environmental risk factors must be implicated. Some of these may overlap with risks for individual differences in disorder, but others may be quite distinct. Based on an extensive review of available evidence, Rutter and Smith
(12) concluded that 
a variety of factors are likely to be implicated:
1 increased rates of family breakdown, with their associated effects 
on the disruption of relationships and exposure to conﬂ  ict and 
discord;
2 a change in the meaning of adolescence, with prolonged educa-

discord;
tion and economic dependence on parents occurring alongside increased autonomy in other spheres;
3 a possibly increased disparity between young people’s aspirations 
and the opportunities available to meet them;
4 increased alcohol consumption and illegal drug use;
5 changing social attitudes to acceptable behaviour, possibly 
enhanced by inﬂ  uences from the mass media.
Other speciﬁ  c factors may affect rates of juvenile crime. In particular, 
the increasing commercialization of youth culture, providing more goods to steal, may have coincided with diminished surveil-lance and increased situational opportunities for property crime.
Clarke-Stewart, A. and Dunn, J. (2006). Families count: effects on child and 
adolescent development . Cambridge University Press, Cambridge.

Rutter M. (2005). Environmentally mediated risks for psychopathology: 
Research strategies and ﬁ  ndings. Journal of the Amrican Academy of Child 
and Adolescent Psychiatry, 44, 3–18.References
 1. Lytton, H. (1990). Child and parent effects in boys’ conduct disorder: a 
reinterpretation. Developmental Psychology ,5, 683–97.
 2. Scarr, S. and McCartney, K. (1983). How people make their own 
environments: a theory of genotype–environment effects. Child
Development ,54, 424–35.
 3. Plomin, R. and Bergeman, C.S. (1991). The nature of nurture. Genetic 
inﬂ uences on ‘environmental’ measures. Behavioural and Brain Sciences ,
14, 373–86.
 4. Rutter, M., Mofﬁ  tt, T., and Caspi, A. (2006). Gene–environment 
interplay and psychopathology: Multiple varieties but real effects. Journal of Child Psychology and Psychiatry ,47, 226–61.

4. Rutter, M., Mofﬁ  tt, T., and Caspi, A. (2006). Gene–environment 
 5. Bowlby, J. (1988). A secure base: clinical applications of attachment 
 6. Dunn, J. (1994). Family inﬂ  uences. In Development through life: a 
handbook for clinicians  (eds. M. Rutter and D.F. Hay), pp. 112–31. 
 7. Rodgers, B. and Pryor, J. (1998). Divorce and separation: the outcomes 
for children . Joseph Rowntree Foundation, Y ork.
 8. Dunn, J., Deater-Deckard, K., Pickering, K., et al. (1998). Children’s 
adjustment and prosocial behaviour in step–, single-parent, and non-stepfamily settings: ﬁ  ndings from a community study. Journal of Child 
Psychology and Psychiatry ,39, 1083–95.
 9. Rubin, K.H., Bukowski, W., and Parker, J.G. (1998). Peer interactions, 
relationships, and groups. In Handbook of child psychology , Vol. 3

relationships, and groups. In Handbook of child psychology , Vol. 3 
Social, emotional and personality development  (ed. N. Eisenberg), 
pp. 619–700. Wiley, New Y ork.
10. NICHD Early Child Care Research Network (2006). Child-care 
effect sizes for the NICHD Study of Early Child Care and Y outh Development. American Psychologist, 61, 99–116.
11. Duncan, G.J. and Brooks-Gunn, J. (ed.) (1997). Consequences of 
growing up poor . Russell Sage, New Y ork.
12. Rutter, M. and Smith, D.J. (1995). Psychosocial disorders in young people: 
times trends and their causes . Wiley, Chichester.
9.3.2 Child trauma
Children’s reactions to traumatic events
This chapter will focus on the impact on children of traumatic 
events other than child abuse or neglect, which are covered in Chapter 9.3.3. According to the DSM-IV-TR deﬁ  nition of post-

traumatic stress disorder (PTSD), traumatic events involve expo-sure to actual or threatened death or injury, or a threat to physical integrity. The child’s response generally involves an intense reac-tion of fear, horror, or helplessness which may be exhibited through disorganized or agitated behaviour. T err suggested separating trau-matic events into type I traumas which are single sudden events and type II traumas which are long-standing or repeated events.
(1)
If the traumatic event includes bereavement, the reactions may 
be complicated and readers should consult Chapter 9.3.7 to address the bereavement aspects of the event.
Following a traumatic event, children may react in a variety of

Following a traumatic event, children may react in a variety of 
ways (see Chapters 4.6.1 and 4.6.2 for the adult perspective on reac-tions to stressful and traumatic events). Many show some of the symptoms of post-traumatic stress disorder—re-experiencing the

1729
event (e.g. through nightmares, ﬂ  ashbacks, intrusive thoughts, 
re-enactment, or repetitive play of the event), avoidance and numb-ing (e.g. avoidance of conversations, thoughts, people, places, and activities associated with the traumatic event, inability to remember a part of the event, withdrawal from previously enjoyed activities, feeling different from others, restriction of emotions, sense of foreshortened future), and physiological arousal (e.g. sleep disturbance, irritability, concentration problems, being excessively alert to further danger, and being more jumpy). In young children the nightmares may become general nightmares rather than trauma-speciﬁ  c. Other reactions to trauma in children are:
◆ becoming tearful and upset or depressed
◆ becoming clingy to carers or having separation anxiety
◆ becoming quiet and withdrawn
◆ becoming aggressive
◆ feeling guilty
◆ acquiring low self-esteem
◆ deliberately self-harming
◆ acquiring eating problems

◆ feeling as if they knew it was going to happen
◆ developing sleep disturbances such as night-terrors or 
sleepwalking
◆ dissociating or appearing ‘spaced out’
◆ losing previously acquired developmental abilities or regression
◆ developing physical symptoms such as stomach aches and headaches
◆ acquiring difﬁ  culties remembering new information
◆ developing attachment problems
◆ acquiring new fears
◆ developing problems with alcohol or drugs.
Such problems may individually or in combination cause 
substantial difﬁ  culties at school and at home. The reactions of

substantial difﬁ  culties at school and at home. The reactions of 
some children will diminish over time; however, for some they will persist, causing distress or impairment, warranting diagnosis, and/or intervention. Research predicting which children will be more likely to be distressed following a traumatic event suffers from a number of methodological ﬂ  aws. However, factors which are often 
identiﬁ  ed as constituting a risk for developing PTSD across a 
number of studies include: level of exposure, perceived level of threat and peri-traumatic fear, previous psychological problems, family difﬁ  culties, co-morbid diagnoses, subsequent life events, 
and lack of social support.
Diagnosis of PTSD
Both DSM-IV-TR and the ICD-10 diagnostic classiﬁ  cation of

Both DSM-IV-TR and the ICD-10 diagnostic classiﬁ  cation of 
PTSD are appropriate for use with adults and although children from 8 years old do display similar symptoms to adults
(2) there are 
some developmental differences particularly in younger children.(3)
Alternative diagnostic criteria for pre-school children have there-fore been developed, which draw on reports by carers and include more behavioural symptoms such as loss of developmental skills, and development of new fears or anxiety.
(4)Other diagnoses
Careful assessment is required to make an accurate differential diagnosis. According to DSM-IV-TR, PTSD can only be diagnosed 1 month after the event, prior to that a diagnosis of acute stress disorder (ASD) may be appropriate. Whereas ICD-10 PTSD can be diagnosed within the ﬁ  rst month, and the acute stress reaction is

reserved to describe a disturbance that resolves rapidly. If the event is not of sufﬁ  cient severity to meet the criteria for PTSD and the 
reaction does not last more than 6 months after the stressor has ceased, then a diagnosis of adjustment disorder may be appropri-ate. Recovery may take longer for children if their parents continue to suffer from symptoms of PTSD which may constitute a chronic source of stress which may in turn prolong the symptoms of the child. Further information on these diagnoses from an adult per-spective can be found in Chapters 4.6.1–4.6.5.
Other diagnosable disorders may result from traumatic events, 
and may be present singularly or co-morbidly with PTSD; 60 per cent 
of children with PTSD have a co-morbid mental health diagnosis.
(5)
According to Fletcher’s meta-analysis, common co-morbid diagno-ses are: anxiety disorders, depression, alcohol and drug abuse in adolescents, and attention deﬁ  cit hyperactivity disorder (ADHD).
(2)

(2)
As with other psychiatric disorders, the best assessment can be made 
by integrating information from a number of sources such as an interview of the parent/carer alone, an interview of the family togeth-er, information from school, and information from psychological measures (see below). Careful consideration should be given to which members of the family will be involved in any interviews so as to avoid exposing previously unaffected children to the traumatic details of the event. Sometimes children try to ‘protect’ their carers from dis-tress by under-reporting their symptoms of trauma, it is therefore also essential to interview the child on their own where possible.
(6)
In order to assess what elements of the child’s current function-

(6)
ing and distress may be a result of the traumatic event, and those that may pre-date it, it is important to gain as full a picture as possible of their developmental history and their pre-morbid functioning. Reports from teachers and other professionals may be particularly useful in this respect.
On assessment, some account of the traumatic event is necessary 
so that the clinician can gain an understanding of what exactly was experienced. Furthermore, it is helpful to give the sense that the clinician can bear to hear a story which the child and family may have been avoiding to tell for some time. However, this must be balanced against the child’s understandable avoidance of the memory. There is little point gaining a full account of the event during the assessment, if the child becomes so distressed that they 
do not return for treatment. Pynoos and Eth offer a structure for

do not return for treatment. Pynoos and Eth offer a structure for 
conducting such an initial assessment which begins with a projec-tive drawing and storytelling. It then proceeds to discussion of the actual event and its impact, followed by closure.
(7) If the assess-
ment has included talking about the traumatic event the child and family may become very distressed, and it may be necessary to invest some time in winding down the session, so that the family does not leave overly distressed. This will increase the likelihood of 
them engaging in the treatment process, which is likely to involve thinking through the event—something which they often do not intuitively want to do.9.3.2 child trauma

SECTION 9  child and adolescent psychiatry 1730
Assessment includes asking about the motivation for the 
contact with the service. Unlike many other problems, families with traumatized children may not simply present at the service in order to effect a change in their child’s symptoms. They may be asking for advice following a traumatic event to try and prevent problems from appearing later by ensuring that they are ‘doing the right thing’ , or they may be seeking an assessment for the purpose of compensation or other legal purposes.
Psychological instruments

A number of questionnaires and diagnostic interviews are available to assist in the assessment of PTSD. Such instruments cannot replace a clinical interview, but may assist by strengthening clinical opinion and giving a reliable and valid indication of perceived symptom severity or frequency. This can give an indication of the impact of an event, can raise hypotheses which can be further investigated (e.g. screening for possible presence of PTSD which can then be further assessed) and if repeated after treatment can help to measure change. Ohan and colleagues reviewed those measures used in research studies that have adequate psychometric properties.
(8) The best diagnostic instrument is the children’s PTSD 
inventory. This is a structured diagnostic interview, the psycho-metric properties of which are good and have been published in peer-reviewed journals.
(9,10)  The Children’s Revised Impact of

(9,10)  The Children’s Revised Impact of 
Events scale(11) is a useful self-report questionnaire of 13 items 
appropriate for children aged 8 years and above. It has good screen-ing properties
(12) and is freely available from the Children and 
War Foundation’s website (see below). Similarly Foa’s Child PTSD Symptom scale (CPSS) is a 24-item self-report questionnaire designed for children aged 8 years and above. It is emerging as having good psychometric properties.
(13) The CPSS has the advan-
tage of speciﬁ  cally assessing the symptoms of PTSD from the 
DSM-IV-TR, and unlike most other self-report measures, it also addresses the important question of the impact of the symptoms on the child’s functioning.

An increasing amount of evidence indicates that trauma-focussed cognitive behavioural therapy (TF-CBT) is the treatment of choice for PTSD.
(14) Much of the evidence is from studies of children with PTSD 
as a result of child sexual abuse. Dalgleish and colleagues summarize the evidence thus; ‘The current take-home message from this nascent literature therefore is that CBT appears to have well-established efﬁ  -
cacy in treating a range of post-traumatic stress responses following sexual abuse, with preliminary evidence in favour of this form of intervention following other types of trauma’ .
(15) Consequently, 
TF-CBT is the only intervention recommended by the United Kingdom’s National Institute for Health and Clinical Excellence (NICE) for the treatment of children and young people with PTSD.
(6)

(6)
Family therapy and psychodynamic psychotherapy as stand 
alone therapies for children with PTSD are not currently supported by the same level of evidence as TF-CBT. However, there is evidence to illustrate the importance of involving parents or carers in treatment where appropriate.
(16) Psychodynamic psychotherapy 
may have some contribution to the treatment of traumatized chil-dren
(17) and clinical experience indicates this to be true particularly 
in children with co-morbid diagnoses or where the traumas are multiple and prolonged (type II) such as in war and civil conﬂ  icts, 
and have led to failures of basic care.Eye Movement Desensitisation and Reprocessing (EMDR) has 
proven to be effective with adults and has increasingly been used with children.

(18) It shows promise for use with children and young people, 
but it has not yet established the same level of evidence as TF-CBT.(6)
The available evidence does not currently support the use of 
medication to treat PTSD in children or young people,(6) although 
medication may be necessary to treat any co-morbid conditions such as depression, ADHD, or sleep problems.
Trauma-focussed cognitive behavioural 
therapy (TF-CBT)
‘Processing’ of an event involves bringing the event to mind and

‘Processing’ of an event involves bringing the event to mind and 
thinking it through often by talking, writing, or playing. This enables the memory to be stored as an ordinary narrative memory which is under the child’s control, rather than as the vivid sensory informa-tion of the original event which is prone to being involuntarily re-experienced. Furthermore, processing enables a more helpful mean-ing to be attributed to the event; so whilst it may well be thought of as ‘terrifying’ and ‘unfortunate’ , it no longer colours the way that everything  in the child’s world, including him or herself is seen.
Many children will process difﬁ  cult and traumatic experiences 
naturally, often with the help of those around them such as their car-ers. Some may take a little while to do so. However, bringing up the memory may initially trigger the fear or distress of the original event,

so some children avoid thinking about it, which in turn prevents processing.
(19) Similarly the adults around the child may try to pro-
tect either themselves or the child from further distress by not dis-cussing the event and so opportunities to enable the child to process it may be missed through avoidance by proxy. Therefore some chil-dren will not manage to process the event without professional help.
TF-CBT for traumatized children and families involves enabling 
the child or young person to bring the traumatic event to mind within the safe environment of therapy. This is akin to exposure  to 
the memory, which enables the memory to be processed. Cognitive 
restructuring  involves enabling the child to alter their unhelpful 
negative view of themselves or the world, which is based on the event, to a more helpful and realistic one. Cognitive behavioural therapy for children is further described in Chapter 9.5.3, Stallard provides excellent resources in the form of a workbook,

(20) and 
Cohen offers a comprehensive description of the treatment of trauma and traumatic grief.
(21)
Y ounger children with PTSD may not be able to make use of 
TF-CBT in the same way that older children can, and their treat-ment is likely to involve much more family work and ensuring that they learn that their environments are safe through re-assurance and stability.
(22)
Early interventions
There continues to be much debate about the value of early intervention (i.e. within the ﬁ  rst month). Research to date does not 
support the use of single session debrieﬁ  ng,
(23) however, there may 
be value in the provision of practical and emotional support in the immediate aftermath, together with some education of what reac-tions can be expected. Development of a culture where the child is permitted, or encouraged to talk about the event (e.g. within the family or within the school) may protect against the development of PTSD.
(24) Early trauma-focussed cognitive behavioural therapy

(24) Early trauma-focussed cognitive behavioural therapy 
may be offered to older children with the most severe symptoms(6)

1731
which may be completed in groups (e.g.(25)). There may be a role 
for EMDR in the early stages following a traumatic event, although this has yet to receive empirical support.
Dyregrov, A. (2006). Grief in Children: a handbook for adults , (2nd edn) 
London, Jessica Kingsley Publishers.
Salmon, K. and Bryant, B.A. (2002). Posttraumatic stress disorder in 
children. The inﬂ  uence of developmental factors. Clinical Psychology 
Review ,22, 163–88.
The National Child Traumatic Stress Network. An American based network 
that provides excellent resources for parents, schools, the media, and professionals. www.nctsnet.org
The Children and War Foundation. This is a charity which aims to improve 
the care of children affected by war and disaster. Two professional

the care of children affected by war and disaster. Two professional 
groups, the Center for Crisis Psychology in Bergen, Norway and the Institute of Psychiatry in London, UK, have been instrumental in setting up this foundation. Copies of the Children’s Revised Impact of Events scale (CRIES), the Depression Self-rating Scale for Children and the Revised Children’s Manifest Anxiety scale (RCMAS) are available free from the website in various languages. www.childrenandwar.org
 1. T err, L.C. (1991). Childhood traumas: an outline and overview. The
American Journal of Psychiatry ,148(1), 10–20.
 2. Fletcher, K.E. (1996). Childhood post-traumatic stress disorder. In 
Child psychopathology  (eds. E.J. Marsh and R. Barkley), pp. 242–76. 
 3. Salmon, K. and Bryant, R.A. (2002). Posttraumatic stress disorder in 
children. The inﬂ  uence of developmental factors. Clinical Psychology

Review ,22(2), 163–88.
 4. Scheeringa, M.S., Zeanah, C.H., Myers, L., et al. (2003). New ﬁ  ndings 
on alternative criteria for PTSD in preschool children. Journal of the 
American Academy of Child and Adolescent Psychiatry ,42(5), 561–70.
 5. AACAP . (1998). Practice parameters for the assessment and treatment 
of children and adolescents with posttraumatic stress disorder. 
37(Suppl. 10), 4S–26S.
 6. NICE. (2005). The management of PTSD in adults and children in 
primary and secondary care . National Clinical Practice Guideline 26. 
Gaskell & BPS.
 7. Pynoos, R.S. and Eth, S. (1986). Witness to violence: the child interview. 
25(3), 306–19.

 8. Ohan, J.L., Myers, K., and Collett, B.R. (2002). T en-year review of 
rating scales. IV: scales assessing trauma and its effects. Journal of the 
American Academy of Child and Adolescent Psychiatry ,41(12), 
1401–22.
 9. Y asik, A.E., Saigh, P .A., Oberﬁ  eld, R.A., et al. (2001). The validity of the 
children’s PTSD inventory. Journal of Traumatic Stress ,14(1), 81–94.
10. Saigh, P .A., Y asik, A.E., Oberﬁ  eld, R.A., et al. (2000). The children’s 
PTSD inventory: development and reliability. Journal of Traumatic 
Stress ,13(3), 369–80.
11. Smith, P ., Perrin, S., Dyregrov, A., et al. (2003). Principal components 
analysis of the impact of event scale with children in war. Personality 
and Individual Differences ,34, 315–22.
12. Perrin, S., Meiser-Stedman, R., and Smith, P . (2005). The children’s

12. Perrin, S., Meiser-Stedman, R., and Smith, P . (2005). The children’s 
revised impact of event scale (CRIES): validity as a screening instrument 
for PTSD. Behavioural and Cognitive Psychotherapy ,33(4), 487.
13. Foa, E.B., Johnson, K.M., Feeny, N.C., et al. (2001). The child PTSD 
symptom scale: a preliminary examination of its psychometric properties. Journal of Clinical Child Psychology ,30(3), 376–84.
14. Stallard, P . (2006). Psychological interventions for post-traumatic 
reactions in children and young people: a review of randomised controlled trials. Clinical Psychology Review ,26(7), 895–911.15. Dalgleish, T., Meiser, S.R., and Smith, P . (2005). Cognitive aspects 
of posttraumatic stress reactions and their treatment in children 
and adolescents: an empirical review and some recommendations. Behavioural and Cognitive Psychotherapy ,33(4), 459.

16. Cohen, J.A. and Mannarino, A.P . (1998). Factors that mediate 
treatment outcome of sexually abused preschool children: six- and 12-month follow-up. Journal of the American Academy of Child and 
Adolescent Psychiatry ,37(1), 44–51.
17. Trowell, J., Kolvin, I., Weeramanthri, T., et al. (2002). Psychotherapy 
for sexually abused girls: psychopathological outcome ﬁ  ndings and 
patterns of change. The British Journal of Psychiatry ,180(3), 234.
18. Tufnell, G. (2005). Eye movement desensitization and reprocessing 
in the treatment of pre-adolescent children with post-traumatic symptoms. Clinical Child Psychology and Psychiatry ,10(4), 587.
19. Meiser-Stedman, R. (2002). T owards a cognitive-behavioral model of 
PTSD in children and adolescents. Clinical Child and Family Psychology 
Review ,5(4), 217–32.

20. Stallard, P . (2002). Think good—feel good: a cognitive behaviour therapy 
workbook for children and young people . John Wiley and Sons Ltd., 
21. Cohen, J.A., Mannarino, A.P ., and Deblinger, E. (2006). Treating trauma 
and traumatic grief in children and adolescents . Guilford Press, New Y ork.
22. Scheeringa, M.S. (1999). Treatment for posttraumatic stress disorder 
in infants and toddlers. Journal of Systemic Therapies ,18(2), 20–31.
23. Stallard, P ., Velleman, R., Salter, E., et al. (2006). A randomised 
controlled trial to determine the effectiveness of an early psychological 
intervention with children involved in road trafﬁ  c accidents. Journal of 
Child Psychology and Psychiatry ,47(2), 127–34.
24. Dyregrov, A. (2001). Early intervention—a family perspective. 
Advances ,17(3), 168–74.

25. Giannopolou, I., Dikaiakou, A., and Yule, W. (2006). Cognitive-
behavioural group intervention for PTSD symptoms in children 
following the Athens 1999 earthquake: a pilot study. Clinical Child 
Psychology and Psychiatry ,11, 543–53.
9.3.3 Child abuse and neglect
Child abuse and neglect (child maltreatment) is a combination of 
a consensus about what comprises unacceptable child rearing/care, together with what children have a right to be free from. This is made explicit in the United Nations Convention on the Rights of the Child,
(1) which sets out basic rights and standards for judging 
children’s welfare, including, but not limited to, maltreatment. It incorporates both maltreatment of children within families and that arising from wider social inﬂ  uences, including child labour

children’s welfare, including, but not limited to, maltreatment. It incorporates both maltreatment of children within families and that arising from wider social inﬂ  uences, including child labour 
and sexual exploitation, and children in war zones.
(1)
Maltreatment affects the healthy and normal course of develop-
ment. It causes deviation from an expected trajectory, preventing the developing child’s negotiation of sequential tasks and disrupt-ing normal transaction between different facets of development.
(2)
Therefore maltreatment is the very antithesis of adequate child care and rearing, posing a major public health threat.
(3)
Adequate rearing of the young is such a fundamental activity 
that the state must be concerned with the overall welfare of children within its society; in family settings where they are normally brought up, and in schools, hospitals, and residential settings. 9.3.3 child abuse and neglect

SECTION 9  child and adolescent psychiatry 1732
While the Convention provides a framework, several states have 
developed a children’s ombudsman, with wide-ranging powers to oversee the status of children’s welfare and to tackle obstacles to it.
There are laws within each society to regulate the care and 
welfare of children, specifying the consequences if children are maltreated. In England and Wales, the Children Acts 1989, and 2004 address the overall welfare of children, including those deemed in need of extra help and support, and provide a legislative structure for those children who are at risk of, or are actually being, signiﬁ  cantly harmed (child maltreatment).
Countries vary in their response to child maltreatment. In the

Countries vary in their response to child maltreatment. In the 
United States, any professional who has reason to suspect that a child is being maltreated is legally required to inform the local child welfare agency (mandatory reporting). Some countries in Europe (e.g. Belgium and Holland) have a system whereby child-maltreatment concerns are dealt with conﬁ  dentially, through health 
and social care supportive systems, rather than through primarily legal methods. The United Kingdom lies between these extremes, but relatively closer to the United States model than to the ‘conﬁ  -
dential doctor’ system. Whatever system is in place, it is clear from the scope of the problem of child maltreatment that multidisci-plinary working is a core requirement.
A developmental-ecological model is the most useful conceptual 
framework, which draws together the various factors known to contribute or be associated with the predisposition, occurrence, 
course and effects of child maltreatment.

(3,4) It incorporates indi-
vidual and interpersonal factors, family inﬂ  uences, immediate 
neighbourhood ones, together with broader social inﬂ  uences on 
child rearing and care. However, these layers of increasing social complexity, which surround the individual child, are not static. In addition to transactions between factors, there are important inﬂ uences historically, and subsequent to any maltreatment, which 
have an impact on outcome. This inclusive conceptual framework enables genetic and environmental factors to be integrated in a manner that can inform clinical assessment and intervention.
Types of maltreatment
Identiﬁ  cation of different types of maltreatment may be necessary 
for social and legal purposes, but epidemiologically, co-occurrence of varieties of maltreatment is more usual than singularity.

(3,5)
Ofﬁ cial registers often record predominant type or that perceived 
to be the most serious. This knowledge is one of several method-ological problems that affect confidence in research findings. However separate types are retained here, for descriptive purposes, while encouraging the reader to consider likely overlap in individual cases.
Accurate ﬁ  gures for incidence and prevalence are bedevilled by 
ascertainment and recording difﬁ  culties, including secrecy and 
shame which are often associated. These inﬂ  uences are illustrated 
by the wide gulf between incidence and prevalence rates.(3)
Incidence rates increase from reported cases to higher rates

Incidence rates increase from reported cases to higher rates 
obtained from representative community samples. The incidence of signiﬁ  cant violence to children varies between 50 to 90 per thou-
sand across cultures in community samples, and dropping to the mid-20s per thousand for cases known to professionals working with children. Cases known to social welfare agencies departments only comprise a minority of these. However, ofﬁ  cially reported 
maltreatment ranges from 2 to 12 per thousand in England, North America and Australia. Neglect is commonest (34 to 59 per cent of cases); physical abuse (15 to 28 per cent); sexual (10 to 28 per cent); and emotional (7 to 34 per cent).
Most prevalence ﬁ  gures for each of physical, emotional and

Most prevalence ﬁ  gures for each of physical, emotional and 
neglect range between 5 and 10 per cent. The equivalent rate for contact sexual abuse is 10 per cent (15 per cent of girls; 5 per cent of boys). Children with a disability are three times more likely to be maltreated.
(3)
Life-threatening maltreatment rates have remained relatively 
constant, currently 0.1 to 2.2/1000 children in industrialized countries, rising to two to three times this in low to mid-income countries. Children are at their most vulnerable during infancy and neonatal periods.
Child sexual abuse
This is deﬁ  ned as sexual activities which involve a child and an 
adult, or a significantly older child. There are two elements: the sexual activities and the abusive condition.
(6) Contact sexual

(6) Contact sexual 
activities include penetrative acts (e.g. penile, digital, or object penetration of the vagina, mouth, or anus) and non-penetrative acts (e.g. touching or sexual kissing of sexual parts of the child’s body, or through the child touching sexual parts of the abuser’s body). Non-contact sexual activities include exhibitionism, involv-ing the child in making or consuming pornographic material, or encouraging two children to have sex together.
The abusive condition is founded on the premise that children 
cannot generally give consent to sex, because of their dependent condition. Consent can be difﬁ  cult to assess in older children or

cannot generally give consent to sex, because of their dependent condition. Consent can be difﬁ  cult to assess in older children or 
if there is a small age gap between abuser and abused. Considering whether exploitation has occurred can aid this decision: it com-prises misuse of authority or age differentials through deceit, 
unreasonable persuasion, coercion, or overt force.
Half the sexual abuse cases coming to the attention of welfare 
agencies involve penetration or orogenital contact. The proportion is less in community samples, because reported cases tend to be more serious in nature.
Abuse perpetrated by a caretaking adult normally consists of 
increasingly severe sexual contact over time, with parallel increases in coercion and threats to the child if the ‘secret’ is disclosed. As the physical acts and psychological climate worsen, so the child’s reluc-tance to disclose the predicament deepens.
Diagnosis

Diagnosis
The most common presentation is through a statement from the child.
(7) Unless the child is responded to sympathetically at this 
point, they may be reluctant to reveal the full nature of their plight. More than half of those who are abused do not disclose the fact, especially if they are male.
Less commonly the child’s behaviour can draw attention to 
abuse, particularly if the child shows sexual behaviour problems, either directed towards themselves or towards other children. However, behaviour and emotional difﬁ  culties are normally non-
speciﬁ  c, occurring in about two-thirds of children. Older children 
and adolescents show behaviour difﬁ  culties which are unexpected 
for themselves or their peer group, including substance abuse, suicide attempts, running away from home, or becoming unpredictably

1733
out of control. Not surprisingly, high rates of prior sexual abuse are 
noted among young people involved in prostitution.
Medical presentations do occur, for instance venereal diseases, 
evidence of acute assault, or an otherwise unexplained pregnancy.
Prior to investigation, one-third of reported cases are already 
known to child welfare agencies for other reasons. Children are more likely to disclose their predicament if they have ﬁ  rst made 
a spontaneous statement to someone before being interviewed by professionals.
Child psychiatric services may assist social workers interviewing 
children and young people with a psychiatric disorder, or very young children. Other specialists should be enlisted for those with communication problems and learning difﬁ  culties. The aim of 
interviewing is to help a child describe their predicament whilst avoiding suggestion.
(8) Child psychiatry also has a role to play in

(8) Child psychiatry also has a role to play in 
providing psychological treatments for symptomatic children and working with disturbed families.
Screening for the possibility of child sexual abuse increases 
recognition in both adult and child populations, revealing infor-mation that can be essential for psychiatric management. Adult services have a role to play in addressing psychiatric problems in family members, including treatment for paraphilias, often in con-junction with the probation service or other specialized provision.
Aetiological and background factors
(a) Characteristics of abused children
Sexual abuse affects children of both sexes and all ages. The most common age when children are abused is between the ages of 7 and 13 years, but up to one-quarter of reported cases comprises the under-ﬁ  ves. Race and socio-economic status are not major risk fac-

tors, but there are increased rates of sexual abuse among children living with parents who are emotionally unavailable, psychiatrically disturbed, violent, or who abuse alcohol or drugs.
(9) Children from 
lower socio-economic groups are over-represented in child protec-tion samples, but in adult retrospective surveys there is a weaker link with economic status. Children who have been in substitute care are at higher risk.
Girls are more than twice as likely to be victimized. Boys are 
less likely to be reported or discovered to have been abused during their childhood. Compared with girls, boys are more likely to be older when ﬁ  rst victimized and to be abused by someone from 
outside the immediate family, and more likely to be abused by women or by offenders who are known to have abused other children. The risk of sexual abuse is almost doubled for children with a disability.
(10)
(b) Characteristics of abusers

(10)
Most abusers are male, but up to 10 per cent of children are abused by a female, though this ﬁ  gure is higher when the victim is male. 
Of abusers, 70 to 90 per cent are known to the child, with family members comprising between a third and a half of those who abuse girls, and between 10 and 20 per cent of abusers of boys.
Up to one-third of children are abused by a person who is under 
18 years of age. Y oung abusers  are, on average, 14 years old, while 
their victims are 7 years old and usually known to them.
(11) The 
abusers lack social skills and assertiveness, and show impulse-control problems, learning difﬁ  culties, and clinical depression. 
Their home environments are characterized by instability, family violence, and sexual problems in their parents. Parental loss or separation is common among adolescent abusers.Between 20 and 50 per cent of abusers have a history of child-

hood sexual abuse themselves. Physical abuse histories are even more common, together with deprivation and periods of substitute care in childhood. These characteristics are common among other offenders for non-sexual abuse offences, and thus do not explain the aetiological pathways through which some young people and adults develop a pathway of sexual attraction or desire to sexually assault a child. Marshall and Barbaree
(12) have drawn together psy-
chological, biological, and social factors into an integrated theory of aetiology.
Abusers typically deny sexual abuse allegations. Even measures 
of penile tumescence in response to childhood imagery are unlikely to discriminate a denying abuser from a falsely accused man. Some psychological features are common among abusers but are unlikely to be deﬁ  nitive, prior to any admission of guilt.
(13) The

(13) The 
demarcation between intrafamilial and extrafamilial abusers is less sharp than originally thought, and mixed abusers are relatively common.
(c) Family aspects
Up to half of all cases are abused by someone outside the family. In the majority of these extrafamilial cases the abuser is known to the child and in a position of trust, either providing care or supervi-sion, or involved in an educational or recreational activity with the child. Among within-family cases, the original stereotype-of a closed family with a controlling abusive father and mother who is collusive with her husband’s abuse of her child-has been demon-strated to be inaccurate. Although such a pattern may be seen, a variety of family styles of functioning occur. However, investiga-tors have found that families containing sexual abuse victims are less cohesive, more disorganized, and permit less healthy expres-sion of emotion than comparison families.
(14) These differences

(14) These differences 
may pre-date the onset of sexual abuse or be a consequence of its occurrence.
(9) Nonetheless, the observations are important for 
intervention purposes.
Support from non-abusive adult carers (usually mothers) in 
terms of belief, protection, and help for children to understand their victimization, is positively linked with the children’s response to their experience.
(15) This is important for assessment and inter-
vention purposes, because there is a signiﬁ  cant link between sexual 
abuse and markers of parent-child relationship difﬁ  culties, such as 
emotional unavailability, interparental conﬂ  ict, parental mental 
health, and substance abuse problems.
(d) Course and prognosis
A wide range of psychological sequelae in childhood and adult life are associated with prior childhood sexual abuse (Table 9.3.3.1).
(9,15)

(9,15)
However, these are linked with the effects of both the quality of the family environment at the time of abuse, and the nature of subse-quent life events.
(16) In particular, factors such as family disharmony 
and violence, existence of other forms of abuse and neglect, and parental mental health difﬁ  culties, in addition to subsequent events, 
such as losses through death or separation, combined with the child’s own method of coping with the abuse and ameliorative effects of positive school or social relationships, all contribute to outcome.
About one-third of children are symptom free. Approximately

About one-third of children are symptom free. Approximately 
10 per cent of children show worsening symptoms over time, including depression and post-traumatic symptoms. While effects on personality and social relationships can be disabling during development, other children are relatively unaffected.
(16,17)9.3.3 child abuse and neglect

SECTION 9  child and adolescent psychiatry 1734
Physical abuse
Physical abuse is the physical assault of a child by any person 
having custody, care, or charge of that child. It includes hitting, throwing, biting, inducing burns or scalds, poisoning, suffocating, and drowning.
(3) In the United States and United Kingdom physical 
chastisement of children is commonplace, leading to problems of deﬁ nition. In other parts of Europe and in some Eastern cultures 
physical chastisement is regarded as unacceptable. Legal deﬁ  nitions 
in the United States and Western Europe normally link physical acts to observable harm. However, for research and clinical pur-poses an endangerment-based deﬁ  nition is preferable, because of 
the widely different sequelae resulting from similar assaults.
(18)
Failure to prevent injury or suffering is preferably considered a manifestation of neglect. Other deﬁ  nition problems include the

(18)
Failure to prevent injury or suffering is preferably considered a manifestation of neglect. Other deﬁ  nition problems include the 
frequency or repetitiveness of the acts, their severity, and whether intent to harm should be included. In addition, developmental factors affect the recognition of abuse and possibly its deﬁ  nition 
also—a smack to the head of an 8-year-old, although unacceptable, will have signiﬁ  cantly different consequences from that to an 
8-month-old.
The distinction between accidental injury, non-accidental injury, 
and speciﬁ  c medical diseases is sometimes straightforward (e.g. 
particular types of fractures, burns, or bruising) but difﬁ  cult 
diagnostic dilemmas do occur. It is important to resolve these dilemmas so that the way forward for psychiatric assessment and 
treatment can be clariﬁ  ed.
(19)
The ‘battered child syndrome’ refers to young children with mul-

(19)
tiple bruises, skeletal injuries, and head injuries, often accompanied by neglect, malnutrition, and fearfulness, whose parents deny responsibility.
(20)
Diagnosis and recognition
Physical abuse is detected through the observation of physical injuries without an alternative non-abusive explanation.
(19)Less commonly, a direct account comes from a child or a witness, or through confession by a parent or carer. Usually, the diagnosis is based upon a discrepancy between the physical ﬁ  ndings and the 
history provided. The history may be insufﬁ  cient or simply improb-
able. When an explanation is forthcoming, trigger events or devel-opmental challenges are common—for example, persistent crying in infancy, problems of toileting or feeding among toddlers, or issues of discipline in later childhood. In adolescents, conﬂ  ict

surrounding independence may coincide with parental midlife crises. Not all physical abuse can be related to loss of control, how-ever, and the assessor has to consider planned or even sadistic activities, such as scalding, burning, or torture.
There may have been previous episodes of similar or lesser 
concern, for which adequate explanations were unavailable at the time. Delay in presenting the child for medical attention is not a reliable diagnostic feature; neither is the apparent absence of paren-
tal concern nor their unreasonable behaviour at presentation.
Aetiology and background factors
(a) Child characteristics
Physical abuse occurs at all ages, although biological sequelae are 
more severe in infancy. There is no association with ethnic group, but a strong one with low socio-economic status among the under-ﬁ ves, becoming weaker throughout childhood and disappearing by 
adolescence.
(21) Children with developmental disabilities have a

(21) Children with developmental disabilities have a 
raised risk.(10) Associations with low birth weight, prematurity, or 
physical ill health disappear once parental and social variables are controlled for. Boys under 5 years of age are more likely to be abused, whereas girls are at greater risk in childhood overall.
(b) Abuser characteristics
Y oung maternal age at the time of the child’s birth is linked with abuse, but generally the effect of age is overshadowed by low socio-economic status and high social stress.
(21) Physical abusers of

(21) Physical abusers of 
young children are likely to be female, but male abusers predomi-nate during adolescence. They are more likely to be single parents and to have large numbers of closely spaced children. Their educa-tional level, but not necessarily their intelligence, is lower; they are, however, more likely to be unemployed. Most physical abuse is perpetrated by parents, but others who adopt a caretaking role become increasingly signiﬁ  cant in the abuse of older children.
Abusive parents are more likely to have had a childhood history 
of abuse themselves. However, regarded prospectively, 70 per cent of abused children do not abuse their own children.
(22) Non-

(22) Non-
repeaters are more likely to have enjoyed social support from a partner, had a positive relationship with an adult during childhood, and to have received psychological help during adolescence. In addition, they have a more balanced and coherent perspective about their childhood experiences than those who show intergenera-tional continuity of parenting problems. The quality of attachment relationships between parents and children shows continuity, rather than the speciﬁ  c type of abuse. Hence, physically abused 
children have an increased risk of perpetrating both physical and sexual abuse when they become parents themselves.
Frank psychiatric disorder is relatively infrequent among abus-
ers, but studies of physical abuse fatalities underline their impor-tance in a minority of cases.

(23) Personality difﬁ  culties and disorders 
are more common, however. Hostile adults with poor impulse control, low self-esteem, antisocial and aggressive personalities, Table 9.3.3.1  Impairments and problems associated with childhood 
sexual abuse
Childhood impairment Adult impairment
Affective symptoms Fears
PTSD
DepressionAnxiety
PTSD
Behaviour problems Conduct disorder
Sexualized behaviourSelf-destructiveness
HyperactivityAggressive conduct
Self-destructiveness
Alcohol/substance abuse
Cognitive functioning Educational problems
Language difﬁ  cultiesEducational 
 underachievement
Personality and social 
 adjustmentSelf-esteem
AttachmentPeer relationshipsPregnancy under 19 years
Sexual aggression
Prostitution
Parenting problemsSomatization
Revictimization
Sexual problems

1735
with accompanying mood disorder are more likely to abuse. 
These abusers have disrupted social relationships and inadequate coping responses in a wide range of domains. They are frequently socially isolated, alienated, and have disharmonious relationships with neighbours and relatives. For these adults, potentially protective supportive relationships with friends and relatives are inhibited.
(3, 21)
Abusive parents have maladaptive ideas about their children.

(3, 21)
Abusive parents have maladaptive ideas about their children. 
They tend to have high expectations for their children’s develop-ment and behaviour, perceiving it to be deviant when objectively it is not. They are more likely to believe in the appropriateness of strict physical discipline, and to hold negative views and percep-tions about their children. They show limited attention to their children, less positive affect, and respond with aversion, anger, or irritation to their children’s bids for care or attention, as well as to their positive behaviours, when compared with non-maltreating parents. Physically, abusers show heightened arousal to both child stimuli and non-child-related stressors.
(3, 21)

(3, 21)
Families in which physical abuse occurs are more likely to support mutually abusive coercive communications and interactions than controls. Partner abuse and domestic violence is relatively more common, combined with pervasive hostility and decreased cohe-sion. Discussion, positive displays of affection, and encouragement of prosocial behaviours are less common than in non-maltreating families.
(3, 21)
The quality of attachment between child and parent is signiﬁ  -
cantly linked with physical abuse, especially when combined with high levels of social stress, low socio-economic status, and negative parental family attitudes and behaviours. Although infant temper-ament can be associated with maltreatment it probably only does so if combined with other risk factors, such as parent–child attach-ment problems, parental attitudes, and family difﬁ  culties of the

sort described above. Clinicians have long observed that individual children can be perceived negatively by parents, without objective evidence, particularly if the child represents a particular issue or problem for the parent.
Some physically abused children have neurological and other phys-ical sequelae as a result of their injuries.
(4) Educational difﬁ  culties

(4) Educational difﬁ  culties 
are consistently found on follow-up. The children are less attentive to social cues and less skilful at managing personal problems and more likely to attribute a hostile motivation to their peers, compared with non-abused children, at the age of 5. Their capacity for empathic concern with the everyday problems of their peers becomes blunted. Not surprisingly therefore, chronic oppositional and aggressive behaviour is the most consistently documented childhood outcome. These children range from the socially with-drawn and avoidant, to those who demonstrate fear, anger, and aggression. These features are linked both to the physical abuse and the family context of pervasive aggression and conﬂ  ict.
(3)
The children’s attachments to their caretakers are anxious and

(3)
The children’s attachments to their caretakers are anxious and 
insecure. Children view themselves negatively, and show increased rates of both depression and anxiety throughout childhood. Long-term exposure results in a constellation of reactions characterized by pervasive denial by the child, an apparent repression or dissocia-tion of memories, relative indifference to pain or distress, episodes of rage directed towards self or others, and an unremitting sadness. 
Male victims may develop a characteristic hypervigilance.
(21)
The major health consequences of physical abuse in childhood 
have become clariﬁ  ed.(3) The causal connection between physical 
abuse and later psychological and physical health problems is

(21)
abuse and later psychological and physical health problems is 
underlined through clear links between early age of onset, and severity of maltreatment and subsequent severity of psychological and physical ill effects in teenage and adult years. Further, physical abuse cases embedded within violent families and associated with accompanying neglect have relatively worse outcomes, psycho-socially and in physical health. Approximately 20 to 30 per cent of physically abused children develop conduct problems in teenage years, starting earlier and displaying more violence than their non-
abused counterparts. They are at increased risk of running away

abused counterparts. They are at increased risk of running away 
from home, and are overrepresented among young homeless chil-dren in inner cities. Childhood physical abuse is associated with subsequent substance abuse problems, self-destructive behaviour and suicidality, depression, teenage pregnancy and poor physical health outcomes. Genetic factors mediate the association between physical abuse and later antisocial behaviour and, probably, affec-tive disorder too.
(3)
Child neglect
Neglect refers to the underprovision of the child’s basic needs, both 
physical and psychological. Most cases comprise omissions of care by parents and others in the parental role. However, institutional neglect also occurs, mainly in the form of collective caretaking failure—for example, residential children’s homes in the United Kingdom, orphanages and nurseries in Eastern Europe, and neglect of care by educational establishments.
(3)

(3)
Deﬁ nition problems include whether neglect should include 
the apparent impact on the child and/or the degree to which it was 
intended.(3) There are cultural variations in what might be per-
ceived as neglect. The practice of putting young children into sepa-
rate bedrooms, while considered normal practice in much of 
Western Europe, would be considered frankly neglectful in some Eastern cultures.
Notwithstanding these deﬁ  nition problems, four main types can 
be identified: physical, supervisory, cognitive, and emotional 
neglect. Neglect can occur ﬁ  rst during the prenatal period, for 
example through maternal substance abuse, and may be observed 
throughout childhood. Physical  neglect includes inadequate nutri-
tion, clothing, shelter, but also exclusion and abandonment. This is the most common form of neglect reported to welfare agencies in North America, Australia and Western  Europe. Supervisory

involves inadequate parental overview, relative to the child’s needs, for developmental needs of the child, but also employing unsafe alternative carers, and failure to use available health care. Emotional  neglect includes insufﬁ  cient parental affection, and 
inattention to the child’s cues, which has been termed ‘psychologi-cal unavailability’ .
(24) Cognitive  is insufﬁ  cient parental responsive-
ness, attention and speech, but also denying access to education opportunities.
Diagnosis and presentation
Although most reported cases involve younger children, neglect occurs at all ages. Many cases are followed for years before being 9.3.3 child abuse and neglect

SECTION 9  child and adolescent psychiatry 1736
ﬁ nally identiﬁ  ed by professionals. Non-organic failure to thrive can 
precipitate earlier recognition. Otherwise neighbours, relatives, or school teachers report the child’s plight to protection agencies, by which time the effects are severe and neglectful caretaking entrenched. Recognition may also come about through the child’s presentation with developmental delay, language problems, school non-attendance, inadequate medical or dental care, or with signiﬁ  -
cant psychological difﬁ  culties. Conclusions about neglect need to 
be linked with the individual’s developmental needs. Additionally neglect must be distinguished from the effects of poverty. Conclusions are assisted by using multiple sources of information; from the children themselves, caregivers, reviewing longitudinal 
case records, direct observation and standardized measures.
(3)
(a) Characteristics of neglectful parents

(3)
Neglectful parents are likely to be poor, have multiple difﬁ  culties, 
and display what has been described as the apathy-futility syndrome. Parents show immature personality characteristics, with low self-esteem, impulsivity, and an inability to plan or demonstrate choice in such important areas as adult partners, having children, or employment. Neglectful parents frequently hold inaccurate or unre-alistic expectations about their children’s development or behaviour. Neglect may derive from parental psychiatric illness such as schizo-phrenia, depression, or drug or alcohol abuse.
(b) Characteristics of neglected children

Neglected infants have anxious, disorganized attachments with their caretakers. Later in childhood they are more aggressive than comparison children, though less so than physically abused chil-dren. Neglected toddlers show non-compliance and become easily frustrated, later developing low self-esteem and self-assertiveness and showing less ﬂ  exibility or self-control. Both in preschool and 
school they lack persistence and enthusiasm, and become socially isolated.
Child neglect is normally embedded within broader family insularity, lack of cognitive stimulation, affection or emotional nurturing between its members, and signiﬁ  cant household disorganization.

Child neglect is normally embedded within broader family insularity, lack of cognitive stimulation, affection or emotional nurturing between its members, and signiﬁ  cant household disorganization. 
Neglectful parents are likely to be unresponsive to both their infants and older children, showing a paucity of prosocial positive behaviours, less interactions and stimulation, and more negative behaviours than controls. Even though there is a strong link with poverty, parents who neglect children stand out among their equally materially impoverished neighbours.
The seeds for the neglected child’s long-term difﬁ  culties with social 
interaction, relationships, and educational progress can be observed in infancy. Neglected children tend towards passiveness and helplessness under stress. They show signiﬁ  cant developmental 
delays, especially language problems, attention-seeking behaviour, and superﬁ  cial displays of affection, as well as conduct problems,

delays, especially language problems, attention-seeking behaviour, and superﬁ  cial displays of affection, as well as conduct problems, 
persistent deﬁ  ance, and hostile behaviour. Studies of children who 
as infants were subjected to psychologically unavailable caretaking reveal persisting difficulties with anger, non-compliance, low frustration tolerance, little enthusiasm or persistence for tasks, poor impulse control, relative rigidity, and lack of creativity. Similar negative developmental outcomes have been reported to occur following non-organic failure to thrive in infancy, especially where 
combined with physical neglect, leading to long-term cognitive delay and poor educational attainment. Children who as infants experienced psychologically unavailable parenting do even worse than physically abused children, showing a greater number of emotional problems, inattention, social withdrawal, and unpopu-larity with other children.
(24)
Psychological maltreatment

(24)
Emotional abuse (better termed ‘psychological maltreatment’) 
refers to those interactions with children that have the potential to damage the child psychologically, given his or her particular developmental needs.
(3) Four broad groupings of acts are described: 
the need for psychological safety and security; for acceptance and positive regard; for age appropriate autonomy, and sufﬁ  cient 
opportunities to explore environment and extra familial relation-ships. Included within psychological safety  are exposure to 
domestic violence, threats of injury, suicide or abandonment, and discipline through intimidation. Within acceptance and self-
esteem  are verbal and non-verbal negativity, active rejection, 
ridiculing, inappropriate expectations and undermining. Age 
appropriate autonomy  includes both inappropriate responsibility

appropriate autonomy  includes both inappropriate responsibility 
giving and prohibiting age appropriate socialization and placing a child in a reversed parental role. Restriction  includes restrictive 
conﬁ  nement and isolation.
Psychological maltreatment may be direct toward the child, 
or operate indirectly, for example through the child witnessing 
domestic violence, or observing parental involvement in antisocial 
activities. It may occur in institutional settings as well as within 
families. The overlap with neglect is evident from the list of acts of 
omission and commission listed above.
Recognition may occur when other kinds of maltreatment are dis-covered, or when domestic violence is revealed. It may also occur

Recognition may occur when other kinds of maltreatment are dis-covered, or when domestic violence is revealed. It may also occur 
when a child is noted to be living with, and/or providing care for a parent with mental or physical illness, personality disorder or sub-stance abuse. Sometimes recognition follows a child’s referral to developmental or mental health clinic, or through the reported observations of neighbours or professionals (e.g. teachers, police). Diagnosis requires detailed history, with examples, direct observa-tions of parent-child interactions, and interviews with older children. Standardized data gathering schemas may assist diagnosis.

Reports of emotional abuse in children become more frequent throughout childhood into adolescence. Reported cases are more likely to be linked with lower socio-economic status. There is no particular link with racial or ethnic groups. Psychological maltreat-ment is frequently integral to other forms of maltreatment and so distinguishing different aetiological factors and consequences is complex.
Although not systematically studied, this probably varies according to the mixture of subtypes present, and whether any other kinds of abuse or neglect coexist.

1737
Psychological maltreatment in infancy has a very poor outlook (see 
discussion of neglect). Much less is known about the outcome of different mixtures of psychological maltreatment identiﬁ  ed during 
childhood and adolescence. There are indications that the degree and extent of psychological maltreatment is a better predictor of case outcome than the extent of any coexisting physical or sexual abuse, thus underlining its importance to the developing person’s mental health.
Fabricated or induced illness 
(Munchausen syndrome by proxy)
Deﬁ nition and key elements
Fabricated or induced illness (FII) is where a parent or carer feigns 
an impression or induces a state of ill health in a child whom they are looking after. The key elements are parental falsiﬁ  cation or

an impression or induces a state of ill health in a child whom they are looking after. The key elements are parental falsiﬁ  cation or 
deceit, and a triangular interaction between parent, child, and health professional, in which the doctor is misled by the parent, some parental need is met, and the child harmed (directly or indirectly). The harm occurs through: verbal fabrication of symptoms/signs; falsiﬁ  cation of reports or specimens; or through inducing ill health 
(either actively or by withholding essential substances).
(25)
Diagnosis
The presentation can be in any bodily system, but common forms are fabricated epilepsy, non-accidental poisoning, apparent life-threatening events in infancy (either directly induced suffocation, or fabricated), or multi-system disorders (e.g. gastrointestinal and renal problems).
The diagnosis of fabrication is almost always undertaken by

The diagnosis of fabrication is almost always undertaken by 
paediatricians, whose awareness of the possibility of fabricated signs or symptoms is now much greater and leads to an earlier diagnosis than when ﬁ  rst described by Meadow.
(26)
There are several elements to the phenomenon:
1 the harm caused to the child through fabrication;2 the impact on the child’s development, both physically and 
emotionally;
3 the psychological status of the fabricator.
Psychological services are especially involved in (2) and 
(3)—assessing the child’s developmental status, and considering the mental state of the fabricator and assessing family dynamics. Differentially, factitious illness by proxy needs to be distinguished from parental overanxiety or exaggeration, or frank malingering, though sometimes FII contains elements of all these.
(25)

(25)
The annual incidence among children in the United Kingdom has been calculated to be 0.5 per 100 000, but for those under 1 year it is 2.8 per 100 000.
The majority of children are under 5 years of age, with boys and girls equally represented. Affected infants are likely to have feeding problems; withdrawal and hyperactivity are seen in school-age children, whereas adolescents may develop somatization themselves. Up to three-quarters of the children show evidence of 
other fabrications, or of physical abuse and neglect.
Most fabricators are female—79 per cent of whom have a somati-zation disorder themselves and half have a personality disorder, particularly so among fabricators who induce illness. Most abusers deny responsibility, at least initially.
(c) Family characteristics

Unusually, families are often intact, though 40 per cent have serious marital problems. Child-parent attachment difﬁ  culties are com-
mon, and other siblings in the family may be affected. Typically, fathers are not involved in family life.
Affected children may be damaged by the abuse itself, while mor-tality is between 5 and 10 per cent. About 20 per cent are reabused, though not necessarily in the same way as the original FII. Emotional harm, conduct problems, and educational difﬁ  culties 
occur in half the children on follow-up.
Prevention of maltreatment
Reducing the incidence and recurrence of child maltreatment are crucial initiatives, because of the resultant ill effects
(27) and

(27) and 
difficulty in instituting effective treatments, quite apart from the humanitarian prerogative. Family support—and education concerning parenting, child development, and the management of problems—has a positive impact on parental attitudes and knowl-edge as well as on observed behaviour. Significant effects on children’s behaviour, cognitive outcome, and child maltreatment rates are less clear. Preventive efforts have more impact upon phys-ical abuse than on neglect.
(28)
Brief interventions are beneﬁ  cial for low-risk parents, whereas

(28)
Brief interventions are beneﬁ  cial for low-risk parents, whereas 
more intensive approaches are needed for higher risk groups. High-risk groups include deprived, impoverished parents, young mothers, and those with a personal history of childhood abuse themselves. However, for a prevention approach to be effective it must be personalized to the needs of the individual families and include outreach components for the most negative and hard to access parents.
(28) Including males, whether resident or occasional 
visitors, is crucial to maintaining and sustaining improvements in parenting and child care. Equally, effective programmes are more likely to be valued by the parents themselves, underlining the importance of matching the skills of staff and the contents of programmes with the families’ specific needs.
(29,30) Similarly,

(29,30) Similarly, 
programmes must be culturally sensitive if they are to be effective and accepted by parents. Interventions are most effective when they impact upon a broad network of inﬂ  uences and relationships, 
ranging from those of the immediate family to broader neighbour-hood and social inﬂ  uences on children’s welfare.
(3) Furthermore, 
primary, secondary and tertiary prevention approaches need to be integrated and carefully planned within each area.
(31)
Sexual abuse prevention is probably ineffective when aimed at 
enhancing children’s capacity to protect themselves.(28) On the 
other hand, programmes which include parents (and increase their capacity to keep their children safe) and incorporate antibullying tactics are much more likely to be effective, although this probably stems from increasing disclosure of early sexually abusive actions rather than primary prevention.
(28) Additionally, broader social 9.3.3 child abuse and neglect

SECTION 9  child and adolescent psychiatry 1738
initiatives to reduce child sexual abuse within schools and institu-
tions are essential to a comprehensive area strategy.(27, 31)
Intervention and psychological treatment
Treatments
Psychological treatments have been developed for different types of maltreatment, notwithstanding contemporary appreciation that co-occurrence of types of maltreatment is common place. Effective treatments for physical and sexual abuse are reasonably well established.
Interventions with empirical support are principally behavioural, 
and cognitive behavioural ones.
(3) These are normally structured 
and emphasize skill building to overcome emotional distress and behavioural disturbance in children and parents. Trauma-focussed, cognitive behavioural therapies are signiﬁ  cantly superior to family

and general therapeutic treatments for both physical and sexual abuse. These treatments combine psycho-education, exposure therapy, cognitive procedures and restructuring as well as behav ioural 
management. Children are also assisted with emotional recogni-tion and regulation and attention to maladaptive ideas. Other empirically supported interventions include child parent psycho-therapy (blending psychodynamic and cognitive behavioural components).
Psychological treatments in neglect have concentrated on 
improving parenting skills and sensitivity through direct encour-agement of positive interactions in feeding, play, general care, 
combined with individual therapy for parents themselves.
(3)
Parallel psychiatric treatment of parental mental health problems,

(3)
Parallel psychiatric treatment of parental mental health problems, 
such as depression or substance abuse is also important, although there is debate about whether such treatments should precede or be delivered subsequent to treatments focussed on parenting. There has been some support for therapeutic day treatment programmes and multisystemic therapy for neglect.
Psychiatric interventions for psychological maltreatment have 
not been subject to empirical evaluation thus far. In the meantime it seems reasonable to focus on improving sensitivity and respon-siveness within parent child relationships (through direct work and feedback), together with family based work, and individual work with parents who have been subject to deprived or abusive backgrounds themselves.
Treatments for FII are sparse, but combinations of treatments

Treatments for FII are sparse, but combinations of treatments 
for neglect and psychological maltreatment, combined with behav-ioural management of somatization appears promising.
(3)
(a) Guiding principles(3, 32)
The ﬁ  rst priority is to establish the child’s safety  and/or freedom 
from neglect. This may require separation of child and abuser. Those cases involving neglect or psychological maltreatment may be managed through veriﬁ  able agreement, and providing services 
designed to promote the child’s welfare within the family. Interdisciplinary planning and coordination will be essential in order to achieve this.
Interventions must be focused primarily on the child’s welfare ,
rather than other objectives such as adult treatment or family preservation. Interventions should also focus on the child’s physi-
cal and emotional safety , and be developmentally focused , while simultaneously tackling parenting problems . A developmental

cal and emotional safety , and be developmentally focused , while simultaneously tackling parenting problems . A developmental 
focus involves adapting treatments to a child’s age and develop-mental status, and taking into account any developmental impair-ment. Additionally, it is essential that treatment approaches comprehensively address those developmental processes affected by maltreatment, i.e. affect regulation, attachment, the evolving self system, and peer relationships.
(5)
Approaches to parenting problems range from interventions 
with parents individually, those focused speciﬁ  cally on parent child 
dyads, through to more broadly based social support services, including day attendance at family centres designed to improve parenting care, the use of family support workers, harnessing neighbourhood supports and other parents prepared to assist new parents at risk, and parenting classes. Services to improve family conﬂ  ict resolution and parental management of hostility and

aggression may also be needed for a comprehensive approach to tackling parenting problems. Parents with mental health problems need to be psychiatrically evaluated to see whether treatment could assist overall case management. Sexually abusive behaviour or physical violence perpetrated by adults may be amenable to psychi-
atric intervention. Persistently dangerous abusers need to be 
identiﬁ  ed and child safety assured.
Further, interventions should speciﬁ  cally address the child’s 
experience  of maltreatment and any moral or legal dimensions to 
this. Interventions should not focus solely on maltreatment itself, but equally address any general mental health issues . They should 
also aim to prevent future difﬁ  culties  as well as addressing current 
problems. Supportive and nonabusive parents and carers  should 
be part of the intervention and incorporated into treatment plans. Obtaining parental acknowledgement and recognition  of their

be part of the intervention and incorporated into treatment plans. Obtaining parental acknowledgement and recognition  of their 
part in maltreatment is an important part of successful interven-tions. Parental acknowledgement may be achieved through educa-tion and discussion, and through treatment approaches designed to alter hostile or neglectful views and attributions held by parents. First choice interventions should be those with the highest level of empirical support . Generally, interventions should involve school 
and local networks  of child professionals in a systemic fashion. A 
systemic perspective is helpful with respect to all families. Sensitive working across disciplinary boundaries requires knowledge of local
family justice system and child protection working practices .
(b) Case planning
When deciding what to do in the individual case, treatment

When deciding what to do in the individual case, treatment 
may have to address several aspects of abuse and neglect, because co-occurrence of maltreatment type is common. Safety is of para-mount consideration. There is little value in starting treatment if the child remains unsafe. This will require multidisciplinary or multiagency co-operation in order to develop a comprehensive plan for child and family. Even where intensive treatments are unavailable, psycho-educational approaches are helpful for all abused children. In reality, most maltreated children receive no sys-tematic therapeutic intervention.
The majority of treatment approaches combine intervention for

The majority of treatment approaches combine intervention for 
the child with adult treatment and often family based work. Supportive work with non-abusive carers is of proven value. In planning this, however, it must be remembered that failure to protect a child is harmful and dangerous for the child’s future too. 
In addition, in one family there may be more than one maltreating 
carer, e.g. abuse by one adult carer and neglect by another.

1739
Effectiveness of intervention is gauged through several dimen-
sions. For example, child safety, improved carer availability and sensitivity for the child, whether the child has overcome effects of trauma, psychological symptom reduction, improved peer relationships, speech and language catch up and educational prog-ress. Improvements in family functioning which are sensitive to interventions include; reduced conﬂ  ict and violence, improved 
communication and emotional expression, changes to disturbed attachment patterns and improved child to parent attachment, and greater warmth in parent/child relationships. In addition, effective-ness may be gauged through target mental health objectives for individual carers, e.g. reduction in parental depression or improve-ments in anger management.
Developmental considerations will also contribute to evaluation

Developmental considerations will also contribute to evaluation 
of effectiveness. For example, a shorter timescale is appropriate for younger children in view of their developmental needs; and greater than average improvement in parenting may be needed for children with impairments or disabilities.
Risk management is a central issue for mental health practitio-
ners when providing interventions in maltreatment cases, and underlines the need for systemic awareness and well-developed inter disciplinary practice. Risk factors for occurrence are reviewed 
elsewhere.
(3) Recurrence risk has been the focus of systematic 
review(33), and narrative overview, using an eco-developmental 
perspective and identifying risk elevating as well as lowering fac-tors.
(34) Nonetheless, multiplicity of relevant factors as well as

(34) Nonetheless, multiplicity of relevant factors as well as 
complexity of transactions in individual cases render actuarial approaches to risk management an unrealistic aspiration at this point. In its place, an approach that has been characterized as structured professional judgment appears the most appropri-ate.
(35) Key risk elevating factors for recurrence include: domestic 
violence, child neglect, cases where there had been previous mal-treatment, and parents with mental health disorders. A structured approach to risk management entails an approach to data gather-ing, diagnostic formulation and subsequent decision making that rests explicitly on available evidence about risk factors for recurrence.
(34)
(c) Ethical and legal considerations

(34)
Decisions as to whether to share sensitive information with other professionals will be guided by child welfare and safety consider-ations, which are paramount, and override adult consent withheld. Sometimes children request conﬁ  dentiality, in situations where 
their safety is potentially compromized. Normally, explaining to children why information must be shared, and involving them enables their trust to be maintained even where there is initial disagreement.
Generally, patient information will need to be shared during 
multidisciplinary planning meetings, but agreement can usually be made to respect conﬁ  dentiality, except to the degree necessary to 
assure child safety. Many cases will involve family justice systems, which normally require overview of progress. Practitioners will need to provide reports for planning meetings and family courts, in order to contribute to safe care.
(d) Long term

Mental health effects may present at different points in the life course, particularly at key times of developmental change, e.g. at a ﬁ rst romantic relationship, or when becoming a parent. If possible, 
such possible future difﬁ  culties should be noted in a person’s medical record, to facilitate future intervention. As part of an area’s 
comprehensive prevention approach, new parents with a history of childhood maltreatment should be offered extra support, as they are a vulnerable group for parenting problems (although it is important to stress that discontinuity of parenting problems is more common than continuity).
Web sites
California Evidence-based Clearinghouse for Child Welfare. 
http://www.cachildwelfareclearinghouse.org/
Every Child Matters. http://www.everychildmatters.gov.uk/
International Society for the Prevention of Child Abuse and Neglect. http://
www.ispcan.org/
National Society for the Prevention of Cruelty to Children. http://www.

nspcc.org.uk/Inform/informhub_Wda4993.html
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interactions within incest and non-incest families. American Journal of 
Psychiatry ,148, 46–9.

15. Jones, D.P .H., and Ramchandani, P . (1998). Child sexual 
abuse—informing practice from research . Radcliffe Medical Press, 
Oxford.9.3.3 child abuse and neglect

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16. Glaser, D. (2008). Child sexual abuse. In Rutter’s child and adolescent 
psychiatry (5th edn) (ed M. Rutter, D. Bishop, D. Pine, et al.). Blackwell, 
Oxford.
17. Rind, B., Tromovitch, P ., and Bauserman, R. (1998). A meta-analytic 
examination of assumed properties of child sexual abuse using college samples. Psychological Bulletin ,124, 22–53.
18. National Research Council (1993). Scope of the problem. In 
Understanding child abuse and neglect , pp. 78–105. National Academy 
19. Johnson, C. (2002). Physical abuse: accidental versus intentional 
trauma in children. In The APSAC handbook on child maltreatment 
(ed. J. Myers, L. Berliner, J. Briere, et al.), pp. 249–68. Sage, 
London.
20. Kempe, C.H., Silverman, F.N., Steele, B.F., et al. (1962). The battered 
child syndrome. Journal of the American Medical Association ,181,
17–24.
21. Kolko, D. (2002). Child physical abuse. In The APSAC handbook on

17–24.
21. Kolko, D. (2002). Child physical abuse. In The APSAC handbook on 
child maltreatment (ed. J. Myers, L. Berliner, J. Briere, et al.), pp. 21–54. 
22. Kaufman, J., and Zigler, E. (1989). The intergenerational transmission 
of child abuse. In Child maltreatment; theory and research on the 
theory and causes of child abuse and neglect (ed. D. Cicchetti, and 
V . Carlson), pp. 129–50. Cambridge University Press, 
23. Jones, D.P .H., and Lynch, M.A. (1998). Diagnosing and responding to 
serious child abuse. British Medical Journal ,317, 484–5.
24. Erickson, M., and Egeland, B. (2002). Child neglect. In The APSAC 
handbook on child maltreatment (ed. J. Myers, L. Berliner, J. Briere, 
et al.), pp. 3–20. Sage, London.
25. Jones, D.P .H., and Bools, C.N. (1999). Factitious illness by proxy. In 
Recent advances in paediatrics (ed. T. David), pp. 57–71. Churchill 

26. Meadow, S.R. (1997). Munchausen’s syndrome by proxy: a hinterland 
of child abuse. Lancet ,ii, 232–5.
27. Daro, D., and Cohn Donnelly, A. (2002). Child abuse prevention: 
accomplishments and challenges. In The APSAC handbook on child 
maltreatment (ed. J. Myers, L. Berliner, J. Briere, et al.), pp. 431–48. 
28. Wolfe, D., Reppucci, N., and Hart, S. (1995). Child abuse prevention: 
knowledge and priorities. Journal of Clinical Child Psychology ,24
(Supplement), 5–22.
29. Cox, A. (1998). Preventing child abuse: a review of community based 
projects. II: Issues arising from reviews and future directions. Child
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status quo is not an option. Child Abuse and Neglect, 29(3), 
209–13.

209–13.
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Primary prevention of child physical abuse and neglect: a critical review—part I. Journal of Child Psychology and Psychiatry, 
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835–56.
32. Saunders, B.E., Berliner, L., Hanson, R.F. (eds.) (2004). Child Physical 
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recurrence of maltreatment: a systematic review. Archives of Disease in 
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for violence risk assessment: Clinical and research applications. Criminal Justice and Behavior ,29(5), 617–58.9.3.4 The relationship between 
physical and mental health in children and adolescents
The link between physical and psychological disorder in children 
and adolescents is well established. Children with chronic illness are at increased risk of emotional and behavioural disorders. In addition, repeated presentations with physical symptoms may represent underlying psychological distress or psychiatric disorder.
Because of the inextricable links between young people and the

Because of the inextricable links between young people and the 
family in which they live, it is inappropriate to consider symptoms in an index child in isolation. The effects of symptomatology on family functioning, parent, and sibling relationships should be considered. This may have important aetiological and prognostic signiﬁ  cance.
Associations between physical and 
psychological symptoms
There are various ways in which physical and psychological disor-
ders are related; these are summarized in Table 9.3.4.1.
In this chapter we shall consider the following:
◆ The psychiatric consequences of physical illness
◆ Helping the dying child and his or her family
◆ The effects of psychiatric disorder on the course and outcome of physical illness
◆ Aspects of assessment and treatment intervention
Table 9.3.4.1  Associations between physical and psychological 
symptoms
Nature of association Examples
Psychiatric consequences of

symptoms
Psychiatric consequences of 
physical illness and treatmentOrganic : acute confusional state, 
psychosis induced by brain disorder
Functional : adjustment disorder after 
diagnosis of diabetes, speciﬁ  c needle 
phobia in young child with cancer receiving chemotherapy
Effects of psychiatric disorder on 
physical illnessDepression delaying the mobilization 
of a child following partial limb 
amputation after severe meningococcal disease, oppositional-deﬁ  ant disorder 
affecting treatment adherence in 
diabetes
Physical complications of 
psychiatric problems e.g. deliberate 
self-harm, substance abuseLiver failure following paracetamol 
overdose
Psychiatric disorders or 
psychological distress presenting with physical symptomsAches and pains in school age 
children, reduced physical well-being 
in adolescent depression, somatoform

overdose
in adolescent depression, somatoform 
pain disorder, dissociative disorder

1741
◆ Somatization and somatoform disorders, with a particular focus 
on recurrent abdominal pain, dissociative/conversion disorder, and chronic fatigue syndrome
Psychiatric aspects of chronic 
physical illness
Chronic physical illness and the risk of 
psychiatric disorder
Chronic physical illness in children, deﬁ  ned as disorders that last 
at least 1 year and are associated with persistent or recurrent hand-icap, affects about 4 per cent of children in Western countries.
(1)
This encompasses a broad spectrum of disorders including more common problems such as eczema, asthma, diabetes, epilepsy, and less prevalent conditions such as cystic ﬁ  brosis and cancer. Many 
children successfully adapt to living with a chronic illness, but it can be associated with a number of different types of stresses for children and their families.
The stress of chronic illness may operate at several levels. In addi-

tion to the presence of the illness itself, diagnostic and treatment procedures may be painful or have undesirable side-effects—changes in physical appearance such as alopecia, scars, and obesity may lead to difﬁ  culties in peer relationships. The demands of treat-
ment such as dietary restrictions in diabetes may be difﬁ  cult. The 
illness, together with hospital attendance for treatment, may lead to a considerable interruption to schooling as well as a reduced ability to participate in leisure activities and socialize with peers.
Although the majority of children and families successfully adapt 
to these stresses, children with chronic physical illness have a slightly increased risk for the development of associated psychiatric disorders. Speciﬁ  c factors related to the child and the illness have been shown 
to contribute to the likelihood of developing psychiatric distur-

bance and to inﬂ  uence the nature of the psychiatric disorder that 
develops (Table 9.3.4.2).
(2)
(a) Nature of the physical disorder
Much of the increased prevalence of psychiatric disorder in chil-
dren with chronic physical illness is accounted for by those with disorders affecting the brain, especially when epilepsy is involved.
(3)
They have a three-fold increased risk of psychiatric disorder over general population rates. The risk in young people with a chronic physical illness that does not involve the brain is considerably lower and only slightly increased over general population expectations.
(3)

(3)
The excess of psychopathology in children with brain anomalies may be attributable to the direct effects of organic pathology on behaviour, or may be mediated by the greater physical disability that frequently accompanies brain damage. Associated intellectual impairment may also be an important contributory factor.Whilst this dichotomy between disorders involving and not 
involving the brain is useful, there is little speciﬁ  city in the behav-
ioural pattern that may be attributable to intracerebral pathology. As a possible exception, children with brain dysfunction such as epilepsy or cerebral palsy may be more likely to exhibit externaliz-ing disorders such as hyperactivity.
(3) Psychiatric disorders in this 
group of children may be persistent, with 70 per cent still experi-encing difﬁ  culties at 4-year follow-up. Overactivity, restlessness, 
and inattention are the best predictors of persistence.
For conditions not affecting the brain, the development of psy-

chiatric disorder seems most likely to be linked with the accumula-tion of generic stress factors and family changes common to living with a chronic illness. These include life stresses such as hospital-ization and daily difﬁ  culties such as speciﬁ  c dietary requirements 
and disruption of family routines.
(4) A broad spectrum of psychi-
atric presentations are associated and these are not speciﬁ  c to the 
nature of the underlying disease processes. Children with non-neurological physical illnesses are more prone to developing emo-tional symptoms and eating anomalies as opposed to antisocial behaviour. Eating anomalies may arise from an emphasis on diet and a concern about poor appetite in the families of many children with chronic illnesses. Maternal anxiety may focus on feeding, especially in preschool children. The speciﬁ  city of the relationship

with emotional disorders is of interest. Physical illness in the child can generate family and social stresses and changes that are known risk factors for the development of emotional disorders in children. This includes mood disorders in parents and overinvolved and overprotective parenting.
(2)
(b) Stage of the illness
Disorder at the time of initial diagnosis is not uncommon and is frequently short lived. In one study, 36 per cent of 8- to 13-year-olds with newly diagnosed insulin-dependent diabetes mellitus developed an adjustment disorder (most commonly dominated by depressive symptoms) within the ﬁ  rst 3 months of diagnosis; 
50 per cent had recovered within 2 months.
(5) Similarly, in patients 
with chronic renal failure, psychological problems were reported in 60 per cent of children at the time of starting dialysis. One year later, after stabilization of their physical condition, the prevalence of disturbance was reduced to 21 per cent.
(6) It is very likely there-

fore that in many children with chronic physical illness, psychiatric disorders are most frequently transitory adjustment disorders to stressful times in the illness.
(c) Severity of illness/degree of life threat
More severe physical disorders and those constituting a greater degree of life threat are associated with a higher risk of psychiatric disturbance. In children with end-stage chronic renal failure, those with more severe disorders (on hospital haemodialysis) have been found to have more psychiatric disorder than those not yet requiring dialysis.
(7) More severely affected diabetic children and adolescents 
with a history of hospitalization for ketoacidosis in the previous year are more likely to exhibit psychiatric disorder than a control group of outpatients also with insulin-dependent diabetes mellitus.
(8) Post-
traumatic stress disorder (which by deﬁ  nition requires acknowledge-

(8) Post-
ment of perceived life threat), and high levels of post-traumatic stress symptoms have been found in children and parents up to a year after admission to Paediatric Intensive Care Units
(9); (a much higher pro-
portion than following admission to general paediatric wards), and up to 10 years after treatment for childhood cancer.
(10)Table 9.3.4.2  Factors related to the risk of psychiatric disorder and 
the form of its presentation
Nature of physical disorder (whether brain involvement)
Stage of illness (whether acute stresses involved)Severity of illnessDegree of life threatPsychosocial risk and protective factors in familyAge (developmental stage)Effects of illness and treatment procedures9.3.4 the relationship between physical and mental health in children and adolescents

SECTION 9  child and adolescent psychiatry 1742
The link between illness severity and risk of psychosocial impair-
ment may vary with the setting in which it is examined. Less severe physical impairment has been shown to be associated with a higher risk of behavioural problems in the school setting.
(7) T eachers may 
be less aware of the presence of an underlying physical disorder 
in this group who have less visible physical signs, and may make less allowance for these children than for those with a more overt disorder.
(d) Psychosocial risk and intrafamilial protective factors

When a physically ill child develops psychological symptoms, these are frequently attributed by families and professionals to the  presence of the illness and its stresses. It is important not to neglect consideration of other predisposing factors (i) within the child, for example genetic vulnerability, temperamental characteristics, (ii) in the family such as marital disharmony, lack of open communi-cation, maternal mental illness affecting parenting, and (iii) within the broader social environment such as bullying at school and poor peer relationships. These factors contribute to child psychopathol-ogy in ill as well as in healthy children. Conversely, protective fac-tors such as secure parent–child attachments, increased family social support in response to the physical diagnosis, as well as sen-sitive paediatric management of hospitalizations and stressful medical procedures may reduce the risk of developing psychiatric

disorder.
(e) Age (developmental stage)
Manifestations of psychological distress in ill children vary with 
each developmental stage. Preschool children have fewer cognitive resources to cope with discomfort and stressful medical procedures and are likely to rely on maternal support and distraction to cope with illness. Between 4 and 7 years of age, children may believe that 
illness has been caused by something bad they have done and that 
they should be punished.
(4) Clinginess to parents, fearfulness, sleep 
difﬁ culty, and oppositional–deﬁ  ant behaviour are seen in preschool 
children. The need for repeated painful procedures, for example with cancer chemotherapy, can lead to the development of speciﬁ  c 
needle phobia.
For school-age children, school life is a key aspect of their adjust-

ment to illness. Return to school after cancer chemotherapy can be associated with the development of school phobia, loneliness, and social isolation. School absence and having to catch up with school work, teasing, or even bullying, especially of children who look different, may also occur and contribute to lowered self-esteem and the risk of affective disturbance. Cognitive development in adoles-cence allows a greater understanding about the implications of chronic illness and the realities of death; depression occurs more 
frequently in this age group. Adolescents may begin to challenge 
and experiment with their treatment; they may fail to come to outpatient appointments or attend erratically. There may also be a decline in compliance with medical advice and adherence to treat-ment regimens.
(4) For example, diabetics may not follow dietary

(4) For example, diabetics may not follow dietary 
advice or pay reduced attention to their insulin regimen and moni-toring of blood sugars leading to poorer diabetic control. Adherence may be inﬂ  uenced by family factors; poorer metabolic control is 
associated with less family cohesion and a parenting style that is perceived as critical and negative.
(11) Adolescents aged 13–18 years 
with diabetes and co-morbid internalizing disorders, and dis-charged from hospital, have been found to be at greater risk of readmission up to 2 years later. This relationship was not found 
for younger children, suggesting that greater parental control of diabetes management (as is usual for younger children) may ameliorate the potential for psychiatric disorder to affect treatment adherence.
(12)
The way in which psychiatric disorder presents may inﬂ  uence its 
perceived signiﬁ  cance to health professionals and the likelihood of

(12)
perceived signiﬁ  cance to health professionals and the likelihood of 
psychiatric referral. Presentations with behavioural disturbances such as screaming, struggling, panicking, or a failure to comply with treatment are more likely to precipitate referral than inter-nalizing disorders such as depression.
Effects on parents and siblings
Whilst most families successfully adjust to the presence of a child with chronic illness in the family, this may act as a risk factor for psychological disorder. The incidence of marital break-up is not increased, but there are reports of increased marital distress. Interparental conﬂ  ict may not be directly expressed but instead 
diverted to excessive worry and focus on the illness, which can be very stressful for the child.
(13) In parallel with the heightened short-
term psychological difﬁ  culties found in ill children immediately

term psychological difﬁ  culties found in ill children immediately 
following diagnosis, a similar temporal pattern of disorder has been reported for parents and siblings. Most research has focused on mothers, who often undertake the practicalities of caring for a sick child. They may need to stop work themselves, leading to increased social isolation and a reduction in extra-familial support.
(14) Fathers and mothers often cope differently with the 
diagnosis; mothers tend to react by emotional release, whereas fathers are more likely to withdraw and concentrate on practicali-ties.
(14) Higher rates of maternal psychiatric treatment and nega-

tive affect have been found in families with a chronically ill child. The risk of maternal depression is greater for mothers of children with chronic as compared with newly diagnosed epilepsy; the burden of illness may impede parenting capacity and contribute to the development or maintenance of psychopathology in the children.
(13) Siblings may resent both the extra attention an ill 
brother or sister is receiving, and repeated separations from parents during periods of hospitalization. Their psychological adjustment is related to the degree of functional impairment
(15) and recent

(15) and recent 
physical health of their ill sibling, the extent to which family life is disrupted by the illness, and the psychosocial support available. The need for improved communication with healthy siblings has been identiﬁ  ed.
One disorder which highlights the complexities of interaction 
between living with a chronic illness and its effect on family members is AIDS. Vertical transmission from an infected mother to her unborn child has decreased in the last 10 years but there has been an increase in the number of adolescents with the virus due to survival of children with perinatally acquired HIV into adolescence in addition to adolescents acquiring the virus through other means. For many children with HIV , infection is also present in other family members, often the mother. Families have to cope with the 
disease itself and its treatment, the stresses of chronic illness which

disease itself and its treatment, the stresses of chronic illness which 
include an uncertain prognosis and the possibility of death as well as having to negotiate the stigma and social isolation that freq-uently accompany the diagnosis. Caregivers who are HIV positive themselves report poorer physical and emotional health compared with non-infected caregivers; this is associated with greater psycho-social impairment in the children—a higher risk of internalizing

1743
problems such as anxiety and depression, more externalizing 
problems e.g. oppositional behaviour and poorer academic function-ing. Disclosure of the diagnosis to affected children is often avoided; reasons include parental unease discussing their own HIV infection, fear of stigma, beliefs that the child is not emotionally ready to cope with the information and parents’ own distress.
(16) Children (aged 
6–16) who are not told their diagnosis have been reported as having more internalizing problems than those informed.
In the absence of rigorous treatment research in this area, the most important tenet of the psychological care of children with physical illness is based on good clinical practice, with clear and consistent communication between paediatricians, child psychiatrists and their multi-disciplinary teams. This allows early detection and intervention for psychological disorder.
Child psychiatrists frequently work closely with paediatric

Child psychiatrists frequently work closely with paediatric 
colleagues to assist in identifying young people at risk for psychiat-ric disorder, to provide assessment and treatment when indicated, and to give support and advice with regard to diagnosis and man-agement. Many paediatric units have regular weekly psychosocial ward rounds where professionals both from within the hospital and from the community—representing paediatrics, child and adolescent psychiatry teams, social work, and education—can meet to discuss the progress of the child from each perspective.
A full psychiatric assessment involving the child and the family 
will be carried out in referred cases. This needs to be preceded by a careful explanation to families about the reasons why a psychiatric consultation has been sought.
Important information about premorbid concerns and the 
child’s level of functioning may be obtained from schools, social workers, and other professionals involved with the family.

Speciﬁ  c psychiatric diagnoses should be treated appropriately. 
Children may develop acute confusional disorders associated with intracerebral infection or febrile illness. Manipulation of the ward environment to ensure: clear differentiation between night and day, that familiar toys are nearby, close family members are in atten-dance, and developmentally appropriate explanations are given to the child about where they are and what is happening, may help considerably. If behaviour is too difﬁ  cult for staff to safely manage 
and is interfering with treatment, sedative medication may be needed and should be discussed with paediatricians.
Children with adjustment disorders may be helped by psycho-

logical interventions. Management may include ways of decreasing existing stresses or helping individuals to adjust to them. Possible interventions include supportive counselling, individual therapy using cognitive behavioural principles, and family therapy.
When there is a chronically ill child in the family, parents often 
ﬁ nd it difﬁ  cult to maintain the usual boundaries. For example, dis-
ciplining an ill child may be associated with parental guilt; this can lead to increasing anxiety for children who exhibit increasingly oppositional behaviour in an effort to test the boundary limits. 
Discussion regarding parenting techniques in the context of these

Discussion regarding parenting techniques in the context of these 
feelings may be helpful. Parents also tend to increase their protec-tive responses to ill children and show more overinvolved parent-ing. If excessive it may impede the child’s development, but to a modest degree it may be helpful and advantageous.
Systematic desensitization together with relaxation and distrac-
tion techniques may be used to treat a speciﬁ  c needle phobia. This needs to be carried out in collaboration with ward staff taking

tion techniques may be used to treat a speciﬁ  c needle phobia. This needs to be carried out in collaboration with ward staff taking 
account of associated psychopathology, for example, oppositional behaviour, a generalized anxiety state, or an adjustment reaction. Treatment of the associated problems can often obviate the need for direct phobic treatment. When indicated, the latter’s success is likely to be dependent on external changes that reduce anticipatory anxiety. These might include minimizing the time the child needs to wait for treatment and ensuring that more experienced mem-bers of the medical team are responsible for cannula insertion.
Generalized symptoms of anxiety are not uncommon in parents

Generalized symptoms of anxiety are not uncommon in parents 
and children and may be manifested in different ways, for example, a young child may resume bed-wetting, a school-age child may become intensely distressed by being away from his parents, ado-lescents may experience difﬁ  culties sleeping, and anxious parents 
may become agitated with ward staff. Regular explanations from staff about the child’s condition and treatment may help to allevi-ate this anxiety. Communication difﬁ  culties within the family may 
contribute to anxiety and be helped by family meetings where dif-ﬁ culties can be shared. Relaxation and distraction techniques 
together with cognitive behavioural interventions may also be of beneﬁ  t. If symptoms are intense and interfering with physical treat-
ment, anxiolytic medication may be indicated.
Antidepressant medication may be considered for children and

Antidepressant medication may be considered for children and 
adolescents with a depressive episode. This should be discussed with the medical team to minimize drug interactions and side-effects that may exacerbate the physical condition of the patient.
Treating children with severe illness who may be receiving 
distressing and painful treatment can arouse intense emotions in the most experienced of paediatric staff. Regular meetings with 
mental health professionals may help them to process some of these feelings and prevent them impeding patient care.
Prognosis of psychiatric disorder in children with 
chronic physical illness
Many of the psychological difﬁ  culties experienced by chronically ill

Many of the psychological difﬁ  culties experienced by chronically ill 
children are short lived and do not continue into adult life. Overall, studies indicate that psychiatric outcome is not severely compro-mised in the majority of adult survivors. Persistence of disorder is related to the severity of childhood psychological symptoms (the more severe being more likely to last), persistence of physical symptoms into adulthood,
(17) and to the presence of physical dis-
order affecting the brain (Table 9.3.4.3).
The form of psychiatric symptomatology in childhood and 
adulthood may also be different; for example, cystic fibrosis sufferers, aged 8–15, have been found to report more eating related symptoms whereas symptoms of anxiety and depression are more prevalent in the adult group. With regard to cystic ﬁ  brosis, a consis-

tent association between disease severity in adulthood and psychi-atric disorder has not been shown. However, increased disease severity in childhood is associated with lower educational attainment; 
Table 9.3.4.3  Factors associated with persistence of psychosocial 
dysfunction into adulthood
Severity of childhood symptoms
Persistence of physical  symptoms into adulthood
Physical disorder involving the brain9.3.4 the relationship between physical and mental health in children and adolescents

SECTION 9  child and adolescent psychiatry 1744
in adulthood, employment is associated with both higher academic 
achievement and less depressive symptoms.(18)
Many studies suggest that by adulthood, most survivors of 
childhood cancer are indistinguishable from the general popula-tion with regard to psychosocial outcome. However, more detailed analysis suggests that factors such as age at diagnosis, site of the tumour, and nature of treatment (e.g. cranial irradiation) may inﬂ uence cognitive and psychological outcome. For children and 
adolescents up to age 18 diagnosed with brain tumours, cognitive deﬁ cits and psychosocial problems increased with age and time 
since diagnosis.
(19) As survival has increased, adults are exposed to

(19) As survival has increased, adults are exposed to 
the chronic toxic effects of treatment such as endocrine abnormali-ties, cardiac or pulmonary problems, and infertility. Follow-up of childhood cancer survivors, to a mean age of 28, revealed that cur-rent physical functioning, including pain, was associated with sui-cidality even after accounting for treatment and depression vari-ables. Y ounger age at diagnosis, longer time since diagnosis, and cranial irradiation were also important risk factors.
(20) Survivors of 
acute lymphoblastic leukaemia and Wilms’ tumour did not show increased psychopathology as adults but had more difﬁ  culties with 
interpersonal functioning and day-to-day coping.
(21)
Individuals with intracerebral pathology maintain high levels

(21)
Individuals with intracerebral pathology maintain high levels 
of disorder in adulthood, especially with regard to behaviour and social isolation. By contrast, patients with congenital heart disease surgically corrected in childhood, are not at increased risk of psychiatric disorder as adults.
Although young adults with end-stage chronic renal failure 
report more episodes of psychiatric disturbance than healthy matched controls before 17 years, they do not necessarily have increased psychopathology in late adolescence and adulthood. In common with survivors of other chronic childhood disorders,
(17)
the majority of adult renal patients are reported as functioning well socially, but they are more likely than age-matched controls to be living with their parents, to have less school qualiﬁ  cations, higher 
rates of unemployment, and fewer intimate relationships outside the family.
Care of the dying child

Children at different developmental stages differ in their under-standing of death. They gradually acquire components of the death concept; between 9 and 11 years of age, most children have reached a full understanding, acknowledging that it is permanent, inevita-ble, and universal. However, experience of serious illness and death interacts with the stage of understanding, so that children aged 5 or younger may have a more mature understanding and exhibit symp-toms of anxiety about death. There is evidence that even young children with terminal illness are aware that they are dying, although they may not tell anyone that they know.
(22)
Parents (and professionals) often ﬁ  nd it difﬁ  cult to talk about 
death with children. This is likely to interfere with coping for the whole family. Families with an open pattern of communication do better psychologically.

(22) Mental health professionals may have a 
role in facilitating this discourse, promoting parents’ conﬁ  dence, 
and competence in communicating with their children. This will help the whole family to begin the process of mourning.
Children need information, reassurance, an opportunity to 
express their feelings, and adults with whom they can do so. As children lack the vocabulary of adults they may often exhibit their distress by behavioural changes, for example, bed-wetting, 
difﬁ culty sleeping, and school refusal. Children and their siblings 
faced with death need clear, simple, and truthful explanations. They should not be pushed to talk, nor frightened with excessive medical detail.
Dying and grieving lead to a whole range of distressing feelings.

Dying and grieving lead to a whole range of distressing feelings. 
This is part of a normal process, and mental health professionals can help their colleagues and families to acknowledge that this upset is acceptable.
Bereaved children frequently model their grief experience on 
what they perceive as being acceptable in the family, and an overt denial of upset by parents may lead to psychological difﬁ  culties in 
the child. The issue of whether to involve siblings after the death of the child in funerals or graveside visits often arises. If children are prepared for what to expect, involvement can be helpful in 
enabling them to acknowledge that a change has taken place and 
other people are feeling as sad as they are.
(22)
Mothers are involved in nursing and caring for their dying

(22)
Mothers are involved in nursing and caring for their dying 
children. They report an excess of depression, problems of helplessness, and a fear of being unable to cope with the child dying. Parents may feel that they can never fully recover from the loss of a child. Fathers tend to report more difﬁ  culties with feeling 
left out of the ill child’s life and then with worry about their spouse being too preoccupied with the dead child. The effects of a child’s death on family life can be traced even years after the death.
(22)
Formal follow-up after bereavement may help to identify those families and individuals experiencing psychological reactions that may beneﬁ  t from more intensive support.
The effects of psychiatric disorder on the 
course and outcome of physical illness
Psychological disorder, as well as being a consequence of both acute

Psychological disorder, as well as being a consequence of both acute 
and chronic physical ill-health, may also have an impact on the course of physical illness.
An increasingly recognized disorder in this respect is post-traumatic 
stress disorder. Sudden physical trauma, such as burns and road trafﬁ  c accidents, are examples of antecedents. Victims of road 
trafﬁ c accidents between 5 and 18 years of age, particularly those 
who experience high levels of distress immediately after the accident, are at greatest risk of exhibiting post-traumatic stress symptoms 3 months later.
(23) Such responses may be contributed 
to not only by the accident itself but also by the medical procedures that take place on arrival in hospital. Surgical collars, intravenous infusions, and monitoring equipment can be associated with intense fear.
(23) Children with acute severe sepsis such as meningo-

coccal disease admitted to paediatric intensive care units are also at risk of developing similar symptoms.
(24) In turn, these reactions 
can have an effect on the child’s ability to co-operate with future hospital attendance, medical, and surgical interventions. Stress reactions may be ameliorated, to some extent, by the provision of age-appropriate information about what has happened and what is going to happen.
The diagnosis and treatment of such disorders may be impeded 
by the fact that follow-up for young people may not be at the admitting hospital. Burns units and paediatric intensive care facili-ties are often at tertiary centres some distance from the patient’s home. General practitioners and local paediatricians have a role to play in assessing how the family is coping, speciﬁ  cally regarding

1745
symptoms of post-traumatic stress. Child psychiatry involvement 
may be appropriate if psychological treatment is required both during admission and at follow-up. Cognitive behavioural inter-ventions with individual children and families may be used to alleviate symptoms.
Affective symptoms, particularly depression and anxiety, are 
not uncommon following an acute medical admission and may interfere with physical treatment. For example, an adolescent admitted to paediatric intensive care with meningococcal disease requiring a partial limb amputation could develop a depressive dis-order. Symptoms of despair and hopelessness coupled with a lack of interest and energy may impede the physiotherapy programme, delay mobilization, and hospital discharge. Paediatric staff need to be alert to such potential sequelae and to have child psychiatric colleagues readily available for assessment and treatment.
Exacerbation of chronic illnesses such as asthma can be

Exacerbation of chronic illnesses such as asthma can be 
precipitated by emotional disturbance; adolescents aged 11–17 with anxiety or depressive disorders reported more asthma symptoms in the previous 2 weeks than young people without these affective diagnoses.
(25) Adjunctive psychological treatments such as family 
therapy have been shown to lead to an objective improvement in airways disease,
(26) compliance, and reduced hospital admissions.(27)
Somatization and somatoform disorders
Disorders presenting with functional physical 
symptoms and somatization
‘Functional’ somatic symptoms with no obvious organic explana-

tion are frequent in childhood. Children have a limited vocabulary for expressing their emotions and often communicate their distress by means of physical symptoms. Somatization refers to this pro-cess. In some cases these symptoms become persistent with associ-ated functional impairment; this may lead to consultation. The deﬁ nitions of somatization disorder (one of the somatoform disor-
ders) used in ICD-10 and DSM-IV are too stringent for children (in that diagnosis requires multiple physical symptoms over years). Other disorders (namely somatoform pain disorder, dissociative/conversion disorder, and neurasthenia) are seen in children and adolescents. The risk factors for somatization in this population are shown in Table 9.3.4.4.Aches and pains and somatoform pain disorder

Aches and pains (often abdominal pains and headaches) are a com-mon manifestation in young children. Between 2 and 10 per cent of children in the general population have problems in this area. Mothers assess the child’s symptomatology with speciﬁ  c regard 
to whether the child is ‘pretending’ , ‘upset’ , or ‘ill’ and generally respond appropriately. They recognize that children may experi-ence symptoms as a result of stress or use them to avoid something they ﬁ  nd difﬁ  cult.
Abdominal pain commonly leads to a general practitioner con-
sultation and may account for 10 per cent of new appointments with paediatricians. In only a few of these cases is serious organic pathology found. Lack of identiﬁ  able organic pathology does not 
imply a psychogenic aetiology. The latter is rather supported by evidence that psychological events inﬂ  uence the symptoms.
Children who somatize tend to have a family history of physical

Children who somatize tend to have a family history of physical 
ill-health and parental illness. In some cases there are also psycho-social difﬁ  culties in the family. There is an association with stressful 
life events. Co-morbid internalizing disorders (depression and anxiety) are commonly present.
(28)
In adolescence, headaches become a prominent symptom, 
peaking in prevalence at 12 years of age. As with abdominal pain in younger children, they are frequently preceded by physical or psychological precipitants, such as academic or social stresses in school or difﬁ  culties at home. Headaches lead to absence from 
school but are not associated with underachievement. A family history of migraine is common.
As deﬁ  ned in ICD-10, in persistent somatoform pain disorder,

As deﬁ  ned in ICD-10, in persistent somatoform pain disorder, 
severe distressing pain occurs in association with emotional conﬂ  ict or psychosocial problems that are sufﬁ  cient to allow the 
conclusion to be drawn that they are the main causative inﬂ  uences. 
The result is usually a marked increase in support and attention, either personal or medical.
In trying to best manage severely affected children, close collabo-
ration between paediatricians and child psychiatrists is helpful. The

ration between paediatricians and child psychiatrists is helpful. The 
lack of demonstrable organic pathology should be communicated and professionals should help the family to make the link between physical symptoms and psychological precipitants with the help of a written diary if necessary. It is important to reduce the attention given to the physical symptoms in order to decrease the resulting functional handicap. Early return to school together with the resumption of normal activities should be encouraged. The short-term prognosis for presentations to medical services is good, with 75 per cent of children recovering within several months.
Dissociative/conversion disorder

Children and adolescents present as if having a physical disorder affecting voluntary motor or sensory functioning, although none can be found; the symptoms correspond to the patient’s idea of physical disorder, which may not coincide with physiological or anatomical principles. Aetiologically, the disorder is believed to arise largely unconsciously and to represent an escape from an unbear-able personal conﬂ  ict. It usually manifests in adolescence and is 
more common in girls. The most common presentation is neuro-logical with disturbance of motor function such as weakness of legs, paralysis of a limb, or bizarre gait. Multiple symptoms often occur.
Premorbid psychopathology in the child and family are often 
absent, although perfectionistic and conscientious traits with con-cerns about academic performance and a child and family focus on 9.3.4 the relationship between physical and mental health in children and adolescents

Table 9.3.4.4  Risk factors for somatization in children and 
adolescents
Individual: Personal experience of physical illness
Enhanced focus on physical sensationsSomatic attributionsConscientious, vulnerable, sensitive, anxious personalities 
with particular concerns about peer relationships
High achievement orientation
Family: Physical health problems
Psychiatric problemsParental somatizationEmotional overinvolvementLimitations in the ability to communicate about 
emotional issues
Environment: Life stresses e.g. school, teasing or bullying, academic 
pressure

SECTION 9  child and adolescent psychiatry 1746
high achievement have been noted. Overconcern with physical 
health and illness often characterize these families; frequently there is a family history of physical health problems. Families often pres-ent as being close, but communication, particularly regarding emo-tions, may be limited.
It is assumed children develop conversion disorders as an uncon-
scious means of escaping a situation with which they cannot cope. This includes intolerably high academic expectations (often the child’s own), unresolved family conﬂ  ict, and, in a minority of cases, 
sexual abuse. The disorder is often precipitated by minor physical illness and may also occur in children with identiﬁ  ed organic 
pathology, for instance the development of pseudoseizures in an individual with epilepsy.
The majority of these patients are managed by paediatricians.

The majority of these patients are managed by paediatricians. 
After investigations have excluded organic pathology and a psycho-genic contribution is suspected, this needs to be communicated to the family. The shift from physical to psychological factors may be difﬁ  cult for the family to accept; information may need to be 
conveyed slowly ‘at a pace the family can cope with’ . A collaborative approach between paediatricians and child psychiatrists is important. A persistent focus on physical aetiology may be unhelp-ful but in management it is more useful to focus on the handicap caused by speciﬁ  c symptoms rather than on their cause by intro-

ducing a programme of rehabilitation and physiotherapy directed at these features, including school attendance. Psychotherapeutic work, both individually and with the family, may help the family understand the factors maintaining the child’s symptoms and 
explore any identiﬁ  ed stressors or conﬂ  icts. Time can also be spent 
helping families to consider alternative strategies they may use to cope with future conﬂ  icts.
Chronic fatigue syndrome (neurasthenia in ICD-10)
This is operationally deﬁ  ned as disabling physical fatigue of over 
6 months’ duration, unexplained by primary physical or psychiat-ric causes. There are often other unexplained somatic symptoms and a strong belief by the patient and their family that the aetiology is physical.
(29) It might be considered as one of the somatoform 
disorders, as similarities are shared with regard to aetiology and management.
There is no ﬁ  rm evidence that chronic fatigue syndrome results

There is no ﬁ  rm evidence that chronic fatigue syndrome results 
from a speciﬁ  c viral infection but a physical illness is often the 
precipitating factor. There is frequently a family history of physical illness and a preoccupation with physical symptoms. Parents invariably attribute the symptoms to an organic aetiology. Children tend to be described as high achieving and perfectionistic, as well as sensitive, vulnerable and anxiety-prone; onset can be temporally related to transitions at school, for example transfer to secondary school. Depressive mood changes are common and on assessment depressive disorder is found in one-third of cases.
(29)
Chronic fatigue syndrome can be extremely disabling. A self-

(29)
perpetuating cycle is set up whereby fatigue and the resultant inactivity lead to loss of muscle bulk and deterioration in physical ﬁ tness. Activity becomes increasingly difﬁ  cult and is avoided, lead-
ing to a further deterioration in physical ability. An essential focus of treatment is to disrupt this cycle.
Management is often multi-disciplinary including paediatri-
cians, physiotherapists, school teachers, and child psychiatrists. A clear explanation of the results of physical investigations and the fact that no serious organic pathology has been found is important. Focusing on improving symptoms, as opposed to debating aetiol-
ogy, is most helpful. Helping the family to shift from a purely physical model to one that includes psychological factors in main-taining symptoms may be difﬁ  cult and needs to be negotiated slow-

ly. In particular, enabling them to see the disorder as an interaction between physical, social, and emotional factors can be useful.
Treatment ingredients usually include a graded exercise pro-
gramme, a progressive return to school, and work with the family to facilitate engagement and address factors that may be impeding recovery. Antidepressants may be useful for co-morbid depressive disorder. There is an evidence base for both cognitive behaviour therapy (CBT) and graded exercise in adults and one study which demonstrates the effectiveness of CBT in adolescents.
(30)
Treatment of functional symptoms and somatoform 
disorders in children and adolescents: research evidence
There are few satisfactory controlled studies on the effects of

(30)
There are few satisfactory controlled studies on the effects of 
treatment for childhood somatization. Most work on children with somatoform disorders has been based on small groups with severe problems, and the management advice outlined above is derived from the conclusions of experienced clinicians and open-treatment case reports. However, there is some evidence from controlled studies indicating the efﬁ  cacy of a cognitive behavioural family 
intervention for recurrent abdominal pains in children.
(31) For 
hospitalized children with severe, recurrent abdominal pain, paren-tal attribution of symptoms to psychological factors facilitated resolution.
(32) The superiority of relaxation training over placebo 
in reducing migraine attacks has been shown.
Outcome of functional somatic symptoms and 
somatoform disorders

Of adults with a childhood history of abdominal pains, 50 per cent 
have recurrent symptoms in adult life despite a pain-free period in adolescence; they also have an increased prevalence of psychiatric disorders (particularly anxiety disorders).
(33) Childhood conver-
sion disorder is generally associated with a good outcome; recov-ery is usually complete by 3 months. When children (9–16 years) were followed up 4 years after a conversion disorder from which 85 per cent had recovered, 35 per cent had a mood or anxiety dis-order; affective disorder was higher (100 per cent) in the minority who had failed to recover as compared with 23 per cent in those who were better.
(34) In young people with chronic fatigue syn-

drome, recovery or marked improvement in symptoms can be expected in 50–75 per cent of cases in the short to medium term. School non-attendance may be over a year and time to full recovery 3 years or more. There are indications of an increased likelihood for the development of psychiatric disorder after recovery.
(35)
Somatic and psychological symptoms are intimately linked. Changes in physical health can affect psychiatric outcome. Conversely, emotional distress may affect adherence to treatment, and it is sometimes expressed through physical symptoms. Awareness of this interplay is important and should be mirrored by a close working relationship and close communication between paediatricians and child psychiatrists.

1747
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9.3.5 The effects on child 
and adult mental health of adoption and foster care
Introduction: mapping the terrain
Adoption and foster care are important ‘solutions’ to identiﬁ  ed 
problems or risks, but potentially they are also contributors to problem behaviours or emotional difﬁ  culties. In their problem-
solving role, they are seen as potential solutions, not only to actual 9.3.5 the effects on child and adult mental health of adoption and foster care

SECTION 9  child and adolescent psychiatry 1748
or future mental health problems of children, but also to the adverse 
effects of involuntary childlessness.
This chapter concentrates on the impact of adoption and foster

care on the children placed, but their role in problem solution or problem generation for adults is also touched on. Adoption is more often than not a satisfactory way of meeting the need to become parents for those childless couples who succeed in having a child placed with them (a tiny minority of the involuntary childless). It is very rarely a solution to the problems of a parent who gives up a child for adoption whether voluntarily or involuntarily. Studies of adults who relinquished children indicate that the reaction to the loss of their child may be associated with moderate distress or may lead to a long-term grief reaction, which in turn will potentially harm children subsequently born to that parent. One must also note that some parents who lose a child to adoption or foster care are themselves children, sometimes not yet in their teens, whose needs are often overlooked in the interests of providing for the infant.

Fostering and adoption started as very similar processes, diverged 
in Europe and North America in the ﬁ  rst half of this century, and 
are now much closer together again. The ‘total severance’ model of legal adoption—the type that most people in Europe, the United States, and Australasia immediately recognize—has a short history. In the United Kingdom it was not until the passing of the 1958 Adoption Act that secrecy became the norm. The ‘sealing’ of birth information started in the United States around 1948 but it was not until 1991 that Alabama ‘sealed’ its adoption records.
(1) This 
experiment of totally closed adoption was short-lived, and many countries have introduced legislation to allow adult adoptees and/or birth relatives to access identifying information that allows them to seek each other out.
(2) ‘Open’ adoptions, in which some degree 
of contact between the adopters, the birth parents, and the children is maintained after placement, are increasingly common.

As countries have become richer, the need to place children for 
adoption has diminished and the number of infants placed at the request of their parents has fallen well short of the ‘demand’ of those wishing to start a family through adoption. In consequence, it has been possible to encourage potential adopters to ‘stretch’ their notions of parenthood, and to place older children, those with disabilities, and those with behavioural or emotional problems with adoptive parents as well as with foster parents. The main remaining difference between adoption and foster care is that the majority of children placed in foster homes live there for compara-tively short periods before returning to their families of origin. They are best seen as supplementary rather than substitute parents,

although in all ‘ﬁ  rst world’ countries long-term or ‘permanent’ fos-
ter care is an important option for a minority of those entering public care, especially in those countries (the majority) who rarely use adoption as a route out of care.
Adoption and foster care will impact on the mental health of the 
children in different ways, which may be considered along six main dimensions (see Box 9.3.5.1). The dimensions interact differently for different children. An infant placed from an Asian country might be adopted by childless relatives in Europe and have had a positive early experience of parenting, or might have experienced very adverse early nurturing and be adopted by strangers of a different ethnic origin. The child placed at six may have had good care from one or both parents until some traumatic event led to the need for an adoptive placement, or the child may have been seriously maltreated and had several placements before ﬁ  nally

joining a substitute family.The nature of the evidence on the impact of 
adoption and fostering on mental health
The actual or potential problems most obviously associated with 
child placement are those resulting from separation and loss. Brodzinsky et al .
(3) have made signiﬁ  cant contributions to our 
understanding of the psychology of adoption. Put simply:
. . . for later-placed children, the loss of family or surrogate family connections is overt, often acute, and sometimes traumatic. In con-trast, for children placed as infants, loss is, of necessity, more covert, emerging slowly as the youngster begins to understand the magnitude of what has happened. . . . In addition, there may be loss of a clear sense of genealogical connections and, in the case of transracial and inter-country adoption, loss of cultural, ethnic, and racial ties.
The impact of loss will also vary with the child’s temperament, 
and the work of Rutter,(4) and of others who have written on ‘resil-

ience’ , are important sources. A ‘born worrier’ will go through life wondering what there was about him or her that was not worth keeping, and no amount of positive parenting will make this angst go away; a resilient child will shrug away the past and make the best of even not particularly good parenting by the substitute parents.
It is important, before considering the research ﬁ  ndings, to take 
note of the limitations of our knowledge on the long-term outcomes of foster care and adoption. Turning ﬁ  rst to the characteristics of the 
children, studies of family placement often include both infants and older children, those with emotional difﬁ  culties and those without.

children, studies of family placement often include both infants and older children, those with emotional difﬁ  culties and those without. 
Some studies of foster care include children placed temporarily alongside others placed permanently, and in some US studies the term ‘foster care’ includes all children in out-of-home placements 
(for family placements the term ‘foster family care’ is used).
At the other end of the process a broad range of ‘outcome’ 
measures is used
(5) and ‘success’ rates vary depending on the meas-

ures used and the length of time between placement and reported outcome. The well-being of the young adult (using a range of standardized instruments) is the most reliable outcome measure but more often ‘output’ measures are used. (Was the child placed? Was legal adoption completed? Was a satisfactory reunion with the birth parents achieved during childhood or as an adult?). Measures of satisfaction of the different members of the adoptive family are also used. Unsurprisingly, therefore, reported ‘success’ rates have varied between below 50 per cent and around 95 per cent.
Box 9.3.5.1 Dimensions of family placement
◆ The age of the child at placement.
◆ The degree of disturbance of the child prior to placement.
◆ The nature of attachments with birth family members and 
short-term foster carers.

◆ (For those in foster care) the duration of placements, the fre-quency with which they occur, and whether the child returns to the same foster carers on each occasion.
◆ (In the case of adoption) whether the child is adopted within the family (step-parent or relative adoptions), by foster carers to whom the child is already attached, or by parents not known previously (stranger adoption).
◆ Whether or not the child is adopted or fostered by parents of the same cultural and ethnic background or country of origin.

extremely complex. When, as with adoption or permanent foster-ing, the aim is for the child’s life chances to be improved by their becoming fully a part of the new family, it becomes impossible to unpick the very many variables that will have had an impact on the mental health of the young person between placement at 6 weeks and maturity at around 26. (There is some evidence that adopted people move towards emotional maturity at a slower pace—not surprisingly with at least two extra hurdles to surmount: that of separation and loss, and that of making sense of their adoptive identity). In longitudinal studies, if numbers are large enough, it is possible to control for the major variables such as age at placement, disability, and emotional or behavioural problems at the time of placement. However, the many aspects of parenting, and the nature of any therapeutic input may all have had an impact on the place-ment. The researchers may seek the opinions of parents and children as to what

However, the many aspects of parenting, and the nature of any therapeutic input may all have had an impact on the place-ment. The researchers may seek the opinions of parents and children as to what they found helpful, but clear causal relationships between outcomes and variables such as parenting styles, models of social work practice, and therapy cannot be claimed.

In summary, whilst researchers have, for many years, sought 
to bring academic rigour to their studies, family placement remains an ‘untidy’ subject. The more complex the placement circumstances and the longer the timescale, the more difﬁ  cult it is to attribute success
to any one factor, type of placement, or model of intervention.
A review of the research evidence on outcomes
The above section explains why, although there are some random controlled trials of treatment approaches and of short-term foster care models, the literature contains more research syntheses of the different aspects of family placement
(5–10)  than ‘classical’ systematic 
reviews. The ﬁ  ndings from the large volume of quantitative and

reviews. The ﬁ  ndings from the large volume of quantitative and 
qualitative research will be summarized under the broad headings of time-limited foster care placements and placements made with the intention that the child will become a full part of the adoptive or foster family. The emphasis will be on the second group, which will be further subdivided into placements of infants and place-ments of older children.
Time-limited placements
In general terms, short-term foster care is used along with other services in an attempt to improve family functioning so that the child may beneﬁ  t from increased stability in the family home or as 
a short-term crisis intervention measure. The aims of short-term fostering can be summarized as: temporary care; emergency care; assessment; treatment and ‘bridging’—to independence or between placements following placement break down.
(7)
Generally short-term placements used as part of family support

(7)
Generally short-term placements used as part of family support 
are successful in that few placements actually break down and most parents express satisfaction with the service. This is especially so if the placement follows careful preparation for the child, the birth parents, and the foster parents and if those who need a series of placements return to the same foster family. Several UK researchers have found that a ‘keep them out of care at all costs’ attitude tends to prevail in child welfare agencies, thus leading to too many ill-planned and ill-matched emergency placements, which in turn lead to placement break down and to unnecessary moves in care.
T esta and Rolock
(11) conclude broadly positively from an over-
view of treatment foster care research in the United States, and Fisher and Chamberlain(12) report better outcomes for very trou-

bled children in multi-systemic treatment foster care than for a ‘service as usual’ group. (These approaches involve placement with specially recruited, trained, and ﬁ  nancially rewarded foster carers

on a time-limited basis. Intensive multi-agency support is provided to the parents, foster carers, and children.) Though placement sta-bility remains a problem, behavioural improvements are reported and these schemes are well rated by most of the young people and their foster carers. Some researchers report a problem of ‘over-staying’ , but this should perhaps be reframed as a success, in that some young people settle in so well that, against the odds, the task-centred foster family becomes a ‘secure base’ and the foster parents continue to provide support to the young people as they move into adult life.
Associations have been found in some studies between positive 
child outcomes and practitioners who facilitate good contact between the birth parents, foster carers, and the child; provide support to the foster carers and the birth parents; and take a multi-agency approach to treatment of the child and parents before, during, and after placement.

Adoption and long-term foster-family placement
Whilst, in the United Kingdom and North America, adoption is considered to be the major placement option for most young children who cannot remain with their birth parents, opinion is divided (often along country lines) as to the importance of long-term foster family care as a placement of choice. Practice also varies in different countries in respect of placement with relatives. In most countries it is the exception rather than the rule for rela-tives to adopt (foster care, guardianship, or informal arrangements being preferred) whereas in the United States legal adoption by relatives tends to be encouraged.
(13)
(a) Outcomes for children placed as infants

(13)
The largest volume of research on the long-term outcome of adop-tion concerns children placed ‘voluntarily’ as infants. However, inevitably, the practice referred to in these studies is already dated by the time the long-term outcomes can be measured some 20 years or so after the child was placed. Although some may have been born to mothers who had poor antenatal care, few of these early-placed children will have experienced neglect or maltreat-ment. However, with the growth of inter-country adoptions, studies of infants placed more recently are more likely to include substantial numbers of children who have experienced adverse conditions during their early months. It is likely that disruption rates will be higher than they have been in the past.
(b) The impact of placement in the short-term
An important source of detailed information on short-term outcomes of infant placements is the longitudinal study by Rutter et al .

(14) which compares young Romanian children placed with 
British families with a cohort of English infants placed in ‘stranger’ adoptive families. Reactions to placement of the English infants who had generally good postnatal care are predictable in the light of knowledge about child development, attachment, separation, and loss. Those placed quickly settle with no obvious signs of stress; those with adverse early experiences including institutional-ization (most of the Romanian infants) also appear to settle well if placed in their early months. Those placed when older than 6 months are more likely to show stress reactions at the loss of a carer to whom they are beginning to be attached, or to show 9.3.5 the effects on child and adult mental health of adoption and foster care

SECTION 9  child and adolescent psychiatry 1750
adverse reactions resulting from early maltreatment, neglect, or 
institutionalization.
(c) Signs of stress during childhood
The more robust studies of the mental health of adopted infants in their middle years and early adolescence are those that prospective-ly follow them as they grow-up. The conclusion drawn from these studies is that children placed with substitute families as infants tend to do better at each stage than non-adopted peers living in the generally adverse environments in which the children were likely to have lived had they remained with their birth parents.
All studies have found that, even for those with poor antenatal

All studies have found that, even for those with poor antenatal 
and birth history or who experience adverse circumstances in their early months, subsequent physical and cognitive development is generally good. However, children adopted as infants appear to be at a slightly higher risk of experiencing problems in their social, emotional, and behavioural development compared with other children raised in similar socio-economic circumstances. This is 
particularly the case with adopted boys. Information from longitu-

dinal studies is supplemented by studies of clinical populations, such as those whose parents seek psychiatric help for them. Rates of maladjustment appear to be higher around the age of 11, and decrease as the children move into later adolescence. Some studies report that adopted children are more vulnerable on some meas-ures of behavioural and emotional development than others, including an inability to settle, restlessness, a tendency to lie or fan-tasize, and difﬁ  culties in getting on with their peers and teachers. 
Low self-esteem and feelings of insecurity are also more likely to be present amongst children in their middle years and adolescence.
(d) Long-term outcomes
There is a lack of recently published quantitative studies of the well-being of adults adopted as infants. Summaries of the research
(3,6,7) report that few of those placed as infants (around 5

(3,6,7) report that few of those placed as infants (around 5 
per cent) will leave their adoptive families before the age of 18, in circumstances of conﬂ  ict, which can be described as ‘adoption 
break downs’ . Qualitative studies have reported that around 80 per cent of both adopters and adoptees express broad satisfaction with the growing-up experience. Howe
(15) uses in-depth interviews with 
the parents of adult adoptees to analyse the mental health problems that have persisted into adulthood and reports that, when more serious problems do emerge, the issue of adoptive identity often underlies a range of presenting symptoms. Also, amongst the over 80 per cent of adults who are generally satisﬁ  ed with the experience 
of growing-up adopted are some who continuously or episodically have a sense of unease around questions of identity and the reasons

of growing-up adopted are some who continuously or episodically have a sense of unease around questions of identity and the reasons 
why their birth parents ‘gave them up’ for adoption.
(2) The most 
authoritative recent research on long-term outcomes is the Swedish cohort study of Lindblad et al.
(16) These authors compared popula-
tion data on nearly 6000 inter-country adopted adults (mostly placed when under the age of 5) with their non-adopted peers. They note that whilst there were more similarities than differences, the adopted children were more likely than peers brought up in similar circumstances to have psychiatric problems, includingsubstance abuse, and there was a higher suicide rate.
In summary, when well-being and mental ill-health are the out-

come measure used, adults who were adopted as infants tend to be healthier, have higher IQ scores, lower rates of criminal behaviour, and fewer psychiatric symptoms than non-adopted peers from similar backgrounds to those into which they were born and tobe broadly similar to those brought up by birth parents living in similar circumstances to the adopters. However, the larger scale 
studies that allow for the control of the many intervening variables tend to lack detail on the children’s experiences of family life and of any therapeutic interventions. It is therefore unclear whether any differences can be associated with adoption per se  or with the more 
advantaged home circumstances of the adopted children.
(e) Children placed when past infancy

Researchers and clinicians tend to agree that beyond 6 months of age, the risks of moving children increase, and the older the child at placement, the more likely it is that there will be difﬁ  culties in the 
child’s behaviour, which increase the risk of placement break down. Some delays in placement are caused by incompetence or poor practice. However, the main reason for delay in placement (some-times referred to as ‘drift’) is contested legal proceedings. In most countries it is only possible in extreme circumstances to place a child for adoption without the consent of the birth parents, although adoption by long-term foster carers they have lived with for some years sometimes occurs. In the United Kingdom, United States, and Canada it is not uncommon for parental consent to be dispensed with by court order, but human rights legislation and the

attempts at reuniﬁ  cation mean that few children are placed from 
care before the age of 6 months. International adoptions tend to be delayed because of the search within the country of origin for an in country placement, or because of legal formalities.
(f) Medium-term outcomes
Many of the children placed when older bring problems with them into placement, to which may be added those discussed earlier, which are speciﬁ  cally associated with being adopted or fostered. 
For those placed from overseas, the difﬁ  culties are those commonly 
associated with institutionalization and privation of affection and consistent care. For a large proportion of those placed from care, the problems are those associated with maltreatment or neglect, including attachments with parent ﬁ  gures that may have been 
anxious, ambivalent, or avoidant, followed by the loss of those attachment figures. They may also have been separated from siblings and experienced multiple changes of carer.

Rushton and Dance
(17) provide detailed acc ounts of the beha viour 
of 133 English children placed when over the age of 5. Eight years after placement, 19 per cent of the children had left their place-ments and only just over half of the 99 continuing placements were in the ‘continuing/happy’ group. Behaviours their parents had difﬁ  culty managing included over-activity, aggression, and 
destructiveness.
(g) Longer-term outcomes for late-placed children
Whilst some children placed in positive environments that provide committed and loving parenting and stability will recover from the adverse effects of early signiﬁ  cant harm, developmental recovery

cannot be anticipated in all cases. From a longitudinal study of over 1100 ‘hard-to-place’ children placed in adoptive or permanent foster families not previously known to them, Thoburn
(18) found 
that one in ﬁ  ve of the placements had disrupted between 2 and 
6 years after placement. There was a strong and statistically signiﬁ  -
cant association between disruption and the age at placement (see 
Fig. 9.3.5.1). Of those aged between 7 and 8 years at placement, one 
in ﬁ ve experienced placement break down; this proportion rose to 
almost one in two for those placed between the ages of 11 and 12. The graph is less stable for teenagers, in part because numbers are smaller and statistics less reliable, and in part because families are

1751
more likely to ‘hang on in’ if they know the young person can be 
helped to leave home ‘respectably’ in a year or so. More recently, 
Rushton and Dance(17) found that the placements that disrupted 
did so between 6 months and 7 years after placement (a mean of 34 
months). Rushton and Dance(17) followed up 90 children placed 
for adoption when aged at least three for an average of 7 years. 
Seventeen per cent of placements had disrupted (mostly before 
adoption was ﬁ  nalized), and for a third of those still in placement, 
there were many problems, which were often getting worse. 
Festinger followed up for 4 years 516 American children placed 
from care at a mean age of 2 years. The lower disruption rate (10 
per cent) when compared to the UK studies may be explained by 
the younger age at placement and also by the fact that roughly half 
were adopted by relatives. She reported that many of the parents in 
the continuing placements reported difﬁ  culties and unmet needs.

Variables about the child and 
pre-placement history
Researchers and clinicians concur that, in addition to age at place-
ment, variables relating to the child’s behaviour and emotional 
well-being at the time of placement are most strongly associated 
with better or worse outcomes. These in turn are linked with 
biography, including experiences of early parenting and multiple 
caregivers. Having experienced early abuse or neglect has been 
found to be independently associated with less positive outcomes, 
whilst more positive outcomes are reported even for late-placed 
children who had formed a good-enough attachment with a parent 
or other main carer during the ﬁ  rst few years of life.
Thoburn et al.(20) found that children of minority ethnic origin, 
whether placed with a family of the same or a different ethnic

whether placed with a family of the same or a different ethnic 
origin, were no more likely to experience break down than white 
children placed with white families. However, qualitative studies 
note that parents of a different ethnic and cultural background to 
the child have extra hurdles to overcome in the parenting process, 
and that some are unable to bring the child up to feel pride in his or 
her heritage, culture, and appearance, with consequent problems 
for self-esteem and identity.
Variables about the adoptive or foster families
Early studies reported an association between less positive 
outcomes and there being a ‘home-grown’ child younger or close in age to the placed child, but these have not been replicated more 
recently. The age of the adopters, whether they are single or in a

recently. The age of the adopters, whether they are single or in a 
partnership, experienced parents or childless, have not been consis-
tently found to be signiﬁ  cantly associated with placement break 
down. Two in-depth prospective studies of long-term foster care(21)
and adoption(22) conclude that those new parents do best who can 
empathize with both the child and the family of origin, who enjoy 
a challenge, who have the skills to help the child with disabilities or 
emotional problems, and who, for older-placed children, can give 
out love even if the child gives little back and can ﬁ  nd pleasure in 
tiny ‘successes’ .
Brodzinsky et al.(3) identify the importance of adopters treading 
a ﬁ ne line between understanding and accepting the difference 
between parenting by adoption and parenting by birth, but not 
overemphasizing the difference.

Variables about placement practice and therapy
Few of the studies involving large enough numbers for statistical 
analysis look for statistically signiﬁ  cant associations between out-
come and placement practice or therapeutic interventions.
The child who remains for longer than a few weeks in temporary 
foster care is especially vulnerable to placement break down or 
moves made for bureaucratic reasons. Once settled in a planned 
long-term placement, when variables such as age at placement and 
behavioural difﬁ  culties are controlled for, break down rates for 
older-placed children are similar for children placed for adoption 
or in permanent foster families. Placements with relatives, and 
temporary foster placements conﬁ  rmed as permanent (through 
adoption, guardianship, or administrative decision), have been

adoption, guardianship, or administrative decision), have been 
found in most studies to have higher success rates that ‘stranger’ 
placements. Qualitative studies indicate that most children gain a 
sense of security from the legal status of adoption, but some can 
feel trapped and resentful, especially if they lose contact with birth 
relatives they want to see.(19, 20, 21, 23)
Chapters by US and UK researchers in a book on birth family 
contact(24) indicate that post-placement contact, in itself, does not 
adversely impact on the attachment process, and that it can help 
new parents and children to be more comfortable in talking about 
adoption issues. For children placed when older, remaining in face-
to-face contact with a birth parent, relative, or sibling, and being 
placed with a sibling, have been associated in several studies with

placed with a sibling, have been associated in several studies with 
more successful outcomes. However, this contact needs to be 
carefully managed and can sometimes be harmful to the child and 
to the stability of the placement.
The role of the psychiatrist
Child or adult psychiatrists will become involved in child place-
ment work because they are asked to provide therapy for a child, 
young person, or adult who has been placed for adoption or in fos-
ter care, or for a teenager or adult who has lost a child to adoption. 
Whether working with task-centred or permanent carers, the spe-
cial challenges of this different form of family life have to be 
acknowledged and incorporated into the therapeutic processes. It 
is for this reason that the need for specialist child mental health 
services for children in care or placed for adoption is now recog-

nized, which adapt the full range of effective therapeutic approaches 
to the special needs of the adoptive or foster family. Barth and col-
leagues(25) have noted that adoptive parents tend to pr efer attach-
ment-based therapies to the paren t-training approac hes that 
have been demonstrated to be effective with non-adoptive families. 9.3.5 the effects on child and adult mental health of adoption and foster care
Fig 9.3.5.1 Age at placement and percentage of placements disrupting. 
(Reproduced from J. Thoburn, Evaluating placement: survey ﬁ  ndings and 
conclusions. In Permanent family placement: a decade of experience  (eds. J. Fratter, 
J. Rowe, and J. Thoburn), pp. 34–57, copyright 1991, Brirish Agencies for Adoption 
& Fostering (BAAF), London.)

SECTION 9  child and adolescent psychiatry 1752
They hypothesize that in part this is because adopters believe that 
their special issues are better understood by the clinicians using these therapies, but they point to some potentially harmful effects of some of these methods, which can be experienced by the child as intrusive and coercive. Some clinicians who use attachment theories in their work also challenge the validity of some of these methods.
(26, 27)
Psychiatrists are often consulted about the advisability of adop-
tion or a return to the birth parents or relatives. The message from research is that adoption and foster care will be better for most chil-dren than being left with parents who can not be helped to provide them with safe and loving care. However, they are not without risks, which have to be carefully weighed for each child, and the ﬁ  rst step

must always be to try to improve the quality of parenting in the birth family. At ﬁ  rst sight, the break down rates for the placement of 
older children (now the majority of those needing placement) may appear discouraging. However, given their many difﬁ  culties, it 
should be welcomed that as many as 50 per cent of 11-year-old chil-dren, and more of those below that age, do ﬁ  nd permanent substi-
tute families. If permanent out-of-home placement does become necessary, the inherent risks demand the provision of the highest quality services provided for as long as needed.
For those who wish to pursue these issues in more depth look at references:
◆ 1, 2, 21, 22, 23 if you are providing therapy for a teenager or adult suffering the harmful effects of losing a child to adoption or foster care
◆ 7, 8, 10, 11, 12 on therapeutic and task-centred foster care
◆ 6, 9, 14, 15, 16, 17, 18, 19 to help with the decision-making process on substitute family placement options

◆ 2, 20, 21, 22, 23, 24 on birth family contact
◆ 3, 4, 14, 17, 21, 22, 25, 26, 27 on therapeutic approaches and methods when working with troubled children and their adop-tive or foster families.
 1. Carp, E.W. (2004). Adoption politics: bastard nation and ballot initiative 
58. Kansas University Press, Lawrence.
 2. Triseliots, J., Feast, J., and Kyle, F. (2005). The adoption triangle revisited. 
A study of adoption, search, and reunion experiences . BAAF, London.
 3. Brodzinsky, D.M., Smith, D.W., and Brodzinsky, A.B. (1998). Children’s 
adjustment to adoption: developmental and clinical issues . Sage, 
Thousand Oaks, CA.
 4. Rutter, M. (1999). Resilience concepts and ﬁ  ndings: implications for 
family therapy. Journal of Family Therapy ,21, 119–44.

 5. Bullock, R., Courtney, M., Parker, R., et al. (2006). Can the corporate 
state parent? Children and Youth Services Review ,28, 1344–58.
 6. Quinton, D. and Selwyn, J. (2006). Adoption: research, policy and 
practice. Child and Family Law Quarterly ,18(4), 459–77.
 7. Sellick, C., Thoburn, J., and Philpot, T. (2004). Success and failure in 
permanent family placement . Hants, Avebury, Aldershot.
 8. Sinclair, I. (2005). Fostering now: messages from research . Jessica 
 9. Thoburn, J. (2003). The risks and rewards of adoption for children in 
the public care. Child and Family Law Quarterly ,15(4), 391–402.
10. Wilson, K., Sinclair, I., Taylor, C., et al. (2004). Fostering success: an

10. Wilson, K., Sinclair, I., Taylor, C., et al. (2004). Fostering success: an 
exploration of the research literature in foster care . SCIE, London.11. T esta, M.F. and Rolock, N. (1999). Professional foster care: a future 
worth pursuing? Child Welfare ,LXXVIII (1), 109–24.
12. Fisher, P . and Chamberlain, P . (2000). Multi-dimensional treatment 
foster care. Journal of Emotional and Behavioural Disorders ,8(3), 155–64.
13. Festinger, T. (2002). After adoption: dissolution or permanence? 
Child Welfare ,LXXX1 (3), 515–33.
14. Rutter, M. and the English and Romanian Adoptees (ERA) Study T eam. 
(1998). Developmental catch–up and deﬁ  cit, following adoption after 
severe global early privation. Journal of Child Psychology and Psychiatry ,
39, 465–76.
15. Howe, D. (1997). Parent-reported problems in 211 adopted children. 
Journal of Child Psychology and Psychiatry ,38(4), 401–11.

16. Lindblad, F., Hjern, A., and Vinnerljung, B. (2003). Inter-country 
adopted children as young adults-a Swedish cohort study. The American Journal of Orthopsychiatry ,73, 190–202.
17. Rushton, A. and Dance, C. (2004). The outcomes of late permanent 
placements. Adoption & Fostering ,28(1), 49–58.
18. Thoburn, J. (1991). Evaluating placements: survey ﬁ  ndings and 
conclusions. In Permanent family placement: a decade of experience  (eds. 
J. Fratter, J. Rowe, and J. Thoburn), pp. 34–57. BAAF, London.
19. Selwyn, J. and Quinton, D. (2005). Stability, permanence and outcomes: 
foster care and adoption compared. Adoption and Fostering ,28(4), 6–16.
20. Thoburn, J., Norford, L., and Rashid, S.P . (2000). Permanent family 
placement for children of minority ethnic origin . Jessica Kingsley, London.

21. Beek, M. and Schoﬁ  eld, G. (2004). Providing a secure base in long-term 
foster care . BAAF, London.
22. Neil, E. (2003). Understanding other people’s perspectives: tasks for 
adopters in open adoptions. Adoption Quarterly ,6(3), 3–30.
23. Timms, J. and Thoburn, J. (2006). Y our shout! Looked after children’s 
perspectives on the Children Act 1989. Journal of Social Welfare and 
Family Law ,28(2), 153–70.
24. Neil, E. and Howe, D. (2004). Contact in adoption and permanent foster 
care: research, policy and practice . BAAF, London.
25. Barth, R.P ., Crea, T.M., John, K., et al. (2005). Beyond attachment 
theory and therapy: towards sensitive evidence-based interventions 
with foster and adoptive families in distress. Child and Family Social 
Work ,10(4), 257–68.
26. Dozier, M. (2003). Attachment-based treatment for vulnerable

26. Dozier, M. (2003). Attachment-based treatment for vulnerable 
children. Attachment and Human Development ,5, 253–7.
27. Prior, V . and Glaser, D. (2006). Understanding attachment and attachment 
disorders. Theory, evidence and practice . Jessica Kingsley, London.
9.3.6 Effects of parental 
psychiatric and physical illness on child development
Paul Ramchandani, Alan Stein, 
and Lynne Murray
A broad range of physical and psychiatric illnesses commonly affect

A broad range of physical and psychiatric illnesses commonly affect 
adults of parenting age. For example, approximately 13 per cent of women are affected by depression in the postnatal period, and the prevalence of depression in parents of all ages remains high. Many parents will also experience severe physical illness; breast cancer affects approximately 1 in 12 women in the United Kingdom, about a third of whom have children of school age. Worldwide HIV has an enormous impact on adults of parenting age. In some parts of sub-Saharan Africa up to 40 per cent of women attending antenatal

1753
clinics are HIV positive. Many of these parental disorders are associ-
ated with an increased risk of adverse emotional and social develop-ment in their children, and in some cases cognitive development and physical health are also compromized. It must be emphasized that a signiﬁ  cant proportion of children at high risk do not develop prob-
lems and demonstrate resilience,
(1) and, many parents manage to 
rear their children well despite their own illness. Nonetheless these risks represent a signiﬁ  cant additional impact and burden of adult 
disease (both physical and psychiatric) that is often overlooked.
This chapter reviews the current state of evidence regarding

This chapter reviews the current state of evidence regarding 
selected examples of psychiatric and physical conditions, from which general themes can be extracted to guide clinical practice. Some of the key mechanisms whereby childhood disturbance does or does not develop in conjunction with parental illness are consid-ered, and strategies for management and intervention reviewed.
Parental psychiatric illness
There is now reasonable evidence to suggest that most types of psy-chiatric disorder affecting parents are associated with an increased risk of difﬁ  culties for their children. There are some differences in risk 
by type of disorder; however, there are also some commonalities, sug-gesting that some of the mechanisms may be shared. Children’s disor-ders may resemble those of their parents
(2, 3) but there is also evidence

(2, 3) but there is also evidence 
of a much broader range of problems, including adverse effects on children’s social, emotional, cognitive and physical development. In the following section we will focus on parental depression, schizo-phrenia, eating disorders, alcoholism and substance abuse, and anxi-ety, but similar issues apply for other disorders not considered here.
Depression in either parent is associated with an increased risk of child psychopathology and other developmental difﬁ  culties, with 
the risks continuing into adulthood.
(3) The longest running longi-
tudinal study(4) found that, as well as a three-fold increase in major

tudinal study(4) found that, as well as a three-fold increase in major 
depressive disorder, the adult offspring of depressed parents had increased rates of anxiety disorders and substance dependence, as well as greater social impairment and physical health impairment. There has been a large body of research focusing on depression affecting mothers in the postnatal period, with studies demonstrat-ing that infants and children have an increased risk of emotional and behavioural problems.
(5) Some studies have suggested that 
children’s cognitive development may also be affected, although the results from studies are not consistent.
(6) Similarly, there is a 
suggestion that boys may be more affected than girls in early child-hood. As the children enter adolescence an increased risk of mood and anxiety disorders emerges.
(7) More recently research in devel-

oping countries has shown an association between postnatal depression and an increased risk of physical health problems in infants such as poor growth and diarrhoel illness.
(8)
Much less work has been done on depressed fathers, although 
consistent evidence is now beginning to emerge of an independent effect of paternal depression on children’s development.
(9) The 
overall impact may be less than that of maternal depression, and there are also conjoint effects to consider, as depression in one parent can often co-occur with depression or another psychiatric disorder in the other parent. Similarly there may be protective effects if one parent remains well.
(10)
While genetic factors clearly play an important role in the trans-
mission of risk from parents to children, environmental factors, and the interactions that occur between genetic and environmental fac-
tors, also have substantial inﬂ  uence.(11,12)  In the case of depression,

tors, also have substantial inﬂ  uence.(11,12)  In the case of depression, 
the core symptoms of low mood, loss of interest and low energy can have a signiﬁ  cant impact on parenting capacity and parent-child 
relations. These include a parent’s capacity to be responsive, consis-
tent, and warm when interacting with their children, particularly in the ﬁ  rst few years of life. For example, depressed mothers may be 
less vocal, less positive, and less spontaneous than controls, more negative, unsupportive, and intrusive, and have more difﬁ  culty in 
communicating and listening to their young children.
(13, 14)
Depression in either parent is strongly associated with marital 
discord.(15) This may play a key role in mediating the effects of 
parental depression and may be a more proximal predictor of child outcomes than depression.
(13) The way in which conﬂ  icts are

(13) The way in which conﬂ  icts are 
resolved may be very important and depressed parents are likely to use less effortful strategies, such as withdrawal. Children are gener-ally more at risk as they are exposed to an increased number of risk factors, and children whose parents are depressed are particularly at risk if they are also socio-economically disadvantaged.
The direction of effects is not all from parent to child, and tem-
peramental and behavioural factors in the child may also contribute to increasing family discord, parental psychiatric disturbance, and parenting impairments, and ultimately to disturbances in parent-child attachment. Infant irritability and poor motor control, mea-sured before the onset of any maternal depression at 10 days postpar-tum, increase the risk that a mother will become depressed.

(16) The 
inﬂ uence of parental depression on child development thus repre-
sents a complex bidirectional interaction between individual vulner-ability (which may be genetic), inﬂ  uences of depression on parenting 
characteristics, parent–child relationships, the wider context of the parental relationship, and other aspects of social disadvantage.
Parents with a diagnosis of schizophrenia have a greatly increased risk of having children who later develop schizophrenia themselves. Risks to child development are identiﬁ  ed from birth, with an 
increased likelihood of obstetric complications, not fully accounted for by maternal behaviour during pregnancy, or by genetic risk.
(17)
During childhood, prior to the onset of any psychiatric symptoms, attentional problems similar to those found in adult schizophrenic patients have been identiﬁ  ed and these problems not only persist 
into adulthood, but attentional problems have been identiﬁ  ed as

into adulthood, but attentional problems have been identiﬁ  ed as 
key neurobiological indicators of risk for subsequent schizophrenia or other psychopathology in adolescence and young adulthood.
(18)
Social difﬁ  culties with peers and teachers are found in many 
longitudinal studies of children with schizophrenic parents,(19)
although not necessarily to a greater extent than in children with parents suffering from affective disorder and a higher IQ can be protective. Social relationship problems and associated thought disorder may become more marked in adolescence and seem to be predicted by attentional problems.
(18) As young adults, children of 
schizophrenic parents are at high risk for schizotypal behaviour, although this broader range of difﬁ  culties does not necessarily 
distinguish them from parents with affective illness.
A pattern of disturbed communication has been described in fam-
ilies with a schizophrenic parent,
(20) but the importance of these

(20) but the importance of these 
interactions in explaining long-term outcomes has been questioned.
Overall, cognitive and attention difﬁ  culties appear to be largely 
associated with speciﬁ  c brain abnormalities linked with schizophre-
nia, but other kinds of childhood problems are probably inﬂ  uenced 9.3.6 effects of parental psychiatric and physical illness on child development

SECTION 9  child and adolescent psychiatry 1754
more by the general family disruption associated with a parent who 
requires hospital admission and who may have difﬁ  culties with 
employment and other social relationships beyond the family.
Eating disorders occur commonly among women of child-bearing age.
(21) Studies have raised concern that mothers’ attitudes and 
behaviours regarding food and body shape, may inﬂ  uence their 
children’s feeding, and ultimately the children’s own attitudes to body shape and eating.
(22) Children are particularly vulnerable at 
two stages of development—infancy and adolescence. During infancy feeding and mealtimes take up a signiﬁ  cant part of the day 
and provide important times for close communication between parents and children. A Scandinavian study has indicated that fail-ure to thrive may be a risk in the ﬁ  rst year amongst women with 
a history of anorexia nervosa.
(23) One controlled observational

(23) One controlled observational 
study of 1-year-old children of mothers with eating disorders found that the mothers were intrusive with their infants during both mealtimes and play, and they expressed more negative emotion and conﬂ  ict during mealtimes than controls, and allowed their children 
less autonomy.
(24) Furthermore, infant weight was independently 
and inversely related to mealtime conﬂ  ict.(25) Follow up studies of 
children of mothers who have experienced eating disorders in the postnatal period indicate that in middle childhood they are more likely than control children to value themselves by body shape and weight, and to use dietary restriction.
(22, 26)
During adolescence children become more aware of societal

(22, 26)
During adolescence children become more aware of societal 
pressures and develop increasing interest in body shape and  attractiveness while preoccupied with their own concerns about food, body shape, and weight. Children may model themselves on their parents, and parents may inﬂ  uence their adolescent children 
directly by expressing attitudes towards their children’s weight, shape, and eating habits. However, it should be emphasized that, in common with most parent psychopathology, the children of par-ents with eating disorders are not invariably adversely affected. Some parents manage well and their children develop without apparent problems.
Alcoholism and substance abuse
A substantial body of evidence has been amassed on the effects of parental alcoholism and substance abuse.
(27) They are wide 
ranging, identiﬁ  able throughout development, and work has high-
lighted the importance of the social effects on the child in addition to physical and psychological outcomes.

(28) Both genetic and envi-
ronmental factors seem to be involved.
The impact of maternal alcoholism on the developing child 
can be found from the prenatal period.(29) Present in 0.01 to 
0.03 per cent of normal births, foetal alcohol syndrome appears in 5.9 per cent of births of alcoholic women. There is also consider-able evidence that infants exposed prenatally to heroin and cocaine are at increased risk of a number of developmental difﬁ  culties 
which may persist throughout childhood.
(30)
Studies of outcome consistently describe impaired cognitive and 
social development in children of alcoholics and heroin users.(27, 30)

(30)
An increased risk of attention-deficit hyperactivity disorder, attention problems, and impulsivity in children of alcoholics is the most consistent ﬁ  nding. Children of drug abusers may also be more 
aggressive and have fewer friends and are at risk for criminality, depression, anxiety, and somatic problems. Children of alcoholics have an increased risk of becoming alcoholics themselves and, similarly, children of drug abusers also have an increased risk of 
drug abuse in adolescence, although many are resilient and do not develop similar problems themselves.
Social factors such as poverty and social isolation are known to 
inﬂ uence child development adversely and it has been difﬁ  cult to

inﬂ uence child development adversely and it has been difﬁ  cult to 
differentiate between the effects of the disorder and the associated adversity. Substance abuse in the parent may lead to impaired par-enting and an impoverished social environment, leaving children vulnerable to neglect or abuse and contributing to impaired social and cognitive functioning, psychopathology, substance abuse, and delinquency but the relative impact of each factor has yet to be resolved. Studies have identiﬁ  ed deﬁ  cits in parenting behaviour and, 
in particular, neglect and harsh discipline.
(31) Divorce and marital 
conﬂ ict are also more likely and there is evidence of assortative mat-
ing, all of which are likely to compound the risk for the children.
Stressful life events, and in particular those related to family con-
ﬂ ict, have proved to be important in accounting for the link

ﬂ ict, have proved to be important in accounting for the link 
between paternal alcoholism and alcohol use in their offspring.(32)
Overall, clinicians have emphasized a family perspective when conceptualizing the multiple levels of stress and vulnerability asso-ciated with parental alcoholism and opiate abuse and the need to enhance social supports for the family.
(30)
There is less information about children whose parents have anxiety disorders but there appears to be a considerable degree of speciﬁ  city in the familial transmission of anxiety disorder.
(33) One 
study showed a two-fold increased risk of anxiety disorders among offspring of parent probands compared with offspring of substance abusers or controls.
(34) However, they are also at risk of other kinds 
of problems such as depression.(35)
In a search for the mechanism of transmission, it has been

In a search for the mechanism of transmission, it has been 
suggested that children at risk for developing anxiety disorders have a temperamental vulnerability characterized by behavioural inhibition and autonomic reactivity, identiﬁ  able in infancy by 
an increased startle response.
(36, 37)  The question of the relative 
inﬂ uence of genetic or environmental factors does suggest a lesser 
genetic component for anxiety disorders,(38) and a developing line 
of research has led to a number of aspects of parenting behaviour of parents with anxiety being considered important, including over-protection and the limiting of children’s opportunities to develop new skills
(39). There appear to be some speciﬁ  c differences

(39). There appear to be some speciﬁ  c differences 
by type of anxiety disorder with, for example, mothers with social phobia demonstrating characteristic patterns of modelling of anxiety by the parent, and failure to provide encouragement/opportunities for child autonomy.
(40)
Recent lines of research have also explored possible risks in utero 
to the developing foetus. Children exposed to maternal anxiety in utero are at an increased subsequent risk of behavioral problems. This increased risk appears to persist through childhood, leading to suggestions that the mechanism may be in part mediated through an antenatal effect on the HPA axis of the developing foetus.
(41)
More research is needed to clarify the mechanisms but it is clear that children whose parents have anxiety disorders are at risk of developing psychiatric disturbance themselves.
Parental physical illness

Many families experience chronic parental illness and paradoxically, as treatment techniques improve illnesses may extend over longer time periods, which may have greater impact on family members

1755
including children. There have been limited reports about the 
impact of physical parental illness on children, however the impor-tance of this area is beginning to be recognized, particularly in relation to parental cancer, and also HIV .
(42) Similar associated 
difﬁ culties can arise with many other parental illness, particularly 
chronic ones such as diabetes. However we will here conﬁ  ne our 
comments to parental cancer and HIV , and the general issues that these conditions illustrate for the developing child.
Cancer
Parental cancer is likely to be associated with depression and marital difﬁ  culties, both risk factors for the child. The balance of 
evidence indicates that their children are at increased risk of devel-oping psychological disturbance.
(43) The impact of parental cancer

(43) The impact of parental cancer 
on family communication and child outcomes may vary according to the child’s developmental level, their gender, the presence of dis-ability in the child, and the parent’s level of psychological distress and marital discord.
(44)
A recent review(45) found that adolescents who had a parent with

(44)
A recent review(45) found that adolescents who had a parent with 
cancer had higher levels of emotional disturbance, than a normal population sample, but younger children were not consistently found to exhibit higher rates of problems, although some studies suggest this. Children’s own responses to their predicament are likely to affect their eventual adjustment. Problem-focused or active coping affects the stressors (e.g. seeking information, positive reinterpretation of stressful events) and is expected to be more adaptive while emotion-focused coping (e.g. venting emotions, denial, apathy) draws atten-tion away from the stressors but may place children at risk for anxi-ety and depression.
(46) Health professionals may need to assist 
parents in recognizing and coping with their children’s distress when it is present. Speciﬁ  cally, communication about the parental illness 
and how the children feel appears to be crucial to children’s cop-ing.

(47) The levels of anxiety and distress amongst the children are 
related to whether they are told about the illness and the quality of the communication with the parents, with informed children having lower levels of anxiety than those who are uninformed.
(44)
HIV status and AIDS
Women of child-bearing age account for an increasing number of sufferers of HIV/AIDS in the developing world and there is now increasing evidence that their children are at increased developmen-tal risk, even if the children are not HIV positive themselves.
(43)
Y oung children may have fewer problems(48) but those of school age 
are at risk for externalizing and internalizing problems, lower social skills, and academic achievement difﬁ  culties.
(49) Maternal depres-
sion is relatively common amongst women diagnosed with HIV during pregnancy,
(50) and the impact of this on their caregiving

(50) and the impact of this on their caregiving 
capabilities may be one of the key mechanisms by which children are affected. Given the enormity of the HIV pandemic and possible parallels with other common infectious diseases such as Malaria and TB, there is serious need for further research in this speciﬁ  c ﬁ eld.
Summary of mechanisms
Some of the key mechanisms by which increased risk for child dis-
turbance is transmitted from ill parents to their children have been described above. In cases of psychiatric disorder the link may in part reﬂ  ect genetic transmission, but clearly a considerable amount 
of the variance is accounted for by environmental mechanisms and a number of such mechanisms have been proposed.
(5,11) Most of

(5,11) Most of 
these can apply equally to parental physical or psychiatric illness. First, parental illness may interfere with parental functioning and parent-child interactions, for example where a parent becomes withdrawn or preoccupied and relatively unavailable to the child. Second, a number of family and environmental factors such as marital/family discord and severe housing or associated economic deprivation are associated with mental illness and these constitute risks in their own right, as well as sometimes being a direct conse-quence of the parental disorder (for example, parental depression leading to increased marital conﬂ  ict, although the reverse direction

of causality can also occur). Third, in rarer instances parental symptoms may impinge directly on the child, for example where the parent incorporates a child into the core symptomatology such as a delusion or an obsession. Finally, it should not be assumed that inﬂ uences are unidirectional. Child characteristics such as early 
temperamental difﬁ  culties or behavioural problems may inﬂ  uence 
the outcome of parental illness, particularly in the case of depres-sion.
(3) Child characteristics such as coping style, intellectual
ability, or sociability may be particularly important in explaining resilience.
Implications—responding to a parent in 
clinic and preventive interventions
As the inﬂ  uences of parental illness on children’s development

As the inﬂ  uences of parental illness on children’s development 
become better understood there is increasing recognition of the potential importance of addressing parent-child links. This is both in making better enquiry about child welfare when a parent is seri-ously ill, but also enquiring about parental health when a child presents with a disorder such as depression (e.g. NICE guidance on depression in children and young people
(51)) Two particular areas 
will be considered here; when a parent presents with a serious ill-ness (psychiatric or psychological) and potential intervention strat-egies with high-risk groups who may or may not be presenting to health services.
When parents with serious physical or psychological illness are

When parents with serious physical or psychological illness are 
seen as outpatients, especially if they are subsequently admitted to hospital, it should be routine to enquire about children—their ages, developmental and scholastic progress, child care arrange-ments, and family support. In the limited time available, it makes most sense to enquire about the areas most likely to be affected by the parental disorder.
(52) For example, where a parent with 
depression has young children, enquiry could focus on the level of care that the parent feels able to provide to the children, the feelings that the parent has for their children, and the presence of any marital or family discord, as well as the available support. These questions obviously require sensitive handling, as parents can easily feel blamed for any effect that they perceive their illness may have had on their children. In many cases provision of appro-priate support and treatment to the parent will have a sufﬁ  ciently

beneﬁ  cial effect for the whole family that no further intervention 
is required, (for example, ﬁ  ndings from a recent large random-
ized controlled trial identify improvements in children’s out-comes when their mother’s depression is treated.
(53)) However it 
is crucial to ask and make at least this preliminary assessment. Close collaboration with the primary care team, including the family’s general practitioner, is of considerable importance. The general practitioner’s involvement may be critical, both in terms of potential treatment and support for the family, and also as a 9.3.6 effects of parental psychiatric and physical illness on child development

SECTION 9  child and adolescent psychiatry 1756
source of knowledge of the wider family system, and the resources 
available to the family.
In those cases where a child is more severely affected (either 
directly by a parent’s illness or by other related factors), consider-ation should be given to including relevant children’s services, either Child and Adolescent Mental Health Services (CAMHS) or children’s care services. Close collaborative relationships between child and adult mental health services clearly ease potential joint working, and should be the norm. Communication with, and the close involvement of, the family’s general practitioner, can also contribute to a plan to beneﬁ  t the whole family system.
In those cases where a parent has a chronic illness and the clini-

cian gets to know them over a period of time, it can be helpful to ask about children’s understanding and knowledge of the parental illness and the extent to which it has been discussed within the fam-ily. These issues will need to be carefully and sensitively handled. Families have a range of ways in which they communicate and it is important not to compound the parent’s problems by making them feel their illness is harming their children. As far as inpatients are concerned, it is important that facilities should be available for chil-dren visiting and, unless speciﬁ  cally contraindicated, regular con-

tact should be encouraged, and appropriate play and other materi-als should be available. Discussions should be held with the patient and/or relatives about child-care arrangements, and the patient and family need to be helped to think about providing the child with an appropriate explanation about parental health and absence.
Communication either about the parental illness or the associ-
ated discord may help to alleviate some of the risks for childhood 
problems.
(44) Studies of marital disruption and divorce have found 
that children cope better with marital conﬂ  ict when they are given 
some explanation or told that the conﬂ  ict has been resolved.(54)
Children often feel left out and, without knowledge of the parental 
illness, they may be particularly likely to attribute any family conﬂ  ict or disruption to themselves in their effort to understand

illness, they may be particularly likely to attribute any family conﬂ  ict or disruption to themselves in their effort to understand 
the changes taking place. Intervention, including working with family communication, can have signiﬁ  cant positive effects if well 
handled. Some guidelines are available.
(55,56)
Less work has been conducted in families where the parent 
is physically ill, although reports of treatment once the family members are experiencing problems are providing some ways forward.
(45) Parents may consciously avoid disclosure because of 
the questions they anticipate from their children, particularly about death. Communication in this context is not only a matter of dis-closure of the illness but a starting point for ongoing discussion and questions, without which children may be at increased risk.
(57)

(57)
The most important role of support services may be to rehearse with parents the kinds of questions that might occur and how they could respond, a strategy which may also facilitate discussion of the ill parent’s anxieties.
Beyond the scope of the individual parent and family in clinic there have been a number of studies which have examined the possibility of preventative intervention in high-risk groups. This is most often conducted in the context of parental depression. One series of intervention studies with children of parents with major depres-sion has shown marked improvement in family functioning and child outcome.
(58) These interventions have taken a variety of for-
mats, but all include a component of psycho-education directed to the whole family. However, in another trial, the involvement of par-
ents in a group programme for adolescent offspring of parents with depression did not show any additional beneﬁ  t.

Some preventive intervention can clearly be accomplished earlier. 
In infancy it is possible to promote the development of secure par-
ent–child attachment, which should be protective even if the paren-tal illness is chronic. Maternal sensitivity can be enhanced using videotaped mother-child interactions, which can increase the rate of secure attachment in at-risk families.
(59) In the case of maternal 
eating disorders there is now some encouraging evidence for the effectiveness of video feedback treatment to enhance maternal responsivity to the infant, and to decrease mother-infant conﬂ  ict.
(60)
A recent review of treatments for mothers and infants in the context

(60)
A recent review of treatments for mothers and infants in the context 
of maternal depression found that treatment of maternal depres-sion alone did not appear to mitigate the impact of the depression on the child. However, a number of different mother-infant psycho-therapies did appear to confer beneﬁ  t on mother child interaction 
and child outcome. However, much work remains to be done.
(61)
In conclusion, children of parents with physical or psychiatric illness are at risk of a wide range of developmental and psychiatric difﬁ culties, although not all will develop problems. Future work 
should be directed to developing and evaluating ways of providing support so that parents can best manage their illnesses and to prevent or mitigate any negative effects on their children.
The SCIE parental mental health network (www.scie.org.uk/mhnetwork/
resources.asp)
The Children of Parents with a Mental Illness (COPMI) (www.aicafmha.

net.au/copmi/index.html)
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9.3.7 The effects of 
bereavement in childhood
Bereavement is not an illness in itself, although it may cause illness 
or predispose to one. The reaction to the loss of a loved one may lead to temporary or long-term psychological distress and/or loss of function, and may occasion consultation with the general prac-titioner and referral to mental health professionals.
During the ﬁ  rst two years of life, through instinctive behaviours

During the ﬁ  rst two years of life, through instinctive behaviours 
which are modiﬁ  ed by experience, infants and their main carers 
develop an attachment. This bond between a child and his caretaker(s) ensures the child’s survival, enables his or her optimum physical, intellectual, and emotional development, and in due course ensures the survival of the species. The nature of the attachment between infant and carer(s) inﬂ  uences the way in which 
children come to view their social world; the pattern of attachment developed in the ﬁ  rst two years of life often remains stable and is 
associated with the way in which children relate to other people 
later in their life. Attachment behaviour has been observed across different species and has obvious beneﬁ  ts for survival. However,

later in their life. Attachment behaviour has been observed across different species and has obvious beneﬁ  ts for survival. However, 
part and parcel of attachment for the child is distress at separation. Infants who develop a secure attachment can gradually tolerate lon-ger periods of separation from their carer and any distress is rapidly assuaged when they are re-united with their carer. When considered within the context of attachment theory, it is inevitable that perma-nent separation (e.g. through bereavement) will cause distress for the bereaved. Parkes reviews the body of attachment research and offers a comprehensive description of attachment with particular reference to its role in understanding the impact of loss.
(1)
The DSM-IV-TR has a classiﬁ  cation for ‘Bereavement’ (V62.82) 
differentiating it from ‘Major depressive disorder’ (296.2) which, unless the symptoms are severe, is generally not diagnosed until 2

differentiating it from ‘Major depressive disorder’ (296.2) which, unless the symptoms are severe, is generally not diagnosed until 2 
months after the loss. ICD-10 has no separate classiﬁ  cation for 
bereavement and suggests the use of ‘Adjustment disorders’ (F43.2) for temporary reactions to life-events, and ‘Death of a family mem-ber’ (Z63.4) for normal bereavement reactions not exceeding 6 months in duration.
In industrialized countries between 1.5 and 4 per cent of chil-
dren are orphaned of at least one parent in childhood. Premature deaths in the parenting years may be due to illness, accident, war, civil conﬂ  ict, natural and man-made disasters and the incidence of 
these are all higher in developing countries. It is estimated by UNICEF that, in some developing countries, 21 per cent of chil-dren are orphaned of at least one parent; with HIV AIDS respon-sible for up to three-quarters of the deaths.
(2)

(2)
Reactions to the death of a parent
Research studies
It is generally accepted that loss of a parent in childhood is associated with harmful psychological consequences, however it is difﬁ  cult to 
tease out the independent effects of adverse circumstances before the death, the loss itself and the subsequent disruption to the child’s life, including the possibility of compromized parenting post-bereave-ment
(3,4). Most published research about bereaved children describes

(3,4). Most published research about bereaved children describes 
small-scale uncontrolled studies carried out on children and adoles-cents referred to mental health facilities. Dowdney comprehensively reviews the research examining the psychological impact of being bereaved of a parent in childhood. She concludes that despite meth-odological weaknesses, certain findings consistently emerge: ‘Children do experience grief, sadness, and despair following paren-tal death. Mild depression is frequent, and can persist for at least a year after parental death’ . Bereaved children commonly exhibit a range of psychological symptoms that may not constitute a speciﬁ  c 
disorder, but the severity of which is likely to warrant referral to a specialist service for one in ﬁ  ve bereaved children.
(5)
Long-term effects of bereavement
There continues to be debate about a possible link between being

(5)
There continues to be debate about a possible link between being 
bereaved of a parent as a child, and mental health as an adult. The debate is complicated by methodological weaknesses in stud-ies, inconsistent results and difﬁ  culty in isolating the impact of 
experiences which may precede or follow the loss. Any long term 
consequences of parental bereavement can be mitigated by the sub-
sequent provision of adequate parenting
(6, 7). Furthermore, studies 
in behavioural genetics are increasing the understanding of how 
genetic endowment interacts with environmental hazards to lead 
to the presence or absence of mental health problems.(8)
Cultural and religious issues
Reactions to loss are biologically based and are therefore likely to transcend cultural differences, although culture may modify their expression.
(3) Religious beliefs about what happens after

(3) Religious beliefs about what happens after 
death can be confusing to young children at the stage of concrete thinking and need to be presented taking account of their develop-mental stage. A helpful text
(9) gives guidance on religious and 
cultural differences in the conceptualization of death.
Developmental issues
Y oung children react to the absence of a parent by developing an anxiety or depressive reaction, often expressed somatically (regression

1759
in acquired control, anorexia, insomnia), but young children can-
not distinguish temporary from permanent loss(3,10) . Research 
consistently demonstrates that children ordinarily do not develop a full understanding of the concepts of death before the age of 7 years, although younger children of 4 years and above can under-stand it with appropriate help.
(11)
Pre-pubertal schoolchildren can be helped more easily to 
comprehend the reality of death, especially if they are given an opportunity to see for themselves the cessation of function. In cultures where viewing the body is the norm, there may be fewer misconceptions about death among children, but this should not be undertaken where the body is mutilated.
(12) Although difﬁ  cult 
to substantiate scientiﬁ  cally, clinical literature suggests that attend-
ing the funeral helps the grieving process.(5)
For adolescents the death of a parent may come at a time when

For adolescents the death of a parent may come at a time when 
they are freeing themselves from dependence and may have been in conﬂ  ict with the parent who subsequently dies, leaving the young 
person with feelings of guilt and anger. Suicidal feelings are more likely to be acted upon if part of a depressive reaction. Adolescents are more able to sustain sad affects and express grief directly, but they may also react with behavioural and academic difﬁ  culties.
The reader is referred to Dyregrov for a more comprehensive 
description of common reactions to bereavement in childhood.
(13)
Children and adolescents with learning difﬁ  culties may be at 
higher risk for developing psychological problems following bereavement, because of their cognitive difﬁ  culty in understanding 
the components of the concept of death and because of their greater dependency.

(14) Everatt and Gale provide a helpful review of the 
available research and draw implications for bereaved children with learning disabilities.
(15)
Traumatic bereavement
As with adults, children who witness horriﬁ  c events involving the

(15)
As with adults, children who witness horriﬁ  c events involving the 
death or severe injury of people close to them, or upon whom they are dependent, are at risk of developing post-traumatic stress dis-order (see Chapter 9.3.2). Traumatic symptomatology can impede the resolution of grief through mourning as for mourning to pro-ceed, the child has to summon up an image of the dead person. However, if when she/he tries to imagine the deceased, a frighten-ing picture appears or she/he experiences again the helplessness or terror he felt at the time of the death, she/he will tend to avoid recalling the person and thus will not be able to grieve for her/him. Similarly, children whose parents die through suicide or homicide are more likely to have difﬁ  culties. In such cases, not only is the 
nature of the death traumatic and more difﬁ  cult to make sense of,

nature of the death traumatic and more difﬁ  cult to make sense of, 
but there is often an unhelpful media interest and, social support 
systems that would ordinarily be available may ﬁ  nd the circum-
stances of the death unbearable. If there is a body at all it may be disﬁ gured or its release to the relatives may be delayed the investi-
gation or the authorities and mementoes or suicide notes may be retained by the authorities. Children who have been traumatized by experiencing the sudden, violent, or horriﬁ  c death of someone 
close to them are unlikely to beneﬁ  t from bereavement counselling 
or therapy until the post-traumatic stress symptoms have been treated
(16,17) .
Other losses
Much of our knowledge of the impact of bereavement on children and young people is drawn from research on children bereaved of a parent. Other losses have been less well studied; however reactions may be similar depending upon the relationship between the child

and the deceased. The death of a grandparent, particularly if he or she lived with the child or carried out caretaking functions, can be devastating to child and parents. Sibling death carries a high mor-bidity for the survivors, but this can be mitigated by preparation for the death when possible and by participation in community rituals.
(18) Adolescents losing a sibling often deny the ﬁ  nality and 
universality of death, even when these concepts are well established prior to the death.
(19) The losses of friends, of pets, or of homes, 
whilst eliciting sadness, are less likely to provoke pathological grief reactions provided that the child is supported by parents and other adults who are not themselves withdrawn in grief. However, adolescents are affected by the suicide of a friend. A controlled study found that there was a higher incidence of depression than in a matched population sample, although the incidence of attempted suicide was no higher.
(20)

(20)
Many of the adverse sequelae of childhood bereavement can be modiﬁ  ed or prevented by an intervention before the death or 
shortly afterwards. In a controlled study, a brief family intervention 2 months after the death of a parent signiﬁ  cantly reduced children’s 
morbidity at 1 year post-bereavement. The differences between the treatment and the control group were no longer signiﬁ  cant at 
2 year follow up, but some of the more affected children had been lost to follow-up, making comparison difﬁ  cult. But even if by 
2 years the effect of the intervention is no longer signiﬁ  cant, there 
is an argument for intervening to relieve symptoms and reduce suf-fering in the short and medium term.
(21) Schut & Stroebe’s most

(21) Schut & Stroebe’s most 
recent review concludes that, although in the general adult popula-tion a bereavement intervention is more effective for those with more complicated grief reactions, ‘children are likely to be a special case, perhaps beneﬁ  ting from primary intervention.’ (A primary 
intervention is one which is open to all bereaved people rather 
than targetted at those who are at risk of difficulties such as following traumatic death, or those experiencing complicated reactions.).
(22)
Children whose symptoms reach the threshold for a diagnosable psychiatric disorder require a careful clinical assessment to determine the most appropriate treatment, and other sections detail the appropriate interventions for disorders such as depres-
sion (Chapter 9.2.7), anxiety (Chapter 9.2.6) or Post-traumatic Stress Disorder (PTSD: Chapter 9.3.2). Some studies have found

sion (Chapter 9.2.7), anxiety (Chapter 9.2.6) or Post-traumatic Stress Disorder (PTSD: Chapter 9.3.2). Some studies have found 
that parents report fewer symptoms in their bereaved children than the children do themselves; this means that it is important in research and clinical practice to interview the children individually if possible.
(5)
Children bereaved of a carer urgently need to be looked after and 
will transfer their attachment to a new caretaker who is available for them and responsive to them. Supporting a widowed parent in 
his or her grief, and enabling the process of mourning to occur by 
providing practical help (child care, ﬁ  nancial advice, etc.), may be 
as important as counselling in helping the children. It may be also 
appropriate to offer support, supervision and guidance to other 
adults involved in the child’s life such as teachers and religious leaders.
The therapeutic elements of appropriate interventions include

The therapeutic elements of appropriate interventions include 
the promotion of communication within the family about the dead 9.3.7 the effects of bereavement in childhood

SECTION 9  child and adolescent psychiatry 1760
parent, the promotion of mourning through reminiscing, the 
appropriate expression of feelings, and making sense of the death. An overview of techniques used directly with children and young people is provided by Stokes.
(23) T echniques for use with children, 
many of which can be done in groups, include:
◆ Using art and story-telling
◆ Writing letters to the deceased
◆ Creating memory boxes to store reminders of the deceased
◆ Rituals (such as lighting candles, releasing balloons)
◆ Making something that represents different aspects of the person 
(e.g. salt statues of different colours)
◆ Playing games which encourage children to open up
◆  Role playing
As with all direct interventions with children, the choice of which

As with all direct interventions with children, the choice of which 
techniques to use depends upon the child factors such as age and intelligence, the therapist’s or counsellor’s training, skill, and experience, the nature of the therapeutic relationship and the orga-nizational context. These interventions can be provided by care-fully selected, well-trained and well-supervized volunteers. As part of an intervention, young children may require help to understand what has happened to the deceased by offering a careful and sensi-tive explanation of what death means in straight-forward biological terms ensuring that the child understands what they are being told. They may also need help to recognize, understand and cope with sad affects both in themselves and in the surviving family members.
Given the indications that problems may develop much later,

Given the indications that problems may develop much later, 
a useful intervention strategy should include follow-up appoint-ments after any time-limited intervention. Children who have been prepared for the death of a family member have been shown to fare better, in terms of anxiety levels, than those who have not.
(24)
Bereavement in childhood, particularly the loss of a parent, repre-sents a signiﬁ  cant adversity, although the majority of bereaved chil-
dren do not develop anything other than transient symptoms. Nevertheless, there is evidence that a brief preventive intervention can reduce subsequent morbidity. Children, who lose a parent through suicide, homicide, accident, or disaster, especially if they have witnessed the death, are at high risk of developing post-trau-matic stress disorder and other psychiatric disorders and their treatment needs should be assessed by mental health professionals.

Dyregrov A (1991). Grief in children: a handbook for adults . London, Jessica 
Kingsley Publishers.
Cohen JA, Mannarino AP , Deblinger E (2006). Treating Trauma and 
Traumatic Grief in Children and Adolescents . New Y ork, The Guilford 
Press.
Various useful resources for professionals, parents, carers and bereaved 
young people and children are provided by the UK child bereavement charities: The Child Bereavement charity (www.childbereavement.org.uk) and Winston’s Wish (www.winstonswish.org.uk).
Help is at Hand: A resource for people bereaved by suicide and other 
sudden, traumatic death.  This booklet is published by the National 
Health Service in the UK, and provides particularly good advice for parents of suddenly bereaved children. www.dh.gov.uk/
assetroot/04/13/90/07/04139007.pdf
 1. Parkes, C.M. (2006). Love and Loss: The Roots of Grief and its 
Complications . London and New Y ork, Routledge.

 2. UNICEF (2006). Africa’s Orphaned and Vulnerable Generations: 
Children Affected by AIDS . Geneva: UNICEF, UNAIDS and PEPFAR.
 3. Bowlby, J. (1980). Attachment and Loss . London, Hogarth Press.
 4. Rutter, M. (1972). Maternal Deprivation Reassessed . Harmondsworth, 
Penguin.
 5. Dowdney, L. (2000). Annotation: Childhood Bereavement Following 
Parental Death. Journal of Child Psychology and Psychiatry, 41,
819–30.
 6. Harrington, R. (1999). Unproven assumptions about the impact of 
bereavement on children. Journal of the Royal Society of Medicine, 92,
230–3.
 7. Bifulco, A., Harris, T., and Brown, GW. (1992). Mourning or early 
inadequate care? Re-examining the relationship of maternal loss in childhood with adult depression and anxiety. Developmental 
Psychopathology, 4, 433–49.

 8. Lau, J.Y.F., Rijksdijk, F.V ., Gregory, A.M., et al.  (2008). Pathways to 
childhood depressive symptoms: The role of social cognitive and 
genetic risk factors. Developmental Psychology ,43, 1402–14.
 9. Parkes, C.M., Laungani, P ., and Y oung, B. (eds.) (1997). Death and 
bereavement across cultures . London, Routledge.
10. Furman, E. (1974). A child’s parent dies . New Haven, CT, Y ale University 
Press.
11. Slaughter, V . (2005). Y oung children’s understanding of death. 
Australian Psychologist, 40(3), 179–86.
12. Cathcart, F. (1988). Seeing the body after death (editorial). British 
Medical Journal, 297, 997–8.
13. Dyregrov, A. (2008). Grief in children: a handbook for adults (2nd edn) .
14. Kloeppel, D., and Hollins, S. (1989). Double Handicap: mental

14. Kloeppel, D., and Hollins, S. (1989). Double Handicap: mental 
retardation and death in the family. Death Studies, 13, 31–8.
15. Everatt, A., and Gale, I. (2004). Children with learning disabilities 
and bereavement: A review of the literature and its implications. Educational and Child Psychology, 21(3), 30–40.
16. Cohen, J.A., Mannarino, A.P ., and Deblinger, E. (2006). Treating 
Trauma and Traumatic Grief in Children and Adolescents . New York, 
The Guilford Press.
17. Harris-Hendriks, J., Black, D., and Kaplan, T. (2000). When Father Kills 
Mother .Second edition . London, Routledge.
18. Pettle, M.S., and Lansdown, R. (1986). Adjustment to the death of a 
sibling. Archives of Diseases of Childhood, 61(3), 278–83.
19. Hogan, N., and DeSantis, L. (1996). Adolescent sibling bereavement. In 
Handbook of adolescent death and bereavement  (eds. C. Corr, D. Balk),

Handbook of adolescent death and bereavement  (eds. C. Corr, D. Balk), 
pp. 173–95. New Y ork, Springer.
20. Brent, D., Perper, J., Moritz, G., et al. (1992). Psychiatric effects of 
exposure to suicide among the friends and acquaintances of adolescent 
suicide victims. Journal of the American Academy of Child and 
Adolescent Psychiatry, 31, 629–39.
21. Black, D., and Urbanowicz, M.A. (1987). Family intervention with 
bereaved children. Journal of Child Psychology and Psychiatry, 28,
467–76.
22. Schut, H., and Stroebe, M. (accepted for publication). Interventions to 
Enhance Adaptation to Bereavement: A Review of Efﬁ  cacy Studies. The
Lancet.
23. Stokes, J.A. (2004). Then, now and Always . Cheltenham, Winston’s 
Wish.
24. Rosenheim, E., Reicher, R. (1985). Informing children about a parent’s 
terminal illness. Journal of Child Psychology and Psychiatry, 26,
995–8.

In the last 20 years, many societies have paid greater attention to 
children’s rights and the importance of protecting children from abuse. As perpetrators of abuse have been tried in court, so more children have been called as witnesses. From being described as ‘the most dangerous of all witnesses’ , children have become recognized to be able to provide valuable and credible testimony in the correct circumstances. Many jurisdictions are now making allowances for children so that their testimony can be delivered in court as fully and accurately as possible. It is no longer tenable to dismiss the capacity of a child to be a witness in court simply because of their age. Children may be less reliable, as reliable, or more reliable 
than adult witnesses, depending on a variety of developmental and environmental factors .
Developmental considerations for children 
as witnesses
Memory is immature below the age of 12

In the ﬁ  rst 3 years of life recall is via preverbal memory (sometimes 
called eidetic memory), which allows early events to be recalled visually but not in words. Preverbal memory is very accurate but is largely lost around the age of 3 years as language develops. This form of memory remains longer in children who have delayed lan-guage development. The loss of this early form of memory explains why adults do not usually have conscious memories from the 
ﬁ rst 3 years of life . It is only around the age of 3 years that experi-
ences begin to be memorized in ‘explicit memory’ , which is accessed by verbal recall.
(1) Memories laid down in explicit memory are

(1) Memories laid down in explicit memory are 
organized according to hierarchical cognitive structures formed by the child’s past experiences of the world. In young children, this organization is rudimentary. This means that new memories are stored with little selection or adaptation to reﬂ  ect preconceptions, 
and in younger children the retrieval of stored memories from 
poorly organized mental representations is difﬁ  cult . External 
prompts and cues help children recall more fully but in court  witnesses are not generally allowed to be ‘led’ by questioning. Y ounger children are more likely than older children to forget 
information over time. By the age of 12 years, children are gener-
ally considered to have the same capacities to lay down memories and recall information as adults .
Surprisingly, children’s immature memories can sometimes

Surprisingly, children’s immature memories can sometimes 
actually improve the quality of information provided in witness statements . For example, events may be memorized without being 
inﬂ uenced by the prejudices that affect adult perceptions, and 
seemingly trivial details may be memorized by a child whose prim-itive cognitive schemas allow incoming sensory information to be memorized unselectively.
(2) However, cognitive immaturity more 
often acts as a barrier to children giving their testimonies fully and accurately , especially when they are asked to talk about what 
they remember, rather than being allowed to communicate by behaviour or play.
Children’s expectations of adults in conversation 
inﬂ uence testimony
By the age of 6 years, many children are using the syntax and gram-

mar of adults in their spoken language. However, their vocabulary is still limited and they are easily confused by sophisticated or 
complex speech . A particularly important aspect of language 
development for child witnesses is the role played by children and adults in conversational partnerships. Children are used to being 
co-operative partners when talking with adults . They attempt to 
please by providing answers to questions, even if they do not know the answer or have not understood the question.
(3) Y oung children

(3) Y oung children 
rarely answer ‘I don’t know’ to a question they are uncertain about and prefer to give a false ‘yes’ or ‘no’ . This willingness to provide an answer is probably encouraged by the frequent experience of being ‘tested’ by adults who already know the answers to the question (for example, ‘Look at this picture! Can you see the duck?’ or ‘How many sweets am I holding?’). As children expect adults to know the answers to their questions, and if a question is repeated, children may change the answer they gave in the assumption that the questioner feels it to be wrong. The readiness of young children to please adults in 
conversation no doubt adds to their suggestibility.9.4
The child as witness

SECTION 9  child and adolescent psychiatry 1762
Young children are particularly suggestible
The suggestibility of children as witnesses has been a major concern 
in legal arenas. Modern research does not endorse the stereotype of the child witness as being highly suggestible. However, there is clear evidence that both children and adults are prone to suggestion at times, and that pre-school children are particularly vulnerable to 
this. The necessity to avoid suggesting information or answers to a 
child has led to the development of guidelines for interviewing child witnesses in several jurisdictions.
Immature moral development is not always a problem

According to Kohlberg’s seminal description of children’s moral development, children below 10 years of age operate with ‘pre-conventional morality’ and evaluate events according to whether the child themselves will gain reward or avoid punishment. Only after this age do children develop ‘conventional morality’ and begin to be motivated by the approval of other people and society. Therefore, only older child witnesses have a full understanding 
of their moral obligations in court . However, young children, 
who may hold concrete worldviews such as ‘bad people must be punished’ as moral imperatives, may be strongly motivated to tell the truth in court.
Children do not lie more than adults, but their lies are 
more easily detected
Contrary to popular belief, children above the age of 3 years have

Contrary to popular belief, children above the age of 3 years have 
no more difﬁ  culty than adults in distinguishing fact from fantasy. 
Neither do children tell more lies than adults (although children’s lies are more often unconvincing and therefore more easily discov-ered). Children and adults are motivated to lie for similar reasons .
(4)
The two motives for lying, which may particularly influence 
child witnesses asked to testify in cases of child abuse, are fear of personal recrimination and a wish to protect those to whom a child feels loyal.
Immature sense of time and short attention span 
Before 8 years of age, children do not generally have a clear sense 
of time . Y oung children therefore often have a muddled recollec-
tion of the timing of events and they may have difﬁ  culty saying 
how many times an event occurred. Similarly, children below this

how many times an event occurred. Similarly, children below this 
age have short attention spans , and readily become bored or over-
whelmed by prolonged questioning. Both of these developmental limitations can cause difﬁ  culties in the preparation of witness state-
ments when a child appears in court.
Traumatic memories may be recalled with more or less 
clarity
Many of the events child witnesses are called upon to remember 
were unpleasant and frightening at the time. These events will have been experienced in a state of high emotional arousal. Clinical experience suggests that emotional arousal can either enhance or 
diminish recalled information . For example, extremely traumatic

diminish recalled information . For example, extremely traumatic 
events such as watching a parent being killed can be remembered by child witnesses in a series of highly accurate and detailed visual images that persist in memory over time. By contrast, some chil-dren process potentially overwhelming experiences using a variety of psychological defense mechanisms, which limit the amount and accuracy of material available in explicit memory. The psychologi-
cal trauma associated with the witnessed event and the emotional state of the child during subsequent recall are both likely to have an inﬂ uence on a child’s capacity to give evidence in court.
Environmental considerations for children 
Skilled interviewing is essential
Because of their developmental immaturity, child witnesses face

Because of their developmental immaturity, child witnesses face 
many disadvantages in the legal system, but these can be substan-tially offset by a skilled interviewer. Not only must an interviewer facilitate a child to say as much as he or she can remember, but the interview must be conducted so that its process and content will be considered to be acceptable evidence by the court.
(5) Psychological 
research guides the practice of interviewing child witnesses. Some principles are outlined in Table 9.4.1.
Helpful adjustments to legal standards and courtroom 
process
Many jurisdictions have now made allowances for the developmen-
tal and emotional needs of children appearing in court as witnesses. Some legal systems have relaxed their rules of evidence  where

tal and emotional needs of children appearing in court as witnesses. Some legal systems have relaxed their rules of evidence  where 
children are concerned so that hearsay evidence (in other words, reports from other people about what a child said or did) may be admissible and lawyers may be allowed to ask child witnesses lead-ing questions. The detrimental effect of extreme stress on children’s abilities to give accurate and credible evidence in court is well recognized. A variety of actions have therefore been taken by courts to make a child witness’s appearance in court less stressful. The courtroom may be rearranged to be less formal  and professionals 
may not wear gowns or wigs. The public may be excluded from courtrooms. Means of preventing the child from having to face 
the accused  such as the use of screens or a live video-link to the 
child in a separate room may be used. Although many professionals

child in a separate room may be used. Although many professionals 
agree that children generally ﬁ  nd giving evidence by video-link less 
stressful than giving their entire evidence in open court, there is concern that the child’s testimony may have less impact on a jury when viewed on video.
(6)
Child witnesses need extra support in the courtroom
There is no doubt that children ﬁ  nd appearing in court a stress-
ful event . Typical concerns of child witnesses are shown in 
Table 9.4.2. Feelings of anxiety, confusion, humiliation, embarrass-ment, and the fear of retaliation or of not being believed Table 9.4.1  Guidelines for interviewing child witnesses
◆  Allowing a child to talk freely without being questioned maximizes the 
chances of accurate recall
◆ Questioning children may elicit additional information but lessen accuracy
◆  Accuracy is greatest when children give their statements as soon as an event

◆  Accuracy is greatest when children give their statements as soon as an event 
occurred
◆  Children’s accounts are most likely to be accurate when they tell the story for the ﬁ  rst time
◆  Children are less likely to give a full account if they feel under pressure from the interviewer
◆  Younger children may attempt to please an interviewer by providing information even if it is untrue

1763
are common. The stress of appearing in court may be a further 
trauma for a child who was ﬁ  rst traumatized by witnessing or expe-
riencing the alleged crime in question. Some children report that although giving evidence was stressful, they also derived some satis-faction from playing their part in bringing a perpetrator to justice.
Anxiety created by the unfamiliarity of the surroundings and a 
lack of knowledge about what is happening in the courtroom can be addressed by preparing child witnesses for their appearance in 
court . Preparation often involves visiting the courthouse, receiving 
age-appropriate written information about the court process, and having the opportunity to ask questions. Ideally, the professional who prepares the child should be available to attend court with the child on the day of the trial. Some helpful information for child witnesses is shown in Table 9.4.3.
Receiving therapy prior to being a witness

Many child witnesses have been traumatized by witnessing or experiencing the alleged crime to which they will testify. Some of these children will develop emotional or behavioural problems as a result of the trauma and will be referred to child and adolescent mental health services. Treatment of trauma-related symptoms usually involves recounting the past experiences in a therapeutic setting. At this point a conﬂ  ict of interests arises between the 
needs of the child as a patient and as a witness . The psychothera-
peutic treatment of traumatized children centres on eliciting the child’s subjective truth by the therapist using a variety of means to encourage communication. Within the legal system, the child’s rec-ollection of events must be examined in a neutral setting to deter-mine the objective truth, while the rights of both the accused and the witness are protected. Therapy is seen as potentially detrimen-

tal to child witnesses because of the potential for their recollections to be altered by repetition or suggestion. The very fact that a child 
needs psychiatric help may be used to discredit the child as a witness in the eyes of the jury.
If a child witness clearly requires psychological or psychiatric 
treatment and cannot wait for many months until the trial is over for the treatment to begin, mental health professionals should discuss the child’s needs with a representative of the legal service. The therapy may be allowed to proceed with some restrictions about what can be discussed . The therapist should be prepared 
to be called to court themselves in order to give evidence about the nature of their work. The court will want to be satisﬁ  ed that the 
child has not been coached by the therapist or told about infor-mation given by other witnesses .
Children’s testimony is worth hearing
The status of child witnesses has improved considerably in the last

The status of child witnesses has improved considerably in the last 
20 years. Modern psychological research shows that although most children under 3 years of age lack the cognitive capacities to be competent witnesses, many older children are able to produce use-ful evidential information provided they are questioned compe-tently. T o make full use of what children can remember, they need to be allowed to talk in a comfortable setting, guided by profession-als who are sensitive to developmental issues and aware of legal constraints. Child witnesses have often been traumatized by their experience. It is important that further distress caused by appear-ing in court is kept to a minimum and that children who need therapeutic help to deal with their trauma are not denied access to this in the pre-trial period.
www.childrenslegalcentre.com
www.victimsupport.org.ukhttp://www.homeofﬁ  ce.gov.uk/justice/what-happens-at-court/being-a-

witness
http://www.homeofﬁ  ce.gov.uk/documents/achieving-best-evidence/
guidance-witnesses.pdf
 1. Fundudis, T. (1997). Y oung children’s memory: how good is it? 
How much do we know about it? Child Psychology and Psychiatry 
Review ,2, 150–8.
 2. T err, L.C. (1986). The child psychiatrist and the child witness: traveling 
companions by necessity, if not by design. Journal of the American 
Academy of Child Psychiatry ,25, 462–72.
 3. Ceci, S.J. and Bruck, M. (1993). Suggestibility of the child witness: a 
historical review and synthesis. Psychological Bulletin ,113, 403–39.
 4. Flin, R. and Spencer, J.R. (1995). Annotation: children as witnesses—
legal and psychological perspectives. Journal of Child Psychology and 
Psychiatry ,36, 171–89.
 5. Saywitz, K. and Camparo, L. (1998). Interviewing child witnesses: a

 5. Saywitz, K. and Camparo, L. (1998). Interviewing child witnesses: a 
developmental perspective. Child Abuse and Neglect ,22, 825–43.
 6. Williams, G.A. (1998). Video technology and children’s evidence: 
international perspectives and recent research. Medicine and Law ,
17, 263–81.
 7. Hamilton C. (2005). Working with young people: legal responsibility and 
liability , pp. 102–6. The Children’s Legal Centre, Colchester.Table 9.4.2  Children giving evidence are often concerned about(7)
◆ People shouting at them in court
◆ Not understanding the questions
◆ Not being believed
◆ Giving ‘wrong’ answers
◆ Speaking in front of strangers
◆ Crying while giving evidence
◆ Needing to go to the toilet
(Reproduced from Hamilton, C. Working with young people: legal responsibility and liabil-
ity, pp. 102–6, copyright 2005, The Children’s Legal Centre.)

Table 9.4.3  A child appearing as a witness in court should 
know that(7)
◆ They have not done anything wrong
◆ They should always tell the truth
◆ They can take time to answer a question
◆ They should speak to the judge as clearly as possible
◆ Its OK to answer a question by saying ‘I don’t know’ or ‘I don’t remember’
◆ Its OK to answer a question by saying ‘I don’t understand’
◆ They must not guess or make up an answer
ity, pp. 102–6, copyright 2005, The Children’s Legal Centre.)9.4 the child as witness

9.5
Treatment methods for 
Contents
 9.5.1 Counselling and psychotherapy for children
 9.5.2 Psychodynamic child pscyhotherapy 
 9.5.3 Cognitive behaviour therapies 
for children and families
 9.5.4 Caregiver-mediated interventions for children and families 
 9.5.5 Medication for children and adolescents: current issues 
 9.5.6 Residential care for social reasons
 9.5.7 Organization of services for children and adolescents with mental health problems
 9.5.8 The management of child and adolescent psychiatric emergencies
 9.5.9 The child psychiatrist as consultant to schools and colleges
9.5.1 Counselling and 
psychotherapy for children
There is a remarkable lack of high quality research to support

There is a remarkable lack of high quality research to support 
an evidence base for counselling and psychotherapy for children. And the words ‘psychotherapy’ and ‘counselling’ are so non-speciﬁ  c 
that they should always be clariﬁ  ed in more detail. Nevertheless, 
these approaches are used frequently in child mental health. While most psychotherapeutic approaches are based on work with adults it is important to note that there are marked differences between children and adults. In spite of these obvious differences, psycho-therapy for children is usually based on techniques used for adults. However, psychotherapy that may work perfectly well for adults 
has to be modiﬁ  ed to accord with the developmental level of each 
child.
We each have a mental image of ‘a child’ . Often this is a stereotypical

child.
We each have a mental image of ‘a child’ . Often this is a stereotypical 
child aged about 5 to 10 years old. But the word ‘childhood’ covers the whole period from birth to adulthood, and of course every adult is also somebody’s child. In this chapter the term ‘child’ will be 
used to refer to anyone who is not an adult , but who has matured 
sufﬁ ciently to develop a clear concept of themselves as individuals 
and of the nature of the real world around them. The ability to dis-tinguish fact from fantasy is an important prerequisite for psycho-therapy. This develops as a gradual process with an important stage at around 2.5 years of age when children normally start to refer to themselves as ‘I’ for the ﬁ  rst time. Another stage occurs around 7 to

8 years of age when children develop a clear understanding of time and of the real world. If the therapist ignores these developmental issues it is likely that treatment will be harmful rather than helpful.
Psychotherapy is a very general term that implies treatment of 
mental dysfunction by psychological rather than physical methods. The aim is to improve function by changing cognition and emotions through the therapeutic relationship, by means of language, play, art, or drama. Dynamic child psychotherapy can be deﬁ  ned as 
a highly specialized technique where the primary aim is to explore a child’s conscious and unconscious thoughts, feelings, and con-ﬂ icts in such a way that inner resources become strengthened and 
enabled. It is child-led so that the child is able to follow and explore his or her own agenda, thus helping the child to make sense of the world and to ﬁ  nd his or her own solutions to problems and dilem-

mas. Therapy is mediated by language, which can either be verbal or non-verbal and may use play or creative activities such as drawing, painting, and modelling. Counselling children is very similar, but the therapist usually takes a more passive role than in psychotherapy 
and would not be so concerned with the interpretation of

1765
 unconscious processes. Cognitive behaviour therapy on the other 
hand is a highly structured approach focused on challenging false cognitions in order to change behaviour and emotions. It is an approach that can be rather easily adapted to children and made sufﬁ ciently enjoyable to engage their interest and cooperation.
Differences from adult psychotherapy
A number of interesting paradoxes and dilemmas  occur when 
treating children with psychotherapy (Table 9.5.1.1). For example, who should give consent for treatment. Should it be the child, a parent, both parents, or all three? Clearly, this depends on the age and understanding of the child, and each case should be approached in a way that puts the child’s needs ﬁ  rst. It is generally best to obtain

consent from the child and both parents. Any other arrangement is likely to lead to problems at some stage. Psychotherapy and coun-selling are traditionally non-directive and patient-led, but children, unlike most adults, need to be given some direction otherwise they become easily lost and confused. They cannot be expected to ﬁ nd their own solutions without guidance and support. Most 
psychotherapeutic approaches for adults are based on coming to terms with and ﬁ  nding explanations for problems that are rooted 
in the past. However, children are still busy making their past, and 
their main focus of concern and interest is the present and the immediate future. A further dilemma in child psychotherapy concerns the management of the transference relationship between therapist and patient, which is a reﬂ  ection of the parent–child

relationship. A high degree of trust has to be established to use transference effectively. At the same time, it could be argued that it is not really appropriate for young children to develop high levels of trust and dependence on a therapist whom they only meet brieﬂ  y 
in very artiﬁ  cial circumstances. Thus any interpretation of the 
transference relationship in child psychotherapy must be done carefully and with a good understanding of the subtle complexities of a child’s dependency on the parent.
Adult psychotherapy is usually based on a single theoretical 
model that explains mental mechanisms. Children, however, bene-ﬁ t from the freedom to experiment with a number of different 
models of their inner world and to learn how to use these ideas in a ﬂ exible and constructive way. The use of a single-theory therapy 
in child psychotherapy is best avoided.
Counselling and psychotherapy

There are undoubtedly differences between child psychotherapy and counselling, but they are difﬁ  cult to deﬁ  ne precisely. This may be because there is a continuum of therapeutic interventions, from 
advice and guidance at one end of a therapeutic spectrum through more specific counselling and psychotherapeutic techniques 
to intensive child psychoanalysis at the other end. Counselling 
children requires a high level of skill, but less theory and technique than in psychotherapy, and it is focused primarily on normal reactions to abnormal events.
Psychotherapy is directed more at psychopathology than normal 
reactions to stress. It is there fore essential to know about the normal

reactions to stress. It is there fore essential to know about the normal 
range of children’s responses to life events. For example, a 5-year-old child whose mother has just died will grieve differently from a 10-year-old child, because at 5 years of age most children have not yet developed a clear concept of death. Grief in a 5-year-old is most strongly inﬂ  uenced by the way the adults around the child 
react to the death, whereas a grieving 10-year-old child, although responsive to guidance from the adults around, will also have his or her own unique way of coping with grief. As a general rule, the younger the child the more important it is to consider the attitude and mental state of the parents.
Other psychotherapies
Dynamic psychotherapy based on the theories of Sigmund Freud and his daughter Anna Freud,
(1) Melanie Klein,(2) and others has

(1) Melanie Klein,(2) and others has 
been the mainstay of individual child therapy. More recently, Virginia Axline
(3) adapted the ideas that Carl Rogers(4) applied to 
counselling (trust, genuineness and understanding) and developed ‘play therapy’ as a speciﬁ  c technique for children. Subsequently, 
brief psychotherapy and interpersonal therapy have grown out of the need to update psychodynamic methods. Various forms of cog-nitive therapy are now increasingly used for children, although they were originally developed for the treatment of adults by Beck.
(5)
These therapies focus on a problem-solving approach to resolve current issues, rather than on resolving unconscious conﬂ  icts based 
in the past.
Natural emotional healing

(5)
Counselling and psychotherapy have been used with increasing frequency to help children cope with traumatic events such as death, divorce, abuse, illness, and so on. It is arguable whether this trend is at all helpful. Fortunately, the human psyche is remarkably resilient and there are powerful healing processes that take time, which in most cases achieve a satisfactory result. There are similari-ties between the way the body and mind respond to trauma and a strong correspondence between the natural healing processes that accompany both physical and emotional trauma. The initial healing process starts with a brief period where no pain or distress is felt whatever the cause of the trauma, and this is often accompa-nied by disbelief that such a thing could have happened. This ﬁ  rst

phase of shock and ‘denial’ is then replaced by the full impact of what has happened and is accompanied by high levels of physical 
or emotional pain. During the second phase the pain may be so 
severe that it interferes with everyday life, but this stage is usually over within 2 weeks. In the third stage, the healing process contin-ues for a period of up to 6 weeks when the emotional or physical wound is normally healed sufﬁ  ciently for the traumatized person 
to be able to return to everyday life, albeit with continuing pain and discomfort at times. The ﬁ  nal phase of the healing process then 
continues over the next 6 to 12 months, leaving a scar that will always remain.Table 9.5.1.1  Differences between children and adults in relation to 
therapy
Consent for treatment usually given by parent/carer rather than child

therapy
Child may nor understand or want therapyChildren need more help with problem solving than adultsTherapy should be relatively more directive and instructiveProblems tend to be rooted in present or recent pastTherapy should be mostly enjoyable for child to beneﬁ  t
Transference is complicated because children live with and need parents/carers
Different approaches needed at various stages of developmentChildren are developing and changing quickly so therapy needs to do this too9.5.1 counselling and psychotherapy for children

SECTION 9  child and adolescent psychiatry 1766
Routine counselling following traumatic events carries the risk 
of interfering with this normal healing process. Psychotherapy could also be misused to check that all is well, rather like opening up a wound unnecessarily, which will only serve to delay the healing process and might even introduce a secondary ‘infection’ . The parallel between physical and emotional healing provides some guidelines as to when and how counselling and psychotherapy should be used, as well as the dangers that can occur when they are misused.
The use of play in therapy
The fact that children are still developing language and commu-
nication skills  means that play is often useful as a method of 
communicating in a therapeutic way with children. Play is essential for normal development. It helps children to develop a repertoire of responses and encourages behavioural ﬂ  exibility. The main

communicating in a therapeutic way with children. Play is essential for normal development. It helps children to develop a repertoire of responses and encourages behavioural ﬂ  exibility. The main 
developmental stages of play need to be appreciated if it is to be used in an effective way in either counselling or psychotherapy (see Table 9.5.1.2).
Children will play with almost anything, and so the choice of 
play materials for use in psychotherapy requires careful thought. It is best to select toys that encourage imagination and creativity. It is important to remember that the type of play equipment provided will actually constrain the way the child plays. For example, there is 
a limit to what cars or toy animals can do. Similarly, a set of family 
dolls may have their usefulness restricted if there are not enough of them to represent all the key ﬁ  gures in the child’s life. A thoughtful

dolls may have their usefulness restricted if there are not enough of them to represent all the key ﬁ  gures in the child’s life. A thoughtful 
and appropriate choice of toys and play materials including draw-ing, modelling, and painting equipment can make the difference between the success and failure to engage a child in therapy.
Children’s play can be a pointer to what is going on in the child’s 
mind (either conscious or unconscious), but it can also mislead. A child’s play will only give a very general indication of what the child thinks and feels and will not provide precise information. Perhaps the best way of viewing the use of play in therapy is that it is an aid to communication—and no more than that.
The treatment setting
There are a number of steps that can be taken to make the treat-ment setting more beneﬁ  cial for the child and help to create a

There are a number of steps that can be taken to make the treat-ment setting more beneﬁ  cial for the child and help to create a 
relaxed atmosphere. How the therapy and the therapist are intro-duced to the child is of some importance. The attitude of the thera-pist is undoubtedly more important than the way the therapy room is organized and the more anxious and tentative the introduction, the more uneasy the child will be. There are no hard and fast rules 
about the duration or frequency of the treatment session. It is best to arrange it to suit the child. Some children ﬁ  nd more than 20 min 
with an adult extremely difﬁ  cult to cope with whatever their age. 
Many children ﬁ  nd the formal structure of therapy quite stressful

Many children ﬁ  nd the formal structure of therapy quite stressful 
and it may help to put the child at ease by talking about unimpor-tant issues before the session itself begins. Anxiety can also be reduced by organizing the sessions to be as predictable as possible in place and time. Making it clear to children that the therapeutic time is specially for them and that they are the focus of all their therapist’s attention can also motivate children to be more co-operative and to be less wary.

Each child’s experiences of distress must always be considered in the context of the child’s family circumstances, the child’s stage of development, and his or her temperamental characteristics. It follows that the therapeutic approach needs to be individually tailored and adjusted for each child. Nevertheless, it is possible to arrive at some general guidelines that will assist in treatment. The concern, interest, and supportive attitude of the therapist is central to the treatment process, since it is the interaction between the child’s need and the adult’s response that establishes the transfer-ence relationship.
The start of the ﬁ  rst session is particularly important because it 
sets the tone for the future treatment. The child should know the role that the therapist has and what the aims of the treatment are. Something needs to be said about the limits to behaviour in the session and the nature and degree of conﬁ  dentiality. It is important

to remember that complete conﬁ  dentiality cannot be assured. For 
example, the therapist may be presented with information that concerns the health or safety of the child as in the case of abuse, where information has to be disclosed for the beneﬁ  t of the child.
The timing and number of sessions needs to be agreed at this 
stage. Therefore it is often a good idea to suggest a limited number of sessions in the ﬁ  rst instance, together with an agreement to 
review whether or not further sessions are required. This type of introduction helps children to feel their needs are being taken seriously, especially if they are actively involved in the process. Sessions should start and ﬁ  nish on time and the links between the 
present and any previous sessions should be clariﬁ  ed.
Most children will remember their treatment experience for

Most children will remember their treatment experience for 
many years to come—if not for the rest of their lives. The child who feels uncomfortable, embarrassed, and misunderstood is likely to retain a memory that is painful and unhelpful. On the other hand, if the therapeutic experience was positive, where the therapist was seen as supportive, encouraging, and understanding, the memory is likely to be one that the child returns to again and again for emotional strength and support.
Different approaches to psychotherapy

There is a wide variety of jargon associated with various types of psychotherapy. Each approach has its own ‘language’ and associated special techniques. However, there is no evidence that any one method is better than another, and it would appear that the personal preference of the professional involved is more important in determining which approach is used rather than the characteristics Table 9.5.1.2  The development of children’s play
Age Type of play
12–18 months Symbolic play (e.g. block of wood is a car)
18 months–3 years Imaginary play (e.g. blocks become a family)3–7 years Imaginary friends in 30 per cent of children5–7 years Rule-governed make-believe games7 years onwards Imagination founded much more strongly on the 
 real world

1767
of the child. Whichever approach is used it is likely that there will 
be the same common themes in the focus of treatment. Common themes include dealing with feelings of anxiety and insecurity, difﬁ  culties in relationships, low self-esteem, and a feel-
ing of failure. These emotions are often generated by difﬁ  culties 
with aggression, jealousy, sexuality, and death.
A focus on the past versus the present
The child comes to psychotherapy with a range of problems rooted in the past. A decision has to be made whether to focus the therapy on trying to understand and come to terms with the past, or to consider how a child might best cope with what is actually happen-ing in the here and now. The danger  in concentrating primarily on

the past is that it may interfere with the child’s ability to cope with the present and plan for the future. While it is important to learn from what has happened in the past, children tend to learn more from what is happening in the present in their daily lives. Understanding how their emotional stress was generated in the ﬁ rst place may not lead to a resolution or to a greater ability to deal 
with current problems. It is generally helpful to start therapy with an acknowledgement of what has happened in the past and a consideration of how that might affect what is happening in the present. In a few cases it may be helpful to focus more on the past, but only if the child has clearly become preoccupied with a particular issue from the past and is unable to move on. Normal development moves on so rapidly during childhood that any ﬁ  xation with the 
past can have serious consequences, thus every effort needs to be made to promote and sustain developmental progress.

Theory vs. common humanity
While it is undoubtedly helpful to have a theoretical framework within which treatment can take place, the observation that differ-ent psychotherapeutic approaches for the same type of problem can be equally effective suggests that the precise theoretical frame-work underpinning treatment may not be that important. The basic human qualities of kindness, trust, caring and understanding are perhaps the most important qualities in psychotherapy. It is not an unusual experience for therapists to ﬁ  nd that their early cases 
turn out to be the most successful, which is probably due to the enthusiasm and therapeutic optimism of the new therapist. It is clearly important to hold on to these therapeutic qualities as one becomes more experienced.
Supportive counselling vs. in-depth psychoanalysis

It is easy to assume that the more intensive the psychotherapy and the more it explores the deep unconscious world, the more effec-tive it must be. Clearly there is no reason why this should be the case. For example, one would not expect a surgeon to cut deeper for greater effect or a physician to prescribe more medication than is necessary. This would only increase the adverse effects of the treatment. It is not difﬁ  cult to see that regular psychoanalysis two

or three times per week could be quite disruptive to family life merely as a result of the time commitment alone. There are also other potential problems for children who are treated with inten-sive psychoanalysis over a period of years, as this may delay or shape a child’s development in an unhelpful way. On the other hand, it might be equally inappropriate to commence supportive counselling for a child who is deeply disturbed and whose need for loving care and protection is not being met. These primary and 
basic needs must always be given priority.
Cognitive therapy vs. psychoanalytically based 
There has been an increased interest in cognitive therapy and cog-

nitive behaviour therapy, where the emphasis is much more on the here and now and the behavioural consequences of abnormal thought patterns. The techniques used in cognitive therapy for anx-iety and depressive disorder are described in Chapters 6.3.2.1 and 6.3.2.3 respectively. The only modiﬁ  cation that is required for their 
use in children is to adapt them to the developmental stage and the level of cognitive ability that the child has reached. Cognitive thera-py has a theoretical advantage for use in children in that its focus is more on the present and the future, in contrast to most psychoana-lytically based psychotherapy. Its approach is strongly based on learning new ways of coping. Cognitive therapy is pragmatic and active rather than passive and reﬂ  ective, making it generally more

appropriate for the needs of younger children. Unfortunately, there 
is as yet limited evidence to support the  theoretical underpinning 
of the various cognitive models of childhood disorders.
Limit setting vs. free expression
It is a common dilemma to know how much freedom children should be allowed to express themselves. Some children appear to enjoy pushing the limits to see how far they can go. Other children appear too inhibited and need encouragement to express them-selves. Part of the art of child therapy is to strike a comfortable balance between control and freedom. Children gain nothing from disruptive and destructive behaviour, even if they normally tend to be quiet and inhibited. Indeed, they rapidly develop overwhelm-ing feelings of anxiety and insecurity if they do not feel sufﬁ  ciently

contained. It is essential that the therapist retains a very clear notion of what behaviour is acceptable and what is not. It is there-fore the therapist’s responsibility to set the scene and establish the boundaries of acceptable behaviour within the therapeutic context. Should the child go beyond the limit then a warning should be 
given, and if the child persists it is quite acceptable to end the ses-
sion early or at least until the disruptive behaviour has stopped. The therapist’s reaction to bad behaviour should make it quite clear that it is unacceptable. However, the emotional response should be neutral or sad, in much the same way that one might behave in a shoe shop when a desirable new shoe does not ﬁ  t as expected.
Closeness vs. distance
It is natural for an adult to be physically much closer to younger

It is natural for an adult to be physically much closer to younger 
children and then to become more distant as they grow older. For example, it is quite natural for an adult to hold the hand of a 3- or 4-year old and to physically guide the child. On the other hand, any physical contact with a teenager can easily be misconstrued and is likely to be most unwelcome. In addition to the developmental perspective, every child has its own preferred degree of closeness or distance from other people. The task of the therapist is to judge what is right for each occasion. It is absolutely essential that the therapist must always avoid intruding into the child’s space in any way that could be construed as abusive. This may prove difﬁ  cult 
where children are unsure of their boundaries and seek out physical contact (in cases of sexual abuse, children may seek out 9.5.1 counselling and psychoterapy for children

SECTION 9  child and adolescent psychiatry 1768
sexual contact). However, to maintain an artiﬁ  cial physical or emo-
tional distance can be perceived as disinterest or even rejection by some children. T o achieve a comfortable level of emotional warmth and physical closeness in therapy is obviously a very important matter, but a relaxed approach in the therapeutic relationship is generally best.
Individual vs. group therapy
There are no agreed guidelines to determine which child would beneﬁ  t from an individual or from a group approach to psycho-
therapy. Some children, however, ﬁ  nd the emotional intensity of

therapy. Some children, however, ﬁ  nd the emotional intensity of 
undivided adult attention too much to cope with and learn better from others in a group situation. As the selection of cases for group psychotherapy tends to be determined by the therapist’s skills, there is no clear evidence that one approach is better than any other. Nevertheless, there is a growing literature on group therapy for children and an increasing interest in this method of treatment if only because the cost per case is likely to be less.
Practical issues in child psychotherapy
Involving parents and the school

The younger the child, the more helpful it is to involve the parents in treatment. How this is managed will depend to some extent on the resources available. It is generally best for separate therapists to work with the child and with the parents. However, there will usually be occasions when it is helpful for the child’s therapist to have some direct contact with the parents as a way of monitoring progress and keeping a link between the therapy sessions and the child’s real world. As children grow older they tend to become increasingly inhibited by the involvement of their parents, so it is helpful to check with the young person how they would like the contact with their parents to be organized. All children should be considered in the context of the family and the school because so many risk factors are associated with these environments. Parental support for the treatment is a critical factor in a successful out-

come. Equally, it is possible for parents to undermine treatment by 
their negative comments or overintrusiveness after each session.
The extent to which a child’s school should be involved needs to 
be carefully considered on an individual basis. Although it is best to have the full co-operation of the school, this may not be possible.
Conﬁ  dentiality and record-keeping
Conﬁ  dentiality in relation to the individual therapy sessions is clear-
ly important, but it should not dominate. The most vital issue is that the children feel safe in what they say and do during the session. They need to know that there is a reasonable level of conﬁ  dentiality. 
However, there are obvious exceptions to the general rule of conﬁ  -

dentiality: for example, in cases of child abuse or criminal activity, or in cases where the child may be at risk from harming itself. A suit-able compromise is to indicate to the child that their session would be treated as conﬁ  dential, but there may be occasions when it is best 
to inform their parents or somebody else about important informa-tion that was given during the session. This would only occur after discussion between the therapist and the child—the overarching rule is that it must be in the best interest of the child.
There is obviously a need for accurate record-keeping for each 
session, partly to keep track of the therapeutic process and also for medico-legal purposes. It is unnecessary to include the more detailed recording of the therapeutic process in the ofﬁ  cial notes if

the record is purely for training purposes. These training notes then remain the property of the therapist and must be kept at the same level of security as the ofﬁ  cial notes.
Failure to attend
If there is a genuine and legitimate reason why a child is unable

to attend for a therapy session then little or no importance needs be attached to this. On the other hand, if therapy sessions are cancelled repeatedly, cancelled with inadequate excuses, or simply not attended it is essential for the therapist to question whether therapy is actually achieving the original stated goal. Factors such as family disadvantage, parental stress, and the severity of the child’s problems all increase the likelihood of failing to complete therapy successfully. It is all too easy to either blame the carers or to ration-alize failure to attend as being some problem in the child, rather than an issue that could be due to the therapist. Of course, one good reason for failure to attend is that the child no longer needs to. It is usually unhelpful to send out repeated appointments that are not attended. A reasonable compromise is for one reappoint-ment to be made, then if this is failed for a letter to be sent to

the carers or to an older teenager asking them to contact you if 
further sessions are thought necessary. Occasionally, if treatment is at a very critical stage or if there is high level of concern about the child, it would then be appropriate for more effort to be put into arranging a further appointment.
Individual and cultural issues
A child’s sociocultural background needs to be taken into account when planning therapy. T emperament, age, gender, and intellectual ability are also important factors to be considered. Ethnicity, on the other hand, is probably not that signiﬁ  cant an issue. Some children 
enjoy, and beneﬁ  t from, the freedom to express themselves openly 
and with little constraint; others need direction and structure if they are to resolve psychological problems. There is no point in try-ing to ﬁ  t the child to the therapy rather than the other way round.

One factor that supersedes all cultural and individual factors is that children generally wish to enjoy themselves and to have a good time. They are pleasure-seeking beings who, unlike most adults, see no beneﬁ  t from the experience of pain and distress of therapy.
Bringing therapy to a satisfactory conclusion is more likely to 
happen if the treatment was well set up in the ﬁ  rst place and if 
achievable goals were agreed. Because it is so easy for therapy to lose its focus, it is helpful to consider how and when the treatment will be concluded at the same time as setting it up. Even if treat-ment goals have not been achieved it should still be possible to end the therapy on a positive note, identifying areas where self-knowledge has been increased and anything that has been positive in the therapeutic relationship.

The objectives of training in psychotherapy are primarily to do with increasing knowledge and understanding of the issues that arise during psychotherapeutic treatment, many of which have been referred to above. It is essential for this to be underpinned by a sound knowledge of child development, but less important for

1769
therapy to be founded in any particular psychodynamic theory. 
The key training method in psychotherapy is the conduct of thera-py under supervision. Choosing a supervisor and the role of that supervisor are critically important issues for the trainee therapist, since the relationship between supervisor and trainee mirrors that of the therapist and client even if there is a clear understanding that the purpose of the supervision is not intended to be therapeutic. Most therapists ﬁ  nd that supervision continues to be helpful even 
after they are ‘trained’ .
Measures of effectiveness and outcome
There is a lack of high quality research to support an evidence base for counselling and psychotherapy for children. One of the main difﬁ  cul-

ties in conducting research is in the selection of an adequate control group. Reviews of psychotherapeutic treatments indicate a general improvement in children that persists for many months after the inter-vention. However, it seems likely that the theoretical basis for the  psychotherapeutic approach is less important than the caring and sup-portive relationship that develops between the child and the therapist.
Fitzgerald, M. (1998). Child psychoanalytic psychotherapy. Advances in 
Psychiatric Treatment ,4, 18–24.
Jacobs, W.J. (2002). Individual and group therapy. In Child and Adolescent 
Psychiatry (4th edn) (ed M. Rutter, E. Taylor), pp. 983–97. Blackwell 
Rutter, M., Bishop, D. Pine, D., et al. (eds.)(2008). Rutters’s Child and

Rutter, M., Bishop, D. Pine, D., et al. (eds.)(2008). Rutters’s Child and 
Adolescent Psychiatry  (5th edn.). Blackwell, Oxford.
Roth, A.D. and Fonagy, P . (2005). What works for whom? A critical review 
of psychotherapy research. Guilford Press. New Y ork.
Useful web sites
www.youngminds.org.uk
www.psychnet-uk.com
www.babcp.com
www.rcpsych.ac.uk
1. Freud, A. (1974). Introduction to psychoanalysis . Hogarth Press, London.
2. Klein, M. (1932). The psychotherapy of children . Hogarth Press, London.
3. Axline, V . (1969). Play therapy . Ballentine Books, New Y ork.
4. Rogers, C. (1951). Client centred therapy in current practice: implications 
and theory . Houghton Mifﬂ  in, New Y ork.
5. Beck, A.T. (1976). Cognitive therapy and emotional disorders .
International Universities Press. New Y ork.
9.5.2 Psychodynamic 
child psychotherapy

Psychodynamic psychotherapy for children is based on a range of 
assumptions concerning mental functioning that have gradually evolved over the past 100 years out of the theories of Sigmund 
Freud. As these assumptions have been widely reviewed, we need to provide only a very brief introduction here.
Psychodynamic child clinicians assume that:
(a) The child’s presenting difﬁ  culties may usefully be seen in terms 
of thoughts, feelings, wishes, beliefs, and conﬂ  icts. This entails 
the assumption that mental disorders can meaningfully be understood as speciﬁ  c organizations of a child’s conscious or 
unconscious mental states.
(b) To under stand conscious experiences, we need to consider

(b) To under stand conscious experiences, we need to consider 
non-conscious narrative-like experiences, analogous to  conscious fantasies, which powerfully affect behaviour, affect regulation, and the capacity to handle the social environment. Modern neuroscience, with fMRI studies that show cortical response reﬂ  ecting processing to meaning in the absence of 
awareness and non-conscious motivation,
(1) has put the exist-
ence of an unconscious beyond debate.
(c) Intense relationship experiences are represented in the mind as

(c) Intense relationship experiences are represented in the mind as 
structures of interpersonal interaction, and are aggregated across time before coming to form a schematic mental struc-ture, which is often represented metaphorically as a neural network. Within many models, self-other relationship repre-sentations are also considered the organizers of emotion, as feeling states are seen as coming to characterize particular pat-terns of self-other and interpersonal relating (e.g. sadness and disappointment at the anticipated loss of a person).
(2)
(d) Inevitably, wishes, affects and ideas will at times be in conﬂ  ict 
with one another. The psychodynamic therapeutic approach sees such conﬂ  icts as key causes of distress and the lack of a 
sense of safety. Adverse environments either increase the inten-sity of conﬂ  ict or fail to equip the child with the capacity to

sense of safety. Adverse environments either increase the inten-sity of conﬂ  ict or fail to equip the child with the capacity to 
resolve such incompatibilities through mental work.
(3) They 
may also set the child on a developmental trajectory in which the normal development of key psychological capacities is undermined, thereby reducing the child’s competence to resolve mental conﬂ  ict.
(4) For this reason, while reviewers of 
psychodynamic psychotherapy often contrast conﬂ  ict and 
development-focussed approaches, the reality of developmen-tal trajectories means that the conﬂ  ict and deﬁ  cit often come 
together.
(5)
(e) The child’s mental mechanisms for dealing with intrapsychic 
conflict include defence mechanisms that distort mental representations in order to reduce conﬂ  ict and unpleasure.
(6)
Such self-serving distortions of mental states relative to an 
external or internal reality are frequently demonstrated exper-imentally and have become accepted.

(6)
(7–10)  Classiﬁ  cation of 
defences has frequently been attempted,(11,12)  often as a meth-
od for categorizing individuals or mental disorders,(13,14) but
few of these approaches have stood the test of time or achieved general acceptance.
(f) Behaviour may be understood in terms of ‘complex meanings’ , 
that is, mental states that are not explicit in action or within the awareness of the person concerned. Thus, symptoms of disorders are classically considered as condensations of conﬂ  icting wishes together with the failed defence against 
conscious awareness of those wishes. Therapy is an effort to seek personal  meaning,
(15) and to elaborate and clarify implicit 
meaning structures—a process that may turn out to be 9.5.2 psychodynamic child psychotherapy

SECTION 9  child and adolescent psychiatry 1770
the essence of psychodynamic psychotherapy—rather than to 
give the patient insight in terms of any particular meaning structure.
(g) A relationship with a supportive and respectful empathic adult 
will beneﬁ  t the young person, not least by enhancing their 
own understanding and emotional responsiveness. The nature of the relationship with psychodynamic therapists varies across therapies—from the highly transferential and fantasy oriented
(17)
to the quite practical and supportive,(18) although most thera-
pies contain elements of both.(19) Establishing an attachment 
relationship with a clinician (i.e. with an interested, under-standing, and respectful adult) may be a new experience for some young people
(20) and is believed to trigger a basic set of 
human capacities for relatedness that appears therapeutic, apparently almost regardless of content.
(21–27) The child’s

(21–27) The child’s 
relationship with the therapist often appears to become the vehicle for disowned aspects of the child’s thoughts and feel-ings, creating a process termed transference, which enables the psychoanalytic clinician to understand the child’s representa-tion of relationships and his or her feelings about them.
(28)
The roots of child psychoanalysis lie in Freud’s observation of young children, most notably of the young Anna Freud’s wishful dream for strawberries,
(29) his grandson’s separation game,(30) and his case 
study of Little Hans, a 5-year old with a phobic disorder who was treated by his physician father under Freud’s supervision.
(31)
Play therapy, incorporating both an insight-oriented interpretive 
approach and the developmental assistance perspective, was intro-duced by Hermine Hug-Helmuth.

(31)
(32) Thereafter, two women, in 
strong opposition but frequently making reference to each other, established the ﬁ  eld: Anna Freud
(33) and Melanie Klein.(34)
Klein’s approach was to regard children’s play as essentially the 
same as free association with adults; that is, motivated by uncon-scious fantasy and activated by the relationship with the therapist (transference). The child’s anxiety required verbalization (interpre-tation) if it was to be addressed. The focal point of therapy was the verbalization of anxieties concerning destructive and sadistic impulses, whilst the child’s external relationships (with parents, teachers, etc.) were seen as peripheral and irrelevant.
A key construct was the notion of projective identiﬁ  cation.
(35)
This term referred originally to the infantile tendency to project

(35)
This term referred originally to the infantile tendency to project 
unwanted aspects of the self on to another person. The clinician, by understanding the child’s perception of her as a person, could gain valuable insights about conﬂ  ictual aspects of the child’s experience 
of himself. Bion
(36) described how the ‘container’s’ capacity to 
understand and accept the projections could be critical both to successful therapy and to normal development. More recently, Kleinian child analysts have been less likely to offer early interpre-tations of deeply unconscious material; defences beyond projective identiﬁ  cation are more commonly considered.
(17, 37)
Strongly inﬂ  uenced by Melanie Klein, Donald Winnicott ﬁ  rmly 
endorsed her emphasis on the impact of the ﬁ  rst years of life on 
childhood psychopathology.(3) However, he also introduced new

childhood psychopathology.(3) However, he also introduced new 
techniques (e.g. drawing) and various theoretical innovations, including the identiﬁ  cation of a transitional space between self and 
other where the subjective object and the truly objective object could simultaneously be recognized.
(38) The notion of transitional space, an intermediate area between the intrapsychic and the inter-
personal, was critical to the development of an interpersonal(39,40)
and intersubjectivist(41) approach within psychoanalysis.
Along this continuum, Anna Freud was perhaps most concerned 
with the child’s developmental struggle with a social as well as an 
internal environment. Her background as a teacher may have led her to be as concerned with children’s actual external circumstances as with their unconscious worlds.
(42) Her focus was restricted to

(42) Her focus was restricted to 
complications and conflicts arising from the child’s libidinal impulses and, unlike Melanie Klein, she rarely focussed on innate aggression. The interpretation of defence was central to her technique.
(43) Her approach paid careful attention to limitations 
on the child’s cognitive capacities (ego functioning) and had as its explicit aim the restoration of the child to a normal developmental path.
(44) Her concern with normal development led her to evolve 
a model of pathology as a disturbance of normal developmental processes, and she developed a sy stematic analysis of  such anomalies 
using the concept of developmental lines.
(45) Her propositions are 
in many respects consistent with modern developmental psycho-pathology.
(46) Developmental help is aimed at facilitating the

(46) Developmental help is aimed at facilitating the 
forward movement of the psychological processes that underpin social cognition and interpersonal function, and which include mentalization, impulse control and emotion regulation, symbol-ization and the use of metaphor, and the capacity for play.
(47,48) 
Notwithstanding the curious historical fact that Anna Freudian, Kleinian, and Winnicottian approaches all originated in London, the Anna Freudian approach came to dominate child therapy in the United States,
(49) whereas in the United Kingdom and in Latin 
America Melanie Klein’s approach proved more popular.(50)
Two comprehensive and detailed histories of the ﬁ  eld have been 
provided.(51,52)

T echniques of child therapy differ considerably depending on the degree of pathology manifested by the child. Two sets of technique may be distinguished: those with single diagnosis, usually involving anxiety, are offered what most would recognize as ‘classical’ forms of psychodynamic, insight-oriented therapy. Those with multiple diagnoses, severe behavioural problems and/or emergent personality disorders
(53) require a different psychodynamic treatment 
approach. These will be discussed separately.
Principal features of ‘classical’ technique

Child psychotherapy involves the elaboration of distorted and, to a lesser or greater extent, non-conscious mental representations. The therapist, using the child’s verbalizations, non-verbal play, and other behaviours, aims to provide a rational understanding of the child’s non-conscious thoughts, feelings, and expectations. This understanding may encompass and integrate earlier modes of the child’s thinking into a more mature, age-appropriate framework.
(54)

(54)
With young children, the treatment involves the use of toys, play, and any device that helps to engage the children in a process of self-exploration. The therapist works to elaborate the children’s understanding of their emotional responses, their unconscious concerns about their body, and the way their symptoms might link together anxieties about relationships, including non-conscious aggressive or sexual thoughts and other conﬂ  ictual feelings in rela-
tion to the parents, siblings, and peers.

1771
The techniques used by the child therapist go beyond interpre-
tive interventions and were usefully enumerated by Paulina Kernberg.
(55) She delineated: (i) supportive interventions , which are 
aimed at addressing the child’s anxiety and increasing the child’s 
sense of competence and mastery through the provision of infor-mation, reassurance, empathy, and suggestions (ii) facilitative state-
ments , which seek chieﬂ  y to maintain the therapeutic relationship 
with the child by reviewing, summarizing or paraphrasing the child’s communications and (iii) clariﬁ  cations , which review and 
summarize the child’s communication, and which usually involve relabelling communication or behaviour. Clariﬁ  cations also serve 
to focus the child’s attention on certain patterns in his behaviour indicative of unconscious determination.
Interpretation may centre on: (i) the content of the child’s

Interpretation may centre on: (i) the content of the child’s 
communications (ii) the contents that the child systematically omits from verbalization (iii) the child’s non-verbal behaviour (iv) the nature of the child’s play, including the roles that he or she tends to assign to himself and to the therapist (v) the child’s current emotional state, particularly sadness, anxiety, or guilt, and; (vi) dreams that the child recounts in his sessions. While the therapist may be able to link the child’s therapeutic material to past experiences with attachment ﬁ  gures, such reconstructive inter-
pretations are rare in child therapy. It is only gradually that the therapist hopes to be able to generate an emotionally meaningful understanding of the impact of past experiences on current anxiety and conﬂ  ict.
Paulina Kernberg
(55) distinguished between three types of child

(55) distinguished between three types of child 
therapeutic interpretation. First and most common are interpreta-tions of defences, which aim to show the child how it protects itself from thoughts, feelings, and actions that it considers unacceptable. For example, the therapist may draw the child’s attention to repeat-ed examples of self-denigration, and hint at his anxiety about being thought boastful; this serves a dual function in both bringing to the child’s awareness what he is protecting himself from and also in prompting him to find alternative strategies to cope with warded off ideas. Second are interpretations that address the child’s unconscious wishes, which are themselves thought to underpin behaviour. Frequently, these interpretations are made following interpretations of defences. Finally, child therapists might address the child’s past experiences. The therapy may reveal traumatic 
experiences, and some therapists consider it helpful to bring these

experiences, and some therapists consider it helpful to bring these 
memories into consciousness. It should be noted that current psychodynamic theory in no way assumes that addressing such trauma directly is essential to cure. Far more important in terms of therapeutic progress is addressing the distorted relationship repre-sentations that are sequelae to early trauma.
(56)
Whatever the interpretation, the child therapist aims to address 
the child’s anxiety and how other emotions relate to it. Thus, destructive wishes would most likely be taken up in connection with the child’s anxiety about his or her angry feelings. Child thera-peutic technique also demands that the child’s attempt actively to struggle with these wishes be clearly acknowledged. Interpretations are ideally tied to a highly speciﬁ  c context, such as the child’s expe-
rience of anxiety associated with his anger that an ungenerous but otherwise valued therapist will not give him a special treat for his birthday.

An important part of child therapeutic work involves the child’s 
parents. Some of this work is psychoeducational; in particular, parents often need guidance on appropriate, uncritical, warm, and playful methods of child rearing. Discussion of the child’s symp-
toms may enable parents to gain greater awareness of the child’s difﬁ culties and how their own representation of the child may be 
distorted.
(57)
Psychodynamic technique with complex 
childhood disturbances
The child psychotherapeutic approach has been extended to apply not 
only to so-called neurotic disorders, but also to the under standing 
and treatment of borderline, narcissistic, delinquent, and conduct disordered youngsters, as well as schizoid and even psychotic chil-dren.
(53) The classical psychoanalytic approach as outlined above

(53) The classical psychoanalytic approach as outlined above 
has clear limitations with these children: anxiety may not be acces-sible; there may be little evidence of conﬂ  ict/of the child’s struggle 
with wishes; defences may be hard to identify, and the child may be developmentally inaccessible to insight. Taking these issues into consideration, we have suggested that a dramatic modiﬁ  cation of child psychotherapeutic technique may be in 
order
(19) based on what Anna Freud called ‘developmental help’ . 
We have described this intervention in detail,(58) and colleagues 
in the Netherlands have elaborated and researched this form of therapy.
(59)
Essentially, the therapist begins by performing mental functions 
of which the child is incapable, or by showing the child ways of performing these functions until he or she can take over and do it himself. These interventions are used with pathologies traditionally deﬁ ned as ego defects, deﬁ  ciencies in relationships, or develop-

mental disturbances—pathologies understood here as mental process disturbances. These techniques have sometimes been labelled remedial education or ego-support, but, broadly, the therapist’s aim is to free the mental processes from inhibition and to aid in the development of these processes. The therapist achieves this by: (i) providing a safe place and relationship within which the child can dare to change or wish to be different (ii) making up for some deﬁ  cits in the parenting that the child has received by 
providing him with the missing elements (iii) stimulating delayed 
or stunted developmental processes by drawing the child’s atten-
tion to what is missing, and encouraging his interest and desire to function better and (iv) using interpretations not to uncover the source of his difﬁ  culties but to help the child understand the extent 
and impact of his problems, his contribution to his developmental difﬁ culties, and to confront the role played by his environment.

and impact of his problems, his contribution to his developmental difﬁ culties, and to confront the role played by his environment. 
The main foci of these modiﬁ  ed forms of child therapeutic inter-
vention are six-fold:
(a) The enhancing of reﬂ  ective processes ; that is, the understanding of 
how mental states (beliefs, desires, wishes, and emotions) deter-mine human behaviour. This is achieved by encouraging the observation and labelling of both physical and psychological experiences in the immediate situation. It is assumed that, regardless of cause, the ﬁ  nal common pathway of most personal-
ity disorders is a dramatic impairment of reﬂ  ective function.
(60)
(b) The enhancing of impulse control  by identifying and helping the

(60)
(b) The enhancing of impulse control  by identifying and helping the 
child to exercise ways in which impulses may be channelled into socially acceptable forms of behaviour. The therapist may initially have to control this herself by ‘setting limits’ . She tells the child what he may and may not do during the sessions, explaining that she will not let him hurt her or himself, or damage things in the room.9.5.2 psychodynamic child psychotherapy

SECTION 9  child and adolescent psychiatry 1772
(c) Affect regulation  is an important aim of developmental work. 
It can be assisted by the verbalization and labelling of affect, and by explaining to the child possible reasons for his feelings; for example, that his aggressive attacks are reactions to his sense of being threatened and endangered.
(d) The elaboration of strategies involv ing symbolization and 
metaphor for enhancing cognitive self-regulation . The therapist 
demonstrates her own capacities for reflection and the moderation of experience through mental representation rather than physical action or coercion.
(e) Focussing the child’s awareness on the mental states of others .
This is achieved initially by focussing interventions around the child’s perception of the therapist’s mental states, which can be a precursor to reﬂ  ective processes in relation to the self.
(f) Developing the child’s capacity for play , initially with physical

(f) Developing the child’s capacity for play , initially with physical 
objects, then with another person and, ultimately, with ideas. 
Play is not simply the creation of a pretend world but has the 
aim of creating a safe opportunity for alternative meanings of the child’s experiences to emerge. This can show the child how his habitual ways of thinking and feeling represent but one of multiple ways of construing reality. Perhaps more importantly in this context, he can experience adults relating to him, as perhaps they have not often related to him before.
While the child therapist working with such severely disturbed 
children is still ‘working in the transference’ , in the sense that the child’s feelings about the therapist remain central, this is no longer thought to entail the displacement of feelings and ideas from one person to another, e.g. from the parent to the therapist. Rather, the clariﬁ  cation of the child’s feelings about the therapist may be

the most effective route towards assisting the child to acquire a reﬂ ective capacity. In this way, the therapist conveys that the child’s 
affect can be understood and managed by another person.
Indications, contraindications, and the 
selection of procedures
There is general agreement on the indications for child psychother-
apy.(61) These have traditionally included: (i) high IQ and verbal 
ability (ii) supportive environment (iii) conﬂ  ict-related pathology 
(iv) adequate internal and external object relations and (v) the presence of anxiety. Contraindications include: (i) pervasive devel-opmental disorder (ii) psychosis (iii) major deﬁ  ciencies in psycho-
logical capacities and (iv) family constellations incompatible with adherence to treatment, for example, chaotic home environments or psychologically severely disturbed parents.
As described above, however, by substantially modifying

As described above, however, by substantially modifying 
traditional technique, child therapists have successfully worked with populations beyond this restricted group,
(62) treating children 
with a variety of psychological deﬁ  ciencies.
One way of conceptualizing the difference between the needs of 
the two groups is by using the classical distinction between mental representations and mental processes in cognitive science.
(63)
Classical techniques primarily impact on the organization and shape of the child’s mental representations of self-other relation-ships.
(64) By contrast, developmental help for the more severely 
disordered group aims at developing the function of mental pro-cesses, which may have been defensively distorted in early develop-ment,
(65) by strengthening and supporting the patient’s adaptive defences and helping them to label and verbalize their thoughts 
and feelings.
The distinction between classical technique and developmental

The distinction between classical technique and developmental 
help is a heuristic one. In reality, all child therapeutic treatments involve both, but it is nevertheless suggested that developmental help is essential for the effective treatment of severe disturbances, whilst it remains an ‘optional extra’ for children with neurotic disturbances.

At the beginning of psychodynamic child therapy, the therapist’s aim is to communicate that: (i) sessions have the purpose of expressing thoughts and feelings through play and words and (ii) the therapist is trying to help the child make sense of his experi-ence so that he can master his inner turmoil in a more effective manner. Children are generally able to develop a therapeutic alliance in the context of an empathic, respectful, non-exploitative relation-ship with an adult. A similar collaboration is established with the parents, and early meetings also allow the child therapist to acquire relevant information and assess family interactional patterns that may be relevant to the child’s treatment. In early sessions, the ther-apist attempts to interest the child in meaning and to link mental states to activity by using child’s play to address the child’s under-standing of momentary anxieties, and to explain that his struggles,

thoughts, and feelings may be explored through his verbalizations 
and behaviour.
(66) Children who are able to use therapy tend 
to respond to these interventions with an enhancement of the therapeutic alliance, showing greater freedom in their play and verbalizations. It is important to note that the same process of relationship building characterizes other individual therapies such as cognitive behaviour therapy (CBT).
(23)
The middle phase of child therapy is expected to focus on the sys-tematic use of transference interpretations and the initiation of the ‘working through’ process. The development of the transference is facilitated by a therapeutic structure that emphasizes regularity, consistency, and the specialness of the hour of therapy.
(67) The 
child’s play is ‘interpreted’ , but normally these interpretations are kept within the context of the play situation. Clinical experience 
suggests that interpreting the play in reference to the child’s ‘real’

suggests that interpreting the play in reference to the child’s ‘real’ 
feeling only serves to disrupt the child’s communication.
(68)
The major themes in children’s lives are often expressed in the 
therapeutic relationship. Internal working models of attachment 
relationships, for example, will come to colour the child’s relation-
ship with the therapist,(69) be that a pattern of reluctance in forming 
trusting relationships (avoidant/dismissing) or excessive anxieties about separation and sometimes angry preoccupation with the therapist’s thoughts and feelings (resistant/preoccupied). This, of course, opens up the possibility of correcting distortions and mastering conﬂ  icts and associated anxieties. The child gains infor-
mation (insight) in a relational context that elaborates his under-standing of his experience, provides him with a way of coping with thoughts and feelings that make him feel uncomfortable and interrupts maladaptive interactions.

(70) Progress is often slow, and 
regression and progression tend to alternate as children struggle to face these anxieties without undue repression. Y et, gradually, given a capacity for the symbolic transformation of experience, they are able to bring their experience of internal and external

1773
worlds into play and can therefore internalize the therapeutic atti-
tude to solving their problems. Of course, development is helpful too in this regard.
(71)
The ending of treatment
Indications for the termination of long-term child psychotherapy are both external and internal to the therapy. External indications are not restricted to symptomatic improvement, but include consider-ations of changes in family interaction and peer relationships. Relational changes indicate a capacity to use caretakers, teachers, and others as sources of protection, guidance, comfort, and models of identiﬁ  cation. In general, the therapist seeks evidence that the child 
has returned to the path of normal development, can cope effectively with stress and conﬂ  ict, and can respond with greater freedom to 
adaptive demands coming both from within and without.
There are also indications from the child that the therapy may be 
ended. Some were enumerated by Paulina Kernberg
(72) as follows:

(72) as follows: 
(i) the therapist ﬁ  nds more opportunities for interpretation than 
for confrontation (ii) the child manifests more reﬂ  ectiveness and 
the capacity to make interpretations (iii) there is greater freedom, expressiveness, and pleasure in play (iv) there is insight and humour and (v) the child assumes responsibility for his own actions.
The end of psychodynamic therapy often generates anxiety

The end of psychodynamic therapy often generates anxiety 
and can bring a temporary reactivation of symptoms and the re-emergence of dysfunctional patterns of interaction within the family. As the therapy creates an attachment relationship, its termi-nation may be an essential part of resolving attachment-related concerns (e.g. fear of abandonment, rejection). Mourning the anticipated loss of the therapy and the therapist may well be an essential part of a successful ending to treatment. Other issues may 
involve children’s disappointments—with themselves, with the 
unfulﬁ  lled promise of the therapy, and with adults who do not 
measure up to their expectations. Research and clinical experience suggests, however, that as this turmoil subsides, progress continues to be made after the end of treatment.
(57, 73, 74)
Efﬁ cacy
The most comprehensive survey of outcome studies speciﬁ  cally 
concerned with psychodynamic treatment was undertaken by Kennedy

Efﬁ cacy
(75) as part of a project sponsored by the British Association 
of Child Psychotherapists—although there are other comprehen-sive reviews of treatment of children
(76–80)  and of psychosocial 
interventions limited to ‘evidence-based treatments’ .(81, 82) The gen-
eral reviews highlight that research of psychodynamic treatment in the ﬁ  eld of child therapy has lagged behind the evaluation of other 
approaches.
There are relatively few randomized controlled trials of psychody-
namic psychotherapy.
(83–88) All but one of these trials contrasted 
individual child psychotherapy with another (evidence-based) treat-ment. In addition, several studies employed quasi-randomized meth-ods of assignment, such as postcode
(89) or therapist vacancy.(90, 91)  Six 
studies reported on ﬁ  ndings with matched comparison groups.(92–96)

A further two studies reported non-matched control groups.(97, 98)
Two further studies used an untreated but poorly matched control 
sample.(99, 100)  In addition, there are a number of open trials of child 
psychotherapy employing no comparison groups.(101–107) Three 
studies used an experimental, single-case methodology.(108–110)
Considering studies of the common disorders of childhood 
separately, Muratori and colleagues(91) contrasted the efﬁ  cacy of 11 weeks of psychodynamic therapy to treatment as usual in 
58 children with depression and anxiety. At 2-year follow-up, 34 per cent of the treated group were in the clinical range on symp-tomatic measures, compared to 65 per cent of the controls. Treatment effects increased during the 2-year follow-up period (the so-called ‘sleeper effect’), including a move int o the non-clini cal

range for the average child with internalizing problems (in the psychodynamically treated group only).
(90) It is encouraging that 
psychodynamic psychotherapy patients sought mental health services at a signiﬁ  cantly lower rate than those in the treatment as 
usual comparison condition over the 2-year follow-up period.
In a multi-centred European trial,
(88) moderate childhood 
depression was shown to be accessible to a brief individual psy-chodynamic psychotherapy. At 7-month follow-up, none of the moderately to severely depressed young people met criteria, which is comparable to children treated with a combination of ﬂ  uoxetine 
and CBT.
(111) The presence of anxiety/dysthymia signalled particu-
lar suitability for individual treatment, whilst comorbidity with oppositional deﬁ  ant disorder (ODD) or conduct disorder (CD)

and CBT.
lar suitability for individual treatment, whilst comorbidity with oppositional deﬁ  ant disorder (ODD) or conduct disorder (CD) 
contraindicated it. These children, however, appeared to do better with family based approaches that were also psychodynamic in ori-entation. A classic study, and for many years one of the only studies that considered the issue of intensity of psychological therapy, focussed on speciﬁ  c learning difﬁ  culties as a target of therapy.
(93,112)
Boys in middle childhood with serious reading problems beneﬁ  ted 
signiﬁ  cantly from psychodynamic psychotherapy. There was a 
dose-response relationship over the 2-year treatment period. Children who received more intensive help (more sessions per week) beneﬁ  ted most from the therapy in terms of self-esteem, the

dose-response relationship over the 2-year treatment period. Children who received more intensive help (more sessions per week) beneﬁ  ted most from the therapy in terms of self-esteem, the 
capacity to form relationships, and the capacity to work, including frustration tolerance. Particularly interesting is the multi-centred randomized trial of the treatment of sexually abused girls treated in individual psychotherapy and psychoeducational group therapy.
(87)
Trowell et al .(87) randomized 71 sexually abused girls to either

(87)
Trowell et al .(87) randomized 71 sexually abused girls to either 
30 sessions of individual psychoanalytic psychotherapy or 18 ses-sions of group psychotherapy with psychoeducational components. These young people presented with a range of psychiatric prob-lems, most commonly post-traumatic stress disorder (PTSD) and depression. Psychodynamic treatment was somewhat superior to psychoeducation, but the difference was not as marked as might be expected. Superiority was particularly evident in relation to PTSD and generalized anxiety disorder (GAD). Depression, how-ever, was relatively less likely to improve, as was separation anxiety. A subsequent report underscored the importance of the mother’s support for the therapy as a predictor of improvement in the children and the beneﬁ  t that the mothers gained in terms of their 
own mental health from the child’s treatment.
(113)
A chart review of the outcome of 763 cases in child psychotherapy

(113)
A chart review of the outcome of 763 cases in child psychotherapy 
has been carried out at the Anna Freud Centre in London.(103)
While this retrospective methodology has severe limitations, the study reached a number of fairly robust conclusions, that need to be explored further in controlled, prospective investigations. The main ﬁ  ndings were:
(a) Attrition was low compared to reports of other treatment 
(b) Children with pervasive developmental disorders (e.g. autism) 
or intellectual disability did not do well, even with prolonged, intensive treatment. Children with serious disruptive disorders also had relatively poor outcomes.9.5.2 psychodynamic child psychotherapy

SECTION 9  child and adolescent psychiatry 1774
(c) Y ounger children improved signiﬁ  cantly during psychody-
namic treatment, and gained additional beneﬁ  t from 4–5 weekly 
sessions.
(d) Anxiety disorders, particularly speciﬁ  c rather than pervasive 
symptoms, were associated with a good prognosis, even if the primary diagnosis was of a different type, e.g. disruptive disorder.
(e) Children with emotional disorders and/or severe or pervasive 
symptomatology responded very well to intensive treatment (4–5 sessions per week), but did not show satisfactory rates of improvement in non-intensive psychotherapy.
(f) Predictors of improvement varied considerably between sub-
groups of the full sample, and, by subdividing the sample according to diagnostic group and developmental level, it was possible to predict a majority of the variance in outcome within the subgroups.
Limitations of the psychotherapeutic 
approach
The empirical status of all psychodynamic approaches remains

approach
The empirical status of all psychodynamic approaches remains 
controversial. The body of rigorous research supporting psychody-namic therapies for adults for most disorders remains limited, particularly relative to research supporting pharmaceutical treat-ments and even other psychosocial approaches such as CBT.
(80)
There are both practical and theoretical difﬁ  culties to mounting 
trials of dynamic therapies, and these go some way to explaining the lack of evidence (e.g. identifying suitable control groups for long-term intensive treatments, difﬁ  culties in operationalizing the 
treatment methods, the expense of mounting trials sufﬁ  ciently 
powered to yield information on what treatments are appropriate for which disorder, the failure to tightly manualize psychodynamic treatments, etc.). Those who argue for continued investment in this approach (correctly in our view) point to the limitations of the evi-dence base supporting CBT

(114) or pharmacological approaches.(115)
Ultimately, however, such a negative case cannot persuade policy makers and funders, and, without intense research on the effective-ness of the method deeply rooted in and shaped by psychological models of pathology, the long-term survival of this orientation is not assured.
(116) This is not to say that the techniques that have

(116) This is not to say that the techniques that have 
evolved as part of this approach will not survive (they are effective, and clinicians, being pragmatic people, will continue to discover and use them), but they will be increasingly absorbed into alterna-tive models, and the unique approach pioneered by Freud and out-lined in this chapter might not continue. Child therapists thus face formidable challenges to their clinical and theoretical convictions, to their professional status, and, as evidence-based medicine and managed care relentlessly expand their control over reimbursement and deny payment for child therapy, to their livelihood. If child psychotherapy is to have a future, its unique effectiveness for speciﬁ  c childhood disorders must be demonstrated in randomized 
controlled trials. We believe that children with severe disorders

controlled trials. We believe that children with severe disorders 
of personality and multiple psychiatric diagnoses are indeed well suited to and dramatically benefit from a psychotherapeutic approach. Such faith, however, now requires support from empiri-cal investigations.Further information
Fonagy, P ., Target, M., and Gergely, G. (2004). Psychoanalytic perspectives 
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9.5.3 Cognitive behaviour

1341–5.
9.5.3 Cognitive behaviour 
therapies for children and families
Cognitive behaviour therapy (CBT) is derived from both behav-
ioural and cognitive theories. Using concepts such as operant con-ditioning and reinforcement, behavioural theories treat behaviour as explicable without recourse to description of mental activity. In contrast, mental activity is central to all concepts derived from cognitive psychology. Both sets of theories have been of value in explaining psychological disorders and, in the design of interven-tions they have proved an effective combination.
Central to that part of cognitive theory that is relevant to 
CBT is the concept of ‘schemas’ , ﬁ  rst described in detail by Jean 
Piaget.
(1) A schema is a mental ‘structure for screening, coding, and

Piaget.
(1) A schema is a mental ‘structure for screening, coding, and 
evaluating impinging stimuli’ .(2) The origin of mental schemas lies 
in the pre-verbal phase when material is encoded in non-verbal images that, as the child’s language develops, gradually become ver-bally labelled. They form part of a dynamic system interacting with an individual child’s physiology, emotional functioning, and behav-iour with their operation depending on the social context in which the child is living. There are similarities but also differences between schemas and related concepts in psychoanalysis, such as Freudian 
‘complexes’ and Kleinian ‘positions’ .
Schemas can be seen as organized around anything in the child’s

Schemas can be seen as organized around anything in the child’s 
world, especially objects, beliefs, or emotions. They develop from past experience. The processing of new information in relation to such schemas can usefully be seen as involving the evaluation of discrepancies between information that is received and informa-
tion that is expected. If there is a discrepancy, (the information not corresponding with that expected), then during the coding process information may be distorted so that it no longer creates discom-fort, or, more adaptively, it may be incorporated into a modiﬁ  ed 
schema.
Cognitive development

schema.
The theory of cognitive development that Piaget constructed on the basis of an immense amount of experimental work was charac-terized by stages of development. He described characteristic fea-tures of the sensori-motor (0–2 years), pre-operational (2–7 years), concrete operational (7–12 years), and formal operational (12 years onwards) stages. Before the end of a stage is reached the child is incapable of showing more advanced thinking. In particular, the child’s thinking before the concrete operational stage is character-ized by egocentricity and an inability to take the perspective of another person. Abstract reasoning is not possible for the child until the formal operational stage is reached.
Even though Piaget’s views of the limitations of the cognitive

Even though Piaget’s views of the limitations of the cognitive 
abilities of young children have been strongly criticized especially on the grounds that he was judging egocentricity on the basis of ﬁ ndings obtained in highly artiﬁ  cial situations, Piaget remained a 
dominant influence in cognitive psychology and education throughout the twentieth century. It is now widely accepted that, 
although obviously young children are less competent than those in middle childhood and these are less competent than adolescents, cognitive competence advances much more rapidly than Piaget described and the social context in which a child’s competence is investigated has a much more profound inﬂ  uence on performance

than he allowed. Children do a great deal better in naturalistic circumstances than when they take part in experiments. Further, coaching can improve performance to a level not previously obtainable. For example, it has been shown that, with preliminary training, 3-year-old children understand that drawings of thought bubbles can represent what people think. They can distinguish between thoughts and actions, recognize that thoughts are subjec-tive and that two people can have different thoughts about the same events.
(3)
Investigation of the development of the ‘theory of mind’ held by

(3)
Investigation of the development of the ‘theory of mind’ held by 
children has revealed that between 3 and 4 years they begin to real-ize that other children can be deceived by appearances and hold false beliefs they themselves do not hold. This shows that, given the right circumstances, children of this young age are able to ‘de-centre’ and are not necessarily limited by egocentricity. By the age of 8 years children have such stable concepts of their own self-esteem that they are capable of reliably completing self-esteem question-naires about their own feelings and performance in comparison to other children.
(4) Some schemas in young children are however

(4) Some schemas in young children are however 
relatively unstable, gradually increasing in stability as they get older. For example, it has been shown that attributional style (the ten-dency to attribute adverse events either to the self or to external circumstances) does not become stable until early adolescence, 9.5.3 cognitive behaviour therapies for children and families

SECTION 9  child and adolescent psychiatry 1778
though it may be identiﬁ  ed earlier if the events are particularly 
salient to the child in question.(5)
It has been hypothesized(6) that maladaptive schemas developed 
during childhood are responsible for the formation and 
maintenance of adult psychopathology. Building on this model, a therapeutic approach (schema-focused therapy) based on the iden-tiﬁ cation of particular maladaptive schemas has been proposed 
for adults. Subsequently Stallard and Rayner
(7) have developed a 
schema questionnaire that builds on adult work to identify such maladaptive schema in 11 to 16-year-old school children.
Technique and management in the 
paediatric age group
Although there are certain common principles, CBT does not

Although there are certain common principles, CBT does not 
involve, as will be seen, a single approach that can be applied across all disorders; it is better seen as a family of approaches with certain core elements in common. In adults the type of disorder and the individual circumstances of the patient will determine the choice of therapeutic methods. In children and adolescents the cognitive level of the patient will also need to be taken into account. Though the age of the child will give some indication of the cognitive level of the child, there is wide variation in competence amongst chil-dren of the same age. Further, the therapist may use the skills of an educationist to bring the child’s competence up to a level at which the child can more actively participate in therapy. Kendall
(8) sug-
gests indeed that one of the therapeutic roles that the therapist should adopt is that of educator , who needs communication skills

(8) sug-
gests indeed that one of the therapeutic roles that the therapist should adopt is that of educator , who needs communication skills 
to assist children to learn to think for themselves.
Behaviour therapy or CBT?
In principle, the decision as to whether to include a cognitive com-ponent in therapy depends on whether the clinical formulation incorporates cognitive distortions or biases. In practice, because of their cognitive limitations CBT is rarely used in children under the age of 7 years. Treatment in children younger than 7 years is predominantly behavioural, with the cognitive component limited to coping self-talk. Conditioning approaches to the treatment of feeding and sleeping problems as well as enuresis and encopresis usually have a very small or no signiﬁ  cant cognitive component.
In some conditions such as anxiety disorders, especially speciﬁ  c

In some conditions such as anxiety disorders, especially speciﬁ  c 
phobias, where desensitization and reinforcement approaches are widely used in adults, the use of a mainly behavioural approach does not reduce effectiveness. A cognitive component may never-theless be incorporated because the CBT principles of collabora-
tion, openness, and guided discovery, usually less marked when 
purely behavioural approaches are applied, are advantageous to the patient.
Aids to cognitive tasks
Where experience with adults suggests that cognitive tasks add signiﬁ  cantly to the effectiveness of treatment, as in depressive 
disorders and problems of social relationships, even young people in early adolescence will usually be able to co-operate as well as adults. The cognitive treatment of younger children with these conditions may be helped by the use of age-adapted techniques.
(9)For example, card-sorting games  have been devised to help children

(9)For example, card-sorting games  have been devised to help children 
distinguish between thoughts, feelings, and situations. Puppets  can 
be used to facilitate discussion as part of the assessment process, to model alternative ways the child might cope with difﬁ  cult situa-
tions and to engage the child in rehearsal and practice of new skills. Story telling  can provide an insight into the child’s inner world; 
they provide a way of externalizing and accessing the child’s cogni-tions, allow an opportunity to challenge the child’s assumptions, introduce the child to more positive ways of coping, and can be used to model success and help the child gain more functional assumptions and beliefs.
Working with parents

Parents play many roles in the delivery of CBT to children and adolescents. T o begin with, even up to mid-adolescence, it is nearly always parents who identify the behaviour and emotional problems that lead to advice being sought. They are the people most likely to press for psychological help. It is they who have to persuade often reluctant children and adolescents to attend and participate in a service that their offspring may fear, not without reason, will result in stigmatization.
They are then likely to play a major part in the assessment 
process. From mid- to late adolescence, the patient or client will be the main source of information, but before that it is the parents and teachers who will often provide most relevant information. If treatment is proposed it is they who need to give consent, though 
their child will also need to assent if the therapy is to have any 
chance of succeeding.
Once treatment planning has begun, the part that parents play

Once treatment planning has begun, the part that parents play 
will depend very much on the age of the child or adolescent, the diagnosis, family circumstances (especially the quality of the rela-tionships between parents and child), and the degree to which the assessment has revealed that the parents as well as being the main carers are also involved in the origin and maintenance of the prob-lem. Most explanatory theories of anxiety disorders in children, for example, point to the ways in which parents can provide inappro-priately anxious models for imitation by their children. In a small scale study it has been shown that changing parental attributions can, in itself, result in improvements in problem behaviour scores on a questionnaire.
(10) Parents may also be seen as clients in their

(10) Parents may also be seen as clients in their 
own rights in parallel sessions, as co-therapists or as facilitators of therapy for their children. Therapists dealing with adolescent offspring are often in a difﬁ  cult position vis-à-vis  parents in that 
they will wish to encourage autonomy and independent decision-making in the child or adolescent, while needing the parents to monitor homework, encourage further attendance, and provide information on progress.
The involvement of parents also brings ethical dilemmas. There 
are three main areas of ethical concern.
(11) The therapist often 
has to balance the different viewpoints of parents and children, a particular problem in the management of oppositional and con-duct disorders where children often fail to acknowledge the existence of problems that are causing distress to their parents. There is fre-quently need to address family issues such as marital conﬂ  ict that

are clearly relevant yet not the reasons why the child has been brought for treatment. Finally, there is the need to achieve genuine collaboration with parents, making explicit their role as co-thera pists. 
This is made easier if children are also actively involved as fellow

1779
collaborators, taking responsibility for progress and being encour-
aged to make suggestions for alternative approaches. A collaborative stance may however not be possible if it becomes clear that there are child protection issues with one or both parents involved in maltreatment of their children. Wolpert and her colleagues provide a useful checklist for clinicians to help assess how far they are attempting to balance different viewpoints in issues involving dif-ferent family members and promoting collaboration.
Failure to engage and failure to respond
In adolescents, lack of motivation for change is often a major impediment to engagement in therapy. Not only is there often a failure to recognize the importance of a problem, to accept the need for change or to appear to understand why change is necessary, but there may also be an absence of the level of self-belief, self-conﬁ  dence, or self-efﬁ  cacy that is necessary before hopeful steps

can be taken in the right direction. In these circumstances tech-niques of motivational interviewing will help the therapist to achieve engagement.
(12)
The reasons for non-response to CBT in adults have been 
discussed by Kingdon et al.(13) Common problems include unsuit-
ability for treatment possibly arising from misdiagnosis, resistance to treatment, an inadequate number of sessions, difﬁ  culties in the 
therapeutic relationship and the presence of concurrent social and/or physical pathology. Non-response in children and adolescents arises from similar issues, with, additionally, complicating prob-lems arising from negative parental attitudes and behaviour.
Cognitive distortions and deﬁ  cits
A characteristic constellation of cognitive deﬁ  cits and distortions

A characteristic constellation of cognitive deﬁ  cits and distortions 
underlies the presence of anxiety disorders in children and adoles-cents. A central feature is the exaggerated perception of threat aris-ing from an inability to assess accurately the seriousness of danger. Thus a deﬁ  cit in perceptual competence results in cognitive distor-
tion. The characteristic nature of the threat involved will depend to a considerable degree both on the stage of cognitive development of the child and on the social demands that are encountered during that particular phase of life. Pre-school children are most likely to be threatened by separation from parents; children aged 5 to 12 years by feared situations at school and adolescents by social situations as well as wider concerns such as environmental pollu-tion. Certain fears and phobias such as fear of spiders and snakes appear more biologically based and are present through childhood

to adolescence.
These cognitive deﬁ  cits and distortions both result in and are 
maintained and increased by abnormal levels of physiological arousal and by behavioural avoidance of the feared situations. Autonomic arousal produces symptoms such as dry mouth, palpi-tations, and abdominal pain and these may be misinterpreted as 
implying serious threatening illness. Panic attacks may be catastro-
phized and taken to mean that death is imminent. Avoidance of 
feared situations such as separation from parents in younger 
children, refusal to go to school in older children or to social events 
such as parties in adolescence prevent cognitive testing of the reality of the supposed threat and reinforce the cognitive distortion.The fact that anxiety disorder is partly genetically determined

such as parties in adolescence prevent cognitive testing of the reality of the supposed threat and reinforce the cognitive distortion.The fact that anxiety disorder is partly genetically determined 
means that children suffering from this condition have an increased risk of having anxious parents. Such parents are likely to model anxious behaviour, especially in the way they show over-protection to their children. Anxious children are therefore likely to be exposed to social learning situations at home that will increase the risk of avoidance of feared situations. Gene-environment interactions ensure that many parents who cannot bear to be separated from their children or who are anxious every time they leave the house will transmit their fears to their children both directly and indirectly. In adolescence, anxious young people may selectively choose shy, inhibited friends who reinforce their sense of unrealistic threat.
Techniques of assessment and intervention

The assessment of children with anxiety disorders by a cognitive behaviour therapist focuses on the identiﬁ  cation of cognitive 
deﬁ cits and distortions and the manner in which they are currently 
being reinforced, especially by avoidant behaviour. Nevertheless it is important that before enquiry is made along these lines a full history is taken of the development of anxious symptoms, the pres-ence of other symptomatology, the situations that increase and reduce anxiety, the presence of anxiety in parents, sibs, and friends, and the measures that have already been taken, especially by parents, to improve the condition. Skilled assessment involves listening to the anxious preoccupations of both children and parents sympathetically and without any hint of criticism.
There are a number of systematic cognitive approaches to the

There are a number of systematic cognitive approaches to the 
reduction of anxiety in children of which the most widely used is the four-step coping or FEAR plan, in which F = Feeling frightened 
(awareness of anxiety symptoms such as somatic aches and pains), E = Expecting bad things to happen (awareness of negative self-
talk), A = Attitudes and actions that can help (problem-solving 
strategies), and R = Results and rewards (rewarding for success, 
dealing with failure).
(14) The ‘Cool Kids’ programme is generally 
similar but puts more emphasis on parent involvement.(15) When 
parents show signiﬁ  cant levels of anxiety themselves, effectiveness 
of treatment is enhanced if parental anxiety management is included as part of treatment.
(16) A self-help book for parents broadly based 
on the same principles provides a practical approach to the management of anxiety, using the so-called COPE programme.
(17)
Treatment begins with one or two psycho-educational sessions

Treatment begins with one or two psycho-educational sessions 
in which the child and parent(s), together or separately, are given information about the way anxiety develops and is maintained, the manner in which the body shows anxiety (somatic symptoms), and the effects of avoidant behaviour and exposure to feared situations. It is important that these sessions are interactional with the child being encouraged to talk spontaneously about, for example, how he or she experiences somatic symptoms. The next few sessions involve children engaging in an exercise to identify their own nega-tive thoughts, to test them against reality and to develop positive thinking in situations that have previously triggered anxiety. This will usually need to be done in imagination before it is tried out using ‘graded exposure’ in real situations. There are advantages in teaching relaxation techniques before the child embarks on expo-sure to feared situations. The use of imagery, such as the ‘stepladder’

approach to a hierarchy of feared situations may also be helpful. 
When the child makes progress, as is usually the case, rewards such as outings or other treats may be built in to the procedure.9.5.3 cognitive behaviour therapies for children and families

SECTION 9  child and adolescent psychiatry 1780
Therapists vary in the degree to which they involve parents 
in management. The therapy can be delivered in a family context, parents can be seen separately from children, parents may not be seen at all, or the therapy may only be delivered to parents. Some centres use a group approach, with one or two therapists providing a group experience for parents and anxious children who go through the stages of treatment together and beneﬁ  t from learning 
of each others’ experiences. Some programmes have now been developed for use via the Internet with minimal personal contact with the child and family. Some therapists combine CBT with the use of medication, generally not anxiolytic agents because of the risk of dependency, but tricyclics or selective serotonin reactive inhibitors.
Evaluation of effectiveness and efﬁ  cacy
A systematic review of the effectiveness of CBT for anxiety

A systematic review of the effectiveness of CBT for anxiety 
disorders in childhood and adolescence identiﬁ  ed 10 randomized 
controlled trials that met inclusion criteria.(18) The outcome meas-
ure used was the remission of anxiety disorder. The remission rate was higher in the CBT groups (56.5 per cent) than in the control groups (34.8 per cent). The pooled odds ratio was 3.3 (CI = 1.9–5 .6). 
The authors of this review conclude that CBT deﬁ  nitely provides 
beneﬁ  t to children and adolescents with anxiety disorder, but that 
there is a lack of information concerning the value of CBT in younger children and that there are virtually no satisfactory studies comparing effectiveness with alternative treatments.
There is contradictory evidence concerning the importance 
of involving parents in therapy. Some
(19,20) ﬁ nd little or no beneﬁ  t, 
while others(21,22)  ﬁ nd a trend towards beneﬁ  t. A pilot study has

while others(21,22)  ﬁ nd a trend towards beneﬁ  t. A pilot study has 
found beneﬁ  t from a programme that did not involve children 
directly but only involved parents seen in a group, who applied what they had learned in the group in managing the situations in which their children showed anxiety at home. Information on the use of therapy delivered via the Internet is limited, but those that exist suggest that Internet treatment is highly acceptable to fami-lies, creates minimal dropout and is effective when added to clinic treatment.
(23) Dropout from more conventional treatment is likely 
to be high in single-parent families, ethnic minority families, and where anxiety levels are not conspicuously high.
(24) There is evi-
dence that the presence of co-morbid disorders does not reduce the efﬁ cacy of CBT.
(25) The addition of antidepressants may increase

(25) The addition of antidepressants may increase 
the efﬁ  cacy of CBT, especially in the treatment of school refusal.(26)
Limited ﬁ  ndings from long-term studies suggest that treatment 
beneﬁ  ts from the delivery of CBT to anxious children are main-
tained over at least 6 years.(27)
There is also evidence from controlled studies for the effective-
ness of interventions, especially the FRIENDS programme(28) in 
the prevention of anxiety and depression in early adolescence. Stallard et al.
(29) have shown how this programme can be delivered 
successfully by school nurses.
These evaluative studies have provided most encouraging 
ﬁ ndings for the effectiveness of CBT in this condition. However the 
ﬁ ndings also make clear that CBT, while producing worthwhile and 
persistent beneﬁ  ts in most children and adolescents with anxiety

persistent beneﬁ  ts in most children and adolescents with anxiety 
disorders, is not effective in a signiﬁ  cant number of cases and 
in a signiﬁ  cant number of others it is only partially effective. It is 
also less effective in socially disadvantaged groups. Finally, most evaluative studies have been carried out in highly specialist centres and there is a lack of evidence for their value in everyday 
practice.
(18)
The classical signs of depressive disorders, such as chronic misery 
and unhappiness, lack of interest in food, and motor retardation, may be seen as early as the ﬁ  rst year of life. Infants and young chil-
dren who show such symptomatology may well suffer depressive experiences similar to those of older people though in the pre-verbal 
phase there is no reliable method available to conﬁ  rm this possibil-

ity. Awareness of feeling states develops towards the end of the second year of life.
(30) By 2 to 3 years children realize that there can 
be a variety of personal reasons for an emotional reaction. By 4 years there is some consensus about the kind of situations that will provoke the common emotional reactions, including fear, sadness, and anger.
(31) By 5 or 6 years a child is capable of under-
standing the concept of stability of mood, ‘always being unhappy or just now and again’ , and by 7 or 8 years concepts of shame and guilt are understood at least in simpliﬁ  ed form. Enduring and rela-

tively stable negative attributions about the self become possible at around this age and the concept of death as a permanent state is established. By 13 to 14 years, emotional experiences of adult inten-sity occur and mature cognitions about different mood states will have been attained. Although the above account relates stage of development to chronological age, there is wide variation in the ages at which cognitive competence is gained. Further, the settings 
in which children are questioned or encouraged to express them-
selves freely and spontaneously, for example in play situations will 
greatly inﬂ  uence their capacity to show their abilities.
The cognitive model underlying CBT approaches to children and 
adolescents does not differ from that with adults. It is assumed that thoughts are the primary experience of depression and that

adolescents does not differ from that with adults. It is assumed that thoughts are the primary experience of depression and that 
depressed mood is secondary. Dysfunctional assumptions, includ-ing low feelings of self-worth, self-blame for events in the past, and hopelessness about the future are present either as stable features of a depressive personality or as a reaction to adverse experiences, real or imagined. Depressed children and adolescents systematically distort their experience to match their beliefs about themselves. At some point, these negative thoughts are automatically experi-enced without reflection. Increasingly situations are avoided because of a fear of negative outcomes. Therapy involves identify-ing and reality testing these negative thoughts. In addition the patient is encouraged to enter into activities that will be rewarding and disconﬁ  rm pessimistic assumptions.

Initial assessment will involve taking a full history of the develop-
ment of symptoms and the factors that reduce or exacerbate them, the child’s functioning in different settings, and an account of family relationships. If the child is taken on for CBT, a typical approach
(32)
begins with the establishment of symptom status by the use of questionnaires such as the Children’s Depression Inventory
(33)
in young patients and the Mood and Feelings Questionnaire(34)
in adolescents. The goals of therapy are then discussed in a collab-orative manner with emphasis on what the child or young person wishes to achieve. The proposed therapeutic approach is then explained together with the importance of homework outside the

1781
therapy sessions. An indication of the number of sessions likely to 
be required, usually 12–16, is given. In early sessions an account of the child’s current daily activities is obtained. Adolescents are helped to keep a diary of their activities and moods. In a form of ‘affective education’ a check is made on the vocabulary the child uses to describe feelings and links are then established between the child’s mood and the activities he or she is undertaking.
During the next sessions, in collaboration with the child, 
homework is planned that aims to increase activity to the level pre-viously undertaken. Emphasis is placed on the resumption of everyday activities rather than offering treats or special occasions. At this point a problem-solving approach may be indicated. This 
begins with problem deﬁ  nition, followed by brain-storming a

begins with problem deﬁ  nition, followed by brain-storming a 
number of different solutions. The outcomes for different solutions are discussed and a plan developed to achieve what seems to be a satisfactory outcome. Homework involves attempts to implement the plan while keeping a record of progress and how this has inﬂ  u-
enced mood.
At least from early adolescence it will usually be possible to 
introduce self-monitoring procedures, in which the child identiﬁ  es

introduce self-monitoring procedures, in which the child identiﬁ  es 
and notes his level of mood in relation to the thoughts he is experi-encing. The child is encouraged to imagine different situations and to record how each situation makes him feel. The child is encour-aged to continue this process at home, recording what happens so that his experience can be discussed in the next session. This pro-cess is accompanied by self-evaluation training, a form of cognitive restructuring in which children learn to evaluate themselves in a more positive manner. They are encouraged to consider the evidence for having a poor opinion of themselves and then to examine carefully more positive alternative explanations. This pro-cess may be expected to reduce negative automatic thoughts.
A comprehensive evidence-based review of controlled evaluation

A comprehensive evidence-based review of controlled evaluation 
of cognitive behavioural psychotherapy for children and adoles-cents with depressive disorders
(35) identiﬁ  ed 12 studies that fulﬁ  lled 
methodological criteria. Most reported positive outcome for CBT post-treatment and at short-term follow-up. However, studies with longer follow-up periods from 9 months to 2 years found that a sizable percentage of subjects continued to report significant depressive symptoms or a recurrence of their depressive illness.
More recently the results of a major multi-centre trial, the 
Treatment of Adolescent Depression study (TADS) have been reported. In this study 479 adolescents, aged 12 to 17 years with depressive disorders were allocated randomly to a combination of ﬂ uoxetine and CBT, ﬂ  uoxetine alone, CBT alone and an inert pill

placebo. After 12 weeks of treatment the effects of combination therapy were clearly superior to either form of monotherapy and greatly superior to pill placebo. Fluoxetine alone was superior to CBT alone and to placebo, but CBT alone was not superior to 
placebo. On the other hand, ﬂ  uoxetine alone was accompanied 
by higher rates of suicidal events and this did not occur in the combined group. It seemed therefore that CBT protected against the suicidality linked to ﬂ  uoxetine use. The investigators concluded 
that the combination treatment produced the best outcomes.
(36)
The published evidence mainly relates to children and adoles-
cents with mild or moderate depressive disorders. There is some indication both from the TADS described and from other evidence that more severe depressive disorders do not respond as well or 
perhaps not at all to CBT alone.
(37)
Attempts to use CBT to prevent depression in adolescents have

(37)
Attempts to use CBT to prevent depression in adolescents have 
met with varied success. One universal school-based approach 
found no difference at 2 to 4-year follow-up in children who received a teacher-administered cognitive behavioural intervention compared with a control group.
(38) In contrast, positive effects 
were found for a CBT intervention targeting 13–18-year-old children of parents with depressive disorders.
(39) Application of 
the Resourceful Adolescent Programme has also been shown to produce promising results in preventing depression in younger adolescents.
(40)
Conduct disorder
Both young children with oppositional disorders and adolescents

(40)
Both young children with oppositional disorders and adolescents 
with more severe conduct disorders show characteristic cognitive distortion in their thinking. They recall inaccurately high rates of hostile cues in social situations and when neutral remarks and movements are made by their peers, they see these as hostile.
(41) In 
competitive situations with peers they exaggerate the aggressive behaviour of others and underestimate their own aggressiveness. These distorted attributions lead them into aggressive behaviour which then triggers angry behaviour from peers so that the origi-nally neutral environment does indeed become more hostile.
Aggressive children and adolescents also have difﬁ  culties in 
problem-solving, both in experimental and naturalistic situations. 
They prefer rapid action-orientated solutions to those that require 
reﬂ ective thinking before any action is taken. Underlying this

reﬂ ective thinking before any action is taken. Underlying this 
tendency to prefer rapid, aggressive solutions is the fact that their 
social goals relate more to the need for dominance and revenge 
than for afﬁ  liation.
(42)
Parents of aggressive children also show cognitive distortions 
that are of relevance to the way they discipline their children.(43)
This is of relevance both to the understanding and the manage-ment of childhood conduct disorders. For example, it has been shown that mothers of children with conduct disorder tend to attribute their children’s difﬁ  cult behaviour to deliberate wilfulness 
that is not within their children’s capacity to control. They perceive themselves as helpless in the face of their children’s behaviour. These cognitive distortions prevent them from acting effectively as parents, for example by drawing ﬁ  rm boundaries between accept-
able and unacceptable behaviour.

Until the early 1980s there were really no effective, evidence-based psychological interventions for children and adolescents with con-duct disorder. Since that time a number of moderately effective psychological measures have been developed. All of these, includ-ing the cognitive behavioural techniques described below are only likely to be successful if they are combined with psychosocial meas-ures directed towards the family as well as with appropriate educa-tion. All approaches require preliminary assessment of the child and family to identify the severity of the disorder and the possible presence of co-morbid disorders as well as to determine suitability for the approach envisaged.
Cognitive approaches to conduct disorder have been summa-
rized by Lochman et al .
(44)Problem-solving skills training (PSST)9.5.3 cognitive behaviour therapies for children and families

SECTION 9  child and adolescent psychiatry 1782
has been developed for children aged 7 to 13 years. The programme 
is delivered over 25 sessions.(45) The group leaders teach problem-
solving skills such as generating multiple solutions to a problem and reﬂ  ecting on the different consequences of the alternatives. 
The skills are applied to interpersonal situations with teachers, 
parents, peers, and siblings. Parent participation is a major compo-nent of the training, with parents observing the sessions and acting as co-therapists in supervising the use of the new skills in the home.
The Anger Coping and Coping Power Programme  is a school-based 
prevention programme delivered in group sessions to 13–14-year- old children.
(46) The group sessions focus on enhancing emotional 
awareness, anger management training, attribution retraining and perspective-taking, social problem-solving and social skills training, behavioural and personal goal-setting, and handling peer pressure.

Multi-system therapy  was designed as a multi-level intervention 
for 12 to 15-year-olds with multiple, severe antisocial problems.
(47)
Highly trained and closely supervised psychologists manage individualized programmes in the home setting. A variety of treat-ment approaches, including parent training, family therapy, school consultation, and individual therapy are employed in association with social measures such as helping lone mothers to ﬁ  nd employ-
ment are used. The aim is to achieve change in one area before targeting another.
Functional Family Therapy  combines family systems and 
cognitive behavioural approaches. The programme begins with an engagement and motivation phase in which the therapist addresses maladaptive beliefs in the family system thus aiming to increase expectations for change, reduce negativity and blaming, build respect for individual differences and develop a strong alliance between family members and the therapist. Practical behavioural

interventions are designed to produce change and this is followed 
by a generalization phase in which the family is encouraged to interact effectively with the various systems in the community with which it is in contact.
Parent Management Training Programmes  usually involve parents 
of young children with oppositional or conduct disorders. They derive from work originally carried out by Patterson and his colleagues at the Oregon Social Learning Center. His ﬁ  ndings 
established the importance of coercive parental behaviour in the development of childhood aggression. Many treatment pro-grammes have been based on their work,
(48,49)  which focus on ways

(48,49)  which focus on ways 
of reducing parental coerciveness, often in group settings. Parents are taught to pinpoint problem behaviours, to apply positive rein-forcement when their children’s behaviour is more appropriate and to learn problem-solving and negotiating techniques. It has been suggested that the incorporation of a cognitive component into parent training, using a ‘thoughts, feelings, behaviour cycle’ can improve effectiveness of this approach.
(50)
Evaluation of efﬁ  cacy and effectiveness
All of the above programmes have been evaluated in controlled 
clinical trials and have been shown to be moderately effective.(51–53)

(50)
However, virtually all the controlled studies have been carried out in highly resourced specialist centres. There is a conspicuous lack of studies of effectiveness carried out in routine clinical care.Attention deﬁ  cit hyperactivity 
disorder (ADHD)
Children with ADHD show a range of cognitive deﬁ  cits of atten-
tion and concentration with a strong predisposition to impulsivity, accompanied by explosive temperament and poor regulation of affect and impulses. Until recently these problems have been explained on the basis of deﬁ  cits in one of two cognitive pathways. 
It has been proposed that there is a deﬁ  cit in executive function, 
based on deﬁ  cient inhibitory control arising from frontodorsal 
striatal brain networks.

(54) Such failure of control results in deﬁ  cits 
in self-monitoring, planning, attentional control, and executive skills. Stimulant medication remedies these deﬁ  cits by increasing 
the activity of inhibitory pathways. Alternatively the condition has been attributed to disturbances in motivational processes, manifest as aversion to delay in gratiﬁ  cation. More recently Sonuga-Barke,
(55)
has proposed that both these mechanisms are supported by the 
evidence and that there are two distinct but complementary neuro-developmental bases for ADHD which is thus, at least in the pre-school period, psychologically heterogeneous. As children get older and executive function matures, deﬁ  cits in executive functions

may become more prominent in affected children, especially in the areas of inhibition, set shifting, working memory, planning, and ﬂ uency.
(56)
Information about children with suspected ADHD needs to be 
obtained from both parents and school teachers as the child is 
likely to behave differently in the two settings. Both interviews and rating scales should be used. Observation of the child can conﬁ  rm 
the presence of ADHD, but cannot rule it out as some children who are clearly showing symptomatology both at home and in school may appear normal in the clinic. Although it is helpful to reach a diagnosis, increasingly treatment approaches are focusing on the presence of speciﬁ  c impairments rather than on the pres-
ence of symptoms.
(57)
Three types of psychological interventions have been found of

(57)
Three types of psychological interventions have been found of 
value: ensuring the child’s environment is structured and, when the child is engaged in a task that there is an absence of extraneous, dis-tracting stimuli; counselling to parents and teachers, and behavioural and/or cognitive behavioural approaches directed to the child.
In the classroom the child will beneﬁ  t if seated close to the teacher, 
task demands are kept short and there are interspersed periods of physical exercise. T eachers should be helped to reduce negative interactions by focusing on positive reinforcement for appropriate behaviour however brief this might be. Short periods of timeout before potentially problematic situations get out of hand may reduce the number of painful, angry confrontations. Similar prin-ciples can be applied in the home situation with parents being helped to understand and act on the principles of the identiﬁ  cation

of antecedents that result in problematic behaviour which will then 
have consequences that either increase or reduce the likelihood of recurrence. Positive reinforcement can be provided in the form of star charts, tokens, or other rewards. Training of parents of children with ADHD follows similar lines to training of parents with children with conduct disorder (see above) and, of course, many children show co-morbid ADHD and conduct disorder.

1783
Cognitive behavioural approaches generally aim to achieve 
increased self-control. Most approaches involve encouraging appropriate self-instruction. The child is taught separate steps of self-instruction (‘Stop: What is the problem?—Are there possible plans?—What is the best plan?—Do the plan—Did the plan work?) This approach can be applied when the child is faced with cognitive tasks which would usually be tackled impulsively or to social situa-tions that often result in confrontations, such as arguments with parents or friends.
(58)
The delivery of behavioural treatment to children with ADHD

(58)
The delivery of behavioural treatment to children with ADHD 
presents particular problems. As a group they are slow to respond to conditioning procedures. Their distractibility and short atten-tion span leads to problems in co-operation. Parents are likely to show similar behavioural and cognitive characteristics to their children, so collaboration of parents in treatment regimes may be problematic. The children’s lack of reﬂ  ectivity is a barrier to the use 
of cognitive approaches.
There is no good evidence that cognitive approaches alone are 
signiﬁ  cantly effective in children with severe ADHD.
(59) The most

(59) The most 
thorough evaluation of behavioural approaches to date is the Multi-modal Treatment of Attention-Deficit Hyperactivity Disorder (MTA) study carried out in the 1990s. The 579 children in the study were randomly allocated to one of three conditions: medication with stimulants, intensive behavioural treatment, and a combination of the two. The behavioural approach involved a parent training component, a two-part school intervention and an intensive summer treatment programme. It can therefore hardly be regarded as typical of psychological interventions applied in every-day clinical practice. There were slight advantages to combined treatment over medication alone. Behavioural treatments alone were much less effective for ADHD, though more useful for co-morbid anxiety disorders.
(60) A 9-month follow-up revealed

(60) A 9-month follow-up revealed 
that the effectiveness of behavioural management approaches had been maintained over this period.
(61) Interpretations of the ﬁ  nd-
ings of this study have been divergent. Re-analysis suggests that it may well be that medication alone or in combination with behav-ioural treatment is strongly indicated in severely affected children, while behavioural treatment and parent training are equally effec-tive where impairment is mild or moderate.
(58)
Parent training alone is effective in pre-school children with mild 
or moderately severe ADHD when delivered in a specialist setting, but is not when provided as part of routine primary care by non-specialist nurses.
(62)
Obsessive–compulsive disorders
The core cognitive distortion in children and adolescents with 
obsessive–compulsive disorder (OCD) is thought to lie, as it does with adult patients, in the appraisal of responsibility.
(63) This is

(63) This is 
deﬁ ned as ‘the belief that one has power which is pivotal to bring 
about or prevent subjectively crucial negative outcomes’ . Now we all do have responsibility for our actions; what makes patients with OCD different is that they take upon themselves quite unreason-able levels of responsibility. A 13-year-old might, for example, think ‘I am responsible for making sure my mother does not die’ .This sense of responsibility leads to attempts both to suppress and 
to neutralize the unwelcome thoughts of responsibility.
‘Neutralizing’ is deﬁ  ned as voluntary activity intended to have 
the effect of reducing the perceived responsibility. ‘If I tap on my glass three times before I drink from it, my mother will not die’ . But neutralizing activities increase discomﬁ  ting cognitions and

this leads to further neutralizing activity. Attempts to suppress the intrusive thoughts also increase the likelihood of their recurrence. An additional complicating feature of the cognitive distortion is that, in the mind of the child with OCD, thoughts become imbued with unrealistic or magical powers. It is enough just to have a thought for it to be translated into action, so-called ‘thought-action fusion’ . ‘If I allow myself to think about my mother dying this will mean that she will die’ .
In general the cognitive distortions made by children and adoles-
cents with OCD are similar to those seen in adults. However in a study comparing the various components of OCD cognitions in children, adolescents and adults it was found that children experi-enced fewer intrusive thoughts and these were less distressing and less uncontrollable than those experienced by adolescents and adults.
(64) On the other hand, cognitive processes of thought-action

(64) On the other hand, cognitive processes of thought-action 
fusion, perceived severity of harm, self-doubt and cognitive control were similar across the three age groups.
The aim of cognitive therapy is to help the patient reach the view that obsessional thoughts, however distressing, are irrelevant to any activities that may be undertaken in the future. This is achieved by increasing the patient’s sense of personal efﬁ  cacy, predictability, 
controllability, and self-attributed likelihood of a positive outcome. The techniques used involve the conduct of tasks involving expo-sure to feared stimuli as well as response prevention, stopping the activities that reinforce the unwelcome thoughts.
The most widely applied treatment approach to OCD in children 
and adolescents is that developed by John March and his col leagues.
(65)
The treatment protocol involves 12 sessions of which the ﬁ  rst

(65)
The treatment protocol involves 12 sessions of which the ﬁ  rst 
two are spent on psycho-education and cognitive training and the next 10 sessions on exposure and response prevention with the ﬁ  rst 
and last two sessions, as well as an intermediate session involving parents. The effectiveness of exposure depends on the fact that anxiety diminishes after repeated contact with a feared stimulus. Thus the anxiety of a child worried about germs will be reduced by prolonged contact with a surface the child thinks has germs on it. Encouraging parents not to provide reassurance to children who compulsively and repetitively demand it, removes reinforcement, and results in extinction of the behaviour. Some children become extremely distressed when their parents, on instruction, fail to provide such reassurance; more success is achieved by putting the child in control of reducing parents’ inappropriate behaviour.

Modelling and shaping behaviours are also helpful in giving the 
children or adolescents the skills to expose themselves to feared stimuli. Liberal use of rewards when the child behaves appropri-ately is also helpful in reinforcing desired behaviour.
The most informative ﬁ  ndings on efﬁ  cacy come from the Pediatric 
OCD Treatment study (POTS) T eam.(66) 112 patients aged from 12 
to 17 years, suffering from OCD were divided randomly into four 9.5.3 cognitive behaviour therapies for children and families

SECTION 9  child and adolescent psychiatry 1784
groups: CBT alone, sertraline alone, combined sertraline, and CBT 
treatment and a pill placebo. Both sertraline alone and CBT alone were superior in outcome to pill placebo at 12 weeks after the beginning of treatment. But combined treatment was superior to both treatments administered separately with a clinical remission rate of 54 per cent, compared to 4 per cent for placebo.
Most studies report the results of individual treatment with chil-
dren and adolescents, with limited input from parents. Initial ﬁ  nd-
ings suggest that for middle-school aged children, aged 8–14 years, CBT delivered with a stronger focus on parental involvement than is usually the case with adolescents is effective in reducing symptomatology
(67) at least in the short-term. Success has also 
been reported for similar treatment provided in a group format. Group CBT is as effective as sertraline, and shows better results than sertraline at 9 months follow-up.

(68) The presence of tics does 
not reduce the effectiveness of CBT in the treatment of OCD.(69)
There are few studies investigating the longer-term effect of CBT on OCD. However it has been shown that improvement after both individual and group therapy is maintained for at least 18 months without attenuation.
(70)
Application of CBT for miscellaneous 
purposes
There are a number of other conditions and adverse psychosocial 
situations occurring in childhood and adolescence in which the use of CBT is an important component of management. For a further discussion of these conditions and their management, see other sections of this book.
Chronic fatigue syndrome (CFS)

In this condition, characterized by severe fatigue and overwhelming exhaustion, with excessive sleepiness and a variety of other unex-plained physical complaints, cognitive distortions involving an enhanced tendency to believe in the presence of disease in the absence of medical evidence (illness attribution), and deﬁ  cits in 
the use of problem-solving techniques related to illness and dis-ability have been identiﬁ  ed.
(71) The illness is not uncommon, 
occurring in around 2 per 1000, 11 to 15-year-olds. Rehabilitative methods, including the use of CBT have been found to be success-ful in adults and are also employed in the paediatric age group. A controlled clinical trial has found 10–17-year-olds with CFS to show greater improvement with CBT than a waiting list control group.
(72)

(72)
Cognitive distortions in young people presenting with substance abuse commonly relate to denial they have a serious, ultimately life-threatening problem, unwillingness to believe that effective help is available, and lack of belief in their own self-efﬁ  cacy to change their 
behaviour. There is increasing evidence from controlled clinical trials that cognitive behaviour therapies can achieve positive results.
(73)
Motivational interviewing preceding the use of CBT is important with many children and adolescents and this is likely to be particu-larly the case with those suffering from substance abuse.
Central features of both anorexia nervosa and bulimia nervosa include distorted cognitions about shape and weight. Cognitive behav ioural approaches used with adults with these conditions require modiﬁ  -
cation when used with adolescents, with greater emphasis on involvement of parents.
(74) While CBT is the most effective treat-

ment for bulimia in older adolescents and adults,(75) family coun-
selling is now established as the most effective intervention for 
anorexia nervosa in younger patients.(76)
This condition is characterized by disorders of thinking including repetitive, intrusive thoughts, phobic avoidance of the situation in which the individual was exposed to trauma, ‘survivor guilt’ , and problems in concentration. CBT is the most effective, evidence-based technique in the management in both children and adolescents.
(77,78)
Non-organic pain
Abdominal pain and headache for which no physical cause can be found are commonly seen in primary health care. Although when these conditions occur it is often difﬁ  cult to establish a psychologi-

cal mechanism for the pain, it is reasonably well established that management based on CBT is the most effective approach. CBT is also effective in reducing pain from organic disease as well as in reducing distress when painful paediatric procedures are carried out. For a review of the use of CBT in the management of pain in childhood, see McGrath and Goodman.
(79)
Adverse psychosocial situations
Children and adolescents in adverse psychosocial situations are frequently troubled by distorted perceptions of their predicament. In particular, they may feel themselves responsible for the separa-tion and divorce of their parents or that they have deserved the maltreatment, either physical or sexual, inﬂ  icted on them by adults 
who have abused them. CBT has a signiﬁ  cant part to play in help-

ing children adjust to parental separation and divorce.
(80) It has 
also been shown to have demonstrable value when applied to victims of sexual abuse.
(81)
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1787
9.5.4 Caregiver-mediated 
interventions for children and families
This chapter summarizes interventions that have been developed 
to address child and adolescent behaviour problems and external-izing disorders within the therapeutic milieu of the family. Although it has long been recognized that caregiver-mediated treatments can be employed to address children’s problems, research with families in the past two decades has resulted in numerous systematic, theory-driven approaches that have been subjected to rigorous scientiﬁ  c 
evaluation and have been found to be effective at improving out-comes. Although no intervention is certain to work for every child and it is not possible to engage every family in the intervention process, caregiver-mediated interventions are among the most promising approaches currently available to practitioners.
In recent years, progress in the ﬁ  eld of caregiver-mediated inter-

ventions has included an expansion of the evidence base supporting 
speciﬁ  c intervention practices for use with the general population, 
with high-risk segments of the population (e.g. children in foster care and children in Head Start settings), and with underserved populations (e.g. girls and racial/ethnic minorities). In addition, an increasing emphasis has been placed on the dissemination of proven interventions on large-scale bases within community settings in North America, Europe, and Australia. Evidence is currently being gathered to evaluate the impact of many of these large-scale dissemination efforts. The chapter that follows contains background information on the theoretical underpinnings of caregiver-mediated interventions to address child behaviour problems. Speciﬁ  c interventions that have been developed for chil-
dren in speciﬁ  c age groups—prenatal through early childhood, the

dren in speciﬁ  c age groups—prenatal through early childhood, the 
school-age period, and adolescence—are then described. Finally, we discuss adaptations that have been made to address issues of gender and cultural diversity within this ﬁ  eld.
Before providing a background on caregiver-mediated interven-
tions, a disclaimer is necessary. The term ‘caregiver-mediated’ is employed throughout this chapter, rather than the term ‘family-mediated’ , to convey the sense that these interventions need not occur speciﬁ  cally within the context of the child’s biological family. 
Recognition of the diversity of family types in which children are raised requires a shift from a nuclear family conceptualization to include multigenerational families, lesbian/gay/bisexual families, and other nontraditional family conﬁ  gurations. In addition, many 
children are reared in contexts that include no direct biological 
relatives. For instance, increasing numbers of children are reared in

relatives. For instance, increasing numbers of children are reared in 
foster care. T o a certain extent, this is indicative of the need to address and prevent child maltreatment and to provide services that allow children to remain in their biological families. In addi-tion, it represents a positive development to the extent that many children who have previously been cared for in institutional set-tings are now being placed in community families, which have the potential to provide more adequate rearing environments than institutions. However, it is often the case that caregivers in these foster/adoptive families will require additional support services to improve outcomes for children. Thus, we have adopted the term 
caregiver-mediated interventions to reﬂ  ect the spectrum of exist-
ing rearing environments.
Background on caregiver-mediated 
There is no single predominant cause of the development of

There is no single predominant cause of the development of 
behaviour problems in an individual child. Rather, as is noted in Patterson et al.
(1) research has implicated a broad array of factors 
that contribute to behaviours at virtually every level of analysis. From a societal perspective , factors such as poverty, discrimination, 
and unemployment have been implicated as contributing to higher rates of disruptive behaviour in children. In addition, children in various underprivileged contexts (e.g. children in foster care or with incarcerated parents) show higher rates of disruptive behaviour. Neighbourhood factors  such as crowded living condi-
tions and violence also appear to be associated with higher rates of behaviour problems. At the individual level , psychosocial and

tions and violence also appear to be associated with higher rates of behaviour problems. At the individual level , psychosocial and 
neurobiological factors have been associated with higher rates of behaviour problems. For example, poor social skills, and low cognitive functioning appear to be linked to the development of behaviour problems. Recent evidence also indicates that genetic factors play a role in whether or not a child develops externalizing behaviour.
(2)
With this multitude of factors implicated in the development of 
disruptive behaviour, one might question why caregiver-mediated interventions have become so predominant. The answer is straight-forward. In as much as children exist within the context of their families, caregivers exert the single largest inﬂ  uence on children’s

behavioural and developmental outcomes. Numerous longitudinal studies have shown that caregiver factors predict over and above individual-, neighbourhood-, and society-level variables in deter-mining trajectories towards disruptive behaviour.
(1) Moreover, 
randomized trials of caregiver-mediated interventions have provided information that manipulating caregiver behaviours (e.g. teaching them to use effective parenting strategies) is extremely powerful for improving child outcomes.
(3) Thus, although child behaviour 
prob lems are multidetermined, the most direct method for improving child outcomes appears to be via the caregiver–child relationship.
The interventions that are described below are categorized 
by developmental epoch. It is also important to recognize that interventions exist across the spectrum of risk, including proven interventions to reduce problem behaviours in children with disruptive behaviour disorders and preventive efforts to deﬂ  ect

children from developing disruptive behaviour disorders. An over-all synopsis of the interventions to be described is that they have shown great promise for addressing problems at a number of levels. Although a number of issues still confront the ﬁ  eld, the 
progress that has been made in the last two decades has been 
remarkable in demonstrating that it is possible to address child 
behaviour problems through caregiver-mediated interventions.
Prenatal and early childhood caregiver-mediated 
Caregiver-mediated interventions for the prenatal period through 
infancy and early childhood are generally oriented towards 9.5.4 caregiver-mediated interventions for children and families

SECTION 9  child and adolescent psychiatry 1788
prevention. That is, rather than addressing concurrent problems 
with the child, they are based on the supposition that targeting known precursors of child problems is an effective way to prevent those problems. Among the most inﬂ  uential work in this area has 
been the home visitation programme developed and evaluated by Olds and colleagues to prevent antisocial behaviour in children.
(4)
This project involved a randomized control trial that included longitudinal data collection over more than 25 years.
(5) A total of

(4)
(5) A total of 
400 pregnant women were enrolled in the original study according to one of the three following criteria: under 19 years of age, unmar-ried, or of low socioeconomic status. Those assigned to the inter-vention condition received an average of 9 home visits during pregnancy and an average of 23 home visits between birth and the child’s second birthday. The home visits were conducted by nurses. The focus of visits was upon prenatal and neonatal maternal health behaviours, child care skills, and maternal life issues (e.g. education and employment).
Olds and colleagues reported 15-year outcomes for the children 
of the mothers in this study. Those in the intervention group reported fewer arrests than those in a comparison group.
(6)

(6)
In addition, among those in higher risk categories (as indicated by their mother being both low SES and unmarried at the time of the child’s birth), youth in the intervention group reported lower rates of running away, arrests, criminal convictions and parole violations, and smoking and alcohol consumption than did youth in the comparison group. The authors concluded that this approach may be an effective means of preventing early-onset conduct disor-der, which has been considered the more treatment-resistant and complex form of the disorder.
(1) However, it is also noteworthy

(1) However, it is also noteworthy 
that, in subsequent randomized trial studies to examine how varia-tions in the programme structure affect outcomes, the intervention was found to be less effective when paraprofessionals were used in place of nurses as home visitors.
(7) More recently, and consistent 
with other evidence-based programmes, the emphasis of Olds and colleagues has shifted to a wide-scale dissemination of the inter-vention in community settings.
(8) Within this context, emphasis 
has been placed on maintaining the programme’s effectiveness by developing practices to ensure that the intervention is delivered with high ﬁ  delity to the original model.
It is important to recognize that not all caregiver-mediated pre-

ventive interventions for children in this age group have shown positive effects. For example, the Healthy Start programme was designed to prevent child abuse and neglect, using an initial screen-ing process (usually in hospital settings) to identify families at risk for child maltreatment and employing a home-visitor model of service delivery for the intervention. Although modest positive effects were observed in individual sites implementing this pro-gramme, the overall results from a large-scale randomized trial of this intervention did not support the efﬁ  cacy of the intervention.
(9)
A related problem in the evaluation of the Healthy Start programme 
was low rates of family participation. Of those recruited, many received very few home visitation sessions. With such low dosage rates, it can be difﬁ  cult to determine whether the lack of positive

was low rates of family participation. Of those recruited, many received very few home visitation sessions. With such low dosage rates, it can be difﬁ  cult to determine whether the lack of positive 
intervention effects was due to a failure of the approach to impact targeted behaviours or was due to families receiving too little of the intervention for it to have been effective. Thus, as is true across the span of child development, it is important to consider what the critical elements of effective interventions are and to make sure that these are included in any intervention efforts.Caregiver-mediated interventions in the 
preschool years
The preschool years are marked by a number of important

The preschool years are marked by a number of important 
developmental changes. Dramatic increases in the use of language and physical mobility in addition to an increase in autonomous behaviour provide challenges for many parents. Preschool children need substantial support from parents and caretakers in socializa-tion in their family and school environments. As a result, as with interventions in infancy, the majority of caregiver-mediated inter-ventions at this age are focused on parenting, and the parent–child relationship.
Within the parenting literature, there are many different types 
of parenting skills that have been found to be important in promoting healthy child development. Typically, interventions include a dual focus on increasing positive parenting and decreas-ing negative parenting. Positive parenting usually refers to support-ive, warm, involved parenting that includes praise, positive support, approval, and responsiveness to children and their needs.

(10)
Negative parenting usually refers to parenting deﬁ  cits, including 
poor limit setting, inconsistency, verbal and physical aggression, and harsh discipline.
(11)
Caregiver-based interventions at this age typically focus on 
building a strong positive parent–child relationship in addition to teaching speciﬁ  c behaviour management techniques to promote 
healthy child adjustment and prevent later problems. Although some programmes target at-risk children, such as Head Start children or those with early behaviour problems, there is some evidence that more severe child behaviour problems are related to more limited effects of parent training programmes.
(12)
One of the more successful caregiver-based programmes for pre-
schoolers, The Incredible Years , was developed by Webster-Stratton 
and colleagues.(13) This videotaped programme includes a number

and colleagues.(13) This videotaped programme includes a number 
of salient parenting skills for preschoolers, starting with building a positive parent–child relationship, praise, and rewards and moving to limit setting, problem solving, and discipline. Randomized trial evaluations have suggested that this programme is effective when administered in group and individual settings.
(14) Results have sug-

gested that the programme improves parent–child interactions immediately post-test and 1 year later. The programme was sub-sequently expanded from basic parenting skills to include more advanced parenting, such as anger management, communication, and self-control skills, which is also effective at improving the parent–child relationship and reducing child behaviour problems at short-term follow-up. The advanced programme is able to deal effectively with parent–child problems and the mediators that might inﬂ  uence the parent’s ability to effectively manage the child, 
including depression and the marital relationship. Overall, this parent training programme has been effective with a number of different age groups and populations, including preschool- and school-aged children as well as clinic-referred and community 
Head Start families.
(15)
Other caregiver-mediated interventions involving preschoolers

(15)
Other caregiver-mediated interventions involving preschoolers 
have also shown success at enhancing the parent–child relationship and decreasing child behaviour problems. For example, Parent–
Child Interaction Training (PCIT)  was originally developed for at-
risk children enrolled in Head Start.
(16) Training involved teaching 
parents effective play skills and positive interaction. The pro-gramme has been effective at reducing teacher ratings of behaviour

1789
problems 1 year after the intervention was completed. This 
approach has subsequently been used for other populations. For example, Chafﬁ  n et al . reported on the results of using PCIT  to 
prevent child abuse among families with a history of child welfare system involvement.
(17) The intervention signiﬁ  cantly reduced 
future reports of maltreatment. Interestingly, an enhanced version of the intervention designed to provide individualized services to meet families’ needs was no more effective than the original PCIT
Home visitation programmes in preschool have also shown

Home visitation programmes in preschool have also shown 
promise as effective interventions. Head Start, for example, pro-vides home-visiting services to all families in the programme. The goals of these visits are to work with families on meeting the Head Start performance standards in four areas: education, health–nutrition–mental health, social services, and parent involvement. Research has indicated that children who received home services have shown improvements in the parent–child relationship and early academic achievement compared to children and families 
who did not receive the home visits or parenting model.
(18) Home-
visiting programmes at this age also provide families with social support, self-efﬁ  cacy, and a positive therapeutic relationship with 
the visitor. This relationship serves to enable parents to process and understand parenting and family histories that impede the development of successful parenting skills with their own child.

Caregiver-mediated interventions in the 
school-aged years
As children move into the school years, they face a new set of chal-
lenges at home and in the school environment, including academic achievement, negotiating peer relationships, and the demands of teachers and the school context. At this age, children who have begun developing problems in the context of their families may generalize these problems to the school environment, which is associated with increased risk of later difﬁ  culties in addition to 
problems across multiple domains of functioning.
(19) As a result, 
the transition to school serves as an important target of preventive intervention programmes.
(20) Furthermore, school problems and 
peer difﬁ  culties may exacerbate problems in the home as parents

peer difﬁ  culties may exacerbate problems in the home as parents 
struggle with issues such as homework completion and their child’s social skills and changing peer network. Thus, effective interven-tions aimed at school-aged children must support families and parents through an emphasis on parent training and improving or maintaining academic achievement and positive peer relationships at school.
Although the emphasis on increasing positive parenting skills 
and decreasing negative parenting is typically maintained in inter-ventions at this age and across development, additional components targeting academic achievement, learning and early literacy, and parent–school involvement are important aspects of comprehen-sive, caregiver-mediated interventions for school-aged children. 
There are multiple examples of comprehensive, caregiver-mediated

There are multiple examples of comprehensive, caregiver-mediated 
prevention programmes that have been associated with positive outcomes for school-aged youth and families, including the Families and Schools Together (FAST) Track  programme,
(21)
the Linking the Interests of Families and Teachers (LIFT)  pro-
gramme,(22) and the Schools and Families Educating (SAFE)
Children  programme.(23)
The FAST Track programme began in 1991 and targeted children 
in early elementary school at risk of developing later conduct disorder and delinquent behaviour problems.(21) Children and 
families received a multifocused intervention package targeting development across multiple domains, including peers, the school environment, academic achievement, and the family context. The family intervention integrated successful approaches to parent training regarding the development of school-aged children, including parent–school involvement and early reading.
(21, 24, 25)

Parents met in groups weekly during the ﬁ  rst-grade year and 
bi-weekly in second grade. One hour of parent–child learning activity that emphasized positive parent–child interactions in a controlled environment and early literacy was also provided. Home visits and individualized programming were implemented to meet the special needs of families, such as stress management, marital problems, and maternal depression. The intervention continued through adolescence, with new components adapted to the chang-ing development of children and families. Results of this pro-gramme indicated that it was successful at the end of ﬁ  rst grade 
and third grade in improving outcomes across a number of differ-ent domains, including parenting and child peer relations, emo-tional understanding, and reading skills. Specifically, parents 
showed less physical discipline, more consistent and appropriate 
discipline, and more warmth and positive involvement in their child’s school.
(24, 26, 27)

The LIFT  programme was designed as a preventive intervention 
for at-risk children to decrease the development of conduct prob-lems and delinquency.
(28, 29)LIFT  was designed for ﬁ  rst- and ﬁ  fth-
graders living in at-risk neighbourhoods. Intervention components consisted of a school-based intervention focused on social skills and problem solving, a parent training group, a playground behav-ioural programme, and communication between parents and teachers. Creative intervention techniques were employed to increase parent participation in schooling; for example, a phone answering machine was installed in each classroom, and newslet-ters were sent home to parents about school LIFT  activities. Parents

could call in to the answering machine or leave messages for teachers at any time. This programme was successful at decreasing aggres-sion on the playground and increasing positive behaviours with peers during the year following the intervention. Additionally, the programme was successful at decreasing negative parenting during 
observed mother–child interactions.
(28)
The SAFE Children  programme was administered within differ-
ent schools in high-risk neighbourhoods in the Chicago area with a diverse group of families.
(23) Y outh were randomly assigned within

(23) Y outh were randomly assigned within 
classrooms to receive the intervention, which included parenting and academic tutoring components. The parenting component focused on disseminating information about child development, parenting, skill practice, and home assignments to increase parent-ing skills and on group problem solving around skills when parents needed additional assistance with implementation. The interven-tion targeted children during the transition to elementary school, based on developmental research and theory suggesting that tran-sition points are key points for intervention.
(30) The intervention 
signiﬁ  cantly impacted academic performance and parental involve-
ment in school, with additional outcomes for high-risk families that included higher parental monitoring and reductions in child behaviour problems.

(23)
In summary, effective school-aged, caregiver-mediated inter-
ventions for families are multifocused, typically including foci on parenting skills and school success for children. The majority of 9.5.4 caregiver-mediated interventions for children and families

SECTION 9  child and adolescent psychiatry 1790
successful interventions at this age combine a family component 
with additional interventions to support school adjustment (e.g. social skills training, academic tutoring). Clearly, interventions that target parenting, families, and other domains of children’s functioning are the most efﬁ  cacious interventions to administer 
during the transition to school.
Caregiver-mediated interventions involving 
By adolescence, many youth have achieved a degree of independence 
from their parents and are embedded in the culture of peers, school, and/or their community. The extent of adolescents’ autonomy in today’s world is such that there may be a temptation to consider addressing adolescent mental health problems in a different man-ner than those of younger children. However, among the interven-tions that have demonstrated the biggest impact for adolescents are those focused on youth in the context of their families.
(31)

(31)
The only difference between these programmes and those discussed for younger children is that there is an increased emphasis on parenting skills that are more relevant to adolescent youth, such as problem solving, helping your adolescent gain autonomy, and communication. Adolescents may be more active participants in the interventions that target this age group, attending family sessions and practicing the skills outside of the treatment at home or at school.
There have been a variety of programmes associated with 
positive outcomes for adolescent youth. At this age, effective inter-ventions tend to be brief, family-centred approaches that teach parents the skills needed to parent effectively during adolescence. Caregiver-mediated interventions at this age may be delivered in the school context or in a community centre or clinic. Within the school 
context, several programmes have shown success at decreasing 
adolescent problem behaviour, including substance use over time.

The Adolescent Transitions Program  (ATP) is a caregiver-
mediated treatment for adolescent problem behaviour and sub-stance use. Over the past 15 years, the ATP has been shown to be 
effective in a number of different randomized control trials with parents recruited from the community and schools.
(32,33) The ATP 
curriculum focuses on building a positive parent–adolescent rela-tionship, decreasing known risk factors at this age for problem behaviour (e.g. lack of parental monitoring), and increasing com-munication and listening skills. In the ﬁ  rst series of research studies 
using the ATP , the intervention was delivered in a group format 
and was successful at reducing problem behaviour.
(34) More recently, 
theATP  curriculum has been developed into a caregiver-mediated, 
tailored approach to treatment called the Family Check-Up

tailored approach to treatment called the Family Check-Up 
(FCU ).(31) The FCU  is a preventative intervention based on a health 
maintenance model appropriate for at-risk and high-risk youth. The FCU  incorporates the content from the ATP  curriculum into a 
model that targets parent engagement in treatment. In the FCU
model, families receive a comprehensive, ecological assessment, videotaped observation, and feedback using motivational inter-viewing to engage families in treatment. Across numerous random-ized controlled intervention trials, the FCU  has been shown to be 
effective at reducing teacher-reported risk behaviour, reducing arrest rates, increasing attendance and achievement at school, reducing substance use, and reducing antisocial behaviour.
(35–37)

(35–37)
Interestingly, these outcomes have been mediated by an increase in family management skills, including parental monitoring.
(36)There have been several other comprehensive, caregiver-mediated 
approaches to the treatment of adolescents that have also shown positive outcomes. Many of these models are school-based and preventive, focusing on at-risk and high-risk youth and families via group format from schools. Spoth et al .
(38) examined out-
comes associated with both the Preparing for the Drug Free Years
programme(39) and the Iowa Strengthening Families Program .(40)
Both of these parenting programmes have been hypothesized to

Both of these parenting programmes have been hypothesized to 
reduce the initiation of substance use in the high school years and to reduce antisocial behaviour and were both strength based and focused on teaching parents the skills necessary to prevent adoles-cent problem behaviour. Schools were randomly assigned to deliver the interventions at the school level as universal programmes. Results suggested that these programmes were associated with decreases in the growth of substance use from 6th through 12th grade at the school level. Interestingly, both programmes were brief (up to seven sessions), and effects were found all the way up to 12th grade. These results are promising because they suggest that care-giver-mediated interventions in adolescence can be delivered as universal school-based curricula to decrease problem behaviour in

the school population.
The intervention programmes discussed previously are appro-
priate for typically developing youth, at-risk youth, and high-risk youth. Unfortunately, adolescent youth who have had serious prob-lems with behaviour since early childhood may need caregiver-mediated support that is more intensive and focused around their speciﬁ  c problems. One intervention programme that is particularly 
promising for high-risk youth is Multidimensional Treatment Foster 
Care  (MTFC ).
(3)MTFC  is an alternative to institutional treatment 
for youth with severe emotional and behavioural problems, includ-ing those involved with the juvenile justice system. Within the MTFC
intervention model, youths are placed with foster parents who have received specialized training and who receive a high level of support and supervision from professional staff during the placement. The MTFC  approach includes the use of highly structured behaviour

management programmes as a component of the treatment plan implemented in the foster home. This structure provides the youth with the opportunity to practice the skills that the foster parents are attempting to develop while adjusting the youth’s access to risky situations at a rate that matches the youth’s progress in treatment.
While the youth is in foster care, his/her biological parents receive 
intensive behavioural parent training. As the youth shows signs of 
progress in the foster home, he/she is allowed home visits. The 
duration of these visits is gradually increased, until the child is ready to return home. An extensive aftercare programme ensures that gains are maintained following reuniﬁ  cation.
The MTFC  approach was evaluated via a randomized control 
trial and was found to reduce recidivism, especially in comparison to group care.
(41–43)  Moreover, Chamberlain and Reid reported 
that youth in the MTFC  programme had lower incidences of sub-

stance use and less contact with delinquent peers than youth in institutional settings.
(3) Subsequently, variations of the MTFC
programme have been developed for a variety of populations, including preschoolers
(44–46) and adolescent girls.(47)
Mediators of intervention efﬁ  cacy
There are many commonalities among the intervention pro-
grammes discussed in this chapter. First, each programme is

1791
grounded in developmental research and theory suggesting that 
families are central to the process of intervening in the mental health issues of children and adolescents. Transitions are critical times for intervention, including transitions to school and puber-ty.
(48) Each programme is strength-based, focusing on increasing 
protective factors for children and reducing risks in the environ-ment. Lastly, each programme is multifocused, targeting parenting skills and other important factors in a child’s life that impact development (e.g. academic achievement).
The literature in this area has suggested some common 
themes in the mediators that impact the success of interventions for families. First, recruiting parents into treatment can be difﬁ cult.
(49) Heinrichs et al. examined recruitment issues by exam-
ining participation in parent training groups in their sample of about 600 families using the Triple P  parenting programme.
(50)

(50)
They were only able to recruit 31 per cent of low-income families 
into their parenting groups but were able to retain 77 per cent of families once they began treatment, which included the retention of high-risk families. Similarly, Brody et al. found that having more 
children in the household and youth risk-taking behaviour was related negatively to attendance and engagement in their parenting intervention.
(51) Recruitment and attendance issues have been 
a constant struggle in parenting interventions and have led to the development of brief parenting interventions
(52,53) and more 
tailored, individualized approaches to family treatment.(31) For

tailored, individualized approaches to family treatment.(31) For 
many families, issues such as childcare, work schedules, and the time commitment required to attend parenting groups prohibit participation. In addition, a parent’s interpersonal problems, such as depression and parental resources, can impact participation and outcomes associated with family-based interventions.
(54,55)
Second, culture  plays a key role in the efﬁ  cacy of family interven-
tions. Parenting skills are inextricably connected to cultural values. For example, racial differences are evident in the literature linking parenting practices to child behaviour problems.
(56–58) In previous

(56–58) In previous 
decades, there was an emphasis on cultural sensitivity within inter-ventions targeting diverse groups. Currently, interventions must be not only culturally sensitive but also adapted to meet the needs of the community in which they are implemented.
Several interventions for families have attempted to address 
the issue of culture by providing ecologically valid and culturally sensitive interventions to ethnic minority groups in the United States. For example, the Effective Black Parenting Program
integrated a cognitive behavioural parent training programmewith information of relevance to inner-city African-American families, including discussions of traditional discipline (physical punishment) versus modern discipline (internalizing standards of behaviour).
(59,60)  Components such as helping the child deal 
with racism at school and positive communication about ethnicity

with racism at school and positive communication about ethnicity 
were also included. This programme has been effective at changing parenting behaviour and child behaviour 1 year later.
Another example may be found in the work of Szapocznik and 
colleagues, who have developed a programme to engage Latino families in treatment that includes less traditional forms of engage-ment and more of an emphasis on the ecosystems of families and the cultural context. These researchers have hypothesized that resistance to change occurs during the initial stages of therapy and that traditional forms of engagement may not be successful within the Latino population. Instead, engagement includes joining and encouraging the family to participate in home visits and meetings with signiﬁ  cant family members. This type of engagement strategy 
has been effective in retaining families in treatment with the ﬁ  nal

has been effective in retaining families in treatment with the ﬁ  nal 
goal of reducing drug use and other problem behaviours in adoles-cence.
(61–63)  Although these programmes serve as examples of 
specific approaches to working with populations of different 
cultures, intervention research is just beginning to emphasize these differences and integrate approaches to culturally diverse families into more traditional caregiver training curriculums. More work in this area is clearly necessary, both inside and outside of the United States.
In this chapter, we have attempted to provide a framework for understanding caregiver-mediated, developmentally based interventions for parents and families and to provide examples of interventions that fall within that framework. As is noted previ-ously, the ﬁ  eld of caregiver-mediated interventions and the variety

of interventions available is a much broader topic than has been addressed here. We hope that the information presented here serves both to inform about the speciﬁ  cs of certain interventions and to 
organize the study of the larger ﬁ  eld.
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M.C. Zea). Allyn & Bacon, Boston, MA.9.5.5 Medication for children 
and adolescents: current issues
Problems of mental health and behaviour in children are multidis-

ciplinary in nature and optimal treatment is often multimodal. This article focuses on aspects of psychopharmacology that has special relevance in children and adolescents, especially the recent controversies. In general, this article provides information about classes of medication and not detailed information about speciﬁ  c 
medicines. Treatment recommendations of the speciﬁ  c disorders 
have been dealt within the appropriate chapters.
The use of psychotropic medication in children is higher in the

The use of psychotropic medication in children is higher in the 
United States than in many other countries, and polypharmacy is common. About 1 per cent of overall medical consultations visits by children and adolescents in 2003–2004 in the US resulted in a second-generation antipsychotic (SGA) prescription. The majority of the visits involving antipsychotics were by Caucasian boys aged over nine years, visiting specialists, without private insurance, with a diagnosis of bipolar disorder, psychosis, depression, disruptive disorder, or anxiety.
(1)
Pre-school (2 to 4 year olds) psychotropic medication use, 
between 1995 and 2001 increased across the US for stimulants, antipsychotics, and antidepressants, while the use of anxiolytics, sedatives, hypnotics and anticonvulsants remained stable across these years, suggesting non-psychiatric medical usage.
(2) Ethnicity

(2) Ethnicity 
may influence differential prescription rates; for example, as compared to Caucasian youths, African-American youths are less likely to be prescribed psychotropic medications especially methylphenidate.
(3)
Information assisting 
psychopharmacological decision-making
Apart from a thorough diagnostic assessment, a full medical history 
including present, recent, and past prescribed and over-the-counter medication, response to treatment, and attitude towards interven-tions play a major role in deciding treatment. History of substance misuse needs to be elicited to ascertain potential medication-misuse liability and because certain medication signiﬁ  cantly inter-
act with illicit drugs. A family history of mental illness, suicide, substance abuse, neurological or medical conditions, especially 
early onset coronary artery disease, hyperlipidemias and diabetes, and speciﬁ  cally the response of family members to psychotropic 
medication are all important.

Medication as a part of multimodal 
treatment package
Disorders that have an extended course, where emergence of new 
problems is common, require continuous, dynamic treatment planning and monitoring to ensure effectiveness of the current treatment. The treatment should stress multi-modal intervention and address co-morbid psychiatric disorders. Treatment plans 9.5.5 medication for children and adolescents: current issues

SECTION 9  child and adolescent psychiatry 1794
should be individualized according to the pattern of target symptoms 
and strengths identiﬁ  ed in the evaluation. A thorough functional 
analysis of problems or symptoms is central to pharmacological decision-making. Treatment should target situations in which symptoms cause the most impairment. Custom-designed target symptom scales or daily behavioural report cards are useful in monitoring treatment progress.
One way to conceptualize paediatric psychopharmacotherapy is 
the ‘Symptom-based Approach’ for core symptoms as follows:
◆Symptoms that require and are likely to respond to medication alone : inattention, impulsivity, hyperactivity, tics, obsessions, 
psychotic symptoms, labile mood etc;
◆Symptoms less likely to respond to medication alone, requiring both medication and psychosocial interventions : aggression, rituals, 
self-injury etc;

◆Symptoms that are unlikely to respond to medication that need spe-ciﬁ c remediation or rehabilitation:  skill deﬁ  cits in academic, social, 
or sports domain.
(4)
Psychosocial interventions may be required to address either 
primary or secondary relationship problems associated with the core deﬁ  cits or to deal with co-morbidity.
The ‘art’ of prescribing medication
Pharmacological interventions do not necessarily work exclusively 
because of their ‘neurochemical’ effects. Response to medication also includes the inherent ‘placebo response’ or ‘expectancy effect’ that prescribing can induce, as well as the effect of the ‘therapeutic concordance’ achieved through getting the agreement and acceptance of why the medication is being prescribed and also what is the expected response.

Parents as well as patients respond better when they feel under-
stood, accept why treatment is necessary and are in agreement with the prescriber regarding the need for treatment. Simple strategies help this process: collaborating with parents, patients, school and care providers; giving a clear explanation of diagnoses, of why medication (with or without psychosocial interventions) is neces-sary; setting realistic expectations (for example, aiming for a 
40–60 per cent reduction in anxiety symptoms in a child with

40–60 per cent reduction in anxiety symptoms in a child with 
multiple co-morbidity); keeping track of the larger systems of care at school and home; providing clear, appropriate information sheets, websites etc to obtain further information if needed; prioritizing and tracking target symptoms; asking them to ‘opt in’ to treatment after having weighed all the pros and cons, as opposed to them perceiving that they are being ‘told’ that they ‘have to’ start medication; using short telephone-based medication monitoring during the stabilization phase in order to pick up emerging side-effects and monitoring dosage accordingly; initiating medication using small doses and titrating it up over a period of 4 to 6 weeks, to identify the minimum effective dose (MED) , which is the mini-

mum dose with which ‘acceptable’ improvement with minimal side-effects is achieved; involving school in monitoring symptoms regularly even if it means maintaining a school-home dairy; and willingness to change treatment if the expected outcome has not been achieved.
Domains that each therapy focusses on should be clearly docu-
mented and periodically evaluated. The designation of a case man-ager is essential for chronically disabled individuals to coordinate the wide range of services necessary for their care and to ensure 
periodic diagnostic reassessments.
Developmental issues, pharmacokinetic and 
pharmacodynamic factors affecting pharmacotherapy in children
Generally, drug response may vary with age, weight, sex, disease

Generally, drug response may vary with age, weight, sex, disease 
state, absorption, distribution, metabolism, and excretion. Thus, developmental factors that influence these are important to consider. Although the extent of drug absorption for most medica-tion is similar in children and adults, the rate of absorption may be faster in children and peak levels are reached earlier.
(5)
Absorption is also dependent on the form in which it is adminis-
tered, i.e. liquid versus tablet, and levels peak faster for liquid preparations. Generally speaking, hepatic metabolism is highest during infancy and childhood, 1 to 6 years, approximately twice the adult rate in pre-puberty at six to 10 years, and equivalent to adults by the age of 15.
(5) This is clinically important as younger children

(5) This is clinically important as younger children 
may require higher mg/kg doses of hepatically metabolized medi-cations than older children or adults.
(6)
Adolescence is a period of particularly high ketosteroid levels, 
which have signiﬁ  cant impact on brain neurotransmitter systems. 
A transient decrease in metabolism for some medication has been reported in a few months before puberty, which is believed to be due to the competition for hepatic enzymes with sex hormones.
(7)
Fat distribution varies in children raising during year one then 
gradually falling until puberty and increasing with obesity. Substantial fat stores slow elimination of highly lipo-soluble drugs from the body (e.g. ﬂ  uoxetine and pimozide).
Protein binding and volume of distribution affect the pharma-
cokinetics of medications. These parameters differ in children and have practical clinical implications such as the fraction of the drug that is active and unbound.
(8)This is especially a factor when

(8)This is especially a factor when 
medicating children with eating disorders such as anorexia.
Overall, it is recognized due to the various factors covered in this 
article, non-pharmacological strategies are more effective in pre-schoolers. Pharmacotherapy in school-going children has a reason-able risk/beneﬁ  t ratio and older adolescents behave more like 
adults. As patients mature, treatment plans often must be adapted to change according to the changing individual, family, and envi-ronmental conditions.
Antidepressant efﬁ  cacy
The poor antidepressant response in childhood depression may

The poor antidepressant response in childhood depression may 
have its basis on differences in the hormonal milieu of the brain, and incomplete maturation of the neurotransmitter systems involved in the control of affect, inclusion of adolescents who will over time become bipolar, adolescents with depressive phenocopies, and pos-sible differences in pharmacokinetics and pharmacodynamics. The more rapid hepatic metabolism of imipramine and amitriptyline results in noradrenergically active metabolites, shifting the ratio of the noradrenergic to serotonergic activity of these compounds in children to a ratio higher than that seen in adults. This activity shift is signiﬁ  cant because the noradrenergic system does not fully devel-
op both anatomically and functionally until early adulthood.
(9, 10)
Cardiotoxicity
The maturation of vagal modulation of heart rate increases during the ﬁ  rst decade of life, peaks sometime during the second decade,

1795
and declines gradually with age through the sixth decade of life. 
Sympathetic modulation follows a similar pattern, but rate of maturation of the two branches differ. Furthermore, there is considerable variation between individuals of similar age in auto-nomic maturation. The relative loss of vagal modulation associated with tricyclic antidepressants may be accentuated in some younger subjects because of these maturational factors, leading to cardiotoxicity.
(11)
Stimulants

(11)
Stimulants have been used for decades and good research evidence exists for their short-term use in ADHD. More recently, various stimulant delivery systems have been developed (the osmotic controlled-release system (OROS) – Concerta XL®; the wax-matrix-based beaded system – Metadate CD®; the patch release system – Daytrana®; etc) resulting in long-acting preparations which makes it possible to avoid medication needing to be administered in school. This once daily dosing schedule possibly reduces stigmatization and embarrassment. The release systems and preparation of stimulants (immediate release / slow release ratios) allow the tailoring of the long-acting preparations to suit the need of individual children.
(12)
Precautions with stimulants

(12)
Stimulants are contraindicated in schizophrenia, hyperthyroidism, cardiac arrhythmias, angina pectoris, glaucoma, or a history of hypersensitivity to drug. They can be used with caution in those with hypertension, depression, tics (or family history of T ourette’s syndrome), pervasive developmental disorders or severe intellectual disability. Occasionally tics can be made worse with stimulants.
(a) Rebound effects

It consists of increased excitability, activity, talkativeness, irritability and insomnia beginning 4–15 h after a dose. It may be seen as the last dose of the day wears off or for up to several days after sudden withdrawal of high daily doses of stimulants. This may resemble a worsening of the original symptoms and is encountered frequently by clinicians. Management strategies include increased structure after school, addition of a smaller dose of medication in the late afternoon, use of long-acting formulations or the addition of clonidine or guanfacine to the regime.
(b) Seizures
Methylphenidate can be used in the presence of well-controlled epilepsy. If seizures worsen or emerge during treatment, methyl-phenidate should to be changed to dexamfetamine, which is supposed to increase seizure threshold.
(c) Growth retardation
The MTA study indicates that there is signiﬁ  cant growth reduction 
with stimulant use.(13) It would be advisable not to start stimulants

with stimulant use.(13) It would be advisable not to start stimulants 
in children who are short and are biologically predisposed to short stature (e.g. short parental stature, growth hormone deﬁ ciency etc.).
(d) Cardiac problems
Stimulants may increase pulse rate and rarely can lead to increased 
blood pressure. Importantly, African-American male adolescents may be at a higher risk from mild chronic elevation in blood pres-sure on methylphenidate, needing more rigorous blood pressure monitoring for hypertension than their Caucasian counterparts.
(14)
After several reports of death of patients on Adderall®, there is

(14)
After several reports of death of patients on Adderall®, there is 
currently a warning to clinicians to be aware of possible cardiac side effects, especially in the presence of known cardiovascular illness. The reported rates of sudden death on Adderall® do not exceed reported rates of sudden death on other stimulants or the base rate of sudden death per age group in general off medication.
(e) Abuse potential of stimulants

There is little evidence that substance misuse or dependence results from the prescription of stimulants for ADHD. Self initiated increase in dose by emotionally unstable adults with substance use disorders is possible and needs to be suspected in those who repeat-edly claim to have lost medication or in parents who repeatedly insist that higher doses are necessary to control symptoms, when the child is functioning well in other settings. In such situations it may be better to use long-acting preparations such as Concerta XL®, as the delivery system makes it difﬁ  cult to abuse. Other drugs 
that are useful in this setting are atomoxetine and bupropion.
(f) Psychotic symptoms
Post-marketting surveillance led to enhanced labelling warnings regarding psychosis, mania and hallucinations as adverse events (http://www.fda.gov/ohrms/dockets/ac/06/minutes/2006-4210m_Mi
nutes%20PAC%20March%2022%202006.pdf ). Many such drug-

related psychiatric adverse events may be self-limited and resolve with drug cessation. Stimulants are better avoided in those who have a first degree relative with a psychotic disorder or in children who have psychotic or quasi-psychotic experiences.
Non-stimulants
Atomoxetine  is a non-stimulant noradrenaline reuptake inhibitor, 
which has a high afﬁ  nity and selectivity for the noradrenaline 
reuptake site over serotonin and dopamine transporters. In exten-sive metabolizers (EMs), inhibitors of CYP2D6 e.g. paroxetine, 
ﬂ uoxetine and guanidine  increase atomoxetine steady-state plasma 
concentrations. Atomoxetine is long acting and can be used once a day and does not result in rebound symptom worsening and has little potential for abuse. It does not worsen tics, anxiety or low mood and hence may be useful in some children with ADHD and co-morbid disorders.
(a) Precautions with atomoxetine

Atomoxetine is contraindicated in hepatic insufﬁ  ciency/impair-
ment, glaucoma, uncontrolled seizures or a history of hypersensi-tivity to drug. They can be used with caution in those with hyper-tension or with any condition that may predispose to it, tachycardia, cardiovascular problems in patients with congenital or acquired long QT or a family history of QT prolongation or with cerebrov-ascular disease.
(15)
(b) Growth retardation
Acute treatment studies show that atomoxetine-treated patients lose some weight. Michelson et al. (2004)
(16) reported a change of 
2–3 percentiles in mean height, which appear to be similar to effects observed in stimulant-treated patients. Patients treated for extend-ed periods should be monitored regularly.
(c) Seizure liability
A review of risks and beneﬁ  ts of atomoxetine in 2996 led to warn-

ings on the risk of seizures when taking atomoxetine. It is not to be 9.5.5 medication for children and adolescents: current issues

SECTION 9  child and adolescent psychiatry 1796
used in uncontrolled seizures and should be discontinued in those 
who develop seizures or who experience an increase in frequency of their seizures.
Atomoxetine increases noradrenergic tone and produces increased heart rate and small increases in blood pressure, which subsides on discontinuing atomoxetine. QT interval prolongation can occur but ECG monitoring is not necessary unless one suspects cardiac problems.
(e) Suicidal risk
In September 2005, a ‘black box’ warning was added to the product labelling of atomoxetine as a result of an analyses that showed that suicidal ideation was more frequently observed in clinical trials among children and adolescents treated with atomoxetine (5/1357 [0.37 per cent]) compared to those treated with placebo (0/851[0 per cent]) ( http://www.fda.gov/cder/foi/label/2007/
021411s004s012s013s015s021lbl.pdf ). There was one suicide attempt

021411s004s012s013s015s021lbl.pdf ). There was one suicide attempt 
in the atomoxetine treated group. No completed suicides occurred during these trials. There was, however, no evidence of increased suicidal thoughts in adults taking atomoxetine. Prescribers should monitor for signs of depression, suicidal thoughts or suicidal behaviour and refer for appropriate treatment if necessary.
(f) Hepatic dysfunction
Reports indicate that atomoxetine can cause severe liver injury in rare cases. The spontaneous adverse event database search iden-tiﬁ ed two cases that were probably associated with atomoxetine

Reports indicate that atomoxetine can cause severe liver injury in rare cases. The spontaneous adverse event database search iden-tiﬁ ed two cases that were probably associated with atomoxetine 
use as a cause or contributor to the event. One spontaneously reported case of liver injury (fulminant hepatitis) appeared proba-bly related to atomoxetine therapy by positive re-challenge in a population exposure of about 2.2 million patients within the 2-year period (2002–2004) after approval which is likely to be an underestimate. Less severe liver dysfunction indicated by abnormal liver enzymes is more common and such reactions may occur several months after therapy is started and atomoxetine should be discontinued in patients with jaundice abnormal liver enzyme levels, which should be done upon the ﬁ  rst symptom or sign of 
liver dysfunction (e.g. pruritus, dark urine, jaundice, right upper quadrant tenderness or unexplained ‘ﬂ  u-like’ symptoms).

The pattern of antidepressant use in children and adolescents has 
changed signiﬁ  cantly over the last couple of decades. Tricyclic 
antidepressants were predominantly being used for ADHD, enu-resis, depression, and anxiety disorders during the eighties and early nineties. Over the last 10–15 years, this has changed to pre-dominantly prescribing the newer antidepressants, especially for  anxiety disorders and depression, despite little real evidence for its efﬁ cacy. Current data suggests that other than ﬂ  uoxetine, no other 
antidepressant has evidence to clearly support its use in depression in children and adolescents.
Tricyclic antidepressants

Tricyclic antidepressants include amitriptyline, desipramine, nortriptyline, imipramine, and clomipramine. Historically, they have been used as a second-line pharmacologic treatment for ADHD (though only as an off-licence drug), following stimulant medications. Their use has declined in recent years due to concerns 
of cardiac arrhythmias and case reports of sudden death in the paediatric population. Drawbacks include potential cardiotoxicity, especially in pre-pubertal children, the danger of accidental or intentional overdose, troublesome sedation, anticholinergic side-effects, lowering seizure threshold and possibly declining efﬁ cacy over time.
New generation antidepressants
Fluoxetine, sertraline, ﬂ  uvoxamine, citalopram, escitalopram, and 
paroxetine are all speciﬁ  c serotonin reuptake inhibitors (SSRIs)

paroxetine are all speciﬁ  c serotonin reuptake inhibitors (SSRIs) 
while venlafaxine is a speciﬁ  c noradrenaline and serotonin reuptake 
inhibitor (SNRI) and reboxetine a speciﬁ  c noradrenaline reuptake 
inhibitor (SNI) and mirtazapine. Few trials exist in pre-pubertal children with these drugs; however, the data suggest that the SSRIs have reasonable efﬁ  cacy in severe anxiety disorders such as OCD 
(ﬂ uoxetine, sertraline) but only ﬂ  uoxetine is effective in depression. 
Theoretically, the SNIs may help managing symptoms of ADHD but little research evidence exists.
Precautions with antidepressants
(a) Antidepressant-induced behavioural activation

Frequently children prescribed antidepressants (especially those with developmental disorders or intellectual disability) develop increased motor activity, restlessness, excitability and impulsivity. This usually occurs early in treatment and is often misconstrued as being a manic or hypomanic switch and wrongly treated as if the child had a bipolar disorder. This can be managed by reducing the dose and may need the cover of a benzodiazepine for a few days. This side-effect can be reduced by initiating antidepressants in vulnerable children in small doses (about a fourth of the ﬁ  nal dose 
needed) and gradually increasing the dose over a few weeks.
(b) Antidepressant-related suicidal ideation and behaviour
It was realized two decades ago that imipramine was not effective in pre-pubertal major depression.

(17) The Committee for Safety of 
Medicines (CSM) in December 2003 reviewed all the relevant trials with new generation antidepressants on remission, response to treatment, depression symptom scores, serious adverse events, suicide-related behaviour, and discontinuation of treatment because of adverse events and concluded that the evidence was adequate to establish effectiveness only for ﬂ  uoxetine and contra-
indicated all SSRIs (except fluoxetine) for depressed children (http://www.mhra.gov.uk/home/groups/plp/documents/drugsafe-
tymessage/con019472.pdf ).
(18) This was then followed by the FDA 
asking for black box warnings on all SSRIs warning about the possibility of suicide-related behaviour as a side-effect in depressed children ( http://www.fda.gov/Cder/drug/antidepressants/

SSRIPHA200410.htm ). It is currently advised that children or ado-
lescents being started on or dose being increased of antidepressants should be monitored closely for emergence or worsening of sui-cidal ideation or behaviour.
Recent years have witnessed increased antipsychotic treatment of children despite limited long-term safety data in children. Second generation antipsychotics (SGAs) are the most frequently pre-scribed ones; for example, risperidone, quetiapine, aripiprazole, olanzapine, ziprazidone, and amisulpiride.

1797
Risperidone is the commonest atypical antipsychotic used in 
children and adolescents to manage psychoses and disruptive behaviour in autism. It is a potent dopamine D2 receptor blocker (hence reduces positive symptoms but produces hyperprolactinae-mia) and 5HT-2A receptor blocker (enhances dopamine release in certain brain regions, thus reducing motor side effects and possibly improving cognitive and affective symptoms). The Research Units for Paediatric Psychopharmacology (RUPP) studies have shown that risperidone is effective in managing disruptive behaviours in autism spectrum disorders.
(19) Apart from the side effects of seda-
tion and weight gain, hyperprolactinaemia is common and a few develop extrapyramidal side effects such as tardive dyskinesia.
Aripiprazole  is dopamine partial agonist or dopamine stabilizer,

Aripiprazole  is dopamine partial agonist or dopamine stabilizer, 
used in managing schizophrenia and bipolar disorder. The partial antagonism of D2 receptors reduces dopamine output when dopamine concentrations are high, thus improving positive symp-toms and mediating antipsychotic actions. Blockade of 5HT-2A receptors may cause enhancement of dopamine release in certain brain regions, thus reducing motor side effects and possibly improv-ing cognitive and affective symptoms. Actions at D3 receptors and partial agonism of 5HT-1A receptors could also theoretically contribute to aripiprazole’s efﬁ  cacy.
(20) Even though symptoms 
may improve in the ﬁ  rst week, it is recommended to wait for 
four to six weeks to determine efﬁ  cacy due to the pharmacokinetics

four to six weeks to determine efﬁ  cacy due to the pharmacokinetics 
of the drug. The mean elimination half-life is 75 h of aripiprazole and 94 h for the major metabolite dihydro-aripiprazole and is primarily metabolized by CYP450 2D6 and CYP450 3A4. ketoconazole, ﬂ  uvoxamine, and ﬂ  uoxetine all increase plasma 
levels of aripiprazole, while Carbamazepine decreases plasma levels of aripiprazole. Early experience of aripiprazole suggests that it produces less weight gain, diabetes, or hyperlipidaemia, com-pared to the other SGAs. It is however less sedating and rather acti-vating. Little published evidence exists currently on its use in man-aging non-psychotic disruptive behaviour in developmental disorders but clinical experience suggests that very small doses
(2 to 5 mg per day) are sufﬁ  cient.
Quetiapine  is an effective SGA with moderate effect on weight,

Quetiapine  is an effective SGA with moderate effect on weight, 
but usually needs to be taken at least twice daily because of relative weak receptor binding. Ziprasidone  is being increasingly used and 
is the only SGA that is weight neutral, but has greater impact on cardiac rhythm and QTc interval. Clozapine  is used in those with 
resistant psychoses or those with tardive dyskinesia, but can lead to neutropaenia, sialohorrea, and signiﬁ  cant weight gain. Olanzapine
is used less in children and adolescents because of the propensity to weight gain and metabolic syndrome. Evidence from adults suggests that Clozapine, Olanzapine, and low-potency conven tional antipsychotics such as chlorpromazine are associated with increased risk of insulin resistance, hyperglycaemia, and type 2 diabetes mellitus.
(21, 22)
Precautions with antipsychotics
(a) Movement disorders

(21, 22)
Tardive dyskinesia and extrapyramidal side-effects are more common with conventional antipsychotics. Ethnicity may be a risk factor for dyskinesia in children as African-American children appear to be more prone to tardive dyskinesia when compared to European-American children.
(23) Aripiprazole or clozapine 
are useful in those who require antipsychotics but have developed tardive dyskinesia.(b) Weight gain and metabolic dysfunction
Weight gain is a serious side effect of SGAs and potential conse-quences of obesity include non-compliance with medication and signiﬁ  cant morbidity and mortality.
(c) Risk for SGA-induced metabolic dysfucntion
 High risk  – clozapine, olanzapine
 Moderate risk  – risperidone, quetiapine, sertindole
 Low risk  – amisulpiride, aripiprazole, ziprazidone
(d) Baseline information before starting an SGA
Weigh the children and adolescents and track the BMI during

Low risk  – amisulpiride, aripiprazole, ziprazidone
Weigh the children and adolescents and track the BMI during 
treatment; get baseline personal and family history of obesity, dyslipidaemia, hypertension, and cardiovascular disease; children of parents with total cholesterol >24 mmol/l (parents with high 
BMI), and history of overt heart disease in parent or grandparent at age 55 or younger should be considered to be at high risk; get waist circumference at umbilicus, blood pressure, fasting plasma glucose, and fasting lipid proﬁ  le.
(e) Monitoring after starting an SGA
BMI monthly for three months then quarterly with blood pressure,

BMI monthly for three months then quarterly with blood pressure, 
fasting plasma glucose, fasting lipids within three months and then annually but earlier and more frequently for patients with diabetes or who have gained greater than 5 per cent of initial weight; treat or refer for treatment and consider switching to another atypical antipsychotic for patients who become overweight, obese, pre-diabetic, diabetic, hypertensive, or dyslipidaemic while receiving an atypical antipsychotic. Elevated fasting plasma triglyceride or increased insulin levels may be important signals of potential insulin resistance. Increased low density lipoprotein (LDL) choles-terol and decreased high density lipoprotein (HDL) cholesterol is associated with increased adiposity, especially visceral adiposity. Even in patients without known diabetes, one should be vigilant for the rare but life threatening onset of diabetic ketoacidosis,

which always requires immediate treatment by monitoring for the 
rapid onset of polyuria, polydipsia, weight loss, nausea, vomiting, dehydration, rapid respiration, weakness, clouding of sensorium, and even coma.
Treatment of SGA-induced metabolic dysfunction
Careful selection of treatments taking the metabolic-risk proﬁ  le

Careful selection of treatments taking the metabolic-risk proﬁ  le 
into account, preventative healthy lifestyle counselling, and regular monitoring of body composition and metabolic variables need to become clinical routine. T otal caloric intake is more important than the content of the diet and motivational interviewing and cognitive behavioural techniques can be used to address unhealthy diet, physical inactivity and smoking. Clinically an effective method is to insist that the family (as opposed to only the child) go onto a healthy diet and activity schedule. In fact, informing the parents that they will also be weighed along with the child, helps address this issue effectively. Although preliminary, co-treatment with an SGA plus a mood stabilizer seems to be associated with a greater risk for age-inappropriate weight gain than treatment with one or even two mood stabilizers. A pilot study has shown Metformin therapy is safe and effective in decreasing weight gain, insulin

sensitivity, and abnormal glucose metabolism in children aged 10 to 
17 whose weight had increased by more than 10 per cent during less than one year of olanzapine, risperidone or quetiapine therapy.
(24)9.5.5 medication for children and adolescents: current issues

SECTION 9  child and adolescent psychiatry 1798
Developmentally appropriate monitoring guidelines(25) need to be 
implemented in routine clinical practice and the effectiveness of suggested behavioural and pharmacological interventions should be evaluated.
Mood-stabilizers
Mood stabilizers are usually antiepileptics (except SGAs andlithium) and are used to treat epilepsy or bipolar disorders and occasionally mood lability. Commonly used mood stabilizers include carbamazepine, sodium valproate, lamotrigine, and lithium carbonate. Lithium use warrants regular blood level monitoring, which is often a problem in children. Sodium valproate or valproic 
acid is the most used mood stabilizer and has a reasonable evidence

acid is the most used mood stabilizer and has a reasonable evidence 
base for its use in bipolar disorder. It however should be used very cautiously, if at all, in girls of child-bearing age due to its tera-togenic effects, as well as possible side effect of polycystic ovarian disease. Lamotrigine is a more recent addition and hence being discussed.
Lamotrigine  works by inhibiting effects on sodium channels and 
stabilizes neuronal membranes and thereby moderates the release of excitatory amino acids such as glutamate and aspartate. 
Lamotrigine is especially useful when signiﬁ  cant depressive symp-
toms exist in bipolar disorder.
(26)It has a moderately long half-life,

(26)It has a moderately long half-life, 
especially as monotherapy and can be given once or twice a day. When used with hepatic enzyme inducing medications such as phenytoin and carbamazepine, the half-life is reduced to 12 h. Valproic acid markedly increases the half-life of lamotrigine to 48 to 72 hand the concomitant use of these medications increases the likelihood of developing severe drug rashes including Steven–Johnson syndrome. Lamotrigine is to be started at very low doses (as low as 5 mg/day) and increased slowly over a couple of months. In general, the initiation of this drug requires great patience. Evidence for anti-manic effects is limited.
Rapid tranquilization when managing severe 
maladaptive aggression in children and adolescents
Managing acute severe maladaptive aggression requires a quick

Managing acute severe maladaptive aggression requires a quick 
functional analysis to identify the underlying cause – mood lability, mania, impulsivity, sensory trigger such as hypersensitivity to sound in autism, psychotic experience, autonomic arousal, anxiety or depression etc. The management involves:
◆ ‘Talking down’ as the ﬁ  rst strategy.
◆ The patient should be offered the choice of having an oral 
medication before forcing parental medication.
◆ Oral medication – risperidone 0.5–1mg, or olanzapine 1–2.5 mg 
or lorazepam 0.5–1 mg.
◆ If the above fails, repeat giving either the antipsychotic or the 
benzodiazepine again in 30 min.
◆ If this fails, combine the antipsychotic and benzodiazepine after 
30 min.
◆ If oral treatment is not accepted or has not helped, IV haloperi-

30 min.
dol 1–2 mg or IV diazepam 100–200 mcg/kg or IM haloperidol 1–2mg or IM lorazepam 50–100 mcg/kg can be used.◆ The IV can be repeated after 10 min if not sufﬁ  cient or the IM 
can be repeated after 30 min. Supportive staff and equipment are necessary as side-effects such as cardio-respiratory arrest can occur. Maximum safe doses based on age and weight of the child or 
adolescent should not be exceeded over a 24-hour period .
◆ Physical restraint and seclusion in safe environment may also 
be necessary.
◆ If aggression is occurring in the context of a medical condition
(for example, cardiac delirium leading to pulling out catheters etc), midazolam 500 mcg/kg (max 15 mgs) can be used in the context of the medical setting.
Pharmacological preparation for medical

Pharmacological preparation for medical 
or surgical interventions in children and adolescents with intellectual disability or severe behavioural disorders
Children with intellectual disability or mental health problems

Children with intellectual disability or mental health problems 
should receive the same level of medical care if they are physically unwell, as normal children. As they may not be co-operative, often, physical investigations (for example, MRI or dental X-rays) are avoided or postponed, often leading to late interventions and poorer medical outcomes. If the procedure is a minor one, lasting a few minutes, oral midazolam can be used; if it requires longer or for more serious procedures, an anaesthetist could administer oral ketamine or another general anaesthetic. Simple strategies such as anti-emesis prophylaxis, removal of cannulas before they recover consciousness etc., help minimize difﬁ  culties.
Paediatric pharmacovigilance for psychotropic agents are essential 
and more studies on efﬁ  cacy in this population is necessary. Studies

and more studies on efﬁ  cacy in this population is necessary. Studies 
are urgently required in children and adolescents investigating the metabolic effects of individual medication, especially the SGAs and mood stabilizers, using sex and age adjusted measures of weight and body composition, including fasting blood work and blood pressure measurements, protective factors and long-term follow-up. Until such detailed data become available, it is safe to assume that paediatric populations are at least as or more vulnerable to adverse effects compared to adults. True long-term data is not available currently on most psychotropic agents. Evidence on treatment impact on co-morbid disorders, cost-effectiveness and impact on Quality of Life are sparse and urgently need to be addressed.
Stahl, S. M. (ed.) (2008). Essential Psychopharmacology  (3rd edn). 

Osterheld J.R. and Shader, R.I. (1998). Cytochromes: A primer for child and 
adolescent psychiatrists. Journal of the American Academy of Child and 
Adolescent Psychiatry ,37(4), 447–50.
Martin, A., Scahill, L., Charney, D. S., et al. (2003). Paediatric 
Psychopharmacology—Principles and Update. Oxford University Press, 
New Y ork.
Prescribing unlicensed drugs or using drugs for unlicensed indication 
(1992). Drugs and Therapeutic Bulletin ,30(25), 97–100.

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5. Bourin, M. and Couetoux du T ertre, A. (1992). Pharmacokinetics of 
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in black adolescents. Clinical Pediatrics , (Phila) 27
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9.5.6 Residential care 
for social reasons

Residential care for the young is an elusive object of study. Provided 
in the past by establishments as diverse as workhouses, orphanages, and reformatories, it has no clear deﬁ  nition marking its boundaries 
with foster care or boarding education; at the same time it vari-ously aims to shelter, classify, control, and reform and it has no agreed theory or body of values. The need for residential care, and the difﬁ  culties of providing it, vary with time and place; the issues 
it raises are quite different in Romania than they are in California, or were in Victorian England.
Given this diversity, any discussion of residential care needs to

Given this diversity, any discussion of residential care needs to 
outline the context within which it was written. In the case of this chapter the context is provided by current British social policy. Although the focus is on residential care provided to young people by Children’s Services in England for social reasons, the conclu-
sions drawn are applicable to the rest of the United Kingdom. 
The issues raised by this provision have similarities in other parts of the developed world, in virtually all of which the use of residen-tial care is declining.
(1, 2) This chapter is written against the back-
ground of this decline. Its aims are as follows:
◆ to describe the current characteristics of residential child care in England, and by extension in Great Britain
◆ to outline the problems that have led to its numerical decline

◆ to identify practices that should overcome or reduce these problems
◆ to discuss the role that residential care might play in future.
The characteristics of residential care
In 1979, official statistics for England (the figures for Wales, Scotland, and Northern Ireland are published separately) showed 9.5.6 residential care for social reasons

SECTION 9  child and adolescent psychiatry 1800
that there were approximately 95 000 children in substitute care 
(mainly foster care and residential care). By 2006 this ﬁ  gure had 
dropped to 60 300. While for much of this time numbers in foster care were fairly constant, the numbers in residential care fell from 35 000 to 6 600.
(3) The great bulk of residential care is directly pro-
vided by local authority social services departments (more recently Children’s Services), although provision by the private sector is increasing.
These ﬁ  gures give, in some respects, a misleading impression of the 
numerical importance of homes. The turnover in them is quite rapid—roughly 60 per cent leave a home within 2 months of arrival and just under half the placements result from movements within the care system rather than the breakdown of community care. On average homes still see around three times the number of resi-dents in a year than they accommodate at any one time.
(4) A recent

(4) A recent 
study found that residential care accounted for about 28 per cent of the time that children aged 12 or over spent in the care system.
(5)
The basic characteristics of the local authority homes are well 
known. They are ‘open’ in the sense that the residents are expected to go out to school or work and are not restricted at other times. They are typically small, 50 per cent of them have ﬁ  ve or fewer 
places and the average capacity is around six.
(6) The buildings are 
not markedly institutional, although identiﬁ  able to the practised 
eye, are usually located near to where the residents are likely to live, and aim to take local young people. Staff are non-resident. Many care staff do not possess a recognized appropriate qualiﬁ  cation and 
although government targets in the form of National Minimum Standards
(7) aim to rectify this situation, progress towards these

(7) aim to rectify this situation, progress towards these 
remains relatively slow. Homes have more staff than residents and research has shown substantial variation in the number of care hours delivered for each resident young person each week (between 37 and 254 h).
(6)
Children enter the care system in Britain to be ‘looked after’ 
because of a temporary emergency (for instance hospital admission of the carer) or because of abuse, extremely problematic behaviour on the child’s part, or a breakdown of family relationships. The main characteristics that distinguish residents from other users of substitute care are as follows:
◆ Age: 81 per cent of those who start their period of being ‘looked after’ in local authority homes were aged 10–15 over and about 15 per cent are aged 16 or 17. By contrast, 62 per cent of those entering foster care are under 10 years of age and only 2 per cent are aged 16 or 17.
(8)

(8)
◆ Sex: the proportions of males and females in foster care are roughly equal, but nearly 60 per cent of those in residential care are male.
◆ Geographical location: some local authorities use residential care much more than others. In 2006 the proportions of ‘looked after’ adolescents in residential care varied from just under 3 per cent in one local authority to slightly over 24 per cent in another.
(3)
◆ Behaviour: on average children in residential care exhibit more ‘challenging’ behaviour than do foster children, as reﬂ  ected for 
example in educational performance, measures of psychiatric ill health, delinquency, and the likelihood of being imprisoned as an adult.
(9, 10)
One study(4) carried out as part of a major tranche of research 
on residential child care in England showed that residents had  relatively high levels of school exclusion, truancy, delinquency, vio-

lence towards adults and children, running away, risk-taking sexual behaviour, self-harm, and suicide attempts. Around two-thirds of residents entered ‘care’ for the ﬁ  rst time as teenagers, generally 
because family relationships had broken down, and a further one-ﬁ fth entered because of abuse. They were unwilling to be fostered 
or seen as too disturbed for this. The great majority had previous placements in foster care, residential care, or with relatives.
The role of the homes was to return some as soon as possible to 
their families, attempt to improve the behaviour of others, or pre-pare them for independent living, and to keep a minority (around one-ﬁ  fth) for the foreseeable future. Although there was some 
specialization, most homes attempted to fulﬁ  l all these roles and

specialization, most homes attempted to fulﬁ  l all these roles and 
took all types of resident.
Problems of residential care
Residential care lacks the moral basis that it formerly had; the dis-ciplines and virtues required for successful group life are no longer seen as imperatives. The Children Act 1989 ensured that, except in rare circumstances, young people could no longer be ‘looked after’ simply on the grounds of delinquency when their own welfare and those of others are not at risk.
Theoretical uncertainty accompanies these moral shifts. The 
best-known texts on residential care are now around 25 years old and are dubiously relevant to the current situation where staff no longer live on the premises, and where there have been major changes in stafﬁ  ng, turnover of residents, clientele, and the size and

purpose of homes. In any event, there was never a consensus about which theory should underpin treatment or training. Clear evi-dence for the efﬁ  cacy of any approach has been lacking, whereas 
the evidence for the harmful effects of bad residential care has 
been clear—and frequently repeated on social work courses. Y oung 
people reach residential care as the culmination of a process that marks, and possibly even exacerbates, their social exclusion. Typically, they are disturbed, poorly supported by their families, and lack educational qualiﬁ  cations, a combination which makes 
it difﬁ  cult for them to compete subsequently in the job market or 
to lead happy lives. Descriptions of residential care do not suggest that it mounts the determined attack on these problems that might have some chance of success.
There are particular problems for those young people who leave

There are particular problems for those young people who leave 
residential care to live independently. Residential homes have difﬁ culty in retaining young people until such time as they are 
‘properly launched’ . T o do so would create problems related to cost and to creating a regime suitable at the same time for younger and older teenagers. This means that young people leave care when they are still vulnerable, to cope with lives that are lonely and difﬁ cult, at an age much younger than their better qualiﬁ  ed and 
supported contemporaries leave home. Their transitions to the adult roles of getting an income, maintaining a home, and living with a partner are made earlier than those of others and com-pressed into a shorter period.
(11) Unsurprisingly, they have a much 
higher chance than their contemporaries of becoming lone parents, unemployed, imprisoned, or homeless.
(12,13)
In addition to these problems, there are often pragmatic difﬁ  culties.

(12,13)
◆ Residential care is very expensive; estimated costs are around 
£78 000 per place per year in local authority homes and around £87 000 in the non-statutory sector.
(6) The system costs

1801
 considerably more than foster care or preventive work.(14)
Around 14 per cent of those who enter stay for prolonged peri-
ods and take up half the beds.
◆ Residential homes are prone to scandals involving sexual abuse, outbreaks of disorder, and suicidal behaviour.
(4)
◆ Delinquency and running away are widespread within residen-tial homes.
(4)
◆ There is widespread bullying, sexual harassment, and personal unhappiness.
(4)
Ofﬁ cial reports(15) have emphasized the need to recruit a better 
trained workforce, and there are considerable efforts being made to raise standards in this respect.
(16) However, the proportions 
of qualiﬁ  ed staff remain low and studies that have looked for a rela-
tionship between the proportion of qualiﬁ  ed staff and a measure of 
performance found no association.(4, 6, 13)
Contrary to common belief high staff ratios do not in themselves 
lead to better control in homes or better staff morale or better outcomes, although they do increase costs.

(4, 6, 13)
Improving the quality of residential care
If residential care is to overcome these problems, it will need to reduce the incidence of difﬁ  culties in the home and increase its 
inﬂ uence after residents have left.
In terms of immediate impact, residential homes and schools 
vary widely in the morale of the staff, the incidence of delinquent behaviour and running away, the proportion of residents who avoid going to school, the relationships between staff and residents, and the degree to which the residents report that they are bullied, offered drugs, or feel part of a friendly establishment to which they are committed. These characteristics are far from fully accounted for by intake, and establishments which do ‘well’ in terms of one of them tend to do ‘well’ in terms of the others.
(4, 6, 13)

(4, 6, 13)
These studies suggest the following conditions are required for 
managing homes that are successful in the short-term.
◆ The residential units are either small in size or consist of a large unit divided into small subunits. Such small establishments seem better able to combat the inﬂ  uence of delinquent residents.
◆ The units have clear aims, with which the manager of the home 
is in agreement.
◆ The manager of the home has a clear philosophy on how the young people can be helped, and the staff are in agreement with this outlook.
◆ The residential unit is not based close to the residents’ homes. An emphasis on local placement makes it harder to combat the inﬂ uence of local negative cultures or to maintain a clear focus.
The most recent of these studies
(6) was able to demonstrate the

(6) was able to demonstrate the 
link between these immediate outcomes for young people and the practice of managers of homes. Y oung people experienced better outcomes where managers were accepted as embodying good prac-tice from within a clear ethos, had positive strategies for working with the behaviour and education of young people, and impor-tantly, could enable staff to reﬂ  ect and deploy these. Without 
this bedrock, the systems, procedures, and management targets advocated in reports on the residential system will fail. The basic principle is to establish a set of shared expectations and approaches 
and this is more easily done in a small well-led establishment with a cohesive staff group.
Unfortunately, the ability of homes to affect the behaviour of

Unfortunately, the ability of homes to affect the behaviour of 
residents in the short-term implies that the environments to which residents go next are equally powerful. This has been shown to be the case and creates problems for homes in achieving long-term change. (Evidence on the short- and long-term impact of residen-tial care is discussed in more detail elsewhere.
(4, 6, 13) ) Overcoming 
these problems requires the following:
◆ Reduction of delinquent and problematic behaviour in the home—as noted above these are inﬂ  uenced by the residential 
environment, and there is evidence that they lead to future delinquency.
◆ Encouraging educational achievement and those skills required for ‘success’ in subsequent life and that are relevant to the resi-dent’s subsequent environment—and are seen by the residents as being so.

◆ Working to improve family relationships so that the resident either goes back to an improved family situation or can turn for support to his or her family even though he or she is not living with them.
◆ Providing continuing back-up from the residential home or an aftercare scheme and practical support (e.g. relating to accom-modation).
Success is probably more likely where the home operates on a 
number of fronts simultaneously: seeking to improve skills, learning and educational achievement, and the way the residents see them-selves and also the environment to which the residents return.
Future of residential child care

The case for residential care is essentially three-fold. First, it is able to tolerate behaviour that leads to foster-care placements, the main alternative at the moment, breaking down. Second, a number of young people choose it in preference to foster care. Third, it offers a major resource for adolescents, in preparation for adulthood, in providing supported accommodation, and for those who make a later entry to the care system, such as unaccompanied asylum seek-ing young people. Its future will depend, in part, on the degree to which other provisions can be developed that can match these advantages.
It seems likely that more alternative provision will be developed. 
Some intensive American fostering schemes do appear able to contain young people who are as challenging as those in British children’s homes, and these schemes are being adapted to condi-
tions in the United Kingdom. Some forms of fostering with out-

reach support from respite residential units are in their early stages of development. Remand fostering, ‘crash pads’ , and occasional beds in family centres might provide for some young people currently accommodated brieﬂ  y in children’s homes. Supported 
lodgings could provide for some, particularly older adolescents who avoid foster care because they feel they cannot live in a family, or that it is time that they started to move out on their own. Boarding schools might provide for younger children who do not want to enter foster care because they feel it invites disloyalty to their family, or who enjoy the company of other teenagers. 9.5.6 residential care for social reasons

SECTION 9  child and adolescent psychiatry 1802
The comparative advantages of these differing kinds of provision 
have not been evaluated and it is important that they should be.
The growth of alternative provision will allow the continuing 
reduction of the more traditional residential sector. It is also likely that the sector itself will change, with the current all-purpose children’s home being replaced by more specialist provision that can focus upon clear goals. Research that could determine the shape of such provision is lacking and should be carried out. Possible models of provision include the following:
◆ Secure (namely, closed) provision—public opinion will not allow young people who have committed very serious crimes to remain in open conditions.

◆ Brief- to medium-term provision designed to allow time for young people to consider their situation and move on to new placements in a planned way—there is evidence that fostering placements made from residential care are less likely to disrupt, although it is not yet clear why this is.
◆ Medium-term provision designed to provide treatment—the case for such provision is that treatment involving a group can be more effective. Evidence for this is lacking, although the varia-tions in the behaviour of residents in different establishments is evidence of the power of the group.
In addition to these kinds of residential care, there is a case for

In addition to these kinds of residential care, there is a case for 
some long-stay accommodation in which groups of residents live together. Such provision would be similar to a large foster home or the former family group homes. There seems no reason why it should not work well. It would, however, need to be less generously staffed than current residential homes, otherwise there would be pressure to move residents on for purely economic reasons.
Residential care is very different in different parts of the world. In the United Kingdom it is provided by small community-based homes, who work with an extremely complex and challenging clientele, and face problems associated with high costs, scandal, and frequently a lack of a clear rationale. Despite these difﬁ  culties there 
are wide variations in the performance of such homes, particularly in terms of their immediate impact. Outcomes after the residents have left are harder to inﬂ  uence. However, an approach which com-

bines attention to the residents’ education, behavioural problems, and family environment seems most likely to be effective. In the longer-term, the residential sector is likely to continue to shrink and the part that remains may well need to become more specialized. Research that could guide such developments is presently lacking and should be undertaken.
Department of Health. (1998). Children looked after away from home: 
messages from research . Wiley, Chichester.
Sinclair, I. (2006). Residential care in the UK. In Enhancing the well-being 
of children and families through effective interventions: international evidence for practice  (eds. C. McAuley, P . Pecora, and W. Rose). 
Jessica Kingsley, London.

 1. Gottesman, M. (ed.) (1991). Residential child care: an international 
reader . Whiting and Birch in association with FICE, London. 2. Colton, M. and Hellinckx, W. (eds.) (1993). Child care in the EC .
Arena, Aldershot.
 3. Department for Education and Skills. (2007). Children looked after by 
local authorities, year ending 31 March 2006  (Internet only) Department 
for Education and Skills. http://www.dfes.gov.uk/rsgateway/DB/VOL/v000721/index.shtml
 4. Sinclair, I. and Gibbs, I. (1998). Children’s homes: a study in diversity .
 5. Sinclair, I., Baker, C., Lee, J., et al. (2007). The pursuit of permanence: a 
study of the English care system . Jessica Kingsley, London.
 6. Hicks, L., Gibbs, I., Byford, S., et al. (2007). Managing children’s homes:

 6. Hicks, L., Gibbs, I., Byford, S., et al. (2007). Managing children’s homes: 
developing effective leadership in small organisations . Jessica Kingsley, 
London.
 7. Department of Health. (2002). Children’s homes national minimum 
standards and children’s homes regulations . The Stationery Ofﬁ  ce, 
London.
 8. Department for Education and Skills. (2006). Statistics of education: 
children looked after by local authorities, year ending 31 March 2005, Vol. 1: National Tables . HMSO, Norwich.
 9. Department for Education and Skills. (2006). Care matters: 
transforming the lives of children and young people in care green paper .
The Stationery Ofﬁ  ce, Norwich.
10. Koprowska, J. and Stein, M. (2000). The mental health of looked 
after young people. In Young people and mental health  (eds. P . Aggleton, 
J. Hurry, and I. Warwick). Wiley, Chichester.

11. Biehal, J., Clayden, J., Stein, M., et al. (1995). Moving on: young people 
and leaving care schemes . National Children’s Bureau, London.
12. Anderson, I., Kemp, P .A., and Quilgars, D. (1993). Single homeless 
people . HMSO, London.
13. Berridge, D. and Brodie, I. (1998). Children’s homes revisited . Jessica 
14. Carr-Hill, R.A., Dixon, P ., Mannion, R., et al. (1997). A model of the 
determinants of children’s personal social services . Centre for Health 
Economics, University of Y ork, Y ork.
15. Utting, W. (1991). Children in the public care . HMSO, London.
16. Training Organisation for the Personal Social Services. (2003). 
National occupational standards for registered managers (child care) .
TOPSS, England.
9.5.7 Organization of services

9.5.7 Organization of services 
for children and adolescents with mental health problems
This chapter aims to guide the thinking of practitioners who might 
be involved in developing services to meet the needs of children and young people with mental health difﬁ  culties. Anyone involved 
in this challenging but vital endeavour will need to address the following questions:
◆ Who should the service be for?
◆ What sort of interventions should be provided?
◆ How should the service be structured?

1803
◆ Who should the staff be?
◆ How can the service be made most accessible?
◆ How can service quality be ensured?
This chapter will look at each of these issues in turn to explore 
how each might best be approached.
Who should the service be for?
Ever expanding conceptualization of mental health needs has meant that at least four groups of children are routinely referred to in the discussions about service development in this area:
1 Children and young people in difﬁ  cult (and often terrible) 
circumstances
2 Children at risk of developing diagnosable mental health 
problems
3 Children with diagnosable mental health problems
4 Children with levels of impairment due to mental health 
issues that make it difﬁ  cult for them to function within their 
community/culture
Lack of clarity when discussing the needs of the different groups

Lack of clarity when discussing the needs of the different groups 
can confuse service planning. In particular, it can result in the range of agencies that are all increasingly involved in collaborating in planning provision, talking at cross purposes. When resources are limited (as they generally are for these populations of children, even in the most economically developed countries of the world) it is likely that choices will need to be made about prioritizing between and within these groups. It is therefore vital to be clear at the outset which groups are seen as the priority for a given com-munity and to achieve multi-agency agreement on this.
The needs of each of these groups in relation to service provision 
in this area is considered in turn below.
Children in difﬁ  cult circumstances
Deﬁ nitions of ‘difﬁ  cult circumstances’ vary with national context.

Deﬁ nitions of ‘difﬁ  cult circumstances’ vary with national context. 
The estimated 14 million AIDS orphans (concentrated largely in Africa) would fall into this category as would the 12 million chil-dren in the United States living below the poverty line along with all those children who are in contexts of war, famine, or abuse.
(1)
This group is likely to include those children with high and com-plex mental health needs who are the hardest to reach and who are a policy priority in many areas. However it may also include children who do not have speciﬁ  c mental health needs. Services 
need to ensure they are accessible to these groups where they do have mental health issues but specialist mental health services are unlikely to be the main provider of care for the majority of children in such circumstances.
Children ‘at risk’

Risk factors for developing diagnosable mental health problems include some aspect of difﬁ  cult circumstances (such as violent 
environments, lack of warm family environments) but risk is also heightened by other individual and interpersonal factors such as: brain injury, low birth weight, poor parental mental health, low IQ, irritable temperament, family dysfunction, and the lack of a key supportive relationship with an adult. For children identiﬁ  ed as 
‘at risk’ the focus for mental health provision is likely to be on how to enhance resilience. There may be key opportunities for interven-

tion, such as when the child is born or at key transition points (such as starting school, changing school, leaving school, etc). There is an argument for targeting particular groups such as children of parents with mental health problems. However, evidence for the effectiveness of health promotion and prevention initiatives is still limited and there is some evidence that the promotion of resilience may best be achieved by agencies other than child mental health specialists, such as welfare sectors creating greater neighbourhood cohesion, perinatal services reducing risk of low birth weight and educational services implementing appropriate programmes to promote emotional well-being and support children in times of stress. It is likely that services should only put major resources into targeting ‘at risk’ children if they have sufﬁ  cient resources to meet 
the needs of those children with existing problems.
Children with diagnosable mental health problems

Epidemiological data from Europe and the United States suggests that around 10–20 per cent of children suffer from diagnosable mental health problems (using ICD-10 or DSM-IV criteria). There are indications of differences between countries, with slightly lower rates found in India and Norway, for example, and slightly higher in Brazil, Bangladesh, and Russia. However, not all of these chil-dren need direct service provision. Some diagnosable mental health problems may get better without intervention (such as depressions in mild form). For these reasons, amongst others (in particular the fact that not all current treatments are proven to do more good than harm—as will be discussed below), it is not advised to go down the route recently suggested by the American Psychiatric Association of screening all children in schools and treating all 
diagnosable difﬁ  culties.
(2)

(2)
Children with impairment due to mental 
health difﬁ  culties
It is children in this category who are likely to be the main target 
for specialist child mental health provision. The impact of signiﬁ  -
cant and impairing mental health difﬁ  culties if not effectively 
treated can be substantial. Worldwide, suicide is the third leading cause of death amongst adolescents; major depressive disorder, often starting in adolescence, is associated with substantial psycho-social impairment; conduct disorders amongst children tend to persist into adult life and are reﬂ  ected in later drug abuse, antiso-
cial behaviour, and poor physical health. This group covers a wide variety of children and young people with problems ranging from 
bed-wetting to psychosis. It includes those with chronic and mul-
tiple difﬁ  culties and those with discrete and deﬁ  ned difﬁ  culties. 
It encompasses those with difﬁ  culties where there are known to be

It encompasses those with difﬁ  culties where there are known to be 
effective interventions and those presenting with problems where 
the best course of action is much less clear (as will be discussed 
below). It is this very mixed range of problems that child mental health services must address.
Prioritizing needs
The way needs are prioritized in planning service provision will be heavily inﬂ  uenced by the context in which services are located. 
In some countries independent child mental health provision and unaffordable luxury when pitted against other basic needs. The World Health Organisation
(3) has suggested that where resources 9.5.7 organization of services for children and adolescents with mental health problems

SECTION 9  child and adolescent psychiatry 1804
are particularly limited, priority for funds for child mental health 
provision should be given to those children with existing difﬁ  cul-
ties which are:
◆ occur frequently (and/or have highest cost implications)
◆ cause a high degree of impairment
◆ have the greatest long-term care/cost consequences
◆ have an evidence base for treatment and (particularly in those countries with the most limited resources)
◆ where the difﬁ  culties can be dealt with in primary care or 
universal services such as schools or GPs.
In countries with greater resources, child mental health profession-

als’ input can be conceptualized as being provided at universal, tar-geted, and specialist levels. This involves supporting and working alongside universal provision to promote emotional well-being whether in schools or via primary health care workers. Targeted pro-vision aims to promote emotional well-being in those deemed either at most risk (group 2 above) or in most need (group 1 above) with the groups being determined by policy imperatives. Here specialist men-tal health professionals will work alongside workers from other sec-tors who take a lead in relation to the needs of these groups as a whole, such as social welfare workers and primary care staff. Specialist provi-sion aims to intervene primarily with those with existing impairment due to mental health difﬁ  culties (group 4 above) and can be provided

at a local community level, though for more rare and specialized resources may be provided at a regional ore even at a national level.
Weighing mental health promotion initiatives against interven-
tions for those with existing impairments requires particularly 
careful thought. Whilst there is evidence that promotion pro-
grammes may sometimes promote emotional well-being, research to date has not proved that this will reduce levels of signiﬁ  cant dis-
turbance and thus impact on specialist services, nor that such pro-grammes are necessarily the most effective approach. It therefore does not seem warranted at this stage to assume that investment in prevention can be done at the expense of investment in services for those with existing impairing mental health difﬁ  culties.
In planning response to ‘need’ , it is also important to consider the

In planning response to ‘need’ , it is also important to consider the 
potential negative and even harmful impact of increased specialist mental health services. Mental health professionals are frequently in danger of assuming that more specialist mental health provision is unquestionably an unalloyed good. The need for more provision must be set in the context of other (sometimes competing) ‘needs’ , such as: the primary need of children to be nourished, sheltered, and protected; their need not to be stigmatized or miss education; and their need not to receive inappropriate, ineffective, or harmful treatment. At times an inappropriate mental health focus can be an unhelpful drain on resources. One documented example is when well-meaning voluntary groups entered a country following a disaster to provide ‘interventions for PTSD’ that were not linked to other relief efforts and actually interfered with and undermined key initiatives.

(1) Whilst the costs of not providing effective special-
ist mental health inputs can be high, it is important to remember there are also costs to providing unhelpful services.
What sort of interventions should 
be provided?
As yet, few services have been developed on the basis of considered 
evidence. Systems of care in CAMHS (as for many areas in health care) have historically been developed on the basis of beliefs, asser-
tion, and innovation within the limits of given structures but with little reference to the slowly and tentatively emerging evidence base. The arguments for trying to promote evidence-based service development are compelling. Natural biases in reasoning mean that people tend to make decisions based more on things that ﬁ  t 
their assumptive world view than those that challenge it and are more inﬂ  uenced by the charisma of those promoting a particular

their assumptive world view than those that challenge it and are more inﬂ  uenced by the charisma of those promoting a particular 
approach than by evidence for its effectiveness. When the evidence base is not used as the basis for service development, it makes it more likely that seemingly plausible but ineffective and/or harmful interventions may be introduced or continued and that new inter-ventions that have been shown to do more good than harm may never be introduced.
(4)
The evidence base in relation to child mental health interven-

(4)
tions, whilst growing, is still limited both in extent and quality. Shortcomings include the sheer paucity of studies, the fact that most research is conducted in United States and there is lack of agreement over appropriate outcome measures. Even where inter-ventions have been found to work in academic studies they are generally not as effective when applied in ‘real life’ settings. This difference may be due to differences in the populations of children seen, types of interventions made, and/or outcomes assessed. There is increasing evidence of the necessity of carefully implementing all aspects of a particular intervention if it is to be as helpful, and that lack of ‘ﬁ  delity to model’ may account for the lack of generaliz-
ability of some of the interventions. On the other hand, the role of non-speciﬁ  c factors such as therapeutic engagement, expectations of

ability of some of the interventions. On the other hand, the role of non-speciﬁ  c factors such as therapeutic engagement, expectations of 
change and therapist warmth may need to be taken into account.
(5)
Whilst bearing these limitations of the research evidence base 
in mind there is an emerging consensus in relation to some key interventions
(6–8) and increasing attempts to develop guidance for 
practitioners based on the evidence in this area are being developed (e.g. National Institute of Clinical Excellence guidelines in England, American Psychiatric Association Practice parameters in the United States). Those interested in the detail of the sorts of interventions currently found by the evidence base to be most efﬁ  cacious should 
go to these guidelines and may also be interested in attempts to summarize the evidence base
(8, 9) (condenses current ﬁ  ndings to 
inform the work of practitioners and others and is freely available via the internet).

It is hoped that as the evidence base develops, so should the sophis-
tication with which it might be interrogated. For every intervention listed above as having ‘good evidence’ to support it, the following questions should be asked (modiﬁ  ed from Kazdin
(10), p. 113):
◆ What are the costs, risks, and beneﬁ  ts of this intervention relative 
to no intervention?
to other interventions?
◆ What are the key components that appear to contribute to posi-
tive outcomes?
◆ What parameters can be varied to improve outcomes (e.g. includ-ing addition of other interventions, non-specific clinical skills, etc)?
◆ T o what extent are effects of interventions generalizable across (a) problem areas, (b) settings, (c) populations of children, and (d) other relevant domains?

1805
We are a long way from being able to answer these questions in 
relation to CAMHS currently but it is to be hoped that this will develop with time.
However, even as the evidence base grows from academic studies 
this must still be treated with caution. It is not suggested that ﬁ ndings from even the most rigorously undertaken randomized 
controlled trials can necessarily be applied wholesale to all indi-viduals with similar problems. The full context of an individual’s 
range of needs and circumstances must be taken into account and 
it is also hoped that understanding of the academic literature will be supplemented with a growing evidence base emerging from practitioners own routine evaluation of their own work (see dis-cussion in ‘ensuring service quality’ section below).
How should the service be structured?
If the evidence base for types of intervention is limited, this is even more so for types of organization.
The ‘Fort Bragg Study’ (and the subsequent Stark County

The ‘Fort Bragg Study’ (and the subsequent Stark County 
Study) conducted by Bickman and colleagues in the United States warrants particular attention as they generated such high levels of interest and controversy. This study evaluated a large-scale sys-tem change project designed to improve outcomes by providing an unrestricted set of coordinated inputs from a range of servic-es. Results were compared with other sites using traditional ser-vices. Information was collected on service use, cost, satisfaction, clinical, and functional data over the course of the 3-year study and at follow-up since. The study found greater access and increased rates of satisfaction and less use of inpatient services, but no differences in behavioural–emotional functioning overall 
and the cost was much greater at Fort Bragg. The subsequent

and the cost was much greater at Fort Bragg. The subsequent 
Stark County Study also found that a multi-agency system for care led to no signiﬁ  cant difference in clinical outcomes when 
compared with routine services. Bickman concluded ‘the current national policy of large investments in systems of care infrastruc-ture is unlikely to affect children in the manner intended . . . we need to focus on the services or treatments themselves to improve outcomes’ .
(11)
This conclusion has been hotly contested. Flaws in the study

(11)
This conclusion has been hotly contested. Flaws in the study 
design, implementation, and interpretation have been highlighted. It was argued that services were overwhelmed in the early months and provided less effective interventions, that the researchers failed to take into account some of the positive outcomes on some of the measures used and so on. It has been suggested that there is evidence that ‘wrap around services’ (whereby a range of services are provided in a coordinated fashion to children and families based on their needs and not those of the services) do produce better outcomes and that the poor results above may have been due to lack of ﬁ  delity to this model.
(12)
There is some evidence that shared understandings at the highest 
level and pooled budgets seem to be crucial to positive multi-agen-cy collaboration. ‘MHSPY’ in the United States is an initiative that involves ﬁ  ve public and two private agencies who have come

level and pooled budgets seem to be crucial to positive multi-agen-cy collaboration. ‘MHSPY’ in the United States is an initiative that involves ﬁ  ve public and two private agencies who have come 
together with blended funding to provide a coordinated focus on a group of ‘at risk’ and ill children and where outcomes look positive though lacking a control group or clear cost-effectiveness data as yet.
There is little evidence available currently to guide service 
developers as to the best way to structure services in relation to a number of other key issues, such as: what age of children should be seen by different services? Is it best to structure services around 
particular problems or around different age groups? What should be the balance between inpatient and outpatient provision? Whilst it is hoped that with time, more evidence will emerge in relation to these issues, it may be hypothesized that, here too, non-speciﬁ  c

factors, may be relevant. Thus the leadership skills of the clinicians who establish a given service, the strength of their commitment in a particular shape of service, and the ability of key individuals to collaborate across whatever boundaries are inevitably created, may impact as much, if not more, than the speciﬁ  cs of different forms 
of service structure.
Who should the staff be?
In terms of who the key staff should be who provide specialist mental health services for children, whilst there is much assertion and rhetoric as to what is the ideal workforce composition and an emphasis on multi-disciplinary and multi-agency team develop-ment wherever possible, there is, in fact, very little hard evidence as to what an ideal workforce should look like.
In many parts of the world specialist mental health professionals

In many parts of the world specialist mental health professionals 
are in short supply, and there is an increasing focus on capitalizing on opportunities for mental health provision to piggyback on other sectors with more provision (such as HIV programmes in Africa or schools in many areas of the world). The potential contribution of paediatricians, primary care workers, and teachers is increas-ingly recognized, though care must be taken not to overload already stretched systems and research highlighting the importance of ‘ﬁ delity to model’ (as discussed above) suggest that there may 
be a necessary threshold of amount of training combined with ongoing organizational support, for subsequent interventions to be 
How can the service be made 
most accessible?
Attempts to make provision more accessible as well as less stig-

matizing can include use of education and primary care workers, community and religious leaders, and family networks. There is evidence that linking with relevant belief systems of the commu-nity, such as ayurvedic treatment and yoga in parts of India, may be crucial, and that providing training for traditional healers may help increase child mental health capacity. The work of vol-untary organizations can be a major source of innovation and energy and communities need to ﬁ  nd ways for statutory services 
to learn from them. For example the walk in community centre, Empilwent in South Africa pioneered a more accessible drop in approach.
It could be argued that child mental health services have been 
slow on the whole to ‘get out of the clinic’ and in particular to 
embrace the impact of new technologies that might increase access.

embrace the impact of new technologies that might increase access. 
However some interesting innovations are developing. These range from mobile services such as the peripatetic child mental health team which travels across Germany providing follow-up on previ-ously hospitalized young people, providing new consultations, and supervision of institutions for children
(13) to increased use of 
telephone and text contact generally, and telephone helplines and websites speciﬁ  cally.
T elephone helplines such as ‘Kids Help’
(14) in Australia, 
‘Childline’(15) in the United Kingdom, and ‘Parents Information 9.5.7 organization of services for children and adolescents with mental health problems

SECTION 9  child and adolescent psychiatry 1806
Service’ (Y oungMinds Parent Information Service)(16) in the United 
Kingdom, are often run by charities independent of statutory provision but it may be in the future that greater links can be made by such resources and more traditional services. ‘T elefono Azzuro’ of Italy shows the way these can be combined with other provisions.
(13)
A range of websites have been developed by and for young 
people some of which allow for discussions between young people and others offer access to specialist advice and support (e.g. ‘ru-ok.com’).
(17) The use of emails and text messaging to communicate 
between professionals and young people is now increasing as are the use of IT aids to assessment and treatment and the pace of innovation in this area is likely to accelerate sharply in the future.
How can service quality be ensured?

The implementation of routine outcome evaluation is likely to be a crucial factor in ensuring service quality. There are increasing attempts to ensure routine outcome evaluation is in place. The CAMHS Outcome Research Consortium (CORC)
(18) (chaired by 
the author) is collaboration between over half of all services across the United Kingdom who are implementing an agreed model of routine outcome and agreeing jointly ways to present the data in order to inform service providers and users and to help inform service developments (CORC).
(8) The approach has parallels with

(8) The approach has parallels with 
that being employed in the United States and Australia. In all cases a small suite of measures is completed by service users and provid-ers at initial contact and at some time(s) later. Increasingly models are being developed whereby individual practitioners evaluate outcomes over the course of treatment which can be immediately compared with outcomes from others with similar difﬁ  culties at 
the outset, allowing practitioners to get feedback about progress relative to others.
For child mental health service to institute routine outcome 
evaluation and to develop into self-reﬂ  ective and learning organiza-
tions, requires functioning IT systems and an agreed core dataset.
(19)
There are now datasets for child mental health emerging in some countries.
(20) But even in the most developed countries, the prom-

(19)
ise of coherent IT systems, remains more a hope than a reality. It is key that IT systems develop that are capable of supporting decision-making by providing easy access to information for prac-titioners so that they can get feedback on their work and learn accordingly.
There is an increasing emphasis on the importance of involve-
ment of service users to inform service development priorities and to be part of any evaluation of services, to ensure quality. Some innovative models have been tried such as in Ohio which has created outcome systems from service user perspective and in parts of the United Kingdom where young people are trained as service evaluators though again the impact of these on quality of services in the future is yet to be researched.

There is no one ideal model for organizing services, however some key principles can be identiﬁ  ed:
1 It is helpful to start with an analysis of the range of anticipated 
needs, and to seek clarity as to the current priorities for a given community. 2 Where resources are limited, specialist mental health pro-
vision should be targeted foremost on those with greatest levels of impairment for whom there are the most effective interventions.
 3 Implementation of effective models of prevention and pro-
motion should be supported so far as resources allow and not at the expense of provision for those with existing difﬁ  culties.
 4 The existing evidence base in relation to effective interventions 
and models of delivery should be seen as a starting point for practice, though the limitations of the evidence base should be held in mind.
 5 Successful service development is likely to rest on collaboration

5 Successful service development is likely to rest on collaboration 
across health, social care, and education—using pooled budgets where possible.
 6 Good information gathering systems are needed that allow 
individual practitioners and managers to audit and review work.
 7 Staff members should be encouraged to adapt their practice in 
the light of the emerging evidence from literature and their own outcomes rather than retaining allegiance to any one theoretical model or framework.
 8 Collaborations between service providers that focus on devel-
oping best practice may be of help.
 9 The input and involvement of service users may be of relevance 
in helping develop accessible and acceptable services.
10 Remember not all service developments are benign—always 
weigh up possible harm that may be caused as well as potential for good.
Wolpert, M., Fuggle, P ., Cottrell, D., et al. (2006). Drawing on the

Wolpert, M., Fuggle, P ., Cottrell, D., et al. (2006). Drawing on the 
evidence: advice for mental health professionals working with children and adolescents-revised version  (Child and Adolescent Mental 
Health Services Evidence Based Practice Unit-University College London) http://www.ucl.ac.uk/clinical-health-psychology/pdf Files/
DotEBooklet2006.pdf
Wolpert, M. (2008). Organisation of services for children and adolescents 
with mental health problems. In Rutter’s child and adolescent psychiatry ,
(eds. M. Rutter, D. Bishop, D. Pine, et al. ) Blackwell, Oxford.
Oxford.
1. World Health Organization. (2005). Atlas: child and adolescent mental 
health resources. Global concerns: implications for the future . World 

Oxford.
2. American Psychiatric Association. (2002). Quality indicators-deﬁ  ning 
and measuring quality in psychiatric care for adults and children.American Psychiatric Association.
3. World Health Organization. (2003). Caring for children and adolescents 
with mental disorders: setting WHO directions . World Health 
4. Gray, M.J.A. (2001). Evidence-based healthcare: how to make health policy 
and management decisions . Churchill Livingstone, Edinburgh.
5. Fonagy, P ., Target, M., Cottrell, D., et al. (2002). What works for whom? A 
critical review of treatments for children and adolescents . Guilford Press, 
London.

1807
 6. Goodman, R. and Scott, S. (2005). Child psychiatry  (2nd edn). 
 7. Rutter, M., Tizard, J., and Whitmore, K. (1970). Education, health and 
behaviour . Longman, London.
 8. Wolpert, M., Fuggle, P ., Cottrell, D., et al. (2006). Drawing on 
the evidence: advice for mental health professionals working with children and adolescents-revised version  (Child and Adolescent 
Mental Health Services Evidence Based Practice Unit-University College London) http://www.annafreudcentre.org/dote_booklet_2006.pdf
 9. CAMHS publications, London. (2007). Choosing what’s best for you. 
What scientists have found helps children and young people who are sad, worried or troubled. http://www.annafreudcentre.org/ebpu/choosing.pdf
10. Kazdin, A.E. (2004). Evidence-based psychotherapies for children 
and adolescents: strategies, strengths and limitations. In Facilitating

and adolescents: strategies, strengths and limitations. In Facilitating 
pathways: care, treatment and prevention in child and adolescent mental health  (eds. H. Remschmidt, M. Belfer, and I. Goodyer), pp. 103–18. 
Springer-Verlag, Berlin.
11. Bickman, L., Lambert, E.W., Andrade, A.R., et al. (2000). The Fort 
Bragg continuum of care for children and adolescents: mental health outcomes over 5 years. Journal of Consulting and Clinical Psychology ,
68(4), 710–6.
12. Bruns, E.J., Burchard, J.D., Suter, J.C., et al. (2005). Measuring ﬁ  delity 
within community treatments for children and families. In Outcomes
for children and youth with emotional and behavioral disorders and their families , Vol. 2 (eds. M. Epstein, A. Duchnowski, and K. Kutash). 
Pro-ED, Austin, TX.
13. Remschmidt, H., Belfer, M., and Goodyer, I. (eds.) (2004). Facilitating 
pathways: care, treatment and prevention in child and adolescent mental

pathways: care, treatment and prevention in child and adolescent mental 
health . Springer-Verlag, Berlin.
14. Kids Help Line. http://www.kidshelp.com.au/home_KHL.aspx?s=6
15. Childline. http://www.childline.org.uk/
16. Y oungMinds’ Parents Information Service. http://www.youngminds.
org.uk/parents
17. RU-OK.Com. http://www.ru-ok.com/
18. CAMHS Outcome Research Consortium. (CORC). http://www.corc.
uk.net
19. Wolpert, M., Bartholomew, R., Domb, Y., et al. (2005). C ollaborating 
to improve Child Mental Health Services. CAMHS outcome research consortium handbook. Version1.  CORC, London.
20. http://www.ic.nhs.uk/our-services/standards-and-classiﬁ  cations/
dataset-list/camhs
9.5.8 The management 
of child and adolescent psychiatric emergencies
Gillian C. Forrest
‘Child’ is used throughout this chapter to refer to anyone aged

‘Child’ is used throughout this chapter to refer to anyone aged 
under 18, to avoid the repetition of ‘child or young person’. ‘His’ and ‘her’ are used interchangeably.
This chapter provides a practical approach to the management of psy-chiatric emergencies in children and adolescents. Such emergencies are challenging for a number of reasons. The professional resources 
available are usually very limited, and there is often confusion or even disagreement between professionals over what constitutes a psychiatric, as opposed to a social emergency. The parents or carers play a key role in the situation and need to be engaged and involved appropriately in the assessment and manage-ment; and issues of conﬁ  dentiality and consent need to be taken 
into account. In addition, the psychiatrist may ﬁ  nd himself or

into account. In addition, the psychiatrist may ﬁ  nd himself or 
herself working in a variety of settings—the child’s home, a hospi-tal emergency department (A and E), a police station, a children’s home, or residential school—where the facilities for assessing an angry, disturbed, or upset child may be far from ideal.
Most emergencies occurring in community settings involve 
externalizing behaviours: aggression, violence; deliberate self-harm, or threats of harm to self or others; or extreme emotional out-bursts.
(1,2) Some will involve bizarre behaviour which could be an 
indication of serious mental illness or intoxication by drugs or alcohol, or a combination of both. The emergency situation often arises in the context of acute family conﬂ  ict or distress.
Frequently other agencies are involved before the psychiatrist is

Frequently other agencies are involved before the psychiatrist is 
called in (for example, emergency room staff, social workers, or the police). The on-call psychiatrist needs to be familiar with or able to obtain immediate advice about his or her local child and adolescent psychiatric services, the local child protection and child care procedures, and with the relevant mental health and child care legislation.
Vignette 1:
A 12-year-old boy is in the police station, after attacking a neighbour 
and smashing a window. He punched a police ofﬁ  cer when they tried 
to pacify him. He has refused to talk to the police, and is sweating and dishevelled, pacing up and down and muttering to himself. The police think he is psychotic. The neighbour is in the waiting room; his father has been called back from work.
After obtaining the history of the incident from the neighbour and

After obtaining the history of the incident from the neighbour and 
the police, the psychiatrist interviewed the father. The boy had been diagnosed with an autistic spectrum disorder when he was 5. He was easily upset by any change of routine. His mother had gone away for a few days, leaving him in the care of a neighbour while his father was at work. This aggressive outburst was precipitated by the neighbour refusing to let him watch his favourite video. The boy calmed down with his father and a mental state assessment conﬁ  rmed autistic fea-
tures but no psychotic symptoms. The psychiatrist persuaded the neighbour and the police to drop charges and the boy was allowed to return home. The family were offered an out-patient appointment but declined this, and arrangements were made for his General Practitioner (GP) to review the situation in a few days’ time.
Vignette 2:

A 15-year-old girl has locked herself in the bathroom at home with a carving knife and is threatening to cut her wrists. Her parents have been unable to persuade her to come out and are now distraught. The GP was called but she refuses to speak to him.†
When the psychiatrist arrived, he asked the family to withdraw so that 
he could talk to the girl through the bathroom door. She was very upset and described how she had been dumped by her boyfriend ear-lier that day, had had a row with her step-mother about a large phone bill, and now felt that she didn’t want to live any more. The psychia-trist persuaded her to come out to talk things over with her parents. There was no evidence of a depressive disorder and after the psychia-trist helped the girl share her distress about her boyfriend with her 9.5.8 the management of child and adolescent psychiatric emergencies

SECTION 9  child and adolescent psychiatry 1808
parents, she calmed down. There was a history of one previous attempt 
at self-harm, also connected with peer relationship difﬁ  culties, and 
the psychiatrist felt that there were some underpinning issues around family communication. He offered the family an out-patient appoint-ment to explore these further.
In the emergency situation, the role of the psychiatrist is to:
◆ assess the disturbed behaviour
◆ make a diagnostic formulation which distinguishes behaviour associated with mental illness from that which is a reaction to an upsetting event or situation
◆ produce a care plan to manage the situation safely and effectively in the short-term.
A step-by-step approach to the management of child and adoles-
cent emergencies is described here. The management of deliberate self-harm is dealt with in Chapter 9.2.10.
Step 1. Gathering information

Before attempting to assess the child and his or her family, it is very important to gather as much background information as possible about the incident or behaviour from any professionals who have been directly involved. They may be able to give an accurate 
description of the child’s behaviour and any incident which pre-ceded it; or useful background information about the family. Take time to read any notes that are available; and talk to those involved (GP , police, paediatric staff, A and E staff, etc.).
Step 2. Interview with the child/young 
person
Although this is described ﬁ  rst, parents may expect to be seen 
before the child, or it may be preferable to talk to them ﬁ  rst to 
gather background information (see Step 3).
A disturbed or upset child in this situation will be wary of any

A disturbed or upset child in this situation will be wary of any 
stranger, and the more out of control they are, emotionally and behaviourally, the more likely they are to be uncooperative initially. The psychiatrist needs to calmly establish that they have come to try and help the child, that they are non-judgemental and that they can be trusted. She should always ask to see the child alone, to establish a conﬁ  dential relationship, and to be able to assess the 
child without the inﬂ  uence of parents.
Honest and open communication is essential, especially if there is 
any possibility of child protection issues. Often the child is terriﬁ  ed Fig. 9.5.8.1 Flow chart of management of child and adolescent psychiatric emergencies.Emergency call out to home or community setting
Information from referrer/other professionals/notes
Diagnostic formulation

Mental illness Acute behavioural disturbance Child abuse
Danger to self /others Settles with interview Child Protection procedures
Ye s No Y es No Home Admit place of safety
admit medication + advice advice sedate
call policechange envt
review early review OPD FU by GP /OPD/ SSDObserve +  interview child Interview parents/carers

1809
that they are going to be forcibly taken away from their home or 
family (a desperate and angry parent will often threaten this), and this fear may need to be addressed before the assessment can begin.
A useful approach is to say to the child: ‘I’m Dr ….. I’m a 
psychiatrist who sees children and young people with all sorts of worries and troubles. I’ve come to see you now, to try and under-stand what this is all about, and see if I can ﬁ  nd a way to help’ .
If the child refuses to talk at this stage, they may be angry, 
mistrustful, or psychotically withdrawn. Patience is required to see if this can be overcome by convincing the child that you have come to listen to them and not to ‘take them away’ . Reﬂ  ecting back to the 
child how you perceive their emotional state may also help. For 
example, the psychiatrist might say: ‘Y ou are obviously very upset

example, the psychiatrist might say: ‘Y ou are obviously very upset 
and angry. I wonder what it is that’s made you feel this way’ . Sometimes children will choose to communicate by writing notes or drawing, rather than by using speech, and if the child is mute, the psychiatrist should try offering paper and pencil.
If the child remains violent and out of control and the behaviour is 
being reinforced by attention and anxiety, it will be necessary to ask everyone to withdraw for a while to give the child the chance to calm down on their own. If this still does not help to calm the situation, the psychiatrist will need to set some limits, which could include calling the police to regain control of the behaviour. Medication should only be considered as a last resort when all other strategies to deescalate the situation and calm the child have failed (see Step 5: Management of emergencies in community settings section).

When the child starts to be able to communicate with the 
psychiatrist, they can then be encouraged to give their account of what happened to precipitate the behaviour. As this is explored, it will be possible to assess the child’s mental state (see Chapter 9.1.3) and to form an impression about whether this is mental illness, or whether the disturbed behaviour is the result of emotional turmoil secondary to relationship problems, family conﬂ  ict, or other psy-
chosocial issues. Further information from the parents or carers will be needed to clarify this.
If child abuse is suspected, an interview with the child alone is 
crucial. The psychiatrist will need to enquire about the possibilityof physical and sexual abuse without using leading questions
(3)
(see Chapter 9.3.2). A good starting point is ‘Has anyone ever hurt you or made you do anything you didn’t like?’ The child needs to under-stand that you may need to breach conﬁ  dentiality in order to protect

them from further harm. (see Consent and conﬁ  dentiality section).
Step 3. Interview with parents/carers
It is essential to see the parents or carers as part of the assessment, 
in order to fully understand the context of the crisis, and identify any relevant contributory factors. They may be seen ﬁ  rst, or after 
the child’s assessment, depending on the situation. It is often help-ful to see the parents or carers on their own so that they can speak freely about their child.
These are the areas that will need covering:
◆ History of current episode/disturbance. Current medication?
◆ Previous emotional or behavioural problems.
◆ Brief developmental history: normal or unusual features? Learning difﬁ  culties? School and academic progress.
◆ T emperament; relationships with family/extended family 
members, other adults, peers.◆ Family composition and history (parental separations/divorce; relationships mental and physical illness; recent life events).

During this interview, an assessment can be made of the family 
functioning; the parent’s or carer’s mental health, and their attitude to the child, and whether this seems to be playing a part in the current 
problem (e.g. high levels of family discord; rejecting, neglectful or 
hostile attitudes to the child; harsh parenting practices; parental depression, anxiety, drug or alcohol abuse).
Vignette 3 :
A 10-year-old has been raging around his house for several hours, fol-
lowing an argument with his mother about going out with his friends. He has been smashing toys and kicking in doors and wrecking his bedroom. His single mother and 6-year-old sister are terriﬁ  ed and 
cowering in the sitting room.
The psychiatrist spoke calmly to the boy through the door,

The psychiatrist spoke calmly to the boy through the door, 
stating that he wanted to talk to him. The boy continued being aggressive and abusive and the psychiatrist then said he would give him 5 minutes to calm down and come out, otherwise the police would have to be called in to help. The boy did then manage to calm down and talked about his resentment of his mother’s rules, and his angry feelings about the loss of his father, who had had little contact with him since leaving the family.
His mother told the psychiatrist that she and the boy’s father had 
divorced a year ago, and there had been on-going disputes with her exhusband about money and his erratic contact with the children. Recently she had become depressed, and her son had become increasingly irritable and oppositional at home. She felt unable to control her boy’s temper outbursts.
The mother agreed to see her GP about her depression, try and

The mother agreed to see her GP about her depression, try and 
talk to her ex-husband about seeing the children on a regular basis, and attend the clinic with the children for some family counselling sessions. The boy appeared relieved that his mother was going to seek some help.
Step 4. Making and sharing the diagnostic 
There should now be sufﬁ  cient information available to make a 
diagnostic formulation. This will include the diagnostic category for the disturbed behaviour, the factors which led up to the acute disturbance; the factors which precipitated it, and the risk factors for continuing or recurring problems.
The Three Ps:
Predisposing FactorsPrecipitatingPerpetuating
These factors may be present in the child herself (temperament, 
illness); in the family environment; at school or college; in the child’s wider social environment (friends, neighbours; clubs, etc.); or any combination of these.
Apart from acute intoxication with drugs or alcohol, and deliberate

Apart from acute intoxication with drugs or alcohol, and deliberate 
self-harm, most child and adolescent psychiatric emergencies in the community fall into three categories:
◆ mental illness
◆ acute behavioural disturbance due to family/psychosocial factors
◆ child abuse9.5.8 the management of child and adolescent psychiatric emergencies

SECTION 9  child and adolescent psychiatry 1810
The psychiatrist should share his formulation with the child and 
parents/carers, using age-appropriate, and jargon-free language, to help their understanding of the events. Sometimes the parents or the child will need further discussions before a shared understand-ing between the psychiatrist and the family about the problems can be reached, and an acceptance of the proposed management/care plan by the family.
The formulation should also be shared with any other 
professionals present, as they may be needed to contribute to the immediate management plan, or even to take over the care of the child.
Step 5.  Management of emergencies in 
community settings (see Fig. 9.5.8.1)
Mental illness
The emergency management of a child diagnosed with a mental

The emergency management of a child diagnosed with a mental 
illness will depend on the risk assessment. Is the child a danger to himself or others? If the psychiatrist considers this to be a high risk, then referral to inpatient care will be necessary to allow further assessment and treatment in a safe setting. Compulsory admission, using mental health legislation, may be required if the child or the parents refuse to cooperate with this plan (see Consent section). In some places, it may be possible to admit younger children to a pae-diatric ward for further observation and treatment. Where there are medical complications of a mental illness (for example, low output cardiac failure in severe anorexia nervosa), admission to a paediatric or medical ward will be needed.
If there is a low risk of any danger, and the child and family are

If there is a low risk of any danger, and the child and family are 
cooperative, the psychiatrist can prescribe appropriate medication 
for the mental illness (see Chapter 9.5.5), give advice on the man-agement of the symptoms in the short-term, and arrange for early 
follow-up and review in the outpatient clinic.
Acute behavioural disturbance (no mental illness)
Very often, the situation is defused by the psychiatrist’s assessment, and the child’s behaviour settles. In this case, the psychiatrist will need to decide whether there is a high risk of further episodes. If not, she may simply give advice to the family about how to avoid or deescalate future situations, and inform the child’s GP about the incident. However, if she has identiﬁ  ed signiﬁ  cant ongoing issues 
underpinning or precipitating the child’s disturbed behaviour, she will need to give the family advice about how to try and deal with these. For example, if the child has difﬁ  culties with family conﬂ  ict,

the psychiatrist could recommend referral for outpatient family 
therapy or anger management; if stress at school was linked to the 
outburst, she might advise the parents to arrange a meeting with the child’s teachers; or she could advise a parent to seek help for their own mental health problems (such as depression or addiction) or social problems such as overcrowding or ﬁ  nancial difﬁ  culties.
If the disturbed and violent behaviour continues in spite of the 
psychiatrist’s intervention, a decision must be made about how best to regain control of the situation. The police may need to be 
called in, to provide sufﬁ  cient manpower to safely control the 
violent behaviour. It may be possible to change the environment by calling in signiﬁ  cant other people (for example, another relative) 
who can calm the child. The use of medication needs very careful consideration.

(4) Children may react paradoxically to sedatives and tranquillizers, and the use of medications with the risk of respiratory 
suppression is not recommended unless life support equipment (and staff) is available. However, sometimes it may be possible to persuade a child to accept an appropriate dose of oral medication such as lorazepam or midazolam, and this may be beneﬁ  cial.
(5)
Child abuse
Although it is not common for child abuse to present as a psychiatric

(5)
Although it is not common for child abuse to present as a psychiatric 
emergency, nevertheless it is vitally important for any psychiatrist on call to be able to recognize this, and manage the situation accord-ing to local child protection procedures. If the child is making alle-gations of abuse, these will need to be discussed with the parents/carers, and then it will be necessary to consult with other profes-sional colleagues (including the police, social services, or paediatric staff) to decide on how best to care for the child. The welfare of the child must always be paramount, even if this involves the child being taken to a place of safety such as a paediatric ward or to alter-native accommodation while further investigations are carried out. Clear and accurate notes of all aspects of the assessment are vital as they may be needed for legal proceedings later. (The assessment of possible child abuse is considered further in Chapter 9.3.3.)

Emergencies in paediatric/medical wards
Psychiatric assessment and advice is needed at times for children 
showing acutely disturbed behaviour on paediatric wards, as well as for deliberate self-harm.
The child may be acting bizarrely or aggressively. The psychiatrist 
will need to make a thorough assessment of the situation, including the background of the child and family and the medical aspects of the case. He will then need to assess whether the behaviour is part of the physical illness, (e.g. hypoglycaemia, hypoxia, delirium, pain), a 
primary mental illness (e.g. psychosis, somatoform reaction), the side 
effects of medication, or an acute behavioural reaction. Management will need to be discussed and agreed with the paediatric staff, and shared with the family if they are available. The psychiatric assess-ment and care plan should be carefully written up in the medical ﬁ le to ensure continuity through shift changes of the ward staff.

The use of sedation needs to be given careful consideration, and 
used only if other strategies fail (such as ﬁ  nding out from the child 
the cause of any upset and talking it over; moving the child to a qui-eter setting; calling in the parent to help reassure or pacify the child). 
Oral lorazepam or midazolam are useful drugs of ﬁ  rst choice.
If the primary problem is one of mental illness and the child cannot 
be cared for effectively and safely in a paediatric ward setting, bearing in mind the needs and safety of the other patients, then transfer to a 
psychiatric ward will need to be arranged as soon as possible.
Follow-up visits or phone calls to the ward will be needed, to 
make sure the child is improving or to reconsider the diagnosis 
or treatment.
Psychiatric problems in paediatric or medical wards are con sidered 
further in Chapter 9.3.4
Step 6. Follow-up and communication with 
other professionals
Effective management of the emergency situation can be under mined

Effective management of the emergency situation can be under mined 
by inadequate follow-up arrangements or poor communication between professionals and agencies. It is therefore very important

1811
that the on-call psychiatrist communicates with the child’s general 
practitioner, the team providing routine care for the child, and any other relevant professional involved as soon as practicable, usually the following day. This will hopefully ensure that there is a seamless provision of care for the child and the family, and prevent or fore-stall future emergencies.
Consent and conﬁ  dentiality issues
(a) Consent
Psychiatrists who assess and treat children and adolescents, like all

Psychiatrists who assess and treat children and adolescents, like all 
mental health professionals, have a duty of care to ensure that the welfare of children is protected. They must also work within the limits of the laws of the land. This means that care and attention must be paid to the rights of children to consent to their treatment, while at the same time taking into account the circumstances, their mental capacity, their parents’ views and the risks and necessity for treatment. In many cases, the sharing of information with the child and the family, and their involvement in the decision about the best care will ensure that an agreement can be reached. However, there are other occasions when either the child or their parents refuse to cooperate with treatment felt to be essential by the psychiatrist. If the child is refusing but the parents consent, it is usually possible to treat the child under parental consent, or for adolescents, to use

other legal means (for example, the mental health legislation to 
allow the hospitalization and treatment of a mental disorder). If the child is consenting to treatment, but the parents refuse, care proceedings may need to be considered. If both child and parents are refusing treatment, the situation is very difﬁ  cult and a second 
opinion on the need for treatment and legal advice may have to be obtained before anything further can be done.
(b) Conﬁ  dentiality
The conﬁ  dentiality of the doctor–patient relationship, as men-
tioned in the Hippocratic Oath, is a fundamental prerequisite for patients being able to trust their doctor with sensitive information. However when working with children and adolescents, conﬁ  denti-
ality is complicated by the need to share information with parents, in order for them to fulﬁ  l their responsibilities to their child, and

ality is complicated by the need to share information with parents, in order for them to fulﬁ  l their responsibilities to their child, and 
also with the other agencies which may be involved in providing services for the child (education, social care, etc.). Children and their families should be informed of the scope of any promises of conﬁ  dentiality at the beginning, and it is always good to ask for 
the child’s or adolescents’ consent to share information where this is necessary and in the best interests of the child. Breaches of conﬁ  dentiality may be clinically or legally necessary (such as where 
an adolescent with a mental illness is exposing them self to risk, or 
when child abuse is suspected).
Tan et al.
(6) provide a full discussion of these issues, and decision-

Tan et al.
making algorithms. Effective management of an emergency should result in the child receiving appropriate care and treatment, the parents having a greater understanding of the issues associated with the disturbed behaviour, and any other professionals feeling supported by the psychiatrist’s advice and intervention. This will all reduce the likelihood of further emergency situations arising for that child and family.
Jones, D.P .H. (2003). Communicating with vulnerable children . Gaskell, 
London.References
 1. Halamandaris, P .V . and Anderson, T.R. (1999). Children and 
adolescents in the psychiatric emergency setting. The Psychiatric Clinics 
of North America ,22(4), 865–74.
 2. Stewart, C., Spicer, M., and Babl, F. (2006). Caring for adolescents with

 2. Stewart, C., Spicer, M., and Babl, F. (2006). Caring for adolescents with 
mental health problems: challenges in the emergency department. Journal of Paediatrics and Child Health ,42(11), 726–30. DOI: 10.1111/
j.1440-1754.2006.00959.x
 3. Jones, D.P .H. (2003). Communicating with vulnerable children . Gaskell, 
London.
 4. Sorrentino, A. (2004). Chemical restraints for the agitated, violent or 
psychotic paediatric patient in the emergency room; controversies and 
recommendations. Current Opinion in Pediatrics, 16,201–4.
 5. Taylor, D., Paton, C., and Kerwin, R. (eds.) (2007). Rapid 
tranquillisation (RT) in children and adolescents. In The Maudsley 
2005–2006 prescribing guidelines 8E, p. 226. Taylor and Francis Group, 
London and New Y ork.
 6. Tan, J.A.O., Passerini, G., and Stewart, A. (2007). Consent and

 6. Tan, J.A.O., Passerini, G., and Stewart, A. (2007). Consent and 
conﬁ  dentiality in clinical work with young people. Clinical Child 
Psychology and Psychiatry ,12(2), 191–210. 
DOI: 10.1177/1359104507075921.
9.5.9 The child psychiatrist as 
consultant to schools and colleges
Those who provide public services for children and young people 
may have a role in the identiﬁ  cation, prevention, and within rea-
sonable parameters, the treatment of mental health problems. Social services and education in particular have a key responsibility to safeguard the physical and psychological health of children and identify potential areas of avoidable harm, including those which may develop within their institutions.
There is a well-recognized mismatch between the rates of child 
mental health problems identiﬁ  ed in epidemiological studies and

mental health problems identiﬁ  ed in epidemiological studies and 
the number of children referred to child and adolescent mental health services (CAMHS). School staff will often be in the best position to identify unrecognized difﬁ  culties and also to help chil-
dren and their families address prejudices associated with referral to CAMHS, though they may need training and help to do so.
The responsibilities of teachers have been conﬁ  rmed by schools’ 
inclusion within the broad concept of CAMHS in a number of countries. In the United Kingdom, the Health Advisory Service (now the Health and Social Care Advisory Service—HASCAS), proposed a model, subsequently adopted by the Department of Health of a tiered approach to service provision, in which schools, alongside primary medical care and social services formed the ﬁ  rst 
Tier.
(1) Within this model schools have been seen as offering unique

Tier.
(1) Within this model schools have been seen as offering unique 
opportunities to identify problems, provide simple assessments and refer up to more specialized tiers as judged appropriate and in negotiation with caregivers. T eachers though, often feel inade-quately trained to fulﬁ  l this role and look to other professionals, 
including psychiatrists to advise and support them. Fortunately there are a number of professional roles, some employed within 9.5.9 the child psychiatrist as consultant to schools and colleges

SECTION 9  child and adolescent psychiatry 1812
education and some outside, forming a bridge between education 
and mental health services. Some of these roles vary in their detail between countries, but most developed countries will have profes-sionals (possibly with different titles) ﬁ  lling roles comparable to 
those in the United Kingdom.
It is important to note that CAMHS generally work as multi-
disciplinary teams, hence any support and liaison may be offered by a range of professionals and not exclusively by psychiatry. One of the HAS recommendations was the creation of a new professional group—the primary child mental health worker—with the particular aim of liaising between Tier 1 and Tier 2 ser-vices. The following are some of the professionals involved in the interface between child mental health and education:
Primary child mental health worker
A practitioner, often with a mental health nursing background, employed either by education or CAMHS with the speciﬁ  c brief to

A practitioner, often with a mental health nursing background, employed either by education or CAMHS with the speciﬁ  c brief to 
liaise between the two in identifying children with mental health needs.
Special educational needs coordinator (SENCO)
Employed by the school as a teacher, the role of the SENCO is primarily to develop effective ways of identifying and removing barriers to learning, which may result from intellectual retardation, physical, or mental health problems. Alongside primary child mental health workers they have a role in the identification, management, and referral of children as well as a responsibility to contribute to in-service training for teachers.
Educational psychologist

Educational psychologists (EP) provide assessments of special educational needs. In the United Kingdom a consultation model has been adopted, whereby the Educational Psychologist meets with the person who has raised concerns as they are likely to be the person most motivated to bring about change. The new model recognizes that teachers are often skilled in assessing pupil attain-ment, learning styles, behaviour, strengths, and weaknesses. EPs have an important role in early identiﬁ  cation and intervention and 
aim to promote child development and learning through the appli-cation of psychological theory using information gathered within a wider ranging context.
Education welfare ofﬁ  cer (EWO)
In the United Kingdom, each school has an EWO assigned, to

In the United Kingdom, each school has an EWO assigned, to 
provide a support service to families and schools to help them meet legal obligations related to a child’s education. They work with parents/carers to monitor attendance, with schools to consider courses of action of beneﬁ  t to poor school attendees and 
with other agencies (e.g. health, social services, police, and youth offending teams) to provide a suitable programme that will help the child return to full-time education.
School nurse
An integral part of the school health team, the school nurse’s responsibilities include supporting children with complex health needs, running immunization programmes, providing drop-in clinics, parenting programmes and bed-wetting clinics, assessing the health needs of every child on starting school, and providing health schemes for young people.Learning mentor

Learning mentors have a broad remit including supporting the safe and effective transition from primary to secondary school, supporting provision for pupils with special educational needs and developing a relationship with identiﬁ  ed pupils, based on a 
trusting individual relationship.
Connexions advisors
Primarily concerned with those in the 13–16 age range, connexions advisors offer one-to-one support and guidance similar to that pre-viously carried out by careers ofﬁ  cers. There is a strong emphasis 
on surveillance and monitoring. Y oung people who are seen to be ‘at risk’ of dropping out of education or who present behavioural problems are a priority for intervention. Personal advisers act as advocates, especially for those who are vulnerable or who have 
special needs.
Teachers’ training in mental health
Despite their responsibility for identifying mental health problems, teachers in many countries are offered little speciﬁ  c training in this

Despite their responsibility for identifying mental health problems, teachers in many countries are offered little speciﬁ  c training in this 
area. In the United Kingdom, most post graduate certiﬁ  cate of 
education courses offer only a very small amount of time, perhaps as little as a half day to the teaching of special educational needs. A survey of SENCO’S training and their wish for further teaching about mental health issues
(2) revealed a signiﬁ  cant lack of training. 
Many had no training in 3 years. In contrast they showed a great willingness to receive more and welcomed liaison from CAMHS professionals. There have been a number of useful initiatives to improve teachers’ experience including the National Healthy Schools Programme
(3) which aimed to improve learning by reduc-

ing emotional and health inequalities using a whole school approach; this involved improving the emotional literacy not only of pupils but of staff and parents too.
Developing a school liaison service
Establishing a liaison service between CAMHS and a school can have a number of beneﬁ  ts including:
◆ Early identiﬁ  cation of child mental health problems
◆ Information sharing
◆ Monitoring and evaluation of treatment e.g. for attention-deﬁ  cit 
hyperactivity disorder (ADHD)
◆ Establishing pathways of referral to higher tiers of service
◆ Offering school-based interventions for common problems
◆ Promoting the development of social skills and positive self-esteem.
The majority of CAMHS services do work with schools, the

The majority of CAMHS services do work with schools, the 
nature of the intervention ranging from consultation and support for school staff to direct work with children, including observation and assessment. However, joint working between CAMHS and schools has a record of patchiness across the United Kingdom, with a lack of key personnel often leading to a fragmented service.
Good examples of joint practice are characterized by second-
ments between organizations, shared working environments, a clear understanding of the different roles and expertise of team members, and a shared vision of joint working.

1813
Where good practice is operating, schools are often faced with 
anxieties around short-term funding for speciﬁ  c projects, for 
example, the recent initiatives ‘City Education Action Zones’ , ‘Health Action Zones’ , and the ‘Healthy Schools Standards’ .
Schools in the United States tend to operate within multi-
disciplinary settings and research suggests that these are effective in breaking down professional barriers and also addressing the stigma associated with a young person being referred to external agencies such as CAMHS.
The provision of a key mental health worker within the school 
facilitates better communication between services and helps develop a greater understanding of how the culture of a school operates. Integrated links between CAMHS and the local authority, educational psychologists, behaviour and emotional support teams, and education welfare promotes a cohesive and collaborative service for children.
Practical issues

In order for a CAMHS service to establish an effective working link with a school, there are several issues to address:
(a) Gaining the cooperation of all the staff
Commitment of all staff (and indeed parents) rather than just one interested teacher is crucial. Effective prevention, treatment, and referral pathways require a ‘whole school’ approach.
(b) Negotiating realistic aims
Child mental health problems are common and often long-lasting; a realistic balance should be struck between prevention and management.
(c) Establishing a level of service
Both the school and CAMHS should be clear about who is pro-viding the service, at what frequency and the expected level of commitment on both sides. There should be perceived beneﬁ  ts 
to the school and CAMHS. Does the service provide an urgent referral component or not? Who is the named contact?
(d) Conﬁ  dentiality
Schools say that policies around sharing information act as barriers

Schools say that policies around sharing information act as barriers 
to effective joint working and so there is a need to determine a process whereby a joint strategy on conﬁ  dentiality is agreed. At an 
individual level, young people can expect that private discussions on personal matters should be kept conﬁ  dential unless they are 
told otherwise. However, teaching staff should not give unreserved assurances on conﬁ  dentiality as these may have to be breached

told otherwise. However, teaching staff should not give unreserved assurances on conﬁ  dentiality as these may have to be breached 
if the young person discloses information which leads an adult to believe that they or others are at risk. Sometimes the teacher will need to share information with others in the staff team in the young person’s interests, or for supervision purposes. On occasions, (for example, where there is a serious risk of self-harm) it will be neces-sary to contact parents, but in these circumstances the young person should be told explicitly what has been shared with whom and why. Conﬁ  dences should not be breached to other pupils.
(e) Pitfalls
There are several dangers of providing a mentoring/counselling 
service for the inexperienced teacher. Some of the commonest are: becoming over involved (emotionally and with time), giving unconditional guarantees of conﬁ  dentiality, and dealing inappro-

priately with pupils concerns about another pupil. Obtaining advice or supervision from a more experienced member of the 
team or a CAMHS liaison worker is the most effective way of addressing these difﬁ  culties.
What do teachers need to know?
(a) Education about mental health problems
Surveys suggest teachers want to understand the common presen-
tations of mental health problems in childhood, how they affect children’s behaviour, and their impact on learning. They are often uncertain about aetiology and prognosis. Where disorders have a genetic component to their aetiology, teachers often mistakenly believe that this diminishes the potential impact of school-based interventions. They like to understand the distinction between generalized and speciﬁ  c learning difﬁ  culties.

Distinguishing disorder from bad behaviour is especially 
complex, particularly when attempting to differentiate between what a child can’t or won’t do. This is commonly an issue with hyperactive children whose attention in school is poor.
(b) Identiﬁ  cation/detection
T eachers beneﬁ  t from guidance on the detection of disorders, by 
learning about common symptoms and behavioural phenotypes. They can be helped in this by being aware of groups at risk and by the use of screening instruments designed to be used in school. Commonly used measures include the Conners T eacher Rating scale (CTRS)
(4) and the Strengths and difﬁ  culties quest ionnaires.(5)
(c) Interventions/treatments teachers can deliver in school
These may include simple counselling interventions, e.g. to address

These may include simple counselling interventions, e.g. to address 
anxiety at exam times or supporting a child during parental sepa-ration or after a bereavement. The teacher’s role may involve sup-porting the administration of medication within school (e.g. for hyperactivity). This treatment (and the child’s motivation to take it) can be severely undermined if teachers do not support its use.
(d) Knowledge/understanding of treatments given by CAMHS
Many myths about child mental health problems and their treat-ment may be shared by teaching staff. These include the aims, ben-eﬁ ts, and likely adverse effects of medication. Some will mistakenly 
believe, for example that drugs for hyperactivity are sedative and will turn a child into a ‘zombie’ . Stigmatizing attitudes to inpatient child psychiatry units may impair a child’s rehabilitation after admission.

(e) Pathways of referral
Schools should be clear about which problems should be referred to which agency. For example, acute self-harm should be referred to the accident and emergency department of a general hospital, whilst child protection issues should be referred to social services.
Speciﬁ  c issues posing a challenge for schools
A major concern for a school is how to manage disruptive disorders 
and their impact on other children. A disorder such as T ourette’s syndrome will excite younger children and they will be easily distracted. Those whose attention is poor, who are more impulsive or who are low achievers are particularly vulnerable, whilst the subject may ﬁ  nd their behaviour reinforced by their unexpected 
celebrity and status as the ‘class clown’ .
Appropriate behavioural management can be difﬁ  cult to institute 
without it being punitive or unwittingly reinforcing. This applies to 9.5.9 the child psychiatrist as consultant to schools and colleges

SECTION 9  child and adolescent psychiatry 1814
conduct problems and for example where teaching staff may offer 
lunchtime supervision of a child with an eating disorder.
It is often difﬁ  cult to address minor self-harm sympathetically 
without reinforcing the behaviour. Similarly the wish to be sympa-thetic towards those with eating disorders may be tempered by concerns to avoid ‘epidemic’ dieting.
The school’s role in child protection
Schools in the United Kingdom have a responsibility to safeguard and promote the well-being of pupils under the Education Act of 2002
(6) and, where appropriate, under the Children Act 1989.(7)
Each school has a designated lead for child protection and if staff have concerns about the safety and well-being of a child they should report their concerns to them. The child protection lead will refer to the school Child Protection Policy and then directly to Children’s Social Care services as necessary.

A guidance document ‘safeguarding children and safer recruit-
ment in education ’ was produced in the United Kingdom in 2006
(8)
and is a consolidated version of earlier guidance material. It focuses 
on the recruitment and selection processes, vetting checks, and duties for safeguarding and promoting the welfare of children in education. The document also forms a guide to inter-agency working. The guidance explains that a school should ‘create and maintain a safe learning environment’ and have the appropriate arrangements in place. Child protection arrangements, pupil health and safety, and bullying are all subject to statutory requirements. The guidance directs that if a child is the subject of an inter-agency child protection plan, the school should be involved with the prep-aration of that plan.
Through the delivery of personal, health, and social education 
(PHSE) the school may provide opportunities for children and y oung

people to learn about keeping safe. Pupils should be taught to:
◆ Recognize and manage risk in different situations and then 
decide how to behave responsibly
◆ Judge what kind of physical contact is acceptable and unacceptable
◆ Recognize when pressure from others (including people they know) threatens their personal safety and well-being and develop effective ways of resisting pressure.
School-based intervention strategies

A healthy school promotes physical and emotional health by pro-viding accessible and relevant information and equipping pupils with the skills and attitudes to make informed decisions about their health. It understands the importance of investing in health to assist in raising levels of pupil achievement and improving stan-dards. It also recognizes the need to provide both a physical and social environment that is conducive to learning.
The National Healthy School Standard was part of the Healthy 
Schools programme, led by the DFES and the Department of Health.
(9) Launched in October 1999, it offered support for local

(9) Launched in October 1999, it offered support for local 
programme coordinators and provided an accreditation process for education and health partnerships. It provided a model of partnership working between the health service and schools, with the aim of promoting a coherent and holistic message about the importance of a healthy lifestyle.The standard covered four key themes:
◆ Personal, Health, and Social Education (PHSE).
◆ Healthy eating
◆ Physical activity
◆ Emotional health and well-being (including bullying)
PHSE is now included in many countries’ teaching curricula.

PHSE is now included in many countries’ teaching curricula. 
This provides education on social and emotional development and citizenship, including the individual’s place in society, responsibil-ity, and rights. In The United Kingdom, the PHSE syllabus now has sessions on mental health issues including the use of drugs and alcohol and the links between drug misuse and mental illness. It also covers self-harm and suicidal behaviour.
Social and Emotional Aspects of Learning—(SEAL)  is a whole-
curriculum framework for teaching social, emotional, and behav-ioural skills to primary school children in ﬁ  ve areas: self-awareness, 
managing feelings, motivation, empathy, and social skills. In 2004, the scheme was piloted in 250 schools in 25 authorities in the United Kingdom with a subsequent planned extension to high schools.
Secondary prevention

Solution Oriented Schools (SOS)  is an approach used in many 
United Kingdom local authorities, comprising training and resources to support the whole-school promotion of positive behaviour. The focus is on establishing small steps that can be taken to resolve conduct problems, attendance issues, poor peer group interactions and negative attitudes to learning.
The approach invites staff to consider: ‘What works in school?’ . 
It encourages them to take a pragmatic approach; learning from what is working, leaving behind practice that is failing to pay-off, recognizing ‘the problem’ as the problem (not the child, teacher, or professional), and building on strengths that each individual brings. It stems from the principles of solution-oriented brief therapy which focuses on ﬁ  nding and creating solutions to a problem whilst 
spending little time on the problem itself.
Circle time  was developed in the 1930s particularly for primary

Circle time  was developed in the 1930s particularly for primary 
schools, as a forum for children to share views and concerns about 
issues arising in school (such as bullying) or outside (within the family or neighbourhood). It is still widely practised.
Mobile phone, text, and Internet-based initiatives
A number of education authorities have developed pilot schemes using new technologies such as online counselling and support services. Various websites offer qualiﬁ  ed counsellors and other 
support services. Services are conﬁ  dential and young people book 
in for their session of online chat. In addition the young people can often access a Frequently Asked Questions area. Some sites have counsellors who can make referrals to CAMHS for the young people who access them.
Other initiatives include a pilot scheme in Wales in which pupils

Other initiatives include a pilot scheme in Wales in which pupils 
used mobile phones to text their school nurses for health advice. This short-term project ran in office hours, offered students instant help and provided those who might be wary of approach-
ing adults with their problems face-to-face the chance to do so 
anonymously.
In Liverpool, The Health and Education for Life Project (HELP)
was set-up in 2003, as an action research project that worked in

1815
schools to change pupils’ attitudes towards mental health issues 
and to provide coping strategies.
Meeting the needs of children with special 
educational needs
While most pupils with complex needs are educated in special 
schools, where the special needs of children can be met by a main-stream school, they are often taught in this setting. Attitudes to inclusion have changed over time. The latest draft guidance in the United Kingdom moves away from the inclusion drive of 2004 and advises councils that they should provide a ‘range of provision’ for children with special educational needs. The national curriculum requirements may often impact negatively on the experiences of a young person with speciﬁ  c learning needs; the challenge for

teachers is to create a stimulating, engaging programme of study whilst still meeting the national requirements. The use of teaching assistants in a creative and well-planned way can facilitate the deliv-ery of lessons in an inclusive setting. Ultimately, the needs of the 
individual child should be of primary concern in the inclusive–
exclusive decision-making process.
Some special schools offer outreach to the mainstream, so that 
expertise can be shared and support given for inclusive practice. Some local authorities name specialist schools for each area to meet the needs for example, of autistic young people. Where a young person lives too far from the locality of the specialist school; the specialist school may adopt an advisory role.
Special schools attempt to offer a tailored and focussed response 
to the needs of speciﬁ  c groups of young people; it is arguable that a

to the needs of speciﬁ  c groups of young people; it is arguable that a 
young person who has for example, high functioning Asperger’s syndrome will feel more ‘included’ in a special school setting where his differences are less noticeable. The social exclusion that such a young person may experience in a mainstream setting can have detrimental effects on their progress. Successful inclusive educa-tion relies on a school approach that creates an inclusive culture; develops inclusive policies, and evolves inclusive practices.
Children and young people with emotional and behavioural 
difﬁ culties (EBD) present a major challenge to schools attempting 
to become fully inclusive organizations. Through emotional literacy programmes such as SEAL, anger management groups, social skills, and self-esteem groups, schools can offer a variety of behavioural interventions that support an inclusive experience.

Hospital schools or Medical Pupil Referral Units  offer education to 
young people who are unable to attend school because of medical needs. The term ‘medical needs’ includes those with mental illness; anxiety, depression, and school phobia. There is a strong emphasis on a strategic planning framework which ensures a continuum of 
provision; a focus on close liaison with all parties and the develop-
ment of a robust reintegration plan.
The role of CAMHS within special education has a higher proﬁ  le

The role of CAMHS within special education has a higher proﬁ  le 
than in many mainstream educational provisions; children should all have statements of special educational need and therefore should be reviewed regularly. The reviews of children with a statement of emotional and social need or with autistic spectrum disorders (ASD) tend to require the involvement of a CAMHS worker; sub-sequently good relationships are developed through close and regular interactions with educationalists. CAMHS may offer con-sultation and advice or direct intervention with the child or group of children in a special educational setting.The psychiatrist as advisor to 
higher/further education
Recent years have shown a growing awareness of the unmet needs 
of students in higher education.(10) Although higher education

of students in higher education.(10) Although higher education 
institutions often have quite sophisticated pastoral and counselling provision in place, they may need to consult with mental health services regarding issues with speciﬁ  c students. The psychiatrist 
should be aware of the following particular issues in relation to this group:
◆ The vulnerability of young people living away from home for the ﬁ  rst time.
◆ Recent expansions in student numbers. In a number of coun-
tries, greater training opportunities for young people have resulted in access to higher education no longer being restricted to those from privileged backgrounds. One adverse consequence of this otherwise desirable state of affairs is that those with greater risks (or indeed histories) of mental health problems may take up places at colleges and universities.

◆ Vocational courses. Some courses (such as medicine, nursing, and social work) may restrict those suffering with particular mental health problems. The psychiatrist may have a duty to report such issues as, for example, drug dependence. Related to this a student may be reluctant to disclose a problem which would have implications for continuing on their course.
◆ Interface/communication issues. Y oung people living away from home at college may be vulnerable to falling into any gap that might exist between child and adult services and between services local to their home and those at their college. Effective communication between service providers is of paramount importance.
◆ Conﬁ  dentiality. Students are often concerned about conﬁ  dentiality 
from their parents, their peers, and their college’s academic staff. As with the examples given earlier in this chapter, conﬁ  dences 
should only be breached on a strictly ‘need to know’ basis.

As participation in education is almost universally compulsory for children, schools are in a unique position to offer prevention and identiﬁ  cation of child mental health problems. Effective prac-
tice requires good liaison with CAMHS. There are a number of obstacles to effective working but recent times have seen a number of examples of good practice and policies to support these.
Royal College of Psychiatrists. (2003). Mental health of students in higher 
education. Council report CR112 . Royal College of Psychiatrists, 
London.
The National Healthy Schools Programme. www.healthyschools.gov.uk
Safeguarding Children. www.everychildmatters.gov.uk
 1. Health Advisory Service. (1995). Together we stand: the commissioning, 
role and management of child and adolescent mental health services .
HMSO, London.9.5.9 the child psychiatrist as consultant to schools and colleges

SECTION 9  child and adolescent psychiatry 1816
 2. Gowers, S.G., Thomas, S., and Deeley, S.D. (2004). Can primary schools 
provide effective Tier 1 child mental health services? Journal of Clinical 
Child Psychology and Psychiatry ,9(3), 419–25.
 3. The National Healthy Schools Programme. www.healthyschools.gov.uk
 4. Conners, C.K. (1973). Rating scales for use in drug studies 
with children [Special issue/Pharmacotherapy of Children]. Psychopharmacology Bulletin ,9, 24–9.
 5. Goodman, R. (2001). Psychometric properties of the strengths and 
difﬁ culties questionnaire (SDQ). Journal of the American Academy of 
Child and Adolescent Psychiatry ,40, 1337–45. 6. Department for Education. (2002). Education Act . HMSO, London.
 7. Department of Health. (1991). Children Act 1989; guidance and 
regulations . Department of Health, London.
 8. Safeguarding Children. www.everychildmatters.gov.uk
 9. National Healthy Schools Standard. http://www.standards.dfes.gov.uk

10. Royal College of Psychiatrists. (2003). The mental health of students in 
higher education. Council report CR112 . Royal College of Psychiatrists, 
London.

10.1  Classiﬁ  cation, diagnosis, psychiatric 
1825
1830
David M. Clarke and Shoumitro Deb
 10.5  Psychiatric and behaviour disorders among mentally retarded people  
1849
1849
1854
Anton Došen 10.5.3 Epilepsy and epilepsy-related behaviour disorders among people with intellectual disability  
1860
 10.7  Special needs of adolescents and elderly

1860
1883
1887
Nick Bouras and Geraldine HoltSECTION 10
Intellectual Disability 

10.1
The general principles developed during the latter part of the twen-
tieth century and continued into the twenty-ﬁ  rst century guiding 
support for people with intellectual disabilities remain those of social inclusion and the provision of services to enable people to make, as far is possible, their own choices and to participate as full citizens in society. These are articulated in national policy docu-ments, such as the White Paper for England, ‘Valuing people
(1) and 
also at an international level in the UN Declaration on the rights of people with disability.
(2) However, given that people with intellec-

(1) and 
tual disabilities represent a highly complex and heterogenous group with very varied needs, in order for such objectives to be achieved, a range of community based support and interagency and inter-disciplinary collaboration is required. It is acknowledged that people with intellectual disabilities experience considerable health inequalities with the presence of additional disabilities due to the presence of physical and sensory impairments and co-morbid physical and mental ill-health, much of which goes unrecognized, and also the occurrence of behaviours that impact on their lives and the lives of those supporting them.
(3,4,5)  In the twenty-ﬁ  rst

(3,4,5)  In the twenty-ﬁ  rst 
century, few would now challenge the objectives of social inclusion and community support. The tasks for Government and society are to provide special educational support in childhood and also sup-port to the families of children with intellectual disabilities, and the necessary range of services to meet the social and health needs of this diverse group of people in their adult life. This includes ena-bling adults with intellectual disabilities to gain meaningful sup-port or full employment and to exercise their rights as citizens and to participate fully in society. T o achieve such objectives there is a need to be able to characterize the nature and level of need, to establish the presence and signiﬁ  cance of co-morbid illnesses and/
or challenging behaviours, and to organize and provide support and services to meet such identiﬁ  ed needs.
This complexity of need has meant that no single ‘label’ , such as

This complexity of need has meant that no single ‘label’ , such as 
‘intellectual disability’ , can adequately describe this group of people. What individuals have in common is a difﬁ  culty in the acquisition 
of basic living, educational, and social skills that is apparent early in life, together with evidence of a signiﬁ  cant intellectual impairment. 
However, for some this may be of such severity that, for example, meaningful language is never acquired and there are very substan-tial care needs. For others, there is the presence of subtle signs of early developmental delay, and evidence of learning difﬁ  culties that 
only becomes clearly apparent at school when there is an expecta-tion that more sophisticated skills will be acquired. The nature and

only becomes clearly apparent at school when there is an expecta-tion that more sophisticated skills will be acquired. The nature and 
extent of disability and of any functional impairments in general, distinguishing those people with intellectual disabilities from those with speciﬁ  c learning difﬁ  culties, such as dyslexia.
In infancy and early childhood, the reason for any apparent 
developmental delay needs to be established. This is primarily the responsibility of paediatric and clinical genetic services. Such infor-mation helps parents understand the reasons for their child’s difﬁ culties and may guide, in a limited way, an understanding of 
future needs and potential risks. Later in childhood, the nature and extent of a child’s learning difﬁ  culties and a statement of special

future needs and potential risks. Later in childhood, the nature and extent of a child’s learning difﬁ  culties and a statement of special 
educational needs is the main task and later still, the main focus may be the assessment of longer-term social care needs. Throughout life, there may also be questions about a child’s or adult’s behaviour or mental state or the nature and extent of physical or sensory impairments and disabilities. The role of assessment is essentially to determine need and to inform the types of intervention and treatments, whether educational, medical, psychological, or social, which are likely to be effective and of beneﬁ  t to the person concerned. 
Systems of classification provide useful frameworks for such assessments.
The term ‘classiﬁ  cation’ is unfortunate as it carries with it the stigma 
associated with previous legislation (e.g. Mental Deﬁ  ciency Act, 1913)

associated with previous legislation (e.g. Mental Deﬁ  ciency Act, 1913) 
and the associated history of institutionalization consequent upon the eugenics movement at the beginning of the twentieth century. Classiﬁ  cation, diagnosis, 
psychiatric assessment, and needs assessment

SECTION 10  intellectual disability (mental retardation) 1820
However, systems of classiﬁ  cation are an important way of organ-
izing information and thereby enabling the reliable passing of that information to others and providing a framework to guide inter-vention. Whilst there are clear strengths to this process, any system of classiﬁ  cation has serious limitations. It will tend to focus on a 
few particular characteristics to the potential exclusion of others, and none can impart a truly comprehensive picture. Methods of classiﬁ  cation have inevitably changed over time in an 
attempt to better clarify the key issues and to minimize stigma that 
might be associated with any given label. However, the central 
principle of any system of classiﬁ  cation is to bring order to knowl-

edge in a manner that may then enable further advances or the instigation of interventions that previous research has shown to be effective. There is no single universal system—the system of classi-ﬁ cation used depends on the reasons for its use. These may be as 
diverse as being predominately administrative or for the purposes of guiding intervention and the use or not of speciﬁ  c treatments.
Classiﬁ  cation systems also differ with respect to whether they are 
dimensional or categorical in nature. Intellectual disability illus-trates this difference in that measures such as those obtained from IQ tests are clearly dimensional and continuous whereas labels such as ‘intellectual disability’ or the identiﬁ  cation of particular

syndromes are categorical. More recently such obvious categorical distinctions have begun to break down as the genetic basis for syndromes are more clearly elucidated. For example, in fragile X syndrome there is variation in the extent of the number of repeat sequences in the FMR-1 mutation, both within carrier and affected individuals that inﬂ  uence whether or not an intellectual disability 
is likely to be present.
(6) Various different systems of classiﬁ  cation 
are examined below and the relationship between assessment and classiﬁ  cation is considered.
Mental retardation (DSM-IV)
From January 1st 2007, the previously named American Association 
on Mental Retardation changed its name, replacing ‘mental retar-dation’ with the term ‘intellectual and developmental disabilities’ . This followed similar changes in other organizations. However, in DSM-IV
(7) the term ‘mental retardation’ remains for the moment.

(7) the term ‘mental retardation’ remains for the moment. 
This standard diagnostic system provides a framework for multiax-ial diagnosis with Axis II for personality disorders and mental retardation. Table 10.1.1 summarizes the DSM-IV criteria for men-tal retardation. The focus is not primarily one of aetiology but rather of quantifying the extent of ‘mental retardation’ through deﬁ ning the level of intellectual impairment and listing the range of 
possible adaptive functions that might be impaired. The deﬁ  nition 
makes explicit that the onset is in the developmental period and that mental retardation is the ﬁ  nal common pathway of a number 
of potential aetiologies. Signiﬁ  cant sub-average intellectual func-
tion is deﬁ  ned as an IQ of 70 or below (using standard IQ tests). 
The IQ is also used to help determine the level of mental retarda-tion (mild, moderate, severe, or profound).
The use of such a multi-axial system recognizes the fact that

The use of such a multi-axial system recognizes the fact that 
intellectual disability is a disorder of development, which is sepa-
rate from other mental disorders, such as mental illness (Axis I), 
general medical conditions (Axis III), and which may be associated with particular psychosocial and environmental problems (Axis IV). Thus, the process of formulation requires that all these broad domains be considered in arriving at an understanding of an individual’s particular difﬁ  culties.International Classiﬁ  cation of Functioning, Disability 
and Health (ICF)
In 2001, the World Health Organization published the International 
Classiﬁ  cation of Functioning, Disabilities and Health (ICF).(8) This 
is a complete revision of the International Classification of Impairments, Disabilities, and Handicaps.
(9) The latter classiﬁ  ca-

tion was an advance at that time in that it had attempted to overcome the limitations of other methods of classification (particularly with respect to chronic disability) and, most impor-tantly, aimed to guide intervention at several levels and in a more holistic manner than classiﬁ  cation systems that were primarily

focused on diagnosis, had been able to do. In this context, intellec-tual disabilities could be conceptualized at different levels. In the case of impairment, the organ system involved is that of the central nervous system. It is the impairment of this system for genetic, chromosomal, or environmental reasons that have primarily affected the acquisition of developmentally determined skills and the ability to learn. The associated disability is the effect of the impairment on a person’s ability to learn and acquire new skills that come with development. The exact nature and extent of the disability may not only include the impact of an intellectual disability but also physical and sensory disabilities. The extent to which a given 
Table 10.1.1  Summary of the diagnostic criteria for mental 
retardation (DSM-IV)
A. Signiﬁ  cant subaverage general intelligence
B.  Signiﬁ  cant limitations in adaptive functioning in at least two of the 
 Communication Self-care
 Home living

 Social/interpersonal skills Use of community resources
 Self-direction
 Functional academic skills
 Work
 Leisure Health
 Safety
C. Onset before age 18 years of age
Note
◆  Signiﬁ  cant subaverage intellectual functioning is deﬁ  ned as an IQ of about 
70 or below. The choice of testing instrument should take into account 
the individual’s socio-economic backgr ound, native language, and other 
associated handicaps
◆  Adaptive functioning refers to how effectively individuals cope with 
common life demands and how well they meet the standards of personal 
independence expected of someone in their particular age group, 
sociocultural background, and community setting. Adaptive behaviour may be inﬂ  uenced by individual and/or environmental factors including

sociocultural background, and community setting. Adaptive behaviour may be inﬂ  uenced by individual and/or environmental factors including 
the presence or not of additional mental or physical disorders. Information 
on adaptive behaviour should be gathered from one or more independent sources
◆  The degree of severity of mental retardation may be speciﬁ  ed on the basis 
of intellectual impairment taking into account other aspects of functioning
  Mild mental retardation: IQ level 50–55 to approximately 70
  Moderate mental retardation: IQ level 35–40 to 50–55  Severe mental retardation: IQ level 20–25 to 35–40  Profound mental retardation: IQ level below 20 or 25

1821
impairment results in a loss of function (disability) may well be 
inﬂ uenced by the extent and nature of interventions such as special 
education, or the correction of hearing loss through the use of a hearing aid. The ﬁ  nal level, that of ‘handicap’ , is a consequence of 
an interaction between the disability and the extent to which support is available or environmental adjustments made. It is a measure of disadvantage that can be ameliorated through, for example, the presence of carers to enable individuals to go out, or environmental modiﬁ  cations (e.g. wheelchair ramps) that diminish 
the impact of physical disabilities.
The ICF attempts to take classiﬁ  cation further and to conceptu-

alize ‘disability’ within the context of society as a whole, recogniz-ing that everyone can experience disability at one time or other—the stated aim of the ICF is to ‘mainstream the experience of disability and recognize it as a universal human experience’ . The intent is to encourage those using the ICF to take into account more fully the social aspects of dysfunction and not to see disability as only a medical or biologically determined dysfunction. This means of classiﬁ  cation aims to enable the recording of the environ-

mental effects on an individual’s functioning. The ICF itself is divided into two Parts. Part 1 is concerned with ‘Functioning and Disability’ and Part 2 is concerned with ‘Contextual Factors’ . Each of the two components are expressed in both positive and negative terms in order to emphasize what a person is able to do as well as what he/she is not able to do. The ICF is more complex and more comprehensive than the 1980 WHO system of classification attempting to provide a conceptual framework that forces a much wider understanding by bringing together more comprehensively social and biological models of disability. In doing so, it does what a sound formulation should do, moving from the limitations of a diagnosis to an understanding of the individual within a biological, social and environmental context. This is illustrated in the diagram in Fig. 10.1.1 taken from the ICF.
As with the 1980 ‘Impairments, Disabilities and Handicaps’

As with the 1980 ‘Impairments, Disabilities and Handicaps’ 
means of classiﬁ  cation, the ICF is seen as complementing other 
WHO classiﬁ  cation systems, such as the ICD-10.
(10) The ICD-10 is 
focused on disease and the ICF on ‘components of health’ . The latter, in doing so, provides an appropriate means for characteriz-ing need and for ensuring that people with chronic disabilities have such needs met in the context of their individual human rights and also based on rights established through national legislation. However, as knowledge has increased, for example, about the nature and extent of physical and psychiatric co-morbidity affect-ing people with intellectual disabilities, so then has the need to use different and other relevant systems of classiﬁ  cation increased. Such different approaches provide the necessary frameworks for a 
rigorous and comprehensive formulation of a person’s needs and to guide treatment of any identiﬁ  ed co-morbid illness.

Assessment is a task that is undertaken to address speciﬁ  c questions 
and is informed by the relevant theoretical knowledge and concep-tual framework. The type of assessment undertaken therefore, depends on the issue in question and in turn, on both the relevant theoretical background and the appropriate systems of classiﬁ  ca-
tion, where they are required. The above systems of classiﬁ  cation 
provide a broad framework for considering need. However, in the ﬁ eld of intellectual disabilities a truly holistic assessment will

provide a broad framework for considering need. However, in the ﬁ eld of intellectual disabilities a truly holistic assessment will 
frequently require different theoretical perspectives because of the variability in and complexity of need. The precise form of any focussed assessment will depend on the reasons for undertaking the assessment. The nature of the assessment will vary considerably if it is primarily to determine a person’s social care needs, as opposed to the reasons for a particular problematic behaviour. 
Even with the context of challenging behaviour, the assessments

Even with the context of challenging behaviour, the assessments 
undertaken will vary. Increasingly, the skills expected of those working in community teams supporting people with intellectual disabilities is to be able to recognize what assessments are relevant and required and to be able to undertake such assessments in the community setting where the person with intellectual disability lives. For the sake of clarity, a distinction is made below between those assessments that are fundamentally directed at characterizing the persons, intellectual disability and those whose main focus is on psychiatric and behavioural aspects.
Intellectual disability, its characterization and causes
The term intellectual disability is not in itself a diagnosis as it does not inform in any reliable way about aetiology, prognosis, or speciﬁ  c treatments. Rather, it refers to a clinical state that is devel-

opmental in origin and affects intellectual and social functioning. The diagnosis is the identiﬁ  cation of the underlying cause for the 
observed developmental delay. The extent of early developmental delay can be measured against standardized developmental scales (e.g. Bayley or Grifﬁ  ths Developmental Scales), and during child-
hood and adult life. There are also well-established speciﬁ  c assess-
ments of intellectual, language, and functional abilities. These assessments provide a proﬁ  le of a person or group of people that 
can be compared against the norms for age and a given population. Adaptive functioning has to be measured against what would be expected for a person of that age, and the social and cultural expe-
riences of the person have to be taken into account. The Wechsler 
Scales for IQ, and the Vineland Adaptive Behaviour Scales
(11) or 
the revised Adaptive Behaviour Scales of the American Association for Intellectual and Developmental Disabilities

(11) or 
(12) for characteriz-
ing functioning are established instruments for the measurements of these abilities and for which there are normative data for comparison.
Possible single major causes for an intellectual disability are 
covered in more detail in a separate chapter and are mainly the province of paediatrics or clinical genetics. However, where there is clear evidence for developmental delay in childhood and for the person having an intellectual disability and no obvious cause has been previously established, further investigation is indicated. This will be informed by the clinical history and by physical 
Fig. 10.1.1 Interactions between the components of ICF.Health condition
(disorder or disease)
Body functions
and structuresActivities Participation
Environmental
factorsPersonal

factors10.1 classification, diagnosis, psychiatric assessment, and needs assessment

SECTION 10  intellectual disability (mental retardation) 1822
examination (e.g. presence of a family history of similar disorder or 
not, evidence of the physical characteristics of a particular syn-drome). As part of this process, the developmental history should also establish whether the developmental proﬁ  le is not only charac-
teristic of an intellectual disability but also whether the person meets criteria for having an autistic spectrum condition. This is important because of the high rates of autism within the popula-tion of people with intellectual disability and the implications such a diagnosis may have for the type of support.
(13) Particularly where

(13) Particularly where 
the person has evidence of dysmorphic physical characteristics, a moderate, severe or profound intellectual disability, and/or a family history of disability, chromosomal, biochemical, and/or molecular genetic studies may be indicated. With improving knowledge about the developmental differences and the different predispositions to speciﬁ  c co-morbidities that exist between genetically determined 
syndromes, establishing the cause of a person’s intellectual disability is becoming increasingly important and may help inform psychiatric and psychological assessments.
(14)
(a) Assessments of index problem and psychiatric diagnosis
There have been signiﬁ  cant advances in the conceptual models

(14)
There have been signiﬁ  cant advances in the conceptual models 
used to help understand the occurrence and maintenance of prob-lem behaviours or abnormal mental states in people with intellec-tual disabilities. The following four approaches are particularly relevant and each of these perspectives needs to be considered in any assessment. First, applied behavioural analytical studies have demonstrated how the occurrence of behaviours, such as self-injurious behaviour, can be shaped in the context of particular environmental or individual setting conditions.
(15) This approach 
attempts to identify the ‘functions’ of behaviours. Speciﬁ  c behav-
iour (e.g. self-injurious behaviour, aggressive outbursts etc.) may, for example, be identiﬁ  ed as being attention-maintained or demand

iour (e.g. self-injurious behaviour, aggressive outbursts etc.) may, for example, be identiﬁ  ed as being attention-maintained or demand 
avoidant. Secondly, some behaviours may be a consequence of arrested development. In such cases the behaviour itself (e.g. repet-itive checking) may be similar to that which occurs as part of typi-cal childhood development but it has continued into adult life. Thirdly, the behaviours may be a manifestation of co-morbid physical or psychiatric disorder. For example, as a consequence of increasing irritability and agitation associated with depression
(16)
or consequent upon pain or some other physical distress. Fourthly, the abnormal mental state or behaviour may be associated with the cause of the person’s developmental disability. This is increas-ing referred to as ‘the behavioural phenotype’ of a particular syndrome.
(14) These different models of understanding are not

(14) These different models of understanding are not 
necessarily mutually exclusive. For example, the behaviours and psychiatric problems that commonly affect people with Prader Willi syndrome includes examples of each of the above. The increased propensity to temper outbursts and to repetitive and rit-ualistic behaviours are likely to be partly a consequence of arrested development and to be partly re-inforced and modiﬁ  ed depending 
on environmental contingencies, the over-eating behaviour is a direct consequence of the syndrome and, if obesity is not prevent-ed, it can lead to physical illness that may present with changes in behaviour (e.g. sleep disorders), and those with one genetic form of the syndrome have a high risk for developing co-morbid affective psychotic illness.
(17,18)  In case of each of these examples, rather dif-

ferent approaches will be required, varying from environmental change to the possible prescription of medication to treat co-morbid psychiatric illness. Assessments should therefore be informed by these different theoretical perspectives recognizing that similar 
‘behaviours’ may have different aetiologies and that what pre-disposes to, precipitates, or maintains a particular behaviour and/or mental state may each be different. The challenge of assessment is to identify the developmental, biological, psychological, and social factors that relevant and the treatment/management implications.
In psychiatric practice, the referrals and the assessments are usu-

ally to determine the reasons for the occurrence of a particular maladaptive/challenging behaviour and/or apparent change in mental state or in cognitive and functional ability. The focus of the assessment is therefore to address these issues but, in doing so, it invariably requires an assessment of the developmental proﬁ  le of 
the person concerned and consideration of the cause of any such 
disability. In principle, however, the psychiatric assessment of 
people with intellectual disability is not dissimilar to that under-taken in general child or adult psychiatry. The main differences are as follows:
1 Special care may have to be taken in assessing an individual’s 
mental and cognitive state and whether this has changed over time and, where language development is impaired, a greater reli-ance may have to be placed on information from an informant;
2 a good developmental history is essential to map early develop-

ment and the potential developmental origins of the individual’s present state;
3 it is important to investigate the enabling and constraining 
aspects of a person’s environment that facilitate or impinge on a person’s life and thereby how environmental change might bring real beneﬁ  t;
4 the possibility of multiple physical and mental health problems 
and the potential for complex interactions between the individual and his or her carers and the immediate and distant environment 
should be appreciated.
5 where co-morbidity is a possibility, evidence of a change in 
physical and mental state or behaviour or an exaggeration of previous states (e.g. obsessional behaviours) that might be indic-ative of the development of a physical or psychiatric illness must be enquired about. The development of physical illness may also manifest as behavioural change.
Psychiatric assessment is therefore invariably an iterative process,

Psychiatric assessment is therefore invariably an iterative process, 
especially so with the uncertainties associated with the assessment of a person with an intellectual disability and the different concep-tual models. In undertaking an assessment it can be helpful to draw a distinction between:
1 the characterization of the nature and extent of the person’s 
intellectual disability and the identiﬁ  cation of its aetiology;
2 the identiﬁ  cation of the onset, nature and extent of additional 
problem behaviours or abnormal mental states;
3 the determination of the possible aetiological factors of the per-
son’s behaviour, such as whether there is a co-morbid psychiatric diagnosis or whether there are particular factors that might have predisposed to, precipitated and are now maintaining a particu-lar behaviour or abnormal mental state.
A detailed history taking from both the person him- or herself 
and an informant covering both childhood development and

1823
the presenting problem, a mental state examination and where 
indicated a physical examination, direct observation, and often detailed record keeping of particular behaviours (depending on the reason for referral) by care staff over time are the key components of a comprehensive assessment. Where referrals are about the occurrence of problem behaviours, the assessments should include a description of the behaviour as well as an attempt to identify those factors that might increase or decrease the likelihood of the behaviour occurring. These will include the identiﬁ  cation of those 
factors affecting the person him- or herself and those that are particular to the environment. Speciﬁ  cally from a psychiatric per-
spective, this includes the identiﬁ  cation of psychiatric or physical 
illnesses, the relationship of the index behaviour to any change in mental state or, for example, the occurrence of seizures, as well as

illnesses, the relationship of the index behaviour to any change in mental state or, for example, the occurrence of seizures, as well as 
the possible contribution of the developmental disability to the 
problem. For example, the presence of autism may account for observed ritualistic and obsessional behaviours and might also help to make sense of a person’s aggressive outbursts that staff observa-tion and record keeping over time has shown occurs at times of unexpected change in routine or activity. Knowledge about the chronicity of a particular behaviour might inﬂ  uence the under-
standing of the likely contributory factors that give rise to that behaviour. If the behaviour is of recent onset then the role of recent life events or the possibility that the person has developed a mental or physical illness should be investigated. However, if the behaviour has been present since early childhood, psychological models of understanding may be more relevant.

In terms of assessment instruments, a clear distinction needs to 
be drawn between those that are essentially descriptive in nature and those that are investigating the potential aetiology of the index behaviour. The former include, for example, the Aberrant Behaviour Checklist
(19) and the latter, which are based on particular theoreti-
cal models, may include, for example, the Psychiatric Assessment Schedule for Adults with Developmental Disorders
(20) (a struc-
tured assessment of mental state) and the Motivational Assessment Scale
(15) (a structured assessment of the possible ‘functions’ of 
particular behaviours).
Mental state examination
Central to the practice of psychiatry in particular is the identiﬁ  ca-
tion of speciﬁ  c mental phenomena that, when clustered together, 
are indicative of a speciﬁ  c psychiatric disorder. The gold standard 
for diagnoses are the diagnostic manuals ICD-10 and DSM-IV . Diagnostic criteria have also been modiﬁ  ed to better ﬁ  t what is

for diagnoses are the diagnostic manuals ICD-10 and DSM-IV . Diagnostic criteria have also been modiﬁ  ed to better ﬁ  t what is 
observed when assessing people with intellectual disabilities. These have been based on the ICD-10, (DC-LD).
(21) The process is 
two-staged and includes ﬁ  rst a detailed history and mental state 
examination that establishes whether there has been a change in a person’s mental state and if so, the characteristics of the change, and secondly, a comparison of these changes against diagnostic cri-teria to establish the presence or not of speciﬁ  c psychiatric disor-
ders. Investigations may be necessary where there is uncertainty or other possible causes for what is observed need to be ruled out as part of the differential diagnosis.
For people with intellectual disabilities with spoken language, 
disorders such as schizophrenia present in similar ways to the general population, with the onset of the characteristic mental phenomena.

 (22) Similarly, disorders such as Alzheimer’s disease 
can be diagnosed using very similar criteria, although the early features may be different.(23) In each of these examples, greater 
emphasis may have to be placed on informant observation, as some people with intellectual disabilities may have difﬁ  culty with con-
cepts such as mood and with being able to describe the presence or not of abnormal mental phenomena.
The key to mental state examination and psychiatric diagnosis in

The key to mental state examination and psychiatric diagnosis in 
people with intellectual disabilities is to be able to characterize the nature of any observed change. The assessment of mood, sleep, appetite, and concentration may be relatively easy as carers observe increasing distress, tearfulness, and agitation over time in the context of sleep and appetite changes, therefore giving rise to the suspicion of the presence of an affective disorder. Similarly, carers may observe personality and memory changes suggestive of dementia. The presence of hallucinations or delusions may have 
to be inferred by the development of odd behaviour that might

to be inferred by the development of odd behaviour that might 
reasonably be interpreted as responses to abnormal mental experi-ences, such as appearing to respond to auditory hallucinations. Family or other carers who have known the person for some time may well be able to describe more subtle mental state abnormalities such as a deterioration in a person’s ability to express his or her thoughts indicating the possibility of thought disorder, or increas-ing perplexity or evidence of paranoid ideas. The interpretation of cognitive ﬁ  ndings is more difﬁ  cult because of the pre-existing intel-
lectual impairments, but clear documentation of cognitive abilities is important as further deterioration or evidence of improvement over time can be very informative.

A full needs assessment brings together the identified social, emotional, and health needs of an individual, including an under-standing of the wishes of the person and views of other people who are concerned for and involved in the support and care of that individual. This whole process has, over the last few years in both mental health and intellectual disability services, become more formalized through ‘needs-led assessments’ and sometimes through the ‘care programme approach’ . Person-centred planning is the process by which this information is brought together in a manner that directs the allocation of support and any necessary treatment interventions.
(24)
Social services are in general responsible for undertaking assess-

(24)
ments at key transitions (e.g. prior to the end of statutory educa-tion) or if there is evidence that need has changed. If the person lacks the capacity to express his or her view then the question of what is in the person’s best interests should be determined. The balance that this process is attempting to achieve is to respect the wishes of the person concerned and to balance an adult’s right to autonomy, on the one hand, versus the need for care and support, on the other. More recently, the critical importance of assessing a person’s ability to make decisions about his or her own life and the pivotal role of a person’s ‘decision-making capacity’ in achieving the correct balance between the respect for autonomy and the need for care and support has received more attention. Legislation has been enacted ﬁ  rst in Scotland and more recently in England and

Wales that provides the framework for intervention where the per-
son concerned lacks the capacity to make the relevant decision for him/herself. The assessment of a person’s decision-making capacity requires an evaluation of a person’s ability to understand and use information relevant to the decision, retain and balance the neces-sary information and then to communicate a choice.
(25)10.1 classification, diagnosis, psychiatric assessment, and needs assessment

SECTION 10  intellectual disability (mental retardation) 1824
Although there is clearly an overlap, it can be helpful to distin-
guish between social care, educational, and health-care needs. In the case of children, the need for special education and for family support are likely to be central, depending on the extent of the disability and any other associated disabilities. For adults, accom-modation with an appropriate level of support, meaningful day-
time occupation, and companionship and practical help according

to need will be key. Systematic assessments provide a structured way to determine whether a low, medium, or high service environ-ment will best meet an individual’s needs. The types and range of services that need to be provided are covered in other chapters. Health-care needs will include the same as those of the general population but high rates of physical and sensory impairments, mental health and behavioural problems, and impairment in com-munication are all likely to give rise to additional needs. Particularly for those people with more severe intellectual disabilities and limited and/or no language, there is also a clear responsibility for carers to ensure a healthy lifestyle, health screening, and to help identify health-related problems when they do occur. Special help may be required to ensure access to both primary and secondary health-care services and to ensure the person understands what is happening to them. This will include questions of consent to health treatment and

to ensure access to both primary and secondary health-care services and to ensure the person understands what is happening to them. This will include questions of consent to health treatment and how a person with intellectual disabilities can be best helped to give maximally informed consent or at least be able to assent when it is in his or her best interests to do so. A structured process of assessment, paying attention to the cause of the intel-lectual disability and its associated problems and the extent and nature of other impairments, disabilities, and handicaps will mini-mize the risk that health-related problems might go unnoticed or that social care needs might be ignored.

Emerson, E. (2001). Challenging Behaviour: Analysis and intervention in 
people with severe intellectual disabilities . Cambridge University Press, 
Cambridge. 
Bouras, N. and Holt, G (eds.). (2007). Psychiatric and Behavioural Disorders 
in Intellectual and Developmental Disabilities . Cambridge University 
Press, Cambridge. 
 1. Department of Health. Valuing People: a new strategy for the 
21st Century , Department of Health, London
 2. United Nations. (2007). Convention on the Rights of People with 
Disabilities .
 3. Beange, H., McElduff, A., and Baker, W. (1995). Medical disorders of 
adults with mental retardation: a population study. American Journal of 
Mental Retardation ,99, 595–604.
 4. Cooper S.A., Smiley E., Morrison J., et al. (2007). Mental ill-health in 
adults with intellectual disabilities: prevalence and associated factors. 
British Journal of Psychiatry ,190, 27–35.

4. Cooper S.A., Smiley E., Morrison J., et al. (2007). Mental ill-health in 
 5. Lowe, K., Allen, D., Jones, E., et al. (2007). Challenging behaviours: 
prevalence and topographies. Journal of Intellectual Disabilities 
Research ,51, 625–36.
 6. Verkerk, A., Pieretti, M., Sutcliffe, J.S., et al. (1991) Identiﬁ  cation of a 
gene (FMR–1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. 
 7. American Psychiatric Association (1994). Diagnostic and statistical 
 8. World Health Organization (2001). International Classiﬁ  cation of 
Functioning, Disability and Health (ICF) . World Health Organization, 
Geneva.

Geneva.
 9. World Health Organization (1980). International classiﬁ  cation of 
impairments, disabilities and handicaps  (10th revision). World Health 
10. World Health Organization (1992). International statistical classiﬁ  cation 
of diseases and related health problems , (10th revision). WHO, Geneva.
11. Sparrow, S., Ball, D., and Cicchetti, D. (1984). Vineland Adaptive 
Behaviour Scale  (Interview Edition–Survey Version). American 
Guidance Association, Circle Pines, MN.
12. Nihara, K., Leland, H., and Lambert, N. (1993). Adaptive Behavior 
Scales–Residential and Community  (2nd edn). Pro–Ed, Austin, TX.
13. Shah, A., Holmes, N., and Wing, L. (1982). Prevalence of autism and 
related conditions in adults in a mental handicap hospital. Applied

related conditions in adults in a mental handicap hospital. Applied 
Research in Mental Retardation ,3, 303–17.
14. Editorial by Oliver, J..and Hagerman, R. (2007) Trends and challenges 
in behavioural phenotypes. JIDR ,51, 649–52
15. Durrand, V .M. and Crimmins, D.B. (1988). Identifying the variables 
maintaining self-injurious behaviour. Journal of Autism and 
Developmental Disorders ,18, 99–117.
16. Meins, W. (1995). ‘Symptoms of major depression in mentally retarded 
adults’ Journal of Intellectual Disability Research ,39, 41–46.
17. Holland, A.J., Whittington, J.E. Butler, J., Webb, T., Boer, H and 
Clarke, D.J. (2003) Behavioural phenotypes associated with speciﬁ  c 
genetic disorders: evidence from a population-based study of people with Prader-Willi Syndrome. Psychological Medicine, 33, 141–53
18. Boer, H., Holland, A.J., Whittington, J., Butler, J., Webb, T. and Clarke, D.

18. Boer, H., Holland, A.J., Whittington, J., Butler, J., Webb, T. and Clarke, D. 
(2002) Psychotic illness in people with Prader Willi Syndrome due to 
chromosome 15 maternal uniparental disomy The Lancet ,
359, 135–36.
19. Aman, M., et al. (1985). The Aberrant Behavior Checklist: a behavior 
rating scale for the assessment of treatment effects. American Journal of 
Mental Deﬁ  ciency ,89, 485–91.
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moderate and severe learning disability (mental retardation). Part 1: Developmental and reliability of the patient interview (the PAS-ADD). British Journal of Psychiatry ,163, 471–80.
21. Cooper, S.-A., C. Melville, et al. (2003). ‘Psychiatric diagnosis, 
intellectual disabilities and diagnostic criteria for psychiatric disorders for use with adults with learning disabilities/mental retardation (DC-LD)’ . Journal of Intellectual Disability Research ,47, 3–15.

22. Meadows, G., Turner, T., Campbell, L., et al. (1991). Assessing 
schizophrenia in adults with mental retardation. A comparative study. British Journal of Psychiatry ,158, 103–5.
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CAMDEX informant interview is a valid and reliable tool for use in the diagnosis of dementia in adults with Down’s syndrome. Journal of 
Intellectual Disability Research ,48(6), 611–20.
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health care decisions: Its importance in clinical practice. Psychological 
Medicine ,29 (2): 437–46.

10.2
Prevalence of intellectual 
disabilities and epidemiology of mental ill-health in adults with intellectual disabilities
Prevalence of intellectual disabilities
If intelligence quotient (IQ) was normally distributed in the popu-
lation, with a mean of 100 and standard deviation of 15, then about 2 per cent of the population would have an IQ below 70. However, reported rates vary widely depending on the deﬁ  nition of 
intellectual disabilities used, the country and region of study, the time of the study, the age range and ethnicity of the population, and the method of population ascertainment.
(1–3)
Deﬁ nition
ICD-10 and DSM-IV-TR deﬁ  nitions of intellectual disabilities are 
similar:
◆ signiﬁ  cantly sub-average intellectual functioning (IQ below 
approximately 70; mental age less than 12 years);
◆ concurrent impairments in present adaptive functioning; diminished ability to adapt to the daily demands of the social 
environment;

◆ onset before the age of 18 years.
IQ is a continuous measure, so when basing a deﬁ  nition of 
intellectual disabilities upon it the threshold is arbitrary, and changes in threshold can have a large impact on prevalence. For example, in the past the American Association on Intellectual and Developmental Disabilities’ criteria had an IQ threshold of 84. This was subsequently changed to 70 in 1973, and then to 70–75 in 1992. ICD-10 and DSM-IV-TR deﬁ  nitions are not statistical construc-
tions; the requirement of impaired adaptive functioning may half estimated prevalence rates compared with a statistical deﬁ  nition. 
Furthermore, different methods to assess intelligence and adaptive behaviour can lead to different prevalence rates.
Country and region

Prevalence of intellectual disabilities is reported to be much higher in developing than developed countries, due to socio-economic factors, although mild intellectual disabilities may possibly be less 
disadvantaging in non-literate societies. Iodine deﬁ  ciency is the

disadvantaging in non-literate societies. Iodine deﬁ  ciency is the 
most common preventable cause of intellectual disabilities world-wide, and is indigenous in some regions of Asia and Africa. Exposure of populations to heavy metals and toxins can lower the average population IQ by a few points, hence some people who would otherwise have had low-average ability move into the intellectual disabilities range. Regions with a high level of consan-guineous marriages can also have higher prevalence. For example, Tay-Sachs disease is prevalent amongst Ashkenazi communities, although premarital genetic counselling has markedly reduced it in the United States. The availability and sophistication of antenatal, perinatal, and neonatal care account for some differences between countries. Some studies show differences in ethnic groups, although the cultural suitability of the measures used may have contributed to these ﬁ  ndings.
Time
Prevalence varies with time, due to preventative measures,

Time
Prevalence varies with time, due to preventative measures, 
and social developments. In developed countries, an increase in prevalence was seen in the early 1960s, with falling prevalence thereafter, due to developments in neonatal care with increasing survival of very low birth weight infants. Down syndrome is the most common chromosomal disorder causing intellectual disabili-ties, and survival rates of neonates and children with Down syn-drome have increased substantially in recent decades, primarily due to access to surgery for congenital heart disease. The wide-spread introduction of antenatal screening for Down syndrome might have been expected to reduce the population prevalence of Down syndrome through lowering birth rate, but rising maternal age at birth, and increasing life expectation counter this, and there appears to be little change in the population prevalence. The wide-spread introduction of antenatal screening for phenylketonuria in

the 1960s, and congenital hypothyroidism in the 1970s has virtu-
ally eliminated intellectual disabilities due to these conditions in

SECTION 10  intellectual disability (mental retardation) 1826
developed countries. Better living conditions, with individualized 
packages of support, and a political agenda for social justice and equality of access to health care and supports may all have contributed to the increasing life expectation for people with intellectual disabilities, although this is still lower than that of the general population. Increasing maternal age and increasing maternal alcohol consumption are expected to lead to higher birth rate of infants with foetal alcohol syndrome, and genetic causes of intellectual disabilities. Overall, there appears to have been little change in prevalence compared with 50 years ago.
Age
Prevalence is higher in child than adult cohorts, and lower in older than younger adult cohorts, with the highest prevalence at around age 10 years. This is due to intellectual disabilities having been identiﬁ  ed by this age, combined with an earlier age of death for

persons with intellectual disabilities compared with the general population. Children with the mildest intellectual disabilities are likely to beneﬁ  t from additional support for learning at school, but 
will develop skills and experience over time, such that some no longer meet criteria for intellectual disabilities in adulthood.
Ascertainment
Reported prevalence varies with the methods of population ascertainment. For children, the ascertained prevalence doubled compared with case registers, when record linkage to education department data on educational attainments was included (giving an estimated prevalence of 1.4 per cent).
(3) There was a dispropor-

tional increase in indigenous Australian children, who were possibly false positives. For adult populations, only a proportion with intellectual disabilities will be in contact with specialist health services for adults with intellectual disabilities. Ascertainment is higher when data is combined from primary health care, specialist health services, and social services, if the provision of day opportu-nities, supported work, respite care, funded support packages, and direct payments is considered. This is likely to identify almost all persons with moderate to profound intellectual disabilities, and adults with mild learning disabilities receiving support; it will not identify adults with IQ below 70 who no longer have impaired adaptive functioning (who therefore do not meet ICD-10 or DSM-IV-TR criteria for intellectual disabilities) and do not need support, 
or some people who receive all their support exclusively from

or some people who receive all their support exclusively from 
unpaid carers. The assessment of IQ (culturally sensitive), adaptive functioning and support needs, plus medical assessment, of all individuals within a whole population or a representative sample would provide accurate prevalence data for that time point and area. However, this would be a substantial undertaking, in view of the tens or hundreds of thousands of participants required.
There have been many studies of prevalence of intellectual disabilities. For the reasons above, there is substantial variation in reported prevalence in developed countries, varying from 2 to 85/1000 general population, and there are few robust studies in developing countries. Less variability is found between studies of moderate to profound intellectual disabilities. Given the variation, it is inappropriate to provide average ﬁ  gures from across the studies.

Interpreting the literature, we suggest that prevalence of intellectual disabilities in the United Kingdom may be in the order of 9–14/1000 childhood population, and 3–8/1000 adult population, varying 
with time and geography. However, it should be noted that the 
ﬁ gure of 2 per cent is frequently assumed. Intellectual disabilities 
are more prevalent in males than females, particularly amongst children, young- and middle-aged adults: the reported ratio varies between 1:1 and 2:1. At older age, the gender ratio equalizes due to greater life expectancy of women compared with men (mirroring the general population), and at extreme old age, women may even outnumber men. The distribution of level of intellectual disabili-ties varies with age, due to the shorter life expectancy of people with more severe intellectual disabilities. Mild intellectual disabili-ties are associated with socio-economic status. These issues are explored in greater depth elsewhere.
(1,2)

(1,2)
Prevalence and incidence of adult 
mental ill-health
Some genetic causes of intellectual disabilities have specific 
behavioural phenotypes. For example, Down syndrome confers protection from mania, and problem behaviours, whilst increasing risk for dementia, Prader Willi syndrome is associated with affec-tive psychosis, and velo-cardio-facial syndrome increases risk for psychosis. Behavioural phenotypes are considered in greater depth in Chapter 10.4. In this section we consider mental ill-health of adults with intellectual disabilities of all causes.
Study methodologies

Mental ill-health is thought to be commonly experienced by adults with intellectual disabilities. Many of the existing prevalence studies have methodological limitations, accounting for the wide discrepancy in reported prevalence which ranges from 7 to 97 per cent. Limitations have included biased sampling; reliance upon existing case-note information, or instruments designed as screening tools only; lack of information on the extent of detail within assessments, the instruments, or diagnostic criteria used; and population-based studies limited by small cohort sizes. Other limitations include failure to indicate whether rates are lifetime, point, or period prevalence; reporting combined prevalence for children and adults; reporting mental ill-health in total, but not describing nor being comprehensive as to what is, and what is not, included (particularly with regards to problem behaviours, autistic spectrum disorders, attention-deﬁ  cit hyperactivity disorder, and anxiety disorders);

as to what is, and what is not, included (particularly with regards to problem behaviours, autistic spectrum disorders, attention-deﬁ  cit hyperactivity disorder, and anxiety disorders);

and studying selected subgroups such as only adults with verbal 
communication skills. All of these points must be carefully consid-ered when interpreting and drawing conclusions from the existing literature.
Prevalence of mental ill-health varies, depending upon the diag nostic
criteria employed. This is because many of the diagnostic catego-ries within The ICD-10 Classiﬁ  cation of Mental and Behavioural 
Disorders: Diagnostic Criteria for Research  (DCR), and the DSM-IV-
TR contain criteria that cannot be met due to the person’s degree of intellectual disabilities and communication skills, and do not include other criteria that are important in this population. For these reasons, Diagnostic Criteria for Psychiatric Disorders for Use 
with Adults with Learning Disabilities/Mental Retardation  (DC-LD) 
was developed for use speciﬁ  cally with this population. These, and

1827
other important diagnostic issues are explored in further depth 
elsewhere.(4)
Population-based studies where participants received a psychiatric assessment are shown in the Table 10.2.1. 
(5–9) A high prevalence of 
mental ill-health was reported in all but Lund’s study, which used assessment methods which would today be considered limited.
(6)
Point prevalence is higher than that observed in the UK general population. Speciﬁ  c types of mental ill-health with a higher preva-
lence compared with the general population including problem behaviours, autism, dementia, bipolar disorder, and psychoses. Dementia is part of the behavioural phenotype of Down syndrome, and also occurs three to four times more commonly amongst people with intellectual disabilities of other causes.
(10,11) Bipolar

(10,11) Bipolar 
disorder occurs at about double the prevalence of that reported for the general population. This is despite a high proportion of people (about 25 per cent) taking mood-stabilizing drugs (typically for epilepsy management). Depression is either more prevalent, or occurs at the same rate, depending upon the criteria used. Prevalence of non-affective psychotic disorders (including schizo-affective disorders) has consistently been reported to be higher than for the general population; a recent study found a point pre-valence of 4.4 per cent including schizophrenia, in remission, or 4.0 per cent for psychosis, currently in episode. Problem behaviour is the most prevalent type of mental ill-health at 22.5 per cent (Consultant psychiatrist’s opinion) or 18.7 per cent (DC-LD) in the most recent of the studies.
(9)
Given the numerous biological, psychological, social, and devel-

(9)
opmental disadvantages experienced by adults with intellectual disabilities compared with the general population, a higher preva-lence of mental ill-health is expected. The higher prevalence of bipolar disorder and of psychosis points to biological origins yet to be determined, and likely to be of relevance to the whole general population.
Incidence
There has been limited study of the incidence of mental ill-health in adults with intellectual disabilities. Longitudinal studies in the general population have not included persons with moderate to profound intellectual disabilities, but have demonstrated the higher prevalence of symptoms of depression and anxiety in adults 
with mild intellectual disabilities compared with the general popu-lation.
(12,13)  A recent study of a population-based cohort of 
651 adults with intellectual disabilities found that incidence varied, depending upon the criteria used.

(14) According to the Consultant 
psychiatrists opinion, the 2-year incidence of mental ill-health (of all types, except speciﬁ  c phobias) was 16.3 per cent (12.6 per cent 
excluding problem behaviours, and 4.6 per cent for problem behaviours), giving a standardized incident ratio for common mental disorders of 1.87 (95 per cent CI = 1.51–2.28). The com-parison general population data was broadly similar, but not identical in its classiﬁ  cation. The episodes with most frequent inci-
dence were affective disorders at 8.3 per cent, followed by problem behaviours. The incidence of episodes of psychosis over the 2-year period was 1.4 per cent, of which 0.5 per cent were ﬁ  rst episodes

of psychotic disorders, giving a standardized incidence ratio of 10.0 (95 per cent CI = 2.1–29.3). The rate of full remission from an episode of psychosis within the 2-year period was low, at 14.3 per cent. The authors concluded that the high point prevalence of mental 
ill-health is explained by both a high incidence and high level 
of enduring mental ill-health, with slightly more enduring than incident cases.
Protective and vulnerability factors
Many of the factors that might afford protection from or increase vulnerability for mental ill-health are interrelated, for example level of ability, age, gender, and epilepsy. Few studies have attempted to tease these apart. Further work in this area is important, particu-larly as the pattern of related factors appears to differ from those found in the general population, suggesting that inferences cannot necessarily be drawn from general population data.
Ability

Ability
The relationship between ability level and mental ill-health has variously been reported to be absent, present with higher preva-lence of mental ill-health at lower ability levels, or present with higher prevalence of mental ill-health at higher ability levels; these differences are explained by the limitations in the previous litera-ture, as described above. Recent reports suggest lower ability is associated with mental ill-health in general, and speciﬁ  cally with 
Table 10.2.1  Prevalence of mental ill-health among adults with intellectual disabilities
Study Sample size Ability Diagnostic criteria Prevalence (%)*
Corbett (1979)(5)  402 Borderline-profound intellectual disabilities ICD-8 46.3†
Lund (1985)(6) 302 Borderline-profound intellectual disabilities Modiﬁ  ed DSM-III 28.1
Cooper and Bailey (2001)(7) 207 Mild-profound intellectual disabilities Modiﬁ  ed DCR 37.0
Deb et al. (2001)(8)  101 Mild-moderate intellectual disabilities ICD-10 14.4‡

Cooper et al. (2007)(9) 1023 Mild-profound intellectual disabilities Psychiatrists opinion
DC -LD
DCR
DSM-IV-TR40.9
35.2
16.6
15.7
*Excluding speciﬁ  c phobias.
†Excluding dementia.
‡Excluding problem behaviours, personality disorder, dementia, autism, alcohol problems, schizophrenia not in episode, and bipo lar disorder not in episode.10.2 prevalence of intellectual disabilities and epidemiology of mental ill-health in adults

SECTION 10  intellectual disability (mental retardation) 1828
problem behaviours, but not depression nor psychosis; and that 
lower ability also predicts incident problem behaviours.(6,7,9,14)
However, diagnostic complexities may contribute to the lack of association between lower ability and some disorders.
Age
The prevalence and incidence of dementia is higher with increasing age. Whilst it has been suggested that problem behaviours are more prevalent at younger ages, there is no consistent evidence to support this. Of the population-based studies quoted above, no relationship was found between age and mental ill-health.
Gender
Autism and attention-deficit hyperactivity disorder are more common in males. Most studies have not otherwise found any association between gender and mental ill-health in this popula-tion, unlike the general population. A higher prevalence of prob-lem behaviours has been reported in women,
(8,9) but aggression

(8,9) but aggression 
has also been reported as more common in men(15); these differ-
ences might possibly be due to whether the independent effects of gender and autism are investigated. Women have been reported to score higher than men on the ‘affective/neurotic disorders’ sub-domain of a screening tool,
(16) and to have a higher prevalence of 
mental ill-health,(9) and speciﬁ  cally depression; however, within 
the same cohort gender did not predict incident mental ill- health.(14)
Epilepsy and other physical ill-health
There are conﬂ  icting ﬁ  ndings regarding whether there is a relation-
ship between epilepsy and mental ill-health in this population, with the interaction between level of ability and epilepsy and use of antiepileptic drugs possibly contributing. It remains unclear whether physical and mental ill-health are related.

Associations have been demonstrated between preceding life events in adults with intellectual disabilities and scores for ‘affective/neu-rotic disorders’ , and between life events and scores on the Developmental Behaviour Checklist for Adults .
(17) A relationship has 
been reported with mental ill-health in general, and speciﬁ  cally 
with depression, but not psychosis, nor problem behaviours, nor incident mental ill-health (excluding problem behaviours),
(9,14)
but has been reported for incident problem behaviours.(14)
Accommodation/support
Both prevalence and incidence of mental ill-health, and of problem behaviours, is related to living in a setting other than with family carers, and this is independent of past psychiatric history. This highlights the need for engagement between professionals, service managers, and paid carers.
Deprived localities

Unlike for children, no relationship had been found between area-based measures of deprivation and mental ill-health in the adult population with intellectual disabilities, although there have been few investigations of this. It is possible that adults with intellectual disabilities may not have the same lifestyle characteristics as the general population living in the same area, due to being ‘placed’ in areas dissimilar from those they originated from and within which 
they acquired life-long habits and preferences, and through on-going important relationships with family members whose own views and actions may be of greater inﬂ  uence than those of their 
paid carers or local community. It may be that the biological, social, and developmental causes and consequences of intellectual disabil-ities far outweigh some of the factors of relevance to the general population, in the aetiology of mental ill-health. This requires further study.
Smoking

Smoking
As for the general population, smoking is associated with mental 
ill-health, and speciﬁ  cally with depression and psychosis.
Other factors which may be independently related to mental ill-
health in this population include urinary incontinence (as in the general population), not being immobile, visual impairment (for psychosis, as for the general population), abuse, neglect and exploi-tation, and parental divorce during childhood. However, few studies have investigated these factors. Few people with intellectual disabilities use alcohol or cannabis, so it is not known if there is any relationship between these behaviours and mental ill-health in this population.
◆ The prevalence of intellectual disabilities varies, depending upon deﬁ  nition, country, time, age range, and methods of popu-

lation ascertainment. Reported rates vary substantially, and may be in the order of 9–14/1000 childhood populations, 3–8/1000 adult populations in developed countries, and higher in developing countries.
◆ Mental ill-health is more commonly experienced by adults with intellectual disabilities than the general population. Point preva-lence is about 40 per cent, with problem behaviours being the most prevalent type.
◆ Dementia, problem behaviours, autism, bipolar disorder, and psychoses are more prevalent than for the general population.
◆ Incident mental ill-health is also greater than for the general population, at about 8 per cent per year. Common mental disor-ders and psychoses both have higher incidence than that for the general population.
◆ There is limited information on the protective and vulnerability factors for mental ill-health.

◆ Some factors related to prevalence and incidence of mental ill-health are similar to those found in the general population suggesting similar underlying causative mechanisms, but other factors differ, suggesting that inferences cannot necessarily be drawn from general population data and applied to the popula-tion with intellectual disabilities.
◆ Identifying high-risk groups within the population may allow for the provision of early interventions and supports, whilst some causative factors may be amenable to interventions to prevent or improve mental ill-health in this population. We need to gain a better understanding of these issues.

1829
NHS Health Scotland. (2004). Health needs assessment report. People with 
learning disabilities in Scotland . NHS Health Scotland, Glasgow.
Royal College of Psychiatrists. (2001). DC-LD [diagnostic criteria for 
psychiatric disorders for use with adults with learning disabilities/mental retardation] . Gaskell Press, London.
Smiley, E. (2005). Epidemiology of mental health problems in adults 
with learning disability: an update. Advances in Psychiatric Treatment ,
11, 214–22.
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adults with learning disabilities—prevalence and relationship to ability 
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and associations with mental ill-health in adults with intellectual 
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10. Cooper, S.-A. (1997). High prevalence of dementia amongst people 
with learning disabilities not attributed to Down’s syndrome. Psychological Medicine ,27, 609–16.
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11. Strydom, A., Livingston, G., King, M., et al.  (2007). Prevalence of 
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retardation: psychosocial functioning in adulthood. Psychological 
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Disability Research ,49, 839–44.10.2 prevalence of intellectual disabilities and epidemiology of mental ill-health in adults

10.3
Aetiology of intellectual 
disability: general issues and prevention
Causation
The complexity of causes
Intellectual disability can follow any of the biological, environmen-
tal, and psychological events that are capable of producing a decline of cognitive functions. Some factors do not directly or inevitably cause intellectual disability but add to the effects of a previous pri-mary cause. Genetic causes may be hereditary or non-hereditary, and may or may not produce speciﬁ  c syndromes. Some lead to 
inborn errors of metabolism.
(1)
Neurological symptoms during the neonatal period are strongly 
associated with prenatal developmental disturbances. For example in maternal pre-eclampsia, placental insufﬁ  ciency may lead to

(1)
associated with prenatal developmental disturbances. For example in maternal pre-eclampsia, placental insufﬁ  ciency may lead to 
malnutrition, foetal asphyxia, intrauterine growth retardation and prematurity, and subsequently to perinatal problems including asphyxia, intracranial haemorrhage, hyperbilirubinaemia, and hypoglycaemia. It is important to detect these coexisting condi-tions, because their effects may add to or interact with those of the primary cause.
(2)
The biomedical cause  of intellectual disability may lead to addi-
tional disorders or disabilities , or may itself be progressive.(1–3)
In fact, intellectual disability exists commonly with many other 
symptoms in a patient, for example with sensory problems, dys-phasia, cerebral palsy, epilepsy, or autism. These additional factors affect opportunities for gaining experiences necessary for develop-

ment . Activity may be restricted by sickness, or the effects of medi-
cation. Motor disability may reduce mobility, or cause dysphasia. Sensory impairment may restrict vision or hearing. These restric-tions add to the effects of the primary cause and interact with envi-ronmental and emotional factors to retard the development of the individual.
(1–4)
How often do we know the cause(s)?
The various concepts of intellectual disability and its causes have led to different epidemiological estimates . The population at risk 
consists of survivors, but some ﬁ  gures include also all live born. 
Differences in the deﬁ  nition and detection of cases, the classiﬁ  cation 
system used, the population studied, the timing of the study in relation to measures of the general population, the resources

system used, the population studied, the timing of the study in relation to measures of the general population, the resources 
available for the study, and sources of the data make it difﬁ  cult to 
compare both the frequency of persons with intellectual disability and the frequency of various causes obtained in different studies. However, a speciﬁ  c cause for intellectual disability can be identiﬁ  ed 
for approximately 80 per cent for persons with severe intellectual disability (IQ <50, includes the groups of moderate, severe, and profound intellectual disability in ICD-10) and 50 per cent of 
persons with mild intellectual disability. The principal cause of 
intellectual disability is estimated to be prenatal in 50 to 70 per cent, perinatal in 10 to 20 per cent, and postnatal in 5 to 10 per cent of persons.
(3–7) In general, knowledge of aetiologies is more accurate 
for people with severe intellectual disability than for those with mild intellectual disability.
(8, 9)

(8, 9)
Classifying causes
The causes of intellectual disability may be classiﬁ  ed according to 
the particular clinical entity, the causative agent or presumed cause, or the timing of the causative factor . The newer and more successful 
classiﬁ  cation systems are based on timing.
(10) The principle is bio-
medical in nature and it is intended to elucidate the earliest factor
that has affected the development of the central nervous system. 
The discovery of the primary cause (or sequential causes) aids 
family counselling and may lead to identiﬁ  cation of a preventable 
general risk.
Viewed in this way, diagnoses can be divided into six main groups 
according to the probable cause and the timing of damage to the central nervous system (Table 10.3.1)
 (11):
◆ genetic causes;

 (11):
◆ central nervous system malformations of unknown origin;
◆ external prenatal factors;
◆ disorders acquired in the paranatal* period;
◆ disorders acquired postnatally; and
◆ untraceable or unclassiﬁ  ed causes.
*The paranatal period is deﬁ  ned as the period from 1 week before 
birth to 4 weeks after birth.

1831
(a) Genetic causes
Chromosomal disorders  include all intellectual disability caused 
by a proven chromosomal aberration or a clinically obvious chro-mosomal syndrome such as Down syndrome. However, chromo-some analysis should be performed in Down syndrome because translocation, mosaicism, or other abnormalities are found in 5 per cent of cases. Chromosomal anomalies associated with intel-lectual disability account for up to 40 per cent of severe cases, and 10 to 20 per cent of mild cases.
(3,6,12,13)  However, the detection 
rates for chromosome abnormalities with the novel molecular karyotyping methods, such as micro array -based comparative 
genomic hybridization ( array CGH ), range from 5 to 17 per cent 
in individuals with normal results from prior routine cytogenetic testing.
(14) Array CGH has the ability to detect any genomic 
imbalance including deletions, duplications, aneuploidies, and ampliﬁ  cations.
Malformations due to microdeletion  include many malforma-

tion syndromes whose causative agent is obscure. A new method of using DNA probes and ﬂ  uorescence in situ hybridization has 
increased understanding of the causes of syndromes such as the Angelman, Cornelia de Lange, CATCH 22 ( cardiac defects, abnor-
mal face, thymic hypoplasia, cleft palate, and hypocalcaemia) 
(velocardiofacial syndrome), Miller–Dieker, Prader–Willi, Rubinstein–Taybi, Smith–Magenis, Sotos, Williams, and Wolf–Hirschhorn syndromes. Parental imprinting modiﬁ  es the expres-
sion of the genes involved in the Prader–Willi and Angelman 
syndromes.
(12, 14–16)
Subtelomeric deletions  or chromosomal rearrangements  have

Subtelomeric deletions  or chromosomal rearrangements  have 
been found in some persons with intellectual disability of hitherto unknown aetiology. Subtelomeric aberrations may explain up to 5 to 10 per cent of previously unknown causes.
(13,15)
Single-gene disorders  include states with intellectual disability 
in which the pedigree is highly suggestive of a single-gene origin. Some are caused by a mutant gene with simple Mendelian inheri-tance. Single-gene mutations may increase or diminish in frequen-cy in areas with long-standing populations of the same origin, or in populations isolated by language or culture. For example, the so-called Finnish disease heritage  includes 36 disorders, from which 
10 manifest with central nervous symptoms and some others may have them.
(17) Most of the speciﬁ  c disorders due to mutant gene

(17) Most of the speciﬁ  c disorders due to mutant gene 
have characteristic clinical phenotypic features, but there are a considerable number of non-syndromic individuals, especially in early infancy.
(12,18,19)
Autosomal dominant inheritance  causes tuberous sclerosis, 
myotonic dystrophy, Gorlin syndrome, neuroﬁ  bromatosis I, Apert 
syndrome, Menkes syndrome, and Huntington’s disease.
Autosomal recessive inheritance  is the cause of most metabolic 
diseases with intellectual disability. These diseases include phenylketonuria, homocystinuria, maple syrup urine disease, aspartylglucosaminuria, mannosidosis, Salla disease, I-cell disease, mucopolysaccharidoses (except type II), neuronal ceroid lipofusci-noses, Tay–Sachs disease, metachromatic leucodystrophy, Smith-Lemli–Opitz syndrome, and Joubert syndrome.
X-linked inherited disorders  include the fragile X, Aicardi,

X-linked inherited disorders  include the fragile X, Aicardi, 
Lesch–Nyhan, Lowe, Norrie, and Cofﬁ  n–Lowry syndromes, muco-
polysaccharidosis II, Duchenne muscular dystrophy, α-thalassaemia
intellectual disability syndrome, and Rett syndrome. The most Table 10.3.1 Aetiology based on the time and mechanism of 
the injury to the central nervous system and the history helping 
identiﬁ  cation, timing, and diagnosis of intellectual disability
Aetiology Historya
Genetic causes
Chromosomal disorders
Malformations due to
 microdeletionSingle-gene disorders
Multifactorial intellectual
 disabilityMitochondrial disordersFamily history
Family tree, intellectual disability,
 learning disabilities, neurological
 diseases, congenital anomalies, psychoses, consanguinity of
 parents, recurrent abortions,
 previous stillbirths, low parity or infertility, and parental ages
CNS maformations of unknown origin
Isolated malformation or
 malformation sequence of  the CNS

parents, recurrent abortions,
Multiple malformationsFamily and gestational history
External prenatal factors
Physical, chemical, and toxic agents
Maternal and gestational disorders
Other Gestational history
Maternal infections of the TORCH group, HIV, radiation, trauma,
 chronic maternal diseases, drugs,
 pre-eclampsia, severe malnutrition,
 alcohol, bleeding, and abnormal
 intrauterine growth or fetal movements
Paranatally acquired disorders
Delivery problemsOther newborn complicationsBirth and neonatal history
Gestational age, multiple pregnancy, 
 birth order, placental abnormalities,  labour or delivery complications/
 mode and duration, asphyxia, 
 intracranial haemorrhage, trauma,  5-min Apgar scores, newborn 
 weight, length and head

birth order, placental abnormalities,  labour or delivery complications/
 weight, length and head 
 circumference, infections,  hypoglycaemia, hyperbilirubinaemia, 
 neurological problems, and weight 
 gain
Postnatally acquired disorders
Other damage to CNSPsychosocial problems
Psychoses without family historyChildhood history
Feeding and sleeping patterns, 
 nutrition, growth charts,  developmental milestones, 
 infections of CNS, head injuries, 
 submersions, metabolic and  endocrine disorders, vascular 
 accidents or thromboses of 
 cerebral veins, cerebral tumours.  toxic agents, and psychosocial 
 environment
Untraceable or unclassiﬁ  ed causes
Pure non-familialWith CNS symptoms
Not classiﬁ  edHistory of associating conditions
No history of adverse events or signs  or history with CNS symptoms 
 such as cerebral palsy, epilepsy, or

 such as cerebral palsy, epilepsy, or 
 autism in addition to mental  retardation
CNS, central nervous system; TORCH, toxoplasmosis–other infection–rubella–
cytomegalovirus–herpes.
aGives the time of the risk event or cause, or appearing time of the sign whose cause(s) 
may also be earlier.10.3 aetiology of intellectual disability: general issues and prevention

SECTION 10  intellectual disability (mental retardation) 1832
common intellectual disability syndrome caused by mutation of a 
single gene is fragile X syndrome. The pattern of its inheritance is X-linked dominant with decreased penetrance.
(17,19,20)  The pre-
valence of the 24 other genes identiﬁ  ed to date in the X chromo-
some is low.(20) Dystrophic myotony, fragile X syndrome, and 
Huntington’s disease are caused by so-called dynamic mutation  in 
which the length of the repeated sequence of three DNA bases can vary from generation to generation increasing the variability in the phenotype.
(21) In Rett syndrome female inactivation of X chro-
mosome may be skewed. It explains the existing of the syndrome in a male or the very mild phenotype in a female.
(22) Epigenetic 
regulatory factors are also involved in the aetiology of Rett syndrome.
(23)
Mitochondrial disorders  are inherited in most cases due 
to mutations in the nuclear genes  encoding proteins targeted to

(23)
to mutations in the nuclear genes  encoding proteins targeted to 
this organelle. Autosomal dominant, recessive, or X-linked inheri-tances are possible. In addition, mitochondrial dysfunction is shown among others in patients with fragile-X, Rett, and Wolf–Hirschhorn syndromes or autism. 
(24–27)Mitochondrial 
DNA  (mtDNA) is inherited maternally. Sporadic deletions and 
duplications are also found (Kearns–Sayre syndrome, sporadic deletion or partial duplication in mtDNA). Examples of the mater-nally inherited (mtDNA) syndromes with central nervous symp-toms are the MELAS (mitochondrial myopathy, encephalomyopa-thy, lactic acidosis, and stroke-like episodes), MERRF (myoclonus epilepsy with ragged red ﬁ  bres), and NARP (neurogenic muscle

weakness, ataxia, retinitis pigmentosa), FSFD (facio-scapulo-femoral muscular dystrophy, familial cerebellar ataxia, recurrent Reye syndrome, cerebral palsy with intellectual disability), and cytochrome c oxidase (COX) deficiency (deafness, myoclonic epilepsy, ataxia, and intellectual disability ) syndromes. Nuclear 
genes are often involved in mitochondrial DNA depletion and 
Leigh syndromes, which are severe progressive diseases in early childhood.
(11, 18, 21)
Multifactorial  intellectual disability may be a state of pure famil-
ial intellectual disability or associated to some multifactorially 
inherited  conditions, for example neural-tube defects. One or more 
ﬁ rst-degree relatives are also affected. Similar pervasive develop-
mental disorders or childhood or other psychoses in one or more of ﬁ rst-degree relatives or otherwise strong family background 
suggest a polygenic component of intellectual disability.
(12, 21)
(b) Central nervous system malformations of unknown origin

(12, 21)
Approximately 30 to 40 per cent of all malformations are genetic
and 10 per cent have exogenous  causes. The aetiology of the rest is 
unknown. The number included in this aetiological group decreases with more accurate diagnosis of genetic malformations, intrauter-ine infections, other teratogenic agents, or deﬁ  ciencies of essential 
ingredients needed for the normal development.
(28,29)  The devel-
opment of the central nervous system may be disturbed at the following stages
(2,12,21,28,29):
1 dorsal induction at the 3rd to 7th weeks of gestation, leading to 
anencephaly, encephalocele, meningomyelocele, or other neural-tube-closure defects;
2 ventral induction at the 5th to 6th weeks of gestation, causing 
prosencephalies and other faciotelencephalic malformations;
3 proliferation of the neurones at the 2nd to 4th month of gesta-

tion, leading to microcephaly or macrocephaly;4 migration of the neurones at the 3rd to 5th month of gestation, 
causing gyrus anomalies and heterotopias;
5 organization of neurones from the 6th month of gestation to a 
year postpartum, leading to disturbances in the formation of dendrites and synapses;
6 myelination from 6th month of gestation to a year postpartum, 
disturbing the proliferation of oligodendrocytes and the forma-tion of the myelin sheets.
The malformation sequence  is a type of multiple malformation, 
which includes secondary anomalies caused by an earlier anomaly, for example equinovarus with meningomyelocele. Multiple 
malformation syndromes  are caused by the disturbances in blas-

togenesis or organogenesis. Multiple malformation syndromes of unknown origin include some whose causes are unknown such as the Goldenhar and Kabuki syndromes, and research will show that some of these aetiologically unknown syndromes have a genetic cause.
(30,31)
(c) External prenatal factors
The nature of the impairments or malformations, and the severity of resulting intellectual disability appear to relate, at least partially, to the timing of the causative factor as discussed earlier. Also dos-age may be important. Effects are most serious when the cause acts early in embryonic development ; during blastogenesis or organ-
ogenesis, when it may result in multiple malformations . Effects on 
the central nervous system of causes acting later  may be severe even

the central nervous system of causes acting later  may be severe even 
though outward signs may be lacking. These causes include con-genital infections such as rubella, cytomegalovirus, herpes simplex type 2, parvovirus, and HIV infection, as well as toxoplasmosis and syphilis. Exposure to medication and other substances such as hydantoin, lipid solvents, alcohol, cocaine, and other drugs can affect the developing foetus.
(2,3,28,32,33)
Maternal disorders  that may contribute to the causes of intellec-
tual disability include maternal diabetes, arterial hypertension, placental insufficiency, pre-eclampsia, pre- and postmaturity, multiple pregnancy, and foetal growth retardation. In other cases no speciﬁ  c causes can be identiﬁ  ed with certainty but available 
data strongly suggest a prenatal external cause of central nervous system impairment such as exposure to ionizing radiation or trauma.
(2, 34)

(2, 34)
(d) Disorders acquired in the paranatal period
The effects of the last week of pregnancy extend to the neonatal period and are very important for the outcome of the new-born,
(11,35)  and combinations of the prenatal and postnatal factors 
are not rare. Infections  are transmitted via placenta or the birth 
canal. They include neonatal septicaemia, pneumonia, meningitis, and encephalitis, which may lead by several mechanisms to neuro-logical deﬁ  cits, intellectual disability, and sometimes microcephaly, 
or in bacterial meningitides also to hydrocephalus. Congenital 
infections  of herpes simplex and HIV as well as tertiary syphilis 
may manifest later. Problems during delivery  may lead to asphyxia, 
intracranial haemorrhage, or other birth injuries and cause various symptoms of cerebral palsy and epilepsy. Other newborn

intracranial haemorrhage, or other birth injuries and cause various symptoms of cerebral palsy and epilepsy. Other newborn 
complications  include hypoglycaemia, hyperbilirubinaemia, 
and respiratory distress. Paranatal aetiologies may cause disorders of cognitive functions, as well as motor and sensory impairments.
(2,35,36)

1833
(e) Disorders acquired postnatally
Improved postnatal care has reduced the frequency of these causes, 
which include infections  such as meningitides and encephalitides.(37)
Other causes of postnatal damage to the central nervous system 
include toxic agents ,vascular accidents ,brain tumours ,hypoxia ,
and traumas . Trafﬁ  c accidents, other traumas, submersions, and 
cerebral tumours are common causes of disability in childhood. Lead poisoning has been a problem in the United States, iodine deﬁ ciency in some regions of the world, and malnutrition almost 
(38)Psychosocial problems  causing intellectual disability 
are not as common as was thought in the past, partly because of better identiﬁ  cation of medical factors.
(39) Severe maternal 
mental or chronic physical illness, parental alcohol or drug abuse, and some consequences of poverty may be contributory causes leading to inadequate care and stimulation. Deprived environments

are linked to other risks such as malnutrition, poor medical care, child abuse, usage of alcohol and other substances, and teenage pregnancies.
(40)
(f) Untraceable or unclassiﬁ  ed causes
The aetiology of intellectual disability can be classiﬁ  ed as unknown 
if the causative factor or timing of the brain damage cannot be established. Pure non-familial  intellectual disability is the term 
used when there is no family history of intellectual disability and no signs and symptoms suggesting brain damage. It represents the extreme of normal variation. In the untraceable group, the second category is intellectual disability of unknown aetiology  with other

symptoms and signs of the central nervous system suggesting brain damage, but with no family history of intellectual disability and no identiﬁ  ed malformations or dysmorphic features (see Table 10.3.1). 
Common examples are intellectual disability associated with cere-bral palsy, epilepsy, or autism. Patients should not be assigned to the untraceable group if the diagnostic work-up is incomplete.
(11)
If so, the aetiology is still unclassiﬁ  ed.
How to assess causes
A comprehensive history  and a careful physical examination  are 
essential for identifying and timing the causative factor(s). In everyday practice it is appropriate to assess the family history, embryological, and postnatal development, possible pathogenetic mechanisms, and the time of the exposure to the supposed agent (Table 10.3.1). The ﬁ  nding of more than three minor malformations
suggests genetic or early developmental disorder provided that the same dysmorphic features are not found in close relatives.
(41)

(41)
Infants at risk for external prenatal causes, perinatal causes, or postnatally acquired disorders should be examined carefully for dysmorphic features which may indicate alternative or additional cause. The diagnosis usually becomes evident by working out the history and clinical signs. Databases for analyses of dysmorphology ,
symptoms, or other ﬁ  ndings are useful aids in the search of an aeti-
ological diagnosis.
(42,43)
Ophthalmological and audiological examinations  can be arranged 
and other necessary investigations carried out when suggested by the history and physical examination (Table 10.3.2).
(2,4,11,12,18,21,37,38,41–43)
If the ﬁ  ndings are in accordance with history  and a person has no con-

genital anomalies, further examinations are seldom needed. However, the possibility of a metabolic disorder should be kept in mind, espe-cially as congenital anomalies or dysmorphic features may occur in people with metabolic disorders. Metabolic studies  should be performed for every patient with progressive symptoms .If the history 
and physical ﬁ  ndings do not match , or if there are congenital anomalies 
or more than three minor dysmorphic features, additional studies are needed.
(41) Because more accurate diagnostic methods are being 
developed, it is useful to keep for each person a dated chart of examina-
tions  performed.(11)
Prenatal diagnosis  may be indicated when there is a known

Prenatal diagnosis  may be indicated when there is a known 
parental balanced translocation, chromosomal aberration of a sibling, a known hereditable disorder in family, a multifactorial disorder such as neural-tube defect in the family, or the mother is elderly.
The gravidity can be detected by ultrasound examination  at 
6th to 8th gestation weeks. Many structural changes can be found from 11th to 15th weeks and conﬁ  rmed by repeated examinations 
to 22nd gestation week, for example neural-tube defects. The nuchal translucency in relation to crown-rump length and gestation week  can be measured during the 9th and 14th for detecting 
Down syndrome. Other general screening methods for Down syndrome are based on the applicable markers from the serum of the 
mother  to the 10th to 14th and 15th to 18th gestation weeks.
(44,45)

(44,45)
According to the positive screening result or abnormal morphology 
ﬁ nding in the ultrasound examination foetal karyotype or some 
other further examination may be indicated. The age-speciﬁ  c 
screening of foetal chromosomes is based on the signiﬁ  cantly 
increased probability of a Down syndrome child among mothers aged 35 years or older.
(12)
The karyotype of a foetus  can be identiﬁ  ed after the 10th week of 
gestation from a chorionic villus sample , or after 15th week gesta-
tion from the cells of amniotic ﬂ  uid. A known single-gene disorder 
can also be searched from the chorionic villus sample by DNA ,
Table 10.3.2 Diagnostic examinations of intellectual disability
◆  Neurological, ophthalmological, audiological, cardiological, 
neuropsychological, etc., assessments

◆ Blood count, vacuolated lymphocytes, and thyroid function
◆ Antibodies, serology, and urine (TORCH, HIV)
◆  Radiographs of skull, vertebral column, chest, hands, feet, and long bones, and bone age
◆ Chromosomes: G-banding, high-resolution banding, and FISH array CGH
◆ FraX DNA, speciﬁ  c DNA tests, and other molecular genetic techniques
◆  Blood/urine: amino and organic acids, muchopolysaccharides, oligosaccharides, long- and very-long-chain fatty acids, Astrup, glucose, 
ammonia, lactate, pyruvate, uric acid, phytanic acid, carnitine, lead, copper, 
ceruloplasmin
◆ Fibroblast culture or white blood cell sample; speciﬁ  c enzymes
◆ Biopsies: muscle, skin, rectal
◆ Neurophysiological: EEG and evoked potentials
◆  Neuroimaging: cranial ultrasound, CT, MRI, MRS, functional MRI, SPECT, and PET

◆ Neuropathological examinations
TORCH, toxoplasmosis–other infection–rubella–cytomegalovirus–herpes; FISH, 
ﬂ  uorescence in situ hybridization; MRI, magnetic resonance imaging; SPECT, single-photon emission CT; PET, positron emission tomography; MRS, magnetic resonance spectroscopy.10.3 aetiology of intellectual disability: general issues and prevention

SECTION 10  intellectual disability (mental retardation) 1834
enzyme ,or other speciﬁ  c methods . Cell cultures of few amniotic ﬂ  uid 
cells can be used for karyotyping or diagnosing metabolic diseases, 
but it needs more time. Neural-tube defects, also the small ones, can be seen as elevated levels of α-fetoprotein  in amniotic ﬂ  uid. 
Sometimes a blood sample from the umbilical cord is needed after 
the 18th gestation week for conﬁ  rmation of karyotype.
Prenatal diagnostic methods and identiﬁ  cation of parental bal-
anced translocations or aberrations in single gene are increasingly available. Microarray-based comparative genomic hybridization 
(array CGH), examination of foetal DNA or cells derived from maternal blood circulation, and preimplantation diagnoses becom-
ing available for some diseases will change the prenatal diagnosing practice considerably.
(12,21,46,47)
Why knowledge of causation is important

Intellectual disability is a confusing concept . The people with intel-
lectual disabilities have more differences than common features. Developmental delay may appear in different ages and with differ-ent degrees of severity in different children. The development of a child can come to a stop or can even regress. There is a multitude of conﬁ  rmed causes of intellectual disability. Single aetiologies are 
rare and the clinical picture within the same aetiology and between different aetiologies can vary greatly. It is now possible to detect causes that until recently were unknown. Associated disabilities and chronic diseases are common and modify further the complex interplay of individual and environmental factors.
The factors believed to be related to the incidence and prevalence

The factors believed to be related to the incidence and prevalence 
of intellectual disability, such as personal history and gender, the age and the marital status of the parents, the number of siblings, 
and the living conditions and the social situation of the family, 
as well as the neighbouring community, vary in persons with intel-lectual disability. Attitudes to disabilities  may differ in different 
families and societies. The permanence of the cognitive impair-ment is difﬁ  cult to accept. Insufﬁ  cient or inadequate information 
or a prolonged diagnostic process may lead the family or the child to become fearful about the cause of the condition or to try and identify some reason for it. The way is then open for misunder-standings, feelings of guilt, or projections.
(4,11,48)
For the person with intellectual disability  a conﬁ  rmed aetiology is

(4,11,48)
For the person with intellectual disability  a conﬁ  rmed aetiology is 
the basis of a correct awareness of his or her own disability; the limitations set by the disability and the possibilities for learning and development. The clinical manifestations of some develop-mental disorders, such as phenylketonuria, galactosaemia, or hypo-thyroidism can be prevented or arrested by dietary management or hormonal replacement therapy. Knowledge of the prognosis increases awareness of associated disease and disabilities such as sensory impairments, communication disorders, motor and joint problems, epilepsy, and behavioural or psychiatric problems. Thus, aetiology aids the planning of follow-up, rehabilitation, education, and living arrangements.
(4,11) Knowledge of aetiology is particu-
larly important at the time of transition from childhood to adult services, helping to ensure continuity of provision and to avoid drop-out.

For the family , knowledge of causes helps to dispel wrong beliefs, 
self-blame, and anxieties. The parents and siblings may change their preconceived ideas about the disability. It helps the parents to adopt appropriate standards for bringing up their child, and for life as an adult. It helps them to become aware of the child’s special needs.
(4,11) Aetiologic diagnosis is the necessary basis of reliable 
genetic counselling and helps the parents and siblings in family 
planning.(12,48)
In society  the knowledge of the aetiologies of intellectual disability

In society  the knowledge of the aetiologies of intellectual disability 
increases the likelihood that its people will adopt positive attitudes towards the disabled. Both the society and its service providers need understanding of the causes of intellectual disability, their prevalence, and their prognoses when planning primary preven-tion, organizing services and education, optimizing environmental factors, or preparing relevant legislation. Society needs experts continuously alert to advances in scientiﬁ  c research to keep this 
knowledge up to date.
When the causes are unknown , prognosis is uncertain and the 
planning and provision of the services is difﬁ  cult. The risks of dis-

continuities in service provision and of drop-outs increase. Because families have limited information they are more likely to develop wrong beliefs, self-blame, and projections. They have unrealistic expectations about alternative therapies.
(12, 48)
The identiﬁ  cation of factors that contribute to intellectual disability, 
their removal or avoidance, and the protection of the population or individuals against them  are the main principles of primary preven-
tion. Immunization and other measures to prevent rhesus incom-patibility, congenital rubella, measles encephalitis, tuberculosis and other bacterial meningitides, prionic diseases, and the provision of folic acid around the time of conception to prevent neural-tube defects have been successful preventive measures.
(2,37)

(2,37)
Primary prevention includes good medical follow-up ,the identiﬁ  -
cation and prompt removal of ,or effective intervention in , at-risk 
situations during pregnancy, delivery, the neonatal period, and 
childhood. Avoidable causes include intrauterine and perinatal infections due to many sexually transmitted diseases, and fetal 
alcohol spectrum disorders (FASD).
(49) Lead intoxication, iodine 
deﬁ ciency, accidents in the home, and trafﬁ  c accidents are prevent-
able.(2,36,38)  The primary prevention of genetic disorders has not 
been possible, although the disorder, the chromosomal aberration, or some associated abnormality can sometimes be identi-ﬁ ed.
(21,29,44)  However, all the means of the secondary prevention 
are available, and pregnancies may be terminated after counselling. Screening tests can identify some parents who are carriers.
(48) The 
preimplantation diagnosis could give a new way for the early pre-vention of known genetic disorders in some cases.
(47,50)

(48) The 
(47,50)
Early recognition and diagnosis ,good medical care ,and rehabilita-
tion of injuries or diseases  can avoid or reduce permanent damage 
which could lead to intellectual disability. Examples include the screening for and early treatment of congenital hypothyroidism and phenylketonuria.
(2) Secondary prevention also includes plan-
ning or genetic counselling  after the birth of a child with a genetic 
disorder.(48) The examination of asymptomatic parents and close 
relatives in order to detect carriers is part of genetic counselling. As yet there are no measures to prevent the underlying biological processes in genetic disorders.
(12,18,21)
Once children with intellectual disability have been identiﬁ  ed, 
accurate assessment of aetiology and associated conditions, therapy,

1835
and rehabilitation lessen the risk of so-called caused learning 
disability , that is leaving the person with intellectual disability 
without the possibility of developing further because he or she is unable to share in the learning experiences of the peer group.
(2,4,38)
The aim of tertiary prevention is to help an individual attain his or 
her full developmental potential.  Therefore tertiary prevention part-
ly overlaps with secondary prevention. It encompasses all measures, which prevent or lessen persistent hindrances to the development of functional ability or social competence in people with identiﬁ  ed

damage or disease. It includes medical, psychological, social, and family support, environmental adjustments, aids, and education. In the ideal state, individual supports are so good that the mentally retarded can live a life similar to that of people without intellectual disability. However, even when this can be achieved, problems may reappear when tasks of life increase, or the supporting systems fail.
(4,10)
Ethical problems of prevention
Usually there are no ethical problems . There are hardly any issues 
surrounding the prevention of causative diseases or injury, the attempt to reduce the prevalence of inheritable diseases by family planning or genetic counselling, the screening that leads to the treatment of the foetus or the newborn, preparation for the birth 
of a new infant, improving the care and rehabilitation, and plan-ning a safer society.
Ethical questions arise if there are no measures to prevent  the effects

Ethical questions arise if there are no measures to prevent  the effects 
of an identiﬁ  ed genetic or other cause of intellectual disability 
identiﬁ  ed during pregnancy. Disordered genes, other genetic rear-
rangements, or accidental mutations cannot be removed from a population. Primary prevention of an intellectual disability becomes the prevention of childbirth or selective abortion. The latter is usually on the grounds that the burden of caring for the child would be too great for the parents, an indication that is more social than medical.
(51,52) In general, the prevention of a disease 
does not exclude good therapy for it. However, the increasing trend to accept selective means of prevention may be a result of cultural change and increasingly negative attitudes towards disability.
(53–56)
Prenatal diagnosis , detection of carriers and screening for disor-

(53–56)
ders, which cannot be prevented or treated, usually lead to deci-sions about more or less harmful consequences. Ethical questions include choices between knowing and not knowing , between not 
knowing and worry or anxiety in risk situations, and between the need to take difﬁ  cult decisions and to avoid them. It is very difﬁ  cult 
to predict accurately all the long-term effects of these decisions. Parents have the right to be able to make voluntary decisions, but they need accurate information  to be able to bear the burden of 
responsibility.
(51,56–58)
Prevention requires a coordinated programme
On the basis of the aetiologies deﬁ  ned according to the timing

On the basis of the aetiologies deﬁ  ned according to the timing 
principle, it is possible to search for epidemiological, psychological, sociological, and other explanations to answer the question ofwhy some causes are more common in certain populations orsubgroups than in others. The starting point of prevention is knowl-
edge of causation  and identiﬁ  cation of factors that subject individ-
uals to these causes. With better understanding of the causes of intellectual disability, attitudes towards it change. With knowledge, 
individuals needing support can be identiﬁ  ed earlier, their devel-
opment and life made easier, and the burden of care on the family lightened.
Public policy, education, public health, obstetric services, neona-
tal intensive care, general practice services, etc. have an important 
role in reducing and avoiding risk factors. Education, planning of

role in reducing and avoiding risk factors. Education, planning of 
a safe environment and alleviation of poverty has a general preven-tive effect on predisposing factors. The preventive aspects should be 
taken into account in all general and speciﬁ  c legislation ,in operating 
procedures ,and professional practice . Because multiple agencies are 
involved preventive measures need to be coordinated at both local and national levels.
The day-to-day prevention of infections, accidents in the home 
and trafﬁ  c, exposure to toxic substances, drowning accidents, 
malnutrition, or child abuse is both a general and a multiprofes-
sional task . Parents and educators should transfer their wisdom and 
experience to the next generation so that they will make better choices and avoid risks.
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1837
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10.4
Syndromes causing 
Psychiatrists working with people who have intellectual disability 
(mental retardation) need expertise in the diagnosis and treatment of associated neuropsychiatric disorders. This entails knowledge of the causes of intellectual disability, and especially knowledge about those syndromal (often genetic) causes that are associated with neuropsychiatric manifestations. Such manifestations include vul-nerability to behavioural and emotional disorders, epilepsy, and particular patterns of cognitive strength and weakness. This chap-ter provides an introduction to some such disorders and a discus-sion of the concept of behavioural phenotypes. For a detailed account of conditions causing intellectual disability texts such as Jones
(1) should be consulted. The concept of behavioural pheno-
types is discussed in detail in O’Brien.(2)
The genetic aetiologies of intellectual disability include chromo-

somal abnormalities (trisomy, deletion, translocation, etc), single-gene defects, and the effect of interactions between several genes. The last is thought to account for a substantial proportion of peo-ple with mild intellectual disability by setting a ceiling on possible cognitive attainment (life experiences, nutrition, education, and other factors then determining the extent to which potential is ful-ﬁ lled or thwarted).
This chapter discusses the concepts of syndromes and behav-
ioural phenotypes, then describes the clinical features of a number of syndromes that cause intellectual disability. Down syndrome, fragile-X syndrome, sex chromosome anomalies, and foetal alcohol syndrome are described in some detail. This is followed by a briefer alphabetical list of less common conditions.
Syndromes

Syndromes
A syndrome is a characteristic pattern of clinical features, including signs (that can be observed) and symptoms a patient may experi-ence. They may be causes of intellectual disability (Down syndrome), associated with intellectual disability (syndromes of epilepsy, such as West syndrome), or coincidental (polycystic ovary syndrome). This chapter deals with some of the syndromes that increase vulnerability to intellectual disability. The vulnerability may be increased so much that all affected people have intellectual disability (Angelman 
syndrome) or increased to the extent that many, but not all, have 
intellectual disability (velo-cardio-facial syndrome).There can be disadvantages to the labelling of people with disab ility, 
but the identiﬁ  cation of a syndromal cause may have beneﬁ  ts for 
the affected person and for their families and carers. Beneﬁ  ts

the affected person and for their families and carers. Beneﬁ  ts 
include an explanation of the cause of the person’s disabilities or of unusual cognitive strengths and weaknesses, better understanding of risk of recurrence of the disorder among relatives, and the iden-tiﬁ cation of complications or associated features.
Identiﬁ  cation of a syndromal cause may give access to support 
organizations. A list of such organizations is given in the CaF (Contact a Family) Directory (www.cafamily.org.uk).
Behavioural phenotypes

Behavioural, social, linguistic, or cognitive aspects of a syndrome may be so striking and characteristic as to prompt diagnosis. Examples include the severe self-injury associated with Lesch–Nyhan syndrome and the combination of appetite abnormality, ritualistic behaviours, sleep abnormalities, skin-picking, repetitive speech, and vulnerability to psychiatric disorder associated with Prader–Willi syndrome. Such patterns of vulnerability to particu-lar emotional or behavioural problems or peculiarities associated with biologically determined syndromes have been called behav-ioural phenotypes. Environmental factors may interact with a genetically determined vulnerability to a behaviour to determine whether or not it occurs in a given setting. Knowledge of the nature of this interaction may be important in order to determine effec-tive treatment or management strategies. In Lesch–Nyhan disease, 
for example, all affected men self-injure, but whether a man with

for example, all affected men self-injure, but whether a man with 
the syndrome injures himself at a particular time is inﬂ  uenced by 
environmental and internal psychological factors such as anxiety. A careful assessment of the causes and consequences of behavioural problems is essential before interventions are planned, particularly the use of psychotropic medication to inﬂ  uence behaviour.
(3)
Speciﬁ  c conditions
Down syndrome
(a) Prevalence and genetics
J. Langdon Down originally described the syndrome in 1887. 
Trisomy 21 is associated with Down syndrome, and was ﬁ  rst 
reported by Lejeune and colleagues in 1958. About 1 in 600 live

1839
born children have Down syndrome. The rate increases with 
increasing maternal age, being about 1 in 2000 at maternal age 20 years and 1 in 100 at maternal age of 40 years.
(4) There are three

(4) There are three 
types of abnormalities affecting chromosome 21. In about 94 per cent of cases, Down syndrome is caused by primary non-disjunction leading to trisomy 21. The risk of recurrence of this abnormality is low if maternal age is also relatively low. In about 2 per cent of cases Down syndrome results from an unbalanced translocation (when material from one chromosome is separated and attached to another with some duplication). This often involves chromosomes 21 and 14. In some cases a parent also has a balanced translocation (with no overall disruption or duplication of genetic material), and this raises the risk of recurrence. Chromosome 21 to 21 transloca-tions can occur. Mosaicism occurs when there are two or more cell lines within the body. In Down syndrome there may be one cell line with trisomy 21 and one without. In about 2 per cent of cases the syndrome results from mosaicism. Some cases may not be diag nosed.

The proportion of affected and unaffected cell lines varies, as does the intellectual impairment.
(b) Physical characteristics
Muscular hypotonia at birth usually improves with development. Most adults are of short stature and have a characteristic facial appearance. The eyes seem to slope upwards and outwards, the nose has a wide bridge and the head has an unusual shape (brachy-cephaly). Limb abnormalities include a single transverse crease on the palm, a large cleft between the ﬁ  rst and second toes, and 
relatively short upper arms. People with Down syndrome are prone to thyroid abnormalities. About 25 per cent develop hypothyroid-ism during childhood or adolescence. About half of affected people have a heart abnormality. Abnormalities of the gastro-intestinal tract occur in a signiﬁ  cant minority. Life expectancy has improved

markedly over the past 50 years. Survival into the eighth decade is unusual but not extraordinary. Changes in blood cells are relatively common. Older texts reported an association between Down syn-drome and leukaemia, but recent r esearch suggests that leukaemia is 
rare, affecting less than 1 per cent of people with Down syndrome.
(c) Behavioural and psychiatric aspects
Adults with Down syndrome are much more likely to develop 
dementia than the general population. On post-mortem examina-tion, the brains of almost all adults with Down syndrome over the age of 35 show changes characteristic of dementia of Alzheimer type. Only about 38 per cent of those aged 50 to 59 have clinically apparent dementia, with a mean age at diagnosis around 51 years.
(5,6)
The stereotype of people with Down syndrome as happy, placid

(5,6)
The stereotype of people with Down syndrome as happy, placid 
individuals with a gift for mimicry is not borne out by recent behavioural research. Stubbornness and obsessional features seem to be over-represented, and many people with Down syndrome react adversely in situations involving changes to expected routines or conﬂ  ict. Autism seems to occur more commonly than would 
be expected, but few methodologically sound studies have been carried out.
(7)
Most adults with Down syndrome have moderate intellectual 
disability. Almost all children with Down syndrome have some degree of speciﬁ  c speech and language delay. About 25 per cent 
have features of attention-deﬁ  cit disorder. Cognitive abilities tend 
to be greater among people whose Down syndrome is caused by mosaicism for trisomy 21.Further information: www.downs-syndrome.org.uk
X-linked intellectual disability
The prevalence of X-linked intellectual disability is around 0.18 per

The prevalence of X-linked intellectual disability is around 0.18 per 
cent.(8) The majority of affected men have non-syndromic X-linked 
intellectual disability (usually referred to as X-linked mental retar-dation or XLMR in international literature), with no associated dysmorphology. The most common syndrome resulting in XLMR is fragile-X syndrome (described below). Cofﬁ  n–Lowry syndrome 
(CLS) is also described below. It is increasingly accepted that there is a spectrum of disorders associated with XLMR genes, ranging from deﬁ  ned syndromes such as CLS to XLMR with no dysmor-
phology. For example, the gene RSK2 is usually mutated in Cofﬁ  n–
Lowry syndrome but a missense mutation in exon 14 of RSK2 has been found in a family in which males have intellectual disability but no associated features of CLS.
(9) An interesting article described

(9) An interesting article described 
a woman with mild intellectual disability, epilepsy, and some minor dysmorphology whose karyotype was reported as normal in 1993. Repeated testing was carried out after she was found to have a more severely affected brother with a duplication affecting his X chromosome showed 46,X dup (X)(p22.13p22.31). The authors concluded that genetic testing for individuals with intellectual disability should be considered even when there was a low index of suspicion for an X-linked disorder.
(10) About 200 XLMR condi-
tions and 45 cloned genes have now been described.(11) At least 
eight genes have so far been implicated in non-speciﬁ  c XLMR: 
Rab-GDI ,PAK3 ,AGTR2 ,TM4SF2 , FRAXE ( FMR2 ), ARHGEF6 /
αPIX, and FACL4 .(12) Readers are referred to specialized texts 
such as Jaquemont et al. (2005)(12) and web resources such as xlmr.
interfree.it/home for further details.
Fragile-X syndrome

The syndrome was ﬁ  rst described in 1943. All ethnic groups are 
affected equally, with a frequency of about 0.3 per 1000 in men. More recent investigations with modern diagnostic techniques show lower ﬁ  gures than earlier studies.
(13)
Fragile-X syndrome is an X-linked disorder with a very unusual

(13)
Fragile-X syndrome is an X-linked disorder with a very unusual 
pattern of inheritance. It is characterized by a bias to affected men but with some affected women and some unaffected men who have daughters who then have affected sons. When peripheral blood lymphocytes from affected individuals are grown in certain culture conditions, including a lack of folic acid, a fragile site becomes evident on the long (q) arm of the X chromosome at Xq27.3 (fragile site A). Fragile sites may not be seen in some unaffected men who transmit the abnormality to their carrier daughters. These men were historically termed ‘normal transmitting males’ . The probabil-ity that a child with a fragile-X chromosome will have intellectual disability depends on the sex of the parent from whom the chromosome was inherited (higher risk when the chromosome is passed from the mother). The ‘fragility’ of the X chromosome is 
now known to be associated with an unstable region of DNA with-

in the fragile-X mental retardation (FMR-1) gene, which was ﬁ  rst 
described in 1991.
(14) This region of unstable DNA gradually 
increases in length and degree of instability in successive genera-tions (a pre-mutation) until a critical point is reached and the gene no longer functions (a full mutation). The instability is caused by an increase in CGG (cytosine-guanine-guanine) repeats from the 50 or so repeats that are usual to 50–100 repeats (pre-mutation) 10.4 syndromes causing intellectual disability

SECTION 10  intellectual disability (mental retardation) 1840
to over 230 repeats (full mutation). The chance of a child inherit-
ing a lengthened gene is proportional to the length of the unstable region in the carrier mother. The severity of intellectual disability and other fragile-X related phenomena in women probably depends mostly on the proportion of cells in which the abnormal chromo-some is inactivated, X inactivation being random. Most women who have children with fragile-X syndrome are premutation carriers of normal intelligence.
(15) Carriers of the premutation 
are intellectually unimpaired but are more vulnerable than other women to anxiety and depression.
(16) Variants of fragile-X syndrome 
have now been identiﬁ  ed, with DNA expansions nearer to the end 
of the long arm of the X chromosome. These include FraX-E and FraX-F.

Physical features are variable. The most characteristic feature is that about 95 per cent of affected men have large testes, although macro-orchidism is not usually apparent until after puberty. Other features include a long face with a large forehead, large ears, a large lower jaw, and high-arched palate. There is a connective tissue disorder that may lead to tissue laxity with hyper-extensible joints, ﬂ at feet, heart defects (especially valve abnormalities), and ear 
infections (the eustachian tube closes easily). Cataracts and other eye abnormalities may occur, and lead to impaired vision. About 30 per cent of affected men have epilepsy. Life expectancy depends on the severity of associated features such as epilepsy and cardio-vascular anomalies.

There is usually some degree of social impairment, with social anxiety and avoidance of eye-to-eye contact, but with social respon-siveness. Men with fragile-X are usually affectionate, and do not have the aloof quality typical of autism. Self-injury is relatively common, especially hand biting over the anatomical snuff-box (between the bases of the thumb and index ﬁ  nger) in response to 
frustration, anxiety, or excitement. Stereotyped behaviours such as hand ﬂ  apping are common.
The associated intellectual disability is usually mild to moderate. 
Verbal intelligence scores exceed performance scores among populations of affected men and non-disabled women carriers. Speech and language development is delayed. Speech is often disor-ganized, with rambling and circuitous conversation, incomplete sentences, poor topic maintenance, tangential comments, echola-lia, and perseveration. It may be rapid, or include peculiar changes 
in pitch.

in pitch.
There may be problems with attention and concentration that 
are disproportionate to the severity of the associated learning disability. Hyperactivity may be the presenting feature among boys with fragile-X who do not have intellectual disability.
Further information can be obtained from Hagerman and 
Hagerman (2002)
(17) and www.fragilex.org.uk.
Sex chromosome abnormalities
The Y chromosome is small and has been completely mapped.(18)
The X chromosome is much larger, containing over 1000 genes. Abnormalities of the X and Y chromosomes are more prevalent than those affecting autosomal chromosomes. Many affected children are not signiﬁ  cantly dysmorphic and do not have major 
developmental disabilities.
(19) Some remain undiagnosed.Klinefelter syndrome

This is a disorder characterized by additional X chromosomes in phenotypic males. Two-thirds have a 47 XXY chromosome com-plement. Prevalence at birth is about 1 in 1000 live males, with a frequency in prenatally karyotyped male foetuses of 1 in 470.
(19)
Height, weight, and head circumference are below average at birth. Increased growth, especially of legs occurs from 3 years of age onwards. Affected men are usually taller than their fathers, and mean heights are around the 75th centile. Head size remains small. Puberty normally occurs, but testosterone production falls in early adult life. Affected adults have a normal-sized penis but small testes. About 60 per cent have some breast enlargement. Life expec-tancy is thought to be normal.

Boys with XXY are typically introverted and less assertive and sociable than other children, with poorer school performance (especially with regard to reading and spelling). Adults may have increased rates of antisocial behaviour and impulsiveness. The IQ distribution is skewed downwards, although measured full scale IQs run from the 60s to the 130s. Performance scores usually exceed verbal scores. Most affected children receive speech and language therapy, and expressive language deﬁ  cits are often more 
pronounced than problems with receptive language. One follow-up study has been reported.
(20) Further information: www.
klinefeltersyndrome.org.
Turner syndrome

The genetic abnormality in Turner syndrome is the loss or abnor-mality of one X chromosome in women. The 45,X karyotype is found in about 1 in 10 000 live female births. The abnormality is much more common at conception. About 99 per cent of affected foetuses are miscarried, and 45,X is the most common karyotype found in chromosomally aborted foetuses. About 50 per cent have a 45,X chromosome complement (a very small proportion of nor-mal cell lines may be present). Most of the other cases are the result of mosaicism, some are the result of structural abnormalities of an X chromosome.

Affected children have a short stature in childhood. Ovarian failure occurs before birth, and puberty does not usually occur naturally, although childbirth has, rarely, been reported. Dysmorphic features include a webbed neck, low hairline at the rear of the head, widely spaced nipples and multiple pigmented naevi. About 12 per cent have coarctation of the aorta or a ventricular septal defect.
Hyperactivity and distractibility are common in childhood. Poor social skills, with immature social relationships and low self-esteem in adolescence were reported in one study.
(21) Women with Turner 
syndrome are usually of normal intelligence and verbal abilities are usually unimpaired or enhanced. Speciﬁ  c cognitive abnormalities 
including deﬁ  cits in spatial perception, visual motor integration, 
affect recognition, visual memory, and attention have been reported.

(22) The relative strength in verbal tasks may lead to an

1841
overestimation of abilities. There is considerable variation in cog-
nitive proﬁ  le between affected women. Further information: www.
tss.org.uk
XXX syndrome
(a) Genetics and prevalence
The 47,XXX syndrome occurs about 1 in 1000 female births.(23)
Many are not diagnosed. There is a primary non-disjunction of a maternal or paternal X chromosome. The 48, XXXX chro mosome
complement is much rarer (about 40 cases have been reported so far).
In 47,XXX syndrome newborn babies have a low birth weight and small head circumference. Height in adult life is usually increased, with a low body mass index. Fertility is not usually impaired, although there are reports of premature ovarian failure and recur-rent spontaneous abortion. There may be deﬁ  cits in balance or ﬁ  ne 
motor coordination. Life expectancy is thought to be normal.

Underactivity and withdrawal have been reported. Emotional development may be slowed. About a quarter of affected women in one follow-up study had repeated episodes of abdominal pain as teenagers for which no organic cause could be found.
(24) Most 
appear to adapt to adult life without difﬁ  culties. Women with the 
syndrome usually have IQs between 80 and 90. Women with XXXX 
syndrome have lower IQs (55 to 75). An expressive language delay is typical. Some have a relatively poor short-term auditory memory. Further information: www.triplo-x.org.
XYY syndrome
(a) Genetics, prevalence, and physical characteristics
This karyotype is associated with 1 in 1000 live male births.(23)

There is a primary non-disjunction of the Y chromosome. About 10 per cent have mosaic 46,XY/47,XYY chromosome complement. Offsprings rarely have two Y chromosomes. Affected individuals show increase in body and leg length between years 4 and 9. Most are over 10 cm taller than their fathers as adults. Sexual develop-ment and fertility are unaffected. Balance and coordination may be minimally compromised. Life expectancy is normal.
(b) Behavioural and psychiatric aspects
Early research found an increased frequency of XYY men among inmates of special prisons.
(25,26)  More recent studies examining

(25,26)  More recent studies examining 
the relationship between 47,XYY karyotype and behaviour have concluded that affected men have lower mean intelligence scores (with a large overlap with the normal range) and poorer social adaptation. Distractibility, hyperactivity, temper tantrums, and speech and language problems appear relatively common in childhood. There is little evidence to suggest a signiﬁ  cant link with 
seriously aggressive criminal conduct in adult life.
(27,28)
(a) Classiﬁ  cation and prevalence
Exposure of the developing foetus to significant amounts of 
alcohol leads to cognitive impairment. The effect can occur during any stage of pregnancy, because brain development continues during all three trimesters. Dysmorphology, including a facial dysmorphology, can also occur. Foetal alcohol spectrum disorder

(FASD) includes a number of subtypes including foetal alcohol 
syndrome (FAS), and more subtle abnormalities subsumed under 
the terms possible foetal alcohol effects (PFAE), prenatal exposure to alcohol (PEA), or alcohol-related neurodevelopmental disorder (ARND).
Foetal alcohol exposure is thought to be a common cause of 
intellectual disability in the United States and other developed countries. In the United States, an estimate of 0.33 per 1000 births has been given for the prevalence of foetal alcohol syndrome.
(29)
Alcohol inhibits N-methyl- d-aspartate receptors, which mediate 
postsynaptic excitatory effects of glutamate, and this is thought to have an effect on cell proliferation.
(30)
(b) Clinical features

(30)
A number of abnormalities have been linked to FAS. Facial dys-morphology commonly includes a thin upper lip and smooth phil-trum. The jaw may be small. Low-set abnormal ears and palate abnormalities can occur. Other abnormalities include growth retar-dation, skeletal abnormalities (deformed ribs and sternum, spinal curvature, dislocated hips, fused or webbed or missing ﬁ  ngers or 
toes, limited joint movement, small head), heart abnormalities, and urinary tract anomalies.
(c) Neurological and behavioural aspects

Central nervous system abnormalities include a small brain with abnormally arranged cells. Intellectual disability is usually mild or moderate but may be severe. Other problems commonly include reduction in attention span, overactivity, irritability in infancy; and coordination problems.
Angelman syndrome
The prevalence of this syndrome is around 1 in 10 000 births.(31)

Most cases are sporadic, and associated with deletions within 15q11q13 of maternal origin (Prader–Willi syndrome). Angelman syndrome is occasionally associated with paternal uniparental disomy (both chromosome 15s are of paternal origin) but this is less common than in Prader–Willi syndrome. Other genetic abnor-malities leading to Angleman syndrome are an imprinting centre defect (this incorrectly ‘marks’ the chromosome, through methyla-tion, as being from a parent of the opposite sex) and mutations in the gene responsible for the Angelman syndrome phenotype (UBE3A, coding for a ubiquitin ligase enzyme).
(32) UBE3A is 
expressed only from the maternal chromosome, and in Angelman syndrome expression in relevant brain areas is only around 10 per cent of normal.

Physical characteristics include a small head, characteristic face with wide mouth, ‘hooked’ nose, prominent lower jaw, widely spaced teeth, and tongue protrusion. Many affected children are hypopigmented compared to ﬁ  rst degree relatives due to deletion 
of a gene related to pigmentation.
(33) Voluntary movements are 
jerky and the gait ataxic with stiff legs. About 80 per cent develop epilepsy, and the EEG is highly characteristic.
Behavioural characteristics, including sudden bursts of laughter and the jerky ataxic gait, led to the term ‘happy puppet’ syndrome 10.4 syndromes causing intellectual disability

SECTION 10  intellectual disability (mental retardation) 1842
being used in the literature of the 1960s and 1970s. It is no longer 
considered appropriate. Affected children enjoy social and physical contact, and mouthing objects. Many are fascinated by water. Intellectual disability is severe, with markedly delayed motor mile-stones. There is little speech development (no person reported in the literature has more than a six word vocabulary), but under-standing of language may be better. Overactivity is often associated with a short attention span in childhood, but may improve with development. Behavioural studies have been reported
(34) and 
genetic aspects reviewed.(35) Further information: www.assert.dial.
pipex.com/
Cofﬁ  n–Lowry syndrome
Coffin–Lowry syndrome is one cause of X linked intellectual 
disability. The syndrome has been ascribed to a locus in the Xp22.1-p22.2 region. More than 100 cases have been reported.

Physical features include short stature, facial dysmorphology including slanting eye ﬁ  ssures, prominent forehead, short broad 
nose, forward facing nostrils, large ears, large mouth and small, widely spaced teeth. Increased fatty tissue is deposited in the fore-arms. Hands are often large, with tapering ﬁ  ngers. Ligament laxity 
may lead to flat feet. Spinal and chest abnormalities occur. Behavioural and emotional characteristics are largely unknown, although depression and schizophrenia have been reported in association with the disorder and in female carriers.
Affected men usually have severe learning disabilities. Drop attacks and sleep apnoea syndrome have been reported. Further information: www.clsf.info.

Following the introduction of a neonatal screening programme in the United Kingdom, the incidence of congenital hypothyroidism (identiﬁ  ed through heel-prick screening and further investigation 
for at risk infants) is about 1 in 4000, and occurs more commonly in girls. In many cases the deﬁ  ciency of thyroid hormones is mild, 
and there are few symptoms.
(b) Physical and cognitive characteristics

Severely affected children have a distinctive appearance with a puffy face and a large tongue that protrudes from a mouth that is kept open. Other features include dry, brittle hair, a low hair line, jaundice, sleep disorders, low muscle tone, constipation, and failure of cognitive development leading to intellectual disability. If untreated, even mild hypothyroidism may lead to intellectual disability.
Cri-du-Chat syndrome (CDCS, 5p-syndrome)
Cri-du-Chat syndrome was originally described as a syndrome of multiple congenital anomalies, intellectual disability, microcephaly, abnormal face, and a mewing cry in infants with deletion of a ‘B group chromosome’ , later identiﬁ  ed as a 5p terminal deletion.

The prevalence is about 1 in 35 000 births. Deletions vary in size, but the critical region for Cri-du-Chat syndrome is thought to be 5p15.2. About 85 per cent of the deletions arise spontaneously and 
the majority are of paternal origin. About 15 per cent of affected people have an unbalanced translocation, and the clinical features depend on the other chromosome involved. Fewer than 1 per cent of cases are due to inherited deletions, which are usually very small.
In infancy there are feeding difﬁ  culties and the cry is abnormally 
high pitched (cat-like, hence ‘cri-du-chat’), but this is not an invari-able feature. The gene causing the abnormal (cat-like) cry has been located at 15p13. It is possible for infants with small deletions to have a cat-like cry but no other features of CDCS, or features of CDCS without the characteristic cry. A round face with widely spaced slanting eyes, a small head, a broad ﬂ  at nose, and small

lower jaw are characteristic. Ear abnormalities may occur. Larger deletions, and some translocations, are associated with more pronounced clinical features such as lower intelligence, smaller stature, lower weight, and smaller head. The face often lengthens with development and may be asymmetrical. Cleft lip or palate, curved ﬁ  ngers, hernias, and orthopaedic abnormalities may occur. 
Older individuals often have premature greying of the hair.
Hyperactivity is a problem for a substantial proportion of children, but may improve with age.
(36) Language development is often 
markedly delayed. The IQ associated with the syndrome in one study varied from 6 to 85. Further information: www.criduchat.asn.au.
De Lange syndrome (Brachmann–de Lange syndrome)

This syndrome is considered to occur about once in 60 000 live births, although some authors believe it to be more common. Mutations in a large gene on chromosome 5, the Nipped B like or NIPBL  gene (named because its function resembles that of a fruit 
ﬂ y gene that produces a nipped wing), have been shown in about 
40 per cent of people with the syndrome.
(37)
Affected individuals show growth retardation; distinctive facial features consisting of well-deﬁ  ned arched eyebrows which meet in 
the middle, long curled eyelashes, small nose with forward-facing nostrils, and down-turned mouth with thin lips and limb abnor-malities such as small or shortened limbs, especially arms. Hearing impairments, gut malformations, and congenital heart defects also 
occur. Early mortality is high because of feeding problems with 
regurgitation and vomiting leading to aspiration pneumonia in

regurgitation and vomiting leading to aspiration pneumonia in 
some cases.
Self-injury, autistic features, and pleasurable responses to vestibular 
stimulation, e.g. spinning in a chair have been reported as part of behavioural repertoire. The degree of learning disability is usually severe, and speech is often very limited. However, some affected people have IQs within the normal range. Clinicians should be alert to the presence of pain and discomfort resulting from gastro-oesophageal reﬂ  ux and other gastro-intestinal abnormalities. 
Further information: www.cdlsusa.org.

1843
Duchenne muscular dystrophy
This is an X linked recessive condition in which deletions, duplica-
tions, and mutations at Xp21 lead to failure to produce dystrophin, a protein component of muscle tissue. New mutations account for about 30 per cent of cases. The prevalence at birth is about 1 in 
4000 male births.
The syndrome is characterized by progressive muscle weakness, 
affecting the pelvis, upper leg, and upper arm muscles ﬁ  rst. The 
onset is typically between 2 and 6 years of age. Respiratory muscles are involved later in the disease process. Heart muscle abnormali-ties may also occur. The disease is usually more severe in the lower limbs and trunk initially, with later involvement of the arms and respiratory muscles. Affected boys often need a wheelchair by around 11 years of age, with death in early adult life (typically in the mid twenties).

Low mood, anxiety, and social abnormalities are often problems, and may become more prominent as the disorder progresses. These features may be reactions to a chronic and progressive physical disease. Specific learning disabilities are common, especially speciﬁ  c reading disorder. About 25 per cent of those affected have 
a learning disability. Performance IQ is typically higher than verbal IQ. Further information: www.mda.org.au.
Lesch–Nyhan syndrome
This X-linked recessive disorder results from a deﬁ  ciency of a 
purine salvage enzyme, hypoxanthine-guanine phosphoribosyl transferase (HGPRT) leading to hyperuricaemia, and neurological disorder. Partial HGPRT deﬁ  ciency results in gout. HGPRT is a 217 
amino acid peptide coded for by one gene divided into nine exons, located on the X chromosome at Xq26q27. Many different genetic lesions can cause HGPRT deﬁ  ciency. Complete and partial deletions,

amino acid peptide coded for by one gene divided into nine exons, located on the X chromosome at Xq26q27. Many different genetic lesions can cause HGPRT deﬁ  ciency. Complete and partial deletions, 
insertions, and duplication of exons have been reported. Most lesions appear to be point mutations. Affected males may have had spontaneous mutations or inherited mutations from asymptomatic female carriers. Carrier detection and prenatal diagnosis are possible. The incidence is around 1 in 380 000 births.
(38)
Neurological features include athetoid and other abnormal move-ments and spasticity. Growth retardation is usual. The presentation is usually with hypotonia and motor delay at about 4 months. Extrapyramidal signs (such as spasticity and choreo-athetoid movements) develop at about 9 months. Hyper-reﬂ  exia and clonus

appear at about 1 year. Dystonic movements may also develop. Dysarthria is common. Affected individuals may survive to the sec-ond or third decade. Death is usually due to kidney failure secondary to uric acid deposition or infection. The syndrome is associated with abnormal neurotransmitter turnover in the basal ganglia.
Compulsive severe self-injury is very prevalent and usually consists 
of ﬁ nger and lip biting, with self-splinting in an attempt to prevent 
the behaviour.(39) Other compulsive behaviours occur; men with 
the syndrome are reported to hit, spit, and swear at caregivers while apologizing for their behaviour at the same time.(40) The mean age 
at onset of self-injury is 3.5 years, with wide variation. The IQ is usually between 40 and 80, but dysarthria and neurological prob-lems limit the validity of standard IQ tests. Further information: www.lndinfo.org.
Mucopolysaccharidoses
(a) Classiﬁ  cation, genetics, and prevalence

The mucopolysaccharide group of disorders have both names 
(Hunter syndrome, Hurler syndrome, Sanfillipo syndrome, Morquio syndrome, Schie syndrome, Maroteaux–Lamy syndrome, Sly syndrome) and numerical designations (MPS IIA/B, MPS IH, MPS IIIA/B/C/D, MPS IV A/B, MPS IS, MPSVI, MPSVII, respec-tively). The disorders result from deﬁ  ciencies in enzyme systems 
involved in the degradation of glycosaminoglycans leading to the accumulation of abnormal metabolic products. The prevalences among live born children are approximately 1 in100 000 for Hunter and Hurler syndromes, 1 in 200 000 for all types of Sanﬁ  llipo 
syndrome and for Morquio syndrome, and 1 in 500 000 for Schie syndrome. Hunter syndrome is much more prevalent in Israel. The transmission is autosomal recessive except in Hunter (IIA and IIB) which is X linked.

Physical features vary. Coarse facial features (‘gargoylism’), hepato-splenomegaly, joint stiffness, eye abnormalities, and short stature occur in many of the disorders. Life expectancy varies from death in the ﬁ  rst decade in Hurler syndrome through survival into 
second or third decade in Sanﬁ  llipo syndrome, to survival to adult 
life in Hunter syndrome and Schie syndrome.
Sleep problems and abnormal nocturnal behaviours such as staying up all night, night-time laughing and singing, sudden crying out, and chewing of bedclothes have been reported in association with Sanﬁ  llipo syndrome, and have been shown to respond to behav-

ioural management strategies. Other problem behaviours reported in association with MPS disorders include aggression, overactivity, restlessness, and anxiety. Cognitive abilities vary from normal intelligence in Schie syndrome to severe learning disability and progressive cognitive deterioration in Hurler syndrome. Sanﬁ  llipo 
syndrome is associated with slower progressive cognitive impair-ment than that seen in Hurler syndrome, but often with marked behavioural and psychiatric abnormalities consistent with the diagnosis of childhood disintegrative disorder. The susceptibility to tooth decay in Morquio syndrome can lead to pain and problem behaviours. Further information: www.mpssociety.org.
Neuroﬁ  bromatosis type 1
This autosomal dominant disorder was ﬁ  rst described by von

This autosomal dominant disorder was ﬁ  rst described by von 
Recklinghausen in 1882 and occurs about once in 3000 births. The gene responsible is localized to 17q11.2. The gene product, neuroﬁ  bromin, regulates cell division and is thought to suppress 
tumour formation. A high spontaneous mutation rate means that about a half of all cases of NF1 arise in unaffected families.
Tumours arise from the connective tissue of nerve sheaths. Two or more of the following features are usually required for diagnosis: 10.4 syndromes causing intellectual disability

SECTION 10  intellectual disability (mental retardation) 1844
six or more cafe au lait (light brown) skin lesions more than 5 mm 
in diameter before puberty or 15 mm after puberty, two or more neuroﬁ  bromas or one plexiform neuroﬁ  broma (tumours of the 
nerve sheath); freckling of the inguinal or axillary region; two or more lisch nodules (benign iris hamartomas); an optic nerve glioma (tumour); a bony lesion characteristic of neuroﬁ  bromatosis 
(usually shin bowing or scoliosis), a ﬁ  rst degree relative with 
the disorder. About 45 per cent of affected people will have non-enhancing hyperintensities (or unidentiﬁ  ed bright objects ‘UBOs’) 
on magnetic resonance imaging. These are commonly seen in the cerebellum, basal ganglia, brain stem, and thalamus.
(41)
About 50 per cent of children have speech or language abnormalit ies.

(41)
About 50 per cent of children have speech or language abnormalit ies. 
Distractibility and impulsiveness may be problems. Learning disability is present in about 10 per cent of affected people. Speciﬁ  c 
developmental disorders such as difﬁ  culties with reading, writing, 
or numeracy affect about half of the children. Visuo-spatial abnor-malities and lack of coordination have also been described. Further information: www.geneclinics.org/proﬁ  les/nf1.
Phenylketonuria
Classical phenylketonuria affects about 1 in 10 000 live born 
children in the United Kingdom. Other hyperphenylalaninaemias also occur. The disorder results from a deﬁ  ciency of the enzyme 
phenylalanine hydroxylase. The extent of the deﬁ  ciency varies, with

phenylalanine hydroxylase. The extent of the deﬁ  ciency varies, with 
a spectrum of resulting clinical conditions from classical phenylke-tonuria to benign hyperphenylalaninaemia. The gene regulating phenylalanine hydroxylase is located at 12q22-24.1. It is subject to various mutations. The classical form is inherited in an autosomal recessive manner. Prenatal diagnosis and the detection of heterozy-gotes with one defective copy of the gene are possible. About 2 per cent of cases are due to a deﬁ  ciency of tetrahydrobiopterin rather 
than phenylalanine hydroxylase.

Physical features include blond hair, blue eyes, eczema, and micro-cephaly (in half the suffers), epilepsy (in a quarter) and tremor and movement disorders or spasticity. Untreated infants have an unusu-al mouse-like body odour. In the United Kingdom all neonates are screened for the disorder. A low phenylalanine diet is usually continued through childhood. There is debate about the age at which it is appropriate to lift or relax dietary restrictions. Amino-acid supplements may be used to block phenylalanine uptake. Dietary control is essential when affected women become pregnant, because hyperphenylalaninaemia is toxic to the foetus leading to learning disability, microcephaly, and facial and heart abnormalit ies. 
Theories about the toxic effects of hyperphenylyalaninaemia include direct toxicity, competition for transport across the blood–brain barrier and dopamine depletion.
(42)

(42)
Untreated phenylketonuria is associated with a number of mala dap-
tive behaviours and behavioural syndromes including overactivity, self-injury, and autism. Autism and many of the other features do not occur in children managed with low phenylalanine diets. Those who have not been treated may have moderate to profound learning disabilities, irritability, and marked social impairments. Inadequate dietary control is associated with deﬁ  cits in mathe mat ical, visuo-spatial, and language skills. Further information: www.
nspku.org.
Prader–Willi syndrome
The prevalence is around 1 in 40 000 live born infants.(43) About

The prevalence is around 1 in 40 000 live born infants.(43) About 
70 per cent of those affected have a deletion affecting the long arm of chromosome 15 (del 15q11q13), the deleted chromosome always being of paternal origin. About 29 per cent have maternal unipa-rental disomy (MUPD) in which both chromosome 15s are inherited from mother, with no paternal chromosome 15. About 1 per cent have an imprinting error, in which the paternal chromo-some is incorrectly methylated so as to resemble a maternal one.
Infants are hypotonic or ﬂ  oppy and have feeding problems associ-

ated with a failure to suck. Many are tube fed. In early childhood there is a switch to marked overeating. Affected adults are of short stature, have small hands and feet and a characteristic pattern of facial appearance, and a lack of sexual development. Affected peo-ple were often obese, as a result of the impaired satiety leading to overeating, but modern dietary management and treatment with growth hormone in childhood may lead to near normal body size and shape. There is an increased prevalence of curvature of the spine or scoliosis and other orthopaedic abnormalities, and diabetes or heart failure may result from obesity. Life expectancy depends on severity of obesity.
(c) Behavioural, cognitive, and psychiatric aspects

Affected individuals have an almost insatiable appetite. They may steal food and consume ‘unpalatable’ food such as rotting or frozen food or pet food. A variety of sleep abnormalities and a lowering of the threshold for loss of temper may be associated. About 80 per cent pick or scratch their skin. Insistence on routines, and compul-sive behaviours are commonly reported.
(44) Severe psychiatric 
disorders including affective and psychotic states are more preva-lent, especially among people with MUPD.
(45) Anecdotal reports 
suggest the pain threshold may be raised.
About 5 per cent of those with this syndrome have overall

About 5 per cent of those with this syndrome have overall 
cognitive abilities with IQs in excess of 85, 27 per cent have border-line cognitive abilities with IQs between 70 and 85, 34 per cent have mild learning disabilities, 27 per cent moderate, 5 per cent severe, and less than 1 per cent have profound learning disability. There are deficits in auditory information processing, and relative strengths in visuo-spatial tasks. Further information: www.ipwso.org.
Rett syndrome
Rett syndrome causes severe intellectual disability in women. The prevalence in the United Kingdom is around 1 in 10 000 women.
(46)

(46)
The syndrome results from a mutation in the MeCP2 gene located at Xq28. The mutation was considered to be lethal in males but there are a small number of males with the syndrome. The severity of the syndrome in women depends on the percentage of cells with the normal MeCP2 gene active after X inactivation. If more of the X chromosomes with normal MeCP2 gene have been inactivated, the syndrome is likely to be more severe. MeCP2 acts as a mecha nistic
bridge between DNA methylation and histone methylation.
(47)

1845
The affected child appears normal at birth. For the ﬁ  rst 12 months 
no major abnormalities are apparent though the child may be placid, lack muscle tone, or be relatively immobile. She acquires skills to about 1 year with regression and loss of skills from around 18 months onwards. Speech and use of hands are particularly affected. Physical problems increase with age, and include scoliosis, 
spasticity, and leg deformities. Epilepsy is common. Pathological 
changes include a reduction in brain size with reduced cortical thickness, reduced neuronal branching, and depigmentation of the basal ganglia. Many affected girls reach adulthood, but about 1 per cent of them die each year with early death more likely with increas ing 
physical disability.

Sleep disturbance, withdrawal and episodes of crying occur during the phase of regression around 18 months of age. This is followed by a phase in which development stops. Extreme agitation and over-breathing interspersed with episodes of cessation of breathing then become apparent. The most prominent feature of the behavioural phenotype is the presence of stereotyped movements, especially midline ‘hand-wringing’ movements. Affected women and girls usually have profound learning disability. Further infor-mation: www.rettsyndrome.org.uk.
Rubinstein–Taybi syndrome

This syndrome is one of the 25 most common multiple congenital anomaly syndromes seen in genetic clinics in the United States and has an estimated incidence at 1 in 125 000 live born infants. Microdeletions at 16p13.3 have been described in some cases, and mutations in the gene coding for CREB-binding protein (CBP) found at this locus have been reported to cause the syndrome.
(48)
A few apparently familial cases have been reported, and four sets of concordant monozygotic twins have been reported.
The affected individuals are usually short, have a small head, a beaked or straight nose and downward slanting eyes. They have a stiff gait. The thumbs and ﬁ  rst toes have broad terminal phalanges,

The affected individuals are usually short, have a small head, a beaked or straight nose and downward slanting eyes. They have a stiff gait. The thumbs and ﬁ  rst toes have broad terminal phalanges, 
often with an angulation deformity. Other congenital anomalies are not uncommon. Inadequate weight gain in infancy, congenital heart defects, urinary tract abnormalities, and severe constipation contribute to morbidity reﬂ  ected in a hospitalization rate 10 times 
higher than the general population.
Findings from postal questionnaire surveys in the United States and United Kingdom indicate that people with the syndrome have a friendly disposition, a propensity to self-stimulatory activities such as rocking and an intolerance of loud noises. Reduced attention span, rocking, spinning, and hand ﬂ  apping were common in the 
UK survey.
(49) Intellectual disability is usually moderate. Further 
information: www.rubinstein-taybi.org.

UK survey.
Smith–Lemli–Opitz syndrome
This disorder is thought to occur about once in 30 000 live births. Mildly affected people may be undiagnosed. The syndrome is said to be one of the commonest autosomal recessive conditions affecting people of White European origin in North America, but 
rare among people of African or Asian origin. The male to female ratio appears to be around 3 to 1 but this may be due to the relative ease with which sexual abnormalities are detectable in men. Abnormalities in the DHCR7  gene, located at 11q12-13 results in 
deﬁ ciency of the enzyme 7-dehydrocholesterol reductase results in 
elevated levels of a cholesterol precursor. Treatment with cholesterol 
supplementation has been attempted.
(50)
During pregnancy, the foetus may show growth retardation.

(50)
During pregnancy, the foetus may show growth retardation. 
Affected individuals may have a small head, drooping eyelids, squint, forward-facing nostrils, small lower jaw, and ﬁ  nger abnor-
malities such as extra ﬁ  ngers and syndactyly. Males have abnormal-
ities of their external genitalia such as small testes or penis, hypospadias, undescended testes, and female type genitalia. Cleft palate and abnormalities of almost all major organ systems may also occur.
There is little information available about behavioural and cognitive characteristics. Intelligence varies from normal to severe learning disability. Aggressive and self-injurious behaviours and autistic spectrum disorders have been reported. Further informa-tion: www.geneclinics.org/proﬁ  les/slo.
Smith–Magenis syndrome
This syndrome, affecting around 1 in 50 000 births, is associated

This syndrome, affecting around 1 in 50 000 births, is associated 
with deletions at 17p11.2.
Affected individuals have ﬂ  attened mid-face, abnormally shaped 
upper lip, short hands and feet, single transverse palmar crease, abnormally shaped or placed ears and sometimes a high arched palate or protruding tongue. The facial features may coarsen with development. Ear and eye disorders such as otitis media and squint are relatively common.
Newborn babies with the syndrome are usually placid, ‘ﬂ  oppy’ and 
feed with difﬁ  culty. This changes to hyperactivity, self-injury (e.g. 
head banging, pulling out ﬁ  nger and toe nails and the insertion 
of objects into body oriﬁ  ces), from about 18 months onwards. Self-

hugging and mid-line hand clapping have been reported. Sleep disorders are common with some children waking repeatedly in a state of agitation. An absence of rapid eye movement (REM) sleep has been reported in some patients. Many affected children appear to be relatively insensitive to pain. Behavioural studies have been reported.
(36,51)  The severity of the cognitive impairment correlates 
with the size of the 17p11 deletion. Moderate intellectual disability is common. Speech delay is more pronounced than delay in motor achievements. Further information: www.prisms.org.

About 1 in 7000 people are affected. It is an autosomal dominant condition but up to 80 per cent of cases arise as a result of sponta-neous mutations. The disorder is genetically heterogeneous, with gene linkage to 9q34 and 16p13.10.4 syndromes causing intellectual disability

SECTION 10  intellectual disability (mental retardation) 1846
Physical features are very variable. The previously used diagnostic 
triad of epilepsy, intellectual disability and a characteristic facial skin lesion is seen in only about 30 per cent of people with the dis ease. 
The disorder is a multi-system one, with hamartomatous tumours (arising from primitive cells) affecting the brain (in about 90 per ce nt), 
skin, kidneys, heart, eyes, teeth, bones, lungs, and other organs. 
About 80 per cent of affected people have epilepsy. Brain tumours and kidney lesions are common causes of death.
Tuberous sclerosis is associated with autism and related disorders, hyperactivity and attention-deﬁ  cit disorder, obsessive and ritualis-

tic behaviour, sleep problems, and occasionally self-injurious or aggressive behaviours. Less than half of affected people have a learning disability. Attention-deﬁ  cit is common. Of those with 
learning disability, many have an IQ less than 30. Further informa-tion: www.tuberous-sclerosis.org.
Velo-cardio-facial syndrome
First described in 1978(52) this condition is relatively common, 
affecting about 1 in 2000 people. The disorder has also been called Shprintzen syndrome, Digeorge syndrome, Cayler syndrome, Takao syndrome, conotruncal anomalies face syndrome, 22q11 deletion syndrome, and CATCH22. It is associated with micro-deletions at 22q11. About 90 per cent arise de novo , with 10 per cent 
having an affected parent.

Physical features include cardiac abnormalities including ventri-culoseptal defects, pulmonary stenosis, and cardiac outlet abnor-malities; facial dysmorphology with a prominent nose with broad bridge and squared tip, small head or small lower jaw; ocular abnormalities; cleft palate; short stature and long, thin, hyperex-tensible ﬁ  ngers. The clinical features associated with the disorder 
are highly variable in both type and severity.
Many affected individuals have difﬁ  culties with reciprocal social 
interaction.(53) A high prevalence of severe psychiatric disorders is 
reported in later life, including high rates of bipolar affective disorder
(54) and schizophrenia.(55) Anxiety, social withdrawal 
and other disorders have also been described. Over 90 per cent have 
a learning disability. Speech and language problems are common. 
Further information: www.vcfsef.org.
Williams syndrome

Also known as idiopathic infantile hypercalcaemia, the syndrome affects about 1 in 15 000 infants. Most cases are sporadic though a few familial cases have been reported where the transmission seems to be autosomal dominant. The syndrome is a contiguous gene deletion disorder in which there is variable loss of genetic material involving the Elastin gene at 7q11.3 and sometimes as many as 17 nearby genes in the Williams syndrome critical region.
(56)
Infants have difﬁ  culties in feeding, are irritable, have constipation 
and fail to thrive. Over 60 per cent of children have high serum calcium concentrations. This can be treated with a low-calcium

and fail to thrive. Over 60 per cent of children have high serum calcium concentrations. This can be treated with a low-calcium 
diet and vitamin D restriction. The face is distinctive, with prominent cheeks, a wide mouth and ﬂ  at nasal bridge often described as 
‘elﬁ n-like’ . Kidney and heart lesions (especially supravalvular aortic 
stenosis and peripheral pulmonary artery stenosis) are common. Growth is usually retarded. Life expectancy is related to metabolic and heart abnormalities.
Social disinhibition with abnormal friendliness to strangers, over-activity, poor concentration, eating and sleeping abnormalities, abnormal anxiety, poor peer relationships, and abnormally sensitive hearing have been reported.
(57,58) About 95 per cent of

(57,58) About 95 per cent of 
children with the disorder have a moderate or severe learning disability. Verbal abilities are better developed than visuo-spatial and motor skills. There is an unusual command of language in which expressive language is superﬁ  cially ﬂ  uent and articulate 
but comprehension is far more limited. Further information: www.williams-syndrome.org.
Information about individual syndromes is available from the source listed 
after the relevant syndrome in the text above. O’Brien (2002)(2) gives 
information about behavioural, cognitive, linguistic and psychiatric aspects of several genetic disorders. The Contact a Family Directory of Speciﬁ  c Conditions and Rare Disorders (CaF Directory) is widely used 
for basic information about characteristics and carer organizations. 
A new paper edition is published in January each year and it is also 
available in CD-ROM format on a quarterly subscription basis: www.cafamily.org.uk.

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SECTION 10  intellectual disability (mental retardation) 1848
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10.5
Psychiatric and behaviour 
disorders among mentally retarded people
Contents
 10.5.1 Psychiatric and behaviour disorders 
among children and adolescents with intellectual disability
 10.5.2 Psychiatric and behaviour disorders among adult persons with intellectual disability
 10.5.3 Epilepsy and epilepsy-related behaviour disorders among people with intellectual disability
10.5.1 Psychiatric and 
behaviour disorders among children and adolescents with intellectual disability
Psychopathology is 2–3 times more common in intellectually 
disabled (ID) children than in the general population.(1,2)
Psychiatric disorder is the most common source of additional handicap causing loss of educational, recreational, and social 
opportunity, burden for carers and cost to the community.

opportunity, burden for carers and cost to the community. 
Numerically, the size of this problem is approximately equal to schizophrenia, but is less well-recognized due to diagnostic over shadowing in which psychiatric disorder is not differentiated from ID as a separate condition open to diagnosis and treatment.
(2)
Although there is probably a significant reduction in overall prevalence of psychiatric disorders from approximately 43 per cent 
of children to 37 per cent of young adults with ID, psychopathology 
if present in childhood is likely to persist.
(2) The proﬁ  le of disorders varies from childhood into young adult life with the prevalence of 
attention-deﬁ  cit hyperactivity symptoms decreasing, the frequency 
of symptoms of depression increasing and the prevalence of anxiety remaining stable with maturation.
(2)

(2)
There are two approaches to the description and classiﬁ  cation of 
psychopathology in young people with ID. First is the application of DSM and ICD diagnostic criteria. The reliability and validity of this approach is not well established when applied to children with ID.
(3) Y oung people with more severe ID and language impairment 
are unable to report abnormalities of their emotions, thoughts, and perceptions, which are criteria for conditions such as obsessive-compulsive disorder (OCD) and schizophrenia. Some diagnoses, for example attention-deﬁ  cit hyperactivity disorder (ADHD)
(4)
require a judgement that symptoms are inconsistent with 
developmental level, which in a child with ID is delayed relative to chronological age. The DSM-IV TR
(4) speciﬁ  es that either ADHD

(4)
(4) speciﬁ  es that either ADHD 
or separation anxiety disorder should not be made ‘exclusively during the course of a pervasive developmental disorder’ . These restrictions on comorbid diagnosis should not limit the necessity to describe the range of presenting symptoms and offer appropriate treatment, for example the use of stimulant medication in a child with autism and severe ADHD symptoms. Developmental level and degree of cognitive impairment inﬂ  uence the presentation of

symptoms. For example, children with ID are more likely than children in general, to have externalizing symptoms such as disruptive, aggressive, impulsive, or avoidant behaviours; if psychotic to experience hallucinations without delusions; or if depressed to present with irritability and stereotypies. Self-absorbed, autistic, and withdrawn behaviours are more common 
in children with severe ID whereas anxiety, disruptive, and 
aggressive behaviours are more likely in children with milder levels of ID.
(2) Some patterns of psychopathology recognized by DSM-IV 
TR(4) are specifically associated with more severe ID such as 
‘stereotypic movement disorder with or without self-injurious behaviour’ . Other emotional and behavioural disturbances seen in people with ID receive non-speciﬁ  c, atypical, or not otherwise 
speciﬁ  ed classiﬁ  cations and await better deﬁ  nition. Recent attempts

speciﬁ  ed classiﬁ  cations and await better deﬁ  nition. Recent attempts 
to produce diagnostic criteria for psychiatric disorders in people with ID (the draft ICD-10 guidelines for the psychiatric assessment

SECTION 10  intellectual disability (mental retardation) 1850
of persons with mental retardation,(5) the Royal College of 
Psychiatrists diagnostic criteria for psychiatric disorders for use 
with adults with learning disabilities(6) and the DSM-IV TR for 
intellectual disability(7) are mainly designed for use with adults and 
require clinical validation).
The second approach to the deﬁ  nition of psychopathology in 
young people with ID is the use of informant questionnaires which rate disturbed emotions and behaviour. Factor analysis produces 
subscales which have clinical utility and refer to dimensions 
of disturbance such as disruptive/antisocial behaviours, social withdrawal, self-absorbed behaviours, communication disturbance, and anxiety/depression. Two reliable questionnaires validated for use in children and adolescents with ID are the Nisonger Child Behaviour Rating form
(8) and the Developmental Behaviour 
Checklist.(9)

The multiaxial classiﬁ  cation system of DSM or ICD, revised for 
use in people with ID, should form the basis of diagnosis of psychiatric disorder in young people with ID, but are usefully supplemented with standardized information gathered from informant questionnaires.
Contributing factors and context
Assessment of the psychopathology associated with ID requires consideration of the biopsychosocial context.
(a) Cognitive proﬁ  le
A standardized cognitive assessment provides essential information

A standardized cognitive assessment provides essential information 
to inform diagnosis and guide treatment. The level of intellectual and language ability gives an indication of the child’s capacity to comprehend and communicate their perceptions, thoughts, and emotions. Subjective experiences such as grief, anxiety, hallucinations, and delusions cannot be assessed if the child is unable to communicate; therefore, psychopathology is more likely to be indirectly expressed by behaviour similar to that seen normally in younger children. For example, depression may be manifest as irritability, anxiety displayed by rocking or aggression and auditory hallucinations inferred from distressed covering of ears or self-injury.
(7) Diagnosis is more speculative when the level of ID is more

(7) Diagnosis is more speculative when the level of ID is more 
severe because the expression of emotions and behaviour is more atypical hence there is a greater use of unclassiﬁ  ed or organic brain 
syndrome diagnoses. The cognitive subtest proﬁ  le may also assist 
diagnosis. For example, children with autism usually perform better on visuo-motor tasks compared to verbal, imitation, and social comprehension tasks and therefore communicate and learn better if information is presented visually. The discovery of inattention and working memory deﬁ  cits might help to conﬁ  rm a 
diagnosis of ADHD.
As for the general population, difﬁ  cult temperamental charac-
teristics such as high levels of emotionality and activity and poor sociability, increase the risk of emotional and behavioural disorders, particularly in boys with mild ID. A difﬁ  cult temperament might

be enduring but improved parental understanding and management skills improve adaptation and reduce disturbed behaviour.
(c) Medical issues
A medical assessment is necessary, both to establish the cause of the ID, if known, and to determine if any medical conditions might be contributing to the emotional and behavioural problem. ID is associated with an increased risk of poor health in general, of brain 
disorders such as epilepsy (e.g. affecting 20 per cent of children with autism) and of medical complications associated with known causes of ID, such as cardiac and bowel abnormalities in Down syndrome, sensory impairments and deafness in Rubella embryopathy and the neuro-cutaneous brain lesions of tuberous sclerosis which are associated with tic disorder, autistic symptoms, and psychosis.
(10) Disturbed behaviour might be the only

(10) Disturbed behaviour might be the only 
manifestation of illnesses such as migraine, dental caries, and otitismedia in children with ID who are unable to talk about their pain. Psychoactive drugs are overprescribed in children with ID and their side effects are a well-recognized cause of behavioural and emotional disturbance and paradoxical effects. For example neuroleptic drugs may produce drowsiness, akathisia, and dystonic reactions. Irritability, anxiety, mood disturbance, and tics can be unacceptable side effects of stimulant medication. When prescribing drugs it is essential to systematically record behaviour and monitor side effects to conﬁ  rm that the drug has a beneﬁ  cial effect on target 
symptoms.
(9)
(d) Behavioural phenotype
Speciﬁ  c genetic causes of ID often have characteristic patterns of 
psychopathology of relevance to diagnosis, treatment, and research (see Table 10.5.1.1).
(11,12)
(e) Social and family inﬂ  uences

(11,12)
Children with ID are more likely than other children to experience 
adverse events such as poverty, socio-economic disadvantage, respite care and institutional care, rejection, social exclusion, teasing, school adjustment problems, abuse and neglect.
(13) Their 
limited cognitive ability to comprehend adverse experiences may compromise adaptation. Parental stress, grief, guilt, and mental health problems and poor socio-economic circumstances are factors which are likely to adversely affect attachment and the quality of family care and aggravate child psychopathology.
(14)
In turn, behaviour problems, communication difﬁ  culties and lack 
of social responsiveness, for example in children with autism, predict maternal stress and mental health problems and placement of the child in out of home care.
(15) Cultural responses, expectations,

(15) Cultural responses, expectations, 
and attitudes may also inﬂ  uence parenting practices and the nature 
of care provided to children with ID. Observation and assessment of the quality of care, adverse events, parental mental health, family stress, resources, and community support is necessary to understand their contribution to psychopathology and implications for management. These factors are listed in AXIS V of the draft ICD-10 guide for mental retardation.
(5)
Speciﬁ  c psychopathological disorders in 
children with ID
Behavioural disorders
(a) Attention-deﬁ  cit hyperactivity disorder
Diagnosis of ADHD in children with ID is relatively straightforward 
because the DSM-IV TR(7) and the ICD(5) criteria are based 
on observable behaviour such as distractibility and ﬁ  dgeting. This

on observable behaviour such as distractibility and ﬁ  dgeting. This 
observed behaviour must also be ‘inconsistent’ with the child’s developmental level. For example, the attention span of a 9-year-old child with a moderate ID would need to be less than that of a typical 3-year-old. Symptoms of inattention and hyperactivity

1851
must be present in at least two settings such as at home and at 
school. Symptoms of inattention and hyperactivity might also occur in reaction to stress such as bullying at school, but these adjustment disorders usually respond to psychosocial intervention and do not require medication. Anxiety and oppositional-deﬁ  ant 
disorder are common comorbid conditions which need to be considered in a management plan.
Conduct disorder and oppositional-deﬁ  ant disorder
Disruptive, aggressive, oppositional, and antisocial behaviours 
are problems in about 30 per cent of young people with mild/borderline ID, particularly males.
(2) These children usually have 
language and learning difﬁ  culties and are likely to have experienced

language and learning difﬁ  culties and are likely to have experienced 
inconsistent care and sociocultural deprivation. The diagnosis requires a consi deration of both the developmental age and the context. For example a 12-year-old young person with moderate ID might steal from a shop on the demand of a classmate without having a sufﬁ  cient understanding of social rules and the rights of 
others. These diagnoses are not applicable in non-verbal children with more severe ID where, for example, aggressive behaviour might be the only means of communicating that an experience is stressful.
(a)  Tic disorders (Tourette’s disorder) and stereotypic 
movement disorder
Tics are sudden rapid non-rhythmic recurrent motor movements 
or vocalizations in response to an irresistible urge that can be delayed.
(7) There is a comorbid association with autism or

(7) There is a comorbid association with autism or 
disruptive behaviour. Tics may emerge or deteriorate in a child with ADHD treated with stimulant medication. Relatively small 
doses of haloperidol or pimozide are often an effective treatment.(16)
Stereotypic movements are persistent, driven, non-functional, complex motor behaviours that are differentiated from tics because they appear to be intentional. They occur in 2–3 per cent of children with more severe ID. These behaviours, such as self-biting, can cause serious injury and signiﬁ  cantly interfere with daily activities, 
for example by rocking. They may be self-stimulating, occurring when the child is unoccupied, or might have communicative intent, for example to avoid an activity. The production of endogenous opioids might act to maintain the behaviours.
Emotional disorders

Clinically signiﬁ  cant symptoms of anxiety affect 10–12 per cent of 
both boys and girls with ID, compared to a prevalence in normal children of 2–5 per cent affecting twice as many females as males.
(2)
Fears are a common symptom and in children with ID are likely to be similar to the simple fears of young children in general, such as fear of the dark, loud noises, insects, and animals. Separation anxiety, typically seen in young children, can persist in older children with ID and is often complicated by fears, for example of school or other children. Children with ID are at high risk of suffering stressful experiences such as being placed in care or suffering physical and sexual maltreatment and neglect and have a limited capacity to understand stressful experiences.
(17) Therefore, 
they are vulnerable to develop post-traumatic stress disorder

they are vulnerable to develop post-traumatic stress disorder 
(PTSD). Symptoms of PTSD are usually manifest as disturbed behaviours seen typically in traumatized young children such as Table 10.5.1.1  Behaviour phenotypes
Syndrome Genetics Behavioural phenotype
Down Trisomy 21 (1 in 800 live births) Range of ID but usually moderate to severe
Relatively lower rates of psychopathology (20–30%)
Childhood: oppositional, attention-deﬁ  cit problems
Young adult: affective disorder, early-onset dementia
Fragile X Expansion of CGG trinucleotide 
sequence at Xq27.3Mild to moderate ID
Verbal IQ > Performance IQ
Shy, gaze avoidant, anxious inattentive, hyperactive, schizotypal disorder (females)
5–10% have autistic disorder but most responsive to social cues and form attachments
Behaviour may settle with age
Prader–Willi Paternal deletion long arm 
chromosome 15q 11–13 (70%)
or maternal disomy chromosome 15 (25%) 
or a mutationMild/borderline ID
Hyperphagia and food obsession

Mild obesity, serious psychopathology (50%+)
OCD (e.g. questioning, cleanliness) impulsivity, aggression, deﬁ  ance, skin picking
In adolescents anxiety, depression, psychosis (with maternal disomy)
Smith Magenis Chromosome deletion at 17p 11.2 Moderate ID
Severe psychopathology: hyperactive, impulsive, aggressive, insomnia, stereotypic movements 
(e.g. self-hugging) self-injury (e.g. nail pulling, head banging)
Williams Micro-deletion on chromosome 7q 11.23 
(elastin gene)Moderate ID
Visuo-spatial/motor deﬁ  cits but recognize facial features, loquacious with stereotypic phrasesChildren: endearing, ‘elﬁ  n-face’, irrepressible, and affectionate, hyperacusis, phobias, anxiety, 
inattention, insomnia10.5.1  psychiatric and behaviour disorders among mentally retarded people

SECTION 10  intellectual disability (mental retardation) 1852
repetitive play, behaviours which re-enact the trauma, nightmares, 
withdrawal, increased startle response, and hyper-vigilance.(7)
PTSD in children with ID is underdiagnosed and research on its phenomenology is required. The diagnosis of obsessive-compulsive disorder in young people with ID is problematic because they may not have sufﬁ  cient language to describe persistent thoughts 
and their attempts to suppress these thoughts. They also do not recognize that their compulsive behaviour is unreasonable. Stereotypic self-injurious behaviours might be regarded as evidence for an OCD, but these behaviours do not usually respond to treatments for anxiety. Some drugs that are an effective treatment of OCD in young people in the general community, such as sertraline and clomipramine, are used for the treatment of anxious compulsive behaviours in young people with ID but their efﬁ  cacy 
has not been investigated.

(b) Mood disorder
Depression in young people with ID is more prevalent than in other children.
(2) Adolescents with moderate to severe levels of ID, 
provided they have some language, are able to reliably report sad feelings, but the diagnosis is confirmed by the presence of behavioural symptoms such as irritability, loss of interest in usual activities, loss of appetite and weight loss, sleep disturbance, crying, and withdrawn and regressed behaviours (e.g. rocking).
(7) A daily 
carer completed record of mood and activity may reveal a pattern of cycling bipolar or unipolar mood disorder and is a useful record to document response to treatment.
(9)
Pervasive developmental disorders

(9)
About 75 per cent of children with autism have ID. There is also an increased association with epilepsy, tuberous sclerosis, congenital rubella syndrome, and phenylketonuria and comorbidity with ADHD, OCD, anxiety, depression, and tic disorder. These comorbid symptoms might be epiphenomena of autism related to fronto-striatal dysfunction, but it is helpful to the child and family to identify any comorbid symptoms and to treat them appropriately.
(18)
Children with ID also have delayed language and may have stereotypic behaviours and a limited range of interests, but they can be differentiated from those who also have autism because they try to communicate, use gesture and imitation, have reciprocal play and respond with emotion in a manner appropriate to their developmental level.
Principles of management

Effective management begins with a multiaxial diagnostic formulation based on the DSM or ICD which describes the child’s psychopathological disorder, cognitive profile, temperamental characteristics, genetic and associated medical conditions, level of adaptive functioning, and the family and sociocultural context. The delivery of effective management usually requires the involvement of a multidisciplinary team with a clear deﬁ  nition of 
roles and regular communication between professionals, parents, and teachers, for example at a case conference. The involvement of parents as partners in speech, physio, and behaviour therapy improves outcome and facilitates treatment compliance. Parent education and skills training reduces parental stress and improves parental mental health and child behaviour.
(19) Family therapy may 
help reduce family conﬂ  ict and improve communication and child 
management, but outcome research is required.Psychological treatment

Effective behaviour modiﬁ  cation techniques based on operant 
conditioning principles teach positive socially adaptive behaviours and reduce difﬁ  cult behaviours.
(20,21) Antecedent triggers, the 
functions of the behaviour and any rewarding consequences which reinforce the behaviour are identiﬁ  ed. Intervention might focus 
on changing the antecedent events, for example by removal of an upsetting sound. Replacement of the disruptive behaviour might be achieved by rewarding alternative appropriate behaviour or by teaching a new behaviour which improves communication such as the use of pictures to communicate a need. A further approach which may help extinguish difﬁ  cult behaviour is a non-aversive 
modiﬁ  cation of the usual response to the behaviour such as

modiﬁ  cation of the usual response to the behaviour such as 
moving away from a screaming child instead of paying them attention. Counselling and cognitive behavioural therapy including relaxation exercises, which is modiﬁ  ed to take into account the 
developmental level and language ability of the child with ID 
might reduce anxiety and depression, but its effectiveness requires further research.
Drugs, if used to treat specific symptoms, should be part of a psychosocial and educational management plan, which includes informed parent/carer consent and participation. Evidence for the efﬁ  cacy of psychotropic drugs in children with ID is limited,
(16)
but children with ID are prescribed or even overprescribed 
drugs on the basis of evidence for their use in either adults with ID

(16)
drugs on the basis of evidence for their use in either adults with ID 
or in normally developing children. These drugs include stimulant medication, atomoxetine, clonidine, neuroleptic drugs, and imipramine for ADHD; clomipramine and selective serotonin reuptake inhibitors (SSRIs) for OCD and stereotypic self-injurious behaviour; SSRIs for depression; neuroleptic drugs for tic disorders. Rigorous empirical studies have failed to demonstrate clear beneﬁ  t 
for the use of ‘typical’ neuroleptic medication such as chlor-promazine in the treatment of disruptive behaviour. There is empirical evidence that low doses of haloperidol or risperidone (0.02–0.06 mg/kg/day) are an effective treatment for disruptive stereotypic behaviour.
(22) Problematic side effects, particularly

(22) Problematic side effects, particularly 
for haloperidol, are drowsiness, akathisia, dystonia, and tardive dyskinesia. Weight gain, prolactinemia, and metabolic disturbances such as diabetes are serious side effects of risperidone. Anticonvulsants used as mood stabilizers (sodium valproate, carbamazapine, and lamotrigine), lithium, β-blockers, and 
buspirone have been shown, mostly in open trials, to reduce self-injurious and episodic aggressive behaviours. Opiate antagonists (naloxone and naltrexone) may reduce self-injurious behaviour. Difﬁ cult sexual behaviour in adolescent males with ID can be 
treated with testosterone antagonists to reduce libido. In many countries this treatment requires approval and monitoring by an independent committee. The prescription of psychotropic drugs requires regular follow-up to monitor compliance, side 
effects, and response to treatment using behaviour observations 
and carer completed symptom checklist such as the DBC
(9) or 
NCBRF.(8)

(9) or 
NCBRF.(8)
Early intervention
There is growing evidence that broad-based early intervention for young children with developmental delay, such as those with

1853
autism, promotes adaptive behaviour and skill development. The 
components of effective early intervention include:
1 Parent education and skills training and the management of 
parent mental health problems such as depression.(19)
2 Regular medical review and treatment of associated conditions 
such as epilepsy and any inter-current illness or psychopatho-logical disorder, which might compromise behaviour.
(10)
3 A structured behaviour management and social and 
communication skills programme.(21)
4 Family support, respite care, home help, and holiday programmes.
5 Speech, occupational, and physiotherapy to develop communi-
cation, sensory, motor, and play skills.
6 Assisted education and socialization at preschool and school.
Children with ID often suffer the added handicap of emotional and 
behavioural disorder which seriously compromises their adjustment and causes signiﬁ  cant extra burden and cost for their parents and

behavioural disorder which seriously compromises their adjustment and causes signiﬁ  cant extra burden and cost for their parents and 
the community. A comprehensive biopsychosocial assessment of the child and family provides the context for understanding psychopathological symptoms and the basis for a best practice management plan incorporating psychological, educational, family, and perhaps pharmacological interventions.
Bouras, N. and Holt, G. (eds.) (2007). Psychiatric and behavioural disorders 
in intellectual and developmental disabilities  (2nd edn). Cambridge 
University Press, London.
Reiss, S. and Aman, M.G. (1998). Psychotropic medication and developmental 
disabilities: the international consensus handbook . Ohio State University, 
Columbus.
Therapeutic Guidelines. (2005). Management guidelines: developmental 
disability  (Version 2). Therapeutic Guidelines Ltd., North Melbourne.
www.cddh.monash.org (provides an educational programme in the

www.cddh.monash.org (provides an educational programme in the 
psychiatry of ID).
www.iassid.org (review of current research and information exchange on 
the psychiatry of ID).
1. Emerson, E. (2003). Prevalence of psychiatric disorders in children 
and adolescents with and without intellectual disability. Journal of 
Intellectual Disability Research ,47, 51–8.
2. T onge, B.J. and Einfeld, S.L. (2003). Psychopathology and intellectual 
disability: the Australian child to adult longitudinal study. International 
Review of Research in Mental Retardation ,26, 61–91.
3. Einfeld, S.L. and T onge, B.J. (1999). Observations on the use of the 
ICD-10 guide for mental retardation. Journal of Intellectual Disability 
Research ,43, 408–12.
4. American Psychiatric Association. (2002). Diagnostic and statistical 
manual of mental disorders  (4th edn, text revision). American Psychiatric

manual of mental disorders  (4th edn, text revision). American Psychiatric 
Association, Washington, DC. 5. World Health Organization. (1996). The ICD-10 guide for mental 
retardation . World Health Organization, Geneva.
 6. Royal College of Psychiatrists. (2001). DC-LD (Diagnostic criteria for 
psychiatric disorders for use with adults with learning disorders/mental retardation) . Gaskell, London.
 7. Fletcher, R., Loschen, E., Stavrakaki, C., et al.  (2007). Diagnostic Manual 
– Intellectual Disability (DM-ID): a textbook of diagnosis of mental 
disorders in persons with intellectual disability . NADD Press, Kingston, 
New Y ork.
 8. Aman, M.G., Tasse, M.J., Rojahn, J., et al.  (1996). The Nisonger 
CBRF: a child behaviour rating form for children with developmental disabilities. Research in Developmental Disabilities ,17, 41–57.

 9. Einfeld, S.L. and T onge, B.J. (2002). Manual for the developmental 
behaviour checklist  (2nd edn). Centre for Developmental Psychiatry & 
Psychology, Monash University, Melbourne.
10. Therapeutic Guidelines. (2005). Management guidelines: developmental 
disability  (Version 2). Therapeutic Guidelines Ltd., North 
Melbourne.
11. Dykens, E.M. (1999). Direct effects of genetic mental retardation 
syndromes: maladaptive behaviour and psychopathology. International 
Review of Research on Mental Retardation ,22, 1–26.
12. Einfeld, S.L., T onge, B.J., and Rees, V .W. (2001). Longitudinal course of 
behavioural and emotional problems in Williams syndrome. American 
Journal of Mental Retardation ,106, 73–81.
13. Emerson, E., Graham, H., and Hatton, C. (2006). The measurement

13. Emerson, E., Graham, H., and Hatton, C. (2006). The measurement 
of poverty and socioeconomic position in research involving people with intellectual disability. International Review of Research in Mental 
Retardation ,32, 77–108.
14. Baker, B.L., Blacker, J., Crnic, K.A., et al.  (2002). Behaviour problems 
and parenting stress in families of three-year-old children with and without developmental delay. American Journal of Mental Retardation ,
107, 433–44.
15. Llewellyn, D., McConnell, D., Thompson, K., et al.  (2005). Out-of-
home placement of school age children with disabilities. Journal of 
Applied Research in Intellectual Disability ,18, 1–16.
16. Reiss, S. and Aman, M.G. (1998). Psychotropic medication and 
developmental disabilities: the international consensus handbook
.
Ohio State University, Columbus, OH.

.
17. Hatton, C. and Emmerson, E. (2004). The relationship between 
life events and psychopathology amongst children with intellectual disabilities. Journal of Applied Research in Intellectual Disability ,
17, 109–17.
18. T onge, B.J. and Rinehart, N.J. (2007). Autism and attention deﬁ  cit/
hyperactivity disorder. In Neurology and clinical neuroscience
(ed. A.H.V . Shapira), pp. 129–30. Mosby, Elsevier, Philadelphia.
19. T onge, B.J., Brereton, A.V ., Kiomall, et al.  (2006). Effects on parental 
mental health of an education and skills training program for parents with young children with autism: a randomized controlled trial. Journal of the American Academy of Child and Adolescent Psychiatry ,
45, 561–69.
20. Lucyshyn, J.M., Dunlap, G., and Albin, R.W. (eds.) (2002). Families and

20. Lucyshyn, J.M., Dunlap, G., and Albin, R.W. (eds.) (2002). Families and 
positive behaviour support . Brookes, Baltimore.
21. Emerson, E. (2001). Challenging behaviour .Analysis and intervention 
in people with severe intellectual disabilities  (2nd edn). Cambridge 
22. Aman, M.G., DeSmedt, G., Derivan, A., et al.  and the Risperidone 
Disruptive Behaviour Study Group. (2002). Risperidone treatment of children with disruptive behaviour symptoms and sub-average IQ: 
a double blind, placebo-controlled study. The American Journal of 
Psychiatry ,159, 1337–46.10.5.1  psychiatric and behaviour disorders among mentally retarded people

SECTION 10  intellectual disability (mental retardation) 1854
10.5.2 Psychiatric and behaviour 
disorders among adult persons with intellectual disability
The behavioural and emotional difﬁ  culties that are experienced by 
adults with intellectual disability (ID) have been regarded for many years as manifestations of their intellectual deﬁ  cits and maladap-
tive learning. The awareness that these persons may also suffer from mental illness was a notion that came into being in the mid-nineteenth century.
Nevertheless, the psychiatric problems of individuals with ID 
were continually ignored in the ﬁ  rst half of the twentieth century. In 
the past three decades, the ﬂ  ourishing normalization philosophy

the past three decades, the ﬂ  ourishing normalization philosophy 
has highlighted the psychiatric problems of this population once again and rekindled the interest of practitioners, scientists, and ser-vice providers. Systematic studies have been performed which indi-cate that the full spectrum of psychiatric disorders as we know them today can be identiﬁ  ed among the persons with ID. Moreover, it is 
probable that they may be prone to a psychopathology that is deter-
mined by the speciﬁ  cs of their biological and psychosocial being.
Features affecting presentation
Studies indicate that the types of psychiatric symptoms and

Studies indicate that the types of psychiatric symptoms and 
syndromes that are observed among persons with borderline and mild ID are similar to those encountered among the population in general. Amongst individuals with moderate and severe ID, how-ever, the presentation of mental illness may be less typical, and the diagnosis more difﬁ  cult to establish.
Sovner and Hurley
(1) have categorized four factors which may 
inﬂ uence the presentation of mental illness among the persons 
with ID: intellectual distortion (impaired ability to conceptualize feelings and to communicate them to others), psychological masking (lack of usual richness of the symptomatology found in general population), cognitive disintegration (inclination to become disorganized and to exhibit regressive behaviour), and baseline exaggeration (increase of pre-existing maladaptive behaviour by

emotional stress or mental illness).
Hucker et al .
(2) pointed to a generally banal symptomatology 
encountered among these individuals, often accompanied by regression to a child-like state of dependency and hysterical features. Behavioural disturbances were often more important than symptomatic complaints as indicators of psychiatric disorders.
Apparently, the lower the IQ, the more the symptoms of mental 
illness tend to lose their speciﬁ  city, or take on a different meaning 
than is the case with the intellectually normal population. This, undoubtedly, makes it difﬁ  cult to establish a conﬁ  dent diagnosis of 
mental illness in people with severe ID.
(3)
The following is a concise survey of the striking clinical features 
of mental illness and behaviour problems as they occur among adult persons with ID.Mental illness
(a) Psychosis
Among persons with mild ID, classical clinical features are present in psychotic states. The symptoms tend to be ﬂ  orid but banal. In

Among persons with mild ID, classical clinical features are present in psychotic states. The symptoms tend to be ﬂ  orid but banal. In 
schizophrenia, for example, there is a high incidence of delusions and hallucinations, which reﬂ  ect the limited experiences, naive and 
wishful thinking, interests, and social horizon of the patient. Ideas, 
that have been inﬂ  uenced by radio, television, etc., are found fre-
quently. Catatonic features with odd postures and slowness are common. Impulsive, aggressive, auto-aggressive, and bizarre behav-iours may dominate the clinical pictur e. In the ch ronic-phase apathy, 
lack of motivation and social withdrawal are common.
(4,5) Increase 
of ‘negative’ schizophrenic symptoms and decrease of functional abilities were observed in the group with ID when compared with the group from general population with schizophrenia.
(6)
Establishing the diagnosis of schizophrenia in persons with more

(6)
Establishing the diagnosis of schizophrenia in persons with more 
severe ID can be a difﬁ  cult task because of verbal communicative 
difﬁ culties. Reid(7) considers it to be impossible to establish such a 
diagnosis among persons who only communicate non-verbally. However, the problem of establishing the diagnosis does not mean that psychotic conditions do not occur in these individuals. T o the 
contrary, it is likely that different sorts of psychosis occur in this population more frequently than in general population (see Chapter 4.5.2).
Short-term psychotic states (lasting several days or weeks), usu-

ally beginning rather suddenly after a stressful event, are found relatively often among adolescents and young adults with ID. Early Dutch psychiatric literature refers to these states as ‘debility psychosis’ . The symptoms may be heterogeneous, and remission is usually complete. These persons usually revert fully to the premor-bid level of functioning. However, recurrence is frequent.
Establishing the diagnosis of atypical psychosis (contrary to 
diagnosing schizophrenia) is, for an experienced practitioner, possible even with patients who have no language development and are at a severe level of ID. The primary symptoms are changes in interactional patterns, changes of posture and movement, odd and bizarre behaviour, disturbances of the physiological functions, expression of emotional tension (e.g. anxiety, irritability), aggression, and self-injuring behaviour.
(b) Major depression and bipolar disorders

Depressed mood and vegetative symptoms are the most striking symptoms, even though complaints of depression are not always expressed. A depressive mood often is not verbalized, particularly among individuals at a lower intelligence level, but may well be observable. Similarly, the elevation of mood in mania is usually not expressed verbally either. Atypical features such as regression to child-like dependency, incontinence, loss of social skills, and hysterical symptoms such as pseudo-ﬁ  ts and paralysis may mask 
classical symptomatology. In persons with a more severe disability, depression should be suspected where there is a change or onset of behaviour problems like stereotypic behaviour, tantrums, aggres-sion, and self-injuring behaviour.
(4,8) Catatonic features and visual 
hallucinations, particularly among persons at lower intelligence levels, have also been reported.
(2,9,10)  The atypical symptomatology

(2,9,10)  The atypical symptomatology 
among persons on lower developmental levels may require modiﬁ  -
cation of standard diagnostic criteria.
Aggressive behaviour was observed in 40 per cent of the depressed 
subjects.(11) Self-injuring behaviour has often been reported as well.

1855
Suicidal behaviour has hardly ever been studied in this population, 
and suicidality is very rare among the more severely handicapped. This symptom is, however, not rare among depressive patients at a mild level of ID.
Some investigators report the relatively frequent occurrence 
of rapid-cycling affective disorder,
(12) particularly in persons 
with more severe disability. Episodes of particular mood or of an undifferentiated mood-like dysphoria or irritability have a short duration, and may be expressed in terms of days or weeks.
(9)
Researchers assume that these disorders, in persons with ID are often related to organic brain disorders, that is, metabolic, neuro-endocrine, and other neurological disorders.
In mixed bipolar disorder, there is either the simultaneous 
presence of manic and depressive features, or these features follow each other rapidly. Schizoaffective psychoses are also described among these individuals.
(c) Dysthymic disorder

Dysthymia is a relatively common disorder among persons with mild and moderate ID.
(9,13)  Nevertheless, publications on this 
disorder are rare. The symptomatology includes loss of energy and interest, negative self-image, feelings of helplessness, anxiety, and signiﬁ  cant behavioural problems such as irritability, anger, destruc-
tibility, and aggression. The disorder is often related to a speciﬁ  c

tibility, and aggression. The disorder is often related to a speciﬁ  c 
stress, for example, termination of an affective relationship, change in the surroundings, hospitalization, etc. Chronic states, dating back to the childhood or the teens, possibly caused by chronic overdemanding, social deprivation, or repeated abuse, may be interrupted by episodes of major depression, usually elicited by acute stress (so-called ‘double depression’ , see Chapter 4.5.3). Došen and co-workers found this disorder relatively frequent in adoles-cents and young adults with ID and called it ‘developmental depression’ .
(10, 14)  Social interactional problems, poor social skills, 
and difﬁ  culties related to emotional development are considered to 
be predisposing factors for this disorder.(14)
(d) Anxiety disorders
The most commonly reported anxiety disorders are simple phobia, social phobia, and generalized anxiety disorder.
(4) It seems that adults

(4) It seems that adults 
with ID have fears similar to those of children who are at the same mental age: fear of separation, fear of natural events, fear of injury, and fear of animals. The anxieties and fears are probably related to the traumatic events and cumulative failure experiences that these persons have. The presentation may be through behaviour problems, irritability, problems with sleeping, or somatic complaints.
(5) In a 
panic disorder, a sudden onset, blacko uts, aggression, sweating, and 
shaking may be observable. The obsessive–co mpulsive disorder may 
be difﬁ  cult to diagnose in persons with ID because they do not resist 
against such feelings and the anxiety is often absent. According to some authors,
(4) the diagnosis can be established with the emphasis

(4) the diagnosis can be established with the emphasis 
being on the externally observable behavioural components, despite of absence of some internal states like anxiety and resistance. Post-traumatic stress disorder is likely to occur in this population, follow-ing relatively less severe stress than among general population. The diagnosis in those who are unable to communicate their experiences should be based on changes in a person’s behaviour, mood, and level of functioning following a traumatic event.
(4)
(e) Autism spectrum disorder
Autism spectrum disorders have been estimated to be present in 10 per cent of persons with mild ID and 40 per cent of those with severe ID, and account for a large proportion of behaviour 
disorders. It also appears that mental illness occurs frequently as a secondary disorder among these individuals.
A possible relationship between affective illness and pervasive

A possible relationship between affective illness and pervasive 
developmental disorder has been suggested by various investiga-tors
(12); however, this phenomenon has been examined insufﬁ  -
ciently and is clearly an area that future research can be directed to. In clinical practice, we have encountered a number of cases of pervasive developmental disorder together with secondary atypical psychosis. Inexperienced practitioners are inclined to diagnose schizophrenia in such cases. However, thorough developmental history will reveal sufficient information to make diagnostic differentiation possible. Other problematic behaviours such as anxious, aggressive, auto-aggressive, or disruptive behaviour are frequently found among persons who have an autism spectrum disorder and ID.
(15) In our opinion, these behaviours should be

(15) In our opinion, these behaviours should be 
seen as being secondary disorders instead of as part of the autistic disorder.
(f) Dementia
In individuals with dementia, the typical features such as memory impairment, personality change, loss of social skills, and deteriora-tion in habits are always present. Behavioural problems may be the most obvious manifestation. Nocturnal confusion, transient psy-chotic episodes, and late-onset epilepsy should always alert one to the possibility of a dementing illness in the ageing person with ID. Memory loss is generally difﬁ  cult to identify in the early stages, but 
becomes more obvious as the illness progresses. Medical risk fac-tors include a history of hypertension, ischaemic episodes, neuro-logical symptoms, organic brain damage, and a family history of dementia. Dementia Alzheimer type in persons with Down syn-drome presents a similar picture and is usually associated with gen-eralized premature ageing.

Behaviour disorders—challenging behaviour
Behaviour disorders including aggression, self-injury, destructive-ness, and disruptive, maladaptive, and antisocial behaviour occur commonly among persons with ID. Such behaviour has recently been called challenging behaviour, which emphasizes the need for appropriate care and supervision. These disorders are usually asso-ciated with severe ID, but can also occur in individuals who are at a moderate and mild level of ID.
Various attempts have been made to distinguish between behav-
iour disorders and psychiatric illness in these individuals. Gardner and co-workers
(16) have proposed a bio-psycho-social diagnostic

(16) have proposed a bio-psycho-social diagnostic 
approach, which takes account of the multiple factors underlying and maintaining the behaviour disturbances of a particular individual. They point out that behaviour disorders with a neuropsychiatric and organic basis can still acquire a functional component if they are being reinforced by the environment or are of value to the individual. Another approach is from the develop-mental perspective,
(3,17) viewing behaviour disorders as the result 
of a lack of real understanding of the person’s developmental aspects and interactional problems.
(a) Aggressive behaviour

Aggressive behaviour is a common problem among persons with ID. The symptom of aggression is often a feature of the psychosis, depression, or antisocial personality disorder, and is often described in genetic disorders such as the fragile X, Prader–Willi, and 10.5.2  psychiatric and behaviour disorders among adult persons with intellectual disability

SECTION 10  intellectual disability (mental retardation) 1856
Klinefelter syndromes. Learned aggression through the imitation 
of aggressive models or as a function of communication is also found relatively frequently among people with ID.
(b) Self-injurious behaviour
Self-injurious behaviour occurs more often among persons with moderate and severe ID (IQ < 50), beginning sometimes in toddler age and most frequently between the ages of 10 and 20. The occurrence of self-injurious behaviour is related to genetic and organic disturbances and adverse environmental and development conditions. Certain psychiatric disorders such as depression and psychosis may also elicit self-injurious behaviour.
(c) Offending behaviour
Owing to their behaviour problems, these individuals may become 
involved in activities, that bring them into conﬂ  ict with the law. 
Insufﬁ  cient understanding of their problems and needs may result

Insufﬁ  cient understanding of their problems and needs may result 
in their not receiving the appropriate support from the social services. The typical offender with ID is, according to Day,
(18) a 
young male functioning in the mild to borderline intellectual range, from a poor urban environment, with a history of psychosocial deprivation, behaviour problems, and personality disorder. The most common offences are acquisitive and technical, but sex offences and arson are considerably overrepresented.
Various investigators have reported personality disorders among persons with ID.
(19,20) The relevance of the concept of personality 
disorder, in particular with regard to the persons with more severe ID, has been questioned by a number of investigators. Apparently, in these persons, besides the problem of personality disorders, there is a problem of personality development. Zigler and colleagues

(21)
have explored personality traits thought to be particularly salient in determining the behaviour of individuals with ID. Levitas and Gilson
(22) have stressed the importance of a crisis period during 
the process of personality development and the related psychoso-cial aspects. Other developmentally oriented authors
(14,23)  make a 
link between, on the one hand, the problematic processing of particular phase–speciﬁ  c aspects of emotional development and 
ego structuring, such as the achievement of secure attachment, an intercompetitive separation-individuation process, and the estab-lishing of ego functions, and, on the other hand, the increased vulnerability of these individuals to particular psychiatric disorders such as depression, social withdrawal, disruptive behaviours, etc. Classiﬁ  cation of personality problems within the existing diagnos-
tic categories for personality disorders in general population is questionable and requires modiﬁ  cation of particular diagnostic

tic categories for personality disorders in general population is questionable and requires modiﬁ  cation of particular diagnostic 
criteria.
(4, 5) It is unlikely that personality disorders could be diag-
nosed in persons with severe/profound ID.
It appears that the main problem at the root of the personality 
disorders of individuals with ID pertains to an underdeveloped personality structure in relation to a delay in psychosocial develop-ment. One is then inclined to speak of an immature rather than a disturbed personality.
Diagnosis calls for a full and detailed history, careful observation 
of the patient, knowledge of the natural history of the illness, and the elimination of irrelevant factors (for further information about assessment, see Chapter 10.1).Assessment

In complex cases, a period of inpatient observation or explorative treatment may be necessary. As full a history as possible of the current illness should be obtained from the patient, together with corroborative histories from the relatives and carers. The standard-ized format of psychiatric history should be supplemented by a detailed developmental history, a description of current social functioning, environmental circumstances, associated somatic disorders and physical disabilities, and the aetiology of the ID. Enquiries should be focused on behavioural changes such as sleep disturbance, loss of appetite, weight loss, lack of interest, bizarre behaviour, restlessness, anxiety, withdrawal, and any other devia-tions from customary behaviour. Precipitating factors such as

stressful events and possible predispositions to reacting in a particu-lar way in a particular situation should be explored. Full details of

previous psychiatric illnesses suffered by the patient and the family history of mental illness should be obtained. Because of the general paucity of subjective complaints by persons with ID, the examiner must rely more on objective data regarding the patient’s appear-ance, manner of communication, facial expression, evidence of hallucinations, posture, etc. If called for, direct observations should be made in as wide a range of settings as is necessary. T o these ends, a video recording of the patient in his or her natural surroundings may provide important information about the interactional pattern of the patient and his or her surroundings. The psychiatric exami-nation is usually supplemented by somatic, neurological, neuro-physiological, biochemical, and psychological examinations. Assessment of the level of ID is crucial for diagnostic consideration. Currently, in psychological assessment, besides examination of cognitive functioning, the emphasis is on determination of

Assessment of the level of ID is crucial for diagnostic consideration. Currently, in psychological assessment, besides examination of cognitive functioning, the emphasis is on determination of person-ality development and the level of emotional development.

(3)
Diagnosis
IQ assessment, personality development, emotional level, and measuring adaptive behaviour can provide extra background information that may be useful to the diagnosis. Speciﬁ  c tests, for 
example, of thought disorder in schizophrenia, may be helpful in establishing the diagnosis, but are not yet standardized for this population. Non-invasive neuroimaging techniques promise to be potentionally valuable diagnostic tools, particularly for non-verbal persons with severe ID in the future. Structured interview schedules and rating scales are being used increasingly in an attempt to improve diagnostic accuracy. Instruments developed for use with persons without ID rely heavily on the ability of the patient to 
describe subjective feelings and are thus of limited value. Diagnostic 
rating scales that are to be used with the persons with ID should, as far as possible, reﬂ  ect behavioural rather than subjective com-
ponents. An early attempt was made by Huck er and colleagues,

(2)
who published diagnostic criteria for mania, depression, and 
schizophrenia for use with persons with ID; these have been fur-ther reﬁ  ned by Sovner and Hurley
(1) and by Menolascino and 
Weiler.(24) Recently, a number of scales have been developed 
speciﬁ  cally for use with this population, and different other instru-
ments are in development. These scales were primarily developed for use as research instruments, and whilst they play an invaluable role in epidemiological studies and population screening as well as being useful for monitoring the response to treatment, they are of limited value in clinical practice and rarely, if ever, solve a diagnostic problem.

1857
(a) Integrative psychiatric diagnosis
For clinical purposes, it has been proposed that more elaborate and 
expanded diagnostic formulations be made.(25) Such diagnosis 
should incorporate diagnostic categories as well as the onset mech-anisms of the psychopathology, biological aspects, psychological functioning, milieu characteristics, life problems, psychosocial needs, and individual strengths. Diagnostics of this sort have been called integrative diagnosis and are an attempt to adapt conven-tional diagnostic criteria to the complex problems of individuals with ID.
(3,14) During the diagnostic process, particular attention is 
paid to describing the onset mechanism of the psychopathological phenomenon by which the dynamics of different nosological factors come into scope and become more understandable to the direct carers and professional helpers. A better understanding of the processes involved in the mental illness is important to the treatment approach.

Numerous attempts have been made to apply the traditional 
psychiatric diagnostic categories of ICD-10 and DSM-IV to the psychopathology of persons with ID. Their applicability to these individuals has, however, been questioned.
(1,2,25) Whilst the ICD 
and DSM criteria may be applied to people functioning in the mild to borderline ID ranges without alteration or with little modiﬁ  ca-
tion, they become increasingly unreliable as the severity of intel-lectual disability increases. The limited communication skills of these persons make it very difﬁ  cult to ascertain the presence of cer-
tain symptoms such as delusions and hallucinations. As the role of underlying organic brain damage expands, the phenomenology becomes increasingly more characterized by a range of atypical symptoms. The non-speciﬁ  c nature of behavioural disturbances 
further confounds diagnostic endeavours. Szymanski,
(25) among

(25) among 
others, has pointed out that behaviour disturbance is not a psychi-atric condition but a symptom, and Reid
(26) has drawn attention to 
the fact that behaviours, that would be deemed abnormal in people functioning in the average intellectual range may be developmen-tally appropriate to the mental age of a person with severe ID.
Other authors
(3,17,27) suggest using the developmental perspec-
tive when attempting to understand and diagnose the psychiatric and behavioural disorders of the persons with ID. They point out that there are ﬁ  ndings which suggest that there may be a relation-
ship between certain developmental levels and syndromes and spe-ciﬁ c neuropsychiatric disorders (see below). Some investigators 
argue that syndromes should be empirically derived, and a ‘dimen-sional’ approach would be a more effective way to classify psycho-pathology than the categorical system.
(28,29)  Van Praag(30) proposes

(28,29)  Van Praag(30) proposes 
a ‘functional psychopathology model’ emphasizing functional problems of the CNS on the background of psychiatric disorders.
Not surprisingly, there have been calls for some modiﬁ  cations 
of existing DSM and ICD diagnostic criteria with the introduction of behavioural equivalents for some symptom criteria as well as for development of a broader taxonomy, which takes account of the atypical presentation of mental illness in this population.
(31)
Overall prevalence
Psychiatric disorder appears to be more common among the persons with ID than in the general population. Overall prevalence rates range from 20 per cent to 74 per cent,
(19,25,32)  depending on

(19,25,32)  depending on 
the diagnostic criteria employed, the type of disorder screened (whether or not behaviour disorders are included, for example), the nature of the sample (community or institution), the type of data collected (case note studies or new data), and the level of ID, ages, and gender of the populations studied. Higher rates of psychiatric disorder have been reported in some studies among the individuals with severe ID in comparison with the person on mild ID level. For further information concerning epidemiology, see Chapter 10.2.
Aetiology

Aetiology
Investigators of aetiology agree that the high prevalence of psychi-atric disorders among persons with ID is related to a wide range of neurological, psychological, social, and personality risk factors including impaired genetic factors, delayed cognitive, emotional and social development, organic brain damage, communication problems, environmental problems, and family psychopathology. Alone or in combination, these factors increase the vulnerability of the person with ID to psychiatric and behavioural problems.
Theories
Achenbach and Zigler(33) have pointed out the importance of social 
incompetence as a factor playing a role in interactional and intra-psychic problems. This theoretical perspective has received support from studies in which discrepancies between self-image and the 
expectations of others have been shown to be a fertile breeding 
ground for the onset of psychopathology. Menolascino
(34) empha-

sized the importance of neurophysiological and sociological devel-opmental processes which may have a different timing and take a different course in these individuals, causing deviations from nor-mal development; this is known as the biodevelopmental theory. Matson
(35) proposed the biosocial theory, which hypothesizes that 
due to speciﬁ  c biological factors (neurological, biochemical, genet-
ic, etc.) together with speciﬁ  c social factors (family interactions, 
culture, and other environmental variables), and speciﬁ  c psycho-
logical processes (cognitive development, personality variables), the psychopathology of persons with ID differs in a number of ways from that of persons without ID.
Tanguay,
(36) Došen,(3,14,17)  and Gaedt and Gärtner(37) have

Tanguay,
(36) Došen,(3,14,17)  and Gaedt and Gärtner(37) have 
applied the developmental approach to the understanding of the symptoms of psychopathology and to the psychiatric diagnostics in these individuals. These authors based their approach on Piaget’s stages of cognitive development as well as on Mahler’s and Bowlby’s models of psychosocial development. Parallels could be drawn between the symptoms of psychopathology of children without ID at a particular chronological age and individuals with ID at the same developmental age, which indicates that the developmental level may speciﬁ  cally affect the exterior features of mental illness. 
According to these authors, although developmentally disabled adults who suffer from mental illness resemble other adults in many ways, it is the developmental level and consequent differen-tiation of psychosocial life (e.g. affect differentiation, personality 
structuring, moral development), that may be decisive for the

structuring, moral development), that may be decisive for the 
symptoms linked to the disorder. For example, because of their underdeveloped psychosocial life, adults with severe ID display little differentiation in their symptomatology. They exhibit agitation, aggression, self-injurious behaviour, or other disruptive 
behaviours, which in other people may be indicative of various 10.5.2  psychiatric and behaviour disorders among adult persons with intellectual disability

SECTION 10  intellectual disability (mental retardation) 1858
underlying mental illnesses such as anxiety disorder, depression, or 
psychosis. Similarly, a toddler may have ‘tantrums’ when frustrated, anxious, or distressed by somatic pain or separation. Recently, problems of attachment development in these individuals and their vulnerability to stress have been related by some authors to the behaviour problems and psychopathological features.
(38,39)
Behavioural phenotypes in relation to mental illness
Recently, the concept of a behavioural phenotype has been introduced as an attempt to assess the interrelationship between specific behaviours and genetic disorders (see Chapter 10.4). In addition to speciﬁ  c behaviours, an increased prevalence of

psychiatric syndromes have been reported in association with par-ticular genetic and other syndromes. The possible link between a behavioural phenotype and the particular psychiatric disorder of a person with ID is a highly challenging issue for investigators researching this ﬁ  eld. For further information.
Down syndrome has always been associated with speciﬁ  c patterns 
of language, and cognitive and social development. In most studies, these persons were found to exhibit muted affect and have deﬁ  cient 
language development, and yet they showed particular strengths in socialization. The tendency for such individuals to develop 
Alzheimer dementia has often been described. The occurrence of 
affective disorder among Down syndrome subjects had attracted the attention of scientists recently.
(40,41) Diurnal mood variations,

(40,41) Diurnal mood variations, 
speech reduction, and an increase in aggression are the commonly reported symptoms, which are indicative of depression among per-sons with Down syndrome. The onset of mania in this syndrome has been disputed. However, cases of mania have been reported later in life among those having Down syndrome.
Persons with fragile X syndrome have often been described as 
having autistic-like social impairments. However, among these individuals, social anxiety is more characteristic than social indifference.
(42) In addition, attention deﬁ  cit, stereotyped behav-
iour, self-injury, and hyperactivity are common.
In Prader–Willi syndrome, hyperphagia and obsessive–compulsive

In Prader–Willi syndrome, hyperphagia and obsessive–compulsive 
and aggressive behaviour are common. The occurrence of brief psychotic episodes with heterogeneous symptoms have been described among these persons.
Different behavioural phenotypes and psychiatric disorders have 
also been described for other syndromes. For example, anxiety disorder, sleep disorder, and hyperactivity are common in Williams syndrome, depression is often found in Klinefelter’s syndrome, and self-injurious behaviour occurs regularly in Cornelia de Lange syndrome.
Genetic and environmental factors and 
onset mechanisms
It should be stressed, however, that the very same behaviours may

It should be stressed, however, that the very same behaviours may 
be found among individuals with genetic as well as with idiopathic ID, which probably means that these behaviours are not only the product of genetic factors, and that other factors may be the cause as well. Among other things, the process of psychosocial develop-ment and interactional patterns with the surroundings can affect the onset of a particular behaviour. Apparently, genetic characteris-tics can inﬂ  uence the psychosocial development, which then can be 
decisive for the onset of particular interactional patterns and particular behaviours (so called ‘heightened probability’ , according to Dykens et al .
(43)). The question is: Do these behaviours play a

(43)). The question is: Do these behaviours play a 
role in the onset of the aforementioned psychiatric disorders asso-ciated with these genetically based syndromes, and if so, how do they do this? Or, does a genetic disorder have a more direct role in the onset of a particular psychiatric disorder?
For a better understanding of how speciﬁ  c psychiatric disorders 
evolve among these individuals, it is necessary to make a scheme of the onset mechanisms involved in each psychiatric disorder. It is important to take account of the genetic disorder, the develop-mental processes, and the interaction patterns with the surroundings in which particular behaviours may play an important role. If one takes all these factors into consideration, it may be expected that in certain cases particular psychiatric disorders have a speciﬁ  c aetiology.

An example is self-injurious behaviour, which is currently consid-ered to be a ‘challenging’ behaviour, but, according to various professionals in this ﬁ  eld, warrants being seen as a speciﬁ  c psycho-
pathological phenomenon. However, there are also examples in which the connection between genetic and psychiatric disorder appears to be more direct. An example is the velocardiofacial or Shprintzen syndrome.
(44,45)
Psychiatric problems in older 
persons with ID
In elderly persons with ID, besides dementia, other psychiatric dis-
orders, like psychotic conditions, depression, and anxiety disorders, are common.
(46) In a mixed community and institutionalized 
group of persons with ID older than 50 years, Patel and colleagues(47)
found a prevalence of psychiatric disorders, mainly depression and anxiety in 11.4 per cent of the population. Other authors
(48)

(48)
ascertained that major psychiatric disorders could be found in 20 per cent of persons with ID aged 65 and above. Behavioural symptoms such as aggression and self-injury frequently accompany psychiatric problems among these individuals. Causes for frequent psychiatric problems in this population group are various; like changes in social milieu and living pattern, loss of beloved ones, social deprivation, and inactivation done to retirement from the work or previous activities and medical, in particular neurological, conditions at this age (see Chapter 9.2.1). Frequently, psychiatric disorders in these individuals can be found as an accompaniment of a dementia process. Differentiation between the beginning stage of dementia and other psychiatric disorders can be a difﬁ  cult task.
(49)
In these cases, a total bio-psycho-social picture of the involved per-

(49)
son, including a detailed patient history, as well as an insight into the surroundings circumstances and in interactions is necessary for appropriate understanding of the patient’s symptoms. Use of some assessment instruments can be helpful (see Chapter 10.1).
In principle, the diagnosis of psychiatric disorders in persons with mild ID and good verbal skills does not differ much from diagnos-ing these disorders in persons with average cognitive skills.
(50)
However, in persons on a lower level, the recognition of mental dis-
orders can be difﬁ  cult, partly because of linguistic limitations and 
partly because of difﬁ  culty in distinguishing between behaviour 
problems (challenging behaviour) and symptoms of psychiatric illness. Communication problems often ask for management through another individual (‘management by proxy’), which means

1859
that carers are relied upon to give description of a person’s

behaviour. The diagnostician should know that the reliability and validity of such information may be problematical and, besides this information, should search for more objective sources, like infor-mation through non-verbal communication with the patient and through observation of the patient in different situations and inter-actions. Distinguishing between behaviour problems and psychiat-ric illness is a very important issue for adequate aid. It asks for a multi-disciplinary assessment approach in which experienced (specialized) professionals from different disciplines, participate forming together a multi-disciplinary team. These teams have expertise in both intellectual disability and mental health, and provide direct services to patients and carers. Through the assess-ment of a specialist team, an insight is being obtained whether presenting behaviours of involved individual are the results of an organic condition, a psychiatric disorder, environmental inﬂ  uences,

or a combination of these factors. The clinical symptoms must be viewed in a broad context of a patient’s functioning, considering his/her deﬁ  cits, strengths, and relevant bio-psycho-social factors. 
For example, a disruptive behaviour can be a symptom of a psychi-atric disorder in one person, whilst in another person, and in other environmental circumstances, it may be a means of communica-tion, serving as a vehicle for obtaining a caregiver’s attention or avoiding an unwanted task. Delineation of a subtype of an estab-lished psychiatric disorder asks for the specialist knowledge of the diagnostician.
The specialist teams should be based locally, providing inpatient 
care as well as outpatient and community-based interventions 
(see Chapter 10.9). Involvement of parents and carers as partners in the management plan can have more advantages and is being recommended.
The diagnostic evaluation may require signiﬁ  cantly more time

The diagnostic evaluation may require signiﬁ  cantly more time 
than the evaluation of persons of normal cognition. An accurate diagnosis which integrates all assessment results of the multi-disciplinary team members should serve as a starting point for the treatment.
(51)
Persons with ID are more prone to psychiatric disorders and behavioural problems than the general population. The symptoms of their biological disorders, developmental processes, and interac-tion patterns may give atypical clinical pictures, particularly in individuals with moderate and severe ID. It is probable that certain disorders are speciﬁ  cally associated with or even unique to the ID. 
Traditional nosological classifications do not adequately accommodate the phenomenology of psychiatric disorders in this population. A broader taxonomy, that takes account of the atypical presentation of psychopathology in this population is necessary.

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30. Van Praag, H.M. (2000). Nosologomania: a disorder of psychiatry. 
The World Journal of Biological Psychiatry ,1, 151–8.
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classiﬁ  cation of psychiatric disorders for individuals with 
developmental disabilities. Mental Health Aspects of Developmental 
Disabilities ,6, 26–35.
32. Einfeld, S.L. and T onge, B.J. (1996). Population prevalence of 
psychopathology in children and adolescents with intellectual 
disability: epidemiological ﬁ  ndings. Journal of Intellectual Disability 
Research ,40, 99–109.
33. Achenbach, T.M. and Zigler, E.F. (1968). Cue-learning and 
problem-learning strategies in normal and retarded children. 
Child Development ,39, 827–48
34. Menolascino, F.J. (1977). Challenges in mental retardation: progressive 
ideologies and services . Human Sciences Press, New Y ork.

35. Matson, J.L. (1985). Bio-social theory of psychopathology: a three 
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36. Tanguay, P .E. (1984). T owards a new classiﬁ  cation of serious 
psychopathology in children. Journal of the American Academy of 
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Reinzeniering der Selbstentwertung . Neuerkeroder Forum 4, 
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challenging behaviour in people with severe and profound intellectual disability; a stress-attachment model. Journal of Intellectual Disability

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mental retardation syndromes . Paul Brookes Publ., Baltimore.
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10.5.3 Epilepsy and epilepsy-
related behaviour disorders among people with intellectual disability
Epilepsy is deﬁ  ned as at least one epileptic seizure; this in practice

Epilepsy is deﬁ  ned as at least one epileptic seizure; this in practice 
means two or more epileptic seizures unprovoked by any immedi-ate identiﬁ  able cause during a relatively short period of time. 
Epileptic seizure is a clinical manifestation presumed to result from an abnormal and excessive discharge of a set of neurones in the

1861
brain. An epileptic syndrome is a cluster of symptoms and signs 
including type of seizure, mode of seizure recurrence, neurological ﬁ ndings, and neuroradiological or other ﬁ  ndings of special investi-
gations, customarily occurring together. An epileptic syndrome can have more than one cause or the cause may remain unknown; con-sequently outcomes may be different. Pseudoseizure is used to denote epilepsy-like seizures without concomitant EEG changes.
Epilepsy and intellectual disability are symptoms of brain origin. 
The former is an unstable condition, where during the seizure or ictally the behaviour of a person with epilepsy is abnormal, but between the seizures or interictally there is no affect of epilepsy on his or her behaviour. Intellectual disability is a more or less stable condition. However, the categories of the degrees of intellectual disability are neither absolute nor static, as some children may move up or down between them.

This chapter deals with the diag nosis, manifestations, behavioural 
disorders, frequency, aetiology, treatment, effects of antiepileptic drugs on behaviour, and prognosis of epilepsy in people with intel-lectual disability.
Diagnosis and differential diagnosis 
of epilepsy
The diagnosis of epilepsy is clinical and requires the collection of 
historical data, physical and mental examination, EEG, and labora-tory tests such as determinations of blood glucose and electrolytes.
(1)
In babies with epilepsy, attention should be paid to changes of skin colour or cardiac rhythm, sucking and smacking, which all may be epileptic phenomena. In people with intellectual disability it may be difﬁ  cult or impossible to obtain an accurate clinical history from

the patient. The clinician often has to depend on relatives or other professionals involved in the care of the patient. In addition to a description of the seizures, a history of the age at onset of epilepsy and the complete clinical picture of the epileptic syndrome are of value.
General factors that provoke seizures include fever, infection, 
hypoglycaemia, stress, excessive waking, alcohol withdrawal, hyper-ventilation, some medications, sudden discontinuation of sedative drugs, and speciﬁ  c activity. Fevers associated with infections such 
as those of the ears, sinuses, upper respiratory tract, or urinary tract 
are quite common. If seizures are exacerbated, ensure that any treatable infection is identiﬁ  ed. The situation is further confused

are quite common. If seizures are exacerbated, ensure that any treatable infection is identiﬁ  ed. The situation is further confused 
by the fact that seizures can produce the fever, which, however, resolves within an hour. Withdrawal seizures may be precipitated by a sudden discontinuation of drugs such as benzodiazepines which have an antiepileptic effect, although they may have been prescribed for another reason. Some seizures may be associated with a speciﬁ  c activity, especially if this activity induces excitement 
or anxiety. Exercise-induced seizures occur regularly in some patients.
Many people with intellectual disability have abnormal behav-
iour that resembles epileptic seizures but is not epileptic in origin. The diagnostic and other problems caused by non-epileptic sei-zures or pseudoseizures are well known.
(2) Different dyskinesias,

(2) Different dyskinesias, 
psychogenic attacks, and other non-epileptic episodes may be manifested as pseudoseizures at different ages (Table 10.5.3.1). Sudden aggression and other e pilepsy-like condit ions (T able 10.5.3.2)
are in practice the most important reasons for the overdiagnosis of epilepsy, and consequently also for overmedication and subsequent 
intoxication in patients with intellectual disability. On the other hand, non-convulsive epileptic phenomena and even partial seizures (Table 10.5.3.3) may be difﬁ  cult to diagnose in people with intel-
lectual disability. The situation is more complicated when patients 
with intractable epilepsy have both real epileptic seizures and 
pseudoseizures, for example psychogenic seizures. In such cases the 
recognition of psychogenic seizures
(3) (Table 10.5.3.4) helps to 
identify appropriate treatment.(4)10.5.3  epilepsy and epilepsy-related behaviour disorders among people with intellectual disability

Table 10.5.3.1  Salient non-epileptic episodes at different ages
Age Disorder
0–2 months Tremor
Dyskinesias associated with bronchopulmonar dysplasiaBenign myoclonus during sleepApnoea
2–18 months Paroxysmal torticollins
Ipsoclonus myoclonus syndromeIntestinal obstructionBreath-holding spellsJactatio capitisMasturbationParoxysmal choreoathetosisGastro-oesophageal reﬂ  ux
1.5–5 years Pavor nocturnus
Benign paroxysmal vertigoNodding puppet syndromeEnuresis nocturnusConfusion with feverFamilial dystonic choreoathetosis
5–12 years Tic
Complicated migraineAttention disturbanceSleepwalkingParoxysmalis choreoathetosis
>12 years Vertebrobasilar migraine
SyncopeHyperventilation syndromeObstructive sleep apnoeaPsychogenic attacksRaving ﬁ  ts
Table 10.5.3 .2 Conditions often misdiagnosed as epilepsy in

Table 10.5.3 .2 Conditions often misdiagnosed as epilepsy in 
subjects with intellectual disability
Sudden aggression
Self-abuseBizarre behaviourAbnormal motor activityStaringEye-blinkingNystagmusExaggerated startle
Intermittent lethargy

SECTION 10  intellectual disability (mental retardation) 1862
Using magnetic resonance imaging ( MRI ), it is possible to identify 
structural brain abnormalities, including neoplasms, dysplasia, heterotopia, or diseases in the brainstem and/or posterior fossa. If MRI is not available, CT is recommended.
Prolonged video-EEG monitoring of the patients is of use in 
selecting candidates for epilepsy surgery or in distinguishing between epileptic and non-epileptic seizures. Basically, this enables any behaviour to be analysed in relation to the EEG changes. If this investigation is not available, portable cassette recording of the EEG may also be of considerable value. The diagnosis of subclinical seizures, including minimal behavioural or cognitive changes in the absence of any obvious clinical seizures, can be demonstrated as lengthened reaction times during EEG discharges in the Romny test.
The brain function of people with epileptic seizures and

The brain function of people with epileptic seizures and 
syndromes can be examined by interictal and ictal single-photon emission CT, positron emission tomography, functional MRI, magnetic resonance spectroscopy, and magnetoencephalography together with simultaneous EEG. Such investigations can help to deﬁ ne the epileptogenic brain lesion and thereby guide management 
including decisions about epilepsy surgery.
Epilepsy and epileptic syndromes at 
different ages
The main categories in the classiﬁ  cation of seizures and epilepsy 
are primary generalized seizures, focal seizures, and secondary generalized seizures
(5) (Table 10.5.3.5). The semiologic seizure classiﬁ  cation(6) seeks to provide common descriptive terms for typi-
cal ictal symptoms and for seizure evolution (Table 10.5.3.6). Epileptic syndromes
(7) are quite frequent in people with intellectual 
disability ranging from early infancy through childhood to adoles-

cence (Table 10.5.3.7). As understanding of the pathophysiologic and anatomic substrates of epileptic seizures, syndromes and disor-ders increases, these classiﬁ  cations may need to be reappraised. 
(8–10)
Infancy
Infants with early infantile epileptic encephalopathy  or Ohtahara 
syndrome seem initially neurologically normal, but soon develop increasingly frequent seizures with tonic spasms that resemble infantile spasms and are usually resistant to treatment. Severe pro-gressive intellectual disability becomes evident with age. Many die early and most survivals are handicapped. Some may evolve into the West syndrome and some later into the Lennox–Gastaut syn-drome (see below). The EEG shows a ‘burst suppression’ pattern with an almost ﬂ  at tracing for several seconds, alternating with dif-
fuse, high-amplitude, slow wave-and-spike bursts, poorly modiﬁ  ed

fuse, high-amplitude, slow wave-and-spike bursts, poorly modiﬁ  ed 
by sleep–wake stages.
(11) The aetiology of Ohtahara syndrome 
includes usually congenital or acquired malformations of cortical development and diffuse prenatal encephalopathies, the cause of which remains unknown, so far. A report on a case of Ohtahara syndrome included a metabolic defect with cytochrome oxidase deﬁ ciency.
(12)
Early myoclonic epileptic  encephalopathy is another epileptic 
syndrome occurring during infancy with a grim prognosis.(13) The 
predominant seizure pattern is erratic, paroxysmal, fragmentary myoclonus, often associated with other seizure types. Brain malfor-mations are not so common as in Ohtahara syndrome.
Infantile spasms  occur usually at the ages of 4 to 6 months and 
in 90 per cent of cases during the ﬁ  rst year of life. The events resem-
ble the Moro reﬂ  ex with sudden, brief ﬂ  exion of neck and trunk, 
raising both arms forwards or sideways, sometimes with ﬂ  exion at

raising both arms forwards or sideways, sometimes with ﬂ  exion at 
the elbows, and ﬂ  exion of legs at the hips. Less often, the legs extend 
at the hips. At the early stage ﬂ  exion of the neck may be the only or 
main feature; this may be followed by more complex and dramatic attacks later on. A cry is often associated with the attack either as part of the attack or occurring afterwards as an expression of dis-quiet. The spasms are usually symmetric, but may be asymmetric 
or even unilateral. The EEG is chaotic with slow waves of high volt-
age intermixed with diffuse or asynchronous spikes in both hemi-spheres or in the contralateral hemisphere in unilateral cases. This Table 10.5.3.3  Underdiagnosis of epilepsy in subjects with 
Non-convulsive status epilepticus
Seizures with periodic headacheSeizures with vertigo
Seizures with paraesthesia

Seizures with visceral and vegetative disturbancesLoss of emotional controlPostictal effects
Simple partial seizures
Complex partial seizures
Table 10.5.3.4  Differential diagnosis of epileptic and psychogenic seizures
Typical features Epileptic seizures Psychogenic seizures
Generalized tonic-clonic seizures Complex partial seizures
Comparison of seizures with 
known seizure typesLittle variation in events Wide range of events, but the most 
common are well describedExtremely wide range of events with 
bizarre or unusual behaviour
Ictal EEG Abnormal and changed from preictal Almost always abnormal and changed 
from preictalUsually normal and unchanged 
from preictal
Postictal EEG Almost always abnormal and changed 
from preictalFrequently abnormal and changed 

Effect of antiepileptic 
medication on seizuresProminent, especially in severely 
affected patientsUsually prominent Usually no effect

1863
pattern is called hypsarrhythmia. Infants with unilateral spasms 
need to be examined using a positron emission tomography scan, as contralateral hypometabolism may be due to cortical dysplasia, a condition which may be treatable by resective epilepsy surgery. Aetiology is usually symptomatic including brain abnormalities due to intrauterine infections such as toxoplasmosis, cytomegalic inclusion disease, or rubella. Other aetiologies are brain malforma-tions due to unknown cause. Infants with Down syndrome or tuberous sclerosis may develop infantile spasms. W est syndrome
comprises the triad of infantile spasms, hypsarrhythmia, and intel-lectual disability.
Progressive degenerative brain diseases and neoplasms are rare 
causes of infantile spasms. Also neurometabolic disorders such as 
phenylketonuria, maple syrup urine diseases, non-ketotic or ketotic 
hyperglycinaemia, and urea cycle defects may lead to infantile 
spasms.

spasms.
Severe myoclonic epilepsy  in infants includes generalized or 
unilateral febrile clonic seizures, secondary appearance of myo-clonic jerks, and often partial seizures. All the children affected suffer from intellectual disability from the second year of life onwards. Ataxia, signs of upper motor neurone involvement, and interictal myoclonus may appear. 
(13)
Early childhood
Myoclonic epilepsy of early childhood shares many features with theLennox–Gastaut syndrome .
(13) The latter is a group of epileptic

(13)
(13) The latter is a group of epileptic 
disorders of varied aetiology in childhood. West syndrome often evolves into Lennox–Gastaut syndrome characterized by atypical absences, axial, tonic and sudden myoclonic, atonic, partial, and generalized tonic–clonic seizures, diffuse slow interictal spike waves in the waking EEGs and fast rhythmic bursts (10 Hz) during sleep. A progressive decrease in IQ is often found in children with Lennox–Gastaut syndrome. Myoclonic–astatic epilepsy  or DooseTable 10.5.3 .6 Semiologic seizure classiﬁ  cation
(7)
Aura
Somatosensory auraVisual auraAuditory auraGustatory auraOlfactory auraAutonomic auraAbdominal auraPsychic aura
Autonomic seizure
Dialeptic seizure
Motor seizure

(7)
Aura
Simple motor seizure Myoclonic seizure Epileptic spasm Tonic seizure Clonic seizure Tonic–clonic seizure Versive seizureComplex motor seizure Hypermotor seizure Automotor seizure Gelastic seizure
Special seizure
Atonic seizureAstatic seizureHypomotor seizure
Akinetic seizure
Negative myoclonic seizureAphasic seizure
Reproduced from Commission of Classiﬁ  cation and Terminology of the International 
League Against Epilepsy (1989). Proposal for revised clinical and electroencephalographic classiﬁ  cation of epilepsies and epileptic syndromes. Epilepsia, 30, 389−99, copyright 1989, 
International League Against Epilepsy.Table 10.5.3.5  Classiﬁ  cation of epileptic seizures (International 
League Against Epilepsy, www.ilae.org/Visitors/Centre/ctf/CTF 
table3.cfm, copyright ILAE)
Partial (focal, local seizures)

 With motor signs With autonomic symptoms and signs  With somatosensory or special sensory symptoms: simple hallucinations 
(e.g. tingling, light ﬂ  ashes, buzzing), somatosensory, visual, auditory, olfactory, gustatory, vertiginous
  With psychic symptoms (disturbances of higher cerebral functions): 
dysphasic, dysmnesic, cognitive, affective, illusions, structured hallucinations
  Complex partial seizures (with impairment of consciousness, may 
sometimes begin with simple symptomatology)
 Partial seizures evolving to secondarily generalized tonic–clonic seizures
a
Atypical absencesMyoclonic seizuresClonic seizuresTonic seizuresTonic–clonic seizuresAtonic seizures

a
a Combinations of seizures listed here may occur.10.5.3  epilepsy and epilepsy-related behaviour disorders among people with intellectual disability
Table 10.5.3.7  Salient epileptic syndromes which may be associated 
with intellectual disability and salient intellectual disability 
syndromes which may be associated with epilepsy
Infant
Early myoclonic encephalopathyEarly infantile epileptic encephalopathy with suppression bursts
Infantile spasms
Severe myoclonic epilepsySturge–Weber syndromeDown syndromeFragile X syndromeAngelman syndrome
Epilepsia partialis continua Kojewnikow
Unverricht–Lundborg diseaseLafora diseaseProgressive myoclonus epilepsy with intellectual disabilityOther neuronal ceroid lipofuscinoses
Sialidosis

Myoclonic epilepsy with ragged red ﬁ  bres (MERRF)Rett syndromeLandau–Kleffner syndromeContinuous spike-wave discharge during slow-wave sleep

SECTION 10  intellectual disability (mental retardation) 1864
syndrome  resembles Lennox–Gastaut syndrome, but is not so 
severe.
Later childhood and adolescence
Progressive myoclonus epilepsies  have the nosological picture of 
an evolving syndrome of symptoms including massive and segme ntal
myoclonus, myoclonic or tonic–clonic seizures, partial seizures, cerebellar impairment, and higher neurological dysfunctions. 
(13)
Unverricht–Lundborg disease is most common in the Finnish and North African population, but occur also elsewhere. The disease progresses only over a limited period and stabilizes thereafter. 
(14)
The age of onset is around 7 years and the disease starts with myo-clonus or nocturnal tonic–clonic seizures. The longest lifespans are more than 60 years. The intelligence level is slightly lowered or even normal. Patients with severe intellectual disability have often had drug intoxication. 
(15)
Progressive myoclonus epilepsy with intellectual disability

(15)
Progressive myoclonus epilepsy with intellectual disability 
(Northern epilepsy) and Lafora disease are more progressive disor-ders with different gene defects.
(16) Sialidosis and mitochondrial 
encephalopathy with ragged red ﬁ  bres may also show myoclonic 
seizures. Epilepsy is quite common in girls with Rett syndrome, affecting about 90 per cent of the patients. They may have several seizure types including partial, generalized tonic–clonic, and myo-clonic seizures, atypical absences, short ﬂ  exion or extensor spasms, 
and drop attacks or various combinations of such seizures.
(17)
Of the progressive partial epilepsies , epilepsia partialis

(17)
Of the progressive partial epilepsies , epilepsia partialis 
Kojewnikow or Rasmussen syndrome type 2 is especially impor-tant because the disease is fatal if untreated. The classical model of the association between frequent epileptiform discharges and permanent loss of function is provided by the Landau–Kleffner syndrome or acquired epileptic aphasia. There is increasing evi-dence that frequent epileptiform discharges, perhaps particularly overnight in the form of continuous spikes and waves during slow sleep, also called electrical status epilepticus, is associated with permanent intellectual impairment if allowed to continue for long periods.
(18)
Adulthood and old age

(18)
The proportion of cerebrovascular disorders, brain tumours, chronic alcoholism, and sequelae of brain injuries is increasing with advancing age in the aetiology of epilepsy. From about 35 years of age onwards partial epilepsies become more common than generalized epilepsies. Patients with intellectual disability may also develop these disorders.
Behavioural disorders due to epilepsy
Psychic symptoms may be seen as epileptic manifestations of several epileptic seizure types (Table 10.5.3.5). Thus simple partial seizures may manifest themselves with somatosensory or special sensory symptoms including simple hallucinations such as tingling, light ﬂ  ashes, or buzzing or with psychic symptoms such as dyspha-
sic, dysamnesic, cognitive, affective, illusional, or structured hallu-cinations. Complex partial seizures often include behavioural abnormalities reaching from confusional states to psychotic-like

sic, dysamnesic, cognitive, affective, illusional, or structured hallu-cinations. Complex partial seizures often include behavioural abnormalities reaching from confusional states to psychotic-like 
episodes. This is often the case in temporal-lobe and frontal-lobe 
epilepsies. Among generalized seizures absence status epilepticus resembles psychotic behaviour,
(19) which the person in question 
does not remember afterwards.In patients with intractable seizures, about one-fifth are 
non-epileptic in origin. Patients with psychogenic seizures do not generally have seizures when alone or when asleep. Their EEG shows normal activity preictally, ictally, and postictally. The courses of the psychogenic seizures do not show any uniform pattern as is the case with epileptic seizures (see Table 10.5.3.4). Instead their seizures include a variety of behavioural disturbances including conversion, depressive, anxiety, adjustment, somatoform, psychotic, or facitious disorders.

(2) The antiepileptic drugs are ineffective 
against psychogenic seizures but appropriate psychotherapy is helpful in 70 to 80 per cent of cases. Also panic disorder may be difﬁ cult to distinguish from complex partial seizures especially in 
patients with mild intellectual disability. There exists a relationship between brain damage, epilepsy, ictal, and interictal aggressive behaviour, and socio-economic factors. Rarely, ictal aggression occurs in patients with epilepsy, but postictal confusional aggres-sion, and aggression occurring in postictal psychotic states is more common.
Occurrence of epilepsy related to 
The prevalences of epilepsy and intellectual disability in the general 
population are both close to 1 per cent. Epilepsy is more common and more difﬁ  cult to diagnose and to treat in people with intellec-

tual disability than in those with normal intellect. Population-based studies have revealed that intellectual disability occurs in at least 30 to 40 per cent of individuals with epilepsy,
(20) while the 
prevalence of epilepsy in the population with intellectual disability is about 20 to 25 per cent.
(21) It is higher in the more severely dis-
abled (IQ < 50) than in less severely disabled (IQ 50–70)—30 to 50 per cent and 15 to 20 per cent, respectively. Brain damage tends to be more extensive when epilepsy, intellectual disability, or cerebral palsy are complicated by each other or by other conditions of brain origin. It is unlikely that speciﬁ  c causal factors of epilepsy, 
intellectual disability, or cerebral palsy will ever be positively iden-tiﬁ ed, for these are non-speciﬁ  c clinical features of brain disorder.

intellectual disability, or cerebral palsy will ever be positively iden-tiﬁ ed, for these are non-speciﬁ  c clinical features of brain disorder. 
Epileptic ﬁ  ts themselves, especially if they are persistent, may 
produce brain damage and play a part in producing a progressive decline in the intellectual functioning of patients. Further apparent deterioration of intellectual functioning may be the result of excessively high doses of anticonvulsant drugs.
Epilepsy occurs in all the main aetiological categories of intel-
lectual disability. In a series of 1000 mentally retarded patients, 
epilepsy was less frequent in the prenatal category than in the rest of the series (182/515 or 35.3 per cent versus 260/485 or 53.6 per ce nt). 
Of the main types of epilepsy, partial epilepsy is more frequent in the prenatal and postnatal aetiological categories and in the category of infections and intoxications.
(22)
In people with Down syndrome the frequency of epilepsy is 5

(22)
In people with Down syndrome the frequency of epilepsy is 5 
to 10 per cent. There is an age-related bimodal distribution with about 40 per cent of seizures starting before the age of 1 year and another 40 per cent starting after the third decade.
(23) Roughly 
25 per cent of individuals with fragile X syndrome have epileptic seizures which are usually infrequent, mild, easily controlled, and typically disappear in adolescence, as in benign Rolandic epilepsy. In Angelman syndrome epilepsy is present in more than 90 per cent of the affected individuals.
(23) In Rett syndrome epilepsy 
affects up to 90 per cent of patients(17) Seizures are usually benign

1865
during the early years of life. In patients with aspartylglucosamin-
uria, epilepsy is found in 28 per cent of adults and in 2 per cent of children.
(24) Epilepsy is common (up to 100 per cent) in patients 
with the various forms of neuronal ceroid lipofuscinoses, especially during the last years of life,
(25) and also in other inborn errors 
of metabolism leading to intellectual disability such as sialidosis type 1, Tay–Sachs disease, type 3 Gaucher disease, mitochondrial encephalopathy with lactic acidosis and strokes, and myoclonic epilepsy with ragged red ﬁ  bres.
Aetiology and pathogenesis of epilepsy
The presumed aetiology of intellectual disability is also the pre-
sumed aetiology of epilepsy in most patients.(21,22) In addition, 
patients with intellectual disability may develop an ischaemic or haemorrhagic lesion, a neoplasm, or another lesion in the brain which may lead to epilepsy.
(21) The presumed aetiology of epilepsy

(21) The presumed aetiology of epilepsy 
can be found in about three-quarters of the patients. In the aetio-logical classiﬁ  cation based on the time of the presumed cause of 
epilepsy and intellectual disability, prenatal aetiology is the most common (Table 10.5.3.8). In the aetiological classiﬁ  cation based on 
presumed cause, the categories of unknown prenatal inﬂ  uence, 
infections and intoxications, trauma and physical agents, and other speciﬁ  ed aetiological agents cover most of the cases (Table 10.5.3.9). 
In patients with intellectual disability and epilepsy it is important to try to ﬁ  nd the cause of the intellectual impairment, epilepsy, or 
epilepsy syndrome. In some cases, the epilepsy syndrome or an underlying inborn error of metabolism may be relevant.

Basic mechanisms leading to epilepsy include disturbances in the 
balance between excitatory and inhibitory neurotransmitter func-
tion within brain cells and their connections to important channels 
such as voltage-gated sodium channels. For instance, hyperactivity of the excitatory neurotransmitter glutamic acid and/or hypoactiv-ity of inhibitory neurotransmitter γ-aminobutyric acid ( GABA )
may lead to epileptic seizures. The existence of so many genetically determined disorders leading to intellectual disability and epilepsy
(26)
(Table 10.5.3.10) and the large variation in the prevalence of epilepsy in the speciﬁ  c intellectual disability syndromes and the use 
of new methods such as an array technology suggest that genetic factors play a more important role in producing epilepsy.
The three following examples, as well as those mentioned above,

The three following examples, as well as those mentioned above, 
illustrate  this variety of genetic explanations for epilepsy among intellectual disability syndromes.
(23) Angelman syndrome is a con-tiguous gene defect most often caused by a maternally inherited 
deletion of chromosome 15q11–13. Several of the deleted genes code for GABA receptor subunits. Deﬁ  cits of inhibitory GABAergic 
function could directly predispose affected individuals to seizures. This hypothesis is supported by knockouts of analogous chromo-some region in mice, which produces an epileptic phenotype.
In Down syndrome or trisomy 21 the bimodal distribution of

In Down syndrome or trisomy 21 the bimodal distribution of 
the frequency of epilepsy between young and older ages is interest-ing. The fact that more than 75 per cent of adults with Down syndrome develop late-onset epilepsy coincident with the onset of the neuropathological abnormalities in the brain compatible to Alzheimer’s disease suggests an aetiological role of these abnormal-ities. However, as epilepsy is associated with Alzheimer’s disease in only 10 per cent of patients without Down syndrome, it is unlikely that Alzheimer’s neuropathological abnormalities are solely respon-sible for the late-onset epilepsy in patients with Down syndrome. As the EEG of most of these patients is characteristic of idiopathic generalized epilepsy and the gene for progressive myoclonus epi-lepsy is located in the Down syndrome region on chromosome 21, it is quite possible that this gene product predisposes for a senile 
myoclonus epilepsy in Down syndrome.
(23) Abnormal neuronal

(23) Abnormal neuronal 
circuits with fewer GABAergic neurones in certain cortical layers, cerebral dysgenesis particularly of dendritic spines, pathophysio-logical membrane ion channels, and altered neurotransmitter level are potential mechanisms of epilepsy in Down syndrome.
(23)
In the tandem trinucleotide repeat disorder, fragile X syndrome, 
triplet expansion (CGG) results in shutdown of fragile X intellec-tual disability 1 gene transcription, which may alter overall neuro-logic development and lead to seizures.
(23)
Thus, there exists a spectrum of epilepsy mechanisms among 
these three intellectual disability syndromes, ranging from deletion of a gene or genes that directly leads to hyperexcitability (Angelman syndrome), to a chromosomal triplication that alters several aspects of neuronal development and function (Down syndrome), to a Table 10.5.3 .8 Aetiological classiﬁ  cation of epilepsy and intellectual

disability according to time of presumed cause
N = 129aN = 442b
Prenatal (%) 35.1 41.2
Perinatal (%) 10.0 15.4Postnatal (%) 8.7 18.8Multiple (%) 14.7 4.3Unknown (%) 31.4 20.4Total (%) 100.0 100.0
a Data from Forsgren et al.(21)
b Data from Iivanainen.(22)10.5.3  epilepsy and epilepsy-related behaviour disorders among people with intellectual disability
Table 10.5.3 .9 Aetiological classiﬁ  cation of epilepsy and intellectual 
disability according to presumed cause
N = 442
Infections and intoxications (%) 18.1
Trauma and physical agents (%) 16.3Disorders of metabolism (%) 3.2Gross prenatal inﬂ  uence (%) 24.0Prematurity (%) 0.5Major psychiatric disorder (%) 0.5Psychosocial deprivation (%) 0.0Multiple causes (%) 7.2Hereditary (simple) (%) 0.5Other speciﬁ  ed (%) 19.7Unspeciﬁ  ed (%) 0.0Total (%) 100.0
(Reproduced from M. Iivanainen, Diagnosis of epileptic seizures and syndromes in mentally 
retarded patients. In Paediatric epilepsy  (ed. M. Sillanpää et al.), pp. 233–41. Copyright

retarded patients. In Paediatric epilepsy  (ed. M. Sillanpää et al.), pp. 233–41. Copyright 
1990, Wrightson Biomedical, Petersﬁ  eld)

SECTION 10  intellectual disability (mental retardation) 1866
specific tandem repeat which alters neuronal function in a 
non-speciﬁ  c and probably benign manner (fragile X syndrome). 
It remains to be seen how much dissection of genetic mechanisms underlying other intellectual disability syndromes will provide additional insight into epilepsy mechanisms.
Treatment of epilepsy
The diagnosis of epilepsy and its underlying disorder needs to be made without delay. The identiﬁ  cation and avoidance of provoking 
factors likely to precipitate seizures in each individual is an essential aspect of the overall management. If this is insufﬁ  cient, antiepileptic

factors likely to precipitate seizures in each individual is an essential aspect of the overall management. If this is insufﬁ  cient, antiepileptic 
drug treatment is needed. If this is still insufficient, epilepsy surgery should be considered. Important points to be considered include not only the nature and severity of an underlying disease, but also the degree and location of brain lesion, the age of the patient at onset of epilepsy, and possible pseudodisability (pseudo-retardation) caused by epileptic seizures or by inappropriate medication. It is emphasized that treating frequent epileptiform discharges may not only reverse the intellectual disability which in such cases is pseudodisability or state-dependent intellectual 
disability,
(18) but may also in some cases prevent permanent intel-
lectual disability.
Antiepileptic drug therapy

Antiepileptic drugs interact with each other by three principal mechanisms: enzyme induction, enzyme inhibition, and through altered protein binding. Phenytoin and phenobarbital induce a wide range of enzyme activity. Carbamazepine induces its own enzymatic metabolism, and may induce the metabolism of valpro-ate and phenytoin, resulting in lower concentrations of these drugs. Valproate inhibits the metabolism of phenobarbital and the epox-ide of carbamazepine, resulting in high concentrations of each of these. Lamotrigine is metabolized in the liver. Valproate inhibits the metabolism of lamotrigine, resulting in a longer half-life and higher blood levels of lamotrigine while the blood level of valproate may be decreased. Lamotrigine does not affect the blood level of carba-mazepine. Gabapentin is not metabolized at all and is excreted in the urine unchanged. If levetiracetam is administered with enzyme-inducing drugs, its clearance may increase by 22 per cent, although the drug

Gabapentin is not metabolized at all and is excreted in the urine unchanged. If levetiracetam is administered with enzyme-inducing drugs, its clearance may increase by 22 per cent, although the drug concentrations in serum do not change when using other antiepileptic drugs simultaneously. The free or unbound fraction of antiepileptic drugs is in equilibrium with the brain concentra-tion and is considered to be more relevant than the total blood level. When two drugs with a high degree of protein binding are used together, for example phenytoin and valproate, there may be some displacement of each drug from protein binding, increasing the unbound fraction. This may result in clinical neurotoxicity even when the total (bound plus unbound) blood level is within the reference range. The antiepileptic drugs also interact with many other drugs and may affect their blood levels and action, and vice versa. For instance, chloramphenicol, cimetidine, anticoagulants, ibuprofen, imipramine,

antiepileptic drugs also interact with many other drugs and may affect their blood levels and action, and vice versa. For instance, chloramphenicol, cimetidine, anticoagulants, ibuprofen, imipramine, propranol, and some psychotropic drugs inhibit the metabolism of phenytoin and lead to an increase of phenytoin blood level and possibly to phenytoin intoxication unless the dose of phenytoin is reduced.

Choice of drug
Once the diagnosis of epilepsy has been made, the decision must be made as to whether antiepileptic medication is needed or not. If it is, the most appropriate antiepileptic drug is to be selected. The choice of antiepileptic medication depends primarily on an accu-rate classiﬁ  cation of the seizure type and/or epilepsy syndrome.
Most treatment decisions have to be based on the results of stud-
ies of people who do not have intellectual disability. The exceptions are mainly studies of adults with the Lennox–Gastaut syndrome, where lamotrigine is recommended.
(27) Valproate, carbamazepine, 
oxcarbazepine, and levetiracetam(28) are other antiepileptic drugs 
recommended in generalized and partial seizures based on uncon-trolled studies or consensus. Valproate is the ﬁ  rst choice for gener-
alized epilepsies/seizures, while oxcarbazepine/carbamazepine is the choice for the focal epilepsies/seizures of people with intellec-tual disability.

(29) Dosage and recommended drug levels in blood 
are presented in Table 10.5.3.11. If newer drugs are not available, phenobarbitone, primidone, and phenytoin may be used with cau-tion, if special attention is paid not only to control of seizures, but also to behavioural, cognitive, and cerebellar functions which may Table 10.5.3.10  Genetic diseases with epilepsy and intellectual 
disability
Disease Mode of inheritance Gene location
Progressive epilepsy with intellectual 
disability (Northern epilepsy)AR 8p
Unverricht–Lundborg disease 
(Baltic, Mediterranean)AR 21q22
Infantile neuronal ceroid 
lipofuscinosisAR 1p32
Late infantile neuronal ceroid 
lipofuscinosisAR 11p15
Variant late infantile neuronal 
ceroid lipofuscinosisAR 15q21-23
Juvenile neuronal ceroid 
lipofuscinosisAR 16p12
Finnish variant neuronal ceroid

Finnish variant neuronal ceroid 
lipofuscinosisAR 13q22
Lafora disease AR 6q23-25
Mitochondrial encephalomopathy, 
lactic acidosis (UUR) and 
stroke-like episodes (MELAS)Maternal tRNA-Leu 
(UUR)
Myoclonic epilepsy with ragged 
red ﬁ  bres (MERRF)Maternal tRNA-Lys
Epilepsy and mental retardation 
limited to femalesX-linked Xq22
Tuberous sclerosisa AD 9q34 16p13
Angelman syndromea AD 15q13
Neuroﬁ  bromatosis typea 1 AD 17q11
Fragile Xa X-linked Xq27
Rett syndromea X-linked Xq28-McCP2
AR, autosomal recessive; AD, autosomal dominant.
a Epilepsy and/or intellectual disability may be manifested as part of the phenotype.

1867
be affected adversely, and sometimes insidiously, by these drugs. 
However, it is stressed that because of the lack of well-designed properly conducted randomized controlled trials for patients with newly diagnosed generalized of focal untreated seizures/epilepsies and for children in general, it is impossible at present to develop evidence-based guidelines aimed at identifying the overall optimal recommended monotherapy antiepileptic drug.
(30)
Most antiepileptic drugs may aggravate certain epilepsies. This is 
the case especially with phenytoin and carbamazepine in idiopathic generalized absence and myoclonic epilepsies. Although valproate has low risk of seizure aggravation,
(31) it may cause weight gain, 
polycystic ovaries, and hepatitis. Oxcarbazepine may lead to hypo-natraemia and vigabatrin to visual ﬁ  eld defects.
(32)
Withdrawal of treatment
Withdrawal of antiepileptic medication in patients with intellectual

(32)
Withdrawal of antiepileptic medication in patients with intellectual 
disability needs to be considered, provided their epilepsy is well-controlled and there are no speciﬁ  c contraindications for the with-

drawal. Depending on the type of seizure or epilepsy syndrome and the individual history, it might be worth considering slow reducing the medication after a 2-year seizure-free period. However, if the individual is in a particularly poor prognostic category or if there is a history of severe, prolonged status epilepticus, it is worth waiting for longer before attempting medication reductions. Despite these reservations, attempts to discontinue antiepileptic medication in people with intellectual disability can be successful. It would appear that a better likelihood of a successful outcome may be suggested by later onset of epilepsy, i.e. after 2 to 2.5 years of age, a shorter duration, lower antiepileptic drug levels, and normal EEGs, together with complete control of the seizures.
(33) The risk of recurrence of

(33) The risk of recurrence of 
the seizures also depends on the type of epilepsy.(34) In complex partial seizures, where exogenic factors are more signiﬁ  cant than 
genetic ones, the prognosis is good after 2 to 4 seizure-free years. The prognosis is worse in simple partial seizures, or in absence sei-zures with tonic–clonic seizures and grand mal tonic–clonic seizures, and at least four seizure-free years are recommended before ceasing medication. Patients with juvenile myoclonic epilepsy, or absence seizures with clonic–tonic–clonic seizures or grand mal clonic–tonic–clonic seizures, may need to take long-term, even lifetime medication. The relapse rate is likely to be high, even if these patients have been free of seizures for several years.
Status epilepticus

First-line treatment of status epilepticus is usually with intravenous benzodiazepines, either diazepam or lorazepam. If this is not effec-tive, then intravenous phenytoin or intravenous or intramuscular fosphenytoin is recommended. Rectal paraldehyde may be of value in children. Rectal diazepam has been the pre-hospital treatment of ﬁ rst choice because it can be administered by non-medical personnel. 
A history of status epilepticus is liable to inﬂ  uence decisions about 
withdrawing regular antiepileptic medication. It would be wise to proceed with caution, ensuring that any recurrence of status epi-lepticus can be treated readily, if withdrawal of regular medication is to be undertaken.
Epilepsy surgery

Frequent severe epileptic seizures despite treatment with adequate antiepileptic medication for about 2 years means that epilepsy surgery needs to be considered. In addition there are certain disor-ders such as Sturge–Weber syndrome or unilateral infantile spasms where epilepsy surgery may be of beneﬁ  t during infancy. The treat-
ment of choice in children with Rasmussen syndrome type 2 currently is hemispherectomy, which needs to be done as early as the diagnosis is clear. Difﬁ  culties in cooperation and minimal 
psychosocial gains due to low IQ as well as progressive underlying disease may be contraindications for epilepsy surgery. The preop-erative consideration includes extensive examinations such as video-EEG monitoring, high-resolution MRI, positron emission tomography, and neuropsychological and psychiatric evaluation according to the generally accepted principles.
(35) The goal is to 
select those candidates who will beneﬁ  t from epilepsy surgery.

select those candidates who will beneﬁ  t from epilepsy surgery. 
Surgical outcome varies according to the different pathologies of epileptogenic lesions. Thus, the results of surgery are better among patients with mesial temporal sclerosis, chronic encephalitides, infantile hemiplegia, focal cortical dysplasia, tuberous sclerosis, Sturge–Weber syndrome, or post-traumatic cicatrix than among 
patients with extratemporal focal sclerosis, polymicrogyria with or 
without heterotopia or hemimegalencephaly, anoxic brain damage, gliosis of obscure aetiology, or no structural pathology.
(36) All these 
ﬁ ndings must be taken into account when selecting patients with 
epilepsy and intellectual disability for epilepsy surgery. As onset of intractable epilepsy within the ﬁ  rst 24 months of life is a signiﬁ  cant 
risk factor for intellectual disability, early intervention for epilepsy surgery is emphasized.
(37)
Behavioural disorders caused by antiepileptic drugs

(37)
Most antiepileptic drugs may also cause behavioural disturbance and cognitive dysfunction.
(38) For example, the diplopia caused by 
carbamazepine may result in considerable distress and consequent behavioural disturbance. Communication difﬁ  culties, which are Table 10.5.3.11  Pharmacokinetic properties of antiepileptic drugs
Drug Dose (mg/kg/day) Doses per day Therapeutic range
(μg/ml) (μmol/ml)
Phenobarbitone 1–3 1 10–30 40–130
Primodone 10–15 2 or 3 6–12 25–50Phenytoin 4–6 1 or 2 10–20 40–80Carbamazepine 15–20 2 or 3 4–12 15–50Oxcarbazepine 15–40 2 or 3 15–23 30–120
a
Valproate 15–30 2 or 3 50–100 300–700Ethosuximide 15–30 1 or 2 40–100 280–700Levetiracetam 20–40 2 5–65 30–370Vigabatrin 40–100 1 or 2 NA NALamotrigine 2–4(10)
b1 or 2 NA NA

a
b1 or 2 NA NA
Gabapentin 20–40 3 NA NATopiramate 400 3 NA NATiagabine 32–56 3 NA NAClonazepam 0.01–0.2 2 or 3 20–75 60–240
NA = not available.
aFor monohydroxy derivative.
bWith enzyme-inducing drugs.10.5.3  epilepsy and epilepsy-related behaviour disorders among people with intellectual disability

SECTION 10  intellectual disability (mental retardation) 1868
common in intellectually disabled patients, may add to the distress 
and make behavioural disturbance more likely.
Intellectually disabled people with epilepsy are especially 
vulnerable to harmful neurotoxic effects—sedation caused by phe-nobarbital or benzodiazepines or cognitive and cerebellar dysfunc-tion caused by phenytoin alone or often together with other anti-epileptic drugs. If these alarming effects are not taken into account, inappropriate medication may even jeopardize the rehabilitation of the patients.
Uncertainty about the long-term effects of antiepileptic drugs on 
brain function and development is largely due to conﬂ  icting results 
of often biased human observations. The problem can only be resolved in controlled experiments which by necessity must be done in animal models. Behavioural and structural consequences of epileptic activity and their modiﬁ  cation by antiepileptic drugs

are important points to be evaluated in experimental studies. It was reported
(39) that enhancement of GABAergic inhibition by admin-
istration of vigabatrin prevented both pyramidal cell damage in CA1 and CA3 areas of hippocampus and the disappearance of somatostatin immunoreactive neurones from the dentate gyrus after perforant path stimulation in rats. Furthermore, the preserva-tion of hippocampal structure was accompanied by prevention of the spatial memory deﬁ  cits seen in control animals after such 
stimulations. Another study using a kainic acid status epilepticus model in adolescent rats
(40) showed that animals that received

(40) showed that animals that received 
kainic acid followed by valproic acid resembled control animals who had never received kainic acid with respect to their behav-ioural and memory performance and had fewer histological lesions. Animals that received kainic acid followed by saline or phenobarbi-tal had impaired learning and behaviour, and more extensive lesions in the hippocampus. Thus, in this experiment valproic acid suppressed seizures and subsequent epilepsy while phenobarbital was only partly effective in suppressing seizures and did not pre-vent epilepsy. It is likely that seizures themselves, as opposed to the drugs, produced negative behavioural consequences in these rats. It is noteworthy that valproate at very high doses was protective against neuronal damage and prevented epileptogenesis in the kainic acid model.
Chronic phenytoin intoxication, especially in multiple drug

Chronic phenytoin intoxication, especially in multiple drug 
therapy, may lead to ataxia, balance impairment and in the worst case ﬁ  nally to persistent loss of locomotion.
(41) Another example of 
an insidious and dangerous effect of phenytoin was documented by the changed course of Unverricht–Lundborg disease. Its rather benign course worsened during phenytoin treatment, so that the patients became bedridden and pseudoretarded and their lifespan shortened from 50 to 60 years to under 30 years. When these patients were treated with valproate instead of phenytoin, their lifespan increased to the prephenytoin level.
(15) In some of these 
patients, the loss of locomotion was reversible after valproate replaced phenytoin.
Prognosis

Prognosis
The long-term outcome of patients depends primarily on the underlying disorder; prognosis is better in idiopathic than in symp-tomatic cases. If it is not a question of a progressive brain disorder, epilepsy is quite easily treatable in patients with intellectual disability. Thus, about 70 per cent may obtain good seizure control with appropriate antiepileptic drug therapy or epilepsy surgery. The outcome of patients with speciﬁ  c disorders may vary consider-
ably. For instance, the outcome of patients with Doose syndrome is variable but basically better than that of patients with Lennox–
Gastaut syndrome. If hemispherectomy is not undertaken in time in Rasmussen syndrome type 2, the course of the disease, including neurological deﬁ  cits, other types of seizures, and mental impair-
ment is progressive.
Epileptic seizures themselves, and frequent epileptiform dis-

charges, may produce brain damage and play a part in producing progressive decline in the intellectual functioning of patients
(18)
probably through at least two mechanisms: excitatory glutamate storm within cerebral neurones
(42) and opening of the blood–brain 
barrier(43) during and after epileptic seizures.
Sleep disorders are often associated, in people with intellectual dis-
ability, with difﬁ  cult-to-treat epilepsy and behavioral problems.(44,45)
When sleep disorders are diagnosed and treated, antiepileptic and 
also psychotropic medication can be reduced successfully.
The quality of life in this population beneﬁ  ts from early diagnosis 
and differential diagnosis of epilepsy, including epilepsy-related behavioural disorder in patients with intellectual disability, identi-ﬁ cation of its aetiology, and appropriate antiepileptic drug treat-

ment using ﬁ  rstly one drug therapy and, if needed later, rational 
multiple drug therapy. Currently, valproate is the ﬁ  rst choice in 
generalized seizures while oxcarbazepine or carbamazepine are used for partial seizures with or without secondary generalization. Broad-spectrum drugs such as levetiracetam, lamotrigine, topira-mate, or zonisamide are promising. The usefulness of epilepsysurgery should be considered in intractable cases no later than within 2 years, if adequate antiepileptic drug therapy does not help. T o minimize sedative and other behavioural and other side-effects caused by antiepileptic drugs the fewest possible drugs should be 
administered at the lowest effective dose. This means that there should be careful clinical observation of the patients together with

administered at the lowest effective dose. This means that there should be careful clinical observation of the patients together with 
determination of drug concentrations in blood and other appro-priate laboratory tests. Psychological aspects and sleep behaviour of the patients need to be taken into consideration in the treatment of epilepsy in patients with intellectual disability. Doctors and other personnel working in this ﬁ  eld need special education.
Future prospects in the treatment of intractable epileptic
seizures might involve the development of gene therapy, neuro-protective drugs, and drugs targeting epileptogenesis. Such treat-ment possibilities may bring new hope for people with epilepsies that are difﬁ  cult to treat, including the population with a high 
proportion of refractory cases, namely that with intellectualdisability.
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disorder and epileptic phenomena: clinical aspects of the comorbidity. Epilepsia ,47(Suppl. 5), 78–81.

10.6
Methods of treatment
The presence of intellectual disability (mental retardation) affects 
the character of treatment in a number of ways.
1 Limited communication will hamper diagnosis so that much 
more has to be inferred from observable behaviour and greater weight given to the interpretation of carers.
2 Diagnosis is provisional, a therapeutic hypothesis that provides 
the basis for a programme of treatment that is, essentially, a therapeutic trial. There is a wide variation in individual charac-teristics, with intellectual disability (mental retardation) extend-ing over an enormous range of ability, associated disabilities, aetiology, and psychopathology. Multiple pathology means that the response can be unexpected and ambiguous. For example, diminished aggression with carbamazepine may simply reﬂ  ect

its psychotropic effect but may also be the result of better control of unrecognized epilepsy. A well-designed behavioural milieu may produce a rapid improvement in disturbed behaviour. However, the improvement might simply reﬂ  ect the effect on 
someone with autism of moving to a more settled, structured, and predictable environment. It may also reﬂ  ect an improvement 
in organic disorder (such as epilepsy or gastritis) in response to a reduction in stress. The therapist has to tailor the treatment to the individual, to try to be speciﬁ  c as to what aspect of the disor-
der is being targeted and be very selective as to whom they treat.
3 Ill-deﬁ  ned treatment objectives often leave it unclear whether a 
treatment is aimed at a disorder (e.g. autism), a symptom (panic), or an associated disorder (depression or epilepsy).
4 Normal developmental change may be misattributed to a coinci-

dent treatment programme. For example, autism and epilepsy often show spontaneous improvement at about 4 years age and again in late adolescence, both times when the person is likely to be moving into new programmes. This propensity for matura-tional improvement, coupled with a tradition of care, has led developmental psychiatrists to have a greater therapeutic opti-mism for many problems, such as personality disorders, that are 
often considered intractable in those of normal ability.
5 Natural cycles of change can give a misleading sense of success. 
For example, a behavioural programme may be credited with the remission of a self-limiting episode of disorder such as depression. The true diagnosis may become clear only when it recurs and 
fails to respond to booster programmes.

6 There is limited evidence for the effectiveness of most treatments. 
Except for the behavioural therapies, most treatment is based on 
small series, open trials, the theoretical, and the ideal.
7 A large component of the therapeutic relationship is indirect, 
being with the family, carers, or professionals rather than directly with the patient. Many programmes utilize the power of the placebo effect, a dynamic that confounds scientiﬁ  c trials but one 
that should be used to its full in everyday clinical practice. 
Limited communication and greater dependency lead to work 
with the systems around the patient; many of the approaches, such as family therapy, deriving from child psychiatry.
8 The ability to consent to treatment is often underestimated. 
Circumstances often make it difﬁ  cult for people with mental 
retardation to choose or refuse a particular therapy, particularly behavioural programmes and drug treatments. Their capacity to

retardation to choose or refuse a particular therapy, particularly behavioural programmes and drug treatments. Their capacity to 
give or withhold consent should be assessed automatically and 
their care should fall within a legal framework that safeguards their rights and protects them from abuse.
Treatment services for people with intellectual disability (mental 
retardation) have two components. There is the routine support that should be available to all with intellectual disability (mental 
retardation). Its aim is to help people to grow up as normally as 
possible, offsetting the effects of their disability, and to establish the therapeutic environment. Second is the provision of treatment for individuals with disturbance; aimed at speciﬁ  c symptoms or disor-
ders based on a multiaxial diagnosis
(1) that includes the following:

◆ Axis I: The nature and degree of intellectual disability (mental retardation) for, in addition to the overall developmental delay other, speciﬁ  c, disabilities, and abilities are often present. For 
example, a discrepancy between receptive and expressive language may result in someone understanding little of what is said to him while sounding falsely ﬂ  uent.
◆ Axis II: The aetiology of the retardation—there is increasing 
recognition of the contribution of a behavioural phenotype. Of particular note are autism and its imitators, drawing on the ubiquities of social impairment, obsessionality and communica-tion problems, which are being teased apart.

SECTION 10  intellectual disability (mental retardation) 1872
◆ Axis III:
• Level A: Other developmental disabilities that are associated 
with intellectual disability (mental retardation) such as autism, 
attention deﬁ  cit disorder, and epilepsy,
• Level B: Psychiatric disorder—the way this is deﬁ  ned will 
deﬁ ne the mode of treatment. A functional analysis with ante-
cedents, triggers, and consequences leads into a behavioural pro-
gramme. A more biological label (such as psychosis) opens the 
door to drug treatment. They are not mutually exclusive,
• Level C: The patient’s personality—this is often unusual and it 
may be difﬁ  cult to distinguish from a pervasive developmental 
disorder (see Chapter 9.2.2) which runs through Intellectual dis-
ability (mental retardation) and which, once recognized, often 
explains the inexplicable,
• Level D: Other disorders such as habit disorders and sexual 
preference disorders,
◆ Relevant comorbid, physical conditions such as hay fever,

◆ Relevant comorbid, physical conditions such as hay fever, 
asthma, hypothyroidism, or gastro-oesophageal disorders. 
Particularly important are epilepsy and the antiepileptic agents 
that are dealt with in detail elsewhere (see Chapters 6.2.6 and 
10.5.3, respectively).
◆ The patient’s environment which includes not just their physical 
surroundings but also the people and their relationships with 
them.
◆ Contributory factors from the patient’s past, notably the various 
forms of abuse.
The therapeutic environment
Support may be provided in different ways:
◆ Level A: General, the network of care provided for people with 
a intellectual disability (mental retardation) and their carers. 
This will include community teams, special schools, and the spe-
cialized residential placements that might be resorted to either as 
a short break or as a long-term home.

◆ Level B: Speciﬁ  c to a particular disorder, parental support groups 
exist for autism, epilepsy, and speciﬁ  c forms of intellectual dis-
ability (mental retardation) such as Prader–Willi, Fragile X, and 
Cornelia de Lange syndromes.
A primary aim is to integrate people into their community as far 
as possible. The concept of normalization implies that services 
should avoid the demarcation that leads to adverse discrimination. 
Conversely, those with disabilities too severe or too complex for 
their families or standard teaching or occupational placements may 
fare better in specialist settings. Examples of these are as follows:
◆ Some of those with autism, who are so distracted by the com-
plexity of everyday life and the unpredictability of people that

plexity of everyday life and the unpredictability of people that 
they need specialist environments which are well structured, 
predictable, and under their control.
◆ Those with severe or intractable seizures.
◆ Those with aggressive or disinhibited behaviour so disruptive as 
to block the progress of their peers.
The specialist setting encourages mutual support for people 
and families with similar problems; the staff gain experience; and it allows a concentration of expertise. However, it also encourages 
stigmatization and there is the risk that, in a group, disturbed people 
may copy or amplify each other’s behaviour.
The family and other carers
Disturbance arises in the setting of a system of care which includes 
not only the family but also the staff of other placements, whether 
day or residential, educational or occupational. Its management

day or residential, educational or occupational. Its management 
will depend on the way these people perceive mental retardation 
and its care, their attitudes deriving from both past experience 
and present relationships (Fig. 10.6.1). A great deal depends on 
the extent to which they feel supported and assured in their 
roles, as much by each other as by the available system of care. For 
example, a mother or a teacher who is told frequently that, what-
ever it was that went wrong, it was her fault, is unlikely to cope 
conﬁ  dently.
Disability and disturbance both hinder normal developmental 
experience; the child’s atypical response spoiling the carers’ efforts 
to learn parenting skills and leaving them demoralized or deskilled. 
They may need formal teaching in such skills as how to engage 
socially with the child, to play with them, to give clear and under-

standable instructions, and how to divert rather than confront. 
Disturbance may reﬂ  ect boredom and be reduced simply by increas-
ing the amount and variety of activities. Any approach must take 
a broad view, for carers have to work together comfortably enough 
to be consistent over time. A treatment programme may have to 
address the relationship between the carers as well as their needs. 
This may be sufﬁ  cient in itself, improvement in the patient following 
an overall improvement in functioning in the family, school, or resi-
dential placement. There has been a growth in the conscious appli-
cation of a systemic approach to work in this ﬁ  eld.(2)
Fig. 10.6.1 The start of disturbance: factors inﬂ  uencing behaviour.

1873
Education
This forms the core of any treatment programme, the individual 
getting formal instruction in the skills which others acquire in passing. T eaching and training are lifelong processes, invoking teacher–student relationships, and take place within a structured framework, essential for those students who have difﬁ  culty in 
understanding their environments. The difﬁ  culty is to gauge the 
degree of structure required: too much and the relationship risks becoming a battle about control, easily turning into trench warfare; too little and the student is distracted and learns little. It is a bal-ance that shifts over time, promoting the student’s self-control and autonomy.
(a) Independence and self-help skills
These include the basic skills of everyday life, such as feeding, dressing, or managing stairs or, at a higher level, the use of public transport, how to care for clothes, shop, and budget. Acquiring these, gives a sense of achievement and conﬁ  dence as well as of

increased independence.
(b) Communication skills
The frustration of living in an uncomprehending world frequently contributes to disturbance as the person falls back on various forms of attention seeking or violent behaviour to get their message across. Easier and more effective means of communication may range from simple gestures (e.g. pulling at the trousers to show the need for toileting), through a system of pointing to symbols or pictures, to complex signing which can convey abstract concepts such as emotional states. Language may be verbal or non-verbal and both modalities are taught simultaneously, reinforcing each other so that a course in signing can improve speech. Whatever the system used, it depends on, and will be limited by, the extent to which those around can understand it.
(c) Social and sexual relationships

People are vulnerable to exploitation until they learn the distinc-tion between an acquaintance and a friend. Relationships become complicated by sexual behaviour, hedged around with cultural rules which vary between families making it an especially difﬁ  cult 
area to teach and therefore tempting to ignore. Occasionally sexual arousal drives disturbance in someone for whom masturbation is inefﬁ  cient, physically damaging, unlearned, or forbidden. Wider 
discussion can bring out strongly held beliefs and family conﬂ  icts 
which had been unsuspected or denied until then. This may lead on to other areas requiring resolution, such as whether a person with intellectual disability (mental retardation) should have a sex-ual relationship, marry, or have children.
Out-of-home placement

As described earlier, a move out of the home can be seen either as part of the wider programme of support and social d evelopment or else as part of the treatment of a speciﬁ  c disorder: the distinc-
tion is often blurred.
(a) Support
Short breaks allow individuals and their families some relief from the uninterrupted intimacy of care. They also widen social networks and pave the way towards the eventual departure from home, something that is ideally planned as part of an increasing, adult autonomy. Frequently however, this is left until there is a crisis, for example when the person’s behaviour or dependency has out-
stripped their family’s resources, too often the result of parental inﬁ rmity or death. At this point the unfortunate individual may 
ﬁ nd themselves in a series of short break (or even treatment) place-
ments until something long-term can be arranged.
Placement for educational needs (e.g. in a residential school or

Placement for educational needs (e.g. in a residential school or 
college) becomes necessary where the person’s disabilities (e.g. autism or intractable epilepsy) require specialist skills and settings. It can also be a compromise with a parent who, unable to care for their child themselves, will not accept more standard forms of social care.
The threshold for admission for assessment and treatment will depend on the extent of the supportive service available in the community and is often:
1 For the treatment of more complex disorders such as epilepsy or 
psychosis.
2 For the assessment of disturbance where it is difﬁ  cult to disen-
tangle the relative contributions of innate from environmental factors. For example, a patient’s behaviour may be ampliﬁ  ed by

tangle the relative contributions of innate from environmental factors. For example, a patient’s behaviour may be ampliﬁ  ed by 
an exasperated or exhausted family, particularly where disturbed nights have left them short of sleep. This sets off a secondary, self-perpetuating cycle of disturbance involving the whole house which makes it impossible to discern the underlying, primary disturbance. The cycle may only be interrupted by changing the patient’s circumstances, either by moving staff into the home or by moving the patient out.
3 For the management of behavioural disturbance where:
(a)  The carers are unable to cope—the more frequent reasons 
include:
◆ marital disharmony
◆ the carer’s inability to manage others simultaneously, for example single parents who have several children or a home with several disturbed children
◆ the loss of resilience in a demoralized carer

◆ an adverse or hostile neighbourhood where the carer has to give way in case the patient becomes so noisy that the neighbours complain, or where the patient is bullied or led astray.
(b)  There has been a failure of earlier therapeutic trials with a 
family locked in their pattern of behaviour.
(c)  The patient is at risk of harm.
(d)  The patient presents a s ubstantial risk to others, for 
example, of violence or sexual offending.
(e)  There is the need for effective control of the patient with 
clear limits to disturbed behaviour.
Treatment methods
Discomfort is a potent and frequent cause of disturbance. Because the person may have difﬁ  culty in identifying and localizing pain,

Discomfort is a potent and frequent cause of disturbance. Because the person may have difﬁ  culty in identifying and localizing pain, 
let alone communicating symptoms, it is frequently missed. It is essential that it is a matter of routine to seek and treat common ailments such as hay fever, toothache, earache, dyspepsia, and gastric 10.6 methods of treatment

SECTION 10  intellectual disability (mental retardation) 1874
reﬂ ux. The last of these is particularly associated both with severe 
retardation and with certain disorders such as Cornelia de Lange syndrome as well as an increased possibility of oesophageal carcinoma.
(3) The more severe the degree of disability, the greater 
the need for an active programme of health care.(4)
Intellectual disability’s communication barrier has led to an empha-sis on observable behaviour rather than on reports of subjective emotions or perceptions. Although the function of a behaviour is often misinterpreted, the ﬁ  rst, unthinking response is often a 
behavioural programme. At the same time, increasingly sophisti-cated and more solidly research-based than other forms of psychi-atric treatment, such a programme can produce profound and rapid change.
(5) Programmes are divided broadly into two areas:
1 T eaching appropriate habits and skills which can range from

1 T eaching appropriate habits and skills which can range from 
basic skills such as dressing, continence, communication, and sleep, through to the more sophisticated training in social skills, dating skills, and assertiveness.
2 The unlearning of other, maladaptive forms of behaviour.
These two areas are complementary—it is more effective to 
replace an undesirable behaviour than simply to remove it. Operant, incentive programmes dominate much institutional and offender work. While punishment techniques can be effective and in certain, very unusual situations may be justiﬁ  ed, there must be concern 
about their effect on the trainer as much as on the patient and they need close, ethical control.
(6)

(6)
Behavioural principles can be used to target thought as well as behaviour. With disability comes a tendency to a polarized percep-tion of the world—people seeing themselves either as acceptable, competent, and successful or else as worthless failures; similarly, others are seen as all good or all bad. Cognitive therapy is usually used with people in the mild or borderline range of retardation, and has a particular importance in the treatment of sex offenders, although there are some examples of work with non-verbal people or those with severe intellectual disability. Indeed, where problem-solving skills are formally taught, the improvement may be greater in people with moderate than with mild intellectual disability, sug-gesting some form of ceiling effect to their acquisition. Furthermore, performance may have more to do with the type of problem than with formal measures of ability.
(7)
Rational emotive therapy, developed in an educational setting,

(7)
Rational emotive therapy, developed in an educational setting, 
seeks to change the perceptual set and thereby the impact and inﬂ uence of events on the person. Its background in education 
resulted in a didactic format, giving the therapist a directive role. The orientation is behavioural, focusing on the development of skills, and it lends itself to being taught to groups. A number of open studies of people with moderate and mild intellectual disability have shown it to decrease irrationality and anxiety, and to increase internal control and self-esteem.
(8)
Anger management was developed with people of average ability 
but now has a well-established place in intellectual disability.(9)
Therapy has to cope with a number of obstacles including:
1 The inherent nature of anger which means that the problem is an 
excessive response rather than a deviant one. In this population organic factors are frequent, particularly brain damage, epilepsy, 
and medication.

2 Its usefulness where there is limited communication or more 
severe disability which, combined with personality factors, can make therapeutic engagement difﬁ  cult.
3 The degree to which habitual use has made anger an entrenched 
response.
4 The emotion of anger can be difﬁ  cult to distinguish and label, 
particularly where autism is a component. Here an aggressive response may be the result of excessive anxiety, often amounting to panic.
A programme of anger management may take place at several 
levels.
1 General clinical care—strategies to reduce anger which include 
ensuring that the person feels well, that their physical and social environment is suitable, and that there are suitable occupational and recreational programmes.
(10)
2 Anger management—information is given to help the person

(10)
2 Anger management—information is given to help the person 
recognize anger, its nature, the signs, and consequences, as well as ideas and information about changing their behaviour. This uses a more didactic group instruction which is general and involves less disclosure and engagement by the individual.
3 Anger treatment—an individually tailored programme which 
targets change in cognitive perception, autonomic arousal, and behaviour. Individual engagement is essential and transference and countertransference are important and likely to evoke dis-tressing emotions.
Another target is anxiety reduction through treatments that range, 
depending on the degree of disability, from formal relaxation training through to physical activity. Some do not measure up to their pro-moter’s promise and may even have a detrimental effect,
(11) endors-
ing the principle of treatment as an individual therapeutic trial.
Psychodynamic therapies

Although we have moved away from the early belief that intellec-tual disability itself was the result of emotional abuse and psycho-logical disturbance, we are beginning to recognize the extent to which these factors can reduce adaptive functioning and amplify a cognitive disability. Psychotherapy can complement educational programmes to produce someone who, although no more intel-lectually able, is more mature emotionally and better able to cope with the tasks of everyday life. However, the field is poorly researched so that its efﬁ  cacy is uncertain.
(12)
Both the family and the individual have to adjust to disability; 
a process akin to a series of grief reactions through which people come to terms with the loss of normality.
(13) The process of adjust-

ment occurs as a series of crises triggered by events such as the point of initial diagnosis, the failure of initial treatments, educa-tional assessment and specialized placements, puberty, and leaving home. Each stage brings home afresh the degree and signiﬁ  cance of 
the child’s disability.
The therapist may require speciﬁ  c training and supervision in 
adapting standard approaches to cope with a number of potential elements peculiar to intellectual disability:
1 The therapy is likely to have to deal with the core themes of loss 
and disability.

1875
2 Communication will be limited in various ways and there may 
be unexpected, conceptual barriers. For example, the patient may not understand or even notice gestures, facial expressions, and different tones of voice. They may be unable to identify many emotions, label them, or form abstract concepts. Communication has to be at the patient’s level, being concrete and using simple words, short sentences, and their colloquial or slang terms as well as allowing sufﬁ  cient time for the patient to process the thought. 
The therapist may circumvent some of these barriers by using alternatives modalities, such as music, art, play, and drama.
3 The patient may have a limited and distorted understanding of

3 The patient may have a limited and distorted understanding of 
the roles and relationships of the people around. Unable to appreciate either that the therapist’s knowledge is restricted or that they occupy a different world, the patient may assume that they know all about the patient’s setting and routines. This means that, in order to make sense of what is said, the therapist must learn something of the patient’s background.
4 A combination of memory problems, obsessionality, or poor 
executive function means that there may be repetition of infor-mation, ideas, and conclusions, often given as if they have never been mentioned before.
5 Many people have had lives marked by short and changing rela-
tionships and a nomadic change of accommodation. Engagement in therapy can be difﬁ  cult with a disconcerting readiness to dis-
engage.

engage.
6 Confidentiality may be difficult to establish for someone 
where dependency and total care has discouraged privacy. Carers frequently expect to be told what happens in therapy and the relationship may be complicated by a disclosure that can range from poor care to frank abuse.
Psychopharmacological treatments
Drugs are widely used in intellectual disability. Besides being used for the medical disorders which are more frequent in this population, such as epilepsy, T ourette syndrome, and attention deﬁ  cit disorder,

drugs play a part in the management of a wide range of symptom-atology which includes symptoms as varied as aggression, self-injury, outbursts of distress, compulsive routines, and social withdrawal. A recurrent criticism is that a drug may be used for a purpose other than that suggested by its classiﬁ  catory label (e.g. that antipsychotics 
and antiepileptics are used for conditions other than psychosis or epilepsy, respectively) or that they are prescribed outside their man-ufacturer’s licence. While this often is simply semantic, there must be concern at the level of prescribing of psychotropic drugs.
(14) The 
prevalence and number of drugs being prescribed is associated with, the degree of retardation, and the presence of autism; it is no less in the community than in inpatient institutions;
(15) and is only reduced 
by a determined programme of rationalization.
The presence of intellectual disability colours prescribing:

1 Non-compliance usually results from an unpalatable formula-
tion or a carer’s prejudice rather than forgetfulness.
2 Coexistent disorders, as wide-ranging as epilepsy, constipation, 
and cerebral palsy, can make a patient more vulnerable to adverse effects.
3 Cerebral dysfunction may cause more frequent atypical responses, 
sensitivity being either increased or decreased to various aspects of the drug’s effect. Most of these are dose-speciﬁ  c, paradoxical

sensitivity being either increased or decreased to various aspects of the drug’s effect. Most of these are dose-speciﬁ  c, paradoxical 
effects for therapeutic windows are frequent and, as frequently, forgotten. Prescribing details are subject to revision and should be checked with a current formulary but treatment should be started at a lower dosage and increased more gradually than is generally recommended. The unexpected should be expected so that, besides the routine warning of adverse effects, carers should be able to contact someone if they are in any doubt about the drug’s effects.
4 Evidence of efﬁ  cacy is largely anecdotal, with trials being mostly 
small, open, and uncontrolled, but providing some justiﬁ  cation

small, open, and uncontrolled, but providing some justiﬁ  cation 
for almost any neuropharmacological adventure. The informa-tion that needs to be weighed up is more complex and is there-fore less likely to be within the patient’s capacity to decide whether to take it. This leaves the prescriber with a greater responsibility to put the patient’s interests ﬁ  rst.
(a) Neuroleptics
These are used frequently and for a variety of symptoms despite a 
shortage of consistent, demonstrable, and speciﬁ  c effects. For 
example, although a series of studies have shown haloperidol to be effective in autism, the response can be in any of a variety of areas including improved discrimination learning, a reduction in over-activity, anger, and in the frequency and intensity of outbursts.
(16)
A number of reports suggest violence, whether to others or self-directed, might be more responsive to ﬂ  uphenazine or clozapine

(16)
A number of reports suggest violence, whether to others or self-directed, might be more responsive to ﬂ  uphenazine or clozapine 
(although the use of the latter is severely limited by its potential for marrow toxicity).
The recent proliferation of neuroleptics has been driven by a 
search for greater effectiveness together with a reduced risk of adverse effects and has been steered by the theoretical clinical attri-butes of various neuroreceptor systems. The atypical neuroleptics are reputed to bring less risk of adverse effects such as the dyskine-sias, but, as they become better known, are being linked with sedation, weight gain, and elevated prolactin level and there is growing concern about their potential to produce a metabolic syndrome.
(17) The most established of these, risperidone, has

(17) The most established of these, risperidone, has 
shown itself effective in several random controlled trials in reducing behavioural disturbance in children and adults across a number of symptoms such as aggression, social withdrawal, inattentiveness, and overactivity.
(18)
Depression, once noticed and identiﬁ  ed, is as treatable as in the

(18)
Depression, once noticed and identiﬁ  ed, is as treatable as in the 
normal population. Obsessive–compulsive symptomatology is fre-quent and responsive to the drugs augmenting serotoninergic transmission although there is increasing anxiety about potential adverse effects, particularly suicide and dependence although there is, as yet, no evidence for this in the population with intellectual disability. More frequent is a paradoxical increase in anxiety that may be a partial serotonin syndrome. The use of the selective sero-tonin reuptake inhibitors and lithium is being extended beyond the management of apparently compulsive violence and self-injury to include bouts of non-speciﬁ  c distress. Clomipramine, ﬂ  uvoxamine, 
and ﬂ  uoxetine have both shown success in random controlled trials

and ﬂ  uoxetine have both shown success in random controlled trials 
but the evidence for the effectiveness of other drugs largely consists of open label and retrospective case-series in which it can be unclear whether the underlying disorder is autism, intellectual disability, or both.
(19, 20)10.6 methods of treatment

SECTION 10  intellectual disability (mental retardation) 1876
The serotoninergic system appears to be central to a wide num-
ber of vegetative functions suggesting a potential for these drugs in appetite disorders such as the compulsive search for food and lack of satiety of Prader–Willi syndrome.
(c) b-blockers
Propranolol and nadolol limit the autonomic response to anxiety 
and the propensity to panic. They have a particular place where acute anxiety underlies aggression as, for example, in someone with autism who lashes out or ﬂ  ees in panic when feeling crowded. They 
are non-sedative but can cause lethargy and even depression. Open-label series suggest propranolol may take some weeks to take effect with a dosage range of 50–960 mg/day; characteristics that may explain the lack of random controlled trials.
(d) Stimulants
There has been a widespread re-evaluation of the place of attention deﬁ cit-hyperactivity disorder (ADHD), its prevalence, and man-

agement. Well recognized in children in the normal range of ability, 
it is now being identiﬁ  ed more frequently in adulthood, coexistent 
with autism spectrum disorder, and with intellectual disability. There is a general, unsubstantiated belief that ADHD is more intractable, the greater the degree of intellectual disability. Methylphenidate and amphetamine remain the standard treat-ments but amantadine might be more effective and less toxic.
(21)
Clonidine can be of use although sedative and short-lived and ato-moxetine is ﬁ  nding its place. When effective, stimulants can produce 
a global improvement in behaviour that includes appetite, sleep, and mood, even though anorexia, insomnia, and depression head the list of potential adverse effects.
(e) Mood stabilizers

Antiepileptic drugs are being more widely used to reduce emotional lability, particularly outbursts of rage which have an organic, pos-sibly epileptic, basis; the episodic dyscontrol syndrome. Supportive evidence is slight and occasionally the drug may make matters worse.
(22) Aggression has a large variety of causes and, after the 
exclusion of physical discomfort, the primary approach is psycho-logical. However, lithium has shown to be effective in reducing outbursts of aggression, particularly where there is irritability and explosiveness.
(16)
(f) Opioid antagonists

(16)
The hypothesis is that opioid excess might underlie both autism and its frequent associate, an indifference to pain that encourages excessive self-stimulation. Naltrexone has been used to treat both autistic disturbance and repetitive self-injury. Where autism shows any response it is to a very low dosage (5–20 mg/day), a window in a therapeutic U-curve while, if self-injury should respond, it is likely to be to a higher dosage (100–200 mg/day). Unfortunately, many of the random controlled trials have fallen between the two dosages.
(g) Antilibidinal drugs
For a few, a strong sexual drive overrides the teaching, training, and psychological therapies which, as in other areas of psychiatry, are the main approach to sexual offending. An antilibidinal agent
(23)

(23)
can supplement the other approaches, reducing the drive to a level where it is under the patient’s control. The sensitivity of this area, let alone potential adverse effects, makes it especially important that the patient, the family, and the carers are all part of any deci-sion to use medication.Conclusion

There are a large number and variety of treatments for any disorder in intellectual disability: a good indication of the complexity of dis-turbance and the inconsistency of the effectiveness of any one treatment. Therapists have an unusual responsibility not to exploit the limited ability of their patients to withhold consent as well as to try to see the world through their eyes. They have also to combine simultaneously the enthusiasm of the charismatic healer with the objectivity and scepticism of the scientist. As in any experiment, changes in treatment should be introduced singly to ensure that it is clear which manoeuvre produces which result. However, treatments complement each other and should not be used in isolation. This is the area above all in which the patient depends on teamwork and cooperation between therapists, disciplines, and agencies.
University of Birmingham. (2007) . Using medication to manage behaviour

University of Birmingham. (2007) . Using medication to manage behaviour 
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http://www.ld-medication.bham.ac.uk/.
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psychopharmacology and neuropsychiatry.  Lipincott, Williams 
& Wilkins, Philadelphia.
Handen, B.L. and Gilchrist, R. (2006). Practitioner review: 
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 3. Bohmer, C.J., Niezen de Boer, M.C., Klinkenberg Knol, E.C., 
et al. (1997). Gastro-oesophageal reﬂ  ux disease in institutionalised 
intellectually disabled individuals. The Netherlands Journal of Medicine ,
51, 134–9.
 4. Cooper, S.A., Morrison, J., Melville, C., et al. (2006). Improving the 
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33, 42–8.10.6 methods of treatment

10.7
Special needs of adolescents 
and elderly people with intellectual disability
Social health and mental health needs change throughout life, and 
this chapter highlights those particularly relevant for adolescents and elderly people. As a general rule, people with intellectual disa-bilities have the same needs as other members of the community, but they may also have additional needs for which they are entitled to extra support.
(1)
Administrative prevalence of intellectual disability in 
adulthood vs. childhood
The UK Government White Paper ‘Valuing people’ estimates that

(1)
The UK Government White Paper ‘Valuing people’ estimates that 
there are about 2 10,000 people with severe and profound intellec-tual disabilities in the UK: around 65, 000 children and young peo-ple, 1 20,000 adults of working age, and 25, 000 older people. They estimate that there are some 1.2 million people in the UK with mild or moderate intellectual disabilities. Worldwide, it is estimated that there are some 20 million people with intellectual disabilities.
(2)
Although there is now a trend in the UK towards mainstreaming 
children with special needs, and providing extra support, separate special schools for children with moderate and for severe learning difﬁ culties are still provided in many places. At school leaving age, 
many young people with mild or moderate learning difﬁ  culties 
(roughly equating to IQ > 50) will not receive special services; only

(roughly equating to IQ > 50) will not receive special services; only 
people who have severe intellectual disabilities, and those with additional disabilities, including epilepsy, autism, mental illness and/or behavioural problems will be referred on to adult specialist services. The administrative prevalence of adults with intellectual disabilities is thus much lower in adulthood as it is a measure of those in contact with services. The administrative prevalence rates should not be confused with true prevalence rates, which are far more difﬁ  cult to assess.
Transition to adulthood
Among young people in the general population, there are certain 
important life events which are usually considered necessary for a successful transition to adulthood. These include getting a job or going to college, having economic and social independence from parents, and leaving home.
(3) Although the transition to adulthood

(3) Although the transition to adulthood 
can be a difﬁ  cult and painful process for anyone, for most people 
it is also a time at which choices and opportunities open up. For people with intellectual disabilities, the transition to adulthood does not usually follow the same pattern as it does for others. For many, the transition is marked simply by an abrupt move from the protective and relatively well-deﬁ  ned children’s services to adult 
services, and by leaving school.  These imposed transitions into 
adulthood are often abrupt and traumatic for the young people and for their parents.
(4)
Overall, the criteria for ‘successful’ transition to adulthood are 
less likely to be fulﬁ  lled the greater the severity of the intellectual 
disability and other factors such as physical or mental health prob-lems, communication difﬁ  culties and/or challe nging beha viour.

disability and other factors such as physical or mental health prob-lems, communication difﬁ  culties and/or challe nging beha viour. 
Those who have mental health problems, or aggressive challenging behaviour, are particularly unlikely to receive the necessary support and services to enable them to live independent ‘adult’ lives.
(5)
In 2001, a new service, Connexions, was established to improve the management of the transition to adulthood, by providing young people from 13–19 years of age with access to advice, guidance and support.
(2)
In the UK, the majority of young people with intellectual 
dis abilities attend Day Centres.  Those who are more able may enter

(2)
dis abilities attend Day Centres.  Those who are more able may enter 
sheltered employment, workshops for disabled people or supported open employment. Relatively few people with intellectual dis-abilities are in paid employment, and although employment schemes are now being developed in many places, there are sub-stantial barriers that are faced by people with intellectual disabili-ties in getting and maintaining employment in the open job market.
(2)
In all parts of the world, the majority of young people with 
intellectual disabilities continue to live at home with one or both parents, and often have little or no social or economic independ-ence, or participation in major, or even minor, life decisions. 
Although adolescence and leaving school imply a transition to 
adulthood, in many cases young people become more dependent

1879
on their parents at this stage than they were before. For those who 
have severe or multiple disabilities, and/or challenging behaviour, there may be few practical alternatives and choices open to them.
(6)
In different countries, various approaches have been developed 
to recognize the needs of young adults. One widely adopted approach, the development of small group homes in the commu-nity, has meant that more young people with intellectual dis-abilities are able to move away from home, even some who have severe intellectual disabilities and challenging behaviour. In many countries however, the responsibility remains ﬁ  rmly with carers,

with institutional provision being the only backup when family care breaks down. An international carers’ advocacy organization, Inclusion International, researched the views of carers in 80 or more countries in both developed and developing nations, and their report makes a number of recommendations about how communities and governments can provide better support to indi-viduals and families.
(7, 8)
Health needs
There is a high prevalence of epilepsy, psychiatric disorder, hearing and visual impairments and autism among people with intellectual disabilities. Children with intellectual disabilities are the responsibility of a paediatrician, and parents can discuss and monitor their children’s needs and progress through one agency. When a child is transferred to adult services this situation changes, and there are many different agencies and individuals who become responsible for different aspects of the overall service to adolescents.

For the families concerned, the world of adult services can be 
bewildering. The situation is particularly problematic in relation to adolescents with severe intellectual disabilities, especially if there are also behaviour problems, during this transitional phase from child to adult services. Impairments in adaptive behaviour associ-ated with intellectual disability lead to problems in developing 
normal social functioning, communication, and the ability to use 
community facilities. In addition, the relationship between paren-tal and professional roles and responsibilities is often unclear. Multidisciplinary assessment is advisable, and parents should remain involved, but all too often are told that their opinion is no longer valid now their child is an adult.
(2) The Royal College of 
Psychiatrists publishes leaﬂ  ets for family carers to help them man-
age these changing professional relationships.(9)
It is often not apparent who, among the professionals, is directly

It is often not apparent who, among the professionals, is directly 
responsible for someone in the context of services, and there may be inconsistencies between Health, Education, and Social Services in terms of policies and practice. Also, health professionals, includ-ing general practitioners, may be relatively inexperienced in deal-ing with people who have intellectual disabilities.
A coherent strategy for developing comprehensive health care 
services for young people with intellectual disabilities requires collaboration between service providers, to ensure that the health care needs of all people with intellectual disabilities, including those with autism, are properly identiﬁ  ed, and that access to

mainstream primary and secondary health care is supported. One initiative developed for the white paper ‘Valuing people’ was the introduction of Health Action Plans to try to address some of these information and knowledge gaps.
(10)Mental health needs
Diagnostic overshadowing of mental illness in people with intel-lectual disabilities was common in the past, but there is now increasing awareness and assessment of psychiatric disorders, and acceptance of dual diagnosis among people with intellectual disa-bilities. A lthough mental health needs can in some cases be met by 
general mental health services, some specialized mental health provi-sion is still necessary to meet the needs of people with dual diagnosis, including those who also have challenging behaviour.
(11)
Until recently, people with intellectual disabilities were seldom

(11)
Until recently, people with intellectual disabilities were seldom 
thought to suffer from depression, but recent research shows that adolescents with intellectual disabilities report more depression and other symptoms of psychopathology than others without intellectual disabilities.
(12)
There is increasing awareness, and continuing evidence,(13,14) of 
the high prevalence of abuse of people with intellectual disabilities, of all ages, including emotional, physical, and sexual abuse, resulting in Post Traumatic Stress Disorder,
(15) severe behavioural 
disorders(16) and damaging long term effects on the family as a 
whole.(17) Challenging behaviour in people with intellectual disa-
bilities may be indicative of psychiatric disorders, such as psychosis, depression, and anxiety disorders.
A recent report concludes that people with intellectual disabili-
ties who present behavioural challenges are often marginalized, stigmatized, disempowered, and excluded from mainstream socie-ty,

(18) indicating the need for changes in policy and practice.
Sexual relationships, marriage, and parenthood
Long-term sexual relationships and parenting children are gener-ally considered to be an integral part of being an adult. In adoles-cence, emotional and sexual interest and needs develop, and it is at this stage that most young people start to have sexual relationships. However, people with intellectual disabilities are seldom encour-aged to develop sexual relationships. Parents tend to actively dis-courage it, and service managers and care staff, though they may not necessarily actively discourage it, often provide little opportu-nity, or privacy, to enable it to happen. Many people in the general population ﬁ  nd it difﬁ  cult to accept that men and women with

intellectual disabilities have ordinary sexual feelings and desires, let alone that they should be allowed to act on them.
(19) The argument 
against allowing people with intellectual disabilities to have sexual partners often involves judgments about whether someone is deemed ﬁ  t to be a parent. People with intellectual disabilities are 
discouraged from parenthood, and the experiences of childbearing and child rearing are still usually denied to women with intellectual disabilities. In Norway, 40 per cent of a study cohort of 126 chil-
dren born to parents with intellectual disabilities were found to 
have suffered from ‘failures of care’ .
(20) In England, however, 
research has demonstrated that some people with intellectual dis-abilities can become successful parents, provided they are given appropriate and effective support.
(21)
Cultural differences
People with intellectual disabilities fr om black and ethnic minori ties

(21)
People with intellectual disabilities fr om black and ethnic minori ties 
are less likely to have their needs met by service organizations as compared with the rest of the population.
(22) This is not only the 
result of difﬁ  culties in accessing services, and lack of appropriate 10.7 special needs of adolescents and elderly people with intellectual disability

SECTION 10  intellectual disability (mental retardation) 1880
information, but also because too little attention is paid to the 
different social norms, beliefs and preferences of people from different cultural backgrounds.
It is vital that service planners and providers know in what ways 
and to what extent the belief systems of the people they provide services for coincide and/or conﬂ  ict with their own. They must also 
be aware of the implications of these differences for the acceptability, expectations and outcomes of the services offered to people from 
different cultural groups.
Elderly people with intellectual disability
Life expectancy
People with intellectual disabilities have an increased risk of death compared with the general population. Whereas the majority of 
deaths (83 per cent) in the whole population in the UK occur in people aged 65 years and over, less than 50 per cent of deaths among people with intellectual disabilities are in this age group.
(23) In a

(23) In a 
study of young people in one state in the US, the mortality rate was almost three times higher than average,
(24) and in Denmark 
‘preventable’ mortality was four times higher than average.(25)
However, life span is increasing among people with intellectual dis-abilities,
(26) especially among people with Down’s Syndrome.
As a result of this increasing longevity, causes of death common 
in a normal ageing population are becoming more prevalent among people with intellectual disabilities, such as stroke, heart disease and cancer. The most common cause of death for people with intellectual disabilities is still respiratory disease, which occurs far more frequently than in the whole population, suggesting lack of effective care.
(27) This cause of death is linked to pneumonia, 
swallowing and feeding problems, and gastro-oesophageal reﬂ  ux 
disorder.
People with intellectual disabilities frequently suffer from

disorder.
People with intellectual disabilities frequently suffer from 
epilepsy, and it is suggested that the mortality rate for people with 
epilepsy and intellectual disabilities ‘may be as high as ﬁ  ve times 
that of the general population’ .(28) This high mortality rate is related 
to seizure type and frequency, rather than directly to seizures.
Cooper(29) reviews the effects of age on the physical health of 
people with intellectual disabilities, and stresses the existence of signiﬁ  cant health needs among this population. These needs arise 
not only from the normal ageing process but also from the speciﬁ  c 
social health and mental health needs of people with intellectual disabilities, including dementia. 
There are serious problems relating to access to health care,
(30)

(30)
which is further complicated by their failure, and the failure of their carers, to recognize the signs and symptoms of illness. Overall, uptake of services by elderly people with intellectual disabilities is poor. There is an increased risk for a number of medical conditions in people who have Down’s Syndrome,
(31) including sensory 
impairments, thyroid disease, leukaemia and atlanto-axial instabil-ity. The later consequences of congenital heart disease include pul-monary hypertension and congestive heart failure.
Carers may not recognize that changes in behaviour are due 
to physical or mental illness, instead attributing changes to the

to physical or mental illness, instead attributing changes to the 
learning disability itself. It is important to determine the aetiology of any learning disability, even late in life, because of the possible health implications. People with intellectual disabilities currently access health screen-
ing less than others in the general population.
(32) Pictorial health 
education materials are available to help health care professionals provide information about illness, medical procedures and treat-ment to people with limited verbal communication (for example, see www.rcpsych.ac.uk/bbw).
Signs of poor physical care among elderly people with intellec-
tual disabilities, e.g. eye infections or tooth decay, may indicate a deterioration in functioning, but may also reﬂ  ect the fact that car-
ers are not coping effectively. This emphasizes the need to ensure access to primary care.

Recent reports from the Disability Rights Commission
(33) and 
Mencap(34) identify the existing health inequalities faced by people 
with intellectual disabilities, and cite evidence suggesting the discrimination they face at every level of the health service.
Recent studies of the prevalence of mental ill-health problems 
among people with intellectual disabilities have shown that the prevalence rate of mental ill-health among adults with intellectual disabilities is higher than those recorded in the general population, with anxiety states and depression increasing with age.
(35) People

(35) People 
with intellectual disabilities are prone to the same risk factors as other people, but there are additional ones, such as living in more deprived areas, not having any daytime occupation, single marital status and epilepsy, all factors associated with mental ill-health. These factors need to be addressed if the existing inequality gap is not to be widened further.
People with Down’s syndrome have an increased risk of developing
Alzheimer’s disease in middle age. Although the neuropathological changes of Alzheimer’s dementia are widespread, development of clinical dementia is not inevitable.
(36) Dementia occurs more 
frequently among elderly people with intellectual disabilities in general than among the rest of the population, and with the increas-ing longevity of people with intellectual disabilities the number with dementia is rising.
(37)
Complexity of care needs of elderly carers and the 
people they care for at home

(37)
In households where an older person with intellectual disability is 
living with an elderly carer, there will be a complex set of individual and joint needs. Both are likely to be vulnerable at this stage in their lives, and their needs may not always be compatible.
Parents may reach a point where physical mobility and capabilities 
are declining, and in some cases dementia (in either), may compli-cate the situation. Input from services becomes essential, even if families have managed with few or no services until now. Many families will have relied on informal sources of support such as family members, friends and neighbours, but in later life these networks tend to break down, and households such as these become increasingly isolated. This isolation in the community tends to coincide with the increasing frailty of ageing carers. 
(38, 39)  Parents

(38, 39)  Parents 
of children with severe disabilities, and/or challenging behaviour, may well become isolated from kin and friends at a much earlier stage as a result of their dedicated caring role, increasing the likeli-hood of social isolation in later years.
Some elderly parents who come to light at this late stage will have 
made a decision not to accept help many years ago. This decision will have been made on the basis of information about services which were available up to 40 or 50 years ago, and elderly carers may not have received information about the range and nature

1881
of current services. There are also some parents who originally 
concealed their child’s disabilities in order to avoid institutionaliza-tion, and these parents may still be unaware of less institutionalized alternatives to care at home.
Systems of mutual caring often develop in households such as 
these, and such families may continue to be independent, in spite of serious long-term problems, and only come to the attention of the services when crisis intervention becomes necessary.
Families such as these present a double challenge to the services,

Families such as these present a double challenge to the services, 
requiring co-ordination between all relevant service providers. Co-operation between services for the elderly and those for people with intellectual disability is often inadequate, and some older people with intellectual disability fall into a limbo between them, with no one taking overall responsibility for assessing and meeting their needs. However, part of the brief of local Partnership Boards in the UK is to ensure that there is co-ordination between the services, so that individuals can obtain the range of services that they need.
(2)
Planning for the future

(2)
Ageing parents often wish to continue to look after their adult child until they can no longer cope. If a son or daughter has mild intel-lectual disability this may not cause problems for the parents, and may represent a welcome continuation of family life, especially when other children leave home. Also, as parents grow older they may become increasingly dependent on their adult child with intel-lectual disability. This may outweigh their wish to see their son or daughter settled in a new home before they themselves die, or become too frail to care for them.
Although keeping an adult with severe disabilities at home may 
cause considerable hardship, many parents are unwilling to let their child go into residential care, because they believe that only they can provide the quality of care that he or she is used to. 
Although separation and/or bereavement are likely to occur in 
the relatively near future, professionals working with families

the relatively near future, professionals working with families 
ﬁ nd that many elderly carers are reluctant to plan for their child’s 
future care, and attempts to develop care plans are often fraught with anxiety.
(40)
The experience of bereavement is often ignored by people involved with people with intellectual disabilities, although the effects of bereavement among this population are particularly severe and long-lasting, and there may be a signiﬁ  cant increase in aberrant 
behaviours, and an increase in psychopathology. The experience is often made more difﬁ  cult by their exclusion from the rituals and 
processes associated with dying and death. The onset of grief may also be delayed and thus there is a greater chance that it will not be recognized as grief, but attributed to something else or labelled as challenging behaviour.
(41)
The experience of bereavement of a parent is particularly hard

(41)
The experience of bereavement of a parent is particularly hard 
because, in addition to trying to come to terms with this loss, there are often other major life changes, such as moving into a strange home, living with unfamiliar people, and being cared for by a number of new carers.
Life changes in old age
Any major life changes in old age can have serious emotional and physical consequences. Life events which can trigger physical or mental deterioration include institutionalization, when caring 
parents die or become too frail to continue caring. This often sudden upheaval following unexpected separation or loss of a parent can be extremely traumatic.
(42) Conversely, deinstitutionali-
zation, i.e. moving into the community after a lifetime in a long-
stay institution, requires complex and sympathetic planning and monitoring.
(43)
The implications of the lack of speciﬁ  c policies for older people

(43)
The implications of the lack of speciﬁ  c policies for older people 
with intellectual disability are particularly relevant to those from black and ethnic minority groups. Their needs may not be appro-priately met by existing day services, but the alternative, i.e. living in residential homes in which staff and residents do not share the same background or language, may result in increased isolation in old age. Appropriate community services, which respond to different cultural preferences and expectations, have been devel-oped in some areas of Britain. In general, however, service providers tend to focus on the issues of age and intellectual disability, rather than the cultural background of those individuals who have different expectations and preferences in the context of age and approaching death.
(44)

(44)
St George’s, University of London www.intellectualdisability.info Down’s 
Syndrome Association UK http://www.downs-syndrome.org.uk
British Institute of Learning Disability www.bild.org.uk
The Department of Health – Learning Disabilities www.doh.gov.uk/
learningdisabilities
Down’s Syndrome Medical Interest Group www.dsmig.org.uk
The Foundation for People with Learning Disabilities www.
learningdisabilities.org.uk
International Association for the Scientiﬁ  c Study of Intellectual Disabilities 
www.iassid.org
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31. Holland, T. and Benton, M. (2004). Ageing and its consequences for 
people with Down’s Syndrome . Down’s Syndrome Association, 
London.
32. NHS Service Delivery Organization (SDO) (2004). Access to health care 
for people with learning disabilities . NHS National Institute for Health 
Research, London.
33. Disability Rights Commission (2006). Equal Treatment: closing the gap .

A formal investigation into physical health inequalities experienced by people with learning disabilities and/or mental health problems. Disability Rights Commission, London.
34. Mencap (2007). Death by Indifference. London: Mencap
35. S-A. Cooper, E. Smiley, J. Morrison, A. Williamson and L. Allan. (2007). 
Mental ill-health in adults with intellectual disabilities: prevalence and associated factors. British Journal of Psychiatry, 190, 27–35.
36. Stanton, L.R., and Coetzee,R.H. (2004). Down’s syndrome and. 
dementia. Advances in Psychiatric Treatment, 10: 50–8.
37. Cooper, S. (1997). High prevalence of dementia among people with 
learning disabilities not attributable to Down’s syndrome. Psychological 
Medicine, 27, 609–16.
38. McGrath, M. and Grant, G.(1993). The life-cycle and support networks

38. McGrath, M. and Grant, G.(1993). The life-cycle and support networks 
of families with a person with a learning difﬁ  culty. Disability, Handicap 
and Society, 8, 25–42.
39. Hubert, J.  and Hollins, S. (2000). Working with elderly carers of people 
with learning disabilities and planning for the future. Advances in 
Psychiatric Treatment, 6, 41–8.
40. Walker, C. and Walker, A. (1998). Uncertain Futures: people with 
learning difﬁ  culties and their ageing family carers . Pavilion Publishing/
Joseph Rowntree Foundation, Brighton.
41. Hollins, S., and Esterhuyzen, A. (1997). Bereavement and grief in adults 
with learning disabilities. British Journal of Psychiatry, 170, 497–501.
42. Mencap (2002). The Housing Timebomb: the housing crisis facing
people with a learning disability and their older parents . Mencap, 
London.

London.
43. Owen, K. (2004). Going Home? A study of women with severe learning 
disabilities moving out of a locked ward . University of London/Judith 
Trust, London: St George’s.
44. Mir, G., Ahmad, W., Jones, L., et al. (2001). Learning difﬁ  culties and 

10.8
Families with a member 
with intellectual disability and their needs
It is now more than 30 years since children with intellectual 
disability were among the ﬁ  rst patients to emerge from long-stay 
hospitals, where the mothers had been persuaded to part with the disabled children. The argument given was that not only would that child have the best possible chance of a happy life, but so also would the other children. Fears that there would be adverse effects on parents and on brothers and sisters prompted much of the early research.
(1)
Assessment of effects on the family
Recent sophisticated methodology has been used to explore a variety of factors, including the family as a whole as well as the parents, and what impinges on the family such as wider social, economic, and cultural inﬂ  uences.
(2,3) Positive adaptation and coping strate-
gies within families were identiﬁ  ed and are highly relevant in pro-

viding a basis for intervention. Other life events and protective or compensating inﬂ  uences are not ignored. Families with a disabled 
member are exposed to the same risk of adverse factors, such as poverty, divorce, unemployment, or mental illness as any other and, in most cases, will have the same strengths, such as humour, good friends, or staunch relatives as their neighbours. Previously, all the complaints were added together as a measurement of ‘stress’ , a concept too amorphous to be the basis of helpful intervention.
The early impact on a family of a disabled child

Diagnosis of an abnormality now frequently happens in pregnancy from screening tests or from ultrasound scans, all of which are routinely offered. T ermination of pregnancy is offered when results are positive. Although negative tests by no means guarantee nor-mality, they are often interpreted by the parents as meaning that major disability is ruled out. Hence their disappointment when a child is born with a defect is even more intense, and it often fol-lows a prolonged highly anxious period in which the baby is in special care. Initial hope is followed by temporary relief and then by the reality of gross developmental delay. Others believe they have a normal child until they become aware of the slowness of development or the onset of seizures occurs in the second half of 
the ﬁ  rst year. Parental reaction to these tragedies is often anger 
mixed with grief.
A major change in recent years has been the rapid expansion of

A major change in recent years has been the rapid expansion of 
intra-vitro fertilization. Although accurate ﬁ  gures are not available, 
it is estimated that at least 10 000 babies are born in the United Kingdom. Foetal abnormalities are more common than following normal conception as evidenced from clinical reports, but there is no data available about the effect on the parents who already have 
had much anxiety.
The mixed feelings at the time of the initial impact
The feelings that parents experience have been likened to those of grief occurring with a sudden loss. It is a useful comparison as there 
is a loss. Every expectant parent daydreams about the child and the arrival of a sick or damaged baby destroys many of those dreams. Commonly the ﬁ  rst stage is shock or a numb disbelief. The next

is a loss. Every expectant parent daydreams about the child and the arrival of a sick or damaged baby destroys many of those dreams. Commonly the ﬁ  rst stage is shock or a numb disbelief. The next 
phase is often denial, ‘This cannot be happening to me’ , followed by anger, which may be directed against the other parent, the doctor, or God. The last two phases are constructive active adaptation, which might involve learning about the condition or joining a parents association, leading on to resolution. Unfortunately, not everyone goes through all these stages and certainly not at the same rate. The mother might still be feeling as if she is shell-shocked while the father is making contact with a particular society or support group on the Internet.
The effect of diagnosis

Down syndrome is the most common disorder recognizable at birth and known to be likely associated with intellectual disability. Despite screening in early pregnancy, the condition is still common but is now often in the child of younger parents. Genetic diagnosis of unusual children is more rapid than hitherto. Parents are almost without exception relieved by a clear diagnosis, providing an explanation of why the condition has arisen as well as an estimate of future risk. Most families are also greatly helped by meeting others with similar problems. Parent support groups for each speciﬁ  c 
diagnosis are now worldwide and recruits are quickly introduced

SECTION 10  intellectual disability (mental retardation) 1884
to information via the Internet. Some diagnoses have implications 
for other members of the family, as with fragile X syndrome or tuberose sclerosis, as some relatives may have a minor form or be carriers, with a risk of further children in the family being affected. Genetic counselling is essential and may be requested very early on, in pregnancy or even before conception. T o be preventative, deci-sions have to be made fast and at times when young couples are at their most vulnerable.
(4)
The effect on the parents of a child with 
Informal support from the family or neighbours is much more 
effective than more formal, professionally led support. Frequent outpatient appointments where little happens are not cost-effective for the family; often the father loses money as he must take time off work and the cost of travel with a difﬁ  cult baby or toddler is high.

Not all can beneﬁ  t from discussion groups of parents, and other 
mothers ﬁ  nd a succession of home visits from a variety of profes-
sionals very disruptive. Families with active participation in reli-gion can strengthen family ties, especially among immigrant groups, such as Hispanic people in the United States, and Indian families, where Hinduism is central to family life and where chil-dren have speciﬁ  c roles to play, such as that of sons in funeral rites. 
A child with an abnormality makes many parents look again at their fundamental beliefs, but few make lasting changes. Other families ﬁ  nd membership of other groups (social, cultural, even 
sporting) supportive, provided that the family feels that they and 
their child are unconditionally accepted.
Family functioning with a child with intellectual 
disability at school
The ﬁ  nding concerning the greater efﬁ  cacy of informal support

The ﬁ  nding concerning the greater efﬁ  cacy of informal support 
holds true for families of children across the whole age range, from school entry to adult life. The children are enrolled into school or special preschool groups earlier than normal brothers and sisters, thus widening the informal network of friends and conﬁ  dants. 
Conversely, policies about choice of school, and the frequent necessity for children to be sent to schools at a greater distance away from home than other children, can lead to ostracism often felt more by the mother than by the child himself. An advantage of a special school is the relatively small size, allowing personal teacher–parent association and an open-door policy to parents, who are agreeably surprised to ﬁ  nd themselves enjoying the school 
years of their disabled children.
Transition to adult life

For many years, families have learnt to work in partnership with schools, and enjoyed frequent contact with teachers, face to face or thorough the progress book that goes to and from school everyday. The last few years at school are much concerned with the choice of type of further education, sometimes residential, and with encour-aging independence. The process of ﬁ  nding a suitable and accept-
able place is often described as a lottery or a battle, and is very stressful for the parents. Many have struggled through the school years, hoping that a permanent placement will be found when they come to an end. Others fear the loss of their close contact with their child, particularly if given adult rights to make choices, with which the parents do not agree. The possible outcome is one of three: independence, semi-independence, and dependence.For those who remain at home, the other children in the family

leave home as expected, leaving their disabled brother or sister in what one mother described as ‘a ghetto of the middle-aged’ . However, in many families, the provision of good further education programmes or day centres plus club or leisure activities can lead to liberation and more happiness for all members of the family. It is those with severe behaviour difﬁ  culties who are not accepted by 
further education establishments and who become increasingly frustrated and difﬁ  cult to manage at home.
Other members of the family
In many countries, the family has changed markedly in the last

In many countries, the family has changed markedly in the last 
30 years. There are many more divorces so that the ‘parents’ involved in the care of a child or young person are frequently one natural parent and one step-parent. There are also many divorced mothers living alone with the young adult after all the siblings have gone. Although some have adapted very positively, others feel very lonely, particularly if there are no members of the wider family to share the care and, often more pressing, to share the worries. Grandparents are as important in families with a member with intellectual disability as they are in ordinary families, although initially grand-parents can become severely affected by the grief, take sides in attributing blame, or offer unsought advice. One mother described her mother as an enormous help because ‘she was always behind me in every decision I took’ . When no helpful grandparent is avail-able, an older neighbour, another member of a parents group, or

a teacher at the school or day centre could provide the sort of 
informal support that has proved to be so valuable.
Ageing parents and ageing ‘children’
The physical work of looking after a still dependent and sometimes very heavy adult takes its toll on parents. With a severely physically handicapped adult ‘child’ , some help can be provided with people coming in to help with bathing, but few houses can be adapted to minimize lifting which may be needed many times during the day and night. Sooner or later the work gets too much, particularly for a sole parent. Parental frailty makes aggressive behaviour much more frightening and potentially dangerous. Where there are few opportunities for outside contact, the adult, with intellectual disability complicated by severe behaviour disorder, can become possessive and may show jealousy, sometimes making visits even from grandchildren impossible. Despite the evident difﬁ  culties, a 
study in Wisconsin,

(5) found that many parents, reaching the end 
of their lives after many years of looking after a disabled child, were ﬁ tter than others of the same age and had a much greater sense of 
having achieved something in life. Other studies of ageing people with intellectual disability have also shown the role reversal that occurs when the adult child for whom they have cared so long tenderly looks after a very old parent. Because of the increasing longevity of disabled adults as well as of older people in the general population, there are increasing numbers of very old frail parents left with a disabled offspring for whom they feel responsible and for whom they often feel anxiety about the future, commonly saying ‘I always thought he would go before us’ .
Brothers and sisters
The well-being of the family members continues to be an area of interest with an emphasis on siblings.
(3, 6) The initial decision had

1885
been made not just for the sake of the child with intellectual dis-
ability, but also in the belief that it was also in the interest of the other brothers and sisters, but it was possible that they who would pay the price. There is now a considerable body of literature con-ﬁ rming the early ﬁ  ndings that siblings are by no means invariably 
damaged. Thirty years ago, there was evidence that the older girls in the families did suffer, or were difﬁ  cult or distressed at school 
while having more than usual amounts of responsibility at home. As services improved, these ﬁ  ndings were no longer replicated 
except in those countries with few facilities and many social prob-lems. In general, the other children in the family have identiﬁ  ed 
themselves with their parents’ decisions and take some part in the caring. This ‘assistant’ parent role comes easily to older siblings, but younger siblings who grow up fast, ﬁ  rst catch up with the disabled

sibling and then overtake in development terms and in the privi-leges earned by greater maturity. Parents describe this period of catching up and gradual overtaking as one of the most difﬁ  cult in 
bringing up their children because of rivalry or jealousy. However, subsequent interviews with parents show that they are as sensitive to the needs of their ‘normal’ children as to those of the disabled child, and the balance between the siblings is readjusted. There is little evidence of long-term damage, but on the contrary, a consis-tent ﬁ  nding that the brothers and sisters are drawn to the caring 
professions, particularly medicine, nursing, or special needs teaching. The majority of families with children with intellectual disability are ordinary families with ‘one feature in common’ .
(7)

(7)
In the early months following the birth of a child recognized as hav-ing a major developmental disorder, such as Down syndrome, there was clearly much distress and disappointment, but little evidence that the mothers had a higher incidence of postpartum psychiatric disorder. Later in the childhood of the affected child, particularly in families with many other problems, depression was more common in the mothers of children with Down syndrome than in mothers of normal children. But when the mothers of children with a variety of disorders all producing intellectual deﬁ  cit were compared with 
mothers of children with Down syndrome, there were less reported health problems in the Down group. Children with brain damage and severe hyperkinesis and those with autism were rated as the most stressful. Hyperkinesis and autism both occur in Down syndrome and their families report a similar degree of stress, as recorded by the

questionnaire. For all families with a disabled child, many of the 
same factors appeared to be protective, for instance a good relation-ship with a partner and, in addition, support and affection from female relatives like the woman’s mother or sisters. There were pro-fessionally led groups, assigned social workers, and parent–teacher associations at the school, but the informal sources of support were consistently more effective than formal, with studies in the United States showing very similar results to those in the United Kingdom.
The mental heath, composition, social background, and func-
tioning of the family can increase the risk of psychopathology in the child with intellectual disability as can these risk factors for all young people.
(8) There is no evidence that severe psychiatric illness

(8) There is no evidence that severe psychiatric illness 
is more common among the families of people with intellectual disability than in anyone else. However, the combination of a severe mental illness, such as bipolar disorder coexisting in the same family with intellectual disability is overwhelming for any family, particularly if one person has the dual diagnosis.People with intellectual disability who 
become parents themselves
Although sexuality and pregnancy is a fear of many parents of 
severely intellectually disabled adolescents, their fertility appears to be very low and there are very few pregnancies in people who are totally dependent. The majority of people identiﬁ  ed as having mild

retardation during the period of education disappear from services when they leave school and so it is not possible to estimate how many women with mild or borderline retardation become mothers. However, a certain number do come before the family courts or are already known to services for other reasons. However, problems arise with planning ahead and the constant protection from danger that young babies require. There are now techniques to help teach these skills. The secret of success in such teaching is a positive attitude of enhancing skills and not one of undermining the mother. With a partner who is both stable and more able, many quite limited young women cope. As the children grow older, the problems increase as the balance between protection and encour-aging new skills becomes more difﬁ  cult. However, intellectual 
limitation in itself is not an absolute bar to parenthood. Sadly, many young women with difﬁ  culties in intellectual and emotional

limitation in itself is not an absolute bar to parenthood. Sadly, many young women with difﬁ  culties in intellectual and emotional 
immaturity are likely to ﬁ  nd partners with even more problems 
and have, for example, a high risk of being hurt by a violent man and of failing to protect children from similar abuse. It is problems such as these rather than the intellectual deﬁ  cit that make the 
courts question the safety of the children.
International perspective
The very many worldwide studies that exist show a remarkable consistency in their ﬁ  ndings. For all families of whatever ethnic

The very many worldwide studies that exist show a remarkable consistency in their ﬁ  ndings. For all families of whatever ethnic 
origin, economic status, or religious persuasion, there is grief at the birth of a child, who is in any way defective, and anxiety and sadness about a child who later is seen to fail. In some cultures, an affected boy is harder to bear than an affected girl, as boys have special roles, for instance taking part in the funeral of the parents. Obviously, a high infant mortality will mean an even higher rate in children with any sort of disability. There are a few studies that have come from countries in an early state of development. The authors of these papers are anxious not to repeat what they under-standably see as the mistakes of Europe and America. There are for example excellent community services in Asian countries based on the strengths and the beliefs of the local people,

(9) whereas others 
model their services on those in the West, and thus have similar problems but cannot reach a signiﬁ  cant proportion of the popula-
tion. Other countries in Europe are struggling to establish new services for children at the same time as they deal with the very many older people who have been poorly treated for many years. The changes are difﬁ  cult for the families of these older ones, yet 
even after many years, families have cooperated with rehabilitation and, in some cases, taken the adult ‘child’ home.
Needs and priorities
T oday in the United Kingdom the social and economic needs of these families are often unmet with a signiﬁ  cant number of 
families with a disabled child living in poverty.
(10) Most families 
will agree that the needs of the disabled member should be given priority—provided that other members of the family are in good 10.8 families with a member with intellectual disability and their needs

SECTION 10  intellectual disability (mental retardation) 1886
agreement. The needs concerning the best possible communication 
and training or appropriate treatment for behaviour problems are very much in the interests of other members of the family. Hence the needs of the others would include:
◆ education that supports the development of the child and the 
needs of the family
◆ as accurate a diagnosis as possible
◆ genetic advice to other members of the family likely to produce 
children 
◆ to be treated as informed partners by therapists and teachers
◆ available and interested primary health care
◆ a key worker to coordinate access to the different agencies and 
further ﬁ  nancial support
◆ informed specialist care within reasonable distance
◆ advice and help to ‘get through’ to the child should communica-
tion be a problem, with the chance to learn sign language, symbols, or computer aids
◆ specialist and domiciliary help with behaviour problems

◆ respite care, arranged in partnership with the family
◆ when things go wrong, support and if necessary psychiatric 
care that treats the other members of the family as whole people with many other facets and not stereotyped family members of a disabled child.

Having a child with intellectual disability is a major and usually totally unexpected blow to any family. However, most families show great resourcefulness and adapt to give their normal child as well as themselves a happy, rewarding life. Parents strongly resent being treated as potential psychiatric patients and have vigorously thrown out the concept of ‘the handicapped family’ . They do suffer under-standable grief. From the point of discharge, the encouragement of informal support is more useful than providing hospital-based services. Children with all sorts of disability go to school early and the provision of unobtrusive familiar services is helpful. Unfortunately, there is often a gap in services between children’s services and those for older adolescents and adults. The gap occurs

at the worst time for parents who of all times require a familiar knowledgeable person who can offer a service throughout the transition period. The services required by the parents are practical help, such as appropriate equipment, respite care, advice about behaviour, and the ability to ﬁ  nd emergency or specialized help 
at short notice. Parents also require some notice to be taken of their increasing age and/or inﬁ  rmity, the ﬁ  nancial difﬁ  culties arising out 
of the disability, and their anxiety that a humane plan can be made for their son or daughter when they die.
www.downs-syndrome.org.uk
www.fragilex.org.uk
 1. Tizard, J. and Grad, J.C. (1961). The mentally handicapped and their 
families . Maudsley Monograph 7. Maudsley Hospital, London.
 2. Gath, A. (1997). A review of psychiatric and family research in mental 
retardation. International Review of Research in Mental Retardation ,
20, 137–55.

2. Gath, A. (1997). A review of psychiatric and family research in mental 
 3. Hastings, R., Turnbull, A., and T onge, B. (2006). Special issue on family 
research. Journal of Intellectual Disability Research ,50, 861–988.
 4. Richards, M. (1998). Annotation: genetic research, family life 
and clinical practice. Journal of Child Psychology and Psychiatry ,
39, 291–305.
 5. Seltzer, M.M. and Krauss, M.W. (1989). Aging parents with adult 
mentally retarded children. Family risk factors and sources of support. American Journal of Mental Retardation ,94, 303–12.
 6. Blacher, J., Cameron, L.N., and Paczkowski, E. (2005). Families and 
intellectual disability. Current Opinion in Psychiatry ,18, 507–13.
 7. Byrne, E.A., Cunningham, C.C., and Sloper, P . (1988). Families and 
their children with Down’s syndrome: one feature in common . Routledge, 
London.

7. Byrne, E.A., Cunningham, C.C., and Sloper, P . (1988). Families and 
London.
 8. Emerson, E. (2003). Prevalence of psychiatric disorders in children 
 9. Miles, M. (1997). Afghan children and mental retardation: information, 
advocacy and prospects. Disability and Rehabilitation ,19, 496–500.
10. Sloper, T. and Beresford, B. (2006). Families with disabled children. 
British Medical Journal ,333, 928–9.

10.9
The planning and provision of 
psychiatric services for adults with intellectual disability
The functioning of people with intellectual disability (ID) is affected 
by many factors. As well as their ID, their ability to communicate with others, their social competency, personality, life experiences and circumstances, and their health (including mental health) also inﬂ uence their behaviour and adjustment.
This chapter focuses on the development and provision of services 
for adults with ID who have additional psychiatric and behavioural disorders. Developments have taken place in various parts of the world in recent years and a wide range of services has emerged.
History and concepts

In the mid-nineteenth century the conceptualizations of the needs of people with ID and of those with mental illness, and of how to meet these needs were separated. Intellectual disability was not then included in psychiatric training curricula and generations of psychiatrists did not see people with ID, apart from those involved with administrative functions or the prescription of psychotropic medications in institutions. The mental health needs of those with ID at this time were largely unrecognized and so ignored.
Ideologies, sociological theories, civil rights issues, and the 
normalization philosophy
(1, 2) together with families’ organizations 
inspired current care practices and directed the way ID services developed.
Policy initiatives originating in the United States during the

Policy initiatives originating in the United States during the 
1960s and 1970s produced profound and far-reaching changes offering the integration of people with ID into mainstream community life. Similar policies were adopted gradually around the world, particularly in North America, Europe, and Australasia, and in several countries the number of people with ID remaining in institutions has been drastically decreased. Deinstitutionalization of people with ID has been probably the largest social policy experiment of our time. Vivid accounts have been published recently offering enlightening narratives from individuals who were resettled in community living.
(3) Overall people with ID 
and their families have beneﬁ  ted, having a better quality of life.

and their families have beneﬁ  ted, having a better quality of life. 
Nevertheless, there are signiﬁ  cant variations in the quality of community-based services and of the experiences of people who 
use them.(4)
Psychiatric disorders and ID (dual diagnosis)
Many service planners and providers assumed that psychiatric disorders in this population would substantially diminish when community care programmes had been put in place. With the implementation, however, of the deinstitutionalization process the need for services for people with ID and psychiatric disorders emerged as a major issue.
This is because a signiﬁ  cant number of people with ID, 5 to 
12 per cent of children
(5) and 15.7 to 40.9 per cent of adults with 
ID(6) have psychiatric diso rders and despite progress in care delivery

ID(6) have psychiatric diso rders and despite progress in care delivery 
systems, require appropriate input to manage their mental health needs, sometimes over considerable time. Behavioural or psychiatric disorders can impair people’s quality of life, cause regression of adaptive and intellectual functioning, and create unnecessary escalation of family stresses.
The presence of severe behaviour or psychiatric disorders in 
people with ID is one of the main reasons for the breakdown of community placements and of rete ntion in residen tial en vironments
that are more restrictive than otherwise required. Such people are at risk of being placed in out of area facilities
(7) if local resources

(7) if local resources 
are not adequate to meet their assessment and treatment needs or ongoing support needs. These placements are often expensive and divert resources from developing local initiatives. The care provided may be inadequate and difﬁ  cult to monitor. People may lose 
contact with families, friends, and those people and structures that 
previously supported them.
It has become clear that people with ID and mental health prob-
lems need services from both the ID network and the mental health 
system. The overall position of governmental policy has been 
that people with ID should have access to generic (i.e. for anyone with or without ID) health services, but with additional specialist (speciﬁ  cally for people with ID) support when needed.
(8,9)
The argument for the provision of mental health care for people

(8,9)
The argument for the provision of mental health care for people 
with ID from generic services appears sound and is supported widely.
(10) Some argue that specialized services lead to stigmatization,

SECTION 10  intellectual disability (mental retardation) 1888
labelling, and negative professional attitudes. Others argue that 
special expertise is required for the diagnosis and treatment of psychiatric disorders in this population, because although it is theoretically possible to train staff in generic settings, the relatively small number of cases gives little opportunity for staff to gain or maintain the necessary skills.
(11)
Problems arise particularly when admissions to adult acute 
inpatient units occur, as people with ID often require longer admis-sions, and may be vulnerable without additional support on the ward. Furthermore, people with ID represent a very heterogeneous group with a varied range of highly complex mental health needs which generic staff may feel ill equipped to meet.
(10)
Menolascino(12) recommended that services be provided

(10)
Menolascino(12) recommended that services be provided 
according to need and be delivered in the context of both ID and psychiatric disorders coexisting allowing for more appropriate treatment, support, service planning, and development. The result is to create a partnership between the mental health and ID service structures to ensure responsive supports and treatments to previously underserved individuals.
Models of services for people with psychiatric 
disorders and ID
There has been a growing interest internationally as to how to 
address this issue. Davidson and O’Hara(13) offer a comprehensive 
review of service developments for this population. Long-term resolution of behavioural or psychiatric disorders in persons with ID requires community-based activi ties. Hence since the year of 
publication of the ﬁ  rst edition of the New Oxford Textbook of 
Psychiatry  new developments in most countries of the world are

Psychiatry  new developments in most countries of the world are 
community-based. The pace and form of change depends on each country’s unique historical perspective and national philosophies about care for people with ID.
(14) However, resolution of an acute 
crisis may require, in addition to community-based psychiatric or behavioural resources, inpatient acute psychiatric assessment and treatment services, specialized outreach, emergency respite, or emergency behaviour stabilization services.
The most common models of services for adults with ID and 
psychiatric disorders that have emerged in recent years in the United Kingdom can be described as: (a) generic ID community-based multidisciplinary (interdisciplinary) teams, (b) specialist community-based mental service for people with ID.
Generic ID community-based multidisciplinary 
(interdisciplinary) teams

A multidisciplinary (interdisciplinary) team offers assessment and 
specialist services to people with ID. Initially, most of these teams were involved with deinstitutionalization, carrying out tasks such as identifying appropriately adapted and staffed houses, matching clients to live together, assessing health and social needs, and so on. Most of them have input from clinical psychologists and usually some input from a psychiatrist specializing in people with ID. Some teams have developed innovative ways of working with people with challenging behaviour often with severe ID. Members specializing in functional analysis and/or behavioural treatments strengthen such teams.
One considerable problem with this model has been the lack 
of links with mainstream mental health services. Despite the psychiatric input, such services may experience difﬁ  culties in meeting

the mental health needs of people particularly those with mild ID and mental illness. The problems are extended to people with 
ID who may have additional forensic mental health problems, autistic spectrum disorders including Asperger’s syndrome and co-morbid conditions as well as those with borderline intellectual functioning.
Specialist mental health service for people with ID
Since 1982, the Community Mental Health in ID Service in South East London
(10,15) has operated using this model. It has secondary

(10,15) has operated using this model. It has secondary 
and tertiary care functions. This Service includes outpatient clinics, outreach work, inpatient assessment and treatment, and consulta-tion with community agencies. The clinical team comprises of psychiatrists, community psychiatric nurses, and administrative staff, and has a regular interface with clinical psychologists and behaviour support specialists. The clinical team also receives regular input from occupational therapists, speech therapists, and social workers. The composition and functions of the Service have evolved over a number of years. An integrated part of the Service is the provision of training to direct support care staff and others to promote and sustain the development of a competent workforce at every level, from direct care staff to managers and organizations.

There are three phases in providing clinical services: assessment, 
intervention, and follow-up.
The clinical team carries out a structured clinical assessment on 
all referrals with the additional application of standardized instru-ments, e.g. Aberrant Behaviour Checklist
(16) and CANDID.(17)
Therapeutic interventions are based on multidisciplinary work

Therapeutic interventions are based on multidisciplinary work 
and include medication and environmental manipulation, as well as psychological treatments such as anxiety management and cognitive behaviour therapy. Regular weekly clinical team meetings are held to review progress. Crisis prevention plans are developed to help families and service providers identify early signs of break-down and to take appropriate action. Training is offered to improve the capacity of families and service providers, to better understand and respond to the mental health needs of people with ID. This includes seminars, books and videos as well as modelling and role-playing exercises. Ongoing support and consultation is also provided while other specific therapeutic interventions are implemented.
Follow-up is provided for as long as it is required. Once a client

Follow-up is provided for as long as it is required. Once a client 
seems stable and the agreed upon strategy appears to be effective 
the team maintains quarterly or half yearly contacts.
If an inpatient stay is warranted for acute psychiatric crises, 
admission is into generic mental health facilities with consultative advice and support from the community-based team. Patients can also access a six-bed specialist unit at a tertiary level. The func-tion of this unit is to provide comprehensive assessment of the mental health problems when this cannot be achieved in a community setting or within generic mental health services, to make recommendations and implement therapeutic interventions and to ensure the appropriate care plans are transferred to the community setting on discharge. Care is delivered and coordinated via a person centred, Care Programme Approach (CPA),
(18,19) to 
help ensure effective links with the full range of psychiatric health and social care services.

(18,19) to 
This Service is compatible with the development of other spe cialist
services in the United Kingdom over the last few years to address speciﬁ  c needs for example of children and adolescents, older adults, 
those with forensic problems, mothers and babies, those with

1889
eating disorders, home treatment teams, assertive community 
treatment services, eating disorders teams, early intervention teams for psychosis, etc.
(20)
Outcomes
Evaluation and measuring of outcomes in mental health care for people with ID is very complex. This is because most health care service developments and reforms are politically and socially driven rather than evidence led and researchers cannot embargo change until they have deﬁ  ned systems. Accumulating evidence 
from chronological studies will still require judgement and interpretation.
(20)
Moss et al.(21) considered a variation of the Matrix Model, ﬁ  rst 
described for non-disabled people with mental health problems by Thornicroft and Tansella,
(22) for the evaluation of mental health 
services for people with ID. This consists of two dimensions, one

services for people with ID. This consists of two dimensions, one 
determined by the level within the service system (i.e. national, local, or individual), and the other by the point in the temporal sequence of service provision (i.e. inputs to the service, the process of provid-ing the service, and the resulting outcome). Bouras et al.
(15) adopted 
the Matrix Model partially (inputs and processes) to evaluate their model of service and found that over 18 years statistically signiﬁ  -
cant changes in referrals trends in ethnicity, type of residence, level of ID, the number of admissions to inpatient units and psychiatric diagnoses. In addition they also found that patients admitted to the specialist unit—in contrast to those admitted to a generic inpatient unit—showed a signiﬁ  cant decrease in psychiatric symptoms,

an increase in overall level of functioning, a reduction in severity of their mental health problems, and an improvement in behavioural function on discharge, at 6 and 12 months following discharge.
(23)
In an attempt to compare the effectiveness of assertive and stan-
dard community treatment in people with psychotic spectrum disorders and ID, with a randomized controlled study, no signiﬁ  cant 
differences were found between the two treatments.
(24)
Clinical effectiveness studies in mental health care for people 
with ID still have to overcome important methodological limitations. At present the Matrix Model
(21) seems to offer the most advanta-
geous way of evaluation, providing a framework to conceptualize the factors that inﬂ  uence service developments in the ﬁ  eld.
Residential programmes for people 
with psychiatric and ID
Successful community-living opportunities for people with ID

Successful community-living opportunities for people with ID 
require a comprehensive and collaborative service structure, includ-ing appropriate residential and vocational facilities. Ho wever, whilst 
these have been developed for many people, services to meet the needs of those with psychiatric disorders have lagged behind.
Housing for people with mental health problems must be 
compatible with all the main principles of ‘ordinary housing’ . It should be located in an acceptable community setting that offers opportunities for community integration, be designed to provide services and supports to meet the needs and desires of the person residing there, and be affordable, safe, and comfortable. This requires that staff have the necessary skills and service structures to meet client needs.
As institutions have been closed residential facilities have been

As institutions have been closed residential facilities have been 
developed in their stead. The trend across North America, Europe, and Australasia has been for larger residential homes (sometimes 
on the sites of the old institutions) to be replaced by smaller group homes for 3–8 people supported by staff. More recently, ‘supported living schemes’ have become more common, where people rent or own the property, and receive support from agencies that do not control the accommodation.
(4) The pace of change varies between 
and within countries.
The aim is to empower individuals in smaller settings, organized 
to respond to a wide range of needs, creating environments that promote physical and mental health. However, no one model will necessarily meet the needs of all individuals with mental health problems and ID. Some people may become isolated and lonely in one or two-person settings, or have difﬁ  culties that cannot be

managed in housing where additional staff or clinical support is not readily available. Some people may simply prefer to live in a supervised group living situation rather than supported living and should be given the opportunity to live in a place they prefer.
Residential services should include a full range of alternatives 
to enhance an individual’s capacity for community living. The 
individual receiving residential services should be allowed to have 
as much comfort, ownership, and autonomy as possible. Housing can offer a wide range of options, and maximize opportunities for community integration and personal independence. Specialist mental health services for people with ID should work in collabo-ration with residential providers, to provide clinical support and a safety net when difﬁ  culties arise. Delivery of services in this man-
ner represents one of the most important organizational challenges for services for people with mental health problems and ID.

Vocational programmes
Vocational services should also offer work in integrated settings in a person’s community, opportunities, and supports that are man-ageable and productive for the worker and the workplace with ade-quate salary compensation.
There have been signiﬁ  cant changes in employment and voca-

tional services for people with disabilities and several have moved from traditional workshop settings to integrated supported employment. The majority of placements have been in the service sector consistent with shifts towards entry and low-skill jobs in the national employment market. Individual placement has had the greatest positive effect on wages. Supported employment enhances the quality of life of people with ID. Although there is an accep-tance in society that people with mild levels of disabilities can be meaningfully employed, traditional views of the capabilities of 
people with severe disabilities continue to be major obstacles to their access to the most progressive contemporary, educational, 
and rehabilitation practices. People with mental health problems and ID may be under-represented in both the sheltered and supported employment workforces.
Stafﬁ  ng issues and training

The availability of specialist training varies markedly between 
countries, and not surprisingly bears a close relationship to the level of service development.
In the United Kingdom the need for specialist mental health ser-
vices for people with ID and psychiatric disorders was recognized in the early 1970s. Specialist training programmes for psychiatrists, nurses, and other health care professionals including family doctors, 10.9 the planning and provision of psychiatric services for adults with intellectual disability

SECTION 10  intellectual disability (mental retardation) 1890
community nurses, and direct care staff have been developed. 
However, whilst such training is available its uptake is dependent on the interests of individuals or of their employees. Only for some is such training mandatory, e.g. psychiatrists.
(25) Attention has 
focused in recent years on the training needs of ﬁ  rst-level care 
workers in community day and residential facilities. They often receive little or no training in the psychiatric aspects of ID with the consequence that psychiatric illness amongst their clients frequently goes unrecognized and untreated.
Beneﬁ  ts of training
Staff ﬁ  nds working with people with ID and mental health problems 
stressful. Giving them skills in this area so that they can manage, with support, people with mental health problems enables them to ﬁ nd this work more rewarding. The most basic and vital role of

stressful. Giving them skills in this area so that they can manage, with support, people with mental health problems enables them to ﬁ nd this work more rewarding. The most basic and vital role of 
support staff in this context is the awareness that a person with ID may suffer a mental illness, as we all may. They need to be aware of the range of therapeutic options that might be helpful, including environmental changes, behavioural strategies, psychotherapeutic techniques, medication, and so on. A fuller knowledge and consid-eration of this topic will help to dispel myths and prejudices, for example that medication is to be avoided at all costs, or that its use signiﬁ  es that staff has in some way failed the client. Speciﬁ  c

knowledge about some disorders will provide insights into why and how interventions must be tailored around someone’s strengths and needs, for example someone with autistic spectrum disorder may hit himself when his routine is changed. The intervention chosen may be to provide a timetable, which the staff and client follow. This may need to be in pictorial form to meet the client’s communication needs, and small and durable enough for him to carry at all times.
Training materials
Flexible training materials (e.g. The Training Package in the Mental Health of Learning Disabilities),
(26) which can be used by staff 
groups in their own settings, are now available. It is often useful to design training around particular clients. Training should be a part 
of the culture of an organization. Including managers in training activities is helpful. It allows them to share a knowledge base with 
their staff, and to set-up processes, which facilitate the continued

their staff, and to set-up processes, which facilitate the continued 
development of issues identiﬁ  ed by the training. For instance, each 
client’s mental health might be considered in his or her individual 
planning meeting. Actions agreed can then be regularly discussed 
in individual staff supervision, at staff groups, and at meetings with 
the mental health and multidisciplinary teams. Raising awareness 
on mental health issues for people with ID is also important for 
carers and families as they are a pivotal source of support.
(27)
Commissioning services

(27)
The deinstitutionalization of people with ID in the United States, United Kingdom, and other parts of the world is well-advanced. A variety of service models are provided. Comprehensive local services systems for those with additional mental health needs are emerging. The old institutions represented a complete system of care, inasmuch as they provided accommodation, health care, social care, and occupation in a single setting. Current provision, by contrast, involves a range of agencies and settings. This requires that care is integrated and organized around an individual. This is 
not an easy task for those with complex needs.
Those commissioning services need to determine what services

Those commissioning services need to determine what services 
are needed locally and decide how they should be provided, monitored, and reviewed. This chapter provides an overview of the social and policy context and some models of services for adults with psychiatric disorders and ID. Local demographics and resources will of necessity shape services. T o ensure that the commissioning of services is well-informed all planning partners should be involved. Using the Matrix Model
(21) described earlier 
the commissioners might consider:
 1  Joint commissioning. Various policies and legislation ( national 
inputs ) have proposed joint commissioning by health and 
social care services so that a joint strategy drives the joint commitment of resources ( local inputs ).
 2  Client and carer participation ( individual inputs ). This is

 2  Client and carer participation ( individual inputs ). This is 
essential to ensure that appropriate priorities are set and that services are satisfactorily delivered ( individual and local 
processes and outcomes ).
 3  Involvement of statutory and voluntary agencies ( local inputs ). 
This will enable the commissioners to make informed decisions.
 4  A baseline needs assessment of the population to be served 
(local inputs ) e.g. from census statistics, epidemiological 
research, local register data.
 5  Local and national policies ( local and national input ) to enable 
them develop a vision, e.g. community-based services, mixed economy of provision.
 6  Desired outcomes at local level  (e.g. increased use of generic 
provision, reduction in number of people placed out of area) and translate these into
 7 Service speciﬁ  cations

6  Desired outcomes at local level  (e.g. increased use of generic 
 8  Purchase services, which have the necessary skills ( local and 
possibly national inputs,  e.g. for people with very particular 
needs) to deliver processes ( local and possibly national 
processes)  that will provide these outcomes.
 9  Set in place monitoring systems, which may include individual 
and local outcomes e.g., complaints and incidents monitoring, scrutiny of statistics derived from CPA documentation (individual and local processes and outcomes ).
10 Commissioning is a cyclical process and the monitoring 
and review of services ( local inputs ) will ideally enable more 
effective future commissioning.
Components of an effective psychiatric service for people with ID 
should include:
◆ Organizing services around clients’ wishes and needs.

◆ Good interagency communication among health, social, and 
voluntary sectors.
◆ Good interagency communication between services for children 
and adults.
◆ High level of awareness of mental health issues by direct support 
staff in residential and day care services.
◆ High level of awareness of mental health issues by primary care 
staff.

1891
◆ Multidisciplinary composition including psychiatrists, mental 
health nurses, clinical psychologists, behaviour support special ists, 
therapists, and social workers.
◆ Ability to provide consultation, assessment, and treatment.
◆ Provision of community-based interventions.
◆ Access to local specialist and generic community and inpatient 
assessment, treatment, forensic, and rehabilitation facilities.
◆ Resources to meet residential, recreational, and vocational needs 
of those with enduring needs.
◆ Clear coordination of inputs by a named person.
◆ Staff training.
◆ Measuring outcomes.

There has been considerable debate as to whether specialized men-tal health service for people with ID services should be established or generic mental health service providers should serve this popu-lation. Whatever strategy is undertaken it should be based on high professional standards. Standardized diagnostic and assessment tools should be used. Appropriate, individually tailored treatments should be given in the least restrictive environments. Staff must have the necessary expertise, training, and support.
Mixed results have been obtained for the evaluation of existing 
services.
(28) No direct studies of comparative treatment effective-

services.
ness exist, and studies on single specialist services contain some methodological weaknesses. It is essential that the quality of ser-vices is monitored, to maintain and improve standards of care. Increasing fragmentation of provision makes this a complex but essential task.
Often mental health services for people with ID are provided in a 
crisis. This highlights and ampliﬁ  es the existing deﬁ  ciencies in care. 
In order to become more effective and accessible these services will have to address both individual needs and service systems complexities for children, adolescents, and adults with ID and mental health problems. Several years into the post-institutional period and the era of community care, meeting the mental health needs of people with ID remains a challenge. Though the initial 
philosophical concern about the coexistence of mental health

philosophical concern about the coexistence of mental health 
problems in people with ID has been partially eroded with the emerged evidence-based research, nevertheless the clinically effec-tive responses remain scanty. In times of hard ﬁ  scal constraints 
for mental health services in general, it is hoped that people with ID will not be further overlooked and marginalized but they will receive the required professional attention matched by adequate distribution of resources.
in intellectual and developmental disabilities . Cambridge University 
Advances in Mental Health and Learning Disabilities published by Pavilion 
Publishing. (2007). http// www.pavpub.com
Estia Centre: http://www.estiacentre.org
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 1. Wolfensberger, W. (1969). The original nature of our institutional

 1. Wolfensberger, W. (1969). The original nature of our institutional 
models. In Changing patterns in residential services for the mentally 
retarded  (eds. R. Kugel and W. Wolfensberger), p. 235. President’s 
Committee on Mental Retardation, Washington, DC.
 2. Wolfensberger, W. (1991). Reﬂ  ections on a lifetime in human services 
and mental retardation. Mental Retardation ,29, 1–16.
 3. Johnson, K. and Traustadottir, R. (2005). Deinstitutionalization and 
people with intellectual disabilities: in and out of institutions . Jessica 
Kingsley Publishers, London.
 4. Mansell, J. (2006). Deinstitutionalisation and community living: 
progress, problems and priorities. Journal of Intellectual & 
Developmental Disability ,31, 65–76.
 5. Kerker, B.D., Owens, P .L., Zigler, E., et al.  (2004). Mental health

 5. Kerker, B.D., Owens, P .L., Zigler, E., et al.  (2004). Mental health 
disorders among individuals with mental retardation: challenges to accurate prevalence estimates. Public Health Reports ,119,
409–17.
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adults with intellectual disabilities: prevalence and associated factors. The British Journal of Psychiatry ,190, 27–35.
 7. Pritchard, A. and Roy, A. (2006). Reversing the export of people with 
learning disabilities and complex health needs. British Journal of 
Learning Disabilities ,34, 88–93.
 8. Department of Health. (2001). Valuing people: a new strategy for 
learning disabilities in the 21st century . HMSO, London.
 9. US Public Health Services. (2002). Closing the gap: a national blueprint 
for improving the health of individuals with mental retardation .

9. US Public Health Services. (2002). Closing the gap: a national blueprint 
Report of the surgeon general’s conference on health disparities and 
mental retardation. US Department of Health and Human Services, 
10. Bouras, N. and Holt, G. (2004). Mental health services for adults 
with learning disabilities. The British Journal of Psychiatry ,
184, 291–2.
11. Day, K. (1999). Professional training in the psychiatry of mental 
retardation in the United Kingdom. In Psychiatric and behavioural 
disorders in developmental disabilities and mental retardation(ed. N. Bouras), pp. 439–57. Cambridge University Press, Cambridge.
12. Menolascino, F.J. (1977). Challenges in mental retardation: progressive 
ideology and services . Human Sciences Press, New Y ork.
13. Davidson, P .W. and O’Hara, J. (2007). Clinical services for people with

13. Davidson, P .W. and O’Hara, J. (2007). Clinical services for people with 
intellectual disabilities and psychiatric or severe behaviour disorders. In Psychiatric and behavioural disorders in intellectual and 
developmental disabilities  (eds. N. Bouras and G. Holt), pp. 364–87. 
14. Holt, G., Costello, H., Bouras, N., et al. (2000). BIOMED-MEROPE 
project: service provision for adults with intellectual disability: a European comparison. Journal of Intellectual Disability Research ,
44, 685–96.
15. Bouras, N., Cowley, A., Holt, G., et al.  (2003). Referral trends of people 
with intellectual disabilities and psychiatric disorders. Journal of 
Intellectual Disability Research ,47, 439–46.
16. Aman, M.G. and Singh, N.N. (1986). The aberrant behaviour checklist. 
Slosson Educational Publications, New Y ork.
17. Xenitidis, K., Slade, M., Thornicroft, G., et al.
 (2003). Camberwell

 (2003). Camberwell 
assessment of needs for adults with developmental and intellectual disabilities . Gaskell, London.
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mental health: modern standards and service models for mental health .
HSC1999/223HMSO, London.
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health services: modernizing the CPA . HMSO, London.
20. Burns, T. (2001). Generic versus specialist mental health teams. 
In Textbook of community psychiatry  (eds. G. Thornicroft and 
G. Szmukler), pp. 231–41. Oxford University Press, Oxford.10.9 the planning and provision of psychiatric services for adults with intellectual disability

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21. Moss, S., Bouras, N., and Holt, G. (2000). Mental health services for 
people with intellectual disability: a conceptual framework. Journal of 
Intellectual Disability Research ,44, 97–107.
22. Thornicroft, G. and Tansella, M. (1999). The mental health matrix: 
23. Xenitidis, K., Gratsa, A., Bouras, N., et al. (2004). Psychiatric inpatient 
care for adults with intellectual disabilities: generic or specialist units. Journal of Intellectual Disability Research ,48, 11–18.
24. Martin, G., Costello, H., Leese, M., et al. (2005). An exploratory study 
of assertive community treatment for people with intellectual disability and psychiatric disorders: conceptual, clinical, and service issues. Journal of Intellectual Disability Research ,49, 516–24.25. Costello, H., Holt, G., Cain, N., et al. (2007). Professional training for

those working with people with intellectual disabilities and mental health problems. In Psychiatric and behavioural disorders in intellectual 
and developmental disabilities  (eds. N. Bouras and G. Holt), pp. 364–87. 
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disabilities: a training resource . Pavilion Publishing, Brighton.
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families and carers of people with intellectual disabilities . Jessica Kingsley 
28. Chaplin, R. (2004). General psychiatric services for adults with 
intellectual disability and mental illness. Journal of Intellectual 
Disability Research ,48, 1–10.

11.1 General principles of law relating to 
people with mental disorder  1895
1917
 11.3.1  Associations between psychiatric 
disorder and offending   1917
 11.3.2  Offending, substance misuse, 
and mental disorder   1926
 11.3.3  Cognitive disorders, epilepsy, ADHD, 
and offending   1928
Norbert Nedopil
 11.4 Mental disorders among offenders 
1937
1945
Susan Bailey 11.8 Child molesters and other sex offenders  1960

1945
1977
1991
 11.15 The expert witness in the  Criminal Court: assessment, reports, and testimony  
2003
2009
2015
Pamela J. Taylor and Emma DunnSECTION 11
Forensic Psychiatry

11.1
This chapter provides a scheme for assisting in the analysis of 
two areas of law that provide some of the general principles that operate in relation to mentally disordered offenders. These two areas are (a) the law concerning decision-making and other action-taking to which the concept of competence is crucial, and (b) the law of responsibility in relation to liability for criminal offences and the tort of negligence. Whilst the focus of the chapter is on the law of England and Wales, it is clear that there are simi-larities in other common-law jurisdictions, and in other jurisdic-tions that have borrowed ideas from common-law jurisdiction, such as Japan, in relation to the concept of informed consent.
Decision-making and action-taking law 
and competence
Generally, the law in relation to decision-making and action-taking 
might take one of three approaches to mentally abnormal offenders.
◆ The law might adopt the same approach for mentally abnormal

◆ The law might adopt the same approach for mentally abnormal 
offenders as for anyone else.
◆ The law might adopt an approach dependent upon the compe-
tence of the individual that might be affected by the mental state of the mentally abnormal offender.
◆ The law might adopt an approach recognizing the impact of 
being a mentally abnormal offender that may be based upon the effects or mere status of the mental state.
 There is no reason to examine further the law that is not different 
for the mentally disordered.
Autonomy and Competence

There is no reason to examine further the law that is not different 
The most appropriate approach that introduces different law is by reliance upon competence or capacity. Internationally, there is increasing acceptance that, where someone is incompetent to make their own decisions, there must be a route to making such decisions on their behalf. For example, in Japan, the approach of informed consent has been adopted and whilst there is not yet a fully developed concept of competence, it is accepted that that is the next 
necessary development. Where there is signiﬁ  cant variation is in

the approach to adopt if someone is not competent. Traditionally, the approach has been to adopt guardianship whereby someone is either under guardianship or not and if so that all decisions are taken by the guardian. More recently, a more varied approach has become preferred whereby the decisions taken by others are only those that the individual cannot take and the basis for taking those decisions is the decision that the incapacitous would have made if competent and otherwise the decision that is in their best interests. It must be accepted however that this may be viewed as an approach grounded in a particular approach to law and ethics, i.e. that grounded in Western societies. Even there, there is a tradition for making decisions on a paternalistic basis, that is largely now discredited, though there are also concerns about the focus on autonomy. However, in other societies much greater emphasis is placed on the importance of the family as decision-makers or the basis of a

though there are also concerns about the focus on autonomy. However, in other societies much greater emphasis is placed on the importance of the family as decision-makers or the basis of a decision on the presumption that the individual is a part of a particular society that has a genuine and proper interests in decision to be made on their behalf. Having recognized that as an approach, this chapter will largely focus upon the Western legal systems’ basis, using England and Wales as an illustrative

jurisdiction.
Increasingly, there is recognition internationally that action 
should only be taken with regard to a person if either they are incapable of deciding or acting for themselves or if they present a harm to others (or self) and that harm is linked with a mental health problem. The extent to which different jurisdictions have a developed view of respect for the principle of autonomy and its legal application through a test for capacity or competency unsur-prisingly varies in practice. But the major issue is how decisions are to be made if someone is incapable.
International statements of principle
Acceptance of respect for the principle of autonomy can be seen through at least two international instruments. Nascently, it can be identiﬁ  ed in the provisions of the United Nations  Declaration on 
the Rights of Mentally Retarded Persons (1971) which includes the following commitments.General principles of 
law relating to people with mental disorder

SECTION 11  forensic psychiatry 1896
1  The mentally retarded person has, to the maximum degree of 
feasibility, the same rights as other human beings.
2  The mentally retarded person has a right to proper medical care 
and physical therapy and to such education, training, rehabilita-tion, and guidance as will enable him to develop his ability and maximum potential. . . .
5 The mentally retarded person has a right to a qualiﬁ  ed guardian 
when this is required to protect his personal well-being and interests.
6 The mentally retarded person has a right to protection from 
exploitation, abuse, and degrading treatment. . . .
7 Whenever mentally retarded persons are unable, because of the

7 Whenever mentally retarded persons are unable, because of the 
severity of their handicap, to exercise all their rights in a mean-ingful way or it should become necessary to restrict or deny some or all of these rights, the procedure used for that restriction or denial of rights must contain proper legal safeguards against every form of abuse. This procedure must be based on an evalu-ation of the social capability of the mentally retarded person by qualiﬁ  ed experts and must be subject to periodic review and to 
the right of appeal to higher authorities.
More recently, the Council of Europe  has agreed a set of recom-
mendations that should be implemented across Europe and are attracting signiﬁ  cant international attention, e.g. by the South 
African Law Commission. The Principles Concerning the Legal

African Law Commission. The Principles Concerning the Legal 
Protection of Incapable Adults  (Council of Europe, 1999). As Jansen 
demonstrates, the Recommendation confirms the functional approach to capacity and seeks to provide the incapable adult, where necessary, with representation, assistance, measures of protection, and other arrangements. The Recommendation opens with a state-ment that underpins the general approach adopted in this chapter:
‘I.1. The following principles apply to the protection of adults who, by reason of an impairment or insufﬁ  ciency of their personal faculties, 
are incapable of making, in an autonomous way, decisions concerning any or all of their personal or economic affairs, or understanding, expressing or acting upon such decisions, and who consequently cannot protect their interests.’

This is followed up by an important statement that captures an 
underlying theme for most jurisdictions endeavouring to provide suitable approaches.
‘II.1 In relation to the protection of incapable adults the fundamental principle, underlying all the other principles, is respect for the dignity of each person as a human being. The laws, procedures, and practices relating to the protection of incapable adults shall be based on respect for their human rights and fundamental freedoms, taking into account any qualiﬁ  cations on those rights contained in the relevant interna-
tional legal instruments.’
The principles adopted are then:
◆ securing the maximum preservation of capacity that demands 
a functional approach to capacity and so not accepting 
that someone is either capable or not capable for all decisions, 
but may be able to make some decisions and not others (II.3.1) and that no step should be taken unless it is neces-
sary (II.5.1).

◆ where steps are taken they must be proportional to the degree of capacity retained and they should be tailored to the needs and circumstances of the incapacitous person (II.6.1).◆ there just be fair and efﬁ  cient procedures for the taking of steps 
which must protect human rights and prevent possible abuses (II.7. 1 & 2). These requirements are expanded upon in Part III.
◆ the interests and welfare of the incapacitous person are the paramount consideration, thus ruling out a paternalistic basis for the taking of steps (II.8.1).
◆ the past and present wishes and feelings of the incapacitous person should be ascertained as far as possible, and should be taken into account and given due respect, and of most impor-tance are the choices made by the incapacitous person themselves (II.9. 1 & 2).

◆ there is a preference for action taken without the intervention of a judicial or administrative authority but that such powers must be limited and their exercise controlled (IV .18.1)
◆ in the health ﬁ  eld, no action should be taken if someone is 
capable of making the decision (V .22.1). The intervention may then be carried out if it is for the incapacitous person’s direct beneﬁ  t and authorization has been given by their representative 
or by an authority or person or body provided for by law (V .22.2). As not all jurisdictions are ready for this approach even in Europe, an alternative is provided so that where a person is under protective steps, the incapacitous person’s consent should be sought even though there is someone with the power to make the decision (V .23.1). Where the incapacitous person cannot provide consent, the intervention is permissible where it is for their direct beneﬁ  t and authorization has been given by their representative

or by an authority or person or body provided for by law (V .23.2).
For Jansen, the key principles are, ﬁ  rst, those in Principle 5, that 
is ‘Necessity  and Subsidiarity ’ as they ‘imply, ﬁ  rst of all, that no 
measure of protection should be established unless it is necessary, taking into account the circumstances of the particular case. Secondly, in deciding whether a measure is necessary, account should be taken of any less formal arrangements which might be provided in particular by family members, or by public authorities 
or other means. The latter is the principle known as ‘subsidiarity’ . . ..’

or other means. The latter is the principle known as ‘subsidiarity’ . . ..’ 
The second key principle is, that in Principle 3, that is ‘that of maximum preservation of capacity . . .. In particular a measure of protection should therefore not result in an automatic complete removal of legal capacity.’ The third key principle is that in Principle 6, that is ‘Proportionality: where a measure of protection is necessary it should be proportional to the degree of capacity of the person concerned and tailored to the individual circumstances of the case. The measure should restrict the legal capacity, rights and freedoms of the adult by the minimum which is consistent with achieving the purpose of the intervention.’
The international picture is completed by the Convention on

The international picture is completed by the Convention on 
the Rights of Persons with Disabilities that was signed in 2006 but is not yet in force. This is a Convention of the United Nations and has 129 States as signatories to it. The Convention is a broad Convention and covers many areas not directly relevant to this Chapter. It takes a similar approach since, its General Principles (art. 3) are (a) respect for inherent dignity, individual autonomy including the freedom to make one’s own choices, and independ-ence of persons; (b) non-discrimination; (c) full and effective participation and inclusion in society; (d) respect for difference and acceptance of persons with disabilities as part of human diversity

1897
and humanity; (e) equality of opportunity; (f) accessibility; 
(g) equality between men and women; and (h) respect for the evolving capacities of children with disabilities and respect for the right of children with disabilities to preserve their identities. In, for example, outlawing discrimination on the basis of disability (art. 4) and providing for freedom from exploitation, violence and abuse (art. 16), the Convention identiﬁ  es the balance to be drawn between 
recognising the importance of decision-making with that of pro-tecting those not capable of making their own decisions. It afﬁ  rms 
the importance of the capacity to make decisions as a key require-
ment in the law. Article 12 states that State Parties reafﬁ  rm that 
persons with disabilities have the right to recognition everywhere as persons before the law and that State parties shall recognise that persons with disabilities enjoy legal capacity on an equal basis with others in all aspects of life.

Tests of capacity and competence
Thus, it can be seen that key to respect for the principle of autono-my is to have a workable concept of capacity or competence. The functional approach requires that the test of competence be related to the particular decision to be made, at the particular time that it must be made. There is a range of abilities that competence might involve. Much of the work on competence has been under-taken in the context of health-care law and in relation to consent to treatment. Much of this work has been undertaken in the United States. Two leading thinkers, Grisso and Appelbaum, have, with colleagues, identiﬁ  ed four abilities that can be involved in 
competency:
◆ evidencing a choice
◆ understanding
◆ appreciation
◆ reasoning or rationality.
Any given jurisdiction will adopt one or more of these abilities(19)
in what it looks for in relation to competency assessments. There is

in what it looks for in relation to competency assessments. There is 
no consistency, currently, as to which one or more of the abilities must be satisﬁ  ed, except to say that almost all jurisdictions require 
understanding to some degree. This lack of consistency reﬂ  ects the 
developing international understanding of the concept of compe-tence. If we take English health-care law as an example, it can be seen that, in the early stages, understanding was the prime ability that had to be established, though the patient also had to evidence a choice. But, more recently, it seems that the courts are being attracted to an approach that may ultimately see competence only being satisﬁ  ed where all four abilities are satisﬁ  ed. Requiring rather

more of an individual to satisfy the requirement of competence may be regarded as a better means of satisfying the crucial bio-
ethical principle of self-determination or respect for the principle 
of autonomy, since if someone is not truly able to exercise self-determination, there is no respect for autonomy if, nevertheless, that person’s ‘decisions’ are legally binding. This means that rather more ‘decisions’ are open to the challenge on the basis that they are not made by someone competent to do so. A stringent approach to competence may be hard to accept. It must then be assessed (as a general matter) whether it would be better to reduce the standard and so enable more people to be assessed as competent or whether lowering the standard is illusory as being for the beneﬁ  t of people 
whose competence may be open to question. Therefore it is hardly surprising that there continues to be debate as to the abilities that

whose competence may be open to question. Therefore it is hardly surprising that there continues to be debate as to the abilities that 
any individual must possess (and the level of functioning of that ability) in order to determine whether he or she is competent to make a particular decision. Wong et al.
(19) make the point, drawing 
on the work of others, that the functional approach is not without problems. They point out that it is time consuming, legal standards vary between jurisdictions, and there is uncertainty about the threshold to be satisﬁ  ed in determining competence.
The English Mental Capacity Act 2005, sections 2 and 3 creates 
a definition of capacity consistent with those abilities. The central elements of that deﬁ  nition are to be found in sections 2(1) 
and 3(1).

and 3(1).
2(1) For the purposes of this Act, a person lacks capacity in relation to a matter if at the material time he is unable to make a decision for himself in relation to the matter because of an impairment of, or a disturbance in the functioning of, the mind or brain.
3(1) For the purposes of section 2, a person is unable to make a deci-
sion for himself if he is unable –
(a) to understand the information relevant to the decision,(b) to retain that information,(c) to use or weight that information as part of the process of 
making the decision, or
(d) to communicate his decision (whether by talking, using sign 
language or any other means).
Three approaches

What is key is that the approach is a functional one that is it is related to the abilities of the individual at the time a decision is required and is not dependent upon either status or outcome of the decision, though these clearly have formed part of either deﬁ  ni-
tions or approach to capacity in the past and are relevant factors in identifying the possibility that someone may not be capable of decision-making and in exercising judgment about that capacity. T o state that competence if to be interpreted functionally.
(19) means 
that the status of the decision-maker is not determinative of the question of her or his competence. A status approach  makes 
assumptions about an individual’s decision-making competence on the basis of a particular characteristic, and there is no empirical evidence to support the validity of such an approach.

(19,21) The 
mental state of the decision-maker may be the reason why compe-tence is put into question, but mental state in itself is rarely, if ever, sufﬁ cient to determine the matter. Mental state may have relevance 
to decision-making in that certain states will impact on the ability to understand and process information. Furthermore, the outcome of a decision is also not in itself sufﬁ  cient to determine the matter.

The fact that any given decision is not reasonable does not mean that the decision-maker is not competent to have made that deci-sion. For example, the simple fact that a patient disagrees with the doctor does not mean that the decision is that of an incompetent decision-maker, though lack of congruence with the proposals of a doctor may cause questions to be asked about decision-making 
competence. The outcome approach  has been rejected in a number 
of jurisdictions.
(19) It is internationally recognized that anyone can 
make what might be termed objectively silly decisions without necessarily giving rise to doubts about competence. However, the regularity with which silly decisions are made may raise doubts about competence as also will the inter-relation between mental state and quality of decisions. In the United Kingdom, these points are further reﬂ  ected in the fact that there is a legal presumption 11.1 general principles of law relating to people with mental disorder

SECTION 11  forensic psychiatry 1898
that a person is competent to make her or his own decision once 
adult state is reached.
The functional approach  requires that the test of competence 
be related to the particular decision to be made, at the particular time that it must be made.
(19) There is a range of abilities that 
competence might involve. Much of the work on competence has been undertaken in the context of health-care law and in relation to consent to treatment. Much of this work has been undertaken in the United States. Two leading thinkers, Grisso and Appelbaum,
(20)
have, with colleagues, identiﬁ  ed four abilities that can
The functional approach to decision-making is not limited, in its

(20)
The functional approach to decision-making is not limited, in its 
application, to health-care decisions, even though that is where most of the debate has taken place. In principle, it may be applied to any type of decision. For example, the making of wills and the entering into of contracts are obvious examples where a functional approach applies, but it does not follow that the same abilities will be required for these decisions as for treatment decisions. Under the law prior to the Mental Capacity Act 2005, this is dem-onstrated by an old case which was, nevertheless, the leading case in relation to the making of wills. Banks  v. Goodfellow , requires that 
a person:

a person:
ought to be capable of making his will with an understanding of the nature of the business in which he is engaged, a recollection of the property he means to dispose of, of the persons who are the objects of his bounty, and the manner in which it is to be distributed between them.
This test demanded not just understanding, but also the appre-
ciation and the reasoning ability noted above. Whilst the level at which the will writer must operate is not that of a lawyer, never-theless he or she must be aware of the context in which the will is being made and must think through the competing potential demands on his or her estate. Of course, will writers can make silly dispositions, even going so far as to exclude ﬁ  nancially dependent

relatives. However, it must be recalled that an outcome that is questionable or unreasonable is not the same as the will or decision being made on the basis of an unacceptable reasoning process. An eccentric person might well, for example, not wish to leave any-thing to his or her relatives. Thus, in any jurisdiction, care must be taken to consider a particular test in deciding which of the four abilities are to be identiﬁ  ed, and the answer to that question may 
demand very careful analysis.
Persons not competent to make decisions or 
take action
If a person is not competent to make a decision for themselves,

If a person is not competent to make a decision for themselves, 
there is more variability as to the approach to be taken. Some of this difference is related to the commitment to do the best for a vulnerable person and leads to a desire to act paternalistically, so making the decision that objectively is in the best interests of the individual A more frequent approach is to make the decision that that individual would have made for themselves. This is most recently reﬂ  ected in the English Mental Capacity Act.
If a person is not competent to make a decision or to take certain 
action, the law increasingly provides mechanisms whereby these decisions can be made. In England and Wales, until the abolition of the sign manual by the Mental Health Act 1959, the Crown had the 
power and the process to make decisions in the best interests of

power and the process to make decisions in the best interests of 
a person not competent to decide or to take action. This power is the basis of many substitute decision-making procedures in com-
mon-law jurisdictions (including the United States). The speciﬁ  c 
adaptation is jurisdictionally speciﬁ  c. In some jurisdictions, it has 
been used to follow from generic decisions as to competence and to create overarching substitute decision-making procedures (e.g. those jurisdictions that adopt a full guardianship of the person 
approach). In England and Wales, the ﬁ  rst approach, after the 
abolition of the sign manual procedure, was to allow for people to be received into guardianship (a process that was not, interestingly, dependent upon a ﬁ  nding of incompetence), but this proved not

to be an acceptable procedure. Current English guardianship is very much only a community mental health power that does not enable anyone else to make decisions on behalf of the person received into guardianship.
(33)
In England, the courts had to invent a procedure for making

(33)
In England, the courts had to invent a procedure for making 
decisions on behalf of someone who was not competent. The House of Lords, the senior English court, provided a mechanism in rela-tion to treatment decisions whereby, if a person was found to be incompetent, treatment could lawfully be provided if it was necessary, that is if it was for the life, health, or welfare of the patient and was in her or his best interests. Despite substantial improve-ments that made the approach identify what was the one, best approach that took into account the full range of interests (see below), this judicial approach has been replaced by a statutory format. The approach introduced by the Mental Capacity Act 2005, does not take a full guardianship or guardianship of the person approach and is not necessarily triggered by a judicial or adminis-trative authority. Rather, a person may act on behalf of an incapaci-tous adult (as deﬁ  ned by sections 2 and 3, see above) provided she

or he acts in that person’s best interests (as deﬁ  ned by section 4, see 
below), but such actions are subject to signiﬁ  cant procedural pro-

tections, since some areas must be referred to other procedures (e.g. in relation to research, where sections 30–34 allow intrusive, non-therapeutic treatment consistently with the European Convention on Biomedicine), some decisions cannot be made as they are too personal (so such matters as consenting to marry or to entering a civil partnership and consenting to sex do not fall within the Act, see section 27), some decisions necessitate, where carer’s views are not available, the views of an independent mental capacity advocate to be taken into account (sections 35–41), some decisions may be made by a court or by a court appointed person where the court determines that is appropriate (through the new Court of Protection, with preference given to decisions made by the court rather than the appointment of a deputy), and all decisions are challengeable in court. This latter element is vital. Whilst this approach is clearly consistent with the provisions of Recommendation 99(4), it is

the appointment of a deputy), and all decisions are challengeable in court. This latter element is vital. Whilst this approach is clearly consistent with the provisions of Recommendation 99(4), it is chal-lengeability which lies at the heart of its compliance with human rights obligations. What the Act does not do is require an initial judicial or administrative decision. It is not triggered by having to go to court or through some other governmental or quasi-govern-mental body. This will no doubt be challenging to many whose commitment to due process and procedural justice would rely upon judicial instigation of a procedure. However, this is not the only necessary approach, as is evidence in Recommendation 99(4). What is provided instead is a straightforward ability to challenge decisions by taking a matter about competence or about decisions made on behalf of someone who is or may be incompetent to the Court of

Protection. Some people can launch a case as of right, some need the 
permission of the Court (section 50). This is clearly sufﬁ  cient to meet

1899
the demands of, for example, Article 6 of the European Convention 
on Human Rights, provided it operates in practice. If it fails to take cases that should get to the Court, then that might be a base of chal-lenging the provision. The advantage of this approach, which are con-sistent with that of Recommendation 99(4), is that it more closely reﬂ ects the process applicable in relation to someone who is capable, 
it places emphasis on the fact that most decisions are taken on behalf of an incapable person by carers and those decisions are proper and appropriate and it provides a system that can work (that is the work-load should be manageable and not be prohibitively expensive).
The focus for making decisions on behalf of another in England 
and Wales as in most jurisdictions, is individualized, function speciﬁ  c and based on the best interests of the individual. This best
interests approach  is, realistically, the only one available to the courts

interests approach  is, realistically, the only one available to the courts 
where there is no evidence of that person’s preferences. Substituted 
judgement is, however, an appropriate approach where there is suf-ﬁ cient evidence of the decision that the person now incompetent 
would have made.
(30) So, for example, decisions made in advance, 
advance health-care statements, are legally valid(22) (see also 
Kennedy and Grubb,(30) referring to such an approach in Florida,

Ontario, Manitoba, and Victoria). Indeed, the old thinking that substituted judgement was an alternative to best interests should be re-thought so that what an individual wants is what is in her best interests, but if that is not known, nest interests is the only available approach. Where the person is not competent, the best interests approach, in England, was achieved by deciding whether what the doctor proposes in the given case is a treatment regime of which a responsible medical opinion would approve. This approach to ‘best interests’ was rightly severely criticized for it failed to address the issue by concentrating upon the interests of incompetent persons but professionalized it through one (medical) profession when it is possible to take a broader view of the issues in question when deciding upon what treatment to agree upon. Some of these criti-cisms were ameliorated by judicial developments (see, e.g. Re S (Adult Patient: Sterilization)  and Re A (Male Sterilization) )

that ensured two key changes. First, it was decided that, where there were options of a number of possible, acceptable approaches, only one of those options could be in the best interests of the individual. Secondly, in deciding what was in someone’s best interests that should not be limited to scientiﬁ  c or medical matters, but should 
take in the whole range of social, welfare, and emotional factors. Despite such substantial judicial development, new law is in place through the Mental Capacity Act 2005. Section 4 provides a deﬁ  ni-
tion of best interests.
4(1) In determining for the purposes of this Act what is in a person’s best interests, the person making the determination must not make it merely on the basis of –
(a) the person’s age or appearance, or(b) a co ndition of his, or an aspect of his behaviour, which 
might lead others to make unjustiﬁ  ed assumptions about 
what might be in his best interests.
(2) The person making the determination must consider all the

(2) The person making the determination must consider all the 
relevant circumstances and, in particular, take the following steps.
(3) He must consider –
(a) whether it is likely that the person will at some time have 
capacity in relation to the matter in question, and
(b) if it appears likely that he will, when that is likely to be.
(4) He must, so far as reasonably practicable, permit, and encourage 
the person to participate, or to improve his ability to participate, as fully as possible in any act done for him and any decision 
affecting him.
(5) Where the determination relates to life-sustaining treatment 
he must not, in considering whether the treatment is in the best interests of the person concerned, be motivated by a desire to bring about his death.
(6) He must consider, so far as is reasonably ascertainable –
(a) the person’s past and present wishes and feelings (and, in

(a) the person’s past and present wishes and feelings (and, in 
particular, any relevant written statement made by him when he had capacity),
(b) the beliefs and values that would be likely to inﬂ  uence his 
decision if he had capacity, and
(c) the other factors that he would be likely to consider if he 
were able to do so.
(7) he must take into account, if it is practicable and appropriate to 
consult them, the views of –
(a) anyone named by the person as someone to be consulted on 
the matter in question or on matters of that kind,
(b) anyone engaged in caring for the person or interested in his 
welfare,
(c) any donee of a lasting power of attorney granted by the 
person, and
(d) any deputy appointed for the person by the court,
as to what would be in the person’s best interests and, in particu-
lar, as to the matters mentioned in subsection (6).
The law relying on status

Whilst it has so far been asserted that approaches not facilitating decision-making by a competent person are the norm and that capacity should not be questioned on the basis of status, it is the case that status may play a role. Indeed, for example, in England and Wales status has, in the past, been the basis for effectively deter-mining whether someone is capable, but increasingly these are being removed, as is the case across the globe. It is also a move demanded by international instruments, such as the Council of Europe Recommendation.
In England and Wales, it used to be the case that children under 
16 were not able to consent, but the House of Lords changed this in 1985 when, in Gillick  v Wisbech AHA  it was recognized that,

16 were not able to consent, but the House of Lords changed this in 1985 when, in Gillick  v Wisbech AHA  it was recognized that, 
at least for some treatments, a person under the age of 16 could be capable of deciding upon treatment provided they had sufﬁ  cient 
maturity to do so. The removal of the automatic barrier was an 
important step.
Further, the Sexual Offences Act was another example of law in

Further, the Sexual Offences Act was another example of law in 
a private area that was dependent upon status. For most people, it always has been a matter that is dependent upon their own consent. So, for example, it is rape for a man to have anal or vaginal sexual intercourse with a woman or a man who does not consent. The critical question is whether the victim is competent to make the decision. For example, does she or he understand what sexual inter-course is so that her or his apparent assent is indeed consent? However, under the 1956 Act this was not the case in all instances. First, there was an age of consent. Below the relevant age, the consent of the victim was irrelevant, however competent she or he may be. Second, a person who was a ‘defective’ in the terms of the Sexual Offences Act 1956 or had a ‘severe mental handicap’ could not consent. These terms were deﬁ  ned in the same way and referred

to a person who had a state of arrested or incomplete development of mind that is associated with severe impairment of intelligence 11.1 general principles of law relating to people with mental disorder

SECTION 11  forensic psychiatry 1900
and social functioning. If a person fell into this category, she or he 
could not, in law, consent to sexual intercourse or other sexual activity, however competent he or she might have been. This had real impact on some people with mental retardation (intellectual disability) and their carers. Interestingly, if a man married a woman with a severe intellectual disability (who was, therefore, a ‘defec-
tive’), he did not commit the offence contrary to Section 7 of the 
Sexual Offences Act 1956 (whereby it was an offence for a man to have unlawful sexual intercourse with a woman who was a defec-tive). Marriage was and is not dependent upon status, but is dependent upon an assessment of the competence of the particular individuals at the time of the marriage ceremony, and so falls into the second category of laws.
(33) The law meant that a person could

(33) The law meant that a person could 
not prevent an indecent assault in any circumstances by consent. This could have unfortunate consequences for sex education for some people with severe mental retardation. It may be that no other form of sex education is possible than hands-on education to provide skills to enable appropriate behaviour by the person in question. Whatever the level of necessity, the individual could not consent in law. The only possible defence was to argue thatthe activity, contrary to appearances, was not indecent because of the purpose for which it was being undertaken as evidenced by the context, that is a carefully tailored and developed personal relation-ships programme. The difﬁ  culty here was that, when perceived 
from this stance, the law fails to allow sexual expression without good individual reason. Therefore it could be contrary to Article 8 
(privacy) or Article 12 (founding a family) of the European

(privacy) or Article 12 (founding a family) of the European 
Convention on Human Rights. The law presumably assumed that sexual experiences would, by deﬁ  nition, exploit or abuse such peo-
ple. Law to prevent exploitation and abuse is very important, but it must not improperly limit a person’s human rights. Subsequently, there has been an attempt to redress the balance somewhat and provide for a set of laws that is more acceptable. The Sexual Offences Act 2003 creates three types of offences that have an impact where 
the victim is a person with a mental disorder. The ﬁ  rst consists of

the victim is a person with a mental disorder. The ﬁ  rst consists of 
offences involving sexual activity with a person with a mental dis-order and apply where that person cannot consent. The second consists of offences where the person’s agreement is achieved through an inducement, threat or deception. The third comprises offences where the defendant is in some form of care relationship with the victim and these offences are committed regardless of consent and clearly deal with a signiﬁ  cant form of exploitation and 
abuse. It is worth focusing, brieﬂ  y, on an exemplar from the ﬁ  rst

abuse. It is worth focusing, brieﬂ  y, on an exemplar from the ﬁ  rst 
type of offences. Section 30 of the 2003 Act makes it an offence for someone to engage in sexual activity with a person with a mental disorder impeding choice. As the offence relies upon touching, it involves sexual intercourse and other sexual activity short of intercourse but that involves touching. What it does not include is activity that would not involve touching, but would have been regarded as an assault under the old law. That touching must be sexual. It remains to be clariﬁ  ed whether sex education of a direct 
manner described above would be caught, but there must at least be an argument that it would not, provided that there is a non-sexual purpose, established by the education programme within which it falls and that a multi-disciplinary group identiﬁ  es

the need for the touching and the means of doing it. The offence applies potentially to anyone with a mental disorder, and is not so status driven as was the old law reliant upon being a defective or a person with a severe mental handicap. There is, though, still the status requirement of a mental disorder, which might be justiﬁ  ed 
upon the basis of necessity and proportionality, as there must be an inability to refuse on the basis of that mental disorder, so the offence does not apply simply because of the presence of the disor-der. This requirement is the equivalent of a capacity requirement tied to the speciﬁ  c requirements of the matter in hand. Finally, the

defendant must know or could reasonably have known of the oth-er’s mental disorder and that he or she is thereby unable to refuse. These offences are likely to produce a much better balance of the need to protect the rights of vulnerable persons to understand and exercise their sexuality with their right to be protected by the law from sexual abuse and exploitation.
The law of responsibility
Criminal liability

Mental disorder is relevant to criminal liability in a variety of differ-ent ways, and this is true, at least, in all common-law jurisdictions. First, the presence of a mental disorder may be a reason to convince the decider of the fact that, contrary to external appearances, the defendant did not have the mental element for the crime with which he or she has been charged. Lack of the mental element is, of course, a complete defence. Whilst there is not a mental element requirement for all crimes (since there are some crimes for which conviction is based on strict liability), most serious crimes require a mental element that takes the form of intention, recklessness, knowledge, or belief and demand a consideration of what was the individual’s purpose, awareness, foresight, or realization at the time that the crime was committed.
Second, the presence of a mental disorder may give rise to

Second, the presence of a mental disorder may give rise to 
a defence. This will arise either by it being raised by the defence

a defence. This will arise either by it being raised by the defence 
(even if the defence does not have the formal burden to prove it, but will have the burden of raising the matter for consideration) or by the prosecution challenging a point made by the defence (so, for example, if the defence raises mental disorder as an explanation for lack of criminal intent, the prosecution may respond by arguing that the defence has, in fact, raised one of the defences concerned with mental disorder). The most obvious defence is that of insanity. Whilst this takes various forms in many jurisdictions, there is usu-ally a relationship in common-law jurisdictions with the English defence that was established by judicial answers to questions posed in McNaghten’s case in 1843. This defence demands that the following matters be established by the defence (this is one of those rare instances in which the burden of proof lies, on a balance of probabilities, on the defence).

The defendant must have a disease of the mind. There are at least 
two possible ways of approaching this concept. First, it may be regarded as a simple concept in that it is present if the defendant has a condition (loosely termed) that has an internal cause, whereas there is no disease of the mind if there is an external cause. This simplistic distinction means that a person who has a brain tumour has a disease of the mind as does a person who has arteriosclerosis, schizophrenia (or other mental illness), epilepsy diabetes (provided the defendant had not taken her or his insulin and caused the offence in a hypoglycaemic state, or is a sleepwalker). The person with diabetes who causes the offence after taking insulin (an exter-nal agent) but falls into a hypoglycaemic state does not have a disease of the mind because the cause (insulin) is external and not internal. Immediately it can be seen that there is no congruence

1901
between the legal construct of disease of the mind and any medical 
approach. Furthermore, this deﬁ  nition of disease of the mind pro-
duces outcomes that are clearly unacceptable (no one would argue that many of the conditions identiﬁ  ed above are identiﬁ  able with 
mental disorders). An alternative deﬁ  nition, which may reduce 
some of the impact of the concept is to follow Lord Denning: 
‘it seems to me that any mental disorder which has manifested itself 
in violence and is prone to recur is a disease of the mind. At any rate it is the sort of disease for which a person should be detained in hospital rather than be given an unqualiﬁ  ed acquittal’ .
One difficult area of applying the external/internal causes

One difficult area of applying the external/internal causes 
distinction is in relation to ‘whether a ‘dissociative state’ resulting from a ‘psychological blow’ amounts to insane automatism’ . This was recognized by the Supreme Court of Canada so that the psy-chological blow can be recognized as an external cause giving rise not to insanity but to automatism as a defence.
The disease of the mind must cause a defect of reason. Defect of 
reason means that ‘the powers of reasoning must be impaired and that a mere failure to use powers of reasoning which one has is not within the [McNaghten] Rules’ .
(47)
The consequences of actions A and B must be that the defendant 
either does not know what he is doing or does not know that what he is doing is legally wrong. The latter is contentious, because the Rules simply state that the defendant must know that what he was doing was wrong. In R v. Windle  it was the Court of Appeal that

established that the requirement was that the matter is concerned with legal wrong. The High Court of Australia has refused to follow this approach. In Stapleton  v. R, ‘their view was that if D believed 
his act to be right according to the ordinary standard of reasonable men he was entitled to be acquitted even if he knew it to be legally wrong’ .
(45)
The outcome of a ﬁ  nding of insanity is that the defendant is 
found not guilty by reason of insanity and, since the amendments introduced by the Criminal Procedure (Insanity and Fitness to Plead) Act 1991, the disposal of the defendant is not limited to being sent to a mental hospital under the equivalent of a restriction 
direction, but extends to less draconian forms of disposal, includ-
ing discharge.
Third, there are limited or partial defences. In English law there 
is a defence of diminished responsibility that is a defence only to 
murder and produces, if successfully raised by the defendant,

murder and produces, if successfully raised by the defendant, 
a conviction for manslaughter. There are similar defences, often of more general application in most, if not all, common-law countries. The defence of diminished responsibility was created by the Homicide Act 1957, Section 2, which provides:
Where a person kills or is a party to the killing of another, he shall not be convicted of murder if he was suffering from such abnormality of mind (whether arising from a condition of arrested or retarded development of mind or any inherent causes or induced by disease or injury) as substantially impaired his mental responsibility for his acts and omissions in doing or being a party to the killing.
The question of impairment of responsibility is one for the

The question of impairment of responsibility is one for the 
decider of fact to make. Interestingly, expert evidence usually con-tains an assessment of the degree of impairment, though this would appear not to be a matter upon which the expert has the relevant training or expertise. Were the expert witness not to proffer a view on the matter, the practical reality is that the court would ﬁ  nd it 
very difﬁ  cult to know how to react to a claimed defence. The 
original rationale for this partial defence was to avoid the rigour of capital punishment. Its current rationale is wide ranging. Amongst 
other reasons why this defence is important is that it allows the 
defendant to argue that he or she was incapable of resisting an impulse produced by mental disorder, an argument that is not per-missible in the insanity defence as is made clear by the McNaghten Rules themselves.
Fourth, there are other defences which are or may be related to

Fourth, there are other defences which are or may be related to 
mental disorder. One obvious defence is that of intoxication. If a person is intoxicated by drink or drugs such that he or she does not have the criminal intent for an offence, he or she is not guilty of that offence provided the offence is one of speciﬁ  c intent (such as 
murder), whereas he or she will be guilty if the crime is one of basic intent (such as manslaughter). Although a range of theories have been propounded to establish when a crime is one of speciﬁ  c or 
basic intent, the only approach that actually works is to take previ ous 
decisions as precedents for future approaches, and so develop a list of crimes of speciﬁ  c and of basic intent.
Tortious liability
Liability in tort encompasses a wide variety of non-contractual

Liability in tort encompasses a wide variety of non-contractual 
civil wrongs, including such diverse matters as negligence, nuisance, defamation, and trespass to land. It is worth noting that trespass to the person (assault and battery) is a civil wrong as well as a criminal offence and concurrent liability will lie. A battery occurs when there is a non-consensual touching, which includes the administration of medical treatment and care so that regardless of any benevolent motivation, if this is given without a valid con-sent an action will lie. However, this section concentrates on the law of negligence which is the main area where liability problems might occur. Again, the authors must emphasize that we concen-trate mainly upon English law, but within the area of tort the law in other English-speaking jurisdictions is very similar e.g. in the USA,

Australia, New Zealand, and Canada, and even in codiﬁ  ed jurisdic-
tions, such as France, Spain and Germany, there are similarities of approach.
In this section we look ﬁ  rst at the general principles of the law of 
negligence. Second, any special considerations when examining the liability of the mentally ill defendant in an action in negligence are discussed. Third, the liability of third parties for the acts of the mentally ill are examined, and ﬁ  nally, the liability of third parties 
towards mentally ill patients, particularly in the context of statutory duties, and the difﬁ  cult and controversial issue of the liability 
towards patients who harm or threaten harm to themselves are discussed.
(a) Negligence
The law of negligence is heavily circumscribed by a conceptual framework which is designed to restrict the ambit of claims. Much of this need not concern us here, sufﬁ  ce to say that the most 
relevant parts of it relate to the difference between certain types of

relevant parts of it relate to the difference between certain types of 
loss and the way in which the courts regard these differences, and the role of public policy in some of the principal judgments.
The basic requirements of the tort of negligence have a certain 
simplicity; it is in the application of these requirements that complexity and confusion result. The claimant must show (a) that the defendant owed him or her a duty of care; (b) that the defend-ant breached that duty by failing to meet the requisite standard of care, and (c) that the breach of duty caused the resulting damage. It is important to note the latter. Negligence is not actionable per se ;11.1 general principles of law relating to people with mental disorder

SECTION 11  forensic psychiatry 1902
there must be some tangible damage caused by the breach. There is 
insufﬁ  cient space here to consider duty of care in all its contexts, 
but it is important to note the test put forward in Caparo Industries 
PLC v. Dickman . In that case it was said that in order for a duty of 
care to arise, the damage suffered must be foreseeable; there must be sufﬁ  cient proximity between the claimant and the defendant; 
and it must be ‘just and reasonable’ to impose a duty of care. The ﬁ rst two aspects are well illustrated by examining the difference 
between physical injury and other forms of damage; the third is an important consideration in the context of statutory duties. As far as the standard of care is concerned, the standard is objective and based upon reasonableness. Causation must always be proved as there will be no liability for falling below the requisite standard of care if a causal link to the damage cannot be proved. The stand-

ard of proof throughout is that of the balance of probabilities.
(b) Liability for clinical negligence
Duty of care is not usually an issue in the doctor/patient relation-
ship. It should be noted that the standard of care relating to profes-sionals such as doctors is set by the ‘accepted practices’ test, well known as the ‘Bolam test’ as framed in the case of Bolam  v. Friern 
Hospital Management Committee , where diagnosis and treatment 
will not normally be negligent if supported by a responsible body of medical opinion. The only exception to this is if the doctor’s actions do not withstand logical analysis; in those circumstances the fact that the practice is ‘accepted’ will not be sufﬁ  cient to avoid 
a ﬁ nding of negligence. The test is slightly different if the allegation

a ﬁ nding of negligence. The test is slightly different if the allegation 
of negligence relates to the provision of inadequate information about risks, side effects and alternative treatments. In such cases it seems that the courts are moving towards a more stringent stand-ard of informed consent. Proving that the damage was caused by 
the breach can raise many problems in medical negligence claims, 
largely for two reasons. First, in almost all cases the patient will be suffering from some medical condition at the outset, and it might be arguable that the resulting condition would have materialized anyway. Second, if the resulting condition is the realization of some form of risk (e.g. side-effects of medication), even if the patient was not warned of the risk it is open to the defendant to argue that regardless of warnings, the patient would have gone ahead and consented to the taking of the medication in any event.
(c) Liability for different types of damage—psychiatric injury

The law distinguishes between different types of damage. This appears to stem from judicial fear that certain losses might result in an unacceptably large number of potential claimants i.e. the fear of opening the ‘ﬂ  oodgates’ . Thus, what is known as ‘pure economic 
loss’ , that is ﬁ  nancial loss, which is not consequential upon physical 
damage, will only be recoverable in certain circumstances. For similar reasons the law makes another signiﬁ  cant distinction: the 
difference between physical damage and psychiatric damage.
There are a number of reasons for the disparity between the 
treatment of the two types of injury. The ﬁ  rst stems from the mis-
understanding in earlier cases of the nature of psychiatric injury. In the authors’ view, it is no coincidence that some of the early cases involved pregnant women who had miscarried or given birth to damaged children (e.g. Dulieu  v. White & Sons ). In these cases the

courts could see a tangible manifestation of the ‘shock’ suffered by the claimants. Psychiatry was in its infancy, and the myriad of sub-
tle manifestations of mental disorder was unknown. A further illustration of this is the phenomenon of ‘railway spine’ . In 1875, J.E. Erichsen, Professor of Surgery at University College Hospital, 
London, published a number of ﬁ  ndings as a result of studying 
spinal injury cases following railway accidents, where there was no obvious physical cause of the symptoms manifested. His con-clusion was that trauma caused ‘concussion of the spine’ . Later medical opinion such as that of surgeon Herbert Page denied that the spine as such was affected by the trauma, but that the resulting condition was ‘nervous shock’ . It is therefore understandable that courts may have taken a somewhat crude approach to shock-induced injury, which crudity is still reﬂ  ected in the law, which is

commonly referred to as ‘the law of nervous shock’ . However, the second reason is, perhaps, less acceptable: the fear of the ﬂ  oodgates 
opening and admitting unacceptably large numbers of claims. It is worth pointing out that the ﬂ  oodgates argument, being only a 
spectre (but a highly inﬂ  uential one at that) and not overtly referred 
to by judges, has never been supported by hard empirical evidence. Nevertheless, the Law Commission, in its report on psychiatric injury claims supported the ﬂ  oodgates argument, largely on the 
basis of the lack of clear demarcation lines between general, uncom-pensatable, mental disturbance, and speciﬁ  c psychiatric illnesses. 
A third reason for the distinction between physical and psychiatric

A third reason for the distinction between physical and psychiatric 
injury is the argument that a too-liberal attitude might result in fraudulent claims. However, again there is no clear evidence to show that it is easy to fake psychiatric injury, and furthermore it is an odd system of justice which takes the approach that, because there is a possibility of fraud, genuine claims should fail.
It is important to note that in cases where the claimant has 
suffered physical injury, any claim for damages for associated psy-chiatric injury will not be controversial, subject to the claimant establishing causation. However, where the claim is for psychiatric injury alone special considerations apply and, it is worth summa-rizing the essential elements of such a claim. The distinction is often drawn between primary and secondary victims. A primary victim is either someone who is physically injured or is within the range of foreseeable physical injury (see Page  v. Smith ).

A secondary victim is someone who has some sort of proximity 
to one or more primary victims. (There are similarities in other European jurisdictions; for example in France this is dommage par 
ricochet , and the rules are more generous than in English-speaking 
jurisdictions.) In English law this has two aspects: ﬁ  rst, there 
must be close physical proximity to the trauma which injures or threatens the primary victim; second, the secondary victim must either have a close tie of love and affection with one or more of the primary victims, or he or she must be a rescuer of a primary victim and be within the range of foreseeable physical injury (see Alcock  v. 
Chief Constable of South Yorkshire Police ) and White  v. Chief 
Constable of South Yorkshire Police ). There is one other condition 
which a secondary victim must meet: the trauma must have the

which a secondary victim must meet: the trauma must have the 
necessary quality of ‘shockingness’ about it so as to make a sudden impact on the senses to such an extent that the person of normal fortitude must be shocked by it (the ‘impact rule’). Finally, in the cases of both primary and secondary victims, the negligence must result in a recognized psychiatric injury; emotional conditions such as grief, fear, and distress will not sufﬁ  ce. Of course, if the claimant 
has suffered distress as a result of physical injury, not amounting to a recognized psychiatric condition, then this should be reﬂ  ected in 
the damages for pain, suffering, and loss of amenity. Although ordinary ‘shock’ is not compensatable, both DSM-IV and ICD-10 refer to ‘acute stress reaction’ which, although only a short-term

1903
reaction to stress, should be compensatable as a recognized psychi-
atric condition, albeit that any compensation would be modest. (See Phelps  v. London Borough of Hillingdon , where it was held that 
the failure to mitigate the adverse consequences of a congenital defect such as dyslexia was capable of constituting an ‘injury’ .)
The impact rule states that the claimant must be present at the 
traumatic event or its immediate aftermath, and it must be an event such as to make an impact upon the unaided senses of the claim-ant, and to be shocking to a person of normal fortitude. The case of Sion v. Hampstead Health Authority  is illustrative of this point. The 
claimant was the father of a young man injured in a road accident. The defendant was the health authority because the father alleged that his son was treated negligently. The claimant watched his son deteriorate and die over a period of 14 days. The resultant psychiatric

illness suffered by the claimant was not compensatable as the 
process of death was slow, predictable, and not ‘shocking’ . This can be contrasted with Tredget and Tredget  v. Bexley Health Authority ,
which concerned the negligent delivery of a child, which took place in an atmosphere of ‘chaos’ and ‘pandemonium’ , and resulted in the child being born in a distressed state requiring immediate resusci-tation. The father, who was present at the birth, recovered damages for his subsequent psychiatric condition, as the event was sudden and impacted in a shocking way upon his senses. In Walters  v. North 
Glamorgan NHS Trust ) damages were awarded to a woman who 
spent 36 hours with her baby son from seeing him choking on blood and vomit to the termination of life support. This period was found to be a shocking series of events. However, in other jurisdic-tions the need to ﬁ  nd something sufﬁ  ciently shocking upon which 
to hang liability has been rejected. In the US case of Ochoa  v.

to hang liability has been rejected. In the US case of Ochoa  v. 
Superior Court (Santa Clara County) , a woman recovered damages 
when, despite her son begging her to stay, was forced to leave his hospital bedside on the basis that he only had ﬂ  u, and never saw 
him alive again. In Singapore, it was said that in the context of medical negligence as the secondary victim would rarely witness the act of negligence, it was wrong to impose the ‘shocking event’ requirement. Thus, in Pang Koi Fa  v. Lim Djoe Phing ) damages were 
awarded when a negligent medical procedure took place in June 1985 and the claimant watched her daughter die from then until the following September.
These sorts of distinctions are important in the context of 
so-called ‘creeping trauma’ in which there is no sudden impact to 
the senses. This refers to cases where victims have been exposed to

the senses. This refers to cases where victims have been exposed to 
some form of risk, for example contamination or the administra-tion of a drug which has caused no harmful effects yet, but which might do so. The absence of ‘impact’ might be thought to be fatal to such claims. However, in an Australian case ( AQP  v. Commonwealth 
Serum Laboratories Ltd ) the Victoria Supreme Court held that such 
cases should be decided on the basis of foreseeability and proximity alone. Subsequently this was conﬁ  rmed in an English decision,

cases should be decided on the basis of foreseeability and proximity alone. Subsequently this was conﬁ  rmed in an English decision, 
where a group of claimants had received the human growth hor-mone at a time when the Department of Health and the Medical Research Council was aware of the possibility of Creutzfeldt–Jakob disease contamination. They subsequently developed psychiatric illnesses through fear of contracting Creutzfeldt–Jakob disease, and recovered damages. At ﬁ  rst sight it may be thought that the impact 
rule would not apply because the claimants were primary victims. Although this is the common-sense view inasmuch as they had all been directly administered a drug, the judge was not willing to con-cede this. This was on the basis that it would widen unacceptably the number of potential primary victims in a much more wide-

spread case of possible contamination and would inhibit manufac-turers and providers of drugs and other goods from warning the public even when the risk was very small. Therefore the claimants were held to be secondary victims, but to whom a duty was owed simply on the basis of foreseeability. A duty of care was found to exist because of the nature of the relationship between the defend-ants and the claimants, the small and readily identiﬁ  able size of the 
group of claimants, the ways in which the claimants might become aware of the risk of Creutzfeldt–Jakob disease, and the nature of 
the suffering in terminal Creutzfeldt–Jakob disease.
(d) The liability of the mentally ill in negligence
It might be thought that if the law of negligence is about fault and

It might be thought that if the law of negligence is about fault and 
blame (as it is in the English-speaking jurisdictions, and some European jurisdictions as well), then those who have less apprecia-tion of risk and the consequences of their own actions might be regarded as being less culpable than those with a reasonable degree of appreciation. However, this is not the case. It is important to understand that, although the historical development of the law of tort suggests a number of different principles behind tort compen-sation and that in rare circumstances punitive damages can be recovered, generally tort is concerned with compensating victims rather than punishing wrongdoers. In the light of this it is not difﬁ cult to see why the same standard of care is applied. The second

reason for this is that courts do not want to apply a different stand-ard of care depending upon factors such as intelligence, emotional reactions, and experience. Therefore the standard is objective, being that of the reasonable person who is reasonably competent at what-ever task is being undertaken. (Note that there is an exception in the case of children who are judged in accordance with the reason-able foreseeability of the child of the relevant age.) The general principle is illustrated by the classic example of the learner driver who is expected to meet the standard of the reasonably competent driver (see the case of Nettleship  v. Weston ). In Wilsher  v. Essex Area 
Health Authority , in the Court of Appeal, Mustill LJ stated: ‘this

Health Authority , in the Court of Appeal, Mustill LJ stated: ‘this 
notion of a duty tailored to the actor rather than to the act which he elects to perform, has no place in the law of tort’ (the case subse-quently went to the House of Lords but this aspect of the judgment was undisturbed). However, there have been some exceptions to this (albeit not in England) which have interesting implications for the liability of the mentally ill. In the case of Cook  v. Cook , the High 
Court of Australia held that, in the case of an inexperienced driver, liability may be different depending on the identity of the defend-ant. For example, a car driver who injures a pedestrian will be sub-ject to the same standard of care as the reasonably competent driv-er, but when a driving instructor is injured, the fact that he knew of the claimant’s lack of experience might mean that there is no liability for his injuries. By analogy with Nettleship  v. Weston ,
(68) a mentally

(68) a mentally 
disordered person who negligently injures a third party will be sub-ject to the objective standard of care. These latter considerations, however, might have some relevance to the position of those who care for the mentally ill in that they might be expected to be aware of the increased likelihood of unstable behaviour. In other words, can it be argued, that if a patient negligently injures a doctor, nurse, or social worker, in the course of, say receiving treatment, then he might not be liable? It should be noted, however, that we are con-cerned with negligence, not deliberate acts, so this would not be a common scenario. Furthermore, the patient would very likely have 11.1 general principles of law relating to people with mental disorder

SECTION 11  forensic psychiatry 1904
few resources and no insurance so may not be worth suing. 
Nevertheless, if an action were ﬁ  nancially feasible, it may be that, 
for policy reasons, the courts would be unlikely to render someone in the position of a carer, without compensation. However, in Mansﬁ  eld  v. Weetabix Ltd , the Court of Appeal stated that in 
a case where the defendant could not reasonably have known about his condition, or the effect of it, there would be no liability.
(e) Liability to third parties for the acts of the mentally ill
The next question that arises is the extent, if any, of the liability of third parties for acts of the mentally ill, whether these are criminal or civil acts. The third party might be an individual who is caring for the defendant, but is much more likely to be a local authority or a health authority. This area of negligence has given rise to some emotive and controversial litigation. In Hill v. Chief Constable of

West Yorkshire Police  the House of Lords held that no liability 
attached to a police force that failed to arrest the serial killer Peter Sutcliffe before he killed his last victim. The decision did not turn upon whether there had been negligent conduct, but upon public policy. The interests of the public as a whole are best served, so runs the argument, if those responsible for public safety and so on are able to carry out their duties unfettered by the threat of litigation. It must be noted, however, that in the case of Osman  v. United 
Kingdom , this so-called immunity from suit was held by the 
European Court of Human Rights to be contrary to Article 6.1 of the European Convention on Human Rights (the protection of the right to a fair trial in both criminal and civil cases).
In Palmer v Tees Health Authority , the claimant, whose four year

In Palmer v Tees Health Authority , the claimant, whose four year 
old daughter was murdered by a psychopath, brought an action against the health authority, both in her own name as she had suf-fered from a psychiatric illness as a result of the murder, and on behalf of the child’s estate. Some months prior to committing the murder, the defendant had been an outpatient at the defendant’s psychiatric hospital, where he had allegedly told staff that he would kill a child. The Court of Appeal rejected her claims on the basis that there was not sufﬁ  cient proximity between the defendant and 
the victim. If, however, the defendant had known his victim and made threats speciﬁ  cally against her then there may well have been 
sufﬁ cient proximity to establish liability.
(f) Lia bility of the providers of services to the mentally ill
In the case of Clunis  v. Camden and Islington Health Authority ,

Clunis was a mentally disordered man who had been discharged from a psychiatric hospital and subsequently killed a man in an unprovoked attack. The prosecution accepted his plea of man-slaughter on the ground of diminished responsibility. Clunis subsequently sought damages from the health authority alleging that they had failed to treat him in accordance with their common-law duty of care, and that if he had been treated he would not have carried out the killing and would not have been subject to the lengthy period of detention he was now facing. The court invoked the legal maxim of ex turpi causa non oritur actio , which means that

they found that he could not establish a duty when it stemmed from the claimant’s own wrong-doing. The court relied on this as an aspect of public policy, and, somewhat curiously, referred to the 
importance of the deterrent effect of such a maxim. Given that the 
claimant was mentally ill, and the motiveless nature of the attack, he was surely incapable of being deterred? It is tempting to con-sider that Clunis  might have been decided differently in terms of 
ex turpi causa , if it had not also had implications for fettering the medical and resource-allocation discretion of health authorities to 
make them liable in negligence in this way.
It is well established that English health authorities can be both 
primarily liable (when there is an organizational failure) and vicar-
iously liable (where an individual employee is negligent) for acts of 
negligence. However, the provision of statutory duties by local authorities has raised some difﬁ  cult issues. The leading authority is

negligence. However, the provision of statutory duties by local authorities has raised some difﬁ  cult issues. The leading authority is 
X v. Bedfordshire County Council  In this case (a number of different 
cases listed together) the court had to consider the claims of claim-ants who alleged damage as a result of the negligence of social workers and psychiatrists involved in child protection cases, and teachers and others involved in the provision of education to children with special educational needs. Applying the threefold test from Caparo the court found that the ﬁ  rst two elements were 
satisﬁ  ed, that is foreseeability of damage and proximity of relation-
ship between the parties. However, on the third element, the ﬁ  nd-

ing was that it would not be ‘just and reasonable’ to impose a duty of care. In the context of child protection three reasons were given. First, the statutory system set up to protect children cuts across many disciplines: police, education bodies, doctors, and others. T o disentangle these relationships and to ascertain where the blame must fall would impose ‘impossible problems’ . Second, because there is a very ﬁ  ne balance to be drawn between the protection of 
children and the disruption of removing them from their homes, there is often a conﬂ  ict to be resolved. The professionals involved in

children and the disruption of removing them from their homes, there is often a conﬂ  ict to be resolved. The professionals involved in 
making such decisions should not be further hampered by the threat of litigation. Furthermore, a common-law liability may result in too cautious and defensive an approach on the part of local authorities. Finally, on a practical point, because of the obvious tensions between the local authority and the parents involved, litigation would be commonplace thereby placing a drain on 
vital resources necessary for the carrying out of the statutory functions.
However, if the social workers and psychiatrists involved person-
ally owed duties towards the claimants then, it was said, local 
authorities might be vicariously liable for any negligence on their part. Furthermore, the House of Lords speculated that educational services might be treated differently in that they were more in the nature of a ‘service to the public’ .

In Phelps  v. London Borough of Hillingdon
(60) the House of Lords 
conﬁ  rmed this approach. It concerned a claim for the failure of an 
educational psychologist to diagnose dyslexia. The court stated that vicarious liability arose on the basis of the personal duty owed by the psychologist, notwithstanding the fact that the educational psychology service was part of the general statutory services provided under the Educations Acts of 1944 and 1981, and that there would be no liability on the part of the local authority for breach of those statutory duties. A similar issue arose in the case of Clunis  v. Camden and Islington Health Authority
(73) (the facts of

(73) (the facts of 
which are outlined above). The court had to consider the extent of the after-care that should be provided under Section 117 of the Mental Health Act. Under this provision, there is a duty upon the district health authority and the local social services authority to provide after-care services for detained patients who leave hospital. It was alleged in this case that the psychiatrist responsible for mon-itoring the after-care of the claimant after discharge was negligent in failing to admit him to hospital, thereby preventing the act of homicide which followed. However, the Court of Appeal found that the services being provided by the psychiatrist after discharge

1905
were ‘essentially in the sphere of administrative activities in pursu-
ance of a scheme of social welfare in the community’ . These, it was stated, were different from the duties owed in the context of the doctor–patient relationship, and there was no common-law duty of care. Furthermore, under Section 124 of the Act, an allegation that inadequate Section 117 services are being provided should be dealt with by way of complaint to the Secretary of State. The court found that the wording of the statute indicated a parliamentary intention that breaches of Section 117 should not give rise to a cause of action in private law. In consequence, it seems that the outlook is bleak for claims resulting from the negligence of psychiatrists, psychologists, and social workers in the context of certain statutory functions of local authorities and health authorities alike.
It must be stressed that, although these cases are referring to

It must be stressed that, although these cases are referring to 
English statutory provisions, they raise general issues of principle as to how far statutory bodies are to be controlled by the courts, and, in particular, how far scarce public resources should be subject to depletion by litigation.
(g) Liability towards the mentally ill who harm themselves
As indicated above, the issues of consent to treatment, and compe-tence to both consent and refusal of treatment are central to many legal systems. The case of Re C  illustrates the importance of the 
right to self-determination in cases where, on the face of it, there might be a strong temptation to ﬁ  nd a patient incompetent because 
of the nature of the mental illness from which he suffers.
(22)
Under Section 63 of the Mental Health Act 1983, treatment can 
be given for mental disorder for which the patient is detained with-out the consent of the patient, and competency is irrelevant. In B v.

be given for mental disorder for which the patient is detained with-out the consent of the patient, and competency is irrelevant. In B v. 
Croydon Health Authority  treatment for mental disorder was
construed very widely. In that case the patient was clearly a ‘self-harmer’ , and force-feeding due to her refusal of food was held to be treatment for the mental disorder. If she had been incompetent, then treatment (of any sort, not just for the mental disorder) could have been administered in her best interests. The question then arises as to whether an incompetent patient not detained under the Act who, however, refuses food in an attempt to self-harm must be fed, failing which there would be a breach of the duty of care. It must be noted that the courts are extremely reluctant to question medical decisions about treatment. It is left to clinical judgement to 
decide whether to give, or withdraw, treatment (see the case of

decide whether to give, or withdraw, treatment (see the case of 
Airedale NHS Trust  v. Bland ). (In the same case it was conﬁ  rmed 
that treatment includes feeding; see also the Californian case of Bouvia  v. Superior Court .) The decision as to whether treatment is 
necessary is judged by reference to the Bolam test. In other words if there are good clinical reasons for treating or not treating, and these can be justiﬁ  ed by reference to a responsible body of medical 
opinion, then there will be no liability for failure to treat.
The question that arises is whether the health authority would 
have been liable nevertheless for failing to force-feed the subject of B v. Croydon Health Authority ,
(77) even though she was deemed 
capable of refusing treatment. It would follow from the general principle of self-determination, well established in English law (see, for example, Re T  (Adult: Refusal of Treatment ) and Re MB  (Adult: 
Medical Treatment ),

(23)) that such a refusal should be respected. 
However, recent case law in the context of the duty owed by prisons, and by implication hospitals, has considerably muddied the waters.In the case of Kirkham  v. Chief Constable of Greater Manchester 
Police  the court took the opportunity to look at the difference

Police  the court took the opportunity to look at the difference 
between negligent acts and negligent omissions (something that has exercised the minds of tort lawyers for some time) and said that, in this case, responsibility for the omission to prevent the sui-cide had been assumed by the defendant. The prisoner was said to be ‘of unsound mind’ , which presumably meant that, in the context of the right to self-determination, the prisoner was incapable of exercising his autonomy. In those circumstances the decision is not surprising on its facts. However, the judgment suggested that when one person is in the lawful custody of another, whether that be vol-untarily such as a hospital, or involuntarily such as a prison, there is a duty to take all reasonable steps to avoid acts or omissions to pre-vent reasonably foreseeable injury. Consequently in the case of Reeves  v. Commissioner of Police of the Metropolis , another custodial

suicide, the same duty was said to be owed to a ‘sane’ prisoner. Again, the wording is unfortunate by its reference to sanity, but it can be assumed that this prisoner was deemed to be competent. The police surgeon had stated, after examining the claimant, that there was no evidence of mental disturbance. It must be stressed that it will be necessary in all cases including those concerning hos-pitals, for there to be evidence that it was reasonable to regard the patient as a suicide risk. Of course, in practice, it may be the case that it is undesirable for hospitals to be venues for acts of suicide. However, it is by no means clear that, in the case of someone who has capacity, there should be a positive duty to prevent suicide any more than there should be a duty owed to prevent that person from smoking. These decisions are invoking a strong form of paternal ism.

Certainly in the case of hospital patients many competent patients discharge themselves against medical advice whereupon they are free to take any form of self-harming action. It is difﬁ  cult to see 
why there should be a positive duty to prevent the competent patient from carrying out the acts on hospital premises.
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1907
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Scope of this chapter
Offending is part of a larger syndrome of antisocial behaviour that 
arises in childhood and tends to persist into adulthood. There seems to be continuity over time, since the antisocial child tends to become the antisocial teenager and then the antisocial adult, just as the antisocial adult then tends to produce another antisocial child. The main focus of this chapter is on types of antisocial behaviour classiﬁ  ed as criminal offences, rather than on types classiﬁ  ed for 
example as conduct disorder or antisocial personality disorder.
In an attempt to identify causes, this chapter reviews risk 
factors that inﬂ  uence the development of criminal careers. Literally 
thousands of variables differentiate signiﬁ  cantly between ofﬁ  cial 
offenders and non-offenders and correlate significantly with reports of offending behaviour by young people. In this chapter, it is only possible to review brieﬂ  y some of the most important risk

offenders and non-offenders and correlate significantly with reports of offending behaviour by young people. In this chapter, it is only possible to review brieﬂ  y some of the most important risk 
factors for offending: individual difference factors such as high 
impulsivity and low intelligence, family inﬂ  uences such as poor 
child rearing and criminal parents, and social inﬂ  uences: socio-
economic deprivation, peer, school, community, and situational factors.
I will be very selective in focussing on some of the more impor-
tant and replicable findings obtained in some of the more methodologically adequate studies: especially prospective longitudinal follow-up studies of large community samples, with information from several data sources (e.g. the child, the parent, the teacher, ofﬁ  cial records) to maximize validity. The emphasis

is on offending by males; most research on offending has concen-trated on males, because they commit most of the serious predatory and violent offences. The review is limited to research carried out in the United Kingdom, the United States, and similar Western industrialized democracies. More extensive book length reviews of antisocial behaviour and offending are available elsewhere.
(1)
I will refer especially to knowledge gained in the Cambridge 
Study in Delinquent Development,(2) which is a prospective 
longitudinal survey of over 400 London males from age 8 to age 40. Fortunately, results obtained in British longitudinal surveys of delinquency are highly concordant with those obtained in comparable surveys in North America, the Scandinavian countries, and New Zealand and indeed with results obtained in British cross-

sectional surveys. A systematic comparison of the Cambridge Study with the Pittsburgh Y outh Study showed numerous replicable predictors of offending over time and place, including impulsivity, attention problems, low school attainment, poor parental supervi-sion, parental conﬂ  ict, an antisocial parent, a young mother, large 
family size, low family income, and coming from a broken family.
Measurement and epidemiology
Offending is defined as acts prohibited by the criminal law, such as theft, burglary, robbery, violence, vandalism, and drug use. It is commonly measured using either ofﬁ  cial records of 
arrests or convictions or self-reports of delinquency. The advantages and disadvantages of ofﬁ  cial records and self-reports 
are to some extent complementary. In general, ofﬁ  cial records

are to some extent complementary. In general, ofﬁ  cial records 
identify the worst offenders and the worst offences, while self-reports include more of the normal range of delinquent activity. The worst offenders may be missing from samples interviewed in self-report studies. Self-reports have the advantage of including undetected offences, but the disadvantages of concealment and forgetting. By normally accepted psychometric criteria of validity, self-reports are valid. Self-reported delinquency predicted later convictions in the Cambridge Study. In the Pittsburgh 
Y outh Study,
(3) the seriousness of self-reported delinquency 
predicted later court referrals. However, predictive validity was enhanced by combining self-report, parent, and teacher informa-tion about offending.
The key issue is whether the same results are obtained with both

The key issue is whether the same results are obtained with both 
methods. For example, if ofﬁ  cial records and self-reports both show 
a link between parental supervision and delinquency, it is likely that supervision is related to delinquent behaviour (rather than to any biases in measurement). Generally, the worst offenders accord-ing to self-reports (taking account of frequency and seriousness) tend also to be the worst offenders according to ofﬁ  cial records. 
In the Cambridge Study between ages 15 and 18, 11 per cent of the males admitted burglary, and 62 per cent of these males were convicted of burglary. The predictors and correlates of ofﬁ  cial and 
self-reported delinquency were very similar.
Much is known about the epidemiology and development of 
offending and criminal careers, but there is not space to review these topics here.
(4) For example, the prevalence of offending tends Psychosocial causes 
of offending
David P . Farrington11.2

1909
to peak in the teenage years, and an early onset of offending pre-
dicts a long criminal career. Offenders tend to be versatile rather than specialized, in committing not only different types of offences but also different types of other antisocial acts. While there is con-siderable continuity over time, in the sense that the most antisocial people at one age tend also to be the most antisocial at another, only about half of antisocial juveniles tend to become antisocial adults.
A risk factor is deﬁ  ned as a variable that predicts an increased risk 
of offending. For example, children who experience poor parental supervision have an increased risk of committing offences later on. Since risk factors are deﬁ  ned by their ability to predict later

of offending. For example, children who experience poor parental supervision have an increased risk of committing offences later on. Since risk factors are deﬁ  ned by their ability to predict later 
offending, it follows that longitudinal data are required to discover them. Risk factors tend to be similar for many different outcomes, including violent and non-violent offending, mental health prob-lems, alcohol and drug problems, school failure, and unemploy-ment. Protective factors are also important. They are deﬁ  ned as 
factors that predict a low risk of offending or that counteract risk factors.
An obvious problem is that it is not clear to what extent any risk 
factor is a cause of offending. It is important to investigate causal mechanisms linking risk factors and offending. The best way of establishing a cause is to carry out a prevention experiment tackling 
that risk factor; preferably a randomized experiment, because the

that risk factor; preferably a randomized experiment, because the 
random assignment of people to conditions in principle controls for all other inﬂ  uences on offending. If a prevention experiment 
was carried out in which parental supervision was improved, and if offending was reduced as a consequence, this would be powerful evidence that the risk factor of parental supervision truly had a causal effect on offending. However, most knowledge about causes comes from quasi-experimental analyses.
Because of the difﬁ  culty of establishing causal effects of factors 
that vary only between individuals (e.g. gender and ethnicity), and because such factors have no practical implications for prevention (e.g. it is not practicable to change males into females), unchanging variables will not be reviewed here. In any case, their effects on offending are usually explained by reference to other, modiﬁ  able,

factors. For example, gender differences in offending have been explained on the basis of different socialization methods used by parents with boys and girls, or different opportunities for offend-ing by men and women. Similarly, risk factors that are or might be measuring the same underlying construct as delinquency (e.g. physical aggression) will not be reviewed; the focus is on risk fac-tors that might be causes. For simplicity, risk factors are reviewed one by one. Biological factors are not reviewed. I will not attempt to review additive, interactive, independent, or sequential effects of risk factors, although these are important issues. Nor will I review developmental theories of offending.
Individual factors
Hyperactivity and impulsivity
Hyperactivity and impulsivity are among the most important personality or individual difference factors that predict later offending.
(5) Hyperactivity usually begins before age 5 and often

(5) Hyperactivity usually begins before age 5 and often 
before age 2, and it tends to persist into adolescence. It is associated with restlessness, impulsivity and a short attention span, and for 
that reason has been termed the ‘hyperactivity-impulsivity-attention deﬁ cit’ or HIA syndrome. Related concepts include a poor ability to 
defer gratiﬁ  cation and a short future time perspective.
Many investigators have reported a link between hyperactivity or 
impulsivity and offending. For example, in the Orebro (Sweden) longitudinal survey,
(6) hyperactivity at age 13 (rated by teachers) 
predicted violent offending up to age 26. The highest rate of violence was among males with both motor restlessness and concentration difﬁ  culties. The most extensive research on different

predicted violent offending up to age 26. The highest rate of violence was among males with both motor restlessness and concentration difﬁ  culties. The most extensive research on different 
measures of impulsivity was carried out by Jennifer White and her colleagues in the Pittsburgh Y outh Study. This showed that cognitive or verbal impulsivity (e.g. acts without thinking, unable to defer gratiﬁ  cation) was more strongly related to delinquency 
than was behavioural impulsivity (e.g. clumsiness in psychomotor tests).
In the Cambridge Study, a combined measure of hyperactivity-
impulsivity-attention deﬁ  cit was developed at age 8–10, and it sig-
niﬁ cantly predicted juvenile convictions independently of conduct 
problems at age 8–10. Hence, HIA is not merely another measure of antisocial personality, but it is a possible cause, or an earlier stage 
in a developmental sequence leading to offending. Similar con-

structs to hyperactivity, such as sensation seeking, are also related to delinquency. In the Cambridge Study, the extent to which the boy was daring or took risks at age 8–10, as well as restlessness and poor concentration, signiﬁ  cantly predicted convictions and high 
self-reported offending. Daring was consistently one of the strong-est independent predictors of offending.
Low intelligence and attainment
Low intelligence is an important predictor of offending, and it can be measured very early in life. In a prospective longitudinal survey of about 120 Stockholm males,
(7) low IQ measured at age 3, 
signiﬁ  cantly predicted ofﬁ  cially recorded offending up to age 30.

signiﬁ  cantly predicted ofﬁ  cially recorded offending up to age 30. 
Frequent offenders (with 4 or more offences) had an average IQ of 88 at age 3, whereas non-offenders had an average IQ of 101. All of these results held up after controlling for social class. Similarly, low IQ at age 4 predicted arrests up to age 27 in the Perry preschool project.
(8)
In the Cambridge Study, twice as many of the boys scoring 90 or 
less on a non-verbal IQ test (Raven’s Progressive Matrices) at age 8–10 were convicted as juveniles as of the remainder. However, it was difﬁ  cult to disentangle low intelligence and low school attain-

ment. Low non-verbal intelligence was highly correlated with low verbal intelligence (vocabulary, word comprehension, verbal reasoning) and with low school attainment, and all of these meas-ures predicted juvenile convictions to much the same extent. In addition to their poor school performance, delinquents tended to leave school at the earliest possible age (which was then 15) and to take no school examinations.
Low non-verbal intelligence predicted juvenile self-reported 
offending to almost exactly the same degree as juvenile convictions, suggesting that the link between low intelligence and delinquency 
was not caused by the less intelligent boys having a greater proba-
bility of being caught. Also, measures of intelligence and attain-ment predicted measures of offending independently of other variables such as family income and family size. Delinquents often do better on non-verbal performance tests, such as object assembly 11.2 psychosocial causes of offending

SECTION 11  forensic psychiatry 1910
and block design, than on verbal tests, suggesting that they ﬁ  nd it 
easier to deal with concrete objects than with abstract concepts.
Low IQ may lead to delinquency through the intervening

Low IQ may lead to delinquency through the intervening 
factor of school failure; the association between school failure and delinquency has been demonstrated consistently in longitudinal surveys. In the Pittsburgh Y outh Study, Donald Lynam and his colleagues concluded that low verbal IQ led to school failure and subsequently to self-reported delinquency, but only for African-American boys. Another plausible explanatory factor underlying the link between low IQ and delinquency is the ability to manipu-late abstract concepts. Children who are poor at this tend to do badly in IQ tests and in school attainment and they also tend to commit offences, mainly because of their poor ability to foresee the consequences of their offending and to appreciate the feelings of victims. Low IQ may be one aspect of cognitive and neuropsy-chological deﬁ  cits in the executive functions of the brain.
Family factors
Child rearing

Many different types of child-rearing methods predict offending. 
The most important dimensions of child rearing are supervision or monitoring of children, discipline or parental reinforcement, warmth or coldness of emotional relationships, and parental involvement with children. Parental supervision refers to the degree of monitoring by parents of the child’s activities, and their degree of watchfulness or vigilance. Of all these child-rearing methods, poor parental supervision is usually the strongest and most replica-ble predictor of offending. Many studies show that parents who do not know where their children are when they are out, and parents who let their children roam the streets unsupervised from an early age, tend to have delinquent children. For example, in Joan McCord’s classic Cambridge–Somerville Study in Boston,
(9) poor 
parental supervision in childhood was the best predictor of both violent and property crimes up to age 45.

(9) poor 
Parental discipline refers to how parents react to a child’s 
behaviour. It is clear that harsh or punitive discipline (involving physical punishment) predicts offending. In their follow-up study of nearly 700 Nottingham children, John and Elizabeth Newson
(10)
found t hat physical punishment at ages 7 and 11 predicted later 
convictions; 40 per cent of offenders had been smacked or beaten at age 11, compared with 14 per cent of non-offenders. Erratic or inconsistent discipline also predicts delinquency. This can involve either erratic discipline by one parent, sometimes turning a blind eye to bad behaviour and sometimes punishing it severely, or incon-sistency between  two parents, with one parent being tolerant or 
indulgent and the other being harshly punitive.
Cold, rejecting parents tend to have delinquent children, as Joan

Cold, rejecting parents tend to have delinquent children, as Joan 
McCord found in the Cambridge–Somerville Study. More recently, she concluded that parental warmth could act as a protective factor against the effects of physical punishment. Whereas 51 per cent of boys with cold physically punishing mothers were convicted in her study, only 21 per cent of boys with warm physically punishing 
mothers were convicted, similar to the 23 per cent of boys with warm 
non-punitive mothers who were convicted. The father’s warmth was also a protective factor against the father’s physical punishment.
Most explanations of the link between child-rearing methods 
and delinquency focus on attachment or social learning theories. Attachment theory was inspired by the work of John Bowlby, and suggests that children who are not emotionally attached to warm, loving, and law-abiding parents tend to become offenders. Social

learning theories suggest that children’s behaviour depends on parental rewards and punishments and on the models of behaviour that parents represent. Children will tend to become offenders if parents do not respond consistently and contingently to their anti-social behaviour and if parents themselves behave in an antisocial manner.
Teenage mothers and child abuse
At least in Western industrialized countries, early child-bearing, or teenage pregnancy, predicts many undesirable outcomes for the children, including low school attainment, antisocial school behaviour, substance use, and early sexual intercourse. The children of teenage mothers are also more likely to become offenders. For example, Morash and Rucker
(11) analysed results from four surveys

(11) analysed results from four surveys 
in the United States and the United Kingdom (including the Cambridge Study) and found that teenage mothers were associated with low income families, welfare support, and absent biological fathers, that they used poor child-rearing methods, and that their children were characterized by low school attainment and delin-quency. However, the presence of the biological father mitigated many of these adverse factors and generally seemed to have a pro-tective effect. In the Cambridge Study, teenage mothers who went on to have large numbers of children were especially likely to have convicted children. In the Newcastle Thousand-Family Study
(12)
mothers who married as teenagers (a factor strongly related to teenage childbearing) were twice as likely as others to have sons who became offenders by age 32.
There is considerable intergenerational transmission of aggres-
sive and violent behaviour from parents to children, as Maxﬁ  eld 
and Widom

and Widom
(13) found in a retrospective study of over 900 abused 
children in Indianapolis. Children who were physically abused up to age 11 were signiﬁ  cantly likely to become violent offenders in 
the next 15 years. In the Cambridge–Somerville Study in Boston, Joan McCord found that about half of the abused or neglected boys were convicted for serious crimes, became alcoholics or mentally ill, or died before age 35. In the Rochester Y outh Development Study,
(14) child maltreatment under age 12 (physical, sexual or 
emotional abuse or neglect) predicted later self-reported and ofﬁ  cial 
offending. Furthermore, these results held up after controlling for gender, race, socio-economic status, and family structure.
Numerous theories have been put forward to explain the link

Numerous theories have been put forward to explain the link 
between child abuse and later offending. Timothy Brezina described three of the main ones.
(15) Social learning theory suggests that chil-
dren learn to adopt the abusive behaviour patterns of their parents through imitation, modelling, and reinforcement. Attachment or social bonding theory proposes that child maltreatment results in low attachment to parents and hence to low self-control. Strain theory posits that negative treatment by others generates negative emotions such as anger and frustration, which in turn lead to a desire for revenge and increased aggression. Based on analyses of the Y outh in Transition Study, Brezina found limited support for all three theories.
Parental conﬂ  ict and disrupted families
Many studies show that broken homes or disrupted families

Many studies show that broken homes or disrupted families 
predict offending. In the Newcastle Thousand-Family Study, marital disruption (divorce or separation) in a boy’s ﬁ  rst 5 years 
doubled his risk of later convictions up to age 32. Similarly, in the Dunedin Study in New Zealand,
(16) children who were exposed

1911
to parental discord and many changes of the primary caretaker 
tended to become antisocial and delinquent. The same study 
showed that single parent families disproportionally tended to have convicted sons; 28 per cent of violent offenders were from single parent families, compared with 17 per cent of non-violent offenders and 9 per cent of unconvicted boys.
The importance of the cause of the broken home is shown in the 
UK National Survey of Health and Development.
(17) Boys from 
homes broken by divorce or separation had an increased likelihood of being convicted or ofﬁ  cially cautioned up to age 21, in comparison

homes broken by divorce or separation had an increased likelihood of being convicted or ofﬁ  cially cautioned up to age 21, in comparison 
with those from homes broken by death or from unbroken homes. Homes broken while the boy was under age 5 especially predicted offending, whereas homes broken while the boy was between ages 11 and 15 were not particularly criminogenic. Remarriage (which happened more often after divorce or separation than after death) was also associated with an increased risk of offending, suggesting a possible negative effect of step-parents. The meta-analysis by Wells and Rankin
(18) also shows that broken homes are more 
strongly related to delinquency when they are caused by parental separation or divorce rather than by death.
Most studies of broken homes have focussed on the loss of the

Most studies of broken homes have focussed on the loss of the 
father rather than the mother, simply because the loss of a father is much more common. Joan McCord in Boston carried out an interesting study of the relationship between homes broken by loss of the natural father and later serious offending of the children. She found that the prevalence of offending was high for boys reared in broken homes without affectionate mothers (62 per cent) and for those reared in united homes characterized by parental conﬂ  ict 
(52 per cent), irrespective of whether they had affectionate mothers. The prevalence of offending was low for those reared in united homes without conﬂ  ict (26 per cent) and—importantly—
equally low for boys from broken homes with affectionate mothers (22 per cent). These results suggest that it is not so much the

equally low for boys from broken homes with affectionate mothers (22 per cent). These results suggest that it is not so much the 
broken home which is criminogenic as the parental conﬂ  ict which 
often causes it, and that a loving mother might in some sense be able to compensate for the loss of a father.
In the Cambridge Study, both permanent and temporary separa-
tions from a biological parent before age 10 (usually from the father) predicted convictions and self-reported delinquency, providing that they were not caused by death or hospitalization. However, homes broken at an early age (under age 5) were not unusually criminogenic. Separation before age 10 predicted both juvenile and adult convictions, independently of all other factors such as low family income or poor school attainment, and was an important predictor of adult social dysfunction.
Explanations of the relationship between disrupted families and

Explanations of the relationship between disrupted families and 
delinquency fall into three major classes. Trauma theories suggest that the loss of a parent has a damaging effect on a child, most commonly because of the effect on attachment to the parent. Life course theories focus on separation as a sequence of stressful expe-
riences, and on the effects of multiple stressors such as parental 
conﬂ  ict, parental loss, reduced economic circumstances, changes in 
parent ﬁ  gures, and poor child-rearing methods. Selection theories 
argue that disrupted families produce delinquent children because of pre-existing differences from other families in risk factors such as parental conﬂ  ict, criminal or antisocial parents, low family 
income, or poor child-rearing methods.
Hypotheses derived from the three theories were tested in the 
Cambridge Study.
(19) While boys from broken homes (permanently

(19) While boys from broken homes (permanently 
disrupted families) were more delinquent than boys from intact homes, they were not more delinquent than boys from intact high 
conﬂ  ict families. Overall, the most important factor was the post-
disruption trajectory. Boys who remained with their mother after the separation had the same delinquency rate as boys from intact low conﬂ  ict families. Boys who stayed with their father, with rela-
tives, or with others (e.g. foster parents) had high delinquency rates. These living arrangements were more unstable, and other research shows that frequent changes of parent ﬁ  gures predict 
offending. It was concluded that the results favoured life course theories rather than trauma or selection theories
Criminal parents

Lee Robins and her colleagues showed that criminal, antisocial and alcoholic parents tend to have delinquent sons.
(20) She followed up 
over 200 males in St. Louis and found that arrested parents tended to have arrested children, and that the juvenile records of the parents and children had similar rates and types of offences. Joan McCord also reported that convicted fathers tended to have convicted sons. She found that 29 per cent of fathers convicted for violence had sons convicted for violence, in comparison with 12 per cent of other fathers, but this may reﬂ  ect the general tend-
ency for convicted fathers to have convicted sons rather than any speciﬁ  c tendency for violent fathers to have violent sons.
In the Cambridge Study, the concentration of offending in a

In the Cambridge Study, the concentration of offending in a 
small number of families was remarkable. Less than 6 per cent of the families were responsible for half of the criminal convictions of all members (fathers, mothers, sons, and daughters) of all 
400 families. Having a convicted mother, father, brother, or sister signiﬁ  cantly predicted a boy’s own conviction. As many as 63 per cent 
of boys with a convicted parent were themselves convicted up to age 40. Furthermore, convicted parents and delinquent siblings predicted self-reported as well as to ofﬁ  cial offending. Same-sex 
relationships were stronger than opposite-sex relationships, and older siblings were stronger predictors than younger siblings. Therefore, there is intergenerational continuity in offending.
It is not entirely clear why criminal parents tend to have delin-

quent children. In the Cambridge Study, there was no evidence that criminal parents directly encouraged their children to commit crimes or taught them criminal techniques. On the contrary, crim-inal parents were highly critical of their children’s offending; for example, 89 per cent of convicted men at age 32 disagreed with the statement that ‘I would not mind if my son/daughter committed a criminal offence’ . Also, it was extremely rare for a parent and a child to be convicted for an offence committed together. The main link in the chain between criminal parents and delinquent sons seemed to be poor parental supervision.
There are several possible explanations (which are not mutually

There are several possible explanations (which are not mutually 
exclusive) for why offending tends to be concentrated in certain families and transmitted from one generation to the next. First, there may be intergenerational continuities in exposure to multiple risk factors. For example, each successive generation may be entrapped in poverty, disrupted families, single and/or teenage parenting, and living in the most deprived neighbourhoods. Second, the effect of a criminal parent on a child’s offending may 
be mediated by environmental mechanisms such as poor parental 
supervision. Third, the effect of a criminal parent on a child’s offending may be mediated by genetic mechanisms. Fourth, criminal parents may tend to have delinquent children because of ofﬁ  cial (police and court) bias against criminal families, who 
also tend to be known to ofﬁ  cial agencies because of other social 11.2 psychosocial causes of offending

SECTION 11  forensic psychiatry 1912
problems. At all levels of self-reported delinquency in the 
Cambridge Study, boys with convicted fathers were more likely to 
be convicted themselves than were boys with unconvicted fathers. However, this was not the only explanation for the link between criminal fathers and delinquent sons, because boys with criminal fathers had higher self-reported delinquency scores and higher teacher and peer ratings of bad behaviour.
Large family size
Large family size (a large number of children in the family) is a relatively strong and highly replicable predictor of offending. It was similarly important in the Cambridge and Pittsburgh studies,
(21)

(21)
even though families were on average smaller in Pittsburgh in the 1990s than in London in the 1960s. In the Cambridge Study, if a boy had four or more siblings by his tenth birthday, this doubled his risk of being convicted as a juvenile, and large family size pre-dicted self-reported offending as well as convictions. It was the most important independent predictor of convictions up to age 32 in a logistic regression analysis.
In the National Survey of Health and Development, Michael 
Wadsworth found that the percentage of boys who were convicted increased from 9 per cent for families containing one child to 24 per cent for families containing four or more children. The Newsons in their Nottingham study also concluded that large family size was one of the most important predictors of offending. 
A similar link between family size and antisocial behaviour was 
reported by Israel Kolvin and his colleagues in their follow-up of Newcastle children from birth to age 33.

There are many possible reasons why a large number of siblings 
might increase the risk of a child’s offending. Generally, as the number of children in a family increases, the amount of parental attention that can be given to each child decreases. Also, as the number of children increases, the household tends to become more overcrowded, possibly leading to increases in frustration, irri-tation, and conﬂ  ict. In the Cambridge Study, large family size 
did not predict delinquency for boys living in the least crowded conditions. This suggests that household overcrowding might be an important intervening factor between large family size and delinquency.
Brownﬁ  eld and Sorenson
(22) reviewed several possible explana-

tions for the link between large families and delinquency, including those focussing on features of the parents (e.g. criminal parents, teenage parents), those focussing on parenting (e.g. poor super-vision, disrupted families), and those focussing on economic deprivation or family stress. Another interesting theory suggested that the key factor was birth order: large families include more later-born children, who tend to be more delinquent. Based on an analysis of self-reported delinquency in a Seattle survey, they concluded that the most plausible intervening causal mechanism was exposure to delinquent siblings. In the Cambridge Study, co-offending by brothers was surprisingly common; about 20 per cent of boys who had brothers close to them in age, were convicted for a crime committed with their brother.
Social factors
Socio-economic deprivation

The voluminous literature on the relationship between socio-economic status (SES) and offending is characterized by inconsist-encies and contradictions, and some reviewers
(23) have concluded that there is no relationship between SES and either self-reported 
or ofﬁ  cial offending. British studies have reported more consistent 
links between low social class and offending. In the UK National Survey of Health and Development, the prevalence of ofﬁ  cial 
juvenile delinquency in males varied considerably according to the 
occupational prestige and educational background of their parents, from 3 per cent in the highest category to 19 per cent in the lowest. It has been suggested that low SES families tend to produce delin-quent children because their child-rearing tends to be poor.
Numerous indicators of SES were measured in the Cambridge

Numerous indicators of SES were measured in the Cambridge 
Study, both for the boy’s family of origin and for the boy himself as an adult, including occupational prestige, family income, housing, and employment instability. Most of the measures of occupational prestige (based on the Registrar General’s scale) were not signiﬁ  -
cantly related to offending. Low SES of the family when the boy was aged 8–10 signiﬁ  cantly predicted his later self-reported but not 
his ofﬁ  cial delinquency. More consistently, low family income and 
poor housing predicted ofﬁ  cial and self-reported, juvenile and 
adult, offending.
It was interesting that the peak age of offending, at 17–18, coin-
cided with the peak age of afﬂ  uence for many convicted males. 
In the Cambridge Study, convicted males tended to come from low 
income families at age 8 and later tended to have low incomes themselves at age 32. However, at age 18, they were relatively well

income families at age 8 and later tended to have low incomes themselves at age 32. However, at age 18, they were relatively well 
paid in comparison with non-delinquents. Whereas convicted delinquents might be working as unskilled labourers on building sites and getting the full adult wage for this job, non-delinquents might be in poorly paid jobs with prospects, such as bank clerks, or might still be students. These results show that the link between income and offending is quite complex.
Socio-economic deprivation of parents is usually compared with

Socio-economic deprivation of parents is usually compared with 
offending by children. However, when the children grow up, their own socio-economic deprivation can be related to their own offending. In the Cambridge Study, an unstable job record of the boy at age 18 was one of the best independent predictors of his later convictions between ages 21 and 25. Also, having an unskilled manual job at age 18 was an important independent predictor of adult social dysfunction and antisocial personality at age 32.
Between ages 15 and 18, the study boys were convicted at a high-
er rate when they were unemployed than when they were employed, suggesting that unemployment in some way causes crime, and con-versely that employment may lead to desistance from offending.
(24)
Since crimes involving material gain (e.g. theft, burglary, robbery) especially increased during periods of unemployment, it seems likely that ﬁ  nancial need is an important link in the causal chain

between unemployment and crime.
Having delinquent friends is an important predictor of later 
offending; peer delinquency and gang membership predicted self-reported violence in the Seattle Social Development Project.
(25)
Delinquent acts tend to be committed in small groups (of two or three people, usually) rather than alone. Large gangs are com-paratively unusual. In the Cambridge Study, the probability of committing offences with others decreased steadily with age. Before age 17, boys tended to commit their crimes with other boys similar in age and living close by. After age 17, co-offending became less common.
(26)
The major problem of interpretation is whether young people 
are more likely to commit offences while they are in groups than

1913
while they are alone, or whether the high prevalence of co-offending 
merely reﬂ  ects the fact that, whenever young people go out, they 
tend to go out in groups. Do peers tend to encourage and facilitate offending, or is it just that most kinds of activities out of the home (both delinquent and non-delinquent) tend to be committed in groups? Another possibility is that the commission of offences encourages association with other delinquents, perhaps because ‘birds of a feather ﬂ  ock together’ or because of the stigmatizing and 
isolating effects of court appearances and institutionalization. T erence Thornberry and his colleagues in the Rochester Y outh Development Study concluded that there were reciprocal effects, with delinquent peers causing de linquency and de linque ncy causing
association with delinquent peers.
In the Pittsburgh Y outh Study, the relationship between peer

In the Pittsburgh Y outh Study, the relationship between peer 
delinquency and a boy’s offending was studied both between individuals (e.g. comparing peer delinquency and offending of boy X with peer delinquency and offending of boy Y at a particular age and then aggregating these correlations over all ages) and with-in individuals (e.g. comparing peer delinquency and offending of boy X at different ages and then aggregating these correlations over all individuals). Peer delinquency was the strongest correlate of offending in between-individual correlations but did not predict offending within individuals.
(27) In contrast, poor parental super-

vision, low parental reinforcement, and low involvement of the boy in family activities predicted offending both between and within individuals. It was concluded that these three family variables were the most likely to be causes, whereas having delinquent peers was most likely to be an indicator of the boy’s offending.
Associating with delinquent friends at age 14 was an important 
independent predictor of convictions at the young adult ages in the Cambridge Study. Also, the recidivists at age 19 who ceased offending differed from those who persisted, in that the desisters were more likely to have stopped going round in a group of male friends. Furthermore, spontaneous comments by the youths indicated that withdrawal from the delinquent peer group was an important inﬂ  uence on ceasing to offend. Therefore, continuing 
to associate with delinquent friends may be a key factor in deter-

mining whether juvenile delinquents persist in offending as young adults or desist.
School inﬂ  uences
The prevalence of delinquency among students varies dramatically 
between different secondary schools, as Michael Power and his colleagues
(28) showed many years ago in London. Characteristics 
of high delinquency-rate schools are well-known. For example, such schools have high levels of distrust between teachers and students, low commitment to school by students, and unclear and inconsistently enforced rules. However, what is far less clear is how much of the variation between schools should be attributed to differences in school organization, climate and practices, and how much to differences in the composition of the student body.
In the Cambridge Study, attending a high delinquency-rate 
school at age 11 signiﬁ  cantly predicted a boy’s later offending and

school at age 11 signiﬁ  cantly predicted a boy’s later offending and 
antisocial personality scores. The effects of secondary schools on delinquency were investigated by following boys from their primary schools to their secondary schools. The best primary school predictor of juvenile delinquency was the rating of the boy’s troublesomeness at age 8–10 by peers and teachers, showing the continuity in antisocial behaviour. The secondary schools differed dramatically in their ofﬁ  cial delinquency rates, from one school with 21 court appearances per 100 boys per year to another where 
the corresponding ﬁ  gure was only 0.3. Moreover, going to a high 
delinquency-rate secondary school was a signiﬁ  cant predictor of

delinquency-rate secondary school was a signiﬁ  cant predictor of 
later convictions. It was, however, very noticeable that the most troublesome boys tended to go to the high delinquency-rate schools, while the least troublesome boys tended to go to the low delinquency-rate schools. Most of the variation between schools in their delinquency rates could be explained by differences in their intakes of troublesome boys. The secondary schools themselves had only a very small effect on the boys’ offending.
The most famous study of school effects on delinquency was also 
carried out in London, by Michael Rutter and his colleagues.
(29)

(29)
They studied 12 comprehensive schools, and again found big differences in official delinquency rates between them. High delinquency-rate schools tended to have high truancy rates, low ability pupils, and low social class parents. However, the differences between the schools in delinquency rates could not be entirely explained by differences in the social class and verbal reasoning scores of the pupils at intake (age 11). Therefore, they must have been caused by some aspect of the schools themselves or by other, unmeasured factors.
In trying to discover which aspects of schools might be encour-
aging or inhibiting offending, Rutter and his colleagues found that the main school factors that were associated with delinquency were a high amount of punishment and a low amount of praise given by 
teachers in class. Unfortunately, it is difﬁ  cult to know whether

teachers in class. Unfortunately, it is difﬁ  cult to know whether 
much punishment and little praise are causes or consequences of antisocial school behaviour, which in turn may be linked to offending outside school. In regard to other outcome measures, they argued that an academic emphasis, good classroom manage-ment, the careful use of praise and punishment, and student participation were important features of successful schools.
Community inﬂ  uences
Offending rates vary systematically with area of residence. For 
example, the classic studies by Shaw and McKay(30) in Chicago and

example, the classic studies by Shaw and McKay(30) in Chicago and 
other American cities showed that juvenile delinquency rates (based on where offenders lived) were highest in inner city areas characterized by physical deterioration, neighbourhood disorgani-zation, and high residential mobility. A large proportion of all offenders came from a small proportion of areas, which tended to be the most deprived. Furthermore, these relatively high delin-quency rates persisted over time, despite the effect of successive waves of immigration and emigration of different national and ethnic groups in different areas.
Living in a deprived neighbourhood (whether based on parent 
ratings or on census measures of poverty, unemployment and female-headed households) signiﬁ  cantly predicts convictions and 
self-reported offending. However, it is difﬁ  cult to establish how

self-reported offending. However, it is difﬁ  cult to establish how 
much the areas themselves inﬂ  uence antisocial behaviour and how 
much it is merely the case that antisocial people tend to live in deprived areas (e.g. because of their poverty or public housing allocation policies). It has been suggested that neighbourhoods have only indirect effects on offending because of their effects on individuals and families. However, Robert Sampson and his colleagues
(31) argued that a low degree of ‘collective efﬁ  cacy’ of a 
neighbourhood (a low degree of informal social control) caused high crime rates.
One key question is why crime rates of communities change over 
time, and to what extent this is a function of changes in the 11.2 psychosocial causes of offending

SECTION 11  forensic psychiatry 1914
communities or in the individuals living in them. Answering this 
question requires longitudinal research in which both communi-ties and individuals are followed up. The best way of establishing the impact of the environment is to follow people who move from one area to another. For example, in the Cambridge Study, moving out of London led to a signiﬁ  cant decrease in convictions and 
self-reported offending. This decrease may have occurred because moving out led to a breaking up of co-offending groups, or because there were fewer opportunities for crime outside London.
Situational inﬂ  uences
It might be argued that all the risk factors reviewed so far in this 
section—individual, family, socio-economic, peer, school, and community—essentially inﬂ  uence the development of a long-term

section—individual, family, socio-economic, peer, school, and community—essentially inﬂ  uence the development of a long-term 
individual potential for offending. In other words, they contribute to between-individual differences: why some people are more likely than others, given the same situational opportunity, to commit a crime. Another set of inﬂ  uences—situational factors—explain how 
the potential for violence becomes the actuality in any given situation. Essentially, they explain short-term within-individual differences: why a person is more likely to commit crimes in some situations than in others. Situational factors may be speciﬁ  c to par-
ticular types of crimes: robberies as opposed to rapes, or even street robberies as opposed to bank robberies.
The most popular theory of offending events is a rational choice 
theory suggesting that they occur in response to speciﬁ  c opportu-

nities, when their expected beneﬁ  ts (e.g. stolen property, peer 
approval) outweigh their expected costs (e.g. legal punishment, parental disapproval). For example, Clarke and Cornish
(32) sug-
gested that residential burglary depended on such inﬂ  uencing 
factors as whether a house was occupied, whether it looked afﬂ uent, whether there were bushes to hide behind, whether there 
were nosy neighbours, whether the house had a burglar alarm, and whether it contained a dog. A related theory is the ‘routine activities’ idea of Cohen and Felson.
(33) They suggested that, for a 
predatory crime to occur, the minimum requirement was the convergence in time and place of a motivated offender and a suita-ble target, in the absence of a capable guardian. They argued that predatory crime rates were inﬂ  uenced by routine activities that

satisﬁ  ed basic needs such as food and shelter. Changes in routine 
activities led to changing opportunities for crime. For example, the increasing number of working women meant that more homes were left unattended during the day.
Much work on describing situations leading to violence has 
been carried out in the United Kingdom under the heading of crime analysis. This begins with a detailed analysis of patterns and circum-stances of crimes and then proceeds to devise, implement, and evaluate crime reduction strategies. For example, it was found that 
most street robberies in London occurred in predominantly ethnic 
minority areas, and most offenders were 16–19 year old Afro-Caribbean males.
(34) The victims were mostly Caucasian females, 
alone, and on foot. Most offences occurred at night, near the victim’s home. The main motive for robbery was to get money, and the main factor in choosing victims was whether they had a wealthy appearance.

In their Montreal longitudinal study of delinquents, LeBlanc and 
Frechette
(35) provided detailed information about motives and 
methods used in different offences at different ages. For example, for violence at age 17, the main motivation was utilitarian or rational. For all crimes, however, the primary motivation changed from 
hedonistic (searching for excitement, with co-offenders) in the teen-age years to utilitarian (with planning, psychological intimidation, and use of instruments such as weapons) in the twenties. In the Cambridge Study, motives for physical ﬁ  ghts depended on whether 
the boy fought alone or with others.
(36) In individual ﬁ  ghts, the 
boy was usually provoked, became angry, and hit out to hurt his opponent and to discharge his own internal feelings of tension. In group ﬁ  ghts, the boy often said that he became involved to help a

boy was usually provoked, became angry, and hit out to hurt his opponent and to discharge his own internal feelings of tension. In group ﬁ  ghts, the boy often said that he became involved to help a 
friend or because he was attacked, and rarely said that he was angry. The group ﬁ  ghts were more serious, occurring in bars or streets, 
and they were more likely to involve weapons, produce injuries, and lead to police intervention. Fights often occurred when minor incidents escalated, because both sides wanted to demonstrate their toughness and masculinity and were unwilling to react in a conciliatory way.
Much is known about the situations in which violence occurs. For 
example, in Sweden, violence preceded by situational arguments typically occurs in streets or restaurants, while violence preceded by 
relationship arguments typically occurs in homes.
(37) In England,

(37) In England, 
stranger assaults typically occur in streets, bars, or discotheques, non-stranger assaults typically occur at home or work, and robberies typically occur in the street or on public transport. Most violence occurs on weekend nights around pubs and clubs, and involves young males who have been drinking.
(38) More research on situa-
tional inﬂ  uences on offending needs to be incorporated in prospec-
tive longitudinal studies, in order to link up the developmental and situational perspectives.

Offending is one element of a larger syndrome of antisocial behaviour that arises in childhood and tends to persist into adult-hood, with numerous different behavioural manifestations. However, while there is continuity over time in antisocial behav-iour, changes are also occurring. It is commonly found that about half of a sample of antisocial children go on to become antisocial teenagers, and about half of antisocial teenagers go on to become antisocial adults. More research is needed on factors that predict these changes over time. Research is especially needed on changing behavioural manifestations and developmental sequences at different ages. More efforts should especially be made to identify factors that protect vulnerable children from developing into antisocial teenagers.

A great deal has been learned in the last 20 years, particularly 
from longitudinal surveys, about risk factors for offending and 
other types of antisocial behaviour. Offenders differ signiﬁ  cantly 
from non-offenders in many respects, including impulsivity, intel-ligence, family background, and socio-economic deprivation. These differences are present before, during, and after criminal careers. While the precise causal chains that link these factors with antiso-cial behaviour, and the ways in which these factors have independ-ent, interactive, or sequential effects, are not known, it is clear that individuals at risk can be identiﬁ  ed with reasonable accuracy. 
In order to advance knowledge about human development and criminal careers, new multiple-cohort longitudinal studies are 
needed.
(39)
The identiﬁ  ed risk factors for offending should be targeted in 
prevention programmes. Risk-focussed prevention has great

1915
potential for crime reduction.(40) The continuity of antisocial 
behaviour from childhood to adulthood suggests that prevention efforts should be implemented early in life. Because of the link between offending and numerous other social problems, any meas-ure that succeeds in reducing offending will have beneﬁ  ts that go 
far beyond this. Any measure that reduces offending will probably also reduce alcohol abuse, drunk driving, drug abuse, sexual pro-miscuity, family violence, truancy, school failure, unemployment, marital disharmony, and divorce. It is clear that problem children tend to grow up into problem adults, and that problem adults tend to produce more problem children. Continued efforts are urgently needed to advance knowledge about offending and antisocial behaviour, and to tackle the roots of crime.
For extensive reviews of risk factors and interventions, see Saving Children

For extensive reviews of risk factors and interventions, see Saving Children 
from a Life of Crime: Early Risk Factors and Effective Interventions  by D. 
P . Farrington and B. C. Welsh (Oxford University Press, 2007). 
For extensive information about the Cambridge Study, see Criminal Careers 
up to Age 50 and Life Success up to Age 48: New Findings from the 
Cambridge Study in Delinquent Development  by D. P . Farrington and 
colleagues (Home Ofﬁ  ce Research Study No. 299), available from 
www.homeofﬁ  ce,gov.uk/rds. 
For other reviews of psychosocial causes of offending, see Antisocial 
Behaviour by Young People , by M. Rutter, H. Giller, and A. Hagell 
(Cambridge University Press, 1998).
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 2. Farrington, D.P ., Coid, J.W., Harnett, L.M., et al. (2006). Criminal

 2. Farrington, D.P ., Coid, J.W., Harnett, L.M., et al. (2006). Criminal 
careers up to age 50 and life success up to age 48: new ﬁ  ndings from the 
Cambridge Study in Delinquent Development . Home Ofﬁ  ce, London 
(Research Study No. 299).
 3. Loeber, R., Farrington, D.P ., Stouthamer-Loeber, M., et al. (1998). 
The development of male offending: key ﬁ  ndings from the ﬁ  rst decade 
of the Pittsburgh Y outh Study. Studies on Crime and Crime Prevention ,
7, 141–71.
 4. Piquero, A.R., Farrington, D.P ., and Blumstein, A. (2007). Key issues 
in criminal career research: new analyses of the Cambridge Study in Delinquent Development . Cambridge University Press, Cambridge.
 5. Farrington, D.P . and Welsh, B.C. (2007). Saving children from a life of 
crime: early risk factors and effective interventions . Oxford University 
 6. Klinteberg, B.A., Andersson, T., Magnusson, D., et al. (1993).

 6. Klinteberg, B.A., Andersson, T., Magnusson, D., et al. (1993). 
Hyperactive behaviour in childhood as related to subsequent alcohol problems and violent offending: a longitudinal study of male subjects Individual Differences ,15, 381–8.
 7. Stattin, H. and Klackenberg-Larsson, I. (1993). Early language and 
intelligence development and their relationship to future criminal behaviour. Journal of Abnormal Psychology ,102, 369–78.
 8. Schweinhart, L.J., Barnes, H.V ., and Weikart, D.P . (1993). Signiﬁ  cant 
beneﬁ  ts: the High/Scope Perry preschool study through age 27 .
High/Scope, Ypsilanti, Michigan.
 9. McCord, J. (1979). Some child-rearing antecedents of criminal 
behaviour in adult men. Journal of Personality and Social Psychology ,
37, 1477–86.
10. Newson, J. and Newson, E. (1989). The extent of parental physical 
punishment in the UK . Approach, London.

11. Morash, M. and Rucker, L. (1989). An exploratory study of the 
connection of mother’s age at childbearing to her children’s delinquency in four data sets. Crime and Delinquency ,35,
45–93.
12. Kolvin, I., Miller, F.J.W., Scott, D.M., et al. (1990). Continuities of 
deprivation? The Newcastle 1000 family study . Avebury, Aldershot.
13. Maxﬁ  eld, M.G. and Widom, C.S. (1996). The cycle of violence 
revisited 6 years later. Archives of Paediatrics and Adolescent Medicine ,
150, 390–5.
14. Smith, C.A. and Thornberry, T.P . (1995). The relationship between 
childhood maltreatment and adolescent involvement in delinquency. 
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15. Brezina, T. (1998). Maltreatment and delinquency: the question of 
intervening processes. Journal of Research in Crime and Delinquency ,

35, 71–99.
16. Henry, B., Caspi, A., Mofﬁ  tt, T.E., et al. (1996). T emperamental and 
familial predictors of violent and non-violent criminal convictions: age 
3 to age 18. Developmental Psychology ,32, 614–23.
17. Wadsworth, M.E.J. (1979). Roots of delinquency: infancy, adolescence 
and crime . Martin Robertson, London.
18. Wells, L.E. and Rankin, J.H. (1991). Families and delinquency: a 
meta-analysis of the impact of broken homes. Social Problems ,
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disrupted families and delinquency. British Journal of Criminology ,
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41, 22–40.
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Disciplines ,16, 125–40.
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of risk factors in the development of delinquency. In Historical 
and geographical inﬂ  uences on psychopathology  (eds. P . Cohen, C. 
Slomkowski, and L.N. Robins), pp. 299–329. Lawrence Erlbaum, Mahwah, NJ.
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delinquency. Deviant Behaviour ,15, 45–61.
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delinquency . Sage, Beverly Hills, California.
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school leaving, and crime. British Journal of Criminology ,26,
335–56.

335–56.
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predictors of youth violence. In Serious and violent juvenile offenders: 
risk factors and successful interventions  (eds. R. Loeber and D.P . 
Farrington), pp. 106–46. Sage, Thousand Oaks, California.
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causes of delinquency the same as between-individual causes? Criminal 
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schools? New Society ,10, 542–3.

29. Rutter, M., Maughan, B., Mortimore, P ., Ouston, J., and Smith, A. 
(1979). Fifteen thousand hours: secondary schools and their effects on 
children . Open Books, London.
30. Shaw, C.R. and McKay, H.D. (1969). Juvenile delinquency and urban 
areas  (rev. edn). University of Chicago Press, Chicago.
31. Sampson, R.J., Raudenbush, S.W., and Earls, F. (1997). Neighbourhoods 
and violent crime: a multilevel study of collective efﬁ  cacy. Science ,
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Contents
disorder and offending
 11.3.2 Offending, substance misuse, and mental disorder
 11.3.3 Cognitive disorders, epilepsy, ADHD, and offending
11.3.1 Associations between 
psychiatric disorder and offending
The associations between psychiatric disorder and offending are

The associations between psychiatric disorder and offending are 
complex. There has been a great deal of research into certain disor-ders and violent offending particularly over the last two decades. In summary, this has found a clear and consistent association between schizophreniform psychoses and violence, the importance of pre-morbid antisocial behaviour in predicting future violence, and the adjunctive effect of co-morbid substance misuse and antisocial personality disorder in the prevalence of violence. In addition, it has allowed the development of neuropsychiatric models to begin to explain violence in the context of mental disorder. Substance use disorders and learning disability are discussed in Chapters 11.3.2 and 11.3.3.
Mental disorder and offending: a 
problematic relationship
Criminal behaviour is common in our society but there is evidence

Criminal behaviour is common in our society but there is evidence 
that violent crime rates have declined in Europe and North America over the last decade.
(1) Mental disorders are also common. It is 
important to study the overlap between mental disorder and offending to consider those mental health and criminogenic factors 
that may be amenable to change. The social and economic factors relevant to offending are discussed in Chapter 11.2.
Before considering any associations between mental disorder 
and offending it is useful to consider the methodological problems in studying these:
◆ Offences are man-made concepts and not static. For example, 
many jurisdictions have created laws against stalking in the last twenty years which did not previously exist.
◆ Psychiatrists see a limited range of offenders but often base their 
research on these.
◆ Research is generally carried out on a captive population in pris-

on or secure hospital. Offenders in these settings are likely to include those with characteristics that disadvantage them in the criminal justice system, for example ethnic status, low economic status, homelessness, unemployment, and mental illness.
◆ The generalizability of any ﬁ  ndings must be queried given that 
offending is dependent on the wider social context such as rates 
of unemployment or crime, prevalence of substance misuse, and weapon carrying culture.
◆ It can be difﬁ  cult to standardize populations studied, and severity 
of crimes.
◆ Criminal and mental health records may be unreliable.
Evidence for neurobiological determinants 
of offending or aggressive behaviour
There is resistance to any oversimpliﬁ  ed idea of seeking a genetic or

There is resistance to any oversimpliﬁ  ed idea of seeking a genetic or 
neuropsychological explanation to offending behaviour as a whole but research in this area is expanding slowly. Neuropsychological abnormalities are commonly found in offenders and there is evidence for specific brain deficits in aggressive or violent behaviour.
(2) These ﬁ  ndings include:
◆ An association between speciﬁ  c traumatic damage to the frontal 
lobes, particularly orbitofrontal injury, and poor impulse control and aggressive outbursts.
◆ Abnormalities on neuropsychological tests of frontal lobe func-
tion in aggressive and antisocial subjects, indicating prefrontal executive dysfunction.Associations between 
psychiatric disorder and offending11.3

SECTION 11  forensic psychiatry 1918
◆ Abnormalities found in clinical neurological testing of offenders. 
Antisocial behaviour is associated with EEG abnormalities particularly frontal slowing and these are commonly found in more than half of prisoners with a history of repetitive violence. Clinical signs of frontal lobe dysfunction are also associated with recurrent aggression.
◆ Neuroimaging changes. Structural and functional studies 
examining patients in forensic services and patients with antiso-cial personality disorder have consistently found changes in the frontal lobes of aggressive patients, typically reduced prefrontal cortical size and activity. Predatory rather than impulsive, emotionally charged (affective) perpetrators of homicide show functional patterns of blood ﬂ  ow similar to controls suggesting

that these neuroimaging findings are relevant to impulsive or affective aggression rather than premeditated, purposeful violence. Two groups of people with aggressive behaviour are postulated: the ﬁ  rst with an acquired frontal lobe lesion due to 
injury or disease which impairs social judgement, risk avoidance, and empathy; the second, shows increased aggressive behaviour 
associated with deﬁ  cits in executive functioning correlating with 
dorsolateral prefrontal dysfunction which may occur in foetal or birth brain injury, developmental learning disorders, attention deﬁ cit hyperactivity disorder, substance misuse, and antisocial 
personality disorder with episodic aggressive dyscontrol.
◆ In addition, there is evidence for biochemical abnormalities. 
Reduced serotonin function is largely related to impulsivity rather than directly to violence.
(3) Serotonin has a role in emo-

tional states such as impulsiveness, aggression, anxiety, and depression. This has provided potential avenues for treatment with selective serotonin reuptake inhibitor medication.
(4)
Cortisol abnormalities have been recognized for a long time and more recently dietary insufﬁ  ciencies have been explored.
(5)
◆ Lastly, the role of genetics in offending behaviour has been exam-
ined through family, twin, and adoption studies.(6) Adoption

(5)
ined through family, twin, and adoption studies.(6) Adoption 
studies have found a consistent association between biological parents and adoptee for property offences but a more complex association for violent crime with a relationship discovered in the Danish birth cohort study between paternal violence and adoptee schizophrenia. A link between a genotype and disturbed behaviour was found in maltreated male children. Those with the gene encoding the neurotransmitter metabolizing enzyme monoamine oxidase A (MAOA) moderated the effect of mal-treatment and had reduced antisocial behaviour in later life.
(7)
MAOA genes have a known association with aggression in ani-mals and humans. The low expression variant leads to increased aggression, limbic volume reductions and hyper-responsive amygdala during emotional arousal with decreased reactivity of regulatory prefrontal regions.
(8) Twin studies have shown

(8) Twin studies have shown 
that antisocial behaviour in early childhood particularly when associated with callous unemotional traits has a strong genetic influence which weakens in antisocial behaviour displayed initially in adolescence when environmental influences are important.
(9)
Such changes are not a necessarily a cause for aggressive behav-
iour which is dependent on so many environmental factors, nor do they necessarily predict aggressive behaviour but they are important to study in that they indicate potential management strategies.Clinical implications of the relationship 
between mental disorder and offending
The nature of the relationship between psychiatric disorder and 
offending is complex both at an individual and population level, and has important implications at both. Epidemiological data point to the following conclusions:
◆Schizophrenia, personality disorder, and substance related disor-ders are signiﬁ  cantly overrepresented in offenders.

◆A number of factors associated with violence and offending in 
the non-mentally disordered are relevant to violence and offend-ing in the mentally disordered.
◆Amongst offenders there is the need to provide psychiatric assessment and treatment for signiﬁ  cant numbers of people with 
mental disorder.
◆Amongst mentally disordered offenders it is important to address criminogenic factors as well as providing traditional clinical treatment
◆Appropriate treatment and preventative measures may prevent some offending and violence by individuals with mental disorders
It is important to know and understand the epidemiological

It is important to know and understand the epidemiological 
research, but also to know and understand the patient that is being assessed. Not all factors of relevance to offending in people with mental disorders act in the same way in every case, and some fac-tors not found to be of relevance in study samples may be crucial in individual cases. There is no simple or straightforward approach to such an assessment, and narrowing one’s focus to a tick list of a few factors (perhaps from an actuarial tool) is at best lazy and at worst negligent. The psychiatrist should be able to articulate a for-mulation incorporating the factors which account for previous offending and which may be of relevance to future offending.
Every violent act involves a perpetrator, a victim, and a context,

Every violent act involves a perpetrator, a victim, and a context, 
and this is no different where mental disorder is involved. A number of factors in the perpetrator, victim, and context in any violent incident are relevant to that violent act, and these three interact with each other. A simple example is that a drunk aggressive victim may frighten a suspicious impulsive perpetrator in the context of alcohol intoxication and an available knife. Where a person with mental disorder is violent one should not assume the 
former straightforwardly causes the latter. Sometimes mental 
disorder is the major determinant of an offence and at others mental disorder is entirely coincidental. In most cases mental disorder is one of a number of interacting factors (Fig. 11.3.1.1). Even where an offence seems explicable by psychotic hallucinations or delusions it is essential to consider wider factors (e.g. alcohol and substance misuse, social networks and personality).
(10)

(10)
A thorough assessment of these factors is crucial when evaluating criminal responsibility (see Chapter 11.1), assessing risk of future offending (see Chapter 11.15) and planning treatment for patients who have been violent. Treating mental disorder without address-ing these factors will not adequately address the risk of further offending.
Scizophrenia and offending
For over a decade, studies have consistently shown a small but sig-niﬁ cant association between schizophrenia and violence with an

1919
increased risk of violence of between 2–4 for men and 6–8 for 
women after controlling for marital status, socio-economic back-ground and substance abuse.
(11) The proportion of violent crimes 
in the population of Northern European countries attributable 
to individuals with severe mental illness is around 5 per cent.(12)
A systematic review of mental disorder in 23, 000 prisoners found 
psychoses in 3.7 per cent of men and 4 per cent of women which was 2–4 times more than in the general population. Aggression in ﬁ rst episode psychosis occurs consistently in one-third of cases.
(13)
Two patterns of aggression associated with schizophrenia are 
seen: ﬁ  rstly, those in whom features of conduct disorder (20-40 per 
cent) and later antisocial personality disorder predate the onset of overt schizophrenia; and secondly, those in whom violence occurs at a later stage.
(11) Psychotic symptoms and violence in childhood

(11) Psychotic symptoms and violence in childhood 
are strongly related to later violence, as is a history of conduct disorder.
(14)
Studies of people convicted of homicide have consistently shown 
an excess of schizophrenia with rates of 5–15 per cent.(15,16) Family 
members are signiﬁ  cantly more likely to be the victim than stran-
gers. Those with comorbid antisocial personality disorder are less likely to be actively psychotic at the time of the offence, and more likely to be intoxicated and to kill non-relatives.
Neurobiological correlates of schizophrenia and 
violence
Naudts and Hodgins(17) examined neurobiological correlates of 
schizophrenia and violence. The literature is small, as are the sample sizes, and the measures used are diverse. At least one-ﬁ  fth of 
men with schizophrenia show antisocial behaviour from childhood onwards. Overall, these men perform better on tests of speciﬁ  c

men with schizophrenia show antisocial behaviour from childhood onwards. Overall, these men perform better on tests of speciﬁ  c 
executive functions and verbal skills despite greater impulsivity; and worse on tests of orbitofrontal functions than men with schiz-ophrenia alone. Structural brain imaging studies of men with schizophrenia and a history of repetitive violence found reduced whole brain and hippocampal volumes; impaired connectivity between the orbitofrontal cortex and the amygdala; and structural abnormalities of the amygdala. Functional neuroimaging studies found reduced prefrontal cerebral blood ﬂ  ow during completion 
of a test of executive function in violent patients. This reduction 
in blood ﬂ  ow may result in loss of inhibition and therefore aggres-
sion, or it may reﬂ  ect that these violent men found the test easier 
and did not need increased blood ﬂ  ow to complete it. Studies

and did not need increased blood ﬂ  ow to complete it. Studies 
of acquired brain lesions show that ventromedial orbitofrontal cortex is necessary for inhibiting impulsive decision-making and behaviour and for physiological anticipation of secondary 
inducers such as punishment. Studies at different ages suggest that an intact amygdala in early life is necessary for the normal development of this orbitofrontal system to recognize and process emotions. This ﬁ  ts with the work of Silver et al.
(18) who found that 
patients with schizophrenia with a history of severe violence differ from non-violent patients with schizophrenia in their perception of the intensity of emotions but not cognitive function. Failure to assess the intensity of emotions may contribute to conﬂ  ict 
generation, failure to recognize resolution signals, conﬂ  ict escalation, 
and violence.

People with schizophrenia may be violent because of their psychotic experiences, impaired judgment and impulse control, or situational factors. The evidence of the effect of symptoms is conﬂ  icting how-
ever, probably because of the way questions are asked; failure to take account of affective symptoms; variation in the timing between symptoms and violence; failure to control for medication, compul-sion and previous violence; and variations in statistical proce-dures.
(19) Swanson et al .(20) in a study of 1 410 people with

(19) Swanson et al .(20) in a study of 1 410 people with 
schizophrenia in a six month period found 19.1 per cent had been violent and this was serious in 3.6 per cent of cases. Positive symp-toms increased the risk of minor and serious violence whereas nega-tive symptoms decreased the risk of serious violence perhaps because these individuals lived alone. Serious violence was associat-ed with psychotic and depressive symptoms, childhood conduct problems, and victimization. Severe psychotic symptoms and threat-control override (TCO) were antecedents of violent behaviour of patients in the community even after controlling for psychopathy and substance abuse.
(21) TCO consists of persecutory delusions, 
passivity phenomena and thought insertion, resulting in perceived personal threat combined with loss of self control. Excessive percep-tions of threat explained violence in people with schizophrenia-spectrum disorder alongside a history of conduct disorder.
(22)

(22)
Hallucinations, acute suicidal ideation, acute conflict and 
stressors such as separations or housing problems, and lack of insight have all been associated with an increased risk of violence.
(23)
Co-morbidity
The likelihood of violence in patients with schizophrenia increases in the presence of comorbid substance use (3-fold in men, 16-fold in women) or personality disorder (4-fold men, 18-fold women).
(11)
Swanson et al.(20) found however, that the effects of substance abuse 
were non signiﬁ  cant after controlling for age, positive symptoms of 
schizophrenia, childhood conduct problems and recent victimiza-
tion thereby suggesting that the effects of substance abuse on vio-lence may be mediated by these factors. There is a strong associa-tion between comorbid antisocial personality disorder and substance abuse in patients with schizophrenia with common origins in conduct disorder.
(24) Further evidence for this is found

(24) Further evidence for this is found 
in neuropsychological tests. Patients with comorbid schizophrenia and substance abuse perform as well as those with schizophrenia alone on neurological tests although it is known that the brains of men with schizophrenia are particularly sensitive to effects of drugs and alcohol. It has been suggested that these men belong to the antisocial group who do better on these tests at the onset of their schizophrenia.
(17)Fig. 11.3.1.1 A schematic representation of the complex interplay between 
factors of relevance to offending in people with mental disorder.SOCIAL DEPRIVATION
POOR PARENTING
LOW INTELLIGENCE
PEER GROUPGENETIC FACTORSSUBSTANCE MISUSEVICTIMIZATIONPERSONALITY
OFFENDINGMENTAL DISORDER11.3.1  associations between psychiatric disorder and offending

SECTION 11  forensic psychiatry 1920
The care of patients with schizophrenia and a history of serious 
violence is centred around ongoing assessment and management of factors contributing to risk of violence and treatment of the schizophrenic illness. Predictors of violence include recent assault, a previous violent conviction, lower educational attainment and attending special education, a personal and family history of alco-hol abuse, and lower but normal range IQ.
(25,26) The management 
of schizophrenia is discussed in Chapter 4.3.8 but in patients with a history of violence methods of legal compulsion for detention and treatment, and programmes to address comorbid and crimi-nogenic needs are particularly important. There is evidence that cognitive behavioural therapy can modify delusional beliefs that have lead to violence
(27) and that clozapine has a particular role in

(27) and that clozapine has a particular role in 
the treatment of aggression in patients with schizophrenia separate from its antipsychotic or sedative components.
(28)
Outcome
There is no indication that deinstitutionalization has lead to increased offending by patients with schizophrenia. Rates of violence have increased but in proportion to the increase in society as a whole and with increased comorbid alcohol abuse.
(29)Outcome 
studies of patients transferred from high security found a recidi-vism rate of 34 per cent and 31 per cent in England and Scotland respectively, and a violent recidivism rate of 15 per cent and 19 per cent after ten years.
(30, 31)  Patients with a primary diagnosis of 
schizophrenia during a follow up period of 8 years had a recidivism rate of 15 per cent and a violent recidivism rate of 5 per cent.
Delusional disorders

Delusional disorders are described in Chapter 4.4. There are a number of subtypes including somatic, grandiose, mixed and unspeciﬁ  ed but it is particularly the jealous, erotomanic and perse-
cutory forms that are associated with offending and violence. Individuals with delusional disorders remain organized allowing them to target and plan any violence more effectively. Sixty percent of people with delusional jealousy are violent towards their partners. In erotomania the patient has the delusional belief that s/he is loved from afar by another and may attack individuals perceived as standing between them and their loved one, or the object of their affections if they feel slighted. Erotomania is associ-ated with anger, harassment, stalking, and violence.
(32)
Delusional disorders are found in excess in homicide (6-fold

(32)
Delusional disorders are found in excess in homicide (6-fold 
increase) and are associated with stalking. Stalking is persistent har-assment in which a person repeatedly intrudes on another in an unwelcome manner that evokes fear or disquiet. One study of stalk-ers found that 30 per cent had a delusional disorder, 10 per cent schizophrenia, less than 5 per cent bipolar disorder or anxiety; 50 per cent had a personality disorder and 25 per cent abused sub-stances. The classiﬁ  cation of stalkers is based on their motivation. It 
is the rejected stalkers who pursue ex-intimates for reconciliation, revenge or both (includes delusional jealousy); intimacy seekers (includes erotomania); and the resentful stalker who pursue victims as revenge for an actual or perceived injury (includes persecutory) who are most likely to have a delusional disorder. This is not the case for incompetent suitors or predatory stalkers. See Chapter 11.10

Risk of harm to others can be reduced by treating the individual’s 
delusional disorder with medication; controlling his or her environment by use of hospital or legal orders to restrict move-
ment; and by advice to any potential victim on protective measures. There have been no randomized controlled trials of the treatment of delusional disorders but novel antipsychotics are now most commonly used due to their lower side-effect proﬁ  le and better 
compliance, and it is recognized that pimozide has no particular role in the treatment of delusional disorder.
(33) Cognitive behavioural 
therapy may assist compliance and insight but this has not been systematically demonstrated. Eye movement desensitization and reprocessing (EMDR) interwoven with cognitive therapy has been reported as a treatment of morbid jealousy. It is essential to warn any identiﬁ  ed potential victims and such a breach of conﬁ  dentiality 
is permitted by medical governing bodies.
Organic disorders

Organic disorders may be related to offending directly because of the brain injury with disinhibition and impaired judgement, or secondarily to socio-economic deprivation and exclusion.
Traumatic brain injury (TBI)
There is a 4-fold increase in the relative risk of developing any psychiatric illness in the six months post moderate to severe TBI and almost 3-fold in mild TBI excluding those with a history of mental illness. Common psychiatric sequelae of traumatic brain injury include mood (50 per cent), anxiety (25 per cent) and substance use disorders (28 per cent) along with post traumatic stress disorder and post traumatic brain injury attention deﬁ  cit 
hyperactivity disorder in children, in addition to any cognitive problems.
(34)
Posttraumatic irritability occurs in up to 70 per cent of people

(34)
Posttraumatic irritability occurs in up to 70 per cent of people 
with TBI. Aggressive behaviour occurs in approximately one-quarter and this is signiﬁ  cantly increased by the presence of major 
depression or substance abuse. Psychological tests of executive function and neuroimaging suggest that defective pre-frontal modulation of medial limbic structures may explain aggressive and impulsive behaviour seen in these patients. TBI patients who display aggression are characterized by signiﬁ  cantly more impul-
sivity, disinhibition and social withdrawal; and poorer drive and motivation.
(35) A study of sex offenders found that half had a his-
tory of head injury leading to loss of consciousness with signiﬁ  cant 
neurological impairment in a quarter.(36) The head injury group

neurological impairment in a quarter.(36) The head injury group 
offended more against adults than children, had more exhibiting and wide ranging sexual behaviours, and abused more substances than their non TBI sex offender controls.
Epilepsy
Contrary to previous views, the evidence now suggests that there is no association between epilepsy and criminal behaviour. A system-atic review of epilepsy in prisoners found a prevalence rate of about 1 per cent which is comparable with a community sample of a similar age and gender.
(37) Epilepsy is considered in detail in 
Chapter 11.3.3.
Dementia
A diagnosis of dementia and being charged with a sexual offence were factors most likely to distinguish those over 60 years of age referred by courts for a psychiatric assessment in Sweden compared to their younger counterparts although all forms of psychoses

1921
(31 per cent), personality disorder (20 per cent), and substance use 
disorders (14.8 per cent) were more frequently diagnosed than dementia (7 per cent).
(38) Offending is much less common in the 
elderly. Physical aggression in dementia however, is not uncommon and may be associated with exposure of intellectual deﬁ  cits during 
testing (catastrophic reaction), severe cognitive impairment, impaired expression and comprehension, a history of premorbid aggression, physical illness particularly involving delirium or pain, post ictal confusion, depression and changes within the environment. Frontotemporal or orbitotemporal degeneration are more frequently associated with aggression in dementia, as are reduced serotonin and acetylcholine.
(39)
Autism spectrum disorders

(39)
Autism spectrum disorders (ASD) (including autism and Asperger’s syndrome) are described in Chapter 9.2.3. In the severe form (autism) incapacity is frequently major and affected individuals are consequently unlikely to come into contact with the judicial system. The frequency of the lesser forms is inadequately researched. Although the majority of individuals with ASD are law abiding—and many indeed may be less likely to offend as a result of ‘concrete’ rule-based thinking—they are found in excess in high security psychiatric settings. Those who offend may do so because of feelings of resentment caused by bullying or rejection at school or in the community, because of an over-sensitivity to sound, occa-sionally because of a powerful interest in guns, ﬁ  re or killing
(40)
or because of a lack of appreciation of social norms. Theft may 
occur in order to pursue a particular interest or obsession.

(40)
The link between personality disorder and offending and the role of psychiatry in managing personality disordered offenders is com-plicated by a number of issues: poor diagnostic systems; variable and subjective approaches to assessment; confusing legislative approaches seeking to deﬁ  ne and impose measures on certain

individuals; societal preoccupation with ‘psychopaths’ and ‘sexual predators’; and uncertainty as to what treatment, if any, is effective. The concept of anti-social personality disorder, introduced in DSM-III and rehashed in DSM-IIIR and DSM-IV , has been unhelpful. Its reliance on socially deviant behaviour, rather than personality traits, reliably demarcates a broad heterogeneous group with varying underlying psychopathology and social problems. Personality disorder should not be diagnosed primarily on the basis of repeated anti-social behaviour. Assessment of personality 
in offenders should be based on pervasive and persistent emotional

in offenders should be based on pervasive and persistent emotional 
experience and expression, thoughts about self and others, interac-tions with others and behavioural control. Personality disordered offenders show a range of personality pathology rarely falling neatly into the diagnostic boxes of ICD 10 or DSM-IV . Focussing on personality disorder as a clinical entity misses relevant develop-ments in assessment and management of such individuals from research and practice in criminal justice.
Psychopathy
The term psychopathy has a long and chequered history (see Chapter 4.12.1). Its clinical use should probably be reserved for individuals fulﬁ  lling Hare’s criteria
(41) (based on Cleckley’s ‘Mask 
of Sanity’(42) describing superﬁ  cial, self-centred, callous, parasitic, impulsive, aggressive, predatory individuals. Hare operationalized 
psychopathy with the Psychopathy Check List-Revised (PCL-R). Interview and case ﬁ  le material is used to assess 20 items on a

psychopathy with the Psychopathy Check List-Revised (PCL-R). Interview and case ﬁ  le material is used to assess 20 items on a 
3-point scale giving a maximum total score of 40. In North America a cut-off of 30 is used to diagnose psychopathy. In Europe the cut-off may be lower, but this is a contentious area. The total score 
may be useful for research purposes, but the proﬁ  le of characteris-
tics is important in clinical assessment and formulation. Underlying the construct are emotional, interpersonal and behavioural domains. Hare originally described two underlying factors: Factor 1 (emotional and interpersonal) correlated with narcissistic and histrionic disorders, and Factor 2 (socially deviant life style and behaviour) correlated with anti-social and borderline disorders. This has been reﬁ  ned into a four factor model subdividing factor

1 into interpersonal and affective domains, and factor 2 into life-style and antisocial behaviour domains. It has been suggested that the antisocial behaviour domain is not core to the condition.
(43)
Psychopathy is a narrower construct than dissocial (ICD 10) or antisocial (DSM-IV) personality disorder, so research ﬁ  ndings 
cannot be extrapolated. It is an important concept in theory, research and practice concerning offender management and recidivism. But psychopathy only focuses on a limited, albeit important, set of personality traits of relevance in assessing offenders. Comprehensive consideration of personality pathology involves broader assessment. Patrick’s book
(44) gives an authorita-
tive account of psychopathy.
Relationship between personality disorder and 
offending
Personality disorder rates in prisoners range from 10 per cent(45) to 
78 per cent(46) depending on study method. Lower rates are found

offending
78 per cent(46) depending on study method. Lower rates are found 
with comprehensive clinical assessment, higher rates with struc-tured tools administered by non-clinicians. In male prisoners the most prevalent disorder category is, unsurprisingly, antisocial followed by paranoid, then borderline, then obsessive compulsive, avoidant and narcissistic at similar rates.
(46) In Fazel and Danesh’s 
systematic review(37) 65 per cent of male prisoners were personality 
disordered (47 per cent anti-social); amongst female prisoners the rate was 42 per cent (25 per cent borderline, 21 per cent anti-social). Psychopathy has been found in 10 to 30 per cent of prisoners.
(47)
Blackburn and Coid highlighted the heterogeneity of personality 
pathology in violent offenders.(48) Using cluster analysis they found

(47)
pathology in violent offenders.(48) Using cluster analysis they found 
six diagnostic patterns: antisocial-narcissistic, antisocial-paranoid, borderline-antisocial-passive aggressive, borderline, compulsive-borderline, and schizoid. The three antisocial groups displayed more psychopathy. Half of homicide offenders in Sweden were per-sonality disordered
(49) but the rate in the UK was about 10 per cent(15)
(an underestimate due to the method of the study). Rates of per-sonality disorder are high in sexual offenders.
(50) Adult rapists have 
higher rates of psychopathy than child molesters who have higher rates of avoidant and dependent disorders. Sexual homicide offend-ers have high rates of psychopathy and other personality disorders, particularly in serial offenders and sexual sadists. Sadistic personal-ity disorder (deﬁ  ned in the DSM-IIIR appendix) is found in up to

a quarter of violent and sexual offenders, but is present with other personality pathology and is associated with sexual sadism.
(51)
There is little support for its recognition as a discrete disorder. Most serial arsonists have personality disorders. Borderline, narcissistic and antisocial subtypes of domestically violent men have been 11.3.1  associations between psychiatric disorder and offending

SECTION 11  forensic psychiatry 1922
identiﬁ  ed.(52) Personality disorder of various types is common in 
stalkers.(53) Psychopathy is particularl y associated w ith instrumental
violence, but reactive violence is also displayed.(44)
Population based cross sectional and birth cohort studies show 
offending and violence to be increased in individuals with person-ality disorders, particularly cluster B disorders.
(54,55) Follow-up 
studies show higher rates of offending and violence in personality disordered subjects in general and forensic samples, particularly associated with psychopathy.
(56,57,58) High rates of comorbid per-
sonality disorder are found in offenders with mental illness(59)and
learning disability.(60) A range of personality pathology is found 
amongst patients detained under ‘psychopathic disorder’ and ‘men-tal illness’ legal categories in English secure hospitals.
(59) Most legal 
‘psychopathic disorder’ patients are not psychopaths.(61)

Various traits, individually and combined, are relevant to 
offending. Some lead to interpersonal conﬂ  ict (suspiciousness, 
hostility, argumentativeness, rigidity, arrogance, clinginess), others to behavioural dyscontrol, others to angry emotional reactions, others to not considering consequences for self or others, others to taking pleasure in violating rules and others. Personality pathology may lead to inability to form intimate relationships, maintain work, establish a stable lifestyle or meet basic needs, which may predis-pose to offending. Impulsivity, need for stimulation, intolerance of dysphoric affect and inability to regulate affect predispose to drug and alcohol misuse leading to offending (see Chapter 11.7).

Assessment, as in other cases, involves a comprehensive history, current mental state examination, and information from records and informants. Structured approaches to personality assessment (e.g. PCL-R and International Personality Disorders Examination (IPDE)), may be incorporated but ‘psychometrics’ should not be used in isolation. Comorbid mental illness should be considered and structured approaches to risk assessment should be used, especially with serious violent or sexual offenders. A comprehen-sive formulation should consider the relationship between dys-functional personality traits and offending.
Discussion of treatment is easily hijacked by the political agenda (largely focussed on protecting the public from dangerous psycho-paths), the criminal justice context and legal issues. Although it would be naïve to consider treatment in isolation from these other issues, clinical management should be the starting point and primary concern of psychiatrists.

Most personality disordered offenders are not serious offenders, 
and their treatment needs are similar to individuals with personal-ity disorder generally (see Chapter 4.12.7). General (e.g. long-term support and attention to relationships) and speciﬁ  c (e.g. psycho-
logical therapies and medication) approaches are relevant to many offenders. The application of such approaches within the criminal justice system or secure hospitals is complicated by coercion, the legal context and institutional factors. How should the success of 
treatment be measured? Amelioration of distress, improved social 
functioning or diminished reoffending? The three may be related, but the public, understandably, expects treatment to prevent offending.
Studies of consenting community patients cannot be extrapo-
lated to serious offenders. The widespread view that psychological treatment programmes increase risk in psychopathic offenders 
is not backed by the literature, with mixed views and empirical

is not backed by the literature, with mixed views and empirical 
ﬁ ndings.
(62) The answer to ‘Is psychopathy treatable?’ is that the 
jury is still out and will be for some time. This does not mean treat-ment is ineffective or inappropriate for the range of personality pathology in serious offenders.
Cognitive behavioural programmes for offending behaviour 
have a moderate positive impact on recidivism.
(63) Many of the

(63) Many of the 
areas targeted in such treatments relate to dysfunctional personality traits and many who go through these programmes have personal-ity disorders. Adaptations for individuals with high levels of personality dysfunction and psychopathy have been made incorpo-rating: greater focus on motivation, engagement, maintaining participation; using more appropriate learning styles; addressing underlying core beliefs; greater ﬂ  exibility; emphasis on individual 
formulation, and positive psychology.
(41) Whether such approaches 
lead to reduced recidivism awaits evaluation.
Although treatment in hospital may seem appropriate if there 
is to be a therapeutic approach, there are descriptions of prisons where a therapeutic environment has been achieved.
(64) Detention 
in hospital primarily for indeﬁ  nite incapacitation of dangerous 
offenders is controversial.

Personality disordered violent and sexual offenders have treat-
ment needs, but they do not ﬁ  t into traditional psychiatric systems, 
geared towards psychotic offenders. The approach with the latter is diversion from criminal justice to health care. With personality disordered offenders, the appropriate approach is probably to pro-vide assessment and treatment within a criminal justice framework, in prison or community. Hospital treatment, as a scarce and expen-sive resource, should be reserved for those who have the potential to engage and benefit. Meux et al  comprehensively describe 
hospital treatment approaches.
(65) Staff working with personality 
disordered offenders, particularly with more severe pathology, need appropriate selection, training, support and supervision. Psychodynamic supervision of staff is important.

Management in the community involves monitoring, supervi-
sion and treatment by various agencies. In the UK Multi-Agency Public Protection Arrangements (MAPPA) are used to co-ordinate the management of violent and sexual offenders in the community. Within this mental health professionals can focus primarily on clinical assessment and treatment whilst criminal justice agencies focus on monitoring and supervision.
Outcome
Certain personality disorders are associated with risk of recidivism. Psychopathy is associated with high rates of general and violent recidivism.
(41) Amongst sex offenders psychopathy predicts violent 
rather than sexual offending, although sexual deviation with psy-chopathy is a malignant combination.
(66) Psychopathy is associated

(66) Psychopathy is associated 
with violence towards victims and diverse offending. Successful social integration following discharge has been found to be associated with not being reconvicted.
(67) Personality disorder is 
associated with suicide in offenders.(68)
An insanity defence, although historically relevant in some juris-dictions, is not usually available where the primary diagnosis is personality disorder. The partial defence of diminished responsi-bility is open to personality disordered homicide perpetrators in

1923
England and Wales. Hospitalization does not often follow such a 
ﬁ nding.
Detention in hospital is rather arbitrarily applied to some per-
sonality disordered offenders in England and Wales. Indeﬁ  nite 
detention in hospital as a sentence can become lifelong incapacita-
tion in a clinical setting.(69) T o ensure that hospital detention is 
treatment focussed there should be prolonged assessment ﬁ  rst. 
Some argue treatment in hospital should only occur via transfer to hospital during a prison sentence. In the Netherlands and Germany, personality disordered offenders are routinely detained in forensic hospitals.
Sexually violent predator laws allow civil commitment (and 
hospital detention) of mentally disordered high risk sex offenders at the end of a prison sentence in some US states.
(70) Most offenders 
are personality disordered and these laws have survived constitu-tional challenge.
In many jurisdictions indeterminate sentences are applied to

In many jurisdictions indeterminate sentences are applied to 
some offenders who are considered to pose an ongoing risk of serious offending.
(71) Many such offenders are personality 
disordered. Psychiatric assessment of risk in such cases is consid-ered unethical by some. Assessments of risk and personality disorder by psychiatrists have been used to under-write the appli-cation of the death penalty in some US States.
(72)
Mood disorders are less related to offending than schizophrenia. Disinhibition and grandiosity in individuals with mania leads to public order offences, driving offences, theft, fraud and minor violent or sexual offences. Serious violent or sexual offending is rare. Treatment non-compliance and comorbid substance misuse are associated with offending.
Depression is not uncommon in prisoners (10 per cent in Fazel 
and Danesh’s systematic review

(37)) but rarely leads to offending. 
The association between depression and shoplifting in the histori-cal literature is probably spurious. When depression is encountered in an offender, it may not have been present prior to the offence. If it was it is unlikely to have played a direct role. High life-time rates of depression are reported in sex offenders, and low mood may be one factor of importance in the path to re-offending in some.
Suicide follows 5 per cent of homicides in the UK.
(73) Depression 
sometimes plays a role but other psychopathology is also seen. Types of offences include:
◆ Spousal: with pathological jealousy.
◆ Spousal: elderly men with poor health and/or ailing spouses who 
feel either or both cannot cope with declining health, adversity, or loneliness.
◆ Filicide-suicide: depressed mother kills her child(ren) and 
herself to save them from a worse fate.

◆ Familicide-suicide: depressed, paranoid, or intoxicated male kills 
the family and himself in the context of ﬁ  nancial, marital, or 
other social stresses.
◆ Extra-familial murder-suicide: disgruntled, paranoid, narcissis-
tic individuals who feel slighted or humiliated, take revenge on single or multiple victims, either as speciﬁ  c targets or as 
bystanders. This pattern is seen in spree killings.Altruistic homicide and extended suicide are terms used where 
a depressed person kills one or more family members to ‘spare them suffering’ and commits or attempts suicide. Most are ﬁ  licide-

suicide and familicide-suicide cases. Depressive psychosis with nihilistic delusions is seen in a minority. It is probably impossible to identify these cases in advance, but it is prudent to explore thoughts about children in parents presenting with suicidal ideation.
Publicity has been given to the association between SSRI 
anti-depressants and aggression and suicide. There is no epidemio-logical data to back these claims, and some evidence SSRIs reduce 
impulsivity and associated aggression.
(74)
Severe depression or mania may make an accused unﬁ  t to plead;

(74)
Severe depression or mania may make an accused unﬁ  t to plead; 
affective psychosis may be accepted as the basis of an insanity defence; and milder forms of mood disorder may found a defence of diminished responsibility in homicide cases. Very few patients in secure hospitals are detained on the basis of mood disorder. In England and Wales, mothers with postpartum disorders who kill their children are usually convicted of infanticide rather than murder.
Neurotic disorders
Neurotic symptoms are common in offenders, but it is unusual to ﬁ nd a close relationship between an offence and an ICD-10 neu-
rotic, stress-related, or somatoform disorder. In many offenders it is possible to identify neurotic conﬂ  icts and ﬁ  nd symbolic meaning 
in criminal behaviour.
(75) Acute stress reactions and adjustment

(75) Acute stress reactions and adjustment 
disorders may be associated with offending, particularly where the underlying personality is abnormal or substance misuse occurs. Social phobia may be relevant through its association with alcohol misuse. Although violent and sexual themes often feature in obsessions, obsessive compulsive disorder is negatively correlated with violence and offending. Obsessional features are sometimes seen in the paraphilic behaviour of some sexual offenders.
Post-traumatic stress disorder (PTSD) may be a contributory 
factor to offending. Offending rarely results directly from ﬂ  ash-
backs or other re-experiencing phenomena, although there are cases where rape victims have attacked sexual partners. PTSD may contribute to the violence of women towards abusive partners. ‘Battered Woman Syndrome’ has been suggested as a sub-category 
of PTSD in such cases.
(76) PTSD rarely leads to a defence of insanity,

(76) PTSD rarely leads to a defence of insanity, 
but may lead to diminished responsibility.
UK psychiatrist read with astonishment and incredulity accounts 
from the US of multiple personality disorder,(77) where the diagno-
sis has justiﬁ  ed separate legal representation for alters, separate 
testimony from alters, unﬁ  tness to plead, the insanity defence, 
and malpractice suits when the diagnosis is ‘missed’ . James and Schramm
(78) give guidance to avoid repetition of the US experi-
ence in the UK. Psychiatrists are advised not to collude by looking for further alters, investigating those that ‘appear’ , and treating the patient as if he were more than one person. Frankel and Dalenberg
(79) give a comprehensive account of dissociation and 
dissociative identity disorder in the US context.
Factitious illness by proxy

Also called Munchausen syndrome by proxy, this is the fabrication of symptoms in, or the injury of, a child by its carer who presents 11.3.1  associations between psychiatric disorder and offending

SECTION 11  forensic psychiatry 1924
the child for medical attention.(80) There is a wide range of injuri-
ous behaviours from fabricating symptoms and tampering with 
specimens and charts to poisoning, smothering, and withholding of nutrients. It is a behaviour rather than a psychiatric disorder. It may feature in systematic and serial child abuse, and in serial killings by health-care workers. Underlying disorders include personality disorders (narcissitic, borderline, and antisocial), somatization, mood, eating and substance misuse disorders. Psychodynamic literature offers various perspectives. In a number of highly publicized cases in the UK, expert evidence regarding families with multiple unexplained child deaths has led to mothers being convicted of murder. Several cases have been overturned on appeal with subsequent disciplinary action against the experts involved.
Impulse control disorders

Impulse control disorders are described in Chapter 4.13.1. Two speciﬁ  c ‘disorders’ have relevance in forensic psychiatry: kleptoma-
nia and pyromania. Psychiatric aspects of arson are described in Chapter 11.9
In clinical practice, it is rare to ﬁ  nd a shoplifter who meets crite-
ria for kleptomania without underlying psychiatric disorder (mood, anxiety or eating disorder).
(81) Apparently inexplicable acts of 
shoplifting may be perpetrated by people who have no features of kleptomania. Goldman
(82) in an extensive review concluded that 
the disorder is more common than previously suggested.
The diagnosis of pyromania is of equally dubious validity. 
Most repeated arson offenders with the clinical features are exclud-ed as they have other underlying disorders (psychosis, intellectual disability, or personality disorder) or are intoxicated when they set ﬁ res.
(83)

(83)
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11.3.2 Offending, substance 
misuse, and mental disorder
This chapter deals with the relationship between offending, sub-
stance misuse, and mental disorder, and also describes approaches to clinical and medico-legal assessment.
Relationship between offending, substance 

The nature of this relationship is complex, yet has to be understood 
in order to manage the health and risk of offending of individual patients. Offences related to substance misuse can be categorized as (i) violent offences, often involving an altered mental state, (ii) acquisitive offences, and (iii) miscellaneous offences such as breaking laws to control the misuse of drugs, driving under the 
inﬂ uence of alcohol, and impact of substance misuse on parenting.
Violent offences
Aggression is not an inevitable pharmacological consequence 
of misusing alcohol or any particular drug, but arises from many possible factors including expectancy effects, pattern of consump-tion, individual responses to intoxication or withdrawal, peer inﬂ  u-
ences, and interpersonal issues.

Alcohol consumption is the single factor most associated with 
violence. It is a repeated ﬁ  nding from the British Crime Surveys 
that alcohol is a key factor in at least half of interpersonal assaults, with a greater contribution to assaults on strangers and domestic violence. By comparison, drug misusers are overwhelmingly more likely to commit acquisitive offences.
The co-morbidity of major mental illness and substance misuse 
further increases the risk of violence. For example, in the Epidemiological Catchment Area (ECA) survey of 10 000 indivi-
duals,
(1) the prevalence of violent behaviour in the previous year 
was 2 per cent for those with no mental disorder, 7 per cent in ‘major mental illness’ , 20 per cent for ‘substance misuse disorder’ , and 22 per cent for co-morbid respondents. Among patients with ﬁ rst-episode psychoses,
(2) just under 10 per cent demonstrated

(2) just under 10 per cent demonstrated 
serious aggression when psychotic and 23 per cent showed lesser degrees of aggression. Those co-morbid for drug misuse were nine times more likely to show aggression after service contact—primary drug-related psychoses or alcohol misuse were not so associated.
There is particular concern in the UK about the risk to the public 
from serious violence by the mentally disordered. Nationally,
(3)
alcohol or drug misuse contributes to two-ﬁ  fths of homicides and 
17 per cent were committed by patients with severe mental illness and substance misuse. Alcohol- and drug-related homicides were generally associated with male perpetrators who had a history of violence, personality disorders, mental health service contact, and with stranger victims.
However, these epidemiological studies cannot deﬁ  ne a causal

However, these epidemiological studies cannot deﬁ  ne a causal 
link between substance misuse and mental disorder. There are many ways in which violence may arise in substance misusers and in co-morbid individuals. Simple intoxication on alcohol or other depressants such as benzodiazepines or barbiturates, leads initially to apparently excited behaviour. Stimulants such as cocaine or amphetamines, may produce arousal and irritability. Most forms 
of intoxication are also associated with impaired judgement, 
perception, and impulse control. Severe intoxication on alcohol, Cannabis, sedatives, or stimulants can lead to a toxic psychosis and highly disturbed behaviour. Even at levels of consumption insufﬁ  -

cient to intoxicate, disinhibition, and autonomic arousal may facilitate recklessness and aggression. Pathological intoxication, in which aggression is supposed to occur within minutes of consum-ing moderate amounts of alcohol, is of doubtful validity and in most cases, better explained by alcohol-induced hypoglycaemia, head injury, or other organic disorder.
The association between withdrawal effects and potential for 
violence is often overlooked. Withdrawal from alcohol and most drugs of dependence, is a highly aversive state in which irritability and aggression may occur. Cessation from alcohol or sedatives, may lead to more severe withdrawal syndromes such as delirium tremens which are commonly associated with impaired perception, affect, judgement, and impulse control.

1927
Acquisitive offending
The relationship between acquisitive crime and drug misuse prob-
lems was studied among 753 clients recruited to the National Treatment Outcome Research Study (NTORS).
(4) More than 17 000 
offences were reported during the 90-day period prior to treat-ment. Half of the clients committed no acquisitive crimes during this period, whereas 10 per cent committed 76 per cent of the crimes.
Such work does not demonstrate a causal relationship between 
illicit drug use and acquisitive crime. From a large survey of British youth,
(5) the average age of onset for truancy and crime are 13.8 and 
14.5 years respectively, compared with 16.2 for drugs generally and 19.9 years for ‘hard’ drugs. Thus, crime tends to precede drug use rather than vice versa. It is clear that heavy drug use is strongly associated with impulsive acquisitive offending, including street robbery, and burglary, which involve violence.
Other offences

In Britain, the non-medical use of drugs is subject to the Misuse of Drugs Act 1971, as subsequently amended, and which contains a classiﬁ  cation based on perceived harm. Class A drugs include 
Ecstasy, LSD, heroin, cocaine, crack, magic mushrooms (if prepared for use), amphetamines (if prepared for injection); Class B drugs include amphetamines and methylphenidate (ritalin); Class C drugs include Cannabis, tranquilizers, some painkillers, Gamma hydroxybutyrate (GHB), ketamine. In January 2004, Cannabis was reclassiﬁ  ed from a Class B to a Class C drug, it is still illegal. This 
legislation deﬁ  nes the penalties for supply, dealing, production, 
trafﬁ cking, and also possession.
Other offences include driving cars, or public conveyances such 
as trains whilst under the inﬂ  uence of alcohol or other drugs.
Responding to the drug or alcohol using 
offender
Clinical- and risk-assessment
The following is a practical guide to assessing the drug or alcohol-

offender
using offender.
1 Obtain a detailed life history, with corroboration from other 
informants and agencies. This should include relationships, work record, and current social situation.
2 Take a detailed history of all of the substances of misuse, includ-
ing onset of regular use, dosage, route of administration, and pattern of use in a typical week. Ask about the desired effects of substance misuse, and also the actual effects. If there is also a serious mental illness, ascertain the effect of substance misuse on symptoms and behaviour. Has previous or recent substance misuse been associated with self-harm or aggression? Note any history of substance misuse treatment and the effects of this.
3 Take a detailed history of previous and recent offending with

3 Take a detailed history of previous and recent offending with 
reference to the effects of substance misuse and mental illness, on mental state and behaviour before, during, and after each offence. Corroborate where possible from witness statements and independent sources.
4 Take a detailed mental state including some assessment of intel-
ligence and personality, and also degree of insight into their offending, illness, and substance misuse.5 Consider with the patient, the practical implications of this 
assessment for immediate clinical management and any need for 
medico-legal reporting that may arise.
There is increasing recognition of the role of actuarial instru-
ments such as the HCR-20 (Historical/Clinical/Risk-management 20-item scale)
(6) which allow for previous and current substance 
misuse to evaluated in the context of other signiﬁ  cant risk factors.
Informed by the above, carry out a risk-assessment, firstly

Informed by the above, carry out a risk-assessment, firstly 
by deﬁ  ning the nature of any risk such as self-harm or relapse 
in substance misuse or of a primary mental illness. If a risk of violence is identiﬁ  ed, this may involve particular individuals such 
as family, partners, or carers. Assess the probability and severity of each risk, and whether there are any early warning signs, such as particular behaviours or symptoms, or non-compliance with treatment.
Risk- and clinical management
Maden(7) (2007) argues ‘the ﬁ  rst step in improving risk-management 
is to recognize that that the prevention of violence is a central task of mental health services’ . As a general approach to risk-management of the drug or alcohol misusing offender, ascertain what risk factors may be changed, and how the provision of support, care, or security may reduce the risk.

It is clearly important to achieve cessation or control of drug or 
alcohol misuse. These are not easy aims, but it is important to dispel therapeutic nihilism and to appreciate that a range of interventions have been shown to be effective. Details of speciﬁ  c interventions 
are given in Chapter 4.2.2.4 and Chapters 4.2.3.1–4.2.3.7.
Treatment can reduce re-offending. The NTORS
(4) found that 
5 years after treatment, convictions for acquisitive, drug selling, and violent crimes had reduced.
The National Conﬁ  dential Inquiry
(8) has concluded that provi-
sion for dual diagnosis should be central to modern mental health care and should include: staff training in substance misuse man-agement, joint working with drug and alcohol teams, local clinical leadership and use of enhanced Care Programme Approach for all those with severe mental illness, and a destabilizing substance misuse problem.
Possible defences related to substance misuse

Generally speaking, the acute effects of having voluntarily taken drugs or alcohol are not a mitigating factor and it is argued that a drunken intent is still an intent. There are however narrowly deﬁ ned circumstances in which an altered mental state due to sub-
stance misuse can raise the question of a possible defence.
(9)
Amnesia
Amnesia is common after violent offending, may relate to acute 
intoxication especially on alcohol or sedatives. In the absence of organic disease, amnesia does not affect ﬁ  tness to plead, though it 
clearly complicates assessment of the perpetrators mental state at the time of an offence.
Simple intoxication
Self-induced intoxication is generally no defence to a criminal charge. However, in England and Wales, case-law has determined 11.3.2  offending, substance misuse, and mental disorder

SECTION 11  forensic psychiatry 1928
that crimes such as murder, wounding with intent, theft, and bur-
glary, require a speciﬁ  c intent , for which self-induced intoxication 
on alcohol or drugs may be a defence, but only if it can be shown that the accused was so intoxicated as to be unable to form the necessary intent. The psychiatrist can only comment as to whether the accused had the capacity to form the speciﬁ  c intent. It is a mat-
ter for the jury to determine whether the speciﬁ  c intent was present 
or not. If the speciﬁ  c intent is not demonstrated, then the accused 
may still be convicted of a lesser offence, so that acquittal on a charge of murder may lead to a conviction for manslaughter. It is a matter of clinical judgement as to whether an individual was so intoxicated as to be unable to form a speciﬁ  c intent, and the degree 
of purposiveness before, during, and after the offence, may be a useful indication.

Other crimes such as manslaughter, rape, and unlawful wounding, 
require only a basic intent , which cannot be negatived by intoxica-
tion. For these offences, the recklessness of voluntary intoxication may provide the necessary mental guilt.
Insanity
Alcohol or drug misuse may give rise to a psychotic illness, such as delirium tremens, which may meet the requirements of the McNaughton rules, but the inanity defence is rarely used. In theory, consumption of drugs or alcohol could lead to a state of insane automatism, but the defence of insanity is not available if the con-sumption has been voluntary.
Diminished responsibility
In England and Wales, Section 2 of the Homicide Act 1957 provides a defence of diminished responsibility in a charge of murder. The defence has to demonstrate that an abnormality of mind  arises from 
one of the causes speciﬁ  ed in the Act and those of possible relevance

one of the causes speciﬁ  ed in the Act and those of possible relevance 
to substance misuse are disease ,injury  or inherent causes . An abnor-
mality of mind due to intoxication is no defence. Alcohol depen-dence could meet criteria for disease , provided that the ﬁ  rst drink of 
the day was shown to be involuntary. Diminished responsibility may become an issue when the effects of substance misuse interact with other factors such as organic brain damage, depression, or per-sonality disorder. For legal purposes, the effect of intoxication has to be set aside and the defence must show that the associated condition was in itself severe enough to lead to an abnormality of mind.
Psychiatric recommendations to the courts

In reporting to the court, the task of the psychiatrist is to explain the possible contribution of substance misuse to a particular offence, in the context of the life history, psychiatric, and offending history of the individual. The aim of such a report is (i) to consider relevant psychiatric issues and their bearing on the offence, (ii) to indicate whether treatment could usefully prevent re-offending, and (iii) to help the court to protect society. There are a range of legal interventions that can facilitate engagement in treatment in community settings.
 1. Swanson, J.W. (1994). Mental disorder, substance abuse, and 
community violence: an epidemiological approach. In Violence and 
mental disorder—developments in risk assessment  (eds. J. Monahan and 
H.J. Steadman), pp. 101–36. University of Chicago Press, London. 2. Milton, J., Amin, S., Singh, S.P ., et al. (2001). Aggressive incidents in

H.J. Steadman), pp. 101–36. University of Chicago Press, London. 2. Milton, J., Amin, S., Singh, S.P ., et al. (2001). Aggressive incidents in 
ﬁ rst-episode psychosis. The British Journal of Psychiatry ,178, 433–40.
 3. Shaw, J., Hunt, I.M., Flynn, S., et al. (2006). The role of alcohol and 
drugs in homicides in England and Wales. Addiction ,101, 1071–2.
 4. Gossop, M., Trakada, K., Stewart, D., et al. (2005). Reductions in 
criminal convictions after addiction treatment: 5-year follow-up. 
Drug and Alcohol Dependence ,79, 295–302.
 5. Pudney, S. (2002). Home ofﬁ  ce research study 253, the road to ruin? 
Sequences of initiation into drug use and offending by young people in Britain. Home Ofﬁ  ce Research, Development and Statistics 
Directorate, UK.
 6. Webster, C.D., Douglas, K.S., Eaves, D. et al. (1997). HCR-20 :assessing 
risk for violence  (version 2). Mental Health Law and Policy Institute, 
Simon Fraser University, Vancouver.

6. Webster, C.D., Douglas, K.S., Eaves, D. et al. (1997). HCR-20 :assessing 
 7. Maden, T. (2007). Treating violence; a guide to risk management in 
mental health . Oxford University Press, Oxford.
 8. Avoidable deaths. Five year report of the National Conﬁ  dential 
Inquiry into suicide and homicide by people with mental illness. (2006). University of Manchester.
 9. Haque, Q. and Cumming, I. (2003). Intoxication and legal defences. 
Advances in Psychiatric Treatment ,9, 144–51.
11.3.3 Cognitive disorders, 
epilepsy, ADHD, and offending
‘Cognitive disorders’ is a broad and heterogeneous diagnostic 
category, which includes different disorders, each with a distinct

category, which includes different disorders, each with a distinct 
aetiology. They affect individuals in different ways depending on the age in which they occur. The term may be applied to a child, who has experienced perinatal trauma as well as to an older person with a beginning dementia of the Alzheimer type. The scientiﬁ  c 
literature on offenders with cognitive disorders is sparse. Most authors in forensic psychiatry do not systematically differentiate between the diagnostic subcategories and tend to use broad terms, such as organic disorder, organic psychosis, organic brain syndrome, neuropsychological deﬁ  cit, dementia, mental handicap, mental

retardation to include a number of different disorders in their studies. The number of patients with any kind of brain disorder in forensic hospitals and institutions is comparatively small and ranges from 1 to 10 per cent of all forensic inpatients. The same numbers apply for individuals assessed for criminal responsibility or risk of reoffending.
(1–3) Compared to major mental disorders 
like schizophrenia or affective disorders or to personality disorders, patients with cognitive disorders account for only a small propor-tion of individuals seen by forensic psychiatrists. Subdividing this group any further would be statistically irrelevant. The way forensic psychiatry and the law deals with offenders suffering from organic brain disorders is rather derived from case reports and convention than from empirical knowledge.
DSM-IV-TR cites several disorders where aggression is either a 
diagnostic or associated feature and among them are four with an organic aetiology.

◆ Dementia of the Alzheimer type (DAT)
◆ Dementia caused by head trauma

1929
◆ Personality change due to general medical condition (aggressive 
type)
◆ Postconcussional disorder
The psychiatric and general medical literature lists several other 
organic brain disorders that are either believed to be or in fact are associated with violence and offending, although their link is not as well proven.
(4)
◆ Epilepsy
◆ Huntington’s chorea
◆ Korsakow psychosis
◆ Brain tumours
◆ Mental retardation
From the experience of the author two other disorders should be 
added to this list:
◆ Traumatic brain injury
◆ Frontotemporal dementia
Systematic analyses of epidemiological data and of other research 
ﬁ ndings show that patients with clinically relevant brain damage 
do not commit violent crimes more often than would be expected according to their proportion in the general population.
(5–7) These 
ﬁ ndings do not contradict the knowledge we have about aggressive

ﬁ ndings do not contradict the knowledge we have about aggressive 
and disruptive behaviour of certain patients with brain damage. The estimates of the frequency of such behaviours range from 18 per cent in demented patients to 60 per cent in patients with frontal lobe injuries.
(8) Most of these patients are not seen by 
forensic psychiatrists, but are treated in special institutions or in outpatient settings. Apparently, the violent behaviour of patients with brain damage does not lead to interventions by the criminal justice system as often as could be expected from the above men-tioned numbers. Similar ﬁ  ndings are reported from demented 
patients: although not appearing in criminal court ﬁ  les, aggression

patients: although not appearing in criminal court ﬁ  les, aggression 
and agitation of demented patients is a major problem in nursing homes and for caregivers of the elderly in outpatient settings. Again, exact deﬁ  nitions and robust data on how much violence 
really occurs are lacking, but estimates range from 18 to 48 per cent.
(8)
Rabins et al.(9) reported that 75 per cent of caregivers considered 
aggression as the most serious problem in agitated demented patients.
Offending and contact with the criminal justice system can be 
expected to be more frequent in patients who suffer less from cog-nitive impairments—which would prevent skilled or planned criminal activity—but rather from personality changes, like irrita-bility, impulsivity, lack of concern for others, and for the conse-quences of one’s action which is the case in frontotemporal demen-tia. Offending, but rarely violent offending, occurs sometimes as a ﬁ rst sign of this disorder.

(10) Violent crimes are sometimes associ-
ated with cognitive disorders when delusions are among the ﬁ  rst 
symptoms of a beginning dementia. Especially delusions of jeal-ousy, envy, or revenge are prone to result in violent acts, which may leave partners or neighbours as victims. These crimes contradict the previous occupational and social life of the perpetrators and are paradigmatic examples of offending as a result of a mental dis-order, leading to inculpability of the patient.
Offending can also be expected to be more frequent in patients 
between 18 and 35 years old and there fore in an age, where offending is statistically more frequent than in other age groups. Males of the

between 18 and 35 years old and there fore in an age, where offending is statistically more frequent than in other age groups. Males of the 
same age group have the highest rate of traumatic brain injury. They also belong to the age group with the highest rate of criminal-ity and especially of violent criminality. This same age and sex group also has the highest rate of substance abuse. Given the high prevalence of brain injury among young men and their propensity to use alcohol and drugs it is surprising how few are seen by foren-
sic psychiatrists or sentenced to prison. The actual numbers of such 
patients found in forensic hospitals and in prisons do not reﬂ  ect 
the high risk of violent crime by persons with brain injury. Hodgins
(11) found that only 0.4 per cent of male penitentiary

(11) found that only 0.4 per cent of male penitentiary 
inmates warranted a diagnosis of organic brain syndrome (which is a much broader term than traumatic brain injury). Similarly the proportions of patients with organic brain syndrome in forensic hospitals is below 10 per cent and not greater than that in general psychiatric hospitals.
(2, 5)
Several studies suggest that the criminality of individuals with 
brain injury may, to a large extent, be attributed to premorbid per-sonality traits, to the social disintegration which follows the injury, and hence not only to the injury itself. Kreutzer et al.
(12) studied a 
sample of 327 patients with varying severities of traumatic brain injury. Those arrested after the brain injury were more likely to have had a history of police contacts before the brain injury, than those who were not arrested.

Two disorders have to be presented in greater detail:Epilepsy, because it was historically one of the disorders of great 
concern for forensic psychiatrists and served as a model of the mentally ill offender not responsible for his crimes, and ADHD, because it is one of the disorders for which a relationship to antiso-cial behaviour and offending is most intensively researched.
Epilepsy and offending
Throughout history epilepsy has been associated with violence. Devinsky and Bear
(13) observed ‘it would be difﬁ  cult to cite, either 
from case reports or a literature review, another medical or neuro-logic illness in which aggressive behaviour is described so regularly’ . Not only seizures were frightening for lay people and caused them to consider epileptics as being cursed by gods or being possessed by witches (Malleus Maleﬁ  carum, 1487) and dangerous to others,

these patients were seen as threat because of their personality changes. At the turn of the twentieth century most lay persons and professionals believed that people with epilepsy had pathological personality traits and displayed aggression, sociopathy, and psychosis.
(14) Kraepelin too reported aggression in epileptic 
patients and mentioned that almost always an intensiﬁ  cation of 
mental irritability occurs. Jackson took it as given that epilepsy was a cause of insanity ‘ …often of a kind that brings epileptics in 
conﬂ  ict with the law’ .
(15) Even in 1973 Sjöbring(16) noted, that 
patients suffering from epileptic seizures become torpid and cir-cumstantial, sticky and adhesive, effectively tense, and ‘suffer from explosive outburst of rage, anxiety and so on’ .
Epidemiologic research,
(17) literature reviews,(18) and experi-
mental studies(19) have not supported these beliefs. Although

mental studies(19) have not supported these beliefs. Although 
epilepsy was found to be three to four times more frequent among prisoners in the United Kingdom than in the general popula-tion,
(17) their offences did not differ from those of the rest of the 
prison population. Similar ﬁ  ndings were reported from the United 
States (King and Y oung, 1978). In a extensive survey of mentally ill 11.3.3  cognitive disorders, epilepsy, adhd, and offending

SECTION 11  forensic psychiatry 1930
offenders in Germany, who had committed acts of violence, Häfner 
and Böker(5) found only 29 patients with epilepsy out of 533 hospi-

talized violent offenders (5.4 per cent of the total sample). They compared their sample to an unselected population of 3392 non-violent mentally ill hospital patients and reported that 5.2 per cent of them had also received the diagnosis of epilepsy. They concluded that epilepsy was statistically not a risk factor for violence. A thor-ough analysis of the crimes of the epileptic patients showed that marital status (single), educational level, socio-economic state, and alcohol consumption were more important risk factors than epilepsy. This is in accordance with studies in other countries. Eight of the 29 patients in the Häfner and Böker study had committed their crimes in an epileptic confusional state (which corresponds to the medico-legal term of organic automatism), but 11 had a quarrel with their victim before their offence.

Although speciﬁ  c personality changes were not conﬁ  rmed for 
epileptics in general, and some authors attributed them rather to institutionalization, brain damage, comorbid disorders, medica-tion, or social changes than to epilepsy itself, a speciﬁ  c association 
has been made between temporal lobe epilepsy (TLE) and special personality traits. 18 characteristic personality traits were summarized from the literature to constitute the Gastaut–Geschwind syndrome,
(20) among them aggression, emotional 
lability, and ‘hypomoralism’ , traits that must be considered as risk factors for offending. The empirical and neurobiological database to support an increased risk of criminality or violence even in these patients is, however, small. MRI studies found that severely aggres-sive epileptic patients were characterized by severe amygdalar atrophy or by left temporal lesions affecting the amygdala and the brain regions around them,
(21) conﬁ  rming the assumption that

(21) conﬁ  rming the assumption that 
violence has to be attributed to speciﬁ  c brain damage rather than 
to epilepsy itself.
Epilepsy is associated with a number of psychopathological and 
behavioural symptoms, among them mood changes, anxiety, rigidity, and aggression. Epidemiologic studies show a high comor-bidity with cognitive impairment, ADHD, personality disorders and psychotic disorders. Behavioural abnormalities and comorbid disorders, as well as epilepsy itself can contribute to the risk of offending in these patients.
Summarizing the results from newer empirical studies, epilepsy 
does not increase the risk for offending or violence, and the num-ber of cases, in which epilepsy was successfully used to claim incul-pability after offending violently is small.
(22) Forensic psychiatrists 
confronted with the assessment of epileptic patients who have com-mitted crimes have to consider the following key questions:
(23)

(23)
◆ Is the association between offending and epilepsy due to the occurrence of the epileptic seizure itself?
◆ Is it due to the associated brain damage that may be the cause of the seizure?
◆ Is it the result of socio-economic factors or of medication?
◆ Is the offending independent of the epilepsy and due to other criminogenic factors?
There are theoretically several possibilities, why epileptic patients 
could offend or act violently as a consequence of the disorder:
1 Aggression or impulsive acts could be a manifestation of a sei-
zure or an equivalent to a seizure (violent automatism); it could also be the reaction of the patient to negative aura experiences. Delgado-Escueta et al.
(24) collected 5400 videotaped seizures

(24) collected 5400 videotaped seizures 
and concluded that violence appears to be extremely rare event in epileptic seizures. Only 13 individuals in their sample acted violently and only three attacked other people. This study was criticized because it did not take the patient environment inter-action into account, which also plays a major role in outbreaks of aggression and which can be modiﬁ  ed by epileptic seizures.

Nevertheless, the number of cases of ictal aggression reported in the literature is small. Ictal violence erupts out of a normal non-aggressive situation within seconds, appears to be inappropriate to the circumstances, lasts for 1 to 3 min and subsides as sud-denly as it has erupted. The patient returns to consciousness immediately or returns to normality after a few minutes of con-fusion, appears to be puzzled over what has happened and has no memory of it. Complex criminal acts cannot be attributed to seizures, seizure equivalents, or epileptic automatism.
2 Violence can be the result of tension and irritability in the pro-

dromal phase of an epileptic seizure. In this case the irritability usually proceeds in waves, often triggered by the reactions of bystanders. Violence appears to be goal-directed and limited to avoid personal harm. The aggressive tension may last for several minutes up to an hour. Sometimes the patients seem out of control and do not remember their behaviour at al.
3 Postictal confusion can be associated with poriomania, 
somnambulism, and offending. Again, complex acts and adequate reactions to new situations cannot be attributed to postictal confusion or twilight states.
4 Interictal offending is quite often not associated with the disorder 
itself but with a criminal or aggressive family background, lower 
socio-economic status, and brain trauma.
(23,25) Violence can

(23,25) Violence can 
be due to epileptic psychosis, to cognitive impairment, to impulse control disorder or to personality disorder, all of which could be consequences of epilepsy, although the data on these sequels of epilepsy are not undisputed.
A recent review of the literature by Schachter
(26) can be summa-
rized to the fact that postictal aggression was rarely due to confu-sion but signiﬁ  cantly more frequent in postictal psychosis, and 
interictal aggression was associated rather with male sex, brain damage, social disadvantages, and chronic behavioural difﬁ  culties 
than with speciﬁ  c EEG ﬁ  ndings or characteristic brain scans. 
In conclusion several risk factors have to be taken into account when the offending or violence of epileptic patients is considered:
Disorder-related risk factors
◆ Brain damage
◆ Early onset of epileptic seizures
◆ Postictal psychosis

Disorder-unrelated risk factors
◆ Male sex
◆ Growing up in a criminal or aggressive environment
◆ Low socio-economic class
◆ Antisocial personality disorder
◆ Alcohol abuse

1931
In most legislations forensic psychiatrists and courts would 
agree, that the criteria proposed by Hindler,(27) would be minimal 
requirements to relate offending or violence to epilepsy:
◆ An unequivocal past history of epileptic attacks
◆ The crime is out of character with the person’s previous person ality
◆ The crime is motiveless and unpremeditated
◆ EEG studies are compatible
◆ An altered state of consciousness during the event
◆ T otal or partial amnesia for the crime
More stringent criteria were proposed by a panel of epileptolo-
gists in the United States in 1981.(24) They included videotaped 
documentations of epileptic automatism and of the presence of aggression during such seizures; also the aggressive or violent acts should be characteristic of the patient’s habitual seizures. In most Central European countries videotaped proof would not be neces-sary to attribute the offending of an epileptic to his disorder.
Attention-deﬁ  cit/hyperactivity disorder

Attention-deﬁ  cit/hyperactivity disorder 
(ADHD) and offending
Attention-deﬁ  cit/hyperactivity disorder (ADHD) is a relatively 
new diagnostic term. It has been introduced in the current form in DSM-III-R in 1987, although the condition has been known to psychiatrists for more than 100 years.
(28) Only with DSM-IV-TR 
some allowance was made to extend the diagnosis to adults(29) but 
DSM-IV-TR continued to assert that the majority of the patients loose their symptoms during late adolescence. The diagnostic crite-ria were empirically evaluated in school-children and it can be questioned whether they are appropriate for adolescents and adults. It can be questioned even more, how the association between offending and ADHD can be adequately established. The core symptoms of ADHD, inattention, hyperactivity, and impulsivity, are likely to cause social conﬂ  icts with peers and caregivers and to

lead to resentment and aggressive interactions. This dissocial func-tioning may appear as the precursor of offending in later life. A number of studies tried to investigate the relationship between ADHD in childhood and the diagnosis of antisocial personality disorder (APD) in adulthood. Although there is converging evi-dence that about 25 per cent of children with ADHD will later 
receive the diagnosis of APD,
(30,31)  and that in individuals who met 
the criteria of psychopathy according to Hare,(32) ADHD was diag-
nosed retrospectively four times more often than in the general population.
(33) Most of the studies ignore the possible impact of 
comorbid disorders, which are especially frequent with ADHD. Conduct disorder (CD), oppositional deﬁ  ant disorder (ODD), 
alcohol dependence or abuse and other drug dependence or abuse are signiﬁ  cantly more frequent in ADHD individuals than in control 
groups,
(34) and all contribute substantially to offending and to the

groups,
(34) and all contribute substantially to offending and to the 
diagnosis of APD. The longitudinal study of Satterﬁ  eld & Schell(35)
found that half of the children with a combination of ADHD and 
CD were later diagnosed as APD, while APD was only found in 12 per cent of those who had ADHD without CD in their child-hood.
(36)
A number of studies found ADHD largely overrepresented 
in prison populations, where it is calculated to be up to 10 times more frequent than in the general population.
(37,38) Except for drug-related crimes,(30) no special criminal proﬁ  le could be attrib-
uted to the disorder.
In psychiatric assessments for courts and tribunals ADHD is

In psychiatric assessments for courts and tribunals ADHD is 
rarely considered as a cause for diminished responsibility, and most offenders with this disorder will not be sent to forensic psychiatric institutions. ADHD has, however, to be regarded as risk factor for reoffending, especially if it is or was combined with a conduct dis-order. Prisoners with ADHD had been reconvicted four times more often than other prisoners.
(39)
Barkley, R.A. (2006). Attention-deﬁ  cit/hyperactivity disorder  (3rd edn). 
The Guilford Press, New Y ork.
Etinger, A.B. and Kanner, A.M. (2007). Psychiatric issues in epilepsy
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21. van Elst, L.T., Woerman, F.G., Lemieux, L., et al. (2000). Affective 
aggression in patients with temporal lobe epilepsy: a quantitative MRI study of the amygdala. Brain ,123, 234–43.
22. Treiman, D.M. (1999). Violence and the epilepsy defense. Neurologic 
Clinics ,17, 245–55.
23. Herzberg, J.L. and Fenwick, P .B.C. (1988). The aetiology of

23. Herzberg, J.L. and Fenwick, P .B.C. (1988). The aetiology of 
aggression in temporal-lobe epilepsy. The British Journal of Psychiatry ,
153, 50–5.
24. Delgado-Escueta, A., Mattson, R., and King, L.M. (1981). The nature 
of aggression during epileptic seizures. The New England Journal of 
Medicine ,305, 711–6.
25. Stevens, J.R. and Hermann, B. (1981). T emporal lobe epilepsy, 
psychopathology and violence: the state of evidence. Neurology ,
31, 1127–32.
26. Schachter, S.C. (2007). Aggression in epilepsy. In Psychiatric issues in 
epilepsy  (2nd edn) (eds. A.B. Etinger and A.M. Kanner), pp. 306–20. 
Wolters Kluwer, Philadelphia.
27. Hindler, C.G. (1989). Epilepsy and violence. The British Journal of 
Psychiatry ,155, 246–9.
28. Hechtman, L. (2004). Attention-deﬁ  cit/hyperactivty disorder. In 
Kaplan & Sadock comprehensive textbook of psychiatry  (8th edn)

Kaplan & Sadock comprehensive textbook of psychiatry  (8th edn) 
(eds. B.J. Sadock and V .A. Sadock), pp. 3183–98. Lippincott, Williams & Wilkins, Baltimore.29. McGough, J.J. (2004). Adult manifestations of attention-deﬁ  cit/
hyperactivity disorder. In Kaplan & Sadock comprehensive textbook of 
psychiatry  (8th edn) (eds. B.J. Sadock and V .A. Sadock), pp. 3198–204. 
Lippincott, Williams & Wilkins, Baltimore.
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up of hyperactive children: antisocial activities and drug use. Journal of 
Child Psychology and Psychiatry ,45, 195–211.
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Attention problems and conduct problems though retrospective 
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attention-deﬁ  cit/hyperactivity disorder in male young prison

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21, 17–21.

11.4
Mental disorders 
among offenders in correctional settings
Incontrovertible evidence now exists to show that the prevalence of 
mental disorders among prisoners far exceeds that found in the general community. A surprising concordance is emerging from several large international studies to show that, in western devel-oped societies at least, the rates of major mental disorders in pris-ons are quite consistent. This chapter will provide an overview of relevant research examining rates of mental illness in prisons with those found in the community. Some observations regarding trends and implications for prisons also will be provided.
At the outset it is useful to reﬂ  ect on the scope of illnesses which

At the outset it is useful to reﬂ  ect on the scope of illnesses which 
have been subsumed under the ‘mental disorder’ umbrella as it has been applied to the prison research. Most of the research that exists has focussed serious mental illnesses within the Axis I disorders—namely psychotic illnesses, mood disorders, and anxiety disorders. Considerable attention has been paid regarding the prevalence of personality disorders within prisons. Over the past 20 years much of that work has investigated antisocial or dissocial personality disorder and psychopathy.
(1) By comparison, relatively little atten-

tion has been paid to other personality disorders. A growing area of importance concerns substance abuse and dependence disorders and, of course, co-occurring substance use and mental illness disorders. Considerable research also exists exploring the preva-lence of mental retardation or intellectual disabilities in prison. Thereafter, fragments of research exist exploring any number of mental syndromes and conditions. The focus of this chapter will be on the major mental disorders which fall into Axis I. Some mention will be made of substance use disorders and personality disorders. In addition, with the growing number of women in prisons, infor-mation will be provided regarding this important group.
The prevalence of mental illness among 
male and female prisoners
Recent research exists from Britain and Wales that shows that the

Recent research exists from Britain and Wales that shows that the 
prevalence of mental illness in prisons is many times greater than that found in the community. Brugha and colleagues
(2) compared 
rates of mental illness among some 3, 000 remanded and sentenced male and female prisoners in Britain and Wales and more than 10, 000 community residents in Great Britain. The rate of 
psychotic illnesses in the community was 4.5 per 1, 000 (0.045 per 
cent) compared with 52 per 1, 000 in prisons (0.52 per cent). While 
the ten-fold increase in prevalence from the community to the prisons was remarkable, the results revealed further that the preva-lence rate of psychotic illness for female prisoners was an astonish-ing 110 per 1, 000 (0.11 per cent), compared to 50 per 1, 000 for males (0.05 per cent).
One of the key studies that has helped provide information

One of the key studies that has helped provide information 
regarding the rate of mental illness in gaols and prisons is a meta-
analysis conducted by Fazel and Danesh
(3) that was published 
inThe Lancet . Their analyses included 62 studies that included 
22, 790 prisoners. The majority of prisoners (81 per cent) were male. Nonetheless, enough studies that included women prisoners were available to provide information regarding the rate of mental disorder among them. Data from the Fazel and Danesh meta-analysis are presented in Table 11.4.1. The results show that approx-imately one in seven prisoners have a psychotic illness or major depression. As the authors report, this is between two and four times greater than would be expected in the general population. 
Table 11.4.1  Representative prevalence of mental illness and 
personality disorder among male and female prisoners (international 
samples)
Disorder Males  per cent 
(95 per cent C.I.)Females  per cent 
(95 per cent C.I.)

samples)
Psychotic Illness(k = 49, N = 19,011)3.7 (3.3–4.1) 4 (3.2–5.1)
Major Depression
(k = 31, N = 10,529)10 (9–11) 12 (11–14)
Personality Disorder
(k = 28, N = 13,844)65 (61–68) 42 (38–45)
Antisocial Personality 
Disorder47 (46–48) 21 (19–23)
k = number of studies; N = number of subjects; C.I. = Conﬁ  dence Intervals.
Source: Fazel & Danesh (2002).

SECTION 11  forensic psychiatry 1934
With respect to personality disorders, half of males and approxi-
mately 20 per cent of females are found to have a personality disorder—which is ten times greater than would be seen in the community.
There was some variability across studies, some (but not all) 
of which was explained by differences between research that used validated diagnostic procedures (3.5 per cent) and those that did not (4.3 per cent). Studies from the USA also showed higher pre-valence rates than elsewhere. Psychosis among female prisoners was found to be slightly higher than that in males (4.0 per cent c.f.
3.7 per cent).
(3)
A limitation of the Fazel and Danesh(3) meta-analysis is that 
relatively limited information was provided regarding the type and nature of mental illness. Brinded, Simpson, Laidlaw, Fairley, and Malcolm
(4) reported the results of one of the most well con-

ducted studies on the prevalence of mental illnesses among inmates ever published. All female sentenced and remanded inmates and 
a random sample of 18 per cent of sentenced male inmates in New Zealand were interviewed. Interviewers used standardized measures to identify inmates with mental illnesses and personality disorders. The final sample consisted of approximately 1 200 inmates. The results of prevalence rates for mental disorder in the last month are presented in Table 11.4.2.
As the results in Table 11.4.2 show, the prevalence rates obtained 
by Brinded and colleagues
(4) in New Zealand essentially parallel 
those obtained by the Fazel and Danesh(3) meta-analysis. The New

those obtained by the Fazel and Danesh(3) meta-analysis. The New 
Zealand results, however, include data for post-traumatic stress disorder, substance abuse, and dependence disorders. As with psy-chosis and major depression, the prevalence rates of the other disorders is signiﬁ  cantly greater than what would be seen in the 
Of late, increased attention is being paid to the prevalence of 
mental disorders among female inmates.
(5) In recent years, the rate 
of growth among women in custody has far surpassed the growth rate for male prisoners. For example, data show that in the 10 years 
ending 2005, the percentage of women in prisons in the United States has increased by 57 per cent, compared to a growth rate of 34 per cent for men during the same period.
(6) Similar ﬁ  ndings 
exist in Australia, where research shows that the number of women

exist in Australia, where research shows that the number of women 
in prison increased by 66 per cent from 1991 to 1999, while it increased by 24 per cent for men during the same period.
(7)
Even more than for male prisoners, ‘the prevalence of childhood 
and adulthood sexual and violent victimization, poverty, and poor educational and employment attainment reported by female inmates is nothing short of alarming’ .
(8) While a compre-
hensive review of the studies of mental illness among women offenders is beyond the scope of this chapter, Ogloff and Tye
(5)
have shown that the prevalence rates of mental disorders for women is now surpassing those identiﬁ  ed for men in most published 
studies. This is particularly the case for mood disorders and anxiety disorders.
Implications, service needs, opportunities

The cause of the relatively high prevalence of mental illness among people in the prison system has been sometimes attributed to the deinstitutionalization movement that has occurred in mental health over the past 20 years. The contention that the mentally ill are entering gaols in increasing numbers has not been accepted by all, however.
(9) It has been proposed that it is simply heightened 
awareness among professionals and the public of the problem of mentally ill in the gaols that has resulted in the perception that they are entering in increasing numbers.
(10) In a recent study investigat-
ing the criminal offence history of every person in Victoria with schizophrenia in the public mental health registry in ﬁ  ve year 
cohorts from 1975 to 1995, Wallace, Mullen, and Burgess
(11) found

(11) found 
that there was no subsequent increase in offence rate by year for those with schizophrenia, while the offence rate for the matched comparison group of people in the community without a mental illness increased signiﬁ  cantly over the period. This is particularly 
interesting since during that time the process of deinstitutionaliza-tion was completed in Victoria. Indeed, there are no more psy-chiatric hospitals in Victoria (except for a 100 bed secure forensic psychiatric hospital).
A number of contributing factors have been identiﬁ  ed that help

A number of contributing factors have been identiﬁ  ed that help 
explain the high numbers of people with mental illnesses in the criminal justice system. Considerable concern has been raised about the capacity of community-based mental health services to address the needs of mentally ill offenders. Community-based 
mental health services work best for those who have reasonable 
connections and support within the community. Unfortunately, offenders (especially imprisoned offenders) tend to be poorly inte-grated into the community
(12) and have poor access to a range of 
support services including accommodation, income support, health and mental health.
(13, 14)
While the presence of mentally ill people in the criminal justice

(13, 14)
While the presence of mentally ill people in the criminal justice 
system presents challenges and raises concerns, the fact is that the justice system provides an opportunity to identify and deliver treat-ment to people who are otherwise likely to remain outside the reach of services. As such, it has been suggested that justice mental health services present an opportunity for identifying those with mental illnesses and making services available to them that would otherwise be non-existent.
(10) Accordingly, taking a population Table 11.4.2  Prevalence rates for mental disorder in last month 
(New Zealand samples)
Diagnosis Women 
N = 167 
n (per cent)Remanded 
Men N = 441 
n (per cent)Sentenced 
Men N = 636 
n (per cent)
Mental Illness
  Schizophrenia and related 
disorders  7 (4.2) 15 (3.4) 14 (2.2)
 Bipolar affetive disorder  2 (1.2)  4 (1.0)  7 (1.1)

Men N = 441 
Men N = 636 
 Major depression 18 (11.1) 47 (10.7) 38 (5.9)
  Obsessive-compulsive 
disorder  7 (4.3) 22 (5.0) 21 (4.8)
 Posttraumatic stress disorder 27 (16.6) 42 (9.5) 55 (8.5)
Substance-Related Disorders
 Alcohol abuse  7 (4.3) 25 (5.7)  8 (1.2)
 Alcohol dependence  4 (2.5) 19 (4.3)  3 (0.5) Cannabis abuse  6 (3.7) 38 (8.6) 27 (4.2) Cannabis dependence  0 (0)  0 (0)  0 (0)
 Other abuse/dependence .  6 (3.7) 27 (6.1) 12 (1.9)
Reproduced from Brinded et al. Prevalaence of pyschiatric disorders in New Zealand 
Prisons: A national study. Australian and New Zealand Journal of Psychiatry , 35, 166–73, 
copyright 2001, John Wiley & Sons, Inc.

1935
health perspective, efforts to identify and treat those with mental 
illnesses who are entering the criminal justice system can help provide much needed services to this otherwise under-serviced population.
Service development and provision to 
mentally ill offenders in prisons
Although it is beyond the scope of the chapter to discuss the pro-
vision of mental health services to prisoners, it may be helpful here to outline some of the requirements for services. The service model outlined here has been detailed elsewhere in the litera-ture.
(10) The service model recommended for use in prisons 
consists of six components outlined below, the nature and extent of which will vary depending on the needs arising in each institution.
Intake screening
A two-tier evaluation process is recommended. The ﬁ  rst step 
involves a brief mental health screening for every inmate upon admission. Second, those prisoners identiﬁ  ed as being mentally ill

involves a brief mental health screening for every inmate upon admission. Second, those prisoners identiﬁ  ed as being mentally ill 
are referred to mental health professionals for a more complete assessment. All prisoners should be screened for mental illness soon after admission to a correctional facility (within the ﬁ  rst 24 h). 
The Jail Screening Assessment Tool (JSAT;  Nicholls et al., 2005) was 
developed to screen people being admitted to gaols for mental illness, as well as self-harm risk and risk of harm to others. The JSAT is administered by psychiatric nurses or other mental health professionals and takes approximately 20 minutes. It is validated for both male and female prisoners.
Ongoing monitoring/screening of prisoners
A process must be in place for ensuring that prisoners are monitored, both formally and informally. This should include self-referrals and referrals by all prison staff.

Comprehensive psychodiagnostic assessment
Comprehensive assessments by psychiatrists or clinical psycholo-gists are required for all prisoners exhibiting symptoms of mental illness. The examination should include consideration of whether the prisoners who are acutely mentally ill should receive treatment in the institution or be transferred to hospital.
Mental health treatment
Once assessed as having a mental illness, the prisoner should be referred to an appropriate treatment program within the correc-tional facility or correctional system if possible and practical. The size of the gaol and its mandate affects the type of service available. Services should be at the standard available in the community.
Gradual post-release monitoring/supervision and 
continuity of services

Treatment should continue post-release in the community. The 
transition back to the community is often difﬁ  cult, as evidenced 
by high recidivism rates and ongoing illness. Service needs for mentally ill people leaving prison include initiating psychiatric treatment and psychosocial services with a community mental health agency, locating housing, and ﬁ  nding employment.Programme evaluation
Given the complexity of mental health services in prisons, it is

Given the complexity of mental health services in prisons, it is 
critical that programmes are evaluated on an ongoing basis (e.g. Elliot, 1997). Such evaluations are as important as the other com-ponents in achieving assessment and delivery of mental health services. Also, wherever possible, assessment must be linked with treatment. Ongoing evaluations of the effectiveness of the assessment/treatment decisions should be built into the system. Evaluation informs decision-makers about the outcome of their decisions. Over time, this feedback can lead to improvements in the assessment, referral, and treatment phases of the model. Data on the base rates of mental disorder among women in custody- and the number of female prisoners who fall into the MDO categories—also can prove valuable in planning for future treatment needs .
Fazel, S., and Danesh, J. (2002). Serious mental disorder in 23 000 prisoners: 
a systematic review of 62 surveys. Lancet ,359, 545–50.

Ogloff, J.R.P (2002). Identifying and accommodating the needs of mentally 
ill people in gaols and prisons. Psychiatry, Psychology, and Law ,
9, 1–33.
Sheehan, R., McIvor, G., Trotter, C. (eds) (2007). What works with women 
offenders . Willan Publishing, Devon, UK.
 1. Ogloff, J.R.P . (2006). The Psychopathy/Antisocial Personality Disorder 
conundrum. Australian and New Zealand Journal of Psychiatry ,
40, 519–28.
 2. Brugha, T., Singleton, N., Meltzer, H., et al. (2005). Psychosis in the 
community and in prisons: A report from the British National Survey of Psychiatric Comorbidity. American Journal of Psychiatry,
162, 774–80.
 3. Fazel, S., Danesh, J. (2002). Serious mental disorder in 23 000 prisoners: 

 4. Brinded, P .M.J., Simpson, A.I.F., Laidlaw, T.M., (2001). Prevalence 
of psychiatric disorders in New Zealand prisons: A national study. Australian and New Zealand Journal of Psychiatry ,35, 166–73.
 5. Ogloff, J., Tye, C. (2007). Responding to mental health needs of 
women offenders. In What works with women offenders . (eds. 
R. Sheehan, G. McIvor, C. Trotter), pp. 142–81 Willan Publishing, Devon, UK.
 6. Harrison, P . and Beck, A. (2006). Prisoners in 2005 . Washington, DC: 
US Bureau of Justice Statistics Bulletin NCJ 215092.
 7. Cameron, M. (2001). Women Prisoners and Correctional Programs, 
Trends and Issues in Crime and Criminal Justice , 194, Canberra, ACT: 
Australian Institute of Criminology.
 8. Nicholls, T., Lee, Z., Corrado, R., et al. (2004). Women inmates’ mental

 8. Nicholls, T., Lee, Z., Corrado, R., et al. (2004). Women inmates’ mental 
health needs: Evidence of the validity of the Jail Screening Assessment 
Tool (JSAT), International Journal of Forensic Mental Health ,
3(2),167–84.
 9. Monahan, J., Caldeira, C., Friedlander, H. (1979). The police 
and the mentally ill: A comparison of arrested and committed persons. International Journal of Law and Psychiatry ,2,
509–18.
10. Ogloff, J.R.P . (2002). Identifying and accommodating the needs of 
mentally ill people in gaols and prisons. Psychiatry, Psychology, and 
Law,9, 1–33.
11. Wallace, C., Mullen, P .E., Burgess, P . (2004). Criminal offending 
in schizophrenia over a twenty-ﬁ  ve year period marked by 11.4 mental disorders among offenders in correctional settings

SECTION 11  forensic psychiatry 1936
deinstitutionalization and escalating comorbid substance abuse. 
American Journal of Psychiatry, 161, 716–27.
12. Makkai, T., McGregor, K. (2003). Drug Use Monitoring in Australia: 
2002 Report on Drug Use Among Police Detainees. Research and 
Public Policy Series  No. 47. Australian Institute of Criminology, 
Canberra.13. Baldry, E. (2003). Ex-prisoners, housing and social integration. Parity ,
16, 13–15.
14. Travis, J., Waul, M. (2003). From prison to home: The effect of 
incarceration and re-entry on children, families, and communities .
The Urban Institute. Washington, DC.

There is a widespread public perception of the mentally ill as 
violent.(1,2) Until the early 1980s there was a consensus view that 
patients with severe mental illness were no more likely to be violent than the general population. Emerging evidence from various coun-tries over the past two decades, however, has established a small, yet signiﬁ  cant, association between mental illness and violence.
Large-scale birth cohort studies, such as a 30 year follow-up of 
an unselected Swedish birth cohort, show a signiﬁ  cantly increased 
risk of violent offences in men and women in the presence of major mental disorder.
(3) Community epidemiological studies in New 
Yo r k(4) and in Israel(5) again show an increased risk of violence in 
psychiatric patients. An important contribution to this ﬁ  eld is data

psychiatric patients. An important contribution to this ﬁ  eld is data 
from the Epidemiological Catchment Area study, showing that major mental illness increases the rates of violence over a 12-month period from a 2 per cent base rate to 8 per cent, but co-morbid substance abuse increases this rate further to 30 per cent.
(6)
Co-morbid substance abuse and personality disorder substantially increase the risk of violence, as demonstrated in the MacArthur Risk Assessment Study which showed rates of violence in discharged psychiatric patients of 18 per cent in those with major mental dis-order, 31 per cent with major mental disorder and co-morbid sub-stance abuse, and 43 per cent in those with personality disorder and co-morbid substance abuse.
(7)
Public fears are often fuelled by media reporting of high-proﬁ  le

(7)
Public fears are often fuelled by media reporting of high-proﬁ  le 
cases of homicide by people with mental illness.(8) Despite indica-
tions that rates of homicide among the mentally ill are relatively constant across countries,
(9) studies of mental disorder in people 
convicted of homicide show that 8.7 per cent of homicides in New Zealand are ‘abnormal’ ,
(10) yet evidence from Canada indicates 
that 35 per cent of perpetrators are mentally unwell.(11) Indeed 
rates ranging from 8 to 70 per cent have been found, varying with different deﬁ  nitions of mental disorder.
(12)
The National Conﬁ  dential Inquiry into Suicide and Homicide by 
People with Mental Illness was established at the University of Manchester in 1996. The core work of the Inquiry is to establish rates of mental disorder in homicide and the clinical care received by those in contact with services.
General population homicides

There are 500–600 homicides annually in England and Wales. Perpetrators and victims are predominantly young males, especially when the victim is unknown to the perpetrator. In such ‘stranger 
homicides’ perpetrators are less likely to have a lifetime history of 
mental illness, symptoms of mental illness at the time of the offence, or contact with mental health services.
In the UK the total number of both total homicides and stranger 
homicides increased between1973 and 2003 but neither category increased in people with mental illness.
(13) Similar trends have been 
noted in work from both the UK,(14) and in other countries.(10)
The commonest method of homicide is with a sharp instrument; 
shooting is relatively rare, accounting for less than 1 in 10 homicides in the UK.
Around half of all convictions are for murder and just under 
half for manslaughter. One in 25 receives a verdict of Section 2 manslaughter, diminished responsibility.
Infant homicide

Despite an increasing rate of homicides in the general population, convictions for infanticide and the rate of infant homicide has remained relatively constant, at around 4.5 per 100 000 live births.
(15) Infanticide has become a generic term for killing of 
infants, even though the criminal charge in England applies to a 
crime for which only a woman can be indicted.
Although the risk of homicide is higher in the ﬁ  rst year of their 
life than at any other time, the rarity of infant homicide in absolute 
numbers means that there is a lack of high quality, systematic data 
at a population level which incorporates clinical characteristics.(16)
Data from the National Conﬁ  dential Inquiry from 1996 to 2001 
shows that 1 in 25 of the 2665 homicide perpetrators identiﬁ  ed

shows that 1 in 25 of the 2665 homicide perpetrators identiﬁ  ed 
were convicted of infant homicide. Half of these infants were killed by their father and around a third by their mother. A quarter of perpetrators had symptoms of mental illness at the time of the offence and a third had a lifetime history of mental illness. Perpetrators of neonaticide were predominantly young, unmarried mothers experiencing symptoms of dissociation at the time of the homicide.
There were signiﬁ  cant differences between male and female 
perpetrators, with males being more likely to have previous convic-tions for violent offending. Females were more likely to kill within a month of the birth and they were more likely to have affective disorder and symptoms of mental illness at the time of the offence but few of these women were under the care of mental health services. Homicide offenders including 
mass murder and infanticide

Nicola Swinson and Jennifer Shaw11.5

SECTION 11  forensic psychiatry 1938
Most males received a custodial sentence, whereas three quarters of 
women received a community sentence or hospital disposal.(16)
Multiple homicides
Multiple homicides, in particular serial homicides, have generated a great deal of public and media interest over recent decades yet this phenomenon is rare in the UK. The rarity of these events means that there is a lack of empirical evidence about the charac-teristics of perpetrators and victims in the UK, with most evidence emanating from the United States. Even then, however, there is an absence of systematic, robust evidence, with many studies being limited by small sample size.
Most deﬁ  nitions of multiple homicides include three criteria; 
number of victims, which can vary from 2 to 10 in different deﬁ  ni-
tions,
(17) time, and motivation. The temporal relationship distin-

tions,
guishes subcategories: mass murder consisting of a single episode and location, with serial, and spree murders occurring over time in separate locations. The latter two are differentiated by an emotional ‘cooling-off’ period, which is present in serial homicide. Other authors have discussed motivation, such as sexual gratiﬁ  cation and 
internal psychological gratiﬁ  cation, but the lack of robust evidence 
means that it seems premature to include motivation as part of any such deﬁ  nition.
(17)
Mass murder has been classiﬁ  ed by victim type such as family 
annihilators and classroom avengers. Mullen(18) proposed a cate-
gory of ‘autogenic (self-generated) massacre’ , which encompassed perpetrators indiscriminately killing people in pursuit of a highly personal agenda, arising from their own speciﬁ  c social situation

and psychopathology. They were characterized by social isolation, being bullied in childhood and personality traits such as suspi-ciousness, obsessional behaviour, grandiosity, and persecutory beliefs. He concluded that these murders are essentially murder-suicides, where the intention is to kill as many people as possible before killing themselves. It would now appear, particularly with recent events in Virginia, that this form of multiple homicide is an established form and concerningly appears to becoming more common. Cantor et al.
(19) propose that media-related modelling is 
a potential factor in the emergence of this crime, with perpetrators often seeing themselves as lone warriors, themselves modelled on media images, and well informed about previous, similar, massacres.
An exploratory study, incorporating a nested case control study,

An exploratory study, incorporating a nested case control study, 
showed that serial homicide offenders were more likely to be male dominated, compared with single homicide offenders, and were more likely to use strangulation. Moreover, victims of serial murders were signiﬁ  cantly more likely to be females who were 
unknown to the perpetrator and the motivation being sexual.
(17)
Unfortunately most classiﬁ  cation systems of serial murder, includ-
ing the FBI classiﬁ  cation, have been criticized as being inherently 
ﬂ awed due to weak operational deﬁ  nitions and unsubstantiated 
assumptions regarding behaviour and characteristics.(20)
There is, unfortunately, a lack of robust evidence regarding 
multiple homicides. There seem to be clear similarities between 
serial and mass murderers, but also fundamental differences. Mass 
murderers appear more likely to use ﬁ  rearms as a method, whereas

murderers appear more likely to use ﬁ  rearms as a method, whereas 
serial murderers tend to kill in a more personal manner, using methods that afford greater physical proximity, such as strangulation, in addition to a greater propensity for female victims. Clinically, some evidence indicates that a substantial proportion of mass 
murderers have a severe mental illness, often a psychotic illness. On the other hand, it is proposed that serial murderers can be dis-tinguished by lower levels of severe mental illness and the presence of higher degrees of psychopathy.
(21)
Female perpetrators of homicide
Around 1 in 10 perpetrators of homicide in England and Wales are female,
(13) which is consistent with data from other countries, such 
as Finland.(22) Stranger homicide by females is rare. In one-quarter

as Finland.(22) Stranger homicide by females is rare. In one-quarter 
of cases the victims are the perpetrators’ own children and a cur-rent or former partner in over a third.
As with men the commonest method is stabbing, although 
females are proportionally more likely to use suffocation or poisoning when compared with men.
There are no clear gender differences in the proportion of those 
with severe mental illness but females are proportionally more likely to have a diagnosis of alcohol or drug dependence than men. Females are less likely to receive a prison sentence and are more commonly placed on a hospital or community rehabilitation order.
(13)
Homicide by older people
Homicides perpetrated by the elderly are exceptionally rare. In England and Wales they account for less than 1 in 50 homicides. The male to female ratio in perpetrators over 65 years is the highest of all age groups, at 19:1.
(13)

(13)
There is a distinct lack of robust evidence regarding homicide in 
this population. Elderly spouse homicides have been described by Knight
(23) as involving a couple perceived to have a close, caring 
relationship with the homicide of the wife, by the husband, occur-ring in an abrupt and unexpected manner. Depression is well rec-ognized in elderly homicides, not infrequently with associated delusions of impoverishment and ruin. Perpetrators are often in care giving roles with physical or psychiatric disability in the vic-tim. The homicide is often followed by suicide of the offender.
(24)
Those over 65 years are more likely to receive a hospital order or 
community disposal, than a custodial sentence.(13)
Perpetrators of homicide with mental health 
service contact
The aim of the National Conﬁ  dential Inquiry is to collect detailed 
clinical information on people convicted of homicide, focusing on those with a history of contact with mental health services.

The inquiry collects a national consecutive case series of patient

The inquiry collects a national consecutive case series of patient 
homicides occurring since April 1996. Data collection involves col-lecting information on all homicides from the Home Office Homicide Index, which includes details of the perpetrator, victim, and method used. Where available, psychiatric reports prepared for the trial are obtained. Antecedent data (of previous offences) is col-lected from the National Crime Operations Faculty. Details on each case are submitted to mental health services in each indivi dual’s district of residence and adjacent districts to identify those with a history of mental health service contact. These individuals become Inquiry cases. Information on trust Inquiry cases is obtained from clinical teams via a comprehensive questionnaire sent to the con-sultant psychiatrist.

1939
In the UK around 1 in 10 people convicted of homicide have 
been in recent contact with mental health services. In most of these cases the responsible service is a general adult psychiatry service, rather than a specialist service. The remaining cases are under alco-hol and drug services, child and adolescent services, and forensic psychiatry services. Around one in ﬁ  ve cases have had lifetime 
contact with services. This compares with data from other coun-tries, such as Australia, where one in three perpetrators has had contact with psychiatric services.
(25)
Of those in contact with mental health services in England and 
Wales, the most common diagnosis is schizophrenia, although less than half have severe mental illness (schizophrenia or affective disorder). There are high rates of co-morbid alcohol and drug dependence and personality disorder. Only one-third have previ-ous admissions under the Mental Health Act (1983).

A high proportion of these patients have a history of violence, 
including convictions for violence, which, worryingly, are not doc-umented in the case notes in a number of cases. Similar ﬁ  ndings 
regarding the prevalence of violence were found in an examination of ﬁ ndings from public inquiries into homicides in the UK.
(26)
A small number of homicides are committed by patients who have 
previously been on a restriction order because of a violent offence.
Around half of those prescribed medication are non-compliant 
or disengaged from services at the time of the offence and relatively few are receiving any psychological intervention.
(13)
Perpetrators with schizophrenia
There is a well documented increased risk of violence in those with schizophrenia.
(27) This has been shown in studies from the UK(28)
and in other countries such as New Zealand(29) and Denmark.(30)
Around 1 in 20 perpetrators of homicide have a diagnosis of

Around 1 in 20 perpetrators of homicide have a diagnosis of 
schizophrenia, a half have been in recent contact with services and one-third have never had any service contact.
(13) These ﬁ  ndings are 
broadly consistent with other UK data from remand prisoners,(31)
and with data from other countries with rates of schizophrenia ranging from 7 per cent in Finland,
(32) 7.5 per cent in Australia(25)
to 12.6 per cent in Canada.(11)
Of those with recent contact one-ﬁ  fth have a secondary diagno-

sis, commonly personality disorder or substance dependence, and a history of violence is common. Nearly a half have a history of vio-lence when psychotic, around one-quarter are psychotic at the time of the homicide. Victims are most commonly family members; in less than one in six cases the victim is a stranger. Similar rates of stranger homicide by the mentally ill are found in Australia and New Zealand.
(10) The majority of these patients have symptoms of 
mental illness at the time of the homicide and one in four receives a verdict of diminished responsibility. Of those not in contact with services, the vast proportion are psychotic at the time of the offence.
(13)
It is of concern that nearly one-third of all perpetrators with 
schizophrenia receive a prison disposal.
Despite clear evidence of an increased risk associated with

(13)
Despite clear evidence of an increased risk associated with 
schizophrenia it is important to present a balanced view to prevent unnecessary stigmatization. The proportion of violent crime in society which is attributable to schizophrenia is consistently less than 10 per cent.
(27) Wallace et al.(25) showed an increased risk of 
serious violent offending in males with schizophrenia of ﬁ  ve times 
that of the general population. However, he also highlights data which indicate that, in any given year, 99.97 per cent of all those 
with schizophrenia will not be convicted of a serious violent offence, and that the probability of patients with schizophrenia committing homicide is extremely low.

Nearly one in three Inquiry cases were seen during the week before the homicide, a similar proportion within 1–4 weeks and the remainder between 1–12 months. A substantial proportion had mental state abnormalities at ﬁ  nal contact, often distress, depres-
sive symptoms, hostility, or increased use of alcohol or drugs. Despite this immediate risk was judged to be low or absent in 88 per cent cases at the last contact.
There are clear difﬁ  culties in predicting risk of serious violence, 
given the rarity of its’ occurrence alongside the high prevalence of risk factors such as substance abuse and a history of violence within the patient population. In an examination of ﬁ  ndings from public inqui-

ries into homicides it was shown that only 28 per cent of homicides were judged ‘predictable’ , yet 65 per cent were seen as ‘preventable’ . ‘Preventability’ was conferred by ‘improved mental health care’ .
(26)
Use of enhanced CPA to manage risk
In the National Conﬁ  dential Inquiry sample from 1999 to 2003, 
nearly three quarters of those with recent contact were not receiv-ing care under the provisions of enhanced Care Programme Approach (CPA), including a substantial proportion of patients at high risk such as those with schizophrenia, personality disorder, a history of detention under Mental Health Act legislation, or a pre-vious history of violence. Furthermore, one-third of those with severe mental illness, a history of violence, and detention under the Mental Health Act were not under enhanced CPA.
Among those who were being cared for under the provisions of 
enhanced CPA, a signiﬁ  cant number were non-compliant with

enhanced CPA, a signiﬁ  cant number were non-compliant with 
medication or disengaged from services at the time of the offence. It seems, therefore, that even if risk is recognized high-risk patients are not receiving the intensive care, commensurate with their level 
of risk, in the community.
(13)
Preventability
Clinicians identiﬁ  ed one case in ﬁ  ve in recent contact where the 
homicide could potentially have been prevented. Factors viewed as increasing the chance of preventing the homicide included a diag-nosis of schizophrenia, multiple previous admissions, and deten-tion under the Mental Health Act. Factors which were seen to have made the homicide less likely were better patient compliance; closer contact with patient’s family; closer patient supervision; improved staff communication; and better staff training.
(13)
Longitudinal trends
When longitudinal data from the National Conﬁ  dential Inquiry

(13)
When longitudinal data from the National Conﬁ  dential Inquiry 
from 1997 to 2003 was examined it was apparent that, despite a rise in the homicide conviction rate in the general population, there has been no consistent change in rates of mental illness symptomatol-ogy at the time of the offence, contact with mental health services, 
lifetime history of mental illness, or speciﬁ  cally schizophrenia. 
Signiﬁ  cant upward trends can be seen in the number of perpetra-
tors with a history of drug and alcohol misuse, in particular the use 11.5 homicide offenders including mass murder and infanticide

SECTION 11  forensic psychiatry 1940
of cocaine and crack cocaine. There has been a signiﬁ  cant decrease 
in those receiving a verdict of diminished responsibility but, surpris-ingly, no change in rates of those receiving a hospital order.
(13)
http://www.medicine.manchester.ac.uk/suicideprevention/nci/ (the website 
for the National Conﬁ  dential Inquiry which is regularly updated).
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 2. Crisp, A.H., Gelder, M.G., Rix, S., et al.  (2000). Stigmatisation of

33, S7–12.
 2. Crisp, A.H., Gelder, M.G., Rix, S., et al.  (2000). Stigmatisation of 
people with mental illness. The British Journal of Psychiatry ,
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 3. Hodgins, S. (1992). Mental disorder, intellectual deﬁ  ciency, and crime: 
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behaviour of mental patients reconsidered. American Sociological 
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Psychiatry ,41, 761–70.

 7. Steadman, H.J., Mulvey, E.P ., Monahan, J., et al. (1998). Violence by 
people discharged from acute psychiatric inpatient facilities and by others in the same neighbourhoods. Archives of General Psychiatry ,
55, 1–9.
 8. Ritchie, J., Dick, D., and Lingham, R. (1994). Report of the inquiry 
into the care and treatment of Christopher Clunis . Stationery Ofﬁ  ce, 
London.
 9. Coid, J. (1983). The epidemiology of abnormal homicide and murder 
followed by suicide. Psychological Medicine ,13, 855–60.
10. Simpson, A.I.F., McKenna, B., Moskowitz, A., et al. (2004). Homicide 
and mental illness in New Zealand, 1970–2000. The British Journal of 
Psychiatry ,185, 394–8.
11. Cote, G. and Hodgins, S. (1992). The prevalence of major mental 
disorders among homicide offenders. International Journal of Law and 
Psychiatry ,15, 89–99.

12. Woodward, M., Nursten, J., Williams, P ., et al. (2000). Mental disorder 
and homicide: a review of epidemiological research. Epidemiologiae 
Psichiatria Sociale ,9, 171–89.13. Appleby, L., Shaw, J., Kapur, N., et al. (2006). Avoidable deaths: ﬁ  ve year 
report by the national conﬁ  dential inquiry into suicide and homicide 
by people with mental illness. Published online 2006.
14. Taylor, P .J. and Gunn, J. (1999). Homicides by people with mental 
illness: myth and reality. The British Journal of Psychiatry ,174, 9–14.
15. Home Ofﬁ
 ce. (2005). Crime in England and Wales 2003/2004. 
In Homicide and gun crime, Supplementary  Volume 1 (ed. D. Povey). 
National Statistics, London.
16. Flynn, S., Shaw, J., and Abel, K. Homicide of infants: a crossectional 
study . (submitted).

17. Kraemer, G.W., Lord, W.D., and Heilbrun, K. (2004). Comparing 
single and serial homicide offenses. Behavioral Sciences & the Law ,
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Sciences & the Law ,22, 311–23.
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civil massacre. TheJournal of the American Academy of Psychiatry and 
the Law ,28, 55–63.
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classiﬁ  cation approach to proﬁ  ling violent behaviour. CRC Press, 
Boca R aton, FL.
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and mass homicide. Behavioral Sciences & the Law, 22,289–90 .
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22. Putkonen, H., Komulainen, E.J., Virkkunen, M., et al. (2003). Risk of 
repeat offending among violent female offenders with psychotic and personality disorders. The American Journal of Psychiatry ,160, 947–51.
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syndrome. Geriatric Medicine ,13, 297–300.
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antecedents of homicide-suicide and suicide in older married men. The American Journal of Geriatric Psychiatry ,9, 49–57.
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offending and mental disorder. Case linkage study. The British Journal 
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27. Walsh, E., Buchanan, A., and Fahy, T. (2002). Violence and 
schizophrenia: examining the evidence. The British Journal of 
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32. Eronen, M., Hakola, P ., and Tiihonen, J. (1996). Mental disorders and 
homicidal behaviour in Finland. Archives of General Psychiatry ,
53, 497–501.

Dishonesty and deception are mundane and ubiquitous elements 
of human behaviour. Various forms are also categorized as criminal offences in the codes or statutes of all organized societies. In crimi-nological terms, fraud, deception, and theft are forms of stealing, in other words dishonestly depriving others of goods or services. However, deception and fraudulent misrepresentation play a much wider role in human behaviour and interactions. This chapter will ﬁ rst consider brieﬂ  y the broader picture, before considering in 
detail psychiatric aspects of stealing.
Fraud and deception
It is a common tendency to distort memory or reality through the lens of wishful thinking. T o deny, to lie to others, and to engage in self-deception is part of the human condition. At one level, this can

amount to innocuous forms of self-distraction, such as daydream-ing or the childhood world of make-belief. Both blend the borders between fantasy and reality. Deception, which more bluntly put means lying, is on the other hand instrumental in purpose. The essential elements of lying are a conscious awareness of falsity, the intent to deceive and a pre-conceived goal or purpose. In some walks of life, such as advertising or politics, it may be part of the job, at least when the individual thinks that they can get away with it. Deception of others may slide into self-deception, the editing of memory to suit current desires. This may concern a wide range of life’s extravagancies, from the fraudulent endeavours of the narcis-
sistic fantasist to the imperatives of those who convince themselves, 
or wish to convince others, of their own supposed illnesses or inﬁ  r-

mities. Particular forms of fraud, deception, and self-deception relevant to the medical context are factitious disorder, malingering, and pathological lying: these are dealt with in Chapter 5.2.9.
Theft
Types
Categorization of offences differs between jurisdictions. However, that for England and Wales forms a basic, illustrative framework. Offences are categorized under the Theft Act 1968 into theft, bur-glary, vehicle offences, and deception. The Theft Act 1978 further clariﬁ  es the area of deception (dishonestly obtaining services from another), dividing it into evading liabilities and debts, and making 
off without payment. The Fraud Act 2006 provides for a general offence of fraud with three ways in which it can be committed—by false representation, by failing to disclose information, and by abuse of position.
Rates/prevalence

Rates of criminal theft, fraud, and deception can be examined in terms of offences committed per unit of population. In England and Wales, with a population of 53.3 million, the number of report-ed fraud, theft, and deception offences in 2006 was 2 789 600, which equates to approxi mately 5.2 per 1 000 total population. These comprised 51 per cent of all crimes reported to the police.
(1)
However, crime is under-reported to the police and it is notable that the rate of offending as recorded by population survey in England and Wales is generally more than double. International comparisons of crime ﬁ  gures are hampered by differences in classiﬁ  -
cation, measures, and time period.
A motivational classiﬁ  cation of theft
Theft and dishonesty may arise from a range of motives. There is

Theft and dishonesty may arise from a range of motives. There is 
no necessity to invoke mental disorder in order to explain thieving. However, a minority of cases are related to serious mental disorder, such as mania, schizophrenia, depression, and organic brain dis-order; and other forms of abnormal psychological processes can act as drivers for criminally dishonest behaviour. These go beyond the formal classiﬁ  cation of such behaviours in, for instance, the 
DSM-IV-TR,
(2) where these appear only in the speciﬁ  c syndrome 
of kleptomania and as a component of the deﬁ  nitions of conduct 
disorder and anti-social personality disorder.
The following classiﬁ  cation is not exhaustive and the categories 
not mutually exclusive. The great majority of thefts will ﬁ  t into the 
ﬁ rst two categories, and it is the remainder that are more likely to 
form part of a presentation to a psychiatrist.
(a) Ordinary theft

Ordinary theft may be planned or impulsive, but is deliberate and motivated by the usefulness of the object or its monetary value.
1 Professional—crime as a career choice.2 Delinquent—theft as one component of a delinquent or anti-
social lifestyle.Fraud, deception, and thieves
David V. James11.6

SECTION 11  forensic psychiatry 1942
3 Survival offences—driven by poverty, desperation, or necessity.
(b) Emotionally driven theft
Emotionally driven theft is the consequence of emotion, rather 
than as a means of ﬁ  nancial gain.
 4 Anger or revenge—based upon depriving someone else, rather 
than personally acquiring.
 5 Fear—coerced into committing an offence by threats from a 
third party.
 6 Excitement—this can be as part of a dare or a rite of passage, 
particularly in adolescents.
(c) Secondary theft
Secondary theft is attributable to the presence of an underlying disorder.
(i) Pecuniary
 7 T o fund addictive behaviour—e.g. alcohol dependence, drug 
addiction, pathological gambling.
(ii) Non-pecuniary
 8 Depressed stealing:
(a) cry for help (attention-seeking behaviour): stealing in a way 
that is sure to be detected in order to obtain support and other help.
(b) suicidal gesture: a depressed persons may steal articles of

(b) suicidal gesture: a depressed persons may steal articles of 
which they have no need, the action serving as a justiﬁ  ca-
tion for feelings of guilt and a form of suicidal equivalent.
(c) substitution: the stolen object compensates for something 
else. For example a rejected wife might steal from her hus-band in order symbolically to establish a degree of control and compensate for the loss of affection.
(d) distraction: e.g. ‘absent-mindedness’ in a shop as a conse-
quence of distraction by depressive ruminations, or distress 
in the context of bereavement or divorce.
 9 Manic stealing: stealing in the context of manic disinhibition or 
delusion.
10 Psychotic: the result of delusional drive or command 
hallucinations.
11 Confusion: related to cognitive deﬁ  cit, as a consequence of 
organic brain disorder, or to dissociative states.
12 ‘Kleptomania’: compulsive stealing as an impulse-control 
disorder.

disorder.
A psychiatrist will only have a role in the management of theft cases where a particular psychiatric or psychological issue is central. The management will depend upon the nature of the underlying disorder. Treatment for the primary disorder will, in most cases, be supplemented by a psychological approach to help-ing the patient understand the reasons for their offending behav-iour, recognize triggers or danger points, and develop strategies for dealing with these in the future.
Kleptomania constitutes a particular diagnostic entity, and shop-
lifting is a common behaviour which not uncommonly leads to requests for psychiatric reports from the courts. Both will be considered in more detail below.Kleptomania
Deﬁ nition
Kleptomania is an old term, ﬁ  rst used by Marc and Esquirol in 1838

Deﬁ nition
Kleptomania is an old term, ﬁ  rst used by Marc and Esquirol in 1838 
to indicate a ‘stealing madness’ . Kleptomania was designated a psychiatric disorder in DSM-III in 1980, and, in DSM-IIIR in 1987, it was grouped under the category ‘impulse control disorder, not elsewhere classified’ . The disorder is described further in Chapter 4.13.1 (Impulse Control Disorders) and only aspects most relevant to forensic practice are considered here.
The core characteristic is that objects are stolen despite the 
fact that they are typically of little value to the individual, who could have afforded to pay for them. Sometimes, they are hoarded and sometimes dispensed with or returned. DSM-IV-TR describes the essential features of the disorder in ﬁ  ve diagnostic criteria 
(312.33):
(a) ‘Recurrent failure to resist impulses to steal objects that are not 
needed for personal use or for their monetary value.
(b) Increasing sense of tension immediately before committing the 
theft.

theft.
(c) Pleasure, gratiﬁ  cation, or relief at the time of committing the 
theft.
(d) The stealing is not committed to express anger or revenge and 
is not in response to a delusion or a hallucination.
(e) The stealing is not better accounted for by conduct disorder, a 
manic episode, or anti-social personality disorder’ .
In addition, individuals with kleptomania ‘experience the 
impulse to steal as ego-dystonic and are aware that the act is wrong and senseless’ .

Criterion A, which concerns the senselessness of the theft, is often considered to be the characteristic which separates kleptomania from ordinary theft. However, some kleptomaniacs may desire the items and be able to use them, even if they are not strictly needed: this may be particularly the case with those who hoard.
(3) Concerning 
criteria B and C, some patients report amnesia surrounding the time of the theft and therefore deny feelings or tension immediately beforehand or relief at the time of committing the theft.
(3,4) There is 
also some suggestion that kleptomaniacs who repeatedly steal over 
long periods eventually lose the feelings of tension and pleasure in a behaviour which has simply become a habit.
There may be overlap with other disorders.
(5) Kleptomania and

(5) Kleptomania and 
drug addiction share similar core qualities.(6) The presence of 
repetitive thoughts and behaviours suggests to some a link with the obsessive-compulsive spectrum.
(7) With the high comorbidity with 
depressive disorders, kleptomania might be categorized within the affective spectrum.
(8)
The prevalence of kleptomania is unknown though it is thought to account for less than 5 per cent of shoplifting.
(2) In the US the 
lifetime prevalence may be 0.6 per cent(3) though some consider 
that it may be higher because the associated embarrassment and illegality may deter people from reporting it.
(9)
A US study of psychiatric inpatients found a lifetime preval-
ence of 9.3 per cent.(10) While of 107 inpatients with depression,

1943
3.7 per cent had kleptomania(11) and, of 79 inpatients with 
alcohol dependence, 3.8 per cent reported symptoms consistent with kleptomania.
(12)
Kleptomania was generally believed to be much more common 
in women, but in a summation of four studies of kleptomania 63 per cent were women,
(5) suggesting that the preponderance of 
women is not as great as was once assumed.
Kleptomania is highly comorbid with depression and anxiety.(13–15)
Estimates of lifetime comorbid rates of mood disorders range from 59
(9) to 100 per cent,(16) and of anxiety disorders from 60 to 
80 per cent.(17) Some of the comorbidity with depression and anxi-
ety may be secondary to the consequences of the behaviour. Compared with people with alcohol dependence and general psy-chiatric disorders, those with kleptomania scored signiﬁ  cantly 
higher on measures of impulsivity, sensation-seeking, and disinhi-bition.
(14) In one study,(18) 43 per cent of people with kleptomania

(14) In one study,(18) 43 per cent of people with kleptomania 
met the criteria for at least one personality disorder, the most common being paranoid, schizoid, and borderline. However in a meta-analysis none satisﬁ  ed the diagnostic criteria for anti-social 
personality disorder.
(19)
Aetiology
The aetiology of kleptomania is uncertain. Suggested causes include attempts to relieve feelings of depression through stimulation,
(20,21)
or to make up for early deprivation.(5,22) The various theories are 
considered further in Chapter 4.13.1
Treatment

(20,21)
Treatment
Treatment involves a combined psychological and pharmacological approach. There is little evidence to suggest one particular psycho-logical approach, but a combination of cognitive behaviour therapy and psychosocial interventions is generally adopted. As regards drug treatments, there have been case reports and small series sug-gesting the efﬁ  cacy of a range of drugs,
(23) in particular selective 
serotonin re-uptake inhibitors, mood stabilizers, and opioid antagonists. However, there is a need for controlled trials before deﬁ nitive conclusions can be drawn.
Shoplifting
Shops specialize in making items seem desirable and tempting 
to the shopper. Most people shoplift at least once at some point in their lives, usually opportunistically in adolescence. But the inci-dence of shoplifting remains unknown. An early observational study in the UK

(24) suggested that 1 to 2 per cent of customers in an 
English department stores took items without paying, which compared with 1 in 12 in New Y ork City and 1 in 18 in Dublin. The number of people convicted of shoplifting is evidently far smaller. Whereas earlier studies had suggested that shoplifting was more common in women,
(25) this is now thought to have been an arte-
fact of case selection, as samples in most studies have been limited to court samples or sub-samples referred to psychiatrists for reports.
(26)
There is no unitary phenomenon of shoplifting. It has been sug-
gested that those who shoplift fall into two groups—those who do so out of rational choice and those that suffer from depression.
(27)
A survey of 1649 shoplifting convictions in Montréal found that only 3.2 per cent were suffering from serious mental disorder, but that affective symptoms were relatively common.
(28) A further 
study of 106 shoplifters(26) reported that depression was the most

study of 106 shoplifters(26) reported that depression was the most 
common psychiatric disorder associated with shoplifting and that the majority of shoplifters were poor and unemployed. The range of possible psychiatric disorders associated with shoplifting is indicated in the classiﬁ  cation of theft above, but in the large 
majority of cases of shoplifting, there is no psychiatric reason for avoiding payment.
A thorough assessment is needed to order to establish how and why the shoplifting occurred and to indicate the presence or absence of underlying mental illness or disorder. Where such illness or disor-der is present, it should be treated. Where no such factors are in evidence, psychological therapies may still have a role in offender rehabilitation, usually in a group setting.
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Psychiatric Publishing, USA, pp 175–201.
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10. Grant, J.E., Levine, L., Kim, D., et al. (2005). Impulse control disorders 
in adult psychiatric inpatients. The American Journal of Psychiatry ,
162, 2184–8.
11. Lejoyeux, M., Arbaretraz, M., McCloughlin, M., et al. (2002). Impulse 
control disorders and depression. The Journal of Nervous and Mental 
Disease ,190, 310–14.
12. Lejoyeux, M., Feuché, N., Loi, S., et al. (1999). Study of impulse-control 
disorders among alcohol-dependent patients. The Journal of Clinical 
Psychiatry ,60, 302–5.
13. Sarasolo, E., Bergman, B., and T oth, J. (1996). Personality traits 
and psychiatric and somatic morbidity among kleptomaniacs. Acta 
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14. Baylé, F.J., Caci, H., Millet, B., et al. (2003). Psychopathology and 
comorbidity of psychiatric disorders in patients with kleptomania. The
American Journal of Psychiatry ,160, 1509–13.
15. Dannon, P .N., Aizer, A., and Lowengrub, K. (2006). Kleptomania: 
differential diagnosis and treatment modalities. Current Psychiatry 
Reviews ,2, 281–3.
16. McElroy, S.L., Pope, H.G., Hudson, J.I., et al. (1991). Kleptomania: a 
report of 20 cases. The American Journal of Psychiatry ,148, 652–7.
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characteristics and relationship to other psychiatric disorders. The
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18. Grant, J.E. (2004). Co-occurrence of personality disorders in persons 
with kleptomania: a preliminary investigation . The Journal of the 
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19. McElroy, S.L., Hudson, J.I., and Pope, H.G. (1991). Kleptomania: 
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300–2.

Juvenile crime and delinquency represent a signiﬁ  cant social and 
public health concern. Both rates of mental disorders and offend-ing are high during adolescence. This chapter reviews prevalence rates of mental disorders in young offenders, screening, and assess-ment of juveniles, principles of interventions with young offenders before describing principles of forensic mental health, policy and practice, how mental disorders in adolescence can impact on offending and antisocial behaviour, how policy is shaping practice in this ﬁ  eld and how mental health practitioners may be involved 
in meeting mental health needs and undertaking medico-legal assessments
Delinquency, conduct problems, and aggression all refer to 
antisocial behaviours that reﬂ  ect a failure of the individual to con-
form his or her behaviour to the expectations of some authority ﬁ gure, to societal norms, or to respect the rights of other people.

form his or her behaviour to the expectations of some authority ﬁ gure, to societal norms, or to respect the rights of other people. 
The ‘behaviours’ can range from mild conﬂ  icts with authority 
ﬁ gures, to major violation of societal norms, to serious violations 
of the rights of others.
(1) The term ‘delinquency’ implies that the 
acts could result in conviction, although most do not do so. The term ‘juvenile’ usually applies to the age range, extending from a lower age set by age of criminal responsibility to an upper age when a young person can be dealt with in courts for adult crimes. These ages vary between, and indeed within, countries and are not the same for all offences.
(2,3)
Adolescence as a context
The adolescent population in the UK constitutes half of the child population with around 7.5 million young people in the transi-tional stage between childhood and adulthood, (age 10–19).
(4)

(4)
Adolescence is a transitional stage of development between child-hood and adulthood—a stage of possibility and of promises and worries that attend this possibility. The developmental tasks of adolescence centre on autonomy and connection with others, rebellion and the development of independence, development of identity and distinction from and continuity with others. The physical changes of puberty are generally seen as the starting point of adolescence whilst the end is less clearly delineated. Adolescence ends with attainment of  ‘full maturity’ . A range of social and cultural inﬂ  uences including the legal age of majority, may inﬂ  u-
ence the deﬁ  nition of maturity.
(5)Mortality among adolescents, in contrast to almost all other age

(5)Mortality among adolescents, in contrast to almost all other age 
groups, did not fall during the second half of the twentieth century, the main causes being accidents and self-harm.
(4). Health needs 
are greater in this age band than in children in middle childhood (5 to 12 years) or of young adults, and arises out of mainly chronic illness and mental health problems. The main concerns of young people, in relation to health, focus on issues of immediacy that impact on their relations with peers and include problems with skin, weight, appearance, emotions, and sexual health including contraception.
The principal aim of the Y outh Justice System (YJS) is to prevent

The principal aim of the Y outh Justice System (YJS) is to prevent 
offending by children and young people under 18 years of age. There are 157 Y outh Offending T eams in England and Wales. The YJB commissions some 3000 custodial places at any one time for young people under the age of 18 years in 18 Prison Service Y oung Offenders Institutions, 15 Local Authority Secure Children’s Home 
and 4 private sector Secure Training Centres. In 2005–2006 there

and 4 private sector Secure Training Centres. In 2005–2006 there 
were 301,860 recorded offences the 4 highest recorded offences being theft and handling 18.5 per cent, violence against the person 18.1 per cent, motoring offences 16.6 per cent, criminal damage 12.9 per cent. 16 and 17 year old were responsible for 49.6 per cent of offences with males responsible for 80.6 per cent and females 19.4 per cent of all offences resulting in a disposal. Offences by ethnicity were white 85.2 per cent and Black and Ethnic Minority 14.8 per cent. Of the 2 12, 242 disposals 80 per cent received pre-court of ﬁ  rst tier disposals with 17 per cent receiving a community 
sentence and 3 per cent a custodial sentence.
(6)
Risk factors for, and pathways to antisocial behaviour are summa-
rized in Tables 11.7.1 and 11.7.2 respectively. There is a signiﬁ  cant

(6)
rized in Tables 11.7.1 and 11.7.2 respectively. There is a signiﬁ  cant 
overlap between the risk factors for offending, poor mental health and substance misuse and the number of assessed risk factors increas-es as a young person moves further into the Y outh Justice System.
(7)
Many young offenders are not engaged in mainstream education and health services. It is critical that these young people are supported to access the mainstream and specialist services they require while under the supervision of the YOT or in custody. Otherwise, once their sentence ends they can become detached from services and their circumstances are likely to deteriorate, leading to more offend-ing and greater demands on specialist services as they get older.
In the UK, the Children’s National Service Framework for Children,

In the UK, the Children’s National Service Framework for Children, 
Y oung People and Maternity Services (NSF) set out a vision of a comprehensive child and adolescent mental health service.
(8)Juvenile delinquency and 
serious antisocial behaviour
Susan Bailey11.7

SECTION 11  forensic psychiatry 1946
A young person in contact with the criminal justice system, whether 
in custody, or in the community, should have the same access to this comprehensive service as any other child or young person within the general population. Treatment options should not be affected by a young offender’s status within the criminal justice system. The Change for Children Programme has the aim of improving outcomes for all children in the following 5 areas: being healthy, staying safe; enjoying and achieving; making a positive contribution; and achieving economic well-being, and to narrow the gap in outcomes between those who do well and those who do not. If we do not address the mental health needs of young offenders then they are excluded from the opportunity to partici-
pate in improvements in these 5 outcomes and ultimately from the ability to achieve their full potential.
There is a high prevalence of mental health problems among 
young people in custody.

(9) YJB research published in 2005 reported 
the following ﬁ  ndings.(10)
◆ 31 per cent had mental health problems
◆ 18 per cent had problems with depression
◆ 10 per cent suffered from anxiety
◆ 9 per cent reported a history of self-harm in the preceding month
◆ 9 per cent suffered from post-traumatic stress disorder
◆ 7 per cent had problems with hyperactivity
◆ 5 per cent reported psychotic-like symptoms
One in ﬁ  ve young offenders were identiﬁ  ed as having intellectual 
disability IQ <70. Additionally, needs were identified across 
education 48 per cent and social relationships 36 per cent. Needs were unmet because they were not recognized.
Research consistently reveals high levels of psychiatric disorders

Research consistently reveals high levels of psychiatric disorders 
among detained juveniles, although rates vary widely by study, ranging from more than 50 per cent to 100 per cent.
(11–21)  The 
variations between the studies may reﬂ  ect methodological differ-
ences or true variations between countries and samples. Advances in developmental psychopathology and increased understanding of the continuities between child and adult life
(27) demonstrating 
that many childhood disorders once thought to resolve with age cast long shadows over later development.
There are several reasons why high rates of mental disorders 
may be expected in youth in contact with juvenile justice. First, prevalence rates of psychiatric disorders in community samples were shown to be around 15 per cent.
(22) Also, severe delinquency

(22) Also, severe delinquency 
is common in the adolescent population, with about 5 per cent show-ing an early-onset and persistent pattern of antisocial behaviour.
(23)
A substantial number of adolescents will show offending behav-iour and will have a mental health disorder simply because of coincidental overlap between both conditions. Second, because delinquent and antisocial behaviour reaches high levels among juvenile justice populations, a diagnosis of conduct disorder (CD) will often be made. Because CD shows high comorbidity rates with several other psychiatric disorders,
(24) increased levels of many

(24) increased levels of many 
types of disorder may be expected. Third, risk factors for youthful offending overlap substantially with those for several types of non-disruptive child psychiatric disorders, therefore identical risk factors may underlie both antisocial behaviour and emotional or developmental problems. Disorders for which mental health interventions are provided, such as substance use disorders (SUD’s), may also lead to judicial involvement. Also, because of the preva-lence of complex comorbidity, treatment in a regular mental health care programme may be intricate and often is not possible, thus increasing the likelihood of judicial involvement. In addition, severely disordered persons may be less likely to have the personal capability and have adequate resources to defend themselves and to avoid more drastic legal interventions.
Grisso and Zimring listed three principal reasons for concern 
regarding mental disorders in youthful offenders: a) the obligation

regarding mental disorders in youthful offenders: a) the obligation 
to respond to mental health needs in those in custody, b) assurance of due process in adjudicative proceedings, and c) public safety.
(25)Table 11.7.2 Critical pathway to serious antisocial behaviour(64)
Family features
Parental antisocial personality disorder
Violence witnessed
Abuse, neglect, rejection
Personality features
Callous unemotional interpersonal style
Evolution of violent and sadistic fantasyPeople as objects
Morbid identity
Paranoid ideationHostile attribution
Situational features
Repeated loss and rejection in relationships
Threats to self-esteem
Crescendo of hopelessness and helplessnessSocial disinhibition
Group processesChanges in mental state over timeTable 11.7.1 Major risk areas in children and adolescents with 
persistent antisocial behaviour(35)
Broad child-centred factors
Genetic vulnerability
Perinatal riskMale sex

School underachievement
Hyperactivity/inattention temperament
Criminality in parents and siblings
Family discord
Lack of supervisionLack of effective feeling
Abuse
ScapegoatingRejection
Neglect
Inﬂ uential contextual factors
Drug and alcohol abuse
Unemployment
Crime opportunityPeer group interaction

1947
Mental health treatment within the juvenile justice system is 
often inadequate. It has been reported that only about 20 per cent of incarcerated youth with depressive disorders, 10 per cent with other mental disorders, and less than half with SUD receive inter-vention.
(26,27). Much more research is needed into the treatment 
needs of this population.
Risk and protective factors
Understanding is growing of how risk factors combine to both pre-cipitate and maintain antisocial behaviour. Several environmental and individual risk factors including psychiatric pathology in child-hood have been identiﬁ  ed.
(28) Not all risk factors need to be present 
in a single individual but multiple risk factors greatly increases the risk of a serious and long-term negative development.
characteristics or experiences may act protectively. These protective factors may be speciﬁ  c interventions or experienced within the nat-

ural contact of development. When protective factors are present, young people may show positive social development despite high risk of antisocial behaviour, or they may abandon their problem behaviour after a difﬁ  cult phase. Such trajectories are less well 
investigated than the risks.
(30–33) It is also more difﬁ  cult to imple-
ment adequate research designs in this ﬁ  eld.(34) It could be assumed

ment adequate research designs in this ﬁ  eld.(34) It could be assumed 
that the opposite to the risk value of the variables listed in Table 11.7.1 may promote positive development. However, truly protec-tive effects need to compensate for a given high-risk constellation (moderator approach). The available research suggests a number of factors that may protect from the risks of antisocial behaviour. Table 11.7.3 reports a selection of such personal and social resourc-es that have already been proven or may be promising (for a detailed review see
(33)).
Pathways of care and the juvenile 
justice system
Juvenile justice is a high-volume system, which makes clear logis-
tics and a clear pathway of care necessary. Early identiﬁ  cation of

(33)).
tics and a clear pathway of care necessary. Early identiﬁ  cation of 
mental health needs may result in diversion from custody by using community services rather than adjudication and derive economic beneﬁ  t by affording non-custodial disposal. Nonetheless a signiﬁ  -
cant number of young persons progress to pre-trial assessment, albeit from the home or a residential care setting.
Preadjudication dispositions should be informed therefore by 
best available screening and assessment processes. In this context speciﬁ  c tools may be used to derive markers of psychopathology 
and of ongoing risk to self and others as well as to address medico-legal questions posed by the criminal justice system including assessment on disposition, matters of public protection, treatment for mental disorders, and need for security and likelihood of 
recidivism.

For those detained in prison, screening must determine if urgent 
problems (such as suicidal intent or consequences of substance use) require immediate attention; a detailed diagnostic assessment of the young person may take a longer period of time and continue as the youngster moves from one institution to another. Later critical transitions, for which an additional screening may be use-ful, include re-entry into the community, assessment of readiness for re-entry, mental health planning for integrated continuing care post detention as part of a multiagency re-entry strategy, and, where necessary, community residential programmes monitoring 
emotion or reactions, especially where the young person is return-ing to stressful conditions such as a troublesome family.
General principles of assessment
Standard clinical assessment tools used in child and adolescent psychiatry cover many of the areas considered in forensic child and adolescent risk assessments.

(36) This is especially important as 
juvenile justice systems in particular are not always equitable. In choosing between the many scales available it is important to question not just their proven scientiﬁ  c properties but also their 
feasibility for practitioners to use.
It is important to consider the purpose for which the scale is to 
be used (see table below). Scales that measure psychopathology may not be good ways of assessing the risk that the psychopathology poses. Measures used to map out types of symptom must have good content validity. An instrument required to pick out one group of symptomatic people from the rest of the community (e.g. mental health screening of young people in custody) needs to have Table 11.7.3  Multilevel examples for protective factors against

(35)
Biological/bisocial - Non-deviant close relatives; no genetic 
vulnerabilities; high arousal; normal neurological and 
hormonal functioning.
Pre-and perinatal - Non-alcoholic mother; no maternal smoking during 
pregnancy; no birth complications
Child personality - Easy temperament; inhibition; ego-resiliency; 
intelligence; verbal skills; planning for the future; self-control; social problem solving skills; victim 
awareness; secure attachment; feelings of guilt; 
school and work motivation; special interests or hobbies; resistance to drugs
Cognitions/attitudes - Non-hostile attributions; non-aggressive response 
schemes; negative evaluation of aggression; 
self-efﬁ  cacy in prosocial behaviour; non-deviant 
beliefs; realistic self-esteem; sense of coherence.
Family - No poverty; income stability; harmony; acceptance; 
good supervision; consistency; positive role models; continuity of caretaking; no disadvantage; availability 
of social support.

School - Achievement and bonding; low rate of aggressive 
students; climate of acceptance; structure, and supervision.
Peer group - Non-delinquent peers; support from close, prosocial 
friends.
Community - Non-deprived, integrated and non-violent 
neighbourhood; availability of professional help.
Situational - Target hardening; victim assertivesness; social 
control.
Legal - Effective ﬁ  rearm and drug control; effective criminal 
justice interventions.
Cultural - Low violence; tradition of moral values; shame and 
guilt-orientation; low exposure to violence in the media.11.7 juvenile delinquency and serious antisocial behaviour

SECTION 11  forensic psychiatry 1948
good criterion validity. A related issue is the extent to which the 
scale is intended to measure change.
Grid for specifying requirements of 
a structured scale in a juvenile forensic population
Assessment required (yes / no)
Purpose of assessment Psychopathology Need Risk
Screening of all juveniles coming into 
contact with an agency
Detailed assessment e.g. for sentencing, 
planning treatment
Measuring change e.g. during treatment or 
sentence
Child psychiatry uses multi-axial and developmental concepts 
of child psychopathology. Speciﬁ  c and general intellectual delays 
are very common among young people in the juvenile justice system
(10) as is co-morbidity of disorders. Broad-band interviews, 
however, offer only poor coverage of rare conditions such as perva-sive developmental disorders.

Needs assessment may have advantages over more traditional ways of diagnosing disorders, mainly because this method also indicates whether speciﬁ  c conditions need attention and intervention. 
Especially in delinquent youth characterized by mult iple problems, 
such an approach may carry substantial adv antage. A health care 
need should be distinguished from a general need. One commonly used deﬁ  nition of a health care need is ‘ the ability to beneﬁ  t in some 
way from (health) care ’.
(37)
Needs and risk assessment are two separate but intertwined

(37)
Needs and risk assessment are two separate but intertwined 
processes essential for clinical management (see Fig. 11.7.1). Assessment of danger to others and the need to address this problem is at the centre of legislative and policy decision-making. The attention of the public and media are focussed on this area. Needs assessment may both inform and be a response to the risk-assessment process.
(38) The reciprocal process can be termed ‘risk management’ 
when accurate information about the risk assessment, combined with recurrent needs assessment, leads to risk-management proce-dures. A recurrent needs-assessment and risk-assessment process should identify changes in problem areas, thus leading to moni-toring or intervention as part of risk management. Core to this assessment are appropriate me ntal health screening tools and 
processes that are available to the young person at any point in the system.
(39)

(39)
Risk assessment combines statistical data with clinical information in a way that integrates historical variables, current crucial varia-bles, and the contextual or environmental factors. Structured risk assessment instruments have been developed that aim to increase the validity of clinical prediction. These scales typically contain a number of risk items selected from reviews of research, crime theories, and clinical considerations.
(41,42)  Items are summed to 
form a total risk score and may also reveal speciﬁ  c risk patterns 
(e.g. mainly family or child factors). Such instruments are used for screening, in-depth assessment and related risk management (e.g. for decisions on the child’s placement or speciﬁ  c interventions).

They can also be applied in differentiated evaluations of interven-tion programmes. Instruments vary with respect to the age and gender for their clients, problem intensity in the target groups, theoretical and empirical foundations, the number and domains of risk included, scoring procedures, time required for assessment, information sources, institutional contexts of administration and other issues.
(43,44)  Many instruments have been designed for appli-
cation in the juvenile justice system.(43,45,46) Most instruments 
contain factors from various areas of risk (e.g. individual, family, neighbourhood).
Mental disorders and offending
Current concepts focus on a developmental approach to psychopa-thology in child and adolescent psychiatry and psychology. Physical aggression peaks at around the second year of life and subsequently shows distinct developmental trajectories.
(47,48) Attachment enables

(47,48) Attachment enables 
the mastery of aggression, self-control being developed through the efﬁ cient exercise of attritional mechanisms and symbolization. 
Fonagy has suggested a primary developmental role for early attach-ment in the development of mentalization (the capacity to under-stand others’ subjective experience). He suggests that impaired mentalization leads to later violence.
(49) Threats to self-esteem trig-
ger violence in individuals whose self-appraisal is ‘on shaky ground’ and are unable to see behind the threats to what is in the mind of the person threatening them. These processes are played out in the complex and toxic co-morbidities seen so much more frequently in child and adolescent than in adult mental health practice.
Oppositional disorders, conduct disorder, 
and ADHD
Substantially higher rates of physically aggressive behaviour are 
found in children and adolescents with attention deﬁ  cit hyperactivity

and ADHD
found in children and adolescents with attention deﬁ  cit hyperactivity 
disorder, with those who meet the criteria for ADHD and conduct disorder having substantially greater risks of delinquent acts in adolescence, harmful acts in later adolescence and continued vio-lence and offending into adulthood.
(50) Children with hyperactivi-
ty, impulsivity, attention deﬁ  cits and serious conduct problems 
may also be at risk for developing psychopathy.(51)
Distorted or biased thought processes have over time been 
implicated in the development of violence. Psychological treat-ments aimed at reducing violent behaviour in adolescents and young adults traditionally centre on violence as learned behaviour. Patterns of violence and criminal behaviour are seen as embedded in habits of thinking.
(52) In juvenile delinquents signiﬁ  cant cogni-

tive attributional bias has been shown in aggressive children and youths. They are more likely to perceive neutral acts by others as hostile, and more likely to believe conﬂ  icts can be satisfactorily 
resolved by aggression. In the social context, as the young individu-al becomes more disliked and rejected by peers, the opportunity for viewing the world this way increases.
(53) By their late teens 
they can hold highly suspicious attitudes and be quick to perceive disrespect from others. In the social context of juvenile incarceration,

1949
being ‘para’(54) can become in peer group interactions the shared 
norm.(55)
Depression anxiety and post traumatic 
stress disorder in childhood and adolescence
As well as the recognized feelings of low mood in depression there 
is also some evidence of irritability, hostility and anger when depression occurs in adolescence. Irritability in adolescence leads to interpreting annoyances by others as direct threats, increasing the risk of defensive aggression.
(56) Nowhere is this more apparent 
than in juvenile justice populations.(57,58) A self-serving bias with a tendency to attribute good outcomes to the self and bad outcomes 
to external causes observed in ordinary people, is usually regarded as a mechanism for maintaining self-esteem in the face of threats to the self.
PTSD is related to the conditioning of neurobiological fear 
responses underlying tendencies to react aggressively to protect the 
self when exposed to reminders of earlier trauma.
(59) In the recent

(59) In the recent 
escalating context of both children who have experienced violence in war torn countries and those who live in a context of ‘urban war zones’ Garbarino
(60) sets out an ecological framework to 
explain the process and conditions that transform the ‘developmen-tal challenge’ of violence into developmental harm in some children. He set out an accumulation of risk models for understanding how and when children suffer the most adverse consequences of 11.7 juvenile delinquency and serious antisocial behaviour
Population-based
needs assessment
Resources:  quality,
quantity accessibility
type
and screening :
present-based
multiple perspectives
problems, diagnoses,
abilities may be
required
Outcomes
Multiple informants
Quality of life
Symptom change
Offence rate and
typeRisk management
Care programmes Criminal
Justice Sentencing

required
Outcomes
Mental Health Legislation
Childcare LegislationOutcomes
type
Enquiries
HomicidesRisk assessment:
present - and future -
based clinical,
contextual, historical
factorsSystems integration:
communication between
education, health, social
services, criminal justice system
Individual-based
needs/risk
assessment and
screening
Historical and
developmental
information, risk
factorsEpidemiology:  rates or
disorders, problems
Fig. 11.7.1 Relationship between various screening, need assessment, risk assessment, and management approaches in juvenile 
justice systems.(40) (Reproduced from Kroll, L. Needs assessment in adolescent offenders. In Adolescent forensic psychiatry (eds. 
Bailey, S. Dolan, M.), copyright 2004, Hodder Education.)

SECTION 11  forensic psychiatry 1950
exposure to community violence and go beyond their limits of 
resilience, the concept of ‘social maps’ as products of childhood experiences and of trauma as a psychological wound.
The combination of depression, anxiety and severe PTSD is 
being increasingly recognized in as being linked to trajectory into adult anti-social personality disorder.
(61)
Autism spectrum disorders and learning 
Autism spectrum disorders are being increasingly recognized in 
adolescent forensic populations. Their identiﬁ  cation is critical to 
the understanding of violent offending. This is particularly so if an offence or assault is bizarre in nature, the degree or nature of aggression is unaccountable and/or there is a stereotypic pattern of offending. Four reasons have been proposed for offending and aggression in autistic persons:
(62,63)
1 Their social naivety may allow them to be led into criminal acts 
by others;

(62,63)
by others;
2 Aggression may arise from a disruption of routines;3 Antisocial behaviour may stem from a lack of understanding or 
misinterpretation of social cues;
4 Crimes may reﬂ  ect obsessions, especially when these involved 
morbid fascination with violence—there are similarities with the 
intense and obsessional nature of fantasies described in some adult sadists.
(64)
It has been proposed that the paranoia observed in Asperger’s 
syndrome has a different quality from that seen in people with a 
diagnosis of schizophrenia stemming from a confusion of not under-stand ing the subtleties of social interaction and social rules.
(54)
Early onset psychosis
Non-psychotic behavioural disturbance occurs in about half 
of cases of early-onset schizophrenia and can last between 1 and 7 years. It includes externalizing behaviours, attention-deﬁ  cit dis-

order and conduct disorder. This emphasizes the need for mental health assessments repeated over time to include a focus on changes in social functioning (often from an already chaotic baseline level) to a state including perceptual distortion, ideas of reference, and delusional mood.
(65)
As in adult life most young people with schizophrenia are 
non-delinquent and non-violent.(66) Nevertheless, there may be an

increased risk of violence to others when they have active symptoms, especially when there is misuse of drugs or alcohol. The risk of vio-lent acts is related to subjective feelings of tension, ideas of violence, delusional symptoms that incorporate named persons known to the individual, persecutory delusions, fear of imminent attack, feelings of sustained anger and fear, passivity experiences reducing the sense of self-control, and command hallucinations. Protective factors include responding to and compliance with physical and psychoso-cial treatments, good social networks, a valued home environment, no interest in or knowledge of weapons as a means of violence, good insight into the psychiatric illness and any previous violent aggres-sive behaviour and a fear of their own potential for violence. These features require particular attention but the best predictors of future violent offending in young people with mental disorder are the same

as those in the general adolescent population.
(67)Psychopathic personality in young people
A three-factor structure has been proposed,(68) which includes:
◆ An arrogant, deceitful interpersonal style, involving dishonesty, 
manipulation, grandiosity and glibness;
◆Defective emotional experience, involving lack of remorse, poor empathy, shallow emotions, and a lack of responsibility for one’s own actions;
◆Behavioural manifestations of impulsiveness, irresponsibility, and sensation-seeking.
Conduct disorder, antisocial personality disorder, and psy-
chopathy are often seen as developmental disorders that span the life course and the terms are sometimes used interchangea-bly. Conduct disorder and antisocial personality disorder pri-marily focus on behavioural problems, psychopathy, as described by Hare,
(69) emphasizes deficits in affective and interpersonal 
A consensus is likely to be reached only when we have longitudi-

nal studies demonstrating the stability of psychopathic traits over the lifespan and evidence that the same aetiological factors contribute to this disorder at all ages. As there is significant overlap between the behavioural aspects of juvenile psychopathy and ADHD and between the callous-unemotional dimension of psychopathy and autistic-spectrum disorders, future work needs to disentangle these constructs from a phenomenological and aetiological perspective. As yet, there are few treatment out-come studies in juveniles with psychopathic traits, although the limited data suggest that these traits might be a moderator of out-come. Most clinicians view youth psychopathy as a potentially treatable disorder, and there is some evidence that identiﬁ  cation of 
psychopathic traits in young people has a number of beneﬁ  ts, 
which include:

◆Identifying high-risk offenders;
◆Reducing misclassiﬁ  cations that have negative ramiﬁ  cations for 
children and adolescents;
◆Improving and optimizing treatment planning for young people with psychopathic traits, who may require more intensive and risk focused therapeutic approaches.
Interventions with juvenile delinquents
A large number of different treatments have been used to reduce antisocial behaviour. These include psychotherapy, pharmacother-apy, school interventions, residential programmes, and social treatments. Kazdin reported over 230 available psychotherapies, the great majority of which had not been systematically studied.
(70)
This chapter will focus on treatments with a testable scientiﬁ  c basis 
which have been evaluated in randomized trials and applied to populations of young offenders.
(71)
Meta-analyses of treatment approaches to juvenile delinquency

(71)
Meta-analyses of treatment approaches to juvenile delinquency 
have produced reasonably consistent ﬁ  ndings.(72–75) Lipsey(73)
considered nearly 400 group-comparison studies published since 
1950. The main ﬁ  nding was that there was an overall reduction of 
10 per cent in re-offending rates in treatment groups as compared to untreated groups. As might be expected, there were of course considerable variations in the results of individual studies. The best results were obtained from cognitive behavioural, skills-orientated, and multi-modal methods. The results from deterrent trials were

1951
particularly poor, though the numbers in these studies were 
relatively small. Specifically, treatment approaches that were participatory, collaborative and problem-solving were particularly likely to be beneﬁ  cial. Family and parenting interventions also seem 
to reduce the risk of subsequent delinquency among older children and adolescents.
(76)
McGuire and Priestley(52) identiﬁ  ed six principles for effective 
programmes:
1 Intensity should match the extent of the risk posed by the offender.2 A focus on active collaboration, which is not too didactic or 
unstructured.
3 Close integration with the community
4 Emphasis on behavioural or cognitive approaches.
5 Delivered with high quality with training and monitoring of 
staff.
6 Focus on the proximal causes of offending behaviour (peer 
groups, promoting current family communication, and enhanc-ing self-management and problem-solving skills) rather than distal causes (early childhood).

The reviews suggest that there are a number of promising targets 
for treatment programmes, which include antisocial thoughts, antisocial peer associations, promotion of family communication and affection, promotion of family supervision, identiﬁ  cation of 
positive role models, improving problem-solving skills, reducing chemical dependencies, provision of adequate living conditions, and helping the young offender to identify high risk situations for antisocial behaviours. Conversely, the systematic reviews have also suggested a number of approaches that are unlikely to be promising. For instance, improving self-esteem without reducing antisocial cognitions is unlikely to be of value. Similarly, it is unlikely that a focus on emotional symptoms that is not clearly linked to criminal conduct will be of great beneﬁ  t.

Life experiences associated with treatment ressistance are sum-
marized in table 11.7.4.
Promising interventions for adolescent 
antisocial behaviour
A rational starting point when considering interventions would be 
to consider the main causal factors and processes (see above), and design interventions around them. However, in practice many 
other considerations have shaped interventions, from the desire to punish offending youths, to making use of what is currently avail-able at relatively low cost. For generic interventions for conduct disorder also highly relevant to juvenile delinquency and serious antisocial behaviour (see Chapter 9.2.5).
Working with young offenders with mental 
health problems—some practice points for interventions
Interventions with juvenile offenders, regardless of whether 
they are addressing offending behaviour or mental health problems, should take into account developmental and cognitive factors signiﬁ  cant to this age group. Interventions designed for

they are addressing offending behaviour or mental health problems, should take into account developmental and cognitive factors signiﬁ  cant to this age group. Interventions designed for 
use with adults are usually highly structured and target driven. This style of intervention is often perceived by juvenile offenders as alienating and not relevant to their lives with the result that they are likely to disengage (either actively or passively) from the programme.
The skills required to engage a juvenile offender in a ‘therapeutic 
alliance’ are often different to those necessary with adult offenders. Adult offenders are more likely to see the value of participating in an enhanced thinking skills course, possibly as a means to an early release or to improve the quality of relationships within their family unit. Such goals may be perceived as too long range to have 
any meaning to a juvenile offender, or simply seem irrelevant.

any meaning to a juvenile offender, or simply seem irrelevant. 
Juvenile offender’s general experience of relationships with adults, particularly professionals, is of authority ﬁ  gures that give instruc-
tions, set limits on behaviour, and at best are givers of information. The typical responses to this are to adopt an aggressive posture or one of passive indifference. T o actively engage with juvenile offend-ers professionals need to listen attentively and show interest in the young person’s perspective. This does not mean agreeing with the young person’s point of view; however, it is an opportunity to establish the ‘middle ground’ within which a therapeutic alliance may be fostered.
Adolescent offenders have often experienced unstable lives 
with disrupted attachments. Thus they often have difﬁ  culty in 
understanding the signiﬁ  cance of life events such as trauma and

understanding the signiﬁ  cance of life events such as trauma and 
bereavement that an adult will readily understand is likely to impact on emotional well being. A thorough assessment prior to com-mencing an intervention and drawing on material from multiple sources, particularly parents or professionals who have a detailed knowledge of the young person, is very helpful. Events such as the loss of a parent and the onset of conduct problems are often closely linked temporally, yet young offenders frequently do not see any connection between such events.
A formulation is a brief statement that summarizes the possible 
links between different aspects of the young person’s life, for instance between a bereavement and the onset of behavioural difﬁ culties. Juvenile offenders are often unable to make formula-

tions because of their failure to understand how different elements 
of their lives are connected. The ability to make formulations can 
be seen as a developmental milestone and adolescent offenders, for the reasons identiﬁ  ed above, often lag behind their own peer 
group as well as the adult population. Regardless of whether addressing offending behaviours or mental health problems, professionals working with juvenile offenders need to generate Table 11.7.4 Life experiences associated with treatment resistance
Early modelling experiences
Early exposure to related phenomena
Enduring antisocial behaviours and aggressive response patterns
Limited judgement skillsLow academic achievement
Clusters of confrontative acts
Personality traits of callousnessJealousy and revenge

Limited parental/carer supervision
Erratic punishment schedules
Absent, neglecting, or abusive parenting
Parental psychopathology
Reproduced from Losel F, Bender D, Protective factors and resilience. In (eds. Farrington 
DP , Cold JW) Prevention of Adult antisocial behaviour, p. 130–204. copyright 2003, with permission of Cambridge University Press.11.7 juvenile delinquency and serious antisocial behaviour

SECTION 11  forensic psychiatry 1952
such formulations collaboratively so that they make sense both 
within the therapeutic framework and also within the young person’s life experience.
Establishing therapeutic goals also needs to be collaborative and

Establishing therapeutic goals also needs to be collaborative and 
developmentally appropriate. Adolescence in general is character-ized as a time of heightened emotional responses (partly as a result of hormonal changes), a growing but still limited capacity for problem solving and the tendency to seek immediate advantage rather than long-term gain. All of these factors are likely to be enhanced in juvenile offenders in contrast with the rest of their peer group. Goal setting therefore needs to concentrate heavily on the short-term, i.e. within the young person’s perceived time frame. Targets and rewards should be low key in order to reduce the likelihood of extreme emotional responses to success or failure. Therapists working with juvenile offenders need to be active in encouraging the generation of alternative solutions in order to extend the young persons range of problem solving skills.

Juvenile offenders’ capacity to generate alternative strategies is 
often limited by their own, limited emotional range. They will typically respond to any adverse event with hostility and anger; events that would typically evoke a response of sadness or fear within adults. Work on emotional recognition with juvenile offenders will assist them in recognizing a wider range of emotions, both in themselves and others. This enhances their range of options 
when faced with future adverse events.
There is often a tendency to concentrate on behavioural objec-
tives as the most easily recognized or measured outcomes. However, working on goals such as recognizing and managing arousal levels, or shifting cognitions or attributions in speciﬁ  c situations may 
prove more beneﬁ  cial in the longer term even if immediate behav-
ioural changes are not achieved.
Goal setting and intervention strategies should be individually

Goal setting and intervention strategies should be individually 
tailored and take into account differences in cognitive ability, maturity and insight within this population. T o ensure the young person remains actively engaged in the intervention process it is important to frequently check out the ir perception of how effective 
the therapy is, and whether the goals and strategies are relevant. Therapists should frequently check the young person’s level of understanding to ensure that the communication is two way and repeats elements or themes as necessary to ensure good compliance and comprehension, rather than adhering to a timetable.
Treatment and special crimes
Juvenile homicide
Violent behaviour often involves a loss of sense of personal identity and of personal value. A young person may engage in actions without concern for future consequences or past commitments.

Violence denotes the ‘forceful inﬂ  iction of physical injury’ .
(77)
Aggression involves harmful, threatening or antagonistic behav-
iour.(78) Longitudinal studies are invaluable in mapping out the 
range of factors and processes that contribute to the development of aggressive behaviour and in showing how they are causally related.
(79) However, in attempting to work with any individual 
who has committed a violent act, the question to be answered is ‘why this individual has behaved in this unique fashion on this occasion’ .
(73)
Studies show that children and adolescents who murder share 
a constellation of psychological, cognitive, neuropsychiatric, educational and family system disturbance.(80–82) In the UK, young

(73)
a constellation of psychological, cognitive, neuropsychiatric, educational and family system disturbance.(80–82) In the UK, young 
people who commit grave sadistic crimes including juvenile homi-cide are liable to periods of lengthy incarceration. Detention itself can provide time for further neuro-developmental, cognitive, and emotional growth. Irrespective of treatment models, the provisions of education, vocational training, consistent role models and con-tinued family contact are of critical importance.
The approach to juvenile delinquency, including juvenile homi-
cide, in the Netherlands is determined by a policy of minimal inter-vention, with a strongly pedagogical point of view. The emphasis lies on education and treatment rather than on punishment. Cases recorded by the police as murder or manslaughter in the ﬁ  rst

instance may not ultimately be presented to court as such. Moreover, the pedagogical nature of the punishments is recognizable in the fact that treatment is ordered in most cases, in the form of place-ment in a juvenile institution, sometimes in combination with imprisonment, rather than a straightforward youth detention or imprisonment. There are no indications of special policies for prosecuting or handling the cases of legal minors suspected of murder or manslaughter. The limited prevalence of this phenome-non is undoubtedly partly due to the fact that every case is judged on its own merits. Incidentally, this is also noted in the USA where a considerably higher number of youths are sentenced for murder and manslaughter.
(83)
Y ouths who have been prosecuted for murder or manslaughter

(83)
Y ouths who have been prosecuted for murder or manslaughter 
vary only slightly or not al all from other juvenile delinquents on points such as age, gender and ethnic background, and only to a limited extent on risk factors. Murder and manslaughter are com-mitted alone comparatively more often, and on average the perpe-trators start their criminal activities at a later age and are much less likely to have previous convictions than other minors taken into judicial youth institutions. At the same time, it is clear that while the group of youths involved in murder and manslaughter may be small, it is anything but homogeneous. There is great variety in terms of motives, victims, modus operandi etc. In simple terms each case stands on its own.
The majority of young persons who have killed initially dissociate 
themselves from the reality of their act, but gradually experience a progression of reactions and feelings akin to a grief reaction.

The young person whilst facing a still adversarial, and public pre-
trial and trial process has to move safely through the process of disbelief, denial, loss, grief and anger/blame. Post traumatic stress disorder arising from the participation in the sadistic act (either directly or observing the actions of co-defendants) has to be treat-ed, as does trauma arising from their own past personal emotional, physical and/or sexual abuse.
A combination of verbal and non-verbal therapies are effective 
but qualities such as previous frequent and severe aggression, low intelligence and a poor capacity for insight weigh against a safe outcome.
(84) In understanding the role of violence and sadism

(84) In understanding the role of violence and sadism 
in a young person’s life one has to understand the depth of their sensitivity and reaction to perceived threat and their past maladap-tive behaviours aimed at allowing them to feel in control of their lives. In coming to terms with their internal rage, addressing victim empathy saying sorry and reattribution of blame, expression of anger and distress within sessions is expected and is often sexual-ized in both form and content. This can spill outside sessions when the young person and carers can become collusively dismissive and rejecting of therapists,
(85) emphazing the importance of intensive

1953
work to prepare the young person for transition from long term 
incarceration and re-entry into the community together with extended aftercare.
Sexually abusive behaviour
Sexually inappropriate behaviour in children and adolescents con-stitutes a substantial health and social problem.
(86) Most, but not 
all, abusers are male, often come from disadvantaged backgrounds with a history of victimization, and sexual and physical abuse
(87)
and show high rates of psychopathology.(88) Of particular concern 
are a signiﬁ  cant subgroup with mild intellectual disability whose 
treatment programmes have to be tailored to their level of develop-ment and cognitive ability. Y oung abusers come within the Criminal Justice System but also should be considered in their own right within the child protection framework. Most adult sexual abusers of children started their abuse when adolescents and yet neither ICD10 nor DSMIV has a diagnostic category for paedophilia in those under 16.

A structured carefully planned multi-agency approach is required 
when working with sexually aggressive younger children and sexu-ally abusive adolescents. The three stages to assessment of juvenile sexual offenders are:
1  Clariﬁ  cation and rapport building
2 Mapping the abuse: the fantasies, strategies and behaviours; and3 The future, placement treatment and personal change.
The treatment process occurs in the context of:
◆ The crisis of disclosure;
◆ Family assessment;
◆ Therapeutic work in a protective context for the victim; and
◆ Reconstruction and reuniﬁ  cation of the family.
The ‘family’ in this context may include foster carers, or long 
term residential carers.
Treatment outcome

The earliest possible interventions with young over-sexualized children, before their patterns of sexually aggressive behaviours become entrenched, are likely to be most effective. However, there is a dearth of longitudinal follow-up studies looking at treatment outcomes with this younger group of children.
Outcomes may be measured by looking at recidivism, treatment 
outcome or other measures. At present, there are no longitudinal outcome studies of children and adolescents with sexually abusive behaviour which have measured other outcomes such as adult adjustment, attitudinal change or parenting.
Recidivism as a sole outcome measures for treatment is unlikely

Recidivism as a sole outcome measures for treatment is unlikely 
to be reliable since persistent sexual behaviour problems in children under the age of criminal responsibility will not appear in crime statistics and conviction statistics for sex offenders of all ages are 
notoriously unreliable for a variety of reasons including failure to 
report victimization experiences, failure to proceed with charges and a high rate of trial failures.
Other factors appear to be highly relevant to treatment outcomes 
with juvenile sexual abusers such as good interprofessional communication and a systemic context for treatment to occur.New approaches to CBT with sexually abusing youths have 
recently been described within the context of relapse prevention and a more complex CBT intervention, Mode Deactivation Therapy (MDT), has been suggested for disturbed, sexually abusive young people with reactive conduct disorders or personality disorders
(89)

(89)
CBT group work with sexually abusing children and young people is widely practised in the UK and the principles of this work are described by Print and O’Callaghan.
(90)
Other treatment approaches will take into account the living 
context of the young person and the need for his or her carers to be provided with support and explanation of the treatment process in order to maximize positive results. For instance, when children and young people who sexually abuse are still living at home or in con-tact with their parents, family work is usually needed. An approach to group work with parents of children with sexually abusive behaviour has been described.
(91) In the case of children and young 
people who are living in the care system, concurrent work for the professionals and carers looking after the sexually abusing child or young person has been strongly advocated.
There are a signiﬁ  cant number of mid-adolescent, recidivist,

There are a signiﬁ  cant number of mid-adolescent, recidivist, 
delinquent, sexually abusive youths who are too dangerous to other children and young people to be treated (with any treatment modality) alongside other young people. Many of these young people have been through the court system or are currently facing charges. For these reasons, treatment of the sexually abusive young person needs to be undertaken within a close supervized, intensive, community-based foster placement with specially trained foster carers who are experienced in dealing with young offenders, risk and dangerousness. This type of approach is known by various names such as Multidimensional Treatment Foster Care
(92) or forensic foster care.(93) Early results from 
small-scale studies with this type of intervention are reasonably encouraging.
Outcomes claimed for these approaches include signiﬁ  cantly

Outcomes claimed for these approaches include signiﬁ  cantly 
fewer subsequent criminal referrals and more incarcerated boys returning to live with relatives, compared with those who received group home care alone.
(92) In a seven-year study of forensic foster 
care at the Treatment for Appropriate Social Control (TASC), Y okely and Boettner
(93) describe a social responsibility model to 
teach recidivist youths ‘pro-social skills and values that compete with antisocial behaviour’ .
Dynamic psychotherapy aims to work at an unconscious level 
with the sexually abusive young person to explore and understand the reasons for his persistent behaviour. However, evidence-based treatment outcome studies have not yet been undertaken for dynamic therapy with juvenile sexual abusers. A clinical description of long-term dynamic therapy

(94) with these children emphasizes 
the need to establish a systemic child protection context for the safe delivery of such treatment.
In summary, the components of effective treatment interven-
tions with children and young people who sexually abuse will include the following:
◆ A well planned, systemic, child protection orientated, treatment context.
◆ Treatment should be one of a number of positive interventions into the life of the young person and his or her family.
◆ All interventions should be part of an agreed inter-agency care plan for the young person.11.7 juvenile delinquency and serious antisocial behaviour

SECTION 11  forensic psychiatry 1954
◆ Offence-speciﬁ  c interventions, such as CBT, aimed at straighten-
ing out the distorted cognitions and self-justiﬁ  cations of sexually 
abusing young people should be the core of any intervention programme for this client group.
◆Treatment programmes not focussed solely on the victimization of the young person.
◆Interventions should occur at all possible levels including indi-vidual work with young person, family work (where relevant), support for foster carers or for professional care staff and consul-tation to the professional network.
Firesetting/arson
Arson can have a devastating impact on the victim and the wider society. Juvenile arsonists are not a homogenous group, with a wide range of familial,
(95) social,(96) developmental interpersonal,(97)
clinical and ‘legal’ needs. Kolko and Kazdin(98) highlighted the 
importance of attraction to ﬁ  re, heightened arousal, impulsivity

importance of attraction to ﬁ  re, heightened arousal, impulsivity 
and limited social competence. As with other forms of serious antisocial behaviours, no single standard treatment approach will be appropriate for all individuals.
(99) In addition to the general 
assessment of antisocial behaviour the speciﬁ  c domains to be 
considered include:
◆ history of ﬁ  replay;
◆ history of hoax telephone calls;
◆ social context of ﬁ  resetting (whether alone or with peers);
◆ where the ﬁ  res were set;
◆ previous threats/targets;
◆ type of ﬁ  re, single/multiple seats of ﬁ  re setting;
◆ motivation (anger resolution, boredom, rejection, cry for help, 
thrill seeking, ﬁ  re ﬁ ghting, crime concealment, no motivation, 
curiosity, and peer pressure).
For recidivistic ﬁ  resetters therapy may include:
◆ Psychotherapy to increase the understanding of the behaviour,

◆ Psychotherapy to increase the understanding of the behaviour, 
including antecedents deﬁ  ning the problem behaviour, and 
establishing the behavioural reinforcers;
◆ Skills training—to promote adaptive coping mechanisms;
◆ Understanding environmental factors to manage or self trigger solutions;
◆ Counselling to reduce psychological distress;
◆ Behavioural techniques to extinguish the behaviour;
◆ Education to promote understanding of cause and effect; and
◆ Supervision for the staff caring for the adolescent.
Early modelling experiences and early exposure to related 
phenomena militate against a good outcome.
The role of specialist child and adolescent 
mental health services in medico–legal assessment
In the case of T&V v United Kingdom(100) it was stated that a child’s 
age, level of maturity and intellectual and emotional capacities must be taken into account when they are charged with a criminal

age, level of maturity and intellectual and emotional capacities must be taken into account when they are charged with a criminal 
offence and that appropriate steps should be taken in order to pro-mote their ability to understand and participate in the court pro-ceedings. A responsibility therefore falls on the defence lawyer to be aware of the possibility that a young person may not be able to participate effectively in the trial process, particularly if they are under 14 years old or have learning problems, or a history of absence from school.
(101) In 1985, the Office of the High 
Commissioner for Human Rights, in reference to the age of crimi-nal responsibility stated that there is a close relationship between the notion of responsibility for delinquent or criminal behaviour and other social rights and responsibilities.
All young defendants, regardless of the offences they charged

All young defendants, regardless of the offences they charged 
with, should be tried in youth courts with permission for adult sanctions for older youths if certain conditions are met. This should enable a mode of trial for young defendants to be subject to safeguards that can enhance understanding and participation. Assessment of cognitive and emotional capacities should occur before any decisions on venue and mode of trial take place.
Capacity

Capacity
One fundamental distinction in the criminal law is between condi-tions that negate criminal liability and those that might mitigate the punishment deserved under particular circumstances. Very young children and the profoundly mentally ill may lack the minimum capacity necessary to justify punishment. Those exhibit-ing less profound impairments of the same kind may qualify for a lesser level of deserved punishment even though they may meet the minimum conditions for some punishment. Immaturity, like mental disorder, can serve both as an excuse and as mitigation in the determination of just punishment. Capacity is sometimes thought of as a generic skill that a person either has or lacks. However, that is not so. T o begin with, it is multifaceted, with four key elements. These are as follows:
1 The capacity to understand information relevant to the speciﬁ  c 
decision at issue (understanding).
2 The capacity to appreciate one’s situation as the defendant is

2 The capacity to appreciate one’s situation as the defendant is 
confronted with a speciﬁ  c legal decision (appreciation).
3 The capacity to think rationally about alternative course of action 
(reasoning).
4 The capacity to express a choice among alternatives.
(102)
The second key point is that capacity is a feature that is both situ-
ation-speciﬁ  c and open to inﬂ  uence.
Any evaluation of competence should include assessment of 
possibly relevant psychopathology, emotional understanding as well cognitive level, the child’s experiences and appreciation of situations comparable to the one relevant to the crime and to the trial, and any particular features that may be pertinent in this indi-vidual and this set of circumstances.
(103) The general principles to

(103) The general principles to 
be used in the assessment are broadly comparable to those employed in any clinical evaluation. However, particular attention needs to be paid to developmental background, emotional and cognitive maturity, trauma, exposure and substance misuse. The likely appro-priate sources for obtaining clinical data relevant to assessment of a juvenile’s competence to stand trial will include a var iety of historical
records, a range of interviews and other observations and in some cases, specialized tests. Records of the child’s school functioning,

1955
past clinical assessment, treatment history and previous legal 
involvements need to be obtained. In coming to an overall formu-lation, there should be a particular focus on how both develop-mental and psychopathological features may be relevant to the forensic issues that have to be addressed.
The main focus is on the youth’s ability to understand and cope 
with the legal process. This comes from three sources, direct ques-tioning of the defendant, inferences from the functioning in other areas and direct observation of the defendant’s behaviour and interaction with others. It is useful to enquire about the youth’s expectations about what the consequences of the court involve-ment might prove to be. Because of the course of juvenile proceed-ings can vary so widely, with consequences ranging from the extremely aversive to extremely beneﬁ  cial, rational understanding

will necessarily involve a high degree of uncertainty. Potentially relevant problems include: inattention, depression, disorganization of thought processes that interfered with the ability to consider alternatives; hopelessness, such that the decision is felt not to mat-ter, delusion or other ﬁ  xed beliefs that distort understanding of 
options (or their likely outcomes), maturity of judgement and the developmental challenges of adolescence.
In providing information to the court, written reports have the 
advantage of a standard format that helps the consultant to be sure that s/he has considered all the relevant questions; it also provides a familiar structure for readers. In essence, for the sake of consistency and clarity, competence reports need to cover the following areas:
1 Identifying information and referral questions.2 The description of the structure of the evaluation including 
sources and a notation of the conﬁ  dentiality expectations.

3 The provision of clinical and forensic data.
Grisso
(104) suggested that psychiatric assessment of competence 
in young people should include assessment of:
◆ understanding of the charges and the potential consequences
◆ understanding of the trial process
◆ capacity to communicate with their defence lawyer
◆ general ability to participate in the courtroom proceedings.
In court, a child’s ability to give an account of events can be 
impaired by a number of factors, including poor physical health on the day of the trial, overwhelming anxiety or anger about giving evidence, or intimidation by the physical surroundings of the court. From a psychological perspective, however, the basic eviden-tial capacity of the child defendant will depend on two main components:

◆The child’s mental state—this needs to be stable, therefore any disturbance that might interfere with the child’s perception of the world and the ability to understand it will impair evidential capacity;
◆The child’s cognitive ability—a concept that includes a large number of facets, such as memory, understanding and the ability to communicate. The last includes both verbal (speech) and non-verbal means, as well as the ability both to comprehend and to express thought. Any psychological assessment therefore has to be across a range of domains.
Discrepancies are particularly likely in the areas of educational 
achievement, adaptive skills and social and emotional development. A child’s ability often is gauged on educational achievement and

achievement, adaptive skills and social and emotional development. A child’s ability often is gauged on educational achievement and 
given as being equivalent to that of a certain age—e.g. a 15-year-old child might have the everyday living skills of a 7-year-old. However, a child who might be unable to cope with monetary change or public transport might well have the emotional and social experiences of an older child and the drives of an adolescent.
When discussing developmental psychology and child develop-

ment, it is important to bear in mind that none of these processes operates in a vacuum. The child’s experience of parenting (impor-tant in relation to physical and emotional development), the provision of appropriate role models (moral development and self-control depend heavily on appropriate modelling and social learning) and the learning environment (whether it fostered or hindered intellectual development) all have a vital role. For instance, during adolescence, as young people take on a wider and more social perspective and become integrated within a peer group, they will nevertheless tend to adopt social values and norms (i.e. ideas about ‘right and wrong’) that are very similar to those of their 
parents. Hence, despite any demonstrations of teenage rebellion 
(often short-lived), the majority of adolescents will tend to adopt parental mores, either law-abiding or delinquent.

It should be emphazised that clear-cut ages do not apply to the 
completion of physical, intellectual, emotional, and social develop-ment. For most young people, given appropriate parenting, normal biological development and a structured, emotionally supportive and stimulating environment, the bulk of the aforementioned processes should be achieved by late teenage years and a consider-able degree of intellectual maturation may have occurred by the age of 14 years.
When delivering forensic mental health services for children and

When delivering forensic mental health services for children and 
adolescents it is important that the services are developed in such a way that their needs are met and that the services build on estab-lished concepts of service design in line with a strategic framework. Doing so will require long term planning that actively addresses the requirements of an adequate size and composition of an appro-priately trained, supervized and managed workforce. Such services should be developed with an awareness of the scope of existing services and recognition of current demands, analysing gaps current services.
Adolescent girls
Longitudinal data demonstrates that girlhood aggression contrib-utes to a cascading set of negative outcomes as young women move into adolescence and adulthood.
Y oung girls who engage in disruptive behaviour and ﬁ  ght are at 
risk for:
◆Being rejected by peers
◆Feeling alienated
◆Feeling unsupported in their relationships with peers and adults
◆Struggling academically

risk for:
◆Afﬁ liating with other peers prone to deviant behaviour
◆Becoming involved in more serious antisocial behaviours
◆Choosing antisocial romantic partners
◆Initiating and receiving partner violence11.7 juvenile delinquency and serious antisocial behaviour

SECTION 11  forensic psychiatry 1956
◆Becoming adolescent mothers
◆Having children with more health problems
◆Being less sensitive and responsive as parents
Some are sufficiently antisocial and even violent, they are 
incarcerated, if they are also mothers they may lose custody of their children and opportunities for stable employment and relation-ships are much diminished.
Given low base rates of girls engaging in physical aggression and 
violence, identifying girls at risk is a critically important step for prevention and intervention programmes.
High-risk groups of girls to target include those girls who are 
temperamentally overactive as toddlers and pre-schoolers (fewer than boys) but even more important to target for early identiﬁ  ca-

tion and intervention. Those who have early pubertal development (girls report engaging high levels of bullying as they enter puberty). They may be likely targets as well as perpetrators and sexually abused girls—especially those abused by their biological fathers over a long period of time.
From the available literature interventions to reduce rates of 
aggression, relational aggression and violence in female children 
and adolescents should address the following:
1 Pre-natally delivery of programmes for high-risk expectant 
mothers, (especially young mothers and those themselves aggres-sive or disruptive as children).
2 Augment the parenting skills of at risk young mothers—the

2 Augment the parenting skills of at risk young mothers—the 
evidence show children of young mothers with histories of girl-hood aggression may themselves be more prone to infection and injuries.
(a) Provide additio nal parenting skills around key issues of 
hygiene, child prooﬁ  ng of homes, good nutrition, meal plan-
ning and household management.
(b) Help young mothers to respond optimally to the perceived 
challenging behaviour of their infants and toddlers.
3 Middle childhood, girls episodes of physical aggression are often 
preceded by relational aggression. Interventions to help these girls may include how to:
◆Relate to others
◆Manage strong emotions
◆Understand own aggressive feelings and recognize when own aggression is adaptive in the immediate situation.
◆Understand how ‘girl talk’ ignites hurtful indirect social relational aggression.

◆Understand how relational aggression lead to physical violence for some girls towards peers, adults and partners
The major challenge of altering the trajectories of persistent young offenders has to be met in the context of satisfying public demands for retribution, together with welfare and civil liberties considera-tions. In England and Wales for example we lock up more than 3 000 juveniles at anyone time (age of criminal responsibility set at 10).
Treatment of delinquents in institutional settings has to meet 
the sometimes contradictory need to control young people, to remove their liberty and to maintain good order in the institution, at the same time as offering education and training to foster future prosocial participation in society and meeting their welfare needs.

At least in England and Wales, the legislative overhaul of Y outh Justice
(105) has mandated practitioners to bridge the gap between 
residential and community treatments and to involve families using 
Y outh Offending T eams (YOT’s) to meet this complex mix of needs, but the public demand to remove antisocial youths from the street has led to the implementation of Antisocial Behaviour Orders including children with learning disabilities.
Over the last 30 years there has been a gradual shift in opinion 
regarding effectiveness of intervention with delinquents, from the ‘nothing works’ approach to a ‘what works’ approach. The pressure from politicians and public will remain, for a quick ﬁ  x solution to 
problems that span cultures, countries and generations.
Provision of appropriately designed programmes can signiﬁ  -

cantly reduce recidivism amongst persistent offenders. The mode and style of delivery is important; high quality staff and staff train-ing are required. Community based programmes seem better than institution based programmes. In prison settings, the strongest effects are obtained when programmes are integrated into the insti-tutional regimes.What are the key levers for change?
◆Developing an integrated comprehensive screening and assess-ment tool for mental health, substance misuse and physical health
◆Better identiﬁ  cation of mental health needs by courts with 
effective court diversion.
◆Improving access to child and adolescent mental health services for 16 to 17 year olds across the board.
◆Enhancing the role of health workers in YOT’s.
◆Integrating work of substance misuse workers in custody and YOT’s

◆Enhancing intensive resettlement and aftercare provision—RAP Schemes.
◆Reviewing the demand and need of nationally commissioned adolescent psychiatric secure inpatient beds (88 by 2008).
◆And ensuring all working with young offenders understand and are trained in normal and abnormal child and adolescent development together with awareness of the nature of mental health problems in this stage of the life course and how this impacts on all aspects of a young person’s life.
Our knowledge of true prevalence rates of mental disorders in a 
young offending population is developing further. Child and ado-lescent mental health practitioners have the skills to set the under-standing of delinquency in a developmental context and treat those young offenders with mental disorders. Knowledge is advancing rapidly by an established international research network in Europe and the USA.

Mofﬁ  tt, T.E. and Scott, S. Conduct Disorders of Childhood and Adolescent. 
In Rutter’s Child and Adolescent Psychiatry  (5th edn) (eds. M. Rutter, 
D. Bishop, D. Pine, S. Scott, J. Stevenson, e. Taylor and A. thapar), Chapter 35, pp. 543–54.
Gives a comprehensive review of Conduct disorder classiﬁ  cation, 
prevalence, subtypes, associated co-occurring dsorders and complicating conditions, tackling risk indicators, diagnostic challenges

1957
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In most Western societies sexual offenders are more reviled than 
almost any other type of offender. On both sides of the Atlantic this is reﬂ ected in the sanctions that speciﬁ  cally address this group such as 
Sexually Violent Predator laws in the United States, Dangerous and Long-T erm Offender legislation in Canada, and Sex Offender Orders in the UK. Related approaches include the introduction of sex offender registries and the widespread requirement that children at risk from sexual predators be reported by professionals and others.
The general psychiatrist and the 
sex offender
Though constituting a relatively small proportion of all reported 
offences, sex offending affects large numbers of people in the gen-eral population. Though there are methodological difﬁ  culties 
associated with much of the research in this area, the World Health Organization has reviewed estimates of childhood sexual abuse from 39 countries and found that the prevalence of non-contact,

associated with much of the research in this area, the World Health Organization has reviewed estimates of childhood sexual abuse from 39 countries and found that the prevalence of non-contact, 
contact, and intercourse in female children was about 6, 11, and 4 per cent, respectively; the corresponding ﬁ  gure for males was 
about 2 per cent in all categories.
(1) However, these must represent 
minimal ﬁ  gures as it is known that many victims do not report 
their experience and individual sex offenders, when guaranteed conﬁ  dentiality, will admit to many more offences than they were 
charged with or convicted of.
(2) Various forms of sexual offending 
against adults are also underreported but it has been estimated that about 13 per cent of women and 3 per cent of men have been raped at some time during their lifetime.
(3)
The long-term effects of such victimization has been extensively

(3)
The long-term effects of such victimization has been extensively 
studied and it is clear that people with a history of child sexual abuse, for example, experience a wide range of long-term psycho-logical consequences.
(4)
Although prone to ﬁ  nd reasons to delegate the assessment and 
management of sex offenders to specialized forensic services, the general psychiatrist will ﬁ  nd it impossible to avoid them entirely. 
Minor varieties, such as ‘ﬂ  ashers’ (exhibitionists) or ‘peeping T oms’ 
(voyeurs), may be viewed by the courts as less serious, and the opinion of the generalist will still be appreciated, especially when 
specialist resources are scarce and an appointment for a forensic 
assessment could be long-delayed. It is important, therefore, for the general psychiatrist to have some understanding of this area in 
order to make appropriate decisions and recommendations.
Deﬁ nitions of sexual offending
Put simply, a sexual offender is an individual whose sexual behav-

iour contravenes the law in a particular jurisdiction. The types of activities that may be proscribed vary considerably. Western coun-tries are generally more tolerant though most societies provide sanctions for sexual activity involving children below the age of consent, non-consensual sexual acts, sexual relations with close family, and sexual interference with animals or corpses. There are also typically legal and other interventions where a person fears sexual harassment or assault, and where there has been abuse, or likelihood of abuse, in certain professional relationships. Typically, also, there is regulation of pornography or obscene material.
Relationship between sexual deviancy and 
sexual offending
There is some overlap of sexual offences with a medical diagnosis

There is some overlap of sexual offences with a medical diagnosis 
of a paraphilia. However, this is not a complete concurrence. Thus, not all paedophiles have molested a child and not all child molesters are paedophiles; many, perhaps most, men who sexually assault adult women are not sexually deviant or paraphilic at all. The psychi-atric categories of paraphilia and their characteristics are described elsewhere in this volume (Chapter 4.11.3 by Fedoroff).
Types of sexual offender
The vast majority of sexual offenders are male though it is recog-nized that women may also commit similar crimes.
(5) Male sexual 
offenders can be broadly divided into: child molesters, rapists, and non-contact sex offenders.
Child molesters
Typologies of this subgroup in part refer to the degree of paraphilic attraction (sexual deviancy). Thus, there has been a common cate-gorization into ‘ﬁ  xated’ and ‘situational’ or ‘regressed’ types.
(6)

(6)
With the ‘ﬁ  xated’ type there is a permanent attraction to children 
typically dating from adolescence thus conforming to deﬁ  nitions 
of paedophilia in DSM-IV and ICD-10. Those attracted to males are more likely to repeat their offences with recidivism at least Child molesters and 
other sex offenders
Stephen Hucker11.8

1961
twice as high as with those attracted to girls. The former tend to 
victimize boys aged 11–15 years old, whereas the latter molest girls 
of 8 to 10.
‘Fixated’ paedophiles tend to commit premeditated offences that 
often involve considerable planning. Manipulation and ‘grooming’ behaviour is used as a means of luring, even abducting, children into sexual activity, and they may gain the trust of the parents or other carers. They may appear to have an excellent rapport with the child victims and treat them kindly but their motive is primarily for the child to meet their own need for affection rather than the reverse. It is for this reason that ‘needy’ children are often selected as victims. Such offenders will typically profess their ‘love’ for children and convince themselves that their behaviour is not harmful. Other rationalizations, such as that were educating the child or introducing the child to sexual love in a caring way, are common.

‘Regressed’ or ‘situational’ child molesters are, according to this 
typology, attracted primarily to adult females and may be in a mar ital-
type relationship at the time of their offence. They will often report feelings of personal inadequacy or low self-esteem and their offences 
are more typically spontaneous and occur in the context of a stress-
ful life circumstance.
The ‘regressed’ child molester, in contrast to the ‘ﬁ  xated’ type, is 
less inclined to ‘groom’ victims and their caregivers. Victims of this type may be older than those involved with the ‘ﬁ  xated’ molester. 
Molestations however may begin before, and continue past, puberty.
Rapists
Once again, the typology expounded by Prentky, Knight, and col-leagues can be useful.
(6) In this scheme, offenders are differentiated 
through their apparent motivation by anger, power, or sadism. Most rapists act alone but individuals involved in ‘gang’ rape may represent several different types.

‘Anger-motivated’ rapists act out deviant fantasies of retaliation 
towards the victim, using violence as a means of expressing gener-alized anger, typically towards women though sometimes towards people in general. The intention of the attack is to humiliate and debase the victim who will typically have been selected randomly.
The ‘power-motivated’ rapist type has been further subdivided 
into the ‘power-reassurance’ and ‘power-assertive’ types. The for-mer is plagued by doubts and insecurities about their own mascu-linity and sexual adequacy, often uses minimal force and may apologize to the victim or even seek a relationship afterwards. 
However, these victims may have been stalked and the attacks

However, these victims may have been stalked and the attacks 
on them premeditated. The ‘power-assertive’ subtype is motivated by the desire to dominate women and has no doubts about his masculinity but, like the previous subtype, typically does not use gratuitous violence to subdue the victim.
‘Sadistic’ rapists, are the least common but perhaps most worri-
some type, who derive sexual pleasure from inﬂ  icting hurt and 
suffering on their victim. Sometimes, however, this is difﬁ  cult to 
differentiate from other types where pain, suffering and humilia-tion are the consequences, but not the primary motivation, for the attack.
Other types of sexual assault that do not involve penetration,

Other types of sexual assault that do not involve penetration, 
and which represent related behaviours, include toucheurism and frotteurism. These involve, respectively, touching or grabbing strangers, typically females, in a way that provides him with sexual gratiﬁ  cation. The former, in particular, may pass unnoticed by the victim, as attackers will typically touch or grab sexual areas such as 
breasts, buttocks, or crotch, in crowds and similar situations where the incident may be discounted as ‘accidental’ .
Non-contact sexual offences
This group includes ‘peeping T oms’ , ‘ﬂ  ashers’ , and indecent phone 
callers with corresponding psychiatric diagnoses of the paraphilias voyeurism, exhibitionism, and telephone scatalogia, respectively.
Peepers have a penchant to observe an unsuspecting female

Peepers have a penchant to observe an unsuspecting female 
stranger undressing, or couples in the act of copulation. They may masturbate at the scene or later in private while recalling what they saw. Most voyeurs, like most sex offenders who are paraphilic, are aware of their deviant impulses while still adolescent but the behaviour may become chronic.
Exhibitionists derive sexual excitement from exposing their 
genitals to unsuspecting female strangers. The desired reaction is one of ‘shock and awe’ and indifference is a useful response, if the victim has the presence of mind. The perpetrator may masturbate at the time or later in private. Though some cases are particularly intractable, it is unusual to see an exhibitionist still active much past the age of about 40 years old.
The unsuspecting victims of obscene telephone callers are greeted

The unsuspecting victims of obscene telephone callers are greeted 
with a barrage of sexually explicit commentary over the telephone. When this is a habitual practice, accompanied by or followed by masturbation, it is distinguishable from an isolated incident committed as a prank.
In all three of the above non-contact sexual offences, there is 
typically no desire to have further contact with the victim and, indeed, such a prospect often ﬁ  lls the offender with anxiety. However, 
a small minority of these offenders may later commit a more serious sexual offence, even sexually motivated homicide.
(7) Atypical fea-
tures, such as a desire to have personal contact with the victim, or the repeated selection of child victims, may be an early warning sign of such potential and warrants further, expert assessment.
In recent years, paralleling the advance of technology, offenders

In recent years, paralleling the advance of technology, offenders 
have been apprehended for using the Internet as a means of obtain-ing or distributing pornography (especially child pornography) or as a means of contacting children for sexual purposes. Possession of child pornography is an indicator of sexual interest in children and it is associated with self-reported sexual interest in children and with laboratory measurements of changes in penile volume or circumference.
(8)
Assessment of sex offenders
In the context of court remanded cases, the usual pre-trial issues of ﬁ tness (competence) to stand trial and criminal responsibility will 
need to be addressed. Only a small proportion of all sex offenders demonstrate symptoms of psychotic mental disorder, particularly schizophrenia and depressive disorders. However, where those dis-orders are present it is necessary to explore how the symptoms, e.g. delusions or hallucinations, bear speciﬁ  cally on the sexual

offending. It may be found that other psychiatric disorders are of greater importance and that a secondary diagnosis of mental retar-dation or personality disorder, or more particularly, a paraphilia, are more relevant with respect to the offending behaviour. More commonly the court will be interested in sentencing consider-ations, speciﬁ  cally the risk the offender presents to others, and 
whether and what medical treatment and/or other professional 11.8 child molesters and other sex offenders

SECTION 11  forensic psychiatry 1962
interventions might be ordered or recommended by the court in 
order to reduce that risk.
Interview
The interviewer must assume that the subject will be at best guard-ed, or frankly hostile, in their response to the assessment process and it may be difﬁ  cult to achieve the level of afﬁ  nity more com-

monly experienced with non-psychotic general psychiatric patients. A non-judgemental approach is therefore preferable, regardless of the examiner’s personal emotional reaction to the offender’s behav-iour. Few will have presented to the psychiatrist or psychologist voluntarily. Moreover, there is a distinct tendency among sex offenders to prevaricate or frankly lie. It is therefore essential for the examiner to have detailed information about the act or acts that are alleged to have occurred. It has already been noted that denials, rationalizations, distortions, and minimization are the norm with sex offenders. It is not, however, the assessor’s function to judge the issue, in particular when guilt has not been determined by the court.
It is obviously unhelpful, in terms of gaining rapport or obtain-

ing additional information, to accuse the subject of dishonesty. Rather, a sympathetic approach suggesting that sometimes people have difﬁ  culty accepting unpleasant aspects of themselves, may be 
more helpful. Another approach is to invite the subject to explore why the victim made the accusations if they are untrue and whether they can accept, if not the whole, then some part of the allegations against them.
It is also important to remember that, while the individual may 
have been accused of one type of deviant sexual behaviour, other types may have occurred and been undetected. Paraphilic disorders tend not to occur as it were in pure culture but rather in association with other paraphilias, typically at least two or three. Thus, for example, an exhibitionist may have been reported for exposing speciﬁ  cally to children rather than adults and this will suggest an

additional diagnosis of paedophilia. Or, an individual who has been convicted of rubbing himself against women in public places may also have made obscene phone calls and harbour fantasies of rape.
In the case of child molesters it is important to consider how he 
gained access to his victims. Exploration of the methods of ‘groom-ing’ is important in understanding ways to assist the offender to avoid risky situations in the future.
In terms of the overall assessment, identiﬁ  cation of psychopa-
thologies outside the domain of sexual deviation is important. The presence of psychosis will have an implication for the type of treat-ment to be recommended, even if it is not common among sex 
offenders. It seems likely that some such sex offenders’ behaviour is

offenders. It seems likely that some such sex offenders’ behaviour is 
dismissed as a function of the psychosis and underlying paraphilic disorder may easily be discounted or not considered at all. More commonly it will be personality disorders or traits, alcohol or sub-stance abuse, mild-to-moderate depression, and anxiety disorders, rather than major mental illness that will be noted. Attention to these will be an important part of any subsequent treatment or management strategy.
Psychometric testing
Psychometric testing may contribute additional information an overall assessment, in particular where the subject is not forthcom ing 
in a personal interview. There are a number of general personality assessment instruments available. These include the well known 
and widely used Minnessota Multiphasic Personality Inventory
(MMPI ), the Millon Clinical Multiaxial Inventory  (MCMI III ), and 
thePersonality Assessment Inventory  (PAI). All have been exten-

sively used in offender populations including sex offenders, and common proﬁ  les have been identiﬁ  ed. Although none can speciﬁ  -
cally identify a sex offender, information concerning impulsivity, denial, judgement, and general psychopathology may be very useful.
There are also a number of psychological tests that have been 
speciﬁ  cally designed for the assessment of sex offenders. These 
include the Multiphasic Sex Inventory II  (MSI-II ) and the revised 
version of the Clarke Sex History Questionnaire for Males  (SHQ-R ). 
The MSI-II  is designed to measure the sexual characteristics of an

The MSI-II  is designed to measure the sexual characteristics of an 
adult male (though there is a female version too) alleged to have committed a sexual offence or sexual misconduct, including those who deny the allegations. Though standardized in the United States on a large sample of sex offenders it is more widely used. It consists of 560 true/false questions and the completed questionnaire must be sent to the developers for computerized scoring and inter-pretation. The SHQ-R consists of 508 questions and the completed questionnaire may again be sent away for scoring and an inter-pretive report returned.
Laboratory testing

As sex offenders are prone to lie and distort their self-report of deviant interest and behaviours a more objective method of assess-ment has long been pursued. One of the earliest to be developed was the use of the penile plethysmograph (PPG, or phallometry) to measure changes in response to erotic stimulation. This method involves measuring changes in the size of the penis while presenting the subject with carefully selected images, both still and moving, of both sexes and different age groups, and audiotaped descriptions of various sexual activities. There are certainly problems with PPG testing, including the standardization of stimulus materials used, and some offenders are either able to learn to suppress their physi-ological responses or masturbate before the testing in order to render themselves unresponsive.
(8) Nonetheless, the PPG, more

(8) Nonetheless, the PPG, more 
commonly using a circumferential device, or the volumetric method, is extensively used in assessments of sex offenders (for critical review, see Ref.
(10)).
Particularly in the United States, the PPG has come under attack 
as, in addition to standardization and reliability issues, it uses pictures of children whose consent or that of their parents was never obtained. The computer-generated images have been devel-oped to attempt to obviate this concern. More recently the use of virtual reality of computer-generated images has also been used experimentally. Other, less intrusive methods of assessment are also being adopted, including the Abel Screen
(11) which measures time 
spent viewing non-nude images.
Mention must also be made of polygraphy with sex offenders as

Mention must also be made of polygraphy with sex offenders as 
it has been used extensively in many parts of the United States and to some extent in the United Kingdom. The subject is asked ques-tions relating to their sexual interests and activities while their pulse, respiration, and skin conductance are measured. However, research in the area is generally weak and, despite its widespread use and perception of usefulness, particularly for monitoring sex offenders in the community, the method is controversial (for review, see Ref.
(8)).

1963
Assessment of risk in sex offenders
The courts will often wish to have a professional opinion regarding 
the risk an offender presents to re-offend, and it is important to have an understanding of the factors that will contribute to this (see Table 11.8.1).
Risk has been divided into:
1 Static risk, i.e. involving those factors which cannot change, such 
as the offender’s age, sex, or number of previous criminal convic-tions and
2 Dynamic risk, i.e. involving those which potentially could change, 
either as a result of treatment or some other intervention, or sim-ply by the passage of time. This can be further subdivided into relatively stable, though nonetheless potentially changeable, fac-tors such as sexual preferences or negative attitudes, and acute factors, such as access to victims, reversion to substance use, and 
active mental illness.
These are important in estimating an offender’s risk to re-offend.

These are important in estimating an offender’s risk to re-offend. 
Static factors have received the most scientiﬁ  c study and it is chieﬂ  y 
that these have been incorporated  into various act uarial or  statisticalinstruments that have been developed in the past several years, 
based on follow-up studies of samples of sex offenders. Among these instruments the Rapid Risk Assessment of Sex Offender Recidivism (RRASOR), the STATIC-99,
(12) and Sex Offender Risk 
Appraisal Guide (SORAG),(13) are the most widely used. An assessor 
intending to use any of these instruments needs to be thoroughly familiar with the literature on the topic and to have participated in training workshops that are given at conferences from time to time. Useful though these tools can be, too heavy reliance upon them is no substitute for a full understanding of how these were constructed and their limitations.
(14)

(14)
It is rare for paraphilic individuals to present for treatment in order to prevent themselves from becoming a sex offender. Though some paraphilias are not usually associated with criminal charges (e.g. transvestitic fetishism) others, such as paedophilia, are more likely to present through the courts or probation and parole services after
an offence has been committed. It is important to realize that sexu-al preferences are highly resistant if not impossible to change. The most that can be expected with sex offenders who have deviant sexual preferences (paraphilias) is to help them learn to control their behaviour and to recognize that their propensity will always remain in the background, much as alcoholics are advised to con-sider themselves always vulnerable to relapse.

Various psychological therapies have been attempted with sex offenders. Psychodynamically based individual and group treat-ments have been the most commonly used. It has become clearer more recently, however, that cognitive-based therapies (CBT) are the preferable approach to take, although techniques involving classical behaviour therapy, e.g. covert sensitization, are also sometimes used for speciﬁ  c purposes, such as creating aversion to 
deviant arousing images and replacement with non-deviant ones. Cognitive behaviour therapy itself involves helping the subject to develop strategies to alter their thought processes in order to avert their deviant behaviour, to improve their social skills, and to rem-edy their distorted beliefs and attitudes.
There is little or no evidence for the efﬁ  cacy of psychological tr eat-
ments prior to the introduction of CBT. Based on meta-analysis of 
43 published studies, it has been shown that treatment programmes

43 published studies, it has been shown that treatment programmes 
using this approach are associated with a reduction in overall recid-ivism rate from about 17 to 10 per cent.
(15)Nonetheless, there is 
still considerable controversy over the effectiveness of formal sex offender treatment programmes.
(16)
Various medications have been used to treat sex offenders. Based on empirical observations of animals, which become less sexually active following neutering, hormonal treatments that reduce tes-tosterone levels have been extensively employed. All require careful discussion with the potential patient concerning side effects and it is important to obtain written, informed consent.
Oestrogens proved to be problematic because of the serious risk

Oestrogens proved to be problematic because of the serious risk 
of thrombo-embolic complications and a safer alternative was found in Cyproterone acetate (Androcur), an anti-androgen, which is available in Europe, including the UK. Because this drug has not Table 11.8.1  Predictors of sexual offence recidivism
Type of risk factor Predictor
Static Prior sex offence
Prior non-sexual offences
Prior non-contact sex offences
Prior treatment dropoutAny boy victims
Any unrelated victims
Any stranger victimsEarly age of onset
Young age of offender
Minimal cohabitation history
Childhood behaviour problems
Separation from parents as a childAntisocial personality disorder
Prior violation of conditional release
Stable dynamic Sexual preferences, children
Sexual preferences rape/violenceSexually entitled attitudes
Pro-child molester attitudes
Pro-rape attitudes
Lack of adult love partner
Emotional lonelinessLifestyle impulsivity
Ineffective problem-solving skills

Callous and unemotional attitudesAggressive, hostile, and suspicious
Negative social inﬂ  uences
Acute dynamic Access to potential victims
Substance abuseSexual preoccupation
Emotional collapse
Collapse of social support systemRejection of supervision
Acute mental illness
(Reproduced from Webster, C.D. and Huxler, S.J. (2007) Violence risk: assessment and man-
agement. Copyright 2007, John Wiley & Sons, Inc.)11.8 child molesters and other sex offenders

SECTION 11  forensic psychiatry 1964
been made available in North America, Medroxyprogesterone 
acetate (Provera) was introduced. Both however can still be respon-sible for minor side effects such as weight gain, tiredness, and gyn-aecomastia (with Cyperoterone, especially) but also more serious problems including thrombo-embolism and increase in blood sugar. More recently, leuteinizing hormone-releasing hormone (LHRH) agonists such as Leuprolide acetate (Lupron), Goserelin 
(Zoladex), and others, have been found useful as they produce almost total suppression of testosterone production such as would be seen following surgical castration. They tend, however, to be used mainly in very high-risk offenders or those who have failed with other drugs.
(17) All of these hormone-affecting substances, 
though especially the LHRH agonists, have a tendency to leach calcium from the bones
(18) and it is necessary to monitor carefully

(18) and it is necessary to monitor carefully 
for this side effect and to administer antidotes including calcium supplements, vitamin D, and possibly biphosphonates.
The main problem with the hormonal treatments is their lack of 
acceptance by those who might potentially beneﬁ  t. An alternative 
in the form of serotonin-reuptake inhibitors has therefore been better received though double blind trials are still lacking. They depress libido in about 50–60 per cent of cases though higher doses, such as are used with obsessive–compulsive disorder, are often necessary. There appears to be little basis on which to chose one SSRI over another, other than patient tolerance of side effects.
(19)
Ethical problems

(19)
Several ethical issues have been mentioned above in passing. It is, however, worth emphasizing in conclusion that a disinterested professional demeanour is important when assessing sex offenders. No matter what his or her own private views, it is not the place of the clinician to decide on guilt or innocence or in any other way to pass judgement on the offender or alleged offender. Moreover, alienating the offender will present a further impediment to gain-ing information and to providing treatment when indicated and necessary.
It is important, at the assessment stage, to identify for the subject 
the nature of the evaluation, the role of the assessor, and the person or agency for whom they are acting, for example a Child Protection Service, a defence lawyer, or Crown prosecutor. This may deter-mine the degree of cooperation but to not explain this fully and 
simply to present oneself as a ‘doctor’ in a helping role when the

simply to present oneself as a ‘doctor’ in a helping role when the 
intention of the evaluation is solely to provide a risk assessment as opposed to treatment, for example would be unethical.
Certain assessment procedures, such as penile plethysmography 
and polygraphy (when used in a clinical setting) are particularly contentious. Though both may provide useful information, written and fully informed consent should always be obtained beforehand. PPG has been particularly criticized for the use of child images as sexual stimuli when the consent of neither the child nor its parents have been obtained, though the development of computer-generated images may avoid that particular objection.
Finally, when drugs that have been developed and marketed for 
other purposes are used to suppress sexual drive, the patient needs 
to be fully informed of the potential beneﬁ  ts as well as the risks

to be fully informed of the potential beneﬁ  ts as well as the risks 
involved but should not be denied complementary or alternative treatments should they decide not to expose themselves to the potential side effects.Further information
Holmes, R.M. and Holmes, S.T. (2002). Current perspectives on sex crimes .
Sage Publications, London.
Marshall, W.L., Fernandez, Y.M., Marshall, L.E., et al. (2006). Sexual offender 
treatment: controversial issues . John Wiley & Sons, Chichester, 
England.
 1. World Health Organization. (2002). Other risks to health. In The world 
health report 2002: reducing risk, promoting healthy life (Chap. 4) @ 
http://www.who.int/whr/2002/chapter4/en/index9.html
 2. Abel, G., Becker, J., Mittleman, M., et al. (1987). Self-reported sex 
crimes of nonincarcerated paraphiliacs. Journal of Interpersonal 
Violence ,2, 3–25.

2. Abel, G., Becker, J., Mittleman, M., et al. (1987). Self-reported sex 
 3. Spitzberg, B. (1999). An analysis of empirical estimates of sexual 
aggression victimization and perpetration. Violence and Victims ,14,
241–60.
 4. Romans, S., Martin, J., and Mullen, P . (1997). Childhood sexual 
abuse and later psychological problems: neither necessary, sufﬁ  cient 
nor acting alone. Criminal Behaviour and Mental Health ,7,
327–38.
 5. Hislop, J. (2001). Female sex offenders: what therapists, law 
enforcement and child protective services need to know. Issues Press, 
Ravensdale, WA.
 6. Prentky, R. and Burgess, A.W. (2000). Forensic management of sexual 
offenders . Kluwer Academic/Plenum, New Y ork.
 7. Ressler, R.K., Burgess, A.W., and Douglas, J. E. (1988). Sexual homicide: 
Patterns & Motives . D.C. Heath & Co., T oronto.
 8. Seto, M. (2007). Pedophilia and sexual offending against children:

7. Ressler, R.K., Burgess, A.W., and Douglas, J. E. (1988). Sexual homicide: 
 8. Seto, M. (2007). Pedophilia and sexual offending against children: 
theory, assessment, and intervention. American Psychological Association, Washington, DC.
 9. Marshall, W.L. and Fernandez, Y.M. (2003). Phallometric testing with 
sexual offenders . Safer Society Press, Brandon, VT.
10. Laws, R. (2003). Penile plethysmography: will we ever get it right? In 
Sexual deviance: issues and controversies (Chap. 5) (eds. T. Ward, D.R. 
Laws, and S.M. Hudson). Sage Publications, London.
11. Abel, G., Huffman, J., Warberg, B., et al. (1998). Visual reaction 
time and plethysmography as measures of sexual interest in child molesters. Sexual Abuse: A Journal of Research and Treatment ,10,
81–95.
12. Harris, A., Phenix, A., Hanson, K., (2003). STATIC-99 coding 
rules revised—2003 . Solicitor General Canada, Ottawa, Ontario, 
Canada.

81–95.
Canada.
13. Quinsey, V .L., Harris, G.T., Rice, M.E., et al.  (2006). Violent offenders: 
appraising and managing risk . American Psychological Association, 
14. Webster, C.D. and Hucker, S.J. (2007). Violence risk: assessment & 
management . John Wiley & Sons, Chichester.
15. Hanson, K., Gordon, A., Harris, A., et al. (2002). First report of the 
collaborative outcome data project on the effectiveness of psychological treatment for sex offenders. Sexual Abuse: A Journal of Research and 
Treatment ,14, 169–92.
16. Laws, D. R. and O’Donohue, T. (eds.) (2008) Sexual Deviance (2nd ed). 
pp. 7–14. The Guilford Press: New Y ork and London. 
17. Hill, A., Briken, P ., Kraus, C., et al.  (2003). Differential pharmacological 
treatment of paraphilias and sex offenders. International Journal of

treatment of paraphilias and sex offenders. International Journal of 
Offender Therapy and Comparative Criminology ,47, 407–21.
18. Grasswick, L.J. and Bradford, J.M. (2003). Osteoporosis associated with 
the treatment of paraphilias: a clinical review of 7 case reports. Journal 
of Forensic Sciences ,48, 849–55.
19. Greenberg, D. and Bradford, J. (1997). Treatment of paraphilic 
disorders: a review of the role of selective serotonin reuptake inhibitors. Sexual Abuse: A Journal of Research and Treatment ,9, 349–60.

How great a matter a little ﬁ  re kindleth!
New Testament, authorised version (Letter of James, 3:5)
The title of this chapter merits brief comment. Why is arson (ﬁ  re-
raising) a special problem, and why is there a dual title? Arson is a special problem because not only is it regarded as a very serious form of criminal behaviour, but because its detection can be very difﬁ cult. It is an offence that can be committed at ‘one removed’ by 
an offender, and it may sometimes involve unintended victims. Forensic psychiatrists will meet a number of arsonists in the course of their work but, increasingly, general psychiatrists are likely to come across them from time to time, for two reasons. First , the 
High Court in England and Wales has suggested that psychiatric reports are advisable in all cases where the motivation for the offence is unclear. Second , as will become clear from the writer’s

High Court in England and Wales has suggested that psychiatric reports are advisable in all cases where the motivation for the offence is unclear. Second , as will become clear from the writer’s 
later comments, there has been a worrying increase in arson com-mitted by young adults and children. Thus it is probable that child and adolescent psychiatrists are likely to come across cases more frequently. However, Soothill indicates a word of caution. He sug-gests that over-reliance upon psychiatric involvement may tend to ‘medicalize’ socially problematic behaviour.
(1) The dual title that 
heads this chapter indicates the legal term used in the United 
Kingdom to describe acts of unlawful ﬁ  re-raising. However, the 
term is not in universal use; readers will ﬁ  nd that in other jurisdic-
tions (notably in the North Americas) the terms are ﬁ  re-raising, 
ﬁ re-setting, incendiarism, and in certain speciﬁ  c instances, pyro-

mania and pathological ﬁ  re-raising.(2) The term ﬁ  re-raising is used 
in this chapter since the alternative terminologies can be subsumed under it.
(3,4)
Brief historical context
The phenomenon of ﬁ  re, its uses and misuses, has ﬁ  gured exten-
sively in myth, legend, and literature. For example, Prometheus is 
said to have stolen ﬁ  re from the Gods and the myth became the 
mainspring for much psychoanalytic theorizing about ﬁ  re-raising 
behaviour.(3) There are numerous early historical references to 
incendiary mixtures and devices, including sketches for mortars by 
Leonardo da Vinci.(5) In the mid-nineteenth century, the medical 
profession became interested in the explanation of ﬁ  re-raising

profession became interested in the explanation of ﬁ  re-raising 
behaviours; and subsequently, adherents of psychoanalysis pro-posed various complex and somewhat doubtful explanations for such conduct. In particular, they linked ﬁ  re-raising behaviour to 
sexual disturbance of one kind or another. Although sexual prob-lems do appear in the backgrounds of some  recidivist ﬁ  re-raisers, 
the importance of the links has, in the present writer’s view, been somewhat overstated.
(6) Having said this, it should perhaps be 
noted that the phenomenon of ﬁ  re is not infrequently linked lin-
guistically to aggression and sexuality. For example, we speak or write of ‘white hot rage’ , ‘heated arguments’ , ‘inﬂ  amed passions’ ,

guistically to aggression and sexuality. For example, we speak or write of ‘white hot rage’ , ‘heated arguments’ , ‘inﬂ  amed passions’ , 
to have the ‘hots’ for a sexual partner. Language is the conveyor of cultural values and attitudes and can be a powerful force in inﬂ  uencing our modes of thinking and expression about the 
phenomenon of ﬁ  re in its many manifestations.
The size of the problem
During the past two decades concern about the increase in ﬁ  re-
raising has been expressed worldwide. Table 11.9.1 gives the num-ber of offenders convicted of arson in England and Wales  for the 
years 1999–2003.
These ﬁ  gures only provide a partial picture, since it is often very 
difﬁ cult to establish whether a ﬁ  re has been started deliberately 
(ﬁ res of doubtful origin or, if strongly suspected, malicious ignition).

(ﬁ res of doubtful origin or, if strongly suspected, malicious ignition). 
Happily, recent advances in forensic science have brought about improvements in the detection rate. A more reliable picture of the real size of the problem can be obtained from the United Kingdom Fire Statistics . The latest ﬁ  gures indicate a continuing worrying 
number of deliberate ﬁ  res—some 91 200 in 2004 and, in particular, 
the number of attacks on vehicles and schools. ‘Arson in vehicles . . . accounts for 60% of all deliberately set ﬁ  res at 55,000 per year’ . In 
2004, in the United Kingdom, there were 840 school ﬁ  res, slightly 
down on 896 in the previous year. Fatalities dropped from 117 in 
2003 to 88 in 2004. Overall, the number of deliberate ﬁ  res decreased 
by 21 per cent in 2004,
(8) an encouraging trend. The cost of ﬁ  res in Arson (ﬁ  re-raising)
Herschel Prins11.9

Table 11.9.1  Arson, number of offenders found guilty of arson in 
England and Wales for the period 1999–2003
1999 2000 2001 2002 2003
2475 2470 2644 2427 2501
(Extracted from Home Ofﬁ  ce, (2004). Criminal statistics, England and Wales, 2003, Cm 
6361. TSO © Crown Copyright(7).)

SECTION 11  forensic psychiatry 1966
purely monetary terms is considerable; for example, ﬁ  gures from 
the Association of British Insurers (ABI) indicate ‘that the cost of commercial fire claims in 2005 was 791 million pounds’—a record.
(9)
Legal aspects
Legal deﬁ  nitions of arson vary from country to country. In England 
and Wales, prior to 1971, arson was an offence at common law. Currently, it is dealt with under the Criminal Damage Act, 1971. Similar provisions apply in Northern Ireland. In Scotland, it is dealt with under various common law offences. Section 1 of the 1971 Act states:
1 A person who without lawful excuse destroys or damages any 
property belonging to another intending to destroy or damage such property or being reckless as to whether any such property would be destroyed or damaged shall be guilty of an offence.
2 A person who without lawful excuse destroys or damages any 
property, whether belonging to himself or another:

(a) inte nding to destroy or damage any property or being 
reckless as to whether any such property would be destroyed or damaged; and
(b) inte nding by the destruction or damage to endanger the 
life of another or being reckless as to whether the life of another would be thereby endangered; shall be guilty of an offence.
3 An offence committed under this section by destroying or 
damaging property by ﬁ  re shall be charged as arson  (emphasis 
added).
NOTE:  Recklessness has recently been clariﬁ  ed by the High Court 
as follows: ‘A person also acts recklessly within the meaning of Section 1 of the 1971 Act with respect to (i) a circumstance where he is aware of a risk that exists or will exist; (ii) a result when he is aware of a risk that will occur; and, it is in the circumstances known to him, unreasonable to take the risk’ .
(10)

(10)
The seriousness with which arson and endangering life is recorded 
is reﬂ  ected in Section 4 of the Act where both are punishable by 
maximum penalties of life imprisonment.
Classiﬁ  cation, motivation, and management
An early, large-scale attempt to classify ﬁ  re-raisers was undertaken 
by Lewis and Y arnell.(11) For an account of this and other earlier 
studies see Prins.(12) Faulk proposed two useful broad groupings. 
Group I  consisted of those cases in which the ﬁ  re served as a means 
to an end (for example, revenge, fraud, or a plea for help); Group II
consisted of those cases where the ﬁ  re itself was the phenomenon 
of interest.(13) Some years ago the present author, together with 
two psychiatrist colleagues, examined the ﬁ  les of a group of 113 
imprisoned arsonists being considered for parole.(14) From this 
small (and admittedly highly selective) sample a rudimentary classiﬁ  cation was devised. (See Table 11.9.2). This has been used by

small (and admittedly highly selective) sample a rudimentary classiﬁ  cation was devised. (See Table 11.9.2). This has been used by 
others as starting points for their own and perhaps more sophisticated classiﬁ  cations. The present writer has more recently 
modiﬁ  ed slightly this earlier classiﬁ  cation.
(3) Despite modiﬁ  cation 
it can be seen to still have certain weaknesses since it collates the behavioural characteristics of ﬁ  re-raisers, various types of ﬁ  re-
setters and their motivations.(15)
Rix broadened our original classiﬁ  cation to include attempts to 
gain rehousing, carelessness, ‘anti-depressant’ (to relieve depressed feelings), and ‘proxy’ (in which the offender had acted on behalf of another who had borne a grudge).
(16) Barker, an experienced 
forensic psychiatrist, in a wide-ranging and meticulous study of the psychiatric aspects of ﬁ  re-raising, suggested that future classiﬁ  ca-

tions need to be more sharply focussed, emphasizing that arson should be seen ‘merely as a symptom’ to be viewed in the context of the whole person, not only to delineate different ‘syndromes’ of arsonists but also to identify individual points of therapeutic intervention and future dangerousness.
(15)
Recent work by Canter and Fritzon has carried this focus for-
ward. They suggest four themes to arson. Two related to expressive
acts; (a) those that are realized within the arsonist’s own feelings, being analogous to suicide, and (b) those that are acted on objects, like the burning of symbolic buildings. The two others relate to instrumental  acts; (c) those that are for personal indulgence, 
similar to personal revenge; and (d) those that have an object focus such as hiding evidence from a crime (emphasis added).

(17) More 
recently Canter and Fritzon’s work has been replicated successfully by Almond et al.
(18) and Hakkanen et al.(19)
(a) Some general characteristics of ﬁ  re-raisers
It is a reasonable generalization to state that ﬁ  re-raisers appear 
to be mostly young adult males who have exhibited behavioural difﬁ culties from an early age (see Kennedy et al.
20 for a systematic 
review of the literature on this aspect and Repo and Virkkunen(21)). 
A significant proportion of these youthful fire-raisers have problems of alcohol abuse and intelligence levels lower than average.
(21,22)  Females who commit repeated acts of ﬁ  re-raising 
and show some degree of mental disorder and self-mutilating behaviours are more likely to be awarded a mental health disposal by the courts than their male counterparts (see Coid et al.
(23)and

(23)and
Noblett and Nelson(24)).Table 11.9.2  Suggested classiﬁ  cation of the motives of arsonists 
(ﬁ  re-raisers)
(a) Arson committed for ﬁ  nancial reward (insurance fraud, etc)
(b)  Arson committed to conceal another crime (for example, burglary or 
homicide)
(c) Arson committed for political purposes (terrorist and associated activities)(d)  Self-immolation as a political gesture. (Not arson as such, but included 
here for completeness, see Prins
(12))
(e)  Arson committed for mixed motives (for example, during the phase of 
minor depression, as a cry for help, or as a result of abuse of alcohol or 
other drugs)
(f)  Arson due to the presence of formal mental disorder (for example, severe

(f)  Arson due to the presence of formal mental disorder (for example, severe 
affective disorder, schizophrenic illnesses, organic mental disorder, mental impairment (learning disability))
(g)  Arson due to motives of revenge—ag ainst (i) an individual or individuals; 
(ii) against society or others more generally
(h)  Arson committed as an attention-seeking act (but excluding motives set 
out under (e) above) and arson committed as a means of deriving sexual satisfaction and/or excitement (for example, some forms of pyromania)
 (i) Vandalistic arson (by young adults and children)

1967
Motivation
T o conform to the requested word limit for this chapter, categories 
(a), (b), (c), and (d) in Table 11.9.2 are not considered here. Detailed discussion of these and illustrative case vignettes may be found in Prins.
(12)
(a) Fire-raising committed for mixed and unclear reasons
These are cases in which it is difﬁ  cult to ascribe a single speciﬁ  c 
motive and which cause signiﬁ  cant problems in assessment. They are 
likely to include the presence of a degree of mild (reactive) depres-sion which may lead the ﬁ  re-raiser to direct anger at a spouse or 
partner; thus revenge may also play a part (see discussion below). This group may also include cases in which the ﬁ  re-raising may be a 
disguised plea for help, or a reaction to sudden separation or bereave-ment; in a proportion of these cases alcohol appears to play a part.
(b) Fire-raising due to serious mental disorder

Functional psychoses, notably the schizophrenias, may play a part in some acts of ﬁ  re-raising. Such offenders will most likely be 
detained in secure hospitals or units. Manic depressive psychosis features occasionally, a classic case being that of Jonathan Martin, the nineteenth century arsonist who set ﬁ  re to Y ork Minster.
(12)
(c) Fire-raising associated with ‘organic’ disorders
Occasionally, brain tumours, injury, epilepsy, dementia or metabolic 
disturbance may play a part. For example, although the epilepsies are not commonly associated with ﬁ  re-raising (or other serious

disturbance may play a part. For example, although the epilepsies are not commonly associated with ﬁ  re-raising (or other serious 
crimes for that matter) one should always be on the lookout for the case in which the crime has been committed when the person appeared not to be in a state of clear consciousness or when onlookers were present. Examples of organic states and their rela-tionship to ﬁ  re-raising are provided elsewhere.
(3,25–27) The relation-
ship between learning disabilities and ﬁ  re-raising is discussed by 
Prins(12) and Clare et al.(28)
(d) Fire-raising motivated by revenge
Those incidents motivated by revenge are potentially the most 
dangerous. Such offenders are like the monster in Mary Shelley’s Frankenstein  who said ‘I am malicious because I am miserable’ . 
These are the ﬁ  re-raisers who have serious problems with their

These are the ﬁ  re-raisers who have serious problems with their 
feelings of anger and frustration caused by real or imagined wrongs. In considering the links between motives of revenge, it is important to stress the hazards of trying to place motivations for ﬁ  re-raising 
in discrete categories; the vengeful ﬁ  re-raiser may show clear signs 
of identiﬁ  able mental illness (for example, delusional jealousy), 
may be learning disabled and/or physically impaired, or may not be diagnosable as ‘ill’ in any formal psychiatric sense.
(e) Pyromania
The diagnostic criteria for pyromania are set out in DSM-V(Rev) TSM (1994) on page 615.
(29) The condition and its diagnosis may

(29) The condition and its diagnosis may 
be said to be one of exclusion. It is dealt with in detail by McElroy in Chapter (4.13.1) of this volume. Perhaps its manifestation of excitement for those who show the disorder is best exempliﬁ  ed by 
the poet Walt Whitman in his Poems of Joy  (1860).
I hear the alarm at dead of night,
I hear the bells—shouts!
I pass the crowd—I run!
The sight of ﬂ  ames maddens me with pleasure.(f) Sexually motivated ﬁ  re-raising
The possible connection between ﬁ  re-raising and sexuality has

The possible connection between ﬁ  re-raising and sexuality has 
already been referred to. The lack of frequent association should not blind clinicians and others to its possible existence in certain cases, or its similarity to sex offending. Fras puts it well—as follows: ‘In its comparative, stereotyped sequence of mounting pressure . . . it resembles the sexual perversions, as it may parallel them in its imperviousness to treatment’ .
(30) It is not without signiﬁ  cance that 
imprisoned ﬁ  re-raisers appear to have more than their fair share of 
psychosexual difﬁ  culties and partnership problems. In Hurly and 
Monahan’s Grendon Prison study, a large proportion of their sam-ple reported difﬁ  culties in social relationships with women.
(31)
Suggestions for management
The word ‘Suggestions’ is used to indicate that what follows is not

(31)
The word ‘Suggestions’ is used to indicate that what follows is not 
intended to be prescriptive; it must be emphasized that no single form of management is likely to be effective. At the assessment stage it is vital to treat every case as singular. Any attempt at assess-ing the future risk of ﬁ  re-setting must view the behaviour on the 
basis of all the facts (for example, full details of the index offence and antecedent history). One can then begin to take the rounded and long view as advocated by Scott in his seminal paper on dangerousness. Assessors of whatever discipline will gain much 
from absorbing Scott’s balanced and insightful views.
(32) Pointers 
to successful assessment and management may be summarized as 
follows:
◆ Distinguish the fraudulent ﬁ  re-raiser. But note that the ﬁ  re-

follows:
setter who appears to be engaged upon a fraudulent insurance claim to ‘rescue’ a failing business may be suffering from an underlying depressive illness. The history-taking in such cases needs to be painstaking and searching. Do not ‘run’ with what appears to be the obvious explanation.
◆ Distinguish the politically motivated. But, note that some politi-cally motivated ﬁ  re-raisers may also have serious mental health 
problems. In an age when fear of terrorist attacks abounds and the remedies appear to be of the ‘knee-jerk’ variety, a cool head in the assessment process is essential.
◆ Distinguish the vandalistic and the differences between young people who set ﬁ  res out of boredom or for ‘kicks’ from child ﬁ  re-
setters who are more likely to have seriously dysfunctional social backgrounds.
(33, 34)

(33, 34)
◆ Distinguish those who are driven to set ﬁ  res by clear evidence of 
mental disorder, notably functional psychosis, severe anti-social personality disorder (psychopathy), organic disorder, and learn-
ing disability.
◆ Distinguish those who appear to exhibit pyromania as deﬁ  ned in 
DSM-IV TSM(Rev).
◆ Distinguish those rarer cases in which sexual disorder (and in 
particular sexual dysfunction) may have played a signiﬁ  cant 
role.
◆ Distinguish the vengeful. It is important to remember that feel-ings of vengefulness may persist over long periods of time and such ﬁ  re-raisers may be adept at concealing their vengeful feel-
ings. These ﬁ  re-raisers have some features in common with the 
delusionally jealous (Othello-type syndrome).11.9 arson (fire-raising)

SECTION 11  forensic psychiatry 1968
Successful assessment and management (which ideally should be 
a ‘seamless’ process) needs to rest upon a multi-faceted and multi-team approach. An excellent example of such a multi-disciplinary approach may be found in Clare et al .
(28) They describe their 
management of a case that necessitated an understanding of both physical and learning disability combined with a capacity to work intensively using eclectic behavioural techniques over a prolonged period of time. Despite minor setbacks, the offender-patient, who had been subject at one time to containment in a high security hospital, remained free of his long-standing ﬁ  re-raising behaviour 
at 4-year follow-up. It would also be unwise to believe that psycho-analytically based psychotherapy had no place in the management of psychotic and seriously personality disordered ﬁ  re-raisers. Cox 
described some very productive work with such patients in Broadmoor.

(35) Social skills training of one kind or another has a 
very important part to play. Many ﬁ  re-raisers (particularly the 
vengeful and those with a pyromania diagnosis) are socially inept and believe themselves to be misunderstood by society. T echniques aimed at improving their self-regard, self-image, and social compe-tence can help to minimize recidivism.
Not only is arson (ﬁ  re-raising) a very worrying offence for the 
reasons given, but it has shown an increase in recent years. Moreover, the ‘proﬁ  le’ of those convicted of arson has shifted over 
the years with an increased proportion of female offenders. And, in a very important recent study, Soothill et al. showed at 20 year

the years with an increased proportion of female offenders. And, in a very important recent study, Soothill et al. showed at 20 year 
follow-up that the proportion of those reconvicted for arson had more than doubled. The authors conclude with the sobering obser-vation that ‘the situation in relation to arson has deteriorated signiﬁ  cantly over the past 40 years’ .
(36) The causes of ﬁ  re-raising 
are complex and attempts at classiﬁ  cation have not been entirely 
successful. Viewing ﬁ  re-raising as a ‘symptom’ appears to offer 
the best hope for more successful diagnosis and management. The brief survey in this chapter has merely touched upon the topic. The suggestions for further reading and the references should assist those who wish to pursue the topic in further depth.
My thanks to Mrs Janet Kirkwood for so ably preparing the ﬁ  nal 
version of the manuscript.
Arson Prevention Bureau. The Bureau publishes the Arson Intelligence

Arson Prevention Bureau. The Bureau publishes the Arson Intelligence 
Newsletter  at regular intervals. Available from Arson Prevention 
Bureau, 51 Gresham Street, London, EC2V 7HQ.
Enayati, J., Grann, M., Lubbe, S., et al.  (2008). Psychiatric 
Morbidity in Arsonists referred for Forensic Psychiatric Assessment in Sweden. The Journal of Forensic Psychiatry and 
Psychology, 19, 139–147.
Ofﬁ ce of the Deputy Prime Minister (ODPM) (2006) Fire Statistics  (UK)
2004 and Fire Statistics Monitor  Issue 1/06. 28.2 ODPM. 
(These publications provide extensive statistical and 
descriptive data).
Repo, E. and Virkkunen, M. (1997). Outcomes in a sample of Finnish 
ﬁ re-setters. Journal of Forensic Psychiatry ,8, 127–37.
Swinton, M. and Ahmed, A. (2001). Arsonists in maximum security. 
Medicine, Science, and the Law ,41, 51–7.References

 1. Soothill, K. (1991). Arson. In Principles and practice of forensic 
psychiatry  (eds. R. Bluglass and P . Bowden), pp. 779–86. Churchill 
 2. Barnett, W. and Spitzer, M. (1994). Pathological ﬁ  re-setting: 
1851–1991: a review. Medicine, Science, and the Law ,34, 4–20.
 3. Prins, H. (1994). Fire-raising: its motivation and management .
 4. Prins, H. (2005). Offenders, deviants or patients ? (3rd edn) (Chapter 7). 
 5. MacDonald, J.M. (1977). Bombers and ﬁ  re-setters . Thomas, 
 6. Prins, H. (2001). Arson and sexuality. In The encyclopaedia of 
criminology and deviant behaviour , Vol. 3 (eds. C.D. Bryant, N. Davis, 
and G. Geis), pp. 11–5. Brunner-Routledge, New Y ork.

6. Prins, H. (2001). Arson and sexuality. In The encyclopaedia of 
 7. Home Ofﬁ  ce. (2004). Criminal statistics, England and Wales, 2003 .
Cm6361. TSO.
 8. Arson Prevention Bureau. (2006). Arson intelligence newsletter .(87).
 9. Arson Prevention Bureau. (2006). Arson intelligence newsletter . (87), 
and Fire Statistics, UK, 2004 .ODPM (2006), London.
10. R v. G., and another. (2003). UK HL50. Reported in The Independent 
Law Report . 22.10.03.
11. Lewis, N.D.C. and Y arnell, H. (1951). Pathological ﬁ  re-setting 
(Pyromania). Nervous and mental disease monograph 82 . Coolidge 
Foundation, New Y ork.
12. Prins (3). Notably pp. 98–103.
13. Faulk, M. (1988). Basic forensic psychiatry . Blackwell Science, Oxford.
14. Prins, H., T ennent, G., and Trick, K. (1985). Motives for arson 
(ﬁ re-setting). Medicine, Science, and the Law ,25, 275–8.

15. Barker, F. (1994). Arson: a review of the psychiatric literature . Oxford 
16. Rix, K.J.B. (1994). A psychiatric study of adult arsonists. Medicine, 
Science, and the Law ,34, 21–34.
17. Canter, D. and Fritzon, K. (1998). Differentiating arsonists: a model 
of ﬁ re-setting actions and characteristics. Legal and Criminological 
Psychology ,3, 73–96.
18. Almond, L., Duggan, L., Shine, J., et al. (2005). T est of the arson system 
model on an incarcerated population. Psychology, Crime and Law ,11,
1–15.
19. Hakkanen, H., Puolakka, P ., and Santilla, P . (2004). Crime scene 
actions and offender characteristics in arsons. Legal and Criminological 
Psychology ,2, 197–214.
20. Kennedy, P .J., Vale, L.E., Khan, S.J., et al. (2006). Factors predicting 
recidivism in child and adolescent ﬁ  re-setters. Journal of Forensic

recidivism in child and adolescent ﬁ  re-setters. Journal of Forensic 
Psychiatry and Psychology ,17, 151–64.
21. Repo, E. and Virkkunen, M. (1997). Y oung arsonists: history of conduct 
disorder, psychiatric diagnoses and criminal recidivism. Journal of 
22. Taylor, J.L., Thorne, I., Robertson, A., et al. (2002). Evaluating a 
group intervention for convicted arsonists with mild and borderline intellectual disabilities. Criminal Behaviour and Mental Health ,
12, 282–93.
23. Coid, J., Wilkins, J., and Coid, B. (1999). Fire-setting, pyromania and 
self-mutilation in female remanded prisoners. Journal of Forensic 
Psychiatry ,10, 119–30.
24. Noblett, S. and Nelson, B. (2001). A psycho-social approach to 
arson—a case-controlled study of female offenders. Medicine, Science, 
and the Law ,41, 325–30.

25. Carpenter, P .K. and King, A.L. (1989). Epilepsy and arson. The British 
Journal of Psychiatry ,154, 554–6.
26. Byrne, A. and Walsh, J.B. (1989). The epileptic arsonist. The British 
Journal of Psychiatry ,155, 268.
27. Hurly, W. and Monahan, T.M. (1969). Arson: the criminal and the 
crime. British Journal of Criminology ,9, 4–21.

1969
28. Clare, I.C.H., Murphy, D., Cox, D., et al. (1992). Assessment and 
treatment of ﬁ  re-setting: a single case investigation using a cognitive 
behavioural model. Criminal Behaviour and Mental Health ,2, 253–68.
29. American Psychiatric Association. (1994). Diagnostic and statistical 
manual of mental disorders  (DSM-IV-4th edn). American Psychiatric 
30. Fras, I. (1983). Fire-setting and its relationship to sexuality. In Sexual
dynamics of anti-social behaviour  (eds. L.D. Schlesinger and E. Revitch), 
pp. 192–203. Thomas, Springﬁ  eld, IL.
31. Hurly and Monahan (27).
32. Scott, P .D. (1977). Assessing dangerousness in criminals. The British 
Journal of Psychiatry ,131, 127–42.33. Santilla, P ., Hakkanen, H., Alison, L., et al. (2003). Juvenile ﬁ  re-
setters: crime scene actions and offender characteristics. Legal and 
Criminological Psychology ,8, 1–20.
34. Perrin-Wallqvist, R. and Nerlander, T. (2003). Fire-setting and playing

34. Perrin-Wallqvist, R. and Nerlander, T. (2003). Fire-setting and playing 
with ﬁ  re during childhood and adolescence: interview studies of 18 
year-old male draftees and 18-19 year-old female pupils. Legal and 
Criminological Psychology ,8, 151–8.
35. Cox, M. (1979). Dynamic psychotherapy with sex offenders. In Sexual
deviation  (2nd ed) (ed. I. Rosen), pp. 306–50. Oxford University Press, 
Oxford.
36. Soothill, K., Ackerley, E., and Francis, B. (2004). The criminal careers 
of arsonists. Medicine, Science, and the Law ,44, 27–40.11.9 arson (fire-raising)

Stalking
Paul E. Mullen11.10
What is stalking?
Stalking is now used to describe a problem behaviour characterized 
by repeatedly inﬂ  icting unwanted intrusions and/or communica-
tions on another in a manner which creates fear and/or signiﬁ  cant 
distress.(1) The intrusions can involve, following, loitering nearby, 
maintaining surveillance, and making approaches. The communi-cation can be via telephone (including SMS), letter, electronic mail, grafﬁ  ti and notes attached, for example, to the victims’ car. 
Stalking can be associated with a range of harassments which though not part of the core behaviours are all too frequent. These include, ordering goods and services on the victim’s behalf (late night pizza’s being a favourite) damaging property, spreading malicious rumours, vexatious complaints, threats, ‘cyber terrorism’ , and assault.
There are two basic patterns to stalking.
(2) The first involves

(2) The first involves 
repeated incursions predominantly in the form of approaches and following perpetrated most often by a stranger and lasting only a day or so. The second is characterized by a range of both communications and intrusions, is usually perpetrated by an ex-intimate or acquain-tance, and lasts for weeks, months, or even years. The ﬁ  rst type can 
be intense and distressing at the time but uncommonly culminates in a physical attack and though upsetting, rarely inﬂ  icts long-term 
psychological or social damage. The second type is associated not infrequently with psychological and social damage to the victim and will involve physical assaults in up to a third of victims.
The epidemiology of stalking
Estimates of the prevalence of stalking, as with any other phenomenon, will vary according to deﬁ  nition, sampling, method 
of enquiry, and the willingness of subjects to respond and respond frankly.

(2–7) Reported lifetime rates of victimization for women are 
between 8 per cent and 22 per cent and for men between 2 per cent and 8 per cent. Most victims are female (70–80 per cent), most stalkers are male (80–85 per cent), with 20–25 per cent involving same gender stalking, typically male on male.
Cyberstalking
Cyberstalking has attracted considerable interest but few systematic studies. Even the deﬁ  nitions employed of cyberstalking 
vary widely.
(8–10) As beﬁ  ts an online phenomenon much of the information about it is to be found on the Internet rather than in 
the more traditional sources of academic knowledge.
Sheridan and colleagues(11) in an important study concluded 
that cyberstalking was usually one more invasive technique for pursuing stalking rather than a distinct type of activity.
Cyberstalking can include the use of the Internet and SMS 
facilities to:
1Send repeated unwanted messages .

2Order goods and services on the victim’s behalf .
3Publicizing private information of a potentially damaging or 
embarrassing nature . Including circulating e-mails, placing infor-
mation on the web containing personal details, and occasionally explicit sexual images.
4Spreading false information . A wide range of misinformation can 
be spread via the Internet with the authors of these calumnies able, should they wish and have the necessary skills, to hide their identity.
5Information gathering online about a victim  can cover a wide 
range of material from addresses, employment histories, to ﬁ nancial details. There are even services for tracing people 
available online which can be utilized by stalkers whose victim has eluded them.
6Identity theft  goes beyond simply pretending to be the victim for

6Identity theft  goes beyond simply pretending to be the victim for 
the purposes of ordering goods or initiating contacts to an attempt to assume not just the name but the actual property and attributes of the victim.
7Encouraging others to harass the victim . This can cover activities 
such as placing communication purporting to be from the victim on web likely to attract unwanted communications or attentions. The most egregious example involved a rejected stalk-er who posted personal advertisements in his ex-partner’s name and giving her address which suggested she enjoyed being raped and solicited such attentions. Apparently six men actually came to her house in response to these provocations.
(12)
Impact on victims

(12)
Stalking is both an act of violence in itself which causes psycho-logical distress and social disruption, and is a harbinger of assault. Being stalked can produce a corrosive state of fear, arousal, and

1971
helplessness. As with domestic violence for most victims it is not 
the blows which are the most destructive but living in a chronic state of intimidation and the expectation of imminent intrusion. In the study of Pathé and Mullen
(13) the majority reported disrup-
tive levels of anxiety with intrusive recollections of the stalking, 
sleep disturbance, lowered mood, with 25 per cent admitting con-sidering suicide to escape the situation. A community study found increased rates of psychiatric morbidity and post-traumatic symp-tomatology amongst those stalked for more than 2 weeks but not amongst those who had experienced the briefer periods of harassment.
(14) Dressing and colleagues(7,15) also document signif-
icant psychological and social disruption in response to being stalked with 56 per cent reporting agitation, 44 per cent increased anxiety, 41 per cent sleep problems, and 28 per cent increased depression.
Stalkers: classiﬁ  cations and typologies

Stalking, like most forms of complex human behaviour, can be the 
outcome of a wide range of psychological, social, and cultural inﬂ uences. Some stalk in hope, some in anger, some in lust, some in 
ignorance, and many in mixtures of the above. In an attempt to advance the understanding of stalkers a range of typologies and classiﬁ  cations have been advanced.
(16)
Classifying stalkers by the nature of their prior relationship with 
the victim has the advantages of simplicity and utility. The classiﬁ  -
cation advanced by Mohandie and colleagues(17) represent the best

cation advanced by Mohandie and colleagues(17) represent the best 
supported by empirical evidence of such approaches to date. They divide stalkers into those with and without a prior relationship. Those with a prior relationship are subdivided into ex-intimates (ex-partners both long term and more casual) and acquaintances (including friends, colleagues, and professional contacts). Those without a prior relationship are subdivided into ﬁ  rstly ‘public 
strangers’ who were encountered through the media or in their public roles, and secondly into ‘private strangers’ encountered by chance in the interactions of everyday life. This classiﬁ  cation’s

strangers’ who were encountered through the media or in their public roles, and secondly into ‘private strangers’ encountered by chance in the interactions of everyday life. This classiﬁ  cation’s 
greatest utility is in predicting the risks of assault, with those with a prior intimate relationship constituting the highest risk group and those targeting public strangers the lowest. In their view the pursu-ers of public strangers are the most likely to be psychotic with those pursuing ex-intimates being relatively impervious to therapy but 
responsive to criminal sanctions.
The typology ﬁ  rst developed by Mullen and colleagues
(1,18)
depends primarily of the context in which the stalking emerges and 
the motivations which initiated and sustained the behaviour. Its appeal has been primarily to clinicians managing stalkers and their victims.
(19) There are ﬁ  ve main types:
1The rejected  whose stalking begins in the context of the break-

down of a close relationship. The stalking is initially motivated either by the desire for reconciliation or to express the rage at rejection, with a mixture of both being quite common. The stalk-ing is often sustained by the pursuit of the ex-partner becoming a substitute for the lost relationship with the satisfactions from intrusion and control replacing those of intimacy.
2The intimacy-seeker  who is pursuing love. The stalking begins 
in the context of a life bereft of intimacy and is motivated by the hope, or ﬁ  rm expectation, of obtaining a loving relationship 
with a stranger or casual acquaintance on whom they have ﬁ  xed 
their amorous attentions. The pursuit is sustained in the face of indifference or outright rejection because better a love based on 
fantasy or delusion than no love at all.
3The incompetent suitor  who is pursuing a sexual encounter or

3The incompetent suitor  who is pursuing a sexual encounter or 
friendship. This usually begins in the context of loneliness and is motivated by a desire to start some form of relationship with someone who has attracted their interest. This group often pursues intensely with multiple intrusions but rarely persists for more than a day or so, presumably because multiple rebuffs bring few rewards.
4The resentful , whose stalking starts in the context of a grievance 
at being unjustly treated or humiliated. The initial motivation is revenge but this gives way to the satisfactions obtained from the sense of power over someone who has previously been experi-enced as an oppressor, or the representative of oppressors.
5The predatory , which begins in the context of the desire to act out

5The predatory , which begins in the context of the desire to act out 
violent or sexual fantasies often of a sadistic or paedophilic nature. The initial motivation is to gain information about the movements of a potential victim (usually a stranger but occasionally an acquaintance). The stalking continues because of the satisfactions accruing not just from voyeurism but from the excitement and sense of power which comes from rehearsing the planned attack in fantasy whilst watching the future victim.
Each of the stalker types, hopefully with the exception of the 
predatory, has correlates in normal behaviour. When relationships break down one partner is often confused or distressed by the separation and seeks to understand, to reconcile, or to express anger. The incompetent suitor is kin to the awkward adolescent male and the socially inept adult who fails to traverse effectively the social mineﬁ  elds of courting or simply making acquaintance. The

intimacy seeker is the adolescent crush and the enthusiastic fan writ large. Even the resentful is not far removed from some seekers after justice and those asserting their rights. In theory the bound-ary between persistent approaches as part of socially acceptable behaviour and the crime of stalking are difﬁ  cult to pin down. 
In practice the distinction is rarely a problem. Stalkers are those 
who repeatedly force themselves on another person in a manner which creates obvious distress. It is the total disregard, or blindness to, the disturbance and often fear that their behaviour creates which distinguishes the stalker from their more normal counterparts. Sometimes the stalkers are so caught up in their own world they are oblivious to their effect on others. Sometimes they are blinded by delusion. Sometimes self-righteousness makes them indifferent. But sometimes they delight in the effect they produce in their victim.
Psychopathology of stalkers

Stalkers are rarely, if ever, drawn from the psychologically adequate or socially able of the world. The estimates of the proportion of stalkers whose behaviour is directly related to mental disorders varies according to where the researchers derived their sample. For example, Zona and his group
(20) whose sample contained many 
who pursued Hollywood celebrities had a signiﬁ  cant number with 
erotomanias and morbid infatuations.
In broad terms psychotic disorders are relatively frequent in the 
intimacy seeking group. In the resentful type it is the paranoid 
disorders which unsurprisingly predominate, though most are not 11.10  stalking

SECTION 11  forensic psychiatry 1972
associated with frank delusion. The rejected often have problems 
around dependency, rigidity, control, and self-esteem with sub-stance abuse and depressive states on occasion complicating the picture, but psychotic states are uncommon. The incompetent suit-ors are socially disabled sometimes by shyness, sometimes by narcissism, sometimes by intellectual limitations, sometimes by culture, sometimes by disorders such as Asperger’s syndrome, rare-ly by psychosis, but always by interpersonal insensitivity or indif-ference. The predatory are sexually perverse and not infrequently have marked psychopathic traits, but again are rarely psychotic.
Attempts have been made to conceptualize stalking as a manifes-
tation of obsessive–compulsive disorder. Stalkers are certainly often obsessive in the everyday sense of that word in their pursuit of the victim. They rarely however regard their behaviour as unjustiﬁ  ed

let alone irrational, and few see their persistence as senseless. They may resist the urges to stalk on occasion but for the most part devote themselves wholeheartedly to the pursuit. Anxiety is more likely to be generated by the fear of failure, or of consequences, than by not acting on their impulses to stalk. They may well spend many hours thinking about the object of their unwanted atten-tions, and in the resentful reliving the experiences of actual or supposed injustice, so in that sense they are ruminators. Personality traits of rigidity, rumination, and the overvaluing of order are not infrequently so marked in rejected and resentful stalkers as to justify a label of an obsessional personality. In short, the behaviour often has an obsessive quality but the state of mind rarely conforms to that found in obsessive–compulsive disorders.
Attachment theory has unsurprisingly been evoked to explain

Attachment theory has unsurprisingly been evoked to explain 
stalking. That stalkers as a group don’t do interpersonal relation-ships very well is obvious. Evidence exists that insecure attachment styles predominate amongst rejected stalkers, the intimacy seekers may have the type of secure attachment style only sustainable by delusion, and the incompetent and resentful favour the dismissive style. This is useful in assessment and management but what connection it may have with any theory of early development is speculative and here as elsewhere more likely to be productive of mythologizing than good clinical practice.
The stalking of health professionals
Health care professionals have a heightened vulnerability to being stalked by their patients and clients.
(21–24)  The risk stems largely

(21–24)  The risk stems largely 
from resentful and disappointed patients but in part from lonely and disordered people who misconstrue sympathy and attention for romantic interest. While some stalking behaviours constitute little more than minor irritations, they may also ruin a clinician’s career.
Sandberg et al.
(25) studied an inpatient psychiatric service report-
ing 53 per cent of clinical staff had been stalked by patients. Galeazzi and colleagues
(26) found 11 per cent of the mental health profes-
sionals in an Italian service had been stalked for lengthy periods by patients. Purcell and colleagues
(14) surveyed a randomly selected

(14) surveyed a randomly selected 
sample of 1750 psychologists (73 per cent female). The lifetime prevalence of stalking by clients was 19.5 per cent with 8 per cent being stalked in the preceding 12 months. Most victims were working in direct client care (95 per cent) and experienced rather than new entrants to the profession. Stalkers fell predominantly into either the intimacy seeking (19 per cent) or resentful (42 per cent) types. Over 30 per cent of psychologists in this study were subjected to vexatious complaints by their stalker. The impact of 
complaints to professional boards, health ombudsmen, and other agencies of accountability can be devastating.
T oo often in the past therapists who fell victim to stalking by

T oo often in the past therapists who fell victim to stalking by 
patients had to bear the additional burden of implied or overt crit-icism from colleagues to the effect that, had they more adroitly managed the therapeutic encounter and the resultant transference, they would not now ﬁ  nd themselves in this predicament. There 
should be no sympathy with blaming the victim, even if it comes in the guise of technical advice or supervision. Being stalked is a risk inherent in the therapeutic process. Our colleagues should be accorded support and help, if for no other reason than we do not know when it may be our turn to face the pursuit of the vengeful or lustful patient.
Risk assessment and risk management

Stalking came to prominence because it was regarded as a risk factor for violence. Subsequently it became clear that the damage inﬂ icted on those who are stalked could also encompass signiﬁ  cant 
social and psychological damage.
(23)
Assessing and managing the stalker requires a primary focus 
on the risks they present to the victim. Nevertheless the risk that stalkers incur from their own behaviour also needs to be considered (Table 11.10.1). The conﬂ  ict between the stalker’s desires and the

victim’s interests are obvious, but they are at one in being at risk of damage from the stalking situation. There can be a tragic symme-try between the victim forced to live an increasingly restricted life in a state of constant fear, and the stalkers devoting all their time and resources to a damaging and ultimately self-defeating pursuit. The victim’s and the perpetrator’s lives can be laid waste. This is not to argue for equivalence between victim and perpetrator but merely to note they share the chance of disaster. A perspective which encompasses the risks to stalkers and victims has the advan-tage for health professionals of reducing the ethical dilemma when 
treating stalkers around whose interests one is serving, the patient’s 
or their victim’s. We help both to the extent that we contribute to stopping the stalking, or reducing its damaging consequences.
The empirical basis for evaluating risk in the 
stalking situation

Risk assessment in stalking situations is currently hampered by a 
paucity of either retrospective or prospective studies of representa-
tive samples. Clinicians do not, however, have the luxury of deferring action until such evidence emerges. They must, for the present, depend on integrating knowledge from stalking research, borrowing from the systematic studies of risk in other areas, and drawing on clinical experience.
(27)
The risk of continued or recurrent stalking
The duration of stalking is longest for rejected stalkers pursuing ex-intimates and intimacy seekers, with the incompetents usually pursuing only brieﬂ  y. Women, here as elsewhere, are more persis-
tent than men.
(6,13)  Once stalking has continued for more than 
2 weeks the chances are high that it will continue for months.

The risks of psychological and/or social damage
Female victims of stalking report a greater psychological impact than male victims.
(5,13) Clinically, the distress and disruption to

1973
victims is usually most obvious in ex-intimates pursued by their 
rejected partners, perhaps because of the higher levels of violence and intimidation combined with the complexity, as well as the intensity, of feelings stirred up in this situation.
(13) Psychological 
distress was higher amongst victims who were subjected to pro-longed and repeated following and the experience of property theft or destruction.
(2,13,28,29)  The relationship between psychological 
impact and the experience of physical violence is less clear, despite its intuitive appeal.
(29,30)
The risks of violence
(a) Prior relationship
Victims who have shared a prior intimate relationship with their stalker are at a high risk of physical violence.
(1,4,13,20,31–35)  Purcell 
and colleagues(6) for example reported in a random community

and colleagues(6) for example reported in a random community 
sample that ex-intimates were the most likely to be attacked (56 per cent), followed by estranged relatives or previous friends (36 per cent), then casual acquaintances (16 per cent), work-related contacts (9 per cent), and ﬁ  nally strangers (8 per cent). Such ﬁ  nd-
ings should not be interpreted, however, as suggesting that victims of stalkers who are not ex-intimates are in little danger of physical violence. A chance of between 8 per cent and 36 per cent of being assaulted is no small risk.(b) Threats
Between 30 per cent and 60 per cent of stalking victims are threat-ened.
(1,20,31) In a community-based study 44 per cent of those 
threatened were subsequently assaulted and 73 per cent of victims assaulted by their stalker had previously been explicitly threatened.
(6)
In short threats predict violence and should be taken seriously.
(c) Mental disorder

(6)
Research has generally concluded that psychotic stalkers are less likely to be physically violent than their non-psychotic counter-parts but the relationship to personality disorder remains unclear.
(1,34,36,37)
(d) Substance abuse
Substance abuse is associated with violence in the stalking situation.
(1,38–40)
(e) Prior offending and antisocial behaviour
The empirical data on the association between past criminal or violent behaviour and stalking violence is inconsistent, however the balance of the evidence favours such a relationship.
(1,34,39,41)
(f) Demographic variables
The gender of stalkers has repeatedly been shown to have no impact on the prevalence of either threats or assault.
(4–6,13,42)Table 11.10.1  The stalker’s clinical risk factors and future hazards speciﬁ  c to stalking situation
Risk factor Management possibilities include
Clinical

Clinical
1.  Mental state e.g. depression, delusional preoccupations Active treatment usually involving pharmacotherapy2.  Substance abuse Referral to a specialist substance abuse service where possible or to self-help groups like AA3.  Anger Anger management remains a problematic area. Ideally those with anger control problems should 
be receiving special help independently of the broader management of their stalking
4.  Attitudes towards, and beliefs about, the victim which 
sustain stalkingAppropriate legal interventions; CBT and focussed psychotherapies aimed at such areas as; 
abandoning love, accepting loss, confronting misperceptions
5.  The conviction that they are right to engage in stalking Enhancing victim empathy. Confronting false attributions using CBT6.  The refusal to engage in any therapy, or conform to legally

5.  The conviction that they are right to engage in stalking Enhancing victim empathy. Confronting false attributions using CBT6.  The refusal to engage in any therapy, or conform to legally 
imposed restrictions on access to the victimUltimately confronting the stalker with consequences (e.g. through breaching parole, referring 
back to court, etc.); employing motivational interviewing strategies to assist the stalker to appreciate the need for intervention
7.  Social incompetence Social skills training, therapies aimed at enhancing self-efﬁ  cacy8.  Paraphilia Sex offender program incorporating CBT +/− pharmacotherapy as indicated
Future hazards
1.  Likely future contact with the victim Every effort should be made to enforce a total ban on direct contact or direct communi cations
2.  Lack of a feasible set of plans for avoiding a recrudescence 
of stalkingEnsure structured plan around avoiding provocations and using protections re: stalking; CBT to

of stalkingEnsure structured plan around avoiding provocations and using protections re: stalking; CBT to 
assist the stalker to overcome the compulsion to stalk
3.  That the underlying precipitants remain unresolved Focussed psychotherapy aimed at the areas identiﬁ  ed in the formulation; social skills training for 
the inept; assistance abandoning the relationship; the treatment of paraphilias using CBT +/− 
pharmacotherapy as indicated
4.  Continuing instability of residence and/or employment Assistance obtaining housing; career counselling; and active employmen t rehabilitation as 
indicated and appropriate
5.  Continuing social isolation Use of clubs, day centres, recreational counselling, domestic pets6.  Likely low level of compliance with legal restraints on 
contact with victimEnsure knowledge of consequences of breaches and never collude—implicitly or explicitly—with 
avoiding those consequences

7.  Likely low level of cooperation with any treatment 
programmeUse of compulsory community treatment orders either imposed by court or as part of mental 
health legislation11.10  stalking

SECTION 11  forensic psychiatry 1974
(g) The nature of the stalking
Violence is predicted by escalating intrusiveness and intensity of 
the stalking behaviour. The strongest association is to physical intrusions into the victims house or place of work.
(36)
The assessment process
Initial assessments of stalkers often occur in the context of pre-sentence or parole board evaluations. Victims may be encountered in a wider range of contexts, many seeking help from general rather than forensic mental health professionals. Stalkers usually lack insight into their behaviour and tend to deny, minimize, and rationalize their actions. Victims often minimize the experience of stalking and over-emphasize their own responsibility for the harassment, which should be of no surprise to anybody experi-enced in working with victims in other contexts. Conversely, the problem of false claims of stalking victimization cannot be entirely ignored.

(43) This makes it essential to assess collateral information 
from such sources as witness statements, victim impact reports, judges’ sentencing remarks, and professional to professional con-tacts, conﬁ  dentiality allowing. Attempts to contact the victim when 
assessing the stalker, or the stalker when assessing the victim are, in our opinion, best avoided. However skilfully managed, such contacts tend to be experienced by the victim as the professional acting as an agent of the stalker, and by the stalker as support for their beliefs that this is a misunderstanding within a mutual relationship rather than a unilateral imposition of unwanted attentions.
(27)

(27)
The management of stalkers remains very much the province of forensic mental health professionals and even amongst them it is a specialist area. Basic approaches to identifying potentially remedi-able risks and their management however is presented in. Victims of stalking are however likely to be seen by a wide range of mental health professionals.
Reducing the impact on victims
Stalking victims will often present with signiﬁ  cant problems with 
anxiety symptoms and depressed mood. The symptom complex of PTSD will be present to a greater or lesser extent in most victims of prolonged and intense stalking. Like many victim groups there may be a reluctance to disclose the details or even the existence of the traumatic experiences. As noted earlier self-blame is not infrequently part of the picture.
Given the high proﬁ  le of stalking there are a number of disturbed

Given the high proﬁ  le of stalking there are a number of disturbed 
people who claim they are being stalked as a way to express their distress, claim attention, or give form to their persecutory delusions.
(24,43)  This group, particularly if delusional, are often 
obvious given the ﬂ  amboyant, implausible, and exuberant accounts 
of victimization. Care should be taken in dismissing claims of being stalked, however, as there are some very unpleasant stalkers out there some of whom stalk leaving few, if any, objective signs. False victims require help and treatment not rejection, but they require quite different treatment from actual victims.
Stalking victims need ﬁ  rst and foremost good psychiatric care. 
Manage the stress symptoms, treat the depression, ameliorate the distress, and provide adequate support. Individual treatment is best initially but the use of groups for long-term support and treatment is worth considering.
(44) What follows is a brief account of stalking

(44) What follows is a brief account of stalking 
speciﬁ  c interventions.
1 Informing others. When you are stalked it is essential to inform 
those you live with, work with, and are friends with. This per-forms three functions:
(a) It allows you a ‘reality check’ on your fears that stalking is 
(b) It enables others to support you and equally important avoid 
inadvertently assisting the stalker.
(c) It prevents those around you being put at risk by ignorance 
provoking the stalker thereby also falling victim.
3 Avoid contact and/or confrontation. All contacts or direct 
communications with a stalker risks reinforcing their behaviour. Confrontation and worse still violence, legitimizes, and encour-ages their violence. Once stalking is established it is usually too late to simply sort things out by having a meeting.
4 Documentation. The best protection for stalking victims lies

4 Documentation. The best protection for stalking victims lies 
in the criminal law. The police are more likely to respond appropriately if you can demonstrate that the behaviour is occur-ring and make it relatively easy for them to pursue the allega-tions. Keep the letters (dated), record the phone calls and retain the tapes, keep a diary noting approaches and where possible witnesses to those events, record verbatim any threats and obtain witnesses or photographs of any property damage. Not only will this be invaluable for a later prosecution it is part of the victim taking control back over their lives.
5 Restraining, non-molestation, apprehended violence and other

5 Restraining, non-molestation, apprehended violence and other 
such orders. Sometimes these civil orders do provide an effective means of reducing or stopping stalking. Police often advise their use, hopefully not just to avoid work. Some jurisdictions insist on obtaining such orders prior to considering criminal prosecu-tion. Reservations have to be expressed, however, not only about their effectiveness (totally ineffective for intimacy seekers, rela-tively ineffective for the rejected and intermittently effectively for the resentful) but also about the level of insecurity and distress consequent on their breach and facing the frequent indifference 
of the police to such breaches.
6 Increased security. Simple cheap security measures such as 
good locks, movement triggered lighting outside the house, and securing the mail box may provide a degree of reassurance and a modicum of security.
Not a few psychiatrists, at least of my generation, have difﬁ  culties

Not a few psychiatrists, at least of my generation, have difﬁ  culties 
with the notion of problem behaviour like stalking being a proper subject for mental health concern. Psychiatry has traditionally been wary of concerning itself directly with criminal and antisocial behaviours.
(45,46)  The approach taken in this chapter was, in con-
trast, to deﬁ  ne a pattern of behaviour destructive to the interests 
of perpetrator and victim and then to examine its origins, effects, and potential therapeutic management. That this is an enterprise with risks for the ethical integrity of psychiatry is undoubted. But recognizing that psychiatry can have a role in assessing and manag-ing problem behaviours, without ﬁ  rst performing obfuscating 
transformations into supposed mental disorders such as paraphilias

1975
and impulse control disorders, allows a more clear sighted and 
effective approach to areas of human activity where our interven-tion can beneﬁ  t both the actor and the wider community.
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Querulantenwahn (Ger.) A form of so called paranoia in which there 
exists in a patient an insuppressible and fanatic craving for going to law in order to get redress for some wrong which he believes done to him. Individuals who fall victim to this disorder are always strongly predisposed . . .. extremely egotistical . . . know everything better . . . differs from other forms of paranoia in so far as the wrong may not be quite imaginary . . . the more he fails the more he becomes convinced that enormous wrong is being done to him . . . neglects his family and his business . . . going down the road to ruin.
(1)
The above quote neatly summarizes classical psychiatry’s view of querulous, or litigious, insanity as a form of paranoia. A problem-atic form, however, in that the querulousness was usually based on a genuine grievance and was often regarded as developing on the basis of predispositions rooted in the sufferer’s personality.
(2–4)

(2–4)
As to treatment Krafft Ebing(3) notes the ‘necessary and beneﬁ  cent 
(effects of the) appointment of a guardian and commitment to an asylum’ but regretted that this ‘takes place unfortunately only after they have used up their property, insulted the courts, and disturbed public order’ (p. 395).
Psychiatries interest in the querulous (from the Latin to mutter 
and to mumble) waned rapidly in the latter half of the twentieth century. The diagnosis was appealed to less and less and the litera-ture largely fell silent.
(5) In part the disappearance of querulous-
ness, and even the querulous patient, from the realms of psychiatry paralleled the decline of paranoia as a diagnostic entity. In part it reﬂ ected psychiatries increasing reluctance to play the role of social

regulator. Probably most importantly the emerging culture of individual rights made pathologizing complainants potentially disastrous as it could deprive them of access to the major social mechanisms for obtaining justice.
(6) Psychiatry lost interest in the 
querulant, however, at the very time that the ‘culture of complaint’ drew more and more vulnerable people into the systems of com-plaint management. Agencies of accountability, which range from Ombudsmen’s offices, via registration boards, to complaints departments, are now almost all faced with the problems created by a small group of people pursuing grievances with a persistence and insistence out of all proportion to the substantive nature of their

claim. It is estimated that 20–30 per cent of the resources of these agencies are being consumed by less than 1 per cent of unusually persistent complainants. In the civil and family courts the number of interminable cases being pursued, often by unrepresented liti-gants, escalates year by year. Last, but not the least, querulants pur-suing what they regard as their rights through repeated petitions and intrusive approaches to politicians and heads of state distract protection services from more substantial threats.
(7–9)
The querulant pursue their vision of justice through litigation in the court, through petitions to the powerful, and ﬁ  nally through 
the various agencies of accountability. In practice all three avenues are often explored. In the nineteenth and early twentieth century it was the civil courts in which these dramas were usually played out. T oday the main burden falls on the complaints organizations.

It is not easy to distinguish the querulant from the difﬁ  cult 
complainant or even from social reformers and victims of gross injustice. A simple typology may assist:
1Normal complainants  are aggrieved seeking compensation, 
reparation, or just an apology. They will accept conciliation and reasonable solutions, though they may become persistent and insistent if provoked by inefﬁ  ciency or injustice.
2Difﬁ  cult complainants  also seek compensation and reparation 
but often want in addition retribution. They tend from the outset to anger, to seeing themselves as the victim of others intentional malevolence, and to resist all solutions but their own. Eventually, however, they will settle for the best deal they can obtain.
3Altruistic reformers  who pursue goals of social progress via the 
courts, petitions, and complaints. They sacriﬁ  ce their personal

courts, petitions, and complaints. They sacriﬁ  ce their personal 
interests in pursuit of better outcomes for others. Though they may have a political agenda which is sectarian (e.g. antigenetically Querulous behaviour: 
vexatious litigation, abnormally persistent complaining and petitioning
Paul E. Mullen11.11

SECTION 11  forensic psychiatry 1978
modiﬁ  ed foods, fathers rights) they do not have idiosyncratic 
and personalized objectives.
4Fraudsters  who knowingly pursue false or grossly exaggerated 
claims.
5The mentally ill  whose claims are driven by delusional preoccu-
pations frequently bizarre in nature which reﬂ  ect underlying dis-
orders often of a schizophrenic type.
6The querulous  who seek personal vindication in addition to com-
pensation, reparation, and retribution. They are on a quest for justice which becomes totally preoccupying. Unlike reformers, and most of the difﬁ  cult, there is an obvious discrepancy between 
the provoking event and the importance attached to it by the querulous. They appear to seek not resolution but continuation of the conﬂ  ict. They lay waste to their social and 
economic functioning.
The querulous are usually males who ﬁ  rst become embroiled

The querulous are usually males who ﬁ  rst become embroiled 
in complaining and claiming in their fourth or fifth decade. Premorbidly they were often able to function reasonably well. They rarely have criminal records or prior psychiatric contact, and sub-stance abuse is not prominent. Many had relationships but by the time they reach psychiatrists they have usually alienated their fam-
ily and friends. Querulants are often disappointed people who feel 
their qualities have been ignored and left unrewarded. Their pur-suit of justice offers an opportunity to vindicate their lives and obtain the public recognition so long denied. Their personalities tend to have the traits of self-absorption, suspiciousness, and obses-sionality combined with an enviable capacity for persistence.
Clinically they typically present as energized, garrulous indivi-

duals eager to convince you of the merits of their case. There is an enthusiasm which can seem almost manic but unlike the manic they are totally focussed and almost impossible to distract from their narrative of injustice. They may come with bags overﬂ  owing 
with documents testifying to their misplaced scholarship. If chal-lenged they usually become patronizing as they pedantically refute all objections, to their complete satisfaction. Alternatively they may become menacing and overtly threatening.
Communications from querulants were noted by Lester and 
colleagues
(10) to be often characterized by:
◆ Multiple methods of emphasis including, underlining, high-lighting (often in multiple colours), and capitalization
◆ The generous use of inverted comas, exclamation marks, and question marks
◆ Numerous foot and marginal notes

◆ The use of attachments, often extensively annotated, some poten-tially pertinent (e.g. letters received, copies of legislation), others of less obvious relevance (e.g. Magna Carta, UN Declaration of Human Rights)
◆ And many many pages.
The content of communications may also be unusual sometimes 
containing:
◆ Legal, medical, and other terms used frequently but often incorrectly
◆ Repeated rhetorical questions
◆ A curious combination of rambling repetitiveness with pedantry (more difﬁ  cult to describe than recognize)◆ Veiled threats to harm themselves or others if their wishes are 
not granted or
◆ Exaggerated politeness and attempts to ingratiate.

The querulous can only be adequately assessed by considering the development over time of their behaviour as well as their state of mind. In an interview they may present as merely overenthusiastic and over hopeful pursuing their legitimate rights with at worst a degree of fanaticism. It is the unfolding of their story which reveals the damage they are suffering, and they have inﬂ  icted on those 
around them.
Case history (representing an anonamized conﬂ  ation 
of several cases )
A man in his late forties made a complaint to the local bank

A man in his late forties made a complaint to the local bank 
manager over the manner in which mortgage documents had been prepared. There were grounds for legitimate concern as irregulari-ties had occurred, though of a minor nature and of a kind which might have been expected to be to his advantage. His initial com-plaint to the bank was rejected. He appealed unsuccessfully to the banking ombudsman. He stopped paying the mortgage and initi-ated civil action. Over the next 5 years he pursued his complaints with the human rights commissioner, the securities exchange com-missioner, consumer rights organizations, via further civil litiga-tion, and petitions to Parliament and the Queen. The foreclosure on the mortgage intensiﬁ  ed the complaints and litigation. Finally 
he made a series of bomb threats leading to his prosecution and

he made a series of bomb threats leading to his prosecution and 
referral. When assessed he was righteously indignant, believing he had been right to take extreme action to bring attention to an injus-
tice which had destroyed him and his family and threatened the very economic fabric of the nation. He ﬁ  rmly believed he was owed 
millions in punitive damages, and that when he inevitably prevailed this would bring down the transnational banking corporation which owned his particular branch ofﬁ  ce. He regarded himself as a 
whistle blower who would be publicly recognized as one of the major social reformers of his generation. The changes over time in the grievance, the agents, his state of mind, social situation, beliefs, and aims are presented schematically in Table 11.11.1
Traditionally psychiatry has attempted to distinguish between

Traditionally psychiatry has attempted to distinguish between 
deluded querulants, who are in the business of mental health services, and the non-deluded, who are not. Unfortunately for this approach the querulous present a formidable phenomenological challenge. They advance their ideas plausibly making apparently rational connections between the underlying grievance, which is almost always based on some actual injustice, and their current claims and complaints. Unlike many deluded patients, their beliefs do not usually seem to arise either on the basis of some difﬁ  cult to

understand interpretation of an event, or from an idiosyncratic insight into reality. The querulous offer a detailed and apparently logical account of the emergence of their grievances and the progress of their quest for justice. Reasonable that is if taken in cross section but not when considered over time when there emerge gross discrepancies between the supposed initiating cause and subsequent behaviour. The persuasive presentation can obscure the essential absurdity of the quest and distract attention from the chaos they have created for themselves and those around them. The temptation is to normalize the clinical presentation but this is

1979
to ignore both the peculiarity of their behaviour and beliefs, as well 
as the devastation they have wrought on their own lives. Sometimes the querulous are obviously deluded, sometimes they appear to inhibit that borderline which is captured in such terms as overvalued ideas and delusion like ideas. Debates over the phenomenological niceties should not, however, distract from recognizing the patho-logical nature of such querulousness.
The querulous are sometimes regarded as obsessional. The level 
of preoccupation, the ruminative quality of their thinking, and the pedantic attention to the minutiae of their case, all suggest obsession. Certainly most, if not all, querulants have obsessional personality traits. But the querulant does not regard their core beliefs and the behaviour as absurd or absurdly insistent. Quite the reverse they know they are right and are totally identiﬁ  ed with their 
ideas. The querulous therefore may be regarded as obsessive or

ideas. The querulous therefore may be regarded as obsessive or 
ﬁ xated but not as having an obsessional disorder.
(6)
Our courts and agencies of accountability are designed to deliver 
conciliation, arbitration, reparation, and compensation, but rarely retribution, except in the exceptional case of punitive damages, and never personal vindication. The querulous seek above all personal vindication and retribution so from the outset are doomed to fail.
One view is that it is the failures of the courts and complaints 
organization that drive claimants to become querulous. Charles Dickens articulates this in his great novel Bleak House arguing the courts ‘give to monied might the means abundantly of wearying 
out the right. . . (which) so overthrows the brain and breaks the heart to leave its worn out lunatics in every madhouse’ . Lester and colleagues
(10) in their study of unusually persistent complainants 
failed to document any signiﬁ  cant differences between the manner

failed to document any signiﬁ  cant differences between the manner 
in which the complaints had been dealt with in those whom became querulous and those who did not. This suggests a role in the patho-genesis for vulnerability not just reacting to provocations.
The impact of querulousness can be reduced by improved 
recognition and improved management practices in courts and agencies of accountability.
(6) Psychiatrists currently only tend to be 
involved after the situation has reached the stage of the querulant either becoming seriously depressed or being charged with threats, violence, or contempt.
The literature on the therapeutic management of the querulous 
is both small and predominantly discouraging.
(11) Ungvari,(12)

however, reported successful treatment using pimozide. Our own experience is that relatively low doses of atypical antipsychotics are helpful though the response is slow in coming often taking months before there is obvious improvement. The ﬁ  rst problem is attaining 
some semblance of a therapeutic alliance with the patient. This requires avoiding being caught up in discussions of the rights and wrongs of their quest. The focus should be on the price they and their family are paying for the pursuit.
(6) Interestingly some of 
those who come on orders from the court which mandate treatment will accept medication and other therapeutic interventions as they wish to make clear they abide by the law. Paradoxically they can Table 11.11.1  A case of querulous behaviour: the changes over a 5-year period in the various domains illustrating the descent from the

reasonable if over hopeful and oversensitive to the unrealistic and unrealizable
Grievance Agents
Errors in mortgage documents Bank’s accountantPotential ﬁ  nancial loss Plus managerActual ﬁ  nancial loss Plus senior management
Victim of major fraud and theft Plus banking ombudsmanSystem wide corruption Plus lawyers and judges
A campaign of ﬁ  nancial corruption threatening the nations economic stability Plus wife
Plus various public agenciesPlus policePlus prime ministerPlus secret services
State of mind Social situation
Rigid discontented man obsessional traits but articulate and ambitious Moderately successful small businessman, married, two chi ldren, but 
experiencing ﬁ  nancial pressures and marital problems
Increasingly ﬁ  xated on grievance Business begins to fail as all his attention moves to grievancePursuit of justice subordinates all other concerns Marriage breaks downIncreasingly convinced he is being persecuted and spied upon Alienates few friends he had

He is a man of destiny ﬁ  ghting forces of national and international corruption Bankruptcy
Living aloneDestitute
Beliefs Aims
That order and due process are the bedrock of civilization Compensation for malfeasance (the sum rapidly escalating over the yea rs)
Bad things happen not by chance but because of carelessness or malevolence Reparation—a return of his house mortgage freeThat he had never received the recognition and rewards he deserved Retribution—punitive damages, sackings, and criminal prosecut ions
He was destined for greatness Vindication by public recognition as a whistle blower who had reformed the 
banking system
(Reproduced from P . E. Mullen and G. Lester, Vexatious litigants and unusually persistent complainants and petitioners: from qu erulous paranoia to querulous 
behaviour, Behavioural Sciences and the Law ,24, 333–49, copyright 2006, John Wiley & Sons, Inc.)11.11  querulous behaviour: vexatious litigation, abnormally persistent complaining and petitioning

SECTION 11  forensic psychiatry 1980
be ultra compliant patients. A number have continued voluntarily 
in treatment after the end of the order though they never acknowl-edge either that they were in error or in need of treatment because of their querulousness. What changes is the involvement in the querulous ideas, the degree of preoccupations, and the behaviour, but the core belief that they were right never wavers. Querulous behaviour appears to be sustained by a range of cognitive distor-tions including:
◆ Those who do not fully support their cause are enemies.
◆ Any lack of progress is the product of malevolent interference from someone.
◆ Any compromise is humiliating defeat.
◆ The grievance is the deﬁ  ning moment of their lives.
◆ That because they are in the right the outcomes they seek must 
be not only possible but necessary.
These distortions are open to challenge and amelioration if

These distortions are open to challenge and amelioration if 
not completely overcoming. In theory the cognitive therapy approaches advocated for the delusions should also be of value.
(13,14)
The problem with the therapeutic management of querulous behaviour is that we have no trial of treatment or even much beyond case reports. This reﬂ  ects widespread prejudice that the 
querulous are not the business of mental health and even if they are they are untreatable. Hopefully if this neglect is overcome and querulous behaviour is once more recognized as a legitimate concern for mental health professionals then systematic studies of therapy will follow. For the present the querulous destroy the fabric of their lives as well as creating distress and occasionally damage to those around them.
Charles Dickens. Bleak House —Multiple Editions.

Mullen, P .E. and Lester, G. (2006). Vexatious litigants and unusually 
persistent complainants and petitioners: from querulous paranoia to querulous behaviour. Behavioural Sciences and the Law ,24, 333–49.Douglas, M. (1992). Risk and blame, essays in cultural theory . Routledge, 
London.
 1. Hack Tuke, D. (1892). A dictionary of psychological medicine ,
pp. 1060–1. Churchill, London.
 2. Jaspers, K. (1923). General psychopathology  (trans. J. Hoenig and 
M.W. Hamilton 1963). Manchester University Press, Manchester.
 3. Krafft Ebing, R. (1905). Textbook of insanity  (trans. C.G. Chaddock), 
pp. 397–9. Davies Company, Philadelphia.
 4. Kraepelin, E. (1904). Lectures in clinical psychiatry  (trans. and 
ed. T. Johnstone). Bailliere, Tindall and Cox, London.
 5. Caduff, F. (1995). Querulanz-ein verschwindendes psychopatholgisches 
Verhaltensmuster? Fortschritte der Neurologie-Psychiatrie ,63,
504–10.

504–10.
 6. Mullen, P .E. and Lester, G. (2006). Vexatious litigants and unusually 
persistent complainants and petitioners: from querulous paranoia to 
querulous behaviour. Behavioural Sciences and the Law ,24,
333–49.
 7. James, D.V ., Mullen, P .E., Meloy, J.R., et al. (2007). The role of 
mental disorder in attacks on European politicians 1990–2004. Acta 
Psychiatrica Scandinavica ,116(5), 334–44.
 8. Mullen, P .E., James, D.V ., Meloy, J.R., et al. (in press). The ﬁ  xated 
and the pursuit of public ﬁ  gures. Journal of Forensic Psychiatry and 
Psychology .
 9. Poole, S. (2000). The politics of regicide in England, 1760–1850: 
troublesome subjects . Manchester University Press, Manchester & 
New Y ork.
10. Lester, G., Wilson, B., Grifﬁ  n, L., et al.  (2004). Unusually persistent

New Y ork.
10. Lester, G., Wilson, B., Grifﬁ  n, L., et al.  (2004). Unusually persistent 
complainants. The British Journal of Psychiatry , 184,  352–6.
11. Dietrich von, H. (1968). Der Querulant Munchener Medizinische 
Wochenschrift ; 14, June 110 Jahrgang, pp. 1445–50.
12. Ungvari, G.S. (1993). Successful treatment of litigious paranoia with 
pimozide. Canadian Journal of Psychiatry ,38, 4–8.
13. Chadwick, P ., Birchwood, M., and Trower, P . (1996). Cognitive therapy 
for delusions, voices and paranoia . John Wiley and Sons, Chichester.
14. Bentall, R. and Kinderman, P . (1994). Cognitive processes and 
delusional beliefs: attributions and the self behaviour. Research and 
Therapy ,32, 331–41.

Over the last decade, the issue of domestic violence has been trans-
formed from a position of ‘selective inattention’ to becoming a high-priority social and public health issue.
(1) Although it is now 
recognized that experiences of domestic violence are associated with adverse mental as well as physical health outcomes for the victim, this has not always been the case. Early psychiatric writings tended to attribute responsibility for violent relationships, to the masochistic traits of women who are drawn to and then fail to separate, from abusive and violent partners. During the 1980s and 1990s, however, the perception of victims of domestic violence, or ‘battered women’ began to change, towards an understanding that the responsibility for domestic abuse lies with the wife beater, rather than the wife beater’s wife.
This change came about as a result of several factors; ﬁ  rst,

This change came about as a result of several factors; ﬁ  rst, 
effective lobbying by the feminist movement which put the issue of domestic violence ﬁ  rmly on the political agenda; second, the 
inﬂ uence of a number of researchers who began to conceptualize 
the psychological and behavioural problems seen in victims as the consequence, rather than the cause of, domestic violence, for example through the identiﬁ  cation of a speciﬁ  c ‘Battered Woman 
Syndrome’ ,
(2) and ﬁ  nally the introduction of Posttraumatic Stress 
Disorder as a distinct psychiatric diagnosis in 1980 (APA, 1980).
Deﬁ nition
Domestic violence is currently deﬁ  ned in the United Kingdom 
as ‘Any incident of threatening behaviour, violence or abuse 
(psychological, physical, sexual, ﬁ  nancial or emotional) between 
adults who are, or have been in an intimate relationship’ .(3) Most

adults who are, or have been in an intimate relationship’ .(3) Most 
cases of domestic violence involve the abuse of a woman by her male partner, however, domestic violence may also involve other family members, same sex partners, and the abuse of men by women partners.
The estimated prevalence of domestic violence varies, according to the deﬁ  nition being used and the population surveyed. Based on an 
analysis of 48 population-based studies from around the world, the prevalence of domestic violence is between 10 and 69 per cent over a lifetime and between 3 and 52 per cent in the past year.
(4) In the

(4) In the 
United Kingdom, around 16 million incidents of domestic violence are recorded annually, with a lifetime prevalence of 21 per cent lifetime and 4 per cent in the past year for women and 10 per cent lifetime and 2 per cent in the past year, for men.
(5) Women who 
report domestic abuse consistently report experiencing more incidents and more injuries and being more fearful of their partner, than male victims.
(5)
Aetiological factors
Domestic violence arises out of a complex interplay of personal, situational, and socio-cultural factors. Poverty, alcohol use, low academic achievement, being single, separated or divorced, and witnessing or experiencing violence as a child are the most impor-tant individual risk factors for domestic violence.
(4) Poverty

(4) Poverty 
operates at an individual and societal level, in that it places increased stress on the individual and the family system and also acts as a marker for a number of other social conditions (e.g. low education, overcrowding) that combine to increase the risk of domestic violence. Alcohol use by the perpetrator also signiﬁ  cantly increases 
the risk of domestic violence.
(4,5) Women appear to be at particu-
larly high risk of domestic violence during pregnancy and the immediate post-partum period.
(6) Experiences of domestic abuse 
in childhood and adolescence are associated with an increased risk of perpetration, for men
(4) and re-victimization, for women(7) in 
adult relationships. Inequality and a power imbalance within the relationship
(8) and in the wider society,(9) also increases the risk of

(8) and in the wider society,(9) also increases the risk of 
domestic violence. Higher rates are found in societies where men have economic and decision-making power in the household, where women do not have easy access to divorce, and where there is a high level of public acceptance of men’s right to discipline their wives.
(4,9)
Mental health effects of domestic violence
Domestic violence is associated with a range of adverse physical and psychological health and social outcomes.
(1,4,5) In extreme 
cases, the violence results in the victim’s death. Between 40 and 70 per cent women victims of homicide are killed by a current or former spouse or partner, compared with between 4 per cent and 8 per cent male victims of homicide.
(4)Domestic violence
Gillian C. Mezey11.12

SECTION 11  forensic psychiatry 1982
Women who are abused by their partners over many years, often 
ﬁ nd it extremely difﬁ  cult to leave their partner and, even if they do 
leave, many women end up returning to the family home. There are a number of psychological and social reasons why many women ﬁ nd it difﬁ  cult to separate emotionally, as well as physically, from 
their violent partners. Learned helplessness,
(2) the progressive 
erosion of conﬁ  dence and self esteem cased by the abuse, feelings 
of guilt, shame and isolation, make it difﬁ  cult for victims to assert 
themselves, seek help, or even contemplate the possibility of an existence separate from their partner. For some women the abuse appears, paradoxically, to strengthen their emotional ties to the perpetrator, so-called ‘traumatic bonding’ .
(10) Women who try to 
leave abusive partners, experience signiﬁ  cant economic and social 
hardship, including lack of accommodation, inadequate ﬁ  nancial

hardship, including lack of accommodation, inadequate ﬁ  nancial 
support, and difﬁ  culties in caring for the children, as well as a 
disruption caused to their family and social support networks. These difﬁ  culties, as well as the fear of being tracked down by their 
partner, are often so daunting, that many women end up returning to their homes, choosing an existence that is familiar to them, in preference to precarious survival elsewhere. It is clear that physical separation does not always end the violence; many separations result in an escalation of threatening and violent behaviour, includ-ing stalking
(11) and the risk of domestic homicide is greatest around 
the time, or shortly after, separation.
Domestic abuse is associated with increased rates of depression,

Domestic abuse is associated with increased rates of depression, 
suicidality, Posttraumatic Stress Disorder, alcohol and substance misuse, and dependence in victims of abuse, compared with the general population.
(12) The more severe and chronic the abuse, the 
greater the impact on the victim’s mental health and symptoms of depression and hypervigilance may persist, even after separation.
(2)
Where present, symptoms of mental illness must be treated 
appropriately. However, offering victims a non-judgemental sympathetic response, providing information about options avail-able to them, about the risks associated with staying, or going and providing information about community resources, including refugees and counselling facilities are likely to be more important for the victims than any speciﬁ  c ‘treatment’ .
(13)

(13)
In the absence of direct questioning by a health professional, which 
is conducted in a sensitive and non-judgemental way, women are unlikely to spontaneously disclose experiences of domestic abuse in the context of a health consultation.
(5,13)  Unless domestic abuse 
is identiﬁ  ed, then the risk cannot be properly assessed or commu-
nicated to the victim. Screening for domestic abuse in health settings appears to be acceptable to women and is also effective in terms of increasing rates of identiﬁ  cation.
(13)
The frequency, severity, and chronicity of the abuse must be 
taken into account in assessing and managing risk. Browne’s study,
(14) comparing battered women who had killed their partner 
with battered women who had not killed, identiﬁ  ed the following

with battered women who had not killed, identiﬁ  ed the following 
risk factors for domestic homicide: frequency of violent assaults; presence and severity of injuries; alcohol intoxication or substance misuse in the perpetrator, threats to kill, sexual violence, suicidal ideation (in the victim), and access to a weapon. Campbell
(15) also 
identiﬁ  ed the following risk factors in a study of 220 cases in which 
women had been killed by violent partners: unemployment (male), choking, abuse during pregnancy, threats or harm to the child, the presence of a stepchild in the home, and separation. Morbid

women had been killed by violent partners: unemployment (male), choking, abuse during pregnancy, threats or harm to the child, the presence of a stepchild in the home, and separation. Morbid 
jealousy in the perpetrator and stalking behaviours are also more common in lethal, compared with non-lethal cases of domestic violence. Risk assessment must be carried out in all cases of domestic violence and communicated to the victim, to allow her to make informed and safe choices.
Conﬁ  dentiality and domestic violence
The primary consideration for the health professional should be 
the safety of the victim and any affected children. In general, the victims consent should always be sought prior to sharing informa-tion with others. A breach of conﬁ  dentiality, without the victim’s

knowledge, or consent, could increase the risk she faces and may discourage further disclosures to health professionals. The legal framework varies in different countries but in the United Kingdom, health professionals should be guided by the Data Protection Act (1998) and by principles on information sharing and good prac-tice, as set out within GMC
(16) and Royal College of Psychiatrists(17)
guidance. The Crime and Disorder Act (1998) allows for informa-tion to be passed on, in the absence of consent, in cases where the courts request information about a speciﬁ  c case or if the health 
professional judges there to be a signiﬁ  cant risk of harm to the 
woman, her children, or to someone else if that information is not passed on. The health professional should always inform the woman if they intend to breach conﬁ  dentiality, they should prop-

erly record their reasons for doing so and they should only pass on the minimum information required to achieve their objective. Further speciﬁ  c guidance on sharing information in the context of 
domestic violence has recently been provided by the Home Ofﬁ ce.
(18)
Perpetrators of domestic violence
Studies of men who abuse their partners are difﬁ  cult to interpret, 
largely because of the difﬁ  culties in identifying and recruiting 
men who are representative of the population as a whole. There is little evidence that domestic abuse is primarily attributable to underlying mental illness in the perpetrator. However, personality proﬁ les of perpetrators indicate high rates of personality disorder,

as well as alcohol and substance misuse and jealousy. There are two main personality proﬁ  les described in a perpetrator of domestic 
violence. The borderline/emotionally dependent type tends to conﬁ  ne their violence to within the family, they tend to be extreme-
ly insecure, jealous, and dependent on their partner and the violence is often precipitated by actual or threatened separation. The antisocial/narcissistic offender, is violent both within the family and outside and their violence is often associated with 
alcohol and drug misuse and high rates of criminality.
(19,20)
Group treatment programmes, aimed at changing the behaviour 
of men who batter, have had a degree of success in reducing violence.
(21,22)  However the evidence is limited and results are hard

(21,22)  However the evidence is limited and results are hard 
to interpret, given the fact that many men, arguably those who are at highest risk and who most need behaviour changing, are least likely to seek help or to remain in treatment. Treatment appears to be most effective when men are mandated through the Courts. Elements of such programmes include: encouraging men to take personal responsibility for their violent behaviour; increasing their awareness of the dynamics involved in the use of violence in relationships; challenging attitudes and beliefs around the use of

1983
violence in relationships between men and women; and developing 
skills for relating non-violently to others. Perpetrators of domestic abuse are encouraged to accept responsibility for the violence and to consider the consequences of their violence and the gains and losses it entails. Some perpetrators may need to learn particular skills to manage situations where they may previously have resort-ed to violence. It is important that any treatment programme of perpetrators monitors the effectiveness of the programme through maintaining constant contact with female partners in order to conﬁ  rm whether participation is having the desired effect and, 
more importantly, is not endangering them further.
Roberts, G., Hegarty, K., and Feder, G. (2006). Intimate partner abuse and 
health professionals. New approaches to domestic violence . Churchill 
Livingstone Elsevier, London.
Taket, A. (2004). Tackling domestic violence: the role of health professionals .

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6. Lewis, G. and Drife, J. (2004). Why mothers die 2000-2002. Conﬁ  dential 
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childhood sexual and physical abuse and risk of re-victimisation in 
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conﬁ dentiality . CR85. Royal College of Psychiatry, London.
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offenders: characteristics and offending needs . Home Ofﬁ  ce, London, UK.
20. Holtzworth-Munroe, A. and Stuart, G.L. (1994). Typologies of male 
batterers: three subtypes and the differences among them. Psychological 
Bulletin ,116, 476–97.
21. Gondolf, E.W. (2000). Re-assault at 30 months after batterer 
programme intake. International Journal of Offender Therapy and 
Comparative Criminology ,44, 111–28.

22. Morran, D. and Wilson, M. (1994). Confronting domestic violence: an 
innovative criminal justice response in Scotland. In Penal theory and 
practice: tradition and innovation in criminal justice  (ed. P . Dobash). 
Manchester University Press, Manchester.11.12  domestic violence

11.13
The impact of criminal 
victimization
Gillian C. Mezey and Ian Robbins
The prevalence of crime depends on the methodological approach 
that is adopted, the questions being asked and the population being surveyed. Crime ﬁ  gures are also affected by the willingness, or 
unwillingness of individuals to declare themselves as victims. This is particularly the case with ‘sensitive’ crimes, such as domestic and sexual violence. Not surprisingly, the self completion phases of the British Crime Surveys have been more effective in identifying such experiences than standard survey methodology. In addition, not all violence is necessarily recognized as a crime, and similarly not all crimes are necessarily deﬁ  ned as such, by their victims. Occasionally, 
violence may occur by mutual consent.
In the UK the British Crime Survey is regarded as the most

In the UK the British Crime Survey is regarded as the most 
reliable and comprehensive data source on criminal victimization, providing information about the extent of crime, as well as trends in the frequency and patterns of crime and changes in public atti-
tudes to crime over the years. The British Crime Survey for 2005–
2006 found there were approximately 10.9 million crimes against adults living in private households.
(1) Not all individuals in the 
population are at equal risk. Most crime differentially targets and damages individuals who are poor, disempowered, and marginal-ized within society. The risk of victimization is highest for divorced single or separated individuals between the ages of 16–24. Men are at greater risk of experiencing violent crime than women, except in the categories of domestic violence and sexual assault, where women are more at risk.
(2) Women are more vulnerable to domes-

tic violence and younger people are more at risk of crime than elderly people. Alcohol is also involved in a signiﬁ  cant number of 
violent offending both offenders and victims having been found to be inebriated or to have recently consumed alcohol at the time of the offence.
(3) Severe mental illness also appears to be a risk factor 
for crime victimization. In her study of 936 patients with severe mental illness living in the community, T eplin
(4) found that over 
one quarter of them had experienced violent crime in the past year, a rate more than 11 times that of the general population, even after controlling for socio-demographic variables.
Criminal victimization can have profound psychological and

Criminal victimization can have profound psychological and 
emotional effects, with the impact of violent (including sexual) victimization being greater than property or non violent offending. The experience of crime and the perception of crime as possible or probable, also has an impact on the individual’s fear of crime, and on their lifestyle. Women and the elderly are most fearful of 
crime, even though, in reality, young men are at greater risk. This may be because of the greater perceived adverse consequences of victimization and greater vulnerability in women and elderly people.
(5)
General effects of victimization
The experience of victimization can leave the individual feeling ‘diminished, pushed down, exploited and invaded’ .
(6) Victims

(5)
(6) Victims 
are often describe feeling stigmatized and isolated and unable to communicate their distress or feelings of vulnerability. Although friends and relatives may initially be supportive, such support may begin to fall away if the victim fails to recover within a reasonable period of time.
Social support and gender are important predictors of psychiat-
ric problems, including PTSD, in crime victims.
(7) Andrews et al.(8)
found that, women were more likely to receive negative responses 
from family and friends following violent crime and also to have higher rates of PTSD at 6 months follow up. The beneﬁ  ts of posi-
tive social support and impact of negative social responses were greater for women victims than men. Negative support was predic-tive of PTSD in both men and women, although this effect was more pronounced in women.

Immediate and short term effects of crime
High rates of dissociative symptoms are reported by victims of violent and sexual assault in the form of numbing, reduced awareness, derealization, and depersonalization, at the time of the crime.
(9,10) Dissociation may have immediate survival value, in 
terms of reducing the victim’s sense of immediate threat and mini-mizing the pain. However, it may also interfere with the individual’s longer-term recovery. Peri-traumatic dissociation at the time of the offence has been found to predict post-traumatic stress disorder development in women victims of violent and sexual assault.
Dissociative symptoms are part of the diagnostic criteria for 
Acute Stress Disorder which is a risk factor for the development of Posttraumatic Stress Disorder. Brewin et al.
(11) found that a diag-

nosis of Acute Stress Disorder at one month post trauma, predicted 83 per cent of post-traumatic stress disorder cases at 6 months follow-up. Acute Stress Disorder may be experienced during or

1985
immediately after a trauma and should resolve within four weeks 
of the conclusion of the traumatic event.
Long term psychological effects
Most crime victims are able to resume normal functioning and health, following a transient state of disequilibrium, without the need for medical or psychological intervention. However, some victims go on to develop chronic and persistent psychological or psychiatric problems.
(12) This may include increased rates of 
depression, anxiety and substance misuse. Recovery following criminal victimization is largely dependent on how the victim processes and makes sense of what has happened, whether the act can be accommodated into an existing frame of reference or whether the experience is so overwhelming and outside ordinary everyday experience as to render them incapable of reaching some kind of resolution.
Amongst crime victims, victims of violent crime have higher

Amongst crime victims, victims of violent crime have higher 
rates of psychological disturbance than victims of property crime who, in turn, have higher rates of disturbance that non victims.
(13,14,15)  Perception of life threat, physical injury and 
completed rape are associated with particularly high rates of PTSD.
(14,16,17)
Many of the psychological responses exhibited by victims and 
witnesses of crime ﬁ  t within a post-traumatic stress disorder frame-
work. In a study of 391 women victims, 27 per cent of all crime victims developed post-traumatic stress disorder.
(18) Although 
most victims of crime show substantial improvement up to 9 months after the offence, very little spontaneous recovery occurs thereafter
(19,20) and for some victims the effects are profound and 
long lasting.(18)
Physical health effects of crime

In general, people who have experienced crime have a poorer perception of their physical health and physical functioning and experience more chronic medical conditions than non victims. Physical and sexual assault are associated with increased cigarette consumption, alcohol and other drug abuse, self neglect, risky sexual behaviour, and eating disorders.
(21) Shepherd and 
Farrington(22) have suggested that a young man from a deprived 
urban area may suffer 60 years of incapacity as a result of injury, reduced quality of life, and self esteem. Increased crime rates are found in poorer areas, which means that the negative impact of crime on physical health may be difﬁ  cult to disentangle from the 
negative impact of poverty and deprivation on physical health.
Responses following speciﬁ  c criminal acts
(a) Murder

(a) Murder
The act of murder has profound effects, not just on the individual 
victim, but also on the friends, family members and acquaintances who are left behind and who are sometimes referred to as the ‘secondary victims.’ The act of murder is shocking in its ﬁ  nality and 
irrevocability, and the responses of survivors are both qualitatively and quantitatively different from the normal grieving process.
(23,24)
Rock(25) has suggested that it is not just the death itself, but the 
manner of death and its social meaning that is so devastating for those who are left behind. Unlike a ‘natural’ death, survivors are unprepared for their loss, there can be no anticipatory mourning, no reconciliation, and no proper leave taking. Many survivors describe feelings of stigmatization, isolation, shame, and betrayal,

but feel unable to communicate their distress or to connect emo-tionally with fellow beings. They often feel marginalized by the criminal justice system, with little access to information and they are burdened with having to cope with the inevitable, legalistic bureaucracy and the practical demands of life during a period of acute distress and emotional turmoil. In cases where the perpetra-tor and the victim are members of the same family, the survivors may experience particularly intense feelings of guilt and conﬂ  icting 
emotions.
The effects of violent traumatic bereavement on the secondary 
victims include physical health problems, cognitive impairment, and psychological effects, including posttraumatic stress disorder, depression, phobic avoidance, and impaired work and social functioning.
(26,27) Female gender and losing a child predict worse 
psychiatric outcome.(27) Survivors of homicide, tend to manifest

psychiatric outcome.(27) Survivors of homicide, tend to manifest 
both trauma symptoms and symptoms of grief, phenomena, with either predominating or appearing intermittently.
(28) This has lead 
to a proposed new diagnostic category of ‘traumatic grief’ , which contains two core components; trauma and of loss.
(29)
(b) Rape and sexual assault
The deﬁ  nition of rape varies across countries and between states 
within countries. In the UK, prior to 1994, the deﬁ  nition of rape 
was restricted to penile penetration of the vagina, with other forms of non consensual penetrative sex being deﬁ  ned as indecent assault. 
However, in 1994, the deﬁ  nition of rape was extended to include 
non consensual anal intercourse, thereby recognizing male rape victims for the ﬁ  rst time. The 2003 Sexual Offences Amendment 
Act further broadened the deﬁ  nition of rape to include penetration

Act further broadened the deﬁ  nition of rape to include penetration 
of the mouth as well as penetration of the vagina or anus by the penis. It also introduced three new measures on the issue of con-sent: ﬁ  rst, that a person can only consent to sexual relations if they 
have the freedom and capacity to make that choice, second, that all the circumstances at the time of the offence must be considered in determining whether the defendant is reasonable in believing the complainant consented and third, that individuals will be consid-ered most unlikely to have agreed to sexual activity if they were subject to threats or fear of serious harm, if they were unconscious, drugged or abducted, or if they were unable to communicate because of a physical disability.
In the majority of cases of rape, the perpetrator is known to

In the majority of cases of rape, the perpetrator is known to 
the victim and in many cases, the rapist is the current or former husband or partner.
(30) In spite of the seriousness of the offence, 
the British Crime Survey(30) found that only 60 per cent women 
who had been subjected to rape or serious sexual assault had told anyone about it and only around one in seven cases had been reported to the police. Reasons women gave for not reporting include: fear of reprisals, fear of public identiﬁ  cation, fear of 
appearing in Court and having to give evidence and lack of conﬁ  -
dence in the legal system.
(31) There is some evidence suggesting 
that women who proceed with prosecution following rape do worse, in terms of social adjustment and self esteem at one year follow up than women who decide not to proceed.
(32) Whether this

(32) Whether this 
is because Court proceedings delay or slow down the process of psychological recovery following rape, or because the legal process and particularly the experience of being cross examined in Court, represents a form of ‘secondary traumatization’ , is not entirely clear. If women do proceed with the Criminal Justice process, however, 11.13  the impact of criminal victimization

SECTION 11  forensic psychiatry 1986
preparing them for the experience, providing them with appropri-
ate information beforehand and giving them the opportunity to exercise choice, can help to offset the potentially de-stabilizing and distressing impact of criminal proceedings. Ultimately, the attitude taken by the police and the way the victim feels they have been treated appears to be more important in determining their psychological adjustment and satisfaction with the process, than the actual verdict.
(32)
About one-third of women who report rape develop long term 
psychological and social problems. These effects tend to be more severe and chronic than following non sexual violence.
(33,34) Rape 
trauma syndrome was ﬁ  rst described in the 1970’s(35) and was

trauma syndrome was ﬁ  rst described in the 1970’s(35) and was 
subsequently superseded by Posttraumatic Stress Disorder. Posttraumatic stress symptoms are generally present in the days and weeks following the assault, but then spontaneously resolve in the majority of cases. For some victims, however, the condition may become chronic and persist for many years, if left untreated.
(36)
Higher rates of depression, suicidal ideation, generalized and phobic anxiety, alcohol and drug dependence and sexual dysfunc-tion as well as physical health problems are also found in rape victims compared with non rape victims.
(37–41). Women who have 
been raped often describe problems in relationships, with excessive dependence, inability to trust and loss of conﬁ  dence and self 
esteem. Similar responses have been described with male victims of sexual assault.
(42)

(42)
The characteristics of sexual assault that predict long term 
mental health problems are: being the victim of a completed rape, being injured and the perception of a threat to life.
(14) Other pre-
dictors of long term disturbance include; prior psychological and social problems previous victimization, particularly childhood abuse past psychiatric illness, drug or alcohol misuse and lack of a supportive network.
Psychiatric treatment may be required for individuals who

Psychiatric treatment may be required for individuals who 
develop serious psychological problems following a sexual assault. It is probably inappropriate to embark on psychiatric treatment too early, because of the natural tendency for symptoms to resolve spontaneously in the weeks and months following the assault. Unless symptoms have resolved by 6 months, however, they are unlikely to resolve spontaneously thereafter without some form of psychological intervention or psychiatric treatment (see Chapter 4.6.2)
There is no evidence that counselling is effective in alleviating 
short term distress or in preventing the development of long term psychiatric disability in rape victims. Indeed recent studies have suggested that counselling may even be harmful, if carried out by inadequately trained and supervized individuals.
(43) Many of

(43) Many of 
the key organizations working with victims e.g. Victim Support, emphasize their role as supporters and befrienders and they provide both practical assistance, such as accompanying victims to identiﬁ  cation parades, helping with paperwork and compensation 
claims, as well as offering emotional support following the assault and through any subsequent criminal proceedings. Rape victims are most likely to beneﬁ  t from services that are co-ordinated, inte-
grated and streamlined.
(43) An example of this in the UK has been 
the development of Sexual Assault Referral Centres (SARCs), which provide a ‘one stop shop’ of medical, counselling, legal and forensic services for victims of sexual assault. Evaluation of these centres and in particular the beneﬁ  ts for victims and the Criminal Justice 
System, is ongoing.(c) Burglary and robbery

The effects of burglary are generally less severe and long lasting than following violent and ‘contact’ crimes although some victims may develop chronic mental health problems, including Posttraumatic Stress Disorder.
(18) Repeat victimization is especially 
common in the case of burglary and second or subsequent burglar-ies are more likely to have a greater long term impact. Repeated experiences of burglary may lead to victims of burglary taking additional security precautions or even moving house in order to restore a sense of safety and control over their lives.
(44) Individuals 
living in areas of poverty and deprivation and single parent fami-lies are most vulnerable to burglary. Robbery, unlike burglary involves not only direct contact between the victim and the perpe-trator, but also implies a degree of life threat and is therefore more likely to precipitate post-traumatic psychiatric illness, including post-traumatic stress disorder.

(45)
(d) Workplace violence
Violent assaults in the workplace have increased in frequency and severity in recent years.
(46–48) Budd et al.  found that working at 
night was the only signiﬁ  cant factor which predicted its occurrence. 
There was a clear relationship between workplace violence and increased job stress, reduced job satisfaction, increased likelihood of looking for a new job, as well as bringing weapons to work Kopel & Friedman
(49) found that police ofﬁ  cers witnessing incidents 
of violence reported intrusive thoughts and images, and used avoidance to deal with the intrusive phenomena. Whilst recogniz-ing that avoidance is a feature of post-traumatic stress disorder, they also suggest that denial and avoidance are part of the culture in male-dominated occupations such as law enforcement agencies. Miller-Burke et al.
(50) found that most employees who had experi-

enced robberies had multiple adverse consequences. Psychological functioning, physical wellbeing, social and occupational function-ing were all impaired. Having been involved in more than one incident was associated with more severe outcomes.
In the United States Hewitt and Levin
(51) point to the high rates 
of occupational assaults among health-care workers. Whilst fatal workplace assaults are more likely to involve males in the course of robberies, women were more likely to be involved in non-fatal workplace assaults, with health-care workers being most affected. The rate for health and social care workers was 10 times that of private non-health care industries. Williams
(52) found that 26 per 
cent of nurses reported physical assault while at work. This rate of assault is similar to that found by O’Connell and Bury
(53) who

(53) who 
carried out a survey of all general practitioners in the Eastern Health Board of Ireland. They had a 98 per cent response rate which revealed that 21 per cent of general practitioners had experi-enced violence or aggression although in only 7 per cent of the incidents reported did it result in injury. Not surprisingly there is a strong inverse relationship between workplace assaults and job satisfaction.
(e) Child and adolescent victims of crime
Children and young people are especially vulnerable to crime and victimization, in particular by people they know and are dependent on, although stranger violence is a small but important problem.
(54)
The 1992 British Crime Survey(55,56)  looked at the victimization

(54)
The 1992 British Crime Survey(55,56)  looked at the victimization 
of young people away from the home and reported that about one-third of 12 to 15 year olds had been assaulted in the last 6 to 
8 months. This would compare with a rate of around 1 per cent in

1987
adults. Most of these assaults happened at or near school and were 
committed by a sole perpetrator who was known to the victim. The survey also identiﬁ  ed high rates of fear of crime amongst adoles-
cents, with girls being more fearful than boys. A range of mental health problems have been identified following victimization within the child and adolescent population.
(57)
Hate crimes
The deﬁ  ning characteristics of a hate crime is that the individual 
victim is targetted because of bias or prejudice, based on their actual or perceived social grouping or ethnicity, sexual orientation, religion or political orientation. Herek et al.
(58) suggest that a 
signiﬁ  cant proportion of lesbians and gay men who had been 
assaulted believed that their sexual orientation had been a motivat-ing factor. One-quarter of men and one-ﬁ  fth of women said that 
they had experienced victimization because of their sexual orienta-tion. When compared to other crime victims, they had signiﬁ  cantly

they had experienced victimization because of their sexual orienta-tion. When compared to other crime victims, they had signiﬁ  cantly 
more symptoms of depression, anxiety and PTSD as well as more crime related fears and a lower sense of mastery. Rose & Mechanic
(59)
reported that 73 per cent of lesbians and gay men had experienced at least one homophobic attack. Victims of homophobic violence had more PTSD symptoms than did victims of other homophobic crimes or non victims although there was no signiﬁ  cant difference 
in rates of depression. They also found that homophobic sexual assaults were more likely to involve known assailants, and multiple perpetrators and more likely to be repeated.
Hate crimes tend to be under-reported to the police, the psycho-

logical effects tend to be long lasting, and have a negative impact not only on the individual victim, but also on the community. It has been argued that hate crimes require policy directed to addressing the causes rather than simply dealing with the needs of individual victims. Black and ethnic minority individuals appear 
to be particularly vulnerable to criminal victimization and in 
a proportion of these cases the offence is considered to be ‘racially motivated’ . 
(60,61). Around one in six of all incidents of criminal 
victimization against Asians and African-Caribbeans are consid-ered to be racially motivated
(61) and, regardless of the type of 
offence, ethnic minority victims tend to report higher levels of worry about crime then white victims.
(60) Fear of crime appears

(60) Fear of crime appears 
to be particularly high amongst Bangladeshi and Pakistani indi-viduals, who are also most likely to describe their victimization as racially motivated. It has been suggested that victims who perceive their victimization to be racially motivated, experience more serious and persistent psychological effects that individuals who did not consider racism as a motivation.
(g) Terrorist crimes
A number of studies have looked at the impact of terrorist attacks which, whilst relatively infrequent, in comparison to other crimes, have a considerable political and social impact. Whalley and Brewin
(62) reviewed the mental health effects of terrorist attacks

(62) reviewed the mental health effects of terrorist attacks 
on the direct victims, as well as on the general (non affected) population. In the general population, symptoms of distress and stress are high in the ﬁ  rst few days following an incident, but tend 
to resolve spontaneously so that, although PTSD is found in between 11 per cent-13 per cent of the general population, in the ﬁ rst six weeks following a single terrorist attack, this falls to below 
3 per cent after 8 weeks. Factors such as previous adversity, pre-existing mental health issues and membership of minority groups may increase vulnerability to the impact of terrorism. PTSD is the most common psychiatric disorder in direct victims of terrorist 
attacks, followed by depression although other problems such as traumatic grief, panic disorder, phobias, generalized anxiety and substance misuse have also been reported.
(63) Most studies have 
reported that between 30–40 per cent of those closest to the site

reported that between 30–40 per cent of those closest to the site 
of the attack, will develop a psychiatric disorder within 2 years. However, the majority of direct victims have no contact with men-tal health professionals. In the aftermath of the September 11th attacks in New Y ork only around one-quarter to one-third of those suffering from PTSD were in receipt of treatment. Whalley and Brewin
(64) suggest that a focused outreach approach such as 
a ‘screen and treat’ programme may be needed to identify those with signiﬁ  cant impairment and help them to access evidence 
based treatments.
The extent of physical injury during a terrorist attack is the best 
predicator of post-traumatic stress disorder rates both in the short term
(65) and many years after the event,(66) although it does not

(65) and many years after the event,(66) although it does not 
predict the development of a depressive illness. Studies which have looked at the impact of shootings tend, by their very nature to be small scale, but have found signiﬁ  cant levels of distress and 
high rates of post-traumatic stress disorder and other psychiatric disorders.
(67) Being held hostage has also been related to high levels 
of distress both in victims and their families.(68) Where captivity 
has occurred, there may be strong attachment and paradoxical gratitude towards the captors with positive emotions including compassion and identiﬁ  cation with the terrorist’s values, often 
described as the Stockholm syndrome.
Support services and treatment 
There are so few culturally accepted rituals of support for victims

There are so few culturally accepted rituals of support for victims 
of crime, that it often becomes the task of the therapist to normalize the process. In the United Kingdom victim support schemes offer practical assistance, for example accompanying the victim to identiﬁ  cation parades and court hearings, completing Criminal 
Injuries Compensation Board forms, as well as providing support and reassurance following crime. Referrals to the schemes are generally made by the police, but are occasionally accepted from involved professionals or from the victims themselves. However, victims of serious crimes, such as sexual assault or physical vio-lence, and the families of murder victims may develop psychiatric illness, which requires referral to mental health servic es for specialist 
Treatment approaches are drawn from a variety of paradigms

Treatment approaches are drawn from a variety of paradigms 
including cognitive behavioural, psychodynamic, psychosocial, and 
pharmacological treatments, and are often trauma focused in gen-eral rather than being speciﬁ  c to problems associated with criminal 
victimization. Ochberg (6) categorizes them into two main approaches, the ﬁ  rst focuses on previous personality and attributes 
mental health problems and difﬁ  culties in adjustment following 
crime to pre-existing unresolved issues and weaknesses, rather than to the traumatic events. The second approach focuses more on the 
events themselves, the individual strengths and coping styles of the 
victim and setting realistic achievable goals.
In the UK the 1998 Crime and Disorder Act placed an obligation

In the UK the 1998 Crime and Disorder Act placed an obligation 
on the NHS to work in partnership with the Police and Local Authorities in dealing with the consequences of crime. Many peo-ple who present to the NHS for treatment following violent crime 11.13  the impact of criminal victimization

SECTION 11  forensic psychiatry 1988
do not present to the Police or criminal justice agencies. As many of 
the services for crime victims are organized by or accessed through the criminal justice system these people are likely to miss out on services. There is a clear need for a direct relationship between the NHS and criminal justice agencies in the way in which treatment is provided and its relationship to the criminal justice processes but as yet, other than in a small number of speciﬁ  c projects it does not 
happen.
Often immediately following victimization help is offered and

happen.
Often immediately following victimization help is offered and 
family and friends rally round. This may not be the time when most people need formal psychiatric help. The majority of people post assault experience sympotms of PTSD and other psychiatric problems but also the majority improve spontaneously even in the case of serious crimes such as rape. The question comes as to when to intervene. The National Institute for Clinical Excellence (NICE, 2006) recommend a position of watchful waiting and if in the ﬁ  rst 
month(s) symptoms are not improving or indeed may be increas-ing then treatment is indicated otherwise waiting and monitoring to identify who will not spontaneously improve is the approach of choice.
Previous work had already shown that timing of appropriate 
services is important. Shepherd et al.
(62) have shown that while

(62) have shown that while 
accident and assault victims have similar levels of depression and anxiety in the immediate aftermath three months later the assault victims have higher levels of symptoms. In the immediate after-math of criminal victimization it has been suggested that having the opportunity to talk may reduce later symptoms Where there have been speciﬁ  c RCTs of immediate intervention they have not 
shown themselves to be particularly effective. Rose, Brewin, Andrews and Kirk
(63) compared an education intervention with 
education plus psychological debrieﬁ  ng or an assessment only con-
dition in a randomized controlled trial. They found that while all groups improved over time there were no signiﬁ  cant differences 
between groups. This is hardly surprising when considering the result of Rose, Bisson & Wessely
(64) who carried out a systematic

(64) who carried out a systematic 
review of RCTs examining the impact of debrieﬁ  ng. They found 
11 RCTs of which six showed no effect at all, three had a positive effect and two had a negative outcome.
This has led to a belief that there is no point in any immediate 
interventions but this ignores the contribution made by organiza-tions such as Victim Support or Rape Crisis centres. They do not offer formal therapy but rather give information, offer the oppor-tunity to ventilate emotions, practical help and assistance in mak-ing compensation claims or participating in the criminal justice system. Shepherd and Bisson
(65) who make the case for more inte-
gration between health services and other agencies describe the two models of Victim Support interventions which are initiated within the NHS and address the needs of victims which would otherwise be overlooked.

In terms of formal psychological therapies and in the longer term 
Cognitive Behavioural Therapy has been used with great effective ness. 
Ehlers & Clark
(66) reviewed the use of CBT in early interventions. 
They concluded that CBT was superior to supportive counselling but that brief CBT in the ﬁ  rst month showed no superiority over repeat-
ed assessments. Where longer programmes ie 16 session were offered in the ﬁ  rst 4 months they found that CBT was superior to supportive 
counselling, repeated assessment or no intervention at all.
There have been a number of other empirical studies demon-
strating the effectiveness of structured cognitive behavioural approaches to treating established PTSD, which are discussed further 
in Chapter 4.6.2

The impact of crime on the individual victim is profound but is frequently underestimated by mental health professionals. Wide-ranging personal, social, and economic consequences could be prevented if a range of appropriate interventions were available. Most post traumatic stress treatment programmes in the United Kingdom have developed in response to speciﬁ  c disasters, which

may not be relevant to or as effective with crime victims. In order to provide appropriate treatment to crime victims, mental health professionals need to recognize the importance of active interagency liaison with the police, the courts and with voluntary organizations such as victim support schemes. Crime victims tend to be relatively invisible and disempowered; they are less likely to be supported by active campaigning groups than survivors of major disasters and, because of associated feelings of shame and stigmatization, they 
may be reluctant to claim their entitlement to proper care and

may be reluctant to claim their entitlement to proper care and 
treatment. The fact that their plight is often used as a political foot-ball is likely to reinforce feelings of helplessness and insecurity. Given its prevalence, crime represents both an ordinary and an extraordinary event; it is likely to affect everyone at some point in their lives and the fact that most crime victims recover from the experience should not deprive those who need it, to proper care.
Garcia-Moreno, C., Jansen, H., Ellsberg, M., et al.  (2005). Multi-country 
Study on Women’s Health and Domestic Violence against Women WHO, Geneva. 
Krug, E., Dahlberg, L., Mercy, J., et al.  (2002). World Report on violence and 
health . WHO, Geneva.
For general information about victims, policy, statistics and support 
provision www.homeofﬁ  ce.gov.uk/crime-victims
Hearing the Relatives of Murder and Manslaughter Victims. Consultation. 
D.C.A.;London. Sept 2005 www.dcs.gov/manslaughter/manslaughter.

pdf
Domestic Violence, Crime and Victims Act (2004) www.opsi.gov.uk/ACTS/
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817–26.

‘Prediction is very difﬁ  cult, especially about the future’
Niels Bohr (1885–1962)
Assessing and managing the risk of our patients being violent 
towards others now occupies a prominent position in virtually all forms of mental health practice, but it remains a contentious area. At the highest level researchers, psychometricians, and statisticians argue about almost every aspect, even whether anything useful can be said about individual outcomes rather than group indicators. At the next level an industry ﬂ  ourishes of selling training, and risk 
assessment tinstruments, to those who then appear as experts in a wide range of mental health and criminal justice contexts. On the ground, almost everyone in mental health is drawn into ﬁ  lling out

purpose-designed forms and complying with protocols, most of little or no demonstrated validity. This chapter is intended to make clinicians aware of both the possibilities and limitations of existing approaches to the assessments of risk. Given that there is no reason for mental health professionals to evaluate risk without gaining information to manage it, this chapter will also address the management of risk for aggression and violence.
Constructing risk
A critical analysis will be attempted of how risk has come to be constructed in our society and how this is impacting on mental health and criminal justice. When an approach is adopted which attempts to reveal the foundations and historical evolution of a widely accepted social construct, like risk, there is a danger that it will appear overly sceptical or even mocking. It is important to emphasize at the outset that:
1 The assessment of the probability of patients behaving in

1 The assessment of the probability of patients behaving in 
ways damaging to others and the management of that risk is a legitimate clinical activity.
2 That attributions of levels of risk to a patient occurs in a social 
and cultural context and is inescapably a construct.
The discourses around the dangerousness of the mentally ill have 
gradually been replaced by those of risk. This change is usually pre-sented as a product of the progress of knowledge and the improved conceptualization of that knowledge.
(1–4) The language of

(1–4) The language of 
danger transmuted into the language of risk also emphasizes the probabilistic nature of risk assessment. We are not now and prob-ably never will be in a position to be able to determine with certainty who will or will not engage in a violent act. Relying on a range of empirically supported risk factors, though, we can makes a reasoned determination of the extent to which those we are assessing share factors that have been found in others to relate to an increased level of risk. Risk embodies the interaction of a range of factors, which are not necessarily dangerous in themselves, such as age, gender, marital status, ethnicity, employment status and, of course, mental disorder.
(5) Risk factors can be any variables

(5) Risk factors can be any variables 
which are statistically associated with a future violent episode or event. There is no assumption of causality linking the predictor to the predicted.
Risk assessment came relatively late to the mental health ﬁ  eld. 
Not until ‘harm to others’ or ‘undue risk’ became criteria for invol-untary hospitalization and forensic detention did ‘dangerousness’ of patients assume the spotlight. The focus on risk ﬁ  rst surfaced in 
Western Societies in the 1970s in the context of concerns about damage being inﬂ  icted on individuals by the actions, or inactions, 
of corporate and governmental agencies. These concerns fed the emergence of widely based environmental movements as well as an escalating number of class actions and individually driven litigations. Under the banner of risk a new blaming system emerged 
of which Douglas
(6) writes ‘we are . . . almost ready to treat every

(6) writes ‘we are . . . almost ready to treat every 
death as chargeable to someone’s account, every accident as caused by someone’s criminal negligence, every sickness a threat-ened prosecution. Whose fault? is the ﬁ  rst question . . . then what 
damages? what compensation? what restitution . . .’ (pp. 15–16). One response to this culture of blame has been the emergence of what O’Malley
(7) refers to as a new prudentialism in which individuals, 
professionals and corporations, increasingly held responsibility for the impact of their actions on others, resort to risk management strategies in which risk is assessed, managed, insured against, and where possible removed.
Psychiatrists and psychologists are among those who have

Psychiatrists and psychologists are among those who have 
become caught up in the ‘culture of blame’ . Any damaging or dis-tressing occurrence which is experienced by, or caused by, someone who is, or has been, a patient of the mental health services, is transformed into a preventable tragedy for which professionals are Assessing and managing the 
risks of violence towards others
Paul E. Mullen and James R. P . Ogloff11.14

SECTION 11  forensic psychiatry 1992
to be held responsible. Rose(8) suggests the new imperatives of risk 
assessment and risk management operate to establish mechanisms to control mental health professionals which through standards, audits and enquiries not only regulate professionals but hold them personally responsible for unwanted outcomes. Douglas (6) argues ‘probability analysis arrives at politics in the form of a word ‘risk’ . . . the word gets its connection with probability squeezed out of it and put to the same primitive political uses as any term for ‘danger’’ (p. 48). Risk assessment and risk management are concepts which have the potential to shift blame towards clinicians who have failed to follow procedure and away from managers who fulﬁ  lled their

responsibilities by ensuring correct protocols were in place, irrespective of the possibility of the realistic application of such protocols. The language of risk can also shift the focus from politi-cians who determine resources and establish systems of care to those who fail to identify and manage risk in the individual case. Perhaps most importantly the increasing centrality of risk assess-ment potentially creates a vision of the mentally disordered as primarily embodiments of varying degrees of risk and the mental health services as agents in controlling and obviating the supposed danger to the community.
Assessing dangerousness used to be the almost exclusive 
province of the forensic mental health professional.
(9,10) It was a 
marginal activity based on arcane knowledge and assumed wisdom that only experience could provide.
(11,12)  Risk assessment and

(11,12)  Risk assessment and 
management in contrast have become central to current mental health practice in almost all its guises. It has become among the most important activities defining professional competence. Understanding the cultural, legal, and political roots of the increas-ing hegemony exerted by the rhetoric of risk over psychiatric prac-tice may demystify, but does not free the professional from the imperatives of operating effectively in this new environment. It seems so obvious, as to be self evident, that mental health profes-sionals are expected to consider the probability that their patient will act in a destructive manner and to act to prevent such harms. But the self evident is often the ideological unconsidered. It is not obvious that a mental health professional’s primary responsibility is to the wider community rather than their patient. It is not obvious that it is possible to effectively predict such risks as they

apply in the individual case. It is not at all obvious how we should 
act in the face of a prediction of risk, and it is certainly not obvious that such concerns should be a major determinant of our approach to patients.
Words are rarely innocent. Risk is not the same as probability,

for risk implies a degree of danger. Even those deemed to be at ‘low risk’ still appear to present some degree of danger. No one, it seems, is considered risk free. Risk management is not the same as harm minimization, for it promises a prevention of unwanted outcomes. Psychiatry deals with disorders which have both substantial morbidities and mortalities. Good management may reduce but cannot, in our present state of knowledge, prevent all such morbid-ity and mortality. Furthermore, reducing morbidity and mortality long term may only be possible at the price of accepting an increased probability of mortality in the short term. Suicide in prison, for example, can be prevented by isolating and observing vulnerable inmates in transparent plastic bubbles, bereft of features from which suspension is possible, or by the simple expedient of chain-ing them hand and foot to a bed (both strategies are in use today). If the only good is preventing self harm such draconian measures acquire

is possible, or by the simple expedient of chain-ing them hand and foot to a bed (both strategies are in use today). If the only good is preventing self harm such draconian measures acquire currency irrespective of the psychological damage and

abuse of basic human dignity involved. Moreover, as the aim has become removing all risk of suicide in prison, more and more vulnerable prisoners are being subjected to such restrictions and in many jurisdictions ‘witch hunts’ now regularly follow every death across jurisdictions. We cannot force the genie of risk back into the lamp. Mental health professionals will continue to be made publicly accountable. Professional self regulation is being replaced by statutory regulation and the ravages of civil litigation.
(13) As 
Rose(8) notes we will be forced to play a central role ‘in the strategy 
of reducing risk and minimizing harm under threat of sanction and within the disciplines imposed by a plethora of practices of blame’ (p. 18).
Contemporary approaches to risk 
assessment
It is no longer possible for mental health professionals to distance

It is no longer possible for mental health professionals to distance 
themselves from the process of risk assessment. Throughout the 1970s and 1980s mental health professionals were almost of one voice in proclaiming both their inability to predict dangerousness and the basic paciﬁ  vity of the mentally disordered.
(14) Despite this 
public stance dangerousness criteria came to dominate civil commitment, with courts simply ignoring arguments that the pre-diction of dangerousness was beyond the ken of psychiatrists and psychologists.
(15) In addition liability based on failures to predict 
dangerousness was established in landmark cases including those arising out of Poddar’s killing of Tarasoff
(16) and Hinkley’s attempt 
to assassinate President Reagan.(17) Last, but not least, the criminal

to assassinate President Reagan.(17) Last, but not least, the criminal 
courts increasingly suborned mental health professionals into predicting dangerousness in the pursuit of such sentences as preventive detention and death.
(15,18) In the US and the UK the 
emergence of the language of risk at the end of the 1980’s was in part a recognition of the centrality assumed by predicting and managing the potential for violence perceived by the public to reside in the mentally disordered. In the UK the public inquiry into the killing of Jonathan Zito by the psychiatrically disordered Christopher Clunis set a pattern for future homicide enquires.
(19)
Failures of risk assessment and management by individual practi-tioners, together with inadequacies of communication and service provision, were identiﬁ  ed as major contributors to ‘avoidable’ 
killings.
(19) Such developments set risk assessment at the very centre 
of the mental health agenda.

killings.
Given the challenges of risk assessment, what is the current state 
of knowledge and can it be of assistance to clinicians? The limited research available on ‘dangerousness prediction’ conducted in the 1970s showed that psychiatrists and psychologists had unaccept-ably low levels of accuracy in predicting which patients would go on to be violent in the future.
(20) It was found, perhaps not sur-
prisingly, that psychiatrists, psychologists, and release decision-makers tended to make conservative decisions that suggested that 
people were at risk for dangerousness or violence when, in fact, they were not. Similar ﬁ  ndings have been obtained over time. For 
example, Belfrage
(21) found that clinicians found 90 per cent of

(21) found that clinicians found 90 per cent of 
a group of 640 offenders sentenced to psychiatric treatment in Sweden to be at ‘risk of severe criminality;’ when, in fact, only 50 per cent went on to commit any kind of crime.
Reasons given for the errors made in risk prediction include 
clinicians’ confusion and lack of knowledge of valid risk markers

1993
and risk factors. In addition, as with other areas of decision-making, 
even if clinicians do have a reasonable understanding of risk fac-tors, it is difﬁ  cult to systematically consider them and to put togeth-
er a risk appraisal in a systematic way. Advances in risk assessment have included the identiﬁ  cation of an expanded range of predictor 
variables relevant to violence. Most important among these are those variables that are subject to change (i.e., they can change over time and they can be inﬂ  uenced by treatment or other interven-

tion). Generally speaking, risk assessment variables can be classed as ‘static’ (i.e., those that cannot be changed) and ‘dynamic’ (i.e., those that can change over time). Actuarial risk schemes, which will be discussed later in this chapter, are based upon variables that were measured from the past. These historic variables generally could not change over time. For example, if one began being vio-lent as a young person, that fact will not change over time. Dynamic variables, in contrast, are subject to change over time, sometimes rapidly. These variables include such things as state of mind, situa-tional factors, attitudes, plans, support, etc. Effective risk assess-ment must take into account both static and dynamic variables; however, risk management generally requires an understanding of the dynamic risk variables. Contemporary approaches to risk assessment and management take into account both static and dynamic variables, thus considering an individual’s past, present, and

of the dynamic risk variables. Contemporary approaches to risk assessment and management take into account both static and dynamic variables, thus considering an individual’s past, present, and future risk factors that might affect the likelihood of him or her becoming violent.

There has been considerable progress since Monahan
(20) ﬁ rst 
reported that psychologists and psychiatrists were essentially unable to predict risk to any acceptable extent. Current research shows that risk assessment approaches provide a level of accuracy that now far exceeds chance.
(22)
The limits on mental health professionals’ 
engagement in risk assessment
There are two legitimate perspectives on risk assessment:-
1 The clinician whose work involves considering patients’ levels 
of risk as part of a process whose purpose is primarily to improve the management of patients.
2 The forensic evaluator for whom risk assessment is a tool 
to improve the reliability of opinions provided to courts and tribunals charged with making decisions about an individual.
Forensic mental health professionals in the US and Canada tend

Forensic mental health professionals in the US and Canada tend 
to see their role primarily as evaluator. It is not uncommon for forensic psychiatrists and psychologists to primarily conduct assessments for the courts as their means of employment. This reﬂ ects the generally accepted separation of the assessment and 
treatment roles. In stark contrast in the UK and Northern Europe the clinician perspective dominates even for forensic specialists. Relatively few forensic clinicians would operate as court evaluators alone, though some like their US colleagues would try and separate the roles.
This chapter is written for mental health professionals in a

This chapter is written for mental health professionals in a 
wide range of contexts, not for forensic specialists. As a result the emphasis on this chapter will be on the clinical perspective. North American readers should, however, keep in mind that this perspective is not shared by many specialists in the forensic ﬁ  eld there who 
would consider it not just problematic but ethically questionable to 
mix the assessment and treatment roles.Boundaries need to be drawn around when, where and for what 
purpose, mental health professionals can ethically engage in assess-ing the probability of an individual committing violent or criminal acts. There are somewhat different constraints operating on clinicians than for those carrying out evaluations for the purpose of preparing reports for decision-making bodies like courts and tribunals.
The ethical and practical constraints on a clinician assessing risk 
entirely in service of effective treatment include:

1 Ensuring the assessment serves the interests of the patient in 
terms of improving management and protecting them from acts which will damage their interests. The seriously mentally ill when they become violent all too often target those who support and care for them thus destroying the relationships critical to their own social survival. In addition, criminal and violent acts of the sort usually associated with the mental disordered rarely, if ever, brings anything but increased problems for the patient. Thus, reducing the likelihood that the patient will engage in criminal and violent acts serves not only the public interest but also the patient’s interests.
2 Mental health variables (which include psychological variables

2 Mental health variables (which include psychological variables 
and personality traits) are a prominent feature of the individual’s clinical picture and are also of potential relevance to the proba-bility of future damaging behaviours.
3 Avoiding providing greater emphasis to risk than is necessary 
given the totality of the patients needs and vulnerabilities.
4 The assessment should wherever possible connect potential 
risk to those factors whose amelioration will reduce that risk. Ultimately a health professional can only justify engagement in risk evaluation if they lead to better outcomes for the evaluated as well as the community. Risk assessment ﬁ  nds its ultimate 
justiﬁ  cation in risk management.
5 Avoiding using risk and risk assessment to disqualify patients 
from access to the treatments they require. Increased risk requires increased therapeutic enthusiasm, not rejection.
(23)
6 That any concerns raised by a risk assessment are shared with

(23)
6 That any concerns raised by a risk assessment are shared with 
the patient and the proposed management strategies explained. Even unwelcome restrictions are resented less if the reason for their imposition is explained.
7 Retaining an awareness of the limitations of the predictive power 
of risk assessments and the need to ensure proportionality between the risk actually apprehended and any imposed remedy.
8 Ensuring a level of professional competence adequate to the task.
9 Making use, where possible, of the skills and knowledge of the 
multidisciplinary team in the assessment.
Those obligations on those engaging in risk assessment as part 
of an evaluation for a decision-making body are even more oner-ous and should include:-
1 The patient consents to the examination in the knowledge of

1 The patient consents to the examination in the knowledge of 
the nature of the assessment, the purposes to which it may be proffered, and the limitations on conﬁ  dentiality that may apply.
2 A reasonable body of empirical evidence exists to guide the risk 
assessment including, where possible, empirically validated structured risk assessment measures.11.14  assessing and managing the risks of violence towards others

SECTION 11  forensic psychiatry 1994
3 The risk assessment is conducted in consideration of the legal 
parameters governing the decision-making body (e.g., criteria to be considered for change of orders or release for forensic psychi-atric patients) while realizing that the legal questions to be answered never parallel the clinical or evaluative results mental health professionals can reasonably provide (e.g., there is no clinical parallel to legal criteria such as ‘undue risk’).
4 The assessment is based on a careful analysis of the relevant 
characteristics of the particular individual which in all but exceptional circumstances have been obtained in part by a direct examination of the individual.
5 The risks are expressed in terms of probabilities (not attributions

5 The risks are expressed in terms of probabilities (not attributions 
of dangerousness) with clear admissions of the fallibility and potential variability in the prediction. The problem should be acknowledged of employing risk factors derived from studies on populations from different cultures and contexts. After all nobody would use risk data from Los Angeles to calculate the car insurance premium for a driver in Dublin or Oslo without considerable caution.
6 Account is taken not just of the probability of damaging behav-
iour but the nature and severity of such conduct. Proportionality needs to be maintained between what is predicted and the response. It is all too easy to employ methods which establish increased risks of a wide range of unwanted behaviours only to ﬁ nd them used to justify draconian and punitive responses which 
would only be acceptable in the face of the imminence of serious violence.
7 The conﬁ  dence and certainty with which any prediction is for-

mulated to take account of the implications for the person being assessed. Risk predictions may be offered in terms of probabili-ties but they will almost always be used to justify all or nothing decisions.
8 That personal and professional integrity is strictly maintained. 
This is no simple matter when the evaluator is either in the pay of the patient, or of those whose interests are not necessarily those of the patient.
The potential conﬂ  icts generated when acting for a patient as

The potential conﬂ  icts generated when acting for a patient as 
both a professional evaluator and a clinician are so considerable that some experts argue that such a dual role is inherently unethical. They argue in preparing reports for decision-making bodies the interac-tion ceases to be that of health professional and patient, and becomes entirely that of expert, or ‘forensisist’ , and evaluated. The expert’s obligation is then not to the evaluated but to their own professional competence and the rules governing the process the report will serve (e.g., criminal court, family court, mental health tribunal).
In our view even in an encounter between a health professional

In our view even in an encounter between a health professional 
and a person purely for the purposes of an evaluation for a court there remains obligations to the person as patient [patient from the Latin for to suffer, who in this instance suffers the intrusions of an examiner who cannot for the evaluated entirely cast off the guise of physician or healer]. The solution is to learn to live with the contradictions and accept the dialectic between responsibilities to the patient and obligations to the agencies of society. The result of accepting the duality of the role inherent in assessing a patient’s risk of harming others does exclude participation in a process that could increase the risk to the patient of fatal (e.g., death penalty evaluations) or serious harm (e.g., sexual predator laws whose sole

purpose is justify a process of prolonging incarceration beyond the expiry of a sentence). It does however legitimate having the dual role of clinician and evaluator in some circumstances. In fact those who totally eschew ever taking on such a dual role, we believe, are at risk of deluding themselves that they can caste off the mantle of clinician for the patient, and become a socially neutral, objective, observer and reporter.
The dialectic between the demands of a professional responsible 
to the health of your patient and the demands of professional integrity and honesty owed courts and tribunals is almost always possible to resolve. T o fail to accept engagement with the conﬂ  icts 
which in reality usually exist for evaluators and clinicians reporting to external authorities is in our opinion an act of self deception in which you become an agent either of patient, or authority, and no longer an autonomous responsible professional.

Some situations make nonsense of the above considerations, 
notably death penalty hearings. One of us (J.O) has extensive expe-rience of working with those on death row, the other (P .M) only a comparatively slight acquaintance. We are both of the opinion, however, that it is impossible to honestly discharge your responsi-bilities as clinician, as evaluator, or as decent human being, in such circumstances.
Risk assessment approaches
There are ﬁ  ve basic approaches to evaluating the risk of violence:-
1 Probability models based on established risk factors. The risk 
factors can be derived actuarially from studies of particular populations (e.g. Violence Risk Appraisal Guide (VRAG) and Static 99) or rationally ascertained from the risk literature (e.g. Historical Clinical Risk 20 (HCR-20)).
2 Clinical experience based on recognizing previously encountered

2 Clinical experience based on recognizing previously encountered 
(personally or in the literature) patterns associated with future violence. The clinical approach is largely relevant to the avoid-ance of obvious errors like discharging morbidly jealous men who are threatening to kill their partner.
3 A mixture of 1 and 2 where the risk assessment instrument 
is employed to guide the appraisal of risk factors and clinical judgment is applied to balance idiographic information with the nomothetic variables as in the structured professional judgment approach of which the HCR-20 is the prime example.
(22)
4 The strictly idiographic approach which employs individual 
proﬁ les of violent offenders to detect those on a similar pathway 
to attack. The idiographic approach is employed to evaluate the risks of rare events, such as attempts to assassinate a head of state, and has little application in general mental health.
5 A plethora of local risk assessment tools have sprung up.

5 A plethora of local risk assessment tools have sprung up. 
Sometimes it seems as if every psychiatric service, probation/parole service, prison, and security consultant have their own unique sheet of questions which are supposed to establish the future probability of whatever particular piece of nastiness currently concerns the organization. These ad hoc parochial risk assessment protocols have no evidentiary basis or psychometric integrity (even if they incorporate aspects of other properly constituted instruments). It is far better to validate existing

1995
empirically supported measures for use in a particular setting 
and with a particular population.
The core of risk assessment is the systematic application of 
probability models usually incorporated in standardized instruments.
The utility of risk assessment
Even given a ﬁ  rmly based knowledge of those factors which in 
populations may increase or decrease the probability of violent behaviour, there remain theoretical and practical limitations on effective prediction in the individual case. If factors were identiﬁ  ed 
which occurred only in the violence prone and never in the paciﬁ  c

which occurred only in the violence prone and never in the paciﬁ  c 
and, if present, were in every case the harbinger of future attack, then the power of the predictive paradigm would be independent of both the frequency of future violence in the population, and of variables which effect the factors’ expression in the individual case. In the real world the sensitivity (the accuracy with which the outcome is predicted) and the speciﬁ  city (the extent to which only 
those who will act in the predicted way are identiﬁ  ed) fall short of 
100 per cent. This being so the less common the future behaviour in the population the less speciﬁ  c will become predictions. Equally, 
the more complex the inﬂ  uences affecting the expression of the 
identiﬁ  ed predisposition the less the sensitivity of the predictive 
paradigm.
Say we develop a predictive paradigm of 70 per cent sensitivity 
and 95 per cent speciﬁ  city (which is feasible). If we set an accept-

paradigm.
able level for the practical use of such an instrument that it will not unfairly restrict, or stigmatize, more than 1 person for every 4 correctly designated as candidates for future violence, then the base rate for violence in the population of interest would have to exceed 20 per cent. Even if we accepted one error for each correct designa-
tion (which, if the outcome of ascertainment were incarceration 
or other signiﬁ  cant curtailment of basic freedoms, few would 
regard as ethically defensible) it still requires a base rate of higher than 6 per cent.
This hopefully makes clear that if predictions of the probability 
of future violence are to be used to signiﬁ  cantly restrict the patient’s

of future violence are to be used to signiﬁ  cantly restrict the patient’s 
freedoms the base rate of the behaviour must be reasonably high in the group under consideration. Equally, if measures such as long term institutionalization or compulsory community treatment with restrictions on residency and movement are contemplated the degree of violence apprehended must be commensurately damaging. It would be difﬁ  cult to justify such interventions if 
what is at issue is embarrassing, or even fear inducing behaviour, which does not involve either assault occasioning injury or gross intimidation.
Statistical approaches to analysing predictive efﬁ  ciency in popu-
lations with low base rates for the target behaviour exist, the most commonly employed being derived from a measure developed for use with radar or signal detection systems, the Receiver Operating Characteristic (ROC) curve.
(24, 25) The ROC curve is a graph of

(24, 25) The ROC curve is a graph of 
true positives (sensitivity) along the y-axis and false positives (1-speciﬁ  ty) along the x-axis. With respect to violence, these corre-
spond to patients who were predicted to be violent those who were predicted not to be violent, respectively. The line running from the lower left corner of the graph to the top right indicates chance pre-diction, where true positives are equal to false positives (i.e., for every patient predicted to be a violent who in fact becomes violent 
another patient who was predicted to be violent does not become violent). A curve above this line indicates that, in this case, recidi-vism is being predicted at rates above chance. The Area Under the Curve (AUC), which is represented as a proportion of the graph that falls under the curve, reﬂ  ects the proportion of true positives

over false positive (e.g. an AUC of 70 would indicate that 70 per cent of those predicted to be violent in fact do become violent). The ROC analyses allow the accuracy of predictions to be estab-lished independent of variations in base rate.
In many western nations between 5 per cent and 10 per cent of 
all homicides and more than 5 per cent of serious crimes of vio-lence are committed by those with a schizophrenic syndrome. The annual risks of a person with a schizophrenic syndrome commit-ting a homicide is however, in the region of 1 in 10,000 and for a crime of violence about 1 in 150.
(26) This is because serious 
violence is, the media notwithstanding, an uncommon event. Though fear inducing behaviours occur with distressing frequency among the seriously mentally disordered the inﬂ  icting of serious 
injury is measured in annual risks of below 1 per cent.
(27,28,29) This

(27,28,29) This 
suggests that risk assessment instruments will not be relevant to predicting serious violence in those with a schizophrenic syndrome. Underlying the homicide enquiries in the UK, and the litigation, particularly in the US, however is the assumption that they can be and will be.
Given their particularly low base-rate of occurrence, attempting 
to predict who will commit serious acts of violence or murder will inevitably be accompanied by vast numbers of false accusations. Further, in reality we often trade off outcome variables, thus avoid-ing over ready resort to civil commitment may improve the chances of establishing a long term therapeutic alliance, which in turn may reduce long term risks, albeit at the price of tolerating a higher degree of risk in the short term. Avoiding all probability of any patient committing a future act of violence would involve the use

of widespread coercion and move mental health professionals into 
increasingly custodial and controlling roles.
An alternative argument deserves consideration. In those with a 
schizophrenic syndrome, for example, it may well be feasible to identify the 10 per cent who will perpetrate 90 per cent of all the future fear inducing and violent acts. In this 10 per cent may be included nearly all of the far smaller number who will commit potentially lethal or seriously injurious acts. In effectively identify-ing the 10 per cent and managing them appropriately then the risks to the community of damage, including the small chance of serious damage, will be reduced. The majority of those so identiﬁ  ed will be 
a nuisance who can occasion fear, and who may push, punch or kick others.
(30) Effectively identifying and managing all patients in 
the high risk group will lower the overall risk to the community while minimizing the deprivation to liberty of those in the low risk

the high risk group will lower the overall risk to the community while minimizing the deprivation to liberty of those in the low risk 
group. This risk group management approach is not perfect and 
does not increase the ability to identify a particular individual who may commit a heinous act, but it does allow effective management of those at higher risk.
The management ethically and pragmatically justiﬁ  ed, must 
retain some semblance of proportionality between the apprehended insult and the impact of the proposed preventive strategy. In practice this obliges us in most clinical situations not to resort to increased coercion, let alone preventive detention, but to focus attention on 11.14  assessing and managing the risks of violence towards others

SECTION 11  forensic psychiatry 1996
greater support and more active follow up and treatment in the 
community with a more ready resort to admission during exacer-bations of symptoms or social conﬂ  ict.
Risk assessment instruments
The last 15 years or so has been marked by a wave of enthusiastic 
advocacy speciﬁ  cally for the beneﬁ  ts of so called actuarial risk 
assessment instruments (e.g.,(31,32,33)). The advocates of actuarial 
risk assessment claim directly, or by implication, to be able to iden-tify the likelihood that speciﬁ  c individuals will progress to various 
forms of interpersonal violence. These risk assessment tools are based mainly on retrospective, though occasionally prospective, studies of speciﬁ  c populations, such as discharged patients and 
released offenders. Actuarial approaches have the advantages of:-

1 Multiple variables delineating level of risk.2 Designed to move from group data to individual attribution.3 Realized in simple objective reproducible rating scales which 
minimize individual clinician’s discretion and therefore respon-sibility.
4 Focus attention on ‘high risk’ individuals (principle of targeted 
resources).
5 Provides protection to clinicians and managers in event of 
disaster. Nobody can be blamed for the failures of ‘science’ .
Actuarial approaches are not without their problems. The results, 
for example of commonly used risk assessment instruments like the VRAG and the Static 99 change little if at all over time and with circumstances. Clearly whatever the Static 99 may indicate the risks of committing further rapes in a ﬁ  t 25 year old is unlikely to remain 
the same as he ages and acquires disabilities.
(34) Actuarial approaches

(34) Actuarial approaches 
also almost inevitably revolve around a limited number of variables which exclude uncommon though potential critical factors. Thus, for example, morbid jealousy is not sufﬁ  ciently common to emerge 
as an actuarially established risk factor despite studies on such cases indicating a very high probability of signiﬁ  cant violence. The 
structured clinical judgement approach allows the incorporation of such potential modiﬁ  ers
(22). Actuarial instruments are devel-
oped on speciﬁ  c samples constituted in particular places at partic-
ular times. This can lead to problems with generalisability and equally important idiosyncratic and false attributions. For example, in both the VRAG
(31) and the Classiﬁ  cation of Violence Risk 
(COVR)(35) the schizophrenic syndrome emerges as a protective,

(COVR)(35) the schizophrenic syndrome emerges as a protective, 
or at best a neutral, factor with regard to the risk of violence, despite being associated in many other studies with far higher rates of violence than occurs in the general population.
(26) This is because 
in the VRAG the rate in those with schizophrenia was compared to other offenders, some of whom had severe personality disorders, and as expected it was lower. In the MacArthur study, from which derives the Classiﬁ  cation of Violence Risk (COVR),
(35) substance 
abuse was treated as an independent confounder and the rates for the select few who had a schizophrenic syndrome, but were not substance abusers, were used to calculate the level of risk for schizophrenia.
The use of the term actuarial links these approaches to the well

The use of the term actuarial links these approaches to the well 
established actuarial methods familiar from the insurance industry. In the insurance industry actuaries usually generate their risk groups on the basis of samples numbered in the thousands, with the occasional in the tens of thousands. In the mental health ﬁ  elds 
the samples are usually measured in hundreds, with the occasional topping the thousand mark.(1) Actuaries in the insurance industry 
work exclusively with group based predictions. Y our car insurance will depend on such variables as the type of car you drive, your age, your gender, your prior driving record, and where you live. That determines the group you fall into for the purposes of costing the policy you request. The actuary is not interested in what happens to each individual only whether the whole group for whom policies have been drawn costs sufﬁ  ciently less in claims than is received in

policy payments to produce the required proﬁ  t margin. The actu-
arial method is not designed to assign levels of risk to individuals but to groups, though the cost of an individual’s policy will be determined by the risk group into which their policy falls. The precision of the group prediction is determined by the size of the sample and the frequency with which the event of concern occurs. The rarer the outcome of interest (e.g., murder or plane crashes) the larger has to be the sample, and to some extent the commoner the event (minor assaults or fender benders) the smaller the sample. Irrespective of the sample on which the risks have been established as you try to make ﬁ  ner and ﬁ  ner distinctions involving 
smaller and smaller subdivisions within the original sample so the conﬁ  dence that can be placed in the estimate decreases. Paradoxically

smaller and smaller subdivisions within the original sample so the conﬁ  dence that can be placed in the estimate decreases. Paradoxically 
the more intense and detailed the analysis of the original group the less reliably can the derived risk algorithm be applied to those outside the group.
(19)The MacArthur study on which the COVR 
is based exempliﬁ  es this problem. The smallest unit is obviously the 
individual group member and here the inherent variability of the risk prediction will be at its highest.
T o take the example of two of the most widely used and best 
established actuarial risk instruments. The VRAG claims to identify nine groups, known by the unfortunate term ‘bins’ , with a prob-ability of future violent recidivism varying from 0 per cent to 100 per cent.
(31, 32) The analysis of Hart and colleagues(36) demon-

strates that rather than nine statistically separable groups there are only three statistically distinct groups. The Static 99 claims to separate sex offenders into 7 groups with recidivism rates varying from less than 10 per cent to greater than 50 per cent.
(37) Statistically 
however only two separable groups are generated one with offend-ing rates between 4 per cent and 25 per cent and one between 30 per cent and 60 per cent.
(36) In short even ignoring the all important 
problem of attributing a group risk to an individual within the grouping the Static 99 identiﬁ  es recidivism with at best 2 in 3, 
and at worst 1 in 3, chance of accuracy. In this really good enough to damn a person to indefinite incarceration or extended imprisonment?
Unfortunately, unlike other areas that rely on actuarial approaches

Unfortunately, unlike other areas that rely on actuarial approaches 
to decision-making, there has not been a concerted effort in the area of violence risk assessment to pool the results of various studies to obtain the large samples necessary to reduce the variance which would thereby reduce the broad values on the conﬁ  dence intervals. 
1 There are notable exceptions, such as the Level of Supervision/Case 
Management Inventory which has accrued normative data on more than 35,000 prisons and almost 80,000 people under community corrections supervision [Andrews, D. A., Bonta, J. L., & Wormith, J. S. (2005). Level of Service/Case Management Inventory (LS/CMI). T oronto: Multihealth Systems.].

1997
As noted in Footnote 1 above, there are some exceptions such as 
the LS/CMI. Doubtless, over time researchers will pool results to determine the extent to which conﬁ  dence intervals can decrease, 
thereby increasing the predictive utility of instruments.
The big question which hangs over the use of risk assessment 
instruments is the extent to which it is possible, or acceptable, to make attributions about an individual’s future behaviour on the basis of their sharing characteristics with those in a group with a known level of risk for such behaviour. In medicine we are so used to using probabilities to dictate our actions that there are dangers in failing to recognize the problems. An 18 year old woman pres-ents with a history of severe central abdominal pain moving to the right iliac fossa associated with anorexia. The probability in those with similar symptoms of an inﬂ  amed appendix may be 30 per

cent but 100 per cent of the patients are advised to have surgery. Probability is used here to provide advice entirely in the interest of the patient. If the advice is refused the patient is not forced into surgery but is observed and managed non-surgically. Compare this with advice to a court or tribunal considering extending the incar-ceration of an offender or patient. The offender may have similar characteristics to those with a better than 50 per cent (or even 80 per cent) chance of re-offending and to attribute the group risk to the individual may beneﬁ  t the community. It will however almost 
certainly disadvantage the individual who will not be the one accepting or rejecting the advice. It is fallacious to argue that mak-ing such attributions from group membership to individual risk is acceptable because it reduces the errors of false positives. It is not possible to beneﬁ  t the so called low risk without disadvantaging

the rest. Even with particularly strong measure of risk assessment, the false positive rates still hover around 25 per cent.
The only strong defence of attributing risk to an individual by 
virtue of their group membership, which is the essence of preju-dice, is that it has better outcomes than not using this approach. But what are better outcomes? Better outcomes could be reduced to the accounting of true and false attribution. On this basis actu-arial risk assessment instruments perform better than the best guesses of most experts. In the case of possible appendicitis given the beneﬁ  ts of early versus delayed intervention a high number of

false positives is tolerable to avoid even one false negative. When the outcome is imposing further incarceration even the price of one false positive for every true positive, which the Static 99 and VRAG might offer may raise moral and legal qualms. Particularly as given both the true and the false positive will be incapacitated making it impossible to ever know which was which. There is no quick corrective feedback in the world of assessing the risk of future criminality, unlike appendicitis where the pathologist will soon tell you if you were right or wrong. Further when supposedly low risk individuals are discharged or released and re-offend, this will rein-force any tendency to err on the side of caution and incarceration.
Statistical decision theory can support using group membership 
to attribute levels of probability to individual group members. Though even here sceptics might suggest that the efforts put into 
Bayesian approaches to make the best of limited data sets might

Bayesian approaches to make the best of limited data sets might 
better be expended in enlarging such data bases. What in any case 
the approach cannot do is decide on utility and moral propriety. It is only relatively recently that the criminal justice system has moved to making the prediction of future offending the dominant issue in determining sentences, parole, and the extensions of sentences (which in and of itself is an entirely new phenomenon). Similarly the emphasis on the risks psychiatric patients present to others is a relatively recent preoccupation for mental health 
services. The development of standardized risk assessment instru-ments not only serves these changes but sustains them. The sexual predator legislation in the US, the DSPD and indeﬁ  nite sentencing

services. The development of standardized risk assessment instru-ments not only serves these changes but sustains them. The sexual predator legislation in the US, the DSPD and indeﬁ  nite sentencing 
provisions in the UK, and the extended supervision/imprisonment laws in Australasia, are all dependent on mental health profession-als providing them a veneer of science and objectivity through risk assessments.
(38, 39) While providing the courts with information 
regarding the extent to which the individual’s characteristics place them in a general level of risk we by implication give our assent and support to that process. We place a hope for community beneﬁ  t 
before an inevitable disadvantage to those with whom we have engaged professionally.
The current state of the science of risk prediction some might

The current state of the science of risk prediction some might 
suggest delivers only a limited improvement in the decision mak-ing process. If they are correct what, if anything, remains in the risk assessment literature of practical value? The short answer is that the establishing of risk factors remains of inestimable value, not in placing labels on individuals but in identifying how to reduce the probability of future violent and criminal behaviours. The stan-dardized risk assessment approaches such as the HCR-20 and the VRAG allow individuals to be assigned to broad levels of high, low or medium probability of future violence. It can be argued whether or not the conﬁ  dence that can be placed in such attributions justify 
imposing extended incarceration. They are however of undoubted value in assigning priority for management interventions.

The structured professional judgement measures, such as the 
HCR-20, also add considerable value by identifying risk factors, such as substance abuse, speciﬁ  c personality vulnerabilities, and 
the like allowing targeted interventions to reduce the chances of engaging in violence and offending. The exposure of the current limitations in the project of identifying dangerous individuals is bad news for courts, parole boards and governments looking for short cuts to community safety. But for mental health professionals it is merely a reminder that our business is managing patients to reduce the risks for them and for others, not trying to separate the dangerous goats from the mostly harmless sheep.
The limitations on the ability to accurately predict risk also empha-

size that in all circumstances where psychiatrists and psychologists are being asked to provide opinions of risk of future violence to courts or other decision-making bodies, they should provide the courts with the information that they can. This would include, for example, the general risk level in which the risk assessment tools would place the patient but it would also extend to an anamnestic consideration of factors in the patient’s case that are known to increase or decrease the level of risk. In the end, though, the clini-cians need to be clear to state the limitations of their ﬁ  ndings and to, 
of course, leave the ultimate decision of whether the patient meets 
the criteria of the statute in question to the legal decision makers.
Practicalities of risk prediction and management
Risk assessment and management can be conceptualized as a four 
stage process:

1 An evaluation of general level of risk and priority for active 
intervention. In practice this can rarely go further than saying they are in a high, medium, or low, priority or risk category.
2 Identify current risk factors and future hazards which are both 
potentially remediable and causally relate to increased chances of violence.11.14  assessing and managing the risks of violence towards others

SECTION 11  forensic psychiatry 1998
3 Develop management strategies to reduce or remove the delete-
rious inﬂ  uence of these factors.
4 Evaluate the effectiveness of the interventions in reducing subse-
quent violence.
Each of the above steps will be discussed in turn below.
Evaluating level of risk
Such evaluations should start simple, consider the context, apply 
clinical and common sense, then potentially progress to the use of a standardized assessment instrument. In both the mentally disor-dered and general population the majority of violent and criminal behaviour is committed by young males with histories of repeated antisocial behaviour dating back to conduct disorder in childhood. This is often combined with anomie, that lawless disaffection with society in general and contempt for rules and authority in particular. Impulsiveness is concerning
(40) but so is the more muted

(40) but so is the more muted 
feckless disregard for consequences found in some with a schizo-phrenic syndrome. Unemployment, living in a high crime neigh-bourhood, and antisocial peers all add substantially to risk. Similarly substance abuse is a robust maker for the risk of criminal-ity in the disordered and non disordered alike. Speciﬁ  c to the 
seriously mentally disordered is a refusal to recognize they are ill, and resistance to complying with treatment with often an antago-nism to professionals; the ‘fuck off and leave me alone’ syndrome.
Clinicians must maintain their common sense. A range of situa-
tions must be taken seriously. The angry and threatening who can tell you exactly what they plan to do to their supposed antagonist, the frightened who see no alternative to a pre-emptive strike, those who have prepared for violence (weapons, surveillance, put their affairs in order), the actively suicidal who have nothing to lose

but still care enough to take a ﬁ  nal revenge, and commonest of all 
those making threats in a manner which creates fear and concern either in the potential victim or those who have been privy to the threats.
Beyond normative data and risk factors, there exist a number of 
high risk situations and syndromes particular to psychiatry. These include:-
1 Morbid jealousy
2 Some misidentiﬁ  cation syndromes
3 Depressed suicidal mothers of young children.4 Delusional systems focussing on speciﬁ  c individuals believed 
to present for the patient a serious threat, or a malevolent imped-iment to their central project.
5 Some stalking situations6 Confusional states be they toxic or related to dementia or other 
cerebral impairments (this is the source of a signiﬁ  cant propor-
tion of assaults on health staff)
Patients presenting any of the above characteristics require 
careful assessment and management to reduce the likelihood that risk will eventuate.

When there is an indication that a patient may be at an elevated 
level of risk for violence, or when the clinician is doing a risk assess-ment speciﬁ  cally, there is much to be said for becoming familiar 
with the use of standardized risk assessment instruments. They can direct attention to important areas that require consideration and provide a structure for both gathering and evaluating relevant 
information. The choice is between the actuarial (e.g., VRAG, Static 99 and COVR) and those employing structured professional judge-ment (e.g., HCR 20). The former generate ﬁ  xed risk levels, the 
latter in their nature are open to further modiﬁ  cation in the light of

latter in their nature are open to further modiﬁ  cation in the light of 
clinical and common sense. Pure actuarial instruments (e.g. Static 99 and COVR) may appeal to the less experienced given their relative simplicity of administration. Their disadvantage even for the expert is, however, that they can function like black boxes which generate evaluations without the user being necessarily aware of 
how the instrument was constituted and the limitations that should 
attend its use. Moreover, they have been validated for use in fairly limited contexts and countries. As a result, clinicians may put undue weight on the results the instruments produce, without knowing how the results might vary in the context in which they are working.
Structured professional judgement is more transparent, if more

Structured professional judgement is more transparent, if more 
demanding of the user. Where the actuarial measures can be used by relatively poorly trained individuals or in some contexts clerical staff, the structured professional judgment measures must be employed by those with considerable expertize. We favour the structured professional judgement approach of the HCR 20 but readers need to understand that actuarial instruments are perhaps the dominant forms of risk assessment instrumentation, due in no small part to their reliance on static variables and ease of administration. The HCR 20 is designed for use with general and forensic psychiatric patients and it has been found to have utility in general offender populations. Those whose work brings them into contact with speciﬁ  c groups such as perpetrators of domestic 
violence, child molesters or stalkers should consider using risk assessment approaches developed speciﬁ  cally for these populations

violence, child molesters or stalkers should consider using risk assessment approaches developed speciﬁ  cally for these populations 
(e.g., the Spousal Assault Risk Assessment (SARA),
(41,42)  Sexual 
Violence Risk-20 (SVR-20),(43) Risk for Sexual Violence Protocol 
(RSVP).(44, 45)
The end point of a risk analysis in most cases will allow individu-
als to be placed into one of three somewhat arbitrary groups which encompass both likelihood and potential level of damage:-
 i)   High Risk – the individual presents a signiﬁ  cant risk of com-

i)   High Risk – the individual presents a signiﬁ  cant risk of com-
mitting a seriously damaging act of violence within a reason-able timeframe (less than a year or so). It is generally impossi-ble to quantify the numerical probability for ‘high risk’ as it will vary across instruments and in different situations from approximately 30 per cent (sexual offending) to 80 per cent (the occurrence of general violence). Management of the risk is required immediately and the level of risk should be re-evalu-ated periodically depending on the extent to which the individ-ual’s personal situation and dynamic risk factors may vary. When the potential violence is of a particularly horrendous nature (e.g. potentially lethal) the timeframe can reasonably be extended to encompass a number of years. In, for example, some predatory child molesters and some who have killed from morbid jealousy, the chances of re-offending may be substan-tial and continue virtually throughout the offender’s life span.

ii)   Moderate Risk – the individual presents a real risk of commit-
ting a damaging act which might inﬂ  ict minor injuries and/or 
signiﬁ  cant fear and distress within a year or so. This group 
also requires their level of risk to be managed though, because the severity of behaviour is less extreme and the time period

1999
perhaps less imminent, the extent of management is less inten-
sive or restrictive. Also in this group can be placed those with a more remote (less than 30 per cent) but not inconsequential (above 5 per cent which in practice is the limit of reliable detec-tion) risk of serious violence. Examples include those at lower risk of committing acts of a more serious nature (e.g., those making viable and tangible threats of engaging in behaviour which would lead to harm).
iii)  Low R isk – Individuals who do not present a real risk of 
harming a third party. Their level of risk and potential for severe risk is low. They do not require any risk management plan beyond normal care and there is no need to re-evaluate the risk at any time in the reasonably foreseeable future. In essence, this category includes everyone not in the High or Moderate categories.
A ﬁ nal re-emphasis. Even using standardized instruments the 
ﬁ nal evaluation has to take into account factors beyond the ﬁ  gures

ﬁ nal evaluation has to take into account factors beyond the ﬁ  gures 
generated by the black box. Risk evaluation is about formulation not simply calculations.
Identifying factors relevant to 
decreasing risk
The primarily clinical purpose of risk assessment should be risk 
management. Risk management is about identifying those factors which mediate the increased risk and modifying them to decrease risk. The structured professional judgment instruments and a good working knowledge of the risk literature will assist the clinician to identify and understand relevant risk factors. As noted above, identiﬁ  cation of the dynamic risk factors points directed to poten-
tial management approaches. A simpliﬁ  ed schema of the mediators

tial management approaches. A simpliﬁ  ed schema of the mediators 
and moderators which link having a schizophrenic syndrome to violent behaviour is presented in Fig. 11.14.1 with the basic approach to breaking or attenuating those links represented in Fig. 11.14.2.The management strategies in high risk groups take us directly to 
good clinical practice with the addition of few speciﬁ  c approaches. 
The basic approach to management of high risk individuals can be summarized:
1 Substance abuse. This claims ﬁ  rst place not because it is neces-
sarily the most important risk factor but because the presence of the signiﬁ  cant abuse of alcohol or drugs can disrupt all other 
management approaches.
2 Psychopathology. Obtaining adequate control of the delusions,

2 Psychopathology. Obtaining adequate control of the delusions, 
affective disturbances, and hallucinations which predispose in some cases to offending behaviours is the second management imperative. Again without adequate control of the psychopathol-ogy little progress is likely in more targeted treatment modalities. High risk groups are often reluctant to comply either with medi-
cation or psychological management. This may force the use of 
compulsory treatment in an inpatient situation for sufﬁ  cient time 
for the patient to begin to experience the beneﬁ  ts of ameliora-

tion of their active psychosis. Extended admissions (4–12 weeks) also provide an opportunity to establish trusting therapeutic relationships, though equally they can be productive of resent-ment and even more marked resistance to treatment. Second generation antipsychotics are preferable in this group as they are better tolerated and less likely to further impair cognitive and particularly frontal deficits. Depot medication is useful initially though this currently restricts considerably the choice of medication at least until more second generation antipsychotics come available in depot format. Clozapine can be particularly effective in this group but the level of cooperation required usually prevents its use at least in the early phase of management.

3 Social Circumstances. Discharging high risk patients to disorga-
nized or casual accommodation in high crime neighbourhoods virtually guarantees offending behaviours. Similarly the drift back into contact with substance abusing peer groups increases risk and further disrupts management. Unemployment or just 11.14  assessing and managing the risks of violence towards others
Developmental Difficulties Active Symptoms
Personality Vulnerabilities
Education Failure
Unemployment Social Dislocation Substance Abuse
Criminal Peer Group
Rejection by
Service
Violent Behaviours
Fig. 11.14.1 A simpliﬁ  ed schema of the mediators and moderatory between 
having a schizophrenic syndrome and behaving violently are illustrated. The very complexity of the nexus between illness and violence offers multiple opportunities for intervening to break the links. [Reproduced from Mullen, P .E., 
(2006). Schizophrenia and violence: from correlations to preventative strategies.

(2006). Schizophrenia and violence: from correlations to preventative strategies. 
Advances in Psychiatric Treatment , 12, 239–48, copyright 2006, The Royal College 
of Psychiatrists.]Breaking the Links to Violent Behaviour
Early Intervention Vigorous Management of
Active Illness
CBT for Personality
VulnerabilitiesManage
Substance Abuse 
Education Enhancement Compulsory I.P.
Management if indicated 
Social Skills Training
Placement in Supported
Accommodation in low
crime neighbourhoodsWorks Skills Training
Fig. 11.14.2 Illustrates some of the interventions which could reduce the 
strength of the association between having schizophrenia and behaving violently. All interventions depend on accepting that it is the services duty to manage both the violence which can emerge from schizophrenia, and those with schizophrenia who are also substance abusing, delinquent and objecting. [Reproduced from

Mullen, P .E., (2006). Schizophrenia and violence: from correlations to preventative 
strategies. Advances in Psychiatric Treatment , 12, 239–48, copyright 2006, The 
Royal College of Psychiatrists.]

SECTION 11  forensic psychiatry 2000
the lack of structure to their days increases risk. An absence of 
non offending, non substance use satisfactions leaves patients vulnerable to offending. The high risk groups need stable accom-modation in low crime neighbourhoods, with active support, and structured recreation with later more long term educational and work related activities. Assisting them into contact with non deviant social groups (via sport, voluntary work, employment, or hobbies) is essential to establish social rewards to replace the pleasures of substance use and crime.
4 Insight. Or more concretely the acceptance of the need to change 
their attitudes and behaviours which support criminal and vio-lent behaviours is a requirement for more targeted interventions. The stages of change model
(46) combined with motivational 
interviewing(47) can assist in beginning the process. Ultimately it

interviewing(47) can assist in beginning the process. Ultimately it 
is through establishing a trusting relationship with the therapist and ideally the treatment team that commitment to change and maintaining change is obtained.
(48)
5 Personality Traits. Personality disorders may or may not respond 
to treatment but the traits out of which they have been con-structed are mostly open to modiﬁ  cation. The objective is not to 
transform a suspicious, manipulative, insensitive, self absorbed thug into a paragon of the social virtues. It is simply to amelio-rate those traits which predispose to antisocial behaviour. Targeted CBT offers a range of options. Wong and Hare’s
(49)
guide to managing psychopathic traits offers a useful source of guidance for developing such programs.
6 Victim Empathy. Assisting the high risk group to understand the

(49)
6 Victim Empathy. Assisting the high risk group to understand the 
impact of their behaviour is essential. Sadly this is often best approached through sensitizing them to the harm they bring on themselves rather than through victim empathy programs, but both are worth attempting.
7 Common Sense and Prudential Wisdom. High risk patients with 
a schizophrenic syndrome not infrequently lack the mundane capacity to foresee the obvious outcomes of their behaviour. This produces a feckless foolishness. Instilling prudential wisdom in those impaired in this manner is a matter of slow progress in structured interactions which focus on their actual behaviours and the enhancement of the capacity to modify those behaviours in function of their longer term outcomes.
There are signiﬁ  cant pressures and obligations—both legal and

There are signiﬁ  cant pressures and obligations—both legal and 
professional—for mental health professionals to give prominence to risk assessment and management with their patients (clients). The extent to which risk assessment will be more or less prominent will depend largely upon the nature of the professionals work, and the environment in which it occurs. Caring for those with high prevalence disorders in private practice will have little to worry about. For those responsible for patients who are acutely psychotic and of course those working in forensic contexts, the importance of risk assessment will be more signiﬁ  cant.
We are at an important crossroads in our level of knowledge 
about both violence among psychiatric patients and about risk assessment. The fact that the risk for violence among psychiatric patients is not insigniﬁ  cant does mean that risk assessment and man-
agement is a legitimate activity for mental health professionals.
(45)

(45)
As such, psychiatrists and psychologists must become familiar with the risk assessment literature and emerging technologies. With 
appropriate levels of knowledge and training, clinicians can master this complex area in a way that can serve to satisfy their profes-sional and legal obligations. Only with a good understanding of the ﬁ  eld can we be protected from the risk of either blithely neg-
lecting the violence risk our patients pose or of becoming so risk averse so as to unnecessarily and arbitrarily restrict our patients’ liberty.
In the area of risk assessment, the framing of the main research

questions and the articulation of the resulting data is increasingly in terms of actuarial risks and the generation of standardized ques-tionnaires which will generate predictive scores. The technology of risk assessments could become one of the primary mediators of the relationship between the professional and the mentally disordered person. This will radically alter how the patient and their disorders and disabilities are revealed to us. We must not allow the techno-logical focus on risk to replace the importance of the patient’s per-sonal and social context. We must not allow it to objectify them and their disorder as an embodiment of a quantum of ‘riskiness.’ T o this end, there is an argument to occasionally separate the formal risk assessment task from that of patient treatment. The roles are blended—as they should be—in most cases, such as car-ing for voluntary patients and those involuntarily committed for brief periods. When the question of the patient’s level of risk is that

roles are blended—as they should be—in most cases, such as car-ing for voluntary patients and those involuntarily committed for brief periods. When the question of the patient’s level of risk is that which will determine their liberty over the long term, however, it is less tenable for a treating clinician to maintain a productive thera-peutic relationship with patients while holding the reins on their

liberty (e.g., consideration of reviews of indeterminate dispositions, 
evaluations of risk for sentencing purposes and parole decision-making).
T echnology is about performance and control, it is about domi-
nation, and the objects of technological manipulation are just that, objects [see
(50, 51)]. T o the extent that technological approaches to 
risk assessment come to dominate clinical practice, whatever ben-eﬁ t they may bring, the price will be reframing the clinician’s view

risk assessment come to dominate clinical practice, whatever ben-eﬁ t they may bring, the price will be reframing the clinician’s view 
of their patients as potentially dangerous things. Risk assessment forms part of a major shift in psychiatric practice and theory away from individually based engagements between clinicians and uniquely troubled individuals to a world of standardized best practice. Instruments direct diagnosis, diagnosis determines which system of treatment is to be applied and risk assessments enable us to prevent damage to, or by, the objects of our professional respon-sibilities. Efficient, effective, properly evaluated performances of mandated procedures becomes the deﬁ  nition not only of the 
normative but the ethical.
This chapter began with a quotation from a nobel prize winner, 
it will end with the story of another. In reading the account pro-

vided by Nasser of the schizophrenic illness of the Nobel Laureate John Nash images emerge of the complex interactions between illness and the sufferer’s humanity, life and even genius.
(52) Nash 
had a devastating mental illness, he was as a result of his illness compulsorily treated and even at times regarded as dangerous. Nash ﬁ  nally entered a stable remission in which he could once 
more work as a mathematician. This was without the continuing aid of medication or any other form of mental health ministrations. What has this to do with risk assessment and management? Everything. The outcome of an illness such as one of the schizophre-nias in an individual case remains enormously difﬁ  cult to predict. 
We must, as mental health professionals, act on our estimates of

2001
future probabilities. We should struggle to make our risk assess-
ments and risk management strategies as effective as possible. But in the end we should remain modest about our capacities to perform such predictive and preventive functions and not loose curiosity about what really delivers Nash and many others from insanity and even dangerousness.
Maden, A. (2007). Treating Violence: A guide to risk management in mental 
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Douglas, K., and Skeem, J. (2005). Violence risk assessment: Getting 
speciﬁ  c about being dynamic. Psychology, Public Policy and Law ,11,
347–83.
Ogloff, J. R. P . (2006). The Psychopathy/Antisocial Personality Disorder 
Conundrum. Australian and New Zealand Journal of Psychiatry, 40,
519–28.

347–83.
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Risk Assessment Guide (SARA) guide: Reliability and validity in adult male offenders. Law and Human Behaviour, 24 (1) , 101–18.11.14  assessing and managing the risks of violence towards others

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20: Professional guidelines for assessing risk of sexual violence. British 
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the modiﬁ  cation of problem behaviours. Progress in Behavioural

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52. Nasser, A. (1998). A Beautiful Mind . New Y ork: Simon and Schuster

11.15
The expert witness in the 
Criminal Court: assessment, reports, and testimony
As an expert witness in the Criminal Court, the psychiatrist ceases 
to be simply a doctor as a psychiatrist’s report and testimony addresses issues on the boundary between law and psychiatry. The 
law is not primarily concerned with the welfare of the defendant. Criminal law is concerned with justice, fact ﬁ  nding, and the attri-
bution of guilt whilst psychiatry concerns itself with the welfare of the individual, their mental disorder, and its treatment. This chapter will explore the legal framework for expert reports and testimony, standards for such work, the particular ethical dilemmas of this work and provide practical guidance on preparation of reports and testimony.
This chapter draws upon previously published work by the 
author.
(1,2) Expert evidence cannot be understood except in reference

author.
(1,2) Expert evidence cannot be understood except in reference 
to a particular legal jurisdiction. For this chapter the legal system in the United Kingdom is chosen but the general principles will apply to all jurisdictions. Issues speciﬁ  c to Civil and Family courts 
will not be discussed.
The psychiatric expert witness(3–5)
Witnesses in court can only give evidence of facts they personally perceived and not evidence of their opinion. It is for the court to draw inferences from the testimony of witnesses. The opinion of an expert witness is an exclusion to this general rule because courts need the assistance of experts to consider issues beyond their knowledge.
Lawton L.J in R v Turner established a ‘common knowledge’ rule 
governing expert evidence as follows:
An expert opinion is admissible to furnish the Courts with scientiﬁ  c

An expert opinion is admissible to furnish the Courts with scientiﬁ  c 
information which is likely to be outside the experience and knowl-edge of a Judge or a jury. If on the proven fact, a Judge or jury can form their own conclusions without help, then the opinion of an expert is unnecessary. In such a case if it given dressed up in scientiﬁ  c 
jargon it may make judgement more difﬁ  cult. The facts that an expert 
witness has impressive scientiﬁ  c qualiﬁ  cations does not by that fact 
alone make his opinion on matters of human nature and behaviour within the limits of normality any more helpful than that of the jurors themselves; but there is a danger that they may think it does … jurors do not need psychiatrists to tell them how ordinary folk who are not suffering from any mental illness are likely to react to the stresses and 
strains of life
.

.
This seems to limit psychiatric evidence to recognized mental 
disorder. However, expert advice is allowed which is ‘outside the experience and knowledge of a Judge or jury’ . The abnormal/normal dichotomy is not a rule of law but guidance. Courts have allowed evidence on a variety of conditions which would not normally be thought of as established mental disorder, for example ‘Battered Women’s syndrome’ .
Particular problems arise for the Court in respect of borderline 
conditions falling short of recognized mental disorder. Here admissi-bility will usually be determined by the court’s judgement as to whether the expert evidence addresses matters outside the experience or knowledge of a Judge or jury. Generally courts seek to limit evi-dence to established abnormal conditions.
(3,5) Courts have problems

(3,5) Courts have problems 
with evidence that utilizes leading edge or novel theory or diagnosis. The Court will require evidence that the novel theory or diagnosis is sufﬁ ciently organized or recognized to be accepted as a reliable body 
of knowledge by the profession. The expert will need to demon-strate that acceptance through reference to scientiﬁ  c literature.
(3, 5)
For medical experts, the Courts are able to establish expertise 
by reference to qualiﬁ  cation and training. Nevertheless, the expert 
must be able to demonstrate that they have the requisite expertise in a particular case. For example, a psychiatrist trained in general adult psychiatry may not be an expert in a case concerning a person with moderate to severe learning disability.
Immunity from suit
Lawyers and experts enjoy immunity from suit (civil litigation) for their professional work in court.
(3) For medical expert witnesses

(3) For medical expert witnesses 
this includes their report and any oral evidence presented in court. That immunity does not extend to immunity from report to the doctor’s regulatory body. It does not extend to subsequent actions such as duty of conﬁ  dentiality in respect of disclosure of reports to 
third parties. The judgement in the case of GMC v Meadows lays out the legal and public policy arguments for immunity from suit but with regulation by their professional regulatory body.

SECTION 11  forensic psychiatry 2004
Reliability of expert testimony
Courts need to assure themselves that an expert witness’s evidence 
is reliable. This creates an obvious problem as the very reason an expert is giving evidence is that they have expertise which the judge or jury does not possess.
Courts have utilized three broad approaches to this problem. 
The ﬁ  rst is to examine the scientiﬁ  c validity of evidence. The sec-
ond is to devise standards for expert evidence and the third is to regulate experts through formal accreditation systems.
Scrutiny of scientiﬁ  c evidence
The landmark case is that of Daubert v Merrell Dow Pharmaceuticals

The landmark case is that of Daubert v Merrell Dow Pharmaceuticals 
in the United States courts. That ruling established stringent criteria to judge reliability to include that the technique, body of knowledge, or theory can be tested, has been subjected to peer review and publication, has a known rate of error, is subject to maintenance of standards and controls and is generally accepted by the scientiﬁ  c community. This judgement is problematic for a 
number of reasons,
(6) not least because the court does not have 
that expert’s speciﬁ  c knowledge but nevertheless has to make a 
scientiﬁ  c judgement on the reliability of that expert’s evidence.

scientiﬁ  c judgement on the reliability of that expert’s evidence. 
Judgements are unlikely to be value free determinations and there is a risk that the admissibility of evidence could be distorted by policy considerations or interfere with the use of leading edge sci-ence in the court. These considerations have made United Kingdom courts reluctant to introduce a ‘Daubert’ type test but there is pressure to do so
(4,7) with public concern about miscarriages of 
justice linked to expert evidence.
Regulatory rules for expert witnesses
Courts have deﬁ  ned the standards expected of an expert witness; 
the landmark case being the judgement of Cresswell J in The Ikarian Reefer. Court judgements have been used to draw up for-mal rules governing civil family and criminal courts; for UK Criminal courts, the relevant rules are contained in Part 33, Criminal Procedure Rules.

(8) The common features are listed in 
Box 11.15.1 below. The understandable anxiety of the court to ensure experts adhere to these stringent standards may have the unfortunate effect of deterring psychiatrists from providing occasional expert reports for criminal courts.
Accreditation
In the United Kingdom, there are a number of organizations to accredit expert witnesses utilizing some combination of direct scrutiny of reports and references from legal teams. None so far have addressed the speciﬁ  c needs of the expert psychiatrist in court. 
They provide the court with some measure of an expert witness’s expertise in legal matters over and above what comes from their basic professional qualiﬁ  cation. Critics have pointed out
(10) that

(10) that 
once registered accreditation is unlikely to pick up poor practice, as experts with years of experience, but not necessarily competence, are unlikely to be refused accreditation. Accreditation is unlikely to prevent expert straying outside their area of expertise. These schemes have not as yet been able to deal effectively with problems of accrediting inexperienced but competent aspiring expert wit-nesses. T o be effective they may require codes of discipline with the attendant danger of attracting vexatious complaints. The Royal 
College of Psychiatrists in the United Kingdom utilizes a compe-tency based training framework together with standards for con-tinuing professional development (CPD) following training to 
promote a high standard in medico-legal work. Evidence of com-

pletion of such training and CPD is likely to be the most effective way of demonstrating credibility as an expert witness.
Ethics
Dual role
Stone(11) used the term ‘dual role’ to describe the psychiatrist in the 
legal context. In Stone’s view the role of the clinician and medical examiner for Court are irreconcilable. The evaluee/patient is unable to distinguish the role of the medical examiner as a Court expert from that of personal physician. This result is an inability to protect Box 11.15.1  Common features of regulatory rules for civil family 
and criminal courts.
Expert Reports should contain:
 1 Details of academic and professional qualiﬁ  cations together 
with experience and accreditation relevant to the opinions expressed in the report (usually as a summary in the intro-duction with more detail within and Appendix).
 2 A statement of the range and extent of expertise together

2 A statement of the range and extent of expertise together 
with limitations upon that expertise, particularly declaring when a particular issue is outside his expertise.
 3 A statement setting out the substance of all instructions 
received together with listing all materials provided and considered, upon which the opinion is based.
 4 Where there is a range of opinion on matters dealt with in 
the report, a summary range of opinion together with rea-
sons for the experts preferred opinion (see section below on Report Writing).
 5 A declaration of any facts, materials, or investigations which 
might bear upon or be made against the expert opinion.
 6 Extracts of literature or any other material upon which the 
scientiﬁ  c evidence is based.
 7 A statement of which facts are within the expert’s own 
knowledge and which are assumed.**
 8 Where an opinion is qualiﬁ  ed, a statement to that effect.
 9 A statement that the expert has complied with his or her

 9 A statement that the expert has complied with his or her 
duty to the court to provide independent assistance by way of objective unbiased opinion in matters within his or her expertise.
10 A statement that the expert will inform all parties, including 
the court, in the event that his or her opinion changes on any material issue.
11 A declaration of truth.
** Courts distinguish true and assumed facts. The only facts the 
psychiatric expert will routinely know to be true are the results of examination and results of tests or investigations. All other facts will be assumed to be true.
(9)

2005
themselves from inadvertent disclosure that might adversely affect 
the outcome in Court. He argued that clinicians cannot help using their therapeutic skills to engage the patient in disclosure. The dual role arises from the use made of the resulting psychiatric evidence for non-welfare purposes. Appelbaum
(12) argued that the dual role 
of psychiatric experts in Court is best managed by understanding that psychiatrists operate outside the medical framework when they undertake forensic Court work and their practice is not governed by the ethical principles underpinning medical practice (beneﬁ  cence and non-maleﬁ  cence). Instead he argued that psychi-
atric experts should operate from a perspective of justice ethics employing ethical principles of objective truth ﬁ  nding and respect 
for the person (termed autonomy and truthfulness).
If this solution to the Dual Role dilemma were accepted, it would

If this solution to the Dual Role dilemma were accepted, it would 
mean that the psychiatrist should not have a welfare/treatment role in respect of the person under evaluation. In the United Kingdom this is untenable
(13) primarily because of Mental Health law which 
provides for diversion to the health system as a sentence following a ﬁ nding of guilt (Hospital order). Weinstock et al.
(14) have argued 
in the United States legal and clinical context the Appelbaum solu-tion
(12) is, untenable in that legal context as psychiatrists routinely 
have conﬂ  icting responsibilities thrust upon them where legal or 
other requirements may take precedence over patient welfare.
Reports addressing sentencing in the United Kingdom place the 
psychiatrist in a Dual Role position. This is because the psychiatric opinion can result in two outcomes for the evaluee

1 A welfare disposal under Mental Health legislation.2 Potentially greater restrictions on the defendant, including 
an indeterminate life sentence where there is expert evidence on mental disorder but no recommendation for a welfare disposal.
Statutes that introduce indeterminate life sentences for public 
protection based upon assessed future risk of re-offending cause particular problems.
(1,13,15) English Courts have, through case law 
and practice, sought psychiatric evidence when they consider defendants may have mental disorder and where the Court is con-sidering an indeterminate life sentence.
(1) Psychiatric evidence on

(1) Psychiatric evidence on 
risk will be central to the expert’s evidence. The Court may have two options, a Hospital Order in suitable cases or an indeterminate life sentence. The psychiatrists does not have ‘a priori’ advance knowledge of what the outcome might be in a particular case thus routinely placing the psychiatrist into a dual role in respect of the evaluation.
Calvedeno
(16) has pointed out that even where a welfare disposal 
is recommended, medical evidence in respect of special restrictions to a Hospital Order may lead to lengthy periods in hospital justiﬁ  ed 
not by the need for treatment but by psychiatric judgement on risk in the future. Similar arguments apply to reports to Mental Health Tribunals for patients detained under mental health legislation.

One solution to the dual role is to act only where there is a realis-
tic prospect of beneﬁ  t to the patient. This leads some psychiatrists 
to only undertake work for defence teams. In the author’s view, this is unethical as it lends itself to bias and deprives one side in the adversarial process of high quality experts.
A theory of mixed duties to address dual role conﬂ  ict
Doctors are members of society and as citizens have responsibilities, 
prior to responsibilities as a doctor. The narrow domain of medical ethics does not remove from doctors their duty to consider the 
interests and rights of other people and to consider the distribution of beneﬁ  ts and risks. Beauchamp
(17) proposes augmenting tradi-

tional medical ethics with principles he terms justice and respect for autonomy. On that basis O’Grady
(1) suggests a framework of 
mixed duties for expert witnesses in court to address their ‘dual role’ conﬂ  ict (see Box 11.15.2).
This approach implicitly requires the psychiatrist to work within 
a framework of conﬂ  icting duties where ethical judgements must 
balance the welfare of the evaluee against the rights of others and society’s legitimate interest in protection from risk.
The psychiatric ethical expert in court is then the one who 
‘feels the tension’ inherent in a dual role and is painfully aware of the conﬂ  icting demands of different ethical imperatives.
Sentencing where public protection is a central issue poses

Sentencing where public protection is a central issue poses 
particular difficulties for the psychiatrist as risk assessment becomes central to the court’s decisions. Actuarial risk assessments can be particularly dangerous in the legal context. Mullen
(18) argues 
‘The margins of error in every actual or conceivable risk assessment instrument are so wide at the individual level that their use in sentencing, or any form of detention, is unethical’ . Whilst acknowledging the signiﬁ  cant limitations of risk prediction

at the individual level, the Court may nevertheless legitimately argue that evaluation of risk associated with mental disorder is an area falling outside the ‘common knowledge’ of Judge and Jury. Therefore the court must rely upon psychiatrist’s opinion on risk and mental disorder as the psychiatrist is the only witness with the necessary expertise. Using a structured risk assessment methodology may go someway to ensure accuracy, objectivity, and truthfulness. A clear role for the psychiatric expert is to ensure the Court is provided with informed scientiﬁ  c evidence on the 
limitations of risk assessment and particularly the limitations of 
utilizing structured or actuarial risk instrument at the individual level
(18,19)).
Receiving instructions
The psychiatrist should understand the legal question to be addressed; where necessary standard text should be consulted (see 11.15  the expert witness in the criminal court: assessment, reports, and testimony

Box 11.15.2  Ethical principles to address Dual Role responsibilities
1 Medical ethics:
◆ Non-maleﬁ  cence
◆ Beneﬁ  cence
2 Justice ethics:
◆ Truthfulness (objective and subjective)
◆ Respect for autonomy
◆ Respect for the human rights of others (balancing the 
distribution of benefits and risks for the patient and society)

SECTION 11  forensic psychiatry 2006
recommended reading). The psychiatrist must ensure that they 
have the necessary expertise to address the issues for the Court. Trainees must ensure that they are supervised by a suitably quali-ﬁ ed senior and disclose this to the instructing party (including 
disclosure of the supervisor’s appointment and qualiﬁ  cations).
The psychiatric expert must ensure that they can meet the needs 
of the Court as regards timescale for the report and understand that they can be compelled by the Court to give oral evidence; for example when they are on leave. The Court will not do so if the doctor has in advance disclosed dates when they are unavailable. Where there are fees to be paid, the letter of acceptance should state the contractual conditions for accepting instructions.
Rules of evidence in all legislations impose on the expert witness

Rules of evidence in all legislations impose on the expert witness 
an overriding duty to the court outside of the duty owed to the party instructing them. The psychiatric expert witness has to develop a working relationship with the legal team instructing them but simultaneously discharge their overall duty to the court. One way of conceptualizing the relationship to the instructing party is as a ‘consultant’ to the legal team, educating them in the meaning of psychiatric ﬁ  ndings.
(20) Nevertheless it is naive to 
believe that expert will not be subject to overt or subtle inﬂ  uence 
by the instructing side.
Psychiatric reports should comply with relevant court rules for 
example Part 33 of the Criminal procedure rules for England.(8)
Notes and documents must be retained for a sufﬁ  cient period 
(undeﬁ  ned but at least to until last date for appeal) and disclosed to 
other experts in the case.(20) The expert should have appropriate 
indemnity insurance.
The interview

If the defendant is to be visited in prison, arrangements should be made well in advance and comply with the requirements of the institution.
At the beginning of the interview, the examining psychiatrist 
should explain carefully to the defendant the nature of the doctor’s dual role, the limits of conﬁ  dentiality in producing a medico-legal 
report and that the Court will have full disclosure of all material known to the report writer (no off record material). It is prudent to obtain a signed record of this discussion and to include it as part of the introduction to the report. Whenever possible, an informant should be interviewed; by telephone if necessary.
Structure of the report
(a) Declarations and introduction
The ﬁ  rst section of the report should lay out the instructions

The ﬁ  rst section of the report should lay out the instructions 
received and what was done in order to produce the report. The dates and duration of interviews should be stated, including inter-views with informants. For British Criminal Courts, Part 33 of the Criminal Procedure Rules
(8) requires certain declarations and 
statements at the beginning of the report (see Box 11.7.1 above). A section on limitations to the report should be included to record matters such as documents not disclosed or unavailability of informants and state the impact on the expert’s opinion.
(b) The facts
The middle section of the report should record brieﬂ  y the facts 
upon which the opinion is based and should avoid interpretation which is the proper function of the opinion section. In psychiatric reports, the only facts that are within the psychiatrists own knowledge are likely to be those based on the ﬁ  ndings of mental state exami-

nation. All other facts are assumed. If structured tests are utilized, they may also constitute facts within the psychiatrists own knowledge.
(c) Opinion
The role of the psychiatric expert is to provide an opinion on mental disorder and its implications for the matters before the Court. The opinion section should then start with a description of the defendant’s mental disorder. If there is no evidence of mental disorder, then the privileged exception accorded to psychiatric experts no longer applies (see earlier section). The features that lead to a diagnosis of mental disorder should be described, avoid-ing jargon, and including mental state ﬁ  ndings, so that others can 
understand how the opinion is reached. The diagnosis should be clearly stated using a recognized classiﬁ  cation which for British 
psychiatrists will be the International Classiﬁ  cation of Mental and

psychiatrists will be the International Classiﬁ  cation of Mental and 
Behavioural Disorders. Where a condition is described which is not part of such recognized classiﬁ  cation systems or where ‘leading 
edge’ scientiﬁ  c ﬁ ndings are used to support the opinion that should 
be justiﬁ  ed by disclosure (as an appendix to the report) of relevant 
literature to support the expert’s opinion.
The second stage of the opinion is to translate the psychiatric 
ﬁ ndings into the legal language employed by the Courts. T erms 
such as ‘diminished responsibility’ , ‘insanity’ , or ‘automatism’ have precise legal deﬁ  nitions and the report should address how the 
psychiatric ﬁ  ndings translate to the legal deﬁ  nitions employed by 
the Court.
Usually there will be a range of opinion and the psychiatrist

the Court.
Usually there will be a range of opinion and the psychiatrist 
should indicate the range, giving due weight to alternative opinion before recording the reasons for their own opinion. More than one legal issue may have to be considered together with the range of opinion on each separate legal issue. One helpful mental model is to consider the range of opinion that might be given by other experts if the case were presented to a psychiatric case conference.
(20)
At point of sentencing where the court has concerns about 
public safety, the psychiatrist will be expected to provide an opinion on risk linked to the defendant’s mental disorder. The eth-ical issues arising from that expectation should be thoroughly understood (see section above). It is usual to express a range of opinion (the case conference model) and given reasons for the expert’s own opinion.

Where recommendations for a disposal under speciﬁ  c Acts are 
included, the precise wording of the relevant section of those Acts should be employed.
(i) Opinion on the ultimate issue
There is a common law injunction against a witness expressing an opinion upon the ultimate issue to be determined by the court. Many questions put to psychiatric experts test this rule to its limits. In this author’s opinion, psychiatric experts should provide the court with objective evidence upon the mental state in and around the time of an alleged offence but stop short of expressing an opinion on the ultimate issue unless speciﬁ  cally instructed to do so 
by the presiding Judge.
Medico-legal work undertaken by psychiatrists is governed by the 
same rule of conﬁ  dentiality as applied to other clinical work.

2007
Reports cannot be disclosed to a third party without the consent of 
the body commissioning the report. Psychiatric reports do not form part of a person’s NHS medical record except by the express consent of the individual or their legal representative. Defence solicitors can exercise a right not to disclose a report to Court. Failure to comply with rules of conﬁ  dentiality can lead to civil 
action or report to a professional regulatory body.
There may be circumstances where a psychiatrist believes that it 
is necessary to divulge conﬁ  dential information to a Court without 
the evaluee’s consent. This could arise:
(a) Where the evaluee refuses to cooperate with the preparation 
of a report.
or
(b) Where a report is not disclosed but the psychiatrist believes 
that disclosure is in the public interest.
A psychiatrist who believes that the evaluee is not cooperating 
with the preparation of a report because of mental illness has a

with the preparation of a report because of mental illness has a 
duty to consider whether the evaluee’s mental illness could inter-fere with a fair trial (for example, ﬁ  tness to plead or lack of consid-
eration of a mental health disposal). The psychiatrist must then make a judgement whether it is in the best interests of the evaluee for sufﬁ  cient information to be provided to the Court to alert them 
of the doctor’s concerns. Such disclosure will almost certainly be justiﬁ  ed in the interests of a fair trial and justice. The doctor will 
also have a duty to consider whether steps ought to be taken to undertake a Mental Health Act assessment (British law) to enable transfer to a hospital for medical treatment.
The other situation where a breach of conﬁ  dentiality may be jus-
tiﬁ ed is where a report is not disclosed but the report writer believes

tiﬁ ed is where a report is not disclosed but the report writer believes 
that the Court ought to consider the report’s ﬁ  ndings on potential 
risk to the public. In B.W. v Edgell and Rv Crozier, the Court held that the doctor’s duty of conﬁ  dence did not prevent a psychiatrist 
from taking steps to communicate the grounds of concern to the court. The strong public interest in disclosure to prevent a court from making decisions based upon inadequate information was held to override the psychiatrist’s duty of conﬁ  dentiality. Where a 
doctor is considering disclosure in these circumstances, advice should be sought from an experienced colleague, case law, and reg-ulatory body guidance consulted and the doctor should seek advice from their indemnity insurer.
Appearing in court

Advice on practical matters concerning a Court appearance is beyond the scope of this chapter but guidance is available (see recommended reading). Those undertaking regular expert work should consider courses which prepare them for appearance in Court and should understand the legal framework for giving oral evidence in court.
(21)
The cardinal rule when giving oral evidence in Court is that 
although called by one party, the expert witness is not giving evi-dence for that party’s side but is under a duty to provide fair and impartial evidence to the Court even where this conﬂ  icts with the 
interests of the party calling them.
In Criminal Courts, the defendant gives evidence before expert

In Criminal Courts, the defendant gives evidence before expert 
evidence is heard. Experts are allowed, unlike witnesses of fact, to sit in Court and hear the evidence of other witnesses before they, themselves, give evidence. An expert can be called by any interested party in proceedings.When calling an expert witness, the advocate must elicit the 
following
(21):
1 The expert’s qualiﬁ  cations: If the report has been prepared 
according to criminal procedure rules, the report will contain a biography setting out the qualiﬁ  cations and experience of the 
witness. It will then be usual for the advocate to lead this part of the evidence by reference to the biography supplied in the report. It will be perfectly permissible for the other side to call into question the expert’s qualiﬁ  cations. This should be met 
politely by outlining the reasons why the expert believes they have the requisite qualiﬁ  cations and experience to answer the

politely by outlining the reasons why the expert believes they have the requisite qualiﬁ  cations and experience to answer the 
questions posed in instructions.
2 Disclosure of the expert’s report: The report will have been 
pre-read by the Judge and it is usual for the examiner to refer to relevant sections of the report. A report with numbered para-graphs is easier for the Court to follow. The jury will not have read the report and will not usually be given sight of the report. Their knowledge of the expert’s report will come from submis-sions made by either side and through the Judge’s questioning and summing up.
3 Advocates are under a duty to challenge disputed evidence.
 Thus where more than one expert opinion is provided and they 
differ; the expert must expect their opinion to be disputed. The expert must resist pressure from one party to deviate from or express greater certainty about an opinion they have reached in the written report.

4 An expert witness may be cross-examined as a hostile witness if 
there is good reason to suppose that they are not telling the truth. Thankfully this is extremely rare. The possibility of delib-erate or inadvertent bias must, however, always be considered.
Expert Witness Institute. (2006). Experts in the civil courts . Oxford 
Hodgkinson, T. and James, M. (2007). Expert evidence: law and practice
(2nd edn). Sweet and Maxwell, London (detailed legal textbook on law 
relating to expert witnesses).
Holburn, C.J., Bond, C., Solon, M., et al.  (2000). Healthcare professionals as 
witnesses to the court , Greenwich Medical Media, London (practical 
advice on reports and appearing in court).
Omerod, D., and Hooper, A. (2008) Blackstone’s Criminal Practice 2009 .
Oxford University Press, Oxford (standard textbook on criminal law, frequently revised).
Weinstock, R. (2003). Part 1. History and practice of forensic psychiatry.

Weinstock, R. (2003). Part 1. History and practice of forensic psychiatry. 
1-94. In Principles and practice of forensic psychiatry  (2nd edn) 
(ed. R. Rosner), pp. 56–72. Arnold, London.(for a USA perspective)
See also references 9 and 20 below
1. O’Grady, J.C. (2002). Psychiatric evidence and sentencing: ethical 
dilemmas. Criminal Behaviour and Mental Health ,12, 179–84.
2. O’Grady, J.C. (2002). Report writing for the criminal court. 
Psychiatry ,6, 11.
3. Murphy, P . and Phillips, J. (2007). F10 expert opinion evidence. 
In Blackstone’s criminal practice 2007 , Section F10, pp. 2449–63. 
4. Ormerod, D. and Roberts, A. (2006). The admissibility of expert 
evidence. In Witness testimony  (eds. A. Heaton - Armstrong, 11.15  the expert witness in the criminal court: assessment, reports, and testimony

SECTION 11  forensic psychiatry 2008
E. Shepherd, G. Gudjonsson, and D. Wolchover), Chap. 22, pp. 401–24, 
 5. Hodgkinson, T. and James, M. (2007). Introduction: the principles and 
development of expert evidence. In Expert evidence: law and practice
(eds. T. Hodgkinson and M. James), Chap. 1, pp. 1–43, Sweet and Maxwell, London.
 6. Sales, B.D. and Shaman, D.W. (2007). Science, experts and law: 
reﬂ ections on the past and the future. In Expert psychological testimony 
for the courts  (eds. M. Costanzo, D. Krauss, and K. Pezdek), Chap. 2, 
pp. 9–30, Lawrence Erlbaum Associates, Mahwah, New Jersey.
 7. Hodgkinson, T. and James, M. (2007). Expert evidence: the future. 
In Expert evidence: law and practice  (eds. T. Hodgkinson and M. James), 
Chap. 28, pp. 645–9, Sweet and Maxwell, London.
 8. Ministry of Justice. (2005). Part 33: expert evidence. In Criminal 
procedure rules . Ministry of Justice, London. Available at: http://www.

dca.gov.uk/procedurerules.htm
 9. Rix, K.J.B. (2008). The psychiatrist as expert witness: Part 1. General 
principles and civil cases. Advances in psychiatric treatment .
10. Burn, S. and Thompson, B. (2006). Single joint expert. In Experts in the 
civil courts  (ed. L. Blom-Cooper), Chap. 5, pp. 57–76. Oxford University 
11. Stone, A.A. (1984). The ethical boundaries of forensic psychiatry 
- a view from the Ivory tower. Bulletin of the American Academy of 
Psychiatry and the Law ,12, 209–19.
12. Appelbaum, P .S. (1997). A theory of ethics for forensic psychiatry. 
Journal of the American Academy of Psychiatry and the Law ,
25, 233–47.
13. Royal College of Psychiatrists. (2004). The psychiatrist, courts and

13. Royal College of Psychiatrists. (2004). The psychiatrist, courts and 
sentencing: the impact of extended sentencing on the ethical framework of forensic psychiatry College Report 129 . Royal College of Psychiatrists, 
London. Available at:http://www.rcpsych.ac.uk/publications/collegereports.aspx14. Weinstock, R., Leong, G.B., and Silva, A. (2003). Ethical guidelines. 
In Principles and practice of forensic psychiatry  (2nd edn) (ed. R. 
Rosner), pp. 56–72. Arnold, London.
15. Feeley, M. and Simon, J. (1992). The new penology: notes on an 
emerging strategy of corrections and its implications. Criminology ,
30, 449–74.
16. Calvedeno, M. (1999). The psychiatrist as Gaoler. Journal of Forensic 
Psychiatry ,10, 525–37.
17. Beauchamp, T.L. (1999). The philosophical basis of psychiatric ethics. 
In Psychiatric ethics  (3rd edn) (eds. L.S. Bhoc, P . Chadoff, and

In Psychiatric ethics  (3rd edn) (eds. L.S. Bhoc, P . Chadoff, and 
S.A. Green), pp. 25–47, Oxford University Press, Oxford.
18. Mullen, P .E. (2007). Dangerous and severe personality disorder and in 
need of treatment. The British Journal of Psychiatry ,190, s3–7.
19. Hart, S.D., Michie, C., and Looke, D.J. (2007). Precision of actuarial risk 
assessment instruments: evaluating the ‘Managing of Error’ of group 
v individual predictions of violence. The British Journal of Psychiatry ,
190, s51–9.
20. Rix, K.J.B. (2008). The psychiatrist as expert witness: part 2. Criminal 
cases and Royal College of Psychiatrist’s guidance. Advances in 
Psychiatric Treatment ,14, 109–14.
21. Hodgkinson, T. and James, M. (2007). The expert witness at trial. 
Chap. 6, pp. 163–82. Sweet and Maxwell, London.
Case law

Case law
R v Turner [1975] Q.B. 834 and 841
GMC v Meadows [2006] EWCA Civ 1390
Daubert v Merrell Dow Pharmaceuticals Inc [1993] 509 US 575Ikarian Reefer [1993] 2 Lloyds Rep 68 at 81
R v Edgell [1990] Cr App ch 359
R v Crozier [1990–1991] 12 Cr App(s)206

It has been shown that the prevalence of mental illness among 
those in the criminal justice system is signiﬁ  cantly greater than that 
found in the general community.(1,2) As presented in Chapter 11.4, 
for example, the per capita rate of psychotic illness in prisons is approximately 10 times greater than that found in the general community. Tragically, relatively few services exist that provide continuity of mental health care between gaols and the community.
(3)
This produces a situation where individuals whose mental illness may have been identiﬁ  ed and treated in gaol ﬁ  nd themselves 
without services in the community. Typically, only when in crisis do they ﬁ  nd their way into general psychiatric services either in 
community settings or in hospital. This situation has produced considerable stress on already taxed mental health services.
(4)
Given the prevalence of offence histories among psychiatric

(4)
Given the prevalence of offence histories among psychiatric 
patients, it is important for mental health professionals to be aware of the unique issues—and myths—that accompany patients with offence histories. At the outset it is important to emphasize that the duty of mental health services is to address mental health issues. That ought to be the focus of mental health services. As this chapter makes clear, though, for some patients, there is a rela-tionship between the mental illness and offending and by address-ing the mental illness, the risk of re-offending might well be reduced. Moreover, many of the ancillary issues that lead to relapse and destability in psychiatric patients also may lead to offending. Addressing these issues will both help provide long-term stability for patients and will help reduce their risk of offend-ing. As a result, there is a need for general mental health services 
to acquire expertize to identify and manage patients with offend-
ing histories.

(5)
This chapter will provide information about the relative risk of 
offending among psychiatric patients and the relationship (or lack thereof) of inpatient aggression and community-based violence and offending. A framework will be provided for assessing and treating patients with offending histories and issues using a typol-ogy of mentally ill offenders. The role of forensic mental health services in bolstering general psychiatric services, and in sometimes providing primary care for mentally ill offenders, will also be discussed.How many patients have criminal histories?

Surprisingly little research exists that investigates the number of patients entering general psychiatric services who have an offence history. For reasons having to do with privacy, lack of perceived relevance, and professional reluctance, general mental health services do not consistently obtain reliable information regarding patients’ offence histories. This is often the case even when the patient has a current community-based corrections order. The two following studies can help shed light on the question of how many general psychiatric patients have histories of criminal offending.
In a study that was conducted to investigate the post-discharge 
violence of psychiatric patients and the predictive validity of risk assessment measures among almost 193 involuntarily committed psychiatric patients in British Columbia, Canada who were dis-
charged to the community, Douglas, Ogloff, Nicholls, and Grant
(6)
obtained ofﬁ  cial criminal histories for all patients who had ever

(6)
obtained ofﬁ  cial criminal histories for all patients who had ever 
been arrested or convicted of any criminal offence. The vast major-ity of patients had prior psychiatric hospitalizations (n =184, 95 per 
cent). Informally, members of the hospital staff were asked what percent of patients they believed had a prior criminal history. Staff, including psychiatrists, estimated that a very small percent of patients would have been arrested or convicted of offences—less than 20 per cent. The review of criminal histories, however, showed that 64 per cent (n =123) of patients had previous arrests or convic-
tions for any type of criminal offence, including 40 per cent (n =78)
who had been arrested or convicted of violent offences.
In an Australian study based upon Victorian samples of cohorts 
of patients with schizophrenia, Wallace and colleagues have found 
that almost 22 per cent of patients with schizophrenia have a

that almost 22 per cent of patients with schizophrenia have a 
history of offending at some point in their lives.
(7) Moreover, eight 
percent of patients with schizophrenia had a criminal conviction for a violent offence. These percentages increased three-and-four fold when the patients with schizophrenia also had a known sub-stance abuse problem. In a recent study, Hodgins and Muller-Isberner
(5) found that one quarter of patients discharged from 
a general mental health service had a criminal record.Managing offenders with 
psychiatric disorders in general psychiatric services
James R. P . Ogloff11.16

SECTION 11  forensic psychiatry 2010
While it is difﬁ  cult to know exactly how many psychiatric patients 
across different services have committed offences, the point that may be drawn from the above research suggests that many patients have offence histories—likely more than mental health profession-als would expect. The starting point of the chapter, therefore, is that while most psychiatric patients will not have violent criminal his-tories, many will have offence histories, including the commission of violent offences. Moreover, many more patients will have exhib-ited violent behaviour that did not lead to arrest or conviction. Therefore, even if they do not realize it, all psychiatrists and other mental health professionals have experience working with patients who have offence histories.
What leads mentally ill people to offend?

Although the reasons that anyone—including psychiatric patients—offends are myriad and complex, a typology of mentally ill offend-ers is helpful for understanding the reasons they offend.
(1) There 
are three general categories of people with mental illness who offend; understanding the general mentally disordered offender type will enable clinicians in general psychiatric services to provide appropriate treatment. The ﬁ  rst, and smallest group, includes 
those psychiatric patients for whom a necessary and sufﬁ  cient 
cause of their offending is the presence of their mental illness and the symptoms the illnesses produce. The second group includes patients who do not offend because of their mental illnesses, per se , but due to the concomitant social difﬁ  culties that all too 
often accompany mental illness. The ﬁ  nal general group of offenders

often accompany mental illness. The ﬁ  nal general group of offenders 
with mental illness include those patients whose offending occurs irrespective of their mental illness. Each of these groups will be described below.
Patients who offend because of their mental illness
This group is likely the smallest of the three groups. This group includes people who may not be criminally responsible because, as a result of their mental illnesses, they do not know what they are doing, or do not appreciate that what they are doing is wrong. Their offences occur as a direct result of the mental illness. But for the mental illness and the presence of symptoms which led to the patient’s offending behaviour, the crime would not have occurred. Their mental illness is both a necessary and sufﬁ  cient explanation

for their offence. They only offend when they are acutely unwell and the offence behaviour is a product of their mental illness (e.g. acting on delusions or hallucinations). Depending upon the jurisdiction in which they reside, they may be found not guilty by reason of insanity or mental illness. They most likely will be housed in secure hospitals rather than prisons following legal adjudication. 
Typically the illnesses that are present in people who fall into this 
category are psychosis or serious affective disorders accompanied by psychosis. Many jurisdictions that retain some form of insanity 
defence speciﬁ  cally exclude the use of the defence by those with 
antisocial or dissocial personality disorder.
1 Readers are referred to Chapter 11.3.1 (Associations between Psychiatric 
Disorder and Offending by Thomson and Darjee) for additional information regarding the relationship between mental illness and offending.Patients who offend as a result of the sequelae of 

The second general group of psychiatric patients who offend com-
prises hose whose mental illnesses are a necessary but not sufﬁ  cient

explanation for their offending. It is by far the largest group of psy-chiatric patients who offend. As is typical for many patients with serious mental illnesses, these patients begin to spiral downward socially as a result of their mental illnesses. They can become estranged from family and pro-social support networks. Their lives become unstable; housing, basic needs, and their need for non-judgmental personal support may go unmet. They may end up being accepted by groups of people who are themselves unstable. They often resort to engaging in illicit drug abuse. These social factors contribute to their resultant offending. While their mental illness may be a catalyst in the course of events that lead to the offending, the mental illness itself is not the direct cause of the offending. Had they not had a mental illness, they likely would not have begun offending. However, by the time they develop offending behaviour, their lives have become so disorganized and their maladaptive

Had they not had a mental illness, they likely would not have begun offending. However, by the time they develop offending behaviour, their lives have become so disorganized and their maladaptive coping and survival strategies have become so entrenched as to make the reversal of these processes difﬁ  cult over

the long-term. Psychiatric treatment, while a necessary starting point, will not be sufficient alone to eliminate the offending behaviour.
Patients who offend despite their mental illness
The ﬁ  nal group of patients are those who would offend irrespective 
of the fact that they have a mental illness. Although not as large a group as the one above, many more patients who offend fall into this category than into the ﬁ  rst. The fact that they have a mental 
illness is neither a necessary or sufﬁ  cient explanation for their 
offending. Patients in this group are typically characterized by early onset antisocial and illegal behaviour. They differ from other mentally ill offenders by having a pervasive and stable pattern of offending regardless of their mental state.
(5) This behaviour almost

(5) This behaviour almost 
always precedes the onset of mental illness. While people with a psychopathic or dissocial personality disorder will be included in this group, most of the people in the group will not be so disor-dered. It is important to acknowledge, though, that the broad range of people that may fall into this group, including the psychopaths, may well develop psychiatric illnesses. We must avoid the tendency to deny this group proper services or to acknowledge their mental illnesses. These patients’ mental illnesses may well exacerbate their offending or lead to unusual offending; however, even when they are asymptomatic they may continue to offend.
Aren’t psychiatric patients with offence 
histories unusually burdensome or too dangerous for mental health services?
The perception all too often still exists that patients with offence

The perception all too often still exists that patients with offence 
histories are unusually burdensome or even too dangerous to be seen by general mental health services. While there are doubtless patients, largely those drawn from the third group above, who are burdensome and even dangerous, in the main patients with offence histories are nether unduly burdensome nor dangerous. For exam ple, 
in a recent prospective study of violence among discharged general and forensic psychiatric patients, Doyle and Dolan
(8) found no

2011
signiﬁ  cant differences in post-discharge violence rates (both ofﬁ  -
cial and unofﬁ  cial) between patient groups in the UK. Ogloff and 
colleagues have obtained similar results from separate studies of post-discharge violence among samples of general and forensic psychiatric patients.
(6)
One of the concerns expressed in general psychiatric services 
about patients with offence histories is the risk for aggression and violence they might present during hospitalization. It is often assumed that if a patient has an offence history, particularly one marked by aggression, that the patient will be more likely to be aggressive in hospital. Research suggests, however, that this may not be the case. It is true that over the entire period of hospitalization patients who have more psychopathic traits might have higher rates of aggressive incidents.
(9) Research shows that in fact there is no 
signiﬁ  cant relationship, at least for forensic psychiatric patients,

signiﬁ  cant relationship, at least for forensic psychiatric patients, 
between aggression in hospital, aggressive behaviour preceding admission, or violent recidivism.
(10)
Analyses of what leads to aggressive behaviour by psychiatric 
patients suggests that dynamic (highly changeable) factors are responsible and that a functional analysis of inpatient aggression shows that rarely are the acts related to general patient aggression or purely to the patients’ mental state.
(11) Rather than assuming 
that patients with forensic histories will be any more or less aggres-sive than other patients, recent instruments have found useful in assessing patients risk for inpatient aggression.
(12) Such instruments 
should be employed.
Assessment of psychiatric patients 
who offend
Prior to commencing ongoing mental health care to patients with

who offend
Prior to commencing ongoing mental health care to patients with 
offence histories, it is important that a comprehensive assessment be conducted, preferably by a psychiatrist or clinical psychologist with expertize and experience in forensic mental health. In some jurisdictions, mental health services may be able to draw upon forensic mental health services to obtain secondary assessments of the patients to assist with assessment and treatment planning.
(13)
The assessment must address three major components: mental health, substance use, and the presence of criminogenic factors (i.e. factors that increase the likelihood that the patient will re-offend).
First, a thorough mental health assessment is required that

First, a thorough mental health assessment is required that 
includes both a review of the patient’s current mental state as well as their psychiatric history. Although seemingly straight-forward, this can be difﬁ  cult with some patients who have offence histories. 
All too often now we see young people, usually males, whose men-tal illnesses are only identiﬁ  ed upon admission to gaol or prison.
(3)
As such, it may be difﬁ  cult to obtain reliable information about the 
genesis and onset of these people’s mental illnesses.
The second component that must be considered is whether the 
patients have a substance use or dependence disorder and what role substances have on their mental illness and offending. In mental health generally,
(14) and in patients with offence histories in 
particular,(15) high percentages of patients are substance abusers.

particular,(15) high percentages of patients are substance abusers. 
Ogloff and colleagues found that 74 per cent of patients in the secure forensic hospital in Victoria, Australia had a lifetime history of substance abuse or dependence. The presence of a substance use disorder is a key risk factor in determining which patients will re-offend (or have a relapse of their illness for that matter). Unfortunately, very often substance use disorders, and their effects 
on patients, are overlooked in the routine assessment and treat-ment of patients with mental illnesses.
The ﬁ  nal area that must be considered in a comprehensive assess-
ment is the presence of so-called ‘criminogenic factors’ present in the patient’s case. This concept is part of a contemporary well accepted and supported theory of offending known as the Psychology of Criminal Conduct, which was developed by Andrews and Bonta in the 1980s and it has been reﬁ  ned over time.

(16) It is 
a theory concerned with individual differences and variability in criminal behaviour, making it a particularly useful guide for both assessing the risk of reoffending and planning rehabilitation attempts. This emphasizes the complexity of criminal behaviour, thereby acknowledging the contributions of social context, biology, and psychopathology. Criminogenic factors are the subset of dynamic (changeable) risk factors that have been found to relate directly to a risk for re-offending. They are therefore modiﬁ  able 
characteristics, whereby a change in the risk factor equates with a change in the risk of re-offending. These are factors that can affect patients with mental illness just as they can affect people with no mental illness who offend. Examples include having friends who are criminals, developing pro-criminal attitudes, having an anti-social personality, having limited problem-solving skills, and having difﬁ  culties controlling anger and hostility (Ogloff &

Davis, 2004).
(17)
T o assist in assessing Andrews and Bonta(18) have developed the 
Level of Service Inventory, Revised  (LSI-R), which assesses the pres-
ence of criminogenic factors as the basis for offender assessment and treatment.
1 The LSI-R consists of 54-items “grouped into the 
following domains or sub-components (with the number of items in parentheses): Criminal History (10); Education/Employment (10); Financial (2); Family/Marital (4); Accommoda tion (3); Companions (5); Alcohol/Drug Problems (9); Emotional/Personal (5); and Attitudes/Orientation(4).
(18) While developed for general 
criminal populations, the LSI-R has been found very useful for assessing the presence of criminogenic factors and general needs of psychiatric patients with offending histories. Recent research ﬁ  nd-
ings show that a screening version of the LSI-R reliably identiﬁ  es 
risk factors for patients in forensic psychiatric services.
(19)

(19)
The presence of antisocial personality or dissocial personality is a 
criminogenic factor that must be considered in the assessment of mentally ill offenders. Unfortunately, antisocial personality disorder as it is deﬁ  ned by the Diagnostic and Statistical Manual of Mental 
Disorders, Fourth Edition, T ext Revision
(20) is vastly over-represented 
in psychiatric populations due to the nature of the criteria for the disorder which are essentially the presence of criminality.
(21) Thus, 
great care must be taken to ensure that the diagnosis of antisocial personality does not rely solely on the fact that the patient has a history of offence behaviour. Instruments designed to reliably measure the presence of psychopathy, such as the Psychopathy 
Checklist , can be useful for assessing the aspects of personality and 
behaviour that comprise psychopathy.

(21, 22)
Following the assessment of each of the above components, it 
is necessary to develop a formulation that considers where the 
1 There is a revised version of the LSI-R which includes a section for 
case management planning, the Level of Supervision/Case Management Inventory and a version for young offenders (Y outh Level of Service/Case Management Inventory; Hoge, Andrews, & Leshied, 2002).11.16  managing offenders with psychiatric disorders in general psychiatric services

SECTION 11  forensic psychiatry 2012
patient’s mental illness factors into their offending. Drawing on the 
three typologies of offenders with mental illnesses outlined above, the clinician can determine which category best describes the patient. Because the typologies are general, there will be overlap in characteristics for some patients. In addition to understanding the factors that help explain a patient’s offending, the typologies are very important for determining what treatment and management strategies can be most effective for the patient.
The treatment of mentally ill offenders by 
general mental health services
The typology of mentally ill offenders will be revisited below with 
respect to the mental health and related services they require to assist with their treatment and management. The three-prong assessment strategy brieﬂ  y described above will be helpful to iden-

tify the range of treatment needs the patient has. T o be clear, the primary and even sole purpose of general mental health services is to treat patients’ mental illnesses. However, it is useful to consider the presence of an offence history as an indication of the patient’s functional impairment. Depending on the group into which the patient falls, the relative efﬁ  cacy of mental health services alone 
varies in the extent to which it will satisfactorily address their men-tal health and offence issues. Most often, particularly for the latter two groups below, ancillary services and forensic mental health services will be required to help ensure the patient’s long-term 
stability and to reduce the likelihood of offending.

Although this group of patients may commit horrendous acts,

Although this group of patients may commit horrendous acts, 
it is as likely that they engage in nuisance offences. Despite the particular type of offending behaviour in which they engage, perhaps surprisingly, their management by mental health services is oftentimes less complex than is the case for the other two groups of offenders with mental illnesses to be discussed below. Generally speaking, the treatment that this group requires is conventional mental health care. As it is the case that the primary cause of their offending behaviour is the mental illness, and the symptoms that it produces, addressing their mental health needs can serve to elimi-nate the offending. General mental health services are generally well equipped to deal with these patients, though they may feel reluctant to do so. Very often, patients will respond to medication and with supervision their mental state will begin to improve. If

treatment in the cases is complex, it will often be because of the 
mental illness itself. For example, the patients may have chronic 
psychosis which is refractory to psychiatric treatment.
While the patient’s mental illness is the main cause of the offending
behaviour in this category, related issues will need to be addressed to stabilize the patient over the long term and to further reduce the patient’s risk of re-offending. The LSI-R, noted above, will be par-ticularly helpful in identifying such issues. Common issues include substance abuse, life skills, housing, ﬁ  nancial support, and personal 
support. Services to address these issues will need to be organized to effect long-term psychiatric and behavioural stability.
Patients who offend as a result of the sequelae of 
Just as the complexity of the reason this group offends is greater

Just as the complexity of the reason this group offends is greater 
than with the ﬁ  rst group, the treatment they require to stabilize is also more complex. This group is characterized by general disor-
ganization and social damage. As such conventional mental health services alone will have relatively limited effect on patients’ mental state and stability over the long-term. Even if psychiatric treatment is effective in the short-term, patients in this group will be likely to return to a chaotic life which eventually may include a return to offending. Nonetheless, the treatment of these patients’ psychiatric illnesses is the central component of their care.
The comprehensive assessment approach outlined above will 
be particularly useful in determining the range of issues beyond mental illness that affects the patients and contributes to their 
offending behaviour. In particular, the areas of concern identiﬁ  ed

offending behaviour. In particular, the areas of concern identiﬁ  ed 
by the LSI-R are particularly important for informing intervention need. For example, if employment issues, ﬁ  nancial issues, accom-
modation needs and alcohol/drug problems are revealed in the assessment, these issues, in addition to the patient’s mental illness will need to be addressed. Not only will addressing these issues satisfactorily lead to a reduction in the patient’s risk of re-offending, but it will assist with ensuring stability in mental state over the long-term.
Generally speaking, the greater the number of criminogenic

Generally speaking, the greater the number of criminogenic 
factors that arise from the assessment, the more intensive treatment will need to be to ensure long-term stability. T o the extent that needs arise that cannot be addressed directly by the mental health service, these services will need to be sought from appropriate pro-viders in the community. This is where effective case management and service brokerage is critical. All too often psychiatric patients revolve in and out of general mental health services (and the cri-minal justice system); all the while their underlying needs are not identiﬁ  ed or addressed. The vast majority of offenders with mental

illnesses can be properly treated and managed by general mental health services if only their related needs and issues can be addressed. Moreover, given that there is a relationship between these patients’ mental illnesses and their offending, addressing the mental illness and related matters can help lead to a reduction in offending, although that will not be the purpose of providing them with general mental health services.

As with all of the categories of offenders, this group will still require comprehensive mental health care; however, the mental health care will be essentially futile in reducing the patient’s proclivity for offending. It is important to note that mental health services still have an obligation to treat these patients’ mental illnesses, but addressing their offending issues will be beyond the scope of care or even the expertize of general mental health services. Moreover, addressing the ancillary issues that arise to affect their mental ill-nesses will be less likely to reduce their offending risk than would be the case for either of the other two groups above. Where possi-ble, patients in this group should be seen by forensic mental health services and they will be candidates for offender rehabilitation programmes offered by contemporary correctional services (in prisons or in the community).

It is important to note that the cautious approach advised is not 
intended to dissuade services from providing adequate psychiatric care, but to recognize their limitations and to reduce the sense of failure and frustration that occurs when treating patients with such an offence pattern. Despite the nihilism that sometimes exists, there is an ever expanding corpus of ﬁ  rm empirical support to

2013
show that offender rehabilitation can help reduce recidivism,(17,23)
however, such services are beyond the scope of general mental 
health services. Over time, of course, as these patients’ offending issues may be successfully addressed, they will be appropriately cared for by mental health services just as other people are. Once an offender not always an offender!
The role and support of forensic mental 
The thorny question of when forensic mental health services, as 
opposed to general mental health services, ought to be responsible for a patient’s psychiatric care is difﬁ  cult and depends much on the

opposed to general mental health services, ought to be responsible for a patient’s psychiatric care is difﬁ  cult and depends much on the 
jurisdiction, the relevant legislation, policies, and practices that are in place. It is never the case that all patients who offend require, or should have access to, forensic mental health services. For the most part, the goal should be to maintain patients in general mental health services to ensure continuity and normality of care. Realistically, though, given the relatively high rate of psychiatric patients who offend or who have offence histories, the level of knowledge and awareness of offence issues among general mental health professionals must increase.
It is still the case in many settings that the mere mention that 
a patient has a forensic history raises angst and concern about the capacity of general mental health services to care for the individual.

a patient has a forensic history raises angst and concern about the capacity of general mental health services to care for the individual. 
This is most often nonsensical, particularly because a relatively high percentage of psychiatric patients in general services have 
an offence history—whether or not it is known by the service. Ideally, general mental health services should adequately address patients’ mental health and ancillary issues to an extent that would actually prevent patients in the ﬁ  rst two groups of mentally ill 
offenders from offending. Very often we in forensic mental health services see patients who had contact with general mental health care yet their problems were exacerbated, they deteriorated and went on to offend. Oftentimes inadequate assessment and identiﬁ  -
cation of the patients’ needs is at the core of the shortcoming of their care.
Realistically, despite the oftentimes excellent care provided to

Realistically, despite the oftentimes excellent care provided to 
psychiatric patients, forensic mental health services will be required. In the ﬁ  rst instance, patients found not criminally responsible or 
who require involuntary treatment during incarceration should be provided service in appropriate forensic mental health facilities. Psychiatric patients with complex presentations, including myriad criminogenic issues, likely will require at least secondary consulta-tion from a forensic mental health service.
(13) The best models that 
exist internationally have forensic mental health services take responsibility for the complex offence-related cases initially with the introduction and eventual transition to general mental health services over time once the patient’s offending issues are addressed and stability is realized.
(24,25)  Continuing general care is the preferred

(24,25)  Continuing general care is the preferred 
modality of care except in the most difﬁ  cult cases.
General psychiatry has an important role in providing care to all 
patients, and under most circumstances this includes patients with offending histories and issues. Given the relatively high rates of offending among psychiatric patients, whether they realize it or not, general services have considerable experience with this patient group. All too often, though, general mental health clinicians do not 
have adequate training or expertize to systematically assess patients to determine what factors have lead to their offending. The typology of patients who offend presented in this chapter can prove useful for determining the factors that must be addressed to treat the patient. Moreover, an indication will be made as well when assist-ance may be required by specialist mental health services.

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Philosophy and theoretical models
Specialist forensic mental health (fmh) services are for people 
with serious mental disorders and grave offending behaviour who tend to be rejected from mainstream services. Although often triggered by single high proﬁ  le cases, these specialist services are 
among the best planned and commissioned services in psychiatry, founded in evidence of need, risk and efﬁ  cacy of interventions. 
They are grounded in a multidisciplinary clinical perspective and often have integrated academic units. They interface both with other clinical services and with the criminal justice service. Good relationships with the local community are vital for establishment and growth.
Mentally disordered offenders have been sources of tension 
between services at least since the early 19
th century. In Britain, the

th century. In Britain, the 
Lunacy Commission argued that it was ‘highly objectionable’ that offender patients should be detained in a general lunatic hospital, while an 1807 parliamentary select committee noted that ‘to conﬁ  ne lunatics in a common Gaol is equally destructive of all 
possibility of the recovery of the insane and the comfort of other prisoners’ .
(1) High security hospitals followed about 50 years later.
Funding and commissioning of fmh services worldwide contin-
ue to follow oscillations between considered responses to changes in the structure and availability of general services, and responses to single notorious cases. For England and Wales, the Butler Report
(2) considered the then increasing gaps in service provision 
as psychiatric services shifted from mainly institutional to mainly community care. It was the most thoughtful and powerful driver of

as psychiatric services shifted from mainly institutional to mainly community care. It was the most thoughtful and powerful driver of 
modern forensic mental health services in England and Wales, presaging the arrival of medium security hospital units. The 
contrasting path, of case driven service development, is illustrated by the so-called ‘Dangerous and Severe Personality Disorder’ (DSPD) services,
(3) driven by the inquiry into the care and treat-
ment of Michael Stone(4) following his conviction for two homi-
cides and an attempted murder, occurring soon after his discharge from a psychiatric hospital. In the USA, mandated community mental health law (Kendra’s Law) and treatment programmes in New Y ork followed a subway killing by a psychotic man,
(5) while 
legislative change necessary for specialist service development in Japan followed a school massacre.(6) Concern that single cases

(5) while 
legislative change necessary for specialist service development in Japan followed a school massacre.(6) Concern that single cases 
make poor law – and poor health reforms—is tempered by the mutual commitment of government agencies and of practitioners to keep offender patient services under review.
The Department of Health and Home Office report, for 
England,
(7) is a good example of such review, proposing ﬁ  ve princi-
ples for secure healthcare provision:
 i) quality of care and proper attention to individual needs; ii) community rather than institutional care where possible;iii) security no greater than justiﬁ  ed by the danger presented—to 
self or others;
iv) maximization of rehabilitation and chances of sustaining an 
independent life in the longer term;
 v) proximity to the patient’s own home or family if s/he has 
them.
It is arguable that only the ﬁ  fth principle requires an evidence

them.
It is arguable that only the ﬁ  fth principle requires an evidence 
base. Intra-familial violence may contribute to mental health and/or behavioural difﬁ  culties, and most violence by people with men-
tal illness occurs within their close social circle.
(8) Nevertheless, 
people have attachments, and the ﬁ  fth principle is retained for that 
reason— and as a convenient way of anchoring responsibilities for 
services. The ﬁ  rst four principles embody the medical ethic of 
maximizing autonomy and anticipated the Human Rights Act 1998, which gives effect to the rights under the European Convention to liberty and security of person  (article 5) and prohib-
itsdegrading treatment  (article 3). The Act also emphasizes propor-
tionally—if it is necessary to breach a right, that breach should not go further than necessary.
Organizational models often founder in a clash between the

Organizational models often founder in a clash between the 
needs of service users and providers. The ideal is a fully integrated services in which service users move freely between forensic and general mental health services, according to need.
(9) General serv-
ices, however, tend to have to focus on crisis management, 
and the greater the tensions between specialist and general services the greater the likelihood of ever-longer periods of residency in a 
physically secure hospital
(10) or default to parallel service delivery Management of offenders with 
mental disorder in specialist forensic mental health services
Pamela J. Taylor and Emma Dunn11.17

SECTION 11  forensic psychiatry 2016
reasons for this include reduced availability of non-secure psychiat-
ric beds, perverse incentives in funding in which those in highest security may be funded centrally with minimal local funding bur-den. Also government caution may dictate that once detained in medium or higher security, every individual must progress stepwise through lower levels of security before returning to the community. Evidence does not support the notion that this stepwise route reduces criminal recidivism,
(10) but it has led to the growth of additional 
tiers of specialist security provision, including ‘low security’ hospital units and forensic community mental health teams.
The international context
There is insufﬁ  cient space to explore the international context in 
any detail. Laws on criminal responsibility, criminal justice and mental health vary between European countries
(11) and elsewhere,

(11) and elsewhere, 
but many underlying clinical principles are shared. Most countries acknowledge some association between mental disorder and offending behaviours, but there is variation in how this inﬂ  uences 
prosecution, ﬁ  tness to plead and stand trial, the extent to which 
mentally disordered offenders may be regarded as wholly or par-tially without responsibility for a criminal act, and the extent to which they are treated in mainstream or specialist secure health services, or in prisons, albeit with some health service input.
Our international research group (SWANZDSAICS) drawn from 
culturally distinct jurisdictions across ﬁ  ve continents (Sweden, 
Wales, the Australian state of Victoria, New Zealand, Denmark, the South African province of Western Cape, Japan, the Canadian province of Quebec, and Scotland) ﬁ  nds a shared therapeutic

Wales, the Australian state of Victoria, New Zealand, Denmark, the South African province of Western Cape, Japan, the Canadian province of Quebec, and Scotland) ﬁ  nds a shared therapeutic 
philosophy in managing offenders with psychosis, but struggles to be therapeutic with sex offenders or people with personality disorder.
(12) Other countries however, most notably the USA, seek 
to separate the business of psychiatry in the courts from any thera-peutic endeavour with mentally disordered offenders.
(13)
The nature of security
Secure psychiatric hospitals have two overarching aims: improving health and delivering safety for patients and others. In secure hos-pitals, patients’ autonomy is limited in a number of important ways: they may not be allowed to leave the hospital at all, may be conﬁ  ned to a particular area within the hospital, and/or treatment

may be enforced. Although these restrictions are undoubtedly at least partly in the interests of the patients themselves, they are commonly also in the interests of others.
The elements of security
Security in a clinical setting is made up of four main elements: 
physical, procedural, and relational security, and treatment. 
Treatment, including (re)habilitation, becomes vital to safety and 
security whenever a clear pathway can be shown between a mental disorder and offending behaviour.
Physical security  refers to the qualities of buildings: the nature of

Physical security  refers to the qualities of buildings: the nature of 
perimeter walls and internal structures and functions. High secu-rity requires at least one high and distinct perimeter wall or fence clear of the main hospital building. In medium-security, the walls of the building alone generally provide the main perimeter, with high fences only surrounding exercise areas which are not entirely within the main building. All specialist security hospitals provide for staff and visitor entry through an ‘airlock’ , using independent

locking systems, the external one generally controlled by dedicated security or administrative staff. Ideally, clinical staff contributing to building design, which should ensure good sightlines throughout, while allowing residents a sense of privacy. Each patient has his/her own room, and ideally holds a key to it (with a staff over-ride potential). This enhances his/her safety and sense of personal secu-rity, and also the safety of property. In high-security units, cameras may be used for continuous monitoring. The environment should be pleasant, enabling both patients and staff to feel comfortable; small frustrations often trigger violence.
Procedural security  provides for a formal set of checks for factors 
thought to be associated with risk of harm by patients. This includes minimizing patient access to weapons, ﬁ  re-setting materials, or

thought to be associated with risk of harm by patients. This includes minimizing patient access to weapons, ﬁ  re-setting materials, or 
potentially disinhibiting substances, and preventing absconding. In high security, any communication with the outside world may be monitored; at lower levels of security, such monitoring is deter-mined case by case. Procedures should also guard against potential harm to each patient. Some measures used to prevent or control 
violence may have ‘side effects’ . Time-out and seclusion may be 
necessary, but can be provocative and open to abuse. Physical restraint may sometimes be essential, but if done incorrectly or brutally may damage the possibility of a therapeutic relationship, physically harm or even kill the patient. In the UK, procedures for such measures are subject to guidance both from professional bodies
(14) and legislative Codes of Practice (e.g.(15)).
There is insufﬁ  cient space to detail the extensive range of proce-

dures for ensuring security, so a couple of examples—searching and screening of contacts—must sufﬁ  ce. Searches of the person 
and of the environment are conducted mainly to minimize access to drugs and weapons. The level of unit security dictates the nature, extent and frequency of searches. In English high security hospi-tals, no-one is trusted. Staff, professional visitors and social visitors are all searched on entry; many items—such as mobile/cell phones are forbidden anywhere in the hospital. Patients may be searched randomly, but also when moving between areas in the hospital or if there are particular grounds for suspecting they have secreted something that could become a weapon, or acquired drugs. At any security level, patient rooms and other areas may be searched— 
similarly, randomly or on specific grounds; in high security,

similarly, randomly or on specific grounds; in high security, 
patients’ possessions are routinely restricted in quantity to facilitate searching. For all such occasions, however, procedures incorporate measures which reﬂ  ect concern for the individual being searched. 
Patients must be informed of searches (immediately beforehand if randomly timed) and invited to observe.
Screening of contact with visitors is multifaceted. Visitors may be 
enticed into aiding absconsion, or be irresponsible in their ‘gifts’ for the patient; apparently innocuous items may be fashioned into weapons, and they may be under pressure to bring drugs, perhaps disguised in food. There may also be risk of harm to visitors. T elephone calls, mail and personal visits may all be observed, but only in accordance with written procedures. Policies pertaining to visits will refer to classes of visits—for example visits by speciﬁ  c

individuals who may threaten or be under threat, or by children, Such visits must be supervised by speciﬁ  cally trained staff.
Relational security  skills are founded in therapeutic approaches 
and, with speciﬁ  c treatments, form the core of hospital security, 
clearly demarcating hospitals from prisons. It lies in extensive knowledge of each patient, accurate empathy and highly developed

2017
capacities for communicating and working in a clinical team. At 
best, it not only provides immediate safety and the milieu for change, but it may also facilitate lightening of physical and proce-dural securities. Effectiveness, however, is reliant on sufﬁ  cient 
numbers of adequately trained staff.
Relational security may, however, create anxiety in hospital man-
agers and their political masters, partly because it is more difﬁ  cult to 
understand as security than locks and walls, but also due to the per-ception that its corruption is possible and difﬁ  cult to predict. Over 
time, staff may be vulnerable to potentially counter-therapeutic change.
(16) Strategies to ensure maintenance of clinical integrity 
therefore include personal supervision and appraisal, peer review and audit of team- and hospital-wide practice. Access to psychody-namic psychotherapists is not only, or even primarily, for the patients, but also for the staff and the institution.
(17)

(17)
Treatment as security  targets the link between symptoms of 
mental disorder, most obvious for psychotic symptoms, and crimi-nal or risky behaviour.
(18) In contrast to prisons, secure hospitals 
generally select residents for their treatability. It seems simple then—speciﬁ  c treatment with antipsychotic medication for people 
with psychosis should bring safety—but matters are rarely so straightforward. Multiple diagnoses are common: at least 25 per cent of offender patients with psychosis have personality disorders established before onset of their psychotic illness, and many abuse alcohol and/or other drugs at levels to qualify for a diagnosis.
(18)
Over 25 years, an increasing proportion of English high security hospital patients were found to have substance misuse disorders,
(18)
especially affecting the psychosis-personality disorder group. Substance misuse not fully meeting diagnostic criteria is also com-mon. In the short term, speciﬁ  c treatment for psychosis combined

especially affecting the psychosis-personality disorder group. Substance misuse not fully meeting diagnostic criteria is also com-mon. In the short term, speciﬁ  c treatment for psychosis combined 
with preventing access to substances of abuse can restore safety. For longer term success and safety, speciﬁ  c treatments aimed at sub-
stance misuse are best integrated as part of the overall treatment package,
(19) although this is still not common practice (e.g. UK,(20)
and Sweden,(21)). This may partly explain the counterintuitive 
ﬁ nding(22) that, in the UK at least, there is a preference for admit-
ting people with ‘pure’ psychosis to medium security hospitals, even though substance misusing people with psychosis would be regarded as a higher risk group (e.g.
(23)).
Hospital security in practice
In England and Wales, high security hospitals  are mandated in statute

(23)).
In England and Wales, high security hospitals  are mandated in statute 
for those patients who pose an imminent risk of serious harm to ‘the public’ . Public safety is often construed merely as removing dangerous persons from the community and strictly conﬁ  ning 
them. During the early stages of treatment adequate protection for staff and other residents is also vital. As patients become apparently safe, it is important that they can be tested out before discharge to the community, but government restrictions often make this difﬁ cult, so that patients may arrive at lower security levels ill-
prepared for the new challenges; this may be dangerous in itself.
Medium security  can be deﬁ  ned only in relation to high and low 
security services above and below it. The range, quality and quantity of low secure and open provision varies from place to place, so that providers of some medium secure service may have to retain patients

longer than other providers and/or provide more parallel services.
The most constant aspect of medium security services is the 
in-patient unit. ‘The aim is for the building design to support the nursing staff, who are the main security barriers.’
(24) Procedural security tends to be less stringent than in high security, but rela-
tional and treatment security are generally comparable. Nurse:patient ratios should be at least 2:1, and staff from a full range of other clinical disciplines should be available.
Low security  relies almost entirely on relational security, but units 
generally have a locked door, and some procedures relevant to security, such as monitoring of substance misuse.
Service structure
Planning principles
‘Pyramid planning ’ applies to specialist fmh services: the most

‘Pyramid planning ’ applies to specialist fmh services: the most 
intensive, specialized and secure services, most of which constrain patients’ liberty and are the most costly, should be the smallest and at the top of the pyramid. At the base of the pyramid, and greatest in number, should be services linked directly to the local commu-nity. Trends in service provision in England and Wales reﬂ  ect this 
model, with high secure bed numbers falling, and an increasing number of medium secure services (in mid-2007, 800 and 3 500 respectively for 55 million general population). Low security serv-ice provision is also increasing.
Private healthcare facilities.  It is generally regarded as unethical 
to proﬁ  t from the indeﬁ  nite institutional detention of people. In

to proﬁ  t from the indeﬁ  nite institutional detention of people. In 
Japan, where private provision of mental healthcare was the norm, recognition of service gaps for mentally disordered offenders resulted in the provision of publicly funded, purpose designed facilities for such patients.
(6) In the UK, independent provision 
supplements a shortfall in specialist NHS facilities, providing just under half of all forensic beds. There are several reasons for this, not least the greater ﬂ  exibility in service planning enjoyed by inde-
pendent than public sector providers. Nevertheless, all places for detained patients in the UK are publicly funded and independent service providers are subject to the same levels of scrutiny as NHS facilities.
‘Super-specialist’ provision  is necessary to provide speciﬁ  c treat-

ments and the appropriate milieu for people with some special needs, such as female offender-patients, who almost invariably have suffered prolonged and serious neglect and abuse through child-hood. Approaches founded in attachment theory
(25) or trauma 
based work(26) go some way towards meeting their needs. People 
with a learning disability also beneﬁ  t from dedicated services,(27) as 
may children and adolescents.
While there are advantages to specialist developments, most 
groups needing them tend to be small, and hence there are few units and it is difﬁ  cult for residents to retain close ties with home, 
e.g. women resident in the only English high secure provision may be more than 350 miles away from home.
Planning service capacity  is difﬁ  cult. It is often done from utiliza-
tion ﬁ  gures, but these tend to underestimate requirements by fail-

ing to recognize unmet need. While most developed countries have shifted general psychiatric services away from inpatient provision to the community, they have also seen an upsurge in availability of legal and illicit mind-altering substances. This has the probable effect of raising violence levels not only among the mentally healthy, 
but also among those with mental disorders (e.g.
(28)).
Prison populations are growing in many countries. In the 
USA and the UK indeﬁ  nite sentences ‘for public protection’ have 
been implemented. In England and Wales, the Lord Chief Justice and the Chairmen of the Parole Board have projected an additional 11.17  management of offenders with mental disorder in specialist forensic mental health services

SECTION 11  forensic psychiatry 2018
12, 000 prisoners under this sentence alone by 2012, all of whom 
will need some sort of ‘treatment’ before they can be released(29)
(at the time of writing a legal challenge to the lawfulness of such sentences in the absence of sufﬁ  cient treatment is underway). 
Surveys of mental disorder among UK prisoners(e.g.
(30,31) ) suggest 
that neither generic nor specialist mental health services have kept pace with need in prisons even before this new expansion.
Capacity planning must be dynamic, taking into account assump-
tions about other services, and socio-economic differences between communities. Statistical models may help, (e.g.
(32)) but it is more 
difﬁ cult to allow for changes in sentencing policy.
The service users: assessment, management, 
treatment and rehabilitation
Assessment in forensic psychiatry is considered in Chapter 11.14.

Assessment in forensic psychiatry is considered in Chapter 11.14. 
In some countries, such as the USA, assessments for the courts are the main tasks for forensic psychiatrists, with some specializing in just one type of assessment and few providing treatment services.
Pre-admission assessment is important for patients destined for 
a secure hospital. It informs the initial treatment plan, and ensures a safe case-mix and appropriate stafﬁ  ng. Patients admitted to a

a secure hospital. It informs the initial treatment plan, and ensures a safe case-mix and appropriate stafﬁ  ng. Patients admitted to a 
secure hospital must have a mental disorder which meets legislative criteria for detention. Security requirements are then based on assessment of both mental disorder and criminal/violent behav-iour. External factors must also be considered, for example, assess-ment of victim vulnerability. If, at one extreme, the identity of patient A ’s potential victim and the circumstances in which s/he might be at risk are clear, and that putative victim can acknowledge 
and co-operate with safety strategies, then it may be possible to manage risk of harm with little recourse to physical security. If,

and co-operate with safety strategies, then it may be possible to manage risk of harm with little recourse to physical security. If, 
however, patient B threatens named people who cannot under-stand, accept or help manage the threat, then physical security may initially be required for her, even though both patients are other-wise similar. A serious, more generalized threat may also mean that initial assessment must be in security.
Admission criteria
Broad agreement on criteria for admission to a secure hospital bed
(33) does not necessarily lead to consistency in practice.(22)
In England and Wales, only 40–50 per cent of people referred for a 
specialist secure hospital bed, whether in high(34) or medium secu-
rity(22) are actually offered one. There are common reasons: i) that

rity(22) are actually offered one. There are common reasons: i) that 
some disorders are not widely considered to be treatable, and ii) the high level of security requested is thought not to be necessary. In spite of powers in England and Wales to detain people with person-ality disorder for assessment or treatment, many medium security beds are effectively closed to them. Few are now admitted to high security hospitals, except to the new purpose designed ‘DSPD’ units. It seems to be only in the Netherlands that there is a prefer-ence for treating people with personality disorder in secure hospitals.
(35) There are few data on which to judge the 
quality of such assessments, but one study showed that 85 per cent of those refused a high security bed remained outside high security during the following 12 months, without incident.
(36)
There have been efforts to attain standard ratings of security

(36)
There have been efforts to attain standard ratings of security 
need. Cohen and Eastman(37) generated a set known as the Admission Criteria to Secure Services Schedule (ACSeSS). Factors 
considered relevant to admission were (* indicates factors most used in determining admission):
◆ gravity of recent* and past violence;
◆ likely immediacy of violence;
◆ psychopathology/developing behaviour possibly predictive of 
violence;
◆ special pathology, for example PD or sexual offending;
◆ the likely longevity of risk of violence*;
◆ predictability of the gravity and immediacy of potential future 
violence.
Collins and Davies(38) developed the Secure Needs Assessment 
Proﬁ le (SNAP), designed for clinicians  to operationalize clinical 
judgement, following the ﬁ  rst three elements of the security matrix 
outlined above—need for perimeter, and procedural or relational security.
The practice of using structured aids for clinical assessment

The practice of using structured aids for clinical assessment 
of risk of harm to others or to self is growing, with nursing staff finding them particularly attractive. The HCR-20 (20 item Historical and Clinical Risk Management instrument;
(39) includes 
dynamic risk factors, which can both inform management and provide a baseline measure from which progress can be monitored.
(40)
Progressing along the pathway to treatment.

(40)
When someone has one or more serious mental disorders and poses a serious risk of harm to others, assessment may become a lengthy process. The elements of this must in turn be evaluated and adjusted according to interim outcome measures. Figure 11.17.1 summarizes a typical pathway. The initial assessment is directed at establishing safety—either through advice to others, or through admission to a specialist setting. In the latter, the assessment merges seamlessly into engagement into treatment, directed ﬁ  rst at the 
primary disorder, before working with underlying factors—such as experience of childhood trauma.
The concept of ‘treatability’. Under mental health legislation for 
England and Wales, patients legally classiﬁ  ed as having psychopathic

disorder  or mental impairment  alone cannot be detained for treat-
ment in hospital unless ‘such treatment is likely to alleviate or prevent a deterioration’ of the condition. This intended safeguard against 
improper detention has sometimes been used to reject ‘difﬁ  cult’ 
patients. New mental health legislation does not distinquish disor-der types and puts the burden on availability of treatment.
Treatability should not be confused with curability. Assessment of

Treatability should not be confused with curability. Assessment of 
treatability should be made in full awareness of the assessor’s own attitudes and fears, with primary consideration given to the patient’s psychopathology, needs, insight, and preferences and motivation for treatment. The timing of such an assessment may also be crucial. If the consequence of no treatment is more-or-less certain, for exam-ple, imprisonment, and this will most likely cause deterioration, then this in itself could justify admission for hospital treatment.
Principles of treatment. First line treatment of mental disorder in a

Principles of treatment. First line treatment of mental disorder in a 
secure setting generally differs little from that used elsewhere in men-tal health services. It is important to be aware, however, that some treatments have never been systematically evaluated among people whose mental disorders are complicated by violence. For example,

2019
some consider that caution should be exercised in the use of cogni-
tive behaviour treatment to alleviate psychotic symptoms.(41)
Delivery of treatment  in secure conditions differs in some impor-
tant ways from its delivery elsewhere. Intrusive interventions are not unique to forensic mental health services, but the length of application means that staff may need to engage in regular peer and external review to ensure their work remains effective and ethical. Areas for concern include the creation of a climate of com-pulsion and coercion, and the conﬂ  icting roles for psychiatrists 
using therapeutic skills for legal assessments and dangerousness predictions, as well as true therapeutic engagement.
The inpatient environment  must be conducive to habilitation and 
rehabilitation. As well as treatment of speciﬁ  c disorders, the core

rehabilitation. As well as treatment of speciﬁ  c disorders, the core 
concern of staff is aiding independent living. A sense of progress, evident in both the physical environment and staff attitudes, encourages hope and consolidates treatment gains. This sense of progress can be achieved in several ways:
◆ provision of graded living spaces in which patients can experi-ence greater autonomy;
◆ increasing engagement in work, education and recreation;
◆ extending responsibility for personal and domestic care tasks;
◆ phased introduction of supervized activities outside the institu-tional boundaries, appropriate to the patient’s mental state and public safety;◆ consideration for and support of family and social relationships, and a basis for developing sustainable social networks. Intimate relationships constitute an important element of this aspect of the work.
(42)

(42)
Successful return to the community  depends on everyone having a 
sense of security. This will require suitable accommodation, basic ﬁ nancial provision and skills for managing ﬁ  nances, a sense of con-
trol over mental disorder, and sufﬁ  cient mastery of local services to 
be able to ﬁ  nd help in a crisis. Regular reviews of the service user, 
the services, their use of these services, and the goodness of ﬁ  t 
between them, are essential. People regarded as posing a special risk of harm to others may be referred to a multi-agency public protection panel (MAPPP , 
(43, 44) ; see also Chapter 11.16).
Direct involvement of the patient in setting goals for health and 
for safety creates in the patient a sense of ownership of resultant plans, and is likely to improve collaboration with them. The proc-ess of community re-entry is summarized in Fig. 11.17.2, drawing on  a grounded theory of discharge from a secure hospital.
(45) It

(45) It 
lends itself to the development of outcome measures which are more appropriate for an offender patient  than the almost exclu-
sively used but over-simplistic measure of re-offending. The core concern is movement between pathological dependence and healthy independence, with staff taking an active role in facilitating progress in two phases—paving the way, when skills necessary to the attainment of independence are built up, and testing out, when 11.17  management of offenders with mental disorder in specialist forensic mental health services
Self-management
and rehabilitation(Re)-establishing safety and
security
Further assessment and
specific treatmentsAssess disorders, needs, risks, deficits and strengths;
provide report for Court as necessary. 
Advice and support to primary caregiver / treater.
Admit to specialist unit; initiate symptomatic treatment;

reduce anxiety and distress; devise and implementcare plan to regulate diurnal cycle and contain self- andother-directed aggression or violence.
Identify cerebral dysfunction; identify relevant social
history and genetic factors; treat psychosis and otherdisorders; treat trauma related and attachment deficitissues; promote insight, motivation, self-regulation andproblem solving.
Reducing internal criminogenic factors (cognitions,
schema, empathy), and risk elevating factors e.g.substance misuse. 
Promote independence through paving the way and
testing out. Life skills, interpersonal skills, awareness,relapse prevention and remediation plan.One orboth mayoccur
Both
should
occur
Longer term treatment and care for people with
treatment resistant conditions
Fig. 11.17.1 Schematic representation of typical treatment and care pathway.

SECTION 11  forensic psychiatry 2020
indivi duals are given opportunities to prove themselves in situa-
tions of increasing trust. Re-offending is important, but as a barrier to gaining or sustaining independence rather than the sole outcome indicator.
Assessing outcomes
Most studies of people who have been discharged from specialist security hospitals have serious limitations, which partly arise from political pressure to focus on the non-clinical outcome of re-offe nding
and inadequate funding of the studies, which are costly and time-consuming. Results of existing studies are limited by:
1 Choice of outcome measures, which are almost solely re-
offending, with some reference to mortality and hospital re-admission.
2 Lack of information about the nature of treatment. At best, there 
is information about length of stay in the institution. Some effects may be inferred, for example the complex model for treat-ing personality disorder in Broadmoor Hospital in England,
(46)

(46)
but most studies simply treat secure hospitals or units as a ‘black box’ .
3 Social attitudes, substance use, policies/legislation, and pro-
vision of specialist services all change over time and between jurisdictions.Further information
Home Ofﬁ  ce (2003) MAPPA Guidance. www.probation.homeofﬁ  ce.gov.uk/
pdf/MAPPA per cent20guidance.pdf Accessed 10.07.2007.
Jamieson, L., Taylor, P . J., and Gibson, B. (2006). From pathological 
dependence to healthy independent living: an emergent grounded 
theory of facilitating independent living. The Grounded Theory Review 
6, 79–107. 
Royal College of Psychiatrists (2006) Psychiatrists and Multi-Agency Public 
Protection Arrangements. www.rcpsych.ac.uk/memebers/current_issues/publicprotection.aspx. Accessed 27.07.2007

 1. Taylor, P . J., Grounds, A., and Snowden, P . (1993). Forensic psychiatry 
in the National Health Service of England and Wales. In Forensic 
Psychiatry, Clinical, Legal and Ethical Issues  (eds. J. Gunn & P . J. Taylor), 
pp. 691–731. Butterworth Heinemann, Oxford.
 2. Home Ofﬁ  ce, Department of Health and Social Security (1975). 
(Butler) Report of the Committee on Mentally Abnormal Offenders .
HMSO, London. Cmnd 6244.
 3. www.dspdprogramme.gov.uk
 4. Francis, R., Higgins, J., Cassam, E., et al. (2006). Report of the 
independent inquiry into the care and treatment of Michael Stone.

independent inquiry into the care and treatment of Michael Stone. 
South East Coast Strategic Health Authority, Kent County Council, Kent Probation Area. www.kent.gov.uk/publications/council-anddemocracy/ michael-stone.htm Accessed 20.07.2007PRE-DISCHARGE POST-DISCHARGEPATHOLOGICAL
DEPENDENCE
InsitutionalizationHEALTHY
INDEPENDENCE
Community living &
free choice1
1 and 22Enhancers *
Continuous effect promoting independence
Barriers  *
Act to decrease chance of
attaining independenceTerminators of independence
e.g. re-offending* Individual differences and situational
factors can act as both enhancers andbarriers to independence
1
2Paving the way : acquiring skills (e.g. cooking, budgeting), education, raising self-esteem
Testing out : trial leave, conditional discharge, graded exposure to community living

1
Fig. 11.17.2 Attaining healthy independence while recovering from serious mental disorder and offending: A model.

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. (2004). Access to medium 
secure psychiatric care in England and Wales: a national survey of 
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London.11.17  management of offenders with mental disorder in specialist forensic mental health services

Index
AA (Alcoholics Anonymous) 451–2, 459, 
1279, 1352
AACD (age-associated cognitive decline) 1535
AAI (Adult Attachment Interview) 309–10
AAMI (age-associated memory 
impairment) 1534–5, 1535–6
Abbreviated Injury Scale 1105
ABC analysis 96, 413–14ABC medical assessment 1106
ABC transporters and complementary 
medicines 1249–50, 1250
Abel Screen 1962
Aberrant Behavior Checklist 94, 1823
ability, general, assessment of 87, 88
ablative neurosurgery see neurosurgery for 
mental disorder
abortion 1119, 1883
late 1119
self-induced 1117
Abraham, Karl 306
abridged somatization index 1000absolute risk reduction 128
abstinence
from alcohol 450
in psychoanalysis 1339
abulia 379acamprosate 454, 1246 , 1542
‘accident neurosis’ 1055
accidents 1105–13
classiﬁ  cation of physical injury 1105
compensation claims 1111–12epidemiology 1105
litigation following 1111–12
needs of signiﬁ  cant others 1108
and psychiatric disorder 1105
psychological trauma 1105–6
assessment at accident scene 1106–7

long-term assessment and 
treatment 1110–11
responses seen in emergency room 1107–8treatment during hospital stay 
1108–10, 1109
and sleep disturbance 926, 1108
acetylcholine 429
and the basal forebrain 150
identiﬁ  cation 168
and memory 253receptors 173, 206, 1171
role in neurodevelopment 159
in substance use disorders 429
acetylcholinesterase 155
aciclovir 1091
acné excorié  618, 917–18, 1044
acromegaly and hypersomnia 942
acrotomophilia 833
ACSeSS (Admission Criteria to Secure Services 
Schedule) 2018
ACT see assertive community treatment
ACTH 170
in depression 661
and insomnia 935
release in response to stress 1135tumours producing 1101
actigraphy 934, 1697
acting out 299, 300
Action Program T est 90
action-taking, legal aspects 1895–900Active Life Expectancy 1509–10
activities of daily living (ADL)
in Alzheimer’s disease 335

instrumental 337
in mild cognitive impairment 1535
activity scheduling in body dysmorphic 
disorder 1047
acute and transient psychotic disorders 602–8
acute intermittent porphyria 212
acute polymorphic disorder with symptoms of 
schizophrenia 605, 1124
acute polymorphic psychotic disorder without 
symptoms of schizophrenia 604–5
acute renal failure 1087
acute schizophrenia-like psychotic 
disorder 536, 603, 605
Acute Stress Disorder Interview 695
Acute Stress Disorder Scale 695
acute stress reactions 693–9
, 716
aetiology 696assessment 695
childhood and adolescence 1729
classiﬁ  cation 693, 694
clinical features 693–4
comorbidity 696course and prognosis 696–7
diagnosis 694–5, 694differential diagnosis 695
epidemiology 695–6
following an accident 1107, 1108in HIV/AIDS 1091
and offending 1923

predictors of 697
prevention 698
treatment and management 697–8victims of criminal activity 1984–5
ADsee Alzheimer’s disease
Adaptive Behaviour Scales 1821
ADARDS unit 1583
ADAS-Cog (Alzheimer’s Disease Assessment 
Scale-Cognition) 1240
addiction
‘primary addiction’ theory 434
role of personality 428–9
routes and risks of 430–1, 431
self-medication hypothesis 434
use of term 427
Addiction Severity Index 1164
Addison’s disease 1086
adenine 223adenosine receptors 173
adenylate cyclase 174, 176, 473, 1201
ADH see alcohol dehydrogenase; vasopressin
ADHD see attention-deﬁ  cit hyperactivity 
disorder
adjustment disorders 716–24 ,1066–9
acute 717
aetiology 720, 1067–8
and age 719, 721–3
associated features 719
childhood and adolescence 721–3
after diagnosis of physical illness 
1741, 1742

disorder
acute 717
1741, 1742
diagnostic criteria 1669–70, 1671
chronic 717
classiﬁ  cation 106, 1066–7
clinical features 720
comorbidity 719
course and prognosis 1068
deﬁ nitions 716–19, 716,717, 1066–7
and deliberate self-harm/suicide 718, 722diagnosis 1067, 1669–70, 1671
differential diagnosis 695, 1067, 1657elderly people 1552Note: Page numbers in bold  refer to main entries. Those in italic  refer to ﬁ  gures and / or tables. Alphabetical order is word-by-word.
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022adjustment disorders ( cont.)
epidemiology 719, 1067
postoperative 1099–100
stressors 718, 720
subtypes 717, 720
symptom proﬁ  le 717–18
in terminal illness 1069–70
treatment and management 720–3, 1068–9, 
1069 , 1278
ADL see activities of daily living
Admission Criteria to Secure Services 
Schedule 2018
ADMP 73
adolescence see childhood and adolescence
Adolescent Transitions Program 1790
adoption 1120
effects on child and adult mental 
health 1747–52
history-taking 1601
open 1747
total severance model 1747
adoption studies 216
anxiety disorders 1667attention-deﬁ  cit hyperactivity 
disorder 1646
conduct disorder 1659
in gene–environment interaction 217–18
mood disorders 651offending behaviour 1918
schizophrenia 548–9, 553–4
adrenaline 150
in conduct disorder 1658
functions 161
adrenergic receptors 1171
antidepressant actions at 1172, 1187
antipsychotic actions at 1209, 1211
and depression 1185, 1185

in generalized anxiety disorder 732and post-traumatic stress disorder 706
and suicidal behaviour 965
adrenocorticotropic hormone see ACTH
Adult Attachment Interview 309–10
Adult Memory and Information Processing 
Battery 88
advance directives 30, 1577, 1899
advanced glycosylation end products 1509
advanced sleep phase syndrome 1261, 1699
aetiology
contribution of epidemiology 280–9
contribution of genetics 212–22 ,222–33
contribution of social sciences 268–75 ,
275–9
Afa 1420
affective blunting in schizophrenia 529
affective psychosis and Prader Willi 
syndrome 1826
affects
Freudian theories of 295
and object-relations theory 302, 303
afﬁ liative traits 886, 888
Africa
attitudes to psychiatric disorder 6
psychiatric nurses in 1406–7
age-associated cognitive decline 1535

Africa
age-associated memory impairment 1534–5, 
1535–6
age of consent 1899–900
age of criminal responsibility 1945, 1954AGE products 1509ageing
as an energy crisis 1509
biology of 1507–11
and circadian rhythms 1572
and culture 1512–13
and dementia 1520dietary modiﬁ  cation 1509
disengagement theory of 1512
genomic theories 1507–8
and life expectancy 1507, 1509–10
and mitochondria 223
and modernization 1512
and narrative gerontology 1514–15
population 1579
and schizophrenia 544–5
and sexual function 1569, 1569
and sleep 925–6, 1571–2social constructionist approach 1515
sociology of 1512–16
stochastic theories 1508–9
successful 1512
and transitions 1513–14
see also  elderly people
aggression
adolescent see antisocial behaviour, 
adolescent
in antisocial personality disorder 866

biodevelopmental processes 889
and body dysmorphic disorder 1044
in conduct disorder 1656
in dementia 336, 1920–1, 1928–9as a diagnostic feature 1928–9
and epilepsy 1078, 1864, 1929, 1929–30
following an accident 1107, 1108, 1920following head injury 393, 396, 1929
and Huntington’s disease 1929
ictal 1930
impulsive/episodic 912
information-processing model 1658and intellectual disability 1855–6, 1929
neurobiological determinants 1917–18
passive 876
in physical illness 1132–3
severe maladaptive in childhood and 
adolescence 1798
and substance use disorders 1926
and suicide 970
and Wernicke–Korsakoff syndrome 1929
see also  violence
aggressive drive 294, 295, 302
agitation
in dementia 413–15
in elderly people 1527
following head injury 393, 396in physical illness 1132–3
postoperative 1098–9

agitation
in schizophrenia 529
agnosia in Alzheimer’s disease 334
agomelatine 671agonists 1171
agoraphobia 52, 750, 752
elderly people 1559
with panic disorder 740–1, 750–64
agranulocytosis, drug-induced 1223agraphia, pure 54
agreeableness 850, 886, 888
AIDS see HIV/AIDS
AIS (Abbreviated Injury Scale) 1105
akathisia 58,730, 1222
akinesia 58, 58Alanon 1352
alarm clock, dawn-simulating 1261
alcohol
abstinence vs. controlled drinking 450
addictiveness 431
advertising/promotion restrictions 470
age limits on drinking 469–70
as anxiolytic 1178
awareness of compulsion to drink 439
binge drinking 646control of availability and conditions of use 
469–70
drink-seeking behaviour 438drinking repertoire 438drug interactions 1175
education about 468
effects on sleep 1572‘expectancies’ 434
‘harmful use’ 440

469–70
integrated societal policy 471
intoxication 442–3
as a legal defence 1901
and offending 1926, 1927–8
legal prohibitions on 468
paradoxical reactions with 1180
‘pathological intoxication’ 442, 1926rationing sales 470
reinstatement of drinking after abstinence 439
relationship between consumption and 
violence 1926
sensitivity to 435taxes on 470
temperance movement 470
tolerance to 438
alcohol abuse, terminology 439–40
alcohol dehydrogenase 435
alcohol dependence syndrome 437–42
and classiﬁ  cation 439
clinical features 438, 438
elements of 438–9
validity of 438
alcohol-induced amnesia 404, 443
alcohol-induced dementia 182–3, 399–402 ,
444, 1541
alcohol-related brain damage 182–3, 399–402 ,
444, 1541
alcohol-related neurodevelopmental 
disorder 1615, 1841
alcohol-related problems 438, 440–1
Alcohol Stroop T est 265
alcohol use

444, 1541
444, 1541
assessment 442, 448
guidelines for safety 432
and health 1136
recommended intake for elderly people 1540
alcohol use disorders (AUDs)
and accidents 1110
aetiology 432–7
biopsychosocial model 433
genetic factors 434–6
psychological factors 433–4
sociocultural factors 433
and anxiety 427
assessment 448
instruments 1484, 1542
in childhood and adolescence 456, 464
as a chronic relapsing disorder 447–8
classiﬁ  cation 437
cognitive assessment 92comorbidity 427, 434, 443–4

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022benzodiazepine misuse 492
bipolar disorder 646
bulimia nervosa 804, 806
cyclothymia/cyclothymic disorder 687
depression 649panic disorder 455, 752services for 465sleep-wake disorders 931
treatment 455–6
and dopamine receptors 229
effects on family and carers 452–3, 465
elderly people 1519, 1540 ,1540–2 ,1541
and employment 456
ethnic minorities 464
family history positive 434, 434
global disease burden 10, 467
and head injury 393–4
in health care workers 457
and homelessness 456, 464informants 448
inpatient care 1453
and intoxication 442–3
and jealousy 620
late-onset 1540
legal issues 1927–8
levels of severity 1541
and liver transplantation 456
memory impairment in 404
mental health services 459–67
neuropathology 182–3, 183
parental, effects on child development 1754and personality 434
physical disorders associated 444–5
in pregnancy 1117, 1448, 1614–15, 1754, 
1826, 1841
prevalence 285
prevention 467–72 , 1448–9
deterrence 468

1826, 1841
education/persuasion 468
harm reduction strategies 469
providing/encouraging alternative 
activities 468–9
regulating availability and conditions 
of use 469–70
social, religious and community 
movements 470
preventive/prevention paradox 460, 467
in primary care, detection 1484
reasons for 427
relapse prevention 450–2, 450,451
spectrum of 459–60, 460
and suicide 427, 444, 955, 956
terminology 437
treatment 5521–33 , 428
Alcoholics Anonymous 451–2, 459, 
1279, 1352
brief interventions 460–1, 463
community-based 461–2
coping skills therapies 451
cost-effectiveness 462–3
counselling 1279cue exposure 451
deterrent medication 453–4, 1542
effectiveness 470–1
follow-up 457
inpatient 449, 455–6, 461matching of patients to 452, 455, 456, 462
motivational interviewing 451
pharmacotherapy 1246spectrum of 459–60, 460starting 448
stepped care 462

treatment gap 13
type I/type II 429
in women 454–5, 464
see also  alcohol dependence syndrome
Alcohol Use Disorders Identiﬁ  cation T est 
284, 460, 1542
alcohol withdrawal 443
alleviation by further drinking 439
complementary medicines 1249
explanation of symptoms 448
inpatient 449, 461
medical assistance 448–9, 449, 1542
outpatient 448, 461–2with perceptual disturbance 443psychosis in 58, 443, 449–50, 538with seizures 443, 449
symptoms 438–9
tachycardia in 448
and violence 1926
alcoholic blackouts 404, 443
alcoholic hallucinosis 443, 538
Alcoholics Anonymous 451–2, 459, 1279, 1352
alcoholism 437
see also  alcohol use disorders
aldehyde dehydrogenase (ALDH) 435
ALE (Active Life Expectancy) 1509–10alexia 54
alexithymia 850, 1005
algogenic psychosyndrome 851
ALI hierarchy 1372, 1372
alleles 212–13, 226

association studies 220–1, 220
allocortex 148, 149
allostatic load and ageing 1507
alogia 53
1-α-acetylmethadol hydrochloride 1243–4
α-calcium calmodulin-dependent kinase II 
(α -CaMKII) 889, 890
α-crystalin 362
α-melanocyte stimulating hormone 
(α -MSH) 170
α-secretase 338
alpha-synuclein protein/gene 362, 365, 369
α2-agonists in opioid detoxiﬁ  cation 477
alprazolam
antipanic actions 1180in cancer 1102
in delirium 1533
in panic disorder 756–7, 756
pharmacokinetics 1172 , 1179
potential for misuse 491
in social anxiety disorder 743
alternative medicine see complementary 
medicines
Alzheimer’s disease (AD) 333–43
aetiology and molecular neurobiology 337–9and ageing 1520
assessment 92, 265–6, 337, 1240
behavioural and psychological symptoms 413
biomarkers 341
carers 340classiﬁ  cation 336
clinical features 334–6

cognitive impairment in 334–5
delaying onset/disease modiﬁ  cation 341, 1538
and delirium 1532and depression 335diagnosis 336–7differential diagnosis 347, 364, 373, 380
and Down syndrome 1584, 1827, 1839, 
1865, 1880
early detection 265–6, 1519–20
epidemiology 1519–22
functional impairment in 335
genetic counselling 340
genetics 227, 339, 1521
history of disorder 334
history-taking 336–7
impact 1522
incidence and risk factors 1520–2, 1520 ,1522
Lewy body variant 362
and mild cognitive impairment 1534, 1534 ,
1535–6, 1538
neuroﬁ  brillary tangles 337–8, 339
neuropathology 337–9
amyloid cascade hypothesis 338
cholinergic hypothesis 338, 1240–1
presenilin genes 339
personality change in 335–6prevention 341
psychoses in 335
risk reduction/protective factors 1521–2, 
1522 , 1538
and sleep-wake disorders 931
sporadic/familial 339

1522 , 1538
translational research 341treatment and management 339–41, 1240–1
Alzheimer’s Disease Assessment Scale-
Cognition 1240
amantadine 374, 1226, 1876
ambitendency 58aMCI (amnestic mild cognitive impairment) 
1520, 1535
amenorrhoea in anorexia nervosa 782, 783, 787
AMHPs (approved mental health 
practitioners) 1410
amimia 346
amines 168
amino acids 168
amisulpride 1209
administration 1220adverse effects 1212
pharmacodynamics 1210
pharmacokinetics 1222
amitriptyline 670
adverse effects 1191
in anxiety disorders 1182
in cancer 1103
dosage 1196
drug interactions 1175, 1233
in personality disorders 905
pharmacodynamics 1173 ,1187
pharmacokinetics 1172 ,1189
amnesia 59
alcohol-induced 404, 443
in Alzheimer’s disease 334anterograde 59, 92, 252, 391
assessment of awareness of 420–1

amnesia 59
assessment of functional consequences 420
assessment of memory 89, 89, 253, 254, 
255–6, 264, 420–1, 420
in brain tumour 1075
and cerebrovascular disease 407for criminal offences 405, 1927
in dementia 59
dissociative 714, 715, 1012
following ECT 404, 1257
following hypoxia 406–7

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022amnesia ( cont.)
in fugue states 404–5
global 59
in herpes encephalitis 406
malingered 1055–6memory remediation and rehabilitation 
421–4, 422
partial 59
persistent 405–8
post-traumatic 388, 390–1, 404, 407
in post-traumatic stress disorder 404, 714
psychogenic 59
psychogenic focal retrograde 405retrograde 59, 252, 408
following head injury 388, 388, 391
selective 57
transient 403–5
transient epileptic 403
transient global 59, 403
use of memory aids and strategies 420, 421
in vascular dementia 379
in Wernicke–Korsakoff syndrome 92, 405–6see also  memory impairment
amnesic syndromes 403–11
associated with alcohol use 1541
elderly people 1531
amnestic mild cognitive impairment 1520, 1535amok  606, 979, 981
amotivational syndrome, cannabis-
associated 508
amoxapine 669
adverse effects 1190, 1191
pharmacodynamics 1187
pharmacokinetics 1189
AMPA receptors 172, 173, 174, 1171
AMPAkines 174amphetamine 482–6
addictiveness 431, 483

in attention-deﬁ  cit hyperactivity disorder 
1241, 1876
effects of 483, 483
in intellectual disability 1876
misuse
aetiology 484
complications associated 484–5
course and prognosis 484–5diagnosis 483–4
epidemiology 484
prevention 485
treatment and management 485
pharmacodynamics 1172preparations 482–3
psychosis due to 485
withdrawal 483, 483
amphotericin B 1091
ampicillin 1532amygdala 152, 152–3, 158, 201
and associative learning 258
and emotion 258, 259, 264
and fear/anxiety 1666, 1667 , 1668
in generalized anxiety disorder 732–3and memory 251, 253, 259, 264
and orbitofrontal cortical development 1919
amygdalotomy 1267
amylase serum levels in bulimia nervosa 804
amyloid 338amyloid precursor protein 338
anabolic steroid abuse 1045
anaclitic type 316anaemia 785, 1087–8

anaesthesia, glove and stocking 57
anaesthetics, adverse effects 730
anal phase of development 294, 295analgesics
combination formulations 1169
in somatization disorder 1009
suicide risk 973
analysis of variance 138analytical behaviourism 133–4
analytical functionalism 134–5
anandamide 172, 429, 429
, 507
anankastic personality disorder see obsessive–
compulsive disorder
anankastic phenomena 52
androgen therapy in gender identity 
disorder 843
androgens 815–16, 816, 826
androstenedione 815
anencephaly 156
aneuploidy 228
aneusomy 228
angel dust see phencyclidine
behavioural and psychiatric aspects 1841–2
and epilepsy 1864, 1865
genetics 213, 224, 229, 1841, 1865, 1866
physical characteristics 1841
prevalence 1841
Anger Coping and Coping Power 
Programme 1662, 1782
anger management

in adjustment disorders 1069
in antisocial personality disorder 898in anxiety disorders 1295–6
in conduct disorder 1662, 1782
in intellectual disability 1874
aniracetam 1240
Anna O 1338anomia 253, 850, 1449
anorexia nervosa 777–800
and adverse life events 779–80
aetiology 778–82
biomedical factors 781–2family factors 780
multidimensional approach 778–9, 779
sociocultural factors 779
age at onset 778
assessment instruments 777and body image 57
and child sexual abuse 780
childhood and adolescence 1784
classical post-pubertal 782–6
classiﬁ  cation and diagnosis 787–8, 800–1, 801
course and prognosis 788–9
as culture-bound syndrome 779
and depression 783, 787
differential diagnosis 784, 787
early onset/premenarchal 786–7, 788–9epidemiology 777–8
ethical issues 796
and gender 778
genetics 781–2, 806

history of concept 777hypothalamic model 781
incidence 778
maintenance 1299
in males 788
malnutrition in 784–6medico-legal issues 796mortality 788–9
myopathy in 785
and obsessive–compulsive disorder 783
osteoporosis in 785
overlap with bulimia nervosa 800, 801
and parenthood 786
and personality disorders 780–1, 884
and postnatal depression 780
and pregnancy 780, 784, 1118
prevalence 778
prevention 796–7
psychopathology 779, 783, 786–7
relationship with other eating disorders 804
risk factors 806
and socio-economic status 778
and suicide 955
temperature regulation in 785
treatment 789–96
antidepressants 795, 1193
cognitive-behaviour therapy 792, 796, 
1298–303
compliance 794
complications 786compulsory 793, 795
day care/community 793, 795
dietary care 794–5
dynamic psychotherapy 796

1298–303
eating disorder units 792–3
family therapy 790–2, 790, 796
inpatient 792–3, 793, 794–5
interpersonal psychotherapy 792
nursing 794–5
ANOV A 138
Antabuse® 453,
730,1246 , 1542
antagonists 1171–2
anterior capsulotomy 1267, 1269 , Plate 15
anterior cingulate cortex 245
anterior cingulotomy 1267, 1270 , Plate 16
anterior commissure 151, 157anthropology see social and cultural 
anthropology
anthropophobia 982
anti-androgens in the paraphilias 838
anticholinergics
adverse effects 365, 487, 1225
anxiety 730
delirium 331, 1532
memory loss 404
parasomnias 946
in management of antipsychotic adverse 
effects 1225
anticipation 213, 228, 652
antidepressants 669–71, 670,1185–98
in adjustment disorders 721, 1068administration and dosage 1195, 1196
adverse effects 674, 1190–3, 1191 ,1192

cardiotoxicity 1794–5
epileptogenicity 1078sexual dysfunction 826–7
suicide risk 971, 973, 1192, 1668, 1707–8, 
1796, 1923
in alcohol use disorders 455
in anorexia nervosa 795, 1193–4
in anxiety disorders 1182, 1193
and attempted suicide 670, 674
in attempted suicide 970–1, 1192
in bipolar disorder 671–2
in bulimia nervosa 807–8, 809, 1193–4
in cancer 1102, 1103

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022in childhood and adolescence 674–5, 1676, 
1794–5, 1796
choice of 674
classes of 1186–8, 1187
complementary medicines 1248
contraindications 1194
delayed onset of effects 176, 176
in dementia 416
dosage 674–5
drug interactions 1194–5, 1195
in dysthymia/dysthymic disorder 684–5
in elderly people 674, 1554–5, 1554
in generalized anxiety disorder 735history of 1185–6, 1185
in HIV/AIDS 386, 1092
indications 674, 1193–4, 1193
in intellectual disability 1875–6
in obsessive–compulsive disorder 768–9, 
770, 1193, 1687–8, 1687
overdose 1192in persistent somatoform pain 
disorder 1033–4
in personality disorders 905, 906
pharmacodynamics 1172–3, 1173 ,
1186–8, 1187
pharmacokinetics 1172 , 1188–9, 1189
in post-traumatic stress disorder 709precautions with 1796
in pregnancy 675, 677, 761–2, 1117, 1192
prescription in physical illness 674, 1132
and surgery 1097–8
switching between 674in terminal illness 1070
theories regarding actions of 1185–6, 1185

withdrawal 1195
see also speciﬁ  c drugs and types of drugs
antiemetics
adverse effects 1101
in chemotherapy 1101
antiepileptic drugs 1231–40
adverse effects
behavioural disorders 1867–8
on cognitive function 92
teratogenicity 1169
in bipolar disorder 671, 672, 1556in childhood and adolescence 1798
with psychiatric/behaviour disorder and 
intellectual disability 1852
choice of 1866–7
drug interactions 1866
in elderly people 1556
in epilepsy 1080
with intellectual disability 1866–7, 1867
in intellectual disability 1852, 1866–7, 
1867 , 1876
in Landau–Kleffner syndrome 1627
pharmacokinetics 1867
structures 1232
withdrawal 1867
see also speciﬁ  c drugs
antihistamines

1867 , 1876
antihypertensives, adverse effects 827
antilibidinal drugs in intellectual 
disability 1876antilibidinal object 308
antioxidants
and longevity 1509in tardive dyskinesia 1249
anti-PrP antibodies 359anti-psychiatrist movement 28
antipsychotics 1208–31
in acute and transient psychotic 
disorders 606
administration 1213–22, 1214
adverse effects 58–9, 1212 , 1222–5
acute sensitivity reactions in dementia 
with Lewy bodies 361–2, 365
akathisia 730, 1222
anxiety 1101
in childhood and adolescence 1677, 1797–8cognitive impairment 580
diabetes 1085
dystonia 1222
in elderly people 1548
epileptogenicity 1078, 1223
hyperprolactinaemia 1086, 1217, 1223
hypersomnia 939hypotension 1223, 1529
management 1225
‘neuroleptic toxicity’ 588

parkinsonism 580, 1222–3
sexual dysfunction 827tardive dyskinesia 1223
see also  neuroleptic malignant syndrome
in alcohol withdrawal 449–50
antidepressant actions 581
in anxiety disorders 1182in attempted suicide 971
in attention-deﬁ  cit hyperactivity 
disorder 1652
atypical 1172, 1209, 1209
in autism and other pervasive developmental 
disorders 1640
in bipolar disorder 677
in cancer 1104
in childhood and adolescence 
1677, 1796–8, 1852
classiﬁ  cation 1209–10, 1209
in delirium 331in dementia 414–15
in dementia with Lewy bodies 367
depot formulations 581–2
drug interactions 1221–2
high-potency 1209in HIV/AIDS 386, 1092
in Huntington’s disease 374
indications and contraindications 1225
in intellectual disability 1875
low-potency 1209mid-potency 1209

in personality disorders 600, 905, 906
PET/SPET imaging studies 189–90
pharmacodynamics 1172, 1210, 1211 ,
1212–13, 1212
pharmacokinetics 1172 , 1221–2
polypharmacy 587–8
in pregnancy 677, 1118
resistance to 582, 590, 1213
risk: beneﬁ  t appraisal 585, 586
in schizoaffective disorder 598
in schizophrenia 579–82, 579, 585, 586–8, 
586, 1213, 1215 , 1548
and surgery 1098in tic disorders 1073, 1688
typical (ﬁ  rst generation) 1209, 1209
antisocial behaviour, adolescent 1654, 1945–59
assessment 1947–8, 1949
and attention-deﬁ  cit hyperactivity disorder 
1948–9
and autism spectrum disorders 1950
and capacity 1954–5
and conduct disorder 1946, 1948–9
and depression 1949
and early-onset psychosis 1950epidemiology 1945
girls 1955–6
interventions 1950–7, 1951
justice system 1945, 1947

legal issues 1954–5and mental disorder 1946–7, 1948–50, 1951–2
pathways of care 1947pathways to 1946
and post-traumatic stress disorder 1949–50
protective factors 1947, 1947
risk factors 1946 , 1947
antisocial behaviour, adult see offending
antisocial personality disorder 865–6
aetiology 866classiﬁ  cation 851, 856,865
clinical features 866
comorbidity 866
course and prognosis 866
and deception 1049diagnosis 866
differential diagnosis 866, 1657
in elderly people 1561, 1562 , 1563
epidemiology 865, 882, 883
following head injury 391and genetic–environmental interactions 315
offenders 1921
prisoners 1933
relationship with attention-deﬁ  cit 
hyperactivity disorder 1931
terminology 856
treatment 866, 898, 898–9, 904
anxiety
as an alarm signal 295
anticipatory 751and arousal 55

anxiety
assessment instruments 1164
in bulimia nervosa 803
in cancer 1101–2, 1101
in childhood and adolescence
assessment 1665
with intellectual disability 1851–2with physical illness 1742–3
and conversion disorder 1014–15, 1015counselling in 1278
deﬁ nition 1664
in depression 634‘depressive’ 307
and diabetes mellitus 1085
drug-induced symptoms resembling 730
elderly people 1558–61
and epilepsy 1080following an accident 1106, 1108–9
and functional symptoms 993
and hyperthyroidism 1085
malignant 983
pathophysiology 1666–8, 1667
in physical illness 1131–2, 1742–3
in pregnancy 1117preoperative 1097

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022anxiety ( cont.)
and sexuality 825
in T ourette syndrome 1073
trait 1137
and ventricular dysrhythmias 1081
acute-on-chronic 1180
alcohol-induced 427, 434, 444, 455
assessment 1289, 1289
with attention-deﬁ  cit hyperactivity 
disorder 1650
and bipolar disorder 646
childhood and adolescence 1664–9
clinical course and outcome 1666
clinical presentation 1665–6comorbidity 1666, 1673
differential diagnosis 1671
epidemiology 1665–6
treatment 1668, 1779–80
chronic 1180
and chronic fatigue syndrome 1037
classiﬁ  cation 105
cognitive content 1286–7
cognitive model of 1289–90, 1290
and depression 649
elderly people 1531, 1579following head injury 393
following stroke 1071–2
genetics 1667
and hypochondriasis 997, 1024, 1027
and intellectual disability 1855and kleptomania 1943
and pain 1030
parental, effects on child development 1754

and persistent somatoform pain 
disorder 997, 1032
postpartum 1121–2
and somatization disorders 996
and stress 1667–8and suicide 955
treatment
antidepressants 1182, 1193
cognitive-behaviour therapy 1285–98 ,
1668, 1779–80
interpersonal psychotherapy 1324
neurosurgery 1267
see also  anxiolytics
vulnerability to 732, 734–5see also  generalized anxiety disorder
anxiety management
in depression in elderly people 1555
in obsessive–compulsive disorder 1685
‘anxiety neurosis’/‘anxiety state’ 729anxiety programme 1285
anxiolytics 1178–9
in cancer 1101–2, 1102
clinical effects 1179–81
complementary medicines as 1248
intravenous, in conversion disorder 1019
in obsessive–compulsive disorder 769
in pregnancy 1117
withdrawal from 730

anxious personality disorder see avoidant 
personality disorderAO (assertive outreach) teams 
1455, 1457–8, 1457
apathy
in dementia 416following an accident 1106
following head injury 391, 392, 396
following neurosurgery for mental 
disorder 1269
aphasia 53
acquired childhood 1712
acquired epileptic 1626–7, 1639, 1864in Alzheimer’s disease 334
assessment 89
jargon 54
progressive non-ﬂ
 uent 344
aphonia 53
Aplysia  315
APOE  gene/apoE protein and Alzheimer’s 
disease 339, 1521
apotemnophilia 833
APP  gene/APP protein 338, 339
applied tension in speciﬁ  c phobia 746
appraisal delay 1137
approved mental health practitioners 1410
‘approximate answers’ 54, 1055
apraxia in Alzheimer’s disease 334
archicortex 158Arctic hysteria 983
Argentina, attitudes to psychiatric disorder 6

aripiprazole 1209, 1209
administration 1214 , 1219–20
adverse effects 1212 , 1225
in bipolar disorder in elderly people 1556
in childhood and adolescence 1797
pharmacodynamics 1210, 1211
pharmacokinetics 1222pharmacology 1210
Aristotle 133
arithmetical skills, speciﬁ  c disorders of 1629–30
ARND (alcohol-related neurodevelopmental 
disorder) 1615, 1841
aromatherapy in dementia 414
arousal and anxiety 55
array CGH 1831
arson 1924, 1965–9
by children/adolescents 1954characteristics of ﬁ  re-raisers 1966
classiﬁ  cation 1966, 1966
historical context 1965
legal aspects 1966
management 1967–8motivation 1966 , 1967
prevalence 1965–6, 1965
art therapy 1352, 1413–17
with children 1414
contextual issues 1415–16
deﬁ nitions 1413

with elderly people 1415historical development 1414
with offenders 1415
people with intellectual disability 1414–15
in physical illness 1415
in psychotic illness 1415research 1416
in selective mutism 1714
artefactual illness 57
articulatory suppression in insomnia 
936–7
artiﬁ cial insemination 1114–15ascending reticular activating system in 
Alzheimer’s disease 1240
ascertainment
in family studies 215
in twin studies 216
aschemazia 57
asenapine 1209, 1210, 1220–1
aspartylglucosaminuria 1865Asperger’s syndrome 1638–9
aetiology 1639clinical features 1638
course 1639
deﬁ nition 1638, 1638
demographics 1639
differential diagnosis 865
epidemiology 1639
and juvenile delinquency 1950
management 1640
and offending 1921
prognosis 1639
asphyxiophilia 832, 833
aspirin, drug interactions 1232

assertive community treatment (ACT) 1402
in alcohol use disorders 462
in schizophrenia 584
assertive outreach teams 1455, 1457–8, 1457
acute stress reactions 695
adolescent antisocial behaviour 
1947–8, 1949
alcohol use 442, 448
alcohol use disorders 448Alzheimer’s disease 92, 265–6, 337, 1240
anxiety, in childhood and adolescence 1665
anxiety disorders 1289, 1289 , 1665
attention 60, 88–9, 264–5
attention-deﬁ  cit hyperactivity disorder 1645, 
1782–3
behavioural methods 94, 96–7, 96
benzodiazepine misuse/dependence 492
bereavement 726–7
bulimia nervosa 807by community mental health teams 1455
and categories of information 63
character 80–1, 80, 82–3
in childhood and adolescence 90, 1600–6
content of the clinical interview 
1600–1, 1602
developmentally sensitive

developmentally sensitive 
techniques 1601, 1604–5
laboratory tests 1605–6, 1605
mood disorders 1675need for multiple informants 1600
structure of the clinical interview 1601, 
1603–4, 1603
concentration 60, 88–9
and concepts of disablement 65and the concepts of disease, illness and 
sickness 63–4
concepts underlying procedures 63–7
condensation and recording of 
information 73–4
conduct disorder 1657, 1781–2
and conﬁ  dentiality 67
in consultation-liaison psychiatry 1146
contextual inﬂ  uences 67
and culture 67
depression 660
and diagnoses 74and the diagnostic process 64–5

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022distinction between form and content of 
symptoms 63
elderly people 1524–9
after treatment 1528–9
history-taking 1526
mental state examination 1526–7, 1528
physical 1527–9setting for 1525–7
formulation 73–4from complaint to formulation 66, 66
general ability 87, 88
instruments see assessment instruments
intellectual disability 1821–3
intelligence 22, 54, 87, 88, 263–4
and life events 66–7
mania 1675
memory 89, 89, 253, 254, 255–6, 264, 
420–1, 420
mental health services 1463–72
mild cognitive impairment 1536
as a multi-disciplinary activity 62, 68
obsessive–compulsive disorder 1783
offenders with mental disorder 2011–12, 2018personality 72–3, 78–85 , 286, 1164–5
personality disorders 858–9, 858
principles in general psychiatry 62–78
privacy of interviewing 67
and prognosis 74and psychodynamics 67
psychometric 85–7
psychophysiological methods 97
refugees 1496–7
and reviews 74sequence of 66
sleep-wake disorders 929–30

in childhood and adolescence 1696–7, 1696
somatization disorder 1005–6, 1005
summary 73–4temperament 79–80, 80
urgent 68
use of interpreters 67
and written reports 74–6
see also  cognitive assessment; needs, 
assessment; neuropsychological 
Assessment and Reduction of Psychiatric 
Disability 572
assessment instruments 69–73
administration 95–6
alcohol use disorders 1484, 1542
anorexia nervosa 777
anxiety 1164behavioural 94, 96–7, 96
behavioural and psychological symptoms in 
dementia 413
‘bottom-up’ organization 71
in childhood and adolescence 1591
with intellectual disability 1860
cognitive and neuropsychological 
functioning 87–9, 88,89,90, 263–7
comprehensive 73
computer-based 70, 263content and format 95, 95
contents of a good test manual 87
and context 268

creation 96
delirium 328
depression 69, 70, 1163–4, 1306, 1484, 
1551, 1552developments since the 1950s 70–2
disablement 284
in epidemiology 284–6
evaluation criteria 95
in evaluation of psychotherapy 1163–5of functioning 1165
information regarding 89
investigator-based 269
mental state and behaviour 69–70
multiaxial descriptive systems 73
multiple measures 96
needs 73, 94, 1433–4
in needs assessment 73, 1433
for negative symptoms 72
numeric analogue scales 1032
for personality 72–3, 81–2, 81
post-traumatic stress disorder 703
psychometric adequacy 95
psychopathology 1164
psychoses 1164
purpose of 94
quality of life 73, 1165
for quantiﬁ  cation of clinical outcome 73
questionnaires 94–8
rating scales 94–8
reasons for development of structured

reasons for development of structured 
interviewing and rating scales 69
response coding 97
for risk 1994, 1996–7screening 69
self-esteem 1164
sensitivity and speciﬁ  city 140–1, 284
service utilization 1165
standard vs. individualized 97standardized interview schedules 14, 284
substance use disorders 1164
‘top-down’ organization 71understanding and choice of 89–90
usefulness 1595
validity 140–1, 284
verbal descriptor scales 1033
visual analogue scales 1032see also speciﬁ  c instruments
assisted reproduction 1114–15
association therapy 836–7
associative learning 258, 696
asthma 1082
brittle 1050
and sleep-wake disorders 932
astroglia 157
astrology 1420
Asylum Act 1828 19
asylums 17–18, 18–19, 22, 24
ataques de nervios  983–4
ataxia
cerebellar, in alcohol use disorders 445
in HIV-associated dementia 384

ataxia
atmosphere, delusional 51atomoxetine 1688, 1795–6
adverse effects 1795
1241, 1648, 1650
and epilepsy 1650
precautions with 1795
suicidal risk 1796
ATP (Adolescent Transitions Program) 1790
ATP receptors 173
attachment theory 242–3, 242, 285, 
309–10 , 1725and child abuse 1735
and child neglect 1736
and conduct disorder 1659
and generalized anxiety disorder 734
internal working model (IWM) 243
and mentalization 1948mother–infant 1123–4and neuropeptides 888
and offending 1910
prenatal 1116–17
and psychopathology 243
secure/insecure attachment 242, 242,
309–10, 1725
and separation 1758
and stalking 1972
and transference 1342–3
attention 245–9
assessment 60, 88–9, 264–5
disorder 1643
brain regions involved 246
deﬁ cit 60

deﬁ cit 60
and delirium 325, 326
and depression 92
disorders of 60
divided 247–8
effects of disturbed sleep 926
and emotion 259
executive control 248–9, 248
following head injury 390
phasic 247
selective 60, 245–7, 264, 1288
shared 60
in somatization disorder 1005sustained 247, 264
vigilant 59, 247, 264
attention-deﬁ  cit hyperactivity disorder 
(ADHD) 60, 1613, 1643–54
in adult life 1647–8, 1652aetiology 1646–7
assessment 1645, 1782–3
classiﬁ  cation 1643
clinical features 1643
comorbidity 427, 646, 1073, 1644, 1650, 
1673, 1682, 1931
course and prognosis 1647–8
diagnosis 1643–5, 1849
differential diagnosis 1644–5, 1657, 1671
epidemiology 1645–6and gender 1646, 1828
genetics 1590, 1646
hyperactive/impulsive subtype 266
and intellectual disability 1850–1, 1876

and juvenile delinquency 1948–9legitimacy of diagnosis 28
neuropsychological assessment 266
and offending 1931pathogenesis 1647
prisoners 1931
refractory 1651–2
relationship with antisocial personality 
disorder 1931
and sleep-wake disorders 927, 931, 1695, 1697
and speech and language disorder/
difﬁ culty 1714
and stigma 1651
treatment and management 1241–2, 
1648–52, 1782–3, 1876
attentional blink paradigm 247attributional style 653

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022atypical schizophrenic disorder 866
AUDIT (Alcohol Use Disorders Identiﬁ  cation 
T est) 284, 460, 1542
audit of consultation-liaison psychiatric 
services 1147
AUDs see alcohol use disorders
aura 60, 1077
Australia, neurasthenia as diagnostic entity 1061
autism 1633–6
aetiology 227, 1635–6
atypical 1639
classiﬁ  cation 1623
clinical features 1633
comorbidity 1852
course 1635
deﬁ nition 1633–4, 1634
demographics 1634–5
differential diagnosis 865, 1639, 1644–5, 1657
and Down syndrome 1839
epidemiology 1634–5
and epilepsy 1852
and fragile-X syndrome 1635
and gender 1828genetics 1635–6
and intellectual disability 1852, 1855
and parental psychiatric disorder 1885prevention 1640
prognosis 1635
and sleep disorder 1697
and speciﬁ  c language impairment 1713
treatment and management 1639–40, 1875and tuberous sclerosis 1075, 1635
Autobiographical Memory Interview 89
autoerotic asphyxia 1703

autogynephiles 844
automatic behaviour in sleep-wake 
disorders 926, 928, 940, 945
legal issues 948–9
automatic obedience 58
automatic thoughts see negative automatic 
thoughts
Automatic Thoughts Questionnaire 1165
automatism
and epilepsy 403, 1077
‘insane’ 405, 1901
‘sane’ 405violent 1930
autonomic failure with syncope and orthostatic 
hypotension 361
autonomy, legal aspects 1895–900
autoprosopagnosia in Alzheimer’s disease 334
autoscopy 56
autosomal dominant disorders 212, 1831autosomal recessive disorders 212, 1831
Avena sativa 1248
avoidance 1287–8
in chronic fatigue syndrome 1039
following an accident 1107
and hypothalamic–pituitary–adrenal axis 658
in obsessive–compulsive disorder 768
and pain-related fears 1033in panic disorder 751
and phobias 745
avoidant personality disorder 872–3

aetiology 872
classiﬁ  cation 856, 872, 872
clinical features 872course 872differential diagnosis 862, 863, 865, 873
in elderly people 1562, 1562
epidemiology 872, 882, 883
and social anxiety disorder 740, 897
treatment 873, 897, 898
A VON Mental Health Measure 1434awareness of activity, disorder of 56
awareness of singleness, disorder of 56
ayahuasca 488, 501
azapirones 735
azoospermia 1114
azotaemia 1087
Babinski reﬂ  ex 158
Baby X experiments 1719
BAC (blood alcohol concentration) 442, 448
bah-tsche  983
Bali, attitudes to psychiatric disorder 7
Balint, Michael 308–9, 313
Banisteriopsis  (ayahuasca) 488, 501
barbiturates 1178
duration of action 1178
history of 1178
basal ganglia 154–5, 154
in alcohol use disorders 183

and memory 254in obsessive–compulsive disorder 1684
in schizophrenia 178
in tic disorders 1684
basic assumption theory 1353, 1356
‘battered child syndrome’ 1734–5Bayley Developmental Scale 1821
BDD see body dysmorphic disorder
BDI (Beck Depression Inventory) 719, 1163–4, 
1306, 1486, 1675
BDNF (brain-derived neurotrophic factor) 160,
171, 225, 652, 966, 1199, 1201, 1674, 1684
BDQ (Brief Disability Questionnaire) 284
‘BDSM’ sexual activities 832–3BDT (brief dynamic therapy) 720
‘Beating the Blues’ 1485
Bech-Rafaelsen Mania Scale 1164
Beck, A.T. 1304
Beck Anxiety Inventory 1164Beck Depression Inventory 719, 1163–4, 1306, 
1486, 1675
Beck Self-Concept T est 1164
Bedford College Life Events and Difﬁ  culties 
Schedule 1065
Beers, Clifford 22
behaviour
assessment instruments 69–70

1486, 1675
behaviour
and the unconscious 313
behaviour modiﬁ  cation
in attention-deﬁ  cit hyperactivity disorder 1649
in children and adolescents with psychiatric/
behaviour disorder and intellectual 
disability 1852
behaviour therapy
in agitation and challenging behaviour in 
dementia 413–14
attention-deﬁ  cit hyperactivity disorder 1648
in children and adolescents with intellectual 
disability and psychiatric/behavioural 
disorder 1852depression 15
history of 23nicotine dependence 512
obsessive–compulsive disorder 770
panic disorder 758
with sex offenders 1963
trichotillomania 915
see also  cognitive-behaviour therapy; 
exposure
behavioural activation in depression in elderly 
people 1555
dementia 412–17, 413,414

exposure
Behavioural Assessment of the Dysexecutive 
Syndrome 93
behavioural experiments in anxiety 
disorders 1294 , 1295
behavioural factors inﬂ  uencing health 1135–7
behavioural inhibition 1667
and generalized anxiety disorder 733, 733
and panic disorder 754, 762
Behavioural Pathology in Alzheimer’s 
Disease 413
behavioural phenotypes 1592, 1838, 1850, 
1851 , 1858
foetal alcohol syndrome 1614–15
neurogenetic syndromes 1613–14
behavioural programmes in intellectual 
disability 1874
behaviourally-induced insufﬁ  cient sleep 
syndrome 939
behaviourism 133–4
and personality 849
Benedict, Ruth 276
beneﬁ  t-ﬁ nding 1066
beneﬁ  ts,measurement of 1475
benzhexol 1532
benzodiazepine receptor agonists (BzRAs) 934
in insomnia 935
partial 1181–2
benzodiazepine receptors 1171, 1179

in generalized anxiety disorder 733, 734
benzodiazepines
in acute and transient psychotic disorders 607
adverse effects 934, 939, 1180, 1183
in alcohol withdrawal 449, 449, 1542
antiepileptic properties 1080, 1231
as anxiolytics 1178, 1179–80
in bipolar disorder 677in breastfeeding 1121, 1180
in cancer 1101–2, 1102 ,1104
cross-tolerance 491
in delirium 331, 1533
in dementia 415development 1178
effects on memory 409, 1179
in generalized anxiety disorder 735
as hypnotics 1179, 1182–3indications 1179–80
in insomnia 934
long-term use 1179
effects 1226
management of withdrawal 1181, 1181
misuse/dependence 490–3 , 1182
with alcohol dependence 492
assessment 492
by injection 491

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022cross-dependence 491
dependence at therapeutic doses 491, 
1180–1, 1183
and drug formulation 430
elderly people 1543
epidemiology 490–1
management 491–2
with opiate abuse 492–3
patterns of use 490–1
potential for 491
overdose 1180
pharmacodynamics 1171
pharmacokinetics 1172 , 1178–9
pharmacology 1179in postoperative delirium 1099
in post-traumatic stress disorder 710
in pregnancy 762, 1117, 1180
preoperative 1097
prescriptions 492
in schizophrenia 591–2
in social anxiety disorder 743, 744in speciﬁ  c phobia 746
in status epilepticus 1867
in terminal illness 1070
tolerance to 1179, 1180–1
benztropine 1225bereavement 724–8
after infant loss 725, 1120
assessment 726–7
in childhood and adolescence 235, 1758–60
and depression 725factors affecting course and outcome 725–6
in intellectual disability 1881
management 726–7
neurobiology 725
phenomenology of ‘normal grief’ 725physical and mental health consequences 726

violent traumatic 1985
see also  grief
Bergmann glia 158
beri-beri in anorexia nervosa 785β-adrenergic stimulants 730
β-amyloid protein
in Alzheimer’s disease 338
in dementia with Lewy bodies 362
in mild cognitive impairment 1537
β-arrestins 175
β-blockers
adverse effects 827
in speciﬁ  c phobia 746
β-crystalin 362
β-endorphin 170, 171
β-secretase 338
Better Services for the Mentally Ill  24
biastophilia 833
bifeprunox 1209
bilateral frontal lobotomy 1267
Binet–Simon scale 22
binge eating disorder 800, 801, 1299
Binswanger’s disease 377bioavailability 1170biofeedback in persistent somatoform pain

Binswanger’s disease 377bioavailability 1170biofeedback in persistent somatoform pain 
disorder 1034
biomarkers in Alzheimer’s disease 341Bion, Wilfred 308, 1353, 1355
biopsychosocial model 64, 207, 208,433,
990, 991
biperiden 1225
age of onset 665
anticipation in 652
biphasic episodes 665
aetiology 1674
assessment and monitoring 1675
course 1673–4
diagnostic criteria 1671, 1672
differential diagnosis 1645, 1657, 1671–3environmental risk factors 1675
epidemiology 1673–4
neurocognitive factors 1675
treatment and prevention 1676–7
classiﬁ  cation 639–40, 643, 643
comorbidity 645, 646
course 665–6and cyclothymia/cyclothymic disorder 688
deﬁ nition of bipolar 638
diagnosis 645–6
differential diagnosis 866, 868, 871
duration of episodes 665elderly people 1556–7
epidemiology 645–7, 650–1
genetics 650–8
global disease burden 645

history of concept 631hyperthymic 638
and intellectual disability 1827, 1854–5
late-onset 665
mixed states 636, 638
mortality associated 666outcome 666
overlap with other disorders 645
overlap with schizophrenia for 
susceptibility 652
patient state ﬂ  uctuations within 632–3, 
632,633
pharmacogenetics 653
in pregnancy 677
prevalence 646
prisoners 1934
psychosocial factors 653
psychotic 665
rapid cycling 636, 668, 677
recurrence 665–6
risk factors 646, 1675social functioning in 653
subtypes 631, 638, 643, 665
and suicide 1704
and surgery 1098
treatment
acute 671
continuation 677
and course 667
electroconvulsive therapy 1253–4
interpersonal and social rhythm 
therapy 1323
long-term 678
maintenance 671–2, 677
management of 677–8
neurosurgery 1268psychotherapy 673treatment gap 13

and use of mental health services 646
bipolar spectrum 680
birth certiﬁ  cate, change of sex on 845
birth season and schizophrenia 547, 556
birth weight
and HPA function 659
and schizophrenia 548
blackouts, alcoholic 404, 443
Bleuler, Eugen 522, 531, 603, 631, 1546–7blindness, hysterical 1017blood alcohol concentration 442, 448
blood transfusion and Creutzfeldt–Jakob 
disease transmission 355, 356, 358
BMI see body mass index
BMP (bone morphogenetic protein) 156
bodily distress disorder 1000, 1000 , 1003
epidemiology 1003, 1004
bodily preoccupation
in body dysmorphic disorder 1043–4
in hypochondriasis 1022
body, dislike of 57
body awareness disorders 57
body dysmorphic disorder (BDD) 57, 1043–9
association with aggression and 
violence 1044
childhood and adolescence 1045
classiﬁ  cation 1022, 1045

clinical features 1043–5
comorbidity 1044–5
course 1046
cross-cultural aspects 1045
delusional 618, 1044, 1045
diagnosis 1045–6, 1045
epidemiology 1046
and gender 1045
and hypochondriasis 1045
non-delusional 1045and obsessive–compulsive disorder 1044, 
1045
pathogenesis 1046
and pregnancy 1116
prevalence 997–8, 998
prevention 1048
prognosis 1046
puerperal 1120
and requests for cosmetic treatment 
1046, 1096
and suicidality 1044
treatment and management 1046–8
body image
distortion 57
disturbance 783and eating disorder 57
organic changes in 57
body mass index (BMI) 784
in anorexia nervosa 784, 794
and depression 1674
body weight
in anorexia nervosa 782, 784
in bulimia nervosa 803, 804
Bolam test 1902, 1905
bone morphogenetic protein 156
bonobo 812
Borago ofﬁ  cinalis  (borage) 1248

bonobo 812
borderline personality disorder 866–8
aetiology 867
and bulimia nervosa 803, 804
childhood and adolescence 1673
classiﬁ  cation 856, 867, 867

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022borderline personality disorder ( cont.)
clinical features 867–8
comorbidity 868, 884, 902
course and outcome 868, 892
and deception 1049
diagnosis 867–8
differential diagnosis 682, 865, 866, 868, 
871, 874
elderly people 1562 , 1563
epidemiology 867, 882, 883
following head injury 391
treatment 318–19, 868, 894–7, 898, 902, 903, 
904, 905–6, 905, 1364–5
borderline personality organization 867
boredom and substance use disorders 427
Borrelia burgdorferi  1094–5
Boston Diagnostic Aphasia Examination 89
Boston Naming T est 89Botswana, life expectancy 1507
bouffée délirante  603, 604, 606
with symptoms of schizophrenia 605
boundaries of self, awareness of 56
boundary violation 1338
bovine spongiform encephalopathy 
351, 352, 355
Bowlby, John 242, 309–10, 1725
boxing 395
BPSDs (behavioural and psychological 
symptoms in dementia) 412–17, 413,414
Brachman-de Lange syndrome see de Lange 
syndrome
brachycephaly 1839
bradyphasia 53

boxing 395
syndrome
bradyphrenia in brain tumour 1075brain
activation during sexual arousal 819
alcohol-related damage 182–3, 399–402 ,
444, 1541
anatomy 144–56
in anorexia nervosa 781
anoxia 1091
applications of PET 187–8in autism 1636
congenital anomalies 538
in delusional disorder 614
in delusional misidentiﬁ  cation 
syndrome 623–4
development 156–7, 157
effects of substance use disorders 429–30, 429
fear and anxiety circuit 754–5
glucose metabolism 187–8
hemispheric shape and formation of gyri 159histogenesis 158–9
hypoperfusion in depression 660
injury see head injury
ischaemia 387
magnetization 191mapping 187–8
and mind 133–6
and psychodynamic psychiatry 315–16
neural induction 156
neuronal death 387
neuronal networks 201–5
in obsessive–compulsive disorder 768oedema 387, 1084–5
pathology see neuropathology

regional blood ﬂ  ow 187–8
in frontotemporal dementia 347, Plate 12and neural activity 197regions involved in attention 246
reward circuit 430
in schizophrenia 562–4, 563
tumours 407, 942, 1075, 1929
in vascular dementia 376
visual areas 147, 152
see also speciﬁ  c areas
brain-derived neurotrophic factor 160, 171, 
225, 652, 966, 1199, 1201, 1674, 1684
brain fag syndrome 982–3
brain slices 202–3
brainstem 150–1
histogenesis 158
in mood disorders 182
Brazil, attitudes to psychiatric disorder 6breastfeeding 1120
and opioid use 480
pharmacotherapy 1123
antidepressants 675
benzodiazepines 1121, 1170
dosage regimens 1169–70
breathing retraining in panic disorder 761breeder effect 549

bremelanotide in sexual dysfunction 828
Brief Cognitive Rating Scale 1240
Brief Disability Questionnaire 284
brief dynamic therapy 720brief focal psychotherapy 1327, 1330–1, 1331
Brief Psychiatric Rating Scale 70, 524, 1164
brief psychodynamic psychotherapy 
see psychodynamic psychotherapy, brief 
(short-term)
brief psychotic disorder 606, 695
brief reactive psychosis 870
brief solution-focused therapy 1276
brief supportive therapy 720
Brief Symptom Inventory 1164bright light therapy in dementia 414
Briquet’s syndrome 999
British Crime Survey 1984
Brixton T est 90
broad-focus short-term dynamic 
psychotherapy 1333
Broca’s area 144, 146, 153, 153
Broca’s dysphasia 1527
brofaromine
pharmacodynamics 1187 , 1188
bromides 1178

4-bromo-2,5-dimethoxyphenethylamine 501bronchodilators 730, 1101
brucellosis 1095
BSE (bovine spongiform encephalopathy) 
BST (brief supportive therapy) 720
Building Bridges project 1411
bulbo-urethral gland 817
bulimia nervosa 800–11
aetiology 805–7
anxiety in 803
assessment 807
attitudes to shape and weight 803binge eating in 801–2
and child sexual abuse 780childhood and adolescence 1784classiﬁ  cation and diagnosis 800–1, 801
clinical features 801–4
course and outcome 809
depression in 803, 804
development 805
and diabetes mellitus 804dieting in 801–2
epidemiology 804–5, 805
general psychopathology 803–4
genetics 806
impulse control problems in 803
maintaining factors 807, 1299
neurobiology 806–7and obesity 804
origins of the concept 800
overlap with anorexia nervosa 800, 801

perfectionism in 804, 806
and personality disorder 803, 884
physical features 804
and pregnancy 1118
purging/non-purging 802–3
risk factors 805–6, 806
self-esteem in 804, 806
and substance use disorders 804, 806
treatment and management 807–9, 1193–4, 
1298–303, 1323–4, 1784
weight control methods 802–3
buprenorphine 475, 1244
detoxiﬁ  cation 476–7
maintenance treatment 476, 479
metabolism 473in pregnancy 1118
prescription 479
in substance use disorders 429–30
bupropion 670, 671
adverse effects 1190–1, 1191
in body dysmorphic disorder 1047
in childhood and adolescence 1676dosage 1195, 1196
in panic disorder 757
pharmacokinetics 1189, 1189
in smoking cessation 512
burglary, victims of 1986
burns see accidents

Burton, Richard, Anatomy of Melancholy
629–30, 630
buspirone 1178, 1181, 1212
in generalized anxiety disorder 735, 737
pharmacodynamics 1172in social anxiety disorder 743
Butler Report 2015
butobarbitone 1178
butyrophenones in pregnancy 1118
BzRAs see benzodiazepine receptor agonists
2C-B 501
2C-T2 501
CACE estimation 142
caffeine, addictiveness 431
CAGE 1519, 1542
Cajal–Retzius cells 148, 158
calcitonin gene-related peptide 206

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022calcium carbimide 453
calcium-channel blockers, L-type 1200–1, 1201, 
1203, 1203
see also  nimodipine
California Verbal Learning T est 253, 264
calorie restriction and modiﬁ  cation of 
ageing 1509
CAM (Confusion Assessment Method) 
328, 1531
Camberwell Assessment of Need 94, 1434
Camberwell Family Interview 268Cambridge Mental Disorders of the Elderly 
Examination 336
Cambridge Neuropsychological T est Automated 
Battery 255, 263
Cambridge–Somerville Study 1910
Cambridge Study in Delinquent 
Development 1908, 1909, 1910, 1911, 
1912, 1912–13
CAMDEX 336
CAMHS see mental health services, child and 
cAMP (cyclic adenosine monophosphate) 175
Camphill communities 1392
CAN (Camberwell Assessment of Need) 
94, 1434
Canada, attitudes to psychiatric disorder 6
cancer 1100–5
and alcohol consumption 446and anxiety 1101–2, 1101
childhood and adolescence 1743
delirium in 1103–4, 1104
fatigue in 209, 210

94, 1434
and mood disorders 649, 1102, 1102 ,1103
parental, effects on child development 
1754–5
and suicide 1102–3
candidiasis, systemic 997
cannabinoids
endogenous 429
receptors 173, 1171
cannabis 507–10 , 515
acute psychological effects 507
amotivational syndrome associated 508
behavioural effects in adolescence 508
chronic psychological effects 507cognitive effects 92, 507–8
dependence 507
and ﬂ  ashbacks 508
patterns of use 507
psychosis 507, 538
and schizophrenia 507, 546
cannibalism 351, 354
CANTAB (Cambridge Neuropsychological T est 
Automated Battery) 255, 263
CANTAB Paired Associate Learning test 
264, 266
CANTOUs 1583
capacity
and cognitive assessment 90–1
and consent to surgery 1096–7Council of Europe Principles Concerning

264, 266
capacity
and consent to surgery 1096–7Council of Europe Principles Concerning 
the Legal Protection of Incapable 
Adults 1896
elderly people 1577
following head injury 397independent advocate 1898
and juvenile delinquency 1954–5lack of 1898–9
legal aspects 1895–900
tests of 1897
Capgras syndrome 335, 392, 610, 623
CAPS (Clinician Administered PTSD Scale) 703
Caracas Declaration 1427
carbamazepine 1198, 1200, 1233–5
adverse effects 1200 , 1204, 1233–4, 1867–8
in bipolar disorder 671, 672
in childhood and adolescence 1677
choice of 1866
in dementia 415
dosage and administration 1233 , 1234–5
drug interactions 1175, 1205–6, 1232, 1234, 
1234 , 1866
indications and contraindications 1234
mechanism of action 1200
monitoring therapy 1176
overdose 1234
pharmacokinetics 1203, 1233, 1867
pharmacology 1201, 1202 ,1203 , 1233
in pregnancy 1118, 1234

response correlates 1199
in schizophrenia 591
structure 1232
therapeutic proﬁ  le 1199
withdrawal 1206–7, 1234
carbon monoxide poisoning 406–7, 973carcinoid tumours 1101
card-sorting games 1778
‘cardiac invalidism’/‘cardiac neurosis’ 1025, 
1138, 1559
cardiac myopathy in alcohol use disorders 446Cardinal Needs Schedule 1434
cardiovascular disease 1081–2
in alcohol use disorders 446
cardiovascular system, in chronic fatigue 
syndrome 1038
care management, in mental health social 
work 1410–11
care programme approach (CPA)
in community mental health services 1455, 
1456 ,1457
to manage risk of homicide 1939
in services for people with intellectual 
disability 1888
caregiver-mediated interventions 1787–93
adolescents 1790
background 1787
mediators of efﬁ  cacy 1790–1

pre-natal and early childhood 1787–8
preschool years 1788–9school-aged children 1789–90
carers
in Alzheimer’s disease 339
burdens on 1401
in dementia 417–18effects of personality change following head 
injury 391
of elderly people with intellectual 
disability 1880–1
impact of caring on 1465of people with alcohol use disorders 
452–3, 465
role in treatment of intellectual disability 1873
Carers and Users Experience of Services 1434
cargo-cult syndrome 982CARITAS principles 1580Cartesian dualism 133, 989
CAS (childhood apraxia of speech) 1712
case ascertainment 283
case-control studies 282
case-ﬁ  nding 541
case management 584, 1402, 1455castration
chemical 838
and libido 815–16
surgical 838
castration anxiety 294CAT see cognitive analytical therapy
CAT (community alcohol team) model 461

catalepsy 58, 58
cataplexy
misdiagnosis 928
with narcolepsy 940–1
catastrophizing 1137–8
catatonia 58
elderly people 1531excited 529
malignant 529, 1254
retarded 529
treatment 1254
catecholamines
in cocaine use 485and depression 1185, 1185
effects on memory 409
in methamphetamine use 497
in post-traumatic stress disorder 706
category fallacy 276Catherine of Siena, St 777
caudate nucleus 154, 159, 1684
CBD see corticobasal degeneration
CBGT (cognitive-behavioural group therapy) 
742, 744
CBT see cognitive-behaviour therapy
CDsee conversion disorder
CDCS see cri-du-chat syndrome
CDR (Clinical Dementia Rating) scale 1535
CDRPs (Crime and Disorder Reduction 
Partnerships) 515
CDRS-R (Children’s Depression Rating Scale, 
Revised) 1675
CEA see cost-effectiveness analysis

CEACs (cost-effectiveness acceptability 
curves) 1475, 1475
Center for Epidemiologic Studies Depression 
Scale 284, 1675
central nervous system
malformations leading to intellectual 
disability 1832
organogenesis 156–7, 157
central pontine myelinolysis 445
central sleep apnoea 1083central state materialism 134
central sulcus 144–5
centromeres 223
cephalic ﬂ  exure 156
CER see control event rate; cost-effectiveness 
ratio
CERAD (Consortium to Establish a Registry 
for AD) 336
cerebellum 155
development 157, 157
effects of alcohol use disorders 445histogenesis 158

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022cerebellum ( cont.)
and memory 254
cerebral contusions 387, 388, 389
association pathways for hearing 147, 152
association pathways for somatic 
sensation 146, 152
association pathways for vision 147, 152
commissural connections 151
effects of alcohol use disorders 444
general connectivity pattern 149–50, 149
histogenesis 158–9, 159
olfactory pathways to 147, 152
speech areas 153, 153
structure and organization 144–8, 145,
146,147
subcortical afferents to 150–3, 153, Plate 2
subcortical efferent pathways 154–6, 154
cerebral palsy 1740
cerebrasthenia 1060
cerebrospinal ﬂ  uid 157
in anorexia nervosa 782
in frontotemporal dementias 347in HIV-associated dementia 385
in mild cognitive impairment 1538
cerebrovascular disease
and amnesia 407
and vascular dementia 366, 378, 378
cervical ﬂ  exure 156
CES-D (Center for Epidemiologic Studies 
Depression Scale) 284, 1675

CFS see chronic fatigue syndrome
CGA (common geriatric assessment) 1581CGRP (calcitonin gene-related peptide) 206
challenging behaviour in dementia 413–15
Change for Children Programme 1946
character 79
analysis 299–300assessment 80–1, 80, 82–3
deﬁ nition 847
development 84
dimensions 80–1, 80, 316
and personality 316–17psychoanalytic approaches 295–6
Charcot, Jean-Martin 20–1
Charles Bonnet syndrome 1531
‘chasing the dragon’ 473
chemokines 168, 171
chemotherapy, anticipatory disorders 1101
chien  1420
child abuse and neglect 1731–9
and adoption outcome 1750
characteristics of abused child 1734, 1736
characteristics of abusers 1734–5, 1736, 
1736–7
and chronic pain 1033
and conduct disorder 1660
emergency presentation 1810
epidemiology 1732
and factitious disorder 1051
false and recovered memories 713–15

1736–7
and ﬁ  licide 1125
and hypochondriasis 1025
induced factitious disorder 1054, 1697, 1737, 
1923–4
and mental health social work 1409
and mood disorders 1675neglect 1735–6and offending 1910
physical abuse 1734–5
prevention 1737–8, 1788
psychodynamic theories 316
psychological maltreatment (emotional 
abuse) 1736–7
role in aetiology of psychiatric disorder 286
treatment and management 1738
child and adolescent mental health services 
see mental health services, child and 
Child Behaviour Checklist 1718
child-care 1727
child guidance movement 1381
child molesting (paedophilia) 832, 833,836,
1960–1, 1962
child pornography 1961
child protection
and psychiatric reports 75
role of school 1814
Child PTSD Symptom scale 1730
child sexual abuse
aetiological factors 1733
characteristics of abused child 1733

characteristics of abusers 1733
clinical features 1732
course and prognosis 1733, 1734
deﬁ nition 1732
diagnosis 1732–3and eating disorders 780
false accusations 834
false and recovered memories 713–14, 834prevalence 1960
and sexual dysfunction 825
within-family 1733
childbirth 1118–20
post-traumatic stress disorder 
following 1121
querulant reactions to 1121
acute behavioural disturbance 1810
acute stress disorder 1729adjustment disorders 721–3
1741, 1742
diagnostic criteria 1669–71, 1671
adolescents 1945
interviewing 1601
adverse experiences 271–2, 1724
and borderline personality disorder 867
and mood disorders 648, 658–9
aggression, severe maladaptive 1798
alcohol use disorders 456, 464

antisocial behaviour 1654, 1945–59
anxiety
assessment 1665with intellectual disability 1851–2
with physical illness 1742–3
anxiety disorders 1664–9
clinical course 1666
clinical presentation 1665–6
comorbidity 1666, 1673differential diagnosis 1671
art therapy 1414assessment 90, 1600–6content of the clinical interview 
mood disorders 1675
need for multiple informants 1600
‘at risk’ children 1803
behavioural effects of cannabis in 
adolescence 508
bereavement 235, 1758–60

differential diagnosis 1645, 1657environmental risk factors 1675
body dysmorphic disorder 1045
borderline personality disorder 1673
cancer 1743caregiver-mediated interventions 1787–93
chronic fatigue syndrome 1745–6, 1784
chronic renal failure 1741, 1743
classiﬁ  cation 104, 1589–94
cognitive assessment 90
cognitive-behaviour therapy 1767, 1777–86
anxiety disorders 1668, 1779–80
attention-deﬁ  cit hyperactivity 
disorder 1782–3
chronic fatigue syndrome 1784
conduct disorder 1781–2
depression 1675–6, 1780–1
eating disorders 1784
failure to engage/respond 1779following attempted suicide 1707
inclusion of cognitive component 1778–9
non-organic pain 1784

obsessive–compulsive disorder 1686–7, 
1686 , 1783–4
post-traumatic stress disorder 1784
psychiatric/behaviour disorder with 
substance abuse 1784
technique and management 1778working with parents 1778–9
cognitive therapy 1610, 1767, 1783
comorbidity in 1591, 1600confusional state 1742
conversion disorder 1745
counselling 1764–9
approaches to 1766–8
measures of effectiveness and outcome 1769practical issues 1768
in psychiatric/behaviour disorder and 
supportive 1767
training and supervision 1768–9
treatment setting and process 1766
cross-gender behaviour 1718–19
cyclothymic disorder 1671, 1672
cystic ﬁ  brosis 1743
deﬁ nitions and terminology 1764–5
deliberate self-harm 972, 1601, 1703

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022depression
acute management 1677
assessment and monitoring 1675, 1780–1
course 1673
diagnostic criteria 1669, 1670
differential diagnosis 1657, 1671–3
double 1673
environmental risk factors 1675
minor 1669neurocognitive factors 1674–5
neuroendocrine studies 1675
sequelae 1674
treatment and prevention 674–5, 1322, 
1668, 1675–6, 1780–1, 1794–5, 1796
developmental disorders 1591, 1591
see also  speciﬁ  c developmental disorders
developmental history 1600–1, 1822
diabetes mellitus 1741disruptive (externalizing) disorders 1591, 
1591 , 1654
dysthymia/dysthymic disorder 683, 1669, 
1670 , 1673
eating disorder
atypical 787
differential diagnosis 1672treatment 1784
see also speciﬁ  c eating disorders
effects of parental mental/physical illness on 
development 1752–8
electroconvulsive therapy 1256emergencies in 1807–11
emotional (internalizing) disorders 1591, 
1591 , 1654

1591 , 1654
environmental factors affecting mental 
health 1724–8
child care 1727
family 1725–7
peers 1727
schooling 1727
social 1727–8
epidemiology of psychiatric disorders 1594–9
epilepsy
aetiology 1619–20
classiﬁ  cation 1619
clinical features 1618–19course and prognosis 1618–19, 1620
diagnosis 1619
differential diagnosis 1619
epidemiology 1619
with intellectual disability 1861 ,1863 , 1864
management 1620
prevention 1620
psychiatric disorder associated 1740
salient non-epileptic episodes 1861
estimating the burden of psychiatric 
disorders 1595–6
factitious disorder in 1050
factors related to development of chronic 
pain 1033
factors related to development of 
hypochondriasis 1025
gender identity disorder 1718–23
aetiology 1719–20
assessment 1721
clinical features 1718–19epidemiology 1718

pain 1033
longitudinal studies 1720–1and mental disorder 1721treatment 1721–2
group therapy 1768
head injury 394–5, 1616–18
headache 1745
health promotion in 1610
Huntington’s disease in 372–3
hypersexuality 1671
and antisocial behaviour 1946
and anxiety 1851–2
and bereavement 1759
and depression 1852
effects on family 1883–4
prevalence 1878psychiatric and behaviour disorders 
associated 
1849–53 , 1879
special needs of adolescents 1878–80
transition to adulthood 1878–9
interests/hobbies/talents 1601
juvenile delinquency see juvenile delinquency
and life events 1601looked after children 1799–802
mania 1670–1, 1675, 1677
media exposure 1601
medical history 1601
mental health services see mental health 
services, child and adolescent (CAMHS)
mental status examination 1601, 1602
mood disorders 1669–80

clinical picture 1669–71, 1670 ,1672
comorbidity 1673
with intellectual disability 1852neurocognitive factors 1675
treatment and prevention 1675–7
natural emotional healing 1765–6
neuropsychiatric disorders 1612–22
neuropsychological assessment 1590–1, 1605
obsessive–compulsive disorder 1613, 
1680–93
aetiology 1683–5
age of onset 1681classiﬁ  cation 1682
clinical features 1680–1
comorbidity 1681–2
course and prognosis 1685
diagnosis 1682–3differential diagnosis 1682–3
epidemiology 1683
and gender 1681
with intellectual disability 1852
prevention 1690refractory 1688
treatment 1685–90, 1686 ,1687 , 1783–4
opioid dependence 480
pain in 1744–5
persistent somatoform pain disorder 1745pharmacotherapy 1793–9

antidepressants 674–5, 1668, 1676, 
antipsychotics 1677, 1796–8, 1852
atomoxetine 1795–6developmental issues 1794
dosage regimens 1169
mood stabilizers 1798, 1852as part of multimodal treatment 1793–4with psychiatric/behaviour disorder and/or 
intellectual disability 1798, 1852
rapid tranquillization 1798
stimulants 1795
symptom-based approach 1794
effects of psychiatric disorder on course 
and outcome 1744
psychiatric disorder associated 1740–3
post-traumatic stress disorder 237–8, 
1728–31 , 1741, 1744, 1759, 1784, 1851–2
prevention in 1606, 1609–11
psychodynamic psychotherapy 1769–77
background 1770
classical technique 1770–1
deﬁ nition 1764
efﬁ cacy 1773–4
indications and contraindications 1772limitations 1774
managing treatment 1772–3
procedure selection 1772

psychodynamic technique 1771–2
psychopathic personality 1950
psychoses
differential diagnosis 1673
psychotherapy 1764–9 ,1769–77
conﬁ  dentiality 1768
consent for 1765
and culture 1768
differences from adult psychotherapy 
1765, 1765
ending 1768failure to attend 1768
focus on past vs. focus on present 1767
individual vs. group therapy 1768
involvement of parents and school 1768
limit-setting vs. free expression 1767measures of effectiveness and 
outcome 1769
record-keeping 1768
treatment setting 1766
reaction to death of a parent 1758–60
relationship between physical and mental 
health 1739–47
residential care 1799–802
role of child psychiatrist in schools and 
colleges 1811–16
schizophrenia 1613

risk factors for development 556–7
sleep disorders 1693–702
assessment 1696–7, 1696
developmental effects 1695
effects on parenting and the family 
1694–5
excessive daytime sleepiness 
1699–701, 1700
manifestations 1695
misinterpretation 1695
parasomnias 1701–2parental inﬂ  uences 1694
patterns of occurrence 1695
risk factors 1697–8
sleeplessness 1698–9
treatment and prognosis 1695–6
sleep physiology 1693–4

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022childhood and adolescence ( cont.)
social anxiety disorder 740, 1664, 1666
social functioning 1593
somatization and somatization disorder 
1744, 1744
special educational needs 1815
speciﬁ  c phobia 1664, 1665, 1666, 1741, 1742
speech and language disorder 1710–17
substance use disorders 1600, 1604
differential diagnosis 1672
treatment 1784
suicide and attempted suicide 1674, 1702–10
aetiology 1705–6, 1705 ,1706
assessment 1703–4
associated diagnoses 1704
clinical features 1703course and prognosis 1706
epidemiology 1704–5
prevention 1708–9
treatment 1706–8
temperament 235, 238, 238, 1601, 1665, 1667
in intellectual disability 1850
terminal illness 1743–4
therapeutic communities 1397tic disorders 1073, 1680–93
age of onset 1681
classiﬁ  cation 1682
clinical features 1681comorbidity 1681–2
diagnosis 1682–3
differential diagnosis 1682–3
epidemiology 1683and gender 1681

prevention 1690
treatment 1685–90
T ourette syndrome 1613, 1680–93
trauma in 1601, 1697, 1728–31 , 1744, 1762
victims of criminal activity 1986–7
wish for behavioural change in 1600
witnesses, children as 1761–3
childhood apraxia of speech 1712
childhood disintegrative disorder 1637
Children Act 1989 1732
Children’s Depression Inventory 1675, 1780
Children’s Depression Rating Scale, 
Revised 1675
Children’s Global Assessment scale 1593Children’s Memory Scale 89, 89
Children’s PTSD Inventory 1730
Children’s Revised Impact of Events scale 1730
Children’s Y ale-Brown Obsessive-Compulsive 
Scale 1681
China
neurasthenia as diagnostic entity 1061, 1062
and Pavlovian theory 1061
psychiatric nurses in 1407
Chinese Classiﬁ  cation of Mental Disorders  1062

China
Chinese traditional medicine 1249
chloral 1178
chloramphenicol 1091
chlordiazepoxide 1178
in alcohol withdrawal 449, 449
pharmacokinetics 1172
chlormethiazole see clomethiazole
chlorpromazine 1209, 1209 , 1262
administration 1213–14, 1214adverse effects 1212 , 1222
in cancer 
1104
development 1208–9pharmacodynamics 1211
cholecystokinins 171, 171
in generalized anxiety disorder 734
in panic disorder 754
cholesterol and suicide 966
cholinergic anti-inﬂ  ammatory pathway 206
cholinergic system
and alcohol-related brain damage 400in Alzheimer’s disease 338, 1240–1
anticholinergic action at 1225
antipsychotic actions on 1210, 1211
and cortical function 150, 151
and delirium 330, 1532
in depression 660
effects of PCP on receptors 487in head injury 388

and memory 253
and neurotrophic factors 160
in schizophrenia 180
cholinesterase inhibitors
in Alzheimer’s disease 1240–1, 1538
in dementia 415in dementia with Lewy bodies 366–7
in vascular dementia 381
cholinomimetics in Alzheimer’s disease 1241chorea 371
chorea acanthocytosis 373
Christian religious healing 1420
chromatids 223
chromatin remodelling 225chromosomes 218, 223
anomalies 1831
autosomal 218, 223
rearrangements 228–9, 1831
recombination 223, 226sex see sex chromosomes
telomere loss 1508
chronic benign pain syndrome 1003
chronic cutaneous dysaesthesia 618
chronic fatigue syndrome (CFS) 1035–43
aetiology 1038–40, 1040
assessment 1040–1
attribution to organic disease 1039
case formulation 1041

childhood and adolescence 1745–6, 1784classiﬁ  cation 1003, 1036–8
clinical features 1036, 1036
controversial aspects 990coping strategies 1039
course 1040
diagnosis 1036–8, 1041
differential diagnosis 1041
epidemics 1038
epidemiology 997, 1038
genetics 1038
international consensus deﬁ  nition 1037
overlap with psychiatric syndromes 1037–8
pathophysiology 1038–9
and personality 1039
prevalence 1038
prevention 1042prognosis 1040psychopathology 1039–40and sleep disorder 1697
and somatization 1039
and stigma 1039–40
treatment and management 1034, 1040–2, 
1041 , 1784
chronic obstructive pulmonary disease 
932, 1082
chronic renal failure 1087
childhood and adolescence 1741, 1743and sleep-wake disorders 932
chronic stress reaction and post-traumatic 
stress disorder 706
CI (conﬁ  dence interval) 126, 128

CIDI (Composite International Diagnostic 
Interview) 69, 70, 72, 284, 542, 1023, 1438
cimetidine 1532CIND see cognitive impairment, non-dementia
cinnarizine 1240circadian rhythms 1260
and bipolar disorder 647disorders 1261
effects of ageing 1572
sleep–wake 925, 926
circle time 1814
circular causality 1371
circular questioning 1387
circular sulcus 145
circumstantiality 53
citalopram 670
in body dysmorphic disorder 1046
in cancer 1102 ,1103
in childhood and adolescence 1676
in depression in elderly people 1554, 1554
in obsessive–compulsive disorder 1687
in panic disorder 756
pharmacodynamics 1186, 1187
pharmacokinetics 1188–9, 1189
CIWA-Ar (Clinical Institute Withdrawal 
Assessment for Alcohol-Revised 
Version) 1542
CJD see Creutzfeldt–Jakob disease

CJITS (Criminal Justice Integrated T eams) 515CL psychiatry see consultation-liaison (CL) 
Clarke Sex History Questionnaire for 
Males 1962
classiﬁ  cation 99–121
in childhood and adolescence 1589–94
conceptual issues 99–100deﬁ nition 99
development of systems 100–2
and diagnostic instruments 64
and epidemiology 1607
goals 99history of 631
in primary care 1483–4
Classiﬁ  cation of Violence Risk 1996, 1998
claustrophobia 52
claustrum 151Claviceps purpurea  487
see also  hydergine
cleft lip/palate 1711, 1712
Client Service Receipt Inventory 1474
clinical assessment see assessment
Clinical Dementia Rating scale 1535
Clinical Institute Withdrawal Assessment for 
Alcohol-Revised Version 1542

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022clinical neuropsychology 262
clinical practice guidelines 123, 124
Clinician Administered PTSD Scale 703
Clinician Assessment of Fluctuation Scale 363
clinophilia 939
clitoris 812, 817–18, 822
clobazam 1080, 1172
clomethiazole 1246–7
pharmacokinetics 1170
clomipramine 670
adverse effects 1191 , 1687
in body dysmorphic disorder 1046, 1047
in depersonalization disorder 775dosage 1196
769–70, 1193, 1687, 1687
in panic disorder 756, 756
pharmacodynamics 1173 , 1186, 1187
clonazepam 1080
in cancer 1102
in panic disorder 756, 757
in REM sleep behaviour disorder 947in social anxiety disorder 743
clonidine 1245
disorder 1651

in intellectual disability 1876in opioid detoxiﬁ  cation 477
in tic disorders 1073, 1688
‘closed-loop’ tasks 254
clozapine 1209
administration 1214 , 1215–16
adverse effects 1212 , 1223–4
in childhood and adolescence 1797in intellectual disability 1875
pharmacodynamics 1172, 1211 , 1213
pharmacokinetics 1172 , 1221
in schizophrenia 580, 582, 592
‘Club House’ 1453CMHCs (community mental health 
centres) 1454
CMHTs see community mental health teams
CNS (Cardinal Needs Schedule) 1434
cobalamin deﬁ  ciency 1087–8
cocaine 482–6
aetiology of use 484
classiﬁ  cation of disorders relating to 
483, 484
cognitive effects 92
complications associated 484–5course and prognosis of use 484–5
diagnosis of use 483–4
epidemiology of use 484

483, 484
in pregnancy 1118, 1615–16
prevention of misuse 485
psychosis due to 485, 538routes of use and risk associated 430, 483
treatment and management of use 485
Cochrane Collaboration 123–4, 578Cochrane Database of Systematic Reviews 1156–7
Cochrane Library 1156–7
codeine 430
metabolism 473–4in opiate abuse 1244
coenaesthesia 50coenestopathic states 1030
Cofﬁ  n–Lowry syndrome 1839
behavioural and psychiatric aspects 1842
genetics 1842
physical characteristics 1842
prevalence 1842
COGA (Collaborative Study on the Genetics of 
Alcoholism) 435
cognitive analytical therapy (CAT) 903–4, 1278
borderline personality disorder 895
cognitive assessment 85–94
in alcohol abuse and dependence 92
attention 60, 88–9
and capacity 90–1
childhood and adolescence 90
with intellectual disability 1850

in dementia 92
in depression 92
in drug abuse 92–3ecological validity 92, 92
elderly people 1527
in epilepsy 92
estimating premorbid ability 90, 90
frontal and executive functions 89, 90
generalizability theory 92
intelligence 87, 88
language 89
and malingering 91memory 89, 89, 253, 254, 255–6, 264, 
420–1, 420
in parkinsonism 92
principles 85–7, 85,86
protocol 91, 91
in schizophrenia 93, 265, 531–4
sources of tests and test data 89
speed of processing 87–8, 88
understanding and choice of tests 89–90
see also  neuropsychological assessment
cognitive-behaviour therapy (CBT)
acute stress reactions 697
adjustment disorders 720, 1068
anxiety disorders 1285–98
in childhood and adolescence 1668, 1779–80
attempted suicide 970
for auditory hallucinations 1314, 1317
bipolar disorder 673

body dysmorphic disorder 1047
childhood and adolescence 1767, 1777–86
failure to engage/respond 1779
following attempted suicide 1707
post-traumatic stress disorder 1784psychiatric/behaviour disorder with 
technique and management 1778
working with parents 1778–9
in chronic fatigue syndrome 1030, 1042
comparison with other 
psychotherapies 1321, 1333–4, 1333
compulsive buying/shopping disorder 916
computerized 1406conversion disorder 1019

and counselling 1277delusions/delusional disorder 1314, 1315–17, 
1315 , 1920
depersonalization disorder 775
depression 672–3, 676, 1304–13
advantages of 1304
background 1304
childhood and adolescence 1675–6, 1780–1
demands of 1304
in elderly people 1555ending treatment 1310–12
indications and contraindications 1305–6
management of treatment 1307–12, 
1308 ,1309
selection for 1306–7
technique 1304–5
eating disorders 792, 796, 808, 808–9, 
1298–303 , 1784
in generalized anxiety disorder 735–6
guided self-help 808–9
historical development 1286in HIV/AIDS 1092
hypochondriasis 1026–7
insomnia 935–6, 936
obsessive–compulsive disorder 770, 1686–7, 
panic disorder 758, 761

persistent somatoform pain disorder 1034personality disorders 903–4
antisocial 898
avoidant 897
borderline 895
post-concussion syndrome 396provision by psychiatric nurses 1406
for refugees 1497
schizophrenia 582–3, 1313–18
sex offenders 1963
juvenile 1953
social anxiety disorder 741–2, 742, 744
somatization disorder 1008–9, 1009
substance use disorders 428, 1784
therapeutic alliance in 903, 1307
tic disorders 1686–7
training 1297, 1312
trauma-focused 708–9, 1109, 1111, 1730with victims of criminal activity 1988
cognitive-behavioural group therapy 742, 744
cognitive control in insomnia 936
cognitive deﬁ  cits and distortions
in anxiety disorders 1779
disorder 1782
in conduct disorder 1781in depressive disorders 1780–1
in obsessive–compulsive disorder 1783

malingered 1055–6

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022cognitive development 1777–8
and developmental psychology 238–40, 239
history-taking 1600
cognitive dissonance and the placebo 
response 1142
cognitive dysmetria 563
Cognitive Estimates T est 90
cognitive impairment
in Alzheimer’s disease 334–5
in autism 1633
cannabis-associated 92, 507–8due to disturbed sleep 926
following head injury 390–1, 395
following stroke 1071
in frontotemporal dementias 347
mild see mild cognitive impairment
in multiple sclerosis 1074
non-dementia 1519, 1520, 1521 , 1535, 1535 ,
1536, 1537
vascular 378–9
in Parkinson’s disease 368
postoperative 1099prior to surgery 1098
in schizophrenia 93, 265, 528, 531–4 , 580
in schizotypal personality disorder 533
cognitive models of illness 1138cognitive neuropsychology 262
cognitive neuroscience 262
cognitive reactivity 1304
cognitive restructuring
in anxiety disorders 1293, 1293
in generalized anxiety disorder 736

in panic disorder 761
in sleep disorders 937, 1572
in social anxiety disorder 742social anxiety disorder 742
cognitive schemas 52, 1778
maladaptive 1778
early 895
negative 1304
and reporting of physical symptoms 1137
cognitive stimulation in dementia 414
Cognitive T est for Delirium 326
cognitive theory
and somatization disorder 1005
cognitive therapy 310, 311, 1940
childhood and adolescence 1610, 1767, 1783and concept of depression 15
and counselling 1277
for delusions 1980
family-based 1707
group setting 1351history of 23
in morbid jealousy 1920
personality disorder 903–4
post-traumatic stress disorder 708–9schizophrenia 1315–17, 1315 , 1317
substance use disorders 428

see also  cognitive-behaviour therapy
Cognitive Therapy Scale 1311
Cohen–Mansﬁ  eld Agitation Inventory 413
cohort 1513
cohort studies 282, 283, 541, 557, 568collaborative care 1483, 1486, 1487in adjustment disorders 1068
Collaborative Study on the Genetics of 
Alcoholism 435
collagen, cross-linkage 1508
colleges
psychiatrist as advisor 1815
see also  schools
coma 59
following head injury 388
Glasgow Coma Scale 388, 388
commissural plate 157
commissure of the fornix 151
common geriatric assessment 1581
communication
doctor–patient 1138–9in intellectual disability 1873
skills training 1139, 1375–6
communication disorders see speciﬁ  c 
developmental disorders, of speech and language
community, prevalence of mental disorders 1480
community alcohol team model 461
community care 584

global survey 11
history of 24
and rehabilitation 1400
community diagnosis 280
community mental health centres 1454Community Mental Health in ID Service 1888–9
community mental health teams (CMHTs) 584, 
1454–5, 1456 ,1457 , 1458
services for people with intellectual 
disability 1888–9
see also  mental health services, community
community outreach in attempted suicide 
970, 972
community psychiatric nurses (CPNs) 1404–5
in treatment of alcohol use disorders 462see also  psychiatric nurses
community reinforcement 456, 462
community substance misuse teams 479
community treatment orders 1411, 1458
comorbidity 278, 990
in childhood and adolescence 1591, 1600
in primary care 1483
see also under speciﬁ  c disorders
compartmentalization phenomena 1012, 1012
compensation claims
and conversion disorder 1016

and persistent somatoform pain disorder 1034
‘compensation neurosis’ 700
competence 29
abilities involved 1897best interest approach 1899
functional approach 1898
and juvenile delinquency 1954–5
lack of 1898–9
legal aspects 1895–900outcome approach 1897–8
status approach 1897, 1899–900
complementary medicines 15, 1247–51
antipsychotics 1249
anxiolytics and sedatives 1248
in chronic fatigue syndrome 1042
in chronic somatic conditions 1249
cognitive enhancers 1247–8
determinants of pharmacological 
properties 1248
and diagnosis 65drug interactions 1249–50, 1250
mood disorders 1248
in movement disorders 1249
in neurasthenia 1063
psychoses 1249
smoking cessation 512in substance use disorders 1249
‘complex medically ill’ 1144
complex regional pain syndrome, type I

complex regional pain syndrome, type I 
1015, 1050
Complexity Prediction Instrument 1145
Complier-Average Causal Effect of 
Treatment 142
Composite Disability Malingering Index 
1054–5
Composite International Diagnostic 
Interview 69, 70, 72, 284, 542, 1023, 1438
Comprehensive Psychopathological Rating 
Scale 70
COMPRI (Complexity Prediction 
Instrument) 1145
compulsions 52, 53, 1680
in body dysmorphic disorder 1044, 1044
in obsessive–compulsive disorder 765–6
computed tomography (CT)
alcohol-related dementia 400
anorexia nervosa 781
epilepsy 1619frontotemporal dementias 347
head injury 389
HIV-associated dementia 385
obsessive–compulsive disorder 768
schizophrenia 563–4vascular dementia 376
Wernicke–Korsakoff syndrome 400, 406
COMT gene 255, 256, 555, 559, 1646concealment of treatment allocation 127

concentration
assessment 60, 88–9
concentration camp survivors 1494
conditioning 250, 254, 258
in acute stress reactions 696
and post-traumatic stress disorder 705
and substance use disorders 428, 434
conduct disorder 1654–64
adolescent onset 1655, 1658
adult outcome 1660–1, 1660
aetiology 1658–60
and age 1655assessment 1657, 1781–2
classiﬁ  cation 1656–7
clinical features 1655–6
comorbidity 1644, 1657conﬁ  ned to the family context 1656
course 1660–1
depressive 1657
differential diagnosis 1657, 1671
early-onset 1655, 1656, 1658, 1788
and outcome 1660, 1660
epidemiology 1658
and gender 1655, 1658
genetics 1658
hyperkinetic 1644, 1657

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022and intellectual disability 1657, 1851
and juvenile delinquency 1946
life-course persistent 1658
pattern and setting of behaviour 1655
and perinatal complications 1658
prevention 1663, 1788
prognosis 1660–1
protective factors 1660
and pulse rate 1658
relation to other disorders 1654
risk factors 1658–60
role of neurotransmitters 1658as a social problem 1654–5
socialized 1656
treatment and management 1661–3, 1781–2
unsocialized 1656
verbal deﬁ  cits in 1658
wider impact of 1655–6
conduction dysphasia 54
confabulation 59, 403, 408, 1049
following head injury 392
momentary/provoked 408
in post-traumatic stress disorder 404
spontaneous 408
in Wernicke–Korsakoff syndrome 405
conﬁ  dence interval 126, 128
conﬁ  dentiality
assessment 1605
psychiatric emergencies 1811
psychotherapy 1768
and clinical assessment 67
and domestic violence 1982and expert witnesses 2006–7
in factitious disorder 1053

in higher/further education 1815
in the paraphilias 840
and reports 75in schools liaison service 1813
confounding factors 285
confrontation in factitious disorder 
1052–3, 1053
Confusion Assessment Method 328, 1531confusional state 59
in childhood and adolescence 1742
following an accident 1110
disorder 1268
post-ictal 403
see also  delirium
congenital rubella syndrome 548, 1635, 1850, 
1852, 1863
congestive heart failure in anorexia nervosa 785
congophilic angiopathy 338Conners’ Parent Rating Scale 1241, 1645
Conners’ T eacher Rating Scale 1241, 1645, 1813
connexions advisors 1812
conscientiousness 850, 886
conscious mental states 135conscious thinking 294
clouding of 59, 59, 60
concept of 59
disorders of 59–60heightened 59

loss of following head injury 388
narrowing of 60
consent see informed consentConsortium to Establish a Registry for AD 336
constipation and depression 641
consultation
communication in 1138–9
in consultation-liaison psychiatry 1145
patient-centred/doctor-centred 1139
consultation-liaison (CL) psychiatry 990, 1135, 
1144–8 , 1487
audit 1147
current levels of service delivery 1144
for elderly people 1583
Psych-Med unit 1145
screening in 1145–6, 1146
service organization 1146–7, 1147
stafﬁ ng 1146
training 1147types of service delivery 1145–6, 1145 ,1146
container-contained theory 308
contiguous gene syndromes 228
contingency management in opioid 
dependence 477
continuous performance tests 247
contracts in psychoanalysis 1341
control
delusions of 51, 56
perceived lack of in generalized anxiety

control
perceived lack of in generalized anxiety 
disorder 734
control event rate 128
contusions, cerebral 387, 387, 389
conversion 1012
pain as form of 1031–2
conversion disorder (CD) 57, 1011–21
childhood and adolescence 1745
chronic 1017classiﬁ  cation 106, 993, 994
clinical features 1014–17
comorbidity 870, 1015
and culture 14–15
deﬁ nitions 1012, 1012
differential diagnosis 695, 1003, 1012, 1012
epidemiology 998, 1014
examination 1015–16
mimicking surgical conditions 1096
and pain 1031–2pathophysiology 1013–14, 1013 ,1014
prognosis 1017–18
role of volition 1012sleep-related 948
treatment and management 1018–20, 1019
conversion symptoms 57
Cool Kids programme 1779
cooperativeness 80, 80, 83, 316, 850
cooperatives 1401
Coordinators of Services for the Elderly 
project 1584
COPD (chronic obstructive pulmonary 
disease) 932, 1082
COPE programme 1779

coping
active/engaged/approach 1066
behavioural 1066
with depression 1306
emotion focused 1066
failure 1067
with illness 1065–71
and immune function 207
passive/disengaged/avoid 1066
problem focused 1066with schizophrenia 1313–14, 1315social 1066
in social anxiety disorder 744and somatization disorder 1009styles 1066
techniques 1066
with terminal illness 1069–70
Coping Power Programme 1662, 1782coping strategy enhancement 451, 1313–14, 
1315, 1662, 1782
coprolalia 1073, 1681
copropraxia 1073
Cornell scale for depression in dementia 413coronary heart disease
and alcohol consumption 446
and type A personality 1136
and type D personality 1136
corpus callosum 151, 157, 180
corpus striatum 158, 159
correlation coefﬁ  cient 849
Corsi blocks 255

cortical dysplasia 159, 1863
cortical plate 158
corticobasal degeneration (CBD) 344
aetiology 348differential diagnosis 347–8
neuropathology 345
corticobulbar pathway 156
corticopontine pathway 155
corticospinal tract 156, 158corticosteroids
in childhood and adolescence 1673
psychosis 539
release in response to stress 1135
corticostriate pathway 154–5, 154
corticotrophin-releasing hormone (CRH) 
163, 171
and depression 163–4, 166, 659, 661
and immune function 206
and suicide 965
cortisol
and aggressive/antisocial behaviour 1918
and chronic fatigue syndrome 1039
and depression 660–1, 1675
and ﬁ  bromyalgia 1039
in generalized anxiety disorder 732
hypersecretion 1086

and the sleep–wake cycle 925
COSE project 1584
cosmetic psychopharmacology 28–9
cosmetic treatment in body dysmorphic 
disorder 1046, 1096
cost-beneﬁ  t analysis 1474, 1475
cost-consequence analysis 1475
cost-effectiveness acceptability curves 
1475, 1475
cost-effectiveness analysis (CEA) 
1463, 1474, 1475
alcohol use disorders services 462–3
child and adolescent mental health 
services 1476–7
mental health interventions in developing 
countries 1477, 1478
research study design 1475–6

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022cost-effectiveness ratio, incremental 
124, 1475, 1475
cost-per-QALY approach 1475, 1476
cost-utility analysis (CUA) 1474, 1475
of depression treatment in primary care 1476
costs, measurement of 1474–5
Cotard’s syndrome 56
Council of Europe, Principles Concerning the 
Legal Protection of Incapable Adults 1896
counselling 1272–85
adjustment disorders 721, 1278alcohol use disorders 1279
anxiety 1278
applications 1278–80
bereavement 726–7, 1279
childhood and adolescence 1764–9
measures of effectiveness and 
practical issues 1768
cognitive–behavioural models 1275, 1277
cognitive models 1275
core conditions 1274–5
couple 1370
deﬁ nitions 1273
depression 672, 676, 1278
eclectic-integrative approaches 1278
in educational settings 1281
effectiveness 1274

electronic delivery 1282existential approaches 1277
following abortion 1119
genetic see genetic counselling
grief 726–7, 1279
in HIV/AIDS 1280–1in hospitals and clinics 1280–1
humanistic–existential models 1275, 1276–7
information-giving in 1275–6
key elements and goals 1273
methods and techniques 1275–8mothers giving up children for adoption 1120
pathological gambling 922
person-centred (client-centred) 1275, 1276–7
postnatal depression 1280
practice 1274in primary care 1280, 1485–6
psychodynamic models 1275, 1277–8
and psychotherapy 1273–4, 1765
rape victims 1986
in relationship problems 1278–9schools of 1275, 1275
settings 1280–2, 1485–6
skills 1274
smoking cessation 511–12
stress disorders 1278substance use disorders 1279
telephone helplines 1282
theoretical approaches to 1275, 1275

therapeutic alliance in 1275
training, accreditation and 
registration 1282–3
trauma 1279–80
in the voluntary sector 1279, 1281
in the workplace 1281–2
counselling psychology 1274counterfeit deviance 834–5
countertransference
in brief psychodynamic psychotherapy 
1329, 1330
broad/totalistic view 314, 315
complementary 1343
concordant 1343
joint creation 314, 315
narrow view 314, 315
and non-compliance 317
object-relations theory model 298–9in physician-assisted suicide 318
and projective identiﬁ  cation 308
in psychoanalysis 1343–4
and psychodynamic psychiatry 314, 315, 318
Countertransference Questionnaire 1344
couple counselling 1370
couple therapy 1365–6, 1369–80
adjustment disorders 
1069
alcohol use disorders 452–3assessment and selection 1373
behavioural 452–3, 1371
behavioural–systems 1372–8

1069
cognitive-behavioural 1371
and culture 1377–8
depression 15, 672
distinction from couple counselling 1370efﬁ cacy 1378–9
indications and contraindications 1373
intersystem model 1372
mixed/eclectic approach 1371–2
paraphilias 838, 840process 1373–5
psychoanalytic/psychodynamic 1370–1
psychodynamic–behavioural 1372
rational–emotive 1371
substance use disorders 516systems approach 1371
techniques 1375–7
training in 1379
Court of Protection 1898–9
Court reports 1928, 2004 ,2005–6
courtship behaviour 815
COVR (Classiﬁ  cation of Violence Risk) 
1996, 1998
Cowper’s gland 817
CPA see care programme approach
CPNs see community psychiatric nurses
CPSS (Child PTSD Symptom scale) 1730
CR (calorie restriction) and modiﬁ  cation of 
CR/HT (crisis resolution/home treatment) 
teams 1458, 1458

crack 430, 431, 483
see also  cocaine
cranial nerve development 157
‘crashing’ 497craving 427, 428, 483
cre recombinase 230
creatinine 1204
creative thought 308
Creutzfeldt–Jakob disease (CJD) 351, 1903
aetiology 351–2
amyotrophic 354
ataxic 354
atypical 354
Heidenhain’s variant 354
iatrogenic 353, 355
panencephalopathic 354
prevention 358–9sporadic/classical 352, 353–4, 353
variant 351, 353, 355–6
secondary (iatrogenic) 353, 356
CRH see corticotrophin-releasing hormone
cri-du-chat syndrome (CDCS)
crime analysis 1914Crime and Disorder Act 1998 1982, 1987–8
Crime and Disorder Reduction 
Partnerships 515
criminal activity see offending
Criminal Damage Act 1971 1966

Criminal Justice Integrated T eams 515
criminal liability 1900–1
Criminal Procedure (Insanity and Fitness to 
Plead) Act 1991 1901
criminal victimization 1984–90
criminogenic factors 1911, 1917, 1918, 
2011, 2012
crisis cults 982crisis houses 1458
crisis resolution/home treatment teams 
1458, 1458
criterion variance 284
Crohn’s disease 1083–4
cross-cultural comparisons 276, 277
cross-fostering study 216
cross-sectional studies 282
crowding of thoughts 53
CRPS I (complex regional pain syndrome 
type I) 1015, 1050
cryptographia 54
cryptolalia 54
crystal/crystalline methamphetamine 
hydrochloride 497–8
CTsee computed tomography
CTOs (community treatment orders) 1411, 1458
CUA see cost-utility analysis
cue exposure in alcohol use disorders 451
CUES (Carers and Users Experience of 
Services) 1434

‘cult of thinness’ 779
cultural competence 1502–4, 1503
culture
and ageing 1512–13
and body dysmorphic disorder 1045
and care pathways 1438–45
in child and adolescent psychotherapy 1768
and the concept of depression 15and conversion hysteria 14–15
and couple therapy 1377–8
cultural critique of biomedicine 276–7
cultural formulations 278
and deliberate self-harm 958–9and depression 14, 1496
and help-seeking behaviour 15, 1441–2
and hypochondriasis 1025–6
and indigenous folk healing practices 1418
and intellectual disability 1879–80, 1881and mania 14
and marriage 1370
and mental health services for ethnic 
minorities 1502–4

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022and neurasthenia 1060–1
and neuroses 14
and normal sexual function 812–13
and the phenomena of psychiatric 
disorder 47
and provision of services 277–8and reaction to loss of a parent 1758
and refugee assessment, diagnosis and 
treatment 1496, 1496 , 1498
role in caregiver-mediated 
interventions 1791
and schizophrenia 14, 546, 557, 571–3, 572
and social and cultural anthropology 275–9
and somatization disorders 996and stigma 6–7
and suicide 953–4, 1704
transcultural psychiatry 13–16
and treatment 1442–3
culture of blame 1991–2
culture-related speciﬁ  c psychiatric 
syndromes 14, 979–85 , 1439
acute and transient psychotic disorders 606
anorexia nervosa as 779
concept of 979
subgroups 979–80, 980
in western societies 984–5
current awareness 124–5, 125
Cushing’s syndrome 1086
CVLT (California Verbal Learning T est) 253, 264
CY-BOCS (Children’s Y ale-Brown Obsessive-
Compulsive Scale) 1681
cyberstalking 1970‘cyber suicide’ 1706

cyclic adenosine monophosphate 175
d-cycloserine
adverse effects 1091
in social anxiety disorder 743in speciﬁ  c phobia 746
cyclothymia/cyclothymic disorder 632, 686–9
aetiology 688–9
childhood and adolescence 1671, 1672
clinical features 687–8course 687–8
diagnosis 687–8
epidemiology 688, 689
historical perspective 686
management 689prevention 689
relationship to bipolar disorder 688
CYP system
and antidepressants 1188
and antipsychotics 1221, 1222
and complementary medicines 1249, 1250
inhibitors 1795and opioid metabolism 473–4
and pharmacokinetics 1170, 1172
cyproterone acetate 838, 1963–4
cytokines 168, 171, 209
cytomegalic inclusion disease 1863
cytosine 223
Da Costa syndrome 751
DAG (diacyl glycerol) 174, 175
DALE (Disability-Adjusted Life 
Expectancy) 1510

DALYs (Disability-Adjusted Life Y ears) 10, 645, 
1477, 1510
dangerous and severe personality disorders 848, 
2015, 2018DAPA-PC (Drug Abuse Problem Assessment for 
Primary Care) 1484
DAPP-BQ (Dimensional Assessment of 
Personality Disorders) 858, 858
DARE database 1156
DAS (Disability Assessment Schedule) 284
‘date rape’ 409, 491
DATs (Drug Action T eams) 515–16
DAWBA (Development and Well-Being 
Assessment) 1595–6
dawn-simulating alarm clock 1261
acute 1453
in Alzheimer’s disease 340
in anorexia nervosa 793, 795
in community mental health services 1453
daydreaming 294, 1941
DBS (deep brain stimulation) 671, 769, 1073–4, 
1258, 1269–70
DBT see dialectical behaviour therapy
DC-LD (Diagnostic Criteria for Psychiatric 
Disorders for Use with Adults

Disorders for Use with Adults 
with Learning Disabilities/Mental 
Retardation) 1826–7, 1850
de Lange syndrome
physical characteristics 1842prevalence 1842
de-affectualization 774
debrieﬁ  ng
critical incident stress 697
emergency workers 1110trauma story 1497
deceitfulness in conduct disorder 1656
decentring technique 1374
deception 1941
decision-making
and emotion 260–1
deep brain stimulation 671, 769, 1073–4, 1258, 
1269–70
deep lateral sulcus 144, 145
de-escalation techniques 1404
defence mechanisms 310, 849
avoidant 1339–40in brief psychodynamic psychotherapy 1328–9
classiﬁ  cation 1339–40
and personality development 316–17
primitive/mature 1339and psychoanalysis 293–4, 1339–40
and resistance 315, 317

defensive organizations 1339
dehydration and ecstasy use 495
de-ideation 774deinstitutionalization
and burden of care 1401
and intellectual disability 1881, 1887, 1890
and mental health social work 1408, 1411
and prevalence of mental disorder among 
and psychiatric nursing 1403
déjà vu  59, 250
delay aversion in attention-deﬁ  cit hyperactivity 
disorder 1647
delayed sleep phase syndrome 928, 942–3, 
1261, 1695, 1700
deliberate self-harm (DSH) 955, 957–63and adjustment disorders 718, 722
aetiology 960–1
and age 1704
in anorexia nervosa 782–3
assessment 971, 971
in childhood and adolescence 972, 1601, 1703choice of method 959–60classiﬁ  cation 960
clinical features 958
course and prognosis 961
deﬁ nition 957–8
elderly people 1551, 1564–7
epidemiology 958–60high-risk 960
impulsive 916–17

and intellectual disability 1856
and liability of mental health service 
providers 1905
lifetime prevalence 960
mild 960
moderate 960
in physical illness 1133
precipitants 961
prevention 972–6
repetition 961, 969, 971, 972
and risk of suicide 961, 971, 971,972
self-report surveys 960
sociodemographic characteristics 959
treatment 969–72
vulnerability factors 961
delineation of syndromes 281
délire d’emblée  603, 604
delirium 49, 325–33
aetiology 330, 330
at childbirth 1118in cancer 1103–4, 1104
and cholinergic system 330, 1532
classiﬁ  cation 105, 327, 1531
clinical features 326–7, 326
comorbidity 327and consciousness 59
and dementia 327, 329, 332, 1532
diagnosis 327–8
differential diagnosis 327–8, 328, 364
drug-induced 1532elderly people 1529, 1530–4
aetiology 1532, 1532
classiﬁ  cation 1531
clinical features 1530–1

complications 1533course and prognosis 1532
diagnosis 1531
differential diagnosis 1531, 1559epidemiology 1531–2
prevention 1533
treatment and management 1532–3
epidemiology 328–9
in HIV/AIDS 1092–3, 1093
hyperactive 327, 1531, 1532, 1533
hypoactive 327, 1530–1, 1532, 1533
investigation 330, 330
mixed 327
mortality risk 329
neuropathogenesis 330–1, 330
outcome 328–9
phencyclidine-induced 486–7
in pneumonia 1091
postoperative 1098–9post-seizure 1257

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022delirium ( cont.)
prevention 331, 1533
psychosis in 327
risk factors 329, 329
subsyndromal 325, 328, 1531
treatment and management 331–2, 1104 , 1255
tremor in 58
Delirium Rating Scale 1531
Delirium Rating Scale-Revised-98 328
Delirium Symptom Interview 1531
delirium tremens 58, 327, 443
prevention 450
treatment 449–50
delusional atmosphere 51
delusional disorder 609–28
aetiology 613–14
clinical features 613–15diagnostic criteria 103–4, 613, 613
differential diagnosis 864
elderly people 1552
erotomanic 621–2
features of delusions in 612
genetics 614
grandiose 622and homicide 1920
induced 610, 624–5
jealous 51, 619–21, 1920, 1967
litigious 616, 1977–80
mixed/unspeciﬁ  ed 623
and mood disorders 614
nomenclature 610–11
and offending 1920
persecutory 616
somatic 617–19, 1024and stalking 1920
subtypes 613, 613, 615–23
treatment 625–7, 1920
and violence 1920
delusional disorientation 392delusional intuition 51

delusional misidentiﬁ  cation syndrome 51, 392, 
609–10, 611, 622, 623–4
delusional perception 51, 527–8
delusional states, systematized 1030delusions 49
disorders 602–8
autistic 51autochthonous 51
in body dysmorphic disorder 618, 1044, 1045
clinical aspects 611–12
cognitive-behaviour therapy 
1314, 1315–17, 1315
content of 51
of control 51, 56
deﬁ nition 50–1, 611
in delirium 327
in delusional disorder 612
in dementia with Lewy bodies 361
dental 619
and depression 51, 639, 641, 674, 1253differential diagnosis of cause 537
of disease transmission 619
in frontotemporal dementias 346
genesis 51grandiose 51
of guilt 51of halitosis 618–19hypochondriacal 51
and jealousy 51, 619–21, 1920, 1967
of love 51

of love 51
memory 51, 59
millenniary 982
and misidentiﬁ  cation 51, 392, 609–10, 611, 
622, 623–4
mood-congruent/-incongruent 537, 641
nihilistic 56
as paranoid defence 1314
of parasitosis/infestation 50, 51, 618
in Parkinson’s disease 1072
of persecution 51
polarized 51
of pregnancy 1115
primary 51, 611religious 51
in schizophrenia 526–7
secondary 51, 611
of sexually transmitted disease 619of smell 618–19
structure of 51
and violence 1929
dementia 54
and ageing 1520
and aggression 336, 1920–1, 1928–9
agitation in 413–15
alcohol-related/alcohol-induced 
399–402 , 1541
apathy in 416
behavioural and psychological symptoms 
412–17, 413,414
carers 417–18
challenging behaviour in 413–15cholinergic hypothesis 338, 1240–1
cognitive assessment 92
deﬁ nitions 411

delaying onset 1538and delirium 327, 329, 332, 1532
depression in 416
differential diagnosis 1531
distinction from delirium 327, 328
distinction from depression 1551, 1551
disclosure of diagnosis 411
1865, 1880
and driving 412
early-onset 411–12, 1584elderly people
differential diagnosis 1558–9
early detection 1519–20
epidemiology 1519–22 , 1579–80
impact 1522incidence and risk factors 1520–2, 
1520 ,1522
presentation in primary care 1483
end-stage management 418
epidemiology 1579–80
frontotemporal (FTD) 258–9, 344–50 , 1519
aetiology and pathogenesis 348
and aggression 1928–9
behavioural and psychological 
symptoms 413
classiﬁ  cation 344, 347
clinical features 345–6
differential diagnosis 347–8, 347, 373
epidemiology 345genetics 348

investigations 347, Plate 12
Lund–Manchester consensus on clinical 
criteria 345, 345, 347
neuropathology 344–5
with parkinsonism 344–5, 346, 348
physical signs 346
treatment and care 348–9
genetic counselling and testing 411, 412
HIV/AIDS 384–6 , 1091
classiﬁ  cation 384
clinical features 384
course and prognosis 385
diagnosis 384–5
differential diagnosis 384–5
epidemiology 385
pathogenesis 385
severity levels 384
treatment and management 385–6
in Huntington’s disease 371–5
and intellectual disability 1827, 1828, 1855
with Lewy bodies (DLB) 361–8
clinical diagnosis 363–4, 363
clinical features 335, 361–2
course and prognosis 365
diagnosis 336
differential diagnosis 364, 364, 369
epidemiology 364–5
genetics 365
investigations 364management 365–7, 366

pathological classiﬁ  cation 362
pathological criteria 362
relationship with dementia in Parkinson’s 
disease 362–3
management 411–19
mania in 416
memory impairment 59
mixed pathologies 336
in motor neurone disease 344, 345, 347, 348
and offending 1920–1pain in 418
in Parkinson’s disease 92, 362–3, 368–71 ,370
psychomotor disturbance in 59
psychosis in 416
risk assessment and management 417, 417
risk reduction/protective factors 1521–2, 1522
semantic 344, 346severity stages 1535
sexual behaviour disorders 416
and sexuality 1568
and sleep-wake disorders 416–17, 931,
1572, 1573
structural MRI 195
subcortical 368–9
treatment
complementary medicines 1247–8
pharmacotherapy 1240–1
urinary incontinence in 417
vascular (VaD) 375–84 , 1519
acute onset 378

1572, 1573
treatment
aetiology 376
classiﬁ  cation 377
clinical criteria 377–8, 377,378

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022clinical features 379
cortical (multi-infarct) 375, 377, 378
course and prognosis 379
diagnosis 379–80
differential diagnosis 348, 364, 380
epidemiology 380–1
incidence 1520
mixed cortical and subcortical 378
NINDS-AIREN criteria 377, 378, 378
pathophysiology 376
prevention 381, 1447
risk factors 376
subcortical (small-vessel) 377, 378
treatment 381
wandering in 415
see also  Alzheimer’s disease
dementia infantilis 1637
dementia paralytica 1093
dementia praecox 522, 540, 568, 603, 631, 1547
see also  schizophrenia
DemT ect 1536
denial 298
in anorexia nervosa 783
as coping behaviour 1066
dental enamel erosion in bulimia nervosa 804
dentate gyrus 148
dentatorubropallidoluysian atrophy 228, 373
deoxyhaemoglobin 197
deoxyribonucleic acid see DNA
dependence
distinction between physical and 
psychological 427–8
spectrum of 427–8
dependent personality disorder 873–4
aetiology 873
classiﬁ  cation 856, 873, 873

clinical features 873
course 874
differential diagnosis 874elderly people 1562
epidemiology 874, 882, 883
treatment 874
depersonalization 55, 56, 1012
deﬁ nition 774
distinction between primary and 
secondary 775
epidemiology 775
following an accident 1107following head injury 392
in neurological disorders 775
victims of criminal activity 1984
depersonalization disorder 774–6
aetiology 775classiﬁ  cation 774
clinical features 774
course and prognosis 775
diagnosis and differential diagnosis 774–5
epidemiology 775treatment and management 775–6
deprenyl 385
aetiology
genetic 648, 650–8
integrated model 649
neurobiological 658–65
age of onset 667
and alcohol use disorders 649and anorexia nervosa 783, 787anticipation in 652
and antisocial personality disorder 866

and anxiety disorder 649
anxious 641–2, 642assessment 660
assessment instruments 69, 70, 1163–4, 1306, 
1484, 1551, 1552
atypical 635
and bereavement 725binary model 638
and body mass index 1674in bulimia nervosa 803, 804
assessment and monitoring 1617–16, 
1780–1
minor 1669
neurocognitive factors 1674–5
and childhood adverse experiences 648, 
658–9
chronic 667
and chronic fatigue syndrome 1037classiﬁ  cation 638–9, 640–2
clinical features 633–5, 633, 640–1

658–9
cognitive model 1304–5, 1305 , 1307
cognitive vulnerability to 1304concept of 15
and conversion disorder 1015
coping strategies 1306
and corticotrophin-releasing hormone 
163–4, 166, 659, 661
and cortisol 660–1, 1675
course 271, 667
and culture 14, 1496deﬁ nition 637
in dementia with Lewy bodies 361, 367
diagnosis 647, 1306
differential diagnosis 327, 328, 643–4, 741, 
766, 1004, 1024, 1531
distinction from dementia 1551, 1551
double 681, 683, 1673
drug-induced 1551, 1552
duration and severity of episodes 633–4, 667
dysfunctional cognition in 653
elderly people 1550–6
aetiology 1552 , 1553
assessment 1527, 1551–2
clinical features 1551
in the community 1517
course and prognosis 1553
diagnosis 1551–2
differential diagnosis 373, 1552, 1558

epidemiology 1517–18, 1552–3, 1579
factors inﬂ  uencing presentation 1551
in hostels and nursing homes 1518
investigations 1551–2, 1553
mortality associated 1553prevention 1555–6
in primary care 1482–3, 1518
resistant 1555
treatment and management 674, 1554–5
endogenous/melancholic 630, 631, 638, 
640–1
epidemiology 647–9 , 650–1
following an accident 1109–10following ecstasy use 495
following head injury 393, 396
following miscarriage 1119
functional anatomy 189, 660
and gender 271, 648, 653–4
and generalized anxiety disorder 731global disease burden 645, 1185
history of 629–30
hostile 641–2, 642
and intellectual disability 1827, 1852, 1854–5
and juvenile delinquency 1949

and kleptomania 1943
and life events 269–73, 270,
271, 648, 659
lifespan perspective 271–2
maintaining factors 659–63major
classiﬁ  cation 639
diagnosis 647
with psychotic features 634, 639
recurrent 634stages leading to 634
with/without melancholia 634
and marital conﬂ  ict 1753
and marital status 648
masked 1030, 1527melancholic 270
minor 668
models 638–9monoamine theory 662
mortality associated 667–8
and neurasthenia 1063
neuroendocrine challenge tests 660
neurotic 270, 638, 641offenders 1923, 1933
outcome 667
and pain 1029, 1030
and panic disorder 752
1752–3
and patient state ﬂ  uctuations within mood 
disorders 632–3, 632,633
and persistent somatoform pain disorder 997
and personality 648
and personality disorders 649
pharmacogenetics 653in physical illness 648–9, 1132

Alzheimer’s disease 335
cancer 649, 1102, 1102 ,1103
COPD 1082
Cushing’s syndrome 1086diabetes mellitus 649, 1085
epilepsy 1080
HIV/AIDS 1092
Huntington’s disease 371
hyperthyroidism 1085hypothyroidism 1085
infection 1091
multiple sclerosis 1074

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022depression ( cont.)
in physical illness ( cont.)
myocardial infarction 649, 1082
Parkinson’s disease 648–9, 1072
population perspective 272–3, 272
post-hysterectomy 1116
post-psychotic 589, 626
post-stroke 1071, 1555
precipitating factors 659
in pregnancy 653, 1117, 1322
prevalence 647–8primary 637
detection and assessment 1476
elderly people 1518
treatment 1322, 1476
prisoners 1923, 1933
psychosocial factors 271, 653
psychotic/delusional 51, 639, 641, 674, 1253
reactive 630, 631, 638, 641
recurrence 634–5, 667, 671
in refugees 1495relapse 671
remission 271
resistant 675, Plate 14
risk factors 648–9, 658–9, 1675
in schizophrenia 529, 573seasonal 635
secondary 637
and shoplifting 1943
situational 642and sleep-wake disorders 634, 661–2, 927, 
931, 931, 934, 1697
social functioning in 653
spectrum model 642and substance use disorders 649
subsyndromal symptomatic (SSD) 719

subtypes 630, 631, 638, 640–2, 640, 647
and suicide 634, 955, 1704
and temperament 654, 658in terminal illness 1070
thyroid abnormalities in 661
treatment 669–77
cognitive-behaviour therapy 672–3, 676, 
1304–13 , 1555, 1675–6, 1780–1
combined psychotherapy and 
pharmacotherapy 672–3
continuation 671, 675, 677counselling 672, 676, 1278
deep brain stimulation 671, 1270
electroconvulsive therapy 671, 1252–3
in HIV/AIDS 1092
interpersonal psychotherapy 672–3, 676, 
1322–3, 1555, 1676
maintenance 671, 675–6, 677
management 673–7
marital therapy 672
neurosurgery 1267, 1268in primary care 1476
in resistant depression 675
setting 673
transcranial magnetic stimulation 
671, 1264
vagus nerve stimulation 671, 1269
see also  antidepressants and speciﬁ  c drugs

671, 1264
treatment gap 13tryptophan depletion 662
unipolar
deﬁ nition 638
history of concept 631
as unitary disorder 638
and use of mental health services 649
vascular, elderly people 1551, 1553
depressive condition, deﬁ  nition 637
depressive episode disorder 633
depressive equivalent 1030
depressive personality disorder 878–9
depressive position 307
deprivation and psychiatric disorder in 
intellectual disability 1828
derailment 53
derealization 56, 774, 1012
dermatotillomania (pathological skin 
picking) 618, 917–18 , 1044
Descartes, René 133, 989
description, personal and subpersonal 
levels 135
descriptive phenomenology 47–61
deﬁ nition 47
disorders of attention and 
concentration 60

levels 135
disorders of consciousness 59–60
disorders of intellectual performance 54
disorders of memory 59
disorders of mood 54–5disorders of perception 48–50
disorders of personality 60
disorders of self and body image 56–7
disorders of thinking 50–4
language and speech disorder 53–4motor symptoms and signs 58–9
principles 47–8
theoretical bases 48
desensitization
in obsessive–compulsive disorder 770systematic 1097
designer drugs 494
desipramine 670, 1185
adverse effects 1191 , 1193
pharmacokinetics 1172 , 1188, 1189
desomatization 774
detachment phenomena 1012
Determinants of the Outcome of Severe Mental 
Disorders 14, 572, 572
devaluation 298
developing countries
cost-effectiveness analysis of mental health

cost-effectiveness analysis of mental health 
interventions 1477, 1478
prevalence of intellectual disability 1825
Development and Well-Being 
Assessment 1595–6
Developmental Behaviour Checklist 1850
Developmental Behaviour Checklist for 
Adults 1828
and schizophrenia 548see also  pervasive developmental disorders; 
speciﬁ  c developmental disorders
developmental neuropsychiatry 1612–22
developmental perspective
environmental risks 1724–8
pharmacotherapy 1794
in psychodynamic psychiatry 314
reasons for taking 234–5
developmental psychology 234–45
cognitive development 238–40, 239, 1777–8
critical issues 235–7
and effects of parental mental/physical 
illness 1752–8
and individual differences 238
language development 240–1, 241, 1623,

language development 240–1, 241, 1623, 
1710–11
memory development 241–2, 241–2
models and theories 234–5
neonatal/early infancy stage 238–9
social and emotional development 
242–3, 
242
stage theories 234–5, 239–40, 239
developmental psychopathology 237–8, 
1612–13
and attachment 243and classiﬁ  cation in childhood and 
adolescence 1589–94
and epidemiology 1608
in infancy 238–9linking to developing children 238–42
Piaget’s work 239–40, 239
developmental scales 1821
developmental stages 1764, 1777
developmental toxicology 1614deviance, subcultural 1657
dexamethasone, in generalized anxiety 
disorder 732
dexamethasone–CRF test 164, 1252
Dexamethasone Suppression T est (DST)
in depression 661, 1252
in elderly people 1552
dextroamphetamine

disorder 1648
dhat  606, 981
diabetes insipidus, lithium-induced 1204
diabetes mellitus 1085
and bulimia nervosa 804
in childhood and adolescence 1741
depression in 649, 1085
and schizophrenia 546sexual dysfunction in 826
diacetylmorphine see heroin
diacyl glycerol 174, 175
diagnosis 99–121
additional/subsidiary 74
alternative 74and clinical assessment 64–5, 74
and complementary medicine 65
cultural critique 276–7
deﬁ nition 99
differential 74

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022and disorder 64–5
division between medical and psychiatric 
989–90, 992
ethical issues 28–9
main 74
multiaxial systems 73, 100–1, 990, 990
provisional 74
role of value judgement 29
and social control 29
diagnosis related groups 1430
Disorders, development 100–2
Disorders, DSM-II
hypochondriasis 1022
neurasthenia 1060
Disorders, DSM-III 26, 631
alcohol dependence and alcohol abuse 437
autism 1633
bulimia 800
depression 638–9development 100–1
dysthymic disorder 1060
generalized anxiety disorder 729–30
multiaxial descriptive systems 100–1
panic disorder 751post-traumatic stress disorder 693
schizophrenia 1547
sexism in 28
somatoform disorders 105, 993–4, 999, 1022
Disorders, DSM-III-R 101
alcohol dependence syndrome 437
depression 639
panic disorder 751, 752

personality disorders 855–6, 856
post-traumatic stress disorder 693
Disorders, DSM-IV 113–20
acute PCP intoxication 486acute stress disorder 693, 694, 694
adjustment disorders 106, 716, 717–19, 
717, 1067
alcohol use disorders 439, 440
Alzheimer’s disease 336attention deﬁ  cit-hyperactivity disorder 1643
bipolar disorder 639
body dysmorphic disorder 1045–6
categorical approach 849
as classiﬁ  cation of disorders 64
communication disorders 1623, 1623
comparison with ICD-10 102–4
cultural critique 276
and cultural formulation 278
cyclothymic disorder 686delirium 327, 1531
delusional disorder 609, 613, 613
delusions 611
depersonalization disorder 774
depression 633, 633, 639, 640
development 101–2

disorders relating to cocaine 483, 484
dysthymic disorder 681
eating disorder 106, 787–8, 800–1, 801
ethical issues in diagnosis using 28
factitious disorder 106, 1049, 1050
frontotemporal dementias 348generalized anxiety disorder 730, 730impulse control disorders 911
intellectual handicap 1820, 1820
learning disorders 1623, 1623
malingering 1054
mania 635, 635
mental retardation (intellectual 
handicap) 1820, 1820
motor skills disorder 1623, 1623
multiaxial descriptive systems 73obsessive–compulsive disorder 765, 1682
panic disorder 750–1, 751, 752
pathological gambling 920
personality disorders 106, 851, 855–8, 856
antisocial personality disorder 865
avoidant personality disorder 872
borderline personality disorder 867
dependent personality disorder 873

histrionic personality disorder 869
narcissistic personality disorder 871
obsessive–compulsive personality 
disorder 874, 874
paranoid personality disorder 861, 861
passive–aggressive personality 
disorder 876, 876
schizoid personality disorder 863, 863
schizotypal personality disorder 864, 864
pervasive developmental disorders 1633, 
1639
post-traumatic stress disorder 701, 702–3 , 703
in primary care 1483–4relational problems 1382
schizoaffective disorder 597–8
schizophrenia 105, 534, 534,536, 541, 
568–9, 571
sexual dysfunction 823
social anxiety disorder 740
somatoform disorders 993–4, 993, 1003, 1062
conversion disorder 106, 1012
hypochondriasis 996–7, 1022–3, 1022
persistent somatoform pain disorder 
993–4, 1029–30
somatization disorder 996, 999–1000, 1003

speciﬁ  c phobia 745
substance-induced persisting dementia 
399, 399
substance use disorders 439, 440
tic disorders 1682
use in epidemiology 283
vascular dementia 377, 377
Disorders, DSM-IV-PC 1483–4
Disorders, DSM-IV-TR 102
bereavement 1758in childhood and adolescence 104, 1592–3
conduct disorder 1657
intellectual disability 1825
intellectual disability with psychiatric 
disorder 1826, 1849, 1850
and stressors 718
structure 104–6
Disorders, DSM-V , research planning 
for 106–8, 852
Diagnostic Criteria for Psychiatric Disorders for

Diagnostic Criteria for Psychiatric Disorders for 
Use with Adults with Learning Disabilities/Mental Retardation 1826–7, 1850Diagnostic Criteria for Research  71
Diagnostic Interview for Personality 
Disorders 858
Diagnostic Interview Schedule 71–2, 542, 765
dialectical behaviour therapy (DBT) 304
attempted suicide 970, 1707
personality disorders 318–19, 868, 895–6, 
904, 1563
diazepam 1178
in alcohol withdrawal 449
in delirium 1533dosage 1180
drug interactions 1232
as a hypnotic 1182
pharmacokinetics 
1172 , 1178
rebound and withdrawal symptoms 1180–1
didanosine 1091 , 1092
diencephalon 156
diet
and attention-deﬁ  cit hyperactivity 
disorder 1646–7, 1648
elderly people 1529
elimination 1648
and modiﬁ  cation of ageing 1509

diet
and monoamine oxidase inhibitors 1187–8, 
1192, 1192
difference scores 87
abnormality 87
reliability 87
differential reinforcement of other 
behaviour 414
diffuse axonal injury 387
digit span 89, 255, 264
digoxin 1532
dihydrocodeine 474, 1244
dihydroergotoxin 1240dihydrotestosterone 815
diltiazem 1201, 1206
Disorders 858, 858
2,5-dimethoxy-4-ethylthio-
β-phenethylamine 501
dimethyltryptamine 488, 489, 501
diminished responsibility defence 1901, 1922, 
1923, 1928, 1937, 1939, 1940
Dioscorea alata  1249
DIPD (Diagnostic Interview for Personality 
Disorders) 858
diphenhydramine 1226
direct questioning in child and adolescent 
assessment 1604–5
DIS (Diagnostic Interview Schedule) 71–2, 
542, 765
deﬁ nition 389
measurement of 1465

542, 765
Disability-Adjusted Life Expectancy 1510
Disability-Adjusted Life Y ears 10, 645, 1477, 1510Disability Assessment Schedule 284
disablement 283
concepts of 65, 66
measurement of 284
disasters 1108DISC1 gene 229, 555
discrimination 11
and stigma 5, 6, 7

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022disease, concept of 62, 63–4, 277–8
disinhibition
and hallucinations 50
disintegrative psychosis 1637
disorientation 59
delusional 392
disposable soma theory 1509
dissocial personality disorder see antisocial 
dissociation 1012, 1013
in acute stress reactions 693, 694, 696
following an accident 1106–7
dissociative disorder see conversion disorder
dissolution du langage  346
disulﬁ  ram 453,730,1246 , 1542
diuretic abuse
in anorexia nervosa 784
in bulimia nervosa 802, 803
diurnal rhythm disturbances 55
divalproex 1677divination 1420
divorce 1369–70, 1601, 1726
counselling 1278–9
DLB see dementia, with Lewy bodies
DMIS (delusional misidentiﬁ  cation syndrome) 
51, 392, 609–10, 611, 622, 623–4
DNA
cloned 231
cross-linkage 1508
deletions/insertions 227
free radical damage 1509

DNA
cloned 231
hybridization 226methylation 224, 1508
microsatellites 226
mitochondrial (mtDNA) 223, 1832
age-related defects 1508
non-coding sequences 218
nuclear (nDNA) 223
accumulated somatic mutations 1508
pooling 221
replication 223short tandem repeats (STRs) 226
single nucleotide polymorphisms 
(SNPs) 218, 226, 227
structure and function 223
transcription 223–4, 224
effects of ageing on 1507
DNA microarray studies 1509, 1510
DNA repair genes 1508
doctor–patient communication 1138–9
domestic violence 1449, 1981–3
and conduct disorder 1659–60
during pregnancy 1117
Dominica, attitudes to psychiatric disorder 6
dommage par ricochet  1902
Domus units 1583donepezil
in Alzheimer’s disease 409, 1241, 1538

in Parkinson’s disease 370–1in vascular dementia 381
donor insemination 1114–15
Doose syndrome 1863–4dopamine agonistsadverse effects 539
in sexual dysfunction 828
dopamine dysregulation syndrome 1073
dopaminergic system and dopamine 
receptors 173, 511, 1171
and alcohol use disorders 229
antipsychotic actions at 1171–2, 1209, 
1210, 1211
in autism 1636
and cortical function 151
in delirium 330
dopamine transporters 169, 170
effects of amphetamines/cocaine on 482, 1172
effects of nicotine 510
effects of transcranial magnetic 
stimulation 1263
and novelty-seeking 886–7
in obsessive–compulsive disorder 767
PET/SPET imaging 186, 187, 188, 189–90
and schizophrenia 180, 188, 561–2and sexual function 826

in social anxiety disorder 741
and substance use disorders 429
in substance use disorders 429, 429, 436
and suicide 965–6and T ourette syndrome 1073, 1684
Doppelgänger 623
dorsal horn 157
dorsal parieto-frontal network 245
dorsal roots 158dosulepin (dothiepin) 670
‘double-bind’ 1053, 1381
double orientation 392
double phenomenon 56
Doublecortin 158Down syndrome
and autism 1839
behavioural phenotype 1613, 1839, 1851 , 1858
and dementia 1584, 1827, 1839, 1865, 1880
effects on the family 1883–4and epilepsy 1864, 1865
genetics 228, 1831, 1838–9
infantile spasms in 1863
and intellectual disability 1839
and mania 1826and parental psychiatric disorder 1885
physical characteristics 1839, 1850
prevalence 1825, 1838–9
prevention 1448
downward comparison 1066doxepin 670

drawings in child and adolescent 
assessment 1604
dreams
analysis 299, 306
dressing dyspraxia 1527
DRGs (diagnosis related groups) 1430
drift effect 549
drive-defence model 313
drive theory 294, 295, 302, 306drivingand dementia 412
elderly people 1577–8
legislation regarding alcohol consumption 
468, 469
measures to reduce casualties 468, 469
DRO (differential reinforcement of other 
behaviour) 414
droperidol 1209
pharmacodynamics 1211
DRPLA (dentatorubropallidoluysian 
atrophy) 228, 373
DRS-R98 (Delirium Rating Scale-
Revised-98) 328
Drug Abuse Problem Assessment for Primary 
Care 1484
Drug Action T eams 515–16
drug therapy see pharmacotherapy
DSH see deliberate self-harm

Care 1484
DSM see entries under  Diagnostic and Statistical 
Manual of Mental Disorders
DSPD 848, 2015, 2018
DST see Dexamethasone Suppression T est
dual instinct/drive theory 294, 295, 302, 306
dualism 133, 989–91
in psychopathology 848
behavioural and psychiatric aspects 1843
genetics 1843
physical characteristics 1843prevalence 1843
duloxetine 670, 670
adverse effects 1191 , 1555
duration of untreated psychosis (DUP) 536, 590
and prognosis 1459and response to treatment 573
Dyadic Adjustment Scale 1165
dynamic child psychotherapy see
psychodynamic psychotherapy, childhood 
dynorphin 171, 171
dysaesthesia, chronic cutaneous 618

dysarthria 53, 1711, 1712
dysbindin gene 179, 230, 555dyscalculia 1629–30
Dysexecutive Questionnaire 90
dysexecutive syndrome
assessment 89, 90
features 90
in parkinsonism 92in schizophrenia 93
dysfunctional assumptions 1286
Dysfunctional Attitudes Scale 1165
Dysfunctional Thoughts Record 1309–10, 
1309 , 1311
dyskinesias in Huntington’s disease 371
dyslexia 1627–9
surface 406
dysmorphophobia see body dysmorphic 
disorder
dysnomia 850dyspareunia 823

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022dysphasia 53
Broca’s 1527
conduction 54
and delirium 326
nominal 54, 334primary motor 54
primary sensory 54Wernicke’s 1527
dysphonia 53
dyspraxia
in Alzheimer’s disease 334
dressing 1527
dysprosody following head injury 391
dysthymia/dysthymic disorder 680–6 , 1060
aetiology 683–4
childhood and adolescence 683, 1669, 
1670 , 1673
classiﬁ  cation 681
clinical features 681–2, 682
concept of 680
course and outcome 668, 682–3, 683
diagnosis 681–2
epidemiology 683
historical perspective 680–1
and intellectual disability 1855interpersonal psychotherapy 1323
prevention 686
relationship with major depressive 
disorder 684, 684
treatment 684–6
dystonia
drug-induced 1222
psychogenic 1016
dystrobrevin-binding protein-1 555
EAPs (employee assistance programmes) 
1281–2
early infantile epileptic encephalopathy 1862
early intervention teams 1459, 1459

1281–2
early morning wakening in depression 
634, 661–2
early myoclonic epileptic encephalopathy 1862Eating Attitudes T est (EAT) 777
and body image 57
classiﬁ  cation and diagnosis 106, 800–1, 801
cognitive-behaviour therapy 792, 796, 808, 
808–9, 1298–303 , 1784
maintenance 1299 ‘not otherwise speciﬁ  ed’ 800, 801, 804
1753–4
relationships between 804
sleep-related 931, 947–8
temporal migration between disorders 801see also  anorexia nervosa; bulimia nervosa
Eating Disorder Examination 807, 1163
Eating Disorder Inventory 807

Ebstein’s anomaly 1118, 1169Echinacea purpurea  (echinacea) 1249, 1250echo de la pensée  49
echo phenomena 54, 58, 58
echolalia 54, 58, 58, 1681, 1713
echopraxia 58, 58
eclectic therapy 1278
ECLW Collaborative Study 1144, 1146ecstasy 494–7
neuropsychological impairment due to 496
neurotoxicity 496, 496
physical effects and complications 495, 495
pill testing 494
preparations and purity 494
prevalence and patterns of use 494–5
psychological effects and complications 
495–7, 495, 538
routes of use 494
ECT see electroconvulsive therapy
ectoderm 156
EDsee erectile dysfunction
Edinburgh Postnatal Depression Scale 1122
education
higher/further 1815

education
and intellectual disability 1873, 1884
role of the child psychiatrist 1811–16
school liaison service 1812–13
education welfare ofﬁ  cer 1812
educational psychologist 1812
EDUs (eating disorder units) 792–3
EEG see electroencephalography
EER (experimental event rate) 128efavirenz 1091
Effective Black Parenting Program 1791
effectiveness 1609
measurement of 1475
efﬁ cacy 1609
effort testing 1055, 1056
ego 294, 306, 313, 849
defences 297, 310
structure and functions 295–6, 316
ego ideal 296ego identity 295
ego psychology 295, 313, 1339
and mental health social work 1408–9
egocentricity 1777
eicosapentaenoic acid 1248EIS (early intervention teams) 1459, 1459
ejaculation 817
delayed 822
premature 822, 828
el miedo  984
elation in Alzheimer’s disease 335
abuse of 1575–6, 1575

adjustment disorders 1552
agoraphobia 1559alcohol intake recommendations 1540
alcohol use disorders 1519, 1540 ,
1540–2 ,1541
anxiety 1558–61
anxiety disorders 1531, 1579
art therapy 1415
assessment 1524–9after treatment 1528–9
common geriatric assessment 1581history-taking 1526
physical 1527–9
setting for 1525–7
bipolar disorder 1556–7
boundaries of normality 1574–5
capacity 1577cognitive assessment 1527
deﬁ nitions 1579
deliberate self-harm 1551, 1564–7
delirium 1529, 1530–4
clinical features 1530–1complications 1533
course and prognosis 1532
diagnosis 1531differential diagnosis 1531, 1559
epidemiology 1531–2
delusional disorder 1552
dementia

dementia
incidence and risk factors 1520–2, 
1520 ,1522
demography 333–4, 1517, 1517
dependence 1575–8
depression 1550–6
assessment 1527, 1551–2clinical features 1551
differential diagnosis 373, 1552, 1558epidemiology 1517–18, 1552–3, 1579
driving 1577–8dysphasia 1527
dysthymic disorder 1552
epilepsy with intellectual disability 1864
ethical issues 1576–7
ethnic minorities 1585falls 1528–9
group therapy 1366
homicide by 1938

hypomania 1527
illicit drug use 1544indirect self-destructive behaviour 1565
intellectual disability 1584, 1864
carers 1880–1
health needs 1880
life expectancy 1880
with psychiatric/behavioural 
disorders 1858–9

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022elderly people ( cont.)
legal issues 1577–8
life events 1559–60
loss of capacity 1575–8
mania 1527, 1556–7
medication use disorders 1543–5 ,1544
mental health services 1574–5, 1575 ,
1579–86
academic units 1584CARITAS principles 1580community services 1582
comprehensive 1581
consultation-liaison services 1583
core business 1581core components 1581–4, 1582
day hospitals 1583
inpatient units 1582–3
integrated 1581
long-term care 1583
need for 1579–80
patient-centred 1580–1planning to commissioning 1584–5
primary care collaborations 1583–4
principles of good service delivery 1580–1
residential care 1583
respite care 1583
special components 1584
mood disorders 1550–8
neurotic (stress-related) disorder 1558–61
aetiology 1559–60
clinical features 1558
course and prognosis 1560
diagnosis and differential diagnosis 
1558–9
epidemiology 1559
treatment 1560
nicotine use 1544
nutrition 1529obsessive–compulsive disorder 1558
paranoia 1546–50 , 1559

1558–9
parasomnias 1572personality disorders 1561–4
aetiology 1562–3
clinical features 1561–2
course and prognosis 1563
diagnosis 1562epidemiology 1518, 1562–3, 1562
treatment and management 1563–4
pharmacotherapy 1573
physical illness 1559in primary care 1482–3, 1518, 1584
prisoners 1584
psychological treatments 1574
psychoses 1518–19
referral process 1524residential services 1518, 1583
schizoaffective disorder 1552
schizophrenia 1546–50 , 1552
aetiology 1548
classiﬁ  cation 1546–7
clinical features 1546
course and prognosis 1548
diagnosis 1547
differential diagnosis 1547, 1559
epidemiology 1547treatment and management 1548–9
self-esteem 1559
sexuality 1567–70
sleep disorders 1571–3substance use disorders 1519, 1540–6
suicide 976, 1518, 1527, 1551, 1564–7
thought content 1527

treatment, special features 1571–8
electrical allergy 997
electroconvulsive therapy (ECT) 1251–60
in childhood and adolescence 1256
choice of 675in combination with drug therapy 1257
comparison with transcranial magnetic 
stimulation 1264–5
continuation 1257
contraindications 1252, 1252 , 1257
in elderly people 1555, 1556
future of 1258indications 1252–5, 1252
mechanism of action 1257–8
mood disorders 671, 1252–4
origins 1251–2
risks 404, 1257
schizoaffective disorder 598schizophrenia 592
stigma attached 1251, 1258
suggested replacements for 1258
treatment
principles 1256–7process 1256–7
electroencephalography (EEG)
Alzheimer’s disease 337
in antisocial behaviour 1918
Creutzfeldt–Jakob disease 353delirium 328
dementia with Lewy bodies 364

in electroconvulsive therapy 1257
epilepsy 1078, 1862frontotemporal dementias 347
infantile spasms 1862–3
Lennox–Gastaut syndrome 1863
psychogenic seizures 1864schizophrenia 563
sleep stages 925
vascular dementia 380
electromyography, sleep stages 925
electro-oculography, sleep stages 925EMDR see eye movement desensitization and 
reprocessing
emergencies
assessment 68
in childhood and adolescence 1807–11
emergency cards in attempted suicide 970
emergency workers, debrieﬁ  ng 1110
emics 276
emission 817, 822
emotion
anatomy of 257–62
and decision-making 260–1immune modulation 209
and memory 259
and perception 259–60
role of the amygdala 258, 259
emotional development 242–3, 242
emotional lability

in vascular dementia 379emotional learning 258–9
emotional memory 264emotional reasoning 1288
emotional stability 850
emotional withdrawal in depression 634
empathogens 495
empathy 47employee assistance programmes 1281–2
employment
and alcohol use disorders 456
employee assistance programmes 1281–2
supported 1401
empty nest syndrome 1513
encephalitis 1095
herpes 406, 1095
motor sequelae 59
encephalitis lethargica 59
encephalopathy
chronic traumatic 395
early infantile epileptic 1862
early myoclonic epileptic 1862
hepatic 445, 1084–5
mitochondrial 1864, 1865, 1866
ENCODE project 224end-stage renal disease 1087
Endicott Work Productivity Scale 1165
endocannabinoids 168, 172, 429, 429, 507
endophenotypes 266, 652, 1667
endorphins 170, 429, 429
engagement techniques in child and adolescent

engagement techniques in child and adolescent 
engrams 250, 253
enkephalins 429, 429
enmeshment 1371
entactogens 495
entorhinal cortex 146, 152, 180, 251–2, 564, 
1537–8
entrainment test in psychogenic tremor 1016
enuresis, nocturnal 1702
environment
factors in attention-deﬁ  cit hyperactivity 
factors in bipolar disorder 1675
factors in child development 1724–8
factors in conduct disorder 1658–9factors in depression 1675
factors in offending 1913–14
factors in schizophrenia 555–8
host–agent–environment model 1608
interactions with genetic factors 214–18, 
221, 229, 315, 558–9, 1608, 1725
envy 307
ependymal cells 157
Epidemiological Catchment Area study 72, 541, 
645, 1926, 1937
in childhood and adolescence 1594–9
and classiﬁ  cation 1607
contribution to aetiology 280–9
developmental 1607
and ethnicity 277

genetic 286, 650–1, 1597–8
Goldberg–Huxley model 1480, 1481
intergenerational 1598life course 1598
matrix for studies 287, 288
measurement of symptoms 284–6
and prevention science 1598
in primary care 1480–2, 1481 ,1482
in public health 1607–8

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022sampling principles 282–3
specifying disorders 283–4
strategies 286, 287, 288
study design 282
and transcultural psychiatry 14
uses of 280–1
epigenetics 218, 225
epilepsia partialis continua 1531
epilepsia partialis Kojewnikow 1864, 1867
epilepsy 1076–81
absence 204, 1077aetiology 1078, 1619–20
and aggression 1078, 1864, 1929, 1929–30
and Angelman syndrome 1864, 1865and anxiety 1080with attention-deﬁ  cit hyperactivity 
and autism 1852
automatism 403, 1077
benign focal 1618
clinical features 1618–19
course and prognosis 1618–19, 1620
epidemiology 1619with intellectual disability 1861 ,1863 , 1864
classiﬁ  cation 1076–7, 1619, 1862–4, 1863

and crime 1079–80
deﬁ nition 1860–1
and depersonalization 775
and depression 1080
diagnosis 1078, 1619, 1861–2
differential diagnosis 538, 1078, 1619, 
1861–2, 1862
and Down syndrome 1864, 1865
elderly people with intellectual 
disability 1864
epidemiology 1078, 1619
experimental
kindling 204
tetanus toxin model 204
and fragile-X syndrome 1864, 1865
frontal-lobe
behavioural abnormalities associated 1864in childhood and adolescence 1618
and gamma rhythms 203
generalized 1077
genetics 159, 1620
ictus 1077imaging 1078, 1862, 1930
in infancy 1861
and intellectual disability 92, 1828
in adults and elderly people 1864
aetiology and pathogenesis 1865–6, 
1865 ,1866
behavioural disorders 1864
in childhood and adolescence 1863 , 1864
diagnosis 1861–2
differential diagnosis 1861–2, 1863

1865 ,1866
epidemiology 1864–5in infancy 1861, 1862–4, 1863
prognosis 1868
treatment 1866–8, 1867
and memory 92
myoclonic
in childhood and adolescence 1864
in infancy 1863with ragged red ﬁ  bres 1865, 1866
myoclonic–astatic 1863–4
and neuronal networks 201, 203–4
nocturnal seizures 1702
Northern 1864, 1866
and offending 1079–80, 1920, 1929–31
partial 1077and personality disorder 1079
pharmacotherapy 1231–40
in intellectual disability 1866–7, 1867
post-traumatic 394
prodrome 1077
progressive myoclonus 1864
progressive partial 1864
psychiatric consequences 1078–80
psychosis
chronic interictal 1079
postictal 1079
and Rett’s syndrome 1864, 1864–5
and schizophrenia 1079
and sexual function 1079and sleep-wake disorders 932
and social development 1079
and suicide 1080
syndromes 1077–8, 1861

temporal lobe (limbic) 59, 201, 1077
behavioural abnormalities associated 1864
in childhood and adolescence 1618
differential diagnosis 866
effects on learning and memory 204
and personality traits 1930
and transient global amnesia 403
treatment and management 1080, 1620
in tuberous sclerosis 1075
epistasis 229
EPQ-R (Eysenck Personality Questionnaire) 
81, 81, 286, 850
Epstein–Barr virus
and chronic fatigue syndrome 1038and hypersomnia 942
and infectious mononucleosis 1095
Epworth sleepiness scale 938–9
erectile dysfunction (ED) 822
in dementia 416in elderly people 1569
medical intervention 821
pharmacotherapy 821, 828
in physical illness 826
see also  sexual dysfunction
ergot 487
Eriksen Flanker paradigm 265
erotomania 621–2, 1920
error ( e) 85
error catastrophe 1507errorless learning 423–4

ergot 487
escitalopram 670
in obsessive–compulsive disorder 1687in panic disorder 756
ESEMed Study 1433
Esquirol, Jean-Etienne Dominique 18
estavudine 1092
eszopiclone 1102 , 1179, 1182–3
ethambutol 1094
ether 503
ethics and ethical issues 28–32
anorexia nervosa 796
care ethics 31
codes of 30–1
in cognitive-behaviour therapy in childhood 
and adolescence 1778–9
in community mental health services 1457–8
and diagnosis 28–9expert witnesses 2004–5, 2005
factitious disorder 1053–4
malingering 1058
in management 40–1
in management of sexual dysfunction 830
and neurosurgery for mental disorder 
1267–8

1267–8
old age psychiatry 1576–7
in prevention of intellectual disability 1835
principle-based 31
sexual offences 1964
and treatment 29–30and values 32–3
Ethiopia, attitudes to psychiatric disorder 6
ethnic cleansing 1495
ethnic conﬂ  ict 1494
see also  refugees
ethnic minorities
adoption outcomes 1750–1
alcohol use disorders 464
care pathways 1439, 1440–1
caregiver-mediated interventions 1791criminal victimization 1987
culturally informed services for 277
effects of a child with intellectual 
disability 1884
elderly people 1585intellectual disability 1879–80, 1881
mental health services 277, 1502–4
schizophrenia 549, 557–8
voluntary organizations supporting 1491–2
ethnographic database 277
ethnography 275–6, 277
ethosuxumide 1867
etifoxine in adjustment disorders 721
euphoria 55

European Consultation-Liaison Workgroup 
Collaborative Study 1144, 1146
European Convention on Human Rights 1899, 
1900, 1904, 2015
European Declaration for Mental 
Health 1427
evening primrose oil 1249, 1250
event rate 128
event sampling 97
evidence-based medicine 122–8 , 578
appraisal of evidence 126, 126,127
and clinical practice guidelines 123, 124
and current awareness 124–5, 125
evidence hierarchy 123, 1465
ﬁ nding evidence 123–6, 125

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022evidence-based medicine ( cont.)
formulating a structured clinical 
question 122–3
stages 122
and study design 123
and systematic reviews 123–4
types of clinical question 123
use of electronic communication and the 
Internet 124
using research ﬁ  ndings with individual 
patients 126–8
and values-based practice 33
Evidence-Based Mental Health 125, 125
evoked potentials in schizophrenia 563
EWO (education welfare ofﬁ  cer) 1812
exaggeration see malingering
exalted stage 58
excellence, concepts of 43–4, 44
exclusion criteria 100
excoriation, neurotic/psychogenic 
618, 917–18 , 1044
executive control systems 248–9, 248
executive function 262
assessment 89, 90, 265
exercise
and anorexia nervosa 782
in chronic fatigue syndrome 1040, 1042
in dementia 414
in depression in elderly people 1555excessive, in bulimia nervosa 803

exercise
in persistent somatoform pain disorder 1034
exhibitionism 832, 833,836, 1960, 1961
exons 224
expanded trinucleotide repeat sequences 652
experimental event rate 128
expert opinion 75
expert witness 1112, 1901, 2003–8
accreditation 2004
common knowledge rule 2003
and conﬁ  dentiality 2006–7
Court appearance 2007
dual role 2004–5, 2005
ethical issues 2004–5, 2005
immunity from suit 2003
regulatory rules 2004, 2004
reliability 2004
reports 1928, 2004 ,2005–6
and risk assessment 2005
explanation, personal and subpersonal levels 135explanatory gap 135, 278
explanatory models 278
explanatory therapy in hypochondriasis 1026
exposure 55, 1668
in anxiety disorders 1294–5
graded 1779imaginal 742, 746, 1295
in vivo  742, 746
interoceptive 761
in panic disorder 758, 760–1

in post-traumatic stress disorder 708, 1295
social anxiety disorder 742
virtual reality 746
exposure and response prevention in tic 
disorders 1687expressed emotion and schizophrenia 575, 583
expression 213
expressive/exploratory psychotherapy see
psychoanalytic psychotherapy
expressive language disorder 1625–6extinction 250, 254, 1668extradural haemorrhage 387extraversion 81, 81, 632, 633, 654, 850, 886
eye, development 157
eye movement abnormalities in 
schizophrenia 563
eye movement desensitization and reprocessing 
(EMDR) 1497
adjustment disorders 720
in childhood trauma 1730
delusional disorder 1920
following accidents 1109, 1111
post-traumatic stress disorder 709
Eysenck, Hans 1158
Eysenck Personality Questionnaire 81, 81,
286, 850
fabricated or induced illness 1054, 1697, 1737,

286, 850
fabricated or induced illness 1054, 1697, 1737, 
1923–4
facial erythema in alcohol use disorders 446
factitious disorder 994, 1049–54 , 1941
aetiology 1051
classiﬁ  cation 106, 1050
clinical features 1049–50cognitive-behavioural conceptualization 
1051, 1052
course 1051
diagnosis 1050
diagnostic criteria 1049
diagnostic problems 1049
differential diagnosis 1003, 1012, 1012 ,
1050–1
electronic 1050
epidemiology 998, 1051
ethical and legal issues 1053–4
in health care workers 1054induced 1054, 1697, 1737, 1923–4
obstetric 1050, 1118
and pathological lying 1049
prognosis 1051
subtypes 1050and surgery 1096
treatment and management 1052–4
Fahr’s syndrome 373
fail, right to 1408
Fairbairn, W.R.D. 308Faith Links project 1411
falls, elderly people 1528–9
false attribution 1054
false memories 59, 250, 403, 408, 713–16

false-self–real-self distinction 309familial schizotypal disorder 599
familicide 1923
Families and Schools T ogether Track 
programme 1663, 1789
family
assessment 1382–3, 1384–6
and borderline personality disorder 896
burdens on 1401caregiver-mediated interventions 1787–93
changes in patterns of 1726–7
and child physical abuse 1735
and child sexual abuse 1733and conduct disorderfactors in 1659–60
impact of disorder 1655–6
involvement in management 1663
criminal activity by 1659, 1911–12
and cultural variation in care pathways 1439
as decision-makers 1895
disruption 1910–11
effects of alcohol use disorders 452–3, 465
effects of child with intellectual 
disability 1883–6
effects of child with physical illness 1742
effects of childhood and adolescent sleep 
disorders 1694–5

effects of dementia 417–18
effects of Huntington’s disease 374
effects of personality change following head 
injury 391
factors affecting child mental health 1725–7
factors in anorexia nervosa 780
factors in offending 1910–12factors in schizophrenia 536, 548–9, 553–5
in gender identity disorder 844
history 215, 1601
impact of caring on 1465
involvement in management of somatization 
disorder 1009
involvement in rehabilitation of 
delirium 1533
large 1912
nontraditional conﬁ  gurations 1787
reaction to illness 1066
of refugees 1497role in treatment of intellectual 
disability 1873
single-parent 1369–70, 1601, 1726–7, 
1910, 1911
step-families 1370, 1726–7suicide 981–2
Family-Check-Up 1790
family crisis intervention 1382
family focused treatment 1677
family intervention 1401family interview 1386
family life cycle 1373–4

family-mediated interventions see caregiver-
mediated interventions
family myths 1066
family studies 215
anxiety disorders 1667intermittent explosive disorder 912
kleptomania 913
mood disorders 651trichotillomania 915
family support teams 1411
family therapy 1380–91
adjustment disorders 1069
anorexia nervosa 790–2, 790, 796
assessment in 1384–6
in attempted suicide 1707
conduct disorder 1661–2, 1782
conjoint 790–1
contraindications 1383
course 1386
elderly people 1574
historical context 1380–1
indications 1382–3
Milan approach 1381, 1387persistent somatoform pain disorder 1034

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022family therapy ( cont.)
post-modern developments 1381–2
problems encountered in 1388
psychoanalytic and related approaches 1381
psycho-educational approach 1382
research 1388–9
role of the therapist 1386–7schizophrenia 583–4
separated 790–1systems-oriented 1381, 1381–2termination 1387–8
training in 1389–90
transgenerational 1381
family tree 1381, 1384, 1384
famine oedema 785
fantasy (gamma hydroxy butyrate) 409, 498–9
fantasy thinking 50
FAS see foetal alcohol syndrome
FASD (foetal alcohol spectrum disorder) 
1614–15, 1841
FAST (Functional Assessment Staging) scale 
335, 337
‘Fast Track’ programme 1598, 1663, 1789fatigue
differentiation from chronic fatigue 
syndrome 1037
in physical illness 209, 210
as a symptom 1035–6see also  chronic fatigue syndrome
FCU (Family-Check-Up) 1790
fear
pathophysiology 1666–7, 1667
pathways 732
fear conditioning paradigm 1666
‘fear of fatness’ 783
FEAR plan 1779

fear
feeling states, neurobiology of 260–1feelings, deﬁ  nition 260
Feighner criteria 100
Ferenczi, Sandór 1338
fertility and schizophrenia 545
fetishism 833,836
FFT (family focused treatment) 1677
ﬁ broblast growth factor (FGF) 156
ﬁ bromyalgia 990, 997, 1003, 1037
and cortisol 1039
treatment and management 1034
ﬁ ght response following an accident 1107
FII (induced factitious disorder) 1054, 1697, 
1737, 1923–4
ﬁ licide 1125, 1923
Finnish disease heritage 1831
ﬁ re-raising/ﬁ  re-setting see arson; pyromania
ﬁ re sickness ( hwabyung ) 984
5p-syndrome see cri-du-chat syndrome
ﬁ xations 297
ﬂ ashbacks
cannabis 508
in hallucinogen persisting perception 
disorder 488
in post-traumatic stress disorder 404, 701
FLD see frontal lobe degeneration of non-
Alzheimer type
ﬂ esinoxan 735
ﬂ exibilitas cerea 58, 58
ﬂ ight of ideas 53
slow 1527

slow 1527
ﬂ ight response following an accident 1106
ﬂ ooding in panic disorder 761ﬂ oppy infant syndrome 1117
ﬂ uency disorders 53, 1623, 1712
ﬂ umazenil 1172, 1176, 1180
ﬂ unarizine 1201
ﬂ unitrazepam 409, 491, 1178, 1183
ﬂ uoxetine
adverse effects 1173, 1191
in bulimia nervosa 807
and cosmetic psychopharmacology 29
delayed onset of effects 176
in depression 670
continuation treatment 671
in elderly people 1554, 1554
dosage 674, 1196
drug interactions 1233
in obsessive–compulsive disorder 769, 1687
ﬂ upenthixol

in attempted suicide 971
ﬂ uphenazine 1209
administration 1214
adverse effects 1212 , 1222
ﬂ urazepam 1172 , 1179
ﬂ uvoxamine 670
in depression in elderly people 1554
drug interactions 1175
in intellectual disability 1875in obsessive–compulsive disorder 769, 1687
pharmacokinetics 1172 , 1189, 1189
in Wernicke–Korsakoff syndrome 409
fMRI see functional magnetic resonance 
imaging
focal conﬂ  ict theory 1357
focal psychotherapy 1327, 1330–1, 1331
foetal alcohol spectrum disorder 1614–15, 1841
foetal alcohol syndrome (FAS) 445, 1117, 1754
aetiology 1615

imaging
behavioural phenotype 1615classiﬁ  cation 1841
clinical features 1614–15, 1646, 1841
epidemiology 1615
natural history 1615
neurological and behavioural aspects 1841
prevalence 1826, 1841
treatment and management 1615
foetal valproate syndrome 1118
foetus
abuse of 1117adverse environment 659, 1725death in utero  1119
effects of maternal alcohol use see foetal 
alcohol syndrome
effects of maternal substance use 480, 480,
1117–18, 1614, 1615–16
mother–foetus relationship 1117
prenatal diagnosis of intellectual 
disability 1833–4
folic acid deﬁ  ciency 1087–8
folie à deux  610, 624–5
folk healing practices 1418–22
follicle-stimulating hormone in anorexia 
nervosa 783
follow-back studies 556–7, 568
food avoidance emotional disorder 787
food diary 802
food fads 787

food intake history in anorexia nervosa 782
food refusal 787
forced choice testing 94, 1057
forebrain 156–7forensic mental health services 2013, 
2015–21
capacity planning 2017–18
community 1459
international context 2016
philosophy and theoretical models 
2015–16
private 2017
pyramid planning 2017
security 2015, 2016–17
service structure 2017–18
service users 2018–20super-specialist 2017
foresight 80, 80, 82, 83
formal thought disorder 52formulation 68, 73–4
cultural 278
in psychoanalysis 1341–2
fornix 155–6
fortune-telling 1420foscarnet 1091
fosphenytoin in status epilepticus 1867
foster care 1787, 1790, 1800, 1801
forensic/multidimensional treatment 
1790, 1953
long-term 1749–50
short-term 1748–9
treatment 1662
Foulkes, S.H. 1353, 1357

1790, 1953
14-3-3 protein 353
fourth ventricle 157
fragile X-associated tremor ataxia 
syndrome 228
fragile-X syndrome
and autism 1635
behavioural phenotype 1613, 1614, 1840, 
1851 , 1858
effects on the family 1884
genetics 212, 213, 228, 228, 1832, 1839–40, 
1865, 1866
physical characteristics 1840
prevalence 1839–40
psychiatric aspects 1840
fragile-XE syndrome 228
FRAMES 450, 450
framing effect 261

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022France
community mental health teams 1454
and dual-drive theory 302
history of psychiatry 17, 19, 20, 22, 23, 24, 
26, 603, 630, 848
involuntary admission in 1440legal aspects 1901, 1902
prion disease 355, 357
fraud 1941
free association 293–4, 297, 1328, 1770
free-ﬂ  oating discussion 1357, 1360, 1363
free radicals, role in ageing 1509
freeze response following an accident 1106Frégoli syndrome 623
Freud, Anna 310, 1683, 1770
Freud, Sigmund 20–1, 293, 1337, 1770
dual-drive theory 294, 295, 302, 306
models of personality 849
and neurasthenia 1060
and obsessional neurosis 768
and obsessive–compulsive phenomena 1683
and panic disorder 751
and psychodynamic psychiatry 313
and psychosexual development 235
structural theory 294–6
theories on suicide 954
theory of the mental apparatus 293–4
therapeutic technique 1338
topographic theory 294
Freudian slips 313
Friedrich ataxia 228
friendliness 886, 888
FRIENDS programme 1780

Fromm, Eric 311Fromm-Reichmann, Freida 310
frontal eye ﬁ  eld 245
frontal leucotomy 1267frontal lobe degeneration of non-Alzheimer 
type (FLD) 344
aetiology 348
age at onset 345
clinical features 345–6investigations 347
frontal-lobe syndrome 89
frontal lobes
and aggressive/antisocial behaviour 1917–18
anatomy 145–6, 145
association connections 145, 153
lesions 265, 1917–18
frontotemporal lobar degeneration (FTLD) 
344, 344
classiﬁ  cation 344, 344
epidemiology 345
ubiquitinated 344
frotteurism 832, 833,836
FTD see dementia, frontotemporal
FTDP-17 344–5, 346, 348
FTLD see frontotemporal lobar degeneration
fugue states 57, 404–5
functional analysis 96
Functional Assessment Staging scale 335, 337
functional disorders 990

functional family therapy 1661, 1782
functional magnetic resonance imaging (fMRI) 
196–201
alcohol-related dementia 401Alzheimer’s disease 337
anxiety disorders in childhood and 
adolescence 1668
artefacts 197–8
cerebral activation and blood-ﬂ  ow 
changes 197
comparison with PET and SPET 186–7, 
196–7
data analysis 199–201
activation mapping 200, Plate 10
movement estimation and correction 199
multivariate approaches 200
statistical models for the neurovascular 
response 199–200
visualization 201, Plate 11
within- and between-group 200–1
depression 660and emotions 257–8endogenous contrast agents 197epilepsy 1862experimental design 198–9
blocked periodic design 198, 199
event-related design 199
parametric design 199
hardware 198imaging sequences 197
echoplanar imaging 197
gradient echo sequence 197

intermittent explosive disorder 912
in pathological lying 1049, 1051schizophrenia 562–3
functional neuroimaging
alcohol-related brain damage 401
anorexia nervosa 781attention-deﬁ  cit hyperactivity disorder 1647
conversion disorder 1013
and emotion 257–8, 260, 261
epilepsy 1078, 1079
post-traumatic stress disorder 706–7schizophrenia 562–3
with violence 1919
see also speciﬁ  c techniques
functionalism 134
challenges to 134–5
fusion of thought 53
G (gamma hydroxy butyrate) 409, 498–9
G protein-coupled receptors 172, 173, 174, 175,
202, 1171
regulation 175
G-proteins 174–5, 473, 1201‘G spot’ 818
G72 gene 555
GABA 148, 155, 429
and body dysmorphic disorder 1046
effects of valproate on 1231
and epilepsy 1619, 1865
hippocampus 202
in opioid neurobiology 473in panic disorder 754

and schizophrenia 562
transporters 169, 170
GABA receptors 1171
action of benzodiazepines at 1171, 1179in generalized anxiety disorder 733, 734
hippocampal 202ligand-gated ion channels 173, 174gabapentin 1237
Gabitril (tiagabine) 1237, 1867
gaboxadol 1183
GAD see generalized anxiety disorder
GAF (Global Assessment of Functioning 
scale) 73, 1165, 1593
gait abnormalities 57
galanin 171, 171
receptors 173
galantamine
in Alzheimer’s disease 409, 1241
Gamblers Anonymous 922, 1352
gambling, pathological 919–23
aetiology 920–1
classiﬁ  cation 920
clinical features 920course and prognosis 922
diagnosis 920
epidemiology 920–1

impulsive 920
neurotic 920
predisposing factors 921–2
prevention 923psychopathic 920
subcultural 920
symptomatic 920
treatment and management 922
γ-aminobutyric acid see GABA
gamma butyl-lactone 498
gamma hydroxy butyrate 409, 498–9
γ-linolenic acid 1248, 1249
gamma rhythms 203
ganciclovir 1092ganoderic acid 1063
Ganoderma lucidum  1063
Ganser syndrome 1049, 1055
Gastaut–Geschwind syndrome 1930
gastroesophageal reﬂ  ux 932, 1084
gastrointestinal disorders 1083–4
in rapid refeeding 786
Gaucher disease type 3 1865
GBH (gamma hydroxy butyrate) 409, 498–9
GBL (gamma butyl-lactone) 498
GDS see Geriatric Depression Scale; Global 
Deterioration Scale
Gedankenlautwerden  49
gender
and anorexia nervosa 778
and anxiety disorders 1666
and attention-deﬁ  cit hyperactivity

gender
disorder 1646, 1828
and autism 1828and body dysmorphic disorder 1045
and childhood OCD and tics 1681
and conduct disorder 1655, 1658
and deliberate self-harm 959
by elderly people 1565
and hypochondriasis 997
and mood disorders 271, 648, 653–4and offending 1909
and prevalence of somatization 
disorders 996
and psychiatric disorder in intellectual 
disability 1828

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022and schizophrenia 544–5
and social anxiety disorder 741
and speciﬁ  c phobia 745
gender identity 57gender identity disorder 57, 106, 842–6
childhood and adolescence 1718–23
assessment 1721clinical features 1718–19
epidemiology 1718
longitudinal studies 1720–1
and mental disorder 1721
treatment 1721–2
diagnosis 842
epidemiology 842
and homosexuality 1720
legal issues 845
origins 842–3
patient subgroups 844
Real Life Experience 843, 844
treatment and management 843–4
validity 845
General Health Questionnaire 69, 283, 284
general hospitals
liaison visits to 1525
organization of psychiatric services 1144–8
‘general neurotic syndrome’ 682
general paresis (of the insane) 1093
general practitioners (GPs)
ability to detect psychiatric morbidity 1482
education regarding suicide risks 974
expectations of psychiatrists 1486–7
training in psychiatry 1487–8

generalizability theory 92generalized anxiety disorder (GAD) 729–39
aetiology 732–5, 732,733,734
in childhood and adolescence 1664
clinical presentation 1665
outcome 1666prevalence 1666
clinical features 729
comorbidity 731, 731, 736
course and prognosis 735and depression 731
diagnosis 729–30, 730
differential diagnosis 730–1, 730, 741, 752, 
1004, 1024
epidemiology 731following stroke 1071
genetics 732
and life events 735
treatment and management 735–7validity of disorder 731
vulnerability to 734–5
generation 1513
genetic counselling 1281
Alzheimer’s disease 340
dementia 411
Huntington’s disease 374–5
in intellectual disability 1825, 1884
genetic epidemiology 286, 650–1, 1597–8genetic tagging 231
genetic testing
dementia 411, 412

genetics
and ageing 1507–8analysis methods 216–17
candidate genes 220–1, 651
components of phenotypic variation 214
continuous traits 213, 213
and epidemiology 286, 650–1, 1597–8
functional analysis 230–2
gene association studies 220–1, 220, 226–7, 
230, 651
gene copy-number variants 230
gene–environment correlation 214
gene–environment interactions (GXE) 
214–18, 221, 229, 315, 558–9, 1608, 1725
gene expression control errors 1508
gene expression regulation 218, 223–6, 224
gene interactions (epistasis) 229
gene mapping 218, 226–7
gene mutations 1508, 1831–2
Mendelian 227–9
mis-sense 227
non-sense 227
point 227–8
and psychiatric disorders 227–9, 228
triplet repeats 228, 228
genome organization 223
genotyping 226
and intellectual disability 1831–2, 1831 , 1838

with behavioural/psychiatric disorder 1858
and life expectancy 1507linkage analysis 218–20, 218, 227, 230, 651
markers 218, 226
Mendel’s laws 212
model ﬁ  tting 217
molecular 222–33 , 286
multiple regression analysis 217
neurodevelopmental disorders 159
non-additive genetic effects 214
nucleic acid structure and function 223path analysis 217, 217
patterns of inheritance 212–13, 213
and personality traits 886–8, 888–9, 890
polymorphism 218
psychiatric–behavioural 1597–8psychiatric disorders
in childhood and adolescence 1590
complex 229–30
Mendelian/single-gene 212–13, 213, 
227–9, 228
quantitative 212–22
research methods 215–16
whole genome association (WGA) 
studies 221, 229–30
alcohol use disorders 434–6
Alzheimer’s disease 227, 339, 1521

227–9, 228
Angelman syndrome 213, 224, 229, 1841, 
1865, 1866
disorder 1590, 1646
autism 1635–6
body dysmorphic disorder 1046
chronic fatigue syndrome 1038
Cofﬁ  n–Lowry syndrome 1842
conduct disorder 1658
cri-du-chat syndrome 1842
de Lange syndrome 1842delusional disorder 614
dementia with Lewy bodies 365Down syndrome 228, 1831, 1838–9Duchenne muscular dystrophy 1843
eating disorders 781–2, 806
epilepsy 159, 1620
fragile-X syndrome 212, 213, 228, 228,
1832, 1839–40, 1865, 1866
frontotemporal dementias 348
generalized anxiety disorder 732
Huntington’s disease 372
hypochondriasis 1024
Klinefelter syndrome 1840
Lesch–Nyhan syndrome 1843mood disorders 648, 650–8 , 658
mucopolysaccharidoses 1843
neuroﬁ  bromatosis type 1 1843, 1866

obsessive–compulsive disorder 768, 1684
offending 1918
panic disorder 753–4
phenylketonuria 212, 214, 1844post-traumatic stress disorder 707
Prader–Willi syndrome 213, 224, 229, 1844
Rett’s syndrome 224, 229, 1637, 1844, 1866
Rubinstein–Taybi syndrome 1845
schizophrenia 547, 548–9, 553–5, 
565–6, 565
Smith–Lemli–Opitz syndrome 1845
Smith–Magenis syndrome 1845
smoking addiction/nicotine 
dependence 510–11
substance use disorders 428–9
suicide 954–5, 966–7
tic disorders 229, 1073, 1684
tuberous sclerosis 1075, 1845, 1866
Turner syndrome 224, 1840
velo-cardio-facial syndrome 1846
Williams syndrome 1846
X-linked intellectual disability 1839
XXX syndrome 1841XYY syndrome 1841
genital herpes 1094
genital-retraction anxiety disorder ( koro) 606, 
779, 979, 980–1
genogram 1381, 1384, 1384

genotype 212, 226
gentamicin 1091
geophagia 1116gepirone 735
Geriatric Depression Scale 719, 1551, 1552
German chamomile 1248
Gerstmann–Straussler(–Scheinker) 
syndrome 351, 356–7
Gestalt therapy 1277
gestational substance use 480, 480, 1117–18, 
1614, 1615–16, 1754
GHB (gamma hydroxy butyrate) 409, 498–9
GHQ (General Health Questionnaire) 
69, 283, 284
GHQ-12 284
GHRF (growth hormone-releasing factor) 
165, 171
Gillick Rules 1899Ginkgo biloba
adverse effects 1248
as cognitive enhancer 1247–8
drug interactions 1250
ginseng see Panax ginseng
GIPs (GPCR-interacting proteins) 175give way weakness in conversion disorder 1016

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022Glasgow Coma Scale 388, 388
glioblasts 157
gliosis in schizophrenia 180–1, 180, 181
Global Assessment of Functioning scale 
73, 1165, 1593
global burden of disease 645
alcohol use disorders 10, 467
mental disorder 10–11, 1428, 1606
in childhood and adolescence 1595–6
mood disorders 645, 1185smoking 510
Global Deterioration Scale 1535
globus pallidus 154, 155, 1684
glove and stocking anaesthesia 57glutamate 429
ligand-gated ion channels 172, 173, 174
in obsessive–compulsive disorder 1684
in opioid neurobiology 473
role in neurodevelopment 159and schizophrenia 562
transporters 170, 170
glutamate receptors, hippocampal 202
Glyccirhiza glabra  1249
Glycine max  1249
glycine receptors 1171glycine transporters 169–70, 170
glycosylation (glycation) of proteins 1508–9
GNP and population mental well-being 1428
GnRH (gonadotrophin-releasing 
hormone) 162, 165

GnRH analogs in the paraphilias 838
Go-No-Go tasks 266
gonadotrophin-releasing hormone 162, 165
good-enough mother 309goserelin 1964
GPCR-interacting proteins 175
GPCR kinases 175
GPs see general practitioners
graded activity in adjustment disorders 1069
Graded Naming T est 89, 266
graduate mental health workers 1485
grandiose delusions 51
grandparenting
effects of a grandchild with intellectual 
roles 1514
transition to 1513–14
green (ketamine) 489, 499–500 , 1186
grief
after diagnosis of intellectual disability in a 
child 1883
after infant loss 725, 1119–20assessment and management 726–7
counselling in 726–7, 1279
normal 725
traumatic 725, 1985
see also  bereavement
Grifﬁ  ths Developmental Scale 1821
grimacing 58
grooming 1961, 1962

normal 725
gross national product and population mental 
well-being 1428
group-analytic group therapy 1351, 1353, 1355, 
1357–8, 1357 ,1358
group-as-a-whole 1353
group homes 1454group matching 1468
group therapy 1350–69
activity 1351–2
antisocial personality disorder 898
basic methods 1351–3
bipolar disorder 673borderline personality disorder 895, 1364–5boundary events 1363
brief 1366
childhood and adolescence 1768
chronic mental disorder 1364
cognitive-behavioural 742, 744
curative factors 1355, 1356
domestic violence perpetrators 1982–3
elderly people 1366fostering therapeutic norms 1363
group-analytic 1351, 1353, 1355, 1357–8, 
1357 ,1358
group development theory 1358–60
historical aspects 1353–4
homogeneous/heterogeneous groups 1362
hypochondriasis 1027interpersonal 1351, 1355, 1356
intervention guidelines 1363, 1363
language of the group 1360

leadership 1350–1, 1360–2
multiple family 1382, 1389with offenders/prisoners 1365
optimal/sub-optimal size 1363
organizing principles 1353
outpatient 1364, 1365
in the paraphilias 838, 839in physical illness 1364
problem-solving 1351, 1352
psychoanalytic 1351
psychodynamic 1352–3, 1354–8
psychoeducational 1351, 1352, 1364research and evaluation 1366
schizophrenia 1364
selection and composition 1362, 1362
service planning 1366–7
setting 1364short-term dynamic 1351
smoking cessation 512
supportive 1352
systems-centred 1351
Tavistock 1351, 1355–7, 1356
therapeutic goals 1350, 1351
therapist 1354, 1354
with trauma victims 1365
‘growing pains’ 1695
growth
arrested in anorexia nervosa 787
drug-induced retardation 1795
growth hormone 164–5
and sleep 1695

growth
growth hormone-inhibiting hormone 165growth hormone-releasing factor 165, 171
GSS (Gerstmann–Straussler–Scheinker 
syndrome) 351, 356–7
guanfacine 1651, 1688
guanine 223
guanylate cyclase 176
guardianship 29–30, 1895, 1898
guided imagery and recovered memories 715
Guillain–Barré syndrome 942
guilt
delusions of 51and depression 634
unconscious 294
gynaecological conditions 1114–16
HAART in HIV-associated dementia 385
habit reversal
in tic disorders 1687
Hachinski Ischaemia Score 379, 379
HADS (Hospital Anxiety and Depression 
Scale) 1486
haematological disorders 1087–8
haemodialysis 1087, 1139haemoglobin 197
Halban’s fascia 818
halitosis, delusions of 618–19
Hallowell, Irving 276hallucinations 49
aetiological theories 50
after infant loss 1120in alcohol withdrawal 443, 538

associated with simple partial seizures 1864
auditory 49
cognitive-behaviour therapy 1314, 1317
therapy 1265
bodily/tactile/coenaesthetic 50
in delusional disorder 609, 610, 613, 615
in dementia with Lewy bodies 335, 361
and depression 641differential diagnosis of cause 537
and disinhibition 50
gustatory 50hypnagogic 50, 940, 1702
hypnopompic 940, 1702
olfactory 50
and overstimulation 50in Parkinson’s disease 1072
phencyclidine-induced 487
in schizophrenia 527, 573–4
somatic 1030
visual 49–50
hallucinogen persisting perception 
disorder 488–9
hallucinogenic mushrooms 488
hallucinogens 487–9
acute effects 488

adverse effects 488–9
botanical 488
epidemiology of abuse 488
human experimentation with 489
preparations 488
hallucinosis, alcoholic 443, 538
haloperidol 1209, 1209
administration 1213, 1214
in autism 1875

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022in dementia 414
pharmacodynamics 1211 , 1212
in postoperative delirium 1099
in schizophrenia 586
Hamilton Anxiety Rating Scale 1164
Hamilton’s Rating Scale for Depression 69, 70, 
634, 1163, 1164
hand use preference and gender identity 
handicap
adjustment to 1065–71
HapMap (International Haplotype Map) 
222, 227
‘happy puppet’ syndrome see Angelman 
syndrome
Hardy–Weinberg equilibrium 213, 226
Hare Psychopathy Checklist 835
harm-avoidance 79–80, 80, 316, 316, 849
‘harmful dysfunction’ concept 28
harmine 501Harvard Trauma Questionnaire 1497
hashish see cannabis
hate crimes 1987
Hayling T est 90
HCR-20 (Historical Clinical Risk-20) 1927, 
1994, 1997, 1998, 2018
head-banging 1601
head injury 387–99
agitation and aggression following 
393, 396, 1929

and alcohol use disorders 393–4
amnesia following 404, 407
and boxing 395and capacity 397
in childhood and adolescence 394–5, 1616–18
closed 387–8, 394, 1617
cognitive impairment following 390–1, 395
and delusional disorder 614and depression 92
differential diagnosis 695
early symptoms 392
epidemiology 388–9
epilepsy following 394as form of torture 1495
function and health 389
immediate response to 1107
and insight 397
investigations 389late effects 388
long-term outcome 389–90
loss of consciousness 388malingering following 1055
management of sequelae 395–7
mood disorders following 393, 396
neuropathology 387–8, 387
and offending 1920open 387, 394, 1617
personality change following 391
post-concussion syndrome 394, 395–6, 1929

psychological sequelae 390
psychosis following 392–3recovery from 389–90refugees 1495
severity 388, 388
and sleep-wake disorders 932, 942, 1698
Head Start programme 1788
headache
in childhood and adolescence 1745
induction by transcranial magnetic 
health
behavioural factors inﬂ
 uencing 1135–7
beliefs 1136–7
deﬁ nition 1606
and lifestyle 1136
and personality 1136
and stress 1135–6
Health and Education for Life Project 1814–15
Health Anxiety Inventory 1023
Health Belief Model 1137, 1140
health care behaviour 1138–40health care services
high users 1137–8
types 44–5
health care workers
alcohol use disorders 457
assaults on 1986
factitious disorder 1054
Health Maintenance Organization 45
Health of the Nation Outcome Scale 70, 73health promotion

types 44–5
in childhood and adolescence 1610
comparison with prevention 1609
see also  prevention, primary
health psychology 1135–43
behavioural factors inﬂ  uencing health 
1135–7
health care behaviour 1138–40
symptoms and illness behaviour 1137–8
treatment behaviour 1140–2
health-related behaviour 1136–7
health-risk behaviours 1136
Health T echnology Appraisals 124
health visitors 1486
Healthy Start programme 1788hearing, cortical association pathways 147, 152
heavy metal exposure 1825
Helicobacter pylori  1084
Heller’s syndrome 1637
HELP (Health and Education for Life 
Project) 1814–15
help-seeking behaviour
and culture 15, 1441–2
delay in 1137
hemisensory syndrome 1017hemispherectomy 1867
hepatic encephalopathy 445, 1084–5
hepatitis B infection
and hypersomnia 942

and opioid use 475and substance use disorders 430
hepatitis C infection
and opioid use 475
and substance use disorders 430
hepatocerebral degeneration 445
hepatolenticular degeneration 537, 1084
heritability 214
broad-sense 214
narrow-sense 214
heroin 430, 473, 515action at opioid receptors 473
administration routes 473
brown 473complications of use 474–5, 475
dependence 474
assessment 478
in childhood and adolescence 480
conﬁ  rmation of 478
management 477–9
outcome 481treatment 475, 476–8, 479, 1242–7
detection 473
epidemiology of use 474
metabolism 473–4, 474
overdose 474–5, 479, 480
in pregnancy and breastfeeding 480, 480,
1615–16
prescription 476
tolerance 473, 474, 478withdrawal 474
measurement 478, 478
see also  opioids; substance use disorders
herpes
encephalitis 406, 1095

1615–16
herpes
genital 1094
heterozygosity 212, 226
5-HIAA see 5-hydroxyindoleacetic acid
hierarchy of evidence 123, 1465
highly active antiretroviral therapy in HIV-
associated dementia 385
hindbrain 156, 157
hippocampal formation 148, 149, 182, 202, 
251–2, 252, 733
hippocampus 158, 159, 251
anatomy of neuronal network 202–3, 202
cortical projections to 155–6
emergent properties of networks 203
in epilepsy 203–4
evoked responses 202
and fear/anxiety 1666–7, 1667
lesions 252, 252
local circuits 202
and long-term potentiation 251, 251
and memory 204, 251–3, 251, 259
rhythms 203in schizophrenia 179–80, 179
structure and organization 146, 148, 149
HIS syndrome 1909histaminergic system 151, 1210, 1211
histones 223, 225
historical background
Alzheimer’s disease 334
anorexia nervosa 777art therapy 1414

biological and psychological model of mental 
disorder 19–20
bipolar disorder 631community care 24
depression 629–31
diagnostic systems 631
family therapy 1380–1
hypochondriasis 1021–2mental health social work 1408
mood disorders 629–31
neuropsychiatry 20
neuroses 20–1
neurosurgery for mental disorder 1266–7
pharmacotherapy 25psychiatry as a medical specialty 17–27

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022historical background ( cont.)
psychiatry as profession 18
psychoanalysis 23, 1338–9
psychodynamic psychiatry 23
psychotherapies 20–1schizophrenia 521–6
sexual dysfunction 821–2social aspects of psychiatry 18–19
Historical Clinical Risk-20 1927, 1994, 1997, 
1998, 2018
histrionic personality disorder 868–70
aetiology 869
classiﬁ  cation 856,869
clinical features 869–70
comorbidity 870, 884
course and prognosis 870
diagnosis 869–70
differential diagnosis 866, 870, 874
in elderly people 1562, 1562 , 1563
epidemiology 869, 882, 883
treatment 870
HIV/AIDS 1091–3
acute stress reaction in 1091counselling in 1280–1
delirium in 1092–3, 1093
delusions of 619
dementia in 384–6 , 1091
depression in 1092effects on family members 1742
interpersonal psychotherapy (IPT-HIV) 
1092, 1322
mania in 1092
nature of neuropsychiatric disorders in 1091and opioid use 475
opportunistic CNS infections 1093

1092, 1322
parental, effects on child development 1755
prevention 1447
psychosis in 1092and stigma 1091
and syphilis 1093
HLA typing in sleep-wake disorders 930
HMO (Health Maintenance Organization) 45home treatment programmes for 
schizophrenia 584
home visitation programme 1788, 1789
homelessness 1500–2
and alcohol use disorders 456, 464barriers to care 1500–1
deﬁ nition 1500
demography 1500
and psychiatric disorder 1500
service organization and delivery 1501
homicide 1937–40
altruistic 1923
by children/adolescents 1952–3by elderly people 1938
by spouse/partner 1981
and delusional disorders 1920
female perpetrators 1938
general population 1937infant 1119, 1125, 1937–8
longitudinal trends 1939–40
mass 606, 979, 981, 1938
methods 1937
multiple 1938perpetrators with mental health service 
contact 1938–9

perpetrators with schizophrenia 1939, 1995and personality disorder 1921
risk assessment 1939–40
secondary victims 1985
serial 1938
‘stranger’ 1937
and substance use disorders 1926suicide following 1923, 1938
Homicide Act 1957 1901
homosexuality 832
and gender identity disorder 1720
and hate crimes 1987
homozygosity 212, 226
honesty-humility 850
Hong Kong
attitudes to psychiatric disorder 6neurasthenia 1061
HONOS (Health of the Nation Outcome 
Scale) 73
Hoover’s sign 1016
Hopelessness Scale 1165
Hopkins Symptom Checklist 284, 1497
Hopkins Verbal Learning T est 253hops 1248
Horney, Karen 310–11Hospital Anxiety and Depression Scale 1486
hospitals
counselling in 1280–1
schools 1815
see also  day hospitals; general hospitals; 
secure hospitals
hostels 1454

hospitals
housing, supported 1400
HOX genes 1614HPA axis see hypothalamic–pituitary–adrenal 
(HPA) axis
HPCL (Hare Psychopathy Checklist) 835
HPPD (hallucinogen persisting perception 
disorder) 488–9
5-HT and 5-HT receptors see serotonergic 
system and serotonin receptors
5-HT
1A partial agonists 1181
see also  buspirone
HTAs (Health T echnology Appraisals) 124
Hughlings-Jackson, J. 523
Human Genome Project 218, 222, 1510
human rights
European Convention on Human 
Rights 1899, 1900, 1904, 2015
Human Rights Act 1998 2015
and mental health public policy 1427
and refugees 1493UN Declaration of Human Rights 1427, 1494
violations of 11
Humulus lupulus  1248
Hunter syndrome 1843
huntingtin gene  372
Huntington disease-like 2 228, 373
Huntington’s disease 212, 213, 228, 228, 371–5
and aggression 1929
in childhood and adolescence 372–3

clinical features and course 371–2
diagnosis 372–3
differential diagnosis 348, 373–4
genetics 372
pathology 372
risk of 374–5
subcortical triad of symptoms 369
treatment and management 374
Hurler syndrome 1843hwabyung  984
HY antigen 842hydergine
as cognitive enhancer 1248
hydrocephalus following head injury 388
hydrocortisol in acute stress reactions 697
5-hydroxyindoleacetic acid (5-HIAA)
in borderline personality disorder 867
and intermittent explosive disorder 912
and repetitive self-mutilation 917
and suicide 964, 965
hyperactivity
and offending 1909see also  attention-deﬁ  cit hyperactivity 
disorder
hyperactivity–impulsivity–attention deﬁ  cit 
syndrome 1909
hyperarousal following an accident 1107
hypercalcaemia 1085–6

disorder
hypercarotenaemia in anorexia nervosa 785
hypercortisolaemia in depression 660–1, 
1252, 1258
hyperdopaminergia 562
hyperemesis gravidarum 1116
hyperforin 1249
hyperglycinaemia 1863
hypergraphia 1079Hypericum perforatum  (St John’s wort) 386, 
686, 1248, 1250 , 1262
hyperkinetic disorder see attention-deﬁ  cit 
hyperactivity disorder
hyperkinetic stereotyped movement 
disorder 1633
hyperkinetic syndrome 1654, 1657
see also  attention-deﬁ  cit hyperactivity 
disorder
hypernomia 850hyperparathyroidism 1085–6
hyperphagia with seasonal affective 
disorder 1260
hyperprolactinaemia 815, 826, 1086, 1217, 1223
hyperreﬂ  exia in HIV-associated dementia 384
hypersalivation, drug-induced 1223
hyperschemazia 57
hypersexuality
in childhood and adolescence 1671
in Huntington’s disease 373

hypersomnia 927, 928,938–43 , 1083, 
aetiology 939–43
assessment 938–9
of central origin 940–2
epidemiology 938
idiopathic 941–2
morbidity 938
with physical illness 942post-traumatic 942
recurrent 942
with seasonal affective disorder 1260
with sleep-related breathing disorder 939–40
substance-induced 939treatment 939–43
hypertension 1081
hyperthermia and ecstasy 495hyperthymia 690–1

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022hyperthyroidism 1085
panic-like symptoms 752
hyperventilation
in chronic fatigue syndrome 1038following an accident 1106
hypnogram 925, 925, 930
hypnosis
in conversion disorder 1019in persistent somatoform pain disorder 1034
in post-traumatic stress disorder 709
and recovered memories 715
hypnotics 1178, 1179
abuse 1183
adverse effects 1183
clinical effects 1182–3dependence 1183
half-lives 1183
rebound 1183
residual effects 1183
hypocalcaemia 1085
hypochloraemia in bulimia nervosa 804
hypochondriacal delusions 51
hypochondriasis 57, 1021–9
aetiology and pathogenesis 1025–6
assessment instruments 1023, 1023
and chronic fatigue syndrome 1037classiﬁ  cation 993–4, 993, 994, 1022–3, 1022
clinical features 1022, 1022
cognitive and perceptual factors 1025
comorbidity 1024, 1027
complications 1026conceptualizations 1022
controversial aspects 997

correlates and risk factors 997, 1024
course 1026
deﬁ nitions 996
developmental factors 1025
differential diagnosis 1003, 1023
epidemiology 996–7, 998, 1024–5
family studies 1024
and functional symptoms 992
history of disorder 1021–2
interpersonal factors 1025
and life events 1025monosymptomatic 997–8
morbidity 1024–5
and pain 1031
and personality 1025
phenomenology 996prevalence 996–7, 998, 1024
prognosis 1026
and service utilization 1024–5
and sexually transmitted diseases 1094
social and cultural factors 1025–6and somatic delusional disorder 617–18
subtypes 1022
treatment and management 1026–8, 
1027 , 1034
twin studies 1024validity of diagnosis 1023
hypocretin 930, 941
hypofrontality in schizophrenia 188–9, 562
hypoglycaemia in anorexia nervosa 785
hypogonadism 826, 828, 834hypokalaemia in bulimia nervosa 804
hypomania 631

in Alzheimer’s disease 335and attempted suicide 1704
clinical features 635, 635
differential diagnosis 644, 870
duration 646
elderly people 1527see also  cyclothymia/cyclothymic disorder
Hypomania Checklist 635
hypomobility 58
hyponatraemia
in anorexia nervosa 794
in bulimia nervosa 804
hyponomia 850hypoparathyroidism 1085
hypophosphataemia in rapid refeeding 786
hypopituitarism 781, 1086
hyposchemazia 57
hypotension
and chronic fatigue syndrome 1038drug-induced 1190, 1223, 1529in frontotemporal dementias 346
hypothalamic–growth hormone axis 164–5
hypothalamic–pituitary–adrenal (HPA) 
axis 164–5
and avoidance response 658
and birth weight 659
effects of stress on 206–7in generalized anxiety disorder 732

axis 164–5
hypothalamic–pituitary–gonadal axis 165
in anorexia nervosa 781, 783–4
hypothalamic–pituitary–thyroid axis 163
hypothalamic–prolactin axis 165–6
hypothalamotomy 1267hypothalamus
and circadian rhythms 1260
components of the hypothalamic–pituitary–
end-organ axes 162–3, 162
feeding centre 781
hypothermia in anorexia nervosa 785
hypothyroidism 163, 1085
congenital 1616
physical and cognitive 
characteristics 1842
prevalence 1825–6, 1842
in Down syndrome 1839
hypoxia, amnesia following 406–7
hysterectomy 1116
hysteria 57, 1021
see also  conversion disorder
hysterical blindness 1017
ibogaine 488, 1249, 1250
IBS (irritable bowel syndrome) 997, 1003,

IBS (irritable bowel syndrome) 997, 1003, 
1037, 1083
ICD see entries under International Classiﬁ  cation 
of Diseases
ice (methamphetamine) 497–8
‘ice-pick’ lobotomy 1267
ICER (incremental cost-effectiveness 
ratio) 124, 1475, 1475
ICESCR (International Covenant on Economic 
Social and Cultural Rights) 1427ICF ( International Classiﬁ  cation of Functioning, 
Disability and Health ) 65, 389, 1399, 
1820–1, 1821
ICIDH ( International Classiﬁ  cation 
of Impairments, Disabilities and 
Handicaps ) 65, 389, 1399, 1820
ICM (intensive case management) 1402
ICPC-2-R (International Classiﬁ  cation for 
ICSD-2 (International Classiﬁ  cation of Sleep 
Disorders) 927, 928, 933, 934, 938, 
1695, 1698
ICU (intensive care units) 1139id 294–5, 306, 313, 849
id resistances 297
ideal object 308

1695, 1698
ideal types 849idebenone 1240identity, disorder of awareness of 56
identity theft 1970identity theory 134
idiopathic CNS hypersomnia 1701
idiopathic infantile hypercalcaemia see Williams 
syndrome
IDO (indoleamine 2,3 dioxygenase) 209
IED (intermittent explosive disorder) 911–13
Ifa 1420
IGFs (insulin-growth factors) 206
IL-1 (interleukin-1) 209illness
cognitive models 1138
concept of 62, 63–4, 277–8
coping with 1066deﬁ nition 989
as a demand/threat 1066
division into ‘medical’ and ‘psychiatric’ 989
interpersonal basis of experience 277
perceptions 1138
phobia of 52, 1022, 1023resources for response to 1066
self-regulatory model 1138
as a stress 1065
see also  mental disorder; physical illness; 
terminal illness
Illness Attitude Scales 1023
illness behaviour and somatization 
disorder 1003, 1009

illness deception model 1051
illness delay 1137illness self-management in 
schizophrenia 583
illusions 49, 1030
iloperidone 1209administration 1220–1
ILPs (independent learning plans) 1716
imagery 49, 1779
in insomnia 937
imagery modiﬁ  cation 1292–3
images, negative 1288
imipramine 670, 1185

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022immune system 205–11
effects of echinacea 1249
effects of stress 205, 207, 1135–6
modulation of emotion and mood 209
neural inﬂ  uences 206–7
receptors 206as sensory organ 207, 209
Impact of Event scale 703impact rule 1902impairment 389
imprinting 213, 224–5
defects 229
Improvement Foundation 1488
impulse control disorders 911–19
in bulimia nervosa 803deﬁ nitions 911
and offending 1924
impulse control enhancement 1771–2
impulsivity 850
and offending 1909
imu 983
in vitro  fertilization (IVF) 1115
and intellectual disability 1883
inappropriate affect in schizophrenia 529
incidence 281, 1607
secular changes in 280–1
inclusion criteria 100
Incredible Years, The  1788
incremental cost-effectiveness ratio 
indeloxazine 1240
independent learning plans 1716
India
Action for Mental Illness 1491

India
attitudes to psychiatric disorder 6cost of psychiatric disorder 11
traditional medicine 1061
indigenous folk healing practices 1418–22
indoleamine 2,3 dioxygenase 209infancy
caregiver-mediated interventions 1787–8
death in 1119
epilepsy with intellectual disability 1861, 
1862–4, 1863
maternal anxieties about infant health and 
survival 1121–2
mother–infant relationship disorders 1123–4
psychoanalytic theories of sexuality 294–5
relinquishment in 1120
sleeplessness in 1698
see also  childhood and adolescence
infanticide 1119, 1125, 1937–8infantile spasms 1618, 1862–3, 1867
infection 1090–5
and chronic fatigue syndrome 1038–9
and obsessive–compulsive disorder 1685opportunistic in HIV/AIDS 1093
pharmacotherapy 1091, 1091

prenatal exposure to, and schizophrenia 
547–8, 556
and tic disorders 1073, 1685
see also speciﬁ  c infections
infectious mononucleosis 1095inferior frontal gyrus 245inferior parietal lobe 245
inferior temporal sulcus 146inferotemporal cortex 146, 148infertility 1114–15
see also  fertility
inﬂ ammatory bowel disease 1083–4
inﬂ uenza, prenatal exposure to 547–8
analysis and integration 65
categories 63
condensation and recording 73–4
effects on stigma 5–6
keeping up to date with 122–9
objective 63
scientiﬁ  c 63
subjective 63
information-giving in counselling 1275–6
information variance 284informed consent 29, 1895
for neurosurgery for mental disorder 1267–8
in psychiatric emergencies in childhood and 
adolescence 1811
for psychotherapy in childhood and 
adolescence 1765
for surgical procedures 1096–7

inhalant abuse see volatile substance abuse
inheritance
multifactorial 213
patterns of 212–14, 213
polygenic 213
inhibition, sexual 825
injury see accidents; head injury; sleep-related 
injury
Injury Severity Score 1105
inositol 176
inositol triphosphate 174, 176
inpatient care
in alcohol use disorders 449, 455–6, 461anorexia nervosa 792–3, 793, 794–5
in community mental health services 1452–3
containment of violent behaviour 1404
diagnosis-speciﬁ  c 1453
for elderly people 1582–3global survey 12, 12
health psychology of 1139–40
and psychiatric nursing 1404
stress associated 1139–40
and suicide 1404
insanity defence 1900–1, 1922–3, 1923, 1928
insight 56, 80, 80, 83
in body dysmorphic disorder 1044
following head injury 397
measurement 56in psychoanalysis 1340
in schizophrenia 528

insistence on sameness in autism 1633
insomnia 927, 928,933–8 , 1182
aetiology 934–5
childhood-onset/idiopathic 1699
classiﬁ  cation 933
clinical features 933
course and prognosis 935
and depression 934
diagnosis 934differential diagnosis 934
epidemiology 934
fatal familial 352
prevention 937
rebound 935treatment and management 935–7institutional racism 276
institutionalization 236–7, 1393, 1396insula 145, 148, 152, 260insulin-growth factors 206insulinoma 1101integration 1278
intellect/imagination 850
intellectual disability 1861
in adults 1884
aetiology 1821–2, 1830–7
assessment 1833–4, 1833
central nervous system 
malformations 1832
classiﬁ  cation of causes 1830, 1831
complexity of causes 1830
external prenatal factors 1832
genetic factors 1831–2, 1831 , 1838
importance of conﬁ  rmation of 1834

paranatally-acquired disorders 1832
postnatally-acquired disorders 1833
untraceable/unclassiﬁ  ed 1833
and aggression 1855–6, 1929
anger management 1874
and anxiety disorders 1855
and art therapy 1414–15
assessment 1821–3
disorder 1850–1, 1876
and autism 1852, 1855
behavioural programmes 1874
and bereavement 1881and bipolar disorder 1827, 1854–5
characterization 1821–2
prevalence 1878
psychiatric and behaviour disorders 
associated 1849–53 , 1879
classiﬁ  cation 54, 86, 1592, 1593 , 1819–21, 
1820 ,1821
cognitive-behaviour therapy 1874

1820 ,1821
communication skills 1873and conduct disorder 1657, 1851
and consent to sexual activity 1900
and culture 1879–80, 1881deﬁ nitions 1825
and deinstitutionalization 1881, 1887, 1890
and deliberate self-harm 1856
and dementia 1827, 1828, 1855
and depression 1827, 1852, 1854–5diagnosis 1833–4, 1833
multiaxial 1871–2
differential diagnosis
antisocial personality disorder 866
pervasive developmental disorders 1639speciﬁ  c developmental disorders 1623
and dysthymia/dysthymic disorder 1855
and education 1873, 1884
effects on the family 1883–6
elderly people 1584, 1864
health needs 1880life expectancy 1880

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022with psychiatric/behavioural disorders 
1858–9
and epilepsy 92, 1828
1865 ,1866
epidemiology 1864–5in infancy 1861–2, 1862–4, 1863
ethnic minorities 1879–80, 1881
health inequalities 1819
and IQ 1820, 1825mental state examination 1823
needs assessment 1823–4
normalization 1872
and offending 1856
and oppositional-deﬁ  ant disorder 1851
and paraphilias 834
and parenthood 1885
and personality disorders 1856pharmacotherapy 1875–6
prevalence 1825–6
prevention 1447–8, 1448
coordinated 1835
ethical issues 1835primary 1834
secondary 1834–5
tertiary 1835
psychiatric and behaviour disorders in 
adults 1854–60
aetiology 1857–8
assessment 1822–3, 1856
and baseline exaggeration 1854
classiﬁ  cation 1857

clinical features 1854–6and cognitive disintegration 1854
and deprivation 1828
diagnosis 1822–3, 1856–7
in elderly people 1858–9
epidemiology 1826–7, 1827 , 1857
and intellectual distortion 1854
and levels of support 1828
and life events 1828
mental health service planning and 
provision 1887–92
outcome measurement 1889
and physical illness 1828
protective and vulnerability factors 1827–8
and psychological masking 1854
residential programmes 1889
and smoking 1828
stafﬁ ng and training 1889–90
vocational programmes 1889
childhood and adolescence 1849–53
assessment 1822–3
classiﬁ  cation 1849–50
diagnosis 1822–3, 1849–50
management principles 1852–3
and physical illness 1850
social and family inﬂ  uences 1850

psychodynamic psychotherapy 1874–5and psychoses 1826, 1827, 1854
rational emotive therapy 1874
and schizophrenia 1827, 1854self-help skills 1873
and sexual relationships 1873, 1879
and sleep-wake disorders 926–7, 1694, 
1697–8
and social inclusion 1819
and social relationships 1873social role valorization (SRV) 
approach 1409–10
spectrum of 1819
difﬁ culty 1712
and stereotypic movement disorder 
1683, 1851
and sterilization 1116
syndromes 1838–48
therapeutic communities 1397
and tic disorders 1851
treatment 1871–7
methods 1873–6
therapeutic environment 1872–3
United Nations Declaration on the Rights of 
Mentally Retarded Persons 1895–6
X-linked 1831–2, 1839–40, 1842
see also speciﬁ  c disorders and syndromes
intellectual openness 886

intellectual performance disorders 54
intellectualization 294
intelligence
assessment and measurement 22, 54, 87, 88,
263–4
conceptualization 54, 263–4
and offending 1909–10
premorbid 90, 90, 264, 548
intelligence quotient see IQ
intensive care units 1139
intensive case management 1402
intention-to-treat analysis 128, 142, 1155
intentional communities 1392interactive techniques in child and adolescent 
interferon 1091
interleukin-1 209
INTERMED-method 1145, 1146
intermetamorphosis 623
intermittent explosive disorder 911–13
internal consistency of a test 85
international agencies and mental health public 
policy 1427
International Bill of Rights 1427
International Classiﬁ  cation of Diseases, 
development and early editions 100–2
ICD-9 100, 631

neurasthenia 1060personality disorders 856
ICD-10 108–13 , 631
acute stress reactions 693, 694, 694
adjustment disorders 717, 1066–7
Alzheimer’s disease 336
Asperger’s syndrome 1638, 1638
autism 1633–4, 1634
categorical approach 849in childhood and adolescence 1592–3childhood disintegrative disorder 1637as classiﬁ  cation of disorders 64
Clinical Descriptions and Diagnostic 
Guidelines  (Blue Book) 103
comparison with DSM-IV 102–4
conduct disorder 1656, 1657
cyclothymic disorder 686
delirium 327, 1531
delusional disorder 103–4, 609, 613, 613
depression 633, 633, 639
development 100–2

Diagnostic Criteria for Research  (Green 
Book) 103
eating disorder 787, 800–1
frontotemporal dementias 348generalized anxiety disorder 730, 730
hyperkinetic disorder 1643
impulse control disorders 911
with psychiatric disorder 1826, 1849–50
malingering 1054mania 635, 635
multiaxial version 73, 103
neurasthenia 1062
obsessive–compulsive disorder 1682
panic disorder 751–2pathological gambling 920
personality disorders 852, 852, 855–7, 856
disorder 874
paranoid personality disorder 861

pervasive developmental disorders 1623, 
1633, 1639
701, 702–3 , 703
Primary Health Care  version (PHC) 103
Rett’s syndrome 1636, 1636
schizoaffective disorder 598
schizophrenia 103–4, 534, 534,536, 541, 569, 
571, 1547
Short Glossary of ICD-10  103
somatoform disorders 104, 993, 994, 1003
conversion disorder 1012
hypochondriasis 997, 1022–3persistent somatoform pain disorder 997, 
1029–30
somatization disorder 
996, 999–1000, 1003
speciﬁ  c developmental disorders 
1623, 1623 , 1627
structure 102–4
vascular dementia 377–8, 377

ICD-10-PHC 1483–4

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022International Classiﬁ  cation of Diseases, ICD-11, 
research planning for 106–8
International Classiﬁ  cation of Functioning, 
Disability and Health  65, 389, 1399, 
International Classiﬁ  cation of Impairments, 
Disabilities and Handicaps  65, 389, 
1399, 1820
International Classiﬁ  cation for Primary 
Care 1484
International Classiﬁ  cation of Sleep Disorders 
927, 928, 933, 934, 938, 1695, 1698
International Covenant on Economic, Social 
and Cultural Rights 1427
International Covenant on Political and Civil 
Rights 1427
International Haplotype Map 222, 227
International Initiative for Mental Health 
Leaders 1488
Examination 72, 858, 859
International Pilot Study of Schizophrenia 
14, 71, 523, 527, 528, 540–1, 541, 572, 574
International Study of Schizophrenia 572–3, 
572, 574
Internet
counselling services based on 109, 1814–15
and suicide pacts 1706
use in evidence-based medicine 124

572, 574
Internet
interneuronal network gamma 203
interpersonal and social rhythm therapy 647, 
673, 1319, 1323
interpersonal counselling 1324interpersonal development 1600–1
interpersonal group therapy 1351, 1355, 1356
interpersonal inventory 1320
interpersonal psychoanalysis 310
interpersonal psychotherapy (IPT) 
1278, 1318–26
adjustment disorders 1068, 1069
anorexia nervosa 792
anxiety disorders 1324
avoidant personality disorder 897background 1319
bipolar disorder 1323
bulimia nervosa 808, 809, 1323–4by telephone 1324
comparison with other psychotherapies 
1321, 1333–4, 1333
contraindications 1319
conversion disorder 1019depression 672–3, 676, 1322–3
1322, 1676
in elderly people 1555
maintenance treatment 1322–3
and marital conﬂ  ict 1322
peripartum 1322
in primary care 1322

1322, 1676
dysthymia/dysthymic disorder 686, 1323
in HIV/AIDS 1092, 1322
indications 1319phases of treatment 1319–20
predictors of response to 1324
research 1324
substance use disorders 1324techniques 1320–1
training in 1325
interpersonal relation phobia 982interpersonal skills training in conduct 
disorder 1662
interpretationism 134–5
interpreters
mental health professionals as 67use in assessment 67
interval scales 86
interventricular foramen 157
interviewing, privacy of 67
intracerebral haemorrhage 387introjection 294
introjective type 316introns 224introversion 81, 632, 633, 635, 654, 850, 
862, 878
intrusion following an accident 1107
intuition, delusional 51
invasion of privacy in diagnosis of factitious 
disorder 1053
Inventory of Depressive Symptomatology 1163
Inventory of Interpersonal Problems 1165

iodine deﬁ  ciency 1448, 1825
Iowa Gambling Task 265
Iowa Strengthening Families program 1790IP
3 (inositol triphosphate) 174
IPC (interpersonal counselling) 1324
IPDE (International Personality Disorder 
Examination) 72, 858, 859
iproniazid 1185, 1190
ipsapirone in generalized anxiety disorder 735IPSRT (interpersonal and social rhythm 
therapy) 647, 673, 1319, 1323
IPT see interpersonal psychotherapy
IPT-HIV 1092, 1322
IQ 54, 263–4
classiﬁ  cation 86
difference scores 86, 86
and intellectual disability 1820, 1825
population distribution 1825premorbid, strategies for estimation 90, 90
scores 86
tests 67, 88
z-scores and percentiles 86
Irish Affected Sib Pair Study 435iron deﬁ  ciency 932, 1088
irresponsibility in elderly people 1561
irritable bowel syndrome 997, 1003, 1037, 1083

scores 86
irritable heart syndrome 751
Islamic communities, attitudes to psychiatric 
disorder 7
isocarboxazid 670, 670
adverse effects 1190, 1191 , 1193
limitations on use 1187
isolation 294
isoniazid
in tuberculosis 1094
isoproterenol 754
isoxsuprine 1240
ISS (Injury Severity Score) 1105ITT (intention-to-treat analysis) 128, 142, 1155
IVF see in vitro  fertilization
Janet, Pierre 20, 21
Japan
attitudes to psychiatric disorder 7life expectancy 1507
neurasthenia 1061
jargon aphasia 54Jaspers, Karl 523
jealousy 619–20
cognitive therapy 1920
delusional 51, 619–21, 1920, 1967
pathological 51, 620–1, 862, 1920, 1998
jet (ketamine) 489, 499–500 , 1186
jet lag 1261
journals
systematic reviews in 1156

journals
judgement 80, 80, 83
‘Just Say No’ campaign 1598
juvenile delinquency 1654, 1945–59
disorder 1948–9
and depression 1949and early-onset psychosis 1950
epidemiology 1945
legal issues 1954–5
and mental disorder 1946–7, 1948–50, 
1951–2
K (ketamine) 489, 499–500 , 1186
Kahlbaum, Karl 521
kainate receptors 172, 173, 1171
kava 1248, 1250
Kendra’s Law 2015
Keppra see levetiracetam
Kernberg, Otto 311
ketamine 489, 499–500 , 1186
ketoconazole 1091

kidney, transplantation 1087
kissing 815
Klein, Melanie 306–7, 308, 1770Kleine–Levin syndrome 942, 1701
kleptomania 913–14 , 1924, 1942–3
Klinefelter syndrome 834
behavioural and psychiatric aspects 1840
genetics 1840
prevalence 1840
Klüver-Bucy syndrome 258–9, 346
knockout/knock-in technology 230, 231
Kohlberg, Lawrence 235
Kohut, Heinz 311
koro 606, 779, 979, 980–1
Korsakoff syndrome see Wernicke–Korsakoff 
syndrome
Kraepelin, Emil 522, 531, 540, 568, 603, 609, 
610, 630, 681
kudzu 1249
kujibiki  1420
kuru 351, 354–5
‘la belle indifference’ 1016

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022LAAM 1243–4
labelling 5
labia 817
lacunar state 377
Lafora disease 1864, 1866
Laing, R.D. 24, 309
lamina terminalis 157lamotrigine 1198, 1200, 1235
adverse effects 1200 , 1204, 1235
in bipolar disorder 671, 677in childhood and adolescence 1798in cyclothymia/cyclothymic disorder 689
in depersonalization disorder 775
dosage and administration 
1233 , 1235, 1236
drug interactions 1206, 1232, 1235, 1866
indications and contraindications 1235
overdose 1235
pharmacokinetics 1203, 1235, 1867
pharmacology 1235in pregnancy 1235
withdrawal 1206–7, 1235
Landau–Kleffner syndrome 1618, 1626–7, 
1640, 1712, 1864
language see speech and language development; 
speech and language disorder/difﬁ  culty
lanti  984
lasting power of attorney 1577
latah  606, 983
late paraphrenia 1547

lanti  984
lateral horn 157lateral ventricles 157, 159
laurasidone 1209
Lavandula angustifolia  (lavender) 1248
law and psychiatry see legal issues
laxative abuse
in anorexia nervosa 783, 784, 794
learned helplessness 684, 1982
learning, in epilepsy 204
learning disability see intellectual disability
learning disorders 1623, 1623 , 1627–31
learning mentors 1812
legal issues
action-taking 1895–900
anorexia nervosa 796arson 1966
decision-making 1895–900
gender identity disorder 845
juvenile delinquency 1954–5law relating to people with mental 
disorder 1895–907
old age psychiatry 1577–8
paraphilias 834responsibility 1900–5
sleep–wake disorders 948–9
substance use disorders 1927–8
Leibniz, Gottfried 133

lemon balm 1248Lennox–Gastaut syndrome 1618, 1862, 1863Lesch–Nyhan syndromebehavioural and psychiatric aspects 
1838, 1843
behavioural phenotype 1613, 1614
physical characteristics 1843
prevalence 1843
Letter–Number Span 255
leuprolide acetate 1964
Level of Service Inventory, Revised 2011
levetiracetam 1237
levodopa
adverse effects 730
in dementia with Lewy bodies 366
Lewis, David 134
Lewy bodies 361
composition 362
cortical 362in Parkinson’s disease 361, 369
sites 362
subcortical 362
Lewy body disease see dementia, with Lewy 
bodies
Lewy neurites 362
in Parkinson’s disease 369lexipafant 386
liability
for clinical negligence 1902criminal 1900–1
of mentally ill people in negligence 1903–4
to mentally ill people who self-harm 1905

liability
of providers of mental health services 
1904–5
for psychiatric injury 1902–3
to third parties for acts by mentally ill 
people 1904
tortious 1901–5
vicarious 1904–5
liaison, in consultation-liaison psychiatry 1145
libidinal object 308
libido 294, 295
and castration 815–16
in epilepsy 1079postnatal loss 1121
reduced/low 822
management 828
LIFE (Longitudinal Interval Follow-up 
Evaluation) 1165
life course 1512
perspective 1513–14
structuring through age 1512–13
life events
and aetiological models 269–71
and anorexia nervosa 779–80in clinical assessment 66–7
and conversion disorder 1014
and depression 269–73, 270,271, 648, 659
effects on children and adolescents 1601
elderly people 1559–60and exposure to adversity 286
and generalized anxiety disorder 735

and hypochondriasis 1025and immune function 207
involving danger 270
involving entrapment 270
involving humiliation 270
involving loss 270and mania 647
and mood disorders 269–73, 270,271, 659
and schizophrenia 558, 575and suicide 954, 969, 1705
Life Events and Difﬁ  culties Schedule 67, 
269–71
life expectancy
and ageing 1507, 1509–10
healthy 1509–10
and population ageing 1579
life skills training see social skills training
life stories 1514–15
life table analysis 215
life transitions 1513–14lifechart 67, 73
lifestyle
and ageing 1507
LIFT (Linking the Interests of Families and 
T eachers) programme 1789
light box 1261
light visors 1261
limbic cortex 150, 152–3, 1267

limbic leucotomy 1267limbic-lobe syndrome 866
lingzhi  1063
linkage disequilibrium 220, 221, 651
Linking the Interests of Families and T eachers 
programme 1789
lipid metabolism disorders 1084
lipofuscin 1508liquid ecstasy (gamma hydroxy butyrate) 
409, 498–9
liquorice 1249
LIS1 protein 158
literature searches 123
lithium 1198, 1198–208
adverse effects 1200 , 1204
hypothyroidism 1085
risk factors 1175
teratogenicity 1169–70
in attempted suicide 971, 1707
in bipolar disorder 671, 677
in body dysmorphic disorder 1047and breast-feeding 1169–70
depression 1677
psychiatric/behaviour disorder and 
comparison of immediate-release and

comparison of immediate-release and 
modiﬁ  ed-release 1169, 1169
in cyclothymia/cyclothymic disorder 689
drug interactions 1175, 1205in elderly people 1556
historical perspective 1200
indications and contraindications 1205in intellectual disability 1875
maintenance treatment 671
monitoring therapy 1176in personality disorders 906

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022lithium ( cont.)
pharmacodynamics 1172
pharmacokinetics 1170, 1172 , 1202–3
pharmacology 1201, 1202 ,1203
in pregnancy 677, 1118, 1205
psychoprophylactic use 1448
and surgery 1097
withdrawal 1206
litigation
following accidents 1111–12
and malingering 1057
vexatious see querulous behaviour
liver
effects of alcohol use disorders 445, 446, 456
transplantation 456
local worlds 277
locus coeruleus 151
LOD score 219, 222
lofepramine 670
lofexidine 477, 1245
Logical Memory test 264
logistic regression 141
logoclonia 53
logorrhoea 53long-term plasticity 251
long-term potentiation 202, 231, 251, 251
longevity
and need for mental health services 1579–80
and rate of living 1508variance in 1507
Longitudinal Interval Follow-up 
Evaluation 1165
loosening of association 53, 528

longevity
Lophophora williamsii  488
loprazolam 1179
lorazepam 1178
in adjustment disorders 721
adverse effects 1180
in alcohol withdrawal 1542in cancer 1102 ,1104
dosage 1180
indications 1178in panic disorder 756, 757
pharmacokinetics 1172 , 1178
love, delusions of 51
love maps 813, 837
loxapine 1209
adverse effects 1212
LSD 487
differential diagnosis of intoxication 487
epidemiology of use 488
psychosis induced by 489, 538use in pregnancy 1117LSI-R (Level of Service Inventory, Revised) 2011
LTP (long-term potentiation) 202, 231, 251, 251
LTPP (long-term psychodynamic psychotherapy) 
318–19, 1327, 1329, 1338, 1345

Lunacy Act 1845 19luteinizing hormone in anorexia nervosa 783
lying 1941
pathological 54, 871, 1049, 1051, 1941
Lyme disease 1094–5
Lyrica (pregabalin) 743, 1182, 1237lysergic acid diethylamide see LSD
MacArthur Risk Assessment Study 1937
machine functionalism 134
McNaghten rules 1900–1, 1928
MACT (manual-assisted cognitive 
treatment) 895
made acts 527
Madrid Declaration 40, 40–1
magersucht  783
magic-fear-induced death 981magnetic resonance imaging see functional 
magnetic resonance imaging; structural 
magnetic resonance imaging
magnetic resonance spectroscopy 186
epilepsy 1862
lithium therapy 1202mood disorders in childhood and 
adolescence 1674
magnetization 191, 192
magnetoencephalography in epilepsy 1862
maintenance of wakefulness test 939make-belief 1941
Malan, David 310
malaria 1447
malarial fever therapy 1251

mali-mali  983
malingering 57, 994, 1049, 1054–8 , 1096, 1941
aetiology 1057
assessment instruments 1057
classiﬁ  cation 1056
clinical features 1055–6and cognitive assessment 91
and cognitive deﬁ  cit 1055–6
course 1057
deﬁ nition 1054
diagnosis 1056
1051, 1056
epidemiology 1054–5
ethical and legal issues 1058
following accidents 1111
partial 1054
and physical disease 1056and post-traumatic stress disorder 1055
prevention 1058
prognosis 1057
and psychoses 1055
pure 1054symptom validity tests 1057
treatment and management 1057–8
malnutrition
in alcohol use disorders 445
in anorexia nervosa 784–6
managed care 45
management 39–46
activities 41
basic concepts 40categories 41deﬁ nition 40

ethical aspects 40–1functions 40information systems 42levels and styles 42quality 43–4, 44
risk 44
roles and responsibility of managers of 
clinical units 42
and strategic planning 43
management by objectives 43
management science 42
mania
assessment 1675
childhood and adolescence 1670–1, 
1675, 1677
clinical features 635–6, 635
cultural inﬂ  uences 14
and Cushing’s syndrome 1086
differential diagnosis 644, 870, 1531
and Down syndrome 1826
duration and severity of episodes 635–6
elderly people 1527, 1556–7
endophenotype 266following head injury 393
and life events 647
and physical illness 1132
postpartum 647
with psychotic features 636

risk factors 646–7and sleep-wake disorders 931
stages of 636
treatment 677–8, 1253–4
unipolar 633
without psychotic features 635–6
mania à potu  60
Mania Rating Scale 1675
manic episode disorder 633
mannerisms 58, 58
manual-assisted cognitive treatment 895MAO-A see monoamine oxidase-A
MAOIs see monoamine oxidase inhibitors
Map Search 88, 89
maple syrup urine disease 1863
maprotiline 669
Marchiafava–Bignami syndrome 445
marijuana see cannabis
marital conﬂ  ict
and depression 1753
effects on child mental health 1726
interpersonal psychotherapy (IPT-CM) 1322
and mood disorders 653and offending 1910–11
marital status, and depression 648
marital therapy see couple therapy

Maroteaux-Lamy syndrome 1843
marriage 1369–70
consanguineous 1825

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022and culture 1370
masochism 832–3, 833,836, 877, 878
masochistic personality disorder 877–8
massacre, autogenic (self-generated) 1938
MAST-G 1519
masturbation
degeneration theory 836
surveys of 813–14
‘matchbox’ sign 618
matching 1468
maternal deprivation 285maternity blues 1121
mathematics disorder 1630
mating behaviour 815
Matricaria recutita  1248
MATRICS battery 263, 265
Matrix Model 1463, 1464 , 1889
Mayo Fluctuations Composite Scale 363
MBDB ( N-methyl-1-(1,3-benzodioxol-5-yl)-
2-butanamine) 494
MBO (management by objectives) 43
MBT (mentalization-based therapy) 
304, 894, 1341
MCI see mild cognitive impairment
MCMI (Millon Clinical Multiaxial 
Inventory) 858, 858, 1962
MDA (methylenedioxyamphetamine) 494MDAS (Memorial Delirium Rating Scale) 328
MDEA (methylenedioxyethylamphetamine) 
494
MDMA see ecstasy
MDT (mode deactivation therapy) 1953MEsee chronic fatigue syndrome
Mead, Margaret 276
mean 86

494
mean 86
mean green (ketamine) 489, 499–500 , 1186
Measure of Parenting Style 286measurement scales 85–6
MECA (Methods for the Epidemiology of 
Child and Adolescent Mental Disorders) 
study 1594
media, exposure to in childhood and 
adolescence 1601
medial temporal lobe
and declarative/episodic memory 251–3, 252
in mild cognitive impairment 1537–8
median 86medical anthropology 276
medical practice models 64
medical pupil referral units 1815
Medical Research Council see MRC
medical sociology 268–75
context and measurement 268
life events and building aetiological models 
269–73
methodological considerations 269
medical students’ disease 1137Medical Symptom Validity T est 1057
medication use disorders in elderly 
people 1543–5 ,1544
meditation 1418
medroxyprogesterone acetate 838, 1964meiosis 223
melancholia 681, 1021
features 640–1

treatment 1252–3
melanocortin agonists in sexual 
dysfunction 828
MELAS (mitochondrial encephalopathy with 
lactic acidosis and strokes) 1865, 1866melatonin 925, 935, 1183, 1248, 1250 , 1262
melatonin receptor agonists in insomnia 935
Melissa ofﬁ  cinalis  1248
memantine
in Alzheimer’s disease 1241
in HIV-associated dementia 385
Memorial Delirium Rating Scale 328
memory
in anxiety disorders 1288
assessment 89, 89, 253, 254, 255–6, 264, 
420–1, 420
biographical 59cellular and molecular mechanisms 251, 251
classiﬁ  cation 250–1, 250
declarative (explicit) 59, 250, 313
assessment and neuropsychology 253
neural system 251–3, 252
delusional 51, 59, 611
development 241–2, 241–2
distortion following head injury 392effects of benzodiazepines 1179

emotional 264
encoding 264
enhancement 396–7
and epilepsy 92, 204episodic 241, 250, 264, 407, 1179, 1761
and emotions 259
neural system 251–3, 252, 259
eye witness 241–2
false 59, 250, 403, 408, 713–16
immaturity in childhood 1761
long-term (remote/secondary) 59, 250, 407
remediation 421–4, 422
and mood disorders 59
non-declarative (implicit) 241, 250, 313, 407
assessment and neuropsychology 254
neural systems 254
preverbal (eidetic) 1761
procedural 59, 250, 254, 313–14
prospective 407in psychiatric practice 249–50
psychology and biology 249–57
rate of forgetting 253
recognition 241, 264
recovered 714–15, 834remediation and rehabilitation 421–4, 422
repression 293–4, 314
retrieval 264
role of amygdala 264

semantic 250, 264, 406, 407short-term/recent 59, 250, 264, 407
visual 247–8
situationally accessible 696
ultrashort-term (sensoric/echoic/iconic) 
59, 250
verbally accessible 696
working/primary 242, 250, 264, 407
assessment and neuropsychology 255–6
neural systems 254–5
remediation 421
and schizophrenia 255
memory aids
assessment of use 420, 421
electronic 423
memory clinics 1584memory impairment, age-associated (AAMI) 
1535, 1535–6
see also  amnesia
memory strategy training 423
Mendel, Gregor 212
meningitis
and chronic fatigue syndrome 1038cryptococcal 1093
tuberculous 1094
menopause 823
menstrual cycle and sexual behaviour 816
menstruation 1114
and anorexia nervosa 782, 783, 787
Mental Capacity Act 2005 1897, 1898–9
mental causation 134
Mental Deﬁ  ciency Act 1913 1819

disease burden 10–11, 467, 1428, 1606
and juvenile delinquency 1946–7, 1948–50
interventions 1951–2
myth of 28
and offending 1917–26 , 2009–10
1752–4, 1755–6
phenomena of 47
prevalence in the community 1480
prevalence in general hospital 
population 1144
prevalence in primary care 1480–2, 1481 ,1482
prisoners 1933–6
scope of term 1933
and violence 1937
as worldwide public health issue 10–13
mental health, deﬁ  nition 1606–7
Mental Health Act 1930 22
Mental Health Act 1959 1898
Mental Health Act 1983 1491, 1905
Mental Health Alliance 1491mental health budgets, global survey 11, 11
mental health legislation, global surveys 11, 11
mental health literacy 5
mental health nurses see psychiatric nurses

mental health professionals
burnout 1449, 1449
engagement in risk assessment 1993–4
global survey 11, 12
as interpreters 67perceptions of need 1433
in primary care 1485–6
recruitment 1429
role in primary prevention 1449–50, 1450
stalking of 1972working with people with intellectual 
disability and psychiatric 
disorder 1889–90
see also speciﬁ  c professions
mental health public policy 1425–31
comparative 1426–7
deﬁ nitions 1425
and economic impact of disease 
burden 1428
and equitable resource allocation 1430function 1426
and funding 1429–30
global surveys 11, 11
and human resources 1429and human rights 1427

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022mental health public policy ( cont.)
implementation 1428–9
and international agencies 1427
need for 1427–8
positive and negative drivers 1425–6
scope of development 1428
mental health resources
allocation 1473equitable allocation and mental health public 
policy 1430
global 11–12
insufﬁ  ciency 1473–4
for adults with intellectual disability 
1887–92
for alcohol use disorders 459–67
assessment of utilization 1165
for bipolar disorder 646child and adolescent (CAMHS) 1802–7 , 1946
accessibility 1805–6
client groups 1803
cost-effectiveness analysis 1476–7
evidence-based development 1804
inclusion of schools 1811–12
inclusion of speech and language 
therapists 1716
multi-disciplinary teams 1812
prioritizing need 1803–4
provision of interventions 1804–5
quality 1806referrals to 1811
role in medico-legal assessment 1954–5
role in special education 1815
service structure 1805stafﬁ ng 1805

community 1452–62
acute beds 1452–3
community mental health centres 1454community mental health teams 584, 
1454–5, 1456 ,1457 , 1458, 1888–9
crisis teams 1458, 1458
day care 1453development principles 1461
diagnosis-speciﬁ  c teams 1459
for elderly people 1582
ethical aspects 1457–8forensic teams 1459
inpatient beds 1452–3
monitoring and review 1460
and needs of offenders/prisoners 1934
ofﬁ ce-based care 1454
outpatient clinics 1454
planning 1459–60
rehabilitation in 389–90, 1459
residential care 1453–4
supported accommodation 1453–4
culturally competent 1502–4, 1503
dangerous and severe personality disorder 
(DSPD) services 2015, 2018
economic analysis 1473–9
examples 1476–7, 1478

macro-level 1473–4, 1473
micro-level 1474–6
for elderly people 1574–5, 1575 ,1579–86
academic units 1584CARITAS principles 1580
community services 1582
inpatient units 1583
long-term care 1583need for 1579–80patient-centred 1580–1
planning to commissioning 1584–5
for ethnic minorities 277, 1502–4
evaluation 1463–72
deﬁ nitions and conceptual 
framework 1463
key challenges 1470
Matrix model 1463, 1464
outcome measures 1464–5, 1464
purpose of 1463, 1464
research design 1465–9, 1465 ,1466 ,1467 ,
1468 ,1469
ﬁ nancing 11, 11
forensic 2013, 2015–21

1468 ,1469
international context 2016philosophy and theoretical models 
2015–16
security 2015, 2016–17service structure 2017–18
service users 2018–20
super-specialist 2017
global improvement 12–13
for homeless people 1501, 1501
integrated 990, 1460
liability of providers 1904–5
for mothers 1124–5
needs see needs
for offenders 1934–5
forensic 1459, 2013, 2015–21
general psychiatric services 2009–14
needs 1934–5
provision in prisons 1934–5
organization in general hospital 
departments 1144–8
for personality disorder 907
primary care 1486
research on 281, 1452
for schizophrenia 584–5
for substance use disorders 515–20
see also  consultation-liaison (CL) psychiatry
mental health social work 1408–13
behavioural 1409
care management 1410–11

crisis approach 1409
historical development 1408
innovative practice 1411
legal and policy framework 1410–11
problem-solving approach 1409
psychodynamic approaches 1408–9social dimension 1409social role valorization (SRV) approach 
1409–10
strengths model 1410
task-centred 1409values underpinning 1408
mental hygiene 22
mental retardation see intellectual disability
mental status examination (MSE)
in childhood and adolescence 1601, 1602
in intellectual disability 1823see also  Mini-Mental State Examination
Mental Status Schedule 71
mentalization 1948
mentalization-based therapy 304, 894, 1341
meprobamate 1178
MeRAs (melatonin receptor agonists) in 
insomnia 935
mescaline 488
mesencephalon 156, 157mesoridazine 1209

meta-analysis 229, 1155, 1465–6, 1466
metabolic disorders 1084–5
metabolic enhancers 1240
metachromatic leukodystrophy 537meta-communications 1381
metencephalon 157
meth (methamphetamine) 497–8
methadone 475, 1243
action at opioid receptors 473detoxiﬁ  cation 477
injectable 476
metabolism 473
in pregnancy 1118, 1615–16prescription 479
methamphetamine 497–8
Methods for the Epidemiology of Child and 
Adolescent Mental Disorders study 1594
methohexitone 117818-methoxycoronaridine 1249
N-methyl-1-(1,3-benzodioxol-5-yl)-
2-butanamine 494
methylenedioxyamphetamine 494methylenedioxyethylamphetamine 494
3,4-methylenedioxymethamphetamine 
see ecstasy
methylphenidate 1795
abuse potential 1795adverse effects 1650, 1795
1241, 1648, 1650, 1876

in HIV-associated dementia 386
in intellectual disability 1876in narcolepsy with cataplexy 941
rebound effects 1795
metoclopramide 1101Mexico, attitudes to psychiatric disorder 6
Meyer, Adolf 22
MFQ (Mood and Feelings 
Questionnaire) 1675, 1780
MFTG (multiple family group therapy) 
1382, 1389

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022mianserin 670, 671
adverse effects 1191, 1191
pharmacodynamics 1173 ,1187 , 1188
midazolam 1104
midbrain 156, 157
‘midweek blues’ 495
migraine
and depersonalization 775and transient global amnesia 403
migration and schizophrenia 286, 549, 557–8mild cognitive disorder 1534
mild cognitive impairment (MCI) 266, 1519, 
1534–9 , 1574
aetiology 1537, 1537
amnestic 1520, 1535
assessment 1536
biomarkers 1537–8
clinical staging scales 1535
cognitive assessment 1536
deﬁ nition 1520, 1534
diagnosis 1536–8, 1537
diagnostic criteria 1535
epidemiology 1535–6, 1536
mortality risk 1536
neuroimaging 1537–8neuropsychiatric symptoms 1537
nosology 1534–5, 1534
progression to dementia 1535–6reversion to normal 1536
treatment and management 1538
vascular 407
mild neurocognitive disorder 1534
millenniary delusions 982Millon Clinical Multiaxial Inventory 
858, 858, 1962

milnacipran
pharmacokinetics 1188, 1189
mind–body dualism 133, 989–91
mind–body literature 205
mind–brain relation 133–6
mindfulness-based cognitive therapy 1310
mindfulness skills in body dysmorphic 
mini-ethnography 278
‘minimal brain dysfunction’ 1631, 1643
Mini-Mental State Examination (MMSE) 
87, 284
in Alzheimer’s disease 337, 1240
in delirium in elderly people 1531
with elderly people 1527, 1528
extended 1527, 1528
in mild cognitive impairment 1536
sensitivity to education 284
in vascular dementia 380
Minnesota Multiphasic Personality Index
use in malingering 1057
use with sex offenders 1962
‘miracle question’ 1276
mirror retraining in body dysmorphic 

mirror sign 334mirror therapy in adjustment disorders 720mirroring 311, 1357
mirtazapine 670, 671
adverse effects 1191, 
1191 , 1555
miscarriage 1119
misidentiﬁ  cation, delusional 51, 392, 609–10, 
611, 622, 623–4
misidentiﬁ  cation syndromes
delusional 51, 392, 609–10, 611, 622, 623–4
and risk of violence 1998
mission statement 43
Misuse of Drugs Act 1971 1927
Mitchell, Stephen 311
mitochondria 223
and ageing 1508
mitochondrial disorders 1832
mitochondrial encephalopathy with lactic 
acidosis and strokes 1865, 1866
mitochondrial encephalopathy with ragged red 
ﬁ bres 1864
mitral valve prolapse 752

ﬁ bres 1864
mixed anxiety-depressive disorder 718–19
MMSE see Mini-Mental State Examination
mobile phones, counselling services 
using 1814–15
MoCA (Montreal Cognitive Assessment) 1536
moclobemide 670, 670
pharmacodynamics 1172, 1187 , 1188
modaﬁ  nil
disorder 1241, 1651
in hypersomnia 939in narcolepsy with cataplexy 941
mode 86
mode deactivation therapy 1953
models of medical practice 64Modiﬁ  ed Card Sorting T est 90
Modiﬁ  ed Six Elements T est 90
Modiﬁ  ed Social Stress Model 505
mogo laya  984
molecular genetics 1598
gene–environment interactions 214–18, 221, 
229, 315, 558–9, 1608, 1725

intermediate phenotypes 221
molindone 1209
Mongolia, attitudes to psychiatric disorder 6
monoamine oxidase-A (MAO-A)
and aggression 889, 1918
and antisocial personality disorder 315, 1918
and conduct disorder 1658
monoamine oxidase inhibitors (MAOIs)
adverse effects 674, 1187–8, 1190, 1191 ,
1192, 1192
in anxiety disorders 1182in attention-deﬁ  cit hyperactivity 
dietary interactions 1187–8, 1192, 1192
drug interactions 1175, 1194–5, 1195
introduction 1185, 1185
irreversible 670, 670, 1187
pharmacodynamics 1173, 1186–7, 

reversible 1187
monoamines
and depression 662
inhibition of reuptake 1172, 1173
and phototherapy 1260
monosomy 228
Montreal Cognitive Assessment 1536
mood
in alcohol withdrawal 439
deﬁ nition 54, 629
delusional 51, 611
depressed 637
immune modulation 209
Mood and Feelings Questionnaire 1675, 1780
Mood Disorder Questionnaire 635mood disorders 54–5
aetiology
genetic 650–8
alcohol-induced 427, 434, 444, 455anticipation in 652
in cancer 1102, 1102 ,1103
childhood and adolescence 1669–80
with intellectual disability 1852neurocognitive factors 1674–5

classiﬁ  cation 104, 105, 631, 638–43 , 665
clinical features 632–7
concept of unipolar and bipolar 
disorders 631
course and prognosis 665–9
deﬁ nitions 637–8
and delusional disorder 614diagnosis 637–45
stability of 665
differential diagnosis 643–4
elderly people 1550–8
epidemiology 645–50
, 650–1
genetics 658
history of 629–31
and life events 269–73, 270,271, 659
maintaining factors 659–63
and memory 59

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022mood disorders ( cont.)
neurobiology 658–65
neuropathology 181–2, 182
and neuroticism 658
organic 1552
632,633
disorder 1032
and physical illness 1128
precipitating factors 659prevalence 285
prevention 1448, 1675–7
with psychotic symptoms 864
rapid cycling 636, 668
risk factors 658–9
and sexuality 825social functioning in 653
and socio-economic status 654
subthreshold 680–92
and temperament 654, 658, 680
thinking in 52
treatment 669–80 , 1252–4
phototherapy 1261
see also speciﬁ  c disorders
mood stabilizers 1198–208
in childhood and adolescence 1798, 1852see also speciﬁ  c drugs
Moodgym 1406
MOPS (Measure of Parenting Style) 286moral development, history-taking 1601
moral judgement 235
‘moral treatment’ 17, 1392

morality, conventional/pre-conventional 1762
morbid risk 215morbidity
continuous measures 283
hidden and conspicuous in primary 
care 1482
and poverty 278
Morel, Bénédict-Auguste 521
Moreno, Jacob 1353morphine 430
metabolism 473, 474
morphometry 195, Plate 9
Morquio syndrome 1843mosaicism in Down syndrome 1839
motility disorder 58, 58
motivated sleep phase syndrome 1700Motivational Assessment Scale 1823
motivational enhancement therapy 451, 794
motivational interviewing
in alcohol use disorders 451
and adolescence 1779
in opioid dependence 477, 477, 479

in rehabilitation 1400in substance use disorders 428motor co-ordination in schizophrenia 529
motor neurone disease 348
with dementia 344, 345, 347, 348
motor skills disorder 1623, 1623 , 1631
motor symptoms and signs, descriptive 
phenomenology 58–9
mourning 724
pathological 296
religious ceremony 1419
movement disorders
in conversion disorder 1016, 
1016 , 1017
differential diagnosis 373
MR (morbid risk) 215
MRC
framework for evaluation of complex 
intervention 1465, 1466
Needs for Care Assessment 73, 1433–4
MRI see structural magnetic resonance imaging
MSE see mental status examination
MSI-II (Multiphasic Sex Inventory II) 1962
MSLT see multiple sleep latency test
mtDNA see DNA, mitochondrial
MTFC (Multidimensional Treatment Foster

MTFC (Multidimensional Treatment Foster 
Care) 1790, 1953
mucopolysaccharidoses
classiﬁ  cation 1843
muddling 53
MUDs (medication use disorders) in elderly 
multiaxial descriptive systems 73, 990, 990
in childhood and adolescence 1592–3
Multidimensional Treatment Foster Care 
1790, 1953
multi-disciplinary practice 68
multi-disciplinary team
agreement on terminology used 64
in Alzheimer’s disease 341
care planning 68–9
in child and adolescent mental health 
services 1812
and clinical assessment 62, 68
community mental health teams 584, 
community old age mental health 
services 1582
key worker/case manager 68–9
leadership 68
membership 68–9

for people with intellectual disability 1888
values in 33–5, 34
values-based practice 34, 35, 36
multi-disciplinary teamwork 68Multiphasic Sex Inventory II 1962
multiple causation 314
multiple chemical sensitivity 997, 1002
multiple family group therapy 1382, 1389
multiple personality disorder 56, 1923multiple regression analysis 217
cognitive impairment in 1074
depression in 1074
emotional lability in 1074euphoria in 1074psychotic symptoms 1074
multiple sleep latency test (MSLT) 930, 939, 945
in childhood and adolescence 1697
multi-sensory therapy 414
multisomatoform disorder 998, 1000
multi-system atrophy 364, 942
multisystemic therapy 1598, 1661–2, 1782Munchausen syndrome see factitious disorder
Munchausen syndrome by proxy 1054, 1697, 

muscarinic agonists in Alzheimer’s 
disease 1241
muscle dysmorphia 1044–5
mushrooms, hallucinogenic 488
music therapy 414, 1352
mutism 54, 58, 
58
selective 1639, 1714
MWT (maintenance of wakefulness test) 939
myalgic encephalomyelitis see chronic fatigue 
syndrome
myelasthenia 1060
myelencephalon 157
myocardial infarction 649, 1081–2
myocardial ischaemia 1081–2
myopathy
in anorexia nervosa 785
myotonic dystrophy 228
myriachit  983
mysophilia 833
mythomania 54
myxoedema and sleep-wake disorders 932
nadolol 1876
Nagel, Thomas 135
nail-biting 918nalmefene 454
naloxone 473, 475, 479, 1232, 1245
in pregnancy 1118
naltrexone

in alcohol use disorders 454, 1542
in opioid use 477, 1245
naratriptan 1171narcissism 57, 296
healthy 311
history of concept 870
malignant 870, 871
types 870
narcissistic loss 1106
narcissistic personality disorder 296, 870–2
aetiology 871
classiﬁ  cation 856, 871, 871
clinical features 871comorbidity 857–71
course and prognosis 872
diagnosis 871
differential diagnosis 871, 876in elderly people 1562
epidemiology 871, 882, 883
historical perspective 870treatment 871–2

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022narcolepsy 940–1 , 1695, 1701
with cataplexy 940–1
in physical illness 941
and schizophrenia 927
without cataplexy 941
Narcotics Anonymous 477, 477, 1279
NARIs (noradrenaline reuptake inhibitors) 
670, 670
narrative gerontology 1514–15
National Adult Reading T est (NART) 264, 389
National Comorbidity Survey 541, 645
National Comorbidity Survey Replication 
1595, 1596
National Conﬁ  dential Inquiry into Suicide 
and Homicide by People with Mental Illness 1937, 1938, 1939
National Drug and Alcohol Treatment 
Utilization Survey 463–4
National Drug Treatment Monitoring 
System 515
National Health Service and Community Care 
Act 1432
National Healthy School Standard 1814
National Institute for Health and Clinical 
Excellence (NICE) 789
clinical practice guidelines 124
National Institute of Neurological and 
Communicative Disorders and Stroke–AD 
and Related Disorders Association 336, 348

National Institutes of Mental Health 23
National Psychiatric Morbidity Survey 645, 647
National Schizophrenia Fellowship 1490–1
National Service Framework for Children, 
Y oung People and Maternity Services 1946
National Survey of Health and 
Development 1911, 1912
National Survey of Sexual Attitudes and 
Lifestyles 821
National Trailblazer network 1487–8National Treatment Agency for Substance 
Misuse 515–16
National Treatment Outcome Research 
Study 1927
NATSAL (National Survey of Sexual Attitudes 
and Lifestyles) 821
nausea in alcohol withdrawal 439
NDATUS (National Drug and Alcohol 
Treatment Utilization Survey) 463–4
nDNA see DNA, nuclear
necrophilia 833
needs 1432–7
for action 1433
assessment 73, 94, 1433–5, 1435 , 1823–4
population-level 1434–5, 1435 , 1459
deﬁ nitions 1432–3

in evaluation of mental health services 1465
of families with a member with intellectual 
disability 1885–6
hierarchy of 1432
for improved health 1432
needs-led care planning 1432
patient and staff perceptions 1433
relationship between individual and 
population 1435
for services 1433
Needs for Care Assessment 73
nefazodone
dosage 1196pharmacodynamics 1187 , 1188
negation 294
negative automatic thoughts 761, 1165, 1286, 
1287–9, 1287 , 1291–2, 1304–5, 1306, 1306 ,
1307, 1308–10, 1309
negative emotionality
negative images 1288
negativism 58negativistic personality disorder see passive–
aggressive personality disorder
negligence 1901–2
clinical 1902
difference between acts and omissions 1905

liability of mentally ill people 1903–4
liability to mentally ill people who self-
harm 1905
liability of providers of mental health 
services 1904–5
liability for psychiatric injury 1902–3
liability to third parties for acts by mentally 
ill people 1901–5
NEO Personality Inventory-Revised (NEO 
PI-R) 81, 81, 654, 847–58, 858, 887, 1164
neo-behaviourism 134–5
neocortex 202
in absence epilepsy 204
connection 149, Plate 1
development 158–9, 159
in epilepsy 203and memory 253
and priming 254
structure 147, 148, Plate 1
neologisms 54
neonates
abilities 238
cocaine withdrawal syndrome 1118
death of 1119
narcotics withdrawal syndrome 1118
neonaticide 1118–19, 1125
nerve gas 1241
nerve growth factor 160, 966
nesting behaviour 1117
neural crest 156neural groove 156

neural plasticity 251
neural plate 156
neural tube 156, 157neurasthenia 993, 994, 1003, 1035, 1059–64
aetiology 1062–3
classiﬁ  cation 1062
comorbidity 1063concept of 1059–60
course and prognosis 1063
and culture 1060–1current usage 1062
deﬁ nition 1060
as diagnostic entity 1059–60
differential diagnosis 1062
epidemiology 1062, 1062
and stigma 1040
treatment 1063
neuregulin 1 (NRG1) gene 179, 230, 555, 565
neuroanatomy 144–56
neurobehavioural teratology 1614neuroblasts 157
neurocirculatory asthenia 751neurodevelopment 156–60
brainstem histogenesis 158–9
cerebellum histogenesis 158
cerebral cortex histogenesis 158–9, 159
CNS organogenesis 156–7, 157
environmental risks 1724
genetic factors 159hemispheric shape and formation of 
gyri 159, 159

spinal cord histogenesis 157–8
neurodevelopmental disorders 1613
alcohol-related 1615, 1841
genetics 159
neuroectoderm 156
neuroendocrine ‘window’ strategy 161
neuroendocrinology 
160–7 , 205, 781, 889
neuroﬁ  brillary tangles in Alzheimer’s 
disease 337–8, 339
neuroﬁ  bromatosis type 1
behavioural and psychiatric aspects 
1075, 1844
genetics 1843, 1866
physical characteristics 1843–4
neuroﬁ  bromatosis type 2, psychiatric 
aspects 1075
neurokinins 171
neuroleptic malignant syndrome 1223, 1531
and malignant catatonia 529
neuroleptics see antipsychotics
neuroligins 227neurological disorders 1071–6
neuromodulators 168

neuronal ceroid lipofuscinoses 1865, 1866
hippocampal 202–3, 202
realistic computer simulations 203
neuronal speciﬁ  c enolase 353
neurones
death from traumatic brain injury 387
development 157
endocrine functions 160–7
neocortical 148, 148
in schizophrenia 178, 180
NeuroPage 423
neuropathology 177–85
alcohol use disorders 182–3, 183
Alzheimer’s disease 337–9
corticobasal degeneration 345
delirium 330–1, 330
frontotemporal dementia 344–5
head injury 387–8, 387
mood disorders 181–2, 182
Pick’s disease 344
progressive supranuclear palsy 345
schizophrenia and psychoses 178–81, 178,
179,180,181
neuropeptides 168, 170–1, 171, 206
neuropores 156

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022neuropsychiatry
developmental 1612–22
history of 20
neuropsychological assessment 262–7
in Alzheimer’s disease 265–6
in attention deﬁ  cit hyperactivity disorder 266
in childhood and adolescence 1590–1, 1605
domains 263–6
functions 263head injury 389in HIV-associated dementia 384–5in mild cognitive impairment 1536
in obsessive–compulsive disorder 266
principles 263
in transient global amnesia 403
neuroses
historical background 20–1
neurosurgery for mental disorder (NMD) 769, 
1266–9
adverse effects 1268–9
deﬁ nition 1266
ethical considerations 1267–8
historical overview 1266–7
inclusion and exclusion criteria 1268
indications 1267mechanism of action 1268
outcomes 1268
procedures 1267, 1269 ,1270
stereotactic procedures 1267
neurosyphilis 537, 1093neurotic (stress-related) disorder, elderly 
people 1558–61

course and prognosis 1560diagnosis and differential diagnosis 1558–9
neuroticism 81, 81, 850, 886
and body dysmorphic disorder 1046and high health service use 1137
and mood disorders 658
and serotonergic system 887–8
and subthreshold mood disorders 680subtypes 632
neurotransmitter receptors 172
drug actions at 1171
agonist 1171
antagonist 1171–2partial agonist 1172
ionotropic 1171
metabotropic 1171
neurotransmitters 168–77
chemokines and cytokines as 171
co-localization with neuropeptides 171
deﬁ nition 168
and drug pharmacodynamics 1173
hippocampus 202as hormones 161
neuropeptides 170–1, 171
and phototherapy 1260primary 429

principles of transmission 168, 169
retrograde messengers 171–2
role in neurodevelopment 159secondary 429
small molecule 168
in substance use disorders 429, 429, 435–6
transporters 168–70, 170
plasma membrane 169–70, 170
vesicular 170, 170
see also speciﬁ  c substances
neurotrophic factors 159, 160,168, 171, 1186
see also speciﬁ  c factors
neurotrophin receptors 158
neurovascular coupling 197
neutralizing activities in obsessive-compulsive 
disorder 1783
New Zealand, Mental Health Foundation 1491
Newcastle Thousand-Family Study 1910
Newton, Isaac 133
NGF (nerve growth factor) 160, 966
NGOs (non-governmental organizations) 1491
Nicaragua, attitudes to psychiatric disorder 6
NICE see National Institute for Health and 
Clinical Excellence
nicotine replacement therapy 512

nicotine use see smoking
nidotherapy 896–7, 904–5
nifedipine 1201
night-eating syndrome 931, 947–8
night-time fears 1698–9
nightmares 1108, 1702
in post-traumatic stress disorder 701
nihilistic delusions 56
nimodipine 1198, 1201, 1203
adverse effects 1200 , 1204–5
drug interactions 1206
in HIV-associated dementia 385indications and contraindications 1205
pharmacokinetics 1201
withdrawal 1207
NINCDS–ADRDA 336, 348
Nisonger Child Behaviour Rating form 1850
nitrazepam 1172 , 1179
nitric oxide, as retrograde messenger 172
nitroglycerin in HIV-associated dementia 385nitrous oxide 503
NMD see neurosurgery for mental disorder
NMDA receptors 172, 173, 231, 1171
action of lithium at 1201

in alcohol withdrawal 443antibodies against 1086
and depression 1186
and long-term plasticity 251
and long-term potentiation 251
NMR (nuclear magnetic resonance) 191–2
NNT (number needed to treat) 127, 128, 128
NO as retrograde messenger 172
‘no-suicide’ contracts 1707
nocebo effects 1141nociception 473
nocturnal enuresis 1702
nocturnal penile tumescence 825, 930
nominal scales 85–6
non-compliance see treatment, non-compliancenon-experimental descriptive studies 1468–9
non-governmental organizations 1491
nootropic agents 1240noradrenaline reuptake inhibitors 670, 670
noradrenergic storm 473, 476
noradrenergic system and noradrenaline 
receptors 173, 482, 1171, 1172
and depression in childhood and 
adolescence 1675
noradrenaline transporters 169, 170

in post-traumatic stress disorder 706and sexual function 826
and substance use disorders 429and suicide 965
nordiazepam 1178
norepinephrine see noradrenergic system and 
noradrenaline receptors
Northﬁ
 eld Hospital 1353
nortriptyline 670
dosage 1195, 1196
Notch protein 339
notochord 156
novelty-seeking 80, 80, 316, 316, 654, 849, 
886–7
NRT (nicotine replacement therapy) 512NSE (neuronal speciﬁ  c enolase) 353
NT-3 160
NTA (National Treatment Agency for Substance 
Misuse) 515–16
nuclear magnetic resonance 191–2nucleosomes 223, 225
nucleus accumbens 154
in substance use disorders 430
nucleus basalis of Meynert, in Alzheimer’s 
disease 1240

number needed to treat 127, 128, 128
Nuremberg Statement 30
oats 1248
obesity
psychiatric disorders associated 1084
and schizophrenia 546
object relations 295, 306–12 , 313, 1337
Balint’s work 308–9
Bion’s work 307–8
Bowlby’s work 309–10
and character 316
conﬂ  ictual model 308
and countertransference 298–9
deﬁ cit model 308
development from drive theory 306
Fairbairn’s work 308
internalization 301–2
Klein’s work 306–7, 308
overview and critique of psychoanalytic 
theories 301–3
and personality development 316
and psychoanalytic treatment 297
and transference 298–9
unconscious internal 297, 314

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022Winnicott’s work 309
object representation 298, 302–3
Objective Opiate Withdrawal Scale 478, 478
observed score ( x) 85
obsessions 52, 53, 1680
as conditioned stimuli 768
in obsessive–compulsive disorder 765–6and querulous behaviour 1979
obsessive–compulsive disorder (OCD) 765–73
aetiology 767–8, 1683–5
and anorexia nervosa 783assessment 1783and body dysmorphic disorder 1044, 1045
in cancer 1101
childhood and adolescence 1613, 1680–93
clinical features 1680–1comorbidity 1681–2
with intellectual disability 1852prevention 1690
refractory 1688
classiﬁ  cation 856, 1682
clinical features 765–6, 1680–1cognitive content 1287
comorbidity 765, 1681–2
course and prognosis 766–7, 1685
diagnosis 765–6, 1682–3

differential diagnosis 766, 863, 875–6, 1004, 
1023–4, 1639, 1682–3
elderly people 1558
epidemiology 765, 1683
genetics 768, 1684
neuropsychological assessment 266and offending 1923
puerperal 1121–2and schizophrenia 766
stalking as 1972
and tic disorders 765, 1073, 1681treatment
in childhood and adolescence 1685–90, 
1686 ,1687 , 1783–4
cognitive-behaviour therapy 770, 1686–7, 
deep brain stimulation 769, 1270
long-term 769
neurosurgery 769, 1267, 1268
pharmacotherapy 768–70, 1193, 1686 ,
1687–8, 1687
psychological therapies 770, 1783–4
transcranial magnetic stimulation 1265
obsessive–compulsive personality disorder 
765, 874–6
aetiology 874
classiﬁ  cation 874, 874
clinical features 875

765, 874–6
course and prognosis 875defence mechanisms 317
differential diagnosis 875–6in elderly people 1562, 1562
treatment 876
obstetric complications
and schizophrenia 548, 555–6
obstetric liaison services 1118, 1124obstructive sleep apnoea (OSA) 928, 1083
early-onset 1695, 1700
in elderly people 1572
hypersomnia in 939–40
occipital lobe 146, 147
occupation, and risk of suicide 976occupational therapy 1034, 1351–2, 1400–1
OCD see obsessive–compulsive disorder
OCEAN 850
odds ratios 126, 127, 128, 141, 282
oedema, famine 785
Oedipus complex 307
negative 294
positive 294–5
and the superego 296
Oenothera biennis oil 1249, 1250
oesophageal dysmotility 1083
oestrogens 816, 826
therapy

therapy
in gender identity disorder 843sex offenders 1963–4
off time 1515
offenders
amnesia for crimes 405, 1927
art therapy 1415assessment 2011–12, 2018
depression 1923
group therapy 1365
mental health services for
development 1934–5forensic 1459, 2013, 2015–21
need for psychiatric assessment and 
treatment 1918
outcome assessment 2020
sexual see sex offenders
therapeutic communities 1396
treatment 2012–13, 2018–20, 2019
versatility 1909
see also  prisoners
offending
acquisitive 1927
in adolescence see juvenile delinquency
amnesia for 405, 1927
and autism 1921
and child abuse and neglect 1910and child-rearing practices 1910
and cognitive disorder 1928–32
and community inﬂ  uences 1913–14

concentration in families 1659, 1911–12
2011, 2012
and delusional disorder 1920and dementia 1920–1
epidemiology 1908–9
and epilepsy 1079–80, 1920, 1929–31and gender 1909genetic factors 1918
and head injury 1920
and hyperactivity and impulsivity 1909impact of criminal victimization 1984–90
and impulse control disorders 1924
and intelligence 1909–10
and marital conﬂ  ict 1911
measurement 1908–9and mental disorder 1917–26 , 2009–10
and mood disorders 1923
neurobiological determinants of 1917–18
and neurotic disorders 1923
and opioid use 474, 480and peer inﬂ  uences 1912–13
and personality disorder 865, 866, 1921–3
protective factors 1909
psychosocial causes 1908–16
risk factors 1909
family 1910–12

individual 1909–10social 1912–14
and schizophrenia 1918–20
and school inﬂ  uences 1913
self-reported 1908
and situational inﬂ  uences 1914
and socio-economic status 1912
and substance use disorders 1926–8
and violence 1918, 2010–11
Ohtahara syndrome 1862olanzapine 1209, 1209
administration 1214 , 1217–18
adverse effects 1212 , 1224
in bipolar disorder 672
in childhood and adolescence 1677, 1797
in delirium 331in dementia 415
pharmacodynamics 1210, 1211 , 1213
pharmacokinetics 1221
old age/older people see elderly people
olfactory pathways to the cerebral cortex 
147, 152
olfactory reference syndrome 618
olfactory tubercle 154omega-3 fatty acids 1248, 1250 , 1676
omnipotence 298
omnipotent control 298

147, 152
on time 1515
One Day Fluctuation Assessment Scale 363oneiroid state 60, 392, 603, 605
onychophagia 918
onychotillomania 618, 918
‘open-loop’ tasks 254
openness 850opiate neurotransmitter pathway, in substance 
use disorders 429
opioid antagonists see naloxone; naltrexone
opioid receptors 173, 473, 1171
opioid substitution/maintenance 
treatment 475, 476, 479, 1243–4
opioids 473–82
as anxiolytics 1178
complications of use 474–5, 475
deﬁ nition 473

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022opioids ( cont.)
dependence 473, 474
outcome 481
psychiatric comorbidity 475, 492–3
relapse prevention 477
treatment 475, 476–8, 479, 1242–7
effects 474
neurobiology 473
and offending 474, 480
1117–18, 1615–16, 1754
routes of use and risk associated 430, 473
tolerance 473, 474
assessment of 478
use by elderly people 1543
withdrawal 473, 474
opioids, endogenous 170, 171, 429
opium 473
opportunity costs in service planning 1459oppositional deﬁ  ant disorder
comorbidity 1682
diagnosis 1656
with intellectual disability 1851treatment 1781–2
optic nerve development 157

optical distortions 49
optimism
and health 1136and immune function 207
OQ-45 1165
oral contraceptives, drug interactions 1174
oral phase of development 294, 295
orbitofrontal cortex 146, 1919ordinal scales 86, 95
orexin (hypocretin) 930, 941
orgasm 812
female 818–19
problems 823
male 817
delayed/absent 828
ORLAAM® 1243–4
OSA see obstructive sleep apnoea
osteoporosis in anorexia nervosa 785
Othello-type syndrome 1967
out-of-body experiences 1012outcome measures 73
in evaluation of mental health services 
1464–5, 1464
psychometric properties 1465
outpatient care in community mental health 
services 1454
ovaries, in anorexia nervosa 784, 787
overactivity in attention-deﬁ  cit hyperactivity 
overdetermination 314oversedation 1178, 1180overstimulation and hallucinations 50
overvalued ideas 52, 57, 611, 803
oxazepam

oxazepam
oxcarbazepine 1198, 1237
adverse effects 1204
dosage and administration 1233
oxiracetam 1240
oxytocin 815, 888
P-glycoprotein 1170, 1249–50, 1250
p11 175p73 protein 158
P300 event-related brain potential 435
Paced Auditory Serial Addition T est 87–8, 88
paediatric autoimmune neuropsychiatric 
disorder associated with streptococcal 
infection 1073, 1685
paedophilia 832, 833,836, 1960–1, 1962
pain
acute 1029, 1033
affective dimension 1033
assessment 1032–3assessment instruments 1032–3
behaviours 1032, 1033
beliefs 1032, 1033
in childhood and adolescence 1744–5chronic 1029, 1030, 1033
neuropathic 1265

clinics/treatment centres 1034deﬁ nition 1029
and delusions 1030
in dementia 418
and depression 1029, 1030
during sexual arousal 822following an accident 1107, 1110
history 1032
low threshold 1096in mood-/anxiety-related disorders 1030
non-operant 1033
non-organic 1784
operant 1033
in organic disorders 1030postoperative management 1099
and post-traumatic stress disorder 
1030–1
and the psychiatrist 1029
psychogenic 57
as a psychopathological entity 57
and psychoses 1030
psychosocial contributions to 
development 1033
sensory dimension 1033
and somatization 1030, 1031–2and somatoform disorders 1031–2
and substance use disorders 427
syndromes of uncertain origin 1030
topographical distribution 1033
treatment and management 1033–4
pain disorder see persistent somatoform pain 
disorder

disorder
paired matching 1468PAL (CANTAB Paired Associate Learning test) 
264, 266
palaeocortex 158
palilalia 346, 1681
palimpsest 59
paliperidone 1209, 1209
administration 1214 , 1220
adverse effects 1225
palliative care in dementia 418
palm sign 487
palmar erythema in alcohol use disorders 446
Panax ginseng
pancreas, effects of alcohol use disorders 446
PANDAS 1073, 1685
panic attack/panic disorder 750–64
aetiology 753–5
with agoraphobia 740–1, 750–64
and alcohol use disorders 455, 752
biological models 754–5
prevalence 1666
classiﬁ  cation 751
clinical features 750–1
cognitive content 1286

comorbidity 752, 761
and COPD 1082
course and prognosis 755
and depression 752
diagnosis 752–3
differential diagnosis 752, 753, 1004, 1023, 
1078, 1864
epidemiology 753
following an accident 1106
genetics 753–4
hallucinogen-induced 488
in HIV/AIDS 1091and hypochondriasis 997
limited symptom attacks 751
nocturnal attacks 751
in physical illness 1131and pregnancy 761–2
prevention 762
prevention of recurrence 759
in primary care setting 753
puerperal 1121risk factors 753
and separation anxiety disorder 1665
situational attacks 750
situationally predisposed 750
and sleep disorders 1697with social phobia 750
treatment and management 755–62, 1180
cognitive-behaviour therapy 758, 761
continuation/maintenance 758discontinuation 760
ethical issues 762

exposure treatments 758, 760–1
hyperstimulation reaction 756, 759–60
pharmacotherapy 755–7, 756
psychodynamic psychotherapy 758

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022resistance to 761
Panic Disorder Severity Sale 760
Papaver somniferum  473
papaverine 1240
Papez circuit 733
para-aminosalicylate 1091
paracetamol poisoning 973
paradoxical intention in insomnia 937
paradoxical interventions 1377
paragrammatism 54
parahippocampal gyrus 146, 153
paraldehyde 1178, 1867
paralysis 57
in conversion disorder 1016
paramnesia 59
paraneoplastic syndromes 1101paranoia
deﬁ nition 861
elderly people 1546–50 , 1559
querulous see delusional disorder, litigious
see also  delusional disorder
paranoia acuta 603, 605
paranoid personality disorder 861–2
aetiology 861
classiﬁ  cation 856, 861, 861
clinical features 861–2
course 862
defence mechanisms 317
differential diagnosis 862, 863, 865
epidemiology 861, 882, 882
nomenclature 610
treatment 862, 898
paranoid psychoses following head injury 
392–3
paranoid–schizoid position 307
‘paranoid spectrum’ 609, 610–11
paraphasia 54

392–3
paraphilias 832–42 , 1961
aetiology 836–7assessment 1962
classiﬁ  cation 833–4, 833
clinical features 832–3
co-occurrence 1962
comorbidity 834–5course and prognosis 837–8
diagnosis 834–5
differential diagnosis 834–5
epidemiology 835, 836
false confessions 834
and intellectual disability 834
legal issues 834
overlap with sexual offences 1960
treatment and management 838–41, 839,
1963–4
paraphrenia 609, 610, 623
late 1547
paraplegia, in conversion disorder 1016
parapraxes 313
paraschemazia 57
parasitosis, delusion of 50, 51, 618parasomnia pseudo-suicide 948
parasomnias 927, 928,943–50 , 1695
in childhood and adolescence 1701–2
classiﬁ  cation 944, 944
clinical evaluation 943, 944–5, 945
deﬁ nition 943differential diagnosis 948

overlap disorder 947
relevance to psychiatrists 943–4
parasuicide 916–17, 957, 1703parasympathetic nervous system 156parasyntax 54parathyroid adenoma 1101
Parent–Child Interaction Training 1788–9
Parental Bonding Instrument 286, 648
parenting
and attachment 309
and conduct disorder 1659–60, 1661, 1662
and gender identity disorder in childhood 
and adolescence 1719–20
and mood disorders 653
negative 1788, 1789
positive 1788, 1789
style 286
parents
abusive 1734
and assessment in childhood and 
adolescence 1600, 1602, 1603 , 1605
in child and adolescent psychiatric 
emergencies 1808, 1809
child’s reaction to death of 1758–60
conﬂ  ict between

and depression 1753effects on child mental health 1726
interpersonal psychotherapy 
(IPT-CM) 1322
and offending 1911
disability 1884, 1885
factors affecting child mental health 1726–7
good-enough mother 309
inﬂ uence on childhood and adolescent sleep 
disorders 1694
interviewing 1601, 1603
involvement in cognitive-behaviour 
therapy 1778–9, 1780
involvement in pharmacotherapy 1794
involvement in psychotherapy 1768, 1771
late-life 1514
alcohol use disorders 1754
anxiety disorders 1754depression 1752–3
eating disorders 1753–4
effects on child development 1752–4, 
1755–6
schizophrenia 1753

1755–6
substance use disorders 1754
neglectful 1736
people with intellectual disability as 1885
cancer 1754–5
effects on child development 1754–6
HIV/AIDS 1755
single 1369–70, 1601, 1726–7, 1910, 1911training programmes 1661, 1787–93in attention-deﬁ  cit hyperactivity 
in conduct disorder 1782
young 1910
parietal lobe 146, 146
parieto-occipital sulcus 145
parkinsonism
in dementia with Lewy bodies 361drug-related 580, 1222–3with frontotemporal dementia 344–5, 
346, 348
treatment 1255
Parkinson’s disease 1072–3
cognitive assessment 92dementia in 92, 362–3, 368–71 ,370
depression in 648–9, 1072
diagnosis 369
differential diagnosis 373dopamine dysregulation syndrome 1073
hypersomnia in 942
Lewy bodies in 361, 369
mortality in 370

psychotic symptoms in 1072
sleep-wake disorders 
932, 1072
paroxetine 670
in attempted suicide 970–1
partial arousal disorder 1702
partnerships 40
parturition see childbirth
PAS (Personality Assessment Schedule) 
858, 859
PASAT (Paced Auditory Serial Addition 
T est) 87–8, 88
Passiﬂ  ora incarnata  (passion ﬂ  ower) 1248, 
1249, 1250
passive–aggressive personality disorder 876,
876–7 ,1562
epidemiology 882, 883
passivity experience 56

1249, 1250
passivity of thought 53
path analysis 217, 217
pathological jealousy 51, 620–1, 862, 1998
pathological lying 54, 871, 1049, 
1051, 1941
pathways to care 281, 281
and culture 1438–45
ﬁ lters on 1440–2, 1441
international comparisons 1438–9, 1439
pathways out of care 1443
patient delay 1137
patient expected event rate 128
Patient Health Questionnaire 1145
Patient Health Questionnaire-9 
1484, 1486
patient-intervention studies 1139

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022patients
education 4, 1198
expectations, and the placebo response 1142
information for 1140
perceptions of need 1433
perspective on services 3–4
protection, and psychiatric reports 75
satisfaction 1138–9, 1465
Pavlovian theory 1061
PBI (Parental Bonding Instrument) 286, 648
PCIT (Parent–Child Interaction 
Training) 1788–9
PCL-R (Psychopathy Check List-Revised) 
1921, 2011
PCMHWs (primary care mental health 
workers) 1485
PCP see phencyclidine
PCR (polymerase chain reaction) 223, 226
PDsee personality disorders
PDA (panic disorder with agoraphobia) 740–1, 
750–64
PDDs see pervasive developmental disorders
PDEs (phosphodiesterases) 176
PDQ-4 (Personality Diagnostic Questionnaire-
Revised) 858
PDS (Post-traumatic Stress Diagnostic 
scale) 703
PDSS (Panic Disorder Severity Sale) 760PEA (prenatal exposure to alcohol) 1841
PEER (patient expected event rate) 128
peer pressure, and substance use disorders 427

scale) 703
peer relationships, and conduct disorder 1659
pellagra 1447pemoline 1648, 1652
penetrance 213
penicillin
in syphilis 1094
penile plethysmography 840, 1962, 1964
penis
erection 816–17
Penn State Worry Questionnaire 1163pentagastrin in panic disorder 754
pentosan polyphosphate 359
pentoxifylline in HIV-associated 
dementia 385–6
peptic ulcer disease 932, 1084
peptide T in HIV-associated dementia 385
percentile 86, 86
perception
and consciousness 59
delusional 51, 527–8disorders of 48–50
disturbance in schizotypal personality 
disorder 864
and emotion 259–60
perceptual priming 696
perfectionism
in bulimia nervosa 804, 806and chronic fatigue syndrome 1036
and psychoanalysis 1341
and somatization disorder 1002
periodic limb movements in sleep 948, 1572,

periodic limb movements in sleep 948, 1572, 
1695, 1700
peripheral nervous system, in mood 
disorders 182
peripheral neuropathy
in alcohol use disorders 446disulﬁ  ram-induced 453
peripheral oedema in anorexia nervosa 784
perirhinal cortex 146, 152–3, 153, 252, 406
periurethral glans 818
perphenazine 1209
persecution, delusion of 51
perseveration 53
persistence 80, 80
, 316, 316, 849
persistent genital arousal disorder 822
persistent somatoform pain disorder 57, 993,
1003, 1029–35
assessment 1032–3
assessment instruments 1032–3
classiﬁ  cation 997, 1029–30
comorbidity 1031 , 1032
correlates 997
diagnostic and clinical features 1029–30
differential diagnosis 1003, 1029, 
1030–2, 1031

epidemiology 997, 998, 1032
phenomenology 997
prevalence 997, 998
prognosis 1034
and psychosocial contributions to 
development of pain 1033
persistent vegetative state in Huntington’s 
disease 373
Personal, Health and Social Education 1814
personality
abnormality 60accentuated type 73
and addiction 428–9
and alcohol use disorders 434
in Alzheimer’s disease 335–6
assessment 72–3, 78–85 , 286, 1164–5
change
due to a general medical condition 
879, 1929
following traumatic experiences 879, 
1110–11
and character 316–17
deﬁ nition 60, 79, 855
and depression 648
development 316
psychodynamic approaches 316–17
domestic violence perpetrators 1982
effects of neurosurgery for mental 

histrionic 868, 869
hysterical 868, 869
models 848–50
categorical 849
correlational 849
dimensional 849–50
experimental 849
Five-Factor 238, 850, 857–8, 1164and personality disorders 850–1
psychoanalytical 849psychobiological 316neuropsychology 886–92
premorbid 1526
quantitative description of 79–81, 80
studies 848
and subthreshold mood disorders 680
and temperament 316, 316
traits 79–81, 80, 286, 849–50, 855, 857, 886
biological factors 886–92
and genetics 886–8, 888–9, 890
and head injury 390
normal/abnormal 857
psychometric testing 81–2, 81
type A 1082, 1136
type B 1136
type D 1082, 1136
typology 60
variants 852–3, 852
Personality Assessment Inventory 1962
Personality Assessment Schedule 
858, 859
Personality Diagnostic Questionnaire 1562

type B 1136
858, 859
Personality Diagnostic Questionnaire-
Revised 858
Personality Disorder Questionnaire 1164
personality disorders (PD) 847–55
assessment 858–9, 858
changes in conceptualization 857
and character dimensions 316
classiﬁ  cation 106, 850–1, 851, 852, 852,853,
855–8, 856
cluster A 856, 861–5
drug treatment 906and reward-dependence 316
cluster B 856, 865–72
and attempted suicide 1704
drug treatment 906
and novelty-seeking 316
cluster C 856, 872–6
and harm-avoidance 316
long-term psychodynamic 
psychotherapy 318
comorbidity 780–1, 803, 884, 893, 902, 907
course 892–3
dangerous and severe 848, 2015, 2018
deﬁ nitions 60, 855, 893
and depression 649diagnosis 855–60 , 890–1
distinction from personality variants 
852–3, 852
elderly people 1561–4

852–3, 852
diagnosis 1562
epidemiology 1518, 1562–3, 1562
epidemiology 881–6
community studies 882–3, 882
studies in a psychiatric setting 883–4
and epilepsy 1079
features 82
history of concept 847–8and homicide 1921
and models of personality 850–1
and offending 865, 866, 1921–3and persistent somatoform pain 

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022and physical illness 1132
prisoners 1921, 1933, 1933
psychoanalytic approach 294, 296
qualitative clusters and subtypes 83
and stigma 848
stress–diathesis model 851–2
and suicide 955, 956, 969
and temperament dimensions 316in T ourette syndrome 1073
treatment 901–10
adherence to 902
cognitive 895, 903–4
drug treatment 600, 905–6, 905
duration 901–2
evaluation of efﬁ  cacy 901–3
outcome measures 902
psychotherapy 892–901 , 1395–6
service organization 907
therapeutic communities 892, 896, 905, 
1395–6
type R (treatment resisting) 902
type S (treatment seeking) 902
see also speciﬁ  c personality disorders
Personality Disorders Interview-IV 858
PERT (post ejaculation refractory time) 
817, 822
pervasive developmental disorders 
(PDDs) 1613, 1633–42
differential diagnosis 1639
prevention 1640and social phobia 1665

treatment and management 1639–40
pervasive refusal syndrome 787
PET see positron emission tomography
pet therapy in dementia 414
peyote 489
PFAE (possible foetal alcohol effects) 1841
PGAD (persistent genital arousal disorder) 822
phaeochromocytoma 1101phallometry 840, 1962, 1964
phantasy, unconscious 307
phantom bite syndrome 619
pharmacodynamics 1168, 1171–3
in childhood and adolescence 1794
pharmacogenetics 221
mood disorders 653
pharmacokinetics 1168, 1170–1 ,1172
bioavailability 1170
in childhood and adolescence 1794clearance 1170–1
half-life 1170–1
protein binding 1170
pharmacotherapy 1168–77
adjustment disorders 721, 1068
adverse effects 427,1173–5
collateral 1173dose-related 1173
DoTS classiﬁ  cation 1173, 1174

hypersusceptibility 1173
risk factors 1174–5
sexual dysfunction 826–7susceptibility factors 1174–5, 1175time-related 1173–4, 1174
toxic 1173
withdrawal syndromes 1175
alcohol use disorders 1246
Alzheimer’s disease 1240–1attempted suicide 970–1
disorder 1174–2, 1648, 1650, 1876
beliefs about 1141
body dysmorphic disorder 1046–7, 1047–8
in breastfeeding 1121, 1123, 1169–70, 1180
with brief psychodynamic 
psychotherapy 1329
bulimia nervosa 807–8
childhood and adolescence 1793–9
atomoxetine 1795–6
developmental issues 1794
mood stabilizers 1798, 1852
as part of multimodal treatment 1793–4
with psychiatric/behaviour disorder and/or 

chronic fatigue syndrome 1040, 1042in combination with electroconvulsive 
therapy 1257
comparisons with psychotherapy 1162
conversion disorder 1019–20
cosmetic/palliative 853delirium 331–2
in cancer patients 1104
dementia with Lewy bodies 365–7
dosage regimens 1168–70
in childhood and adolescence 1169
elderly people 1169
maintenance dose 1171, 1171
modiﬁ  ed-release (depot) 1169, 1169 ,
1171, 1486
parenteral 1169
in pregnancy and breast feeding 1169–70
drug interactions 1175–6
dynamic 317dysthymia/dysthymic disorder 684–5
elderly people 1573
epilepsy 1231–40
erectile dysfunction 821, 828

following head injury 396–7, 396
generalized anxiety disorder 735, 736, 737
history of 25
hypochondriasis 1027in infectious disease 1091, 1091
mild cognitive impairment 1538
minimum effective dose (MED) 1794
monitoring 1176obsessive–compulsive disorder 768–70, 1686 ,
panic disorder 755–7, 756
personality disorders 600, 905–6, 905
pharmacodynamics see pharmacodynamics
pharmacokinetics see pharmacokineticsin physical illness with psychiatric 
disorder 1130–1
post-traumatic stress disorder 709–10prescribing and management by psychiatric 
nurses 1405–6
in rehabilitation 1400
schizophrenia 579–82, 579, 585, 586–8, 586
social anxiety disorder 742–4
somatization disorder 1009
speciﬁ  c phobia 746
substance use disorders 1242–7

tic disorders 1687–8
vascular dementia 381
phasic alertness 247
phencyclidine (PCP) 486–7
acute physiological effects 486
adverse effects 486
delirium due to 486–7
dependence 487
epidemiology of abuse 486psychosis due to 487, 538
use in pregnancy 1117
phenelzine 670, 670
phenobarbitone 1178
adverse effects 1673
choice of 1866–7drug interactions 1866
phenomenology
descriptive 47–61
phenothiazines in pregnancy 1117, 1118
phenotype 212
components of variation 214

intermediate 221
phentolamine 828
phenylketonuria
1844, 1852
genetics 212, 214, 1844infantile spasms in 1863
physical characteristics 1844
prevalence 1825–6, 1844
phenytoin 1231
adverse effects 1868
drug interactions 1175, 1232, 1866
in epilepsy 1080pharmacokinetics 1170, 1170 ,1867
phobias see speciﬁ  c phobia and other phobias
phobic–anankastic syndromes 52
phonological speech disorder 1624–5, 
1711, 1712
phosphodiesterases 176

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022phototherapy 670, 927, 1260–2
administration 1262
adverse effects 1261–2
drug interactions 1262
forms 1261
indications and contraindications 1261
in insomnia 935mechanism of action 1260
withdrawal 1262
PHQ (Patient Health Questionnaire) 1145
PHQ-9 (Patient Health Questionnaire-9) 
1484, 1486
PHSE (Personal, Health and Social 
Education) 1814
adjustment to 1065–71 , 1741, 1742
antidepressant therapy in 674, 1132art therapy 1415
differentiation from mental disorder 989
differentiation from panic disorder 752, 753
effects on family 1742
group therapy 1364
immune system involvement 209, 210
and intellectual disability 1828, 1850
1754–6
personality change due to 879
with psychiatric disorder 546, 1081–90
in childhood and adolescence 1739–47
course and prognosis 1129–30
depression 335, 371, 648–9, 1072, 1074, 
1080, 1082, 1085, 1086, 1091, 1092, 
1102, 1132

1102, 1132
1129, 1129
epidemiology 1128, 1128
management 1128–34
of refugees 1495
sexual dysfunction in 826
with sleep-wake disorders 931, 932, 933, 
941, 942
see also  illness and speciﬁ  c illnesses
physicalism, a priori  134
physiognomy 1420
physiological deconditioning 1036
physiotherapy in persistent somatoform pain 
physostigmine 331–2, 1241
phytoestrogens 1249
Piaget, Jean 235, 239–40, 239, 1777
pibloktoq  983
pica 1116
Pick bodies 344Pick cells 344
Pick’s disease 228, 344
age at onset 345clinical features 345–6, 346
investigations 347
neuropathology 344
Picture Vocabulary T est 239‘pill bottle’ sign 618
pimozide 1209
pindolol 1172

Pinel, Philippe 17–18Piper methysticum  (kava) 1248, 1250piracetam 1240
Pittsburgh Y outh Study 1908, 1910, 1912, 1913
pituitary
see also speciﬁ  c axes
Place, U.T. 134
placebo response 1141–2, 1794
plaques
plate 12
play
development of 1766
enhancement of capacity for 1772
play therapy 306–7, 1765, 1766, 1770
pleasure principle 294, 295
pleasure-seeking behaviour and 
substance use 426
pleiotropy 224
PLMS (periodic limb movements in sleep) 948, 
1572, 1695, 1700
PMR (progressive muscle relaxation), in 
generalized anxiety disorder 736
pneumonia and delirium 1091Point of Service 45
polar hysteria 983
polyclinics 1454

polycystic ovarian disease and gender identity 
polyembolokoilamania 833
polygraphy, use with sex offenders 1962, 1964
polymerase chain reaction 223, 226
polysomnography 930
1695, 1696, 1699
in hypersomnia 939
in parasomnias 943–4, 943,944
REM sleep behaviour disorder 946–7sleepwalking/sleep terrors 945
POMC (proopiomelanocortin) 170
pooled odds ratio 126
population stratiﬁ  cation 651
poriomania 1930
pornography 1961
porphyria, acute intermittent 212
Portland Digit Recognition T est 1057
POS (Point of Service) 45
positron emission tomography (PET) 185–91 ,
Plates 3–6
alcohol-related dementia 401comparison with functional magnetic 
resonance imaging 186–7, 196–7
comparison with SPET 185
data collection and analysis 186

Plates 3–6
depression 189, 660during antipsychotic use 189–90
during heroin use 428, Plate 13
and emotions 257–8
epilepsy 1619, 1862
frontotemporal dementias 347head injury 389
imaging strategies 187, 187
isotopes 186
production 185
limitations 186–7
methodology 185
mild cognitive impairment 1538obsessive–compulsive disorder 768
schizophrenia 188–9, 562–3
of transcranial magnetic stimulation 1263
Wernicke–Korsakoff syndrome 406
Posner covert spatial attentional task 265
possession disorder 56possession states 276
possible foetal alcohol effects 1841
postcentral gyrus 146
postcentral sulcus 146
post-ejaculation refractory time 817, 822
postnatal depression 1122, 1486
and anorexia nervosa 780
counselling in 1280
effects on child development 1753

interpersonal psychotherapy 1322
and sleep deprivation in pregnancy 927
postpartum psychiatry 647, 653, 1121–5
Post-traumatic Stress Diagnostic scale 703post-traumatic stress disorder (PTSD) 700–13
and acute stress reactions 693, 696
aetiology 696, 705–7, 707
amnesia in 404, 714
animal models 707
assessment instruments 703
behaviours that maintain the symptoms 706
biological factors 706–7
childhood and adolescence 237–8, 1728–31 ,
1741, 1744, 1759, 1784, 1851–2
classiﬁ  cation 693, 701, 702–3
clinical features 701
cognitive content 1287comorbidity 704–5
course and prognosis 707–8
diagnosis 701, 702–3 , 703
differential diagnosis 695, 701, 702–3 , 703
epidemiology 703–5ﬂ ashbacks in 404
following accidents 1109, 1110–11
following childbirth 1121
following surgery 1099

genetics 707and intellectual disability 1851–2
and juvenile delinquency 1949–50
malingered 1055
and pain 1030–1partial 704
and physical illness 1131
prevalence 704prevention 697, 698, 1109, 1279–80
in refugees 1495, 1497
risk factors 707
and sleep-wake disorders 927
subsyndromal 1110
treatment and management 708–10, 1295, 
1497, 1784
victims of burglary/robbery 1986
victims of criminal activity 1984, 1985
victims of rape/sexual assault 1986
victims of terrorism 1987
postural hypotension
and chronic fatigue syndrome 1038
drug-induced 1190, 1223, 1529
posturing 58, 58
poverty
and child mental health 1727–8

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022and conduct disorder 1659
and homelessness 1500
relationship with morbidity and 
mortality 278
PPG (penile plethysmography) 840, 1962, 1964
PPO (Preferred Provider Organization) 45
practice nurses 1486
Prader–Willi syndrome 1841
and affective psychosis 1826behavioural phenotype 1613, 1614, 1838, 
1844, 1851 , 1858
cognitive and psychiatric aspects 1838, 1844
genetics 213, 224, 229, 1844
prevalence 1844
Pragmatic Language Impairment 1713pragmatics, difﬁ  culties with 1711, 1713
prameha  981
Precaution Adoption model 1137
precentral gyrus 145
precentral sulcus 145
preconscious 294, 295
prediction errors 259predictive learning 258–9
prednisolone 1532
Preferred Provider Organization 45
prefrontal cortex
in conversion disorder 1013, 1013 ,1014
and declarative memory 253
dorsolateral
transcranial magnetic stimulation 1264
and working memory 254–5
and fear/anxiety 1667, 1667
lateral 146
medial 146

medial 146
ventral, in obsessive–compulsive 
disorder 1684
pregabalin 743, 1182, 1237pregnancy
adjustment to 1116
alcohol use disorders in 1117, 1448, 1614–15, 
1754, 1826, 1841
anxiety in 1117and attachment 1117
bipolar disorder in 677
and body dysmorphic disorder 1116
delusions of 1115
denial of 1116depression in 653, 1117, 1322
domestic violence during 1117
early, and offending 1910
and eating disorders 780, 784, 1118
ectopic 1119electroconvulsive therapy in 1117
factitious disorder in 1050, 1118
foetal abuse in 1117
and panic disorder 761–2
pharmacotherapy in
antidepressants 675, 677, 761–2, 1117, 1192
antiepileptic drugs 677
antipsychotics 677, 1118
anxiolytics 1117
benzodiazepines 762, 1117, 1180butyrophenones 1118
carbamazepine 1118, 1234
lamotrigine 1235

lithium 677, 1118, 1205phenothiazines 1117, 1118propranolol 1117topiramate 1236
valproate 1118, 1169, 1232
premarital 272
psychosis in 1118
sleep deprivation in 927
smoking in 1646
substance use disorders in 480, 480, 1117–18, 
and suicide 1116, 1119
surrogate 1115
termination see abortion
volatile substance abuse in 504see also  obstetric complications
prejudice and stigma 6
premenstrual tension/syndrome 1114
premotor cortex 145
prenatal exposure to alcohol 1841
pre-occipital sulcus 145
preparedness theory and phobias 745Preparing for the Drug Free Y ears 
programme 1790
presenilins 227, 339
Present State Examination 71, 269, 272, 523, 
534, 542
pre-speech 240
pre-supplementary area 245
prevalence 281, 1607
estimation 138–41
lifetime 215, 542
point 215, 542

534, 542
typical estimates 285, 285
prevention
alcohol use disorders 467–72 , 1448–9
Alzheimer’s disease 341
anorexia nervosa 796–7
autism 1640body dysmorphic disorder 1048
child abuse and neglect 1737–8, 1788
in childhood and adolescence 1606, 1609–11
chronic fatigue syndrome 1042
comparison with health promotion 1609conduct disorder 1663, 1788
Creutzfeldt–Jakob disease 358–9
cyclothymia/cyclothymic disorder 689
deliberate self-harm 972–6
delirium 331, 1533Down syndrome 1448
dysthymic disorder 686
epilepsy 1620
evidence-based 1608–9
foetal alcohol syndrome 1448HIV/AIDS 1447
indicated 1609, 1610
infectious diseases 1447
intellectual disability 1447–8, 1448 , 1834–5
iodine deﬁ  ciency 1448
mood disorders 1448, 1555–6, 1675–7
panic disorder 762
pervasive developmental disorders 1640

phenylketonuria 1448post-traumatic stress disorder 697, 698, 
1109, 1279–80
primary 1446–51 , 1598, 1609
responsibility for 1449–50, 1450
and public health 1606–7relapse 1448
research cycle 1608–9role of epidemiology 281schizophrenia 550, 589, 1448
schizotypal personality disorder 601
secondary 1446, 1598, 1609
selected 1609, 1610
social anxiety disorder 744
staff burnout 1449, 1449
suicide 969–78 , 1449, 1708–9, 1992
tertiary 1446, 1598, 1609
theoretical models 1608
three-level concept 1446
universal 1609, 1610
vascular dementia 381, 1447violent behaviour 1449
volatile substance abuse 505
Wernicke–Korsakoff syndrome 450, 1542
primary auditory cortex 146
primary care 1480–9
alcohol use disorder detection 1484assessment in 67
classiﬁ  cation in 1483–4

clinical presentation in 1482–3
counselling in 1280, 1485–6
elderly people 1518treatment 1322, 1476
elderly people 1482–3, 1518, 1584
epidemiology 1480–2, 1481 ,1482
hidden vs. conspicuous morbidity 1482
interface with secondary care 1486–7management of psychiatric disorder 
1485–6, 1485
mental health professionals 1485–6
mental health services 1486
panic disorder 753prevalence of personality disorders 884
prevalence of psychiatric disorder 1480–2, 
1480 ,1481 ,1482
psychiatric nurses in 1406
refugee clinics 1496social worker attachment 1411
somatization in 1482
training in mental health 1487–8
primary care mental health workers 1485
primary child mental health workers 1812
primary identiﬁ  cation 1344
primary motor cortex 145

primary somatic sensory cortex 146
primary visual cortex 152
primidone
priming 250, 254
primitive defensive operations 298–9
primitive idealization 298
principlism 31
prion disease 351–61
acquired 352, 354–6
clinical features 352–3
diagnosis 352–3, 353
inherited 352, 353, 356–8
pre-symptomatic and antenatal testing 358
prevention 358–9
prognosis and treatment 359
species barrier/transmission barrier 352sporadic 352, 353
subclinical infection 352

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022prion protein 351, 353–4
prisoners
attention-deﬁ  cit hyperactivity disorder 1931
bipolar disorder 1934
depression 1923, 1933
elderly 1584
female 1934, 1935
Integrated Drug Treatment System 515
mental disorder 1933–6
prevalence 1933–4, 1934
mental health services for 1934–5
obsessive–compulsive disorder 1934
personality disorder 1921, 1933, 1933
post-traumatic stress disorder 1934
prevalence of personality disorders 884–5
psychopathy 1921
psychoses 1933, 1933
risk of suicide 976
schizophrenia 1934, 1934
substance use disorders 480, 1934
see also  offenders
prisons, psychiatric nursing in 1404
Pritchard, J.C. 18–19
private symbolism 54
PRNP  gene 351, 352–3, 357
mutations 357–8, 357
probability 1997
problem list 73, 74problem-solving therapy 1276
adjustment disorders 1068
conduct disorder 1781–2depression 1555
elderly people 1555, 1574
group setting 1351, 1352

procarbazine 1092
processing speed, assessment of 87–8, 88
prochlorperazine 1101
procyclidine 1225
Proﬁ le of Mood States 717
progesterone 816
progranulin gene/protein 348progressive multifocal leucoencephalopathy in 
HIV/AIDS 1093
progressive muscle relaxation in generalized 
anxiety disorder 736
progressive subcortical gliosis 348progressive supranuclear palsy 344
differential diagnosis 348, 364
Project Atlas 11
Project MATCH 452, 455, 456, 462projection 294, 299, 307, 1339
projective identiﬁ  cation 298–9, 307–8, 316, 
1339, 1340, 1344, 1770
projective techniques in child and adolescent 
prolactin 165–6, 815
in electroconvulsive therapy 1257hyperprolactinaemia 815, 826, 1086, 
1217, 1223
and seizures 1078
and social bonding 888
prolonged grief disorder 726
promazine 1209

1217, 1223
proneurones 157, 158proopiomelanocortin 170propentofylline in vascular dementia 381property destruction in conduct disorder 1656
propofol
in conversion disorder 999
propranolol
in acute stress reactions 697
in panic disorder 757in pregnancy 1117
Prospective and Retrospective Memory 
Questionnaire 420
prospective longitudinal (cohort) studies 282, 
283, 541, 557, 568
prostate 817
Protection-Motivation Theory 1137protective factors 1607
protein kinase C 1201
proteins
glycosylation (glycation) 1508–9
post-synthetic modiﬁ  cation 1508–9
proton magnetic resonance spectroscopy see
magnetic resonance spectroscopy
protryptylene 670,1187 ,1189 ,1191 ,1196
PrP (prion protein) 351, 353–4
PSE (Present State Examination) 71, 269, 272, 
523, 534, 542

pseudocorrelation 1608
pseudocyesis 1115
pseudodementia 335, 1551, 1551
in HIV/AIDS 385
treatment 1253
pseudohallucination 49
pseudologia fantastica (pathological lying) 
54, 871, 1049, 1051, 1941
pseudoneurasthenias 1060
pseudoseizures 1078, 1619, 1861pseudosexuality 869
pseudo-status 1050
psilocin 488
psilocybin 488, 489
psoriasis in alcohol use disorders 446Psychiatric Assessment Schedule for Adults with 
Developmental Disorders 1823
psychiatric disorder/psychiatric illness see
psychiatric injury 1902–3
psychiatric nurses 1403–7
community 462, 1404–5
in the developing world 1406–7
global survey 12, 12
in inpatient settings 1404
prescribing and medication 
management 1405–6
in primary care 1406
in prison settings 1404
provision of cognitive-behaviour 
therapy 1406

psychosocial interventions in the 
community 1404–5
psychiatric services see mental health services
Psychiatric Status Schedule 71
psychiatrists
cooperation with GPs 67
GPs’ expectations of 1486–7
as managers 39–46
in the multi-disciplinary team 68role in rehabilitation 1400psychic determinism 314
psychic retreat 308
PSYCHLOPS 1274Psych-Med unit 1145
psychoanalysis 293–305 , 1327, 1337–50
abstinence in 1339aspects of 293constructivist 299contemporary techniques 299–300, 1339–40defence mechanisms 293–4, 1339–40deﬁ nitions 293, 297
derived treatment modalities 300–1
efﬁ cacy 1345–6
ending treatment 1345
formulation 1341–2
history of therapeutic approach 23, 1338–9
indications and contraindications 301, 1341
interpersonal 310
interpretation in 1344–5
modes of therapeutic action 1340–1

and object-relations theory 297, 301–3, 
306–12
objectivist 299
outcome research 303–4
personality disorders 892
principal features of techniques 1339–41and psychopathology 296–7
and regression in 297, 1342
relational 1337, 1340
resistance to 1342
selection procedures 1341starting treatment 1341–2
supportive and directive interventions 1342
theories 293–6, 1337–8
therapist neutrality 1339, 1340
training in 1346
treatment duration 1327, 1341
treatment formulation 297
treatment management 1341–5
treatment process 297–8see also  psychodynamic psychiatry
psychoanalytic psychotherapy 300
indications and contraindications 301
psychodrama groups 1351, 1353psychodynamic counselling 1275, 1277–8
psychodynamic psychiatry 313–20

basic principles 313–15, 313
and conversion disorder 1011and countertransference 314, 315,
317–18
deﬁ nition 313
developmental orientation 314
future directions 319history of 23
and the mind–brain interface 315–16
multiple-treater settings 317
and personality development 316–17and pharmacotherapy 317
and psychic determinism 314
and somatization disorder 1004
and transference 314two-person concept 317–18
and the unconscious 313–14and the uniqueness of the individual 314

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022psychodynamic psychotherapy 313, 1327, 1337
avoidant personality disorder 897
borderline personality disorder 318–19, 894
brief (short-term) 318, 1327–37
background 1327comparison with interpersonal 
psychotherapy and cognitive-behaviour therapy 1333–4, 1333
comparison of therapies 1329–33
in conjunction with 
pharmacotherapy 1329
duration of treatment 1330
efﬁ cacy 1334–5
evaluation and setting 1327–8focus of 1329
practical problems in 1334, 1334
research 1334–5
schizotypal personality disorder 898
technique 1328–9
childhood and adolescence 1769–77
indications and contraindications 1772
limitations 1774
procedure selection 1772psychodynamic technique 1771–2
trauma 1730
deﬁ nition 318
expressive–supportive continuum 318, 1327

in intellectual disability 1874–5
long-term 318–19, 1327, 1329, 1338, 1345
see also  psychoanalysis
post-traumatic stress disorder 709schizophrenia 583
in sexual abuse by children/adolescents 1953
psychoeducation 1276
in anxiety disorders 735–6
disorder 1648–9
in bereavement 726
in borderline personality disorder 868
in cyclothymia 689in dementia 386, 411, 414, 418
in family therapy 1382
group setting 1351, 1352, 1364
in hyperthymia 691
in interpersonal psychotherapy 1321in manual-assisted cognitive treatment 895
in mood disorder 676, 677, 1554
in childhood and adolescence 1676, 1677
in psychodynamic child psychotherapy 1771, 
1773
in schizophrenia 583, 1448
in somatization disorder 1008

1773
in systems training for emotional 
predictability and problem solving 895
use by psychiatric nurses 1405, 1406
psychogeriatric services see mental health 
services, for elderly people
psychological anthropology 276
psychological ﬁ  rst aid 726
Psychological Impairments Rating Scale 72psychological pillow 58
psychological refractory period 248
psychologists, global survey 12, 12
Psychology of Criminal Conduct 2011
psychometric tests 81–2, 81, 85–7
clinical value 84in hypersomnia 939
sex offenders 1962
psychomotor acceleration 55
psychomotor agitation 58
psychomotor development, history-taking 1600
psychomotor retardation 55, 58
psychoneuroendocrinology 161
psychoneuroimmunology 205–11 , 1039, 1249
early investigations 205–6
effects of stress on immune system 205, 207, 
1135–6

1135–6
immune modulation of emotion and 
mood 209
immune system as sensory organ 207, 209
neural inﬂ  uences on immune system 206–7
receptors in the immune system 206
psycho-oncology 1100–5
Psychopathia Sexualis  (Krafft-Ebing) 836
and attachment theory 243
culture-related variations 982–3deﬁ nition 47
descriptive 47
distinction between form and content 48, 63
distinction between process and 
development 48
dualism in 848
explanatory 47
phenomenological 47–61
and psychiatric diagnosis 989
and psychoanalysis 296–7
psychopathy
in childhood and adolescence 1950
diagnosis 1921
in offenders/prisoners 1921–2
prediction of 851
Psychopathy Check List-Revised 1921, 2011
psychopharmacology, cosmetic 28–9
psychoprophylactics 1448
psychoses
acute and transient disorders 602–8

psychoses
in alcohol withdrawal 58, 443, 449–50, 538
cognitive model 1314
cycloid 574, 603, 605, 1124
and delirium 327
differential diagnosis 536–9, 1004
drug-induced
cannabis 507, 538
differential diagnosis 538–9
hallucinogens 489
phencyclidine 487prescribed medication 539stimulants 485, 498elderly people 1518–19
factitious 1055
ﬁ rst episode 573, 1396
following head injury 392–3
and intellectual disability 1826, 1827, 1854
malingered 1055menstrual 1114

monosymptomatic hypochondriacal 617–19
paranoid 392–3, 485
and physical illness 546, 1132
postabortion 1119
postpartum 647, 1124
prisoners 1933, 1933
psychogenic 603puerperal 1114
reactive 574
schizophreniform 536, 603, 605
secondary to organic disorder 537–8
and surgery 1098treatment 1254–5
very-late-onset schizophrenia-like 1518–19
psychosexual development 235
hormonal inﬂ  uences 1720
variation in 1718–19
psychosocial functioning
assessment 73, 1164, 1593
psychosocial interventions in dementia 414, 
414
psychosocial vulnerability and depression 271psychostimulants
psychosurgery see neurosurgery for mental 
disorder

414
disorder
childhood and adolescence 1764–9 ,
1769–77
differences from adult 
psychotherapy 1765, 1765
ending 1768
failure to attend 1768
individual vs. group therapy 1768involvement of parents and school 1768
limit-setting vs. free expression 1767
record-keeping 1768training and supervision 1768–9
comparisons with pharmacotherapy 1162
and counselling 1273–4, 1765
empirically supported 672

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022psychotherapy ( cont.)
evaluation 1158–67
internal vs. external validity 1159
measurement of therapeutic change 1163–4
outcome assessment strategies 1163
patient selection 1163
research design 1161–5
research planning 1159, 1160
selection criteria for outcome studies 
1159, 1161
treatment standardization 1161, 1161
in the paraphilias 838–9
personality disorders 892–901
process-orientated/outcome-orientated 672
treatment manuals 1161
see also speciﬁ  c therapies
psychoticism  81, 81
PTSD see post-traumatic stress disorder
PTSD Checklist 703
puberty, delayed/arrested in anorexia 
nervosa 787, 794
public attitudes and stigma 5–9
public health
epidemiology 1607–8
and prevention 1606–7
psychiatric disorder as worldwide issue 10–13
public policy
inﬂ uence on mental health 1426, 1426
see also  mental health public policy
publication bias 229
Pueraria lobata  1249

puerarin 1249puerperal psychosis 1124
puerperium
anxiety disorders in 1121
depression in 1122, 1280, 1322, 1486
normal 1120–1obsessive–compulsive disorder in 1121–2
Puerto Rican syndrome 983–4
pulmonary embolism 1082–3
pulmonary oedema in anorexia nervosa 785
pulse rate and conduct disorder 1658pulvinar sign 356
punch-drunk syndrome 395
puppets 1778
pure agraphia 54
purines 168
Purkinje cells 158
putamen 154, 159, 1684
Putnam, Hilary 134
pyramidal cells 148
pyramidal tract 156, 158pyrazinamide 1094
pyromania 914–15 , 1924, 1965, 1967, 1968
Q fever 1038
QALYs (Quality-Adjusted Life Y ears) 
124, 1475, 1510
quality of life
in alcohol use disorders 463
assessment instruments 73, 1165in body dysmorphic disorder 1044

quality management 43–4, 44
quasi-experimental studies 1468
querulant reactions to childbirth 1121querulous behaviour 616, 1977–80assessment 1978–9, 1979
clinical features 1977–8
management 1979–80
questionable dementia see mild cognitive 
questionnaires 62, 94–8
administration methods 95–6
content and format 95, 95
in epidemiology 284
forced-choice questions 94
reasons for development 69
self-report measures 94
standard vs. individualized 97
see also  assessment instruments
quetiapine 1199, 1209, 1209
administration 1214 , 1218

in childhood and adolescence 1677, 1797pharmacodynamics 1210, 1211 , 1213
pharmacokinetics 1221–2
quinacrine 359
quinalbarbitone 1178
rachischisis 156
racism, institutional 276
RAD (reactive attachment disorder) 243, 1590, 
1639, 1645
‘railway spine syndrome’ 700, 1902random sampling 139
randomized controlled trials (RCTs) 123, 1158, 
1466–8, 1608
advantages 1151–2, 1467
appraisal 126, 127–8biases 1151–2
blinding 127
cluster 1470
comparative designs 1162
concealment of treatment allocation 127control groups 1162
criteria for quality evaluation 1467
design and analysis 141–2
differential drop-out 128
dismantling designs 1162effectiveness 1466–8, 1468 , 1469–70, 1469
efﬁ cacy 1466–8, 1468
generalizability 1152
inapplicable situations 1467
inclusion and exclusion criteria 128
intention-to-treat analysis 128

limitations/disadvantages 1151–2, 1467
power calculation 1151
preference 1470
psychotherapy 1162–3
rogue results 1152systematic reviews see systematic reviews
validity 127–8
rape 1498
crisis centres 1988
date 409, 491
deﬁ nition 1985
offenders 1961victims 1985–6
raphe nuclei 150–1Rapid Risk Assessment of Sex Offender 
Recidivism 1963
rapid tranquillization 1404
in childhood and adolescence 1798
rapists, personality disorder 1921Ras proteins 175Rasmussen syndrome type 2 1864, 1867
Rat Man 1683
rate of living and longevity 1508rating scales/schedules 62, 94–8
reasons for development 69standard vs. individualized 97
rational emotive therapy in intellectual

rational emotive therapy in intellectual 
rationalization 294
Rauvolﬁ
 a serpentina  (rauwolﬁ  a) 1249, 1250
Raven’s Progressive Matrices T est 
87, 264, 1909
RBD see REM sleep behaviour disorder
RC (residential continuum) 1400
RCTs see randomized controlled trials
RDC (Research Diagnostic Criteria) 100, 523, 
534, 751
reaction formation 294
reactive attachment disorder 243, 1590, 
1639, 1645
reactive oxygen species, role in ageing 1509
reactivity 95
Read codes 1484
reading disorder 1627–9
reality orientation in dementia 414
reality principle 294, 295
reassurance, in medical consultations 1138
reassurance-seeking, in hypochondriasis 1022re-bonding 1514
reboxetine 670, 670
receptive language disorder 1626

reciprocity negotiation 1375
Recognition Memory T est 89
recovered memories 714–15, 834
recovery model 1491recreational drugs
classiﬁ  cation 1927
use by elderly people 1544
see also  substance use disorders and
speciﬁ  c drugs
reductionism 134
reduplicative paramnesia 392Reelin 158
refeeding 795
complications 786
referential thinking in body dysmorphic 
disorder 1044
reﬂ ective awareness 308
reﬂ ex sympathetic dystrophy 1015, 1050
reﬂ exive function 310

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022refugees 1493–500
assessment 1496–7
conceptual outcome models 1494–5, 1495
cultural factors 1496, 1496 , 1498
deﬁ nition 1493–4, 1493
depression 1495
families 1497
head injury 1495
health status and physical illness 1495internally displaced 1493
long-term functional impairment and 
disability 1495–6
post-traumatic stress disorder 1495, 1497
principle of non-refoulement 1493 , 1494
protection of 1493–4
psychiatric symptoms and illness 1495–6risk and resiliency factors 1498
screening 1496–7
somatic complaints 1497
torture 1494, 1495
trauma 1494–6, 1495 , 1496–7, 1497
treatment 1497–8
Regional Care Services Improvement 
Partnership Development Centres 1488
regression
as coping strategy 1066
in psychoanalysis 297, 1342
regressive transference neurosis 297–8rehabilitation 1352, 1399–403
in community mental health services 
389–90, 1459
core elements 1402
current approaches 1400–2development of environmental 
resources 1402

and family intervention 1401
and participation in the community 1402
role of psychiatrist 1400social skills training 583, 898, 1401, 1968
target population 1399–400
vocational 583, 1400–1, 1889
reinforcer devaluation 258
Relate 1370relationship counselling 1278–9
relative risk 126, 128, 282
relaxation techniques
applied relaxation 746
in insomnia 937in persistent somatoform pain disorder 1034
progressive muscle relaxation 736
in sleep disorders 1572
reliability 85, 92, 95, 137–8
in classiﬁ  cation in childhood and 
adolescence 1591
inter-rater/inter-observer 85, 95, 263, 1465
models and deﬁ  nitions 137–8
of outcome measures 1465parallel-form 85, 1465
split-half 85, 1465
test–retest 85, 263, 1465
types 85
religious delusions 51
religious healing ceremonies 1419–20
REM-atonia 946
REM latency 684, 931

types 85
REM sleep behaviour disorder (RBD) 928, 
946–7 , 1695
association with psychiatric disorders and 
stress 947clinical and polysomnographic ﬁ  ndings 
946–7
in dementia 416–17
diagnosis 947
in elderly people 1572in narcolepsy with cataplexy 941overlap with other parasomnias 947
treatment 947
reminiscence therapy 414, 1574
remoxipride 1209–10
repetition compulsion 299
repetitive self-mutilation 916–17
repetitive transcranial magnetic stimulation see
transcranial magnetic stimulation
reports 74–6
and conﬁ  dentiality 75
expert witness 1928, 2004 ,2005–6
partiality 75
principles 75
purposes 75
structure 75–6
repression 294
RERAs (respiratory effort-related arousals) 940
Rescorla–Wagner learning rule 259
rescue workers, debrieﬁ  ng 1110
research
on aetiology 281–6
on art therapy 1416

research
in epidemiology of child and adolescent 
psychiatric disorder 1597–8
1465–9, 1465 ,1466 ,1467 ,1468 ,1469
and evidence-based medicine 122–8
longitudinal 1597
on mental health services 281, 1452
study design 282, 1161–3, 1465–9, 1465 ,
1466 ,1467 ,1468 ,1469 , 1475–6
using with individual patients 126–8
Research Diagnostic Criteria 100, 523, 534, 751
reserpine 1172, 1249
residential continuum 1400
residential services
in childhood and adolescence 1799–802
in community mental health services 1453–4
for elderly people 1518, 1583
for people with intellectual disability and 
psychiatric disorder 1889
resilience 1607
and adoption/foster care 1748
in childhood 1660, 1803
of refugees 1498
in adolescence 1603–4

to psychoanalysis 1342
in psychodynamic psychiatry 297, 315, 317
repression 1342transference 1342
resistance to change in autism 1633
respiratory effort-related arousals 940
respiratory perturbation and anxiety 
disorders 1667
respiratory system
in anorexia nervosa 785in chronic fatigue syndrome 1038
disorders 932, 1082–3
respite care
in community mental health services 1458for elderly people 1583response inhibition/prevention 249, 1047
responsibility
criminal 1945, 1954
diminished 1901, 1922, 1923, 1928, 1937, 
1939, 1940
legal aspects 1900–5
see also  diminished responsibility defence
restless legs syndrome 948, 1572, 1695
restraint 1133, 1404
restriction fragment length polymorphisms 218
Rethink 1490–1
reticular nucleus 150

retiﬁ sm 833
retinal development 157retirement 1514
Retreat, Y ork 17–18
Rett’s syndrome 1614, 1636–7 , 1698
aetiology 1637
behavioural and psychiatric aspects 1845
clinical features 1636course 1637–8
deﬁ nition 1636, 1636
demographics 1636
epidemiology 1636
and epilepsy 1864, 1864–5
genetics 224, 229, 1637, 1844, 1866
management 1640physical characteristics 1845
prognosis 1637–8
revenge and ﬁ  re-raising 1967
reverse bonding 1514
reversed role play 1376
reversible inhibitors of monoamine oxidase 
(RIMAs) 670, 670
pharmacodynamics 1173
reviews 1152
and clinical assessment 74
‘reward deﬁ  ciency syndrome’ hypothesis 434
reward-dependence 80, 80, 316, 316, 849
Rey 15-item test 1057
Rey Auditory-Verbal Learning T est 89, 264

Rey–Osterrieth Complex Figure T est 89
Reynolds Adolescent Depression Scale 1675rhombencephalon 156, 157
rhombomeres 157
rhythmic movement disorder, sleep-related 
928, 1702
ribonucleic acid see RNA
rifampicin
RIMAs see reversible inhibitors of monoamine 
oxidase
rimonabant 513
risk 1991–2
individual, application of population data 281
modelling patterns of 141
risk analysis 44
risk assessment 1991–2
contemporary approaches 1992–3and contingency plan 1455, 1457
and culture of blame 1991–2
in dementia 417, 417
and expert witnesses 2005
limits of mental health professionals’ 
engagement 1993–4

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022risk assessment ( cont.)
offenders using drugs/alcohol 1927
violence 1991–2002
approaches 1994–5
by stalkers 1972–4, 1973
evaluating levels of risk 1998–9
instruments 1994, 1996–7
practicalities 1997–2000
utility 1995–6
risk difference 128
risk factors 1607–8
Alzheimer’s disease 1520–2, 1520 ,1522
anorexia nervosa 806
antisocial behaviour by adolescents 1946 , 1947
bipolar disorder 646–7, 1675
bulimia nervosa 805–6, 806
causative 1607
disorders 556, 1590, 1675
conduct disorder 1658–60
delirium 329, 329
dementia 376, 1520–2, 1520 ,1522
depression 648–9, 658–9, 1675
ﬁ xed 1607
hypochondriasis 997, 1024
independent 1608
malleable 1607
mania 646–7
mediating 1608
moderating 1608
offending 1909–14
overlapping 1608
panic disorder 753
post-traumatic stress disorder 707
proxy 1608
and refugee vulnerability 1498
schizophrenia 547–9, 553–61
sleep-wake disorders 1696–7
suicide 951–2, 953, 971, 971,972, 1449

proxy 1608
Risk for Sexual Violence Protocol 1998
risk management 44
of violence towards others 1997–8, 
1999–2000, 1999
risk-taking, morbid 921
risperidone 1209, 1209
administration 1214 , 1216–17
in bipolar disorder, in elderly people 1556
mania 1677with psychiatric/behaviour disorder and 
in delirium 331
in HIV/AIDS 1092in intellectual disability 1875
long-acting injectable 581
pharmacodynamics 1172, 1210, 1211 , 1213
in schizotypal personality disorder 600
in tic disorders 1688
Ritalin® see methylphenidate
rivastigmine

in dementia 415in Parkinson’s disease 370–1in vascular dementia 381
Rivermead Behavioural Memory T est 89
Rivers, W.H.R. 276RLS (restless leg syndrome) 948, 1572, 1695
RNA
double-stranded (dsRNA) 225
messenger (mRNA) 224–5, 224
micro (miRNA) 225
non-coding 229small interfering (siRNA) 225
road trafﬁ  c accidents see accidents
robbery, victims 1986
ROC curve 140, 1995
Rochester Y outh Development Study 1910, 1913
rofecoxib in Alzheimer’s disease 1538
Rogers, Carl 1273, 1274, 1276
Rohypnol (ﬂ  unitrazepam) 409, 491, 1183, 1188
ROI morphometry 195
role play, reversed 1376
role reversal 308
role theory and transitions 1514rolipram 176
ROM (routine outcome measures) 1460
ROS (reactive oxygen species), role in 
Rosenberg Self-Esteem Scale 1164

Rough Sleepers Initiative 1501
routine outcome measures 1460RRASOR (Rapid Risk Assessment of Sex 
Offender Recidivism) 1963
RSVP (Risk for Sexual Violence Protocol) 1998
rTMS see transcranial magnetic stimulation
genetics 1845
physical characteristics 1845
prevalence 1845
Rule Shift Cards T est 90
rule violation in conduct disorder 1656
‘rum ﬁ  ts’ 443
rumination
in anxiety disorders 1288–9
Russell’s sign 804
Russia, neurasthenia as diagnostic entity 1061Ryle, Gilbert 133
S-100b 353
S-adenosylmethionine 1248
sacriﬁ  cial ritual 1419
SAD see seasonal affective disorder; separation 
anxiety disorder
sadism 832–3, 833
criminal 832sexual 832, 836
sadistic personality disorder 878, 1921
sadomasochism 832–3, 878

SAFE Children (Schools and Families Educating 
Children) programme 1789
safety behaviours
in anxiety disorders 1287–8, 1288 , 1290
sage 1248St John’s wort 386, 686, 1248, 1250 , 1262
salivary gland enlargement in bulimia 
nervosa 804
Salpêtrière asylum 17, 18
Salvia divinorum  488Salvia ofﬁ  cinalis  1248
SAMe ( S-adenosylmethionine) 1248
sample bias 282–3
sampling 96–7, 138–9, 1595
principles 282–3structural MRI studies 194
Sanﬁ  llipo syndrome 1843
SARA (Spousal Assault Risk Assessment) 1998SARCs (Sexual Assault Referral Centres) 1986
SASB (Structural Analysis of Social 
Behavior) 852
satiety cascade 782SATs (Standard Assessment T ests) 1715Scale for the Assessment of Negative 
Symptoms 69, 72, 524
Scale for the Assessment of Positive 
Symptoms 524

SCAN (Schedules for Clinical Assessment in 
Neuropsychiatry) 70, 71, 72, 284, 542, 719
scapegoating 317
Schedule for Affective Disorders and 
Schizophrenia 70, 71, 523
Personality 858, 858
Schedules for Clinical Assessment in 
Neuropsychiatry 70, 71, 72, 284, 542, 719
schema-coping behaviour 895
schema-focused therapy 894, 895, 904, 1778
Schie syndrome 1843
schizoaffective disorder 595–602
classiﬁ  cation 596–7
clinical features 595–6
course and outcome 574, 596–7
diagnosis 597–8
differential diagnosis 537, 597–8elderly people 1552
epidemiology 598
family studies 596
management 598–9
premorbid function 595subtypes 597
schizoid personality disorder 862–3
aetiology 862
classiﬁ  cation 856, 863, 863
clinical features 863course 863
differential diagnosis 862, 863, 865, 876

epidemiology 862, 882, 882
treatment 863
schizoid thought 308
admission policies 585
and age 544–5
age of onset 558, 1547
atypical/unsystematic 574
catatonic 535
cerebral atrophy in 536
childhood and adolescence 1613
differential diagnosis 1673risk factors for development 556–7
classiﬁ  cation 535–6 , 1546–7
clinical features 526–31
anxiety and somatoform disorders 530
emotional disorders 529
motor disorders 529
thought and perception disorders 526–8
volition disorders 529–30
cognitive impairment 93, 265, 528, 
531–4 , 580

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022comorbidity
physical disease 546
substance use disorders 427, 507, 546, 
558, 1919
coping strategies 1313–14
course and outcome 536,568–78
deﬁ nitions and assessment of 
variables 569
elderly people 1548methodological factors 568–74
patterns and stages 571
predictors 574–6, 575
and risk factors 558
study results 569, 570
cultural and geographic variations 14, 546, 
557, 571–3, 572
delusions 526–7
depression in 529, 573
developmental antecedents 548
diagnosis and diagnostic criteria 103–4, 105, 
522–3, 534–6 ,535, 1547
diagnostic process 539
early diagnosis 536
and epidemiology 541inﬂ uence on outcome studies 568–9
differential diagnosis 327, 328, 536–9, 863, 
864, 1547
dimensions of psychopathology 530, 530
disease and disability burden 546–7disease expectancy/morbid risk 544
as a disorder of brain maturation 180–1, 
180,181
elderly people 1546–50 , 1552
aetiology 1548classiﬁ  cation 1546–7

180,181
differential diagnosis 1547, 1559epidemiology 1547
treatment and management 1548–9
emergencies 590
epidemiology 540–53
case ﬁ  nding 541
descriptive 542–7
in elderly people 1547
future issues 549–50
historical landmarks 540
incidence 542–4, 544,545
methods and instruments 541–2
prevalence 542, 543
ethnic minorities 549, 557–8
and expressed emotion 575, 583
family factors 536, 548–9, 553–5
and fertility 545and ﬁ  re-raising 1967
ﬁ rst-rank (Schneiderian) symptoms 523, 
526, 527–8, 527, 535–6, 573–4
and gender 544–5genetics 547, 548–9, 553–5, 565–6, 565
hallucinations 527, 573–4
hebephrenic (disorganized) 535, 574
history of concept 521–6
homicide by people with 1939, 1995
insight in 528

and intellectual disability 1827, 1854
and juvenile delinquency 1950late-onset 1547
markers 536
mental health services 584–5
models
genetic 554
gene–environment interaction 558–9stress–diathesis 507, 558–9, 1313
mortality associated 545–6
name change in Japan 7
and narcolepsy 927
natural history 569–70
negative symptoms 535
concept of 522, 523–5
dimensions 530
treatment 580, 589, 1265, 1548
neurobiology 561–8
functional 561–3
structural 563–4
theories based on 564–6, 565,566
neuropathology 178–81, 178,179,180,181
neuropsychological assessment 93, 265, 528, 
531–4
and obsessive–compulsive disorder 766
and offending 1918–20
and optical distortions 49
overlap with bipolar disorder for 
paranoid 535, 574, 609, 610
parental, effects on child development 1753

PET/SPET imaging 188–9, 562–3
positive symptoms 523
concept of 523–5
drug therapy 579–80
and pregnancy/birth complications 548premorbid intelligence 548
premorbid personality 536
premorbid social impairment 548
prevention 550, 589, 1448
prisoners 1934, 1934
prodrome 573, 589–90
pseudoneurotic 875
pseudopsychopathic 866
and pulmonary embolism 1083
recovery 576relapse 581
remission 589
residual 535
risk factors 547–9, 553–61
and age of onset 558birth season 547, 556
childhood 556–7
environmental 555–8
familial/genetic 547, 548–9, 553–5, 
565–6, 565
life events 558, 575
migration 286, 549, 557–8
model based on 558–9
obstetric complications 548, 555–6
and outcome 558paternal age 555
prenatal exposure to infection 547–8, 556
social and geographic 557–8
and sexuality 825–6
simple 535, 574

and social class 549
and stigma 5, 6–7, 539
subtypes 534, 535, 549
prognosis 574and suicide 545–6, 956
and surgery 1098syndromes of symptoms 530, 530
systematic 574
treatment and management 578–95
acute phase 586–8
adjunctive medication 591–2
cognitive-behaviour therapy 582–3, 
1313–18
of cognitive impairment 533
drug therapy 579–82, 579, 585, 586–8, 586,
1213, 1215 , 1548
elderly people 1548–9
electroconvulsive therapy 1255
in emergencies 590family therapy 583–4group therapy 1364
maintenance 581–2, 589outline plan 587
poor response to 590–2
post-acute phase 588
principles 585, 586
psychodynamic psychotherapy 583
psychoeducation 583
research 592resistance to 582, 590–2
social skills training 583

type I 524, 535–6type II 524, 535–6
undifferentiated 535, 574
and violence 1919, 1999
risk assessment 1995
and working memory 255
schizophreniform psychosis 536, 603, 605
schizotaxia 599
schizotypal personality disorder 599–601 ,
863–5
classiﬁ  cation 103–4, 599–600, 856, 864, 864
clinical features 599, 864
cognitive impairment in 533
course 864
diagnosis 600
differential diagnosis 600, 862, 863, 864–5in elderly people 1562 , 1563
epidemiology 600, 864, 882, 883
prevention 601
terminology 856–7
treatment and management 600–1, 865, 898
schnauzkrampf  58
Schneider, Kurt 522–3, 526, 681, 682, 686
school nurse 1812
‘school phobia’ 1665
schools
child psychiatrist as consultant to 1811–16
establishing a school liaison service 1812–13
factors in offending 1913
in hospital 1815

schools
intervention strategies based in 1814–15involvement in psychotherapy 1768
problems associated with conduct 
disorder 1656, 1662
role in child mental health 1727
role in child protection 1814
special 1815
see also  education
Schools and Families Educating Children 
Schwartz, Emanuel 1354

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022SCID-II (Structured Clinical Interview for 
DSM-IV Personality Disorders) 858, 859
SCL-90-R 1164
scopolamine, effects on memory 409
scoptic syndrome 833
scoptophilia 833
scrapie 351screening
for alcohol use disorders in elderly 
people 1542
in consultation-liaison psychiatry 
1145–6, 1146
for domestic violence 1982
instruments 69
sculpting 1376
SCUs (specialized care units) 1583
SD (standard deviation) 86SEAL (Social and Emotional Aspects of 
Learning) 1814
Searles, Harold 310
season
and bipolar disorder 646–7
and depression 635
seasonal affective disorder (SAD) 927, 939, 
1260, 1261, 1262
course and outcome 668
treatment 671
seasonal rhythms 1260Seattle Social Development Project 1912–13
second messengers 175–6, 175, 1172
downstream signalling cascades 176
second somatic sensory cortex 146
Secure Children’s Homes 1945secure hospitals 2015, 2016–17
admission criteria 2018
Secure Needs Assessment Proﬁ  le 2018

Secure Training Centres 1945
levels 2017
physical 2016
procedural 2016relational 2016–17
treatment as 2017
sedatives see anxiolytics
segmental aneusomy syndromes 228
seizures
absence 204, 1077
in alcohol withdrawal 443, 449
classiﬁ  cation 1076–7, 1077 , 1862, 1863
deﬁ nition 1076
differential diagnosis of epileptic and 
psychogenic 1861, 1862
drug-induced 1223, 1795, 1795–6
exercise-induced 1861
factors provoking 1861focal 1862, 1863
generalized 1077, 1619, 1863
secondary 1862, 1863
iatrogenic 1078induction by transcranial magnetic 
myoclonic 1077
nocturnal 1702
partial 1077, 1619
complex 201, 1077, 1619, 1863 , 1864
simple 1861, 1863 , 1864primary generalized 1862, 1863

provoked 1078
psychogenic 1016–17, 1080, 1861, 1862 ,
1863 , 1864
threshold 204tonic–clonic 1077, 1863
treatment 1080
withdrawal 1861see also  epilepsy
selective eating 787
selective mutism 1639, 1714
Selective Reminding T est 253
selective serotonin reuptake inhibitors see SSRIs
selegiline
selenium 1248
self
disorders of 56and the ego 295
self-actualization 1276
self-awareness 82, 83
self-deception 1941
self-defeating personality disorder 877–8
self-directedness 80–1, 80, 83, 316, 849–50
self-esteem 311
in bulimia nervosa 804, 806
and chronic fatigue syndrome 1036
and defence mechanisms 317
and domestic violence 1982and the ego ideal 296

and vocational rehabilitation 1401
self-harm see deliberate self-harm
self-help groups 1449
self-help skills, in intellectual disability 1873
self-image, in adolescence 1604
self-mutilation, repetitive 916–17
self-objects 311self-psychology 313
and somatization disorder 1004–5
Self-Regulatory Model 1138, 1140–1
self-report scales 4, 94
self-representation 298, 302–3self-soothing 1694, 1698
self-states 903
self-structures 316
self-transcendence 80, 80, 83, 316, 850
Selves Questionnaire 1164SEM (standard error of measurement) 85
semantic–pragmatic disorder 1713
semen 817
semen-loss anxiety 606, 981
seminal vesicles 817
SENCO (special educational needs 
coordinator) 1812
sensate focus exercise 1569
sensory dysfunction in conversion 
disorder 1017
sensory-speciﬁ  c satiety 258
separating 5

separation anxiety
and intellectual disability 1851
and panic disorder 754
separation anxiety disorder (SAD)clinical presentation 1665
septohippocampal system, in generalized 
anxiety disorder 733, 733
serotonergic system and serotonin 
receptors 173, 174, 1171
action of antipsychotics on 1170, 1209, 
1210, 1211
action of anxiolytics on 1178
and aggressive/antisocial behaviour 
889, 1918
in autism 1636and chronic fatigue syndrome 1039
in depression 189, 660, 662, 1185, 1186
in childhood and adolescence 1675
genetics 652
and eating disorders 782, 806
effects of ecstasy 496in generalized anxiety disorder 733–4
knockout studies 231
and memory impairment 409

and neuroticism 887–8in obsessive–compulsive disorder 767, 
1683–4, 1684
PET/SPET imaging 186, 187, 189
and schizophrenia 562serotonin transporter 169, 170, 189, 221, 273, 
286, 658, 887, 1674
and sexual function 826
and substance use disorders 429in substance use disorders 429, 436
and suicide 955, 964–5, 970, 1705
and T ourette syndrome 1073
serotonin and noradrenaline reuptake 
inhibitors see SNRIs
serotonin supplementation 1248
serotonin syndrome 1173, 1176, 1192, 
1194, 1254
sertindole 1209
sertraline 670
in obsessive–compulsive disorder 1687, 1687

in social anxiety disorder 743, 744
SES see socio-economic status
Settlement Movement 1408
sex chromosomes 218, 223, 225
abnormalities 1840–1
sex-linked disorders 212
Sex Offender Risk Appraisal Guide 835, 1963
sex offenders 1960–4
assessment 1961–2
classiﬁ  cation 1960–1
deﬁ nitions 1960
ethical issues 1964
and the general psychiatrist 1960juvenile 1953–4

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022mood disorders 1923
personality disorder 1921
risk assessment 1963, 1963
treatment 1963–4
sex reassignment surgery 842, 843–4
sex therapy 821, 827–8 , 829
brain activation during 819
extragenital changes 815
female 816, 817–19
loss of 822male 816–17pain during 822
Sexual Assault Referral Centres 1986
sexual disinhibition in dementia 416
sexual dysfunction 821–32
aetiology 823–7
assessment 829–30
classiﬁ  cation 823
clinical features 822–3
deﬁ nitions and terminology 821–2
drug-induced 826–7, 1190
Dual Control Model 821, 824
in elderly people 1569, 1570
in end-stage renal disease 1087
epidemiology 823, 824
historical aspects 821–2and mental health 825–6
treatment and management 827–30, 1569–70
and epilepsy 1079and mental health 825–6
normal 812–20
biological determinants 812–13
DEOR model 814–15, 814
in elderly people 1569, 1569
endocrinology 815–16

EPOR model 814–15, 814
initiating activity 815
modelling 813–15
surveys 813–14, 821–2
sexual inhibition 825
Sexual Offences Act 1956 1899–900
Sexual Offences Act 2003 1900, 1985
sexual orientation, of elderly people 1568
sexual orientation disturbance, legitimacy of 
diagnosis 28
sexual scripting 813
Sexual Violence Risk-20 1998
sexuality
assessment in childhood and 
adolescence 1604
and dementia 1568
in elderly people 1567–70
and ﬁ  re-raising 1967
in Huntington’s disease 373and intellectual handicap 1873, 1879
psychoanalytic theories 294–5
as a social construct 813–15
sexually transmitted disease (STD) 1094
delusions concerning 619and stigma 1091
see also speciﬁ  c diseases
SF-12 284
SF-36 284
shabu (methamphetamine) 497–8
shamanism 1419shared care plans 1487shared care register 1487

SF-12 284
SF-36 284
shared psychotic disorder 610, 624–5
Shedler-Westen Assessment Procedure 858, 858
‘shell shock’ 700
shenjing shuairuo  1061
shift work and sleep disturbance 926
shin-byung  606
shinkeishitsu 1061
shoplifting 1923, 1924, 1943
short-term anxiety-provoking 
psychotherapy 1327, 1331–2
SIADH and ecstasy 495
sialidosis 1864, 1865Siberia, attitudes to psychiatric disorder 6
siblings
effects of loss of sibling 1120, 1759
effects of sibling with intellectual 
disability 1884–5
effects of sibling with physical illness 1742
sick role 1320, 1321sickness, concept of 62, 63–4
SIDS (sudden infant death syndrome) 
1119, 1698
siege experience 49–50
sign language
in autism 1639
in expressive language disorder 1626
in receptive language disorder 1626
signs, deﬁ  nition 47
sildenaﬁ  l 821, 828

1119, 1698
Silence of the Mind meditation 82simple phobia see speciﬁ  c phobia
simulated presence, in dementia 414
single-case studies 1161
single nucleotide polymorphisms 218, 226, 227
single-photon emission tomography (SPET/
SPECT) 185
comparison with functional magnetic 
comparison with PET 185data collection and analysis 186
depression 189, 660
during antipsychotic use 189–90
in epilepsy 1862frontotemporal dementias 347, Plate 12
limitations 186–7methodology 185
schizophrenia 188–9
Six Elements T est 265
skin
delusions concerning 50, 51, 618
effects of alcohol use disorders 446
skin picking, pathological/compulsive 618, 
917–18 , 1044

skin
Slavson, S.R. 1353sleep 924–6
active 946
architecture 925
changes with age 925–6, 1571–2
and chronic fatigue syndrome 1036, 1039circadian rhythms 925, 926
and depression, in childhood and 
deprivation, in the puerperium 1120functions 924–5
insufﬁ  cient 1700
nature of 924
non-rapid eye movement (NREM) 924, 925
paradoxical 946
physiology, in childhood and 
adolescence 1692–3
rapid eye movement (REM) 924, 925, 
946, 1694
requirements 1694
slow wave (SWS) 925, 1694stages 925
unihemispheric 925
sleep debt 1700
sleep diary 929, 934, 1696
sleep drunkenness 941
sleep education 936, 936
sleep efﬁ  ciency 936
sleep history 929, 1696
sleep hygiene 936, 936
sleep onset REM period 941
sleep paralysis 929, 940
sleep questionnaire 1696

sleep-related dissociative disorder 948
sleep-related eating disorder 931, 947–8
sleep-related injury 945
sleep-related rhythmic movement disorder 
928, 1702
sleep restriction therapy 936
sleep terrors 928, 945–6 , 1702
sleep-wake cycle, in delirium 326–7
sleep-wake disorders 924–33
in aetiology of psychiatric illness 927
and alcohol use disorders 931
and anxiety disorders 931
assessment 929–30
disorder 927, 931, 1695, 1697
audio–video recordings 929
and autism 1697and cardiovascular disease 932
childhood and adolescence 1693–702
1694–5
misinterpretation 1695parasomnias 1701–2
parental inﬂ  uences 1694

1694–5
sleeplessness 1698–9treatment and prognosis 1695–6
and chronic fatigue syndrome 1697
and chronic pain 932
and chronic renal failure 932
circadian rhythm 928
classiﬁ  cation 927, 928
and dementia 416–17, 931, 1572, 1573
and depression 634, 661–2, 927, 931, 
931, 1697
detection 929–30
and eating disorder 931

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022sleep-wake disorders ( cont.)
elderly people 1571–3
and endocrine disease 932
and epilepsy 932
following stroke 932
and gastrointestinal disorders 932
and head injury 932, 942, 1698
hypersomnia see hypersomnia
hypnotic-dependent 934insomnia see insomnia
and intellectual disability 926–7, 1694, 1697–8
in intensive care patients 932
and iron deﬁ  ciency 932
and mania 931
mistaken for primarily psychological/
psychiatric conditions 927–9
in neurological and physical illness 931, 932,
933, 941, 942
and obesity 932
and obsessive–compulsive disorder 1697
and panic disorder 1697
parasomnias see parasomnias
in Parkinson’s disease 932, 1072
postoperative 1099
and post-traumatic stress disorder 927
in psychiatric conditions 930–1, 931
psychological effects of sleep 
disturbance 926–7
REM sleep behaviour disorder 
928, 1572, 1695
and respiratory disease 932
and schizophrenia 931

sleep-related breathing disorders 928
sleep-related movement disorders 928, 1702
and substance use disorders 931
and tic disorders 1697
and T ourette syndrome 932, 1697
treatment approaches 930, 930
sleepiness, excessive daytime see hypersomnia
sleeplessness
in childhood and adolescence 1698–9
partial 926total 926
sleepwalking 928, 945–6 , 1702, 1930
SLI (Speciﬁ  c Language Impairment) 1710, 
1713–15
SLITRK1 gene 229
SLT see speech and language therapy
Sly syndrome 1843small G proteins 175
Smart, J.J.C. 134
smell, delusions of 618–19
behavioural phenotype 1845, 1851
psychiatric aspects 1845
smoking

smoking
by elderly people 1544
by psychiatric patients 511cessation treatments 511–13disease burden 510
genetic factors 510–11
and health 1136mortality associated 510
and nicotine dependence 510–15
in pregnancy 1646
prevalence 510
withdrawal symptoms 511
snake-handling cult 1419–20SNAP see Schedule for Nonadaptive and 
Adaptive Personality; Secure Needs 
Assessment Proﬁ  le
snoezelen therapy 414
snow (cocaine) 430
SNPs (single nucleotide polymorphisms) 
218, 226, 227
SNRIs 670, 670
adverse effects 674
in childhood and adolescence 1796in generalized anxiety disorder 735

Social Adjustment Scale 1165
social and cultural anthropology 14, 15, 275–9
Social and Emotional Aspects of Learning 1814
social anxiety disorder 739–44 , 1639
aetiology 741
and avoidant personality disorder 740, 897
childhood and adolescence 740, 1665, 1666
classiﬁ  cation 740–1
clinical presentation 740
comorbidity 740, 744
course 741
differential diagnosis 740–1, 752, 873epidemiology 741
functional impairment in 740
generalized/non-generalized 740
with panic disorder 750prevention 744
secondary to physical disorder 740
treatment and management 741–4
social bonding 888–9social capital 1610
social cognition models 1136–7, 1140–1
social communication, problems with 1711, 1713
social constructionism and ageing 1515
social development 242–3, 242

social drift 557
social inclusion 1819
social learning theory
social phobia see social anxiety disorder
Social Readjustment Rating Scale 1065
social role valorization 1409–10
social skills training 1401
antisocial personality disorder 898ﬁ re-raising 1968
social stress theory, and transitions 1514social suffering 848social support
and group therapy 1352in mood disorders 653and psychiatric disorder in intellectual 
and response to illness 1066
and suicide 954
social theory 277
social withdrawal in depression 634
social work 
see mental health social work
social workers
approved 1410
attachment to primary care 1411
socio-economic status (SES)

and anorexia nervosa 778and anxiety disorders 1666
and mood disorders 654
and offending 1912
and schizophrenia 549, 557
sociology of ageing 1512–16
sociometry 1353
sociosomatic processes 278
sodium oxybate 941
sodium valproate see valproate
Solution Oriented Schools 1814
solvent abuse see volatile substance abuse
somatic sensation, cortical association 
pathways 146, 152
somatization 57, 278, 989–90
by refugees 1497
in childhood and adolescence 1744, 1744
cultural inﬂ  uences 15
and pain 1030, 1031
presentation in primary care 1482
subthreshold 996, 998
and surgery 1096
somatization disorder 999–1011
abrupt onset 1002
aetiology 1004–5
assessment 1005–6, 1005–6

in childhood and adolescence 1744
and chronic fatigue syndrome 1037classiﬁ  cation 993, 994, 999–1000, 1003
clinical features 1000–2
physical symptoms 1000–2, 1001
psychological symptoms 1002
comorbidity 57, 870, 1002, 1004controversial aspects 996
correlates 996
course 1005
diagnosis 1003differential diagnosis 1003–4, 1023–4
dystonia in 1016
epidemiology 996, 1004
examination 1005–6
family transmission 1004and illness behaviour 1002
phenomenology 996
prevalence 996, 998, 1004
prognosis 1005TERM model 1005, 1008, 1008

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022treatment and management 1006–10, 1008 ,
1009 , 1034
somatoform autonomic dysfunction 993,
994, 1003, 1003–4
differential diagnosis 1030
somatoform disorders 57, 989–90
acute/chronic 1003
assessment 994–5, 995
classiﬁ  cation 104, 105, 993–4, 993, 999–1000, 
1003, 1023
comorbidity 57, 994, 1002, 1004
differential diagnosis 1050–1
epidemiology 995–9
mimicking surgical conditions 1096multisymptomatic 1003
and pain 1031–2
problems in deﬁ  nition 994
treatment 994–5, 995
undifferentiated/not otherwise speciﬁ  ed 993,
994, 1000, 1003, 1036, 1062
somatomedin C 165
somatosensory ampliﬁ  cation 1025
somatostatin 165, 171
somnophilia 833
SORAG (Sex Offender Risk Appraisal 
Guide) 835, 1963
sorcery, fear of 981SOREMP (sleep onset REM period) 941
SOS (Solution Oriented Schools) 1814
Soteria model 1393, 1396
South Africa, attitudes to psychiatric disorder 6

South Verona Outcome Study 1468–9soy 1249
spasm, in conversion disorder 1016
spatial cueing task 246
special educational needs, meeting 1815
special educational needs coordinator 1812Special K (ketamine) 489, 499–500 , 1186
specialized care units 1583
speciﬁ  c developmental disorders 1622–32
diagnosis 1623
differential diagnosis 1623 , 1639
mixed 1623
of motor function 1623, 1623 , 1631
of scholastic skills 1623, 1623 , 1627–31
of speech and language 1622–7, 1623
Speciﬁ  c Language Impairment 1710, 1713–15
speciﬁ  c phobia 52, 744–50
aetiology 745
age at onset/seeking treatment 745
in cancer 1101childhood and adolescence 1664, 1665, 1666, 
1741, 1742
classiﬁ  cation 745
clinical features 744–5
comorbidity 745course 745–6
differential diagnosis 766
epidemiology 745

1741, 1742
functional impairment in 744–5
and gender 745
of illness 52, 1022, 1023
prevention 746
subtypes 745
and surgical procedures 1097
treatment and management 746speciﬁ  c reading disorder 1627–9
speciﬁ  c speech articulation disorder 1624–5
speciﬁ  c spelling disorder 1629
speech and language development 240–1, 241,
1623, 1710–11
disorder 1714
in childhood and adolescence 1710–17
classiﬁ  cation 1711
course and prognosis 1715
deﬁ nitions 53
diagnosis and differential diagnosis 1712
disturbance in generation and articulation of 
words 53
disturbance in talking 53–4
due to sensory or CNS impairment 1623–4
expressive 1625–6
features of difﬁ  culties 1711

words 53
identiﬁ  cation 1715
and intellectual disability 1712
management 1715–16
and motility disorder 58organic language disorders 54
receptive 1626
in schizotypal personality disorder 864
1622–7 ,1624
speech and language therapy (SLT) 1714, 1716
expressive language disorder 1625–6
selective mutism 1714
speech articulation disorder 1624–5
speed see amphetamine
Speed of Comprehension T est 88
spelling disorder 1629
SPET see single-photon emission tomography
spider naevi in alcohol use disorders 446
spina biﬁ  da occulta 156
spinal cord
histogenesis 157–8
spinobulbar muscular atrophy 228
spinocerebellar ataxia 228
spinocerebellar degeneration 373
spiny stellate cells 148
spirit dancing ceremony 1419spirit mediumship 1418–19

splitting 295, 297, 298, 307, 317, 1339
Spousal Assault Risk Assessment 1998
Sprachverödung  346
SPT see supportive psychotherapy
SRM (Self-Regulatory Model) 1138, 1140–1
SRV (social role valorization) 1409–10
SSD 719
SSP (Strange Situation Procedure) 242
SSRIs 670, 670, 1178
in adjustment disorders 721, 1068
adverse effects 674, 1190, 1191 , 1687–8
aggression 1923
sexual dysfunction 826
sleep disorders 1572
suicidal ideation/behaviour 
1668, 1707–8, 1923
in childhood and adolescence 1668in attempted suicide 1707–8
in body dysmorphic disorder 1046, 1047–8
in cancer 1101–2, 1102, 1102 ,1103
1668, 1676, 1796
in chronic fatigue syndrome 1040

in conversion disorder 1019–20
in depression
in childhood and adolescence 1676in elderly people 1554, 1554
drug interactions 1175–6in dysthymia/dysthymic disorder 685in generalized anxiety disorder 735
in Huntington’s disease 374in hypochondriasis 1027
in obsessive–compulsive disorder 769–70, 
1687–8, 1688–9
in panic disorder 756, 756, 759
in the paraphilias 838
in persistent somatoform pain disorder 1034in personality disorders 905, 906
in premature ejaculation 828in smoking cessation 513
and suicide risk 674

SSRT (stop signal reaction time task) 266
staff burnout, prevention 1449, 1449
staff counselling services 1281–2
stages of change model 428
stalking 1917, 1970–6
assessment 1974
and attachment 1972
classiﬁ  cation and typology of stalkers 1971
deﬁ nition 1970
and delusional disorders 1920duration 1972
epidemiology 1970
of health professionals 1972
impact on victims 1970–1
management 1974as obsessive–compulsive disorder 1972
psychopathology 1971–2
reduction of impact on victim 1974risk assessment and management 
1972–4, 1973
risk of violence 1973–4, 1998
stammering 53
Standard Assessment T ests 1715standard deviation 86
standard error of measurement 85
standard score ( z) 86, 86
standardized interview schedules 14, 284
Stanford Acute Stress Reaction 
Questionnaire 695
starﬂ  ower 1248

startle-induced dissociative reaction 606, 983
startle response 732, 1667STATIC-99 1963, 1994, 1996, 1997, 1998

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022statistics 137–43
evaluating treatment effects 141–2
modelling patterns of risk 141
prevalence estimation 138–41
reliability of instruments 137–8
structural MRI studies 194–5, 196
systematic reviews 1155–6
status cataplecticus 940
status dissociatus 944
status epilepticus 1077
absence 1864
complex partial 1077
electrical 1864
in intellectual disability 1867treatment 1255, 1867
status loss 5
STD see sexually transmitted disease
stealing, pathological 913–14 , 1924, 1942–3
stem cells
adult, and study of ageing 1510
embryonic, recombination studies 230
step-families 1726–7
stepped-care model 1006–7
in adjustment disorders 1068, 1068
in anorexia nervosa 789
in primary care 1484, 1485
STEPPS (systems training for emotional 
predictability and problem solving) 895, 904
stereotyped behaviour in frontotemporal 
dementias 346
stereotypic movement disorder with intellectual 
disability 1683, 1851
stereotypy 5, 58, 58
sterilization 1115–16

stigma 5–9, 11, 1585
and chronic fatigue syndrome 1039–40
combating 1408
component processes 5
deﬁ nition 5
and dementia 411and electroconvulsive therapy 1251, 1258
global patterns of 6–7
limitations of work on 5–6
and neurasthenia 1040
and personality disorder 848and rehabilitation 1402
and schizophrenia 5, 6–7, 539
in sexually transmitted disease 1091
and suicide 953
still face paradigm 240stillbirth 1119
stimulants see speciﬁ  c drugs
stimulus-bound behaviour 58
stimulus control in sleep disorders 936, 1572
stimulus entrapment 1005
stop signal reaction time task 266
story telling 1778
STPP see psychodynamic psychotherapy, brief 
Strange Situation Procedure 242
strategic therapy 1381stratum pyramidale 148
Strengths and Difﬁ  culties questionnaires 1813

streptococcal infection
and obsessive–compulsive disorder 
1616–85
and tic disorders 1073, 1685streptomycin
stress
acute/chronic 720
and adjustment disorders 720
and ageing 1507, 1508
and anxiety disorders 1667–8
associated with inpatient care 1139–40
and counselling 1278
deﬁ nitions 1065
disorders induced by/related to 716
effects on immune system 205, 207, 1135–6
and health 1135–6
illness as 1065
and inﬂ  ammatory bowel disease 1083–4
and irritable bowel syndrome 1083
modiﬁ  ers 720
and myocardial ischaemia 1081–2
and REM sleep behaviour disorder 947
and somatization disorder 1009
transactional model 1065
and transient global amnesia 403and ventricular dysrhythmias 1081
see also  acute stress reactions
stress–diathesis model

personality disorders 851–2
schizophrenia 507, 558–9, 1313suicide 963–4, 965
stress management (stress inoculation), in 
‘stress response syndromes’ 717
stressors
in acute stress reactions 694
traumatic 701
stria of Gennari 146
stria terminalis, bed nucleus
in gender identity disorder 842in generalized anxiety disorder 733
striate cortex 146
striatum 154–5, 1684
stroke 1071–2
anxiety following 1071–2depression following 1071, 1555
emotionalism following 1071
sleep-wake disorders following 932
Stroop T est 90,248, 249, 255, 265
Structural Analysis of Social Behavior 852
structural magnetic resonance imaging (MRI) 
191–6
alcohol-related dementia 400–1
artefacts 193–4, Plate 7in chronic fatigue syndrome 1039
clinical data analysis 195

191–6
in conjunction with PET 187
sporadic/classical 353
variant 356
dementia with Lewy bodies 364diffusion-weighted imaging 193, Plate 8
epilepsy 1078, 1619, 1862, 1930
frontotemporal dementias 347
hardware 194
head injury 389HIV-associated dementia 385
Korsakoff syndrome 406mild cognitive impairment 1537–8morphometry 195, Plate 9
post-traumatic stress disorder 706quantitative data analysis 195–6, Plate 9
safety 193
scanner suite 194
schizophrenia 179–80, 179, 563–4
spin echo sequence 192, 192
structural imaging sequences 193
studies 194–5
tissue contrast 192–3, 193, Plate 7
vascular dementia 377, 380
Structured Clinical Interview for DSM-III and 
DSM-IV 70, 71, 695, 703, 1023, 1164

Personality Disorders 858, 859
Structured Interview of the Five-Factor Model 
of Personality 1164
structured interviewing see questionnaires
Structured Inventory of Malingered 
Symptoms 1057
student counselling services 1281
stupor 58, 58
Sturge–Weber syndrome 1867
stuttering 53, 1623, 1712subacute spongiform encephalopathies 
see prion disease
subarachnoid haemorrhage 407
subcaudate tractotomy 1267
subcultural deviance 1657subdural haemorrhage 387
subiculum 148
subjective experience, categorization of 48
sublimation 297
subsidiarity 1896
substance P 155, 170, 171,173, 206
substance use disorders
amphetamine 482–6
assessment instruments 1164childhood and adolescence 1600, 1604

comorbidity
disorder 427, 1650
bipolar disorder 646body dysmorphic disorder 1044
depression 649persistent somatoform pain disorder 1032
schizophrenia 427, 507, 546, 558, 1919
social anxiety disorder 427
somatization disorder 1002
and conditioning 428, 434effects on the brain 429–30, 429
elderly people 1519, 1540–6
genetics 428–9
global disease burden 10
hallucinogens 487–9and homicide 1926
and infection 430
inpatient care 1453legal issues 1927–8

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022motivation for 426–7
and offending 1926–8
and pain 427
parental, effects on child development 1754PCP 486–7
pharmacological aspects 426–32
in pregnancy 480, 480, 1117–18, 1614, 
1615–16, 1754
prisoners 480, 1934
psychological aspects 426–32
relapse prevention 428routes and risks of addiction 430–1, 431
services 515–20
commissioning 517–19
levels 516–17
local coordination 515–16
needs assessment 517, 518–19
performance analysis 519–20target groups 517–18
and suicide 955, 956, 1704
terminology 427–8
treatment
cognitive-behaviour therapy 428, 1784
counselling 1279
motivational interviewing 428outcome 519, 519
pharmacotherapy 1242–7
and stages off change model 428
tiered 516–17
and violence 1449, 1926
risk management 1999
substantia nigra 154

subthalamic nucleus 154subthreshold disorders 680–92 , 716, 718–19, 722
sucralfate 1175sudden infant death syndrome 1119, 1698
suffering 848
suicidal ideation 951, 952, 955
and antidepressants 971, 973, 1192, 1668, 
1707–8, 1796, 1923
in childhood and adolescence 1703
in parents 1923prevalence 960
provoking factors 961
see also  suicide
suicide
and adjustment disorders 718, 722
and aggression 970
and alcohol use disorders 427, 444, 955, 956
altruistic 954
anomic 954
and anorexia nervosa 955
and anxiety disorders 955
attempted see deliberate self-harm
biological aspects 963–9
and bipolar disorder 1704
by imitation (Werther effect) 952, 1706
by inpatients 1404
and cancer 1102–3

childhood and adolescence 1674, 1702–10and choice of antidepressants 670, 674, 
970–1, 1192
choice of method 952, 973
and conduct disorder 1704
cultural factors 953–4, 1704
deﬁ nition 951
and depression 634, 955, 1704
determinants 953–5, 954
education regarding 974
egoistic 954
elderly people 976, 1518, 1527, 1551, 1564–7
and electroconvulsive therapy 1255
epidemiology 951–7
and epilepsy 1080
ethical issues 30
extended 1923
family 981–2
fatalistic 954
following head injury 393
following homicide 1923, 1938
and gender 1704
genetics 954–5, 966–7
global statistics 10
and hypochondriasis 1026
and hypothalamic–pituitary–adrenal 
axis 965
and impulsivity 970
indirect 1565
and life events 954, 969, 1705
media portrayal of behaviour 974
and mental disorders 955–6, 955
modelling behaviour 963–4

axis 965
neurobiology 954–5, 966–7
 ‘no-suicide’ contracts 1707
and noradrenergic system 965
pacts 952, 1706and panic disorder 1704
and personality disorders 955, 956, 969
physician-assisted 318
and pregnancy 1116, 1119prevention 969–78 , 1449, 1708–9, 1992
and problem-solving 969
process 951–2, 952
protective factors 951–2
psychology of 954public health aspects 952–5
rates 952–3, 953
rational 30, 1565
reliability of statistics 951
risk after deliberate self-harm 961risk behaviours in childhood and 
adolescence 1605
risk factors 951–2, 953, 971, 971,972, 1449
role of internet 1706
and schizophrenia 545–6, 956
and self-esteem 970
and serotonergic system 955, 964–5, 970, 1705
and social support 954sociological theories 954
stigma of 953
stress–diathesis model 963–4, 965

and substance use disorders 955, 956, 1704and terminal illness 1070
victim characteristics 955
Sullivan, Harry Stack 310
sulphonamide 1091
sulpiride in tic disorders 1073, 1688sumatriptan 1171sundowning 336
suoyang  980
super K (ketamine) 489, 499–500 , 1186
superego 294, 296, 306, 313, 849superego defences 297
superior parietal lobe 245superior temporal sulcus 146supervisory attention system 249
supported employment 1401
supported housing 1400
supportive-expressive therapy, avoidant 
personality disorder 897
supportive psychotherapy (SPT) 300–1
borderline personality disorder 868
personality disorders 318–19
suprachiasmatic nucleus, and circadian 
rhythms 925, 1260

SureStart programme 1663
surgery 1096–100
assessment of response to 1097
capacity to consent to 1096–7
postoperative complications and 
interventions 1098–100
preoperative assessment and 
intervention 1096–8
transplantation 456, 1087, 1097see also  neurosurgery for mental disorder
surrogate motherhood 1115
surveys
in case-ﬁ  nding 541
design 139, 541
results analysis 139–40
survivor guilt 1106
susto  984
SVR-20 (Sexual Violence Risk-20) 1998
SWAN scale 1645
SWAP-200 1164
sweating in alcohol withdrawal 439
Sydenham’s chorea 767, 1685Sylvian ﬁ  ssure 144
sympathetic nervous system 156, 206
symptom validity tests in malingering 1057
symptoms
conversion 57, 1012–13
developmental differences in 
expression 1600
dissociative 1012–13

symptoms
effects on function 63
elaboration 57feigning 57
functional (without organic pathology/
medically unexplained) 989–90, 992, 999
aetiology 992–3
assessment and treatment principles 
994–5, 995
atypical nature 1001
classiﬁ  cation 993–4
descriptions 1001, 1001
and psychiatric disorder 993
terminology 992
measures of severity 1465
negative, assessment instruments 72
prodromal/subthreshold 1607

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022symptoms ( cont.)
psychology of 1137
subjective 1000
understanding of 47–8
syndrome of subjective doubles 623
syntax, problems with 1711
syphilis 1093–4
meningovascular 1093
systematic lupus erythematosus 1086–7
systematic reviews 123–4, 126, 1152–3, 
1466, 1466
advantages 1153
limitations 1153–4
methods 1154–6sources 1156–7
systems theory in family therapy 1381–2
systems training for emotional predictability 
and problem solving 895, 904
T helper cells and immune function 206
T3 (triiodothyronine) 163, 675, 784
T4 (thyroxine) 163, 1101
TA (transactional analysis) 1277
Tabernanthe iboga  488, 1249, 1250
tabes dorsalis 1093–4
tachycardia in alcohol withdrawal 448
tachykinin receptors 173
tachykinins 171, 171
tachyphasia 53
tacrine 1241
tadalaﬁ  l 828
taijinkyofushio  982
Taiwan, neurasthenia 1061
tandospirone 735, 1212
tangentiality 53
tanning, compulsive 1044
tardive dyskinesia 59

drug-induced 1223
tau protein 228
in Alzheimer’s disease 338, 339in dementia with Lewy bodies 362
in frontotemporal dementias 344, 347
tauopathies 338
Tavistock Clinic 1353, 1408
Tay-Sachs disease 1825, 1865
TDP-43 protein 348
TEACH (T ests of Everyday Attention for 
Children) 89
teachers
and schools liaison service 1813training in mental health 1812
technical eclecticism 1278
teeth, enamel erosion in bulimia nervosa 804
T egretol see carbamazepine
telencephalon 156–7
telephone helplines 975, 1282, 1708, 1805–6
telephone scatalogia 833, 1961
T elephone Search 88, 89
telomerase 1508
telomeres 223
loss with age 1508
temazepam 1179
as a hypnotic 1183
misuse 430, 491, 1179, 1183
temperament 79assessment 79–80, 80, 680

clinical 82–3
in childhood and adolescence 235, 238, 238,
1601, 1665, 1667
dimensions 79–80, 
80, 316, 316
hyperthymic 690–1
and mood disorders 654, 658, 680
and personality 316, 316
T emperament and Character Inventory 79, 80,
81, 81,858
temperature regulation, in anorexia 
nervosa 785
temporal difference learning 259
T emporal Judgement T est 90
temporal lobes
anatomy 146, 147, 148
temporoparietal junction 245
TEMPS-A 680
T enancy Sustainment Programme 1501
teratology, neurobehavioural 1614
TERM model 1005, 1008, 1008
adjustment to 1069–70
in childhood and adolescence 1743–4
terrorism 1987T est of Everyday Attention 89

T est of Malingered Memory see T oMM
testosterone 815, 834
interventions to reduce levels 838
reduced levels 826
replacement therapy 828
therapy in gender identity disorder 843
testosterone antagonists in adolescents with 
T ests of Everyday Attention for Children 1647
tetrabenazine in Huntington’s disease 374
tetracyclic antidepressants
tetracycline transactivator system 230, 231
δ-9-tetrahydrocannabinol 172, 507
TF-CBT (trauma-focused cognitive-behaviour 
therapy) 708, 1109, 1111, 1730
TFP (transference-focused psychotherapy) 304, 
318–19, 894, 895, 904
TGA (transient global amnesia) 59, 403
thalamus
in alcohol use disorders 183, 400, 406
cortical projections 150, Plate 2
development 158

thalamus
infarction 407and memory 254
in neuroﬁ  bromatosis 1844
THC ( δ-9-tetrahydrocannabinol) 172, 507
theft 1941–3
management 1942
motivational classiﬁ  cation 1941–2
prevalence 1941shoplifting 1943
types of 1941see also  kleptomania
Theory of Reasoned Action/Theory of Planned 
Behaviour 1137, 1140
therapeutic alliance 299
in brief psychodynamic psychotherapy 1328
in cognitive-behaviour therapy 903, 1307in counselling 1275importance of 317
therapeutic communities 1391–8
addiction 1391
background 1392–3
in childhood and adolescence 1397
core standards 1392, 1392
culture of enquiry 1393deﬁ nitions 1392
in ﬁ rst episode psychosis 1396
indications and contraindications 1394, 1395

in intellectual disability 1397
living–learning situation 1393
for offenders 1396
pathways and process 1394–5
in personality disorders 892, 896, 905, 1395–6
principles (themes) 1392
research evidence 1395–7
in severe and enduring mental 
disorder 1396–7
staff and client roles 1394
staff training 1393–4
in substance use disorders 1396
technique 1393
therapeutic index 431therapist
in family therapy 1386–7
in group therapy 1354, 1354
neutrality 1339, 1340
theta rhythm 203thiamine
deﬁ ciency
in alcohol use disorders 405, 408–9, 444–5
supplementation in alcohol withdrawal 450
thinking
abstract 53
acceleration of 53concrete 53
control of 53
disorders of 50–4
fantasy/dereistic/autistic 50
ﬂ ow of 52–3
imaginative 50
incoherent 53
in mood disorders 52
negative 52

thinking
ﬂ ow of 52–3
overinclusive 53rational/conceptual 50
retardation of 53
types of 50
thiopentone 1178
thioridazine 1209
adverse effects 1212 , 1222, 1532
pharmacology 1210
thiothixene 1209
third sector see voluntary organizations

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022third sex 844
Thorn Initiative 1405
thought-action fusion in obsessive–compulsive 
thought blocking 53
thought broadcast 527
thought content, elderly people 1527
Thought Disorder Index 528
thought disorders
differential diagnosis 538
in schizophrenia 527, 573
thought insertion 527
Thought, Language and Communication 
Scale 528
thought process abnormalities in delirium 326
thought stopping
in insomnia 936–7
in obsessive–compulsive disorder 770
thought withdrawal 527
threat-control override 1919
thymine 223
thyroid
function
and suicide 966
tumours 1101
thyroid-stimulating hormone 163, 966, 1204
thyrotrophin, in depression 661thyrotrophin-releasing hormone 163, 171,
706, 966
thyroxine 163, 1101
tiagabine 1237, 1867
tianeptine 1186tiapride 1688
tic disorders
childhood and adolescence 1073, 1680–93
clinical features 1681

chronic motor 1682
chronic vocal 1682
genetics 229, 1073, 1684
and obsessive–compulsive disorder 765, 
1073, 1681
secondary 1073
transient 1073, 1682
see also  T ourette syndrome
tics 58, 58, 1681
complex motor 1681
complex verbal 1681
motor 1073, 1681
phonic 1073
secondary 1683stimulant-induced 1651
vocal 1681
time-limited psychotherapy 1327, 1332–3
time out on the spot 414
time sampling 97
timetabled tasks 1376–7tina (methamphetamine) 497–8tinnitus, chronic 1265
TMS see transcranial magnetic stimulation
TNF- α (tumour necrosis factor- α) 209
tobacco see smoking
tocophobia 1117, 1121
T oken T est 89
tolerance 427, 428

‘tomboyism’ 1719T oMM 1057
TOOTS (time out on the spot) 414
topiramate (T opamax) 1236–7
adverse effects 1236
dosage and administration 1237
drug interactions 1236–7
in epilepsy 1080indications and contraindications 1236
overdose 1236
pharmacokinetics 1236, 1867
pharmacology 1236
in pregnancy 1236
withdrawal 1237
torture
of refugees 1494, 1495
of women 1498
torulosis 1093
T ourette syndrome 1073–4
aetiology 1073
differential diagnosis 1644
epidemiology 1073
genetics 229, 1073, 1684with intellectual disability 1851
and obsessive–compulsive disorder 765, 1073
psychiatric comorbidity 1073and sleep-wake disorders 932, 1697
treatment and management 1073–4
see also  tic disorders
T ower of London task 255, 265

toxoplasmosis 1863
in HIV/AIDS 1093
maternal, and schizophrenia 548
toys, in child and adolescent assessment 1604
TPQ see T emperament and Character 
Inventory; Tridimensional Personality Questionnaire
traditional healers 15
and diagnosis 65
use by refugees 1497
Trail Making T est 90, 326
Trailblazers 1487–8
training
approved social workers 1410
in child and adolescent psychotherapy/
counselling 1768–9
in cognitive-behaviour therapy 1312
community psychiatric nurses 1405
in consultation-liaison psychiatry 1147
in counselling 1282–3
in couple therapy 1379in family therapy 1389–90
in interpersonal psychotherapy 1325
primary care workers 1487–8
in psychoanalysis 1346
staff in therapeutic communities 1393–4staff working with adults with

staff in therapeutic communities 1393–4staff working with adults with 
psychiatric disorder and intellectual disability 1889–90trance 276
trance-based healing systems 1418–19
tranquillizers see anxiolytics
transactional analysis 1277
transcranial magnetic stimulation (TMS/rTMS) 
671, 1258, 1263–6
adverse effects 1263
in chronic neuropathic pain 1265
in chronic tinnitus 1265
comparison with ECT 1264–5
in depression 1264
mechanism of action 1263
in obsessive–compulsive disorder 1265
in Parkinson’s disease 1265
in post-stroke depression 1555
in schizophrenia 1265
sham treatment 1264
technique 1263–4
transcription factors 224
clinical relevance 13–14
and epidemiology 14
and social anthropology 15
transference 297–8, 298–9, 300, 1338, 1342–3
bidimensional quality 314
in brief psychodynamic 
psychotherapy 1328–9, 1330
in childhood psychodynamic

in childhood psychodynamic 
psychotherapy 1765, 1772
dimensions 1343
eroticized 1343idealizing 1343
mirroring 1343
object-relations theory model 298–9
and play 1770and psychodynamic psychiatry 314
and resistance 315
reverse 1343
transference-focused psychotherapy 304, 
transformation 294
transgenic animals 230
transient global amnesia 59, 403
transient ischaemic attacks 364, 403
transitional objects 309, 1603, 1694
in pharmacotherapy 317
transitional space 1770
transketolase 408
transmission disequilibrium test 220, 220
transorbital lobotomy 1267transplantation surgery 456, 1087, 1097
transsexualism see gender identity disorder
transtheoretical model 1137
transvestic fetishism 832, 833, 834, 836, 837, 844
tranylcypromine 670, 670

limitations on use 1188
trauma
associated with post-traumatic stress 
disorder 704
in childhood and adolescence 1601, 1697, 
1728–31 , 1744, 1762

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022trauma ( cont.)
counselling following 1279–80
creeping 1903
debrieﬁ  ng 1497
group therapy with victims 1365
nature of memories of 705–6
personal meanings of events 705
prevalence 704
to refugees 1494–6, 1495 , 1496–7, 1497
story 1497
see also  accidents
trauma-focused cognitive-behaviour 
therapy 708, 1109, 1111, 1730
traumatic bonding 1982
trazodone 670, 671
in anxiety disorders 1182in cancer 1103
as sedative 1194
treatment
adherence to 1140
behaviour 1140–2
cultural variations in 1442–3
ethical issues 29–30
evaluation 141–2
physical treatment 1151–8
psychotherapy 1158–67
involuntary/compulsory 30, 1053–4
manuals 1161
determinants 1140–1
and estimation of efﬁ  cacy 142
incidence 1140
intentional/unintentional 1140

psychodynamic approaches to 317
refusal
advance directives 1577
right to 29–30, 1565
in surgery 1096–7
right to effective 29
right to 29
as security 2017
treatment foster care, in conduct disorder 1662
treatment gap 12, 13
Treatment Outcomes Proﬁ  le 519, 519
Treatment Services Review 1165
tremor
in alcohol withdrawal 438–9
in HIV-associated dementia 384lithium-induced 1204
Treponema pallidum  1447
TRH (thyrotrophin-releasing hormone) 163, 
171, 706, 966
triangular model 310
triazolam 1169
trichobezoars 915
trichotillomania 618, 915–16
tricyclic antidepressants 669–70, 670
in adjustment disorders 1068
adverse effects 674, 1188, 1191delirium 1532
hypersomnia 939
postural hypotension 1529

sexual dysfunction 826–7
in childhood and adolescence 1676, 1796
drug interactions 1194
slow metabolisers/slow hydroxylation 1188
suicide risk 674, 1707
Tridimensional Personality Questionnaire 
654, 851, 887
triﬂ uoperazine 1209
pharmacokinetics 50
trihexylphenidyl 1225
triiodothyronine 163, 675, 784
Trileptal see oxcarbazepine

trimethoprim-sulphamethoxazole 1091
trimipramine 670,1187 ,1189 ,1191 ,1196
Triple P programme 1791
trisomy 228
trisomy 21 see Down syndrome
Trk (tyrosine kinase) receptors 159
true score ( t) 85, 92
trypanosomiasis 942
tryptamine 500–1
tryptophan 662, 1248tryptophan hydroxylase (TPH1) gene 652
TSH (thyroid-stimulating hormone) 
163, 966, 1204
tTA system (tetracycline transactivator 
system) 230, 231
tuberculosis 1094
tuberous sclerosis
and autism 1075, 1635
behavioural and psychiatric aspects 1075, 
1846, 1852
genetics 1075, 1845, 1866
physical characteristics 1846, 1850
‘Tuesday blues’ 496
Tuke, William 17
tumour necrosis factor- α 209
Turkey, attitudes to psychiatric disorder 6

behavioural and psychiatric aspects 1840–1
genetics 224, 1840
mouse model 225
12-step programmes 451–2, 452, 477, 477
twilight states 60, 1531twin similarity questionnaire 216
twin studies 215–16
anxiety disorders 1667attention-deﬁ  cit hyperactivity disorder 1646
chronic fatigue syndrome 1039
depression 649
longevity 1507
mood disorders 651
schizophrenia 554
social anxiety disorder 741speciﬁ  c phobia 745
two-by-two table 280, 280
tyrosine kinase receptors 159
ubiquitin
in frontotemporal dementias 344
in Lewy bodies 362, 369
ulcerative colitis 1083–4
unconscious
dynamic 294

ubiquitin
and the ego 295Freudian theory of 293–4
and the id 294–5
in psychodynamic psychiatry 313–14
unconscious phantasy 307
uncus 146UNHCR (United Nations High Commission for 
Refugees) 1493
Uniﬁ  ed PD Rating Scale 363
United Kingdom
cost of psychiatric disorder 11
national prevalence study of psychiatric 
disorder in childhood and 
adolescence 1595–6
neurasthenia as diagnostic entity 1061
United Nations
Convention against T orture and Other Cruel 
Inhuman or Degrading Treatment or 
Punishment 1494
Convention on the Rights of the Child 1731
Convention on the Rights of Persons with 
Disabilities 1896–7
Declaration of Human Rights 1427, 1494
Declaration on the Rights of Mentally 
Retarded Persons 1819, 1895–6
High Commission for Refugees 1493
MI principles 1427
United States
art therapy 1414

child abuse legislation 1732
group therapy 1353–4
neurasthenia as diagnostic entity 1060, 1061
United States–United Kingdom Diagnostic 
Project 71
universe score 92Unverricht–Lundborg disease 
1864, 1866 , 1868
uracil 223
urbanization 1728
urinary incontinence
in dementia 417

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022following neurosurgery for mental 
urocortin 661
urophilia 833
utility, measurement of 1475
utilization behaviour in frontotemporal 
utilization delay 1137
VaD see dementia, vascular
vagina 818, 822vaginismus 823vagus nerve stimulation 671, 1258, 1269
Valeriana ofﬁ  cinalis  (valerian) 1248, 1249, 1250
validation therapy in dementia 414
validity 85, 92, 95
of assessment instruments 140–1, 284in classiﬁ  cation in childhood and 
adolescence 1590–1
concurrent 86
construct 86
content 86
discriminant 859
face 86
factorial 86
incremental 86
internal vs. external 1159
of outcome measures 1465
predictive 86
of randomized controlled trials 127–8
of systematic reviews 126
types 86
valproate 1198, 1200, 1231–3
adverse effects 1169, 1200 , 1204, 1232
in bipolar disorder 671, 672, 677, 1556
in childhood and adolescence 1798choice of 1866

dosage and administration 1233, 1233
drug interactions 1175, 1205, 1232–3, 1866indications and contraindications 1232
monitoring therapy 1176overdose 1232
pharmacokinetics 1203, 1232, 1867
pharmacology 1201, 1202 ,1203 , 1231–2
in pregnancy and breast feeding 
1118, 1169, 1232
withdrawal 1206–7, 1233
valpromide 1231
value learning 259
values 32–8
ethical 32–3
in the multi-disciplinary team 33–5, 34
values-based practice 32–8
and evidence-based medicine 33
key points 37
key skills areas 33
in the multi-disciplinary team 
34, 35, 36
values statement 43
Valuing People  1819, 1878, 1879
vardenaﬁ  l 828
varenicline 513vasopressin 815

34, 35, 36
and aggressiveness 889
vCJD see Creutzfeldt–Jakob disease, variant
velo-cardio-facial syndrome
1826, 1846
genetics 1846
physical characteristics 1846
prevalence 1846
veneroneurosis 1094
venlafaxine 670, 670
drug interactions 1176
ventilators, weaning from 1099
ventral anterior nucleus 150
ventral horn 157
ventral lateral nucleus 150ventral parieto-frontal network 245
ventral root 157
ventricular dysrhythmias 1081
ventricular zone 157

ventriculomegaly 388verapamil 1200–1, 1201, 1205, 1206
verbal ﬂ  uency tests 264
verbal recall 264
verbigeration 54, 58, 58
very-late-onset schizophrenia-like 
psychosis 1518–19
vesicular monoamine transporters 170, 170
Viagra® (sildenaﬁ  l) 821, 828
victims
of burglary/robbery 1986in childhood and adolescence 1986–7
empathy with 2000
of hate crimes 1987
impact of criminal victimization 1984–90
immediate and short-term effects 1984–5
long-term effects 1985
primary 1902of rape/sexual assault 1985–6
secondary 1902–3, 1985
support groups 1986, 1987, 1988
of terrorism 1987
treatment 1987–8of workplace violence 1986
video replay techniques, psychological 1109
video-telemetry, in epilepsy 1078
vigabatrin
adverse effects 1079in epilepsy 1080
vigilance 59, 247, 264

Vineland Adaptive Behaviour Scales 1821
violence
and alcohol consumption 1926
in alcohol use disorders 453and body dysmorphic disorder 1044and delusional disorder/delusions 1920, 1929
domestic 1449, 1981–3
gender-based 1495, 1498
homophobic 1987in inpatient settings 1404
and mental disorder 1937
and offending 1918, 2010–11
prevention 1449
racially-motivated 1987
to refugees 1494–6, 1495
risk assessment and management 1991–2002
and schizophrenia 1919, 1995, 1999
situational factors 1914
and stalking 1973–4, 1998
and substance use disorders 1449, 1926, 1999
in the workplace 1986
see also  aggression
Violence Risk Appraisal Guide 835, 1994, 1996, 
1997, 1998
viral infection

1997, 1998
risk of in opioid use 475
Virchow, Rudolph 276
vision
cortical association pathways 147, 152
dysfunction in conversion disorder 1017
impairment following head injury 391
vision statement 43
visual backward masking paradigm 259Visual Object and Space Perception Battery 264
visual search paradigm 246–7
vitamin A, teratogenic effects 1614
vitamin B1 deﬁ  ciency
in alcohol use disorders 405, 408–9, 444–5in anorexia nervosa 785
vitamin B12 deﬁ  ciency 1087–8
vitamin E
in tardive dyskinesia 1249
‘vitamin K’ (ketamine) 489, 499–500 , 1186
VMAT (vesicular monoamine 
transporters) 170, 170
VNS (vagus nerve stimulation) 
671, 1258, 1269
vocabulary, problems with 1711
vocational training/rehabilitation 1400–1

in schizophrenia 583
volatile substance abuse (VSA) 502–6
cognitive effects 92–3
health issues 504
mortality associated 503–4, 504
in pregnancy 504
prevalence 503
prevention 505–6
product range 503
treatment 504–5
volition 1012
disorders in schizophrenia 530
voluntarism 29
voluntary organizations
and community mental health 
services 1460
counselling by 1279, 1281
role of 1490–2

index
VOLUME 1  PP .1–986   VOLUME 2  PP .987–2022vomiting
in anorexia nervosa 782–3, 784, 794
in bulimia nervosa 802–3
voodoo death 981
voyeurism 832, 833,836, 1960, 1961
VRAG (Violence Risk Appraisal Guide) 835, 
1994, 1996, 1997, 1998
VRE (virtual reality exposure) 746
VSA see volatile substance abuse
vulvar vestibulitis syndrome (VVS) 823
WAIS-IIIUK (Wechsler Adult Intelligence Scale-
Third Edition UK Version) 87, 88, 89, 264
wandering in dementia 415
warfarin
adverse effects 1532
drug interactions 1174, 1233
waxy ﬂ  exibility 58, 58
Wechsler Adult Intelligence Scale - Third 
Edition UK Version 87, 88, 89, 264
Wechsler Intelligence Scale for Children - IV 
UK Version 87, 88
Wechsler Memory Scale - Third Edition 89, 89,
253, 255, 264
Wechsler Objective Reading Dimensions 
T est 89
Wechsler Preschool and Primary Scale of 
Intelligence - Revised 87
Wechsler Scale for IQ 1821
Wechsler T est of Adult Reading 264
Weekly Activity Schedule 1307–8, 1308
weight gain

T est 89
in antipsychotic therapy 1223following neurosurgery for mental 
following weight loss 1084
weight loss 1084
Wernicke–Korsakoff syndrome 59, 92, 
399–402 , 405–6, 408–9, 444–5, 785
memory impairment 252
neuropathology 182–3
prevention 450, 1542
Wernicke’s area 153, 153
Wernicke’s dysphasia 1527
West syndrome 1862, 1863
Western Aphasia Battery 89
WFSAD (World Fellowship for Schizophrenia 
and Applied Disorders) 1491
‘what if’ syndrome 751
wheel of change 451
whiplash injury and whiplash-associated 
disorder 1002, 1056, 1108
Whiteley Index 1023
whizz see amphetamine
WHO see World Health Organization
WHO/PIRS (Psychological Impairments Rating 
Scale) 72whole-person medicine 66
widowhood 1513wild yam 1249
behavioural phenotype 1613, 1614, 1846,

behavioural phenotype 1613, 1614, 1846, 
1851 , 1858
psychiatric aspects 1846
Willis, Thomas 630, 631
Wilson’s disease 537, 1084
Winnicott, Donald 309, 313, 1770
WISC-IV
UK (Wechsler Intelligence Scale for 
Children - IV UK Version) 87, 88
Wisconsin Card Sort test 248, 249, 255, 265, 
266, 563
Wisconsin Personality Disorders Inventory 
(WISPI) 858, 858
withdrawal 427
schizoid 308
witnesses
children as 1761–3
expert see expert witness
WMT (Word Memory T est) 1057
Wnt (wingless) gene 156
Wolf, Alexander 1354
women
alcohol use disorders 454–5, 464
torture 1498
word-blindness, pure 54
word-deafness, pure 54word-dumbness, pure 54
Word Memory T est 1057
word salad 54
working through 299, 1340
workplace
counselling services 1281–2
violence 1986

workplace
World Development Report: investing in 
health  10
World Fellowship for Schizophrenia and 
Applied Disorders 1491
World Health Organization (WHO)
CHOICE project 1477
Division (Section) of Mental Health 23
Health for All 969and mental health public policy 1427
World Health Report 2001  10, 12, 
1427, 1606
World Mental Health Survey 645World Psychiatric Association 23
WPPSI-III (Wechsler Preschool and Primary 
Scale of Intelligence - Revised) 87
wrist actigraphy 934, 1697
WTAR (Wechsler T est of Adult Reading) 264X chromosome 223
females with single 225
inactivation 224
X-linked intellectual disability (X-linked mental 
retardation) 1831–2, 1839–40, 1842
xanomeline 1241
behavioural and psychiatric aspects 1841
genetics 1841

genetics 1841physical characteristics 1841
yaba (methamphetamine) 497–8
Y ale-Brown Obsessive-Compulsive Scale 1163
Y alom, Irving 1354, 1355
yaun  983
yearning 725
Yi-Jing  1420
yohimbine 706, 754, 828
Y oung Mania Rating Scale 1164, 1675
Y oung Offenders Institutions 1945
Y outh Justice System 1945, 1947
Y outh Offending T eams 1945
zalcitabine 1091
zaleplon 1102 , 1178, 1179, 1183
zar ceremonies 1419
zeitgebers  1260, 1261
zidovudine 1091 , 1092
zimelidine 409
ziprasidone 1199, 1209, 1209 , 1797
administration 1214 , 1218–19
, 1224
ZKPQ (Zuckerman–Kuhlman Personality 
Questionnaire) 81, 81

, 1224
zolmitriptan 1171zolpidem 1178, 1179, 1182–3
zonisamide (Zonegran) 1198, 1237
Zoo Map T est 90
zopiclone 1171, 1178, 1179, 1182–3
zotepine 1209
Zuckerman–Kuhlman Personality 
Questionnaire 81, 81
zuclopenthixol 1172
Zung’s Self-Rating Anxiety Scale 717
Zung’s Self-Rating Depression Scale 717

Plate 2 (a) The thalamus is shown as if removed from the brain at the top, with the individual major nuclei indicated. (b) Schematic di agram showing the isolated 
thalamus divided approximately at the middle of its anteroposterior extent; the arrows indicate known sources of major subcorti cal afferents to the individual named 
nuclei. (c) The diagram of the isolated thalamus shown in (a) with the individual main nuclei colour coded. (d), (e) Schematic diagrams of the cerebral surfaces (medial 
and lateral) showing the regions of cortex colour coded to correspond to the main thalamic nuclei with which they have major co nnections.
Plate 1 (a) Laminar structure of the cerebral neocortex; (b) excitatory amino acid using spiny neurones of the neocortex.Plates for Chapter 2.3.1

Plate 3 Steps in the production and use of PET radio-isotopes.
Plate 4 Principles of positron emission: β– is an electron and β+ is a positron. 
Two high-energy gamma rays ( γ) are produced on annihilation of a positron by an 
electronPlate 6 Steps in the data analysis of a PET radiotracer.
Plate 5 Use of a PET radiotracer to image 5-HT1A receptors in the human brain.
Plate 7 Spin echo MR images and artefacts. Top row, spin echo images: left, proton 
density image (TR = 2000 ms, TE = 20 ms); middle, T1-weighted image (TR = 350 ms, 
TE = 20 ms); right, T2-weighted image (TR = 2000 ms, TE = 90 ms). The arrow on 
the T2-weighted image indicates blurring caused by movement (swallowing) during

the T2-weighted image indicates blurring caused by movement (swallowing) during 
acquisition. Bottom row, examples of poor tissue contrast and susceptibility artefact: left, spin echo image showing poor contrast due to injudicious prescription of pulse sequence (TR = 350 ms, TE = 90 ms); middle, bulk susceptibility artefact; right, ferromagnetic susceptibility artefact caused by a metallic hairgrip.
Plate 8 Diffusion-weighted MRI data can be used to generate maps of (left) 
the apparent diffusion coefﬁ  cient ( ADC ) and (right) the anisotropy of diffusion. 
Diffusion of protons is most rapid and isotropic in cerebrospinal ﬂ  uid, and least rapid and most anisotropic in white matter. White matter is clearly deﬁ  ned by relative h
yperintensit y in the anisotro py map.
Plates for Chapter 2.3.6
Plates for Chapter 2.3.7

Plate 9 Steps in computerized image analysis. Dual-echo (fast spin echo) data 
are acquired from several cases and controls in a cross-sectionally designed study. 
Extracerebral tissue is removed (1) from each image before segmentation or tissue 
classiﬁ  cation (2). Tissue-calssiﬁ  ed images are registered with a template image in 
standard space (3) before hypothesis testing (4). Voxels or clusters, which demonstrate 
a signiﬁ  cant difference in tissue class volume between groups, are colour coded.
Plate 10 Steps in computerized data analysis. Gradient echoplanar imaging data 
have been acquired from three subjects under identical conditions. The time series 
at each voxel is analysed to estimate a measure or parameter of the experimental 
effect, which is represented as a parameter map. Signiﬁ  cantly activated voxels 
or clusters can be identiﬁ  ed in each individual image. Parameter maps can be 
averaged over individuals and generically activated voxels or clusters identiﬁ  ed

averaged over individuals and generically activated voxels or clusters identiﬁ  ed 
over the group of subjects. The power to detect activation is enhanced by 
cluster -level analysis and by combining data from several subjects.
Plate 11 Activation map. Generically activated voxels are colour coded against a 
grey-scale background of gradient echoplanar imaging data. The grid respresents the 
standard Talairach-Tournoux Space;12 z-coordinates for each slice are shown at the 
bottom left. Colour codes the timing and power of a periodic response to a covert 
verbal-ﬂ  uency experiment. Blue voxels show increased magnetic responance signal 
during condition B (repeat a word covertly); light blue represents a greater power 
of response than dark blue. Red voxels show increased magnetic resonance signal 
during condition. A (generate a word beginning with a cue letter); yellow and orange

during condition. A (generate a word beginning with a cue letter); yellow and orange 
represent a greater power of response than dark red. The voxel-wise probability of 
a false-positive error is p = 0.0001. The main areas activated during conditioin A are 
the dorsolateral prefrontal cortex, inferior frontal gyrus, and supplementary motor 
area; the main areas activated during condition B are the medial parietal cortex and 
posterior cingulate gyrus.
Plate 12 Regional cerebral blood ﬂ  ow (rCBF) measured using SPECT with 
exametazine (left) and the Xenon-133 inhalation method (right) in a 54-year-old 
female with clinical signs of FTD. The variation of regional cerebral blood ﬂ  ow is 
measured with xenon-133, above (red) or below (green) the average ﬂ  ow level, 
as indicated by the colour code. The patient showed the ﬁ  rst signs of personality

as indicated by the colour code. The patient showed the ﬁ  rst signs of personality 
change, and stereotypy of speech and behaviour at the age of 48 years. EEG was 
normal, and CT and MRI showed slight frontal cortical atrophy. The regional 
cerebral blood ﬂ  ow measurement with xenon-133 showed a normal average 
ﬂ  ow level and marked bilateral, frontal ﬂ  ow decreases. The SPECT scan showed a 
severe perfusion deﬁ  cit in the frontal and anterior cingulate cortex. (Courtesy of 
Department of Neurophysiology, University Hopital, Lund, Sweden.)
Plates for Chapter 2.3.7 (continued)
Plates for Chapter 2.3.8Plate for Chapter 4.1.3

Plate 13 Area of activation during opiate craving: (a) [15O]H2O PET SPM image; 
(b) area of activation superimposed on magnetic resonance image.
Plate 14 Statistical parametric maps (p < 0.001) for reductions in grey matter 
densities in subjects with chronic refractory depression compared with controls. Effects are controlled for age. (Reproduced with permission from P .J. Shah et al. (1998). 
Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression: controlled MRI study. British Journal of Psychiatry , 72, 527–32.)
Plate 15 Typical locations of anterior capsulotomy lesions superimposed upon 
normalized T1 MRI scan. Lesions not to scale.
Plate 16 Typical locations of anterior cingulotomy lesions superimposed upon 
Plate for Chapter 4.2.1
Plate for Chapter 4.5.6Plates for Chapter 6.2.10.4